Targeted Genome Editor Delivery (TARGETED) Challenge | National Institutes of Health (NIH)

Skip to main content Official websites use .gov A .gov website belongs to an official government organization in the United States. Secure .gov websites use HTTPS A lock () or https:// means you’ve safely connected to the .gov website. Share sensitive information only on official, secure websites. Breadcrumb Targeted Genome Editor Delivery (TARGETED) Challenge Targeted Genome Editor Delivery (TARGETED) ChallengeRevolutionizing technology development of delivery systems for in vivo genome editing. Image A $6,000,000 competition to improve in vivo delivery technologies for genome editors in two Target Areas: 1. Programmable delivery systems, and 2. Non-viral delivery across the blood-brain barrier. Phase 3 open until 05/04/26 05:00 PM EDT Total cash prizes:$6,000,000 Submit on External Website Overview Subject of the Challenge: Recent advancements in the genome editing technology field have enabled scientists to manipulate genomic sequences rapidly and efficiently. Despite revolutionary progress in this area, several challenges remain. Existing gene editing technologies like CRISPR-cas9, base editors and prime editors have great potential, but existing delivery technologies are not able to deliver gene editing technologies to many target tissues and cell types in sufficient quantities, which hinders clinical applications. While some cell types, like hepatocytes in the liver, have many delivery technologies capable of delivering genome editors, there are many other organs and cell types that are harder to reach. The Targeted Genome Editor Delivery (TARGETED) Challenge is a $6,000,000 challenge to improve the current state of in vivo delivery technologies for genome editors in two Target Areas: 1. Programmable Delivery System for Gene Editing, and 2. Crossing the Blood-Brain Barrier. The National Institutes of Health (NIH), through the Common Fund’s Somatic Cell Genome Editing (SCGE) program, is seeking Participants with ideas or early-stage solutions to join the Challenge with the chance to win up to $1,000,000 and have their solution independently tested and validated in large animal models through NIH-supported independent evaluation relevant to preclinical assessments of investigational products. The Challenge is a three-phase competition. In Phase 1, Participants will be asked to submit a proposal describing their proposed solution and how it will address the requirements for one of the Target Areas. Participants may submit proposed solutions to both Target Areas but must do so with separate proposals that independently address each Target Area’s requirements. Up to ten proposals that are judged to best meet the requirements will each be awarded up to $75,000. Additional prizes of $50,000 may be awarded to additional meritorious solutions on the basis of the Judging Criteria. In Phase 2, Participants must submit data from studies that demonstrate delivery and editing performance as well as describe their methodology, technology, and how their solution addresses the Challenge criteria. Participation in Phase 1 is not a requirement for participation in Phase 2; however, it is strongly encouraged. Up to 10 winners of Phase 2 will be each awarded $250,000 and will be eligible to compete in Phase 3. Only Phase 2 winners will be eligible to participate in Phase 3. Phase 3 is separated into Phase 3a and 3b; all Participants must submit solutions for Phase 3a to be eligible to participate in Phase 3b. For Phase 3a, Participants must submit all required information showing that their technology is ready for large animal testing through NIH-supported independent evaluation and has the ability to solve the requirements for one of the Target Areas. Up to 6 Participants will each be awarded $50,000 and will then prepare for reagent scale up and protocol development for NIH-supported large animal testing. Participants who submit their reagents and protocols by the deadline for Phase 3b will have access to NIH-funded independent large animal testing to validate their solution. NIH will review the results and only award prizes to Participants whose solutions meet or exceed the criteria. The top successful solution in each Target Area will be awarded $625,000; the second place solution in each Target Area will be awarded $225,000; the third place solution in each Target Area will be publicly recognized and given an honorable mention award. Participants who participate successfully in all three phases could be awarded up to $1,000,000 in each Target Area. Final (Phase 3) Solution Requirements Target Area 1: Programmable Delivery System for Gene Editing Solutions must be a highly efficient and programmable delivery system to deliver genome editing machinery that can target specific tissues (cells, types, and/or organs). Solutions must be able to be programmed to deliver to at least three distinct and different cell(s), tissue types, and/or organs and with delivery and editing capability that is at least as efficient as the current state of the art. An optimal solution would be straightforward to manufacture, low-cost, scalable and have a reasonable safety profile. Solutions that propose viruses and viral-like systems or particles must build on the field and meet the criteria demonstrating full understanding of how the delivery system can be modified so that it is programmable and can target a variety of different tissue targets (cells, types, and/or organs). The solution will be judged on how well it meets the criteria. Programmable solutions that only target central nervous system (CNS) targets should be submitted under Target Area 2. Solutions that meet the requirements for Target Area 2 but also are programmable to target a non-brain organ may be submitted for consideration in both Target Areas, though a single team and/or entity with a single solution that meets the requirements of both Target Areas are only eligible for one prize. A team and/or entity may be eligible for multiple prizes for multiple solutions submitted to either or both Target Areas, as long as the solutions are qualitatively different. To be highly competitive in this Challenge, solutions must: Be programmable and target at least three distinct and different cell(s), tissue types, and/or organs. Be able to deliver an editor and demonstrate delivery and editing that be at least as efficient as the current published efficiencies for the different tissue targets (cells, types, and/or organs) proposed. Have a known biological mechanism for programmability: a clear relationship between what is done to modify the technology to deliver to different tissue targets (cells, types, and/or organs) and how this relates to the underlying biology and/or biochemistry of the system. Have conducted studies that demonstrate biodistribution and route of administration/delivery method. Demonstrate successful delivery and editing performance in large animals through NIH-supported independent evaluation. Have demonstrated a safety profile in experimental models consistent with other gene therapy/gene editing delivery systems intended for use in humans. Solutions should also have these desired traits: Target more than one tissue/organ type. Be innovative in approach. Additionally, solutions could: Demonstrate market potential, competitive advantage, or potential to meet unmet medical needs. Be able to be manufactured in a scalable and cost-effective manner. Target Area 2: Crossing the Blood-Brain Barrier (BBB) Solutions to Target Area 2 must be highly efficient, non-viral delivery systems capable of crossing the BBB to deliver genome editing machinery to a substantial proportion of clinically relevant cell types in the brain. To be highly competitive in this Challenge, solutions must: Be able to traverse the BBB in vivo. Be able to deliver an editor and demonstrate delivery and editing in a substantial proportion of clinically relevant cell types in the brain. Be a non-viral delivery technology. Solutions may be virus-like particles and/or incorporate components of viruses in the proposed delivery technology. Solutions that are modifications of recombinant adeno-associated viral vectors do not meet this criterion. Demonstrate successful delivery and editing performance in large animals through NIH-supported independent evaluation. Have demonstrated a safety profile in experimental models consistent with other gene therapy/gene editing delivery systems intended for use in humans. Solutions should also have these desired traits: Be innovative in approach. Be able to be manufactured, ideally synthetically, in a scalable and cost-effective manner. IP Considerations: Through the TARGETED Challenge, NIH aims to maximize public access to the winning delivery technology solutions (as defined as the delivery vehicle for the genome editing machinery), and to maximize the number of people who can benefit from therapeutic genome editing utilizing the winning delivery technologies, regardless of the prevalence of their disease. To balance these objectives with encouraging appropriate licensing and commercialization of the technology, the NIH is requiring the inclusion of a Public Access and Dissemination Plan (PADP) as part of the submission. Instructions for how to prepare this are given in the “How to Enter” section. Partners: The SCGE program is led by the NIH Common Fund, the National Center for Advancing Translational Sciences (NCATS), and the National Institute of Neurological Disorders and Stroke (NINDS). The Brain Research Through Advancing Innovative Neurotechnologies (BRAIN) Initiative and the National Heart, Lung, and Blood Institute (NHLBI) are also contributors to this Challenge. Challenge Administration: This Challenge is administered and managed with support from Freelancer.com under a contract awarded by the National Aeronautics and Space Administration (NASA) Center of Excellence for Collaborative Innovation on behalf of NIH. Statutory Authority to Conduct the Challenge The NIH Common Fund is a component of the NIH budget which is managed by the Office of Strategic Coordination, Division of Program Coordination, Planning, and Strategic Coordination, Office of the Director. Common Fund programs address emerging scientific opportunities and pressing challenges in biomedical research that no single NIH Institute or Center (IC) can address on its own but are of high priority for the NIH as a whole [42 U.S.C. 282a(c)(1)]. The SCGE program is supported by the NIH Common Fund to improve the efficacy and specificity of gene editing approaches, and to accelerate the clinical development of genome editing. The NIH Office of the Director is conducting this Challenge under the America Creating Opportunities to Meaningfully Promote Excellence in Technology, Education, and Science (COMPETES) Reauthorization Act of 2010, as amended [15 U.S.C. § 3719]. This Challenge is consistent with and promotes the agency’s mission by catalyzing the goal-driven development of innovative tools and technologies with the potential to enhance human health. Supplementary Information: The TARGETED Challenge is a continuation of NIH’s Common Fund’s Somatic Cell Genome Editing (SCGE) program. The SCGE program aims to improve the efficacy and specificity of gene editing approaches to help reduce the burden of common and rare diseases caused by genetic changes. Thousands of debilitating diseases can be attributed to genetic mutations, such as Huntington’s Disease, cystic fibrosis, and Duchenne Muscular Dystrophy. In order to treat a disease, a significant number of genome editors must be delivered to the disease-relevant cell type. Getting gene editing tools into sufficient numbers of cells, in the diverse organs associated with different diseases, requires improved delivery technologies. Even in cases where targeted delivery to the desired tissue or cell type is achieved, the efficiency rate—the percentage of cells that are ultimately edited —is typically less than ideal. Gene editing as a means of treating diseases is an exciting but challenging prospect. In order to realize the full potential of genome editing, there must be transformative advances in the two strategic Target Areas. Current State of Research Target Area 1: The discovery of CRISPR genome editing technology has greatly enhanced the potential to treat diseases. However, delivering genome editing components safely and effectively has proven to be challenging. The current lack of specific programmability is a key limiting factor for successfully scaling this technology. A variety of delivery approaches, including but not limited to those below, could potentially meet the need to target tissues and/or cells to advance these technologies into the clinic. To date, lipid nanoparticles (LNPs) are the most well studied non-viral targeted delivery systems. They are specialized for encapsulating nucleic acids and can be altered with ligands to improve delivery specificity. Compared to other synthetic polymer nanoparticles, LNPs have better biocompatibility and lower levels of toxicity. Currently, the liver is the most efficiently targeted organ for LNP based therapeutics. However, due to low delivery efficiency to primary cells and in in vivo animal experiments, the editing efficiency of LNPs is yet to meet clinical requirements in extra-hepatic tissues. After LNPs, polymer-based nanoparticles (PNPs) are the most used delivery vehicles. PNPs offer several benefits over LNPs since they are easier to manufacture, can be varied easily, and have improved circulation time. Inorganic nanoparticles are also gaining popularity as a vehicle for CRISPR based machinery due to their ability to be modified and their efficacy as a carrier for nucleic acids and small molecules. Other bio-inspired delivery vehicles such as exosomes, liposomal drug delivery systems, antibody/protein carriers, virus-like particles such as bacteriophages and nanobots have shown potential but have remained largely underutilized in the genome editor delivery field. Target Area 2 The blood–brain barrier (BBB) is comprised of endothelial cells in the brain vasculature, as well as specialized glial cells (astrocytes) which surround blood vessels in the brain. The BBB prevents unwanted substances from entering into the extracellular fluid of the central nervous system. Given the vital importance of brain function, it is imperative that the influx and efflux of biological substances be carefully controlled for the appropriate functioning of the central nervous system. One practical consequence of the BBB is that it also blocks the uptake of many pharmaceuticals, including proteins and nucleic acids. This hinders development of treatments for brain related diseases. As such, an effective technology to deliver genome editing machinery across the blood-brain barrier to a substantial proportion of clinically relevant brain cell types would have broad implications for the treatment of many neurogenetic diseases. Timeline 06/01/23 12:00 PM EDT: Informational Webinar 10/05/23 05:00 PM EDT: Phase 1 Submission Deadline 12/13/23 09:00 AM EST: Phase 1 Winners Announced 12/13/23 09:00 AM EST: Phase 2 Launch 01/25/24 12:00 PM EST: Phase 2 Informational Webinar 11/01/24 05:00 PM EDT: Phase 2 Registration Deadline 01/10/25 05:00 PM EST: Phase 2 Submission Deadline 03/06/25 09:00 AM EST: Phase 3 Launch 05/12/25 09:00 AM EDT: Phase 2 Winners Announced (est.) 07/14/25 05:00 PM EDT: Phase 3a Submission Deadline 08/29/25 09:00 AM EDT: Phase 3a Winners Announced 08/29/25 09:00 AM EDT: Phase 3b Reagent Scale-Up 05/04/26 05:00 PM EDT: Phase 3b Deadline (Reagent Delivery Deadline) 09/30/27 09:00 AM EDT: Testing Center Independent Validation 09/30/27 09:00 AM EDT: Phase 3b Winners Announced (est.) Prizes Total cash prizes $6,000,000 Non-monetary prizes Honorable mention recognition; results of independent testing Prize description Amount of the Prize The cash prizes for this Challenge total $6,000,000 USD. Prizes will be awarded following the successful completion of each Phase of the Challenge in the following amounts: Phase 1: Proposals $75,000 per winner, up to 10 winners across Target Areas Prizes of up to $50,000 may be awarded to additional meritorious solutions on the basis of the Judging Criteria Phase 2: Preliminary Data $250,000 per winner, up to 10 winners across Target Areas Phase 3a: Readiness for Large Animal Testing through NIH-Supported Independent Evaluation $50,000 per winner, up to 6 total winners across Target Areas Additional $40,000 per winner in Target Area 2 Phase 3b: Independent Testing and Validation Note: All Phase 3b participants will receive the results of the independent testing of their solution. 1st Place: $625,000 to the first place winner in each Target Area 2nd Place: $225,000 to the second place winner in each Target Area 3rd Place: Honorable Mention to the third place winner in each Target Area Any prize funds unawarded at the completion of earlier phases of this Challenge may be allocated to future phase(s) of the Challenge. Any such allocation of and decisions to award the unspent prize funds in future phases, including modification of prize categories, prize amounts and/or prize number, is entirely at the discretion of NIH. Prior to awarding Phase 3 prizes, winners must sign the PADP agreement. Award Approving Official: The Award Approving Official will be the Director of the Office of Strategic Coordination, within the Division of Program Coordination, Planning, and Strategic Initiatives (DPCPSI) in the NIH Office of the Director. Payment of the Prize: Prizes awarded under this Challenge will be paid by electronic funds transfer and may be subject to federal income taxes. HHS/NIH will comply with the Internal Revenue Service withholding and reporting requirements, where applicable. Entities participating in this Challenge are encouraged, but not required, to request and obtain a free Unique Entity ID (UEI), if they have not already done so, via SAM.gov as this will expedite prize payment. Additional information can be found at https://sam.gov/content/entity-registration. If participating as a Team, in the event of winning a cash prize, the Team Leader shall be paid the prize in full and is solely responsible for allocating any prize amount among the members of the Team. If participating as an Entity, in the event of winning a cash prize, the prize will be paid directly to the Entity, not the Entity Point of Contact. NIH will not arbitrate, intervene, advise on, or resolve any matters between team members. NIH reserves the right, in its sole discretion, to (a) cancel, suspend, or modify the Challenge, or any part of it, for any reason, and/or (b) not award any prizes if no submissions are deemed worthy. Rules Eligibility requirements The following Eligibility and Participation Rules will apply to this Challenge. NIH reserves the right to modify or amend these Rules for any subsequent Phase in order to best achieve the goals of the Challenge and advance the mission of the NIH. NIH may consider amending the Participation Rule regarding intellectual property and licensing of technologies in order to more effectively promote the development of therapeutics for a large number of diseases, including diseases that rarely attract private sector interest. Participants will be notified of any such changes prior to the launch of each Phase. Only Phase 2 winners are eligible to participate in Phase 3. Eligibility Rules: Participants may register for and compete in this Challenge in one of two ways: either as a Team (i.e., registering as a group of individuals competing together but not on behalf of an established organization, institution, or corporation), or as an Entity (i.e., registering as a group of individuals competing together on behalf of a legally established organization, institution, or corporation). To be eligible to win a prize under this Challenge, a Participant (whether a Team or an Entity) — Shall have registered to participate in the Challenge under the rules promulgated by the National Institutes of Health (NIH) as published in this announcement; Shall have complied with all the requirements set forth in this announcement; In the case of an Entity, shall be incorporated in and maintain a primary place of business in the United States. In the case of a Team, the Team Leader shall be a citizen or permanent resident of the United States. However, non-U.S. citizens and non-permanent residents can participate as a member of a Team or Entity that otherwise satisfies the eligibility criteria. Non-U.S. citizens and non-permanent residents are not eligible to win a monetary prize (in whole or in part). Their participation as part of a winning Team or Entity, if applicable, may be recognized when the results are announced. Shall not be a federal entity or federal employee acting within the scope of their employment; Shall not be an employee of the Department of Health and Human Services (HHS, or any other component of HHS) acting in their personal capacity; Who is employed by a federal agency or entity other than HHS (or any component of HHS), should consult with an agency ethics official to determine whether the federal ethics rules will limit or prohibit the acceptance of a prize under this Challenge; Shall not be a judge of the Challenge, or any other party involved with the design, production, execution, or distribution of the Challenge or the immediate family of such a party (i.e., spouse, parent, stepparent, child, or stepchild). Shall be 18 years of age or older at the time of submission IP Considerations: Through the TARGETED Challenge, NIH aims to maximize public access to the winning delivery technology solutions (as defined as the delivery vehicle for the genome editing machinery), and to maximize the number of people who can benefit from therapeutic genome editing utilizing the winning delivery technologies, regardless of the prevalence of their disease. To balance these objectives with encouraging appropriate licensing and commercialization of the technology, the NIH is requiring participants to include a Public Access and Dissemination Plan (PADP) as part of the submission. Instructions for how to prepare this are given in the “How to Enter” section. NIH reserves the right, in its sole discretion, to (a) cancel, suspend, or modify the Challenge, or any part of it, for any reason, and/or (b) not award any prizes if no submissions are deemed worthy. Public Access and Dissemination Plan (PADP): As part of Phase 2 of the Challenge, participants were required to submit a plan (the PADP) to maximize public access to the winning delivery technology solutions, and to maximize the number of people who can benefit from therapeutic genome editing utilizing the winning delivery technologies, regardless of the prevalence of their disease. As described in the Rules section of this Announcement, to receive an award, Participants will be required to agree to abide by the terms of the PADP submitted by the Participants in Phase 2 of the Challenge. Additionally, NIH intends to post or otherwise publicly display the PADP submitted by the Participants on the web or elsewhere. Participation Rules: Federal grantees and recipients of cooperative agreements or other transaction (OT) awards are eligible to participate in the Challenge but may not use Federal funds from a grant award, cooperative agreement, or OT award to develop their Challenge submission or to fund efforts in support of their Challenge submission unless use of such funds is consistent with the purpose, terms, and conditions of the grant award, cooperative agreement, or OT award. Each Participant (whether participating as a Team or Entity) intending to use Federal grant, cooperative agreement, or OT award funds must register for and participate in the Challenge as an entity on behalf of the awardee institution, organization, or entity. If a winning Participant uses Federal grant, cooperative agreement, or OT award funds to participate in the Challenge, the prize must be treated as program income for purposes of the original grant, cooperative agreement, or OT award in accordance with applicable Uniform Administrative Requirements, Cost Principles, and Audit Requirements for Federal Awards [2 CFR § 200]. Participants using Federal grant, cooperative agreement, or OT award funds to participate and/or report prize funding as program income (for winning Participants) should coordinate with the awarding official at the federal awarding agency. Federal contractors may not use federal funds from a contract to develop their Challenge submissions or to fund efforts in support of their Challenge submissions. By participating in this Challenge, each Participant (whether participating as a Team or an Entity) agrees to assume any and all risks and waive claims against the federal government and its related entities, except in the case of willful misconduct, for any injury, death, damage, or loss of property, revenue, or profits, whether direct, indirect, or consequential, arising from participation in this Challenge, whether the injury, death, damage, or loss arises through negligence or otherwise. Based on the subject matter of the Challenge, the type of work that it will possibly require, as well as an analysis of the likelihood of any claims for death, bodily injury, property damage, or loss potentially resulting from Challenge participation, no Participant (whether participating as a Team or an Entity) participating in the Challenge is required to obtain liability insurance, or demonstrate financial responsibility, or agree to indemnify the federal government against third party claims for damages arising from or related to Challenge activities in order to participate in this Challenge. A Participant (whether participating as a Team or an Entity) shall not be deemed ineligible because the Participant used federal facilities or consulted with federal employees during the Challenge if the facilities and employees are made available to all Participants participating in the Challenge on an equitable basis. By participating in this Challenge, each Participant (whether participating as a Team or an Entity) warrants that they are sole author or owner of, or has the right to use, any copyrightable works that the submission comprises, that the works are wholly original with the Participant (or is an improved version of an existing work that the Participant has sufficient rights to use and improve), and that the submission does not infringe any copyright or any other rights of any third party of which the Participant is aware. By participating in this Challenge, each Participant (whether participating as a Team or an Entity) grants to the NIH an irrevocable, paid-up, royalty-free nonexclusive worldwide license to reproduce, publish, post, link to, share, and display publicly the submission title and executive summary on the web or elsewhere. Each Participant will retain all other intellectual property rights in their submissions, as applicable. To participate in the Challenge, each Participant must warrant that there are no legal obstacles to providing the above-referenced nonexclusive licenses of the Participant’s rights to the federal government. To receive an award, Participants will not be required to transfer their intellectual property rights to NIH, but Participants must grant to the federal government the nonexclusive licenses recited herein. Each Participant (whether participating as a Team or an Entity) agrees to follow all applicable federal, state, and local laws, regulations, and policies, including the Animal Welfare Act as applicable, and any other applicable laws, regulations, and policies regarding animal welfare. Each Participant (whether participating as a Team or an Entity) participating in this Challenge must comply with all terms and conditions of these rules, and participation in this Challenge constitutes each such Participant’s full and unconditional agreement to abide by these rules. Winning is contingent upon fulfilling all requirements herein. As a condition for winning a cash prize in this Challenge, each Participant (whether participating as a Team or an Entity) that has been selected as a winner must complete and submit all requested winner verification and payment documents to NIH within 7 business days of formal notification. Failure to return all required verification documents by the date specified in the notification may be a basis for disqualification of a cash prize winning submission. By participating in this Challenge, each Participant (whether participating as a Team or an Entity) irrevocably grants to NIH the right to the use of their name, affiliation, city and state, and likeness or image for the purposes of publicity releases and any other promotion of this Challenge. By participating in this Challenge, each Participant (whether a group of individuals or entity) grants to the NIH an irrevocable, paid-up, royalty-free nonexclusive worldwide license to reproduce, publish, post, link to, share, and display publicly the submission (including the Public Access and Dissemination Plan (PADP) submitted by the Participants) on the web or elsewhere, and agrees to grant a nonexclusive, nontransferable, irrevocable, paid-up license to practice, or have practiced for or on its behalf, the solution throughout the world. Each Participant will retain all other intellectual property rights in their submissions, as applicable. To participate in the Challenge, each Participant must warrant that there are no legal obstacles to providing the above-referenced nonexclusive licenses of the Participant’s rights to the federal government. To receive an award, Participants will not be required to transfer their intellectual property rights to NIH, but Participants must grant to the federal government the nonexclusive licenses recited herein and any license in the Participant’s PADP. To receive an award, Participants will be required to agree to abide by the terms of the PADP submitted by the Participants for this Challenge. Judging Phase 1: Proposals (closed) Target Area 1: Programmable Delivery System for Gene Editing Ability to Solve the Challenge – 60 points Clear explanation and scientific rationale/evidence base/validity of programmable mechanism (25 points) Anticipated and/or demonstrated diversity of anticipated tissue targets (cells, type, and/or organs) (15 points) Anticipated and/or demonstrated quantity of tissue targets (cells, type, and/or organs) (10 points) Anticipated and/or demonstrated efficiency of delivery system for genome editing machinery (compared to current state of the art) (10 points) Innovation – 20 points Explanation of how the solution is innovative and how it will impact the current state of technology Capability to Execute – 15 points Feasibility of completing a compelling Phase 2 submission based on facilities, environment, personnel, and milestone plan Quality of Submission – 5 points Submission is complete, addresses the Challenge, and is presented clearly Total 100 points Extra Credit Preliminary Data – 10 points Quality of Participant-generated preliminary data and demonstrated potential success Potential Impact – 10 points Market potential for technology, manufacturability (scalability and cost-effectiveness), competitive landscape, and/or potential to address unmet medical needs Target Area 2: Crossing the Blood-Brain Barrier Ability to Solve the Challenge - 60 points Demonstrated ability and/or potential to traverse the BBB, based on supporting evidence and/or scientific rationale for potential (25 points) Demonstrated ability and/or potential to target and edit a substantial proportion of clinically relevant cell types in the brain (25 points) Anticipated and/or demonstrated editing efficiency of delivery system when delivering genome editing machinery (compared to current state of the art) (10 points) Innovation – 20 points Explanation of how the solution is innovative and how it will impact the current state of technology Capability to Execute – 15 points Feasibility of completing a compelling Phase 2 submission based on facilities, environment, personnel, and milestone plan Quality of Submission 5 points Submission is complete, addresses the Challenge, and is presented clearly Total 100 points Extra Credit Preliminary Data – 10 points Quality of Participant-generated preliminary data and demonstrated potential success Manufacturing Considerations – 10 points Scalability and cost-effectiveness of manufacturing Judging Panel All submissions that are responsive and meet the Eligibility Rules and Submission Requirements will be evaluated and scored by qualified expert employee(s) of the federal government using the criteria and scoring rubric described above. The results of the evaluation will be provided to a Judging Panel composed of NIH senior leaders. The Judging Panel will select Winners based on the individual and overall evaluation scores and the diversity of technologies and/or targets of the highest scoring solutions. The selected Winners will be submitted to the Award Approving Official for a final decision. NIH will not make Participants’ evaluation or judging results available to Participants or the public. Phase 2: Preliminary Data (closed) Phase 2 Judging Criteria Target Area 1: Programmable Delivery System for Gene Editing Ability to Solve the Challenge – 60 points Demonstrated efficiency of the delivery system for delivering genome editing machinery to the intended targets (compared to current state of the art delivery systems) (25 points) Mechanistic demonstration that the delivery system is modifiable so that it is programmable with ability to specifically target different cell types, tissues, and/or organ(s) (15 points) Demonstration of the diversity and quantity of tissue targets (cells, types, and/or organs), i.e., data which supports the ability to target 3+ configurations (10 points) Rationale for the technology to reach additional targets beyond for which data is provided (5 points) Demonstration of the editing capacity for genome editing machinery within the delivery system (5 points) Translatability – 15 points Data or information that demonstrates the technology can move between species. Data that demonstrate that the solution can move from model systems into the clinic. Capability to Execute – 10 points Feasibility of completing a compelling Phase 3 submission based on facilities, environment, personnel, and milestone plan. Potential Impact – 10 points Market potential for technology, manufacturability (scalability and cost-effectiveness), competitive landscape, and/or potential to address unmet medical needs. Public Access and Dissemination Plan (PADP) – 5 points Potential for and feasibility of maximizing the number of people who can benefit from therapeutic genome editing utilizing the winning delivery technologies, regardless of the prevalence of their disease, through broad dissemination, non-exclusive research licensing, and other potential licensing scenarios. Total 100 points Target Area 2: Crossing the Blood-Brain Barrier Ability to Solve the Challenge – 60 points Demonstrated efficiency of delivery system for delivering genome editing machinery to the intended targets (compared to current state of the art delivery systems) (25 points) Demonstration that the delivery system crosses the blood-brain barrier (15 points) Demonstration of the solution’s ability to target a substantial number of clinically relevant cell types of the brain (15 points) Demonstration of the editing capacity for genome editing machinery within the delivery system (5 points) Translatability – 15 points Data or information that demonstrates the technology can move between species. Data that demonstrate that the solution can move from model systems into the clinic. Capability to Execute – 10 points Feasibility of completing a compelling Phase 3 submission based on facilities, environment, personnel, and milestone plan. Potential Impact – 10 points Market potential for technology, manufacturability (scalability and cost-effectiveness), competitive landscape, and/or potential to address unmet medical needs. Public Access and Dissemination Plan (PADP) – 5 points Potential for and feasibility of maximizing the number of people who can benefit from therapeutic genome editing utilizing the winning delivery technologies, regardless of the prevalence of their disease, through broad dissemination, non-exclusive research licensing, and other potential licensing scenarios. Total 100 points Evaluation and Judging All submissions that are responsive and meet the Eligibility Rules and Submission Requirements will be evaluated and scored by qualified expert employee(s) of the federal government using the criteria and scoring rubric described above. The results of the evaluation will be provided to a Judging Panel composed of NIH senior leaders. The Judging Panel will select Winners based on the individual and overall evaluation scores and the diversity of technologies and/or targets of the highest scoring solutions. Because NIH aims to maximize public access to the winning delivery technology solutions, and to maximize the number of people who can benefit from therapeutic genome editing utilizing the winning delivery technologies, regardless of the prevalence of their disease, the judging panel will give great consideration to the evaluation of the PADP in their selection of Winners. The selected Winners will be submitted to the Award Approving Official for a final decision. NIH will not make Participants’ evaluation or judging results available to Participants or the public. Phase 3: Final Data, Independent Testing, and Validation (open until 05/04/26) Phase 3a Judging Criteria: Submissions for Phase 3a will be reviewed by NIH, from which up to 6 submissions will be selected to continue to Phase 3b. The review will consider: Completeness of the information requested in fulfillment of the Phase 3a submission requirements Readiness for testing, including: Ability to scale up and deliver reagents Complete and rigorous protocol for testing Complete plan for shipping reagent(s) Final data demonstrating effectiveness of solution and readiness for large animal testing Potential clinical impact of solution How solution addresses unmet medical needs Biomanufacturing and scale-up Potential for scaling up to larger volumes Potential for production of high-quality, clinical grade materials Phase 3b Judging/Evaluation Criteria: Phase 3b review criteria will focus on results from the NIH independent evaluation in large animal models. This will include sufficient feasibility data and evidence of successful delivery of gene editing machinery, as noted in the Phase 3b Judging Criteria. Target Area 1 requires demonstration of delivery and editing in at least three different cell types, tissues, and/or organs. Target Area 2 requires demonstration of crossing the blood-brain barrier (BBB) and editing in relevant cells in the CNS. Evaluation Criteria for Target Area 1: Programmable Delivery System for Gene Editing Ability to Solve the Challenge as Demonstrated from the Independent Testing Center Data - 75 points Demonstrated efficiency of the delivery system for delivering genome editing machinery to the intended targets (compared to current state of the art delivery systems). (20 points) Mechanistic demonstration that the delivery system is modifiable so that it is programmable with ability to specifically target different cell types, tissues, and/or organ(s). (20 points) Demonstration of the variety and quantity of tissue targets (cell types, tissues, and/or organs), i.e., data which supports the ability to target 3+ configurations. (15 points) Rationale for the technology to reach additional targets beyond those for which data are provided.(10 points) Demonstration of the editing capacity of the genome editing machinery within the delivery system. (10 points) Translatability - 15 points Data or information demonstrating the technology can be effective in different species, and data demonstrating that the solution can move from model systems into the clinic. Potential Impact - 10 points Market potential for the technology, manufacturability (scalability and cost-effectiveness), competitive landscape, and/or potential to address unmet medical needs as described in Phase 3a submission. Total 100 points Evaluation Criteria for Target Area 2: Crossing the Blood-Brain Barrier (BBB) Ability to Solve the Challenge as Demonstrated from the Independent Testing Center Data - 80 points Demonstration that the delivery system crosses the BBB. (30 points) Demonstration of the solution’s ability to target a substantial number of clinically relevant cell types of the brain. (30 points) Demonstration of the editing capacity of the genome editing machinery within the delivery system. (20 points) Translatability Data demonstrating that the solution can move from models into the clinic. (10 points) Potential Impact Market potential for the technology, manufacturability (scalability and cost-effectiveness), and competitive landscape, and/or potential to address unmet medical needs as described in Phase 3a submission. (10 points) Total 100 points In addition, the judges may also review and evaluate any information submitted by the solver in earlier Phases of the Challenge, including Phase 3a. Such information may include: data from models in Phase 2; feasibility of rapid scale-up for manufacturing as demonstrated; how well the solution may address ultrarare diseases; and commercialization potential, i.e. economic viability and potential to be on the market within the next ~5 years. Judging Panel: All submissions that are responsive and meet the Eligibility Rules and Submission Requirements will be reviewed and scored by qualified expert employee(s) of the federal government using the criteria and scoring rubric described above. The results of the review will be provided to a Judging Panel composed of NIH senior leaders. The Judging Panel will select Winners based on the individual and overall review scores, the variety of technologies and/or targets of the highest scoring solutions, and the PADP. The selected Winners will be submitted to the Award Approving Official for a final decision. NIH will not make Participants’ evaluation or judging results available to Participants or the public. How to enter Phase 1: Proposals (closed) Registration and Submission Process: Participants may register for and compete in this Challenge in one of two ways: either as a Team (i.e., registering as a group of individuals competing together but not on behalf of an established organization, institution, or corporation), or as an Entity (i.e., registering as a group of individuals competing together on behalf of a legally established organization, institution, or corporation). For Teams: Each participating Team is required to identify a Team Lead who will register and submit on behalf of the Team members. The Team Lead is responsible for all communications with the Challenge sponsors and, in the event of winning a cash prize, will be paid the prize in full. To be eligible to receive a cash prize, the Team Lead must be a citizen or permanent resident of the United States. In the event that a dispute regarding the identity of the Team Lead who actually submitted the entry cannot be resolved to NIH’s satisfaction, the affected submission will be deemed ineligible. For Entities: Each participating Entity is required to identify a Point of Contact who will register and submit on behalf of the Entity. The Point of Contact is responsible for all communications with the Challenge sponsors. In the event of winning a cash prize, the prize will be paid directly to the Entity, not to the Point of Contact. To be eligible to receive a cash prize, the Entity must be incorporated in and maintain a primary place of business in the United States. As stated in the Participation Rules, Participants intending to use Federal grant, cooperative agreement, or OT funds (where permissible) must register for and participate in the Challenge as an Entity on behalf of the awardee institution or organization. In the event that a dispute regarding the identity of the Point of Contact who actually submitted the entry cannot be resolved to NIH’s satisfaction, the affected submission will be deemed ineligible. Submission Requirements: Phase 1 – Proposal Submissions for Phase 1 of the Challenge must describe your proposed targeted delivery system for genome editing, how the technology will address the solution requirements, and your ability to conduct studies that demonstrate delivery and editing performance prior to the deadline for Phase 2. To compete in Phase 1, Participants will need to upload PDFs of all required materials prior to the deadline of October 5, 2023, at 5pm ET. Note: Participants may submit more than one solution to Phase 1 of the Challenge. However, each submission must be a substantially different solution. For example, if the solutions use different technology or use a novel approach to the solution or are solutions for different Target Areas, those may be separate submissions. If the solutions are variations using the same technology and only have minor differences, they should be submitted as a part of a single submission, and you must explain the differences between your solutions or the variations within your solution. All submissions must be written in English and cannot be handwritten. NIH requires 1” margins, the use of font that is at least 11 pt in size, and generally recommends the use of either Arial, Georgia, Helvetica, or Palatino Linotype. For your submission to be considered, each Participant must (whether a Team Lead or Entity POC): Be eligible to compete as defined by the Eligibility Rules. Register on the Challenge website by completing and submitting the Registration Form. Upload a Proposal in PDF format. Each Proposal submission must include: Cover page (1 page) Team or Entity Name Logo (optional) Team or Entity location (State, Country) Team Lead’s or Entity POC’s Freelancer account username Executive Summary including submission title, description of the Team’s or Entity’s proposed solution and how it will best achieve all the goals of the Challenge. (1 page) Project Description (up to 5 pages not including images or references) For the Target Area 1: Programmable Delivery System for Gene Editing you must describe: The anticipated targets: Include the quantity and diversity of the anticipated targets, and which targets associated with the technology have some proof of concept. Demonstrated understanding of the programmable mechanism: Include how the delivery system is modifiable so that it is programmable to target different cell types, tissues, and/or organ(s). Describe what is done to modify the technology to deliver to different cells/tissue/organ targets and how this relates to the underlying biology and/or biochemistry of the system. The demonstrated or anticipated efficiency of the system to deliver genome editing machinery compared to existing technologies: provide data and/or an explanation with the basis of the anticipated efficiency. Why and how the solution is innovative in addressing the Challenge requirements. The technology’s market potential, competitive landscape, manufacturability (scalability and cost-effectiveness), and/or potential to address unmet medical needs. For Target Area 2: Crossing the Blood-Brain Barrier, you must describe: The solution’s potential for or data showing evidence for traversing the BBB. The solution’s potential for or data showing the ability to target a substantial number of clinically relevant cell types. The solution’s potential for delivery of genome editing machinery and/or preliminary data demonstrating editing efficiency. Why and how the solution is innovative in addressing the Challenge requirements. Description of manufacturing considerations for this technology, including scalability and cost-effectiveness. Data (up to 2 additional pages may be provided after the project description to include tables or figures) Provide any data to support your targeted delivery system including but not limited to internal data from Participants, collaborators and/or proof-of-concept data supported by the scientific literature. Clearly distinguish which data, if any, was generated by members of the Participant Team or Entity. Provide relevant citations related to this work or to other work related to your solution. Phase 2 Capability (up to 3 pages) Description of planned activities and milestones on a timeline that will enable successful Phase 2 submission. List the key Team or Entity members and why the Team or Entity is well-suited to solve the Challenge. Include key information on their qualifications, experience, skills, and/or capabilities that are relevant to achieving the goals of the Challenge. Describe facilities and environment that will be used to complete work in Phase 2. If applicable, describe plans to ensure planned activities will comply with applicable animal welfare laws, regulations, and policies, including any overarching frameworks in place to address concerns with regard to animal safety and protections, and the committee(s) that would approve those studies. Supporting Documents If the submission contains any Participant-generated animal data, for each study provide a description of the overarching frameworks that were in place to address concerns with regard to animal safety and protections, identify the committee that approved the study, and certify that the data was collected in compliance with applicable animal welfare laws, regulations, and policies. Letters of support for your project from proposed facilities, anticipated future collaborators, and/or your organization or company. Phase 2: Preliminary Data (closed) Registration Process: Participants may register for and compete in this Challenge in one of two ways: either as a Team (i.e., registering as a group of individuals competing together but not on behalf of an established organization, institution, or corporation), or as an Entity (i.e., registering as a group of individuals competing together on behalf of a legally established organization, institution, or corporation). For Teams: Each participating Team is required to identify a Team Lead who will register and submit on behalf of the Team members. The Team Lead is responsible for all communications with the Challenge sponsors and, in the event of winning a cash prize, will be paid the prize in full. To be eligible to receive a cash prize, the Team Lead must be a citizen or permanent resident of the United States. In the event that a dispute regarding the identity of the Team Lead who actually submitted the entry cannot be resolved to NIH’s satisfaction, the affected submission will be deemed ineligible. For Entities: Each participating Entity is required to identify a Point of Contact who will register and submit on behalf of the Entity. The Point of Contact is responsible for all communications with the Challenge sponsors. In the event of winning a cash prize, the prize will be paid directly to the Entity, not to the Point of Contact. To be eligible to receive a cash prize, the Entity must be incorporated in and maintain a primary place of business in the United States. As stated in the Participation Rules, Participants intending to use Federal grant, cooperative agreement, or OT funds (where permissible) must register for and participate in the Challenge as an Entity on behalf of the awardee institution or organization. In the event that a dispute regarding the identity of the Point of Contact who actually submitted the entry cannot be resolved to NIH’s satisfaction, the affected submission will be deemed ineligible. Phase 2 Submission Requirements: Registered Participants will receive communications from the NIH-contracted Challenge Team, including summaries of clarification questions, notifications of informational webinars, any changes to the Challenge dates, and additional guidance on the challenge. To Register for the Challenge: Create an account on Freelancer.com Complete the Registration Form All Participants must complete a new Phase 2 Registration Form Phase 2 Registration Form All Phase 2 Participants must complete a Phase 2 Registration Form by the Registration deadline of November 1, 2024 5pmET. Late registrations are not guaranteed to be accepted but will be considered on a case by case basis. The Phase 2 Registration Form asks for background information about the Participants and a 1-page Executive Summary describing your solution. Participants who also participated in Phase 1 must submit a Phase 2 Registration form; your Executive Summary can either be the one you submitted for Phase 1 or be updated to reflect the current state of your work (the latter is preferred). Submission Requirements Phase 2 Submissions will be required to address how the solution meets the solution requirements for the Target Area, provide detailed information about submitted experimental results, and give a description of the methodologies used (including frameworks used to ensure appropriate animal protections for any animal experiments included in the submission). Submissions must include data/results from studies that demonstrate and quantify delivery and editing performance. Solutions submitted to both Target Areas with a single approach to delivery are only eligible for one prize. A team and/or entity may be eligible for multiple prizes for multiple solutions if the solutions are qualitatively different. Participants will need to upload PDFs of all required materials prior to the deadline of January 10, 2025, at 5pm ET. All submissions must be written in English and cannot be handwritten. NIH requires 1” margins, the use of font that is at least 11 pt in size, and generally recommends the use of either Arial, Georgia, Helvetica, or Palatino Linotype. It is recommended that the written document has at least 1.0 line spacing. For your submission to be considered, each Participant (whether a Team Lead or Entity POC) must: Be eligible to compete as defined by the Eligibility Rules. Register on the Challenge website by completing and submitting the Registration Form. Upload a Submission in PDF format according to the above-mentioned requirements. Submissions for Phase 2 of the Challenge must be full and complete. The Evaluation and Judging Panels will only consider what has been submitted as part of the Phase 2 (Registration and Submissions). The Judging Panel will have no knowledge of anything submitted for Phase 1 (if applicable). Participants may only submit to one Target Area. Note: Ensure your submission meets all the requirements for the appropriate Target Area. Provide data to support your targeted delivery system including but not limited to internal data from Participants or collaborators and/or proof-of-concept data supported by the scientific literature. Clearly distinguish which data, if any, was generated by members of the Participant Team or Entity. Provide relevant citations related to this work or to other work related to your solution. Each Submission Must Include: Cover Page Team or Entity Name Logo (optional) Team or Entity location (State, Country) Team Lead’s or Entity POC’s Freelancer account username Executive Summary (1 page, no graphics/figures) Project and Data (up to 10 pages inclusive of project description and all figures, tables and data. Preferable to be organized and be presented in the order stated below to facilitate evaluation and judging stages) For Target Area 1: Programmable Delivery System for Gene Editing: Describe the targets including the quantity and diversity of the targets (at least three different cell types, tissues and/or organs): Provide proof of concept for the targets associated with the technology. Demonstrate the programmable mechanism: provide data showing delivery to different targets and describe how the delivery system is modifiable to be programmable, as defined in the Challenge summary, to target different cell types, tissues, and/or organ(s) and how this relates to the underlying biology and/or biochemistry of the system. Demonstrate the efficiency of the system used to deliver genome editing machinery compared to existing technologies: provide data and/or an explanation with the basis of the comparative editing efficiency to existent technologies. If data are not available for more than the minimum of three (3) configurations at the time of the Phase 2 submission, provide rationale that the solution can reach additional configurations, i.e., potential to reach additional targets beyond those for which data is provided should be described. Describe why and how the solution is innovative in addressing the Challenge requirements. For Target Area 2: Crossing the Blood-Brain Barrier: Demonstrate the capability to traverse the BBB: provide data demonstrating evidence for the capability of the solution to traverse the BBB. Demonstrate the ability to target a substantial number of clinically relevant cell types of the brain: provide data showing the solution targeting different cell types. Demonstrate the delivery efficiency of the system used to deliver genome editing machinery compared to existing technologies: provide data and/or an explanation with the basis of the delivery efficiency to current state-of-the art comparative technologies. Describe why and how the solution is innovative in addressing the Challenge requirements. For both Target Area 1 and Target Area 2, you must include: Translatability: Describe why and how the solution is translatable: how the solution can be used across species and/or models but ultimately the solution can be used for clinical therapeutics in humans. Describe the translatability of the technology linking cellular processes in models to cross-species translation ultimately with ability for application of clinical use. Potential Impact: Describe the technology’s market potential: potential clinical impact if the technology enters the market, describe the business use case, competitive landscape, manufacturability (scalability and cost-effectiveness), and/or potential to address unmet medical needs. Description of manufacturing considerations for this technology, including scalability, accessibility, and cost-effectiveness. Demonstrated Capability to Move into Phase 3 (up to 3 pages) Describe the feasibility of scaling up reagents at sufficient quality and purity for large animal validation to be performed by the NIH. Describe planned activities and milestones on a timeline that will enable successful Phase 3 submission. List key Team or Entity members and why the Team or Entity is well-suited to solve the meet the work needed for Phase 3. Include key information on their qualifications, experience, skills, and/or capabilities that are relevant to achieving the goals for Phase 3. Describe facilities and environment that will be used to complete work in Phase 3. Public Access and Dissemination Plan (PADP) (up to 5 pages) Participants must submit a plan (the PADP) to maximize public access to the winning delivery technology solutions, and to maximize the number of people who can benefit from therapeutic genome editing utilizing the winning delivery technologies, regardless of the prevalence of their disease. The PADP must describe how winners will disseminate information about the solution and make the solution, as well as the knowledge necessary to generate the delivery vehicle and incorporate the genome editor, available under non-exclusive licenses for research purposes. Such purposes must explicitly include Phase I/2 clinical trials in humans, as well as studies leading up to such trials (e.g., proof of concept studies, biodistribution, toxicology studies). The PADP must describe how the winner would allow others to utilize the solution in the event the winner is unable themselves to maximize public access to the solution and the number of people that can benefit from therapeutic genome editing. The PADP must include specific licensing schemes and scenarios when such schemes would be employed. The PADP must describe how the winner will permit the U.S. government to allow interested parties to utilize the solution if the winner themselves fails to utilize the solution and does not permit others to utilize the solution under reasonable terms. The plan must describe any licensing schemes and scenarios that will accomplish this plan. As described in the Rules section of this Announcement, to receive an award, Participants will be required to agree to abide by the terms of the PADP submitted by the Participants for this Challenge. Additionally, NIH intends to post or otherwise publicly display the PADP submitted by the Participants on the web or elsewhere. Supporting Documents (no page limit, suggested to be presented in this order if documents are available to facilitate evaluation and judging) References for citations included in the submission. Additional documentation in support of the PADP (e.g., examples of licensing agreements or specific schemes or scenarios) If the submission contains any Participant-generated animal data, for each study provide a description of the overarching frameworks that were in place to address concerns regarding animal safety and protections, identify the committee that approved the study, and certify that the data were collected in compliance with applicable animal welfare laws, regulations, and policies. Optional letters of support for your project (e.g., from facilities, cores, collaborators). Phase 3: Final Data, Independent Testing, and Validation (open until 05/04/26) Registration Process: Participants may register for and compete in this Challenge in one of two ways: either as a Team (i.e., registering as a group of individuals competing together but not on behalf of an established organization, institution, or corporation), or as an Entity (i.e., registering as a group of individuals competing together on behalf of a legally established organization, institution, or corporation). For Teams: Each participating Team is required to identify a Team Lead who will register and submit on behalf of the Team members. The Team Lead is responsible for all communications with the Challenge sponsors and, in the event of winning a cash prize, will be paid the prize in full. To be eligible to receive a cash prize, the Team Lead must be a citizen or permanent resident of the United States. In the event that a dispute regarding the identity of the Team Lead who actually submitted the entry cannot be resolved to NIH’s satisfaction, the affected submission will be deemed ineligible. For Entities: Each participating Entity is required to identify a Point of Contact who will register and submit on behalf of the Entity. The Point of Contact is responsible for all communications with the Challenge sponsors. In the event of winning a cash prize, the prize will be paid directly to the Entity, not to the Point of Contact. To be eligible to receive a cash prize, the Entity must be incorporated in and maintain a primary place of business in the United States. As stated in the Participation Rules, Participants intending to use Federal grant, cooperative agreement, or OT funds (where permissible) must register for and participate in the Challenge as an Entity on behalf of the awardee institution or organization. In the event that a dispute regarding the identity of the Point of Contact who actually submitted the entry cannot be resolved to NIH’s satisfaction, the affected submission will be deemed ineligible. Registered Participants will receive communications from the NIH-contracted Challenge Team, including summaries of clarification questions received and responses to those questions, notifications of informational webinars, any changes to the Challenge dates, and any additional guidance on the challenge, as needed. Phase 3a: Participants will be required to: address how the solution meets the requirements for the applicable Target Area; provide the results and methodologies of studies demonstrating that their technology is ready for large animal testing (e.g., preliminary data to justify dose, data to support route of administration/delivery method, or any species-specific optimization studies); and submit a description of planned activities that will enable transfer of reagents to and studies by the NIH-supported independent testing center. At the start of Phase 3a, participants will be provided information about the testing centers, the list of editors that participants must package or attach, route of administration, and all other information needed to complete Phase 3a. Note: NIH will provide standard/uniform editor reagents to groups, such as SaCas9 or SpCas9, and select the target gene. NIH may try to standardize the gene target to make the comparisons across solutions as uniform as possible. Submissions for the BBB target area will be evaluated by two testing centers and will need to be able to double their scale-up. Both target areas will be evaluated in reporter animals for editing and biodistribution. The testing centers will provide information about: Acceptable routes of administration Reagent properties – e.g., reagent viscosity, diluent, concentration, and pH Highest acceptable level of endotoxin Phase 3a Submission Requirements: Participants must upload PDFs of all required materials prior to the deadline of July 14, 2025, at 5pm ET. All submissions must be written in English and cannot be handwritten. NIH requires 1-inch margins and the use of at least 11 pt font size. NIH generally recommends the use of either Arial, Georgia, Helvetica, or Palatino Linotype fonts. It is recommended that the written document has at least 1.0 line spacing, not to exceed 25 pages. For your submission to be considered, each Participant (whether a Team Lead or Entity POC) must: Be eligible to compete as defined by the Eligibility Rules. Be a winner of Phase 2 of the Challenge. Upload a Submission in PDF format according to the above-mentioned requirements. Submissions for Phase 3a of the Challenge must be full and complete. Applications with missing information or details may be excluded from further participation in the Challenge. NIH and the testing centers will be provided with your Phase 2 submission and may use them to compare with your recommendation for Phase 3 testing. Participants may only submit to the Target Area in which they were awarded in during Phase 2. Target Area 2 (BBB) Phase 2 winners will have their solutions tested at both labs under two protocols. Note: Ensure that your submission meets all the requirements for the appropriate Target Area. Provide preliminary data to justify dose, data to support route of administration/delivery method, and/or any species-specific optimization studies. Note: data from Phase 2 can be used. Rationale for the dose proposed must be provided. Provide titer for viral and viral-like solutions; concentrations must be provided for all other reagents. Include specificity of negative readouts that may have happened during the submitter’s testing, as well as findings on adverse events. Describe the impact of your solution. Describe the technology’s market potential, including: potential clinical impact if the technology enters the market; and description of the business use case, competitive landscape, and/or potential to address unmet medical needs. GMP compatible manufacturability: scalability and cost-effectiveness. Include a description of manufacturing considerations for this technology, including scalability, accessibility, and cost-effectiveness. Provide in vivo protocols previously performed by the solver to evaluate ability to move into a larger animal model. These must include all needed information and instructions for the testing center to complete the protocol. Provide all relevant experimental details, including: Species/sex/age of animal(s) tested and N of study groups Cell/tissue/organ target(s) Delivery system and editor information Study duration, including how long before assays for readouts were performed Route of administration (must be IM injection or IV injection, which are the only two routes of administration approved by the testing centers for the purpose of this Challenge) Dose per kg of animal body weight Proposed readouts and metrics of success for delivery and biodistribution for anticipated cell/tissue/organ targets as well as for editing efficiency Note: NIH prefers positive readouts and definitive assays for assessing biodistribution and editing (e.g., screening assays, ELISAs, flow cytometry, qPCR, IHC/IF, RNAScope, etc.) with timepoints. If there are any anticipated adverse effects that a participant wants NIH to look for, include this in the protocol. Any special preparation procedures for preparing the delivery reagent for administration (e.g., procedures to address aggregation or settling of particles) How reagent should be handled (e.g., -80°C or -30°C, specification of initial storage duration(s) at defined temperatures, long-term storage conditions) Any additional information required by the testing center to complete your protocol Provide your plan for scale-up of your reagent(s). The plan must include: General information about methods used for reagent scale-up Details of all components in the reagent(s) Certificates of Analysis (COAs) should contain all essential details of the components and how they were produced. For example, COAs must include quality control and analytical data characterizing the vector particles produced (if viral vector) and purification methods as well as final titer (vg/ml). Laboratory and in vitro grades are not acceptable. Methods and records for assessing quality and purity of testing reagents All vectors/aliquots must be prepared under sterile conditions and must be accompanied with essential details related to preparation and testing, as well as relevant assessments for contaminants. Any potential toxicity Levels of endotoxins 0.5 endotoxin units/milliliter (EU/mL) is the maximum allowable endotoxin level. Additional aliquots must be included for in-house testing and quality control: The testing center must verify sterility and endotoxin level (≤0.5 EU/ml) before administration by any route will be considered. Provide data used for the Certificate of Analysis (COA) reports. In-house results from solvers for evaluating toxicity of reagent(s) How long it will take to scale up the reagent for the lab testing? For Target Area 2 (BBB), how long will it take to scale up the reagent for testing at both labs? Translatability Describe why and how the solution is translatable, including: how the solution can be used across animal species and/or models, and how the solution is designed, ultimately, for clinical/therapeutic application in humans. Describe the translatability of the technology by linking cellular processes in models to cross-species translation and to cellular process in humans in the eventual clinical context. Append any raw data on translatability that supported the Phase 2 submission but were not provided in that submission; add any needed context or additional information that describes how the provided data support translatability. Describe how the intended tissue targeting will work in different animals and in humans. Choice of editors: NIH will provide a list of editors from which the participants may choose. Shipping plan What is your plan to ensure chain of custody and maintenance of reagent integrity during shipping? The plan must include details about packaging, shipping, insurance, tracking, and acknowledgement of reagent receipt by the testing center(s). How will you ensure proper maintenance of the reagent(s) throughout the shipping process (e.g., -80°C, -30°C, or another temperature), and are there any special instructions for transition of shipped reagent(s) to required onsite storage conditions at the testing center(s)? Reagent storage at testing center Since reagent(s) may need to be stored at the testing center(s) up to several months before in vivo testing, provide all needed instructions for long-term, onsite storage at the testing center(s). Points of contact Provide to the NIH and Challenge Team the name(s) and contact information of the person(s) who will oversee Phase 3 on behalf of the Participant (i.e., Team or Entity). Provide to the NIH and Challenge Team the name(s) and contact information of the person(s) who can address questions or issues regarding the reagent(s) and protocols for the testing centers. Phase 3b: Participants will be required to submit the reagents, protocol, assays, and all other necessary information and instructions to the NIH-supported large animal testing centers to independently validate the performance of their solution. The independent validation centers will provide the results of those studies to the NIH and the Participant. Participants may be asked to prepare a final summary of how their solution meets solution requirements after independent validation is complete. Phase 3b Submission Requirements: Participants must coordinate with the NIH Challenge Team and the testing centers to ensure safe delivery of their reagents, protocols, assays, and all other necessary information and instructions. In all Phases, Participants are expected to follow all applicable federal, state, and local laws, regulations, and policies, including the Animal Welfare Act, as applicable, and any other applicable laws, regulations, and policies regarding animal welfare. In each Phase’s submission that includes Participant-generated data from animal studies, Participants will be expected to certify that the data were collected with appropriate animal protections, provide a description of the framework used to ensure appropriate animal protections, specify the committee that approved the studies, and provide a description of how future plans will comply with all applicable animal welfare laws, regulations, and policies. Resources 1-Announcement of Requirements and Registration for the TARGETED Challenge.pdf 2-Announcement of Requirements and Registration for the TARGETED Challenge (Updated 2-20-2025).pdf 3-Announcement of Requirements and Registration for the TARGETED Challenge Phase 3 (Updated 3-6-2025).pdf Contact For Further Information Contact: scgeprogram@od.nih.gov Winners Winners will be announced following judging of submissions. This page last reviewed on December 23, 2025 www.nih.gov An official website of the Department of Health and Human Services Looking for U.S. government information and services? Visit USA.gov