Targeted Genome Editor Delivery (TARGETED) Challenge

Targeted Genome Editor Delivery (TARGETED) Challenge is a grant from the National Institutes of Health (NIH) that funds innovative in vivo delivery technologies for genome editors. The 6,000,000 dollar three-phase competition targets two areas: programmable delivery systems for gene editing, and non-viral delivery across the blood-brain barrier.

Phase 1 awards up to 75,000 dollars per winning proposal; Phase 2 awards up to 250,000 dollars per winner; Phase 3 awards up to 625,000 dollars for top solutions per target area, with individual awards reaching up to 1,000,000 dollars. Winning solutions receive NIH-funded large animal testing for independent validation. Open to individuals and organizations with innovative delivery solutions.

Phase 3 closes May 4, 2026.

Targeted Genome Editor Delivery (TARGETED) Challenge | National Institutes of Health (NIH) Targeted Genome Editor Delivery (TARGETED) Challenge Targeted Genome Editor Delivery (TARGETED) Challenge Revolutionizing technology development of delivery systems for in vivo genome editing. 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 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.

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.

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 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.

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.

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.)

Honorable mention recognition; results of independent testing 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: $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.

1 st Place: $625,000 to the first place winner in each Target Area 2 nd Place: $225,000 to the second place winner in each Target Area 3 rd 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. 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.

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.

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 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.

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) 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.

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) 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 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) 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 Preliminary Data – 10 points Quality of Participant-generated preliminary data and demonstrated potential success Manufacturing Considerations – 10 points Scalability and cost-effectiveness of manufacturing 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) 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