Overview

The National Institutes of Health (NIH) Common Fund announces the “Targeting RNA in Disease with Novel Technologies (TRDNT)” Challenge – Phase I. TRDNT is the latest initiative from NIH’s Venture Program, which supports short-term projects with long-term impact. The Common Fund Venture Program is a new area of Common Fund support that provides a framework for development of short-term Common Fund initiatives that embrace bold approaches and are responsive to the shared priorities of NIH Institutes, Centers, and the Office of the Director. The goal of this Challenge is to spur the development, validation and dissemination of a publicly available suite of novel RNA-targeting technologies for new therapeutic classes that can lead to the development of precision RNA-targeted therapies to treat diseases that are either (1) caused by difficult to drug protein targets (proteins unlikely to be modulated with a small molecule) that could be treated upstream at the RNA level or (2) for diseases that at this time are incurable but have roots in RNA dysfunction.

The total prize purse from NIH for Phase I of this Challenge is up to $500,000. NIH envisions building upon Phase I and launching two subsequent Phases to award additional cash prizes of up to $12,600,000 for a total planned cash prize purse of $13,100,000, distributed over distinct Phases as shown below. However, announcement of additional phases and prizes of this Challenge is at the discretion of NIH and contingent upon the availability of appropriated funds from which payment for this purpose can be made.

• Phase I: Planning Comprehensive RNA-Targeting Technologies – $20,000 per winner, up to 25 winners.
• Phase II*: Prototype Development and Use Case Demonstration – (Open to all Participants, Phase I participation not required)
• Interim Milestone: up to $120,000 per winner, up to 25 winners.
• Final Phase II Submission: up to $320,000 per winner, up to 15 winners
• Phase III*: Final Iteration and Technology Dissemination (Open to Phase II final winners only) - up to $525,000 per winner, up to 8 winners.
• Runner-up: up to $200,000 per winner, up to 3 winners.

*Phases II and III would be launched by way of one or more announcements that describe requirements and registration, as well as final prize amounts.

Subject of the Challenge

It is estimated that only ∼1.5% of the human genome encodes ∼21,000 distinct protein-coding genes and that most of the genome is transcribed into RNA. While RNA has often been used as a treatment for disease, RNA has rarely been utilized as a therapeutic target. Recent advances have indicated that RNA can be leveraged as a target to treat diseases not only caused as a direct result of RNA dysfunction but also diseases in which a difficult to drug protein is causative. RNA also has the potential to be targeted in several forms, providing multiple target options for disease treatment, with some examples listed below:

• Targeting transfer RNA (tRNA) and messenger RNA (mRNA): tRNAs and mRNAs can become dysregulated in many diseases, including several neurological disorders and rare diseases, causing disruption of the translation of mRNA into a protein.
• Targeting long non-coding RNA (lncRNA): a large class of RNA transcripts, many with established regulatory functions
• Targeting micro-RNA (miRNA): small non-coding RNAs that regulate the expression of protein-coding and other genes
• Targeting PIWI protein-binding RNAs (piRNAs): piRNAs are also targetable and have many regulatory functions, including within the pretranscriptional, transcriptional, posttranscriptional, and translational steps.
• Targeting pre-mRNA and the spliceosome: the spliceosome functions as a catalyst for the removal of introns from nuclear pre-mRNA, and modulation of spliceosome function could reveal new ways to treat intractable diseases, such as Huntington’s disease.
• Targeting Ribosomes: ribosomes, made of both RNA and protein, are primary protein synthesis machines whose dysregulation have been implicated in a variety of diseases including bacterial infection and cancer. Unlike specific classes of RNAs, where the effort has been focused on targeting secondary structure elements, the ribosome is unique in that it presents many vast and highly expansive targetable binding pockets that could accept small molecules.

Ultimately, RNAs are an important emerging target class for the development of therapeutics, and progress in the development of RNA-targeting technologies should provide exciting future possibilities.

The goal of this Challenge is to develop, validate and disseminate a publicly available suite of novel RNA-targeting technologies for new therapeutic classes that can lead to the development of precision RNA-targeted therapies to treat diseases that are either (1) caused by difficult to drug protein targets (proteins unlikely to be modulated with a small molecule) that could be treated upstream at the RNA level or (2) for diseases that at this time are incurable but have roots in RNA dysfunction.

To address the need for RNA-targeting therapeutics, the Challenge focuses on developing novel and innovative technologies that modulate RNAs in human disease, such as:

• Approaches to modify RNA-RNA binding protein (RBP) interactions to modulate splicing, stability or translation;
• Targeting long non-coding RNAs (lncRNAs) to regulate gene expression in cis or trans (nearby vs. distant genes, respectively);
• Novel assays to identify native RNA-RBP interactions and examine therapeutic effects;
• Design and validate screening libraries that are enriched with RNA-targeting small molecules;
• Approaches that modify aberrant RNA structures for therapeutic purposes.

These are only examples, and submissions need not be limited to the above.

Only solutions that target endogenous RNA to treat disease will be considered competitive for this Challenge.

This Challenge is separated into three phases. At this time, NIH is launching Phase I only. NIH is considering launching Phases II & III at a later date and provides the anticipated details of those phases here for the awareness of Phase I participants. However, announcement of additional phases of this Challenge is at the discretion of NIH and contingent upon the availability of appropriated funds from which payment for this purpose can be made.

Phase I: Planning Comprehensive RNA-Targeting Technologies – During this Phase, Participants will design an RNA-targeting therapeutic technology that can be elaborated into a working prototype in the second stage of the Challenge. Participants are required to submit a solution proposal, which must include (1) a description of how their technology will address a significant health need in the patient community, (2) early stage technical concept for how the technology will target RNA and provide a framework for developing novel treatments, and (3) detailed plan to outline how the Participant will carry out development and use case demonstration of the technology. Participants must submit all of the above to be eligible to win Phase I of this Challenge.

To be highly competitive in this Challenge, solutions must:

• Address RNA targets across multiple diseases.
• Address unmet medical needs in the RNA-targeting space.
• Be innovative and novel in approach, with avoidance of well-established and widely utilized technologies.
• Have the appropriate expertise and environment (or the ability to quickly acquire the relevant resources and expertise) to support the development of proposed technology in future Phases.
• Identify potential roadblocks and suggest additional expertise or alternative methods to facilitate roadblock resolutions.

Phase II: Prototype Development and Use Case Demonstration – (Open to all Participants, Phase I participation not required) Participants submitting to this Phase are required to submit evidence of the initial development of the prototype RNA-targeting technology and provide an example via use case of how this technology can be used to target a human disease relevant RNA target as well as include metrics of success and efficacy in treating human disease. It will also be expected that Participants provide a detailed dissemination plan to illustrate how the technology will be made publicly available and include the preliminary recruitment of an external partner to enable this dissemination.

Phase III: Final Iteration and Technology Dissemination – in the final phase of the Challenge, Participants are required to submit the final, validated version of their technology, as well as their finalized plan for ensuring their technology is publicly available at time of prize payment. Only Phase II final winners are eligible to submit to Phase III.

All Phase winners are encouraged to apply for NIH funding to continue development of their technologies, but such funding is not guaranteed and is subject to the standard competition and application requirements of the relevant funding opportunity announcements.

Pre-Submission Webinar: The TRDNT Challenge intends to hold a Pre-Submission Webinar for all interested prospective participants. Webinar date and other details will be posted on the TRDNT Challenge website: https://commonfund.nih.gov/venture/trdnt.

Prospective Dates

• Challenge Launch: March 2026
• Phase I: Planning Comprehensive RNA-Targeting Technologies
  • Submission Start/End: May/June 2026
  • Judging Start/End: July/August 2026
  • Winners Announced: August 2026

At the discretion of NIH, additional phases of the Challenge may follow Phase I. Future phases, if launched, are anticipated to run on the following timeline, which may be subject to change:

• Phase II: Prototype Development and Use Case Demonstration (anticipated)
  • Launch: August 2026
  • Milestone Submission Start/End: November 2026/January 2027
  • Milestone Judging Start/End: January/February 2027
  • Milestone Winners announced: March 2027
  • Main Phase Submission Start/End: June/July 2027
  • Judging Start/End: August/September 2027
  • Winner Announced: October 2027
• Phase III: Final Iteration and Technology Dissemination (anticipated)
  • Launch: November 2027
  • Submission Start/End: August/October 2028
  • Judging Start/End: November/December 2028
  • Winner Announced: January 2029

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 Initiatives, 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 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.

Prizes

Amount of the Prize:

The total prize purse for Phase I of this Challenge is up to $500,000. NIH envisions building upon Phase I and launching two subsequent Phases to award additional cash prizes of up to $12,600,000 for a total planned cash prize purse of $13,100,000, distributed over distinct Phases as shown below. However, announcement of additional phases and prizes of this Challenge is at the discretion of NIH and contingent upon the availability of appropriated funds from which payment for this purpose can be made.

Prizes will be awarded following the successful completion of Phase I and each anticipated subsequent phase of the Challenge in the following amounts:

• Phase I: Planning Comprehensive RNA-Targeting Technologies – up to $20,000 per winner, up to 25 winners.
• Phase II: Prototype Development and Use Case Demonstration (anticipated) – prizes may be disbursed across the following stages within the Phase:
  • Interim Milestone: up to $120,000 per winner, up to 25 winners.
  • Final Phase II Submission: up to $320,000 per winner, up to 15 winners.
• Phase III: Final Iteration and Technology Dissemination (anticipated, Open to Phase II final winners only) – up to $525,000 per winner, up to 8 winners.
  • Runner-up: up to $200,000 per winner, up to 3 winners.

Prize funds that remain unawarded after the selection of winners for each phase may be rolled over into a subsequent phase and added to those prize payments; however, any decision to increase any individual prize amounts from what is outlined above is entirely at the discretion of the NIH.

Award Approving Official:

The Award Approving Official will be the (Acting) Director of the Division of Program Coordination, Planning, and Strategic Initiatives within the NIH Office of the Director, or as otherwise delegated.

Payment of the Prize:

Prizes awarded under this Challenge will be paid by electronic funds transfer and may be subject to federal income taxes. The Department of Health and Human Services (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.

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 Rules

To be eligible to win a prize under this Challenge, a Participant (whether participating as a Team or Entity):

1. Shall have registered to participate in the Challenge under the rules promulgated by the National Institutes of Health (NIH) as published in this announcement;
2. Shall have complied with all the requirements set forth in this announcement;
3. In the case of a private entity, shall be incorporated in and maintain a primary place of business in the United States, and in the case of an individual, whether participating singly or in a group, 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 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, if applicable, may be recognized when the results are announced.
4. Shall not be a federal entity or federal employee acting within the scope of their employment;
5. 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;
6. 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;
7. 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, step-parent, child, or step-child).
8. Shall be 18 years of age or older at the time of submission.

Participation Rules

1. 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.
2. 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.
3. By participating in this Challenge, each Participant (whether participating as a Team or 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.
4. 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 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.
5. A Participant (whether participating as a Team or 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.
6. By participating in this Challenge, each Participant (whether participating as a Team or 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.
7. By participating in this Challenge, each Participant (whether participating as a Team 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 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.
8. Each Participant (whether participating as a Team or Entity) agrees to follow all applicable federal, state, and local laws, regulations, and policies.
9. Each Participant (whether participating as a Team or 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.
10. As a condition for winning a cash prize in this Challenge, each Participant (whether participating as a Team or Entity) that has been selected as a winner must complete and submit all requested winner verification and payment documents to NIH within 10 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.

Judging Criteria

Basis Upon Which a Winner Will be Selected

Phase I: Planning Comprehensive RNA-Targeting Technologies: A panel of technical experts with subject matter expertise directly relevant to the Challenge goals will evaluate Phase I submissions based on their ability to fulfill the criteria listed below. The Phase I winners will be selected by a panel of federal employees serving as competition judges, which may include NIH program staff, subject to the final decision by the Award Approving Official.  

Phase I Evaluation Criterion - the review will consider:

• Completeness of the information requested in the fulfillment of the Phase I submission requirements – 10 points
• Potential clinical impact of solution – 30 points
  • How well does the solution address unmet medical needs in the RNA-targeting space?
  • To what extent is the technology likely to address multiple disease areas or classes of diseases?
• Novelty of the proposed solution – 30 points
  • How comprehensive and innovative is the proposed technology?
  • How comprehensive is the amount of detail provided in the technical concept and is it enough to determine if the technology could be successfully prototyped in future Phases of the Challenge?
• Likelihood that Participant can carry out development of the technology – 30 points
  • How feasible and straightforward is the proposed workflow?
  • To what degree does the team represent an appropriate group of innovators with the ability to tackle the proposed problem?
  • To what degree and how well has the Participant outlined their plan to ensure appropriate expertise and environment are available to support the development of proposed technology?
  • To what degree does the Participant identify potential roadblocks and suggest additional expertise or alternative methods they would utilize to facilitate resolutions?

Phase II Evaluation Criterion [anticipated] – (Open to all Participants) the review will consider the RNA-targeting technology prototype design and how well the submitted use case provides evidence that this technology can be used to target human disease relevant RNA targets. The detailed dissemination plan will also be considered by reviewers, and solutions will be evaluated on how well the plan illustrates how the technology will be made publicly available, including early support from and relevance of proposed external partners to enable this dissemination. To support Participants’ continued participation in this Phase of the Challenge, interim milestone prizes will be awarded based upon each Participant’s demonstration of substantial efforts toward furthering the development of their prototype technology (i.e., progress towards a functional prototype and achieving a viable use case) and their continued commitment to implementing their technology in order to facilitate the development of novel RNA-targeting therapeutic technologies for treating human disease. Specific evaluation criteria will be provided when Phase II of the Challenge is announced.

Phase III Evaluation Criterion [anticipated] – (Only Phase II final winners are eligible for submission to Phase III) the review will consider the final design of the technology, to include (1) a final modification/improvement report based on feedback from reviewers in previous Phases, (2) a validation report, and (3) a finalized plan for ensuring their technology is publicly available at time of prize. Specific evaluation criteria will be provided to final winners from Phase II when Phase III of the Challenge is announced.

How to Enter

Registration Process: The official announcement for the Targeting RNA in Disease with Novel Technologies (TRDNT) Challenge – Phase I can be found on a publicly-accessible government website at www.nih.gov/challenges. Further information about the Challenge registration and submission portal will be provided closer to the submission start date.

To register, Participants will first be directed to establish an account in the submission portal (details will be provided closer to the submission start date). Participants will be required to identify whether they are registering as either of the following: as an independent 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). Participants will need to provide the name, affiliation, and contact information of all individuals competing in this Challenge as part of a Team or on behalf of an Entity. All Participants will also be required to acknowledge whether federal funding will be used in the development of the Challenge submission (see Participation Rule 1). All Participants must certify they have read, understand, and agree to abide by the official eligibility rules, participation rules, and requirements for the Challenge as stated in this announcement.

• For Teams: Each participating Team is required to identify a Team Captain who will register and submit on behalf of the Team members. The Team Captain 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 Captain must be a citizen or permanent resident of the United States. In the event that a dispute regarding the identity of the Team Captain 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 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 I: Planning Comprehensive RNA-Targeting Technologies – the focus of Phase I is to design an RNA-targeting therapeutic technology that can be elaborated into a working prototype in the second Phase of the Challenge. This solution is expected to address an unmet need in the RNA-targeting space that is relevant across multiple human diseases, be comprehensive and innovative in design, and provide sufficient detail to indicate that the submitting Participant has the skills and resources necessary (or can acquire them quickly) to develop the proposed technology.

Once Participants have completed the registration step and established an account in the online submission portal at the link above, they must provide the following as their formal submission:

1. Title and Executive Summary, the latter of which should include a brief description of the technology and how it will help to develop novel RNA-targeted therapies across multiple diseases. Do not include any proprietary or confidential information in the Title and Executive Summary sections as they may be publicly shared if the Participant is selected to win a prize across any Phase of this Challenge (see Participation Rule 7).
2. Description of how the technology will address a significant health need in the patient community, including a description of the potential impact of the solution on the development of novel RNA-targeting therapies.
3. Early stage technical concept for how the technology will target RNA and provide a framework for developing novel treatments. This must include sufficient details to illustrate that the proposed technology can be successfully prototyped in Phase II.
4. Detailed plan to outline how the Participant will carry out development and use case demonstration of the technology. This must include a description of the Participant expertise and environment, as well as a summary of potential roadblocks to development and resolutions or expertise needed to address them. This section must also include sufficient detail to indicate that the submitting Participant has the skills and resources necessary (or can acquire them quickly) to develop the proposed technology.

Participants must submit all of the above to be considered for a prize in Phase I of this Challenge.

All submissions must follow the format and instructions described below.

• Consist of a single PDF file with page size set to 8.5” x 11” and at least 1-inch margins.
• Use a font no smaller than 11-point Arial and line spacing no less than 1.0.
• Be written in English.
• Adhere to any page length requirements as stipulated in the submission portal.
• Not use the HHS logo or official seal or the logo of NIH or NIA in the entries and must not claim federal government endorsement.

For Phase I, Participants must complete their submission and provide all of the requested information in the portal no later than 11:59 PM Eastern Time on the submission deadline. Participants who do not submit their complete submission via the portal by this deadline will not have their submission considered for this Challenge. 

Phase II: Prototype Development and Use Case Demonstration [anticipated] – the focus of Phase II will be to build an initial prototype of an RNA-targeting technology and demonstrate evidence that this technology can be used to target human disease relevant RNA-targets through a real-world use case. The solution will require clear success metrics and will provide the opportunity for interim milestone prizes for Participants able to demonstrate substantial efforts toward furthering the development of their prototype technology. Specific submission requirements will be provided when Phase II of the Challenge is announced.

Phase III: Final Iteration and Technology Dissemination [anticipated] – the focus of Phase III will be the final development of a validated technology and dissemination of this technology to the scientific community. Only those Participants that have been selected as final winners of Phase II will advance to Phase III of the Challenge.

Contact

For Further Information Contact: trdnt@od.nih.gov

Winners

Winners will be announced following judging of submissions.