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Problem
Many human diseases are driven by RNA dysfunction or by difficult-to-drug proteins, making them challenging to treat with existing approaches. While RNA has often been used as a treatment for disease, it has rarely been utilized directly as a therapeutic target to address unmet medical needs.
About the Challenge
The National Institutes of Health (NIH) has launched the Targeting RNA in Disease with Novel Technologies (TRDNT) Challenge to spur the development, validation, and dissemination of novel technologies that target RNA in human disease. TRDNT is the latest initiative from NIH's Common Fund Venture Program, supporting short-term projects with long-term impact across NIH Institutes, Centers, and the Office of the Director.
The Goal
This challenge is intended to spur the development, validation, and dissemination of a publicly available suite of novel RNA-targeting technologies for new therapeutic classes, leading to the development of precision RNA-targeting therapies to treat diseases linked to RNA dysfunction or driven by difficult-to-drug proteins, which may be addressed upstream at the RNA level.
In Phase II (Prototype Development and Use Case Demonstration), participants will:
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Design a solution that provides an initial prototype RNA-targeting technology
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Provide an example use case of how this technology can be used to target a human disease-relevant RNA target
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Demonstrate that it can be elaborated into a publicly accessible technology in Phase III
$13.1 Million - Total Prize Purse
Phase I - Closed
$500K
Phase II
Up to $7.8 Million
Phase III
Up to $4.8 Million
*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.
Before You Apply
TRDNT is intended for novel technologies that target endogenous RNA to treat disease. This challenge is not focused on standard RNA-based therapeutic programs unless the proposed approach specifically targets endogenous RNA in a way that aligns with the challenge goals.
Applicants need to carefully review the official rules before preparing a submission.
Strong submissions for Phase II: Stage I are expected to:
• Focus on technologies that target endogenous RNA
• Present a novel and innovative approach
• Show relevance across multiple diseases
• Demonstrate a clear path toward prototype development
• Follow the official rules and submission guidance closely
Only solutions that target endogenous RNA to treat disease will be considered competitive for this Challenge.
Who Should Consider This Challenge
If you are a US-based researcher, innovator, or organization developing new ways to target endogenous RNA in human disease, this challenge is for you. This includes: teams of individuals, startups, small or mid-size businesses, large businesses, non-profit organizations, and academic or independent research institutions.
Some examples may include:
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Academic researchers and translational labs
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Teams exploring RNA small molecule, RNA structure, spliceosome, ribosome, or RNA protein interaction approaches
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Biotech founders and early-stage companies
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University technology transfer and commercialization teams
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SBIR and STTR-aligned innovators
We encourage broad participation from diverse institutions, regions, and technical backgrounds.
What NIH is Looking For
Competitive submissions should present innovative technologies that modulate RNA in human disease and could support the development of new therapeutic classes. Approaches may include, but are not limited to:
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Technologies that modify RNA-RNA binding protein (RBP) interactions to modulate splicing, stability, or translation
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Methods to target long non-coding RNAs (lncRNAs) to regulate gene expression
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Novel assays to identify native RNA-protein interactions and examine therapeutic effects
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Screening libraries designed and validated to be enriched with RNA-targeting small molecules
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Technologies that modify aberrant RNA structures for therapeutic purposes
Submissions are not to be limited to these examples, but they must align with the challenge goal of targeting endogenous RNA in disease.
How the Challenge Works
Phase I: Planning Comprehensive RNA-Targeting Technologies
CLOSED
Participants propose a novel RNA-targeting technology and explain how it could be developed into a prototype.
Prizes
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Up to $20,000 per winner
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25 winners maximum
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Winners will be announced: September 2026.
Phase II: Prototype Development and Use Case Demonstration
Interim Milestones Coming Soon
The goal of this Phase of the Challenge is to: design a solution that provides an initial prototype RNA-targeting technology, including an example use case of how this technology can be used to target a human disease-relevant RNA target, that can be elaborated into a publicly accessible technology in Phase III.
Only complete submissions will be reviewed.
Interim milestone prizes will be awarded based on participants' progress and continued commitment to their prototype technology and putting it to use to develop new RNA-targeting therapies for human disease.
Interim milestone open to Phase I winners and qualified new entrants. Only interim submission winners are eligible to apply for the final submission in Phase II: Stage II.
Prizes
Timeline
- Interim Milestone: Up to $120,000 per winner
- 25 winners maximum
- Final Submission: Up to $320,000 per winner
- Only Phase II Interim Milestone winners eligible
- 15 winners maximum
Phase II Launch: August, 2026
Interim Milestone
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Submission Window: December 1st, 2026 - February 1st 2027
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Judging: February - March 2027
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Winners Announced: March 2027
Final Submission (Only Phase II Winners eligible)
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Launch: March 2027
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Submission Window: July – August 2027
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Judging: August - September 2027
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Winners Announced: October 2027
Phase III: Final Iteration and Technology Dissemination
Open to Phase II final winners only.
Participants validate their technology and finalize a plan to make it publicly available to the scientific community.
Prizes
- Winners: Up to $525,000
- 8 winners
- Runners-Up: Up to $200,000
- 3 winners maximum
Timeline (Anticipated)
- Phase III Launch: November 2027
- Submission Window: August – October 2028
- Winners Announced: January 2029
*All dates are subject to change. Future phase timelines are anticipated and contingent upon NIH discretion.
Getting Ready for Phase II
Phase II: Prototype Development and Use Case Demonstration - Open to all participants, Phase I participation not required.
Phase II participants are required to submit:
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Evidence of the initial development of the prototype RNA-targeting technology
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Provide an example via use case of how this technology can be used to target a human disease-relevant RNA target
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Include metrics of success and efficacy in treating human disease
Participants will also be responsible for providing a detailed public access and dissemination plan (PADP) to illustrate how the technology will be made publicly available and include the preliminary recruitment of an external partner to enable this dissemination.
Phase II of this Challenge is separated into two Stages:
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Stage I: Interim submissions for milestone delivery
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Stage II: Final Phase II submissions (open to Phase II: Stage I interim milestone winners only, full details to be announced at a later date)
To be highly competitive in this challenge, solutions must:
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Address RNA targets that can affect multiple diseases
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Address unmet medical needs in the RNA-targeting space and document a use-case for early-stage validation of the technology
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Be innovative and novel in approach, with avoidance of well-established and widely utilized technologies
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Have the appropriate expertise and environment to support the development and effective testing of the technology
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Outline a clear PADP to inform on public access plans for the technology
How To Participate
Applicants should read the full challenge announcement, rules, and submission guidance before preparing an application.
Key requirement: Winning technologies must be made publicly available. Participants should plan from the outset for open dissemination of their technology to the scientific community.
Have questions? Visit our live FAQ page to find answers to common questions about challenge eligibility, submissions, and timeline.
Submissions opening this December.
Get started on your Phase II: Stage I application before it opens
View the Interim Milestone submission format, requirements, and judging criteria here.
Phase II: Stage I Applications Opening Soon!
Be first in line when Phase II applications open.
Stay Informed
Interested participants are encouraged to review the official rules and scope to determine whether their technology is a fit for the TRDNT Challenge.
Visit the official NIH challenge page for rules and updates.
For questions, contact the challenge team at info@trdntchallenge.com.