Engineering Improved Stem Cell-Derived Islet Cells for Replacement Therapies (R01 - Clinical Trial Not Allowed) | RFA DK 26 306

Opportunity Information: Apply for RFA DK 26 306

The National Institutes of Health (NIH), through a Notice of Funding Opportunity (NOFO) titled "Engineering Improved Stem Cell-Derived Islet Cells for Replacement Therapies (R01 - Clinical Trial Not Allowed)" (Funding Opportunity Number RFA-DK-26-306), is soliciting research proposals that focus on making stem cell-derived islet cell products intrinsically better suited for cell replacement therapies, particularly in the context of type 1 diabetes. The core idea is that stem cell-derived products, unlike cadaveric human islets, come from standardized and tightly controlled cell bank sources. Because these products can be banked, manufactured, and quality-tested under highly defined conditions, investigators have a unique opportunity to deliberately build in traits that make the transplanted cells more resilient, longer-lasting, and better functioning once implanted. The NOFO is oriented toward understanding what intrinsic properties matter most for durable graft performance and how those properties can be engineered in a rational, testable way.

A major emphasis of the opportunity is on identifying and validating targets, mechanisms, and pathways that are realistically "engineerable" during the development and manufacturing lifecycle of stem cell-derived islet cell products. This can include strategies that alter cell-intrinsic biology to improve survival, function, and durability in the transplant setting, rather than relying solely on external devices, systemic drugs, or supportive co-therapies. The NOFO also explicitly encourages rigorous preclinical testing and validation, meaning applicants should be prepared to show how their engineering approach translates into measurable improvements in graft viability and islet function in relevant models. While the announcement does not enumerate specific experimental approaches in the provided text, the intent is clear: move beyond describing problems and instead develop actionable engineering interventions that can be incorporated into a controlled manufacturing and quality control pipeline for stem cell-derived islet products.

This NOFO is tied to the congressionally established Special Diabetes Program, which supports research aimed at preventing, treating, and curing type 1 diabetes and its complications. In practice, that connection signals that the work supported here is expected to be strongly aligned with translational goals that can ultimately improve replacement therapies for people with type 1 diabetes, while still remaining within a preclinical research scope. Consistent with the title, the R01 mechanism is being used, and clinical trials are not allowed under this particular opportunity, so the supported work should not be structured as a clinical intervention study in human participants.

From an administrative and eligibility standpoint, the opportunity is categorized as discretionary grant funding in the health area (CFDA 93.847). A wide range of U.S.-based applicant types are listed as eligible, including state, county, and local governments; tribal governments and tribal organizations; public and private institutions of higher education; nonprofit organizations (both 501(c)(3) and non-501(c)(3)); for-profit organizations (other than small businesses); and small businesses, among others. The awarding agency is NIH, and the program is associated with NIDDK given the RFA-DK identifier and the diabetes focus.

There are strict limits on international participation. Non-U.S. entities are not eligible to apply, and non-U.S. components of U.S. organizations are also not eligible. Foreign components, as defined by NIH policy, are not allowed under this NOFO. In addition, NIH policy effective May 1, 2025, is highlighted: NIH will not issue awards that involve foreign subawards or subcontracts unless the application is submitted to a NOFO specifically designated for funded international collaborations. As a result, any application to this NOFO that includes a foreign subaward or subcontract will be considered noncompliant and will not be reviewed for funding. At the same time, the policy statement clarifies that this does not necessarily rule out all forms of international interaction; it does not preclude unfunded international collaborations, foreign consultants, or purchasing unique equipment or supplies from foreign vendors, as long as the arrangement does not constitute a foreign subaward/subcontract or an impermissible foreign component.

Key practical details include an original closing date of March 7, 2026, an award ceiling of $500,000, and an expectation of about 6 awards. Taken together, this is a targeted NIH R01 opportunity aimed at advancing the science and engineering needed to produce stem cell-derived islet cell therapies with improved intrinsic robustness, with the near-term focus on preclinical evidence that engineered cell properties can meaningfully improve transplant outcomes.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "Engineering Improved Stem Cell-Derived Islet Cells for Replacement Therapies (R01 - Clinical Trial Not Allowed)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.847.
• This funding opportunity was created on 2025-12-03.
• Applicants must submit their applications by 2026-03-07. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
• Each selected applicant is eligible to receive up to $500,000.00 in funding.
• The number of recipients for this funding is limited to 6 candidate(s).
• Eligible applicants include: State governments, County governments, City or township governments, Special district governments, Independent school districts, Public and State controlled institutions of higher education, Native American tribal governments (Federally recognized), Public housing authorities/Indian housing authorities, Native American tribal organizations (other than Federally recognized tribal governments), Nonprofits having a 501 (c) (3) status with the IRS, other than institutions of higher education, Nonprofits that do not have a 501 (c) (3) status with the IRS, other than institutions of higher education, Private institutions of higher education, For-profit organizations other than small businesses, Small businesses, Others.

Apply for RFA DK 26 306

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