Characterization of Islet-derived Extracellular Vesicles for Improved Detection, Monitoring, Classification, and Treatment of Type 1 Diabetes (R01 Clinical Trial Not Allowed) | RFA DK 21 016

Opportunity Information: Apply for RFA DK 21 016

The NIH funding opportunity RFA-DK-21-016, titled "Characterization of Islet-derived Extracellular Vesicles for Improved Detection, Monitoring, Classification, and Treatment of Type 1 Diabetes (R01 Clinical Trial Not Allowed)," supports research aimed at understanding and leveraging extracellular vesicles (EVs) that originate from the human pancreatic islet and the surrounding pancreatic tissue environment. The core idea is to build better ways to isolate, purify, and thoroughly characterize these vesicles in people who are healthy, people who already have type 1 diabetes (T1D), and people who are at increased risk of developing T1D. By improving the technical and experimental toolkit around pancreatic/islet-derived EVs, the program is trying to open up a clearer view into what is happening in the pancreas during health, early immune attack, and established disease.

A major emphasis of the initiative is platform and method development: applicants are expected to propose robust tools, workflows, and experimental systems that can reliably capture and analyze EVs that truly come from islet cells (and not just a generic mixture of vesicles from the bloodstream or other tissues). This includes efforts to define EV composition (such as proteins, lipids, and nucleic acids), identify markers that distinguish islet-origin EVs from other EV populations, and standardize approaches so results can be compared across studies. Because EVs are small, heterogeneous, and easily confounded by contaminants, the spirit of the announcement is to push beyond basic EV measurements and into more precise, reproducible, and biologically interpretable characterization.

Beyond the technical focus, the opportunity also supports studies that examine what pancreatic EVs do biologically and how they might contribute to islet function, islet stress, immune interactions, and the earliest stages of T1D initiation. That includes investigating whether EVs participate in signaling pathways that reflect beta cell injury, inflammation, or immune activation, and whether changes in EV cargo or abundance track with progression from at-risk states to overt diabetes. The program is interested in how EV biology relates to both normal islet physiology and the dysfunction that occurs as T1D develops.

Another central goal is translational in nature: developing EV-based diagnostic approaches that could improve disease monitoring and classification. In practical terms, this means exploring whether islet-derived EV signatures can serve as biomarkers to help detect islet stress earlier, distinguish different disease trajectories, monitor ongoing beta cell destruction, or stratify individuals into more informative categories than current clinical measures allow. The announcement also points to the possibility of using insights from pancreatic EV biology to identify new therapeutic targets, meaning EV-related pathways, EV cargo, or EV-mediated communication mechanisms that could be manipulated to preserve islet function or alter disease progression. Even though therapeutic target discovery is within scope, the FOA is explicitly an R01 mechanism with "Clinical Trial Not Allowed," so the funded work is intended to be preclinical, mechanistic, and/or technology-driven rather than interventional clinical testing.

In terms of administrative details, this is a discretionary NIH grant using the R01 research project mechanism, within the health-related activity area (CFDA 93.847). The award ceiling listed is $500,000, and the original closing date was 2021-11-03, with the funding opportunity created on 2021-06-03. The sponsoring agency is the National Institutes of Health, and the topic aligns closely with NIH efforts to improve understanding, detection, and management of diabetes through advanced biomarker and mechanism research.

Eligibility is broad across U.S.-based organizations and includes state, county, city/township, and special district governments; public and state-controlled institutions of higher education; private institutions of higher education; independent school districts; and public housing authorities/Indian housing authorities. Eligible applicants also include federally recognized Native American tribal governments and other Native American tribal organizations (including those other than federally recognized tribal governments), as well as nonprofits (both 501(c)(3) and non-501(c)(3)), for-profit organizations (other than small businesses), and small businesses. The FOA explicitly highlights additional eligible applicant types such as Alaska Native and Native Hawaiian Serving Institutions, Asian American Native American Pacific Islander Serving Institutions (AANAPISIs), Hispanic-serving Institutions, Historically Black Colleges and Universities (HBCUs), Tribally Controlled Colleges and Universities (TCCUs), faith-based or community-based organizations, eligible federal agencies, regional organizations, and U.S. territories or possessions.

Foreign eligibility is restricted in a specific way: non-domestic (non-U.S.) entities and non-domestic components of U.S. organizations are not eligible to apply as the applicant organization. However, "foreign components" are allowed as defined by the NIH Grants Policy Statement, meaning a U.S. applicant may include certain foreign collaborations or performance sites if they meet NIH’s definition and justification requirements. In short, the application must be led by an eligible domestic organization, but carefully structured international collaboration can still be part of the project when appropriate and properly documented.

Overall, the opportunity is designed to accelerate the field toward reliable, islet-specific EV isolation and profiling methods, then use those advances to clarify how EVs reflect and influence T1D biology, and finally translate that knowledge into better biomarker strategies and new therapeutic hypotheses. The program is focused on building foundational capabilities and mechanistic understanding that could later support clinical validation studies or therapeutic development, even though those clinical trials themselves are outside the scope of this particular R01 call.

• The National Institutes of Health in the food and nutrition, health sector is offering a public funding opportunity titled "Characterization of Islet-derived Extracellular Vesicles for Improved Detection, Monitoring, Classification, and Treatment of Type 1 Diabetes (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 2021-06-03.
• Applicants must submit their applications by 2021-11-03. (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.
• 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 21 016

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