Trans-Agency Blood-Brain Interface Program (R61/R33 - Clinical Trials Not Allowed) | RFA HL 20 021

Opportunity Information: Apply for RFA HL 20 021

The Trans-Agency Blood-Brain Interface Program (R61/R33 - Clinical Trials Not Allowed) is an NIH grant opportunity designed to push forward high-risk, high-reward research focused on the blood and vascular side of the blood-brain interface, commonly referred to as the blood-brain barrier (BBB). The central goal is to improve how the field models the human BBB by supporting the creation of enhanced or modified experimental platforms that better reflect how the human BBB behaves in both healthy (normal) and disease (pathological) conditions. Rather than treating the BBB only as a layer of brain-associated cells, this program emphasizes that the BBB is shaped in a major way by blood-derived and vascular factors, and it aims to build model systems that capture that reality.

A major theme of the FOA is redefining and expanding the classic concept of the neurovascular unit by explicitly incorporating the blood/vascular component into what is described as the neurovascular-blood unit. In practical terms, the program is looking for research that does more than model endothelial cells alone. It encourages studies and platform development that incorporate, or are strongly informed by, dynamic interactions between vascular biology and circulating blood elements. Proposals that examine how vascular, hemostatic (clotting-related), hematopoietic (blood-forming), and immune cells interact with and regulate the blood-brain interface are specifically called out as being of particular interest. The intent is to catalyze a new or expanded field of science where BBB modeling better captures real human physiology, including the influence of blood components that can change rapidly during inflammation, injury, infection, neurodegeneration, or systemic disease.

The program is structured as an R61/R33 mechanism, which generally supports a phased approach: an early, milestone-driven stage intended to establish feasibility and demonstrate proof-of-concept (R61), followed by a second stage aimed at further development and validation once predefined milestones are met (R33). Although the detailed milestone requirements are not provided in the text you shared, the overall spirit of the mechanism aligns with the FOA's emphasis on ambitious platform-building and transformative methods, where early success criteria determine whether the project moves into the next phase. Clinical trials are not allowed under this opportunity, which signals that the work should remain in the preclinical and translational research space, such as human cellular systems, advanced in vitro models, organ-on-chip approaches, engineered microphysiological systems, or other non-clinical platforms intended to complement existing animal-model-based research.

In terms of impact, NIH frames this initiative as a way to create next-generation preclinical human cellular model systems of the BBB that can sit alongside animal models and potentially address some of their limitations. Better human-relevant BBB platforms can help researchers study mechanisms of BBB dysfunction, investigate how immune and blood factors influence brain health, and improve screening or evaluation of therapeutics that must cross or modulate the BBB. By focusing on the blood/vascular components and their regulation, the program is also implicitly encouraging models that can capture systemic-to-brain signaling and the ways peripheral events may alter BBB integrity, transport, inflammation, and vascular homeostasis.

The opportunity is listed as discretionary funding through the NIH under a grant funding instrument and a health-related activity category, associated with CFDA numbers 93.233, 93.837, 93.838, 93.839, and 93.840. The Funding Opportunity Number is RFA-HL-20-021, and the Agency Name is the National Institutes of Health. The source information provided lists an award ceiling of $425,000 and notes an original closing date of 2021-12-21, with a creation date of 2019-09-03.

Eligibility is broad across U.S.-based organizations and includes many government entities (state, county, city/township, and special district governments), independent school districts, public and state-controlled institutions of higher education, private institutions of higher education, federally recognized tribal governments, and tribal organizations that are not federally recognized. It also includes public housing authorities/Indian housing authorities, nonprofits with or without 501(c)(3) status (as long as they are not institutions of higher education), for-profit organizations (other than small businesses), and small businesses. The FOA additionally highlights eligibility for a range of mission- and community-centered institutions 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, regional organizations, eligible federal agencies, and U.S. territories or possessions.

At the same time, the FOA draws clear lines around foreign participation. Non-domestic (non-U.S.) entities and foreign institutions are not eligible to apply as applicant organizations, and non-domestic components of U.S. organizations are not eligible to apply. However, foreign components are allowed as long as they fit NIH's definition in the NIH Grants Policy Statement. This typically means a U.S. applicant can include certain international collaborations or activities as a foreign component when scientifically justified, even though a foreign institution cannot be the primary applicant.

Overall, this grant opportunity is aimed at teams willing to take bold, platform-oriented scientific risks to create more human-relevant BBB model systems by explicitly integrating the blood and vascular context. The program seeks to shift the field toward an expanded blood-brain interface framework, encouraging researchers to build models that reflect not only brain-side cellular architecture but also the circulating and vascular forces that regulate BBB function in health and disease.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "Trans-Agency Blood-Brain Interface Program (R61/R33 - Clinical Trials Not Allowed)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.233, 93.837, 93.838, 93.839, 93.840.
• This funding opportunity was created on 2019-09-03.
• Applicants must submit their applications by 2021-12-21. (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 $425,000.00 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.

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