Understanding Phage Biology to Support the Development of Bacteriophage Therapy (R21 Clinical Trial Not Allowed) | RFA AI 19 065

Opportunity Information: Apply for RFA AI 19 065

The National Institutes of Health (NIH) funding opportunity titled "Understanding Phage Biology to Support the Development of Bacteriophage Therapy (R21 Clinical Trial Not Allowed)" (Funding Opportunity Number RFA-AI-19-065; CFDA 93.855) supports early-stage, exploratory research aimed at closing key scientific and regulatory knowledge gaps that slow down the development of bacteriophages as tools to prevent and treat drug-resistant bacterial infections. The focus is on basic and translational work that improves foundational understanding of phage biology and how phages interact with bacteria and hosts, with the practical goal of making bacteriophage-based therapeutics easier to develop, evaluate, and regulate. Because the mechanism is an R21, the intent is typically to encourage high-impact, innovative projects that generate strong preliminary evidence or new concepts rather than large, definitive programs. Clinical trials are not allowed under this announcement, meaning applications should avoid proposing prospective studies in humans that test safety and/or efficacy outcomes.

This opportunity sits in the broader public health context of antimicrobial resistance, where conventional antibiotics are losing effectiveness and alternative or complementary approaches are urgently needed. Bacteriophage therapy has long been viewed as promising because phages can be highly specific to bacterial targets and can evolve alongside bacterial resistance mechanisms. At the same time, the same properties that make phages biologically powerful can complicate consistent manufacturing, characterization, dosing strategies, and regulatory assessment. NIH is using this initiative to stimulate research that makes phage therapy more predictable and standardized by improving scientific understanding in areas that regulators and developers need in order to assess product quality, safety, and likely performance.

Projects responsive to the initiative would generally be those that clarify how phages work at a mechanistic level and how that mechanistic understanding can translate into better therapeutic design and evaluation frameworks. This can include studying determinants of host range and specificity, adsorption and entry processes, replication dynamics, burst size, latency and lysis decisions, and how environmental conditions influence phage activity. It can also include research on bacterial resistance to phages and strategies to manage or anticipate that resistance, such as understanding receptor mutations, CRISPR and other bacterial defense systems, and the evolutionary tradeoffs that occur when bacteria adapt to evade phage predation. Another major theme consistent with the goals of the announcement is improving the ability to measure and predict phage behavior in complex biological settings, including biofilms or polymicrobial environments, and clarifying the implications of phage-bacteria interactions for treatment durability.

On the translational side, the initiative is oriented toward generating knowledge that supports product development and regulation, which often hinges on questions like how to define and measure potency, how to characterize complex phage preparations, how to ensure consistency across manufacturing lots, and how to understand factors that affect stability and activity during storage and delivery. Applications could also address how to assess potential safety concerns using non-clinical approaches, such as understanding immune recognition of phage components, inflammatory consequences of rapid bacterial lysis, or the risk profile of different phage types based on genomic features. While the announcement does not permit clinical trials, it still encourages work that moves the field closer to clinical translation by producing the kinds of standardized data, assays, and biological insights that ultimately enable rigorous preclinical packages and clear regulatory pathways.

Eligibility for this discretionary grant is broad and includes many categories of organizations that commonly apply to NIH research programs. Eligible applicants include state, county, city or township, and special district governments; independent school districts; public and state-controlled institutions of higher education; private institutions of higher education; federally recognized Native American tribal governments; Native American tribal organizations other than federally recognized tribal governments; public housing authorities and Indian housing authorities; nonprofit organizations with and without 501(c)(3) status (excluding institutions of higher education when relevant to those categories); for-profit organizations other than small businesses; and small businesses. The announcement also explicitly highlights additional eligible applicant types, including 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, U.S. territories or possessions, Indian/Native American Tribal Governments other than federally recognized entities, and non-U.S. organizations (foreign entities). This wide eligibility signals an interest in drawing ideas and capabilities from many settings, including institutions with specialized community, regional, or international expertise relevant to resistant infections and phage research.

Administratively, the opportunity is a grant (Funding Instrument Type: Grant) in the health domain (Funding Activity Category: Health) and was created on October 10, 2019, with an original closing date of March 18, 2020. The public information provided does not specify an award ceiling or expected number of awards, which typically means applicants would need to consult the full NIH funding announcement and associated institute guidance for budget limits, project period expectations, and review criteria. Overall, the core message of the opportunity is to build the scientific base needed to make bacteriophage therapy more reliable and easier to evaluate, with research that is innovative, foundational, and directly relevant to eventual therapeutic development, while stopping short of human clinical testing.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "Understanding Phage Biology to Support the Development of Bacteriophage Therapy (R21 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): 93.855.
• This funding opportunity was created on 2019-10-10.
• Applicants must submit their applications by 2020-03-18. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
• 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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