Exploring the Roles of Biomolecular Condensates (BMCs) in HIV replication, latency, or pathogenesis in the context of substance use disorders (R21/R33 Clinical Trial Not Allowed) | RFA DA 21 004

Opportunity Information: Apply for RFA DA 21 004

This National Institutes of Health (NIH) funding opportunity, RFA-DA-21-004, supports research that investigates how biomolecular condensates (BMCs) and the molecules that regulate them influence HIV or SIV infection and disease, specifically in the context of substance use disorders. Biomolecular condensates are membrane-less cellular compartments formed by processes such as phase separation, and they can organize proteins and nucleic acids in ways that strongly shape gene expression, chromatin behavior, stress responses, and antiviral defense. The core goal of the announcement is to encourage studies that connect this emerging area of cell biology to key HIV questions that matter for prevention and treatment, while also accounting for the biological and clinical complications introduced by exposure to addictive substances.

The scientific scope is broad but clearly centered on HIV/SIV replication, persistence, and disease mechanisms where BMCs may play a direct or indirect role. Proposed projects can focus on how BMCs participate in HIV entry and early infection events, how they affect viral replication steps including viral gene expression, and how they may contribute to the establishment or maintenance of HIV latency. Latency-related work can include how condensates influence chromatin structure and transcriptional regulation around the provirus, which is directly relevant to why HIV persists despite effective antiretroviral therapy. The opportunity also highlights HIV pathogenesis, including neurodegenerative processes, signaling interest in how condensate biology might shape HIV-associated neurologic injury or other tissue-level disease outcomes.

Another emphasized area is the host side of the equation: applicants are invited to examine how BMCs or their regulators alter host cell functions in settings relevant to HIV infection and treatment. This includes the intersection of condensate behavior with antiretroviral therapy (ART), as well as how exposure to addictive substances could reprogram cellular pathways that then alter condensate formation, composition, or function. In practical terms, this could mean studying whether drugs of abuse change stress granules, nuclear bodies, transcriptional condensates, or other phase-separated assemblies that in turn affect viral transcription, immune signaling, inflammation, or neuronal health. The framing is designed to push beyond purely descriptive work and toward mechanistic understanding of how substance exposure may shift cellular organization in ways that promote HIV replication, help maintain latency, or worsen pathogenesis.

The mechanism is an R21/R33, which generally supports a staged approach where early, exploratory work (R21) can transition to a more advanced, developmental phase (R33) if predefined milestones are met. This structure fits projects where initial feasibility or proof-of-concept experiments are needed before scaling into deeper mechanistic studies. The notice specifies "Clinical Trial Not Allowed," meaning the funded research cannot include clinical trial activities; it is intended for non-trial research such as basic, translational, or preclinical studies, and other human or animal research that does not meet the definition of a clinical trial.

From an administrative standpoint, this is a discretionary NIH grant opportunity in the health and education activity category, associated with CFDA 93.279. The opportunity was created on 2020-02-24, with an original closing date of 2020-07-20. The source listing does not provide an award ceiling or the expected number of awards, so applicants would typically refer to the full announcement and NIH budget guidance for typical costs and project period expectations under the R21/R33 structure.

Eligibility is intentionally expansive to encourage participation from a wide range of institutions and organizations. Eligible applicants include state, county, and local governments; 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; tribal organizations that are not federally recognized; public housing authorities/Indian housing authorities; nonprofits with or without 501(c)(3) status (other than institutions of higher education); for-profit organizations (other than small businesses); and small businesses. The announcement also calls out additional eligible applicant categories, 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, non-U.S. (foreign) entities, and U.S. territories or possessions. This broad eligibility reflects a desire to draw on diverse scientific perspectives and community-relevant expertise in both HIV and substance use research.

Overall, the opportunity is aimed at building a clearer, mechanistic picture of how condensate biology intersects with HIV replication and persistence, and how substance use-related exposures may modify these cellular systems in ways that influence outcomes. The expected impact is to open new lines of investigation and potentially identify novel targets or strategies relevant to HIV cure efforts (through latency and gene regulation studies), improved control of viral replication, and mitigation of HIV-related pathogenesis, particularly in populations and contexts affected by substance use disorders.

• The National Institutes of Health in the education, health sector is offering a public funding opportunity titled "Exploring the Roles of Biomolecular Condensates (BMCs) in HIV replication, latency, or pathogenesis in the context of substance use disorders (R21/R33 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): 93.279.
• This funding opportunity was created on 2020-02-24.
• Applicants must submit their applications by 2020-07-20. (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.

Apply for RFA DA 21 004

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