Extracellular RNA carrier subclasses in processes relevant to Substance Use Disorders or HIV infection (R21- Clinical Trial Not Allowed) | PAR 20 148

Frequently Asked Questions (FAQs)

What is the funding opportunity described here?

This is a National Institutes of Health (NIH) funding opportunity announcement (FOA) PAR-20-148. It invites applications for exploratory, early-stage research using the NIH R21 mechanism focused on extracellular RNA (exRNA) carriers and how specific carrier subclasses influence biological processes tied to substance use disorders (SUDs) and/or HIV infection, especially in the central nervous system (CNS).

What activity code or grant mechanism is used?

The FOA uses the NIH R21 mechanism, which is intended for exploratory and early-stage, proof-of-concept work that can open up new directions rather than support a fully mature, long-term research program.

What is the scientific focus of this FOA?

The scientific emphasis is on understanding how extracellular RNAs, which circulate outside cells and are packaged or transported in distinct carrier types, may contribute to HIV infection, viral latency, or disease pathogenesis in the CNS, as well as mechanisms relevant to substance use disorders.

What are "exRNA carriers" in the context of this opportunity?

In this FOA, exRNA carriers refer to the distinct types of extracellular particles or structures that package or transport RNA outside cells. The announcement specifically notes extracellular vesicles and other exRNA-containing particles, and it is interested in how different carrier subclasses may have different biological effects.

What kinds of research approaches are encouraged?

The FOA describes two broad approaches: (1) biological or mechanistic studies that clarify how specific exRNA carrier subclasses mediate processes relevant to HIV and/or SUDs (for example, signaling, immune modulation, neuroinflammation, neuronal injury, HIV persistence, and neuropathogenesis), and (2) technology and tool development to improve how exRNA carriers are isolated, classified, quantified, and characterized, including how their RNA cargo and functional effects are analyzed.

Does the FOA prioritize CNS-related outcomes?

Yes. The announcement highlights CNS-relevant pathways and encourages work that connects exRNA carrier subclasses to HIV-related CNS pathogenesis, viral latency and persistence, and SUD-related changes in brain function.

Is HIV required to be part of the proposed research?

The FOA is focused on biological processes tied to substance use disorders and/or HIV infection. Based on the description provided, applicants can align their project with HIV, SUDs, or the intersection of both, as long as the research centers on exRNA carriers and their roles in relevant mechanisms.

Are projects about substance use disorders (SUDs) within scope even without HIV?

Yes. The FOA explicitly includes biological processes tied to SUDs and/or HIV infection, and it emphasizes mechanisms relevant to SUDs as part of the core scientific interest.

What is meant by "Clinical Trial Not Allowed" for this FOA?

The FOA is explicitly labeled "Clinical Trial Not Allowed," meaning the proposed work must be non-clinical-trial research. Examples mentioned include mechanistic studies, method development, or preclinical investigations, rather than testing interventions in human participants as clinical trials.

Can applicants include human participants in any way?

The information provided only states that clinical trials are not allowed and gives examples of acceptable non-clinical-trial work (mechanistic, method development, preclinical). Whether any specific human-participant research designs are allowable is not spelled out in the provided text; applicants would need to ensure their project does not meet the NIH definition of a clinical trial for this FOA.

What types of technology development are considered responsive?

The FOA highlights improved methods and tools to isolate, classify, quantify, and characterize extracellular vesicles or other exRNA carriers, and to better analyze their RNA cargo and functional effects. Examples given include innovations in separation methods, analytics, imaging, single-particle profiling, RNA sequencing approaches tailored to low-input exRNA, and assays that connect carrier subclass to functional outcomes.

Is assay development or method development appropriate under this FOA?

Yes. Method and tool development is explicitly included as one of the two broad encouraged approaches, particularly where it enables more precise study of exRNA carrier subclasses and their functional roles.

What is the maximum award amount mentioned?

The opportunity is described as having an award ceiling of $200,000, consistent with the R21 intent to support high-impact, early proof-of-concept projects.

Is this a discretionary grant program?

Yes. The opportunity is described as being offered as a discretionary grant program within the NIH health mission space.

What CFDA number is associated with this opportunity?

The description lists CFDA 93.279.

When was the FOA created, and what closing date is listed?

The FOA is described as having been created on 2020-03-25, with an original closing date listed as 2023-05-07.

Is the FOA still active?

The description notes that applicants would need to verify current submission dates and whether the announcement remains active through NIH systems and the funding announcement page. The provided information alone does not confirm current active status.

Who is eligible to apply?

Eligibility is broad. The listed eligible applicants include: state, county, city, and special district governments; independent school districts; public and state-controlled colleges and universities; private institutions of higher education; federally recognized Native American tribal governments; tribal organizations (including those other than federally recognized tribal governments); public housing authorities/Indian housing authorities; nonprofits with or without 501(c)(3) status (excluding higher education institutions in those nonprofit categories); for-profit organizations other than small businesses; and small businesses.

Are minority-serving institutions specifically called out as eligible?

Yes. The FOA highlights additional eligible applicant categories including Historically Black Colleges and Universities (HBCUs), Hispanic-serving Institutions, Tribally Controlled Colleges and Universities (TCCUs), Alaska Native and Native Hawaiian Serving Institutions, and Asian American Native American Pacific Islander Serving Institutions (AANAPISIs).

Are faith-based or community-based organizations eligible?

Yes. The FOA explicitly includes faith-based or community-based organizations among eligible applicants.

Can federal agencies apply?

Yes. Eligible applicant categories include federal agencies.

Are U.S. territories or possessions eligible?

Yes. The FOA includes U.S. territories or possessions as eligible, and also lists regional organizations.

Are non-U.S. (foreign) entities eligible to apply?

Yes. The description explicitly notes that non-U.S. (foreign) entities are included as eligible applicants, indicating openness to strong science conducted outside the U.S., subject to NIH policies and FOA requirements.

What is the main goal of the research supported by this FOA?

The core goal is to stimulate research that disentangles the roles of different exRNA carrier subclasses in CNS-relevant pathways impacted by HIV and/or substance use. The FOA aims to accelerate progress in understanding exRNA-mediated intercellular communication in disease mechanisms and to support the tools needed to study these carriers more precisely.

What kinds of biological processes are mentioned as relevant to proposed studies?

The FOA mentions processes such as signaling, immune modulation, neuroinflammation, neuronal injury, and other mechanisms that may shape HIV persistence and neuropathogenesis or contribute to SUD-related changes in brain function.

How does this FOA connect exRNA biology to HIV outcomes?

It emphasizes understanding how exRNAs and their carrier subclasses may contribute to HIV infection, viral latency, and disease pathogenesis in the CNS, including factors that may influence persistence or neuropathogenesis.

How does this FOA connect exRNA biology to substance use disorders?

It encourages studies of mechanisms relevant to SUDs, including how substance use may intersect with extracellular communication networks and contribute to changes in brain function through exRNA carrier-mediated pathways.

Is biomarker development a stated focus?

The description does not explicitly state biomarker development as a primary focus, but it notes that tool-building can help translate exRNA biology into clearer mechanisms, biomarkers, or future therapeutic strategies. Any biomarker-oriented work would need to remain aligned with the stated emphasis on carrier subclasses, mechanisms, and/or enabling technologies, and must not be a clinical trial.

Does the FOA support therapeutic intervention testing?

The FOA is labeled "Clinical Trial Not Allowed" and frames the work as mechanistic, method development, or preclinical rather than testing interventions in human participants as clinical trials. The provided information does not describe support for clinical testing of therapies.

What is the general rationale for offering this FOA now?

The announcement is positioned as addressing a relatively young but rapidly evolving area: how exRNA and diverse extracellular carrier types participate in intercellular communication and disease mechanisms. It targets HIV- and SUD-related CNS outcomes while also encouraging technological advances that remove bottlenecks in studying exRNA carriers.