Through our Notice of Special Interest (NOSI): Using Targeted Degradation of Protein and non-Protein Targets for the Development of Novel Anti-Infectives, NIAID seeks research projects to discover and develop compounds that promote targeted protein degradation of viral, bacterial, parasitic, or fungal pathogen components. Compounds targeting non-protein targets (e.g., RNA) are also welcome. The overarching aim is to target mechanisms integral for the replication, growth, survival, or virulence of a pathogen, as well as toxin or toxin-related targets.
To develop such novel anti-infectives, consider pursuing the following basic and translational research topics:
- Identify additional pathogen and host proteins or enzymes that can be exploited in the development of novel degraders.
- Generate, characterize, and optimize degraders that stimulate the degradation of a specific pathogen, toxin, or host target.
- Develop and optimize relevant assays that allow for the assessment of the functionality of the degraders to degrade infectious targets.
- Determine the substrate specificity and kinetics of degrader interactions with the pathogen or host target or to the degradative machinery components.
- Determine rate limiting steps and factors that lead to the formation of a productive degradative complex to assist rational design and synthesis of effective degraders.
- Discover and develop highly selective ligands with high affinity to pathogen targets and host machinery components using ligand discovery technologies and relevant animal models or assays.
- Improve drug-like properties of degraders (e.g., physicochemical properties, pharmacokinetic profiles, cell permeability, solubility, oral bioavailability) through structure-activity relationship studies to improve therapeutic benefit as demonstrated in a small animal model.
Conversely, for this NOSI, you should not propose:
- Approaches that utilize gene-editing or gene knock-out/knock-in level, e.g., CRISPR-Cas9, or gene knock-down, e.g., RNA interference.
- Technologies that use targeted protein inactivation, which require adding an aminoacidic signal sequence (tag) to the protein of interest.
- Methods that directly alter or target the genome or epigenome of the host including those due to unforeseen off-target effects.
Review the NOSI for additional details.
Application Guidance
You may submit an application through any of the following parent notices of funding opportunities (NOFOs):
- NIH Research Project Grant (Parent R01, Clinical Trial Not Allowed)
- NIH Exploratory/Developmental Research Grant Program (Parent R21, Clinical Trial Not Allowed)
- NIH Small Research Grant Program (Parent R03, Clinical Trial Not Allowed)
- PHS 2023-2 Omnibus Solicitation of the NIH for Small Business Technology Transfer Grant Applications (Parent STTR [R41/R42], Clinical Trial Not Allowed)
- PHS 2023-2 Omnibus Solicitation of the NIH, CDC, and FDA for Small Business Innovation Research Grant Applications (Parent SBIR [R43/R44], Clinical Trial Not Allowed)
Requirements such as budget restrictions, project period length, and application deadline are determined by the NOFO through which you choose to apply.
But, in any case, you must include “NOT-AI-23-076” in the Agency Routing Identifier field (box 4B) of the SF 424 R&R form.
The first available due date is January 5, 2024. The NOSI expires on July 17, 2026.
If you have any questions, contact NIAID’s Dr. Raymond Slay at slayrm@niaid.nih.gov or 301-325-8578.