Explore New Technologies To Deliver In Vivo Gene Therapeutics for HIV Cure

Gene therapy has the potential to cure numerous diseases and conditions, including HIV. However, current strategies focusing primarily on ex vivo genetically modified cells remain relatively inefficient and technically complex processes. Using in vivo gene therapy strategies instead will be minimally invasive, less toxic, and possibly increase accessibility and application of anti-HIV gene therapeutics.

NIAID seeks applications proposing research developing and evaluating novel targeting technologies to deliver anti-HIV gene therapies to specific cells in vivo through the funding opportunity announcement (FOA) New Technologies for the In Vivo Delivery of Gene Therapeutics for an HIV Cure (R01, Clinical Trial Not Allowed).

Research Objectives and Scope

This FOA will support projects to develop and evaluate novel targeting technologies to deliver anti-HIV gene therapies to specific cells or sites in vivo. The overarching goal is to fill the knowledge gap in efficiently delivering gene therapeutics to reservoir sites or specific cell subsets in vivo.

Applicants should have a therapeutic approach that has shown some anti-HIV efficacy, with supporting data at the time of submission. Ideal projects should focus on developing and optimizing delivery vehicles or cell-targeting strategies, combined with an existing therapeutic strategy, for targeted therapeutic delivery following in vivo administration in animal models.

This FOA will support targeted in vivo delivery of a broad range of gene and cell therapeutic approaches including but not limited to:

• Genome or epigenome editing strategies that directly target HIV proviral DNA in actively- or latently-infected cells
• In vivo application of inhibitory modalities currently used to generate ex-vivo-modified HIV-resistant cells
• Direct in vivo generation of cells with new or improved immune properties to target and eliminate HIV-infected cells
• Vectored immunotherapy for effective in vivo antibody production

This FOA also supports a broad range of delivery platforms, including viral vectors, non-viral methods of gene delivery such as polymer or liposome-based nanoparticles, and nucleic acid complexes modified to facilitate uptake and delivery into cells and exosomes.

Responsive Areas of Research Interest

Examples of research activities NIAID will support through this initiative include:

• Developing and evaluating novel delivery techniques for gene editing enzymes and other gene therapeutic strategies
• Directed evolution strategies to identify novel vectors with enhanced cell specificity
• Optimizing in vivo gene transfer by enhancing delivery of the therapeutic modality to the nucleus (e.g., increasing efficiency of nuclear transport and uptake of genetic payloads)
• Strategies for temporal and quantitative control of transgene expression to regulate timing, level, and cell-specificity of transgene expression in vivo
• Strategies to reduce or mitigate immune responses that impact efficacy, such as immunogenicity of delivery vectors or transgenes and pre-existing immunity to delivery vectors

Find a longer list of examples in the FOA itself. 

Nonresponsive Areas of Research Interest

If you propose the following research, NIAID will consider your application nonresponsive and will not review it.

• Discovering new gene therapeutic payloads (applicants should select a gene therapy strategy that has shown some anti-HIV efficacy, with supporting data, at the time of submission)
• Studies focused exclusively on ex vivo approaches for genetic modification
• Clinical trials

Deadline and Contact Information

Through this initiative, NIAID and the National Institute of Mental Health plan to fund four to six awards. The maximum project period is five years and application budgets are not limited but should reflect the actual needs of the proposed project.

This initiative has an annual due date. The submission deadline is 5 p.m. local time of the applicant organization on March 17, 2021; March 17, 2022; and March 17, 2023.

If you have NIAID-related questions about this FOA, contact Dr. Betty Poon, NIAID’s scientific/research contact.