Adapting Immunotherapy and Gene Editing Based Strategies for Targeting HIV Reservoirs in the CNS: Potential Benefits and Risks (R21 Clinical Trial Optional)

Funding Opportunity RFA-MH-21-226 from the NIH Guide for Grants and Contracts. Companion to R01 (RFA-MH-21-225). The shock and kill strategy is one of the commonly used approaches for targeting latent reservoirs in hopes to cure HIV-1. It is based on the concept of purposely inducing reactivation of latent reservoirs in ART (antiretroviral therapy)-treated individuals by using stimulatory agents. However, it has become increasingly evident that attempts at elimination of HIV-1 reservoirs through latency reactivating agents (LRA) -mediated reactivation alone may not be sufficient. Novel strategies such as immunotherapy and gene excision therapies to optimize the recognition and elimination of reservoir cells such are being conceptualized and researched. Immunotherapy strategies like therapeutic vaccines to enhance HIV-1-specific CTL (cytotoxic T-cell) response, Chimeric Antigen Receptor T-cells (CAR-T cells) therapies, broadly neutralizing antibodies, dual-affinity retargeting antibodies that not only bind to HIV-1 viral envelope antigen but also activate the CTL response, and immune modulators, such as anti-PD1 (programmed cell death protein-1) or anti-CTL4 antibodies, to correct the immune exhaustion noticed in ART-treated individuals are being developed. In addition to immunotherapy strategies, Recombinant TALEN or CRISPR/Cas9 gene editing molecules delivered to latently infected cells designed to induce cleavage at highly conserved regions of the integrated HIV provirus...
Source: NIH Funding Opportunities (Notices, PA, RFA) - Category: Research Source Type: funding