OpportunityTitle: Adapting Immunotherapy and Gene Editing Based Strategies for Targeting HIV Reservoirs in the CNS: Potential Benefits and Risks (R01 Clinical Trial Optional)
AdditionalInformationOnEligibility: Other Eligible Applicants include the following:  Alaska Native and Native Hawaiian Serving Institutions; Asian American Native American Pacific Islander Serving Institutions (AANAPISISs); Eligible Agencies of the Federal Government; Faith-based or Community-based Organizations; Hispanic-serving Institutions; Historically Black Colleges and Universities (HBCUs); Indian/Native American Tribal Governments (Other than Federally Recognized); Non-domestic (non-U.S.) Entities (Foreign Organizations); Regional Organizations; Tribally Controlled Colleges and Universities (TCCUs) ; U.S. Territory or Possession.
Description: 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 genome are being researched. However, majority of immunotherapy-based and gene editing based HIV eradication strategies are focused on the periphery. The brain presents a unique challenge where access is difficult and innovative strategies are needed to overcome the blood brain barrier. It is also important to understand the potential CNS toxicity of immunotherapy-based and gene-editing based approaches currently being tested in clinical trials
GrantorContactEmailDescription: If you have any problems linking to this funding announcement, please contact the NIH OER Webmaster
GrantorContactText: NIH OER Webmaster&lt;br/&gt;grantsinfo@nih.gov