Advanced therapeutic modalities like gene therapy and gene editing are increasingly being explored for HIV treatment, with several companies and institutions making notable strides.
CRISPR-Based Therapy Shows Safety and Temporary Viral Suppression
Excision BioTherapeutics' EBT-101, a CRISPR-based gene editing therapy, has shown promising initial results in a phase 1/2 trial (NCT05144386). The trial met its primary safety endpoint and secondary biodistribution/immunogenicity endpoint. Data presented at the American Society of Gene & Cell Therapy (ASGCT) 27th Annual Meeting indicated that the therapy was safely delivered, targeting HIV DNA reservoirs in human cells.
Principal investigator Rachel M. Presti, MD, PhD, Professor of Medicine, Washington University School of Medicine, St. Louis, stated, "Initial data from the EBT-101-001 trial provides important clinical evidence that a gene editing treatment modality can be safely delivered for targeting the HIV DNA reservoirs in human cells."
The trial reported no serious adverse events (AEs) related to the therapy. Among the five participants who received a single infusion of EBT-101, three temporarily stopped antiretroviral therapy but experienced viral rebound and had to restart treatment. Notably, one participant maintained viral suppression for 16 weeks post-treatment discontinuation.
Novel Gene Editing Approaches
At the ASGCT meeting, various novel gene editing approaches were discussed, including integrase-mediated programmable genomic integration, base editing for neurological disorders, and DNA polymerase editors. Janice Chen, PhD, cofounder and chief technology officer of Mammoth Biosciences, highlighted a clinical trial evaluating a multiplex CRISPR/Cas9 system for treating latent HIV.
Gene Therapy Targeting HIV-Specific Genes
AGT103-T, a gene therapy developed by American Gene Technologies and now under Addimmune, uses miRNA to block two HIV-specific genes: the CCR5 receptor and the regulatory TAT protein. The TAT protein facilitates the transcription of viral RNA into mRNA in the host cell.
Marcus Conant, MD, chief medical officer, Addimmune, discussed results from an early phase 1 trial (NCT04561258) involving seven patients, noting promising efficacy signals. This approach aims to suppress HIV by directly targeting viral components within the host cell.
