Exavir Therapeutics Announces Preclinical Data Demonstrating Complete Elimination of HIV From Human Cells With LNP-Delivered Tat-Targeted CRISPR-Cas9

Exavir Therapeutics recently announced the publication of preclinical data for XVIR-TAT, Exavir’s proprietary gene editing program in early preclinical development as a potential cure for HIV. The research findings were published today in EBioMedicine in an article titled CRISPR-Cas9 Mediated Exonic Disruption for HIV-1 Elimination, and detailed in vitro data for an LNP-delivered, mRNA encoded, pro-viral DNA excision therapy based on CRISPR-Cas9 and computationally derived gRNAs targeting the HIV tat gene.

“In addition to our best-in-class ultra-long-acting INSTI small molecules, currently in IND-enabling studies, we are pursuing the holy grail of HIV research – a definitive cure. Our latest candidates build upon our previous work with collaborators on AAV-delivered CRISPR-Cas9 targeting the LTR and gag sequences. With next-generation LNP formulations and improved guide RNAs, we can safely and efficiently deliver powerful gene editing cargo to cells that are infected by HIV,” said Howard Gendelman, scientific co-founder of Exavir Therapeutics and Professor in the Department of Pharmacology at the University of Nebraska Medical Center. “Our system is demonstrating near complete HIV elimination in vitro across several assays, with no detectable off target edits.”

As discussed in the publication, a library of guide RNAs (gRNAs) was developed using computational screening of over 4000 human clinical HIV samples. Selected TatDE multiplex gRNAs demonstrated anti-retroviral activity and near complete suppression of virus across various assays, including co-transfection challenge of un-infected cells, as well as ribonucleoprotein electroporation, lentiviral delivery, and LNP-encapsulated mRNA-encoded delivery to infected cells.

In particular, LNP mRNA TatDE candidates demonstrated efficient delivery, nuclear localization, and up to 100% suppression of virus. These findings support the potential of LNP-based pro-viral DNA excision as an anti-retroviral therapy with the potential to completely eradicate HIV.

Key opinion leaders offered their praise. “Howard Gendelman and his colleagues at the University of Nebraska Medical Center have been doing forefront research on future HIV therapy. I know of no more rational and no better approach than he and his team have advanced,” said Dr. Robert C. Gallo, the Homer & Martha Gudelsky Distinguished Professor in Medicine, co-founder & director, Institute of Human Virology at the University of Maryland School of Medicine; co-founder & international scientific director, Global Virus Network.

HIV is one of the most deadly viral infections. It is estimated that there are nearly 1.2 million people in the United States living with HIV today, and over $30B is spent annually on antiretroviral HIV therapies worldwide.

XVIR-TAT is a CRISPR-nuclease based antiretroviral program in early preclinical development as a potential HIV cure. Exavir is currently optimizing LNP formulations for specific tropism to tissues of interest and advancing multiple genetic editing systems towards candidate selection, including Cas9-based TatDE excision.

Exavir Therapeutics is a preclinical stage biotechnology company dedicated to eliminating HIV and other viral infections with a broad modality-agnostic approach, beginning with long-acting antiviral therapeutics.