November 17, 2023

Recent advances and challenges of HIV therapeutics

Dr. Amber Khan and Dr. Nandagopal Paneerselvam in Prof. Brian Lawson's lab review challenges and successes of broadly neutralizing antibodies (bNAbs) and antiretroviral therapy for HIV treatment.

Antiretrovirals to CCR5 CRISPR/Cas9 gene editing - A paradigm shift chasing an HIV cure.

The evolution of drug-resistant viral strains and anatomical and cellular reservoirs of HIV pose significant clinical challenges to antiretroviral therapy. CCR5 is a coreceptor critical for HIV host cell fusion, and a homozygous 32-bp gene deletion (Δ32) leads to its loss of function. Interestingly, an allogeneic HSCT from an HIV-negative Δ32 donor to an HIV-1-infected recipient demonstrated a curative approach by rendering the recipient’s blood cells resistant to viral entry. Ex vivo gene editing tools, such as CRISPR/Cas9, hold tremendous promise in generating allogeneic HSC grafts that can potentially replace allogeneic Δ32 HSCTs. Here, we review antiretroviral therapeutic challenges, clinical successes, and failures of allogeneic and allogeneic Δ32 HSCTs, and newer exciting developments within CCR5 editing using CRISPR/Cas9 in the search to cure HIV.

https://www.sciencedirect.com/science/article/abs/pii/S1521661623005041

Access article here.

Broadly neutralizing antibodies targeting HIV: Progress and challenges. 

Anti-HIV broadly neutralizing antibodies (bNAbs) offer a novel approach to treating, preventing, or curing HIV. Pre-clinical models and clinical trials involving the passive transfer of bNAbs have demonstrated that they can control viremia and potentially serve as alternatives or complement antiretroviral therapy (ART). However, antibody decay, persistent latent reservoirs, and resistance impede bNAb treatment. This review discusses recent advancements and obstacles in applying bNAbs and proposes strategies to enhance their therapeutic potential. These strategies include multi-epitope targeting, antibody half-life extension, combining with current and newer antiretrovirals, and sustained antibody secretion. 

https://www.sciencedirect.com/science/article/abs/pii/S1521661623005727

Access article here.