Publications by authors named "M Y Alpert"
eCD4-immunoglobulin (Ig) is an HIV entry inhibitor that mimics the engagement of both CD4 and CCR5 with the HIV envelope (Env) protein, a property that imbues it with remarkable potency and breadth. However, env is exceptionally genetically malleable and can evolve to escape a wide variety of entry inhibitors. Here we document the evolution of partial eCD4-Ig resistance in SHIV-AD8-infected rhesus macaques (RMs) treated with adeno-associated virus vectors encoding eCD4-Ig.
View Article and Find Full Text PDFHuman proteins repurposed as biologics for clinical use have been engineered through in vitro techniques that improve the affinity of the biologics for their ligands. However, the techniques do not select against properties, such as protease sensitivity or self-reactivity, that impair the biologics' clinical efficacy. Here we show that the B-cell receptors of primary murine B cells can be engineered to affinity mature in vivo the human CD4 domains of the HIV-1-entry inhibitor CD4 immunoadhesin (CD4-Ig).
View Article and Find Full Text PDFResults from multiple recent studies support further evaluation of 3,4-methylenedioxymethamphetamine (MDMA) in conjunction with psychotherapy (i.e., MDMA-Assisted Therapy) in the treatment of post-traumatic stress disorder (PTSD).
View Article and Find Full Text PDFArticle Synopsis
- - The study focuses on engineering a human protein biologic, specifically a half-life enhanced HIV-1 entry inhibitor, into murine B cells without compromising their natural ability to improve binding affinity over time.
- - By introducing CD4 domains into the heavy-chain loci of these B cells and transferring them into wild-type mice, the modified cells successfully proliferated and produced antibodies that neutralize HIV-1 more effectively.
- - The findings suggest that affinity maturation techniques can enhance the therapeutic potential of non-antibody protein biologics, improving their effectiveness without losing important pharmacokinetic qualities.
Article Synopsis
- Researchers are engineering human proteins for clinical use but face challenges like sensitivity to proteases and self-reactivity, which can limit effectiveness.
- The study specifically enhances B-cell receptors in mice to express a modified HIV-1 entry inhibitor, allowing B cells to mature and produce antibodies that can bind more effectively to HIV-1.
- This approach resulted in a more than ten-fold increase in the ability of the modified protein to neutralize various HIV-1 strains, paving the way for better therapeutic development without losing desirable drug properties.