National Heart, Lung, and Blood Institute 5P01HL183483-02

B cells as boostable factories for HIV inhibition

This NIH-funded project focuses on engineering B cells using CRISPR/Cas9 to produce anti-HIV antibodies in vivo, aiming to develop a novel cell therapy for HIV cure through gene editing and immunotherapy approaches.

Description

We are developing reprogrammed B cells to secret anti-HIV molecules. We use CRISPR/Cas9 genome editing to precisely insert custom antibody cassettes at the endogenous immunoglobulin locus. The engineered B cells maintain the ability to respond to HIV Env protein and can differentiate into plasma cells and memory phenotypes. This approach aims to create in vivo biofactories for long-term secretion of anti-HIV antibodies, concentrated in lymphoid tissues. The project extends to in vivo gene editing of B cells or HSC precursors using re-targeted lentiviral-like particles and helper-dependent adenovirus vectors, evaluated in humanized mouse models and NHP studies. The goal is to demonstrate that reprogrammed B cells can be created in vivo, respond to HIV vaccination and replication, and secrete antibodies to control HIV, contributing to a potential in vivo cell therapy for HIV cure.

View original record