We have developed a method to introduce novel paratopes into the human antibody
repertoire by modifying the immunoglobulin (Ig) genes of mature B cells directly using
genome editing technologies. We used CRISPR-Cas9 in a homology directed repair
strategy, to replace the heavy chain (HC) variable region in B cell lines with that from an HIV
broadly neutralizing antibody (bnAb), PG9. Our strategy is designed to function in cells that
have undergone VDJ recombination using any combination of variable (V), diversity (D) and …

HIV infection is a global health concern affecting roughly 37 million people and still no
effective vaccine is available for prevention. While rare, HIV broadly neutralizing antibodies
(bnAbs) have been isolated from patients. These antibodies have been shown to be
protective in animal models if present at the time of challenge in passive transfer
experiments. Thus, elicitation of HIV bnAbs is a central goal for vaccine design. These
antibodies, however, contain rare features not present in the naïve human antibody …