Heavy-chain immunoglobulin locus editing in rhesus macaque B cells to confer antibody production

Antibody-based immunotherapies are promising; however, their application remains limited to acute diseases due to rapid clearance of antibodies <i>in vivo</i>. Some chronic conditions could benefit from sustained therapeutic antibody expression. One such instance is human immunodeficiency virus type 1 (HIV-1), where the efficiency of broadly neutralizing antibodies by passive immunization has been limited in clinical trials. B cell editing to enable sustained production of an antibody of interest <i>in vivo</i> could address this issue. However, the long-term potential of this approach and feasibility to perform editing in B cells from people living with HIV remain to be determined. We investigated editing of rhesus macaque B cells from healthy or simian/human immunodeficiency virus (SHIV)-infected animals to model this approach. An antibody-encoding cassette was inserted in the immunoglobulin locus by CRIPSR-Cas9-mediated <i>ex vivo</i> B cell editing. Similar indel efficiencies were achieved in B cells from both uninfected and infected animals, and expression of the antibody of interest was detected in up to 10% of uninfected B cells. This study paves the way for future <i>in vivo</i> work to assess the long-term potential of this approach and its impact on B cell development and function in an immunocompetent <i>in vivo</i> nonhuman primate model of HIV persistence and cure.