Antibody-based immunotherapies are promising; however, their application remains limited to acute diseases due to rapid clearance of antibodies. 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 interestcould 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-mediatedB 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 futurework to assess the long-term potential of this approach and its impact on B cell development and function in an immunocompetentnonhuman primate model of HIV persistence and cure. in vivo in vivo ex vivo in vivo in vivo
