抗体
抗原
生物
重编程
免疫球蛋白轻链
B细胞
免疫球蛋白重链
分子生物学
细胞生物学
细胞
免疫学
遗传学
作者
Paula M. Cannon,Geoffrey L. Rogers,Chun Huang,Atishay Mathur,Xiaoli Huang,Hsu-Yu Chen,Kalya Stanten,Heidy Morales,Chan-Hua Chang,Eric J. Kezirian
出处
期刊:Research Square - Research Square
日期:2023-07-17
被引量:1
标识
DOI:10.21203/rs.3.rs-3117686/v1
摘要
We describe a genome editing strategy to reprogram the immunoglobulin heavy chain (IgH) locus of human B cells to express custom molecules that respond to immunization. These heavy chain antibodies (HCAbs) comprise a custom antigen-recognition domain linked to an Fc domain derived from the IgH locus and can be differentially spliced to express either B cell receptor (BCR) or secreted antibody isoforms. The HCAb editing platform is highly flexible, supporting antigen-binding domains based on both antibody and non-antibody components, and also allowing alterations in the Fc domain. Using HIV Env protein as a model antigen, we show that B cells edited to express anti-Env HCAbs support the regulated expression of both BCRs and antibodies, and respond to Env antigen in a tonsil organoid model of immunization. In this way, human B cells can be reprogrammed to produce customized therapeutic molecules with the potential for
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