CRISPR–Cas12a was used to directly replace mouse antibody variable chain genes with human versions in primary B cells. The edited cells underwent affinity maturation in vivo, improving the potency of HIV-1 and SARS-CoV-2 neutralizing antibodies without loss of bioavailability. Affinity maturation of edited cells also enables new vaccine models and adaptive B cell therapies.
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References
Rogers, G. L. & Cannon, P. M. Genome edited B cells: a new frontier in immune cell therapies. Molecul. Therapy 29, 3192–3204 (2021). A review article that describes B cell editing approaches and their applications.
Hartweger, H. et al. HIV-specific humoral immune responses by CRISPR/Cas9-edited B cells. J. Exp. Med. 216, 1301–1310 (2019). One example of an intron-editing approach that introduced antibody heavy and light chains into the immunoglobulin heavy chain (IgH) intron locus.
Yin, Y. et al. In vitro affinity maturation of broader and more-potent variants of the HIV-1-neutralizing antibody CAP256-VRC26.25. Proc. Natl Acad. Sci. USA 118, e2106203118 (2021). Applied CRISPR editing to create a library of antibody variants in a B cell line for subsequent selection.
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Voss, J. E. et al. Reprogramming the antigen specificity of B cells using genome-editing technologies. eLife 8, e42995 (2019). A pioneering paper in B cell engineering techniques that introduced a heavy-chain gene into human B cells with two CRISPR–Cas9 cuts.
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This is a summary of: Yin, Y. et al. In vivo affinity maturation of mouse B cells reprogrammed to express human antibodies. Nat. Biomed. Eng. https://doi.org/10.1038/s41551-024-01179-6 (2024).
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Affinity maturation of CRISPR-engineered B cell receptors in vivo. Nat. Biomed. Eng (2024). https://doi.org/10.1038/s41551-024-01184-9
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DOI: https://doi.org/10.1038/s41551-024-01184-9
