Article
Non-viral precision T cell receptor replacement for personalized cell therapy.
Nature - 1 Mar 2023
Foy Susan P, Jacoby Kyle, Bota Daniela A, Hunter Theresa, Pan Zheng, Stawiski Eric, Ma Yan, Lu William, Peng Songming, Wang Clifford L, Yuen Benjamin, Dalmas Olivier, Heeringa Katharine, Sennino Barbara, Conroy Andy, Bethune Michael T, Mende Ines, White William, Kukreja Monica, Gunturu Swetha, Humphrey Emily, Hussaini Adeel, An Duo, Litterman Adam J, Quach Boi Bryant, Ng Alphonsus H C, Lu Yue, Smith Chad, Campbell Katie M, Anaya Daniel, Skrdlant Lindsey, Huang Eva Yi-Hsuan, Mendoza Ventura, Mathur Jyoti, Dengler Luke, Purandare Bhamini, Moot Robert, Yi Michael C, Funke Roel, Sibley Alison, Stallings-Schmitt Todd, Oh David Y, Chmielowski Bartosz, Abedi Mehrdad, Yuan Yuan, Sosman Jeffrey A, Lee Sylvia M, Schoenfeld Adam J, Baltimore David, Heath James R, Franzusoff Alex, Ribas Antoni, Rao Arati V, Mandl Stefanie J
Abstract excerpt
T cell receptors (TCRs) enable T cells to specifically recognize mutations in cancer cells1-3. Here we developed a clinical-grade approach based on CRISPR-Cas9 non-viral precision genome-editing to simultaneously knockout the two endogenous TCR genes TRAC (which encodes TCRα) and TRBC (which encodes TCRβ). We also inserted into the TRAC locus two chains of a neoantigen-specific TCR (neoTCR) isolated from...
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