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    • 2. 发明申请
    • TARGETED DISRUPTION OF THE T CELL RECEPTOR
    • 靶向破坏T细胞受体
    • WO2017106528A3
    • 2017-07-27
    • PCT/US2016066975
    • 2016-12-15
    • SANGAMO BIOSCIENCES INC
    • LEE GARY KPASCHON DAVIDZHANG LEI
    • A61K35/15A61K35/17A61K35/545C07K14/705C12N5/0783C12N5/0789C12N5/10C12N9/22C12N15/62
    • C12N15/52C12N5/0603C12N5/0606C12N5/0636C12N5/0696C12N9/16C12N15/62
    • Disclosed herein are methods and compositions for inactivating TCR genes, using engineered nucleases comprising at least one DNA binding domain and a cleavage domain or cleavage half-domain in conditions able to preserve cell viability. Polynucleotides encoding nucleases, vectors comprising polynucleotides encoding nucleases and cells comprising polynucleotides encoding nucleases and/or cells comprising nucleases are also provided. Disclosed herein are also methods and compositions for expressing a functional exogenous TCR in the absence of endogenous TCR expression in T lymphocytes, including lymphocytes with a central memory phenotype. Polynucleotides encoding exogenous TCR, vectors comprising polynucleotides encoding exogenous TCR and cells comprising polynucleotides encoding exogenous TCR and/or cells comprising exogenous TCR are also provided.
    • 本文公开了使用在能够保存细胞活力的条件下包含至少一个DNA结合结构域和切割结构域或切割半结构域的工程化核酸酶来灭活TCR基因的方法和组合物。 还提供了编码核酸酶的多核苷酸,包含编码核酸酶的多核苷酸的载体和包含编码核酸酶的多核苷酸和/或包含核酸酶的细胞的细胞。 本文还公开了用于在T淋巴细胞(包括具有中枢记忆表型的淋巴细胞)中不存在内源性TCR表达的情况下表达功能性外源性TCR的方法和组合物。 还提供了编码外源TCR的多核苷酸,包含编码外源TCR的多核苷酸的载体和包含编码外源TCR的多核苷酸和/或包含外源TCR的细胞的细胞。