TARGETED DISRUPTION OF T CELL RECEPTOR GENES USING ENGINEERED ZINC FINGER PROTEIN NUCLEASES

摘要

Disclosed herein are methods and compositions for inactivating TCR genes, using zinc finger nucleases (ZFNs) comprising a zinc finger protein and a cleavage domain or cleavage half-domain in conditions able to preserve cell viability. Polynucleotides encoding ZFNs, vectors comprising polynucleotides encoding ZFNs and cells comprising polynucleotides encoding ZFNs and/or cells comprising ZFNs 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.

主权项

1. A genetically modified cell comprising a genomic modification made by a nuclease, wherein the genomic modification is within an endogenous T-cell receptor (TCR) gene, and further wherein the genomic modification is selected from the group consisting of insertions, deletions and combinations thereof.