Targeted disruption of T cell receptor genes using engineered zinc finger protein nucleases

An isolated genetically modified cell comprising

• (i) a zinc finger nuclease (ZFN) comprising first and second ZFNs, each ZFN comprising a zinc finger protein (ZFP) that binds to a target site in an endogenous TCR gene, wherein the ZFN comprises:
• a first ZFP that binds to a target site within SEQ ID NO:1 and a second ZFP that binds to a target site within SEQ ID NO:7;
• a first ZFP that binds to a target site within SEQ ID NO:13 and a second ZFP that binds to a target site within SEQ ID NO:13;
• a first ZFP that binds to a target site within SEQ ID NO:29 and a second ZFP that binds to a target site within SEQ ID NO:23 or SEQ ID NO:34;
• a first ZFP that binds to a target site within SEQ ID NO:37 and a second ZFP that binds to a target site within SEQ ID NO:41;
• or
• a first ZFP that binds to a target site within SEQ ID NO:43 and a second ZFP that binds to a target site within SEQ ID NO:49 or SEQ ID NO:54;
• and
• (ii) wherein the endogenous TCR gene is inactivated by integration of a transgene into the endogenous TCR gene by the zinc finger nuclease at one or more of the target sites within SEQ ID NOS:
• 1 and 7;
• 13;
• 29 and 23, 29 and 34;
• 37 and 41;
• 43 and 49 or 43 and 54.