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

US8956828B2 · kind B2 · utility

Assignees

• Sangamo Biosciences, Inc. · US
• OSPEDALE SAN RAFFAELE S.R.L. · IT

Inventors

• Maria Chiara Bonini · Milano, IT
• Pietro Genovese · Messina, IT
• Philip D. Gregory · Richmond, US
• Michael C. Holmes · Richmond, US
• Luigi Naldini · Torino, IT
• David Paschon · Oakland, US
• Elena Provasi · Rescaldina, IT
• Lei Zhang · Beijing, CN

Key dates

• Filing date: Nov 10, 2010
• Grant date: Feb 17, 2015
• Expiry date: Jun 27, 2032

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07K2319/95
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

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.