Sangamo Therapeutics, Inc.

Sangamo Biosciences, Inc.

Ospedale San Raffaele S.r.l.

Dow Agrosciences LLC

University of California

Whitehead Institute for Biomedical Research

Corteva Agriscience LLC

Lei Zhang

David Paschon

Jeffrey C Miller

Edward J Rebar

Philip D Gregory

Fyodor Urnov

Michael C Holmes

Siyuan Tan

Gregory J Cost

Dmitry Y Guschin

Luigi Naldini

Gary K Lee

Maria Chiara Bonini

Pietro Genovese

Josee Laganiere

Andreas Reik

Steven Robert Webb

Casey Christopher Case

Elena Provasi

Rudolf Jaenisch

Noriyuki Kasahara

Jayakumar Pon Samuel

W Michael Ainley

Anthony Conway

Thomas Wechsler

Zulma Magnani

Frank Soldner

Sara Mastaglio

H Steve Zhang

William M Ainley

Russell DeKelver

Pei-Qi Liu

Xiangdong Meng

Carolyn Dent

Steve H Zhang

Sumiti Jain

Ivan Krivega

Pon Samuel

Dmitry J Guschin

William Michael Ainley

H Steven Zhang

Disclosed herein are polypeptides, polynucleotides encoding, cells and organisms comprising novel DNA-binding domains, including TALE DNA-binding domains. Also disclosed are methods of using these novel DNA-binding domains for modulation of gene expression and/or genomic editing of endogenous cellular sequences.

DNA-binding proteins and uses thereof

Disclosed herein are methods and compositions for inactivating TCR and/or HLA 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.

Targeted disruption of T cell and/or HLA receptors

Methods and compositions for a genetic disease are provided.

Methods and compositions for treatment of a genetic condition

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.

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

Described herein are engineered nucleases comprising mutations in the cleavage domain (e.g., FokI or homologue thereof) and/or DNA binding domain (zinc finger protein, TALE, single guide RNA) such that on-target specificity is increased.

Engineered target specific nucleases

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.

Targeted disruption of the T cell receptor

Disclosed herein are methods and compositions for inactivating MEW 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.

Targeted disruption of the MHC cell receptor

Disclosed herein are compositions for linking DNA binding domains and cleavage domains (or cleavage half-domains) to form non-naturally occurring nucleases. Also described are methods of making and using compositions comprising these linkers.

Compositions for linking DNA-binding domains and cleavage domains

Disclosed herein are methods and compositions for insertion of transgene sequences encoding proteins that is aberrantly expressed in disease or disorder such as a lysosomal storage disease.

Methods and compositions for genome engineering

Described herein are compositions and methods for modulation of gene expression in the liver including modulation of PCSK9, TTR, SERPINA1, KLKB1 and/or HAO1.

Modulation of liver genes

Disclosed herein are methods and compositions for modifying TCR genes, using nucleases (zinc finger nucleases or TAL nucleases) to modify TCR genes.

Methods and compositions for gene disruption, gene editing or gene stacking within a FAD2 loci by cleaving, in a site directed manner, a location in a FAD2 gene in a soybean cell, to generate a break in the FAD2 gene and then optionally integrating into the break a nucleic acid molecule of interest is disclosed.

FAD2 performance loci and corresponding target site specific binding proteins capable of inducing targeted breaks

Disclosed herein are methods and compositions for inactivating MHC 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.

The present disclosure is in the field of genome engineering, particularly targeted modification of the genome of a hematopoietic stem cell.

Genetically modified human cell with a corrected mutant sickle cell mutation

Growing community of inventors

Richmond, CA, United States of America

Lei Zhang