Sangamo Biosciences, Inc.

Sangamo Therapeutics, Inc.

Ospedale San Raffaele S.r.l.

University of Texas System

University of California

City of Hope

The Children's Hospital of Philadelphia

University of Southern California

Fondazione Telethon

Sigma-aldvich Co. LLC

Whitehead Institute for Biomedical Research

Sigma-aldrich Co. LLC

Fondazione Centro San Raffaele Del Monte Tabor

Michael C Holmes

Philip D Gregory

Fyodor Urnov

David Paschon

Jeffrey C Miller

Andreas Reik

Lei Zhang

Edward J Rebar

Gregory J Cost

Dale Ando

Luigi Naldini

Jianbin Wang

Pietro Genovese

Gary Ka Leong Lee

Maria Chiara Bonini

Xiangdong Meng

Matthew C Mendel

Michael C Jensen

Dmitry Y Guschin

Trevor Collingwood

Laurence J N Cooper

Russell DeKelver

Carl O Pabo

Elena Provasi

Katherine A High

Noriyuki Kasahara

Yannick Doyon

Anthony Conway

Tianjian Li

Thomas Wechsler

Brigit E Riley

Angelo Leone Lombardo

Josee Laganiere

Dmitry M Guschin

Zulma Magnani

Shuyuan Yao

Hojun Li

Sara Mastaglio

Rudolf Jaenisch

Gregory D Davis

Paula M Cannon

Phillip Tam

Frank Soldner

Laurence Jn Cooper

Xiaoxia Cui

Dirk Hockemeyer

Edward J Weinstein

Yann Jouvenot

Colin Michael Exline

Rudolf Jaenish

Russell Dekelver

Sean M Brennan

Laurence J Cooper

Gary Ka Lee

Disclosed herein are methods and compositions for inactivation of the human glucocorticoid receptor (GR) gene by targeted cleavage of genomic DNA encoding the GR. Such methods and compositions are useful, for example, in therapeutic applications which require retention of immune function during glucocorticoid treatment.

Method of inactivating a glucocorticoid receptor gene in an isolated cell

Nucleases and methods of using these nucleases for expressing an antibody from a safe harbor locus in a secretory tissue, and clones and animals derived therefrom.

Methods and compositions for engineering immunity

Disclosed herein are methods and compositions for inactivating CCR-5 genes, using zinc finger nucleases (ZFNs) comprising a zinc finger protein and a cleavage domain or cleavage half-domain. Polynucleotides encoding ZFNs, vectors comprising polynucleotides encoding ZFNs, such as adenovirus (Ad) vectors, and cells comprising polynucleotides encoding ZFNs and/or cells comprising ZFNs are also provided.

Methods and compositions for gene inactivation

Disclosed herein are methods and compositions for targeted, nuclease-mediated insertion of transgene sequences into the genome of a cell.

Method of making and using mammalian liver cells for treating hemophilia or lysosomal storage disorder

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

Disclosed herein are methods and compositions for targeted cleavage of a genomic sequence, targeted alteration of a genomic sequence, and targeted recombination between a genomic region and an exogenous polynucleotide homologous to the genomic region. The compositions include fusion proteins comprising a cleavage domain (or cleavage half-domain) and an engineered zinc finger domain and polynucleotides encoding same. Methods for targeted cleavage include introduction of such fusion proteins, or polynucleotides encoding same, into a cell. Methods for targeted recombination additionally include introduction of an exogenous polynucleotide homologous to a genomic region into cells comprising the disclosed fusion proteins.

Methods and compositions for targeted cleavage and recombination

Disclosed herein are methods and compositions for modulating expression of a PD1 gene.

Methods and compositions for modulating PD1

Methods and compositions for modifying T-cells in which PD1 and/or CTLA-4 is repressed and/or inactivated using fusion proteins such as artificial transcription factors and nucleases.

T cell modifying compounds and uses thereof

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

Isolated human cell with an inactivated glucocorticoid receptor gene

Disclosed herein are methods and compositions for modulating the expression of a HLA locus or for selectively deleting or manipulating a HLA locus or HLA regulator.

Methods and compositions for modification of a HLA locus

Described herein are methods of expressing nucleic acids in T cells pre-exposed to a co-stimulatory signal and then transduced with adenoviral vectors. In some embodiments, the co-stimulation is provided by anti-CD3 and anti-CD28 antibodies and the adenoviral vector is pseudotyped for T-cell entry. The invention also relates to compositions for carrying out these methods, provided as kits or pharmaceutical compositions that can be used to treat diseases including immunological conditions and hematological malignancies.

Methods and compositions for increased transgene expression

Growing community of inventors

Richmond, CA, United States of America

Michael C Holmes