Sangamo Therapeutics, Inc.

Sangamo Biosciences, Inc.

University of California

Dow Agrosciences LLC

Gregory J Cost

Fyodor Urnov

Edward J Rebar

Michael C Holmes

Jeffrey C Miller

Andreas Reik

Anthony Conway

Lei Zhang

David Paschon

Philip D Gregory

H Steve Zhang

Trevor Collingwood

Jianbin Wang

Russell DeKelver

Dmitry Y Guschin

Dmitry M Guschin

Noriyuki Kasahara

Josee Laganiere

Steven Robert Webb

Joseph F Petolino

Lakshmi Sastry-Dent

Jayakumar Pon Samuel

W Michael Ainley

William M Ainley

Thomas Wechsler

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 enhancing insertion of transgene sequences encoding proteins that is aberrantly expressed in disease or disorder such as a lysosomal storage disease or a hemophilia by administering one or more topoisomerases inhibitors, one or more stabilizers of R loop formation or inhibitors of R-loop repair and/or one or more up-regulators of the TC-NER pathway to the target cell.

Methods and compositions for enhancing targeted transgene integration

Nucleases and methods of using these nucleases for genetic alteration of red blood cells (RBCs), for example for providing for a protein lacking in a monogenic disorder or a biologic for the treatment of exposure to a toxin using genetically altered RBCs.

Methods and compositions for delivery of biologics

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

Methods and compositions comprising a CRISPR/Cas nuclease that cleaves a BCL11A gene for the modification of the BCL11A gene and for modification of globin expression.

Methods and compositions comprising a CRISPR/Cas nuclease that cleaves a T cell receptor (TCR) gene and/or human leukocyte (HLA) gene, the nuclease comprising a cleavage domain and a single guide RNA that binds to a target site in the TCR and/or HLA gene.

Methods and compositions for increasing transgene expression and/or activity, including for increasing nuclease-mediated genomic modifications.

Methods and compositions for increasing transgene activity

Disclosed herein are methods and compositions for homology-independent targeted insertion of donor molecules into the genome of a cell.

Methods and compositions for nuclease-mediated targeted integration of transgenes

Disclosed herein are donor molecules comprising single-stranded complementary regions flanking one or more sequences of interest. The donor molecules and/or compositions comprising these molecules can be used in methods for targeted integration of an exogenous sequence into a specified region of interest in the genome of a cell.

Targeted genomic modification with partially single-stranded donor molecules

Disclosed herein are nucleases and methods of using these nucleases for alteration of a globin gene and generation of cells.

Methods and compositions comprising a fusion protein comprising a Cas protein and a functional domain in association with a single guide RNA targeted to an endogenous gene for genetic alteration of cells are provided.

Disclosed herein are methods and compositions for inactivating a FUT8 gene, using fusion proteins comprising a zinc finger protein and a cleavage domain or cleavage half-domain. Polynucleotides encoding said fusion proteins are also provided, as are cells comprising said polynucleotides and fusion proteins.

Methods and compositions for inactivating alpha 1,6 fucosyltransferase (FUT8) gene expression

Methods and compositions comprising single guide RNAs targeted to an endogenous mammalian &#x3b2; globin gene (HBB), gamma globin gene (HBG1), B-cell lymphoma/leukemia 11A (BCL11A) gene, Kruppel-like factor 1 (KLF1) gene, CCR5 gene, CXCR4 gene, PPP1R12C (AAVS1) gene, hypoxanthine phosphoribosyltransferase (HPRT) gene, albumin gene, Factor VIII gene, Factor IX gene, Leucine-rich repeat kinase 2 (LRRK2) gene, Hungtingin (Htt) gene, rhodopsin (RHO) gene, Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene, surfactant protein B gene (SFTPB), T-cell receptor alpha (TRAC) gene, T-cell receptor beta (TRBC) gene, programmed cell death 1 (PD1) gene, Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) gene, human leukocyte antigen (HLA) A gene, a LMP7 gene, a Transporter associated with Antigen Processing (TAP) gene, tapasin gene (TAPBP), a class II major histocompatibility complex transactivator (CIITA) gene, a dystrophin gene (DMD), a glucocorticoid receptor gene (GR), IL2RG gene or RFX5 for genetic alteration of cells are provided.

The present disclosure is in the field of genome engineering, particularly targeted integration of a functional SCID-related genes (e.g., IL2RG, RAG1 and/or RAG2 gene) into the genome of a cell for provision of proteins lacking or deficient in SCID.

Growing community of inventors

Richmond, CA, United States of America

Gregory J Cost