Children's Medical Center Corporation

Harvard College

Massachusetts Institute of Technology

The Broad Institute, Inc.

Dana-farber-cancer Institute Inc.

Sangamo Therapeutics, Inc.

Xu, Jian

Orkin, Stuart H.

Cong, Peng

Stuart H Orkin

Daniel E Bauer

Vijay G Sankaran

Jian Xu

Feng Zhang

Neville Espi Sanjana

Ophir Shalem

Fyodor Urnov

Loren D Walensky

Gregory H Bird

Andreas Reik

David Ginsburg

Randal J Kaufman

Jason Wright

Woojin Kim

Cong Peng

The application relates to a deep scanning mutagenesis library to interrogate phenotypic changes in a population of cells comprising a plurality of CRISPR-Cas system guide RNAs targeting genomic sequences within at least one continuous genomic region, wherein the guide RNAs target at least 100 genomic sequences upstream of a PAM sequence for every 1000 base pairs within the continuous genomic region and methods for their use.

Functional genomics using CRISPR-Cas systems for saturating mutagenesis of non-coding elements, compositions, methods, libraries and applications thereof

Provided herein are nucleic acid molecules that target the BCL11A enhancer functional regions, compositions comprising the nucleic acid molecules and methods for increasing fetal hemoglobin levels in a cell by disrupting BCL11A expression at the genomic level. Also provided herein are methods and compositions relating to the treatment of hemoglobinopathies by reinduction of fetal hemoglobin levels. In particular, the nucleic acid molecules target the +62, +58, and/or the +55 enhancer functional regions.

Targeting BCL11A enhancer functional regions for fetal hemoglobin reinduction

Provided herein are methods and compositions for increasing fetal hemoglobin levels in a cell by disrupting BCL11A expression at the genomic level. Also provided herein are methods and compositions relating to the treatment of hemoglobinopathies by reinduction of fetal hemoglobin levels.

Targeting BCL11A distal regulatory elements for fetal hemoglobin reinduction

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

Nuclease-mediated regulation of gene expression

The invention relates to methods and uses of modulating fetal hemoglobin expression (HbF) in a hematopoietic progenitor cells via inhibitors of BCL11A expression or activity, such as RNAi and antibodies.

Modulation of BCL11A for treatment of hemoglobinopathies

Provided herein are polypeptides containing stabilized therapeutic peptides related to enhancer of zeste homolog 2 (EZH2), histone lysine N-methyltransferase. Also provided are compositions containing these polypeptides and methods of using such peptides in the treatment of cancer that include administering to a subject one of the polypeptides.

Stablized EZH2 peptides

Von Willebrand's Factor (VWF) is produced using an expression vector that includes: 1) a DNA sequence encoding a functional VWF protein; and 2) regulatory DNA capable of effecting expression of that DNA sequence in a host cell transformed with the vector. Restriction fragment length polymorphisms (RFLP's) associated with the VWF gene are identified and used in a probe for determining the source of a VWF gene in a DNA sample. The gene for VWF is localized to the short arm of human chromosome 12 (12p).

DNA encoding Von Willebrand Factor (VWF) and methods and cells for producing VFW, and VFW produced by the DNA, methods and cells

Growing community of inventors

Brookline, MA, United States of America

Stuart H Orkin