Children's Medical Center Corporation

Massachusetts Institute of Technology

The Broad Institute, Inc.

University of Massachusetts

Daniel E Bauer

Stuart H Orkin

Jian Xu

Feng Zhang

Neville Espi Sanjana

Ophir Shalem

Scot Andrew Wolfe

Mehmet Fatih Bolukbasi

Jason Wright

Pengpeng Liu

Kevin Luk

Yuxuan Wu

Benjamin Roscoe

Jing Zeng

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 with a CAS9-CAS9 fusion for fetal hemoglobin reinduction

Provided herein are 2'-O-methyl 3&#x2032;phosphorothioate (MS)-modified synthetic nucleic acid molecules (single guide RNAs (sgRNAs)) for the use with a Cas9 nuclease in combination as a ribonucleoprotein (RNP) complex for an electroporation-based ex vivo targeted gene disruption of the BCL11A erythroid enhancer's +55, +58, or +62, functional regions. Additionally, provided herein are said RNP complexes (Cas9:MS-sgRNA), and compositions comprising the modified synthetic nucleic acid molecules or said RNP complexes, 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.

BCL11A guide delivery

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

Targeting BCL11A distal regulatory elements for fetal hemoglobin reinduction

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Cambridge, MA, United States of America

Daniel E Bauer