EDITAS MEDICINE, INC.

Methods and compositions useful in targeting a payload to or editing target nucleic acid are disclosed herein. An isolated human hematopoietic stem cell (HSC) including a guide RNA (gRNA), wherein the gRNA comprises a targeting domain complementary to a target sequence, wherein the targeting domain is 20 nucleotides in length, wherein the targeting domain comprises three nucleotides modified with a 2′-O-methyl group within five nucleotides of the 5′ end of the targeting domain, wherein at least one of the three nucleotides is selected from the group consisting of 2′-O-methyl uridine, 2′-O-methyl cytidine and 2′-O-methyl adenosine, wherein the gRNA comprises two further nucleotides modified with a 2′ O-methyl group within five nucleotides of the 3′ end of the gRNA; and a Cas9 protein complexed to the gRNA is disclosed.

The present disclosure relates to CRISPR-related systems and components for targeting, editing, and/or modulating expression of a CD70 (Cluster of Differentiation 70) gene. The present disclosure also relates to methods and applications thereof in connection with engineered cells including T cells or T cell precursors.

CRISPR/Cas-related compositions and methods for treatment of Usher Syndrome and/or Retinitis Pigmentosa are disclosed herein.

Genome editing systems, guide RNAs, and CRISPR-mediated methods are provided for altering portions of the HBG1 and HBG2 loci, portions of the erythroid specific enhancer of the BCL11A gene, or a combination thereof, in cells and increasing expression of fetal hemoglobin.

Compositions and methods for treatment of CEP290 related diseases are disclosed.

CRISPR/CAS-related genome editing systems, compositions and methods for targeting the CBLB locus, as well as cells edited using these systems, compositions and methods are provided.

Compositions for use in treating subjects with USH2A-associated retinal and/or cochlear degeneration that result from mutations in exon 13 of the USH2A gene by deletion of exon 13 from the USH2A gene or transcripts, and methods of use thereof, as well as genetically modified animals and cells.

CRISPR/CAS-related compositions and methods for treatment of Primary Open Angle Glaucoma (POAG) are disclosed.

CRISPR/Cpf1-related compositions and methods for treatment of cancer.

Strategies, systems, compositions, and methods for genetically modifying cells to include one or more loss-of-function modifications and/or to include one or more gain-of-function modifications, as well as modified cells (and compositions of such cells) that include one or more loss-of-function modifications and/or that include one or more gain-of-function modifications, are described. In certain aspects, such modified cells include at least one gain-of-function modification within a coding region of an essential gene.