Abstract: The present disclosure relates generally to novel lipid nanoparticle (LNP)-based compositions useful for, e.g., the delivery of a site-specific endonuclease or a nucleic acid molecule encoding same, into a target cell. Some embodiments of the disclosure relate to compositions and methods for editing the genome of a cell, which involve contacting the cell with an LNP composition as described herein.

Abstract: The present application provides materials and methods for treating a patient with autosomal dominant RP, both ex vivo and in vivo; materials and methods for editing a RHO gene in a human cell; and materials and methods for editing a P23H mutation in a RHO gene in a human cell. In addition, the present application provides one or more gRNAs or sgRNAs for editing a RHO gene; one or more gRNAs or sgRNAs for editing a P23H mutation in a RHO gene; and a therapeutic comprising at least one or more gRNAs or sgRNAs for editing a P23H mutation in a RHO gene. The present application provides a therapeutic for treating a patient with autosomal dominant RP. The present application provides a kit for treating a patient with autosomal dominant RP. In addition, the present application provides a self-inactivating CRISPR-Cas system.

Abstract: The disclosure features methods and compositions for differentiating stem cells into hematopoietic stem and progenitor cells (HSPC) and/or Natural Killer (NK) cells. The methods and compositions described herein are used to differentiate stem or progenitor cells having at least one gene-edit that is maintained in the differentiated cell. Also provided are differentiated cells produced using the methods and compositions described herein for therapeutic applications.

Abstract: Provided herein, in some embodiments, are methods and compositions (e.g., cell compositions) for the treatment of cancer.

Abstract: Provided include compositions, methods, and systems for modulating the expression, function, and/or activity of a target gene, for example a blood-clotting protein such as Factor VIII (FVIII), in a cell by genome editing. Also provided include compositions, methods, and systems for treating a subject having or suspected of having a disorder or health condition, e.g., Hemophilia A, employing ex vivo and/or in vivo genome editing.

Abstract: The present application provides materials and methods for treating a patient with Usher Syndrome Type 2A, both ex vivo and in vivo; materials and methods for editing a USH2A gene in a human cell; materials and methods for editing an USH2A gene containing an IVS40 mutation; materials and methods for treating a patient with an USH2A gene containing an IVS40 mutation; and a method for deleting a sequence comprising an IVS40 mutation within a USH2A gene of a cell. The present application also provides one or more gRNAs or sgRNAs for editing an USH2A gene containing an IVS40 mutation. The present application provides a therapeutic for treating a patient with Usher Syndrome Type 2A. The present application also provides a kit for treating a patient with Usher Syndrome Type 2A.

Abstract: Aspects of this invention, inter alia, relate to novel systems for targeting, editing or manipulating DNA in a cell, using novel synthetic RNA-guided nucleases (sRGNs). The sRGNs are derived from wildtype or parental small type II CRISPR Cas9 endonucleases.

Abstract: Materials and methods for treating a patient with hereditary hemochromatosis (HHC), both ex vivo and in vivo, and materials and methods for modulating the expression, function, or activity of a haemochromatosis (HFE) gene in a cell by genome editing.

Abstract: The present disclosure provides optimized mRNAs encoding a site-directed endonuclease for use in a CRISPR/Cas system. Also provided herein are delivery systems for use of the CRISPR/Cas system in methods of in vivo and ex vivo genome editing.

Abstract: The present application provides a CRISPR/Cas system comprising a nuclease segment that encodes a Cas9 nuclease or variant thereof, a guide RNA segment comprising a nucleotide sequence that encodes a gRNA or sgRNA, and a promoter segment comprising a nucleotide sequence that encodes a first promoter comprising one or more tetracycline operator sequence, wherein the gRNA segment is operably linked to the promoter segment. The present application also provides materials and methods for controlling transcriptional expression of guide RNAs and/or post-transcriptional expression of Cas nuclease.

Abstract: The present application provides materials and methods for treating a patient with one or more of Usher Syndrome Type 2A and ARRP, both ex vivo and in vivo; materials and methods for editing an USH2A gene containing a guanine deletion at nucleotide position c.2299. In addition, the present application provides one or more gRNAs or sgRNAs for editing an USH2A gene containing a guanine deletion at nucleotide position c.2299; a therapeutic comprising at least one or more gRNAs or sgRNAs for editing an USH2A gene containing a guanine deletion at nucleotide position c.2299; and a therapeutic for treating a patient with one or more of Usher Syndrome Type 2A and ARRP. The present application also provides a kit for treating a patient with one or more of Usher Syndrome Type 2A and ARRP.

Abstract: The present disclosure relates to methods, compositions and kits for treating conditions that are related with angiopoietin-like 3 (ANGPTL3) by gene editing.

Abstract: Provided herein, in some embodiments, are materials and methods for treating hemophilia A in a subject ex vivo or in vivo. Also provided herein, in some embodiments, are materials and methods for knocking in a coding sequence encoding a synthetic FVIII having a B domain substitute into a genome.

Abstract: The invention provides compositions and methods useful for the depletion of CD117+ cells and for the treatment of various hematopoietic diseases, metabolic disorders, cancers, e.g., acute myeloid leukemia (AML) and autoimmune diseases, among others. Described herein are antibodies, antigen-binding fragments, and conjugates thereof that can be applied to effect the treatment of these conditions, for instance, by depleting a population of CD117+ cells in a patient, such as a human. The compositions and methods described herein can be used to treat a disorder directly, for instance, by depleting a population of CD117+ cancer cells or autoimmune cells. The compositions and methods described herein can also be used to prepare a patient for hematopoietic stem cell transplant therapy and to improve the engraftment of hematopoietic stem cell transplants by selectively depleting endogenous hematopoietic stem cells prior to the transplant procedure.

Abstract: Masked chimeric antigen receptor (CAR) constructs comprising an extracellular antigen binding domain specific tyrosine-protein kinase-like 7 (PTK7), which is linked to a mask peptide that blocks binding of masked CAR from binding to PTK7. Also provided herein are genetically engineered T cells expressing a masked CAR specific to PTK7 and therapeutic uses thereof.

Abstract: The present application provides materials and methods for treating a patient with one or more conditions associated with ANGPTL3 whether ex vivo or in vivo. In addition, the present application provides materials and methods for editing and/or modulating the expression of ANGPTL3 gene in a cell by genome editing.

Abstract: The present application provides materials and methods for treating a patient with Glycogen Storage Disease type 1a (GSD1a) both ex vivo and in vivo. In addition, the present application provides materials and methods for modulating the expression, function, and/or activity of the glucose-6-phosphatase, catalytic (G6PC) and/or the glucose-6-phosphatase (G6Pase) protein in a cell by genome editing.

Abstract: A population of genetically engineered T cells, comprising a disrupted Reg1 gene and/or a disrupted TGFBRII gene. Such genetically engineered T cells may comprise further genetic modifications, for example, a disrupted CD70 gene. The population of genetically engineered T cells exhibit one or more of (a) improved cell growth activity; (b) enhanced persistence; and (c) reduced T cell exhaustion, (d) enhanced cytotoxicity activity, (e) resistant to inhibitory effects induced by TGF-b, and (f) resistant to inhibitory effects by fibroblasts and/or inhibitory factors secreted thereby, as compared to non-engineered T cell counterparts.

Abstract: The present application provides materials and methods for treating a patient with Alpha-1 antitrypsin deficiency (AATD) both ex vivo and in vivo. In addition, the present application provides materials and methods for editing the SERPINA1 gene in a cell by genome editing.

Abstract: The present application provides materials and methods for treating a patient with Amyotrophic Lateral Sclerosis (ALS). In addition, the present application provides materials and methods for (1) modifying the transcription start site of exon1a to render the transcription start site non-functioning, (2) deleting the transcription site of exon1a, (3) deleting exon1a, or (4) deleting of the expanded hexanucleotide repeat within or near the C9ORF72 gene, or any combinations of (1)-(4), above in a cell by genome editing.