Abstract: Aspects of the invention described herein concern the incorporation of a FOXP3 cDNA (e.g., full-length human codon-optimized cDNA) into a FOXP3 gene or a non-FOXP3 locus so as to provide constitutive or regulated FOXP3 expression in a primary human CD34+ cells or cells derived from edited CD34+ cells. In some embodiments, guide RNA sequences that are directed to FOXP3, AAVS1, or other candidate loci are used for CRISPR/Cas9-mediated gene regulation, and gene delivery cassettes for HDR based gene-modification are provided.

Abstract: Aspects of the invention described herein concern the incorporation of a FOXP3 cDNA (e.g., full-length human codon-optimized cDNA) into a FOXP3 gene or a non-FOXP3 locus so as to provide constitutive or regulated FOXP3 expression in a primary human CD34+ cells or cells derived from edited CD34+ cells. In some embodiments, guide RNA sequences that are directed to FOXP3, AAVS1, or other candidate loci are used for CRISPR/Cas9-mediated gene regulation, and gene delivery cassettes for HDR based gene-modification are provided.

Abstract: The present disclosure provides improved genome editing compositions and methods for editing a human Wiskott-Aldrich syndrome gene. The disclosure further provides genome edited cells for the prevention, treatment, or amelioration of at least one symptom of WAS, including but not limited to, an immune system disorder, thrombocytopenia, eczema, X-linked thrombocytopenia (XLT), or X-linked neutropenia (XLN).

Abstract: The present disclosure provides improved genome editing compositions and methods for editing a human BTK gene. The disclosure further provides genome edited cells for the prevention, treatment, or amelioration of at least one symptom of X-linked agammaglobulinemia (XLA).

Abstract: Described herein are compositions, systems, and methods for treating, inhibiting, or ameliorating X-linked hyper IgM syndrome (X-HIGM) in subjects that have been identified or selected as being ones that would benefit from a therapy to treat, inhibit, or ameliorate X-HIGM. The systems include nuclease and vector donor constructs configured for co-delivery to modify endogenous CD40LG locus.

Abstract: Aspects of the invention described herein concern targeting of a FOXP3 cDNA, e.g., full-length human-codon optimized, into a FOXP3 locus or a non-FOXP3 locus so as to provide constitutive or regulated FOXP3 expression in a primary human lymphocyte. The compositions and materials described herein provide specificity for CRISPR/Cas-mediated gene regulation of murine, non-human primates or human FOXP3. Guide RNA sequences are used to target the FOXP3, AAVS1, and other candidate loci for CRISPR/Cas-mediated gene regulation, and gene delivery cassettes for HDR based gene-modification are provided. The alternative compositions described herein can be delivered in the form of Ribonucleoprotein (RNP) and may be used to target human and/or non-human primate FOXP3. Reagents are comprised of novel guide RNA sequences and can generate high frequency of on-target cleavage in combination with a Cas protein and novel gene delivery cassettes including FOXP3 cDNA+/?other cis linked gene products.

Abstract: The present disclosure provides improved genome editing compositions and methods for editing a human BTK gene. The disclosure further provides genome edited cells for the prevention, treatment, or amelioration of at least one symptom of X-linked agammaglobulinemia (XLA).

Abstract: Aspects of the invention described herein concern the incorporation of a FOXP3 cDNA (e.g., full-length human codon-optimized cDNA) into a FOXP3 gene or a non-FOXP3 locus so as to provide constitutive or regulated FOXP3 expression in a primary human CD34+ cells or cells derived from edited CD34+ cells. In some embodiments, guide RNA sequences that are directed to FOXP3, AAVS1, or other candidate loci are used for CRISPR/Cas9-mediated gene regulation, and gene delivery cassettes for HDR based gene-modification are provided.