Abstract: The present invention is related to the treatment of muscular dystrophy. In particular, compositions of short interfering ribonucleic acids (siRNAs) Eire contemplated that are targeted to different portions of a DUX4 messenger ribonucleic acid molecule. Preferably, these siRNAs are double stranded having a sense strand of fifteen (15) nucleotides. When applied as a therapeutic method, the short interfering ribonucleic acids reduce DUX4 protein translation and mediate a therapeutic response in human facioscapulohumeral muscular dystrophies, FSHD 1 and FSHD2.

Abstract: The present invention is related to the field of genetic engineering. In particular, the repair, reversion and/or conversion of genetic mutations that are linked to a muscular dystrophy disease. Specifically contemplated are gene editor nuclease proteins or base editor proteins that are targeted to the muscular dystrophy genetic mutations or pathogenic variants. Such gene editor nuclease proteins include, but are not limited to Cas12a nuclease proteins and adenine base editor proteins. Repair, reversion and/or disruption of the genetic mutation or pathogenic variant reduces at least one symptom of a muscular dystrophy disease.

Abstract: Human skeletal muscle stem cells were generated from facioscapulohumeral muscular dystrophy (FSHD) and healthy control iPSC using a transgene-free skeletal muscle differentiation protocol and production of stable iMyoblasts. Analyses revealed that FSHD and healthy control iMyoblasts are embryonic-like myogenic cells that undergo myotube differentiation ex vivo by growth factor depletion and are efficiently transplantable into the tibialis anterior (TA) muscles of NSG mice, where human muscle under-goes embryonic-to-adult myosin isoform switching. The DUX4 FSHD disease gene maintains its hypomethylated disease state inFSHD iPSC and iMyoblast, and its expression is upregulated during myotube differentiation and in muscle xenografts. Consequently, these iMyoblasts accurately exhibit the molecular pathology of human muscular dystrophies and are useful for the development of drug, gene editing and stem cell therapeutics.

Abstract: The present invention is directed to the filed of gene therapy. In particular, compositions and methods are disclosed that repair gene microduplication mutations by reversion to a wild type sequence. For example, the creation of a double stranded break by a programmable nuclease protein within a microduplication induces the microhomology mediated end joining DNA repair pathway that in the process of DNA repair removes the microduplication mutation and restores the wild type sequence.

Abstract: Compositions and methods for identifying new treatments for Facioscapulohumeral muscular dystrophy (FSHD), and uses thereof.

Abstract: Compositions and methods for identifying new treatments for Facioscapulohumeral muscular dystrophy (FSHD), and uses thereof.

Abstract: Compositions and methods for identifying new treatments for Facioscapulohumeral muscular dystrophy (FSHD), and uses thereof.

Abstract: Methods and compositions for inhibiting FGF signaling are described. Methods of the invention include contacting an FGF-responsive cell with exogenous heparan sulfate 6-O endosulfatase (Sulf1) in an amount effective to modify endogenous heparan sulfate, thereby inhibiting FGF signaling. Methods of the invention also include contacting an FGF-responsive cell with an exogenous Sulf1-modified compound, the exogenous Sulf1-modified compound being characterized by the ability to reduce binding of FGF2 or FGF4 to FGFR1. Compositions comprising exogenous Sulf1-modified compounds are also provided for use in conjunction with methods of the present invention.

Abstract: Nucleic acid sequences encoding members of a new subfamily of sulfatases and polypeptides encoded thereby are provided. Compositions and methods of modulating sulfatases of this new subfamily to modify growth properties and differentiation of cells, as well as the ability of cells to prevent viral entry and to prevent recruitment of lymphocytes to a site of inflammation are also provided. The compositions and methods are useful in treating cancer and inhibiting metastases, promoting differentiation of stem cells into muscle, neural and renal cells and inhibiting viral infection and inflammation. In addition, functional embryonic techniques for identification and characterization of developmental regulatory genes such as these sulfatases are provided.

Abstract: Nucleic acid sequences encoding members of a new subfamily of sulfatases and polypeptides encoded thereby are provided. Compositions and methods of modulating sulfatases of this new subfamily to modify growth properties and differentiation of cells, as well as the ability of cells to prevent viral entry and to prevent recruitment of lymphocytes to a site of inflammation are also provided. The compositions and methods are useful in treating cancer and inhibiting metastases, promoting differentiation of stem cells into muscle, neural and renal cells and inhibiting viral infection and inflammation. In addition, functional embryonic techniques for identification and characterization of developmental regulatory genes such as these sulfatases are provided.

Abstract: Nucleic acid sequences encoding members of a new subfamily of sulfatases and polypeptides encoded thereby are provided. Compositions and methods of modulating sulfatases of this new subfamily to modify growth properties and differentiation of cells, as well as the ability of cells to prevent viral entry and to prevent recruitment of lymphocytes to a site of inflammation are also provided. The compositions and methods are useful in treating cancer and inhibiting metastases, promoting differentiation of stem cells into muscle, neural and renal cells and inhibiting viral infection and inflammation. In addition, functional embryonic techniques for identification and characterization of developmental regulatory genes such as these sulfatases are provided.

Abstract: A transcription control element is provided for controlling gene expression in myogenic cells. The transcription control element comprises an isolated DNA segment having an enhancer activity in cultured cells and in non-cultured myogenic cells. The transcription control element is isolated from upstream regions of genes encoding bHLH myogenic regulatory proteins. Specifically, an enhancer element from the upstream region of human myoD and an enhancer element from the upstream region of a quail qmf1 are provided. These myoblast-specific transcription control elements are capable of significantly increasing the levels of gene expression in myogenic cells and are intended to be applied in gene therapy, using myoblast transfer and microinjection techniques, wherein myoblast-specific gene expression is desired or required.