Compositions and methods for using actin-based peptides to modulate cellular bioactivity, including modulation of cellular susceptibility to intracellular pathogens, such as bacteria and viruses.

Disclosed are compositions and methods for treating dystrophinopathies. Compositions include modified dystrophin polynucleotides that encode modified dystrophin proteins having modified hinge 1 (H1) and/or hinge 4 (H4). Also disclosed are methods for treating dystrophinopathies by administering compositions encoding modified dystrophin proteins having modified hinge 1 (H1) and/or modified hinge 4 (H4).

The present disclosure provides materials and methods for treating a patient with Duchenne Muscular Dystrophy (DMD), e.g., through ex vivo and in vivo methods of genome editing. The present disclosure also relates to methods and compositions for use of self-inactivating/self-targeting CRISPR/Cas or CRISPR/Cpf1 systems to genetically modify cells, e.g., to modulate the expression, function, and/or activity of the dystrophin gene.

The invention provides means and methods for alleviating one or more symptom(s) of Duchenne Muscular Dystrophy and/or Becker Muscular Dystrophy. Therapies using compounds for providing patients with functional muscle proteins are combined with at least one adjunct compound for reducing inflammation, preferably for reducing muscle tissue inflammation, and/or at least one adjunct compound for improving muscle fiber function, integrity and/or survival.

Methods and compositions for treating a disorder of cardiac muscle and/or skeletal muscle in a subject according to aspects of the present disclosure. Treatment methods include administering a therapeutically effective dose of a C-terminal portion of troponin I capable of reducing sensitivity of cardiac muscle and/or skeletal muscle to Ca.sup.2+ without decreasing maximum force production. Assays for identification of compounds capable of reducing sensitivity of cardiac muscle and/or skeletal muscle to Ca.sup.2+ without decreasing maximum force production are further provided.

Provided herein are methods of inhibiting type 1 receptor and/or type 2 receptor signaling in subjects, optionally subjects with diseases associated with myostatin, type 1 receptor, and/or type 2 receptor signaling, or muscle loss and/or bone deterioration. Also provided are compositions for inhibition of type 1 receptor and/or type 2 receptor signaling.

The present disclosure provides methods for generating induced cardiomyocytes and/or inducing a cardiomyocyte phenotype in cells in vivo or in vitro, such as by expression of ASCL1 or MYF6 and MYOCD. The present disclosure further provides gene-delivery vectors comprising one or more polynucleotides selected from ASCL1, MYF6, MYOCD, MEF2C, and TBX5. It further provides compositions comprising induced cardiomyocytes and provides methods of treating a heart condition, such as myocardial infarction. The disclosure also provides engineered myocardin proteins with an internal deletion, vectors encoding such engineered mycocardins, and methods of use thereof.

The present disclosure provides methods for generating induced cardiomyocytes and/or inducing a cardiomyocyte phenotype in cells in vivo or in vitro, such as by expression of ASCL1 or MYF6 and MYOCD. The present disclosure further provides gene-delivery vectors comprising one or more polynucleotides selected from ASCL1, MYF6, MYOCD, MEF2C, and TBX5. It further provides compositions comprising induced cardiomyocytes and provides methods of treating a heart condition, such as myocardial infarction. The disclosure also provides engineered myocardin proteins with an internal deletion, vectors encoding such engineered mycocardins, and methods of use thereof.

A composition comprising a gene therapy product for use in the treatment of a dystrophic disease in a subject, advantageously in humans, wherein:

the gene therapy product comprises a nucleic acid sequence encoding a functional microdystrophin;

the composition is systemically administered.

The present disclosure relates generally to methods of treating a subject having muscular dystrophy or DMD. The present disclosure also relates generally to methods of prophylactically treating a subject at risk of developing muscular dystrophy or DMD. In some embodiments, the methods may include administering a pharmaceutical composition including an RRM1 gene, an RRM2 gene, and a delivery vehicle to a subject. In another embodiment, the methods may include administering a pharmaceutical composition including an RRM1 gene and an RRM2 gene coupled to a regulatory cassette to a subject. In yet another embodiment, the methods may include administering a pharmaceutical composition including an RRM 1 gene, an RRM2 gene, a regulatory cassette, and a delivery vehicle to a subject.