The present invention relates to a polynucleotide configured for the treatment of a disease of retinal cone cells, such as achromatopsia, a nucleic acid vector comprising said polynucleotide, a pharmaceutical composition comprising said nucleic acid vector, a kit comprising said polynucleotide or said nucleic acid vector, a method of making said nucleic acid vector, and a method for treating a disease of the retinal cone cells.

The disclosure relates to methods for treating subjects with musculoskeletal diseases or with muscle wasting not associated with a musculoskeletal disease by gene transfer with recombinant adeno-associated viruses (rAAV) encoding myostatin inhibitors such as follistatin-344. The rAAV are administered prior to development of diffuse muscle fibrosis in a subject, or the rAAV administration avoids regions of muscle fibrosis in a subject.

The disclosure pertains to methods and compositions for treating disorders affecting the central nervous system (CNS). These disorders include neurometabolic disorders such as lysosomal storage diseases that affect the central nervous system, e.g., Niemann-Pick A disease. They also include disorders such as Alzheimer's disease. The disclosed methods involve contacting an axonal ending of a neuron with a composition containing high titer AAV carrying a therapeutic transgene so that the AAV vector is axonally transported in a retrograde fashion and transgene product is expressed distally to the administration site.

New gene therapy constructions and compositions are the subject of present invention. The gene therapy compositions consist in adeno-associated vectors which jointly express insulin (Ins) and glucokinase (Gck) genes. The new gene therapy constructions are useful for treatment of diabetes either in dosgs or human beings.

Expression of a phosphatase inhibitor in heart cells can be used to treat cardiac disorders, e.g., heart failure. Decreasing phosphatase activity can improve -adrenergic responsiveness.

The present invention relates to a method for inducing production of vascular endothelial growth factor (VEGF). The method includes administering, to an individual, a composition including adeno-associated virus (AAV) carrying a hPGIS gene coding for human prostacyclin synthase (hPGIS) which synthesizes prostaglandin I.sub.2 (PGI.sub.2).

Methods and therapeutics are provided for treating metabolic disorders by increasing activation of brown adipose tissue. Generally, the methods and therapeutics can increase activation of brown adipose tissue to increase energy expenditure and induce weight loss. In one embodiment, a method for increasing activation of brown adipose tissue includes modifying brown adipocytes to express a gene that activates brown adipocytes, such as uncoupling protein 1. In another embodiment, a method for increasing brown adipose tissue activation includes increasing the number of brown adipocytes. This can be accomplished by inducing proliferation of adipocytes in vivo or expanding adipocytes ex vivo, transplanting adipocytes into brown adipose tissue depots or elsewhere and inducing differentiation of adipocyte progenitor cells, such as MSCs, adipocyte progenitor cells, pre-adipocytes and adipocyte precursor cells.

Methods and compositions are provided for editing the genome of a cell without the use of an exogenously supplied nuclease. Aspects of the methods include contacting a cell with a targeting vector comprising nucleic acid sequence to be integrated into the target locus, where the cell is not also contacted with a nuclease. In addition, reagents, devices and kits thereof that find use in practicing the subject methods are provided.

This disclosure provides methods and compositions for treating disorders or injuries that affect motor function and control in a subject. In one aspect, the invention a transgene product is delivered to a subject's spinal cord by administering a recombinant neurotrophic viral vector containing the transgene to the brain. The viral vector delivers the transgene to a region of the brain which is susceptible to infection by the virus and which expresses the encoded recombinant viral gene product. Also provided are compositions for delivery of a transgene product to a subject's spinal cord by administering a recombinant neurotrophic viral vector containing the transgene to the subject's brain.

The present invention relates to a gene therapy vector which is useful in the treatment or prevention of hypertrophic cardiomyopathy in a subject in need thereof. The gene therapy vector of the invention comprises a nucleic acid sequence encoding a cardiac sarcomeric protein and a cardiomyocyte-specific promoter which is operably linked to said nucleic acid sequence. The invention furthermore relates to a cell which comprises the gene therapy vector. Pharmaceutical compositions which comprise the gene therapy vector and/or a cell comprising said vector are also provided. In another aspect, the invention relates to a method for treating or preventing hypertrophic cardiomyopathy in a subject by introducing the gene therapy vector of the invention into a subject in need of treatment.