The present invention relates to a method for treating ocular disease in a subject in need thereof comprising a step of administering to said subject a therapeutically amount of an inhibitor of SOX21 gene expression and/or activity. By studying a mouse model of congenital microcoria, the inventors demonstrate that this ultra-rare and purely ocular disease is due to unanticipated complex mechanisms linked with 3D regulation of gene expression. They propose that the disease is due to the illegitimate expression of a transcription factor, SOX21, induced by the adoption of a DCT enhancer(s). They show that SOX21 binds to a regulatory region of the Tgfβ2 gene and the inventors demonstrate overexpression of this trophic factor in the iris and accumulation of its product in the aqueous humor of the mouse carrying the minimal MCOR deletion which recapitulates the observed accumulation in patients with POAG and one of our patient with MCOR.

The instant invention provides for novel catiomc lipids that can be used in combination with other lipid components such as cholesterol and PEG-lipids to form lipid nanoparticles with oligonucleotides. It is an object of the instant invention to provide a cationic lipid scaffold that demonstrates enhanced efficacy along with lower liver toxicity as a result of lower lipid levels in the liver. The present invention employs low molecular weight cationic lipids with one short lipid chain to enhance the efficiency and tolerability of in vivo delivery of siRNA.

The invention provides an isolated and purified nucleic acid sequence encoding a chimeric antigen receptor (CAR) directed against B-cell Maturation Antigen (BCMA). The invention also provides host cells, such as T-cells or natural killer (NK) cells, expressing the CAR and methods for destroying multiple myeloma cells.

The present invention relates to regulatory nucleic acid sequences, in particular muscle-specific promoters, elements thereof, and other such nucleic acid sequences, that are capable of enhancing muscle-specific expression of genes. The invention also relates to expression constructs, vectors and cells comprising such muscle-specific regulatory nucleic acid sequences, and to methods of their use. The regulatory nucleic acid sequences are of particular utility for gene therapy applications, but also find utility in other areas such as bioprocessing and biotechnology.

CRISPR/Cas-related compositions and methods which provide for efficient gene editing of eukaryotic cells using modified gRNAs.

The present invention includes methods and compositions for elimination of polyomaviruses, such as John Cunningham Virus (JVC), from host cells, and the treatment of polyomavirus related diseases, such as progressive multifocal leukoencephalopathy (PML). The compositions include isolated nucleic acid sequences comprising an CRISPR-associated endonuclease and a guide RNA, wherein the guide RNA is complementary to a target sequence in a polyomavirus.

The present invention provides modified stem cells (SCs) and use of the SCs to treat disease.

The present disclosure describes the generation and the use of Ad variants (Ad) possessing any combination of mutations in genes that code for the hexon, penton, fiber, and non-structural proteins, where simultaneous modification of hexon and penton are made to avoid the trapping of Ad in the liver and to reduce toxicity after intravascular virus administration. Such liver de-targeted Ad can be useful tool for selective and specific gene delivery to extra-hepatic tissues and cells, including disseminated metastatic cancer cells.

The present disclosure describes the generation and the use of Ad variants (Ad) possessing any combination of mutations in genes that code for the hexon, penton, fiber, and non-structural proteins, where simultaneous modification of hexon and penton are made to avoid the trapping of Ad in the liver and to reduce toxicity after intravascular virus administration. Such liver de-targeted Ad can be useful tool for selective and specific gene delivery to extra-hepatic tissues and cells, including disseminated metastatic cancer cells.

The invention provides for recombinant AAV vectors comprising a polynucleotide sequence comprising the guide strand of miR-29c and methods of using the recombinant vectors to reduce or prevent fibrosis in subjects suffering from muscular dystrophy.