The present disclosure provides codon optimized nucleotide sequences encoding human alpha-galactosidase A, vectors, and host cells comprising codon optimized alpha-galactosidase A sequences, and methods of treating disorders such as Fabry disease comprising administering to the subject a codon optimized sequence encoding human alpha-galactosidase A.

Gene therapy compositions and methods are provided for targeting an ATP binding cassette subfamily A member 4 (ABCA4), or a functional fragment thereof, in a patient, thereby treating or mitigating Inherited Macular Degenerations including a Stargardt disease or other diseases that involve retinal degeneration.

A method of treating an inherited retinal disease (IRD) associated with a pathogenic point mutation in a mutant allele of an IRD-related gene in the retina or the retinal pigment epithelium (RPE) of a subject in need thereof includes base editing the pathogenic point mutation in the retinal cell or retinal pigment epithelium cell to correct the pathogenic mutation, generate a non-pathogenic point mutation, or modulate expression of an IRD-related gene and restore visual function of subject.

The invention provides compositions and methods for treating neuropathic pain. Specifically, the disclosure provides a polynucleotide comprising a trigeminal ganglion (TGG) or dorsal root ganglion (DRG) promoter operably linked to a recombinant nucleic acid encoding an endonuclease that binds to a nucleotide sequence in the human colony stimulating factor 1 (hCSF1) gene and a method of using the polynucleotide or a vector comprising the polynucleotide for treatment of neuropathic pain.

The present invention relates to the use of gasdermin, in particular of gasdermin A, gasdermin B, gasdermin C, gasdermin D, DFNA5 or DFNB59 (or pejvakin), and more particularly pejvakin for modulating cellular redox homeostasis. A particularly preferred use of gasdermin, in particular of gasdermin A, gasdermin B, gasdermin C, gasdermin D, DFNA5 or DFNB59 (or pejvakin), and more particularly pejvakin in the context of the present invention is as an antioxidant. The present invention also concerns a virally-mediated gene therapy for restoring genetically-impaired auditory and vestibular functions in subjects suffering from an Usher syndrome. More precisely, this gene therapy takes advantage of an AAV2/8 vector expressing at least one USH1 gene product, preferably SANS.

Described herein are methods of preventing, arresting progression of or ameliorating vision loss and other conditions associated with Leber congenital amaurosis (LCA) in a subject. The methods include administering to said subject an effective concentration of a composition comprising a recombinant adeno-associated virus (AAV) carrying a nucleic acid sequence encoding a normal NPHP5 protein, or fragment thereof, under the control of regulatory sequences which express the NPHP5 protein in the photoreceptor cells of the subject, and a pharmaceutically acceptable carrier.

Provided are methods of transducing hair cells of the inner ear in a subject comprising administering to the subject an adeno-associated viral (AAV) vector comprising a nucleic acid sequence encoding a capsid comprising the amino acid sequence of SEQ ID NO: 1, wherein the AAV vector further comprises a heterologous nucleic acid sequence. Additionally, methods of treating, preventing, or inhibiting a cochlear disorder or balance disorder in a subject comprising administering the AAV vector to the subject are provided.

The present invention relates to a pharmaceutical composition comprising a modified mRNA that is stabilised by sequence modifications and optimised for translation. The pharmaceutical composition according to the invention is particularly well suited for use as an inoculating agent, as well as a therapeutic agent for tissue regeneration. In addition, a process is described for determining sequence modifications that promote stabilisation and translational efficiency of modified mRNA of the invention.

The present application describes an antibody-coding, non-modified or modified RNA and the use thereof for expression of this antibody, for the preparation of a pharmaceutical composition, in particular a passive vaccine, for treatment of tumours and cancer diseases, cardiovascular diseases, infectious diseases, autoimmune diseases, virus diseases and monogenetic diseases, e.g. also in gene therapy. The present invention furthermore describes an in vitro transcription method, in vitro methods for expression of this antibody using the RNA according to the invention and an in vivo method.

The present invention relates to recombinant adeno-associated virus (rAAV) delivery of an alpha-sarcoglycan gene. The invention provides rAAV products and methods of using the rAAV in the treatment of limb girdle muscular dystrophies such as LGMD2D.