The present invention provides an isolated nucleic acid molecule comprising, or consisting of, the nucleic acid sequence of SEQ ID NO:1 or a nucleic acid sequence of at least 400 bp having at least 80% identity to said sequence of SEQ ID NO:1, wherein said isolated nucleic acid molecule specifically leads to the expression in direction selective retinal ganglion cells of a gene when operatively linked to a nucleic acid sequence coding for said gene.

The present invention is directed to small interfering RNA molecules (siRNA) targeted against nucleic acid sequence that encodes huntingtin or ataxin-1, and methods of using these siRNA molecules.

Methods and compositions for the prevention and treatment of liver damage or disease in a subject in need thereof are provided. The methods involve providing the sulfated oxysterol 25-hydroxycholesterol-3-sulfate (25HC3S) to the subject e.g. by 1) administering 25HC3S to the subject; or 2) overexpressing, in the subject, the hydroxysterol sulfotransferase enzyme SULT2B1b, which catalyzes the sulfation of 25-hydroxycholesterol (25HC) to form 25HC3S.

Provided herein is a method of delivering nucleic acid molecules to a compartmentalized tissue or organ of a subject. Also provided herein are uses and processes for delivering a nucleic acid molecule to the parenchyma of a compartmentalized tissue or organ. The methods and uses can be used in the treatment of diseases and conditions and in industrial, agricultural and veterinary applications. Also provided herein are compositions containing an adenovirus or adeno-associated virus or other recombinant virus formulated for administration to the parenchyma of a tissue or organ.

Methods of treating an adult mammal for an aging-associated impairment are provided. Aspects of the methods include modulating CCR3, e.g., by modulating eotaxin-1/CCR3 interaction, in the mammal in a manner sufficient to treat the mammal for the aging-associated impairment. A variety of aging-associated impairments may be treated by practice of the methods, which impairments include cognitive impairments.

Several embodiments disclosed herein relate generally to methods and compositions for the generation of biological pacemakers. In some embodiments, the methods comprise contacting non-pacemaker cells with one or more transcription factors (in vivo or in vitro) and inducing pacemaker functionality in the cells.

The disclosure relates to optimized polynucleotide sequences for LAMP-2B, expression cassettes, vectors, and methods of use thereof in treating disease, e.g. Danon disease.

The present invention relates to a composition for enhancing oncolytic virus activity which comprises nc886, and a composition for enhancing virus production which comprises the same.

Systems and methods are presented that allow for selection of tumor neoepitopes that are then used to generate recombinant nucleic acids that encode one or more polytopes that are optimized for proper trafficking and processing. In preferred methods, the polytopes are encoded in a plasmid and/or a viral expression system for use as a therapeutic agent.

The present invention refers to a sgRNA molecule comprising a targeting domain for specifically targeting a SNP in the BEST1 coding region of a pathologic allele, wherein said targeting domain consists of a sequence selected from the group consisting of SEQ ID NO: 3-8, 41-44, 14-20, 50-52 and 54-55, or a sgRNA molecule combination of specifically defined first and second sgRNA molecules, wherein the first and the second sgRNA molecule each comprise a targeting domain for specifically targeting a SNP in the BEST1 gene coding or non-coding region of a pathologic allele. The present invention also refers to a nucleic acid comprising a sequence that encodes the sgRNA molecule or sgRNA molecule combination and to nucleic acid combinations. The present invention further relates to a recombinant adenovirus-associated vims (AAV) comprising the nucleic acids according to the present invention or recombinant AAV combinations. The sgRNA molecule, the nucleic acid, the recombinant AAV and combinations are useful tools for editing of the target domain in the bestrophin-1 (BEST1) gene to restore BEST1 channel function by e.g. CRISPR/Cas9-based gene editing. The present invention further relates to the sgRNA molecule, the sgRNA molecule combination, the nucleic acid, the nucleic acid combination, the recombinant AAV and the recombinant AAV combination for use in a method for treatment of the human or animal body by surgery or therapy and for use in method of treating or preventing BEST1-related retinopathies, in particular autosomal dominant BEST1-related retinopathies.