The invention provides genetic constructs and recombinant vectors comprising such constructs. The constructs and vectors can be used in gene therapy methods for treating a range of disorders, including glaucoma and deafness, or for promoting nerve regeneration and/or survival.

The present invention relates to a nucleic acid coding for a human DGKk protein lacking a functional Proline Rich Region and/or a functional EPAPE repeated Region, and to its use in the treatment of fragile X syndrome in a patient in need thereof.

The present invention relates to a RNA encoding an antibody or a fragment or variant thereof and a composition, in particular a passive vaccine, comprising such an RNA. The present invention further relates to the use of such an RNA or of such a composition 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 also relates to a combination of at least two modified RNA's, in particular wherein one RNA encodes a heavy chain variable region of an antibody and another RNA encodes the corresponding light chain variable region of said antibody.

The present invention relates to a nucleic acid expression cassette, in particular for the expression of a human liver-specific and/or liver-expressed protein and/or preferably physiologically active domains and/or fragments thereof in a patient suffering from a monogenetic disorder caused by a mutation in the gene coding for the liver-specific and/or liver-expressed protein.

The present disclosure provides, among other aspects, codon-altered polynucleotides encoding Factor IX variants for expression in mammalian cells. In some embodiments, the disclosure also provides mammalian gene therapy vectors and methods for treating hemophilia B. In some embodiments, the present disclosure provides methods for dosing a hemophilia B patient with a polynucleotide, e.g., a codon-altered polynucleotide, encoding a Factor IX polypeptide.

Aspects of the disclosure relate to compositions and methods for exon replacement in a cell or a subject. In some embodiments, the disclosure relates to isolated nucleic acids (and vectors, such as rAAV vectors) encoding one or more guideRNAs (gRNAs) that target an intron-exon boundary; an intronic sequence having a splice signal; and a donor sequence encoding a gene product of a gene of interest, or portion thereof. In some embodiments, compositions described herein are useful for replacing mutant exons associated with certain diseases, for example Duchen's muscular dystrophy (DMD), cystic fibrosis (CF), spinal muscular atrophy (SMA), Rett syndrome, and mucopolysaccharidosis (MPS).

Described herein are engineered nucleases comprising mutations in the cleavage domain (e.g., FokI or homologue thereof) and/or DNA binding domain (zinc finger protein, TALE, single guide RNA) such that on-target specificity is increased.

The invention provides, in part, compositions and methods for treating neuronal ceroid lipofuscinoses (NCL). The invention further provides, in part, gene therapy compositions and methods for the treatment, prevention, or amelioration of at least one symptom of NCL. Particular embodiments provide a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a lentiviral vector, or a mammalian cell transduced with a lentiviral vector. Further embodiments provide a method of treating NCL comprising administering a lentiviral vector or a mammalian cell transduced with a lentiviral vector.

The disclosure relates to nucleic acid expression cassettes for the treatment of neurodegenerative disorders. Methods of treating neurodegenerative disorders such as Alzheimer's disease, frontotemporal dementia, frontotemporal lobar degeneration, Pick's disease, Lewy body dementia, memory loss, cognitive impairment, and mild cognitive impairment are also provided.

Disclosed herein are therapeutic agents capable of increasing the expression level of ELOVL2. Also described herein are therapeutic agents that reduce or slow an aging phenotype. Methods for treating age-related eye diseases or conditions are also provided. Methods for treating an age-related eye disease or condition in a subject by administering one or more therapeutic agents are provided.