The present invention provides Factor IX fusion proteins with higher specific activity and a longer useful clotting function relative to wild type or non-modified Factor IX protein.

There is provided a vector for treating retinal degeneration associated with Bardet-Biedl Syndrome (BBS), wherein the vector comprises a promoter operably linked to a BBS1 gene, wherein the promoter is selected from a rhodopsin kinase (RK) promoter, a cytomegalovirus immediate-early (CMV) promoter and a CAG promoter, and wherein the vector is selected from an AAV2/8 vector, an AAV2/7m8 vector and an AAV9 vector. Also disclosed is a pharmaceutical composition comprising the vector, and use of the vector in a method of treating retinal degeneration associated with BBS comprising administering a therapeutically effective amount of the vector to a patient suffering from BBS, wherein the vector is administered directly to the eye of the patient.

The present invention provides Factor IX fusion proteins with higher specific activity and a longer useful clotting function relative to wild type or non-modified Factor IX protein.

Provided herein, in some aspects, are compositions and methods for treating Barth syndrome (BTHS) using human tafazzin gene therapy or enzyme replacement therapy. The present disclosure, in some aspects, provides compositions and methods (e.g., gene therapy or enzyme replacement therapy) for treating Barth syndrome (BTHS). It was demonstrated herein that certain human Tafazzin (hTAZ) isoforms and the full length protein, as well as nucleic acids encoding them, are effective in treating BTHS.

Provided are nucleotide sequences encoding polypeptides with ribonuclease III activity, wherein the nucleotide sequences have been modified to reduce their regulation by miRNAs. In some embodiments, the nucleotide sequences are at least 50% and as much as 100% identical to SEQ ID NO: 20 or SEQ ID NO: 22, and/or encode polypeptides that are at least 90% percent identical to SEQ ID NO: 23. Also provided are vectors and host cells that include the nucleotide sequences, methods for expressing the nucleotide sequences in cells, tissues, and organs, which in some embodiments can be in the eye of a subject in need thereof, methods for preventing and/or treating development of diseases or disorders and/or for restoring undesirably low DICER1 expression using the nucleotide sequences, and pharmaceutical compositions that have the presently disclosed nucleotide sequences.

The present invention features a dual vector system for disrupting and replacing a target gene comprising a mutation (e.g., dominant, recessive mutation). Embodiments of the invention may also provide compositions comprising the dual vector system, and methods of using the dual vector system, including but not limited to methods of modifying the genome of a cell, methods of genomic editing, and methods of treating cells or a subject suffering from a genetic disease comprising a mutation.

Non-human animal cells and non-human animals comprising CRISPR/Cas synergistic activation mediator system components and methods of making and using such non-human animal cells and non-human animals are provided. Methods are provided for using such non-human animals to increase expression of target genes in vivo and to assess CRISPR/Cas synergistic activation mediator systems for the ability to increase expression of target genes in vivo.

Some embodiments of the invention include modified cells. Certain embodiments of the invention include methods of using modified cells. Other embodiments of the invention include methods of administering modified cells. Further embodiments of the invention include methods of administering modified cells to treat diseases. Additional embodiments of the invention are also discussed herein.

The present invention concerns an expression system for systemic administration comprising a sequence encoding a FKRP protein, and: —a promoter sequence allowing the expression at a therapeutically acceptable level of FKRP in the skeletal muscles and a target sequence of an miRNA expressed in the heart; or—a promoter sequence allowing the expression at a therapeutically acceptable level of FKRP in the skeletal muscles and presenting a promoter activity at a toxically acceptable level in the heart; and its use for the treatment of various diseases linked to FKRP deficiencies.

Provided herein are polynucleotide constructs comprising a CD11b promoter operably linked to a nucleic acid encoding one or more therapeutic polypeptides, to vectors, cells, and/or compositions comprising the same, and to methods of their use.