Disclosed herein are recombinant meganucleases engineered to recognize and cleave a recognition sequence present in the human mitochondrial DNA (mtDNA). The disclosure further relates to the use of such recombinant meganucleases in methods for producing genetically-modified eukaryotic cells, and to a population of genetically-modified eukaryotic cells wherein the mtDNA has been having modified or edited.

The present invention provides a new animal model for mucopolysaccharidosis type lVA or Morquio A syndrome and to methods of generating the animal model and uses thereof.

The present invention relates to hybrid transcription regulatory elements to drive gene expression, in particular hybrid promoters, designed by the fusion of at least two transcription regulatory elements with different tissue selectivity, such as two promoters driving expression in different tissues in a tissue-selective manner.

The present invention is directed to gene therapy constructs and pharmaceutical compositions for the expression of Kir7.1. The gene therapy constructs include a vector comprising a promoter operably connected to a polynucleotide encoding a Kir7.1 polypeptide. Methods of treating a subject having a condition associated with insufficient expression or function of a Kir7.1 polypeptide are also provided.

Provided is a gene therapy vector for treating a retinitis pigmentosa disease. A targeted specific optimization design is performed on a PROM1 gene coding sequence so as to obtain a nucleotide sequence particularly suitable for efficiently expressing a PROM1 protein in a mammalian (such as human) cell (in particular, a photoreceptor cell), and a recombinant AAV virus for expressing a normal human PROM1 protein is constructed. Compared with a coding sequence which is not optimized, the expression level of the PROM1 coding sequence (SEQ ID NO.:1) performed specific optimization is increased as more than three times. The sequence is particularly suitable for expressing a mammalian (such as human) cell. Eye diseases such as a retinitis pigmentosa disease can be treated efficiently.

A gene therapy vector is used in the treatment of progressive familial intrahepatic cholestasis type 2. More specifically, an adeno-associated virus vector includes codon-optimized sequence encoding for the BSEP for the treatment of PFIC2.

The present invention relates to a method of integrating an exogenous DNA sequence into a genome of a cell comprising contacting the cell with: a) a donor nucleic acid comprising: —at least one STOP codon and a translation initiation sequence (TIS) or —a ribosomal skipping sequence, and —said exogenous DNA sequence wherein said donor nucleic acid is flanked at 5′ and 3′ by inverted targeting sequences; b) a complementary strand oligonucleotide homologous to the targeting sequence and c) a nuclease that recognizes the targeting sequence.

Disclosed herein are compositions and methods of treating disclosure provides for compounds for use in treating Mitochondrial Neurogastrointestinal Encephalopathy Syndrome (MNGIE). In some embodiments, the compounds have cell penetrating activity and thymidine phosphorylase activity. In certain embodiments, the compounds disclosed herein comprise: a) at least one cell-penetrating peptide (CPP) moiety; and b) a thymidine phosphorylase, or an active fragment or analog thereof (TP), wherein the CPP is coupled, directly or indirectly, to TP.

Compositions for improved gene editing and methods of use thereof are disclosed. In a preferred method, gene editing involves use of a cell-penetrating anti-DNA antibody, such as 3E10, as a potentiating agent to enhance gene editing by nucleases and triplex forming oligonucleotides. Genomic modification occurs at a higher frequency when cells are contacted with the potentiating agent and nuclease or triplex forming oligonucleotide, as compared to the absence of the potentiating agent. The methods are suitable for both ex vivo and in vivo approaches to gene editing and are useful for treating a subject with a genetic disease or disorder. Nanoparticle compositions for intracellular delivery of the gene editing compositions are provided and are particularly advantageous for use with in vivo applications.

Compositions for enhanced gene editing and methods of use thereof are. The composition contains a cell-penetrating antibody and a donor oligonucleotide containing a sequence that can correct a mutation in a cell's genome. Preferably, the composition does not contain a nuclease, PNA, or nanoparticle. The compositions are used to modify the genome of a cell by contacting the cell with an effective amount of the composition. Genomic modification occurs at a higher frequency both ex vivo and in vivo, when cells are contacted with the cell-penetrating antibody and donor oligonucleotide as compared to the absence of the cell-penetrating antibody.