Compositions and methods for improving embryo development, treating idiopathic male factor infertility, and enabling infertile/sub-fertile/sterile men to father their own genetic offspring are provided. Typically, the methods include administering into a male or female gamete or fertilized embryo an effective amount of a compound that increases bioavailability of a TET protein to improve development of an embryo resulting from fertilization of the female gamete by a male gamete. The compound can be administered into the gamete or embryo before, during, or after fertilization. The compound can be administered by an injection such as intracytoplasmic injection. The compound and the male gamete can be administered in combination by intracytoplasmic sperm injection. Methods of making male gametes, and methods of modifying the genome of a male gamete or embryo using an effective amount of a gene editing composition to correct a gene mutation or anomaly in the genome thereof are also provided.

Provided herein are compositions for treating or preventing Retinitis Pigmentosa. The compositions comprise a first polynucleotide and a second polynucleotide. The compositions may further comprise a third sequence and a fourth sequence. Also provided herein are the recombinant adeno-associated virus particles, systems, methods, and kits for practicing or using the same.

This disclosure pertains to methods and compositions for tolerizing a mammal's brain to exogenously administered acid sphingomyelinase polypeptide by first delivering an effective amount of a transgene encoding the polypeptide to the mammal's hepatic tissue and then administering an effective amount of the transgene to the mammal's central nervous system (CNS).

The present invention relates to a method for producing animal models of cerebrovascular disease, comprising ligation of the common carotid artery (CCA) and administration of a nitric oxide (NO) inhibitor, animal models of cerebrovascular disease produced thereby, and a method for producing animals having small individual differences in susceptibility to the onset of cerebrovascular disease by using the same. The method for producing animal models of cerebrovascular disease according to the present invention can overcome the conventional problems of complexity and low yield. Particularly, the production method of the present invention can produce animal models of cerebrovascular disease with a high yield by a simple method. Moreover, the animal models produced by the production method may be used in studies to verify the effectiveness and safety of substances for the diagnosis, prevention or treatment of cerebrovascular disease or methods for treatment of cerebrovascular disease, and make it possible to study genes that cause differences in the level of cerebrovascular disease between the animal models. In addition, it is possible to provide offspring animals having uniform susceptibility to the onset of cerebrovascular disease by mating the animal models having similar susceptibilities to the onset of cerebrovascular disease according to the present invention.

The disclosure relates, in some aspects, to compositions and methods for treatment of diseases associated with aberrant lysosomal function, for example Parkinson's disease (PD) and Gaucher disease. In some embodiments, the disclosure provides expression constructs comprising a transgene encoding beta-Glucocerebrosidase (GBA) or a portion thereof alone or in combination with one or more PD-associated genes. In some embodiments, the disclosure provides methods of Parkinson's disease by administering such expression constructs to a subject in need thereof.

Provided herein is a recombinant AAV (rAAV) comprising an AAV capsid and a vector genome packaged therein, wherein the vector genome comprises an AAV 5′ inverted terminal repeat (ITR), an engineered nucleic acid sequence encoding a functional hSGSH, a regulatory sequence which direct expression of hSGSH in a target cell, and an AAV 3′ ITR. Also provided is a pharmaceutical composition comprising a rAAV as described herein in a formulation buffer, and a method of treating a human subject diagnosed with MPS IIIA.

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.

Disclosed are non-naturally occurring zebrafish, such as transgenic zebrafish, which comprise a mutation in the rhodopsin (rho) gene. Also disclosed are methods of identifying compounds useful in treating retinal-specific defects and disorders, such as degeneration. Further disclosed are methods of identifying mutations in the rhodopsin gene that can cause retinal-specific defects.

Recombinant polynucleotides encoding fragments of a human dysferlin protein are described herein. In addition, plasmids, viral vectors, dual vector systems, cells, and compositions comprising such recombinant polynucleotides are further described. Such recombinant polynucleotides, plasmids, viral vectors, dual vector systems, cells, and compositions may be used to treat dysfer-linopathies.

The present disclosure encompasses engineered meganucleases that bind and cleave recognition sequences within a dystrophin gene. The present disclosure also encompasses methods of using such engineered meganucleases to make genetically modified cells. Further, the disclosure encompasses pharmaceutical compositions comprising engineered meganuclease proteins, or polynucleotides encoding engineered meganucleases of the disclosure, and the use of such compositions for the modification of a dystrophin gene in a subject, or for treatment of Duchenne Muscular Dystrophy.