Nonsense-mediated mRNA decay (NMD) polypeptides, nucleic acids encoding NMD polypeptides, and methods of using such polypeptides and nucleic acids in the treatment of ALS and in screening for agents for the treatment of ALS are described.

Provided here are certain recombinant HIV compositions and animal models to evaluate prophylactic and therapeutic antiviral compositions.

Described herein are methods and compositions for autocatalytic genome editing and neutralizing autocatalytic genome editing. The autocatalytic genome editing may be based on genomic integration of a construct containing multiple elements or on a trans-complementation approach, in which genetic elements can be propagated separately. The disclosure provides a method for autocatalytic genome editing based on the CRISPR/CAS9 system, and methods of use thereof, in animals, humans, and plants for eliminating pathogens, targeting suppression of crop pests, strategies to combat virus (e.g., HIV) and other diseases (e.g., cancer) caused by retrovirus, as well as to generate homozygous mutations that are transmitted to nearly all offspring.

Nonsense-mediated mRNA decay (NMD) polypeptides, nucleic acids encoding NMD polypeptides, and methods of using such polypeptides and nucleic acids in the treatment of ALS and in screening for agents for the treatment of ALS are described.

The invention is directed to a method of producing a non-human mammal having one or more pathological characteristics of retinal degeneration and/or age-related macular degeneration. In particular, the invention provides a method of producing a non-human mammal having age-related macular degeneration (AMD). The invention is also directed to non-human animals produced by the methods described herein. Methods of identifying an agent for use in inhibiting one or more pathological characteristics of retinal degeneration and/or AMD is also encompassed by the invention. Also provided is a method of treating AMD in an individual in need thereof comprising, administering to the individual an agent identified herein.

The present invention provides a disease model animal for tauopathies which reproduces the expression pattern of tau protein isoforms of adult human brain, that is, approximately equal amounts of 3R type tau and 4R type tau being expressed in the adult brain. The method for producing the disease model animal for tauopathies of the present invention comprises the steps of: preparing a tau seeds; and injecting the tau seeds in the brain of an animal carrying a mutation in the tau gene which fails to express the tenth exon. The animal carrying a mutation in the tau gene which fails to express the tenth exon may be produced by using any of the genome editing, gene targeting or base editing technologies.

The present invention provides methods of making an in vivo animal model for detecting anti-poly(ethylene glycol) (PEG) antibodies. The methods of the disclosure comprises administering subcutaneously to an animal model a composition comprising antibodies against poly(ethylene glycol) chains with a molecular weight of at least 550 Da to maintain an anti-PEG antibody level within the animal model. The in vivo animal model can be used for testing and screening drugs and other compositions for adverse reactions, bioavailability, and immunogenicity prior to administration to a human subject.

This disclosure describes exemplary embodiments of a method of creating a YY animal broodstock, preferably in a single generation, wherein the broodstock includes only sperm-producing YY males and egg-producing YY males, the method comprising the steps of: (a) creating YY males via androgenesis; (b) exposing selected ones of the YY males created in step (a) to a feminizing hormone; and (c) identifying sperm-producing YY males and egg-producing YY males from among the YY males created in steps (a) and (b). In other embodiments, the method further comprises: (d) repeating steps (a) through (c) N times in order to produce N unrelated families of sperm-producing YY males and egg-producing YY males; and (e) cross-breeding various ones of the unrelated families produced in step (d) in order to produce a genetically-diverse YY progeny. In some embodiments, N may be about 60.

A method of modulating some or all copies of a gene in a cell is provided including introducing into a cell one or more ribonucleic acid (RNA) sequences that comprise a portion that is complementary to all or a portion of each of the one or more target nucleic acid sequences, and a nucleic acid sequence that encodes a Cas protein and maintaining the cells under conditions in which the Cas protein is expressed and the Cas protein binds and modulates the one or more target nucleic acid sequences in the cell.

The present invention relates to a composition comprising a peptide derived from myelin basic protein (MBP) peptide for use in treating or preventing uveitis in a subject