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 provides non-human animal models of neuronal injury and/or cognitive dysfunction and methods of making and using such animal models. The animal models of the invention are particularly suited to assessing neurodegeneration in selected regions of interest in the CNS, and thus especially useful for testing the therapeutic efficacy of agents targeting neurodegeneration associated with aging, neurodegenerative diseases, autoimmunity and trauma (e.g., ischemia).

The present invention provides delivery methods and constructs for treating inflammatory diseases in an individual. The targeted delivery approach utilizes an antibody that recognizes an epitope found to be present at sites of inflammation. The antibody is used to deliver a MAp44 polypeptide or fragment thereof to sites of inflammation, where it inhibits the lectin pathway of complement activation.

The present invention relates to a method for treating and/or preventing a disease associated with protein aggregation which comprises the step of preventing protein aggregation associated with RNA removal, by stabilising RNA; or reversing protein aggregation associated with RNA removal, by effectively replacing removed RNA.

The present invention provides non-human animal models of neuronal injury and/or cognitive dysfunction and methods of making and using such animal models. The animal models of the invention are particularly suited to assessing neurodegeneration in selected regions of interest in the CNS, and thus especially useful for testing the therapeutic efficacy of agents targeting neurodegeneration associated with aging, neurodegenerative diseases, autoimmunity and trauma (e.g., ischemia).

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.

Methods, agents, and compositions for promoting milk production in a mammal are provided. Agents useful for promoting milk production may include an agent that inhibits NOTCH4 activity. The agent may inhibit NOTCH4 activity by binding to ROBO2 and/or by binding to NOTCH4. The agent may inhibit NOTCH4 by competing with ROBO1 for binding to ROBO2, thereby making ROBO1 available to inhibit NOTCH4 activity. The agent may be a soluble ROBO1 extracellular domain or an anti-NOTCH4 antibody that inhibits NOTCH4 activity. The agent may be an RNAi construct that inhibits expression of NOTCH4 or an RNAi construct that inhibits expression of ROBO2. Also provided herein are transgenic mammals genetically modified for expression of a soluble ROBO1 extracellular domain; inhibition of expression of ROBO2; and/or inhibition of expression of NOTCH4. Methods for promoting milk production in such transgenic mammals by administering one or more of the agents disclosed herein are also provided.

This invention is directed to methods for manipulating sex, reversing sex, changing sex ratio, or moderating crustacean androgenic gland peptide expression in crustaceans for producing a monosex culture. In one embodiment, the present method comprises the step of injecting a dsRNA for the gene of IAG into a male crustacean. In another embodiment, the present method comprises the step of injecting a dsRNA for the gene of IAG into a female crustacean that had acquired a spermatophore (a sperm sac) after mating with a male. In another embodiment, the present invention provides a method of producing a monosex culture of crustacean by introducing a recombinant IAG peptide into the female crustacean, thereby obtains male with altered sexual characteristics for mating with a normal female. In one embodiment, the crustacean is a shrimp or lobster.

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.

Monoclonal antibodies exhibiting an VH4 signature associated with multiple sclerosis (MS) and clinically isolated syndrome have been produced and sequenced. These antibodies antibodies recognize neuronal nuclei and/or astrocytes in both mouse and human gray matter (GM) brain tissue and thus are useful in binding assays for such. They are also useful in the production of MS animal models, and as targets for MS therapies.