This invention relates to the engineering of animal cells, preferably mammalian, more preferably rat, that are deficient due to the disruption of tumor suppressor gene(s) or gene product(s). In another aspect, the invention relates to genetically modified rats, as well as the descendants and ancestors of such animals, which are animal models of human cancer and methods of their use.

Methods and compositions are provided herein for assessing CRISPR/Cas-mediated non-homologous end joining (NHEJ) activity and/or CRISPR/Cas-induced recombination of a target genomic locus with an exogenous donor nucleic acid in vivo and ex vivo. The methods and compositions employ cells and non-human animals comprising a Cas expression cassette such as a genomically integrated Cas expression cassette so that the Cas protein can be constitutively available or available in a tissue-specific or temporal-specific manner. Methods and compositions are also provided for making and using these non-human animals, including use of these non-human animals to assess CRISPR/Cas activity in vivo via adeno-associated virus (AAV)-mediated delivery of guide RNAs to the non-human animals.

Provided are compounds that target the lanthionine synthetase C-like protein 2 pathway and cells, such as immune cells, prepared in vitro with the compounds. The compounds and cells can be used to treat a number of conditions, including infectious diseases, hyperproliferative disorders, inborn errors of metabolism, chronic immunometabolic diseases, autoimmune diseases, organ transplant rejection, inflammatory disorders, and chronic pain, among others.

Nucleic acid molecules and compositions, and methods using the same are provided herein for intraocular gene-based delivery and expression of two or more proneural bHLH transcription factors in the retina. The nucleic acid molecules, compositions and methods disclosed herein stimulate regeneration of retinal interneurons from retinal Müller glia (MG) and reprogram the MG into bipolar, amacrine, horizontal, and/or ganglion cells. Such methods and nucleic acid molecules are used for vision restoration and/or treatment of a range of ocular diseases involving retinal degeneration after injury, disease, or vison loss.

Truncated junctophilin-2 related proteins, transcriptional repressor domains, vectors encoding the proteins or domains, and methods of using the proteins and domains, are provided.

This invention relates to the engineering of animal cells, preferably mammalian, more preferably rat, that are deficient due to the disruption of tumor suppressor gene(s) or gene product(s). In another aspect, the invention relates to genetically modified rats, as well as the descendants and ancestors of such animals, which are animal models of human cancer and methods of their use.

The invention provides for transgenic donor animals (e.g., pigs) whose cells, tissues and organs have a better long-term survival when transplanted into a human patient. The transgenic donor animal carries one or more human transgenes which is expressed only when the endogenous gene of the donor animal is knocked out shortly before a graft is harvested for transplantation. This “genetic switch” allows the donor animal to remain healthy during the majority of its lifetime, while still allowing expression of the human transgene for optimal transplant tolerance in a human recipient. The transgene may encode a cytokine receptor, an adhesion molecule, or a complement regulatory protein.

Methods and compositions are provided for generating antigen-binding proteins against a foreign antigen of interest.

An all male Culicide mosquito population is created by knocking down its Transformer-2 gene, causing the dysfunction of X chromosome-bearing sperm, hence producing severe biased male progenies. Unlike previous methods, we recently discovered that the Tra-2 knockdown also results in female-specific zygotes lethality (XX). This art is therefore also designed to kill early female zygotes (XX) that may have survived the previous knockdown, and the all male progenies are created only when an antibiotic substance has been added into food and drink to feed mosquitoes. The strict limit of the antibiotic exposure time allows mosquito-adapted Wolbachia bacteria to survive. Selected Wolbachia bacteria may induce cytoplasmic incompatibility (CI) of up to 100%. All the progenies are therefore genetically males, which cause sterility when outcrossing with females infected by another Wolbachia strain (bidirectional CI) or are uninfected (unidirectional CI) in natural environment.

A method of producing a non-erythroid protein in erythrocytes of a transgenic animal using an erythroid-specific promoter includes synthesizing an erythroid-specific globin gene promoter and globin gene locus control region and cloning the promoter and the globin gene locus control region and a gene encoding a non-erythroid protein into a vector to obtain a transgene; introducing the transgene in pronuclear embryos collected from a mammalian animal in vitro; transplanting the pronuclear embryos containing the transgene into oviduct of a female recipient of the mammalian animal to obtain a transgenic animal which then expresses the non-erythroid protein in progenitor cells of erythrocytes; and collecting blood from the transgenic animal and isolating the non-erythroid protein from the erythrocytes. Further disclosed are a transgenic animal expressing a non-erythroid protein in progenitor cells of erythrocytes and an isolated erythrocyte of a non-human transgenic animal containing a human non-erythroid protein encoded by a transgene.