Complexes comprising a nucleic acid-guided endonuclease, a sequence-specific targeting nucleic acid and an amphipathic helical peptide are provided. Compositions and methods for delivery of complexes comprising a nucleic acid-guided endonuclease, a sequence-specific targeting nucleic acid and an amphipathic helical peptide to mammals for both research and therapeutic use are provided. Methods of treating or reducing one or more symptoms of type 2 diabetes, prediabetes and/or gestational diabetes are provided.

Methods of generating functional human organs and tissue in animal bodies suitable for transplantation into human subjects are provided. In particular, the contribution of human donor cells to tissues and organs can be increased in interspecies host embryos by knocking out a growth factor receptor gene such as the insulin-like growth factor 1 receptor or insulin receptor gene. Almost entirely donor-derived functional organs and tissue can be generated by using this method. The methods described herein are useful for generating human organs and tissue in animals and may be helpful for overcoming the current problems with organ shortage for transplantation therapy. Additionally, such organs and tissue can be used in drug discovery, drug screening, and toxicology testing.

Provided is an antibody or an antigen-binding fragment thereof, a T cell antigen receptor, an immune cell expressing the T cell antigen receptor (TCR), and a preparation method therefor and the use thereof. The TCR can specifically recognize corresponding pMHC complexes, activate TCR T cells, and produce high-level cytokines IFNγ, IL2, TNFα, significantly kill target cells and prolong the life of tumor-bearing mice.

The present disclosure is directed to novel methods of treating type-1 or type-2 diabetes by inactivating TLR2 and TLR4 genes together in cells capable of producing insulin and/or regenerating β cells, and providing the cells to a subject in need thereof.

The present application relates to a non-human mammal model of a human neurodegenerative disorder, methods of producing the non-human mammal model, and methods of using the non-human mammal model to identify agents suitable for treating a neurodegenerative disorder. The present application also relates to methods of treating neurodegenerative disorders and restoring normal brain interstitial potassium levels.

Disclosed herein are rodents (such as, but not limited to, mice and rats) genetically modified to comprise a humanized Cxcl13 gene. The rodents disclosed herein have been shown to support better engraftment and proliferation of human cells such as chronic lymphocytic leukemic cells. Compositions and methods for making such genetically modified rodents, as well as methods of using such genetically modified rodents for testing candidate therapeutic agents (e.g., candidate anti-cancer drugs), are provided.

There is provided method for making a cell composition which comprises step of transducing a population of cells with a mixture of at least two viral vectors, wherein at least one vector comprises a nucleic acid sequence which encodes a chimeric antigen receptor (CAR); and wherein at least one vector comprises a nucleic acid encoding an activity modulator which modulates the activity of the CAR, of a cell expressing the CAR, or of a target cell. There is also provided a cell composition made by such a method and its use in the treatment of diseases such as cancer.

Methods and compositions are provided for making non-human animals with reduced tolerance of a foreign antigen of interest and making antigen-binding proteins against that foreign antigen of interest using such animals. The methods and compositions employ CRISPR/Cas9 systems using multiple guide RNAs to reduce or eliminate expression of a self-antigen homologous to or sharing an epitope of interest with the foreign antigen of interest or to reduce or eliminate expression of an epitope on the self-antigen that is shared with the foreign antigen of interest.

The invention relates generally to genetically modified non-human animals expressing human polypeptides and their methods of use.

Bispecific aptamers having a first end that specifically binds to a first tumor specific marker, tumor antigen, or viral protein and a second end that specifically binds to a second tumor specific marker, tumor antigen, or viral protein are provide. The bispecific aptamers can be used to treat cancer or virally infected cells. Generally, the bispecific aptamers bind to two surface proteins, preferably different proteins, on the same cell. In a preferred embodiment the bispecific aptamers bind to two different tumor markers, tumor antigens, tumor specific proteins and combinations thereof.