Genetically modified non-human animals and methods and compositions for making and using the same are provided, wherein the genetic modification comprises a humanization of an endogenous signal-regulatory protein gene, in particular a humanization of a SIRPα gene. Genetically modified mice are described, including mice that express a human or humanized SIRPα protein from an endogenous SIRPα locus.

The present disclosure is directed, in some embodiments, to compositions and methods for inducible modification of a cell genome.

The present disclosure is directed, in some embodiments, to compositions and methods for inducible modification of a cell genome.

Provided is a method for preparing a PD-1 gene-modified humanized animal model. The method utilizes the CRIPSR/Cas9 technique to replace partial fragments of a mouse PD-1 gene with fragments of a human PD-1 gene using homologous recombination by constructing a targeting vector, thereby preparing a gene-modified humanized mouse. This mouse can normally express a PD-1 protein containing the functional domain of the human PD-1 protein, and can be used as an animal model for mechanism research regarding PD-1, PD-L1 and other signals, for screening regulators, and for toxicological research. The method has an important and high application value in studies on functions of the PD-1 gene and in the development of new drugs.

The present disclosure relates to the genetically modified non-human animals that express a human or chimeric (e.g., humanized) Lymphocyte Activation Gene 3 (LAG-3), and methods of use thereof.

The present disclosure relates to genetically modified non-human animals that express a human or chimeric (e.g., humanized) IL15, and methods of use thereof.

Chimeric transmembrane immunoreceptors (CAR) targeted to PSCA are described.

Genetically modified non-human animals and methods and compositions for making and using the same are provided, wherein the genetic modification comprises a humanization of an endogenous signal-regulatory protein gene, in particular a humanization of a SIRP gene. Genetically modified mice are described, including mice that express a human or humanized SIRP protein from an endogenous SIRP locus.

The invention provides an experimental research method for targeted therapy of prostate cancer by nuclide .sup.125I-labeled dual-regulation oncolytic adenovirus, comprising cloning and identification of prostate specific antigen PSA promoter; of adenoid construction and identification of hTERT/PSA double-regulated adenovirus vector RSOAds-hTERT/PSA; nuclide .sup.125I-labeled hTERT/PSA dual-regulation proliferative oncolytic adenovirus construction .sup.125I-RSOAds-hTERT/PSA nuclide-oncolytic virus marker; detection of transfection efficiency and tumor killing effect of .sup.125I-RSOAds-hTERT/PSA on hormone-independent prostate cancer cells in vitro; .sup.125I-RSOAds-hTERT/PSA targeted therapy for anti-tumor effect of prostate cancer and observation of tumor microenvironment changes. The invention can realize accurate impact analysis, and realizes the detection and analysis of the effect of the dual-regulated oncolytic adenovirus of the .sup.125I-labeled PSA/hTERT promoter on prostate cancer targeted therapy and tumor microenvironment through a comprehensive experimental method, and ensures the accuracy and reliability of the results.

Described herein are donor vectors and systems for use in in vivo dual recombinase-mediated cassette exchange. Also described are animal models for consistent, rigorous, and facile investigation of transgene expression. Further described are methods of screening for therapeutic drugs using these animal models, and methods of treatment