This application relates to therapeutic siRNA agents and methods of making and using the agents.

The present invention relates to a method for screening an anticancer agent by causing drosophila having the characteristics of a) expression of mutant Ras85D, b) deletion or suppressed expression of a p53 gene, c) overexpression of a cyclin E gene, and d) deletion or suppressed expression of a Med gene to ingest a test substance and comparing the survival rate thereof with the survival rate of drosophila that did not ingest the test substance. The present invention also relates to a combination drug of at least two kinase inhibitors for treatment of pancreatic cancer and to kinase inhibitors for use in said combination drug.

Provided is a method for preparing a diabetic dog model by means of gene editing technology, a diabetic dog model prepared therefrom, as well as cells and issues thereof. The method comprises the following steps: (1) obtaining a dog fertilized egg cell, which comprises a point mutation in GCK gene, for a diabetic dog model by means of gene editing; and (2) transplanting the dog fertilized egg cell into one fallopian tube of a female dog, in which both fallopian tubes have been flushed, to prepare a diabetic dog model comprising a point mutation in GCK gene.

The present disclosure provides a pharmaceutical composition for treating Alzheimer's disease and use thereof, the pharmaceutical composition containing, as an active ingredient, stem cells (SC) having high adaptability under hypoxic conditions. Particularly, the present disclosure discloses a pharmaceutical composition for alleviating or treating the symptoms of Alzheimer's disease, the pharmaceutical composition containing, as an active ingredient, mesenchymal stem cells (MSC) which have high adaptability or viability in hypoxic environments and comprise one or more knock-out HIF1AN genes.

Provided are a fusion protein that improves gene editing efficiency and an application thereof. The fusion protein comprises a single-stranded DNA binding protein functional domain, nucleoside deaminase and nuclease. According to CBEs, when carrying our base conversion from C-G to T-A, nucleoside deaminase such as cytosine deaminase carries out deamination by using single-stranded DNA as a substrate, and by re-fusing the single-stranded DNA binding protein functional domain on the fusion protein of the nucleoside deaminase and nuclease, the chance of single-stranded DNA being exposed to the nucleoside deaminase is greatly increased, thereby significantly improving base editing efficiency. The present disclosure provides a breakthrough improvement of single-base gene editing technology and can greatly promote the application thereof in aspects such as gene editing, gene therapy, cell therapy, animal model making, and crop genetic breeding.

A preparation method of an anti-PD-1/PD-L1 monoclonal antibody (mAb)-induced autoimmune myocarditis model is provided, including: mediating a model with adeno-associated virus 9 (AAV9) to achieve the high expression of PDL1 in a myocardial tissue, and applying an anti-PD-1/PD-L1 mAb to the model with high PDL1 expression in the myocardial tissue for modeling. The present disclosure also provides use of an animal model prepared by the preparation method. The model prepared by the present disclosure truly simulates the pathogenesis and clinical course of autoimmune myocarditis in a patient administered with an anti-PD1/PD-L1 mAb, is close to a pathophysiological status of a clinical patient, has a high modeling rate, and can be dynamically monitored.

Provided is an invention that is based on the novel function of a transcription factor RP58 in cells of the central nervous system. The present invention relates to: a transgenic non-human animal capable of increasing or decreasing the expression of the transcription factor RP58 in cells of the central nervous system of a non-human animal in the nascent stage and/or during and after the developmental stage; and a pharmaceutical composition for use in the treatment or prevention of brain dysfunction, or behavioral disorder, or a disease related thereto, wherein the pharmaceutical composition comprises a transcription factor RP58 protein, or a gene encoding the transcription factor RP58; etc.

An engineered genetic incompatibility (EGI) strain of a wild-type organism is designed to include a haplosufficient lethal allele and a haploinsufficient resistance allele. In another aspect, a biocontainment system generally includes a polynucleotide that encodes a coding region whose expression causes infertility or death, a transcription regulatory region operably linked upstream of the coding region and containing a silent mutation, and a polynucleotide that encodes a programmable transcription activator. The programmable transcription activator is engineered to bind to the transcription regulatory region in the absence of the silent mutation, thereby expressing the coding region in the absence of the silent mutation, but does not initiate expression of the coding region when the transcription regulatory region comprises the silent mutation.

The present invention provides a method of lowering blood pressure in a subject, comprising genetically modifying a myosin phosphatase target subunit (Mypt1) gene in a vascular smooth muscle cell of the subject, whereby the genetic modification of Mypt1 results in a deletion or inactivation of exon 24. The invention further provides vectors, host cells, and compositions useful for carrying out the methods of the invention.

A transgenic non-human animal is provided. In certain embodiments, the animal comprises a genome comprising an immunoglobulin heavy chain locus comprising: a) a transcribed gene encoding a fusion protein comprising, from N-terminus to C-terminus: i. a scaffold comprising a first binding domain; and ii. a heavy chain constant region operably linked to the scaffold; wherein the scaffold is capable of specifically binding to a target in the absence of additional polypeptides; and b) a plurality of pseudogenes that are operably linked to the transcribed gene and that donate, by gene conversion, nucleotide sequence to the part of the transcribed gene that encodes the binding domain.