Disclosed herein are rodents (such as mice and rats) genetically modified at an endogenous Scn9a locus to comprise an exogenous Scn nucleotide sequence such as the coding sequence of a human SCN2A gene. Also disclosed are methods and compositions useful for making such rodents, and methods of using such rodents for generating anti-NaV1.7 antibodies.

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.

The present disclosure is directed to compositions and methods for the treatment of Metabolic Liver Disorders. The compositions and methods can comprise an adeno-associated virus (AAV) piggyBac polynucleotide comprising a transgene. The transgene may comprise ornithine transcarbamylase (OTC) or methylmalonyl-CoA mutase (MUT1).

The present disclosure provides a method of generating a T cell comprising a transgene integrated at a first site within the genome of the T cell, wherein the transgene encodes a polypeptide that is a subunit of a negative elongation factor (NELF) complex. The T cells can be administered to treat cancer and infectious disease.

One variation of a method includes: during an initial period, modifying a population of insects to produce a target compound responsive to application of a stressor; during a growth period succeeding the initial period, cultivating the population of insects according to a set of growth conditions; and, during a treatment period succeeding the growth period, applying a dosage of the stressor to the population of insects to trigger production of the target compound. The method further includes, during a harvest period succeeding the treatment period: harvesting the population of insects; homogenizing the population of insects to form a blend including a set of secondary components and an amount of the target compound; extracting the amount of the target compound from the blend; and mixing the first amount of the first target compound with a set of stabilizing agents configured to stabilize the target compound.

The invention discloses a method for screening a therapeutic target of acute radiation-induced gastrointestinal syndrome and use of TIGAR target in the preparation of a medicine for treating radiation-induced gastrointestinal syndrome. The CreERT-loxP transgenic mouse model is used, in which quiescent intestinal crypt stem cells are effectively promoted to proliferate after exposure to high-dose ionizing radiation, to screen a therapeutic target that still has a therapeutic effect for radiation-induced gastrointestinal syndrome 18-24 h after ionizing radiation. Gene splicing occurs in particular cells in the CreERT-loxP transgenic mice only after the injection of tamoxifen, thereby regulating gene expression. The actual situation of initial exposure and then treatment after a nuclear accident is well simulated, so the invention is of great practical significance. The screened therapeutic target is developed into a medicine for treatment after nuclear accidents, to save precious time for the treatment after nuclear accidents.

The present disclosure relates to nucleic acid promoter sequences that are able to specifically express genes operatively linked to the promoter in brainstem and spinal motor neuron cells, and to methods for using such promoters to selectively express genes in motor neurons in vitro and in vivo. It is based, at least in part, on the discovery that the nucleic acid of SEQ ID NO: 1 functioned as a motor neuron-specific promoter and was successful in expressing transgenes in motor neuron cells in vivo. The present disclosure also relates to compositions that can increase the activity or expression level of miR-218 and to compositions that can decrease the expression of miR-218 target nucleic acids.

The invention relates to nucleic acid constructs for expression in mice for the reproduction of heavy chain only antibodies and V.sub.H domains, transgenic mice, related methods and uses.

Provided is a modified double-stranded oligonucleotide, in which the sense strand comprises a nucleotide sequence 1, the anti-sense strand comprises a nucleotide sequence 2, the nucleotide sequences 1 and 2 are both 19 nucleotides in length, and in the direction from 5′ end to 3′ end, nucleotides at positions 7, 8 and 9 of the nucleotide sequence 1 and nucleotides at positions 2, 6, 14 and 16 of the nucleotide sequence 2 are all fluoro-modified nucleotides, and each nucleotide at other positions is independently one of non-fluoro-modified nucleotides. Further provided are a pharmaceutical composition and a conjugate comprising the oligonucleotide, and pharmaceutical use thereof.

Provided herein are compositions and methods for selective expression of a transgene. Compositions and methods for selective expression of a transgene comprise one or more human regulatory elements, which, when operably linked to a transgene, can facilitate selective expression of a transgene (for example, cell-type selective expression) in a target cell as compared to at least one or more non-target cells.