Method for injecting virus into specific brain region of animal for gene editing based on non-treatment purpose of PSEN1 gene

Abstract

The invention discloses a method for injecting virus into a specific brain region of an animal for gene editing based on the non-treatment purpose of a PSEN1 gene. The method comprises the step of directly injecting virus into the specific brain region of a non-human primate by using a brain stereotactic injection pump, wherein the injection amount is 1 microliter of virus per 1m<3>, and the titerof the injected virus is 10*10<13> vg / mL. According to the method, virus is directly injected into the specific brain region of the non-human primate for gene editing, so that a transgenic monkey model with a disease phenotype can be obtained in a short time, and urgent research requirements of Alzheimer's disease (AD) at the present stage are met.

Description

technical field [0001] The invention belongs to the field of transgenic technology and modeling of non-human primates, and specifically relates to a non-therapeutic method based on the PSEN1 (PS1) gene for injecting viruses into specific brain regions of non-human primates for gene editing. Thus, a non-human primate AD disease model was constructed. Background technique [0002] Alzheimer's disease (AD) is a group of primary degenerative brain degenerative diseases of unknown etiology. The pathological changes are mainly diffuse atrophy of the cortex, widening of the sulci, enlarged ventricles, a large number of neurons, and senile plaques (senile plaques), neurofibrillary tangles and other lesions can be seen, accompanied by a significant decrease in the content of choline acetylase and acetylcholine . The onset is mostly in old age, the onset is insidious, the course of the disease is slow and irreversible, and the early manifestation is memory impairment. As the course ...

AI Technical Summary

Problems solved by technology

Although these models may have some characteristic pathological changes, none of them can simulate the progressive degenerative changes of human AD disease, so they are gradually eliminated by animal models constructed by transgenic technology

At present, there are only a few transgenic macaque models for macaque embryos, but (1) the genetic background of macaques varies greatly among individuals, and the problem of mosaicism in embryo transgenic technology cannot be solved, so these macaques based on embryo transgenes are still difficult to help. Let's observe and study the etiology and pathogenesis of AD

(2) The natural sexual maturity time of macaques is 5-6 years, and the gestation period takes 6 months. They are singleton animals. Therefore, it is difficult to achieve genetically manipulated monkeys that are homozygous by mating transgenic macaques at this stage.

(3) Transgenic monkeys based on embryo transgenic technology have high mortality rate, low success rate, poor stability of transgenic gene retention, and extremely long onset time. At present, it is difficult to establish a stable transgenic monkey model

Even if it is successfully established, it is difficult for this monkey model to reproduce in large numbers and the maintenance cost is extremely high, so it is difficult to meet the urgent research needs at this stage

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