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| 2021-05-06 07:26:22 | onclick： | Chinese scientists found a new gene pruning system is expected to boost RNA gene therapy |
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Yang Hui's team from the center for excellence and innovation in brain science and intelligent technology, Chinese Academy of Sciences (Institute of Neurology, Chinese Academy of Sciences) found two new CRISPR / cas13 systems through calculation and analysis of large-scale microbial metagenomic data, and developed a set of RNA editing tools with high efficiency and high specificity through a series of engineering transformation, This tool will play an important role in the development of gene therapy based on RNA editing. The results of the study were published in nature method online on May 3.
CRISPR / cas13 is a kind of RNA mediated targeted RNA cleavage system, which is widely used in RNA knockdown, RNA single base editing, and nucleic acid detection (such as new coronavirus detection). Compared with traditional RNA interference technology, cas13 system has higher knockdown efficiency and specificity; Moreover, compared with cas9 mediated DNA Editing Technology, cas13 does not cause permanent changes to the genome, and can even regulate RNA editing through drugs to make it reversible, so it has a unique advantage in disease treatment.
"The previously discovered cas13 systems are all mined from culturable microbial genomic data, but 90% of microorganisms in nature are unculturable. Therefore, our team's goal this time is to mine uncultured natural microbial metagenomic data. " Yang Hui told China Science Daily that this study identified two new cas13 families, named cas13x and cas13y, through ingenious computational biology algorithm and experimental design. Among them, cas13x. 1 protein is smaller than the commonly used rfxcas13d protein by nearly 200 amino acids, which is the smallest cas13 protein at present. Through RNA knockdown experiments on a large number of endogenous gene sites, cas13x. 1 showed the same high activity and specificity as rfxcas13d. After that, Yang Hui's team developed a mini RNA single base editing tool on the basis of cas13x. 1, and showed extremely low off target activity.
This work shows that cas13x. 1 has great potential in RNA editing, and is expected to become an efficient and safe RNA therapy drug in the future, providing more options for gene therapy of diseases (especially rare diseases)“ Finally, we have our own gene editing tools, and patents are no longer subject to human beings. ". It is understood that Yang Hui laboratory is currently testing the therapeutic effect of cas13x on more than 10 rare diseases and several common diseases, hoping that cas13x can be applied to the clinic as soon as possible to benefit patients.
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