CRISPR相关转座元件的研究及应用进展

Recent advances in CRISPR-related transposable elements

摘要:

CRISPR-Cas的基因编辑能力引发了人们对该系统的研究热潮。除了实现基因的敲除和插入，CRISPR-Cas系统还可以被应用于基因簇重组、单碱基编辑和基因转录调控，推动了生物工程领域的发展。然而，有限的同源重组效率使CRISPR-Cas系统的应用受到了一定的限制。与CRISPR-Cas系统相比，移动遗传元件(mobile genetic elements,MGE)在转座酶的调控下，不需要依赖同源重组即可将指定DNA片段定向插入到细胞染色体中。近几年，人们发现了具有转座机制的CRISPR相关的转座元件，它可以介导DNA靶向整合，同时其出色的重编程能力为该领域的研究带来了新的发展。本文主要介绍近年来CRISPR-Cas系统相关转座元件的研究方向和应用进展，以及人工融合的dCas9-transposase系统的应用策略。文中还提出了CRISPR相关转座元件未来的应用前景和潜在挑战，为基因编辑工具的发展方向提供了参考意见。

Abstract:

A new wave of research has been inspired by the CRISPR-Cas system with respect to their application in genome editing. The CRISPR-Cas system can not only be applied in gene knockout and insertion, but also be used in base editing, transcriptional regulation and recombination of gene clusters. However, the low efficiency of homology-directed repair (HDR) limits its application. Unlike the CRISPR-Cas system, mobile genetic elements (MGE) can insert DNA fragments into cell chromosomes without the aid of HDR. Recently, it is reported that CRISPR-related transposable elements can guide targeted DNA insertion. Their transposition mechanisms and reprogramming abilities have brought novel opportunities to the development of this field. This review summarized the research progress and application development of natural CRISPR-related transposable elements in recent years, as well as the applications of fused dCas9-transposase. It proposed the application prospects and potential challenges of CRISPR-related transposable elements in the future, which provided a reference for the development direction of gene editing tools.