《生命科学》 2026, 38(10): 1697-1708
噬菌体逃逸CRISPR/Cas切割的机制研究进展
摘 要：
噬菌体在医学、食品、农业等领域具有广泛的应用，将CRISPR/Cas 基因编辑工具应用于噬菌体可加快其改造和深入研究。然而，噬菌体可以逃逸CRISPR/Cas 的切割，进而降低基因编辑效率。本文系统梳理目前的研究进展，归纳噬菌体逃逸CRISPR/Cas切割的4 类机制，包括编码抗CRISPR蛋白、修饰自身DNA、靶序列发生点突变或片段缺失、形成类核结构，旨在为噬菌体高效基因编辑工具的开发与实际应用提供理论参考。
通讯作者：李琦 , Email:liqi@sicnu.edu.cn
Abstract:
Phages have a wide range of applications in medicine, food, agriculture and other fields. In medicine, phages, as the core carrier of phage therapy, can be employed to combat multidrug-resistant bacterial infections; in the food industry, they can be used as natural biological preservatives to inhibit pathogenic bacterial contamination; in agricultural production, they can target and control crop pathogens, thereby improving crop yield and quality. Applying CRISPR/Cas gene editing tools to phage research can accelerate their genome modification and functional mechanism analysis, and provide technical references for the future development and application of phages. However, phages can escape the cleavage of the CRISPR/Cas system through multiple pathways, thus reducing gene editing efficiency. This phenomenon has become a key bottleneck
restricting the industrial application of the technology. This review aims to systematically summarize the research progress and current status of mechanisms underlying phage escape from CRISPR/Cas-mediated cleavage, and provide theoretical guidance for subsequent research. Firstly， this review elaborates on the important application value of phages in medicine, food, and agriculture. Secondly， it summarizes the immune function and gene editing principle of the CRISPR/Cas system, and clarifies the negative impact of phage escape on gene editing efficiency. Finally, based on recent domestic and international studies, four core escape mechanisms are summarized: the first is the encoding of anti-CRISPR (Acr) proteins, which interfere with Cas protein activity through competitive binding, complex dissociation or direct inactivation, thereby
evading cleavage; the second is the modification of their own DNA, which alters target site structures to prevent recognition and cleavage by the CRISPR/Cas system; the third is the occurrence of point mutations or fragment deletions in the target DNA, which disrupts the complementary pairing between guide RNA (gRNA) and target sequences, leading to cleavage failure; the fourth is the formation of nucleus-like structures, which protects their genomic DNA from degradation by host bacterial CRISPR nucleases. Based on the existing research results, this review proposes that the phage escape rate is the key to improving the efficiency of CRISPR/Cas-mediated phage gene editing. In-depth analysis of the molecular mechanism of phage escape from CRISPR/Cas cleavage can not only provide technical guidance for solving the efficiency bottleneck problem caused by phage escape in gene editing, but also provide insights for the optimization and upgrading of CRISPR/Cas gene editing tools. The systematic summary and analysis of phage escape mechanisms in this paper will not only help to consolidate the theoretical system of the interaction between phages and the CRISPR system, but also provide theoretical support for breaking through technical bottlenecks and promoting the cross-field application of bacteriophage gene editing technology, thereby helping technological innovation in the related industries.
Communication Author：LI Qi , Email:liqi@sicnu.edu.cn
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