噬菌体基因工程技术与应用研究进展

doi:10.19586/j.2095-2341.2024.0138

生物技术进展 ›› 2025, Vol. 15 ›› Issue (2): 189-200.DOI: 10.19586/j.2095-2341.2024.0138

• 进展评述 • 上一篇

噬菌体基因工程技术与应用研究进展

焦耀萱, 李敏(), 屈昕雅, 刘恬伶, 生秀梅, 周晓祥()

江苏大学医学院，江苏镇江 212013

收稿日期:2024-08-22 接受日期:2024-12-27 出版日期:2025-03-25 发布日期:2025-04-29
通讯作者: 周晓祥
作者简介:李敏 E-mail: limin@ujs.edu.cn；
基金资助:
中国博士后科学基金资助项目(2023M731366);江苏省自然科学基金项目(BK20230527)

Advances on Phage Genetic Engineering Technology and Applications

Yaoxuan JIAO, Min LI(), Xinya QU, Tianling LIU, Xiumei SHENG, Xiaoxiang ZHOU()

School of Medicine，Jiangsu University，Jiangsu Zhenjiang 212013，China

Received:2024-08-22 Accepted:2024-12-27 Online:2025-03-25 Published:2025-04-29
Contact: Xiaoxiang ZHOU

摘要/Abstract

摘要：

抗生素耐药性已成为全球人类健康面临的重大威胁，医药、工业、农业生产以及生态等领域均受到多重耐药菌的严重威胁。多重耐药菌感染逐渐呈现高发病率、高死亡率的趋势。噬菌体可以特异性裂解多重耐药病原菌，然而由于噬菌体宿主谱狭窄、基因组中含有不利基因等因素的制约，当前只有部分噬菌体成功应用于防治多重耐药菌感染等领域。噬菌体基因工程具有可编辑、高效等优势，为拓宽噬菌体宿主谱、设计“安全、绿色、高效”的新型噬菌体提供了理论基础。综述了噬菌体基因工程技术的研究进展，以及噬菌体在临床抗耐药菌感染、农业生产和生态环境等方面的实际应用，为噬菌体的定向改造及其在各领域中的有效应用提供了理论支持和参考。

关键词: 噬菌体, 基因重组, 基因编辑, 多重耐药, 噬菌体疗法

Abstract:

Antibiotic resistance has become one of the most critical threats to global health. The emergence of multi-drug resistant bacterial infections has led to increasingly high morbidity and mortality rates across medical， industrial， agricultural， and ecological domains. Phages can specifically lyse multi-drug resistant pathogens. However， due to their narrow host range， the presence of unfavorable genes in their genomes， and other limitations， only a limited number of phages have been successfully applied to combat multidrug-resistant bacterial infections. With editable and efficient features， phage genetic engineering provides a promising approach for expanding phage host ranges and designing "safe， green， and efficient" novel phages. This review systematically summarized recent advances in phage genetic engineering technologies while highlighting their practical applications in clinical therapies against drug-resistant infections， agricultural production， and ecological remediation. These insights established theoretical foundations for phage modification and their effective utilization in diverse fields.

Key words: bacteriophage, genetic recombination, genome editing, multidrug resistance, phage therapy

中图分类号:

Q939.48

焦耀萱, 李敏, 屈昕雅, 刘恬伶, 生秀梅, 周晓祥. 噬菌体基因工程技术与应用研究进展[J]. 生物技术进展, 2025, 15(2): 189-200.

Yaoxuan JIAO, Min LI, Xinya QU, Tianling LIU, Xiumei SHENG, Xiaoxiang ZHOU. Advances on Phage Genetic Engineering Technology and Applications[J]. Current Biotechnology, 2025, 15(2): 189-200.

图/表 2

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方式	噬菌体	具体策略	参考文献	年份
经典同源重组	T4	通过基因片段重组配对修复被CRISPR切割破坏的基因组	[10]	2021
	T2	改造尾丝蛋白Gp38的结构	[11]	2004
	T7	与相应质粒的同源重组构建工程化的T7噬菌体	[12]	2020
	T7	特异性改造RBP	[12]	2021
CRISPR/Cas	T4	V型CRISPR/Cas12a系统编辑T4噬菌体基因组	[13]	2021
	T5	由Retron介导的诱变方案	[14]	2021
	T7	I~E型CRISPR/Cas系统编辑T7噬菌体基因组	[15]	2014
	需钠弧菌噬菌体TT4	CRISPR/Cas9系统编辑TT4噬菌体基因组	[16]	2022
	大肠杆菌噬菌体	CRISPR/Cas13a+抗CRISPR基因（acrVIA1）	[17]	2022
	φKZ、OMKO1和PaMx41噬菌体	CRISPR/Cas13a+正向选择基因acrVIA1	[18]	2022
BRED	分枝杆菌噬菌体BPs、ZoeJ	使温和噬菌体改造为烈性噬菌体	[19]	2019
	T7	基因组进行单碱基改变和整个基因替换	[20]	2020
	温和沙门氏菌噬菌体	进行裂解转换和溶原转换	[21]	2014
	克雷伯氏菌噬菌体	建立了克雷伯氏菌噬菌体基因组的重组系统	[22]	2017
YAC	铜绿假单胞菌噬菌体	噬菌体基因组的基因敲除	[23]	2020
	PICIs	快速编辑酿酒酵母中的PICIs	[24]	2020
pORTMAGE	T5、T7、P1和λ噬菌体	噬菌体基因组单碱基替换、插入	[25]	2023

方式	噬菌体	具体策略	参考文献	年份
经典同源重组	T4	通过基因片段重组配对修复被CRISPR切割破坏的基因组	[10]	2021
	T2	改造尾丝蛋白Gp38的结构	[11]	2004
	T7	与相应质粒的同源重组构建工程化的T7噬菌体	[12]	2020
	T7	特异性改造RBP	[12]	2021
CRISPR/Cas	T4	V型CRISPR/Cas12a系统编辑T4噬菌体基因组	[13]	2021
	T5	由Retron介导的诱变方案	[14]	2021
	T7	I~E型CRISPR/Cas系统编辑T7噬菌体基因组	[15]	2014
	需钠弧菌噬菌体TT4	CRISPR/Cas9系统编辑TT4噬菌体基因组	[16]	2022
	大肠杆菌噬菌体	CRISPR/Cas13a+抗CRISPR基因（acrVIA1）	[17]	2022
	φKZ、OMKO1和PaMx41噬菌体	CRISPR/Cas13a+正向选择基因acrVIA1	[18]	2022
BRED	分枝杆菌噬菌体BPs、ZoeJ	使温和噬菌体改造为烈性噬菌体	[19]	2019
	T7	基因组进行单碱基改变和整个基因替换	[20]	2020
	温和沙门氏菌噬菌体	进行裂解转换和溶原转换	[21]	2014
	克雷伯氏菌噬菌体	建立了克雷伯氏菌噬菌体基因组的重组系统	[22]	2017
YAC	铜绿假单胞菌噬菌体	噬菌体基因组的基因敲除	[23]	2020
	PICIs	快速编辑酿酒酵母中的PICIs	[24]	2020
pORTMAGE	T5、T7、P1和λ噬菌体	噬菌体基因组单碱基替换、插入	[25]	2023

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噬菌体基因工程技术与应用研究进展

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