流感病毒改造新策略及其应用

郭茜亚; 陈积; 董铭心

doi:10.12211/2096-8280.2023-078

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流感病毒改造新策略及其应用

特约评述 | 更新时间：2025-03-20

- 流感病毒改造新策略及其应用
- New strategies for engineering influenza viruses and their applications
- 合成生物学 2024年5卷第2期页码：267-280
- 作者机构：
  
  青岛大学药学院药物化学系，山东青岛 266000
- 作者简介：
  
  [ "郭茜亚（1997—），女，博士研究生。研究方向为溶瘤病毒的研发策略及应用。E-mail：guoxiya132@163.com" ]
  [ "董铭心（1978—），男，教授，博士生导师。研究方向为抗病毒和神经系统小分子药物及疫苗。E-mail：Mxdong64@qdu.edu.cn" ]
- 基金信息：
  
  国家重点研发计划“合成生物学”重点专项(2018YFA0900804)
- DOI：10.12211/2096-8280.2023-078
  中图分类号： R915
- 收稿：2023-11-09，
  
  修回：2024-02-22，
  
  纸质出版：2024-04-30
- 稿件说明：
移动端阅览
郭茜亚，陈积，董铭心. 流感病毒改造新策略及其应用［J］. 合成生物学， 2024， 5（2）： 267-280

GUO Xiya， CHEN Ji， DONG Mingxin. New strategies for engineering influenza viruses and their applications［J］. Synthetic Biology Journal， 2024， 5（2）： 267-280
郭茜亚，陈积，董铭心. 流感病毒改造新策略及其应用［J］. 合成生物学， 2024， 5（2）： 267-280 DOI： 10.12211/2096-8280.2023-078.

GUO Xiya， CHEN Ji， DONG Mingxin. New strategies for engineering influenza viruses and their applications［J］. Synthetic Biology Journal， 2024， 5（2）： 267-280 DOI： 10.12211/2096-8280.2023-078.

摘要

流感病毒有着极强的变异性和传播性，常在全球范围内引起季节性的流感爆发。流感病毒的基因组序列、蛋白结构与功能、病毒的包装机制等环节研究相对清楚，也是一种重要的模式病毒，用于条件控制基因元件的发现和确证，构建智能响应型病毒等。随着反向遗传学与合成生物学的发展，通过基因工程改造的流感病毒能更好地控制病毒复制来提高疫苗的安全性，以及诱发机体产生强烈的免疫反应，在肿瘤免疫治疗领域引发广泛关注。本文描述了蛋白质水解靶向嵌合病毒、条件复制型流感减毒活病毒和高干扰素敏感病毒等三种新型减毒流感病毒改造策略，并对编码过早终止密码子的嵌合抗原肽的流感病毒、与PD-L1或CTLA4免疫检查点重组的流感病毒、截短的NS1片段表达GM-CSF的流感病毒分别对黑色素瘤、肝癌的溶瘤作用进行评述。未来，将通过创新性地运用不同策略、不同病毒来构建减毒活疫苗和溶瘤病毒，以便在临床上获得更加安全有效的治疗手段。

Abstract

Influenza viruses are highly variable and transmissible

and their infections can cause infectious respiratory diseases

such as seasonal influenza outbreaks around the world

one of the most serious public health problems at present

which can be prevented by influenza vaccination. The genome sequences

protein structures and functions of influenza viruses

as well as their packaging mechanisms are relatively clear. they are also important models

which can be used for developing conditional control genetic elements and the construction of intelligent responsive viruses. With the development of reverse genetics and synthetic biology technology

influenza viruses that are genetically engineered can better control virus replication to improve the safety of vaccines

and induce strong immune responses in human being

which have attracted wide attention in tumor immunotherapy. Several studies using simple or modified influenza viruses for treating liver cancer

melanoma

or lung cancer have found breakthroughs. In this paper

three novel strategies for attenuating influenza viruses

namely

proteolytic targeted chimeric virus

conditionally replicating influenza-attenuated live virus and highly interferon-sensitive virus

are described. The oncolytic effects of influenza viruses encoding premature stop codon chimeric antigen peptide

influenza viruses recombining with PD-L1 or CTLA4 immune checkpoint and influenza viruses expressing GM-CSF with truncated NS1 fragment on melanoma and hepatocellular carcinoma are reviewed

respectively

which suggest that the influenza viruses can be used as a live attenuated vaccine and a potential carrier for oncolytic viruses

and future researchers can be focused on constructing influenza viruses with more innovative strategies and different viruses to build a live attenuated vaccine and oncolytic viruses

in order to obtain high safety and more clinical curative treatment

improving the life quality of the patients.

关键词

Keywords

references

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