体外组装的病毒样颗粒在疫苗和药物递送中的应用

doi:10.19586/j.2095-2341.2022.0108

生物技术进展 ›› 2023, Vol. 13 ›› Issue (2): 201-209.DOI: 10.19586/j.2095-2341.2022.0108

• 进展评述 • 上一篇

体外组装的病毒样颗粒在疫苗和药物递送中的应用

李岩异(), 吕娜, 贾思凝, 张永红, 张红霞, 张卫婷, 陈金利()

华北制药金坦生物技术股份有限公司，石家庄 050035

收稿日期:2022-06-21 接受日期:2022-11-17 出版日期:2023-03-25 发布日期:2023-04-07
通讯作者: 陈金利
作者简介:李岩异 E-mail: 1416305041@qq.com；
基金资助:
河北省重点研发项目(21372403D)

Application of Virus Like Particles Assembled in Vitro in Vaccine and Drug Delivery

Yanyi LI(), Na LYU, Sining JIA, Yonghong ZHANG, Hongxia ZHANG, Weiting ZHANG, Jinli CHEN()

North China Pharmaceutical Jintan Biotechnology Co. ，Ltd. ，Shijiazhuang 050035，China

Received:2022-06-21 Accepted:2022-11-17 Online:2023-03-25 Published:2023-04-07
Contact: Jinli CHEN

摘要/Abstract

摘要：

病毒样颗粒（virus like particles, VLPs）近年来被广泛应用于疫苗和治疗性药物递送系统领域。与体内组装VLPs相比，体外组装VLPs具有组装寡聚体成分明确、反应条件可控、避免宿主成分的引入以及能实现药物活性成分的包裹和递送功能等诸多优势。概述了体外VLPs的生产方法、影响体外VLPs形成的因素、VLPs的特征分析方法，综述了体外VLPs在疫苗和治疗性药物递送方面的应用进展，期望对体外VLPs组装技术的发展提供参考思路，促进体外VLPs组装技术在疾病预防和治疗应用方面发挥更大的作用。

关键词: 衣壳蛋白, 体外组装VLPs, 病毒样颗粒, 药物递送

Abstract:

Virus like particles （VLPs） have been widely used in the field of vaccines and therapeutic drug delivery systems in recent years. Compared with VLPs assembled in vivo， VLPs assembled in vitro have many advantages， such as clear composition of assembled oligomers， controllable reaction conditions， avoiding the introduction of host components， and realizing the encapsulation and delivery of drug active components. This review mainly described the production methods of extracellular VLPs， the influencing factors of VLPs formation， and the characterization methods of VLPs assembled in vitro. The application of VLPs assembled in vitro in vaccine and therapeutic drug delivery was also reviewed. It is expected to provide reference ideas for the development and progress of VLPs assembled in vitro assembly technology， and promote VLPs assembled in vitro assembly technology to play a greater role in disease prevention and treatment.

Key words: capsid protein, VLPs assembled in vitro, virus like particles, drug delivery

中图分类号:

Q815

李岩异, 吕娜, 贾思凝, 张永红, 张红霞, 张卫婷, 陈金利. 体外组装的病毒样颗粒在疫苗和药物递送中的应用[J]. 生物技术进展, 2023, 13(2): 201-209.

Yanyi LI, Na LYU, Sining JIA, Yonghong ZHANG, Hongxia ZHANG, Weiting ZHANG, Jinli CHEN. Application of Virus Like Particles Assembled in Vitro in Vaccine and Drug Delivery[J]. Current Biotechnology, 2023, 13(2): 201-209.

图/表 2

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商品名	生产厂家	生产宿主	结构蛋白	抗原类型	组装方式	临床状态	来源
Gardasil	MERCK	酵母	HPV-L1	HPV6/11/16/18	还原剂解聚/还原剂去除	上市	[64]
Gardasil-9	MERCK	酵母	HPV-L1	HPV6/11/16/18/31/33/45/52/58	还原剂解聚/还原剂去除	上市	[65]
Cervarix	GSK	昆虫细胞	HPV-L1	HPV16/18	多步纯化	上市	[66]
馨可宁	厦门万泰	大肠杆菌	HPV L1	HPV16/18	还原剂去除	上市	[1]
益可宁	厦门万泰	大肠杆菌	HEV p239	HEV E2	还原剂去除	上市	[67]
HPV九价	厦门万泰	大肠杆菌	HPV L1	HPV6/11/16/18/31/33/45/52/58	还原剂去除	临床Ⅲ/CTR20210365	[8]
ENGERIXB/Fendrix	GSK	酵母	HBV/HBsAg	HBsAg	多步纯化	上市	[68]
Recombivax	MERCK	酵母	HBV/HBsAg	HBsAg	多步纯化	上市	[69]
SARS-CoV-2	Novavax	昆虫细胞	SARS-CoV-2/S nanoparticle	SARS-CoV-2 Spike	去污剂去除	上市	[48]
NanoFluTM	Novavax	昆虫细胞	HA nanoparticle	Influenza virus HA	去污剂去除	PhaseⅢ/NCT04120194	https://clinicaltrals.gov

商品名	生产厂家	生产宿主	结构蛋白	抗原类型	组装方式	临床状态	来源
Gardasil	MERCK	酵母	HPV-L1	HPV6/11/16/18	还原剂解聚/还原剂去除	上市	[64]
Gardasil-9	MERCK	酵母	HPV-L1	HPV6/11/16/18/31/33/45/52/58	还原剂解聚/还原剂去除	上市	[65]
Cervarix	GSK	昆虫细胞	HPV-L1	HPV16/18	多步纯化	上市	[66]
馨可宁	厦门万泰	大肠杆菌	HPV L1	HPV16/18	还原剂去除	上市	[1]
益可宁	厦门万泰	大肠杆菌	HEV p239	HEV E2	还原剂去除	上市	[67]
HPV九价	厦门万泰	大肠杆菌	HPV L1	HPV6/11/16/18/31/33/45/52/58	还原剂去除	临床Ⅲ/CTR20210365	[8]
ENGERIXB/Fendrix	GSK	酵母	HBV/HBsAg	HBsAg	多步纯化	上市	[68]
Recombivax	MERCK	酵母	HBV/HBsAg	HBsAg	多步纯化	上市	[69]
SARS-CoV-2	Novavax	昆虫细胞	SARS-CoV-2/S nanoparticle	SARS-CoV-2 Spike	去污剂去除	上市	[48]
NanoFluTM	Novavax	昆虫细胞	HA nanoparticle	Influenza virus HA	去污剂去除	PhaseⅢ/NCT04120194	https://clinicaltrals.gov

系统名称	表达体系	药物成分	靶点	组装方式	参考文献
MS2	大肠杆菌	DOX	肝癌细胞SP94靶点	低pH解聚/中性pH重组	[15]
MS2	大肠杆菌	siRNA	HeLa细胞	低pH解聚中性pH/重组	[71]
P22	大肠杆菌	链霉亲和素/铁蛋白笼	—	变性剂解聚/变性剂	[72]
Qβ	大肠杆菌	荧光蛋白	—	变性剂解聚/变性剂	[19]
HBc	大肠杆菌	DOX	靶向RGD的肿瘤细胞	变性剂解聚/变性剂去除组装	[20]
SV40	昆虫细胞	DNA质粒	—	还原剂解聚/MgCl₂重组	[73]
JC	酵母	RNAi	IL10	渗透压改变	[74]
HPV	昆虫细胞	DNA质粒	—	还原剂解聚/CaCl₂重组	[34]
CCMV	植物/大肠杆菌	SiRNA/Mrna/HRP	FOXA1	高盐解聚/低盐重组	[50]
RV	大肠杆菌	DOX	肝癌细胞	变性剂解聚/醋酸钠缓冲液重组	[15]

系统名称	表达体系	药物成分	靶点	组装方式	参考文献
MS2	大肠杆菌	DOX	肝癌细胞SP94靶点	低pH解聚/中性pH重组	[15]
MS2	大肠杆菌	siRNA	HeLa细胞	低pH解聚中性pH/重组	[71]
P22	大肠杆菌	链霉亲和素/铁蛋白笼	—	变性剂解聚/变性剂	[72]
Qβ	大肠杆菌	荧光蛋白	—	变性剂解聚/变性剂	[19]
HBc	大肠杆菌	DOX	靶向RGD的肿瘤细胞	变性剂解聚/变性剂去除组装	[20]
SV40	昆虫细胞	DNA质粒	—	还原剂解聚/MgCl₂重组	[73]
JC	酵母	RNAi	IL10	渗透压改变	[74]
HPV	昆虫细胞	DNA质粒	—	还原剂解聚/CaCl₂重组	[34]
CCMV	植物/大肠杆菌	SiRNA/Mrna/HRP	FOXA1	高盐解聚/低盐重组	[50]
RV	大肠杆菌	DOX	肝癌细胞	变性剂解聚/醋酸钠缓冲液重组	[15]

体外组装的病毒样颗粒在疫苗和药物递送中的应用

Application of Virus Like Particles Assembled in Vitro in Vaccine and Drug Delivery

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