Research Progress in the Expression of Recombinant Proteins in Endosperm Bioreactors

doi:10.13560/j.cnki.biotech.bull.1985.2025-1022

Abstract

Abstract:

The plant expression system has emerged as an ideal platform for producing recombinant proteins and bioactive metabolites—such as therapeutic proteins, vaccines, enzymes, antibodies, vitamins, flavonoids, and carotenoids—due to its low cost, sustainability, scalability, safety, and environmental friendliness. Among these systems, the plant endosperm is considered as a high-quality bioreactor for synthesizing and storing active substances because of its natural biosynthetic and storage capabilities. This article provides a systematic review of the applications of plant endosperm bioreactors in molecular agriculture and highlights their comprehensive advantages compared to other mainstream expression systems. It focuses on recent research advancements and practical applications involving the production of therapeutic proteins, enzymes, antibodies, and vaccines using endosperm bioreactors. To address the challenge of low expression levels of target proteins in the endosperm system, the article explores optimization strategies aimed at enhancing transcription efficiency. Furthermore, it systematically analyzes the use of glycosylation metabolic engineering to achieve humanized modifications, thereby mitigating the immunogenicity issues associated with plant-derived drugs. Finally, the article discusses key factors currently limiting the commercialization of transgenic plant-derived products, such as regulatory hurdles, public acceptance, and purification costs, and offers a forward-looking perspective on the future development of this technology, emphasizing its significant potential for producing high-value bioproducts using endosperm.

Key words: endosperm bioreactor, plant bioreactor, recombinant protein, promoter, glycosylation modification

LI Can-ni, PAN Wei-song, WU Tai-ru, WU Chuan, Keung Eric Tsang Po, LI Wei-zhan. Research Progress in the Expression of Recombinant Proteins in Endosperm Bioreactors[J]. Biotechnology Bulletin, 2026, 42(7): 67-80.

Figures/Tables 3

References 34

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名称Name	表达系统Expression system	临床研究阶段进展及结果Progress and results of clinical research stage	参考文献 References
四价流感病毒	H1、H3和两种B血凝素蛋白作为VLPs在本氏烟草中瞬时表达	临床Ⅲ期，由于该疫苗未达到对匹配菌株引起的呼吸道疾病的70%绝对疫苗效力，已终止	［4］
埃博拉病毒疫苗	通过快速瞬时转化在本氏烟草中表达3种植物中和性的单克隆抗体鸡尾酒以生产ZMapp来对抗埃博拉	临床Ⅱ/Ⅲ期已完成，已于2022年12月21日获得FDA审批	［5］
轮状病毒疫苗	轮状病毒的四种结构抗原（VP2、VP4、VP6和VP7）作为VLPs在植物中表达	临床Ⅰ期已终止，20名志愿者中19人产生免疫反应	［6］
狂犬病病毒疫苗	GP/NP抗原在菠菜中表达	临床Ⅰ期早期已终止，受试者9人中有5人对狂犬病毒表现出显著抗体反应	［7］
乙型肝炎病毒疫苗	HBsAg在莴苣中表达	临床Ⅰ期早期已终止，第一次志愿者血清中未检测出显著的水平的特异性抗体；第二次血清检测到其特异性抗体效价超3 IU/L	［8］
乙型肝炎病毒疫苗	HBsAg在马铃薯中表达	临床Ⅰ期已终止，16名志愿者中10人食用三剂转基因马铃薯后血清抗HBsAg滴度上升；17名志愿者中9人食用两剂转基因马铃薯后血清抗HBsAg滴度上升	［9］
诺沃克病毒疫苗	CP在马铃薯中表达	临床Ⅰ期早期，20名志愿者中19名出现特异性IgA抗体分泌细胞数量显著增加；4名志愿者出现特异性血清IgG；6名出现特异性排泄物IgA	［10］
霍乱细菌疫苗	CTB抗原在水稻中表达	临床Ⅰ期，50%-70%的接种者产生了针对CTB的特异性血清IgG抗体，30%-50%的接种者的粪便样本中检测到了针对CTB的特异性分泌型IgA抗体	［11］
新城疫疫苗	血凝素-神经氨酸酶蛋白的功能结构域在烟草细胞BY-2中表达	2006年已获得美国农业部的商业审批，接种该植物源HN蛋白疫苗后，能够诱导产生高水平的、针对新城疫病毒HN蛋白的特异性血清抗体	［12］
SARS-CoV-2疫苗	重组刺突糖蛋白作为VLPs在本氏烟草中表达	2022年已获得加拿大卫生部的审批，该疫苗对有症状COVID-19的总体有效性为71.6%，但由于其母公司的资金存在困难，最终在2023年初宣布停止所有运营并关闭	［13］

名称Name	表达系统Expression system	临床研究阶段进展及结果Progress and results of clinical research stage	参考文献 References
四价流感病毒	H1、H3和两种B血凝素蛋白作为VLPs在本氏烟草中瞬时表达	临床Ⅲ期，由于该疫苗未达到对匹配菌株引起的呼吸道疾病的70%绝对疫苗效力，已终止	［4］
埃博拉病毒疫苗	通过快速瞬时转化在本氏烟草中表达3种植物中和性的单克隆抗体鸡尾酒以生产ZMapp来对抗埃博拉	临床Ⅱ/Ⅲ期已完成，已于2022年12月21日获得FDA审批	［5］
轮状病毒疫苗	轮状病毒的四种结构抗原（VP2、VP4、VP6和VP7）作为VLPs在植物中表达	临床Ⅰ期已终止，20名志愿者中19人产生免疫反应	［6］
狂犬病病毒疫苗	GP/NP抗原在菠菜中表达	临床Ⅰ期早期已终止，受试者9人中有5人对狂犬病毒表现出显著抗体反应	［7］
乙型肝炎病毒疫苗	HBsAg在莴苣中表达	临床Ⅰ期早期已终止，第一次志愿者血清中未检测出显著的水平的特异性抗体；第二次血清检测到其特异性抗体效价超3 IU/L	［8］
乙型肝炎病毒疫苗	HBsAg在马铃薯中表达	临床Ⅰ期已终止，16名志愿者中10人食用三剂转基因马铃薯后血清抗HBsAg滴度上升；17名志愿者中9人食用两剂转基因马铃薯后血清抗HBsAg滴度上升	［9］
诺沃克病毒疫苗	CP在马铃薯中表达	临床Ⅰ期早期，20名志愿者中19名出现特异性IgA抗体分泌细胞数量显著增加；4名志愿者出现特异性血清IgG；6名出现特异性排泄物IgA	［10］
霍乱细菌疫苗	CTB抗原在水稻中表达	临床Ⅰ期，50%-70%的接种者产生了针对CTB的特异性血清IgG抗体，30%-50%的接种者的粪便样本中检测到了针对CTB的特异性分泌型IgA抗体	［11］
新城疫疫苗	血凝素-神经氨酸酶蛋白的功能结构域在烟草细胞BY-2中表达	2006年已获得美国农业部的商业审批，接种该植物源HN蛋白疫苗后，能够诱导产生高水平的、针对新城疫病毒HN蛋白的特异性血清抗体	［12］
SARS-CoV-2疫苗	重组刺突糖蛋白作为VLPs在本氏烟草中表达	2022年已获得加拿大卫生部的审批，该疫苗对有症状COVID-19的总体有效性为71.6%，但由于其母公司的资金存在困难，最终在2023年初宣布停止所有运营并关闭	［13］