摘要
RNA复制子是自主复制的RNA ,保留了病毒复制酶基因 ,而结构蛋白基因缺失 ,由外源抗原基因取代 ,复制酶可控制载体RNA在胞浆中高水平复制和外源基因的高水平表达。用于开发复制子的主要是单股正链RNA病毒 ,如甲病毒 (辛德比斯病毒、塞姆利基森林病毒、委内瑞拉马脑炎病毒 )、黄病毒 (登革热病毒、昆津病毒 )、小RNA病毒 (脊髓灰质炎病毒、人鼻病毒 )、副粘病毒 (犬瘟热病毒 )、杯状病毒 (猫杯状病毒 )。基于复制子的疫苗不会产生能复制的感染性病毒粒子 ,不可能与细胞基因组发生整合 ,但可诱导全身免疫和粘膜免疫以及MHC I限制性CTL反应 ,而不受体内已有载体抗体的干扰。目前已开发了大量基于复制子的疫苗和肿瘤的治疗性和预防性疫苗 ,并在很多疾病模型上取得成功 ,包括病毒 (流感病毒、人免疫缺陷病毒、拉沙病毒、马尔堡病毒、呼吸道合胞体病毒、诺沃克样病毒、马动脉炎病毒等 )肿瘤 (人乳头瘤、癌胚抗原、B1 6肿瘤、小鼠黑素瘤等 )、以及细菌毒素 (肉毒杆菌毒素、葡萄球菌肠毒素、破伤风毒素等 )。
RNA replicon is a kind of self-replicating viral RNA,in which genes coding for viral replicases are reserved while genes coding for structure proteins are replaced by foreign gene(s).High-level replication of RNA and expression of foreign gene(s)in cytoplasm are regulated by the replicases.Many single-strand RNA viruses have been developed as replicons,among which are alphaviruses(Sindbis virus,Semliki Forest virus,Venezuelan equine encephalitis virus),flaviviruses(dengue virus and Kunjin virus),picornaviruses(poliovirus,human rhinovirus),paramyxoviruses(canine ditemper virus)、caliciviruses(feline calicivirus).Repicon-based vaccines,also called as suicidal vaccines,are unable to produce replication-competent infectious viruses,nor are they capable of integrating the RNA into cell genome.However,they can induce systemic and mucosal immunity and MHC-1-restricted cytotoxic T lymphocytes antibody even in the presence of antibodies to vector viruses.Up to now,many replicon-based vaccines are developed as therapeutic and preventive vaccines against infectious diseases or cancers,which shows promise in many models,such as viruses(influenza virus,HIV-1,Lassa virus,Marburg virus,human respiratory syncytial virus,Norwalk-like virus,equine arterivirus,etc),tumors(human papilloma,CEA,B16,mouse melanoma,etc) and bacterial toxins(BoNT/A,SEB,tetanus toxin C,etc).;
出处
《中国生物工程杂志》
CAS
CSCD
2003年第3期44-49,共6页
China Biotechnology
