title: A novel minicircle vector based system for inhibting the replication and gene expression of enterovirus 71 and coxsackievirus A16.
abstract: Enterovirus 71 (EV 71) and Coxsackievirus A16 (CA 16) are two major causative agents of hand, foot and mouth disease (HFMD). They have been associated with severe neurological and cardiological complications worldwide, and have caused significant mortalities during large-scale outbreaks in China. Currently, there are no effective treatments against EV 71 and CA 16 infections. We now describe the development of a novel minicircle vector based RNA interference (RNAi) system as a therapeutic approach to inhibiting EV 71 and CA 16 replication. Small interfering RNA (siRNA) molecules targeting the conserved regions of the 3C(pro) and 3D(pol) function gene of the EV 71 and CA 16 China strains were designed based on their nucleotide sequences available in GenBank. This RNAi system was found to effectively block the replication and gene expression of these viruses in rhabdomyosarcoma (RD) cells and virus-infected mice model. The inhibitory effects were confirmed by a corresponding decrease in viral RNA, viral protein, and progeny virus production. In addition, no significant adverse off-target silencing or cytotoxic effects were observed. These results demonstrated the potential and feasibility of this novel minicircle vector based RNAi system for antiviral therapy against EV 71 and CA 16 infection.
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Yang
authors.forename: Guodong
authors.initials: G
authors.lastname: Li
authors.forename: Yingqiu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xiaoman
authors.initials: X
authors.lastname: Liu
authors.forename: Po
authors.initials: P
authors.lastname: Tien
mesh_terms: D000818:Animals; D001688:Biological Products / Q000008:administration & dosage; D002460:Cell Line; D004195:Disease Models, Animal; D004770:Enterovirus / Q000235:genetics / Q000502:physiology*; D029821:Enterovirus A, Human / Q000235:genetics / Q000502:physiology*; D015967:Gene Expression Regulation, Viral; D015684:Gene Products, pol / Q000037:antagonists & inhibitors; D020868:Gene Silencing; D005822:Genetic Vectors; D006232:Hand, Foot and Mouth Disease / Q000628:therapy; D006801:Humans; D051379:Mice; D010447:Peptide Hydrolases / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D016896:Treatment Outcome; D014779:Virus Replication
chemical_list: D001688:Biological Products; D015684:Gene Products, pol; D034741:RNA, Small Interfering; D010447:Peptide Hydrolases