title: Aptamers targeting rabies virus-infected cells inhibit viral replication both in vitro and in vivo.
abstract: Rabies is an acute fatal encephalitis disease that affects many warm-blooded mammals. The causative agent of the disease is Rabies virus (RABV). Currently, no approved therapy is available once the clinical signs have appeared. Aptamers, oligonucleotide ligands capable of binding a variety of molecular targets with high affinity and specificity, have recently emerged as promising therapeutic agents. In this study, sixteen high-affinity single-stranded DNA (ssDNA) aptamers were generated by cell-SELEX. Viral titer assays revealed aptamers could specifically inhibit the replication of RABV in cells but did not inhibit the replication of canine distemper virus or canine parvovirus. In addition, the FO21 and FO24 aptamers, with and without PEGylation, were found to effectively protect mice against lethal RABV challenge. When mice were inoculated with aptamers for 24h prior to inoculation with CVS-11, approximately 87.5% of the mice survived. Here, we report aptamers that could significantly protect the mice from a lethal dose of RABV in vitro and in vivo, as demonstrated by the results for survival rate, weight loss and viral titers. These results indicate that FO21 and FO24 aptamers are a promising agent for specific antiviral against RABV infections.
authors: Institute of Military Veterinary Medicine, Academy of Military Medical Science, Changchun 130062, China.
authors: Hong-Ru
authors: HR
authors: Liang
authors: Quan
authors: Q
authors: Liu
authors: Xue-Xing
authors: XX
authors: Zheng
authors: Wei-Wei
authors: WW
authors: Gai
authors: Xiang-hong
authors: XH
authors: Xue
authors: Gui-Qiu
authors: GQ
authors: Hu
authors: Hong-Xia
authors: HX
authors: Wu
authors: Hua-Lei
authors: HL
authors: Wang
authors: Song-Tao
authors: ST
authors: Yang
authors: Xian-Zhu
authors: XZ
authors: Xia
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000494:pharmacology; D052157:Aptamers, Nucleotide / Q000008:administration & dosage* / Q000494:pharmacology; D004195:Disease Models, Animal; D004217:Distemper Virus, Canine / Q000187:drug effects; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D017993:Parvovirus, Canine / Q000187:drug effects; D011818:Rabies / Q000517:prevention & control*; D011820:Rabies virus / Q000187:drug effects* / Q000502:physiology; D016019:Survival Analysis; D019562:Viral Load; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D052157:Aptamers, Nucleotide