Adeno-Associated Viruses Serotype 2-Mediated RNA Interference Efficiently Inhibits Rabies Virus Replication In Vitro and In Vivo

WU, Hong-Xia; WANG, Hua-Lei; GUO, Xiao-Feng; YANG, Yu-Jiao; MA, Jin-Zhu; WANG, Tie-Cheng; GAO, Yu-Wei; ZHAO, Yong-Kun; YANG, Song-Tao; XIA, Xian-Zhu

In this study, we developed a universal siRNA agent that would recognize different RABV strains by using the N gene, which is the most highly conserved gene among the five RABV genes [21] . Moreover, we selected the most conserved sequences of the N transcript for use as RNAi targets. widely used in delivering various genes and siRNAs. but, these viral vectors could stimulate host immune response and produce a specific antibody against viral vectors, which would restrict the use again in the same host. In addition to unwanted activation of the immune response, the safety concerns also involve off-targeting effects. AAV vectors have been highly successful in overcoming these disadvantages. They are currently among the most frequently used viral vectors for gene therapy. Twelve human serotypes of AAV (AAV-1 to AAV-12) and more than 100 serotypes from nonhuman primates have been discovered to date [4] . The characterization of new AAV serotypes has revealed that they have different patterns of transduction in diverse tissues [3] . AAV has become increasingly common as a vector for use in human clinical trials, such as immunodeficiency disease [5] , muscle directed gene therapy [6] and lung disease [12] . AAV-2-based rAAV vectors can transduce muscle, the liver, the brain, the retina and the lungs [4] . rAAV2 has emerged as a vector of choice for gene transfer to the central nervous system, because of its strong neuronal tropism and lack of pathogenicity in mammals [4] . Moreover, AAV-2 has been shown to induce a weak cellmediated immune response. This may be attributed to AAV inefficiently infecting mature dendritic cells (DC) [22] . So, in this study, we made use of an AAV-2 vector to deliver the siRNA targeting the RAbV N gene. The results in the in vitro (NA cells) and in vivo (mice brain and muscle) experiments showed that AAV-2 can work as a good siRNA delivery tool.