Silencing of HIV-1 with RNA Interference: a Multiple shRNA Approach

摘要: Double-stranded RNA can induce gene silencing via a process known as interference (RNAi). Previously, we have shown that stable expression of single shRNA targeting the HIV-1 Nef strongly inhibits replication. However, this was not sufficient to maintain inhibition. One hallmarks RNAi, its sequence specificity, presented way out for virus, nucleotide substitutions in target region abolished For development durable therapy prevents viral escape, proposed combine multiple shRNAs against conserved regions. Therefore, screened 86 different highly We identified act potent inhibitors virus show, first time, three from lentiviral vector results similar levels inhibition per compared vectors. Thus, their combined much stronger production. Moreover, when infected cells transduced with double vector, escape delayed. These confirm RNAi has great potential an antiviral approach and support our efforts develop strategy treatment HIV-1-infected individuals.