Antiviral RNAi: How to Silence Viruses (original) (raw)

RNAi is a cellular mechanism that can be induced by siRNAs to mediate the sequence-specific gene knockdown by cleavage or translational repression of the targeted mRNA. The initial phenomenon that led to the discovery of RNAi was made by Jorgensen and colleagues in petunia flowers that turned partially or completely white after the introduction of a pigment-producing gene that was supposed to deepen the purple color [1]. Around the same time, van der Krol et al. reported similar observations in petunias [2]. Soon thereafter, similar phenomena were described in the fungi Neurospora crassa by Romano and Macino, where this posttranscriptional gene silencing (PTGS) is also known as quelling [3]. Fire et al. described the RNAi phenomenon in mechanistic terms in the nematode Caenorhabditis elegans. Efficient sequence-specific gene silencing was observed upon introduction of double-stranded RNA (dsRNA) [4]. Injection of dsRNA corresponding to different genes resulted in a specific null mutant phenotype in Drosophila [5, 6]. Subsequently, RNAi was also described in Trypanosoma brucei [7], zebrafish [8], and mice [9]. Introduction of base paired 21-nucleotide dsRNA into mammalian cell lines also triggered sequencespecific gene silencing [10]. This discovery triggered the development of RNAi-based therapies against a wide variety of diseases, including cancer, neurological, autoimmune, and infectious diseases [11-17]. 13.2 Therapeutic Application of the RNAi Mechanism Antiviral Drug Strategies, First Edition. Edited by Erik De Clercq.