RNA interference (RNAi) has emerged as a powerful tool to manipulate gene expression in the laboratory. The presence of a double-stranded RNA (dsRNA) in eukaryotic cells triggers this post-transcriptional gene-silencing mechanism, leading to a sequence-specific degradation of the target mRNA. Among its many potential biomedical applications, silencing of viral genes stands out as a promising therapeutic strategy. Marine shrimp viral diseases, especially white spot disease (WSD), represents one of the most attractive targets for the development of therapeutic RNAi owing to its widespread economic impact. This review summarizes the current knowledge in the therapeutic application of RNAi for combating viral diseases in shrimp. The basic principles of RNAi are described, focusing on features important for its therapeutic manipulation. Subsequently, a stepwise strategy for the development of therapeutic RNAi is presented.KEY WORDS: RNAi therapy · Shrimp diseases · Small interfering RNA · siRNA · Long hairpin RNA · lhRNA
Resale or republication not permitted without written consent of the publisherDis Aquat Org 86: [263][264][265][266][267][268][269][270][271][272] 2009 exception of MSGS, are classified as OIE notifiable (OIE 2006). Among these, WSSV has had the greatest impact on shrimp farming and is currently considered the most important shrimp disease in terms of distribution and economic losses.
Current therapeutic strategiesManaging viral diseases has been the greatest challenge to the shrimp industry because short-term strategies, such as the use of immunostimulants, bioremediators and probiotics, have their own limitations in terms of their efficacy, practicability, cost, and, above all, reproducibility. Unlike finfishes, the shrimps lack a developed adaptive immune system, which is a prerequisite for the development of any protein vaccines. Subunit vaccines (Witteveldt et al. 2004a(Witteveldt et al. ,b, 2006 have been reported to provide some degree of protection to shrimps from viral infection, but their field level potential is yet to be seen. In this scenario, RNAi, which seems to offer great promise in terms of treating human and animal diseases, is looked upon with great hope by shrimp health managers.
ENDOGENOUS RNAi PATHWAYObservations were made in plants (Napoli et al. 1990, van der Krol et al. 1990) and nematodes (Lee et al. 1993),which hinted at the existence of the RNAi pathway years before double-stranded RNA (dsRNA) molecules were identified as the key component of this evolutionarily conserved post-transcriptional silencing pathway in eukaryotic cells (Fire et al. 1998). Since then, we have witnessed significant advances in the understanding of how RNAi functions and identified several effective ways to manipulate it in the laboratory. Although a detailed account on the mechanistic aspects of RNAi is beyond the scope of this review and can be found elsewhere (Bartel 2004, Carmell & Hannon 2004, Cullen 2004, Meister & Tuschl 2004, Murchison & Hannon 2004, Du & Zamore 2005, Kim 20...