Applications of RNA Interference in Schistosomiasis: Gene Function Identification and Development of New Therapies

The study of Schistosoma species has undergone a dramatic change in recent years mainly due to transcriptome, proteome, and genome analyses. In order to better understand the biology of the parasite and to develop new and more efficient/specific drugs, scientists have now the task to translate genetic information into functional data. The present paper aims to review the use of RNA interference (RNAi), a versatile technique used in gene silencing, for the dissection of the cellular/molecular biology of Schistosoma spp. In addition, we will review information on the recent development of a new generation of RNA-based drugs. Examples of specific experimental approaches will be presented and discussed, such as identification of gene function, development of therapies by targeting eggs, miracidia (as a strategy for environmental use), sporocysts (for infestation control in the intermediate host), and schistosomula/adult worms (as a treatment strategy). Furthermore, some of the main advantages, drawbacks, and future directions of these new applications and techniques will also be discussed. 1. Introduction The study of Schistosoma species and schistosomiasis has undergone a dramatic change in recent years. Since the first published transcriptome [1, 2], proteome [3], and genome analyses [4–6], a large amount of data has been available in the literature. In order to better understand the biology of Schistosoma spp. and to develop new and more efficient/specific drugs, scientists are now faced with the big challenge of translating genetic information into functional data. This paper aims to review the use of a powerful technique named RNA interference (RNAi) for the dissection of the cellular and molecular biology of Schistosoma spp. In addition, the rationale behind the development and the potential applications of a new class of RNA-based drugs will be discussed. 2. The Technology of RNA Interference RNAi is a technique by which the introduction of double-stranded RNAs (dsRNAs) promotes potent posttranscriptional gene silencing (Figure 1). It was first observed in the free living nematode C. elegans, after injections of long dsRNAs in the gonad of the worm, leading to the cleavage of specific messenger RNA (mRNA) while keeping other genes unaffected [7]. As a direct consequence of mRNA cleavage, a specific phenotype arises shortly after, such as sterility, lethargy, developmental arrest, or lethality (depending on the target gene). Figure 1: Diagram depicting the molecular mechanism of gene silencing by RNAi. Inside the cell, the introduced long dsRNA is