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

Abstract

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.

Figure 1

Diagram depicting the molecular mechanism of gene silencing by RNAi. Inside the cell, the introduced long dsRNA is cleaved by nucleases into small interfering RNAs (siRNAs). SiRNAs are loaded into the RISC complex which promotes the cleavage of target mRNA, thus inducing silencing of the target gene.