Introduction: Advances in scientific research have enabled gene modification in living organisms. RNA interference (RNAi) has become a preferred method for targeted gene silencing in the treatment of diseases caused by infectious agents. In particular, neglected tropical diseases (NTDs) may benefit from RNAi approaches, as their causative organisms often present complex life cycles, offering multiple developmental stages that can be targeted to interrupt disease progression. This review systematically compiles and integrates studies on the application of RNAi, especially small interfering RNA (siRNA), in NTDs, highlighting its effectiveness through in vitro and in vivo evidence. Methods: Four bibliographic databases, Science Direct, PubMed, CAPES Journals, and Web of Science, were used to search. The selection of studies and the writing of this systematic review followed the criteria outlined by the PRISMA guidelines. Results: A total of 4559 articles, from which 61 were selected. The main diseases found were schistosomiasis, malaria, filariasis, leishmaniasis, and Chagas disease. Discussion: The integration of the studies demonstrated that RNAi is applied both to the parasite, compromising its behavior, structure, and functional development, and to intermediate and final hosts, to prevent parasitism and proliferation. Nevertheless, translational limitations and the route of administration must be considered, for instance. Conclusion: Thus, although the application of RNAi is promising for the treatment of NTDs, studies are needed to elucidate safe and effective delivery mechanisms, as well as to encourage research into the treatment of NTDs using new therapies that are not entirely drug-based
Melo et al. (Fri,) studied this question.