RNA interference: a new alternative for rheumatic diseases therapy.
RNA interference (RNAi) is a post-transcriptional gene silencing mechanism preserved during evolution. This mechanism, recently described, is mediated by small double-stranded RNAs (dsRNAs) that can specifically recognize a target mRNA sequence and mediate its cleavage or translational repression. The use of RNAi as a tool for gene therapy has been extensively studied, especially in viral infections, cancer, inherited genetic disorders, cardiovascular and rheumatic diseases. Together with data from human genome, the knowledge of gene silencing mediated by RNAi could allow a functional determination of virtually any cell expressed gene and its involvement in cellular functioning and homeostasis. Several in vitro and in vivo therapeutic studies with autoimmune disease animal models have been carried out with promising results. The pathways of tolerance breakage and inflammation are potential targets for RNAi therapy in inflammatory autoimmune diseases. This review will present the basic principles of RNAi and discuss several aspects of RNAi-based therapeutic approaches, from in vitro tool design and target identification to in vivo pre-clinical drug delivery, and tests of autoimmune diseases in human cells and animal models. Finally, this review will present some recent clinical experience with RNAi-based therapy.
Rheumatology Division, UNIFESP, Brazil.
Natália Regine
NR
de França
Danilo
D
Mesquita Júnior
Amanda Bandeira
AB
Lima
Fernando Vianna Cabral
FV
Pucci
Luís Eduardo Coelho
LE
Andrade
Neusa Pereira
NP
Silva
D001327:Autoimmune Diseases / Q000235:genetics / Q000628:therapy; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D034622:RNA Interference; D012216:Rheumatic Diseases / Q000235:genetics* / Q000276:immunology / Q000628:therapy*