RNAi therapeutics: Principles, prospects and challenges

Abstract

RNA interference (RNAi) was discovered less than a decade ago and already there are human clinical trials in progress or planned. A major advantage of RNAi versus other anti-sense based approaches for therapeutic applications is that it utilizes cellular machinery that efficiently allows targeting of complementary transcripts, often resulting in highly potent down-regulation of gene expression. Despite the excitement about this remarkable biological process for sequence specific gene regulation, there are a number of hurdles and concerns that must be overcome prior to making RNAi a real therapeutic modality, which include off-target effects, triggering of type I interferon responses, and effective delivery in vivo. This review discusses mechanistic aspects of RNAi, the potential problem areas and solutions and therapeutic applications. It is anticipated that RNAi will be a major therapeutic modality within the next several years, and clearly warrants intense investigation to fully understand the mechanisms involved.

A Short Hairpin DNA Analogous to miR-125b Inhibits C-Raf Expression, Proliferation, and Survival of Breast Cancer Cells

“…These molecules exert different functions. SiRNA and asDNA primarily lead to reduction of mRNA by cleavage, whereas miRs primarily block translation (11)(12)(13). Inhibition of translation has also been described for asDNA as secondary effect (14,15).…”

Biomateriais para formulações de base nanotecnológica visando terapia gênica ocular

“…11,15 Têm como característica a presença de nucleotídeos 3' que podem ser reconhecidos pelo complexo de silenciamento induzido por RNA (RNA-induced silencing complex -RISC), o que resulta na degradação do mRNA homólogo. 16 Da mesma forma que AS--ON, os siRNA têm sido utilizados para diminuir a expressão de determinada proteína por um processo de nocaute (knock-down), também chamado de "silenciamento". Assim como os AS-ON, podem ser obtidos por síntese orgânica.…”

Interactions between the estrogen receptor, its cofactors and microRNAs in breast cancer

“…Whether miRNA-based RNAi therapeutics will develop at similar speed to siRNA therapeutics [69,70] remain to be seen. The challenges to development of siRNA-based therapeutics such as stable delivery and specificity of action [69,[71][72][73] will be revisited in the development of miRNA-based therapeutics. If these challenges can be overcome, miRNA-based therapeutics are likely to develop rapidly.…”