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RNAi in therapy

100%

Kubiak K. , Nawrot B.

2009

nr 1

132-151

The discovery of RNA interference caused a revival of the concept of short nucleic acids application as molecular tools for therapeutic control of gene expression. After almost a decade of intensive research by leading pharmaceutical companies, there is only a limited number of clinical trials of synthetic siRNAs. In this review, we shall summarize the present status of knowledge of RNAi mechanism of action and discuss the potential of the use of siRNA in theraphy. We shall also provide data on recent achievements in current clinical trials based on RNAi techniques.

RNA interference-based therapeutics in anticancer therapy

100%

Kaminska B. , Kulesza D. , Wisniewski P.

Biotechnologia

2010

nr 3

94-114

RNA interference (RNAi) is a phenomenon of sequence-specific gene silencing and its discovery led to wide applications. Short interfering RNA (siRNA), which induces RNAi, has been experimentally introduced as a cancer therapy and is expected to be developed as a nucleic acid-based medicine. Potential success of siRNA cancer therapies depends on selection of appropriate gene targets and candidate targets include genes associated with cell proliferation, metastasis, angiogenesis, and drug resistance. In vivo systemic delivery of siRNA-based therapeutics to tumour tissues is challenging and the major limitations of siRNA therapeutic use are its degradation by serum nucleases, poor cellular uptake and rapid renal clearance following systemic administration. Several siRNA-based therapeutics are already in clinical trials. Further development of anti-cancer therapeutic siRNAs depends on development of nanocarriers, nuclease-resistant chemically modified siRNAs and variety of synthetic or natural lipids and polymers to systemically deliver siRNA. Here, we review potential approaches for delivery of RNAi based therapeutic in cancer therapy, results of current studies and clinical trials which demonstrate that the use of targeted siRNA offers promising strategies for cancer therapies.

RNA interference ? significance and applications

100%

Stanislawska J. , Olszewski W. L.

Archivum Immunologiae et Therapiae Experimentalis

2005

tom 53

nr 1

39-46

RNA interference (RNAi) is a post-transcriptional, highly conserved process in eukaryotes that leads to specific gene silencing through degradation of the target mRNA. This mechanism is mediated by double-stranded RNA (dsRNA) that is homologous in sequence to the silenced gene. The dsRNA is processed into small interfering RNA (siRNA) by an enzyme called Dicer, and the siRNAs are then incorporated into a multi-component RNA- -induced silencing complex, which finds and cleaves the target mRNA. In plants and worms, amplification of the silencing signal and cell-to-cell RNAi spreading is observed. The proposed biological roles of RNAi include resistance to viruses, transposons (mainly in plants), and the silencing and regulation of gene expression, particularly during development. In developmental gene control, specific small RNAs (micro RNA and small temporal RNA) are involved, which are processed in the same way as dsRNAs but act at the level of translation. RNAi technology has become a powerful tool in functional genomic analyses and may prove to be a useful method to develop highly specific gene-silencing therapeutics against viral infections and cancer in the future.