Abstract
RNA interference (RNAi) is a phenomenon of sequence-specific gene silencing in mammalian cells and its discovery has lead to its wide application as a powerful tool in post-genomic research. Recently, 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. Selection of appropriate gene targets is an important parameter in the potential success of siRNA cancer therapies. Candidate targets include genes associated with cell proliferation, metastasis, angiogenesis, and drug resistance. Importantly, silencing of such genes must not affect the functions of normal cells. Development of suitable drug delivery systems (DDSs) is also an important issue. Numerous methods to transfect siRNAs into cells have been developed, and the use of non-viral DDSs is preferred because it offers greater safety for clinical application than does the use of viral DDSs. Currently, atelocollagen and cationic liposomes represent the most advantageous non-viral DDSs available. In this article, we briefly review the mechanism of RNAi and non-viral DDSs. Next we discuss in detail some of the most recent findings concerning the administration of potential nucleic acid-based drugs against polo-like kinase-1 (PLK-1), which regulates the mitotic process in mammalian cells. These promising results demonstrate that PLK-1 is a suitable target for cancer therapy. Finally, several current clinical trials of RNAi therapies against cancers are discussed. Results of current studies and clinical trials demonstrate that manipulation of RNAi mechanism by use of targeted siRNA offers promising strategies for cancer therapies.
Keywords: RNAi, siRNA, cancer, PLK-1, DDS, liposome, atelocollagen
Current Drug Targets
Title: Future Prospect of RNA Interference for Cancer Therapies
Volume: 11 Issue: 3
Author(s): Eishi Ashihara, Eri Kawata and Taira Maekawa
Affiliation:
Keywords: RNAi, siRNA, cancer, PLK-1, DDS, liposome, atelocollagen
Abstract: RNA interference (RNAi) is a phenomenon of sequence-specific gene silencing in mammalian cells and its discovery has lead to its wide application as a powerful tool in post-genomic research. Recently, 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. Selection of appropriate gene targets is an important parameter in the potential success of siRNA cancer therapies. Candidate targets include genes associated with cell proliferation, metastasis, angiogenesis, and drug resistance. Importantly, silencing of such genes must not affect the functions of normal cells. Development of suitable drug delivery systems (DDSs) is also an important issue. Numerous methods to transfect siRNAs into cells have been developed, and the use of non-viral DDSs is preferred because it offers greater safety for clinical application than does the use of viral DDSs. Currently, atelocollagen and cationic liposomes represent the most advantageous non-viral DDSs available. In this article, we briefly review the mechanism of RNAi and non-viral DDSs. Next we discuss in detail some of the most recent findings concerning the administration of potential nucleic acid-based drugs against polo-like kinase-1 (PLK-1), which regulates the mitotic process in mammalian cells. These promising results demonstrate that PLK-1 is a suitable target for cancer therapy. Finally, several current clinical trials of RNAi therapies against cancers are discussed. Results of current studies and clinical trials demonstrate that manipulation of RNAi mechanism by use of targeted siRNA offers promising strategies for cancer therapies.
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Cite this article as:
Ashihara Eishi, Kawata Eri and Maekawa Taira, Future Prospect of RNA Interference for Cancer Therapies, Current Drug Targets 2010; 11 (3) . https://dx.doi.org/10.2174/138945010790711897
DOI https://dx.doi.org/10.2174/138945010790711897 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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