siRNA-mediated antitumorigenesis for drug target validation and therapeutics.
Application of siRNA to knockdown a specific gene requires target mRNA accessibility, effective intracellular delivery of siRNA into target cells and potent siRNA inhibition of target mRNA. Use of siRNA as a tool is advancing in almost every field of biomedical research, but some of the most dynamic and exciting applications of siRNA are in cancer research. This review summarizes the results obtained with siRNA in cancer, in particular functional validation of tumorigenic genes in cell culture and animal tumor models, effective siRNA delivery systems, efficiency of siRNA agents compared with antisense oligonucleotides and efforts for potential therapeutic development. Along with the rapidly growing literature on using siRNA as a functional genomic tool, there is emerging evidence that siRNA may represent a novel therapeutic modality for cancer treatment when optimized local and systemic delivery systems are available.
Lu
Patrick Y
PY
Intradigm Corporation, 12115 K Parklawn Drive, Rockville, MD 20852, USA. patricklu@intradigm.com
Xie
Frank Y
FY
Woodle
Martin C
MC
D000818:Animals; D002453:Cell Cycle / Q000502:physiology; D020868:Gene Silencing; D018390:Gene Targeting; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D006133:Growth Substances / Q000378:metabolism; D009369:Neoplasms / Q000503:physiopathology / Q000628:therapy*; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D006133:Growth Substances; D016376:Oligonucleotides, Antisense; D034741:RNA, Small Interfering; D016159:Tumor Suppressor Protein p53; D011494:Protein Kinases