Advances in cancer gene therapy: tumor-targeted delivery of therapeutic pDNA, siRNA, and dsRNA nucleic acids.
Nonviral gene delivery systems are attractive because of their simplicity. One component (a natural or synthetic piece of nucleic acid) or two components (lipoplexes or polyplexes consisting of nucleic acid formulated with one cationic agent) may be sufficient. The simple design however entails also their limitation - a far lower efficiency than viral vectors, and lack of targeting specificity. First versions of more sophisticated "synthetic viruses" for plasmid DNA (pDNA), small interference RNA (siRNA), and dsRNA delivery have come into existence, and encouraging therapeutic effects in mouse tumor models have been observed. The development into pre-programmed bioresponsive systems, containing targeting ligands and shielding elements, and membrane-active modules promoting intracellular release is a fundamental part of the optimization process. Generation of better defined, biocompatible polymers will be an additional key aspect for successful clinical development of anticancer nucleic acid therapies.
Wagner
Ernst
E
Pharmaceutical Biotechnology and Center of NanoScience, Ludwig-Maximilians Universität, Munich, Germany. ernst.wagner@cup.uni-muenchen.de
D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D015972:Gene Expression Regulation, Neoplastic; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods* / Q000639:trends; D006801:Humans; D008024:Ligands; D051379:Mice; D036103:Nanotechnology; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D010957:Plasmids / Q000378:metabolism*; D011108:Polymers / Q000737:chemistry; D012330:RNA, Double-Stranded / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism
D001672:Biocompatible Materials; D008024:Ligands; D011108:Polymers; D012330:RNA, Double-Stranded; D034741:RNA, Small Interfering; D011956:Receptors, Cell Surface