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Nanomedicine. 2009 Mar;5(1):8-20. doi: 10.1016/j.nano.2008.06.001. Epub 2008 Jul 18.

Drug delivery of siRNA therapeutics: potentials and limits of nanosystems.

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Institute of Pharmaceutical Sciences, Department of Pharmaceutical Technology, Karl-Franzens-University, Graz, Austria.


Gene therapy is a promising tool for the treatment of human diseases that cannot be cured by rational therapies. The major limitation for the use of small interfering RNA (siRNA), both in vitro and in vivo, is the inability of naked siRNA to passively diffuse through cellular membranes due to the strong anionic charge of the phosphate backbone and consequent electrostatic repulsion from the anionic cell membrane surface. Therefore, the primary success of siRNA applications depends on suitable vectors to deliver therapeutic genes. Cellular entrance is further limited by the size of the applied siRNA molecule. Multiple delivery pathways, both viral and nonviral, have been developed to bypass these problems and have been successfully used to gain access to the intracellular environment in vitro and in vivo, and to induce RNA interference (RNAi). This review focuses on different pathways for siRNA delivery and summarizes recent progress made in the use of vector-based siRNA technology.

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