Abstract
The potential to control and alter gene expression constitutes an essential strategy in both fundamental and pharmaceutical research. The recent discovery of the RNA interference pathway in a wide variety of eukaryotic organisms has provided a novel means of characterizing gene function in mammalian cells and new perspectives in both molecular biology and future therapeutic developments (1–3). Short, interfering RNAs (siRNAs) constitute a powerful tool to silence gene expression posttranscriptionally (1–3). However, the major limitation of siRNA application, as for most antisense or nucleic acid-based strategies, remains their poor cellular uptake associated with low permeability of the cell membrane to nucleic acids (4,5). Several viral (6–9) and nonviral (6,10) strategies have been proposed to improve the delivery of either siRNAs expressing vectors or synthetic siRNAs, both in cultured cells and in vivo (6). So far, although siRNA transfection can be achieved with classical laboratory-cultured cell lines using lipid-based formulations, siRNA delivery remains a major challenge for many cell lines and there is still no reasonably efficient method for in vivo application (6). The most efficient method for in vivo applications is the nonviral “hydrodynamic” tail-vein injection of mice with high doses of siRNA (11–13). Cell-penetrating peptides are powerful carriers for cellular uptake of a variety of macromolecules, including proteins, peptides, and oligonucleotides (14–17). Several peptide-based strategies have been developed to improve the delivery of oligonucleotides both in vitro and in vivo using either covalent or complex approaches (18–20).
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Acknowledgments
This work was supported in part by the Centre National de la Recherche Scientifique (CNRS) and by grants from the Agence Nationale de Recherche sur le SIDA (ANRS), the European Community (QLK2-CT-2001-01451), the Association pour la Recherche sur le Cancer to M.C.M. (ARC-4326) and to G.D. (ARC-5271). F.S. was supported by a grant from La Ligue de Recherche Contre le Cancer.
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Simeoni, F., Morris, M.C., Heitz, F., Divita, G. (2005). Peptide-Based Strategy for siRNA Delivery into Mammalian Cells. In: Carmichael, G.G. (eds) RNA Silencing. Methods in Molecular Biology™, vol 309. Humana Press. https://doi.org/10.1385/1-59259-935-4:251
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DOI: https://doi.org/10.1385/1-59259-935-4:251
Publisher Name: Humana Press
Print ISBN: 978-1-58829-436-4
Online ISBN: 978-1-59259-935-6
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