A non-covalent peptide-based strategy for siRNA delivery: Figure 1

French National Centre for Scientific Research, Lutetia Parisorum, Île-de-France, France
Biochemical Society Transactions (Impact Factor: 3.19). 03/2007; 35(Pt 1):44-6. DOI: 10.1042/BST0350044
Source: PubMed


The major obstacle to clinical development of siRNAs (short interfering RNAs), like for most of the nucleic-acid-based strategies, is their poor cellular uptake and bioavailability. Although several viral and non-viral strategies have been proposed to improve siRNA delivery, their applications in vivo remain a major challenge. We have developed a new strategy, based on a short amphipathic peptide, MPG, that is able to form stable nanoparticles with siRNA. MPG-based particles enter the cell independently of the endosomal pathway and can efficiently deliver siRNA in a fully biologically active form into a variety of cell lines and in vivo. This short review will discuss the mechanism and the potency of the MPG strategy for siRNA delivery both in vitro and in vivo.

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Available from: Laurence Crombez (Campion)
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    • "Studies by Simeoni and colleagues suggest MPG exhibits high affinity in the nanomolar range for siRNA and that approximately 10 to 20 peptide molecules are required to form a highly stable nanoparticle (Simeoni et al., 2003). The presence of a peptide-based nanostructure associated to the siRNA dramatically improved its stability inside the cell and significantly protected it from degradation (Crombez et al., 2007). The internalization process of MPG according to Deshayes et al. (2004) is achieved through formation of a carrier/cargo complex and occurs through a nonendosomal pathway leading to a mainly nuclear final localization of the cargo. "

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    • "Polyethyleneimines (PEI) are polycation-containing block copolymers (Muratovska & Eccles 2004), which have also been used for delivery of siRNA molecules in vivo, although PEI use in vivo has some toxicity issues (Crombez et al. 2009). Chitosan is a biodegradable, biocompatible and non-toxic cationic polymer obtained from deacetylation of chitin, which has been proposed as biocompatible alternative to cationic polymers, suitable for non-viral nucleic acid delivery (Crombez et al. 2007). Chitosans have been used for siRNA delivery in vitro as well as in vivo (Kumar et al. 2008). "
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    • "The covalent linkage of CPPs to siRNAs results in the formation of small, monomeric CPP/siRNA conjugates of known stoichiometry with high reproducibility [26]. CPPs could therefore be used for delivery of siRNAs either by covalent or non-covalent approaches [27]. However non-covalent strategies are more efficient for siRNA delivery, for example MPG peptide has been extensively reported to improve siRNA delivery into a large panel of cell lines including adherent cell lines, cells in suspension, cancer and challenging primary cell lines biological response [28,29]. "
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