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

Centre de Recherches de Biochimie Macromoléculaire, CRBM-CNRS, Department of Molecular Biophysics and Therapeutics, 1919 Route de Mende, 34293 Montpellier, 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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    • "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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    ABSTRACT: Soon after discovery of RNA interference (RNAi), its potential as eff ective antiviral therapy was recognized. Since then RNAi has been variously exploited for antiviral purposes which could eff ectively block viral replication in vitro. For in vivo use, however, delivery issue, toxicity, RNAi suppression and viral escape are still major hurdles. Here, we provide an overview of the RNAi strategy and review the approaches that have been developed to surpass the obstacles and to achieve targeted gene silencing for antiviral and other therapies.
    01/2013; 18(1-2):1-23. DOI:10.17525/vrr.v18i1-2.92
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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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    ABSTRACT: The cell membrane is a highly selective barrier. This limits the cellular uptake of molecules including DNA, oligonucleotides, peptides and proteins used as therapeutic agents. Different approaches have been employed to increase the membrane permeability and intracellular delivery of these therapeutic molecules. One such approach is the use of Cell Penetrating Peptides (CPPs). CPPs represent a new and innovative concept, which bypasses the problem of bioavailability of drugs. The success of CPPs lies in their ability to unlock intracellular and even intranuclear targets for the delivery of agents ranging from peptides to antibodies and drug-loaded nanoparticles. This review highlights the development of cell penetrating peptides for cell-specific delivery strategies involving biomolecules that can be triggered spatially and temporally within a cell transport pathway by change in physiological conditions. The review also discusses conjugations of therapeutic agents to CPPs for enhanced intracellular delivery and bioavailability that are at the clinical stage of development.
    12/2012; 163(163). DOI:10.3390/biom2020187
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    • "To deliver miRNA into neural progenitor cells, a newly developed nanoparticle-mediated method was employed [24], To verify the delivery efficiency of nanoparticles, miR mimic indicator (cel-miR-67) which was conjugated with Dye548 was introduced into SVZ neural progenitor cells and approximately 90% progenitor cells were observed to be red fluorescence 10 h after delivery (Fig. 4A). However, no cell exhibited red fluorescence in the absence of nanoparticles, suggesting the specific and efficient delivery of miRNA into progenitor cells by nanoparticles (Fig. 4B). "
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    ABSTRACT: The Notch signaling pathway regulates adult neurogenesis under physiological and pathophysiological conditions. MicroRNAs are small non-coding RNA molecules that regulate gene expression. The present study investigated the effect of miR-124a on the Notch signaling pathway in stroke-induced neurogenesis. We found that adult rats subjected to focal cerebral ischemia exhibited substantial reduction of miR-124a expression, a neuron specific miRNA, in the neural progenitor cells of the subventricular zone (SVZ) of the lateral ventricle, which was inversely associated with activation of Notch signals. In vitro, transfection of neural progenitor cells harvested from the SVZ of adult rat with miR-124a repressed Jagged-1 (JAG1), a ligand of Notch, in a luciferase construct containing the JAG1 target site. Introduction of miR-124a in neural progenitor cells significantly reduced JAG1 transcript and protein levels, leading to inactivation of Notch signals. Transfection of neural progenitor cells with miR-124a significantly reduced progenitor cell proliferation and promoted neuronal differentiation measured by an increase in the number of Doublecortin positive cells, a marker of neuroblasts. Furthermore, introduction of miR-124a significantly increased p27Kip1 mRNA and protein levels, a downstream target gene of the Notch signaling pathway. Collectively, our study demonstrated that in vivo, stroke alters miRNA expression in SVZ neural progenitor cells and that in vitro, miR-124a mediates stroke-induced neurogenesis by targeting the JAG-Notch signaling pathway.
    PLoS ONE 08/2011; 6(8):e23461. DOI:10.1371/journal.pone.0023461 · 3.23 Impact Factor
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