Sustained delivery of siRNAs targeting viral infection by cell-degradable multilayered polyelectrolyte films

Dimitrova, Maria; Affolter, Christine; Meyer, Florent; Nguyen, Isabelle; Richard, Daniel; Schuster, Catherine; Bartenschlager, Ralf; Voegel, Jean‐Claude; Ogier, Joëlle; Baumert, Thomas F.

doi:10.1073/pnas.0800156105

Cited by 68 publications

(60 citation statements)

References 26 publications

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“…[218,219] Recently, Dimitrova et al [219] demonstrated, using hepatitis C virus infection (HCV) as a model, that siRNAs targeting the viral genome were efficiently delivered by PEM films. This delivery method resulted in a marked, dosedependent, specific, and sustained inhibition of HCV replication and infection in hepatocyte-derived cells.…”

Section: Localized Gene Therapy Of Dna and Rnamentioning

confidence: 99%

Multiple Functionalities of Polyelectrolyte Multilayer Films: New Biomedical Applications

Boudou¹,

Crouzier²,

Ren³

et al. 2010

Advanced Materials

695

702

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The design of advanced functional materials with nanometer- and micrometer-scale control over their properties is of considerable interest for both fundamental and applied studies because of the many potential applications for these materials in the fields of biomedical materials, tissue engineering, and regenerative medicine. The layer-by-layer deposition technique introduced in the early 1990s by Decher, Moehwald, and Lvov is a versatile technique, which has attracted an increasing number of researchers in recent years due to its wide range of advantages for biomedical applications: ease of preparation under "mild" conditions compatible with physiological media, capability of incorporating bioactive molecules, extra-cellular matrix components and biopolymers in the films, tunable mechanical properties, and spatio-temporal control over film organization. The last few years have seen a significant increase in reports exploring the possibilities offered by diffusing molecules into films to control their internal structures or design "reservoirs," as well as control their mechanical properties. Such properties, associated with the chemical properties of films, are particularly important for designing biomedical devices that contain bioactive molecules. In this review, we highlight recent work on designing and controlling film properties at the nanometer and micrometer scales with a view to developing new biomaterial coatings, tissue engineered constructs that could mimic in vivo cellular microenvironments, and stem cell "niches."

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Section: Localized Gene Therapy Of Dna and Rnamentioning

confidence: 99%

Multiple Functionalities of Polyelectrolyte Multilayer Films: New Biomedical Applications

Boudou¹,

Crouzier²,

Ren³

et al. 2010

Advanced Materials

695

702

View full text Add to dashboard Cite

show abstract

“…PEI25K/siRNA complexes were prepared as described previously with slight modification. 36 Briefly, 10 μg of siRNAs was dissolved in 150 μl of 150 mM NaCl and incubated for 10 min. Thirty-three microliters of PEI25K (5 mg/ml) in 150 mM NaCl was added to the siRNA solution, resulting in a nitrogen-to-phosphorus (N/P) ratio of 33.…”

Section: Methodsmentioning

confidence: 99%

Silencing of ribonucleotide reductase subunit M1 potentiates the antitumor activity of gemcitabine in resistant cancer cells

Wonganan

Chung

Zhu

et al. 2012

Cancer Biology & Therapy

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“…Multilayered architectures have been shown to deliver drugs (26)(27)(28)(29) and DNA (30)(31)(32)(33)(34), but little is known about whether this technique is feasible for the sustained delivery of siRNAs. Dimitrova et al (2008) used multilayered polyelectrolyte films consisting of polylysine and polyglutamic acid as a precursor film and a hyaluronan-chitosan layer for the adsorption of PEI siRNA complexes that delivered siRNA to Huh7.5 cells (35). Interestingly, Neumann et al (2006) used a gelatin layer with Lipofectamine™ 2000 and siRNAs for high-throughput RNAi screening on microarray for mainly HeLa cells (36).…”

Section: Introductionmentioning

confidence: 99%

Small-Interfering RNA-Eluting Surfaces as a Novel Concept for Intravascular Local Gene Silencing

Nolte

Walker

Schneider

et al. 2011

Mol Med

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New drug-eluting stent (DES) methods have recently been demonstrated to improve outcomes of intravascular interventions.A novel technique is the design of gene-silencing stents that elute specific small-interfering RNAs (siRNAs) for better vascular wall regeneration. Although siRNAs used to alter gene expression have surpassed expectations in in vitro experiments, the functional and local delivery of siRNAs is still the major obstacle for the in vivo application of RNA interference. In this preliminary in vitro study we investigated a surface-immobilized siRNA delivery technique that would be readily adaptable for local intravascular applications in vivo. The transfection potency of gelatin coatings consisting of a specific siRNA complexed with polyethylenimine (PEI) was examined in primary human endothelial cells by flow cytometry and quantitative real-time polymerase chain reaction. Several media conditions, such as the presence or absence of serum during cultivation, were investigated. Furthermore, different siRNA and PEI amounts, as well as nitrogen/phosphate ratios, were tested for their transfection efficiency. Gelatin coatings consisting of PEI and siRNA against an exemplary endothelial adhesion molecule receptor achieved a significant knockdown of around 70%. The transfection efficiency of the coatings was not influenced by the presence of serum. The results of this preliminary study support the expectation that this novel coating may be favorable for local in vivo gene silencing (for example, when immobilized on stents or balloons for percutanous transluminal coronary angioplasty). However, further animal experiments are needed to confirm the translation into clinical practice. This intriguing technology leads the way to more sophisticated and individualized coatings for the post-DES era, toward silencing of genes involved in the pathway of intimal hyperplasia.

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Sustained delivery of siRNAs targeting viral infection by cell-degradable multilayered polyelectrolyte films

Abstract: RNAi ͉ therapy ͉ hepatitis C virus ͉ hepatocyte ͉ liver

Cited by 68 publications

References 26 publications

Multiple Functionalities of Polyelectrolyte Multilayer Films: New Biomedical Applications

Multiple Functionalities of Polyelectrolyte Multilayer Films: New Biomedical Applications

Silencing of ribonucleotide reductase subunit M1 potentiates the antitumor activity of gemcitabine in resistant cancer cells

Small-Interfering RNA-Eluting Surfaces as a Novel Concept for Intravascular Local Gene Silencing

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