PEGylated poly(ethylene imine) copolymer-delivered siRNA inhibits HIV replication in vitro

Weber, Nick; Merkel, Olivia M.; Kissel, Thomas; Muñoz‐Fernández, María Ángeles

doi:10.1016/j.jconrel.2011.09.059

Cited by 43 publications

(19 citation statements)

References 33 publications

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“…Ten milligrams of POPC stock solution was dried under a rotary evaporator and stored under vacuum overnight to completely remove trace amounts of organic solvents. The dried lipid film was suspended in 1 ml of PBS (pH 7.2), and the resulting multilamellar vesicle suspension was freeze-thawed 6 times and then filtered through 2 stacked polycarbonate filters (0.1 m) 21 times using an Avanti miniextruder to (3). All three have a TBDPS group derived from the base site; however, structures 1 and 2 were analogous to nucleotide dT and differ from each other in the linker length of the TBDPS group, and structure 3 was analogous to nucleotide dA.…”

Section: Methodsmentioning

confidence: 99%

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DNA Duplexes with Hydrophobic Modifications Inhibit Fusion between HIV-1 and Cell Membranes

Xu¹,

Cai²,

Chen

et al. 2013

Antimicrob Agents Chemother

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Discovery of new drugs for the treatment of AIDS typically possessing unique structures associated with novel mechanisms of action has been of great importance due to the quick drug-resistant mutations of HIV-1 strains. The work presented in this report describes a novel class of DNA duplex-based HIV-1 fusion inhibitors. Hydrophobic groups were introduced into a DNA duplex skeleton either at one end, at both ends, or in the middle. These modified DNA duplexes inhibited fusion between HIV-1 and human cell membranes at micro-or submicromolar concentrations. Respective inhibitors adopted an aptamer pattern instead of a base-pairing interaction pattern. Structure-activity relationship studies of the respective DNA duplexes showed that the rigid and negatively charged DNA skeletons, in addition to the presence of hydrophobic groups, were crucial to the anti-HIV-1 activity of these compounds. A fluorescent resonance energy transfer (FRET)-based inhibitory assay showed that these duplex inhibitors interacted with the primary pocket in the gp41 N-terminal heptad repeat (NHR) instead of interacting with the lipid bilayers.

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Section: Methodsmentioning

confidence: 99%

“…Oligonucleotides represent a category of anti-HIV-1 drug candidates, including small interfering RNA (siRNA) and antisense oligonucleotides that specifically interact with target genes via complementary base pairing (2)(3)(4)(5). Interestingly, some sequences do not act through base pairing but as aptamers.…”

mentioning

confidence: 99%

DNA Duplexes with Hydrophobic Modifications Inhibit Fusion between HIV-1 and Cell Membranes

Xu¹,

Cai²,

Chen

et al. 2013

Antimicrob Agents Chemother

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show abstract

“…Shielding of cationic charge of transfection agents by inert hydrophilic polymers such as polyethylene glycol (PEG) leads to a reduction of their toxicity [14], and protects polynucleic acids from degradation in the acidic milieu of the endosomes or lysosomes [15]. Furthermore the degradation products of the carrier should be sufficiently small (molecular weight < 20 kDa) to enable rapid removal by excretory organs like kidneys.…”

Section: Introductionmentioning

confidence: 99%

Cellular delivery of polynucleotides by cationic cyclodextrin polyrotaxanes

Dandekar

Jain

Keil

et al. 2012

Journal of Controlled Release

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Cationic polyrotaxanes, obtained by temperature activated threading of cationic cyclodextrin derivatives onto water soluble cationic polymers (ionenes), form metastable nanometric polyplexes with pDNA and combinations of siRNA with pDNA.Because of their low toxicity, the polyrotaxane polyplexes constitute a very interesting system for the transfection of polynucleotides into mammalian cells. The complexation of Cy3-labeled siRNA within the polyplexes was demonstrated by fluorescence correlation spectroscopy. The uptake of the polyplexes (red) was imaged by confocal fluorescence microscopy using the A549 cell line as a model (blue: nuclei, green: membranes). The results prove the potential of polyrotaxanes for further investigations involving knocking down genes of therapeutic interest.

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“…They synthesized complexes of nanoparticles made of polyethylene glycol-polyethyleneimine (PEG-PEI) loaded with siRNA against ROCK-II and transfected to C17.2 neural stem cells in vitro. PEI is one of the most successful polycationic carriers used for non-viral gene delivery (Huang et al, 2011), and hydrophilic PEG moieties were engrafted onto the PEI core to decrease its cytotoxicity and improve resistance to enzymatic degradation (Weber et al, 2012). From their results, they conclude that the complexes with the best characteristics (high transfection efficiency of 70% and low cytotoxicity -cell viability was 80%) were achieved with a charge ratio between the amino groups of PEG-PEI and phosphate groups of the siRNA (N/P ratio) of 50.…”

Section: Sirna Deliverymentioning

confidence: 99%

siRNA as a tool to improve the treatment of brain diseases: Mechanism, targets and delivery

Gomes¹,

Martins²,

Sarmento³

2015

Ageing Research Reviews

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PEGylated poly(ethylene imine) copolymer-delivered siRNA inhibits HIV replication in vitro

Cited by 43 publications

References 33 publications

DNA Duplexes with Hydrophobic Modifications Inhibit Fusion between HIV-1 and Cell Membranes

DNA Duplexes with Hydrophobic Modifications Inhibit Fusion between HIV-1 and Cell Membranes

Cellular delivery of polynucleotides by cationic cyclodextrin polyrotaxanes

siRNA as a tool to improve the treatment of brain diseases: Mechanism, targets and delivery

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