Strategies for the Delivery of Oligonucleotides in vivo

Reinsch, Christian; Siepi, Evgenios; Dieckmann, Andreas; Panzner, Steffen

doi:10.1039/9781847558275-00226

Cited by 3 publications

(1 citation statement)

References 57 publications

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“…A major practical limitation of these anionic liposomes, however, is their limited ability to encapsulate ONs due to a lack of electrostatic interaction (6,7). Cationic liposomes can effectively sequester ONs, but they also display unspecific binding to serum components or endothelia (8)(9)(10). We recently demonstrated that both efficient loading of ON and high biocompatibility can be achieved with the use of amphoteric liposomes (11).…”

Section: Introductionmentioning

confidence: 99%

An Ion Switch Regulates Fusion of Charged Membranes

Siepi¹,

Lutz²,

Meyer

et al. 2011

Biophysical Journal

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Here we identify the recruitment of solvent ions to lipid membranes as the dominant regulator of lipid phase behavior. Our data demonstrate that binding of counterions to charged lipids promotes the formation of lamellar membranes, whereas their absence can induce fusion. The mechanism applies to anionic and cationic liposomes, as well as the recently introduced amphoteric liposomes. In the latter, an additional pH-dependent lipid salt formation between anionic and cationic lipids must occur, as indicated by the depletion of membrane-bound ions in a zone around pH 5. Amphoteric liposomes fuse under these conditions but form lamellar structures at both lower and higher pH values. The integration of these observations into the classic lipid shape theory yielded a quantitative link between lipid and solvent composition and the physical state of the lipid assembly. The key parameter of the new model, κ(pH), describes the membrane phase behavior of charged membranes in response to their ion loading in a quantitative way.

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Section: Introductionmentioning

confidence: 99%

An Ion Switch Regulates Fusion of Charged Membranes

Siepi¹,

Lutz²,

Meyer

et al. 2011

Biophysical Journal

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RNA‐Interferenz: von den Grundlagen zur therapeutischen Anwendung

Kurreck

2009

Angewandte Chemie

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Ein effizienter Mechanismus zur sequenzspezifischen Inhibition einer Genexpression ist die RNA‐Interferenz. Hierbei führen doppelsträngige RNA‐Moleküle zur Spaltung der ausgewählten Ziel‐RNA (siehe Bild). Diese Technik hat sich in den vergangenen Jahren zu einer Standardmethode der Molekularbiologie entwickelt, die nach erfolgreichen Anwendungen im Tiermodell bereits in klinischen Studien als neue Therapieform erprobt wird. Vor gerade einmal zehn Jahren konnten Andrew Fire und Craig Mello zeigen, dass doppelsträngige RNA‐Moleküle in Eukaryoten die Expression homologer Gene posttranskriptionell inhibieren können. Dieser als RNA‐Interferenz bezeichnete Prozess hat sich mittlerweile zu einer Standardmethode der Molekularbiologie entwickelt. Der vorliegende Aufsatz gibt einen Überblick über die zugrunde liegenden zellulären Vorgänge mit besonderem Fokus auf die posttranskriptionelle Inhibition der Genexpression in Säugerzellen, die Anwendungsmöglichkeiten in der Forschung und die ersten Ergebnisse der bereits laufenden klinischen Studien.

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RNA Interference: From Basic Research to Therapeutic Applications

2009

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An efficient mechanism for the sequence-specific inhibition of gene expression is RNA interference. In this process, double-stranded RNA molecules induce cleavage of a selected target RNA (see picture). This technique has in recent years developed into a standard method of molecular biology. Successful applications in animal models have already led to the initiation of RNAi-based clinical trials as a new therapeutic option.Only ten years ago Andrew Fire and Craig Mello were able to show that double-stranded RNA molecules could inhibit the expression of homologous genes in eukaryotes. This process, termed RNA interference, has developed into a standard method of molecular biology. This Review provides an overview of the molecular processes involved, with a particular focus on the posttranscriptional inhibition of gene expression in mammalian cells, the possible applications in research, and the results of the first clinical studies.

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Strategies for the Delivery of Oligonucleotides in vivo

Cited by 3 publications

References 57 publications

An Ion Switch Regulates Fusion of Charged Membranes

An Ion Switch Regulates Fusion of Charged Membranes

RNA‐Interferenz: von den Grundlagen zur therapeutischen Anwendung

RNA Interference: From Basic Research to Therapeutic Applications

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