2007
DOI: 10.2174/156802607780487704
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Chemical Modifications to Improve the Cellular Uptake of Oligonucleotides

Abstract: Specific control of gene expression by synthetic oligonucleotides (ON) is now widely used for target validation but clinical applications are limited by ON bioavailability. Moreover, most currently used strategies for physical and chemical delivery cannot be easily implemented in vivo. This article reviews new strategies which appear promising for ON delivery. The first part deals with ON chemical modifications aiming at improving cellular uptake as for instance the grafting of cationic groups on the ON backbo… Show more

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Cited by 49 publications
(26 citation statements)
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“…S1-S7). This is consistent with reports that show that endosomal release of CPP-cargo conjugates is sometimes very inefficient, one factor that currently limits their utility for macromolecular cargo delivery (19,25,29,30). Another factor that can limit the utility of cationic CPPs is that they do not enter cells that are not capable of endocytosis.…”
Section: Discussionsupporting
confidence: 90%
See 1 more Smart Citation
“…S1-S7). This is consistent with reports that show that endosomal release of CPP-cargo conjugates is sometimes very inefficient, one factor that currently limits their utility for macromolecular cargo delivery (19,25,29,30). Another factor that can limit the utility of cationic CPPs is that they do not enter cells that are not capable of endocytosis.…”
Section: Discussionsupporting
confidence: 90%
“…Once endocytosed, there is the complicating question of cargo release from endosomes that has sometimes been attributed to spontaneous membrane translocation (16). As we show below, endosomal release can be very inefficient (19,25,29,30) and can effectively prevent the delivery of some endocytosed cargos to the cytosol. Given this roadblock to delivery, various approaches based on physical or osmotic lysis of endosomes have been tested to increase the efficiency of endosomal release postuptake (22,29,(31)(32)(33)(34).…”
mentioning
confidence: 82%
“…Chemical modifications have been found to reduce the immune stimulatory capability of RNA duplexes (Morrissey et al 2005;Behlke 2008;Judge and MacLachlan 2008;Watts et al 2008;Robbins et al 2009). Chemical modifications have also been developed to improve pharmacological properties of siRNAs, including stability against nucleases found in biological fluids and improved cellular uptake (Bumcrot et al 2006;Debart et al 2007).…”
Section: Introductionmentioning
confidence: 99%
“…The combination of nucleotides with aminoalkyl chains greatly enhances the variety of possible structures as well as their potential application [24]. Thus, oligonucleotides possessing cationic functionalities in addition to the anionic phosphate backbone have been shown to exhibit promising properties [25][26][27][28]. Polyamines, putrescine, spermine and spermidine, are involved in the regulation of gene function [29,30].…”
Section: Introductionmentioning
confidence: 99%