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- W588449341 abstract "RNA interference (RNAi) provides a specific and efficient way to silence gene expression;therefore, it is an attractive tool to be used in basic research on gene function as well asgene therapy. Despite the enormous potential of RNAi, delivering the small interferingRNA (siRNA) to the cells is one of the main hurdles. Previously there have been reportsshowing effective plasmid DNA delivery to cells and such systems could be used to deliversiRNA to cells due to the similarity of the delivery criteria between plasmid DNA andsiRNA. Therefore, I hypothesise that a successful siRNA delivery system will have similarbiophysical characteristics as a successful DNA delivery system. The aim of this study is toidentify the important criteria to establish a promising siRNA delivery system bycomparing the criteria of successful DNA delivery systems such as linear and branchedpolylysines and linear and branched PEIs.In order to deliver nucleic acid to a cell, a vector system should be able to bind and form apositively surface-charged nano-sized complex with the nucleic acid for cellular bindingand uptake. Inside the cell, the vector should be able to dissociate from the nucleic acid forgene expression or silencing. Therefore, the important parameters to investigate are thebinding and dissociation properties of the vector components to the nucleic acid and thesize and surface charge of the complex. From the results, generally all the polylysines andPEIs can bind, dissociate and form a positively charged nano-particle with plasmid DNA,which can mediate gene expression. Despite the ability of all the polylysines and PEIs tobind to and dissociate from siRNA, only branched polylysines, linear and branched PEI, but not linear polylysines can form positively charged nano-particles with siRNA. Indeed,branched PEI behaves similarly towards siRNA and DNA biophysically. Interestingly, onlybranched PEI and siRNA complexes can mediate cellular uptake and 60% target geneknockdown. Branched polylysines or linear PEI siRNA complexes cannot mediate genesilencing in spite of the formation of positively charged nano-particles. This could be due topoor cellular uptake of these complexes or degradation of siRNA upon uptake. Therefore,to improve the design of the siRNA vector system, there is a need to research the cellularbinding and uptake of siRNA complexes in the future." @default.
- W588449341 created "2016-06-24" @default.
- W588449341 creator A5041495304 @default.
- W588449341 date "2009-08-01" @default.
- W588449341 modified "2023-09-24" @default.
- W588449341 title "A comparative study of cationic formulations for the delivery of siRNA and DNA" @default.
- W588449341 hasPublicationYear "2009" @default.
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