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Enhancement of efficiencies of the cellular uptake and gene silencing of chitosan/siRNA complexes via the inclusion of a negatively charged poly(γ-glutamic acid)

Paper ID Volume ID Publish Year Pages File Format Full-Text
8863 608 2010 9 PDF Available
Title
Enhancement of efficiencies of the cellular uptake and gene silencing of chitosan/siRNA complexes via the inclusion of a negatively charged poly(γ-glutamic acid)
Abstract

Although advantageous for siRNA packing and protection, chitosan (CS)-based complexes may lead to difficulties in siRNA release once they arrive at the site of action, due to their electrostatic interactions. To assist the intracellular release of siRNA and thus enhance its effectiveness in gene silencing, we incorporated a negatively charged poly(γ-glutamic acid) (γ-PGA) into CS/siRNA complexes. The inclusion of γ-PGA did not alter the complex-formation ability between CS and siRNA; additionally, their cellular uptake was significantly enhanced. The results obtained in our molecular dynamic simulations indicate that the binding between CS and siRNA remained stable in the cytosol environment. In contrast, the compact structure of the ternary CS/siRNA/γ-PGA complexes was unpacked; such a structural unpackage may facilitate the intracellular release of siRNA. In the gene silencing study, we found that the inclusion of γ-PGA into complexes could significantly expedite the onset of gene knockdown, enhance their inhibition efficiency and prolong the duration of gene silencing. These findings may be attributed to the fact that there were significantly more CS/siRNA/γ-PGA complexes internalized into the cells in company with their more rapid intracellular unpackage and release of siRNA when compared with their binary counterparts in the absence of γ-PGA. The aforementioned results suggest that CS/siRNA/γ-PGA complexes can be an efficient vector for siRNA transfection.

Keywords
Chitosan; Small interfering RNA; Poly(γ-glutamic acid); Transfection; Gene silencing
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Enhancement of efficiencies of the cellular uptake and gene silencing of chitosan/siRNA complexes via the inclusion of a negatively charged poly(γ-glutamic acid)
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 31, Issue 33, November 2010, Pages 8780–8788
Authors
, , , , , ,
Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us