Dicer-Labile PEG Conjugates for siRNA Delivery

Kow, Siew Ching, McCarroll, Josh, Valade, David, Boyer, Cyrille, Dwarte, Tanya, Davis, Thomas P., Kavallaris, Maria and Bulmus, Volga (2011) Dicer-Labile PEG Conjugates for siRNA Delivery. Biomacromolecules, 12 12: 4301-4310. doi:10.1021/bm201199c


Author Kow, Siew Ching
McCarroll, Josh
Valade, David
Boyer, Cyrille
Dwarte, Tanya
Davis, Thomas P.
Kavallaris, Maria
Bulmus, Volga
Title Dicer-Labile PEG Conjugates for siRNA Delivery
Journal name Biomacromolecules   Check publisher's open access policy
ISSN 1525-7797
1526-4602
Publication date 2011-12
Sub-type Article (original research)
DOI 10.1021/bm201199c
Volume 12
Issue 12
Start page 4301
End page 4310
Total pages 10
Place of publication Washington, DC, United States
Publisher American Chemical Society
Collection year 2012
Language eng
Formatted abstract
Poly(ethylene glycol) (PEG) conjugates of Dicer-substrate small interfering RNA (DsiRNA) have been prepared to investigate a new siRNA release strategy. 3'-sense or 5'-antisense thiol-modified, blunt-ended DsiRNAs, inhibiting enhanced green fluorescent protein (eGFP) expression, were covalently conjugated to PEG with varying molecular weights (2, 10, and 20 kg/mol) through a stable thioether bond using a Michael addition reaction. The DsiRNA conjugates with 2 kg/mol PEG (both 3'-sense or 5'-antisense strand conjugated) and the 10 kg/mol PEG conjugated to the 3'-sense strand of DsiRNA were efficiently cleaved by recombinant human Dicer to 21-mer siRNA, as determined by gel electrophoresis. Importantly, 2 and 10 kg/mol PEG conjugated to the 3'-sense strand of DsiRNA showed potent gene silencing activity in human neuroblastoma (SH-EP) cells, stably expressing eGFP, at both the mRNA and protein levels. Moreover, the 10 kg/mol PEG conjugates of the 3'-sense strand of DsiRNA were less immunogenic when compared with the unmodified DsiRNA, determined via an immune stimulation assay on human peripheral blood mononuclear cells.
Keyword Polyelectrolyte Complex Micelles
Double-Stranded-Rna
Poly(ethylene Glycol)-Sirna Conjugate
In-Vivo Delivery
Vegf Sirna
Pegylated Polyplexes
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status Non-UQ
Additional Notes Published: November 4, 2011

Document type: Journal Article
Sub-type: Article (original research)
Collections: Non HERDC
Australian Institute for Bioengineering and Nanotechnology Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 15 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 15 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Sun, 08 Jan 2012, 08:09:45 EST by System User on behalf of Aust Institute for Bioengineering & Nanotechnology