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Title: Dicer-labile PEG conjugates for siRNA delivery
Authors: Kow, Siew Ching
Mccorroll, Joshua A.
Valade, David
Boyer, Cyrille
Dwarte, Tanya
Davis, Thomas P.
Kavallaris, Maria
Bulmuş, Volga
Keywords: Antisense
Enhanced green fluorescent protein
Gel electrophoresis
Gene silencing
Human neuroblastoma
Addition reactions
siRNA delivery
Publisher: American Chemical Society
Source: Kow, S. C., McCarroll, J., Valade, D., Boyer, C., Dwarte, T., Davis, T. P., Kavallaris, M., and Bulmus, V. (2011). Dicer-labile PEG conjugates for siRNA delivery. Biomacromolecules, 12(12), 4301-4310. doi:10.1021/bm201199c
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.
ISSN: 1526-4602
Appears in Collections:Chemical Engineering / Kimya Mühendisliği
PubMed İndeksli Yayınlar Koleksiyonu / PubMed Indexed Publications Collection
Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection
WoS İndeksli Yayınlar Koleksiyonu / WoS Indexed Publications Collection

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