Conjugation of siRNA with comb-type PEG enhances serum stability and gene silencing efficiency

Karthikeyan Gunasekaran; Thi Hoa Tam Nguyen; Heather D Maynard; Thomas Paul Davis; Volga Bulmus

doi:10.1002/marc.201000804

Conjugation of siRNA with comb-type PEG enhances serum stability and gene silencing efficiency

Karthikeyan Gunasekaran, Thi Hoa Tam Nguyen, Heather D Maynard, Thomas Paul Davis, Volga Bulmus

Research output: Contribution to journal › Article › Research › peer-review

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Abstract

A thiol-modified siRNA targeting the enhanced green fluorescence protein (eGFP) gene was conjugated with RAFT-synthesized, pyridyl disulfide-functional poly(PEG methyl ether acrylate)s (p(PEGA)s). siRNA-p(PEGA) conjugates demonstrated significantly enhanced in vitro serum stability and nuclease resistance compared to the unmodified and thiol-modified siRNA. The complexes of siRNA-p(PEGA) conjugates with a fusogenic peptide, KALA ((+)/(-) = 2) inhibited the protein expression approximately 28-fold more than the KALA complex of the unmodified siRNA. The protein inhibition caused by siRNA-p(PEGA)-KALA complexes (56? 5 -58? 3 of the fluorescence expressed in non-treated cells) was comparable to the effect of the unmodified siRNA-lipofectamine complex (77? 7 ).

Original language	English
Pages (from-to)	654 - 659
Number of pages	6
Journal	Macromolecular Rapid Communications
Volume	32
Issue number	8
DOIs	https://doi.org/10.1002/marc.201000804
Publication status	Published - 2011
Externally published	Yes

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title = "Conjugation of siRNA with comb-type PEG enhances serum stability and gene silencing efficiency",

abstract = "A thiol-modified siRNA targeting the enhanced green fluorescence protein (eGFP) gene was conjugated with RAFT-synthesized, pyridyl disulfide-functional poly(PEG methyl ether acrylate)s (p(PEGA)s). siRNA-p(PEGA) conjugates demonstrated significantly enhanced in vitro serum stability and nuclease resistance compared to the unmodified and thiol-modified siRNA. The complexes of siRNA-p(PEGA) conjugates with a fusogenic peptide, KALA ((+)/(-) = 2) inhibited the protein expression approximately 28-fold more than the KALA complex of the unmodified siRNA. The protein inhibition caused by siRNA-p(PEGA)-KALA complexes (56? 5 -58? 3 of the fluorescence expressed in non-treated cells) was comparable to the effect of the unmodified siRNA-lipofectamine complex (77? 7 ).",

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T1 - Conjugation of siRNA with comb-type PEG enhances serum stability and gene silencing efficiency

AU - Gunasekaran, Karthikeyan

AU - Nguyen, Thi Hoa Tam

AU - Maynard, Heather D

AU - Davis, Thomas Paul

AU - Bulmus, Volga

PY - 2011

Y1 - 2011

N2 - A thiol-modified siRNA targeting the enhanced green fluorescence protein (eGFP) gene was conjugated with RAFT-synthesized, pyridyl disulfide-functional poly(PEG methyl ether acrylate)s (p(PEGA)s). siRNA-p(PEGA) conjugates demonstrated significantly enhanced in vitro serum stability and nuclease resistance compared to the unmodified and thiol-modified siRNA. The complexes of siRNA-p(PEGA) conjugates with a fusogenic peptide, KALA ((+)/(-) = 2) inhibited the protein expression approximately 28-fold more than the KALA complex of the unmodified siRNA. The protein inhibition caused by siRNA-p(PEGA)-KALA complexes (56? 5 -58? 3 of the fluorescence expressed in non-treated cells) was comparable to the effect of the unmodified siRNA-lipofectamine complex (77? 7 ).

AB - A thiol-modified siRNA targeting the enhanced green fluorescence protein (eGFP) gene was conjugated with RAFT-synthesized, pyridyl disulfide-functional poly(PEG methyl ether acrylate)s (p(PEGA)s). siRNA-p(PEGA) conjugates demonstrated significantly enhanced in vitro serum stability and nuclease resistance compared to the unmodified and thiol-modified siRNA. The complexes of siRNA-p(PEGA) conjugates with a fusogenic peptide, KALA ((+)/(-) = 2) inhibited the protein expression approximately 28-fold more than the KALA complex of the unmodified siRNA. The protein inhibition caused by siRNA-p(PEGA)-KALA complexes (56? 5 -58? 3 of the fluorescence expressed in non-treated cells) was comparable to the effect of the unmodified siRNA-lipofectamine complex (77? 7 ).

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DO - 10.1002/marc.201000804

M3 - Article

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JO - Macromolecular Rapid Communications

JF - Macromolecular Rapid Communications

IS - 8

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Conjugation of siRNA with comb-type PEG enhances serum stability and gene silencing efficiency

Abstract

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