Gene silencing efficiency of siRNA-PEG conjugates: Effect of PEGylation site and PEG molecular weight

Sooyeon Jung; Soo Hyeon Lee; Hyejung Mok; Hyun Jung Chung; Tae Gwan Park

doi:10.1016/j.jconrel.2010.03.002

Gene silencing efficiency of siRNA-PEG conjugates: Effect of PEGylation site and PEG molecular weight

Sooyeon Jung, Soo Hyeon Lee, Hyejung Mok, Hyun Jung Chung, Tae Gwan Park

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

72 Scopus citations

Abstract

Small interfering RNA (siRNA) was conjugated with poly(ethylene glycol) (PEG) at four different terminal ends (sense 3', sense 5', antisense 3', and antisense 5') via cleavable disulfide and noncleavable thioether linkages to evaluate their gene silencing efficiencies upon complexation with Lipofectamine™2000. The PEGylation site at the four siRNA termini and PEG molecular weight were not critical factors to significantly affect gene silencing activities. Cleavable siRNA-PEG conjugates showed comparable gene silencing activities to naked siRNA, and exhibited sequence-specific degradation of a target mRNA. Interestingly, noncleavable siRNA-PEG conjugates were processed by Dicer, enabling to exert RNAi effect without showing a target sequence-specific manner. However, only cleavable siRNA-PEG conjugates significantly reduced the extent of INF-α release as compared to noncleavable siRNA-PEG conjugates, suggesting that they can be potentially used for therapeutic siRNA applications.

Original language	English
Pages (from-to)	306-313
Number of pages	8
Journal	Journal of Controlled Release
Volume	144
Issue number	3
DOIs	https://doi.org/10.1016/j.jconrel.2010.03.002
State	Published - Jun 2010
Externally published	Yes

Funding

This study was supported by the Intelligent Drug Delivery System grant, A3 project, and World Class University program from the Ministry of Education, Science and Technology, Republic of Korea .

Funders	Funder number
Intelligent Drug Delivery System
Ministry of Education, Science and Technology

Keywords

Cleavable linkage
Conjugate site
Gene inhibition
PEGylation
SiRNA

Access to Document

10.1016/j.jconrel.2010.03.002

Cite this

@article{2fa796a7accb4747aa9561582ca69a03,

title = "Gene silencing efficiency of siRNA-PEG conjugates: Effect of PEGylation site and PEG molecular weight",

abstract = "Small interfering RNA (siRNA) was conjugated with poly(ethylene glycol) (PEG) at four different terminal ends (sense 3', sense 5', antisense 3', and antisense 5') via cleavable disulfide and noncleavable thioether linkages to evaluate their gene silencing efficiencies upon complexation with Lipofectamine{\texttrademark}2000. The PEGylation site at the four siRNA termini and PEG molecular weight were not critical factors to significantly affect gene silencing activities. Cleavable siRNA-PEG conjugates showed comparable gene silencing activities to naked siRNA, and exhibited sequence-specific degradation of a target mRNA. Interestingly, noncleavable siRNA-PEG conjugates were processed by Dicer, enabling to exert RNAi effect without showing a target sequence-specific manner. However, only cleavable siRNA-PEG conjugates significantly reduced the extent of INF-α release as compared to noncleavable siRNA-PEG conjugates, suggesting that they can be potentially used for therapeutic siRNA applications.",

keywords = "Cleavable linkage, Conjugate site, Gene inhibition, PEGylation, SiRNA",

author = "Sooyeon Jung and Lee, {Soo Hyeon} and Hyejung Mok and Chung, {Hyun Jung} and Park, {Tae Gwan}",

year = "2010",

month = jun,

doi = "10.1016/j.jconrel.2010.03.002",

language = "English",

volume = "144",

pages = "306--313",

journal = "Journal of Controlled Release",

issn = "0168-3659",

publisher = "Elsevier",

number = "3",

}

TY - JOUR

T1 - Gene silencing efficiency of siRNA-PEG conjugates

T2 - Effect of PEGylation site and PEG molecular weight

AU - Jung, Sooyeon

AU - Lee, Soo Hyeon

AU - Mok, Hyejung

AU - Chung, Hyun Jung

AU - Park, Tae Gwan

PY - 2010/6

Y1 - 2010/6

N2 - Small interfering RNA (siRNA) was conjugated with poly(ethylene glycol) (PEG) at four different terminal ends (sense 3', sense 5', antisense 3', and antisense 5') via cleavable disulfide and noncleavable thioether linkages to evaluate their gene silencing efficiencies upon complexation with Lipofectamine™2000. The PEGylation site at the four siRNA termini and PEG molecular weight were not critical factors to significantly affect gene silencing activities. Cleavable siRNA-PEG conjugates showed comparable gene silencing activities to naked siRNA, and exhibited sequence-specific degradation of a target mRNA. Interestingly, noncleavable siRNA-PEG conjugates were processed by Dicer, enabling to exert RNAi effect without showing a target sequence-specific manner. However, only cleavable siRNA-PEG conjugates significantly reduced the extent of INF-α release as compared to noncleavable siRNA-PEG conjugates, suggesting that they can be potentially used for therapeutic siRNA applications.

AB - Small interfering RNA (siRNA) was conjugated with poly(ethylene glycol) (PEG) at four different terminal ends (sense 3', sense 5', antisense 3', and antisense 5') via cleavable disulfide and noncleavable thioether linkages to evaluate their gene silencing efficiencies upon complexation with Lipofectamine™2000. The PEGylation site at the four siRNA termini and PEG molecular weight were not critical factors to significantly affect gene silencing activities. Cleavable siRNA-PEG conjugates showed comparable gene silencing activities to naked siRNA, and exhibited sequence-specific degradation of a target mRNA. Interestingly, noncleavable siRNA-PEG conjugates were processed by Dicer, enabling to exert RNAi effect without showing a target sequence-specific manner. However, only cleavable siRNA-PEG conjugates significantly reduced the extent of INF-α release as compared to noncleavable siRNA-PEG conjugates, suggesting that they can be potentially used for therapeutic siRNA applications.

KW - Cleavable linkage

KW - Conjugate site

KW - Gene inhibition

KW - PEGylation

KW - SiRNA

UR - http://www.scopus.com/inward/record.url?scp=77953287100&partnerID=8YFLogxK

U2 - 10.1016/j.jconrel.2010.03.002

DO - 10.1016/j.jconrel.2010.03.002

M3 - Article

C2 - 20206653

AN - SCOPUS:77953287100

SN - 0168-3659

VL - 144

SP - 306

EP - 313

JO - Journal of Controlled Release

JF - Journal of Controlled Release

IS - 3

ER -

Gene silencing efficiency of siRNA-PEG conjugates: Effect of PEGylation site and PEG molecular weight

Abstract

Funding

Keywords

Access to Document

Other files and links

Fingerprint

Cite this