Multimeric small interfering ribonucleic acid for highly efficient sequence-specific gene silencing.

Nature Materials
Hyejung MokTae Gwan Park

Abstract

Small interfering RNA (siRNA) with 19-21 base pairs has been recently recognized as a new therapeutic agent for effectively silencing a specific gene on a post-transcription level. For siRNA therapeutics, safe and efficient delivery issues are significant hurdles to clinical applications. Here we present a new class of biologically active siRNA structure based on chemically self-crosslinked and multimerized siRNA through cleavable disulphide linkages. The multimerized siRNA can produce more stable and compact polyelectrolyte complexes with less cytotoxic cationic carriers than naked siRNA because of substantially increased charge densities and the presence of flexible chemical linkers in the backbone. The cleavable and multimerized siRNA shows greatly enhanced gene-silencing efficiencies in vitro and in vivo through a target-messenger-RNA-specific RNA interference processing without significantly eliciting immune induction. This study demonstrates that the multimerized siRNA structure complexed with selected cationic condensing agents can serve as potential gene-silencing therapeutics for treating various diseases.

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Citations

Mar 2, 2011·Molecules and Cells·Ki Hyun BaeTae Gwan Park
Apr 9, 2013·Molecules and Cells·Tae Yeon LeeDong-Ki Lee
Mar 23, 2011·Pharmaceutical Research·Ji Hoon JeongSun Hwa Kim
Jun 5, 2012·Nature Nanotechnology·Hyukjin LeeDaniel G Anderson
Jul 14, 2011·Nucleic Acid Therapeutics·Chan Il ChangDong-ki Lee
Jan 10, 2012·Nucleic Acid Therapeutics·Chan Il ChangDong-Ki Lee
Dec 1, 2010·Therapeutic Delivery·Olivia M MerkelThomas Kissel
Feb 11, 2014·Nucleic Acid Therapeutics·Burcu BestasSamir El Andaloussi
Mar 19, 2013·Trends in Molecular Medicine·Jianfeng GuoCaitriona M O'Driscoll
Sep 19, 2012·Biotechnology Advances·So Jin LeeKwangmeyung Kim
May 18, 2013·Advanced Drug Delivery Reviews·Koen RaemdonckStefaan C De Smedt
Nov 14, 2013·Antioxidants & Redox Signaling·Philipp M Klein, Ernst Wagner
Mar 1, 2012·Nature Materials·Jong Bum LeePaula T Hammond
Dec 22, 2011·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Jianfeng GuoCaitriona O'Driscoll
Feb 9, 2012·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Dongkyu KimSun Hwa Kim
Nov 30, 2011·Journal of Controlled Release : Official Journal of the Controlled Release Society·Claudia Scholz, Ernst Wagner
Feb 8, 2011·Journal of Controlled Release : Official Journal of the Controlled Release Society·Ru ChengZhiyuan Zhong
Dec 28, 2010·Journal of Controlled Release : Official Journal of the Controlled Release Society·Soo Hyeon LeeTae Gwan Park
Dec 25, 2010·Biomaterials·Soo Hyeon LeeTae Gwan Park
Sep 22, 2010·Journal of Controlled Release : Official Journal of the Controlled Release Society·In-Hyun LeeSangyong Jon
Jan 25, 2012·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Keita UnMitsuru Hashida
Oct 4, 2015·Journal of Controlled Release : Official Journal of the Controlled Release Society·Corey J BishopJordan J Green
Jul 4, 2013·Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology·Kristen L KozielskiJordan J Green
Jan 10, 2012·The Journal of Gene Medicine·Chan Il ChangDong-Ki Lee
Feb 7, 2013·Biochemical and Biophysical Research Communications·Amir Abbas MokhtariehMyung Kyu Lee
Aug 24, 2013·Journal of Controlled Release : Official Journal of the Controlled Release Society·Bin QinKun Cheng
May 28, 2014·Journal of Controlled Release : Official Journal of the Controlled Release Society·Min Kyung JooKwangmeyung Kim

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