Cyclodextrin-containing polymer delivery system for light-directed siRNA gene silencing

Oligonucleotides
S BøeE Hovig

Abstract

In this study, we have investigated the possibility of combining a cyclodextrin-containing polymer (CDP) with siRNA molecules to modulate gene expression in a light-directed manner through photochemical internalization (PCI) technology. We utilized S100A4 as a model gene to evaluate the efficacy of gene silencing. After optimization of carrier/cargo ratio and illumination dose, real-time reverse transcriptase-polymerase chain reaction data showed between 80% and 90% silencing in the siRNA samples treated with PCI compared with untreated control. In contrast, only a 0%-10% silencing effect was detected in the siRNA samples without PCI treatment, demonstrating the potency of light-specific delivery of siRNA molecules. Light-directed siRNA delivery was shown in 2 different cell lines with corresponding potency. Further, time-lapse results demonstrated maximum gene silencing only at 5 hours after endosomal release, implying, for example, rapid carrier decondensation when using the CDP. This work represents a first success in using a CDP delivery agent, without endosomolytic properties for siRNA gene silencing in a light-directed manner, opening the opportunity to use CDPs for light-directed siRNA gene silencing in vivo.

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Citations

Mar 1, 2012·Accounts of Chemical Research·Yuka Matsushita-Ishiodori, Takashi Ohtsuki
Jul 14, 2011·Chemical Communications : Chem Comm·Antonino MazzagliaMaria Teresa Sciortino
Jul 21, 2011·Photochemical & Photobiological Sciences : Official Journal of the European Photochemistry Association and the European Society for Photobiology·Kristian BergAnders Høgset
Jul 14, 2011·Nucleic Acid Therapeutics·Kaushik SinghaWon Jong Kim
Oct 19, 2011·Nucleic Acid Therapeutics·Sigurd L BøeEivind Hovig
Oct 8, 2013·The Nurse Practitioner·Sarah E Smith, Sara J Reeder
Sep 13, 2013·Therapeutic Delivery·Sigurd Leinæs Bøe, Eivind Hovig
May 18, 2013·Advanced Drug Delivery Reviews·Koen RaemdonckStefaan C De Smedt
Sep 13, 2012·Journal of Drug Delivery·Betzaida CastilloGabriel Barletta
Aug 27, 2011·Expert Opinion on Drug Delivery·Kiran ChaturvediTejraj M Aminabhavi
Feb 15, 2013·Nucleic Acid Therapeutics·Jens Andreas Lindin JørgensenSigurd Leinæs Bøe
Mar 28, 2013·Nucleic Acid Therapeutics·Sigurd Leinæs BøeEivind Hovig
Apr 7, 2012·Nucleic Acid Therapeutics·Jens Andreas Lindin JørgensenSigurd Leinæs Bøe
Feb 23, 2020·Journal of Clinical Medicine·Waseem JerjesKristian Berg
Nov 22, 2011·Nanotechnology·Cristiana S O PauloLino S Ferreira
May 4, 2021·Chemical Reviews·Ramya KumarTheresa M Reineke

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Methods Mentioned

BETA
electrophoresis
transfection
PCR

Software Mentioned

Gene Expression Macro
BLAST
Primer Express

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