Article
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Preserved in Portico This version is not peer-reviewed
Triggering RNA Interference by Photoreduction under Red Light Irradiation
Version 1
: Received: 3 May 2023 / Approved: 4 May 2023 / Online: 4 May 2023 (10:22:20 CEST)
A peer-reviewed article of this Preprint also exists.
Rühle, J.; Klemt, I.; Mokhir, A. Triggering RNA Interference by Photoreduction under Red Light Irradiation. Molecules 2023, 28, 4204. Rühle, J.; Klemt, I.; Mokhir, A. Triggering RNA Interference by Photoreduction under Red Light Irradiation. Molecules 2023, 28, 4204.
Abstract
RNA interference (RNAi) using small interfering RNAs (siRNAs) is a powerful tool to target any protein of interest and is becoming more implementable for in vivo applications due to recent developments in RNA delivery systems. To exploit RNAi for cancer treatment, it is expedient to increase its selectivity by e.g. a prodrug approach to activate the siRNAs upon external triggering, e.g. by using light. Red light is especially well suitable for in vivo applications due to its low toxicity and higher tissue penetration. Known molecular (not nanoparticle based) red light activatable siRNA prodrugs rely on singlet oxygen (1O2) mediated chemistry. 1O2 is highly cytotoxic. Additionally one of the side products in the activation of the known siRNA prodrugs is anthraquinone, which is also toxic. We here report on an improved red light activatable siRNA prodrug, which do not require 1O2 for their activation. The 5’ terminus of its antisense strand is protected with an electron-rich azobenzene promoiety. It gets reduced and cleaved upon red light exposure in the presence of Sn(IV)(pyropheophorbide a)dichloride acting as a catalyst and ascorbate required as a bulk reducing agent producing active siRNAs.
Keywords
siRNA prodrug; selective cancer targeting; red light activation; photoreduction; RNAi; azobenzene
Subject
Chemistry and Materials Science, Medicinal Chemistry
Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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