Triggering RNA Interference by Photoreduction under Red Light Irradiation

Rühle J, Klemt I, Mokhir A (2023)

Publication Type: Journal article

Publication year: 2023

Journal

Molecules MDPI

Book Volume: 28

Article Number: 4204

Journal Issue: 10

DOI: 10.3390/molecules28104204

Abstract

RNA interference (RNAi) using small interfering RNAs (siRNAs) is a powerful tool to target any protein of interest and is becoming more suitable for in vivo applications due to recent developments in RNA delivery systems. To exploit RNAi for cancer treatment, it is desirable to increase its selectivity, e.g., by a prodrug approach to activate the siRNAs upon external triggering, e.g., by using light. Red light is especially well suited 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 herein report on an improved redlight-activatable siRNA prodrug, which does not require ¹O2 for its activation. In fact, the 5′ terminus of the antisense strand is protected with an electron-rich azobenzene promoiety. It is reduced and cleaved upon red light exposure in the presence of Sn(IV)(pyropheophorbide a)dichloride acting as a catalyst and ascorbate as a bulk reducing agent. We confirmed the prodrug activation upon red light irradiation both in cell-free settings and in human ovarian cancer A2780 cells.

Authors with CRIS profile

Jennifer Rühle Lehrstuhl für Organische Chemie II Insa Klemt Lehrstuhl für Organische Chemie II Andriy Mokhir Professur für Organische Chemie

How to cite

APA:

Rühle, J., Klemt, I., & Mokhir, A. (2023). Triggering RNA Interference by Photoreduction under Red Light Irradiation. Molecules, 28(10). https://doi.org/10.3390/molecules28104204

MLA:

Rühle, Jennifer, Insa Klemt, and Andriy Mokhir. "Triggering RNA Interference by Photoreduction under Red Light Irradiation." Molecules 28.10 (2023).

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