The synthesis and in vitro evaluation of chemically modified siRNAs that contain internal azobenzene derivative spacers for selective and tunable photocontrol of activity

Short interfering RNAs (siRNAs) are biopolymers that are used as post-transcriptional gene regulators and as a natural endogenous defense against attack from viruses. These molecules hold a great deal of interest as pharmaceuticals for the knockdown of unregulated genes, such as in cancers. Through chemical modification of the RNA structure, inherent limitations can be overcome to make better pharmaceuticals. This study investigated the incorporation of azobenzene derivative spacers into the RNA backbone replacing 2 base pairs. A small library of siRNAs were synthesized and then characterized bio-physically through several means. After bio-physical characterization, these siRNAs were tested in vitro against firefly luciferase in order to determine gene silencing efficacy. The ability of these azobenzene siRNAs to be controlled with light was then investigated. Our results indicate that these modifications are well tolerated within the RNAi pathway and have a robust ability to be activated and inactivated with UV (ultraviolet) and visible light to control gene silencing.

Name thesis:degree_name

Master of Science (MSc)

Discipline thesis:degree_discipline

Applied Bioscience

Grantor

University of Ontario Institute of Technology

Year dc:date.issued

2017

Author dc:creator

• Hammill, Matthew

Advisor dc:contributor.advisor

• Desaulniers, Jean-Paul

• siRNA
• Azobenzene
• Photochemical
• Reversible

Language dc:language.iso

en

Handle dc:identifier.uri

https://hdl.handle.net/10155/836

OAI identifier oai:identifier

oai:ontariotechu.scholaris.ca:10155/836