Date/Time
Date(s) - 16/01/2025
1:30 pm - 2:20 pm

Title: Photoswitchable siRNAs: A Gene-Silencing Symphony Light Show

Date: Thursday January 16, 2025

Time: 1:30-2:20pm

Room: ABB 165

Host: Dr. Katherine Bujold

Abstract:
Short-interfering RNAs (siRNAs) are gene-silencing oligonucleotides that have an important role in biotechnology applications and oligonucleotide-based therapeutics. For example, siRNAs are important to elucidate gene function and to characterize complex biological pathways. One of the challenges in using siRNAs involves controlling its use once administered inside of the cell.  One way to control an siRNA material is to use a photoswichable molecule called azobenzene. Azobenzene is characterized by two ?_max areas, a ? to ?* transition in the UV area that has a large extinction coefficient, and a weak n to ?* transition in the visible area. For azobenzene, UV light promotes a trans to cis isomerization via ? to ?* excitation, whereas visible light promotes a cis to trans isomerization via n to ?* excitation. We have developed an siRNA material that contains an azobenzene embedded within its structure and this can be reversibly activated and inactiavted within cells with visible and UV light, respectively. We have also developed ortho-functionalized tetra-chlorinated and tetra-fluorinated azobenzene derivatives that are capable of isomerizing between cis and trans with different colored lights. Our tetra-fluorinated azobenzene-containing siRNA system is highly robust, and gene silencing can be controlled in vivo in Japanese Medaka (Oryzias latipes).

Keywords: azobenzene, RNA, gene-silencing, red-shift, fluorescence

Biography:
Jean-Paul Desaulniers, PhD is a Professor of Chemistry at Ontario Tech University, and is the current Ontario Tech Research Excellence Chair in Chemical Biology where he leads cutting-edge research in the field of chemical biology. His expertise centers on nucleic acid chemistry, with a focus on designing and synthesizing novel nucleic acid derivatives for therapeutic applications like RNAi.

A native of London, Ontario, Dr. Desaulniers completed his undergraduate degree in Chemistry and Biochemistry at Western University in 2000. He then pursued his PhD at Wayne State University under the mentorship of Dr. Christine Chow, where his research focused on the organic synthesis of pseudouridine and its role within RNA. Following his doctoral studies, Dr. Desaulniers held a prestigious American Cancer Society postdoctoral fellowship at the University of Michigan, working in Dr. Anna Mapp’s lab. There, he designed small-molecule inhibitors to target protein-protein interactions.

Since joining Ontario Tech in 2008, Dr. Desaulniers has built a robust research program. His work explores the synthesis of nucleic acid derivatives, such as photoswitchable siRNAs, which can be used to control gene silencing in biological systems. His group has achieved notable success in creating tetrafluorinated azobenzene-functionalized siRNAs, which can be optically activated using light to regulate gene expression in model organisms like Japanese Medaka fish embryos with collaborator Dr. Simmons from Ontario Tech. His lab was awarded a patent in 2020 for this work, and commercialization funds from NSERC I2I and Lab2Market to further develop this technology.