A chemist at Texas A&M University is developing a new type of therapy for cancer using the unusual binding properties of the mirror images of biological molecules.
Jonathan Sczepanski, who was a postdoctoral fellow at the Scripps Research Institute in La Jolla, California, was recruited in 2015 to the Department of Chemistry at Texas A&M University with the help of a First-Time Tenure-Track Award from CPRIT.
The novelty of Sczepanski’s mirror-image molecules is that they not only bind their targets very specifically but they are also resistant to the normal biological mechanisms that would degrade them inside cells.
His therapeutic targets are microRNAs, which are short segments of RNA that help turn genes on and off inside cells. Many microRNAs are specific to cancer, which makes them a highly sought target for new therapeutics.
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A chemist at Texas A&M University is developing a new type of therapy for cancer using the unusual binding properties of the mirror images of biological molecules.
Jonathan Sczepanski, who was a postdoctoral fellow at the Scripps Research Institute in La Jolla, California, was recruited in 2015 to the Department of Chemistry at Texas A&M University with the help of a First-Time Tenure-Track Award from CPRIT.
The novelty of Sczepanski’s mirror-image molecules is that they not only bind their targets very specifically but they are also resistant to the normal biological mechanisms that would degrade them inside cells.
His therapeutic targets are microRNAs, which are short segments of RNA that help turn genes on and off inside cells. Many microRNAs are specific to cancer, which makes them a highly sought target for new therapeutics.
The mirror-image molecules developed by Sczepanski seek out these microRNA targets, and once they find them, bind tightly and don’t let go. Also, because the mirror-image molecule isn’t found in nature, it isn’t recognized by the cell and destroyed; it slips under the radar and remains intact.
“We don’t really know how it works,” he says, “but the binding seems to be very specific, more so than ordinary binding that’s based on the genetic sequence.”
Once the mirror-image molecule is bound, it shuts down the target microRNA, stopping the genetic pathway that’s essential for the cancer cell’s replication or survival.
Sczepanski’s first target is a microRNA that is over-expressed in prostate cancer. Having shown that his mirror-image molecules work well in a test tube, he’s now focused on demonstrating that they also function in cancer cell lines cultured in the laboratory. The next step would be to test it in an animal model of prostate cancer, to see if it can silence the microRNA in a living organism.
He’s also interested in developing mirror-image molecules to use as diagnostic sensors for cancer and other diseases.
Sczepanski is also studying the process of DNA repair, which is intimately linked to cancer development and progression. He and his team are synthesizing “designer” chromatin that will work in a test tube, which will enable them to study this process in unprecedented detail. He wants to be able to ask and answer questions about chromatin’s role in DNA repair as well as about the epigenetic changes that help facilitate this process.
The CPRIT startup funding was very attractive, he says. “It opened the door for us to purchase crucial instrumentation early on and enabled us to hit the ground running.”
Sczepanski was an undergraduate at the University of Minnesota and received his Ph.D. in Chemistry from Johns Hopkins University. He became a postdoctoral researcher in biochemistry at the Scripps Research Institute in 2010.
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