Lab-created "frankenproteins" developed by a team of scientists at the University of Toronto Mississauga offer hope for safer and more effective cancer treatments in the future.
The protein-based drugs being developed by Jumi Shin and her students are described as "frankenproteins" because of the way they are created: by cutting and pasting parts of different proteins.
Early versions have been shown to slow tumour growth in some aggressive cancers.
"Our protein drugs are potentially part of the next-generation arsenal against cancers," says Shin, an associate professor in the department of chemical and physical sciences at U of T Mississauga.
Her team employs a strategy known as rational design, where chemists design new proteins based on detailed knowledge of related proteins' structures and functions. This allows researchers to engineer proteins that can be useful in drug development and synthetic biology.
In one recent research paper , Shin and PhD students Raneem Akel and Rama Edaibis used rational design to create a customized protein that can target a specific genetic sequence to regulate gene circuits in cells.
Another paper , co-authored by PhD student Maryam Ali, demonstrates how one of the team's "designer frankenproteins" can inhibit a protein complex called Myc/Max from binding to its DNA target site.
"This is good because Myc, in particular, goes rogue in many cancers," explains Shin. "And currently there is no small-molecule drug that can tackle the Myc/Max network."
The Shin research group's work recently received new funding from the Ontario Institute for Cancer Research through its Cancer Therapeutic Innovation Pipeline. The program provides up to $1 million over two years to develop new anti-cancer treatments. "If successful, these next-generation protein therapies could offer safer and more effective treatments for hard-to-treat breast and ovarian cancers, particularly for patients who have limited options or resistance-prone disease," the OICR said .
The support comes at a critical time for Shin and her team. "This generous funding allows us to enlarge our collaboration and move our proteins forward," Shin says.
Development of these new proteins can be streamlined by using directed evolution, a lab-based method that mimics and speeds up the process of natural selection to move towards a goal.
Shin's team is using highly infectious particles known as phages, which carry DNA with the protein they are trying to mutate and improve. A recent research paper from Shin's group delves into the development of this technique.
"People can make libraries, even large libraries, of mutations. However, with our system, not only can you make large libraries of the particular protein you are trying to mutate and improve for future generations, but the system will also 'choose' the winners," Shin explains.
"We don't have to manually look at every single protein variant and make decisions, as this would be extraordinarily time- and cost-consuming. The biological system does the analysis for us. Then we take a winner and then continue to refine."
Ali says she has high hopes for some of the work coming out of the lab.
"We are expecting our proteins to be used as cancer drugs, as the pathway they inhibit is over-expressed in over 70 per cent of cancers."
