A more powerful way to develop therapeutics?

July 21, 2016, University of Toronto

A University of Toronto scientist has developed a new method for identifying the raw ingredients necessary to build 'biologics', a powerful class of medications that has revolutionized treatment of diseases like rheumatoid arthritis and some cancers.

Biologics are a type of drug that results from the high-tech manipulation of our own proteins, as opposed to more traditional drugs built from synthetic chemicals. Because of their success so far, scientists are racing to create new biologics - and now, a University of Toronto researcher has developed a way to make that process more powerful.

Philip M. Kim, an associate professor in U of T's Donnelly Centre for Cellular and Biomolecular Research, combined high-tech computer simulation and high-throughput laboratory experiments to create what he hopes will be the most effective way to discover the proteins that are key to new biologics. His research was published online in the journal Science Advances on July 20, 2016.

"A large fraction of new therapeutics these days involve engineered proteins that latch onto a , for instance on a cancer cell," says Kim, also of the departments of Molecular Genetics and Computer Science. "Finding a protein that effectively binds to a target can feel like looking for a needle in a haystack. Our method should open up new opportunities to find those key proteins - and make a major impact on the development of new biologics."

Under the traditional approach to developing a biologic, researchers identify a protein of interest and then test billions of variants, either randomly generated or from a natural source, hoping to find an effective binder. But these methods allow very little control over where and how the performs this crucial function on its target - a major factor in its effectiveness.

Kim and his team took a different approach. They used a computer to simulate the binding process, and then designed proteins that would work on the target. This type of theoretical approach has been in development for several decades, but is still not effective enough. So Kim combined the best of both methods. Instead of randomly creating massive libraries of variants, as with the traditional approach, he used computer modelling to generate a smaller, but intelligently designed repertoire of variants. Designing each variant allows for the tight control of all its properties, in contrast to conventional approaches.

"We showed that this method gives you binders that are somewhat stronger than what you get with the conventional approach," says Kim. "The much smaller library also solves many technical problems, and we can screen for new, previously unscreenable, targets. It's a very exciting time for cancer research, and for biologics."

For Kim, the next step is to produce proteins that are important to certain types of cancer, but have not been screened before due to the difficulty producing them.

Explore further: Researchers map molecular 'social networks' that drive breast cancer cells

More information: M. G. F. Sun et al, Protein engineering by highly parallel screening of computationally designed variants, Science Advances (2016). DOI: 10.1126/sciadv.1600692

Related Stories

Researchers map molecular 'social networks' that drive breast cancer cells

July 14, 2016
A powerful new technology that maps the "social network" of proteins in breast cancer cells is providing detailed understanding of the disease at a molecular level and could eventually lead to new treatments, Australian scientists ...

Permeon reveals discovery of Intraphilins as new approach to intracellular biologic drugs

July 28, 2011
Permeon Biologics, a biopharmaceutical company pioneering a novel class of intracellular protein biologics, today announced the discovery of an entirely new class of naturally occurring human supercharged proteins called ...

Tackling a large challenge for new modes of drug delivery

November 12, 2013
New treatments for prostate cancer, multiple sclerosis and cystic fibrosis could be developed following research being carried out into how medicinal 'biologics' can be delivered to diseased cells.

Biologics for asthma: Attacking the source of the disease, not the symptoms

November 5, 2015
Imagine you suffer from severe asthma, and you've tried every treatment available, but nothing has worked. You still can't breathe. Then a new therapy comes along that attacks the source of the asthma, as opposed to the symptoms, ...

Recommended for you

Long-term estrogen therapy changes microbial activity in the gut, study finds

June 20, 2018
Long-term therapy with estrogen and bazedoxifene alters the microbial composition and activity in the gut, affecting how estrogen is metabolized, a new study in mice found.

Are you sticking to your diet? Scientists may be able to tell from a blood sample

June 19, 2018
An analysis of small molecules called "metabolites" in a blood sample may be used to determine whether a person is following a prescribed diet, scientists at Johns Hopkins Bloomberg School of Public Health have shown.

Everything big data claims to know about you could be wrong

June 19, 2018
When it comes to understanding what makes people tick—and get sick—medical science has long assumed that the bigger the sample of human subjects, the better. But new research led by UC Berkeley suggests this big-data ...

Diagnosing and treating disorders of early sex development

June 19, 2018
Diagnosing, advising on and treating disorders of early sex development represent a huge medical challenge, both for those affected and for treating physicians. In contrast to the earlier view, DSD (Difference of Sex Development) ...

BPA can induce multigenerational effects on ability to communicate

June 18, 2018
Past studies have shown that biparental care of offspring can be affected negatively when females and males are exposed to bisphenol A (BPA); however, previous studies have not characterized how long-term effects of BPA exposure ...

New compound shown to be as effective as FDA-approved drugs against life-threatening infections

June 15, 2018
Purdue University researchers have identified  a new compound that in preliminary testing has shown itself to be as effective as antibiotics approved by the Food and Drug Administration to treat life-threatening infections ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.