Breaker

The audience that sat through Ron Breaker's life sciences keynote speech at TiECON East 2012 was probably a bit overwhelmed with the complexity of his explanation and slides on DNA and RNA. However, one thing was pretty clear — at the end of the day the deep science is all targeted toward the creation of companies to develop products based on the discoveries.

"What really excites me about basic science • is when we decide this can go commercial," said Breaker, who is a professor at Yale University, head of the school's molecular, cellular and developmental biology department and an investigator with the Howard Hughes Medical Institute.

Breaker is the recipient of fellowships from the Arnold and Mabel Beckman Foundation, the David and Lucile Packard Foundation, and the Hellman Family Trust. In recognition of his research accomplishments at Yale, he received the Arthur Greer Memorial Prize in 1997, the Eli Lilly Award in Microbiology in 2005 and the Molecular Biology Award from the U.S. National Academy of Sciences in 2006.

Breaker has fueled his excitement with the formation of two companies that grew out of his research. He conducts research on the advanced functions of nucleic acids, including the discovery and analysis of novel ribozymes, deoxyribozymes and noncoding RNAs. His laboratory also studies ligand-binding RNAs called riboswitches that control gene expression in many species from all three domains of life.

In 2001, Breaker co-founded Archemix, a Cambridge, Mass.-based biotechnology company developing engineered aptamers as therapeutic agents. In 2005, he co-founded BioRelix, a New Haven, Conn.-based biotechnology company developing antibiotics that target bacterial riboswitches.

During his keynote at TiECON East 2012, he told the audience he also has plan for a third company.

In the lab, Breaker said the road to market usually starts when "the light bulb goes off." However, he pointed out that when it comes to commercialization of science the light bulb moment is critical, but just a small part of the process. "There is an enormous trial of events that have to happen until something goes commercial," he added.

Breaker's light bulb moment, which has led to the formation of two companies with a third on the way, was when his lab made some discoveries about DNA and RNA and, in particular, riboswitches.

"In the early days of our lab we had no intention of finding something that would be of use. We just wanted to probe a little bit of the ancient world," Breaker said. "But then we realized we can create things in the laboratory much like natural evolution creates these things over millions of years.

"We can use DNAs to create things that perhaps nature never intended to do," he added. "We can make DNA do chemistry."

Before the audience envisioned some Frankenstein-like creation, Breaker broke it down into layman's terms to say that they were able to exploit the properties of DNA to react in certain ways to chemicals and compounds, thus making reliable biosensors.

Archemix was created as a company to develop these biosensors for commercial uses ranging from detecting contamination from heavy metals to detecting the amount of caffeine in soda.

This work led Breaker and his colleagues to further examine riboswitches and uncover their effectiveness as possible drug compounds. BioRelix was created to commercialize types of riboswitches as drugs. "They have novel compounds and they are killing bacteria in animals," Breaker said.

The fact that the existence of riboswitches was uncovered to begin with has Breaker exited about the future. "We want to find more things like riboswitches," he said. "We are trying to find novel RNA that do things."

According to Breaker, in their work, he and his fellow researchers have found things that such as "big mystery molecules" that they, admittedly, just have "no clue" as to their function. "We just think there is a lot of interesting biology to find," he said. "There are certainly thing that we have no idea what they do."

Breaker's lab has found 25 riboswitches so far, which they believe are nothing more than grains of sand on a beach of riboswitches. "We think there are millions and millions of riboswitches," he said. And if each one has some possible use and eventual commercial application you can only imagine the market potential, he pointed out.

"We want to find the strongest RNAs that will teach the most about biology in the past, present and future," he added.

The latest discovery deals with the interaction between RNA and fluoride that can potentially make the bacteria-killing compound more effective. Breakers believes this will lead to new ideas for new drugs, particularly topical anti-infectives.

While Breaker anticipates this discovery will lead to another company to commercialize it, he points out they are still at the stage when it pays to be careful. "I want the science to be mature enough that it is not going to let the company down," he said. "If a company fails, I want it to be because of the business not the science."