It’s not easy to give a mouse hepatitis. Scientists must modify the creature’s liver and coax a virus to infect it.
It’s even harder to rid a mouse of hepatitis – a crucial step before curing people.
Scientists at Sirna Therapeutics in Boulder, however, have done both.
In July, Sirna published a paper that rocked the biotechnology world. Company researchers conquered a major problem in using RNA interference, one of the most promising new drug-discovery techniques: how to deliver RNA drugs to the right place in nontoxic doses.
“This is going to change medicine,” said John Rossi, a researcher with the Beckman Research Institute, a biomedical research center in Duarte, Calif. “What they did was innovative.”
RNA, a genetic material similar to DNA, helps regulate a cell’s activities.
Since July 22, the last trading day before Sirna’s announcement, the stock price has climbed about 66 percent to $4.36 Thursday. The shares, which traded at $8.28 in June 2002, had dropped to $1.67 at the beginning of July.
“This is important. For RNAi (interference) to be successful as a technology, it’s all about delivery,” said biotechnology analyst Michael King with Rodman and Renshaw Inc. in New York City.
Sirna researchers crafted snippets of RNA that can switch genes on and off, or thwart nasty viruses by slicing up their genes, company officials said.
They’ve also figured out how to “decorate” their RNA drugs with fat-like molecules, to keep them stable and nontoxic in the body – a breakthrough.
The work was published in Nature Biotechnology July 24.
The technique has worked now in petri dishes, mice and monkeys, which have been cured of hepatitis with no side effects, Sirna officials said.
“To be able to do selective gene silencing, that’s the Holy Grail of medicine,” said Howard Robin, Sirna’s chief executive.
Such claims for new techniques have been made before, said Barron Lerner, a medical historian and internist at Columbia University in New York.
Gene therapy, for example, has not delivered on its clinical promise, Lerner said, while bone marrow transplants for leukemia have been successful.
“History is full of examples in both directions,” Lerner said.
Still, in 2002, Science magazine called a string of RNA interference discoveries the No. 1 breakthrough of the year.
Since then, biotechnology companies have sprung up or changed tack to capitalize on the technique. Sirna, once the struggling company Ribozyme, is among the leaders, Rossi said.
Nevertheless, Sirna has posted five years of net losses and seen revenues dwindle to $1.5 million a year from $15 million, according to company filings.
During RNA interference, “silencing” RNA attacks messenger RNA, slicing up the messages and preventing certain proteins from forming. It can also target the genetic material in a virus.
Researchers can design bits of RNA to attack only one target – a viral gene or a messenger RNA carrying bad directions from a mutated gene.
“We’re tapping into a natural mechanism that’s inside the cell,” said David Morrissey, a biologist with Sirna.
Sirna’s big advance this summer was packaging the RNA drugs so they were delivered to the right organ – the liver, in the case of hepatitis – in nontoxic, low doses, Morrissey said.
Human clinical trials with a hepatitis B drug begin in a few months, Morrissey said.
Sirna is already midway through trials of an RNA-based treatment for macular degeneration, a form of blindness.
Staff writer Katy Human can be reached at 303-820-1910 or khuman@denverpost.com.
