In Huntington's disease, which afflicts about one in 10,000 Americans, one gene is defective -- making it difficult for patients to walk, talk or swallow.

So, if there was a way to "silence" that one gene there could potentially be a cure.

That's the promise of RNA interference technology, and it has three Seattle-area companies trying to find a way to make it deliver. 

"There has been no other technology that has been capable of shutting off aberrant genes," said H. Stewart Parker, the chief executive of Seattle-based Targeted Genetics.

The two companies had been working together on the program since 2005.

Like other Seattle-area companies working on RNAi, Targeted Genetics is confronting one of the barriers challenging RNAi's promise: how to efficiently and safely deliver RNAi molecules to cells. 

Targeted Genetics is trying to deliver RNA molecules by linking them to the adeno-associated virus, a naturally occurring virus that the company is also using to develop treatments for inflammatory arthritis and HIV/AIDS.

Targeted Genetics' Parker said that method was advantageous because it essentially created "a little factory" ensuring that the RNAi molecules do not have to be repeatedly redosed and have a longer effect. 

"We think for diseases in the brain (such as Huntington's disease), it's the best alternative," she said. "When you're going to introduce drugs to the brain you don't want to do that very often."

Parker said that Targeted Genetics is conducting long-term studies of the treatment in animals and that it could enter clinical trials in late 2009. 

PhaseRX, a Seattle-based startup that in February landed commitments for up to $19 million in venture capital funding, is developing synthetic polymers to move RNAi molecules across cell membranes.

"These polymers actually mimic some of the viral (proteins) and the way they get into cells," said founder Robert Overell in an interview when PhaseRX announced its funding. He declined to elaborate Monday.

A third company, Nastech Pharmaceutical of Bothell, is developing lipid formulations of RNAi molecules. The company says that properly designed lipid formulations can interact with cell membranes and gain access to a cell's interior. The company is also developing peptides to "drag RNAi molecules across," said President Gordon Brandt. 

"We believe our delivery approach is the best one out there," Brandt said. In addition, the company has developed a new set of RNAi molecules that the company says do not overlap with the intellectual property of the field's two major players -- Sirna Therapeutics and Alnylam Pharmaceuticals.

Nastech has identified four therapeutic targets for its RNAi technology -- two against rheumatoid arthritis and influenza and two, in an earlier stage, targeting cardiovascular disease and cancer. 

No clinical trials have started.

"It's a new scientific area," Brandt staid. "There won't be any shortcuts. This is going to be a long process." 

The company hopes RNAi will boost its faltering stock price and business -- which suffered in the wake of the loss of a partnership last fall with Procter & Gamble to develop a nasal spray to treat osteoporosis.

During a March 3 conference call, Nastech CEO Steven Quay said that the company hoped to partner its RNAi technology with a large pharmaceutical company. 

"One of the remarkable things in this area was that Sirna Therapeutics, which was acquired at an early stage by Merck for $1.1 billion, and Alnylam with a market capital of $1.2 billion, each inked $700 million-plus deals with big pharma partners for their preclinical programs," Quay said, according to a transcript.

It was Merck's acquisition of Sirna in 2006 that eventually led to Monday's announcement that Targeted Genetics would buy Sirna's portion of the Huntington's disease partnership, Parker said.

"For simplicity purposes, from their standpoint, it was beyond the focus of what they wanted to do," she said.