Benitec said this week that it has successfully used its DNA-directed RNA interference technology — which uses a DNA construct to trigger the production of desired double-stranded RNAs for RNAi — to knock down multiple genes at once, a step towards the company’s goal of dealing with drug resistance as it eyes the development of treatments for HIV. Data from these experiments are expected to be published by the first quarter of the next year, according to company officials, although nothing has been submitted to any peer-reviewed journal yet.
According to Ken Reed, Benitec’s director of research and technology, the experiments were conducted in undisclosed in vitro cell systems against undisclosed model genes, and were designed to validate what the company has termed a “multiple warhead” gene-silencing approach. Knockdown effect was seen, he said, for “days to a couple of weeks.”
HIV is Benitec’s priority disease area, CEO John McKinley told RNAi News. The company expects that by targeting multiple genes, RNAi can overcome the difficulties of viral mutations that have made the disease so difficult to treat thus far. An article in this months issue of the Journal of Virology (see story below) highlights this problem, as well as the need to target multiple areas of the virus when using RNAi.
“HIV is a no-brainer for RNAi; it really offers a tremendous amount of promise. It’s a nightmare of a disease, and it’s one that we believe is uniquely tractable to mul- tiple warhead RNAi,” Reed said. He added that Benitec is working towards initiating clinical trials of a ddRNAi treatment for HIV “within the next two years.”
Key to Benitec’s ability to ramp up clinical trials, Benitec CEO John McKinley said, will be the company’s successful establishment of a US subsidiary, which will set the groundwork for the eventual transplantation of the company’s headquarters from Australia to America and the floating of its shares on the NASDAQ.
“I don’t think that, by virtue of its positioning, [Australia] could be a center for Benitec’s development,” he said. “With ddRNAi, we need to be in the main market … and that’s [the US].”
“We’re just about to start the incorporation process,” he said, “but we’ve [still] got to look at … facilities, staff, and then building the entity. I would say that by the first quarter of 2004, we will have an established position in the United States.”
McKinley noted that since a company needs to be incorporated in the US for at least three years before it can conduct an initial public offering, getting Benitec’s stock on a US exchange would likely be effected through a merger with another publicly held firm, either one involved in RNAi or with a shell company.
It is still unclear, however, as to where the subsidiary will be located. While McKinley told RNAi News in August that Benitec was looking at California, possibly San Francisco or San Diego, he said this week that the company is now considering a variety of areas, including ones near Washington DC, Philadelphia, Los Angeles, and San Francisco.
“It’s a little bit open, but we will be established within the first quarter of 2004,” McKinley said. He added that where the subsidiary ends up “may be dependent on where we have a major collaboration. Ob- viously, there’s no point in being at one end of the country if we’re going to be spending a lot of time working [with a partner] on the other.”
Benitec is on the lookout for potential collaborators in both the academic and industry arenas, Reed said, adding to the research partnerships that the company has already established. Last December, the company struck a deal with the Garvan Institute to investigate the role of certain genes in Type II diabetes. About two months later, it formed an alliance with Tranzyme, gaining access to the Research Triangle Park, N.C.-based com- pany’s gene-delivery technologies.
Reed said that a number of discussions are ongoing with potential new collaborators and characterized some of them as “well underway.” McKinley added that he and Reed would be “disappointed if we were not in a position to be partnering within the first or so quarter of 2004.”