By Doug Macron
Privately held Ablitech last week announced that it has received a $2 million grant from the US Department of Defense to develop its siRNA delivery technology for the treatment of heterotopic ossification, a condition characterized by painful bone growths following injuries and trauma.
According to Ablitech CEO Ken Malone, the company first approached the DoD's Telemedicine and Advanced Technology Research Center in early 2009 about funding for its delivery technology, dubbed Versadel, as a means to treat cancer, the company's primary area of interest.
The TATRC, however, “requested Ablitech employ Versadel to address the problem of treating bone disorders associated with severe trauma,” he said in a statement.
The Versadel technology involves creating a thin shell by linking a hydrophilic polymer to an oligonucleotide, a characteristic that the company touts as eliminating the possibility of siRNA leakage.
“It's not nano-encapsulation, which tends to be the trend these days,” Malone told Gene Silencing News. He added that Versadel molecules have also been shown to be stable in serum for up to 48 hours.
In 2008, Ablitech received a grant from the National Science Foundation to develop the technology, then called Poly-RNA, for the delivery of siRNAs targeting pancreatic cancer (GSN 7/10/2008). In those experiments, Versadel-delivered siRNAs against the genes KIF and Kras achieved a functional response in cancer cells, according to the company.
In other in vitro studies, Versadel siRNAs were taken up by mouse bladder cancer cells, and knocked down expression of the reported gene LacZ by 57 percent after 96 hours of exposure with no toxicity.
With these findings and the funding from the DoD, Ablitech is now advancing into in vivo testing in heterotopic ossification.
Malone said that there are a handful of targets for the condition that have been identified by other groups, and Ablitech is currently contacting oligo providers about obtaining siRNAs against them. “We're taking those payloads and doing our modification and seeing if we can't get them to deliver properly,” he said.
About a year ago, researchers from Peking University reported that siRNAs against Runt-related protein 2 and Smad4, which are involved in osteoblast differentiation, inhibited heterotopic ossification in rats. In 2006, the same group published data pointing to Runx2 as a target for RNAi intervention in the condition.
He told Gene Silencing News that these two targets are “of high interest.”
“We would hope that at the end of this grant, we would have minimal efficacy data” in rodents, Malone said. “That will position us to raise money to go into more extensive animal studies across a much broader range of diseases.”
Malone said that Ablitech's key in-house focus is on oncology, especially bladder cancer, which would involve local delivery via catheter and therefore sidestep the technological hurdles currently facing systemically delivered siRNA drugs.
“While we think our technology is the answer for systemic [delivery], we're pretty rational about the timeframe of getting there,” he said. “So things that [involve] direct delivery are a high priority for us.”
Heterotopic ossification, he noted, would also be addressed using siRNAs administered to the target site.
“We would take this polymer shell we put on an siRNA and [adjust its] hydrophobicity so it stays local,” he said, adding that while the military applications of such a treatment would primarily be amputations, it would also be useful for treating the bone growths that sometime occur as a result of knee and hip replacement procedures.
The DoD grant is set to run for one year, but includes a possible extension period, so Malone expects the work on heterotopic ossification to run for about a year and a half, at which point Ablitech is expected to have generated sufficient in vivo data to woo an industry partner interested in either partnering on the heterotopic ossification or cancer programs, or using the Versadel technology within its own RNAi programs.
“We've been out and spoken to almost everybody that is involved in RNAi,” he said. “The pretty clear response is, 'Hey, let's see some animal data before we jump in.' Our view is to develop animal data and [then] … to do some licensing deals.”
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