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Startup SilaGene Aims to Develop U1 Adaptor Gene-Silencing Tech as Therapeutic Platform

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By Doug Macron

Aiming to explore the therapeutic potential of a novel gene-silencing method he developed, Rutgers University researcher Sam Gunderson has founded a small New Jersey-based startup, SilaGene, to conduct the proof-of-concept animal experiments necessary to show the technology works in vivo.

At this point, however, SilaGene remains a two-man operation in need of financing, and funding from the National Institutes of Health will be vital for the company to generate that data, Gunderson told RNAi News this week.

SilaGene’s core technology is the so-called U1 adaptor, which is essentially a single-stranded oligonucleotide composed of a target-gene binding domain and a U1 domain that attracts and inhibits the cellular splicing apparatus. Together, these block the pre-mRNA maturation step of polyA tail addition, according to Rutgers.

In conceiving SilaGene, Gunderson realized that a new company developing the U1 adaptor technology as a research reagent would face an uphill climb given the competitive and crowded life science tools market, and that a more established partner would be needed.

As such, the commercial rights to the technology for research applications have been licensed to Integrated DNA Technology, which has also been helping Gunderson refine the U1 adaptors (see RNAi News, 9/3/2009). All this leaves SilaGene with a license from Rutgers to the core intellectual property covering the technology — a World Intellectual Property Organization patent application, WO 2008/121963 A2 — and the freedom to pursue its development as a therapeutic modality.

Thus far, SilaGene has been operating on a “little bit of seed money” provided by the New Jersey Commission of Science and Technology through Rutgers, Gunderson said. However, this funding “was just enough to incorporate and to pay some legal [costs] — not enough to really get operating,” he said.

For that, the company will need to win Small Business Innovation Research grants from the NIH. And while it has submitted applications for the grants, they have thus far fallen short of meeting the agency’s requirements.

“We’ve made submissions and gotten good scores back, but not good enough yet for funding,” Gunderson said. At the moment, “I’m in negotiations with NIH funding officers … and we’ll go back with more grants and revised grants.” He added that he hopes to begin securing grant funding before the end of the year.

In the meantime, SilaGene is conducting as much of the proof-of-concept work as possible with its limited resources and small staff, which includes Gunderson, who is the company’s CEO, and former Rutgers investigator Rafal Goraczniak, who is the firm’s CSO.

“We have [also] … initiated collaborations with several of the faculty at Rutgers to go the in vivo route,” Gunderson said. “But without any significant funding, things will be slower than we’d like.”

Should SilaGene secure the needed level of NIH support, Gunderson said he hopes to begin exploring in earnest the potential of the U1 adaptors to shut down expression of target genes in key organs and tissues he views as the “lowest-hanging fruit.”

U1 adaptors, he said, resemble antisense oligos because they are single-stranded and relatively short, “and there are a number of different organs and tissue types that take up single-stranded oligos like the liver and lung tissue.”

And because SilaGene has not yet begun looking at delivery technologies for the oligos, “we’re choosing targets that would not, at least in principle … need special delivery,” he said.

First up would be to examine the ability to deliver the U1 adaptors to the liver. “That can be done at several levels,” Gunderson said. “It can be the simple silencing of reporter genes in mice, as well as affecting cholesterol.”

He noted that the company also expects to conduct animal studies showing that the oligos can impact tumor growth. “So we have several programs, but the most important thing is the proof of concept,” he noted. “If we can show that, it will significantly increase interest in the technology.”

And it isn’t just the interest of the NIH Gunderson is hoping to pique.

“Right now, we’re reaching out to biotechnology companies, as well as big pharma, looking for who wants to go forward with us to develop the technology,” he said. “I have presented to several … companies, and … they are all interested and think it’s a very cool technology, especially because it can be combined with RNAi to get deeper silencing or … used as a stand-alone method.”

Potentially helping Gunderson’s case was the March publication of in vitro data in Nature Biotechnology showing that the U1 adaptors could be used to inhibit reporter and endogenous transcripts with IC50s in the nanomolar range. Gunderson, Goraczniak, and IDT CSO Mark Behlke authored the paper.

“Of course, all that was in the publication was cell culture” data, he noted, adding that the bigger pharmaceutical and biotech firms want to see in vivo data before committing to a formal collaboration.