BioWorld Today Contributing Writer

Flush with new grant funding, Sirnaomics Inc., in partnership with its overseas subsidiary, Sirnaomics China Co. Ltd., of Suzhou, China, is moving forward with development of multitarget RNA interference therapies for 11 different preclinical programs including wound healing, influenza and glioblastoma. Gaithersburg, Md.-based Sirnaomics is separating itself from the rest of the RNAi pack by taking a multitarget approach to gene silencing.

"One siRNA to silence one gene doesn't always result in a viable therapeutic," Sirnaomics Vice President of Discovery Research David Evans told BioWorld Today.

Multitarget therapeutics have been appearing in many pharmaceutical and biotech pipelines due to the influence of systems biology and past failures of single-target therapeutics in complex diseases like cancer. Taking that premise into the field of gene silencing, Sirnaomics believes it can produce a more effective RNAi therapy by targeting multiple genes simultaneously.

"We took the approach that multiple siRNAs, targeting either multiple regions along the same gene to improve efficacy or preferably multiple genes in a signaling cascade can actually improve the outcome for a therapeutic," Evans said.

The company's lead program is in scarless wound healing. It started with the observation that wounds to a fetus, such as in prenatal surgery, heal without scarring because certain genes are down-regulated.

The hypothesis, then, was that silencing those genes in an adult would allow the healing of wounds without scars.

Sirnaomics scientists identified two genes, TGFβ1 and Cox-2 that have been associated with the phenomenon in the literature and developed siRNAs against those targets.

For a delivery method, they borrowed the histidine lysine polymer (HK polymer) nanoparticle system from James Mixson, of the University of Maryland. Histidine and lysine are natural carriers of nucleic acids, and the branched polymer developed by Mixson buffers the RNA and assists in its release within the cells.

In the area of antivirals, Sirnaomics has an investigational gene silencing therapy for influenza that may inhibit replication of H5N1 avian flu as well as HIN1 seasonal flu. It is focusing on silencing multiple conserved regions of the viral genome in order to thwart the virus's noted ability to mutate and become resistant. For example, last flu season saw a "tremendous increase in Tamiflu-resistant strains," according to Evans.

Currently available countermeasures for avian and seasonal flu virus include flu vaccine and antivirals such as Tamiflu (oseltamivir) and Relenza (zanamivir). Sirnaomics reported that its gene silencing cocktail rescued 60 percent of avian flu-exposed mice, compared to just 40 percent for Relenza.

Sirnaomics has little serious competition in producing siRNA-based influenza therapies.

A deal between Alnylam Pharmaceuticals and Novartis International AG in 2006 to develop a gene-silencing therapy against influenza, and seeded by a $250,000 grant from the Defense Advance Research Projects Agency, was initially predicted to be in clinical trials by 2007. That program remains preclinical, according to Alnylam's website, and the program was reported stalled in 2007 due to lack of efficacy. (See BioWorld Today, Feb. 22, 2006, and BioWorld Insight, Sept. 3, 2007.)

Marina Biotech, of Bothell, Washington, formerly MDRNA, Inc., reported positive in vivo results with an RNAi-based therapeutic in 2008, but no further news has come out of that program and it no longer appears in the company's official pipeline.

If Sirnaomics is right, multitarget RNAi therapeutics may allow it to crack a nut that so far has resisted efforts by larger companies.

Sirnaomics is involved in numerous collaborations with academic institutions in the U.S. and Asia, including the University of Tennessee, the University of Pittsburgh, Johns Hopkins University, Duke University and Hong Kong University. Sirnaomics also has ties with Silence Therapeutics plc, via the former Intradigm Corp., at which Sirnaomics President and CEO Patrick Lu served as vice president from 2001 to 2006. (See BioWorld Today, Dec. 17, 2009.)

Subsidiary operations in China have allowed Sirnaomics to take advantage of VC networks and local government incentives in the Suzhou Industrial Park Biobay area, outside of Shanghai. The company employs 10 people in Maryland and 15 in Suzhou. It also has operations in Guangzho, capital of China's Guangdong province, which the company hopes to expand.

"There are multiple pharmaceutical companies very much interested in our programs, and we believe they're going to have another push for development in China of our siRNA therapeutics program," said George Ji, vice president of corporate development for Sirnaomics.

The company is operating on just over $500,000 in small business innovation research grants from the National Institute of Allergy and Infection Diseases and the National Cancer Institute.

Going forward, Sirnaomics will seek additional grant and partnership opportunities to fund its discovery and development programs.