By Mary Welch
With eight of the top 20 pharmaceutical companies using its antisense program, Sequitur Inc. is well poised to contribute to drug development thanks to its sequence-based compounds for functional genomics research, diagnostic and therapeutic applications.
"I was working on an antisense oligonucleotide program at Ontogeny [Inc., of Cambridge, Mass.] and it was going well," said Tod Woolf, the company's vice president of technology development. "But Ontogeny wasn't interested in pursuing it. So several outside associates and I started the company in order to focus on antisense oligonucleotides - genome therapeutics."
An antisense compound can be devised to block the production of any of the 100,000 human and viral proteins. Using Sequitur's antisense technology, a company can determine gene function and validate small-molecule targets by specifically inhibiting gene expression. Inex Pharmaceuticals Corp., of Vancouver, British Columbia, signed on as its first corporate partner and remains one today. Other collaborators include Pharmacia and Upjohn, of Bridgewater, N.J.; Chiron Corp., of Emeryville, Calif.; Genome Therapeutics Corp., of Waltham, Mass.; and Mitotix. Inc., of Cambridge.
For these customers, Sequitur will experimentally determine optimal antisense sites within target genes. For a yearly fee, a client also can obtain non-exclusive research use of Sequitur's current and newly developed functional genomics technology.
"Antisense technology is a very interesting field," Woolf said. "There is always the possibility of malfunctioning oligonucleotides. They may not work or they may not go into the cells. Or they may kill the cells. You also must be careful to see if there is an effect, whether it is due to inhibiting the target gene or whether the effective cell's development was due to some other effect rather than the antisense."
The Natick, Mass.-based company uses its antisense technology to determine gene function and validate small-molecule targets by specifically inhibiting gene expression. Antisense technology is preferred over other methods because it is systematic and only requires the sequence of the targeted RNA. It also has a faster throughput and lower cost than homologous recombination, the company said.
Using its technology, Sequitur can obtain 66 percent to 95 percent inhibition at the RNA level, Woolf said. "We offer our clients several benefits, such as only selecting four to six antisense sequences rather than dozens of sequences. Other advantages are optimized delivery systems as well as collaborative research where we do the biological screening. We also offer antisense chemistries that are highly specific and effective."
An extension of the antisense technology is GeneLink Pathway Elucidation, which combines expression profiling with Sequitur's specific antisense system, in order to define genetic or biochemical pathways.
An additional project involves using stabilized messenger RNA as an alternative to gene therapy for transient expression of proteins. Called Protein Expression Technology , its aim is to use proprietary forms of nuclease stabilized synthetic RNA to express therapeutically relevant proteins in patients.
Now with 15 full-time staffers, Sequitur is funded internally and through collaborative agreements. A future goal is to develop a catalogue of antisense oligonucleotides rather than custom-producing them for clients.