Arthur Sands calls it the “Mayo Clinic for genes.” And if he gets his way, Lexicon Genetics will emerge as the world’s leading gene knockout company.
With the help of its $220 million IPO last year and an assembled team of more than 350 employees, Lexicon Genetics is preparing to ramp up its knockout efforts and has set a goal of understanding the function of 5,000 genes over five years to aid in target discovery. A crucial component is the genomic Mayo Clinic — Lexicon’s new Genome Pharmaceutical Discovery Center, based in The Woodlands, Texas. The 300,000-square-foot facility will be completed by the end of this year, by which point the ramp-up will be in full swing.
One-third of the center will be “dedicated to an animal facility for the creation and analysis of gene knockouts,” says Sands, president and CEO of Lexicon. That makes it the largest knockout program he’s heard of in the world.
The 5,000 genes to be studied weren’t arbitrarily chosen. Lexicon scientists mined the human genome and mouse databases as well as their proprietary OmniBank database to determine the most promising targets from the human genome. “We’ve prioritized G protein-coupled receptors, all kinases, ion channels, secreted proteins, proteases, and other disease-related enzymes,” Sands says.
Scientists will study the genes using Lexicon’s knockout technologies. Roughly half of the genes selected will be tested with gene-targeting technology, which requires a specific vector for each gene. “This allows us to make very subtle mutations … and complete or conditional knockouts,” Sands explains. The other half will use the high-throughput gene trapping approach, which involves inserting a retroviral vector to trap thousands of genes at a time. The studies will take advantage of Lexicon’s OmniBank, which holds 130,000 mouse embryonic stem cell clones.
Expansion within the company stops just short of adding other creatures to these studies. Still, Sands is delighted that other groups are using knockout technologies on more than just mice. “I see the knockouts in lower organisms actually fueling more gene knockouts in mice. The minute you see an interesting result in … a zebrafish or fruit fly you would want to see the results in a mouse for mammalian [response].”
— Meredith Salisbury