By Mary Welch

Claiming its technology represents a "vastly different form of gene therapy," Selective Genetics Inc. opened its doors to develop site-specific therapeutics and DNA devices that promote tissue repair and regeneration.

Formed by the merger of Matrigen Inc., of Ann Arbor, Mich., and Prizm Pharmaceuticals Inc., of San Diego, the eight-month-old firm expects to have three products in the clinic by 1999. The company, based in San Diego, combined the core technologies of Matrigen's Gene Activated Matrix (GAM) technology and Prizm's fibroblast growth factor gene targeting technology, called Directin. This combination gives the 45-person firm the ability to deliver genes with high-target cell selectivity for tissue repair, thanks to its molecular, physical and mechanical targeting technologies.

"We are, to my knowledge, the first gene therapy company that specializes in tissue repair and regeneration," said Robert Abbott, former president and CEO of Matrigen, now CEO of Selective Genetics.

Abbott was the former president of Viagene Inc., the largest gene therapy company in the country when it was bought out in 1995 by Chiron Corp., of Emeryville, Calif. "I was out of the gene therapy business and then I heard about this platform technology, GAM. This struck me as a paradigm shift in how people looked at and applied gene therapy."

Until Selective Genetics, virtually all gene therapies were administered in a liquid form, such as naked DNAs, viral vectors or liposomes. As a result, they were not practical to use in acute injury situations.

"Acute injury situations constitute the largest area of medical need," said Abbott. "It includes everything from dermal ulcers to fractures, spinal cord injuries, heart attacks, and even stroke. It's a growing and vastly overwhelming area of medical need. But gene therapy couldn't be used because you couldn't put a dripping liquid into such an area."

What Matrigen did was take a gene and immobilize it in a matrix that could then be applied to an injury site. The genes in the matrix are held in the wound until activated repair cells come to the genes. Cellular selectivity arises naturally. Something that was "really novel and surprising happened," Abbott said. Regular tissue just "sits there and does its thing," but when injured, it "becomes incredibly active metabolically. Repair cells take up debris, for instance, to help the wound. This same activity leads to very high uptake of delivered genes.

"Using GAM to deliver genes into an osteotomy site in animals, we found, 30 days later, that up to 50 percent of available cells took up the gene," he said. "In addition, by transfecting repair cells with the gene for a therapeutic protein, the protein can be produced throughout the entire healing period, significantly accelerating the process. It also is a more consistent day-to-day protein level, which is similar to natural body conditions."

Selective Genetics has an issued patent for gene therapy using a matrix, said Abbott. "We own this sandbox."

To promote tissue and cell regeneration, Selective also uses fibroblast growth factor (FGF-2) linked to plasmid DNA or to viral vectors as a targeting agent, a technology developed by Prizm. FGF-2 interacts with its high-affinity receptors with the highest affinity found in the human body. Most importantly, these receptors are found almost exclusively on tissue repair cells or malignancy. It was this overlap of the GAM and FGF-2 technologies in the area of tissue repair that created the rationale for Matrigen's merger with Prizm to form Selective.

Another aspect of the company's focus on site-specific gene delivery is its development of gene-containing polymers, making it one of the first companies to show the delivery of gene therapeutics from coatings on minimally invasive medical devices such as sutures, stents or orthopedic screws, creating a new class of site-specific gene therapy products known as DNA devices.

Abbott said three products are scheduled to begin clinical trials during the next year. The first is a bone repair product that will serve as a replacement for bone grafts and be used for treating complex fractures and hip fractures in osteoporosis. The second product will be for the treatment of diabetic ulcers, and a third, using FGF-2 targeting, will be for treating cancer.

Although privately funded, Selective Genetics is in serious talks with potential partners. Discussions have reached the stage of "exchanging term sheets," Abbott said, "so we are optimistic about having our first corporate partner soon." *