By Mary Welch
Newly formed Replicor Inc. is dedicated to discovering and developing applications of technologies based on the regulation of DNA replication.
"We are a typical university spin-off," said Jean-Marc Juteau, chief executive officer. "We have three scientists from McGill University and myself. We subcontract lab space from McGill but next year we plan to be installed in our own laboratories. Yes, we are part of the hotbed of high technology that is happening in Montreal."
Replicor received $304,670 (C$450,000) in initial seed money from the venture capital firm, T2C2/Bio, based in Montreal. Limited partners of T2C2 are Sofinov, Business Development Bank of Canada, Canadian Medical Discoveries Fund Inc., and Societe Innovatech du Grand Montreal, all of Montreal. The company received another $101,560 from other sources.
"Montreal biotech certainly is not the size of the Boston area or California, but it is really active," Juteau said. "We have two big universities and research centers, and there is a lot of money here. There is a lot of venture capital money as well as good tax incentives. They are very, very good."
Juteau estimated a start-up company could receive 60 percent to 70 percent of its research and development costs from the government. "They are called tax credits but it is not so much a credit," he said. "It is a very real check. If you are a profitable company, you pay less taxes. And, of course, we all want to be like BioChem Pharma [Inc., of Laval, Quebec]. They are our influence, so to speak."
Juteau formerly was in charge of technology promotion in the biomedical area at Montreal-based McGill. The other three founders are scientists at McGill: Gerald Price, a professor of medicine and oncology; Maria Zannis-Hadjopoulos, a professor of medicine, biochemistry and oncology; and Irving Wainer, an adjunct professor of oncology. Wainer also is a full professor and head of the Washington-based Georgetown University Bioanalytical Center.
The company, which began operations in March, has three technology platforms: origin of replication consensus for gene therapy, modulation of cell division, and drug discovery.
"The core of the company is our origin of replication technology," Juteau said. The scientists have identified the mammalian origin of replication consensus, which consists of a 36-base pair piece of DNA. This sequence's functions include binding the proteins that initiate replication and, when ligated to any foreign DNA, permit replication in the cell.
"This very small piece of DNA is the origin of chromosome replication," he explained. "We found it. Presently nothing in the world like this exists. We tried to protect all the possibilities in our patents."
Currently, vectors being used in gene therapy cannot replicate themselves using only the cell machinery, he said.
"The benefit is that we can create very easily a new generation of vectors for the expression of genes," Juteau said. "And these vectors can be used in gene therapy, transgenics and other applications. We have produced stable plasmid vectors in mammalian cells without integration in the chromosome. Presently, when you try to express a gene on a plasmid, you can only do transient expression. We eventually hope to create artificial chromosomes with self-replication and segregation."
The second technology platform is the modulation of cell division. "It revolves around identifying the protein that is critical for the start of DNA replication and small molecules modulating DNA replication," Juteau said. "We have shown that we can stop DNA replication, stopping cell division."
The company has stopped cell division in in vitro models. The potential is that therapeutic agents can be developed against abnormal cell proliferation diseases such as cancer and inflammatory disorders. Another application is to possibly enhance DNA replication, which could lead to the development of compounds for up-regulating the DNA. Major uses would be tissue repair and organ regeneration as well as the increased expression of recombinant proteins.
The third platform allows the company to test compounds stimulating or inhibiting DNA replication, with one application being the ability to find the best molecular design for a drug.
"Our technology uses an in vitro human DNA replication system and mammalian DNA origins as controlling elements, permitting testing of compounds stimulating or inhibiting DNA replication," Juteau said. "The advantage, of course, is that the direct effect on DNA replication can be easily valued."
Although still young, the company's technology already has attracted the attention of some potential licensing partners. "We do not want just to be an agent for the technology. We want to work as a developer," Juteau said. "We want to work with the 'Big Ones' in the business. Of course, we are also interested in licensing. In fact, our work has created a lot of interest. Companies are coming to Montreal to talk to us."
Replicor, which currently has five employees, will be seeking more financial infusions starting next year, even if licensing deals come through soon. "We have a lot of technology and a lot of plans," he said. "We intend to grow and become a player internationally."