WALTHAM, Mass. -- Harvard University has grantedCollaborative Research Inc. an exclusive, worldwide license tocommercialize its computer-assisted multiplex DNA sequencingtechnology.

Collaborative Research (CRI) acquired the commercial R&Drights to two issued U.S. patents (plus a third one pending) heldby molecular geneticist George Church of the university'sHoward Hughes Medical Institute.

Joyce Brinton, director of Harvard's Office for Technology andTrademark Licensing, and Robert Hennessey, CRI's presidentand chief executive officer, signed the agreement two weeksago and announced it today.

"Multiplex sequencing will be the core enabling technologywithin our company over the next several years," Hennesseytold BioWorld. He cited its potential to generate rapid, high-efficiency processes leading to drug discovery, vaccines,diagnostics and other commercial applications.

"To the best of our knowledge, this multiplexing is about asgood as any of the other sequencing technologies that areavailable, and in some ways it may even be superior," saidOrrie Friedman, founder and chairman of the Waltham, Mass.,company. "I think the ABI (Applied Biosystems Inc.) automatedDNA sequencer is more efficient for sequencing smallfragments, but for large-scale sequencing, this computer-assisted multiplexing is a very attractive technology. It puts usin a pretty special position in this whole field."

"The multiplex concept is the mixing together of many DNAsamples, their processing and final de-coding," explained CRI'ssenior vice president of research and development, GeraldVovis. "We think the multiplex method will also be a powerfulway of sequencing the human genome."

Having unraveled by multiplex one DNA fragment in the rangeof 50 kilobases as a modest demonstrator model, Vovis said:"We have had no problem, even though we found 34 repetitiveelements. In fact, it's more difficult to sequence Mycobacteriumtuberculosis than Homo sapiens because the guanine-cytosinecontent is higher in the bacteria."

In fact, the current target of the company's large-scalesequencing program is the genome of M. tuberculosis, theorganism that causes tuberculosis. "The size of these pathogenicorganism genomes is in the range of 3 to 4 million bases," Vovissaid. "Thus, to get a representation of the entire genome is wellwithin our ability in a very short period of time."

He said he expects multiplexing to get bacterial sequencingeasily down to one genome a year on virtually any pathogenicorganism, such as those that cause sexually transmitteddiseases or strep infections, as well as thermophilic bacteria forindustry.

A three-year, $5 million grant from the National Center forHuman Genome Research currently supports CRI'smycobacteria project, which also includes sequencing M. leprae,the cause of leprosy. "The current Collaborative Research effortaddresses urgent medical problems with the new multiplexingtechnology, with enthusiastic support from the World HealthOrganization and the National Institutes of Health," said Church.

"In the year since CRI tackled the mycobacteria genomes, wehave identified over 600 full-length genes and sequenced over700,000 base pairs of the TB and leprosy organisms' DNA,"Vovis said. "These form the basis of a patent application wefiled this summer. Next year we're projecting to double thatthroughput, and redouble it the third year."

Vovis pointed out that "the license from Harvard is for themultiplex technology PP the process. Whatever genes come outwould, of course, have the commercial value. They would bethe candidates one would want to develop vaccines for or drugsagainst."

Among the M. tuberculosis genes already discovered "areseveral that may be ideal candidates for drug intervention, forthey appear to be involved in the bacterium's cell-wallsynthesis," Vovis said. "Mycobacteria distinguish themselves bythe composition of their cell wall."

CRI is pursuing several of these bacterial genes to see which, ifany, are vital to the survival of M. tuberculosis, Vovis said. Hewill try to determine whether knocking them out of theorganism's genome will harm their viability.

CRI's Hennessey is discussing commercial opportunitiesstemming from multiplex sequencing research with "a leadingpharmaceutical company we can't identify." He did confirm thatthe partnering hopeful is not Abbott Laboratories, with whichCRI signed a research agreement in July covering unspecifiedR&D activities.

CRI "is a public company with limited resources," saidHennessey. "It's not a secret that in addition to aggressivelypursuing dialogs with potential pharmaceutical partners, we'recurrently in touch with several dozen firms specialized inmiddle-market financing." His target is to raise some $5 million.

The company's cash position for fiscal year 1993 (ended Aug.31), was $3.9 million, with a monthly burn rate of $125,000,Hennessey told BioWorld.

Collaborative Research's stock (NASDAQ:CRIC) closedunchanged Wednesday at $1.75 a share.

-- David N. Leff Science Editor

(c) 1997 American Health Consultants. All rights reserved.