Fledgling gene therapy company Avigen has just licensed ahuman gene for multidrug resistance that it intends to use withits novel virus vectors as a therapy for patients undergoingchemotherapy.

Avigen announced today that it has received the exclusive,worldwide rights to the multidrug resistance (MDR) gene thatwas developed by researchers Susan Cole and Roger Deeley atQueen's University in Kingston, Ontario.

PARTEQ, the technology transfer arm of Queen's University,licensed the gene to Avigen for use with its adeno-associatedvirus (AAV) vectors. Avigen will pay PARTEQ a one-time issuefee for the license, as well as milestone and maintenancepayments and a royalty based on net sales of productsdeveloped with the licensed technology.

Researchers at the Canadian university first isolated the MRPgene (for which a patent application is pending) from humanlung cancer cells, explained Wanda deVlaminck, Avigen's vicepresident of regulatory affairs.

"They actually found increased levels of the protein and thenlooked for the gene expressing that protein," she said. The MRPprotein, in fact, is a member of a superfamily of energy-dependent transport proteins that may function as a pump,ridding cells of toxic substances.

Increased levels of MRP have been found in a number ofdifferent multidrug resistant cancer cell types, and there'sscientific evidence that MRP genes turn on when toxic agentsare present. In fact, one chemotherapy drug known to causetheir expression is doxorubicin, according to deVlaminck.

Interestingly, many of the large pharmaceutical companies thatmake chemotherapy drugs have been "looking for ways to turnoff the pump" that purges cells of toxic substances, deVlaminckexplained. "But for gene therapy, where we want the patient tobe able to tolerate higher doses of drugs, we want to turn onthe pump (gene)," she continued.

The goal is to render the patient's bone marrow cells highlyresistant to chemotherapy drugs by introducing into them theMDR gene via Avigen's AAV vector system. "We're enhancingthe resistance of a subset of normal cells" so they can survivethe chemotherapy intended to wipe out cancerous ones,deVlaminck told BioWorld. "We're targeting the bone marrowin types of cancers that don't involve the bone marrow."

Avigen of Alameda, Calif., envisions using its adeno-associatedvirus vectors to transfect a patient's cells and then inject thosecells back into the patient. In many gene therapy protocols, apatient's cells, once removed, have to be cultured for extendedperiods of time before they can be transfected; with AAVvectors, "you don't have to get the cells to replicate to take upthe (foreign) gene sequence," deVlaminck said. This means thewhole gene therapy procedure could be done fairly quickly.

-- Jennifer Van Brunt Senior Editor

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