A small human virus that elicits no symptoms is the basis of anew gene therapy company that has just raised its first $2million in seed capital.

Formed by John Monahan, the former vice president ofresearch and development at Somatix Therapy Corp. ofAlameda, Calif., Avigen Inc. was incorporated last December inAlameda to focus on treatments for red blood cell disorderssuch as sickle cell anemia and thalassemias, as well as atreatment for AIDS and chemotherapy drug tolerance.

Instead of using more common retroviral vectors to introducegenes into patients with life-threatening diseases, the companyplans to use adeno-associated viruses, infective packets ofsingle-stranded DNA that were first isolated as a contaminantin a preparation of adenovirus, which causes the common cold.

About 85 percent of the population has been exposed to adeno-associated virus, or AAV, but it received little attentionbecause it does not cause disease, said geneticist Mimi Hancock,vice president of operations and development. She directed cellbiology programs at Somatix.

This obscure virus could be a "real wave of the future," addedWanda de Vlaminck, who became vice president of regulatoryaffairs at Avigen after holding a similar position at Somatix.

She said AAV seemed "more commercially viable" because itlacks several retrovirus drawbacks. Retroviruses integraterandomly into genetic material of cells and can disrupt criticalcell functions or incite tumors. They also cannot be injecteddirectly because they are unstable in blood, so a patient's cellsmust instead be genetically modified outside the body.

Adenoviruses have been approved for human gene transfertrials in cystic fibrosis, and may have gene transferapplications to the brain and other organs. However,adenovirus apparently doesn't become inserted in the cell'sDNA and may not be passed to daughter cells, which meanspatients might have to be redosed. Also, the patients mightdevelop neutralizing antibodies, Hancock said.

AAV, on the other hand, integrates "very specifically" into asingle location on chromosome 19, she said. Vectors made fromAAV apparently insert into one or two different, butpredictable and identifiable sites in the same chromosome, anoccurrence Hancock called a "wonderful advantage."

AAV is also stable in blood and can be directly injected intopatients.

The company licenses a patent on the AAV vector from theIndiana University School of Medicine, where it was developedby Arun Srivastava. Avigen is also licensing from The JohnsHopkins University School of Medicine a patent application onfusion proteins that interfere with replication of such virusesas HIV and hepatitis. The company is pursuing other licensesfor genes that confer resistance to cytotoxic agents and for genesequences, including antisense versions, de Vlaminck added.

The company's scientists are working with academiccollaborators, but will soon conduct research in rentedlaboratory space in Walnut Creek, Calif., while the companybuilds a 16,000-square-foot laboratory at the Harbor BayBusiness Park in Alameda, de Vlaminck said.

Avigen is focusing on finding animal models and producing invivo gene expression, de Vlaminck said. Hancock expectsAvigen may enter clinical trials in thalassemia and sickle cellanemia by the first quarter of 1995 with Avicell, a globin genedelivery and expression vector.

"This treatment has the potential to eliminate the symptoms ofthese diseases and significantly reduce the time and expense ofongoing patient care," Monahan said.

The company's second product under development, Aviase, isdesigned to protect patients infected with HIV from furtherinfection by causing any additional HIV produced in bonemarrow cells to self-destruct. Aviase encodes a viral proteinfused to a nuclease.

A third project is intended to aid chemotherapy patients byintroducing genes for cytotoxic drug resistance to normal bonemarrow cells. This therapy could protect bone marrow fromdamage and allow higher drug doses to be administered topatients, increasing their chance of survival.

The company was co-founded by a venture capital firm, TheCastle Group Ltd., which has four executives on Avigen's boardof directors.

Avigen's scientific advisory board is chaired by Kenneth Berns,chairman and professor of microbiology at Cornell MedicalCollege and former chairman of the Recombinant DNA AdvisoryCommittee of the National Institutes of Health. Berns conductedearly characterization of AAV.

Other scientific advisers are Richard Samulski, an associateprofessor of biological sciences at the University of Pittsburgh,who has pioneered development of AAV vectors, and Y.W. Kan,a professor of medicine at the University of California, SanFrancisco, who received the Lasker Award for Medicine in1991 for his study of sickle cell anemia and thalassemia.

-- Nancy Garcia Associate Editor

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

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