UF to produce human gene therapy medicine

Bolstered by a new production director, additional staff and a sophisticated facility, the University of Florida will soon begin manufacturing high-quality gene therapy medicines that can be used in humans.

Richard O. Snyder, Ph.D., an assistant professor of molecular genetics and microbiology, was recruited from Harvard Medical School earlier this year to direct the multimillion-dollar endeavor. Snyder has worked in the fields of microbiology and genetics for over 15 years with a focus on adeno-associated virus or AAV. The virus can be modified to transport disease-specific corrective genes into selected tissues to provide therapeutic benefit. His work in both academia and the biotechnology industry has contributed to innovations in production and application of gene therapy for a variety of diseases.

Currently no academic institution produces a grade of AAV for use in people. Two biotechnology companies are the sole producers of human-grade AAV vectors that are in patient trials.

UF has a strong history with AAV. Some of the original work to understand the basic biology of the virus was performed at the university, where scientists also have worked to evaluate its safety and effectiveness for gene therapy. Recognizing the apparent harmlessness of the virus and engineering its special features into a gene transfer vector, Kenneth I. Berns, M.D., Ph.D., and Nicholas Muzyczka, Ph.D., pioneered the use of AAV for carrying reparative genes into the body. Berns is UF’s vice president for health affairs and dean of the College of Medicine. Muzyczka is the founding director of the university’s Powell Gene Therapy Center.

AAV is considered among the most promising vectors, and its use in gene therapy research is increasing nationwide. UF already produces the carrier vector for many research studies being conducted worldwide in tissue cultures and animals. Last year, UF’s vector core produced about 500 batches of AAV for researchers conducting investigations on a variety of disorders, including inherited forms of blindness, muscular dystrophy, obesity and Parkinson’s disease. UF researchers created the nation’s first benchmark supply of AAV, which scientists from across the country are using to compare the strengths of their own investigational vectors.

Under Snyder’s direction, the Human Applications Laboratory and Vector Core could begin manufacturing the clinical-grade AAV by late fall. The laboratory is a joint effort of the Powell Gene Therapy Center, UF’s Genetics Institute and the Evelyn F. and William L. McKnight Brain Institute of UF. Shands HealthCare is supplying staff for the team.

The Human Applications Laboratory occupies the fifth floor of the Brain Institute and was specially designed to meet stringent Food and Drug Administration requirements for producing biological materials that can be used in humans. The laboratories are being outfitted with new equipment. New manufacturing and quality-control personnel have been hired.

“We’re not out there trying to compete against drug companies. We’re trying to fulfill a role for early-stage trials in relatively rare disorders that are usually studied and treated in academic medical centers,” said Terence R. Flotte, M.D., a professor of pediatrics who directs UF’s Genetics Institute.

Initially, UF will produce the high-grade vector for a clinical trial of gene therapy for alpha-1-antitrypsin deficiency, a potentially fatal genetic disorder that causes early emphysema and severe liver disease. In the next five years, UF also plans to produce vectors to treat people with other diseases, including muscular dystrophy, Parkinson’s and the rare blinding disorder Leber congenital amaurosis.

“We have a very good chance to succeed given the high concentration of expertise at UF coupled with the broad support of university, charitable, state and federal institutions,” said Snyder, who will lead the effort to further develop the technology and methods needed to meet the increasing demand for gene transfer vectors such as AAV for research and patient applications. Eventually, the facility also will be used to produce other vectors and cell-based genetic therapies that can be used in a wide range of human applications, such as cancer and acquired disorders.

Snyder also will direct his own research laboratory, which will focus on expanding basic knowledge about the characteristics, makeup and processes of AAV. He will use the findings to improve vectors used to treat genetic diseases and optimize their production.