Researchers report gene therapy promise using piece of virus

SAN FRANCISCO -- Scientists have worked for years to harness the power that viruses have to invade cells, replacing unwanted elements of herpes and other viruses with disease-fighting genes in hopes the new genetic payload would correct a targeted illness.

Such genetic therapies have found limited success so far.

But a team of 12 Japanese and Belgian scientists says it has found promise with the hepatitis B virus, using it as a tool to temporarily treat hemophiliac mice.

The researchers reported Sunday in the online edition of the journal Nature Biotechnology that their technique -- using a small, hollow fragment of the hepatitis B virus -- enables the inserted genes to be more narrowly focused than other viral delivery systems.

Engineered viruses sometimes deliver good genes to bad places, setting unintended cellular changes in motion. That's what happened recently to two boys who got leukemia after being successfully treated for the immune disorder commonly called "bubble boy" disease.

Those other viruses have the potential of entering a wide variety of cells, but the researchers said in their report that their hepatitis B method targets only liver cells.

The researchers aren't using the whole hepatitis B virus, but instead are inserting disease-fighting genes inside "nanoparticles," tiny fragments of the virus.

Those nanoparticles dumped their genetic payload of blood-clotting genes almost exclusively in the liver.

Using that technique, the researchers said, their test produced measurable amounts of blood clotting proteins for about 40 days.

The nanoparticle is "a safe vehicle for delivering both genes and drugs," the researchers concluded. The lead author of the study was Tadanori Yamada of Osaka University.

Gene therapy has been controversial since the 1999 death of 18-year-old Jesse Gelsinger, who was given a different type of gene therapy for another disease at the University of Pennsylvania in Philadelphia. He developed an immune response to the virus being used.

French researchers rejuvenated the field last year when they reported curing four boys of severe combined immunodeficiency, or SCIDs, and better known as "bubble boy disease." But that excitement was tempered months later because some of the inserted genes that cured the SCIDS also ended up in the wrong place and caused two of the boys to develop leukemia.

The new technique may better protect against such unintended consequences, the researchers said Sunday.

"Delivery is the big issue in gene therapy," said Dr. Mark Kay, director of Stanford University's Human Gene Therapy Program." This is encouraging. It's the kind of stuff we need in the field."

However, Kay said the latest work had limitations, highlighted by the fact the gene therapy stopped working in the mice after a brief period. Injecting more of the gene-carrying virus will cause the body to build up resistance to the therapy, Kay said.

Another problem arises with the use of the hepatitis B virus because many people are vaccinated against the disease, said gene therapy scientist Inder Verma of the Salk Institute of Biological Studies. The vaccine will kill the therapy as well, Verma said.

"It's exciting and interesting," Verma said. "But now what?"

------

On the Net:

Nature Biotechnology: http://www.nature.com/nbt

Kay's lab: http://www.med.stanford.edu/kaylab/

Verma's lab: http://www.salk.edu/faculty/faculty/details.php?id54