SAN FRANCISCO - Add hepatitis B to the list
of diseases alongside AIDS, herpes and the common cold researchers
are using in attempts to create medicines in the sometimes rocky
gene therapy research field.
On Sunday, a scientific team of 12 Japanese and Belgium
researchers reported it had some success in using a small molecule
produced by the hepatitis B virus to temporarily treat hemophiliac
mice.
The researchers said their technique more narrowly focuses where
the inserted genes land after being injected in the body than the
other viruses. Their work was published online Sunday by the journal
Nature Biotechnology.
Gene therapy researchers seek to fight genetic disorders by
replacing bad genes with functional ones. One of the biggest hurdles
in the field is how to deliver the genetic payload into the desired
cells without creating other health problems for the patient.
Many researchers are working to replace the lethal genes of
viruses such as HIV with beneficial ones and injecting them into the
ill. But such engineered viruses sometimes drop their good genes
into bad spots in cells, which is what happened recently to two boys
who got leukemia after being successfully treated for the immune
disorder commonly called "bubble boy" disease.
The researchers in their report said their technique is more
focused than others because hepatitis B attacks only liver cells,
while other viruses have the potential of entering a wide variety of
cells.
The researchers aren't using the hepatitis B virus itself, but
instead are inserting disease-fighting genes into "nanoparticles"
produced by the virus. Still, those "nanoparticles" carrying
blood-clotting genes inserted by the researchers dumped their
genetic payload almost exclusively in the liver.
The mice produced measurable amounts of blood clotting proteins
for about 40 days, the researchers reported.
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 a publicly charged topic since the 1999
death of 18-year-old Jesse Gelsinger, who was given a different type
of gene therapy for another disease.
French researchers last year rejuvenated the field when they
reported gene therapy cured four boys of severe combined
immunodeficiency, or SCIDs, and better known as "bubble boy
disease." But the excitement was tempered months later because the
inserted genes that cured the SCIDS also caused two of the boys to
get sick with leukemia.
The researchers said Sunday their technique may better protect
against unintended consequences.
"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."
Still, Kay said the latest work had limitations, highlighted by
the fact the gene therapy stopped working in the mice after a brief
period. Continued injections of the new genes 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?"
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On the Net:
Nature Biotechnology:
http://www.nature.com/nbt
Kay's lab:
http://www.stanford.edu/group/kaylab/
Verma's lab:
http://www.salk.edu/faculty/faculty/details.php?id54