PRIMATE SCIENCE RESEARCH HIGHLIGHT
Aug. 25, 1999
"Gene therapy in monkeys may help people with anemia"
(Courtesy the Institute for Human Gene Therapy, University of Pennsylvania)

People with anemia may soon have a more efficient and effective way of
boosting their red blood cells counts, thanks to some recent gene therapy
successes in rhesus monkeys.

Scientists at the University of Pennsylvania's Institute for Human Gene
Therapy have successfully injected into the skeletal muscle of six rhesus
monkeys a human-derived gene that codes for a protein hormone called
erythropoietin (Epo). Not only does this hormone prompt the bone marrow to
produce more red blood cells, but the gene that triggers it can be switched
on simply by giving the monkey a pill.

Institute Director James Wilson, M.D., Ph.D., and his team used a small
adeno-associated virus to deliver the Epo gene into the monkeys' skeletal
muscle cells. The disabled virus, which does not trip the body's immune
system, has only two genes. When both are removed, only the virus's head
and tail remain to transport the therapeutic genes into target cells.

Wilson's team also inserted two other genes that work together to "switch
on" the therapeutic gene only in the presence of the drug rapamycin. This
means that the monkeys can take a pill just once a month instead of getting
repeated injections of Epo. The delivery system has also proven successful
in mice. In these animals, administration of rapamycin resulted in 200-fold
induction of plasma Epo. Furthermore, the combination gene delivery and
drug trigger system maintained stable levels of red blood cells for six
months. The researchers have so far observed similar results in the monkeys
for at least three months. (At the time this highlight went to press, they
had expanded their work in nonhuman primates to include eight additional
animals.)

People with low red blood cell blood counts now receive regular Epo
injections. Dr. Wilson and his colleagues now believe that a better therapy
might be to insert the Epo gene into patients' muscle cells just once, and
then switch it on every month or so with the pill rapamycin.

###

Reference:

Ye X., V.M. Rivera, P. Zoltick, F. Cerasoli Jr., M.A. Schnell, G. Gao, J.V.
Hughes, M. Gilman, and J.M. Wilson. 1999. Regulated delivery of therapeutic
proteins after in vivo somatic cell gene transfer. Science. Jan
1;283(5398):88-91.


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Primate-Science Research Highlights appears every other week and focuses
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