THE nerve-destroying poliovirus may one day be an unlikely saviour for people
who suffer from nerve damage or neural diseases. Modified polioviruses can
deliver genes specifically to motor neurons in the brain and spinal cord,
studies in the US show.
Casey Morrow and his colleagues at the University of Alabama in Birmingham
have altered the virus鈥檚 genes to code for therapeutic proteins instead of coat
proteins. Viruses that can鈥檛 make coat proteins鈥攌nown as
replicons鈥攃an enter cells, but still cannot replicate and spread to other
cells. 鈥淲e anticipate using replicons to produce a variety of therapeutic
proteins delivered specifically to motor neurons,鈥 says Morrow.
To show the method works, Morrow鈥檚 team injected replicons into the spinal
cords of genetically engineered mice that have receptors for poliovirus. Mice
given a gene for a protein that causes nerve inflammation suffered loss of
coordination, for example, whereas mice given replicons that coded for a
harmless protein showed no ill effects.
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The effects were only temporary, however, peaking after about 10 hours. This
is because, unlike most gene delivery systems, the replicon genes do not become
a permanent part of a cell鈥檚 genome. Instead, the added genes break down after
about three days. 鈥淚 believe this is a benefit, allowing us control of the time
and level of protein expression not available in other gene therapy systems,鈥
Morrow explains.
While some may question the use of such a deadly virus, Ray Sanders of the
World Health Organization鈥檚 polio laboratory network is not concerned. 鈥淭he coat
protein defines a poliovirus. Without it, it鈥檚 not a virus,鈥 he explains.
鈥淥ur goals are in concert with the WHO鈥檚 effort to eradicate poliovirus,鈥
says Morrow. 鈥淭here will be no poliovirus in our replicon preparations.鈥
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Source:
Nature Biotechnology (vol 18, p 964)