A curse turned into a cure?
The ancient scourge of polio could soon be tamed and turned into a beneficial agent for gene therapy of the spinal cord. One of the major challenges in gene therapy is to deliver a therapeutic gene to a particular cell type while avoiding introduction of the gene into other types of cells. The ability of poliovirus to specifically target neurons suggests that it could be an effective means of delivering genes to the nervous system in neurodegenerative conditions such as multiple sclerosis or spinal injuries and strokes. Now investigators have taken the first steps to engineer a poliovirus that does just that Nature Biotechnology (Vol 18, No. 9, September 2000).
To accomplish their task, Casey Morrow and colleagues first had to ensure that polio's notorious pathogenic properties could be ablated. They did this by removing from the poliovirus genome the gene sequence that encodes the proteins for the viral coat. Without the coat proteins, the virus cannot spread to other cells after it has accomplished its mission of delivering the therapeutic gene, which should attenuate its pathogenicity.
To test the effectiveness of the altered poliovirus to deliver foreign genes, Morrow's team had to generate mice containing the poliovirus receptor (PVR), to mimic the tissue makeup of humans. The spinal cord of each of these PVR mice was then injected with a poliovirus that contained a foreign gene-either for a harmless green fluorescent protein (GFP) or for a neurotoxic signaling molecule termed mouse tumor necrosis factor alpha (mTNF-a). As expected, the mTNF-a poliovirus induced severe neurological symptoms in the mice, whereas the GFP poliovirus appeared innocuous to the infected neurons. This suggested that the poliovirus itself was not toxic/pathogenic and that the attenuation approach had been successful.
A great deal of work remains before this system could ever be used in humans, but the results so far indicate that this deadly virus could one day be engineered for beneficial use.
Dr. Casey D. Morrow
University of Alabama at Birmingham
Department of Microbiology
619 Lyons-Harrison Research Building
1900 Seventh Ave South
Birmingham, AL 35294
Telephone #: 205.934.5705
Fax #: 205.934.1580
(News & Views)
Dr. Jacques Mallet
Hôpital de la Pitié Salpêtrière
LGN, UMR C 9923 DU CNRS
83, boulevard de l'Hopital
Telephone #: 33 +33 1 42 17 75 32
Fax #: +33 1 42 17 75 33
(C) Nature Biotechnology press release.
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