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Treatment
> Gene
Therapy
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PNAS, April 4, 2006, vol. 103, no. 14.
5508-5513; Published online before print March 22, 2006,
10.1073/pnas.0601258103
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Abstract |
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Construction and properties of a
herpes simplex virus 1 designed to enter cells solely via the IL-13α2
receptor
Guoying Zhou, and Bernard
Roizman*
The Marjorie B. Kovler Viral
Oncology Laboratories, University of Chicago, 910 East 58th Street,
Chicago, IL 60637. -- *To whom correspondence should be addressed.
E-mail: bernard.roizman@bsd.uchicago.edu. -- Contributed
by Bernard Roizman, February 14, 2006. -- Author contributions: G.Z.
and B.R. designed research; G.Z. performed research; G.Z.
and B.R. analyzed data; and B.R. wrote the paper. --
Conflict of interest statement: No conflicts declared.
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Current design of genetically engineered
viruses for selective destruction of cancer cells is based
on the observation that attenuated viruses replicate better
in tumor cells than in normal cells.
The ideal virus, however, is one that can infect only cancer
cells by virtue of altered host range.
Such a virus can be made more robust than the highly
attenuated viruses used in clinical trials.
Earlier, we reported the construction of a recombinant
herpes simplex virus 1 (R5111) in which the capacity to
bind heparan sulfate was disabled and which contained a chimeric IL-13-glycoprotein
D that enabled the virus to infect cells expressing the
IL-13α2 receptor (IL-13Rα2) commonly found on
the surface of malignant glioblastomas or high-grade
astrocytomas.
In the earlier report, we showed that the recombinant R5111 was
able to enter and infect cells via the interaction of the chimeric
glycoprotein D with IL-13Rα2 but that the virus retained
the capacity to bind and replicate in cells expressing the
natural viral receptors HveA or nectin-1.
Here, we report the construction of a recombinant virus
(R5141) that can only enter and replicate in cells that
express the IL-13Rα2.
The recombinant R5141 does not depend on endocytosis to
infect cells.
It does not infect cells expressing HveA or nectin-1
receptors or cells expressing IL-13Rα2 that had
been exposed to soluble IL-13 before infection.
The studies described here show that the host range of herpes simplex
viruses can be altered by genetic manipulation to specifically target
cancer cells.
Keywords: glycoprotein D;
HveA; malignant glioblastoma; nectin-1
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© 2006 by The National Academy of
Sciences of the USA
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 Abstract
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