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Attenuated, replication-competent herpes simplex virus type 1 mutant G207: safety evaluation in mice
P Sundaresan1, W D Hunter, R L Martuza
1Molecular Neurosurgery Laboratory, Department of Neurosurgery, Georgetown University Medical Center, Washington, D.C. 20007, USA.
Journal of Virology
|March 23, 2000
Summary
G207, a modified herpes simplex virus type 1 (HSV-1) vector, demonstrated safety in mice. This oncolytic virus showed no adverse effects even at high doses, supporting its potential for cancer therapy.
Area of Science:
- Virology
- Oncology
- Gene Therapy
Background:
- Herpes simplex virus type 1 (HSV-1) mutants with reduced neurovirulence are explored for cancer treatment.
- G207 is a replication-competent HSV-1 vector engineered with multiple mutations.
Purpose of the Study:
- To evaluate the safety profile of the G207 HSV-1 vector in a murine model.
- To assess the neurovirulence and potential for latency of G207 compared to wild-type HSV-1.
Main Methods:
- Mice were inoculated with varying doses of G207 or wild-type HSV-1 strains (KOS, F) via intracerebral, intracerebroventricular, or intrahepatic routes.
- Survival rates, clinical symptoms, LacZ gene expression, and viral DNA detection (PCR) were monitored.
- Reactivation from latency was assessed by challenging mice with G207 after prior HSV-1 infection.
Main Results:
- G207 showed significantly reduced toxicity compared to wild-type HSV-1 across all inoculation routes.
- Mice receiving high doses of G207 survived long-term with no apparent disease.
- While G207 DNA was detectable for weeks, infectious virus was cleared rapidly, and no reactivation occurred in a latency model.
Conclusions:
- G207 exhibits a favorable safety profile in mice, even at doses effective for tumor treatment.
- The attenuated nature of G207 minimizes neurovirulence and the risk of reactivation, supporting its therapeutic potential.