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Reducing cytotoxicity induced by Sindbis viral vectors
1Department of PathologyKaplan Cancer Center, New York University Medical Center, 550 First Avenue, New York, New York 10016, USA.
Molecular Genetics and Metabolism
|May 18, 1999
Summary
Researchers engineered Sindbis virus vectors to express human bcl-2, significantly reducing virus-induced cell death. This advancement in gene therapy vectors shows promise for more persistent viral infections.
Area of Science:
- Molecular Biology
- Virology
- Gene Therapy
Background:
- Sindbis virus is a potential gene therapy vector.
- Chimeric Sindbis virus vectors offer cell-specific targeting.
- Sindbis virus infection induces apoptosis, limiting its use.
Purpose of the Study:
- To investigate the role of bcl-2 expression in mitigating Sindbis virus-induced apoptosis.
- To develop a Sindbis virus vector expressing human bcl-2 and lacZ for gene therapy applications.
Main Methods:
- Construction of a chimeric Sindbis virus vector (SinRep/lacZ/bcl-2/DH-BB) expressing human bcl-2 and lacZ.
- Infection of BHK cells with the engineered vector and wild-type Sindbis virus.
- Assessment of cell proliferation and apoptosis levels post-infection.
Main Results:
- The engineered SinRep/lacZ/bcl-2/DH-BB vector demonstrated a marked reduction in apoptosis in infected BHK cells compared to wild-type Sindbis virus.
- Cell proliferation in BHK cells infected with the bcl-2 expressing vector was significantly higher (55% at 2 days, 40% at 3 days) than with wild-type virus (26% at 2 days, 7% at 3 days).
Conclusions:
- bcl-2 expression can effectively reduce Sindbis virus-induced apoptosis in infected cells.
- Further modifications of Sindbis virus vectors may be necessary to completely eliminate apoptosis for enhanced gene therapy utility.