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Targeting human glioma cells using HSV-1 amplicon peptide display vector
1Laboratory of Cancer Gene Therapy, Division of Cellular and Molecular Research, Humprey Oei Institute of Cancer Research, National Cancer Centre, Singapore.
Gene Therapy
|October 9, 2009
Summary
Researchers modified herpes simplex virus type 1 (HSV-1) vectors to target glioma cells. By incorporating a glioma-specific peptide (MG11) into the viral envelope, they enhanced HSV-1 tropism and homing to human glioma cells.
Area of Science:
- Virology
- Oncology
- Biotechnology
Background:
- Herpes simplex virus type 1 (HSV-1) vectors are complex for targeting cell infections due to viral glycoprotein and host cell surface protein interactions.
- Modifying viral vectors is crucial for enhancing targeted delivery in therapeutic applications.
Purpose of the Study:
- To engineer HSV-1 amplicon vectors with enhanced tropism for human glioma cells.
- To investigate the potential of a glioma-specific peptide (MG11) for redirecting HSV-1 binding to glioma cells.
Main Methods:
- A human glioma-specific peptide sequence (MG11) was inserted into an HSV-1 amplicon vector, replacing the heparan sulfate-binding domain of glycoprotein C (gC).
- Modified MG11:gC envelope recombinant vectors were packaged into virions using a helper virus lacking gC.
- In vitro tropism assays on human glioma cells and in vivo homing studies in a xenograft glioma mouse model were performed.
Main Results:
- The modified HSV-1 recombinant virions exhibited increased tropism for human glioma cells compared to wild-type virions.
- Glioma-specific peptide (MG11) effectively blocked recombinant virion binding, indicating competition for shared cell surface receptors.
- Preferential homing of these engineered virions was observed in a xenograft glioma mouse model after intravascular delivery.
Conclusions:
- Incorporating the MG11 peptide sequence into HSV-1 virions redirects their binding tropism towards human gliomas.
- This strategy validates the potential of engineered HSV-1 vectors for targeted delivery to gliomas.
