Development of Truncated Malarial Var2CSA-Displaying Baculovirus Vectors and Their Gene Delivery Efficiency in HepG2 Cells.

Var2CSA, a member of the Plasmodium falciparum erythrocyte membrane protein (PfEMP) family, specifically binds to various human cancer cells through oncofetal chondroitin sulfate (ofCS) expressed on cell surfaces. This unique binding property has raised considerable expectations for the application of var2CSA in cancer-targeted diagnostics and therapies. Baculovirus vectors, known for their safety compared with other viral vectors, possess the ability to introduce genes into human cancer cells. We previously constructed a baculovirus expressing var2CSA containing DBL1X-DBL3X domains (var2CSA-type baculovirus) and demonstrated enhanced gene transduction efficiency in cancer cells. In the present study, we sought to further improve gene delivery by generating two truncated var2CSA constructs: rVAR2 (DBL1X-ID2a) and ID1-DBL2Xb. The rVAR2 was successfully expressed in purified budded virions, whereas the ID1-DBL2Xb showed no detectable expression in budded virions due to very low protein levels in insect Sf9 cells. Functional evaluation in HepG2 hepatocellular carcinoma cells revealed that rVAR2-type baculovirus exhibited significantly higher gene delivery efficiency than the var2CSA-type baculovirus. These findings suggest that rVAR2-expressing baculovirus represents a promising tool for cancer gene therapy, where enhanced gene delivery efficiency is highly desirable.