Related Experiment Video
Updated: Jun 15, 2026
Production and Purification of Baculovirus for Gene Therapy Application
Published on: April 9, 2018
Screening of complement inhibitors: shielded baculoviruses increase the safety and efficacy of gene delivery
Minna U Kaikkonen1, Antti I Maatta, Seppo Ylä-Herttuala
1Department of Biotechnology and Molecular Medicine, AI Virtanen Institute, University of Eastern Finland, Kuopio, Finland.
Abstract:
One of the major obstacles in the use of baculovirus vectors for in vivo gene transfer is the virus inactivation by serum complement. In this study, we investigated the effect of decay-accelerating factor (DAF), factor H (FH)-like protein-1 (FHL-1), C4b-binding protein (C4BP), and membrane cofactor protein (MCP) on protection of baculovirus vectors from the complement-mediated inactivation. Complement regulatory proteins were displayed on baculovirus surface as fusions to membrane anchor of the vesicular stomatitis virus-G (VSV-G) protein. This strategy resulted in abundant expression of recombinant proteins on the viral envelope while viral titers comparable to control virus were reached. The surface-modified vectors exhibited complement resistance in vitro, DAF showing the highest level of protection. Intraportal delivery of DAF-displaying baculovirus resulted in increased survival and enhanced gene expression in immunocompetent mice. Mice receiving DAF-displaying baculovirus also exhibited lower level of liver inflammation as evidenced by aspartate aminotransferase (AST). In line with this, macrophages treated with DAF baculovirus produced lower levels of inflammatory cytokines IL-1beta, IL-6, and IL-12p40 compared to control virus. These results suggest that DAF-display can protect the vector against complement inactivation but also reduce complement-mediated inflammation injury. In conclusion, complement shielded baculovirus vectors represent attractive tools for effective in vivo gene delivery.
Insights
Displaying decay-accelerating factor (DAF) on baculovirus vectors protects against serum complement inactivation. This strategy enhances in vivo gene transfer, improves survival, and reduces inflammation in mice.
Area of Science:
- Biotechnology
- Gene Therapy
- Immunology
Background:
- Baculovirus vectors are promising for in vivo gene transfer.
- Serum complement inactivates baculovirus vectors, limiting their therapeutic potential.
- Strategies are needed to shield baculovirus from complement-mediated attack.
Purpose of the Study:
- To evaluate the efficacy of complement regulatory proteins in protecting baculovirus vectors.
- To investigate the impact of surface-displayed proteins on vector function and immunogenicity.
- To assess the potential of complement-resistant baculovirus for enhanced gene delivery in vivo.
Main Methods:
- Complement regulatory proteins (DAF, FH-like protein-1, C4b-binding protein, membrane cofactor protein) were fused to the VSV-G protein anchor.
- Recombinant proteins were displayed on the baculovirus surface.
- Complement resistance was tested in vitro.
- In vivo gene transfer, survival, and liver inflammation were assessed in mice following intraportal delivery.
Main Results:
- Surface display of complement regulatory proteins conferred resistance to complement-mediated inactivation.
- Decay-accelerating factor (DAF) provided the highest level of protection.
- DAF-displaying baculovirus enhanced gene expression and survival in immunocompetent mice.
- DAF-modified vectors reduced liver inflammation and inflammatory cytokine production.
Conclusions:
- Surface display of DAF effectively shields baculovirus vectors from complement inactivation.
- DAF-display enhances in vivo gene delivery efficiency and reduces vector-induced inflammation.
- Complement-shielded baculovirus vectors are promising tools for effective in vivo gene therapy.
