Malaria sporozoite protein expression enhances baculovirus-mediated gene transfer to hepatocytes.

Abstract

Baculovirus vector (BV) is able to transduce foreign genes into mammalian cells efficiently and safely by incorporating a mammalian promoter. In the present study, we tailored the surface proteins expressed by malaria sporozoites to enhance hepatocyte transduction. Sporozoites infect hepatocytes within minutes of initial entry into the blood circulation. Infectivity and hepatocyte-specific selectivity are mediated by the interplay between hepatocytes and sporozoite surface proteins. The circumsporozoite protein (CSP) and the thrombospondin-related anonymous protein (TRAP) bind to the heparan sulfate proteoglycan on the hepatocyte surface and contribute to sporozoite infection and hepatocyte selectivity. BVs displaying an ectodomain consisting of three different CSP variants (full-length, N-terminal and C-terminal) or TRAP on the virus envelope were constructed, and the resulting in vitro hepatocyte transduction efficiency was evaluated. We demonstrated improved hepatocyte transduction efficiency in BVs expressing CSP or TRAP ectodomains compared to BVs without malaria surface proteins. In addition, gene transduction efficiencies for BVs displaying CSP or TRAP are higher than those expressing the preS1 antigen of the hepatitis B virus. BVs expressing CSP or TRAP in the ectodomain could represent a promising hepatocyte-specific gene delivery methodology. Copyright © 2016 John Wiley & Sons, Ltd.