Preferential Gene Transfer of Lentiviral Vectors to Liver-Derived Cells, Using a Hepatitis B Peptide Displayed on GP64

One of the problems that limit the efficiency of viral gene therapy is the lack of specificity of viral particle binding. The development of techniques to target viral particles to specific cell types is therefore important. Because GP64 can efficiently pseudotype lentiviral vectors, we investigated the possibility of using GP64 for lentiviral vector particle targeting. A peptide derived from the hepatitis B virus (HBV) PreS1 protein, with known affinity for an unidentified receptor expressed on hepatocytes, was inserted at amino acid position 278 of the GP64 protein (PreS1-GP64). The GP64 and PreS1-GP64 proteins were expressed and incorporated into lentiviral particles at comparable levels. Flow cytometry measurements confirmed surface display of the PreS1 peptide. The highest titers of PreS1-GP64-pseudotyped lentiviral vectors were observed on liver-derived cell lines. Gene transfer of PreS1-GP64 lentiviral vectors was inhibited by coincubation with an antibody directed against the PreS1 peptide. These data suggest that the PreS1 peptide is involved in viral attachment to the cell surface. The insertion of targeting peptides into the GP64 envelope protein represents a potential approach for the targeting of lentiviral vectors to specific cell types.