Redirecting retroviral tropism by insertion of hepatitis B virus PreS1 core peptide into the envelope

A potentially powerful approach for in vivo gene delivery is to target retroviral vectors to specific cells through interactions between cell surface receptors and appropriately engineered viral envelope proteins, but this has so far met with little success. We report here an attempt to target ecotropic MLV retroviral vectors to human cells infected by hepatitis B virus (HBV) through the interaction between the HBV PreS1 domain and the receptors on the cell surface. We examined 7 MLV chimeric envelope derivatives that contained either the HBV PreS1 peptide or PreS1 aa 21–47 segment (partial PreS1, pPreS1), which was inserted at various locations within the SU of the MoMLV Env. In addition to infecting host NIH 3T3 cells, some of pseudotyped viruses could transduce human cells. Our results demonstrate that short peptide ligands inserted at appropriate locations in the MLV envelope can selectively target retroviruses to human cells.