Poor intercellular transport and absence of enhanced antiproliferative activity after non-viral gene transfer of VP22-P53 or P53-VP22 fusions into p53 null cell lines in vitro or in vivo.

Background: The herpes simplex virus type 1 (HSV-1) VP22 protein has the property to mediate intercellular trafficking of heterologous proteins fused to its C- or N-terminus. We have previously shown improved delivery and enhanced therapeutic effect in vitro and in vivo with a P27-VP22 fusion protein. In this report, we were interested in studying the spread and biological activity of VP22 fused to the P53 tumor suppressor.

VP22-mediated and light-activated delivery of an anti-c-raf1 antisense oligonucleotide improves its activity after intratumoral injection in nude mice.

VP22, a protein of the herpes simplex virus tegument, can form complexes with fluorescein-labeled oligonucleotides. These particles, termed "Vectosomes," are efficiently taken up by cells and remain stable in the cell cytoplasm without any particular activity. Interestingly, these Vectosomes can be disrupted by light, which releases the antisense activity.