Non-human papillomaviruses for gene delivery in vitro and in vivo.

Lea Bayer,Thomas Grunwald,Martin Müller,Gerd Hause,Jessica Gümpel,Robert D Burk

doi:10.1371/journal.pone.0198996

Abstract

Papillomavirus capsids are known to have the ability to package DNA plasmids and deliver them both in vitro and in vivo. Of all known papillomavirus types, human papillomaviruses (HPVs) are by far the most intensely studied. Although HPVs work well as gene transfer vectors, their use is limited as most individuals are exposed to this virus either through a HPV vaccination or natural infection. To circumvent these constraints, we produced pseudovirions (PsVs) of ten non-human papillomavirus types and tested their transduction efficiencies in vitro. PsVs based on Macaca fascicularis papillomavirus-11 and Puma concolor papillomavirus-1 were further tested in vivo. Intramuscular transduction by PsVs led to months-long expression of a reporter plasmid, indicating that PsVs have potential as gene delivery vectors.

Highlights

The transfer of nucleic acids for gene therapy or as genetic vaccines has several advantages, most importantly the rapid production, simple adaptation and high stability at ambient temperature of DNA
The aim of this study was to explore a range of non-human papillomaviruses (NHPVs) for their suitability as gene carriers
Cross-neutralization between different PV types is theoretically not expected, it remains to be elucidated in future studies to which degree cross-neutralization between antibodies developed by HPV- or NHPV-vaccinated individuals may restrict the gene transfer by NHPV PsVs

Summary

Introduction

The transfer of nucleic acids for gene therapy or as genetic vaccines has several advantages, most importantly the rapid production, simple adaptation and high stability at ambient temperature of DNA. While intramuscular injection of naked DNA leads to a reasonable cellular uptake and subsequent expression in rodents [2], larger animals—especially non-human primates—require additional stimuli to enhance the uptake of the plasmid DNA [3]. One of the most effective methods to enhance DNA-uptake is the use of electroporation [4,5].

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