Artificially envelopment of adenovirus (Ad) within lipid bilayers can decrease the immunogenicity and hepatoxicity properties of Ad in vivo. Unfortunately, this also results in a significant reduction of gene expression, maybe due to poor release of the Ad from its lipid envelope.We have explored the use of pH-sensitive DOPE:CHEMS envelopes for Ad and characterized these materials by TEM, AFM, dot blot, dynamic light scattering and zeta potential measurements. The enveloped viruses exhibited good stability at physiological pH but immediately collapsed and released naked virions at pH 5.5. We obtained comparable levels of gene expression to naked Ad in different cell lines. Furthermore, the intracellular trafficking with confocal laser scanning microscopy revealed that Cy3 labelled Ad enveloped in DOPE:CHEMS showed a uniform fluorescence distribution within the cytoplasm, indicating endosomal release of Ad. Finally, these pH-sensitive enveloped Ad were injected intratumoraly in nude mice showing similar levels of gene expression to naked Ad.

Efficient gene delivery using acid-responsive lipid envelopes for adenovirus

240th National Meeting (2010)

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