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  • Original Article
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PEGylated helper-dependent adenoviral vector expressing human Apo A-I for gene therapy in LDLR-deficient mice

Gene Therapy volume 20, pages 1124–1130 (2013)Cite this article

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A Corrigendum to this article was published on 05 December 2013

This article has been updated

Abstract

Helper-dependent adenoviral (HD-Ad) vectors have great potential for gene therapy applications; however, their administration induces acute toxicity that impairs safe clinical applications. We previously observed that PEGylation of HD-Ad vectors strongly reduces the acute response in murine and primate models. To evaluate whether PEGylated HD-Ad vectors combine reduced toxicity with the correction of pathological phenotypes, we administered an HD-Ad vector expressing the human apolipoprotein A-I (hApoA-I) to low-density lipoprotein (LDL)-receptor-deficient mice (a model for familial hypercholesterolemia) fed a high-cholesterol diet. Mice were treated with high doses of HD-Ad-expressing apo A-I or its PEGylated version. Twelve weeks later, LDL levels were lower and high-density lipoprotein (HDL) levels higher in mice treated with either of the vectors than in untreated mice. After terminal killing, the areas of atherosclerotic plaques were much smaller in the vector-treated mice than in the control animals. Moreover, the increase in pro-inflammatory cytokines was lower and consequently the toxicity profile better in mice treated with PEGylated vector than in mice treated with the unmodified vector. This finding indicates that the reduction in toxicity resulting from PEGylation of HD-Ad vectors does not impair the correction of pathological phenotypes. It also supports the clinical potential of these vectors for the correction of genetic diseases.

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  • 05 December 2013

    This article has been corrected since online publication and a corrigendum is also printed in this issue

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Acknowledgements

This work was supported by the Telethon grant GGP04039, and from MIUR, project PRIN protocol number 2004069479_004. We thank Jean Ann Gilder (Scientific Communication srl, Naples, Italy) for revising and editing the text.

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Authors and Affiliations

  1. CEINGE-Biotecnologie Avanzate, Napoli, Italy

    E Leggiero, D Astone, V Cerullo, B Lombardo, L Sacchetti, F Salvatore & L Pastore

  2. Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università di Napoli ‘Federico II’, Napoli, Italy

    E Leggiero, D Astone, V Cerullo, B Lombardo, C Mazzaccara, L Sacchetti & L Pastore

  3. Division of Biopharmaceutics and Pharmacokinetics, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland

    V Cerullo

  4. Fondazione IRCCS SDN, Istituto di Ricerca Diagnostica e Nucleare, Napoli, Italy

    G Labruna & F Salvatore

  5. Division of Pharmaceutics, College of Pharmacy, The University of Texas at Austin, Austin, TX, USA

    M Croyle

  6. Institute of Cellular and Molecular Biology, The University of Texas at Austin, Austin, TX, USA

    M Croyle

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  1. E Leggiero
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Correspondence to L Pastore.

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Leggiero, E., Astone, D., Cerullo, V. et al. PEGylated helper-dependent adenoviral vector expressing human Apo A-I for gene therapy in LDLR-deficient mice. Gene Ther 20, 1124–1130 (2013). https://doi.org/10.1038/gt.2013.38

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