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Newborn liver gene transfer by an HIV-2-based lentiviral vector

Gene Therapy volume 12, pages 803–814 (2005)Cite this article

Abstract

Newborn gene therapy, because it can prevent the damage caused by the onset of a disease, deserves specific attention. To evaluate gene transfer in tissues of newborn mice, we used a human immunodeficiency virus (HIV)-2 based lentiviral vector pseudotyped with vesicular stomatitis virus G glycoprotein expressing the green fluorescent protein reporter gene under the control of the cytomegalovirus promoter. We found that very low doses of HIV-2 could infect and be expressed in newborn mice. Under these conditions, the virus was preferentially expressed in the liver and hepatocytes were the predominant target. The treatment was not toxic, the infected liver cells proliferated and the transduced gene was stably expressed. Adult mice could be infected by HIV-2, but the vector was detected in the liver only utilizing the sensitive method of polymerase chain reaction coupled with Southern blot. Direct comparison between newborn and adult recipients demonstrated a much greater efficiency of liver transduction in the newborn mouse. These results indicate that the combination of early intervention and low multiplicity of infection may be a strategy for preferentially and efficiently targeting newborn liver for gene therapy applications.

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Acknowledgements

We thank Dr Sandra Pastorino for providing Mirò cell line, Amleto De Santanna (DIMES, Genova, Italy) for the excellent technical support, Dr Simonetta Astigiano (IST, Genova, Italy) and Dr Anna Favre (G Gaslini Institute, Genova, Italy) for helpful suggestions and Ms Chantal Dabizzi for secretarial assistance. This work was supported by grants from the Italian Association for Cancer Research (AIRC), Fondazione Italiana per la Lotta al Neuroblastoma, Associazione Italiana Glicogenosi, Italian Health Ministry, Compagnia di San Paolo (Torino) and COFIN-MIUR (2002).

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Authors and Affiliations

  1. Laboratory of Molecular Biology, G Gaslini Institute, Genova, Italy

    B Salani, P Damonte, A Zingone, A Eva & L Varesio

  2. Department of Oncology, Biology and Genetic, University of Genova/IST, Genova, Italy

    O Barbieri

  3. Section on Cellular Differentiation, National Institutes of Health, Rockville Pike, Bethesda, MD, USA

    J Y Chou

  4. Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA

    J D'Costa & S K Arya

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Salani, B., Damonte, P., Zingone, A. et al. Newborn liver gene transfer by an HIV-2-based lentiviral vector. Gene Ther 12, 803–814 (2005). https://doi.org/10.1038/sj.gt.3302473

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