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Gutless adenovirus: last-generation adenovirus for gene therapy

Abstract

Last-generation adenovirus vectors, also called helper-dependent or gutless adenovirus, are very attractive for gene therapy because the associated in vivo immune response is highly reduced compared to first- and second-generation adenovirus vectors, while maintaining high transduction efficiency and tropism. Nowadays, gutless adenovirus is administered in different organs, such as the liver, muscle or the central nervous system achieving high-level and long-term transgene expression in rodents and primates. However, as devoid of all viral coding regions, gutless vectors require viral proteins supplied in trans by a helper virus. To remove contamination by a helper virus from the final preparation, different systems based on the excision of the helper-packaging signal have been generated. Among them, Cre-loxP system is mostly used, although contamination levels still are 0.1–1% too high to be used in clinical trials. Recently developed strategies to avoid/reduce helper contamination were reviewed.

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Acknowledgements

We would like to acknowledge Dr Mercè Monfar for critically reading the manuscript. Our work is supported by MCYT-SAF2003-03256, Marató TV3-2002-031632 and Instituto de Salud Carlos III (C03/08). AB has a contract from the Ramon y Cajal Program (Ministerio Educación y Ciencia, Spain), and RA is a recipient of an FI-Generalitat fellowship.

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Alba, R., Bosch, A. & Chillon, M. Gutless adenovirus: last-generation adenovirus for gene therapy. Gene Ther 12 (Suppl 1), S18–S27 (2005). https://doi.org/10.1038/sj.gt.3302612

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Keywords

  • adenovirus
  • gutless
  • helper-dependent vectors
  • in vivo gene therapy

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