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Politically correct gene therapy? A “clean environment” improves gene delivery to the brain!

Gene Therapy volume 6, pages 463–464 (1999)Cite this article

The Holy Grail of neurological gene therapy is achieving long term transgene expression in the brain. Many neurological disorders evolve over 10–40 years. Most current gene therapy strategies, particularly those utilising adenoviral vectors, offer only shorter-term expression, although in some cases more persistent expression has been detected. This limits gene therapy applications to those diseases where relatively restricted gene delivery could still make a major therapeutic impact. Cancer gene therapy requires only short-term gene expression to achieve tumour cell killing. Thus, in neurology, direct virus-mediated gene transfer is mostly used to treat brain tumours,1,2 whereas neurodegenerative disorders which require long term therapy, have currently mainly been approached by engineered cell transplantation.3

Adenoviral vectors have been used for gene transfer into the brain, achieving a generally restricted gene transfer, both anatomically and temporally, although some important exceptions have been reported.4,5 However, gene delivery to the brain is prolonged when compared with delivery to peripheral organs like the liver. While in the liver, transgene expression is completely eliminated within 2–3 weeks, low level expression persists in the brain for substantially longer periods of time. Nevertheless, viral genomes can still be found in the liver as late as 6 months post-virus administration, indicating that even in the liver the inflammatory and immune cells may have limitations in physically eliminating cells containing adenoviral vector genomes.

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  1. Room 1.302 Stopford Building Department of Medicine, Molecular Medicine Unit, University of Manchester School of Medicine, Oxford Road, Manchester, M13 9PT, England

    P R Lowenstein, C E Thomas & M G Castro

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  1. P R Lowenstein
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  2. C E Thomas
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  3. M G Castro
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Lowenstein, P., Thomas, C. & Castro, M. Politically correct gene therapy? A “clean environment” improves gene delivery to the brain!. Gene Ther 6, 463–464 (1999). https://doi.org/10.1038/sj.gt.3300917

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