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Efficient gene delivery to the adult and fetal CNS using pseudotyped non-integrating lentiviral vectors

Abstract

Non-integrating lentiviral vectors show considerable promise for gene therapy applications as they persist as long-term episomes in non-dividing cells and diminish risks of insertional mutagenesis. In this study, non-integrating lentiviral vectors were evaluated for their use in the adult and fetal central nervous system of rodents. Vectors differentially pseudotyped with vesicular stomatitis virus, rabies and baculoviral envelope proteins allowed targeting of varied cell populations. Efficient gene delivery to discrete areas of the brain and spinal cord was observed following stereotactic administration. Furthermore, after direct in utero administration (E14), sustained and strong expression was observed 4 months into adulthood. Quantification of transduction and viral copy number was comparable when using non-integrating lentivirus and conventional integrating vector. These data support the use of non-integrating lentiviral vectors as an effective alternative to their integrating counterparts in gene therapy applications, and highlight their potential for treatment of inherited and acquired neurological disorders.

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Acknowledgements

We thank Ruth Seabright, University of Birmingham, for providing the pLP-RVG construct and Paul McCray Jr, University of Iowa, for providing the pHCMVwhvGP64 construct. This work was funded by the Biotechnology and Biological Sciences Research Council. SNW (Philip Gray Memorial Fellow) and SMKB are supported by the Katherine Dormandy Trust and NJW is funded by the Medical Research Council. AJT is supported by The Wellcome Trust.

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Correspondence to A J Thrasher.

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Rahim, A., Wong, A., Howe, S. et al. Efficient gene delivery to the adult and fetal CNS using pseudotyped non-integrating lentiviral vectors. Gene Ther 16, 509–520 (2009). https://doi.org/10.1038/gt.2008.186

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