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Injection parameters and virus dependent choice of promoters to improve neuron targeting in the nonhuman primate brain

Gene Therapy volume 21, pages 233–241 (2014)Cite this article

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Abstract

We, like many others, wish to use modern molecular methods to alter neuronal functionality in primates. For us, this requires expression in a large proportion of the targeted cell population. Long generation times make germline modification of limited use. The size and intricate primate brain anatomy poses additional challenges. We surved methods using lentiviruses and serotypes of adeno-associated viruses (AAVs) to introduce active molecular material into cortical and subcortical regions of old-world monkey brains. Slow injections of AAV2 give well-defined expression of neurons in the cortex surrounding the injection site. Somewhat surprisingly we find that in the monkey the use of cytomegalovirus promoter in lentivirus primarily targets glial cells but few neurons. In contrast, with a synapsin promoter fragment the lentivirus expression is neuron specific at high transduction levels in all cortical layers. We also achieve specific targeting of tyrosine hydroxlase (TH)- rich neurons in the locus coeruleus and substantia nigra with a lentvirus carrying a fragment of the TH promoter. Lentiviruses carrying neuron specific promoters are suitable for both cortical and subcortical injections even when injected quickly.

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Acknowledgements

We thank Sebastien Bouret for crucial help with locating and injecting the locus coeruleus, and Rachel Reoli for her kind support with MRI scans. This study was supported by the Intramural Research Program of the National Institute of Mental Health.

DISCLAIMER

The views expressed in this article do not necessarily represent the views of the NIMH, NIH or the United States Government.

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Authors and Affiliations

  1. Laboratory of Neuropsychology, National Institute of Mental Health/NIMH/DHHS, Bethesda, MD, USA

    W Lerchner, B Corgiat, V Der Minassian, R C Saunders & B J Richmond

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  1. W Lerchner
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Correspondence to B J Richmond.

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Lerchner, W., Corgiat, B., Der Minassian, V. et al. Injection parameters and virus dependent choice of promoters to improve neuron targeting in the nonhuman primate brain. Gene Ther 21, 233–241 (2014). https://doi.org/10.1038/gt.2013.75

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