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Efficient gene transduction of neurons by lentivirus with enhanced neuron-specific promoters

Gene Therapy volume 14, pages 872–882 (2007)Cite this article

Abstract

In the field of basic and clinical neurosciences, it is important to develop a method for easy delivery and persistent expression of transgene in central neurons. We firstly generated lentiviral vectors with five kinds of neuron-specific promoters, such as synapsin I (SYN), calcium/calmodulin-dependent protein kinase II, tubulin alpha I, neuron-specific enolase and platelet-derived growth factor beta chain promoters and then novel hybrid promoters by fusing cytomegalovirus enhancer (E) to those neuron-specific promoters. Neuron-specific expression of green fluorescent protein (GFP) with those promoters was examined in vivo by injecting the lentiviral vectors into the rat neostriatum, thalamus and neocortex. Among all the promoters, SYN promoter displayed the highest specificity for neuronal expression in all the regions examined (more than 96%). Although GFP production by the hybrid promoters was about 2–4 times larger than the non-enhanced promoters, the neuronal specificity was significantly decreased in most cases. However, the neuronal specificity of E/SYN hybrid promoter exhibited the least decrease only in the thalamus. Furthermore, the transcriptional activity and neuronal specificity of E/SYN promoter were sustained for up to 8 weeks. Thus, lentivirus with E/SYN promoter is the best vector for strong persistent expression in neurons.

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Acknowledgements

This research was supported by Grant-in-Aid for Scientific Research 18700341, 16200025, 17650100 and Grant-in-Aid for Scientific Research on Priority Areas System study on higher-order brain functions 17022020 from The Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT).

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Authors and Affiliations

  1. Department of Morphological Brain Science, Graduate School of Medicine, Kyoto University, Kyoto, Japan

    H Hioki, H Kameda, H Nakamura, T Okunomiya, K Ohira, K Nakamura, M Kuroda, T Furuta & T Kaneko

  2. Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency, Kawaguchi, Japan

    K Nakamura & T Kaneko

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  1. H Hioki
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  2. H Kameda
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Correspondence to T Kaneko.

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Supplementary Information accompanies the paper on Gene Therapy website (http://www.nature.com/gt)

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Hioki, H., Kameda, H., Nakamura, H. et al. Efficient gene transduction of neurons by lentivirus with enhanced neuron-specific promoters. Gene Ther 14, 872–882 (2007). https://doi.org/10.1038/sj.gt.3302924

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