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Publication : Considerations related to the use of short neuropeptide promoters in viral vectors targeting hypothalamic neurons.

First Author  Kakava-Georgiadou N Year  2019
Journal  Sci Rep Volume  9
Issue  1 Pages  11146
PubMed ID  31366942 Mgi Jnum  J:286131
Mgi Id  MGI:6387439 Doi  10.1038/s41598-019-47417-9
Citation  Kakava-Georgiadou N, et al. (2019) Considerations related to the use of short neuropeptide promoters in viral vectors targeting hypothalamic neurons. Sci Rep 9(1):11146
abstractText  Targeting specific neuronal cell types is a major challenge for unraveling their function and utilizing specific cells for gene therapy strategies. Viral vector tools are widely used to target specific cells or circuits for these purposes. Here, we use viral vectors with short promoters of neuropeptide genes to target distinct neuronal populations in the hypothalamus of rats and mice. We show that lowering the amount of genomic copies is effective in increasing specificity of a melanin-concentrating hormone promoter. However, since too low titers reduce transduction efficacy, there is an optimal titer for achieving high specificity and sufficient efficacy. Other previously identified neuropeptide promoters as those for oxytocin and orexin require further sequence optimization to increase target specificity. We conclude that promoter-driven viral vectors should be used with caution in order to target cells specifically.
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