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Publication : Enhancer AAVs for targeting spinal motor neurons and descending motor pathways in rodents and macaque.

First Author  Kussick E Year  2025
Journal  Cell Rep Volume  44
Issue  6 Pages  115730
PubMed ID  40403722 Mgi Jnum  J:392970
Mgi Id  MGI:8216962 Doi  10.1016/j.celrep.2025.115730
Citation  Kussick E, et al. (2025) Enhancer AAVs for targeting spinal motor neurons and descending motor pathways in rodents and macaque. Cell Rep 44(6):115730
abstractText  Experimental access to cell types within the mammalian spinal cord is severely limited by the availability of genetic tools. To enable access to spinal motor neurons (SMNs) and SMN subtypes, we generated single-cell multiome datasets from mouse and macaque spinal cords and discovered putative enhancers for each neuronal population. We cloned these enhancers into adeno-associated viral vectors driving a reporter fluorophore and functionally screened them in the mouse. We extensively characterized the most promising candidate enhancers in rat and macaque and developed an optimized pan-SMN enhancer virus. Additionally, we generated derivative viruses expressing iCre297T recombinase or ChR2-EYFP for labeling and functional studies, and we created a single vector with combined enhancer elements to achieve simultaneous labeling of layer 5 extratelencephalic projecting neurons and SMNs. This unprecedented SMN toolkit will enable future investigations of cell type function across species and potential therapeutic interventions for human neurodegenerative diseases.
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