| Autor: |
Nagy, M. Aurel, Price, Spencer, Wang, Kristina, Gill, Stanley, Ren, Erika, Jayne, Lorna, Pajak, Victoria, Deighan, Sarah, Bin Liu, Xiaodong Lu, Diallo, Aissatou, Shih-Ching Lo, Kleiman, Robin, Henderson, Christopher, Junghae Suh, Griffith, Eric C., Greenberg, Michael E., Hrvatin, Sinisa |
| Předmět: |
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| Zdroj: |
Proceedings of the National Academy of Sciences of the United States of America; 12/3/2024, Vol. 121 Issue 49, p1-16, 33p |
| Abstrakt: |
Spinal motor neuron (MN) dysfunction is the cause of a number of clinically significant movement disorders. Despite the recent approval of gene therapeutics targeting these MN-related disorders, there are no viral delivery mechanisms that achieve MN-restricted transgene expression. In this study, chromatin accessibility profiling of genetically defined mouse MNs was used to identify candidate cis-regulatory elements (CREs) capable of driving MN-selective gene expression. Subsequent testing of these candidates identified two CREs that confer MN-selective gene expression in the spinal cord as well as reduced off-target expression in dorsal root ganglia. Within one of these candidate elements, we identified a compact core transcription factor (TF)-binding region that drives MN-selective gene expression. Finally, we demonstrated that selective spinal cord expression driven by this mouse CRE is preserved in non-human primates. These findings suggest that cell-type-selective viral reagents in which cell-type-selective CREs drive restricted gene expression will be valuable research tools in mice and other mammalian species, with potentially significant therapeutic value in humans. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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