| First Author | Mich JK | Year | 2021 |
| Journal | Cell Rep | Volume | 34 |
| Issue | 13 | Pages | 108754 |
| PubMed ID | 33789096 | Mgi Jnum | J:341583 |
| Mgi Id | MGI:6706254 | Doi | 10.1016/j.celrep.2021.108754 |
| Citation | Mich JK, et al. (2021) Functional enhancer elements drive subclass-selective expression from mouse to primate neocortex. Cell Rep 34(13):108754 |
| abstractText | Viral genetic tools that target specific brain cell types could transform basic neuroscience and targeted gene therapy. Here, we use comparative open chromatin analysis to identify thousands of human-neocortical-subclass-specific putative enhancers from across the genome to control gene expression in adeno-associated virus (AAV) vectors. The cellular specificity of reporter expression from enhancer-AAVs is established by molecular profiling after systemic AAV delivery in mouse. Over 30% of enhancer-AAVs produce specific expression in the targeted subclass, including both excitatory and inhibitory subclasses. We present a collection of Parvalbumin (PVALB) enhancer-AAVs that show highly enriched expression not only in cortical PVALB cells but also in some subcortical PVALB populations. Five vectors maintain PVALB-enriched expression in primate neocortex. These results demonstrate how genome-wide open chromatin data mining and cross-species AAV validation can be used to create the next generation of non-species-restricted viral genetic tools. |
