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Functional enhancer elements drive subclass-selective expression from mouse to primate neocortex

ABSTRACT: Functional enhancer elements drive subclass-selective expression from mouse to primate neocortex

PROVIDER: PRJNA988149 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR25041800_1.fastq.gz	Fastqsanger.gz
	SRR25041800_2.fastq.gz	Fastqsanger.gz
	SRR25041900_1.fastq.gz	Fastqsanger.gz
	SRR25041900_2.fastq.gz	Fastqsanger.gz
	SRR25042000_1.fastq.gz	Fastqsanger.gz

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Functional enhancer elements drive subclass-selective expression from mouse to primate neocortex

Project description:Viral genetictools that target specificbraincell types could transform basicneuroscienceand targeted gene therapy. Here, we use comparative open chromatin analysis to identify thousands of human-neocortical-subclass-specific putative enhancers from across the genome tocontrol gene expressionin 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 ofParvalbumin(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 primateneocortex. 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.

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