Prime editing of the β₁ adrenoceptor in the brain restores physiological REM sleep in a mouse model of Alzheimer's disease.

ABSTRACT: Prime editing offers versatile genome modifications with therapeutic potential; yet its use to modulate neural circuitry remains underexplored. Here, we used adeno-associated viral vectors to deliver prime editors into the mouse brain and introduced the naturally occurring Adrb1^A187V variant of the β1-adrenergic receptor, linked to short sleep in humans and mice. Editing reached up to 28.1% in the cortex six months after intracerebroventricular injection and increased excitability of β1-noradrenergic neurons. This enhanced wake-associated behaviors, including home cage activity, locomotion, exploration, and recognition memory, while reducing slow wave activity (SWA) during non-rapid eye movement (NREM) sleep indicating reduced build-up of sleep pressure during active phases. In

SUBMITTER: Bock D 

PROVIDER: S-EPMC12689628 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature