Lock-equipped six-helix DNA bundle-mediated siSTING delivery ameliorates Alzheimer's disease via cGAS-STING inhibition - PubMed
6 hours ago
- #Alzheimer's disease
- #siRNA delivery
- #DNA nanotechnology
- Alzheimer's disease (AD) progression is linked to microglial inflammation via the cGAS-STING pathway.
- siSTING (small interfering RNA targeting STING) is a therapeutic to silence STING but faces challenges like serum degradation and poor BBB penetration.
- A lock-equipped six-helix DNA bundle was developed for siSTING delivery, protecting it until it reaches AD lesions.
- The DNA bundle releases siSTING in response to high CD64 expression at the lesion site.
- This system suppresses cGAS-STING activation, reduces Aβ plaque deposition, and promotes microglial polarization from M1 to M2.
- The treatment improved memory and learning deficits in AD model mice, offering a novel targeted therapy for AD.