Significant downregulation of Alzheimer's amyloid-β levels enabled by engineered DNA nanomaterials
Year: 2024
Type: article
Abstract: Although there are no effective therapies to block or reverse Alzheimer's disease (AD) progression at present, a promising therapeutic strategy is to reduce levels of amyloid-β (Aβ) proteins, which drive the formation of amyloid plaque, a primary hallmark in AD brains. Herein, we report that amphiphilic lipid-DNA molecules (LD) were designed by incorporating a long alkyl chain into the nucleotide base. It significantly down-regulated Alzheimer's Aβ levels in vivo and in vitro. In contrast to small-molecule chemical drugs and antibody therapies, the assembled DNA nanoparticles allowed them to effectively cross the blood-brain barrier (BBB) and accumulate in the brain, increasing the therapeutic effects. Notably, lipid-DNA downregulated the levels of Aβ peptides significantly in vitro. AD mice model experiments demonstrated that the LD-treated groups exhibited a rapid cognition behavioral improvement, which was associated with brain engagement of LD and reduced Aβ levels. Thus, the molecularly engineered DNA nanomaterials effectively regulated Aβ peptides. This work might provide a promising DNA engineering strategy for AD treatment.
Source: Fundamental Research
Institutions: Tsinghua University, East China Normal University, Harvard University, Chinese Academy of Sciences, Massachusetts General Hospital, Changchun Institute of Applied Chemistry, State Key Laboratory of Rare Earth Resources Utilization, DWI – Leibniz Institute for Interactive Materials, RWTH Aachen University
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W4393281944