Bioreducible Gene Delivery Platform that Promotes Intracellular Payload Release and Widespread Brain Dispersion.
Divya RaoGijung KwakHeng WangCharles G EberhartJustin HanesJung Soo SukPublished in: ACS biomaterials science & engineering (2023)
We here introduce a novel bioreducible polymer-based gene delivery platform enabling widespread transgene expression in multiple brain regions with therapeutic relevance following intracranial convection-enhanced delivery. Our bioreducible nanoparticles provide markedly enhanced gene delivery efficacy in vitro and in vivo compared to nonbiodegradable nanoparticles primarily due to the ability to release gene payloads preferentially inside cells. Remarkably, our platform exhibits competitive gene delivery efficacy in a neuron-rich brain region compared to a viral vector under previous and current clinical investigations with demonstrated positive outcomes. Thus, our platform may serve as an attractive alternative for the intracranial gene therapy of neurological disorders.
Keyphrases
- gene therapy
- high throughput
- resting state
- white matter
- cerebral ischemia
- functional connectivity
- induced apoptosis
- sars cov
- optic nerve
- cell cycle arrest
- metabolic syndrome
- gene expression
- multiple sclerosis
- signaling pathway
- adipose tissue
- cell proliferation
- cell death
- long non coding rna
- genome wide identification