Rett syndrome, primarily affecting girls, is caused by mutations in the MECP2 gene. While CRISPR-Cas9 offers hope for correcting such genetic mutations, delivering its components efficiently into cells has been a significant challenge in developing effective gene therapies.
To address this, Prof. Lee's team combined nanotechnology with CRISPR-Cas9, creating the Magnetic Nanoparticle-Assisted Genome Editing (MAGE) system. MAGE uses specially designed magnetic nanoparticles to deliver CRISPR components more effectively into cells.
The system consists of magnetic core-shell nanoparticles with a zinc-doped iron oxide core coated with mesoporous silica and polyethylenimine layers. This design allows the nanoparticles to carry and protect multiple CRISPR plasmids. MAGE employs magnetofection to improve cellular uptake and magnetic-activated cell sorting to increase the proportion of edited cells. Applying MAGE to neural progenitor cells derived from a Rett syndrome patient, the team achieved remarkable results: (i) 99.3% plasmid delivery efficiency, (ii) 42.95% gene repair efficiency, and (iii) restored MECP2 protein expression and improved neuronal function in edited cells
"Our MAGE-CRISPR system represents a significant leap forward in gene therapy," says Prof. Lee. "By combining CRISPR with magnetic nanoparticles, we've created a powerful tool that could potentially transform the treatment of other genetic disorders, like Rett syndrome."
This non-viral approach enhances efficiency and safety compared to viral delivery methods, reducing the risk of unwanted genomic insertions and immune responses. The team plans to validate this technology further in more complex models, potentially leading to clinical trials. The versatility of MAGE-CRISPR suggests its potential application in treating various genetic disorders beyond Rett syndrome.
This groundbreaking research opens new avenues in gene therapy, offering hope to patients affected by genetic disorders and bringing us closer to effective treatments for previously incurable genetic conditions and diseases.
PUBLICATION: This work was recently published in Advanced Science, “Magnetic Nanoparticle-Assisted Non-Viral CRISPR-Cas9 for Enhanced Genome Editing to Treat Rett Syndrome”, 2024, https://doi.org/10.1002/advs.202306432
CORRESPONDENCE: Prof. Ki-Bum Lee (Rutgers University), https://kblee.rutgers.edu/
