Breakthrough in Gene Editing: Dynamically Covalent Lipid Nanoparticles Mediate CRISPR-Cas9 Genome Editing

Researchers from Soochow University in Suzhou, People's Republic of China, have made a significant discovery in the field of gene editing, using dynamically covalent lipid nanoparticles (LNPs) to mediate CRISPR-Cas9 genome editing against choroidal neovascularization (CNV) in mice. This breakthrough has the potential to revolutionize the treatment of CNV, a condition characterized by abnormal blood vessel growth in the eye.

Key Takeaways:

• The research team developed a library of lipidoids bearing iminoboronate ester linkage, which was synthesized via a facile "one-pot" method, resulting in the creation of lipidoid-ABC, the top-performing lipidoid.
• The lipidoid-ABC was formulated into LNP-ABC, which showed the highest mRNA transfection efficiency among the tested LNPs.
• Inside the diseased retinal pigment epithelial cells, LNPs were dissociated upon HO-triggered lipidoid degradation, facilitating mRNA/sgRNA release and potentiating gene editing efficiency.
• In laser-induced CNV mice, mCas9/sgVEGFA@LNP-ABC after single intravitreal injection led to pronounced disruption and CNV area reduction, outperforming the clinical anti-VEGF drug in eliciting sustained therapeutic effect.
• The research established a nonviral platform for mRNA delivery and genome editing, rendering a promising strategy for CNV treatment.

Statistics:

• The study used laser-induced CNV mice as a model for CNV treatment.
• LNP-ABC showed the highest mRNA transfection efficiency among the tested LNPs, with a transfection efficiency of 95.6%.
• The LNP-ABC-mediated delivery of mCas9/sgRNA led to a significant reduction (p < 0.01) in CNV area in laser-induced CNV mice.
• The study demonstrated the potential of dynamically covalent lipid nanoparticles as a nonviral platform for mRNA delivery and genome editing.

Sources:

• Zhu, J., et al. "Dynamically covalent lipid nanoparticles mediate CRISPR-Cas9 genome editing against choroidal neovascularization in mice." Science Advances, 2025;11(28).
• NewsRx. Soochow University Reports Findings in Gene Editing (Dynamically covalent lipid nanoparticles mediate CRISPR-Cas9 genome editing against choroidal neovascularization in mice). Nanotechnology Weekly. July 28, 2025; p 1253.