Lipid nanoparticles modeled on cell membranes improve CRISPR gene editing for hemophilia A

The engineered lipid nanoparticles increased in vivo editing efficiency 2.3-fold compared to a benchmark formulation.

• Biomembrane-inspired lipid nanoparticles were developed to enhance liver-targeted delivery of CRISPR-Cas9.
• Transient mRNA delivery via lipid nanoparticles reduced the theoretical risk of insertional mutagenesis associated with viral vectors.
• The treatment achieved efficient and durable gene correction in a hemophilia A mouse model.
• A single dose of lipid nanoparticles restored plasma Factor VIII activity to over 50% of wild-type levels for more than 12 weeks.
• The lipid nanoparticles showed low systemic cytokine induction, undetectable off-target insertions, and no overt toxicity.

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