Lipid nanoparticles optimized for large RNA cargo and tissue targeting enhance in vivo genome editing.

Lipid nanoparticle LC-1 achieves up to 79% genome editing efficiency with large 5.7-kb mRNA cargo, outperforming existing formulations across multiple tissues.

• Why it matters: Efficient delivery of large RNA molecules remains a challenge, limiting the potential of lipid nanoparticles for in vivo genome editing and therapeutic applications.
• What they did: A combinatorial library of 384 lipids was screened using a large mRNA reporter to identify lipids optimized for big cargo, leading to the discovery of LC-1 with enhanced delivery properties.
• The result: LC-1's improved interactions and structural stability enable higher editing efficiencies and broader tissue targeting, highlighting cargo size as a crucial factor in lipid nanoparticle design.