Objective:

To develop a genome-editing strategy that minimizes immune response and enhances gene insertion efficiency.

Key Findings:

• INSTALL enables high-fidelity DNA integration across multiple recombinase systems.
• Improved efficiency in human cells and better tolerability in mice compared to traditional dsDNA methods.
• INSTALL-treated animals exhibited minimal inflammation and sustained integration, unlike dsDNA which caused severe immune activation.

Interpretation:

INSTALL represents a significant advancement in genome editing by combining immune-evasive nucleic acids with precise recombinase technology, potentially broadening the applications of gene insertion.

Limitations:

• Further studies are needed to fully understand long-term effects and safety in humans.
• The scalability and practical applications in clinical settings require additional validation.

Conclusion:

INSTALL offers a promising non-viral approach to in vivo genome writing, potentially expanding therapeutic options for gene insertion technologies.