Programmable enzymes for targeted gene insertion.

Programmable enzymes, especially CRISPR-associated transposases, now enable kilobase-scale gene insertions, surpassing previous limitations of small-scale editing methods.

• Why it matters: Large-scale gene insertions are crucial for treating genetically heterogeneous disorders with multiple pathogenic variants, but existing methods lacked efficiency and precision for such tasks.
• What they did: The authors review recent advances in discovering and engineering enzymes like recombinases and transposases, utilizing computational mining, directed evolution, and rational design to optimize genome editing tools.
• The result: These developments facilitate precise, large-scale DNA insertions, opening new possibilities for gene therapy and expanding the scope of genome engineering applications.