Improving twin prime editing tools for gene editing and treatment of spinocerebellar ataxia type 3

A 1.75 ± 0.21-fold increase in gene editing efficiency was achieved using an optimized twin prime editing platform.

• Twin prime editing combines two coordinated prime editor complexes for extensive genomic modifications.
• Enhancements to editing efficiency and precision were realized by engineering components of conventional prime editing systems.
• The La-domain-fused prime editor and optimized prime editing guide RNAs contributed to improved outcomes without increasing unintended edits.
• Efficient knock-in of a ~2.8 kb GFP transgene was accomplished at target loci.
• The method successfully removed an expanded polyQ tract in an engineered cell line modeling spinocerebellar ataxia type 3.

Simplified