Regulated transformation system (RTS): sddi-mediated programmable shut-off and mode switching of base editors - PubMed
5 hours ago
- #Base Editing
- #Gene Regulation
- #Therapeutic Screening
- The study introduces a Regulated Transformation System (RTS) using miniature deaminase inhibitors (Sddis) to control base editing activity.
- Sddis bind specifically to single-stranded DNA deaminases (Sdds), blocking their DNA-binding surfaces to completely inhibit C-to-T editing.
- Engineered ACBE-RTS platform enables switching among four modes (OFF, CBE, ABE, ACBE) with small-molecule inducers like doxycycline and cumate.
- Achieves high editing efficiencies: up to 43.4% C-to-T and 42.9% A-to-G at endogenous human sites.
- Applied in a screening with a 4000-member sgRNA library in MARC-145 cells, identifying key amino acids in monkey CD163 that reduce PRRSV replication.
- Establishes a modular framework for precision therapeutics and genetic research, with potential extension to other base editors like TBE and GBE.