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Prime Editing in Dividing and Quiescent Cells
Irina O Petrova1, Svetlana A Smirnikhina1
1Laboratory of Genome Editing, Research Center for Medical Genetics, Moskvorechye 1, 115478 Moscow, Russia.
International Journal of Molecular Sciences
|May 7, 2025
Summary
Prime editing, a genome editing tool, is more efficient in dividing cells due to higher dNTPs and repair enzymes. Inhibiting SAMHD1 boosts prime editing efficiency by increasing dNTPs.
Area of Science:
- Molecular Biology
- Genetics
- Biotechnology
Background:
- Prime editing is a versatile genome editing technology utilizing reverse transcription.
- Its efficiency is notably higher in dividing cells, a phenomenon not fully explained by its non-homologous repair mechanism.
Purpose of the Study:
- To elucidate the mechanistic basis for enhanced prime editing in dividing cells.
- To identify strategies for improving prime editing efficiency.
Main Methods:
- Review of existing literature on prime editing mechanisms and cellular processes.
- Analysis of the roles of dNTP levels, DNA repair pathways (FEN1, LIG1, MMR), and antiviral defenses (SAMHD1) in prime editing.
Main Results:
- Dividing cells offer a favorable environment for prime editing, characterized by abundant dNTPs and active DNA repair machinery (FEN1, LIG1).
- DNA mismatch repair pathways counteract prime editing, while SAMHD1 restricts dNTP availability in non-dividing cells.
- Mitigating SAMHD1 activity significantly enhances prime editing efficiency.
Conclusions:
- The enhanced efficiency of prime editing in dividing cells is attributed to cellular metabolic and repair factors.
- Targeting SAMHD1 presents a promising strategy to overcome limitations and improve prime editing efficacy, particularly in non-dividing cells.
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