Base editing of organellar DNA with programmable deaminases
Jin-Soo Kim1,2, Jia Chen3,4
1NUS Synthetic Biology for Clinical & Technological Innovation (SynCTI) and Department of Biochemistry, National University of Singapore, Singapore, Singapore. jskim01@snu.ac.kr.
Nature Reviews. Molecular Cell Biology
|October 4, 2023
Summary
New CRISPR-free base editors enable precise editing of organellar DNA in mitochondria and chloroplasts. These tools offer potential for studying genetic disorders, ageing, and developing novel therapeutics and agricultural applications.
Area of Science:
- Molecular Biology
- Genetics
- Biotechnology
Background:
- Mitochondria and chloroplasts possess their own genomes, crucial for cellular functions like energy production and carbon fixation.
- Mutations in organellar DNA are implicated in genetic disorders, aging, and diseases such as cancer.
- Efficient tools for targeted organellar DNA editing are lacking, hindering research and therapeutic development.
Purpose of the Study:
- To review recent advancements in CRISPR-free base editors for organellar DNA editing.
- To discuss the application of these editors in mitochondrial and plastid genomes.
- To identify limitations and propose future improvements for these editing technologies.
Main Methods:
- Development of CRISPR-free, protein-only base editors, including cytosine base editors (DdCBEs) and adenine base editors (ABEs).
- Application of these editors for targeted DNA editing in vitro, human cell lines, animals, and plants.
- In vitro characterization of programmable deaminases for organellar DNA manipulation.
Main Results:
- Demonstration of targeted organellar DNA editing using novel base editors in various biological systems.
- Successful application of base editors for mitochondrial DNA editing in animals and plastid genome editing in plants.
- Identification of current precision and efficiency limitations of these base editing tools.
Conclusions:
- CRISPR-free base editors represent a significant advancement for organellar DNA editing.
- These tools hold promise for fundamental research, therapeutic interventions, and agricultural improvements.
- Further optimization is needed to enhance the precision and efficiency of organellar base editing for broader applications.
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