Kim Jin Soo - National University of Singapore

Kim Jin Soo - National University of Singapore

Genome Editing Beyond CRISPR

Abstract:

Genome editing in nuclear, mitochondrial, and chloroplast DNA is broadly useful for biomedical research, medicine, and biotechnology. CRISPR systems, widely used for nuclear DNA editing, are not suitable for organellar DNA editing, due to the difficulty of guide RNA delivery into organelles. Mitochondrial DNA editing paves the way for disease modeling of mitochondrial genetic disorders in cell lines and animals, and can offer treatment options for these diseases with unmet medical needs. Likewise, chloroplast DNA editing in plants provides unique opportunities in plant biotechnology and agriculture, contributing to carbon neutralization. I will present novel tools for A-to-G and C-to-T base editing of organellar DNA in human cells, animals, and plants.

References:

1) Targeted A-to-G base editing in human mitochondrial DNA with programmable deaminases. Cell (2022)
2) Precision mitochondrial DNA editing with high-fidelity DddA-derived base editors. Nat. Biotechnol.(2022)
3) Chloroplast and mitochondrial DNA editing in plants. Nature Plants (2021)
4) Genome-wide target specificity of CRISPR RNA-guided adenine base editors. Nat. Biotechnol. 37, 430 (2019)
5) Correction of a pathogenic gene mutation in human embryos. Nature 548, 413 (2017)
6) Genome-wide target specificities of CRISPR RNA-guided deaminases. Nat. Biotechnol. 35, 475 (2017)
7) Highly efficient RNA-guided base editing in mouse embryos. Nature Biotechnol. 35, 435 (2017)
8) Genome-wide analysis reveals specificities of Cpf1 endonucleases. Nat. Biotechnol. 34, 863 (2016)
9) DNA-free genome editing in plants with CRISPR-Cas9 ribonucleoproteins. Nat. Biotechnol. 33, 1162 (2015)
10) Digenome-seq: Genome-wide profiling of CRISPR-Cas9 off-target effects. Nature Methods 12, 237 (2015)
11) A guide to genome engineering with programmable nucleases. Nat. Rev. Genetics 15, 321 (2014)
12) Targeted genome engineering in human cells with Cas9 RNA-guided endonuclease. Nat. Biotechnol. (2013)