Elucidating the Principles of Gene Editing Inhibitors / Professor Nam Ki-hyun (College of Liberal Arts)
- 24.03.08 / 박서연
Professor Nam ki-hyun of the College of Liberal Arts, in collaboration with Prof. Ailong Ke of Cornell University (USA), Prof. Chunyi Hu of the National University of Singapore (Singapore), and Prof. Yan Zhang of the University of Michigan (USA), has revealed the principles of type I CRISPR-mediated genome editing and transcriptional repression in human cells (Title: Exploiting activation and inactivation mechanisms in type I-C CRISPR-Cas3 for genome-editing applications). Molecular Cell (Impact Factor 16), a sister journal of the life sciences journal Cell, where the study was reported, is a prestigious journal ranked in the top 2.6% of biochemistry journals.
CRISPR, better known as genetic scissors, is a field of research that won the 2020 Nobel Prize in Chemistry and has recently led to the development of therapies for incurable diseases. The Type I CRISPR-Cas system utilizes an RNA-guided cascade complex to identify a matching DNA target and the nuclease-helicase Cas3 to degrade it. Types I-C are known as favorable targets for human gene editing because they are small in size and highly active in generating large-scale genome deletions in human cells. In this study, four cryo-electron microscopy structures were used to reveal the mechanism of RNA-induced DNA binding and cleavage at high resolution. Structural analysis revealed that AcrIC8 inhibits PAM recognition through allosteric inhibition, while AcrIC9 achieves this through direct competition. The study confirmed that both inhibitors potently inhibit I-C-mediated genome editing and transcriptional modulation in human cells
These results provide insight into the first off-switch for Type I CRISPR eukaryotic genome engineering and are expected to have applications in the future development of CRISPR-based gene-editing therapies.
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This content is translated from Korean to English using the AI translation service DeepL and may contain translation errors such as jargon/pronouns.
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Elucidating the Principles of Gene Editing Inhibitors / Professor Nam Ki-hyun (College of Liberal Arts) |
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2024-03-08
7965
Professor Nam ki-hyun of the College of Liberal Arts, in collaboration with Prof. Ailong Ke of Cornell University (USA), Prof. Chunyi Hu of the National University of Singapore (Singapore), and Prof. Yan Zhang of the University of Michigan (USA), has revealed the principles of type I CRISPR-mediated genome editing and transcriptional repression in human cells (Title: Exploiting activation and inactivation mechanisms in type I-C CRISPR-Cas3 for genome-editing applications). Molecular Cell (Impact Factor 16), a sister journal of the life sciences journal Cell, where the study was reported, is a prestigious journal ranked in the top 2.6% of biochemistry journals.
CRISPR, better known as genetic scissors, is a field of research that won the 2020 Nobel Prize in Chemistry and has recently led to the development of therapies for incurable diseases. The Type I CRISPR-Cas system utilizes an RNA-guided cascade complex to identify a matching DNA target and the nuclease-helicase Cas3 to degrade it. Types I-C are known as favorable targets for human gene editing because they are small in size and highly active in generating large-scale genome deletions in human cells. In this study, four cryo-electron microscopy structures were used to reveal the mechanism of RNA-induced DNA binding and cleavage at high resolution. Structural analysis revealed that AcrIC8 inhibits PAM recognition through allosteric inhibition, while AcrIC9 achieves this through direct competition. The study confirmed that both inhibitors potently inhibit I-C-mediated genome editing and transcriptional modulation in human cells
These results provide insight into the first off-switch for Type I CRISPR eukaryotic genome engineering and are expected to have applications in the future development of CRISPR-based gene-editing therapies.
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