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A CRISPR-Cas9-Based Near-Infrared Upconversion-Activated DNA Methylation Editing System
Jiadong Chi1, Jingzhu Zhao1, Songfeng Wei1
1Department of Thyroid and Neck Tumor, Tianjin Medical University Cancer Institute and Hospital, Oncology Key Laboratory of Cancer Prevention and Therapy, National Clinical, Research Center of Cancer, 300060Tianjin, China.
ACS Applied Materials & Interfaces
|February 2, 2021
Summary
Researchers developed a novel DNA methylation editing system (CNAMS) using CRISPR-Cas9 technology. This system allows for precise, light-activated control over DNA methylation, offering new possibilities for epigenetic research and disease treatment.
Area of Science:
- Epigenetics and Molecular Biology
- Gene Regulation
- Biotechnology
Background:
- DNA methylation is a critical epigenetic marker influencing gene expression, cellular function, and phenotype.
- Targeted manipulation of DNA methylation for specific genes presents significant challenges in research and therapeutics.
Purpose of the Study:
- To design and validate a novel system for optogenetic editing of DNA methylation.
- To enable spatiotemporal control over DNA methylation status using light-activated components.
- To extend the spectral sensitivity of DNA methylation editing to near-infrared (NIR) light for remote manipulation.
Main Methods:
- Engineered fusion proteins incorporating photosensitive CRY2PHR, DNMT3A/TET1 catalytic domains, CIBN, and catalytically inactive Cas9 (dCas9).
- Developed a clustered regularly interspaced palindromic repeats-Cas9-based near-infrared upconversion-activated DNA methylation editing system (CNAMS).
- Integrated upconversion nanoparticles to enable NIR light activation of the CNAMS system.
Main Results:
- The CNAMS system demonstrated controlled DNA methylation editing in response to blue light, achieving spatiotemporal precision.
- Incorporation of upconversion nanoparticles successfully extended the system's spectral sensitivity to NIR light.
- The developed system facilitates remote DNA methylation editing, a significant advancement in the field.
Conclusions:
- The CNAMS system represents a significant advancement for specific DNA methylation editing.
- This technology offers broad utility for functional studies in epigenetic regulation.
- The CNAMS system holds potential for developing therapeutic strategies for epigenetic-related diseases.
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