Optochemical control of deoxyoligonucleotide function via a nucleobase-caging approach

Area of Science:

• Synthetic biology
• Molecular biology
• Biochemistry

Background:

• Synthetic oligonucleotides are versatile tools for modulating biological processes like gene expression and DNA repair.
• Current limitations in spatial and temporal control hinder the precise investigation of complex biological mechanisms.
• Light offers a highly controllable external stimulus for precise regulation of biological functions.

Purpose of the Study:

• To develop and showcase methods for optochemical regulation of oligonucleotide activity using light.
• To enable precise spatial and temporal control over DNA and gene expression using light-activated oligonucleotides.
• To explore the potential of light-activated DNA for advanced applications such as logic operations and calculations.

Main Methods:

• Utilizing photolabile caging groups on oligonucleotides to create light-switchable nucleic acid functions.
• Designing and synthesizing caged nucleobases for photoregulation of DNA.
• Applying caged triplex-forming oligomers and DNA decoys for transcriptional control.
• Developing light-activated antisense agents for translational control.

Main Results:

• Achieved optochemical activation and deactivation of gene expression at both transcriptional and translational levels.
• Demonstrated spatial and temporal control over DNA functions using light-induced uncaging.
• Explored light-triggered DNA enzymatic activity, amplification, and mutagenesis.
• Developed light-activated DNA logic operations for potential complex computations.

Conclusions:

• Optochemical regulation via caged nucleobases provides precise spatial and temporal control over oligonucleotide function.
• This approach significantly enhances the utility of synthetic oligonucleotides as research tools in molecular and cell biology.
• Light-activated DNA technologies hold promise for future applications in synthetic biology and DNA-based computing.