'Caged' peptide nucleic acids activated by red light in a singlet oxygen mediated process

Area of Science:

• Chemical Biology
• Molecular Biology
• Biotechnology

Background:

• Current caged nucleic acid binders use high-energy light (<450 nm), which damages cells.
• Cellular absorption of shorter wavelengths limits their application.
• A shift to visible light (>550 nm) is desirable for safer and more effective gene control.

Purpose of the Study:

• To develop a novel caged peptide nucleic acid (PNA) system.
• To enable temporal and spatial control of gene expression using visible light.
• To overcome the limitations of UV-activated caged nucleic acid binders.

Main Methods:

• Synthesized a cyclic peptide nucleic acid (PNA) with a 9,10-dialkoxy-substituted anthracene linker.
• Designed the PNA sequence to be complementary to microRNA-92 (miR-92).
• Utilized red light (635 nm) and pyropheophorbide-a to induce uncaging via singlet oxygen.

Main Results:

• The cyclic PNA remained 'caged' and did not bind to complementary nucleic acids.
• Red light exposure in the presence of pyropheophorbide-a triggered PNA uncaging.
• Singlet oxygen cleaved the anthracene linker, forming a linear PNA that efficiently binds RNA.

Conclusions:

• This study presents the first red light-activated caged peptide nucleic acid.
• The developed system offers a safer alternative to UV-activated systems for gene regulation.
• This advancement holds potential for precise spatiotemporal control in biological systems.