PNA as a Biosupramolecular Tag for Programmable Assemblies and Reactions

Area of Science:

• Biomolecular Engineering and Nanotechnology
• Synthetic Biology
• Nucleic Acid Chemistry

Background:

• Oligonucleotide hybridization enables programmable assemblies with emergent properties.
• DNA nanotechnology has advanced nucleic acid applications, but requires functionalities beyond hybridization.
• Peptide nucleic acids (PNAs) combine DNA hybridization with peptide modularity, offering enhanced stability and functionalization.

Purpose of the Study:

• To explore the utility of peptide nucleic acids (PNAs) as biosupramolecular tags for programming assemblies and reactions.
• To highlight the potential of PNA-functionalized systems for creating complex functional outputs and in vivo applications.
• To demonstrate the compatibility of PNA-based technologies with in vitro evolution for exploring molecular diversity.

Main Methods:

• Utilizing the superior hybridization properties of PNAs, including high stability and sequence fidelity.
• Developing functionalized PNAs for templated reactions to synthesize complex polymers, fluorescent outputs, and bioactive molecules.
• Integrating PNA-modified systems with cellular nucleic acids (mRNA, miRNA) for in live cell applications.
• Employing PNA-tagged macromolecules for creating bioactive assemblies and 3D nanostructures.
• Leveraging DNA-templated synthesis and selection/amplification cycles with PNA-based systems.

Main Results:

• PNAs form highly stable duplexes with DNA/RNA, even with short oligomers, with minimal ionic strength dependence.
• Functionalized PNAs enable robust templated reactions, translating DNA templates into complex functional polymers, fluorescent outputs, and bioactive small molecules.
• PNA-based assemblies and PNA-tagged macromolecules demonstrate in vivo functionality and are suitable for creating bioactive assemblies and nanostructures.
• PNA synthesis tolerance allows encoding small molecules for sequence-based assembly.
• PNA technologies are compatible with iterative selection/amplification, enabling in vitro evolution of synthetic molecules.

Conclusions:

• Peptide nucleic acids (PNAs) represent a versatile platform for advancing DNA nanotechnology and synthetic biology.
• The unique properties of PNAs facilitate the creation of complex, functional molecular assemblies with potential for in vivo applications.
• PNA-based approaches expand the scope and speed of molecular discovery through integration with in vitro evolution techniques.