PNA as a Biosupramolecular Tag for Programmable Assemblies and Reactions
Open accessAbstract
The programmability of oligonucleotide hybridization offers an attractive platform for the design of assemblies with emergent properties or functions. Developments in DNA nanotechnologies have transformed our thinking about the applications of nucleic acids. Progress from designed assemblies to functional outputs will continue to benefit from functionalities added to the nucleic acids that can participate in reactions or interactions beyond hybridization. In that respect, peptide nucleic acids (PNAs) are interesting because they combine the hybridization properties of DNA with the modularity of peptides. In fact, PNAs form more stable duplexes with DNA or RNA than the corresponding natural homoduplexes. The high stability achieved with shorter oligomers (an 8-mer is sufficient for a stable duplex at room temperature) typically results in very high sequence fidelity in the hybridization with negligible impact of the ionic strength of the buffer due to the lack of electrostatic repulsion between the duplex strands. The simple peptidic backbone of PNA has been shown to be tolerant of modifications with substitutions that further enhance the duplex stability while providing opportunities for functionalization. Moreover, the metabolic stability of PNAs facilitates their integration into systems that interface with biology. Over the past decade, there has been a growing interest in using PNAs as biosupramolecular tags to program assemblies and reactions. A series of robust templated reactions have been developed with functionalized PNA. These reactions can be used to translate DNA templates into functional polymers of unprecedented complexity, fluorescent outputs, or bioactive small molecules. Furthermore, cellular nucleic acids (mRNA or miRNA) have been harnessed to promote assemblies and reactions in live cells. The tolerance of PNA synthesis also lends itself to the encoding of small molecules that can be further assembled on the basis of their nucleic acid sequences. It is now well-established that hybridization-based assemblies displaying two or more ligands can interact synergistically with a target biomolecule. These assemblies have now been shown to be functional in vivo. Similarly, PNA-tagged macromolecules have been used to prepare bioactive assemblies and three-dimensional nanostructures. Several technologies based on DNA-templated synthesis of sequence-defined polymers or DNA-templated display of ligands have been shown to be compatible with reiterative cycles of selection/amplification starting with large libraries of DNA templates, bringing the power of in vitro evolution to synthetic molecules and offering the possibility of exploring uncharted molecular diversity space with unprecedented scope and speed.
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PNA:DNA duplex has high stability.
“We opted for PNA based on the high stability of the PNA:DNA duplex and the simplicity of its chemistry (Figure 1, this work).32−34”
From Sequencing of <scp>d</scp>/<scp>l</scp>-DNA and XNA by Templated-Synthesis (2025) · cites this paper as [34]
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Self-citation
- Authors
- Barluenga, S., & Winssinger, N.
- Affiliations
- Department of Organic Chemistry, NCCR Chemical Biology, University of Geneva, 30 quai Ernest Ansermet, Geneva, Switzerland
- University of Geneva (CH)
- Corresponding author
- Winssinger, Nicolas
- ORCID
- Winssinger, Nicolas
- Venue
- Accounts of Chemical Research
- Publisher
- American Chemical Society (ACS)
- Published
- 2015-05-07
- Volume
- 48
- Issue
- 5
- Pages
- 1319-1331
- ISSN
- 0001-4842 (ISSN-L)
- 1520-4898
- OpenAlex
- W1561759065
- Cited by
- 77
- References
- 96
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 6 · 2023: 4 · 2022: 9 · 2021: 8 · 2020: 9 · 2019: 7 · 2018: 7 · 2017: 10 · 2016: 6 · 2015: 6
- FWCI
- 4.20
- Type
- journal article
- Language
- en
- Open access
- Licence
- cc-by
- Locations
- Accounts of Chemical Research (publishedVersion)
- PubMed (publishedVersion)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- Funders
- European Research Council
- Human Frontier Science Program
- Agence Nationale de la Recherche
- Schweizerische Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Advanced biosensing and bioanalysis techniques
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Biological Computing
- Keywords
- peptide nucleic acid, DNA-templated synthesis, oligonucleotide hybridization, DNA nanotechnology, in vitro evolution, sequence-defined polymers, bioactive small molecules, nanostructures, programmable assembly
- MeSH terms
- DNA, HeLa Cells, Humans, Models, Molecular, Molecular Structure, Peptide Nucleic Acids, Nanostructures, MCF-7 Cells
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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