ArticleProceedings of the National Academy of Sciences of the United States of America2021
Peptide nucleic acid-dependent artifact can lead to false-positive triplex gene editing signals.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
5 citing papers in PubMed, 11 citations in OpenAlex.
- Shorter Peptide Nucleic Acid Probes Improve Affibody-Mediated Peptide Nucleic Acid-Based Pretargeting.ACS pharmacology & translational science · 2024Article
- CRISPR/Cas9 Landscape: Current State and Future Perspectives.International journal of molecular sciences · 2023Review
- Programmable site-specific DNA double-strand breaks via PNA-assisted prokaryotic Argonautes.Nucleic acids research · 2023Article
- Recent Advances in Improving Gene-Editing Specificity through CRISPR-Cas9 Nuclease Engineering.Cells · 2022Review
- Perspectives on conformationally constrained peptide nucleic acid (PNA): insights into the structural design, properties and applications.RSC chemical biology · 2022Review
Corrections and comments
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Authors and funding
19 authors at 1 institution in 1 country.
Funding
Abstract
Triplex gene editing relies on binding a stable peptide nucleic acid (PNA) sequence to a chromosomal target, which alters the helical structure of DNA to stimulate site-specific recombination with a single-strand DNA (ssDNA) donor template and elicits gene correction. Here, we assessed whether the codelivery of PNA and donor template encapsulated in Poly Lactic-co-Glycolic Acid (PLGA)-based nanoparticles can correct sickle cell disease and x-linked severe combined immunodeficiency. However, through this process we have identified a false-positive PCR artifact due to the intrinsic capability of PNAs to aggregate with ssDNA donor templates. Here, we show that the combination of PNA and donor templates but not either agent alone results in different degrees of aggregation that result in varying but highly reproducible levels of false-positive signal. We have identified this phenomenon in vitro and confirmed that the PNA sequences producing the highest supposed correction in vitro are not active in vivo in both disease models, which highlights the importance of interrogating and eliminating carryover of ssDNA donor templates in assessing various gene editing technologies such as PNA-mediated gene editing.
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Registered trials
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