Evidence map›Paper›PMID 12461167›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2002

Site-directed recombination via bifunctional PNA-DNA conjugates.

Faye A Rogers, Karen M Vasquez, Michael Egholm, Peter M Glazer

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.

0numbers the graph read from it
0cells of the map it votes in
59citing papers in PubMed
2.3field-weighted citation impact, top 12% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

59 citing papers in PubMed, 119 citations in OpenAlex.

  1. Article
  2. Gene editing using gamma modified PNA: HBB gene as a model.Journal, genetic engineering & biotechnology · 2025
    Article
  3. Systemic in utero gene editing as a treatment for cystic fibrosis.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  4. Next generation triplex-forming PNAs for site-specific genome editing of the F508del CFTR mutation.Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society · 2025
    Article
  5. Exploring the DNAHeliyon · 2024
    Article
  6. Review
  7. Article
  8. Article
  9. Review
  10. Review
  11. Peptide nucleic acid-dependent artifact can lead to false-positive triplex gene editing signals.Proceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  12. On the Origins of Homology Directed Repair in Mammalian Cells.International journal of molecular sciences · 2021
    Article
  13. Article
  14. Review
  15. Review
  16. Article
  17. Applications of PNA-laden nanoparticles for hematological disorders.Cellular and molecular life sciences : CMLS · 2019
    Review
  18. Debugging the genetic code: non-viralCurrent opinion in biomedical engineering · 2018
    Article
  19. Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 1 institution in 1 country.

Faye A RogersDepartments of Therapeutic Radiology and Genetics, Yale University School of Medicine, New Haven, CT 06520, USA.
Karen M Vasquez
Michael Egholm
Peter M Glazer
Yale University · US

Funding

TARGETED MUTAGENESIS OF DNA VIA TRIPLE HELIX FORMATIONR01CA064186 · NCI · YALE UNIVERSITY · PI GLAZER, PETER M · 1995 to 2008
$2.6M
RESEARCH TRAINING: RADIATION THERAPY, BIOLOGY, PHYSICST32CA009259 · NCI · YALE UNIVERSITY · PI GLAZER, PETER M · 1985 to 2009
$1.4M
RECOMBINATION INDUCED BY TRIPLEX TARGETED DNA DAMAGER01GM054731 · NIGMS · YALE UNIVERSITY · PI GLAZER, PETER M · 1997 to 2004
$1.4M
NCI NIH HHS CA64186NCI NIH HHS R01 CA064186NCI NIH HHS T32 CA009259NCI NIH HHS T32 CA09259NIGMS NIH HHS GM54731NIGMS NIH HHS R01 GM054731
6 · The paper itself

Abstract

Site-specific DNA binding molecules offer the potential for genetic manipulation of mammalian cells. Peptide nucleic acids (PNAs) are a DNA mimic in which the purine and pyrimidine bases are attached to a polyamide backbone. PNAs bind with high affinity to single-stranded DNA via Watson-Crick base pairing and can form triple helices via Hoogsteen binding to DNAPNA duplexes. Dimeric bis-PNAs capable of both strand invasion and triplex formation can form clamp structures on target DNAs. As a strategy to promote site-directed recombination, a bis-PNA was coupled to a 40-nt donor DNA fragment homologous to an adjacent region in the target gene. The PNA-DNA conjugate was found to mediate site-directed recombination with a plasmid substrate in human cell-free extracts, resulting in correction of a mutation in a reporter gene at a frequency at least 60-fold above background. Induced site-specific recombination was also seen when the bis-PNA and the donor DNA were co-mixed without covalent linkage. In addition, the bis-PNA and the bis-PNA-DNA conjugate were found to induce DNA repair specifically in the target plasmid. Both the PNA-induced recombination and the PNA-induced repair were found to be dependent on the nucleotide excision repair factor, XPA (xeroderma pigmentosum complementation group A protein). These results suggest that the formation of a PNA clamp on duplex DNA creates a helical distortion that strongly provokes DNA repair and thereby sensitizes the target site to recombination. The ability to promote recombination in a site-directed manner using PNA-DNA conjugates may provide a useful strategy to achieve targeted correction of defective genes.

Indexed as

DNA RepairDNADNA-Binding ProteinsHeLa CellsHumansPeptide Nucleic AcidsRecombination, GeneticXeroderma Pigmentosum Group A ProteinDNADNA-Binding ProteinsPeptide Nucleic AcidsXeroderma Pigmentosum Group A ProteinXPA protein, human

Identifiers

PMID12461167
PMCPMC139206
OpenAlexW2006877623

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.