Evidence map›Paper›PMID 35235944›Full record

ArticleNucleic acids research2022

Antispacer peptide nucleic acids for sequence-specific CRISPR-Cas9 modulation.

Nicholas G Economos, Elias Quijano, Kelly E W Carufe, J Dinithi R Perera, Peter M Glazer

Abstract read
In one paragraph

Article in Nucleic acids research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
–field-weighted citation impact
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

10 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. CRISPR/Cas9 Landscape: Current State and Future Perspectives.International journal of molecular sciences · 2023
    Review
  7. Article
  8. Article
  9. Article
  10. 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

5 authors.

Nicholas G EconomosDepartment of Therapeutic Radiology, Yale School of Medicine, New Haven, CT 06520 USA.ORCID 0000-0003-4691-808X
Elias QuijanoDepartment of Therapeutic Radiology, Yale School of Medicine, New Haven, CT 06520 USA.ORCID 0000-0001-9747-4007
Kelly E W CarufeDepartment of Therapeutic Radiology, Yale School of Medicine, New Haven, CT 06520 USA.
J Dinithi R PereraDepartment of Therapeutic Radiology, Yale School of Medicine, New Haven, CT 06520 USA.
Peter M GlazerDepartment of Therapeutic Radiology, Yale School of Medicine, New Haven, CT 06520 USA.

Funding

MEDICAL SCIENTIST TRAINING PROGRAMT32GM007205 · NIGMS · YALE UNIVERSITY · PI KAZMIERCZAK, BARBARA I · 1985 to 2019
$42.9M
Targeting DNA Repair for Cancer Therapy.R35CA197574 · NCI · YALE UNIVERSITY · PI PETER M GLAZER · 2017 to 2026
$8.6M
Nonenzymatic Gene Editing in Treatment of Heredity SpherocytosisR01HL139756 · NHLBI · YALE UNIVERSITY · PI GALLAGHER, PATRICK G, GLAZER, PETER M · 2019 to 2022
$2.4M
PNA Nanoparticles for Gene Editing In VivoU01AI145965 · NIAID · YALE UNIVERSITY · PI GLAZER, PETER M, LY, DANITH H · 2019 to 2022
$1.6M
Mechanisms of PNA-mediated gene therapy for hematologic diseaseF30HL149185 · NHLBI · YALE UNIVERSITY · PI ECONOMOS, NICHOLAS GEORGE · 2019 to 2020
$60k
NCI NIH HHS R35 CA197574NHLBI NIH HHS F30 HL149185NHLBI NIH HHS R01 HL139756NIAID NIH HHS U01 AI145965NIGMS NIH HHS T32 GM007205
6 · The paper itself

Abstract

Despite the rapid and broad implementation of CRISPR-Cas9-based technologies, convenient tools to modulate dose, timing, and precision remain limited. Building on methods using synthetic peptide nucleic acids (PNAs) to bind RNA with unusually high affinity, we describe guide RNA (gRNA) spacer-targeted, or 'antispacer', PNAs as a tool to modulate Cas9 binding and activity in cells in a sequence-specific manner. We demonstrate that PNAs rapidly and efficiently target complexed gRNA spacer sequences at low doses and without design restriction for sequence-selective Cas9 inhibition. We further show that short PAM-proximal antispacer PNAs achieve potent cleavage inhibition (over 2000-fold reduction) and that PAM-distal PNAs modify gRNA affinity to promote on-target specificity. Finally, we apply antispacer PNAs for temporal regulation of two dCas9-fusion systems. These results present a novel rational approach to nucleoprotein engineering and describe a rapidly implementable antisense platform for CRISPR-Cas9 modulation to improve spatiotemporal versatility and safety across applications.

Indexed as

Peptide Nucleic AcidsRNA, Guide, CRISPR-Cas SystemsCRISPR-Cas SystemsGene EditingPeptide Nucleic AcidsRNA, Guide, CRISPR-Cas Systems

Identifiers

PMID35235944
PMCPMC9177974

What OpenQuestion holds

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LicenceCC BY-NC
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.