ArticleNature communications2022
Guide RNAs containing universal bases enable Cas9/Cas12a recognition of polymorphic sequences.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 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.
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.
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Who cites it
20 citing papers in PubMed, 46 citations in OpenAlex.
- crRNA Truncation MinimizesJACS Au · 2026Article
- Environmental DNA-based RPA-CRISPR/Cas12a assay for on-site detection of chironomid larvae in aquatic environments.Pest management science · 2026Article
- Review
- HPV-driven cancers: a looming threat and the potential of CRISPR/Cas9 for targeted therapy.Virology journal · 2025Review
- Linking CRISPR-Cas9 double-strand break profiles to gene editing precision with BreakTag.Nature biotechnology · 2025Article
- A naked-eye biosensing system based on one-pot RPA-CRISPR/Cas12a driver G4-hemin self-assembly forFrontiers in chemistry · 2025Article
- Unraveling the noncoding RNA landscape in glioblastoma: from pathogenesis to precision therapeutics.Naunyn-Schmiedeberg's archives of pharmacology · 2024Review
- Harnessing CRISPR/Cas Systems for DNA and RNA Detection: Principles, Techniques, and Challenges.Biosensors · 2024Review
- CRISPR-Cas target recognition for sensing viral and cancer biomarkers.Nucleic acids research · 2024Review
- Harnessing noncanonical crRNA for highly efficient genome editing.Nature communications · 2024Article
- Gene targeting in adult organs using in vivo cleavable donor plasmids for CRISPR-Cas9 and CRISPR-Cas12a.Scientific reports · 2024Article
- Sensing the DNA-mismatch tolerance of catalytically inactive Cas9 via barcoded DNA nanostructures in solid-state nanopores.Nature biomedical engineering · 2024Article
- Harnessing noncanonical crRNAs to improve functionality of Cas12a orthologs.Cell reports · 2024Article
- Regulation of the CRISPR-Cas12a system by methylation and demethylation of guide RNA.Chemical science · 2023Article
- Machine learning for design of degenerate Cas13a crRNAs using lassa virus as a model of highly variable RNA target.Scientific reports · 2023Article
- Article
- Computational analysis of cas proteins unlocks new potential in HIV-1 targeted gene therapy.Frontiers in genome editing · 2023Article
- Strategies for delivery of CRISPR/Cas-mediated genome editing to obtain edited plants directly without transgene integration.Frontiers in genome editing · 2023Review
- Development of an in vivo cleavable donor plasmid for targeted transgene integration by CRISPR-Cas9 and CRISPR-Cas12a.Scientific reports · 2022Article
- Comparison of CRISPR Sequences in Archaea and Bacteria with Eukaryotic microRNAs.Avicenna journal of medical biotechnologyArticle
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
CRISPR/Cas complexes enable precise gene editing in a wide variety of organisms. While the rigid identification of DNA sequences by these systems minimizes the potential for off-target effects, it consequently poses a problem for the recognition of sequences containing naturally occurring polymorphisms. The presence of genetic variance such as single nucleotide polymorphisms (SNPs) in a gene sequence can compromise the on-target activity of CRISPR systems. Thus, when attempting to target multiple variants of a human gene, or evolved variants of a pathogen gene using a single guide RNA, more flexibility is desirable. Here, we demonstrate that Cas9 can tolerate the inclusion of universal bases in individual guide RNAs, enabling simultaneous targeting of polymorphic sequences. Crucially, we find that specificity is selectively degenerate at the site of universal base incorporation, and remains otherwise preserved. We demonstrate the applicability of this technology to targeting multiple naturally occurring human SNPs with individual guide RNAs and to the design of Cas12a/Cpf1-based DETECTR probes capable of identifying multiple evolved variants of the HIV protease gene. Our findings extend the targeting capabilities of CRISPR/Cas systems beyond their canonical spacer sequences and highlight a use of natural and synthetic universal bases.
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Registered trials
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.