ArticleNature communications2019
An artificial triazole backbone linkage provides a split-and-click strategy to bioactive chemically modified CRISPR sgRNA.
Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
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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
27 citing papers in PubMed, 64 citations in OpenAlex.
- RNA chemistry and therapeutics.Nature reviews. Drug discovery · 2025Review
- Enhancing cap-independent translation of linear mRNA.Nature communications · 2025Article
- Chemical engineering of CRISPR-Cas systems for therapeutic application.Nature reviews. Drug discovery · 2025Review
- Viral and nonviral nanocarriers forNano research · 2024Article
- Emerging Gene Therapeutics for Epidermolysis Bullosa under Development.International journal of molecular sciences · 2024Review
- Triazole-linked Nucleic Acids: Synthesis, Therapeutics and Synthetic Biology Applications.Current organic synthesis · 2024Review
- Delivery of gene editing therapeutics.Nanomedicine : nanotechnology, biology, and medicine · 2023Review
- Designing Bioorthogonal Reactions for Biomedical Applications.Research (Washington, D.C.) · 2023Review
- Bio-Orthogonal Chemistry Conjugation Strategy Facilitates Investigation of N-methyladenosine and Thiouridine Guide RNA Modifications on CRISPR Activity.The CRISPR journal · 2022Article
- Affinity-Based Profiling of the Flavin Mononucleotide Riboswitch.Journal of the American Chemical Society · 2022Article
- Tetrazine-Ligated CRISPR sgRNAs for Efficient Genome Editing.ACS chemical biology · 2022Article
- 2'-Chemical science · 2022Article
- Artificial nucleic acid backbones and their applications in therapeutics, synthetic biology and biotechnology.Emerging topics in life sciences · 2021Article
- CRISPR-derived genome editing therapies: Progress from bench to bedside.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Review
- A New 1,5-Disubstituted Triazole DNA Backbone Mimic with Enhanced Polymerase Compatibility.Journal of the American Chemical Society · 2021Article
- Non-Chromatographic Purification of Synthetic RNA Using Bio-Orthogonal Chemistry.Current protocols · 2021Article
- Triazole-Modified Nucleic Acids for the Application in Bioorganic and Medicinal Chemistry.Biomedicines · 2021Review
- Modified Nucleosides, Nucleotides and Nucleic Acids via Click Azide-Alkyne Cycloaddition for Pharmacological Applications.Molecules (Basel, Switzerland) · 2021Review
- Modified internucleoside linkages for nuclease-resistant oligonucleotides.RSC chemical biology · 2021Review
- Strict conformational demands of RNA cleavage in bulge-loops created by peptidyl-oligonucleotide conjugates.Nucleic acids research · 2020Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
As the applications of CRISPR-Cas9 technology diversify and spread beyond the laboratory to diagnostic and therapeutic use, the demands of gRNA synthesis have increased and access to tailored gRNAs is now restrictive. Enzymatic routes are time-consuming, difficult to scale-up and suffer from polymerase-bias while existing chemical routes are inefficient. Here, we describe a split-and-click convergent chemical route to individual or pools of sgRNAs. The synthetic burden is reduced by splitting the sgRNA into a variable DNA/genome-targeting 20-mer, produced on-demand and in high purity, and a fixed Cas9-binding chemically-modified 79-mer, produced cost-effectively on large-scale, a strategy that provides access to site-specific modifications that enhance sgRNA activity and in vivo stability. Click ligation of the two components generates an artificial triazole linkage that is tolerated in functionally critical regions of the sgRNA and allows efficient DNA cleavage in vitro as well as gene-editing in cells with no unexpected off-target effects.
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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.