ArticleGene therapy2020
Integrating gene delivery and gene-editing technologies by adenoviral vector transfer of optimized CRISPR-Cas9 components.
Article in Gene therapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
38 citing papers in PubMed, 63 citations in OpenAlex.
- Discovery and engineering of retrons for precise genome editing.Nature biotechnology · 2026Article
- Integrating cells, scaffolds, and molecular regulation: a mechanobiological and translational review of bioengineering therapies for intervertebral disc degeneration.Frontiers in bioengineering and biotechnology · 2026Review
- CRISPR-Cas9: Transforming Functional Genomics, Precision Medicine, and Drug Development - Opportunities, Challenges, and Future Directions.Current gene therapy · 2026Review
- Enhancing Specificity, Precision, Accessibility, Flexibility, and Safety to Overcome Traditional CRISPR/Cas Editing Challenges and Shape Future Innovations.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Precision genome editing using combinatorial viral vector delivery of CRISPR-Cas9 nucleases and donor DNA constructs.Nucleic acids research · 2025Article
- Genome Editing Approaches Using Zinc Finger Nucleases (ZFNs) for the Treatment of Motor Neuron Diseases.Current pharmaceutical biotechnology · 2025Review
- AAV vector-derived elements integrate into Cas9-generated double-strand breaks and disrupt gene transcription.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Integrating Prime Editing and Cellular Reprogramming as Novel Strategies for Genetic Cardiac Disease Modeling and Treatment.Current cardiology reports · 2024Review
- Review
- Genetically encoding multiple functionalities into extracellular vesicles for the targeted delivery of biologics to T cells.Nature biomedical engineering · 2024Article
- Acoustically targeted noninvasive gene therapy in large brain volumes.Gene therapy · 2024Article
- Current Strategies for Increasing Knock-In Efficiency in CRISPR/Cas9-Based Approaches.International journal of molecular sciences · 2024Review
- Increasing Gene Editing Efficiency via CRISPR/Cas9- or Cas12a-Mediated Knock-In in Primary Human T Cells.Biomedicines · 2024Review
- Clinical applications of the CRISPR/Cas9 genome-editing system: Delivery options and challenges in precision medicine.Genes & diseases · 2024Review
- Lipid-Based Nanotechnology: Liposome.Pharmaceutics · 2023Review
- Silk Fibroin-Modified Liposome/Gene Editing System Knocks out thePharmaceutics · 2023Article
- Efficient Editing of the CXCR4 Locus Using Cas9 Ribonucleoprotein Complexes Stabilized with Polyglutamic Acid.Doklady biological sciences : proceedings of the Academy of Sciences of the USSR, Biological sciences sections · 2023Article
- Research progress and application of the CRISPR/Cas9 gene-editing technology based on hepatocellular carcinoma.Asian journal of pharmaceutical sciences · 2023Review
- High-capacity adenovector delivery of forced CRISPR-Cas9 heterodimers fosters precise chromosomal deletions in human cells.Molecular therapy. Nucleic acids · 2023Article
- Nonviral nanoparticle gene delivery into the CNS for neurological disorders and brain cancer applications.Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Enhancing the intracellular delivery and performance of RNA-guided CRISPR-Cas9 nucleases (RGNs) remains in demand. Here, we show that nuclear translocation of commonly used Streptococcus pyogenes Cas9 (SpCas9) proteins is suboptimal. Hence, we generated eCas9.4NLS by endowing the high-specificity eSpCas9(1.1) nuclease (eCas9.2NLS) with additional nuclear localization signals (NLSs). We demonstrate that eCas9.4NLS coupled to prototypic or optimized guide RNAs achieves efficient targeted DNA cleavage and probe the performance of SpCas9 proteins with different NLS compositions at target sequences embedded in heterochromatin versus euchromatin. Moreover, after adenoviral vector (AdV)-mediated transfer of SpCas9 expression units, unbiased quantitative immunofluorescence microscopy revealed 2.3-fold higher eCas9.4NLS nuclear enrichment levels than those observed for high-specificity eCas9.2NLS. This improved nuclear translocation yielded in turn robust gene editing after nonhomologous end joining repair of targeted double-stranded DNA breaks. In particular, AdV delivery of eCas9.4NLS into muscle progenitor cells resulted in significantly higher editing frequencies at defective DMD alleles causing Duchenne muscular dystrophy (DMD) than those achieved by AdVs encoding the parental, eCas9.2NLS, protein. In conclusion, this work provides a strong rationale for integrating viral vector and optimized gene-editing technologies to bring about enhanced RGN delivery and performance.
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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.