ArticleInternational journal of molecular sciences2021
Adenovirus Vectors Expressing Eight Multiplex Guide RNAs of CRISPR/Cas9 Efficiently Disrupted Diverse Hepatitis B Virus Gene Derived from Heterogeneous Patient.
Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
What it found
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Who cites it
10 citing papers in PubMed, 20 citations in OpenAlex.
- Disruption of Human Papillomavirus 16 E6/E7 Genes Using All-in-One Adenovirus Vectors Expressing Eight Double-Nicking Guide RNAs.International journal of molecular sciences · 2025Article
- The Malignant Transformation of Viral Hepatitis to Hepatocellular Carcinoma: Mechanisms and Interventions.MedComm · 2025Review
- Emerging Gene-editing nano-therapeutics for Cancer.Heliyon · 2024Review
- Construction and Stability of All-in-One Adenovirus Vectors Simultaneously Expressing Four and Eight Multiplex Guide RNAs and Cas9 Nickase.International journal of molecular sciences · 2024Article
- Construction and application of adenoviral vectors.Molecular therapy. Nucleic acids · 2023Review
- Targeting miRNA by CRISPR/Cas in cancer: advantages and challenges.Military Medical Research · 2023Review
- Optimization of CRISPR-Cas system for clinical cancer therapy.Bioengineering & translational medicine · 2023Review
- Development of therapeutic vaccines for the treatment of diseases.Molecular biomedicine · 2022Review
- Review
- Advantages of CRISPR-Cas9 combined organoid model in the study of congenital nervous system malformations.Frontiers in bioengineering and biotechnology · 2022Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Hepatitis B virus (HBV) chronically infects more than 240 million people worldwide, causing chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). Genome editing using CRISPR/Cas9 could provide new therapies because it can directly disrupt HBV genomes. However, because HBV genome sequences are highly diverse, the identical target sequence of guide RNA (gRNA), 20 nucleotides in length, is not necessarily present intact in the target HBV DNA in heterogeneous patients. Consequently, possible genome-editing drugs would be effective only for limited numbers of patients. Here, we show that an adenovirus vector (AdV) bearing eight multiplex gRNA expression units could be constructed in one step and amplified to a level sufficient for in vivo study with lack of deletion. Using this AdV, HBV X gene integrated in HepG2 cell chromosome derived from a heterogeneous patient was cleaved at multiple sites and disrupted. Indeed, four targets out of eight could not be cleaved due to sequence mismatches, but the remaining four targets were cleaved, producing irreversible deletions. Accordingly, the diverse X gene was disrupted at more than 90% efficiency. AdV containing eight multiplex gRNA units not only offers multiple knockouts of genes, but could also solve the problems of heterogeneous targets and escape mutants in genome-editing therapy.
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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.