ArticleNucleic acids research2011
Directed adenovirus evolution using engineered mutator viral polymerases.
Article in Nucleic acids research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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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
21 citing papers in PubMed, 32 citations in OpenAlex.
- Anti-CRISPR-mediated continuous directed evolution of CRISPR-Cas9 in human cells.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Anti-CRISPR-mediated continuous directed evolution of CRISPR-Cas9 in human cells.bioRxiv : the preprint server for biology · 2025Article
- Combining CRISPR-Cas-mediated terminal resolution with a novel genetic workflow to achieve high-diversity adenoviral libraries.Molecular therapy. Methods & clinical development · 2024Article
- Fast Track Adaptation of Oncolytic Coxsackie B3 Virus to Resistant Colorectal Cancer Cells - a Method to Personalize Virotherapy.Biological procedures online · 2024Article
- Expanding the Scope of Adenoviral Vectors by Utilizing Novel Tools for Recombination and Vector Rescue.Viruses · 2024Article
- Genetic diversity of adenovirus in neotropical bats from Brazil.Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology] · 2023Article
- Virus-assisted directed evolution of biomolecules.Current opinion in chemical biology · 2023Review
- Self-attenuating adenovirus enables production of recombinant adeno-associated virus for high manufacturing yield without contamination.Nature communications · 2022Article
- Genetic Modifications That Expand Oncolytic Virus Potency.Frontiers in molecular biosciences · 2022Review
- Directed evolution in mammalian cells.Nature methods · 2021Review
- Article
- Genetic Engineering by DNA Recombineering.Current protocols in chemical biology · 2019Article
- An Adaptable Platform for Directed Evolution in Human Cells.Journal of the American Chemical Society · 2018Article
- Current Experimental Studies of Gene Therapy in Parkinson's Disease.Frontiers in aging neuroscience · 2017Review
- Changing faces in virology: the dutch shift from oncogenic to oncolytic viruses.Human gene therapy · 2014Review
- An orthogonal DNA replication system in yeast.Nature chemical biology · 2014Article
- Experimental evolution of an oncolytic vesicular stomatitis virus with increased selectivity for p53-deficient cells.PloS one · 2014Article
- Directed evolution of mutator adenoviruses resistant to antibody neutralization.Journal of virology · 2013Article
- Adenovirus DNA replication.Cold Spring Harbor perspectives in biology · 2013Review
- A cathepsin-cleavage site between the adenovirus capsid protein IX and a tumor-targeting ligand improves targeted transduction.Gene therapy · 2012Article
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 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Adenoviruses (Ads) are the most frequently used viruses for oncolytic and gene therapy purposes. Most Ad-based vectors have been generated through rational design. Although this led to significant vector improvements, it is often hampered by an insufficient understanding of Ad's intricate functions and interactions. Here, to evade this issue, we adopted a novel, mutator Ad polymerase-based, 'accelerated-evolution' approach that can serve as general method to generate or optimize adenoviral vectors. First, we site specifically substituted Ad polymerase residues located in either the nucleotide binding pocket or the exonuclease domain. This yielded several polymerase mutants that, while fully supportive of viral replication, increased Ad's intrinsic mutation rate. Mutator activities of these mutants were revealed by performing deep sequencing on pools of replicated viruses. The strongest identified mutators carried replacements of residues implicated in ssDNA binding at the exonuclease active site. Next, we exploited these mutators to generate the genetic diversity required for directed Ad evolution. Using this new forward genetics approach, we isolated viral mutants with improved cytolytic activity. These mutants revealed a common mutation in a splice acceptor site preceding the gene for the adenovirus death protein (ADP). Accordingly, the isolated viruses showed high and untimely expression of ADP, correlating with a severe deregulation of E3 transcript splicing.
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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.