ArticleProceedings of the National Academy of Sciences of the United States of America2011
Computationally designed adeno-associated virus (AAV) Rep 78 is efficiently maintained within an adenovirus vector.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 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
12 citing papers in PubMed, 25 citations in OpenAlex.
- Interferon-γ inducible factor 16 (IFI16) restricts adeno-associated virus type 2 (AAV2) transduction in an immune-modulatory independent way.Journal of virology · 2024Article
- AAV- based vector improvements unrelated to capsid protein modification.Frontiers in medicine · 2023Review
- High-Level rAAV Vector Production by rAdV-Mediated Amplification of Small Amounts of Input Vector.Viruses · 2022Article
- Self-attenuating adenovirus enables production of recombinant adeno-associated virus for high manufacturing yield without contamination.Nature communications · 2022Article
- Compositional biases in RNA viruses: Causes, consequences and applications.Wiley interdisciplinary reviews. RNA · 2022Review
- Synonymous genome recoding: a tool to explore microbial biology and new therapeutic strategies.Nucleic acids research · 2019Review
- HIV-1 Protease Evolvability Is Affected by Synonymous Nucleotide Recoding.Journal of virology · 2018Article
- Efficiency and Specificity of Targeted Integration Mediated by the Adeno-Associated Virus Serotype 2 Rep 78 Protein.Human gene therapy methods · 2018Article
- A Regulatory Element Near the 3' End of the Adeno-Associated Virus rep Gene Inhibits Adenovirus Replication in cis by Means of p40 Promoter-Associated Short Transcripts.Journal of virology · 2016Article
- Differential contribution of adeno-associated virus type 2 Rep protein expression and nucleic acid elements to inhibition of adenoviral replication in cis and in trans.Journal of virology · 2014Article
- Changes in codon-pair bias of human immunodeficiency virus type 1 have profound effects on virus replication in cell culture.Retrovirology · 2013Article
- Identification of two functionally redundant RNA elements in the coding sequence of poliovirus using computer-generated design.Proceedings of the National Academy of Sciences of the United States of America · 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
8 authors at 2 institutions in 1 country.
Funding
Abstract
Adeno-associated virus (AAV) is a single-stranded parvovirus retaining the unique capacity for site-specific integration into a transcriptionally silent region of the human genome, a characteristic requiring the functional properties of the Rep 78/68 polypeptide in conjunction with AAV terminal repeat integrating elements. Previous strategies designed to assemble these genetic elements into adenoviral (Ad) backbones have been limited by the general intolerability of AAV Rep sequences, prompting us to computationally reengineer the Rep gene by using synonymous codon pair recoding. Rep mutants generated by using de novo genome synthesis maintained the polypeptide sequence and endonuclease properties of Rep 78, while dramatically enhancing Ad replication and viral titer yields, characteristics indistinguishable from adenovirus lacking coexpressed Rep. Parallel approaches using domain swaps encompassing WT and recoded genomic segments, coupled with iterative computational algorithms, collectively established that 3' cis-acting Rep genetic elements (and not the Rep 78 polypeptide) retain dominant-acting sequences inhibiting Ad replication. These data provide insights into the molecular relationships of AAV Rep and Ad replication, while expanding the applicability of synonymous codon pair reengineering as a strategy to effect phenotypic endpoints.
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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.