ArticlePLoS pathogens2015
The SUMOylation Pathway Restricts Gene Transduction by Adeno-Associated Viruses.
Article in PLoS pathogens, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 33 citations in OpenAlex.
- The Multifunctional SMC5/6 Complex in Genome Stability, Antiviral Restriction, and Human Disease.Current issues in molecular biology · 2026Review
- Small molecule inhibition of SUMOylation increases expression from AAV vectors both during and after initial transduction in mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- The role of post-translational modifications in parvovirus life cycle.Frontiers in veterinary science · 2025Review
- Gene Therapy in the Light of Lifestyle Diseases: Budesonide, Acetaminophen and Simvastatin Modulates rAAV Transduction Efficiency.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Characterization of AAV vectors: A review of analytical techniques and critical quality attributes.Molecular therapy. Methods & clinical development · 2024Review
- Genome-wide CRISPR screenings identified SMCHD1 as a host-restricting factor for AAV transduction.PLoS pathogens · 2024Article
- Predicted deleterious variants in the human genome relevant to gene therapy with adeno-associated virus vectors.Molecular therapy. Methods & clinical development · 2023Article
- The SMC5/6 complex: An emerging antiviral restriction factor that can silence episomal DNA.PLoS pathogens · 2023Article
- Review
- Adeno-associated virus (AAV) cell entry: structural insights.Trends in microbiology · 2022Review
- Intracellular trafficking of adeno-associated virus (AAV) vectors: challenges and future directions.Gene therapy · 2021Review
- Proteomic Landscape of Adeno-Associated Virus (AAV)-Producing HEK293 Cells.International journal of molecular sciences · 2021Article
- SUMOylation Targets Adeno-associated Virus Capsids but Mainly Restricts Transduction by Cellular Mechanisms.Journal of virology · 2020Article
- Exosome-associated SUMOylation mutant AAV demonstrates improved ocular gene transfer efficiency in vivo.Virus research · 2020Article
- Mouse adaptation of the H9N2 avian influenza virus causes the downregulation of genes related to innate immune responses and ubiquitin-mediated proteolysis in mice.Medical microbiology and immunology · 2020Article
- Increased Temperature Facilitates Adeno-Associated Virus Vector Transduction of Colorectal Cancer Cell Lines in a Manner Dependent on Heat Shock Protein Signature.BioMed research international · 2020Article
- Post-translational modifications in capsid proteins of recombinant adeno-associated virus (AAV) 1-rh10 serotypes.The FEBS journal · 2019Article
- Rational Engineering and Preclinical Evaluation of Neddylation and SUMOylation Site Modified Adeno-Associated Virus Vectors in Murine Models of Hemophilia B and Leber Congenital Amaurosis.Human gene therapy · 2019Article
- A CRISPR Screen Identifies the Cell Polarity Determinant Crumbs 3 as an Adeno-associated Virus Restriction Factor in Hepatocytes.Journal of virology · 2019Article
- Ring finger protein 121 is a potent regulator of adeno-associated viral genome transcription.PLoS pathogens · 2019Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Adeno-associated viruses are members of the genus dependoviruses of the parvoviridae family. AAV vectors are considered promising vectors for gene therapy and genetic vaccination as they can be easily produced, are highly stable and non-pathogenic. Nevertheless, transduction of cells in vitro and in vivo by AAV in the absence of a helper virus is comparatively inefficient requiring high multiplicity of infection. Several bottlenecks for AAV transduction have previously been described, including release from endosomes, nuclear transport and conversion of the single stranded DNA into a double stranded molecule. We hypothesized that the bottlenecks in AAV transduction are, in part, due to the presence of host cell restriction factors acting directly or indirectly on the AAV-mediated gene transduction. In order to identify such factors we performed a whole genome siRNA screen which identified a number of putative genes interfering with AAV gene transduction. A number of factors, yielding the highest scores, were identified as members of the SUMOylation pathway. We identified Ubc9, the E2 conjugating enzyme as well as Sae1 and Sae2, enzymes responsible for activating E1, as factors involved in restricting AAV. The restriction effect, mediated by these factors, was validated and reproduced independently. Our data indicate that SUMOylation targets entry of AAV capsids and not downstream processes of uncoating, including DNA single strand conversion or DNA damage signaling. We suggest that transiently targeting SUMOylation will enhance application of AAV in vitro and in vivo.
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