ArticleGene therapy2007
Differential internalization and nuclear uncoating of self-complementary adeno-associated virus pseudotype vectors as determinants of cardiac cell transduction.
Article in Gene therapy, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 41 citations in OpenAlex.
- Review
- A novel class of self-complementary AAV vectors with multiple advantages based on cceAAV lacking mutant ITR.Molecular therapy. Methods & clinical development · 2024Article
- Adeno-associated virus type 2 (AAV2) uncoating is a stepwise process and is linked to structural reorganization of the nucleolus.PLoS pathogens · 2022Article
- Gene Transfer in Adeno-Associated Virus Seropositive Rhesus Macaques Following Rapamycin Treatment and Subcutaneous Delivery of AAV6, but Not Retargeted AAV6 Vectors.Human gene therapy · 2021Article
- Gene Therapy Preserves Retinal Structure and Function in a Mouse Model ofMolecular therapy. Methods & clinical development · 2020Article
- Effects of Thermally Induced Configuration Changes on rAAV Genome's Enzymatic Accessibility.Molecular therapy. Methods & clinical development · 2020Article
- Cell-specific CRISPR-Cas9 activation by microRNA-dependent expression of anti-CRISPR proteins.Nucleic acids research · 2019Article
- Reverse transduction can improve efficiency of AAV vectors in transduction-resistant cells.Biotechnology and bioengineering · 2018Article
- Myoediting: Toward Prevention of Muscular Dystrophy by Therapeutic Genome Editing.Physiological reviews · 2018Review
- Adeno-Associated Virus Vectors and Stem Cells: Friends or Foes?Human gene therapy · 2017Review
- Genome-wide computational analysis reveals cardiomyocyte-specific transcriptional Cis-regulatory motifs that enable efficient cardiac gene therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2015Article
- Recombinant adeno-associated virus utilizes cell-specific infectious entry mechanisms.Journal of virology · 2014Article
- Article
- Terminal differentiation of cardiac and skeletal myocytes induces permissivity to AAV transduction by relieving inhibition imposed by DNA damage response proteins.Molecular therapy : the journal of the American Society of Gene Therapy · 2012Article
- Intracellular transport of recombinant adeno-associated virus vectors.Gene therapy · 2012Review
- Gene therapy for heart failure.Circulation research · 2012Review
- Unique characteristics of AAV1, 2, and 5 viral entry, intracellular trafficking, and nuclear import define transduction efficiency in HeLa cells.Human gene therapy · 2011Article
- Self-complementary adeno-associated viral vectors for gene therapy of hemophilia B: progress and challenges.Expert review of hematology · 2011Review
- microRNA122-regulated transgene expression increases specificity of cardiac gene transfer upon intravenous delivery of AAV9 vectors.Gene therapy · 2011Article
- RH10 provides superior transgene expression in mice when compared with natural AAV serotypes for neonatal gene therapy.The journal of gene medicine · 2010Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recently it was shown that several new pseudotyped adeno-associated virus (AAV) vectors support cardioselective expression of transgenes. The molecular mechanisms underlying this propensity for cardiac cell transduction are not well understood. We comparatively analyzed AAV vector attachment, internalization, intracellular trafficking, and nuclear uncoating of recombinant self-complementary (sc) AAV2.2 versus pseudotyped scAAV2.6 vectors expressing green fluorescence protein (GFP) in cells of cardiac origin. In cardiac-derived HL-1 cells and primary neonatal rat cardiomyocytes (PNCMs), expression of GFP increased rapidly after incubation with scAAV2.6-GFP, but remained low after scAAV2.2-GFP. Internalization of scAAV2.6-GFP was more efficient than that of scAAV2.2-GFP. Nuclear translocation was similarly efficient for both, but differential nuclear uncoating rates emerged as a key additional determinant of transduction: 30% of all scAAV2.6-GFP genomes translocated to the nucleus became uncoated within 48 h, but only 16% of scAAV2.2-GFP genomes. In contrast to this situation in cells of cardiac origin, scAAV2.2-GFP displayed more efficient internalization and similar (tumor cell line HeLa) or higher (human microvascular endothelial cell (HMEC)) uncoating rates than scAAV.2.6-GFP in non-cardiac cell types. In summary, both internalization and nuclear uncoating are key determinants of cardiac transduction by scAAV2.6 vectors. Any in vitro screening for the AAV pseudotype most suitable for cardiac gene therapy - which is desirable since it may allow significant reductions in vector load in upcoming clinical trials--needs to quantitate both key steps in transduction.
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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.