ArticleMolecular therapy : the journal of the American Society of Gene Therapy2006
rAAV2 traffics through both the late and the recycling endosomes in a dose-dependent fashion.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 96 citations in OpenAlex.
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- Suppressing microtubule detyrosination augments adeno-associated virus 2 endosomal escape and gene delivery.Journal of cell science · 2025Article
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- Identification of SLC35A1 as an essential host factor for the transduction of multi-serotype recombinant adeno-associated virus (AAV) vectors.bioRxiv : the preprint server for biology · 2024Article
- Temporal insights into molecular and cellular responses during rAAV production in HEK293T cells.Molecular therapy. Methods & clinical development · 2024Article
- Recombinant Adeno-Associated Virus Vectors for Gene Therapy of the Central Nervous System: Delivery Routes and Clinical Aspects.Biomedicines · 2024Review
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- Predicted deleterious variants in the human genome relevant to gene therapy with adeno-associated virus vectors.Molecular therapy. Methods & clinical development · 2023Article
- The significance of triple-capsid-mutant AAV8 for treatment of Sanfilippo Syndrome Type B.Archives of stem cell and therapy · 2022Article
- Intracellular trafficking of adeno-associated virus (AAV) vectors: challenges and future directions.Gene therapy · 2021Review
- Answered and Unanswered Questions in Early-Stage Viral Vector Transduction Biology and Innate Primary Cell Toxicity forFrontiers in immunology · 2021Review
- Repeat Dosing of AAV2.5T to Ferret Lungs Elicits an Antibody Response That Diminishes Transduction in an Age-Dependent Manner.Molecular therapy. Methods & clinical development · 2020Article
- Adeno-Associated Virus (AAV) Capsid Stability and Liposome Remodeling During Endo/Lysosomal pH Trafficking.Viruses · 2020Article
- Viral Vectors, Animal Models, and Cellular Targets for Gene Therapy of Cystic Fibrosis Lung Disease.Human gene therapy · 2020Review
- Chemical modification of the adeno-associated virus capsid to improve gene delivery.Chemical science · 2019Article
- The hybrid AAVP tool gets an upgrade.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- A novel and highly efficient AAV6 mutant.Virus genes · 2018Article
- Proteasome Inhibition Increases the Efficiency of Lentiviral Vector-Mediated Transduction of Trabecular Meshwork.Investigative ophthalmology & visual science · 2018Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Inefficient trafficking of recombinant adeno-associated virus type-2 (rAAV2) to the nucleus is a major barrier for transduction. Using imaging and subcellular fractionation techniques, we evaluated the extent of rAAV2 movement through the late (Rab7) and recycling (Rab11) endosomes. Following rAAV2 infection of HeLa cells, immunoisolation of HA-Rab7- or HA-Rab11-tagged endosomes and intracellular colocalization of Cy3-labeled rAAV2 with EGFP-Rab7 or EGFP-Rab11 markers demonstrated dose-dependent trafficking of rAAV2 through the recycling and late endosomal compartments. At low multiplicities of infection (m.o.i. 100 genomes/cell), rAAV2 predominantly trafficked to the Rab7 compartment. In contrast, rAAV2 predominantly trafficked to the recycling endosome at 100-fold higher m.o.i. siRNA studies inhibiting either Rab7 or Rab11 demonstrated that reducing Rab11 protein levels more significantly inhibited rAAV2 transduction on a per genome basis compared to inhibition of Rab7. Dose-response curves, comparing the m.o.i. of AV2Luc infection to relative transduction, also supported the hypothesis that viral movement through the Rab11 compartment at high m.o.i. is more competent for transgene expression ( approximately 100-fold) than virus that moves through the Rab7 compartment at low m.o.i. These findings suggest that strategies to shunt viral movement from the late to the recycling endosome may be effective at increasing viral transduction for gene 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.