Cell-Type-Specific Characteristics Modulate the Transduction Efficiency of Adeno-Associated Virus Type 2 and Restrain Infection of Endothelial Cells

Pajusola, Katri; Gruchała, Marcin; Joch, Hana; Lüscher, Thomas F.; Ylä‐Herttuala, Seppo; Büeler, Hansruedi

doi:10.1128/jvi.76.22.11530-11540.2002

Cited by 92 publications

(88 citation statements)

References 41 publications

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“…For example, movement to the Golgi compartment can be facilitated through either the Rab11 PNRE or the Rab7-Rab9 late endosomal pathway (Figure 3). Cell line-dependent differences in trafficking of AAV have also been reported, 65 and suggest that AAV can traverse several endosomal pathways. Furthermore, studies solely evaluating localization and bulk flow of AAV through the cell do not directly address what endosomal compartments are most important for functional processing of virions or the point of endosomal escape.…”

Section: Receptor-mediated Endocytosis Of Aavmentioning

confidence: 96%

“…Several laboratories have demonstrated that when acidification of the endosomal compartment is blocked by bafilomycin A1, transduction with rAAV2 is significantly decreased. 33,38,65 However, a requirement for acidification within the endosomal compartment also demonstrates cell-type specificities. 38,65 Furthermore, acidification alone is not sufficient to promote transduction with CPV as demonstrated by microinjecting particles pretreated at pH 5.0.…”

Section: Receptor-mediated Endocytosis Of Aavmentioning

confidence: 99%

“…33,38,65 However, a requirement for acidification within the endosomal compartment also demonstrates cell-type specificities. 38,65 Furthermore, acidification alone is not sufficient to promote transduction with CPV as demonstrated by microinjecting particles pretreated at pH 5.0. 64 Whether the AAV capsids are modified on the virion, while within the endosomal compartment, remains to be directly proven.…”

Section: Receptor-mediated Endocytosis Of Aavmentioning

confidence: 99%

“…34,35 Furthermore, there appears to be some level of cell-type specificity in the action of proteasome inhibitors since they do not enhance rAAV transduction in all cell types and tissues. 32,65 Although the mechanism of proteasome inhibitor action remains unclear, the finding that both rAAV2 and rAAV5 capsids are a substrate for ubiquitination in vivo and in vitro 32,66 suggests that the extent of capsid ubiquitination may be important in directing intracellular movement of the virion. Furthermore, in vitro ubiquitination assays have demonstrated that partially denatured purified AAV virions are preferred substrates for ubiquitination.…”

Section: Receptor-mediated Endocytosis Of Aavmentioning

confidence: 99%

“…36 Lastly, it has also been suggested that both AAV2 and AAV5 traffic to the trans-Golgi network. 60,65 Although at face value it appears that results on AAV vesicular trafficking remain controversial, the results between laboratories are not entirely inconsistent. For example, movement to the Golgi compartment can be facilitated through either the Rab11 PNRE or the Rab7-Rab9 late endosomal pathway (Figure 3).…”

Section: Receptor-mediated Endocytosis Of Aavmentioning

confidence: 99%

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Intracellular trafficking of adeno-associated viral vectors

et al. 2005

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Adeno-associated virus (AAV) has attracted considerable interest as a gene therapy vector over the past decade. In all, 85% of the current 2052 PubMed references on AAV (as of December 2004) have been published in the last 10 years. As researchers have moved forward with using this vector system for gene delivery, an increased appreciation for the complexities of AAV biology has emerged. The biology of recombinant AAV (rAAV) transduction has demonstrated considerable diversity in different cell types and target tissues. This review will summarize the current understanding of events that control rAAV transduction following receptor binding and leading to nuclear uptake. These stages are broadly classified as intracellular trafficking and have been found to be a major rate-limiting step in rAAV transduction for many cell types. Advances in understanding this area of rAAV biology will help to improve the efficacy of this vector system for the treatment of inherited and acquired diseases. Gene Therapy (2005) 12, 873-880.

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Section: Receptor-mediated Endocytosis Of Aavmentioning

confidence: 96%

Section: Receptor-mediated Endocytosis Of Aavmentioning

confidence: 99%

Section: Receptor-mediated Endocytosis Of Aavmentioning

confidence: 99%

Section: Receptor-mediated Endocytosis Of Aavmentioning

confidence: 99%

Section: Receptor-mediated Endocytosis Of Aavmentioning

confidence: 99%

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Intracellular trafficking of adeno-associated viral vectors

et al. 2005

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Substrate Stiffness and Particle Properties Influence Cellular Uptake of Nanoparticles and Viruses from the Ventral Side

Voigt,

Timmer,

Pennarola

et al. 2023

Adv Funct Materials

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It is a long‐standing challenge to exploit cellular uptake mechanisms to deliver desired cargo into cells, for example, specific drugs or gene editing techniques. This study introduces a bioinspired material approach where nanoparticles are presented at the ventral side of cells adhering to engineered extracellular matrices. The effect of matrix stiffness on cell adhesion and mechanics, as well as on particle internalization by clathrin‐mediated endocytosis (CME), is investigated for varying particle size and surface functionalization. The results presented here show that substrate stiffness affects both cell adhesion and particle internalization, with softer substrates promoting higher levels of particle uptake. However, the activation of the CME pathway, either mechanically by particle size or functionally by receptor binding, regulates the sensitivity of cellular particle uptake to matrix stiffness. Finally, adeno‐associated viruses as the leading platform for therapeutic gene delivery are used as model cargo to showcase the importance of considering multiple components when designing delivery systems. These findings indicate that particle uptake is a multifaceted process that can be improved by the appropriate combination of extracellular environment mechanics and cargo properties.

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