Endosomal processing limits gene transfer to polarized airway epithelia by adeno-associated virus

Duan, Dongsheng; Yue, Yongping; Yan, Ziying; Yang, Jusan; Engelhardt, John F.

doi:10.1172/jci8317

Cited by 354 publications

(403 citation statements)

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“…44 Although HSPG and aVb5 integrin are absent on the apical surface and abundant on the basolateral surface, there is only a slight difference (three-to five-fold) in the extent of AAV2 endocytosis from apical and basolateral compartments. 32,44 This observation suggests that there are likely other AAV2 internalization pathways independent of known AAV2 receptors, and that the entry pathways for AAV2 may significantly influence the efficiency of intracellular processing of the virus.…”

Section: Aav Attachment Receptors and Coreceptorsmentioning

confidence: 99%

“…18,43 Despite the fact that HSPG appears to be a major AAV2 attachment receptor for many cell types, other model systems have demonstrated considerable uptake of AAV2 in the absence of surface HSPG expression. 32,44 Hence, attachment receptors for AAV2 other than HSPG may also exist, but have yet to be identified. In contrast to AAV2 and AAV3, sialic acid has been identified as a primary attachment receptor for AAV4 and AAV5.…”

Section: Aav Attachment Receptors and Coreceptorsmentioning

confidence: 99%

Section: Receptor-mediated Endocytosis Of Aavmentioning

confidence: 99%

“…[32][33][34][35]66 The mechanism of enhanced transduction in the presence of proteasome inhibitors does not appear to be due to blocking AAV genome degradation. 32,66 Rather, inhibition of the proteasome enhances nuclear uptake of viruses in a number of cell systems. 32,35 These findings suggest that modulation of the ubiquitinproteasome system might alter AAV intracellular processing at the level of endosomal trafficking, endosomal escape, nuclear transport, and/or uncoating of the virus.…”

Section: Receptor-mediated Endocytosis Of Aavmentioning

confidence: 99%

“…Increasing evidence has suggested that intracellular trafficking of rAAV may be a universal rate-limiting step in AAV transduction. [32][33][34][35][36][37][38] However, entry pathways of AAVs likely determine the paths by which these viruses move through the cell to the nucleus. As such, discussions of intracellular trafficking must be placed in the context of viral receptors and coreceptors that facilitate endocytosis and movement of AAVs through the endosomal compartment.…”

Section: Introductionmentioning

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: Aav Attachment Receptors and Coreceptorsmentioning

confidence: 99%

Section: Aav Attachment Receptors and Coreceptorsmentioning

confidence: 99%

Section: Receptor-mediated Endocytosis Of Aavmentioning

confidence: 99%

Section: Receptor-mediated Endocytosis Of Aavmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Intracellular trafficking of adeno-associated viral vectors

et al. 2005

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Gene Delivery to the Airway

Keiser

Engelhardt

2013

CP Human Genetics

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This unit describes generation of and gene transfer to several commonly used airway models. Isolation and transduction of primary airway epithelial cells are first described. Next, the preparation of polarized airway epithelial monolayers is outlined. Transduction of these polarized cells is also described. Methods are presented for generation of tracheal xenografts as well as both ex vivo and in vivo gene transfer to these xenografts. Finally, a method for in vivo gene delivery to the lungs of rodents is included. Methods for evaluating transgene expression are given in the support protocols.

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The State of the Art and Future of Gene Medicines

Jacobs¹,

Gordts²,

Geest³

2013

Pharmaceutical Sciences Encyclopedia

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In this chapter, we will discuss the significant technological progress that has been made in the development of gene therapy strategies and the application of these strategies in specific therapeutic niches. More specifically, we aim to provide an overview of selected highlights from the past (preclinical development), current (first‐in‐man clinical trials), and future (remaining hurdles and regulatory aspects) of different gene therapy approaches. In these discussions, we will focus on gene therapy approaches using viral vectors because they are generally considered to be more efficacious and have yielded the most prominent clinical successes.

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Endosomal processing limits gene transfer to polarized airway epithelia by adeno-associated virus

Cited by 354 publications

References 40 publications

Intracellular trafficking of adeno-associated viral vectors

Intracellular trafficking of adeno-associated viral vectors

Gene Delivery to the Airway

The State of the Art and Future of Gene Medicines

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