Effective transduction by self‐complementary adeno‐associated viruses of human dendritic cells with no alteration of their natural characteristics

Shin, Ohkyu; Kim, Sung Jin; Lee, Won Il; Kim, Jee Yeon; Lee, Heuiran

doi:10.1002/jgm.1204

Cited by 16 publications

(12 citation statements)

References 39 publications

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“…In a subsequent assessment with cells from three donors rAAV2/6 mean transduction levels at an MOI of 10 5 per cell reached 13.8% compared with 3.6% for rAAV2 and 1.3% for rAAV2/1. Significant donor-to-donor variation was observed with all serotypes, consistent with previous studies (Ponnazhagan et al, 2001;Shin et al, 2008).…”

Section: Discussionsupporting

confidence: 91%

“…We assessed the immunophenotype of MoDCs transduced with rAAV2/6 (Y731F) and found only minor upregulation of CD86 and other markers of maturation (HLA-DRa and CD83; Fig. 4A and B), consistent with previous findings (Veron et al, 2007;Shin et al, 2008). Dendritic cells mature in response to signals via innate pathogen recognition receptors, such as the Tolllike receptors (TLRs) (Banchereau et al, 2000).…”

Section: Raav6 For Transduction Of Human Dcssupporting

confidence: 68%

“…A comparison of AAV serotypes in human and mouse DCs revealed rAAV5/5 to be significantly more effective than rAAV2 and all other serotypes tested (serotypes 1, 2, 5, 7, and 8) (Xin et al, 2006). Most recently, a comparison of self-complementary vectors pseudotyped with serotypes 1-8 identified rAAV serotypes 2, 5, and 6 as possessing a similarly high transduction ability (>20%) even at an MOI 100-fold lower than in the studies mentioned previously (Shin et al, 2008). Notably, Shin and colleagues assessed eGFP expression at 4 days postinfection whereas our assessments were made at 48 hr.…”

Section: Raav6 For Transduction Of Human Dcsmentioning

confidence: 81%

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Optimized Transduction of Human Monocyte-Derived Dendritic Cells by Recombinant Adeno-Associated Virus Serotype 6

Ussher

Taylor

2010

Human Gene Therapy

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Dendritic cells are the key antigen-presenting cells involved in the initiation of the adaptive immune response. Recombinant adeno-associated viruses (rAAVs) can transduce dendritic cells and have gained attention as potential vaccines capable of stimulating T cell immunity. Here we show that rAAV2 pseudotyped with type 6 capsid (rAAV2/6) exhibits significantly higher tropism for human monocyte-derived dendritic cells (MoDCs) than other serotypes and variants. Transduction was abolished by a single lysine-to-alanine mutation within the AAV6 capsid previously shown to inhibit binding to heparin. However, unlike rAAV2, soluble heparin did not inhibit rAAV2/6 transduction of MoDCs. Further enhancement of MoDC transduction was observed after mutation of Tyr-731 in the capsid of AAV6 consistent with a report that tyrosine residues are phosphorylated, leading to ubiquitination of capsids during uptake. Pseudotyped rAAV2/6 vectors containing a Y731F mutation minimally altered the immunophenotype of MoDCs, which retained their immunostimulatory ability and were able to stimulate an antigen-specific CD8(+) T cell clone. These findings should assist in the development of rAAV2/6 as a vaccine vector.

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Section: Discussionsupporting

confidence: 91%

Section: Raav6 For Transduction Of Human Dcssupporting

confidence: 68%

Section: Raav6 For Transduction Of Human Dcsmentioning

confidence: 81%

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Optimized Transduction of Human Monocyte-Derived Dendritic Cells by Recombinant Adeno-Associated Virus Serotype 6

Ussher

Taylor

2010

Human Gene Therapy

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“…They combine several advantageous features, including a good safety profile, stable long-term gene expression in several tissues, the ability to transduce dividing and nondividing cells, and physicochemical stability (11,66). AAV vectors show generally a low innate immunity, as well as low efficiency to transduce professional antigen-presenting cells (87), although recent studies warrant a more differentiated view of the immune response to AAV-mediated gene transfer (8,22,23,26,29,32,33,37,50,65,84,88). Humoral immune responses are generated and memory CD8 ϩ T-cell responses have been observed in clinical trials (36,40,58).…”

mentioning

confidence: 99%

The Threefold Protrusions of Adeno-Associated Virus Type 8 Are Involved in Cell Surface Targeting as Well as Postattachment Processing

Raupp

Naumer

Müller

et al. 2012

J Virol

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Adeno-associated virus (AAV) has attracted considerable interest as a vector for gene therapy owing its lack of pathogenicity and the wealth of available serotypes with distinct tissue tropisms. One of the most promising isolates for vector development, based on its superior gene transfer efficiency to the liver in small animals compared to AAV type 2 (AAV2), is AAV8. Comparison of the in vivo gene transduction of rAAV2 and rAAV8 in mice showed that single amino acid exchanges in the 3-fold protrusions of AAV8 in the surface loops comprised of residues 581 to 584 and 589 to 592 to the corresponding amino acids of AAV2 and vice versa had a strong influence on transduction efficiency and tissue tropism. Surprisingly, not only did conversion of AAV8 to AAV2 cap sequences increase the transduction efficiency and change tissue tropism but so did the reciprocal conversion of AAV2 to AAV8. Insertion of new peptide motifs at position 590 in AAV8 also enabled retargeting of AAV8 capsids to specific tissues, suggesting that these sequences can interact with receptors on the cell surface. However, a neutralizing monoclonal antibody that binds to amino acids 588 QQNTA 592 of AAV8 does not prevent cell binding and virus uptake, indicating that this region is not necessary for receptor binding but rather that the antibody interferes with an essential step of postattachment processing in which the 3-fold protrusion is also involved. This study supports a multifunctional role of the 3-fold region of AAV capsids in the infection process.

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“…Therefore, the final product was the mutant sc39TK cassette in rAAV2 genome. the generation, preparation, and titration of the rAAV2 vector were performed according to the method outlined previously (21).…”

Section: Methodsmentioning

confidence: 99%

Persistent anti-tumor effects via recombinant adeno-associated virus encoding herpes thymidine kinase gene monitored by PET-imaging

Kim

Kim²,

Khim³

et al. 2011

Oncol Rep

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Effective transduction by self‐complementary adeno‐associated viruses of human dendritic cells with no alteration of their natural characteristics

Abstract: These findings strongly indicate that scAAVs, especially subtypes 2, 5 and 6, hold a promising potential as gene delivery tools in human DCs.

Cited by 16 publications

References 39 publications

Optimized Transduction of Human Monocyte-Derived Dendritic Cells by Recombinant Adeno-Associated Virus Serotype 6

Optimized Transduction of Human Monocyte-Derived Dendritic Cells by Recombinant Adeno-Associated Virus Serotype 6

The Threefold Protrusions of Adeno-Associated Virus Type 8 Are Involved in Cell Surface Targeting as Well as Postattachment Processing

Persistent anti-tumor effects via recombinant adeno-associated virus encoding herpes thymidine kinase gene monitored by PET-imaging

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