Adeno-Associated Viral Vectors Show Serotype Specific Transduction of Equine Joint Tissue Explants and Cultured Monolayers

被引：17

作者：

Hemphill, Daniel D. ^{[1
]}

McIlwraith, C. Wayne ^{[1
]}

Samulski, R. Jude ^{[2
]}

Goodrich, Laurie R. ^{[1
]}

机构：

[1] Colorado State Univ, Coll Vet Med, Orthopaed Res Ctr, Ft Collins, CO 80523 USA

[2] Univ N Carolina, Gene Therapy Ctr, Chapel Hill, NC 27599 USA

来源：

SCIENTIFIC REPORTS | 2014年 / 4卷

关键词：

HEPARAN-SULFATE PROTEOGLYCAN; MEDIATED GENE-TRANSFER; GROWTH-FACTOR RECEPTOR; VIRUS AAV TYPE-2; SYNOVIAL-FLUID; SIALIC-ACID; IN-VIVO; EFFICIENT TRANSDUCTION; FACTOR-BETA; DELIVERY;

D O I：

10.1038/srep05861

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Adeno-associated virus (AAV) receptors range from heparan sulfate proteoglycan to sialic acid moieties present on cell surfaces. Abundance of the glycan profiles is greatly influenced by animal species, cell type, and culture conditions. The objective of this study was to determine whether AAV serotypes' transduction efficiencies specifically in the equine monolayer culture model are an accurate representation of transduction efficiencies in tissue explants, a model more closely related to in vivo transduction. It was found that AAV 2 and 2.5 transduced cells more efficiently in explants than in monolayers. Through experiments involving assessing enzyme degradation of cell surface proteoglycans, this change could not be attributed to differences in the extra cellular matrix (ECM), but a similar change in AAV 5 transduction efficiency could be readily explained by differences in cell surface sialylated glycan. Unexpectedly it was found that in a small but diverse sample of horses evidence for serum neutralizing antibodies was only found to AAV 5. This suggests a unique relationship between this capsid and the equine host or an unresolved relationship between similar bovine AAV and the AAV 5 capsid immune response.

引用

页数：7

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