Serotype-specific transduction of canine joint tissue explants and cultured monolayers by self-complementary adeno-associated viral vectors

被引:0
|
作者
Kim, Ah Young [1 ]
Duerr, Felix Michael [1 ]
Phillips, Jennifer [1 ]
Samulski, Richard Jude [2 ,3 ]
Grieger, Josh C. [3 ]
Goodrich, Laurie R. [1 ]
机构
[1] Colorado State Univ, Coll Vet Med & Biomed Sci, Dept Clin Sci, 300 Drake Rd, Ft Collins, CO 80523 USA
[2] Gene Therapy Ctr, 7011 Thurston Bowles Bldg,104 Manning Dr, Chapel Hill, NC 27599 USA
[3] Asklepios Biopharmaceut Inc, 20 TW Alexander Dr 110, Res Triangle Pk, NC 27709 USA
关键词
MEDIATED GENE-THERAPY; NEUTRALIZING ANTIBODIES; AAV VECTORS; OSTEOARTHRITIS; EXPRESSION; DELIVERY; RECEPTOR; INJECTION;
D O I
10.1038/s41434-022-00366-x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
A formal screening of self-complementary adeno-associated virus (scAAV) vector serotypes in canine joint tissues has not been performed to date. Selecting appropriate serotypes is crucial for successful treatment due to their varying levels of tissue tropism. The objective of this study is to identify the most optimal scAAV vector serotype that maximizes transduction efficiencies in canine cell monolayer cultures (chondrocytes, synoviocytes, and mesenchymal stem cells) and tissue explant cultures (cartilage and synovium). Transduction efficiencies of scAAV serotypes 1, 2, 2.5, 3, 4, 5, 6, 8, and 9 were evaluated in each culture type in three different vector concentrations by encoding a green fluorescent protein. It was found that scAAV2 and 2.5 showed the overall highest transduction efficiency among serotypes with dose-response. Since possible immune response against conventional AAV2 was previously reported in dogs, the chimeric scAAV2.5 may be more suitable to use. Evaluation of the safety and efficacy of the scAAV2.5 vector with an appropriate therapeutic gene in vivo is indicated.
引用
收藏
页码:398 / 404
页数:7
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