Pseudotyping the adenovirus serotype 5 capsid with both the fibre and penton of serotype 35 enhances vascular smooth muscle cell transduction.
Pseudotyping the adenovirus serotype 5 capsid with both the fibre and penton of serotype 35 enhances vascular smooth muscle cell transduction.
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DOI：
10.1038/gt.2013.44
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发表时间：
2013-12
期刊：
影响因子：
5.1
通讯作者：
Baker, A. H.
中科院分区：
文献类型：
--
作者：
Parker, A. L.;White, K. M.;Lavery, C. A.;Custers, J.;Waddington, S. N.;Baker, A. H.
关键词：
冠状动脉旁路移植术（CABG）中的离体基因治疗在防止平滑肌细胞（SMC）过度增殖、新生内膜形成和移植物失败方面具有巨大潜力。迄今为止，最成功的临床前策略利用了基于C腺病毒Ad 5的载体，其接合科萨基和腺病毒受体（CAR）作为其主要附着受体。对人SMC上的受体进行分析表明不存在CAR，但物质B受体CD 46大量表达。我们使用Ad 5和利用CD 46的腺病毒Ad 35进行了转导实验，发现Ad 35在转导SMC方面显著更有效。为了评估转导是否可以进一步增强，我们评估了嵌合的利用CD 46的Ad 5/Ad 35载体，其包含用单独的Ad 35纤维假型化的Ad 5衣壳（Ad 5/F35）或与Ad 35五邻体组合的Ad 5衣壳（Ad 5/F35/P35）。在人平滑肌细胞（hSMCs）中，Ad 5/F35/P35介导的转导水平显著高于亲本载体或Ad 5/F35。使用来自CD 46转基因的小鼠腹水的离体转导实验证明，Ad 5/F35/P35在转导SMC方面比测试的其他载体显著更有效。最后，离体转导和免疫荧光共定位实验，使用人体组织从冠状动脉旁路移植术程序证实了临床前的潜力，Ad 5/F35/P35作为一个有效的载体血管转导在冠状动脉旁路移植术。
Ex vivo gene therapy during coronary artery bypass grafting (CABG) holds great potential to prevent excessive smooth muscle cell (SMC) proliferation, neointima formation and graft failure. The most successful preclinical strategies to date have utilised vectors based on the species C adenovirus, Ad5, which engages the Coxsackie and Adenovirus receptor (CAR) as its primary attachment receptor. Profiling receptors on human SMCs demonstrated the absence of CAR but substantial expression of the species B receptor CD46. We performed transduction experiments using Ad5 and the CD46-utilising adenovirus Ad35, and found Ad35 significantly more efficient at transducing SMCs. To evaluate whether transduction could be further augmented, we evaluated chimeric CD46-utilising Ad5/Ad35 vectors comprising the Ad5 capsid pseudotyped with the Ad35 fibre alone (Ad5/F35) or in combination with the Ad35 penton (Ad5/F35/P35). In human smooth muscle cells (hSMCs), Ad5/F35/P35 mediated significantly higher levels of transduction than either parental vector or Ad5/F35. Ex vivo transduction experiments using mouse aortas from CD46 transgenics demonstrated that Ad5/F35/P35 was significantly more efficient at transducing SMCs than the other vectors tested. Finally, ex vivo transduction and immunofluorescent colocalisation experiments using human tissue from CABG procedures confirmed the preclinical potential of Ad5/F35/P35 as an efficient vector for vascular transduction during CABG.
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影响因子：
82.9
作者：
Gaggar, A;Shayakhmetov, DM;Lieber, A
通讯作者：
Lieber, A
影响因子：
37.8
作者：
Roger VL;Go AS;Lloyd-Jones DM;Benjamin EJ;Berry JD;Borden WB;Bravata DM;Dai S;Ford ES;Fox CS;Fullerton HJ;Gillespie C;Hailpern SM;Heit JA;Howard VJ;Kissela BM;Kittner SJ;Lackland DT;Lichtman JH;Lisabeth LD;Makuc DM;Marcus GM;Marelli A;Matchar DB;Moy CS;Mozaffarian D;Mussolino ME;Nichol G;Paynter NP;Soliman EZ;Sorlie PD;Sotoodehnia N;Turan TN;Virani SS;Wong ND;Woo D;Turner MB;American Heart Association Statistics Committee and Stroke Statistics Subcommittee
通讯作者：
American Heart Association Statistics Committee and Stroke Statistics Subcommittee
影响因子：
5.4
作者：
Wang, Hongjie;Liaw, Yen-Chywan;Lieber, Andre
通讯作者：
Lieber, Andre
影响因子：
5.1
作者：
Akowuah, EF;Gray, C;Newman, CM
通讯作者：
Newman, CM
影响因子：
3.3
作者：
Hata, Mitsumasa;Sezai, Akira;Minami, Kazutomo
通讯作者：
Minami, Kazutomo