Gene therapy in the second eye of RPE65-deficient dogs improves retinal function.
Gene therapy in the second eye of RPE65-deficient dogs improves retinal function.
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作者：
本研究的目的是评估免疫反应是否干扰基因治疗救援，使用视网膜下递送的重组腺相关病毒载体血清型2，携带由人RPE65启动子（rAAV2.hRPE65p.hRPE65）驱动的RPE65 cDNA基因，在先前接受过类似治疗的RPE65−/−狗的第二只眼中。 另一只眼的方式。对 9 只狗进行双侧视网膜下注射，第二只眼在第一只眼后 85-180 天接受治疗。视网膜电图 (ERG) 和视力测试显示 18 只接受治疗的眼睛中有 16 只获得了挽救，第一只和第二只接受治疗的眼睛之间没有显着差异。在所有接受治疗的动物中均检测到对 rAAV2 的血清中和抗体 (NAb) 反应，但这并没有阻止或降低第二只接受治疗的眼睛的救援效果。我们得出的结论是，在第二只眼中使用视网膜下 rAAV2.hRPE65p.hRPE65 基因治疗的成功救援并不妨碍 RPE65−/− 狗对侧眼的先前基因治疗。这一发现对于人类 LCA II 型患者的治疗具有重要意义。
The purpose of this study was to evaluate whether immune responses interfered with gene therapy rescue using subretinally delivered recombinant adeno-associated viral vector serotype 2 carrying the RPE65 cDNA gene driven by the human RPE65 promoter (rAAV2.hRPE65p.hRPE65) in the second eye of RPE65−/− dogs that had previously been treated in a similar manner in the other eye. Bilateral subretinal injection was performed in nine dogs with the second eye treated 85–180 days after the first. Electroretinography (ERG) and vision testing showed rescue in 16 of 18 treated eyes, with no significant difference between first and second treated eyes. A serum neutralizing antibody (NAb) response to rAAV2 was detected in all treated animals, but this did not prevent or reduce the effectiveness of rescue in the second treated eye. We conclude that successful rescue using subretinal rAAV2.hRPE65p.hRPE65 gene therapy in the second eye is not precluded by prior gene therapy in the contralateral eye of the RPE65−/− dog. This finding has important implications for the treatment of human LCA type II patients.
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DOI：
10.1073/pnas.0601433103
发表时间：
2006-08-29
影响因子：
11.1
作者：
Limberis, Maria P.;Wilson, James M.
通讯作者：
Wilson, James M.
影响因子：
5.4
作者：
Halbert, CL;Standaert, TA;Miller, AD
通讯作者：
Miller, AD
影响因子：
1.4
作者：
Narfström, K;Vaegan;Seeliger, M
通讯作者：
Seeliger, M
影响因子：
3.5
作者：
Barker, Susie E.;Broderick, Cathryn A.;Robbie, Scott J.;Duran, Yanai;Natkunarajah, Mythili;Buch, Prateek;Balaggan, Kamaljit S.;MacLaren, Robert E.;Bainbridge, James W. B.;Smith, Alexander J.;Ali, Robin R.
通讯作者：
Ali, Robin R.
影响因子：
4.2
作者：
Hauswirth, William W.;Aleman, Tomas S.;Jacobson, Samuel G.
通讯作者：
Jacobson, Samuel G.