Repeated administration of adenovector in the eye results in efficient gene delivery.
Repeated administration of adenovector in the eye results in efficient gene delivery.
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在眼中重复施用腺载体可实现有效的基因递送。
DOI：
10.1167/iovs.05-0731
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发表时间：
2006
期刊：
影响因子：
--
通讯作者：
Wei,LisaL
中科院分区：
文献类型：
--
作者：
Hamilton,MelissaM;Brough,DouglasE;McVey,Duncan;Bruder,JosephT;King,CRichter;Wei,LisaL
目的.为了确定腺病毒载体（Ad）重复施用到眼睛中是否导致有效的基因递送，并且为了测试转基因是否可以在预先存在的中和抗Ad抗体的存在下从腺病毒载体表达系统表达。为了评估腺病毒载体表达系统的重复基因递送的效率，C57 B1/6小鼠接受一次、两次或三次Adhesive注射（玻璃体内[IVT]或眼周[PO]）。11 D（空盒），随后是单个AdLuciferase（AdL. 11 D）IVT或PO注射。AdL后约24小时杀死小鼠。11 D注射，摘除眼睛并储存直至测定。还分析血清样品以确定重复IVT或PO注射是否导致针对腺载体递送系统的中和抗体的诱导。为了确定预先存在的中和性抗Ad抗体是否会阻断转基因表达，用一次、两次或三次肌内（IM）注射Adhesion对小鼠进行预免疫。11 D（1× 10 9粒子单位[pu]）。14天后，当预期存在全身性抗Ad抗体滴度时，给予小鼠单个AdL。11 D注射（IVT或PO）后处死，取眼及血清。这些研究表明，以2周间隔多次注射腺病毒载体（IM、IVT或PO）并不能阻止转基因在眼中的表达。此外，中和抗Ad抗体滴度的测量显示，可测量的抗Ad抗体滴度在小鼠中没有消融转基因表达。这些研究表明，重复腺病毒载体给药后转基因表达进入眼睛是可行的，重复注射，无论是给予IVT或PO，不会导致中和抗Ad抗体滴度的立即增加。此外，通过全身暴露于腺病毒载体的小鼠的预免疫不阻断眼睛中的转基因表达。这些研究表明，在设计未来的临床试验时可以考虑将腺病毒载体（IVT和PO）重复注入眼睛，并且中和抗Ad抗体的预先存在可能不会减轻活性。
purpose. To determine whether repeat administration of an adenovector (Ad) into the eye results in efficient gene delivery and to test whether transgenes can be expressed from an adenovector expression system in the presence of preexisting, neutralizing anti-Ad antibodies.methods. To assess the efficiency of repeated gene delivery of an adenovector expression system, C57Bl/6 mice received one, two, or three injections (intravitreal [IVT] or periocular [PO]) of AdNull. 11D (empty cassette) at 2-week intervals, followed by a single AdLuciferase (AdL. 11D) IVT or PO injection. Mice were killed approximately 24 hours after AdL. 11D injection and the eyes were enucleated and stored until assayed. Serum samples were also analyzed to determine whether repeated IVT or PO injections lead to induction of neutralizing antibodies directed against an adenovector delivery system. To determine whether preexisting neutralizing anti-Ad antibodies would block transgene expression, mice were preimmunized with one, two, or three intramuscular (IM) injection (s) of AdNull. 11D (1× 10 9 particle units [pu]). Fourteen days later, when systemic anti-Ad antibody titers were expected to exist, mice were given a single AdL. 11D injection (IVT or PO) and killed, and the eyes and serum collected.results. These studies show that multiple injections at 2-week intervals with adenovectors (IM, IVT, or PO) did not prevent transgene expression in the eye. Moreover, measurement of neutralizing anti-Ad antibody titers revealed that measurable anti-Ad antibody titers in mice did not ablate transgene expression.conclusions. These studies suggest that transgene expression after repeated adenovector administration into the eye is feasible and repeated injections, whether given IVT or PO, do not lead to an immediate increase in neutralizing anti-Ad antibody titers. Moreover, preimmunization of mice by systemic exposure to adenovector, does not block transgene expression in the eye. These studies indicate that repeat administration of adenovectors (IVT and PO) into the eye can be considered in designing future clinical trials and that the pre-existence of neutralizing anti-Ad antibodies probably does not mitigate activity.
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影响因子：
5.1
作者：
Kass-Eisler,A;Falck-Pedersen,E;Elfenbein,DH;Alvira,M;Buttrick,PM;Leinwand,LA
通讯作者：
Leinwand,LA
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影响因子：
5.1
作者：
Yiping Yang;K. Greenough;James M. Wilson
通讯作者：
James M. Wilson
增殖性视网膜病中眼内腺病毒载体介导的基因转移。
DOI：
--
发表时间：
2002
期刊：
Investigative ophthalmology & visual science.
影响因子：
--
作者：
Mori,Keisuke;Gehlbach,Peter;Ando,Akira;Wahlin,Karl;Gunther,Vicky;McVey,Duncan;Wei,Lisa;Campochiaro,PeterA
通讯作者：
Campochiaro,PeterA
DOI：
10.1073/pnas.91.10.4407
发表时间：
1994-05-10
影响因子：
11.1
作者：
YANG, YP;NUNES, FA;WILSON, JM
通讯作者：
WILSON, JM
重组 IL-12 可防止形成针对重组腺病毒的阻断性 IgA 抗体，并允许对小鼠肺进行重复基因治疗
影响因子：
82.9
作者：
Yiping Yang;G. Trinchieri;James M. Wilson
通讯作者：
James M. Wilson