The potential of viral vector-mediated gene transfer to prolong corneal allograft survival.
The potential of viral vector-mediated gene transfer to prolong corneal allograft survival.
复制标题
病毒载体介导的基因转移延长角膜同种异体移植物存活的潜力。
DOI：
10.2174/156652309787354621
复制
发表时间：
2009
影响因子：
3.6
通讯作者：
K. Williams
中科院分区：
文献类型：
--
作者：
D. Parker;H. Brereton;D. Coster;K. Williams
角膜是一个特别有吸引力的基因治疗的目标，旨在改善角膜移植的结果。首先，有明确的临床需求。第二，因为供体角膜可以在眼库中保存数天（如果不是数周的话），所以可以进行供体角膜的离体转导，而没有与许多其他形式的移植相关的紧迫性。最后，眼睛与体循环的部分隔离降低了载体和转基因溢出的可能性，并且角膜和前段的免疫特权性质提供了一定程度的保护，免受针对载体的免疫反应。已经研究了广泛的载体用于基因转移到角膜。特别地，已经证明许多病毒载体在转导角膜方面是有效的，并且与各种转基因相结合，已经成功地用于在动物模型中显著延长角膜同种异体移植物的存活。最适合用于角膜移植的未来临床研究的此类载体尚未确定，但最有可能包括重组腺病毒、腺相关病毒和慢病毒载体。在这篇综述中，我们研究了这些病毒载体的能力，使角膜，并总结了这些研究中，基因治疗已被用于延长实验性角膜移植存活。
The cornea is a particularly attractive target for gene therapy designed to improve the outcome of corneal transplantation. First, there is a clear and well-defined clinical need. Second, because donor corneas can be preserved for days if not weeks within an eye bank, ex vivo transduction of a donor cornea can be carried out without the urgency associated with many other forms of transplantation. Finally, the partial sequestration of the eye from the systemic circulation decreases the likelihood of spillover of vector and transgene, and the immune privileged nature of the cornea and anterior segment affords a degree of protection from immune responses directed against the vector. A wide range of vectors has been investigated for gene transfer to the cornea. A number of viral vectors, in particular, have proved to be efficient at transducing the cornea and in association with a variety of transgenes, have been used successfully to prolong corneal allograft survival significantly in animal models. The most suitable such vector for future clinical studies in corneal transplantation has yet to be determined, but the most likely include recombinant adenoviral, adeno-associated viral and lentiviral vectors. In this review, we examine the ability of these viral vectors to transduce the cornea, and summarise those studies in which gene therapy has been used to prolong experimental corneal allograft survival.