Efficient non-viral ocular gene transfer with compacted DNA nanoparticles.
Efficient non-viral ocular gene transfer with compacted DNA nanoparticles.
复制标题
用压实的DNA纳米颗粒有效的非病毒眼基因转移。
DOI：
10.1371/journal.pone.0000038
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发表时间：
2006-12-20
期刊：
影响因子：
3.7
通讯作者：
Naash, Muna I.
中科院分区：
文献类型：
--
作者：
Farjo, Rafal;Skaggs, Jeff;Quiambao, Alexander B.;Cooper, Mark J.;Naash, Muna I.
眼睛是基因治疗的绝佳候选者，因为它具有免疫特权，而且许多致病基因已经被很好地理解了。为了实现这一目标，我们评估了压缩DNA纳米颗粒作为非病毒基因转移到眼部组织的系统的效率。在一项人体临床试验中，研究的压缩DNA纳米颗粒已被证明是安全有效的，对质粒大小没有理论上的限制，不会引起免疫反应，并且可以高度浓缩。在这里，我们表明这些纳米颗粒可以通过改变注射部位来靶向眼睛内的不同组织。几乎所有类型的眼睛细胞都能被纳米颗粒转染，并产生剂量依赖性的基因表达水平。最令人印象深刻的是，这些纳米颗粒的视网膜下递送几乎转染了所有的光感受器群体，并产生了几乎与视网膜中表达最高的基因视杆蛋白相同的表达水平。由于没有观察到对视网膜功能的有害影响，这种治疗策略在临床上似乎是可行的，并且提供了一种高效的非病毒技术，可以安全地在视网膜和其他眼部组织中传递和表达核酸。
The eye is an excellent candidate for gene therapy as it is immune privileged and much of the disease-causing genetics are well understood. Towards this goal, we evaluated the efficiency of compacted DNA nanoparticles as a system for non-viral gene transfer to ocular tissues. The compacted DNA nanoparticles examined here have been shown to be safe and effective in a human clinical trial, have no theoretical limitation on plasmid size, do not provoke immune responses, and can be highly concentrated. Here we show that these nanoparticles can be targeted to different tissues within the eye by varying the site of injection. Almost all cell types of the eye were capable of transfection by the nanoparticle and produced robust levels of gene expression that were dose-dependent. Most impressively, subretinal delivery of these nanoparticles transfected nearly all of the photoreceptor population and produced expression levels almost equal to that of rod opsin, the highest expressed gene in the retina. As no deleterious effects on retinal function were observed, this treatment strategy appears to be clinically viable and provides a highly efficient non-viral technology to safely deliver and express nucleic acids in the retina and other ocular tissues.
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影响因子：
4.4
作者：
Chen, Y;Moiseyev, Q;Ma, JX
通讯作者：
Ma, JX
影响因子：
5.1
作者：
Chen, ZY;He, CY;Kay, MA
通讯作者：
Kay, MA
影响因子：
56.9
作者：
Edwards, AO;Ritter, R;Farrer, LA
通讯作者：
Farrer, LA
DOI：
10.1073/pnas.94.13.6916
发表时间：
1997-06-24
影响因子：
11.1
作者：
Flannery, JG;Zolotukhin, S;Hauswirth, WW
通讯作者：
Hauswirth, WW
影响因子：
3.9
作者：
Jun, AS;Larkin, DFP
通讯作者：
Larkin, DFP