Plasmid electrotransfer of eye ciliary muscle: principles and therapeutic efficacy using hTNF-α soluble receptor in uveitis
Plasmid electrotransfer of eye ciliary muscle: principles and therapeutic efficacy using hTNF-α soluble receptor in uveitis
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DOI：
10.1096/fj.05-4737fje
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发表时间：
2006-02-01
期刊：
影响因子：
4.8
通讯作者：
Behar-Cohen, F.
中科院分区：
文献类型：
--
作者：
Bloquel, C.;Bejjani, R.;Behar-Cohen, F.
由于其小尺寸和特殊的隔离屏障，眼睛是局部治疗的理想目标。重组蛋白眼部递送需要侵入性和疼痛的重复注射。或者，转染的组织可以用作转基因编码的治疗性蛋白的局部生产者。我们开发了一种靶向睫状肌的非损伤性电介导质粒递送技术（电转移），该技术用作治疗性蛋白质长期表达和分泌的储库组织。观察到报告基因的高表达和持久表达，仅限于睫状肌。嵌合TNF-α可溶性受体（hTNFR-Is）电转移导致内毒素诱导的葡萄膜炎大鼠房水中蛋白质分泌增加，并显著抑制临床和组织学炎症评分。在血清中未检测到hTNFR-Is，证明使用该方法局部递送蛋白质。如本研究中所进行的，质粒电转移至睫状肌未诱导任何眼部病理学或结构损伤。通过睫状肌电转移的局部和持续的治疗性蛋白质生产是一种有前途的替代大量炎症性、退行性或血管生成性疾病的重复眼内蛋白质给药。
Due to its small size and particular isolating barriers, the eye is an ideal target for local therapy. Recombinant protein ocular delivery requires invasive and painful repeated injections. Alternatively, a transfected tissue might be used as a local producer of transgene‐encoded therapeutic protein. We have developed a nondamaging electrically mediated plasmid delivery technique (electrotransfer) targeted to the ciliary muscle, which is used as a reservoir tissue for the long‐lasting expression and secretion of therapeutic proteins. High and long‐lasting reporter gene expression was observed, which was restricted to the ciliary muscle. Chimeric TNF‐α soluble receptor (hTNFR‐Is) electrotransfer led to elevated protein secretion in aqueous humor and to drastic inhibition of clinical and histological inflammation scores in rats with endotoxininduced uveitis. No hTNFR‐Is was detected in the serum, demonstrating the local delivery of proteins using this method. Plasmid electrotransfer to the ciliary muscle, as performed in this study, did not induce any ocular pathology or structural damage. Local and sustained therapeutic protein production through ciliary muscle electrotransfer is a promising alternative to repeated intraocular protein administration for a large number of inflammatory, degenerative, or angiogenic diseases.