Mashhour B
INSERM U 380, ICGM, Paris.
Bull Acad Natl Med. 1996 Mar;180(3):645-57.
Replication-deficient adenoviral vectors have been used to transfer foreign DNA into a variety of cells including post-mitotic cells, in vivo. They constitute the obligatory targets of gene transfer for a number of ocular diseases that have been elucidated at the molecular level and are potential targets for gene therapy. We have therefore analysed the ability of an adenoviral vector to transfer in vivo the E. coli LacZ gene into ocular cells of mice and rabbits. Injection of up to 3 10(7) pfu in mice and 10(9) pfu in rabbits, into the vitreous cavity, the anterior chamber or the peribulbar space did not result in any detectable cytopathic effect and was associated with endocytosis of viral particles in corneal endothelial, photoreceptor, bipolar, ganglionic and oculomotor muscle cells, depending on the administration route. At the viral titer used (3 10(7) or 10(9) pfu), the expression was detected for at least 50 days. These results open new prospects for the treatment of some retinal hereditary disorders and acquired corneal or retinal alterations due to inflammatory disease.
复制缺陷型腺病毒载体已被用于在体内将外源DNA导入包括有丝分裂后细胞在内的多种细胞。对于一些已在分子水平上阐明的眼部疾病，它们构成了基因转移的必要靶点，并且是基因治疗的潜在靶点。因此，我们分析了一种腺病毒载体在体内将大肠杆菌LacZ基因导入小鼠和兔子眼部细胞的能力。向小鼠玻璃体腔、前房或球周间隙注射高达3×10⁷ 个空斑形成单位（pfu），向兔子注射10⁹ pfu，均未产生任何可检测到的细胞病变效应，并且根据给药途径，病毒颗粒会被角膜内皮细胞、光感受器细胞、双极细胞、神经节细胞和动眼肌细胞内吞。在所使用的病毒滴度（3×10⁷ 或10⁹ pfu）下，至少50天可检测到表达。这些结果为治疗某些视网膜遗传性疾病以及因炎症性疾病导致的后天性角膜或视网膜病变开辟了新的前景。
