Ríos C D, Ooboshi H, Piegors D, Davidson B L, Heistad D D
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242, USA.
Arterioscler Thromb Vasc Biol. 1995 Dec;15(12):2241-5. doi: 10.1161/01.atv.15.12.2241.
Previous studies of gene transfer to blood vessels in vivo have relied on intraluminal, catheter-based methods for delivery of adenoviral and other vectors. In this study, topical application of a replication-deficient adenoviral vector was used as an alternative method of gene transfer to the vessel wall. We administered recombinant adenovirus (1.0 x 1.5 x 10(10) pfu/mL) containing the nuclear targeted bacterial beta-galactosidase gene topically to arteries in normal and atherosclerotic cynomolgus monkeys. Topical administration was achieved by injection of adenoviral suspension within the periarterial sheath. Segments of femoral and carotid arteries were examined histochemically after staining with 5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside 1 day after treatment with the adenovirus. After topical administration of virus, beta-galactosidase activity was observed in approximately 20% of cells in the adventitia in both normal and atherosclerotic arteries. There was no detectable beta-galactosidase activity in cells of the intima or media. Thus, topical application provides an alternative method for gene transfer to blood vessels in vivo. This approach, which does not require interruption of blood flow and does not disrupt the endothelium, may be useful for studies of vascular biology and perhaps gene therapy in both normal and atherosclerotic vessels.
以往在体内将基因导入血管的研究依赖于基于导管的腔内方法来递送腺病毒和其他载体。在本研究中，使用复制缺陷型腺病毒载体局部应用作为将基因导入血管壁的另一种方法。我们将含有核靶向细菌β-半乳糖苷酶基因的重组腺病毒（1.0×1.5×10¹⁰ pfu/mL）局部应用于正常和动脉粥样硬化食蟹猴的动脉。通过在动脉周围鞘内注射腺病毒悬液实现局部给药。在用腺病毒治疗1天后，用5-溴-4-氯-3-吲哚基-β-D-吡喃半乳糖苷染色后，对股动脉和颈动脉节段进行组织化学检查。局部应用病毒后，在正常和动脉粥样硬化动脉的外膜中约20%的细胞中观察到β-半乳糖苷酶活性。在内膜或中膜的细胞中未检测到β-半乳糖苷酶活性。因此，局部应用为体内将基因导入血管提供了另一种方法。这种方法不需要中断血流且不破坏内皮，可能对血管生物学研究以及正常和动脉粥样硬化血管的基因治疗都有用。
