Program in Gene Therapy, Department of Pediatrics, Carver College of Medicine, The University of Iowa, Iowa City, IA 52242, USA.
Gene Ther. 2009 Sep;16(9):1059-65. doi: 10.1038/gt.2009.87. Epub 2009 Jul 30.
Pulmonary gene therapy may ultimately cure diseases such as cystic fibrosis, alpha1-antitrypsin deficiency, lung cancer and pulmonary hypertension. Efficient expression of delivered genes in target cell types is essential for the achievement of this goal. To this end, re-administration of viral vectors may be required (1) to increase the percentage of transduced airway epithelial cells, (2) to direct gene transfer to individual lobes during successive delivery sessions or (3) to boost attenuated expression over time. Immune responses to viral proteins or viral-encoded proteins are the greatest barrier to repeated vector administration.
肺基因治疗最终可能治愈囊性纤维化、α1-抗胰蛋白酶缺乏症、肺癌和肺动脉高压等疾病。为实现这一目标，将递送到靶细胞类型的基因高效表达是至关重要的。为此，可能需要重新给予病毒载体（1）增加转导的气道上皮细胞的百分比，（2）在连续的递药过程中指导基因转移到各个肺叶，或（3）随时间增强减弱的表达。对病毒蛋白或病毒编码蛋白的免疫反应是重复给予载体的最大障碍。
