Pfeifer Corinna, Himmel Anne, Geiger Johannes-Peter, Aneja Manish K, Rudolph Carsten
Division of Molecular Pulmonology, Department of Pediatrics, Ludwig-Maximilians University, Lindwurmstrasse 2A, 80337 Munich, Germany.
Ther Deliv. 2010 Jul;1(1):133-48. doi: 10.4155/tde.10.11.
Many inherited and acquired pulmonary disorders without satisfactory therapies may be amenable to gene therapy. Despite numerous advances, efficient delivery and expression of the therapeutic transgene at physiological levels for phenotypic correction of disease has proved elusive. This article focuses on various strategies aimed at achieving targeted delivery to the lungs. Both physical methods and biological targeting have been successfully applied in various gene delivery systems. Targeting of different cell types has been achieved by pseudotyping of viral vectors with capsids from different serotypes and modification of nonviral vectors with targeting ligands. Both classes of vectors are discussed with respect to their gene delivery and expression efficiencies, longevity of expression and immunogenicity. Moreover, gene therapy clinical trials for different lung diseases are discussed.
许多没有令人满意治疗方法的遗传性和获得性肺部疾病可能适合基因治疗。尽管取得了众多进展，但要在生理水平上高效递送和表达治疗性转基因以实现疾病表型纠正仍难以做到。本文重点关注旨在实现肺部靶向递送的各种策略。物理方法和生物靶向已成功应用于各种基因递送系统。通过用来自不同血清型的衣壳对病毒载体进行假型化以及用靶向配体修饰非病毒载体，已实现对不同细胞类型的靶向。将针对这两类载体的基因递送和表达效率、表达持续时间和免疫原性进行讨论。此外，还将讨论针对不同肺部疾病的基因治疗临床试验。
