Barriers to inhaled gene therapy of obstructive lung diseases: A review.
Barriers to inhaled gene therapy of obstructive lung diseases: A review.
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DOI：
10.1016/j.jconrel.2016.05.031
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发表时间：
2016-10-28
期刊：
影响因子：
--
通讯作者：
Suk JS
中科院分区：
文献类型：
--
作者：
Kim N;Duncan GA;Hanes J;Suk JS
阻塞性肺病的遗传起源的知识使得吸入基因疗法成为当前仅限于管理疾病症状的护理标准的有吸引力的替代方案。最初的肺基因治疗临床试验发生在20世纪90年代初，随后发现了导致囊性纤维化（CF）的遗传缺陷，这是一种单基因疾病。然而，尽管经过二十多年的努力，基因治疗尚未帮助CF或任何其他阻塞性肺病患者。进展缓慢的部分原因是对吸入基因治疗的生物学障碍缺乏了解。令人鼓舞的是，临床试验表明，患者对各种病毒载体和非病毒基因载体的吸入基因治疗耐受良好，持续的研究提供了宝贵的经验和资源，可能会导致这种治疗策略的未来成功。在这篇综述中，我们首先介绍了具有代表性的阻塞性肺疾病，并探讨目前可用的治疗方案的局限性。然后，我们回顾成功执行吸入基因治疗的关键组成部分，包括基因递送系统，主要生理障碍和克服它们的策略，以及临床前疾病模型的进展，最有前途的系统可能被确定用于人体临床试验。
Knowledge of genetic origins of obstructive lung diseases has made inhaled gene therapy an attractive alternative to the current standards of care that are limited to managing disease symptoms. Initial lung gene therapy clinical trials occurred in the early 1990s following the discovery of the genetic defect responsible for cystic fibrosis (CF), a monogenic disorder. However, despite over two decades of intensive effort, gene therapy has yet to help patients with CF or any other obstructive lung disease. The slow progress is due in part to poor understanding of the biological barriers to inhaled gene therapy. Encouragingly, clinical trials have shown that inhaled gene therapy with various viral vectors and non-viral gene vectors is well tolerated by patients, and continued research has provided valuable lessons and resources that may lead to future success of this therapeutic strategy. In this review, we first introduce representative obstructive lung diseases and examine limitations of currently available therapeutic options. We then review key components for successful execution of inhaled gene therapy, including gene delivery systems, primary physiological barriers and strategies to overcome them, and advances in preclinical disease models with which the most promising systems may be identified for human clinical trials.
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DOI：
10.1016/j.jcf.2004.05.010
发表时间：
2004-08-01
期刊：
Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society
影响因子：
--
作者：
Bals, Robert;Beisswenger, Christoph;Chinet, Thierry
通讯作者：
Chinet, Thierry
影响因子：
3.5
作者：
Boeckle, S;von Gersdorff, K;Ogris, M
通讯作者：
Ogris, M
影响因子：
11.1
作者：
Boucher, R. C.
通讯作者：
Boucher, R. C.
影响因子：
168.9
作者：
Alton, EWFW;Stern, M;Geddes, DM
通讯作者：
Geddes, DM
影响因子：
3.8
作者：
Anderson, Donald S.;Patchin, Esther S.;Van Winkle, Laura S.
通讯作者：
Van Winkle, Laura S.