选择气溶胶传递系统进行基因传递的基本原理。

Yvonne K Lentz, Thomas J Anchordoquy, Corinne S Lengsfeld
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引用次数: 47

摘要

基因疗法在治疗与肺部有关的疾病方面显示出巨大的希望;然而,目前的输送方法,如喷射和超声雾化降低了这些治疗的活性和有效性。在这些喷雾器中,非复杂质粒DNA表现出极低的转染率,主要归因于剪切诱导降解导致的易位不良和分子完整性丧失。目前研究的重点是通过肺输送途径提高转染率的方法,主要集中在空气流中加入二氧化碳以增加呼吸深度,以及添加阳离子剂将DNA凝聚成紧凑有序的复合物。本研究的目的是研究几种经典的以及最新的雾化装置对非复杂DNA结构的影响。采用静电喷雾、超声波喷雾、振动网喷雾、喷射喷雾等方法对不同大小的质粒和粒状DNA进行处理。根据雾化装置和DNA大小的不同,结果变化很大。这也许可以解释基因治疗在肺部分娩时的低效率。更重要的是,这表明选择雾化装置应考虑DNA的大小,以实现最佳的基因输送到肺部。
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Rationale for the selection of an aerosol delivery system for gene delivery.

Genetic therapeutics show great promise toward the treatment of illnesses associated with the lungs; however, current methods of delivery such as jet and ultrasonic nebulization decrease the activity and effectiveness of these treatments. Extremely low transfection rates exhibited by non-complexed plasmid DNA in these nebulizers have been primarily attributed to poor translocation and loss of molecular integrity as a consequence of shear-induced degradation. Current research focusing on methods to increase transfection rates via the pulmonary delivery route has largely concentrated on the incorporation of carbon dioxide in the air stream to increase breath depth as well as the addition of cationic agents that condense DNA into compact, ordered complexes. The purpose of this study was to examine the impact of several classic as well as the latest atomization devices on the structure of non-complexed DNA. Various sizes of plasmid and cosmid DNA were processed through an electrostatic spray, ultrasonic nebulizer, vibrating mesh nebulizer, and jet nebulizer. Results varied dramatically based upon atomization device as well as DNA size. This may explain the inefficiency experienced by genetic therapeutics during pulmonary delivery. More importantly, this suggests that the selection of an atomization device should consider DNA size in order to achieve optimal gene delivery to the lungs.

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