当前位置: X-MOL 学术Mol. Pharmaceutics › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Naked pDNA Inhalation Powder Composed of Hyaluronic Acid Exhibits High Gene Expression in the Lungs
Molecular Pharmaceutics ( IF 4.9 ) Pub Date : 2018-08-09 00:00:00 , DOI: 10.1021/acs.molpharmaceut.8b00502
Takaaki Ito 1 , Tomoyuki Okuda 1 , Yoshimasa Takashima 1 , Hirokazu Okamoto 1
Affiliation  

Gene therapy is a breakthrough treatment strategy against several intractable and lethal diseases that previously lacked established treatments. Viral and nonviral vectors have been studied to realize higher gene transfection efficiencies and to suppress the degradation of gene by nucleolytic enzymes in vivo. However, it is often the case that the addition of a vector results in adverse effects. In this study, we identified formulations of dry naked plasmid DNA (pDNA) powders with no vector showing significantly higher gene expression than pDNA solutions including vectors such as polyethylenimine (PEI) in the lungs of mice. We prepared the naked pDNA powders by spray-freeze-drying with various excipients. The gene expression of naked pDNA powders exceeded those of pDNA solutions containing PEI, naked pDNA solution, and reconstituted pDNA powder. Gene expression of each naked pDNA powder was dependent on the composition of excipients. Among them, the mice that were administered the pDNA powder composed of low-molecular-weight hyaluronic acid (LHA) as an excipient showed the highest gene expression. The lactate dehydrogenase activity and concentration of inflammatory cytokines in bronchoalveolar lavage fluid were comparable to those caused by ultrapure water. The results suggest that useful dry naked nucleic acid powders for inhalation could be created by optimizing the excipients, offering new insights into the development of pulmonary gene therapy.

中文翻译:

透明质酸组成的裸露pDNA吸入粉在肺中显示高基因表达

基因疗法是针对几种以前缺乏既定治疗方法的难治性和致死性疾病的突破性治疗策略。已经研究了病毒和非病毒载体以实现更高的基因转染效率并在体内抑制核酸酶对基因的降解。但是,通常情况下,添加载体会产生不利影响。在这项研究中,我们确定了没有载体的干裸质粒DNA(pDNA)粉末配方,其基因表达明显高于pDNA溶液,包括在小鼠肺部中的载体,例如聚乙烯亚胺(PEI)。我们通过与各种赋形剂的喷雾冷冻干燥制备了裸露的pDNA粉末。裸露的pDNA粉末的基因表达超过了含有PEI的pDNA溶液,裸露的pDNA溶液和重组的pDNA粉末的基因表达。每个裸露的pDNA粉末的基因表达取决于赋形剂的组成。其中,被给予由低分子量透明质酸(LHA)构成的pDNA粉末作为赋形剂的小鼠表现出最高的基因表达。乳酸脱氢酶活性和支气管肺泡灌洗液中炎性细胞因子的浓度可与超纯水所致。结果表明,可以通过优化赋形剂来制备有用的干式裸露核酸干粉吸入剂,从而为开发肺基因治疗提供新的见解。给予由低分子量透明质酸(LHA)组成的pDNA粉末作为赋形剂的小鼠显示出最高的基因表达。乳酸脱氢酶活性和支气管肺泡灌洗液中炎性细胞因子的浓度可与超纯水所致。结果表明,可以通过优化赋形剂来制备有用的干式裸露核酸干粉吸入剂,从而为开发肺基因治疗提供新的见识。给予由低分子量透明质酸(LHA)组成的pDNA粉末作为赋形剂的小鼠显示出最高的基因表达。乳酸脱氢酶活性和支气管肺泡灌洗液中炎性细胞因子的浓度可与超纯水所致。结果表明,可以通过优化赋形剂来制备有用的干式裸露核酸干粉吸入剂,从而为开发肺基因治疗提供新的见识。
更新日期:2018-08-09
down
wechat
bug