Kim Tae Woo, Chung Hesson, Kwon Ick Chan, Sung Ha Chin, Shin Byung Chul, Jeong Seo Young
Graduate School of Medicine, Korea University, 1, 5-ka, Anam-dong, Sungbuk-ku, Seoul 136-791, Korea.
J Gene Med. 2005 Jun;7(6):749-58. doi: 10.1002/jgm.711.
Delivery of genes to airway mucosa would be a very valuable method for gene therapy and vaccination. However, there have been few reports on suitable gene delivery systems for administration. In this study, we use a cationic emulsion system, which is physically stable and facilitates the transfer of genes in the presence of up to 90% serum, as a mucosal gene carrier.
Cationic lipid emulsion was formulated with squalene and 1,2-dioleoyl-sn-glycero-3-trimethylammoniumpropane (DOTAP) as major components. Emulsions formed stable complexes with DNA and protected and transferred DNA to target cells against DNase I digestion in the presence of mucosal destabilizers such as heparin sulfate (a polysaccharide of the glycosaminoglycan family in mucosa) and Newfectan (a natural lung extract of bovine) in an in vitro system. In contrast, commercial liposomes and counter liposomes, made with an identical lipid composition of emulsions, failed. After in vivo intranasal instillation, the cationic emulsion showed at least 200 times better transfection activity than the liposomal carriers in both nasal tissue and lung.
These findings show that cationic emulsions can mediate gene transfection into airway epithelium, making it a good choice for transferring therapeutic genes and for genetic vaccination against an pathogenic infection via an airway route.
将基因递送至气道黏膜对于基因治疗和疫苗接种而言是一种非常有价值的方法。然而，关于合适的基因递送给药系统的报道却很少。在本研究中，我们使用一种阳离子乳液系统作为黏膜基因载体，该系统物理性质稳定，在高达90%血清存在的情况下也能促进基因转移。
阳离子脂质乳液由角鲨烯和1,2 - 二油酰基 - sn - 甘油 - 3 - 三甲基氯化铵（DOTAP）作为主要成分配制而成。乳液与DNA形成稳定的复合物，并在体外系统中，在诸如硫酸肝素（黏膜中糖胺聚糖家族的一种多糖）和Newfectan（牛的天然肺提取物）等黏膜去稳定剂存在的情况下，保护DNA并将其转移至靶细胞，使其免受DNase I消化。相比之下，由与乳液相同脂质组成制成的市售脂质体和反脂质体则未能成功。经鼻内滴注至体内后，阳离子乳液在鼻组织和肺中的转染活性比脂质体载体至少高200倍。
这些发现表明阳离子乳液能够介导基因转染至气道上皮，使其成为通过气道途径递送治疗性基因以及针对病原体感染进行基因疫苗接种的良好选择。
