Stabilization of cationic liposome-plasmid DNA complexes by polyamines and poly(ethylene glycol)-phospholipid conjugates for efficient in vivo gene delivery
Stabilization of cationic liposome-plasmid DNA complexes by polyamines and poly(ethylene glycol)-phospholipid conjugates for efficient in vivo gene delivery
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DOI：
10.1016/s0014-5793(96)01397-x
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发表时间：
1997-01-03
期刊：
影响因子：
3.5
通讯作者：
Papahadjopoulos, D
中科院分区：
文献类型：
--
作者：
Hong, KL;Zheng, WW;Papahadjopoulos, D
通过(1)加入少量聚乙二醇-磷脂缀合物或(2)在形成脂质体-质粒复合物之前用多胺凝聚DNA，制备阳离子脂质体与质粒DNA的稳定复合物，这些制剂在4℃下稳定数月，并且在小鼠体内静脉注射后具有可重复的高转染活性。在这些条件下，标记基因（荧光素酶）的表达主要在肺中（达到每毫克组织蛋白3 ng的表达值），但也在其他组织中较少表达。非稳定制剂在4天内失去了所有转染活性。在这些配方中，胆固醇，而不是二油基磷脂酰乙醇胺，是有效维持体内高转染活性的辅助脂质。这些配方技术的新发展将增强脂质体介导基因治疗的潜力。
Stable complexes of cationic liposomes with plasmid DNA were prepared by (1) including a small amount of poly(ethylene glycol)-phospholipid conjugate or (2) condensing the DNA with polyamines prior to the formation of liposome-plasmid complexes, These preparations were stable for months at 4 degrees C and gave reproducible high transfection activity for in vivo gene delivery after intravenous injection in mice. Under these conditions, the expression of marker gene (luciferase) was primarily in the lungs (reaching values up to 3 ng expression per mg tissue protein), but also in other tissues to a lesser extent. Non-stabilized formulations lost all their transfection activity in 4 days. In these formulations cholesterol, not dioleoylphosphatidylethanolamine, was the helper lipid effective for sustaining high transfection activity in vivo. These new developments in formulation technology should enhance the potential for liposome-mediated gene therapy.