Structure of DNA-cationic liposome complexes: DNA intercalation in multilamellar membranes in distinct interhelical packing regimes
Structure of DNA-cationic liposome complexes: DNA intercalation in multilamellar membranes in distinct interhelical packing regimes
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DOI：
10.1126/science.275.5301.810
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发表时间：
1997-02-07
期刊：
影响因子：
56.9
通讯作者：
Safinya, CR
中科院分区：
文献类型：
--
作者：
Radler, JO;Koltover, I;Safinya, CR
阳离子脂质体与DNA复合物（CL-DNA）是一种很有前途的基于合成的非病毒DNA载体，用于基因治疗。用同步辐射X射线衍射和光学显微镜研究了CL-DNA复合物在亚纳米到微米尺度上的溶液结构。添加线性噬菌体或质粒DNA的CL导致了一个意想不到的拓扑结构的转变，从脂质体光学双折射液晶凝聚小球。X射线衍射的小球揭示了一种新的多层结构与交替的脂质双层和DNA单层。DNA链形成一维晶格，具有不同的螺旋间包装制度。值得注意的是，在等电点制度中，脂质稀释后，DNA轴间距在24.5和57.1埃之间扩展，并且指示可能通过链波动增强的长距离静电诱导的排斥。
Cationic liposomes complexed with DNA (CL-DNA) are promising synthetically based nonviral carriers of DNA vectors for gene therapy. The solution structure of CL-DNA complexes was probed on length scales from subnanometer to micrometer by synchrotron x-ray diffraction and optical microscopy. The addition of either linear lambda-phage or plasmid DNA to CLs resulted in an unexpected topological transition from liposomes to optically birefringent liquid-crystalline condensed globules. X-ray diffraction of the globules revealed a novel multilamellar structure with alternating lipid bilayer and DNA monolayers. The lambda-DNA chains form a one-dimensional lattice with distinct interhelical packing regimes. Remarkably, in the isoelectric point regime, the lambda-DNA interaxial spacing expands between 24.5 and 57.1 angstroms upon lipid dilution and is indicative of a long-range electrostatic-induced repulsion that is possibly enhanced by chain undulations.