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DNA-阳离子脂质体复合物的结构:在不同的螺旋间堆积模式下,DNA嵌入多层膜中。

Structure of DNA-cationic liposome complexes: DNA intercalation in multilamellar membranes in distinct interhelical packing regimes.

作者信息

Rädler J O, Koltover I, Salditt T, Safinya C R

机构信息

Materials Department, University of California, Santa Barbara, CA 93106, USA.

出版信息

Science. 1997 Feb 7;275(5301):810-4. doi: 10.1126/science.275.5301.810.

DOI:10.1126/science.275.5301.810
PMID:9012343
Abstract

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.

摘要

与DNA复合的阳离子脂质体(CL-DNA)是用于基因治疗的基于合成的很有前景的非病毒DNA载体。通过同步加速器X射线衍射和光学显微镜在从亚纳米到微米的长度尺度上探测了CL-DNA复合物的溶液结构。向阳离子脂质体中添加线性λ噬菌体或质粒DNA会导致从脂质体到光学双折射液晶凝聚球的意外拓扑转变。球状体的X射线衍射揭示了一种具有交替脂质双层和DNA单层的新型多层结构。λ-DNA链形成具有不同螺旋间堆积方式的一维晶格。值得注意的是,在等电点状态下,脂质稀释时λ-DNA的轴间距在24.5至57.1埃之间扩大,这表明可能由链波动增强的长程静电诱导排斥作用。

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