Multitasking by multivalent circular DNA aptamers

被引:27
作者
Di Giusto, DA [1 ]
Knox, SM
Lai, YC
Tyrelle, GD
Aung, MT
King, GC
机构
[1] Univ New S Wales, Sch Biotechnol & Biomol Sci, Sydney, NSW 2052, Australia
[2] Univ Minnesota, Dept Genet Cell Biol & Dev, Minneapolis, MN 55455 USA
[3] Natl Yang Ming Univ, Inst Bioinformat, Taipei 11221, Taiwan
关键词
DNA structures; immobilization; nanostructures; nucleic acids; therapeutic targeting;
D O I
10.1002/cbic.200500316
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Nucleic acid aptamers ore finding increasing applications in biology, especially as therapeutic candidates and diagnostic components. An important characteristic in meeting the needs of these applications is improved stability in physiological fluids, which is most often accomplished with chemical modification or unnatural nucleotides. In an alternative approach we hove specified the design of a multivalent circular DNA aptamer topology that encompasses a number of properties relevant to nucleic acid therapeutic candidates, especially the ability to multitask by combining different activities together within a modular structure. Improved stability in blood products, greater conformational stability, antidoting by complementary circular antiaptamers, heterovalency, transcription factor decoy activity and minimal unintended effects upon the cellular innate immune response are desirable properties that are described here. Multitasking by circular DNA aptamers could similarly find applications in diagnostics and biomaterials, where the combination of interchangeable modules might generate new functions, such as anticoagulation coupled with reversible cell capture as, described here. These results provide a platform for further exploration of multivalent circular aptamer properties, especially in novel combinations of nucleic acid therapeutic modes.
引用
收藏
页码:535 / 544
页数:10
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