Potent and nontoxic antisense oligonucleotides containing locked nucleic acids
Potent and nontoxic antisense oligonucleotides containing locked nucleic acids
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DOI：
10.1073/pnas.97.10.5633
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发表时间：
2000-05-09
影响因子：
11.1
通讯作者：
Wengel, J
中科院分区：
文献类型：
--
作者：
Wahlestedt, C;Salmi, P;Wengel, J
Insufficient efficacy and/or specificity of antisense oligonucleotides limit their in vivo usefulness. We demonstrate here that a high-affinity DNA analog, locked nucleic acid (LNA), confers several desired properties to antisense agents. Unlike DNA, LNA/DNA copolymers were not degraded readily in blood serum and cell extracts. However, like DNA, the LNA/DNA copolymers were capable of activating RNase H, an important antisense mechanism of action. In contrast to phosphorothioate-containing oligonucleotides, isosequential LNA analogs did not cause detectable toxic reactions in rat brain. LNA/DNA copolymers exhibited potent antisense activity on assay systems as disparate as a C-protein-coupled receptor in living rat brain and an Escherichia coli reporter gene. LNA-containing oligonucleotides will likely be useful for many antisense applications.
