通过碱基封闭策略实现反义试剂的细胞传递和光化学激活。
Cellular delivery and photochemical activation of antisense agents through a nucleobase caging strategy.
机构信息
North Carolina State University , Department of Chemistry, Raleigh, North Carolina 27695, United States.
出版信息
ACS Chem Biol. 2013 Oct 18;8(10):2272-82. doi: 10.1021/cb400293e. Epub 2013 Aug 19.
Abstract
Antisense oligonucleotides are powerful tools to regulate gene expression in cells and model organisms. However, a transfection or microinjection is typically needed for efficient delivery of the antisense agent. We report the conjugation of multiple HIV TAT peptides to a hairpin-protected antisense agent through a light-cleavable nucleobase caging group. This conjugation allows for the facile delivery of the antisense agent without a transfection reagent, and photochemical activation offers precise control over gene expression. The developed approach is highly modular, as demonstrated by the conjugation of folic acid to the caged antisense agent. This enabled targeted cell delivery through cell-surface folate receptors followed by photochemical triggering of antisense activity. Importantly, the presented strategy delivers native oligonucleotides after light-activation, devoid of any delivery functionalities or modifications that could otherwise impair their antisense activity.
摘要
反义寡核苷酸是调节细胞和模式生物中基因表达的有力工具。然而，通常需要转染或显微注射才能有效地递反抗义试剂。我们报告了通过光可裂解核碱基笼状基团将多个 HIV TAT 肽连接到发夹保护的反义试剂上。这种缀合允许在没有转染试剂的情况下轻松递反抗义试剂，并且光化学激活提供了对基因表达的精确控制。所开发的方法具有高度的模块化，如通过将叶酸连接到被笼状的反义试剂上来证明。这通过细胞表面叶酸受体实现了靶向细胞递送，然后通过光化学触发反义活性。重要的是，所提出的策略在光激活后递送天然寡核苷酸，而不会有任何可能损害其反义活性的递送功能或修饰。
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