Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Present Address, Creyon Bio, Inc., San Diego, CA 92121, USA.
Chembiochem. 2022 Nov 4;23(21):e202200374. doi: 10.1002/cbic.202200374. Epub 2022 Oct 6.
Caged morpholino oligonucleotides (cMOs) are synthetic tools that allow light-inducible gene silencing in live organisms. Previously reported cMOs have utilized hairpin, duplex, and cyclic structures, as well as caged nucleobases. While these antisense technologies enable efficient optical control of RNA splicing and translation, they can have limited dynamic range. A new caging strategy was developed where the two MO termini are conjugated to an internal position through a self-immolative trifunctional linker, thereby generating a bicyclic cMO that is conformationally resistant to RNA binding. The efficacy of this alternative cMO design has been demonstrated in zebrafish embryos and compared to linear MOs and monocyclic constructs.
笼状修饰的吗啉代寡核苷酸 (cMOs) 是一种可将基因在活生物体中进行光诱导沉默的合成工具。先前报道的 cMOs 利用了发夹、双链和环状结构以及笼状碱基。虽然这些反义技术能够实现 RNA 剪接和翻译的有效光学控制，但它们的动态范围可能有限。开发了一种新的笼状策略，其中两个 MO 末端通过自毁三功能接头连接到内部位置，从而生成构象上抵抗 RNA 结合的双环 cMO。这种替代 cMO 设计的功效已在斑马鱼胚胎中得到证实，并与线性 MO 和单环构建体进行了比较。
