5-Dihydroxyboryluridine enhances cytosolic penetration of antisense oligonucleotides.
5-Dihydroxyboryluridine enhances cytosolic penetration of antisense oligonucleotides.
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5-二羟基硼酰脲增强反义寡核苷酸的胞质渗透。
DOI：
10.1039/d3cc01945d
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Islam,Kabirul
中科院分区：
文献类型：
--
作者：
Kavoosi,Sam;Deprey,Kirsten;Kritzer,JoshuaA;Islam,Kabirul
核酸药物开发的最大挑战是它们的跨细胞膜递送。在此，我们利用硼酸和细胞表面聚糖之间的可逆结合来帮助合成寡核苷酸的细胞递送。我们安装的人工核苷酸5-二羟基boryluridine（5 boU）中的一个位点特异性的方式在druglike反义寡核苷酸，并证明这些含硼酸酯的核酸具有增强的胞质渗透和剪接校正活性相比，非硼酸酯类似物。5 boU的策略性掺入是增强治疗性核酸的细胞递送的简单、模块化和潜在的通用手段。
The most significant challenge for nucleic acid drug development is their delivery across the cell membrane. Herein, we harness the reversible binding between boronic acids and cell surface glycans to aid in the cellular delivery of synthetic oligonucleotides. We install the artificial nucleotide 5-dihydroxyboryluridine (5boU) in a site-specific manner within druglike antisense oligonucleotides and demonstrate that these boronate-containing nucleic acids have enhanced cytosolic penetration and splice-correcting activity compared to non-boronate analogs. Strategic incorporation of 5boU is a simple, modular, and potentially general means of enhancing cellular delivery of therapeutic nucleic acids.