Issue 56, 2023

5-Dihydroxyboryluridine enhances cytosolic penetration of antisense oligonucleotides

Abstract

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.

Graphical abstract: 5-Dihydroxyboryluridine enhances cytosolic penetration of antisense oligonucleotides

Supplementary files

Article information

Article type
Communication
Submitted
20 Apr 2023
Accepted
30 May 2023
First published
22 Jun 2023

Chem. Commun., 2023,59, 8692-8695

Author version available

5-Dihydroxyboryluridine enhances cytosolic penetration of antisense oligonucleotides

S. Kavoosi, K. Deprey, J. A. Kritzer and K. Islam, Chem. Commun., 2023, 59, 8692 DOI: 10.1039/D3CC01945D

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