5-Dihydroxyboryluridine enhances cytosolic penetration of antisense oligonucleotides
Sam Kavoosi1, Kirsten Deprey2, Joshua A Kritzer2
1Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA. kai27@pitt.edu.
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.
More Related Videos
08:46Regioselective O-Glycosylation of Nucleosides via the Temporary 2',3'-Diol Protection by a Boronic Ester for the Synthesis of Disaccharide Nucleosides
Published on: July 26, 2018
08:53Synthesis, Functionalization, and Characterization of Fusogenic Porous Silicon Nanoparticles for Oligonucleotide Delivery
Published on: April 16, 2019
Related Concept Videos
Bioavailability Enhancement: Drug Solubility Enhancement
Bioavailability Enhancement: Drug Permeability Enhancement
Bioavailability Enhancement: Drug Stability Enhancement and GI Retention
Inhibitors of Bacterial DNA Synthesis
Inhibitors of Viral Protein Synthesis
Antiviral Nucleoside Inhibitors
