A1 Refereed original research article in a scientific journal
Synthesis of Site-Specific Antibody-[60]Fullerene-Oligonucleotide Conjugates for Cellular Targeting
Authors: Äärelä Antti, Räsänen Kati, Holm Patrik, Salo Harri, Virta Pasi
Publisher: AMER CHEMICAL SOC
Publication year: 2023
Journal: ACS Applied Bio Materials
Journal name in source: ACS APPLIED BIO MATERIALS
Journal acronym: ACS APPL BIO MATER
Volume: 6
Issue: 8
First page : 3189
Last page: 3198
Number of pages: 10
ISSN: 2576-6422
eISSN: 2576-6422
DOI: https://doi.org/10.1021/acsabm.3c00318
Web address : https://doi.org/10.1021/acsabm.3c00318
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/180411556
An ideal therapeutic antibody-oligonucleotideconjugate(AOC) would be a uniform construct, contain a maximal oligonucleotide(ON) payload, and retain the antibody (Ab)-mediated binding properties,which leads to an efficient delivery of the ON cargo to the site oftherapeutic action. Herein, [60]fullerene-based molecular sphericalnucleic acids (MSNAs) have been site-specifically conjugated to antibodies(Abs), and the Ab-mediated cellular targeting of the MSNA-Abconjugates has been studied. A well-established glycan engineeringtechnology and robust orthogonal click chemistries yielded the desireduniform MSNA-Ab conjugates (MW & SIM; 270 kDa), with an oligonucleotide(ON):Ab ratio of 24:1, in 20-26% isolated yields. These AOCsretained the antigen binding properties (Trastuzumab's bindingto human epidermal growth factor receptor 2, HER2), studied by biolayerinterferometry. In addition, Ab-mediated endocytosis was demonstratedwith live-cell fluorescence and phase-contrast microscopy on BT-474breast carcinoma cells, overexpressing HER2. The effect on cell proliferationwas analyzed by label-free live-cell time-lapse imaging.
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