ADAMTS5-specific gapmer release from an albumin biomolecular assembly and cartilage internalization triggered by ultrasound
Loading...
Access rights
openAccess
CC BY
CC BY
publishedVersion
URL
Journal Title
Journal ISSN
Volume Title
A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä
This publication is imported from Aalto University research portal.
View publication in the Research portal (opens in new window)
View/Open full text file from the Research portal (opens in new window)
Other link related to publication (opens in new window)
View publication in the Research portal (opens in new window)
View/Open full text file from the Research portal (opens in new window)
Other link related to publication (opens in new window)
Unless otherwise stated, all rights belong to the author. You may download, display and print this publication for Your own personal use. Commercial use is prohibited.
Date
Major/Subject
Mcode
Degree programme
Language
en
Pages
10
Series
Drug Delivery, Volume 32, issue 1, pp. 1-10
Abstract
Objective: Antisense oligonucleotides (ASOs) have reached the clinic; however, they lack tissue specificity. Albumin is a plasma-abundant macromolecule that has been shown to accumulate in inflamed tissues. In this work, we have designed a recombinant human albumin (rHA)-based biomolecular assembly incorporating a DNase-resistant phosphorothioate-based complementary oligonucleotide (cODN) and an anti-ADAMTS5 ASO for potential delivery to inflamed sites. Ultrasound (US) was used to trigger ASO release from the assembly and enhance internalization into articular cartilage. Methods: A phosphorothioate cODN was conjugated to rHA through a maleimide cross-linker after which, a therapeutic ADAMTS5-specific gapmer ASO was annealed to the cODN. ASO release was assessed after exposing the biomolecular assembly to different US conditions using an US-actuated medical needle operating at 32.2 kHz. Gene silencing efficiency of US-treated anti-ADAMTS5 ASO was assessed in human primary chondrocytes isolated from osteoarthritic patients. US-mediated ASO penetration into articular cartilage was assessed on ex vivo bovine articular cartilage. Results: ASO release was observed after exposure to US waves in continuous mode conditions that did not compromise ASO gene silencing efficiency in human chondrocytes. Furthermore, US increased ASO internalization into bovine articular cartilage after 30 min of application without detrimental effects on chondrocyte viability. Conclusion: A medical needle driven by continuous US waves at 32.2 kHz has the capability of disassembling a duplex oligonucleotide and enhancing released ASOs internalization into articular cartilage. This work offers the potential delivery and the local triggered release of ASOs at the surface of articular cartilage providing potential benefits for the treatment of diverse cartilage pathologies.Description
Publisher Copyright: © 2025 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. | openaire: EC/H2020/55335/EU//CARTHAGO
Keywords
Other note
Citation
Elkhashab, M, Barreto, G, Fauconnier, M, Le Bourlout, Y, Creemers, L B, Nieminen, H J & Howard, K A 2025, 'ADAMTS5-specific gapmer release from an albumin biomolecular assembly and cartilage internalization triggered by ultrasound', Drug Delivery, vol. 32, no. 1, 2464921, pp. 1-10. https://doi.org/10.1080/10717544.2025.2464921