Evidence map›Paper›PMID 39967271›Full record

ArticleDrug delivery2025

ADAMTS5-specific gapmer release from an albumin biomolecular assembly and cartilage internalization triggered by ultrasound.

Marwa Elkhashab, Goncalo Barreto, Maxime Fauconnier, Yohann Le Bourlout, Laura B Creemers, Heikki J Nieminen, Kenneth A Howard

Abstract read
In one paragraph

Article in Drug delivery, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

7 authors.

Marwa ElkhashabInterdisciplinary Nanoscience Center (iNANO) and Department of Molecular Biology, Aarhus University, Aarhus C, Denmark.
Goncalo BarretoMedical Ultrasonics Laboratory (MEDUSA), Department of Neuroscience and Biomedical Engineering, Aalto University, Espoo, Finland.
Maxime FauconnierMedical Ultrasonics Laboratory (MEDUSA), Department of Neuroscience and Biomedical Engineering, Aalto University, Espoo, Finland.
Yohann Le BourloutMedical Ultrasonics Laboratory (MEDUSA), Department of Neuroscience and Biomedical Engineering, Aalto University, Espoo, Finland.
Laura B CreemersDepartment of Orthopedics, University Medical Center Utrecht, Utrecht, The Netherlands.
Heikki J NieminenMedical Ultrasonics Laboratory (MEDUSA), Department of Neuroscience and Biomedical Engineering, Aalto University, Espoo, Finland.
Kenneth A HowardInterdisciplinary Nanoscience Center (iNANO) and Department of Molecular Biology, Aarhus University, Aarhus C, Denmark.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveAntisense 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.

methodsA 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

resultsASO 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.

conclusionA 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.

Indexed as

ADAMTS5 ProteinCartilage, ArticularOligonucleotides, AntisenseAnimalsCattleCells, CulturedChondrocytesGene SilencingHumansOsteoarthritisUltrasonic WavesADAMTS5 ProteinADAMTS5 protein, humanOligonucleotides, AntisenseAlbuminAntisensebiomolecular assemblycartilageultrasound

Identifiers

PMID39967271
PMCPMC11841101

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.