Targeting human osteoarthritic chondrocytes with ligand directed bacteriophage-based particles
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Author(s)
Type
Journal Article
Abstract
Osteoarthritis (OA) is a degenerative joint disease characterized by progressive deterioration and loss of articular cartilage. There is currently no treatment to reverse the onset of OA. Thus, we developed a targeted delivery strategy to transfer genes into primary human chondrocytes as a proof-of-concept study. We displayed a chondrocyte-affinity peptide (CAP) on the pIII minor coat protein of the M13 filamentous bacteriophage (phage)-based particle carrying a mammalian transgene cassette under cytomegalovirus CMV promoter and inverted terminal repeats (ITRs) cis elements of adeno-associated virus serotype 2 (AAV-2). Primary human articular chondrocytes (HACs) were used as an in vitro model, and the selectivity and binding properties of the CAP ligand in relation to the pathogenic conditions of HACs were characterized. We found that the CAP ligand is highly selective toward pathogenic HACs. Furthermore, the stability, cytotoxicity, and gene delivery efficacy of the CAP-displaying phage (CAP.Phage) were evaluated. We found that the phage particle is stable under a wide range of temperatures and pH values, while showing no cytotoxicity to HACs. Importantly, the CAP.Phage particle, carrying a secreted luciferase (Lucia) reporter gene, efficiently and selectively delivered transgene expression to HACs. In summary, it was found that the CAP ligand preferably binds to pathogenic chondrocytes, and the CAP.Phage particle successfully targets and delivers transgene to HACs.
Date Issued
2021-11-23
Date Acceptance
2021-11-19
Citation
Viruses, 2021, 13 (12)
ISSN
1999-4915
Publisher
MDPI AG
Journal / Book Title
Viruses
Volume
13
Issue
12
Copyright Statement
© 2021 by the authors.
Licensee MDPI, Basel, Switzerland.
This article is an open access article
distributed under the terms and
conditions of the Creative Commons
Attribution (CC BY) license (https://
creativecommons.org/licenses/by/
4.0/).
Licensee MDPI, Basel, Switzerland.
This article is an open access article
distributed under the terms and
conditions of the Creative Commons
Attribution (CC BY) license (https://
creativecommons.org/licenses/by/
4.0/).
License URL
Sponsor
Medical Research Council (MRC)
The Leverhulme Trust
Children with Cancer UK
IP2IPO Innovations Limited
Royal Thai Embassy
Pfizer Limited
Medical Research Council (MRC)
Grant Number
G0701159
DMAID_P22361
2013/147
005988
5302.3/1736
8501338369
MR/T029226/1
Subjects
0605 Microbiology
Publication Status
Published
Article Number
ARTN 2343
Date Publish Online
2021-11-23