IRUS Total

Targeting human osteoarthritic chondrocytes with ligand directed bacteriophage-based particles

File Description SizeFormat 
Manuscript_ Viruses 2021.pdfPublished version4.86 MBAdobe PDFView/Open
Title: Targeting human osteoarthritic chondrocytes with ligand directed bacteriophage-based particles
Authors: Chongchai, A
Waramit, S
Wongwichai, T
Kampangtip, J
Phitak, T
Kongtawelert, P
Hajitou, A
Suwan, K
Pothacharoen, P
Item 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.
Issue Date: 23-Nov-2021
Date of Acceptance: 19-Nov-2021
URI: http://hdl.handle.net/10044/1/93104
DOI: 10.3390/v13122343
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/).
Sponsor/Funder: Medical Research Council (MRC)
The Leverhulme Trust
Children with Cancer UK
IP2IPO Innovations Limited
Royal Thai Embassy
Pfizer Limited
Medical Research Council (MRC)
Funder's Grant Number: G0701159
Keywords: 0605 Microbiology
Publication Status: Published
Article Number: ARTN 2343
Appears in Collections:Faculty of Medicine
Department of Brain Sciences

This item is licensed under a Creative Commons License Creative Commons