Targeting Human Osteoarthritic Chondrocytes with Ligand Directed Bacteriophage-Based Particles
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-...
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MDPI AG
2021-11-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/13/12/2343 |
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| author | Aitthiphon Chongchai Sajee Waramit Tunchanok Wongwichai Jirawan Kampangtip Thanyaluck Phitak Prachya Kongtawelert Amin Hajitou Keittisak Suwan Peraphan Pothacharoen |
| author_facet | Aitthiphon Chongchai Sajee Waramit Tunchanok Wongwichai Jirawan Kampangtip Thanyaluck Phitak Prachya Kongtawelert Amin Hajitou Keittisak Suwan Peraphan Pothacharoen |
| author_sort | Aitthiphon Chongchai |
| collection | DOAJ |
| description | 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 (<i>Lucia</i>) 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. |
| first_indexed | 2024-03-10T03:54:55Z |
| format | Article |
| id | doaj.art-3367fdd3285544549306314ae2ed3ec3 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-10T03:54:55Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-3367fdd3285544549306314ae2ed3ec32023-11-23T10:56:37ZengMDPI AGViruses1999-49152021-11-011312234310.3390/v13122343Targeting Human Osteoarthritic Chondrocytes with Ligand Directed Bacteriophage-Based ParticlesAitthiphon Chongchai0Sajee Waramit1Tunchanok Wongwichai2Jirawan Kampangtip3Thanyaluck Phitak4Prachya Kongtawelert5Amin Hajitou6Keittisak Suwan7Peraphan Pothacharoen8Thailand Excellence Centre for Tissue Engineering and Stem Cells, Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, ThailandCancer Phagotherapy Group, Department of Brain Sciences, Burlington Danes Building, Hammersmith Hospital Campus, Imperial College London, London W12 0NN, UKThailand Excellence Centre for Tissue Engineering and Stem Cells, Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, ThailandThailand Excellence Centre for Tissue Engineering and Stem Cells, Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, ThailandThailand Excellence Centre for Tissue Engineering and Stem Cells, Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, ThailandThailand Excellence Centre for Tissue Engineering and Stem Cells, Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, ThailandCancer Phagotherapy Group, Department of Brain Sciences, Burlington Danes Building, Hammersmith Hospital Campus, Imperial College London, London W12 0NN, UKCancer Phagotherapy Group, Department of Brain Sciences, Burlington Danes Building, Hammersmith Hospital Campus, Imperial College London, London W12 0NN, UKThailand Excellence Centre for Tissue Engineering and Stem Cells, Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, ThailandOsteoarthritis (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 (<i>Lucia</i>) 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.https://www.mdpi.com/1999-4915/13/12/2343phage-based particletargeted gene deliverychondrocyte-affinity peptideosteoarthritis |
| spellingShingle | Aitthiphon Chongchai Sajee Waramit Tunchanok Wongwichai Jirawan Kampangtip Thanyaluck Phitak Prachya Kongtawelert Amin Hajitou Keittisak Suwan Peraphan Pothacharoen Targeting Human Osteoarthritic Chondrocytes with Ligand Directed Bacteriophage-Based Particles Viruses phage-based particle targeted gene delivery chondrocyte-affinity peptide osteoarthritis |
| title | Targeting Human Osteoarthritic Chondrocytes with Ligand Directed Bacteriophage-Based Particles |
| title_full | Targeting Human Osteoarthritic Chondrocytes with Ligand Directed Bacteriophage-Based Particles |
| title_fullStr | Targeting Human Osteoarthritic Chondrocytes with Ligand Directed Bacteriophage-Based Particles |
| title_full_unstemmed | Targeting Human Osteoarthritic Chondrocytes with Ligand Directed Bacteriophage-Based Particles |
| title_short | Targeting Human Osteoarthritic Chondrocytes with Ligand Directed Bacteriophage-Based Particles |
| title_sort | targeting human osteoarthritic chondrocytes with ligand directed bacteriophage based particles |
| topic | phage-based particle targeted gene delivery chondrocyte-affinity peptide osteoarthritis |
| url | https://www.mdpi.com/1999-4915/13/12/2343 |
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