AAV-mediated, in vivo gene delivery to the rotator cuff
Tendon injuries present a considerable clinical challenge due to the limited regenerative capacity of tendons. The use of gene transfer to deliver growth factors to sites of tendon damage has been suggested as a promising strategy for improving tendon regeneration. A major issue for this approach is...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
AO Research Institute Davos
2023-12-01
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| Series: | European Cells & Materials |
| Subjects: | |
| Online Access: | https://www.ecmjournal.org/papers/vol046/vol046a08.php |
| _version_ | 1797232791918739456 |
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| author | RE Sherwin EB McGlinch MA Barry CM Lopez De Padilla DR Montonye CH Evans A Atasoy-Zeybek |
| author_facet | RE Sherwin EB McGlinch MA Barry CM Lopez De Padilla DR Montonye CH Evans A Atasoy-Zeybek |
| author_sort | RE Sherwin |
| collection | DOAJ |
| description | Tendon injuries present a considerable clinical challenge due to the limited regenerative capacity of tendons. The use of gene transfer to deliver growth factors to sites of tendon damage has been suggested as a promising strategy for improving tendon regeneration. A major issue for this approach is to identify clinically acceptable vectors that can deliver genes to the cells of the tendon, preferably by in vivo delivery. Adeno-associated virus (AAV) has many advantages in this regard, including a favourable safety profile and the ability to sustain long-term transgene expression. Here we explored the use of AAV to deliver marker genes to the supra- and infra-spinatus tendons of the rotator cuff in the rat by injection into the subacromial space. First, we screened various AAV serotypes for their transducing ability towards rat and human tenocytes in vitro. Of the 10 serotypes tested, AAV2.5 and AAV2 exhibited the highest in vitro transduction efficiency in both rat and human tenocytes. Ex vivo transduction of cells within explants of isolated, intact tendon was also demonstrated. Injection of AAV2.5 encoding luciferase into the subacromial space confirmed gene delivery to the infra-, but not supra-, spinatus tendon in vivo with transgene expression persisting for 7 days post-transduction. These data demonstrate the ability of AAV2.5 to deliver genes to the infraspinatus tendon, leading to sustained local expression following in vivo delivery. Our findings suggest that AAV2.5 has several advantages as vector for stimulating tendon regeneration by local, in vivo, gene transfer. |
| first_indexed | 2024-04-24T16:05:54Z |
| format | Article |
| id | doaj.art-1c335fb313b241aa9680ba862c6f47c9 |
| institution | Directory Open Access Journal |
| issn | 1473-2262 |
| language | English |
| last_indexed | 2024-04-24T16:05:54Z |
| publishDate | 2023-12-01 |
| publisher | AO Research Institute Davos |
| record_format | Article |
| series | European Cells & Materials |
| spelling | doaj.art-1c335fb313b241aa9680ba862c6f47c92024-04-01T02:54:12ZengAO Research Institute DavosEuropean Cells & Materials1473-22622023-12-014615417010.22203/eCM.v046a08AAV-mediated, in vivo gene delivery to the rotator cuffRE Sherwin0EB McGlinch1MA Barry2CM Lopez De Padilla3DR Montonye4CH Evans5A Atasoy-Zeybek6RE SherwinEB McGlinchMA BarryCM Lopez De PadillaDR MontonyeCH EvansA Atasoy-ZeybekTendon injuries present a considerable clinical challenge due to the limited regenerative capacity of tendons. The use of gene transfer to deliver growth factors to sites of tendon damage has been suggested as a promising strategy for improving tendon regeneration. A major issue for this approach is to identify clinically acceptable vectors that can deliver genes to the cells of the tendon, preferably by in vivo delivery. Adeno-associated virus (AAV) has many advantages in this regard, including a favourable safety profile and the ability to sustain long-term transgene expression. Here we explored the use of AAV to deliver marker genes to the supra- and infra-spinatus tendons of the rotator cuff in the rat by injection into the subacromial space. First, we screened various AAV serotypes for their transducing ability towards rat and human tenocytes in vitro. Of the 10 serotypes tested, AAV2.5 and AAV2 exhibited the highest in vitro transduction efficiency in both rat and human tenocytes. Ex vivo transduction of cells within explants of isolated, intact tendon was also demonstrated. Injection of AAV2.5 encoding luciferase into the subacromial space confirmed gene delivery to the infra-, but not supra-, spinatus tendon in vivo with transgene expression persisting for 7 days post-transduction. These data demonstrate the ability of AAV2.5 to deliver genes to the infraspinatus tendon, leading to sustained local expression following in vivo delivery. Our findings suggest that AAV2.5 has several advantages as vector for stimulating tendon regeneration by local, in vivo, gene transfer.https://www.ecmjournal.org/papers/vol046/vol046a08.phptendon healingsupraspinatus tendoninfraspinatus tendonrotator cufftenocytesadeno-associated virusadeno-associated virus 2.5gene therapy for tendon healing |
| spellingShingle | RE Sherwin EB McGlinch MA Barry CM Lopez De Padilla DR Montonye CH Evans A Atasoy-Zeybek AAV-mediated, in vivo gene delivery to the rotator cuff European Cells & Materials tendon healing supraspinatus tendon infraspinatus tendon rotator cuff tenocytes adeno-associated virus adeno-associated virus 2.5 gene therapy for tendon healing |
| title | AAV-mediated, in vivo gene delivery to the rotator cuff |
| title_full | AAV-mediated, in vivo gene delivery to the rotator cuff |
| title_fullStr | AAV-mediated, in vivo gene delivery to the rotator cuff |
| title_full_unstemmed | AAV-mediated, in vivo gene delivery to the rotator cuff |
| title_short | AAV-mediated, in vivo gene delivery to the rotator cuff |
| title_sort | aav mediated in vivo gene delivery to the rotator cuff |
| topic | tendon healing supraspinatus tendon infraspinatus tendon rotator cuff tenocytes adeno-associated virus adeno-associated virus 2.5 gene therapy for tendon healing |
| url | https://www.ecmjournal.org/papers/vol046/vol046a08.php |
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