Evaluation of AAV-DJ vector for retinal gene therapy
Purpose The most common virus vector used in gene therapy research for ophthalmologic diseases is the adeno-associated virus (AAV) vector, which has been used successfully in a number of preclinical and clinical studies. It is important to evaluate novel AAV vectors in animal models for application...
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| Format: | Article |
| Language: | English |
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PeerJ Inc.
2019-01-01
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| Series: | PeerJ |
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| Online Access: | https://peerj.com/articles/6317.pdf |
| _version_ | 1797420269957021696 |
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| author | Yusaku Katada Kenta Kobayashi Kazuo Tsubota Toshihide Kurihara |
| author_facet | Yusaku Katada Kenta Kobayashi Kazuo Tsubota Toshihide Kurihara |
| author_sort | Yusaku Katada |
| collection | DOAJ |
| description | Purpose The most common virus vector used in gene therapy research for ophthalmologic diseases is the adeno-associated virus (AAV) vector, which has been used successfully in a number of preclinical and clinical studies. It is important to evaluate novel AAV vectors in animal models for application of clinical gene therapy. The AAV-DJ (type 2/type 8/type 9 chimera) was engineered from shuffling eight different wild-type native viruses. In this study, we investigated the efficiency of gene transfer by AAV-DJ injections into the retina. Methods One microliter of AAV-2-CAGGS-EGFP or AAV-DJ-CAGGS-EGFP vector at a titer of 1.4 × 10e12 vg/ml was injected intravitreally or subretinally in each eye of C57BL/6 mice. We evaluated the transduction characteristics of AAV-2 and -DJ vectors using fluorescence microscopy and electroretinography. Results The results confirmed that AAV-DJ could deeply transfer gene to photoreceptor layer with intravitreal injection and has an efficient gene transfer to various cell types especially the Mueller cells in the retina. Retinal function was not affected by AAV-DJ infection or ectopic EGFP expression. Conclusions The AAV-DJ vector efficiently induces the reporter gene in both the inner and outer murine retina without functional toxicity. These data indicated that the AAV-DJ vector is a useful tool for the gene therapy research targeting retinal disorders. |
| first_indexed | 2024-03-09T06:59:11Z |
| format | Article |
| id | doaj.art-7c997c3b46614719934429293e5f8445 |
| institution | Directory Open Access Journal |
| issn | 2167-8359 |
| language | English |
| last_indexed | 2024-03-09T06:59:11Z |
| publishDate | 2019-01-01 |
| publisher | PeerJ Inc. |
| record_format | Article |
| series | PeerJ |
| spelling | doaj.art-7c997c3b46614719934429293e5f84452023-12-03T09:55:59ZengPeerJ Inc.PeerJ2167-83592019-01-017e631710.7717/peerj.6317Evaluation of AAV-DJ vector for retinal gene therapyYusaku Katada0Kenta Kobayashi1Kazuo Tsubota2Toshihide Kurihara3Department of Ophthalmology, School of Medicine, Keio University, Shinjuku-ku, Tokyo, JapanSection of Viral Vector Development, Center for Genetic Analysis of Behavior, National Institute for Physiological Sciences, National Institutes of Natural Sciences, Okazaki, Aichi, JapanDepartment of Ophthalmology, School of Medicine, Keio University, Shinjuku-ku, Tokyo, JapanDepartment of Ophthalmology, School of Medicine, Keio University, Shinjuku-ku, Tokyo, JapanPurpose The most common virus vector used in gene therapy research for ophthalmologic diseases is the adeno-associated virus (AAV) vector, which has been used successfully in a number of preclinical and clinical studies. It is important to evaluate novel AAV vectors in animal models for application of clinical gene therapy. The AAV-DJ (type 2/type 8/type 9 chimera) was engineered from shuffling eight different wild-type native viruses. In this study, we investigated the efficiency of gene transfer by AAV-DJ injections into the retina. Methods One microliter of AAV-2-CAGGS-EGFP or AAV-DJ-CAGGS-EGFP vector at a titer of 1.4 × 10e12 vg/ml was injected intravitreally or subretinally in each eye of C57BL/6 mice. We evaluated the transduction characteristics of AAV-2 and -DJ vectors using fluorescence microscopy and electroretinography. Results The results confirmed that AAV-DJ could deeply transfer gene to photoreceptor layer with intravitreal injection and has an efficient gene transfer to various cell types especially the Mueller cells in the retina. Retinal function was not affected by AAV-DJ infection or ectopic EGFP expression. Conclusions The AAV-DJ vector efficiently induces the reporter gene in both the inner and outer murine retina without functional toxicity. These data indicated that the AAV-DJ vector is a useful tool for the gene therapy research targeting retinal disorders.https://peerj.com/articles/6317.pdfAdeno-associated viral vectorGene therapyRetina |
| spellingShingle | Yusaku Katada Kenta Kobayashi Kazuo Tsubota Toshihide Kurihara Evaluation of AAV-DJ vector for retinal gene therapy PeerJ Adeno-associated viral vector Gene therapy Retina |
| title | Evaluation of AAV-DJ vector for retinal gene therapy |
| title_full | Evaluation of AAV-DJ vector for retinal gene therapy |
| title_fullStr | Evaluation of AAV-DJ vector for retinal gene therapy |
| title_full_unstemmed | Evaluation of AAV-DJ vector for retinal gene therapy |
| title_short | Evaluation of AAV-DJ vector for retinal gene therapy |
| title_sort | evaluation of aav dj vector for retinal gene therapy |
| topic | Adeno-associated viral vector Gene therapy Retina |
| url | https://peerj.com/articles/6317.pdf |
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