Journal article
Assessment of Adeno-Associated Virus Serotype Tropism in Human Retinal Explants
Human gene therapy, Vol.29(4), pp.424-436
04/01/2018
DOI: 10.1089/hum.2017.179
PMCID: PMC5909113
PMID: 29160116
Abstract
Advances in the discovery of the causes of monogenic retinal disorders, combined with technologies for the delivery of DNA to the retina, offer enormous opportunities for the treatment of previously untreatable blinding diseases. However, for gene augmentation to be most effective, vectors that have the correct cell-type specificity are needed. While animal models are very useful, they often exhibit differences in retinal cell surface receptors compared to the human retina. This study evaluated the use of an ex vivo organotypic explant system to test the transduction efficiency and tropism of seven different adeno-associated virus type 2 (AAV2) serotypes in the human retina and retinal pigment epithelium-choroid—AAV2/1, AAV2/2, AAV2/4, AAV2/5, AAV2/6, AAV2/8, and AAV2/9—all driving expression of GFP under control of the cytomegalovirus promoter. After 7 days in culture, it was found that AAV2/4 and AAV2/5 were particularly efficient at transducing photoreceptor cells and that AAV2/5 was highly specific to the outer nuclear layer, whereas AAV2/8 displayed consistently low transduction of photoreceptors. To validate the authenticity of the organotypic culture system, the transduction of the same set of AAVs was also compared in a pig model, in which sub-retinal injections in vivo were compared to cultured and transduced organotypic cultures ex vivo . This study shows how different AAV serotypes behave in the human retina and provides insight for further investigation of each of these serotypes for gene augmentation–based treatment of inherited retinal degeneration.
Details
- Title: Subtitle
- Assessment of Adeno-Associated Virus Serotype Tropism in Human Retinal Explants
- Creators
- Luke A Wiley - University of IowaErin R Burnight - University of IowaEmily E Kaalberg - University of IowaChunhua Jiao - University of IowaMegan J Riker - University of IowaJennifer A Halder - University of IowaMeagan A Luse - University of IowaIan C Han - University of IowaStephen R Russell - University of IowaElliott H Sohn - University of IowaEdwin M Stone - University of IowaBudd A Tucker - University of IowaRobert F Mullins - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Human gene therapy, Vol.29(4), pp.424-436
- DOI
- 10.1089/hum.2017.179
- PMID
- 29160116
- PMCID
- PMC5909113
- NLM abbreviation
- Hum Gene Ther
- ISSN
- 1043-0342
- eISSN
- 1557-7422
- Publisher
- Mary Ann Liebert, Inc
- Language
- English
- Date published
- 04/01/2018
- Academic Unit
- Iowa Neuroscience Institute; Ophthalmology and Visual Sciences
- Record Identifier
- 9983979977602771
Metrics
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