Pre-retinal delivery of recombinant adeno-associated virus vector significantly improves retinal transduction efficiency
Intravitreal injection is the most widely used injection technique for ocular gene delivery. However, vector diffusion is attenuated by physical barriers and neutralizing antibodies in the vitreous. The 13-lined ground squirrel (13-LGS), as in humans, has a larger relative vitreous body volume than...
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| Format: | Article |
| Language: | English |
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Elsevier
2021-09-01
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| Series: | Molecular Therapy: Methods & Clinical Development |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2329050121001078 |
| _version_ | 1818366067498549248 |
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| author | Hanmeng Zhang Benjamin S. Sajdak Dana K. Merriman Joseph Carroll Daniel M. Lipinski |
| author_facet | Hanmeng Zhang Benjamin S. Sajdak Dana K. Merriman Joseph Carroll Daniel M. Lipinski |
| author_sort | Hanmeng Zhang |
| collection | DOAJ |
| description | Intravitreal injection is the most widely used injection technique for ocular gene delivery. However, vector diffusion is attenuated by physical barriers and neutralizing antibodies in the vitreous. The 13-lined ground squirrel (13-LGS), as in humans, has a larger relative vitreous body volume than the more common rodent models such as rats and mice, which would further reduce transduction efficiency with the intravitreal injection route. We report here a “pre-retinal” injection approach that leads to detachment of the posterior hyaloid membrane and delivers vector into the space between vitreous and inner retina. Vectors carrying a ubiquitously expressing mCherry reporter were injected into the deep vitreous or pre-retinal space in adult wild-type 13-LGSs. Then, adeno-associated virus (AAV)-mediated mCherry expression was evaluated with non-invasive imaging, immunofluorescence, and flow cytometry. Compared to deep vitreous delivery, pre-retinal administration achieved pan-retinal gene expression with a lower vector dose volume and significantly increased the number of transduced cone photoreceptors. These results suggest that pre-retinal injection is a promising tool in the development of gene therapy strategies in animal models and is a potential approach for use in human research, particularly in younger individuals with an intact posterior hyaloid membrane and stable vitreous. |
| first_indexed | 2024-12-13T22:30:16Z |
| format | Article |
| id | doaj.art-ecba9c07b0ea45f8bbc1717cdbabf4bc |
| institution | Directory Open Access Journal |
| issn | 2329-0501 |
| language | English |
| last_indexed | 2024-12-13T22:30:16Z |
| publishDate | 2021-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Methods & Clinical Development |
| spelling | doaj.art-ecba9c07b0ea45f8bbc1717cdbabf4bc2022-12-21T23:29:06ZengElsevierMolecular Therapy: Methods & Clinical Development2329-05012021-09-012296106Pre-retinal delivery of recombinant adeno-associated virus vector significantly improves retinal transduction efficiencyHanmeng Zhang0Benjamin S. Sajdak1Dana K. Merriman2Joseph Carroll3Daniel M. Lipinski4Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI 53226, USA; Department of Ophthalmology and Visual Sciences, Medical College of Wisconsin, 925 N 87th Street, Milwaukee, WI 53226, USACell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI 53226, USA; Department of Ophthalmology and Visual Sciences, Medical College of Wisconsin, 925 N 87th Street, Milwaukee, WI 53226, USA; Morgridge Institute for Research, Madison, WI 53715, USADepartment of Biology, University of Wisconsin Oshkosh, Oshkosh, WI 54901, USACell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI 53226, USA; Department of Ophthalmology and Visual Sciences, Medical College of Wisconsin, 925 N 87th Street, Milwaukee, WI 53226, USACell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI 53226, USA; Department of Ophthalmology and Visual Sciences, Medical College of Wisconsin, 925 N 87th Street, Milwaukee, WI 53226, USA; Nuffield Laboratory of Ophthalmology, University of Oxford, Oxford OX1 2JD, UK; Corresponding author: Daniel M. Lipinski, Department of Ophthalmology and Visual Sciences, Medical College of Wisconsin, 925 N 87th Street, Milwaukee, WI 53226, USA.Intravitreal injection is the most widely used injection technique for ocular gene delivery. However, vector diffusion is attenuated by physical barriers and neutralizing antibodies in the vitreous. The 13-lined ground squirrel (13-LGS), as in humans, has a larger relative vitreous body volume than the more common rodent models such as rats and mice, which would further reduce transduction efficiency with the intravitreal injection route. We report here a “pre-retinal” injection approach that leads to detachment of the posterior hyaloid membrane and delivers vector into the space between vitreous and inner retina. Vectors carrying a ubiquitously expressing mCherry reporter were injected into the deep vitreous or pre-retinal space in adult wild-type 13-LGSs. Then, adeno-associated virus (AAV)-mediated mCherry expression was evaluated with non-invasive imaging, immunofluorescence, and flow cytometry. Compared to deep vitreous delivery, pre-retinal administration achieved pan-retinal gene expression with a lower vector dose volume and significantly increased the number of transduced cone photoreceptors. These results suggest that pre-retinal injection is a promising tool in the development of gene therapy strategies in animal models and is a potential approach for use in human research, particularly in younger individuals with an intact posterior hyaloid membrane and stable vitreous.http://www.sciencedirect.com/science/article/pii/S2329050121001078retinagene therapyAAVposterior hyaloid membranepre-retinalintravitreal |
| spellingShingle | Hanmeng Zhang Benjamin S. Sajdak Dana K. Merriman Joseph Carroll Daniel M. Lipinski Pre-retinal delivery of recombinant adeno-associated virus vector significantly improves retinal transduction efficiency Molecular Therapy: Methods & Clinical Development retina gene therapy AAV posterior hyaloid membrane pre-retinal intravitreal |
| title | Pre-retinal delivery of recombinant adeno-associated virus vector significantly improves retinal transduction efficiency |
| title_full | Pre-retinal delivery of recombinant adeno-associated virus vector significantly improves retinal transduction efficiency |
| title_fullStr | Pre-retinal delivery of recombinant adeno-associated virus vector significantly improves retinal transduction efficiency |
| title_full_unstemmed | Pre-retinal delivery of recombinant adeno-associated virus vector significantly improves retinal transduction efficiency |
| title_short | Pre-retinal delivery of recombinant adeno-associated virus vector significantly improves retinal transduction efficiency |
| title_sort | pre retinal delivery of recombinant adeno associated virus vector significantly improves retinal transduction efficiency |
| topic | retina gene therapy AAV posterior hyaloid membrane pre-retinal intravitreal |
| url | http://www.sciencedirect.com/science/article/pii/S2329050121001078 |
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