AAVrh-10 transduces outer retinal cells in rodents and rabbits following intravitreal administration
Open accessAbstract
Recombinant adeno-associated virus (rAAV) has been widely used for gene delivery in animal models and successfully applied in clinical trials for treating inherited retinal disease. Although subretinal delivery of AAVs can effectively transduce photoreceptors and/or retinal pigmental epithelium (RPE), cells most affected by inherited retinal diseases, the procedure is invasive and complicated, and only delivers the gene to a limited retinal area. AAVs can also be delivered intravitreally to the retina, a much less invasive nonsurgical procedure. However, intravitreal administration of non-modified AAV serotypes tends to transduce only ganglion cells and inner nuclear layer cells. To date, most non-modified AAV serotypes that have been identified are incapable of efficiently transducing photoreceptors and/or RPE when delivered intravitreally. In this study, we investigate the retinal tropism of AAVrh10 vector administered by intravitreal injection to mouse, rat, and rabbit eyes. Our results demonstrate that AAVrh10 is capable of transducing not only inner retinal cells, but also outer retinal cells in all three species, though the transduction efficiency in rabbit was low. In addition, AAVrh10 preferentially transduced outer retinal cells in mouse models of retinal disease. Therefore, AAVrh10 vector could be a useful candidate to intravitreally deliver genes to photoreceptor and RPE cells.
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Intravitreal injection of rAAVrh-10 shifted infection from mainly INL cells towards photoreceptor and RPE cells in Rs1 KO and Rho KO mice (XLRS and RP models, respectively) compared to wild-type mice.
“Intravitreal injection of rAAVrh-10 shifted infection from mainly INL cells towards photoreceptor and RPE cells in Rs1 KO and Rho KO mice (XLRS and RP models, respectively) compared to wild-type mice [310,311].”
From Recombinant Adeno-Associated Viral Vectors (rAAV)-Vector Elements in Ocular Gene Therapy Clinical Trials and Transgene Expression and Bioactivity Assays (2020) · cites this paper as [310]
The Discussion reports that intravitreal AAVrh10 transduction in Rs1-KO and Rho-KO mice was consistently outer-retina dominant, with transduced cells mostly in photoreceptors and RPE. But it describes wild-type transduction as variable—inner-retina dominant, outer-retina dominant, or across all retinal layers—not as mainly in INL cells. The Results section likewise shows several wild-type distribution patterns (page numbers unavailable). (LLM, conf=0.89)
Experimental — accuracy not yet measuredrAAVrh-10 showed promise in transducing the whole rabbit retina and patches of RPE cells, including photoreceptors.
“rAAVrh-10 showed promise in transducing the whole rabbit retina and patches of RPE cells, including photoreceptors [310].”
From Recombinant Adeno-Associated Viral Vectors (rAAV)-Vector Elements in Ocular Gene Therapy Clinical Trials and Transgene Expression and Bioactivity Assays (2020) · cites this paper as [310]
The Results (Rabbit retina; Fundus Images, page not available) report transduced RPE cells and other retinal cell types in rabbits, but describe sparse, regionally distributed fluorescence rather than transduction of the whole rabbit retina. The Discussion (page not available) identifies strong photoreceptor transduction in rats and mice, not rabbits; it describes rabbit RPE transduction as weak. (LLM, conf=0.90)
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Buck, T., & Wijnholds, J. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21124197 · Cited by 92 · see citing works
“Intravitreal injection of rAAVrh-10 shifted infection from mainly INL cells towards photoreceptor and RPE cells in Rs1KO and RhoKO mice (XLRS and RP models, respectively) compared to wild-type mice [310,311].”
BackgroundResultNovel AAV44.9-Based Vectors Display Exceptional Characteristics for Retinal Gene Therapy
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- Authors
- Zeng, Y., Qian, H., Wu, Z., Marangoni, D., Sieving, P. A., & Bush, R. A.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Bush, Ronald A.
- Venue
- Gene Therapy
- Published
- 2019-07-15
- Volume
- 26
- Issue
- 9
- Pages
- 386-398
- ISSN
- 0969-7128 (ISSN-L)
- 1476-5462
- PMC
- PMC11388630
- OpenAlex
- W2962397111
- Cited by
- 12
- References
- 55
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 1 · 2023: 1 · 2022: 1 · 2021: 1 · 2020: 5
- FWCI
- 1.05
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Gene Therapy (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- ArTS Archivio della ricerca di Trieste (University of Trieste https://www.units.it/) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institutes of Health (Z99 EY999999)
- National Institute on Deafness and Other Communication Disorders
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Keywords
- AAVrh10, recombinant adeno-associated virus, intravitreal gene delivery, photoreceptors, retinal pigment epithelium, inherited retinal disease, transduction efficiency, species differences, mice, rats, rabbits
- MeSH terms
- Dependovirus, Animals, Cytomegalovirus, Genetic Vectors, Male, Photoreceptor Cells, Rabbits, Retina, Retinal Diseases, Transduction, Genetic, Rats, Sprague-Dawley, Green Fluorescent Proteins, Mice, Rats, Viral Tropism, Intravitreal Injections
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