Preclinical dose-escalation study of intravitreal AAV-RS1 gene therapy in a mouse model of X-linked retinoschisis: dose-dependent expression and improved retinal structure and function
Open accessAbstract
Gene therapy for inherited retinal diseases has been shown to ameliorate functional and structural defects in both animal models and in human clinical trials. X-linked retinoschisis (XLRS) is an early-age onset macular dystrophy resulting from loss of an extracellular matrix protein (RS1). In preparation for a human clinical gene therapy trial, we conducted a dose-range efficacy study of the clinical vector, a self-complementary AAV delivering a human retinoschisin (RS1) gene under control of the RS1 promoter and an interphotoreceptor binding protein enhancer (AAV8-scRS/IRBPhRS), in the retinoschisin knockout (Rs1-KO) mouse. The therapeutic vector at 1 × 10(6) to 2.5 × 10(9) (1E6-2.5E9) vector genomes (vg)/eye or vehicle was administered to one eye of 229 male Rs1-KO mice by intravitreal injection at 22 ± 3 days postnatal age (PN). Analysis of retinal function (dark-adapted electroretinogram, ERG), structure (cavities and outer nuclear layer thickness) by in vivo retinal imaging using optical coherence tomography, and retinal immunohistochemistry (IHC) for RS1 was done 3-4 months and/or 6-9 months postinjection (PI). RS1 IHC staining was dose dependent across doses ≥1E7 vg/eye, and the threshold for significant improvement in all measures of retinal structure and function was 1E8 vg/eye. Higher doses, however, did not produce additional improvement. At all doses showing efficacy, RS1 staining in Rs1-KO mouse was less than that in wild-type mice. Improvement in the ERG and RS1 staining was unchanged or greater at 6-9 months than at 3-4 months PI. This study demonstrates that vitreal administration of AAV8 scRS/IRBPhRS produces significant improvement in retinal structure and function in the mouse model of XLRS over a vector dose range that can be extended to a human trial. It indicates that a fully normal level of RS1 expression is not necessary for a therapeutic effect.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
AAV-mediated RS1 expression in the Rs1-knockout mouse improved retinal structure, with fewer cavities, and function, as measured by electroretinogram.
“AAV-mediated augmentation of human RS1 expression in the Rs1-knockout mouse led to improved retinal structure (reduced retinal cavities) and function (electroretinogram response)”
From Correcting visual loss by genetics and prosthetics (2020) · cites this paper as Bush 2016
Early results from a phase I human trial of RS1 gene therapy showed possible closure of parafoveal schisis cavities in at least one patient.
“while early results from a phase I human trial has demonstrated potential closure of parafoveal schisis cavities in at least one patient [Bush 2016, Cukras 2018].”
From Correcting visual loss by genetics and prosthetics (2020) · cites this paper as Bush 2016
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Effect of gene therapy on visual function in Leber’s congenital amaurosis
Bainbridge, J. W. B., Smith, A. J., Barker, S. S., Robbie, S., Henderson, R., Balaggan, K., Viswanathan, A., Holder, G. E., Stockman, A., Tyler, N., et al. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa0802268 · Cited by 1,924 · see citing works
Motulsky, H. J., & Brown, R. E. (2006) · BMC Bioinformatics · doi:10.1186/1471-2105-7-123 · Cited by 1,616 · see citing works
The Major Cell Populations of the Mouse Retina
Jeon, C.-J., Strettoi, E., & Masland, R. H. (1998) · The Journal of Neuroscience · doi:10.1523/jneurosci.18-21-08936.1998 · Cited by 1,429 · see citing works
ISCEV Standard for full-field clinical electroretinography (2008 update)
Marmor, M. F., Fulton, A. B., Holder, G. E., Miyake, Y., Brigell, M., & Bach, M. (2008) · Documenta Ophthalmologica · doi:10.1007/s10633-008-9155-4 · Cited by 1,004 · see citing works
Maguire, A. M., High, K. A., Auricchio, A., Wright, J. F., Pierce, E. A., Testa, F., Mingozzi, F., Bennicelli, J. L., Ying, G.-S., Rossi, S., et al. (2009) · The Lancet · doi:10.1016/s0140-6736(09)61836-5 · Cited by 865 · see citing works
Cideciyan, A. V., Alemán, T. S., Boye, S. L., Schwartz, S., Kaushal, S., Román, A. J., Pang, J., Sumaroka, A., Windsor, E. A. M., Wilson, J. M., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0807027105 · Cited by 674 · see citing works
Positional cloning of the gene associated with X-linked juvenile retinoschisis
Sauer, C. G., Gehrig, A., Warneke-Wittstock, R., Marquardt, A., Ewing, C. C., Gibson, A., Lorenz, B., Jurklies, B., & Weber, B. H. F. (1997) · Nature Genetics · doi:10.1038/ng1097-164 · Cited by 497 · see citing works
A schematic eye for the mouse, and comparisons with the rat
Remtulla, S., & Hallett, P. E. (1985) · Vision Research · doi:10.1016/0042-6989(85)90076-8 · Cited by 387 · see citing works
Sensing extracellular matrix: An update on discoidin domain receptor function
Vogel, W. F., Abdulhussein, R., & Ford, C. E. (2006) · Cellular Signalling · doi:10.1016/j.cellsig.2006.02.012 · Cited by 368 · see citing works
X-linked juvenile retinoschisis: Clinical diagnosis, genetic analysis, and molecular mechanisms
Molday, R. S., Kellner, U., & Weber, B. H. F. (2012) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2011.12.002 · Cited by 334 · see citing works
Cideciyan, A. V., Hauswirth, W. W., Aleman, T. S., Kaushal, S., Schwartz, S. B., Boye, S. L., Windsor, E. A. M., Conlon, T. J., Sumaroka, A., Pang, J.-J., et al. (2009) · Human Gene Therapy · doi:10.1089/hum.2009.086 · Cited by 312 · see citing works
Bennicelli, J., Wright, J. F., Komaromy, A., Jacobs, J. B., Hauck, B., Zelenaia, O., Mingozzi, F., Hui, D., Chung, D., Rex, T. S., et al. (2008) · Molecular Therapy · doi:10.1038/sj.mt.6300389 · Cited by 267 · see citing works
Dosage thresholds for AAV2 and AAV8 photoreceptor gene therapy in monkey
Vandenberghe, L. H., Bell, P., Maguire, A. M., Cearley, C. N., Xiao, R., Calcedo, R., Wang, L., Castle, M. J., Maguire, A. C., Grant, R., et al. (2011) · Science Translational Medicine · doi:10.1126/scitranslmed.3002103 · Cited by 242 · see citing works
Expression of X-linked retinoschisis protein RS1 in photoreceptor and bipolar cells
Molday, L. L., Hicks, D., Sauer, C. G., Weber, B. H. F., & Molday, R. S. (2001) · PubMed · doi:10.5283/epub.35825 · Cited by 200 · see citing works
Vision 1 Year after Gene Therapy for Leber's Congenital Amaurosis
Cideciyan, A. V., Hauswirth, W. W., Alemán, T. S., Kaushal, S., Schwartz, S., Boye, S. L., Windsor, E. A. M., Conlon, T. J., Sumaroka, A., Román, A. J., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmc0903652 · Cited by 199 · see citing works
Zeng, Y., Takada, Y., Kjellström, S., Hiriyanna, K. T., Tanikawa, A., Wawrousek, E. F., Smaoui, N., Caruso, R. C., Bush, R. A., & Sieving, P. A. (2004) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.04-0576 · Cited by 191 · see citing works
Self-citationMin, S.-H., Molday, L. L., Seeliger, M. W., Dinculescu, A., Timmers, A. M., Janßen, A., Tonagel, F., Tanimoto, N., Weber, B. H. F., Molday, R. S., et al. (2005) · Molecular Therapy · doi:10.1016/j.ymthe.2005.06.002 · Cited by 174 · see citing works
OUTER RETINAL TUBULATION IN ADVANCED AGE-RELATED MACULAR DEGENERATION
Schaal, K. B., Freund, K. B., Litts, K. M., Zhang, Y., Messinger, J. D., & Curcio, C. A. (2015) · Retina · doi:10.1097/iae.0000000000000471 · Cited by 151 · see citing works
The Status ofRPE65Gene Therapy Trials: Safety and EfficacyPreprint
Pierce, E. A., & Bennett, J. (2015) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a017285 · Cited by 151 · see citing works
Grayson, C. (2000) · Human Molecular Genetics · doi:10.1093/hmg/9.12.1873 · Cited by 148 · see citing works
Permeability and Diffusion in Vitreous Humor: Implications for Drug Delivery
Xu, J., Heys, J. J., Barocas, V. H., & Randolph, T. W. (2000) · Pharmaceutical Research · doi:10.1023/a:1007517912927 · Cited by 147 · see citing works
Park, T. K., Wu, Z., Kjellström, S., Zeng, Y., Bush, R. A., Sieving, P. A., & Colosi, P. (2009) · Gene Therapy · doi:10.1038/gt.2009.61 · Cited by 145 · see citing works
Self-citationKjellström, S., Bush, R. A., Zeng, Y., Takada, Y., & Sieving, P. A. (2007) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.07-0203 · Cited by 126 · see citing works
Self-citationSynaptic pathology and therapeutic repair in adult retinoschisis mouse by AAV-RS1 transfer
Ou, J., Vijayasarathy, C., Ziccardi, L., Chen, S., Zeng, Y., Marangoni, D., Pope, J. G., Bush, R. A., Wu, Z., Li, W., et al. (2015) · Journal of Clinical Investigation · doi:10.1172/jci81380 · Cited by 114 · see citing works
Self-citationTakada, Y., Fariss, R. N., Tanikawa, A., Zeng, Y., Carper, D. A., Bush, R. A., & Sieving, P. A. (2004) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.04-0156 · Cited by 113 · see citing works
Self-citationMowat, F. M., Gornik, K. R., Dinculescu, A., Boye, S. L., Hauswirth, W. W., Petersen-Jones, S. M., & Bartoe, J. T. (2014) · Gene Therapy · doi:10.1038/gt.2013.64 · Cited by 108 · see citing works
Takada, Y., Vijayasarathy, C., Zeng, Y., Kjellström, S., Bush, R. A., & Sieving, P. A. (2008) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.07-1071 · Cited by 100 · see citing works
Self-citationCONGENITAL X-LINKED RETINOSCHISIS CLASSIFICATION SYSTEM
Prenner, J. L., Capone, A., Ciaccia, S., Takada, Y., Sieving, P. A., & Trese, M. T. (2006) · Retina · doi:10.1097/01.iae.0000244290.09499.c1 · Cited by 98 · see citing works
Self-citationRetinoschisin gene therapy in photoreceptors, Müller glia or all retinal cells in the Rs1h−/− mouse
Byrne, L. C., Öztürk, B. E., Lee, T., Fortuny, C., Visel, M., Dalkara, D., Schaffer, D. V., & Flannery, J. G. (2014) · Gene Therapy · doi:10.1038/gt.2014.31 · Cited by 96 · see citing works
Janßen, A., Min, S.-H., Molday, L. L., Tanimoto, N., Seeliger, M. W., Hauswirth, W. W., Molday, R. S., & Weber, B. H. F. (2008) · Molecular Therapy · doi:10.1038/mt.2008.57 · Cited by 95 · see citing works
Robson, J. G., & Frishman, L. J. (1996) · Journal of the Optical Society of America A · doi:10.1364/josaa.13.000613 · Cited by 95 · see citing works
Retinal Photoreceptor Count, Retinal Surface Area, and Optic Disc Size in Normal Human Eyes
Panda‐Jonas, S., Jonas, J. B., Jakobczyk-Zmija, M. J., & Schneider, U. (1994) · Ophthalmology · doi:10.1016/s0161-6420(94)31305-4 · Cited by 93 · see citing works
Gerth‐Kahlert, C. (2008) · Archives of Ophthalmology · doi:10.1001/archopht.126.6.807 · Cited by 76 · see citing works
The mouse X-linked juvenile retinoschisis cDNA: expression in photoreceptors.
Reid, S. N., Akhmedov, N. B., Piriev, N. I., Kozak, C., Danciger, M., & Farber, D. B. (1999) · Gene · doi:10.1016/s0378-1119(98)00578-2 · Cited by 76 · see citing works
Bowles, K. E., Cukras, C. A., Turriff, A. E., Sergeev, Y. V., Vitale, S., Bush, R. A., & Sieving, P. A. (2011) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.11-8115 · Cited by 65 · see citing works
Self-citationVijayasarathy, C., Sui, R., Zeng, Y., Yang, G., Xu, F., Caruso, R. C., Lewis, R. A., Ziccardi, L., & Sieving, P. A. (2010) · Human Mutation · doi:10.1002/humu.21350 · Cited by 52 · see citing works
Self-citationCuenca, N., Fernández‐Sánchez, L., Sauvé, Y., Segura, F. J., MartÃnez-Navarrete, G., Tamarit, J. M., Fuentes‐Broto, L., Sánchez-Cano, A. I., & Pinilla, I. (2014) · Frontiers in Neuroanatomy · doi:10.3389/fnana.2014.00151 · Cited by 49 · see citing works
Weber, B. H. F., Schrewe, H., Molday, L. L., Gehrig, A., White, K. L., Seeliger, M. W., Jaissle, G. B., Friedburg, C., Tamm, E., & Molday, R. S. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.092528599 · Cited by 41 · see citing works
Hanitzsch, R., Lichtenberger, T., & Mättig, W.-U. (1996) · Vision Research · doi:10.1016/0042-6989(95)00140-9 · Cited by 34 · see citing works
Marangoni, D., Wu, Z., Wiley, H. E., Zeiss, C. J., Vijayasarathy, C., Zeng, Y., Hiriyanna, S., Bush, R. A., Wei, L. L., Colosi, P., et al. (2014) · Human Gene Therapy Clinical Development · doi:10.1089/humc.2014.067 · Cited by 29 · see citing works
Self-citationDyka, F. M., & Molday, R. S. (2007) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.06-1465 · Cited by 28 · see citing works
Ziccardi, L., Vijayasarathy, C., Bush, R. A., & Sieving, P. A. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.1913-12.2012 · Cited by 21 · see citing works
Self-citation
Flagged first, then by citations
1 of the 43 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Cukras, C., Wiley, H. E., Jeffrey, B. G., Sen, H. N., Turriff, A., Zeng, Y., Vijayasarathy, C., Marangoni, D., Ziccardi, L., Kjellstrom, S., et al. (2018) · Molecular Therapy · doi:10.1016/j.ymthe.2018.05.025 · Cited by 268 · see citing works
“Furthermore, a single intravitreal administration of a self-complementary AAV8-RS1 vector provided sustained therapeutic effect and RS1 expression for at least 9 months post-injection, the longest time point evaluated in the study.(10)”
BackgroundInfluentialSelf-citationViral Vectors in Gene Therapy: Where Do We Stand in 2023?
Lundstrom, K. H. (2023) · Viruses · doi:10.3390/v15030698 · Cited by 196 · see citing works
Yiu, G., Chung, S. H., Mollhoff, I. N., Nguyen, U. T., Thomasy, S. M., Yoo, J., Taraborelli, D., & Noronha, G. (2020) · Molecular Therapy - Methods & Clinical Development · doi:10.1016/j.omtm.2020.01.002 · Cited by 153 · see citing works
Gene therapy for inherited retinal diseases: Progress and possibilities
Hu, M. L., Edwards, T. L., O’Hare, F., Hickey, D. G., Wang, J.-H., Liu, Z., & Ayton, L. N. (2021) · Clinical and Experimental Optometry · doi:10.1080/08164622.2021.1880863 · Cited by 118 · see citing works
Gene Therapy in Retinal Dystrophies
Ziccardi, L., Cordeddu, V., Gaddini, L., Matteucci, A., Parravano, M., Malchiodi-Albedi, F., & Varano, M. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20225722 · Cited by 107 · see citing works
Hahn, L. C., van Schooneveld, M. J., Wesseling, N. L., Florijn, R. J., ten Brink, J. B., Lissenberg-Witte, B. I., Strubbe, I., Meester‐Smoor, M. A., Thiadens, A. A. H. J., Diederen, R. M. H., et al. (2021) · Ophthalmology · doi:10.1016/j.ophtha.2021.09.021 · Cited by 78 · see citing works
Self-citationGene Therapy in Inherited Retinal Diseases: An Update on Current State of the Art
Amato, A., Arrigo, A., Aragona, E., Manitto, M. P., Saladino, A., Bandello, F. M., & Parodi, M. B. (2021) · Frontiers in Medicine · doi:10.3389/fmed.2021.750586 · Cited by 67 · see citing works
Zhang, K. Y., & Johnson, T. V. (2021) · Experimental Eye Research · doi:10.1016/j.exer.2021.108545 · Cited by 63 · see citing works
Focused Update on AAV-Based Gene Therapy Clinical Trials for Inherited Retinal Degeneration
Fuller-Carter, P. I., Basiri, H., Harvey, A. R., & Carvalho, L. S. (2020) · BioDrugs · doi:10.1007/s40259-020-00453-8 · Cited by 41 · see citing works
Phenotypic Characteristics of a French Cohort of Patients with X-Linked Retinoschisis
Orès, R., Mohand‐Saïd, S., Dhaenens, C., Antonio, A., Zeitz, C., Augstburger, E., Andrieu, C., Sahel, J., & Audo, I. S. (2018) · Ophthalmology · doi:10.1016/j.ophtha.2018.03.057 · Cited by 38 · see citing works
Correction of Monogenic and Common Retinal Disorders with Gene Therapy
Sengillo, J. D., Justus, S., Cabral, T., & Tsang, S. H. (2017) · Genes · doi:10.3390/genes8020053 · Cited by 37 · see citing works
Wide-Field Swept-Source OCT and Angiography in X-Linked Retinoschisis
Han, I. C., Whitmore, S. S., Critser, D. B., Lee, S. Y., DeLuca, A. P., Daggett, H. T., Affatigato, L. M., Mullins, R. F., Tucker, B. A., Drack, A. V., et al. (2018) · Ophthalmology Retina · doi:10.1016/j.oret.2018.09.006 · Cited by 36 · see citing works
Vijayasarathy, C., Zeng, Y., Brooks, M. J., Fariss, R. N., & Sieving, P. A. (2020) · Human Gene Therapy · doi:10.1089/hum.2020.213 · Cited by 32 · see citing works
Self-citationOf men and mice: Human X-linked retinoschisis and fidelity in mouse modeling
Vijayasarathy, C., Pasha, S. P. B. S., & Sieving, P. A. (2021) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2021.100999 · Cited by 31 · see citing works
Self-citationAnalysis of Anatomic and Functional Measures in X-Linked Retinoschisis
Cukras, C. A., Huryn, L. A., Jeffrey, B. G., Turriff, A. E., & Sieving, P. A. (2018) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.17-23297 · Cited by 27 · see citing works
Self-citationZeng, Y., Qian, H., Campos, M. M., Li, Y., Vijayasarathy, C., & Sieving, P. A. (2021) · Gene Therapy · doi:10.1038/s41434-021-00290-6 · Cited by 25 · see citing works
Self-citationThe new landscape of retinal gene therapy
Ku, C. A., & Pennesi, M. E. (2020) · American Journal of Medical Genetics Part C Seminars in Medical Genetics · doi:10.1002/ajmg.c.31842 · Cited by 24 · see citing works
X-Linked RetinoschisisPreprint
Ku, C. A., Wei, L. W., & Sieving, P. A. (2023) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a041288 · Cited by 24 · see citing works
Self-citationHeymann, J. B., Vijayasarathy, C., Fariss, R. N., & Sieving, P. A. (2022) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2022.101147 · Cited by 23 · see citing works
Self-citationVijayasarathy, C., Zeng, Y., Marangoni, D., Dong, L., Pan, Z., Simpson, E. M., Fariss, R. N., & Sieving, P. A. (2022) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.63.11.8 · Cited by 21 · see citing works
Self-citationCampbell, M., Cassidy, P. S., O’Callaghan, J., Crosbie, D. E., & Humphries, P. (2017) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2017.09.003 · Cited by 21 · see citing works
Stephenson, K. A. J., Zhu, J., Dockery, A., Whelan, L., Burke, T. R., Turner, J., O’Byrne, J. J., Farrar, G. J., & Keegan, D. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23020995 · Cited by 20 · see citing works
Duan, C., Ding, C., Sun, X., Mao, S., Liang, Y., Liu, X., Ding, X., Chen, J., & Tang, S. (2024) · Stem Cell Research & Therapy · doi:10.1186/s13287-024-03767-4 · Cited by 20 · see citing works
Gene Therapy Cargoes Based on Viral Vector Delivery
Lundstrom, K. H. (2022) · Current Gene Therapy · doi:10.2174/1566523222666220921112753 · Cited by 19 · see citing works
Shamshad, A., Kang, C., Jenny, L. A., Persad‐Paisley, E. M., & Tsang, S. H. (2023) · Vision Research · doi:10.1016/j.visres.2023.108258 · Cited by 16 · see citing works
Advancing precision medicines for ocular disorders: Diagnostic genomics to tailored therapies
Panikker, P., Roy, S., Ghosh, A., Poornachandra, B., & Ghosh, A. (2022) · Frontiers in Medicine · doi:10.3389/fmed.2022.906482 · Cited by 16 · see citing works
Looking to the Future of Viral Vectors in Ocular Gene Therapy: Clinical Review
Kharisova, C. B., Kitaeva, K. V., Solovyeva, V. V., Sufianov, A. A., Суфианова, Г. З., Фаисович, А. Р., Bulgar, S. N., & Rizvanov, A. A. (2025) · Biomedicines · doi:10.3390/biomedicines13020365 · Cited by 15 · see citing works
van der Veen, I., Heredero Berzal, A., Koster, C., ten Asbroek, A. L. M. A., Bergen, A. A., & Boon, C. J. F. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25021267 · Cited by 14 · see citing works
Ito, M., & Ohno, K. (2018) · Matrix Biology · doi:10.1016/j.matbio.2018.02.014 · Cited by 14 · see citing works
AAV2/4-RS1 gene therapy in the retinoschisin knockout mouse model of X-linked retinoschisis
Scruggs, B. A., Bhattarai, S., Helms, M., Cherascu, I., Salesevic, A., Stalter, E., Laird, J. G., Baker, S. A., & Drack, A. V. (2022) · PLoS ONE · doi:10.1371/journal.pone.0276298 · Cited by 13 · see citing works
Translational Retinal Research and Therapies
Hardcastle, A. J., Sieving, P. A., Sahel, J., Jacobson, S. G., Cideciyan, A. V., Flannery, J. G., Beltran, W. A., & Aguirre, G. D. (2018) · Translational Vision Science & Technology · doi:10.1167/tvst.7.5.8 · Cited by 13 · see citing works
Self-citationAAVrh-10 transduces outer retinal cells in rodents and rabbits following intravitreal administration
Zeng, Y., Qian, H., Wu, Z., Marangoni, D., Sieving, P. A., & Bush, R. A. (2019) · Gene Therapy · doi:10.1038/s41434-019-0094-3 · Cited by 12 · see citing works
Self-citationSong, H., Zeng, Y., Sardar Pasha, S. P. B., Bush, R. A., Vijayasarathy, C., Qian, H., Wei, L., Wiley, H. E., Wu, Z., & Sieving, P. A. (2020) · Translational Vision Science & Technology · doi:10.1167/tvst.9.7.28 · Cited by 9 · see citing works
Self-citationRekindling Vision: Innovative Strategies for Treating Retinal Degeneration
Khan, I., Ramzan, F., Tayyab, H., & Damji, K. F. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26094078 · Cited by 9 · see citing works
X-linked Retinoschisis and Gene Therapy
Mishra, A., & Sieving, P. A. (2021) · International Ophthalmology Clinics · doi:10.1097/iio.0000000000000373 · Cited by 10 · see citing works
Self-citationHinsch, V. G., Boye, S. L., & Boye, S. E. (2025) · Human Gene Therapy · doi:10.1089/hum.2024.252 · Cited by 9 · see citing works
Application of Viruses for Gene Therapy and Vaccine Development
Lundstrom, K. H. (2022) · Advances in environmental microbiology · doi:10.1007/978-3-030-85395-2_9 · Cited by 8 · see citing works
Jin, X., Zhang, X., Liu, J., Wang, W., Liu, M., Yang, L., Liu, G., Qiu, R., Yang, M., Yao, S., et al. (2022) · Cells · doi:10.3390/cells11142150 · Cited by 8 · see citing works
Chien, Y., Wu, Y., Chen, C., Yang, Y., Ching, L., Wang, B., Chang, W., Chiang, I.-C., Su, P., Chen, S.-Y., et al. (2024) · Advanced Science · doi:10.1002/advs.202405818 · Cited by 7 · see citing works
“Para-retinal” Vector Administration into the Deep Vitreous Enhances Retinal Transgene Expression
Zeng, Y., Boyd, R. F., Bartoe, J. T., Wiley, H. E., Marangoni, D., Wei, L. L., & Sieving, P. A. (2020) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2020.06.015 · Cited by 7 · see citing works
Self-citationSubretinal Gene Therapy for X-Linked Retinoschisis
Liang, L., She, K., Ren, C., Li, R., Meng, L., Tao, Z., Liu, F., Su, J., Hu, M., Yang, Y., et al. (2026) · New England Journal of Medicine · doi:10.1056/nejmoa2515953 · Cited by 6 · see citing works
Correcting visual loss by genetics and prosthetics
Xue, K., & MacLaren, R. E. (2020) · Current Opinion in Physiology · doi:10.1016/j.cophys.2020.03.003 · Cited by 5 · see citing works
Diurnal functional and anatomical changes in X-linked retinoschisis
Mautone, L., Atiskova, Y., Druchkiv, V., Spitzer, M. S., & Dulz, S. (2023) · Graefe s Archive for Clinical and Experimental Ophthalmology · doi:10.1007/s00417-023-06106-0 · Cited by 5 · see citing works
Hassan, S., Hsu, Y., Thompson, J. M., Kalmanek, E., VandeLune, J. A., Stanley, S., & Drack, A. V. (2024) · Frontiers in Medicine · doi:10.3389/fmed.2024.1304819 · Cited by 4 · see citing works
Gehrke, E. J., Thompson, J. M., Kalmanek, E., Stanley, S. T., Laird, J. G., Bhattarai, S., Lobeck, B., Mayer, S. K., Mahoney, A., Hassan, S., et al. (2024) · Frontiers in Medicine · doi:10.3389/fmed.2024.1302119 · Cited by 4 · see citing works
Marangoni, D., Yong, Z., Kjellström, S., Vijayasarathy, C., Sieving, P. A., & Bush, R. A. (2017) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.16-21016 · Cited by 4 · see citing works
Self-citationGene Therapy for Retinal Diseases
Gopinath, C., Sarkar, S., & Ghosh, A. (2021) · Essentials in ophthalmology/Essentials ophthalmology · doi:10.1007/978-981-15-9184-6_30 · Cited by 3 · see citing works
Hassan, S., Hsu, Y., Mayer, S. K., Thomas, J., Kothapalli, A. J., Helms, M., Baker, S. A., Laird, J. G., Bhattarai, S., & Drack, A. V. (2023) · Saudi Journal of Ophthalmology · doi:10.4103/sjopt.sjopt_155_23 · Cited by 3 · see citing works
AAV-Mediated Gene Therapy for CRB1-Hereditary Retinopathies
Alves, C. H., & Wijnholds, J. (2019) · IntechOpen eBooks · doi:10.5772/intechopen.79308 · Cited by 3 · see citing works
Gene therapy for inherited retinal diseases
Dhooge, P. P. A., Valkenburg, D., & Hoyng, C. B. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-816222-4.00017-4 · Cited by 3 · see citing works
Wei, X., Ma, S., Zhou, Y., Cui, H., Zhang, S., Wang, D., Fu, Y., Li, W., Han, H., Li, Y., et al. (2025) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.66.4.37 · Cited by 2 · see citing works
Emerging Gene Therapy Treatments for Inherited Retinal Diseases
Bakall, B., Klein, K. A., & Hariprasad, S. M. (2018) · Ophthalmic surgery, lasers & imaging retina · doi:10.3928/23258160-20180628-02 · Cited by 2 · see citing works
Stem Cell and Gene Therapy for Inherited Retinal Diseases
DeSouza, P. J., Park, U. C., & Park, S. S. (2022) · Springer eBooks · doi:10.1007/978-981-16-7337-5_3 · Cited by 2 · see citing works
Jo, D. H., Jang, H., Cho, C. S., Lee, S. J., Heo, J. H., Kim, J. A., Kim, S. J., Ryu, W., Park, C.-W., Kang, B.-C., et al. (2025) · Molecular Therapy · doi:10.1016/j.ymthe.2025.04.021 · Cited by 1 · see citing works
Mordà, D., Alibrandi, S., Scimone, C., Rinaldi, C., Scalinci, S. Z., Abate, G., D’Angelo, R., Sidoti, A., & Donato, L. (2025) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2025.101405 · Cited by 2 · see citing works
Nonviral Delivery Systems for Gene Therapy for Retina and Posterior Segment Disease
del Pozo‐Rodríguez, A., Torrecilla, J., Rodríguez‐Gascón, A., & Solinís, M. Á. (2018) · Springer eBooks · doi:10.1007/978-3-319-95807-1_8 · Cited by 1 · see citing works
Administration of Ocular Gene Therapy
Xu, D. N., Khan, M., Klufas, M. A., & Ho, A. C. (2021) · International Ophthalmology Clinics · doi:10.1097/iio.0000000000000365 · Cited by 1 · see citing works
Gene Therapy, Diet and Drug Approaches to Treating Inherited Retinal Disease
Simunovic, M. P., Mack, H. G., Ayton, L. N., & Hassall, M. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-820472-6.00154-7 · Cited by 1 · see citing works
Congenital X-Linked Retinoschisis and Retinal Detachment
Özdemir, H. B., & Özdek, Ş. (2023) · Springer eBooks · doi:10.1007/978-3-031-14506-3_36 · Cited by 1 · see citing works
Sun, Y., Xiao, D., Li, Z., Xu, D., Zhang, D., An, Y., Xue, J., Ren, Y., Liu, S., Wang, D., et al. (2024) · Biochemistry and Biophysics Reports · doi:10.1016/j.bbrep.2024.101646 · Cited by 1 · see citing works
Self-citationZeng, Y., Gao, S., Li, Y., Marangoni, D., Silva, T. D., Wong, W. T., Chew, E. Y., Sun, X., Li, T., Sieving, P. A., et al. (2024) · Bioengineering · doi:10.3390/bioengineering11050449 · Cited by 1 · see citing works
Self-citationRecent advances on modeling retinal disease: Towards efficient gene/drug therapy
Dolatabadi, E. N., Zaky, M. R. A., Abbas, F. H., Milani, A. E., André, H., & Alizadeh, E. (2025) · Experimental Eye Research · doi:10.1016/j.exer.2025.110416 · Cited by 1 · see citing works
Juvenile X-Linked Retinoschisis and Hereditary Vitreoretinopathies
Cukras, C. A., Huryn, L. A., & Sieving, P. A. (2022) · Springer eBooks · doi:10.1007/978-3-030-42634-7_5 · Cited by 1 · see citing works
Self-citationLee, C. S. (2022) · Springer eBooks · doi:10.1007/978-981-16-7337-5_11 · Cited by 1 · see citing works
Ocular Gene Therapy—The Future Is Now
Huang, S. S., High, K. A., & Toso, R. (2016) · Asia-Pacific Journal of Ophthalmology · doi:10.1097/apo.0000000000000216
Kang, E. Y., & Wang, N. (2020) · Retina atlas · doi:10.1007/978-981-15-0414-3_3
Emerging Gene Therapy Approaches Under Clinical Investigation for Retinal Degenerative Diseases
Bakall, B., Klein, K. A., & Mears, K. A. (2020) · Topics in medicinal chemistry · doi:10.1007/7355_2020_102
Juvenile X-Linked Retinoschisis and Hereditary Vitreoretinopathies
Cukras, C. A., Huryn, L. A., & Sieving, P. A. (2021) · Springer eBooks · doi:10.1007/978-3-319-90495-5_5-1
Self-citationÖZÇALIŞKAN, Ş., & ÖZBEK, M. (2022) · Güncel Retina Dergisi (Current Retina Journal) · doi:10.37783/crj-0359
Ziccardi, L., & Sieving, P. A. (2025) · doi:10.1093/med/9780197659403.003.0030
Self-citationChou, S., Wang, C.-H., Chang, Y., Fang, W.-C., Hwang, D., Hsiao, Y., Luo, Y., Lo, W., Viet, N. Q., Tang, K.-Y., et al. (2025) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2025.148300
Investigating the Role of Zebrafish Retinoschisin Homologs Rs1a and Rs1b During Retinal Development
van der Veen, I., Koster, C., ten Brink, J. B., Kamermans, M., & Boon, C. J. F. (2025) · Developmental Neurobiology · doi:10.1002/dneu.23012
Duan, C., Ding, C., Sun, X., Mao, S., Liang, Y., Liu, X., Ding, X., Chen, J., & Tang, S. (2024) · Figshare · doi:10.6084/m9.figshare.26727907
Duan, C., Ding, C., Sun, X., Mao, S., Liang, Y., Liu, X., Ding, X., Chen, J., & Tang, S. (2024) · Figshare · doi:10.6084/m9.figshare.26727889
Duan, C., Ding, C., Sun, X., Mao, S., Liang, Y., Liu, X., Ding, X., Chen, J., & Tang, S. (2024) · Figshare · doi:10.6084/m9.figshare.26727901
Duan, C., Ding, C., Sun, X., Mao, S., Liang, Y., Liu, X., Ding, X., Chen, J., & Tang, S. (2024) · Figshare · doi:10.6084/m9.figshare.26727892
Duan, C., Ding, C., Sun, X., Mao, S., Liang, Y., Liu, X., Ding, X., Chen, J., & Tang, S. (2024) · Figshare · doi:10.6084/m9.figshare.26727904
Duan, C., Ding, C., Sun, X., Mao, S., Liang, Y., Liu, X., Ding, X., Chen, J., & Tang, S. (2024) · Figshare · doi:10.6084/m9.figshare.26727895
Duan, C., Ding, C., Sun, X., Mao, S., Liang, Y., Liu, X., Ding, X., Chen, J., & Tang, S. (2024) · Figshare · doi:10.6084/m9.figshare.26727910
Duan, C., Ding, C., Sun, X., Mao, S., Liang, Y., Liu, X., Ding, X., Chen, J., & Tang, S. (2024) · Figshare · doi:10.6084/m9.figshare.26727898
Duan, C., Ding, C., Sun, X., Mao, S., Liang, Y., Liu, X., Ding, X., Chen, J., & Tang, S. (2024) · Figshare · doi:10.6084/m9.figshare.26727886
Gene therapy in ophthalmology: new prospects
Kharisova, C. B., Kitaeva, K. V., Solovyeva, V. V., Фаисович, А. Р., & Rizvanov, A. A. (2026) · Kazan medical journal · doi:10.17816/kmj677044
Santos, P. J., Desta, H. T., & Zhang, M. (2024) · Bulletin of pioneering researches of medical and clinical science · doi:10.51847/ezg7hlclye
Westbay, J. H., Bigley, D. P., Sappa, S., Ayalon, A., Aweidah, H., Dignam, L. D., Martel, J. N., Beltran, W. A., Sahel, J., Byrne, L. C., et al. (2026) · Journal of Materials Chemistry B · doi:10.1039/d6tb00267f
Wang, W., Liu, J., Jin, X., Qiu, R., Yang, M., Yao, S., Liu, G., Qin, M., & Lei, B. (2026) · Scientific Reports · doi:10.1038/s41598-026-47523-5
Sauter, M. M., Noel, H. R., & Brandt, C. R. (2026) · Experimental Eye Research · doi:10.1016/j.exer.2026.111009
X-linked retinoschisis (XLRS) – A review of current scientific evidence
Grudzień, M., Raniewicz, M., Tochman-Kanty, K., Święch, A., & Mackiewicz, J. (2026) · Ophthalmology · doi:10.5114/oku/241549
- Authors
- Bush, R. A., Zeng, Y., Colosi, P., Kjellstrom, S., Hiriyanna, S., Vijayasarathy, C., Santos, M., Li, J., Wu, Z., & Sieving, P. A.
- Affiliations
- National Institutes of Health (US)
- National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland.
- National Eye Institute, National Institutes of Health, Bethesda, Maryland.
- Venue
- Human Gene Therapy
- Publisher
- SAGE Publications
- Published
- 2016-05
- Volume
- 27
- Issue
- 5
- Pages
- 376-389
- ISSN
- 1043-0342 (ISSN-L)
- 1557-7422
- PMC
- PMC4840830
- OpenAlex
- W2318885789
- Cited by
- 86
- References
- 43
- Citations by year
- 2026: 6 · 2025: 10 · 2024: 15 · 2023: 6 · 2022: 12 · 2021: 11 · 2020: 9 · 2019: 4 · 2018: 9 · 2017: 3 · 2016: 1
- FWCI
- 2.95
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Human Gene Therapy (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Funders
- National Institutes of Health
- National Eye Institute
- National Institute on Deafness and Other Communication Disorders
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Keywords
- X-linked retinoschisis, retinoschisin, intravitreal gene therapy, dose escalation, retinal function, electroretinogram, retinal structure, outer nuclear layer thickness, macular dystrophy
- MeSH terms
- Dependovirus, Animals, Disease Models, Animal, Electroretinography, Eye Proteins, Genetic Vectors, Immunohistochemistry, Male, Retina, Time Factors, Transduction, Genetic, Genetic Therapy, Cell Adhesion Molecules, Gene Expression, Mice, Knockout, Retinoschisis, Tomography, Optical Coherence, Genes, X-Linked, Mice, Intravitreal Injections
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
