The DOI matches its Crossref record; 8 of the 8 references it cites were found in a registry or an index.
Human gene therapy for RPE65 isomerase deficiency activates the retinoid cycle of vision but with slow rod kinetics
Open accessAbstract
The RPE65 gene encodes the isomerase of the retinoid cycle, the enzymatic pathway that underlies mammalian vision. Mutations in RPE65 disrupt the retinoid cycle and cause a congenital human blindness known as Leber congenital amaurosis (LCA). We used adeno-associated virus-2-based RPE65 gene replacement therapy to treat three young adults with RPE65 -LCA and measured their vision before and up to 90 days after the intervention. All three patients showed a statistically significant increase in visual sensitivity at 30 days after treatment localized to retinal areas that had received the vector. There were no changes in the effect between 30 and 90 days. Both cone- and rod-photoreceptor-based vision could be demonstrated in treated areas. For cones, there were increases of up to 1.7 log units (i.e., 50 fold); and for rods, there were gains of up to 4.8 log units (i.e., 63,000 fold). To assess what fraction of full vision potential was restored by gene therapy, we related the degree of light sensitivity to the level of remaining photoreceptors within the treatment area. We found that the intervention could overcome nearly all of the loss of light sensitivity resulting from the biochemical blockade. However, this reconstituted retinoid cycle was not completely normal. Resensitization kinetics of the newly treated rods were remarkably slow and required 8 h or more for the attainment of full sensitivity, compared with <1 h in normal eyes. Cone-sensitivity recovery time was rapid. These results demonstrate dramatic, albeit imperfect, recovery of rod- and cone-photoreceptor-based vision after RPE65 gene therapy.
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Cites
Safety and Efficacy of Gene Transfer for Leber's Congenital Amaurosis
Maguire, A. M., Simonelli, F., Pierce, E. A., Pugh, E. N., Mingozzi, F., Bennicelli, J., Banfi, S., Marshall, K. A., Testa, F., Surace, E. M., et al. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa0802315 · Cited by 2,145
Self-citationEffect 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
Gene therapy restores vision in a canine model of childhood blindness
Acland, G. M., Aguirre, G. D., Ray, J., Zhang, Q., Aleman, T. S., Cideciyan, A. V., Pearce-Kelling, S. E., Anand, V., Zeng, Y., Maguire, A. M., et al. (2001) · Nature Genetics · doi:10.1038/ng0501-92 · Cited by 1,202 · cited 13×
“We used adeno-associated virus-2-based RPE65 gene replacement therapy to treat three young adults with RPE65-LCA and measured their vision before and up to 90 days after the intervention.”
BackgroundInfluentialSelf-citationEffective gene therapy with nonintegrating lentiviral vectors
Yáñez-Muñoz, R. J., Balaggan, K. S., MacNeil, A., Howe, S. J., Schmidt, M., Smith, A. J., Buch, P., MacLaren, R. E., Anderson, P. N., Barker, S. E., et al. (2006) · Nature Medicine · doi:10.1038/nm1365 · Cited by 460
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
Jacobson, S. G., Acland, G. M., Aguirre, G. D., Aleman, T. S., Schwartz, S. B., Cideciyan, A. V., Zeiss, C. J., Komaromy, A. M., Kaushal, S., Roman, A. J., et al. (2006) · Molecular Therapy · doi:10.1016/j.ymthe.2006.03.005 · Cited by 224
Self-citationZhang, H., Fan, J., Li, S., Karan, S., Rohrer, B., Palczewski, K., Frederick, J. M., Crouch, R. K., & Baehr, W. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.0317-08.2008 · Cited by 101
RPE65 Gene Delivery Restores Isomerohydrolase Activity and Prevents Early Cone Loss in Rpe65−/−Mice
Chen, Y., Moiseyev, G., Takahashi, Y., & Ma, J.-X. (2006) · Investigative Opthalmology & Visual Science · doi:10.1167/iovs.05-0965 · Cited by 80
Cited by
Adeno-associated virus vector as a platform for gene therapy delivery
Wang, D., Tai, P. W. L., & Gao, G. (2019) · Nature Reviews Drug Discovery · doi:10.1038/s41573-019-0012-9 · Cited by 2,444
Effect of genome size on AAV vector packaging
Wu, Z., Yang, H., & Colosi, P. (2010) · Molecular Therapy · doi:10.1038/mt.2009.255 · Cited by 1,029
Immune responses to AAV vectors: overcoming barriers to successful gene therapy
Mingozzi, F., & High, K. A. (2013) · Blood · doi:10.1182/blood-2013-01-306647 · Cited by 955
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
Self-citationDalkara, D., Byrne, L. C., Klimczak, R. R., Visel, M., Yin, L., Merigan, W. H., Flannery, J. G., & Schaffer, D. V. (2013) · Science Translational Medicine · doi:10.1126/scitranslmed.3005708 · Cited by 734
Metadata
- Authors
- Cideciyan, A. V., Aleman, T. S., Boye, S. L., Schwartz, S. B., Kaushal, S., Roman, A. J., Pang, J.-J., Sumaroka, A., Windsor, E. A. M., Wilson, J. M., Flotte, T. R., Fishman, G. A., Heon, E., Stone, E. M., Byrne, B. J., Jacobson, S. G., & Hauswirth, W. W.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2008-09-30
- Volume
- 105
- Issue
- 39
- Pages
- 15112-15117
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2022040013
- Cited by
- 673
- References
- 8
- FWCI
- 22.33
- Type
- journal article
- Language
- en
- Open access
- green
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- Cideciyan, A. V., Aleman, T. S., Boye, S. L., Schwartz, S. B., Kaushal, S., Roman, A. J., Pang, J.-J., Sumaroka, A., Windsor, E. A. M., Wilson, J. M., Flotte, T. R., Fishman, G. A., Heon, E., Stone, E. M., Byrne, B. J., Jacobson, S. G., & Hauswirth, W. W. (2008). Human gene therapy for RPE65 isomerase deficiency activates the retinoid cycle of vision but with slow rod kinetics. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0807027105
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
