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704 results on '"Aguirre, Gustavo D."'

5. scAAVengr, a transcriptome-based pipeline for quantitative ranking of engineered AAVs with single-cell resolution

Author

Öztürk, Bilge E, Johnson, Molly E, Kleyman, Michael, Turunç, Serhan, He, Jing, Jabalameli, Sara, Xi, Zhouhuan, Visel, Meike, Dufour, Valérie L, Iwabe, Simone, Marinho, Felipe Pompeo, Aguirre, Gustavo D, Sahel, José-Alain, Schaffer, David V, Pfenning, Andreas R, Flannery, John G, Beltran, William A, Stauffer, William R, and Byrne, Leah C

Subjects
Medical Biotechnology, Biomedical and Clinical Sciences, Genetics, Biotechnology, Neurosciences, Eye Disease and Disorders of Vision, Gene Therapy, Development of treatments and therapeutic interventions, 5.2 Cellular and gene therapies, Inflammatory and immune system, Animals, Dependovirus, Gene Expression Profiling, Genetic Vectors, Macaca fascicularis, Retina, Transcriptome, Transduction, Genetic, macaca fascicularis, callithrix jacchus, scRNA-Seq, retinal degeneration, adeno-associated virus, Rhesus macaque, Other, medicine, neuroscience, rhesus macaque, Biochemistry and Cell Biology, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

BackgroundAdeno-associated virus (AAV)-mediated gene therapies are rapidly advancing to the clinic, and AAV engineering has resulted in vectors with increased ability to deliver therapeutic genes. Although the choice of vector is critical, quantitative comparison of AAVs, especially in large animals, remains challenging.MethodsHere, we developed an efficient single-cell AAV engineering pipeline (scAAVengr) to simultaneously quantify and rank efficiency of competing AAV vectors across all cell types in the same animal.ResultsTo demonstrate proof-of-concept for the scAAVengr workflow, we quantified - with cell-type resolution - the abilities of naturally occurring and newly engineered AAVs to mediate gene expression in primate retina following intravitreal injection. A top performing variant identified using this pipeline, K912, was used to deliver SaCas9 and edit the rhodopsin gene in macaque retina, resulting in editing efficiency similar to infection rates detected by the scAAVengr workflow. scAAVengr was then used to identify top-performing AAV variants in mouse brain, heart, and liver following systemic injection.ConclusionsThese results validate scAAVengr as a powerful method for development of AAV vectors.FundingThis work was supported by funding from the Ford Foundation, NEI/NIH, Research to Prevent Blindness, Foundation Fighting Blindness, UPMC Immune Transplant and Therapy Center, and the Van Sloun fund for canine genetic research.

Published
2021

11. Translational Retinal Research and Therapies.

Author

Hardcastle, Alison J, Sieving, Paul A, Sahel, José-Alain, Jacobson, Samuel G, Cideciyan, Artur V, Flannery, John G, Beltran, William A, and Aguirre, Gustavo D

Subjects
Leber congenital amaurosis, X-linked Retinoschisis, animal models, retinitis pigmentosa, Biomedical Engineering, Opthalmology and Optometry
Abstract

The following review summarizes the state of the art in representative aspects of gene therapy/translational medicine and evolves from a symposium held at the School of Veterinary Medicine, University of Pennsylvania on November 16, 2017 honoring Dr. Gustavo Aguirre, recipient of ARVO's 2017 Proctor Medal. Focusing on the retina, speakers highlighted current work on moving therapies for inherited retinal degenerative diseases from the laboratory bench to the clinic.

Published
2018

20. Restoration of visual function by expression of a light-gated mammalian ion channel in retinal ganglion cells or ON-bipolar cells

Author

Gaub, Benjamin M, Berry, Michael H, Holt, Amy E, Reiner, Andreas, Kienzler, Michael A, Dolgova, Natalia, Nikonov, Sergei, Aguirre, Gustavo D, Beltran, William A, Flannery, John G, and Isacoff, Ehud Y

Subjects
Neurosciences, Neurodegenerative, Eye Disease and Disorders of Vision, Eye, Animals, Blindness, Ion Channel Gating, Ion Channels, Light, Mice, Mice, Inbred C3H, Mice, Inbred C57BL, Retinal Ganglion Cells, Vision, Ocular, retinal gene therapy, visual prosthetics, retinitis pigmentosa, optogenetic pharmacology, azobenzene photoswitches
Abstract

Most inherited forms of blindness are caused by mutations that lead to photoreceptor cell death but spare second- and third-order retinal neurons. Expression of the light-gated excitatory mammalian ion channel light-gated ionotropic glutamate receptor (LiGluR) in retinal ganglion cells (RGCs) of the retina degeneration (rd1) mouse model of blindness was previously shown to restore some visual functions when stimulated by UV light. Here, we report restored retinal function in visible light in rodent and canine models of blindness through the use of a second-generation photoswitch for LiGluR, maleimide-azobenzene-glutamate 0 with peak efficiency at 460 nm (MAG0(460)). In the blind rd1 mouse, multielectrode array recordings of retinal explants revealed robust and uniform light-evoked firing when LiGluR-MAG0(460) was targeted to RGCs and robust but diverse activity patterns in RGCs when LiGluR-MAG0(460) was targeted to ON-bipolar cells (ON-BCs). LiGluR-MAG0(460) in either RGCs or ON-BCs of the rd1 mouse reinstated innate light-avoidance behavior and enabled mice to distinguish between different temporal patterns of light in an associative learning task. In the rod-cone dystrophy dog model of blindness, LiGluR-MAG0(460) in RGCs restored robust light responses to retinal explants and intravitreal delivery of LiGluR and MAG0(460) was well tolerated in vivo. The results in both large and small animal models of photoreceptor degeneration provide a path to clinical translation.

Published
2014

23. Photoreceptor Outer Segment Isolation from a Single Canine Retina for RPE Phagocytosis Assay

Author

Sudharsan, Raghavi, Elliott, Michael H., Dolgova, Natalia, Aguirre, Gustavo D., Beltran, William A., COHEN, IRUN R., Series Editor, LAJTHA, ABEL, Series Editor, LAMBRIS, JOHN D., Series Editor, PAOLETTI, RODOLFO, Series Editor, REZAEI, NIMA, Series Editor, Ash, John D., editor, Anderson, Robert E., editor, LaVail, Matthew M., editor, Bowes Rickman, Catherine, editor, Hollyfield, Joe G., editor, and Grimm, Christian, editor

Published
2018
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24. Underdeveloped RPE Apical Domain Underlies Lesion Formation in Canine Bestrophinopathies

Author

Guziewicz, Karina E., McTish, Emily, Dufour, Valerie L., Zorych, Kathryn, Dhingra, Anuradha, Boesze-Battaglia, Kathleen, Aguirre, Gustavo D., COHEN, IRUN R., Series Editor, LAJTHA, ABEL, Series Editor, LAMBRIS, JOHN D., Series Editor, PAOLETTI, RODOLFO, Series Editor, REZAEI, NIMA, Series Editor, Ash, John D., editor, Anderson, Robert E., editor, LaVail, Matthew M., editor, Bowes Rickman, Catherine, editor, Hollyfield, Joe G., editor, and Grimm, Christian, editor

Published
2018
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28. Optimization of Retinal Gene Therapy for X-Linked Retinitis Pigmentosa Due to RPGR Mutations

Author

Beltran, William A., Cideciyan, Artur V., Boye, Shannon E., Ye, Guo-Jie, Iwabe, Simone, Dufour, Valerie L., Marinho, Luis Felipe, Swider, Malgorzata, Kosyk, Mychajlo S., Sha, Jin, Boye, Sanford L., Peterson, James J., Witherspoon, C. Douglas, Alexander, John J., Ying, Gui-Shuang, Shearman, Mark S., Chulay, Jeffrey D., Hauswirth, William W., Gamlin, Paul D., Jacobson, Samuel G., and Aguirre, Gustavo D.

Published
2017
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29. Therapeutic Neonatal Hepatic Gene Therapy in Mucopolysaccharidosis VII Dogs

Author

Ponder, Katherine Parker, Melniczek, John R., Xu, Lingfei, Weil, Margaret A., O'Malley, Thomas M., O'Donnell, Patricia A., Knox, Van W., Aguirre, Gustavo D., Mazrier, Hamutal, Ellinwood, N. Matthew, Sleeper, Meg, Maguire, Albert M., Volk, Susan W., Mango, Robert L., Zweigle, Jean, Wolfe, John H., and Haskins, Mark E.

Published
2002

44. RPGRIP1 and Cone–Rod Dystrophy in Dogs

Author

Kuznetsova, Tatyana, Zangerl, Barbara, Aguirre, Gustavo D., LaVail, Matthew M., editor, Ash, John D., editor, Anderson, Robert E., editor, Hollyfield, Joe G., editor, and Grimm, Christian, editor

Published
2012
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46. Photoreceptor Function and Structure in Autosomal Dominant Vitelliform Macular Dystrophy Caused by BEST1 Mutations

Author

Cideciyan, Artur V., primary, Jacobson, Samuel G., additional, Swider, Malgorzata, additional, Sumaroka, Alexander, additional, Sheplock, Rebecca, additional, Krishnan, Arun K., additional, Garafalo, Alexandra V., additional, Guziewicz, Karina E., additional, Aguirre, Gustavo D., additional, Beltran, William A., additional, and Heon, Elise, additional

Published
2022
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