A clinically viable approach to restoring visual function using optogenetic gene therapy DOI Creative Commons
Boyuan Yan, Suresh Viswanáthan, Scott E. Brodie

et al.

Molecular Therapy — Methods & Clinical Development, Journal Year: 2023, Volume and Issue: 29, P. 406 - 417

Published: May 9, 2023

Optogenetic gene therapies offer a promising strategy for restoring vision to patients with retinal degenerative diseases, such as retinitis pigmentosa (RP). Several clinical trials have begun in this area using different vectors and optogenetic proteins (Clinical Identifiers: NCT02556736, NCT03326336, NCT04945772, NCT04278131). Here we present preclinical efficacy safety data the NCT04278131 trial, which uses an AAV2 vector Chronos protein. Efficacy was assessed mice dose-dependent manner electroretinograms (ERGs). Safety rats, nonhuman primates, mice, several tests, including immunohistochemical analyses cell counts (rats), (nonhuman primates), ocular toxicology assays (mice). The results showed that Chronos-expressing were efficacious over broad range of doses stimulating light intensities, well tolerated: no test article-related findings observed anatomical electrophysiological performed.

Language: Английский

Partial recovery of visual function in a blind patient after optogenetic therapy DOI Open Access
José‐Alain Sahel,

Élise Boulanger-Scemama,

Chloé Pagot

et al.

Nature Medicine, Journal Year: 2021, Volume and Issue: 27(7), P. 1223 - 1229

Published: May 24, 2021

Language: Английский

Citations

512
Optogenetics for light control of biological systems DOI
Valentina Emiliani, Emilia Entcheva, Rainer Hedrich

et al.

Nature Reviews Methods Primers, Journal Year: 2022, Volume and Issue: 2(1)

Published: July 21, 2022

Language: Английский

Citations

271
Early and late stage gene therapy interventions for inherited retinal degenerations DOI Creative Commons
Catherine Botto, Marco Rucli,

Muge Tekinsoy

et al.

Progress in Retinal and Eye Research, Journal Year: 2021, Volume and Issue: 86, P. 100975 - 100975

Published: May 29, 2021

Inherited and age-related retinal degeneration is the hallmark of a large group heterogeneous diseases main cause untreatable blindness today. Genetic factors play major pathogenic role in degenerations for both monogenic (such as retinitis pigmentosa) complex with established genetic risk macular degeneration). Progress genotyping techniques back eye imaging are completing our understanding these their manifestations patient populations suffering from degenerations. It clear that whatever cause, majority vision loss results photoreceptor function. The timing circumstances surrounding function determine adequate therapeutic approach to use each patient. Among such approaches, gene therapy rapidly becoming reality applicable clinic. This massive move laboratory work towards clinical application has been propelled by advances disease genetics mechanisms, delivery vectors, editing systems, compensatory strategies Here, we provide an overview existing modalities relevance based on needs inherited

Language: Английский

Citations

138
Monolithic silicon for high spatiotemporal translational photostimulation DOI
Pengju Li, Jing Zhang, Hidenori Hayashi

et al.

Nature, Journal Year: 2024, Volume and Issue: 626(8001), P. 990 - 998

Published: Feb. 21, 2024

Language: Английский

Citations

41
Bioengineering strategies for restoring vision DOI
Jasmina Cehajic‐Kapetanovic, Mandeep S. Singh, Eberhart Zrenner

et al.

Nature Biomedical Engineering, Journal Year: 2022, Volume and Issue: 7(4), P. 387 - 404

Published: Jan. 31, 2022

Language: Английский

Citations

57
Red Light Optogenetics in Neuroscience DOI Creative Commons
K. Lehtinen, Miriam S. Nokia, Heikki Takala

et al.

Frontiers in Cellular Neuroscience, Journal Year: 2022, Volume and Issue: 15

Published: Jan. 3, 2022

Optogenetics, a field concentrating on controlling cellular functions by means of light-activated proteins, has shown tremendous potential in neuroscience. It possesses superior spatiotemporal resolution compared to the surgical, electrical, and pharmacological methods traditionally used studying brain function. A multitude optogenetic tools for neuroscience have been created that, example, enable control action generation via ion channels. Other proteins brain, long-term potentiation or ablate specific subtypes neurons. In vivo applications, however, majority are operated with blue, green, yellow light, which all limited penetration biological tissues red light especially infrared light. This difference is significant, considering size rodent major research model Our review will focus utilization light-operated We first outline advantages studies. Then we provide brief overview systems new developments field. Finally, highlight different further facilitate use optogenetics

Language: Английский

Citations

39
Smart contact lens systems for ocular drug delivery and therapy DOI

Tae Yeon Kim,

Geon‐Hui Lee,

Jonghwan Mun

et al.

Advanced Drug Delivery Reviews, Journal Year: 2023, Volume and Issue: 196, P. 114817 - 114817

Published: April 1, 2023

Language: Английский

Citations

37
Gene-agnostic therapeutic approaches for inherited retinal degenerations DOI Creative Commons

Molly C. John,

Joel Quinn, Monica L. Hu

et al.

Frontiers in Molecular Neuroscience, Journal Year: 2023, Volume and Issue: 15

Published: Jan. 9, 2023

Inherited retinal diseases (IRDs) are associated with mutations in over 250 genes and represent a major cause of irreversible blindness worldwide. While gene augmentation or editing therapies could address the underlying genetic small subset patients, their utility remains limited by great heterogeneity IRDs costs developing individualised therapies. Gene-agnostic therapeutic approaches target common pathogenic pathways that drive degeneration provide functional rescue vision independent cause, thus offering potential clinical benefits to all IRD patients. Here, we review key gene-agnostic approaches, including cell reprogramming replacement, neurotrophic support, immune modulation optogenetics. The relative limitations these strategies timing interventions discussed.

Language: Английский

Citations

25
ENHANCED RESTORATION OF VISUAL CODE AFTER TARGETING ON BIPOLAR CELLS COMPARED TO RETINAL GANGLION CELLS WITH OPTOGENETIC THERAPY DOI Creative Commons
Jessica Rodgers, Steven Hughes, Aghileh S. Ebrahimi

et al.

Molecular Therapy, Journal Year: 2025, Volume and Issue: 33(3), P. 1264 - 1281

Published: Jan. 18, 2025

Language: Английский

Citations

1
Evolution of Light-Sensitive Proteins in Optogenetic Approaches for Vision Restoration: A Comprehensive Review DOI Creative Commons
Kamil Poboży, Tomasz Poboży, Paweł Domański

et al.

Biomedicines, Journal Year: 2025, Volume and Issue: 13(2), P. 429 - 429

Published: Feb. 10, 2025

Retinal degenerations, such as age-related macular degeneration and retinitis pigmentosa, present significant challenges due to genetic heterogeneity, limited therapeutic options, the progressive loss of photoreceptors in advanced stages. These are compounded by difficulties precisely targeting residual retinal neurons ensuring sustained efficacy interventions. Optogenetics offers a novel approach vision restoration inducing light sensitivity through gene delivery light-sensitive opsins. This review traces evolution opsins optogenetic therapies, highlighting advancements from early research on channelrhodopsin-2 (ChR2) engineered variants addressing key limitations. Red-shifted opsins, including ReaChR ChrimsonR, reduced phototoxicity enabling activation under longer wavelengths, while Chronos introduced superior temporal kinetics for dynamic visual tracking. Further innovations, Multi-Characteristic Opsin 1 (MCO1), optimized opsin performance ambient light, bridging gap real-world applications. Key milestones include first partial human patient using ChrimsonR with light-amplifying goggles ongoing clinical trials exploring opsin-based therapies degeneration. While progress has been made, remain achieving sufficient functional normal lighting conditions manner that is both effective safe, eliminating need external light-enhancing devices. As progresses, positioned redefine management degenerative diseases, offering new hope millions affected loss.

Language: Английский

Citations

1