Target intelligence / Profile preview

Channelrhodopsin (Engineered variants) (ChR)

Target
ChR
Molecular classification
Ion channel, Light-gated ion channel, Microbial opsin, Rhodopsin-like protein
01

Overview

Engineered channelrhodopsin variants are light-sensitive proteins derived from microorganisms, such as green algae, that have been modified for optogenetic therapy in the human retina (Sahel et al., 2021, Nature Medicine). These proteins function as light-gated ion channels that open in response to specific wavelengths of light, allowing the influx of cations like sodium and calcium to depolarize the host neuron (UniProt P69769). In the context of degenerative retinal diseases such as retinitis pigmentosa, these variants are delivered via viral vectors to bypass damaged photoreceptors and directly sensitize remaining retinal ganglion cells or bipolar cells to light (Nanoscope Therapeutics, 2024). This approach effectively transforms these surviving neurons into primary light-sensing cells, aiming to restore functional vision to patients who are otherwise blind. Clinical applications often involve the use of external light-stimulating goggles to provide the necessary intensity and wavelength required to trigger the engineered channels (Bionic Sight, 2023). Because the therapy targets downstream neurons, it is potentially independent of the specific genetic mutation causing the initial photoreceptor loss. Current research focuses on improving the light sensitivity and kinetics of these channels to allow for vision under natural light conditions without the need for high-intensity external devices.

Other names
Channelrhodopsin-2ChR2ChrimsonRMulti-Characteristic OpsinMCO-010Optogenetic actuatorLight-gated ion channelMicrobial opsin
02

Mechanism of action

Light-activated cation influx leading to neuronal depolarization and signal transmission to the visual cortex.

03

Biological functions

PhototransductionIon transportMembrane depolarizationNeural signalingOptogenetic control
04

Disease associations

Retinitis pigmentosaStargardt diseaseMacular degenerationInherited retinal dystrophyGeographic atrophy
05

Safety considerations

Intraocular inflammation (uveitis)Immune response to viral vector (AAV)Immune response to microbial proteinLight-induced retinal toxicity from stimulation devicesOff-target expression in non-neuronal cells
06

Interacting drugs

GS030 (GenSight Biologics)

3 more in the full profile.

07

Biomarkers

Best-corrected visual acuity (BCVA)Multi-Luminance Mobility Test (MLMT)Full-field Stimulus Threshold (FST)Optical Coherence Tomography (OCT)Electroretinography (ERG)

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