Description:
When expressed in targeted neurons, light-sensitive channelrhodopsin proteins (ChRs) have the ability to selectively manipulate neuronal activity in a light-dependent manner. Kalium (potassium)-conducting channelrhodopsins (KCRs) have the potential for optogenetic applications and as therapeutic agents for electrically active cell mediated disorders, while cation ChRs (CCRs) hold promise for vision restoration.
Dr. John Spudich and his team at UTHealth have developed suites of CCRs and KCRs, which are orders of magnitude more efficient than currently available optogenetic tools and are promising for the potential treatment of potassium channelopathies such as epilepsy, Parkinson's disease and long-QT syndrome and other cardiac arrhythmias.
Technology Overview
- Kalium ChRs (KCRs) that
- Light-gated and have independently evolved an alternative K+ selectivity mechanism
- Potent, highly selective of K+ over Na+, and open in less than 1 ms following photoactivation
- The permeability ratio PK/PNa of 23 makes H. catenoides KCR1 (HcKCR1) a powerful hyperpolarizing tool to suppress excitable cell firing upon illumination
Fig. KCRs is a potent optogenetic silencer of mouse cortical neurons
- Cation ChRs (CCRs) containing mutations of the transmembrane helix 4 with
- Superior photocurrent amplitudes
- Enhanced Na+ selectivity
- Enhanced Ca2+ conductance
Clinical Applications
Our ChRs have the potential to be used as gene therapy-based therapeutics for diseases caused by aberrant neuronal activity or other cellular excitation, such asepilepsy, Parkinson's disease and long-QT syndrome and other cardiac arrhythmias.
Intellectual Property Status
Issued and pending US patents on suites of CCRs and KCRs are available for licensing :
Selected Publications
- Nat Commun. 2023 Jul 20;14(1):4365. PMID: 37474513
- Nat Neurosci. 2022 Jul; 25(7):967-974. PMID: 35726059
- mBio. 2011 Jun 21; 2(3):e00115-11. PMID: 21693637
About the Investigator: Dr. John L. Spudich
- Professor of Department of Biochemistry and Molecular Biology;
- Director of Center for Membrane biology;
- Robert A. Welch Distinguished Chair in Chemistry at UTHealth
UTHealth Ref. No.: 2011-0037 (CCR) & 2022-0025 (KCR)