Novel Channelrhodopsins for Inhibition of Neuronal Activity

Description:

Optogenetics is rapidly evolving field that provides the ability to control neurons using light-sensitive proteins called channelrhodopsins (ChRs). When genetically expressed in neurons, ChRs have the ability to selectively manipulate neuronal activity in a light-dependent manner. Gene-therapy using ChRs has the exciting potential to be used to treat patients suffering from disorders caused by aberrant neuronal signaling. Dr. John L. Spudich and his research team have disrupted the field of optogenetics through their discovery and development of first of their kind anion channelrhodopsins (ACRs). These ACRs are orders of magnitude more efficient than any other optogenetic tools currently available and have the unprecedented ability to effectively inhibit neuron firing. Development of the ACRs into gene therapy based therapeutics, may potentially open new avenues for treating excessive neuron firing in conditions such as Parkinson’s disease, neuropathic pain and epilepsy.

 

Technology Overview

Dr. John L. Spudich and his research team have discovered a novel family of light-gated anion channel proteins derived from algae, anion channelrhodopsins (ACRs). When genetically expressed in neurons the humanized functional rhodopsin domains of these ACRs induce membrane hyperpolarization, and as a result induce neuronal silencing, in a light-dependent manner.

 

Potential Applications

The rhodopsin domain of these ACRs have the potential to be used as gene therapy based therapeutics for diseases caused by overactive neurons, such as:

- Parkinson's Disease       - Neuropathic Pain              - Cardiac Disorders

- Epilepsy                       - Ocular Disorders

 

Technology Advantages

The ACRs overcome the inefficiencies of previously available optogenetic tools by providing:

  1. neuronal inhibition orders of magnitude greater than previously characterized optogenetic silencing proteins (i.e. archaerhodopsin-3 and CholC mutant); and
  2. extremely high light-sensitivity, absolute anion selectivity (i.e. chloride ions) and rapid kinetics.

Stage of Development

The investigators have humanized several ACRs and have successfully expressed the modified proteins in mammalian cells. In addition to discovering new ACRs, the investigators are probing the molecular mechanism of action of identified ACR proteins.

 

Intellectual Property Status

•  ACR patent applications are pending.

•  ACR portfolio is available for licensing.

•  Non-ACR patents and patent applications for optogenetic tools are also available for licensing.

 

Associated Publications

• Science. 2015 Aug 7;349(6248):647-50. PMID:26113638

• Proc. Natl. Acad. Sci. USA. 2015 Nov 17; 112(46):14236-41. PMID:26578767

• Photochem Photobiol. 2015 Dec. PMID: 26686819

 

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Patent Information:

The preceding is intended to be a non-confidential and limited description of a novel technology created at the University of Texas Health Science Center at Houston (UTHealth). This promotional material is not comprehensive in scope and should not replace company’s diligence in a thorough evaluation of the technology. Please contact the Office of Technology Management for more information regarding this technology.
For Information, Contact:
Hannah Nelson
Senior Technology License Associate
University of Texas Health Science Center At Houston
hannah.m.nelson@uth.tmc.edu
Inventors:
John Spudich
Elena G Govorunova
Oleg A Sineshchekov
Keywords:
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