Light-Responsive Polypeptides for High-Speed Neural Modulation
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Solution Overview
Problem
Current optogenetic methods for controlling neuronal activity are limited by slow kinetics and limited frequency of action potential induction in response to light stimulation, which restricts the precision and efficiency of neural modulation.
Innovation Solution
Development of variant light-activated polypeptides with enhanced kinetics and amino acid sequence modifications, such as the E163S substitution, that exhibit faster channel closure and higher frequency action potential induction when exposed to light in the 600-700 nm wavelength range, along with associated nucleic acids, expression vectors, and systems for targeted cellular delivery.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Speed
If conventional optogenetic tools are used, then neuronal activity can be controlled, but the kinetics are slow and action potential induction frequency is limited
Solution Approach 1:
The patent applies parameter changes by modifying the amino acid sequence of the light-activated polypeptide (specifically the E163S substitution) to alter the kinetic properties of the channel closure, achieving at least 5-fold increased kinetics while maintaining functional reliability for action potential induction
2Manufacturing precision
If existing light-activated polypeptides are used, then membrane potential can be changed, but the precision and efficiency of neural modulation is restricted
Solution Approach 1:
The patent improves precision and efficiency of neural modulation through amino acid sequence modifications that enhance the speed and reliability of action potential induction, allowing for more precise temporal control of neuronal activity
Solution Approach 2:
The patent replaces conventional optogenetic tools with a genetically encoded light-activated polypeptide system that directly converts light energy to electrical signals in neurons, eliminating the need for external mechanical stimulation devices and improving both precision and efficiency
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The variant light-activated polypeptides achieve at least 5-fold increased kinetics and higher frequency action potential induction compared to existing optogenetic tools, enabling more precise and efficient modulation of neuronal activity.
Implementation Method 1
light-activated proteins to change the membrane voltage potentials of excitable cells, such as neurons, upon exposure to light of various wavelengths
Data Source
AI summary
The present disclosure provides variant light-responsive polypeptides, and nucleic acids comprising nucleotide sequences encoding the light-responsive polypeptides. The present disclosure provides methods, devices, and systems for controlling the activity of a cell expressing a variant light-responsive polypeptide of the present disclosure.