Variant Opsins for Neural Control via Segmentation and Parameter Changes
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
There is a need for effective depolarizing and hyperpolarizing optogenetic tools to control neural activity, which current technologies have not adequately addressed.
Innovation Solution
The development of variant opsins with increased activity and/or increased trafficking to the plasma membrane, including specific opsin polypeptides and nucleic acids encoding these opsins, which can be used to modulate cellular processes and voltage potentials in therapeutic and screening applications.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If conventional opsins are used for optogenetic control, then basic light-sensitive function is achieved, but depolarizing andhyperpolarizing control capabilities are insufficient
Solution Approach 1:
The invention segments the opsin functional requirements into distinct depolarizing andhyperpolarizing tools, creating specialized variants for each control mode. This segmentation allows independent optimization of each tool's performance characteristics, resolving the contradiction between versatility and reliability by providing dedicated solutions for specific neural control needs
Solution Approach 2:
The invention employs parameter changes by modifying amino acid sequences of opsins to alter their functional properties. Specific mutations are introduced to change ion selectivity, conductance, and light sensitivity parameters, enabling the creation of variant opsins with enhanced depolarizing andhyperpolarizing capabilities while maintaining reliable neural control
2Measurement precision
If opsin activity is increased to improve control precision, then neural control precision is improved, but trafficking to plasma membrane may be reduced
Solution Approach 1:
The invention applies preliminary action by optimizing the signal sequence and N-terminal region of opsins before the protein reaches the plasma membrane. These preliminary modifications ensure proper folding, trafficking signals, and membrane localization are established in advance, preventing loss of membrane localization when activity is enhanced through subsequent mutations
Solution Approach 2:
The invention uses parameter changes by carefully selecting mutations that affect activity without disrupting trafficking parameters. By changing specific amino acid parameters involved in ion channel function while preserving parameters related to membrane targeting signals, the invention achieves improved control precision while maintaining reliable plasma membrane localization
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
These variant opsins enable precise control of cellular processes and neural activity by modulating voltage potentials, providing effective therapeutic and screening tools for various applications, including the treatment of neurological disorders and drug development.
Implementation Method 1
7-transmembrane rhodopsins that can be found across all kingdoms of life and serve a diverse range of functions
Implementation Method 2
the development of cellular perturbation tools based on these and other light sensitive proteins has resulted in a technology called optogenetics, referring to the integration of genetic and optical control to achieve gain- or loss-of-function of precisely defined events within specified cells of living tissue
Data Source
AI summary
The present disclosure provides opsins, including variant opsins with increased activity and/or increased trafficking to the plasma membrane. The opsins are useful in therapeutic and screening applications, which are also provided.