Mutated Channelrhodopsin Protein Low Light Photosensitivity
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Solution Overview
Problem
Current treatments for retinitis pigmentosa and age-related macular degeneration using channelrhodopsin2 (ChR2) from algae are insufficient due to low photosensitivity, particularly at low light intensities, limiting the restoration of visual function.
Innovation Solution
Development of a high photosensitivity light-gated cation channel protein derived from Guillardia theta, with specific mutations at defined positions, enhancing channel activity and opening ratio, and its application in retinal ganglion and bipolar cells to restore visual function.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If channelrhodopsin2 (ChR2) from algae is used for visual function restoration, then photoreceptive capability is imparted to retinal ganglion cells, but photosensitivity is insufficient at low light intensities
Solution Approach 1:
The patent applies parameter changes by introducing specific amino acid substitutions at defined positions in the channelrhodopsin protein sequence. These substitutions modify the protein's photosensitivity parameters, enabling effective activation at lower light intensities while maintaining channel function. The systematic variation of amino acid residues at critical positions optimizes the protein's response to low light conditions.
Solution Approach 2:
The patent applies local quality by making targeted amino acid substitutions at specific positions (e.g., positions 94, 98, 102, 110, 113, 114, 162, 224, 225, 230, 231, 235) rather than uniformly modifying the entire protein. This localized modification approach optimizes photosensitivity at critical functional sites while preserving overall protein structure and channel activity.
2Power
If high light intensity is used to activate ChR2, then channel activity is sufficient, but visual function restoration is not achievable in low light conditions such as indoors or at night
Solution Approach 1:
The patent modifies the light intensity parameter requirement by changing the protein's photosensitivity characteristics through amino acid substitutions. This allows the channel to achieve sufficient activation power at lower light intensities, expanding the range of environmental conditions under which visual function restoration can occur.
Solution Approach 2:
The patent creates modified versions (mutants) of the original channelrhodopsin protein that replicate and enhance desirable properties. These mutant proteins copy the fundamental channel function while improving photosensitivity, effectively creating optimized variants that perform better under low light conditions.
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 mutated channelrhodopsin proteins exhibit significantly improved channel activity and photosensitivity, enabling effective visual function restoration even at low light levels, surpassing the limitations of ChR2-based treatments.
Implementation Method 1
ChR2 is a light-gated cation channel (photoreceptor protein) that, when illuminated, takes in (transports) Na+ and Ca2+ from outside the cell to inside the cell, or from inside the cell to outside the cell.
Data Source
AI summary
An excellent photosensitivity is exhibited by a protein including, at a position or positions corresponding to one or two or more positions selected from the group made of the following (1) to (3) in a first amino acid sequence represented by SEQ ID NO: 1: (1) positions 39, 94, 98, 102, 110, 113, 114, 162, 224, 225, 230, 231, and 235, (2) positions 53, 61, 68, 74, 76, 80, 130, 137, 194, 195, 198, 200, 204, 205, 209, 210, 253, and 254, and (3) positions 46, 83, 84, 87, 90, 91, 116, 117, 120, 124, 139, 142, 143, 146, 173, 214, 216, 217, 238, 242, and 245, an amino acid residue different from that in the first amino acid sequence, and that has channel activity.