Chimeric Rhodopsin Construct With ER Export Signal for Visual Restoration
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Solution Overview
Problem
Current treatments for retinal diseases and visual impairments, such as retinitis pigmentosa, lack effective methods for preventing disease progression and enhancing visual functions.
Innovation Solution
A nucleic acid construct encoding a chimeric protein comprising an ion-transporting receptor rhodopsin and a G protein-coupled receptor rhodopsin, with an endoplasmic reticulum export signal sequence, is expressed to improve visual cognitive behavioral functions and enhance visual functions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If conventional rhodopsin treatment is used, then visual function restoration is attempted, but gene expression efficiency is low and visual restoration效果 is insufficient
Solution Approach 1:
The patent creates a chimeric rhodopsin protein by combining functional domains from different rhodopsin types (ion-transporting rhodopsin and G protein-coupled receptor rhodopsin) into a single composite protein structure. This composite protein achieves both high expression efficiency and effective visual restoration function that neither parent protein could achieve alone.
Solution Approach 2:
The patent introduces an endoplasmic reticulum export signal sequence at specific location (N-terminus) of the chimeric rhodopsin protein. This localized addition of a specific functional sequence dramatically improves gene expression efficiency by directing proper protein trafficking and folding, without compromising the overall visual restoration function.
2Reliability
If current treatments for retinal diseases are applied, then disease management is attempted, but prevention of disease progression and enhancement of visual functions are insufficient
Solution Approach 1:
The chimeric rhodopsin protein is designed to perform multiple functions simultaneously: it prevents retinal disease progression by replacing defective native rhodopsin, restores visual function by enabling proper phototransduction, and enhances visual sensitivity through optimized ion transport and G protein coupling. This single protein addresses multiple therapeutic needs that conventional treatments could not satisfy simultaneously.
3Productivity
If chimeric rhodopsin without ER export signal is expressed, then protein structure is formed, but expression efficiency is remarkably low
Solution Approach 1:
The endoplasmic reticulum export signal sequence is added to the N-terminus of the chimeric rhodopsin coding sequence before protein expression begins. This preliminary addition of the signal sequence ensures that as soon as the protein is synthesized, it is properly directed to the endoplasmic reticulum for folding and processing, dramatically improving expression efficiency and making clinical production feasible.
Data Source
AI summary
Provided are: a nucleic acid including a nucleic acid sequence encoding a chimeric protein including at least part of an ion-transporting receptor rhodopsin and at least part of a G protein-coupled receptor rhodopsin and a nucleic acid sequence encoding a signal sequence; and a nucleic acid including a nucleic acid sequence encoding a chimeric protein including at least part of an ion channeling receptor rhodopsin and at least part of a G protein-coupled receptor rhodopsin; and a nucleic acid construct including the nucleic acid sequences. The use of the nucleic acids or nucleic acid constructs prevents and suppresses the progress of retinal diseases, and enhances the visual cognitive behavioral function and visual function.