Chimeric Rhodopsin Therapy for Retinal Disease Progression Control
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Solution Overview
Problem
Current treatments for retinal diseases such as retinitis pigmentosa are ineffective in preventing or slowing the progression of the disease, and there is a need for improvements in visual cognitive behavioral functions and visual acuity.
Innovation Solution
A chimeric protein composed of an ion-transporting rhodopsin and a G protein-coupled receptor rhodopsin is administered to prevent or suppress the progression of retinal diseases, improve visual cognitive behavioral functions, and enhance visual functions, such as light-dark determination, bright spot evading, and visual acuity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current treatments for retinal diseases are used, then existing therapeutic approaches are maintained, but they are ineffective in preventing or slowing disease progression
Solution Approach 1:
The patent creates a chimeric protein by combining two different rhodopsin types (ion-transporting rhodopsin from cyanobacteria and G protein-coupled receptor rhodopsin from mammals) into a single functional protein. This composite structure integrates the ion-transport capability of microbial rhodopsin with the signal transduction ability of mammalian rhodopsin, producing a therapeutic agent that effectively suppresses retinal disease progression while maintaining visual functions.
2Ease of operation
If a chimeric protein is administered, then visual cognitive behavioral functions are improved, but the complexity of the therapeutic composition increases
Solution Approach 1:
The chimeric protein is constructed by segmenting and recombining specific functional domains from two different rhodopsin molecules. The ion-transporting rhodopsin portion provides light-driven ion transport capability, while the G protein-coupled receptor rhodopsin portion provides G protein activation capability. This segmentation allows each domain to contribute its specialized function to the overall therapeutic effect.
Solution Approach 2:
The patent merges two distinct rhodopsin molecules into a single chimeric protein structure. This combining of microbial and mammalian rhodopsin sequences creates a unified therapeutic agent that can simultaneously perform ion transport and G protein coupling functions, improving visual cognitive behavioral functions through a single administered composition.
3Reliability
If the chimeric protein is designed with specific amino acid substitutions, then biological activity is optimized, but the manufacturing precision requirements increase
Solution Approach 1:
The patent optimizes the biological activity of the chimeric protein by making specific parameter changes at the amino acid level. Key substitutions include replacing glutamic acid with glutamine at position 132, and modifying residues in the second and third cytoplasmic loops to enhance G protein coupling efficiency. These targeted parameter changes optimize ion transport and signal transduction functions while maintaining manufacturability.
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 chimeric protein effectively suppresses the progression of retinal diseases, enhances visual cognitive behavioral functions, and improves visual acuity by administering a nucleic acid encoding the chimeric protein.
Implementation Method 1
Rhodopsin is a photosensitive receptor with a seven-time-transmembrane structure in the retina of humans and animals
Implementation Method 2
a chimeric protein of two types of rhodopsins, an ion-transporting rhodopsin and a G protein-coupled receptor rhodopsin
Data Source
AI summary
Provided are a chimeric protein of two types of rhodopsins, an ion-transporting rhodopsin and a G protein-coupled receptor rhodopsin, and a nucleic acid encoding the same, for the prevention and suppression of progression of retinal diseases, the improvement in visual cognitive behavioral functions (e.g., improvement in light-dark determination functions, improvement in bright spot evading functions, and/or crisis avoidance functions), and the enhancement of visual functions (e.g., improvement in visual acuity). The present invention also provides a method for preventing or suppressing the progression of a disease, disorder or symptom of the retina, for improving a visual cognitive behavioral function (e.g., improvement in light-dark determination functions, improvement in bright spot evading functions, and/or crisis avoidance functions), or for enhancing visual functions (e.g., improvement in visual acuity), in a subject, where the method comprises the step of administering an effective amount of a nucleic acid encoding a chimeric protein of an ion-transporting receptor rhodopsin and a G protein-coupled receptor rhodopsin to the subject.