Mutant CoChR Polypeptides for Enhanced Light Sensitivity
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Solution Overview
Problem
There is a long-felt need for compositions and methods that restore photosensitivity of the retina in subjects experiencing vision loss, as photoreceptor loss or degeneration severely compromises phototransduction and leads to diminished visual acuity and blindness.
Innovation Solution
The development of isolated light-activated ion channel polypeptides with specific amino acid modifications, such as the mutant CoChR polypeptides, which require less light for activation than wild-type CoChR, thereby enhancing ion and proton flux when expressed in cell membranes and exposed to activating light.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Illumination intensity
If wild-type CoChR is used, then the channel is activated by standard light intensities, but the light sensitivity is insufficient for restoring vision in subjects with photoreceptor loss
Solution Approach 1:
The patent applies parameter changes by introducing specific amino acid mutations (e.g., L112C, T139C, T145A/S146A) into the CoChR protein sequence to alter its photophysical properties. These mutations modify the channel's light absorption characteristics and activation threshold, enabling it to function at lower light intensities and thereby restoring photosensitivity in subjects with vision loss.
2Productivity
If mutant CoChR polypeptides are expressed in cell membranes, then ion flux and proton flux increase, but the complexity of gene delivery and expression systems increases
Solution Approach 1:
The patent employs copying by using viral vectors (such as adeno-associated viruses) to deliver the mutated CoChop gene sequence into target cells. This allows the mutant protein to be produced and expressed within the cell membrane, enabling increased ion flux and proton flux without requiring direct manipulation of the cells themselves.
3Reliability
If photoreceptor cells are lost or degenerated, then visual acuity and light sensitivity are compromised, but restoring native photoreceptor function is not currently possible
Solution Approach 1:
The patent introduces an intermediary approach by expressing the mutant CoChR protein in non-photoreceptor cells (such as retinal ganglion cells or Müller glia) that can still be delivered to the retina. These intermediary cells express the light-sensitive channel and transmit visual signals, effectively bypassing the need for functional photoreceptors and enabling vision restoration in subjects with photoreceptor degeneration.
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 mutant CoChR polypeptides achieve greater light sensitivity and ion flux compared to wild-type CoChR, allowing for improved phototransduction and potential restoration of vision in subjects with vision loss.
Implementation Method 1
Photoreceptors are highly specialized neurons that are responsible for phototransduction, or the conversion of light (in the form of electromagnetic radiation) into electrical and chemical signals
Data Source
AI summary
The invention provides compositions and kits including at least one nucleic acid or polypeptide molecule encoding for a mutant CoChop protein. Methods of the invention include administering a composition comprising a mutant CoChop to a subject to preserve, improve, or restore phototransduction. Preferably, the compositions and methods of the invention are provided to a subject having impaired vision, thereby restoring vision to normal levels.