Split Otoferlin Vector Composition for Genetic Hearing Loss
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current treatments for hearing loss, particularly non-syndromic sensorineural hearing loss, lack effective methods for preventing or reversing the condition, with a focus primarily on cochlear hair cell regeneration and amplification devices.
Innovation Solution
A composition comprising two different nucleic acid vectors, each encoding a portion of the otoferlin protein, which undergo concatemerization or homologous recombination in mammalian cells to produce a full-length otoferlin protein, addressing genetic defects associated with non-syndromic sensorineural hearing loss.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If traditional treatments (hearing amplification devices, cochlear implants) are used for hearing loss, then hearing function can be partially restored, but the treatments cannot address the underlying genetic defects and require external devices that do not cure the condition
Solution Approach 1:
The patent replaces mechanical amplification devices with a biological/genetic solution. Instead of using external amplifiers or implants to compensate for hearing loss, the invention introduces functional otoferlin protein via nucleic acid vectors that correct the underlying genetic defect in hair cells, enabling endogenous production of the defective protein and restoring hearing function without external devices.
Solution Approach 2:
The patent uses nucleic acid vectors to copy and introduce the functional otoferlin gene sequence into the patient's cells. The vectors contain DNA sequences that replicate and express the wild-type otoferlin protein, effectively copying the healthy genetic information to replace the defective endogenous genes.
2Ease of operation
If single nucleic acid vector is used to encode otoferlin protein, then delivery is simplified, but the vector cannot accommodate full-length otoferlin coding sequence due to size limitations
Solution Approach 1:
The patent divides the otoferlin coding sequence into multiple segments, each encoded by a separate nucleic acid vector. This segmentation allows each vector to remain within acceptable size limits for efficient delivery and expression, while the combined effect of multiple vectors provides complete functional coverage of the otoferlin protein.
Solution Approach 2:
The patent combines multiple nucleic acid vectors that each encode portions of the otoferlin protein. The vectors are designed to work synergistically, with their encoded sequences complementing each other to produce the full-length functional otoferlin protein through cellular translation mechanisms.
3Reliability
If gene therapy approaches are used to correct genetic defects, then the underlying cause of hearing loss can be addressed, but the treatment complexity and delivery challenges increase
Solution Approach 1:
The patent uses nucleic acid vectors as intermediary carriers to deliver the functional otoferlin gene sequence into target cells. These vectors serve as mediators that facilitate the introduction of genetic material without requiring complex surgical procedures or direct manipulation of the genome, simplifying the delivery process while achieving genetic correction.
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 approach enhances otoferlin protein expression, potentially restoring hearing function in individuals with defective otoferlin genes, offering a novel therapeutic strategy for treating non-syndromic sensorineural hearing loss.
Implementation Method 1
each of the at least two different vectors includes a coding sequence that encodes a different portion of an otoferlin protein... when introduced into a mammalian cell the at least two different vectors undergo concatemerization or homologous recombination with each other, thereby forming a recombined nucleic acid that encodes a full-length otoferlin protein
Implementation Method 2
when introduced into a mammalian cell the at least two different vectors undergo concatemerization or homologous recombination with each other, thereby forming a recombined nucleic acid that encodes a full-length otoferlin protein
Implementation Method 3
when the coding sequences are transcribed in a mammalian cell to produce RNA transcripts, splicing occurs between the splicing donor signal sequence on one transcript and the splicing acceptor signal sequence on the other transcript
Implementation Method 4
when the coding sequences are transcribed in a mammalian cell to produce RNA transcripts, splicing occurs between the splicing donor signal sequence on one transcript and the splicing acceptor signal sequence on the other transcript, thereby forming a recombined RNA molecule that encodes a full-length otoferlin protein
Data Source
AI summary
Provided herein are compositions that include at least two different nucleic acid vectors, where each of the at least two different vectors includes a coding sequence that encodes a different portion of an otoferlin protein, and the use of these compositions to treat hearing loss in a subject.