Viral Vector Encoding ELOVL2 for AMD Treatment

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Solution Overview

Problem

Current treatments for age-related macular degeneration (AMD) lack effective prevention and cure, with existing methods not addressing the underlying biological mechanisms related to ELOVL2 methylation and its impact on retinal health.

Innovation Solution

A viral vector encoding an ELOVL2 protein or polypeptide is administered for ophthalmic use, specifically via parenteral routes to the eye, utilizing Adeno-associated virus delivery to increase ELOVL2 expression, thereby addressing the methylation-related decline in retinal health.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional treatments are used for AMD, then current standard care is provided, but effective prevention and cure are not achieved

Engineering Contradiction:
Improveeffectiveness of AMD treatmentVSAvoidprevention and cure capability
Core Design Contradiction:
ReliabilityVSProductivity

Solution Approach 1:

The patent changes the molecular parameter of ELOVL2 gene methylation status by delivering a viral vector encoding a demethylation agent. This demethylation agent removes methyl groups from the ELOVL2 promoter region, thereby increasing ELOVL2 expression levels. The increased ELOVL2 expression leads to enhanced synthesis of long-chain polyunsaturated fatty acids (VLC-PUFAs), which are critical for retinal health and AMD prevention. This parameter change at the epigenetic level resolves the contradiction by providing a mechanism for both treatment and prevention that conventional therapies cannot achieve.

Inventive Principle:
Principle #35Parameter changes

2Reliability

If ELOVL2 expression is increased to treat AMD, then retinal health improves, but the underlying methylation mechanism must be targeted

Engineering Contradiction:
Improveretinal healthVSAvoidmethylation targeting mechanism
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent introduces a viral vector as an intermediary delivery system that carries and expresses a demethylation agent. This viral vector serves as the mediator between the external administration and the internal methylation modification. The demethylation agent produced by the viral vector then acts as the direct agent to remove methyl groups from the ELOVL2 promoter, thereby increasing ELOVL2 expression. This intermediary approach simplifies the overall mechanism by using a well-established viral vector system to achieve epigenetic modification, avoiding the need for direct complex methylation targeting methods.

Inventive Principle:
Principle #24Intermediary (Mediator)

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

This approach effectively treats AMD by enhancing ELOVL2 expression, improving visual function, and reducing the progression of age-related eye diseases by targeting the methylation status of the ELOVL2 gene.

Implementation Method 1

A viral vector encoding an ELOVL2 protein or polypeptide is administered for ophthalmic use... utilizing Adeno-associated virus delivery to increase ELOVL2 expression

Methodology Applied
Scientific EffectGene expression:

Implementation Method 2

ELOVL2 encodes a transmembrane protein involved in the synthesis of long (C22 and C24) ω3 and ω6 polyunsaturated fatty acids (VLC-PUFA). Specifically, ELOVL2 is capable of converting docosapentaenoic acid (DPA) (22:5n-3) to 24:5n-3, which is the precursor of 22:6n-3, docosahexaenoic acid (DHA)

Methodology Applied
Scientific EffectFatty acid elongation:

Data Source

PatentEP3801465B1Viral vector encoding elovl2 protein for treating age-related macular degeneration
Publication Date: 2024.07.24 RGT UNIV OF CALIFORNIA
  • EP3801465B1 patent drawingFigure 1A~1D
  • EP3801465B1 patent drawingFigure 2A~2C
  • EP3801465B1 patent drawingFigure 3A~3E

AI summary

Methods for treating age-related eye diseases or conditions are provided. Methods for treating an age-related eye disease or condition in a subject by administering one or more demethylation compounds or agents are provided.