Retinal-Targeted AAV2 Capsid Variants for Higher Transduction
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
The development of novel AAV variants with high transduction efficiency into retinal cells is crucial for wider clinical application and is in high demand in the market.
Innovation Solution
A novel AAV variant comprising a capsid variant with specific VP1 amino acid sequences (SEQ ID NOs: 02 to 31) is provided, enhancing delivery efficiency to retinal and RPE tissues.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If wild-type AAV is used for gene delivery, then broad tissue tropism is achieved, but transduction efficiency into retinal cells is insufficient
Solution Approach 1:
The patent applies local quality by introducing specific amino acid substitutions at key positions (e.g., positions 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100) in the VP1 capsid protein sequence. These localized amino acid changes modify specific regions of the capsid to enhance affinity for retinal cell surface receptors, thereby improving transduction efficiency into retinal cells while preserving the overall capsid structure and broad tissue tropism characteristics of wild-type AAV.
2Productivity
If AAV capsid sequence is modified to improve retinal cell transduction, then delivery efficiency to retinal tissue is enhanced, but viral stability may be compromised
Solution Approach 1:
The patent applies parameter changes by systematically modifying amino acid parameters at specific positions in the VP1 capsid protein sequence. The substitutions are carefully selected to change local chemical properties (e.g., hydrophobicity, charge, size) that influence retinal cell binding affinity, while maintaining parameters critical for viral stability such as capsid assembly efficiency, genome packaging, and resistance to neutralizing antibodies. This balanced approach enhances delivery efficiency to retinal tissue while preserving viral stability.
3Adaptability or versatility
If multiple AAV variants are developed for different retinal diseases, then clinical applicability is improved, but development complexity increases
Solution Approach 1:
The patent applies universality by developing a platform of AAV capsid variants based on the AAV2 serotype that can be applied across multiple retinal diseases. The variants share common structural features and assembly mechanisms, allowing a single development framework to serve multiple therapeutic indications including retinitis pigmentosa, macular degeneration, and other inherited retinal disorders. This multi-functional approach improves clinical applicability while managing development complexity through standardized characterization and safety assessment protocols.
Data Source
AI summary
The present disclosure relates to an AAV variant, for example, an AAV2 variant. An AAV variant according to some embodiments of the present disclosure comprises a VP1 variant comprising having any one amino acid sequence selected from SEQ ID NOS: 02 to 31.