Variant AAV Capsids for Retinal and Choroid/RPE Transduction
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Solution Overview
Problem
Existing adeno-associated dependoparvoviruses (AAVs) face challenges in achieving efficient ocular transduction, particularly in delivering payloads to specific ocular tissues such as the retina and choroid/RPE layers.
Innovation Solution
Development of variant dependoparvovirus capsid proteins, including specific mutations and insertions at defined positions, to enhance the transduction efficiency of AAVs in ocular tissues.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If wild-type AAV capsid proteins are used, then the viral particle can be produced, but the ocular transduction efficiency is insufficient
Solution Approach 1:
The patent applies parameter changes by modifying specific amino acid residues in the capsid protein sequence (e.g., positions 447, 449, 450, 452-461, 586-588, 597-600, 616) to alter the capsid's interaction with ocular tissues. These sequence variations enable the viral particles to achieve enhanced transduction efficiency in retinal and choroid/RPE layers compared to wild-type AAVs
Solution Approach 2:
The invention implements local quality by introducing specific mutations at defined positions within the capsid protein structure. These localized changes (such as insertions between positions 586-588 or substitutions at position 616) confer specialized properties to specific regions of the capsid, enabling targeted interaction with ocular tissue receptors while maintaining overall capsid integrity
2Productivity
If capsid protein sequence is modified to enhance transduction, then ocular delivery capability improves, but capsid structure and stability may be affected
Solution Approach 1:
The patent applies local quality by introducing specific mutations at defined positions within the capsid protein structure. These localized changes (such as insertions between positions 586-588 or substitutions at position 616) confer specialized properties to specific regions of the capsid, enabling targeted interaction with ocular tissue receptors while maintaining overall capsid integrity
Solution Approach 2:
The invention uses parameter changes by systematically varying amino acid sequences at specific positions to optimize the balance between transduction efficiency and structural stability. The selected mutations are designed to minimize disruption to the overall capsid fold while maximizing interaction with ocular tissues
Data Source
AI summary
The disclosure is directed in part to variant capsid polypeptides that can be used to deliver payloads.