AAV Capsid 3D Surface Mapping for Tissue Selectivity
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Solution Overview
Problem
Existing AAV therapeutics face limitations due to low tissue or cell type selectivity, particularly for CNS-related diseases, necessitating the development of AAV capsid variants for targeted delivery to specific organs, tissues, or cell types.
Innovation Solution
Methods are developed to characterize 3D molecular surface features of AAV capsids using DNA encoded libraries (DECLs, DEALs, and phage display libraries) by contacting AAV capsids with aptamer or antibody libraries, removing unbound agents, eluting and identifying bound agents, and determining their presence and level to map the surface features.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If AAV capsid variants are developed for targeted delivery to specific organs, tissues or cell types, then tissue or cell type selectivity is improved, but device complexity increases due to the need for mapping 3D molecular surface features
Solution Approach 1:
The patent employs a universal aptamer library platform that can be applied to characterize any AAV capsid variant. The same library and methodology are used across different capsid types, allowing the system to serve multiple functions: identifying binding epitopes, mapping 3D surface features, and predicting tissue tropism across various AAV serotypes and variants, thereby improving selectivity without proportionally increasing complexity
Solution Approach 2:
The patent creates a digital map or fingerprint of the 3D molecular surface features by identifying and characterizing bound aptamers. This copying of surface feature information into a analyzable format allows researchers to study and compare capsid variants without repeatedly performing complex physical mapping experiments, thus improving selectivity while managing complexity
2Measurement precision
If DNA encoded libraries are used to map 3D molecular surface features, then measurement precision of surface features is improved, but loss of time increases due to multiple steps including contacting, removing unbound, eluting, and identifying
Solution Approach 1:
The patent performs preliminary enrichment of the aptamer library through multiple rounds of binding and elution before final identification. This preliminary action concentrates the relevant binding aptamers, reducing the complexity of subsequent analysis and enabling more precise mapping of 3D surface features. The sequential enrichment steps are optimized to achieve sufficient precision while minimizing total processing time
Solution Approach 2:
The patent replaces traditional time-consuming physical mapping methods (such as X-ray crystallography or cryo-EM) with a biochemical approach using aptamer binding profiles. This substitution allows measurement of 3D surface features through chemical interactions and sequencing, achieving comparable or superior precision while reducing the time required for structural characterization
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
These methods enable the delineation of AAV capsid 3D molecular surface features, facilitating the development of AAV capsid variants with improved tissue and cell type specificity for targeted gene delivery, enhancing therapeutic efficacy.
Implementation Method 1
contacting the AAV capsid with an aptamer library targeting one or more AAV capsids
Data Source
AI summary
Provided are compositions and methods for obtaining and mapping 3D molecular surface features of viral capsids (e.g., AAV capsids).