Multimeric Protein Toxins for Targeted Cell Specificity
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Solution Overview
Problem
Current bacterial toxins lack specificity in targeting cell populations, often affecting both target and non-target cells due to reliance on a single characteristic, leading to non-specific toxicity.
Innovation Solution
Development of modified bacterial toxins comprising two different monomers that form a heterooligomer, with modifications such as substitution of native cell-recognition domains and proteolytic activation sites, and mutation of monomers to ensure specific binding and activation only on target cells expressing multiple characteristics.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If bacterial toxins are designed to target specific cell populations, then target cell specificity is improved, but non-specific toxicity to non-target cells increases
Solution Approach 1:
The toxin is divided into separate monomeric subunits that must assemble into a heterooligomer to become active. Each monomer can be independently engineered to recognize different cell surface characteristics, allowing the toxin to require multiple specific features simultaneously for activation, thereby improving target cell specificity while reducing non-specific toxicity.
Solution Approach 2:
Different monomers within the heterooligomer are赋予 different recognition specificities through localized modifications of their binding domains. This allows each monomer to independently recognize a specific cell surface characteristic, and the toxin only becomes active when all required characteristics are present on the target cell.
2Measurement precision
If hetero-oligomeric toxins with multiple monomer types are designed, then target cell specificity is improved, but device complexity increases
Solution Approach 1:
The complex hetero-oligomeric structure is segmented into standardized monomeric building blocks with defined interfaces. Each monomer type can be independently expressed and purified, then self-assemble into the functional heterooligomer, simplifying the overall production and characterization process despite the complexity of the final structure.
Solution Approach 2:
The monomers are designed with universal binding interfaces and oligomerization domains that allow them to function in multiple contexts. The same monomer design principles can be applied to create different heterooligomeric toxins targeting various cell types, reducing the overall complexity of developing multiple toxin variants.
Data Source
AI summary
The present invention provides compositions comprising modified bacterial toxins and methods for using the modified bacterial toxins for targeting particular cell populations and for treating diseases.