Engineered Invasin Polypeptides for Oral Antigen Delivery
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Wild-type Invasin molecules exhibit limited transit efficiency across the gut epithelium, hindering their clinical development for oral delivery of therapeutic agents and vaccines, as they have low integrin binding affinity and specificity.
Innovation Solution
Development of recombinant Invasin polypeptides with specific amino acid substitutions, such as the 909RGD911 motif, which significantly enhance integrin binding affinity and specificity, allowing for improved uptake by intestinal M cells and delivery of therapeutic agents across the gastrointestinal membrane.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If wild-type Invasin molecules are used for oral delivery, then the structure is simple and easy to produce, but the integrin binding affinity and transit efficiency are low
Solution Approach 1:
The patent applies parameter changes by modifying specific amino acid residues in the Invasin polypeptide sequence. The RGD motif (Arginine-Glycine-Aspartic acid) is introduced at positions 909-911, and additional substitutions are made at positions 844, 878, and 885. These parameter changes in the molecular structure dramatically enhance integrin binding affinity while maintaining the polypeptide's overall structure and producibility
Solution Approach 2:
The patent creates a composite polypeptide structure by combining the native Invasin scaffold with engineered RGD motifs and additional amino acid substitutions. This composite approach integrates the natural Invasin structure with optimized binding domains, achieving high integrin affinity while preserving the molecule's fundamental properties for oral delivery
2Productivity
If wild-type Invasin is used, then the molecule maintains natural structure, but the transit efficiency across gut epithelium is limited
Solution Approach 1:
The patent improves transit efficiency by changing key parameters in the Invasin sequence. The introduction of the RGD motif at positions 909-911 and substitutions at positions 844, 878, and 885 create high-affinity binding to intestinal M cell integrins, dramatically enhancing the molecule's ability to traverse the gut epithelium and deliver therapeutic cargo
3Reliability
If Invasin variants with enhanced integrin binding are developed, then binding affinity increases up to 1000-fold, but the polypeptide requires recombinant production with specific mutations
Solution Approach 1:
The patent achieves high integrin binding affinity through targeted parameter changes in the polypeptide sequence. By introducing the RGD motif at positions 909-911 and making specific substitutions at positions 844, 878, and 885, the molecule attains up to 1000-fold increased binding affinity. Despite these modifications, the polypeptide remains producible through standard recombinant DNA techniques in bacterial expression systems
Solution Approach 2:
The engineered Invasin variants are designed to self-assemble and self-fold into their functional conformation when expressed recombinantly. The molecule's native scaffold and engineered domains work together autonomously to create high-affinity integrin binding without requiring complex post-translational modifications or assembly processes, simplifying manufacturing
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
The modified Invasin variants demonstrate increased integrin binding affinity by up to 1000-fold, leading to enhanced transit efficiency and altered cell type specificity, enabling more effective delivery of antigens and therapeutic agents to intestinal immune cells, thereby improving immune responses and protection against gastrointestinal diseases.
Implementation Method 1
Interaction of Invasin-decorated bacteria and other particles with the α5β1 integrin triggers integrin clustering, followed by rapid uptake into M cells
Data Source
AI summary
Recombinant high affinity Invasin polypeptide are provided herein. Further provided are methods of delivering therapeutics such as vaccines by conjugation to the engineered recombinant Invasin polypeptides.