Multi-mutated rAAV Capsids for Vascular Endothelial Targeting

The patent applies local quality by creating capsid variants with specific amino acid mutations (e.g., Y500F, Y730F, T491V) that are tailored to enhance binding affinity and transduction efficiency specifically for vascular endothelial cells, while maintaining the ability to infect other cell types. The mutations are strategically placed at specific locations on the capsid surface to optimize interaction with VEC receptors without compromising overall tropism.

The patent employs parameter changes by systematically mutating amino acid residues in the capsid protein sequence (e.g., changing tyrosine to phenylalanine at positions 500 and 730, threonine to valine at position 491) to alter the physical-chemical properties of the capsid surface. These parameter changes in the capsid structure directly improve transduction efficiency in vascular endothelial cells while preserving broad cell type infectivity.

The patent applies segmentation by dividing the capsid protein into distinct functional domains and identifying specific mutation sites (e.g., Y500F, Y730F, T491V) that can be independently modified. This segmented approach allows systematic optimization of VEC targeting through controlled mutations at specific locations rather than random comprehensive changes, reducing the complexity burden.

The patent demonstrates universality by developing capsid variants that simultaneously achieve multiple functions: enhanced VEC targeting specificity, maintained broad cell type infectivity, and improved transduction efficiency. The multi-functional capsid design incorporates several mutations that work together to achieve these overlapping objectives without requiring completely separate vector systems for each function.