Mutated Dependoparvovirus Capsids for CNS Transduction
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Solution Overview
Problem
Existing dependoparvovirus vectors, such as adeno-associated viruses (AAVs), face challenges in achieving efficient central nervous system (CNS) biodistribution and transduction.
Innovation Solution
Development of capsid polypeptides with specific mutations, such as A472S, V473A, S483F, and T492S, to enhance the CNS targeting and transduction efficiency of dependoparvovirus particles.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing dependoparvovirus vectors are used, then the vectors can deliver payloads to cells, but the CNS biodistribution and transduction efficiency are insufficient
Solution Approach 1:
The patent applies parameter changes by introducing specific amino acid mutations (A472S, V473A, S483F, T492S) in the capsid polypeptide sequence to alter the physical-chemical properties of the viral capsid surface. These mutations change the interaction parameters between the virus and CNS cells, thereby improving CNS biodistribution and transduction efficiency while maintaining payload delivery capability
Solution Approach 2:
The patent applies local quality by making targeted mutations at specific positions (A472, V473, S483, T492) within the capsid polypeptide rather than uniform modifications. This localized approach optimizes the interaction between the viral capsid and CNS target cells at critical interface regions, enhancing transduction efficiency without compromising overall viral structure and function
Data Source
AI summary
The disclosure is directed in part to dependoparvovirus capsid polypeptides that can be used to deliver payloads.