Viral Vector Delivery via Modified Poly(beta-amino Ester) Complexes
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Solution Overview
Problem
The lack of safe and efficient vectors for delivering virus-based therapeutic agents in vivo is hindered by high sero-prevalence of antibodies and natural liver tropism, which reduces the circulating dose and therapeutic efficacy, and increases undesirable side-effects.
Innovation Solution
End-modified poly(beta-amino ester)s (PBAEs) are used to form complexes with virus-based therapeutic agents, providing biodegradable and biocompatible delivery vectors that mask the agents from neutralizing antibodies, reduce liver tropism, and enhance tumor targeting, thereby improving circulation time and therapeutic efficiency.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If viral vectors are used for gene therapy delivery, then therapeutic efficacy is improved, but immune recognition and neutralization by antibodies increases
Solution Approach 1:
The patent uses poly(beta-amino ester) polymers as intermediary carriers that bind to viral vectors and form complexes. These polymer coatings act as mediators that protect the viral vectors from neutralizing antibodies while maintaining their ability to deliver therapeutic genes. The polymer layer serves as a protective interface between the immune system and the viral vector.
Solution Approach 2:
The patent modifies the physical and chemical parameters of viral vectors by coating them with polymers of specific molecular weights, compositions, and surface properties. This changes the immunogenicity parameters of the viral vectors, reducing their recognition by the immune system while preserving their therapeutic function.
2Area of stationary object
If viral vectors are administered systemically, then broad tissue coverage is achieved, but liver uptake and clearance increases
Solution Approach 1:
The patent alters the surface properties and physical parameters of viral vectors through polymer coating. This modification changes the biodistribution parameters, reducing preferential uptake by the liver and extending circulation half-life, thereby maintaining higher circulating doses over time.
Solution Approach 2:
The polymer coating acts as an intermediary layer that modifies how viral vectors interact with liver cells and the reticuloendothelial system. This intermediate layer prevents direct recognition and uptake by liver Kupffer cells, allowing broader tissue distribution while reducing hepatic clearance.
3Productivity
If higher dosages of viral vectors are administered, then therapeutic efficiency is improved, but immune activation and side effects increase
Solution Approach 1:
The polymer coating serves as a protective intermediary that allows administration of higher viral vector dosages without proportionally increasing immune activation. The coating layer shields the viral vectors from immune recognition, enabling therapeutic doses to be increased for better efficacy while the polymer barrier prevents corresponding increases in immune responses and side effects.
Data Source
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AI summary
Disclosed are complexes of virus-based therapeutic agents with polymers that are poly(beta-amino ester)s (PBAEs) modified with at least one oligopeptide. Also disclosed are methods of treatment using these complexes and methods of encapsulating said complexes to form nanoparticles.