Circular Non-Viral DNA Vectors for Persistent Low-Immunogenic Expression
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Solution Overview
Problem
Viral gene therapy vectors pose risks such as inflammation, immune response, cytotoxicity, mutagenesis, and carcinogenesis, limiting their clinical use, necessitating the development of safer non-viral alternatives for therapeutic gene delivery.
Innovation Solution
Circular, non-viral DNA vectors are designed with specific structural features, including inverted repeat sequences and a non-repeating nucleotide sequence, to facilitate persistent gene expression and minimize immunogenicity, devoid of CpG sequences and drug resistance genes, and incorporating bacterial origins of replication for efficient delivery.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If viral vectors are used for gene delivery, then delivery efficiency is improved, but safety and immunogenicity worsen
Solution Approach 1:
The patent extracts the harmful viral components while retaining the useful gene delivery function by using non-viral circular DNA vectors. These vectors lack viral genomes and associated immunogenicity, yet maintain efficient delivery capability through alternative mechanisms such as lipid nanoparticle encapsulation and cellular uptake pathways.
Solution Approach 2:
The patent changes the fundamental parameters of the vector structure by using circular non-viral DNA instead of viral genomes. This involves modifying the DNA topology (circular vs linear), removing viral regulatory elements, and adjusting the molecular weight and composition to achieve both safety and efficiency.
2Object-affected harmful factors
If non-viral vectors are used to reduce immunogenicity, then safety is improved, but delivery efficiency worsens
Solution Approach 1:
The patent introduces intermediary delivery systems such as lipid nanoparticles, polymeric carriers, or cellular mechanisms that facilitate the uptake and delivery of non-viral circular DNA vectors. These intermediaries bridge the gap between safety and efficiency by providing a controlled mechanism for cellular entry and gene expression.
Solution Approach 2:
The patent designs multi-functional non-viral vectors that can be delivered through multiple pathways (e.g., lipofection, electroporation, hydrodynamic injection) and express genes in various cell types. This universality allows optimization of delivery efficiency without compromising the inherent safety of non-viral platforms.
3Duration of action of stationary object
If circular DNA vectors with inverted repeats are used, then persistent expression is improved, but vector design complexity worsens
Solution Approach 1:
The patent segments the circular DNA vector into distinct functional modules: inverted repeat sequences that form cruciform structures for persistence, minimal CpG sequences to reduce immunogenicity, and therapeutic gene expression cassettes. This modular segmentation allows independent optimization of each component while simplifying the overall design process.
Data Source
AI summary
The present disclosure relates to circular, non-viral DNA vectors, compositions including one or more of the disclosed vectors, and methods for delivering and/or expressing one or more therapeutic genes (e.g., proteins) in mammals, e.g., human patients. In some embodiments, the present disclosure is directed to circular, non-viral DNA vectors, such as circular non-viral DNA vectors including at least two inverted repeat sequences, where the at least two inverted repeat sequences are separated by a non-repeated nucleotide sequence which is not part of the at least two inverted repeat sequences. In some embodiments, the disclosed circular, non-viral DNA vectors do not include a “DD element.” In some embodiments, the disclosed circular, non-viral DNA vectors do not include a “DD element,” but include at least a portion of a bacterial origin of replication.