DNase I-Fc Fusion Plasmids for Increased Biomolecule Bioavailability
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Solution Overview
Problem
Dysregulation of bioactive molecules leads to homeostatic imbalance and disease, necessitating therapies to regulate their expression and production.
Innovation Solution
Compositions comprising recombinant plasmids encoding nucleotide sequences that upregulate the production of mRNA for target biomolecules like TLR3-Fc, TLR9-Fc, DNAse I-Fc, NGF-Fc, or insulin-Fc, administered via vectors such as AAV, protein coats, or lipid vesicles to increase endogenous production in subjects.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If bioactive molecules are over-expressed, then the therapeutic effect is improved, but homeostatic imbalance and disease occur
Solution Approach 1:
The patent employs inducible promoter systems that allow dynamic control of gene expression parameters. The promoter can be switched between active and inactive states based on specific physiological conditions or external inducers, enabling precise adjustment of biomolecule production levels to match therapeutic needs while avoiding harmful over-expression
Solution Approach 2:
The patent implements feedback control mechanisms where the expression of the target biomolecule is regulated based on endogenous signals or external monitoring. This allows the system to automatically adjust production levels, increasing them when therapeutic effect is needed and reducing them when homeostasis is restored, thereby preventing the harmful effects of uncontrolled over-expression
2Productivity
If bioactive molecules are under-expressed, then homeostatic imbalance and disease occur, but increasing expression may cause harmful effects
Solution Approach 1:
The patent uses targeted delivery systems that pre-position the gene expression machinery specifically at the disease site before activation. This ensures that increased biomolecule production occurs only where needed therapeutically, avoiding harmful effects in healthy tissues. The system is activated only after proper positioning and targeting confirmation
Solution Approach 2:
The patent employs tissue-specific or cell-specific promoters that restrict biomolecule expression to particular anatomical locations or cell types. This localizes the therapeutic effect to the affected area while leaving other tissues unaffected, thereby increasing productivity where needed without generating harmful systemic effects
3Quantity of substance
If plasmid encoding is used to upregulate mRNA production, then bioavailability of target biomolecule increases, but complexity of the composition increases
Solution Approach 1:
The patent employs universal promoter elements and regulatory sequences that can control expression of different target genes using the same basic plasmid architecture. This multi-functional design reduces overall system complexity by using standardized components that can be applied across multiple therapeutic targets while maintaining high biomolecule production
Solution Approach 2:
The patent combines multiple functional elements (promoter, enhancer, terminator, selection markers) into a single integrated plasmid construct. This consolidation reduces the number of separate components needed, simplifying the overall composition while maintaining the ability to achieve high levels of mRNA and biomolecule production
Data Source
AI summary
Some embodiments of the present disclosure relate to one or more compositions that upregulate the production of one or more sequences of mRNA. The sequences of mRNA may encode for translation of a target biomolecule, thereby causing an increase in bioavailability of the target biomolecule within a subject that is administered the one or more compositions. In some embodiments of the present disclosure, the target biomolecule is a fusion protein with an Fc fragment, such as a toll-like receptor 3-Fc (TLR3-Fc). In some embodiments of the present disclosure, the target biomolecule is toll-like receptor 9-Fc (TLR9-Fc). In some embodiments of the present disclosure, the target biomolecule is deoxyribonuclease I-Fc (DNAse I-Fc). In some embodiments of the present disclosure, the target biomolecule is neural growth factor-Fc (NGF-Fc). In some embodiments of the present disclosure, the target biomolecule is insulin-Fc.