Plasmid-Based miR Inhibitory System for Long-Term Repression
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Solution Overview
Problem
Current tools for analyzing and inhibiting microRNA (miR) function are expensive, time-consuming, and require repetitive administration, lacking long-term efficacy and safety for cancer and disease treatment.
Innovation Solution
A plasmid-based miR inhibitory system (PMIS) utilizing hairpin structures that enhance the binding of antisense oligos to miRs, incorporating AU-rich flanking sequences to facilitate physical interactions with proteins, allowing for transient or constitutive expression and long-term repression of specific miRs.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If gene targeting mutagenesis or chemically modified miR antagomirs are used to analyze miR function, then miR inhibition can be achieved, but the process becomes expensive and time-consuming
Solution Approach 1:
The patent incorporates miR inhibitor sequences directly into the genome during a preliminary genetic modification step. This allows the cells to produce the inhibitor continuously without requiring repeated administrations of chemically modified antagomirs, thereby reducing both time and cost while maintaining reliable miR inhibition
Solution Approach 2:
The patent creates a genetic copy of the miR inhibitor sequence that is integrated into the host genome. This copied sequence functions as a self-sustaining source of the inhibitor, eliminating the need for continuous external supply of expensive chemically modified oligonucleotides
2Reliability
If chemically modified miR antagomirs are administered repeatedly to maintain miR inhibition, then therapeutic effect can be sustained, but side effects increase and safety decreases
Solution Approach 1:
The genetically modified cells serve themselves by continuously producing the miR inhibitor endogenously. This self-sustaining production mechanism eliminates the need for repeated external administrations that cause side effects, while maintaining sustained therapeutic effect through continuous endogenous synthesis of the inhibitor
3Reliability
If current miR analysis tools are used, then miR function can be studied, but the cost increases significantly
Solution Approach 1:
The patent uses a simple genetic sequence integration approach that replaces expensive chemically modified oligonucleotides. The genetically encoded inhibitor is produced using the cell's own machinery, eliminating the need for costly external reagents and significantly reducing the cost of miR function analysis
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The PMIS effectively reduces target miR levels by 25-90% and is safer with reduced side effects, providing a cost-effective, long-term therapeutic option for various cancers and diseases without the need for frequent reapplication.
Implementation Method 1
antisense oligos to miRs
Implementation Method 2
These structures may coordinate physical interactions with proteins that bring the antisense oligo close to the miR and dramatically facilitate their binding
Data Source
AI summary
The present invention relates to plasmid-based miR inhibitory systems (PMIS), miR inhibitors and methods of use of these systems and inhibitors.