Recombinant Plasmid miRNA Composition for Checkpoint mRNA Silencing
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Solution Overview
Problem
Bioactive molecules, such as immune checkpoint molecules, when overexpressed or misexpressed, disrupt homeostasis leading to disease, necessitating therapies to regulate their production and function.
Innovation Solution
Compositions comprising recombinant plasmids that encode miRNA sequences targeting the mRNA of immune checkpoint molecules like PD-1, PD-L1, PD-L2, CTLA4, or IDO1, increasing endogenous production of miRNA to degrade or inactivate these molecules, thereby reducing their bioavailability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If immune checkpoint molecules are overexpressed to enhance immune response, then immune protection is improved, but homeostasis is disrupted leading to disease
Solution Approach 1:
The patent employs miRNA molecules that provide negative feedback regulation by binding to checkpoint molecule mRNA and inhibiting their translation. This feedback mechanism automatically downregulates checkpoint molecules when they are overexpressed, restoring homeostasis while maintaining immune protection functionality.
Solution Approach 2:
The invention changes the expression level parameter of checkpoint molecules by introducing miRNA molecules that specifically target and reduce the translation of checkpoint molecule mRNA, thereby adjusting the biochemical parameter from overexpression to regulated expression levels.
2Stability of the object's composition
If checkpoint molecules are suppressed to restore homeostasis, then disease is treated, but immune protection may be reduced
Solution Approach 1:
The patent uses miRNA molecules that partially suppress checkpoint molecule translation rather than completely eliminating it. This partial action maintains sufficient immune protection while restoring homeostasis, avoiding complete suppression that would compromise immune function.
Solution Approach 2:
The miRNA molecules act as intermediary agents that mediate between the conflicting requirements of immune protection and homeostasis. They provide a controlled mechanism to regulate checkpoint molecules, allowing the system to balance both functions simultaneously.
3Productivity
If recombinant plasmids are used to deliver miRNA sequences, then miRNA production is increased, but delivery complexity increases
Solution Approach 1:
The recombinant plasmids are designed to autonomously express miRNA sequences within host cells without requiring complex external delivery infrastructure. The plasmid system self-replicates and self-expresses, simplifying the overall delivery complexity while maintaining high miRNA production.
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 compositions effectively downregulate immune checkpoint molecules, restoring homeostasis and potentially treating associated diseases by enhancing miRNA production within cells.
Implementation Method 1
The sequences of miRNA may be complimentary to a sequence of target messenger RNA (mRNA) that encodes for translation of a target biomolecule and the miRNA can cause the target mRNA to be degraded or inactivated
Data Source
AI summary
Embodiments of the present disclosure relate to a composition that comprises a recombinant plasmid (RP) with a sequence of nucleic acids. The sequence comprise a start region, an end region and an insert positioned between the start region and the end region. The insert encodes for a sequence of micro interfering ribonucleic acid (miRNA) that may be complimentary to a sequence of target messenger RNA (mRNA) that encodes for translation of a target biomolecule. The miRNA can cause the target mRNA to be degraded or inactivated, thereby causing a decrease in bioavailability of the target biomolecule because it is degraded or inactivated by the miRNA, thereby decreasing the bioavailability of the target biomolecule. In some embodiments of the present disclosure, the target biomolecule is an immune checkpoint protein.