Recombinant Plasmid miRNA Composition for Immune Checkpoint Control
Find Innovative SolutionsGenerate Solutions
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.
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, administered to upregulate miRNA production within cells, thereby decreasing the translation or production of these molecules.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If immune checkpoint molecules are overexpressed to enhance immune response, then immune activity is improved, but homeostasis is disrupted leading to disease
Solution Approach 1:
The patent employs feedback control through miRNA-mediated negative regulation of checkpoint molecule expression. When checkpoint molecules are overexpressed, the miRNA composition detects this increase and responds by degrading their mRNA, thereby reducing expression levels back toward homeostatic balance. This creates a self-regulating system that maintains immune function while preventing pathological overexpression.
Solution Approach 2:
The patent changes the expression parameter of checkpoint molecules from uncontrolled overexpression to regulated expression levels. By introducing miRNA compositions that specifically target checkpoint molecule mRNA, the system dynamically adjusts expression parameters to maintain homeostasis while preserving necessary immune response capabilities.
2Stability of the object's composition
If checkpoint molecule expression is suppressed to restore homeostasis, then disease is treated, but immune response may be compromised
Solution Approach 1:
The patent applies partial suppression of checkpoint molecule expression rather than complete elimination. The miRNA composition reduces expression to therapeutic levels sufficient to treat disease while preserving baseline expression needed for normal immune function. This partial action maintains the balance between treating overexpression and preserving immune response.
3Quantity of substance
If miRNA production is upregulated to degrade target mRNA, then checkpoint molecule bioavailability decreases, but cellular resource consumption increases
Solution Approach 1:
The miRNA composition is designed to be self-amplifying through endogenous production mechanisms. Once introduced, the system leverages cellular transcription and processing machinery to generate miRNA molecules, reducing the need for continuous external administration. The system serves itself by utilizing existing cellular resources efficiently rather than requiring constant external input.
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 suppress the bioavailability of immune checkpoint molecules, restoring homeostasis and potentially treating associated diseases by increasing miRNA production to degrade or inactivate their mRNA.
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.