Recombinant Plasmid miRNA Control of Immune Checkpoint Expression
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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.
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, 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 anti-tumor activity is improved, but homeostasis is disrupted and disease occurs
Solution Approach 1:
The patent introduces miRNA sequences that provide negative feedback regulation on immune checkpoint molecules. The miRNAs bind to mRNA of checkpoint molecules (PD-1, PD-L1, PD-L2, CTLA4, IDO1) and degrade them, creating a feedback loop that restores homeostasis when checkpoint molecules are overexpressed, thereby treating the disease while maintaining immune response effectiveness
Solution Approach 2:
The patent changes the expression level parameter of immune checkpoint molecules from overexpressed to controlled levels. By introducing miRNA compositions that degrade checkpoint molecule mRNA, the invention adjusts the concentration parameter of these molecules back to physiological ranges, restoring homeostasis without compromising immune function
2Stability of the object's composition
If checkpoint molecules are downregulated to restore homeostasis, then disease is treated, but immune response may be compromised
Solution Approach 1:
The patent employs endogenous miRNA sequences that are naturally produced by the host's immune system. These miRNAs self-regulate checkpoint molecule expression without requiring external intervention, allowing the immune system to restore homeostasis autonomously while maintaining appropriate immune response levels through its own regulatory mechanisms
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 increasing miRNA production to degrade or inactivate their mRNA.
Implementation Method 1
the miRNA can cause the target mRNA to be degraded or inactivated, thereby causing a decrease in bioavailability of the target biomolecule
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 complementary 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.