Recombinant Plasmid miRNA Composition for Immune Checkpoint Suppression
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Solution Overview
Problem
Bioactive molecules such as immune checkpoint molecules are often overexpressed or misexpressed, leading to homeostasis disruption and associated diseases.
Innovation Solution
Compositions comprising recombinant plasmids that encode for microRNA (miRNA) sequences are administered to upregulate miRNA production, targeting and degrading or inactivating the mRNA of immune checkpoint molecules like PD-1, PD-L1, PD-L2, CTLA4, or IDO1, thereby reducing their bioavailability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If immune checkpoint molecules are overexpressed or misexpressed, then homeostasis is lost and disease occurs, but suppressing their expression requires interfering with endogenous gene regulation mechanisms
Solution Approach 1:
The patent uses recombinant plasmids containing synthetic miRNA precursor sequences that are copies of natural miRNA structures. These synthetic copies are designed to mimic endogenous miRNA biogenesis pathways, allowing the cell's own machinery to process them into active miRNAs that can then target and suppress checkpoint molecule mRNAs, thereby restoring homeostasis without requiring direct manipulation of complex gene regulation mechanisms
Solution Approach 2:
The patent introduces recombinant plasmids as intermediary carriers that deliver synthetic miRNA precursor sequences into cells. These plasmids act as mediators between the therapeutic goal (suppressing checkpoint molecules) and the cellular machinery (miRNA biogenesis pathway), enabling indirect control of gene expression through the cell's own regulatory systems
2Quantity of substance
If recombinant plasmids encoding miRNA sequences are administered to upregulate miRNA production, then bioavailability of target biomolecule decreases, but this requires precise targeting to avoid off-effect
Solution Approach 1:
The patent designs miRNA precursor sequences with specific local characteristics - the mature miRNA region is engineered to have exact complementarity to the target checkpoint molecule mRNA sequence, while other regions are optimized for processing by cellular enzymes. This local quality differentiation ensures that the miRNA acts precisely on its intended target without affecting other genes, achieving high targeting precision while effectively reducing biomolecule bioavailability
Solution Approach 2:
The recombinant plasmid is segmented into distinct functional regions: a backbone sequence for replication and delivery, and an insert sequence containing the synthetic miRNA precursor. The precursor itself is segmented into regions that will form the mature miRNA and regions that facilitate processing. This segmentation allows independent optimization of each component for both precision and effectiveness
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 decrease the production and bioavailability of immune checkpoint molecules, potentially treating or preventing diseases related to their dysregulation by enhancing endogenous miRNA production.
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.