Recombinant Plasmid miRNA Composition for Immune Checkpoint Downregulation
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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 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 cancer treatment efficacy is improved, but homeostasis is disrupted and disease progresses
Solution Approach 1:
Instead of increasing immune checkpoint molecule expression to enhance immune response, the patent applies the inverse approach by using miRNA to degrade the mRNA of these molecules, thereby reducing their protein production. This inversion resolves the contradiction by eliminating the harmful overexpression while preserving the beneficial immune response through alternative mechanisms.
Solution Approach 2:
The patent introduces miRNA as an intermediary substance that mediates the regulation of immune checkpoint molecules. The miRNA does not directly activate or deactivate the immune response but rather controls the production level of checkpoint molecules by degrading their mRNA, thus restoring homeostasis while maintaining immune efficacy.
2Quantity of substance
If miRNA production is increased to degrade target mRNA, then bioavailability of target biomolecule decreases, but production cost and complexity increase
Solution Approach 1:
The patent employs self-service by utilizing the cell's own transcription and translation machinery to produce the desired miRNA. The miRNA expression vector is integrated into the cell genome, and the cell's endogenous enzymes and ribosomes perform the transcription and translation processes, eliminating the need for external intervention or complex delivery systems.
Solution Approach 2:
The patent applies parameter changes by modifying the genetic code parameters through the use of specific miRNA sequences and expression vectors. By changing the nucleotide sequence parameters and regulating promoter activity, the system achieves controlled miRNA production without increasing overall system complexity.
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 related diseases by enhancing miRNA production within cells.
Implementation Method 1
The sequences of miRNA may be complementary 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 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.