miRNA Plasmid Composition for Immune Checkpoint Downregulation
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Bioactive molecules such as immune checkpoint molecules are often overexpressed or misexpressed, leading to homeostatic imbalance and associated diseases, necessitating therapies to regulate their production and function.
Innovation Solution
Compositions comprising recombinant plasmids encoding miRNA sequences that target and degrade the mRNA of immune checkpoint molecules like PD-1, PD-L1, PD-L2, CTLA4, or IDO1, increasing endogenous production of miRNA to downregulate 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 homeostatic balance is lost 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 administered miRNA sequences bind to their mRNA targets and suppress translation, creating a feedback loop that restores homeostatic balance while maintaining necessary immune protection levels
Solution Approach 2:
The patent changes the expression parameter of checkpoint molecules by introducing miRNA sequences that specifically target and downregulate these molecules. This parameter change allows precise control over checkpoint molecule levels, enabling maintenance of protective immunity while preventing pathological overexpression
2Object-affected harmful factors
If checkpoint molecules are suppressed to restore homeostasis, then disease prevention is improved, but immune response may be insufficient
Solution Approach 1:
The patent applies local quality control by using miRNA sequences that specifically target only pathological overexpression of checkpoint molecules rather than suppressing all expression uniformly. This allows selective suppression of harmful overexpression while preserving necessary baseline immune response functionality
Solution Approach 2:
The patent uses partial action by administering miRNA sequences that partially downregulate checkpoint molecules rather than complete suppression. This partial action is sufficient to restore homeostasis and prevent disease while maintaining adequate immune response levels
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 associated diseases by restoring homeostasis and modulating immune responses.
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 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.