miR-122* microRNA targeting HPV genes to reduce tumor growth
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current treatments for pre-malignant and malignant conditions, particularly those associated with HPV, are inefficient and carry significant adverse effects, with a need for selective, efficient, and safe therapeutic options that target specific molecular pathways to induce cell death and inhibit tumor growth.
Innovation Solution
The use of miR-122* polynucleotide molecules, capable of specifically affecting gene expression and enhancing p53 tumor suppressor activity, either alone or in combination with siRNA molecules targeting HPV E6 and E7 genes, to induce cell death and inhibit cancer cell growth.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current treatments for pre-malignant and malignant conditions are used, then therapeutic effects are achieved, but significant adverse effects occur
Solution Approach 1:
The invention segments the therapeutic approach by using specific microRNA molecules (miR-122*, miR-34a, miR-200b) that selectively target cancer cells through specific molecular pathways, rather than using broad-spectrum treatments. This segmentation allows therapeutic effects to be achieved while minimizing adverse effects on healthy cells.
Solution Approach 2:
The invention applies local quality by designing microRNA molecules with specific seed sequences that recognize and bind to particular target genes (such as E6, E7 in HPV-associated cancers). This specificity ensures that the therapeutic action is localized to cancer cells expressing these targets, reducing systemic adverse effects.
2Object-affected harmful factors
If selective and efficient therapeutic options targeting specific molecular pathways are developed, then adverse effects are reduced, but treatment complexity increases
Solution Approach 1:
The invention employs microRNA molecules that can target multiple genes involved in cancer pathogenesis simultaneously. For example, certain microRNAs can target both viral oncogenes (E6, E7) and cellular oncogenes (MDM2, RAS), providing multi-functional therapeutic action that reduces the need for multiple separate treatments.
Solution Approach 2:
The microRNA molecules function as self-service therapeutics by autonomously navigating to their target mRNAs, binding to them, and inducing degradation or translational repression without requiring complex delivery systems or external activation mechanisms. The molecules' inherent stability and specificity enable them to perform their therapeutic function independently.
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 introduction of miR-122* leads to significant induction of cell death, reduction in tumor growth, and enhancement of p53 activity, providing a selective and efficient treatment for various cancers, including cervical and hepatic cancers, with potential for reduced adverse effects.
Implementation Method 1
The discovery of RNA interference (siRNA) has enabled selective and highly efficient targeting of specific genes, including genes harbored by disease causing agents. RNA interference entails the introduction of short, double stranded RNA (termed small interfering RNA-siRNA) into cells which results in degradation of defined homologous target gene.
Implementation Method 2
The mature miRNA guides RISC to a target site within mRNAs. If the target site has perfect complementarity to the mature miRNA, the mRNA is cleaved at a position that is located about 10 nucleotides upstream from the 3′ end of the target site.
Implementation Method 3
microRNAs are of about 21 nucleotides in length that are part of a mechanism that regulate posttranscriptional gene expression.
Implementation Method 4
The introduction of miR-122* leads to significant induction of cell death, reduction in tumor growth, and enhancement of p53 activity, providing a selective and efficient treatment for various cancers.
Data Source
AI summary
The present invention provides miR-122* as a functional microRNA molecule, compositions comprising the same and uses thereof for treatment of various conditions, such as, cancer. Further provided are methods for increasing the expression, stability and/or activity of p53 in a target cell or method for inducing cancer cell death, the methods comprising introducing into the cell a miR-122* polynucleotide molecule or a vector expressing or encoding the same.