MORT RNA Reverses Cell Immortalization

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Solution Overview

Problem

Current methods for immortalizing human mammary epithelial cells often result in gross genomic alterations and passenger errors, making it difficult to identify key participants in breast cancer immortalization, and there is a need for a method to reverse immortalization and detect cancer progression.

Innovation Solution

The development of a method using RNAs and nucleic acids that confer a mortal phenotype, specifically targeting the MORT RNA and its promoter methylation status to reverse immortalization and detect cancer progression, involving liposomes, expression vectors, and pharmaceutical compositions to administer these RNAs and nucleic acids to cells.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Duration of action of stationary object

If current methods are used to immortalize human mammary epithelial cells, then cell immortality is achieved, but gross genomic alterations and passenger errors occur

Engineering Contradiction:
Improvecell lifespanVSAvoidgenomic integrity
Core Design Contradiction:
Duration of action of stationary objectVSManufacturing precision

Solution Approach 1:

The patent extracts and isolates the MORT RNA molecule as a discrete therapeutic agent that can be administered separately from the cell immortalization process. By extracting this specific RNA component, the invention enables reversal of immortalization without requiring to revisit the entire immortalization methodology, thereby addressing genomic integrity issues while maintaining cell lifespan control.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent applies inversion by developing agents and methods that reverse the immortalization process rather than preventing it initially. Instead of trying to immortalize cells without genomic alterations, the invention takes the opposite approach: first allowing immortalization to occur, then using MORT RNA-based agents to reverse it, thereby achieving genomic integrity restoration while maintaining control over cell lifespan.

Inventive Principle:
Principle #13The other way round (Inversion)

2Manufacturing precision

If MORT RNA is targeted to reverse immortalization, then genomic integrity is improved, but detection and quantification complexity increases

Engineering Contradiction:
Improvegenomic integrityVSAvoidMORT RNA quantification
Core Design Contradiction:
Manufacturing precisionVSDifficulty of detecting and measuring

Solution Approach 1:

The patent employs qRT-PCR as an intermediary detection method that converts the complex task of measuring MORT RNA levels into a standardized, quantifiable process. This intermediary technique bridges the gap between the biological molecule (MORT RNA) and the measurement system, enabling accurate quantification through established molecular biology protocols while maintaining sensitivity and specificity.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent utilizes parameter changes in the form of methylation status detection at the MORT promoter region. By monitoring epigenetic modifications (methylation levels) as a proxy for MORT RNA expression, the invention transforms the measurement challenge into a detectable epigenetic parameter that can be assessed through established methylation analysis techniques, thereby simplifying detection while maintaining accuracy.

Inventive Principle:
Principle #35Parameter changes

Data Source

PatentUS10870851B2Non-coding RNAs linked to immortality and associated methods and compositions
Publication Date: 2020.12.22 RGT UNIV OF CALIFORNIA
  • US10870851B2 patent drawing
  • US10870851B2 patent drawing
  • US10870851B2 patent drawing

AI summary

Aspects of the present disclosure include RNAs that confer a mortal phenotype and nucleic acids encoding same. Liposomes, recombinant cells, and pharmaceutical compositions that include the RNAs or nucleic acids encoding same are also provided. Further provided are methods involving quantifying MORT RNAs and/or determining the methylation status of the MORT promoter, as well as methods that employ the RNAs or nucleic acids encoding same.