Lin-28 Inhibition for miRNA Processing Regulation

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Solution Overview

Problem

Current methods fail to effectively regulate microRNA biogenesis, particularly the processing of pri-miRNA to mature miRNA, which is crucial for cancer treatment due to the involvement of Lin-28 in blocking this process and maintaining cancer stem cells.

Innovation Solution

Inhibiting or activating Lin-28 activity to modulate miRNA biogenesis, either by inhibiting Lin-28 to increase tumor suppressor miRNAs like let-7 or activating it to decrease oncogenic miRNAs, using agents such as siRNA, antibodies, or nucleic acid molecules to target Lin-28 and its variants.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If Lin-28 is active, then cancer stem cells are maintained and miRNA processing is blocked, but tumor suppressor miRNAs cannot be produced effectively

Engineering Contradiction:
Improvecancer stem cell maintenanceVSAvoidtumor suppressor miRNA levels
Core Design Contradiction:
ReliabilityVSQuantity of substance

Solution Approach 1:

The patent extracts and targets Lin-28 protein specifically to remove its inhibitory function on miRNA processing. By using antibodies or other targeting agents against Lin-28, the invention separates the harmful effect (Lin-28 blocking miRNA processing) from the beneficial outcome (production of tumor suppressor miRNAs), thereby resolving the contradiction between maintaining cancer stem cells and producing tumor suppressor miRNAs.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent converts the harmful activity of Lin-28 (which blocks miRNA processing and maintains cancer stem cells) into a beneficial therapeutic target. By developing inhibitors against Lin-28, the invention transforms this harmful factor into a treatable condition, enabling the restoration of normal miRNA processing and the production of tumor suppressor miRNAs that were previously blocked.

Inventive Principle:
Principle #22Blessing in disguise (Convert harm into benefit)

2Stability of the object's composition

If Lin-28 inhibits miRNA processing, then cancer stem cells are maintained, but miRNA biogenesis is blocked

Engineering Contradiction:
Improvecancer stem cell stateVSAvoidmiRNA biogenesis
Core Design Contradiction:
Stability of the object's compositionVSProductivity

Solution Approach 1:

The invention extracts and removes Lin-28 protein from the cellular environment through targeted inhibition. This extraction eliminates the block on miRNA biogenesis while allowing cancer stem cells to lose their self-renewing capability, thereby resolving the contradiction between maintaining stem cell stability and enabling miRNA production.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent introduces intermediary substances (such as antibodies or small molecule inhibitors) that mediate the interaction between therapeutic agents and Lin-28. These intermediaries bind to Lin-28 and prevent its inhibitory function on miRNA processing, thereby restoring miRNA biogenesis without directly affecting cancer stem cell structure.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Reliability

If tumor suppressor miRNAs are increased, then cancer treatment efficacy improves, but current methods cannot effectively regulate miRNA biogenesis

Engineering Contradiction:
Improvecancer treatment efficacyVSAvoidmiRNA biogenesis regulation
Core Design Contradiction:
ReliabilityVSEase of manufacture

Solution Approach 1:

The patent extracts the regulatory function from complex cellular processes and focuses it on a single target: Lin-28 protein. By removing Lin-28 through targeted inhibition, the invention simplifies the regulation of miRNA biogenesis and enables effective production of tumor suppressor miRNAs, thereby improving cancer treatment efficacy while making the process more controllable.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The invention changes the key parameter of Lin-28 activity (from active to inhibited state) to regulate miRNA biogenesis. This parameter change enables the cellular machinery to produce tumor suppressor miRNAs effectively, improving both treatment efficacy and the controllability of the process through well-defined molecular targets.

Inventive Principle:
Principle #35Parameter changes

Data Source

PatentUS8283331B2Methods to regulate miRNA processing by targeting Lin-28
Publication Date: 2012.10.09 CHILDRENS MEDICAL CENT CORP
  • US8283331B2 patent drawing
  • US8283331B2 patent drawing
  • US8283331B2 patent drawing

AI summary

The present invention relates generally to methods to regulate microRNA (miRNA) biogenesis, in particular the regulation of the processing of pri-miRNA to mature miRNA by Lin-28 and/or variants such as Lin28B. In particular, the present invention relates to methods and compositions comprising at least one agent which inhibits Lin-28 function or activity and/or expression to increase the processing of pri-mRNA to mature miRNA. More specifically, one aspect of the invention is directed to treating and/or preventing cancer in a subject by administering an agent that inhibits Lin-28 activity or expression to a subject, preferably a human subject.