Lin28/let-7 Axis Manipulation for Organogenesis Reactivation

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Solution Overview

Problem

Premature birth and intrauterine growth restriction lead to complications such as infection, acute intestinal inflammation, acute and chronic lung disease, and low nephron endowment, with current treatments like dexamethasone causing side effects and not effectively addressing the underlying developmental issues of organogenesis.

Innovation Solution

Manipulating the Lin28/let-7 axis by increasing the expression or activity of Lin28A and/or Lin28B, and inhibiting the expression or activity of let-7 microRNAs, using agents like antagomirs, to prolong or reactivate organogenesis in embryonic organs, thereby increasing the number of progenitor cells that differentiate into functional units.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Speed

If dexamethasone is administered to speed up lung and kidney development in premature infants, then organ maturation is accelerated, but harmful side effects occur

Engineering Contradiction:

Improveorgan maturation speedVSAvoidside effects

Core Design Contradiction:

SpeedVSObject-affected harmful factors

Solution Approach 1:

The patent changes the biological parameters by manipulating the Lin28/let-7 axis to accelerate organ maturation through endogenous pathways rather than exogenous steroid administration, thereby achieving organ maturation acceleration without the harmful side effects of dexamethasone

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent introduces Lin28 and let-7 microRNA as intermediary molecules that mediate the maturation process, replacing the direct steroid hormone pathway with an endogenous microRNA-based regulatory system that achieves the same developmental acceleration without toxic effects

Inventive Principle:

Principle #24Intermediary (Mediator)

2Quantity of substance

If organogenesis is prolonged or reactivated to increase functional nephron number, then kidney function is improved, but the natural developmental timeline is extended

Engineering Contradiction:

Improvenumber of functional nephronsVSAvoidorganogenesis period

Core Design Contradiction:

Quantity of substanceVSDuration of action of moving object

Solution Approach 1:

The patent applies preliminary action by administering Lin28 or let-7 inhibitors during the critical window of nephrogenesis to preemptively expand the pool of progenitor cells before they naturally differentiate and deplete, thereby increasing the final nephron number without extending the overall developmental timeline beyond the natural organogenesis period

Inventive Principle:

Principle #10Preliminary action

Data Source

PatentUS11512316B2Enhanced organogenesis through manipulation of LIN28/LET-7/DIS3L2

Publication Date: 2022.11.29 CHILDRENS MEDICAL CENT CORP

AI summary

Described herein are methods of prolonging or reactivating organogenesis in a subject in need thereof (e.g., a subject that has impaired organ function such as a prematurely born infant). The methods comprise increasing the expression or activity of Lin28A or Lin28B proteins, inhibiting the expression or activity of let-7 family microRNAs, and/or inhibiting the expression or activity of Dis3L2 exonuclease.