Mutated mRNA Therapy for Cardiomyocyte Regeneration

Solution Overview

Problem

Current treatments for heart failure, such as heart transplantation and stem cell therapies, are limited by donor availability, rejection risks, and ethical concerns, and there is a need for alternative approaches to enhance cardiomyocyte regeneration in the adult human heart.

Innovation Solution

Locally administering a therapeutic agent containing modified messenger RNAs (mRNAs) that express mutated serum response factor (SRF) and Yes-associated protein (YAP) polypeptides to promote cardiomyocyte regeneration, using a delivery agent like viral transduction vectors or liposomal transfection agents to target diseased heart muscle.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If stem cell therapies are used to repair damaged myocardium, then cardiomyocyte regeneration is improved, but ethical issues, potential teratoma formation, and need for immunosuppression occur

Engineering Contradiction:

Improvecardiomyocyte regenerationVSAvoidethical issues, teratoma formation, immunosuppression

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The invention extracts and applies only the beneficial regenerative capabilities of stem cells by delivering specific transcription factors (YAP and SRF) that induce cardiomyocyte de-differentiation and proliferation, while eliminating the harmful aspects such as teratoma formation and ethical concerns associated with actual stem cell transplantation

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The invention uses modified messenger RNA as an intermediary to deliver transcription factor instructions to adult cardiomyocytes, enabling them to reprogram themselves into a more primitive state without requiring actual stem cell transplantation, thus avoiding the harmful effects of stem cell therapies

Inventive Principle:

Principle #24Intermediary (Mediator)

2Reliability

If heart transplantation is performed for extensive heart failure, then cardiac function is restored, but donor availability is limited and rejection risks increase

Engineering Contradiction:

Improvecardiac function restorationVSAvoiddonor heart availability

Core Design Contradiction:

ReliabilityVSQuantity of substance

Solution Approach 1:

The invention enables the heart to repair itself by delivering modified mRNA that induces endogenous cardiomyocytes to de-differentiate and proliferate, replacing the need for donor hearts and enabling autonomous cardiac regeneration

Inventive Principle:

Principle #25Self-service

Solution Approach 2:

The invention changes the regulatory parameters of adult cardiomyocytes by introducing mutated transcription factors that alter their differentiation state, enabling them to re-enter the cell cycle and proliferate, thus restoring cardiac function without transplantation

Inventive Principle:

Principle #35Parameter changes

3Reliability

If stem cell therapies are used to repair damaged myocardium, then cardiomyocyte regeneration is improved, but rejection risks and immunosuppression requirements increase

Engineering Contradiction:

Improvecardiomyocyte regenerationVSAvoidrejection risks, immunosuppression

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The invention extracts and applies only the beneficial regenerative capabilities of stem cells by delivering specific transcription factors (YAP and SRF) that induce cardiomyocyte de-differentiation and proliferation, while eliminating the harmful aspects such as teratoma formation and ethical concerns associated with actual stem cell transplantation

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The invention uses modified messenger RNA as an intermediary to deliver transcription factor instructions to adult cardiomyocytes, enabling them to reprogram themselves into a more primitive state without requiring actual stem cell transplantation, thus avoiding the harmful effects of stem cell therapies

Inventive Principle:

Principle #24Intermediary (Mediator)

Data Source

PatentUS11179479B2Enhanced cardiomyocyte regeneration

Publication Date: 2021.11.23 ANIMATUS BIOSCIENCES LLC

AI summary

Compositions and methods for promoting adult mammalian cardiomyocytes processes and systems for enhancing cardiomyocyte regeneration are described. The invention relates to locally administering a therapeutic agent containing a modified messenger RNA for expressing a mutated serum response factor polypeptide and a modified messenger RNA for expressing a mutated YAP polypeptide into diseased heart muscle to promote cardiomyocyte proliferation and cardiac regeneration.