In Vivo FOXP3 mRNA T-Cell Engineering for Reversible Treg Targeting

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Solution Overview

Problem

Current techniques for utilizing regulatory T-cells (Tregs) in treating inflammatory diseases are not titratable, reversible, and lack targeted administration, limiting their use in critical conditions like sepsis and stroke.

Innovation Solution

In vivo mRNA-based cell engineering using nucleoside modified nucleic acid molecules to convert circulating immune cells into Tregs, combined with targeted delivery of FOXP3 and potentially Helios, and a CAR to enhance anti-inflammatory responses at specific tissue sites.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If systemic administration of IL-2 or ex vivo engineering of Tregs is used, then Treg expansion is achieved, but the technique is not titratable and not reversible

Engineering Contradiction:

ImproveTreg expansionVSAvoidtitratability and reversibility

Core Design Contradiction:

Quantity of substanceVSAdaptability or versatility

Solution Approach 1:

The patent uses in vivo mRNA-based cell engineering to convert circulating immune cells into Tregs, allowing titratable control through adjustable mRNA dosing and reversible effects as the mRNA degrades naturally, eliminating the need for permanent genetic modification

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent replaces the mechanical/ex vivo cell engineering system with an in vivo molecular system using nucleoside modified nucleic acid molecules to achieve Treg conversion, enabling finer control and reversibility through molecular degradation pathways

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

2Quantity of substance

If crude techniques for Treg administration are used, then Treg therapy is achieved, but targeted administration is lacking

Engineering Contradiction:

ImproveTreg administrationVSAvoidtargeted administration

Core Design Contradiction:

Quantity of substanceVSManufacturing precision

Solution Approach 1:

The patent introduces Chimeric Antigen Receptors (CARs) as intermediary molecules that enable Tregs to specifically recognize and target distinct inflammatory sites, providing precise spatial targeting without affecting other tissues

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent creates Tregs with localized functionality by equipping them with CARs that direct their anti-inflammatory activity specifically to sites expressing the target antigen, such as injured myocardial tissue, rather than systemically

Inventive Principle:

Principle #3Local quality

3Force

If endogenous Tregs home to areas of inflammation, then Tregs reach the tissue, but they may not activate to exert anti-inflammatory control

Engineering Contradiction:

ImproveTreg homing capabilityVSAvoidactivation and anti-inflammatory control

Core Design Contradiction:

ForceVSReliability

Solution Approach 1:

The patent performs preliminary action by pre-equipping Tregs with CARs before they encounter the inflammatory site, ensuring they are primed and ready to immediately activate and exert anti-inflammatory control upon encountering their target antigen

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The CAR system provides feedback mechanisms where Treg activation is directly coupled to recognition of the target antigen at the inflammatory site, ensuring activation only occurs when and where needed for precise anti-inflammatory control

Inventive Principle:

Principle #23Feedback

Data Source

PatentUS20250382341A1Methods and compositions of in vivo engineering of t-cells to Anti-inflammatory cells and therapeutic applications there of

Publication Date: 2025.12.18 RGT UNIV OF CALIFORNIA

AI summary

Compositions comprising at least one nanoparticle containing a nucleoside RNA molecule encoding FOXP3 and an optional second agent are described herein. In some cases, the RNA molecule is circular and contains one or more IRES. Methods for treating or preventing inflammation are also described herein.