APC-Targeting Lipid Composition for Spleen-Selective mRNA Delivery

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Solution Overview

Problem

Existing lipid-based delivery systems for mRNA to antigen-presenting cells lack the ability to selectively target these cells while avoiding expression in non-target organs like the liver and lung, leading to potential harmful immune responses and inefficiencies.

Innovation Solution

A lipid composition with a specific molar ratio of permanently anionic, cationic, and neutral lipids, optimized to achieve high expression in antigen-presenting cells, particularly in the spleen, while minimizing expression in other organs, using a ratio of (14 to 33):(40 to 57):(22 to 40) for enhanced targeting specificity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If traditional lipid nanoparticles (LNPs) are used to deliver mRNA, then mRNA delivery efficiency is improved, but organ-targeting specificity deteriorates due to non-selective delivery to liver and lung

Engineering Contradiction:

ImprovemRNA delivery efficiencyVSAvoidorgan-targeting specificity

Core Design Contradiction:

ProductivityVSManufacturing precision

Solution Approach 1:

The patent applies local quality by incorporating a permanently cationic lipid component specifically designed to interact with negatively charged surface molecules on antigen-presenting cells. This creates a localized functional property at the cell surface interaction interface, enabling selective binding to APCs while maintaining overall LNP structure and mRNA delivery capability.

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The patent changes the charge parameter of the lipid composition by incorporating permanently cationic lipids with positive charges that can electrostatically interact with negatively charged APC surface molecules. This parameter change enables selective targeting of APCs through electrostatic attraction, improving organ-targeting specificity while maintaining delivery efficiency.

Inventive Principle:

Principle #35Parameter changes

2Quantity of substance

If mRNA is delivered to non-target organs like liver and lung, then delivery volume is increased, but harmful immune responses are generated

Engineering Contradiction:

ImprovemRNA delivery volumeVSAvoidharmful immune responses

Core Design Contradiction:

Quantity of substanceVSObject-affected harmful factors

Solution Approach 1:

The patent uses permanently cationic lipids as intermediaries that mediate selective interaction between the LNP carrier and antigen-presenting cells. These cationic lipids act as a bridge, enabling specific binding to APCs through electrostatic interaction with negatively charged cell surface molecules, thereby directing mRNA delivery away from non-target organs and preventing harmful immune responses.

Inventive Principle:

Principle #24Intermediary (Mediator)

3Object-affected harmful factors

If ionizable cationic lipids are used in LNPs, then cell toxicity is reduced, but targeting specificity to antigen-presenting cells deteriorates

Engineering Contradiction:

Improvecell toxicityVSAvoidtargeting specificity

Core Design Contradiction:

Object-affected harmful factorsVSManufacturing precision

Solution Approach 1:

The patent employs composite materials by combining ionizable cationic lipids (which reduce toxicity) with permanently cationic lipids (which provide targeting specificity). This composite lipid composition integrates the beneficial properties of both lipid types: the ionizable component minimizes cellular toxicity while the permanently cationic component enables selective binding to negatively charged APC surfaces through persistent electrostatic interaction.

Inventive Principle:

Principle #40Composite materials

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

The composition achieves significantly higher protein expression levels and cell targeting specificity in antigen-presenting cells, enhancing immune responses and reducing expression in non-target organs, thus improving the efficacy of mRNA immunotherapy.

Implementation Method 1

permanently cationic lipid component that interacts with negatively charged cell surface molecules

Methodology Applied

Scientific EffectElectrostatic interaction: Electrostatics

Implementation Method 2

Negatively charged mRNA condenses within the positively charged polymer

Methodology Applied

Scientific EffectElectrostatic interaction: Electrostatics

Data Source

PatentUS12485170B2Lipid composition targeting antigen-presenting cells and use thereof

Publication Date: 2025.12.02 BEIJING YUEKANGKECHUANG PHARM TECH CO LTD

AI summary

The present disclosure relates to the technical field of molecular biology and provides a lipid composition targeting antigen-presenting cells and a use thereof. The composition provided by the present disclosure demonstrates good organ and cell targeting specificity, significantly enhancing the protein expression level of antigens in the spleen. Additionally, the composition significantly increases the percentage of cells that express the antigen among antigen-presenting cells (e.g., B cells, pDC cells, cDC cells, and macrophages) in the spleen, indicating that the composition can be used in the immunotherapy of diseases.