Engineered Lipid A Molecules for Controlled Immune Activation

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Solution Overview

Problem

Conventional lipid A molecules from Escherichia coli are too potent for immune system modulation in humans, leading to severe side effects, and lack the ability to be used in vaccines or as vaccine adjuvants due to strong immune activation.

Innovation Solution

Engineered lipid A molecules from Moritella genus bacteria, which can be immunostimulatory, weakly immunostimulatory, or immune-silent, allowing for modulation of the immune response by varying the number of C16 acyl chains, and can be used in vaccines or as drug delivery agents without inducing an appreciable immune response.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional lipid A molecules from E. coli are used, then immune system activation is strong, but severe side effects occur and they cannot be used in vaccines

Engineering Contradiction:

Improveimmune system activationVSAvoidside effects

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent modifies the chemical structure of lipid A by changing the length of acyl chains (from typical C16 in E. coli to C12-C14 in Moritella) and the number of acyl chains (5-7 chains). These parameter changes reduce the potency of immune activation to a controllable level that eliminates severe side effects while maintaining immunostimulatory or immune-silent properties depending on the specific configuration.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The invention creates different local configurations of acyl chains on the lipid A molecule. Specifically, it controls the distribution and length of individual acyl chains (some C12, some C14, some C16) to achieve different immunological profiles. This local structural variation allows precise tuning of immune activation levels, producing immunostimulatory, weakly immunostimulatory, or immune-silent variants.

Inventive Principle:

Principle #3Local quality

2Reliability

If conventional lipid A molecules are used, then immune activation is strong, but they lack adaptability for different vaccine applications

Engineering Contradiction:

Improveimmune activationVSAvoidapplicability in vaccines

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent creates a dynamic system where the immunological activity of lipid A can be precisely tuned by adjusting structural parameters. By varying the number of acyl chains (5-7) and their lengths (C12-C16), the invention produces a spectrum of immunological responses from strongly immunostimulatory to completely immune-silent. This dynamic adjustability allows selection of the appropriate lipid A variant for specific vaccine applications, whether strong activation is needed or complete silence is required for drug delivery.

Inventive Principle:

Principle #15Dynamics

3Reliability

If lipid A molecules with C16 acyl chains are reduced, then immune activation decreases, but the ability to form micelles is retained

Engineering Contradiction:

Improveimmune activation levelVSAvoiddrug delivery capability

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent achieves multi-functionality by designing lipid A molecules that can serve different purposes based on their specific configuration. The same basic lipid A structure with modified acyl chains (C12-C14 instead of C16) can function as an immunostimulatory adjuvant when configured for immune activation, or as an immune-silent drug delivery vehicle when configured to avoid immune detection. The ability to form micelles is retained across all variants, enabling drug delivery functionality while the immunological profile is tuned by acyl chain configuration.

Inventive Principle:

Principle #6Universality (Multi-functionality)

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

These engineered lipid A molecules enable controlled immune activation, enhancing vaccine efficacy while minimizing side effects and allowing for drug delivery without immune response, thus providing a safer and more effective immunomodulatory tool.

Implementation Method 1

the lipid A is capable of activating Toll-like receptor signaling, caspase signaling or a combination thereof

Methodology Applied

Scientific EffectToll-like receptor signaling:

Implementation Method 2

the lipid A is capable of activating Toll-like receptor signaling, caspase signaling or a combination thereof

Methodology Applied

Scientific EffectCaspase signaling:

Implementation Method 3

provided herein are lipid A molecules that do not raise a measurable immune response in a subject but retain their ability to naturally form micelles

Methodology Applied

Scientific EffectMicelle formation:

Data Source

PatentUS11878057B2Immunomodulatory lipopolysaccharide compositions

Publication Date: 2024.01.23 CHILDRENS MEDICAL CENT CORP

AI summary

Provided herein are lipid A molecules engineered from Moritella lipopolysaccharides and uses thereof.