CD98hc-Targeted Lipid Nanoparticles for Non-Invasive BBB Delivery

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Solution Overview

Problem

Existing methods for delivering nucleic acids to the central nervous system (CNS) are invasive and face significant challenges due to the impermeability of the blood-brain barrier (BBB), leading to patient discomfort and risks of brain tissue injury.

Innovation Solution

Development of engineered lipid nanoparticles (LNPs) conjugated with an antibody against the CD98hc protein, which allows for non-invasive delivery of nucleic acids across the BBB by binding to the CD98hc, enabling intravenous dosing for neurological disorders.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If invasive surgical intervention is used to deliver nucleic acids to the CNS, then delivery effectiveness is improved, but patient discomfort and risk of brain tissue injury increase

Engineering Contradiction:

Improvedelivery effectivenessVSAvoidpatient discomfort and risk of brain tissue injury

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent uses an antibody conjugated to the LNP as an intermediary that binds to CD98hc transporters on the BBB, facilitating nucleic acid delivery without requiring invasive surgery. The antibody acts as a mediator that bridges the gap between the circulating LNP and the brain tissue, enabling passive delivery through the BBB via transporter-mediated endocytosis.

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent replaces the mechanical invasive surgical intervention system with a biochemical delivery system. Instead of physically introducing nucleic acids into the brain through surgery, the system uses molecular recognition (antibody-CD98hc binding) and cellular uptake mechanisms to achieve delivery, substituting mechanical force with biochemical interaction.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

2Reliability

If viral delivery systems are used to transport nucleic acids across the BBB, then delivery capability is improved, but toxicity and adverse immune responses increase

Engineering Contradiction:

Improvedelivery capabilityVSAvoidtoxicity and adverse immune responses

Core Design Contradiction:

ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent extracts the harmful viral envelope and genetic material from the delivery system, retaining only the essential function of crossing the BBB. The LNP delivers nucleic acids without the viral capsid and envelope proteins that cause toxicity and immune responses, separating the beneficial delivery function from the harmful viral components.

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The patent usesLNPs as temporary, non-integrating delivery vehicles that perform their function and are then cleared from the body. Unlike viral vectors that can integrate into host genomes and cause long-term issues, LNPs are extracellular, non-infectious, and disappear after delivery, eliminating the risk of viral persistence and chronic immune activation.

Inventive Principle:

Principle #27Cheap short-living objects (Disposable)

3Ease of operation

If non-invasive intravenous dosing is used, then ease of administration is improved, but ability to traverse the BBB is worsened

Engineering Contradiction:

Improveease of administrationVSAvoidability to traverse the BBB

Core Design Contradiction:

Ease of operationVSReliability

Solution Approach 1:

The patent performs preliminary action by pre-conjugating the antibody to the LNP before administration. This pre-formed conjugate is designed to recognize and bind to CD98hc transporters on the BBB, preparing the delivery system in advance to overcome the barrier. The antibody-LNP conjugate is already optimized for BBB interaction, so no additional action is needed at the barrier interface during administration.

Inventive Principle:

Principle #10Preliminary action

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 CD98hc-targeted LNPs provide a versatile therapeutic platform for treating neurological disorders with robust pharmacokinetics, avoiding invasive surgical administration and allowing for tailored nucleic acid delivery.

Implementation Method 1

a non-ligand binder capable of transporting the liposome, lipoplex or LNP across the blood-brain barrier, wherein the non-ligand binder binds to CD98 heavy chain (CD98hc)

Methodology Applied

Scientific EffectAntibody binding:

Data Source

PatentUS20250302987A1Targeted Lipid Nanoparticles

Publication Date: 2025.10.02 ZITRA MEDICINES PTY LTD

AI summary

The present invention relates to engineered targeted lipid nanoparticles (LNPs) comprising a nucleic acid, and compositions thereof, wherein the LNPs or compositions are capable of traversing the blood brain barrier (BBB) and delivering nucleic acid cargoes to a target tissue or cell in the central nervous system. In one aspect, the invention relates to the treatment of a neurological disease or disorder with a LNP or composition of the invention.