Peripheral AAV Vector Delivery to CNS via Choroid Plexus

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Solution Overview

Problem

Existing methods for delivering therapeutic proteins to the central nervous system (CNS) require direct injection into the brain, which poses risks such as infection and inflammation due to the blood-brain barrier, limiting their clinical application.

Innovation Solution

Peripheral administration of recombinant AAV vectors that infect cerebrospinal fluid secretory cells like the epithelial cells of the plexus choroids and/or ependyma, allowing secretion of therapeutic proteins into the cerebrospinal fluid.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If direct injection of gene vectors into the brain is performed, then therapeutic proteins can be delivered to the CNS, but risks of infection and inflammation increase due to blood-brain barrier disruption

Engineering Contradiction:

Improvetherapeutic protein delivery to CNSVSAvoidinfection and inflammation risk

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent uses the choroid plexus epithelial cells as an intermediary structure. Instead of directly injecting vectors into the brain, the vectors are introduced peripherally and transported to the choroid plexus cells, which then secrete therapeutic proteins into the cerebrospinal fluid. This intermediary approach allows CNS delivery while avoiding direct brain invasion and blood-brain barrier disruption.

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent replaces the mechanical direct injection method with a biological transport system. Rather than physically penetrating the blood-brain barrier through stereotaxic injection, the system uses the natural secretory function of choroid plexus cells to deliver therapeutic proteins into the CNS environment, substituting mechanical force with biological processes.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

2Duration of action of moving object

If stereotaxic implantation of catheter and osmotic minipump is used, then continuous production of therapeutic proteins in cerebral ventricles is achieved, but device complexity and surgical intervention increase

Engineering Contradiction:

Improvecontinuous production of therapeutic proteinsVSAvoidcatheter and osmotic minipump system

Core Design Contradiction:

Duration of action of moving objectVSDevice complexity

Solution Approach 1:

The patent employs the body's own choroid plexus cells to perform the function of continuous protein production and secretion. These endogenous cells are transduced by the viral vectors and then autonomously produce and secrete therapeutic proteins into the cerebrospinal fluid, eliminating the need for external pumps or catheters to maintain continuous delivery.

Inventive Principle:

Principle #25Self-service

Solution Approach 2:

The patent extracts the essential function of continuous protein delivery from the complex mechanical system (pump and catheter) and transfers it to the biological system (choroid plexus cells). By isolating and utilizing the natural secretory capability of these cells, the invention removes the need for cumbersome external delivery devices.

Inventive Principle:

Principle #2Taking out (Extraction)

3Reliability

If intra-cerebral surgery is performed for direct vector injection, then gene delivery to CNS is achieved, but surgical risks and patient trauma increase

Engineering Contradiction:

Improvegene delivery to CNSVSAvoidsurgical procedure complexity

Core Design Contradiction:

ReliabilityVSEase of operation

Solution Approach 1:

The patent inverts the traditional delivery approach by working from the periphery inward rather than from the center outward. Instead of injecting vectors directly into the brain through surgery, the vectors are introduced through peripheral routes (systemic circulation) and then transported to the choroid plexus, which serves as a gateway to the CNS. This inversion eliminates the need for invasive brain surgery.

Inventive Principle:

Principle #13The other way round (Inversion)

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

This method achieves safe and efficient delivery of therapeutic proteins to the CNS, bypassing the need for invasive brain injections and overcoming the blood-brain barrier, suitable for treating various CNS disorders.

Implementation Method 1

the transcytosis property (i.e., active membrane transport) of AAV through the epithelium barrier

Methodology Applied

Scientific EffectTranscytosis:

Data Source

PatentUS20250333765A1CNS gene delivery using peripheral administration of AAV vectors

Publication Date: 2025.10.30 GENETHON

AI summary

The present invention relates to compositions and methods for the delivery of therapeutic proteins to the CNS using recombinant AAV vectors. More specifically, the invention relates to compositions and methods for delivering proteins into the cerebrospinal fluid of mammalian subjects through peripheral administration of AAV vectors. The invention may be used to treat various disorders of the central nervous system, including degenerative diseases and motor neuron diseases.