Extracellular Vesicles Targeting LAT1 for Brain Delivery
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Solution Overview
Problem
Delivering therapeutic agents, such as antisense oligonucleotides, across the blood-brain barrier and into specific brain regions is challenging due to the barrier's restrictive nature and the cell membrane's exclusion of highly charged molecules, limiting the effectiveness of treatments for brain disorders.
Innovation Solution
Extracellular vesicles (EVs) are engineered with a targeting moiety capable of being transported by the large neutral amino acid transporter 1 (LAT1), allowing them to carry biologically active molecules, including antisense oligonucleotides, across the blood-brain barrier and into target cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If therapeutic agents are delivered across the blood-brain barrier, then treatment effectiveness for brain disorders is improved, but the restrictive nature of the BBB excludes most therapeutic molecules
Solution Approach 1:
The patent uses extracellular vesicles as intermediary carriers to transport therapeutic agents across the blood-brain barrier. The EVs serve as a mediator that facilitates the passage of molecules that would otherwise be excluded by the barrier, enabling delivery of antisense oligonucleotides and other therapeutics to brain tissue.
2Adaptability or versatility
If highly charged therapeutic agents such as oligonucleotides are used, then therapeutic payload is improved, but the cell membrane effectively excludes these charged molecules
Solution Approach 1:
The patent employs extracellular vesicles as intermediary carriers to transport highly charged therapeutic agents like antisense oligonucleotides across the cell membrane. The EV membrane facilitates the passage of these charged molecules that would otherwise be excluded by the selectively permeable cell membrane.
Solution Approach 2:
The patent loads therapeutic agents such as antisense oligonucleotides inside the extracellular vesicles. The EV structure acts as a nested container that protects and transports the therapeutic payload through biological barriers, delivering it to the target cytosol or nucleus.
3Reliability
If therapeutic molecules are formulated for delivery, then pharmacological properties are improved, but delivery to the right organ, tissue, or cell remains challenging
Solution Approach 1:
The patent modifies the surface properties of extracellular vesicles to enable specific targeting of brain tissue and cells. By conferring brain-specific or cell-specific properties to the EV surface, the system achieves localized delivery to the intended target while maintaining systemic circulation, thereby improving both pharmacological properties and delivery precision.
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 approach enables the targeted delivery of therapeutic agents to the brain, overcoming the limitations of existing delivery methods and improving the pharmacological properties of therapeutic payloads, such as serum stability and tissue specificity.
Implementation Method 1
the targeting moiety is capable of being transported by large neutral amino acid transporter 1 (LAT1)
Data Source
AI summary
The present disclosure relates to extracellular vesicles (e.g., exosomes) comprising a targeting moiety and a biologically active molecule via an optional linker, which may be useful as an agent for the prophylaxis or treatment of diseases. Also provided herein are methods for producing the extracellular vesicles and methods for using the extracellular vesicles to treat diseases or disorders.