Engineered Receptor-Ligand System for Targeted Drug Delivery
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing targeted delivery systems for therapeutic and diagnostic agents face challenges in specificity, particularly when delivering agents across barriers like the blood-brain barrier, due to the expression of endogenous receptors in non-target tissues, leading to non-specific delivery.
Innovation Solution
Development of an engineered receptor-ligand system where a non-naturally occurring receptor is expressed in the target tissue, allowing for specific binding and transport of therapeutic or diagnostic agents across barriers, using a ligand that binds selectively to the engineered receptor.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If endogenous receptors are used for targeted delivery, then delivery to blood-brain barrier is achieved, but specificity is reduced due to expression in other tissues
Solution Approach 1:
The patent applies local quality by creating a receptor that is artificially introduced and expressed only in the specific target tissue (blood-brain barrier or blood-cerebrospinal fluid barrier) rather than being naturally expressed throughout the body. This localized expression enables specific delivery to the intended target while avoiding non-specific binding in other tissues.
Solution Approach 2:
The patent uses an engineered receptor as an intermediary molecule that mediates the delivery process. This receptor is not naturally present in the subject but is introduced to facilitate specific binding and transport of the therapeutic or diagnostic agent across the barrier, serving as a temporary mediator that achieves the desired delivery effect.
2Manufacturing precision
If engineered receptor is introduced into subject, then delivery specificity is improved, but device complexity increases
Solution Approach 1:
The patent extracts the receptor function from its natural context and creates a simplified engineered version that performs only the necessary function (binding and transporting the agent across the barrier). By taking out the receptor from its natural physiological role and creating a minimal functional version, the system achieves specificity without requiring the full complexity of natural receptor systems.
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 targeted and specific delivery of therapeutic or diagnostic agents to the intended tissue, reducing off-target effects and lowering required dosages, while enhancing the effectiveness of the delivery process.
Implementation Method 1
a ligand for the engineered receptor can then be associated with a therapeutic or diagnostic agent of interest and administered to the subject, resulting in specific, targeted delivery of the agent to the tissue expressing the engineered receptor
Data Source
AI summary
Provided herein are compositions and methods related to targeted delivery of a therapeutic or diagnostic agent to a subject utilizing an engineered receptor-ligand system, such as an engineered dockerin-cohesin system. As described herein, previously-developed targeted delivery systems for delivering therapeutic and diagnostic agents to a tissue of interest have drawbacks that have not been addressed to date. For example, with respect to the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB), both of which hamper delivery of agents to the brain, others have relied on the use of endogenously expressed receptors, like the transferrin receptor, to assist the agent across the barriers.