Multiplexed In Vivo Screening for Functional Cargo Delivery
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Solution Overview
Problem
Current methods for characterizing delivery vehicles, such as nanoparticles, are inefficient in predicting in vivo delivery and functional cargo delivery to specific cells or tissues, due to factors like pulsatile blood flow and heterogeneous vasculature.
Innovation Solution
The use of compositions and methods that include a reporter and a chemical composition identifier in delivery vehicles, allowing for the identification of formulations that deliver cargo functionally to cells by pooling and administering multiple vehicle formulations to a non-human mammal and sorting cells based on detectable signals.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If multiple delivery vehicle formulations are screened in vitro, then screening efficiency is improved, but prediction of in vivo delivery is worsened
Solution Approach 1:
The patent introduces an in vivo screening model using immunocompromised mice as an intermediary system between in vitro assays and human clinical outcomes. The mice receive human blood, liver, and other tissues, creating a humanized physiological environment that better predicts in vivo delivery while maintaining screening efficiency. This intermediary model bridges the gap between simplified in vitro conditions and complex human in vivo physiology.
2Loss of information
If biodistribution is measured, then delivery location information is improved, but functional cargo delivery prediction is worsened
Solution Approach 1:
The patent employs preliminary action by pre-modifying cargo molecules with detectable tags (fluorescent labels, biotin, etc.) before delivery vehicle formulation. These tags are incorporated into the cargo during synthesis, enabling subsequent tracking of functional cargo delivery. This preliminary tagging allows the system to distinguish between mere cargo arrival at target tissues and actual functional delivery into cytoplasm or nucleus, providing precise measurement of functional delivery rather than just biodistribution.
3Reliability
If delivery vehicles are characterized for cargo delivery, then delivery effectiveness is improved, but analysis time and complexity are worsened
Solution Approach 1:
The patent utilizes color changes and optical signal transformations as a rapid readout method for delivery effectiveness assessment. Detectable tags attached to cargo molecules emit fluorescent signals, luminescent signals, or color changes upon reaching target cells or upon cargo release. This optical detection method provides immediate visual or instrumental readout of delivery effectiveness, replacing time-consuming biochemical assays and enabling rapid screening of multiple delivery vehicle formulations.
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 characterization of delivery vehicles that effectively deliver functional cargo to specific cells or tissues, overcoming previous limitations in predicting in vivo delivery and ensuring the cargo is functional.
Implementation Method 1
The reporter can be a nucleic acid such as mRNA that encodes a protein that when expressed in a cell is able to generate a detectable signal. For example, the protein can be a fluorescent protein or an enzyme the produces a detectable substance in the cell.
Implementation Method 2
The cells are sorted using fluorescence activated cell sorting (FACS).
Data Source
AI summary
Disclosed herein are compositions and methods for identifying materials suitable for functional delivery of a bioactive agent to a target tissue. These compositions and methods have the advantage of simultaneously screening a library of materials for the ability to deliver a bioactive agent to a cell, tissue, or organ. The compositions and methods can also be used to confirm that the agent is delivered in a manner sufficient for function of the agent.