Virus Microbubble Delivery Selectivity via Inactivation

Solution Overview

Problem

Current methods for delivering viruses using ultrasound-guided microbubbles result in non-selective delivery due to the presence of free viruses associated with the contrast agent preparation, leading to unintended sites receiving the genetic material, such as extensive β-galactosidase activity in the livers of animals despite targeted delivery to the heart.

Innovation Solution

Encapsulating the virus within a microbubble and treating the preparation with a virus-inactivating agent to inactivate unencapsulated viruses, followed by administering the microbubble composition and directing ultrasound waves to the specific site for controlled release of the virus.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If viruses are delivered using ultrasound-guided microbubbles, then the delivery process can be visualized and controlled, but non-selective delivery occurs due to free viruses associated with the contrast agent preparation

Engineering Contradiction:

Improvedelivery selectivityVSAvoidfree virus contamination

Core Design Contradiction:

Measurement precisionVSObject-generated harmful factors

Solution Approach 1:

The patent extracts and removes free viruses from the microbubble preparation through filtration or centrifugation processes before administration. This separation ensures that only viruses encapsulated within microbubbles are delivered to the target site, eliminating non-selective delivery caused by free viral particles circulating in the bloodstream.

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The patent applies preliminary treatment steps including filtration and centrifugation to the microbubble preparation before it is administered to the patient. These preliminary actions remove free viruses from the preparation, ensuring that the subsequent ultrasound-guided delivery process only delivers encapsulated viruses to the intended target site.

Inventive Principle:

Principle #10Preliminary action

2Device complexity

If free viruses are present in the microbubble preparation, then the preparation can be simplified, but unintended sites receive genetic material leading to non-specific transduction

Engineering Contradiction:

Improvepreparation complexityVSAvoidnon-specific transduction

Core Design Contradiction:

Device complexityVSObject-affected harmful factors

Solution Approach 1:

The patent extracts and removes free viruses from the microbubble preparation through filtration or centrifugation processes before administration. This separation ensures that only viruses encapsulated within microbubbles are delivered to the target site, eliminating non-selective delivery caused by free viral particles circulating in the bloodstream.

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The patent applies preliminary treatment steps including filtration and centrifugation to the microbubble preparation before it is administered to the patient. These preliminary actions remove free viruses from the preparation, ensuring that the subsequent ultrasound-guided delivery process only delivers encapsulated viruses to the intended target site.

Inventive Principle:

Principle #10Preliminary action

3Ease of operation

If viruses are not encapsulated within microbubbles, then the delivery process is simpler, but the viruses cannot be selectively released at the targeted site

Engineering Contradiction:

Improvedelivery process simplicityVSAvoidsite-selective delivery precision

Core Design Contradiction:

Ease of operationVSManufacturing precision

Solution Approach 1:

The patent employs nested structures where viruses are encapsulated within microbubble shells. This nesting arrangement allows the viruses to be protected during circulation and then selectively released at the target site through ultrasound-induced microbubble destruction, achieving both simplicity in administration and precision in delivery.

Inventive Principle:

Principle #7Nested doll (Nesting)

Solution Approach 2:

The patent applies preliminary treatment steps including filtration and centrifugation to the microbubble preparation before it is administered to the patient. These preliminary actions remove free viruses from the preparation, ensuring that the subsequent ultrasound-guided delivery process only delivers encapsulated viruses to the intended target site.

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

This approach enables site-selective delivery of viruses by ensuring that only encapsulated viruses are released at the targeted site, reducing non-specific transduction and enhancing the precision of genetic material delivery.

Implementation Method 1

a virus encapsulated within a microbubble

Methodology Applied

Scientific EffectPhysical containment: Physical Containment

Implementation Method 2

directing ultrasound waves to the specific site for controlled release of the virus

Methodology Applied

Scientific EffectUltrasound: Ultrasound

Implementation Method 3

treating the preparation with a virus-inactivating agent to inactivate unencapsulated viruses

Methodology Applied

Scientific EffectVirus inactivation:

Data Source

PatentUS8454937B2Method and composition for the site-selective delivery using viruses encapsulated in microbubbles

Publication Date: 2013.06.04 TEMPLE UNIV

AI summary

Methods and compositions for the site-selective delivery of a gene to a site within the body of an animal where virus not encapsulated within the microbubbles is inactivated, for example by treatment with a virus-inactivating agent.