Aptamer-Based Diagnostics for Microvesicle Surface Antigens

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Solution Overview

Problem

Current diagnostic and therapeutic approaches for cancer and other diseases involving microvesicles lack specificity and efficiency, particularly in targeting microvesicle surface antigens, which are shed from cancer cells, due to limitations in antibody-based therapies such as immunogenicity, scalability, and delivery methods.

Innovation Solution

Development of aptamers that are nucleic acid molecules with specific binding affinity to microvesicle surface antigens, allowing for targeted diagnostics and therapeutics through subcutaneous administration, high specificity, and efficient delivery, including chemical modifications and conjugations for enhanced functionality.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If antibody-based therapies are used to target microvesicle surface antigens, then binding affinity can be achieved, but immunogenicity and scalability are limited

Engineering Contradiction:

Improvebinding affinityVSAvoidimmunogenicity

Core Design Contradiction:

ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent uses aptamers as molecular copies or mimics of antibodies that bind to the same microvesicle surface antigens (such as CD9, CD63, CD81, EpCAM, PSMA) but without the immunogenicity problems of traditional antibodies. The aptamers are nucleic acid molecules that replicate the binding function of antibodies while avoiding their harmful immunogenic effects.

Inventive Principle:

Principle #26Copying

Solution Approach 2:

The patent replaces the protein-based antibody system with a nucleic acid-based aptamer system. This substitution eliminates the immunogenicity issue inherent in protein therapeutics while maintaining binding affinity through nucleic acid-target interactions, thereby resolving the contradiction between binding capability and immunogenicity.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

2Reliability

If antibody-based therapies are used to target microvesicle surface antigens, then binding affinity can be achieved, but scalability and delivery methods are limited

Engineering Contradiction:

Improvebinding affinityVSAvoidscalability

Core Design Contradiction:

ReliabilityVSEase of manufacture

Solution Approach 1:

The patent changes the fundamental parameter of the therapeutic molecule from protein (antibody) to nucleic acid (aptamer). This parameter change enables superior scalability through chemical synthesis rather than biological production, allows for easier modification of binding specificity by changing nucleotide sequences, and improves delivery characteristics through subcutaneous administration with high bioavailability.

Inventive Principle:

Principle #35Parameter changes

3Productivity

If traditional diagnostic approaches are used for cancer detection, then general screening can be performed, but specificity for microvesicle surface antigens is insufficient

Engineering Contradiction:

Improvediagnostic screening capabilityVSAvoidspecificity

Core Design Contradiction:

ProductivityVSMeasurement precision

Solution Approach 1:

The patent applies local quality by designing aptamers with specific nucleic acid sequences that are complementary to particular microvesicle surface antigens (such as CD9, CD63, CD81, EpCAM, PSMA). Each aptamer is optimized to bind with high specificity to its target antigen, enabling precise detection of cancer-specific microvesicles while maintaining efficient diagnostic screening capability.

Inventive Principle:

Principle #3Local quality

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

Aptamers provide a highly specific and effective means for diagnosing and treating diseases by binding to microvesicle surface antigens, offering improved delivery and reduced immunogenicity, enabling precise modulation of biological activity and enhanced therapeutic outcomes.

Implementation Method 1

Aptamers are nucleic acid molecules having specific binding affinity to molecules through interactions other than classic Watson-Crick base pairing

Methodology Applied

Scientific EffectMolecular recognition:

Implementation Method 2

Aptamers are capable of using the same types of binding interactions (e.g., hydrogen bonding, electrostatic complementarity, hydrophobic contacts, steric exclusion) that drive affinity and specificity in antibody-antigen complexes

Methodology Applied

Scientific EffectHydrogen bonding:

Implementation Method 3

Methodology Applied

Scientific EffectElectrostatic complementarity: Electrostatics

Implementation Method 4

Methodology Applied

Scientific EffectHydrophobic contacts: Hydrophobe

Data Source

PatentEP4170031A1Aptamers and uses thereof

Publication Date: 2023.04.26 CARIS SCIENCE INC

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AI summary

Methods and compositions are provided for specific aptamers and aptamer pools that bind biomarkers of interest such as microvesicle surface antigens or functional fragments of microvesicle surface antigens. In various embodiments, aptamers of the invention are used in diagnostic, prognostic, or theranostic processes to screen a biological sample for the presence or levels of biomarkers such as micro vesicles that are determined to provide a diagnostic, prognostic, or theranostic readout. The diagnosis, prognosis, or theranosis may be related to cancer or other diseases and disorders. The invention also provides methods and composition to facilitate aptamer library screening and aptamer detection methods.