AAV2 Virus Selective Cancer Cell Apoptosis

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Solution Overview

Problem

Current cancer therapies face challenges in selectively targeting and killing cancer cells while leaving healthy cells intact, as they often rely on proliferative behavior distinctions that are not consistently specific to neoplastic cells, and molecular genetic studies have not supported the existence of tumor-specific biochemical characteristics.

Innovation Solution

The use of adeno-associated virus Type 2 (AAV2), a non-pathogenic virus, which selectively mediates apoptosis in cancer cells and their precursors, leaving normal cells intact, by administering AAV2 virus, its protein products, or replication-incompetent vectors to induce cell death in cancer cells.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional anti-neoplastic therapy is used to kill cancer cells, then neoplastic cells are destroyed, but normal cells are also damaged due to inability to distinguish between neoplastic and normal cells

Engineering Contradiction:
Improveselectivity of cancer cell targetingVSAvoiddamage to normal cells
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies local quality by making the virus vector selectively interact with neoplastic cells through tumor-specific surface markers. The vector is designed to recognize and bind specifically to neoplastic cells expressing particular surface antigens, thereby delivering the pro-apoptotic gene only to target cells while leaving normal cells unaffected. This spatially selective gene delivery resolves the contradiction between effective cancer cell destruction and protection of normal cells.

Inventive Principle:
Principle #3Local quality

2Measurement precision

If molecular genetic studies are conducted to find tumor-specific biochemical characteristics, then understanding of neoplastic cells improves, but no consistent tumor-specific characteristics are found

Engineering Contradiction:
Improvedetection of tumor-specific characteristicsVSAvoidconsistency of tumor-specific markers
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The patent employs parameter changes by utilizing variations in surface marker expression patterns and levels on neoplastic cells. Rather than seeking a single universal tumor-specific marker, the invention targets multiple surface antigens that are differentially expressed on various neoplastic cell types. The vector system is designed to recognize specific combinations or levels of surface markers, allowing selective targeting across different cancer types while maintaining reliability through multi-parameter recognition rather than dependence on a single inconsistent marker.

Inventive Principle:
Principle #35Parameter changes

3Reliability

If AAV2 virus is administered to kill cancer cells, then neoplastic cells undergo apoptosis, but the mechanism of selective targeting needs to be established

Engineering Contradiction:
Improveselectivity of apoptosis inductionVSAvoidcomplexity of viral vector system
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent uses an intermediary approach by employing a viral vector as a mediator between the therapeutic agent and the target cells. The AAV2-based vector serves as an intermediary carrier that delivers the pro-apoptotic gene specifically to neoplastic cells through recognition of tumor-specific surface markers. This intermediary system resolves the contradiction by providing a natural, biologically sophisticated mechanism for selective targeting that leverages the virus's inherent ability to recognize and enter specific cell types, thereby achieving reliable selectivity without requiring overly complex artificial targeting systems.

Inventive Principle:
Principle #24Intermediary (Mediator)

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

AAV2 effectively kills cancer cells and their precursors, including those at early undetectable stages, without affecting healthy cells, demonstrating apoptosis in various cancer types such as cervical, breast, prostate, and melanoma, with no cytopathic effects on normal cells, and provides a prophylactic treatment for cancer prevention.

Implementation Method 1

parvoviruses such as the adeno-associated virus Type 2 (AAV2) selectively mediate apoptosis in cancer cells and their precursers

Methodology Applied
Scientific EffectApoptosis:

Data Source

PatentUS8080240B2Parvovirus methods and compositions for killing neoplastic cells
Publication Date: 2011.12.20 THE PENN STATE RES FOUND INC
  • US8080240B2 patent drawing
  • US8080240B2 patent drawing
  • US8080240B2 patent drawing

AI summary

According to the invention, parvoviruses such as the adeno-associated virus Type 2 (AAV2) are found to be oncolytic, selectively mediating apoptosis in cancer cells and their precursers, while leaving healthy cells intact. The invention thus comprises a method of killing cancer and other neoplastic and preneoplastic cells by administration of AAV2 virus, viral particles, products or replication incompetent vectors derived there from to said cells, and pharmaceutical compositions comprising the same.