Conditional Replication Viral Vector for Tumor Suppression

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Current cancer therapies using viral vectors for gene therapy face challenges in achieving high incorporation efficiency due to their nonproliferating nature, limiting their effectiveness in targeting and suppressing malignant tumor cells.

Innovation Solution

Development of a viral vector that specifically proliferates and expresses in malignant tumor cells, utilizing a recombinant adenoviral vector with a telomerase promoter and a fusion transcription factor to induce expression of a malignant tumor suppressor protein, SVS-1, which inhibits tumor cell proliferation and metastasis.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If a nonproliferating viral vector is used for gene therapy, then safety is improved, but incorporation efficiency deteriorates

Engineering Contradiction:
ImprovesafetyVSAvoidincorporation efficiency
Core Design Contradiction:
ReliabilityVSProductivity

Solution Approach 1:

The patent changes the proliferation parameter of the viral vector by introducing a conditional replication mechanism. The vector contains an E1A gene that enables replication only in cells expressing specific transcription factors (such as SV40 large T antigen or adenovirus E1A protein), transforming it from a nonproliferating to a conditionally proliferating system. This resolves the contradiction by maintaining safety in normal cells while achieving high incorporation efficiency in target tumor cells through controlled replication.

Inventive Principle:
Principle #35Parameter changes

2Object-generated harmful factors

If a viral vector is designed to proliferate in malignant tumor cells, then antitumor activity is improved, but specificity deteriorates

Engineering Contradiction:
Improveantitumor activityVSAvoidspecificity
Core Design Contradiction:
Object-generated harmful factorsVSAdaptability or versatility

Solution Approach 1:

The patent applies local quality by creating spatially differentiated behavior of the viral vector. The vector is designed to proliferate and exert antitumor activity only in specific locations (tumor cells expressing particular transcription factors) while remaining inert in other locations (normal cells). This is achieved through the conditional replication mechanism that responds to cell-type-specific transcription factors, thereby maintaining high specificity while achieving strong antitumor activity.

Inventive Principle:
Principle #3Local quality

3Object-generated harmful factors

If gene expression is enhanced in the viral vector, then treatment effect is improved, but gene introduction efficiency deteriorates

Engineering Contradiction:
Improvetreatment effectVSAvoidgene introduction efficiency
Core Design Contradiction:
Object-generated harmful factorsVSEase of manufacture

Solution Approach 1:

The patent applies preliminary action by first introducing the viral vector into the target cells, which then replicate and amplify the gene expression internally. The initial gene introduction requires minimal efficiency, but the subsequent viral replication within the cells serves as a self-amplifying mechanism that enhances gene expression levels. This two-stage process (initial introduction followed by internal amplification through replication) resolves the contradiction between treatment effect and introduction efficiency.

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

The viral vector effectively suppresses malignant tumor cells by enhancing gene expression and antitumor activity, specifically targeting cancer cells while minimizing impact on normal cells, thus offering a promising approach for cancer treatment and prevention of recurrence and metastasis.

Implementation Method 1

utilizing a recombinant adenoviral vector with a telomerase promoter and a fusion transcription factor to induce expression of a malignant tumor suppressor protein

Methodology Applied
Scientific EffectPromoter-driven transcription:

Implementation Method 2

a viral vector proliferating and being expressed specifically in malignant tumor cells

Methodology Applied
Scientific EffectViral replication:

Implementation Method 3

the gene has a function to inhibit proliferation of malignant tumor cells

Methodology Applied
Scientific EffectTumor suppression:

Data Source

PatentUS8956606B2Malignant tumor cell suppressor protein, malignant tumor cell suppressor gene, maligant tumor cell suppressive viral vector, and kit using the same
Publication Date: 2015.02.17 ANDOH TOSHIWO
  • US8956606B2 patent drawing
  • US8956606B2 patent drawing
  • US8956606B2 patent drawing

AI summary

A malignant tumor cell suppressor protein (a) or (b):(a) a protein comprising an amino acid sequence represented by SEQ ID No. 1; or(b) a protein comprising an amino acid sequence represented by SEQ ID No. 1, wherein one or more amino acid are deleted, substituted or added in the amino acid sequence set forth in SEQ ID No. 1.