Immortalized Rousettus Cell Line for Viral Amplification

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Solution Overview

Problem

Current technologies lack effective cell lines derived from bats, particularly Megachiroptera, for the amplification and production of microbial agents, which are crucial for diagnostic and therapeutic purposes, due to the limited availability of bat cell lines and the challenges in generating immortalized cell lines from megabats.

Innovation Solution

An immortalized cell line from the Megachiropteran Rousettus aegyptiacus is developed through liposomal transfection of E1 genes from human adenovirus serotype 5, enabling efficient permissivity and replication of the highly attenuated modified vaccinia Ankara (MVA) virus, and deposited under DSM ACC2902, facilitating the production and diagnosis of microbial agents.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If conventional cell lines are used for microbial agent production, then production capacity is limited, but the patent develops immortalized bat cell lines to overcome this limitation

Engineering Contradiction:
Improvemicrobial agent production capacityVSAvoidcell line development complexity
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The patent applies preliminary action by pre-immortalizing bat cells through transfection with adenovirus E1 genes before use in microbial agent production. This creates a permanent, highly productive cell line (Rousettus aegyptiacus epithelial cells) that can be repeatedly used for virus amplification, eliminating the need to start from primary cells each time and significantly increasing overall productivity.

Inventive Principle:
Principle #10Preliminary action

2Reliability

If immortalized cell lines are generated from megabats, then availability of host cells for pathogen amplification improves, but the technical challenge of generating such cell lines increases

Engineering Contradiction:
Improveavailability of bat cell linesVSAvoiddifficulty in generating immortalized cell lines
Core Design Contradiction:
ReliabilityVSEase of manufacture

Solution Approach 1:

The patent uses adenovirus E1 genes as an intermediary to achieve immortalization of bat cells. The E1 genes, when transfected into primary bat cells, provide the necessary functions for continuous cell division and prevention of senescence. This intermediary approach simplifies the generation of immortalized cell lines compared to direct manipulation of multiple cell cycle pathways simultaneously.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent changes the biological parameters of bat cells by introducing foreign genetic material (adenovirus E1 genes) that fundamentally alters cell behavior from finite lifespan to immortal proliferation. This parameter change in cellular immortality transforms the cells into reliable, reusable hosts for pathogen amplification.

Inventive Principle:
Principle #35Parameter changes

3Quantity of substance

If high titers of viral agents are produced, then diagnostic and therapeutic effectiveness improves, but the complexity of achieving efficient replication increases

Engineering Contradiction:
Improveviral titerVSAvoidreplication system complexity
Core Design Contradiction:
Quantity of substanceVSDevice complexity

Solution Approach 1:

The patent creates a universal host cell system (immortalized Rousettus aegyptiacus cells) that can support replication of multiple different viral agents including vaccinia, adenovirus, and other pathogens. This multi-functional cell line eliminates the need to develop separate cell systems for each virus, achieving high titers across different viral targets through a single, versatile platform.

Inventive Principle:
Principle #6Universality (Multi-functionality)

Data Source

PatentUS8679839B2Cell line from rousettus as host cell for pathogen amplification
Publication Date: 2014.03.25 PROBIOGEN AG
  • US8679839B2 patent drawing
  • US8679839B2 patent drawing
  • US8679839B2 patent drawing

AI summary

The present invention relates to permanent cell lines from chiropterans suitable for amplification and production of microbial agents, preferably viruses, and its use for diagnostic or therapeutic purposes.