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Mimicking the Function of Signaling Proteins: Toward Artificial Signal Transduction Therapy

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Function-based mutation-resistant synthetic signaling device activated by HIV-1 proteolysis.

Andreja Majerle¹, Rok Gaber¹, Mojca Benčina¹

¹†Laboratory of Biotechnology, National Institute of Chemistry, Hajdrihova 19, 1000 Ljubljana, Slovenia.

ACS Synthetic Biology

|November 14, 2014

Summary

This study presents a novel synthetic biology approach for detecting human immunodeficiency virus type 1 (HIV-1) by sensing viral function, not just proteins. This method effectively detects drug-resistant HIV-1 mutants.

Keywords:

HIV-1 protease drug-resistant mutants genetic device protease-activated transcription factor synthetic biology

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Area of Science:

Synthetic Biology
Virology
Molecular Biology

Background:

Human immunodeficiency virus type 1 (HIV-1) exhibits a high mutation rate, enabling evasion of antibodies and inhibitors.
Current detection methods often target specific viral proteins, which can be circumvented by mutations.

Purpose of the Study:

To develop a viral detection strategy based on synthetic biology principles.
To create a sensor that detects a specific viral function rather than a particular viral protein, overcoming resistance issues.

Main Methods:

Engineered a genetically encoded sensor in a human cell line, comprising a membrane anchor, HIV-1 protease target site, and a transcriptional activator.
The sensor releases the transcriptional activator upon cleavage by the HIV-1 protease, initiating gene transcription.

Main Results:

The engineered sensor successfully detected HIV-1 protease activity.
The system remained highly activated even with clinically relevant protease mutants resistant to existing inhibitors.

Conclusions:

This synthetic biology-based sensor offers a robust method for detecting HIV-1, circumventing challenges posed by viral mutations.
The principle can be extended for the detection of other pathogens and their essential functions.