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Updated: Jul 8, 2026
08:54
In vivo Application of the REMOTE-control System for the Manipulation of Endogenous Gene Expression
Published on: March 29, 2019
A humanized system for pharmacologic control of gene expression
V M Rivera1, T Clackson, S Natesan
1ARIAD Gene Therapeutics, Cambridge, Massachusetts 02139, USA.
Nature Medicine
|September 1, 1996
Summary
Researchers developed a novel gene therapy system for precise control of therapeutic protein production. This system uses an orally administered drug to regulate protein levels, offering a safer and more effective treatment approach.
Area of Science:
- Biotechnology
- Gene Therapy
- Pharmacology
Background:
- Gene therapy traditionally targets inherited disorders by correcting defective genes.
- Emerging applications include using gene therapy as a delivery platform for protein therapeutics like hormones and antibodies.
- Precise control over therapeutic protein production is a critical challenge for widespread gene therapy implementation.
Purpose of the Study:
- To design a gene expression system for pharmacologic control of therapeutic protein production.
- To achieve precise dosage titration, intermittent treatment, and on-demand termination of gene therapy.
- To create a modular system using exclusively human proteins to minimize immune responses.
Main Methods:
- Development of a novel gene expression system with low baseline expression and high induction ratio.
- Utilized an orally bioavailable small-molecule drug for positive control.
- Employed protein engineering tools for modular optimization of system components.
- Demonstrated control of human growth hormone levels in engineered cells in mice.
Main Results:
- Successfully designed and characterized a controllable gene expression system.
- Achieved precise regulation of therapeutic protein levels in vivo.
- The system exhibited low baseline expression and a high induction ratio.
- Demonstrated the potential for intermittent or pulsatile protein delivery.
Conclusions:
- The developed gene therapy system offers precise pharmacologic control over therapeutic protein production.
- This system has broad potential for delivering protein therapeutics with enhanced safety and efficacy.
- The modular design allows for future optimization and adaptation for various therapeutic proteins.
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