Targeted gene modifications in drug discovery and development.
Jean-Pierre Cabaniols1, Luc Mathis, Christophe Delenda
1Cellectis BioResearch, 93230 Romainville, France.
Current Opinion in Pharmacology
|June 16, 2009
Summary
Developing advanced cell-based assays using targeted gene integration in stem cells and primary cells can improve physiological relevance. This approach aims to reduce late-stage clinical trial failures by enhancing screening tools.
Area of Science:
- Biotechnology
- Cell Biology
- Drug Discovery
Background:
- Cell-based assays are crucial for drug discovery and development.
- Current assays often lack physiological relevance, leading to high attrition rates in clinical trials.
Purpose of the Study:
- To review technologies and principles for selecting optimal cell-based assays.
- To highlight trends in cell line development for improved physiological mimicry.
- To propose strategies for reducing late-stage clinical trial failures.
Main Methods:
- Discussion of various cell systems, including stem cells, induced pluripotent stem cells (iPS), and primary cells.
- Evaluation of different gene expression technologies.
- Proposal of targeted gene integration as a preferred method.
Main Results:
- A major trend is expediting cell line development in cellular systems that reflect in vivo physiology.
- Targeted gene integration is presented as a universally applicable and superior expression technology.
- Enhanced screening tools can be developed by combining targeted gene expression with physiologically relevant assays.
Conclusions:
- Targeted gene integration offers a robust approach for cell line development across various cell types.
- Developing assays that better mimic human physiology is key to improving preclinical models.
- These advancements hold the potential to significantly reduce failure and attrition rates in late-stage clinical development.
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