Post-Transcriptional Modular Synthetic Receptors
Xiaowei Zhang1,2, Luis S Mille-Fragoso1,2,3, K Eerik Kaseniit1,3
1Department of Bioengineering, Stanford University; Stanford, 94305, USA.
Biorxiv : the Preprint Server for Biology
|May 15, 2024
Summary
We developed LIDAR (Ligand-Induced Dimerization Activating RNA editing), a novel synthetic receptor platform for cell engineering. This RNA editing tool senses diverse ligands and enables complex cellular programming for research and therapeutics.
Area of Science:
- Synthetic biology
- Molecular engineering
- Cellular engineering
Background:
- Transcriptional synthetic receptors are powerful tools for cell engineering.
- There is a need for complementary post-transcriptional systems to expand the cell engineering toolbox.
Purpose of the Study:
- To establish a modular post-transcriptional synthetic receptor platform harnessing RNA editing by ADAR.
- To create a versatile system for sensing diverse ligands and producing functional outputs.
- To enable orthogonal signal sensing and synthetic spatial patterning for complex multicellular behaviors.
Main Methods:
- Development of the Ligand-Induced Dimerization Activating RNA editing (LIDAR) platform.
- Utilizing ADAR enzyme for RNA editing-based synthetic receptor function.
- Demonstrating compatibility with various receptor architectures and cellular contexts.
- Encoding LIDAR via synthetic mRNA for delivery.
Main Results:
- LIDAR functions as a modular, post-transcriptional synthetic receptor.
- The platform successfully senses diverse ligands and generates functional outputs.
- LIDAR enables orthogonal signal sensing and synthetic spatial patterning within cells.
- Compact encoding and mRNA delivery are compatible with LIDAR.
Conclusions:
- LIDAR expands the family of synthetic receptors for cell engineering.
- The platform holds promise for advancing basic research and therapeutic applications.
- LIDAR offers a novel approach to programming complex multicellular behaviors.
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