Exploiting protein domain modularity to enable synthetic control of engineered cells

Area of Science:

• Biochemistry
• Synthetic Biology
• Cellular Engineering

Background:

• Precise control of cellular function is crucial for improving cell therapy efficacy and safety.
• Protein domain modularity, the ability to combine or separate functional protein units, is a key biological principle.
• Natural protein evolution involves domain fusion and fission, providing a basis for synthetic applications.

Purpose of the Study:

• To review how protein domain modularity is utilized for cellular control applications.
• To highlight advances in synthetic constructs and split moieties for enhanced cellular function.
• To showcase the therapeutic potential of engineered proteins in cell therapies.

Main Methods:

• Exploiting the modularity of protein domains for designing synthetic constructs.
• Developing controllable split protein moieties.
• Harnessing natural protein evolutionary tendencies for cellular engineering.
• Engineering novel immunoreceptors, base editors, and cytokines.

Main Results:

• Demonstrated the creation of multifunctional synthetic constructs for cellular control.
• Showcased the development of controllable split moieties for precise cellular regulation.
• Highlighted engineered proteins with significant therapeutic potential.
• Enabled cells to acquire new functions through synthetic biology approaches.

Conclusions:

• Protein modularity is a powerful enabling phenomenon for cellular engineering.
• Synthetic biology approaches leveraging protein modularity enhance control over cellular phenotypes.
• These advances offer promising avenues for developing next-generation cell therapies.