Therapeutic protein aggregation: mechanisms, design, and control.

Area of Science:

• Biochemistry
• Protein Science
• Drug Development

Background:

• Proteins are marginally stable in folded states.
• Unfolded or partially unfolded proteins are prone to aggregation.
• Protein aggregates can be stable and long-lived, posing risks.

Purpose of the Study:

• To highlight the inherent aggregation-prone nature of proteins.
• To emphasize the significance of protein aggregates in therapeutic applications.
• To propose a mechanistic approach for controlling protein aggregation.

Main Methods:

• Analysis of protein aggregation mechanisms.
• Review of factors influencing protein aggregation.
• Exploration of strategies for therapeutic protein design.

Main Results:

• Most proteins inherently aggregate in unfolded states.
• Therapeutic protein aggregates can trigger immune responses.
• Balancing protein environment and inherent aggregation propensities is crucial.

Conclusions:

• Understanding and controlling protein aggregation is vital for therapeutic protein development.
• Mechanistic control of aggregation complements existing design strategies.
• Protein environment plays a key role in mitigating aggregation.