Droplet microfluidic screening to engineer angiotensin-converting enzyme 2 (ACE2) catalytic activity.
Summary
A droplet microfluidic platform screens peptidases on native peptide substrates by detecting free amino acid release, enabling discovery of higher-activity ACE2 variants. The K187T ACE2 variant showed approximately 4-fold higher catalytic efficiency, demonstrating a route to engineer ACE2 for ARDS- and infection-relevant therapeutics.
Key Findings
- Developed a droplet microfluidic assay that quantifies native-substrate cleavage via free amino acid release.
- Identified ACE2 position 187 as an activity hotspot; K187T variant achieved ~4-fold higher catalytic efficiency.
- Demonstrated a scalable, accessible platform for therapeutic peptidase engineering.
Clinical Implications
Engineered ACE2 with enhanced catalytic efficiency could improve therapies aiming to rebalance the renin–angiotensin system in ARDS and viral lung disease; the platform generalizes to other peptidases for drug development.
Why It Matters
Introduces an accessible, ultra-high-throughput method that avoids surrogate-substrate artifacts, with immediate utility for engineering therapeutic enzymes like ACE2.
Limitations
- Preclinical engineering study; no in vivo efficacy or safety data for engineered ACE2 variants.
- Catalytic gains on selected substrates may not generalize across all physiologic targets.
Future Directions
Evaluate engineered ACE2 in relevant ARDS/viral infection models and optimize stability, specificity, and delivery; extend the platform to other therapeutic peptidases.
Study Information
- Study Type
- Case series
- Research Domain
- Treatment
- Evidence Level
- IV - Experimental engineering and screening study without clinical testing.
- Study Design
- OTHER