Supramolecular Enzyme-Peptide Gels for Localized Therapeutic Biocatalysis

Area of Science:

• Biomaterials Science
• Enzyme Engineering
• Drug Delivery Systems

Background:

• Enzyme therapeutics face challenges with poor tissue accumulation and off-target effects due to high required doses.
• Developing localized delivery systems is crucial for enhancing enzyme therapeutic efficacy and safety.

Purpose of the Study:

• To develop an injectable supramolecular enzyme-peptide gel platform for prolonged local enzyme retention *in vivo*.
• To demonstrate the versatility and therapeutic potential of this enzyme-peptide gel system.

Main Methods:

• Fabrication of enzyme-peptide gels using CATCH(+/-) (Co-Assembling Tags based on CHarge-complementarity) peptides.
• Recombinant fusion of enzymes to CATCH(-) peptides for integration into self-assembling β-sheet fibrils.
• In vivo evaluation of enzyme retention, catalytic activity, and therapeutic effects in disease models.

Main Results:

• Successful fabrication of catalytically active gels with NanoLuc luciferase, cutinase, uricase, and adenosine synthase A.
• Demonstrated prolonged tissue retention of CATCH(-)-NanoLuc gels compared to soluble enzyme.
• Resolved localized inflammation in a gout model using CATCH(-)-uricase gels and suppressed inflammation in response to lipopolysaccharide using CATCH(-)-adenosine synthase A gels.

Conclusions:

• CATCH enzyme-peptide gels provide a modular and tunable platform for local enzyme delivery.
• The system offers prolonged tissue retention, enhancing the effectiveness of local therapeutic biocatalysis.
• This approach represents a generalizable vehicle for advanced enzyme-based therapies.