Related Experiment Video
Updated: Jul 27, 2025
07:16
Author Spotlight: Advancements in DNA Nanosensors – Addressing Sensitivity and Selectivity Challenges in Molecular Detection
Published on: February 9, 2024
1.0K
Targeting NETs using dual-active DNase1 variants
Hanna Englert1, Josephine Göbel1, Danika Khong1
1Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Frontiers in Immunology
|June 8, 2023
Summary
Engineered a dual-acting DNase enzyme combining DNase1 and DNase1L3 activities to effectively degrade Neutrophil Extracellular Traps (NETs). This dual-active DNase shows promise for treating thromboinflammatory diseases by neutralizing DNA and NETs.
Area of Science:
- Biochemistry
- Molecular Biology
- Immunology
Background:
- Neutrophil Extracellular Traps (NETs) are implicated in various diseases due to impaired clearance.
- Efficient NET degradation relies on DNase1 and DNase1-like 3 (DNase1L3) enzymes.
Purpose of the Study:
- To engineer a dual-active DNase with combined DNase1 and DNase1L3 functions.
- To evaluate the NET-degrading potential of the engineered enzyme.
Main Methods:
- Engineered a dual-active DNase by substituting DNase1 amino acid stretches with DNase1L3 sequences.
- Produced transgenic mice expressing the dual-active DNase.
- Assessed enzyme activity in mouse body fluids.
Main Results:
- Identified key DNase1L3 regions for chromatin degradation.
- Created a dual-active DNase1 mutant superior to native enzymes in degrading dsDNA and chromatin.
- Demonstrated stability and circulation of the mutant enzyme in vivo.
Conclusions:
- The dual-active DNase1 mutant effectively degrades dsDNA and chromatin.
- This engineered enzyme is a potential therapeutic agent for thromboinflammatory diseases.
