An albumin-angiotensin converting enzyme 2-based SARS-CoV-2 decoy with FcRn-driven half-life extension

Elisabeth Fuchs
Aarhus University
January 1, 2022
Acta Biomater
https://pubmed.ncbi.nlm.nih.gov/36162760

This article is currently being updated. View its version on PubMed.

https://pubmed.ncbi.nlm.nih.gov/36162760

Research summary

This study presents a recombinant human albumin-ACE2 fusion protein (rHA-ACE2) designed to act as a decoy receptor for SARS-CoV-2, aiming to extend plasma half-life via FcRn-mediated recycling. Two variants were developed: one with wild-type albumin (WT-ACE2) and another with mutations abolishing FcRn binding (NB-ACE2). Both variants demonstrated binding to the SARS-CoV-2 spike protein and inhibited viral entry in vitro. In humanized FcRn/albumin double transgenic mice, WT-ACE2 exhibited a fivefold increase in plasma half-life compared to soluble ACE2, highlighting the role of FcRn in prolonging circulation time.

Key outcome of the study

The rHA-ACE2 fusion protein effectively binds SARS-CoV-2 spike protein and inhibits viral entry in vitro. In vivo studies in humanized mice demonstrate that FcRn-mediated recycling significantly extends the plasma half-life of WT-ACE2, suggesting potential for improved therapeutic efficacy against COVID-19.

Mouse model

Humanized FcRn/albumin double transgenic mice, engineered to express human neonatal Fc receptor (FcRn) and human albumin, enabling accurate assessment of FcRn-mediated recycling and pharmacokinetics of albumin-based therapeutics.

TARGET:
ACE2
Angiotensin-converting enzyme 2

Keywords

COVID-19, SARS-CoV-2, ACE2 decoy, Albumin fusion protein, FcRn-mediated recycling, Antiviral therapeutics

Technical specifications

Transgenic mouse model, Humanized FcRn expression, Human albumin expression, Pharmacokinetics assessment, FcRn binding studies

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