A group from University of Pennsylvania, Philadelphia, US, has proposed a gene therapy-based strategy to prevent COVID-19 using an ACE2-decoy protein encoded in an AAV vector delivered by nasal spray.
https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1009544
An affinity-matured ACE2 decoy achieving 1000-fold binding improvements across a wide range of SARS-CoV-2 variants has developed and fused with IgG4 Fc. The ACE-decoy as named CDY14-Fc as the most improved ACE2 decoy variant. The affinity maturation was done with using a diverse (>108 transformants) ACE2 variant libraries in a yeast-display format.
It was demonstrated that the CDY14-Fc could broadly neutralizes SARS-CoV-2 variants as follows. it seems that unlike antibodies, decoy inhibitors could achieve broader neutralization and escape mutant resistance; 501Y from B.1.1.7/alpha variant, 417N/484K/501Y from B1.351/beta variant, 452R/484Q from B.1.617.1/kappa variant, and so forth.
The goal in this strategy is to get decoy proteins expressed internasal delivering the decoy genes with AAV vectors by nasal spray. This idea was confirmed by in vivo experiments with nonhuman primates.
