Thraustochytrid hosts for expression of proteins relevant to SARS-CoV-2 intervention

Copyright: © 2023 Dahmen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited..

The emergence of COVID-19 as a global pandemic had sharply illustrated the limitations of research and development pipelines and scaled manufacturing. Although existing vaccines were created in record time, global deployment remains limited by regional production scales. Similarly, the most effective treatments for infected COVID-19 patients are also constrained by production scales as well as by the cost of production and thus expense per treatment. The need to produce these interventions more cost-effectively, at larger scales, in less time while retaining high quality is paramount. The ConamaxTM platform is based on a Thraustochytrid-an order of microorganisms well established in industry for world-scale production of omega-3 fatty acids by fermentation. Thraustochytrids, and the species Aurantiochytrium acetophilum in particular, possess a number of innate qualities which make it ideal for production of monoclonal antibodies and other biotherapeutic proteins. In this study, the Conamax system was used to produce several targets which may be relevant as interventions in the fight against COVID-19; an anti-SARS-CoV-2 antibody (CR3022), tocilizumab, and the ACE2 receptor. Our system was capable of producing all of these targets and each was assayed in vitro for an activity which confirmed proper structural folding. Purified CR3022 antibody produced from Conamax was capable of reducing the cytopathic effect of SARS-CoV-2. Conamax-derived tocilizumab was shown to bind to its target IL6R. Both the full-length and soluble versions of ACE2 protein produced in the Conamax platform exhibited ACE2-specific proteolytic activity. These data indicate that the Conamax platform has great potential in the production of therapeutic agents.

Media Type:

Electronic Article

Year of Publication:

2023

Publication:

2023

Contained In:

To Main Record - volume:18

Contained In:

PloS one - 18(2023), 4 vom: 13., Seite e0283592

Language:

English

Contributors:

Dahmen, Jeremy [Author]
Vermeulen, Arjan [Author]
Payne, Sophie [Author]
Lippmeier, Casey [Author]

Links:

Volltext

Keywords:

Angiotensin-Converting Enzyme 2
Antibodies, Viral
EC 3.4.15.1
EC 3.4.17.23
Journal Article
Peptidyl-Dipeptidase A
Spike Glycoprotein, Coronavirus
Spike protein, SARS-CoV-2

Notes:

Date Completed 14.04.2023

Date Revised 18.04.2023

published: Electronic-eCollection

Citation Status MEDLINE

doi:

10.1371/journal.pone.0283592

funding:

Supporting institution / Project title:

PPN (Catalogue-ID):

NLM355479095