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Integrated autolysis, DNA hydrolysis and precipitation enables an improved bioprocess for Q-Griffithsin, a broad-spectrum antiviral and clinical-stage anti-COVID-19 candidate.

Publication ,  Journal Article
Decker, JS; Menacho-Melgar, R; Lynch, MD
Published in: Biochemical engineering journal
April 2022

Across the biomanufacturing industry, innovations are needed to improve efficiency and flexibility, especially in the face of challenges such as the COVID-19 pandemic. Here we report an improved bioprocess for Q-Griffithsin, a broad-spectrum antiviral currently in clinical trials for COVID-19. Q-Griffithsin is produced at high titer in E. coli and purified to anticipated clinical grade without conventional chromatography or the need for any fixed downstream equipment. The process is thus both low-cost and highly flexible, facilitating low sales prices and agile modifications of production capacity, two key features for pandemic response. The simplicity of this process is enabled by a novel unit operation that integrates cellular autolysis, autohydrolysis of nucleic acids, and contaminant precipitation, giving essentially complete removal of host cell DNA as well as reducing host cell proteins and endotoxin by 3.6 and 2.4 log10 units, respectively. This unit operation can be performed rapidly and in the fermentation vessel, such that Q-GRFT is obtained with 100% yield and > 99.9% purity immediately after fermentation and requires only a flow-through membrane chromatography step for further contaminant removal. Using this operation or variations of it may enable improved bioprocesses for a range of other high-value proteins in E. coli.

Duke Scholars

Published In

Biochemical engineering journal

DOI

ISSN

1369-703X

Publication Date

April 2022

Volume

181

Start / End Page

108403

Related Subject Headings

  • Biotechnology
  • 4004 Chemical engineering
  • 3106 Industrial biotechnology
  • 1003 Industrial Biotechnology
  • 0904 Chemical Engineering
  • 0601 Biochemistry and Cell Biology
 

Citation

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Decker, J. S., Menacho-Melgar, R., & Lynch, M. D. (2022). Integrated autolysis, DNA hydrolysis and precipitation enables an improved bioprocess for Q-Griffithsin, a broad-spectrum antiviral and clinical-stage anti-COVID-19 candidate. Biochemical Engineering Journal, 181, 108403. https://doi.org/10.1016/j.bej.2022.108403
Decker, John S., Romel Menacho-Melgar, and Michael D. Lynch. “Integrated autolysis, DNA hydrolysis and precipitation enables an improved bioprocess for Q-Griffithsin, a broad-spectrum antiviral and clinical-stage anti-COVID-19 candidate.Biochemical Engineering Journal 181 (April 2022): 108403. https://doi.org/10.1016/j.bej.2022.108403.
Decker, John S., et al. “Integrated autolysis, DNA hydrolysis and precipitation enables an improved bioprocess for Q-Griffithsin, a broad-spectrum antiviral and clinical-stage anti-COVID-19 candidate.Biochemical Engineering Journal, vol. 181, Apr. 2022, p. 108403. Epmc, doi:10.1016/j.bej.2022.108403.
Journal cover image

Published In

Biochemical engineering journal

DOI

ISSN

1369-703X

Publication Date

April 2022

Volume

181

Start / End Page

108403

Related Subject Headings

  • Biotechnology
  • 4004 Chemical engineering
  • 3106 Industrial biotechnology
  • 1003 Industrial Biotechnology
  • 0904 Chemical Engineering
  • 0601 Biochemistry and Cell Biology