. 2023 Oct 3;228(Suppl 5):S337-S354.

doi: 10.1093/infdis/jiad334.

Report of the Assay Guidance Workshop on 3-Dimensional Tissue Models for Antiviral Drug Development

Robert Jordan¹, Stephanie L Ford-Scheimer², Rodolfo M Alarcon³, Anthony Atala⁴, Jeffrey T Borenstein⁵, Kyle R Brimacombe², Sara Cherry⁶, Hans Clevers⁷, Mindy I Davis³, Simon G P Funnell^{8

9}, Lee Gehrke^{10

11}, Linda G Griffith^{12

13}, Abigail C Grossman², Thomas Hartung^{14

15}, Donald E Ingber^{11

16

17

18}, Nicole C Kleinstreuer¹⁹, Calvin J Kuo²⁰, Emily M Lee², Christine L Mummery²¹, Thames E Pickett³, Sasirekha Ramani²², Edwin A Rosado-Olivieri²³, Evi B Struble²⁴, Zhengpeng Wan¹², Mark S Williams³, Matthew D Hall², Marc Ferrer², Sarine Markossian²

Affiliations

¹ Bill and Melinda Gates Foundation, Seattle, Washington, USA.
² National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland, USA.
³ National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
⁴ Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
⁵ Draper Laboratory, Cambridge, Massachusetts, USA.
⁶ Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
⁷ Hubrecht Institute, Utrecht, The Netherlands.
⁸ UK Health Security Agency, Salisbury, United Kingdom.
⁹ Quadram Institute Bioscience, Norwich, United Kingdom.
¹⁰ Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
¹¹ Harvard Medical School, Boston, Massachusetts, USA.
¹² Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
¹³ Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
¹⁴ Department of Environmental Health and Engineering, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA.
¹⁵ Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA.
¹⁶ Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts, USA.
¹⁷ Harvard School of Engineering and Applied Sciences, Cambridge, Massachusetts, USA.
¹⁸ Boston Children's Hospital, Boston, Massachusetts, USA.
¹⁹ National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle, North Carolina, USA.
²⁰ Department of Medicine, Division of Hematology, Stanford University School of Medicine, Stanford, California, USA.
²¹ Leiden University Medical Center, Leiden, The Netherlands.
²² Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USA.
²³ RumiViro, RUMI Scientific, Inc, New York, New York, USA.
²⁴ US Food and Drug Administration, Silver Spring, Maryland, USA.

PMID: 37669225
PMCID: PMC10547463
DOI: 10.1093/infdis/jiad334

Report of the Assay Guidance Workshop on 3-Dimensional Tissue Models for Antiviral Drug Development

Robert Jordan et al. J Infect Dis. 2023.

. 2023 Oct 3;228(Suppl 5):S337-S354.

doi: 10.1093/infdis/jiad334.

Authors

Affiliations

¹ Bill and Melinda Gates Foundation, Seattle, Washington, USA.
² National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland, USA.
³ National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
⁴ Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
⁵ Draper Laboratory, Cambridge, Massachusetts, USA.
⁶ Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
⁷ Hubrecht Institute, Utrecht, The Netherlands.
⁸ UK Health Security Agency, Salisbury, United Kingdom.
⁹ Quadram Institute Bioscience, Norwich, United Kingdom.
¹⁰ Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
¹¹ Harvard Medical School, Boston, Massachusetts, USA.
¹² Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
¹³ Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
¹⁴ Department of Environmental Health and Engineering, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA.
¹⁵ Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA.
¹⁶ Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts, USA.
¹⁷ Harvard School of Engineering and Applied Sciences, Cambridge, Massachusetts, USA.
¹⁸ Boston Children's Hospital, Boston, Massachusetts, USA.
¹⁹ National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle, North Carolina, USA.
²⁰ Department of Medicine, Division of Hematology, Stanford University School of Medicine, Stanford, California, USA.
²¹ Leiden University Medical Center, Leiden, The Netherlands.
²² Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USA.
²³ RumiViro, RUMI Scientific, Inc, New York, New York, USA.
²⁴ US Food and Drug Administration, Silver Spring, Maryland, USA.

PMID: 37669225
PMCID: PMC10547463
DOI: 10.1093/infdis/jiad334

Abstract

The National Center for Advancing Translational Sciences (NCATS) Assay Guidance Manual (AGM) Workshop on 3D Tissue Models for Antiviral Drug Development, held virtually on 7-8 June 2022, provided comprehensive coverage of critical concepts intended to help scientists establish robust, reproducible, and scalable 3D tissue models to study viruses with pandemic potential. This workshop was organized by NCATS, the National Institute of Allergy and Infectious Diseases, and the Bill and Melinda Gates Foundation. During the workshop, scientific experts from academia, industry, and government provided an overview of 3D tissue models' utility and limitations, use of existing 3D tissue models for antiviral drug development, practical advice, best practices, and case studies about the application of available 3D tissue models to infectious disease modeling. This report includes a summary of each workshop session as well as a discussion of perspectives and challenges related to the use of 3D tissues in antiviral drug discovery.

Keywords: 3D tissue models; SARS-CoV-2; antiviral drug discovery; body-on-a-chip; human pluripotent stem cells (hPSCs); induced pluripotent stem cells (iPSCs); microphysiological systems (MPS); organ-on-a-chip; organoid; tissue-derived stem cells.

Published by Oxford University Press on behalf of Infectious Diseases Society of America 2023.

PubMed Disclaimer

Conflict of interest statement

Potential conflicts of interest. A. A. is a shareholder in Biorg, Inc (Winston-Salem, NC). D. E. I. is a shareholder in Emulate, Inc (Boston, MA). E. A. R. is a shareholder in RUMI Viro, Inc and RUMI Scientific, Inc (New York, NY). T. H. is a shareholder in AxoSim, LLC (New Orleans, LA). All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Figures

**Figure 1.**
Scheme showing various three-dimensional (3D) tissue models used in preclinical research spanning from low to high complexity. 3D tissue models vary substantially with respect to design, throughput, complexity, and physiological relevance. Physiological complexity and relevance usually contrast assay throughput. Session 1 of this workshop covered a variety of tissue models spanning from organoids to body-on-a-chip systems, and discussed their utility and limitations for drug screening. Figure created with BioRender.com.

**Figure 2.**
Scheme showing how three-dimensional (3D) tissue models are incorporated into the antiviral development pipeline. Disease modeling with 3D tissue models (organoids, organ-on-a-chip, etc.) is essential for target identification purposes. 3D models of infection can also be incorporated in drug screening and lead optimization stages of the pipeline. Toxicology predictions using body-on-chip models could also be performed. Sessions 1–3 of this workshop presented multiple case studies on how these 3D models of infection have been incorporated into the antiviral drug discovery pipeline. Figure created with BioRender.com.

See this image and copyright information in PMC

References

1. Markossian S, Brimacombe KR, Sittampalam GS, et al. . The NCATS assay guidance manual programme: advancing the practice and rigour of preclinical translation. Nat Rev Drug Discov 2022; 21:863–4. - PubMed
1. Wikswo JP. The relevance and potential roles of microphysiological systems in biology and medicine. Exp Biol Med (Maywood) 2014; 239:1061–72. - PMC - PubMed
1. Wadman M. FDA no longer has to require animal testing for new drugs. Science 2023; 379:127–8. - PubMed
1. Funnell SGP, Dowling WE, Muñoz-Fontela C, et al. . Emerging preclinical evidence does not support broad use of hydroxychloroquine in COVID-19 patients. Nat Commun 2020; 11:4253. - PMC - PubMed
1. Armando F, Beythien G, Kaiser FK, et al. . SARS-CoV-2 Omicron variant causes mild pathology in the upper and lower respiratory tract of hamsters. Nat Commun 2022; 13:3519. - PMC - PubMed

Publication types

Actions

MeSH terms

Actions
Actions
Actions
Actions

Substances

Actions

LinkOut - more resources

Full Text Sources
Miscellaneous
- NCI CPTAC Assay Portal

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Report of the Assay Guidance Workshop on 3-Dimensional Tissue Models for Antiviral Drug Development

Affiliations

Report of the Assay Guidance Workshop on 3-Dimensional Tissue Models for Antiviral Drug Development

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Substances

LinkOut - more resources

Full Text Sources

Miscellaneous