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Integration of organoids in peptide drug discovery: rise of the high-throughput screening
  • +5
  • Siqi Zhang,
  • Jieting Shen,
  • Xingkai Wang,
  • Xiaona Sun,
  • Yuxuan Wu,
  • Ming-Rong Zhang,
  • Rui Wang,
  • hu kuan
Siqi Zhang
Chinese Academy of Medical Sciences & Peking Union Medical College Institute of Materia Medica
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Jieting Shen
Chinese Academy of Medical Sciences & Peking Union Medical College Institute of Materia Medica
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Xingkai Wang
Chinese Academy of Medical Sciences & Peking Union Medical College Institute of Materia Medica
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Xiaona Sun
Chinese Academy of Medical Sciences & Peking Union Medical College Institute of Materia Medica
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Yuxuan Wu
Chinese Academy of Medical Sciences & Peking Union Medical College Institute of Materia Medica
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Ming-Rong Zhang
National Institutes for Quantum and Technology Quantum Medical Science Directorate Institute for Quantum Medical Science
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Rui Wang
Chinese Academy of Medical Sciences & Peking Union Medical College Institute of Materia Medica
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hu kuan
Chinese Academy of Medical Sciences & Peking Union Medical College Institute of Materia Medica

Corresponding Author:hukuan@imm.ac.cn

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Abstract

Organoids are three-dimensional cell aggregates with near-physiologic cell behaviors and can undergo long-term expansion in vitro. They are amenable to high-throughput drug screening processes, which renders them a viable preclinical model for drug development. The procedure of organoid-based high-throughput screening has been extensively employed to discover small molecule drugs, encompassing the steps of generating organoids, examining efficient drugs in organoid cultures, and data assessment. Compared to small molecules, peptides are more straightforward to synthesize, can be modified chemically, and demonstrate a high degree of target specificity and low cytotoxicity. Therefore, they have emerged as promising carriers to deliver drugs to disease-associated targets, and could be efficient therapeutic drugs for various diseases. To date, organoids have been used to evaluate the efficacy of certain peptide agents; however, no organoid-based high-throughput screening of peptide drugs has been reported. Given the advantages of peptide drugs, there is an urgent need to establish organoid-based peptide high-throughput screening platforms. In this review, we discuss the typical approach of screening small-molecular drugs with the use of organoid cultures, as well as provide an overview of the studies that have incorporated organoids in peptide research. Drawing on the knowledge gained from small molecular screens, we explore the difficulties and potential avenues for creating new platforms to identify peptide agents using organoid models.
08 Feb 2023Submitted to View
10 Feb 2023Submission Checks Completed
10 Feb 2023Assigned to Editor
10 Feb 2023Review(s) Completed, Editorial Evaluation Pending
28 Feb 2023Reviewer(s) Assigned
21 Mar 2023Editorial Decision: Revise Major
27 May 20231st Revision Received
13 Jun 2023Submission Checks Completed
13 Jun 2023Assigned to Editor
13 Jun 2023Review(s) Completed, Editorial Evaluation Pending
13 Jun 2023Editorial Decision: Accept