Integration of organoids in peptide drug discovery: Rise of the high‐throughput screening

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‐bas...

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Main Authors: Siqi Zhang, Jieting Shen, Xingkai Wang, Xiaona Sun, Yuxuan Wu, Ming‐Rong Zhang, Rui Wang, Kuan Hu
Format: Article
Language:English
Published: Wiley 2023-12-01
Series:View
Subjects:
Online Access:https://doi.org/10.1002/VIW.20230010
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author Siqi Zhang
Jieting Shen
Xingkai Wang
Xiaona Sun
Yuxuan Wu
Ming‐Rong Zhang
Rui Wang
Kuan Hu
author_facet Siqi Zhang
Jieting Shen
Xingkai Wang
Xiaona Sun
Yuxuan Wu
Ming‐Rong Zhang
Rui Wang
Kuan Hu
author_sort Siqi Zhang
collection DOAJ
description 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 high 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 from small molecular screens, we explore the difficulties and potential avenues for creating new platforms to identify peptide agents using organoid models.
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spelling doaj.art-599303c6004f4976ac6b8f7fcff4ccee2023-12-21T10:46:40ZengWileyView2688-39882688-268X2023-12-0146n/an/a10.1002/VIW.20230010Integration of organoids in peptide drug discovery: Rise of the high‐throughput screeningSiqi Zhang0Jieting Shen1Xingkai Wang2Xiaona Sun3Yuxuan Wu4Ming‐Rong Zhang5Rui Wang6Kuan Hu7State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical College BeijingChinaState Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical College BeijingChinaState Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical College BeijingChinaState Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical College BeijingChinaState Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical College BeijingChinaDepartment of Advanced Nuclear Medicine Sciences Institute of Quantum Medical Science National Institutes for Quantum Science and Technology ChibaJapanState Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical College BeijingChinaState Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical College BeijingChinaAbstract 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 high 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 from small molecular screens, we explore the difficulties and potential avenues for creating new platforms to identify peptide agents using organoid models.https://doi.org/10.1002/VIW.20230010high‐throughput screeningorganoidspeptide‐based radiopharmaceuticalspeptide–drug conjugatestherapeutic peptides
spellingShingle Siqi Zhang
Jieting Shen
Xingkai Wang
Xiaona Sun
Yuxuan Wu
Ming‐Rong Zhang
Rui Wang
Kuan Hu
Integration of organoids in peptide drug discovery: Rise of the high‐throughput screening
View
high‐throughput screening
organoids
peptide‐based radiopharmaceuticals
peptide–drug conjugates
therapeutic peptides
title Integration of organoids in peptide drug discovery: Rise of the high‐throughput screening
title_full Integration of organoids in peptide drug discovery: Rise of the high‐throughput screening
title_fullStr Integration of organoids in peptide drug discovery: Rise of the high‐throughput screening
title_full_unstemmed Integration of organoids in peptide drug discovery: Rise of the high‐throughput screening
title_short Integration of organoids in peptide drug discovery: Rise of the high‐throughput screening
title_sort integration of organoids in peptide drug discovery rise of the high throughput screening
topic high‐throughput screening
organoids
peptide‐based radiopharmaceuticals
peptide–drug conjugates
therapeutic peptides
url https://doi.org/10.1002/VIW.20230010
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