Integration of organoids in peptide drug discovery: rise of the
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.