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COMMENTARY
Organoids as a platform for personalized antisense

oligonucleotide screening: Advancing precision
medicine

Xufeng Wan, Zongke Zhou, and Duan Wang*
Department of Orthopedics, Orthopedic Research Institute, West China Hospital, Sichuan University, Chengdu, Sichuan, China
*Corresponding author: Duan Wang (wangduan@wchscu.cn)

Citation: Wan X, Zhou Z, Abstract
Wang D. Organoids as a platform
for personalized antisense
oligonucleotide screening: Advancing Organoid technology has transformed precision medicine by enabling patient-
precision medicine. Organoid Res. specific 3D models that replicate tissue complexity, facilitating high-throughput
2025;1(3):025120012. antisense oligonucleotide (ASO) therapeutic screening. Patient-derived organoids
doi: 10.36922/OR025120012 retain donor-specific genetic and phenotypic profiles, offering physiologically
Received: March 21, 2025 relevant platforms for modeling diseases, such as Duchenne muscular dystrophy
Revised: April 29, 2025 (DMD). For example, DMD cardiac organoids rapidly identify dystrophin-restoring
ASOs through a 6-week validation pipeline, overcoming limitations of 2D cultures
Accepted: May 16, 2025 by preserving multicellular interactions. Challenges include expanding tissue
Published online: June 6, 2025 representation (e.g., skeletal muscle in DMD), enhancing ASO pharmacokinetic
Copyright: © 2025 Author(s). modeling in avascular organoids, and standardizing protocols to minimize
This is an Open-Access article variability. Future integration of vascularized or organ-on-chip models, multi-tissue
distributed under the terms of the assembloids, and artificial intelligence-driven screening could improve predictive
Creative Commons Attribution
License, permitting distribution, and accuracy. Chemically optimized ASOs with reduced off-target effects, combined
reproduction in any medium, which with clustered regularly interspaced short palindromic repeats-based editing, may
provided that the original work is synergistically enhance therapeutic precision. As regulatory frameworks adapt to
properly cited.
incorporate organoid-based validation, this technology accelerates personalized
Publisher’s Note: AccScience drug discovery for genetic disorders. Addressing present limitations through
Publishing remains neutral with regard
to jurisdictional claims in published bioengineering and standardization will solidify organoids as critical tools for
maps and institutional affiliations. tailoring precision therapies to individual patient needs.

Keywords: Organoids; Antisense oligonucleotides; Personalized drug screening

The advent of organoid technology has fundamentally impactful applications of organoid technology is its role
transformed biomedical research by providing three- in disease modeling, particularly in genetic disorders
dimensional (3D) models that closely replicate the where patient-derived organoids (PDOs) serve as high-
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intricate architecture and function of human tissues. fidelity pre-clinical platforms for evaluating individualized
Conventional two-dimensional (2D) cell cultures, though therapeutic strategies. These organoids retain the genetic,
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widely utilized, fail to capture the complex cellular molecular, and phenotypic characteristics of their
interactions inherent to native tissue environments, while donor tissue, making them highly relevant for studying
animal models, despite their physiological relevance, pathogenic mutations, transcriptomic alterations, and
often exhibit species-specific differences that limit their drug responses. Antisense oligonucleotide (ASO) therapies
translational value. Organoids bridge this gap by self- hold transformative potential for treating genetic disorders
organizing into miniature, organ-like structures, allowing by directly targeting disease-causing RNA, yet their
for precise investigation into tissue development, disease development is hindered by the lack of pre-clinical models
pathogenesis, and therapeutic interventions within a that accurately reflect patient-specific genetic diversity
controlled, patient-specific framework. Among the most and tissue complexity. Conventional screening platforms
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Volume 1 Issue 3 (2025) 1 doi: 10.36922/OR025120012