Data di Pubblicazione:
2021
Citazione:
Advancing Drug Discovery for Neurological Disorders Using iPSC-Derived Neural Organoids / G. Costamagna, G.P. Comi, S. Corti. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1422-0067. - 22:5(2021 Mar 06), pp. 2659.1-2659.21. [10.3390/ijms22052659]
Abstract:
In the last decade, different research groups in the academic setting have developed induced pluripotent stem cell-based protocols to generate three-dimensional, multicellular, neural organoids. Their use to model brain biology, early neural development, and human diseases has provided new insights into the pathophysiology of neuropsychiatric and neurological disorders, including microcephaly, autism, Parkinson's disease, and Alzheimer's disease. However, the adoption of organoid technology for large-scale drug screening in the industry has been hampered by challenges with reproducibility, scalability, and translatability to human disease. Potential technical solutions to expand their use in drug discovery pipelines include Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) to create isogenic models, single-cell RNA sequencing to characterize the model at a cellular level, and machine learning to analyze complex data sets. In addition, high-content imaging, automated liquid handling, and standardized assays represent other valuable tools toward this goal. Though several open issues still hamper the full implementation of the organoid technology outside academia, rapid progress in this field will help to prompt its translation toward large-scale drug screening for neurological disorders.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
CRISPR-Cas9; bioengineering; brain organoids; disease modeling; drug discovery; induced pluripotent stem cells (iPSCs); machine learning; neurological diseases; organoid imaging; single-cell sequencing; Animals; Automation; Brain; CRISPR-Cas Systems; Cell Culture Techniques; Collagen; Drug Combinations; Drug Discovery; Drug Evaluation, Preclinical; Drug Industry; Forecasting; High-Throughput Screening Assays; Humans; Induced Pluripotent Stem Cells; Laminin; Machine Learning; Microscopy; Nervous System Diseases; Organoids; Proteoglycans; RNA-Seq; Reproducibility of Results; Single-Cell Analysis
Elenco autori:
G. Costamagna, G.P. Comi, S. Corti
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