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Genetic screens are tools used to identify genes and mutations responsible for phenotypes of interest. Genetic screens help identify individuals or a group of people at risk of developing genetic diseases and help them with early intervention, targeted therapy, and reproductive options.
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Perspectives on phenotypic screening-Screen Design and Assay Technology Special Interest Group.

Chorom Pak¹, Kaylene J Simpson², Andrea D Weston³

¹Lynx Biosciences, Inc., 3210 Merryfield Row, San Diego, CA, USA.

SLAS Discovery : Advancing Life Sciences R & D

|February 4, 2024

Summary

Phenotypic screening shows promise for drug discovery but faces challenges. Addressing these requires strategic planning, advanced models, and robust data analysis for better clinical translation.

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Area of Science:

Drug discovery and development
Pharmacology
Biotechnology

Background:

Phenotypic screening is crucial for early drug discovery, aiming to translate disease-relevant findings into clinical success.
Despite progress, significant operational and scientific hurdles impede the implementation and translation of phenotypic screening efforts.

Purpose of the Study:

To assess the current state of phenotypic screening in drug discovery.
To identify and discuss challenges and potential solutions for improving the translation of screening hits.
To offer perspectives on enhancing disease relevance in early drug discovery through phenotypic screening.

Main Methods:

The study is based on discussions from the "Phenotypic screening, target ID, and multi-omics: enabling more disease relevance in early discovery?" session at the 2023 SLAS Conference.
Expert perspectives from various organizations were shared, followed by audience discussion.
Key areas explored include screening strategy, cellular models, 3D cultures, and high-dimensional data analysis.

Main Results:

Substantial progress has been made, yet significant challenges remain in phenotypic screening implementation.
Improving translation of screening hits demands considerable resources and organizational commitment.
Key areas for improvement include screening strategy, cellular model selection, 3D culture adoption, and leveraging multi-omics data.

Conclusions:

Phenotypic drug discovery holds therapeutic potential that can be unlocked by addressing current limitations.
Strategic approaches to screening, validation, and data utilization are essential for success.
Overcoming operational and scientific challenges is key to improving the clinical translation of phenotypic screening findings.