How Multimodal Screening Can Improve Drug Discovery and Development
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How Multimodal Screening Can Improve Drug Discovery and Development

Nyla Wolfe, Director of IT, Biogen

Nyla Wolfe, Director of IT, Biogen

This multimodal approach to screening has the ability to gather the total target space, bringing better drugs to the market faster.

Candidate attrition and late-phase failure are common problems in drug development. As screening is so important in identifying and validating targets, the quality of the screening technique used can be a determining factor in whether a new medicine reaches the clinic.

Even though gene-editing technologies like CRISPR and gene knockdown technologies like RNAi have shown promise, there's a chance that loss-of-function screening methods won't be able to detect the more subtle biological processes that influence clinical response. As a result, biotech and pharmaceutical companies are turning to new multimodal screening methodologies to find new drug-target interaction prospects.

Top 10 Drug Discovery and Development Solution Companies - 2020In cell culture systems, RNA interference (RNAi) was once considered the preferred method for target validation. Irrespective of the potential of RNA-based pooled screening and the enormous resources put in place to support it, intriguing candidates have failed to advance in clinical drug development.

Off-target effects, inaccurate results, and a reproducibility failure have all been attributed to the technique in subsequent investigations. As a result, RNAi-generated data is neither clean nor strong enough for industrial adoption. While screens with more repetitions and short hairpin RNAs (shRNAs) have yielded better positive results, more space exists for enhancement.

CRISPR screening has been demonstrated to be a more effective method of identifying targets. Compared to shRNA, the technical improvements for detection and statistical significance, along with a high effective rate from genetic ablation, enable researchers to observe significant phenotypic effects, enhancing efficiency.

With these restrictions in mind, researchers are now adopting a multimodal method to supplement the present drug discovery landscape, which has resulted in some exciting new developments. PROTEINi, a protein interference approach that has been used, is an example of this. Utilizing a phenotypic readout, PROTEINi can investigate and detect drug-mimetics in living cells on a large scale.

PROTEINi can expand the current target discovery space by detecting proteins and complexes that would otherwise be considered unsolvable. PROTEINi enables researchers to explore the biological activity that regulates regulatory pathways in greater depth than basic loss-of-function experiments because each responding therapeutic node can be examined.

Through carefully scanning the complete proteome to detect the most significant novel targets for drug development and, crucially, decide how to drug them, tools like these could unlock alternate, direct approaches to drug development.

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