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Candidate Gene Testing in Clinical Cohort Studies with Multiplexed Genotyping and Mass Spectrometry

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Published on: June 21, 2018

Drug development advances in human genetics-based targets.

Xiaoxia Zhang^1,2, Wenjun Yu³, Yan Li²

¹School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong Yantai University Yantai Shandong China.

|February 12, 2024

Summary

Human genetics and genomics accelerate drug discovery by validating targets. This review highlights eight beneficial loss-of-function mutation targets, aiding novel therapeutic development and drug repurposing.

Keywords:

drug development drug target genetic variation genome‐wide association studies whole‐exome sequencing whole‐genome sequencing

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Area of Science:

Genetics and Genomics
Drug Discovery and Development
Molecular Biology

Background:

Drug development is lengthy, costly, and uncertain.
Human genetic evidence can expedite clinical trials and drug approval.
Genetic technologies like GWAS, WES, and WGS identify disease-associated targets.

Purpose of the Study:

To review human genetics-based validated beneficial loss-of-function (LOF) mutation targets.
To discuss the feasibility, prospects, and challenges of eight specific LOF targets for drug discovery.
To encourage the use of human genetics in novel therapeutic discovery and clinical development.

Main Methods:

Review of scientific literature on human genetics and drug development.
Analysis of validated beneficial LOF mutation targets over the past decade.
Focus on eight specific targets: PCSK9, ANGPTL3, ASGR1, HSD17B13, KHK, CIDEB, GPR75, and INHBE.

Main Results:

Identified and validated numerous molecular targets using genetic data.
Detailed the structure, molecular biology, and drug development potential of beneficial LOF targets.
Assessed the feasibility of eight key LOF targets for therapeutic intervention.

Conclusions:

Human genetic evidence significantly de-risks and accelerates drug development.
Beneficial LOF mutation targets offer promising avenues for novel drug discovery.
This review aims to guide future research in genetics-driven drug discovery and repurposing.