Advancing drug discovery using the power of the human genome

Abstract

Human genetics plays an increasingly important role in drug development and population health. Here we review the history of human genetics in the context of accelerating the discovery of therapies, present examples of how human genetics evidence supports successful drug targets, and discuss how polygenic risk scores could be beneficial in various clinical settings. We highlight the value of direct‐to‐consumer platforms in the era of fast‐paced big data biotechnology, and how diverse genetic and health data can benefit society. © 2021 23andMe, Inc. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.

Nucleic Acid Drugs—Current Status, Issues, and Expectations for Exosomes

“…Another feature of nucleic acid drugs is that once a platform is established, it is possible to create a drug simply by changing the nucleotide sequence of the target gene; thus, rapid and efficient drug development can be expected. After sequencing of the human genome, the relationships between gene mutations and disease phenotypes are being unraveled with the progress in sequencing technology [ 6 , 7 ], and nucleic acid drugs are considered to meet this trend.…”

Biodistribution of Therapeutic Small Interfering RNAs Delivered with Lipid-Substituted Polyethylenimine-Based Delivery Systems

“…1 Advances in gene sequencing and gene therapy have allowed scientists to identify causative gene defects, or potential immunogens in the case of vaccines, and quickly develop therapies based on nucleic acids that are tailored for particular diseases. 2 The most well-known example of such an approach is the recent COVID-19 pandemic, where exogenous mRNA was used to instruct human cells to produce an immunogenic viral protein and therefore create long-term immunity in the vaccine recipients. 3 Alternatively, nucleic acids can also be used to reduce the production of a harmful protein when required.…”

“…During the last two decades, there has been a growing interest in therapeutic nucleic acids and their potential to become a central paradigm in the treatment or prevention of common diseases . Advances in gene sequencing and gene therapy have allowed scientists to identify causative gene defects, or potential immunogens in the case of vaccines, and quickly develop therapies based on nucleic acids that are tailored for particular diseases . The most well-known example of such an approach is the recent COVID-19 pandemic, where exogenous mRNA was used to instruct human cells to produce an immunogenic viral protein and therefore create long-term immunity in the vaccine recipients .…”

General Synthesis of Conformationally Constrained Noncanonical Amino Acids with C(sp3)-Rich Benzene Bioisosteres

“…The completion of the human genome project in the early 21st century marked the entry into the golden age of drug discovery, with the anticipation of confirming and understanding key disease-relevant targets to improve human health . Such opportunities also unveiled gaps between the complexity of these novel targets and our ability to achieve biological effects with traditional orally bioavailable small molecules (SMs) .…”