Using Genome Sequence to Enable the Design of Medicines and Chemical Probes

Chem Rev. 2018 Feb 28;118(4):1599-1663. doi: 10.1021/acs.chemrev.7b00504. Epub 2018 Jan 11.

Abstract

Rapid progress in genome sequencing technology has put us firmly into a postgenomic era. A key challenge in biomedical research is harnessing genome sequence to fulfill the promise of personalized medicine. This Review describes how genome sequencing has enabled the identification of disease-causing biomolecules and how these data have been converted into chemical probes of function, preclinical lead modalities, and ultimately U.S. Food and Drug Administration (FDA)-approved drugs. In particular, we focus on the use of oligonucleotide-based modalities to target disease-causing RNAs; small molecules that target DNA, RNA, or protein; the rational repurposing of known therapeutic modalities; and the advantages of pharmacogenetics. Lastly, we discuss the remaining challenges and opportunities in the direct utilization of genome sequence to enable design of medicines.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Cell Line, Tumor
  • Drug Repositioning
  • Genome, Human*
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Molecular Probes / chemistry*
  • Oligonucleotides / pharmacology
  • Oligonucleotides / therapeutic use
  • Pharmacogenetics
  • Proteins / drug effects
  • RNA / chemistry
  • Small Molecule Libraries
  • United States
  • United States Food and Drug Administration

Substances

  • Molecular Probes
  • Oligonucleotides
  • Proteins
  • Small Molecule Libraries
  • RNA