Development of nucleic acid medicines based on chemical technology

Yusuke Kawamoto; You Wu; Yuki Takahashi; Yoshinobu Takakura

doi:10.1016/j.addr.2023.114872

Development of nucleic acid medicines based on chemical technology

Adv Drug Deliv Rev. 2023 Aug:199:114872. doi: 10.1016/j.addr.2023.114872. Epub 2023 May 25.

Authors

Yusuke Kawamoto¹, You Wu², Yuki Takahashi², Yoshinobu Takakura³

Affiliations

¹ Department of Biopharmaceutics and Drug Metabolism, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo, Kyoto 606-8501, Japan. Electronic address: y.kawamoto@pharm.kyoto-u.ac.jp.
² Department of Biopharmaceutics and Drug Metabolism, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo, Kyoto 606-8501, Japan.
³ Department of Biopharmaceutics and Drug Metabolism, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo, Kyoto 606-8501, Japan. Electronic address: takakura@pharm.kyoto-u.ac.jp.

PMID: 37244354
DOI: 10.1016/j.addr.2023.114872

Abstract

Oligonucleotide-based therapeutics have attracted attention as an emerging modality that includes the modulation of genes and their binding proteins related to diseases, allowing us to take action on previously undruggable targets. Since the late 2010s, the number of oligonucleotide medicines approved for clinical uses has dramatically increased. Various chemistry-based technologies have been developed to improve the therapeutic properties of oligonucleotides, such as chemical modification, conjugation, and nanoparticle formation, which can increase nuclease resistance, enhance affinity and selectivity to target sites, suppress off-target effects, and improve pharmacokinetic properties. Similar strategies employing modified nucleobases and lipid nanoparticles have been used for developing coronavirus disease 2019 mRNA vaccines. In this review, we provide an overview of the development of chemistry-based technologies aimed at using nucleic acids for developing therapeutics over the past several decades, with a specific emphasis on the structural design and functionality of chemical modification strategies.

Keywords: Bioconjugations; Cellular uptake; Chemical modifications; Nanoparticles; Therapeutic oligonucleotides; Tissue-selective delivery; mRNA vaccines.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

COVID-19*
Humans
Nucleic Acids*
Oligonucleotides / chemistry
Oligonucleotides, Antisense
Technology

Substances

Nucleic Acids
Oligonucleotides
Oligonucleotides, Antisense