Design of lipid-based nanoparticles for delivery of therapeutic nucleic acids

Monique C P Mendonça; Ayse Kont; Piotr S Kowalski; Caitriona M O'Driscoll

doi:10.1016/j.drudis.2023.103505

Design of lipid-based nanoparticles for delivery of therapeutic nucleic acids

Drug Discov Today. 2023 Mar;28(3):103505. doi: 10.1016/j.drudis.2023.103505. Epub 2023 Jan 25.

Authors

Monique C P Mendonça¹, Ayse Kont¹, Piotr S Kowalski¹, Caitriona M O'Driscoll²

Affiliations

¹ School of Pharmacy, University College Cork, T12 YT20 Cork, Ireland.
² School of Pharmacy, University College Cork, T12 YT20 Cork, Ireland. Electronic address: caitriona.odriscoll@ucc.ie.

PMID: 36708760
DOI: 10.1016/j.drudis.2023.103505

Abstract

The successful development of nonviral delivery systems for nucleic acids has been reported extensively over the past number of years. Among them, lipid-based nanoparticles (LNPs) represent the most advanced platform. This review provides an overview of the state-of-the-art in LNP technology, focusing on the delivery of a range of nucleic acids. Recent advances in the development of an efficient and safe lipid-based system are critically analyzed with a particular emphasis on the rationale behind the design of LNPs and on attempts to elucidate the resulting molecular assembly and structure, their interactions with cellular proteins and biodistribution. In addition, manufacturing methods including microfluidics and their potential to influence stability and scale-up are summarized.

Keywords: Gene therapy; lipid excipients; mRNA; non-viral delivery; siRNA.

Publication types

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

MeSH terms

Lipids / chemistry
Microfluidics
Nanoparticles* / chemistry
Nucleic Acids*
RNA, Small Interfering
Tissue Distribution

Substances

Nucleic Acids
Lipids
RNA, Small Interfering