Lipid nanoparticle technology for therapeutic gene regulation in the liver

Dominik Witzigmann, Jayesh A. Kulkarni, Jerry Leung, Sam Chen, Pieter R. Cullis (Corresponding author), Roy van der Meel

Research output: Contribution to journalReview articleAcademicpeer-review

2 Citations (Scopus)

Abstract

Hereditary genetic disorders, cancer, and infectious diseases of the liver affect millions of people around the globe and are a major public health burden. Most contemporary treatments offer limited relief as they generally aim to alleviate disease symptoms. Targeting the root cause of diseases originating in the liver by regulating malfunctioning genes with nucleic acid-based drugs s holds great promise as a therapeutic approach. However, employing nucleic acid therapeutics in vivo is challenging due to their unfavorable characteristics. Lipid nanoparticle (LNP) delivery technology is a revolutionary development that has enabled clinical translation of gene (editing) therapies. LNPs can deliver siRNA, mRNA, DNA, or gene-editing complexes, providing opportunities to treat hepatic diseases by silencing pathogenic genes, expressing therapeutic proteins, or correcting genetic defects. Here we discuss the state-of-the-art LNP technology for hepatic gene therapy including formulation design parameters, production methods, preclinical development and clinical translation.
Original languageEnglish
JournalAdvanced Drug Delivery Reviews
DOIs
Publication statusE-pub ahead of print - 2 Jul 2020

Keywords

  • CRISPR/Cas9
  • DNA
  • gene editing
  • gene expression
  • gene silencing
  • Gene therapy
  • guide RNA (gRNA)
  • hepatocyte
  • lipid nanoparticle (LNP)
  • lipids
  • liver
  • messenger RNA (mRNA)
  • small interfering RNA (siRNA)

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