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Lipid Nanoparticle Systems for Enabling Gene Therapies.

Authors
  • Cullis, Pieter R1
  • Hope, Michael J2
  • 1 Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, BC V6T 1Z3, Canada. Electronic address: [email protected] , (Canada)
  • 2 Acuitas Therapeutics, Vancouver, BC V6T 1Z3, Canada. , (Canada)
Type
Published Article
Journal
Molecular Therapy
Publisher
Elsevier
Publication Date
Jul 05, 2017
Volume
25
Issue
7
Pages
1467–1475
Identifiers
DOI: 10.1016/j.ymthe.2017.03.013
PMID: 28412170
Source
Medline
Keywords
License
Unknown

Abstract

Genetic drugs such as small interfering RNA (siRNA), mRNA, or plasmid DNA provide potential gene therapies to treat most diseases by silencing pathological genes, expressing therapeutic proteins, or through gene-editing applications. In order for genetic drugs to be used clinically, however, sophisticated delivery systems are required. Lipid nanoparticle (LNP) systems are currently the lead non-viral delivery systems for enabling the clinical potential of genetic drugs. Application will be made to the Food and Drug Administration (FDA) in 2017 for approval of an LNP siRNA drug to treat transthyretin-induced amyloidosis, presently an untreatable disease. Here, we first review research leading to the development of LNP siRNA systems capable of silencing target genes in hepatocytes following systemic administration. Subsequently, progress made to extend LNP technology to mRNA and plasmids for protein replacement, vaccine, and gene-editing applications is summarized. Finally, we address current limitations of LNP technology as applied to genetic drugs and ways in which such limitations may be overcome. It is concluded that LNP technology, by virtue of robust and efficient formulation processes, as well as advantages in potency, payload, and design flexibility, will be a dominant non-viral technology to enable the enormous potential of gene therapy.

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