Lipid Nanoparticle Systems for Enabling Gene Therapies
Open accessAbstract
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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- Authors
- Cullis, P. R., & Hope, M. J.
- Affiliations
- University of British Columbia (CA)
- Acuitas Therapeutics (Canada) (CA)
- Corresponding author
- Cullis, Pieter R.
- ORCID
- Cullis, Pieter R.
- Venue
- Molecular Therapy
- Publisher
- Elsevier BV
- Published
- 2017-07
- Volume
- 25
- Issue
- 7
- Pages
- 1467-1475
- ISSN
- 1525-0016 (ISSN-L)
- PMC
- PMC5498813
- OpenAlex
- W2600400434
- Cited by
- 1,208
- References
- 42
- Citations by year
- 2026: 214 · 2025: 198 · 2024: 196 · 2023: 169 · 2022: 147 · 2021: 118 · 2020: 73 · 2019: 51 · 2018: 26 · 2017: 14 · 2013: 1
- FWCI
- 4.19
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Molecular Therapy (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Canadian Institutes for Health Research
- Canadian Medical Research Council
- National Science and Engineering Research Council (NSERC)
- Genome BC
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advancements in Transdermal Drug Delivery
- Keywords
- lipid nanoparticles, gene therapy, siRNA delivery, mRNA delivery, plasmid DNA delivery, non-viral gene delivery, transthyretin amyloidosis, FDA approval, systemic administration, mRNA vaccines, genome editing, protein replacement therapy
- MeSH terms
- Animals, Antineoplastic Agents, Clinical Trials as Topic, Hepatitis B, Carcinoma, Hepatocellular, Humans, Lipids, Liver Neoplasms, Plasmids, RNA, Messenger, Genetic Therapy, Drug Delivery Systems, Hepatocytes, Amyloid Neuropathies, Familial, RNA, Small Interfering, Atherosclerosis, Nanoparticles
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