Lipid Nanoparticle Systems for Enabling Gene Therapies.
By P. Cullis, M. Hope. Molecular Therapy, 2017
1,006 citations recorded by the source corpus.
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.
Subfields: Animal Science and Zoology, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/4c14295db1cc15e88bf7cfb2421f9b98f827eb85
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In Molecular Biology
Citations in the corpus
- Solid Lipid Nanoparticles for Drug Delivery: Pharmacological and Biopharmaceutical Aspects (2020, background): “…charged biomolecules like nucleic acids, lipids with a permanent positive charge tend to form complexes with nucleic acid polymers with limited or no in vivo utility due to their size (ca. 1 µm of diameter), instability, positive surface charge, and toxic side effects (Cullis and Hope, 2017).”
- Gene therapy clinical trials worldwide to 2017: An update (2018, background): “However, improvements to nucleic acid stability and potency, as well as lipid and polymer delivery technology, are advancing the field of nonviral gene delivery.(118-120) By contrast, viral systems, which are commonly modified to render them replication‐incompetent, are markedly more efficient and e”
- mRNA-based therapeutics: powerful and versatile tools to combat diseases (2022, background): “Nanoparticle materials achieve lysosome escape through conductivity, such as DOPE, MM27, and DLinDMA, which are widely applied to the cell membrane in an acid-mediated manner.(200,201,210) In addition, pH-responsive cell-penetrating peptides promoted endosome membrane disruption and enhanced protein”