Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2016 Jul 5:11:3077-86.
doi: 10.2147/IJN.S106625. eCollection 2016.

Lipid nanoparticles for targeted siRNA delivery - going from bench to bedside

Timofei S Zatsepin  1 , Yuri V Kotelevtsev  2 , Victor Koteliansky  3
Affiliations
Review

Lipid nanoparticles for targeted siRNA delivery - going from bench to bedside

Timofei S Zatsepin et al. Int J Nanomedicine. .

Abstract

This review covers the basic aspects of small interfering RNA delivery by lipid nano-particles (LNPs) and elaborates on the current status of clinical trials for these systems. We briefly describe the roles of all LNP components and possible strategies for their improvement. We also focus on the current clinical trials using LNP-formulated RNA and the possible outcomes for therapy in the near future. Also, we present a critical analysis of selected clinical trials that reveals the common logic behind target selection. We address this review to a wide audience, especially to medical doctors who are interested in the application of RNA interference-based treatment platforms. We anticipate that this review may spark interest in this particular audience and generate new ideas in target selection for the disorders they are dealing with.

Keywords: RNA therapeutics; clinical trial; lipid nanoparticle; mRNA; siRNA; targeted delivery.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Structures of lipids used for RNA delivery. Notes: (A) Cationic lipids and lipidoids. (B) Phospholipids. (C) PEG lipids, cholesterol. Abbreviations: DOPC, 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine; PEG, polyethylene glycol; DOTAP, 1,2-dioleoyl-3-trimethylammonium-propane; DSPC, 1,2-distearoyl-sn-glycero-3-phosphocholine; PEG-C-DMA, 3-N-[(ω-methoxypoly(ethylene glycol)2000)carbamoyl]-1,2-dimyristyloxy-propylamine; mPEG-DSPE, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000].
Figure 2
Figure 2
Schematic structure of lipid nanoparticles. Abbreviation: PEG, polyethylene glycol.
Figure 3
Figure 3
Structures of modified RNA.
See this image and copyright information in PMC

References

    1. Vinores SA. Pegaptanib in the treatment of wet, age-related macular degeneration. Int J Nanomedicine. 2006;1(3):263–268. - PMC - PubMed
    1. U.S. Food and Drug Administration FDA Approves New Drug Treatment for Age-Related Macular Degeneration [press release] 2004. [Accessed December 1, 2015]. [December 20]. Available from: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2004/ucm108385....
    1. Tse MT. Regulatory watch: Antisense approval provides boost to the field. Nature Rev Drug Disc. 2013;12:179.
    1. U.S. Food and Drug Administration FDA approves new orphan drug Kynamro to treat inherited cholesterol disorder [press release] 2013. [Accessed December 1, 2015]. [January 29]. Available from: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm337195.htm.
    1. Zuckerman JE, Davis ME. Clinical experiences with systemically administered siRNA-based therapeutics in cancer. Nat Rev Drug Discov. 2015;14(12):843–856. - PubMed