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Review
. 2022 Oct 7;14(10):2129.
doi: 10.3390/pharmaceutics14102129.

Delivery of RNAs to Specific Organs by Lipid Nanoparticles for Gene Therapy

Kelly Godbout  1   2 , Jacques P Tremblay  1   2
Affiliations
Review

Delivery of RNAs to Specific Organs by Lipid Nanoparticles for Gene Therapy

Kelly Godbout et al. Pharmaceutics. .

Abstract

Gene therapy holds great promise in the treatment of genetic diseases. It is now possible to make DNA modifications using the CRISPR system. However, a major problem remains: the delivery of these CRISPR-derived technologies to specific organs. Lipid nanoparticles (LNPs) have emerged as a very promising delivery method. However, when delivering LNPs intravenously, most of the cargo is trapped by the liver. Alternatively, injecting them directly into organs, such as the brain, requires more invasive procedures. Therefore, developing more specific LNPs is crucial for their future clinical use. Modifying the composition of the lipids in the LNPs allows more specific deliveries of the LNPs to some organs. In this review, we have identified the most effective compositions and proportions of lipids for LNPs to target specific organs, such as the brain, lungs, muscles, heart, liver, spleen, and bones.

Keywords: CRISPR/Cas9 delivery; gene therapy; lipid nanoparticles; mRNA delivery; specific organ delivery.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Key components of lipid nanoparticles (LNPs). LNPs are mainly composed of ionizable cationic lipids, helper lipids, cholesterol, and polyethylene glycol (PEG) lipids. Image created with BioRender.com.
Figure 2
Figure 2
Chemical structures of some lipids used in LNPs. LNPs are generally composed of four categories of lipids: ionizable cationic lipids, helper lipids (phospholipids), cholesterol, and PEG lipids. A permanently charged cationic lipid can sometimes be added. TCL053, C12-200, YSK05, 5A2-SC8, DLin-K2-DMA, 9A1P9, DLin-MC3-DMA, and 306-O12B-3 are the principal ionizable cationic lipids used. DPPC, DOPE, and DSPC are the main helper lipids used. DMG-PEG and DSPE-PEG are the most used PEG lipids. There are three kinds of permanently charged cationic lipids that are mainly used: DOTAP, DOTMA, and 18PA. Image created with BioRender.com. The figure was adapted from [38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54].
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