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

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.

Next-generation materials for RNA–lipid nanoparticles: lyophilization and targeted transfection

“…In addition to specific peptides or aptamers, RNA-LNPs can be passively delivered into specific tissues or organs by the selection of specific lipids for use in the LNPs. 69,73,75,92–95 LNPs containing the ionizable lipid C12-200 (1,10-[[2-[4-[2-[[2-[bis(2-hydroxydodecyl)amino]ethyl](2-hydroxydodecyl)amino]ethyl]-1-piperazinyl]ethyl]imino]bis-2-dodecanol) exhibit improved specific delivery of LNPs into muscles. 73,94,95 Ma et al prepared neurotransmitter-derived lipidoids (NT-lipidoids), which can cross the BBB and deliver antisense oligonucleotides (ASOs) against tau when administered by intravenous injection.…”

“…73,94,95 Ma et al prepared neurotransmitter-derived lipidoids (NT-lipidoids), which can cross the BBB and deliver antisense oligonucleotides (ASOs) against tau when administered by intravenous injection. 73,93…”

The interplay between cardiac dyads and mitochondria regulated the calcium handling in cardiomyocytes

“…Besides the AAV vector-based gene therapy, several non-viral vectors or strategies had been applied for inherit cardiovascular diseases. Nanoparticles had been introduced to gene therapy for several years, as it presented advantages in effective compositions, especially for lipid nanoparticles (LNP) (Godbout and Tremblay, 2022). Experiments proved LNPs could be delivery RNAs to brain, lungs, heart, liver and bones.…”

Biodrug Delivery Systems: Do mRNA Lipid Nanoparticles Come of Age?

“…Modifying the composition of the lipids in LNPs allows for the more specific delivery of the LNPs to some organs (Figure 1). This topic has been extensively dealt with elsewhere [6].…”

“…Modifying the composition of the lipids in LNPs allows for the more specific delivery of the LNPs to some organs (Figure 1). This topic has been extensively dealt with elsewhere [6]. Fusion merges the lipids of the nanoparticle with the ones in the cell membrane, ultimately releasing the contents of the nanoparticles inside the cell.…”