Lipid Nanoparticles for Cell-Specific <i>in Vivo</i> Targeted Delivery of Nucleic Acids

Abstract

The last few years have witnessed a great advance in the development of nonviral systems for in vivo targeted delivery of nucleic acids. Lipid nanoparticles (LNPs) are the most promising carriers for producing clinically approved products in the future. Compared with other systems used for nonviral gene delivery, LNPs provide several advantages including higher stability, low toxicity, and greater efficiency. Additionally, systems based on LNPs can be modified with ligands and devices for controlled biodistribution and internalization into specific cells. Efforts are ongoing to improve the efficiency of lipid-based gene vectors. These efforts depend on the appropriate design of nanocarriers as well as the development of new lipids with improved gene delivery ability. Several ionizable lipids have recently been developed and have shown dramatically improved efficiency. However, enhancing the ability of nanocarriers to target specific cells in the body remains the most difficult challenge. Systemically administered LNPs can access organs in which the capillaries are characterized by the presence of fenestrations, such as the liver and spleen. The liver has received the most attention to date, although targeted delivery to the spleen has recently emerged as a promising tool for modulating the immune system. In this review, we discuss recent advances in the use of LNPs for cellspecific targeted delivery of nucleic acids. We focus mainly on targeting liver hepatocytes and spleen immune cells as excellent targets for gene therapy. We also discuss the potential of endothelial cells as an alternate approach for targeting organs with a continuous endothelium.

Materials promoting viral gene delivery

“…397 Recent reviews on non-viral application of lipids for gene delivery can be found elsewhere. 398,399 Lipids for viral gene delivery, which are discussed in the following section are summarized in Table 5.…”

Nanocarrier-Based Drug Delivery for Melanoma Therapeutics

“…They also demonstrated that lipids with cyclic amino head groups activate the MYD88/RLR independent intracellular stimulator of interferon genes (STING) pathway. In addition, cyclic lipids that can activate STING are condensed with mRNA to prepare lipid nanoparticles [131]. Therefore, nanoparticle-mediated endocytosis improves the cell internalization, thereby activating the intracellular STING pathway.…”

Epigenetic editing: Dissecting chromatin function in context

“…While not yet broadly applicable, nanoparticles potentially offer a wide range of applications including efficient and site-specific delivery of a CRISPR/Cas9 cargo in vivo. [162][163][164] They possess a high loading capacity and good stability, as well as the potential for timely control of their cargo release. The current focus is on the conjugation of different nanomaterials to improve their safety, cellular intake and specificity towards a designated cell type or tissue.…”

“…[166,167] One of the major challenges of delivering an epigenome editing system in vivo is to ensure that the cargo won't hit the germline -thus avoiding the ethical issue of transmitting the biological changes to the offspring -and to minimize the effects of epigenome therapy in nonrelevant tissues. Some nanocarriers target specifically the liver and spleen, [163] and ex vivo epigenome editing can also be considered as a reliable technique with minimum off-target effects, although its application is limited to a few cell types. [168] AAV can be further engineered to direct their tropism to the cell type of interest through a ligandreceptor interaction.…”