Lipid nanoparticle-based mRNA candidates elicit potent T cell responses

Abstract

Addition of limited amounts of fusogenic lipid DOPE (Orange) and beta-sitosterol (red) improves transfection efficacy of dendritic cells and improves CDB* T-cell responses.

Lipid- and Polymer-Based Nanocarrier Platforms for Cancer Vaccine Delivery

“…54 Another study explored the role of the sterol component (cholesterol versus βsitosterol) as well as the fusogenic helper lipid in optimizing the transfection efficiency and T cell activation by mRNA LNPs. 55 The search for the optimal lipids for mRNA LNPs has been the subject of many investigations. Researchers recently synthesized more than 100 lipids to optimize mRNA stability and delivery and found that lipids with branched hydrophobic tails outperformed linear lipids.…”

“…An mRNA LNP formulation was designed to target APCs in the spleen by optimizing the lipid composition, specifically the type of helper lipid . Another study explored the role of the sterol component (cholesterol versus β-sitosterol) as well as the fusogenic helper lipid in optimizing the transfection efficiency and T cell activation by mRNA LNPs …”

Fusogenic Coiled-Coil Peptides Enhance Lipid Nanoparticle-Mediated mRNA Delivery upon Intramyocardial Administration

“…There are several biomaterial designs and modifications that show promise for the safe delivery of mRNA, including lipids, lipid-like materials, polymers, and inorganic nanoparticles . Currently, lipid nanoparticles (LNPs) are the state-of-the-art vector for packaging, protecting, and releasing mRNA molecules within cells, as evidenced by the success of two COVID-19 mRNA-LNP vaccine formulations that received FDA approval in 2020. − LNPs are typically composed of four lipid componentsan ionizable lipid, cholesterol, a helper lipid, and a poly­(ethylene glycol)-lipid conjugate, which can be varied to produce distinct formulations with desired physicochemical properties. − However, the efficacy of LNPs in transfecting cells is limited by their ability to induce endo/lysosomal escape since they enter cells through endocytosis and are subjected to endolysosomal trafficking . Typically, less than 5% of the intracellularly delivered dose of mRNA by LNPs is able to reach the cytoplasm .…”

Efficient mRNA delivery using lipid nanoparticles modified with fusogenic coiled-coil peptides

“…2 Currently, the most advanced nonviral nucleic acid delivery system is lipid nanoparticles (LNPs). [14][15][16] LNPs are composed of an ionizable lipid to condense the genetic cargo and release it after entering the cells; a cholesterol moiety to stabilize the LNP structure; a helper lipid; and a PEGylated lipid to improve colloidal stability and reduce protein absorption. 17 The first siRNA drug, named Onpattro (Patisiran), was approved in 2018 by the FDA and was designed to treat polyneuropathies induced by hereditary transthyretin-mediated amyloidosis (hATTR) in adults.…”