Ionizable Lipids with Optimized Linkers Enable Lung-Specific, Lipid Nanoparticle-Mediated mRNA Delivery for Treatment of Metastatic Lung Tumors

Lipid nanoparticles (LNPs) have emerged as a groundbreaking delivery system for vaccines and therapeutic mRNAs. Ionizable lipids are the most pivotal component of LNPs due to their ability to electrostatically interact with mRNA, allowing its encapsulation while concurrently enabling its endosomal escape following cellular internalization. Thus, extensive research has been performed to optimize the ionizable lipid structure and to develop formulations that are well tolerated and allow efficient targeting of different organs that result in a high and sustained mRNA expression. However, one facet of the ionizable lipids’ structure has been mostly overlooked: the linker segment between the ionizable headgroup and…

• IS
  Israel Science Foundation

  Award: 2012/20
• HE
  H2020 European Research Council

  Award: 101055029
• HH
  H2020 Health

  Award: 825828