Intravitreal delivery of LATS1 mRNA by lipid nanoparticles as an effective strategy for uveal melanoma therapy - PubMed
5 days ago
- #mRNA Therapy
- #Lipid Nanoparticles
- #Uveal Melanoma
- Uveal melanoma (UM) is a rare and aggressive intraocular malignancy driven by persistent activation of Yes-associated protein (YAP) due to loss of Hippo kinases like LATS1.
- Restoring LATS1 activity via mRNA therapy is a promising strategy to suppress YAP and treat UM.
- Lentivirus-mediated LATS1 overexpression and in vitro transcribed LATS1 mRNA inhibited UM cell proliferation.
- Two lipid nanoparticle (LNP) formulations (SM102 and MC3) were compared for intraocular mRNA delivery, with SM102-LNPs showing superior translation efficiency.
- Intravitreal administration of LATS1 mRNA-loaded SM102-LNPs significantly suppressed tumor growth in an orthotopic UM mouse model.
- The delivered mRNA was predominantly detected in tumor cells, with some expression in Müller glial cells.