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Publication : Nucleoside-modified VEGFC mRNA induces organ-specific lymphatic growth and reverses experimental lymphedema.

First Author  Szőke D Year  2021
Journal  Nat Commun Volume  12
Issue  1 Pages  3460
PubMed ID  34103491 Mgi Jnum  J:349551
Mgi Id  MGI:6725396 Doi  10.1038/s41467-021-23546-6
Citation  Szoke D, et al. (2021) Nucleoside-modified VEGFC mRNA induces organ-specific lymphatic growth and reverses experimental lymphedema. Nat Commun 12(1):3460
abstractText  Lack or dysfunction of the lymphatics leads to secondary lymphedema formation that seriously reduces the function of the affected organs and results in degradation of quality of life. Currently, there is no definitive treatment option for lymphedema. Here, we utilized nucleoside-modified mRNA encapsulated in lipid nanoparticles (LNPs) encoding murine Vascular Endothelial Growth Factor C (VEGFC) to stimulate lymphatic growth and function and reduce experimental lymphedema in mouse models. We demonstrated that administration of a single low-dose of VEGFC mRNA-LNPs induced durable, organ-specific lymphatic growth and formation of a functional lymphatic network. Importantly, VEGFC mRNA-LNP treatment reversed experimental lymphedema by restoring lymphatic function without inducing any obvious adverse events. Collectively, we present a novel application of the nucleoside-modified mRNA-LNP platform, describe a model for identifying the organ-specific physiological and pathophysiological roles of the lymphatics, and propose an efficient and safe treatment option that may serve as a novel therapeutic tool to reduce lymphedema.
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