Uveal melanoma is rare, but it is the most common eye cancer, and often a terminal disease due to the high hepatic metastatic potential. There are currently no available effective therapeutic options targeting uveal melanoma directly and no adjuvant therapies that have shown significant survival benefits in patients. The high frequency of the diagnosed patient cases that have the tumorigenic prominent mutation of Q209 in the heterotrimeric G protein alpha subunit Gαq and Gα11 (46% and 44%, respectively and mutually exclusive) leads to a constantly active proliferation signaling pathway via activation of various downstream effectors such as MAPK and YAP pathways. We developed an intracellular trap highly specifically against the active form of GNAQ and GNA11 using directed molecular evolution and are using lipid nanoplatforms for targeted delivery of the in vitro transcribed mRNA therapeutic trap gene to disrupt major pathogenic pathways in uveal melanoma. The results from this work could have significant implications in the development of new therapeutic strategies for uveal melanoma.

Therapeutic gene delivery approach to targeting constitutively active pathways in uveal melanoma

256th National Meeting (2018)

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