Definition

A lipid nanoparticle (LNP)-based formulation consisting of a biscistronic mRNA that encodes two independent epigenomic controllers targeting the proto-oncogene MYC (c-Myc), with potential antineoplastic activity. Upon administration of LNP encapsulated MYC-targeting mRNA-based agent OTX-2002, the lipid formulation promotes the uptake by tumor cells. The biscistronic mRNA is then translated by the cellular protein translation machinery to produce two independent epigenomic controllers consisting of a DNA binding domain and an epigenetic effector protein. The two epigenomic controllers bind to regulatory regions on the MYC insulated genomic domain (IGD), a DNA loop bound by CTCF (CCCTC-binding factor). This downregulates MYC expression pre-transcriptionally, which may inhibit proliferation in susceptible tumor cells. MYC, a proto-oncogene overexpressed in a variety of cancers, plays a role in the regulation of transcription and cell proliferation.