Dimeric IgA targets intracellular oncogenes; plus taRNAs and more

A group led by Jose Conejo-Garcia at H. Lee Moffitt Cancer Center and Research Institute showed in Immunity that dimeric IgA can enter tumor cells through transcytosis, target mutated cytoplasmic oncogenes and expel them from the cell. KRAS^G12D-specific dimeric IgA limited the growth of KRAS^G12D-mutated ovarian and lung cancers in mice more effectively than the small molecule KRAS^G12D inhibitor MRTX1133 from  Mirati Therapeutics Inc. (NASDAQ:MRTX).

Researchers at the  University of Chicago and collaborators including  Tornado Bio Inc. co-founder Bryan Dickinson reported in Nature Communications bifunctional constructs that bind to a target mRNA and upregulate its translation. The constructs, dubbed “translation-activating RNAs” (taRNAs), comprise a guide RNA and a translation machinery-recruiting internal ribosome entry site (IRES). The authors used taRNAs to amplify SYNGAP1 expression in patient-derived cells and showed successful delivery of the taRNAs to cell lines, primary neurons and mouse liver in vivo using nanoparticles...