Internal Oligoguanidinium-based Cellular Transporter Enhances Antisense Efficacy of Morpholinos in in vitro and Zebrafish model

Efficient cellular transporter is highly desirable for the therapeutic applications of antisense phosphorodiamidate morpholino oligonucleotides (PMOs) as Vivo-PMO and PPMO have limitations for in-vivo study. We report here a novel internally tetraguanidinium linked nonpeptidic cellular transporter having conformationally rigid backbone composed of pharmacologically compatible heterocyclic six-membered rings which internalizes efficiently into cells in full growth medium and ubiquitously distributed into zebrafish embryos. It efficiently transports antisense PMO in-vitro and in-vivo zebrafish embryos. Comparative study with Gene Tools Vivo-PMO revealed that our cellular-transporter conjugated PMO shows better antisense efficacy.