This presentation will address on the major achievements and future perspectives of delivery systems for oligonucleotide and mRNA therapeutics based on the nanostructures constructed through a self-assembly of polypeptide-based block copolymers. Particularly, the focus will be given to systemic delivery of oligonucleotides (siRNA and ASO) crossing blood-brain barrier (BBB) for the treatment of intractable brain diseases, including glioblastoma and neurodegenerative disorders, by the self-assembly system of block ionomers. The presentation includes the brief insight into the two-step mechanism of block catiomer assembly in aqueous milieu with oligonucleotides,<i>i.e.</i>primary assembly of unit polyion complex (uPIC) from minimal catiomer/oligonucleotides pair for charge-neutralization followed by the secondary association of uPIC to generate multimolecular micelles (PIC micelles). Then, a few examples will be shown to appeal the efficacy of uPIC and PIC micellar formulations in glioblastoma treatment by oligonucleotide therapeutics. Regarding the application of PIC micelles for neurodegenerative diseases, I would like to discuss the new paradigm for crossing the BBB, <i>i.e.</i>glucosylated PIC micelles targeting glucose transporter 1 (GLUT1) overexpressing on the luminal side of brain capillary endothelial cells. If time allows, the feasibility of mRNA therapeutics will also be addressed because issues of stability and immunogenicity of mRNA were dramatically improved by the use of PIC micelles as delivery systems.

Poly(ethylene glycol)-polypeptide block copolymers for delivering nucleic acid-based therapeutics into brain

2019 Fall National Meeting

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.