CMCB Life Sciences Seminar: Prof. Ali Miserez, Nanyang Technology University Singapore

Host: Nicole Poulsen (B CUBE)

Title: "Phase-Separating Peptide Coacervates as Universal Carriers for Intracellular Delivery of Macromolecular Therapeutics"

Abstract:

Macromolecular therapeutics (peptides, proteins, mRNAs, plasmid DNAs, etc…) hold vast therapeutic potential across human disease states by providing opportunities to address targets that have proven refractory to traditional approaches; however, a critical impediment for the successful application of these modalities is their inability to cross cellular membranes, preventing access to intracellular targets. Current approaches to solve this key issue are based on nanoscale carriers to deliver the payloads, which however have several drawbacks including a tendency to get entrapped in endosomal compartments, poor biodistribution, and in some cases dose-limiting toxicity.

In this talk, I will present a unifying delivery strategy of macromolecular therapeutics recently developed by our team that is cargo-agnostic, does not cross the cell membrane through classic endocytosis, and non-cytotoxic¹. This new method exploits Liquid-Liquid Phase Separation (LLPS) of engineered peptides self-assembling into therapeutic-carrying coacervate microdroplets² that are capable to release their cargo in the cytosol. Overall, this platform represents a general and robust strategy for the intracellular delivery of a range of macromolecular modalities with promising potential for the treatment of a spectrum of human diseases such as cancers, metabolic diseases, or genetic disorders.

Everybody is very welcome.