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SCSB Lunch Series: Human Paraneoplastic antigen Ma2 (PNMA2) forms icosahedral capsids that can be engineered for mRNA delivery
February 23 | 12:00 pm - 1:00 pm
Date: Friday, February 23, 2024
Time: 12:00pm – 1:00pm
Location: Simons Center Conference room 46-6011 + Zoom Meeting (https://mit.zoom.us/j/93707327771)
Speaker: Yugang Zhang, Ph.D.
Affiliation: Simons Fellow, Feng Zhang Laboratory, McGovern Institute for Brain Research, MIT
Talk title: Human Paraneoplastic antigen Ma2 (PNMA2) forms icosahedral capsids that can be engineered for mRNA delivery
Abstract: To build a protein-based delivery vehicle, we systematically investigate human PNMA proteins and find that a number of PNMAs are secreted by human cells and form capsid in vitro. We determine that PNMA2 forms icosahedral capsids efficiently but does not naturally encapsidate nucleic acids. We resolve the cryo-electron microscopy (cryo-EM) structure of PNMA2 and leverage the structure to design engineered PNMA2 (ePNMA2) particles with RNA packaging abilities. Recombinantly purified ePNMA2 proteins package mRNA molecules into icosahedral capsids and can function as delivery vehicles in mammalian cell lines, demonstrating the potential for engineered endogenous capsids as a nucleic acid therapy delivery modality.