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MolES Seminar: Gaurav Sahay (Oregon Health & Science University)
MolES Seminar: Gaurav Sahay (Oregon Health & Science University)
WhenTuesday, Mar 3, 2020, 1 – 2 p.m.
Campus locationMolecular Engineering (MOL)
Campus roomNanoES 181
Event typesLectures/Seminars
Event sponsorsMolecular Engineering and Sciences
Twitter#MolESseminar
Description

Molecular Engineering and Sciences Seminar Series
Abstract: Boosting Intracellular Delivery of mRNA therapeutics

Endosomal sequestration of lipid-based nanoparticles (LNPs) remains a formidable barrier to delivery. Structure-activity analysis of cholesterol analogues reveals that incorporation of C-24 alkyl phytosterols into LNPs (eLNPs) enhances gene transfection and the length of alkyl tail, flexibility of sterol ring and polarity due to -OH group is required to maintain high transfection. Cryo-TEM displays a polyhedral shape for eLNPs compared to spherical LNPs, while x-ray scattering shows little disparity in internal structure. eLNPs exhibit higher cellular uptake and retention, potentially leading to a steady release from the endosomes over time. 3D single-particle tracking shows enhanced intracellular diffusivity of eLNPs relative to LNPs, suggesting eLNP traffic to productive pathways for escape. Our findings show the importance of cholesterol in subcellular transport of LNPs carrying mRNA and emphasize the need for greater insights into surface composition and structural properties of nanoparticles, and their subcellular interactions which enable designs to improve endosomal escape. I will further discuss the application of eLNPs based mRNA therapeutics for the treatment of cystic fibrosis and inherited retinal degeneration.
 
This weekly seminar brings together students, faculty and invited guests from various disciplines across campus to explore current trends in molecular engineering and nanotechnology. It is a forum for active interdisciplinary discussions. These talks are open to the public and attract a diverse audience of students and faculty.

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