Student(s): Kavya Famolari
Project: Investigating the Effects of Polypeptide Length and Salt Concentration on Complexation of Nucleic Acids
Advisor(s): Whitney Blocher McTigue
Abstract
Nucleic acid-based therapies, including vaccines and gene therapies, are limited by their reliance on cold chain infrastructure, thus creating challenges to global access. Electrostatic complexation between polypeptides and nucleic acids offers a strategy for stabilizing fragile cargo. These complexes arise from the attractions between oppositely charged nucleic acid phosphate groups and poly-L-lysine amine groups. Their stability is governed by parameters within their aqueous environments that dictate whether resulting complexes form coacervate droplets or solid precipitates. In this study, we investigate how poly-L-lysine chain length and nucleic acid size and structure affect the stability and morphology of complexes. Poly-L-lysine chains of five lengths were combined with three nucleic acids: dsDNA, sheared dsDNA fragments, and baker’s yeast tRNA. The resulting complexes were analyzed through turbidity, microscopy, and salt resistance studies. Turbidity measurements revealed that all systems peak complexation near a 0.5 charge fraction, but longer PLK chains resulted in high turbidity readings across a wider range of charge fractions. Salt resistance studies showed that complexes with longer PLK chains and nucleic acids persisted at higher salt concentrations, reflecting stronger polymer-polymer interactions. Our results highlight how polyelectrolyte length and structure together determine phase behavior and salt resilience, ultimately informing the design of therapeutic drug delivery systems as a step toward relieving the dependence on the cold supply chain.
About Kavya Famolari
Major: IDEAS
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