Responsive delivery of therapeutic proteins

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The proposed research will develop micelles formed via liquid-liquid phase separation for therapeutic protein delivery. This project will focus on the co-delivery of Cas9 and guide RNA for gene editing applications. The micelles will be formed through electrostatic interactions between net negatively charged protein-RNA particles and net positively charged polymers. This liquid-liquid phase separation will stabilize proteins in a highly ionic, hydrated environment during storage, but will deliver the therapeutic cargo upon cellular internalization. Formation of micelles between anionic proteins and cationic-neutral block copolymers will be studied by dynamic light scattering (DLS). Polymer composition and molecular weight will be screened to identify protein/polymer combinations that promote robust micelle formation under physiological conditions. The ability of the micelles to release the protein cargo will be evaluated as a function of solution pH and ionic strength. However, to efficiently deliver the proteins intracellularly additional methods for responsive release may be needed. We will also investigate the use of photoresponsive copolymers to mediate light driven therapeutic release.

Lab: Obermeyer Research Group

Direct Supervisor: Justin Horn (and Allie Obermeyer)

Position Dates: 5/28/2019 - 9/13/2019

Hours per Week: 40

Paid Position: Yes

Credit: Yes 

Qualifications: molecular biology, polymer synthesis, protein production

Eligibility: Sophomore, Junior, Senior; SEAS only

Alissa Park (ap2622@columbia.edu)