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The Washington Research Foundation Fellowship

Jen Choi, Bioengineering

Jen Choi Jen Choi is currently a senior in the Department of Bioengineering. Though pre-med focused, her motivation to study bioengineering and become involved in research was rooted in her interest in the development of new therapies and diagnostics for medical applications. Her dream is to develop these therapies and someday use them in patients. She began her research experience the summer before her freshman year in Miqin Zhang’s lab. In the Zhang group, she worked on superparamagnetic iron oxide nanoparticles for delivery of therapeutics to the central nervous system. After 1.5 years, she switched to Suzie Pun’s lab, where she is now working on her capstone project. In this project, she is developing multi-functional polymers for targeted delivery of genetic material to the central nervous system. Previously, she has also participated in the Amgen Scholars Program at UCSD where she helped make vaccines against drugs of abuse. Jen plans to pursue an MD/PhD. Outside of lab, she enjoys running, baking, and long walks on the beach.

Mentor: Suzie Pun, Bioengineering

Project Title: Guanidinylation and Tet1 Targeting Peptide Modification of Cationic Copolymers for Gene Delivery

Abstract: As our understanding of the genetic basis for the pathophysiology of many diseases has broadened, gene therapy, which is the delivery of genetic material into cells in order to supplement or alter defective genes, is being explored as a potential treatment option. Despite its promise, no gene therapies have been approved for clinical use due to the lack of safe and effective vectors. There are many obstacles that must be overcome in order to produce safe and efficient vectors. First, the vector-DNA complex must navigate through the extracellular environment and be uptaken into the target cell. Then, the genetic material must achieve endosomal escape, be released from the complex, and then translocate into the nucleus where it can be transcribed and translated into functional or therapeutic proteins. In the Pun Lab, we previously synthesized a block-statistical copolymer comprised of different hydrophilic and hydrophobic segments aimed at providing a plethora of functionalities to the formed polyplexes. Due to this polymer’s unique architecture, it exhibits transfection efficiencies higher than branched polyethyleneimine, the gold standard for nonviral gene delivery, but still fails to reach the same level of transfection efficiency as seen with viral vectors. In this project, two additional modifications will be made to the copolymer and a library of well-defined polyplexes with varying formulations and structures will be synthesized and evaluated in vitro and in vivo. These modifications, guanidinylation and conjugation of a targeting peptide, aim to increase uptake into cells through electrostatic interactions and increase localization to the target cell type. From these studies, the ideal method to incorporate both modifications into one system to improve transfection efficiency and the structure-function effects on transfection efficiency will be evaluated.