Mentors: Victoria Goldenshtein, Michael Tadross, Ph.D.
Department of Neurobiology
DART is a novel drug delivery system based on covalent interaction between the HaloTag ligand and the HaloTag receptor that acts as a homing device to enable the delivery of pharmaceutics to specific cell types. Currently, DART can only deliver one drug to one cell type at a time, we are trying to develop an orthogonal DART system for multiplex drug delivery. To achieve this we will use GRIP, a protein display system, and principles of directed mutagenesis to create a library with a large number of protein variants and subject them to selective binding pressure. Next-Generation Sequencing is used to identify the top DNA sequences. To measure the level of binding, cells were plated with a HaloTag vector and a fluorescent dye, and the resulting signal was quantified. Next, we will measure the binding affinity of the top sequences and the cross-reactivity with the original system in neurons. If successful, the dart system would offer potential a deeper understanding of the brain circuits.