| Description |
Title: “Engineering Synthetic Self-Amplifying RNA Circuits for Therapeutic Applications”
Committee:
Ron Weiss, MIT
Douglas Densmore, BU ECE (Advisor, Chair)
Xue Han, BU BME
Ahmad Khalil, BU BME
Abstract:
Self-amplifying RNA replicons are an attractive alternative to traditional nucleic acid based therapies, providing high, sustained expression compared to non-replicating RNA without the risk of genomic integration associated with viral vectors. Replicons are derived from a viral genome, but utilize the viral replication machinery to produce heterologous genes rather than the structural proteins required to produce virions. Despite being used for a variety of therapeutic applications, ranging from vaccination to genetic reprogramming, regulating expression from replicons remains relatively unexplored. In this study, we take a synthetic biology approach toward engineering a Venezuelan Equine Encephalitis (VEE) replicon, resulting in the dynamic control of multiple genes expressed from a single replicon in response to a small molecule input.
Synthetic biology aims to create and characterize libraries of highly predictable and modular genetic parts that can be compiled to produce complex genetic circuits. To this end, we have generated a collection of parts that can modulate replicon translation, explored various replicon-based expression platforms, and designed small molecule inducible replicon circuits. Using these circuits, we will pursue two therapeutically relevant applications: a pulsing circuit for transient expression of a protein involved in muscular dystrophy amelioration and a “one-shot” prime/boost circuit for Respiratory Syncytial Virus (RSV) vaccination. |
