Research
As a Molecular Pathogenesis and Therapeutics (MPT) doctoral candidate at the University of Missouri (MU) I explore the interactions between RNA and protein that drive RNA packaging into extracellular vesicles (evRNA). Under the guidance of Dr. Donald Burke and with the help of a highly motived and supportive lab, my team of undergrads and I look to identify and appropriate native packaging mechanisms for the delivery of RNA therapeutics (aptamers, ribozymes, miRNA, etc.). While attempting to identify native conserved mechanisms we also evolve novel molecules that can package under diverse conditions through the process of SELEX. As a lab we utilize high-throughput sequencing and an in-house developed bioinformatics pipeline (FASTAptamer) to parse through millions of sequence reads and identify enrichment among divergent trajectories.
Small non-coding nucleotide transcripts occupy the greater portion of my graduate research and as a Biomolecular Engineer I am receiving training in manipulating these transcripts for research and translational routes. My dissertation work focuses primarily on developing the RNA aptamers pioneered by Dr. Donald Burke and Dr. Larry Gold into a novel gene therapy. Utilizing broadly inhibitory anti-HIV-RT aptamers which target highly conserved protein residues I am developing a combinatorial platform for anti-HIV RNA therapeutics. Alternatively, using the aptamers as a targeting mechanism to drive RNA packaging into the budding virus, we are expanding the functionality of our system by co-transcribing secondary inhibitory mechanisms into our transcripts (RNAi, mRNA, aptamers, etc.). We are currently developing a novel selection mechanism to separate RNA transcripts demonstrating increased packaging potential to explore the native packaging mechanisms employed by the virus for genome and accessory RNA incorporation. Expanding on this system I am implementing a second trajectory for the lab to look at the functionality of extracellular vesicle RNA (EVs, Exosomes, etc.) packaging in a more translational therapeutic capacity. Others in the lab are looking at the evolution of RNA in an origins of life light while attempting to identify functional RNA structures that are capable of performing complex intracellular functions akin to protein enzyme (ribozymes). Others still are evaluating promoter strength and self-targeting of lentiviral vectors as we move our RNA aptamers into a humanized mouse model for HIV inhibition studies.
After completing my Bachelors in Biology (with an emphasis in virology) at UC Irvine I worked for a number of years in industry screening blood samples for the presence of viral contaminates (HIV, HAV, HBV, HCV, WNV, etc.) with a diagnostics group called National Genetics Institute (NGI) based out of Los Angeles, CA. The experience I gained there gave me the insight and drive to continue my education so that I could develop a biotechnology of my own into a small pharma company. I have just completed a complementary certificate program in Life Sciences Innovations through the University of Missouri which has trained me in some of the finer regulatory and intellectual property details of developing a biotech startup. Following my dissertation I hope to find a post-doc position in a lab with close ties to industry so that I can work together with a team to develop translational research to bring hard sought science out of the lab and into the market.
- Kyle J. Hill
