Rondine Allen

Mentor: Kevin G. Rice, PhD

Year Entered Into Program: 2013

Terminal Degree(s) Received and Year: PhD 2018

Affiliations

Medicinal and Natural Products Chemistry

Research Description

The field of gene therapy involves the use of nucleic acids to treat or prevent a genetic disease by introducing, inactivating or replacing a mutated gene. This approach differs from traditional drug therapy, in that it aims to correct deficient genes instead of treating a symptom. The therapeutic gene is delivered to the affected cells using a gene delivery vector. Once in the target cell, the DNA is then transcribed and translated producing a protein, which can compensate for the activity of the mutated gene. There are many barriers preventing the successful use of gene therapy therapeutically. The most challenging aspect is the method of delivery. Upon dosing an unprotected nucleic acid in vivo, it is rapidly recognized and degraded by degradative enzymes. Therefore, a vector is needed to provide protection to the enclosed nucleic acid. The Rice lab focuses on the development of non-viral gene delivery systems. Over many years, the lab has developed synthetic peptides that bind to DNA and stabilize it from degradation in the blood. Gene formulations developed in our lab are tested in mice to determine their pharmacokinetic and biodistribution profiles. These studies have revealed, that almost all gene delivery systems are rapidly captured by the liver. More specifically, they are endocytosed by scavenger receptors of Kupffer cells of the reticuloendothelial system (RES) of the liver. This results in degradation of the DNA. My research project focuses on the development of scavenger receptor inhibitors to block the uptake of the DNA formulations by the RES, in order to achieve targeted gene delivery. 

Awards

  • Sloan Mini Grant Travel Award
  • Advancing Science Travel Award
  • Fellowship appointment on the Pharmacological Sciences Training Program (NIH T32 GM067795), University of Iowa 2015-2016
  • Institutional Fellowship support on the Pharmacological Sciences Training Program (NIH T32 GM067795), University of Iowa, 2014-2015

Publications

  1. Baumhover NJ, Duskey JT, Khargharia S, White CW, Crowley ST, Allen RJ and Rice KG.:  Structure-Activity Relationship of PEGylated Polylysine Peptides as Scavenger Receptor Inhibitors for Non-Viral Gene Delivery., Molecular Pharmaceutics, 12:4321-8, 2015.  PMCID: PMC4837691

Research