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Targeted and Local siRNA Drug Delivery

Primary Investigator:
Craig Duvall

Brief Description of Project:
Our lab has recently synthesized and screened a new library of synthetic polymers designed to form nanoparticles for delivery of short interfering RNA (siRNA) for gene therapy (targeted gene silencing) applications. We have optimized the pH-responsiveness of these polymeric carriers to enable endosomal escape and intracellular delivery / gene silencing bioactivity of siRNA. We are now seeking to further improve upon this promising nanocarrier for biomedical applications.

We are seeking researchers to contribute to two aspects of this project:

  1. Incorporation of targeting ligands to improve cell- and tissue-specific action in order to improve drug potency and reduce off-target effects following intravenous siRNA nanocarrier delivery.
  2. Build upon technologies invented in our laboratory for temporally-controlled, local delivery of siRNA nanocarriers in order to achieve sustained, potent bioactivity without the requirement for multiple applications / doses.

Candidate Qualification:
Highly motivated students interested in research who have taken general chemistry and preferably BME 103 (biomaterials). Completion of organic chemistry class and lab are also desired but not required.

Nature of Supervision:
The undergraduate researcher will have the opportunity to meet at least weekly to discuss research progress with the PI. Hands-on training and support will be provided by a graduate student who will serve as a mentor.

A Brief Research Plan (period is for 10 weeks):
Students will be involved in synthesis and in vitro testing of new forms of this nanocarrier amenable to functionalization with targeting ligands and / or fabrication of biodegradable polymer-based depots for sustained, local nanocarrier delivery. This will require polymer synthesis, basic nanoparticle characterization by GPC, DLS, TEM, and 1H-NMR, measurement of intracellular delivery in vitro, and measurement of gene expression. The student will be encouraged to interface and collaborate with other members of the Duvall lab and to utilize VINSE facilities.

Number of Open Slots: 2

Contact information:
Craig L. Duvall, Ph.D.
Assistant Professor
Vanderbilt University
Department of Biomedical Engineering
PMB 351631
2301 Vanderbilt Place
Nashville, TN 37235-1631
email: craig.duvall@vanderbilt.edu
office phone: (615)322-3598
fax: (615)343-7919
web:  http://research.vuse.vanderbilt.edu/biomaterials/Duvall/index.html