ChBE Seminar Series: You-Yeon Won

Tuesday, April 22, 2008
11:00 a.m.-12:00 p.m.
Room 2110 Chemical & Nuclear Engineering Bldg.
Professor Kyu Yong Choi
(301) 405-1907
choi@eng.umd.edu

Triblock Copolymer Micelle-Based DNA/siRNA Delivery

Presented by You-Yeon Won
Purdue University School of Chemical Engineering
Forney Hall of Chemical Engineering

Safe and effective delivery of nucleotide-based therapeutics to the targeted cells remains one of the largest obstacles to the clinical realization of the concept of gene therapy. Polymers, particularly polycations, have become very popular components of non-viral carriers for DNA and siRNA because of their safety and the relative ease with which their chemical and physical properties can be engineered for specific applications. However, for in vivo applications the conventional polymer-based approaches (i.e., those based on simple polycations or PEGylated polycations) fall far short of being able to fulfill all the functions required for successful delivery of DNA or siRNA, with the largest limitation being the insufficient stability of the system under in vivo conditions. Recently, in an attempt to address this limitation, we developed a novel polymer-based DNA/siRNA delivery system. Our approach uses nanoparticles (“micelles”) formed by an ABC-type triblock copolymer (“terpolymer”) as structural building blocks for constructing stable, small-size DNA/siRNA complexes. Over traditional polymer chain-based approaches, this new polymer micelle-based design affords (i) particle size above limits for plasma renal clearance (> about 10 nm) but still below limits for cellular uptake (< a couple of hundred nanometers), and also (ii) large cargo space for ‘helper’ molecules (e.g., fluorescent dye molecules for intracellular tracking and quantum-dot nanoparticles for in vivo imaging). In this talk, I will discuss the results of our recent studies which demonstrate the (a) molecular-level structural characteristics, (b) stability against dissociation, enzymatic degradation and serum protein adsorption, (c) cytotoxicity, and (d) gene transfection/silencing efficiencies of this new polymer micelle-based gene delivery formulation. These properties of the micelleplex DNA/siRNA carriers will be discussed in comparison with those of conventional polyplex equivalents derived from simple polycations and PEGylated polycations.

Audience: Graduate  Faculty  Post-Docs 

 

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