Chemical & Biomolecular Engineering Department of Chemical and Biomolecular Engineering University of Illinois University of Illinois at Urbana - Champaign
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Daniel W. Pack

Daniel W. Pack
Pack Group Web Site

Contact Information:
e-mail:
phone: (217) 244-2816
fax: (217) 333-5052

114 Roger Adams Lab
MC-712, Box C-3
600 S. Mathews Ave.
Urbana, IL 61801

Associate Professor
B.S., University of Illinois, Urbana-Champaign, 1990
Ph.D., California Institute of Technology, 1997
Postdoctorate, Massachusetts Institute of Technology, 1997-1998

ENGINEERING OF ADVANCED DRUG DELIVERY SYSTEMS

Human gene therapy - the use of genetic material for the prevention, control or treatment of disease - shows great promise for treating medical conditions ranging from muscular dystrophy to cancer to AIDS. However, the lack of safe and efficient DNA-delivery methods is one of the most imposing obstacles to in vivo gene therapy. The goal of our research is to apply an engineering design approach to create improved materials for construction of gene delivery vehicles. Two examples of our approach are described below.

Directed evolution of viruses:

Viruses have evolved to be very efficient DNA-delivery vehicles, and therefore are attractive candidates for gene therapy. Unfortunately, the environments in which the viruses have evolved are dissimilar to those which are encountered in gene therapy applications. For instance, recombinant retroviruses are currently the most commonly used virus for gene therapy, but retroviruses are highly labile making them notoriously difficult to purify and concentrate. In addition, viruses have evolved a natural host-cell preference which very often is different from that required for a particular application.

To produce viruses optimized for gene therapy, it will be necessary to engineer the desired properties (e.g., stability or cell specificity) into the virus structure while retaining viral infectivity. To achieve this goal we are employing directed molecular evolution to modify the viral surface proteins. Thus, we create a large library of random mutant viruses, each displaying a unique surface protein, and apply an external "selection pressure" such as infectivity on a new cell type. The power of this method lies in the fact that we can "evolve" viruses toward a desired property with little insight on the virus structure a priori.

Design and synthesis of "artifical viruses":

Non-viral gene delivery vehicles based on polymers or lipids are safer and easier to produce than viruses, but are currently much less efficient. Delivery of DNA by these materials can be broken down into potential limiting steps such as targeting to the cell surface, internalization, transport into the cytoplasm and transport to the nucleus. By developing quantitative assays (e.g., based on flow cytometry) for each of these key steps, we are elucidating the structure-function relationship of various gene delivery vehicles. This increased understanding of the process of gene delivery is allowing us to design and synthesize new materials with which we may construct "artificial viruses."

Selected Publications

H.N. Vu, J.D. Ramsey and D.W. Pack, "Engineering of a stable retroviral gene delivery vector by directed evolution," Molecular Therapy: The Journal of the American Society of Gene Therapy, 16, 308-314 (2008).

H. Hosseinkhani, M. Hosseinkhani, N.P. Gabrielson, D.W. Pack, A. Khademhosseini and H. Kobayashi, "DNA nanoparticles encapsulated in 3D tissue-engineered scaffolds enhance osteogenic differentiation of mesenchymal stem cells," Journal of Biomedical Materials Research Part A, 85A, 47-60 (2008).

S.C. Wuang, K.G. Neoh, E.T. Kang, D.W. Pack and D.E. Leckband, "Synthesis and functionalization of polypyrrole-Fe3O4 nanoparticles for applications in biomedicine," Journal of Materials Chemistry, 17, 3354-3362 (2007).

S.C. Wuang, K.G. Neoh, E.T. Kang, D.W. Pack and D.E. Leckband, "Polypyrrole nanospheres with magnetic and cell-targeting capabilities," Macromolecular Rapid Communications, 28, 816-821 (2007).

N.K. Varde and D.W. Pack,"“Influence of particle size and antacid on release and stability of plasmid DNA from uniform PLGA microspheres," Journal of Controlled Release, 124, 172-180 (2007).

C. Berkland, E. Pollauf, N. Varde, D.W. Pack and K. Kim, "Monodisperse liquid-filled biodegradable microcapsules," Pharmaceutical Research, 24, 1007-1013 (2007).

C. Berkland, E. Pollauf, C. Raman, R. Silverman, K. Kim and D.W. Pack, "Macromolecule release from monodisperse PLG microspheres: Control of release rates and investigation of release mechanism," Journal of Pharmaceutical Sciences, 96, 1176-1191 (2007).

N.P. Gabrielson and D.W. Pack, "Acetylation of polyethylenimine enhances gene delivery via weakened polymer/DNA interactions." Biomacromolecules 7, 2427-2435 (2006).

E.J. Pollauf and D.W. Pack, "Use of thermodynamic parameters for design of polymer/polymer microcapsule systems." Biomaterials 27, 2898-2906 (2006).

E.J. Pollauf, K. Kim and D.W. Pack, "Small-molecule release from poly(d,l-lactide)/poly(d,l-lactide-co-glycolide) composite microparticles." Journal of Pharmaceutical Science 94, 2013-2022 (2005).

D.W. Pack, A.S. Hoffman, S. Pun and P. Stayton, "Design and development of polymeric gene delivery vectors." Nature Reviews Drug Discovery 4, 581-593 (2005).

C. Raman, C. Berkland, K. Kim and D.W. Pack, "Modeling small-molecule release from PLG microspheres: effects of polymer degradation and non-uniform drug distribution." Journal of Controlled Release 103, 149-158 (2005).

C. Berkland, A. Cox, K. Kim and D.W. Pack, "Three-month, zero-order piroxicam release from monodisperse double-walled microspheres of controlled shell thickness." Journal of Biomedical Materials Research 70A, 576-584 (2004).

M.L. Forrest, G.E. Meister, J.T. Koerber and D.W. Pack, "Partial acetylation of polyethylenimine enhances in vitro gene delivery." Pharmaceutical Research 21, 365-371 (2004).

N.K. Varde and D.W. Pack, "Microspheres for controlled-release drug delivery." Expert Opinion in Biological Therapy 4, 35-51 (2004).

M.L. Forrest, J.T. Koerber and D.W. Pack, "A degradable, non-toxic polyethylenimine derivative for highly efficient gene delivery." Bioconjugate Chemistry 14, 934-940 (2003).

C. Berkland, K. Kim and D.W. Pack, "PLG microsphere size controls drug release rate through several competing factors." Pharmaceutical Research 20, 1055-1062 (2003).

C. Berkland, M. King, A. Cox, K. Kim and D.W. Pack, "Precise control of PLG microsphere size provides enhanced control of drug release rate." Journal of Controlled Release 82, 137-147 (2002).