Chemical & Biomolecular Engineering Department of Chemical and Biomolecular Engineering University of Illinois University of Illinois at Urbana - Champaign
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School of Chemical Sciences   |   College of Liberal Arts & Sciences  |   College of Engineering

 

Daniel W. Pack

Daniel W. Pack
Pack Group Web Site

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

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

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

N.P. Gabrielson and D.W. Pack, "Efficient polyethylenimine-mediated gene delivery proceeds via a caveolar pathway in HeLa cells," J. Controlled Release, 136, 54-61 (2009).

J.G. Hardy, C.S. Love, N.P. Gabrielson, D.W. Pack and D.K. Smith, "Synergistic effects on gene delivery - co-formulation of small disulfide-linked dendritic polycations with Lipofectamine 2000 (TM)," Organic & Biomolecular Chemistry, 7, 789-793 (2009).

C.J. Park, N.P. Gabrielson, D.W. Pack, R.D. Jamison and A.J.W. Johnson, "The effect of chitosan on the migration of neutrophil-like HL60 cells, mediated by IL-8," Biomaterials, 30, 436-444 (2009).

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

D.M. Drake and D.W. Pack, "Biochemical investigation of active intracellular transport of polymeric gene-delivery vectors," J. Pharm. Sci., 97, 1399-1413 (2008).

S.C. Wuang, K.G. Neoh, E.T. Kang, D.W. Pack and D.E. Leckband, "HER-2-mediated endocytosis of magnetic nanospheres and the implications in cell targeting and particle magnetization," Biomaterials, 29, 2270-2279 (2008).

S.P. Jones, N.P. Gabrielson, D.W. Pack and D.K. Smith, "Synergistic effects in gene delivery - a structure-activity approach to the optimisation of hybrid dendritic-lipidic transfection agents," Chem. Comm., 4700-4702 (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," J. 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," J. Mat. Chem., 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," J. 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," J. Pharm. Sci., 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." J. Pharm. Sci., 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." J. Controlled Release, 103, 149-158 (2005).