Kevin G Rice

Kevin G Rice

  • Professor, Department of Pharmaceutical Sciences and Experimental Therapeutics / Division of Medicinal and Natural Products Chemistry

Office

300

Phone

(319) 335-9903

Research Narrative

My laboratory is focused on the development and testing of non-viral gene delivery systems. This typically involves the development of peptides that either bind ionically or covalently to plasmid DNA to direct its targeting across the cell membrane and to the nucleus. We also develop glycopeptides for gene delivery, where the N-glycan mediates cell-specific targeting of DNA and receptor mediated endocytosis. The lab expertise includes solid-phase peptide synthesis, HPLC and MS, plasmid DNA and siRNA formulation, in vitro and in vivo testing of gene delivery systems and bioconjugate chemistry including N-glycan purification and PEGylation of peptides.

Curriculum vitae

Education
BS, Chemistry & Biology, Marycrest College, Davenport, Iowa, 1983
PhD, Medicinal & Natural Products Chemistry, College of Pharmacy, The University of Iowa, 1987

Professional Experience
1987-91, Postdoctoral Fellow, Department of Biology, The Johns Hopkins University, Baltimore, Maryland
1991-94,Assistant Professor of Pharmaceutics and Pharmaceutical Chemistry, College of Pharmacy, The Ohio State University, Columbus, Ohio
1995-97, Assistant Professor of Medicinal Chemistry and Pharmaceutics, College of Pharmacy, The University of Michigan, Ann Arbor, Michigan
1997-2001, Associate Professor of Medicinal Chemistry and Pharmaceutics, College of Pharmacy, The University of Michigan, Ann Arbor, Michigan
2001-2010, Professor and Division Head, Medicinal & Natural Products Chemistry, Professor of Pharmaceutics, College of Pharmacy, The University of Iowa, Iowa City, Iowa
2010-present, Professor, Medicinal & Natural Products Chemistry, Professor of Pharmaceutics, College of Pharmacy, The University of Iowa, Iowa City, Iowa

Awards
American Chemical Society Undergraduate Summer Research Fellow, Wichita State University, 1983
Dimitri V. d'Arbeloff Postdoctoral Fellow, Department of Biology, The Johns Hopkins University, 1987
National Research Service Award, Sponsored by the NIH-GMS, Department of Biology, The Johns Hopkins University, 1988
Horace S. Isbell Award, American Chemical Society, Division of Carbohydrates, 2001
Inducted into The Johns Hopkins Society of Scholars, 2003

Research
Dr. Rice's research interests are in the synthesis and testing of carrier systems for targeted gene delivery. His studies involve peptide, carbohydrate and bioconjugate synthesis, gene formulation, in vitro and vivo testing of gene delivery systems.

Representative Publications
Duskey, J.T. and Rice, K.G. Nanoparticle Ligand Presentation for Targeting Solid Tumors. AAPS PharmSciTech. (2014) 15, 1345-54. 

Ericson, M.D., Rice, K.G., and Zuber, G., "Design of Macromolecular Conjugates for Nucleic acid Delivery" in Advances in Gene Therapy, Imperial College Press, Daniel Scherman editor (2014) p 207-220.

Khargharia, S., Kizzire, K., Ericson, M.D., Baumhover, N.J., Rice, K.G. "PEG Length and Chemical Linkage Controls Polyacridine Peptide DNA Polyplex Pharmacokinetics, Biodistribution, Metabolic Stability and In Vivo Gene Expression." J Control Release. (2013) 170, 325-333.

Kizzire, K., Khargharia, K. and Rice K.G. " High-Affinity PEGylated Polyacridine Peptide Polyplexes Extend Circulatory Stability and Mediate Potent In Vivo Gene Expression" Gene Therapy, (2013) 20, 406-16.

Ericson, M.D, and Rice K.G. "Iterative Reducible Ligation to form Homogeneous Penicillamine Cross-linked Polypeptides" Tet. Lett. (2013) 54, 3440-3443.

Ericson, M.D, and Rice K.G. "A Convergent Synthesis of Homogeneous Reducible Polypeptides" Tett Lett. (2013) 54, 4746-4748.

Ericson, M., Rice, K.G., and Zuber, G., "Design of Macromolecular Conjugates for Nucleic acid Delivery" in Advances in Gene Therapy, Imperial College Press, Daniel Scherman editor (2014), p 207-220.Khargharia, S., Kizzire, K., Ericson, M.D., Baumhover, N.J., Rice, K.G. PEG length and chemical linkage controls polyacridine peptide DNA polyplex pharmacokinetics, biodistribution, metabolic stability and in vivo gene expression. J Control Release. (2013) 170, 325-33.

Ericson, M.D., Rice, K.G. Synthesis of homogenous disulfide cross-linked polypeptides by iterative reducible ligation. Biopolymers. (2012) 98, 510-7. 

Fernandez, C.A. Baumhover, N.J., Duskey, J., Khangharia, S., Kizzire, K., Ericson, M., and Rice, K.G. Metabolically Stabilized Long-Circulating PEGylated Polyacridine Peptide Polyplexes Mediate Hydrodynamically Stimulated Gene Expression in Liver. Gene Therapy (2010) 18, 23-37.

Baumhover, N. Anderson, K, Fernandez C., and Rice, K.G. Synthesis of In Vitro Testing of a Potent New Polyacridine-melittin Gene Delivery Peptides. Bioconjugate Chemistry, (2010) 21, 74-83.

Fernandez, C.A, Baumhover, N.J., Anderson, K., and Rice, K.G. Discovery of Metabolically Stabilized Electronegative Polyacridine-PEG Peptide DNA Open Polyplexes. Bioconjugate Chemistry (2010) 21, 723-30.

Anderson, K, Fernandez, C.A., and Rice, K.G. N-Glycan Targeted Gene Delivery to the Dendritic Cell SIGN Receptor. Bioconjugate Chemistry (2010) 21, 1479-85.

Ramadugu, S.K., Chung, Y.H., Fuentes, E.J., Rice, K.G. and Margulis, C.J. In Silico Prediction of the 3D Structure of Trimeric Asialoglycoprotein Receptor Bound to Triantennary Oligosaccharide. Journal of the American Chemical Society (2010) 132, 9087-95.

Fernandez, C.A. and Rice, K.G. Engineered Nanoscaled Polyplex Gene Delivery Systems. Mol Pharm. (2009) 6(5):1277-89.

Rettig, G.R. and Rice, K.G. Quantitative In Vivo Imaging of Non-viral-Mediated Gene Expression and RNAi-Mediated Knockdown. (2009) Methods in Molecular Biology, Humana Press (Preston B.Rich and ChristelleDouillet, Ed.) 574,155-71.

Martin, M.E. and Rice, K.G. A Novel Class of Intrinsic Proteasome Inhibitory Gene Transfer Peptides. Bioconj Chem. (2008) 19(1):370-376.

Rettig, G.R. and Rice, K.G. Non-viral gene delivery: from the needle to the nucleus. Expert Opin Biol Ther. (2007) 7(6):799-808.

Chen, C.P., Kim, J.S., Liu, D., Rettig, G.R., McAnuff, M.A., Martin, M.E., and Rice, K.G. Synthetic PEGylated Glycoproteins and their Utility in Gene Delivery. Bioconj. Chem. (2007) 18(2):371-8.

McAnuff, M.A., Rettig, G.R., and Rice, K.G. Potency of siRNA versus shRNA Mediated Knockdown in Vivo. J. Pharm. Sci. (2007) 96(11):2922-2930.

Martin, M.E. and Rice, K.G. Peptide Guided Gene Delivery. AAPS J. (2007) 9(1):E18-29.

Rettig, G.R., McAnuff, M., Liu, D., Kim, J.S., and Rice, K.G. Quantitative Bioluminescence Imaging of Transgene Expression In Vivo. Anal. Biochem. (2006) 335(1):90-94.

Chen, C.P., Kim, J.S., Steenblock, E., Liu, D., and Rice, K.G. Gene Transfer with Poly-melittin Peptides. Bioconj. Chem., (2006) 17(4):1057-1062.

Oyewumi, M.O. and Rice, K.G. “DNA Nanoparticle Gene Delivery Systems” in Nanotechnology for Drug Delivery, Marcel Dekker, Inc., Eds, R.B. Gupta and U.B. Kompella. (2006) Ch. 12, pp. 361-379.

Huang, Y.C., Riddle, K., Rice K.G., and Mooney, D.J. Long-term In Vivo Gene Expression via Delivery of PEI-DNA Condensates from Porous Polymer Scaffolds. Hum Gene Ther (2005) 16(5):609-617.

Huang, Y.C., Simmons, C., Kaigler, D., Rice, K.G., and Mooney, D.J. Bone Regeneration in a Rat Cranial Defect with Delivery of PEI-Condensed Plasmid DNA Encoding for Bone Morphogenetic Protein-4 (BMP-4). Gene Ther (2005) 12(5):418-426.

Kim, J., Chen, C.P. and Rice, K.G. The Proteasome Metabolizes Peptide-Mediated Nonviral Gene Delivery Systems. Gene Ther., (2005) 12(21):1581-90.

Huang, Y.C., Kaigler, D., Rice, K.G., Krebsbach P.H., and Mooney, D.J. Combined angiogenic and osteogenic factor delivery enhances bone marrow stromal cell-driven bone regeneration. J. Bone and Miner Res (2005) 20(5):848-57.

Elhalabi, J. and Rice, K.G. Synthesis of Uridine 5’-[2-S-pyridyl-3-thio-a-D-galactopyranosyl diphosphate]: Precursor of UDP-Thiogal Sugar Nucleotide Donor Substrate for b-1,4-Galactosyltransferase. Nucleosides, Nucleotides & Nucleic Acids (2004) 23(1-2):195-205.

Thanawiroon, C., Rice, K.G., Toida, T., and Linhardt, R.J. Liquid Chromatography/Mass Spectrometry Sequencing Approach for Highly Sulfated Heparin-derived Oligosaccharides. J. Biol. Chem. (2004) 279(4):2608-2615.

Chen, C.P., Park, Y. and Rice, K.G. An Improved Large-Scale Synthesis of PEG-Peptides for Gene Delivery. J. Pept Res (2004) 64(6):237-243.

Rice, K.G., Kim, J.S., and Liu, D. “Glycopolymers: Tools for Studying Targeted Non-viral Gene Delivery” in Polymeric Gene Delivery, (Mansoor M. Amiji Ed.) CRC Press (2004) pp. 509-521.

Kwok, K.Y., Park, Y., Yang, Y., McKenzie, D.L., Liu, Y. and Rice, K.G. In Vivo Gene Transfer using Sulfhydryl Cross-linked PEG-peptide/Glycopeptide DNA Co- Condensates. J. Pharm. Sci. (2003) 92(6):1174-1185.

Huang, Y.C., Connell, M., Park, Y., Mooney, D.J. and Rice, K.G. Fabrication and In Vitro Testing of a Polymeric Delivery System for Condensed DNA. J. Biomed. Mater. Res. (2003) 67(4):1384-1392.

Rice, K.G., Thomas, V.H. and Yang, Y. Probing the Binding Specificity of C-Type Lectins In Vivo. Methods Enzymol. (2003) 363:90-104.

Park, Y., Kwok, K.Y., Boukarim, C. and Rice, K.G. Synthesis of Sulfhydryl Cross-linking Poly(ethylene glycol)-Peptides and Glycopeptides as Carriers for Gene Delivery. Bioconj. Chem. (2002) 13(2):232-239.

Elhalabi, J. and Rice, K.G. Thiosugar Nucleotide Analogs: Synthesis of 5’-(2,3,4-tri-O-acetyl-6-S-acetyl-6-thio-alpha-D-galactophyranosyl diphosphate). Carbohydr. Res. (2002) 337(21-23):1935-1940.

Rice, K.G. "Preparative Purification and Utilization of Tyrosinamide N-Glycan Libraries" in Carbohydrate Analysis by Modern Chromatography and Electrophoresis, Journal of Chromatography Library, Elsevier, Amsterdam, The Netherlands, (2002) Vol 66, pp 535-570.

Kwok, K.Y., Yang, Y.S., and Rice, K.G. Evolution of Cross-linked Non-viral Gene Delivery Systems. Curr Opin Mol Ther (2001) 3(2):142-146.

Yang, Y., Park, Y., Man, S., Liu, Y. and Rice, K.G. Cross-linked Low Molecular Weight Glycopeptide-Mediated Gene Delivery: Relationship between DNA Metabolic Stability and the Level of Transient Gene Expression In Vivo. J. Pharm. Sci. (2001) 90(12):2010-2022.

Elhalabi, J. and Rice, K.G. Thiosugar nucleotide analogues: synthesis of uridine 5`-(2,3,6-tri-O-acetyl-4-S-acetyl-4-thio-alpha-D-galactopyranosyl diphosphate). Carbohydr. Res. (2001) 335(3):159-165.

Rice, K.G. Application of Fluorescence Resonance Energy Transfer to Analyze Carbohydrates. Anal. Biochem. (2001) 297(2):117-122.

Collard, W.T., Evers, D. L. McKenzie D.L. and Rice, K. G. Synthesis of Homogenous Glycopeptides as DNA Targeting Agents. Carbohydr. Res. (2000) 323(1-4):176-184.

Collard, W.T., Yang, Y., Kwok, K.Y., Park, Y. and Rice, K.G. Biodistribution, Metabolism, and In Vivo Gene Expression of Low Molecular Weight Glycopeptide Polyethylene glycol DNA Co-Condensates. J. Pharm. Sci. (2000) 89(4): 499-511.

McKenzie, D.L., Kwok, K.Y. and Rice, K.G. A Potent New Class of Reductively Activated Peptide Gene Delivery Agents. J. Biol. Chem. (2000) 275(14):9970-9977.

Rice, K.G. Derivatization Strategies for Preparing N-Glycan Probes. Anal. Biochem. (2000) 283(1):10-16.

Kwok, K.Y., Adami, R.C., Hester, K.C., Park, Y., Thomas, S., and Rice, K.G. Strategies for Maintaining the Particle Size of Peptide DNA Condensates Following Freeze-drying. Int. J. Pharm. (2000) 203(1-2):81-88.

McKenzie, D.L., Smiley, E., Kwok, K.Y., and Rice, K.G. Low Molecular Weight Disulfide Cross-linking Peptides as Nonviral Gene Delivery Carriers. Bioconj. Chem. (2000) 11(6):901-909.

Yang, Y.S., Thomas, V.H., and Rice, K.G. Tissue Targeting of Multivalent GalNAc-Lex Terminated N-glycans in Mice. Glycobiology (2000) 10(12):1341-1345.