Hans Herweijer
Mirus Bio
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Publication
Featured researches published by Hans Herweijer.
Nucleic Acids Research | 2006
Angus T. De Souza; Xudong Dai; Andrew G. Spencer; Tom W. Reppen; Ann Menzie; Paula L. Roesch; Yudong He; Michelle Caguyong; Sherri Bloomer; Hans Herweijer; Jon A. Wolff; James E. Hagstrom; David L. Lewis; Peter S. Linsley; Roger G. Ulrich
RNA interference (RNAi) has great potential as a tool for studying gene function in mammals. However, the specificity and magnitude of the in vivo response to RNAi remains to be fully characterized. A molecular and phenotypic comparison of a genetic knockout mouse and the corresponding knockdown version would help clarify the utility of the RNAi approach. Here, we used hydrodynamic delivery of small interfering RNA (siRNA) to knockdown peroxisome proliferator activated receptor alpha (Ppara), a gene that is central to the regulation of fatty acid metabolism. We found that Ppara knockdown in the liver results in a transcript profile and metabolic phenotype that is comparable to those of Ppara−/− mice. Combining the profiles from mice treated with the PPARα agonist fenofibrate, we confirmed the specificity of the RNAi response and identified candidate genes proximal to PPARα regulation. Ppara knockdown animals developed hypoglycemia and hypertriglyceridemia, phenotypes observed in Ppara−/− mice. In contrast to Ppara−/− mice, fasting was not required to uncover these phenotypes. Together, these data validate the utility of the RNAi approach and suggest that siRNA can be used as a complement to classical knockout technology in gene function studies.
Journal of Gene Medicine | 2008
Christine I. Wooddell; Thomas W. Reppen; Jon A. Wolff; Hans Herweijer
To properly study gene expression in vivo, often long‐term expression is desired. Previous studies using plasmid DNA (pDNA) vectors have typically resulted in short‐term expression. Here, we evaluated combinations of the albumin promoter with different enhancers and untranslated regions for liver‐specific expression in mice.
Cancer Immunology, Immunotherapy | 2007
Zane C. Neal; Paul M. Sondel; Mary Kay Bates; Stephen D. Gillies; Hans Herweijer
Therapeutic treatment with hu14.18-IL-2 immunocytokine (IC) or Flt3-L (FL) protein is initially effective at resolving established intradermal NXS2 neuroblastoma tumors in mice. However, many treated animals develop recurrent disease. We previously found that tumors recurring following natural killer (NK) mediated IC treatment show augmented MHC class I expression, while the tumors that recurred following T cell dependent Flt3-L treatment exhibited decreased MHC class I expression. We hypothesized that this divergent MHC modulation on recurrent tumors was due to therapy-specific immunoediting. We further postulated that combining IC and Flt3-L treatments might decrease the likelihood of recurrent disease by preventing MHC modulation as a mechanism for immune escape. We now report that combinatorial treatment of FL plus hu14.18-IL-2 IC provides greater antitumor benefit than treatment with either alone, suppressing development of recurrent disease. We administered FL by gene therapy using a clinically relevant approach: hydrodynamic limb vein (HLV) delivery of DNA for transgene expression by myofibers. Delivery of FL DNA by HLV injection in mice resulted in systemic expression of >10xa0ng/ml of FL in blood at dayxa03, and promoted up to a fourfold and tenfold increase in splenic NK and dendritic cells (DCs), respectively. Furthermore, the combination of FL gene therapy plus suboptimal IC treatment induced a greater expansion in the absolute number of splenic NK and DCs than achieved by individual component treatments. Mice that received combined FL gene therapy plus IC exhibited complete and durable resolution of established NXS2 tumors, and demonstrated protection from subsequent rechallenge with NXS2 tumor.
Archive | 2002
Hans Herweijer; Vladimir G. Budker
Biochemical and Biophysical Research Communications | 2005
Christine I. Wooddell; Cristopher V. Van Hout; Thomas W. Reppen; David L. Lewis; Hans Herweijer
Archive | 1999
Jon A. Wolff; Hans Herweijer; Larry F. Whitesell; Matthew R. Wolff; Sean D. Monahan; Paul M. Slattum; James E. Hagstrom; Vladimir G. Budker; David B. Rozema
Molecular Therapy | 2007
Zane C. Neal; Mary Kay Bates; Mark R. Albertini; Hans Herweijer
Chemistry & Biology | 2007
Sean D. Monahan; Vladimir Subbotin; Vladimir G. Budker; Paul M. Slattum; Zane C. Neal; Hans Herweijer; Jon A. Wolff
PLOS Computational Biology | 2005
Xudong Dai; Angus T. De Souza; Hongyue Dai; David L. Lewis; Chang-kyu Lee; Andrew G. Spencer; Hans Herweijer; Jim E Hagstrom; Peter S. Linsley; Douglas E. Bassett; Roger G. Ulrich; Yudong D. He
Archive | 2004
Jon A. Wolff; Vladimir G. Budker; James E. Hagstrom; Hans Herweijer; Julia O. Hegge