Markus Hossbach
Hoffmann-La Roche
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Publication
Featured researches published by Markus Hossbach.
Molecular Therapy | 2013
Christine I. Wooddell; David B. Rozema; Markus Hossbach; Matthias John; Holly Hamilton; Qili Chu; Julia Hegge; Jason Klein; Darren H. Wakefield; Claudia E. Oropeza; Jochen Deckert; Ingo Roehl; Kerstin Jahn-Hofmann; Philipp Hadwiger; Hans Peter Vornlocher; Alan McLachlan; David L. Lewis
RNA interference (RNAi)-based therapeutics have the potential to treat chronic hepatitis B virus (HBV) infection in a fundamentally different manner than current therapies. Using RNAi, it is possible to knock down expression of viral RNAs including the pregenomic RNA from which the replicative intermediates are derived, thus reducing viral load, and the viral proteins that result in disease and impact the immune systems ability to eliminate the virus. We previously described the use of polymer-based Dynamic PolyConjugate (DPC) for the targeted delivery of siRNAs to hepatocytes. Here, we first show in proof-of-concept studies that simple coinjection of a hepatocyte-targeted, N-acetylgalactosamine-conjugated melittin-like peptide (NAG-MLP) with a liver-tropic cholesterol-conjugated siRNA (chol-siRNA) targeting coagulation factor VII (F7) results in efficient F7 knockdown in mice and nonhuman primates without changes in clinical chemistry or induction of cytokines. Using transient and transgenic mouse models of HBV infection, we show that a single coinjection of NAG-MLP with potent chol-siRNAs targeting conserved HBV sequences resulted in multilog repression of viral RNA, proteins, and viral DNA with long duration of effect. These results suggest that coinjection of NAG-MLP and chol-siHBVs holds great promise as a new therapeutic for patients chronically infected with HBV.
Scientific Reports | 2016
Ci Real; Mengji Lu; Jia Liu; Xuan Huang; M. Trippler; Markus Hossbach; Jochen Deckert; Kerstin Jahn-Hofmann; L. Ickenstein; Matthias John; Kathrin Gibbert; Ulf Dittmer; Hans Peter Vornlocher; Reinhold Schirmbeck; Guido Gerken; Joerg F. Schlaak; R. Broering
The hepatitis B virus (HBV) has been described as stealth virus subverting immune responses initially upon infection. Impaired toll-like receptor signaling by the HBV surface antigen (HBsAg) attenuates immune responses to facilitate chronic infection. This implies that HBV replication may trigger host innate immune responses in the absence of HBsAg. Here we tested this hypothesis, using highly replicative transgenic mouse models. An HBV replication-dependent expression of antiviral genes was exclusively induced in HBsAg-deficient mice. These interferon responses attributed to toll-like receptor 3 (TLR3)-activated Kupffer and liver sinusoidal endothelial cells and further controlled the HBV genome replication. However, activation of TLR3 with exogenous ligands indicated additional HBs-independent immune evasion events. Our data demonstrate that in the absence of HBsAg, hepatic HBV replication leads to Tlr3-dependent interferon responses in non-parenchymal liver cells. We hypothesize that HBsAg is a major HBV-mediated evasion mechanism controlling endogenous antiviral responses in the liver. Eradication of HBsAg as a therapeutic goal might facilitate the induction of endogenous antiviral immune responses in patients chronically infected with HBV.
Archive | 2012
Daniel J. Chin; Jochen Deckert; Markus Hossbach; Matthias John
Archive | 2009
Birgit Bramlage; Rainer Constien; Jacques Himber; Markus Hossbach; Pamela Tan; Hans-Peter Vornlocher
Archive | 2009
Birgit Bramlage; Markus Hossbach; Pamela Tan; Hans-Peter Vamlocher
Archive | 2010
John Frederick Boylan; Birgit Bramlage; Wei He; Markus Hossbach; Ingo Roehl
Archive | 2011
John Frederick Boylan; Birgit Bramlage; Markus Hossbach
Archive | 2010
Jacques Bailly; Agnès Bénardeau; Birgit Bramlage; Rainer Constien; Andrea Forst; Markus Hossbach; Brigitte Schott
Archive | 2010
Birgit Bramlage; Rainer Constien; Andrea Forst; Markus Hossbach; Cristina M. Rondinone; Hans-Peter Vornlocher
Archive | 2017
Markus Hossbach; Monika Krampert; Hans-Lothar Arth