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2016|17 Annual Report Fraunhofer IGB - Drug discovery and delivery: focus on infection, inflammation and innate immunity

3 NP accumulation at the target site, both long circulation time and eficient particle targeting are critical. True molecular targeting of liposomes can be achieved through ligand link- age to appropriately designed ‘stealth’ NP by our partners [2]. Targeting will be designed speciically to the indications mentioned above. In vitro and in vivo test systems Infection models are available for both fungal and viral infec- tions at Fraunhofer IGB [4 – 6]. These models are used to vali- date the new immune-modulating compounds as well as the formulations. In a irst step, we use cell-based assays [1, 3] to validate the PRR-modulating activity of the compounds identi- ied in silico experimentally (as mentioned above); second, we use complex 3D-tissue models, including components of the immune system [4] to validate both the effect of the IMC on different cell types including immune cells and the formulation in delivering the compounds appropriately. Animal models for further validation of the lead compounds of these indications are available with our partners. CT NT 4 Contact Dr. rer. nat. Anke Burger-Kentischer Phone +49 711 970-4023 anke.burger-kentischer@ igb.fraunhofer.de apl. Prof. Dr. rer. nat. Steffen Rupp Phone +49 711 970-4045 steffen.rupp@igb.fraunhofer.de Literature [1] Zatsepin, M. et al. (2016) J Chem Inf Model 56: 1835 – 1846 [2] Ron-Doitch, S. et al. (2016) J Control Release 229: 163 – 171 [3] Burger-Kentischer, A. et al. (2010) Journal of immunological methods 358: 93 – 103 Outlook [4] Kühbacher, A. et al. (2017) Methods in molecular biology With this approach, we aim to combine two central ideas sup- porting the healing processes in infection and inlammatory diseases: (i) modulating innate immunity by supporting clear- ance of invading pathogens or ameliorating the (auto)inlam- matory process and (ii) targeted delivery of known and novel drugs to infected or pathologically-modiied tissues / cells. 1508: 439 – 449 [5] Hogk, I. et al. (2013) Methods in molecular biology 1064; 239 – 251 [6] Hogk, I. et al. (2013) BioResearch open access 2: 250 – 257 Funding We would like to thank the Fraunhofer-Gesellschaft and the He- brew University for funding the project “Joint Research Hub for Drug Discovery and Delivery” within the ICON program. 1 Cell-based reporter gene assay in cell-culture plates. Project partners 2 The cell-based reporter gene assay is a tool to Gershon Golomb, Amiram Goldblum, Hebrew University, Jerusa- identify lead compounds for drug development. lem, Israel 3 Cell culture lasks. 4 Structure of the human TLR9 when bound to the antagonist oligodeoxynucleotide (receptor- antagonist-complex). 61

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