Projektbeschreibung
Trojanisches Pferd zur Behandlung entzündlicher Darmerkrankungen
Entzündliche Darmerkrankungen sind durch chronische Entzündungen des Darms gekennzeichnet. Ungeachtet ihrer steigenden Prävalenz ist die genaue Ätiologie immer noch unbekannt. Um die Behandlungsergebnisse bei von entzündlichen Darmerkrankungen Betroffenen zu verbessern, lauter das Ziel des EU-finanzierten Projekts LeukoTheranostics, die Immunzellen, die für die beobachtete Darmentzündung verantwortlich sind, gezielt zu bekämpfen. Die Forschenden werden Nanopartikel entwickeln, die RNS-Interferenzmoleküle als therapeutische Behandlung enthalten und auf ein spezifisches Protein abzielen, das auf der Oberfläche von Darm-Leukozyten exprimiert wird. Das Team wird Mäusemodelle für entzündliche Darmerkrankungen anwenden, um die Nanopartikel in vivo nachzuverfolgen und ihre Wirksamkeit zu bewerten, und auf diese Weise einer innovativen Behandlung für entzündliche Darmerkrankungen von hohem klinischem Wert den Weg bereiten.
Ziel
"Inflammatory bowel diseases (IBD) is a group of chronic inflammatory conditions of the gastrointestinal tract, including Crohn’s disease (CD) and Ulcerative Colitis (UC) that can impact both the large and small bowel. IBD affects approximately 3.7 million Europeans and its peak onset is in persons of 15 to 30 years of age. IBD imposes a significant burden on Europe with over €3B in annual health care costs and over €3B in indirect cost. The prevalence of IBD is expected to increase by more than 40% over the next decade in many European countries. Therefore, to meet the needs of IBD patients in the European community, we must prepare for the evolving landscape of IBD care in the near future. Although its etiology remains unknown, unregulated immune cells are implicated in the pathogenesis of IBD. As many IBD patients are refractory to conventional medical treatments, there is an urgent need to develop novel therapeutic modalities in combination with real-time imaging in order to manage the disease. I will achieve this goal by generating a ""Trojan horse"" strategy of targeting activated leukocytes that home to the gut in IBD rodent models and reprogram their fate using RNA interference (RNAi) combined with molecular imaging.
The primary objective of this proposal is to reprogram in vivo activated leukocytes involved in gut inflammation using advanced RNAi-based therapeutics combined with molecular imaging strategies as the first theranostic modality utilizing leukocytes. The following specific aims include: (i) To develop and characterize unique integrin-targeted nanoparticles (I-tsNPs) targeting a high-affinity (HA) conformation of a4b7 integrin expressed on gut leukocytes; (ii) To study I-tsNPs 3-dimensional (3-D) delivery in colitis models using microPET/CT imaging; (iii) To investigate efficacy and safety profiles using the HA I-tsNPs platform for IBD therapeutics and disease management that will lay the foundation for future clinical trials.
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Wissenschaftliches Gebiet
- medical and health sciencesclinical medicinegastroenterologyinflammatory bowel disease
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteins
- medical and health sciencesbasic medicineimmunology
- natural sciencesbiological sciencesbiochemistrybiomoleculeslipids
- engineering and technologynanotechnologynano-materials
Programm/Programme
Thema/Themen
Finanzierungsplan
ERC-COG - Consolidator GrantGastgebende Einrichtung
69978 Tel Aviv
Israel