BEGIN:VCALENDAR VERSION:2.0 PRODID:-//Memento EPFL// BEGIN:VEVENT SUMMARY:BioE COLLOQUIA SERIES: "Design of siRNA-Loaded Lipidoid-Polymer H ybrid Nanoparticles for Local RNAi-Based Treatment of Chronic Obstructive Pulmonary Disease (COPD)" DTSTART:20191104T121500 DTSTAMP:20260916T064651Z UID:b5b2ce1621e0bf16a7f4eb36b852e60aca0333b9886d709b69c34d35 CATEGORIES:Conferences - Seminars DESCRIPTION:Prof. Camilla Foged\, University of Copenhagen (DK)\nWEEKLY BI OENGINEERING COLLOQUIA SERIES\n(sandwiches served)\n\nAbstract: \nTherapeu tics based on RNA interference (RNAi) are highly target-specific and promi sing for the treatment of serious diseases lacking definite clinical manag ement\, e.g. chronic obstructive pulmonary disease (COPD)\, characterized by persistent airflow limitation and chronic airway inflammation\, progres sively leading to loss of airway function. The cytokine tumor necrosis fac tor (TNF)-α released by macrophages is associated with active inflammatio n during COPD. Currently\, no single\, definitive therapy exists against C OPD. However\, targeting cytokines via the RNA interference (RNAi) pathway is one approach for management of the early inflammatory phase in COPD. R NAi is mediated by small interfering RNA (siRNA)\, which is capable of ind ucing selective and highly potent gene silencing. However\, intracellular delivery of siRNA to the RNAi pathway in the cytosol remains a challenge. The efficacy of siRNA therapeutics is fully dependent on technologies that safely can facilitate intracellular delivery. We have made a major breakt hrough by inventing a delivery technology based on well-tolerated lipidoid -polymer hybrid nanoparticles (LPNs) with an unprecedented ability to deli ver siRNA to target tissues (1\,2). This technology is ten times more effi cient than state-of-the-art delivery systems and thus allows for dose redu ction\, which improves the safety profile and reduces cost of goods. We ar e using LPNs to silence key genes involved in COPD. We have proof-of-conce pt in vivo that LPNs loaded with siRNA against TNF-α can reduce experimen tal inflammation. This presentation focusses on how we solve fundamental s cientific and technical preclinical challenges necessary for the further d esign and progression of the siRNA-loaded LPNs from the preclinical stage towards clinical testing. In particular\, I will focus on (i) how we have applied a quality-by-design-based approach for the design and optimization of TNF-α siRNA-loaded LPNs for local RNAi-based treatment of COPD\, and (ii) how to scale up the manufacture of powder-based dosage forms with pro perties suitable for inhalation (3). In addition\, I will present data pro viding a mechanistic profiling of the release kinetics of siRNA from LPNs in vitro and in vivo after pulmonary administration (4). This knowledge co ntributes significantly to increasing our understanding of the basic requi rements for controlling and sustaining the delivery of the siRNA cargo to lung tissue for local management of disease.\n \nReferences:\n1. Thanki K \, Zeng X\, Justesen S\, Tejlmann S\, Falkenberg E\, Van Driessche E\, Nie lsen HM\, Franzyk H\, Foged C. Engineering of small interfering RNA-loaded lipidoid-poly(DL-lactic-co-glycolic acid) hybrid nanoparticles for highly efficient and safe gene silencing: A quality by design-based approach. Eu r J Pharm Biopharm. 2017\;120:22-33.\n2. de Groot AM\, Thanki K\, Gangloff M\, Falkenberg E\, Zeng X\, van Bijnen DCJ\, van Eden W\, Franzyk H\, Nie lsen HM\, Broere F\, Gay NJ\, Foged C\, Sijts AJAM. Immunogenicity Testing of Lipidoids In Vitro and In Silico: Modulating Lipidoid-Mediated TLR4 Ac tivation by Nanoparticle Design. Mol Ther - Nucleic Acids. 2018\;11:159-16 9.\n3. Dormenval C\, Lokras A\, Cano-Garcia G\, Wadhwa A\, Thanki K\, Rose F\, Thakur A\, Franzyk H\, Foged C. Identification of Factors of Importan ce for Spray Drying of Small Interfering RNA-Loaded Lipidoid-Polymer Hybri d Nanoparticles for Inhalation. Pharm Res. 2019\;36(10):142.\n4. Thanki K\ , van ED\, Geyer A\, Fraire J\, Hendrix R\, Van EH\, Putteman E\, Sami H\, de SC-W\, Franzyk H\, Nielsen HM\, Braeckmans K\, Lehr CM\, Ogris M\, Fog ed C. Mechanistic profiling of the release kinetics of siRNA from lipidoid -polymer hybrid nanoparticles in vitro and in vivo after pulmonary adminis tration. J Control Release. 2019\;310:82-93.\n\nBio:\nCamilla Foged is Ful l Professor of Vaccine Design and Delivery at the Department of Pharmacy a t University of Copenhagen (since 2018)\, Denmark. Her main research area is advanced drug delivery\, in particular design of new vaccine and nuclei c acid delivery systems to improve therapy. Drug delivery challenges are a ddressed using state-of-the-art technologies\, and this has fostered innov ative solutions and high-impact publications in drug delivery. Her researc h goal is to improve disease prevention and treatment in the fields of inf ectious and inflammatory diseases and cancer. These aims are approached by imaging-guided design of nanoparticle-based vaccine and nucleic acid form ulations\, and she engages in research projects spanning from early discov ery phase projects to first-in-man clinical studies. She is widely recogni zed nationally and internationally in the field of drug delivery\, and she has a well-established and extensive network of national and internationa l collaborators in academia and industry. Her research has been funded wit h more than EUR 8 million via prestigious and highly competitive grants. S he has an MSc in Biochemistry from University of Copenhagen (1998)\, and s he attained her PhD in Pharmaceutics in 2003 from The Danish University of Pharmaceutical Sciences. Prof. Foged has edited one book about subunit va ccine delivery\, and she has (co)authored more than 110 scientific papers/ book chapters and 175 conference abstracts at national and international c onferences.\n\nZoom link for attending remotely: https://epfl.zoom.us/j/46 1567156 LOCATION:SV 1717 https://plan.epfl.ch/?room==SV%201717 STATUS:CONFIRMED END:VEVENT END:VCALENDAR