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Viruses and Nanobiology Active compounds • Antiviral Drugs • siRNA • miRNA • DNA Access to “viral sanctuaries” (CNS, lymph nodes, tissue) HIV FIV 1. 2. 3. 4. 5. 6. 7. Ability to efficiently access tissues Ability to traverse the blood brain barrier Solubility, Toxicity, Concentration Rate of release Protection of active compounds (siRNA, miRNA, labile compounds) Specific targeting of infected cells (particles coating) Combination of antivirals at lower doses reducing therapy-related side-effects Active compounds Nanoparticles Lymph nodes Advantages of encapsulating active compounds in nanoparticles Brain Lungs HIV FIV Air borne and respiratory viruses HIV FIV Viruses and Nanobiology Experimental plan Enhancing the efficiency of antiviral drug delivery Active compounds Nanoparticles Active compounds • Currently available and potential new Antiviral Drugs • siRNA • miRNA • DNA •One of the central features of HIV infection is that, in addition to targeting CD4 T-cells, the virus has the ability to infect the long-lived cell subset of the monocyte-macrophage lineage. While Tcells are quickly killed by the infection, this cellular subset appears to be the main reservoir for active virus replication even under highly active antiretroviral therapies. •Resident macrophages are found deep into tissues where drug availability is reduced and more importantly in the brain (microglia) where drugs are excluded by the blood brain barrier AIMS: Periphery•Deliver active compounds into difficult to access tissues •Specifically target infected cells CNS•Ability and kinetics of “in brain” delivery •Efficiency of combination therapies in the brain