Eparations through spinoculation, and GFP fluorescence was measured by flow cytometry to figure out infection levels after 72 h. Final results: Our engineered anti-HIV scFv-decorated exosomes substantially inhibited HIV infection in Jurkat cells with respect to all unfavorable controls (n = 3; p 0.05, paired t-test). Anti-HIV scFv-decorated exosomes potently inhibited HIV infection in principal human CD4 + T cells (n = two donors) within a dose-dependent manner, suppressing up to 87 of infection in the absence of toxicity. Summary/Conclusion: Engineering exosomes ex vivo MMP-13 MedChemExpress represents a promising therapeutic approach for HIV infection. Future work will test the capacity of our designer exosomes to inhibit HIV replication in vivo in humanized mouse models. Beyond viral suppression, we’ll determine if designer exosomes can accelerate the clearance of HIV latently-infected cells, the main obstacle to a cure for HIV infection. Funding: NIH P01AI131374 and R01GMPT11.Exosome-mediated RNAi of PAK4 prolongs survival of pancreatic cancer mouse model soon after loco-regional treatment Lizhou Xua, Julie Wangb, Farid N. Faruqub, Kee Limb, Adam Waltersb, Claire Wellsb and Khuloud Al-Jamalba School of Cancer and Pharmaceutical Sciences, King’s College TLR8 review London, London, UK; bKing’s College London, London, UKIntroduction: Pancreatic cancer (Pc) remains one of the most aggressive and devastating malignancies, predominantly because of the absence of a valid biomarker for diagnosis and limited therapeutic possibilities for advanceddisease. Exosomes (Exo) as cell-derived vesicles are widely applied as organic nanocarriers for drug delivery. P21-activated kinase 4 (PAK4) is oncogenic when overexpressed, promoting cell survival, migration and anchorage-independent development. In this study, we validate PAK4 as a therapeutic target in an in vivo Pc tumour mouse model making use of Exo nanocarriers following intra-tumoural administration. Procedures: Pc derived Exo were firstly isolated by ultracentrifugation on sucrose cushion and characterized for their surface marker expression, size, number, purity and shape. siRNA was encapsulated into Exo via electroporation and dual uptake of Exo and siRNA was investigated by flow cytometry and confocal microscopy. In vitro siPAK4 silencing in Computer cells was assessed by western blotting, flow cytometry, and in vitro scratch assay. In vivo efficacy (tumour development delay and mouse survival) of siPAK4 was evaluated in Pc bearing NSG mouse model. Ex vivo tumours had been examined applying Haematoxylin and eosin (H E) staining and immunohistochemistry. Final results: Good quality Pc derived PANC-1 Exo had been obtained. siRNA was incorporated in Exo with 16.5 loading efficiency. Exo and siRNA co-localization in cells was confirmed by in vitro imaging. PAK4 knock-down was effective at 30 nm Exo-siPAK4 at 24 h post-incubation in vitro. Intra-tumoral administration of Exo-siPAK4 (1 siPAK4 and 7.7 1011 Exo, each dose, two doses) decreased Pc tumour development and enhanced mice survival (p 0.001), with minimal toxicity observed in comparison with polyethylenimine (PEI) applied as a industrial transfection reagent. H E staining of tumours showed important tissue apoptosis in siPAK4 treated groups. Summary/Conclusion: PAK4 interference prolongs survival of Pc bearing mice suggesting its candidacy as a new therapeutic target in Pc. PANC-1 Exo demonstrated comparable efficacy but safer profile than PEI as in vivo RNAi transfection reagent. Funding: The K. C. Wong Education Foundation plus the Marie Sklodowska-Curie ac.