To study the function of Mfsd8, we validated a publically available mfsd8- cell line (GWDI Project) and then used this knockout cell line to show that Mfsd8 influences the secretion of Cln5 and CtsD. This information is then integrated into an emerging model describing the molecular networking of NCL proteins in Dictyostelium. In total, this study identifies Dictyostelium as a new model system for studying CLN7 disease. Sepsis is a complex disorder with very high morbidity and mortality; it can occur when an immune disorder triggers an invasion of pathogens in the host. Although many potential anti-infective and immunosuppressive treatments have been reported, we still do not have effective means of treating sepsis in clinic. The aim of this study is to develop a nanomaterial system that targets the site of inflammation and carries a combination of multiple drugs to better treat sepsis and alleviate its symptoms. We selected poly(lactide-co-glycolide acid) (PLGA) with good biocompatibility and degradability to prepare the nanoparticles (NPs) loaded with broad-spectrum antibiotic Sparfloxacin (SFX) and anti-inflammatory immunosuppressant Tacrolimus (TAC) by an emulsion-solvent evaporation method. The targeting ability of the NPs toward inflammatory sites is endowed by grafting of the γ3 peptide (NNQKIVNLKEKVAQLEA) that can specifically bind to the intercellular adhesion molecule-1 (ICAM-1), which is highly expressed on the surface of inflammatory endothelial cells. The drug loaded γ3-PLGA NPs have excellent cytocompatibility, low hemolysis ratio, and systemic toxicity. The drug loaded γ3-PLGA NPs also have excellent antibacterial property to both Gram-positive and Gram-negative bacteria and can effectively reduce the inflammation and immune response in acute lung infection mice. This study provides a simple and robust nanoplatform to treat lung infection induced sepsis, which may pave a way to design multifunctional nanomedicine for clinical translation. In 1998, the RNA interference discovery by Fire and Mello revolutionized the scientific and therapeutic world. They showed that small double-stranded RNAs, the siRNAs, were capable of selectively silencing the expression of a targeted gene by degrading its mRNA. Very quickly, it appeared that the use of this natural mechanism was an excellent way to develop new therapeutics, due to its specificity at low doses. However, one major hurdle lies in the delivery into the targeted cells, given that the different extracellular and intracellular barriers of the organism coupled with the physico-chemical characteristics of siRNA do not allow an efficient and safe administration. selleck products The development of nanotechnologies has made it possible to counteract these hurdles by vectorizing the siRNA in a vector composed of cationic lipids or polymers, or to chemically modify it by conjugation to a molecule. This has enabled the first clinical developments of siRNAs to begin very quickly after their discovery, for the treatment of various acquired or hereditary pathologies. In 2018, the first siRNA-containing drug was approved by the FDA and the EMA for the treatment of an inherited metabolic disease, the hereditary transthyretin amyloidosis. In this review, we discuss the different barriers to the siRNA after systemic administration and how vectorization or chemical modifications lead to avoid it. We describe some interesting clinical developments and finally, we present the future perspectives. Clinical intraportal pancreatic islet infusion is popular for treating type I diabetes. However, multiple doses of islets and anti-rejection protocols are needed to compensate for early large cell losses post-infusion due to the harsh hepatic environment. Thus, extrahepatic sites are utilized to enable efficient islet engraftment and reduce islet mass. Here, we reported an effective islet revascularization protocol that was based on the co-implantation of islet/fibrin gel construct with poly(lactic-co-glycolic) acid sheet releasing NECA (5′-(N-ethylcarboxamido) adenosine; a potent agonist of adenosine) into mouse epididymal fat pad. Thin, flexible sheets (d = 4 mm) prepared by simple casting exhibited sustained NECA release for up to 21 days, which effectively improved early islet engraftment with a median diabetic reversal time of 18.5 days. Western blotting revealed the facilitative effect of NECA on VEGF expression from islets in vitro and from grafts in vivo. In addition, NECA directly promoted the angiogenic activities of islet-derived endothelial cells by enhancing their proliferation and vessel-like tube formation. As a result, neovasculatures were effectively formed in the engrafted islet vicinity, as evidenced by vasculature imaging and immunofluorescence. Taken together, we suggest NECA-releasing PLGA sheets offer a safe and effective drug delivery system that enhances islet engraftment while reducing islet mass at extrahepatic sites for clinical relevance. High transplant cell loss is a major barrier to translation of stem cell therapy for pathologies of the brain and spinal cord. Encapsulated delivery of stem cells in biomaterials for cell therapy is gaining popularity but experimental research has overwhelmingly used laboratory grade materials unsuitable for human clinical use – representing a further barrier to clinical translation. A potential solution is to use neurosurgical grade materials routinely used in clinical protocols which have an established human safety profile. Here, we tested the ability of Duragen Plus™ – a clinical biomaterial used widely in neurosurgical duraplasty procedures, to support the growth and differentiation of neural stem cells- a major transplant population being tested in clinical trials for neurological pathology. Genetic engineering of stem cells yields augmented therapeutic cells, so we further tested the ability of the Duragen Plus™ matrix to support stem cells engineered using magnetofection technology and minicircle DNA vectors- a promising cell engineering approach we previously reported (Journal of Controlled Release, 2016 a &b). The safety of the nano-engineering approach was analysed for the first time using sophisticated data-independent analysis by mass spectrometry-based proteomics. We prove that the Duragen Plus™ matrix is a promising biomaterial for delivery of stem cell transplant populations, with no adverse effects on key regenerative parameters. This advanced cellular construct based on a combinatorial nano-engineering and biomaterial encapsulation approach, could therefore offer key advantages for clinical translation.