In vitro and in vivo targeted delivery of IL-10 interfering RNA by JC virus-like particles

<p>Abstract</p> <p>Background</p> <p>RNA interference (RNAi) is a powerful tool to silence gene expression post-transcriptionally. Delivering sequences of RNAi <it>in vivo </it>remains a problem. The aim of this study was to use JC virus (JCV) virus-like particles (VLPs) as a vector for delivering RNAi in silencing the cytokine gene of IL-10.</p> <p>Methods</p> <p>JCV VLPs were generated by recombinant JCV VP1 protein in yeast expression system. DNA fragment containing IL-10 shRNA was packaged into VLPs by osmotic shock.</p> <p>Results</p> <p>In RAW 264.7 cells, IL-10 shRNA was found to reduce IL-10 expression by 85 to 89%, as compared with VLPs alone. IL-10 shRNA did not cross-react with TNF-alpha mRNA or influence the expression of TNF-alpha. In BALB/c mice IL-10 shRNA could reduce 95% of IL-10 secretion. Surprisingly, it also down regulated TNF-alpha expression.</p> <p>Conclusions</p> <p>We show for the first time that JCV VLPs empty capsids are competent vectors to deliver RNAi and are nontoxic to cells, suggesting that JCV VLPs is an efficient agent to deliver RNAi in both murine macrophage cells and BALB/c mice. This system provides an efficient means for delivering the RNAi for gene therapy purposes.</p

Disseminated candidemia refractory to caspofungin therapy in an infant with extremely low birth weight

Systemic fungal infections have high morbidity and mortality rates in neonates, especially neonates with an extremely low birth weight (ELBW). Here, we describe a 21-day-old ELBW female infant with an amphotericin B-unresponsive congenital Candida albicans infection that was treated with caspofungin. Blood sterilization was performed during the first episode, but a second episode of candidemia occurred after the discontinuation of caspofungin. Blood sterilization was again performed during the second round of caspofungin treatment, but fungal endocarditis and renal fungal balls still developed during the second episode. Caspofungin can be considered for invasive candidiasis in premature infants, especially in life-threatening situations. As for the focal lesions, more aggressive treatments other than just parenteral antibiotics should be considered. The literature regarding caspofungin therapy for neonatal candidiasis is also reviewed

Erratum to: Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition) (Autophagy, 12, 1, 1-222, 10.1080/15548627.2015.1100356

non present