However, for most disorders of the central nervous system (CNS), challenges in translating gene therapy approaches to the clinic include delivery across the blood-brain barrier (BBB) 6, 7, and the control of transgene expression 8. These breakthroughs and the advancement of recombinant adeno-associated viruses (rAAVs) have renewed interest in gene therapy for neurological disorders 3 - 5. Recent successes in gene therapy clinical trials include improvements in the vision of patients with leber congenital amaurosis 1, and the first life-saving treatment of neurodegeneration in infants with spinal muscular atrophy 2. Future gene therapies for neurological disorders could benefit from using a GFAP promoter to regulate transgene expression in response to disease-induced astrocytic reactivity. In peripheral organs, GFP expression was particularly strong in the liver, irrespective of the promoter.Ĭonclusion: The GFAP promoter enhanced transgene expression in proximity of Aβ plaques in the brain of TgCRND8 mice, and it also resulted in significant expression in the liver. Adjacent to Aβ plaques where GFAP is upregulated, the volume, surface area, and fluorescence intensity of the transgene GFP were greater in rAAV1/2-GFAP-GFP compared to rAAV1/2-HBA-GFP treated animals. Results: MRIgFUS targeting the cortex and hippocampus facilitated the entry of rAAV1/2 and GFP expression under the GFAP promoter was localized to GFAP-positive astrocytes. rAAV1/2 expression of the reporter green fluorescent protein (GFP) under a GFAP promoter was compared to GFP expression driven by the constitutive human beta actin (HBA) promoter. Methods: The delivery of intravenously injected recombinant adeno-associated virus mosaic serotype 1/2 (rAAV1/2) to the cortex and hippocampus of TgCRND8 mice was facilitated using transcranial MRI-guided focused ultrasound in combination with microbubbles (MRIgFUS), which transiently and locally increases the permeability of the blood-brain barrier (BBB). Here, we took advantage of the glial fibrillary acidic protein (GFAP) promoter to preferentially enhance transgene expression near plaques composed of amyloid-beta peptides (Aβ), a hallmark of Alzheimer's disease (AD), in the TgCRND8 mouse model of amyloidosis. It is a must-have tool for any researcher that conducts important experiments, generating complete projects that include more than simple graphs.Gene therapy can be designed to efficiently counter pathological features characteristic of neurodegenerative disorders. It runs detailed, thorough analysis and then enables you to check the resulting data for errors by retracing each performed step. GraphPad Prism bundles all the tools that you would expect from an application of its type. One of its most important advantages is that it uses a totally understandable language, avoiding statistical vocabulary. It is capable of automatically interpolating unknown values, performing statistical tests (F, T and ANOVA) to compare fits or test residuals for normality and much more. GraphPad Prism helps you perform non-linear regressions and significantly simplifies curve fitting, since it can fit multiple data sets with a single operation.ĭespite its easy approach, the application provides advanced analysis options. One cannot argue about its data organization capabilities, which is a rather important aspect, especially when it comes with scientific information. Its spreadsheet-like interface allows you to visualize the data in a structured manner, while providing quick access to all the tools you need. What makes GraphPad Prism worth your time is that it is not intended solely to statisticians, although having basic knowledge about the significance of the performed calculations is somewhat mandatory.
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While is is not intended to replace a professional statistics software, it can handle large data sets and allows you to perform various tests and measurements. The application bundles a wide array of features and tools designed to guide you through all the necessary steps of organizing the information and performing detailed statistical analysis. GraphPad Prism provides users with an full-featured, comprehensive biostatistics application that aims to assist biologists and researchers in analyzing complex sets of data and generating understandable graphs. A biostatistics and curve fitting application that can help biologists and researchers analyze large data sets and generate comprehensive statistics.
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