Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Background: Mucopolysaccharidosis IIIC (MPSIIIC) is one of four Sanfilippo diseases sharing clinical symptoms of severe cognitive decline and shortened lifespan. The missing enzyme, heparan sulfate acetyl-CoA: α-glucosaminide-N-acetyltransferase (HGSNAT), is bound to the lysosomal membrane, therefore cannot cross the blood-brain barrier or diffuse between cells. We previously demonstrated disease correction in MPSIIIC mice using an Adeno-Associated Vector (AAV) delivering HGSNAT via intraparenchymal brain injections using an AAV2 derived AAV-truetype (AAV-TT) serotype with improved distribution over AAV9.
Methods: Here, intraparenchymal AAV was delivered in sheep using catheters or Hamilton syringes, placed using Brainlab cranial navigation for convection enhanced delivery, to reduce proximal vector expression and improve spread.
Results: Hamilton syringes gave improved AAV-GFP distribution, despite lower vector doses and titres. AAV-TT-GFP displayed moderately better transduction compared to AAV9-GFP but both serotypes almost exclusively transduced neurons. Functional HGSNAT enzyme was detected in 24-37% of a 140g gyrencephalic sheep brain using AAV9-HGSNAT with three injections in one hemisphere.
Conclusions: Despite variabilities in volume and titre, catheter design may be critical for efficient brain delivery. These data help inform a clinical trial for MPSIIIC.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10320977 | PMC |
| http://dx.doi.org/10.1186/s12967-023-04208-1 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Morphology of Taylor Cone in Stable Regime: Experimental and Numerical Insights.
Langmuir
September 2025
School of Energy and Power Engineering, Jiangsu University, Zhenjiang, Jiangsu 212013, China.
In the stable cone-jet regime, liquid usually presents the shape of a cone extended by a jet at its apex, with jet breakup yielding fine drops. The dynamics of the Taylor cone critically affect the stability of the jet and further determine the jet and/or drop size. In the present work, the morphology of the Taylor cone, cone length, and cone angle were studied through experimental and numerical means, where the operating parameters and liquid properties are considered.
View Article and Find Full Text PDFQuantifying the Reduction of OER Overpotential on Magnetic Electrocatalysts Under Magnetic Fields.
Small Methods
September 2025
School of Physics and Optoelectronics, South China University of Technology, Wushan Road 381, Guangzhou, 510640, China.
Magnetic-field enhancement of the oxygen evolution reaction (OER) represents a promising route toward more efficient alkaline water electrolyzers, yet its origin remains debated due to overlapping effects of mass transport and reaction kinetics. Here, we present a general experimental strategy that employs strong forced convection to suppress uncontrolled transport arising from natural diffusion and magnetohydrodynamic (MHD) flows. Using polycrystalline Au electrodes, we show that this approach resolves subtle OER variations under controlled flow and field conditions.
View Article and Find Full Text PDFComputational Fluid Dynamic Model Prediction of Enhanced Glymphatic Clearance in Response to Focused Ultrasound-Mediated Blood-Brain Barrier Opening.
Adv Sci (Weinh)
September 2025
Department of Biomedical Engineering, University of Virginia, Charlottesville, VA, 22908, USA.
Focused Ultrasound (FUS) is the concentration of acoustic energy into a small region to produce therapeutic bioeffects. FUS-induced blood-brain barrier opening (BBBO), a strategy to deliver drugs and genes to the brain, also enhances glymphatic drainage, the brain-specific waste clearance system. Thus, FUS BBBO is a promising strategy for addressing the accumulation of neurotoxic solutes that are characteristic of many neurodegenerative diseases.
View Article and Find Full Text PDFA Non-Newtonian Sol Electrolyte with Shear-Thinning Effect for Stable Zn Metal Anodes.
Small
September 2025
Hefei National Research Center for Physical Sciences at the Microscale, Department of Materials Science and Engineering, University of Science and Technology of China, Hefei, 230026, China.
Aqueous Zn metal batteries (AZMBs) emerge as promising candidates for large-scale energy storage due to their cost-effectiveness and safety, yet challenges like dendrite growth, hydrogen evolution, and poor cycling stability persist. Herein, a homogeneous non-Newtonian electrolyte (NNE) with shear-thinning property is designed to address these challenges. The NNE is prepared by incorporating a thickening polyquaternary ammonium salt, forming a super-viscous sol electrolyte while maintaining high ionic conductivity (52.
View Article and Find Full Text PDFConnexin hemichannel blockade by abEC1.1 disrupts glioblastoma progression, suppresses invasiveness, and reduces hyperexcitability in preclinical models.
Cell Commun Signal
September 2025
CNR Institute of Biochemistry and Cell Biology, Monterotondo, Rome, 00015, Italy.
Background: Connexin (Cx) hemichannels (HCs) contribute to glioblastoma (GBM) progression by facilitating intercellular communication and releasing pro-tumorigenic molecules, including ATP and glutamate.
Methods: The efficacy of abEC1.1, a monoclonal antibody that inhibits Cx26, Cx30, and Cx32 HCs, was assessed in vitro by measuring invasion capability, dye and Ca uptake, glutamate and ATP release in patient-derived GBM cultures or organoids.