Volume 31

Cover Credit: The reframed pendrin protein expressed in the endolymphatic sac of a CRISPR/Cas9- mediated exon-skipping animal model SLC26A4 c.919-2 A>G is a splice-site variant leading to hereditary hearing loss (DFNB4), which is particularly common among East Asians. Exon-skipping techniques have shown promise in correcting diseases caused by open-reading frame mutations, suggesting their potential application in the SLC26A4 c.919-2 A>G gene therapy. Using a CRISPR/Cas9 exon-skipping strategy, researchers generated a mouse model with reframed pendrin, designated as Slc26a4∆E8+E9/∆E8+E9. Confocal imaging reveals that reframed pendrin (indicated in green) is expressed in the membrane and cytosol of endolymphatic sac epithelial cells in the Slc26a4∆E8+E9/∆E8+E9 mice, whereas pendrin is absent in the Slc26a4 c.919-2 A>G mice.

Cover Credit: The systemic delivery of a novel BBB-penetrant capsid variant coding for GFP (AAV9-P31-GFP) in mice resulted in a widespread CNS transduction. At the level of the cerebellar cortex, Purkinje neurons were randomly transduced, most often showing a Golgi-like stain with a precise definition of the cell soma and the full dendritic arborization.

Cover Credit: Alfred Pasieka/Science Photo Library

Cover Credit: Brain cortical slices from intracerebroventricular (ICV)-injected Neu1 -/- mice were subjected to immunofluorescence staining for NEU1 (red), Iba1 (green), and DAPI (blue). Expression of NEU1 was restored, including in the perikaryon of microglia (arrows). The morphology of microglia was also normalized.

Cover Credit: AAV-mediated gene therapy for hereditary hearing loss is transitioning from basic research to clinical application. The biodistribution of different AAV vectors after inner ear injection is crucial for researchers to select appropriate serotypes with targeted capabilities while decreasing non-target expression. The image shows the brain transduction of AAV1, AAV2, Anc80L65, AAV9, AAV-PHP.B, and AAV-PHP.eB after round window membrane (RWM) delivery at neonatal mice.

Cover Credit: Alfred Pasieka/Science Photo Library