Human iPSC-derived neural stem cells engraft and improve pathophysiology of MPS I mice.

Mucopolysaccharidosis type I (MPS I) is a metabolic disorder characterized by a deficiency in α-l-iduronidase (IDUA), leading to impaired glycosaminoglycan degradation. Current approved treatments seek to restore IDUA levels via enzyme replacement therapy (ERT) and/or hematopoietic stem cell transplantation (HSCT). The effectiveness of these treatment strategies in preventing neurodegeneration is limited due to the inability of ERT to penetrate the blood-brain barrier (BBB) and HSCT's limited CNS reconstitution of IDUA levels.

Three-Dimensional Laser Creation of a Near-IR Laser-Gain Medium Based on Hydride Donor/Acceptor Complexes Made of Coupled Laser-Induced Silver Nanoclusters with Ytterbium Ions.

Femtosecond laser inscription in a ytterbium-doped silver-containing phosphate glass is demonstrated by achieving 3D highly localized laser-induced silver photochemistry. The produced fluorescent silver nanoclusters lead to high optical contrast in the visible range, showing that the coinsertion of Yb ions is not detrimental to the silver-based photochemistry. We demonstrate efficient energy transfer from these silver nanoclusters to the rare-earth Yb ions, leading to near-IR background-free fluorescence emission.

Base editing of the GLB1 gene is therapeutic in GM1 gangliosidosis patient-derived cells.

GM1 gangliosidosis is an autosomal recessive neurodegenerative lysosomal storage disease caused by pathogenic variants in the GLB1 gene, limiting the production of active lysosomal β-galactosidase. Phenotypic heterogeneity is due in part to variant type, location within GLB1, and the amount of residual enzyme activity; in the most severe form, death occurs in infancy. With no FDA approved therapeutics, development of efficacious strategies for the disease is pivotal.

Base editing rescues acid α-glucosidase function in infantile-onset Pompe disease patient-derived cells.

Infantile-onset Pompe disease (IOPD) results from pathogenic variants in the gene, which encodes acid α-glucosidase. The correction of pathogenic variants through genome editing may be a valuable one-time therapy for PD and improve upon the current standard of care. We performed adenine base editing in human dermal fibroblasts harboring three transition nonsense variants, c.