Single-swap editing for the correction of common Duchenne muscular dystrophy mutations

Duchenne muscular dystrophy (DMD) is a fatal X-linked recessive disease of progressive muscle weakness and wasting caused by the absence of dystrophin protein. Current gene therapy approaches using antisense oligonucleotides require lifelong dosing and have limited efficacy in restoring dystrophin production. A gene editing approach could permanently correct the genome and restore dystrophin protein expression. Here, we describe single-swap editing, in which an adenine base editor edits a single base pair at a splice donor site or splice acceptor site to enable exon skipping or reframing. In human induced pluripotent stem cell-derived cardiomyocytes, we demonstrate that single-swap editing can enable beneficial exon skipping or reframing for the three most therapeutically relevant exons—DMD exons 45, 51, and 53—which could be beneficial for 30% of all DMD patients. Furthermore, an adeno-associated virus delivery method for base editing components can efficiently restore dystrophin production locally and systemically in skeletal and cardiac muscles of a DMD mouse model containing a deletion of Dmd exon 44. Our studies demonstrate single-swap editing as a potential gene editing therapy for common DMD mutations

Glycerol-based deep eutectic solvents: Physical properties

Deep eutectic solvents (DESs) have been used in many industrial applications. DES is a mixture of a salt and a hydrogen bond donor (HBD). In this study, 70 DESs were synthesized successfully based on glycerol (Gly) as the HBD with different phosphonium and ammonium salts, namely methyl triphenyl phosphonium bromide (MTPB), benzyl triphenyl phosphonium chloride (BTPC), allyl triphenyl phosphonium bromide (ATPB), choline chloride (ChCl), N,N-diethylethanolammonium chloride (DAC), and tetra-n-butylammonium bromide (TBAB). The DESs were prepared using different molar ratios of the HBD to the salts. The freezing point of each DES was determined using Differential Scanning Calorimetry (DSC). The physical properties of these DESs, including density, viscosity, conductivity, and surface tension, were investigated as functions of temperature. In addition, the functional groups were analyzed utilizing Fourier transform infrared (FTIR) spectroscopy. It is worth noting that these systems have a wide variety of physical properties, which implies that these DESs would be suitable for diverse applications