Mobilization-based chemotherapy-free engraftment of gene-edited human hematopoietic stem cells.

Hematopoietic stem/progenitor cell gene therapy (HSPC-GT) is proving successful to treat several genetic diseases. HSPCs are mobilized, harvested, genetically corrected ex vivo, and infused, after the administration of toxic myeloablative conditioning to deplete the bone marrow (BM) for the modified cells. We show that mobilizers create an opportunity for seamless engraftment of exogenous cells, which effectively outcompete those mobilized, to repopulate the depleted BM. The competitive advantage results from the rescue during ex vivo culture of a detrimental impact of mobilization on HSPCs and can be further enhanced by the transient overexpression of engraftment effectors exploiting optimized mRNA-based delivery. We show the therapeutic efficacy in a mouse model of hyper IgM syndrome and further developed it in human hematochimeric mice, showing its applicability and versatility when coupled with gene transfer and editing strategies. Overall, our findings provide a potentially valuable strategy paving the way to broader and safer use of HSPC-GT.

Electrochemical-Conditioning-Free and Water-Resistant Hybrid AlCl3 /MgCl2 /Mg(TFSI)2 Electrolytes for Rechargeable Magnesium Batteries.

Rechargeable magnesium batteries are a promising alternative to Li-based energy storage because of their abundant and inexpensive components. The high sensitivity and reactivity of the organic Mg2+ electrolyte makes their development challenging. Herein, we develop a new hybrid electrolyte, based on three simple inorganic salts of MgCl2 , AlCl3 , and Mg(TFSI)2 . The electrolyte exhibits unprecedented electrochemical performance for reversible deposition and stripping of Mg, with Coulombic efficiency up to 97 %, overpotential down to 0.10 V, good stability especially for aluminum and stainless-steel current collectors. It maintained its activity even after introducing 2000 ppm water and it could be prepared from impure chemicals. A full cell with the hybrid electrolyte and Mg foil as anode, Mo6 S8 as cathode gave a specific capacity of 98 mAh g-1 and maintained 94 % capacity after 100 cycles at a rate of 0.20 C, indicating the good compatibility of the hybrid electrolyte.

Calibration-free and ready-to-use wearable electroanalytical reporting system (r-WEAR) for long-term remote monitoring of electrolytes markers.

A major bottleneck in the development of wearable ion-selective sensors is the inherent conditioning and calibration procedures at the user's end due to the signal's instability and non-uniformity. To address this challenge, we developed a strategy that integrates three interdependent materials and device engineering approaches to realize a Ready-to-use Wearable ElectroAnalytical Reporting system (r-WEAR) for reliable electrolytes monitoring. The strategy collectively utilized (1) finely-configured diffusion-limiting polymers to stabilize the electromotive force in the electrodes, (2) a uniform electrical induction in electrochemical cells to normalize the open-circuit potential (OCP), and (3) an electrical shunt to maintain the OCP across the entire sensor in the r-WEAR. The approaches jointly enable fabrication of homogeneously stable and uniform ion-selective sensors, eliminating common conditioning and calibration practices. As a result, the r-WEAR demonstrated a signal's variation down to ±1.99 mV with a signal drift of 0.5 % per hour (0.12 mV h-1) during a 12-h continuous measurement of 10 sensors and a signal drift as low as 13.3 µV h-1 during storage. On-body evaluations of the r-WEAR for four days without conditioning and re-/calibration further validated the sensor's performance in realistic settings, indicating its remarkable potential for practical usage in a user operation-free manner in wearable healthcare applications.

Activating Magnesium Electrolytes through Chemical Generation of Free Chloride and Removal of Trace Water.

Mg batteries are attractive next-generation energy storage systems due to their high natural abundance, inexpensive cost, and high theoretical capacity compared to conventional Li-ion based systems. The high energy density is achieved by electrodeposition and stripping of a Mg metal anode and requires the development of effective electrolytes enabled by a mechanistic understanding of the charge-transfer mechanism. The magnesium aluminum chloride complex (MACC) electrolyte is a good model system to study the mechanism as the solution phase speciation is known. Previously, we reported that minor addition of Mg(HMDS)2 to the MACC electrolyte causes significant improvement in the Mg deposition and stripping voltammetry resulting in good Coulombic efficiency on cycle one and, therefore, negating the need for electrochemical conditioning. To determine the cause of the improved electrochemistry, here we probe the speciation of the electrolyte after Mg(HMDS)2 addition using Raman spectroscopy, 27Al nuclear magnetic resonance spectroscopy, and 1H-29Si heteronuclear multiple bond correlation spectroscopy on MACC + Mg(HMDS)2 at various Mg(HMDS)2 concentrations. Mg(HMDS)2 scavenges trace H2O, but it also reacts with MACC complexes, namely, AlCl4-, to form free Cl-. We suggest that although both the removal of H2O and the formation of free Cl- improve electrochemistry by altering the speciation at the interface, the latter has a profound effect on electrodeposition and stripping of Mg.

Surface Engineering of a Mg Electrode via a New Additive to Reduce Overpotential.

In nonaqueous Mg batteries, inactive adsorbed species and the passivation layer formed from the reactive Mg with impurities in the electrolyte seriously affect the Mg metal/electrolyte interface. These adlayers can impede the passage of Mg2+ ions, leading to a high Mg plating/stripping overpotential. Herein, we report the properties of a new additive, bismuth triflate (Bi(OTf)3), for synthesizing a chlorine-free Mg electrolyte to enhance Mg plating/stripping from initial cycles. The beneficial effect of Bi(OTf)3 can be ascribed to Bi/Mg3Bi2 formed in situ on the Mg metal surface, which increases the charge transfer during the on-off transition by reducing the adsorption of inactive species on the Mg surface and enhancing the resistance of the reactive surface to passivation. This simple method provides a new avenue to improve the compatibility between the Cl-free Mg electrolyte and the Mg metal anode.

Conditioning-Free Mg Electrolyte by the Minor Addition of Mg(HMDS)2.

Mg-based batteries are an attractive next-generation energy storage chemistry due to the high natural abundance and inexpensive cost of Mg, along with the high theoretical energy density compared to that of conventional Li-ion chemistry. The greater energy density is predicated on a Mg metal anode, and pathways to achieving reversible Mg electrodeposition and stripping are reliant on the development of Mg electrolytes. Although Mg electrolyte chemistry has advanced significantly from the reactive Grignards of the 1920s to the carboranes of this decade, there remains significant challenges in correlating the Mg metal anode electrochemistry with the composition of the electrolyte salts as a result of the complicated interface of Mg metal and the electrolyte. To probe the effect of the interface on Mg electrodeposition, we turn to an electrolyte with a known solution-phase composition: the magnesium aluminum chloride complex (MACC) electrolyte. The MACC electrolyte requires electrolytic conditioning to support reversible Mg electrodeposition and stripping. Here, we show that a small concentration (2-5 mM) of Mg(HMDS)2 with respect to the MACC electrolyte salts suppresses Al3+ deposition and promotes reversible Mg electrodeposition and stripping in the first cycle. The significant effect of a small concentration of additive is attributed to changes to the electrode interface. The impact of the Mg interface on the observed electrochemical performance is discussed.