Delivering enhanced efficiency in the synthesis of α-diazosulfoxides by exploiting the process control enabled in flow

Continuous-flow generation of α-diazosulfoxides results in a two- to three-fold increase in yields and decreased reaction times compared to standard batch synthesis methods. These high yielding reactions are enabled by flowing through a bed of polystyrene-supported base (PS-DBU or PS-NMe2) with highly controlled residence times. This engineered solution allows the α-diazosulfoxides to be rapidly synthesized while limiting exposure of the products to basic reaction conditions, which have been found to cause rapid decomposition. In addition to improved yields, this work has the added advantage of ease of processing, increased safety profile, and scale-up potential.

Genetic medicines for CF: hype versus reality

Since identification of the CFTR gene over 25 years ago, gene therapy for cystic fibrosis (CF) has been actively developed. More recently gene therapy has been joined by other forms of “genetic medicines” including mRNA delivery, as well as genome editing and mRNA repair-based strategies. Proof-of-concept that gene therapy can stabilize the progression of CF lung disease has recently been established in a Phase IIb trial. An early phase study to assess the safety and explore efficacy of CFTR mRNA repair is ongoing, while mRNA delivery and genome editing-based strategies are currently at the pre-clinical phase of development. This review has been written jointly by some of those involved in the various CF “genetic medicine” fields and will summarize the current state-of-the-art, as well as discuss future developments. Where applicable, it highlights common problems faced by each of the strategies, and also tries to highlight where a specific strategy may have an advantage on the pathway to clinical translation. We hope that this review will contribute to the ongoing discussion about the hype versus reality of genetic medicine-based treatment approaches in CF.