No abstract

Nerve guide conduits (NGCs) with geometric design have shown significant advantages in guidance of nerve reinnervation across the defect of injured peripheral nerves. It is realized that intraluminal fillers with distinctive structure can effectively provide an inner guidance for sprouting of axons and improve the permeability of NGC. In this work, a poly(lactic‐co‐glycolic acid) (PLGA) NGC is prepared containing intraluminal sponge fillers (labeled as ISF‐NGC) and used for reconstruction of a rat sciatic nerve with a 10 mm gap. For comparison, the same procedure is applied to a single hollow PLGA NGC (labeled as H‐NGC) and an autologous nerve. As evidenced by significantly improved nerve morphology and function, the ISF‐NGC achieves a superior nerve repair effect over H‐NGC, which is comparable to autologous nerve grafting. It is likely that the H‐NGC only provides a protected tunnel for nerve fiber regrowth and axonal extension, while ISF‐NGC offers an extracellular matrix‐mimetic architecture as autograft to provide contact guidance for nerve reinnervation. This newly developed ISF‐NGC is a promising candidate to aid nerve reinnervation across longer gaps commonly encountered in clinical cases.

Our rapidly dissolving MNs patch appears to an excellent, painless alternative to conventional SC injection of EXT, and this minimally invasive device might also be suitable for other biotherapeutics.

For efficient transgene delivery and expression, internalized nucleic acids should quickly escape from cellular endosomes and lysosomes to avoid enzymatic destruction and degradation. Here, we report a novel strategy for safe and efficient endosomal/lysosomal escape of transgenes mediated by Pluronic L64, a neutral amphiphilic triblock copolymer. L64 enhanced the permeability of biomembranes by structural disturbance and pore formation in a concentration- and time-dependent manner. When applied at optimal concentration, it rapidly reached the endosome/lysosome compartments, where it facilitated escape of the transfection complex from the compartments and dissociation of the complex. Therefore, when applied properly, L64 not only significantly increased polyethylenimine- and liposome-mediated transgene expression, but also decreased the cytotoxicity occasioned by transfection process. Our studies revealed the function and mechanism of neutral amphiphilic triblock copolymer as potent mediator for safe and efficient gene delivery.

Gene therapy has recently witnessed accelerated progress as a new therapeutic strategy with the potential to treat a range of inherited and acquired diseases. Billions of dollars have been invested in basic and clinical research on gene medicine, with ongoing clinical trials focused on cancer, monogenic diseases, cardiovascular diseases and other refractory diseases. Advances addressing the inherent challenges of gene therapy, particularly those related to retaining the delivery efficacy and minimizing unwanted immune responses, provide the basis for the widespread clinical application of gene medicine. Several types of genes delivered by viral or non‐viral delivery vectors have demonstrated encouraging results in both animals and humans. As augmented by clinical indications, gene medicine techniques have rapidly become a promising alternative to conventional therapeutic strategies because of their better clinical benefit and lower toxicities. Their application in the clinic has been extensive as a result of the approval of many gene therapy drugs in recent years. In this review, we provide a comprehensive overview of the clinical translation of gene medicine, focusing on the key events and latest progress made regarding clinical gene therapy products. We also discuss the gene types and non‐viral materials with respect to developing gene therapeutics in clinical trials.