Adeno-associated virus vectors for human gene therapy

Adeno-associated virus(AAV) is a small,non-enveloped virus that contains a single-stranded DNA genome. It was the first gene therapy drug approved in the Western world in November 2012 to treat patients with lipoprotein lipase deficiency. AAV made history and put human gene therapy in the forefront again. More than four decades of research on AAV vector biology and human gene therapy has generated a huge amount of valuable information. Over 100 AAV serotypes and variants have been isolated and at least partially characterized. A number of them have been used for preclinical studies in a variety of animal models. Several AAV vector production platforms,especially the baculovirus-based system have been established for commercial-scale AAV vector production. AAV purification technologies such as density gradient centrifugation,column chromatography,or a combination,have been well developed. More than 117 clinical trials have been conducted with AAV vectors. Although there are still challenges down the road,such as crossspecies variation in vector tissue tropism and gene transfer efficiency,pre-existing humoral immunity to AAV capsids and vector dose-dependent toxicity in patients,the gene therapy community is forging ahead with cautious optimism. In this review I will focus on the properties and applications of commonly used AAV serotypes and variants,and the technologies for AAV vector production and purification. I will also discuss the advancement of several promising gene therapy clinical trials.

A coupled electrochemical system for CO_(2)capture,conversion and product purification

The efficient utilization of carbon dioxide(CO_(2))as a resource,comprises three key processes:CO_(2)capture,catalytic conversion and product purification.Using the renewable electricity to drive these processes provides a promising pathway for mitigating the ever-increasing atmospheric CO_(2)concentration whilst simultaneously addressing the growing energy demand.Although each of the three individual processes has been extensively investigated during the past decade,the rapid and economically viable reduction of CO_(2)emissions still calls for the development of an integrated electrochemical system driven by the renewable electricity to achieve carbon neutrality.Herein,we report a systematic protocol to bridge the three individual CO_(2)utilization processes into one coupled electrochemical system:a bipolar membrane electrodialysis(BPMED)cell generating alkaline and acidic solutions for the capture and recovery of CO_(2),a flow cell with an Ag gas diffusion electrode(GDE)for the selective electrocatalytic reduction of the recovered CO_(2),and an alkaline solution container for the purification of the gaseous products and recycle of the unreacted CO_(2).Consequently,the coupled electrochemical system successfully captured CO_(2)from the simulated flue gas and converted it into a pure syngas stream.