PABPN1 gene therapy for oculopharyngeal muscular dystrophy

International audienceOculopharyngeal muscular dystrophy (OPMD) is an autosomal dominant, late-onset muscle disorder characterized by ptosis, swallowing difficulties, proximal limb weakness and nuclear aggregates in skeletal muscles. OPMD is caused by a trinucleotide repeat expansion in the PABPN1 gene that results in an N-terminal expanded polyalanine tract in polyA-binding protein nuclear 1 (PABPN1). Here we show that the treatment of a mouse model of OPMD with an adeno-associated virus-based gene therapy combining complete knockdown of endogenous PABPN1 and its replacement by a wild-type PABPN1 substantially reduces the amount of insoluble aggregates, decreases muscle fibrosis, reverts muscle strength to the level of healthy muscles and normalizes the muscle transcriptome. The efficacy of the combined treatment is further confirmed in cells derived from OPMD patients. These results pave the way towards a gene replacement approach for OPMD treatment

BioCloneBot: A versatile, low-cost, and open-source automated liquid handler

Liquid handler systems can provide significant benefits to researchers by automating laboratory work, however, their unaffordable price provides a steep barrier to entry. Therefore, we provide the BioCloneBot, a versatile, low-cost, and open-source automated liquid handler. This system can be easily built with 3D-printed parts and readily available commercial components. The BioCloneBot is highly adaptive to user needs and facilitates various liquid handling tasks in research and diagnostics. Its user-friendly interface and programmable nature make it suitable for a wide range of applications, from small-scale experiments to larger laboratory setups. By utilizing BioCloneBot, researchers and scientists can streamline their liquid handling processes without the financial constraints posed by traditional systems. In this paper, we detail the design, construction, and validation of BioCloneBot, showcasing its precise control, accuracy, and repeatability in various liquid handling tasks. The open-source nature of the system encourages collaboration and customization, enabling researchers to contribute and adapt the technology to specific experimental requirements