Artificial Rheotaxis

Motility is a basic feature of living microorganisms, and how it works is often determined by environmental cues. Recent efforts have focused on develop- ing artificial systems that can mimic microorganisms, and in particular their self-propulsion. Here, we report on the design and characterization of syn- thetic self-propelled particles that migrate upstream, known as positive rheo- taxis. This phenomenon results from a purely physical mechanism involving the interplay between the polarity of the particles and their alignment by a viscous torque. We show quantitative agreement between experimental data and a simple model of an overdamped Brownian pendulum. The model no- tably predicts the existence of a stagnation point in a diverging flow. We take advantage of this property to demonstrate that our active particles can sense and predictably organize in an imposed flow. Our colloidal system represents an important step towards the realization of biomimetic micro-systems withthe ability to sense and respond to environmental changesComment: Published in Science Advances [Open access journal of Science Magazine

Hepatic expression of GAA results in enhanced enzyme bioavailability in mice and non-human primates

International audiencePompe disease (PD) is a severe neuromuscular disorder caused by deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA). PD is currently treated with enzyme replacement therapy (ERT) with intravenous infusions of recombinant human GAA (rhGAA). Although the introduction of ERT represents a breakthrough in the management of PD, the approach suffers from several shortcomings. Here, we developed a mouse model of PD to compare the efficacy of hepatic gene transfer with adeno-associated virus (AAV) vectors expressing secretable GAA with long-term ERT. Liver expression of GAA results in enhanced pharmacokinetics and uptake of the enzyme in peripheral tissues compared to ERT. Combination of gene transfer with pharmacological chaperones boosts GAA bioavailability, resulting in improved rescue of the PD phenotype. Scale-up of hepatic gene transfer to non-human primates also successfully results in enzyme secretion in blood and uptake in key target tissues, supporting the ongoing clinical translation of the approach