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Intervención de Mathieu Bernard (Université de Lausanne) en la mesa redonda "El impacto del agradecimiento y la cultura".

Gene delivery vectors based on adeno-associated virus (AAV) are highly promising due to several desirable features of this parent virus, including a lack of pathogenicity, efficient infection of dividing and non-dividing cells and sustained maintenance of the viral genome. However, the conclusion from clinical data using these vectors is that there is a need to develop new AAVs with a higher transduction efficiency and specificity for relevant target tissues. To overcome these limitations, we chemically modified the surface of the capsid of AAV vectors. These modifications were achieved by chemical coupling of a ligand by the formation of a thiourea functionality between the amino group of the capsid proteins and the reactive isothiocyanate motif incorporated into the ligand. This strategy does not require genetic engineering of the capsid sequence. The proof of concept was first evidenced using a fluorophore (FITC). Next, we coupled the N-acetylgalactosamine ligand onto the surface of the AAV capsid for asialoglycoprotein receptor-mediated hepatocyte-targeted delivery. Chemically-modified capsids also showed reduced interactions with neutralizing antibodies. Taken together, our findings reveal the possibility of creating a specific engineered platform for targeting AAVs via chemical coupling.

When suspended particles are pushed by liquid flow through a constricted channel, they might either pass the bottleneck without trouble or encounter a permanent clog that will stop them forever. However, they may also flow intermittently with great sensitivity to the neck-to-particle size ratio D / d . In this Rapid Communication, we experimentally explore the limits of the intermittent regime for a dense suspension through a single bottleneck as a function of this parameter. To this end, we make use of high time- and space-resolution experiments to obtain the distributions of arrest times ( T ) between successive bursts, which display power-law tails ( ∝ T − α ) with characteristic exponents. These exponents compare well with the ones found for as disparate situations as the evacuation of pedestrians from a room, the entry of a flock of sheep into a shed, or the discharge of particles from a silo. Nevertheless, the intrinsic properties of our system (i.e., channel geometry, driving and interaction forces, particle size distribution) seem to introduce a sharp transition from a clogged state ( α ≤ 2 ) to a continuous flow, where clogs do not develop at all. This contrasts with the results obtained in other systems where intermittent flow, with power-law exponents above two, were obtained.