No abstract

Whereas aptamers have shown to bind to targets with similar affinities and specificities to those of antibodies, aptamers have several advantages that could outweigh antibody technology and open new opportunities for better medical and diagnostic solutions. However, the current status of the aptamer technology suffers from several technical limitations that slowdown the progression of novel aptamers into the clinic and makes the business around aptamers challenging.

Aggregation of type 1 Fc 4 receptors (Fc 4 RI) on mast cells activates a biochemical cascade that culminates in secretion of inflammatory mediators, as well as in changes of cell morphology and adhesion properties. Some of the intracellular components involved in the early coupling events are still unidentified. Here we show that two adaptor proteins, downstream of tyrosine kinases (Dok)-1 and Dok-2, are involved in the Fc 4 RI coupling cascade in the rat mucosal-type mast cells of the RBL-2H3 line. Dok-1 is found to be constitutively associated with the Fc 4 RI, even in untreated cells, and this interaction is not affected by this receptor's aggregation. Both Dok forms undergo a fast and relatively long-term tyrosylphosphorylation. This modification of Dok-1 increases its association with RasGAP, suggesting that it is modulating Ras activity. Indeed, we further found that Fc 4 RI-mediated Ras/ Raf1/Erk signaling as well as the de novo synthesis of TNF- § are markedly reduced in cells overexpressing Dok-1. Moreover, Fc 4 RI clustering causes both Dok-1 and Dok-2 to become docking sites for other signaling molecules including Nck, CrkL and Cas. The latter proteins have been implicated particularly in regulation of the actin-cytoskeletal reorganization. Hence Dok-1/Dok-2 may also be involved in the Fc 4 RI-stimulated processes of cytoskeleton rearrangement required for cell adhesion, membrane ruffling and exocytosis.

In recent years, reagentless aptamer biosensors, named aptasensors, have shown significant advancements. Particularly, electrochemical aptasensors could change the field of biosensors in this era, where digitalization seems to be a common goal of many fields. Biomedical devices are integrating electronic technologies for detecting pathogens, biomolecules, small molecules, and ions, and the physical-chemical properties of nucleic acid aptamers makes them very interesting for these devices. Aptamers can be easily synthesized and functionalized with functional groups for immobilization and with redox chemical groups that allow for the conversion of molecular interactions into electrical signals. Furthermore, non-labeled aptamers have also been utilized. This review presents the current challenges involved in aptasensor architectures based on gold electrodes as transducers.