Accelerated Endosomal Escape of Splice-Switching Oligonucleotides Enables Efficient Hepatic Splice Correction.

Splice-switching oligonucleotides (SSOs) can restore protein functionality in pathologies and are promising tools for manipulating the RNA-splicing machinery. Delivery vectors can considerably improve SSO functionality in vivo and allow dose reduction, thereby addressing the challenges of RNA-targeted therapeutics. Here, we report a biocompatible SSO nanocarrier, based on redox-responsive disulfide cross-linked low-molecular-weight linear polyethylenimine (cLPEI), for overcoming multiple biological barriers from subcellular compartments to en-route serum stability and finally in vivo delivery challenges.

Why do patients with antiphospholipid syndrome bleed? A clinical paradox.

Although worldwide-known criteria of antiphospholipid syndrome include thrombotic and obstetric events, a moderate number of patients manifest with bleeding episodes during course of the disease, which is typically attributed to the long-term anticoagulation. However, these haemorrhagic manifestations sometimes are part of pathophysiological changes that might occur secondary to the disease that involves endothelial activation, platelets dysfunction and blood clot factors misfunction. Recognizing these mechanisms of bleeding is crucial not only due to the need of treatment change or adding, but also because of changes in the disease' prognosis.