Nanobody against SARS-CoV-2 non-structural protein Nsp9 inhibits viral replication in human airway epithelia.

Nanobodies are emerging as critical tools for drug design. Several have been recently created to serve as inhibitors of severe acute respiratory syndrome coronavirus s (SARS-CoV-2) entry in the host cell by targeting surface-exposed spike protein. Here we have established a pipeline that instead targets highly conserved viral proteins made only after viral entry into the host cell when the SARS-CoV-2 RNA-based genome is translated.

Near-Infrared Light Activated Formulation for the Spatially Controlled Release of CRISPR-Cas9 Ribonucleoprotein for Brain Gene Editing.

The CRISPR/Cas9 system has emerged as a promising platform for gene editing; however, the lack of an efficient and safe delivery system to introduce it into cells continues to hinder clinical translation. Here, we report a rationally designed gene-editing nanoparticle (NP) formulation for brain applications: an sgRNA:Cas9 ribonucleoprotein complex is immobilized on the NP surface by oligonucleotides that are complementary to the sgRNA. Irradiation of the formulation with a near-infrared (NIR) laser generates heat in the NP, leading to the release of the ribonucleoprotein complex.

Development of high-affinity fluorinated ligands for cannabinoid subtype 2 receptor, and in vitro evaluation of a radioactive tracer for imaging.

The development of neurodegenerative diseases is associated with cerebral inflammation, which activates resident immune cells of the central nervous system (CNS), namely microglial cells that show an up-regulation of the cannabinoid subtype 2 receptor (CBR) expression. Therefore our work aimed to design and synthesize a radiotracer for the detection of CBR expression by positron emission tomography (PET) allowing an early diagnosis of neurodegenerative diseases. For the development of such a PET tracer, N-alkyl-substituted indole-3-yl-tetramethylcyclopropylketones served as lead structures due to their high CBR potency and selectivity, allowing radiolabeling on the N-alkyl chain.

Innate Immune Pathways Promote Oligodendrocyte Progenitor Cell Recruitment to the Injury Site in Adult Zebrafish Brain.

The oligodendrocyte progenitors (OPCs) are at the front of the glial reaction to the traumatic brain injury. However, regulatory pathways steering the OPC reaction as well as the role of reactive OPCs remain largely unknown. Here, we compared a long-lasting, exacerbated reaction of OPCs to the adult zebrafish brain injury with a timely restricted OPC activation to identify the specific molecular mechanisms regulating OPC reactivity and their contribution to regeneration.