Delivery of therapeutics to the central nervous system (CNS) is challenging due to the presence of the blood–brain barrier (BBB). Amongst various approaches that have been explored to facilitate drug delivery to the CNS, the use of cells that have the intrinsic ability to cross the BBB is relatively unexplored, yet very attractive. This paper presents a first proof‐of‐concept that demonstrates the feasibility of activated effector/memory CD4+ helper T cells (CD4+ TEM cells) as carriers for the delivery of polymer nanoparticles across the BBB. This study shows that CD4+ TEM cells can be decorated with poly(ethylene glycol)‐modified polystyrene nanoparticles using thiol–maleimide coupling chemistry, resulting in the immobilization of ≈105 nanoparticles per cell as determined by confocal microscopy. The ability of these cells to serve as carriers to transport nanoparticles across the BBB is established in vitro and in vivo. Using in vitro BBB models, CD4+ TEM cells are found to be able to transport nanoparticles across the BBB both under static conditions as well as under physiological flow. Finally, upon systemic administration, nanoparticle‐modified T cells are shown to enter the brain parenchyma of mice, demonstrating the brain delivery potential of this T cell subset in allogeneic hosts.

Relay race: The first example of a programmable DNA photonic wire is reported utilizing fluorophore‐tethered pyrrole‐imidazole polyamides for site‐directed fluorophore assembly along a pre‐formed DNA duplex (see scheme; PB=Pacific Blue, Cy3=Cyanine 3; orange rectangles=fluorophore). The importance of such control is revealed by efficient energy transport over distances in excess of 27 nm.

Background: RNA sequencing (RNA-Seq) in its varied forms has become an indispensable tool for analyzing differential gene expression and thus characterization of specific tissues. Aiming to understand the brain barriers genetic signature, RNA seq has also been introduced in brain barriers research. This has led to availability of both, bulk and single-cell RNA-Seq datasets over the last few years. If appropriately performed, the RNA-Seq studies provide powerful datasets that allow for significant deepening of knowledge on the molecular mechanisms that establish the brain barriers. However, RNA-Seq studies comprise complex workflows that require to consider many options and variables before, during and after the proper sequencing process. Main body: In the current manuscript, we build on the interdisciplinary experience of the European PhD Training Network BtRAIN (https ://www.btrai n-2020.eu/) where bioinformaticians and brain barriers researchers collaborated to analyze and establish RNA-Seq datasets on vertebrate brain barriers. The obstacles BtRAIN has identified in this process have been integrated into the present manuscript. It provides guidelines along the entire workflow of brain barriers RNA-Seq studies starting from the overall experimental design to interpretation of results. Focusing on the vertebrate endothelial blood-brain barrier (BBB) and epithelial blood-cerebrospinal-fluid barrier (BCSFB) of the choroid plexus, we provide a step-by-step description of the workflow, highlighting the decisions to be made at each step of the workflow and explaining the strengths and weaknesses of individual choices made. Finally, we propose recommendations for accurate data interpretation and on the information to be included into a publication to ensure appropriate accessibility of the data and reproducibility of the observations by the scientific community. Conclusion: Next generation transcriptomic profiling of the brain barriers provides a novel resource for understanding the development, function and pathology of these barrier cells, which is essential for understanding CNS homeostasis and disease. Continuous advancement and sophistication of RNA-Seq will require interdisciplinary approaches between brain barrier researchers and bioinformaticians as successfully performed in BtRAIN. The present guidelines are built on the BtRAIN interdisciplinary experience and aim to facilitate collaboration of brain barriers researchers with bioinformaticians to advance RNA-Seq study design in the brain barriers community.

Staffellauf: Das erste Beispiel eines programmierbaren photonischen DNA‐Drahtes wurde durch die Verwendung von fluorophormarkierten Pyrrolimidazolpolyamiden zur sequenzgenauen Anordnung von Fluorophoren entlang eines DNA‐Doppelstrangs entwickelt (siehe Schema; PB=Pazifischblau, Cy3=Cyanin 3, orangefarbene Rechtecke=Fluorophor). Der Draht zeigt einen effizienten Energietransport über Entfernungen von mehr als 27 nm.