Distinguishing Protein and Gene Delivery Enables Characterization and Bioengineering of Extracellular Vesicle-Adeno-Associated Virus Vectors.

Adeno-associated virus (AAV) gene therapies have achieved clinical success, with multiple products reaching regulatory approval. Encapsulation of AAV vectors within engineered extracellular vesicles (EVs) is an emerging strategy which could help overcome challenges including pre-existing anti-capsid immunity and the need for controlling targeting and tropism. To guide the development of EV-AAV technologies, we developed an assay for quantifying and controlling for the contribution of pseudotransduction to evaluations of EV-AAV-mediated gene delivery.

Engineered Feedback Employing Natural Hypoxia-Responsive Factors Enhances Synthetic Hypoxia Biosensors.

Inadequate oxygen supply is a feature of multiple acute and chronic diseases, and hypoxia biosensors can be deployed in engineered cells to study or treat disease. Although mediators of hypoxia-responsiveness have been characterized, dynamics of this response are less understood, and there is no general approach for tuning biosensor performance to meet application-specific needs. To address these gaps, we investigated the use of genetic circuits to enhance biosensor performance through feedback, ultimately achieving both low background and amplified hypoxia-induced gene expression.

Skin-resident immune cells actively coordinate their distribution with epidermal cells during homeostasis.

Organs consist of multiple cell types that ensure proper architecture and function. How different cell types coexist and interact to maintain their homeostasis in vivo remains elusive. The skin epidermis comprises mostly epithelial cells, but also harbours Langerhans cells (LCs) and dendritic epidermal T cells (DETCs).

Computation-guided optimization of split protein systems.

Splitting bioactive proteins into conditionally reconstituting fragments is a powerful strategy for building tools to study and control biological systems. However, split proteins often exhibit a high propensity to reconstitute, even without the conditional trigger, limiting their utility. Current approaches for tuning reconstitution propensity are laborious, context-specific or often ineffective.

Tissue-scale coordination of cellular behaviour promotes epidermal wound repair in live mice.

Tissue repair is fundamental to our survival as tissues are challenged by recurrent damage. During mammalian skin repair, cells respond by migrating and proliferating to close the wound. However, the coordination of cellular repair behaviours and their effects on homeostatic functions in a live mammal remains unclear.

miR-155 Is Essential for Inflammation-Induced Hippocampal Neurogenic Dysfunction.

Peripheral and CNS inflammation leads to aberrations in developmental and postnatal neurogenesis, yet little is known about the mechanism linking inflammation to neurogenic abnormalities. Specific miRs regulate peripheral and CNS inflammatory responses. miR-155 is the most significantly upregulated miR in primary murine microglia stimulated with lipopolysaccharide (LPS), a proinflammatory Toll-Like Receptor 4 ligand.

Are complications of transrectal ultrasound-guided biopsies of the prostate gland increasing?

Although transrectal ultrasound-guided biopsies (TRUSB) of the prostate gland are generally considered to be low-risk procedures, a study from Canada reported that there had been a significant increase in the percentage of hospital admissions following TRUSBs between 1996 and 2005 (1.0% to 4.1%).