Mechanism-guided engineering of a minimal biological particle for genome editing.

The widespread application of genome editing to treat and cure disease requires the delivery of genome editors into the nucleus of target cells. Enveloped delivery vehicles (EDVs) are engineered virally derived particles capable of packaging and delivering CRISPR-Cas9 ribonucleoproteins (RNPs). However, the presence of lentiviral genome encapsulation and replication proteins in EDVs has obscured the underlying delivery mechanism and precluded particle optimization.

Hidden: A Baker's Dozen Ways in Which Research Reporting is Less Transparent than it Could be and Suggestions for Implementing Einstein's Dictum.

The tutelage of our mentors as scientists included the analogy that writing a good scientific paper was an exercise in storytelling that omitted unessential details that did not move the story forward or that detracted from the overall message. However, the advice to not get lost in the details had an important flaw. In science, it is the many details of the data themselves and the methods used to generate and analyze them that give conclusions their probative meaning.

Colocalization of Cancer-Associated Biomarkers on Single Extracellular Vesicles for Early Detection of Cancer.

Detection of cancer early, when it is most treatable, remains a significant challenge because of the lack of diagnostic methods sufficiently sensitive to detect nascent tumors. Early-stage tumors are small relative to their tissue of origin, heterogeneous, and infrequently manifest in clinical symptoms. The detection of early-stage tumors is challenging given the lack of tumor-specific indicators (ie, protein biomarkers, circulating tumor DNA) to enable detection using a noninvasive diagnostic assay.

Intercellular transmission of alpha-synuclein.

An emerging theme in Parkinson's disease (PD) is the propagation of α-synuclein pathology as the disease progresses. Research involving the injection of preformed α-synuclein fibrils (PFFs) in animal models has recapitulated the pathological spread observed in PD patients. At the cellular and molecular levels, this intercellular spread requires the translocation of α-synuclein across various membrane barriers.

Calpains Orchestrate Secretion of Annexin-containing Microvesicles during Membrane Repair.

Microvesicles (MVs) are membrane-enclosed, plasma membrane-derived particles released by cells from all branches of life. MVs have utility as disease biomarkers and may participate in intercellular communication; however, physiological processes that induce their secretion are not known. Here, we isolate and characterize annexin-containing MVs and show that these vesicles are secreted in response to the calcium influx caused by membrane damage.