Recent advances in medical treatments have been revolutionary in shaping the management and treatment landscape of patients, notably cancer patients. Over the last decade, patients with diverse forms of locally advanced or metastatic cancer, such as melanoma, lung cancers, and many blood-borne malignancies, have seen their life expectancies increasing significantly. Notwithstanding these encouraging results, the present-day struggle with these treatments concerns patients who remain largely unresponsive, as well as those who experience severely toxic side effects. Gaining deeper insight into the cellular and molecular mechanisms underlying these variable responses will bring us closer to developing more effective therapeutics. To assess these mechanisms, non-invasive imaging techniques provide valuable whole-body information with precise targeting. An example of such is immuno-PET (Positron Emission Tomography), which employs radiolabeled antibodies to detect specific molecules of interest. Nanobodies, as the smallest derived antibody fragments, boast ideal characteristics for this purpose and have thus been used extensively in preclinical models and, more recently, in clinical early-stage studies as well. Their merit stems from their high affinity and specificity towards a target, among other factors. Furthermore, their small size (~14 kDa) allows them to easily disperse through the bloodstream and reach tissues in a reliable and uniform manner. In this review, we will discuss the powerful imaging potential of nanobodies, primarily through the lens of imaging malignant tumors but also touching upon their capability to image a broader variety of nonmalignant diseases.

Detection and diagnosis of bloodborne pathogens are critical for patients and for preventing outbreaks, yet challenging due to these diseases’ nonspecific initial symptoms. We previously advanced CRISPR-based Combinatorial Arrayed Reactions for Multiplexed Evaluation of Nucleic acids (CARMEN) technology for simultaneous detection of pathogens on numerous samples. Here, we develop three CARMEN panels that target viral hemorrhagic fevers, mosquito-borne viruses, and sexually transmitted infections, collectively identifying 23 pathogens. We use deep learning to design CARMEN assays with enhanced sensitivity and specificity, validating them and evaluating their performance on synthetic targets, spiked healthy normal serum samples, and patient samples for Neisseria gonorrhoeae in the United States and for Lassa and mpox virus in Nigeria. Our results show multiplexed CARMEN assays match or outperform individual assay RT-qPCR in sensitivity, with matched specificity. These findings underscore CARMEN’s potential as a highly effective tool for accurate pathogen detection for clinical diagnosis and public health surveillance.

Emergency Use Authorization (EUA) allows the US Food and Drug Administration (FDA) to expedite the availability of therapeutics in the context of a public health emergency. To date, an evidentiary standard for clinical efficacy to support an EUA has not yet been established. This review examines the clinical data submitted in support of EUA for antiviral and anti-inflammatory therapeutics for coronavirus disease 2019 (COVID-19) through December of 2021 and the resilience of the authorization as new clinical data arose subsequent to the authorization. In the vast majority of cases, EUA was supported by at least one well-powered randomized controlled trial (RCT) where statistically significant efficacy was demonstrated. This included branded medications already approved for use outside of the context of COVID-19. When used, the standard of a single RCT seemed to provide adequate evidence of clinical efficacy, such that subsequent clinical studies generally supported or expanded the EUA of the therapeutic in question. The lone generic agent that was granted EUA (chloroquine/hydroxychloroquine) was not supported by a well-controlled RCT, and the EUA was withdrawn within 3 months time. This highlighted not only the ambiguity of the EUA standard, but also the need to provide avenues through which high quality clinical evidence for the efficacy of a generic medication could be obtained. Therefore, maintaining the clinical trial networks assembled during the COVID-19 pandemic could be a critical component of our preparation for future pandemics. Consideration could also be given to establishing a single successful RCT as regulatory guidance for obtaining an EUA.