The lack of effective treatments for brain disorders related to NMDA receptor hypofunction, such as schizophrenia and GRIN1-related disorders, has long been a major challenge in the medical field. Traditional small-molecule drugs often lack selectivity and exhibit significant side effects, while antibody-based therapies struggle to cross the blood-brain barrier (BBB), limiting their efficacy.To address this clinical need, a collaborative effort involving the Institute of Functional Genomics in Montpellier (France), the Department of Pharmacology and Toxicology at the University of Toronto (Canada), and the Faculty of Health, Medicine, and Technology at Paris-Saclay University (France) has developed a bivalent bispecific nanobody named DN13-DN1. Administered via intraperitoneal (IP) injection, this nanobody successfully crosses the BBB, specifically binds to and enhances the activity of the mGlu2 receptor. In two mouse models of NMDA receptor hypofunction—neonatal PCP-induced (mimicking schizophrenia) and GluN1-KD genetic (mimicking GRIN1 disorder)—DN13-DN1 significantly improved cognitive deficits and sensorimotor gating impairments. Subchronic treatment demonstrated stable therapeutic effects without noticeable side effects, outperforming both traditional small-molecule drugs and IgG-class antibodies. This study was published in the leading academic journal Nature. Let’s delve into the details.

In modern medical diagnostics and life science research, proteins serve as key biomarkers directly linked to disease phenotypes, making their accurate and rapid detection highly important. However, conventional detection technologies face multiple limitations. For example, immunoassays such as ELISA require tedious separation and washing steps or depend on stringent conditions for antibody pairs, making it difficult to meet the needs of point-of-care testing and high-throughput analysis. Although mass spectrometry is considered the "gold standard" in proteomics research, it relies on large, expensive equipment and involves lengthy analytical procedures.

In the long-standing battle between humans and viruses, the continuous mutation of viruses resembles an arms race where “as virtue rises one foot, vice rises ten.” As the shadow of the COVID-19 pandemic gradually recedes, we are still not entirely free from the threat posed by coronaviruses. The emergence of new viral variants continues to challenge global public health security. Against this backdrop, a research team comprising multiple world-renowned institutions, including the University of Pittsburgh, has successfully screened a type of pan-sarbecovirus nanobody (psNbs) with "super immunity" from immunized alpacas using innovative technological approaches. This study, published in Cell Reports, aims to identify a universal solution capable of combating an entire virus family.

In plant biology research, deciphering protein localization, interactions, and dynamics is central to unraveling life's mechanisms. Traditional protein tagging techniques relying on fluorescent proteins or epitope tags are often hindered by large tag size, insufficient affinity, or limited applicability. This is particularly problematic for "hard-to-tag" proteins such as multi-pass transmembrane proteins (e.g., metal transporters) and functionally sensitive proteins, where traditional methods can disrupt their structure and function, bringing research to a halt. Nanobodies, with their advantages of high affinity and genetic encodability, offer a potential solution to this bottleneck. While the ALFA tag and ALFA nanobody system have previously demonstrated excellent performance in animal and yeast cells, their applicability in plants had not been systematically evaluated.