Programmed cell death protein 1 (PD-1) is an important immunosuppressive receptor expressed mainly on T cells, B cells, natural killer cells, and other immune cells. PD-1 exerts its inhibitory function by binding to its ligands PD-L1 and PD-L2. In normal immune responses, the activation of PD-1 serves as a self-protective mechanism to prevent an overactive immune system, helping to avoid attacks on self-tissues. However, during tumor immune escape, tumor cells upregulate PD-L1 expression to bind with PD-1, inhibiting T cell activity and thereby evading immune surveillance. Furthermore, abnormal activation of PD-1 also plays a significant role in autoimmune diseases. Through the interaction between PD-1 and its ligands, immune cell activity is suppressed, preventing the immune system from effectively clearing abnormal self-cells or tissues, which is an important mechanism in the development of various autoimmune diseases.

G protein-coupled receptors (GPCRs) are one of the most important signal transduction protein families in human cell membranes, regulating a wide range of physiological processes from vision and olfaction to cardiovascular function. Among them, the Angiotensin II Type 1 Receptor (AT1R) plays a central role in blood pressure regulation, fluid balance, and cardiovascular diseases. However, the activation mechanism of peptide ligand-binding GPCRs like AT1R has long been a research bottleneck, as traditional methods struggled to capture their active conformations, hindering the precise development of targeted therapeutics. A research team from Harvard Medical School, Duke University, and other institutions has successfully overcome this challenge using synthetic nanobody technology. Their findings, published in Cell, pave a new path for GPCR research and drug development.

CD7 is a transmembrane glycoprotein primarily expressed on the surface of T cells, NK cells, and their precursor cells. It is highly expressed, especially in hematological tumors such as T-cell acute lymphoblastic leukemia (T-ALL) and lymphoma. As a member of the immunoglobulin superfamily, CD7 is involved in T cell activation, adhesion, and signal transduction, playing an important role in lymphocyte development and immune response. It is a significant marker for T-cell malignancies. Due to its specific expression and persistence in pathological states, CD7 has become an ideal target for developing novel immunotherapeutic strategies.

Vesicular stomatitis virus (VSV) is a highly promising oncolytic virus capable of preferentially replicating in and lysing tumor cells with defective interferon signaling pathways. Its glycoprotein (VSV-G) is the most commonly used envelope glycoprotein for pseudotyping lentiviral vectors and is widely utilized in gene therapy research. However, the natural receptors of VSV-G (the LDL-R family) are expressed on the surface of nearly all cell types, leading to a lack of targeting specificity for both VSV and pseudotyped lentiviruses. This not only results in the infection of normal cells, causing off-target toxicity, but also reduces the efficacy of precise in vivo treatments. It is known that mutations at the K47 and R354 residues of VSV-G can completely abolish its binding to LDL-R while preserving its fusion activity, offering a potential strategy for engineering targeted VSV-G.