They are only 1/10 the size of traditional antibodies, yet they can penetrate the most concealed corners of the human body; They come from alpacas and sharks, but may become a new weapon for humans to fight against stubborn diseases such as cancer, depression, and schizophrenia. They are nanobodies known as "molecular miracles". Scientists from the University of Miami in the United States and the University of Tours in France recently published a paper in the journal Nature Communications, stating that nano antibodies extracted from alpacas exhibited rapid onset, long-lasting, and stable antidepressant effects in a mouse model of stress-induced depression. Research shows that these "small yet strong" nanobodies exhibit the potential to combat various diseases. Major pharmaceutical companies are investing billions of dollars in the development of next-generation nanobody drugs to treat difficult and complex diseases such as cancer, neuropathic pain, and chronic skin diseases, opening new doors for precision medicine. Small stature contains great energy, and all mammals can produce antibodies to resist pathogens. But many years ago, scientists discovered a class of structurally unique and extremely small antibodies in the immune systems of camelids (such as alpacas) and sharks. These antibodies have a molecular weight as small as about 15 kilodaltons and a simpler structure, hence they are called "nanobodies". Scientists from the Medical Center of Mainz University in Germany and the University of Duisburg Essen have pointed out that this type of antibody not only has strong specificity and stability, but also maintains activity in extreme environments such as high temperature and strong acid, making it highly promising for clinical development. More importantly, they can recognize hidden three-dimensional epitopes that traditional antibodies cannot reach, like a precise "molecular key" that opens the door to disease targets. In addition, nanobodies have a simple structure and are easy to genetically engineer. They can be designed in multivalent and bispecific forms, and even serve as drug "couriers" to directly deliver therapeutic molecules to lesions. What is particularly astonishing is that some nanobodies can cross the blood-brain barrier and penetrate deep into the brain, which is of great significance for the treatment of neurological diseases such as brain tumors, Alzheimer's disease, and Parkinson's disease. Nanoantibodies are rapidly transitioning from scientific research tools to clinical weapons, covering multiple battlefields such as cancer, neurological diseases, infectious diseases, autoimmune diseases, etc. At present, the world's first approved nanobody drug, Kaplanuzumab developed by Sanofi, has been used to treat a rare autoimmune hematologic disease. The drug is derived from camel antibodies and is produced on a large scale through genetic engineering, marking the official launch of nanoantibodies on the modern medical stage. AstraZeneca is developing an experimental nanobody for autoimmune diseases in the UK; Eli Lilly and Confo Pharmaceuticals from Belgium have obtained a patent for a new pain management therapy; A new type of nanoantibody developed by Inhibrx company can protect healthy tissues while killing some tumor cells. In a trial targeting rare bone cancer patients, patient survival was significantly prolonged and the risk of disease progression was reduced to half of its original level. It is now being expanded to multiple cancer types for testing. Equally exciting is the breakthrough in the field of mental illness. In July 2024, an international team led by the French National Center for Scientific Research designed a novel nanobody using antibodies derived from alpaca, which can specifically activate the key receptor in the brain closely related to schizophrenia - glutamate receptor. After injection, the memory and behavioral abilities of mice with cognitive impairment were significantly improved, and the efficacy lasted for more than a week. In addition, the team led by Wu Xilin from Nanjing University School of Medicine in China spent 9 years screening a set of highly efficient and broad-spectrum nanoantibodies from alpaca bodies, which can effectively neutralize the tick disease virus. In the ferret model simulating the immune status of elderly people, this combination therapy showed excellent efficacy. In the face of virus infection, including COVID-19, nano antibodies are not absent. A paper published in the Journal of Nanobiotechnology reveals that shark nanobodies have shown great potential in treating various viral infections. At present, multiple research teams have developed candidate antibodies that can bind to viral spike proteins, demonstrating strong neutralizing ability. Some candidate antibodies have entered clinical trials. As Sanofi's Chief Scientific Officer Michael Quigley has said, these tiny antibodies from animals such as alpacas and sharks may play a major role in many future drugs. To promote the implementation of "one person, one policy" and look to the future, nanobodies will not only be "targeted missiles", but also become the core component of intelligent medical platforms. Scientists are trying to combine it with gene editing technologies such as CRISPR Cas to create a "nanobody CRISPR" fusion system, achieving precise regulation of specific genes; There are also teams exploring the construction of supramolecular nanobody assemblies for use in fields such as synthetic biology and biomolecule factories. The addition of AI has further accelerated this process. Through AI driven design and affinity optimization, scientists can quickly screen for personalized antibodies that are most suitable for patients, promoting precise treatment with "one person, one policy". At the same time, nanobodies have the potential to work together with CAR-T cell therapy and nanomaterial delivery systems, continuously expanding the boundaries of treatment and challenging targets that were once considered "untreatable". Nanoantibodies are small in size, but they contain the power to overcome obstacles, and they have the potential to alleviate medical difficulties with the power of "pulling a thousand pounds with four or two". (New Society)