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The Victims' Counterattack: How did Crews deliver disease-causing proteins into the cell's 'scavenger'?
When we face diseases, scientists often seek innovative solutions to fight them. Craig M. Crews, a chemical biology researcher at Yale University, is one such courageous scientist. His research focuses on delivering target proteins into the cell's scavenger system, thereby achieving effective clearance of disease-causing proteins. This technology not only improves treatment efficiency, but also provides new hope for diseases that were previously considered "untreatable."
The key to solving the problem lies in how to cleverly utilize the cell's own scavenger mechanism.
From Basics to Breakthroughs: Crews’ Academic Journey
After receiving his bachelor's degree in chemistry from the University of Virginia in 1986, Crews conducted research at the University of Tübingen on a German Academic Exchange Service (DAAD) scholarship. He then completed his graduate studies in the laboratory of Raymond Erikson at Harvard University, where he successfully purified and cloned the MAP kinase kinase MEK1, a key signaling molecule that is closely involved in cancer-related cell proliferation and survival processes. As time went on, Crews joined Yale University in 1995 as an assistant professor.
Reshaping treatment methods: the birth of PROTAC technology
In 2001, Crews collaborated with Ray Deshaies to develop PROTAC technology, a new technology that uses the cell quality control system to induce protein degradation. These heterobifunctional molecules can simultaneously bind to target proteins and ubiquitin ligases, thereby initiating ubiquitination of the target proteins and sending them to the proteasome for degradation.
Expanded applications: Hope from cancer to neurodegenerative diseasesThis innovation not only expands the boundaries of medicinal chemistry, but also makes "undruggable" proteins targets for treatment.
Crews' research extends beyond cancer. Following the success of PROTAC technology, he founded several biotech companies dedicated to treating cancer, neurodegenerative diseases and other diseases. For example, he founded Arvinas in 2013, a company that uses PROTAC technology to develop a variety of drugs for different diseases. These drugs have shown good safety and efficacy in clinical trials, providing new treatment options for patients with more severe symptoms.
Latest progress: PROTAC drugs in clinical trials
As of 2023, Arvinas has put three PROTAC drugs into clinical trials, the most advanced of which is ARV-471, which targets the estrogen receptor. This drug is currently undergoing phase III clinical trials, hoping to bring good news to patients with metastatic breast cancer. In addition, Arvinas has collaborated with Pfizer to jointly develop this potential treatment option, further promoting the application and development of PROTAC.
Crews' research shows that using small molecule drugs to induce protein degradation is an important trend in future drug discovery.
Driving industry innovation: Crews’ multiple biotech companies
Crews also founded several biotech companies based on his research at Yale, such as Halda Therapeutics and Siduma Therapeutics, to develop other novel drug technologies. The purpose of these technologies is to precisely control the interactions between proteins to achieve therapeutic effects. These companies not only continue to innovate in cancer treatment, but also leave a deep mark in the corresponding markets.
Awards and Honors: Continuous Professional Influence
Crews has received numerous awards for his contributions to drug discovery, including the AAAS Fellowship and the Conncticut Technology Award. Behind these honors are his unremitting efforts and professional pursuit.
Conclusion: Future Directions
Crews' success lies not only in the innovation of the technology itself, but also in how to apply these technologies to actual disease treatment. His engineering philosophy and cross-border cooperation model will further promote the innovation of the biotechnology industry and pave the way for future medical development. With his efforts in drug development and disease treatment, we can't help but wonder: how many more "untreatable" diseases will be overcome in the near future?
