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Targeted drug delivery is a major focus in modern medicine because it allows therapies to act only where needed, reducing side effects and improving effectiveness. Researchers at the University of Washington have taken a significant step forward by creating programmable proteins that can make autonomous “decisions” about where to deliver their therapeutic cargo. Published in Nature Chemical Biology, the study demonstrates that by adding specially designed “tails” to proteins, the proteins can fold into preprogrammed shapes and respond to specific environmental cues, effectively targeting the right cells or tissues.
The team, led by Cole DeForest, senior author and UW professor of chemical engineering and bioengineering, built on earlier work using Boolean logic to control drug release. In the past, drug delivery materials could respond to single biomarkers, but real tissues often share these markers with other areas, leading to off-target effects. The new proteins can respond to combinations of up to five biomarkers simultaneously, acting like logical circuits that only release drugs when the correct conditions are met. This allows much more precise and sophisticated targeting.
Thanks to advances in synthetic biology, the researchers were able to produce these complex proteins quickly and at scale. Instead of months, it now takes just a couple of weeks to go from design to a usable protein. These programmable proteins can be attached to various carriers — hydrogels, beads, or even living cells — and multiple proteins can be loaded on the same carrier, each responding to different cues. The approach could allow therapies to deliver multiple drugs independently within the same treatment.
Looking ahead, DeForest and his team hope to explore additional biomarkers, collaborate on real-world therapeutic applications, and even develop diagnostic tools based on the same principles. While cancer treatment is seen as the first likely application, the technology could eventually enable materials to act with pinpoint precision anywhere in the body.
