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Researchers at the University of Washington in Seattle and the University of California, Los Angeles (UCLA) have developed a computational approach to designing specialized proteins that assemble themselves to form nanoparticle cages that can be used to deliver drugs to tumors and other sites of disease. Published in the journal Science, this research could be utilized to create nanoparticle cages from any number of different proteins, with potential applications across the fields of medicine and molecular biology.
UCLA investigator David Yeates led this study. He and his colleagues used computer models to identify two proteins that could be combined to form perfectly-shaped three-dimensional puzzle pieces. Twelve of these specialized pieces fit together to create a molecular cage a mere fraction of the size of a virus.
The specifically designed proteins intermesh to form a hollow lattice that could act as a vessel for drug delivery. In principle, it would be possible to attach a recognition sequence for cancer cells on the outside of the cage together with a chemotherapeutic agent. As currently designed, the assembled protein cages are porous enough that a drug placed inside would likely leak out during the delivery process. The investigators are now conducting computer modeling studies to design a new molecular cage with an interior that will be better sealed.
In a second paper that was also published in Science, Dr. Yeates and University of Washington colleague David Baker describe how they created similarly designed molecular cages using multiple copies of the same protein as building blocks. The scientists control the shape of the cage by computing the sequence of amino acids necessary to link the proteins together at the correct angles. This alternative method represents a more versatile approach in theory because it requires only one type of protein to form a structure, Dr. Yeates said.
About The National Cancer Institute (NCI)
To help meet the goal of reducing the burden of cancer, the National Cancer Institute (NCI), part of the National Institutes of Health, is engaged in efforts to harness the power of nanotechnology to radically change the way we diagnose, treat and prevent cancer.
The NCI Alliance for Nanotechnology in Cancer is a comprehensive, systematized initiative encompassing the public and private sectors, designed to accelerate the application of the best capabilities of nanotechnology to cancer.
Currently, scientists are limited in their ability to turn promising molecular discoveries into benefits for cancer patients. Nanotechnology can provide the technical power and tools that will enable those developing new diagnostics, therapeutics, and preventives to keep pace with today’s explosion in knowledge.
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