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Sending DNA robot to do the job

Article / Review by on February 16, 2012 – 9:01 pmNo Comments

Sending DNA robot to do the job
Technology has potential to seek out cancer cells, cause them to self-destruct

Researchers at the Wyss Institute for Biologically Inspired Engineering at Harvard University have developed a robotic device made from DNA that could potentially seek out specific cell targets within a complex mixture of cell types and deliver important molecular instructions, such as telling cancer cells to self-destruct. Inspired by the mechanics of the body’s own immune system, the technology might one day be used to program immune responses to treat various diseases. The research findings appear today in Science.

Using the DNA origami method, in which complex 3-D shapes and objects are constructed by folding strands of DNA, Shawn Douglas, a Wyss Technology Development Fellow, and Ido Bachelet, a former Wyss postdoctoral fellow who is now an assistant professor in the Faculty of Life Sciences and the Nano-Center at Bar-Ilan University in Israel, created a nanosized robot in the form of an open barrel whose two halves are connected by a hinge. The DNA barrel, which acts as a container, is held shut by special DNA latches that can recognize and seek out combinations of cell-surface proteins, including disease markers. When the latches find their targets, they reconfigure, causing the two halves of the barrel to swing open and expose its contents, or payload.  The container can hold various types of payloads, including specific molecules with encoded instructions that can interact with specific cell surface signaling receptors.

Douglas and Bachelet used this system to deliver instructions, which were encoded in antibody fragments, to two different types of cancer cells — leukemia and lymphoma. In each case, the message to the cell was to activate its “suicide switch” — a standard feature that allows aging or abnormal cells to be eliminated. And because leukemia and lymphoma cells speak different languages, the messages were written in different antibody combinations.

This programmable nanotherapeutic approach was modeled on the body’s own immune system in which white blood cells patrol the bloodstream for any signs of trouble. These infection fighters are able to home in on specific cells in distress, bind to them, and transmit comprehensible signals to direct them to self-destruct. The DNA nanorobot emulates this level of specificity through the use of modular components in which different hinges and molecular messages can be switched in and out of the underlying delivery system, much as different engines and tires can be placed on the same chassis. The programmable power of this type of modularity means the system has the potential to one day be used to treat a variety of diseases.

“We can finally integrate sensing and logical computing functions via complex, yet predictable, nanostructures — some of the first hybrids of structural DNA, antibodies, aptamers, and metal atomic clusters — aimed at useful, very specific targeting of human cancers and T-cells,” said George Church, a Wyss core faculty member and professor of genetics at Harvard Medical School, who is principal investigator on the project.

Because DNA is a natural biocompatible and biodegradable material, DNA nanotechnology is widely recognized for its potential as a delivery mechanism for drugs and molecular signals. But there have been significant challenges to its implementation, such as what type of structure to create; how to open, close, and reopen that structure to insert, transport, and deliver a payload; and how to program this type of nanoscale robot.

By combining several novel elements for the first time, the new system represents a significant advance in overcoming these implementation obstacles. For instance, because the barrel-shaped structure has no top or bottom lids, the payloads can be loaded from the side in a single step — without having to open the structure first and then reclose it. Also, while other systems use release mechanisms that respond to DNA or RNA, the novel mechanism used here responds to proteins, which are more commonly found on cell surfaces and are largely responsible for transmembrane signaling in cells. Finally, this is the first DNA-origami-based system that uses antibody fragments to convey molecular messages — a feature that offers a controlled and programmable way to replicate an immune response or develop new types of targeted therapies.

“This work represents a major breakthrough in the field of nanobiotechnology as it demonstrates the ability to leverage recent advances in the field of DNA origami pioneered by researchers around the world, including the Wyss Institute’s own William Shih, to meet a real-world challenge, namely killing cancer cells with high specificity,” said Wyss Institute Founding Director Donald Ingber. Ingber is also the Judah Folkman Professor of Vascular Biology at Harvard Medical School and the Vascular Biology Program at Children’s Hospital Boston, and professor of bioengineering at Harvard’s School of Engineering and Applied Sciences. “This focus on translating technologies from the laboratory into transformative products and therapies is what the Wyss Institute is all about.”

By Twig Mowatt
Wyss Institute Communications

Image courtesy of the Wyss Institute

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About Harvard Medical School (HMS)

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“Since 1872, Harvard Medical School has been the incubator of bold ideas—a place where extraordinary people advance education, science and health care with unrelenting passion.

Whether training tomorrow’s doctors and scientists, decoding the fundamental nature of life, advancing patient care or improving health delivery systems around the world, we are never at rest. Allied with some of the world’s best hospitals, research institutes and a University synonymous with excellence, the School’s mission remains as ambitious as it is honorable: to alleviate human suffering caused by disease.”

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About Harvard School of Public Health (HSPH)

Harvard School of Public Health is dedicated to advancing the public’s health through learning, discovery and communication. More than 400 faculty members are engaged in teaching and training the 1,000-plus student body in a broad spectrum of disciplines crucial to the health and well being of individuals and populations around the world. Programs and projects range from the molecular biology of AIDS vaccines to the epidemiology of cancer; from risk analysis to violence prevention; from maternal and children’s health to quality of care measurement; from health care management to international health and human rights.

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About Harvard University.

Established in 1636, Harvard is the oldest institution of higher education in the United States. The University, which is based in Cambridge and Boston, Massachusetts, has an enrollment of over 20,000 degree candidates, including undergraduate, graduate, and professional students. Harvard has more than 360,000 alumni around the world.

Harvard University is devoted to excellence in teaching, learning, and research, and to developing leaders in many disciplines who make a difference globally. Harvard faculty are engaged with teaching and research to push the boundaries of human knowledge. For students who are excited to investigate the biggest issues of the 21st century, Harvard offers an unparalleled student experience and a generous financial aid program, with over $160 million awarded to more than 60% of our undergraduate students. The University has twelve degree-granting Schools in addition to the Radcliffe Institute for Advanced Study, offering a truly global education.

‘Universities nurture the hopes of the world: in solving challenges that cross borders; in unlocking and harnessing new knowledge; in building cultural and political understanding; and in modeling environments that promote dialogue and debate… The ideal and breadth of liberal education that embraces the humanities and arts as well as the social and natural sciences is at the core of Harvard’s philosophy. ’/ Drew Gilpin Faust

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* The above story is adapted from materials provided by Harvard University

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