Using a technique called “DNA origami”, US scientists have made programmable molecule-transporting nanorobots that can seek out particular cell targets and deliver specific instructions for them to follow. One example of such use could be to tell cancer cells to destroy themselves. The researchers write about their findings in Friday’s online issue of Science.
The programmable nanorobots carry cargoes of molecules that are released when aptamers (peptide molecules that bind to a specific target) in their structure bind to specific proteins on the surface of targeted cells.
Researchers at the Wyss Institute for Biologically Inspired Engineering at Harvard University modeled the technology on the immune system’s white blood cells that patrol the bloodstream, looking for signs of trouble. They hope one day it will be used to program immune responses to treat diseases.
The DNA origami method is one that folds strands of DNA into complex three-dimensional shapes.
This latest study is considered a breakthrough because it brings together recent advances in DNA origami that have been pioneered in research centres around the world, not just at the Wyss Institute, to try and meet the challenge of how to kill cancer cells in a highly selective way.
First author Dr Shawn Douglas, a Wyss Technology Development Fellow when he worked on the study, and colleagues, devised their nanosized robot in the shape of an open barrel made of two halves joined by a hinge. (Douglas is now an Assistant Professor in the Faculty of Life Sciences and the Nano-Center at Bar-Ilan University in Israel).
The two halves are held shut by special DNA latches that respond to particular targets by allowing the two halves to swing open and expose their payload.
The targets the latches respond to are particular combinations of cell-surface proteins: for example these could be disease markers.
The DNA barrel can contain various payloads. Examples include molecules with specific instructions that receptors on cell surfaces respond to, causing them to change the signals they send to the cells.
The researchers demonstrated the technology on cells from two types of cancer: leukemia and lymphoma. The message encoded in the payload was to activate the cells’ suicide switch. This triggers a standard feature of all cells, called apoptosis, which allows aging or abnormal cells to be eliminated.
Leukemia and lymphoma cells don’t speak the same language, so the suicide triggering instructions had to be encoded in different antibody combinations.
Senior author Dr George Church, a Wyss core faculty member and Professor of Genetics at Harvard Medical School, told the press:
“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.”
The versatility of the technology emulates that of white blood cells that have the ability to sense a whole range of cell distress signals, bind to the cells, and then transmit the appropriate self-destruct instructions in the language of that cell type.
The DNA nanorobot uses modular components to achieve a similar range of versatility: different hinges, different molecular payloads. These can be switched in and out of the underlying “chassis”, rather like swapping various engines and tires in and out of cars.
Such a system should have the potential to treat a variety of diseases. DNA nanotechnology is widely recognized as a potential way to deliver drugs and molecular signals: another plus is it is biodegradable.
But there are considerable challenges in how to program this tiny machine, never mind how to make the right structure, then get it to open and close, then re-open, insert, carry and deliver the payload.
The study represents a big step forward in meeting these challenges because three new elements have been combined for the first time. One of these is because the DNA barrel has no lids, the payloads can be inserted from the side in one step: there is no need to open and then close the barrel.
The second new element is that this system uses latches that respond to proteins (not DNA or RNA like other systems), which are commonly found on cell surfaces. And the third new element is that it uses antibody fragments to send the molecular signals, so by using different combinations of these, different types of immune responses can be replicated to target specific diseases.
Written by Catharine Paddock PhD