Scientists at Harvard University’s Wyss Institute for Biologically
Inspired Engineering said they have developed a robotic device made from
DNA that could potentially seek specific cell targets and deliver
important molecular instructions, such as telling cancer cells to
self-destruct.
The researchers said in a press release they were inspired by the
mechanics of the body’s immune system. The technology may some day be
used to program immune responses to treat various diseases, they wrote
in today’s issue of Science.
“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,” George
Church, a Wyss faculty member and principal investigator on the project,
said in a statement.
Using the DNA origami method, in which complex three-dimensional shapes
and objects are constructed by folding strands of DNA, the researchers
created a nanosized robot that looks like an open barrel with its halves
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 the contents or “payload.” The
container can hold various types of payloads, including certain
molecules with encoded instructions that can interact with specific cell
surface signaling receptors.
The scientists used the system to deliver instructions, which were
encoded in antibody fragments, to two different types of cancer cells,
leukemia and lymphoma. Both cell types were instructed to activate their
suicide switch, a naturally occurring feature that allows aging or
abnormal cells to be eliminated in a process called apoptosis. Because
leukemia and lymphoma cells essentially speak different languages, the
messages were written in different antibody combinations.
The programmable nanotherapeutic approach was modeled on the body’s
immune system, where white blood cells patrol the bloodstream for signs
of trouble. The infection fighters can hone in on specific cells in
distress, bind to them, and transmit comprehensible signals to
self-destruct. The DNA nanorobot emulates this level of specificity
using 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 researchers noted. Because this approach is programmable, the
scientists said the system has the potential to treat a variety of
diseases.
DNA is a natural biocompatible and biodegradable material, so DNA
nanotechnology has been seen as a potential delivery mechanism for drugs
and molecular signals, the researchers said. But implementing it has
been a challenge, including knowing what type of structure to create,
how to program a nanoscale robot, and how to open, close, and reopen
that structure to insert, transport, and deliver a payload. The
scientists said they have combined several novel elements for the first
time to overcome these obstacles. The barrel-shaped structure, for
example, has no top or bottom lids, so the payloads can be loaded from
the side in a single step without having to open and then reclose it.
In addition, other systems use release mechanisms that respond to DNA or
RNA, but the researchers said their mechanism responds to proteins,
which are more commonly found on cell surfaces and are largely
responsible for transmembrane signaling in cells. They also said this is
the first DNA-origami-based system that uses antibody fragments to
convey molecular messages so that there is a controlled, programmable
way to replicate an immune response or develop new types of targeted
therapies.
Source: http://www.masshightech.com/stories/2012/02/13/daily42-Harvard-DNA-nanorobot-may-find-kill-cancer-cells.html
