August 22, 2013
Two weeks ago Nanotechnology News reported on a Nature research article in which scientists used molecular robots to attack specific cells. Though still in its early phases, such technology may carry the potential for targeted treatment of maladies, like cancer and autoimmune disease, whose current treatments harm healthy cells along with the disease-causing ones. How do molecular robots work?
The “robots” we are talking about here are not the microscopic mechanical beings of “gray goo” fame; they are synthetic structures made of DNA strands and antibodies. The DNA strands are produced in the lab using a machine that can assemble them with whatever sequence of A’s, T’s, G’s and C’s the scientist running the machine specifies. Antibodies are proteins that detect foreign invaders in the body (e.g. viruses). They attach to the surface of such cells by means of a specific receptor that fits the antibody in a lock-and-key fashion.
The synthesized DNA-plus-antibody substrates created in the study, called molecular automata, are able to seek out certain cells – those with receptors that match the automata’s antibodies. Once they attach to a cell, a chain of events occurs that effectively “labels” that cell and thus allows scientists to identify and interact with it in a targeted manner.
The outside of a cell is comprised of a membrane and receptors embedded in the membrane. Antibodies and drugs attach to these receptors. It is great when there is a specific receptor for a specific disease. When this happens, a drug with a matching structure can attach to the bad cells and go to work on them, leaving other cells unaffected. Unfortunately, not all diseased or cancerous cells have a unique receptor, so many drugs – including those used to treat rheumatoid arthritis and certain cancers – attack every cell with the relevant receptor, healthy or not.
Sometimes diseased cells will have a couple of receptors that are next to each other that you wouldn’t find next to each other in other, healthy cells. For example, many cells might have a receptor called CD45, but certain diseased or cancerous cells might also have other nearby receptors, such as CD8 and CD3. If there were a way to identify a cell that has this combination of receptors, then maybe it could be tagged for targeted drug delivery.
Researchers at the Hospital for Special Surgery (in collaboration with Columbia University) have come up with a clever way to do this. They took antibodies that attach to certain receptors and attached synthetic DNA tails. Each kind of antibody was joined with strands of DNA whose sequences were designed to complement the strands attached to the other antibodies. If two receptors are next to each other on a specific cell, the automata with antibodies matching those receptors will end up next to each other when they latch onto the cell, and so their respective DNA strands will be next to each other as well. Those DNA strands are attracted to each other because they have complementary sequences. The DNA strands mix together in a predictable way, and the resulting sequence “tags” cells with this combination of receptors.
The experiment reported here is at the “proof-of-concept” stage: The researchers added their automata to a vial of blood and looked for the markers on white blood cells to demonstrate that at least the idea itself is sound. This is an in vitro test. The next step is to see if it works when injected into a mouse, in vivo.
Bioethics issues to consider:
Always with new technologies, there is a question of safety. If this concept works in vivo, and researchers are able to identify tagged cells, the next step will be to see if the automata produce any adverse side-effects.
Additionally, as is the case with things like contrast agents and biological markers, getting the tags into the body is one thing, but getting them out is another. The first question is “Will these automata need to be removed?” The second question is “If so, then how?”
Note:I will be periodically taking one of the news items and breaking down the science into manageable, user-friendly chunks. Oftentimes, understanding the science behind new techniques can help us unpack the ethical issues.