American researchers have used molecular robots to develop a new technique, which can lead to the development of more targeted drugs.
Sergei Rudchenko, Ph.D., director of flow cytometry at Hospital for Special Surgery (HSS) in New York City and a senior author of the study, said that the next step is to conduct tests in a mouse model of leukemia.
In the new study, which is a collaboration between researchers from HSS and Columbia University, scientists designed molecular robots that are capable of identifying multiple receptors on cell surfaces, thereby effectively labeling more specific subpopulations of cells.
The molecular robots, known as molecular automata, are composed of a mixture of antibodies and short strands of DNA. These short DNA strands, otherwise called oligonucleotides, can be manufactured by researchers in a laboratory with any user-specified sequence.
The researchers conducted their experiments using white blood cells. All white blood cells have CD45 receptors, but only subsets have other receptors such as CD20, CD3, and CD8.
In one experiment, HSS researchers created three different molecular robots. Each one had an antibody component of either CD45, CD3 or CD8 and a DNA component.
The DNA components of the robots were created to have a high affinity to the DNA components of another robot. DNA can be thought of as a double stranded helix that contains two strands of coded letters, and certain strands have a higher affinity to particular strands than others.
The researchers mixed human blood from healthy donors with their molecular robots. When a molecular robot carrying a CD45 antibody latched on to a CD45 receptor of a cell and a molecular robot carrying a CD3 antibody latched on to a different welcoming receptor of the same cell, the close proximity of the DNA strands from the two robots triggered a cascade reaction, where certain strands were ripped apart and more complementary strands joined together.
The result was a unique, single strand of DNA that was displayed only on a cell that had these two receptors.
The addition of a molecular robot carrying a CD8 antibody docking on a cell that expressed CD45, CD3 and CD8 caused this strand to grow. The researchers also showed that the strand could be programmed to fluoresce when exposed to a solution.
The robots can essentially label a subpopulation of cells allowing for more targeted therapy. The researchers say the use of increasing numbers of molecular robots will allow researchers to zero in on more and more specific subsets of cell populations. In computer programming language, the molecular robots are performing what is known as an "if yes, then proceed to X function."
Maria Rudchenko, M.S., the first author of the paper and a research associate at Hospital for Special Surgery, said that the automata trigger the growth of more strongly complementary oligonucleotides.
She said that the reactions occur fast. In about 15 minutes, we can label cells.
The findings are in Advance Online Publication on the website of Nature Nanotechnology.