Investigators from New York’s Hospital for Special Surgery (HSS) and Columbia University have come up with a science fiction-esque solution for developing targeted therapeutics—they’re using molecular “robots” to make contact with specific cells.

Writing in Nature Nanotechnology, the HSS-Columbia team describes molecular automata—mixtures of molecules that undergo strictly defined structural changes in response to sequential interactions with inputs—based on antibody-directed strain-displacement cascades, which can analyze cells based on surface markers. “The final output of a molecular automaton that successfully completes its analysis is the presence of a unique molecular tag on the cell surface of a specific subpopulation of lymphocytes within human blood cells,” Columbia’s Milan Stojanovic, Ph.D., and his colleagues write.

The researchers used these molecular automata to target receptors on the surfaces of specific lymphocytes. They created three automata, each with a DNA and antibody component of either CD45, CD3, or CD8. Then, introducing these molecular complexes to blood samples from healthy humans, the researchers found that they did indeed identify the presence or absence of cell surface markers as was expected. “These results extend the use of molecular automata beyond analysis by transfecting oligonucleotides into cells, thereby permitting new operations on the surfaces of native cells,” Dr. Stojanovic et al. write. “The demonstrated systems also contribute to the emerging field of molecular robotics,” they add.

“The reactions occur fast. In about 15 minutes, we can label cells,” Maria Rudchenko, a research associate at HSS, said in a statement. Added her colleague, HSS’ Sergei Rudchenko, Ph.D.: “This is a proof-of-concept study that it works in human whole blood. The next step is to test it in animals.”

“Autonomous molecular cascades for evaluation of cell surfaces” was published July 28 in Nature Nanotechnology.

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