The artistic expression of two antibodies that trigger two chemical reactions. Image Credit: Illustration by Oscar Melendre Hoyos
Researchers have developed a strategy to synthesize functional molecules with specific diagnostic antibodies.
Antibodies are outstanding biomarkers: they are reminders that provide us with signs of many diseases and how our immune system is fighting them. Now, a group of scientists from the University of Rome (Italy) has found a way to repurpose them so that they can trigger specific chemical reactions.
“We showed a strategy for using specific antibodies to control the chemical reactions that form a wide range of molecules from imaging to therapeutic agents,” a full professor and senior author at the University of Rome Tor Vergata Francesco Ricci said. “Our method allows the synthesis of functional molecules from inactive precursors only when specific antibodies are present in the reaction mixture.”
To achieve this goal, the researchers took advantage of the versatility of synthetic DNA oligonucleotides and the predictability of DNA-DNA interactions. “Synthetic oligonucleotides are amazing molecules that can be modified with a series of reactive groups and recognition elements that can target specific antibodies,” said Lorena Baranda, a PhD student in Professor Ricci’s group. “In our work, we reasonably designed and synthesized a pair of modified DNA sequences that can recognize and bind to specific antibodies. When this happens, the reactive group attached to the other end of the DNA chain will be very close. Their reaction will eventually be triggered, leading to the formation of chemical products.”
The strategies demonstrated in this work can be used, for example, to control the formation of functional molecules (such as therapeutic agents) through biomarker antibodies. As a proof of the principle of this possible application, the researchers demonstrated the formation of an anticoagulant that can inhibit the activity of thrombin, which is a key enzyme for blood coagulation and an important target for the treatment of thrombosis. Professor Ricci said: “We proved that a specific IgG antibody can trigger the formation of anticoagulants, which has been further proven to effectively inhibit the activity of thrombin.” This strategy is highly specific to the target antibody and can be programmed. We believe this will become a new approach for targeted therapy and diagnosis. “He concluded.
Reference: “Nature Communications”, written by Lorena Baranda Pellejero, Malihe Mahdifar, Gianfranco Ercolani, Jonathan Watson, Tom Brown Jr and Francesco Ricci, “Using antibodies to control chemical reactions in DNA templates”, December 7, 2020, DOI: 10.1038/s41467 -020-20024 -3
The research in this article was also carried out by Gianfranco Ercolani and Malihe Mahdifar of the University of Tor Vergata in Rome, and Jonathan Watson and Tom Brown Jr of ATDBio, Oxford, UK.
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Post time: Dec-23-2020