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New technology for optogenetic activation of intracellular antibodies

The immune system defends our body against infection and disease. Antibodies are Y-shaped proteins that play a key role in immune responses. Similar to how powdered sugar dissolves more easily in water than cube sugar, shorter antibody fragments dissolve more easily in cells than longer ones. Due to this characteristic, fragmented antibodies have long been used as materials for biological tools and medicine.

When antibodies are used as direct treatment for diseases, they are refined and introduced into the body. They are activated upon entering, and thus may take effect in unintended areas. Antibody-based immunotherapy has been associated with adverse reactions as antibodies cannot be activated at specific times and in desired body parts. To address this issue, the research team led by Prof. Heo, Won Do developed a novel optogenetic platform called Optobody, which allows control of the optogenetic activation of antibodies.

Optobody technology uses light for direct control of antibody activation

The proposed Optobody (Optogenetically activated intracellular antibody) technology enables fine-tuning of the activation of antibodies using light. By using light as a medium, antibodies can be activated at the desired time and in desired body parts. When split GFP nanobodies in the inactive state are exposed to blue light, they are recombined and activated. The activated antibody fragments suppress the proteins involved in cell movement. The Optobody technology was tested on GFP nanobodies as well as other widely used antibody fragments. In addition, the team developed Chemobody (Chemogenetically activated intracellular antibody), which controls the activation of antibodies using chemical substances. Antibody fragments were recombined with rapamysin and activated, and observations revealed that the proteins involved in cell movement were suppressed by the activated antibody fragments.

New possibilities for the development of antibodies and next-generation immunotherapy

The significance of this study lies in its discovery of the relationship between antibody fragmentation and activation based on optogenetics. Each protein plays a unique role in the human body. The role of a specific protein can be determined by tracking the function that is lost when the protein is suppressed. The activated antibodies can be used as biosensors for monitoring of real-time activation and movement of proteins. Since existing methods of antibody activation control rely on chemical substances, they are only able to induce the expression of antibodies, and do not allow precise control of activation. The proposed optogenetic platform enables quick and precise control of antibody activation using light. As such, it is expected to have various applications in optogenetics and antibody drugs.

Prof. Heo, Won Do
2019 KI Annual Report

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