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Development of PRL-3 Specific Nanobodies, PLOS One (2023)


Phosphatase of Regenerating Liver-3 (PRL-3) is associated with the progression and spread of cancer, but the limited number of research tools available to study this protein have prevented us from fully understanding of PRL-3’s role in cancer. To address this, we developed nanobodies, or single-domain antibodies derived from alpacas, that specifically target PRL-3.

Our PRL-3 nanobodies have proven highly effective, with a strong binding affinity to PRL-3 and no activity towards similar proteins. We found that the nanobodies performed better than commercially available antibodies in techniques like immunofluorescence and immunoprecipitation.  Structural analyses showed that the nanobodies partially bind to the active site of PRL-3, interfering with its phosphatase activity. They can also disrupt the interaction between PRL-3 and another protein called CNNM3, which is implicated in promoting cancer metastasis.

These nanobodies represent an expansion of the research tools available to study PRL-3 and are poised to advance our understanding of its role in cancer progression. Nanobodies offer unique benefits, including high specificity, stability, and the ability to penetrate tissues, making them valuable tools for studying target proteins and developing future cancer therapies. By blocking the interaction between PRL-3 and CNNM3, our nanobodies hold promise in combating metastatic cancer growth. Their development opens doors to defining PRL-3’s significance in cancer and possibly targeting it in a clinical setting.

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