The ability to regulate membrane protein abundance offers great opportunities for developing therapeutic sites for various diseases. Herein, we describe a platform for the targeted degradation of membrane-associated proteins using bispecific aptamer chimeras that bind both the cell-surface lysosome-shuttling receptor (IGFIIR) and the targeted membrane-bound proteins of interest. We demonstrate that the aptamer chimeras can efficiently and quickly shuttle the therapeutically relevant membrane proteins of Met and PTK-7 to lysosomes and degrade them through the lysosomal protein degradation machinery. We anticipate that our method will provide a universal platform for the use of readily synthesized aptamer materials for biochemical research and potential therapeutics.
Keywords: aptamers; membrane-associated proteins; protein degradation; receptors; therapeutic strategies.
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