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. 2021 May 10;60(20):11267-11271.
doi: 10.1002/anie.202102170. Epub 2021 Apr 7.

Bispecific Aptamer Chimeras Enable Targeted Protein Degradation on Cell Membranes

Yanyan Miao  1 , Qianqian Gao  1 , Menghan Mao  1 , Chao Zhang  1 , Liqun Yang  1 , Yang Yang  2 , Da Han  1
Affiliations

Bispecific Aptamer Chimeras Enable Targeted Protein Degradation on Cell Membranes

Yanyan Miao et al. Angew Chem Int Ed Engl. .

Abstract

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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References

    1. M. Uhlen, L. Fagerberg, B. M. Hallstrom, C. Lindskog, P. Oksvold, A. Mardinoglu, A. Sivertsson, C. Kampf, E. Sjostedt, A. Asplund, I. Olsson, K. Edlund, E. Lundberg, S. Navani, C. A. Szigyarto, J. Odeberg, D. Djureinovic, J. O. Takanen, S. Hober, T. Alm, P. H. Edqvist, H. Berling, H. Tegel, J. Mulder, J. Rockberg, P. Nilsson, J. M. Schwenk, M. Hamsten, K. von Feilitzen, M. Forsberg, L. Persson, F. Johansson, M. Zwahlen, G. von Heijne, J. Nielsen, F. Ponten, Science 2015, 347, 1260419.
    1. H. Yin, A. D. Flynn, Annu. Rev. Biomed. Eng. 2016, 18, 51-76.
    1. A. Christopoulos, Nat. Rev. Drug Discovery 2002, 1, 198-210.
    1. S. Tomoshige, M. Ishikawa, Angew. Chem. Int. Ed. 2021, 60, 3346-3354.
    1. R. L. Setten, J. J. Rossi, S. P. Han, Nat. Rev. Drug Discovery 2019, 18, 421-446.

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