2. Academic Validation
  3. A rationally designed injury kidney targeting peptide library and its application in rescuing acute kidney injury

A rationally designed injury kidney targeting peptide library and its application in rescuing acute kidney injury

  • Sci Adv. 2025 May 2;11(18):eadt3943. doi: 10.1126/sciadv.adt3943.
Yushuo Xiao 1,  Zhijian Tong 1,  Huidie Xu 1,  Zhouyan Jia 1,  Chen Wang 1,  Yang Cao 1,  Liangliang Song 1,  Siyu Hao 1,  Jing Yang 1,  Yihao Zhou 2,  Yunhao Xie 2,  Peng Wu 2,  Tong He 1,  Yancai Wu 1,  Robert B Petersen 3,  Anlin Peng 4,  Chun Zhang 5,  Hong Chen 1,  Ling Zheng 2,  Kun Huang 1 6
Affiliations

Affiliations

  • 1 School of Pharmacy, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Huazhong University of Science and Technology, Wuhan 430030, China.
  • 2 State Key Laboratory of Metabolism and Regulation in Complex Organisms, Hubei Key Laboratory of Cell Homeostasis, Frontier Science Center for Immunology and Metabolism, College of Life Sciences, TaiKang Center for Life and Medical Sciences, Wuhan University, Wuhan 430072, China.
  • 3 Foundational Sciences, Central Michigan University College of Medicine, Mt. Pleasant, MI 48859, USA.
  • 4 Department of Pharmacy, The Third Hospital of Wuhan, Tongren Hospital of Wuhan University, Wuhan 430070, China.
  • 5 Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
  • 6 Tongji-RongCheng Biomedical Center, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
PMID: 40315322 DOI: 10.1126/sciadv.adt3943
Abstract

Acute kidney injury (AKI) has high incidence and mortality rates. Present treatments are mostly symptomatic and cause side effects due to systemic distribution; thus, targeted kidney drug delivery is desired. Transmembrane kidney injury molecule-1 (KIM1) is expressed at low levels in normal kidneys but markedly up-regulated following injury, making it an ideal marker/target for injured kidneys. Here, assisted by AlphaFold, we constructed a library of 1885 peptides that target the extracellular Ig V domain of KIM1 based on interacting fragments from 47 potential KIM1 binding proteins followed by systemic optimization according to their binding energies with KIM1. Experimental validation of top candidates (TKP 1-5) demonstrated that TKP 4 efficiently targeted injured renal cells/kidneys, with its specificity demonstrated in KIM1 knockout cells/mice. TKP 4-decorating liposomes were loaded with nystatin, a renal-protective compound with systemic side effects, and efficiently targeted injured mouse kidneys and alleviated AKI. This work establishes a virtual platform to screen/identify drug delivery candidates with broad research/therapeutic potentials.

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