Enhancement of anti-tumor activity in melanoma using arginine deiminase fused with 30Kc19α protein

Lee, Haein; Park, Geunhwa; Kim, Seulha; Son, Boram; Joo, Jinmyoung; Park, Hee Ho; Park, Tai Hyun

doi:10.1007/s00253-022-12218-0

Cited by 1 publication

(1 citation statement)

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“…Previous studies have demonstrated that fusion with 30Kc19 delivers non-permeable proteins in various mammalian cells and improves the stability of fusion partner proteins ( Lee et al, 2019 ; Lee J et al, 2020 ; Kim et al, 2022 ; Son et al, 2022 ). Additionally, 30Kc19α retains the cell-penetrating and protein-stabilizing properties of the full-length 30Kc19 ( Ryu et al, 2016 ; Lee H et al, 2020 ; Lee et al, 2022 ). Our results indicate that the 30Kc19α–Lin28A fusion protein can be delivered into USCs without any significant cytotoxicity, increasing their osteogenic differentiation.…”

Section: Introductionmentioning

confidence: 99%

Enhanced osteogenesis of human urine-derived stem cells by direct delivery of 30Kc19α–Lin28A protein

Park

Jeong

Kim

et al. 2023

Front. Bioeng. Biotechnol.

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Urine-derived stem cells (USCs) are a promising source for regenerative medicine because of their advantages such as easy and non-invasive collection from the human body, stable expansion, and the potential to differentiate into multiple lineages, including osteoblasts. In this study, we propose a strategy to enhance the osteogenic potential of human USCs using Lin28A, a transcription factor that inhibits let-7 miRNA processing. To address concerns regarding the safety of foreign gene integration and potential risk of tumorigenicity, we intracellularly delivered Lin28A as a recombinant protein fused with a cell-penetrating and protein-stabilizing protein, 30Kc19α. 30Kc19α–Lin28A fusion protein exhibited improved thermal stability and was delivered into USCs without significant cytotoxicity. 30Kc19α–Lin28A treatment elevated calcium deposition and upregulated several osteoblast-specific gene expressions in USCs derived from multiple donors. Our results indicate that intracellularly delivered 30Kc19α–Lin28A enhances the osteoblastic differentiation of human USCs by affecting the transcriptional regulatory network involved in metabolic reprogramming and stem cell potency. Therefore, 30Kc19α–Lin28A may provide a technical advancement toward developing clinically feasible strategies for bone regeneration.

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