Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Inhibition of Melanosome Transport by Inducing Exon Skipping in Melanophilin

  • Jin Young Kim (Department of Genetic & Biotechnology, Graduate School of Biotechnology, College of Life Sciences, Kyung Hee University) ;
  • Seon-Young Han (OliPass Cosmeceuticals Company) ;
  • Kiho Sung (OliPass Cosmeceuticals Company) ;
  • Jeong Yeon Seo (OliPass Cosmeceuticals Company) ;
  • Cheol Hwan Myung (Department of Genetic & Biotechnology, Graduate School of Biotechnology, College of Life Sciences, Kyung Hee University) ;
  • Chan Song Jo (Department of Genetic & Biotechnology, Graduate School of Biotechnology, College of Life Sciences, Kyung Hee University) ;
  • Jee Hoe Yoon (Department of Genetic & Biotechnology, Graduate School of Biotechnology, College of Life Sciences, Kyung Hee University) ;
  • Ji Yun Park (Department of Genetic & Biotechnology, Graduate School of Biotechnology, College of Life Sciences, Kyung Hee University) ;
  • Jae Sung Hwang (Department of Genetic & Biotechnology, Graduate School of Biotechnology, College of Life Sciences, Kyung Hee University)
  • Received : 2022.12.19
  • Accepted : 2023.03.02
  • Published : 2023.07.01
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Abstract

Exon skipping is an efficient technique to inhibit specific gene expression induced by a short-sequence peptide nucleic acid (PNA). To date, there has been no study on the effects of PNA on skin pigmentation. In melanocytes, the tripartite complex is responsible for the transport of mature melanosomes from the nucleus to the dendrites. The tripartite complex is composed of Rab27a, Mlph (Melanophilin), and Myosin Va. Defects in the protein Mlph, a melanosome transport-related protein, are known to cause hypopigmentation. Our study shows that Olipass peptide nucleic acid (OPNA), a cell membrane-permeable PNA, targets exon skipping in the Mlph SHD domain, which is involved in Rab27a binding. Our findings demonstrate that OPNA induced exon skipping in melan-a cells, resulting in shortened Mlph mRNA, reduced Mlph protein levels, and melanosome aggregation, as observed by microscopy. Therefore, OPNA inhibits the expression of Mlph by inducing exon skipping within the gene. These results suggest that OPNA, which targets Mlph, may be a potential new whitening agent to inhibit melanosome movement.

Keywords

Acknowledgement

This work was supported by the Technology development Program (S2680942) funded by the Ministry of SMEs and Startups (MSS, Korea).

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