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Development of Organelle Replacement Therapy Using a Stearyl-Polyhistidine Peptide against Lysosomal Storage Disease Cells.
Hayashi, Taiki; Okamoto, Riku; Kawano, Tsuyoshi; Iwasaki, Takashi.
Afiliação
  • Hayashi T; Department of Agricultural Science, Graduate School of Sustainability Science, Tottori University, Tottori 680-8553, Japan.
  • Okamoto R; Department of Bioresources Science, Faculty of Agriculture, Tottori University, Tottori 680-8553, Japan.
  • Kawano T; Department of Agricultural Science, Graduate School of Sustainability Science, Tottori University, Tottori 680-8553, Japan.
  • Iwasaki T; Department of Agricultural Science, Graduate School of Sustainability Science, Tottori University, Tottori 680-8553, Japan. itaka@tottori-u.ac.jp.
Molecules ; 24(16)2019 Aug 18.
Article em En | MEDLINE | ID: mdl-31426598
We previously reported on a polyhistidine peptide, His16 peptide, as a new cell-penetrating peptide. This peptide is anticipated to be a new carrier for drug delivery systems (DDSs) for targeting intracellular lysosomes because it can transport macromolecules (e.g., liposomes) into these organelles. In the present study, we examined the application of His16 peptide as a DDS carrier against lysosomal storage disease (LSD) cells. LSDs are metabolic disorders caused by loss of specific lysosomal enzymes. For the treatment of LSD cells, we devised a system designated organelle replacement therapy (ORT). ORT is a strategy for transporting exogenous lysosomes containing all kinds of lysosomal enzymes from normal cells into endogenous lysosomes in LSD cells using His16 peptide. To develop the ORT system, we prepared His16 peptide-modified healthy lysosomes (His16-Lyso) by insertion of a stearyl-His16 peptide into a hydrophobic region in the lysosomal membrane. His16-Lyso showed cellular uptake and localization to endogenous lysosomes in LSD cells. His16-Lyso also restored the proliferation of LSD cells, which otherwise showed slower proliferation than normal cells. These results suggested that His16-Lyso replenished deficient lysosomal enzymes in LSD cells. The results further suggest that His16-Lyso are promising candidates as a treatment tool for LSD cells and to establish a foundation for ORT.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Portadores de Fármacos / Peptídeos Penetradores de Células / Engenharia Celular / Histidina / Lisossomos Limite: Humans Idioma: En Ano de publicação: 2019 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Portadores de Fármacos / Peptídeos Penetradores de Células / Engenharia Celular / Histidina / Lisossomos Limite: Humans Idioma: En Ano de publicação: 2019 Tipo de documento: Article