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Mol. Cells 2012; 34(6): 577-583

Published online December 13, 2012

https://doi.org/10.1007/s10059-012-0284-y

© The Korean Society for Molecular and Cellular Biology

Identification of a Novel Cell-Penetrating Peptide from Human Phosphatidate Phosphatase LPIN3

Sangho Lim1,2, Won-ju Kim1,2, Yeon-ho Kim1,2, and Je-Min Choi1,2,*

1Department of Life Science, Research Institute for Natural Sciences, Hanyang University, Seoul 133-791, Korea, 2Hanyang Biomedical Research Institute, Hanyang University, Seoul 133-791, Korea

Correspondence to : *Correspondence: jeminchoi@hanyang.ac.kr

Received: November 1, 2012; Revised: November 19, 2012; Accepted: November 20, 2012

Abstract

Biomolecules such as proteins, DNA, and RNA are mac-romolecules and can not cross the cell membrane. How-ever, cell-penetrating peptide (CPP) has been shown to deliver therapeutic biomolecules successfully into cells. The various and widely used CPPs including TAT, VP22, and Antp are mostly non-human originated CPPs, and are limited by their potential toxicity and immunogenicity. We report here on a newly identified novel cell-penetrating sequence (LPIN; RRKRRRRRK) from the nuclear localization sequence (NLS) of human nuclear phosphatase, LPIN3. LPIN-EGFP recombinant protein was concentration- and time-dependently delivered into cells and localized to the nucleus as well as the cytoplasm. It penetrated the cell membrane by lipid raft-mediated endocytosis by binding to heparan sulfate proteoglycan. LPIN-EGFP was successfully delivered into primary mouse splenocytes in vitro and it could be delivered into various tissues including liver, kidney, and intestine in mice after intra-peritoneal injection. This re-search suggests that LPIN-CPP could be used in a drug delivery system to deliver therapeutic biomolecules including peptides, proteins, DNA, and RNA and without the limitations of non-human originated CPPs such as TAT-CPP.

Keywords CPP, drug delivery system, LPIN, PTD

Article

Research Article

Mol. Cells 2012; 34(6): 577-583

Published online December 31, 2012 https://doi.org/10.1007/s10059-012-0284-y

Copyright © The Korean Society for Molecular and Cellular Biology.

Identification of a Novel Cell-Penetrating Peptide from Human Phosphatidate Phosphatase LPIN3

Sangho Lim1,2, Won-ju Kim1,2, Yeon-ho Kim1,2, and Je-Min Choi1,2,*

1Department of Life Science, Research Institute for Natural Sciences, Hanyang University, Seoul 133-791, Korea, 2Hanyang Biomedical Research Institute, Hanyang University, Seoul 133-791, Korea

Correspondence to:*Correspondence: jeminchoi@hanyang.ac.kr

Received: November 1, 2012; Revised: November 19, 2012; Accepted: November 20, 2012

Abstract

Biomolecules such as proteins, DNA, and RNA are mac-romolecules and can not cross the cell membrane. How-ever, cell-penetrating peptide (CPP) has been shown to deliver therapeutic biomolecules successfully into cells. The various and widely used CPPs including TAT, VP22, and Antp are mostly non-human originated CPPs, and are limited by their potential toxicity and immunogenicity. We report here on a newly identified novel cell-penetrating sequence (LPIN; RRKRRRRRK) from the nuclear localization sequence (NLS) of human nuclear phosphatase, LPIN3. LPIN-EGFP recombinant protein was concentration- and time-dependently delivered into cells and localized to the nucleus as well as the cytoplasm. It penetrated the cell membrane by lipid raft-mediated endocytosis by binding to heparan sulfate proteoglycan. LPIN-EGFP was successfully delivered into primary mouse splenocytes in vitro and it could be delivered into various tissues including liver, kidney, and intestine in mice after intra-peritoneal injection. This re-search suggests that LPIN-CPP could be used in a drug delivery system to deliver therapeutic biomolecules including peptides, proteins, DNA, and RNA and without the limitations of non-human originated CPPs such as TAT-CPP.

Keywords: CPP, drug delivery system, LPIN, PTD

Mol. Cells
Jan 31, 2023 Vol.46 No.1, pp. 1~67
COVER PICTURE
RNAs form diverse shapes and play multiple functions as central molecules of gene expression. In this special issue on RNA, seven minireviews illustrate how basic concepts and recent RNA biology findings are transformed into new and exciting RNA therapeutics.

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