Creation of Novel Cell-Penetrating Peptides for Intracellular Drug Delivery Using Systematic Phage Display Technology Originated from Tat Transduction Domain

Many biologically active proteins need to be delivered intracellularly to exert their therapeutic action inside the cytoplasm. Cell penetrating peptides (CPPs) have been developed to efficiently deliver a wide variety of cargo in a fully biological active form into a range of cell types for the trea...

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Bibliographic Details
Published in:Biological & Pharmaceutical Bulletin 2007, Vol.30(2), pp.218-223
Main Authors: Kamada, Haruhiko, Okamoto, Takayuki, Kawamura, Maki, Shibata, Hiroko, Abe, Yasuhiro, Ohkawa, Akiko, Nomura, Tetsuya, Sato, Masaki, Mukai, Yohei, Sugita, Toshiki, Imai, Sunao, Nagano, Kazuya, Tsutsumi, Yasuo, Nakagawa, Shinsaku, Mayumi, Tadanori, Tsunoda, Shin-ichi
Format: Article
Language:English
Subjects:
Animals
Bacteriophages
cell penetrating peptide
CHO Cells
Cricetinae
Cricetulus
DNA, Complementary - genetics
Drug Delivery Systems
Endocytosis
Gene Products, tat
HeLa Cells
Humans
Peptide Library
Peptides - genetics
Peptides - metabolism
phage display
Protein Synthesis Inhibitors
Recombinant Fusion Proteins - genetics
Tat
Transduction, Genetic
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Summary:Many biologically active proteins need to be delivered intracellularly to exert their therapeutic action inside the cytoplasm. Cell penetrating peptides (CPPs) have been developed to efficiently deliver a wide variety of cargo in a fully biological active form into a range of cell types for the treatment of multiple preclinical disease models. To further develop this methodology, we established a systematic approach to identify novel CPPs using phage display technology. Firstly, we screened a phage peptide library for peptides that bound to the cell membrane. Secondly, to assess functionality as intracellular carriers, we recombined cDNAs of binding peptides with protein synthesis inhibitory factor (PSIF) to create fusion proteins. Randomly chosen clones were cultured and expression of peptide-PSIF fusion proteins induced, followed by screening of protein synthesis activity in cells. Using this systematic approach, novel and effective CPPs were rapidly identified. We suggest that these novel cell-penetrating peptides can utilized as drug delivery tools for protein therapy or an analytical tool to study mechanisms of protein transduction into the cytoplasm.
ISSN:0918-6158
1347-5215
DOI:10.1248/bpb.30.218