Biological and Pharmaceutical Bulletin
Online ISSN : 1347-5215
Print ISSN : 0918-6158
ISSN-L : 0918-6158
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Creation of Novel Cell-Penetrating Peptides for Intracellular Drug Delivery Using Systematic Phage Display Technology Originated from Tat Transduction Domain
Haruhiko KamadaTakayuki OkamotoMaki KawamuraHiroko ShibataYasuhiro AbeAkiko OhkawaTetsuya NomuraMasaki SatoYohei MukaiToshiki SugitaSunao ImaiKazuya NaganoYasuo TsutsumiShinsaku NakagawaTadanori MayumiShin-ichi Tsunoda
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2007 年 30 巻 2 号 p. 218-223

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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.

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© 2007 The Pharmaceutical Society of Japan
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