The conjugation of diphtheria toxin T domain to poly(ethylenimine) based vectors for enhanced endosomal escape during gene transfection

Shinji Kakimoto, Tsutomu Hamada, Yuuki Komatsu, Masahiro Takagi, Toshizumi Tanabe, Hideki Azuma, Seiji Shinkai, Takeshi Nagasaki

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

The endosomal escape is a well-known serious obstacle for non-viral gene delivery. This is because of an acidic and enzymatic degradation of the contents of the endosome/lysosome. Therefore, the internalized gene needs to be efficient released into the cytosol to obtain the efficiently transfection efficiency. On the other hand, the diphtheria toxin T domain fuses with endosome membrane by pH decrease, then enhances the endosomal escape of the diphtheria toxin C fragment. In this study, we constructed diphtheria toxin T domain-conjugated poly(ethylenimine)s (PEI) polyplex for enhancing the endosomal escape of exogenous gene. The conjugation of diphtheria toxin T domain with PEI/pDNA polyplex leads to the significant enhancement of transfection efficiency when compared with plain PEI/pDNA polyplex. The pH-responsive increase in hydrophobicity of the diphtheria toxin T domain might not only trigger the perturbation of the endocytic vesicle membrane but might also increase the membrane permeability.

Original languageEnglish
Pages (from-to)402-408
Number of pages7
JournalBiomaterials
Volume30
Issue number3
DOIs
Publication statusPublished - Jan 1 2009

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Diphtheria Toxin
Polyetherimides
Transfection
Genes
Membranes
Endosomes
Electric fuses
Hydrophobicity
Transport Vesicles
Degradation
Lysosomes
Hydrophobic and Hydrophilic Interactions
Cytosol
Permeability
aziridine

All Science Journal Classification (ASJC) codes

  • Biomaterials
  • Bioengineering
  • Ceramics and Composites
  • Mechanics of Materials
  • Biophysics

Cite this

The conjugation of diphtheria toxin T domain to poly(ethylenimine) based vectors for enhanced endosomal escape during gene transfection. / Kakimoto, Shinji; Hamada, Tsutomu; Komatsu, Yuuki; Takagi, Masahiro; Tanabe, Toshizumi; Azuma, Hideki; Shinkai, Seiji; Nagasaki, Takeshi.

In: Biomaterials, Vol. 30, No. 3, 01.01.2009, p. 402-408.

Research output: Contribution to journalArticle

Kakimoto, S, Hamada, T, Komatsu, Y, Takagi, M, Tanabe, T, Azuma, H, Shinkai, S & Nagasaki, T 2009, 'The conjugation of diphtheria toxin T domain to poly(ethylenimine) based vectors for enhanced endosomal escape during gene transfection', Biomaterials, vol. 30, no. 3, pp. 402-408. https://doi.org/10.1016/j.biomaterials.2008.09.042
Kakimoto, Shinji ; Hamada, Tsutomu ; Komatsu, Yuuki ; Takagi, Masahiro ; Tanabe, Toshizumi ; Azuma, Hideki ; Shinkai, Seiji ; Nagasaki, Takeshi. / The conjugation of diphtheria toxin T domain to poly(ethylenimine) based vectors for enhanced endosomal escape during gene transfection. In: Biomaterials. 2009 ; Vol. 30, No. 3. pp. 402-408.
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