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Nano/Micro Biotechnology pp 197–230Cite as

A Novel Nonviral Gene Delivery System: Multifunctional Envelope-Type Nano Device

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Part of the book series: Advances in Biochemical Engineering / Biotechnology ((ABE,volume 119))

Abstract

In this review we introduce a new concept for developing a nonviral gene delivery system which we call “Programmed Packaging.” Based on this concept, we succeeded in developing a multifunctional envelope-type nano device (MEND), which exerts high transfection activities equivalent to those of an adenovirus in a dividing cell. The use of MEND has been extended to in vivo applications. PEG/peptide/DOPE ternary conjugate (PPD)-MEND, a new in vivo gene delivery system for the targeting of tumor cells that dissociates surface-modified PEG in tumor tissue by matrix metalloproteinase (MMP) and exerts significant transfection activities, was developed. In parallel with the development of MEND, a quantitative gene delivery system, Confocal Image-assisted 3-dimensionally integrated quantification (CIDIQ), also was developed. This method identified the rate-limiting step of the nonviral gene delivery system by comparing it with adenoviral-mediated gene delivery. The results of this analysis provide a new direction for the development of rational nonviral gene delivery systems.

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Abbreviations

Bmpr1a:

Bone morphogenetic protein receptor type 1A

BSA:

Bovine serum albumin

CAR:

Coxsackie and adenovirus receptor

CDAN:

N-Cholesteryloxycarbonyl-3,7-diazanonane-1,9-diamine

CHEMS:

Cholesteryl hemisuccinate

Chol:

Cholesterol

CIDIQ:

Confocal image-assisted three-dimensionally integrated quantification

CLSM:

Confocal laser scanning microscopy

DLinDMA:

1,2-Dilinoleyloxy-N,N-dimethyl-3-aminopropane

DOPE:

Dioleoylphosphatidylethanolamine

DOTAP:

N-[1-(2,3-Dioleoyloxy)propyl]-N,N,N-trimethylammonium chloride

DOTMA:

N-[1-(2,3-Dioleoyloxy)propyl]-N,N,N,-trimethylammonium chloride

ECM:

Extracellular matrix

EPC:

Egg phosphatidylcholine

EPR:

Enhanced permeability and retention

GFP:

Green fluorescent protein

HFs:

Hair follicles

LA2000:

Lipofectamine2000

LFN:

Lipofectamine PLUS

LPD:

Liposome–polycation–DNA lipoplex

MEND:

Multifunctional envelope-type nano device

MMP:

Matrix metalloproteinase

NLS:

Nuclear localization signals

N/P:

Nitrogen/phosphate

ODN:

Oligodeoxynucleotides

ODN-MEND:

R8-MEND-encapsulated ODN

pDNA:

Plasmid DNA

PEG:

Polyethyleneglycol

PEG-MEND:

MEND modified with conventional PEG-lipid

PEI:

Polyethyleneimine

PLL:

Poly-l-lysine

PPD:

PEG/peptide/DOPE ternary conjugate

PPD-MEND:

MEND modified with PPD

PTN:

Pleiotrophin

R8:

Octaarginine

R8-MEND:

MEND modified with high density R8 peptide

RES:

Reticuloendothelial system

RISC:

RNA-induced silencing complex

RNAi:

RNA interference

SAINT-2:

N-Methyl-4(dioleyl)methylpyridiniumchloride

siRNA:

Short interfering RNA

SPLP:

Stabilized plasmid-lipid particle

SUV*:

Small, detergent-rich liposomes

Tf:

Transferrin

Tf-L:

Tf-modified liposomes

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Acknowledgments

This study was performed through Special Coordination Funds for Promoting Science and Technology of the Ministry of Education, Culture, Sports, Science and Technology, the Japanese Government. The authors also wish to thank Dr. James L. McDonald for his helpful advice in writing the English manuscript.

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Authors and Affiliations

  1. Faculty of Pharmaceutical Sciences, Hokkaido University, Kita 12 Nishi 6, Sapporo City, Hokkaido, 060-0812, Japan

    Hiroto Hatakeyama, Hidetaka Akita & Hideyoshi Harashima

  2. Kyoto Pharmaceutical University, 5 Nakauchi-cho, Misasagi, Yamashina-ku, Kyoto, 607-8414, Japan

    Kentaro Kogure

Authors
  1. Hiroto Hatakeyama
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  2. Hidetaka Akita
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  3. Kentaro Kogure
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  4. Hideyoshi Harashima
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Corresponding author

Correspondence to Hideyoshi Harashima .

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Editors and Affiliations

  1. Saitama Industrial Technology Center, Kamiaoki 3-12-18, Kawaguchi-shi, Saitama, 333-0844, Japan

    Isao Endo

  2. School of Engineering, Dept. Bioengineering, University of Tokyo, Hongo 7-3-1, Tokyo, 113-8656, Japan

    Teruyuki Nagamune

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Hatakeyama, H., Akita, H., Kogure, K., Harashima, H. (2009). A Novel Nonviral Gene Delivery System: Multifunctional Envelope-Type Nano Device. In: Endo, I., Nagamune, T. (eds) Nano/Micro Biotechnology. Advances in Biochemical Engineering / Biotechnology, vol 119. Springer, Berlin, Heidelberg. https://doi.org/10.1007/10_2008_40

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