Development of gene delivery system by using DNA complexes and their application to antisense drug

Toshinori Sato, Y. Okahata

Research output: Contribution to journalArticle

Abstract

Recently, development of delivery system for oligonucleotides and genes into mammalian cells has been remarkably improved. Basic requirements for the therapeutic use of nucleotides are both of increase in their stability and efficient cell uptake. In this paper, we newly prepared DNA complexes with cationic lipoglutamates such as dibutyl glutamate (2C4N+), dihexyl glutamate (2C6N+) and dioctyl glutamate (2C8N+). Formations of the DNA/lipoglutamate complexes were confirmed by gel chromatography, elemental analysis, CD spectra, and light scattering measurement. Compaction of DNA by binding with the cationic lipoglutamate was revealed by means of multi-angle light scattering. The DNA/lipoglutamate complexes showed the increase in the stability against enzymatic hydrolysis by DNase I. The DNA/lipoglutamate complexes showed increase in cell uptake and transfection efficiency (CAT assay). The transfection efficiency of DNA/2C8N+ complex was comparable with that of commercially available lipofectin. Furthermore, a DNA complex with lipoglutamide (2EO4C10N+) having tetraethyleneglycol tails was prepared. This DNA/2EO4C10N+ complex showed high water solubility. And, the complexes of DNA or antisense (S-oligo) with 2EO4C10N+ showed efficient uptake by Hera cells, and showed intracellular distribution to the cytoplasmic reagion.

Original languageEnglish
Pages (from-to)2857-2866
Number of pages10
JournalNippon rinsho. Japanese journal of clinical medicine
Volume54
Issue number10
Publication statusPublished - 1996 Oct
Externally publishedYes

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Gene Transfer Techniques
DNA
Pharmaceutical Preparations
Glutamic Acid
Transfection
Antisense DNA
Light
Deoxyribonuclease I
Therapeutic Uses
Oligonucleotides
Solubility
Gel Chromatography
Spectrum Analysis
Hydrolysis
Nucleotides
Water

Cite this

Development of gene delivery system by using DNA complexes and their application to antisense drug. / Sato, Toshinori; Okahata, Y.

In: Nippon rinsho. Japanese journal of clinical medicine, Vol. 54, No. 10, 10.1996, p. 2857-2866.

Research output: Contribution to journalArticle

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