Nonviral Gene Delivery by Tetraamino Fullerene

A fullerene derivative bearing two diamino side chains binds to a plasmid vector DNA, either 4 or 40 kbp in size, delivers it to mammalian cells on incubation, and leads to expression of the encoded gene either transiently or stably. The initial physicochemical investigations upon DNA-binding and pr...

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Bibliographic Details
Published in:Molecular pharmaceutics 2006-03, Vol.3 (2), p.124-134
Main Authors: Isobe, Hiroyuki, Nakanishi, Waka, Tomita, Naoki, Jinno, Shigeki, Okayama, Hiroto, Nakamura, Eiichi
Format: Article
Language:English
Subjects:
Animals
Cell Membrane - drug effects
Cercopithecus aethiops
COS Cells
Cytochalasin B - pharmacology
DNA, Viral - genetics
DNA, Viral - metabolism
Drug Delivery Systems - methods
Electrophoresis, Agar Gel
Fullerenes - chemistry
Fullerenes - pharmacology
Genetic Vectors
Molecular Structure
RNA, Viral - genetics
RNA, Viral - metabolism
Transfection - methods
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Summary:A fullerene derivative bearing two diamino side chains binds to a plasmid vector DNA, either 4 or 40 kbp in size, delivers it to mammalian cells on incubation, and leads to expression of the encoded gene either transiently or stably. The initial physicochemical investigations upon DNA-binding and protective properties of various fullerene compounds against nuclease led us to identify the tetraamino fullerene as an ideal candidate to probe the new concept of fullerene-mediated gene delivery to mammalian cells. Studies on transient and stable transfection of COS-1 cells using green fluorescent protein and luciferase reporter genes revealed several useful properties of the fullerene transfection as compared with the conventional lipid-based transfection method, including much higher efficiency of stable transfection and ability to transfect confluent cells. Chemical and biological studies suggested that the cell uptake of the fullerene/DNA complex takes place by an endocytosis mechanism and that the DNA internalized by endosomes is protected by the fullerene against enzymatic digestion. The stiffness of the fullerene/DNA complex may play some role in the success of the fullerene method. Keywords: Fullerene; stable transfection; DNA protection; endocytosis
ISSN:1543-8384
1543-8392
DOI:10.1021/mp050068r