Biomedical Engineering Reference
In-Depth Information
CHAPTER 8
Polysaccharide/Polynucleotide
Complexes for Cell-Specific
DNA Delivery
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SHINICHI MOCHIZUKI
a
AND KAZUO SAKURAI*
a,b
a
Department of Chemistry and Biochemistry, The University of Kitakyushu,
1-1, Hibikino, Wakamatsu-ku, Kitakyushu, Fukuoka, 808-0135, Japan;
b
CREST, Japan Science and Technology Agency, 4-1-8, Honcho, Kawaguchi-
shi, Saitama, 332-0012, Japan
*
E-mail: sakurai@kitakyu-u.ac.jp
8.1 Introduction
Recent studies have shown that synthetic oligonucleotides, including antisense,
CpG DNAs, and siRNA, are useful in the treatment of various incurable
diseases. The first generation of antisense oligonucleotides has reached clinical
testing
1-4
in various sites, while many groups propose the second generation
with higher binding affinities, greater stability, and lower toxicity as clinical
candidates.
5-7
However, there are a number of problems to overcome for in vivo
use, such as rapid excretion via the kidneys, degradation in serum, uptake by
phagocytes of the reticuloendothelial system, and inefficient endocytosis by
target cells. In order to put these therapeutic oligonucleotides to practical use,
the development of an efficient drug currier is deemed inevitable.
8-10
A variety of
supramolecular nanocarriers, including liposomes,
11
cationic polymer com-
plexes,
12,13
and various polymeric nanoparticles,
14
have been used to deliver
antisense and siRNA oligonucleotides.
3,15-20
Complexation of oligonucleotides
