6 Aptamers for Targeted Therapy
155
6.5.2 Aptamer as Inhibitor
6.5.2.1 AS1411 Targeting Nucleolin
Nucleolin is one of the most abundant non-ribosomal phosphoproteins in nucleolus
[192]. The expression of nucleolin in rapidly proliferating cells is much higher than
that in normal cells and is related to the increased malignant degree of cancer [193,
194]. Therefore, nucleolar proteins are considered as potential targets for the diagnosis and treatment of cancer. AS1411 (5
-GGT GGT GGG GGG TTG TGG GTG
GGG TGG GGG GG-3
) is a 26 nt DNA aptamer with G-quadruplex structure and
can bind to nucleolin, which was accidentally identified by Bates et al. [195] during
the study on the regulation of cancer gene expression by oligonucleic acid triplex.
AS1411 exhibits growth inhibition on a wide range of cancer cell lines and is used
as a therapeutic agent and targeted ligand in a variety of cancer therapeutic studies
(Fig. 6.11).
The AS1411 sequence is rich in guanine and forms G-quadruplex structures of
various monomers and dimers in physiological buffers in vitro. It is the most widely
used aptamer in cancer therapy. In 2003, AS1411 entered the phase 1 clinical trials.
Aptamera company named AS1411 AGRO100. AS1411 in 17 patients with advanced
cancer showed very good tolerance, 7 days infusion dose up to 40 mg/kg/day, and
no serious side effects were observed. In 2005, Antisoma acquired Aptamera and
Fig. 6.11 Applications and advantages of AS1411 as a tumor targeting agent [196]
155
6.5.2 Aptamer as Inhibitor
6.5.2.1 AS1411 Targeting Nucleolin
Nucleolin is one of the most abundant non-ribosomal phosphoproteins in nucleolus
[192]. The expression of nucleolin in rapidly proliferating cells is much higher than
that in normal cells and is related to the increased malignant degree of cancer [193,
194]. Therefore, nucleolar proteins are considered as potential targets for the diagnosis and treatment of cancer. AS1411 (5
-GGT GGT GGG GGG TTG TGG GTG
GGG TGG GGG GG-3
) is a 26 nt DNA aptamer with G-quadruplex structure and
can bind to nucleolin, which was accidentally identified by Bates et al. [195] during
the study on the regulation of cancer gene expression by oligonucleic acid triplex.
AS1411 exhibits growth inhibition on a wide range of cancer cell lines and is used
as a therapeutic agent and targeted ligand in a variety of cancer therapeutic studies
(Fig. 6.11).
The AS1411 sequence is rich in guanine and forms G-quadruplex structures of
various monomers and dimers in physiological buffers in vitro. It is the most widely
used aptamer in cancer therapy. In 2003, AS1411 entered the phase 1 clinical trials.
Aptamera company named AS1411 AGRO100. AS1411 in 17 patients with advanced
cancer showed very good tolerance, 7 days infusion dose up to 40 mg/kg/day, and
no serious side effects were observed. In 2005, Antisoma acquired Aptamera and
Fig. 6.11 Applications and advantages of AS1411 as a tumor targeting agent [196]