Gene and Cell Therapy: Biology and Applications by Unknown

Author:Unknown
Language: eng
Format: epub
ISBN: 9789811304811
Publisher: Springer Singapore

AS1411-Nucleolin Aptamer

AS1411 is a G-quadruplex 26-mer DNA aptamer. AS1411 targets the protein nucleolin [15] which plays essential part in cell growth and death through its association in rRNA transport and DNA replication, transcription, and recombination [283]. Nucleolin, a protein that resides in the nucleus and cytoplasm in normal cells, is found to be overexpressed in the plasma membrane in several types of cancer, including breast cancer, lung cancer, prostate cancer, hepatocellular carcinoma, and lymphocytic leukemia [348]. AGRO100, though being developed at Aptamera, was renamed as AS1411 after procurement by Antisoma. In May 2011, AS1411 was further acquired by Advanced Cancer Therapeutics (ACT) and later regarded as ACT-GRO-777. AS1411 inhibits the proliferation of extensive range of cancer cell lines by potentially disrupting the interaction of nucleolin with its binding partners. Cancer cell death induced by AS1411 has been anticipated to include aptamer internalization through membrane or cell surface nucleolin followed by interference with DNA replication leading to S-phase arrest and by the stabilization of the mRNA of B-cell lymphoma protein 2 (BCL-2) [15, 348]. AS1411 exhibits minimal toxicity in patients with progressive solid tumors [134] and is currently in phase II clinical trials for both acute myeloid leukemia (AML) and metastatic renal cell cancer [348].

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