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2015 ; 25
(3
): 162-72
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Identification of epithelial ovarian tumor-specific aptamers
#MMPMID25894736
Benedetto G
; Hamp TJ
; Wesselman PJ
; Richardson C
Nucleic Acid Ther
2015[Jun]; 25
(3
): 162-72
PMID25894736
show ga
Ovarian cancer is often diagnosed in late stages with few treatment options and
poor long-term prognosis. New clinical tools for early detection of ovarian
malignancies will significantly help reduce mortality and improve current
long-term survival rates. The objective of this work was to identify ovarian
tumor-specific single-stranded DNA aptamers that bind to malignant ovarian tumor
cells and internalize with high affinity and specificity. Aptamers can identify
unique tumor biomarkers, can aid in early detection and diagnosis of neoplastic
disorders, and can be functionalized by conjugation to small molecules. To
identify aptamers from random single-stranded DNA pools (60 bases long), we used
whole Cell-SELEX (systematic evolution of ligands by exponential enrichment) to
enrich and isolate tumor-specific aptamers that bind to tumor-specific receptors
in their native state on the cell surface. Next-Generation sequencing identified
seven novel aptamers and detailed analyses of three are described. Aptamers bound
to, and were internalized by, target Caov-3 cell populations, but not nontarget
nonmalignant ovarian epithelial HOSE 6-3 cells or multiple other epithelial tumor
cell lines. Furthermore, aptamers showed unique binding affinities with apparent
dissociation constants (Kd) measuring in the submicromolar range supporting their
physiological relevance and potential use in clinical applications.
|Aptamers, Nucleotide/*genetics
[MESH]
|Carcinoma, Ovarian Epithelial
[MESH]
|Cell Line, Tumor
[MESH]
|Female
[MESH]
|Humans
[MESH]
|Neoplasms, Glandular and Epithelial/*genetics/pathology
[MESH]