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A cell-based single-stranded DNA aptamer specifically targets gastric cancer
Abstract:
Gastric cancer is one of the most prevailing cancers with high morbidity and mortality. Limitations in the current diagnosis and therapy, specially lacking of specific molecular therapeutic targets, ask for the development of new strategies. Aptamer, a newly developed adaptive molecule, could be used in clinical detection and therapy because of its high affinity and specificity. As no aptamer has ever been developed in preventing gastric cancer so far, we were the first who cloned such an aptamer specifically targeting gastric cancer. The aptamer was selected by systematic evolution of ligands by exponential enrichment with gastric cancer cell-line HGC-27 as target cell line and immortalized gastric epithelial cell-line GES-1 as control cell line. The affinity and specificity of candidate aptamers were examined by flow cytometry, confocal imagining and aptamer-based histochemistry staining. After 19 cycles of systematic evolution of ligands by exponential enrichment and subsequent cloning and sequencing, an aptamer with the highest affinity and specificity (nominated as AGC03) among candidates was screened out from a random single-stranded DNA pool. Moreover, AGC03 could not only specifically bind to gastric cancer cells (the equilibrium dissociation constant value was 16.49 ± 0.40 nM) in vitro, but also recognize cancer cells in human cancer tissue. Our most important finding is that AGC03 could even be internalized into cells automatically. In conclusion, we obtained a novel aptamer specifically targeting gastric cancer,which is an effective tool for both gastric cancer diagnosis and drug delivery.
Insights
Researchers developed a novel DNA aptamer (AGC03) targeting gastric cancer cells. This aptamer shows high specificity and affinity, enabling potential applications in gastric cancer diagnosis and targeted drug delivery.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Gastric cancer presents significant global health challenges due to high morbidity and mortality.
- Current diagnostic and therapeutic strategies for gastric cancer are limited by a lack of specific molecular targets.
- Aptamers, as novel DNA molecules, offer potential for targeted diagnostics and therapeutics owing to their specificity and affinity.
Purpose of the Study:
- To develop and characterize a novel aptamer for specific targeting of gastric cancer.
- To evaluate the diagnostic and therapeutic potential of the identified aptamer.
Main Methods:
- Systematic evolution of ligands by exponential enrichment (SELEX) was employed using gastric cancer cells (HGC-27) and normal gastric epithelial cells (GES-1).
- Candidate aptamers were screened for affinity and specificity using flow cytometry, confocal imaging, and aptamer-based histochemistry.
- The selected aptamer (AGC03) was characterized for its binding affinity (Kd) and cellular internalization capabilities.
Main Results:
- A highly specific DNA aptamer, AGC03, was identified after 19 SELEX cycles.
- AGC03 demonstrated high affinity for gastric cancer cells in vitro (Kd = 16.49 ± 0.40 nM) and recognized cancer cells in human tissues.
- Crucially, AGC03 was observed to be internalized into cells autonomously.
Conclusions:
- A novel aptamer, AGC03, specifically targeting gastric cancer has been successfully developed.
- AGC03 represents a promising tool for both the diagnosis of gastric cancer and targeted drug delivery applications.
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