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Parfejevs, V.

Publications and source records attributed to Parfejevs, V..

2 recordsLinked to original sources

Targeting triple-negative breast cancer with β1-integrin binding aptamer

Targeted therapies have increased the treatment options for triple-negative breast cancer patients. However, the paucity of targetable biomarkers and tumour heterogeneity have limited the ability of precision-guided interventions to live up to their full potential. As affinity targeting ligands, aptamers show high selectivity towards target molecules. Compared to antibodies, aptamers have lower molecular weight, increased stability during transportation, reduced immunogenicity, and increased tissue uptake. Recently, we reported the discovery of GreenB1 aptamer that is internalized in cultured triple-negative MDA-MB-231 human breast cancer cells. We show that the GreenB1 aptamer specifically targets {beta}1-integrin, a protein previously linked to breast cancer cell invasiveness and migration. Aptamer binds to {beta}1-integrin with low nanomolar affinity. GreenB1 homes in the orthotopic 4T1 triple-negative breast cancer lesions modelled in mice. Our findings suggest potential applications for the GreenB1-guided precision agents for the diagnosis and therapy of triple-negative breast cancer.

molecular biology↗

Differential binding cell-SELEX: method for identification of cell specific aptamers using high throughput sequencing

Aptamers have evolved as a viable alternative to antibodies in recent years. High throughput sequencing (HTS) has revolutionized the aptamer research by increasing the number of reads from few using Sanger sequencing to millions of reads using HTS approach. Despite the availability and advantages of HTS compared to Sanger sequencing there are only 50 aptamer HTS sequencing samples available on public databases. HTS data for aptamer research are mostly used to compare sequence enrichment between subsequent selection cycles. This approach does not take full advantage of HTS because enrichment of sequences during selection can be due to inefficient negative selection when using live cells. Here we present differential binding cell-SELEX (systematic evolution of ligands by exponential enrichment) workflow that adapts FASTAptamer toolbox and bioinformatics tool edgeR that is mainly used for functional genomics to achieve more informative metrics about the selection process. We propose fast and practical high throughput aptamer identification method to be used with cell-SELEX technique to increase successful aptamer selection rate against live cells. The feasibility of our approach is demonstrated by performing aptamer selection against clear cell renal cell carcinoma (ccRCC) RCC-MF cell line using RC-124 cell line from healthy kidney tissue for negative selection.

molecular biology↗