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ePoster Display

30P - Targeting of BCR-ABL gene expression in K562 cells using cell-penetrating peptide nanocomplexes carrying siRNAs


16 Sep 2021


ePoster Display


Basic Science

Tumour Site


Vera Vysochinskaya


Annals of Oncology (2021) 32 (suppl_5): S361-S375. 10.1016/annonc/annonc684


V. Vysochinskaya1, N.A. Knyazev2, A. Emelyanov2, I. Terterov2, V. Klimenko2, A.A. Bogdanov2, M. Dubina3

Author affiliations

  • 1 Department Of Molecular Biology Of Viruses, Smorodintsev Research Institute of Influenza, Ministry of Health of the Russian Federation, 197376 - Saint-Petersburg/RU
  • 2 Scientific Department, St. Petersburg Clinical Research and Practical Center of Specialized Types of Medical Care (Oncologic), 197758 - Saint-Petersburg/RU
  • 3 Director Executive, State Research Institute of Highly Pure Biopreparations, 197110 - Saint-Petersburg/RU


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Abstract 30P


Gene silencing by small interfering RNA (siRNA) is a promising therapeutic approach for a wide range of disorders, including cancer. siRNAs against BCR-ABL can be a supportive or alternative measure to traditional chronic myeloid leukemia (CML) tyrosine kinase inhibitors (TKIs) therapies, especially given frequently-noted clinical TKI resistance. The main challenge for such approaches remains the development of effective RNAi systems for intracellular delivery. Cell-penetrating peptides (CPPs) are oligopeptides which have the ability to deliver various cargo molecules. They represent a promising approach of achieving siRNA internalization. Despite the active research mechanisms through which CPPs are internalized remain unclear. It has already been shown that CPPs and their cargoes can be taken up by cells via single or multiple endocytic pathways. Precise siRNA delivery mechanism seems to depend on experimental conditions. In present study we investigated cellular uptake efficiency, internalization mechanism and gene-silencing efficiency of a non-covalent nanocomplex consisting of CPP peptide EB1 and siRNA directed against the BCR-ABL oncogene in the K562 human CML cell line.


The transfection efficiency of the investigated peptide EB1-BCR-ABL siRNA complexes was measured by flow cytometry analysis. In order to study the complex’s internalization mechanisms, transfection was carried out at 4 °C and was analyzed by flow cytometry and confocal microscopy. RNAi modulatory effects were investigated on both mRNA and protein levels of the BCR-ABL using RT-PCR and Western blotting.


We have shown that the transfection efficiency of the investigated complexes was greater than 90%. It was demonstrated that complexes effectively deliver siRNA into K562 cells by endocytic mechanisms. Thereby, transfection of K562 cells by the peptide complexes significantly reduced the levels of BCR-ABL mRNA, with a maximum at 72 h post treatment. Similar decreases in BCR-ABL protein were detected.


Obtained data indicates that CCP-based delivery of siRNAs enables an effective antisense suppression of certain oncogene and represents a promising new class of therapies for CML.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.


Has not received any funding.


All authors have declared no conflicts of interest.

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