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An overview of strategies and challenges adopted to silence BCR-ABL gene by small interfering RNA.

Laura Fancello,M. Manconi,M. Manca

Published 2025 in Nanomedicine

ABSTRACT

BCR-ABL oncogene associated with chronic myeloid leukemia (CML) encodes for tyrosine kinase with enhanced activity that drives the uncontrolled proliferation of white blood cells. The therapy with tyrosine kinase inhibitors improves the life expectancy of patients without curative effects. However, lifelong treatments are required and usually associated with adverse effects and drug resistance. Alternatively, gene-silencing using nucleic acids has been proposed to avoid the synthesis of protein kinase. The use of RNA Interference seems to be the most promising strategy for new therapy. This review provides an overview of clinically used therapy with tyrosine kinase inhibitors and explores future advances using RNA interference, especially siRNA, as it is the one tested the most up to now. The studies reporting the use of siRNA to silence BCR-ABL gene are analyzed based on the used sequence, chemical modifications, and delivery systems. The sequence that targets specific regions of BCR-ABL gene and chemical modifications that improve stability, specificity, and potency are underlined. Finally, the studies devoted to delivering siRNA have been examined based on the vector nature (natural or synthetic) and delivery mechanism (conjugation or loading). The level of maturity reached (in vitro, in vivo, pre-clinical) in the studies has been underlined. No clinical studies were found.

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