Therapeutic delivery of siRNA with polymeric carriers to down-regulate STAT5A expression in high-risk B-cell acute lymphoblastic leukemia (B-ALL)

• DOI: 10.1371/journal.pone.0251719
• Publication Date: 2021-06-22T20:02:32Z
• Authors: Mahsa Mohseni; Cezary Kucharski; Remant Bahadur K. C.; Mohammad Nasrullah; Xiaoyan Jiang; Hasan Uludağ; Joseph Brandwein
• Keywords: Trypan blue; STAT5

Overexpression and persistent activation of STAT5 play an important role in the development progression acute lymphoblastic leukemia (ALL), most common pediatric cancer. Small interfering RNA (siRNA)-mediated downregulation represents a promising therapeutic approach for ALL to overcome limitations current treatment modalities such as high relapse rates poor prognosis. However, effectively transport siRNA molecules target cells, potent carriers is utmost importance surpass hurdles delivery. In this study, we investigated use lipopolymers non-viral delivery systems derived from low molecular weight polyethylenimines (PEI) substituted with lauric acid (Lau), linoleic (LA) stearic (StA) deliver cell lines primary samples. Among lipid-substituted polymers explored, Lau- LA-substituted PEI displayed excellent SUP-B15 RS4;11 cells. STAT5A gene expression was downregulated (36–92%) (32%) cells using polymeric systems, which consequently reduced growth inhibited formation colonies With regard siRNA-mediated silencing observed four eight patient our leading system, 1.2PEI-Lau8, accompanied by significant reduction colony three patients. both BCR-ABL positive negative groups, five patients demonstrated marked inhibition MTT trypan blue exclusion assays 1.2PEI-Lau8/siRNA complexes comparison their control groups. Three samples did not show any results systems. Differential responses therapy different could result variable genetic profiles patient-to-patient variability This study supports potential designed system therapy.