Evidence map›Paper›PMID 34157051›Full record

ArticlePloS one2021

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

Mahsa Mohseni, Cezary Kucharski, Remant Bahadur K C, Mohammad Nasrullah, Xiaoyan Jiang, Hasan Uludağ, Joseph Brandwein

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in PloS one, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
0.8field-weighted citation impact, top 29% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed, 12 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 1 country.

Mahsa MohseniDepartment of Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada.
Cezary KucharskiDepartment of Chemical and Materials Engineering, Faculty of Engineering, University of Alberta, Edmonton, AB, Canada.
Remant Bahadur K CDepartment of Chemical and Materials Engineering, Faculty of Engineering, University of Alberta, Edmonton, AB, Canada.
Mohammad NasrullahDepartment of Chemical and Materials Engineering, Faculty of Engineering, University of Alberta, Edmonton, AB, Canada.ORCID 0000-0003-1346-355X
Xiaoyan JiangDepartment of Medical Genetics, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.
Hasan UludağDepartment of Chemical and Materials Engineering, Faculty of Engineering, University of Alberta, Edmonton, AB, Canada.ORCID 0000-0002-1118-4170
Joseph BrandweinDepartment of Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada.
University of Alberta · CAUniversity of British Columbia · CA

Funding

CIHR MOP 142202
6 · The paper itself

Abstract

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

Indexed as

B-LymphocytesCell Line, TumorDown-RegulationDrug CarriersFusion Proteins, bcr-ablGene SilencingHumansLinoleic AcidPolyethyleneiminePolymersPrecursor Cell Lymphoblastic Leukemia-LymphomaRNA, Double-StrandedRNA InterferenceRNA, Small InterferingSTAT5 Transcription FactorTumor Suppressor ProteinsDrug CarriersFusion Proteins, bcr-ablLinoleic AcidPolyethyleneiminePolymersRNA, Double-StrandedRNA, Small InterferingSTAT5A protein, humanSTAT5 Transcription FactorTumor Suppressor Proteins

Identifiers

PMID34157051
PMCPMC8219370
OpenAlexW3176924520

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.