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Exploring a peptide nucleic acid-based antisense approach for CD5 targeting in chronic lymphocytic leukemia
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Exploring a peptide nucleic acid-based antisense approach for CD5 targeting in chronic lymphocytic leukemia
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Journal Article
Exploring a peptide nucleic acid-based antisense approach for CD5 targeting in chronic lymphocytic leukemia
2022
Overview
We herein report an innovative antisense approach based on Peptide Nucleic Acids (PNAs) to down-modulate CD5 expression levels in chronic lymphocytic leukemia (CLL). Using bioinformatics tools, we selected a 12-mer tract of the CD5 mRNA as the molecular target and synthesized the complementary and control PNA strands bearing a serine phosphate dipeptide tail to enhance their water solubility and bioavailability. The specific recognition of the 12-mer DNA strand, corresponding to the target mRNA sequence by the complementary PNA strand, was confirmed by non-denaturing polyacrylamide gel electrophoresis, thermal difference spectroscopy, circular dichroism (CD), and CD melting studies. Cytofluorimetric assays and real-time PCR analysis demonstrated the downregulation of CD5 expression due to incubation with the anti-CD5 PNA at RNA and protein levels in Jurkat cell line and peripheral blood mononuclear cells from B-CLL patients. Interestingly, we also observed that transfection with the anti-CD5 PNA increases apoptotic response induced by fludarabine in B-CLL cells. The herein reported results suggest that PNAs could represent a potential candidate for the development of antisense therapeutic agents in CLL.
Publisher
Public Library of Science,Public Library of Science (PLoS)
Subject
/ B cells
/ Chronic lymphocytic leukemia
/ DNA
/ Humans
/ Leukemia
/ Leukemia, Lymphocytic, Chronic, B-Cell - drug therapy
/ Leukemia, Lymphocytic, Chronic, B-Cell - genetics
/ Medicine
/ Medicine and Health Sciences
/ mRNA
/ Oligonucleotides, Antisense - genetics
/ Oligonucleotides, Antisense - pharmacology
/ Peptide Nucleic Acids - chemistry
/ Peptides
/ Peripheral blood mononuclear cells
/ Pharmacy
