Downregulation of TdT Expression through Splicing Modulation by Antisense Peptide Nucleic Acid (PNA)

2019 ◽  
Vol 20 (2) ◽  
pp. 168-178 ◽  
Author(s):  
Soheila Montazersaheb ◽  
Masoumeh Kazemi ◽  
Elahe Nabat ◽  
Peter E. Nielsen ◽  
Mohammad S. Hejazi
Keyword(s):  
Nucleic Acid ◽  
Cell Survival ◽  
Peptide Nucleic Acid ◽  
Lymphoblastic Leukemia ◽  
Pcr Analysis ◽  
Sequence Specificity ◽  
Apoptosis Induction ◽  
Base Mismatch ◽  
Splicing Patterns ◽  
Antisense Peptide

Background and Objective: Antisense oligonucleotides are able to modulate splicing patterns and offer therapeutic intervention for cancer and other diseases. Considering TdT potential as a target in cancer therapy, the present study aimed to investigate splicing alteration of TdT pre-mRNA in Molt-4 cells using peptide nucleic acid (PNA) octaarginine and cholic acid conjugates. Method: We examined 16 mer PNAs targeting 5' and 3' junctions of intron 7 and addressed their mRNA splicing modulation effects using RT-PCR analysis. We also tested corresponding 2-base mismatch PNAs to confirm the sequence specificity. In addition, protien level of TdT, apoptosis induction and cell viability rate were analysed. Results: PCR analysis showed that full match PNAs could modulate the splicing process, thereby producing a longer mRNA still including intron 7. PCR results also implied exon 7 skipping. In addition, reduced level of TdT protein in Molt-4 cells was observed. Downregulation of TdT level in PNA treated cells was accompanied by an increased rate of apoptosis and decreased the level of cell survival. Conclusion: PNA-mediated splicing modulation can specifically downregulate TdT expression. TdT dowregulation results in apoptosis induction and reduced cell survival in Molt-4 cells. These observations could draw more attentions to develop PNA based strategies for TdT suppression and consequent apoptosis induction in acute lymphoblastic leukemia.

scholarly journals Antimicrobial activity of antisense peptide–peptide nucleic acid conjugates against non-typeableHaemophilus influenzaein planktonic and biofilm forms

2016 ◽  
Vol 72 (1) ◽  
pp. 137-144 ◽  
Author(s):  
Taketo Otsuka ◽  
Aimee L. Brauer ◽  
Charmaine Kirkham ◽  
Erin K. Sully ◽  
Melinda M. Pettigrew ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Nucleic Acid ◽  
Peptide Nucleic Acid ◽  
Antisense Peptide

Approaches for Systemic Delivery of Dystrophin Antisense Peptide Nucleic Acid in the mdx Mouse Model

2020 ◽  
Author(s):  
Camilla Brolin ◽  
Ernest Wee Kiat Lim ◽  
Sylvestre Grizot ◽  
Caroline Holkmann Olsen ◽  
Niloofar Yavari ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Mouse Model ◽  
Peptide Nucleic Acid ◽  
Mdx Mouse ◽  
Systemic Delivery ◽  
Antisense Peptide

147: Intra Vesical Admininstration of Antisense Peptide Nucleic Acid Down Regulates Urothelial NGF Expression in Rat Model of Cystitis

2005 ◽  
Vol 173 (4S) ◽  
pp. 40-40
Author(s):  
Pradeep Tyagi ◽  
Michael B. Chancellor ◽  
Naoki Yoshimura ◽  
Leaf Huang
Keyword(s):  
Nucleic Acid ◽  
Rat Model ◽  
Peptide Nucleic Acid ◽  
Antisense Peptide

mazE Antitoxin of Toxin Antitoxin System and fbpA as Reliable Targets to Eradication of Neisseria meningitidis

2018 ◽  
Vol 24 (11) ◽  
pp. 1204-1210 ◽  
Author(s):  
Abbas Maleki ◽  
Sobhan Ghafourian ◽  
Iraj Pakzad ◽  
Behzad Badakhsh ◽  
Nourkhoda Sadeghifard
Keyword(s):  
Nucleic Acid ◽  
Neisseria Meningitidis ◽  
Peptide Nucleic Acid ◽  
Iron Uptake ◽  
Drug Target ◽  
Uptake System ◽  
Bacteriostatic Activity ◽  
In Vivo Analysis ◽  
Antisense Peptide

Background: Neisseria meningitidis is considered as a dangerous pathogen threatening human health. Nowadays, the new drug target is focused. Toxin antitoxin (TA) system is recently identified as an antimicrobial drug target. Also, in N. meningitidis, iron-uptake system could be an interesting target for drug discovery. Methods: In this study, fbpA and mazE genes were chosen as new antimicrobial targets and treated with antisense peptide nucleic acid (PNA). Firstly, they were evaluated by bioinformatics and then analyzed by experimental procedures. Secondly, the functionality was evaluated by stress conditions. Results: Our results interestingly demonstrated that when fbpA and mazE loci of N. meningitidis were targeted by antisense PNA, 8 µM concentration of fbpA-PNA as well as 30 µM concentration of mazE-PNA inhibited the growth of N. meningitides and were found to be bacteriostatic, whereas 10 μM concentration of fbpA-PNA showed bacteriocidal activity. Conclusion: Our findings demonstrated the bactriocidal activity of fbpA-PNA and bacteriostatic activity of mazEPNA. Therefore, mazE and fbpA genes should be potent antimicrobial targets but further analysis including in vivo analysis should be performed.

Structure−Activity Relationship Study on a Simple Cationic Peptide Motif for Cellular Delivery of Antisense Peptide Nucleic Acid

2005 ◽  
Vol 48 (21) ◽  
pp. 6741-6749 ◽  
Author(s):  
Klaus Albertshofer ◽  
Andrew M. Siwkowski ◽  
Edward V. Wancewicz ◽  
Christine C. Esau ◽  
Tanya Watanabe ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Peptide Nucleic Acid ◽  
Structure Activity Relationship ◽  
Activity Relationship ◽  
Peptide Motif ◽  
Cellular Delivery ◽  
Cationic Peptide ◽  
Structure Activity ◽  
Relationship Study ◽  
Antisense Peptide
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