| Effective delivery of antisense peptide nucleic acid oligomers into cells by anthrax protective antigen. | |
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MedLine Citation:
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PMID: 18774771 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Peptide nucleic acid (PNA) is highly stable and binds to complementary RNA and DNA with high affinity, but it resists cellular uptake, thereby limiting its bioavailability. We investigated whether protectiveantigen (PA, a non-toxic component of anthrax toxin) could transport antisense PNA oligomers into reporter cells that contain luciferase transgenes with mutant beta-globin IVS2 intronic inserts, which permit aberrant pre-mRNA splicing and impair luciferase expression. PNA oligomers antisense to mutant splice sites in these IVS2 inserts induced luciferase expression when effectively delivered into the cells. PNA 18-mers with C-terminal poly-lysine tails [PNA(Lys)(8)] demonstrated modest sequence-specific antisense activity by themselves at micromolar concentrations in luc-IVS2 reporter cell cultures. However, this activity was greatly amplified by PA. Antisense PNA(Lys)(8) with but not without PA also corrected the IVS2-654 beta-globin splice defect in cultured erythroid precursor cells from a patient with beta-thalassemia [genotype, IVS2-654(beta(0)/beta(E))], providing further evidence that anthrax PA can effectively transport antisense PNA oligomers into cells. |
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Authors:
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Daniel G Wright; Ying Zhang; John R Murphy |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2008-09-05 |
Journal Detail:
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Title: Biochemical and biophysical research communications Volume: 376 ISSN: 1090-2104 ISO Abbreviation: Biochem. Biophys. Res. Commun. Publication Date: 2008 Nov |
Date Detail:
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Created Date: 2008-10-16 Completed Date: 2008-10-30 Revised Date: 2010-09-21 |
Medline Journal Info:
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Nlm Unique ID: 0372516 Medline TA: Biochem Biophys Res Commun Country: United States |
Other Details:
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Languages: eng Pagination: 200-5 Citation Subset: IM |
Affiliation:
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Molecular Medicine Section, Department of Medicine, Boston University School of Medicine, Boston, MA, USA. dw341u@nih.gov |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Antigens, Bacterial
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metabolism* Bacterial Toxins / metabolism* Biological Transport Globins / genetics Humans Introns Luciferases / genetics Oligodeoxyribonucleotides, Antisense / genetics, metabolism* Peptide Nucleic Acids / genetics, metabolism* RNA Splice Sites RNA Splicing Transfection / methods* beta-Thalassemia / genetics |
| Grant Support | |
ID/Acronym/Agency:
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R21 CA112228-02/CA/NCI NIH HHS; R21CA11228/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antigens, Bacterial; 0/Bacterial Toxins; 0/Oligodeoxyribonucleotides, Antisense; 0/Peptide Nucleic Acids; 0/RNA Splice Sites; 0/anthrax toxin; 9004-22-2/Globins; EC 1.13.12.-/Luciferases |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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