Document Detail

Effective delivery of antisense peptide nucleic acid oligomers into cells by anthrax protective antigen.
MedLine Citation:
PMID:  18774771     Owner:  NLM     Status:  MEDLINE    
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.
Daniel G Wright; Ying Zhang; John R Murphy
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2008-09-05
Journal Detail:
Title:  Biochemical and biophysical research communications     Volume:  376     ISSN:  1090-2104     ISO Abbreviation:  Biochem. Biophys. Res. Commun.     Publication Date:  2008 Nov 
Date Detail:
Created Date:  2008-10-16     Completed Date:  2008-10-30     Revised Date:  2013-06-05    
Medline Journal Info:
Nlm Unique ID:  0372516     Medline TA:  Biochem Biophys Res Commun     Country:  United States    
Other Details:
Languages:  eng     Pagination:  200-5     Citation Subset:  IM    
Molecular Medicine Section, Department of Medicine, Boston University School of Medicine, Boston, MA, USA.
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MeSH Terms
Antigens, Bacterial / metabolism*
Bacterial Toxins / metabolism*
Biological Transport
Globins / genetics
Luciferases / genetics
Oligodeoxyribonucleotides, Antisense / genetics,  metabolism*
Peptide Nucleic Acids / genetics,  metabolism*
RNA Splice Sites
RNA Splicing
Transfection / methods*
beta-Thalassemia / genetics
Grant Support
R21 CA112228-02/CA/NCI NIH HHS; R21CA11228/CA/NCI NIH HHS
Reg. No./Substance:
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

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