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Site‐specific cleavage of mutant ABL mRNA by DNAzyme is facilitated by peptide nucleic acid binding to RNA substrate
Author(s) -
Kim Ji Eun,
Yoon Soojin,
Mok Hyejung,
Jung Woong,
Kim Dong-Eun
Publication year - 2012
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2012.09.013
Subject(s) - deoxyribozyme , oligonucleotide , rna , nucleic acid , chemistry , microbiology and biotechnology , peptide nucleic acid , locked nucleic acid , mutant , dna , biochemistry , biology , gene
RNA‐cleaving DNAzymes were constructed to target the point mutation in the BCR–ABL transcript that causes imatinib resistance in leukemic cells. We examined the effect of 12mer peptide nucleic acids (PNAs) as facilitator oligonucleotides that bind to RNA substrate at the termini of the DNAzyme to improve DNAzyme‐mediated cleavage of full‐length RNA. When imatinib‐resistant cells were transfected with the facilitator PNA and DNAzyme, DNAzyme activity was enhanced and the cells were sensitized to imatinib treatment. Thus, facilitator PNA may be used to enhance activity of antisense oligonucleotide targeting the full‐length transcript.