title: Site-specific cleavage of mutant ABL mRNA by DNAzyme is facilitated by peptide nucleic acid binding to RNA substrate.
abstract: 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.
authors.affiliation: Department of Bioscience and Biotechnology, Konkuk University, Seoul, Republic of Korea.
authors.forename: Ji Eun
authors.initials: JE
authors.lastname: Kim
authors.forename: Soojin
authors.initials: S
authors.lastname: Yoon
authors.forename: Hyejung
authors.initials: H
authors.lastname: Mok
authors.forename: Woong
authors.initials: W
authors.lastname: Jung
authors.forename: Dong-Eun
authors.initials: DE
authors.lastname: Kim
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001483:Base Sequence; D001549:Benzamides; D045744:Cell Line, Tumor; D021881:DNA, Catalytic / Q000138:chemical synthesis / Q000235:genetics / Q000378:metabolism*; D016313:Genes, abl; D005818:Genetic Engineering; D006801:Humans; D000068877:Imatinib Mesylate; D051379:Mice; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D016376:Oligonucleotides, Antisense / Q000235:genetics; D020135:Peptide Nucleic Acids / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010879:Piperazines / Q000494:pharmacology; D020641:Polymorphism, Single Nucleotide; D011743:Pyrimidines / Q000494:pharmacology; D059367:RNA Cleavage / Q000187:drug effects; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D013379:Substrate Specificity; D014162:Transfection
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D021881:DNA, Catalytic; D016376:Oligonucleotides, Antisense; D020135:Peptide Nucleic Acids; D010879:Piperazines; D011743:Pyrimidines; D012333:RNA, Messenger; D000068877:Imatinib Mesylate