title: Inhibition of human papillomavirus expression using DNAzymes.
abstract: Deoxyribozymes (DXZs) are catalytic oligodeoxynucleotides capable of performing diverse functions including the specific cleavage of a target RNA. These molecules represent a new type of therapeutic oligonucleotides combining the efficiency of ribozymes and the intracellular endurance and simplicity of modified antisense oligonucleotides. Commonly used DXZs include the 8-17 and 10-23 motifs, which have been engineered to destroy disease-associated genes with remarkable efficiency. Targeting DXZs to disease-associated transcripts requires extensive biochemical testing to establish target RNA accessibility, catalytic efficiency, and nuclease sensibility. The usage of modified nucleotides to render nuclease-resistance DXZs must be counterweighted against deleterious consequences on catalytic activity. Further intracellular testing is required to establish the effect of microenvironmental conditions on DXZ activity and off-target issues. Application of modified DXZs to cervical cancer results in specific growth inhibition, cell death, and apoptosis. Thus, DXZs represent a highly effective antisense moiety with minimal secondary effects.
authors: Laboratorio de Terapia Génica, Departamento de Genética y Biología Molecular, CINVESTAV, Av. IPN 2508, México D.F., 07360, México. marial@cinvestav.mx
authors: María Luisa
authors: ML
authors: Benítez-Hess
authors: Pablo
authors: P
authors: Reyes-Gutiérrez
authors: Luis Marat
authors: LM
authors: Alvarez-Salas
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D020134:Catalytic Domain; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002855:Chromatography, Thin Layer; D021881:DNA, Catalytic / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D004277:DNA, Single-Stranded / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D052162:Human papillomavirus 16 / Q000187:drug effects* / Q000254:growth & development; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods*; D009838:Oligodeoxyribonucleotides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D016376:Oligonucleotides, Antisense / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D030361:Papillomavirus Infections / Q000150:complications / Q000188:drug therapy* / Q000821:virology; D012333:RNA, Messenger / Q000378:metabolism*; D012367:RNA, Viral / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000209:etiology / Q000821:virology; D014779:Virus Replication / Q000187:drug effects
chemical_list: D021881:DNA, Catalytic; D004277:DNA, Single-Stranded; D009838:Oligodeoxyribonucleotides; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D012367:RNA, Viral