A Triplex Ribozyme Expression System Based on a Single Hairpin Ribozyme

Aquino‐Jarquín, Guillermo; Benítez‐Hess, María Luisa; DiPaolo, Joseph A.; Álvarez-Salas, Luis Marat

doi:10.1089/oli.2008.0130

Cited by 5 publications

(1 citation statement)

References 24 publications

(20 reference statements)

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“…Ribozyme targeting HPV16 E6E7 transcripts (Rz170) suppressed cell growth and sensitized cervical cancer cells to chemotherapy and radiotherapy (120). To counteract size related problems due to cloning in plasmid vectors, the construct was modified to triplex ribozyme expression system that released processed ribozymes as a single transcript by a self-processing mechanism (121,122). However, these modifications did not increase ribozyme mediated inhibition more than 30% (122), and thus this approach required further improvement to make ribozymes a therapeutic moiety.…”

Section: Silencing Hpv Rna By Catalytic Oligonucleotidesmentioning

confidence: 99%

Therapeutic startegies for human papillomavirus infection and associated cancers

et al. 2018

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Human papillomavirus (HPV) infection is linked to development of cancer of cervix, vagina, vulva, penis, ano-genital and non-genital oro-pharyngeal sites. HPV being a sexually transmitted virus infects both genders equally but with higher chances of pathological outcome in women. In the absence of organized screening programs, women report HPV-infected lesions at relatively advanced stages where they are subjected to standard treatments that are not HPV-specific. HPV infection-driven lesions usually take 10-20 years for malignant progression and are preceded by well-characterized pre-cancer stages. Despite availability of window for pharmacological intervention, therapeutic that could eradicate HPV from infected lesions is currently lacking. A variety of experimental approaches have been made to address this lacuna and there has been significant progress in a number of lead molecules which are in different stages of clinical and pre-clinical development. Present review provides a brief overview of the magnitude of the problem and current status of research on promising lead molecules, formulations and therapeutic strategies that showed potential to translate to clinically-viable HPV therapeutics to counteract this reproductive health challenge.

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Section: Silencing Hpv Rna By Catalytic Oligonucleotidesmentioning

confidence: 99%

Therapeutic startegies for human papillomavirus infection and associated cancers

et al. 2018

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Design and Function of Triplex Hairpin Ribozymes

Aquino‐Jarquín

Rojas-Hernández

Álvarez-Salas

2010

Methods in Molecular Biology

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Triplex ribozymes allow for the individual activity of multiple trans-acting ribozymes producing higher target cleavage relative to tandem-expressed RZs. A triplex expression system based on a single hairpin ribozyme for the multiple expression (multiplex) vectors can be engineered to target RNAs with single or multiple antisense-accessible sites. System construction relies on triplex expression modules consisting of hairpin ribozyme cassettes flanked by ribozymes lacking catalytic domains. Multiplex vectors can be generated with single or multiple specificity by tandem cloning of triplex expression modules. Triplex ribozymes are initially tested in vitro using cis- and trans-cleavage assays against radioactive-labeled targets. In addition, triplex ribozymes are tested for cis and trans cleavage in vivo by transfection in cultured cells followed by ribonuclease protection assays (RPAs) and RT-PCR. The use of triplex configurations with multiplex ribozymes will provide the basis for the development of future RZ-based therapies and technologies.

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Inhibition of Human Papillomavirus Expression Using DNAzymes

Benítez‐Hess

Reyes-Gutiérrez

Álvarez-Salas

2011

Methods in Molecular Biology

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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.

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A Triplex Ribozyme Expression System Based on a Single Hairpin Ribozyme

Cited by 5 publications

References 24 publications

Therapeutic startegies for human papillomavirus infection and associated cancers

Therapeutic startegies for human papillomavirus infection and associated cancers

Design and Function of Triplex Hairpin Ribozymes

Inhibition of Human Papillomavirus Expression Using DNAzymes

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