Development of hammerhead ribozymes to modulate endogenous gene expression for functional studies

Fritz, Jason J.; Lewin, Alfred S.; Hauswirth, William W.; Agarwal, Anupam; Grant, Maria B.; Shaw, Lynn C.

doi:10.1016/s1046-2023(02)00233-5

Cited by 20 publications

(12 citation statements)

References 44 publications

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“…Potential cleavage sites were then evaluated for secondary folding structures around the G-U-C sequence using the theoretical lowest energy conformations calculated using the Mfold program (http://bioweb.pasteur.fr/seqanal/interfaces/mfold.html) (7). Only those sites for which the G-U-C sequence was in a single-stranded, nonbase-paired region were considered further.…”

Section: Methodsmentioning

confidence: 99%

Hammerhead Ribozyme-Mediated Knockdown of mRNA for Fibrotic Growth Factors: Transforming Growth Factor-Beta 1 and Connective Tissue Growth Factor

Robinson

Blalock

Yuan

et al. 2011

Methods in Molecular Biology

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Excessive scarring (fibrosis) is a major cause of pathologies in multiple tissues, including lung, liver, kidney, heart, cornea, and skin. The transforming growth factor- β (TGF- β) system has been shown to play a key role in regulating the formation of scar tissue throughout the body. Furthermore, connective tissue growth factor (CTGF) has been shown to mediate most of the fibrotic actions of TGF- β, including stimulation of synthesis of extracellular matrix and differentiation of fibroblasts into myofibroblasts. Currently, no approved drugs selectively and specifically regulate scar formation. Thus, there is a need for a drug that selectively targets the TGF- β cascade at the molecular level and has minimal off-target side effects. This chapter focuses on the design of hammerhead ribozymes, measurement of kinetic activity, and assessment of knockdown mRNAs of TGF- β and CTGF in cell cultures.

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Section: Methodsmentioning

confidence: 99%

Hammerhead Ribozyme-Mediated Knockdown of mRNA for Fibrotic Growth Factors: Transforming Growth Factor-Beta 1 and Connective Tissue Growth Factor

Robinson

Blalock

Yuan

et al. 2011

Methods in Molecular Biology

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“…When a sufficient number of homologous sequences are not available, this approach is not applicable. On the other hand, chemical probing approaches have been widely used to probe RNA secondary structures (Fritz et al, 2002;Gopinath, 2009;Tijerina et al, 2007). Among them, SHAPE chemistry ( Deigan et al, 2009;Weeks, 2010) has been shown to be a powerful approach for analyzing secondary structure at single nucleotide resolution for RNAs of any length (Merino et al, 2005;Wilkinson et al, 2006).…”

Section: Base Pairingmentioning

confidence: 99%

RNA Junction Motifs as Scaffolds for Construction of Multifunctional RNA Nanoparticles

Haque¹,

Guo²

2013

RNA Nanotechnology and Therapeutics

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“…By example, we will discuss here the different types of strategies as they might be applied to human retinal (or ocular) diseases, which is this labs venue of interest. The generic knockdown approach may also be used to suppress wild-type mRNA expression [137]. …”

Section: Strategies and Approaches For Ptgs Therapymentioning

confidence: 99%

Variables and Strategies in Development of Therapeutic Post-Transcriptional Gene Silencing Agents

Sullivan

Yau

Kolniak

et al. 2011

Journal of Ophthalmology

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Post-transcriptional gene silencing (PTGS) agents such as ribozymes, RNAi and antisense have substantial potential for gene therapy of human retinal degenerations. These technologies are used to knockdown a specific target RNA and its cognate protein. The disease target mRNA may be a mutant mRNA causing an autosomal dominant retinal degeneration or a normal mRNA that is overexpressed in certain diseases. All PTGS technologies depend upon the initial critical annealing event of the PTGS ligand to the target RNA. This event requires that the PTGS agent is in a conformational state able to support hybridization and that the target have a large and accessible single-stranded platform to allow rapid annealing, although such platforms are rare. We address the biocomplexity that currently limits PTGS therapeutic development with particular emphasis on biophysical variables that influence cellular performance. We address the different strategies that can be used for development of PTGS agents intended for therapeutic translation. These issues apply generally to the development of PTGS agents for retinal, ocular, or systemic diseases. This review should assist the interested reader to rapidly appreciate critical variables in PTGS development and facilitate initial design and testing of such agents against new targets of clinical interest.

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Development of hammerhead ribozymes to modulate endogenous gene expression for functional studies

Cited by 20 publications

References 44 publications

Hammerhead Ribozyme-Mediated Knockdown of mRNA for Fibrotic Growth Factors: Transforming Growth Factor-Beta 1 and Connective Tissue Growth Factor

Hammerhead Ribozyme-Mediated Knockdown of mRNA for Fibrotic Growth Factors: Transforming Growth Factor-Beta 1 and Connective Tissue Growth Factor

RNA Junction Motifs as Scaffolds for Construction of Multifunctional RNA Nanoparticles

Variables and Strategies in Development of Therapeutic Post-Transcriptional Gene Silencing Agents

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