In vivo excision of a single targeted nucleotide from an mRNA by a <i>trans</i> excision-splicing ribozyme

Baum, Dana A.; Testa, Stephen M.

doi:10.1261/rna.2050505

Cited by 12 publications

(16 citation statements)

References 40 publications

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“…Expression of eukaryotic pathways in a prokaryote host would appear, at first hand, to be a redundant strategy because of incompatibilities in post-transcriptional mRNA processing. However, eukaryotic expression systems do exist [133], and modification of these or prokaryotic surrogates into 'superhosts' to bypass transcription, translation or biosynthetic barriers could become a reality in the future, for example, by the additional cloning of RNA processing enzymes [134]. Selection of an appropriate host is key to sustainable production on an industrial scale to sustain a future global supply.…”

Section: Molecular Genetic Approaches Towards Sustainable Supplymentioning

confidence: 99%

New Methods for Medicinal Chemistry - Universal Gene Cloning and Expression Systems for Production of Marine Bioactive Metabolites

Dunlap

Jaspars²,

Hranueli³

et al. 2006

CMC

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Natural products from symbiotic or commensal associations between marine invertebrate and microbial organisms show exceptional promise as pharmaceuticals in many therapeutic areas. An economic and sustainable global market supply due to difficulty of synthesis is cited as the main obstacle for exploitation of these otherwise exciting marine bioactive compounds. Different strategies have been evoked to overcome this impediment as long-term harvesting of wild stocks from the environment is considered unsound, and other modes of production based on biosynthesis, such as aquaculture, have not yet been proven as reliable. One option is to clone the genes encoding the biosynthetic expression of a lead metabolite into a surrogate host suitable for industrial-scale fermentation. To facilitate this goal we are developing a universal system to clone and express genes responsible for biosynthesis of natural products from both eukaryotic and prokaryotic partners of marine symbioses. The ability to harness the complete meta-transcriptome of entire biosynthetic pathways is particularly valuable where the biogenesis of a target natural product occurring within a complex symbiotic association is unclear.

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Section: Molecular Genetic Approaches Towards Sustainable Supplymentioning

confidence: 99%

New Methods for Medicinal Chemistry - Universal Gene Cloning and Expression Systems for Production of Marine Bioactive Metabolites

Dunlap

Jaspars²,

Hranueli³

et al. 2006

CMC

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show abstract

“…GI ribozymes engineered for trans-splicing reactions lack their 5'-exon or 3'-exon and contain designed P1 elements to bind given target RNAs. [8,15] Recently,M üller and co-workersd eveloped an improved system based on the Tetrahymena GI ribozyme,w hich achieved trans-excision splicing in E. coli cells. [9] It has been demonstrated that the ribozymes engineered for trans-splicing reactions target severalR NA sequences not only in Escherichiac oli cells [7,10,11] but also in mammalianc ells.…”

Section: Introductionmentioning

confidence: 99%

“…[8] Several trans-excision-splicing reactions have been reported to date. [8,15] Recently,M üller and co-workersd eveloped an improved system based on the Tetrahymena GI ribozyme,w hich achieved trans-excision splicing in E. coli cells. [16,17] These examples suggested that it might be possible to engineer self-splicinga nd related reactions of GI ribozymes to achieve complex editing of two or more RNA sequences in ac ooperative manner.…”

Section: Introductionmentioning

confidence: 99%

Heterodimerization of Group I Ribozymes Enabling Exon Recombination through Pairs of Cooperative trans‐Splicing Reactions

et al. 2017

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Group I (GI) self-splicing ribozymes are attractive tools for biotechnology and synthetic biology. Several trans-splicing and related reactions based on GI ribozymes have been developed for the purpose of recombining their target mRNA sequences. By combining trans-splicing systems with rational modular engineering of GI ribozymes it was possible to achieve more complex editing of target RNA sequences. In this study we have developed a cooperative trans-splicing system through rational modular engineering with use of dimeric GI ribozymes derived from the Tetrahymena group I intron ribozyme. The resulting pairs of ribozymes exhibited catalytic activity depending on their selective dimerization. Rational modular redesign as performed in this study would facilitate the development of sophisticated regulation of double or multiple trans-splicing reactions in a cooperative manner.

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“…Ribozymes have been engineered to repair RNA through removal or addition of small internal fragments as well as single nucleotides based on the group I intron ribozyme [224][225][226] or on the hairpin ribozyme [227]. These systems are true repair systems but until now have been applied only in vitro.…”

Section: Other Strategies Of Ribozyme-mediated Revision Of Rnamentioning

confidence: 99%

Drugs Made of RNA: Development and Application of Engineered RNAs for Gene Therapy

Drude¹,

Dombos²,

Vauléon

et al. 2007

MRMC

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During the past decade, RNA has become a focus of investigation into new therapeutic schemes: antisense RNA, interfering RNA and trans-cleaving ribozymes are used to silence undesired gene expression. As an additional option with its own therapeutic potential, ribozymes may be employed to specifically alter the sequence of RNA. Among these RNA based strategies the mode of action varies: while antisense and interfering RNAs are capable of making specific contacts to other RNA molecules with the result of employing the cellular machinery for degradation of the RNA target, trans-cleaving ribozymes fold into specific three-dimensional structures to form catalytic centres and to specifically cleave a chosen RNA target. Beyond this, trans-splicing ribozymes have been engineered to first cleave a RNA target followed by ligation of a new RNA fragment delivered with the ribozyme. The latter strategy potentially extends the application of ribozymes from inhibition of gene expression to RNA repair, i. e. correction of genetic disorders at the level of RNA, and has already shown promising results in cell culture experiments. On the other side, advances in RNA synthesis, ribozyme engineering, delivery methods and expression systems have greatly enhanced the prospects of ribozymes, antisense and interfering RNAs in gene therapy. This review provides an overview of existing strategies for potential RNA based gene therapy. It is focussed on the engineering of ribozymes and functional RNAs to be used as drugs and on the basic molecular principles of their action.

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In vivo excision of a single targeted nucleotide from an mRNA by a trans excision-splicing ribozyme

Cited by 12 publications

References 40 publications

New Methods for Medicinal Chemistry - Universal Gene Cloning and Expression Systems for Production of Marine Bioactive Metabolites

New Methods for Medicinal Chemistry - Universal Gene Cloning and Expression Systems for Production of Marine Bioactive Metabolites

Heterodimerization of Group I Ribozymes Enabling Exon Recombination through Pairs of Cooperative trans‐Splicing Reactions

Drugs Made of RNA: Development and Application of Engineered RNAs for Gene Therapy

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