RNA Toehold Interactions Initiate Conditional Gene Silencing

Zakrevsky, Paul; Bindewald, Eckart; Shapiro, Bruce A.

doi:10.1515/rnan-2016-0002

Cited by 2 publications

(1 citation statement)

References 11 publications

(11 reference statements)

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“…Here, we present the design of several new systems for the conditional release of single-stranded (ss) and double-stranded (ds) nucleic acid constructs that are specifically tailored to meet these criteria of ideal characteristics, which many existing systems fail to adequately satisfy. These designs are influenced by several existing nucleic acid technologies such as cognate RNA/DNA hybrids, molecular beacons, and trigger-responsive multi-stranded switch constructs [21,31,32,33,34], with the aim to take the most favorable characteristics from existing systems and create derivative systems with improved features [35]. Within each construct, the diagnostic region is structurally separated from the oligonucleotide payload, resulting in systems where input and output sequences are completely decoupled and impart no sequence constraints on one another.…”

Section: Introductionmentioning

confidence: 99%

A Suite of Therapeutically-Inspired Nucleic Acid Logic Systems for Conditional Generation of Single-Stranded and Double-Stranded Oligonucleotides

et al. 2019

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Several varieties of small nucleic acid constructs are able to modulate gene expression via one of a number of different pathways and mechanisms. These constructs can be synthesized, assembled and delivered to cells where they are able to impart regulatory functions, presenting a potential avenue for the development of nucleic acid-based therapeutics. However, distinguishing aberrant cells in need of therapeutic treatment and limiting the activity of deliverable nucleic acid constructs to these specific cells remains a challenge. Here, we designed and characterized a collection of nucleic acids systems able to generate and/or release sequence-specific oligonucleotide constructs in a conditional manner based on the presence or absence of specific RNA trigger molecules. The conditional function of these systems utilizes the implementation of AND and NOT Boolean logic elements, which could ultimately be used to restrict the release of functionally relevant nucleic acid constructs to specific cellular environments defined by the high or low expression of particular RNA biomarkers. Each system is generalizable and designed with future therapeutic development in mind. Every construct assembles through nuclease-resistant RNA/DNA hybrid duplex formation, removing the need for additional 2′-modifications, while none contain any sequence restrictions on what can define the diagnostic trigger sequence or the functional oligonucleotide output.

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Section: Introductionmentioning

confidence: 99%

A Suite of Therapeutically-Inspired Nucleic Acid Logic Systems for Conditional Generation of Single-Stranded and Double-Stranded Oligonucleotides

et al. 2019

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Preparation of a Conditional RNA Switch

et al. 2017

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RNA has gained great interest for use in biomedical and therapeutic applications. This is due in part to RNA's ability to perform multiple functions, including the regulation of endogenously expressed genes. However, the ability of RNA based drugs to distinguish target diseased cells from healthy tissue remains challenging. Here we present methods for the production of a recently developed conditional RNA switch that releases a Dicer substrate RNA in response to interaction with a specific RNA biomarker.

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RNA Toehold Interactions Initiate Conditional Gene Silencing

Cited by 2 publications

References 11 publications

A Suite of Therapeutically-Inspired Nucleic Acid Logic Systems for Conditional Generation of Single-Stranded and Double-Stranded Oligonucleotides

A Suite of Therapeutically-Inspired Nucleic Acid Logic Systems for Conditional Generation of Single-Stranded and Double-Stranded Oligonucleotides

Preparation of a Conditional RNA Switch

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