A Suite of Therapeutically-Inspired Nucleic Acid Logic Systems for Conditional Generation of Single-Stranded and Double-Stranded Oligonucleotides
| Autor: | Mathias Viard, Nomongo Dorjsuren, Hadley Humbertson, Bruce A. Shapiro, Eckart Bindewald, Paul Zakrevsky |
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| Rok vydání: | 2018 |
| Předmět: |
General Chemical Engineering
Therapeutic treatment 02 engineering and technology Computational biology 010402 general chemistry 01 natural sciences Article lcsh:Chemistry chemistry.chemical_compound Gene expression conditional activation General Materials Science Oligonucleotide RNA RNA logic 021001 nanoscience & nanotechnology Non-coding RNA 0104 chemical sciences lcsh:QD1-999 chemistry nucleic acid therapeutic Nucleic acid functional RNA 0210 nano-technology Double stranded DNA |
| Zdroj: | Nanomaterials Volume 9 Issue 4 Nanomaterials, Vol 9, Iss 4, p 615 (2019) |
| ISSN: | 2079-4991 |
| Popis: | 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&prime modifications, while none contain any sequence restrictions on what can define the diagnostic trigger sequence or the functional oligonucleotide output. |
| Databáze: | OpenAIRE |
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