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• W2922433778 endingPage "994" @default.
• W2922433778 startingPage "983" @default.
• W2922433778 abstract "There are now several examples of nucleic-acid-displaying nanomaterials that have shown enhanced stability and improved cellular internalization of therapeutic DNA and RNA sequences. Nucleic-acid-displaying nanomaterials prolong the stability of nucleic acids in biological conditions while avoiding the need for external cationic transfection agents. They are made from biodegradable materials suitable for gene knockdown studies. The chemistry of a nucleic-acid-displaying scaffold can be built from a variety of sources – from amphiphilic block copolymers to surfactants – materials with easy-to-scale synthetic routes applicable to in vivo scale studies. There are now nucleic-acid-displaying nanomaterials that can be used for the codelivery of small-molecule drugs, enabling simultaneous delivery of charged oligonucleotides with hydrophobic drugs in a single formulation. Nanoscale structures of therapeutic nucleic acids have shown enormous potential to help clinicians realize the promise of personaliz ed medicine using gene-specific treatments. With the advent of better sequencing through bioinformatic approaches and advancements in nucleic acid stabilization chemistries, the field of synthetic nucleic acid nanomaterials has advanced tremendously. This review focuses on an emerging strategy geared at gene silencing without the use of traditional polycation-based transfection agents and discusses how such nanostructures are being chemically tailored to navigate biological systems to improve their circulation time and biodistribution. We also address important challenges moving forward, including quantification of delivery and the multiplexing of sequences for regulating gene networks – a goal well suited for this unique class of materials. Nanoscale structures of therapeutic nucleic acids have shown enormous potential to help clinicians realize the promise of personaliz ed medicine using gene-specific treatments. With the advent of better sequencing through bioinformatic approaches and advancements in nucleic acid stabilization chemistries, the field of synthetic nucleic acid nanomaterials has advanced tremendously. This review focuses on an emerging strategy geared at gene silencing without the use of traditional polycation-based transfection agents and discusses how such nanostructures are being chemically tailored to navigate biological systems to improve their circulation time and biodistribution. We also address important challenges moving forward, including quantification of delivery and the multiplexing of sequences for regulating gene networks – a goal well suited for this unique class of materials. family of RNA-binding proteins involved in gene silencing pathways. Responsible for the sequence-specific cleavage of mRNA when bound to short single stranded RNA such as siRNA. molecules composed of both hydrophobic and hydrophilic chemistries. short DNA sequences that initiate gene silencing through hybridization with mRNA. The formation of a DNA–mRNA duplex initiates RNaseH-mediated degradation that prevents protein translation. concentration of surfactant molecules at which micelles will form rather than remain separate in solution. DNA molecules that catalyze reactions in the presence of metal ions derived from in vitro selections. For example, DNAzymes can be evolved to target and cleave RNA molecules resulting in highly specific mRNA cleavage activity. duration of time that a molecule is stable before 50% of it degrades. In this context, most ONs have a short half-life (a few minutes) in cells in their native form without further chemical modification due to enzymatic degradation pathways. combining multiple molecules onto a single platform. In the context of gene regulation, it is common to use pools or cocktails of siRNA sequences against a single mRNA target to increase the likelihood of gene silencing. It can also refer to the use of multiple different siRNA sequences against different mRNA targets. nanoscale nucleic acid structures that (i) present dense displays of nucleic acid ligands, and (ii) degrade into structures which enhance nucleic acid stability and/or endosomal escape capacity. nucleic acid–surfactant conjugates crosslinked into micelle-like structures. Can be used for the delivery of TNAs and/or hydrophobic small molecules. use of polymers to shield the exposure of oligonucleotides on nanoscale polymeric structures for improved stability and biodistribution properties. commonly used cationic polymer for transfection of oligonucleotides into cells. Can display varying levels of primary, secondary, and tertiary amines, useful for electrostatically associating with the negatively charged phosphate backbone of RNA and DNA. RNA molecules that can accelerate a chemical or biochemical reaction, often in the presence of metal cations. a multi-ribonucleoprotein complex which incorporates mRNA and short single stranded RNA such as siRNA and miRNA for gene silencing. cellular mechanism in which dsRNA molecules are processed into shorter RNA fragments that can lower gene expression. spherically displayed nucleic acids densely functionalized on the surface of a nanoscale particle or colloid. chemical reagents that enable nucleic acids to undergo cellular uptake, either through shielding their negative charge, decreasing their polarity, or engaging in active receptor-mediated uptake." @default.
• W2922433778 created "2019-03-22" @default.
• W2922433778 creator A5030064573 @default.
• W2922433778 creator A5085760661 @default.
• W2922433778 creator A5086467511 @default.
• W2922433778 date "2019-09-01" @default.
• W2922433778 modified "2023-10-18" @default.
• W2922433778 title "Towards Self-Transfecting Nucleic Acid Nanostructures for Gene Regulation" @default.
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• W2922433778 doi "https://doi.org/10.1016/j.tibtech.2019.01.008" @default.
• W2922433778 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30879697" @default.
• W2922433778 hasPublicationYear "2019" @default.

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