Design, synthesis and DNA/RNA binding studies of nucleic acids comprising stereoregular and acyclic polycarbamate backbone: polycarbamate nucleic acids (PCNA)

Vangala, Madhuri; Kumar, Vaijayanti A.

doi:10.1039/c003405n

Cited by 18 publications

(9 citation statements)

References 36 publications

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“…2′-fluorine, 2′-O-methyl or 2′-amine) 108 . Other attempts include Peptide Nucleic Acids, Locked Nucleic Acids and their respective derivatives PolyCarbamate Nucleic Acids 109 or Locked Nucleic Acids with a bridge at different positions (2′-4′, 1′-3′) 110 . The 3′-end capping also improved the base pairing selectivity in duplex formation 111 .…”

Section: Challenges and Perspectivesmentioning

confidence: 99%

The emerging field of RNA nanotechnology

2010

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RNA can be designed and manipulated just like DNA while having different rules for base-pairing and displaying functions similar to proteins. The large variety of loops and motifs in RNA allow them to fold into numerous complicated structures. This diversity provides a platform for identifying viable building blocks for particle assemblies, substrate binding and manufacture engineering. RNA thermal stability allows production of multivalent nanostructures with defined stoichiometry. Here we review the unique qualities of RNA nanotechnology and their distinct properties inside the body. We describe techniques for constructing RNA nanoparticles from different building blocks and their applications in nanomedicine. Finally, we discuss challenges in predicting and synthesizing RNA and offer some perspectives on the yield and cost of RNA production.

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Section: Challenges and Perspectivesmentioning

confidence: 99%

The emerging field of RNA nanotechnology

2010

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“…5-BrU and 5-IU)[78], modifications of the phosphate linkage (e.g. phosphothioate and boranophosphate)[79], alteration of the ribose 2′ hydroxyl group (e.g., 2′-F, 2′-OMe, or 2′-NH 2 ) [53,80–82], synthesis of peptide nucleic acids (PNAs) [83], polycarbamate nucleic acids (PCNAs) [84], locked nucleic acids (LNAs) and their respective derivatives with a bridge at different positions (2′–4′, 1′–3′) [85], and capping of the 3′-end [86]. For therapeutic purpose, these modifications have also been applied to siRNAs.…”

Section: Overcome the First Barricade: Chemical Instability Of Rnasmentioning

confidence: 99%

Stable RNA nanoparticles as potential new generation drugs for cancer therapy

Shu

Sharma

et al. 2014

Advanced Drug Delivery Reviews

212

180

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Human genome sequencing revealed that only ~1.5% of the DNA sequence coded for proteins. More and more evidence has uncovered that a substantial part of the 98.5% so-called “junk” DNAs actually code for noncoding RNAs. Two milestones, chemical drugs and protein drugs, have already appeared in the history of drug development, and it is expected that the third milestone in drug development will be RNA drugs or drugs that target RNA. This review focuses on the development of RNA therapeutics for potential cancer treatment by applying RNA nanotechnology. A therapeutic RNA nanoparticle is unique in that its scaffold, ligand, and therapeutic component can all be composed of RNA. The special physicochemical properties lend to the delivery of siRNA, miRNA, ribozymes, or riboswitches; imaging using fluogenenic RNA; and targeting using RNA aptamers. With recent advances in solving the chemical, enzymatic, and thermodynamic stability issues, RNA nanoparticles have been found to be advantageous for in vivo applications due to their uniform nano-scale size, precise stoichiometry, polyvalent nature, low immunogenicity, low toxicity, and target specificity. In vivo animal studies have revealed that RNA nanoparticles can specifically target tumors with favorable pharmacokinetic and pharmacodynamic parameters without unwanted accumulation in normal organs. This review summarizes the key studies that have led to the detailed understanding of RNA nanoparticle formation as well as chemical and thermodynamic stability issue. The methods for RNA nanoparticle construction, and the current challenges in the clinical application of RNA nanotechnology, such as endosome trapping and production costs, are also discussed.

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“…The stability of RNA has long been an obstacle to its application as a construction material. Over the last few years, rapid progress has been made in improving the stability of RNA, which include chemical modifications of the bases (e.g., 5-Br-Ura and 5-I-Ura); modifications of the phosphate linkage (e.g., phosphothioate, boranophosphate); alteration of the 2¢ carbon (e.g., 2¢-F, 2¢-OMe or 2¢-NH 2 ) (Watts et al, 2008;Singh et al, 2010); synthesis of peptide nucleic acids, locked nucleic acids, and their respective derivatives; polycarbamate nucleic acids (Madhuri and Kumar, 2010) or locked nucleic acids with a bridge at different positions (2¢-4¢, 1¢-3¢) (Mathe and Perigaud, 2008); and capping of the 3¢-end (Patra and Richert, 2009). All these methods are very efficient in increasing RNase resistance in vitro and in vivo.…”

Section: Chemical Instabilitymentioning

confidence: 99%

Uniqueness, Advantages, Challenges, Solutions, and Perspectives in Therapeutics Applying RNA Nanotechnology

Guo

Haque

Hallahan

et al. 2012

Nucleic Acid Therapeutics

110

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The field of RNA nanotechnology is rapidly emerging. RNA can be manipulated with the simplicity characteristic of DNA to produce nanoparticles with a diversity of quaternary structures by self-assembly. Additionally RNA is tremendously versatile in its function and some RNA molecules display catalytic activities much like proteins. Thus, RNA has the advantage of both worlds. However, the instability of RNA has made many scientists flinch away from RNA nanotechnology. Other concerns that have deterred the progress of RNA therapeutics include the induction of interferons, stimulation of cytokines, and activation of other immune systems, as well as short pharmacokinetic profiles in vivo. This review will provide some solutions and perspectives on the chemical and thermodynamic stability, in vivo half-life and biodistribution, yield and production cost, in vivo toxicity and side effect, specific delivery and targeting, as well as endosomal trapping and escape.

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Design, synthesis and DNA/RNA binding studies of nucleic acids comprising stereoregular and acyclic polycarbamate backbone: polycarbamate nucleic acids (PCNA)

Abstract: The designed, chiral, acyclic polycarbamate nucleic acids (PCNA) exhibited sequence and orientation specific binding to nucleic acids. Complexes of PCNA with DNA were as stable as PNA:DNA complexes and those with RNA were as stable as natural DNA:RNA complexes.

Cited by 18 publications

References 36 publications

The emerging field of RNA nanotechnology

The emerging field of RNA nanotechnology

Stable RNA nanoparticles as potential new generation drugs for cancer therapy

Uniqueness, Advantages, Challenges, Solutions, and Perspectives in Therapeutics Applying RNA Nanotechnology

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