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      Multifunctional RNA Nanoparticles

      rapid-communication

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          Abstract

          Our recent advancements in RNA nanotechnology introduced novel nanoscaffolds (nanorings); however, the potential of their use for biomedical applications was never fully revealed. As presented here, besides functionalization with multiple different short interfering RNAs for combinatorial RNA interference (e.g., against multiple HIV-1 genes), nanorings also allow simultaneous embedment of assorted RNA aptamers, fluorescent dyes, proteins, as well as recently developed RNA–DNA hybrids aimed to conditionally activate multiple split functionalities inside cells.

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          Automated 3D structure composition for large RNAs

          Mariusz Popenda, Marta Szachniuk, Maciej Antczak … (2012)
          Understanding the numerous functions that RNAs play in living cells depends critically on knowledge of their three-dimensional structure. Due to the difficulties in experimentally assessing structures of large RNAs, there is currently great demand for new high-resolution structure prediction methods. We present the novel method for the fully automated prediction of RNA 3D structures from a user-defined secondary structure. The concept is founded on the machine translation system. The translation engine operates on the RNA FRABASE database tailored to the dictionary relating the RNA secondary structure and tertiary structure elements. The translation algorithm is very fast. Initial 3D structure is composed in a range of seconds on a single processor. The method assures the prediction of large RNA 3D structures of high quality. Our approach needs neither structural templates nor RNA sequence alignment, required for comparative methods. This enables the building of unresolved yet native and artificial RNA structures. The method is implemented in a publicly available, user-friendly server RNAComposer. It works in an interactive mode and a batch mode. The batch mode is designed for large-scale modelling and accepts atomic distance restraints. Presently, the server is set to build RNA structures of up to 500 residues.
          Article 0 comments Cited 255 times – based on 0 reviews     Review now
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            Human Dicer preferentially cleaves dsRNAs at their termini without a requirement for ATP.

            Haidi Zhang, Fabrice Kolb, Vincent Brondani … (2002)
            Dicer is a multi-domain RNase III-related endonuclease responsible for processing double-stranded RNA (dsRNA) to small interfering RNAs (siRNAs) during a process of RNA interference (RNAi). It also catalyses excision of the regulatory microRNAs from their precursors. In this work, we describe the purification and properties of a recombinant human Dicer. The protein cleaves dsRNAs into approximately 22 nucleotide siRNAs. Accumulation of processing intermediates of discrete sizes, and experiments performed with substrates containing modified ends, indicate that Dicer preferentially cleaves dsRNAs at their termini. Binding of the enzyme to the substrate can be uncoupled from the cleavage step by omitting Mg(2+) or performing the reaction at 4 degrees C. Activity of the recombinant Dicer, and of the endogenous protein present in mammalian cell extracts, is stimulated by limited proteolysis, and the proteolysed enzyme becomes active at 4 degrees C. Cleavage of dsRNA by purifed Dicer and the endogenous enzyme is ATP independent. Additional experiments suggest that if ATP participates in the Dicer reaction in mammalian cells, it might be involved in product release needed for the multiple turnover of the enzyme.
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              Factors controlling nanoparticle pharmacokinetics: an integrated analysis and perspective.

              S M Moghimi, T Andresen, S Moein Moghimi (2012)
              Intravenously injected nanoparticulate drug carriers provide a wide range of unique opportunities for site-specific targeting of therapeutic agents to many areas within the vasculature and beyond. Pharmacokinetics and biodistribution of these carriers are controlled by a complex array of interrelated core and interfacial physicochemical and biological factors. Pertinent to realizing therapeutic goals, definitive maps that establish the interdependency of nanoparticle size, shape, and surface characteristics in relation to interfacial forces, biodistribution, controlled drug release, excretion, and adverse effects must be outlined. These concepts are critically evaluated and an integrated perspective is provided on the basis of the recent application of nanoscience approaches to nanocarrier design and engineering. The future of this exciting field is bright; some regulatory-approved products are already on the market and many are in late-phase clinical trials. With concomitant advances in extensive computational knowledge of the genomics and epigenomics of interindividual variations in drug responses, the boundaries toward development of personalized nanomedicines can be pushed further.
              Article 0 comments Cited 143 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): Nano Lett
                Journal ID (iso-abbrev): Nano Lett
                Journal ID (publisher-id): nl
                Journal ID (coden): nalefd
                Title: Nano Letters
                Publisher: American Chemical Society
                ISSN (Print): 1530-6984
                ISSN (Electronic): 1530-6992
                Publication date PMC-release: 30 September 2015
                Publication date (Electronic): 30 September 2014
                Publication date (Print): 08 October 2014
                Volume: 14
                Issue: 10
                Pages: 5662-5671
                Affiliations
                [† ]Basic Research Laboratory, Center for Cancer Research, National Cancer Institute , Frederick, Maryland 21702, United States
                [‡ ]Basic Science Program, Leidos Biomedical Research, Inc., NCI Center for Cancer Research, Frederick National Laboratory for Cancer Research , Frederick, Maryland 21702, United States
                [§ ]National Center for Macromolecular Imaging, Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine , Houston, Texas 77030, United States
                [∥ ]HIV Drug Resistance Program, National Cancer Institute , Frederick, Maryland 21702, United States
                [⊥ ]Food and Drug Administration, Center for Biologics Evaluation and Research, Office of Cellular, Tissue and Gene Therapies , Silver Spring, Maryland 20993, United States
                [# ]Department of Chemistry, Seattle Pacific University , Seattle, Washington 98119, United States
                [∇ ]Department of Chemistry and Biochemistry, Biomolecular Science and Engineering Program, University of California , Santa Barbara, California 93106-9510, United States
                Author notes
                [* ]Phone: 301-846-5536; fax: 301-846-5598; e-mail: shapirbr@ 123456mail.nih.gov .
                Article
                DOI: 10.1021/nl502385k
                PMC ID: 4189619
                PubMed ID: 25267559
                SO-VID: 51803d0e-2362-4041-b61b-42cf1b1946a6
                Copyright © Copyright © 2014 American Chemical Society
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                History
                Date received : 25 June 2014
                Date revision received : 27 August 2014
                Funding
                National Institutes of Health, United States
                Categories
                Subject: Letter
                Custom metadata
                document-id-old-9 nl502385k
                document-id-new-14 nl-2014-02385k
                ccc-price

                ScienceOpen disciplines: Nanotechnology
                Keywords: rna nanotechnology,rna nanoparticles,rna interference,aptamers,rna−dna hybrid reassociation
                Data availability:
                ScienceOpen disciplines: Nanotechnology
                Keywords: rna nanotechnology, rna nanoparticles, rna interference, aptamers, rna−dna hybrid reassociation

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