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      Innovations in Oligonucleotide Drug Delivery

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          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          ABSTRACT:

          Oligonucleotides (ONs) are a new class of therapeutic compounds under investigation for the treatment of a variety of disease states, such as cancer and HIV, and for FDA approval of an anti-CMV retinitis antisense molecule (Vitravene™, Isis Pharmaceuticals). However, these molecules are limited not only by poor cellular uptake, but also by a general lack of understanding regarding the mechanism(s) of ON cellular uptake. As a result, various delivery vehicles have been developed that circumvent the proposed mechanism of uptake, endocytosis, while improving target specific delivery and/or drug stability. This review describes various traditional and novel delivery mechanisms that have been employed to improve ON cellular delivery, cost effectiveness, and therapeutic efficacy. © 2003 Wiley-Liss, Inc. and the American Pharmacists Association

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          An inverted hexagonal phase of cationic liposome-DNA complexes related to DNA release and delivery.

          J Rädler, I Koltover, Cyrus Safinya … (1998)
          A two-dimensional columnar phase in mixtures of DNA complexed with cationic liposomes has been found in the lipid composition regime known to be significantly more efficient at transfecting mammalian cells in culture compared to the lamellar (LalphaC) structure of cationic liposome-DNA complexes. The structure, derived from synchrotron x-ray diffraction, consists of DNA coated by cationic lipid monolayers and arranged on a two-dimensional hexagonal lattice (HIIC). Two membrane-altering pathways induce the LalphaC --> HIIC transition: one where the spontaneous curvature of the lipid monolayer is driven negative, and another where the membrane bending rigidity is lowered with a new class of helper-lipids. Optical microscopy revealed that the LalphaC complexes bind stably to anionic vesicles (models of cellular membranes), whereas the more transfectant HIIC complexes are unstable and rapidly fuse and release DNA upon adhering to anionic vesicles.
          Article 0 comments Cited 177 times – based on 0 reviews     Review now
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            Inhibition of Rous sarcoma virus replication and cell transformation by a specific oligodeoxynucleotide.

            H. Stephenson, P Zamecnik (1977)
            The tridecamer d(A-A-T-G-G-T-A-A-A-A-T-G-G), which is complementary to 13 nucleotides of the 3'- and 5'-reiterated terminal sequences of Rous sarcoma virus 35S RNA, was added to chick embryo fibroblast tissue cultures infected with Rous sarcoma virus. Inhibition of virus production resulted. The inference emerges that the tridecamer and its counterpart with blocked 3'- and 5'-hydroxyl termini enter the chick fibroblast cells, hybridize with the terminal reiterated sequences at the 3' and 5' ends of the 35S RNA, and interfere with one or more steps involved in viral production and cell transformation. Likely sites of action are (i) the circularization step of the proviral DNA intermediate, and (ii) the initiation of translation, the latter being described in the following communication [Stephenson, M. L. & Zamecnik, P. C. (1978) Proc. Natl. Acad. Sci. USA 75, 285--288].
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              Mechanism of oligonucleotide release from cationic liposomes.

              F Szoka, O Zelphati (1996)
              We propose a mechanism for oligonucleotide (ODN) release from cationic lipid complexes in cells that accounts for various observations on cationic lipid-nucleic acid-cell interactions. Fluorescent confocal microscopy of cells treated with rhodamine-labeled cationic liposome/ fluorescein-labeled ODN (F-ODN) complexes show the F-ODN separates from the lipid after internalization and enters the nucleus leaving the fluorescent lipid in cytoplasmic structures. ODN displacement from the complex was studied by fluorescent resonance energy transfer. Anionic liposome compositions (e.g., phosphatidylserine) that mimic the cytoplasmic facing monolayer of the cell membrane released ODN from the complex at about a 1:1 (-/+) charge ratio. Release was independent of ionic strength and pH. Physical separation of the F-ODN from monovalent and multivalent cationic lipids was confirmed by gel electrophoresis. Fluid but not solid phase anionic liposomes are required, whereas the physical state of the cationic lipids does not effect the release. Water soluble molecules with a high negative linear charge density, dextran sulfate, or heparin also release ODN. However, ATP, spermidine, spermine, tRNA, DNA, polyglutamic acid, polylysine, bovine serum albumin, or histone did not release ODN, even at 100-fold charge excess (-/+). Based upon these results, we propose that the complex, after internalization by endocytosis, induces flip-flop of anionic lipids from the cytoplasmic facing monolayer. Anionic lipids laterally diffuse into the complex and form a charged neutralized ion-pair with the cationic lipids. This leads to displacement of the ODN from the cationic lipid and its release into the cytoplasm.
              Article 0 comments Cited 81 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Melanie A. Lysik
                Journal
                Journal ID (nlm-ta): J Pharm Sci
                Journal ID (iso-abbrev): J Pharm Sci
                Title: Journal of Pharmaceutical Sciences
                Publisher: Elsevier
                ISSN (Print): 0022-3549
                ISSN (Electronic): 1520-6017
                Publication date PMC-release: 29 January 2016
                Publication date (Print): August 2003
                Publication date (Electronic): 29 January 2016
                Volume: 92
                Issue: 8
                Pages: 1559-1573
                Affiliations
                [1 ]Midwestern University, College of Pharmacy-Glendale, Department of Pharmaceutical Sciences, 19555 N 59 th Avenue, Glendale, Arizona 18308
                [2 ]Virginia Commonwealth University, Medical College of Virginia, School of Pharmacy, Department of Pharmaceutics, MCV Box 980533, Richmond, Virginia 23298
                Author notes
                [* ]Midwestern University, College of Pharmacy‐Glendale, Department of Pharmaceutical Sciences, 19555 N 59 th Avenue, Glendale, Arizona 18308. Telephone: 623‐572‐3578; Fax: 626‐572‐3550 mlysik@ 123456Arizona.midwester.edu
                Article
                Publisher ID: S0022-3549(16)31286-2
                DOI: 10.1002/jps.10399
                PMC ID: 7094321
                PubMed ID: 12884243
                SO-VID: 928787c6-ca9a-4738-b2ed-e409f8c9cf64
                Copyright © © 2003 Wiley-Liss, Inc.
                License:

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                Date received : 16 July 2002
                Date revision received : 17 October 2002
                Date accepted : 16 January 2003
                Categories
                Subject: Article

                ScienceOpen disciplines: Pharmacology & Pharmaceutical medicine
                Keywords: oligonucleotide,uptake,delivery,liposomes,carrier-mediated delivery,novel delivery methods
                Data availability:
                ScienceOpen disciplines: Pharmacology & Pharmaceutical medicine
                Keywords: oligonucleotide, uptake, delivery, liposomes, carrier-mediated delivery, novel delivery methods

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