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  1. Article ; Online: Advances in Antisense Oligonucleotide Development for Target Identification, Validation, and as Novel Therapeutics

    Moizza Mansoor / Alirio J. Melendez

    Gene Regulation and Systems Biology, Vol 2, Pp 275-

    2008  Volume 295

    Abstract: Antisense oligonucleotides (As-ODNs) are single stranded, synthetically prepared strands of deoxynucleotide sequences, usually 18–21 nucleotides in length, complementary to the mRNA sequence of the target gene. As-ODNs are able to selectively bind ... ...

    Abstract Antisense oligonucleotides (As-ODNs) are single stranded, synthetically prepared strands of deoxynucleotide sequences, usually 18–21 nucleotides in length, complementary to the mRNA sequence of the target gene. As-ODNs are able to selectively bind cognate mRNA sequences by sequence-specific hybridization. This results in cleavage or disablement of the mRNA and, thus, inhibits the expression of the target gene. The specificity of the As approach is based on the probability that, in the human genome, any sequence longer than a minimal number of nucleotides (nt), 13 for RNA and 17 for DNA, normally occurs only once. The potential applications of As-ODNs are numerous because mRNA is ubiquitous and is more accessible to manipulation than DNA. With the publication of the human genome sequence, it has become theoretically possible to inhibit mRNA of almost any gene by As-ODNs, in order to get a better understanding of gene function, investigate its role in disease pathology and to study novel therapeutic targets for the diseases caused by dysregulated gene expression. The conceptual simplicity, the availability of gene sequence information from the human genome, the inexpensive availability of synthetic oligonucleotides and the possibility of rational drug design makes As-ODNs powerful tools for target identification, validation and therapeutic intervention. In this review we discuss the latest developments in antisense oligonucleotide design, delivery, pharmacokinetics and potential side effects, as well as its uses in target identification and validation, and finally focus on the current developments of antisense oligonucleotides in therapeutic intervention in various diseases.
    Keywords Antisense ; oligonuclotides ; gene silencing ; gene therapy ; Biology (General) ; QH301-705.5 ; Science ; Q ; DOAJ:Biology ; DOAJ:Biology and Life Sciences
    Subject code 610
    Language English
    Publishing date 2008-01-01T00:00:00Z
    Publisher Libertas Academica
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Advances in antisense oligonucleotide development for target identification, validation, and as novel therapeutics.

    Mansoor, Moizza / Melendez, Alirio J

    Gene regulation and systems biology

    2008  Volume 2, Page(s) 275–295

    Abstract: Antisense oligonucleotides (As-ODNs) are single stranded, synthetically prepared strands of deoxynucleotide sequences, usually 18-21 nucleotides in length, complementary to the mRNA sequence of the target gene. As-ODNs are able to selectively bind ... ...

    Abstract Antisense oligonucleotides (As-ODNs) are single stranded, synthetically prepared strands of deoxynucleotide sequences, usually 18-21 nucleotides in length, complementary to the mRNA sequence of the target gene. As-ODNs are able to selectively bind cognate mRNA sequences by sequence-specific hybridization. This results in cleavage or disablement of the mRNA and, thus, inhibits the expression of the target gene. The specificity of the As approach is based on the probability that, in the human genome, any sequence longer than a minimal number of nucleotides (nt), 13 for RNA and 17 for DNA, normally occurs only once. The potential applications of As-ODNs are numerous because mRNA is ubiquitous and is more accessible to manipulation than DNA. With the publication of the human genome sequence, it has become theoretically possible to inhibit mRNA of almost any gene by As-ODNs, in order to get a better understanding of gene function, investigate its role in disease pathology and to study novel therapeutic targets for the diseases caused by dysregulated gene expression. The conceptual simplicity, the availability of gene sequence information from the human genome, the inexpensive availability of synthetic oligonucleotides and the possibility of rational drug design makes As-ODNs powerful tools for target identification, validation and therapeutic intervention. In this review we discuss the latest developments in antisense oligonucleotide design, delivery, pharmacokinetics and potential side effects, as well as its uses in target identification and validation, and finally focus on the current developments of antisense oligonucleotides in therapeutic intervention in various diseases.
    Language English
    Publishing date 2008-09-22
    Publishing country United States
    Document type Journal Article
    ISSN 1177-6250
    ISSN (online) 1177-6250
    DOI 10.4137/grsb.s418
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Recent trials for FTY720 (fingolimod): a new generation of immunomodulators structurally similar to sphingosine.

    Mansoor, Moizza / Melendez, Alirio J

    Reviews on recent clinical trials

    2008  Volume 3, Issue 1, Page(s) 62–69

    Abstract: Most of the conventional immunosuppressive drugs act by inhibiting the activation of enzymes, production of cytokines or proliferation of immune cells. Recently much attention is given to a new class of inhibitors that act by counteracting the functions ... ...

    Abstract Most of the conventional immunosuppressive drugs act by inhibiting the activation of enzymes, production of cytokines or proliferation of immune cells. Recently much attention is given to a new class of inhibitors that act by counteracting the functions of the lysophospholid sphingosine-1-phosphate (S1P). S1P is emerging as a potent stimulator of several immune cells and is critical for lymphocyte migration. The sphingosine analogue, FTY720 (fingolimod), a high affinity agonist of sphingosine-1-phosphate type-1 receptor (S1P-1), acts primarily by sequestering lymphocytes within peripheral lymphoid organs rendering them incapable of migrating to the sites of inflammation. Phase I, II and III, clinical trials comparing the efficacy of FTY720 containing regimens to conventional immunosuppressive regimens in de novo renal transplant patients, have been conducted. Moreover, clinical trials are also on-going in patients with relapsing-remitting multiple sclerosis showing obvious benefit for patients receiving FTY720. In this review, we focus on the transition of this novel compound from bench to clinical trials, and discuss the clinical potential of this drug in autoimmune diseases and in transplantation immunology.
    MeSH term(s) Animals ; Clinical Trials as Topic ; Disease Models, Animal ; Fingolimod Hydrochloride ; Humans ; Immune System Diseases/drug therapy ; Immunosuppressive Agents/chemistry ; Immunosuppressive Agents/pharmacology ; Immunosuppressive Agents/therapeutic use ; Propylene Glycols/chemistry ; Propylene Glycols/pharmacology ; Propylene Glycols/therapeutic use ; Sphingosine/analogs & derivatives ; Sphingosine/chemistry ; Sphingosine/pharmacology ; Sphingosine/therapeutic use
    Chemical Substances Immunosuppressive Agents ; Propylene Glycols ; Fingolimod Hydrochloride (G926EC510T) ; Sphingosine (NGZ37HRE42)
    Language English
    Publishing date 2008-05-13
    Publishing country United Arab Emirates
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2251879-4
    ISSN 1876-1038 ; 1574-8871
    ISSN (online) 1876-1038
    ISSN 1574-8871
    DOI 10.2174/157488708783330486
    Database MEDical Literature Analysis and Retrieval System OnLINE

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