Sudhir Agrawal's Antisense Therapeutics PDF

By Sudhir Agrawal

ISBN-10: 0896033058

ISBN-13: 9780896033054

Major researchers provide an authoritative survey and research of the newest findings at the quick improvement of antisense oligonucleotides healing and their program in quite a few in vivo version structures. The book's high-profile individuals offer well timed money owed in their state of the art ideas, discussing such themes because the synthesis and purification of oligonucleotides, their choice for a selected gene aim, diverse equipment of management, and using a variety of mobilephone traces and phone tradition structures. additionally they learn questions of mobile uptake, in vitro organic job, in vivo organic task, the pharmacology and pharmacokinetics of oligonucleotides, and the applying of oligonucleotides to the vital frightened method.

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The pharmacokmetics of these compounds demonstrates that once a day or every other day dosing is feasible. 05-5 mg/kg will produce sign&ant effects. Given these data, and the recent dramatic reductions m cost of large-scale synthesis of phosphorothioates (A. Scozzarr, unpublished results), this class of compounds holds great promise for commercial success. Phosphorothioates represent only the first class of antisense compounds. There is substantial scope for improvement through medicinal chemistry, and many laboratories have demonstrated that novel antisense oligonucleotide ana- An tisense Therapeubcs 41 logs can have improved properties (reviewed in refs.

Results represent the mean f SD (N = 5) Several experiments were performed to address the mechanism by which the ICAM- 1 antlsense ohgonucleotlde inhibited leukocyte migration. There was no slgmficant effect of the oligonucleotide on hematology parameters, including leukocyte number or differential leukocyte counts. Therefore, the decrease m leukocyte emlgratlon was not the result of the ohgonucleotide producing a neutropemc state. Cells that infiltrated the graft were predominately neutrophlls and monocytes (data not shown).

To test whether the murme-specific ICAM- 1 phosphorothloate antisense ohgonucleotide, ISIS 3082, would inhibit leukocyte migration into inflamed tissues, we implanted carrageenan-soaked polyester sponges mto the subcutaneous space on the back of mice. Carrageenan, an algal polysaccharide, has been widely used to induce inflammation at the site of admmistratlon and 1s a standard test for anti-inflammatory compounds (62). Hallmarks of carrageenaninduced inflammation include a marked edematous reaction and leukocyte influx.

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Antisense Therapeutics by Sudhir Agrawal

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