Large-scale economic synthesis of antisense phosphorothioate analogues of DNA for preclinical investigations.
Identifieur interne : 004996 ( Main/Exploration ); précédent : 004995; suivant : 004997Large-scale economic synthesis of antisense phosphorothioate analogues of DNA for preclinical investigations.
Auteurs : T. Geiser [États-Unis]Source :
- Annals of the New York Academy of Sciences [ 0077-8923 ] ; 1990.
Descripteurs français
- KwdFr :
- MESH :
- pharmacologie : ADN, Antiviraux, Oligonucléotides antisens.
- synthèse chimique : ADN, Antiviraux, Oligonucléotides antisens.
- VIH-1 (Virus de l'Immunodéficience Humaine de type 1).
English descriptors
- KwdEn :
- MESH :
- chemical , chemical synthesis : Antiviral Agents, DNA, Oligonucleotides, Antisense.
- chemical , pharmacology : Antiviral Agents, DNA, Oligonucleotides, Antisense.
- drug effects : HIV-1.
Abstract
The therapeutic potential of antisense oligonucleotides will heavily depend on a balance of two factors: pharmacologic effectiveness and cost of production. Pharmacologic optimization will be achieved to a limited degree in in vitro systems, but substantial progress can only be made in the context of appropriate in vivo models. The quantities of synthetic oligonucleotides required for modest in vivo testing are several thousandfold greater than can be produced by conventional DNA synthesis technology and 10(5)-10(7)-fold greater for preclinical and clinical evaluation. Cost-effective synthesis and purification cannot be achieved by extrapolating current technologies to scales commensurate with these quantities. Recent interest in anti-HIV (anti-rev) phosphorothioate analogues of DNA (approximately 28-mers) has prompted us to develop scale-up methodology for routinely producing gram amounts of such analogues. These results and considerations given to producing clinical and commercial quantities were discussed.
DOI: 10.1111/j.1749-6632.1990.tb17838.x
PubMed: 2078018
Affiliations:
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Le document en format XML
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Geiser</name><affiliation wicri:level="2"><nlm:affiliation>Applied Biosystems, Inc., Foster City, California 94404.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Californie</region></placeName><wicri:cityArea>Applied Biosystems, Inc., Foster City</wicri:cityArea></affiliation></author></analytic><series><title level="j">Annals of the New York Academy of Sciences</title><idno type="ISSN">0077-8923</idno><imprint><date when="1990" type="published">1990</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Antiviral Agents (chemical synthesis)</term><term>Antiviral Agents (pharmacology)</term><term>DNA (chemical synthesis)</term><term>DNA (pharmacology)</term><term>HIV-1 (drug effects)</term><term>Oligonucleotides, Antisense (chemical synthesis)</term><term>Oligonucleotides, Antisense (pharmacology)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>ADN (pharmacologie)</term><term>ADN (synthèse chimique)</term><term>Antiviraux (pharmacologie)</term><term>Antiviraux (synthèse chimique)</term><term>Oligonucléotides antisens (pharmacologie)</term><term>Oligonucléotides antisens (synthèse chimique)</term><term>VIH-1 (Virus de l'Immunodéficience Humaine de type 1) ()</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemical synthesis" xml:lang="en"><term>Antiviral Agents</term><term>DNA</term><term>Oligonucleotides, Antisense</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Antiviral Agents</term><term>DNA</term><term>Oligonucleotides, Antisense</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>HIV-1</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>ADN</term><term>Antiviraux</term><term>Oligonucléotides antisens</term></keywords><keywords scheme="MESH" qualifier="synthèse chimique" xml:lang="fr"><term>ADN</term><term>Antiviraux</term><term>Oligonucléotides antisens</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>VIH-1 (Virus de l'Immunodéficience Humaine de type 1)</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The therapeutic potential of antisense oligonucleotides will heavily depend on a balance of two factors: pharmacologic effectiveness and cost of production. Pharmacologic optimization will be achieved to a limited degree in in vitro systems, but substantial progress can only be made in the context of appropriate in vivo models. The quantities of synthetic oligonucleotides required for modest in vivo testing are several thousandfold greater than can be produced by conventional DNA synthesis technology and 10(5)-10(7)-fold greater for preclinical and clinical evaluation. Cost-effective synthesis and purification cannot be achieved by extrapolating current technologies to scales commensurate with these quantities. Recent interest in anti-HIV (anti-rev) phosphorothioate analogues of DNA (approximately 28-mers) has prompted us to develop scale-up methodology for routinely producing gram amounts of such analogues. These results and considerations given to producing clinical and commercial quantities were discussed.</div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Californie</li></region></list><tree><country name="États-Unis"><region name="Californie"><name sortKey="Geiser, T" sort="Geiser, T" uniqKey="Geiser T" first="T" last="Geiser">T. Geiser</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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