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DK2009990T3 - Fremgangsmåder og sammensætninger relateret til adenoassocierede virusfagpartikler - Google Patents

Fremgangsmåder og sammensætninger relateret til adenoassocierede virusfagpartikler Download PDF

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DK2009990T3
DK2009990T3 DK07760348.8T DK07760348T DK2009990T3 DK 2009990 T3 DK2009990 T3 DK 2009990T3 DK 07760348 T DK07760348 T DK 07760348T DK 2009990 T3 DK2009990 T3 DK 2009990T3
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aavp
fluoro
gene
cells
uracil
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Mian Alauddin
Martin Trepel
Renata Pasqualini
Wadih Arap
Frank C Marini Iii
Juri Gelovani
Amin Hajitou
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Univ Texas
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    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
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Claims (13)

1. Adeno-associeret viral bakteriofagvektor (AAVP) omfattende et fag-DNA med en ekspressionskassetteinsertion, hvor ekspressionskassetten har to adeno-associeret virus (AAV) inverted terminal repeats, hvor AAVP'en omfatter et reportergen og et terapeutisk gen, hvilken AAVP er til anvendelse ved behandling og forebyggelse af en hyperproliferativ sygdom, hvor reportergenet er til vurdering af in situ-ekspression ved detektering af reportergenaktiviteten, hvor vurdering af AAVP-ekspression (a) omfatter at indgive et detekterbart mærke, der metaboliseres selektivt af en celle, der eksprimerer en AAVP-nukleinsyre, hvor mærket er udvalgt fra gruppen bestående af fluordeoxyglucose (FDG); 2'-fluor-2'deoxy-1-p-D-arabionofuranosyl-5-ethyl-uracil (FEAU); 5-[123l]-2'-fluor-5-iodo-1 β-D-arabinofuranosyl-uracil; 5-[124l]-2'-fluor-5-iodo-ip-D-arabinofuranosyl-uracil; 5-[131l]-2'-fluor-5-iodo-1 β-D-arabino-furanosyl-uracil, 5-[1sF]-2'-fluor-5-fluor-1-β-D-arabinofuranosyl-uracil; 2-[11l]- og 5-([11C]-methyl)-2'-fluor-5-methyl-1^-D-arabinofuranosyl-uracil; 2-[11C]-2'-fluor-5-ethyl-1^-D-arabinofuranosyl-uracil; 5-([11C]-ethyl)-2'-fluor-5-ethyl-1 -β-D-arabino-furanosyl-uracil; 5-(2-[1sF]-ethyl)-2'-fluor-5-(2-fluor-ethyl)-1^-D-arabinofuranosyl-uracil, 5-[123l]-2'-fluor-5-iodovinyl-1 -β-D-arabinofuranosyl-uracil; 5-[ 124l]-2'-fluor-5-iodovinyl-1 -β-D-arabinofuranosyl-uracil; 5-[131l]-2'-fluor-5-iodovinyl-1-β-D-arabino-furanosyl-uracil; 5- [123l]-2'-fluor-5-iodo-1 -β-D-ribofuranosyl-uracil; 5-[124l]-2'-fluor-5-iodo-1-β-D-ribofuranosyl-uracil; 5-[131l]-2'-fluor-5-iodo-1-β-D-ribofuranosyl-uracil; 5-[123l]-2'-fluor-5-iodovinyl-1 -β-D-ribofuranosyl-uracil; 5-[124l]-2'-fluor-5-iodovinyl-1-β-D-ribofuranosyl-uracil; 5-[131l]-2'-fluor-5-iodovinyl-1-β-D- ribofuranosyl-uracil; og 9-4-[18F]-fluor-3-(hydroxymethyl)butyl]guanin; og (b) udføres ved ikke-invasiv detektering af reporteren eller en aktivitet af reporteren, hvor reporteren er en kinase, der modificerer det detekterbare mærke, og hvor AAVP'en omfatter en del, der selektivt er målrettet et væv eller en celle, der skal behandles.
2. AAVP til anvendelse ifølge krav 1, hvor det terapeutiske gen også er reportergenet.
3. AAVP til anvendelse ifølge krav 1, hvor det terapeutiske gen koder for et prodrug-konverterende enzym.
4. AAVP til anvendelse ifølge krav 1, hvor delen er et capsidprotein kodet af AAVP'en, især hvor capsidproteinet er et rekombinant capsidprotein, hvilket rekombinante capsidprotein fortrinsvis omfatter et cyklisk eller lineært targeting-peptid.
5. AAVP til anvendelse ifølge krav 4, hvor targeting-peptidet selektivt binder en celle, der eksprimerer et integrin på celleoverfladen, især hvor integrinet er ανβ3- eller av35-integrin; hvor targeting-peptidet omfatter et RGD-motiv; eller hvor targeting-peptidet selektivt binder en celle, der eksprimerer en transferrinreceptor, især hvor peptidet omfatter en aminosyresekvens, der omfatter CRTIGPSVC.
6. AAVP til anvendelse ifølge krav 1, hvor den hyperproliferative sygdom er fibrosarkom, myosarkom, liposarkom, chondrosarkom, osteogent sarkom, chordom, angiosarkom, endotheliosarkom, lymphangiosarkom, lymphangio-endotheliosarkom, synoviom, mesotheliom, Ewings tumor, leiomyosarkom, rhabdomyosarkom, gastrisk cancer, øsofaguscancer, rektal cancer, pan-creascancer, ovariecancer, prostatacancer, livmoderkræft, hoved- og halscancer, hudcancer, hjernecancer, pladecellekarcinom, talgkirtelkarcinom, papillært karcinom, papillært adenokarcinom, cystadenokarcinom, medullært karcinom, bronkogent karcinom, renalcellekarcinom, hepatom, galdegangs-karcinom, koriokarcinom, seminom, embryonalt karcinom, Wilms tumor, livmoderhalskræft, testi kel kræft, småcellet lungekarcinom, ikke-småcellet lung-karcinom, blærekarcinom, epitelkarcinom, gliom, astrocytom, medullobla-stom, kraniofaryngeom, ependymom, pinealom, hemangioblastom, akustisk neurom, oligodendrogliom, meningiom, melanom, neuroblastom, retinobla-stom, leukæmi, lymfom eller Kaposis sarkom.
7. AAVP til anvendelse ifølge krav 1, hvor reportergenet er funktionelt forbundet med en vævs- eller celleselektiv promoter eller en vævs- eller cellespecifik promoter.
8. AAVP til anvendelse ifølge krav 1, hvor den terapeutiske AAVP koder for et andet terapeutisk gen, især hvor det andet terapeutiske gen er en tumor-suppressor, et inhibitorisk RNA, et inhibitorisk DNA eller et prodrug-konverterende enzym.
9. AAVP til anvendelse ifølge krav 1, hvor AAVP'en indføres i målvævets celler ved in vitro- eller in vivo-transfektion eller -transduktion.
10. AAVP til anvendelse ifølge krav 1, hvor substratet til reporteren er markeret med en radioisotop, der er egnet til billeddiagnostik med positronemissi-onstomografi, gammakamera eller SPECT (single-photon emission computed tomography), eller hvor substratet til reporteren er en forbindelse indeholdende en stabil isotop nuklid udvalgt fra gruppen bestående af 2H, 13C, 15N og 19F.
11. AAVP til anvendelse ifølge krav 1, hvor AAVP'en inkorporerer transkripti-onspromoteren og enhancer-elementer, hvilket sikrer vævsspecifik, transkrip-tionsfaktorspecifik eller signaltransduktionspecifik transkriptionsaktivering af coekspression af reportergen og terapeutisk gen.
12. AAVP til anvendelse ifølge krav 1, hvor det terapeutiske gen koder for et inhibitorisk RNA eller inhibitorisk DNA, især hvor det inhibitoriske RNA er et siRNA, et miRNA eller et antisense-RNA.
13. AAVP til anvendelse ifølge krav 12, hvor fagpartiklen yderligere omfatter en targeting-ligand.
DK07760348.8T 2006-04-07 2007-04-09 Fremgangsmåder og sammensætninger relateret til adenoassocierede virusfagpartikler DK2009990T3 (da)

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