DK2548962T3 - Sirna-sekvensuafhængige modifikationsformater til reduktion af off-target-fænotypeeffekter i RNAI og stabiliserede former deraf - Google Patents

Sirna-sekvensuafhængige modifikationsformater til reduktion af off-target-fænotypeeffekter i RNAI og stabiliserede former deraf Download PDF

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DK2548962T3
DK2548962T3 DK12189270.7T DK12189270T DK2548962T3 DK 2548962 T3 DK2548962 T3 DK 2548962T3 DK 12189270 T DK12189270 T DK 12189270T DK 2548962 T3 DK2548962 T3 DK 2548962T3
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sirna
sirnas
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Nitin Puri
Irudaya Charles
Susan Magdaleno
Alexander Vlassov
Chris Burnett
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Applied Biosystems Llc
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Claims (10)

1. Dobbeltstrenget RNA omfattende: et sense-olilgonukleotid med en længde på 17 til 30 nukleotider og omfattende: sekvensuafhængigt modifikationsformat (4): (4) 5' mp-Nx-m-m-Nq-nr 3' hvor p er 2, x er 10, r er 0, 1 eller 2, og q er et heltal, der repræsenterer længden af sense-oligonukleotidet minus (p+x+r+2); og et antisense-oligonukletoid med 17 til 30 nukleotider, en region med kontinuerlig komplementaritet til sense-nukleotidet med mindst 12 nukleotider, hvor antisense-oligonukleotidet yderligere har komplementaritet til mindst en del af target-mRNA, hvor hvert m er et 2'-OMe-modificeret nukleotid, hvert n uafhængigt er et deoxynukleotid, modificeret nukleotid eller ribonu-kleotid og er et overhængende nukleotid, og hvert N er uafhængigt et nukleotid, som ikke er et 2'-modificeret nukleotid.
2. Dobbeltstrenget RNA ifølge krav 1, hvor sense-oligonukleotidet og antisense-oligonukleotidet er kovalent bundne over et nukleotid-loop eller et lin-ker-loop for at danne et kort hairpin-oligonukleotid.
3. Dobbeltstrenget RNA ifølge krav 1, hvor hver 3'-ende af RNA'et uafhængigt har et et-, to- eller tre-nukleotidoverhæng, og/eller hvor en 5'-ende er yderligere derivatiseret med en fosfat-, C-M2-alkyl-, C-M2-alkylamin-, C-M2-alkenyl-, C-M2-alkynyl-, Ci-i2-cycloalkyl-, Ci-i2-aralkyl-, aryl-, acyl- eller silyl-substituent.
4. Dobbeltstrenget RNA ifølge krav 1, hvor mindst en internukleosidbinding er en anden binding end en fosfodiester-internukleosid-binding.
5. Dobbeltstrenget RNA ifølge krav 1, hvor det kemisk syntetiserede RNA yderligere er forbundet med en cellerettet ligand.
6. Kit omfattende det dobbeltstrengede RNA ifølge krav 1 og en transfek-tionsagens.
7. Dobbeltstrenget RNA ifølge krav 1 til brug som medikament.
8. Dobbeltstrenget RNA ifølge krav 1, hvor antisense-oligonukleotidet omfatter to 3'-overhængende modificerede nu-kleotider, og hvert modificeret nukleotid uafhængigt er et 2'-OMe-modificeret nukleotid.
9. Dobbeltstrenget RNA ifølge krav 8, hvor mindst en af de 3'-tredjesidste og 3'-fjerdesidste positioner for sense-oligonukleotidet er et 2'-OMe modificeret nukleotid.
10. Dobbeltstrenget RNA ifølge krav 8, hvor når længden er 17 nukleotider, er mindst en af positionerne 2 og 3 i antisense-oligonukleotidet et 2'-modificeret nukleotid, når længden er 18 nukleotider, er mindst en af positionerne 2, 3 og 4 i antisense-oligonukleotidet et 2'-modificeret nukleotid, når længden er 19 nukleotider, er mindst en af positionerne 2, 3, 4 og 5 i antisense-oligonukleotidet et 2'-modificeret nukleotid, når længden er 20 nukleotider, er mindst en af positionerne 2, 3, 4, 5 og 6 i antisense-oligonukleotidet et 2'-modificeret nukleotid, og når længden er 21-30 nukleotider, er mindst en af positionerne 2, 3, 4, 5, 6 og 7 for antisense-oligonukleotidet et 2'-modificeret nukleotid, hvor det 2'-modificerede nukleotid er et 2'-OMe-modificeret nukleotid.
DK12189270.7T 2007-09-19 2008-09-17 Sirna-sekvensuafhængige modifikationsformater til reduktion af off-target-fænotypeeffekter i RNAI og stabiliserede former deraf DK2548962T3 (da)

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US97354807P 2007-09-19 2007-09-19
EP08831316.8A EP2195428B1 (en) 2007-09-19 2008-09-17 SiRNA SEQUENCE-INDEPENDENT MODIFICATION FORMATS FOR REDUCING OFF-TARGET PHENOTYPIC EFFECTS IN RNAi, AND STABILIZED FORMS THEREOF

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