FORSBACH, ALEXANDRA,VOLLMER, JOERG,LIPFORD, GRAYSON B.
申请号：
ES06838257
公开号：
ES2536103T3
申请日:
2006.11.22
申请国别(地区):
ES
年份:
2015
代理人:
摘要：
A method for stimulating the production of a proinflammatory cytokine selected from TNF-alpha and IL-12 comprising: contacting a cell expressing TLR8 in vitro with an RNA oligonucleotide (ORN) comprising: NU-R1-R2, in where N is a ribonucleotide and N does not include a U, U is uracil or a derivative thereof, and R is a ribonucleotide in which at least one of R1 and R2 is adenosine (A) or cytosine (C) or derivatives of the same and in which R is not U unless NU-R1-R2 includes at least two A, in which the ORN is selected from: GCCACCGAGCCGAAUAUACC SEQ ID NO: 11； AUAUAUAUAUAUAUAUAUAU SEQ ID NO: 12； UUAUUAUUAUUAUUAUUAUU SEQ ID NO: 13； AAUAAUAAUAAUAAUAAUAA SEQ ID NO: 16； AAAUAAAUAAAUAAAUAAAU SEQ ID NO: 17； AAAAUAAAAUAAAAUAAAAU SEQ ID NO: 18； CUACUACUACUACUACUACU SEQ ID NO: 24； UUAUUAU SEQ ID NO: 30； UAUAUAU SEQ ID NO: 33； CCGAGCCGCAUAUCCC SEQ ID NO: 36； CCGAGCCGCUAUACCC SEQ ID NO: 37； CCGAGCCAUAUAUCCC SEQ ID NO: 38； CCGAGCCAUAUAUAUC SEQ ID NO: 39； CCGAGCCGAAUAACCC SEQ ID NO: 40； CCGAGCCGCAUAACCC SEQ ID NO: 41； CCGAGCCGAAUACCCC SEQ ID NO: 42； CCGAGCCGCCUAACCC SEQ ID NO: 43； CCGAGCCGAAUCCCCC SEQ ID NO: 44； CCGAGCCGCAUACCCC SEQ ID NO: 45； CCGAGCCGCAUCCCCC SEQ ID NO: 46； CCGAGCCGCCUACCCC SEQ ID NO: 47； CCGAGCCGCAUUACCC SEQ ID NO: 48； CCGAGCCGCUAUCCCC SEQ ID NO: 55； CCGAGCCGAAUGUACC SEQ ID NO: 63； CCGAGCCGAUAUUACC SEQ ID NO: 65； CCGAGCCGAAGGUACC SEQ ID NO: 82； CCGAGCCGAAGGUGCC SEQ ID NO: 83； CCGAGCCGAAGCUCCC SEQ ID NO: 84； CCGAGCCGAAGAUACC SEQ ID NO: 85； CCGAGCCGAAGCUACC SEQ ID NO: 87； and CCGAGCCGAAGCUGCC SEQ ID NO: 88； in which the ORN optionally includes at least one modification in its structure； in an amount effective to stimulate the production of proinflammatory cytokines and in which the production of IFN-α in response to the ORN is not significantly induced in relation to the background； and also in which the ORN is complexing with N- [1- (2,3-dioleoyloxy) propyl] -N, N, N-trimethylammoniomethyl sulfate (DOTAP).Un procedimiento para estimular la producción de una ci
