发明名称 |
Compositions and methods for immunostimulatory RNA oligonucleotides |
摘要 |
The present invention provides 4-nucleotide (4mer) RNA motifs that confer immunostimulatory activity, in particular, IL-12-inducing activity to a single-stranded RNA oligonucleotide. The present invention also provides single-stranded RNA oligonucleotides, including antisense RNA, with high or low immunostimulatory activity. The present invention further provides the use of the RNA oligonucleotides of the invention for therapeutic purposes. |
申请公布号 |
US8815503(B2) |
申请公布日期 |
2014.08.26 |
申请号 |
US200612066906 |
申请日期 |
2006.09.14 |
申请人 |
Rheinische Friedrich-Wilhelms-Universitat Bonn |
发明人 |
Hartmann Gunther;Hornung Veit |
分类号 |
C12Q1/68;A61K39/39;C07H21/02;C07H21/04;A61K38/20 |
主分类号 |
C12Q1/68 |
代理机构 |
Leydig, Voit & Mayer, Ltd. |
代理人 |
Leydig, Voit & Mayer, Ltd. |
主权项 |
1. A method for preparing an antisense RNA oligonucleotide having gene silencing activity and high IL-12 inducing activity, comprising the steps of:
(a) identifying all potential antisense sequences between 18 and 50 nucleotides in length, for a target mRNA; (b) identifying antisense sequences that have gene silencing activity; (c) identifying antisense RNA sequences from those among identified in step (b) which have an IL-12 score of at least 8.4064×n+66.958, wherein the IL-12 score is assigned according to the method comprising the steps of:
(i) identifying all possible 3-nucleotide (3mer) motifs contained in the oligonucleotide;(ii) assigning an IL-12 point score for each individual 3mer motif
(A) for a 3mer motif which appears in Table 5, assign an IL-12 point score according to Table 5;(B) for a 3mer motif which does not appear in Table 5, assign an IL-12 point score of 0;(iii) assigning the sum of the IL-12 point scores of individual 3mer motifs as the IL-12 score of the oligonucleotide; and wherein n is the length of the sequence and n is between 18 and 50; (d) decreasing the IL-12 score threshold by 1 if no antisense sequence is identified in step (c), until at least one antisense sequence is identified; (e) preparing the antisense RNA identified in step (c) or (d); and (f) optionally testing the gene silencing and/or the IL-12 inducing activity of the antisense prepared in (e). |
地址 |
Bonn DE |