摘要:
The present invention relates to RNAi constructs with improved tissue and cellular uptake characteristics and methods of use of these compounds in dermal applications.
摘要:
Efficient sequence specific gene silencing is possible through the use of siRNA technology. By selecting particular siRNAs by rational design, one can maximize the generation of an effective gene silencing reagent, as well as methods for silencing genes. Methods, compositions, and kits generated through rational design of siRNAs are disclosed including those directed to nucleotide sequences for KDR.
摘要:
The invention relates to various PCSK9 RNAi constructs with gene silencing activities, and uses thereof The construct has a double-stranded region of 19-49 nucleotides, preferably 25, 26, or 27 nucleotides, and preferably blunt-ended The construct has selective minimal modifications to confer an optimal balance of biological activity, toxicity, stability, and target gene specificity The sense strand may be modified such that the construct is not cleaved by Dicer or other RNAse III, and the entire length of the antisense strand is loaded into RISC In addition, the antisense strand may also be modified by 2′-O-methyl groups at the 2nd 5′-end nucleotide to greatly reduce off-target silencing The constructs of the invention largely avoid the interferon response and sequence-independent apoptosis in mammalian cells, exhibits better serum stability, and enhanced target specificity.
摘要翻译:本发明涉及具有基因沉默活性的各种PCSK9 RNAi构建体及其用途。该构建体具有19-49个核苷酸,优选25,26或27个核苷酸的双链区域,优选为平端。该构建体具有选择性最小修饰 赋予生物活性,毒性,稳定性和靶基因特异性的最佳平衡有义链可以被修饰,使得构建体不被切丝虫或其他RNA酶III切割,并且反义链的整个长度被加载到RISC In 此外,反义链也可以在第二个5'-末端核苷酸处被2'-O-甲基修饰,以大大减少脱靶沉默本发明的构建体大大地避免了哺乳动物细胞中的干扰素应答和序列无关的凋亡 ,表现出更好的血清稳定性和增强的靶特异性。
摘要:
Efficient sequence specific gene silencing is possible through the use of siRNA technology. By selecting particular siRNAs by rational design, one can maximize the generation of an effective gene silencing reagent, as well as methods for silencing genes. Methods, compositions, and kits generated through rational design of siRNAs are disclosed including those directed to nucleotide sequences for APOB.
摘要:
Efficient sequence specific gene silencing is possible through the use of siRNA technology. By selecting particular siRNAs by rational design, one can maximize the generation of an effective gene silencing reagent, as well as methods for silencing genes. Methods, compositions, and kits generated through rational design of siRNAs are disclosed including those directed to nucleotide sequences for MYD88.
摘要:
Disclosed are methods of enhancing functionality of duplex oligonucleotides and compositions made by the methods. The duplex oligonucleotides include siRNAs, miRNA mimics, and piRNA mimics which contain modified nucleotides and mismatches between the two strands of the molecule at specific nucleotide positions.
摘要:
Provided herein are duplex oligonucleotide complexes which can be administered to a cell, tissue or organism to silence a target gene without the aid of a transfection reagent(s). The duplex oligonucleotide complexes of the disclosure include a conjugate moiety that facilitates delivery to a cell, tissue or organism.
摘要:
Efficient sequence specific gene silencing is possible through the use of siRNA technology. By selecting particular siRNAs by rational design, one can maximize the generation of an effective gene silencing reagent, as well as methods for silencing genes. Methods, compositions, and kits generated through rational design of siRNAs are disclosed including those directed to nucleotide sequences for APOB.