摘要:
Interative, preferably computer based iterative processes for generating synthetic compounds with desired physical, chemical and/or bioactive properties, i.e., active compounds, are provided. During iterations of the processes, a target nucleic acid sequence is provided or selected, and a library of candidate nucleobase sequences is generated in silico according to defined criteria. A “virtual” oligonucleotide chemistry is chosen and a library of virtual oligonucleotide compounds having the selected nucleobase sequences is generated. These virtual compounds are reviewed and compounds predicted to have particular properties are selected. The selected compounds are robotically synthesized and are preferably robotically assayed for a desired physical, chemical or biological activity. Active compounds are thus generated and, at the same time, preferred sequences and regions of the target nucleic acid that are amenable to oligonucleotide or sequence-based modulation are identified.
摘要:
Compounds, compositions and methods are provided for modulating the expression of Interleukin 12 p35 subunit. The compositions comprise chemically modified antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding Interleukin 12 p35 subunit. Methods of using these compounds for modulation of Interleukin 12 p35 subunit expression and for treatment of diseases associated with expression of Interleukin 12 p35 subunit are provided.
摘要:
Compounds, compositions and methods are provided for modulating the RNAi pathway. The compositions comprise oligonucleotides, targeted to nucleic acid molecules encoding EIF2C2. Methods of using these compounds for modulation of RNA interference as well as EIF2C2 expression and for diagnosis and treatment of disease associated with expression of EIF2C2 are provided. Also provided are compounds, compositions and methods for modulating the expression of DDX36. The compositions comprise oligonucleotides, targeted to nucleic acid encoding DDX36. Methods of using these compounds for modulation of DDX36 expression and for diagnosis and treatment of diseases and conditions associated with expression of DDX36 are provided.
摘要:
Compounds, compositions and methods are provided for modulating the expression and function of small non-coding RNAs. The compositions comprise oligomeric compounds, targeted to small non-coding RNAs. Methods of using these compounds for modulation of small non-coding RNAs as well as downstream targets of these RNAs and for diagnosis and treatment of disease associated with small non-coding RNAs are also provided.
摘要:
Compounds, compositions and methods are provided for modulating the expression of splice variants or products. The compositions comprise oligonucleotides, targeted to nucleic acid encoding splice variants or products. Methods of using these compounds for modulation of expression of splice variants or products and for diagnosis and treatment of disease associated with expression of splice variants or products are provided.
摘要:
Interative, preferably computer based iterative processes for generating synthetic compounds with desired physical, chemical and/or bioactive properties, i.e., active compounds, are provided. During iterations of the processes, a target nucleic acid sequence is provided or selected, and a library of candidate nucleobase sequences is generated in silico according to defined criteria. A “virtual” oligonucleotide chemistry is chosen and a library of virtual oligonucleotide compounds having the selected nucleobase sequences is generated. These virtual compounds are reviewed and compounds predicted to have particular properties are selected. The selected compounds are robotically synthesized and are preferably robotically assayed for a desired physical, chemical or biological activity. Active compounds are thus generated and, at the same time, preferred sequences and regions of the target nucleic acid that are amenable to oligonucleotide or sequence-based modulation are identified.
摘要:
Methods are provided for the identification of compounds that selectively modulate epigenetic changes in gene expression. Compounds, compositions, kits or assays devices, and methods are provided for modulating the expression, endogenous levels or the function of small non-coding RNAs cognate to or transcribed by heterochromatic regions subject to epigenetic regulation (i.e., promoters, enhancers, centromeres, telomeres, origins of DNA replication, imprinted loci, or loci marked by dosage-compensation), and for modulating the formation or function of heterochromatin in cells, tissues or animals.
摘要:
Methods useful for the determination of oligomers which have specific activity for a target molecule from a pool of primarily randomly assembled oligomers are provided. The disclosed methods involve repeated syntheses of increasingly simplified sets of oligomers coupled with selection procedures for determining oligomers having the highest activity. Freedom from the use of enzymes allows the application of these methods to any molecules which can be oligomerized in a controlled fashion.
摘要:
Provided herein are methods for determining potency of RNAi agents. Such methods include, but are not limited to, cell-based and cell-free assays that measure binding of an RNAi agent with Ago2 or that measure Ago2 activity in the presence of such RNAi agents. Also provided are assays that determine potency of RNAi agents by assessing their ability to compete with other RNAi agents, including control RNAi agents, for binding and/or activation of Ago2.
摘要:
Antisense compounds, compositions and methods are provided for modulating the expression of MyD88. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding MyD88. Methods of using these compounds for modulation of MyD88 expression and for treatment of diseases associated with expression of MyD88 are provided.