Dharmacon, Inc.

Ge Healthcare Dharmacon, Inc.

Barbara Robertson

Anastasia Khvorova

Devin Leake

William Marshall

Annaleen Vermeulen

Kathryn Robinson

Christina Yamada

Anja Smith

William S Marshall

Scott Baskerville

Yuriy Fedorov

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.

Duplex oligonucleotides with enhanced functionality in gene regulation

The disclosure provides methods for inhibiting the activity of a miRNA cluster in a cell, and also for screening a cell for a phenotype(s) of interest resulting from inhibition of a miRNA cluster. The methods use a cluster pool which comprises at least one miRNA inhibitor specific for each miRNA in the miRNA cluster. MiRNA inhibitors are described that induce apoptosis in breast cancer cells and hence are useful in the treatment of breast cancer. The disclosure also provides pharmaceutical compositions which are useful for the treatment of breast cancer; methods for inducing the nuclear translocation of NF-&#x3ba;B in a breast cancer cell; methods for inducing the nuclear translocation of c-Jun in a breast cancer cell; method for inhibiting the nuclear translocation of NF-&#x3ba;B in a breast cancer cell; and methods for providing prognostic medical information relating to breast cancer progression.

Screening of micro-RNA cluster inhibitor pools

A reverse transfection apparatus can be used for introducing siRNA into a cell to effect gene silencing. Such an apparatus can include a well plate having a well configured for transfecting cells. The well can include a substantially dry gene silencing composition that has at least a first siRNA which silences a first target gene. The gene silencing composition can be configured such that the at least first siRNA is capable of being solubilized or suspended in an aqueous medium in an amount sufficient for transfecting cells in the well. Additionally, the at least first siRNA can include a modification or a conjugate. The reverse transfection apparatus can be provided as a kit or system that additionally includes cells, polynucleotide carriers, reverse transfection reagents, and the like.

Apparatus and system having dry gene silencing compositions

A reverse transfection apparatus can be used for introducing siRNA into a cell to effect gene silencing. Such an apparatus can include a well plate having a well configured for transfecting cells. The well can include a substantially dry gene silencing composition that has at least two siRNAs which silences at least a first target gene. The gene silencing composition can be configured such that the at least two siRNAs are each capable of being solubilized or suspended in an aqueous medium in an amount sufficient for transfecting cells in the well. Additionally, the siRNAs can include a hairpin structure, modification, or a conjugate. Also, the at least siRNAs can be rationally designed. The reverse transfection apparatus can be provided as a kit or system that additionally includes cells, polynucleotide carriers, reverse transfection reagents, and the like.

Apparatus and system having dry gene silencing pools

A method of determining a cellular response to a biological agent can be preformed in the presence of gene silencing. Such a method can include the use of siRNA in order to silence various genes in the cell in order to monitor the cellular response to the biological agent when a gene has been silenced. Accordingly, the response of a cell having a silenced gene to a biological agent can be indicative of which genes may be responsible for normal or abnormal cellular responses to various synthetic and natural biological agents such as active agents or pathogens.

Growing community of inventors

Boulder, CO, United States of America

Barbara Robertson