Abstract: The present invention provides compositions and methods for treating cutaneous T-cell lymphoma (CTCL) with intralesional administration of one or more miR-155 inhibitors. In certain embodiments, the intralesional administration of one or more oligonucleotide inhibitors of miR-155 reduces the redness, thickness, height, scaling, and/or surface area of one or more untreated lesions on the skin of said subject.

Abstract: The present invention relates to oligonucleotides with base modified nucleosides for enhancement of binding affinity.

Abstract: Disclosed are lipophilic polynucleotide conjugates including polynucleotide-cholesterol conjugates and methods of delivering therapeutic polynucleotides to a mammalian cell or patient in need of treatment using said conjugates. The disclosure further provides methods of synthesizing the lipophilic polynucleotide conjugates. The conjugates are designed to mimic or target cellular miRNAs. The lipophilic moiety, such as cholesterol or cholesterol derivative, is spaced from the polynucleotide by a substantially linear hydrocarbon group. Due to an absence of significantly polar groups and/or exchangeable protons in the vicinity of the lipophilic moiety, the interaction between the lipophilic moiety and cell membranes is enhanced to provide for efficient entry into cells.

Abstract: The invention provides chemically modified oligonucleotides capable of inhibiting the expression (e.g., abundance) of miR-208 family miRNAs, including miR-208a, miR-208b, and/or miR-499. The invention provides in some embodiments, oligonucleotides capable of inhibiting, in a specific fashion, the expression or abundance of each of miR-208a, miR-208b, and miR-499. The invention further provides pharmaceutical compositions comprising the oligonucleotides, and methods of treating patients having conditions or disorders relating to or involving a miR-208 family miRNA, such as a cardiovascular condition. In various embodiments, the oligonucleotides provide advantages in one or more of potency, efficiency of delivery, target specificity, toxicity, and/or stability.

Abstract: The present invention provides polynucleotides having chemistry patterns that provide for improved stability, potency, and/or toxicity relative to their use as miRNA inhibitors or miRNA mimetics. The invention further provides pharmaceutical compositions and formulations comprising the polynucleotides, and methods for treating patients having a condition associated with miRNA or mRNA expression.

Abstract: The invention provides chemically modified oligonucleotides capable of inhibiting the expression (e.g., abundance) of miR-208 family miRNAs, including miR-208a, miR-208b, and/or miR-499. The invention provides in some embodiments, oligonucleotides capable of inhibiting, in a specific fashion, the expression or abundance of each of miR-208a, miR-208b, and miR-499. The invention further provides pharmaceutical compositions comprising the oligonucleotides, and methods of treating patients having conditions or disorders relating to or involving a miR-208 family miRNA, such as a cardiovascular condition. In various embodiments, the oligonucleotides provide advantages in one or more of potency, efficiency of delivery, target specificity, toxicity, and/or stability.

Abstract: The present invention relates to oligonucleotides with base modified nucleosides for enhancement of binding affinity.

Abstract: Compositions, kits, systems, equipment, and protocols utilize synthetic siRNA having a delivery facilitating moiety in improved bioprocesses that enhance the production of biomaterials. The siRNA can target genes associated with the following: 1) deleterious vector derived genes; 2) genes that confer non-optimal growth or differentiation properties to the cells; 3) genes that can influence heterogeneity or post-translational modification pattern of the desirable gene product; 4) genes that highly express non-desired proteins; 5) genes that express proteins which interfere with purification of the desired protein; and 6) other genes that can interfere with the bioprocess.

Abstract: The invention provides chemically modified oligonucleotides capable of inhibiting the expression (e.g., abundance) of miR-208 family miRNAs, including miR-208a, miR-208b, and/or miR-499. The invention provides in some embodiments, oligonucleotides capable of inhibiting, in a specific fashion, the expression or abundance of each of miR-208a, miR-208b, and miR-499. The invention further provides pharmaceutical compositions comprising the oligonucleotides, and methods of treating patients having conditions or disorders relating to or involving a miR-208 family miRNA, such as a cardiovascular condition. In various embodiments, the oligonucleotides provide advantages in one or more of potency, efficiency of delivery, target specificity, toxicity, and/or stability.

Abstract: The present invention provides polynucleotides having chemistry patterns that provide for improved stability, potency, and/or toxicity relative to their use as miRNA inhibitors or miRNA mimetics. The invention further provides pharmaceutical compositions and formulations comprising the polynucleotides, and methods for treating patients having a condition associated with miRNA or mRNA expression.

Abstract: Disclosed are lipophilic polynucleotide conjugates including polynucleotide-cholesterol conjugates and methods of delivering therapeutic polynucleotides to a mammalian cell or patient in need of treatment using said conjugates. The disclosure further provides methods of synthesizing the lipophilic polynucleotide conjugates. The conjugates are designed to mimic or target cellular miRNAs. The lipophilic moiety, such as cholesterol or cholesterol derivative, is spaced from the polynucleotide by a substantially linear hydrocarbon group. Due to an absence of significantly polar groups and/or exchangeable protons in the vicinity of the lipophilic moiety, the interaction between the lipophilic moiety and cell membranes is enhanced to provide for efficient entry into cells.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: Compositions, kits, systems, equipment, and protocols utilize synthetic siRNA having a delivery facilitating moiety in improved bioprocesses that enhance the production of biomaterials. The siRNA can target genes associated with the following: 1) deleterious vector derived genes; 2) genes that confer non-optimal growth or differentiation properties to the cells; 3) genes that can influence heterogeneity or post-translational modification pattern of the desirable gene product; 4) genes that highly express non-desired proteins; 5) genes that express proteins which interfere with purification of the desired protein; and 6) other genes that can interfere with the bioprocess.

Abstract: The present invention concerns therapeutic agents that antagonize the activity of glucagon. In accordance with the present invention, the compounds of the invention comprise: a. a glucagon antagonist domain, preferably the amino acid sequence of SEQ ID NO: 7, or sequences derived therefrom by phage display, RNA-peptide screening, or the other techniques; and b. a vehicle, such as a polymer (e.g., PEG or dextran) or an Fc domain, which is preferred; wherein the vehicle is covalently attached to the glucagon antagonist domain. The vehicle and the glucagon antagonist domain may be linked through the N- or C-terminus of the glucagon antagonist domain. The preferred vehicle is an Fc domain, and the preferred Fc domain is an IgG Fc domain.

Abstract: The present invention concerns therapeutic agents that antagonize the activity of glucagon.

Abstract: The present invention concerns therapeutic agents that modulate the activity of CT receptor.

Abstract: The present invention describes a method for the inhibition of reverse transcriptase by contacting said reverse transcriptase with oligonucleotides having have at least one phosphorodithioate internucleotide linkage of the formula ##STR1## within the phosphorus backbone of the oligonucleotide.

Abstract: Oligonucleotides having at least one phosphorodithioate internucleotide linkage. Phosphorodithioate oligonucleotides exhibit stronger antiviral activity than the corresponding phoshorothioate derivatives.