A method for treating cancer in a subject in need thereof includes administering to cancer cells of the subject an agent effective to modulate the level of DNMT1-associated RNA and/or the interaction of DNMT1-associated RNA and DNMT1 in the cancer cells of the subject. Embodiments described herein relate to RNAs (e.g., IncRNAs) associated with DNA methyltransferase 1 (DNMTI-associated RNA) in human cancer cells, methods and compositions of modulating the levels of DNMTI-associated RNA and/or the interaction of DNMT1-associated RNA and DNMT1 in cancer cells of the subject to treat cancer cells or a subject in need thereof, and/or methods of measuring the expression profile of DNMT1 associated RNA to determine whether the subject has cancer or an increased risk of cancer and/or the efficacy of a therapeutic regimen agent.

The present invention is a method for measuring the amount of at least one molecule in a biological sample, the method comprising a) combining the sample, or a derivative thereof, with one or more aptamers and allowing one or more molecules in the sample to bind to the aptamer(s); b) separating bound from unbound molecules; and c) quantifying the molecule(s) bound to the or each aptamer, wherein quantification of the bound molecule(s) is carried out by sequencing at least part of the or each aptamer. Uses of and products derived from the method are also contemplated.

The present invention concerns methods and compositions regarding one or more microRNAs or variants thereof that are provided to an individual for a variety of medical treatments, including sensitization to cancer therapy or prevention of a cancer to become sensitized to a cancer therapy. In specific embodiments, the microRNAs include miR-520a (including at least miR-520a-3p and miR-520-5p), miR-520g, miR-520h, and functional variants thereof. In some embodiments, the cancer is ovarian cancer, and in particular embodiments, the cancer therapy is platinum-based chemotherapy.

Compositions and methods of treating an inflammatory disease in a subject are provided. Accordingly there is provided a method comprising administering to the subject a therapeutically effective amount of an agent which selectively inhibits activity and/or expression of iron regulatory protein (IRP) 1 and not IRP2, thereby treating the inflammatory disease in the subject. Also provided is a pharmaceutical composition comprising, as an active ingredient, an agent which selectively inhibits activity and/or expression of IRP1 and not IRP2, and a pharmaceutically acceptable carrier or excipient. Also provided are methods of identifying an agent that selectively modulates an activity of an IRP member of an IRP family of polypeptides and not of an additional IRP member of said IRP family of polypeptides.

Provided are compositions comprising an oligonucleotide that targets Thymic stromal lymphopoietin (TSLP). The oligonucleotide may include a small interfering RNA (siRNA) or an antisense oligonucleotide (ASO). Also provided herein are methods of treating an airway disorder by providing an oligonucleotide that targets TSLP to a subject in need thereof. In some embodiments, the oligonucleotide targeting is specific for a long isoform of TSLP (1fTSLP).

The specification provides methods for introducing a desired genetic change in a nucleotide sequence using a double-strand break (DSB)-inducing genome editing system, the method comprising: identifying one or more available cut sites in a nucleotide sequence; analyzing the nucleotide sequence and available cut sites with a computational model to identify the optimal cut site for introducing the desired genetic change into the nucleotide sequence; and contacting the nucleotide sequence with a DSB-inducing genome editing system, thereby introducing the desired genetic change in the nucleotide sequence at the cut site.

A system for selecting CRISPR guides for knocking out one or more target genes in a target cell from a multiplicity of candidate guides comprises a memory and a processor. The processor determines whether the candidate guide meets a plurality of thresholds. The thresholds are associated with: a transcript support level; targeting a consensus sequence of a target gene; which exon of the target gene is targeted; targeting of a primary transcript, targeting of a common isoform; a precomputed prediction of editing outcomes; mapping to an expressed sequence; fraction of gene expression attributable to targeted transcripts; a common SNP overlap threshold; which exon of the target gene is targeted; overlap of a selected guide; predicted frameshift percentage; maximum and minimum GC content; off target score; where a coding sequence is targeted. In response to meeting the thresholds, the processor selects the candidate guide as a selected CRISPR guide.

The present invention includes compositions and methods for treating an autoimmune disorder or a cancer in a subject in need thereof, the method comprising: administering an effective amount of a composition comprising an oligonucleotide that specifically binds a complementary sequence of the Interleukin-7 receptor (IL7R) pre-mRNA that influences splicing of exon 6, wherein the SM-ASO increases or decreases inclusion of exon 6 in IL7R pre-mRNAs and respectively decreases or increases expression of the soluble isoform of IL7R (sIL7R). In certain embodiments, the oligonucleotide is an antisense oligonucleotide (ASO), or a splice-modulating antisense oligonucleotide (SM-ASO).

The present disclosure provides antisense oligonucleotides, compositions, and methods that target a LIPA intron flanking exon 8, thereby modulating splicing of LIPA pre-mRNA to increase the level of LIPA mRNA molecules having exon 8, e.g., to provide a therapy for Wolman Disease or Cholesteryl Ester Storage Disease. The present disclosure provides an antisense oligonucleotide including a nucleobase sequence at least 70% complementary to a LIPA pre-mRNA target sequence in a 5′-flanking intron, a 3′-flanking intron, or a combination of exon 8 and the 5′-flanking or 3′-flanking intron.

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 TTR.