Abstract: The present disclosure relates to a compound including a nucleic acid sequence conjugated to an anti-microRNA or a microRNA-mimic or a compound including a modified anti-microRNA sequence, compositions of such a compound, and method of treatment of a disease, and method of suppressing microRNA activity by the disclosed compound or composition.

Abstract: The present invention provides a method of treating a disease associated with elevated KRAS activity or expression in a subject, comprising suppressing KRAS expression in the subject by targeting an expression regulatory region of KRAS gene using a CRISPR-Guide Nucleotide Directed Modulation (GNDM). Also, provided is a CRISPR-GNDM system for suppressing KRAS expression comprising (a) a protein selected from the group consisting of dCas9 or dCpf1, a fusion protein of dCas9 or dCpf1 and Kruppel associated box (KRAB), and (b) a guide nucleotide targeting an expression regulatory region of KRAS gene.

Abstract: The present disclosure provides compositions which shown preferential targeting or delivery of a nucleic acid composition to a particular organ. In some embodiments, the composition comprises a steroid or sterol, an ionizable cationic lipid, a phospholipid, a PEG lipid, and a permanently cationic lipid which may be used to deliver a nucleic acid.

Abstract: The present technology relates, in part, to long double-stranded RNA (dsRNA) (e.g., 30 or more base pairs) that inhibits gene expression.

Abstract: Provided are compounds, methods, and pharmaceutical compositions for reducing the amount or activity of ATXN3 mRNA in a cell or animal, and in certain instances reducing the amount of Ataxin-3 protein in a cell or animal. Such compounds, methods, and pharmaceutical compositions are useful to prevent or ameliorate at least one symptom or hallmark of a neurodegenerative disease. Such symptoms and hallmarks include ataxia, neuropathy, and aggregate formation. Such neurodegenerative diseases include SCA3.

Abstract: The present disclosure provides nucleic acid compositions that incorporate one or more halouracil molecules. More specifically, the present disclosure reveals that the replacement of uracil nucleotides within a microRNA nucleotide sequence with a 5-halouracil increases the ability of the micro-RNA to inhibit cancer progression and tumorigenesis. As such, the present disclosure provides various nucleic acid (e.g., microRNA) compositions having 5-halouracil molecules incorporated in their nucleic acid sequences and methods for using the same. The present disclosure further provides pharmaceutical compositions comprising the modified nucleic acid compositions, and methods for treating cancers using the same.

Abstract: Polynucleotides, such as aptamers, comprising at least first one 5-position modified pyrimidine and at least one second 5-position modified pyrimidine are provided, wherein the first and second 5-position modified pyrimidines are different. Methods of selecting and using such polynucleotides, such as aptamers, are also provided.

Abstract: In some aspects, the disclosure provides methods for modulating mitochondrial transport of serine in a cell, the methods comprising modulating expression or activity of one or more sideroflexins. In some aspects, methods of identifying agents that modulate sideroflexin expression or activity are provided. In some aspects, methods of treating cancer are provided.

Abstract: The present invention relates to an expression control composition for controlling the expression of a duplicate gene or a method using the same. In addition, the present invention relates to a method of treating or improving a disease caused by gene duplication using the expression control composition for controlling the expression of a duplicate gene.

Abstract: Disclosed herein are methods of inhibiting nuclear pore complex assembly and inducing nuclear pore complex disassembly. Methods to screen for agents that inhibit nuclear pore assembly or induce nuclear pore complex disassembly are also disclosed.

Abstract: The present disclosure relates to genetically modified T cells comprising a transgene encoding an engineered antigen specific receptor, wherein expression of an endogenous gene selected from MNK1, MNK2, or both are inhibited in the genetically modified T cell in order to enhance central memory T cell subsets in cellular immunotherapy compositions.

Abstract: The present invention includes synthesis of polyethyleneimine800-EpoxyC8-22 (PEI800-C8-22) lipids, e.g., Polyethyleneimine800-EpoxyC16 (PEI800-C16), PEI12C16, PEI8C16, and PEI4C16 lipids, compositions and methods for transfecting primary leukocytes, myeloid cells, lymphoid cells, monocytes, macrophages and dendritic cells (DC) comprising a transfection complex comprising: one or more nanoparticles; and Polyethyleneimine800-EpoxyC16 (PEI800-C16), PEI12C16, PEI8C16, and PEI4C16 lipids complexed with one or more nucleic acids, such as, e.g., DNA, RNA, nucleic acid vectors, shRNA, miRNA, and RNAi on or about the nanoparticles.

Abstract: Provided herein are recombinant circular RNA (circRNA) molecules comprising an internal ribosome entry site (IRES) operably linked to a protein-coding nucleic acid sequence. The IRES includes at least one RNA secondary structure element; and a sequence region that is complementary to an 18S ribosomal RNA (rRNA). Methods of producing a protein in a cell using the recombinant circRNA molecules are also provided.

Abstract: The present embodiments provide methods, compounds, and compositions useful for inhibiting FOXP3 expression, which may be useful for treating, preventing, or ameliorating cancer.

Abstract: One aspect of the present invention relates to double-stranded RNA (dsRNA) agent capable of inhibiting the expression of a target gene. The sense strand of the dsRNA agent comprises at least one thermally destabilizing nucleotide, and at least one said thermally destabilizing nucleotide occurring at a site opposite to the seed region (positions 2-8) of the antisense strand; and the antisense strand of the dsRNA agent comprises. at least two modified nucleotides that provide the nucleotide a steric bulk that is less than or equal to the steric bulk of a 2?-OMe modification, wherein said modified nucleotides are separated by 11 nucleotides in length. Other aspects of the invention relates to pharmaceutical compositions comprising these dsRNA agents suitable for therapeutic use, and methods of inhibiting the expression of a target gene by administering these dsRNA agents, e.g., for the treatment of various disease conditions.

Abstract: Methods and compositions for modulating transforming growth factor-beta (TGF?) biological activity in a vertebrate subject in need thereof. The methods involve administering to the vertebrate subject an effective amount of a substance capable of modulating activity of LEMD3 in the vertebrate subject to thereby modulate TGF? biological activity in the vertebrate subject.

Abstract: Disclosed are nucleic acid oligomer compounds and to their use in compositions and methods for inhibiting proliferation, survival or viability of cancer cells including prostate, lung, pancreatic, breast, cervical and bone cancer cells.

Abstract: Provided herein, in some embodiments, are materials and methods for treating hemophilia A in a subject ex vivo or in vivo. Also provided herein, in some embodiments, are materials and methods for knocking in a coding sequence encoding a synthetic FVIII having a B domain substitute into a genome.

Abstract: RNAs, such as miRNA and siRNA, and their use in treating complement-mediated disorders, are described.

Abstract: In the present invention it is shown that the inactivation of the Pyk2 gene does not alter hippocampal development but prevents hippocampal-dependent memory tasks and LTP. Inventors clearly provide evidence for multiple roles of Pyk2 in spine morphology and postsynaptic structure. Thus, the inventors used direct overexpression of PYK2 by AAV-mediated gene transfer into the brain of Huntington's and Alzheimer's mouse models and found that overexpression of PYK2 in these 2 models improves synaptic properties and spine density deficits which is also accompanied by a rescue of spatial memory. Accordingly it was demonstrated that PYK2 may restore cognitive functions in neurodegenerative diseases. Thus the present invention relates to methods and pharmaceutical compositions for the treatment of neurodegenerative disease.