Abstract: Provided herein are methods and compositions for treating a subject in need thereof, such as a subject with deficient SYNGAP1 protein or SCN1A protein expression or a subject having AD mental retardation 5 or Dravet syndrome.

Abstract: The present disclosure provides compounds comprising oligonucleotides complementary to a portion of the IKBKAP gene. Certain such compounds are useful for hybridizing to a portion of the IKBKAP gene, including but not limited to a portion of the IKBKAP gene in a cell. In certain embodiments, such hybridization results in modulation of splicing of the IKBKAP gene. In certain embodiments, the IKBKAP gene includes a mutation that results in defective splicing and a truncated IKAP protein. In certain embodiments, hybridization of oligonucleotides complementary to a portion of the IKBKAP gene results in a decrease in the amount of defective splicing and truncated IKAP protein. In certain embodiments, hybridization of oligonucleotides complementary to a portion of the IKBKAP gene results in an increase in the amount of normal splicing and functional, full-length IKAP protein. In certain embodiments, oligonucleotides are used to treat Familial Dysautonomia.

Abstract: Provided herein are methods, compounds, and compositions for reducing expression of a MaTAR in an animal. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate breast cancer in an individual in need.

Abstract: Provided herein are methods, compounds, and compositions for reducing expression of Inc05 in a cell or individual. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate a cancer in an individual.

Abstract: A method for determining the number of nucleic acid molecules (NAMs) in a group of NAMs, comprising i) obtaining an amplified and mutagenized group of NAMs that was produced by a. subjecting the group of NAMs to a chemical mutagenesis which mutates only select nucleic acid bases in the group of NAMs at a rate of 10% to 90% thus forming a group of mutagenized NAMs (mNAMs), and b. amplifying the group of mNAMs; ii) obtaining sequences of the mNAMs in the group of amplified mNAMs; and iii) counting the number of different sequences obtained in step (ii) to determine the number of unique mNAMs in the group of mNAMS, thereby determining the number of NAMs in the group of NAMs.

Abstract: A method is disclosed for altering the redox equilibrium of a transmembrane receptor-like protein tyrosine phosphatase (RPTP), particularly a type IIa RPTP, by chemically modulating the activity through contact of such an enzyme with a diaryl boron compound that preferentially reacts with an RPTP in an oxidized state (CyS-OH). This redox modulation is most readily observed and put to use by assaying the inhibition of the phosphatase activity of the RPTP. Such an assay can be carried out on an enzyme in vitro or by contacting the enzyme in a living organism (in vivo). A useful diaryl boron compound corresponds in structure to Formula I in which Ar-1, Ar-2, R1, R2, R3 and R4 are defined within. A pharmaceutical composition containing a useful diaryl boron compound is also disclosed, as are particularly preferred diaryl boron compounds.

Abstract: A method for obtaining from genomic material genomic copy number information unaffected by amplification distortion, comprising obtaining segments of the genomic material, tagging the segments with substantially unique tags to generate tagged nucleic acid molecules, such that each tagged nucleic acid molecule comprises one segment of the genomic material and a tag, subjecting the tagged nucleic acid molecules to amplification by polymerase chain reaction (PCR), generating tag associated sequence reads by sequencing the product of the PCR reaction, assigning each tagged nucleic acid molecule to a location on a genome associated with the genomic material by mapping the subsequence of each tag associated sequence read corresponding to a segment of the genomic material to a location on the genome, and counting the number of tagged nucleic acid molecules having a different tag that have been assigned to the same location on the genome, thereby obtaining genomic copy number information unaffected by amplification d

Abstract: Provided is a method of forming a copper-containing complex, including contacting a sample containing copper with a compound of Formula I: wherein R is —OH or —O—CH3. Also provided is a method of inhibiting enzymatic activity of a kinase in a sample, including contacting the sample with a compound of Formula I. Further provided is a method of administering to a subject a pharmaceutical composition including a compound of Formula I optionally complexed with copper. Also provided is a pharmaceutical composition including copper complexed with a compound of Formula I.

Abstract: Disclosed herein are compounds, compositions and methods for modulating splicing of SMN2 mRNA in a subject. Also provided are uses of disclosed compounds and compositions in the manufacture of a medicament for treatment of diseases and disorders, including spinal muscular atrophy.

Abstract: Aspects of the disclosure relate to plants, such as Solanaceae plants containing one or more branching events of a mutant Solyc04g005320 gene (or a homolog thereof), a mutant Solycl2g038510 gene (or a homolog thereof), and a mutant Solyc03gl 14840 gene (or a homolog thereof), as well as methods of producing such plants. In some aspects, such plants have one or more improved traits, such as modified inflorescence architecture, modified flower number, modified fruit number, higher yield, higher quality products, and higher fruit productivity.

Abstract: Described herein is a florigen pathway toolkit that comprises mutations in genes in the florigen pathway in Solanaceae, such as mutations in genes in the florigen pathway in tomatoes, that are useful to quantitatively modulate or adjust the balance of opposing flowering signals to customize and improve shoot architecture and flowering (flowering time) for tomato breeding, particularly for fresh market tomato breeding.

Abstract: The present disclosure relates to compositions and methods for inhibiting nonsense-mediated mRNA decay in a gene-specific manner, for example in the treatment of diseases or disorders caused by nonsense mutations.

Abstract: The present invention, SMASH (Short Multiply Aggregated Sequence Homologies), is a technique designed to pack multiple independent mappings into every read. Specifically, the invention relates to a composition comprising a first mixture of different chimeric genomic nucleic acid fragments, wherein each different fragment in the mixture comprises randomly ligated DNA segments, wherein each DNA segment in the fragment is a nucleic acid molecule at least 27 base pairs in length resulting from random fragmentation of a single genome. The invention also relates to methods for generating said composition and use of said composition to obtain genomic information, for example, copy number variation.

Abstract: Provided herein are methods and compositions for increasing production of a target protein or functional RNA by a cell.

Abstract: Provided herein are compositions and methods for generating alleles of genes of interest in plants. In some aspects, libraries of plants or seeds are provided that comprise an expression construct comprising a RNA-guided endonuclease (e.g., a Cas9 endonuclease) and multiple different guide RNAs that target regions of the gene of interest, such as regulatory regions.

Abstract: Disclosed herein are compounds, compositions and methods for modulating splicing of SMN2 mRNA in a cell, tissue or animal. Also provided are uses of disclosed compounds and compositions in the manufacture of a medicament for treatment of diseases and disorders, including spinal muscular atrophy.

Abstract: Methods and compositions for modulating shoot apical meristem size are provided. Methods are provided for modulating the expression of fea3 sequence in a host plant or plant cell to modulate agronomic characteristics such as altered size and number of organs, including plant seeds.

Abstract: The present disclosure relates to compositions and methods for inhibiting nonsense-mediated mRNA decay in a gene-specific manner, for example in the treatment of diseases or disorders caused by nonsense mutations.

Abstract: Methods and compositions for modulating shoot apical meristem size are provided. Methods are provided for modulating the expression of fea3 sequence in a host plant or plant cell to modulate agronomic characteristics such as altered size and number of organs, including plant seeds.

Abstract: Provided is an improved design of shRNA based on structural mimics of miR-451 precursors. These miR-451 shRNA mimics are channeled through a novel small RNA biogenesis pathway, require AGO2 catalysis and are processed by Drosha but are independent of DICER processing. This miRNA pathway feeds active elements only into Ago2 because of its unique catalytic activity. These data demonstrate that this newly identified small RNA biogenesis pathway can be exploited in vivo to produce active molecules.