Abstract: The present invention provides, inter alia, methods for treating, preventing, or ameliorating the effects of a lymphoid malignancy, such as those associated with a mutated phosphatase and tensin homolog (PTEN) gene, or T-cell acute lymphoblastic leukemia (T-ALL). These methods include administering to a subject an effective amount of a phosphoinositide 3-kinase-delta (PI3K?) inhibitor and a phosphoinositide 3-kinase-gamma (PI3K?) inhibitor. The present invention also provides pharmaceutical compositions for treating the effects of a lymphoid malignancy. This invention further provides a method for identifying a subject who may benefit from co-treatment with a PI3K? inhibitor and a PI3K? inhibitor. This method includes determining from a sample of the subject whether the subject has a mutated PTEN gene. Additionally, this invention provides methods for identifying a compound that has both PI3K? and PI3K? inhibitory activity.

Abstract: Compositions and methods for editing, e.g., introducing double-stranded breaks, within the TTR gene are provided. Compositions and methods for treating subjects having amyloidosis associated with transthyretin (ATTR), are provided.

Abstract: Embodiments of the disclosure include methods and compositions related to treating or reducing the severity or delaying the onset of one or more cardiac conditions in a mammal. In particular embodiments, the compositions concern Park2 and its use for a cardiac medical condition. In specific cases, effective amounts of Park2 polynucleotide(s) and/or Park2 polypeptide(s) are provided to an individual in need thereof, including for heart failure, for example. The administration may be locally to the heart, for example.

Abstract: Provided are compositions and methods for altering gene expression in cells. The compositions and methods may utilize a nucleic acid sequence that has a genetically modified trans-activating crRNA (tracrRNA) sequence, where at least one uracil nucleotide of the tracrRNA sequence is replaced with a nucleotide other than uracil, and/or a nucleic acid sequence that has a guide RNA (gRNA) sequence wherein one or more cytosine nucleotides and/or one or more uracil nucleotides of said gRNA sequence are modified nucleotides. Also provided are methods of treating a disorder in a subject in need of the treatment. The method may involve administering to the subject the nucleic acid or a vector thereof in combination with an RNA-guided DNA endonuclease enzyme.

Abstract: Retrotransposons, operating though human-specific neurological pathways, can contribute to environment, lifestyle, and/or age-related neurodegeneration by disrupting functional mitochondrial populations within neurons. The mitochondrial disruption can occur through a number of retrotransposon-induced mechanisms that can influence the efficient and accurate transcription and/or translation of mitochondrial genes encoded in the nuclear genome, operating primarily through epigenetic processes. Alu element-related conformational changes (both subtle and major) of the outer and inner mitochondrial membrane pores can restrict or prevent the normal translocation of proteins (i.e., TOMM and TIMM complexes), ultimately contributing to mitochondrial stress, mitophagy, inflammation, and neuron and glial cell death.

Abstract: Provided herein are methods for using RNAi molecules targeting a proteasome beta 5 (PSMB5) gene for controlling Coleopteran insects, methods for producing RNAi molecules targeting PSMB5, and compositions comprising RNAi molecules targeting PSMB5.

Abstract: This invention provides compounds, compositions and methods for modulating the expression of target genes using RNA interference. RNAi structures and molecules of this invention can be used for modulating or silencing the expression of genes, with high levels of RNAi activity and reduced off target actions. Advantageous structures include siRNAs targeted to any gene having one or more 2?-deoxy nucleotides located in the seed region. The RNA interference molecules can be used in methods for preventing or treating diseases.

Abstract: The present invention relates to RNAi agents, e.g., dsRNA agents, targeting the ketohexokinase (KHK) gene. The invention also relates to methods of using such RNAi agents to inhibit expression of a KHK gene and to methods of treating or preventing a KHK-associated disorder in a subject.

Abstract: Described are RNAi agents, compositions that include RNAi agents, and methods for inhibition of a Superoxide Dismutase 1 (SOD1) gene. The SOD1 RNAi agents and RNAi agent conjugates disclosed herein inhibit the expression of an SOD1 gene. Pharmaceutical compositions that include one or more SOD1 RNAi agents, optionally with one or more additional therapeutics, are also described. Delivery of the described SOD1 RNAi agents to central nervous system (CNS) tissue, in vivo, provides for inhibition of SOD1 gene expression and a reduction in SOD1 activity, which can provide a therapeutic benefit to subjects, including human subjects, for the treatment of various diseases including amyotrophic lateral sclerosis (ALS.).

Abstract: A method for in vitro transcription of a DNA template into RNA includes providing a mixture containing a buffer substance, ribonucleoside triphosphates (NTPs), one or more magnesium salts in a concentration of from about 2 mM to about 60 mM, the DNA template, and a recombinant RNA polymerase, and incubating the reaction mixture at from about 25° C. to about 40° C. for from about 1 hour to about 12 hours thereby producing the RNA. A method for in vitro transcription includes providing a DNA template and a cap analogue that binds to ?1 and/or +1 nucleotides of promoter for in vitro transcription, thus producing more full length mRNAs, allowing for more flexibility on the choice of first mRNA base, and providing +2 position open for custom sequence.

Abstract: Disclosed herein include methods and compositions for modulating sodium appetite and/or intake. In some embodiments, the sodium appetite of a subject is reduced. Also disclosed include methods for identifying modulators for sodium appetite and/or intake.

Abstract: Provided herein are double-stranded nucleic acid inhibitor molecules having a sense strand with a stem loop structure and an antisense strand, where the stem portion of the stem loop structure contains one or more Tm-increasing nucleotides. Also provided are methods and compositions for reducing target gene expression and methods and compositions for treating a disease of interest.

Abstract: The invention relates to iRNA, e.g., double-stranded ribonucleic acid (dsRNA), compositions targeting the complement component C5 gene, and methods of using such iRNA, e.g., dsRNA, compositions to inhibit expression of C5 and to treat subjects having a complement component C5-associated disease, e.g., paroxysmal nocturnal hemoglobinuria.

Abstract: The present invention relates to oligonucleotides that are capable of inducing expression of ubiquitin-protein ligase E3A (UBE3A) from the paternal allele in animal or human neurons. The oligonucleotides target the suppressor of the UBE3A paternal allele by hybridization to SNHG14 long non-coding RNA downstream of SNORD109B. The present invention further relates to pharmaceutical compositions and methods for treatment of Angelman syndrome.

Abstract: The present invention relates to a composition for gene manipulation for treating or improving a retinal dysfunction disease or a method using the same. More particularly, the present invention relates to a composition for gene manipulation including a guide nucleic acid capable of targeting a retinal function-forming gene and a method of treating or improving a disease caused by retinal dysfunction by artificially manipulating and/or correcting a retinal function-forming gene using the same.

Abstract: Disclosed herein are antisense compounds and methods for decreasing Ataxin 2 mRNA and protein expression. Such methods, compounds, and compositions are useful to treat, prevent, or ameliorate Ataxin 2 associated diseases, disorders, and conditions. Such Ataxin 2 associated diseases include spinocerebellar ataxia type 2 (SCA2), amyotropic sclerosis (ALS), and parkinsonism.

Abstract: An adipocyte-targeting DNA nanodrug, and preparation and uses thereof. The drug is composed of an adipocyte-targeting DNA microstructure and tannic acid (TA) in a weight ratio of 1:25-30. Among them, the small molecular antioxidant TA is loaded into the DNA microstructure. The DNA microstructure incorporated with an adipocyte-targeting aptamer sequence can specifically recognize and bind with adipocytes. TA and DNA microstructure can interact with each other through multiple hydrogen bonds to form the adipocyte-targeting, safe and efficient DNA nanodrug.

Abstract: Provided herein are immunotherapy compositions for treating a subject with a glioblastoma, comprising a peptide formulation derived from at least one cancer or stemness factor, nanoparticles containing peptides derived from at least one cancer or stemness factor, dendritic cells containing peptides derived from at least one cancer or stemness factors, RNA coding at least one cancer or stemness factor, nanoparticles containing RNA coding at least one cancer or stemness factor, dendritic cells containing RNA coding at least one cancer factor or stemness factor, or an inhibitor of at least one cancer or stemness factor. Also provided are methods of inhibiting a glioblastoma stem-like cell (GSC), methods of treating a subject for glioblastoma, and methods of reprogramming an astrocyte to a glioblastoma stem-like cell (GSC) using such immunotherapy compositions.

Abstract: The present disclosure relates to compositions and methods for modulating gene expression and in particular to compositions and methods for increasing expression of Klotho. For example, the present disclosure provides methods for increasing expression of a Klotho gene in a human cell comprising introducing into the cell a CRISPR enzyme and a guide RNA comprising a guide sequence that is substantially complementary to a target sequence within or near the Klotho gene, wherein the guide RNA or the CRISPR enzyme associates with a transcriptional activation domain.

Abstract: Provided herein are synthetic nucleic acid molecules known as loop-mediated riboregulators that have single-nucleotide polymorphism (SNP) sensitivity and ultralow OFF state signal levels. Loop-mediated riboregulators can activate or repress gene expression in response to trigger RNAs bearing completely arbitrary sequences. Also provided herein are methods of using such synthetic nucleic acid molecules for detecting the presence or absence of a particular target RNA in, for example, a biological sample.