A method of modifying a gene encoding or processed into a non-coding RNA molecule having no RNA silencing activity in a plant cell is disclosed. The method comprising introducing into the plant cell a DNA editing agent conferring a silencing specificity of the non-coding RNA molecule towards a target RNA of interest. A method of modifying a gene encoding or processed into a RNA silencing molecule in a plant cell is also disclosed. The method comprising introducing into the plant cell a DNA editing agent which redirects the silencing specificity of the non-coding RNA molecule towards a target RNA of interest. Plant cells, plant seeds, plants, and methods of generating plants are also disclosed.

The present invention relates to large scale manufacture of nanoscale microsheets for use in applications such as wound healing or modification of a biological or medical surface.

The present invention relates to compositions and methods for treating cancer, particularly to agents that inhibit the expression and/or activity of the protein second mitochondria-derived activator of caspase/direct inhibitor of apoptosis-binding protein with low pI (SMAC/Diablo). The inhibiting agents include RNA interference molecules silencing the expression of SMAC/Diablo and peptides modulating its interactions within the cell nucleus and mitochondria. The methods and agents of the present invention are useful in treating cancers associated with overexpression of SMAC/Diablo.

Tissue for use as a transplant, which tissue is allogeneic or xenogeneic and respectively the tissue may express an MHC I molecule that is immunologically incompatible to the transplant recipient and/or may express an MHC II molecule immunologically incompatible to the transplant recipient. The tissue suitable for use as a transplant and the method for its production include a genetic alteration of the tissue that provides for immunologic compatibility of the tissue with a transplant recipient. In the tissue for use as a transplant, which tissue expresses allogeneic or xenogeneic MHC I and/or allogeneic or xenogeneic MHC II molecules, the expression of the allogeneic or xenogeneic MHC I is downregulated by at least 50% to up to 90%, preferably the expression of the allogeneic or xenogeneic MHC I is downregulated by at least 60%.

Provided is a nucleoside derivative represented by the following formula (1):

##STR00001##

or a salt thereof, wherein R.sup.1 represents an alkoxy group, a hydrogen atom or a halogen atom; R.sup.2 and R.sup.4, which may be the same as or different from each other, each represents a hydrogen atom, a protective group for a hydroxyl group, a phosphate group, a protected phosphate group, or —P(═O).sub.nR.sup.5R.sup.6 in which n represents 0 or 1, R.sup.5 and R.sup.6, which may be the same as or different from each other, each represents a hydrogen atom, a hydroxyl group, a protected hydroxyl group, a mercapto group, a protected mercapto group, an alkoxy group, a cyanoalkoxy group, an amino group, or a substituted amino group, provided that when n is 1, both R.sup.5 and R.sup.6 cannot be the hydrogen atom at the same time; R.sup.3 represents —(CH.sub.2).sub.mNHR.sup.7 in which m represents an integer of 1 to 6, R.sup.7 represents a hydrogen atom, an alkyl group, an alkenyl group or a protective group for an amino group; and B represents a purin-9-yl group, a 2-oxo-pyrimidin-1-yl group, a substituted purin-9-yl group, or a substituted 2-oxo-pyrimidin-1-yl group.

Methods and compositions for modulating transforming growth factor-beta (TGFβ) 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 TGFβ biological activity in the vertebrate subject.

The present disclosure relates to gene therapy targeting GluK2 subunit that can be used to inhibit epileptiform discharges. Short interfering RNA sequences against the human Grik2 gene sequence are described which are efficient in decreasing the expression of GluK2-containing KARs in neurons engineered to express the equivalent shRNA or miRNA. Using a tissue culture model of TLE, the examples remarkably demonstrate that viral expression of shRNA or miRNA inhibits the frequency of epileptiform discharges. Therefore, RNA therapeutics aimed at decreasing the expression of GluK2-containing KARs in neurons can remarkably prevent spontaneous epileptiform discharges in TLE. In particular, the present disclosure relates to a recombinant antisense oligonucleotide that targets a Grik2 mRNA. The present disclosure also relates to a method for treating epilepsy in a subject in need thereof, wherein the method comprises: administering an effective amount of a vector comprising an oligonucleotide encoding an inhibitory RNA that binds (e.g., hybridizes) specifically to Grik2 mRNA and inhibits expression of Grik2 in the subject.

Aspects of the disclosure relate to complexes comprising a muscle-targeting agent covalently linked to a molecular payload. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload inhibits expression or activity of DUX4. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide or RNAi oligonucleotide.

This invention provides compounds, compositions and methods for modulating the expression of human GST-π using RNA interference. The RNA interference molecules can be used in methods for preventing or treating diseases such as malignant tumor. Provided are a range of siRNA structures, having one or more of nucleotides being modified or chemically-modified. Advantageous structures include siRNAs with 2′-deoxy nucleotides located in the seed region, as well as other nucleotide modifications.

Described are compositions and methods for inhibition of Hepatitis B virus gene expression. RNA interference (RNAi) agents for inhibiting the expression of Hepatitis B virus gene are described. The HBV RNAi agents disclosed herein may be targeted to cells, such as hepatocytes, for example, by using conjugated targeting ligands. Pharmaceutical compositions comprising one or more HBV RNAi agents optionally with one or more additional therapeutics are also described. Delivery of the described HBV RNAi agents to infected liver in vivo provides for inhibition of HBV gene expression and treatment of diseases and conditions associated with HBV infection.