The invention relates to iRNA agents, which preferably include a monomer in which the ribose moiety has been replaced by a moiety other than ribose. The inclusion of such a monomer can allow for modulation of a property of the iRNA agent into which it is incorporated, e.g., by using the non-ribose moiety as a point to which a ligand or other entity, e.g., a lipophilic moiety. e.g., cholesterol, is is directly, or indirectly, tethered. The invention also relates to methods of making and using such modified iRNA agents.

The present invention aims to provide a new nucleic acid molecule for suppressing expression of the target gene, which (1) has a gene expression suppressing activity equivalent to or higher than that of siRNA, (2) shows no off-target effect of the sense strand, and (3) makes it possible to design a wider range of antisense strand sequences (extends the range of targetable sequences). Since the nucleic acid molecule of the following formula:

##STR00001##

wherein each symbol is as defined in the DESCRIPTION, has the superior properties of the above-mentioned (1) to (3), it is extremely useful as a novel gene expression inhibitor that replaces conventional siRNA.

The present invention provides cell-free systems comprising: (i) a transcription compartment; (ii) a barrier; and (iii) a translation compartment, methods for producing proteins and performing post-translational modifications thereon using such systems, and kits comprising such systems.

The present invention concerns methods and reagents useful in modulating gene expression in a variety of applications, including use in therapeutic, diagnostic, target validation, and genomic discovery applications. Specifically, the invention relates to synthetic chemically modified small nucleic acid molecules, such as short interfering nucleic acid (siNA), short interering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), and short hairpin NA (shRNA) molecules capable of mediating RNA interference (RNAi) against target nucleic acid sequences. The small nucleic acid molecules are useful in the treatment of any disease or condition that responds to modulation of gene expression or activity in a cell, tissue, or organism.

Provided herein are oligonucleotide agents comprising one or more therapeutic oligonucleotides such as siRNA and one or more targeting conjugate compounds. In certain embodiments, the conjugate compound comprises one or more N-Acetylgalactosamine as targeting group, branching group and linker group. By incorporating long carbon chains into the GalNAc clusters instead of using multiple amide groups to elongate the chain length, simplification of the synthesis by reducing the number of steps is achieved.

The invention relates to a new method for obtaining aptamers directed against protein targets comprising a histidine-containing surface domain, and aptamers obtaining by said method.

The present invention relates to antisense oligonucleotides that are capable of modulating expression of Tau in a target cell. The oligonucleotides hybridize to MAPT mRNA. The present invention further relates to conjugates of the oligonucleotide and pharmaceutical compositions and methods for treatment of Tauopathies, Alzheimzer's disease, fronto-temporal dementia (FTD), FTDP-17, progressive supranuclear palsy (PSP), chronic traumatic encephalopathy (CTE), corticobasal ganglionic degeneration (CBD), epilepsy, Dravet syndrome, depression, seizure disorders and movement disorders.

This disclosure describes methods and compositions for protein and peptide sequencing.

The invention relates to the field of oligonucleotide therapeutics, and in particular to the use of a cleavable, e.g. a phosphodiester region covalently attached to a conjugate, a targeting group or blocking group to enhance the properties of the oligonucleotides, for example to improve the therapeutic index.

The present invention discloses preparation and use of a nanoparticle-doped RNA hydrogel targeting to a triple negative breast cancer (TNBC). The RNA hydrogel is a pure RNA system formed in a rolling circle transcription manner. The transcription process generates a large number of GC bonds, which provides a large number of sites for the introduction of DOX. The large number of RNA copy structures generated by rolling circle replication is a polyanionic aggregate. Due to the strong electronegativity of the polyanionic aggregate, electropositive MnO.sub.2@Ce6 nanoparticles are introduced, such that the colloid cationic MnO.sub.2@Ce6 particles can be stabilized by the polyanionic hydrogel, and thus target into a breast cancer cell for synergistic treatment. It can be used for a drug slow release system, has good biocompatibility, and has broad prospects in the fields of growth inhibition effects on targeted MDA-MB-231 tumor cells, inhibition of cancer metastasis and recurrence, and the like.