The present disclosure provides oligomeric compounds (including oligomeric compounds that are antisense agents or portions thereof) comprising a modified oligonucleotide having at least one modified internucleoside linking group.

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, Alzheimer'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.

The present invention provides, among other things, methods for purifying mRNA based on normal flow filtration for therapeutic use.

Provided is a small RNA, a composition comprising the small RNA, a method for using same and use of same. The small RNA or composition can inhibit the ability of any one or more of pathways or genes listed in Table 3, or decrease or down regulate the expression level of IL-1 beta, IL-6, and/or TNF-alpha in vitro or in vivo, or treat or prevent IL-1 beta, IL-6, and/or TNF-alpha related diseases and/or increase cell viability in a subject.

The present invention relates to oligomeric compounds and conjugates thereof that target Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) PCSK9 mRNA in a cell, leading to reduced expression of PCSK9. Reduction of PCSK9 expression is beneficial for a range of medical disorders, such as hypercholesterolemia and related disorders.

It is a first object of the present invention to provide a method for preparing a Tile vector, being a vector, which comprises a selectable marker and a coding polynucleotide, wherein said coding polynucleotide is immediately preceded and followed by a type IIs recognition sequence, wherein said preceding and following recognition sequences are recognized by a same type IIs restriction enzyme, but have an opposite orientation. More particularly, the position and orientation of said preceding and following type IIs recognition sequences provides for the cleavage of said Tile vector by a corresponding type IIs restriction enzyme resulting in the release of said coding polynucleotide sequence having at its respective ends overhang sequences with a known orientation and length, while lacking said preceding and following type IIs recognition sequences. In a second object the present invention provides a method for using such Tile vectors obtained as previously described for joining two or more coding polynucleotides to form a product polynucleotide. Typically, said product polynucleotide is integrated in a vector.

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.

Disclosed herein are methods and compositions related to the use of the Argonaute-3 (AGO3) polypeptide in disease detection, prevention, and treatment. Specifically, disclosed herein are cleavage-inducing tiny RNAS (cityRNAs) which are capable of inducing AGO3 to slice nucleic acids. This powerful tool can be used in a variety of applications.

Provided herein, in some embodiments, are methods, compositions and kits for large-scale production of long single-stranded DNA in solution.

Disclosed are compositions, systems, kits, and methods for detecting an analyte or target molecule in a sample by regulated in vitro transcription. The compositions, systems, kits, and methods typically comprise and/or utilize one or more components selected from: (a) an RNA polymerase; (b) an allosteric transcription factor (ATT), wherein the ATT binds an analyte or target molecule as a ligand; (c) an engineered transcription template; and/or any combination thereof. The engineered transcription template typically comprises a promoter sequence for the RNA polymerase and an operator sequence for the ATT. The promoter sequence and operator sequence are operably linked to a sequence encoding an RNA, wherein the ATT modulates transcription of the encoded RNA when the ATT binds the analyte or target molecule as a ligand, wherein the transcribed RNA generates a detectable signal in conjunction with a reporter molecule.