The present invention refers to a method for the production of a catalytically active DNA molecule resulting in a significantly decreased amount of impurities in the catalytically active DNA molecule, to a catalytically active DNA molecule obtainable by such method and a pharmaceutical composition comprising such catalytically active DNA molecule as well as their use in a method for the prevention and/or treatment of a GATA-3-driven disease.

The present invention relates to a compound of formula (II) or (IIb) Wherein X, Y, R.sup.x, R.sup.y, R.sup.5 and Nu are as defined in the description and in the claims. The compound of formula (II) can be used in the manufacture of oligonucleotides. ##STR00001##

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.

Disclosed herein are compounds including a nucleic acid (A), their preparation, and their use.

Chemical syntheses of guide molecules are disclosed, along with compositions and methods relating thereto.

Disclosed herein include guide RNA (gRNA), such as single gRNA (sgRNA), and compositions thereof, comprising 2′-O-methyldithiomethyl modified sugar moieties which can be reduced to 2′-O-methanethiol groups in the reducing environment of cells and then converted (e.g., spontaneously converted) to 2′-OH. The resultant gRNA can bind to and direct the activity of an RNA-guided endonuclease (e.g., Cas9).

The present disclosure relates to multimeric oligonucleotides comprising subunits, each of the subunits independently comprises a single-stranded or double-stranded oligonucleotide. Each of the subunits is joined to another subunit by a covalent linker, and at least one subunit comprises at least one partial single-stranded oligonucleotide. The present disclosure also relates to methods of synthesizing the multimeric oligonucleotides and the methods of using the multimeric oligonucleotides disclosed herein.

Provided herein are novel synthetic routes to amines through an oxime intermediate, e.g., 3′-N nucleosides and novel and intermediate compounds produced during these synthetic procedures.

The invention provides engineered RNA precursors that when expressed in a cell are processed by the cell to produce targeted small interfering RNAs (siRNAs) that selectively silence targeted genes (by cleaving specific mRNAs) using the cell's own RNA interference (RNAi) pathway. By introducing nucleic acid molecules that encode these engineered RNA precursors into cells in vivo with appropriate regulatory sequences, expression of the engineered RNA precursors can be selectively controlled both temporally and spatially, i.e., at particular times and/or in particular tissues, organs, or cells.

A multi-conjugate comprising two or more covalently linked biological subunits, wherein at least two of the subunits are terminally located targeting ligands. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a therapeutic agent that is the multi-conjugate is also disclosed. The multi-conjugate may be administered to a subject for providing treatment or prophylaxis against a disease or other medical condition.