The invention relates to RNAi agents, e.g., double-stranded RNAi agents, targeting the Serpina1 gene, and methods of using such RNAi agents to inhibit expression of Serpina1 and methods of treating subjects having a Serpina1 associated disease, such as a liver disorder.

A method produces a hairpin single-stranded RNA molecule capable of inhibiting expression of a target gene, including the step of reacting a first single-stranded oligo-RNA molecule represented by formula (I) with a second single-stranded oligo-RNA molecule represented by formula (II) in a mixed solvent including a buffer solution and a hydrophilic organic solvent in the presence of a dehydration condensation agent: 5′-Xc-Lx.sup.1 (I) and Lx.sup.2-X—Y-Ly-Yc-3′ (II), wherein the dehydration condensation agent is selected from the group consisting of a triazine-based dehydration condensation agent, a uronium-based dehydration condensation agent including an N-hydroxy nitrogen-containing aromatic ring structure, a carbodiimide-based dehydration condensation agent, a 2-halopyridinium-based dehydration condensation agent, and a formamidinium-based dehydration condensation agent.

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

An encrypted rolling code, a plurality of differing data bit order patterns, and a plurality of differing data inversion patterns are provided. One then selects a particular one of each of these patterns and uses those selected patterns as transmission characteristics when transmitting at least part of the encrypted rolling code.

Chemical syntheses of guide molecules are disclosed, along with compositions and methods relating thereto. A cost-effective and straightforward chemical synthesis of high-purity unimolecular guide molecules with minimal n−1 and/or n+1 species, truncation species, and other contaminants by providing, among other things, methods for synthesizing unimolecular guide molecules that involve cross-linking two or more pre-annealed guide fragments.

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 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.

Disclosed herein are novel synthetic bacteriophages and bacteriophage compositions, methods of production thereof, and therapeutic uses thereof.

Among other things, the present disclosure provides designed DMD oligonucleotides, compositions, and methods of use GC thereof. In some embodiments, the present disclosure provides technologies useful for repairing mutant DMD transcripts by skipping exon 51 or exon 53, so that the transcript can be translated into an internally truncated but at least partially functional Dystrophin protein variant. In some embodiments, the present disclosure provides technologies useful for modulating DMD transcript splicing. In some embodiments, provided technologies can alter splicing of a dystrophin (DMD) DMD transcript. In some embodiments, the present disclosure provides methods for treating diseases, such as muscular dystrophy, including but not limited to Duchenne muscular dystrophy, Becker's muscular dystrophy, etc.

The invention provides a single-stranded nucleic acid molecule and a production method thereof. The single-stranded nucleic acid molecule is represented by formula (I):

##STR00001##

wherein each symbol is as described in the description.