The present invention relates to the use of a DBait molecules by systemic routes without any combination with an endosomolytic agent.

The disclosure relates to double stranded ribonucleic acid (dsRNAi) agents and compositions targeting a human chromosome 9 open reading frame 72 (C9orf72) gene, as well as methods of inhibiting expression of a C9orf72 gene and methods of treating subjects having a C9orf72-associated disease or disorder, e.g., C9orf72 amyotrophic lateral sclerosis, frontotemporal dementia or Huntington-Like Syndrome Due To C9orf72 Expansions, using such dsRNAi agents and compositions.

The present invention is related to a ribonucleic acid comprising a double stranded structure whereby the double-stranded structure comprises a first strand and a second strand, whereby the first strand comprises a first stretch of contiguous nucleotides and whereby said first stretch is at least partially complementary to a target nucleic acid, and the second strand comprises a second stretch of contiguous nucleotides whereby said second stretch is at least partially identical to a target nucleic acid, and whereby the double stranded structure is blunt ended.

Optimized inhibitory nucleic acids are provided. The nucleic acids have sequences which include an optimal inhibitory motif, such as a GGG. Related methods are also described.

The present invention is related to a ribonucleic acid comprising a double stranded structure whereby the double-stranded structure comprises a first strand and a second strand, whereby the first strand comprises a first stretch of contiguous nucleotides and whereby said first stretch is at least partially complementary to a target nucleic acid, and the second strand comprises a second stretch of contiguous nucleotides whereby said second stretch is at least partially identical to a target nucleic acid, and whereby the double stranded structure is blunt ended.

A method of altering the functional state of any mRNA enabling its selective and specific recognition and subsequent selective manipulation and a universal principle for increasing the specificity and selectivity of molecular target recognition at the level of nucleic acids. The principle of the specific and selective recognition of nucleic acids is based on simultaneous recognition of two or more sequences of the target nucleic acid, whereas these have to be spaced from each other by a certain defined distance. Such method of nucleic acid recognition through specific recognition of well-defined sequences of the nucleic acid that are spaced from each other by a defined distance, minimizes the probability of stable binding of the interfering construct to inadvertent nucleic acids, thereby dramatically increasing the selectivity of recognition of the targeted nucleic acid. Specific recognition of defined sequences of a nucleic acid localized at a certain defined distance from each other is achieved by simultaneous complementary interference of short sequence-specific oligonucleotides being mutually interconnected by size-specific polymeric linking moiety.

Provided herein are aptamers capable of inhibiting the activity of Von Willebrand Factor (VWF). Pharmaceutical compositions comprising these aptamers are also provided. Methods of preventing blood clot formation in a subject by administering the aptamers are provided and methods of treating a blood clot by administering a VWF-targeting agent are also provided.

In one embodiment, the object of the present invention is to provide a nephrotoxicity reducing agent for a pharmaceutical composition comprising an antisense oligomer, and a method for reducing nephrotoxicity of the pharmaceutical composition. In one embodiment, the present invention relates to a nephrotoxicity reducing agent for a pharmaceutical composition comprising an antisense oligomer, wherein the nephrotoxicity reducing agent comprises a non-glucose sugar and is used in an amount such that the concentration of the sugar in the pharmaceutical composition is 1 mg/ml to 400 mg/mL.

In one embodiment, the object of the present invention is to provide a nephrotoxicity reducing agent for a pharmaceutical composition comprising an antisense oligomer, and a method for reducing nephrotoxicity of the pharmaceutical composition. In one embodiment, the present invention relates to a nephrotoxicity reducing agent for a pharmaceutical composition comprising an antisense oligomer, wherein the nephrotoxicity reducing agent comprises a non-glucose sugar and is used in an amount such that the concentration of the sugar in the pharmaceutical composition is 1 mg/ml to 400 mg/mL.

This disclosure relates to modified guide RNAs having improved in vitro and in vivo activity in gene editing methods. This disclosure also relates to N. meningitidis Cas9 (NmeCas9) gene editing systems with modified guide RNAs.