Disclosed herein are conditional siRNAs activatable by pro-hypertrophic RNA sequences and use thereof for treating conditions such as cardiac hypertrophy. The conditional siRNAs target calcineurin or HDAC2.

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).

Disclosed herein are double-stranded polyribonucleotides comprising a sense strand with 24 to 30 nucleotides in length and an antisense strand with 24 to 30 nucleotides in length, wherein the sense strand and the antisense strand form a fully complementary region of at least 24 base pairs with a blunt end at the 5′-end of the sense strand and the 3′-end of the antisense strand; and wherein the first 24 ribonucleotides at 5′-end of the sense strand further have at least one 2′-flourine modification at a ribonucleotide at a position selected from the group consisting of position number 2, 4, 6, 9, 10, 16, 21, 22, and 24, and no 2′-flourine modification at a ribonucleotide at a position selected from the group consisting of position number 1, 3, 8, and 14, and/or wherein the last 24 ribonucleotides at 3′-end of the antisense strand further have at least one 2′-flourine modification at a ribonucleotide at a position selected from the group consisting of position number 5, and 13, and no 2′-flourine modification at a ribonucleotide at a position selected from the group consisting of position 18 and 23; wherein all positions are counted from 5′ to 3′.

Provided herein are self-delivering oligonucleotides that are characterized by efficient RISC entry, minimum immune response and off-target effects, efficient cellular uptake without formulation, and efficient and specific tissue distribution.

The present invention relates, in general to agents that modulate the pharmacological activity of conjugated siRNAs.

The present disclosure provides DNA-guided CRISPR systems; polynucleotides comprising DNA, RNA and mixtures thereof for use with CRISPR systems; and methods of use involving such polynucleotides and DNA-guided CRISPR systems.

Described herein are compositions for targeting and editing genomes. Also described herein are methods for targeting and editing genomes utilizing the compositions in the instant disclosure.

The present invention provides an antisense nucleic acid medicine that can modulate expression of a target transcriptional product in an ischemic site of a subject. The present invention also provides a composition for modulating expression of a target transcriptional product in an ischemic site of a subject, having a nucleic acid complex formed by annealing together a first nucleic acid strand having an antisense oligonucleotide region with respect to the target transcriptional product, and a lipid-conjugated second nucleic acid strand having a complementary region that is complementary to at least part of the first nucleic acid strand.

The invention relates to a method of identifying stereodefined phosphorothioate oligonucleotide variants with reduced toxicity by creating and screening libraries of stereodefined chiral phosphorothioate variants for compounds with reduced toxicity, either in vitro or in vivo.

The present invention aims to provide an antisense oligonucleic acid with reduced hepatotoxicity. The antisense oligonucleic acid according to the present invention is characterized in that it has a base length of not less than 7 nt and not more than 30 nt, wherein nucleic acid residues of not less than 1 nt and not more than 5 nt respectively from the both terminals are 2′,4′-bridged nucleic acids, 2′,4′-non-bridged nucleic acid residue(s) is(are) present between the above-mentioned both terminals, and one or more bases in the nucleic acid residue(s) of the above-mentioned 2′,4′-non-bridged nucleic acid residue(s) is/are modified.