The present disclosure features useful compositions and methods to treat disorders for which deamination of an adenosine in an mRNA produces a therapeutic result, e.g., in a subject in need thereof.

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′.

The present disclosure describes compositions of matter comprising a ribonucleoprotein complex comprising a nucleic acid-guided nuclease and a guide RNA, and further comprising and a blocking nucleic acid molecule represented by Formula I, wherein Formula I in the 5′-to-3′ direction comprises: A-(B-L).sub.J-C-M-T-D; wherein A is 0-15 nucleotides in length; B is 4-12 nucleotides in length; L is 3-25 nucleotides in length; J is an integer between 1 and 10; C is 4-15 nucleotides in length; M is 1-25 nucleotides in length or is absent, wherein if M is absent then A-(B-L).sub.J-C and T-D are separate nucleic acid strands; T is 17-135 nucleotides in length and comprises at least 50% sequence complementarity to B and C; D is 0-10 nucleotides in length and comprises at least 50% sequence complementarity to A; and wherein the blocking nucleic acid molecule comprises a sequence complementary to a gRNA.

Disclosed herein are conditional siRNAs activatable by CBFβ-MYH11 oncogenic gene and use thereof for treating conditions such as acute myeloid leukemia (AML). The conditional siRNAs target MCL-1 or HDAC8.

Provided herein are Factor V/Factor Va-targeting aptamer compositions and antidote compositions targeting such aptamer compositions. Methods for preventing blood clots using such compositions are also provided.

The present invention relates to guide RNAs having chemical modifications and their use in CRISPR-Cas systems. The chemically modified guide RNAs have enhanced specificity for target polynucleotide sequences. The present invention also relates to methods of using chemically modified guide RNAs for cleaving or nicking polynucleotides, and for high specificity genome editing.

The present disclosure describes a CRISPR nuclease cascade assay that can detect one or more target nucleic acids of interest of interest at attamolar (aM) (or lower) limits in about 10 minutes or less without the need for amplifying the target nucleic acids of interest. The CRISPR cascade assays utilize signal amplification mechanisms comprising various components including CRISPR nucleases, guide RNAs (gRNAs), blocked nucleic acid molecules, blocked primer molecules, and reporter moieties.

Described are improved disulfide-containing alkyne linking agents having have branched disulfides. The improved linking agents exhibit improved stability. The linking agents are useful for attachment of oligonucleotides to targeting groups or delivery agents.

Provided are antisense morpholino oligomers targeted against bacterial virulence factors such as genes that contribute to antibiotic resistance or biofilm formation, or genes associated with fatty acid biosynthesis, and related compositions and methods of using the oligomers and compositions, for instance, in the treatment of an infected mammalian subject.

The present invention refers to a modified D-amino acid oxidase (DAAO). In particular, the modified DAAO of the present invention has the activity of catalyzing the oxidation of D-glufosinate into PPO. Further, the modified DAAO of the present invention has increased activity of catalyzing the oxidation of D-glufosinate into PPO and/or increased stability as compared to SEQ ID NO: 4. The present invention also refers to the polynucleotide encoding the modified DAAO of the present invention, the vector and host cell expressing the modified DAAO of the present invention, and the method of producing L-glufosinate with the modified DAAO and host cell of the present invention.