Provided herein are compositions of engineered guide RNAs relating to providing or engineering a structural target to attract adenosine deaminase acting on RNA (ADAR) editing to a desired site and methods of use thereof. Further provided herein are compositions and methods relating to recombinant adenosine deaminase acting on RNA (ADAR) split guide RNAs (adar-sgRNA). In certain embodiments, the adar-sgRNA composition comprises two guides-one guide with an ADAR recruiting domain and a second guide with a 5′ and/or 3′ RNA targeting domain for forming a trimolecular complex at a mismatch site that serves to recruit ADAR. Binding of the two adar-split gRNAs to the target RNA forms a trimolecular complex which recruits ADAR enzymes to deaminate one or more mismatched adenosine residues in the adar-split gRNA RNA targeting domain: target RNA duplex. In certain embodiments, such compositions and methods will be useful for modifying a coding sequence of a desired protein.

A method of reducing the level of a transcription product in a cell comprising contacting with the cell a composition comprising a double-stranded nucleic acid complex comprising a first nucleic acid strand annealed to a second nucleic acid strand, wherein: (i) the first nucleic acid strand hybridizes to the transcription product and comprises (a) a region consisting of at least 4 consecutive nucleotides that are recognized by RNase H when the strand is hybridized to the transcription product, (b) one or more nucleotide analogs located on 5′ terminal side of the region, (c) one or more nucleotide analogs located on 3′ terminal side of the region and (d) a total number of nucleotides and nucleotide analogs ranging from 8 to 35 nucleotides and (ii) the second nucleic acid strand comprises (a) nucleotides and optionally nucleotide analogs and (b) at least 4 consecutive RNA nucleotides.

Disclosed herein are methods and agents for the treatment of cancer using p53-independent apoptosis to reduce the number of p53-depleted or p53-mutated cancer cells that have amplified HER2 gene. Also disclosed herein are methods and agents for the treatment of HJ-R2-positive: cancer in individuals with Li-Fraumeni Syndrome.

Peptide nucleic acid (PNA) oligomers that target the β-globin gene and can increase the frequency of recombination of donor oligonucleotide at the site of a Sickle Cell Disease mutation are provided. Nanoparticle formulations for delivering the PNA oligomers and donor oligonucleotides, and potentiating agents for increase the frequency of recombination of the donor oligonucleotide are also provided. Methods of using the PNA oligomers, donor oligonucleotides, nanoparticles, and potentiating agents for treating Sickle Cell Disease are also provided.

The present invention relates to the fields of medicine and immunology. In particular, it relates to novel antisense oligonucleotides that may be used in the treatment, prevention and/or delay of Leber congenital amaurosis.

Triplex-forming peptide nucleic acid (PNA) oligomers having a γ-substitution in one or more residues of the Hoosteen binding segment are provided. γPNA-containing triplex-forming molecules can be used in combination with a donor DNA fragment to facilitate genome modification in vitro and in vivo. In some embodiments, the oligomers have between 1 and 50 inclusive γ-substituted PNA residues.

Provided herein are single-stranded tile (SST) structures prepared from and comprising single-stranded γPNA (ss-γPNA) strands, along with methods of making an SST structure from single-stranded γPNA (ss-γPNA) strands.

Disclosed herein are methods and agents for the treatment of cancer using p53-independent apoptosis to reduce the number of p53-depleted or p53-mutated cancer cells that have amplified HER2 gene. Also disclosed herein are methods and agents for the treatment of HER2-positive cancer in individuals with Li-Fraumeni Syndrome.

The present invention relates to the fields of medicine and immunology. In particular, it relates to novel antisense oligonucleotides that may be used in the treatment, prevention and/or delay of Leber congenital amaurosis.

Disclosed is a compound represented by formula (1) or a salt thereof:

##STR00001##

(wherein: “Base” represents an aromatic heterocyclic group which may have a substituent or an aromatic hydrocarbon ring group which may have a substituent; A.sup.1 represents a linear alkylene group; A.sup.2 represents a single bond or an alkylene group; X represents an alkylene group, —O— or —S(═O).sub.k—; R.sup.1 and R.sup.2 are the same as or different from each other and independently represent a hydrogen atom, etc.; and R.sup.3 represents an amino group which may have a substituent).