A double-stranded nucleic acid complex that can have an excellent activity is provided. In one embodiment, the present invention relates to a double-stranded nucleic acid complex having a first nucleic acid strand and a second nucleic acid strand. The first nucleic acid strand is capable of hybridizing to at least part of a target gene or a transcription thereof, has an antisense effect on the target gene or transcription product thereof, and has at least two morpholino nucleic acids The second nucleic acid strand has a base sequence complementary to the first nucleic acid strand. The first nucleic acid strand is annealed to the second nucleic acid strand.

Described herein are molecules for editing a cell. The molecules described herein generally comprise the following covalently-linked components and a nucleic acid encoding a guide RNA (gRNA) sequence targeting a target region in a cell and a region homologous to the target region comprising a change in sequence relative to the target region.

Methods and compositions for modulation of the activity of alpha thalassemia/mental retardation syndrome X-linked (ATRX), e.g., modulation of DNA-ATRX or RNA-ATRX interactions, and methods for identifying and using compounds that modulate DNA-ATRX or RNA-ATRX interactions, as well as the compounds themselves.

The invention provides for systems, methods, and compositions for manipulation of sequences and/or activities of target sequences. Provided are vectors and vector systems, some of which encode one or more components of a CRISPR complex, as well as methods for the design and use of such vectors. Also provided are methods of directing CRISPR complex formation in eukaryotic cells and methods for selecting specific cells by introducing precise mutations utilizing the CRISPR/Cas system.

The present invention provides a non-naturally occurring composition comprising a CRISPR nuclease comprising a sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 3 or a nucleic acid molecule comprising a sequence encoding the CRISPR nuclease.

The invention provides methods of selecting guide RNA sequences, and the use of such sequences in CRISPR-Cas gene editing of a target sequence. In particular, the invention relates to a method of selecting guide RNA sequences, based on the determined frequencies of editing outcomes, which in one case result in low mosaicism and in another case result in large deletions or knockouts.

A vector production system is provided. The system comprises recombinant cells designed to encode at least a first recombinase under the control of an inducible promoter and the cells include an expression vector encoding a nucleic acid of interest within the regulatory elements of the expression vector which are flanked on either side by a target sequence for at least the first recombinase. The vector production system provides an efficient one-step process for producing linear or circular covalently closed vectors that incorporate a nucleic acid sequence of interest.

The present invention provides a novel siRNA specifically inhibiting the expression of IL-23 and a pharmaceutical composition comprising the siRNA, specifically a double stranded RNA comprising a sense strand and an antisense strand wherein each strand has 19 to 30 nucleotides and comprises the base sequence selected from SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5 or SEQ ID NO: 6 or a complementary base sequence thereof and a pharmaceutical composition comprising the double stranded RNA.

The present application provides guide RNAs and genome-editing complexes or nanoparticles that are useful for specifically targeting a mutated KRAS. Exemplary genome-editing complexes or nanoparticles comprise cell-penetrating peptides, and optionally a DNA nuclease (such as Cas9) or a polynucleotide encoding the DNA nuclease.

Provided are compounds, methods, and pharmaceutical compositions for reducing the amount or activity of UBE3A-ATS, the endogenous antisense transcript of ubiquitin protein ligase E3A (UBE3A) in a cell or subject, and in certain instances increasing the expression of paternal UBE3A and the amount of UBE3A protein in a cell or subject. Such compounds, methods, and pharmaceutical compositions are useful to ameliorate at least one symptom or hallmark of a neurogenetic disorder. Such symptoms and hallmarks include developmental delays, ataxia, speech impairment, sleep problems, seizures, and EEG abnormalities. Such neurogenetic disorders include Angelman Syndrome.