Single-stranded RNA molecules comprise one or more internal, non-nucleotide spacers, covalently linked with nucleotide portions of the molecule are provided. The single-stranded RNA molecules function as guide or antisense strands that are capable of inhibiting gene expression via an RNA interference mechanism, and thus represent single-stranded RNAi agents. The single-stranded RNAi molecules can be used in methods for a variety of therapeutic, diagnostic, target validation, genomic discovery, genetic engineering, and pharmacogenomic applications.

The invention provides a single-stranded nucleic acid molecule of (A) or (B) containing a TGF-β1 gene expression inhibitory sequence. The single-stranded nucleic acid molecule (A) consists of region (Xc), linker region (Lx) and region (X) from the 5′-side to the 3′-side, wherein linker region (Lx) has a non-nucleotide structure containing at least one of a pyrrolidine skeleton and a piperidine skeleton, and at least one of region (X) and region (Xc) contains the expression inhibitory sequence. The single-stranded nucleic acid molecule (B) contains region (Xc), linker region (Lx), region (X), region (Y), linker region (Ly) and region (Yc) from the 5′-side to the 3′-side, wherein region (X) and region (Y) are linked to form inner region (Z), region (Xc) is complementary to region (X), region (Yc) is complementary to region (Y), linker region (Lx) and linker region (Ly) each have a non-nucleotide structure containing at least one of a pyrrolidine skeleton and a piperidine skeleton, and inner region (Z) contains the expression inhibitory sequence.

Compositions and methods for enhancing targeted gene editing and methods of use thereof are disclosed. In the most preferred embodiments, gene editing is carried out utilizing a gene editing composition such as triplex-forming oligonucleotides, CRISPR, zinc finger nucleases, TALENS, or others, in combination with a gene modification potentiating agent such as stem cell factor (SCF), a CHK1 or ATR inhibitor, or a combination thereof. A particular preferred gene editing composition is triplex-forming peptide nucleic acids (PNAs) substituted at the γ position for increased DNA binding affinity. Nanoparticle compositions for intracellular delivery of the gene editing composition are also provided and particular advantageous for use with in vivo applications.

Aspects of the present invention include the production and use of chemically modified RNAi agents (e.g., shRNAs) in gene silencing applications. The chemically modified RNAi agents disclosed herein have reduced immunostimulatory activity, increased serum stability, or both, as compared to a corresponding RNAi agent not having the chemical modification. Compositions containing chemically modified RNAi agents according to aspects of the present invention (including pharmaceutical compositions) and kits containing the same are also provided.

Aptamers that bind PDGF and aptamers that bind VEGF are provided. In addition, aptamer constructs comprising a PDGF aptamer and a VEGF aptamer are provided. Pharmaceutical compositions comprising the aptamers and aptamer constructs are provided, as well as methods of treating conditions using the aptamers and aptamer constructs.

The present invention relates to a method for determining the amount of an oligonucleotide present in a powdered form. The method does not require the experimental determination of the extinction coefficient of the oligonucleotide or the serial dilution and A260 measurement. The method is, for example, applicable to modified oligonucleotides including 2′ sugar-modified oligonucleotides, phosphorothioate oligonucleotides, reporter labelled oligonucleotides, and conjugated oligonucleotides.

The present disclosure relates generally to cleavable linkers and uses thereof.

The disclosure is generally related to oligonucleotides having a hairpin-like structure, nanoparticles comprising the same, and methods of using the same.

The present invention relates to methods and compositions for editing an RS1 polynucleotide, e.g., an RS1 polynucleotide comprising a SNP associated with X-linked retinoschisis (XLRS). The invention also relates to methods and compositions for treating or preventing XLRS in a subject.

The present disclosure provides oligomeric compound comprising a modified oligonucleotide having a central region comprising one or more modifications. In certain embodiments, the present disclosure provides oligomeric compounds having an improved therapeutic index or an increased maximum tolerated dose.