Described herein are RNA-based antisense therapeutics to target antibiotic resistant bacteria. The antisense therapeutics disclosed herein can be useful in re-sensitizing drug-resistant bacteria to antibiotics, as well as developing antibiotics that have bactericidal or bacteriostatic effects on the drug-resistant bacteria or are capable of preventing emergence of antibiotic resistance. Also described herein are methods for re-sensitizing a subject to one or more antibiotics in need thereof, methods for identifying target genes involved in adaptive antibiotic resistance in bacteria, and methods for developing antibacterial antisense therapeutics.

Compounds, compositions and methods are provided for modulating the expression and function of small non-coding RNAs. The compositions comprise oligomeric compounds, targeted to small non-coding RNAs. Methods of using these compounds for modulation of small non-coding RNAs as well as downstream targets of these RNAs and for diagnosis and treatment of disease associated with small non-coding RNAs are also provided.

A photocaged DNA nano-tweezer and methods of using said photocaged DNA nano-tweezer are described. In particular, provided herein is a DNA nano-tweezer comprising a hairpin with a single-stranded loop that comprises a first arm and a second arm; and a trigger strand complementary to the single-stranded loop and comprising at least one photocaged residue with a protecting group.

The present invention provides compositions and methods for treating cancer with peptide nucleic acid agents. In some embodiments, the present invention provides methods and compositions relating to peptide nucleic acid agents that target oncogenes. For example, the present invention provides compositions, including pharmaceutical compositions, comprising agents specific for BRAF V600E inhibition, or fragments or characteristic portions thereof. The present invention further provides various therapeutic and/or diagnostic methods of using BRAF V600E specific peptide nucleic acid agents and/or compositions.

Compositions and methods of use thereof for delivering nucleic acid cargo into cells are provided. The compositions typically include (a) a 3E10 monoclonal antibody or an antigen binding, cell-penetrating fragment thereof; a monovalent, divalent, or multivalent single chain variable fragment (scFv); or a diabody; or humanized form or variant thereof, and (b) a nucleic acid cargo including, for example, a nucleic acid encoding a polypeptide, a functional nucleic acid, a nucleic acid encoding a functional nucleic acid, or a combination thereof. Elements (a) and (b) are typically non-covalently linked to form a complex.

Provided are structural properties of double-stranded RNA molecules for inducing RNA interference, and more specifically, a novel nucleic acid molecule structure for inducing RNAi with improved stability, and a use thereof. A nucleic acid molecule for inducing RNAi provided herein is capable of significantly improving stability of a double-stranded RNA molecule in vivo while maintaining inhibition efficiency for a target gene, and therefore, as a expandable platform for targeting various genes, the RNA nucleic acid molecule is expected to replace siRNA molecules in the art, and be usefully utilized in the field of diagnosis or treatment of various diseases in research and clinical fields.

The invention provides an artificial sgRNA and a CRISPR/Cas9 system by combining the artificial sgRNA and Cas9. Activity of the sgRNA can be retained even when a nucleotide linker region for forming a single strand by linking the 3′-terminal of crRNA and the 5′-terminal of tracrRNA in sgRNA is substituted with an amino acid derivative linker, when the linker region existing between stem-loop 1 and stem-loop 2 of tracrRNA and/or the loop portion of stem-loop 2 are/is substituted with an amino acid derivative linker, or when an amino acid derivative linker is added/inserted into the vicinity of the 5′-terminal and/or the 3′-terminal of sgRNA. Stability in vivo can be improved by introducing one or more amino acid derivative linkers into the sgRNA.

Peptide nucleic acid (PNA) oligomers having one or more hydroxymethyl γ-substitutions, also referred to herein as “.sup.serγPNA”, are provided. The hydroxymethyl γ-substitution preserves and amplifies the helical preorganization that is valuable for DNA duplex invasion by the oligomer. .sup.serγPNA-containing triplex-forming molecules can be used in combination with a donor DNA fragment to facilitate genome modification in vitro and in vivo.

In one aspect, the invention relates to a method of loading exosomes with oligonucleotide cargo, by incubating an oligonucleotide comprising one or more hydrophobic modifications with a population of exosomes for a period of time sufficient to allow loading of the exosomes with the oligonucleotide. Exosomes loaded with hydrophobically modified oligonucleotide cargo, and uses thereof, are also provided.

The present invention provides the peptide nucleic acid derivative which targets 3′ splice site of the human MLPH pre-mRNA “exon 2”. The peptide nucleic acid derivatives in the present invention strongly induce splice variants of the human MLPH mRNA in cell and are very useful to treat diseases or conditions of skin pigmentation associated with the human MLPH protein.