Antisense oligonucleotides (ASOs) that disrupt RNA-RNA interactions of influenza virus genome segments that are required for virus packaging are described. The ASOs can be used to inhibit influenza A virus replication in vitro and in vivo. Use of the ASOs for the treatment of a subject with an influenza virus infection is also described.

The present invention relates to antisense oligonucleotides that modulate the expression of and/or function of a Reprogramming factor, in particular, by targeting natural antisense polynucleotides of a Reprogramming factor. The invention also relates to the identification of these antisense oligonucleotides and their use in treating diseases and disorders associated with the expression of Reprogramming factors.

Provided are peptide nucleic acid derivatives targeting the 5 splice site of exon 5 within the human androgen receptor pre-mRNA. The peptide nucleic acid derivatives potently induce splice variants of the androgen receptor mRNA in cells, and are useful to safely treat dermatological indications or conditions involving androgenic activity upon topical administration.

The disclosure provides novel methods and compositions for gene editing. In particular, the disclosure relates to compositions and methods of making modified nucleic acid donor templates for highly efficient and precise gene editing.

The current invention provides peptide nucleic acid derivatives targeting the 3 splice site of exon 4 in the human SCN9A pre-mRNA. The peptide nucleic acid derivatives potently induce SCN9A mRNA splice variant(s) lacking the SCN9A exon 4 in cells, and are useful to safely treat pains or conditions involving Na.sub.v1.7 activity.

Provided are peptide nucleic acid derivatives targeting a 3 splice site of the human SNAP25 pre-mRNA. The peptide nucleic acid derivatives potently induce at least a splice variant of the human SNAP25 mRNA in cells, and are useful to safely treat dermatological indications or conditions involving the expression of the human SNAP25 protein by topical administration.

A peptide nucleic acid derivative of Formula I is provided to tightly bind to a splice site within a pre-mRNA in a sequence specific manner. Given with excellent cell membrane permeability and strong affinity for RNA, the said peptide nucleic acid derivative induces exon skipping in cells treated with the peptide nucleic acid at sub-femtomolar concentration as naked oligonucleotide. The said compound shows therapeutic activity in subjects upon systemic administration even at 1 g/Kg or less, and therefore is useful to treat a disease or symptom at affordable treatment cost.

The disclosure provides novel methods and compositions for gene editing. In particular, the disclosure relates to compositions and methods of making modified nucleic acid donor templates for highly efficient and precise gene editing.

The present invention relates to antisense oligonucleotides that modulate the expression of and/or function of a Collagen gene, in particular, by targeting natural antisense polynucleotides of a Collagen gene. The invention also relates to the identification of these antisense oligonucleotides and their use in treating diseases and disorders associated with the expression of Collagen genes.

This invention pertains to the field of biopolymer-loaded (where the biopolymer(s) are active pharmaceutical ingredient(s) (API(s)) polymer-based nanoparticles formulated, for example, for curative, therapeutic prophylactic and/or diagnostic applications. The polymer used to formulate the nanoparticles can be any biodegradable synthetic polymer or combination of polymers, including combinations of PLGA and PEG. Biopolymers used as active pharmaceutical ingredients (API) can include natural and unnatural nucleic acids such as DNA, RNA and LNA. Biopolymers used as active pharmaceutical ingredients (APIs) can also include neutral and positively charged nucleic acid mimics (NPNAM) such as for example, peptide nucleic acids, morpholinos, pyrrolidine-amide oligonucleotide mimics, morpholinoglycine oligonucleotides and methyl phosphonates and derivatives thereof. In some embodiments, the nanoparticles are loaded with both nucleic acids and NPNAMs as the APIs. Nanoparticles so formulated can be used in curative, therapeutic, prophylactic and/or diagnostic applications. Certain preferred nanoparticles, formulation methodologies, de-formulation methodologies and apparatus are also disclosed.