Methods and compositions are provided for nuclease-mediated gene editing of primary cells without the use of viral mediated delivery. Methods of treatments using edited primary cells are also provided.

An objective of the present invention is to provide a chemically-modified siRNA that has polydeoxyadenylic acid added to the 5′ end of the sense strand, and, when complexed with schizophyllan, is high in resistance against RNase and moreover effectively exhibits RNAi activity. To achieve the objective, in the chemically-modified siRNA with polydeoxyadenylic acid added to the 5′ end of the sense strand, specific chemical modification is performed for dinucleotide sequences of CA, UA, and UG in the base sequence of the sense strand and dinucleotide sequences of CA, UA, and UG in the base sequence at and after the eighth base from the 5′ end of the antisense strand.

The invention relates to double-stranded ribonucleic acid (dsRNA) compositions targeting the ANGPTL3 gene, as well as methods of inhibiting expression of ANGPTL3 and methods of treating subjects having a disorder of lipid metabolism, such as hyperlipidemia or hypertriglyceridemia, using such dsRNA compositions.

The present invention relates to compounds, compositions, and methods for the study, diagnosis, and treatment of traits, diseases and conditions that respond to the modulation of gene expression and/or activity, and/or modulate a gene expression pathway. Specifically, the invention relates to double-stranded nucleic acid molecules including small nucleic acid molecules, such as short interfering nucleic acid (siNA) molecules that are capable of mediating or that mediate RNA interference (RNAi) against target gene expression.

The present disclosure provides DNA-guided CRISPR systems; polynucleotides comprising DNA, RNA and mixtures thereof for use with CRISPR systems; and methods of use involving such polynucleotides and DNA-guided CRISPR systems.

The present invention relates to compounds, compositions, and methods for the study, diagnosis, and treatment of traits, diseases and conditions that respond to the modulation of gene expression and/or activity, and/or modulate a gene expression pathway. Specifically, the invention relates to double-stranded nucleic acid molecules including small nucleic acid molecules, such as short interfering nucleic acid (siNA) molecules that are capable of mediating or that mediate RNA interference (MAO against target gene expression.

The present disclosure provides oligomeric compounds (including oligomeric compounds that are antisense agents or portions thereof) comprising a modified oligonucleotide having at least one modified internucleoside linking group.

Compositions and methods for down modulating target gene expression are disclosed.

A composition including a phosphorothioate oligonucleotide and at least one fatty acid and/or at least one emulsifying agent, where the composition is sterile and where the composition includes at least one agent including a thiol group and at least one phosphate compound, and the composition can be an ophthalmic composition. The present invention also relates to a method for obtaining the same and to the therapeutic use thereof.

The present invention relates to antisense oligonucleotides that are capable of modulating expression of Tau in a target cell. The oligonucleotides hybridize to MAPT mRNA. The present invention further relates to conjugates of the oligonucleotide and pharmaceutical compositions and methods for treatment of Tauopathies, Alzheimer's disease, fronto-temporal dementia (FTD), FTDP-17, progressive supranuclear palsy (PSP), chronic traumatic encephalopathy (CTE), corticobasal ganglionic degeneration (CBD), epilepsy, Dravet syndrome, depression, seizure disorders and movement disorders.