CRISPR/Cas-related compositions and methods which provide for efficient gene editing of eukaryotic cells using modified gRNAs.

The present invention relates to: a double-stranded oligonucleotide which can highly specifically and efficiently inhibit the proliferation of Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2), preferably a double-stranded oligonucleotide comprising a sequence in the form of RNA/RNA, DNA/DNA or a DNA/RNA hybrid; a double-stranded oligonucleotide structure and nanoparticles comprising the double-stranded oligonucleotide; and a use thereof for treating COVID-19.

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 invention relates to methods and compositions for editing an ASS1 polynucleotide, e.g., an ASS1 polynucleotide comprising a SNP associated with Citrullinemia Type 1. The invention also relates to methods and compositions for treating or preventing Citrullinemia Type 1 in a subject.

Disclosed is a modified siRNA with a reduced off-target activity. The siRNA comprises a sense strand and an antisense strand, wherein the antisense strand contains a chemical modification as represented by formula (I) or a tautomeric modification thereof in at least one nucleotide position from position 2 to position 8 of 5′ region thereof. A conjugate, a pharmaceutical composition, a cell or a kit containing the siRNA, and the medical use of the siRNA, the conjugate and/or the pharmaceutical composition thereof are also disclosed. Further disclosed are compounds as represented by formula (II) and formula (III) or tautomers thereof, and preparation methods therefor.

The invention relates to iRNA, e.g., double stranded ribonucleic acid (dsRNA), compositions targeting the complement factor C3 gene, and methods of using such iRNA, e.g., dsRNA, compositions to inhibit expression of a C3 gene and to treat subjects having a complement component C3-associated disease, e.g., paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), atypical hemolytic uremic syndrome (aHUS), neuromyelitis optica (NMO), multifocal motor neuropathy (MMN), myasthenia gravis (MG), and C3 glomerulonephritis.

Protecting oligonucleotides are provided. Protecting oligonucleotides with 5 and/or 3 conjugated moieties are provided. Protecting oligonucleotides with chemical modifications are provided. Methods of using the protecting oligonucleotides for genome editing with a CRISPR nuclease and kits for performing the same are also provided.

Protecting oligonucleotides are provided. Protecting oligonucleotides with 5 and/or 3 conjugated moieties are provided. Protecting oligonucleotides with chemical modifications are provided. Methods of using the protecting oligonucleotides for genome editing with a CRISPR nuclease and kits for performing the same are also provided.

The invention relates to iRNA, e.g., double stranded ribonucleic acid (dsRNA), compositions targeting the complement factor C3 gene, and methods of using such iRNA, e.g., dsRNA, compositions to inhibit expression of a C3 gene and to treat subjects having a complement component C3-associated disease, e.g., paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), atypical hemolytic uremic syndrome (aHUS), neuromyelitis optica (NMO), multifocal motor neuropathy (MMN), myasthenia gravis (MG), and C3 glomerulonephritis.

The present disclosure generally relates to systems, methods and compositions for use in Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cpf1 genome editing systems.