The disclosure provides tandem arrays of CRISPR RNAs and methods of use.

The present invention provides mesenchymal stem cells (MSCs) and extracellular vesicles comprising exogenous membrane embedded proteins. Pharmaceutical compositions comprising MSCs and extracellular vesicles are also provided. The present invention further provides a method of treating, preventing or ameliorating a viral infection, inflammation, and/or tissue fibrosis.

The present embodiments provide methods, compounds, and compositions useful for inhibiting or reducing SARS-CoV-2 replication, infectivity, viral titer, or viral load, which can be useful for preventing or treating COVID-19 in an individual.

Described herein are compositions defective SARS-CoV-2 constructs and particles that can interfere with or block infection of uninfected cells and methods for generating such defective SARS-CoV-2 constructs and particles. The compositions and methods described herein are useful for treatment of SARS-CoV-2 infections.

The present invention relates to specific reverse micelle system of the invention which allows the administration and intracellular delivery of unmodified oligonucleotide, such as siRNA, targeting one or more genes of the SARS-CoV-2 virus. The reverse micelle system of the invention is thus particularly useful for the treatment of the viral pathology linked to the SARS-CoV-2 virus.

Provided is a modified double-stranded oligonucleotide, in which the sense strand comprises a nucleotide sequence 1, the anti-sense strand comprises a nucleotide sequence 2, the nucleotide sequences 1 and 2 are both 19 nucleotides in length, and in the direction from 5′ end to 3′ end, nucleotides at positions 7, 8 and 9 of the nucleotide sequence 1 and nucleotides at positions 2, 6, 14 and 16 of the nucleotide sequence 2 are all fluoro-modified nucleotides, and each nucleotide at other positions is independently one of non-fluoro-modified nucleotides. Further provided are a pharmaceutical composition and a conjugate comprising the oligonucleotide, and pharmaceutical use thereof.

The present invention provides gene silencing agents that are capable of silencing the expression of the Coronavirus gene(s), e.g., SARS-CoV-2, both in vitro and in vivo. The present invention further provides general and specific compositions and methods of using such compositions that can be used to reduce specific SARS-CoV-2 protein levels or SARS-CoV-2 titers, in a subject, e.g., a mammal such as a human, for research or therapeutic purposes, for example to manage or treat conditions related to Coronavirus infection, e.g., COVID-19.

An RNAi molecule, the RNAi molecule, vector and composition including the RNAi molecule and method of using same, wherein the RNAi molecule includes a dsRNA sequence of from about 15 to about 60 base pairs, capable of decreasing expression of a SARS-CoV-2 gene.

Disclosed herein are embodiments of a compound useful for treating or preventing betacoronavirus infections such as SARS-Cov-2 infections. Also disclosed is a method for administering the compound to a subject, particularly a human subject, to treat or prevent a betacoronavirus infection in the subject. The compound can comprise an oligomer comprising a nucleic acid base sequence that is antisense to at least a portion of a SARS-CoV-2 genomic RNA, and can comprise a sequence present in the 5′ UTR and first 20 nt of coding sequence of the SARS-CoV-2 genomic RNA. The compound also can contain a peptide sequence. In some embodiments, the compound is a peptide-conjugated phosphorodiamidate morpholino oligomer (PPMO).

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.