Oligonucleotide constructs are described, each comprising a functional element and a coding element, wherein the functional element comprises a functional sequence, the functional sequence comprising a sequence of nucleotides in which one or more, or each, nucleotide is modified and the coding element comprises a coding sequence, the coding sequence comprising a sequence of nucleotides which do not contain the modifications of the functional sequence, wherein the coding sequence encodes the sequence structure of the functional sequence.

The present invention relates to RNAi agents, e.g., dsRNA agents, targeting the angiotensin converting enzyme 2 (ACE2) gene. The invention also relates to methods of using such RNAi agents to inhibit expression of an ACE2 gene and to methods of treating or preventing an ACE2-associated disease, e.g., COVID-19, in a subject.

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.

The present invention relates to methods for the identification of anti-HIV miRNAs and anti-HIV pharmaceutical compounds using high-throughput screening methods, comprising: transfecting reporter cells with a panel of miRNAs, infecting the reporter cells with HIV, screening the cells to identify miRNAs that modulate HIV infection and identifying the specific pathways, nucleic acids and/or polypeptides that are targeted by the miRNAs. The invention further provides for the identification and screening of anti-HIV pharmaceutical compounds having known activity against the specific pathways, nucleic acids and/or polypeptides that are targeted by the miRNAs for efficacy in the treatment of HIV. The invention also provides for the use of miRNA mimics, miRNA inhibitors and pharmaceutical compounds (including oncology drugs and kinase inhibitors) in the treatment and/or prevention of HIV infection.

The present invention relates to a double-stranded oligonucleotide which can highly specifically and efficiently inhibit an amphiregulin expression and, preferably, a double-stranded oligonucleotide comprising a sequence in the form of RNA/RNA, DNA/DNA or DNA/RNA hybrid, a double-stranded oligonucleotide structure comprising the double-stranded oligonucleotide, nanoparticles comprising the double-stranded oligonucleotide structure, and a fibrosis or respiratory disease preventive or therapeutic use thereof.

The disclosure relates to double stranded ribonucleic acid interference (dsRNAi) agents and compositions targeting a microtubule-associated protein tau (MAPT) gene, as well as methods of inhibiting expression of a MAPT gene and methods of treating subjects having a MAPT-associated disease or disorder, e.g., Alzheimer's disease, frontotemporal dementia, progressive supranuclear palsy, or other tauopathies, using such dsRNAi agents and compositions.

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.

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 invention relates to double-stranded ribonucleic acid (dsRNA) compositions targeting the GPAM gene, as well as methods of inhibiting expression of GPAM, and methods of treating subjects that would benefit from reduction in expression of GPAM, such as subjects having a GPAM-associated disease, disorder, or condition, using such dsRNA compositions.

The present disclosure provides a preparation method of an artificial antibody. The preparation method includes the following steps: screening a target siRNA from a conserved gene or a microsatellite of a coronavirus, synthesizing a small hairpin RNA (shRNA) that has a loop by complementary sense and antisense strands of the siRNA, synthesizing an ACE2 capable of binding to a receptor-binding domain (RBD), and synthesizing the artificial antibody including an shRNA region and an ACE2 region by ligating the ACE2 to sense and antisense strands of the shRNA separately. The bivalent ACE2 is used for neutralization of the RBD and targeted delivery of the shRNA; the shRNA is ligated to the virus through the ACE2 and enters target cells with virus infection, thereby avoiding a side effect of non-specific delivery of the shRNA to uninfected cells, as well as resisting the variant strain and neutralizing the virus with the ACE2.