Abstract: The present invention relates to a siRNA drug, a pharmaceutical composition, a siRNA-small molecule drug conjugate, and the application thereof. The siRNA molecules block the life cycle of virus replication by targeting and inhibiting the expression of key genes for influenza viruses, reduce viral infection, and ultimately clear the viruses. The present invention provides a drug based on the siRNA. The drug can be atomized into liquid droplets through an atomizing device, and the liquid droplets reach the lower respiratory tract and the lung by inhalation, so as to inhibit the replication of the influenza viruses. The pharmaceutical composition of the present invention can exert a synergistic antiviral effect through different mechanisms of action.

Abstract: A pharmaceutical composition, comprises micro RNAs with or without chemical modification, and a carder suitable for delivery in vivo, the carrier is a branched histidine-lysine polypeptide or modified compound thereof. The pharmaceutical composition is capable of inhibiting the growth of colon cancer by inducing programmed death of cancer cell and further be used for the manufacture of a targeted drug for colorectal cancer treatment.

Abstract: Pharmaceutical constructs containing a Peptide Docking Vehicle (PDoV) covalently linked to: (a) a targeting moiety; and (b) a first therapeutic nucleic acid, are provided, where the therapeutic nucleic acid inhibits replication of Hepatitis B virus (HBV). Methods of using the constructs for treating HBV in subjects also are provided.

Abstract: siRNA sequences for inhibiting TGF? and Cox-2 gene expression are provided. Methods for treatment of skin cancers, in which pharmaceutical compositions or containing these siRNA agents and complexes, are further provided, in particular, for treating squamous cell carcinoma (isSCC) and/or basal cell carcinoma (BCC). TGF? and Cox-2 have each been implicated in driving cancer progression. TGF? is upregulated in a number of tumor types and plays a role in stimulating cancer-associated fibroblast development. Cox-2 upregulation plays a negative role in inducing inflammation and converting active T-cells to inactive T-reg cells. Co-delivery of the two siRNAs into the same cell at the same time silences of both targets at the same time results in antitumoral activity.

Abstract: The techniques of the present disclosure provide a method of inhibiting tumor growth in a tissue of a mammal. The method includes administering to the mammal a therapeutically effective amount of a composition comprising an siRNA molecule that binds to an mRNA that codes for TGF?1 protein, an siRNA molecule that binds to an mRNA that codes for VEGFR2 protein, and a pharmaceutically acceptable carrier comprising a pharmaceutically acceptable polypeptide polymer. The techniques of the present disclosure also provide for additional methods for using this composition.

Abstract: The current invention provides a method of activating fibroblast and myofibroblast apoptosis in a tissue of a mammal, comprising administering to the tissue a therapeutically effective amount of a composition comprising an siRNA molecule that binds to an mRNA that codes for TGFB1 protein in a mammalian cell, an siRNA molecule that binds to an mRNA that codes for COX-2 protein in a mammalian cell, and a pharmaceutically acceptable carrier comprising a pharmaceutically acceptable histidine-lysine polymer. The invention also provides additional methods for using this composition.

Abstract: Compositions and methods are provided for potent mRNA vaccines for prevention and treatment of 2019 novel Coronavirus (2019-nCoV) infections. The compositions include a pharmaceutical composition containing one or more mRNA molecules encoding spike protein epitopes, including mutated epitopes, or mRNA cocktails that encode critical viral genes together with pharmaceutically acceptable polymeric nanoparticle carriers and liposomal nanoparticle carriers. Methods for stimulating system immune responses and treatment are provided, including subcutaneous, intraperitoneal and intramuscular injections.

Abstract: siRNA compositions are provided that contain gemcitabine (GEM) in place of cytosine moieties within the siRNA sequence. Pharmaceuticals compositions containing these siRNA molecules, and methods of using the compositions for treating diseases such as cancer are provided.

Abstract: A novel nucleic acid delivery system is provided containing a linear histidine-lysine rich cysteine-containing peptide bearing a targeting function, and a four branched histidine-lysine rich polypeptide. The delivery system includes a nucleic acid, such as an siRNA. The components form a nanoparticle complex through multiple non-covalent interactions between the phosphates of siRNA and histidine/lysine of the polypeptide, with reduced toxicity. The stable complex selectively delivers the genetic material to cells. The targeting function enhances the efficiency of the nucleic acid delivery and transfection. Carrier molecules also are provided that have the ability to deliver a therapeutic molecule to a specific cell within a tissue in the body. The carrier molecule is modified with a targeting ligand capable of binding to specific receptors present or upregulated on the cell to be targeted. The therapeutic molecule is an siRNA, miRNA, or other oligonucleotide.

Abstract: Compositions and methods are provided for silencing the Sulf2 and/or GPC3 genes in vivo. Potent siRNA sequences are provided that silence regions of the Sulf2 and GPC3 genes that are identical in human, mice and non-human primates. Combinations of siRNAs also are provided that result in additivity or synergy with silencing of Sulf2 and/or GPC3. Silencing SULF2+TGF?1 showed a dramatic effect against cancer growth in vitro and in vivo.

Abstract: Compositions containing an anti-TGF-? siRNA molecule and an anti-PDL1 siRNA molecule are provided. Methods of using these compositions to treat cancer also are provided.

Abstract: The present invention relates to compositions and methods for siRNA therapeutics for prevention and treatment of Middle East Respiratory Syndrome Corona Virus (MERS-CoA) infections. The compositions include a pharmaceutical composition comprising siRNA cocktails that target viral genes and pharmaceutically acceptable polymeric nanoparticle carriers and liposomal nanoparticle carriers.

Abstract: The invention relates to the targeted delivery of therapeutic molecules to organs, tissues, and cells of humans and other mammals. The invention is directed to a chemical construct for delivering such therapeutic molecules and to methods of making and using the constructs.

Abstract: Compositions and methods are provided for potent mRNA vaccines for prevention and treatment of 2019 novel Coronavirus (2019-nCoV) infections. The compositions include a pharmaceutical composition containing one or more mRNA molecules encoding spike protein epitopes, including mutated epitopes, or mRNA cocktails that encode critical viral genes together with pharmaceutically acceptable polymeric nanoparticle carriers and liposomal nanoparticle carriers. Methods for stimulating system immune responses and treatment are provided, including subcutaneous, intraperitoneal and intramuscular injections.

Abstract: The present invention provides certain pharmaceutical molecules and compositions and methods of using them to treat cancer. The molecules are small interfering RNA (siRNA) molecules that inhibit TGF-beta 1 and Cox2 in humans and other mammals, which are used alone or in combination with immune checkpoint inhibitors, to treat cancer.

Abstract: Compositions and methods for development of potent siRNA therapeutics for prevention and treatment of Corona Virus (2019-nCoV; COVID-19) infections are provided. The compositions include a pharmaceutical composition comprising siRNA cocktails that target critical viral genes and pharmaceutically acceptable polymeric nanoparticle carriers and liposomal nanoparticle carriers. Administration methods for prevention and treatment are provided, including airway instillation, subcutaneous injections and nebulizer aerosolization.

Abstract: Peptide docking vehicle compositions containing a therapeutic compound, such as an siRNA molecule, and a targeting ligand are provided, together with methods for their preparation and use. The compositions and methods allow targeted cell/tissue delivery of the therapeutic compound to a subject by linking a targeting ligand to the compound to provide enhanced therapeutic benefit. The subject may be an animal or a human.

Abstract: The present invention relates to compositions and methods for siRNA therapeutics for prevention and treatment of Middle East Respiratory Syndrome Corona Virus (MERS-CoV) infections. The compositions include a pharmaceutical composition comprising siRNA cocktails that target viral genes and pharmaceutically acceptable polymeric nanoparticle carriers and liposomal nanoparticle carriers.

Abstract: The present invention provides certain peptides and polypeptides useful in the preparation of nanoparticles for delivering nucleic acids and pharmaceutical drugs to mammalian cells and to humans and other mammals. It further provides methods for making the peptides, polypeptides, and nanoparticles and methods for using the nanoparticles.

Abstract: The current invention provides a method of activating fibroblast and myofibroblast apoptosis in a tissue of a mammal, comprising administering to the tissue a therapeutically effective amount of a composition comprising an siRNA molecule that binds to an mRNA that codes for TGFB1 protein in a mammalian cell, an siRNA molecule that binds to an mRNA that codes for COX-2 protein in a mammalian cell, and a pharmaceutically acceptable carrier comprising a pharmaceutically acceptable histidine-lysine polymer. The invention also provides additional methods for using this composition.