Abstract: siRNA molecules and pharmaceutical compositions containing siRNA molecules are provided for inhibiting expression of KRAS, RAF1 and mutant KRAS peptides or proteins. Methods of treatment of cancer are provided in which the pharmaceutical compositions are administered to a subject in need thereof. The cancer may be lung, colon, or pancreatic cancers, including non-small cell lung cancer (NSCLC). Combinations of siRNAs, packaged in nanoparticles with co-polymer carriers and delivered simultaneously to target cells, elicit an additive or synergistic effect to inhibit tumorous cell growth.

Abstract: Methods are provided for prevention and treatment of 2019 coronavirus (2019-nCoV; COVID-19) infections in mammals by prophylactic or therapeutic administration of pharmaceutical compositions known as STP908. STP908 administered intravenously, whether prophylactically or therapeutically, led to survival of 50 percent of the treatment group infected with 2019-nCoV. STP908 compositions and methods of making them have been previously disclosed, and comprise potent siRNA therapeutics formulated in a histidine-lysine polymeric carrier; the siRNA molecules in STP908 target and reduce or inhibit the expression of two genes of the 2019-nCoV genome: ORF1AB and N-protein, preventing or ameliorating COVID-19 symptoms.

Abstract: Delivery apparatus and methods for delivering a medical device into a patient's vasculature are disclosed. In some examples, a method includes inserting, into a patient, a distal end portion of a delivery apparatus including a radially compressed prosthetic valve mounted around a balloon, advancing the distal end through the patient's vasculature, and inflating the balloon to radially expand the prosthetic valve at a native heart valve. The delivery apparatus includes a handle, a first shaft and a second shaft extending from the handle, and a locking mechanism to prevent axial movement of the second shaft relative to first shaft. The second shaft extends coaxially through the first shaft and includes the balloon, the radially compressed prosthetic valve, and one or more radiopaque markers at a distal end portion. The first shaft includes an end piece covering a proximal portion of the balloon during the advancing of the delivery apparatus.

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: Methods are provided for prevention and treatment of 2019 coronavirus (2019-nCoV; COVID-19) infections in mammals by prophylactic or therapeutic administration of pharmaceutical compositions known as STP707, which compositions have been previously disclosed. These compositions comprise potent siRNA therapeutics formulated in a histidine-lysine polymeric carrier; the siRNA molecules target and reduce or inhibit TGF?1 and Cox2 gene expression, preventing or ameliorating COVID-19 symptoms.

Abstract: Methods of making and using nanoparticle pharmaceutical compositions comprising histidine-lysine copolymers are provided. The solutions spontaneously form nanoparticles when mixed with nucleic acids such as siRNA. Methods are provided where the pH of the nucleic acid solution is controlled prior to mixing leading to a reduction in nanoparticle diameter to a desirable range, typically 100-150 nm, and Polydispersity Index (PDI), both of which improve transport into target cells to improve the efficacy of gene silencing.

Abstract: Improved pharmaceutical nanoparticle compositions and improved methods for preparing the compositions comprising histidine-lysine copolymers and an acetate salt or phosphate anion are provided. The addition of acetate or phosphate anion to the histidine-lysine copolymer prior to mixing with a nucleic acid alters nanoparticle size and polydispersity index of the compositions and provides a more uniform particle size distribution.

Abstract: Methods are provided for improving the manufacture and use of pharmaceutical compositions comprising histidine-lysine copolymers and nucleic acids, which spontaneously form nanoparticles when mixed. The flow rate of mixing and the ratio of copolymer to siRNA strongly affect nanoparticle properties, including size and homogeneity of particles, resulting in greater efficacy in delivery to target cells. Further, an acidic pH of the siRNA solution, as well as the addition of acetate or phosphate salt to the histidine-lysine copolymer prior to mixing with the siRNA also contribute to lower nanoparticle diameters and more uniform particles (lower PDI).

Abstract: Compositions and methods are provided for the silencing of the NSD3 gene. Specifically, siRNA compositions are provided that contain siRNA molecules that target the wild-type NSD3 gene or the NSD3T1232A mutant. Methods for using these compositions for treating cancer also are provided.

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 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 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: 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: 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 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 present invention relates to compositions and methods for development of resistance-proof siRNA therapeutics for prevention and treatment of influenza viral infections. The compositions include a pharmaceutical composition comprising siRNA molecules that target conserved regions of an influenza virus gene and a pharmaceutically acceptable polymeric carrier. In one embodiment, the polymeric carrier condenses the molecules to form a nanoparticle.

Abstract: The invention provides siRNA compositions that (1) interfere with viral replication of human papillomavirus (HPV), herpes simplex virus (HSV), and human immunodeficiency virus (HIV) in mucosal tissues, such as genital tissues, and (2) treat fungal infections. The compositions include siRNA molecules that target HPV, complexed with a dendrimer that treats and prevents genital herpes (HSV) and HIV. The compositions also include siRNA molecules that target HPV, complexed with a histidine-lysine (HK) polymer that treats and prevent fungus infection. The combined formulations of siRNA and dendrimer provide treatment of the infections from HPVs, HSVs, and HIVs. The combined formulations of siRNA and HK polymer provide treatment of HPVs and fungus infections.

Abstract: The present invention relates to compositions and methods for development of resistance-proof siRNA therapeutics for prevention and treatment of influenza viral infections. The compositions include a pharmaceutical composition comprising siRNA molecules that target conserved regions of an influenza virus gene and a pharmaceutically acceptable polymeric carrier. In one embodiment, the polymeric carrier condenses the molecules to form a nanoparticle.