123results about "Special delivery" patented technology

To provide the use of a compound for manufacturing a reagent for efficient in vivo delivery of nucleic acid molecules, including small RNA, to a target organ and a target cell.SOLUTION: The invention provides the use of a compound derived naturally (including a traditional Chinese medicine extract) or synthetically for the manufacture of a nucleic acid delivery reagent, where the compound is represented, e.g., by the formula in the figure.SELECTED DRAWING: None

Delivery of oligonucleotides and other agents to tumor microenvironments is challenging due to their rapid clearance, nuclease susceptibility, and inability to traverse plasma membranes, impeding their effective use for the treatment of a variety of disorders. Disclosed herein is a self-agglomerating nanohydrogel and methods of delivering an agent as well as methods of treating cancer with the nanohydrogel.

The present disclosure relates to polypeptides, such as fibronectin type III (FN3) domains that can bind CD71, their conjugates, isolated nucleotides encoding the molecules, vectors, host-cells, as well as methods of making and using the same.

Compositions comprising miRNA (MSC-EV-miRNA) derived from mesenchymal stromal cell-derived extracellular vesicles and their use in subjects diagnosed with acute respiratory distress syndrome (ARDS) and other inflammatory diseases are disclosed herein. Also disclosed herein are methods for creating differential MSC-EV-miRNA profiles for any disease of interest (e.g., ARDS) and the use of miRNA profiles for creating miRNA-based therapies. Additional aspects of the disclosure relate to primer mixes for rapidly detecting specific miRNA profiles, and kits thereof.

The present disclosure provides a Lipid-Based Enhancement Agent being a compound of Formula (I), (II), (III), or (IV): or pharmaceutically acceptable salts thereof, and related conjugates. The present disclosure also relates to uses of the Lipid-Based Enhancement Agents and conjugates, e.g., in delivering nucleic acid and / or treating or preventing diseases.

This invention relates to an RNAi agent comprising a carrier structure and an interfering nucleic acid in its structure or pharmaceutically acceptable salt thereof. The invention also relates to a method of using the RNAi agent to inhibit AGT gene expression and a method of using the RNAi agent to prevent and treat AGT related diseases.

Alterations of the 5′GT splice motif or 3′AG splice motif result in severe missplicing and are prevalent in many genetic diseases, including cystic fibrosis (CF). While protein-targeted modulator therapies are currently available for treatment of CF, individuals with these canonical splice site variants (CSSVs) are among the ˜10% who remain untreated. The most common CF-causing variant in individuals of African descent is a CSSV, c.2988+1G>A. While >75% of individuals with a CSSV have a modulator eligible in trans allele, only 50% of the 450 individuals bearing c.2988+1G>A are eligible. Thus, there is a particular unmet need for a treatment for these individuals. CRISPR / Cas9-mediated adenine base editing (ABE) is an efficient and targeted genome editing method correct G>A variants. We electroporated NRCH-ABE8e mRNA and a previously optimized sgRNA to non-differentiated human primary nasal (HNE) or bronchial (HBE) epithelial cells from individuals with CF compound heterozygous for c.2988+1G>A. After differentiation of edited cells genomic editing and recovery of CFTR channel function were assessed. In primary HBEs and primary HNEs, we observed an allelic conversion to WT of 74.7% and 81.3%, respectively, at the +1 site. Interestingly, we also observed high levels of editing at adjacent adenines (+3, +7), which would have a modest effect on mRNA splicing (˜20% reduction). However, this did not preclude recovery of CFTR channel function. Compared to WT / WT HBEs and HNEs, unedited cells showed ˜5% function, while edited cells achieved >50% function. Since electroporation is not a translationally viable delivery approach, we investigated polymeric nanoparticle mediated delivery to both primary HBE and HNE cells by flow cytometry. GFP mRNA evaluated transfection efficiency and cell viability across three dosages (150, 75, 32.5 ng), four polymer-to-mRNA weight-to-weight ratios (60, 40, 30, 20) and three polymers (R, X, Y). HBEs transfected with polymers R & Y showed ˜57% transfection at 75 and 32.5 ng, with polymer X averaging ˜25% across the same dosages. Polymer Y showed slightly higher viability of HBEs vs. polymer R. HNEs in comparison achieved a maximum of ˜37% GFP transfection with polymers R & Y at 32.5 ng compared to a maximum of ˜22% with polymer X at the same dose, with 75-95% viability across all polymers. The ABE design reported here corrects c.2988+1G>A in airway epithelia with high efficiency when robust delivery is achieved. Given that nanoparticle optimization allowed successful delivery to >50% of cells, we anticipate clinically significant recovery of function in vivo by combining this ABE design with an optimized polymeric nanoparticle.

The present invention relates to methods and compositons comprising RNAi agents, e.g, double stranded RNA (dsRNA) agents, targeting the beta-catenin (CTNNB1) gene for treating CTNNB1 -associated disorders, such as cancer, e.g., hepatocellular carcinoma and colorectal cancer. The present invention also relates to combination therapies of RNAi agents, e.g., double stranded RNA (dsRNA) agents, targeting the beta-catenin (CTNNB1) gene, and one or more treatments and / or therapeutic agents, e.g., immunotherapeutic agents, e.g., one or more immune checkpoint inhibitors, e.g., a PD-1 inhibitor, e.g., an anti-PD-1 antibody, or antigen-binding fragment thereof, a PD-L1 inhibitor, a CTLA-4 inhibitor, and / or VEGF inhibitors, for treating a subject having a CTNNB1-associated disorder, such as cancer, e.g., hepatocellular carcinoma and colorectal cancer.

An antisense oligonucleotide (ASO) 14 to 20 nucleotides in length that specifically hybridizes with a gastrin mRNA molecule, wherein the ASO comprises at least one locked nucleic acid (LNA) nucleotide at each of the 5' and 3' termini.

Disclosed herein are compounds that include a lipid PK / PD modulator for in vivo delivery of an oligonucleotide-based agent, such as a double-stranded RNAi agent, to a specific cell type, such as CNS cells. The PK / PD modulators disclosed herein, when combined with an oligonucleotide-based therapeutic or diagnostic agent, such as an RNAi agent, can enhance delivery of the composition to a specific target cell and promote inhibition of gene expression in those cells.

The application provides a dsHpAGO1 for preventing and controlling holotrichia larvae and application thereof, and belongs to the field of biotechnology and agricultural application. The dsHpAGO1 in the application is synthesized by an HpAGO1 gene with a nucleotide sequence as shown in SEQ ID NO. 1 and dsRNA primers with nucleotide sequences as shown in SEQ ID NO. 3 to SEQ ID NO. 4. After the holotrichia larvae are injected with the dsHpAGO1 in the application, the expression amount of the HpAGO1 gene is significantly reduced compared with a control group, the interference efficiency is 95.53%, the holotrichia larvae grow and develop abnormally, and a large number of holotrichia larvae die, the mortality rate is 91.7%, and the silencing efficiency of the HpVAA gene is reduced by 42.6%. Therefore, the dsHpAGO1 in the application has great significance in the prevention and control of holotrichia larvae.

The present invention relates to recombinant adeno-associated virus (rAAV) delivery of polynucleotides for treating Duchenne Muscular Dystrophy resulting from the duplication of DMD exon 2. The invention provides rAAV products and methods of using the rAAV in the treatment of Duchenne Muscular Dystrophy.

This disclosure provides a method for inhibiting glycerol kinase (GK) for the treatment or prevention of diseases associated with elevated serum triglyceride (TAG) levels and metabolic dysfunction-related fatty liver disease (MASLD). Novel nucleic acids capable of inhibiting GK are also provided.

The present invention provides an oligodeoxynucleotide of unmethylated cytosine-phosphate-guanine dinucleotide and B lymphocytes bound thereto, which can target migration to diseased lymphoid organs and inhibit B lymphocytes activated under pathological conditions, thereby having a targeted therapeutic effect against pathological damage caused by B lymphocyte activation.

Aspects of the disclosure relate to complexes comprising a muscle-targeting agent covalently linked to a molecular payload. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload inhibits activity of a disease allele associated with muscle disease. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide or RNAi oligonucleotide.

The invention relates to inhibitory nucleic acids and rAAV-based compositions, methods and kits useful for treating Amyotrophic Lateral Sclerosis.

A composition comprising (a) a therapeutic agent or a pharmaceutically acceptable salt thereof; (b) a PEG-monoorthoester-lipid; (c) an amphiphilic lipid; (d) a cationic lipid and / or a beta-alanyl-prolyl-cysteine methyl ester; and optionally (e) a steroid and / or a ceramide and / or DOPE. The composition for use as a medicament.

The invention relates to Nano-in-micro (NIM) encapsulated bioactive therapeutic nucleic acid dry powder comprising lipid nanoparticles, the lipid nanoparticles comprising at least an ionizable cationic lipid, a helper lipid, a stealth lipid, and therapeutic nucleic acid, wherein the lipid nanoparticles are encapsulated in a pharmaceutically acceptable excipient, comprising at least one substance selected from the group consisting of monosaccharides, polysaccharides, sugar alcohols, (poly-)peptides, proteins, esters, urethanes, phosphoesters, phosphazenes, amino acids, surfactants, polymers. The invention also relates to the mass ratio of the therapeutic nucleic acid to the excipient is more than 0.10%, preferably between 0.90% and 1.30%.

The present invention relates to a dual-targeting siRNA agent comprising two distinct siRNAs targeting two different genes or their pharmaceutically acceptable salts, wherein the two distinct siRNAs or their salts are linked by a pharmaceutically acceptable ligand. The siRNA is a dsRNA composed of a sense strand and an antisense strand, and the two different genes are selected from a group consisting of angiotensinogen (AGT), proprotein convertase subtilisin / kexin type 9 (PCSK9), and human angiopoietin-like protein 3 (ANGPTL3). The present invention provides the application of the dual-targeting siRNA agent in the preparation of drugs for preventing or treating diseases associated with hypertension and / or dyslipidemia. The dual-targeting siRNA agent described in the present invention can effectively inhibit the expression of two target genes simultaneously in vivo, offering the advantages of strong non-antagonistic activity and high safety. The present invention also provides the siRNAs targeting corresponding genes for the aforementioned dual-targeting siRNA agent and their use for preventing or treating diseases associated with hypertension and / or dyslipidemia.

Provided is an antiangiogenic agent in the form of a vehicle, e.g., a nanoparticle associated (directly or indirectly) with at least one ocular angiogenesis growth factor aptamer, wherein said association labile to interaction between the aptamer and an ocular angiogenesis growth factor.

The present disclosure provides methods and compositions for using a novel class of glycan conjugates for modulating cell surface proteins and receptor complexes that can be used to engage signaling pathways within desired cell types. Such defined cell-targeting bioactive glycoligands are directed to cell engagement and activation in therapeutic applications.