Compositions and methods relating to modulating thermogenic regulation are disclosed. The compositions and methods can be used to treat diseases or conditions such as obesity or cardiometabolic disorders such as type 2 diabetes mellitus, NAFLD and NASH. Compositions include an adipocyte-targeting composition that includes a therapeutic agent capable of modulating thermogenic regulation, a targeting element facilitating cellular uptake and delivery of the therapeutic agent to a targeted adipocyte, and liposomal particles comprising sphingomyelin, DMPC, and cholesterol, wherein the liposomal particles enhance intra-cellular penetration of the therapeutic agent and protect the therapeutic agent from degradation.

Described are RNAi agents, compositions that include RNAi agents, and methods for inhibition of a Mucin 5AC (MUC5AC) gene. The MUC5AC RNAi agents and RNAi agent conjugates disclosed herein inhibit the expression of an MUC5AC gene. Pharmaceutical compositions that include one or more MUC5AC RNAi agents, optionally with one or more additional therapeutics, are also described. Delivery of the described MUC5AC RNAi agents to pulmonary epithelial cells, in vivo, provides for inhibition of MUC5AC gene expression and a reduction in MUC5AC production, which can provide a therapeutic benefit to subjects, including human subjects, for the treatment of various diseases including mucoobstructive lung disease such as severe asthma and various cancers.

The present disclosure relates to RNAi agents, e.g., double stranded RNAi agents, able to inhibit xanthine dehydrogenase (XDH) gene expression. Also disclosed are pharmaceutical compositions that include XDH RNAi agents and methods of use thereof. The XDH RNAi agents disclosed herein may be conjugated to targeting ligands to facilitate the delivery to cells, including to hepatocytes. Delivery of the XDH RNAi agents in vivo provides for inhibition of XDH gene expression. The RNAi agents can be used in methods of treatment of diseases, disorders, or symptoms mediated in part by XDH gene expression, such as gout and hyperuricemia.

The invention concerns lipid assemblies, liposomes having an outer surface comprising a mixture of anionic and cationic moieties; wherein at least a portion of the cationic moieties are imino moieties that are essentially charged under physiological conditions, and their use for serum resistant transfection of cells.

The invention is directed to antibacterial compositions comprising bacteria modified to comprise phasmids engineered to deliver of CRISPR RNAs and methods for their use.

The present disclosure provides one or more amino lipids such as an amino lipids containing a sulfonic acid or sulfonic acid derivative of the formulas: ##STR00001##
wherein the variables are as defined herein. These amino lipids may be used in compositions with one or more helper lipids and a nucleic acid therapeutic agent. These compositions may be used to treat a disease or disorder such as cancer, cystic fibrosis, or other genetic diseases.

Editing of VEGFR2 abrogated angiogenesis in two mouse models of oxygen-induced retinopathy (OIR) and laser-induced choroid neovascularization (CNV). Provided are compositions, e.g., Adeno-Associated Virus (AAV) Vectors comprising sequences encoding CRISPR/Cas9 proteins and guide RNA, and methods of use thereof for editing of Vascular endothelial growth factor receptor 2 (VEGFR2) gene to treat ocular disease associated with pathological angiogenesis, e.g., neovascular age-related macular degeneration (AMD), proliferative diabetic retinopathy (PDR) and retinopathy of prematurity (ROP).

The present invention relates to antisense LNA oligonucleotides (oligomers) complementary to ATXN3 pre-mRNA sequences, which are capable of inhibiting the expression of ATXN3 protein. Inhibition of ATXN3 expression is beneficial for the treatment of spinocerebellar ataxia.

Disclosed are nucleic acid nanoparticles, a pharmaceutical composition comprising the same, a drug comprising doxorubicin and a preparation method thereof. The nucleic acid nanoparticles have a nucleic acid structural domain, the nucleic acid structural domain includes a sequence a, a sequence b and a sequence c; the sequence a includes a sequence a1 or a sequence obtained by insertion, deletion or substitution of at least one base in the sequence a1, the sequence b includes a sequence b1 or a sequence obtained by insertion, deletion or substitution of at least one base in the sequence b1 and the sequence c includes a sequence d or a sequence obtained by insertion, deletion or substitution of at least one base in the sequence.

The present invention relates to a pharmaceutical composition comprising a therapeutically effective amount of (i) at least three miRNAs selected in any one of Table 1, Table 2, Table 3, Table 4, Table 5, Table 6, Table 7, Table 8, Table 9, Table 10, Table 11 or Table 12 and (ii) a pharmaceutical acceptable vehicle. The pharmaceutical composition according to the invention may be of therapeutic use for the prevention and/or the treatment of tissue disorders, including, but not limited to skin disorders, bone disorders and/or cartilage disorders.