Delivery devices, systems, and methods related thereto may be used in humans for spinal delivery of cells, drugs or vectors. Thus, the system enables subpial delivery, which leads to a near complete spinal parenchymal AAV9-mediated gene expression or ASO distribution in both white and grey matter.

The invention provides a platform and methods of using the platform for the regulation of the expression of a target gene using exposure to an aptamer ligand (for example, a small molecule). The platform features a polynucleotide gene regulation cassette that is placed in the target gene and includes a synthetic riboswitch positioned in the context of a 5′ intron-alternative exon-3′ intron. The riboswitch comprises an effector region and a sensor region (e.g., an aptamer that binds a small molecule ligand) such that the alternative exon is spliced into the target gene mRNA when the ligand is not present thereby preventing expression of the target gene. When the ligand is present, the alternative exon is not spliced into the target gene mRNA thereby providing expression of the target gene.

The present disclosure provides uses of genetically engineered attenuated Salmonella typhimurium strain VNP20009-M in preventing and treating cancer metastasis. The genetically engineered strain VNP20009-M is targeted to cancer cells and has a significant effect of inhibiting metastasis and growth. VNP20009-M can be used to prepare medicaments for the prevention and treatment of tumor metastasis.

The disclosure relates to tropical diseases such as viral mosquito borne illnesses and the treatment thereof. The invention includes ribonucleic acid vaccines and combination vaccines, as well as methods of using the vaccines and compositions comprising the vaccines for treating and preventing tropical disease.

The present invention provides, among other things, methods of treating ornithine transcarbamylase (OTC) deficiency, including administering to a subject in need of treatment a composition comprising an mRNA encoding an ornithine transcarbamylase (OTC) protein at an effective dose and an administration interval such that at least one symptom or feature of the OTC deficiency is reduced in intensity, severity, or frequency or has delayed onset. In some embodiments, the mRNA is encapsulated in a liposome comprising one or more cationic lipids, one or more non-cationic lipids, one or more cholesterol-based lipids and one or more PEG-modified lipids.

Provided herein are micellic assemblies comprising a plurality of copolymers. In certain instauces, micellic assemblies provided herein are pH sensitive particles.

This invention provides formulations for use in distributing RNAi molecules targeted to a human GST-π for treating a malignant tumor in a subject. The formulation can include nanoparticles composed of an ionizable lipid, a DSPE lipid, and additional lipids. A drug product can be made by lyophilization of the formulation. This invention further provides methods for ameliorating or treating a malignant tumor by administering a therapeutically effective amount of a formulation containing the RNAi agents.

The present invention provides nucleic acid constructs, expression vectors, transgenic cell and methods of making and using the same, wherein the nucleic acid construct includes a synthetic promoter designed from the endogenous promoter of BIRC5 and LAMC2. In illustrative working embodiments of the invention, an exogenous nucleic acid fragment encoding thymidine kinase is operably linked to the synthetic promoter which is then shown to regulate the expression of this polypeptide.

The invention relates to compositions and methods for the preparation, manufacture and therapeutic use of signal-sensor polynucleotides, primary transcripts and mmRNA molecules.

The present invention provides a therapy for treating neuropathic pain by subpial administration of small quantities of a composition for spinal segment-specific upregulation of GAD65 (glutamatedecarboxylase) gene and VGAT (vesicular GABA transporter) gene, which is effective for induction of nociceptive effects by potentiating release of vesicular GABA from infected dorsal horn neurons into the synaptic cleft.