Aspects herein relate to systems and methods for delivery of biologic agents to the central nervous system. In various embodiments, a method of administering a therapeutic agent to the central nervous system (CNS) is included. The method can include injecting a therapeutic agent into a first cerebrospinal fluid (CSF) region of the subject. The method can further include establishing fluid communication between a fluid reservoir and a second cerebrospinal fluid (CSF) region of a subject, the fluid having a hydraulic pressure at or above an intracranial pressure. The method can further include infusing a hyperosmotic fluid systemically. Other embodiments, including kits and systems are also included herein.

The present disclosure relates to methods and compounds for promoting anabolic pathways in neuronal cells leading to improved neuronal survival. In particular, the present disclosure relates to inhibiting PHD to promote glycolysis and neuronal survival in a variety of neurodegenerative conditions such as retinitis pigmentosa.

The present disclosure relates to methods and compounds for promoting anabolic pathways in neuronal cells leading to improved neuronal survival. In particular, the present disclosure relates to inhibiting PHD to promote glycolysis and neuronal survival in a variety of neurodegenerative conditions such as retinitis pigmentosa.

An aptamer, capable of inhibiting DNA methyltransferase 1 (DNMT1) for use in therapy of diseases characterised by aberrant DNA methylation, e.g. cancer. Method for identifying inhibitors of DNA methyltransferase. An aptamer, capable of inhibiting DNA methyltransferase 1 (DNMT1) for use in therapy of diseases characterised by aberrant DNA methylation, e.g. cancer. SELEX method for identifying aptamers of DNA methyltransferase optionally using 2-fluoro-pyrimindine nucleotide derivatives.

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.

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.

Disclosed here are phage compositions comprising Type I CRISPR-Cas systems and methods of use thereof. In some embodiments, disclosed herein is a nucleic acid sequence comprising (a) a first CRISPR array designed to be operable with a first Type I CRISPR-Cas system, and (b) a second CRISPR array designed to be operable with a second Type I CRISPR-Cas system, wherein the first Type I CRISPR-Cas system and the second Type I CRISPR-Cas system are different Type I CRISPR-Cas systems.

Particles offering multiple doses of an active agent to a subject via a single administration of the active agent to the subject are provided. The particles comprise multiple layers, including two dosing layers each having the active agent and an intervening layer that separates the two dosing layers, and provide a first dose of the active agent from the dosing layer covering the intervening layer upon exposure to an aqueous environment after the particles are administered to the subject, and later a second dose of the active agent from the dosing layer covered by the intervening layer after the intervening layer degrades in the body of the subject. Methods for preparing the particles are also provided. Methods for treating or preventing a disease or disorder in a subject in need thereof with two or more doses of an active agent via a single administration to the subject are further provided.

Particles offering multiple doses of an active agent to a subject via a single administration of the active agent to the subject are provided. The particles comprise multiple layers, including two dosing layers each having the active agent and an intervening layer that separates the two dosing layers, and provide a first dose of the active agent from the dosing layer covering the intervening layer upon exposure to an aqueous environment after the particles are administered to the subject, and later a second dose of the active agent from the dosing layer covered by the intervening layer after the intervening layer degrades in the body of the subject. Methods for preparing the particles are also provided. Methods for treating or preventing a disease or disorder in a subject in need thereof with two or more doses of an active agent via a single administration to the subject are further provided.

The present disclosure pertains to the recognition that immune responses mediated by CpG oligonucleotides can be affected by the stereochemistry of modified internucleotidic linkages such as phosphorothioates. In some embodiments, the present disclosure relates to chirally controlled CpG oligonucleotide compositions comprising CpG oligonucleotides comprising multiple modified internucleotidic linkages such as phosphorothioate linkages, wherein the oligonucleotides comprise one or more CpG region motifs having defined stereochemistry patterns of chiral internucleotidic linkages. In some embodiments, CpG oligonucleotides comprising one or more CpG region motifs are capable of agonizing an immune response. In some embodiments, CpG oligonucleotides comprising one or more CpG region motifs are antagonistic. Methods for making and using chirally controlled CpG oligonucleotide compositions are also described. In some embodiments, no immune modulation is desired, and the present disclosure provides methods of identifying chirally controlled oligonucleotide compositions which have decreased immune modulation.