This invention relates generally to methods of dosing pharmaceutical compositions and preparations of circular polyribonucleotides thereof.

Provided herein are methods, systems, and related vectors and compositions allowing for noninvasive control of neural circuits. In particular, the methods and systems herein described utilize acoustically targeted chemogenetics to achieve a noninvasive neuromodulation in specifically selected cell-types among spatially selected brain regions.

RNA encoding an immunogen is delivered to a large mammal at a dose of between 2 μg and 100 μg. Thus the invention provides a method of raising an immune response in a large mammal, comprising administering to the mammal a dose of between 2 μg and 100 μg of immunogen-encoding RNA. Similarly, RNA encoding an immunogen can be delivered to a large mammal at a dose of 3 ng/kg to 150 ng/kg. The delivered RNA can elicit an immune response in the large mammal.

The present invention generally relates to composition matters and methods useful for gene delivery and an option for therapeutic treatment of various diseases. Particularly, this disclosure relates to a plasmid vector comprising a fusion of a plurality of genes comprising a gene of a chemokine or a cytokine, a gene for a targeting polypeptide and genes for one or more polypeptide linkers. Methods of use and composition matters are within the scope of this disclosure.

The present invention relates to methods and compositions for inhibiting metastatic spread of cancer and/or inhibiting progression of pre-existing metastatic disease in a subject using L1CAM inhibition.

A “localizable” systemic gene therapy system is provided substantially increasing the transfection efficiency of the gene vectors into targeted tissue cells and substantially reducing the escape of the gene vectors from the targeted tissue volume, such as would waste the vectors, promote undesired immune reactions, and/or incur prohibitive costs for the required dose of gene-containing virus vectors. In this regard, the invention provides a means to simultaneously achieve local electroporation and gene-containing vector injection in a portion of a vascularized organ. It includes two double-balloon catheters that create contained volumes in parallel blood vessels for the introduction of vectors with reduced loss along with electrodes providing electroporation of the cells in the same location where the vectors are injected.

Provided herein are methods and related compositions or kits for administering viral transfer vectors in combination with synthetic nanocarriers comprising an immunosuppressant and an anti-IgM agent.

RNA encoding an immunogen is delivered to a large mammal at a dose of between 2 μg and 100 μg. Thus, the invention provides a method of raising an immune response in a large mammal, comprising administering to the mammal a dose of between 2 μg and 100 μg of immunogen-encoding RNA. Similarly, RNA encoding an immunogen can be delivered to a large mammal at a dose of 3 ng/kg to 150 ng/kg. The delivered RNA can elicit an immune response in the large mammal.

The present disclosure provides, among other things, immune suppression regimens for in vivo gene therapy and uses thereof. In various embodiments of the present disclosure, in vivo gene therapy includes delivery of at least one exogenous coding nucleic acid sequence to a stem cell of the subject. Success of in vivo gene therapy can be inhibited or reduced by immunotoxicity. The present disclosure provides compositions and methods, including among other things immune suppression regimens, that reduce immunotoxicity of in vivo gene therapy, e.g., in vivo gene therapy including administration of a viral gene therapy vector to a subject.

The present invention relates to methods and compositions for inhibiting metastatic spread of cancer and/or inhibiting progression of pre-existing metastatic disease in a subject using L1CAM inhibition.