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.

Compositions and methods for prevention of ovarian cancer recurrence and for the treatment of BRCA1/2-wild type ovarian cancer are disclosed herein. In some embodiments, the composition comprises an autologous tumor cell vaccine comprising cells genetically modified for furin knockdown and GM-CSF expression. In some embodiments, the method comprises administration of an autologous tumor cell vaccine prior to administration of a combination of the autologous tumor cell vaccine and atezolizumab. Also disclosed herein are methods for treating a cancer in an individual comprising a wild-type BRCA1 gene, a wild-type BRCA2 gene, or a combination thereof, and is identified as homologous recombination deficiency (HRD)-negative.

Described herein is the discovery that HGFs activate the growth and migration of lymphatic endothelial cells and thereby promote lymphangiogenesis. The present invention is based on this finding, and provides lymphangiogenesis-promoting agents comprising as active ingredients HGFs, or proteins or compounds functionally equivalent thereto. Based on the finding described above, the present invention also provides methods for promoting lymphangiogenesis which comprise the step of locally administering HGFs or proteins functionally equivalent thereto to affected areas in patients with lymphedema.

A method for preventing or treating cardiomyopathy due to energy failure in a subject in need thereof is provided. The method comprises administering to the subject a therapeutically effective amount of a vector which comprises a nucleic acid sequence encoding a gene that can reverse energy failure. An exemplary cardiomyopathy is that which is associated with Friedreich ataxia and an exemplary nucleic acid sequence comprises a nucleic acid that encodes frataxin (FXN).

Disclosed herein is a composition including a recombinant nucleic acid sequence that encodes an antibody. Also disclosed herein is a method of generating a synthetic antibody in a subject by administering the composition to the subject. The disclosure also provides a method of preventing and/or treating disease in a subject using said composition and method of generation.

Provided herein are methods and compositions for editing the genome of a cell. In some embodiments, a nucleotide sequence of at least 200 nucleotides in length is inserted into a target region in the genome of a cell.

A method of treating hyperglycemia, diabetes, metabolic syndrome, insulin resistance (insulin insensitivity), impaired glucose tolerance, high glucose levels, pulmonary hypertension, and/or a condition arising from any of the foregoing in a patient is provided. The method comprises knocking down mARC2 or mARC1 expression in the patient, or otherwise decreasing mARC2 and mARC1 activity in the patient.

Provided are methods and compositions for delivering a nucleic acid, protein, and/or ribonucleoprotein payload to a cell. Also provided are delivery molecules that include a peptide targeting ligand conjugated to a protein or nucleic acid payload (e.g., an siRNA molecule), or conjugated to a charged polymer polypeptide domain (e.g., poly-arginine such as 9R or a poly-histidine such as 6H, and the like). The targeting ligand provides for (i) targeted binding to a cell surface protein, and (ii) engagement of a long endosomal recycling pathway. As such, when the targeting ligand engages the intended cell surface protein, the delivery molecule enters the cell (e.g., via endocytosis) but is preferentially directed away from the lysosomal degradation pathway.

Produced the gene therapy DNA vectors based on the gene therapy DNA vector VTvaf17 for the treatment of diseases featuring disruption of mucociliary transport, mucolytic function and development of mucostasis. The gene therapy DNA vector contains the coding region of the SKI, TGFB3, TIMP2 or FMOD therapeutic genes. Methods of producing or use a gene therapy DNA vector based on gene therapy DNA vector VTvaf17 carrying SKI, TGFB3, TIMP2 or FMOD therapeutic genes. The methods of producing strain for production of gene therapy DNA vector for treatment of diseases featuring disruption of mucociliary transport and development of mucostasis. Escherichia coli strain SCS 110-AF/VTvaf17-SKI, SCS 110-AF/VTvaf17-TGFB3, SCS110-AF/VTvaf17-TIMP2 or SCS110-AF/VTvaf17-FMOD obtains by the method described above carrying gene therapy DNA vector VTvaf17-SKI, VTvaf17-TGFB3, VTvaf17-TIMP2 or VTvaf17-FMOD. The method of producing a gene therapy DNA vector carrying SKI, TGFB3, TIMP2 or FMOD therapeutic gene uses on an industrial scale.

Provided herein are variant adeno-associated virus (AAV) capsid proteins having one or more modifications in amino acid sequence relative to a parental AAV capsid protein, which, when present in an AAV virion, confer increased infectivity of one or more types of retinal cells as compared to the infectivity of the retinal cells by an AAV virion comprising the unmodified parental AAV capsid protein. Also provided are recombinant AAV virions and pharmaceutical compositions thereof comprising a variant AAV capsid protein as described herein, methods of making these rAAV capsid proteins and virions, and methods for using these rAAV capsid proteins and virions in research and in clinical practice, for example in, e.g., the delivery of nucleic acid sequences to one or more cells of the retina for the treatment of retinal disorders and diseases.