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.

The invention provides a method for generating an oligonucleotide with which an exon may be skipped in a pre-mRNA and thus excluded from a produced mRNA thereof. Further provided are methods for altering the secondary structure or an mRNA to interfere with splicing processes and uses of the oligonucleotides and methods in the treatment of disease. Further provided are pharmaceutical compositions and methods and means for inducing skipping of several exons in a pre-mRNA.

In some aspects, the disclosure relates to methods and compositions for modulation of miR-122 expression in a cell or a subject. In some embodiments, methods and compositions described by the disclosure are useful for the treatment of liver-associated diseases (e.g., chronic liver disease, alcoholic liver disease).

The present invention provides a method for assessing the risk of cancer in a subject by detecting elevated methylation level in the genomic sequence of the TET1 gene, which leads to suppressed expression of this gene. A kit and device useful for practicing such a method are also provided.

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.

Methods of treating or ameliorating inflammatory disorders and fibrosis are described. The methods include administering a therapeutically effective amount of an oligonucleotide inhibitor of TLR9 to an individual suffering from an inflammatory disorder or fibrosis. Also described are kits for treating or ameliorating inflammatory disorders and fibrosis.

The present invention relates to peptides and compositions for use in improving transduction efficiency of viruses into target cells.

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 AA V 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.

Methods and compositions are provided for activating transcription in a mammalian cell.

In various aspects and embodiments the invention provides a method of treating epilepsy in a subject in need thereof the method comprising contacting a target cell of the subject with an effective amount of an HCN4 disrupting agent.