An expression vector containing appropriate mitochondrion-targeting sequences (MTS) and appropriate 3′UTR sequences provides efficient and stable delivery of a mRNA encoding a protein (CDS) to the mitochondrion of a mammalian cell. The MTS and 3′UTR sequences guide the CDS mRNA from the nuclear compartment of the cell to mitochondrion-bound polysomes, where the CDS is translated. This provides an efficient translocation of a mature functional protein into the mitochondria. A method of targeting mRNA expressed in the nuclear compartment of a mammalian cell to the mitochondrion is also provided. The vector and methods can be used to treat defects in mitochondrial function.

Methods for in vivo administration of the coding sequence of the sirt6 gene. In particular, methods that include the administration of adeno-associated virus vectors or recombinant adeno-associated virus vectors including the coding sequence of the sirt6 gene.

The invention provides polynucleotide constructs for the regulation of gene expression by aptamer-based modulation of U1 small nuclear ribonucleoprotein (snRNP)-mediated suppression of polyadenylation and methods of using the constructs to regulate gene expression in response to the presence or absence of a ligand that binds the aptamer. The polynucleotide construct contains a U1 binding site in the context of a riboswitch comprising an effector region and an aptamer such that when the aptamer binds a ligand, target gene expression occurs.

Compositions and methods for gene editing. In some embodiments, a polynucleotide encoding Cas9 is provided that can provide one or more of improved editing efficiency, reduced immunogenicity, or other benefits.

The present disclosure provides, among other aspects, codon-altered polynucleotides encoding Factor VIII variants for expression in mammalian cells. In some embodiments, the disclosure also provides mammalian gene therapy vectors and methods for treating hemophilia A.

The disclosure provides gene therapy vectors, such as adeno-associated virus (AAV), designed for treatment of an immunoglobulin- .Math. binding protein 2 (IGHMB P2)-related disorder.

The present disclosure is directed to methods of inducing rejuvenation in a population of adult glial progenitor cells, and methods of treating a subject having a myelin deficiency. The method of inducing rejuvenation in a population of adult glial progenitor cells, may comprise: administering, to the population of adult glial progenitor cells, one or more nucleic acid molecules encoding microRNAs, wherein administering suppresses the signal transducer and activator of transcription 3 (STAT3) signaling pathway; and/or administering microRNAs, wherein administering suppresses the E2F transcription factor 6 (E2F6) signaling pathway; and/or administering microRNAs, wherein administering suppresses the Myc-associated factor X (MAX) signaling pathway, wherein said one or more nucleic acid molecules are administered in an amount sufficient to induce rejuvenation in the population of adult glial progenitor cells.

The present disclosure relates to development of a eukaryotic cell expression vector satisfying optimized conditions for gene therapies and DNA vaccines. As a result of replacing the full HCMV regulatory and transcribed region including the immediate early (IE) gene intron A of the HCMV Towne strain and the same region of various HCMV strains at the pVAX1 promoter region and comparing the difference in gene expression efficiency for the different HCMV strains, the eukaryotic cell expression vector of the present disclosure could increase the expression of various genes by about 50-150% as compared to the HCMV Towne strain. Through this, pHP3 was developed as a vector exhibiting high expression in eukaryotic cells, and it can be usefully used for gene therapies or DNA vaccines.

The disclosure in some aspects relates to recombinant adeno-associated viruses having distinct tissue targeting capabilities. In some aspects, the disclosure relates to gene transfer methods using the recombinant adeno-associated viruses. In some aspects, the disclosure relates to isolated AAV capsid proteins and isolated nucleic acids encoding the same.

The present invention relates to an RNA encoding a therapeutic protein, in particular a collagenase, growth factor, cytokine, receptor, chaperone or signal transduction inhibitor. In particular, the present invention relates to RNA suitable for treatment of wounds, specifically for promoting wound healing. The present invention concerns such RNA as well as pharmaceutical compositions and kits and combinations comprising the RNA. Furthermore, the present invention relates to the RNA, pharmaceutical compositions, kits as disclosed herein for use in the treatment of wounds, specifically for promoting wound healing.