This invention provides RNA, oligoribonucleotide, and polyribonucleotide molecules comprising pseudouridine or a modified nucleoside, gene therapy vectors comprising same, methods of synthesizing same, and methods for gene replacement, gene therapy, gene transcription silencing, and the delivery of therapeutic proteins to tissue in vivo, comprising the molecules. The present invention also provides methods of reducing the immunogenicity of RNA, oligoribonucleotide, and polyribonucleotide molecules.

The present disclosure relates to methods, kits, and compositions for improving the efficiency of homologous recombination. In particular, the disclosure relates to methods for cloning DNA molecules directly into a genome with the combined use of promoter trapping and short homology arms, nuclear localization signal, and/or binding one or more DNA binding agents (TAL effector domain or truncated guide RNA bound by Cas9) to specific sites thereby displacing or restructuring chromatin at the target locus, and/or it increasing the accessibility of the target locus to further enzymatic modifications. The methods and compositions provided herein are, inter alia, useful for genome editing and enhancing enzymatic processes involved therein.

This invention provides RNA, oligoribonucleotide, and polyribonucleotide molecules comprising pseudouridine or a modified nucleoside, gene therapy vectors comprising same, methods of synthesizing same, and methods for gene replacement, gene therapy, gene transcription silencing, and the delivery of therapeutic proteins to tissue in vivo, comprising the molecules. The present invention also provides methods of reducing the immunogenicity of RNA, oligoribonucleotide, and polyribonucleotide molecules.

Compositions and methods are provided for improved wound healing. In particular, provided herein are compositions and methods for the direct delivery of Sirtuin-1 (Sirt1) or vectors encoding Sirt1 to the wounds (e.g., of diabetic patients). In some embodiments, provided herein are therapeutic devices comprising: (a) a vector encoding Sirtuin-1 (Sirt 1); and (b) a hydrogel carrier. In some embodiments, the vector comprises a viral vector comprising a polynucleotide sequence encoding Sirt 1. In some embodiments, the vector comprises a non-viral vector comprising a polynucleotide sequence encoding Sirt1.

The present invention solves the problem of providing more efficient barrier insulators to avoid vector silencing and to increase expression in the setting of gene transfer vectors, more particularly in the setting of gene transfer retroviral vectors. In this sense, the authors of the present invention have developed an improved insulator element, namely element IS2, which comprises the following combination of nucleic acid molecules, namely nucleic acid molecule HS4-650 bp as shown in SEQ ID No 2 and a synthetic S/MAR nucleic acid molecule containing 5 M/SARs recognition signatures (MRS) as shown in SEQ ID no 1.

This invention provides RNA, oligoribonucleotide, and polyribonucleotide molecules comprising pseudouridine or a modified nucleoside, gene therapy vectors comprising same, methods of synthesizing same, and methods for gene replacement, gene therapy, gene transcription silencing, and the delivery of therapeutic proteins to tissue in vivo, comprising the molecules. The present invention also provides methods of reducing the immunogenicity of RNA, oligoribonucleotide, and polyribonucleotide molecules.

The present invention discloses a gene delivery system containing a reduction-sensitive shielding system having a targeting function, a preparation method and an application in the field of gene therapy thereof. The gene delivery system is composed of a reduction-sensitive shielding system having a targeting function, cationic polymer material and plasmid DNA; the cationic polymer material and the plasmid DNA complexed to form complex particles, the reduction-sensitive shielding system having a targeting function is shielded on the complex surface by means of electrostatic interaction, so as to reduce the toxicity of the delivery system and successfully transfer the loaded genetic material into cells, thereby achieving expression of genetic material and completing the transfection process, and moreover, improving the targeting and the efficiency of gene transfection.

This invention provides RNA, oligoribonucleotide, and polyribonucleotide molecules comprising pseudouridine or a modified nucleoside, gene therapy vectors comprising same, methods of synthesizing same, and methods for gene replacement, gene therapy, gene transcription silencing, and the delivery of therapeutic proteins to tissue in vivo, comprising the molecules. The present invention also provides methods of reducing the immunogenicity of RNA, oligoribonucleotide, and polyribonucleotide molecules.

The present application is directed, in general, to tolerizing immune mediated particles comprising gene therapy vector antigens for use in combination with gene therapy regimens in order to reduce immunogenicity to the gene therapy vector antigens and/or transgene protein products expressed by the vectors.

The present disclosure relates to methods, kits, and compositions for improving the efficiency of homologous recombination. In particular, the disclosure relates to methods for cloning DNA molecules directly into a genome with the combined use of promoter trapping and short homology arms, nuclear localization signal, and/or binding one or more DNA binding agents (TAL effector domain or truncated guide RNA bound by Cas9) to specific sites thereby displacing or restructuring chromatin at the target locus, and/or it increasing the accessibility of the target locus to further enzymatic modifications. The methods and compositions provided herein are, inter alia, useful for genome editing and enhancing enzymatic processes involved therein.