The disclosure provides methods and compositions useful for obtaining induced stem cells, methods of making and use thereof.

The present invention relates generally to synthetic genes for modifying endogenous gene expression in a cell, tissue or organ of a transgenic organism, in particular a transgenic animal or plant. More particularly, the present invention provides novel synthetic genes and genetic constructs which are capable of repressing delaying or otherwise reducing the expression of an endogenous gene or a target gene in an organism when introduced thereto.

The present invention relates generally to a method of modifying gene expression and to synthetic genes for modifying endogenous gene expression in a cell, tissue or organ of a transgenic organism, in particular a transgenic animal or plant. More particularly, the present invention utilizes recombinant DNA technology to post-transcriptionally modify or modulate the expression of a target gene in a cell, tissue organ or whole organism, thereby producing novel phenotypes. Novel synthetic genes and genetic constructs which are capable of repressing delaying or otherwise reducing the expression of an endogenous gene or target gene in an organism when introduced thereto are also provided.

The present invention concerns: a) an isolated peptide comprising an amino acid sequence which is at least 90% identical to the VP4 amino acid sequence of a rhinovirus, or an isolated polynucleotide comprising a nucleic acid sequence encoding said peptide, placed under the control of the elements necessary for its expression in a mammalian cell; and/or b) an isolated peptide comprising an amino acid sequence of at least 100 amino acids which is at least 90% identical to an amino acid sequence located in the last 363 C-terminal amino acids of the RNA polymerase of a rhinovirus, or an isolated polynucleotide comprising a nucleic acid sequence encoding said peptide, placed under the control of the elements necessary for its expression in a mammalian cell; and c) a Th1 adjuvant when said immunogenic composition comprises one or more of said isolated peptides.

The present disclosure relates to engineered RNA polymerase polypeptides and compositions thereof, as well as polynucleotides encoding the engineered RNA polymerase polypeptides. The present disclosure also provides methods of using the engineered RNA polymerase polypeptides or compositions thereof for producing RNA.

Provided herein, in some aspects, are methods and compositions for cell-free production of ribonucleic acid.

The present invention relates to polypeptide fragments comprising an amino-terminal fragment of the PA subunit of a viral RNA-dependent RNA polymerase or variants thereof possessing endonuclease activity, wherein said PA subunit is from a virus belonging to the Orthomyxoviridae family. This invention also relates to (i) crystals of the polypeptide fragments which are suitable for structure determination of said polypeptide fragments using X-ray crystallography and (ii) computational methods using the structural coordinates of said polypeptide to screen for and design compounds that modulate, preferably inhibit the endonucleolytically active site within the polypeptide fragment. In addition, this invention relates to methods identifying compounds that bind to the PA polypeptide fragments possessing endonuclease activity and preferably inhibit said endonucleolytic activity, preferably in a high throughput setting. This invention also relates to compounds and pharmaceutical compositions comprising the identified compounds for the treatment of disease conditions due to viral infections caused by viruses of the Orthomyxoviridae family.

The invention relates to constructs comprising a transmembrane protein pore subunit and a nucleic acid handling enzyme. The pore subunit is covalently attached to the enzyme such that both the subunit and enzyme retain their activity. The constructs can be used to generate transmembrane protein pores having a nucleic acid handling enzyme attached thereto. Such pores are particularly useful for sequencing nucleic acids. The enzyme handles the nucleic acid in such a way that the pore can detect its component nucleotides by stochastic sensing.

Provided herein are attenuated influenza viruses and methods of making attenuated influenza viruses.

The disclosure provides methods and compositions useful for obtaining induced stem cells, methods of making and use thereof.