Abstract: The present disclosure provides messenger RNAs (mRNAs) having chemical and/or structural modifications, including RNA elements and/or modified nucleotides, which provide a desired translational regulatory activity to the mRNA.

Abstract: The present disclosure provides messenger RNAs (mRNAs) having chemical and/or structural modifications, including RNA elements and/or modified nucleotides, which provide desirable regulation of mRNA localization, stability, and/or translation to yield increased mRNA expression and activity of an encoded polypeptide.

Abstract: The present disclosure provides messenger RNAs (mRNAs) having chemical and/or structural modifications, including RNA elements and/or modified nucleotides, which provide a desired translational regulatory activity to the mRNA.

Abstract: The present disclosure provides messenger RNAs (mRNAs) with alterations which provide increased endonuclease resistance to the mRNA and methods and uses thereof.

Abstract: The present disclosure provides messenger RNAs (mRNAs) having chemical and/or structural modifications, including RNA elements and/or modified nucleotides, in particular C-rich or CG-rich elements, which provide a desired translational regulatory activity to the mRNA.

Abstract: The present disclosure provides messenger RNAs (mRNAs) having chemical and/or structural modifications, including RNA elements and/or modified nucleotides, which provide a desired translational regulatory activity to the mRNA.

Abstract: The present invention generally relates to various nucleases and uses thereof, and in some cases, to the UPF0054 protein superfamily. Members of the UPF0054 protein superfamily, such as the E. coli protein YbeY, may possess RNase activity and may be involved in certain important cellular processes. Disruption of YbeY activity can lead to increased sensitivity to antibiotics. Accordingly, certain embodiments of the invention are directed to systems and methods for screening target compounds for activity against UPF0054 superfamily proteins. In some embodiments, the screening method allows to target compositions to be determined that show selective activity against UPF0054 superfamily proteins. Other embodiments of the invention provide for nucleases capable of site-specific cleavage of nucleic acids.

Abstract: The present invention provides novel orthogonal suppressor tRNAs, aminoacyl-tRNA synthetases, and suppressor tRNA/aminoacyl-tRNA synthetase pairs. In preferred embodiments the suppressor tRNAs function in mammalian cells and in certain embodiments they are not aminoacylated by any of the mammalian cytoplasmic aminoacyl-tRNA synthetases. The invention provides a novel ochre suppressor tRNA that fulfills these criteria. The invention further provides novel amber and opal suppressor tRNAs having a range of different translation efficiencies. The invention also provides mammalian cells containing the suppressor tRNAs, aminoacyl-tRNA synthetases, or both. The suppressor tRNAs may be introduced into the cell from the exterior or may be expressed by the cell. They may be aminoacylated with either a natural or an unnatural amino acid. The suppressor tRNAs, aminoacyl-tRNA synthetases, or both, may be expressed by a mammalian cell in a regulated manner.

Abstract: The present invention provides techniques and reagents for read-through of stop codons in mammalian cells. In certain embodiments, the invention provides methods in which a mammalian cell is contacted with a synthesized tRNA so that the tRNA is taken up into the cell at levels that allow read-through of stop codons. Preferably, the synthesized suppressor tRNA is aminoacylated, optionally with an unnatural amino acid. In certain preferred embodiments, the inventive system is utilized to generate proteins containing two or more unnatural amino acids.

Abstract: The present invention provides techniques and reagents for read-through of stop codons in mammalian cells. In certain embodiments, the invention provides methods in which a mammalian cell is contacted with a synthesized tRNA so that the tRNA is taken up into the cell at levels that allow read-through of stop codons. Preferably, the synthesized suppressor tRNA is aminoacylated, optionally with an unnatural amino acid. In certain preferred embodiments, the inventive system is utilized to generate proteins containing two or more unnatural amino acids.