Abstract: The present application describes a coding nucleic acid sequence, particularly a messenger RNA (mRNA), comprising or coding for a histone stem-loop and a poly(A) sequence or a polyadenylation signal and the use thereof for increasing the expression of an encoded protein. It also discloses its use for the preparation of a pharmaceutical composition, especially a vaccine e.g. for the use in the treatment of tumours and cancer diseases, cardiovascular diseases, infectious diseases, autoimmune diseases or genetic diseases, or in gene therapy. The present invention further describes an in vitro transcription method, in vitro methods for increasing the expression of a protein using the nucleic acid comprising or coding for a histone stem-loop and a poly(A) sequence or a polyadenylation signal and an ex vivo and in vivo method.

Abstract: The present invention provides a method of reducing the immunostimulatory properties of an in vitro transcribed RNA by producing the in vitro transcribed RNA comprising a 3? terminal A nucleotide. Hereby, the circular DNA template used to generate the in vitro transcribed RNA has been linearized using a type IIS endonuclease. The invention further provides pharmaceutical compositions comprising the vitro transcribed RNA comprising a 3? terminal A nucleotide according to the invention for use in therapy.

Abstract: The present invention provides optimized nucleic acid molecules, methods for optimization of nucleic acid molecules and uses of optimized nucleic acid molecules. A modular design principle is provided that is suitable to generate a nucleic acid, particularly mRNA, which is tailored for a respective application. The nucleic acid molecules of the present invention can be obtained by the versatile combination of multiple modules on nucleic acid level. Such nucleic acid, e.g. mRNA, can be tailored by combining one or more modules, comprising (i) a nucleic acid moiety encoding a polypeptide of interest (e.g. a protein potentially producing a therapeutic outcome) and (ii) at least one further coding or non-coding nucleic acid moiety, e.g.

Abstract: The invention relates to an artificial nucleic acid molecule comprising an open reading frame and a 3?-UTR comprising at least one poly(A) sequence or a polyadenylation signal. The invention further relates to a vector comprising the artificial nucleic acid molecule comprising an open reading frame and a 3?-UTR comprising at least one poly(A) sequence or a polyadenylation signal, to a cell comprising the artificial nucleic acid molecule or the vector, to a pharmaceutical composition comprising the artificial nucleic acid molecule or the vector and to a kit comprising the artificial nucleic acid molecule, the vector and/or the pharmaceutical composition. The invention also relates to a method for increasing protein production from an artificial nucleic acid molecule and to the use of a 3?-UTR for a method for increasing protein production from an artificial nucleic acid molecule.

Abstract: The invention relates to an artificial nucleic acid molecule or a vector comprising an open reading frame and a 3?-UTR comprising at least two poly(A) sequences. The invention also relates to a method for increasing protein production from an artificial nucleic acid molecule and to the use of a 3?-UTR for a method for increasing protein production from an artificial nucleic acid molecule. Moreover, the invention concerns the use of the artificial nucleic acid molecule, the vector, the kit or the pharmaceutical composition as a medicament, as a vaccine or in gene therapy.

Abstract: The present invention relates to an immobilized capping enzyme, preferably an immobilized Vaccinia virus capping enzyme. Furthermore, the present invention relates to an immobilized cap-specific nucleoside 2?-O-methyltransferase, preferably an immobilized Vaccinia virus cap-specific nucleoside 2?-O-methyltransferase. Moreover, the present invention relates to a method for immobilizing said enzymes and to a method of using said enzymes for the addition of a 5?-cap structure to RNAs. Moreover, the present invention relates to an enzyme reactor for performing the capping reaction using said immobilized enzymes and the subsequent separation of the 5?-capped RNA product. In addition, the present invention relates to a kit comprising the capping enzyme and/or the cap-specific nucleoside 2?-O-methyltransferase.

Abstract: The present invention relates to an immobilized capping enzyme, preferably an immobilized Vaccinia virus capping enzyme. Furthermore, the present invention relates to an immobilized cap-specific nucleoside 2?-O-methyltransferase, preferably an immobilized Vaccinia virus cap-specific nucleoside 2?-O-methyltransferase. Moreover, the present invention relates to a method for immobilizing said enzymes and to a method of using said enzymes for the addition of a 5?-cap structure to RNAs. Moreover, the present invention relates to an enzyme reactor for performing the capping reaction using said immobilized enzymes and the subsequent separation of the 5?-capped RNA product. In addition, the present invention relates to a kit comprising the capping enzyme and/or the cap-specific nucleoside 2?-O-methyltransferase.

Abstract: The invention relates to an artificial nucleic acid molecule comprising an open reading frame and a 3?-UTR comprising at least one poly(A) sequence or a polyadenylation signal. The invention further relates to a vector comprising the artificial nucleic acid molecule comprising an open reading frame and a 3?-UTR comprising at least one poly(A) sequence or a polyadenylation signal, to a cell comprising the artificial nucleic acid molecule or the vector, to a pharmaceutical composition comprising the artificial nucleic acid molecule or the vector and to a kit comprising the artificial nucleic acid molecule, the vector and/or the pharmaceutical composition. The invention also relates to a method for increasing protein production from an artificial nucleic acid molecule and to the use of a 3?-UTR for a method for increasing protein production from an artificial nucleic acid molecule.

Abstract: The invention relates inter alia to a combination comprising (i) a first component comprising at least one therapeutic RNA and (ii) a second component comprising at least one antagonist of at least one RNA sensing pattern recognition receptor. Further provided are compositions comprising at least one therapeutic RNA and at least one antagonist of at least one RNA sensing pattern recognition receptor. The combination of the two components is able to reduce immunostimulatory properties of the first component as well as promote expression after administration. Additionally, first and second medical uses, and methods of treating or preventing diseases, disorders or conditions are provided.

Abstract: The present invention provides artificial nucleic acid molecules comprising novel combinations of 5? and 3? untranslated region (UTR) elements. The inventive nucleic acid molecules are preferably characterized by increased expression efficacies of coding regions operably linked to said UTR elements. The artificial nucleic acids can be used for treatment or prophylaxis of various diseases. The invention further provides (pharmaceutical) compositions, vaccines and kits comprising said artificial nucleic acid molecules. Further, in vitro methods for preparing artificial nucleic acid molecules according to the invention are provided.

Abstract: The invention relates to an artificial nucleic acid molecule comprising an open reading frame and a 3?-UTR comprising at least one poly(A) sequence or a polyadenylation signal. The invention also relates to a method for increasing protein production from an artificial nucleic acid molecule and to the use of a 3?-UTR for a method for increasing protein production from an artificial nucleic acid molecule. Moreover, the invention concerns the use of the artificial nucleic acid molecule as a medicament, as a vaccine or in gene therapy.

Abstract: The invention relates to an artificial nucleic acid molecule comprising at least one open reading frame and at least one 3?-untranslated region element (3?-UTR) element comprising a nucleic acid sequence which is derived from the 3?-UTR of a ribosomal protein gene. The invention further relates to the use of such an artificial nucleic acid molecule in gene therapy and/or genetic vaccination. Furthermore, the invention relates to the use of a 3?-UTR element comprising a nucleic acid sequence which is derived from the 3?-UTR of a ribosomal protein gene for enhancing, stabilizing and/or prolonging protein expression from a nucleic acid sequence comprising such 3?-UTR element.

Abstract: The invention relates to an artificial nucleic acid molecule comprising an open reading frame and a 3?-UTR comprising at least one poly(A) sequence or a polyadenylation signal. The invention further relates to a vector comprising the artificial nucleic acid molecule comprising an open reading frame and a 3?-UTR comprising at least one poly(A) sequence or a polyadenylation signal, to a cell comprising the artificial nucleic acid molecule or the vector, to a pharmaceutical composition comprising the artificial nucleic acid molecule or the vector and to a kit comprising the artificial nucleic acid molecule, the vector and/or the pharmaceutical composition. The invention also relates to a method for increasing protein production from an artificial nucleic acid molecule and to the use of a 3?-UTR for a method for increasing protein production from an artificial nucleic acid molecule.

Abstract: The invention relates to an artificial nucleic acid molecule comprising an open reading frame and a 3?-UTR comprising at least one poly(A) sequence or a polyadenylation signal. The invention further relates to a vector comprising the artificial nucleic acid molecule comprising an open reading frame and a 3?-UTR comprising at least one poly(A) sequence or a polyadenylation signal, to a cell comprising the artificial nucleic acid molecule or the vector, to a pharmaceutical composition comprising the artificial nucleic acid molecule or the vector and to a kit comprising the artificial nucleic acid molecule, the vector and/or the pharmaceutical composition. The invention also relates to a method for increasing protein production from an artificial nucleic acid molecule and to the use of a 3?-UTR for a method for increasing protein production from an artificial nucleic acid molecule.

Abstract: The invention relates to an artificial nucleic acid molecule comprising at least one open reading frame and at least one 3?-untranslated region element (3?-UTR) element comprising a nucleic acid sequence which is derived from the 3?-UTR of a ribosomal protein gene. The invention further relates to the use of such an artificial nucleic acid molecule in gene therapy and/or genetic vaccination. Furthermore, the invention relates to the use of a 3?-UTR element comprising a nucleic acid sequence which is derived from the 3?-UTR of a ribosomal protein gene for enhancing, stabilizing and/or prolonging protein expression from a nucleic acid sequence comprising such 3?-UTR element.

Abstract: The invention relates to an artificial nucleic acid molecule comprising an open reading frame and a 3?-UTR comprising at least one poly(A) sequence or a polyadenylation signal. The invention further relates to a vector comprising the artificial nucleic acid molecule comprising an open reading frame and a 3?-UTR comprising at least one poly(A) sequence or a polyadenylation signal, to a cell comprising the artificial nucleic acid molecule or the vector, to a pharmaceutical composition comprising the artificial nucleic acid molecule or the vector and to a kit comprising the artificial nucleic acid molecule, the vector and/or the pharmaceutical composition. The invention also relates to a method for increasing protein production from an artificial nucleic acid molecule and to the use of a 3?-UTR for a method for increasing protein production from an artificial nucleic acid molecule.

Abstract: The present invention relates to a nucleic acid sequence, comprising or coding for a coding region, encoding at least one peptide or protein comprising a tumour antigen or a fragment, variant or derivative thereof, at least one histone stem-loop and a poly(A) sequence or a polyadenylation signal. Furthermore the present invention provides the use of the nucleic acid for increasing the expression of said encoded peptide or protein. It also discloses its use for the preparation of a pharmaceutical composition, especially a vaccine, e.g. for use in the treatment of cancer or tumour diseases. The present invention further describes a method for increasing the expression of a peptide or protein comprising a tumour antigen or a fragment, variant or derivative thereof, using the nucleic acid comprising or coding for a histone stem-loop and a poly(A) sequence or a polyadenylation signal.

Abstract: The invention relates to an artificial nucleic acid molecule comprising an open reading frame and a 3?-UTR comprising at least one poly(A) sequence or a polyadenylation signal. The invention further relates to a vector comprising the artificial nucleic acid molecule comprising an open reading frame and a 3?-UTR comprising at least one poly(A) sequence or a polyadenylation signal, to a cell comprising the artificial nucleic acid molecule or the vector, to a pharmaceutical composition comprising the artificial nucleic acid molecule or the vector and to a kit comprising the artificial nucleic acid molecule, the vector and/or the pharmaceutical composition. The invention also relates to a method for increasing protein production from an artificial nucleic acid molecule and to the use of a 3?-UTR for a method for increasing protein production from an artificial nucleic acid molecule.

Abstract: The present invention relates to a nucleic acid sequence, comprising or coding for a coding region, encoding at least one peptide or protein comprising a tumour antigen or a fragment, variant or derivative thereof, at least one histone stem-loop and a poly(A) sequence or a polyadenylation signal. Furthermore the present invention provides the use of the nucleic acid for increasing the expression of said encoded peptide or protein. It also discloses its use for the preparation of a pharmaceutical composition, especially a vaccine, e.g. for use in the treatment of cancer or tumour diseases. The present invention further describes a method for increasing the expression of a peptide or protein comprising a tumour antigen or a fragment, variant or derivative thereof, using the nucleic acid comprising or coding for a histone stem-loop and a poly(A) sequence or a polyadenylation signal.

Abstract: The present invention provides a method for providing modified mRNAs of reduced immunogenicity and/or immunostimulatory capacity for use in protein replacement therapy. The invention further provides modified mRNAs and pharmaceutical compositions comprising the modified mRNAs according to the invention for use in protein replacement therapy.