NEW ARTIFICIAL NUCLEIC ACID MOLECULES.

Abstract

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

Description

[0001] Novel artificial nucleic acid molecules

[0002] To date, therapeutic nucleic acids in the form of naked DNA, viral or bacterial DNA vectors are exploited for a variety of purposes. Gene therapy seeks to treat diseases by transferring one or more therapeutic nucleic acids to a patient's cells (gene addition therapy) or by correcting a defective gene (gene replacement therapy), for example by gene editing. This technology transfer holds the promise of providing lasting therapies for diseases that are not -or only temporarily- curable with conventional treatment options, and even to provide treatments for diseases previously classified as unbeatable. Currently available gene therapy strategies are typically based on either in wVo gene delivery to postmitotic target cells or tissues or ex vivo gene delivery into autologous cells followed by adoptive transfer back into the patient (Kumar et al. Mol Ther Methods Clin Dev. 2016; 3: 16034). For some time, clinical gene therapy was characterized by some encouraging results, but also several setbacks. The preferred method of gene delivery, in terms of defined composition and manufacturing reproducibility, would involve naked DNA provided in a suitable carrier such as synthetic particles, for example, using lipids or polymers. However, these methods have not yet achieved efficient uptake and sustained gene expression in vivo. Thus, gene replacement therapy trials that have demonstrated some clinical benefit, relied on viral vectors for gene delivery. Among the various viral based vector systems, adeno-associated virus (AAV) DNA vectors are most commonly used for in vivo gene delivery. The use of retroviral vectors (γ-retroviral or lentivirus derived), which are capable of integrating into the target cells' genome, is somewhat hampered by safety and ethical issues. Concerns regarding retroviral geen therapy are based on the possible generation of replication competent retroviruses during vector production, mobilisation of the vector by endogenous retroviruses in genome, insertional mutagenesis leading to cancer, germline alteration and dissemination of new viruses from gene therapy patients. Although AAV-based vectors generally do not integrate into the patient's genome and thus avoid many of these potential risks, remaining concerns emanate from occasionally observed site-specific integration events, the shedding of vectors from treated patients and potential adverse effects caused by immune responses to viral structural proteins.

[0003] Immunotherapy is the second, important field of application for therapeutic nucleic acids. In particular, DNA vaccines encoding tumor antigens have been evaluated for cancer immunotherapy. In principle, harnessing the patient's own adaptive immunity to fight cancer cells seems appealing. DNA-based vaccines based on non-viral DNA vectors can generally be easily engineered and produced rapidly in large quantities. These DNA vectors are stable and can be easily stored and transported. Unlike live attenuated bacterial or viral vaccines, there is no risk of pathogenic infection or the induction of an anti-viral immune response. Naked DNA does not easily spread from cell to cell in vivo. APCs do not readily take up expressed antigens and activate satisfactory immune responses (Yang et al. Hum Vaccin Immunother. 2014 Nov; 10(11): 3153-3164). On the other hand, the limited uptake and consequent limited antigen-transcription by transferred cells is the major drawback of non-viral DNA-based vaccines. Indeed, anti-tumor vaccination with tumor-antigen encoding DNAs achieved some success in immunization-protection experiments, and several types of anti-cancer vaccines have been designed, manufactured, and pre-clinically tested. However, effectiveness in inducing a measurable immune response and in extending patients' overall survival has been modest in clinical trials. Administration through eiectroporation or viral-mediated delivery solves the issue but opens new problems. In the case of eiectroporation, the availability of clinically approved devices and patients' compliance have limited their use in clinic. In the case of viral-mediated delivery, the problems are mainly related to potential dangers associated with the administration of live virus together with the presence of anti-viral neutralizing antibodies in patients (Lollini et al. Vaccines. 2015 Jun; 3(2): 467-489).

[0004] Since their initial development, nucleic acid-based vaccine and gene therapy technologies have come a long way. Unfortunately, when applied to human subjects inadequate uptake and transcription only achieved limited clinical success due to insufficient gene or antigen expression. Inadequate delivery of therapeutic proteins (in case of gene therapy) or immunogenicity (in case of immunotherapy) are still the biggest challenge for practical use of therapeutic DNAs. Li and Petrovsky Expert Rev Vaccines. 2016; 15(3): 313-329. Although RNA-based therapeutics overcome many of the shortcomings of therapeutic DNAs, there is still room for improvement with regard to the expression efficacies currently observed for available therapeutic RNAs. Thus, effective strategies that help enhance therapeutic nucleic acid potency are urgently needed. It is an object of the present invention to comply with the needs set out above.

[0005] Although the present invention is described in detail below, it is to be understood that this invention is not limited to the particular methodologies, protocols and reagents described herein as these may vary. It is also to be understood that the terminology used herein is not intended to limit the scope of the present invention which will be limited only by the appended claims. Unless defined otherwise, all technical and scientific terms used herein have the same meanings as commonly understood by one of ordinary skill in the art.

[0006] In the following, the elements of the present invention will be described. These elements are listed with specific embodiments, however, it should be understood that they may be combined in any manner and in any number to create additional embodiments. The variously described examples and preferred embodiments should not be construed to limit the present invention to only the explicitly described embodiments. This description should be understood to support and encompass embodiments which combine the explicitly described embodiments with any number of the disclosed and / or preferred elements. Furthermore, any permutations and combinations of all described elements in this application should be considered disclosed by the description of the present application unless the context indicates otherwise.

[0007] Throughout this specification and the claims which follow, unless the context requires otherwise, the term "comprise", and variations such as "comprises" and "comprising", will be understood to imply the inclusion of a stated member, integer or step but not the exclusion of any other non-stated member, integer or step. The term "consist of is a particular embodiment of the term "comprise", wherein any other non-stated member, integer or step is excluded. In the context of the present invention, the term "comprise" encompasses the term "consist of. The term "comprising" thus encompasses "including" as well as "consisting" e.g., a composition "comprising" X may consist exclusively of X or may include something additional e.g., X + Y.

[0008] The terms "a" and "an" and "the" and similar reference used in the context of describing the invention (especially in the context of the claims) are to be construed to cover both the singular and the plural, unless otherwise indicated herein or clearly contradicted by context. Recitation of ranges of values herein is merely intended to serve as a shorthand method of referring individually to each separate value falling within the range. Unless otherwise indicated herein, each individual value is incorporated into the specification as if it were individually recited herein. No language in the specification should be construed as indicating any non-claimed element essential to the practice of the invention.

[0009] The word "substantially" does not exclude "completely" e.g., a composition which is "substantially free" from Y may be completely free from Y. Where necessary, the word "substantially" may be omitted from the definition of the invention.

[0010] The term "about" in relation to a numerical value x means x ± 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9% or 10%.

[0011] In the present invention, if not otherwise indicated, different features of alternatives and embodiments may be combined with each other.

[0012] For the sake of clarity and readability the following definitions are provided. Any technical feature mentioned for these definitions may be read on each and every embodiment of the invention. Additional definitions and explanations may be specifically provided in the context of these embodiments.

[0013] Definitions

[0014] Artificial nucleic acid molecule: An artificial nucleic acid molecule may typically be understood to be a nucleic acid molecule, e.g. a DNA or an NA, which does not occur naturally. In other words, an artificial nucleic acid molecule may be understood as a non-natural nucleic acid molecule. Such nucleic acid molecule may be non-natural due to its individual sequence (which does not occur naturally) and / or due to other modifications, e.g. structural modifications of nucleotides, which do not occur naturally. An artificial nucleic acid molecule may be a DNA molecule, an RNA molecule or a hybrid- molecule comprising DNA and RNA portions. Typically, artificial nucleic acid molecules may be designed and / or generated by genetic engineering methods to correspond to a desired artificial sequence of nucleotides (heterologous sequence). In this context an artificial sequence is usually a sequence that may not occur naturally, i.e. it differs from the wild type sequence by at least one nucleotide. The term "wild type" may be understood as a sequence occurring in nature. Further, the term "artificial nucleic acid molecule" is not restricted to mean "one single molecule" but is, typically, understood to comprise an ensemble of identical molecules. Accordingly, it may relate to a plurality of identical molecules contained in an aliquot.

[0015] DNA: DNA is the usual abbreviation for deoxyribonucleic acid. It is a nucleic acid molecule, i.e. a polymer consisting of nucleotides. These nucleotides are usually deoxy-adenosine-monophosphate, deoxy-thymidine-monophosphate, deoxy- guanosine-monophosphate and deoxy-cytidine-monophosphate monomers which are-by themselves-composed of a sugar moiety (deoxyribose), a base moiety and a phosphate moiety, and polymerize by a characteristic backbone structure. The backbone structure is, typically, formed by phosphodiester bonds between the sugar moiety of the nucleotide, i.e. deoxyribose, of a first and a phosphate moiety of a second, adjacent monomer. The specific order of the monomers, i.e. the order of the bases linked to the sugar / phosphate-backbone, is called the DNA sequence. DNA may be single stranded or double stranded. In the double stranded form, the nucleotides of the first strand typically hybridize with the nucleotides of the second strand, e.g. by A / T-base-pairing and G / C-base-pairing. Heterologous sequence: Two sequences are typically understood to be 'heterologous' if they are not derivable from the same gene. I.e., although heterologous sequences may be derivable from the same organism, they naturally (in nature) do not occur in the same nucleic acid molecule, such as in the same mRNA.

[0016] Cloning site: A cloning site is typically understood to be a segment of a nucleic acid molecule, which is suitable for insertion of a nucleic acid sequence, e.g., a nucleic acid sequence comprising an open reading frame. Insertion may be performed by any molecular biological method known to the one skilled in the art, e.g. by restriction and ligation. A cloning site typically comprises one or more restriction enzyme recognition sites (restriction sites). These one or more restrictions sites may be recognized by restriction enzymes which cleave the DNA at these sites. A cloning site which comprises more than one restriction site may also be termed a multiple cloning site ( CS) or a poly-linker.

[0017] Nucleic acid molecule: A nucleic acid molecule is a molecule comprising, preferably consisting of nucleic acid components. The term nucleic acid molecule preferably refers to DNA or RNA molecules. It is preferably used synonymous with the term "polynucleotide". Preferably, a nucleic acid molecule is a polymer comprising or consisting of nucleotide monomers, which are covalently linked to each other by phosphodiester-bonds of a sugar / phosphate-backbone. The term "nucleic acid molecule" also encompasses modified nucleic acid molecules, such as base-modified, sugar-modified or backbone- modified etc. DNA or RNA molecules.

[0018] Open reading frame: An open reading frame (ORF) in the context of the invention may typically be a sequence of several nucleotide triplets, which may be translated into a peptide or protein. An open reading frame preferably contains a start codon, i.e. a combination of three subsequent nucleotides coding usually for the amino acid methionine (ATG), at its 5'-end and a subsequent region, which usually exhibits a length which is a multiple of 3 nucleotides. An ORF is preferably terminated by a stop-codon (e.g., TAA, TAG, TGA). Typically, this is the only stop-codon of the open reading frame. Thus, an open reading frame in the context of the present invention is preferably a nucleotide sequence, consisting of a number of nucleotides that may be divided by three, which starts with a start codon (e.g. ATG) and which preferably terminates with a stop codon (e.g., TAA, TGA, or TAG). The open reading frame may be isolated or it may be incorporated in a longer nucleic acid sequence, for example in a vector or an mRNA. An open reading frame may also be termed "(protein) coding sequence" or, preferably, "coding sequence".

[0019] Peptide: A peptide or polypeptide is typically a polymer of amino acid monomers, linked by peptide bonds. It typically contains less than 50 monomer units. Nevertheless, the term peptide is not a disclaimer for molecules having more than 50 monomer units. Long peptides are also called polypeptides, typically having between 50 and 600 monomeric units.

[0020] Protein A protein typically comprises one or more peptides or polypeptides. A protein is typically folded into 3- dimensional form, which may be required for the protein to exert its biological function.

[0021] Restriction site: A restriction site, also termed restriction enzyme recognition site, is a nucleotide sequence recognized by a restriction enzyme. A restriction site is typically a short, preferably palindromic nucleotide sequence, e.g. a sequence comprising 4 to 8 nucleotides. A restriction site is preferably specifically recognized by a restriction enzyme. The restriction enzyme typically cleaves a nucleotide sequence comprising a restriction site at this site. In a double-stranded nucleotide sequence, such as a double-stranded DNA sequence, the restriction enzyme typically cuts both strands of the nucleotide sequence.

[0022] RNA, mRNA: RNA is the usual abbreviation for ribonucleic-acid. It is a nucleic acid molecule, i.e. a polymer consisting of nucleotides. These nucleotides are usually adenosine-monophosphate, uridine-monophosphate, guanosine- monophosphate and cytidine-monophosphate monomers which are connected to each other along a so-called backbone. The backbone is formed by phosphodiester bonds between the sugar, i.e. ribose, of a first and a phosphate moiety of a second, adjacent monomer. The specific succession of the monomers is called the RNA-sequence. Usually RNA may be obtainable by transcription of a DNA-sequence, e.g., inside a cell. In eukaryotic cells, transcription is typically performed inside the nucleus or the mitochondria. In vivo, transcription of DNA usually results in the so-called premature RNA which has to be processed into so-called messenger-RNA, usually abbreviated as mRNA. Processing of the premature RNA, e.g. in eukaryotic organisms, comprises a variety of different posttranscriptional-modifications such as splicing, 5'-capping, polyadenylation, export from the nucleus or the mitochondria and the like. The sum of these processes is also called maturation of RNA. The mature messenger RNA usually provides the nucleotide sequence that may be translated into an amino-acid sequence of a particular peptide or protein. Typically, a mature mRNA comprises a 5'-cap, a 5 -UTR, an open reading frame, a 3'-UTR and a poly(A) sequence. Aside from messenger RNA, several non-coding types of RNA exist which may be involved in regulation of transcription and / or translation.

[0023] Sequence of a nucleic acid molecule: The sequence of a nucleic acid molecule is typically understood to be the particular and individual order, i.e. the succession of its nucleotides. The sequence of a protein or peptide is typically understood to be the order, i.e. the succession of its amino acids.

[0024] Sequence identity: Two or more sequences are identical if they exhibit the same length and order of nucleotides or amino acids. The percentage of identity typically describes the extent to which two sequences are identical, i.e. it typically describes the percentage of nucleotides that correspond in their sequence position with identical nucleotides of a reference-sequence. For determination of the degree of identity ("% identity), the sequences to be compared are typically considered to exhibit the same length, i.e. the length of the longest sequence of the sequences to be compared. This means that a first sequence consisting of 8 nucleotides is 80% identical to a second sequence consisting of 10 nucleotides comprising the first sequence. In other words, in the context of the present invention, identity of sequences preferably relates to the percentage of nucleotides or amino acids of a sequence which have the same position in two or more sequences having the same length. Specifically, the "% identity" of two amino acid sequences or two nucleic acid sequences may be determined by aligning the sequences for optimal comparison purposes (e.g., gaps can be introduced in either sequences for best alignment with the other sequence) and comparing the amino acids or nucleotides at corresponding positions. Gaps are usually regarded as non-identical positions, irrespective of their actual position in an alignment. The "best alignment" is typically an alignment of two sequences that results in the highest percent identity. The percent identity is determined by the number of identical nucleotides in the sequences being compared (i.e., % identity = # of identical positions / total # of positions x 100). The determination of percent identity between two sequences can be accomplished using a mathematical algorithm known to those of skill in the art.

[0025] Stabilized nucleic acid molecule: A stabilized nucleic acid molecule is a nucleic acid molecule, preferably a DNA or RNA molecule that is modified such, that it is more stable to disintegration or degradation, e.g., by environmental factors or enzymatic digest, such as by an exo- or endonuclease degradation, than the nucleic acid molecule without the modification. Preferably, a stabilized nucleic acid molecule in the context of the present invention is stabilized in a cell, such as a prokaryotic or eukaryotic cell, preferably in a mammalian cell, such as a human cell. The stabilization effect may also be exerted outside of cells, e.g. in a buffer solution etc., for example, in a manufacturing process for a pharmaceutical composition comprising the stabilized nucleic acid molecule.

[0026] Transfection: The term "transfection" refers to the introduction of nucleic acid molecules, such as DNA or RNA (e.g. mRNA) molecules, into cells, preferably into eukaryotic cells. In the context of the present invention, the term "transfection" encompasses any method known to the skilled person for introducing nucleic acid molecules into cells, preferably into eukaryotic cells, such as into mammalian cells. Such methods encompass, for example, electroporation, lipofection, e.g. based on cationic lipids and / or liposomes, calcium phosphate precipitation, nanoparticle based transfection, virus based transfection, or transfection based on cationic polymers, such as DEAE-dextran or polyethylenimine etc. Preferably, the introduction is non-viral.

[0027] Vector: The term "vector" refers to a nucleic acid molecule, preferably to an artificial nucleic acid molecule. A vector in the context of the present invention is suitable for incorporating or harboring a desired nucleic acid sequence, such as a nucleic acid sequence comprising an open reading frame. Such vectors may be storage vectors, expression vectors, cloning vectors, transfer vectors etc. A storage vector is a vector, which allows the convenient storage of a nucleic acid molecule, for example, of an mRNA molecule. Thus, the vector may comprise a sequence corresponding, e.g., to a desired mRNA sequence or a part thereof, such as a sequence corresponding to the coding sequence and the 3'-UTR of an mRNA. An expression vector may be used for production of expression products such as RNA, e.g. mRNA, or peptides, polypeptides or proteins. For example, an expression vector may comprise sequences needed for transcription of a sequence stretch of the vector, such as a promoter sequence, e.g. an RNA polymerase promoter sequence. A cloning vector is typically a vector that contains a cloning site, which may be used to incorporate nucleic acid sequences into the vector. A cloning vector may be, e.g., a plasmid vector or a bacteriophage vector. A transfer vector may be a vector, which is suitable for transferring nucleic acid molecules into cells or organisms, for example, viral vectors. A vector in the context of the present invention may be, e.g., an RNA vector or a DNA vector. Preferably, a vector is a DNA molecule. Preferably, a vector in the sense of the present application comprises a cloning site, a selection marker, such as an antibiotic resistance factor, and a sequence suitable for multiplication of the vector, such as an origin of replication.

[0028] Vehicle: A vehicle is typically understood to be a material that is suitable for storing, transporting, and / or administering a compound, such as a pharmaceutically active compound. For example, it may be a physiologically acceptable liquid, which is suitable for storing, transporting, and / or administering a pharmaceutically active compound.

[0029] In nature, precise control of gene expression is vital to rapidly adjust to environmental stimuli that alter the physiological status of the cell, like cellular stress or infection. Gene expression programs undergo constant regulation and are tightly regulated by multi-layered regulatory elements acting in both c / sand trans. For such precise control the cellular machinery has evolved regulators at several stages from transcription to translation fine-tuning gene expression. These include structural and chemical modifications of chromosomal DNA, transcriptional regulation, post-transcriptional control of messenger RNA (mRNA), varying translational efficiency and protein turnover. These mechanisms in concert determine the spatio-temporal control of genes. Messenger RNA is composed of a protein-coding region, and 5'and 3 untranslated regions (UTRs). The 3' UTR is variable in sequence and size; it spans between the stop codon and the poly(A) tail. Importantly, the 3' UTR sequence harbours several regulatory motifs that determine mRNA turnover, stability and localization, and thus governs many aspects of post-transcriptional gene regulation (Schwerk and Savan. J Immunol. 2015 Oct 1; 195(7): 2963-2971). In gene therapy and immunotherapy applications, the tight regulation of transgene expression is of paramount importance to therapeutic safety and efficacy. Transgenes need to be expressed in optimal thresholds at the right places. However, the ability to control the level of transgene expression in order to provide a balance between therapeutic efficacy and nonspecific toxicity still remains a major challenge of present gene therapy and immunotherapy applications. The present inventors surprisingly discovered that certain combinations of 5' and 3'-untranslated regions (UTRs) act in concert to synergistically enhance the expression of operably linked nucleic acid sequences. Artificial nucleic acid molecules harbouring the inventive UTR combinations advantageously enable the rapid and transient expression of high amounts of (poly-)peptides or proteins delivered for gene therapy or immunotherapy purposes. Furthermore, the novel nucleic acid-based therapeutics disclosed herein preferably offer additional advantages over currently available treatment options, including the reduced risk of insertional mutagenesis, and a greater efficacy of non-viral delivery and uptake. Accordingly, the artificial nucleic acids provided herein are particularly useful for various therapeutic applications in vivo, including, for instance gene therapy, cancer immunotherapy or the vaccination against infective agents.

[0030] Accordingly, in a first aspect, the present invention thus relates to an artificial nucleic acid molecule comprising at least one 5' untranslated region (5' UTR) element derived from a 5' UTR of a gene selected from the group consisting of HSD17B4, ASAH1, ATP5A1, P68, NDUFA4, NOSIP, RPL31, SLC7A3, TUBB4B and UBQLN2; at least one 3' untranslated region (3' UTR) element derived from a 3' UTR of a gene selected from the group consisting of PSMB3, CASP1, COX6B1, GNAS, NDUFA1 and RPS9; and optionally at least one coding region operably linked to said 3' UTR and said 5' UTR.

[0031] The term "UTR" refers to an "untranslated region" located upstream (5') and / or downstream (3 a coding region of a nucleic acid molecule as described herein, thereby typically flanking said coding region. Accordingly, the term "UTR" generally encompasses 3'untranslated regions ("3'-UTRs") and 5'-untranslated regions ("5'-UTRs"). UTRs may typically comprise or consist of nucleic acid sequences that are not translated into protein. Typically, UTRs comprise "regulatory elements". The term "regulatory element" refers to a nucleic acid sequences having gene regulatory activity, the ability to affect the expression, in particular transcription or translation, of an operably (in as or trans) linked transcribable nucleic acid sequence. The term includes promoters, enhancers, internal ribosomal entry sites (IRES), introns, leaders, transcription termination signals, such as polyadenylation signals and poly-U sequences and other expression control elements. Regulatory elements may act constitutively or in a time- and / or cell specific manner. Optionally, regulatory elements may exert their function via interacting with (e.g. recruiting and binding) of regulatory proteins capable of modulating (inducing, enhancing, reducing, abrogating, or preventing) the expression, in particular transcription of a gene. UTRs are preferably "operably linked", i.e. placed in a functional relationship, to a coding region, preferably in a manner that allows them to control (i.e. modulate or regulate, preferably enhance) the expression of said coding sequence. A "UTR" preferably comprises or consists of a nucleic acid sequence, which is derived from the (naturally occurring, wild- type) UTR of a gene, preferably a gene as exemplified herein. The term "UTR element" as used herein typically refers to nucleic acid sequence corresponding to the shorter sub-sequence of the UTR of the parent gene ("parent" UTR). In this context, the term "corresponding to" means that the UTR element may comprise or consist of the RNA sequence transcribed from gene from which the "parent" UTR is derived (i.e. equal to the RNA sequence used for defining said "parent" UTR), or the respective DNA sequence (including sense and antisense strand, mature and immature) equivalent to said RNA sequence, or a mixture thereof. When referring to an UTR element "derived from" the UTR of a certain gene, the UTR element may be derived from any naturally occurring homolog, variant or fragment of said gene. I.e., when referring to a UTR element "derived from" a HSD17B4 gene, the respective UTR element may consist of a nucleic acid sequence corresponding to a shorter subsequence of the UTR of the "parent" HSD17B4 gene, or any HSD17B4 homolog, variant or fragment (in particular including HSD17B4 homologs, variants or fragments including variations in the UTR region as compared to the "parent" HSD17B4 gene).

[0032] The term "derived from" as used throughout the present specification in the context of an artificial nucleic acid, i.e. for an artificial nucleic acid "derived from" (another) artificial nucleic acid, also means that the (artificial) nucleic acid, which is derived from (another) artificial nucleic acid, shares e.g. at least 60%, 70%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the nucleic acid from which it is derived. The skilled person is aware that sequence identity is typically calculated for the same types of nucleic acids, i.e. for DNA sequences or for RNA sequences. Thus, it is understood, if a DNA is "derived from" an RNA or if an RNA is "derived from" a DNA, in a first step the RNA sequence is converted into the corresponding DNA sequence (in particular by replacing the uracils (U) by thymidines (T) throughout the sequence) or, vice versa, the DNA sequence is converted into the corresponding RNA sequence (in particular by replacing the T by U throughout the sequence). Thereafter, the sequence identity of the DNA sequences or the sequence identity of the RNA sequences is determined. Preferably, a nucleic acid "derived from" a nucleic acid also refers to nucleic acid, which is modified in comparison to the nucleic acid from which it is derived, e.g. in order to increase RNA stability even further and / or to prolong and / or increase protein production. In the context of amino acid sequences (e.g. antigenic peptides or proteins) the term "derived from" means that the amino acid sequence, which is derived from (another) amino acid sequence, shares e.g. at least 60%, 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequence from which it is derived.

[0033] The term "homolog" in the context of genes (or nucleic acid sequences derived therefrom or comprised by said gene, like a UTR) refers to a gene (or a nucleic acid sequences derived therefrom or comprised by said gene) related to a second gene (or such nucleic acid sequence) by descent from a common ancestral DNA sequence. The term, "homolog" includes genes separated by the event of speciation ("ortholog") and genes separated by the event of genetic duplication ("paralog").

[0034] The term "variant" in the context of nucleic acid sequences of genes refers to nucleic acid sequence variants, i.e. nucleic acid sequences or genes comprising a nucleic acid sequence that differs in at least one nucleic acid from a reference (or "parent") nucleic acid sequence of a reference (or "parent") nucleic acid or gene. Variant nucleic acids or genes may thus preferably comprise, in their nucleic acid sequence, at least one mutation, substitution, insertion or deletion as compared to their respective reference sequence. Preferably, the term "variant" as used herein includes naturally occurring variants, and engineered variants of nucleic acid sequences or genes. Therefore, a "variant" as defined herein can be derived from, isolated from, related to, based on or homologous to the reference nucleic acid sequence.„Variants" may preferably have a sequence identity of at least 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%, preferably of at least 70%, more preferably of at least 80%, even more preferably at least 85%, even more preferably of at least 90% and most preferably of at least 95% or even 97%, to a nucleic acid sequence of the respective naturally occurring (wild-type) nucleic acid sequence or gene, or a homolog, fragment or derivative thereof.

[0035] Also, the term "variant" as used throughout the present specification in the context of proteins or peptides will be recognized and understood by the person of ordinary skill in the art, and is e.g. intended to refer to a proteins or peptide variant having an amino acid sequence which differs from the original sequence in one or more mutation(s), such as one or more substituted, inserted and / or deleted amino acid(s). Preferably, these fragments and / or variants have the same biological function or specific activity compared to the full-length native protein, e.g. its specific antigenic property. "Variants" of proteins or peptides as defined herein may comprise conservative amino acid substitution(s) compared to their native, i.e. non-mutated physiological, sequence. Those amino acid sequences as well as their encoding nucleotide sequences in particular fall under the term variants as defined herein. Substitutions in which amino acids, which originate from the same class, are exchanged for one another are called conservative substitutions. In particular, these are amino acids having aliphatic side chains, positively or negatively charged side chains, aromatic groups in the side chains or amino acids, the side chains of which can enter into hydrogen bridges, e.g. side chains which have a hydroxyl function. This means that e.g. an amino acid having a polar side chain is replaced by another amino acid having a likewise polar side chain, or, e.g., an amino acid characterized by a hydrophobic side chain is substituted by another amino acid having a likewise hydrophobic side chain (e.g. serine (threonine) by threonine (serine) or leucine (isoleucine) by isoleucine (leucine)). Insertions and substitutions are possible, in particular, at those sequence positions which cause no modification to the three-dimensional structure or do not affect the binding region. Modifications to a three-dimensional structure by insertion(s) or deletion(s) can easily be determined e.g. using CD spectra (circular dichroism spectra). A "variant" of a protein or peptide may have at least 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% amino acid identity over a stretch of at least 10, 20, 30, 50, 75 or 100 amino acids of such protein or peptide. Preferably, a variant of a protein comprises a functional variant of the protein, which means that the variant exerts the same effect or functionality or at least 40%, 50%, 60%, 70%, 80%, 90%, or 95% of the effect or functionality as the protein it is derived from.

[0036] The term "fragment" in the context of nucleic acid sequences or genes refers to a continuous subsequence of the full- length reference (or "parent") nucleic acid sequence or gene. In other words, a "fragment" may typically be a shorter portion of a full-length nucleic acid sequence or gene. Accordingly, a fragment, typically, consists of a sequence that is identical to the corresponding stretch within the full-length nucleic acid sequence or gene. The term includes naturally occurring fragments as well as engineered fragments. A preferred fragment of a sequence in the context of the present invention, consists of a continuous stretch of nucleic acids corresponding to a continuous stretch of entities in the nucleic acid or gene the fragment is derived from, which represents at least 20%, preferably at least 30%, more preferably at least 40%, more preferably at least 50%, even more preferably at least 60%, even more preferably at least 70%, and most preferably at least 80% of the total (i.e. full-length) nucleic acid sequence or gene from which the fragment is derived. A sequence identity indicated with respect to such a fragment preferably refers to the entire nucleic acid sequence or gene. Preferably, a "fragment" may comprise a nucleic acid sequence having a sequence identity of at least 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%, preferably of at least 70%, more preferably of at least 80%, even more preferably at least 85%, even more preferably of at least 90% and most preferably of at least 95% or even 97%, to a reference nucleic acid sequence or gene that it is derived from.

[0037] UTR elements are preferably "functional", i.e. capable of eliciting the same desired biological effect as the parent UTRs that they are derived from, i.e. in particular of modulating, controlling or regulating (inducing, enhancing, reducing, abrogating, or preventing, preferably inducing or enhancing) the expression of an operably linked coding sequence. The term "expression" as used herein generally includes all step of protein biosynthesis, inter alia transcription, mRNA processing and translation. UTR elements, in particular 3'-UTR elements and 5'UTR elements in the combinations specified herein, may for instance (typically via the action of regulatory regions comprised by said UTR elements) regulate polyadenylation, translation initiation, translation efficiency, localization, and / or stability of the nucleic acid comprising said UTR elements.

[0038] Artificial nucleic acid molecules of the invention advantageously comprise at least one 5' UTR element and at least one 3' UTR element, each derived from a gene selected from the groups disclosed herein. Suitable 5' UTR elements are preferably selected from 5'-UTR elements derived from a 5' UTR of a gene selected from the group consisting of HSD17B4, ASAH1, ATP5A1, MP68, NDUFA4, NOSIP, RPL31, SLC7A3, TUBB4B and UBQLN2, preferably as defined herein. Suitable 3' UTR elements are preferably selected from 3' UTR elements derived from a 3' UTR of a gene selected from the group consisting of PSMB3, CASP1, COX6B1, GNAS, NDUFA1 and RPS9, preferably as defined herein. Further, the artificial nucleic acid molecules of the invention may optionally comprise at least one coding region operably linked to said 3'UTR element and said 5' UTR element. Preferably, the inventive artificial nucleic acid molecules may therefore comprise, in a 5'→3' direction, a 5'-UTR element as defined herein, operably linked to a coding region (cds) encoding a (poly-)peptide or protein of interest, and a 3' UTR element, operably linked to said coding region:

[0039] 5'-UTR - cds - 3' UTR .

[0040] Typically, the 5'- and / or 3'-UTR elements of the inventive artificial nucleic acid molecules may be "heterologous" to the at least one coding sequence. The term "heterologous" is used herein to refer to a nucleic acid sequence that is typically derived from a different species than a reference nucleic acid sequence. A "heterologous sequence" may thus be derived from a gene that is of a different origin as compared to a reference sequence, and may typically differ, in its sequence of nucleic acids, from the reference sequence and / or may encode a different gene product.

[0041] UTRs

[0042] 5' UTR

[0043] The artificial nucleic acid described herein comprises at least one 5 -UTR element derived from a 5' UTR of a gene as indicated herein, or a homolog, variant, fragment or derivative thereof.

[0044] The term "5'-UTR" refers to a part of a nucleic acid molecule, which is located 5' (i.e. "upstream") of an open reading frame and which is not translated into protein. In the context of the present invention, a 5'-UTR starts with the transcriptional start site and ends one nucleotide before the start codon of the open reading frame. The 5'-UTR may comprise elements for regulating gene expression, also called "regulatory elements". Such regulatory elements may be, for example, ribosomal binding sites. The 5'-UTR may be post-transcriptionally modified, for example by addition of a 5'- Cap. Thus, 5'-UTRs may preferably correspond to the sequence of a nucleic acid, in particular a mature mRNA, which is located between the 5'-Cap and the start codon, and more specifically to a sequence, which extends from a nucleotide located 3' to the 5'-Cap, preferably from the nucleotide located immediately 3' to the 5'-Cap, to a nucleotide located 5' to the start codon of the protein coding sequence (transcriptional start site), preferably to the nucleotide located immediately 5' to the start codon of the protein coding sequence (transcriptional start site). The nucleotide located immediately 3' to the 5'-Cap of a mature mRNA typically corresponds to the transcriptional start site. 5' UTRs typically have a length of less than 500, 400, 300, 250 or less than 200 nucleotides. In some embodiments its length may be in the range of at least 10, 20, 30 or 40, preferably up to 100 or 150, nucleotides.

[0045] Preferably, the at least one 5'UTR element comprises or consists of a nucleic acid sequence derived from the 5' UTR of a chordate gene, preferably a vertebrate gene, more preferably a mammalian gene, most preferably a human gene, or from a variant of the 3'UTR of a chordate gene, preferably a vertebrate gene, more preferably a mammalian gene, most preferably a human gene.

[0046] Some of the 5'UTR elements specified herein may be derived from the 5'UTR of a TOP gene or from a homolog, variant or fragment thereof. "TOP genes" are typically characterized by the presence of a 5' terminal oligo pyrimidine tract (TOP), and further, typically by a growth-associated translational regulation. However, TOP genes with a tissue specific translational regulation are also known. mRNA that contains a STOP is often referred to as TOP mRNA. Accordingly, genes that provide such messenger RNAs are referred to as TOP genes. TOP sequences have, for example, been found in genes and mRNAs encoding peptide elongation factors and ribosomal proteins. The 5'terminal oligo pyrimidine tract ("5TOP" or "TOP") is typically a stretch of pyrimidine nucleotides located in the 5' terminal region of a nucleic acid molecule, such as the 5' terminal region of certain mRNA molecules or the 5' terminal region of a functional entity, e.g. the transcribed region, of certain genes. The 5'UTR of a TOP gene corresponds to the sequence of a 5'UTR of a mature mRNA derived from a TOP gene, which preferably extends from the nucleotide located 3' to the 5'-CAP to the nucleotide located 5' to the start codon. The TOP sequence typically starts with a cytidine, which usually corresponds to the transcriptional start site, and is followed by a stretch of usually about 3 to 30 pyrimidine nucleotides. The pyrimidine stretch and thus the 5' TOP ends one nucleotide 5' to the first purine nucleotide located downstream of the TOP.

[0047] A 5'UTR of a TOP gene typically does not comprise any start codons, preferably no upstream AUGs (uAUGs) or upstream open reading frames (uORFs). Therein, upstream AUGs and upstream open reading frames are typically understood to be AUGs and open reading frames that occur 5' of the start codon (AUG) of the open reading frame that should be translated. The 5'UTRs of TOP genes are generally rather short. The lengths of 5'UTRs of TOP genes may vary between 20 nucleotides up to 500 nucleotides, and are typically less than about 200 nucleotides, preferably less than about 150 nucleotides, more preferably less than about 100 nucleotides. For example, a TOP may comprise 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30 or even more nucleotides. As used herein, the term "TOP motif" refers to a nucleic acid sequence which corresponds to a 5TOP as defined above. Thus, a "TOP motif" is preferably a stretch of pyrimidine nucleotides having a length of 3-30 nucleotides. Preferably, the TOP-motif consists of at least 3, preferably at least 4, more preferably at least 6, more preferably at least 7, and most preferably at least 8 pyrimidine nucleotides, wherein the stretch of pyrimidine nucleotides preferably starts at its 5'end with a cytosine nucleotide. In TOP genes and TOP mRNAs, the "TOP-motif" preferably starts at its 5'end with the transcriptional start site and ends one nucleotide 5' to the first purine residue in said gene or mRNA. A "TOP motif" is preferably located at the 5'end of a sequence, which represents a 5'UTR, or at the 5'end of a sequence, which codes for a 5'UTR. Thus, preferably, a stretch of 3 or more pyrimidine nucleotides is called "TOP motif" if this stretch is located at the 5'end of a respective sequence, such as the artificial nucleic acid molecule, the 5'UTR element of the artificial nucleic acid molecule, or the nucleic acid sequence which is derived from the 5'UTR of a TOP gene as described herein. In other words, a stretch of 3 or more pyrimidine nucleotides, which is not located at the 5'-end of a 5'UTR or a 5'UTR element but anywhere within a 5'UTR or a 5'UTR element, is preferably not referred to as "TOP motif".

[0048] In one embodiment, the 5'-end of an mRNA is "gggaga".

[0049] The 5'UTR elements derived from 5'UTRs of TOP genes exemplified herein may preferably lack a TOP-motif or a 5TOP, as defined above. Thus, the nucleic acid sequence of the 5'UTR element, which is derived from a 5'UTR of a TOP gene, may terminate at its 3'-end with a nucleotide located at position 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 upstream of the start codon (e.g. A(U / T)G) of the gene or mRNA it is derived from. Thus, the 5'UTR element does not comprise any part of the protein coding sequence. Thus, preferably, the only amino acid coding part of the artificial nucleic acid is provided by the coding sequence.

[0050] Particular 5'-UTR elements envisaged in accordance with the present invention are described in detail below.

[0051] HSD17B4-derived 5' UTR elements

[0052] Artificial nucleic acids according to the invention may comprise a 5'UTR element derived from a 5'UTR of a gene encoding a 17-beta-hydroxysteroid dehydrogenase 4, or a homolog, variant, fragment or derivative thereof, preferably lacking the 5TOP motif.

[0053] Such 5'UTR elements preferably comprise or consist of a nucleic acid sequence which is derived from the 5'UTR of a 17- beta-hydroxysteroid dehydrogenase 4 (also referred to as peroxisomal multifunctional enzyme type 2) gene, preferably from a vertebrate, more preferably mammalian, most preferably human 17-beta-hydroxysteroid dehydrogenase 4 (HSD17B4) gene, or a homolog, variant, fragment or derivative thereof, wherein preferably the 5'UTR element does not comprise the 5TOP of said gene. Said gene may preferably encode a 17-beta-hydroxysteroid dehydrogenase 4 protein corresponding to human 17-beta-hydroxysteroid dehydrogenase 4 (UniProt Ref. No. Q9BPX1, entry version #139 of August 30, 2017), or a homolog, variant, fragment or derivative thereof.

[0054] Accordingly, artificial nucleic acids according to the invention may comprise a 5'UTR element derived from a HSD17B4 gene, in particular derived from the 5' UTR of said HSD17B4 gene, preferably wherein said 5'UTR element comprises or consists of a DNA sequence according to SEQ ID NO: 1 or a homolog, variant, fragment or derivative thereof, in particular a DNA sequence having, in increasing order of preference, at least 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%, preferably of at least 70%, more preferably of at least 80%, even more preferably at least 85%, even more preferably of at least 90% and most preferably of at least 95% or even 97%, sequence identity to a nucleic acid sequence according to SEQ ID NO: 1, or wherein said 5'UTR element comprises or consists of an RNA sequence according to SEQ ID NO: 2, or a or a homolog, variant, fragment or derivative thereof, in particular an RNA sequence having, in increasing order of preference, at least at least 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%, preferably of at least 70%, more preferably of at least 80%, even more preferably at least 85%, even more preferably of at least 90% and most preferably of at least 95% or even 97%, sequence identity to a nucleic acid sequence according to SEQ ID NO: 2. ASAHl -derived 5' UTR elements

[0055] Artificial nucleic acids according to the invention may comprise a 5'UTR element derived from a 5'UTR of a gene encoding acid ceramidase (ASAHl), or a homolog, variant, fragment or derivative thereof.

[0056] Such 5'UTR elements preferably comprise or consist of a nucleic acid sequence which is derived from the 5'UTR of an acid ceramidase (ASAHl) gene, preferably a vertebrate, more preferably mammalian, most preferably human acid ceramidase (ASAHl) gene, or a homolog, variant, fragment or derivative thereof. Said gene preferably encodes an acid ceramidase protein corresponding to human acid ceramidase (UniProt Ref. No. Q13510, entry version #177 of June 7, 2017), or a homolog, variant, fragment or derivative thereof.

[0057] Accordingly, artificial nucleic acids according to the invention may comprise a 5'UTR element derived from an ASAHl gene, in particular derived from the 5' UTR of said ASAHl gene, preferably wherein said 5'UTR element comprises or consists of a DNA sequence according to SEQ ID NO: 3 or a homolog, variant, fragment or derivative thereof, in particular a DNA sequence having, in increasing order of preference, at least 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%, preferably of at least 70%, more preferably of at least 80%, even more preferably at least 85%, even more preferably of at least 90% and most preferably of at least 95% or even 97%, sequence identity to a nucleic acid sequence according to SEQ ID NO: 3, or wherein said 5'UTR element comprises or consists of an RNA sequence according to SEQ ID NO: 4, or a or a homolog, variant, fragment or derivative thereof, in particular an RNA sequence having, in increasing order of preference, at least at least 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%, preferably of at least 70%, more preferably of at least 80%, even more preferably at least 85%, even more preferably of at least 90% and most preferably of at least 95% or even 97%, sequence identity to a nucleic acid sequence according to SEQ ID NO: 4.

[0058] A TP5A1 -derived 5'- UTR elements

[0059] Artificial nucleic acids according to the invention may comprise a 5'UTR element which is derived from a 5'UTR of a gene encoding mitochondrial ATP synthase subunit alpha (ATP5A1), or a homolog, variant, fragment or derivative thereof, wherein said 5' UTR element preferably lacks the 5TOP motif.

[0060] Such 5'UTR elements preferably comprise or consist of a nucleic acid sequence which is derived from the 5'UTR of a mitochondrial ATP synthase subunit alpha (ATP5A1) gene, preferably from a vertebrate, more preferably a mammalian and most preferably a human mitochondrial ATP synthase subunit alpha (ATP5A1) gene, or a homolog, variant, fragment or derivative thereof, wherein the 5'UTR element preferably does not comprise the STOP of said gene. Said gene may preferably encode a mitochondrial ATP synthase subunit alpha protein corresponding to human acid mitochondrial ATP synthase subunit alpha (UniProt Ref. No. P25705, entry version #208 of August 30, 2017), or a homolog, variant, fragment or derivative thereof.

[0061] Accordingly, artificial nucleic acids according to the invention may comprise a 5'UTR element derived from a ATP5A1 gene, in particular derived from the 5' UTR of said ATP5A1 gene, preferably wherein said 5'UTR element comprises or consists of a DNA sequence according to SEQ ID NO: 5 or a homolog, variant, fragment or derivative thereof, in particular a DNA sequence having, in increasing order of preference, at least 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%, preferably of at least 70%, more preferably of at least 80%, even more preferably at least 85%, even more preferably of at least 90% and most preferably of at least 95% or even 97%, sequence identity to the nucleic acid sequence according to SEQ ID NO: 5, or wherein said 5'UTR element comprises or consists of an RNA sequence according to SEQ ID NO: 6, or a homolog, variant, fragment or derivative thereof, in particular an RNA sequence having, in increasing order of preference, at least at least 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%, preferably of at least 70%, more preferably of at least 80%, even more preferably at least 85%, even more preferably of at least 90% and most preferably of at least 95% or even 97%, sequence identity to the nucleic acid sequence according to SEQ ID NO: 6.

[0062] MP68-derived 5' UTR elements

[0063] Artificial nucleic acids according to the invention may comprise a 5'UTR element which is derived from a 5'UTR of a gene encoding MP68, or a homolog, variant, fragment or derivative thereof.

[0064] Such 5'UTR elements preferably comprise or consist of a nucleic acid sequence which is derived from the 5'UTR of a 6.8 kDa mitochondrial proteolipid (MP68) gene, preferably from a vertebrate, more preferably a mammalian and most preferably a human 6.8 kDa mitochondrial proteolipid (MP68) gene, or a homolog, variant, fragment or derivative thereof. Said gene may preferably encode a 6.8 kDa mitochondrial proteolipid (MP68) protein corresponding to human 6.8 kDa mitochondrial proteolipid (MP68) (UniProt Ref. No. P56378, entry version #127 of 15 February 2017), or a homolog, variant, fragment or derivative thereof.

[0065] Accordingly, artificial nucleic acids according to the invention may comprise a 5'UTR element derived from a MP68 gene, in particular derived from the 5' UTR of said MP68 gene, preferably wherein said 5'UTR element comprises or consists of a DNA sequence according to SEQ ID NO: 7 or a homolog, variant, fragment or derivative thereof, in particular a DNA sequence having, in increasing order of preference, at least 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%, preferably of at least 70%, more preferably of at least 80%, even more preferably at least 85%, even more preferably of at least 90% and most preferably of at least 95% or even 97%, sequence identity to the nucleic acid sequence according to SEQ ID NO: 7, or wherein said 5'UTR element comprises or consists of an RNA sequence according to SEQ ID NO: 8, or a homolog, variant, fragment or derivative thereof, in particular an RNA sequence having, in increasing order of preference, at least at least 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%, preferably of at least 70%, more preferably of at least 80%, even more preferably at least 85%, even more preferably of at least 90% and most preferably of at least 95% or even 97%, sequence identity to the nucleic acid sequence according to SEQ ID NO: 8.

[0066] NDUFA4-derived 5'- UTR elements

[0067] Artificial nucleic acids according to the invention may comprise a 5'UTR element which is derived from a 5'UTR of a gene encoding a Cytochrome c oxidase subunit (NDUFA4), or a homolog, fragment or variant thereof. Such 5'UTR elements preferably comprise or consist of a nucleic acid sequence which is derived from the 5'UTR of a Cytochrome c oxidase subunit (NDUFA4) gene, preferably from a vertebrate, more preferably a mammalian, most preferably a human Cytochrome c oxidase subunit (NDUFA4) gene, or a homolog, variant, fragment or derivative thereof. Said gene may preferably encode a Cytochrome c oxidase subunit (NDUFA4) protein corresponding to a human Cytochrome c oxidase subunit (NDUFA4) protein (UniProt Ref. No. 000483, entry version #149 of 30 August 2017).

[0068] Accordingly, artificial nucleic acids according to the invention may comprise a 5'UTR element derived from a NDUFA4 gene, wherein said 5'UTR element comprises or consists of a DNA sequence according to SEQ ID NO: 9 or a homolog, variant, fragment or derivative thereof, in particular a DNA sequence having, in increasing order of preference, at least 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%, preferably of at least 70%, more preferably of at least 80%, even more preferably at least 85%, even more preferably of at least 90% and most preferably of at least 95% or even 97%, sequence identity to the nucleic acid sequence according to SEQ ID NO: 9, or wherein said 5'UTR element comprises or consists of an RNA sequence according to SEQ ID NO: 10, or a homolog, variant, fragment or derivative thereof, in particular an RNA sequence having, in increasing order of preference, at least at least 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%, preferably of at least 70%, more preferably of at least 80%, even more preferably at least 85%, even more preferably of at least 90% and most preferably of at least 95% or even 97%, sequence identity to the nucleic acid sequence according to SEQ ID NO: 10.

[0069] NOSIP-derived 5' UTR elements

[0070] Artificial nucleic acids according to the invention may comprise a 5'UTR element which is derived from a 5'UTR of a gene encoding a Nitric oxide synthase-interacting (NOSIP) protein, or a homolog, variant, fragment or derivative thereof.

[0071] Such 5'UTR elements preferably comprise or consist of a nucleic acid sequence which is derived from the 5'UTR of a Nitric oxide synthase-interacting protein (NOSIP) gene, preferably from a vertebrate, more preferably a mammalian, most preferably a human Nitric oxide synthase-interacting protein (NOSIP) gene, or a homolog, variant, fragment or derivative thereof. Said gene may preferably encode a Nitric oxide synthase-interacting protein (NOSIP) protein corresponding to a human Nitric oxide synthase-interacting protein (NOSIP) protein (UniProt Ref. No. Q9Y314, entry version #130 of 7 June 2017).

[0072] Accordingly, artificial nucleic acids according to the invention may comprise a 5'UTR element derived from a NOSIP gene, wherein said 5'UTR element comprises or consists of a DNA sequence according to SEQ ID NO: 11 or a homolog, variant, fragment or derivative thereof, in particular a DNA sequence having, in increasing order of preference, at least 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%, preferably of at least 70%, more preferably of at least 80%, even more preferably at least 85%, even more preferably of at least 90% and most preferably of at least 95% or even 97%, sequence identity to the nucleic acid sequence according to SEQ ID NO: 11, or wherein said 5'UTR element comprises or consists of an RNA sequence according to SEQ ID NO: 12, or a homolog, variant, fragment or derivative thereof, in particular an RNA sequence having, in increasing order of preference, at least at least 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%, preferably of at least 70%, more preferably of at least 80%, even more preferably at least 85%, even more preferably of at least 90% and most preferably of at least 95% or even 97%, sequence identity to the nucleic acid sequence according to SEQ ID NO; 12.

[0073] RPL31 -derived 5'-UTR elements

[0074] Artificial nucleic acids according to the invention may comprise a 5'UTR element which is derived from a 5'UTR of a gene encoding a 60S ribosomal protein L31, or a homolog, variant, fragment or derivative thereof, wherein said 5' UTR element preferably lacks the 5TOP motif.

[0075] Such 5'UTR elements preferably comprise or consist of a nucleic acid sequence which is derived from the 5'UTR of a 60S ribosomal protein L31 (RPL31) gene, preferably from a vertebrate, more preferably a mammalian, most preferably a human 60S ribosomal protein L31 (RPL31) gene, or a homolog, variant, fragment or derivative thereof, wherein the 5'UTR element preferably does not comprise the 5TOP of said gene. Said gene may preferably encode a 60S ribosomal protein L31 (RPL31) corresponding to a human 60S ribosomal protein L31 (RPL31) (UniProt Ref. No. P62899, entry version #138 of 30 August 2017).

[0076] Accordingly, artificial nucleic acids according to the invention may comprise a 5'UTR element derived from a RPL31 gene, wherein said 5'UTR element comprises or consists of a DNA sequence according to SEQ ID NO: 13 or a homolog, variant, fragment or derivative thereof, in particular a DNA sequence having, in increasing order of preference, at least 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%, preferably of at least 70%, more preferably of at least 80%, even more preferably at least 85%, even more preferably of at least 90% and most preferably of at least 95% or even 97%, sequence identity to the nucleic acid sequence according to SEQ ID NO: 13, or wherein said 5'UTR element comprises or consists of an RNA sequence according to SEQ ID NO: 14, or a homolog, variant, fragment or derivative thereof, in particular an RNA sequence having, in increasing order of preference, at least at least 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%, preferably of at least 70%, more preferably of at least 80%, even more preferably at least 85%, even more preferably of at least 90% and most preferably of at least 95% or even 97%, sequence identity to the nucleic acid sequence according to SEQ ID NO: 14.

[0077] SLC7A3-de ved 5'-UTR elements

[0078] Artificial nucleic acids according to the invention may comprise a 5'UTR element which is derived from a 5'UTR of a gene encoding a cationic amino acid transporter 3 (solute carrier family 7 member 3, SLC7A3) protein, or a homolog, variant, fragment or derivative thereof.

[0079] Such 5'UTR elements preferably comprise or consist of a nucleic acid sequence which is derived from the 5'UTR of a cationic amino acid transporter 3 (SLC7A3) gene, preferably from a vertebrate, more preferably a mammalian, most preferably a human cationic amino acid transporter 3 (SLC7A3) gene, or a homolog, variant, fragment or derivative thereof. Said gene may preferably encode a cationic amino acid transporter 3 (SLC7A3) protein corresponding to a human cationic amino acid transporter 3 (SLC7A3) protein (UniProt Ref. No. Q8WY07, entry version #139 of 30 August 2017). Accordingly, artificial nucleic acids according to the invention may comprise a 5'UTR element derived from a SLC7A3 gene, wherein said 5'UTR element comprises or consists of a DNA sequence according to SEQ ID NO: 15 or a homolog, variant, fragment or derivative thereof, in particular a DNA sequence having, in increasing order of preference, at least 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%, preferably of at least 70%, more preferably of at least 80%, even more preferably at least 85%, even more preferably of at least 90% and most preferably of at least 95% or even 97%, sequence identity to the nucleic acid sequence according to SEQ ID NO: 15, or wherein said 5'UTR element comprises or consists of an RNA sequence according to SEQ ID NO: 16, or a homolog, variant, fragment or derivative thereof, in particular an RNA sequence having, in increasing order of preference, at least at least 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%, preferably of at least 70%, more preferably of at least 80%, even more preferably at least 85%, even more preferably of at least 90% and most preferably of at least 95% or even 97%, sequence identity to the nucleic acid sequence according to SEQ ID NO: 16.

[0080] TUBB4B-derived 5' UTR elements

[0081] Artificial nucleic acids according to the invention may comprise a 5'UTR element which is derived from a 5'UTR of a gene encoding a tubulin beta-4B chain (TUBB4B) protein, or a homolog, variant, fragment or derivative thereof.

[0082] Such 5'UTR elements preferably comprise or consist of a nucleic acid sequence which is derived from the 5'UTR of a tubulin beta-4B chain (TUBB4B) gene, preferably from a vertebrate, more preferably a mammalian, most preferably a human tubulin beta-4B chain (TUBB4B) gene, or a homolog, variant, fragment or derivative thereof. Said gene may preferably encode a tubulin beta-4B chain (TUBB4B) protein corresponding to a human tubulin beta-4B chain (TUBB4B) protein (UniProt Ref. No. Q8WY07, entry version #142 of 30 August 2017).

[0083] Accordingly, artificial nucleic acids according to the invention may comprise a 5'UTR element derived from a tubulin beta- 4B chain (TUBB4B) gene, wherein said 5'UTR element comprises or consists of a DNA sequence according to SEQ ID NO: 17 or a homolog, variant, fragment or derivative thereof, in particular a DNA sequence having, in increasing order of preference, at least 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%, preferably of at least 70%, more preferably of at least 80%, even more preferably at least 85%, even more preferably of at least 90% and most preferably of at least 95% or even 97%, sequence identity to the nucleic acid sequence according to SEQ ID NO: 17, or wherein said 5'UTR element comprises or consists of an RNA sequence according to SEQ ID NO: 18, or a homolog, variant, fragment or derivative thereof, in particular an RNA sequence having, in increasing order of preference, at least at least 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%, preferably of at least 70%, more preferably of at least 80%, even more preferably at least 85%, even more preferably of at least 90% and most preferably of at least 95% or even 97%, sequence identity to the nucleic acid sequence according to SEQ ID NO: 18.

[0084] UBQLN2-derived 5'-UTR elements

[0085] Artificial nucleic acids according to the invention may comprise a 5'UTR element which is derived from a 5'UTR of a gene encoding an ubiquilin-2 (UBQLN2) protein, or a homolog, variant, fragment or derivative thereof. Such 5'UTR elements preferably comprise or consist of a nucleic acid sequence which is derived from the 5'UTR of a ubiquiiin-2 (UBQLN2) gene, preferably from a vertebrate, more preferably a mammalian, most preferably a human ubiquilin-2 (UBQLN2) gene, or a homolog, variant, fragment or derivative thereof. Said gene may preferably encode an ubiquilin-2 (UBQLN2) protein corresponding to a human ubiquilin-2 (UBQLN2) protein (UniProt Ref. No. Q9UHD9, entry version #151 of 30 August 2017).

[0086] Accordingly, artificial nucleic acids according to the invention may comprise a 5'UTR element derived from a ubiquilin-2 (UBQLN2) gene, wherein said 5'UTR element comprises or consists of a DNA sequence according to SEQ ID NO: 19 or a homolog, variant, fragment or derivative thereof, in particular a DNA sequence having, in increasing order of preference, at least 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%, preferably of at least 70%, more preferably of at least 80%, even more preferably at least 85%, even more preferably of at least 90% and most preferably of at least 95% or even 97%, sequence identity to the nucleic acid sequence according to SEQ ID NO: 19, or wherein said 5'UTR element comprises or consists of an RNA sequence according to SEQ ID NO: 20, or a homolog, variant, fragment or derivative thereof, in particular an RNA sequence having, in increasing order of preference, at least at least 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%, preferably of at least 70%, more preferably of at least 80%, even more preferably at least 85%, even more preferably of at least 90% and most preferably of at least 95% or even 97%, sequence identity to the nucleic acid sequence according to SEQ ID NO: 20.

[0087] 3' UTR

[0088] The artificial nucleic acid described herein further comprises at least one 3 -UTR element derived from a 3' UTR of a gene as defined herein, or a homolog, variant or fragment of said gene. The term "3 -UTR" refers to a part of a nucleic acid molecule, which is located 3' (i.e. "downstream") of an open reading frame and which is not translated into protein. In the context of the present invention, a 3'-UTR corresponds to a sequence which is located between the stop codon of the protein coding sequence, preferably immediately 3' to the stop codon of the protein coding sequence, and the poly(A) sequence of the artificial nucleic acid (RNA) molecule.

[0089] Preferably, the at least one 3'UTR element comprises or consists of a nucleic acid sequence derived from the 3'UTR of a chordate gene, preferably a vertebrate gene, more preferably a murine gene, even more preferably a mammalian gene, most preferably a human gene, or from a variant of the 3'UTR of a chordate gene, preferably a vertebrate gene, more preferably a murine gene, even more preferably a mammalian gene, most preferably a human gene.

[0090] PSMB3-derived 3'-UTR elements

[0091] Artificial nucleic acids according to the invention may comprise a 3'UTR element which is derived from a 3'UTR of a gene encoding a proteasome subunit beta type-3 (PSMB3) protein, or a homolog, variant, fragment or derivative thereof.

[0092] Such 3'UTR elements preferably comprises or consists of a nucleic acid sequence which is derived from the 3'UTR of a proteasome subunit beta type-3 (PSMB3) gene, preferably from a vertebrate, more preferably a mammalian, most preferably a human proteasome subunit beta type-3 (PSMB3) gene, or a homolog, variant, fragment or derivative thereof. Said gene may preferably encode a proteasome subunit beta type-3 (PSMB3) protein corresponding to a human proteasome subunit beta type-3 (PSMB3) protein (UniProt Ref. No.

[0093] P49720, entry version #183 of 30 August 2017).

[0094] Accordingly, artificial nucleic acids according to the invention may comprise a 3'UTR element derived from a PS B3 gene, wherein said 3'UTR element comprises or consists of a DNA sequence according to SEQ ID NO: 23 or a homolog, variant, fragment or derivative thereof, in particular a DNA sequence having, in increasing order of preference, at least 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%, preferably of at least 70%, more preferably of at least 80%, even more preferably at least 85%, even more preferably of at least 90% and most preferably of at least 95% or even 97%, sequence identity to the nucleic acid sequence according to SEQ ID NO: 23, or wherein said 3'UTR element comprises or consists of an RNA sequence according to SEQ ID NO: 24, or a homolog, variant, fragment or derivative thereof, in particular an RNA sequence having, in increasing order of preference, at least at least 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%, preferably of at least 70%, more preferably of at least 80%, even more preferably at least 85%, even more preferably of at least 90% and most preferably of at least 95% or even 97%, sequence identity to the nucleic acid sequence according to SEQ ID NO: 24.

[0095] CASP1 -derived 3'-UTR elements

[0096] Artificial nucleic acids according to the invention may comprise a 3'UTR element which is derived from a 3'UTR of a gene encoding a Caspase-1 (CASP1) protein, or a homolog, variant, fragment or derivative thereof.

[0097] Such 3'UTR elements preferably comprises or consists of a nucleic acid sequence which is derived from the 3'UTR of a Caspase-1 (CASP1) gene, preferably from a vertebrate, more preferably a mammalian, most preferably a human Caspase- 1 (CASP1) gene, or a homolog, variant, fragment or derivative thereof.

[0098] Accordingly, artificial nucleic acids according to the invention may comprise a 3'UTR element derived from a CASP1 gene, wherein said 3'UTR element comprises or consists of a DNA sequence according to SEQ ID NO: 25 or a homolog, variant, fragment or derivative thereof, in particular a DNA sequence having, in increasing order of preference, at least 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%, preferably of at least 70%, more preferably of at least 80%, even more preferably at least 85%, even more preferably of at least 90% and most preferably of at least 95% or even 97%, sequence identity to the nucleic acid sequence according to SEQ ID NO: 25, or wherein said 3'UTR element comprises or consists of an RNA sequence according to SEQ ID NO: 26, or a homolog, variant, fragment or derivative thereof, in particular an RNA sequence having, in increasing order of preference, at least at least 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%, preferably of at least 70%, more preferably of at least 80%, even more preferably at least 85%, even more preferably of at least 90% and most preferably of at least 95% or even 97%, sequence identity to the nucleic acid sequence according to SEQ ID NO: 26. COX6B1 -derived 3 "-UTR elements

[0099] Artificial nucleic acids according to the invention may comprise a 3'UTR element which is derived from a 3'UTR of a COX6B1 gene encoding a cytochrome c oxidase subunit 6B1 (COX6B1) protein, or a homolog, variant, fragment or derivative thereof.

[0100] Such 3'UTR elements preferably comprises or consists of a nucleic acid sequence which is derived from the 3'UTR of a cytochrome c oxidase subunit 6B1 (COX6B1) gene, preferably from a vertebrate, more preferably a mammalian, most preferably a human cytochrome c oxidase subunit 6B1 (COX6B1) gene, or a homolog, variant, fragment or derivative thereof. Said gene may preferably encode a cytochrome c oxidase subunit 6B1 (COX6B1) protein corresponding to a human cytochrome c oxidase subunit 6B1 (COX6B1) protein (UniProt Ref. No. P14854, entry version #166 of 30 August 2017).

[0101] Accordingly, artificial nucleic acids according to the invention may comprise a 3'UTR element derived from a COX6B1 gene, wherein said 3'UTR element comprises or consists of a DNA sequence according to SEQ ID NO: 27 or a homolog, variant, fragment or derivative thereof, in particular a DNA sequence having, in increasing order of preference, at least 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%, preferably of at least 70%, more preferably of at least 80%, even more preferably at least 85%, even more preferably of at least 90% and most preferably of at least 95% or even 97%, sequence identity to the nucleic acid sequence according to SEQ ID NO: 27, or wherein said 3'UTR element comprises or consists of an RNA sequence according to SEQ ID NO: 28, or a homolog, variant, fragment or derivative thereof, in particular an RNA sequence having, in increasing order of preference, at least at least 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%, preferably of at least 70%, more preferably of at least 80%, even more preferably at least 85%, even more preferably of at least 90% and most preferably of at least 95% or even 97%, sequence identity to the nucleic acid sequence according to SEQ ID NO: 28.

[0102] GNAS-derived 3'-UTR elements

[0103] Artificial nucleic acids according to the invention may comprise a 3'UTR element derived from a 3'UTR of a gene encoding a Guanine nucleotide-binding protein G(s) subunit alpha isoforms short (GNAS) protein, or a homolog, variant, fragment or derivative thereof.

[0104] Such 3'UTR elements preferably comprises or consists of a nucleic acid sequence which is derived from the 3'UTR of a Guanine nucleotide-binding protein G(s) subunit alpha isoforms short (GNAS) gene, preferably from a vertebrate, more preferably a mammalian, most preferably a human Guanine nucleotide-binding protein G(s) subunit alpha isoforms short (GNAS) gene, or a homolog, variant, fragment or derivative thereof. Said gene may preferably encode a Guanine nucleotide-binding protein G(s) subunit alpha isoforms short (GNAS) protein corresponding to a human Guanine nucleotide- binding protein G(s) subunit alpha isoforms short (GNAS) protein (UniProt Ref. No. P63092, entry version #153 of 30 August 2017).

[0105] Accordingly, artificial nucleic acids according to the invention may comprise a 3' UTR element derived from a GNAS gene, wherein said 3'UTR element comprises or consists of a DNA sequence according to SEQ ID NO: 29 or a homolog, variant, fragment or derivative thereof, in particular a DNA sequence having, in increasing order of preference, at least 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%, preferably of at least 70%, more preferably of at least 80%, even more preferably at least 85%, even more preferably of at least 90% and most preferably of at least 95% or even 97%, sequence identity to the nucleic acid sequence according to SEQ ID NO: 29, or wherein said 3'UTR element comprises or consists of an RNA sequence according to SEQ ID NO: 30, or a homolog, variant, fragment or derivative thereof, in particular an RNA sequence having, in increasing order of preference, at least at least 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%, preferably of at least 70%, more preferably of at least 80%, even more preferably at least 85%, even more preferably of at least 90% and most preferably of at least 95% or even 97%, sequence identity to the nucleic acid sequence according to SEQ ID NO: 30.

[0106] NDUFA 1 -derived 3' UTR elements

[0107] Artificial nucleic acids according to the invention may comprise a 3'UTR element which is derived from a 3'UTR of a gene encoding a NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 1 (NDUFA1) protein, or a homolog, variant, fragment or derivative thereof.

[0108] Such 3'UTR elements preferably comprises or consists of a nucleic acid sequence which is derived from the 3'UTR of a NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 1 (NDUFA1) gene, preferably from a vertebrate, more preferably a mammalian, most preferably a human NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 1 (NDUFA1) gene, or a homolog, variant, fragment or derivative thereof. Said gene may preferably encode a NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 1 (NDUFA1) protein corresponding to a human NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 1 (NDUFA1) protein (UniProt Ref. No. 015239, entry version #152 of 30 August 2017).

[0109] Accordingly, artificial nucleic acids according to the invention may comprise a 3'UTR element derived from a NDUFA1 gene, wherein said 3'UTR element comprises or consists of a DNA sequence according to SEQ ID NO: 31 or a homolog, variant, fragment or derivative thereof, in particular a DNA sequence having, in increasing order of preference, at least 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%, preferably of at least 70%, more preferably of at least 80%, even more preferably at least 85%, even more preferably of at least 90% and most preferably of at least 95% or even 97%, sequence identity to the nucleic acid sequence according to SEQ ID NO: 31, or wherein said 3'UTR element comprises or consists of an RNA sequence according to SEQ ID NO: 32, or a homolog, variant, fragment or derivative thereof, in particular an RNA sequence having, in increasing order of preference, at least at least 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%, preferably of at least 70%, more preferably of at least 80%, even more preferably at least 85%, even more preferably of at least 90% and most preferably of at least 95% or even 97%, sequence identity to the nucleic acid sequence according to SEQ ID NO: 32. RPS9-derived 3'-UTRs

[0110] Artificial nucleic acids according to the invention may comprise a 3'UTR element which comprises or consists of a nucleic acid sequence, which is derived from a 3'UTR of a gene encoding a 40S ribosomal protein S9 (RPS9) protein, or a homolog, variant, fragment or derivative thereof.

[0111] Such 3'UTR elements preferably comprises or consists of a nucleic acid sequence which is derived from the 3'UTR of a 40S ribosomal protein S9 (RPS9) gene, preferably from a vertebrate, more preferably a mammalian, most preferably a human 40S ribosomal protein S9 (RPS9) gene, or a homolog, variant, fragment or derivative thereof. Said gene may preferably encode a 40S ribosomal protein S9 (RPS9) protein corresponding to a 40S ribosomal protein S9 (RPS9) protein (UniProt Ref. No. P46781, entry version #179 of 30 August 2017).

[0112] Accordingly, artificial nucleic acids according to the invention may comprise a 3'UTR element derived from a RPS9 gene, wherein said 3'UTR element comprises or consists of a DNA sequence according to SEQ ID NO: 33 or a homolog, variant, fragment or derivative thereof, in particular a DNA sequence having, in increasing order of preference, at least 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%, preferably of at least 70%, more preferably of at least 80%, even more preferably at least 85%, even more preferably of at least 90% and most preferably of at least 95% or even 97%, sequence identity to the nucleic acid sequence according to SEQ ID NO: 33, or wherein said 5'UTR element comprises or consists of an RNA sequence according to SEQ ID NO: 34, or a homolog, variant, fragment or derivative thereof, in particular an RNA sequence having, in increasing order of preference, at least at least 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%, preferably of at least 70%, more preferably of at least 80%, even more preferably at least 85%, even more preferably of at least 90% and most preferably of at least 95% or even 97%, sequence identity to the nucleic acid sequence according to SEQ ID NO: 34.

[0113] UTR combinations

[0114] Preferably, the at least one 5'UTR element and the at least one 3'UTR element act synergistically to modulate, more preferably induce or enhance, the expression of the at least one coding sequence operably linked to said UTR elements. It is envisaged herein to utilize each 5'- and 3'-UTR element exemplified herein in any conceivable combination.

[0115] Preferred combinations of 5'- and 3'-UTR elements are listed in table 1 below.

[0116] Table 1: UTR combinations

[0117] # 5' UTR element SEQ ID NO: 3' UTR element SEQ ID NO:

[0118] derived from derived from

[0119] 1 ASAH1 4 CASP1 26

[0120] 2 ASAH1 4 COX6B1 28

[0121] 3 ASAH1 4 GNAS 30

[0122] 4 ASAH1 4 NDUFA1 32

[0123] 5 ASAH1 4 PSMB3 24 5' UT element SEQ ID NO: 3' UTR element SEQ ID NO: derived from derived from

[0124] ASAH1 4 RPS9 34

[0125] ATP5A1 6 CASP1 26

[0126] ATP5A1 6 COX6B1 28

[0127] ATP5A1 6 GNAS 30

[0128] ATP5A1 6 NDUFA1 32

[0129] ATP5A1 6 PSMB3 24

[0130] ATP5A1 6 RPS9 34

[0131] HSD17B4 2 CASP1 26

[0132] HSD17B4 2 COX6B1 28

[0133] HSD17B4 2 GNAS 30

[0134] HSD17B4 2 NDUFA1 32

[0135] HSD17B4 2 PSMB3 24

[0136] HSD17B4 2 RPS9 34

[0137] MP68 8 CASP1 26

[0138] MP68 8 COX6B1 28

[0139] MP68 8 GNAS 30

[0140] MP68 8 NDUFA1 32

[0141] MP68 8 PSMB3 24

[0142] P68 8 RPS9 34

[0143] NDUFA4 10 CASP1 26

[0144] NDUFA4 10 COX6B1 28

[0145] NDUFA4 10 GNAS 30

[0146] NDUFA4 10 NDUFA1 32

[0147] NDUFA4 10 PSMB3 24

[0148] NDUFA4 10 RPS9 34

[0149] NOSIP 12 CASP1 26

[0150] NOSIP 12 COX6B1 28

[0151] NOSIP 12 GNAS 30

[0152] NOSIP 12 NDUFA1 32

[0153] NOSIP 12 PSMB3 24

[0154] NOSIP 12 RPS9 34

[0155] RPL31 14 CASP1 26

[0156] RPL31 14 COX6B1 28

[0157] RPL31 14 GNAS 30

[0158] RPL31 14 NDUFA1 32

[0159] RPL31 14 PSMB3 24

[0160] RPL31 14 RPS9 34

[0161] SLC7A3 16 CASP1 26

[0162] SLC7A3 16 COX6B1 28 # 5' UTR element SEQ ID NO: 3' UTR element SEQ ID NO:

[0163] derived from derived from

[0164] 45 SLC7A3 16 GNAS 30

[0165] 46 SLC7A3 16 NDUFA1 32

[0166] 47 SLC7A3 16 PSMB3 24

[0167] 48 SLC7A3 16 RPS9 34

[0168] 49 TUBB4B 18 CASP1 26

[0169] 50 TUBB4B 18 COX6B1 28

[0170] 51 TUBB4B 18 GNAS 30

[0171] 52 TUBB4B 18 NDUFA1 32

[0172] 53 TUBB4B 18 PSMB3 24

[0173] 54 TUBB4B 18 RPS9 34

[0174] 55 UBQLN2 20 CASP1 26

[0175] 56 UBQLN2 20 COX6B1 28

[0176] 57 UBQLN2 20 GNAS 30

[0177] 58 UBQLN2 20 NDUFA1 32

[0178] 59 UBQLN2 20 PSMB3 24

[0179] 60 UBQLN2 20 RPS9 34

[0180] Especially the following UTR-combinations are preferred: 5'UTR: ASAH1 + 3'UTR: CASP1; 5'UTR: ASAH1 + 3'UTR: COX6B1; 5'UTR: ASAH1 + 3'UTR: Gnas; 5'UTR: ASAH1 + 3'UTR: Ndufal.l; 5'UTR: ASAH1 + 3'UTR: PSMB3; 5'UTR: ASAH1 + 3'UTR: RPS9; 5'UTR: ATP5A1 + 3'UTR: CASP1; 5'UTR: ATP5A1 + 3'UTR: COX6B1; 5'UTR: ATP5A1 + 3'UTR: Gnas; 5'UTR: ATP5A1 + 3'UTR: Ndufal.l; 5'UTR: ATP5A1 + 3'UTR: PSMB3; 5'UTR: ATP5A1 + 3'UTR: RPS9; 5'UTR: HSD17B4 + 3'UTR: CASP1; 5'UTR: HSD17B4 + 3'UTR: COX6B1; 5'UTR: HSD17B4 + 3'UTR: Ndufal.l; 5'UTR: HSD17B4 + 3'UTR: PSMB3; 5'UTR: HSD17B4 + 3'UTR: RPS9; 5'UTR: Mp68 + 3'UTR: CASP1; 5'UTR: Mp68 + 3'UTR: COX6B1; 5'UTR: p68 + 3'UTR: Gnas; 5'UTR: Mp68 + 3'UTR: Ndufal.l; 5'UTR: Mp68 + 3'UTR: PSMB3; 5'UTR: Mp68 + 3'UTR: RPS9; 5'UTR: Ndufa4 + 3'UTR: CASP1; 5'UTR: Ndufa4 + 3'UTR: COX6B1; 5'UTR: Ndufa4 + 3'UTR: Gnas; 5'UTR: Ndufa4 + 3'UTR: Ndufal.l; 5'UTR: Ndufa4 + 3'UTR: PSMB3; 5'UTR: Ndufa4 + 3'UTR: RPS9; 5'UTR: Nosip + 3'UTR: CASP1; 5'UTR: Nosip + 3'UTR: COX6B1; 5'UTR: Nosip + 3'UTR: Gnas; 5'UTR: Nosip + 3'UTR: Ndufal.l; 5'UTR: Nosip + 3'UTR: PSMB3; 5'UTR: Nosip + 3'UTR: RPS9; 5'UTR: Rpl31 + 3'UTR: CASP1; 5'UTR: Rpl31 + 3'UTR: COX6B1; 5'UTR: Rpl31 + 3'UTR: Gnas; 5'UTR: Rpl31 + 3'UTR: Ndufal.l; 5'UTR: Rpl31 + 3'UTR: PSMB3; 5'UTR: Rpl31 + 3'UTR: RPS9; 5'UTR: Slc7a3 + 3'UTR: CASP1; 5'UTR: Slc7a3 + 3'UTR: COX6B1; 5'UTR: Slc7a3 + 3'UTR: Ndufal.l; 5'UTR: Slc7a3 + 3'UTR: PSMB3; 5'UTR: Slc7a3 + 3'UTR: RPS9; 5'UTR: TUBB4B + 3'UTR: CASP1; 5'UTR: TUBB4B + 3'UTR: COX6B1; 5'UTR: TUBB4B + 3'UTR: Gnas; 5'UTR: TUBB4B + 3'UTR: Ndufal.l; 5'UTR: TUBB4B + 3'UTR: PSMB3; 5'UTR: TUBB4B + 3'UTR: RPS9; 5'UTR: Ubqln2 + 3'UTR: CASP1; 5'UTR: Ubqln2 + 3'UTR: COX6B1; 5'UTR: Ubqln2 + 3'UTR: Gnas; 5'UTR: Ubqln2 + 3'UTR: Ndufal.l; 5'UTR: Ubqln2 + 3'UTR: PSMB3; and 5'UTR: Ubqln2 + 3'UTR: RPS9, preferably the UTR-combination 5'UTR: HSD17B4 + 3'UTR: Gnas, more preferably the UTR-combination 5'UTR: Slc7a3 + 3'UTR: Gnas.

[0181] Each of the UTR elements defined in table 1 by reference to a specific SEQ ID NO may include variants or fragments of the nucleic acid sequence defined by said specific SEQ ID NO, exhibiting at least 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%, preferably of at least 70%, more preferably of at least 80%, even more preferably at least 85%, even more preferably of at least 90% and most preferably of at least 95% or even 97%, sequence identity to the respective nucleic acid sequence defined by reference to its specific SEQ ID NO. Each of the sequences identified in table 1 by reference to their specific SEQ ID NO may also be defined by its corresponding DNA sequence, as indicated herein. Each of the sequences identified in table 1 by reference to their specific SEQ ID NO may be modified (optionally independently from each other) as described herein below.

[0182] Preferred artificial nucleic acids according to the invention may comprise: a-1. at least one 5' UTR element derived from a 5'UTR of a HSD17B4 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR element derived from a 3'UTR of a PSMB3 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or a-2. at least one 5' UTR element derived from a 5'UTR of a NDUFA4 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR element derived from a 3'UTR of a PS B3 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or a-3. at least one 5' UTR element derived from a 5'UTR of a SLC7A3 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR element derived from a 3'UTR of a PSMB3 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or a-4. at least one 5' UTR element derived from a 5'UTR of a NOSIP gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR element derived from a 3'UTR of a PSMB3 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or a-5. at least one 5' UTR element derived from a 5'UTR of a MP68 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR element derived from a 3'UTR of a PSMB3 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or b-1. at least one 5' UTR element derived from a 5'UTR of a UBQLN2 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR element derived from a 3'UTR of a RPS9 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or b-2. at least one 5' UTR element derived from a 5'UTR of a ASAH1 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR element derived from a 3'UTR of a RPS9 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or b-3. at least one 5' UTR element derived from a 5'UTR of a HSD17B4 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR element derived from a 3'UTR of a RPS9 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or b-4. at least one 5' UTR element derived from a 5'UTR of a HSD17B4 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR element derived from a 3'UTR of a CASP1 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or b-5. at least one 5' UTR element derived from a 5'UTR of a NOSIP gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR element derived from a 3'UTR of a COX6B1 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or c-1. at least one 5' UTR element derived from a 5'UTR of a NDUFA4 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR element derived from a 3'UTR of a RPS9 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or c-2. at least one 5' UTR element derived from a 5'UTR of a NOSIP gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR element derived from a 3'UTR of a NDUFA1 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or c-3. at least one 5' UTR element derived from a 5'UTR of a NDUFA4 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR element derived from a 3'UTR of a COX6B1 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or c-4. at least one 5' UTR element derived from a 5'UTR of a NDUFA4 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR element derived from a 3'UTR of a NDUFA1 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or c-5. at least one 5' UTR element derived from a 5'UTR of a ATP5A1 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR element derived from a 3'UTR of a PSMB3 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or d-1. at least one 5' UTR element derived from a 5'UTR of a RPL31 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR element derived from a 3'UTR of a PSMB3 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or d-2. at least one 5' UTR element derived from a 5'UTR of a ATP5A1 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR element derived from a 3'UTR of a CASP1 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or d-3. at least one 5' UTR element derived from a 5'UTR of a SLC7A3 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR element derived from a 3'UTR of a GNAS1 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or d-4. at least one 5' UTR element derived from a 5'UTR of a HSD17B4 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR element derived from a 3'UTR of a NDUFA1 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or d-5. at least one 5' UTR element derived from a 5'UTR of a SLC7A3 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR element derived from a 3'UTR of a NDUFA1 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or e-1. at least one 5' UTR element derived from a 5'UTR of a TUBB4B gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR element derived from a 3'UTR of a RPS9 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or e-2. at least one 5' UTR element derived from a 5'UTR of a RPL31 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR element derived from a 3'UTR of a RPS9 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or e-3. at least one 5' UTR element derived from a 5'UTR of a MP68 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR element derived from a 3'UTR of a RPS9 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or e-4. at least one 5' UTR element derived from a 5'UTR of a NOSIP gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR element derived from a 3'UTR of a RPS9 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or e-5. at least one 5' UTR element derived from a 5'UTR of a ATP5A1 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR element derived from a 3'UTR of a RPS9 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or e-6. at least one 5' UTR element derived from a 5'UTR of a ATP5A1 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR element derived from a 3'UTR of a COX6B1 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or f-1. at least one 5' UTR element derived from a 5'UTR of a ATP5A1 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR element derived from a 3'UTR of a GNAS gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or f-2. at least one 5' UTR element derived from a 5'UTR of a ATP5A1 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR element derived from a 3'UTR of a NDUFA1 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or f.3 at least one 5' UTR element derived from a 5'UTR of a HSD17B4 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR element derived from a 3'UTR of a COX6B1 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or f-4 at least one 5' UTR element derived from a 5'UTR of a HSD17B4 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR element derived from a 3'UTR of a GNAS1 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or f-5. at least one 5' UTR element derived from a 5'UTR of a MP68 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR element derived from a 3'UTR of a COX6B1 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or g-1. at least one 5' UTR element derived from a 5'UTR of a MP68 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR element derived from a 3'UTR of a NDUFAl gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or g-2. at least one 5' UTR element derived from a 5'UTR of a NDUFA4 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR element derived from a 3'UTR of a CASP1 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or g-3. at least one 5' UTR element derived from a 5'UTR of a NDUFA4 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR element derived from a 3'UTR of a GNAS gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or g-4 at least one 5' UTR element derived from a 5'UTR of a NOSIP gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR element derived from a 3'UTR of a CASP1 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or g-5 at least one 5' UTR element derived from a 5'UTR of a RPL31 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR element derived from a 3'UTR of a CASP1 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or h-1 at least one 5' UTR element derived from a 5'UTR of a RPL31 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR element derived from a 3'UTR of a COX6B1 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or h-2 at least one 5' UTR element derived from a 5'UTR of a RPL31 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR element derived from a 3'UTR of a GNAS gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or h-3 at least one 5' UTR element derived from a 5'UTR of a RPL31 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR element derived from a 3'UTR of a NDUFAl gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or h-4 at least one 5' UTR element derived from a 5'UTR of a SLC7A3 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR element derived from a 3'UTR of a CASP1 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or h-5 at least one 5' UTR element derived from a 5'UTR of a SLC7A3 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR element derived from a 3'UTR of a COX6B1 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or i-1 at least one 5' UTR element derived from a 5'UTR of a SLC7A3 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR element derived from a 3'UTR of a RPS9 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or i-2 at least one 5' UTR element derived from a 5'UTR of a Ndufa4.1 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR element derived from a 3'UTR of a CASP1 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof.

[0183] Particularly preferred artificial nucleic acids may comprise a combination of UTRs according to a-1, a-2, a-3, a-4 or a-5, preferably according to a-1.

[0184] Surprisingly it was discovered that certain combinations of 5' and 3'-untranslated regions (UTRs) as disclosed herein act in concert to synergistically enhance the expression of operably linked nucleic acid sequences. Testing for synergy of UTR combinations is routine for a skilled person in the art, f.e. a test for synergy can be performed by Luciferase expression after mRNA transfection to prove that effects of synergy are present, i.e. more than an additive effect.

[0185] Expression i n the l iver

[0186] Any of the UTR combinations disclosed herein is envisaged to modulate, preferably induce and more preferably enhance, the expression of an operably linked coding sequence (cds). Without wishing to be bound by specific theory, some of the UTR combinations disclosed herein may be particularly useful when used in connection with specific coding sequences and / or when used in connection with a specific target cells or tissues.

[0187] In some embodiments, the artificial nucleic acid molecule according to the invention may comprise UTR elements according to a-2 (NDUFA4 / PSMB3); a-5 (MP68 / PSMB3); c-1 (NDUFA4 / RPS9); a-1 (HSD17B4 / PSMB3); e-3 (MP68 / RPS9); e-4 ( NOSIP / RPS9); a-4 ( NOSIP / PSMB3); e-2 (RPL31 / RPS9); e-5 (ATP5A1 / RPS9); d-4 (HSD17B4 / NUDFA1); b-5 ( NOSIP / COX6B1); a-3 (SLC7A3 / PSMB3); b-1 (UBQLN2 / RPS9); b-2 (ASAH1 / RPS9); b-4 (HSD17B4 / CASP1); e-6 (ATP5A1 / COX6B1); b-3 (HSD17B4 / RPS9); g-5 (RPL31 / CASP1); h-1 (RPL31 / COX6B1); and / or c-5 (ATP5A1 / PSMB3) as defined above. Such artificial nucleic acid molecules may be particularly useful for expression of an encoded (polypeptide or protein of interest in the liver. Accordingly, such artificial nucleic acid molecules are particularly envisaged for systemical administration, in particular intravenous, intraperitoneal, intramuscular or intratracheal administration or injection and optionally in combination with liver-targeting elements herein (as discussed below). Furthermore, without wishing to imply any particular limitation, the aforementioned UTR combinations may be particularly useful for artificial nucleic acids encoding, in their at least one coding region, a therapeutic (poly-)peptide or protein, an antigenic or allergic (poly-)peptide or protein as disclosed herein, for instance a protein useful in treating a disease selected from the group consisting of genetic diseases, allergies, autoimmune diseases, infectious diseases, neoplasms, cancer, and tumor-related diseases, inflammatory diseases, diseases of the blood and blood- forming organs, endocrine, nutritional and metabolic diseases, diseases of the nervous system, diseases of the circulatory system, diseases of the respiratory system, diseases of the digestive system, diseases of the skin and subcutaneous tissue, diseases of the musculoskeletal system and connective tissue, and diseases of the genitourinary system, independently if they are inherited or acquired, and combinations thereof. Dermis, epidermis a nd su bcuta neous expression

[0188] In some embodiments, the artificial nucleic acid molecule according to the invention may comprise UTR elements according to a-1 (HSD17B4 / PSMB3); a-3 (SLC7A3 / PS B3); e-2 (RPL31 / RPS9); a-5 (MP68 / PSMB3); d-1 (RPL31 / PSMB3); a-2 (NDUFA4 / PSMB3); h-1 (RPL31 / COX6B1); b-1 (UBQLN2 / RPS9); a-4 (NOSIP / PSMB3); c-5 (ATP5A1 / PS B3); b-5 (NOSIP / COX6B1); d-4 (HSD17B4 / NDUFAl); i-1 (SLC7A3 / RPS9); f-3 (HSD17B4 / COX6B1); b-4 (HSD17B4 / CASPl); g-5 (RPL31 / CASPl); c-2 (NOSIP / NDUFAl); e-4 (NOSIP / RPS9); c-4 (NDUFA4 / NDUFAl); and / or d-5 (SLC7A3 / NDUFAl) as defined above. Such artificial nucleic acid molecules may be particularly useful for expression of an encoded (poly-)peptide or protein of interest in the skin. Accordingly, such artificial nucleic acid molecules are particularly envisaged for intra-dermal administration, in particular topical, transdermal, intra-dermal injection, subcutaneous, or epicutaneous administration or injection herein. Furthermore, without wishing to imply any particular limitation, the aforementioned UTR combinations may be particularly useful for artificial nucleic acids encoding, in their at least one coding region, a therapeutic (poly-)peptide or protein, an antigenic or allergic (poly-)peptide or protein as disclosed herein, for instance a protein useful in treating a disease selected from the group consisting of genetic diseases, allergies, autoimmune diseases, infectious diseases, neoplasms, cancer, and tumor-related diseases, inflammatory diseases, diseases of the blood and blood- forming organs, endocrine, nutritional and metabolic diseases, diseases of the nervous system, diseases of the circulatory system, diseases of the respiratory system, diseases of the digestive system, diseases of the skin and subcutaneous tissue, diseases of the musculoskeletal system and connective tissue, and diseases of the genitourinary system, independently if they are inherited or acquired, and combinations thereof.

[0189] Expression in the m uscle

[0190] In some embodiments, the artificial nucleic acid molecule according to the invention may comprise UTR elements according to a-4 (NOSIP / PS B3); a-1 (HSD17B4 / PSMB3); a-5 (MP68 / PSMB3); d-3 (SLC7A3 / GNAS); a-2 (NDUFA4 / PSMB3); a-3 (SLC7A3 / PSMB3); d-5 (SLC7A3 / NDUFAl); i-1 (SLC7A3 / RPS9); d-1 (RPL31 / PS B3); d-4 (HSD17B4 / NDUFAl); b-3 (HSD17B4 / RPS9); f-3 (HSD17B4 / COX6B1); f-4 (HSD17B4 / GNAS); h-5 (SLC7A3 / COX6B1); g-4 (NOSIP / CASPl); c-3 (NDUFA4 / COX6B1); b-1 (UBQLN2 / RPS9); c-5 (ATP5A1 / PSMB3); h-4 (SLC7A3 / CASPl); h-2 (RPL31 / GNAS); e-1 (TUBB4B / RPS9); f-2 (ATP5A1 / NDUFAl); c-2 (NOSIP / NDUFAl); b-5 (NOSIP / COX6B1); and / or e-4 (NOSIP / RPS9) as defined above. Such artificial nucleic acid molecules may be particularly useful for expression of an encoded (poly-)peptide or protein of interest in the skeletal muscle, smooth muscle or cardiac muscle. Accordingly, such artificial nucleic acid molecules are particularly envisaged for intra-muscular administration, more preferably intra-muscular injection or intracardiac injection, herein. Furthermore, without wishing to imply any particular limitation, the aforementioned UTR combinations may be particularly useful for artificial nucleic acids encoding, in their at least one coding region, a therapeutic (poly-)peptide or protein, an antigenic or allergic (poly-)peptide or protein as disclosed herein, for instance a protein useful in treating a disease selected from the group consisting of genetic diseases, allergies, autoimmune diseases, infectious diseases, neoplasms, cancer, and tumor-related diseases, inflammatory diseases, diseases of the blood and blood- forming organs, endocrine, nutritional and metabolic diseases, diseases of the nervous system, diseases of the circulatory system, diseases of the respiratory system, diseases of the digestive system, diseases of the skin and subcutaneous tissue, diseases of the musculoskeletal system and connective tissue, and diseases of the genitourinary system, independently if they are inherited or acquired, and combinations thereof. Expression i n tu mo r a nd ca ncer cel ls

[0191] In some embodiments, the artificial nucleic acid molecule according to the invention may comprise UTR elements according to e-1 (TUBB4B / RPS9); b-2 (ASAH1 / RPS9); c-3 (NDUFA4 / COX6B1); a-1 (HSD17B4 / PS B3); c-4 (NDUFA4 / NDUFA1); b-4 (HSD17B4 / CASP1); d-2 (ATP5A1 / CASP1); b-5 (NOSIP / COX6B1); a-2 (NDUFA4 / PSMB3); b-1 (UBQLN / RPS9); a- 3 (SLC7A3 / PSMB3); f-4 (HSD17B4 / GNAS); c-2 (NOSIP / NDUFA1); b-3 (HSD17B4 / RPS9); c-5 (ATP5A1 / PSMB3); a-4 (NOSIP / PSMB3); d-5 (SLC7A3 / NDUFA1); or f-3 (HSD17B4 / COX6B1) as defined above. Such artificial nucleic acid molecules may be particularly useful for expression of an encoded (poly-)peptide or protein of interest in a tumor or cancer cell, including a carcinoma, sarcoma, lymphoma, leukemia, germ cell tumor or blastoma cell. Accordingly, such artificial nucleic acid molecules are particularly envisaged for intra-tumoral, intramuscular, subcutaneous, intravenous, intradermal, intraperitoneal, intrapleural, intraosseous administration or injection herein. Furthermore, without wishing to imply any particular limitation, the aforementioned UTR combinations may be particularly useful for artificial nucleic acids encoding, in their at least one coding region, a therapeutic (poly-)peptide or protein, an antigenic or allergic (poly-)peptide or protein as disclosed herein, for instance a protein useful in treating a disease selected from the group consisting of a cancer or tumor disease.

[0192] Expression in kid ney cel ls

[0193] In some embodiments, the artificial nucleic acid molecule according to the invention may comprise UTR elements according to b-2 (ASAH1 / RPS9); c-1 (NDUFA4 / RPS9.1); e-3 (MP68 / RPS9); c-4 (NDUFA4 / NDUFA1); c-2 (NOSIP / NDUFA1); h- 2 (RPL31 / CASP1); d-2 (ATP5A1 / CASP1); b-3 (HSD17B4 / RPS9); a-2 (NDUFA4 / PSMB3); f-4 (HSD17B4 / GNAS); d-3 (SLC7A3 / GNAS); g-1 ( P68 / NDUFA1); c-3 (NDUFA4 / COX6B1); e-5 (ATP5A1 / RPS9); h-3 (RPL31 / NDUFA1); a-1 (HSD17B4 / PSMB3); a-5 ( P68 / PS B3); g-4 (NOSIP / CASP1); b-1 (UQBLN / RPS9); d-4 (HSD17B4 / NDUFA1); or e-2 (RPL31 / RPS9) as defined above. Such artificial nucleic acid molecules may be particularly useful for expression of an encoded (poly-)peptide or protein of interest in kidney cells. Accordingly, such artificial nucleic acid molecules are particularly envisaged for systemical administration, in particular intravenous, intraperitoneal, intramuscular or intratracheal administration or injection and optionally in combination with kidney-targeting elements herein. Furthermore, without wishing to imply any particular limitation, the aforementioned UTR combinations may be particularly useful for artificial nucleic acids encoding, in their at least one coding region, a therapeutic (poly-)peptide or protein, an antigenic or allergic (poly-)peptide or protein as disclosed herein, for instance a protein useful in treating a disease selected from the group consisting of genetic diseases, allergies, autoimmune diseases, infectious diseases, neoplasms, cancer, and tumor- related diseases, inflammatory diseases, diseases of the blood and blood-forming organs, endocrine, nutritional and metabolic diseases, diseases of the nervous system, diseases of the circulatory system, diseases of the respiratory system, diseases of the digestive system, diseases of the skin and subcutaneous tissue, diseases of the musculoskeletal system and connective tissue, and diseases of the genitourinary system, independently if they are inherited or acquired, and combinations thereof.

[0194] In view of the above, artificial nucleic acid molecules according to the invention may be defined as indicated above, wherein said 5'UTR element derived from a HSD17B4 gene comprises or consists of a DNA sequence according to SEQ ID NO: 1 or a DNA sequence having, in increasing order of preference, at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% sequence identity to the nucleic acid sequence according to SEQ ID NO: 1, or a fragment or a variant thereof; or an RNA sequence according to SEQ ID NO: 2, or an RNA sequence having, in increasing order of preference, at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% sequence identity to the nucleic acid sequence according to SEQ ID NO: 2, or a fragment or a variant thereof; said 5'UTR element derived from a ASAH1 gene comprises or consists of a DNA sequence according to SEQ ID NO: 3 or a DNA sequence having, in increasing order of preference, at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% sequence identity to the nucleic acid sequence according to SEQ ID NO: 3, or a fragment or variant thereof; or an RNA sequence according to SEQ ID NO: 4, or an RNA sequence having, in increasing order of preference, at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% sequence identity to the nucleic acid sequence according to SEQ ID NO: 4, or a fragment or a variant thereof; said 5'UTR element derived from a ATP5A1 gene comprises or consists of a DNA sequence according to SEQ ID NO: 5, or a DNA sequence having, in increasing order of preference, at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% sequence identity to the nucleic acid sequence according to SEQ ID NO: 5, or a fragment or variant thereof; or an RNA sequence according to SEQ ID NO: 6, or an RNA sequence having, in increasing order of preference, at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% sequence identity to the nucleic acid sequence according to SEQ ID NO: 6, or a fragment or a variant thereof; said 5'UTR element derived from a MP68 gene comprises or consists of a DNA sequence according to SEQ ID NO: 7, or a DNA sequence having, in increasing order of preference, at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% sequence identity to the nucleic acid sequence according to SEQ ID NO: 7, or a fragment or variant thereof; or an RNA sequence according to SEQ ID NO: 8, or an RNA sequence having, in increasing order of preference, at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% sequence identity to the nucleic acid sequence according to SEQ ID NO: 8, or a fragment or a variant thereof; said 5'UTR element derived from a NDUFA4 gene comprises or consists of a DNA sequence according to SEQ ID NO: 9, or a DNA sequence having, in increasing order of preference, at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% sequence identity to the nucleic acid sequence according to SEQ ID NO: 9, or a fragment or variant thereof; or an RNA sequence according to SEQ ID NO: 10, or an RNA sequence having, in increasing order of preference, at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% sequence identity to the nucleic acid sequence according to SEQ ID NO: 10, or a fragment or a variant thereof; said 5'UTR element derived from a NOSIP gene comprises or consists of a DNA sequence according to SEQ ID NO: 11, or a DNA sequence having, in increasing order of preference, at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% sequence identity to the nucleic acid sequence according to SEQ ID NO: 11, or a fragment or variant thereof; or an RNA sequence according to SEQ ID NO: 12, or an RNA sequence having, in increasing order of preference, at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% sequence identity to the nucleic acid sequence according to SEQ ID NO: 12, or a fragment or a variant thereof; said 5'UTR element derived from a RPL31 gene comprises or consists of a DNA sequence according to SEQ ID NO: 13, or a DNA sequence having, in increasing order of preference, at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% sequence identity to the nucleic acid sequence according to SEQ ID NO: 13, or a fragment or variant thereof; an RNA sequence according to SEQ ID NO: 14, or an RNA sequence having, in increasing order of preference, at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% sequence identity to the nucleic acid sequence according to SEQ ID NO: 14, or a fragment or a variant thereof; said 5'UTR element derived from a SLC7A3 gene comprises or consists of a DNA sequence according to SEQ ID NO: 15, or a DNA sequence having, in increasing order of preference, at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% sequence identity to the nucleic acid sequence according to SEQ ID NO: 15, or a fragment or variant thereof; or an RNA sequence according to SEQ ID NO: 16, or an RNA sequence having, in increasing order of preference, at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% sequence identity to the nucleic acid sequence according to SEQ ID NO: 16, or a fragment or a variant thereof; said 5'UTR element derived from a TUBB4B gene comprises or consists of a DNA sequence according to SEQ ID NO: 17, or a DNA sequence having, in increasing order of preference, at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% sequence identity to the nucleic acid sequence according to SEQ ID NO: 17, or a fragment or variant thereof; or an RNA sequence according to SEQ ID NO: 18, or an RNA sequence having, in increasing order of preference, at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% sequence identity to the nucleic acid sequence according to SEQ ID NO: 18, or a fragment or a variant thereof; said 5'UTR element derived from a UBQLN2 gene comprises or consists of a DNA sequence according to SEQ ID NO: 19, or a DNA sequence having, in increasing order of preference, at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% sequence identity to the nucleic acid sequence according to SEQ ID NO: 19, or a fragment or variant thereof; or an RNA sequence according to SEQ ID NO: 20, or an RNA sequence having, in increasing order of preference, at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% sequence identity to the nucleic acid sequence according to SEQ ID NO: 20, or a fragment or a variant thereof; said 3'UTR element derived from a PSMB3 gene comprises or consists of a DNA sequence according to SEQ ID NO: 23, or a DNA sequence having, in increasing order of preference, at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% sequence identity to the nucleic acid sequence according to SEQ ID NO: 23, or a fragment or variant thereof; or an RNA sequence according to SEQ ID NO: 24, or an RNA sequence having, in increasing order of preference, at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% sequence identity to the nucleic acid sequence according to SEQ ID NO: 24, or a fragment or a variant thereof; said 3'UTR element derived from a CASP1 gene comprises or consists of a DNA sequence according to SEQ ID NO: 25, or a DNA sequence having, in increasing order of preference, at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% sequence identity to the nucleic acid sequence according to SEQ ID NO: 25, or a fragment or variant thereof; or an RNA sequence according to SEQ ID NO: 26, or an RNA sequence having, in increasing order of preference, at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% sequence identity to the nucleic acid sequence according to SEQ ID NO: 26, or a fragment or a variant thereof; said 3'UTR element derived from a COX6B1 gene comprises or consists of a DNA sequence according to SEQ ID NO: 27, or a DNA sequence having, in increasing order of preference, at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% sequence identity to the nucleic acid sequence according to SEQ ID NO: 27, or a fragment or variant thereof; or an RNA sequence according to SEQ ID NO: 28, or an RNA sequence having, in increasing order of preference, at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% sequence identity to the nucleic acid sequence according to SEQ ID NO: 28, or a fragment or a variant thereof; said 3'UTR element derived from a GNAS gene comprises or consists of a DNA sequence according to SEQ ID NO: 29, or a DNA sequence having, in increasing order of preference, at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% sequence identity to the nucleic acid sequence according to SEQ ID NO: 29, or a fragment or variant thereof; or an RNA sequence according to SEQ ID NO: 30, or an RNA sequence having, in increasing order of preference, at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% sequence identity to the nucleic acid sequence according to SEQ ID NO: 30, or a fragment or a variant thereof; said 3'UTR element derived from a NDUFA1 gene comprises or consists of a DNA sequence according to SEQ ID NO: 31, or a DNA sequence having, in increasing order of preference, at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% sequence identity to the nucleic acid sequence according to SEQ ID NO: 31, or a fragment or variant thereof; or an RNA sequence according to SEQ ID NO: 32, or an RNA sequence having, in increasing order of preference, at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% sequence identity to the nucleic acid sequence according to SEQ ID NO: 32, or a fragment or a variant thereof; and / or said 3'UTR element derived from a RPS9 gene comprises or consists of a DNA sequence according to SEQ ID NO: 33, or a DNA sequence having, in increasing order of preference, at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% sequence identity to the nucleic acid sequence according to SEQ ID NO: 33, or a fragment or variant thereof; or an RNA sequence according to SEQ ID NO: 34, or an RNA sequence having, in increasing order of preference, at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% sequence identity to the nucleic acid sequence according to SEQ ID NO: 34, or a fragment or a variant thereof.

[0195] Coding region

[0196] The artificial nucleic acid according to the invention comprises at least one coding region or coding sequence operably linked to -and typically flanked by- at least one 3'-UTR element and at least one 5'-UTR element as defined herein. The terms "coding sequence" or "cds" and "coding region" are used interchangeably herein to refer to a segment or portion of a nucleic acid that encodes a (gene) product of interest. Gene products are products of gene expression and include (poly-)peptides and nucleic acids, such as (protein-)coding RNAs (such as mRNAs) and non-(protein-)coding RNAs (such as tRNAs, rRNAs, microRNAs, siRNAs). Typically, the at least one coding region of the inventive artificial nucleic acid molecule may encode at least one (poly-)peptide or protein, hereinafter referred to as "(poly-)peptide or protein of interest". Coding regions may typically be composed of exons bounded by a start codon (such as AUG) at their 5'-end and a stop codon (such as UAG, UAA or UGA) at their 3' end. In the artificial nucleic acid molecules of the invention, the coding region is bounded by at least one 5'-UTR element and at least one 3'-UTR element as defined herein.

[0197] (Poly-)peptides or proteins of interest generally include any (poly-)peptide or protein that can be encoded by the nucleic acid sequence of the at least one coding region, and can be expressed under suitable conditions to yield a functional (poly-)peptide or protein product. In this context, the term "functional" means "capable of exerting a desired biological function" and / or "exhibiting a desired biological property". (Poly-)peptides or proteins of interest can have various functions and include, for instance, antibodies, enzymes, signaling proteins, receptors, receptor ligands, peptide hormones, transport proteins, structural proteins, neurotransmitters, growth regulating factors, serum proteins, carriers, drugs, immunomodulators, oncogenes, tumor suppressors, toxins, tumor antigens, and others. These proteins can be post- translationaliy modified to be proteins, glycoproteins, lipoproteins, phosphoproteins, etc. Further, the invention envisages any of the disclosed (poly-)peptides or proteins in their naturally occurring (wild-type) form, as well as variants, fragments and derivatives thereof. The encoded (poly-)peptides and proteins may have different effects. Without being limited thereto, coding regions encoding therapeutic, antigenic and allergenic (poly-)peptides are particularly envisaged herein.

[0198] Therapeutic (poly-)peptides or proteins

[0199] The at least one coding region of the artificial nucleic acid molecule of the invention may encode at least one "therapeutic (poly-)peptide or protein". The term "therapeutic (poly-)peptide or protein" refers to a (poly-)peptide or protein capable of mediating a desired diagnostic, prophylactic or therapeutic effect, preferably resulting in detection, prevention, amelioration and / or healing of a disease.

[0200] Preferably, artificial nucleic acid molecules according to the invention may comprise at least one coding region encoding a therapeutic protein replacing an absent, deficient or mutated protein; a therapeutic protein beneficial for treating inherited or acquired diseases; infectious diseases, or neoplasms e.g. cancer or tumor diseases); an adjuvant or immuno-stimulating therapeutic protein; a therapeutic antibody or an antibody fragment, variant or derivative; a peptide hormone; a gene editing agent; an immune checkpoint inhibitor; a T cell receptor, or a fragment, variant or derivative T cell receptor; and / or an enzyme.

[0201] "Therapeutic (poly-)peptides or proteins "replacing an absent, deficient or mutated protein" may be selected from any (poly-)peptide or protein exhibiting the desired biological properties and / or capable of exerting the desired biological function of a wild-type protein, whose absence, deficiency or mutation causes disease. Herein, "absent" means that protein expression from its encoding gene is prevented or abolished, typically to an extent that the protein is not detectable at its target site (i.e. cellular compartment, cell type, tissue or organ) in the affected subject's body. Protein expression can be affected at a variety of levels, and the "absence" or "lack of production" of a protein in an affected patient's body may be due to mutations in the encoding gene, e.g. epigenetic alterations or sequence mutations either its open reading frame or its regulatory elements (e.g. nonsense mutations or deletions leading to the hindrance or abrogation of gene transcription), defective mRNA processing (e.g. defective mRNA splicing, maturation or export from the nucleus), protein translation deficiencies, or errors in the protein folding, translocation (i.e. failure to correctly enter the secretory pathway) or transport (i.e. failure to correctly enter its destined export pathway) process. A protein "deficiency", i.e. reduced amount of protein detectable at its target site (i.e. cellular compartment, cell type, tissue or organ) in the affected subject's body, may be caused by the same mechanisms accounting for complete lack of protein expression as exemplified above. However, the defects leading to a protein "deficiency" may not always completely prevent or abolish protein expression from the affected gene, but rather lead to reduced expression levels (e.g. in cases where one allele is affected, and the other one functions normally). The term "mutated" encompasses both amino acid sequence variants and differences in the post-translational modification of proteins. Protein "mutants" may typically be non-functional, or mis-functional and may exhibit aberrant folding, translocation or transport properties or profiles.

[0202] Therapeutic (poly-)peptides or proteins "beneficial for treating inherited or acquired diseases such as infectious diseases, or neoplasms e.g. cancer or tumor diseases, diseases of the blood and blood-forming organs, endocrine, nutritional and metabolic diseases, diseases of the nervous system, diseases of the circulatory system, diseases of the respiratory system, diseases of the digestive system, diseases of the skin and subcutaneous tissue, diseases of the musculoskeletal system and connective tissue, and diseases of the genitourinary system, irrespective of being inherited or acquired" include any (poly-)peptides or protein whose expression is capable of preventing, ameliorating, or healing an inherited or acquired diseases. Such (poly-)peptides or proteins may in principle exert their therapeutic function by exerting any suitable biological action or function. In some embodiments, such (poly-)peptides or proteins may preferably not act by replacing an absent, deficient or mutated protein and / or by inducing an immune or allergenic response. For instance, (poly-)peptides or proteins beneficial for treating inherited or acquired diseases such as infectious diseases, or neoplasms may include particularly preferred therapeutic proteins which are inter alia beneficial in the treatment of acquired or inherited metabolic or endocrine disorders selected from (in brackets the particular disease for which the therapeutic protein is used in the treatment): Acid sphingomyelinase (Niemann-Pick disease), Adipotide (obesity), Agalsidase-beta (human galactosidase A) (Fabry disease; prevents accumulation of lipids that could lead to renal and cardiovascular complications), Alglucosidase (Pompe disease (glycogen storage disease type II)), alpha-galactosidase A (alpha-GAL A, Agalsidase alpha) (Fabry disease), alpha-glucosidase (Glycogen storage disease (GSD), Morbus Pompe), alpha-L-iduronidase (mucopolysaccharidoses (MPS), Hurler syndrome, Scheie syndrome), alpha-N-acetylglucosaminidase (Sanfilippo syndrome), Amphiregulin (cancer, metabolic disorder), Angiopoietin ((Angl, Ang2, Ang3, Ang4, ANGPTL2, ANGPTL3, ANGPTL4, ANGPTL5, ANGPTL6, ANGPTL7) (angiogenesis, stabilize vessels), Betacellulin (metabolic disorder), Beta- glucuronidase (Sly syndrome), Bone morphogenetic protein BMPs (BMP1, BMP2, BMP3, BMP4, BMP5, BMP6, BMP7, BMP8a, BMP8b, BMP10, BMP15) (regenerative effect, bone-related conditions, chronic kidney disease (CKD)), CLN6 protein (CLN6 disease - Atypical Late Infantile, Late Onset variant, Early Juvenile, Neuronal Ceroid Lipofuscinoses (NCL)), Epidermal growth factor (EGF) (wound healing, regulation of cell growth, proliferation, and differentiation), Epigen (metabolic disorder), Epiregulin (metabolic disorder), Fibroblast Growth Factor (FGF, FGF-1, FGF-2, FGF-3, FGF-4, FGF-5, FGF-6, FGF- 7, FGF-8, FGF-9, FGF-10, FGF-11, FGF-12, FGF-13, FGF-14, FGF-16, FGF-17, FGF-17, FGF-18, FGF-19, FGF-20, FGF-21, FGF-22, FGF-23) (wound healing, angiogenesis, endocrine disorders, tissue regeneration), Galsulphase (Mucopolysaccharidosis VI), Ghrelin (irritable bowel syndrome (IBS), obesity, Prader-Willi syndrome, type II diabetes mellitus), Glucocerebrosidase (Gaucher's disease), GM-CSF (regenerative effect, production of white blood cells, cancer), Heparin-binding EGF-like growth factor (HB-EGF) (wound healing, cardiac hypertrophy and heart development and function), Hepatocyte growth factor HGF (regenerative effect, wound healing), Hepcidin (iron metabolism disorders, Beta- thalassemia), Human albumin (Decreased production of albumin (hypoproteinaemia), increased loss of albumin (nephrotic syndrome), hypovolaemia, hyperbilirubinaemia), Idursulphase (Iduronate-2-sulphatase) (Mucopolysaccharidosis II (Hunter syndrome)), Integrins alphaVbeta3, alphaVbeta5 and alpha5betal (Bind matrix macromolecules and proteinases, angiogenesis), Iuduronate sulfatase (Hunter syndrome), Laronidase (Hurler and Hurler-Scheie forms of mucopolysaccharidosis I), N-acetylgalactosamine-4-sulfatase (rhASB; galsulfase, Arylsulfatase A (ARSA), Arylsulfatase B (ARSB)) (arylsulfatase B deficiency, Maroteaux-Lamy syndrome, mucopolysaccharidosis VI), N-acetylglucosamine-6- sulfatase (Sanfilippo syndrome), Nerve growth factor (NGF, Brain-Derived Neurotrophic Factor (BDNF), Neurotrophin-3 (NT-3), and Neurotrophin 4 / 5 (NT-4 / 5) (regenerative effect, cardiovascular diseases, coronary atherosclerosis, obesity, type 2 diabetes, metabolic syndrome, acute coronary syndromes, dementia, depression, schizophrenia, autism, Rett syndrome, anorexia nervosa, bulimia nervosa, wound healing, skin ulcers, corneal ulcers, Alzheimer's disease), Neuregulin (NRG1, NRG2, NRG3, NRG4) (metabolic disorder, schizophrenia), Neuropilin (NRP-1, NRP-2) (angiogenesis, axon guidance, cell survival, migration), Obestatin (irritable bowel syndrome (IBS), obesity, Prader-Willi syndrome, type II diabetes mellitus), Platelet Derived Growth factor (PDGF (PDFF-A, PDGF-B, PDGF-C, PDGF-D) (regenerative effect, wound healing, disorder in angiogenesis, Arteriosclerosis, Fibrosis, cancer), TGF beta receptors (endoglin, TGF-beta 1 receptor, TGF-beta 2 receptor, TGF-beta 3 receptor) (renal fibrosis, kidney disease, diabetes, ultimately end-stage renal disease (ESRD), angiogenesis), Thrombopoietin (THPO) (Megakaryocyte growth and development factor (MGDF)) (platelets disorders, platelets for donation, recovery of platelet counts after myelosuppressive chemotherapy), Transforming Growth factor (TGF (TGF-a, TGF-beta (TGFbetal, TGFbeta2, and TGFbeta3))) (regenerative effect, wound healing, immunity, cancer, heart disease, diabetes, Marfan syndrome, Loeys-Dietz syndrome), VEGF (VEGF-A, VEGF-B, VEGF-C, VEGF-D, VEGF-E, VEGF-F und PIGF) (regenerative effect, angiogenesis, wound healing, cancer, permeability), Nesiritide (Acute decompensated congestive heart failure), Trypsin (Decubitus ulcer, varicose ulcer, debridement of eschar, dehiscent wound, sunburn, meconium ileus), adrenocorticotrophic hormone (ACTH) ("Addison's disease, Small cell carcinoma, Adrenoleukodystrophy, Congenital adrenal hyperplasia, Cushing's syndrome, Nelson's syndrome, Infantile spasms), Atrial- natriuretic peptide (ANP) (endocrine disorders), Cholecystokinin (diverse), Gastrin (hypogastrinemia), Leptin (Diabetes, hypertriglyceridemia, obesity), Oxytocin (stimulate breastfeeding, non-progression of parturition), Somatostatin (symptomatic treatment of carcinoid syndrome, acute variceal bleeding, and acromegaly, polycystic diseases of the liver and kidney, acromegaly and symptoms caused by neuroendocrine tumors), Vasopressin (antidiuretic hormone) (diabetes insipidus), Calcitonin (Postmenopausal osteoporosis, Hypercalcaemia, Paget's disease, Bone metastases, Phantom limb pain, Spinal Stenosis), Exenatide (Type 2 diabetes resistant to treatment with metformin and a sulphonylurea), Growth hormone (GH), somatotropin (Growth failure due to GH deficiency or chronic renal insufficiency, Prader-Willi syndrome, Turner syndrome, AIDS wasting or cachexia with antiviral therapy), Insulin (Diabetes mellitus, diabetic ketoacidosis, hyperkalaemia), Insulin-like growth factor 1 IGF-1 (Growth failure in children with GH gene deletion or severe primary IGF1 deficiency, neurodegenerative disease, cardiovascular diseases, heart failure), Mecasermin rinfabate, IGF-1 analog (Growth failure in children with GH gene deletion or severe primary IGF1 deficiency, neurodegenerative disease, cardiovascular diseases, heart failure), Mecasermin, IGF-1 analog (Growth failure in children with GH gene deletion or severe primary IGF1 deficiency, neurodegenerative disease, cardiovascular diseases, heart failure), Pegvisomant (Acromegaly), Pramlintide (Diabetes mellitus, in combination with insulin), Teriparatide (human parathyroid hormone residues 1-34) (Severe osteoporosis), Becaplermin (Debridement adjunct for diabetic ulcers), Dibotermin-alpha (Bone morphogenetic protein 2) (Spinal fusion surgery, bone injury repair), Histrelin acetate (gonadotropin releasing hormone; GnRH) (Precocious puberty), Octreotide (Acromegaly, symptomatic relief of VIP-secreting adenoma and metastatic carcinoid tumours), and Palifermin (keratinocyte growth factor; KGF) (Severe oral mucositis in patients undergoing chemotherapy, wound healing), or an isoform, homolog, fragment, variant or derivative of any of these proteins.

[0203] These and other proteins are understood to be therapeutic, as they are meant to treat the subject by replacing its defective endogenous production of a functional protein in sufficient amounts.

[0204] Accordingly, such therapeutic proteins are typically mammalian, in particular human proteins.

[0205] For the treatment of acquired or inherited blood disorders, diseases of the circulatory system, diseases of the respiratory system, cancer or tumour diseases, infectious diseases or immunedeficiencies, the following therapeutic proteins may be used (in brackets is the particular disease for which a use of the therapeutic protein is indicated for treatment): Alteplase (tissue plasminogen activator; tPA) (Pulmonary embolism, myocardial infarction, acute ischaemic stroke, occlusion of central venous access devices), Anistreplase (Thrombolysis), Antithrombin III (AT-III) (Hereditary AT-III deficiency, Thromboembolism), Bivalirudin (Reduce blood-clotting risk in coronary angioplasty and heparin-induced thrombocytopaenia), Darbepoetin-alpha (Treatment of anaemia in patients with chronic renal insufficiency and chronic renal failure (+ / - dialysis)), Drotrecogin-alpha (activated protein C) (Severe sepsis with a high risk of death), Erythropoietin, Epoetin-alpha, erythropoetin, erthropoyetin (Anaemia of chronic disease, myleodysplasia, anaemia due to renal failure or chemotherapy, preoperative preparation), Factor IX (Haemophilia B), Factor Vila (Haemorrhage in patients with haemophilia A or B and inhibitors to factor VIII or factor IX), Factor VIII (Haemophilia A), Lepirudin (Heparin-induced thrombocytopaenia), Protein C concentrate (Venous thrombosis, Purpura fulminans), Reteplase (deletion mutein of tPA) (Management of acute myocardial infarction, improvement of ventricular function), Streptokinase (Acute evolving transmural myocardial infarction, pulmonary embolism, deep vein thrombosis, arterial thrombosis or embolism, occlusion of arteriovenous cannula), Tenecteplase (Acute myocardial infarction), Urokinase (Pulmonary embolism), Angiostatin (Cancer), Anti-CD22 immunotoxin (Relapsed CD33+ acute myeloid leukaemia), Denileukin diftitox (Cutaneous T-cell lymphoma (CTCL)), Immunocyanin (bladder and prostate cancer), MPS (Metallopanstimulin) (Cancer), Aflibercept (Non- small cell lung cancer (NSCLC), metastatic colorectal cancer (mCRC), hormone-refractory metastatic prostate cancer, wet macular degeneration), Endostatin (Cancer, inflammatory diseases like rheumatoid arthritis as well as Crohn's disease, diabetic retinopathy, psoriasis, and endometriosis), Collagenase (Debridement of chronic dermal ulcers and severely burned areas, Dupuytren's contracture, Peyronie's disease), Human deoxy-ribonuclease I, dornase (Cystic fibrosis; decreases respiratory tract infections in selected patients with FVC greater than 40% of predicted), Hyaluronidase (Used as an adjuvant to increase the absorption and dispersion of injected drugs, particularly anaesthetics in ophthalmic surgery and certain imaging agents), Papain (Debridement of necrotic tissue or liquefication of slough in acute and chronic lesions, such as pressure ulcers, varicose and diabetic ulcers, burns, postoperative wounds, pilonidal cyst wounds, carbuncles, and other wounds), L-Asparaginase (Acute lymphocytic leukaemia, which requires exogenous asparagine for proliferation), Peg-asparaginase (Acute lymphocytic leukaemia, which requires exogenous asparagine for proliferation), Rasburicase (Paediatric patients with leukaemia, lymphoma, and solid tumours who are undergoing anticancer therapy that may cause tumour lysis syndrome), Human chorionic gonadotropin (HCG) (Assisted reproduction), Human follicle-stimulating hormone (FSH) (Assisted reproduction), Lutropin-alpha (Infertility with luteinizing hormone deficiency), Prolactin (Hypoprolactinemia, serum prolactin deficiency, ovarian dysfunction in women, anxiety, arteriogenic erectile dysfunction, premature ejaculation, oligozoospermia, asthenospermia, hypofunction of seminal vesicles, hypoandrogenism in men), alpha-l-Proteinase inhibitor (Congenital antitrypsin deficiency), Lactase (Gas, bloating, cramps and diarrhoea due to inability to digest lactose), Pancreatic enzymes (lipase, amylase, protease) (Cystic fibrosis, chronic pancreatitis, pancreatic insufficiency, post-Billroth II gastric bypass surgery, pancreatic duct obstruction, steatorrhoea, poor digestion, gas, bloating), Adenosine deaminase (pegademase bovine, PEG-ADA) (Severe combined immunodeficiency disease due to adenosine deaminase deficiency), Abatacept (Rheumatoid arthritis (especially when refractory to TNFa inhibition)), Alefacept (Plaque Psoriasis ), Anakinra (Rheumatoid arthritis), Etanercept (Rheumatoid arthritis, polyarticular-course juvenile rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, plaque psoriasis, ankylosing spondylitis), Interleukin-1 (IL-1) receptor antagonist, Anakinra (inflammation and cartilage degradation associated with rheumatoid arthritis), Thymulin (neurodegenerative diseases, rheumatism, anorexia nervosa), TNF-alpha antagonist (autoimmune disorders such as rheumatoid arthritis, ankylosing spondylitis, Crohn's disease, psoriasis, hidradenitis suppurativa, refractory asthma), Enfuvirtide (HIV-1 infection), and Thymosin alphal (Hepatitis B and C), or an isoform, homolog, fragment, variant or derivative of any of these proteins.

[0206] Further therapeutic (poly-)peptides or proteins may be selected from: 0ATL3, 0FC3, 0PA3, 0PD2, 4-1BBL, 5T4, 6Ckine, 707-AP, 9D7, A2M, AA, AAAS, AACT, AASS, ABAT, ABCA1, ABCA4, ABCB1, ABCB11, ABCB2, ABCB4, ABCB7, ABCC2, ABCC6, ABCC8, ABCD1, ABCD3, ABCG5, ABCG8, ABL1, ABO, ABR ACAA1, ACACA, ACADL, ACADM, ACADS, ACADVL, ACATl, ACCPN, ACE, ACHE, ACHM3, ACHM1, ACLS, ACPI, ACTAl, ACTC, ACTN4, ACVRL1, AD2, ADA, ADAMTS13, ADAMTS2, ADFN, ADH1B, ADH1C, ADLDH3A2, ADRB2, ADRB3, ADSL, AEZ, AFA, AFD1, AFP, AGA, AGL, AGMX2, AGPS, AGS1, AGT, AGTR1, AGXT, AH02, AHCY, AHDS, AHHR, AHSG, AIC, AIED, AIH2, AIH3, AIM-2, AIPL1, AIRE, A 1, ALAD, ALAS2, ALB, HPG1, ALDH2, ALDH3A2, ALDH4A1, ALDH5A1, ALDH1A1, ALDOA, ALDOB, ALMS1, ALPL, ALPP, ALS2, ALX4, AMACR, AMBP, AMCD, AMCDl, AMCN, AMELX, AMELY, AMGL, AMH, AMHR2, AMPD3, AMPDl, AMT, ANC, ANCR, ANKl, ANOPl, AOM, AP0A4, AP0C2, AP0C3, AP3B1, APC, aPKC, APOA2, APOA1, APOB, APOC3, APOC2, APOE, APOH, APP, APRT, APS1, AQP2, AR, ARAFl, ARGl, ARHGEF12, ARMET, ARSA, ARSB, ARSC2, ARSE, ART-4, ARTCl / m, ARTS, ARVDl, ARX, AS, ASAH, ASAT, ASD1, ASL, ASMD, ASMT, ASNS, ASPA, ASS, ASSP2, ASSP5, ASSP6, AT3, ATD, ATHS, ATM, ATP2A1, ATP2A2, ATP2C1, ATP6B1, ATP7A, ATP7B, ATP8B1, ATPSK2, ATRX, ATXN1, ATXN2, ATXN3, AUTS1, AVMD, AVP, AVPR2, AVSD1, AXINl, AXIN2, AZF2, B2M, B4GALT7, B7H4, BAGE, BAGE-1, BAX, BBS2, BBS3, BBS4, BCA225, BCAA, BCH, BCHE, BCKDHA, BCKDHB, BCL10, BCL2, BCL3, BCL5, BCL6, BCPM, BCR, BCR / ABL, BDC, BDE, BDMF, BDMR, BEST1, beta-Catenin / m, BF, BFHD, BFIC, BFLS, BFSP2, BGLAP,BGN, BHD, BHR1, BING-4, BIRC5, BJS, BLM, BLMH, BLNK, BMPR2, BPGM, BRAF, BRCAl, BRCAl / m, BRCA2, BRCA2 / m, BRCD2, BRCD1, BRDT, BSCL, BSCL2, BTAA, BTD, BTK, BUB1, BWS, BZX, C0L2A1, C0L6A1, C1NH, C1QA, C1QB, C1QG, CIS, C2, C3, C4A, C4B, C5, C6, C7, C7orf2, C8A, C8B, C9, CA125, CA15-3 / CA 27-29, CA195, CA19-9, CA72-4, CA2, CA242, CA50, CABYR, CACD, CACNA2D1, CACNA1A, CACNA1F, CACNA1S, CACNB2, CACNB4, CAGE, CA1, CALB3, CALCA, CALCR, CALM, CALR, CAM43, CAMEL, CAP-1, CAPN3, CARD15, CASP-5 / m, CASP-8, CASP-8 / m, CASR, CAT, CATM, CAV3, CB1, CBBM, CBS, CCA1, CCAL2, CCAL1, CCAT, CCL-1, CCL-11, CCL-12, CCL-13, CCL-14, CCL-15, CCL- 16, CCL-17, CCL-18, CCL-19, CCL-2, CCL-20, CCL-21, CCL-22, CCL-23, CCL-24, CCL-25, CCL-27, CCL-3, CCL-4, CCL-5, CCL- 7, CCL-8, CCM1, CCNB1, CCND1, CCO, CCR2, CCR5, CCT, CCV, CCZS, CD1, CD19, CD20, CD22, CD25, CD27, CD27L, cD3, CD30, CD30, CD30L, CD33, CD36, CD3E, CD3G, CD3Z, CD4, CD40, CD40L, CD44, CD44v, CD44v6, CD52, CD55, CD56, CD59, CD80, CD86, CDAN1, CDAN2, CDAN3, CDC27, CDC27 / m, CDC2L1, CDH1, CDK4, CDK4 / m, CDKN1C, CDKN2A, CDKN2A / m, CDKN1A, CDKN1C, CDL1, CDPD1, CDR1, CEA, CEACAM1, CEACAM5, CECR, CECR9, CEPA, CETP, CFNS, CFTR, CGF1, CHAC, CHED2, CHED1, CHEK2, CHM, CHML, CHR39C, CHRNA4, CHRNA1, CHRNB1, CHRNE, CHS, CHS1, CHST6, CHX10, CIAS1, CIDX, CKN1, CLA2, CLA3, CLAl, CLCA2, CLCN1, CLCN5, CLCNKB, CLDN16, CLP, CLN2, CLN3, CLN4, CLN5, CLN6, CLN8, C1QA, C1QB, C1QG, C1R, CLS, CMCWTD, CMDJ, CMD1A, CMD1B, CMH2, MH3, CMH6, CMKBR2, CMKBR5, C L28, CML66, CMM, CMT2B, CMT2D, CMT4A, CMT1A, CMTX2, CMTX3, C-MYC, CNA1, CND, CNGA3, CNGA1, CNGB3, CNSN, CNTF, COA-l / m, COCH, COD2, COD1, COH1, COL10A, COL2A2, COL11A2, COL17A1, COL1A1, COL1A2, COL2A1, COL3A1, COL4A3, COL4A4, COL4A5, COL4A6, COL5A1, COL5A2, COL6A1, COL6A2, COL6A3, COL7A1, COL8A2, COL9A2, COL9A3, COL11A1, COL1A2, COL23A1, COL1A1, COLQ, COMP, COMT, CORD5, CORD1, COX10, COX-2, CP, CPB2, CPO, CPP, CPS1, CPT2, CPT1A, CPX, CRAT, CRB1, CRBM, CREBBP, CRH, CRHBP, CRS, CRV, CRX, CRYAB, CRYBA1, CRYBB2, CRYGA, CRYGC, CRYGD, CSA, CSE, CSF1R, CSF2RA, CSF2RB, CSF3R, CSF1R, CST3, CSTB, CT, CT7, CT-9 / BRD6, CTAA1, CTACK, CTEN, CTH, CTHM, CTLA4, CTM, CTNNBl, CTNS, CTPA, CTSB, CTSC, CTSK, CTSL, CTS1, CUBN, CVD1, CX3CL1, CXCL1, CXCL10, CXCL11, CXCL12, CXCL13, CXCL16, CXCL2, CXCL3, CXCL4, CXCL5, CXCL6, CXCL7, CXCL8, CXCL9, CYB5, CYBA, CYBB, CYBB5, , CYFRA 21-1, CYLD, CYLD1, CYMD, CYP11B1, CYP11B2, CYP17, CYP17A1, CYP19, CYP19A1, CYP1A2, CYP1B1, CYP21A2, CYP27A1, CYP27B1, CYP2A6, CYP2C, CYP2C19, CYP2C9, CYP2D, CYP2D6, CYP2D7P1, CYP3A4, CYP7B1, CYPB1, CYP11B1, CYP1A1, CYP1B1, CYRAA, D40,DADI, DAM, DAM-10 / MAGE-B1, DAM-6 / MAGE-B2, DAX1, DAZ, DBA, DBH, DBI, DBT, DCC, DC-CK1, DCK, DCR, DCX, DDB 1, DDB2, DDIT3, DDU, DECR1, DEK-CAN, DEM, DES, DF,DFN2, DFN4, DFN6, DFNA4, DFNA5, DFNB5, DGCR, DHCR7, DHFR, DHOF, DHS, DIA1, DIAPH2, DIAPH1, DIH1, DIOl, DISCI, DKC1, DLAT, DLD, DLL3, DLX3, DMBT1, DMD, DM1, DMPK, DMWD, DNAI1, DNASE1, DNMT3B, DPEP1, DPYD, DPYS, DRD2, DRD4, DRPLA, DSCR1, DSG1, DSP, DSPP, DSS, DTDP2, DTR, DURS1, DWS, DYS, DYSF, DYT2, DYT3, DYT4, DYT2, DYT1, DYX1, EBAF, EBM, EBNA, EBP, EBR3, EBS1, ECA1, ECB2, ECE1, ECGF1, ECT, ED2, ED4, EDA, EDAR, ECA1, EDN3, EDNRB, EEC1, EEF1A1L14, EEGV1, EFEMP1, EFTUD2 / m, EGFR, EGFR / Herl, EGI, EGR2, EIF2AK3, eIF4G, EKV, El IS, ELA2, ELF2, ELF2M, ELK1, ELN, ELONG, EMD, EML1, EMMPRIN, EMX2, ENA-78, ENAM, END3, ENG, ENOl, ENPP1, ENUR2, ENUR1, EOS, EP300, EPB41, EPB42, EPCAM, EPD, EphAl, EphA2, EphA3, EphrinA2, EphrinA3, EPHX1, EPM2A, EPO,EPOR, EPX, ERBB2, ERCC2 ERCC3,ERCC4, ERCC5, ERCC6, ERVR, ESR1, ETFA, ETFB, ETFDH, ETM1, ETV6-AML1, ETV1, EVC, EVR2, EVR1, EWSR1, EXT2, EXT3, EXT1, EYA1, EYCL2, EYCL3, EYCL1, EZH2, F10, Fll, F12, F13A1, F13B, F2, F5, F5F8D, F7, F8, F8C, F9, FABP2, FACL6, FAH, FANCA, FANCB, FANCC, FANCD2, FANCF, FasL,FBN2, FBN1, FBP1, FCG3RA,FCGR2A, FCGR2B, FCGR3A, FCHL, FCMD, FCP1, FDPSL5, FECH, FEO, FEOM1, FES, FGA, FGB, FGD1, FGF2, FGF23, FGF5, FGFR2, FGFR3, FGFR1, FGG, FGS1, FH, FICl, FIH, F2, FKBP6, FLNA, FLT4, FM03,FM04, FMR2, FMR1, FN, FNl / m, FOXC1, FOXE1, FOXL2, FOX01A, FPDMM, FPF, Fra-1, FRAXF, FRDA, FSHB, FSHMD1A, FSHR, FTH1, FTHL17, FTL, FTZFl, FUCA1, FUT2, FUT6, FUT1, FY, G250, G250 / CAIX, G6PC, G6PD, G6PT1, G6PT2, GAA, GABRA3, GAGE-1, GAGE-2, GAGE-3, GAGE-4, GAGE-5, GAGE-6, GAGE-7b, GAGE-8, GALC, GALE, GALKl, GALNS, GALT, GAMT, GAN, GAST, GASTRIN17, GATA3, GATA, GBA, GBE, GC, GCDH, GCGR, GCHl, GCK, GCP-2, GCSl, G-CSF, GCSH, GCSL, GCY, GDEP,GDF5, GDIl, GDNF, GDXY, GFAP, GFND, GGCX, GGT1, GH2, GH1, GHR, GHRHR, GHS, GIF, GINGF, GIP, GJA3, GJA8, GJB2, GJB3, GJB6, GJB1, GK, GLA, GLB, GLB1, GLC3B, GLC1B, GLC1C, GLDC, GLI3, GLP1, GLRA1, GLUD1, GM1 (fuc-GMl), GM2A, GM-CSF, GMPR, GNAI2, GNAS, GNATl, GNB3, GNE, GNPTA, GNRH, GNRHl, GNRHR, GNS, GnT-V, gplOO, GPIBA, GPIBB, GP9, GPC3, GPD2, GPDSl, GPI, GPIBA, GPNILW, GPNMB / m, GPSC, GPXl, GRHPR, GRKl, GROa, GRG , GROy, GRPR, GSE, GSMl, GSN, GSR, GSS, GTD, GTS, GUCAIA, GUCY2D, GULOP, GUSB, GUSM, GUST, GYPA, GYPC, GYS1, GYS2, H0KPP2, H0MG2, HADHA, HADHB, HAGE, HAGH, HAL, HAST-2, HB 1, HBA2, HBA1, HBB, HBBP1, HBD, HBE1, HBG2, HBG1, HBHR, HBP1, HBQ1, HBZ, HBZP, HCA, HCC-1, HCC-4, HCF2, HCG, HCL2, HCL1, HCR, HCVS, HD, HPN, HER2, HER2 / NEU, HER3, HERV-K-MEL, HESX1, HEXA, HEXB, HF1, HFE, HF1, HGD, HHC2, HHC3, HHG, HK1 HLA-A, HLA-A*0201-R170I, HLA-All / m, HLA-A2 / m, HLA-DPB1 HLA-DRA, HLCS, HLXB9, HMBS, HMGA2, HMGCL, HMI, HMN2, HMOX1, HMS1 HMW-MAA, HND, HNE, HNF4A, HOAC, HOMEOBOX NKX 3.1, HOM-TES-14 / SCP-1, HOM-TES-85, HOXA1 HOXD13, HP, HPC1, HPD, HPE2, HPE1, HPFH, HPFH2, HPRT1, HPS1, HPT, HPV-E6, HPV-E7, HR, HRAS, HRD, HRG, HRPT2, HRPT1, HRX, HSD11B2, HSD17B3, HSD17B4, HSD3B2, HSD3B3, HSN1, HSP70-2M, HSPG2, HST-2, HTC2, HTC1, TERT, HTN3, HTR2C, HVBS6, HVBS1, HVEC, HV1S, HYAL1, HYR, 1-309, IAB, IBGC1, IBM2, ICAM1, ICAM3, iCE, ICHQ, ICR5, ICR1, ICS 1, IDDM2, IDDM1, IDS, IDUA, IF, IFNa / b, IFNGR1, IGAD1, IGER, IGF-1R, IGF2R, IGF1, IGH, IGHC, IGHG2, IGHG1, IGHM, IGHR, IGKC, IHG1, IHH, IKBKG, ILL, IL-1 RA, IL10, IL-11, IL12, IL12RB1, IL13, IL-13Ralpha2, IL-15, IL-16, IL-17, IL18, IL-la, IL-lalpha, IL-lb, IL-lbeta, IL1RAPL1, IL2, IL24, IL-2R, IL2RA, IL2RG, IL3, IL3RA,IL4, IL4R,IL4R, IL-5, IL6, IL-7, IL7R, IL-8, IL-9, Immature laminin receptor, IMMP2L, INDX, INFGR1, INFGR2, INFalpha, IFNbeta, INFgamma, INS, INSR, INVS, IP-10, IP2, IPF1, IP1, IRF6, IRS1, ISCW, ITGA2, ITGA2B, ITGA6, ITGA7, ITGB2, ITGB3, ITGB4, ITIH1, ITM2B, IV, IVD, JAG1, JAK3, JBS, JBTS1, JMS, JPD, KALI, KAL2, KALI, KLK2, KLK4, KCNA1, KCNE2, KCNE1, KCNH2, KCNJ1, KCNJ2, KCNJ1, KCNQ2, KCNQ3, KCNQ4, KCNQ1, KCS, KERA, KFM, KFS, KFSD, KHK, ki-67, KIAA0020, KIAA0205, KIAA0205 / m, KIF1B, KIT, KK-LC-1, KLK3, KLKB1, KM-HN-1, KMS, KNG, KNO, K-RAS / m, KRAS2, KREV1, KRT1, KRT10, KRT12, KRT13, KRT14, KRT14L1, KRT14L2, KRT14L3,KRT16, KRT16L1, KRT16L2, KRT17, KRT18, KRT2A, KRT3, KRT4, KRT5, KRT6 A, KRT6B, KRT9, KRTHB1, KRTHB6, KRT1, KSA, KSS, KWE, KYNU, L0H19CR1, L1CAM, LAGE, LAGE-1, LALL, LAMA2, LAMA3, LAMB3, LAMBl, LAMC2, LAMP2, LAP, LCA5, LCAT, LCCS, LCCS 1, LCFS2, LCS1, LCT, LDHA, LDHB, LDHC, LDLR, LDLR / FUT, LEP, LEWISY, LGCR, LGGF-PBP, LGI1, LGMD2H, LGMD1A, LGMD1B, LHB, LHCGR, LHON, LHRH, LHX3, LIF, LIG1, LIMM, UMP2, LIPA, LIPA, LIPB, LIPC, LIVIN, L1CAM, LMAN1, LMNA, LMX1B, LOLR, LOR, LOX, LPA, LPL, LPP, LQT4, LRP5, LRS 1, LSFC, LT-beta , LTBP2, LTC4S, LYL1, XCL1, LYZ, M344, MA50, MAA, MADH4, MAFD2, MAFD1, MAGE, MAGE-A1, MAGE-A10, MAGE-A12, MAGE-A2, MAGE-A3, MAGE-A4, MAGE-A6, MAGE-A9, MAGEB1, MAGE-BIO, MAGE-B16, MAGE-B17, MAGE-B2, MAGE-B3, MAGE-B4, MAGE-B5, MAGE-B6, MAGE-C1, MAGE-C2, MAGE-C3, MAGE-D1, MAGE-D2, MAGE-D4, MAGE-E1, MAGE-E2, MAGE-F1,MAGE-H1, MAGEL2, MGB1, MGB2, MAN2A1, MAN2B1, MANBA, MANBB, MAOA, MAOB, MAPK8IP1, MAPT, MART- 1, MART-2, MART2 / m, MAT1A, MBL2, MBP, MBS1, MC1R, MC2R, MC4R, MCC, MCCC2, MCCC1, MCDR1, MCF2, MCKD, MCL1, MC1R, MCOLN1, MCOP, MCOR, MCP-1, MCP-2, MCP-3, MCP-4, MCPH2, MCPH1, MCS, M-CSF, MDB, MDCR, MDM2, MDRV, MDS 1, ME1, MEl / m, ME2, ME20, ME3, MEAX, MEB, MEC CCL-28, MECP2, MEFV, MELANA, MELAS, MEN1 MSLN, MET, MF4, MG50, MG50 / PXDN, MGAT2, MGAT5, MGC1 MGCR, MGCT, MGI, MGP, MHC2TA, MHS2, MHS4, MIC2, MIC5, MIDI, MIF, MIP, MIP-5 / HCC-2, MITF, MJD, MKI67, MKKS, MKS1, MLH1, MLL, MLLT2, MLLT3, MLLT7, MLLT1, MLS, MLYCD, MMAla, MMP 11, MMVP1, M / CA IX-Antigen, MNG1, N1, M0C31, M0CS2, M0CS1, MOG, MORC, MOS, MOV18, MPD1, MPE, MPFD, MPI, MPIF-1, MPL, MPO, MPS3C, MPZ, MREllA, MROS, MRPl, MRP2, MRP3, MRSD, MRX14, MRX2, MRX20, MRX3, MRX40, MRXA, MRXl, MS, MS4A2, MSD, MSH2, MSH3, MSH6, MSS, MSSE, MSX2, MSX1, MTATP6, MTC03, MTCOl, MTCYB, MTHFR, MTMl, MTMR2, MTND2, MTND4, MTND5, MTND6, MTNDl, MTP, MTR, MTRNR2, MTRNRl, MTRR,MTTE, MTTG, MTTI, MTTK, MTTL2, MTTLl, MTTN, MTTP, MTTS1, MUC1,MUC2, MUC4, MUC5AC, MUM-1, MUM-l / m, MUM-2, MUM-2 / m, MUM-3, MUM-3 / m, MUT, mutant p21 ras, MUTYH, MVK, MX2, MXI1, MY05A, MYB, MYBPC3, MYC, MYCL2, MYH6, MYH7, MYL2, MYL3, MYMY, MY015A, MYOIG, MY05A, MY07A, MYOC, Myosin / m, MYP2, MYP1, NA88-A, N- acetylglucosaminyltransferase-V, NAGA, NAGLU, NAMSD, NAPB, NAT2, NAT, NBIA1, NBS1, NCAM, NCF2, NCF1, NDN , NDP, NDUFS4, NDUFS7, NDUFS8, NDUFV1, NDUFV2, NEB, NEFH, NEM1, Neo-PAP, neo-PAP / m, NEU1, NEUROD1, NF2, NF1, NFYC / m, NGEP, NHS, NKS1, N X2E, NM, NME1, NMP22, NMTC, NODAL, NOG, NOS3, NOTCH3, NOTCH1, NP, NPC2, NPC1, NPHL2, NPHP1, NPHS2, NPHS1, NPM / ALK, NPPA, NQOl, NR2E3, NR3C1, NR3C2, NRAS, NRAS / m, NRL, OB1, NRTN, NSE, NSX, NTRK1, NUMA1, NXF2, NY-COl, NY-ESOl, NY-ESO-B, NY-LU-12, ALDOA, NYS2, NYS4, NY-SAR-35, NYS1, NYX, OA3, OA1, OAP, OASD, OAT, OCA1, OCA2, OCD1, OCRL, OCRL1, OCT, ODDD, ODT1, OFC1, OFD1, OGDH, OGT, OGT / m, OPA2, OPA1, OPD1, OPEM, OPG, OPN, OPN1LW, OPN1MW, OPN1SW, OPPG, OPTB1, TTD, ORM1, ORP1, OS-9, OS-9 / m, OSM LIF, OTC, OTOF, OTSC1, OXCT1, OYTES1, P15, P190 MINOR BCR-ABL, P2RY12, P3, P16, P40, P4HB, P-501, P53, P53 / m, P97, PABPN1, PAFAH1B1, PAFAH1P1, PAGE-4, PAGE-5, PAH, PAI-1, PAI-2, PAK3, PAP, PAPPA, PARK2, PART-1, PATE, PAX2, PAX3, PAX6, PAX7, PAX8, PAX9, PBCA, PBCRA1, PBT, PBX1, PBXP1, PC, PCBD, PCCA, PCCB, PCK2, PCK1, PCLD, PCOS1, PCSKl, PDB1, PDCN, PDE6A, PDE6B, PDEF, PDGFB, PDGFR, PDGFRL, PDHA1, PDR, PDX1, PECAM1, PEE1, PEOl, PEPD, PEX10, PEX12, PEX13, PEX3, PEX5, PEX6, PEX7, PEX1, PF4, PFBI, PFC, PFKFB1, PFKM, PGAM2, PGD, PGK1, PGK1P1, PGL2, PGR, PGS, PHA2A, PHB, PHEX, PHGDH, PHKA2, PHKA1, PHKB, PHKG2, PHP, PHYH, PI, PI3, RIGA, PIM1-KINASE, PIN1, PIP5K1B, PITX2, ΡΓΓΧ3, PKD2, PKD3, PKD1, PKDTS, PKHD1, PKLR, PKP1, PKU1, PLA2G2A, PLA2G7, PLAT, PLEC1, PLG, PLI, PLOD, PLP1, PMEL17, PML, PML / RARalpha, PMM2, PMP22, PMS2, PMS1, PNKD, PNLIP, POF1, POLA, POLH, POMC, PON2, PON1, PORC, POTE, POU1F1, POU3F4, POU4F3, POU1F1, PPAC, PPARG, PPCD, PPGB, PPH1, PPKB, PPMX, PPOX, PPP1R3A, PPP2R2B, PPT1, PRAME, PRB, PRB3, PRCA1, PRCC, PRD, PRDX5 / m, PRF1, PRG4, PRKAR1A, PRKCA, PRKDC, PRKWNK4, PRNP, PROC, PRODH, PROM1, PROP1, PROS1, PRST, PRP8, PRPF31, PRPF8, PRPH2, PRPS2, PRPS1, PRS, PRSS7, PRSS1, PRTN3, PRX, PSA, PSAP, PSCA, PSEN2, PSEN1, PSG1, PSGR, PSM, PSMA, PSORS1, PTC, PTCH, PTCH1, PTCH2, PTEN, PTGS1, PTH, PTHR1, PTLAH, PTOS1, PTPN12, PTPNI I, PTPRK, PTPRK / m, PTS, PUJO, PVR, PVRL1, PWCR, PXE, PXMP3, PXR1, PYGL, PYGM, QDPR, RAB27A, RAD54B, RAD54L, RAG2, RAGE, RAGE-1, RAG1, RAP1, RARA, RASA1, RBAF600 / m, RBI, RBP4, RBP4, RBS, RCA1, RCAS1, RCCP2, RCD1, RCV1, RDH5, RDPA, RDS, RECQL2, RECQL3, RECQL4, REG1A, REHOBE, REN, RENBP, RENS1, RET, RFX5, RFXANK, RFXAP, RGR, RHAG, RHAMM / CD168, RHD, RHO, Rip-1, RLBP1, RLN2, RLN1, RLS, RMD1, RMRP, ROM1, ROR2, RP, RP1, RP14, RP17, RP2, RP6, RP9, RPD1, RPE65, RPGR, RPGRIP1, RP1, RP10, RPS19, RPS2, RPS4X, RPS4Y, RPS6KA3, RRAS2, RSI, RSN, RSS, RU1, RU2, RUNX2,RUNXI, RWS, RYR1, S-100, SAAl, SACS, SAG, SAGE, SALL1, SARDH, SART1, SART2 , SART3, SAS, SAX1, SCA2, SCA4, SCA5, SCA7, SCA8, SCA1, SCC, SCCD, SCF, SCLC1, SCN1A, SCN1B, SCN4A, SCN5A, SCNN1A, SCNN1B, SCNN1G, SC02, SCP1, SCZD2, SCZD3, SCZD4, SCZD6, SCZD1, SDF-lalpha / beta, SDHA, SDHD, SDYS, SEDL, SERPENA7, SERPINA3, SERPINA6, SERPINA1, SERPINC1, SERPIND1, SERPINE1, SERPINF2, SERPING1, SERPINI1, SFTPA1, SFTPB, SFTPC, SFTPD, SGCA, SGCB, SGCD, SGCE, SGMl, SGSH, SGY-1, SH2D1A, SHBG, SHFM2, SHFM3, SHFMl, SHH, SHOX, SI, SIAL, SIALYL LEWISX , SIASD, Sll, SIM1, SIRT2 / m, SIX3, SJS1, SKP2, SLC10A2, SLC12A1, SLC12A3, SLC17A5, SLC19A2, SLC22A1L, SLC22A5, SLC25A13, SLC25A15, SLC25A20, SLC25A4, SLC25A5, SLC25A6, SLC26A2, SLC26A3, SLC26A4, SLC2A1, SLC2A2, SLC2A4, SLC3A1, SLC4A1, SLC4A4, SLC5A1, SLC5A5, SLC6A2, SLC6A3, SLC6A4, SLC7A7, SLC7A9, SLC11A1, SLOS, SMA, SMAD1, SMAL, SMARCB1, SMAX2, SMCR, SMCY, SMI, SMN2, SMN1, SMPD1, SNCA, SNRPN, SOD2, SOD3, SOD1, SOS1, SOST, SOX9, SOX10, Spl7, SPANXC, SPG23, SPG3A, SPG4, SPG5A, SPG5B, SPG6, SPG7, SPINK1, SPINK5, SPPK, SPPM, SPSMA, SPTA1, SPTB, SPTLC1, SRC, SRD5A2, SRPX, SRS, SRY, BhCG, SSTR2, SSX1, SSX2 (HOM-MEL-40 / SSX2), SSX4, ST8, STAMP-1, STAR, STARP1, STATH, STEAP, STK2, STK11, STn / KLH, STO, STOM, STS, SUOX, SURF1, SURVIVIN-2B, SYCP1, SYM1, SYN1, SYNS1, SYP, SYT / SSX, SYT-SSX-1, SYT-SSX-2, TA-90, TAAL6, TACSTD1, TACSTD2, TAG72, TAF7L, TAF1, TAGE, TAG-72, TALI, TAM, TAP2, TAPl, TAPVRl, TARC, TARP, TAT, TAZ, TBP, TBX22, TBX3, TBX5, TBXA2R, TBXASl, TCAP, TCF2, TCFl, TCIRGl, TCL2, TCL4, TCLIA, TCN2, TCOFl, TCR, TCRA, TDD, TDFA, TDRDl, TECK, TECTA, TEK, TEL / AMLl, TELABl, TEX15, TF, TFAP2B, TFE3, TFR2, TG, TGFalpha, TGFbeta, TGFbetal, TGFbetal, TGFbetaR2, TGFbetaRE, TGFgamma, TGFbetaRII, TGIF, TGM-4, TGMl, TH, THAS, THBD, THC, THC2, THM, THPO, THRA, THRB, TIMM8A, TIMP2, TIMP3, TIMP1, TITF1, TKCR, TKT, TLP, TLR1, TLR10, TLR2, TLR3, TLR4, TLR4, TLR5, TLR6, TLR7, TLR8, TLR9, TLX1, TM4SF1, TM4SF2, TMC1, TMD, TMIP, TNDM, TNF, TNFRSF11A, TNFRSF1A, TNFRSF6, TNFSF5, TNFSF6, TNFalpha, TNFbeta, TNNI3, TNNT2, TOC, TOP2A, TOPI, TP53, TP63, TPA, TPBG, TPI, TPI / m, TPI1, TPM3, TPM1, TPMT, TPO, TPS, TPTA, TRA, TRAG3, TRAPPC2, TRC8, TREH, TRG, TRH, TRIM32, TRIM37, TRP1, TRP2, TRP-2 / 6b, TRP-2 / INT2, Trp-p8, TRPS1, TS, TSC2, TSC3, TSC1, TSG101, TSHB, TSHR, TSP-180, TST, TTGA2B, TTN, TTPA, TTR, TU M2-PK, TULP1, TWIST, TYH, TYR, TYROBP, TYROBP, TYRPl, TYS, UBE2A, UBE3A, UBE1, UCHL1, UFS, UGT1A, ULR, UMPK, UMPS, UOX, UPA, UQCRC1, UR05, UROD, UPK1B, UROS, USH2A, USH3A, USH1A, USH1C, USP9Y, UV24, VBCH, VCF, VDI, VDR, VEGF, VEGFR-2, VEGFR-1, VEGFR-2 / FLK-1, VHL, VIM, VMD2, VMD1, VMGLOM, VNEZ, VNF, VP, VRNI, VWF, VWS, WAS, WBS2, WFS2, WFS1, WHCR, WHN, WISP3, WMS, WRN, WS2A, WS2B, WSN, WSS, WT2, WT3, WTl, WTS, WWS, XAGE, XDH, XIC, XIST, XK, XM, XPA, XPC, XRCC9, XS, ZAP70, ZFHX1B, ZFX, ZFY, ZIC2, ZIC3, ZNF145, ZNF261, ZNF35, ZNF41, ZNF6, ZNF198, and ZWS1, or an isoform, homolog, fragment, variant or derivative of any of these proteins.

[0207] Further therapeutic (poly-)peptides or proteins may be selected from apoptotic factors or apoptosis related proteins including AIF, Apaf e.g. Apaf-1, Apaf-2, Apaf-3, oder APO-2 (L), APO-3 (L), Apopain, Bad, Bak, Bax, Bcl-2, Bel- x[L], Bcl- x[s], bik, CAD, Calpain, Caspase e.g. Caspase-1, Caspase-2, Caspase-3, Caspase-4, Caspase-5, Caspase-6, Caspase-7, Caspase-8, Caspase-9, Caspase-10, Caspase-1 1, ced-3, ced-9, c-Jun, c-Myc, crm A, cytochrom C, CdRl, DcRl, DD, DED, DISC, DNA-PKc[S], DR3, DR4, DR5, FADD / MORT-1, FAK, Fas (Fas-ligand CD95 / fas (receptor)), FLICE / MACH, FLIP, fodrin, fos, G-Actin, Gas-2, gelsolin, granzyme A / B, ICAD, ICE, JNK, lamin A / B, MAP, MCL-1, Mdm-2, MEKK-1, MORT-1, NEDD, NF-[kappa]B, NuMa, p53, PAK- 2, PARP, perforin, PITSLRE, PKCdelta, pRb, presenilin, prICE, RAIDD, Ras, RIP, sphingomyelinase, thymidinkinase from herpes simplex, TRADD, TRAF2, TRAIL-Rl, TRAIL-R2, TRAIL-R3, transglutaminase, et cetera, or an isoform, homolog, fragment, variant or derivative of any of these proteins.

[0208] An "adjuvant" (poly-)peptide or protein generally means any (poly-)peptide or protein capable of modifying the effect of other agents, typically other active agents that are administered simultaneously. Preferably, "adjuvant or immunostimulating" (poly-)peptides or proteins are capable potentiating or modulating a desired immune response to a (preferably co-administered) antigen. In particular, an "adjuvant or immuno-stimulating" (poly-)peptide or protein may act to accelerate, prolong, or enhance immune responses when used in combination with specific antigens. To that end, "adjuvant or immuno-stimulating" (poly-)peptides or proteins may support administration and delivery of co-administered antigens, enhance the (antigen-specific) immunostimulatory properties of co-administered antigens, and / or initiate or increase an immune response of the innate immune system, i.e. a non-specific immune response. Exemplary "adjuvant or immunostimulating (poly-)peptides or proteins" envisaged in the present invention include mammalian proteins, in particular human adjuvant proteins, which typically comprise any human protein or peptide, which is capable of eliciting an innate immune response (in a mammal), e.g. as a reaction of the binding of an exogenous TLR ligand to a TLR. More preferably, human adjuvant proteins are selected from the group consisting of proteins which are components and ligands of the signalling networks of the pattern recognition receptors including TLR, NLR and RLH, including TLR1, TLR2, TLR3, TLR4, TLR5, TLR6, TLR7, TLR8, TLR9, TLR10, TLRll; NODI, NOD2, NOD3, NOD4, NOD5, NALPl, NALP2, NALP3, NALP4, NALP5, NALP6, NALP6, NALP7, NALP7, NALP8, NALP9, NALP10, NALP11, NALP12, NALP13, NALP14,I IPAF, NAIP, CIITA, RIG-I, MDA5 and LGP2, the signal transducers of TLR signaling including adaptor proteins including e.g. Trif and Cardif; components of the Small-GTPases signalling (RhoA, Ras, Racl, Cdc42, Rab etc.), components of the PIP signalling (PI3K, Src-Kinases, etc.), components of the MyD88-dependent signalling (MyD88, IRAKI, I AK2, IRAK4, TIRAP, TRAF6 etc.), components of the MyD88-independent signalling (TICAM1, TICAM2, TRAF6, TBK1, IRF3, TAK1, IRAKI etc.); the activated kinases including e.g. Akt, MEKK1, MKK1, MKK3, MKK4, MKK6, MKK7, ERK1, ERK2, GSK3, PKC kinases, PKD kinases, GSK3 kinases, JNK, p38MAPK, TAK1, IKK, and TAK1; the activated transcription factors including e.g. NF-kappaB, c-Fos, c-Jun, c-Myc, CREB, AP-1, Elk-1, ATF2, IRF-3, IRF-7, or an isoform, homolog, fragment, variant or derivative of any of these proteins.

[0209] Adjuvant (preferably mammalian) (poly-)peptides or proteins or proteins may further be selected from the group consisting of heat shock proteins, such as HSP10, HSP60, HSP65, HSP70, HSP75 and HSP90, gp96, Fibrinogen, TypIII repeat extra domain A of fibronectin; or components of the complement system including Clq, MBL, Clr, Cls, C2b, Bb, D, MASP-1, MASP-2, C4b, C3b, C5a, C3a, C4a, C5b, C6, C7, C8, C9, CR1, CR2, CR3, CR4, ClqR, C1INH, C4bp, CP, DAF, H, I, P and CD59, or induced target genes including e.g. Beta-Defensin, cell surface proteins; or human adjuvant proteins including trif, flt-3 ligand, Gp96 or fibronectin, etc., or an isoform, homolog, fragment, variant or derivative of any of these proteins.

[0210] Adjuvant (preferably mammalian) (poly-)peptides or proteins or proteins may further be selected from the group consisting of cytokines which induce or enhance an innate immune response, including IL-1 alpha, IL1 beta, IL-2, IL-6, IL-7, IL-8, IL-9, IL-12, IL-13, IL-15, IL-16, IL-17, IL-18, IL-21, IL-23, TNFalpha, IFNalpha, IFNbeta, IFNgamma, GM-CSF, G-CSF, M- CSF; chemokines including IL-8, IP-10, MCP-1, MIP-lalpha, RANTES, Eotaxin, CCL21; cytokines which are released from macrophages, including IL-1, IL-6, IL-8, IL-12 and TNF-alpha; IL-1R1 and IL-1 alpha, or an isoform, homolog, fragment, variant or derivative of any of these proteins.

[0211] The term "antibody" (Ab) as used herein includes monoclonal antibodies, polyclonal antibodies, mono- and multispecific antibodies (e.g., bispecific antibodies), and antibody fragments, variants and derivatives so long as they exhibit the desired biological function, which is typically the capability of specifically binding to a target. The term "specifically binding" as used herein means that the antibody binds more readily to its intended target than to a different, non-specific target. In other words, the antibody "specifically binds" or exhibits "binding specificity" to its target if it preferentially binds or recognizes the target even in the presence of non-targets as measurable by a quantifiable assay (such as radioactive ligand binding Assays, ELISA, fluorescence based techniques (e.g. Fluorescence Polarization (FP), Fluorescence Resonance Energy Transfer (FRET)), or surface plasmon resonance). An antibody that "specifically binds" to its target may or may not exhibit cross-reactivity to (homologous) targets derived from different species.

[0212] The basic, naturally occurring antibody is a heterotetrameric glycoprotein composed of two identical light (L) chains and two identical heavy (H) chains. Some antibodies may contain additional polypeptide chains, such as the J chain in IgM and IgA antibodies. Each L chain is linked to an H chain by one covalent disulfide bond, while the two H chains are linked to each other by one or more disulfide bonds depending on the H chain isotype. Each H and L chain also comprises intrachain disulfide bridges. Each H chain comprises an N-terminal variable domain (VH), followed by three constant domains (CH) for each of the a and γ chains and four CH domains for μ and ε isotypes. Each L chain has at the N-terminus, a variable domain (VL) followed by a constant domain at its other end. The VLis aligned with the VH and the Q. is aligned with the first constant domain of the heavy chain (CH1). Particular amino acid residues are believed to form an interface between the light chain and heavy chain variable domains.

[0213] The L chain from any vertebrate species can be assigned to one of two clearly distinct types, called kappa and lambda, based on the amino acid sequences of their constant domains. Depending on the amino acid sequence of the constant domain of their heavy chains (CH), immunoglobulins can be assigned to different classes or isotypes. There are five classes of immunoglobulins: IgA, IgD, IgE, IgG and IgM, having heavy chains designated α, β, ε, γ and μ, respectively. The γ and μ classes are further divided into subclasses on the basis of relatively minor differences in the CH sequence and function, e.g., humans express the following subclasses: IgGl, IgG2, IgG3, IgG4, IgAl and IgA2.

[0214] The pairing of a H and VLtogether forms a single antigen-binding site. The term "variable" refers to the fact that certain segments of the variable domains differ extensively in sequence among antibodies. The V domain mediates antigen binding and defines the specificity of a particular antibody for its particular antigen. However, the variability is not evenly distributed across the entire span of the variable domains. Instead, the V regions consist of relatively invariant stretches called framework regions (FRs) of about 15-30 amino acid residues separated by shorter regions of extreme variability called "hypervariable regions" also called "complementarity determining regions" (CDRs) that are each approximately 9-12 amino acid residues in length. The variable domains of native heavy and light chains each comprise four FRs, largely adopting a β-sheet configuration, connected by three hypervariable regions, which form loops connecting, and in some cases forming part of, the β-sheet structure. The hypervariable regions in each chain are held together in close proximity by the FRs and, with the hypervariable regions from the other chain, contribute to the formation of the antigen binding site of antibodies. The constant domains are not involved directly in binding an antibody to an antigen, but exhibit various effector functions, such as participation of the antibody dependent cellular cytotoxicity (ADCC). The term "hypervariable region" (also known as "complementarity determining regions" or CDRs) when used herein refers to the amino acid residues of an antibody which are (usually three or four short regions of extreme sequence variability) within the V-region domain of an immunoglobulin which form the antigen-binding site and are the main determinants of antigen binding specificity. CDR residues may be identified based on cross-species sequence variability or crystallographic studies of antigen-antibody complexes.

[0215] The term "antibody" as used herein thus preferably refers to immunoglobulin molecules, or variants, fragments or derivatives thereof, which are capable of specifically binding to a target epitope via at least one complementarity determining region. The term includes mono-, and polyclonal antibodies, mono-, bi- and multispecific antibodies, antibodies of any isotype, including IgM, IgD, IgG, IgA and IgE antibodies, and antibodies obtained by any means, including naturally occurring antibodies, antibodies generated by immunization in a host organism, antibodies which were isolated and identified from naturally occurring antibodies or antibodies generated by immunization in a host organism and recombinantly produced by biomolecular methods known in the art, as well as chimeric antibodies, human antibodies, humanized antibodies, intrabodies, i.e. antibodies expressed in cells and optionally localized in specific cell compartments, as well as variants, fragments and derivatives of any of these antibodies.

[0216] The term "monoclonal antibody" (mab) as used herein refers to an antibody obtained from a population of substantially homogeneous antibodies, i.e., the individual antibodies comprising the population are identical except for possible naturally-occurring mutations that may be present in minor amounts. Monoclonal antibodies are highly specific, being directed against a single antigenic site. Furthermore, in contrast to "polyclonal" antibody preparations which include different antibodies directed against different epitopes, each monoclonal antibody is directed against a single epitope on the antigen. In addition to their specificity, the monoclonal antibodies are advantageous in that they may be synthesized uncontaminated by other antibodies. The adjective "monoclonal" is not to be construed as requiring production of the antibody by any particular method. For example, the monoclonal antibodies useful in the present invention may be prepared by the hybridoma methodology first described by Kohler et al., Nature 256: 495 (1975), or they may be made using recombinant DNA methods in bacterial or eukaryotic animal or plant cells (see, e.g., U.S. Pat. No. 4,816,567). The "monoclonal antibodies" may also be isolated from phage antibody libraries using the techniques described in Clackson et al., Nature 352: 624-628 (1991) and Marks et al., J. Mo / . Biol. 222: 581-597 (1991), for example.

[0217] Monoclonal antibodies include "chimeric" antibodies in which a portion of the heavy and / or light chain is identical with or homologous to corresponding sequences in antibodies derived from a particular species or belonging to a particular antibody class or subclass, while the remainder of the chain(s) is identical with or homologous to corresponding sequences in antibodies derived from another species or belonging to another antibody class or subclass. Chimeric antibodies include, e.g., "humanized" antibodies comprising variable domain antigen-binding sequences (partly or fully) derived from a non- human animal, e.g. a mouse or a non-human primate (e.g., Old World Monkey, Ape, etc.), and human constant region sequences, which are preferably capable of effectively mediating Fc effector functions, and / or exhibit reduced immunogenicity when introduced into the human body. "Humanized" antibodies may be prepared by creating a "chimeric" antibody (non-human Fab grafted onto human Fc) as an initial step and selective mutation of the (non-CD ) amino acids in the Fab portion of the molecule. Alternatively, "humanized" antibodies can be obtain directly by grafting appropriate "donor" CDR coding segments derived from a non-human animal onto a human antibody "acceptor" scaffold, and optionally mutating (non-CDR) amino acids for optimized binding.

[0218] An "antibody variant" or "antibody mutant" refers to an antibody comprising or consisting of an amino acid sequence wherein one or more of the amino acid residues have been modified as compared to a reference or "parent" antibody. Such antibody variants may thus exhibitin, increasing order of preference, at least about 5%, 10%, 20%, 30%, 40%, 50%, 60%, preferably at least about 70%, 80%, 85%, 86%, 87%, 88%, 89%, more preferably at least about 90%, 91%, 92%, 93%, 94%, most preferably at least about 95%, 96%, 97%, 98%, or 99% sequence identity to a reference or "parent" antibody, or to its light or heavy chain. Conceivable amino acid mutations include deletions, insertions or alterations of one or more amino acid residue(s). The mutations may be located in the constant region or in the antigen binding region (e.g., hypervariable or variable region). Conservative amino acid mutations, which change an amino acid to a different amino acid with similar biochemical properties (e.g. charge, hydrophobicity and size), may be preferred.

[0219] An "antibody fragment" comprises a portion of an intact antibody (i.e. an antibody comprising an antigen-binding site as well as a O. and at least the heavy chain domains, 04, CH2 and CH3), preferably the antigen binding and / or the variable region of the intact antibody. Examples of antibody fragments include Fab, Fab', F(ab')2 and Fv fragments; diabodies; linear antibodies, single-chain antibodies, and bi- or multispecific antibodies comprising such antibody fragments.

[0220] Papain digestion of antibodies produced two identical antigen-binding fragments, called "Fab" (fragment, antigen-binding) fragments, and a residual "Fc" (fragment, crystallisable) fragment. The Fab fragment consists of an entire L chain along with the variable region domain of the H chain (VH), and the first constant domain of one heavy chain (04). Each Fab fragment is monovalent with respect to antigen binding, i.e., it has a single antigen-binding site. Pepsin treatment of an antibody yields a single large F(ab')2fragment which roughly corresponds to two disulfide linked Fab fragments having different antigen-binding activity and is still capable of cross-linking antigen, and a pFc' fragment. The F(ab')2 fragment can be split into two Fab' fragments. Fab' fragments differ from Fab fragments by having a few additional residues at the carboxy terminus of the Q domain including one or more cysteines from the antibody hinge region. Fab'-SH is the designation herein for Fab' in which the cysteine residue(s) of the constant domains bear a free thiol group. F(ab')2 antibody fragments originally were produced as pairs of Fab' fragments which have hinge cysteines between them. Other antibody fragments and chemical fragments thereof are also known. The Fab / c or Fabc antibody fragment lacks one Fab region. Fd fragments correspond to the heavy chain portion of the Fab and contain a C-terminal constant (04) and H- terminal variable (VH) domain.

[0221] The Fc fragment comprises the carboxy-terminal portions of both H chains held together by disulphides. The effector functions of antibodies are determined by sequences in the Fc region, the region which is also recognized by Fc receptors (FcR) found on certain types of cells.

[0222] "Fv" is the minimum antibody fragment which contains a complete antigen-binding site. This fragment consists of a dimer of one heavy- and one light-chain variable region domain in tight, non-covalent association. From the folding of these two domains emanate six hypervariable loops (3 loops each from the H and L chain) that contribute the amino acid residues for antigen binding and confer antigen binding specificity to the antibody. However, even a single variable domain (or half of an Fv comprising only three CDRs specific for an antigen) has the ability to recognize and bind antigen, although at a lower affinity than the entire binding site.

[0223] "Single-chain Fv" also abbreviated as "sFv" or "scFv" are antibody fragments that comprise the VH and VL antibody domains connected into a single polypeptide chain. Preferably, the sFv polypeptide further comprises a polypeptide linker between the VH and VL domains which enables the sFv to form the desired structure for antigen binding.

[0224] The term "diabodies" (also referred to as divalent (or bivalent) single-chain variable fragments, "di-scFvs", "bi-scFvs") refers to antibody fragments prepared by linking two scFv fragments (see preceding paragraph), typically with short linkers (about 5-10) residues) between the VHand VLdomains such that inter-chain but not intra-chain pairing of the V domains is achieved. Another possibility is to construct a single peptide chain with two VHand two VLregions ("tandem scFv). The resulting bivalent fragments, have two antigen-binding sites. Likewise, trivalent scFv trimers (also referred to as "triabodies" or "tribodies") and tetravalent scFv tetramers ftetrabodies") can be produced. Di- or multivalent antibodies or antibody fragments may be monospecific, i.e. each antigen binding site may be directed against the same target. Such monospecific di- or multivalent antibodies or antibody fragments preferably exhibit high binding affinities. Alternatively, the antigen binding sites of di- or multivalent antibodies or antibody fragments may be directed against different targets, forming bi- or multispecific antibodies or antibody fragments.

[0225] "Bi- or multispecific antibodies or antibody fragments" comprise more than one specific antigen-binding region, each capable of specifically binding to a different target. "Bispecific antibodies" are typically heterodimers of two "crossover" scFv fragments in which the VHand VLdomains of the two antibodies are present on different polypeptide chains. Bi- or multispecific antibodies may act as adaptor molecules between an effector and a respective target, thereby recruiting effectors (e.g. toxins, drugs, and cytokines or effector cells such as CTL, NK cells, macrophages, and granulocytes) to an antigen of interest, typically expressed by a target cell, such as a cancer cell. Thereby, "bi- or multispecific antibodies" preferably bring the effector molecules or cells and the desired target into close proximity and / or mediate an interaction between effector and target. Bispecific tandem di-scFvs, known as bi-specific T-cell engagers (BiTE antibody constructs) are one example of bivalent and bispecific antibodies in the context of the present invention.

[0226] The structure and properties of antibodies is well-known in the art and described, inter alia, in Janeway's Immunobiology, 9thed. (rev.), Kenneth Murphy and Casey Weaver (eds), Taylor & Francis Ltd. 2008. The term "immunoglobulin" (Ig) is used interchangeably with "antibody" herein. Exemplary antibodies may be selected from the group consisting of AAB- 003; Abagovomab; Abciximab; Abituzumab; Abrilumab; Actoxumab; Adalimumab; Aducanumab; Afasevikumab; Aflibercept; Afutuzuab; Afutuzumab; Alacizumab_pegol; Alemtuzumab; Alirocumab; ALX-0061; Amatuximab; Anetumab_ravtansine; Anifrolumab; Anrukinzumab; Apolizumab; Apomab; Aquaporumab; Arcitumomab_99tc; Ascrinvacumab; Aselizuab; Atezolizumab; Atinumab; Atlizuab; Aurograb; Avelumab; Bapineuzumab; Basiliximab; Bavituximab; Begelomab; Benralizumab; Betalutin; Bevacituzuab; Bevacizumab_154-aspartic_acid; Bevacizumab_154- substitution; Bevacizumab_180-serine; Bevacizumab_180-substitution; Bevacizumab_beta; Bevacizumab; Bevacizumab- rhuMAb-VEGF; Bezlotoxumab; Bimagrumab; Bimekizumab; Bleselumab; Blinatumomab; Blinatumumab; Blontuvetmab; Blosozumab; Bococizumab; Brentuximab_vedotin; Briakinumab; Brodalumab; Brolucizumab; Brontictuzumab; BTT-1023; Burosumab; Canakinumab; Cantuzumab; Cantuzumabjriertansine; Cantuzumab_ravtansine; Caplacizumab; Carlumab; Cergutuzumab_amunaleukin; Certolizumab_pegol; Cetuximab; Citatuzumab_bogatox; Cixutumumab; Clazakizumab; Clivatuzumabjetraxetan; Codrituzumab; Coltuximab_ravtansine; Conatumumab_CV; Conatumumab; Concizumab; Crenezumab; Crotedumab; Dacetuzumab; Dacliximab; Daclizumab; Dalotuzumab; Dapirolizumab_pegol; Daratumumab; Dectrekumab; Demcizumab; Denintuzumab_mafodotin; Denosumab; Depatuxizumab; Depatuxizumab_mafodotin; Dinutuximab_beta; Dinutuximab; Diridavumab; Domagrozumab; Drozituab; Drozitumab; Duligotumab; Duligotuzumab; Dupilumab; Durvalumab; Dusigitumab; Ecromeximab; Eculizumab; Efalizumab; Efungumab; Eldelumab; Elgemtumab; Elotuzumab; Emactuzumab; Emibetuzumab; Emicizumab; Enavatuzumab; Enfortumab; Enfortumab_vedotin; Enoblituzumab; Enokizumab; Enoticumab; Ensituximab; Entolimod; Epratuzumab; Eptacog_beta; Erlizuab; Etaracizumab; Etrolizuab; Etrolizumab; Evinacumab; Evolocumab; Exbivirumab; Farletuzumab; Fasinumab; Fezakinumab; FG-3019; Fibatuzumab; Ficlatuzumab; Figitumumab; Firivumab; Flanvotumab; Fletikumab; Fontolizumab; Foralumab; Foravirumab; Fresolimumab; Fulranumab; Futuximab; Galcanezumab; Galiximab; Ganitumab; Gantenerumab; Gemtuzumab; Gemtuzumab_ozogamicin; Gevokizumab; Girentuximab; Glembatumumab; Goilixiab; Guselkumab; HuMab-001; HuMab- 005; HuMab-006; HuMab-019; HuMab-021; HuMab-025; HuMab-027; HuMab-032; HuMab-033; HuMab-035; HuMab-036; HuMab-041; HuMab-044; HuMab-049; HuMab-050; HuMab-054; HuMab-055; HuMab-059; HuMab-060; HuMab-067; HuMab-072; HuMab-084; HuMab-091; HuMab-093; HuMab-098; HuMab-100; HuMab-106; HuMab_10F8; HuMab-111; HuMab-123; HuMab-124; HuMab-125; HuMab-127; HuMab-129; HuMab-132; HuMab-143; HuMab-150; HuMab-152; HuMab-153; HuMab-159; HuMab-160; HuMab-162; HuMab-163; HuMab-166; HuMab-167; HuMab-169; HuMab-7D8; huMAb-anti-MSP10.1; huMAb-anti-MSP10.2; HUMAB-Clone_18; HUMAB-Clone_22; HuMab-L612; HuMab_LC5002-002; HuMab_LC5002-003; HuMab_LC5002-005; HuMab_LC5002-007; HuMab_LC5002-018; Ibalizumab; Ibritumomab_tiuxetan; Icrucumab; Idarucizumab; Igatuzuab; IGF-IR_HUMAB-1A; IGF-IR_HUMAB-23; IGF-IR_HUMAB-8; ImAbl; Imalumab; Imgatuzumab; Inclacumab; Indatuximab_ravtansine; Indusatumab_vedotin; Inebilizumab; Insulin_peglispro; Interferon_beta-lb; Intetumumab; Iodine_(124I)_Girentuximab; Iodine_(131I)_Derlotuxiab_biotin; Iodine_(131I)_Derlotuximab_biotin; Ipilimumab; Iratumumab; Isatuximab; Itolizumab; Ixekizumab; Labetuzumab_govitecan; Lambrolizumab; Lampalizumab; Lanadelumab; Landogrozumab; Laprituximab_emtansine; Lealesoab; Lebrikizumab; Lenercept_chainl; Lenzilumab; Lerdelimumab; Lexatumumab; Libivirumab; Lifastuzumab; Lifastuzumab_vedotin; Ligelizumab; Lilotomab; Lintuzumab; Lirilumab; Lodelcizumab; Lokivetmab; Lorvotuzumab_mertansine; Lpathomab; Lucatumumab; Lulizumab_pegol; Lumiliximab; Lumretuzumab; Lutetium_(177Lu)_lilotomab_satetraxetan; argetuximab; Marzeptacog_alfa; atuzumab; Mavrilimumab; DX-1303; Mepolizumab; Metelimumab; Milatuzumab; Mirvetuximab; Modotuximab; ogamulizumab; Monalizumab; Motavizumab; Moxetumomab_pasudotox; uromonab-CD3; Namilumab; Naptumomab_estafenatox; Narnatumab; Natalizumab; Navicixizumab; Navivumab; Ndimab-varB; Necitumumab; Neliximab; Nemolizumab; Nesvacumab; Neuradiab; Nimotuzumab; Nivolumab; Obiltoxaximab; Obinutuzumab; Ocaratuzumab; Ocrelizumab; Ofatumumab; Olaratumab; Olizuab; Oiokizumab; Omalizumab; Onartuzumab; Ontuxizumab; Opicinumab; Oportuzumab_monatox; Oreptacog_alfa; Orticumab; Otelixizumab; Otlertuzumab; Oxelumab; Ozanezumab; Ozoralizumab; Palivizumab; Pamrevlumab; Panitumumab; Pankoab; PankoMab; Panobacumab; Parsatuzumab; Pascolizumab; Pasotuxizumab; Pateclizumab; Patritumab; Pembrolizumab; Perakizumab; Pertuzuab; Pertuzumab; Pexelizumab_h5gl.l-scFv; Pexelizumab; PF- 05082566; PF-05082568; Pidilizumab; Pinatuzumab_vedotin; Placulumab; Plozalizumab; Pogalizumab; Polatuzumab_vedotin; Ponezumab; Pritoxaximab; Pritumumab; Quilizumab; Racotumomab; Radretumab; Raflvirumab; Ralpancizumab; Ramucirumab; Ranibiziuab; Ranibizumab; Refanezumab; REGN2810; rhuMab_HER2(9CI); rhuMab_HER2; rhuMAb-VEGF; Rilotumumab; Rinucumab; Risankizumab; Rituximab; Rivabazumab_pegol; Robatumumab; Roledumab; Romosozumab; Rontalizuab; Rontalizumab; Rovalpituzumab_tesirine; Rovelizumab; Ruplizumab; Sacituzumab_govitecan; Samalizumab; Sarilumab; Satumomab_pendetide; Secukinumab; Seribantumab; Setoxaximab; Sifalimumab; Siltuximab; Simtuzumab; Sirukumab; Sofituzumab_vedotin; Solanezumab; Solitomab; Sonepcizumab; Stamulumab; Suptavumab; Suvizumab; Tabalumab; Tacatuzuab; Tadocizumab; Talizumab; Tamtuvetmab; Tanezumab; Tarextumab; Tefibazumab; Tenatumomab; Teneliximab; Teplizumab; Teprotumumab; Tesidolumab; Tezepelumab; ThioMAb-chMA79b-HC(A118C); Thio ab-hulOA8.vl-HC(A118C); ThioMab-hulOA8.vl-HC(V205C); Thio ab-hulOA8.vl-LC(A118C); ThioMab-hulOA8.vl- LC(V205C); ThioMAb-huMA79b.vl7-HC(A118C); ThioMAb-huMA79b.vl8-HC(A118C); ThioMAb-huMA79b.v28-HC(A118C); ThioMAb-huMA79b.v28-LC(V205C); Ticiliuab; Tigatuzumab; Tildrakizumab; Tisotumab_vedotin; Tocilizumab; Tosatoxumab; Tositumomab; Tovetumab; Tralokinumab; Trastuzuab; Trastuzumab_emtansine; Trastuzumab; TRC-105; Tregalizumab; Tremelimumab; Trevogrumab; Tucotuzumab_celmoleukin; Ublituximab; Ulocuplumab; Urelumab; Urtoxazumab; Ustekinumab; Vadastuximab_talirine; Vandortuzumab_vedotin; Vantictumab; Vanucizumab; Varlilumab; Vatelizumab; Vedolizumab; Veltuzumab; Vesencumab; Visilizumab; Volociximab; Vorsetuzumab; Vorsetuzumab_mafodotin; Yttrium_(90Y)_clivatuzumab_tetraxetan; Yttrium_Y_90_epratuzumab_tetraxetan; Yttrium_Y_90_epratuzumab; Zalutumumab; Zanolimumab; Zatuximab; Andecaliximab; Aprutumab; Azintuxizumab; Brazikumab; Cabiralizumab; Camrelizumab; Cosfroviximab; Crizanlizumab; Dezamizumab; Duvortuxizumab; Elezanumab; Emapalumab; Eptinezumab; Erenumab; Fremanezumab; Frunevetmab; Gatipotuzumab; Gedivumab; Gemetuzumab; Gilvetmab; Ifabotuzumab; Lacnotuzumab; Larcaviximab; Lendalizumab; Lesofavumab; Letolizumab; Losatuxizumab; Lupartumab; Lutikizumab; Oleclumab; Porgaviximab; Prezalumab; Ranevetmab; Remtolumab; Rosmantuzumab; Rozanolixizumab; Sapelizumab; Selicrelumab; Suvratoxumab; Tavolixizumab; Telisotuzumab; Telisotuzumab_vedotin; Timigutuzumab; Timolumab; Tomuzotuximab; Trastuzumab_duocarmazine; Varisacumab; Vunakizumab; Xentuzumab; anti-rabies_S057; anti-rabies_SOJB; anti-rabies_SOJA; anti-rabies; anti-RSV_5ITB; anti-alpha-toxin_4U6V; anti- IsdB_5DlQ; anti-IsdB_5DlX; anti-IsdB_5DlZ; anti-HIV_bl2; anti-HIV_2G12; anti-HIV_4E10; anti-HIV_VRC01; anti- HIV_PG9; anti-HIV VRC07; anti-HIV_3BNC117; anti-HIV_10-1074; anti-HIV_PGT121; anti-HIV_PGDM1400; anti-HIV_N6; anti-HIV_10E8; anti-HIV_12A12; anti-HIV_12A21; anti-HIV_35022; anti-HIV_3BC176; anti-HIV_3BNC55; anti- HIV_3BNC60; anti-HIV_447-52D; anti-HIV_5H / Il-BMV-D5; anti-HIV_8ANC195; anti-HIV_cap256-176- 723043 / 600049 / 531926 / 504134; anti-HIV_CAP256-VRC26.01 / VRC26.02 / VRC26.03 / VRC26.04 / VRC26.05 / VRC26.06 / VRC26.07 / VRC26.08 / VRC26.09 / VRC26.10 / VRC26.11 / VRC26.12 / VRC26.I1 / VRC26.I2 / VRC26.UCA; anti-HIV_cap256-206- 252885 / 249183 / 220956 / 220629 / 200599 / 186347 / 186226 / 179686 / 173707 / 173339 / 172689 / 162744 / 146057 / 139519 / 1363 16 / 116098 / 115862 / 107018 / 098644 / 098135 / 096276 / 092794 / 086817 / 086446 / 086180 / 083708 / 079556 / 078657 / 075802 / 0 69097 / 067758 / 057019 / 055385 / 053187 / 053139 / 050350 / 046207 / 043389 / 042555 / 029720 / 028848 / 027652 / 024075 / 00874

[0227] 8 / 008530; anti-HIV_cap256-119-186229 / 183891 / 183631 / 182676 / 180772 / 180508 / 180260 / 180173 / 179839 / 179262 /

[0228] 178995 / 178455 / 177993 / 177727 / 176746 / 176241 / 175215 / 173928 / 173495 / 172882 / 172429 / 172223 / 171838 / 171587 / 1695

[0229] 96 / 169523 / 169462 / 169092 / 168680 / 166385 / 165943 / 165738 / 164913 / 164167 / 163558 / 162043 / 161718 / 161675 / 161053 / 1

[0230] 59499 / 159114 / 156751 / 155656 / 154420 / 153954 / 153864 / 153793 / 153462 / 153124 / 153025 / 152713 / 151794 / 150980 / 14889

[0231] 5 / 148848 / 148743 / 148595 / 148490 / 148470 / 148107 / 147933 / 147434 / 146106 / 145604 / 143998 / 143441 / 141307 / 140896 / 14

[0232] 0090 / 140037 / 139135 / 137881 / 137643 / 137170 / 136616 / 136206 / 135565 / 135025 / 133983 / 133917 / 132663 / 132113 / 131839

[0233] / 130626 / 130191 / 129798 / 128745 / 128593 / 128152 / 127693 / 126684 / 126056 / 125765 / 125106 / 124026 / 121783 / 121208 / 120

[0234] 945 / 118229 / 118025 / 117418 / 117250 / 117230 / 116999 / 116558 / 116484 / 114844 / 114141 / 111917 / 111862 / 110064 / 109192 /

[0235] 108793 / 108127 / 107758 / 107209 / 107184 / 106827 / 106511 / 106327 / 105486 / 105197 / 104946 / 103667 / 103385 / 103267 / 1030

[0236] 11 / 102072 / 101945 / 101319 / 100871 / 100838 / 100025 / 100000 / 098890 / 098715 / 098632 / 097199 / 096189 / 094581 / 094200 / 0

[0237] 94158 / 092814 / 092808 / 092573 / 090815 / 090368 / 089710 / 088555 / 087962 / 086903 / 086804 / 085910 / 085772 / 084603 / 08427

[0238] 6 / 082288 / 080383 / 079333 / 078618 / 077466 / 076284 / 074680 / 074081 / 071704 / 071266 / 069667 / 069591 / 068691 / 068488 / 06

[0239] 7536 / 065852 / 065457 / 064501 / 063568 / 063103 / 061027 / 058232 / 057341 / 056895 / 056402 / 056034 / 055042 / 054776 / 054539

[0240] / 054112 / 053339 / 052404 / 051123 / 051077 / 050442 / 049433 / 047532 / 047489 / 046020 / 044746 / 044740 / 043790 / 042880 / 042

[0241] 606 / 042444 / 040328 / 040164 / 039130 / 038138 / 037868 / 037102 / 036683 / 036495 / 035375 / 035165 / 035109 / 033789 / 033641 /

[0242] 032113 / 031739 / 030932 / 030740 / 030197 / 027047 / 026950 / 026279 / 025355 / 025301 / 025010 / 024631 / 024467 / 023805 / 0217

[0243] 36 / 021203 / 020569 / 019432 / 018827 / 018483 / 018118 / 017782 / 017669 / 016976 / 015432 / 015281 / 014957 / 014777 / 014313 / 0

[0244] 14219 / 013631 / 012924 / 011793 / 011413 / 011323 / 011233 / 009038 / 008756 / 008055 / 006949 / 006685 / 006015 / 005841 / 00582

[0245] 4 / 005494 / 004949 / 004422 / 003932 / 003577 / 002155 / 002017 / 001312 / 001017 / 000594; anti-HIV_cap256-059-241099 /

[0246] 207529 / 205541 / 188439 / 187234 / 187047 / 186068 / 182835 / 176659 / 172956 / 171272 / 168734 / 155838 / 149799 / 148168 / 1446

[0247] 85 / 140017 / 137547 / 131908 / 116006 / 115783 / 114609 / 113952 / 113878 / 113622 / 109427 / 109081 / 107590 / 107504 / 099614 / 0

[0248] 98972 / 097236 / 091487 / 089812 / 088468 / 088341 / 086533 / 086043 / 084191 / 082135 / 079417 / 076027 / 075082 / 072575 / 07192

[0249] 6 / 069638 / 069165 / 068956 / 068876 / 067733 / 067450 / 065694 / 065109 / 065060 / 064001 / 063270 / 061357 / 059834 / 059313 / 05

[0250] 7130 / 050520 / 049839 / 048503 / 045516 / 044188 / 044105 / 042100 / 040742 / 040554 / 039660 / 039298 / 037873 / 037633 / 036817

[0251] / 032787 / 032427 / 029390 / 027877 / 026640 / 026017 / 024100 / 023966 / 020534 / 019513 / 012963 / 010396 / 008136 / 006147 / 005

[0252] 081 / 005006 / 004451 / 003571 / 003449 / 002712 / 001573 / 001379 / 001029; anti-HIV_cap256-048-165087 / 158861 / 158280 /

[0253] 157928 / 157056 / 156422 / 152863 / 152770 / 150027 / 148246 / 147428 / 146603 / 145735 / 145116 / 144077 / 142876 / 140582 / 1393

[0254] 55 / 139151 / 137672 / 137506 / 137270 / 135447 / 131966 / 131008 / 129369 / 128476 / 128270 / 126220 / 125713 / 123934 / 122673 / 1

[0255] 22208 / 121552 / 120643 / 118458 / 118112 / 116469 / 113917 / 112368 / 112047 / 112029 / 110957 / 110526 / 109336 / 108152 / 10779

[0256] 9 / 107384 / 106530 / 106464 / 106411 / 106306 / 104496 / 103074 / 100832 / 100188 / 099645 / 098137 / 097878 / 097510 / 097313 / 09

[0257] 6626 / 096483 / 095691 / 095525 / 094783 / 094356 / 090756 / 089065 / 084986 / 083355 / 082462 / 082246 / 080752 / 078409 / 078273

[0258] / 078062 / 077798 / 073853 / 071661 / 071360 / 070955 / 070061 / 069669 / 069205 / 068882 / 067764 / 066845 / 065226 / 063717 / 063

[0259] 150 / 062431 / 060745 / 060420 / 060014 / 059747 / 058393 / 058159 / 057127 / 056251 / 055421 / 054989 / 054759 / 052573 / 051477 /

[0260] 051299 / 050815 / 049884 / 049170 / 048531 / 048259 / 047313 / 046596 / 044781 / 042599 / 041276 / 040200 / 039061 / 038515 / 0382

[0261] 55 / 038177 / 035513 / 034112 / 033983 / 032688 / 031092 / 030464 / 030289 / 030261 / 029362 / 027638 / 027613 / 026627 / 026239 / 0

[0262] 25518 / 024854 / 024537 / 021781 / 021758 / 020988 / 020663 / 020590 / 019765 / 019254 / 018073 / 016775 / 016069 / 015867 / 01567

[0263] 3 / 015156 / 014521 / 014475 / 013798 / 013271 / 013180 / 012148 / 011870 / 011530 / 010968 / 010224 / 009749 / 009623 / 008234 / 00

[0264] 8149 / 007301 / 007174 / 007079 / 007033 / 006128 / 005999 / 005394 / 004226 / 004097 / 003289 / 002601 / 002129 / 001875 / 001302

[0265] / 001203 / 000383; anti-HIV_cap256-038-261791 / 241540 / 235677 / 234314 / 234273 / 223164 / 220289 / 220020 / 216853 /

[0266] 213466 / 213212 / 213120 / 212592 / 211790 / 209916 / 207938 / 202245 / 197721 / 196679 / 196118 / 195382 / 180001 / 178021 / 1771

[0267] 04 / 171261 / 169090 / 168705 / 167685 / 158775 / 157318 / 153058 / 150027 / 146372 / 141868 / 141616 / 127989 / 118109 / 112226 / 1 05918 / 104487 / 102308 / 091115 / 090262 / 083260 / 080981 / 080873 / 074413 / 073153 / 064227 / 061640 / 059482 / 054000 / 05055

[0268] 4 / 044256 / 040944 / 040090 / 032874 / 025899 / 024581 / 013345 / 011559 / 009634 / 006730 / 004887 / 004840 / 002181 / 001902 / 00

[0269] 0976 / 000384; anti-HIV_048-250757 / 250716 / 250463 / 248153 / 247532 / 245846 / 244016 / 243682 / 243588 / 241775 / 237996 /

[0270] 237730 / 237253 / 234100 / 230882 / 229473 / 228238 / 228027 / 227795 / 227770 / 225298 / 225090 / 224187 / 223055 / 222711 / 2212

[0271] 09 / 220629 / 219430 / 216250 / 216133 / 214886 / 214709 / 214001 / 213230 / 212574 / 212207 / 209146 / 208206 / 208194 / 207744 / 2

[0272] 06501 / 204221 / 204015 / 201240 / 200455 / 200319 / 197896 / 193813 / 192098 / 191786 / 188746 / 185937 / 184849 / 183089 / 18150

[0273] 9 / 180990 / 177532 / 177426 / 177389 / 174266 / 172847 / 172845 / 172363 / 171609 / 170705 / 168381 / 166619 / 162036 / 160042 / 15

[0274] 9676 / 159500 / 159421 / 159333 / 158932 / 155811 / 155464 / 155392 / 155389 / 154449 / 153379 / 153171 / 152324 / 146102 / 145984

[0275] / 145371 / 144907 / 142298 / 142277 / 141934 / 141207 / 140796 / 139893 / 138820 / 135858 / 134968 / 134312 / 132253 / 130710 / 128

[0276] 564 / 126702 / 124521 / 122740 / 119536 / 116929 / 116577 / 116046 / 115875 / 115599 / 113988 / 112989 / 112435 / 111339 / 111055 /

[0277] 111027 / 109721 / 109666 / 109196 / 109051 / 108570 / 108033 / 107279 / 106271 / 106054 / 104848 / 104638 / 104567 / 102804 / 1016

[0278] 76 / 097603 / 097107 / 096871 / 096668 / 095236 / 094155 / 093219 / 092976 / 090866 / 090650 / 089009 / 088654 / 086513 / 086024 / 0

[0279] 85857 / 084277 / 084245 / 082487 / 081787 / 081062 / 079639 / 079126 / 073118 / 070264 / 069426 / 068564 / 068345 / 067337 / 06718

[0280] 0 / 063017 / 061885 / 061671 / 060700 / 060592 / 060300 / 059141 / 057777 / 056928 / 056131 / 055864 / 055094 / 054343 / 054193 / 05

[0281] 2521 / 049037 / 048720 / 048542 / 047777 / 046841 / 046202 / 046059 / 043568 / 042713 / 042440 / 040511 / 039195 / 036935 / 034478

[0282] / 031641 / 029760 / 027970 / 027337 / 027217 / 026760 / 024800 / 024313 / 021748 / 020991 / 020340 / 019993 / 019947 / 017871 / 015

[0283] 931 / 015920 / 013898 / 013429 / 012358 / 011158 / 010720 / 009445 / 006126 / 005652 / 005532 / 005189 / 005088 / 004023 / 001580; anti-HIV_119-099719 / 099536 / 098907 / 098555 / 097828 / 096480 / 095664 / 095212 / 094773 / 094508 / 093795 / 093732 /

[0284] 092903 / 092284 / 091586 / 091023 / 090334 / 088694 / 088499 / 088298 / 087488 / 087423 / 087371 / 087279 / 087146 / 087048 / 0858

[0285] 02 / 085784 / 085370 / 085276 / 084885 / 084874 / 084691 / 083793 / 083163 / 082331 / 082070 / 081512 / 080816 / 079302 / 079292 / 0

[0286] 79289 / 078935 / 078702 / 078593 / 077708 / 076904 / 075862 / 075465 / 074822 / 074629 / 074500 / 073911 / 072765 / 072313 / 07228

[0287] 0 / 071693 / 071353 / 069711 / 069061 / 068202 / 068063 / 067980 / 067866 / 067756 / 066859 / 065821 / 065191 / 064667 / 063791 / 06

[0288] 2989 / 062286 / 061416 / 061344 / 060240 / 060184 / 058035 / 057858 / 057473 / 057090 / 055754 / 054899 / 054501 / 051867 / 051814

[0289] / 051567 / 051483 / 050913 / 050187 / 049069 / 048517 / 048470 / 048303 / 048021 / 047928 / 047384 / 047145 / 046752 / 046660 / 046

[0290] 202 / 045790 / 044670 / 044140 / 042776 / 042581 / 040905 / 040322 / 039892 / 039764 / 039188 / 039058 / 038837 / 038396 / 036918 /

[0291] 036592 / 036310 / 035618 / 035569 / 035466 / 035157 / 035121 / 035046 / 034754 / 034318 / 033780 / 033632 / 033183 / 030696 / 0300

[0292] 59 / 029589 / 029448 / 029220 / 028317 / 028165 / 027147 / 026743 / 026508 / 025683 / 025614 / 025548 / 025526 / 023552 / 023092 / 0

[0293] 22793 / 022395 / 022334 / 021866 / 021278 / 021183 / 019376 / 019238 / 018500 / 018318 / 018218 / 017876 / 017740 / 017128 / 01704

[0294] 4 / 016644 / 015878 / 015538 / 015455 / 014425 / 013582 / 013364 / 012886 / 012249 / 012161 / 012110 / 012100 / 011651 / 011479 / 01

[0295] 1232 / 011175 / 008396 / 007148 / 007029 / 004707 / 003910 / 002450 / 001552; anti-HIV_CH01 / CH02 / CH03 / CH04 / CH103 /

[0296] M66.6 / NIH45-46 / PG16 / PGT122 / PGT123 / PGT125 / PGT126 / PGT127 / PGT128 / PGT130 / PGT131 / PGT135 / PGT136 / PGT137 /

[0297] PGT141 / PGT142 / PGT143 / PGT144 / PGT145 / PGT151 / PGT152 / VRC-CH30 / VRC-CH31 / VRC-CH32 / VRC-CH33 / VRC-

[0298] CH34 / VRC-PG04 / VRC-PG04b / VRC-PG20 / VRC02 / VRC03 / VRC23 / 5CC / 5AWN / 3QEG / lN0X / 3QEH / 2BlH / 3TNM / 3UJJ / 3UJI /

[0299] 2QSC / 3MLZ / 3MLX / 3MLW / 3MLV / 3MLU / 3 LT / 3^

[0300] VRC18.02 / 44-VRC13.02 / 45; anti-HIV_059-188169 / 183739 / 182376 / 182199 / 169202 / 155645 / 151619 / 146503 / 136098 / 105516 / 095709 / 069468 / 060026 / 053668 / 052864 / 050968 / 046422 / 045120 / 039932 / 038595 / 035082 / 029204 / 025235 / 0151 92 / 007060 / 006953 / 005953 / 003725 / 002618 / 001522 / 000731 / 000634; anti-HIV_206-314431; anti-HIV_206-247594; anti- HIV_206-116890; anti-HIV_206-072383; anti-HIV_206-037527; anti-HIV_206-009095; anti-HIV_176-503620; anti- HIV_176-478726; anti-HIV_176-245056; anti-HIV_176-164413; anti-HIV_176-094308; anti-HIV_176-065321; anti- HIV_038-221120; anti-HIV_038-197677; anti-HIV_038-196765; anti-HIV_038-186200; anti-HIV_038-126170; anti- HIV_038-108545; anti-HIV_038-107263; anti-HIV_038-104530; anti-HIV_038-099169; anti-HIV_038-075067; anti- HIV_038-072368; anti-HIV_038-068503; anti-HIV_038-068016; anti-HIV_038-063958; anti-HIV_038-033733; anti- HIV_038-030557; anti-HIV_038-024298; anti-HIV_038-011154;; anti-HIV_5CIN; anti-HIV_5CIL; anti-HIV_5CIP; anti- HIV_4J P; anti-HIV_3TNN; anti-HIV_3BQU; anti-HIVJgG; anti-HIV_4P9M; anti-HIV_4P9H; anti-HIV_Ig; anti-HIV; anti- influenza; anti-influenza_Apo; anti-influenza-A; and anti-OX40;or a homolog, fragment, variant or derivative of any of these antibodies.

[0301] Artificial nucleic acid molecules of the invention encoding preferred antibodies may preferably comprise a coding region comprising or consisting of a nucleic acid sequence according to any one of the SEQ ID NO: l to 61734 or respectively Table 3, Table 4, Table 5, Table 6 or Table 9 as described in international patent application PCT / EP2017 / 060226, in particular a nucleic acid sequence being identical or having a sequence identity of at least 50%, 60%, 70%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%, preferably at least 80%, to these sequences or a fragment or variant of any of these RNA sequences.In this context, the disclosure of PCT / EP2017 / 060226 is also incorporated herein by reference. The person skilled in the art knows that also other (redundant) mRNA sequences can encode the proteins as shown in the above reference, therefore the mRNA sequences are not limited thereto.

[0302] Artificial nucleic acid molecules of the invention encoding preferred therapeutic proteins may preferably comprise a coding region comprising or consisting of a nucleic acid sequence according to any one of the SEQ ID NO as shown in SEQ ID NO: l to SEQ ID NO:345916 or respectively Table I as described in U.S. Application No. 15 / 585,561, in particular a nucleic acid sequence being identical or having a sequence identity of at least 50%, 60%, 70%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%, preferably at least 80%, to these sequences or a fragment or variant of any of these RNA sequences. In this context, the disclosure of U.S. Application No. 15 / 585,561 is also incorporated herein by reference. The person skilled in the art knows that also other (redundant) mRNA sequences can encode the proteins as shown in the above reference, therefore the mRNA sequences are not limited thereto.

[0303] Further artificial nucleic acid molecules of the invention encoding preferred therapeutic proteins may preferably comprise a coding region comprising or consisting of a nucleic acid sequence according to any one of the SEQ ID NO as shown in SEQ ID NO: l to SEQ ID NO:345916 or respectively Table I as described in international patent application PCT / EP2017 / 060692, in particular a nucleic acid sequence being identical or having a sequence identity of at least 50%, 60%, 70%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%, preferably at least 80%, to these sequences or a fragment or variant of any of these RNA sequences. In this context, the disclosure of international patent application PCT / EP2017 / 060692 is also incorporated herein by reference. The person skilled in the art knows that also other (redundant) mRNA sequences can encode the proteins as shown in the above reference, therefore the mRNA sequences are not limited thereto.

[0304] The term "peptide hormone" refers to a class of peptides or proteins that have endocrine functions in living animals. Typically, peptide hormones exert their functions by binding to receptors on the surface of target cells and transmitting signals via intracellular second messengers. Exemplary peptide hormones include Adiponectin i.e. Acrp30; Adrenocorticotropic hormone (or corticotropin) i.e. ACTH; Amylin (or Islet Amyloid Polypeptide) i.e. IAPP; Angiotensinogen and angiotensin i.e. AGT; Anti-Mullerian hormone (or Mullerian inhibiting factor or hormone) i.e. AMH; Antidiuretic hormone (or vasopressin, arginine vasopressin) i.e. ADH; Atrial-natriuretic peptide (or atriopeptin) i.e. ANP; Brain natriuretic peptide i.e. BNP; Calcitonin i.e. CT; Cholecystokinin i.e. CCK; Corticotropin-releasing hormone i.e. CRH; Cortistatin i.e. CORT; Endothelin i.e. ; Enkephalin i.e. ; Erythropoietin i.e. EPO; Follicle-stimulating hormone i.e. FSH; Galanin i.e. GAL; Gastric inhibitory polypeptide i.e. GIP; Gastrin i.e. GAS; Ghrelin i.e. ; Glucagon i.e. GCG; Glucagon-like peptide-1 i.e. GLP1; Gonadotropin-releasing hormone i.e. Gn H; Growth hormone i.e. GH or hGH; Growth hormone-releasing hormone i.e. GHRH; Guanylin i.e. GN; Hepcidin i.e. HAMP; Human chorionic gonadotropin i.e. hCG; Human placental lactogen i.e. HPL; Inhibin i.e. ; Insulin i.e. INS; Insulin-like growth factor (or somatomedin) i.e. IGF; Leptin i.e. LEP; Lipotropin i.e. LPH; Luteinizing hormone i.e. LH; Melanocyte stimulating hormone i.e. MSH or a-MSH; Motilin i.e. MLN; Orexin i.e. ; Osteocalcin i.e. OCN; Oxytocin i.e. OXT; Pancreatic polypeptide i.e. Parathyroid hormone i.e. PTH; Pituitary adenylate cyclase-activating peptide i.e. PACAP; Prolactin i.e. PRL; Prolactin releasing hormone i.e. PRH; Relaxin i.e. RLN; Renin i.e. ; Secretin i.e. SCT; Somatostatin i.e. SRIF; Thrombopoietin i.e. TPO; Thyroid-stimulating hormone (or thyrotropin) i.e. TSH; Thyrotropin- releasing hormone i.e. TRH; Uroguanylin i.e. UGN; or Vasoactive intestinal peptide i.e. VIP, or an isoform, homolog, fragment, variant or derivative of any of these proteins.

[0305] The term "gene editing agent" refers to (poly-)peptides or proteins that are capable of modifying (i.e. alter, induce, increase, reduce, suppress, abolish or prevent) expression of a gene. Gene expression can be modified on several levels. Gene editing agents may typically act by (a) introducing or removing epigenetic modifications, (b) altering the sequence of genes, e.g. by introducing, deleting or changing nucleic acid residues in the nucleic acid sequence of a gene of interest (c) modifying the biological function of regulatory elements operably linked to the gene of interest (d) modifying mRNA transcription, processing, splicing, maturation or export into the cytoplasm, (e) modifying mRNA translation, (0 modifying post-translational modifications, (g) modifying protein translocation or export. In a narrower sense, the term "gene editing agent" may refer to (poly-)peptides or proteins targeting the genome of a cell to modify gene expression, preferably by exerting functions (a)-(d), more preferably (a)-(c). The term "gene editing agent" as used herein thus preferably encompasses gene editing agents that cleave or alter the targeted DNA to induce mutation (e.g., via homologous directed repair or non-homologous end-joining), but also includes gene editing agents that can reduce expression in the absence of target cleavage (e.g., gene editing agents that are fused or conjugated to expression modulators such as transcriptional repressors or epigenetic modifiers that can reduce gene expression). Particular gene editing agents include: transcriptional activators, transcriptional repressors, recombinases, nucleases, DNA-binding proteins, or combinations thereof.

[0306] The present invention also relates to artificial nucleic acids, in particular RNAs, encoding CRISPR-associated proteins, and (pharmaceutical) compositions and kit-of-parts comprising the same. Said artificial nucleic acids, in particular RNAs, (pharmaceutical) compositions and kits are inter alia envisaged for use in medicine, for instance in gene therapy, and in particular in the treatment and / or prophylaxis of diseases amenable to treatment with CRISPR-associated proteins, e.g. by gene editing, knock-in, knock-out or modulating the expression of target genes of interest.

[0307] The term "CRISPR-associated protein" refers to RNA-guided endonucleases that are part of a CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) system (and their homologs, variants, fragments or derivatives), which is used by prokaryotes to confer adaptive immunity against foreign DNA elements. CRISPR-associated proteins include, without limitation, Cas9, Cpfl (Casl2), C2cl, C2c3, C2c2, Casl3, CasX and CasY. As used herein, the term "CRISPR-associated protein" includes wild-type proteins as well as homologs, variants, fragments and derivatives thereof. Therefore, when referring to artificial nucleic acid molecules encoding Cas9, Cpfl (Casl2), C2cl, C2c3, and C2c2, Casl3, CasX and CasY, said artificial nucleic acid molecules may encode the respective wild-type proteins, or homologs, variants, fragments and derivatives thereof. Preferably, the at least one 5'UTR element and the at least one 3'UTR element act synergistically to increase the expression of the at least one coding sequence operably linked to said UTRs. It is envisaged herein to utilize the recited 5'-UTRs and 3'-UTRs in any useful combination. Further particulary preferred embodiments of the invention comprise the combination of the CDS of choice, i.e. a CDS selected from the group consisting of Cas9, Cpfl, CasX, CasY, and Casl3 with an UTR- combination selected from the group of HSD17B4 / Gnas.l; Slc7a3.1 / Gnas.l; ATP5A1 / CASP.l; Ndufa4.1 / PS B3.1; HSD17B4 / PSMB3.1; RPL32var / albumin7; 32L4 / albumin7; HSD17B4 / CASP1.1; Slc7a3.1 / CASP1.1; Slc7a3.1 / PSMB3.1; Nosip.l / PSMB3.1; Ndufa4.1 / RPS9.1; HSD17B4 / RPS9.1; ATP5A1 / Gnas.l; Ndufa4.1 / COX6B1.1; Ndufa4.1 / Gnas.l; Ndufa4.1 / Ndufal.l; Nosip.l / Ndufal.l; RpBl.l / Gnas.l; TUBB4B.1 / RPS9.1; and Ubqln2.1 / RPS9.1.

[0308] The term "immune checkpoint inhibitor" refers to any (poly-)peptide or protein capable of inhibiting (i.e. interfering with, blocking, neutralizing, reducing, suppressing, abolishing, preventing) the biological activity of an immune checkpoint protein. Immune checkpoint proteins typically regulate T-cell activation or function and are well known in the art. Immune checkpoint proteins include, without limitation, CTLA-4, PD-1, VISTA, B7-H2, B7-H3, PD-L1 (B7-H1, CD274), B7-H4, B7- H6, 2B4, ICOS, HVEM, PD-L2 (B7-DC, CD273), CD2, CD27, CD28, CD30, CD40, CD70, CD80, CD86, CD137, CD160, CD226, CD276, CD160, gp49B, PIR-B, KIR family receptors, TIM-1, TIM-3, TIM-4, LAG-3, BTLA, SIRPalpha (CD47), CD48, 2B4 (CD244), B7.1, B7.2, ILT-2, ILT-4, TIGIT, A2aR, DR3, IDOL, ID02, LAIR-2, LIGHT, MARCO (macrophage receptor with collagenous structure), PS (phosphatidylserine), OX-40, SLAM, TIGHT, VISTA, and / or VTCN1. Exemplary agents useful for inhibiting immune checkpoint proteins include antibodies (and antibody fragments, variants or derivatives), peptides, natural ligands (and ligand fragments, variants or derivatives), fusion proteins, that can either directly bind to (and thereby inactivate or inhibit) or indirectly inactivate or inhibit immune checkpoint proteins, e.g. by binding to, inactivating and / or inhibiting their receptors or downstream signalling molecules to block the interaction between one or more immune checkpoint proteins and their natural receptor(s) and / or to prevent inhibitory signalling mediated by binding of said immune checkpoint proteins and their natural receptor(s). Exemplary immune checkpoint inhibitors include A2AR; B7-H3 i.e. cD276; B7-H4 i.e. VTCNl; BTLA; CTLA-4; IDO i.e. Indoleamine 2,3-dioxygenase; KIR i.e. Killer-cell Immunoglobulin-like Receptor; LAG3 i.e. Lymphocyte Activation Gene-3; PD-1 i.e. Programmed Death 1 (PD-1) receptor; PD-L1, TIM-3 i.e. T-cell Immunoglobulin domain and Mucin domain 3; VISTA (protein) i.e. V-domain Ig suppressor of T cell activation; GITR, i.e. Glucocorticoid-Induced TNFR family Related gene; stimulatory checkpoint molecules i.e. CD27, CD40, CD122, OX40, GITR and CD137 or stimulatory checkpoint molecules belonging to the B7-CD28 superfamily, i.e. CD28 and ICOS, or an isoform, homolog, fragment, variant or derivative of any of these proteins.

[0309] The term "T cell receptor" or "TCR" refers to a T-cell specific protein receptor that is composed of a heterodimer of variable, disulphide-linked alpha (a) and beta ( ) chains, or of gamma and delta (γ / δ) chains, optionally forming a complex with domains for additional (co-)stimulatory signalling, such as the invariant CD3-zeta (ζ) chains and / or FcR, CD27, CD28, 4- 1BB (CD137), DAP10, and / or OX40. The term "T cell receptor" includes (engineered) variants, fragments and derivatives of such naturally occurring TCRs, including chimeric antigen receptors (CARs). The term "chimeric antigen receptor (CAR)" generally refers to engineered fusion proteins comprising binding domains fused to an intracellular signalling domain capable of activating T cells. Typically, CARs are chimeric polypeptide constructs comprising at least an extracellular antigen binding domain, a transmembrane domain and a cytoplasmic signalling domain (also referred to herein as "an intracellular signalling domain") comprising a functional signalling domain derived from a (co-)stimulatory molecule, such as the CD3- zeta chain, FcR, CD27, CD28, 4-1BB (CD137), DAP10, and / or OX40. The extracellular antigen-binding domain may typically be derived from a monoclonal antibody or a fragment, variant or derivative thereof. In particular aspects, CARs comprise fusions of single-chain variable fragments (scFv) derived from monoclonal antibodies, fused to CD3-zeta transmembrane and intracellular endodomain.

[0310] Artificial nucleic acid molecules of the invention encoding preferred sequences for the treatment of tumor or cancer diseases may preferably comprise a coding region comprising or consisting of a nucleic acid sequence according to any one of the SEQ ID NO:l to 10071, preferably SEQ ID NO:l, 3, 5, 6, 389, or 399, or respectively Tables 1 to 12 or Tables 14-17 as described in international patent application WO2016170176A1, in particular a nucleic acid sequence being identical or having a sequence identity of at least 50%, 60%, 70%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%, preferably at least 80%, to these sequences or a fragment or variant of any of these RNA sequences. In this context, the disclosure of WO2016170176A1 is also incorporated herein by reference. The person skilled in the art knows that also other (redundant) mRNA sequences can encode the proteins as shown in the above reference, therefore the mRNA sequences are not limited thereto.

[0311] Further artificial nucleic acid molecules of the invention encoding preferred sequences for the treatment of tumor or cancer diseases may preferably comprise a coding region comprising or consisting of a nucleic acid sequence according to any one of the SEQ ID NO SEQ ID NO as shown in international patent applications WO2009046974, WO2015024666, WO2009046739, WO2015024664, WO2003051401, WO2012089338, WO2013120627, WO2014127917, WO2016170176, or WO2015135558, in particular a nucleic acid sequence being identical or having a sequence identity of at least 50%, 60%, 70%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%, preferably at least 80%, to these sequences or a fragment or variant of any of these RNA sequences. In this context, the disclosure of WO2009046974, WO2015024666, WO2009046739, WO2015024664, WO2003051401, WO2012089338, WO2013120627, WO2014127917, WO2016170176, or WO2015135558 is also incorporated herein by reference. The person skilled in the art knows that also other (redundant) mRNA sequences can encode the proteins as shown in the above reference, therefore the mRNA sequences are not limited thereto.

[0312] The term "enzyme" is well-known in the art and refers to (poly-)peptide and protein catalysts of chemical reactions. Enzymes include whole intact enzyme or fragments, variants or derivatives thereof. Exemplary enzymes include oxidoreductases, transferases, hydrolases, lyases, isomerases, and ligases.

[0313] Fragments, variants and derivatives of the aforementioned therapeutic proteins are also envisaged as (poly-)peptides or proteins of interest, provided that they are preferably functional and thus capable of mediating the desired biological effect or function.

[0314] Antigenic (poly-)peptides or proteins

[0315] The at least one coding region of the artificial nucleic acid molecule of the invention may encode at least one "antigenic (poly-)peptide or protein". The term "antigenic (poly-)peptide or protein" or, shortly, "antigen" generally refers to any (poly-)peptide or protein capable, under appropriate conditions, of interacting with / being recognized by components of the immune system (such as antibodies or immune cells via their antigen receptors, e.g. B cell receptors (BCRs) or T cell receptors (TCRs)), and preferably capable of eliciting an (adaptive) immune response. The term "components of the immune system" preferably refers to immune cells, immune cell receptors and antibodies of the adaptive immune system. The "antigenic peptide or protein" preferably interacts with / is recognized by the components of the immune system via its "epitope(s)" or "antigenic determinant(s)". The term "epitope" or "antigenic determinant" refers to a part or fragment of an antigenic peptide or protein that recognized by the immune system. Said fragment may typically comprise from about 5 to about 20 or even more amino acids. Epitopes may be "conformational" (or "discontinuous"), i.e. composed of discontinuous sequences of the amino acids of the antigenic peptide or protein that they are derived from, but brought together in the three-dimensional structure of e.g. a MHC-complex, or "linear", i.e. consist of a continuous sequence of amino acids of the antigenic peptides or proteins that they are derived from. The term "epitope" generally encompasses "T cell epitopes" (recognized by T cells via their T cell receptor) and "B cell epitopes" (recognized by B cells via their B cell receptor). "B cell epitopes" are typically located on the outer surface of (native) protein or peptide antigens as defined herein, and may preferably comprise or consist of between 5 to 15 amino acids, more preferably between 5 to 12 amino acids, even more preferably between 6 to 9 amino acids. "T cell epitopes" are typically recognized by T cells in a MHC-I or MHC-II bound form, i.e. as a complex formed by an antigenic protein or peptide fragment comprising the epitope, and a MHC-I or MHC-II surface molecule. "T cell epitopes" may typically have a length of about 6 to about 20 or even more amino acids, T cell epitopes presented by MHC class I molecules may preferably have a length of about 8 to about 10 amino acids, e.g. 8, 9, or 10, (or even 11, or 12 amino acids). T cell epitopes presented by MHC class II molecules may preferably have a length of about 13 or more amino acids, e.g. 13, 14, 15, 16, 17, 18, 19, 20 or even more amino acids. In the context of the present invention, the term "epitope" may in particular refer to T cell epitopes.

[0316] Thus, the term "antigenic (poly-)peptide or protein" refers to a (poly-)peptide comprising, consisting of or being capable of providing at least one (functional) epitope. Artificial nucleic acid (RNA) molecules of the invention may encode full- length antigenic (poly-)peptides or proteins, or preferably fragments thereof. Said fragments may comprise or consist of or be capable of providing (functional) epitopes of said antigenic (poly-)peptides or proteins. A "functional" epitope refers to an epitope capable of inducing a desired adaptive immune response in a subject.

[0317] Artificial nucleic acid (RNA) molecules encoding, in their at least one coding region, at least one antigenic (poly-)peptide or protein may enter the target cells (e.g. professional antigen-presenting cells (APCs), where the at least one antigenic (poly-)peptide or protein is expressed, processed and presented to immune cells (e.g. T cells) on an MHC molecule, preferably resulting in an antigen-specific immune response (e.g. cell-mediated immunity or formation of antibodies). Alternatively, artificial nucleic acid (RNA) molecules encoding, in their at least one coding region, at least one antigenic (poly-)peptide or protein may enter the target cells (e.g. muscle cells, dermal cells) where the at least one antigenic (polypeptide or protein is expressed and for instance secreted by the target cell to the extracellular environment, where it encounters cells of the immune system (e.g. B cells, macrophages) and preferably induces an antigen-specific immune response (e.g. formation of antibodies).

[0318] When referring to an artificial nucleic acid (RNA) molecule encoding "at least one antigenic peptide or protein" herein, it is envisaged that said artificial nucleic acid (RNA) molecule may encode one or more full-length antigenic (poly-)peptide(s) or protein(s), or one or more fragment(s), in particular a (functional) epitope(s), of said antigenic (poly-)peptide or protein. Said full-length antigenic (poly-)peptide(s) or protein(s), or its fragment(s), preferably comprises, consists of or is capable of providing at least one (functional) epitope, i.e. said antigenic (poly-)peptide(s) or protein(s) or its fragment(s) preferably either comprise(s) or consist(s) of a native epitope (preferably recognized by B cells) or is capable of being processed and presented by an MHC-I or MHC-II molecule to provide a MHC-bound epitope (preferably recognized by T cells). The choice of particular antigenic (poly-)peptides or proteins generally depends on the disease to be treated or prevented. In general, the artificial nucleic acid (RNA) molecule, may encode any antigenic (poly-)peptide or protein associated with a disease amenable to treatment by inducing an immune response against said antigen (e.g. cancer, infections).

[0319] Preferably, artificial nucleic acid molecules according to the invention may comprise at least one coding region encoding a tumor antigen, a pathogenic antigen, an autoantigen, an alloantigen, or an allergenic antigen.

[0320] The term "tumor antigen" refers to antigenic (poly-)peptides or proteins derived from or associated with a (preferably malignant) tumor or a cancer disease. As used herein, the terms "cancer" and "tumor" are used interchangeably to refer to a neoplasm characterized by the uncontrolled and usually rapid proliferation of cells that tend to invade surrounding tissue and to metastasize to distant body sites. The term encompasses benign and malignant neoplasms. Malignancy in cancers is typically characterized by anaplasia, invasiveness, and metastasis; whereas benign malignancies typically have none of those properties. The terms "cancer" and "tumor" in particular refer to neoplasms characterized by tumor growth, but also to cancers of blood and lymphatic system. A "tumor antigen" is typically derived from a tumor / cancer cell, preferably a mammalian tumor / cancer cell, and may be located in or on the surface of a tumor cell derived from a mammalian, preferably from a human, tumor, such as a systemic or a solid tumor. "Tumor antigens" generally include tumor-specific antigens (TSAs) and tumor-associated-antigens (TAAs). TSAs typically result from a tumor specific mutation and are specifically expressed by tumor cells. TAAs, which are more common, are usually presented by both tumor and "normal" (healthy, non-tumor) cells.

[0321] The protein or polypeptide may comprise or consist of a tumour antigen, a fragment, variant or derivative of a tumour antigen. Such nucleic acid molecules are particularly useful for therapeutic purposes, particularly genetic vaccination. Preferably, the tumour antigen may be selected from the group comprising a melanocyte-specific antigen, a cancer-testis antigen or a tumour-specific antigen, preferably a CT-X antigen, a non-X CT-antigen, a binding partner for a T-X antigen or a binding partner for a non-X CT-antigen or a tumour-specific antigen, more preferably a CT-X antigen, a binding partner for a non-X CT-antigen or a tumour-specific antigen or a fragment, variant or derivative of said tumour antigen; and wherein each of the nucleic acid sequences encodes a different peptide or protein; and wherein at least one of the nucleic acid sequences encodes for 5T4, 707-AP, 9D7, AFP, AlbZIP HPG1, alpha-5-beta- 1 -integrin, alpha-5-beta-6-integrin, alpha- actinin-4 / m, alpha-methylacyl-coenzyme A racemase, A T-4, ARTCl / m, B7H4, BAGE-1, BCL-2, bcr / abl, beta-catenin / m, BING-4, BRCAI / m, BRCA2 / m, CA 1 5-3 / CA 27-29, CA 19-9, CA72-4, CA125, calreticulin, CAMEL, CASP-8 / m, cathepsin B, cathepsin L, CD19, CD20, CD22, CD25, CDE30, CD33, CD4, CD52, CD55, CD56, CD80, CDC27 / m, CDK4 / m, CDKN2A / m, CEA, CLCA2, CML28, CML66, COA-l / m, coactosin-like protein, collage XXIII, COX-2, CT-9 / BRD6, Cten, cyclin Bl, cyclin Dl, cyp-B, CYPB1, DAM-10, DAM-6, DEK-CAN, EFTUD2 / m, EGFR, ELF2 / m, EMMPRIN, EpCam, EphA2, EphA3, ErbB3, ETV6- AML1, EZH2, FGF-5, FN, Frau-1, G250, GAGE-1, GAGE-2, GAGE-3, GAGE-4, GAGE-5, GAGE-6, GAGE7b, GAGE-8, GDEP, GnT-V, gplOO, GPC3, GPNMB / m, HAGE, HAST-2, hepsin, Her2 / neu, HERV-K-MEL, HLA-A*0201 - Rl 71, HLA-A1 1 / m, HLA- A2 / m, HNE, homeobox NKX3.1, HOM-TES-14 / SCP-1, HOM-TES- 85, HPV-E6, HPV-E7, HSP70-2M, HST-2, hTERT, iCE, IGF- 1 R, IL-13Ra2, IL-2R, IL-5, immature laminin receptor, kallikrein-2, kallikrein-4, i67, KIAA0205, KIAA0205 / m, KK-LC- 1, K- Ras / m, LAGE-A1, LDLR-FUT, MAGE-A1, MAGE-A2, MAGE-A3, MAGE-A4, MAGE-A6, MAGE-A9, MAGE-A10, MAGE-A12, MAGE-B1, MAGE-B2, MAGE-B3, MAGE-B4, MAGE-B5, MAGE-B6, MAGE-B10, MAGE-B1 6, MAGE-B1 7, MAGE-C1, MAGE-C2, MAGE-C3, MAGE- Dl, MAGE-D2, MAGE-D4, MAGE-E1, MAGE-E2, MAGE-F1, MAGE-H I, MAGEL2, mammaglobin A, MART- 1 / melan-A, MART-2, MART-2 / m, matrix protein 22, MCI R, M-CSF, ME 1 / m, mesothelin, MG50 / PXDN, MMP1 1, MN / CA IX- antigen, MRP-3, MUC-1, MUC-2, MUM-l / m, MUM-2 / m, MUM-3 / m, myosin class 1 / m, IMA88-A, N- acetylgl ucosaminy transferase- V, Neo-PAP, Neo-PAP / m, NFYC / m, NGEP, NMP22, NPM / ALK, N-Ras / m, NSE, NY-ESO-1, NY-ESO-B, OA1, OFA- iLRP, OGT, OGT / m, OS-9, OS- 9 / m, osteocalcin, osteopontin, pi 5, pl90 minor bcr-abl, p53, p53 / m, PAGE-4, PAI-1, PAI- 2, PAP, PART-1, PATE, PDEF, Pim-1 -Kinase, Pin-1, Pml / PARalpha, POTE, PRAME, PRDX5 / m, prostein, proteinase-3, PSA, PSCA, PSGR, PSM, PSMA, PTPRK / m, RAGE-1, RBAF600 / m, RHAM / CD1 68, RU1, RU2, S-100, SAGE, SART-1, SART-2, SART-3, SCC, SIRT2 / m, Spl 7, SSX-1, SSX-2 / HOM-MEL-40, SSX-4, STAMP-1, STEAP-1, survivin, survivin-2B, SYT-SSX-1, SYT-SSX-2, TA-90, TAG-72, TARP, TEL-AML1, TGFbeta, TGFbetaRII, TGM-4, TPI / m, TRAG- 3, TRG, TRP-1, TRP-2 / 6b, TRP / INT2, TRP-p8, tyrosinase, UPA, VEGFRl, VEGFR-2 / FLK-1, WTl and a immunoglobulin idiotype of a lymphoid blood cell or a T cell receptor idiotype of a lymphoid blood cell, or a homolog, fragment, variant or derivative of any of these tumor antigens; preferably survivin or a homologue thereof, an antigen from the MAGE-family or a binding partner thereof or a fragment, variant or derivative of said tumour antigen.

[0322] Particularly preferred in this context are the tumour antigens NY-ESO-1, 5T4, MAGE-C1, MAGE-C2, Survivin, Muc-1, PSA, PSMA, PSCA, STEAP and PAP, or homologs, fragments, variants or derivatives of any of these tumor antigens.

[0323] The term "pathogenic antigen" refers to antigenic (poly-)peptides or proteins derived from or associated with pathogens, i.e. viruses, microorganisms, or other substances causing infection and typically disease, including, besides viruses, bacteria, protozoa or fungi. In particular, such "pathogenic antigens" may be capable of eliciting an immune response in a subject, preferably a mammalian subject, more preferably a human. Typically, pathogenic antigens may be surface antigens, e.g. (poly-)peptides or proteins (or fragments of proteins, e.g. the exterior portion of a surface antigen) located at the surface of the pathogen (e.g. its capsid, plasma membrane or cell wall).

[0324] Accordingly, in some preferred embodiments, the artificial nucleic acid (RNA) molecule may encode in its at least one coding region at least one pathogenic antigen selected from a bacterial, viral, fungal or protozoal antigen. The encoded (poly-)peptide or protein may consist or comprise of a pathogenic antigen or a fragment, variant or derivative thereof.

[0325] Pathogenic antigens may preferably be selected from antigens derived from the pathogens Acinetobacter baumannii, Anaplasma genus, Anaplasma phagocytophi lum, Ancylostoma braziliense, Ancylostoma duodenale, Arcanobacterium haemolyticum, Ascaris lumbricoides, Aspergillus genus, Astroviridae, Babesia genus, Bacillus anthracis, Bacillus cereus, Bartonella henselae, BK virus, Blastocystis hominis, Blastomyces dermatitidis, Bordetella pertussis, Borrelia burgdorferi, Borrelia genus, Borrelia spp, Brucella genus, Brugia malayi, Bunyaviridae family, Burkholderia cepacia and other Burkholderia species, Burkholderia mallei, Burkholderia pseudomallei, Caliciviridae family, Campylobacter genus, Candida albicans, Candida spp, Chlamydia trachomatis, Chlamydophila pneumoniae, Chlamydophila psittaci, QD prion, Clonorchis sinensis, Clostridium botulinum, Clostridium diffici le, Clostridium perfri ngens, Clostridium perfringens, Clostridium spp, Clostridium tetani, Coccidioides spp, coronaviruses, Corynebacterium diphtheriae, Coxiella burnetii, Crimean-Congo haemorrhagic fever virus, Cryptococcus neoformans, Cryptosporidium genus, Cytomegalovirus (CMV), Dengue viruses (DEN-1 , DEN-2, DEN-3 and DEN-4), Dientamoeba fragi lis, Ebolavirus (EBOV), Echinococcus genus, Ehrlichia chaffeensis, Ehrlichia ewingii, Ehrlichia genus, Entamoeba histolytica, Enterococcus genus, Enterovirus genus, Enteroviruses, mainly Coxsackie A virus and Enterovirus 71 (EV71 ), Epidermophyton spp, Epstei n-Barr Virus (EBV), Escherichia coli 01 57: H7, 01 1 1 and 01 04:H4, Fasciola hepatica and Fasciola gigantica, FFI prion, Filarioidea superfami ly, Flaviviruses, Francisella tularensis, Fusobacterium genus, Geotrichum candidum, Giardia intestinalis, Gnathostoma spp, GSS prion, Guanarito virus, Haemophilus ducreyi, Haemophi lus influenzae, Helicobacter pylori, Henipavirus (Henclra virus Nipah virus), Hepatitis A Virus, Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), Hepatitis D Virus, Hepatitis E Virus, Herpes simplex virus 1 and 2 (HSV-1 and HSV-2), Histoplasma capsulatum, HIV (Human immunodeficiency virus), Hortaea werneckii, Human bocavirus (HBoV), Human herpesvirus 6 (HHV-6) and Human herpesvirus 7 (HHV-7), Human metapneumovirus (hMPV), Human papillomavirus (HPV), Human parainfluenza viruses (HPIV), Japanese encephalitis virus, JC virus, Junin virus, Kingella kingae, Klebsiella granulomatis, Kuru prion, Lassa virus, Legionella pneumophila, Leishmania genus, Leptospira genus, Listeria monocytogenes, Lymphocytic choriomeningitis virus (LCMV), Machupo virus, Malassezia spp, Marburg virus, Measles virus, Metagonimus yokagawai, Microsporidia phylum, Molluscum contagiosum virus (MCV), Mumps virus, Mycobacterium leprae and Mycobacterium lepromatosis, Mycobacterium tuberculosis, Mycobacterium ulcerans, Mycoplasma pneumoniae, Naegleria fo leri, Necator americanus, Neisseria gonorrhoeae, Neisseria meningitidis, Nocardia asteroides, Nocardia spp, Onchocerca volvulus, Orientia tsutsugamushi, Orthomyxoviridae family (Influenza), Paracoccidioides brasiliensis, Paragonimus spp, Paragonimus westermani, Parvovirus B19, Pasteurella genus, Plasmodium genus, Pneumocystis jirovecii, Poliovirus, Rabies virus, Respiratory syncytial virus (RSV), Rhinovirus, rhinoviruses, Rickettsia akari, Rickettsia genus, Rickettsia prowazekii, Rickettsia rickettsii, Rickettsia typhi, Rift Valley fever virus, Rotavirus, Rubella virus, Sabia virus, Salmonella genus, Sarcoptes scabiei, SARS coronavirus, Schistosoma genus, Shigella genus, Sin Nombre virus, Hantavirus, Sporothrix schenckii, Staphylococcus genus, Staphylococcus genus, Streptococcus agalactiae, Streptococcus pneumoniae, Streptococcus pyogenes, Strongyloides stercoralis, Taenia genus, Taenia solium, Tick-borne encephalitis virus (TBEV), Toxocara canis or Toxocara cati, Toxoplasma gondii, Treponema pallidum, Trichineila spiralis, Trichomonas vaginalis, Trichophyton spp, Trichuris trichiura, Trypanosoma brucei, Trypanosoma cruzi, Ureaplasma urealyticum, Varicella zoster virus (VZV), Varicella zoster virus (VZV), Variola major or Variola minor, vCJD prion, Venezuelan equine encephalitis virus, Vibrio cholerae, West Nile virus, Western equine encephalitis virus, Wuchereria bancrofti, Yellow fever virus, Yersinia enterocolitica, Yersinia pestis, and Yersinia pseudotuberculosis, or an isoform, homolog, fragment, variant or derivative of any of these proteins.

[0326] Further preferred pathogenic antigens may be derived from Influenza virus, respiratory syncytial virus (RSV), Herpes simplex virus (HSV), human Papilloma virus (HPV), Human immunodeficiency virus (HIV), Plasmodium, Staphylococcus aureus, Dengue virus, Chlamydia trachomatis, Cytomegalovirus (CMV), Hepatitis B virus (HBV), Mycobacterium tuberculosis, Rabies virus, and Yellow Fever Virus, or an isoform, homolog, fragment, variant or derivative of any of these proteins.

[0327] Further preferred pathogenic antigens may be derived from Agrobacterium tumefaciens, Ajellomyces dermatitidis ATCC 60636, Alphapapillomavirus 10, Andes orthohantavirus, Andes virus CHI-7913, Aspergillus terreus NIH2624, Avian hepatitis E virus, Babesia microti, Bacillus anthracis, Bacteria, Betacoronavirus England 1, Blattella germanica, Bordetella pertussis, Borna disease virus Giessen strain He / 80, Borrelia burgdorferi B31, Borrelia burgdorferi CA12, Borrelia burgdorferi N40, Borrelia burgdorferi ZS7, Borrelia garinii IP90, Borrelia hermsii, Borreliella afzelii, Borreliella burgdorferi, Borreliella garinii, Bos taurus, Brucella melitensis, Brugia malayi, Bundibugyo ebolavirus, Burkholderia pseudomallei, Burkholderia pseudomallei K96243, Campylobacter jejuni, Campylobacter upsaliensis, Candida albicans, Cavia porcellus, Chikungunya virus, Chikungunya virus MY / 08 / 065, Chikungunya virus Singapore / 11 / 2008, Chikungunya virus strain LR2006_OPY1 IMT / Reunion Island / 2006, Chikungunya virus strain S27-African prototype, Chlamydia pneumoniae, Chlamydia trachomatis, Chlamydia trachomatis Serovar D, Chlamydiae, Clostridioides difficile, Clostridium difficile BI / NAP1 / 027, Clostridium tetani, Convict Creek 107 virus, Corynebacterium diphtheriae, Cowpox virus (Brighton Red) White-pock, Coxsackievirus A16, Coxsackievirus A9, Coxsackievirus Bl, Coxsackievirus B2, Coxsackievirus B3, Coxsackievirus B4, Crimean-Congo hemorrhagic fever orthonairovirus, Cryptosporidium parvum, Dengue virus, Dengue virus 1, Dengue virus 1 Nauru / West Pac / 1974, Dengue virus 1 PVP159, Dengue virus 1 Singapore / S275 / 1990, Dengue virus 2, Dengue virus 2 D2 / SG / 05K4155DK1 / 2005, Dengue virus 2 Jamaica / 1409 / 1983, Dengue virus 2 Puerto Rico / PR159-Sl / 1969, Dengue virus 2 strain 43, Dengue virus 2 Thailand / 16681 / 84, Dengue virus 2 Thailand / NGS-C / 1944, Dengue virus 3, Dengue virus 4, Dengue virus 4 Dominica / 814669 / 1981, Dengue virus 4 Thailand / 0348 / 1991, Dengue virus type 1 Hawaii, Ebola virus - ayinga, Zaire, 1976, Ebolavirus, Echinococcus granulosus, Echinococcus multilocularis, Echovirus Ell, Echovirus E9, Ehrlichia canis str. Jake, Ehrlichia chaffeensis, Ehrlichia chaffeensis str. Arkansas, Entamoeba histolytica, Entamoeba histolytica YS-27, Enterococcus faecium, Enterovirus A, Enterovirus A71, Enterovirus C, Escherichia coli, Fasciola gigantica, Fasciola hepatica, Four Corners hantavirus, Francisella tularensis, Francisella tularensis subsp. holarctica LVS, Francisella tularensis subsp. tularensis SCHU S4, Gambierdiscus toxicus, GB virus C, Glossina morsitans morsitans, Gnathostoma binucleatum, Gpl60, H1N1 subtype, H5N1 subtype, Haemophilus influenzae NTHi 1128, Haemophilus influenzae Serotype B, Haemophilus influenzae Subtype 1H, Hantaan orthohantavirus, Hantaan virus 76-118, HBV genotype D, Helicobacter pylori, Helicobacter pylori 26695, Heligmosomoides polygyrus, Hepatitis B virus, Hepatitis B virus adr4, Hepatitis B virus ayw / France / Tiollais / 1979, Hepatitis B virus genotype D, Hepatitis B virus subtype adr, Hepatitis B virus subtype adw, Hepatitis B virus subtype adw2, Hepatitis B virus subtype adyw, Hepatitis B virus subtype AYR, Hepatitis B virus subtype ayw, Hepatitis C virus, Hepatitis C virus (isolate 1), Hepatitis C virus (isolate BK), Hepatitis C virus (isolate Conl), Hepatitis C virus (isolate Glasgow), Hepatitis C virus (isolate H), Hepatitis C virus (isolate H77), Hepatitis C virus (isolate HC-G9), Hepatitis C virus (isolate HCV-K3a / 650), Hepatitis C virus (isolate Japanese), Hepatitis C virus (isolate JK049), Hepatitis C virus (isolate NZLl), Hepatitis C virus (isolate Taiwan), Hepatitis C virus genotype 1, Hepatitis C virus genotype 2, Hepatitis C virus genotype 3, Hepatitis C virus genotype 4, Hepatitis C virus genotype 5, Hepatitis C virus genotype 6, Hepatitis C virus HCT18, Hepatitis C virus HCV-KF, Hepatitis C virus isolate HC-J1, Hepatitis C virus isolate HC-J6, Hepatitis C virus isolate HC-J8, Hepatitis C virus JFH-1, Hepatitis C virus subtype la, Hepatitis C virus subtype la Chiron Corp., Hepatitis C virus subtype lb, Hepatitis C virus subtype lb AD78, Hepatitis C virus subtype lb isolate BE-11, Hepatitis C virus subtype lb JK1, Hepatitis C virus subtype 2a, Hepatitis C virus subtype 2b, Hepatitis C virus subtype 3a, Hepatitis C virus subtype 5a, Hepatitis C virus subtype 6a, Hepatitis delta virus, Hepatitis delta virus TW2667, Hepatitis E virus, Hepatitis E virus (strain Burma), Hepatitis E virus (strain Mexico), Hepatitis E virus SAR-55, Hepatitis E virus type 3 Kernow-Cl, Hepatitis E virus type 4 JAK-Sai, Hepatovirus A, Heron hepatitis B virus, Herpes simplex virus (type 1 / strain 17), Herpesviridae, HIV- 1 CRF01_AE, HIV-1 group 0, HIV-1 M:A, HIV-1 M:B, HIV-1 M:B_89.6, HIV-1 M:B_HXB2R, HIV-1 M:B_MN, HIV-1 M:C, HIV-

[0328] 1 M:CRF01_AE, HIV-1 M:G, HIV-1 O_ANT70, Human adenovirus 11, Human adenovirus 2, Human adenovirus 40, Human adenovirus 5, Human alphaherpesvirus 1, Human alphaherpesvirus 2, Human alphaherpesvirus 3, Human betaherpesvirus 5, Human betaherpesvirus 6B, Human bocavirus 1, Human bocavirus 2, Human bocavirus 3, Human coronavirus 229E, Human coronavirus OC43, Human endogenous retrovirus, Human endogenous retrovirus H, Human endogenous retrovirus K, Human enterovirus 71 Subgenogroup C4, Human gammaherpesvirus 4, Human gammaherpesvirus 8, Human hepatitis A virus Hu / Australia / HM175 / 1976, Human herpesvirus 1 strain KOS, Human herpesvirus 2 strain 333, Human herpesvirus

[0329] 2 strain HG52, Human herpesvirus 3 H-551, Human herpesvirus 3 strain Oka vaccine, Human herpesvirus 4 strain B95-8, Human herpesvirus 4 type 1, Human herpesvirus 4 type 2, Human herpesvirus 5 strain AD169, Human herpesvirus 5 strain Towne, Human herpesvirus 6 (strain Uganda-1102), Human herpesvirus 7 strain JI, Human immunodeficiency virus 1, Human immunodeficiency virus 2, Human immunodeficiency virus type 1 (isolate YU2), Human immunodeficiency virus type 1 (JRCSF ISOLATE), Human immunodeficiency virus type 1 (NEW YORK-5 ISOLATE), Human immunodeficiency virus type 1 (SF162 ISOLATE), Human immunodeficiency virus type 1 (SF33 ISOLATE), Human immunodeficiency virus type 1 BH10, Human metapneumovirus, Human orthopneumovirus, Human papillomavirus, Human papillomavirus type 11, Human papillomavirus type 16, Human papillomavirus type 18, Human papillomavirus type 29, Human papillomavirus type 31, Human papillomavirus type 33, Human papillomavirus type 35, Human papillomavirus type 39, Human papillomavirus type 44, Human papillomavirus type 45, Human papillomavirus type 51, Human papillomavirus type 52, Human papillomavirus type 58, Human papillomavirus type 59, Human papillomavirus type 6, Human papillomavirus type 68, Human papillomavirus type 6b, Human papillomavirus type 73, Human parainfluenza 3 virus (strain NIH 47885), Human parechovirus 1, Human parvovirus 4, Human parvovirus B19, Human poliovirus 1, Human poliovirus 1 Mahoney, Human poliovirus 3, Human poiyomavirus 1, Human respiratory syncytial virus (strain RSB1734), Human respiratory syncytial virus (strain RSB6190), Human respiratory syncytial virus (strain RSB6256), Human respiratory syncytial virus (strain RSB642), Human respiratory syncytia! virus (subgroup B / strain 18537), Human respiratory syncytial virus A, Human respiratory syncytial virus A strain Long, Human respiratory syncytial virus A2, Human respiratory syncytial virus S2, Human respirovirus 3, Human rhinovirus A89, Human rotavirus A, Human T-cell lymphotrophic virus type 1 (Caribbean isolate), Human T-cell lymphotrophic virus type 1 (isolate MT-2), Human T-cell lymphotrophic virus type 1 (strain ATK), Human T- cell lymphotropic virus type 1 (african isolate), Human T-lymphotropic virus 1, Human T-lymphotropic virus 2, Influenza A virus, Influenza A virus (A / Anhui / 1 / 2005(H5N1)), Influenza A virus (A / Anhui / PA-1 / 2013(H7N9)), Influenza A virus (A / Argentina / 3779 / 94(H3N2)), Influenza A virus (A / Auckland / 1 / 2009(H1N1)), Influenza A virus (A / Bar-headed Goose / Qinghai / 61 / 05(H5N1)), Influenza A virus (A / Brevig Mission / l / 1918(HlNl)), Influenza A virus (A / California / 04 / 2009(H1N1)), Influenza A virus (A / California / 07 / 2009(H1 1)), Influenza A virus (A / California / 08 / 2009(H1N1)), Influenza A virus (A / California / I0 / 1978(H1N1)), Influenza A virus (A / Christchurch / 2 / 1988(H3N2)), Influenza A virus (A / Cordoba / 3278 / 96(H3N2)), Influenza A virus (A / France / 75 / 97(H3N2)), Influenza A virus (A / Fujian / 411 / 2002(H3N2)), Influenza A virus (A / Hong Kong / Ol / 2009(H1N1)), Influenza A virus (A / Hong Kong / l / 1968(H3N2)), Influenza A virus (A / Indonesia / CDC699 / 2006(H5N1)), Influenza A virus (A / Iran / 1 / 1957(H2N2)), Influenza A virus (A / Memphis / 13 / 1978(H1N1)), Influenza A virus (A / Memphis / 4 / 1980(H3N2)), Influenza A virus (A / Nanchang / 58 / 1993(H3N2)), Influenza A virus (A / New York / 232 / 2004(H3N2)), Influenza A virus (A / New_York / 15 / 94(H3N2)), Influenza A virus (A / New_York / 17 / 94(H3N2)), Influenza A virus (A / Ohio / 3 / 95(H3N2)), Influenza A virus (A / Otago / 5 / 2005(HlNl)), Influenza A virus (A / Puerto Rico / 8 / 1934(HlNl)), Influenza A virus (A / Shangdong / 5 / 94(H3N2)), Influenza A virus (A / Solomon Islands / 3 / 2006 (Egg passage)(HlNl)), Influenza A virus (A / South Carolina / l / 1918(HlNl)), Influenza A virus (A / s ine / Hong Kong / 126 / 1982(H3N2)), Influenza A virus (A / swine / Iowa / 15 / 1930(HlNl)), Influenza A virus (A / Sydney / 05 / 97-like(H3N2)), Influenza A virus (A Texas / 1 / 1977(H3N2)), Influenza A virus (A / Udorn / 307 / 1972(H3N2)), Influenza A virus (A / Uruguay / 716 / 2007(H3N2)), Influenza A virus (A / USSR / 26 / 1985(H3N2)), Influenza A virus (A / Viet Nam / 1203 / 2004(H5N1)), Influenza A virus (A / Vietnam / 1194 / 2004(H5Nl)), Influenza A virus (A / Wellington / 75 / 2006(HllMl)), Influenza A virus (A / Wilson- Smith / 1933(H1N1)), Influenza A virus (A / Wuhan / 359 / 1995(H3N2)), Influenza A virus (STRAIN A / EQUINE / NEW MARKET / 76), Influenza B virus, Japanese encephalitis virus, Japanese encephalitis virus strain Nakayama, Japanese encephalitis virus Vellore P20778, JC poiyomavirus, Junin mammarenavirus, Klebsiella pneumoniae, Kumlinge virus, Lake Victoria marburgvirus - Popp, Lassa mammarenavirus, Lassa virus Josiah, Leishmania, Leishmania aethiopica, Leishmania braziliensis, Leishmania braziliensis MHOM / BR / 75 / M2904, Leishmania chagasi, Leishmania donovani, Leishmania infantum, Leishmania major, Leishmania major strain Friedlin, Leishmania panamensis, Leishmania pifanoi, Leptospira interrogans, Leptospira interrogans serovar Australis, Leptospira interrogans serovar Copenhagen!, Leptospira interrogans serovar Copenhagen! str. Fiocruz Ll-130, Leptospira interrogans serovar Lai, Leptospira interrogans serovar Lai str. HY-1, Leptospira interrogans serovar Pomona, Little cherry virus 1, Lymphocytic choriomeningitis mammarenavirus, Measles morbillivirus, Measles virus strain Edmonston, Merkel cell poiyomavirus, Mobala mammarenavirus, Modified Vaccinia Ankara virus, Moraxella catarrhalis 035E, Mupapillomavirus 1, Mus musculus, Mycobacterium, Mycobacterium abscessus, Mycobacterium avium, Mycobacterium avium serovar 8, Mycobacterium avium subsp. paratuberculosis, Mycobacterium bovis AN5, Mycobacterium bovis BCG, Mycobacterium bovis BCG str. Pasteur 1173P2, Mycobacterium fortuitum subsp. fortuitum, Mycobacterium gilvum, Mycobacterium intracellulare, Mycobacterium kansasii, Mycobacterium leprae, Mycobacterium leprae TN, Mycobacterium marinum, Mycobacterium neoaurum, Mycobacterium phlei, Mycobacterium smegmatis, Mycobacterium tuberculosis, Mycobacterium tuberculosis CDC1551, Mycobacterium tuberculosis H37Ra, Mycobacterium tuberculosis H37Rv, Mycobacterium ulcerans, Mycoplasma pneumoniae, Mycoplasma pneumoniae FH, Mycoplasma pneumoniae M129, Necator americanus, Neisseria gonorrhoeae, Neisseria meningitidis serogroup B H44 / 76, Nipah henipavirus, Norovirus genogroup 2 Camberwell 1890, Onchocerca volvulus, Orientia tsutsugamushi, Oryctolagus cuniculus, Pan troglodytes, Paracoccidioides brasiliensis, Paracoccidioides brasiliensis B339, Plasmodium falciparum, Plasmodium falciparum 3D7, Plasmodium falciparum 7G8, Plasmodium falciparum FC27 / Papua New Guinea, Plasmodium falciparum FCR-3 / Gambia, Plasmodium falciparum isolate WELLCOME, Plasmodium falciparum Kl, Plasmodium falciparum LE5, Plasmodium falciparum Mad20 / Papua New Guinea, Plasmodium falciparum NF54, Plasmodium falciparum Palo Alto / Uganda, Plasmodium falciparum RO-33, Plasmodium reichenowi, Plasmodium vivax, Plasmodium vivax NK, Plasmodium vivax Sal-1, Plasmodium vivax strain Belem, Plasmodium vivax-like sp., Porphyromonas gingivalis, Porphyromonas gingivalis 381, Porphyromonas gingivalis OMZ 409, Prevotella sp. oral taxon 472 str. F0295, Pseudomonas aeruginosa, Puumala orthohantavirus, Puumala virus (strain Umea / hu), Puumala virus sotkamo / v-2969 / 81, Pythium insidiosum, Ravn virus - Ravn, Kenya, 1987, Respiratory syncytial virus, Rhodococcus fascia ns, Rhodococcus hoagii, Rubella virus, Rubella virus strain M33, Rubella virus strain Therien, Rubella virus vaccine strain RA27 / 3, Saccharomyces cerevisiae, Saimiriine gammaherpesvirus 2, Salmonella enterica subsp. enterica serovar Typhi, Salmonella 'group A', Salmonella 'group D', Salmonella sp. 'group B', Sapporo rat virus, SARS coronavirus, SARS coronavirus BJ01, SARS coronavirus TJF, SARS coronavirus Tor2, SARS coronavirus Urbani, Schistosoma, Schistosoma japonicum, Schistosoma mansoni, Schistosoma mansoni Puerto Rico, Sin Nombre orthohantavirus, Sindbis virus, Staphylococcus aureus, Staphylococcus aureus subsp. aureus COL, Staphylococcus aureus subsp. aureus MRSA252, Streptococcus, Streptococcus mutans, Streptococcus mutans MT 8148, Streptococcus oralis, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus pyogenes serotype M24, Streptococcus pyogenes serotype M3 D58, Streptococcus pyogenes serotype M5, Streptococcus pyogenes serotype M6, Streptococcus sp. 'group A', Taenia crassiceps, Taenia saginata, Taenia solium, Tick-borne encephalitis virus, Toxocara canis, Toxoplasma gondii, Toxoplasma gondii ME49, Toxoplasma gondii RH, Toxoplasma gondii type I, Toxoplasma gondii type II, Toxoplasma gondii type III, Toxoplasma gondii VEG, Treponema pallidum, Treponema pallidum subsp. pallidum str. Nichols, Trichomonas vaginalis, Triticum aestivum, Trypanosoma brucei brucei, Trypanosoma brucei gambiense, Trypanosoma cruzi, Trypanosoma cruzi Dm28c, Trypanosoma cruzi strain CL Brener, Vaccinia virus, Vesicular stomatitis virus, Vibrio cholerae, West Nile virus, West Nile virus NY-99, Wuchereria bancrofti, Yellow fever virus 17D / Tiantan, Yersinia enterocolitica, Zaire ebolavirus, Zika virus, or an isoform, homolog, fragment, variant or derivative of any of these proteins.

[0330] Artificial nucleic acid molecules of the invention encoding preferred influenza-derived pathogenic antigens may preferably comprise a coding region comprising or consisting of a nucleic acid sequence according to any one of the SEQ ID NOs as shown in Fig. 1, Fig. 2, Fig. 3 or Fig. 4 or respectively Table 1, Table 2, Table 3 or Table 4 of international patent application PCT / EP2017 / 060663, or a fragment or variant of any of these sequences, in particular a nucleic acid sequence having a sequence identity of at least 50%, 60%, 70%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%, preferably at least 80% to any of these sequences. In this context, the disclosure of PCT / EP2017 / 060663 is incorporated herein by reference.

[0331] Artificial nucleic acid molecules of the invention encoding further preferred influenza-derived pathogenic antigens may preferably comprise a coding region comprising or consisting of a nucleic acid sequence according to any one of the SEQ ID NOs as shown in Fig. 20, Fig. 21, Fig. 22, or Fig. 23 or respectively Table 1, Table 2, Table 3 or Table 4 of international patent application PCT / EP2017 / 064066, or a fragment or variant of any of these sequences, in particular a nucleic acid sequence having a sequence identity of at least 50%, 60%, 70%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%, preferably at least 80% to any of these sequences. In this context, the disclosure of PCT / EP2017 / 064066 is incorporated herein by reference.

[0332] Artificial nucleic acid molecules of the invention encoding preferred rabies virus-derived pathogenic antigens may preferably comprise a coding region comprising or consisting of a nucleic acid sequence according to SEQ ID NO: 24 or SEQ ID NO: 25 of international patent application WO 2015 / 024665 Al, or a fragment or variant of any of these sequences, in particular a nucleic acid sequence having a sequence identity of at least 50%, 60%, 70%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%, preferably at least 80% to any of these sequences. In this context, the disclosure of WO 2015 / 024665 Al is incorporated herein by reference.

[0333] Artificial nucleic acid molecules of the invention encoding further preferred rabies virus-derived pathogenic antigens may preferably comprise a coding region comprising or consisting of a nucleic acid sequence according to SEQ ID NO: 24 or Table 5 of international patent application PCT / EP2017 / 064066, or a fragment or variant of any of these sequences, in particular a nucleic acid sequence having a sequence identity of at least 50%, 60%, 70%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%, preferably at least 80% to any of these sequences. In this context, the disclosure of PCT / EP2017 / 064066is incorporated herein by reference.

[0334] Artificial nucleic acid molecules of the invention encoding preferred RSV-derived pathogenic antigens may preferably comprise a coding region comprising or consisting of a nucleic acid sequence according to any one of SEQ ID NOs: 31 to 35 of international patent application WO 2015 / 024668 A2, or a fragment or variant of any of these sequences, in particular a nucleic acid sequence having a sequence identity of at least 50%, 60%, 70%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%, preferably at least 80% to any of these sequences. In this context, the disclosure of WO 2015 / 024668 A2 is incorporated herein by reference.

[0335] Artificial nucleic acid molecules of the invention encoding preferred Ebola or Marburgvirus-derived pathogenic antigens may preferably comprise a coding region comprising or consisting of a nucleic acid sequence according to any one of SEQ ID NOs: 20 to 233 of international patent application WO 2016 / 097065 Al, or a fragment or variant of any of these sequences, in particular a nucleic acid sequence having a sequence identity of at least 50%, 60%, 70%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%, preferably at least 80% to any of these sequences. In this context, the disclosure of WO 2016 / 097065 Al is incorporated herein by reference.

[0336] Artificial nucleic acid molecules of the invention encoding preferred Zikavirus-derived pathogenic antigens may preferably comprise a coding region comprising or consisting of a nucleic acid sequence according to any one of SEQ ID NOs: 1 to 11759 or Table 1, Table 1A, Table 2, Table 2A, Table 3, Table 3A, Table 4, Table 4A, Table 5, Table 5A, Table 6, Table 6A, Table 7, Table 8, or Table 14 of international patent application WO 2017 / 140905 Al, or a fragment or variant of any of these sequences, in particular a nucleic acid sequence having a sequence identity of at least 50%, 60%, 70%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%, preferably at least 80% to any of these sequences. In this context, the disclosure of WO 2017 / 140905 Al is incorporated herein by reference. Artificial nucleic acid molecules of the invention encoding preferred Norovirus-derived pathogenic antigens may preferably comprise a coding region comprising or consisting of a nucleic acid sequence according to any one of SEQ ID NOs: 1 to 39746 or Table 1 of international patent application PCT / EP2017 / 060673, or a fragment or variant of any of these sequences, in particular a nucleic acid sequence having a sequence identity of at least 50%, 60%, 70%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%, preferably at least 80% to any of these sequences. In this context, the disclosure of PCT / EP2017 / 060673 is incorporated herein by reference.

[0337] Artificial nucleic acid molecules of the invention encoding preferred Rotavirus-derived pathogenic antigens may preferably comprise a coding region comprising or consisting of a nucleic acid sequence according to any one of SEQ ID NOs: 1 to 3593 or Tables 1-20 of international patent application WO 2017 / 081110 Al, or a fragment or variant of any of these sequences, in particular a nucleic acid sequence having a sequence identity of at least 50%, 60%, 70%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%, preferably at least 80% to any of these sequences. In this context, the disclosure of WO 2017 / 081110 Al is incorporated herein by reference.

[0338] The term "autoantigen" refers to an endogenous "self-"antigen that -despite being a normal body constituent- induces an autoimmune reaction in the host. In the context of the present invention, autoantigens are preferably of human origin. The provision of an artificial nucleic acid (RNA) molecule encoding an antigenic (poly-)peptide or protein derived from an autoantigen can, for instance, be used to induce immune tolerance towards said autoantigen. Exemplary autoantigens in the context of the present invention include, without limitation, autoantigen derived or selected from 60 kDa chaperonin 2, Lipoprotein LpqH, Melanoma antigen recognized by T-cells 1, MHC class I polypeptide-related sequence A, Parent Protein, Structural polyprotein, Tyrosinase, Myelin proteolipid protein, Epstein-Barr nuclear antigen 1, Envelope glycoprotein GP350, Genome polyprotein, Collagen alpha-l(II) chain, Aggrecan core protein, Melanocyte-stimulating hormone receptor, Acetylcholine receptor subunit alpha, 60 kDa heat shock protein, mitochondrial, Histone H4, Myosin- 11, Glutamate decarboxylase 2, 60 kDa chaperonin, PqqC-like protein, Thymosin beta-10, Myelin basic protein, Epstein- Barr nuclear antigen 4, Melanocyte protein PMEL, HLA class II histocompatibility antigen, DQ beta 1 chain, Latent membrane protein 2, Integrin beta-3, Nucleoprotein, 60S ribosomal protein L10, Protein BOLF1, 60S acidic ribosomal protein P2, Latent membrane protein 1, Collagen alpha-2(VI) chain, Exodeoxyribonuclease V, Gamma, Trans-activator protein BZLF1, S-arrestin, HLA class I histocompatibility antigen, A-3 alpha chain, Protein CT_579, Matrin-3, Envelope glycoprotein B, ATP-dependent zinc metalloprotease FtsH, Ul small nuclear ribonucleoprotein 70 kDa, CD48 antigen, Tubulin beta chain, Actin, cytoplasmic 1, Epstein-Barr nuclear antigen 3, NEDD4 family-interacting protein 1, 60S ribosomal protein L28, Immediate-early protein 2, Insulin, isoform 2, Keratin, type II cytoskeletal 3, Matrix protein 1, Histone H2A.Z, mRNA export factor ICP27 homolog, Small nuclear ribonucleoprotein-associated proteins B and B', Large cysteine-rich periplasmic protein OmcB, Smoothelin, Small nuclear ribonucleoprotein Sm Dl, Acetylcholine receptor subunit epsilon, Invasin repeat family phosphatase, Alpha-crystallin B chain, HLA class II histocompatibility antigen, DRB1-13 beta chain, HLA class II histocompatibility antigen, DRB1-4 beta chain, Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex, mitochondrial, Keratin, type I cytoskeletal 18, Epstein-Barr nuclear antigen 6, Protein Tax-1, Vimentin, Keratin, type I cytoskeletal 16, Keratin, type I cytoskeletal 10, HLA class I histocompatibility antigen, B- 27 alpha chain, Thyroglobulin, Acetylcholine receptor subunit gamma, Chaperone protein DnaK, Protein U24, Na(+)- translocating NADH-quinone reductase subunit A, 65 kDa phosphoprotein, Probable ATP-dependent Clp protease ATP- binding subunit, Probable outer membrane protein PmpC, Heat shock 70 kDa protein IB, Hemagglutinin, Tetanus toxin, Enolase, Ras-associated and pleckstrin homology domains-containing protein 1, Keratin, type II cytoskeletal 7, Myosin-9, Histone Hl-like protein Hcl, Envelope glycoprotein gpl60, Urease subunit beta, Vasoactive intestinal polypeptide receptor 1, Viral interleukin-10 homolog, Histone H3.3, Replication protein A 32 kDa subunit, Probable outer membrane protein PmpD, Insulin-2, L-dopachrome tautomerase, Keratin, type I cytoskeletal 9, Envelope glycoprotein H, DNA polymerase catalytic subunit, Beta-2-glycoprotein 1, Envelope glycoprotein gp62, Serum albumin, Major DNA-binding protein, HLA class I histocompatibility antigen, A-2 alpha chain, Myeloblasts, POTE ankyrin domain family member I, Protein E7, Predicted Efflux Protein, Replication and transcription activator, Gag-Pro-Pol polyprotein, Capsid protein VP26, Major capsid protein, Apoptosis regulator BHRF1, Epstein-Barr nuclear antigen 2, HLA class I histocompatibility antigen, B-7 alpha chain, Calreticulin, Gamma-secretase C-terminal fragment 59, Insulin, Glucose-6-phosphatase 2, Islet amyloid polypeptide, Receptor-type tyrosine-protein phosphatase N2, Receptor-type tyrosine-protein phosphatase-like N, Islet cell autoantigen 1, Bos d 6, Glutamate decarboxylase 1, 60S ribosomal protein L29, 28S ribosomal protein S31, mitochondrial, HLA class II histocompatibility antigen, DRB1-16 beta chain, Collagen alpha-3(IV) chain, Glucose-6-phosphatase, Glucose-6- phosphatase 3, Collagen alpha-5(IV) chain, Protein Nef, Glial fibrillary acidic protein, Fibrillin-1, Tenascin, Stromelysin-1, Interstitial collagenase, Calpain-2 catalytic subunit, Chondroitin sulfate proteoglycan 4, Fibrinogen beta chain, Chaperone protein DnaJ, Chitinase-3-like protein 1, Matrix metalloproteinase-16, DNA topoisomerase 1, Follistatin-related protein 1, Ig gamma-1 chain C region, Ig gamma-3 chain C region, Collagen alpha-2(XI) chain, Desmoglein-3, Fibrinogen alpha chain, Filaggrin, T-cell receptor beta chain V region CTL-L17, T-cell receptor beta-1 chain C region, Ig heavy chain V-I region EU, Collagen alpha-l(IV) chain, HLA class I histocompatibility antigen, Cw-7 alpha chain, HLA class I histocompatibility antigen, B-35 alpha chain, HLA class I histocompatibility antigen, B-38 alpha chain, High mobility group protein B2, Ig heavy chain V-II region ARH-77, HLA class II histocompatibility antigen, DR beta 4 chain, Ig kappa chain C region, Alpha-enolase, Lysosomal-associated transmembrane protein 5, HLA class I histocompatibility antigen, B-52 alpha chain, Heterogeneous nuclear ribonucleoproteins A2 / B1, T-cell receptor beta chain V region YT35, Ig gamma-4 chain C region, T-cell receptor beta-2 chain C region, DnaJ homolog subfamily B member 2, DnaJ homolog subfamily A member 1, Ig kappa chain V-IV region Len, Ig heavy chain V-II region OU, Ig kappa chain V-IV region B17, 2',3'-cyclic-nucleotide 3'-phosphodiesterase, Ig heavy chain V-II region MCE, Ig kappa chain V-III region HIC, Ig heavy chain V-II region COR, Myelin-oligodendrocyte glycoprotein, Ig kappa chain V-II region RPMI 6410, Ig kappa chain V-II region GM607, Immunoglobulin lambda-like polypeptide 5, Ig heavy chain V-II region WAH, Biotin-protein ligase, Oligodendrocyte-myelin glycoprotein, Transaldolase, DNA helicase / primase complex-associated protein, Interferon beta, Myelin-associated oligodendrocyte basic protein, Myelin-associated glycoprotein, Fusion glycoprotein F0, Myelin protein P0, Ig lambda chain V-II region MGC, DNA primase, Minor capsid protein L2, Myelin P2 protein, Peripheral myelin protein 22, Retinol-binding protein 3, Butyrophilin subfamily 1 member Al, Alkaline nuclease, Claudin-11, N-acetylmuramoyl-L-alanine amidase CwlH, GTPase Der, Possible transposase, ABC transporter, ATP-binding protein, putative, Collagen alpha-2(IV) chain, Calpastatin, Ig kappa chain V-III region SIE, E3 ubiquitin-protein ligase TRIM68, Glutamate receptor ionotropic, NMDA 2A, Spectrin alpha chain, non-erythrocytic 1, Lupus La protein, Complement Clq subcomponent subunit A, Ul small nuclear ribonucleoprotein A, 60 kDa SS-A / Ro ribonucleoprotein, DNA repair protein XRCC4, Histone H3-like centromeric protein A, Histone H1.4, Putative HTLV-l-related endogenous sequence, HLA class II histocompatibility antigen, DRB1-3 chain, HLA class II histocompatibility antigen, DRBl-1 beta chain, Small nuclear ribonucleoprotein Sm D3, Tumor necrosis factor receptor superfamily member 6, Phosphomannomutase / phosphoglucomutase, Tripartite terminase subunit UL15, Proteasome subunit beta type-3, Proliferating cell nuclear antigen, Inner capsid protein sigma-2, Histone H2B type 1, E3 ubiquitin-protein ligase TRIM21, DNA-directed RNA polymerase II subunit RPB1, X-ray repair cross-complementing protein 6, Ul small nuclear ribonucleoprotein C, Caspase-8, 60S ribosomal protein L7, 5-hydroxytryptamine receptor 4, Small nuclear ribonucleoprotein-associated protein N, Exportin-1, 60S acidic ribosomal protein P0, Neurofilament heavy polypeptide, putative env, T-cell receptor alpha chain C region, T-cell receptor alpha chain V region CTL-L17, RNA polymerase sigma factor SigA, Small nuclear ribonucleoprotein Sm D2, Immunoglobulin iota chain, Ig kappa chain V-III region WOL, Histone H2B type 1-F / J / L, High mobility group protein Bl, X-ray repair cross-complementing protein 5, Muscarinic acetylcholine receptor M3, Major viral transcription factor ICP4, Voltage-dependent P / Q-type calcium channel subunit alpha-lA, Heat shock protein HSP 90-beta, DNA topoisomerase 2-beta, Histone H3.1, Tumor necrosis factor ligand superfamily member 6, Phospho-N-acetylmuramoyl-pentapeptide-transferase, Hemoglobin subunit alpha, Apolipoprotein E, CD99 antigen, ATP synthase subunit beta, mitochondrial, Acetylcholine receptor subunit delta, Acyl-CoA dehydrogenase family member 10, KN motif and ankyrin repeat domain-containing protein 3, SAM and SH3 domain-containing protein 1, Elongation factor 1-alpha 1, GTP-binding nuclear protein Ran, Myosin-7, Sal-like protein 1, IgGFc-binding protein, E3 ubiquitin-protein ligase SIAHl, Muscleblind-like protein 2, Annexin Al, Protein PET117 homolog, mitochondrial, Nuclear ubiquitous casein and cyclin-dependent kinase substrate 1, Pleiotropic regulator 1, NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 3, Guanine nucleotide-binding protein G(o) subunit alpha, Microtubule-associated protein IB, L- serine dehydratase / L-threonine deaminase, Centromere protein J, SH3 and multiple ankyrin repeat domains protein 3, Fumarate hydratase, mitochondrial, Cofilin-1, Rho GTPase-activating protein 9, Phosphatidate cytidylyltransferase 1, Neurofilament light polypeptide, Calsyntenin-1, GPI transamidase component PIG-T, Perilipin-3, Protein unc-13 homolog D, WD40 repeat-containing protein SMU1, Neurofilament medium polypeptide, Protein S100-B, Carboxypeptidase E, Neurexin-2-beta, NAD-dependent protein deacetylase sirtuin-2, Tripartite motif-containing protein 40, Neurexin-l-beta, Annexin All, Hemoglobin subunit beta, Glyceraldehyde-3-phosphate dehydrogenase, Histidine triad nucleotide-binding protein 3, ATP synthase subunit e, mitochondrial, 10 kDa heat shock protein, mitochondrial, Cellular tumor antigen p53, Leukocyte-associated immunoglobulin-like receptor 1, Tubulin alpha-IB chain, Splicing factor, proline- and glutamine-rich, Olfactory receptor 10A4, Histone H2B type 2-F, Calmodulin, RNA-binding protein Raly, Phosphoinositide-3-kinase- interacting protein 1, Alpha-2-macroglobulin, Glycogen phosphorylase, brain form, THO complex subunit 4, Neuroblast differentiation-associated protein AHNAK, Phosphoserine aminotransferase, Mitochondrial folate transporter / carrier, Sentrin-specific protease 3, Cytosolic Fe-S cluster assembly factor NUBP2, Histone deacetylase 7, Serine / threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform, Serine / threonine-protein phosphatase 2A regulatory subunit B" subunit alpha, Gelsolin, Insulin-like growth factor II, Tight junction protein ZO-1, Hsc70-interacting protein, FXYD domain-containing ion transport regulator 6, AP-1 complex subunit mu-1, Syntenin-1, NADH dehydrogenase [ubiquinone] iron-sulfur protein 7, mitochondrial, Low-density lipoprotein receptor, LIM domain transcription factor LM04, Spectrin beta chain, non-erythrocytic 1, ATP-binding cassette sub-family A member 2, NADH dehydrogenase [ubiquinone] 1 subunit C2, SPARC-like protein 1, Electron transfer flavoprotein subunit alpha, mitochondrial, Glutamate dehydrogenase 1, mitochondrial, Complexin-2, Protein-serine O-palmitoleoyltransferase porcupine, Plexin domain-containing protein 2, Threonine synthase-like 2, Testican-2, C-X-C chemokine receptor type 1, Arachidonate 5-lipoxygenase-activating protein, Neuroguidin, Fatty acid 2-hydroxylase, Nuclear factor 1 X-type, LanC-like protein 1, Glutamine synthetase, Lysosome- associated membrane glycoprotein 1, Apolipoprotein A-I, Alpha-adducin, Guanine nucleotide-binding protein G(I) / G(S) / G(T) subunit beta-3, Integral membrane protein GPR137B, Ubiquilin-1, Aldose reductase, Clathrin light chain B, V-type proton ATPase subunit F, Apolipoprotein D, 40S ribosomal protein SA, Bcl-2-associated transcription factor 1, Phosphatidate cytidylyltransferase 2, ATP synthase-coupling factor 6, mitochondrial, Receptor tyrosine-protein kinase erbB- 2, Echinoderm microtubule-associated protein-like 5, Phosphatidylethanolamine-binding protein 1, Myc box-dependent- interacting protein 1, Membrane-associated phosphatidylinositol transfer protein 1, 0S ribosomal protein S29, Small acidic protein, Galectin-3-binding protein, Fatty acid synthase, Baculoviral IAP repeat-containing protein 5, Septin-2, cAMP- dependent protein kinase type II-alpha regulatory subunit, Reelin, Apoptosis facilitator Bcl-2-like protein 14, Staphylococcal nuclease domain-containing protein 1, Methyl-CpG-binding domain protein 2, Transformation / transcription domain- associated protein, Transcription factor HES-1, Protein transport protein Sec238, Paralemmin-2, C-C motif chemokine 15, Sodium / potassium-transporting ATPase subunit alpha-1, Stathmin, Heterogeneous nuclear ribonucleoprotein L-like, Nodal modulator 3, Interferon-induced GTP-binding protein x2, Integrin alpha-D, Low-density lipoprotein receptor-related protein 5-like protein, Macrophage migration inhibitory factor, Ferritin light chain, Dihydropyrimidinase-related protein 2, Neuronal membrane glycoprotein M6-b, ATP-binding cassette sub-family A member 5, Synaptosomal-associated protein 25, Insulin-like growth factor I, Ankyrin repeat domain-containing protein 29, Protein spinster homolog 3, Peflin, Contactin-

[0339] 1, Microfibril-associated glycoprotein 3, von Willebrand factor, Small nuclear ribonucleoprotein G, Interleukin-12 receptor subunit beta-1, Epoxide hydrolase 1, Cytochrome b-cl complex subunit 10, Monoglyceride lipase, Serotransferrin, Alpha- synuclein, Cytosolic non-specific dipeptidase, Transgelin-2, Testisin, Fms-related tyrosine kinase 3 ligand, Noelin-2, Serine / threonine-protein kinase DCLK1, Interferon alpha-2, Acetylcholine receptor subunit beta, Histone H2A type 1, Beta- 2 adrenergic receptor, Putrescine aminotransferase, Interferon alpha-1 / 13, Protein NEDD1, DnaJ homolog subfamily B member 1, Tubulin beta-6 chain, Non-histone chromosomal protein HMG-17, Polyprotein, Exosome component 10, Natural cytotoxicity triggering receptor 3 ligand 1, Gag polyprotein, Band 3 anion transport protein, Protease, Histidine-tRNA ligase, cytoplasmic, Collagen alpha-l(XVII) chain, Envoplakin, Histone H2B type 1-C / E / F / G / I, Diaminopimelate decarboxylase, Histone H2B type 2-E, Cytochrome P450 2D6, Dihydrolipoyilysine-residue succinyltransferase component of 2-oxoglutarate dehydrogenase complex, Histone H2B type 1-H, Thyroid peroxidase, Proline-rich transmembrane protein

[0340] 2, Periplakin, Integrin alpha-6, Dystonin, Desmoplakin, Histone H2B type 1-3, Histone H2B type 1-B, 6,7-dimethyl-8- ribityllumazine synthase, Thyrotropin receptor, Integrin alpha-IIb, Nuclear pore membrane glycoprotein 210, Protein U2, DST protein, Plectin, SII0397 protein, Bos d 10, Outer capsid protein VP4, 5,6-dihydroxyindole-2-carboxyiic acid oxidase, O-phosphoseryl-tRNA(Sec) selenium transferase, ATP-dependent Clp protease proteolytic subunit, Lymphocyte activation gene 3 protein, Phosphoprotein 85, LI protein, Actin, alpha skeletal muscle, Dihydrolipoyl dehydrogenase, Dihydrolipoyilysine-residue succinyltransferase component of 2-oxoglutarate dehydrogenase complex, mitochondrial, Liver carboxylesterase 1, Dihydrolipoyilysine-residue acetyltransferase component of pyruvate dehydrogenase complex, Acetyltransferase component of pyruvate dehydrogenase complex, Pyruvate dehydrogenase protein X component, mitochondrial, Dihydrolipoamide acetyltransferase, Protein disulfide-isomerase A3, Flotillin-2, Beta-galactosidase, TSHR protein, Lipoamide acyltransferase component of branched-chain alpha-keto acid dehydrogenase complex, mitochondrial, Nuclear autoantigen Sp-100, Desmoglein-1, Glucagon receptor, Membrane glycoprotein US8, Sodium / iodide cotransporter, ORF2, Capsid protein, Uncharacterized protein LF3, Formimidoyltransferase-cyclodeaminase, Core-capsid bridging protein, Neurovirulence factor ICP34.5, Probable RNA-binding protein, Cholesterol side-chain cleavage enzyme, mitochondrial, Histone H1.0, Non-histone chromosomal protein HMG-14, Histone H5, 60S acidic ribosomal protein PI, Pyruvate dehydrogenase El component subunit alpha, somatic form, mitochondrial, Leiomodin-1, Uncharacterized protein RP382, Uncharacterized protein U95, (Type IV) pilus assembly protein PilB, 2-succinylbenzoate-CoA ligase, TAZ protein, Tafazzin, Putative lactose-specific phosphotransferase system (PTS), IIBC component, Claudin-17, Pericentriolar material 1 protein, Yop proteins translocation protein L, Laminin subunit alpha-1, A disintegrin and metalloproteinase with thrombospondin motifs 13, Keratin, type I cytoskeletal 14, Coagulation factor VIII, Keratin, type I cytoskeletal 17, Neutrophil defensin 1, Ig alpha-1 chain C region, BRCAl-associated RING domain protein 1, Trinucleotide repeat-containing gene 6A protein, Thrombopoietin, Plasminogen-binding protein PgbA, Steroid 17-alpha-hydroxylase / 17,20 lyase, Nucleolar RNA helicase 2, Histone H2B type 1-N, Steroid 21-hydroxylase, UreB, Melanin-concentrating hormone receptor 1, Blood group Rh(CE) polypeptide, HLA class II histocompatibility antigen, DP beta 1 chain, Platelet glycoprotein lb alpha chain, Muscarinic acetylcholine receptor Ml, Outer capsid glycoprotein VP7, Fibronectin, HLA class I histocompatibility antigen, B-8 alpha chain, AhpC, Cytoskeleton-associated protein 5, Sucrase-isomaltase, intestinal, Leukotriene B4 receptor 2, Glutathione peroxidase 2, Collagen alpha-l(VII) chain, Nucleosome assembly protein l-like 4, Alanine-tRNA ligase, cytoplasmic, Extracellular calcium-sensing receptor, Major centromere autoantigen B, Large tegument protein deneddylase, Blood group Rh(D) polypeptide, Kininogen-1, Peroxiredoxin-2, Ezrin, DNA replication and repair protein RecF, Keratin, type II cytoskeletal 6C, Trigger factor, Serpin B5, Heat shock protein beta-1, Protein-arginine deiminase type-4, Potassium- transporting ATPase alpha chain 1, Potassium-transporting ATPase subunit beta, Forkhead box protein E3, Condensin-2 complex subunit D3, Myotonin-protein kinase, Zinc transporter 8, ABC transporter, substrate-binding protein, putative, Aquaporin-4, Cartilage intermediate layer protein 1, HLA class II histocompatibility antigen, DR beta 5 chain, Small nuclear ribonucleoprotein F, Small nuclear ribonucleoprotein E, Ig kappa chain V-V region L7, Ig heavy chain Mem5, Ig heavy chain V-III region J606, Hemoglobin subunit delta, Collagen alpha-l(XV) chain, 78 kDa glucose-regulated protein, 60S ribosomal protein L22, Alpha-l-acid glycoprotein 1, Malate dehydrogenase, mitochondrial, 60S ribosomal protein L8, Serine protease HTRA2, mitochondrial, 60S ribosomal protein L23a, Complement C3, Collagen alpha-l(XII) chain, Angiotensinogen, Protein S100-A9, Annexin A2, Alpha-actinin-4, HLA class II histocompatibility antigen, DQ alpha 1 chain, Apolipoprotein A-IV, Actin, aortic smooth muscle, HLA class II histocompatibility antigen, DP alpha 1 chain, Creatine kinase B-type, HLA class II histocompatibility antigen, DR beta 3 chain, Histone Hlx, Heterogeneous nuclear ribonucleoprotein U-like protein 2, Basement membrane-specific heparan sulfate proteoglycan core protein, Cadherin-5, 40S ribosomal protein S13, Alpha-l-antitrypsin, Multimerin-2, Centromere protein F, 40S ribosomal protein S18, 40S ribosomal protein S25, Na(+) / H(+) exchange regulatory cofactor NHE-RF1, Actin, cytoplasmic 2, Hemoglobin subunit gamma-1, Hemoglobin subunit gamma-2, Protein NipSnap homolog 3A, Cathepsin D, 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase epsilon-1, 40S ribosomal protein S17, Apolipoprotein B-100, Histone H2B type 1-K, Collagen alpha-l(I) chain, Collagen alpha-2(I) chain, 3-hydroxyacyl-CoA dehydrogenase type-2, 60S ribosomal protein L27, Histone HI.2, Nidogen-2, Cadherin-1, 60S ribosomal protein L27a, HLA class II histocompatibility antigen, DR alpha chain, Dipeptidyl peptidase 1, Ubiquitin-40S ribosomal protein S27a, Citrate synthase, mitochondrial, Taxi-binding protein 1, Myeloperoxidase, Plexin domain-containing protein 1, Glycogen synthase, [Pyruvate dehydrogenase [acetyl-transferring]]-phosphatase 1, mitochondrial, Phorbol-12-myristate-13-acetate-induced protein 1, Peroxiredoxin-5, mitochondrial, 14-3-3 protein zeta / delta, ATP synthase subunit d, mitochondrial, Vitronectin, Lipopolysaccharide-binding protein, Ig heavy chain V-III region GAL, Protein CREG1, 60S ribosomal protein L6, Stabilin-1, Plasma protease CI inhibitor, Ig kappa chain V-III region VG, Inter-alpha-trypsin inhibitor heavy chain H4, Alpha-lB-glycoprotein, Tartrate-resistant acid phosphatase type 5, Sulfhydryl oxidase 1, Complement component C6, Glycogen phosphorylase, muscle form, SH3 domain-binding glutamic acid-rich-like protein 3, Transforming protein RhoA, Albumin, isoform CRA_k, V-type proton ATPase subunit G 1, Flavin reductase (NADPH), Heat shock cognate 71 kDa protein, Lipoprotein lipase, Plasminogen, Annexin, Syntaxin-7, Transmembrane glycoprotein NMB, Coagulation factor XIII A chain, Apolipoprotein A-II, N-acetylglucosamine-6-sulfatase, Complement Clq subcomponent subunit B, Protein S100-A10, Microfibril-associated glycoprotein 4, 72 kDa type IV collagenase, Collagen alpha-l(XI) chain, Cathepsin B, Palmitoyl-protein thioesterase 1, Macrosialin, Histone Hl.l, Histone HI.5, Fibromodulin, Thrombospondin-1, Rho GDP-dissociation inhibitor 2, Alpha-galactosidase A, Superoxide dismutase [Cu-Zn], HLA class I histocompatibility antigen, alpha chain E, Phosphatidylcholine-sterol acyltransferase, Legumain, Low affinity immunoglobulin gamma Fc region receptor II-c, Fructose-bisphosphate aldolase A, Cytochrome c oxidase subunit 8A, mitochondrial, Pyruvate kinase PKM, Endoglin, Target of Nesh-SH3, Cytochrome c oxidase subunit 5A, mitochondrial, EGF-containing fibulin-like extracellular matrix protein 2, Epididymal secretory protein El, Cathepsin S, Annexin A5, Allograft inflammatory factor 1, Decorin, Complement Cls subcomponent, Low affinity immunoglobulin gamma Fc region receptor Il-b, Leucine-rich alpha-2-glycoprotein, Lysosomal alpha-glucosidase, Disintegrin and metalloproteinase domain- containing protein 9, Transthyretin, Malate dehydrogenase, cytoplasmic, Filamin-A, Retinoic acid receptor responder protein 1, T-celi surface glycoprotein CD4, Procollagen-lysine,2-oxoglutarate 5-dioxygenase 1, Fibrinogen gamma chain, Collagen alpha-2(V) chain, Cystatin-B, Lysosomal protective protein, Granulins, Collagen alpha-l(XIV) chain, C-reactive protein, Beta-l,4-galactosyltransferase 1, Prolow-density lipoprotein receptor-related protein 1, Ig heavy chain V-III region 23, Phosphoglycerate kinase 1, Alpha-2-antiplasmin, V-set and immunoglobulin domain-containing protein 4, Probable serine carboxypeptidase CPVL, NEDD8, Ganglioside GM2 activator, Clusterin, Alpha-2-HS-glycoprotein, HLA class I histocompatibility antigen, B-37 alpha chain, Adenosine deaminase CECR1, HLA class II histocompatibility antigen, DRB1- 11 beta chain, Monocyte differentiation antigen CD14, Erythrocyte band 7 integral membrane protein, Profilin-1, E3 ubiquitin-protein ligase TRIM9, Tripartite motif-containing protein 67, TNF receptor-associated factor 1, Alpha-crystallin A chain, Mitotic checkpoint serine / threonine-protein kinase BUB1, TATA-binding protein-associated factor 2N, Cyclin-F, Centromere protein C, Apoptosis regulator Bcl-2, 2-oxoisovalerate dehydrogenase subunit beta, mitochondrial, Coilin, Nucleoplasmin-3, Homeobox protein Hox-Al, Serine / threonine-protein kinase Chkl, Mitotic checkpoint protein BUB3, Deoxyribonuclease-1, rRNA 2'-0-methyltransferase fibrillarin, Histone HI.3, DNA-directed RNA polymerase III subunit RPC1, DNA-directed RNA polymerase III subunit RPC2, Centromere-associated protein E, inesin-like protein KIF11, Histone H4-like protein type G, Tyrosine 3-monooxygenase, ABC transporter, permease / ATP-binding protein, Translation initiation factor IF-1, Protein FAN, Reticulon-4 receptor, Myeloid cell nuclear differentiation antigen, Glucose-6-phosphate isomerase, High affinity immunoglobulin gamma Fc receptor I, Tryptophan 5-hydroxylase 1, Tryptophan 5-hydroxylase 2, Secretory phospholipase A2 receptor, Aquaporin TIP4-1, Histone H2B type F-S, Histone H2AX, Histone H2A type 1-C, ATP- sensitive inward rectifier potassium channel 10, pVII, hypothetical protein TTV27_gp4, hypothetical protein TTV25_gp2, Alpha-ID adrenergic receptor, Alpha-IB adrenergic receptor, Packaging protein 3, hypothetical protein TTV14_gp2, KRR1 small subunit processome component homolog, Bestrophin-4, Alpha-2C adrenergic receptor, Uncharacterized ORF3 protein, Retinoic acid receptor beta, Retinoic acid receptor alpha, B-cell lymphoma 3 protein, Carbohydrate sulfotransferase 8, Harmonin, Prolactin-releasing peptide receptor, Sphingosine 1-phosphate receptor 1, Acyl-CoA-binding domain- containing protein 5, ORFl, hypothetical protein TTMV3_gp2, Mitochondrial import inner membrane translocase subunit Timl7-B, hypothetical protein TTV2_gp2, Absent in melanoma 1 protein, hypothetical protein TTV28_gpl, hypothetical protein TTV26_gp2, hypothetical protein TTV4_gp2, hypothetical protein TTV28_gp4, Mesencephalic astrocyte-derived neurotrophic factor, hypothetical protein TTMV7_gp2, hypothetical protein TTV19_gp2, pORFl, Pre-histone-like nucleoprotein, hypothetical protein TTV8_gp4, hypothetical protein TTV16_gp2, hypothetical protein TTV15_gp2, ORF2 / 4 protein, P2X purinoceptor 2, membrane glycoprotein E3 CRl-beta, D(2) dopamine receptor, Toll-like receptor 9, Phosphatidylcholine transfer protein, Transcription factor HIVEP2, Probable peptidylarginine deiminase, 60S ribosomal protein L9, Integrin beta-4, Keratin, type II cytoskeletal 1, Chromogranin-A, Histone H3.lt, Voltage-dependent L-type calcium channel subunit alpha-ID, Heat shock 70 kDa protein 1-like, ABC transporter related, UDP-N-acetylglucosamine pyrophosphorylase, Protein GREB1, Aldo / keto reductase, Component of the TOM (Translocase of outer membrane) complex, Excinuclease ABC C subunit domain protein, Phosphoenolpyruvate carboxylase, Arylacetamide deacetylase-like 4, Dynein heavy chain 10, axonemal, Putative Uracil-DNA glycosylase, Spore germination protein PE, Teneurin-1, Putative dehydrogenase, Polysaccharide biosynthesis protein, VCBS, Glutamate / aspartate transport system permease protein GltK, Noggin, Sclerostin, HLA class I histocompatibility antigen, A-30 alpha chain, HLA class I histocompatibility antigen, A-69 alpha chain, HLA class I histocompatibility antigen, B-15 alpha chain, Glutamate receptor ionotropic, NMDA 1, NarH, 40S ribosomal protein S21, Ceruloplasmin, 3-hydroxy-3-methylglutaryl-coenzyme A reductase, 60S ribosomal protein L30, HLA class II histocompatibility antigen gamma chain, HLA class I histocompatibility antigen, Cw-6 alpha chain, HLA class I histocompatibility antigen, Cw-16 alpha chain, Lysosomal alpha-mannosidase, Heat shock protein HSP 90-alpha, Histone H3.2, Histone H2AJ, Voltage-dependent T-type calcium channel subunit alpha-lG, Syncytin-1, Cathelicidin antimicrobial peptide, Tubulin beta-3 chain, Stress-70 protein, mitochondrial, Probable 1,4-alpha-glucan branching enzyme Rv3031, Nuclease-sensitive element-binding protein 1, Complement factor H-related protein 1, Glutaredoxin-1, Gamma-enolase, Platelet-derived growth factor receptor alpha, Collagen alpha-l(VIII) chain, Matrix metalloproteinase-25, Interferon regulatory factor 5, Cytochrome c oxidase subunit 7C, mitochondrial, Heat shock-related 70 kDa protein 2, Cysteine-rich protein 1, NADH dehydrogenase [ubiquinone] flavoprotein 2, mitochondrial, Glutathione S-transferase P, HLA class I histocompatibility antigen, A-68 alpha chain, HLA class II histocompatibility antigen, DM beta chain, Fructose-bisphosphate aldolase C, Beta-2-microglobulin, Cytochrome c oxidase subunit 5B, mitochondrial, Heat shock 70 kDa protein 13, ATP synthase protein 8, 60S ribosomal protein L13a, TRNA nucleotidyltransferase family enzyme, Ferredoxin-dependent glutamate synthase 2, Alkaline phosphatase, tissue-nonspecific isozyme, SLAM family member 5, Slit homolog 3 protein, Transforming growth factor-beta-induced protein ig-h3, Mannose-binding protein C, Calpain-1 catalytic subunit, Actin, gamma-enteric smooth muscle, Creatine kinase M-type, Protein THEM6, Histone-lysine N-methyltransferase ASH1L, C2 calcium-dependent domain-containing protein 4A, Ras association domain-containing protein 10, Hepatocyte cell adhesion molecule, ADAMTS-like protein 5, HLA class II histocompatibility antigen, DRB1-15 beta chain, Anoctamin-2, Phosphoglycerate mutase 1, Por secretion system protein porV (Pg27, IptO), Beta-enolase, Receptor antigen A, 3-oxoacyl- [acyl-carrier-protein] synthase 2, Putative heat shock protein HSP 90-beta 2, Radixin, Tubulin beta-1 chain, Vacuolar protein sorting-associated protein 26A, Serine / threonine-protein phosphatase 5, Catalase, Transketolase, Protein S100- Al, Alpha-centractin, Tubulin beta-4A chain, Beta-centractin, Probable phosphoglycerate mutase 4, Beta-actin-like protein 2, Tubulin beta-4B chain, Phosphoglycerate mutase 2, Alpha-internexin, Tubulin beta-2A chain, Dihydropyrimidinase- related protein 3, Putative heat shock protein HSP 90-beta-3, Fructose-bisphosphate aldolase B, Protein P, Endoplasmin, ATP synthase subunit O, mitochondrial, Heat shock 70 kDa protein 6, Glyceraldehyde-3-phosphate dehydrogenase, testis- specific, Nascent polypeptide-associated complex subunit alpha-2, Carbonic anhydrase 2, Annexin A6, E3 ubiquitin-protein ligase RNF13, Myeloid-derived growth factor, Tyrosine-protein phosphatase non-receptor type substrate 1, Laminin subunit gamma-1, Trichohyalin, Thrombospondin-2, Sialoadhesin, GTPase IMAP family member 1, C4b-binding protein alpha chain, Voltage-dependent anion-selective channel protein 1, Hemopexin, Complement C5, FYVE, RhoGEF and PH domain- containing protein 2, Haptoglobin, Cytochrome P450 1B1, Titin, Myeloma-overexpressed gene 2 protein, Adipocyte enhancer-binding protein 1, Protein-glutamine gamma-glutamyltransferase 2, Protein Trim21, ADAMTS-like protein 3, N- alpha-acetyltransferase 16, NatA auxiliary subunit, Transforming growth factor beta-1, Elastin, Protein disulfide-isomerase A5, Plastin-2, Leukocyte immunoglobulin-like receptor subfamily B member 1, Histamine H2 receptor, Elongation factor 2, Caveolin-1, Ig gamma-2 chain C region, Immunoglobulin superfamily containing leucine-rich repeat protein, 40S ribosomal protein S9, Prolyl 4-hydroxylase subunit alpha-1, Endoplasmic reticulum-Golgi intermediate compartment protein 1, Tetranectin, Serine protease HTRA1, Heterogeneous nuclear ribonucleoprotein Al, Phosducin-like protein 3, Ig lambda chain V-VI region EB4, Fibronectin type III domain-containing protein 1, Keratin, type II cytoskeletal 2 epidermal, Ferritin heavy chain, Y-box-binding protein 3, Complement C4-B, HLA class I histocompatibility antigen, Cw-15 alpha chain, HLA class I histocompatibility antigen, B-42 alpha chain, Collagen alpha-l(V) chain, HLA class I histocompatibility antigen, B- 73 alpha chain, Integral membrane protein 2B, Lysosome-associated membrane glycoprotein 3, Proteoglycan 4, Ribosomal protein S6 kinase alpha-6, Metalloproteinase inhibitor 2, HLA class II histocompatibility antigen, DRB1-12 beta chain, ATP- sensitive inward rectifier potassium channel 15, Vitamin D-binding protein, Osteopontin, Deoxynucleotidyltransferase terminal-interacting protein 2, Olfactory receptor 5K4, Myosin light chain kinase 2, skeletal / cardiac muscle, Non-POU domain-containing octamer-binding protein, Ubiquilin-2, HLA class I histocompatibility antigen, B-51 alpha chain, Minor histocompatibility antigen H13, Glycophorin-C, Eosinophil cationic protein, SWI / SNF complex subunit SMARCC2, Macrophage mannose receptor 1, tRNA-splicing ligase RtcB homolog, Reticulocalbin-2, Heterogeneous nuclear ribonucleoprotein L, 40S ribosomal protein S30, Collagen alpha-3(VI) chain, Matrix metalloproteinase- 14, Antithrombin- III, 60S ribosomal protein LlOa, Retinol-binding protein 4, Heterogeneous nuclear ribonucleoprotein R, Lithostathine-1- alpha, Ret finger protein-like 2, Zinc-alpha-2-glycoprotein, Carboxypeptidase Q, HLA class I histocompatibility antigen, B- 56 alpha chain, Chondroadherin, Cysteine-rich protein 2, Prosaposin, Complement component C9, Apolipoprotein C-II, Protocadherin-16, Leukocyte immunoglobulin-like receptor subfamily B member 4, Galactokinase, Complement factor H, Uncharacterized protein YEL014C, Glycerophosphocholine phosphodiesterase GPCPD1, Echinoderm microtubule- associated protein-like 6, or an isoform, homolog, fragment, variant or derivative of any of these proteins.

[0341] The term "alloantigen" (also referred to as "allogeneic antigen" or "isoantigen") refers to an antigen existing in alternative (allelic) forms in a species, and can therefore induce alloimmunity (or isoimmunity) in members of the same species, e.g. upon blood transfusion, tissue or organ transplantation, or sometimes pregnancy. Typical allogeneic antigens include histocompatibility antigens and blood group antigens. In the context of the present invention, alloantigens are preferably of human origin. Artificial nucleic acid (RNA) molecules encoding antigenic (poly-)peptides or proteins derived from alloantigens can, for instance, be used to induce immune tolerance towards said alloantigen.

[0342] Exemplary allogeneic antigens in the context of the present invention include, without limitation, allogeneic antigens derived or selected from UDP-glucuronosyltransferase 2B17 precursor, MHC class I antigen HLA-A2, Coagulation factor VIII precursor, coagulation factor VIII, Thrombopoietin precursor (Megakaryocyte colony-stimulating factor) (Myeloproliferative leukemia virus oncogene ligand) (C-mpl ligand) (ML) (Megakaryocyte growth and development factor) (MGDF), Integrin beta-3, histocompatibility (minor) HA-1, SMCY, thymosin beta-4, Y-chromosomal, Histone demethylase UTY, HLA class II histocompatibility antigen, DP(W2) beta chain, lysine-specific demethylase 5D isoform 1, myosin-Ig, Probable ubiquitin carboxyl-terminal hydrolase FAF-Y, Pro-cathepsin H, DRB1, MHC DR beta DRwl3 variant, HLA class II histocompatibility antigen, DRB1-15 beta chain, HLA class II histocompatibility antigen, DRBl-1 beta chain precursor, Minor histocompatibility protein HMSD variant form, HLA-DR3, Chain B, Hla-Drl (Dra, Drbl 0101) Human Class Ii Histocompatibility Protein (Extracellular Domain) Complexed With Endogenous Peptide, MHC classll HLA-DRBl, MHC class

[0343] I HLA-A, human leukocyte antigen B, RAS protein activator like-3, anoctamin-9, ATP-dependent RNA helicase DDX3Y, Protocadherin-11 Y-linked, KIAA0020, platelet glycoprotein Ilia leucine-33 form-specific antibody light chain variable region, dead box, Y isoform, ATP-dependent RNA helicase DDX3X isoform 2, HLA-DRBl protein, truncated integrin beta 3, glycoprotein Ilia, platelet membrane glycoprotein lib, Carbonic anhydrase 1, HLA class I histocompatibility antigen, A-

[0344] II alpha chain precursor, HLA-All antigen All.2, HLA class I histocompatibility antigen, A-68 alpha chain, MHC HLA-B51, MHC class I antigen HLA-A30, HLA class I histocompatibility antigen, A-l alpha chain precursor variant, HLA class I histocompatibility antigen B-57, MHC class I antigen, MHC class II antigen, MHC HLA-DR-beta cell surface glycoprotein, DR7 beta-chain glycoprotein, MHC DR-beta, lymphocyte antigen, collagen type V alpha 1, collagen alpha-2(V) chain preproprotein, spllO nuclear body protein isoform d, integrin, alpha 2b (platelet glycoprotein lib of Ilb / IIIa complex, antigen CD41), isoform CRA_c, 40S ribosomal protein S4, Y isoform 1, uncharacterized protein KIAA1551, factor VIII, UDP- glucuronosyltransferase 2B17, HLA class I histocompatibility antigen, A-2 alpha chain, Thrombopoietin, Minor histocompatibility protein HA-1, Lysine-specific demethylase 5D, HLA class II histocompatibility antigen, DP beta 1 chain, Unconventional myosin-Ig, HLA class II histocompatibility antigen, DRB1-13 beta chain, HLA class II histocompatibility antigen, DRBl-1 beta chain, HLA class II histocompatibility antigen, DRB1-3 chain, HLA class I histocompatibility antigen, B-46 alpha chain, Pumilio homolog 3, ATP-dependent RNA helicase DDX3X, Integrin alpha-lib, HLA class I histocompatibility antigen, A-ll alpha chain, HLA class I histocompatibility antigen, B-51 alpha chain, HLA class I histocompatibility antigen, A-30 alpha chain, HLA class I histocompatibility antigen, A-l alpha chain, HLA class I histocompatibility antigen, B-57 alpha chain, HLA class I histocompatibility antigen, B-40 alpha chain, HLA class II histocompatibility antigen, DRB1-7 beta chain, HLA class II histocompatibility antigen, DRB1-12 beta chain, Collagen alpha- 1(V) chain, Collagen alpha-2(V) chain, SpllO nuclear body protein, or an isoform, homolog, fragment, variant or derivative of any of these proteins. Allergenic (poly-)peptides or proteins

[0345] The at least one coding region of the artificial nucleic acid molecule of the invention may encode at least one "allergenic (poly-)peptide or protein". The term "allergenic (poly-)peptide or protein" or "allergen" refers to (poly-)peptides or proteins capable of inducing an allergic reaction, i.e. a pathological immunological reaction characterized by an altered bodily reactivity (such as hypersensitivity), upon exposure to a subject. Typically, "allergens" are implicated in "atopy", i.e. adverse immunological reactions involving immunoglobulin E (IgE). The term "allergen" thus typically means a substance (here: a (poly-)peptide or protein) that is involved in atopy and induces IgE antibodies. Typical allergens envisaged herein include proteinaceous Crustacea-der'wed allergens, insect-derived allergens, mammalian allergens, mollusk-derived allergens, plant allergens and fungal allergens.

[0346] Exemplary allergens in the context of the present invention include, without limitation, allergens derived or selected from from Allergen Pen n 18, Antigen Name, Ara h 2.01 allergen, Melanoma antigen recognized by T-cells 1, Non-specific lipid- transfer protein precursor (LTP) (Allergen Mai d 3), ovalbumin, Parvalbumin beta, Pollen allergen Lol p VA precursor, Pollen allergen Phi p 5b precursor, pru p 1, Pollen allergen Phi p 5a, Der p 1 allergen precursor, Pollen allergen KBG 60 precursor, major allergen Tur cl - Turbo cornutus, Mite group 2 allergen Lep d 2 precursor, Lep D 2 precursor, Major latex allergen Hev b 5, major allergen Cor a 1.0401, Major pollen allergen Art v 1 precursor, Major pollen allergen Bet v 1-A, Beta- lactoglobulin precursor, Alpha-amylase inhibitor 0.28 precursor (CIII) (WMAI-1), group V allergen Phi p 5.0203 precursor, Polygalacturonase precursor, pollen allergen Phi pi, Der f 2 allergen, Probable non-specific lipid-transfer protein 2 precursor, Venom allergen 5 precursor, Pollen allergen Phi p 1 precursor, group V allergen, Chain A, Crystal Structure Of The Calcium-Binding Pollen Allergen Phi P 7 (Polcalcin) At 1.75 Angstroem, Tri r 2 allergen, Pathogenesis-related protein precursor, Globin CTT-III precursor, Major allergen Alt a 1, 13S globulin seed storage protein 3 precursor (Legumin-like protein 3) (Allergen Fag e 1), Lit v 1 tropomyosin, Rubber elongation factor protein, Ovomucoid precursor, Small rubber particle protein, Mag3, Allergen Ara h 1, clone P41B precursor, 13S globulin seed storage protein 1 precursor (Legumin- like protein 1), Pollen allergen Lol p 1 precursor, Major pollen allergen Jun a 1 precursor, Sugi basic protein precursor, profilin, Globin CTT-IV precursor, alkaline serine protease, Glycinin, Conglutin-7 precursor, 2S protein 1, Globin CTT-VI precursor, Ribonuclease mitogillin precursor, Major pollen allergen Cyn d 1, Melanocyte-stimulating hormone receptor, P34 probable thiol protease precursor, Vicilin-like protein, Major allergen Equ c 1 precursor, major allergen Bet v 1, Major allergen Can f 1 precursor, Bd 30K (34 kDa maturing seed protein), Major pollen allergen, Major pollen allergen Hoi I 1 precursor, Kappa-casein precursor, major allergen Dau c 1 / 1, Stress-induced protein SAM22, Major allergen Api g 1, Glycinin G2 precursor, allergen Arah3 / Arah4, Der f 1 allergen, Peptidase 1 precursor (Mite group 1 allergen Eur m 1) (Allergen Eur m I), Oryzin precursor, alpha SI casein, Major pollen allergen Cha o 1 precursor, Non-specific lipid-transfer protein 1, collagen, type I, alpha 2, Der P 1, Peptidase 1 precursor (Major mite fecal allergen Der p 1) (Allergen Der p I), pollen allergen Bet v 1, Phospholipase A2 precursor, Mite group 2 allergen Der p 2, Allergen Mag, Major urinary protein precursor, Major allergen I polypeptide chain 2 precursor, Pen a 1 allergen, Fag e 1, Serum albumin precursor, Pollen allergen Amb a 3, putative alpha-amylase inhibitor 0.28, Albumin seed storage protein, 2S sulfur-rich seed storage protein precursor (Allergen Ber e 1), seed storage protein SSP2, Pro-hevein precursor, pollen allergen, Der p 2 allergen precursor, 2S seed storage protein 1 precursor, prohevein, 2s albumin, major allergen I, polypeptide chain 1, Major allergen I polypeptide chain 1 precursor, Cry j IB precursor, Mite group 2 allergen Der f 2 precursor, beta-casein precursor, Lep D 2 allergen precursor, Allergen Cry j 2 (Pollen allergen), KIAA1224 protein, Hydrophobic seed protein, Allergen Bos d 2 precursor, Allergen II, Mite group 2 allergen Der p 2 precursor, Mite allergen Bio t 5, Peptidase 1 precursor (Major mite fecal allergen Der f 1) (Allergen Der f I), Par j, Can f I, Pollen allergen Lol p 2-A (Lol p II-A), Paramyosin, Alpha-S2-casein precursor, P34 probable thiol protease, beta-lactoglobulin, major allergen Phi p 5, Chain A, Structure Of Erythrocruorin In Different Ligand States Refined At 1.4 Angstroms Resolution, Globin CTT-VIII, Major allergen Asp f 2 precursor, tropomyosin, core protein [Hepatitis B virus], Omega gliadin storage protein, Alpha / beta-gliadin A-V, group 14 allergen protein, Pollen allergen Amb a 1.1 precursor, Glycinin Gl precursor, Pollen allergen Amb a 2 precursor, Cry j 1 precursor, allergen Ziz m 1, Glycine-rich cell wall structural protein 1.8 precursor, Putative pectate lyase 17 precursor, pectate lyase, Pectate lyase precursor, Probable pectate lyase 18 precursor, major allergen beta-lactoglobulin, Major allergen Mai d 1, Alpha-Sl-casein precursor, 2S seed storage protein 1, plectrovirus spvl-r8a2b orf 14 transmembrane protein, allergen I / a, Allergen Cr-PI, Probable non-specific lipid-transfer protein 1, Cr-PII allergen, melanoma antigen gplOO, Alpha-lactalbumin precursor, Chain A, Anomalous Substructure Of Alpha-Lactalbumin, Pilosulin-1 precursor (Major allergen Myr p 1) (Myr p I), Pollen allergen Lol p 3 (Lol p III), Lipocaiin 1 (tear prealbumin), Major pollen allergen Cup a 1, Melanocyte protein Pmel 17 precursor, major house dust allergen, Non-specific lipid-transfer protein 1 (LTP 1) (Major allergen Pru d 3), Non-specific lipid-transfer protein 1 (LTP 1) (Major allergen Pru ar 3), Pollen allergen Lol p 1, alpha-gliadin, Cr-PII, albumin, Alpha-Sl- casein, major allergen I, Ribonuclease mitogillin, beta-casein, UA3-recognized allergen, 2S sulfur-rich seed storage protein 1, unnamed protein product, Polygalacturonase, Major allergen Pru av 1, Der p 1 allergen, lyase allergen, Major pollen allergen Bet v 1-F / I, Gamma-gliadin precursor, 5-hydroxytryptamine receptor 2C (5-HT-2C) (Serotonin receptor 2C) (5- HT2C) (5-HTR2C) (5HT-1C), omega-5 gliadin, Enolase 1 (2-phosphoglycerate dehydratase) (2-phospho-D-glycerate hydrolase), Probable non-specific lipid-transfer protein, Allergen Sin a 1, Glutenin, low molecular weight subunit precursor, Major Peanut Allergen Ara H 1, mal d 3, Eukaryotic translation initiation factor 3 subunit D, tyrosinase-related protein-2, PC4 and SFRSl-interacting protein, RAD51-like 1 isoform 1, Antimicrobial peptide 2, Proteasome subunit alpha type-3, Neurofilament heavy polypeptide (NF-H) (Neurofilament triplet H protein) (200 kDa neurofilament protein), Superoxide dismutase, Major pollen allergen Cor a 1 isoforms 5, 6, 11 and 16, cherry-allergen PRUA1, Allergen Asp f 4 precursor, Chain A, Tertiary Structure Of The Major House Dust Mite Allergen Der P 2, Nmr, 10 Structures, RNA-binding protein NOB1, Dermatan-sulfate epimerase precursor, Squamous cell carcinoma antigen recognized by T-cells 3, Peptidyl-prolyl cis-trans isomerase B precursor, Probable glycosidase crfl, Chain A, Birch Pollen Profilin, Profilin-1, avenin precursor (clone pAvl22) - oat, gamma 3 avenin, coeliac immunoreactive protein 2, CIP-2, prolamin 2 {N-terminal}, avenin gamma-3 - small naked oat (fragment), major pollen allergen Ole e 1, Cytochrome P450 3A1, Ole e 1 protein, Ole e 1.0102 protein, Der f 2, GroEL- like chaperonin, major allergen Arahl, manganese superoxide dismutase, beta-l,3-glucanase-like protein, Ara h 1 allergen, Major allergen Alt a 1 precursor, Bla g 4 allergen, Per a 4 allergen variant 1, Lyc e 2.0101, pectate lyase 2, allergen, hypothetical protein, Probable pectate lyase P59, Pollen allergen Amb a 1.4, Patatin-2-Kuras 1, calcium-binding protein, vicilin seed storage protein, major allergenic protein Mal f4, pel protein, ripening-related pectate lyase, pectate lyase / Amb allergen, Bet v 4, Polcalcin Bet v 4, Mite allergen Der f 6, Allergen Alt a 2, Extracellular elastinolytic metalloproteinase, pectate lyase-like protein, Pectate lyase E, Profilin-2, Venom allergen 5, Cucumisin, Putative peroxiredoxin, putative pectate lyase precursor, Serum albumin, pollen allergen Phi p 11, serine (or cysteine) proteinase inhibitor, clade B (ovalbumin), member 3, Allergen Bla g 4 precursor (Bla g IV), Allergen Pen n 13, Hyaluronidase A, pectate lyase homolog, putative allergen Cup a 1, Major pollen allergen 3un v 1, putative allergen jun o 1, Pollen allergen Amb a 1.2, Probable pectate lyase 13, P8 protein, Cytochrome c, Glucan endo-l,3-beta-glucosidase, basic vacuolar isoform, 13S globulin, beta-1,3- glucanase, beta-1, 3-glucananse, Glutenin, high molecular weight subunit DX5 precursor, X-type HMW glutenin, Glutenin, high molecular weight subunit DX5, high-molecular-weight glutenin subunit 1DX2.1, high molecular weight glutenin subunit, US globulin-like protein, seed storage protein, alpha-L-Fucp-(l->3)-[alpha-D-Manp-(l->6)-[beta-D-Xylp-(l- >2)]-beta-D-Manp-(l->4)-beta-D-GlcpNAc-(l->4)]-D-GlcpNAc, beta casein B, type 1 non-specific lipid transfer protein precursor, Fas AMA, Caspase-8 precursor, H antigen glycoprotein, H antigen gl, Heat shock protein HSP 90-beta, dihydrolipoamide S-acetyltransferase (E2 component of pyruvate dehydrogenase complex), isoform CRA_a, Group V allergen Phi p 5.0103 precursor, Phi p6 allergen precursor, Group V allergen Phi p 5, Major pollen allergen Phi p 4 precursor, Pollen allergen Phi p V, Phi p 3 allergen, Pollen allergen Phi pi precursor, Chain A, Crystal Structure Of Phi P 1, A Major Timothy Grass Pollen Allergen, Pollen allergen Phi p 4, Profilin-3, Profilin-2 / 4, Pollen allergen Phi p 2, Phi p6 IgE binding fragment, Phlp5, Chain N, Crystal Structure Of Phi P 6, A Major Timothy Grass Pollen Allergen Co-Crystallized With Zinc, group V allergen Phi p 5.0206 precursor, allergenic protein, Major allergen Ani s 1, allergen Ana o 2, ENSP-like protein, BW 16kDa allergen, alpha2(I) collagen, collagen a2(I), type 1 collagen alpha 2, Cyn d 1, Major pollen allergen Aln g 1 (Allergen Aln g I), allergen Len c 1.0101, galactomannan, Aspartic protease Bla g 2, alcohol dehydrogenase, lipid transfer protein precursor, alpha / beta gliadin precursor, Der f 7 allergen, Der p 7 allergen polypeptide, non-specific lipid transfer protein, Major allergen I polypeptide chain 1, prunin 1 precursor, prunin 2 precursor, IIS legumin protein, Ara h 7 allergen precursor, vicilin-like protein precursor, allergen Arah6, parvalbumin like 2, paralbumin like 1, casein kappa, Ribosomal biogenesis protein LAS1L, Pen c 1, SchS21 protein, Inactive hyaluronidase B, Mupl protein, Macrophage migration inhibitory factor, Eukaryotic translation initiation factor 2 subunit 3, CR2 / CD21 / C3d / Epstein-Barr virus receptor precursor, DNA topoisomerase 2-alpha, pollen allergen Cyn d 23, major allergen Bla g 1.02, pectin methylesterase allergenic protein, major allergen Pha a 5 isoform, 2S albumin seed storage protein, aldehyde dehydrogenase (NAD+), pollen allergen Poa p 5, Bla g 1.02 variant allergen, partial, Major pollen allergen Lol p 5b, allergen Bla g 6.0301, protein disulfide isomerase, putative mannitol dehydrogenase, pollen allergen Lol p 4, Aspartic protease pepl, enolase, IgE-binding protein, Minor allergen Alt a 5, HDM allergen, Chain A, Crystal Structure Of An Mbp-Der P 7 Fusion Protein, allergen Bla g 6.0201, major allergen Bla g 1.0101, alpha-amylase, minor allergen, ribosomal protein P2, metalloprotease (MEP), autophagic serine protease Alp2, allergenic isoflavone reductase-like protein Bet v 6.0102, Chain A, Crystal Structure Of The Complex Of Antibody And The Allergen Bla G 2, minor allergen, thioredoxin TrxA, enolase, allergen Cla h 6, glutathione-S-transferase, molecular chaperone and allergen Mod-E / Hsp90 / Hspl, major allergen Asp F2, Mite allergen Der p 3, Chain B, Crystal Structure Of Aspergillus Fumigatus Mnsod, Glutathione S-transferase (GST class-sigma) (Major allergen Bla g 5), Minor allergen Cla h 7, unknown protein, allergenic cerato-platanin Asp F13, art v 2 allergen, Polcalcin Aln g 4, major allergen and cytotoxin AspFl, pollen allergen Que a 1 isoform, trypsin-like serine protease, Mite group 6 allergen Der p 6, allergen Asp F7, cell wall protein PhiA, 60 kDa allergen Der f 18p, hsp70, Sal k 3 pollen allergen, acidic ribosomal protein P2, Chain B, Crystal Structure Of The Nadp-Dependent Mannitol Dehydrogenase From Cladosporium Herbarum., Art v 3.0301 allergen precursor, 60S ribosomal protein L3, Der p 20 allergen, Pollen allergen Sal k 1, Per a 6 allergen, gelsolin-like allergen Der f 16, Chain A, Structural Characterization Of The Tetrameric Form Of The Major Cat Allergen Fel D 1, Glutathione S-transferase, Fel d 4 allergen, Major pollen allergen Dac g 4, Group I allergen Ant o I (Form 1), pollen, allergen Bla g 6.0101, cystatin, Mite allergen Der p 5, allergen Fra e 1, allergen Asp F4, major antigen-like protein, PR5 allergen Cup s 3.1 precursor, heat shock...

Claims

CLAIMS1. An artificial nucleic acid molecule comprising a. at least one 5' untranslated region (5' UTR) element derived from a 5' UTR of a gene selected from the group consisting of HSD17B4, ASAH1, ATP5A1, MP68, NDUFA4, NOSIP, RPL31, SLC7A3, TUBB4B and UBQLN2; b. at least one 3' untranslated region (3' UTR) element derived from a 3' UTR of a gene selected from the group consisting of PSMB3, CASP1, COX6B1, GNAS, NDUFA1 and RPS9; and optionally c. at least one coding region operably linked to said 5' UTR and said 3' UTR.

2. The artificial nucleic acid molecule according to claim 1, wherein said 5' UTR and / or said 3' UTR is heterologous to said coding region.

3. The artificial nucleic acid molecule according to any one of claims 1 or 2, wherein each of said UTRs comprises the naturally occurring DNA sequence, and homologs, variants, fragments, and corresponding RNA sequences thereof.

4. The artificial nucleic acid molecule according to any one of claims 1 to 3, comprising a-1. at least one 5' UTR element derived from a 5'UTR of a HSD17B4 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR element derived from a 3'UTR of a PSMB3 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or a-2. at least one 5' UTR element derived from a 5'UTR of a NDUFA4 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR element derived from a 3'UTR of a PSMB3 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or a-3. at least one 5' UTR element derived from a 5'UTR of a SLC7A3 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR element derived from a 3'UTR of a PSMB3 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or a-4. at least one 5' UTR element derived from a 5'UTR of a NOSIP gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR element derived from a 3'UTR of a PSMB3 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or a-5. at least one 5' UTR element derived from a 5'UTR of a MP68 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR element derived from a 3'UTR of a PSMB3 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or b-1. at least one 5' UTR element derived from a 5'UTR of a UBQLN2 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR element derived from a 3'UTR of a RPS9 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; orb-2. at least one 5' UTR element derived from a 5'UTR of a ASAHl gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR element derived from a 3'UTR of a RPS9 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or b-3. at least one 5' UTR element derived from a 5'UTR of a HSD17B4 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR element derived from a 3'UTR of a RPS9 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or b-4. at least one 5' UTR element derived from a 5'UTR of a HSD17B4 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR element derived from a 3'UTR of a CASP1 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or b-5. at least one 5' UTR element derived from a 5'UTR of a NOSIP gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR element derived from a 3'UTR of a COX6B1 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or c-1. at least one 5' UTR element derived from a 5'UTR of a NDUFA4 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR element derived from a 3'UTR of a RPS9 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or c-2. at least one 5' UTR element derived from a 5'UTR of a NOSIP gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR element derived from a 3'UTR of a NDUFA1 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or c-3. at least one 5' UTR element derived from a 5'UTR of a NDUFA4 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR element derived from a 3'UTR of a COX6B1 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or c-4. at least one 5' UTR element derived from a 5'UTR of a NDUFA4 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR element derived from a 3'UTR of a NDUFA1 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or c-5. at least one 5' UTR element derived from a 5'UTR of a ATP5A1 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR element derived from a 3'UTR of a PSMB3 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or d-1. at least one 5' UTR element derived from a 5'UTR of a RPL31 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR element derived from a 3'UTR of a PSMB3 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or d-2. at least one 5' UTR element derived from a 5'UTR of a ATP5A1 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR element derived from a 3'UTR of a CASP1 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; ord-3. at least one 5' UTR element derived from a 5'UTR of a SLC7A3 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR element derived from a 3'UTR of a GNAS1 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or d-4. at least one 5' UTR element derived from a 5'UTR of a HSD17B4 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR element derived from a 3'UTR of a NDUFA1 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or d-5. at least one 5' UTR element derived from a 5'UTR of a SLC7A3 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR element derived from a 3'UTR of a NDUFA1 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or e-1. at least one 5' UTR element derived from a 5'UTR of a TUBB4B gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR element derived from a 3'UTR of a RPS9 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or e-2. at least one 5' UTR element derived from a 5'UTR of a RPL31 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR element derived from a 3'UTR of a RPS9 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or e-3. at least one 5' UTR element derived from a 5'UTR of a MP68 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR element derived from a 3'UTR of a RPS9 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or e-4. at least one 5' UTR element derived from a 5'UTR of a NOSIP gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR element derived from a 3'UTR of a RPS9 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or e-5. at least one 5' UTR element derived from a 5'UTR of a ATP5A1 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR element derived from a 3'UTR of a RPS9 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or e-6. at least one 5' UTR element derived from a 5'UTR of a ATP5A1 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR element derived from a 3'UTR of a COX6B1 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or f-1. at least one 5' UTR element derived from a 5'UTR of a ATP5A1 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR element derived from a 3'UTR of a GNAS gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or f-2. at least one 5' UTR element derived from a 5'UTR of a ATP5A1 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR element derived from a 3'UTR of a NDUFA1 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; orf.3 at least one 5' UTR element derived from a 5'UTR of a HSD17B4 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR element derived from a 3'UTR of a COX6B1 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or f-4 at least one 5' UTR element derived from a 5'UTR of a HSD17B4 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR element derived from a 3'UTR of a GNAS1 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or f-5. at least one 5' UTR element derived from a 5'UTR of a MP68 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR element derived from a 3'UTR of a COX6B1 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or g-1. at least one 5' UTR element derived from a 5'UTR of a MP68 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR element derived from a 3'UTR of a NDUFA1 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or g-2. at least one 5' UTR element derived from a 5'UTR of a NDUFA4 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR element derived from a 3'UTR of a CASP1 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or g-3. at least one 5' UTR element derived from a 5'UTR of a NDUFA4 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR element derived from a 3'UTR of a GNAS gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or g-4 at least one 5' UTR element derived from a 5'UTR of a NOSIP gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR element derived from a 3'UTR of a CASP1 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or g-5 at least one 5' UTR element derived from a 5'UTR of a RPL31 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR element derived from a 3'UTR of a CASP1 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or h-1 at least one 5' UTR element derived from a 5'UTR of a RPL31 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR element derived from a 3'UTR of a COX6B1 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or h-2 at least one 5' UTR element derived from a 5'UTR of a RPL31 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR element derived from a 3'UTR of a GNAS gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or h-3 at least one 5' UTR element derived from a 5'UTR of a RPL31 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR element derived from a 3'UTR of a NDUFA1 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; orh-4 at least one 5' UTR element derived from a 5'UTR of a SLC7A3 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR element derived from a 3'UTR of a CASP1 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or h-5 at least one 5' UTR element derived from a 5'UTR of a SLC7A3 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR element derived from a 3'UTR of a COX6B1 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or i-1 at least one 5' UTR element derived from a 5'UTR of a SLC7A3 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR element derived from a 3'UTR of a RPS9 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or i-2 at least one 5' UTR element derived from a 5'UTR of a Ndufa4.1 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR element derived from a 3'UTR of a CASP1 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof.The artificial nucleic acid molecule according to claim 4, comprising UTR elements according to a-1, a-2, a-3, a- 4 or a-5, preferably according to a-1.The artificial nucleic acid molecule according to claim 4, comprising UTR elements according to a-2 (NDUFA4 / PSMB3); a-5 (MP68 / PSMB3); c-1 (NDUFA4 / RPS9); a-1 (HSD17B4 / PSMB3); e-3 (MP68 / RPS9); e-4 ( NOSIP / RPS9); a-4 ( NOSIP / PSMB3); e-2 (RPL31 / RPS9); e-5 (ATP5A1 / RPS9); d-4 (HSD17B4 / NUDFAl); b-5 ( NOSIP / COX6B1); a-3 (SLC7A3 / PSMB3); b-1 (UBQLN2 / RPS9); b-2 (ASAH1 / RPS9); b-4 (HSD17B4 / CASP1); e-6 (ATP5A1 / COX6B1); b-3 (HSD17B4 / RPS9); g-5 (RPL31 / CASP1); h-1 (RPL31 / COX6B1); and / or c-5 (ATP5A1 / PSMB3).The artificial nucleic acid molecule according to claim 4, comprising UTR elements according to a-1 (HSD17B4 / PS B3); a-3 (SLC7A3 / PSMB3); e-2 (RPL31 / RPS9); a-5 (MP68 / PSMB3); d-1 (RPL31 / PSMB3); a-2 (NDUFA4 / PS B3); h-1 (RPL31 / COX6B1); b-1 (UBQLN2 / RPS9); a-4 (NOSIP / PSMB3); c-5 (ATP5A1 / PSMB3); b-5 (NOSIP / COX6B1); d-4 (HSD17B4 / NDUFA1); i-1 (SLC7A3 / RPS9); i-2 (Ndufa4.1 / CASP1); f-3 (HSD17B4 / COX6B1); b-4 (HSD17B4 / CASP1); g-5 (RPL31 / CASP1); c-2 (NOSIP / NDUFA1); e-4 (NOSIP / RPS9); c-4 (NDUFA4 / NDUFA1); and / or d-5 (SLC7A3 / NDUFA1).The artificial nucleic acid molecule according to claim 4, comprising UTR elements according to a-4 (NOSIP / PSMB3); a-1 (HSD17B4 / PSMB3); a-5 (MP68 / PSMB3); d-3 (SLC7A3 / GNAS); a-2 (NDUFA4 / PSMB3); a-3 (SLC7A3 / PSMB3); d-5 (SLC7A3 / NDUFA1); i-1 (SLC7A3 / RPS9); d-1 (RPL31 / PS B3); d-4 (HSD17B4 / NDUFA1); b-3 (HSD17B4 / RPS9); f-3 (HSD17B4 / COX6B1); f-4 (HSD17B4 / GNAS); h-5 (SLC7A3 / COX6B1); g- 4 (NOSIP / CASP1); c-3 (NDUFA4 / COX6B1); b-1 (UBQLN2 / RPS9); c-5 (ATP5A1 / PSMB3); h-4 (SLC7A3 / CASP1); h-2 (RPL31 / GNAS); e-1 (TUBB4B / RPS9); f-2 (ATP5A1 / NDUFA1); c-2 (NOSIP / NDUFA1); b-5 (NOSIP / COX6B1); and / or e-4 (NOSIP / RPS9.1)The artificial nucleic acid molecule according to any one of claims 1 to 8, wherein said 5'UTR element derived from a HSD17B4 gene comprises or consists of a DNA sequence according to SEQ ID NO: 1 or a DNA sequence having, in increasing order of preference, at least 50%, 60%, 70%,80%, 90%, 95%, 96%, 97%, 98%, or 99% sequence identity to the nucleic acid sequence according to SEQ ID NO: 1, or a fragment or a variant thereof; or an RNA sequence according to SEQ ID NO: 2, or an RNA sequence having, in increasing order of preference, at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% sequence identity to the nucleic acid sequence according to SEQ ID NO: 2, or a fragment or a variant thereof; said 5'UTR element derived from a ASAH1 gene comprises or consists of a DNA sequence according to SEQ ID NO: 3 or a DNA sequence having, in increasing order of preference, at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% sequence identity to the nucleic acid sequence according to SEQ ID NO: 3, or a fragment or variant thereof; or an RNA sequence according to SEQ ID NO: 4, or an RNA sequence having, in increasing order of preference, at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% sequence identity to the nucleic acid sequence according to SEQ ID NO: 4, or a fragment or a variant thereof; said 5'UTR element derived from a ATP5A1 gene comprises or consists of a DNA sequence according to SEQ ID NO: 5, or a DNA sequence having, in increasing order of preference, at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% sequence identity to the nucleic acid sequence according to SEQ ID NO: 5, or a fragment or variant thereof; or an RNA sequence according to SEQ ID NO: 6, or an RNA sequence having, in increasing order of preference, at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% sequence identity to the nucleic acid sequence according to SEQ ID NO: 6, or a fragment or a variant thereof; said 5'UTR element derived from a MP68 gene comprises or consists of a DNA sequence according to SEQ ID NO: 7, or a DNA sequence having, in increasing order of preference, at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% sequence identity to the nucleic acid sequence according to SEQ ID NO: 7, or a fragment or variant thereof; or an RNA sequence according to SEQ ID NO: 8, or an RNA sequence having, in increasing order of preference, at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% sequence identity to the nucleic acid sequence according to SEQ ID NO: 8, or a fragment or a variant thereof; said 5'UTR element derived from a NDUFA4 gene comprises or consists of a DNA sequence according to SEQ ID NO: 9, or a DNA sequence having, in increasing order of preference, at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% sequence identity to the nucleic acid sequence according to SEQ ID NO: 9, or a fragment or variant thereof; or an RNA sequence according to SEQ ID NO: 10, or an RNA sequence having, in increasing order of preference, at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% sequence identity to the nucleic acid sequence according to SEQ ID NO: 10, or a fragment or a variant thereof; said 5'UTR element derived from a NOSIP gene comprises or consists of a DNA sequence according to SEQ ID NO: 11, or a DNA sequence having, in increasing order of preference, at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% sequence identity to the nucleic acid sequence according to SEQ ID NO: 11, or a fragment or variant thereof; or an RNA sequence according to SEQ ID NO: 12, or an RNA sequence having, in increasing order of preference, at least 50%, 60%, 70%, 80%, 90%, 95%,96%, 97%, 98%, or 99% sequence identity to the nucleic acid sequence according to SEQ ID NO: 12, or a fragment or a variant thereof; said 5'UTR element derived from a RPL31 gene comprises or consists of a DNA sequence according to SEQ ID NO: 13, or a DNA sequence having, in increasing order of preference, at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% sequence identity to the nucleic acid sequence according to SEQ ID NO: 13, or a fragment or variant thereof; an RNA sequence according to SEQ ID NO: 14, or an RNA sequence having, in increasing order of preference, at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% sequence identity to the nucleic acid sequence according to SEQ ID NO: 14, or a fragment or a variant thereof; said 5'UTR element derived from a SLC7A3 gene comprises or consists of a DNA sequence according to SEQ ID NO: 15, or a DNA sequence having, in increasing order of preference, at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% sequence identity to the nucleic acid sequence according to SEQ ID NO: 15, or a fragment or variant thereof; or an RNA sequence according to SEQ ID NO: 16, or an RNA sequence having, in increasing order of preference, at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% sequence identity to the nucleic acid sequence according to SEQ ID NO: 16, or a fragment or a variant thereof; said 5'UTR element derived from a TUBB4B gene comprises or consists of a DNA sequence according to SEQ ID NO: 17, or a DNA sequence having, in increasing order of preference, at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% sequence identity to the nucleic acid sequence according to SEQ ID NO: 17, or a fragment or variant thereof; or an RNA sequence according to SEQ ID NO: 18, or an RNA sequence having, in increasing order of preference, at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% sequence identity to the nucleic acid sequence according to SEQ ID NO: 18, or a fragment or a variant thereof; said 5'UTR element derived from a UBQLN2 gene comprises or consists of a DNA sequence according to SEQ ID NO: 19, or a DNA sequence having, in increasing order of preference, at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% sequence identity to the nucleic acid sequence according to SEQ ID NO: 19, or a fragment or variant thereof; or an RNA sequence according to SEQ ID NO: 20, or an RNA sequence having, in increasing order of preference, at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% sequence identity to the nucleic acid sequence according to SEQ ID NO: 20, or a fragment or a variant thereof; said 3'UTR element derived from a PSMB3 gene comprises or consists of a DNA sequence according to SEQ ID NO: 23, or a DNA sequence having, in increasing order of preference, at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% sequence identity to the nucleic acid sequence according to SEQ ID NO: 23, or a fragment or variant thereof; or an RNA sequence according to SEQ ID NO: 24, or an RNA sequence having, in increasing order of preference, at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% sequence identity to the nucleic acid sequence according to SEQ ID NO: 24, or a fragment or a variant thereof;said 3'UTR element derived from a CASP1 gene comprises or consists of a DNA sequence according to SEQ ID NO; 25, or a DNA sequence having, in increasing order of preference, at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% sequence identity to the nucleic acid sequence according to SEQ ID NO: 25, or a fragment or variant thereof; or an RNA sequence according to SEQ ID NO: 26, or an RNA sequence having, in increasing order of preference, at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% sequence identity to the nucleic acid sequence according to SEQ ID NO: 26, or a fragment or a variant thereof; said 3'UTR element derived from a COX6B1 gene comprises or consists of a DNA sequence according to SEQ ID NO: 27, or a DNA sequence having, in increasing order of preference, at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% sequence identity to the nucleic acid sequence according to SEQ ID NO: 27, or a fragment or variant thereof; or an RNA sequence according to SEQ ID NO: 28, or an RNA sequence having, in increasing order of preference, at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% sequence identity to the nucleic acid sequence according to SEQ ID NO: 28, or a fragment or a variant thereof; said 3'UTR element derived from a GNAS gene comprises or consists of a DNA sequence according to SEQ ID NO: 29, or a DNA sequence having, in increasing order of preference, at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% sequence identity to the nucleic acid sequence according to SEQ ID NO: 29, or a fragment or variant thereof; or an RNA sequence according to SEQ ID NO: 30, or an RNA sequence having, in increasing order of preference, at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% sequence identity to the nucleic acid sequence according to SEQ ID NO: 30, or a fragment or a variant thereof; said 3'UTR element derived from a NDUFA1 gene comprises or consists of a DNA sequence according to SEQ ID NO: 31, or a DNA sequence having, in increasing order of preference, at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% sequence identity to the nucleic acid sequence according to SEQ ID NO: 31, or a fragment or variant thereof; or an RNA sequence according to SEQ ID NO: 32, or an RNA sequence having, in increasing order of preference, at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% sequence identity to the nucleic acid sequence according to SEQ ID NO: 32, or a fragment or a variant thereof; and / or said 3'UTR element derived from a RPS9 gene comprises or consists of a DNA sequence according to SEQ ID NO: 33, or a DNA sequence having, in increasing order of preference, at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% sequence identity to the nucleic acid sequence according to SEQ ID NO: 33, or a fragment or variant thereof; or an RNA sequence according to SEQ ID NO: 34, or an RNA sequence having, in increasing order of preference, at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% sequence identity to the nucleic acid sequence according to SEQ ID NO: 34, or a fragment or a variant thereof.The artificial nucleic acid molecule according to any one of claims 1 to 9, wherein said coding region is located between said 5' UTR and said 3' UTR, preferably downstream of said 5' UTR and upstream of said 3'UTR.

11. The artificial nucleic acid molecule according to any one of claims 1 to 10, wherein the at least one coding region encodes at least one (poly-)peptide or protein of interest optionally selected from an antigenic (poly-)peptide or protein, allergenic (poly-)peptide or protein, a therapeutic (poly-)peptide or protein, an antibody, or a fragment, variant or derivative of said (poly-)peptide or protein of interest.

12. The artificial nucleic acid molecule according to claim 11, wherein said at least one antigenic (poly-)peptide or protein is selected from a tumor antigen, a pathogenic antigen, an autoantigen, an alloantigen, or an allergenic antigen.

13. The artificial nucleic acid molecule according to claim 12, wherein said at least one pathogenic antigen is selected from a bacterial, viral, fungal or protozoal antigen.The artificial nucleic acid molecule according to claim 11, wherein said therapeutic (poly-)peptide or protein selected from a therapeutic (poly-)peptide or protein replacing an absent, deficient or mutated protein; a therapeutic (poly-)peptide or protein beneficial for treating inherited or acquired diseases, infectious diseases, or neoplasms (f.e. cancer or tumor diseases); an adjuvant or immuno-stimulating therapeutic (poly-)peptide or protein;- a therapeutic antibody;- a peptide hormone;- a gene editing agent; an immune checkpoint inhibitor;- a T cell receptor; an enzyme; and / or- a variant, fragment or derivative of any of said therapeutic (poly-)peptides or proteins.The artificial nucleic acid molecule according to any one of claims 10 to 14, wherein said at least one coding region further encodes(a) at least one effector domain;(b) at least one peptide or protein tag;(c) at least one localization signal or sequence;(d) at least one nuclear localization signal (NLS);(e) at least one signal peptide; and / or(f) at least one peptide linker;(g) a secretory signal peptide (SSP),(h) a multimerization element including dimerization, trimerization, tetramerization or oligomerization elements;(i) a virus like particle (VLP) forming element; (j) a transmembrane element;(k) a dendritic cell targeting element; (I) an immunological adjuvant element; (m) an element promoting antigen presentation; (n) a 2A peptide;(o) an element that extends protein half-life; and / or(p) an element for post-translational modification (e.g. glycosylation), wherein the artificial nucleic acid molecule further optionally comprises at least one internal ribosomal entry site (IRES) and / or at least one miRNA binding sites.

16. The artificial nucleic acid molecule according to any one of claims 1 to 15, wherein said at least one coding region encodes a (poly-)peptide or protein comprising or consisting of an amino acid sequence according to any one of SEQ ID NOs: 41-45, or an amino acid sequence having, in increasing order of preference, at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence according to any one of SEQ ID NOs: 42-45, or a variant or fragment of any of these sequences.

17. The artificial nucleic acid molecule according to any one of claims 1 to 15, wherein the at least one coding region of said artificial nucleic acid molecule comprises or consists of a nucleic acid sequence according to any one of SEQ ID NOs: 46-49; or a nucleic acid sequence having, in increasing order of preference, at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% sequence identity to the any one of said nucleic acid sequences.

18. The artificial nucleic acid molecule according to any one of claims 1 to 16, wherein said artificial nucleic acid molecule comprises or consists of a nucleic acid sequence according to any one of SEQ ID NOs: 50-368, or a nucleic acid sequence having, in increasing order of preference, at least 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% sequence identity to the any one of said nucleic acid sequences.

19. The artificial nucleic acid molecule according to any one of claims 1 to 17, wherein said artificial nucleic acid molecule is an RNA.

20. The RNA according to claim 19, wherein the RNA is mono-, bi-, or multicistronic.

21. The RNA according to claim 19 or 20, wherein the RNA is an mRNA, a viral RNA, self-replicating RNAor a replicon RNA.

22. The artificial nucleic acid, preferably RNA, according to any one of claims 1 to 21, wherein said artificial nucleic acid is a modified nucleic acid, preferably a stabilized nucleic acid, or wherein the artificial nucleic acid comprises at least one modified or non-naturally occurring nucleotide, backbone modification, sugar modification or base modification.

23. The artificial nucleic acid, preferably RNA, according to any one of claims 1 to 22, wherein the G / C content of the at least one coding region of the artificial nucleic acid is increased compared to the G / C content of the corresponding coding sequence of the corresponding wild-type artificial nucleic acid, and / or wherein the C content of the at least one coding region of the artificial nucleic acid is increased compared to the C content of the corresponding coding sequence of the corresponding wild-type artificial nucleic acid, and / or wherein the codons in the at least one coding region of the artificial nucleic acid are adapted to human codon usage, wherein the codon adaptation index (CAI) is preferably increased or maximised in the at least one coding sequence of the artificial nucleic acid, wherein the amino acid sequence encoded by the artificial nucleic acid is preferably not being modified compared to the amino acid sequence encoded by the corresponding wild-type artificial nucleic acid.

24. The artificial nucleic acid, preferably RNA, according to any one of claims 1 to 23, which comprises a 5'-CAP structure, preferably m7GpppN or Capl.

25. The artificial nucleic acid, preferably RNA, according to any one of 1 to 24, which comprises at least one histone stem-loop.

26. The artificial nucleic acid, preferably RNA, according to claim 25, wherein the at least one histone stem-loop comprises a nucleic acid sequence according to the following formulae (I) or (II): formula (I) (stem-loop sequence without stem bordering elements);[N0-2GN3-5] [No-4(U / T)No-4] [N3-5CN0- steml |00p stem2 formula (II) (stem-loop sequence with stem bordering elements):N1-6 [N0-2GN3-5] [No-4(U / T)No-4] [N3-5CN0-2] N1-6 stem 1 stem 1 loop stem2 stem2bordering borderingelement element wherein: is a consecutive sequence of 1 to 6, preferably of 2 to 6, more preferably of 2 to 5, even more preferably of 3 to 5, most preferably of 4 to 5 or 5 N, wherein each N is independently from another selected from a nucleotide selected from A, U, T, G and C, or a nucleotide analogue thereof; is reverse complementary or partially reverse complementary with element stem2, and is a consecutive sequence between of 5 to 7 nucleotides; wherein N0-2 is a consecutive sequence of 0 to 2, preferably of 0 to 1, more preferably of 1 N, wherein each N is independently from another selected from a nucleotide selected from A, U, T, G and C or a nucleotide analogue thereof; wherein N3-5 is a consecutive sequence of 3 to 5, preferably of 4 to 5, more preferably of 4 N, wherein each N is independently from another selected from a nucleotide selected from A, U, T, G and C or a nucleotide analogue thereof, and wherein G is guanosine or an analogue thereof, and may be optionally replaced by a cytidine or an analogue thereof, provided that its complementary nucleotide cytidine in stem2 is replaced by guanosine; loop sequence [No-4(U / T)No-4] is located between elements steml and stem2, and is a consecutive sequence of 3 to 5 nucleotides, more preferably of 4 nucleotides;wherein each No-4is independent from another a consecutive sequence of 0 to 4, preferably of 1 to 3, more preferably of 1 to 2 N, wherein each N is independently from another selected from a nucleotide selected from A, U, T, G and C or a nucleotide analogue thereof; and wherein U / T represents uridine, or optionally thymidine; stem2 [N3-5CN0-2] is reverse complementary or partially reverse complementary with element steml, and is a consecutive sequence between of 5 to 7 nucleotides; wherein is a consecutive sequence of 3 to 5, preferably of 4 to 5, more preferably of 4 N, wherein each N is independently from another selected from a nucleotide selected from A, U, T, G and C or a nucleotide analogue thereof; wherein N0-2 is a consecutive sequence of 0 to 2, preferably of 0 to 1, more preferably of 1 N, wherein each N is independently from another selected from a nucleotide selected from A, U, T, G and C or a nucleotide analogue thereof; and wherein C is cytidine or an analogue thereof, and may be optionally replaced by a guanosine or an analogue thereof provided that its complementary nucleotide guanosine in steml is replaced by cytidine; whereinsteml and stem2 are capable of base pairing with each otherforming a reverse complementary sequence, wherein base pairing may occur between steml and stem2, or forming a partially reverse complementary sequence, wherein an incomplete base pairing may occur between steml and stem2.The artificial nucleic acid, preferably RNA, according to claim 25 or 26, wherein the at least one histone stem- loop comprises a nucleic acid sequence according to the following formulae (la) or (Ila):formula (la) (stem-loop sequence without stem bordering elements):[N0-1GN3-5] [Ni-3(U / T)No-2] [N3-5CN0-1]v ' Ysteml loop stem2 formula (Ila) (stem-loop sequence with stem bordering elements):N2-5 [N0-1GN3-5] [Ni-3(U / T)No-2] [N3-5CN0-13 N2-5 stem 1 stem 1|oopstem2 stem2 bordering borderingelement element28. The artificial nucleic acid, preferably RNA, according to any one of claims 1 to 27, optionally comprising a poly(A) sequence, preferably comprising 10 to 200, 10 to 100, 40 to 80 or 50 to 70 adenosine nucleotides.

29. The artificial nucleic acid, preferably RNA, according to any one of claims 1 to 28, optionally comprising a poly(C) sequence, preferably comprising 10 to 200, 10 to 100, 20 to 70, 20 to 60 or 10 to 40 cytosine nucleotides.

30. The artificial nucleic acid, preferably RNA, according to any one of claims 1 to 29, which comprises, preferably in 5' to 3' direction, the following elements: a) a 5 -CAP structure, preferably m7GpppN or Capl; b) a 5'-UTR element, which comprises or consists of a nucleic acid sequence, which is derived from a 5'- UTR as defined in any one of claims 1 to 9, preferably comprising an nucleic acid sequence corresponding to the nucleic acid sequence according to SEQ ID NO: 1-20 or a homolog, fragment or variant thereof, c) at least one coding sequence as defined in any one of claims 10 to 18, d) a 3'-UTR element, which comprises or consists of a nucleic acid sequence, which is derived from a 3'- UTR as defined in any one of claims 1 to 9, preferably comprising a nucleic acid sequence corresponding to the nucleic acid sequence according to SEQ ID NO: 23-34, or a homolog, a fragment or a variant thereof, e) optionally a poly(A) tail, preferably consisting of 10 to 1000, 10 to 500, 10 to 300 10 to 200, 10 to 100, 40 to 80 or 50 to 70 adenosine nucleotides, f) optionally a poly(C) tail, preferably consisting of 10 to 200, 10 to 100, 20 to 70, 20 to 60 or 10 to 40 cytosine nucleotides, and g) optionally a histone stem-loop.

31. Composition comprising at least one or a plurality of artificial nucleic acid molecule(s), preferably NA(s), according to any one of claims 1 to 30 and a pharmaceutically acceptable carrier and / or excipient.

32. The composition according to claim 31, wherein at least two of said plurality of artificial nucleic acid molecules each (a) comprise the same or a different combination of UTR elements according to any one of claims 1 to 9 and / or (b) encode a different peptide or protein, optionally selected from a peptide or protein according to any one of claims 11 to 17.

33. The composition according to claim 31 or 32 for use as a medicament, optionally for use as a vaccine.

34. The (pharmaceutical) composition according to claim 33, preferably comprising at least one artificial nucleic acid molecule comprising a UTR combination according to claim 6, wherein said (pharmaceutical) composition and / or said artificial nucleic acid molecule is / are adapted for liver-targeted delivery.

35. The (pharmaceutical) composition according to claim 33, preferably comprising at least one artificial nucleic acid molecule comprising a UTR combination according to claim 7, wherein said (pharmaceutical) composition and / or said artificial nucleic acid molecule is / are adapted for subcutaneous, intracutaneous, intradermal, intradermal, topical or transdermal administration.

36. The (pharmaceutical) composition according to claim 33, preferably comprising at least one artificial nucleic acid molecule comprising a UTR combination according to claim 8, wherein said (pharmaceutical) composition and / or said artificial nucleic acid molecule is / are adapted for intramuscular administration.

37. The (pharmaceutical) composition or vaccine according to any one of claims 31 to 36, wherein the artificial nucleic acid molecule, preferably RNA, is complexed with one or more cationic or polycationic compounds, preferably with cationic or polycationic polymers, cationic or polycationic peptides or proteins, e.g. protamine, cationic or polycationic polysaccharides and / or cationic or polycationic lipids or polymeric carriers.

38. The (pharmaceutical) composition or vaccine according to claim 37, wherein the N / P ratio of the artificial nucleic acid molecule, preferably RNA, to the one or more cationic or polycationic peptides or proteins is in the range of about 0.1 to 10, including a range of about 0.3 to 4, of about 0.5 to 2, of about 0.7 to 2 and of about 0.7 to 1.5.

39. The (pharmaceutical) composition or vaccine according to any one of claims 31 to 38, wherein the artificial nucleic acid molecule, preferably RNA, is complexed with one or more lipids, thereby forming lipid nanoparticles, lipoplexes and / or preferably liposomes.

40. The (pharmaceutical) composition or vaccine according to any one of claims 31 to 39, further comprising at least one further active agent and / or at least one adjuvant.

41. The (pharmaceutical) composition or vaccine according to any one of claims 31 to 40, further comprising a non- coding RNA selected from the group consisting of small interfering RNA (siRNA), antisense RNA (asRNA), circular RNA (circRNA), ribozymes, aptamers, riboswitches, immunostimulating RNA (isRNA), transfer RNA (tRNA), ribosomal RNA (rRNA), small nuclear RNA (snRNA), small nucleolar RNA (snoRNA), microRNA (miRNA), and Piwi- interacting RNA (piRNA).

42. The (pharmaceutical) composition or vaccine according to claim 41, wherein the immunostimulating RNA (isRNA) comprises at least one RNA sequence according to formula (III) (G|XmG„), formula (IV) (QXmCn), formula (V) (NuG,XmGnNv)a, and / or formula (VI) (NuCiXmCnNv)a.

43. The (pharmaceutical) composition or vaccine of any one of claims 41 or 42, comprising a polymeric carrier cargo complex, formed by a polymeric carrier, preferably comprising disulfide-crosslinked cationic peptides, preferably Cys-Argl2, and / or Cys-Argl2-Cys, and an isRNA.

44. Kit, preferably kit of parts, comprising the artificial nucleic acid molecule, preferably RNA, according to any one of claims 1 to 30 or the (pharmaceutical) composition or vaccine according to any one of claims 31 to 43, and optionally a liquid vehicle and / or optionally technical instructions with information on the administration and dosage of the artificial nucleic acid molecule or the (pharmaceutical) composition or vaccine.

45. The kit according to claim 44, wherein the kit contains as a part Ringer-Lactate solution.

46. The artificial nucleic acid molecule, preferably RNA, according to any one of claims 1 to 30, the (pharmaceutical) composition or vaccine according to any one of claims 31 to 43, or the kit according to claim 44 or 45 for use as a medicament.

47. The artificial nucleic acid molecule, preferably RNA, according to any one of claims 1 to 30, the (pharmaceutical) composition or vaccine according to any one of claims 31 to 43, or the kit according to claim 44 or 45 for use in treating genetic diseases, cancer, infectious diseases, inflammatory diseases, (auto)immune diseases, allergies, and / or for use in gene therapy and / or immunomodulation.

48. The artificial nucleic acid molecule, preferably RNA, the (pharmaceutical) composition or vaccine or the kit for the use according to claim 47, wherein said use comprises (a) administering to a patient in need thereof said artificial nucleic acid molecule, preferably RNA, said (pharmaceutical) composition or said kit.

49. An artificial nucleic acid molecule, preferably RNA, according to any one of claims 6 to 30, the (pharmaceutical) composition or vaccine according to any one of claims 31 to 43, or the kit according to claim 44 or 45, said (pharmaceutical) composition or kit comprising at least one artificial nucleic acid molecule according to any one of claims 6 to 30, for use in a method of increasing the expression efficacy of said artificial nucleic acid molecule in liver tissue, liver cells, or liver cell lines.

50. An artificial nucleic acid molecule, preferably RNA, according to any one of claims 7 to 30, the (pharmaceutical) composition or vaccine according to any one of claims 31 to 43, or the kit according to claim 44 or 45, said (pharmaceutical) composition or kit comprising at least one artificial nucleic acid molecule according to any one of claims 7 to 30, for use in a method of increasing the expression efficacy of said artificial nucleic acid molecule in skin tissue, skin cells, or skin cell lines.

51. An artificial nucleic acid molecule, preferably RNA, according to any one of claims 8 to 30, the (pharmaceutical) composition or vaccine according to any one of claims 31 to 43, or the kit according to claim 44 or 45, said (pharmaceutical) composition or kit comprising at least one artificial nucleic acid molecule according to any one of claims 8 to 30, for use in a method of increasing the expression efficacy of said artificial nucleic acid molecule in muscular tissue, muscular cells, or muscular cell lines.

52. A method of treating or preventing a disorder optionally selected from genetic diseases, cancer, infectious diseases, inflammatory diseases, (auto)immune diseases, allergies, and / or for use in gene therapy and / or immunomodulation, wherein said method comprises administering to a subject in need thereof an effective amount of the artificial nucleic acid molecule, preferably RNA, according to any one of claims 1 to 30, the (pharmaceutical) composition or vaccine according to any one of claims 31 to 43, or the kit according to any one of claims 44 or 45.

53. A method for increasing the expression efficacy of an artificial nucleic acid molecule, preferably RNA, comprising at least one coding region encoding a protein or peptide preferably according to any one of claims 11 to 16, said method comprising(a) associating said coding region with a at least one 5' UTR element derived from a 5' UTR of a gene selected from the group consisting of HSD17B4, ASAH1, ATP5A1, MP68, NDUFA4, NOSIP, RPL31, SLC7A3, TUBB4B and UBQLN2, or from a corresponding RNA sequence, homolog, a fragment or a variant thereof;(b) associating said coding region with at least one 3' UTR element derived from a 3' UTR of a gene selected from the group consisting of PSMB3, CASP1, COX6B1, GNAS, NDUFA1 and RPS9, or from a corresponding RNA sequence, homolog, a fragment or a variant thereof; and(c) obtaining an artificial nucleic acid molecule, preferably RNA, according to any one of claims 1 to 30.

54. A method of identifying a combination of 5' UTR and 3' UTR capable of increasing the expression efficiency in a desired tissue or a cell derived from the desired tissue, comprising: a) generating a library of artificial nucleic acid molecules ("test constructs"), each comprising a "reporter ORF" encoding a detectable reporter polynucleotide, preferably selected luciferace or eGFP, operably linked to one of the 5' UTRs and / or one of the 3' UTRs as defined in claim 3; b) providing an artificial nucleic acid molecule comprising said "reporter ORF" operably linked to reference 5' and 3' UTRs, preferably RPL32 and ALB7 as a "reference construct"; c) introducing said test constructs and said reference constructs into the desired tissue or cell under suitable conditions allowing their expression; d) detecting and quantifying the expression of said polypeptide from the "reporter ORF" from the test constructs and the reference construct; e) comparing the polypeptide expression from the test constructs and reference constructs; wherein test constructs characterized by an increased polypeptide expression as compared to the reference construct are identified as being capable of increasing the expression efficiency in the desired tissue or cell.