LIPID NANOPARTICLES FOR NUCLEIC ACID DELIVERY

Abstract

The invention relates to novel cationic lipids and novel compositions comprising cationic lipids useful for the delivery of nucleic acids in living cells.

Description

LIPID NANOPARTICLES FOR DELIVERY OF NUCLEIC ACIDS BACKGROUND OF THE INVENTION The present invention relates to mRNA comprising lipid nanoparticles useful as mRNA-based vaccines. Furthermore, the present invention relates to a composition comprising the mRNA comprising lipid nanoparticles and the use of the mRNA comprising lipid nanoparticles or the composition for the preparation of a pharmaceutical composition, especially a vaccine, for example, for use in the prophylaxis or treatment of infectious diseases, tumor or cancer diseases, allergies or autoimmune diseases. The present invention further describes a method of treatment or prophylaxis of the aforementioned diseases. Gene therapy and genetic vaccination are among the most promising and rapidly developing methods in modern medicine. They can provide highly targeted and individualized treatment options for a wide variety of diseases. Genetic vaccination makes it possible to elicit a desired immune response to selected antigens, such as characteristic components of bacterial surfaces, viral particles, tumor antigens, or similar. Overall, vaccination is one of the fundamental achievements of modern medicine. However, effective vaccines are currently only available for a limited number of diseases. Consequently, infections that cannot be prevented by vaccination continue to affect millions of people each year. Vaccines can commonly be subdivided into “first,” “second,” and “third” generation vaccines. “First-generation” vaccines are typically whole-organism vaccines. They are based on live and attenuated or killed pathogens, for example, viruses, bacteria, or the like. The main drawback of live and attenuated vaccines is the risk of reversion to potentially fatal variants. Therefore, even if attenuated, such pathogens may still inherently carry unpredictable risks. Killed pathogens may not be as effective as desired in generating a specific immune response. To minimize these risks, “second-generation” vaccines have been developed. These are typically subunit vaccines, consisting of defined antigens or recombinant protein components derived from pathogens. Genetic vaccines, i.e., vaccines for genetic vaccination, are often referred to as "third-generation" vaccines. They typically consist of genetically engineered nucleic acid molecules that allow the expression of peptide or protein fragments (antigens) characteristic of a pathogen or tumor antigen in vivo. Genetic vaccines are expressed upon administration to a patient after uptake by target cells. Expression of the administered nucleic acids results in the production of the encoded proteins. If the patient's immune system recognizes these proteins as foreign, an immune response is triggered. DNA, as well as RNA, can be used as nucleic acid molecules for delivery in the context of genetic vaccination. DNA is known to be relatively stable and easy to manipulate. However, the use of DNA carries the risk of unwanted insertion of the administered DNA fragments into the patient's genome, which can lead to mutagenic events, such as the loss of function of damaged genes. As an additional risk, the unwanted generation of anti-DNA antibodies has emerged. Another drawback is the limited level of expression of the encoded peptide or protein that can be achieved with DNA administration because the DNA must enter the nucleus to be transcribed before the resulting mRNA can be translated. Among other reasons, the level of expression of the administered DNA will depend on the presence of specific transcription factors that regulate DNA transcription.In the absence of such factors, DNA transcription will not produce satisfactory amounts of RNA. As a result, the level of translated peptide or protein obtained is limited. By using RNA instead of DNA for genetic vaccination, the risk of unwanted genomic integration and the generation of anti-DNA antibodies is minimized or avoided. However, RNA is considered a rather unstable molecular species that can be easily degraded by ubiquitous RNAs. mRNA vaccines comprising mRNA encoding antigen complexed with protamine are already described in the prior art (e.g. PMID: 27336830 , PMID: 23159882 , EP1083232 , WO2010 / 037539 , WO2012 / 116811 , WO2012 / 116810 and WO2015 / 024665 ). Also WO2016 / 176330 describes lipid nanoparticle compositions comprising nucleoside-modified RNA encoding different antigens. Even though significant progress has been made in recent years, there is still a need in the field to provide an effective method for mRNA vaccination, capable of eliciting an adaptive immune response, where administration is not severely affected by early antigen degradation or inefficient mRNA translation due to inefficient mRNA release into the cell. Furthermore, there is an urgent need to reduce the dose of mRNA vaccines to reduce potential safety issues and make vaccines affordable for the developing world. There are many challenges associated with the delivery of nucleic acids to effect a desired response in a biological system. Nucleic acid-based therapies, such as vaccines, have enormous potential, but there remains a need for more efficient delivery of nucleic acids to appropriate sites within a cell or organism to realize this potential. However, two problems currently confront the use of nucleic acids in therapeutic contexts. First, free RNAs are susceptible to nuclease digestion in plasma. Second, free RNAs have a limited ability to access the intracellular compartment where the relevant translational machinery resides. Lipid nanoparticles formed from cationic lipids with other lipid components, such as neutral lipids, cholesterol, PEG, PEGylated lipids, and oligonucleotides, have been used to block RNA degradation in plasma and facilitate cellular uptake of oligonucleotides. There remains a need for improved cationic lipids and lipid nanoparticles for oligonucleotide delivery. Preferably, these lipid nanoparticles would provide optimal drug:lipid ratios, protect the nucleic acid from degradation and elimination in the serum, be suitable for systemic or local delivery, and provide intracellular delivery of the nucleic acid. Furthermore, these lipid-nucleic acid particles should be well tolerated and provide a MA / a / ¿U¿¿ / UU l oou therapeutically suitable, such that treatment of the patient with an effective dose of the nucleic acid is not associated with unacceptable toxicity and / or risk to the patient. The present invention provides these and other related advantages. BRIEF DESCRIPTION OF THE INVENTION In one aspect, the present invention relates to novel cationic lipids that are useful for the delivery of nucleic acids to living cells. Cationic lipids are compounds according to formula (I): Rs-A-Rbformula (I) where Rase selects from: -R1-N(H)-C(O)-R3-R4; Rbse is selected from: -R1-N(H)-C(O)-R3-R4, or -R1-N(CH3)2; A is -S-, -SS-, -SC(O)- -NH-C(O)-, -NH-C(O)O- -NH-C(O)-NH- -SC(O)N(H)- -C(O)O-, oOP(O)(OH)-O-; R1 is an optionally substituted linear or unbranched ethanedyl, propanedyl, butanedyl, or alkanedyl having 2 to 8 carbon atoms; R2 is an alkanedyl having 2 to 8 carbon atoms; R3 is optional, and if present, is -R5-C(O)-O-, or -R5-OC(O)-, -R5-C(O)-NH, -R5-OC(O)-NH-, or R5-NH-C(O)O-; R4 is a lipophilic substituent with 12 to 36 carbon atoms; R5 is an alkanedyl having 1 to 6 carbon atoms; X is a carbon or nitrogen atom; where all selections are independent of each other, optionally provided that if R1, R2, and R5 are all ethanedyl, A is -SS-, and Ray Rb are identical, then R4 is not > your NCNNCC σ α c In this respect, an alkanedyl is a term for a group (-CnH2n-); an “alkanedyl having from 2 to 8 carbon atoms” accordingly equals an alkanedyl group having the formula -C2H4-, C3H6-, -C4H8-, -C5H10-, -C6H12-, -C7H14-, or respectively -CsHie- In other words, an alkanedyl is a series of divalent radicals of the general formula CnH2n derived from aliphatic hydrocarbons. Unless otherwise specified, such alkanedyls include substituted alkanedyls. In another embodiment, in case R1, R2 and R5 are all ethanedyl, A is -SS-, and Rb are identical, then R4 is not υAL or । respectively in one embodiment, a lipid according to formula (I) is not the C23 lipid as described in Table 1 herein or, respectively, the SS-EC lipid as described herein below (for the avoidance of doubt, i.e., in some selected embodiments, the COATSOME® SS-EC cationic lipid is excluded from the embodiments that relate to the cationic lipids according to formula (I)). In another aspect, the invention provides novel compositions incorporating cationic lipids such as the novel cationic lipids defined above. Cationic lipids and compositions have been found to be particularly effective for introducing nucleic acids into living cells. For example, they enable enhanced RNA (e.g., mRNA) vaccines, i.e., mRNA-based vaccines against certain infectious diseases or tumors. In further aspects, the invention provides the use of compositions incorporating a cationic lipid and a nucleic acid compound as medicaments, and in particular as vaccines, as well as vaccination methods based on these vaccines. In another aspect of the present invention, the present invention also provides a kit, in particular a kit of parts, comprising the mRNA compound comprising the mRNA sequence as defined herein and at least one lipid according to formula (I) or formula (II) as defined herein. DEFINITIONS For the sake of clarity and readability, the following definitions and scientific background are provided. Any of the technical features mentioned or disclosed herein may be part of or read into each and every embodiment of the invention. Additional definitions and explanations may be provided within the context of this disclosure. Unless otherwise defined, or unless the specific context requires otherwise, all technical terms used in this document have the same meaning as commonly understood by a person skilled in the relevant technical field. Unless the context indicates or requires otherwise, the words “comprising,” “comprises,” and “comprising” and similar expressions are to be construed in an open and inclusive sense, such as “including, but not limited to,” in this description and in the claims. The terms “an embodiment,” “the embodiment,” “a specific embodiment,” and the like mean that a particular feature, property, or function, or a particular group or combination of features, properties, or functions, as referred to in combination with the respective term, is present in at least one of the embodiments of the invention. The appearance of these terms in various places throughout this description does not necessarily refer to the same embodiment. Furthermore, particular features, properties, or functions may be combined in any suitable manner in one or more embodiments. The singular forms “a,” “one,” “an,” “the,” and “the” should be understood to include plural references unless the context clearly indicates otherwise. Percentages in the context of numbers should be understood as relative to the total number of the respective articles. In all other cases, and unless the context indicates otherwise, percentages should be understood as percentages by weight (% by weight). As used herein, a “compound” means a chemical substance, which is a material consisting of molecules that have essentially the same chemical structure and properties. For a small molecular compound, the molecules are typically identical with respect to their atomic composition and structural configuration. For a macromolecular or polymeric compound, the molecules of a compound are very similar, but not all necessarily identical. For example, a segment of a polymer that is designated to consist of 50 monomer units may also contain individual molecules with, for example, 48 or 53 monomer units. The term “molecule” can be used as a synonym for “compound” or for an individual (i.e., a single) molecule. Any reference to a compound or fraction having a functional group that is ionizable under physiological conditions should be understood to include the ionized form of the respective compound or fraction. Vice versa, any reference to a compound or fraction having an ionized functional group that can also exist in a non-ionized form under physiological conditions should be understood to include the non-ionized form of the respective compound or fraction. For example, the description of a compound having a carboxyl group should be interpreted as a reference to the respective compound with a non-ionized carboxyl group or with the ionized carboxylate group. As used herein, “physiological conditions” refers to an aqueous environment having a pH that is within the known pH range of human physiology, including both extracellular and intracellular conditions. An approximation of this pH range is from about pH 1 to about pH 9. Depending on the context, physiological conditions may also refer to approximately neutral conditions, such as from about pH 5 to about pH 8.5, or from about pH 5.5 to about pH 8. A lipidoid compound, also referred to simply as a lipidoid, is a lipid-like compound, i.e., an amphiphilic compound with lipid-like physical properties. In the context of the present invention, the term lipid is considered to encompass lipidoids. In the context of the present invention, the term “selected from the group consisting of” followed by a certain group of elements (e.g., “A, B, and C”) is understood within the context of the invention not to be limited to said group. In other words, such a term does not indicate that the disclosure is closed to non-listed elements, i.e., alternative meanings are also included within the group following this term. Therefore, in the context of the present invention, the term “selected from the group consisting of” followed by a certain group of elements (e.g., “A, B, and C”) should be understood as “selected from A, B, and C” or alternatively “is A, B, or C which also encompasses other structurally and functionally related and unrelated but not mentioned elements. The term "approximately" is used when parameters or values ​​do not necessarily have to be identical, i.e., 100% equal. Accordingly, "approximately" means that a parameter or values ​​may differ by between 0.1% and 20%, preferably between 0.1% and 10%; in particular, by 0.5%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%. The skilled person will be aware that, for example, certain parameters or values ​​may vary slightly depending on the method used to determine the parameter. For example, if a certain parameter or value is defined here to have, for example, a length of “about 1000 nucleotides”, the length may vary between 0.1% and 20%, preferably between 0.1% and 10%; in particular, by 0.5%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%.Accordingly, the expert will know that in that specific example, the length may vary from 1 to 200 nucleotides, preferably from 1 to 100 nucleotides; in particular, by 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200 nucleotides. The term “cationic” means, unless a different meaning is implied by the specific context, that the respective structure carries a positive charge, either permanently or non-permanently, but in response to certain conditions such as, for example, pH. Therefore, the term “cationic” covers both “permanently cationic” and “cationizable.” The term “cationizable,” as used herein, means that a compound, group, or atom is positively charged at a lower pH and discharged at a higher pH of its environment. Also in non-aqueous environments where the pH value cannot be determined, a cationizable compound, group, or atom is positively charged at a high hydrogen ion concentration and discharged at a low hydrogen ion concentration or activity.It depends on the individual properties of the cationizable or polycationizable compound, in particular the pKa of the respective cationizable group or atom, at whose pH or hydrogen ion concentration it is charged or uncharged. In dilute aqueous media, the fraction of cationizable compounds, groups, or atoms that carry a positive charge can be estimated using the so-called equation. IVIA / a / ZUZZ / UU / oou of Henderson-Hasselbalch, well known to those skilled in the art. For example, if a compound or fraction is cationizable, it is preferred that it is positively charged at a pH value of about 1 to 9, preferably 4 to 9, 5 to 8 or even 6 to 8, more preferably at a pH value of or below 9, of or below 8, of or below 7, most preferably at physiological pH values, for example, of about 7.3 to 7.4, that is, under physiological conditions, particularly under physiological salt conditions of the cell in vivo. In embodiments, it is preferred that the cationizable compound or fraction is predominantly neutral at physiological pH values, for example, about 7.0 to 7.4, but is positively charged at lower pH values. In some embodiments, the preferred range of pKa for the cationizable compound or fractionation is from about 5 to about 7.In some embodiments, protonatable lipids have a pKa of the protonatable group in the range of about 4 to about 11, e.g., a pKa of about 5 to about 7. In some embodiments, protonatable lipids have a pKa of the protonatable group in the range of about 4 to about 11, e.g., a pKa of about 5 to about 7. Unless otherwise stated in the specific context, the term "cationic" means that the respective structure has a positive charge, either permanently or non-permanently, but in response to certain conditions, such as pH. Therefore, the term "cationic" encompasses both "permanently cationic" and "cationizable." For example, a compound or moiety with a primary, secondary, or tertiary amino group is cationic and, more specifically, cationizable, since it can exist predominantly in a positively charged state under physiological conditions. As used herein, “permanently cationic” means that the compound, or respective group or atom, is positively charged at any pH value or hydrogen ion activity of its environment. Most often, the positive charge results from the presence of a quaternary nitrogen atom. When a compound carries a plurality of such positive charges, it may be referred to as a permanently polycationic, which is a subcategory of permanently cationic. Similarly, the terms “anionic,” “anionizable,” and “permanently anionic” have the analogous meaning of “cationic,” “cationizable,” and “permanently cationic,” except that the charge of the respective compound, group, or atom is negative rather than positive. The expression “neutral”, when applied to a compound such as a lipid or a spheroid, or to a group or fraction, means that it is neither cationic nor anionic, such as a compound having no functional groups that are ionizable under physiological conditions, such as a hydrocarbon; or it is both cationic and anionic, i.e., zwitterionic, under typical physiological conditions, such as a typical native phosphatidylicholine. A “lipid,” as used herein, refers to a group of organic compounds that are derivatives of fatty acids (e.g., esters) and are generally characterized by being insoluble in water but soluble in many organic solvents. Lipids are generally divided into at least three classes: (1) “simple lipids,” which include fats and oils, as well as waxes; (2) “compound lipids,” which include phospholipids and glycolipids; and (3) “derived lipids,” such as spheroids. With respect to glycolipids, in certain embodiments, the LNP comprises glycolipids (e.g., monosialoganglioside GMi). i oou In this context, the prefix "poly-" refers to a plurality of atoms or groups that have the respective property in a compound. If enclosed in parentheses, the presence of a plurality is optional. For example, (poly)cationic means cationic and / or polycationic. However, the absence of the prefix should not be interpreted as excluding a plurality. For example, a polycationic compound is also a cationic compound and may be referred to as such. The term “nucleic acid” means any compound comprising or consisting of DNA or RNA. The term may be used for a polynucleotide and / or oligonucleotide. Whenever reference is made herein to a nucleic acid or nucleic acid sequence encoding a particular protein and / or peptide, said nucleic acid or nucleic acid sequence, respectively, preferably also comprises regulatory sequences that allow its expression in a suitable host, for example, a human, i.e., the transcription and / or translation of the nucleic acid sequence encoding the particular protein or peptide. In the context of the present invention, the term “nucleoside modification” refers to nucleic acids such as mRNA compounds or molecules comprising nucleosides not normally found in native mRNA, preferably non-natural nucleosides. In particular, the term preferably refers to mRNA nucleosides other than adenine, guanine, cytosine, uracil, and thymine. The term "nucleoside" generally refers to compounds consisting of a sugar, usually ribose or deoxyribose, and a purine or pyrimidine base. The term "nucleotide" generally refers to a nucleoside comprising a phosphate group attached to the sugar. A "peptide" means an oligomer or polymer of at least two amino acid monomers linked by peptide bonds. The term does not limit the length of the amino acid polymer chain. A peptide may, for example, contain fewer than 50 monomer units. Longer peptides are also called polypeptides and typically have 50 to 600 monomer units, more specifically 50 to 300 monomer units. A “protein” comprises or consists of one or more polypeptides folded into a three-dimensional shape, which facilitates a biological function. A “pandemic influenza” or “pandemic flu” can occur when a non-human (novel) influenza virus acquires the ability to transmit efficiently and sustainably from person to person and then spreads globally. Influenza viruses that have the potential to cause a pandemic are called “influenza viruses with pandemic potential” or “pandemic influenza viruses.” Examples of influenza viruses with pandemic potential include avian influenza A (H5N1) and avian influenza A (H7N9), which are two different “bird flu” viruses. These are non-human viruses (i.e., they are new to humans and circulate among birds in some parts of the world), so there is little or no immunity against these viruses among people. Human infections with these viruses have rarely occurred, but if either of these viruses were to change in such a way that it could easily infect humans and spread easily from person to person, an influenza pandemic could result. IVIA / S / ZUZZ / UU / oou Pandemic influenza / flu vaccine or pandemic influenza / flu vaccine: A vaccine directed against a pandemic influenza virus is referred to herein as a pandemic influenza / flu vaccine or pandemic influenza / flu vaccine. Flu / Influenza Season: Flu season is a recurring annual period characterized by the prevalence of influenza (flu) outbreaks. The season occurs during the cold half of the year in each hemisphere. Influenza activity can sometimes be predicted and even tracked geographically. While the onset of major flu activity each season varies by location, in any specific location, these minor epidemics generally take about 3 weeks to peak and another 3 weeks to significantly decline. Flu vaccines have been used to lessen the effects of flu season; pneumonia vaccines also reduce the effects and complications of flu season. Since the Northern and Southern Hemispheres experience winter at different times of the year, there are actually two flu seasons each year. Seasonal influenza / flu vaccine or seasonal influenza / flu vaccine: A vaccine directed against seasonal influenza viruses that occur during a flu season is referred to herein as “seasonal influenza / flu vaccine or seasonal influenza / flu vaccine.” Immune system: The immune system can protect organisms from infection. If a pathogen crosses an organism's physical barrier and enters it, the innate immune system provides an immediate, but nonspecific, response. If pathogens evade this innate response, vertebrates possess a second layer of protection, the adaptive immune system. Here, the immune system adapts its response during an infection to improve its recognition of the pathogen. This enhanced response is then retained after the pathogen has been eliminated, in the form of immunological memory, and allows the adaptive immune system to mount faster and stronger attacks each time it encounters that pathogen. According to this, the immune system comprises the innate and adaptive immune systems. Immune response: An immune response can typically be a specific reaction of the adaptive immune system to a particular antigen (the so-called specific or adaptive immune response) or a nonspecific reaction of the innate immune system (the so-called nonspecific or innate immune response). The invention relates to the core of specific reactions (adaptive immune responses) of the adaptive immune system. In particular, it relates to adaptive immune responses to infections by viruses such as influenza viruses. However, this specific response can be supported by an additional nonspecific reaction (innate immune response). Therefore, the invention also relates to a compound for the simultaneous stimulation of the innate and adaptive immune systems to elicit an effective adaptive immune response. Adaptive immune system: The adaptive immune system is composed of highly specialized cells and systemic processes that eliminate or prevent pathogen growth. The adaptive immune response provides the vertebrate immune system with the ability to recognize and remember specific pathogens (to generate immunity) and to mount stronger attacks each time it encounters them. MA / a / ¿U¿¿ / UU l oou with the pathogen. The system is highly adaptable due to somatic hypermutation (a process of increased frequency of somatic mutations) and V(D)J recombination (an irreversible genetic recombination of antigen receptor gene segments). This mechanism allows a small number of genes to generate a large number of different antigen receptors, which are then uniquely expressed in each individual lymphocyte. Because the gene rearrangement leads to an irreversible change in the DNA of each cell, all progeny (offspring) of that cell will inherit genes encoding the same receptor specificity, including the memory B cells and memory T cells that are the keys to long-lasting specific immunity.Immune network theory is a theory of how the adaptive immune system works, based on the interactions between the variable regions of T cell receptors, B cells, and molecules made by T cells and B cells that have variable regions. Adaptive immune response: The adaptive immune response is typically understood to be antigen-specific. Antigen specificity allows for the generation of responses that are tailored to specific antigens, pathogens, or pathogen-infected cells. The ability to mount these personalized responses is maintained in the body by “memory cells.” If a pathogen infects the body more than once, these specific memory cells are used to rapidly eliminate it. In this context, the first step of an adaptive immune response is the activation of antigen-specific naive T cells or different immune cells capable of inducing an antigen-specific immune response by antigen-presenting cells. This occurs in lymphoid tissues and organs through which naive T cells constantly pass.Cell types that can serve as antigen-presenting cells include dendritic cells, macrophages, and B cells. Each of these cells has a distinct role in eliciting immune responses. Dendritic cells take up antigens by phagocytosis and macropinocytosis and are stimulated by contact with, for example, a foreign antigen to migrate to the local lymphoid tissue, where they differentiate into mature dendritic cells. Macrophages ingest particulate antigens such as bacteria and are induced by infectious agents or other appropriate stimuli to express MHC molecules. The unique ability of B cells to bind and internalize soluble protein antigens through their receptors may also be important for inducing T cells. Antigen presentation on MHC molecules leads to T cell activation, which induces their proliferation and differentiation into armed effector T cells.The most important function of T effector cells is the destruction of infected cells by CD8+ cytotoxic T cells and the activation of macrophages by Th1 cells which together form cell-mediated immunity, and the activation of B cells by Th2 and Th1 cells to produce different classes of antibodies, thus boosting the humoral immune response. T cells recognize an antigen by their T cell receptors which do not recognize or bind the antigen directly, but recognize short peptide fragments, e.g., protein antigens derived from pathogens, which bind to MHC molecules on the surface of other cells. Cellular immunity / cellular immune response: Cellular immunity is typically related to the activation of macrophages, natural killer (NK) cells, antigen-specific cytotoxic T lymphocytes IVIA / a / ZUZZ / UU l oou and the release of various cytokines in response to an antigen. More generally, cellular immunity is not related to antibodies but to the activation of cells of the immune system. A cellular immune response is characterized, for example, by the activation of antigen-specific cytotoxic T lymphocytes that can induce apoptosis in body cells that display epitopes of an antigen on their surface, such as cells infected by viruses, cells with intracellular bacteria, and cancer cells displaying tumor antigens; activate macrophages and natural killer cells, allowing them to destroy pathogens; and stimulate cells to secrete a variety of cytokines that influence the function of other cells involved in adaptive immune responses and innate immune responses. Humoral immunity / humoral immune response: Humoral immunity typically refers to antibody production and the accessory processes that may accompany it. A humoral immune response may typically be characterized, for example, by Th2 activation and cytokine production, germinal center formation and isotype switching, affinity maturation, and generation of memory cells. Humoral immunity may also typically refer to the effector functions of antibodies, which include neutralization of pathogens and toxins, classical complement activation, and promotion of phagocytosis and opsonin-mediated pathogen killing. Innate immune system: The innate immune system, also known as the nonspecific immune system, comprises the cells and mechanisms that defend the host against infection by other organisms in a nonspecific manner. This means that the cells of the innate immune system recognize and respond to pathogens generically, but unlike the adaptive immune system, they do not confer protective or long-lasting immunity to the host. The innate immune system can be activated, for example, by pathogen-associated molecular pattern receptor (PAMP) ligands, e.g., Toll-like receptors (TLRs), or other helper substances such as lipopolysaccharides, TNF-alpha, CD40 ligand, or cytokines, monokines, lymphokines., interleukins or chemotherapeutics, IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL12, IL-13, IL-14, IL-15, IL-16, IL-17, IL-18, IL-19, IL-20, IL-21, IL-22, IL-23, IL-24, IL-25, IL-26, IL-27, IL-28, IL29, IL-30, IL-31, IL-32, IL-33, IFN-alpha, IFN-beta, IFN-gamma, GM-CSF, G-CSF, M-CSF, LT-beta, TNF-alpha, growth factors and hGH, a ligand of the human Toll-like receptor TLR1, TLR2, TLR3, TLR4, TLR5, TLR6, TLR7, TLR8, TLR9, TLR10, a murine Toll-like receptor ligand TLR1, TLR2, TLR3, TLR4, TLR5, TLR6, TLR7, TLR8, TLR9, TLR10, TLR11, TLR12 or TLR13, a NOD-like receptor ligand, a receptor similar to RIG-I, an immunostimulant nucleic acid, an immunostimulant ARN (ARNis), an ADN-CpG, an antibacterial agent or an antiviral agent.Typically, an innate immune system response includes the recruitment of immune cells to sites of infection through the production of chemical factors, including specialized chemical mediators called cytokines; activation of the complement cascade; identification and elimination of foreign substances present in organs, tissues, blood, and lymph by specialized white blood cells; activation of the adaptive immune system through a process known as antigen presentation; and / or acting as a physical and chemical barrier to infectious agents. Adjuvant / Adjuvant Component: An adjuvant or adjuvant component in the broadest sense is typically an agent or composition (e.g., pharmacological or immunological) that can modify, e.g., enhance, the efficacy of other agents, such as a drug or a vaccine. Conventionally, the term refers in the context of the invention to a compound or composition that serves as a carrier or auxiliary substance for immunogens and / or other pharmaceutically active compounds. It should be interpreted broadly and refers to a broad spectrum of substances that can enhance the immunogenicity of antigens incorporated into or co-administered with an adjuvant in question. In the context of the present invention, an adjuvant will preferably enhance the specific immunogenic effect of the active agents of the present invention. Typically, “adjuvant” or “adjuvant component” have the same meaning and may be used interchangeably.Adjuvants can be divided, for example, into immunopotentiators, antigen delivery systems, or even combinations thereof. The term “adjuvant” is generally understood not to encompass agents that confer immunity in and of themselves. An adjuvant helps the immune system in a nonspecific manner to enhance the antigen-specific immune response, for example, by promoting the presentation of an antigen to the immune system or the induction of a nonspecific innate immune response. Furthermore, an adjuvant may preferentially, for example, modulate the antigen-specific immune response, e.g., by shifting the dominant Th2-based antigen-specific response to a more Th1-based antigen-specific response or vice versa. Accordingly, an adjuvant may favorably modulate cytokine expression / secretion, antigen presentation, the type of immune response, etc. Immunostimulatory RNA: An immunostimulatory RNA (mRNA) in the context of the invention can typically be an RNA that is capable of inducing an innate immune response by itself. It usually does not have an open reading frame and therefore does not deliver a peptide antigen or immunogen, but rather elicits an innate immune response, for example, by binding to a specific type of Toll-like receptor (TLR) or other suitable receptors. However, of course, mRNAs that have an open reading frame and encode a peptide / protein (e.g., an antigenic function) can also induce an innate immune response. The term “antibody,” as used herein, includes both an intact antibody and an antibody fragment. Generally, an intact “antibody” is an immunoglobulin that specifically binds to a particular antigen. An antibody can be a member of any immunoglobulin class, including any of the human classes: IgG, IgM, IgE, IgA, and IgD. Typically, an intact antibody is a tetramer. Each tetramer consists of two identical pairs of polypeptide chains, each pair having a “light” chain and a “heavy” chain. An “antibody fragment” includes a portion of an intact antibody, such as the variable or antigen-binding region of an antibody. Examples of antibody fragments include Fab, Fab', F(ab')2, and Fv fragments; the tribes; tetra; linear antibodies; single-chain antibody molecules; and multispecific antibodies formed from antibody fragments.For example, antibody fragments comprise isolated fragments, “Fv” fragments consisting of heavy and light chain variable regions, recombinant single chain polypeptide molecules in which the heavy and light chain variable regions are linked together by a peptide linker (“ScFv proteins”), and minimal recognition units consisting of amino acid residues that mimic the hypervariable region. Examples of antigen-binding fragments of an antibody include, but are not limited to, Fab fragment, Fab' fragment, F(abj2) fragment, scFv fragment, Fv fragment, dsFv diabody, dAb fragment, Fd' fragment, Fd fragment, and an isolated complementarity determining region (CDR).Suitable antibodies that may be encoded by the therapeutic RNA of the invention include monoclonal antibodies, polyclonal antibodies, mixtures or cocktails of antibodies, human or humanized antibodies, chimeric antibodies, Fab fragments, or bispecific antibodies. In the context of the invention, the at least one therapeutic RNA of the combination / composition of the invention may provide an antibody. The term “antigen” in the context of the present invention typically refers to a substance that can be recognized by the immune system, preferably by the adaptive immune system, and is capable of triggering an antigen-specific immune response, for example by the formation of antibodies, and / or antigen-specific T cells as part of an adaptive immune response. Typically, an antigen may be or may comprise a peptide or protein that can be presented by the MHC to T cells. In the sense of the present invention, an antigen may be the translation product of a provided nucleic acid molecule, preferably an mRNA as defined herein. In this context, antigen is also understood to mean fragments, variants and derivatives of peptides and proteins comprising at least one epitope.Respectively, the term “antigen” as used herein will be recognized and understood by the person skilled in the art and, for example, refers to a substance that can be recognized by the immune system, preferably by the adaptive immune system, and is capable of triggering an antigen-specific immune response, for example, by the formation of antibodies and / or antigen-specific T cells as part of an adaptive immune response. Typically, an antigen may be or may comprise a peptide or protein that can be presented by the MHC to T cells. Antigens may also be understood as fragments, variants and derivatives of peptides or proteins derived from, for example, cancer antigens comprising at least one epitope. In the context of the present invention, an antigen may be the translation product of a provided therapeutic RNA (for example, coding RNA, replicon RNA, mRNA).The term “antigenic peptide or protein” will be recognized and understood by those skilled in the art and, for example, is intended to refer to a peptide or protein derived from an (antigenic) protein that can stimulate the body's adaptive immune system to provide an adaptive immune response. Therefore, an “antigenic peptide or protein” comprises at least one epitope or antigen of the protein from which it is derived (e.g., a tumor antigen, a viral antigen, a bacterial antigen, a protozoan antigen). In the context of the invention, the at least one therapeutic RNA of the combination / composition of the invention may provide an antigen. is intended to refer to a peptide or protein derived from an (antigenic) protein that can stimulate the body's adaptive immune system to provide an adaptive immune response.Thus, an “antigenic peptide or protein” comprises at least one epitope or antigen of the protein from which it is derived (e.g., a tumor antigen, a viral antigen, a bacterial antigen, a protozoan antigen). In the context of the invention, the at least one therapeutic RNA in the combination / composition of the invention may provide an antigen. The term “antigenic peptide” or “antigenic protein” is intended to refer to a peptide or protein derived from an (antigenic) protein that can stimulate the body’s adaptive immune system to provide a response. IVIA / a / ¿U¿¿ / UU l oou adaptive immune. Therefore, an “antigenic peptide or protein” comprises at least one epitope or antigen of the protein from which it is derived (e.g., a tumor antigen, a viral antigen, a bacterial antigen, a protozoan antigen). In the context of the invention, the at least one therapeutic RNA of the combination / composition of the invention may provide an antigen. The term “derived from” as used throughout this specification in the context of a nucleic acid, i.e., for a nucleic acid “derived from” (another) nucleic acid, means that the nucleic acid, being derived from (another) nucleic acid, shares, for example, at least about 50%, 60%, 70%, 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or about 99% sequence identity with the nucleic acid from which it is derived. The person skilled in the art is aware that sequence identity is typically calculated for the same types of nucleic acids, i.e., for DNA sequences or for RNA sequences.It is therefore understood that 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 U with T throughout the sequence) or, vice versa, the DNA sequence is converted into the corresponding RNA sequence (in particular by replacing T with U throughout the sequence). Subsequently, 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 a nucleic acid that is modified compared to the nucleic acid from which it is derived, for example, to further increase the stability of the RNA and / or to prolong and / or increase protein production.In the context of amino acid sequences, the term “derived from” means that the amino acid sequence, which is derived from (another) amino acid sequence, shares, for example, at least about 70%, 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or about 99% sequence identity with the amino acid sequence from which it is derived. Epitope (also called “antigen determinant”): T cell epitopes or parts of proteins in the context of the present invention may comprise fragments preferably having a length of about 6 to about 20 or even more amino acids, e.g. fragments as processed and presented by MHC class I molecules, preferably having a length of about 8 to about 10 amino acids, e.g. 8, 9 or 10 (or even 11 or 12 amino acids), or fragments processed and presented by MHC class II molecules, preferably having a length of about 13 or more amino acids, e.g. 13, 14, 15, 16, 17, 18, 19, 20 or even more amino acids, where these fragments may be selected from any part of the amino acid sequence. These fragments are usually recognized by T cells in the form of a complex consisting of the peptide fragment and an MHC molecule. B cell epitopes are typically fragments located on the external surface of (native) protein or peptide antigens as defined herein, preferably having 5 to 15 amino acids, more preferably having 5 to 12 amino acids, even more preferably having 6 to 9 amino acids, which can be recognized by antibodies, i.e. in their native form. MA / a / ¿U¿¿ / UU l oou Such protein or peptide epitopes may further be selected from any of the variants mentioned herein of such proteins or peptides. In this context, the antigenic determinants may be conformational or discontinuous epitopes that are composed of segments of proteins or peptides as defined herein that are discontinuous in the amino acid sequence of the proteins or peptides as defined herein but are joined in the three-dimensional structure, or continuous or linear epitopes that are composed of a single polypeptide chain. The term "vaccine" is generally understood to mean a prophylactic or therapeutic material that provides at least one antigen or antigenic function. The antigen or antigenic function can stimulate the body's adaptive immune system to produce an adaptive immune response. The term “antigen-providing mRNA” in the context of the invention may typically be an mRNA, which has at least one open reading frame that can be translated by a cell or organism provided with that mRNA. The product of this translation is a peptide or protein that can act as an antigen, preferably as an immunogen. The product may also be a fusion protein composed of more than one immunogen, for example, a fusion protein consisting of two or more epitopes, peptides, or proteins derived from the same or different viral proteins, where the epitopes, peptides, or proteins may be linked by linker sequences. The term “artificial mRNA” (sequence) can usually be understood as an mRNA molecule that does not occur naturally. In other words, an artificial mRNA molecule can be understood as a non-natural mRNA molecule. Such an mRNA molecule may not be natural due to its individual sequence (which does not occur naturally) and / or due to other modifications, for example, structural modifications of nucleotides that do not occur naturally. Typically, artificial mRNA molecules can be designed and / or generated by genetic engineering methods to correspond to a desired artificial nucleotide sequence (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” can be understood as a sequence that occurs in nature.Furthermore, the term "artificial nucleic acid molecule" is not limited to "a single molecule" but is typically understood to comprise a set of identical molecules. Consequently, it can refer to a plurality of identical molecules contained in an aliquot. The terms “heterologous” or “heterologous sequence,” as used herein in the context of a nucleic acid sequence or an amino acid sequence, refer to a sequence (e.g., DNA, RNA, amino acid) that will be recognized and understood by one of ordinary skill in the art, and are intended to refer to a sequence that is derived from another gene, another allele, or another species. Two sequences are typically understood to be “heterologous” if they are not derived from the same gene or on the same allele. That is, although heterologous sequences may be derived from the same organism, they are not naturally (in nature) found on the same nucleic acid molecule, such as the same RNA or protein. Bi- / multicistronic mRNA: An mRNA that typically has two (bicistronic) or more (multicistronic) open reading frames (ORFs) (coding regions or coding sequences). An open reading frame in this context is a sequence of several nucleotide triplets (codons) that can be translated into a peptide or protein. Translation of such an mRNA produces two (bicistronic) or more (multicistronic) distinct translation products (provided the ORFs are not identical). For expression in eukaryotes, such mRNAs may comprise, for example, an internal ribosomal entry site (IRES) sequence. Monocistronic mRNA: A monocistronic mRNA is typically an mRNA that comprises only one open reading frame (coding sequence or coding region). An open reading frame in this context is a sequence of several nucleotide triplets (codons) that can be translated into a peptide or protein. 3'-untranslated region (3'-UTR): A 3'-UTR is typically the part of an mRNA that lies between the protein-coding region (i.e., the open reading frame) and the poly(A) sequence of the mRNA. A 3'-UTR of mRNA is not translated into an amino acid sequence. The 3'-UTR sequence is usually encoded by the gene which is transcribed into the respective mRNA during the process of gene expression. The genomic sequence is first transcribed into pre-mature mRNA, which comprises optional introns. The pre-mature mRNA is then further processed into mature mRNA in a maturation process. This maturation process comprises the steps of 5'-capping, splicing of pre-mature mRNA to remove optional introns, and 3'-end modifications such as polyadenylation of the 3' end of pre-mature mRNA and endo- or exonuclease cleavages, etc.In the context of the present invention, a 3'-UTR corresponds to the sequence of a mature mRNA that is located 3' of the termination codon n of the protein-coding region, preferably immediately 3' of the termination codon of the protein-coding region, and that extends to the 5' side of the poly(A) sequence, preferably to the nucleotide immediately 5' to the poly(A) sequence. The term “corresponds to” means that the 3'-UTR sequence may be an RNA sequence, as in the mRNA sequence used to define the 3'-UTR sequence, or a DNA sequence corresponding to said RNA sequence. In the context of the present invention, the term “a 3'-UTR of a gene,” such as “a 3'-UTR of an albumin gene,” is the sequence that corresponds to the 3'-UTR of the mature mRNA derived from that gene, i.e. the mRNA obtained by transcription of the gene and maturation of the premature mRNA.The term “3'-UTR of a gene” encompasses both the DNA sequence and the RNA sequence of the 3'-UTR. 5'-untranslated region (5'-UTR): A 5'-UTR is typically understood as a particular section of messenger RNA (mRNA). It is located 5' of the open reading frame of the mRNA. Typically, the 5'-UTR begins with the transcription start site and ends one nucleotide before the start codon of the open reading frame. The 5'-UTR may comprise gene expression control elements, also called regulatory elements. Such regulatory elements may be, for example, ribosomal binding sites or a 5'-Terminal Oligopyrimidine Tract. The 5'-UTR may be post-transcriptionally modified, for example by the addition of a 5'-CAP. In the context of the present invention, a 5'-UTR corresponds to the sequence of a mature mRNA that is located between the 5'-CAP and the start codon.Preferably, the 5'-UTR corresponds to the sequence extending 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 site of the protein-coding region, preferably to the nucleotide located immediately 5' to the start site of the protein-coding region. The nucleotide located immediately 3' to the 5'-CAP of a mature mRNA typically corresponds to the transcription start site. The term “corresponds to” means that the 5'-UTR sequence can be an RNA sequence, as in the mRNA sequence used to define the 5'-UTR sequence, or a DNA sequence corresponding to such RNA sequence.In the context of the present invention, the term “a 5'-UTR of a gene,” such as “a 5'-UTR of a TOP gene,” is the sequence corresponding to the 5'-UTR of the mature mRNA derived from that gene, i.e., the mRNA obtained by transcription of the gene and maturation of the premature mRNA. The term “5'-UTR of a gene” encompasses both the DNA sequence and the RNA sequence of the 5'-UTR. 5'-terminal oligopyrimidine tract (TOP): The 5'-terminal oligopyrimidine tract (TOP) is typically a stretch of pyrimidine nucleotides located at 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 sequence begins with a cytidine, which usually corresponds to the transcription start site, and is followed by a stretch of about 3 to 30 pyrimidine nucleotides. For example, the 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. The pyrimidine stretch and therefore the 5'-TOP terminates one nucleotide 5' to the first purine nucleotide located downstream of the TOP. Messenger RNA containing a 5'-terminal oligopyrimidine stretch is often referred to as TOP mRNA.Consequently, the genes that provide such messenger RNAs are called TOP genes. TOP sequences have been found, for example, in genes and mRNAs encoding peptide elongation factors and ribosomal proteins. TOP motif: In the context of the present invention, a TOP motif is a nucleic acid sequence corresponding to a 5'-TOP as defined above. Thus, a TOP motif in the context of the present invention is preferably a stretch of pyrimidine nucleotides having a length of 3-30 nucleotides. Preferably, the TOP motif consists of at least 3 pyrimidine nucleotides, preferably at least 4 pyrimidine nucleotides, preferably at least 5 pyrimidine nucleotides, more preferably at least 6 nucleotides, more preferably at least 7 nucleotides, most preferably at least 8 pyrimidine nucleotides, where the stretch of pyrimidine nucleotides preferably begins at its 5' end with a cytosine nucleotide. In TOP genes and TOP mRNA, the TOP motif preferably begins at its 5' end with the transcriptional start site and ends one nucleotide 5' to the first purine residue in that gene or mRNA.A TOP motif within the meaning of the present invention is preferably located at the 5' end of a sequence representing a 5'-UTR or at the 5' end of a sequence encoding a 5'-UTR. Thus, preferably, a stretch of 3 or more pyrimidine nucleotides is referred to as a “TOP motif” within the meaning of the present invention if this stretch is located at the 5' end of a respective sequence, such as the mRNA of the invention, the 5'-UTR element of the inventive mRNA, or the nucleic acid sequence that is derived from the 5'-UTR of a TOP gene as described herein. In other words, a stretch of 3 or more pyrimidine nucleotides that is not found at the 5' end of a 5'-UTR or a 5'-UTR element but elsewhere within a 5'-UTR or a 5'-UTR element is preferably not referred to as a “TOP motif”. TOP gene: TOP genes are typically characterized by the presence of a 5'-terminal oligopyrimidine tract. In addition, most TOP genes are characterized by growth-associated translational regulation. However, TOP genes with tissue-specific translational regulation are also known. As defined above, the 5'-UTR of a TOP gene corresponds to the sequence of a 5'-UTR of a mature mRNA derived from a TOP gene, preferably extending from the nucleotide located 3' to the 5'-CAP to the nucleotide located 5' of the start codon. 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). In this, upstream AUGs and upstream open reading frames are typically understood as AUGs and open reading frames occurring 5' of the start codon (AUG) of the open reading frame to be translated.The 5'-UTRs of TOP genes are generally quite short. The lengths of the 5'-UTRs of TOP genes can vary between 20 nucleotides and 500 nucleotides, and are usually less than 200 nucleotides, preferably less than 150 nucleotides, more preferably less than 100 nucleotides. Examples of 5'-UTRs of TOP genes within the meaning of the present invention are the nucleic acid sequences extending from the nucleotide at position 5 to the nucleotide located immediately 5' to the start codon (e.g. the ATG) in the sequences according to SEO ID NO: 1-1363, SEO ID NO: 1395, SEO ID NO: 1421 and SEO ID NO: 1422 of international patent application WO2013 / 143700 or homologues or variants thereof, the disclosure of which is incorporated herein by reference. In this context, a particularly preferred fragment of a 5'-UTR of a TOP gene is a 5'-UTR of a TOP gene lacking the 5'-TOP motif.The term “5'-UTR of a TOP gene” preferably refers to the 5'-UTR of a naturally occurring TOP gene. Fragment of a nucleic acid sequence, particularly an mRNA: A fragment of a nucleic acid sequence consists of a continuous stretch of nucleotides corresponding to a continuous stretch of nucleotides in the full-length nucleic acid sequence that is the basis for the nucleic acid sequence of the fragment, 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%, even more preferably at least 80%, and most preferably at least 90% of the full-length nucleic acid sequence. Such a fragment, within the meaning of the present invention, is preferably a functional fragment of the full-length nucleic acid sequence. In the context of the present invention, a “fragment” or “variant” of a protein or peptide may have at least 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% amino acid identity over a stretch of at least 10, at least 20, at least 30, at least 50, at least 75 or at least 100 amino acids of said protein or peptide. More preferably, a “fragment” or “variant” of a protein or peptide as used herein is at least 40%, preferably at least 50%, more preferably at least 60%, more preferably at least 70%, even more preferably at least 80%, even more preferably at least 90%, most preferably at least 95% identical to the protein or peptide, Variant of a nucleic acid sequence, particularly an mRNA: A variant of a nucleic acid sequence refers to a variant of nucleic acid sequences that forms the basis of a nucleic acid sequence. For example, a variant nucleic acid sequence may exhibit one or more nucleotide deletions, insertions, additions and / or substitutions compared to the nucleic acid sequence from which the variant is derived. Preferably, a variant of a nucleic acid sequence is at least 40%, preferably at least 50%, more preferably at least 60%, more preferably at least 70%, even more preferably at least 80%, still more preferably at least 90%, most preferably at least 95% identical to the nucleic acid sequence from which the variant is derived. Preferably, the variant is a functional variant.A “variant” of a nucleic acid sequence may have at least 70%, 75%, 80%, 85%, 90%, 95%, 98%, or 99% sequence identity over a 10, 20, 30, 50, 75, or 100 nucleotide stretch of said nucleic acid sequence. Stabilized nucleic acid, preferably mRNA: A stabilized nucleic acid, preferably mRNA, typically exhibits a modification that increases resistance to in vivo degradation (e.g., exonuclease or endonuclease degradation) and / or ex vivo degradation (e.g., by the manufacturing process prior to administration of the vaccine, e.g., in the course of preparing the vaccine solution to be administered). Stabilization of the RNA can be achieved, for example, by providing a 5'-CAP structure, a polyA tail, or any other UTR modification. It can also be achieved by chemical modification or modification of the G / C content of the nucleic acid. Various other methods are known in the art and are conceivable within the context of the invention. In vitro transcription of RNA: The terms “in vitro transcription of RNA” or “in vitro transcription” refer to a process wherein RNA is synthesized in a cell-free system (in vitro). DNA, particularly plasmid DNA, is used as a template for the generation of RNA transcripts. RNA can be obtained by DNA-dependent in vitro transcription from an appropriate DNA template, which according to the present invention is preferably a linearized plasmid DNA template. The promoter for controlling the in vitro transcription can be any promoter from any DNA-dependent RNA polymerase. Particular examples of DNA-dependent RNA polymerases are T7, T3, and SP6 RNA polymerases. A DNA template for in vitro RNA transcription can be obtained by cloning a nucleic acid, in particular the cDNA corresponding to the respective RNA to be transcribed in vitro.and introducing it into an appropriate vector for in vitro transcription, for example, plasmid DNA. In a preferred embodiment of the present invention, the DNA template is linearized with a suitable restriction enzyme before being transcribed in vitro. The cDNA can be obtained by reverse transcription of mRNA or chemical synthesis. In addition, the DNA template for in vitro RNA synthesis can also be obtained by gene synthesis. Methods for in vitro transcription are known in the art (see, e.g., Geall i oou et al. (2013) Semin. Immunol. 25(2): 152-159; Brunelle et al. (2013) Methods Enzymol. 530:101-14 ). Reagents used in such a method typically include: 1) a linearized DNA template with a promoter sequence that has a high binding affinity for its respective RNA polymerase, such as the RNA polymerases encoded by bacteriophages; 2) ribonucleoside triphosphates (NTPs) for the four bases (adenine, cytosine, guanine, and uracil); 3) optionally, a CAP analogue as defined above (e.g., m7G(5')ppp(5')G (m7G)); 4) a DNA-dependent RNA polymerase capable of binding to the promoter sequence within the linearized DNA template (e.g., T7, T3, or SP6 RNA polymerase); 5) optionally, a ribonuclease (RNase) inhibitor to inactivate any contaminating RNase; 6) optionally, a pyrophosphatase to degrade pyrophosphate, which can inhibit transcription; 7) MgCI2, which provides Mg2+ ions as a polymerase cofactor; 8) a buffer to maintain a suitable pH value, which may also contain antioxidants (e.g. DTT) and / or polyamines such as spermidine in optimal concentrations. Full-length protein: The term “full-length protein,” as used herein, typically refers to a protein that comprises substantially the entire amino acid sequence of the naturally occurring protein. However, amino acid substitutions, for example, due to mutations in the protein, are also included within the term “full-length protein.” Protein fragments: “Fragments” of proteins or peptides in the context of the present invention may typically comprise a sequence of a protein or peptide as defined herein, i.e. with respect to its amino acid sequence (or its encoded nucleic acid molecule), N-terminally and / or C-terminally truncated compared to the amino acid sequence of the original (native) protein (or its encoded nucleic acid molecule). Such truncation may thus occur at the amino acid level or correspondingly at the nucleic acid level. Therefore, a sequence identity with respect to said fragment as defined herein may preferably refer to the complete protein or peptide as defined herein or to the complete (coding) nucleic acid molecule of such protein or peptide. 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. Thus, variant nucleic acids or genes may preferably comprise, in their nucleic acid sequence, at least one mutation, substitution, insertion, or deletion compared to their respective reference sequence. Preferably, the term “variant,” as used herein, includes naturally occurring variants and genetically modified variants of nucleic acid sequences or genes.Therefore, a “variant” as defined herein may be derived from, isolated from, related to, based on, or homologous to the reference nucleic acid sequence. Furthermore, the term “variant,” as used herein in the context of proteins or peptides, will be recognized and understood by one of ordinary skill in the art and is, for example, intended to refer to a protein or peptide variant having an amino acid sequence that differs from the original sequence by one or more mutations, such as one or more substituted, inserted, and / or deleted amino acids. Preferably, these fragments and / or variants have the same biological function or specific activity compared to the full-length native protein, for example, its specific antigenic property. “Variants” of proteins or peptides as defined herein may comprise conservative amino acid substitutions compared to their native, i.e., unmutated, physiological sequence.These amino acid sequences, as well as their coding nucleotide sequences in particular, fall under the term "variants" as defined herein. Substitutions in which amino acids originating from the same class are exchanged for each other are referred to as conservative substitutions. These include, in particular, amino acids with aliphatic side chains, positively or negatively charged side chains, aromatic groups on the side chains, or amino acids whose side chains can form hydrogen bonds, e.g., side chains with a hydroxyl function.This means that, for example, an amino acid having a polar side chain is replaced by another amino acid having an equally polar side chain, or, for example, an amino acid characterized by a hydrophobic side chain is replaced by another amino acid having an equally 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 positions in the sequence that do not cause any modification to the three-dimensional structure or that do not affect the binding region. Modifications of a three-dimensional structure by insertion(s) or deletion(s) can be easily determined, for example, by 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 said protein or peptide. Preferably, a variant of a protein comprises a functional variant of the protein, meaning 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 from which it is derived. Furthermore, the term “fragment” in the context of nucleic acid sequences or genes refers to a continuous subsequence of the full-length (or “parent”) reference gene or nucleic acid sequence. In other words, a “fragment” can typically be a shorter portion of a full-length gene or nucleic acid sequence. Accordingly, a fragment typically consists of a sequence that is identical to the corresponding stretch within the full-length gene or nucleic acid sequence. The term includes both naturally occurring fragments and 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 from which the fragment is derived, representing at least 20%, preferably at least 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 stated sequence identity with respect to such a fragment preferably relates to the complete 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 at least 70%, more preferably at least 80%, even more preferably at least 85%, even more preferably at least 90% and most preferably at least 95% or even 97%, to a reference nucleic acid sequence or gene from which it is derived. Furthermore, in this context, a fragment of a protein may typically comprise an amino 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 at least 80%, even more preferably at least 85%, even more preferably at least 90% and most preferably at least 95% or even 97%, with an amino acid sequence of the respective naturally occurring full-length protein. The term “identity,” as used herein in the context of a nucleic acid sequence or an amino acid sequence, will be recognized and understood by one of ordinary skill in the art and is intended, for example, to refer to the percentage at which two sequences are identical. To determine the percentage at which two sequences are identical, for example, nucleic acid sequences or amino acid (aa) sequences as defined herein, preferably the aa sequences encoded by the nucleic acid sequence as defined herein or the aa sequences themselves, the sequences may be aligned and subsequently compared to each other. Thus, for example, a position in a first sequence may be compared to a corresponding position in the second sequence.If a position in the first sequence is occupied by the same residue as a position in the second sequence, the two sequences are identical at this position. If this is not the case, the sequences differ at this position. If insertions occur in the second sequence compared to the first sequence, gaps may be inserted in the first sequence to allow for further alignment. If deletions occur in the second sequence compared to the first sequence, gaps may be inserted in the second sequence to allow for further alignment. The percentage where two sequences are identical is then a function of the number of identical positions divided by the total number of positions, including those positions occupied in only one sequence. The percentage where two sequences are identical can be determined using an algorithm, for example, an algorithm built into the BLAST program. Protein or peptide fragments in the context of the present invention may further comprise a sequence of a protein or peptide as defined herein, having a length of, for example, at least 5 amino acids, preferably a length of at least 6 amino acids, IVIA / a / ZUZZ / UU l oou preferably at least 7 amino acids, more preferably at least 8 amino acids, even more preferably preferably preferably preferably preferably preferably preferably at least at least 9 amino acids; even more preferably at least 10 amino acids; even more preferably at least 11 amino acids; even more preferably at least 12 amino acids; even more preferably at least 13 amino acids; even more preferably at least 14 amino acids; even more preferably at least 15 amino acids; even more preferably at least 16 amino acids; even more preferably at least 17 amino acids; even more preferably at least 18 amino acids; even more preferably at least 19 amino acids; even more preferably at least 20 amino acids; even more preferably at least 25 amino acids; even more preferably at least 30 amino acids; even more preferably at least 35 amino acids; even more preferably at least 50 amino acids; or most preferably at least 100 amino acids.For example, such a fragment may have a length of about 6 to about 20 or even more amino acids, for example, fragments processed and presented by MHC class I molecules, preferably having a length of about 8 to about 10 amino acids, for example, 8, 9, or 10 (or even 6, 7, 11 or 12 amino acids), or fragments processed and presented by MHC class II molecules, preferably having a length of about 13 or more amino acids, for example, 13, 14, 15, 16, 17, 18, 19, 20 or even more amino acids, these fragments being able to be selected from any part of the amino acid sequence. These fragments are typically recognized by T cells in the form of a complex consisting of the peptide fragment and an MHC molecule, i.e., the fragments are not normally recognized in their native form. The fragments of proteins or peptides may comprise at least one epitope of those proteins or peptides.Furthermore, domains of a protein, such as the extracellular domain, the intracellular domain, or the transmembrane domain, and shortened or truncated versions of a protein can also be understood to comprise a fragment of a protein. Protein variants: “Variants” of proteins or peptides, as defined in the context of the present invention, can be generated that have an amino acid sequence that differs from the original sequence by one or more mutations, such as one or more substituted mutations, 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, for example, its specific antigenic property. “Variants” of proteins or peptides as defined in the context of the present invention may comprise conservative amino acid substitutions compared to their native, i.e., non-mutated, physiological sequence. Such amino acid sequences, as well as their coding nucleotide sequences, in particular, fall under the term variants as defined herein.Substitutions in which amino acids from the same class are exchanged for each other are called conservative substitutions. These include amino acids with aliphatic side chains, positively or negatively charged side chains, aromatic groups in the side chains, or amino acids whose side chains can form hydrogen bonds, e.g., side chains with a hydroxyl function. This means, for example, that an amino acid with a polar side chain is replaced by another amino acid with an equally polar side chain, or that an amino acid characterized by a hydrophobic side chain is replaced by another amino acid with an equally 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 do not cause any modification to the three-dimensional structure or do not affect the junction region. Modifications to a three-dimensional structure by insertion(s) or deletion(s) can be readily determined, for example, by using CD spectra (circular dichroism spectra) (Urry, 1985, Absorption, circular dichroism and ORD of polypeptides, in: Modern Physical Methods in Biochemistry, Neuberger et al. (ed.), Elsevier, Amsterdam). 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 10, 20, 30, 50, 75 or 100 amino acids of such protein or peptide. Furthermore, protein or peptide variants as defined herein, which may be encoded by a nucleic acid molecule, may also comprise those sequences in which the nucleotides of the coding nucleic acid sequence are exchanged in accordance with the degeneracy of the genetic code, without leading to an alteration of the respective amino acid sequence of the protein or peptide, i.e. the amino acid sequence or at least part thereof may not differ from the original sequence by one or more mutations within the above meaning. Sequence identity: To determine the percentage at which two sequences are identical, for example, nucleic acid sequences or amino acid sequences as defined herein, preferably the amino acid sequences encoded by a nucleic acid sequence of the polymeric carrier as defined herein or the amino acid sequences themselves, the sequences can be aligned for subsequent comparison with each other. Thus, for example, a position in a first sequence can be compared with the corresponding position in the second sequence. If a position in the first sequence is occupied by the same component (residue) as is the case with a position in the second sequence, the two sequences are identical at this position. If this is not the case, the sequences differ at this position.If insertions occur in the second sequence compared to the first sequence, gaps can be inserted in the first sequence to allow for further alignment. If deletions occur in the second sequence compared to the first sequence, gaps can be inserted in the second sequence to allow for further alignment. The percentage where two sequences are identical is then a function of the number of identical positions divided by the total number of positions, including those positions that are only occupied in one sequence. The percentage where two sequences are identical can be determined using a mathematical algorithm. A preferred, but non-limiting, example of a mathematical algorithm that can be used is the algorithm of Karlin et al. (1993), PNAS USA, 90:5873-5877 or Altschul et al. (1997), Nucleic Acids Res., 25:3389-3402. Such an algorithm is integrated into the BLAST program.Sequences that are identical to the sequences of the present invention to some extent can be identified by this program. Derivative of a protein or peptide: A derivative of a peptide or protein is typically understood to be a molecule that is derived from another molecule, such as said peptide or protein. A “derivative” of IVIA / S / ZUZZ / UU / oou a peptide or protein also encompasses fusions comprising a peptide or protein used in the present invention. For example, the fusion comprises a tag, such as, for example, an epitope, for example, a FLAG epitope or a V5 epitope. For example, the epitope is a FLAG epitope. Such a tag is useful, for example, for purifying the fusion protein. Pharmaceutically effective amount: A pharmaceutically effective amount in the context of the invention is typically understood as an amount that is sufficient to induce an immune response. Carrier: A carrier in the context of the invention can typically be a compound that facilitates the transport and / or complexation of another compound. Said carrier can form a complex with said other compound. A polymeric carrier is a vehicle that is formed from a polymer. Carrier: An agent, for example, a vehicle that can typically be used within a pharmaceutical composition or vaccine to facilitate administration of the components of the pharmaceutical composition or vaccine to an individual. BRIEF DESCRIPTION OF THE DRAWINGS Figures 1A-11 (Chemical Structures of HEXA Lipids): shows the structures of the HEXA lipid compounds of the invention as described herein, i.e., lipid compound C1 (Figure 1A) HEXA-C4DE-PipSS, lipid compound C2 (Figure 1B) HEXA-C5DE-PipSS, lipid compound C3 (Figure 1C) HEXA-C6DE-PipSS, lipid compound C4 (Figure 1D) HEXA-C7DE-PipSS, lipid compound C5 (Figure 1E) HEXA-C8DE-PipSS, lipid compound C6 (Figure 1F) HEXACA-C3MEPipSS, lipid compound C7 (Figure 1G) HEXACA-C4ME-PipSS, lipid compound C8 (Figure 1H) HEXACA-C6ME-PipSS, lipid compound 09 (Figure 11) HEXACA-C8ME-PipSS (full details can be seen in example 2.1). Figures 2A-2E (Protonation / pKa profile of HEXA lipids) - shows the protonation / pKa profile of HEXA lipid compounds of the invention - Measurement of the degree of protonation through IblS fluorescence (2-p-toluidinylnaphthalene-6-sulfonate dye). A TNS fluorescence of LNP1, LNP2, LNP3 and LNP4 in composition 1 (DSPC). B TNS fluorescence of LNP5, LNP6, LNP7 in composition 1 (DSPC) and GN01. C TNS fluorescence of LNP8, LNP9, LNP10 and LNP11 in composition 21 (DPhyPEo4ME 16:0 PE). D TNS fluorescence of LNP12, LNP13, LNP14 in composition 2 (DPhyPE) and GN01. E TNS Fluorescence of LNP15 (in composition 1-DSPC), LNP16 (in composition 2-DPhyPE), LNP17 (in composition 2-DSPC), LNP 18 (in composition 2-DPhyPE) and GN01 (full details can be seen in Example 2.1.2 / Table Ex-4). Figures 3A-3C (HEAD Lipid Structures): shows the structures of the HEAD lipid compounds of the invention as described herein (full details can be seen in Example 2.1 / Table Ex-6), i.e., CISE lipid compound (Figure 3A), CPZE lipid compound (Figure 3B), ESTER lipid compound (Figure 3C). Figures 4A-4C (Protonation / pKa profile of HEAD lipids) - shows the protonation / pKa profile of the HEAD lipid compounds of the invention - Measurement of the degree of protonation by TNS fluorescence (2-p-toluidinylnaphthalene-6-sulfonate dye). Figure 4A TNS fluorescence of HEAD lipid CISE in composition A (DSPC) and composition B (DPhyPE) compared to GN01 Figure 4B TNS Fluorescence of HEAD lipid CPZE in composition A (DSPC) and composition B (DPhyPE) compared to GN01. Figure 4C TNS Fluorescence of HEAD lipid ESTER in composition A (DSPC) and composition B (DPhyPE) compared to GN01 (full details can be seen in Example 2.2.2 / Table Ex-9). Figure 5A-5D (PpLuc expression in HeLa and HepG2-HEXA lipids 1 to 7)-HEXA lipids 1 to 7 were formulated as LNPs using composition 1 or 2 and transfected with PpLuc mRNA into HeLa cells or HepG2 cells. The relative light unit (RLU) was measured 24 h post-transfection. Figure 5A Transfection of LNP1 to LNP7 (composition 1-DSPC) and GN01 in HeLa cells. Figure 5B Transfection of LNP8 to LNP14 (composition 2- DPhyPE) and GN01 in HeLa cells. Figure 5C Transfection of LNPI to LNP7 (composition 1-DSPC) and GN01 in HepG2 cells. Figure 5D Transfection of LNP8 to LNP14 (composition 2- DPhyPE) and GN01 in HepG2 cells, i.e., showing that the mRNA formulated with the lipids and compositions showed very good and even higher PpLuc expression in HeLa and in mice (full details can be seen in Example 3.1.1). Figure 6 (PpLuc expression in HeLa from HEAD lipids) - shows that compositions comprising DPhyPE again gave a clear advantage over DSPC which to date is used in the art as the standard neutral lipid in almost all state-of-the-art LNP compositions, according to Example 3.1.1 and Figures 5A-5D - HEAD lipids CISE, CPZE and ESTER were formulated as LNPs using composition A or B and transfected with PpLuc mRNA into HeLa cells. The relative light unit (RLU) was measured 24 h post-transfection (full details can be seen in Example 3.2.1). Figure 7 (hEPO expression of HEXA lipids 1 to 7 in HeLa cells) - shows good in vitro hEpo expression in HeLa cells after treatment - GN01 and HEXA lipids prepared as LNPs using composition 2 - DPhyPE was formulated with mRNA encoding hEPO and transfected into HeLa cells. hEpo ELISA was performed 24 h post transfection and shows transfection efficiency (full details can be seen in Example 4.1.1). Figure 8 (hEPO expression of HEXA lipids 1 to 7 in mice) - shows that also in vivo analysis of the compositions of the invention gave distinct high hEpo expression at 6 and 24 hours post-injection - GN01 and HEXA lipids were prepared as LNPs using composition 2 - DPhyPEs containing mRNA encoding hEPO were formulated and injected at 0.5 mg / kg into Balb / C mice (5 per group). HsEpo level was measured 6 h and 24 h post-injection in plasma using ELISA. (Full details can be seen in Example 4.1.1). Figures 9A-9B (HEXA lipid tolerability-liver enzymes)-shows that none of the tested animals showed significantly elevated AST and ALT liver enzyme activities compared to buffer control: For HEXA lipid tolerability analysis, ALT and AST levels were measured 24 h after intravenous transfection of the respective LNPs in Balb / C mice. A ALT and AST levels of LNP and GN01 containing HEXA lipids 1 to 9 compared to buffer. B ALT and AST levels of lipid m / m ratios 2 (m / m 20, m / m 30, m / m 40) and GN01 compared to buffer (full details can be seen in Example 4.1.2). Figures 10A-10H (Tolerability of HEXA lipid immunostimulation) - showing that none of the tested lipid compounds induced significantly elevated cytokine levels - for analysis of the immunostimulatory properties of HEXA lipids a CBA assay with serum samples taken from mice 6 h after injection of HEXA lipid-containing LNP and GN01 LNP was performed in Balb / C mice. IFN-α levels in the serum were determined by ELISA. Figure 10A MCP-1 from HEXA lipids 1 to 7 and GN01. Figure 10B IL-6 from HEXA lipids 1 to 7 and GN01. Figure 10C MP1-B from HEXA lipids 1 to 7 and GN01. Figure 10D IFN-α from HEXA lipids 1 to 7 and GN01. Figure 10E MCP-1 from HEXA lipids 8, 9 and lipid 2 m / m ratios (m / m 20, m / m 30, m / m 40) and GN01. Figure 10F IL-6 from HEXA lipids 8, 9 and lipid 2 m / m ratios (m / m 20, m / m 30, m / m 40) and GN01. Figure 10G MP1-B from HEXA lipids 8, 9 and lipid 2 m / m ratios (m / m 20, m / m 30, m / m 40) and GN01.Figure 10H INF-α of HEXA lipids8, 9 and Lipid 2 m / m ratios (m / m 20, m / m 30, m / m 40) and GN01 (full details can be seen in Example 4.1.2). Figures 11A-11D. (LNP for prophylactic and therapeutic vaccine approach - id injection of tumor antigen Trp2) - shows that vaccination (full details can be seen in Example 4.2.1) using GN01, GN02 and CISE LNP comprising trp2 mRNA showed stable IgG1 and IgG2 titers (Figure 11A and 11B) and that GNOI, GN02 and CISE LNP showed low T cell responses (Figure 11C and 11D), i.e. C57 / BL6 mice were injected intradermally (id) in the back with formulated mRNA encoding tumor antigen Trp2 and either GN01, GN02 or CISE. Immunization took place on day 0, day 7, and day 14. Blood samples were taken at 14 h and blood and organ samples were taken 21 days after the first vaccination. T-cell responses and humoral immune responses were measured by ELISA. A IgG1 endpoint titer. B IgG2a[b] CD4+ cell endpoint titer. C% TNFα+ / IFNγ+. Figure 12.1 (HEADs Lipid Tolerability-Liver Enzymes) - shows that none of the tested animals showed significantly elevated AST and ALT liver enzyme activities compared to the buffer control; for the analysis of HEAD lipid tolerability, ALT and AST levels were measured 24 h after intravenous transduction in Balb / C mice. ALT and AST levels of HEAD lipids ESTER (m / m 40) and CPZE (m / m 20) were measured and compared to the levels of CISE / lipid 2 (m / m 30), lipid 2 (m / m 30), and GN01 and buffer. Different molar / mass ratios (m / m) were used (m / m 20, m / m 30, m / m 40) (full details can be seen in Example 4.2.2). Figures 12.2A-12.2D (Tolerability of HEAD lipids - immunostimulation) - show that none of the tested lipid compounds induced significantly elevated cytokine levels - for analysis of the immunostimulatory properties of HEAD lipids (CPZE, ESTER) compared to HEXA lipids (Lipid 2), GN01 and a mixture of both (CISE / Lipid 2) a CBA assay was performed using serum samples taken from mice 6 h after injection of HEXA lipids into Balb / C mice. IFN-α levels in the serum were determined by ELISA. A MCP-1. B IL-6. C MP1-B. D INF-α (full details can be seen in Example 4.2.2). Figures 13A-13B (stability of the LNPs of the invention after prolonged storage): shows the analysis of the integrity and biophysical properties of the GN01 LNPs that were ML / a / ZUZZ / UU l oou were stored at 4°C and -80°C for an extended period of time. As evident, the particles and RNA were stable and no significant differences were observed, i.e., changes in the biophysical properties and mRNA integrity of the LNPs could be shown in agarose gels after gel electrophoresis. GN01 LNPs were formulated with hEPO mRNA and stored at 4°C and -80°C for 1.5 or 6 months. For gel electrophoresis analysis, the LNPs were disrupted so that the incorporated mRNA could be displayed in the gel. After 1.5 months (Figure 13A), 6 months (Figure 13B) - decomposition condition 1 (a combination of heparin and triton was used to decompose the LNPs; C1 in the figure), decomposition condition 2 (a combination of heparin and Pluronic® and heating at 45°C for 15 min was used to decompose the LNPs; C2 in the figure) (full details can be seen in example 5.1). Figure 14.1 (Biological activity of GNOI after storage at -80 °C for 10 weeks): shows the analysis of GN01-formulated mRNA after 10 weeks of storage, which resulted in an even higher expression efficiency after 6 h and 24 h post-injection compared to 1 week of storage, i.e., the biological activity of the formulated GN01 was assessed by ELISA. GN01 LNPs were formulated with hEPO mRNA and frozen for 1 week and 10 weeks, respectively. Balb / C mice (5 mice / group) were injected intravenously. Plasma samples were taken and analyzed 6 h and 24 h post-injection (full details can be seen in Example 5.2). Figures 14.2A-14.2B (Biological activity of GNOI LNPs after different F / T cycles): shows a second evaluation where plasma samples were analyzed after one freeze / thaw cycle (1 F / T) compared to plasma samples after 2 F / T cycles (both after 1 week of storage at -80°C) - the results were that the biological activity of hsEpo could be shown for all tested approaches - i.e. the biological activity of the formulated GN01 was assessed by ELISA. GN01 LNPs were formulated with hEPO mRNA and frozen for 1 week and injected intravenously into Balb / C mice (5 mice / group). Plasma ELISA levels were analyzed after 1 F / T cycle (Figure 14.2A) and 2 F / T cycles (Figure 14.2B) (full details can be seen in Example 5.2). Figure 15.1A and 15.1B (Phospholipid component variations and influence on invention compositions) - shows that incorporation of DPhyPE resulted in increased expression compared to the standard neutral lipid DSPC - i.e., LNPs were generated using different phospholipids (DPhyPE, DSPC, DPhyPE+DSPC (1+1)). Lipid 1 (lipid compound C1) and LNP GN01 were formulated into PpLuc mRNA and transfected into HeLa cells. Transfection efficiency was analyzed 24 h post-transfection by measuring RLU intensity. B Measurement of the degree of protonation via TNS fluorescence (2-p-toluidinylnaphthalene-6-sulfonate dye) of GN01 and LNP comprising lipid compound C1 comprising different phospholipids dotted line = GN01; dashed line = DPhyPE; normal line = DSPC, step-like line to the right of the dashed line with = DSPC / DPhyPE (full details can be seen in Example 6). Figure 15.2 (PEG component variations and influence on the compositions of the invention) - shows that compositions comprising lipids conjugated with polymers with chains MA / a / ¿U¿¿ / UU l shorter alkyl chains (O8,C8-ceramide-PEG tails, indicated in the figure as Cer8) were more efficient than compositions comprising lipids conjugated to polymers comprising longer alkyl chains (C14 = C14 DMG-PEG = 1,2-dimyristoyl-rac-glycero-3-methoxypolyethyleneglycol2000 (DMG-PEG 2000)) = expression of PpLuc in HepG2 cells - filled bars show results after 1 h, open bars show results after 4 h (full details can be seen in Example 7). Figure 16 (GN01 anti-rabies mAb expression after a single iv injection) - shows the expression of an anti-rabies monoclonal antibody formulated in GN01 LNP after a single iv injection - as is evident, a very strong anti-rabies mAb expression could be detected after an iv injection after 6 hours and 24h (full details can be seen in Example 8). Figures 17A-17D (Immunogenicity of GN01 and GN02 in v / v / o - T cell response - VNT analysis) - Figure 17A shows that already a single im immunization with 5 pg of RABV-G mRNA formulated with GN01 and GN02-LNP induced very robust VNTs well above the protective titer of 0.5 IU / mI in all animals at day 35 after the first vaccination. Figures 17B and 17C show that the inventive RABV-G mRNA vaccine formulated with GN01 and GN02-LNP induced specific cellular responses after vaccination, effects that were not observed in control animals vaccinated with LNP. RABV-G-specific CD4+ T cells (Figures 17B) were observed for both GN01 and GN02 mRNA formulations. This was also true for RABV-G-specific CD8+ T cells (Figures 17C) (full details can be seen in Example 9). Figures 18A-18D (GN01 for monotopic vaccine approach)—show that high reactogenicity of the GN01-formulated RNA could be observed; splenocyte numbers are increased by vaccination with monotopic constructs containing PADRE via GN01 LNP (Figure 18A). The monotopic constructs, in combination with the GN01 formulation and intradermal application, resulted in very potent CD8 T cell responses (Figure 18B, 18C, and 18D) (full details can be seen in Example 10). Figure 19 (GN01 for influenza / flu-H3N2 vaccination) - shows that a single im immunization with 10 pg HA mRNA formulated with GN01 LNP induced a protective HI titer well above the protective titer of 40 in all animals at day 21 post initial vaccination and boosting with 10 pg HA mRNA formulated with GN01 LNP induced a manifold increase in the humoral immune response (full details can be seen in Example 11). Figure 20 (GN01 for Rabies tested in calf animal model) - shows that intramuscular vaccination of calves with mRNA encoding RABV-G formulated with GN01 led to a very strong induction of neutralizing antibodies already after primary vaccination after 14 days and already with a dose of only 30 pg mRNA (QMS standard of 0.5 IU / ml is indicated by a dashed line; open bars = rabisin control, closed bars = mRNA formulated with GN01) (full details can be seen in Example 12). Figures 21.1A-21.1B (GN01 for in v / vo malaria vaccination - Final end-point titers) show that the mRNA malaria vaccine formulated with GN01 encoding CSP induced very strong humoral immune responses in mice, using an ELISA assay (Figure 21.1 A - overlay: peptide ινΐΛ / a / zuzz / uu / oou [NANP]7, IgG1 and IgG2a endpoint titers at day 21 and day 35 post-priming; Figure 21.1B: C-terminal cap peptide, IgG1 and IgG2a endpoint titers at day 21 and day 35 post-priming; Group 1: GN01-LNP with CSP vaccine; Group 2: GN01-LNP with relevant mRNA (full details can be seen in Example 13). Figure 21.2 (GN01 for in v / vo-ICS malaria vaccination) shows that GN01 formulated an mRNA malaria vaccine encoding CSP-induced cellular immune responses in mice (CD8+ and / or CD4+ T cell responses), using an intracellular cytokine staining assay (day 35 post-vaccination). Groups 1: GN01-LNP with CSP vaccine; Group 2: GN01-LNP with irrelevant mRNA (full details can be seen in Example 13). Figure 22 (GN01 for in vivo expression of FGF21) shows that FGF21 mRNA formulated in the LNPs of the invention resulted in high concentrations of FGF21 after administering a low dose of 0.25 mg / kg in mice by iv injection (full details can be seen in Example 14). Figure 23 (GN01 for in vivo expression of FGF21) shows that FGF21 mRNA formulated into the inventive LNPs resulted in very high concentrations of FGF21 after administering a high dose of 1 mg / kg into mice by iv injection (full details can be seen in Example 14). Figures 24A-24B (Chemical structures of HEXA lipids) - show the structures of the HEXA lipid compounds of the invention as described herein, i.e., the inverted HEXA-C5DE-PipSS lipid compound C24 (Figure 24A) and the inverted HEXA-C5DE-Pip-C3 thioether lipid compound C25 (Figure 24B) (full details can be seen in Example 20.1). Figures 25A-25B (HEAD Lipid Structures) - show the structures of the HEAD lipid compounds of the invention as described herein (full details can be seen in Example 20.2), i.e., the lipid compound THIOETHER (Figure 25A) and the lipid compound C3SS (Figure 25B). Figure 26 (Immunogenicity of LNPs comprising C2 in in vivo T cell response VNT assay): The figure shows that a single im immunization with 5 pg of LNP (comprising C2) formulated with RABV-G-mRNA induced very robust VNTs well above the protective titer of 0.5 IU / ml in all animals at day 21 after the first vaccination. Full details can be found in Example 21. Figures 27A-27C (Immunogenicity of different LNPs comprising cationic lipids in VNT analysis of in vivo T cell response) - Figure 27A shows that already a single immunization with 5 pg of RABV-G mRNA formulated with LNPs induced very robust VNTs well above the protective titer of 0.5 IU / ml in all animals on day 21 after the first vaccination. LNPs were formulated with different cationic lipids according to the invention as indicated in Example 21. Figures 27B and 27C show that the RABV-G mRNA vaccine formulated with LNPs of the invention induced specific cellular responses after vaccination in restimulated splenocytes versus unstimulated splenocytes. RABV-G-specific CD4+ T cells (Figures 27B) and RABV-G-specific CD8+ T cells (Figures 27C) are shown for the (a) restimulated and (b) unstimulated configuration. Full details can be found in Example 21. Figure 28 (Immunogenicity of LNPs comprising THIOETER in in vivo VNT analysis of T cell responses): The figure shows that already a single im immunization with 1 pg of LNP (comprising thioether) formulated with RABV-G-mRNA induced very robust VNTs well above the protective titer of 0.5 IU / ml in all animals on day 21 after the first vaccination. Full details can be found in Example 21. Figure 29 (GN02-like LNPs for in v / vo-ICS malaria vaccination) shows that the formulated GN02-like mRNA malaria vaccine encodes CSP-induced cellular immune responses in mice (CD4+ T cell responses), using an intracellular cytokine staining assay (day 35 post-vaccination). RABV-G-specific CD4+ T cells are shown for the (a) re-stimulated and (b) unstimulated configuration. Full details can be found in Example 22. Figure 30 (GN02-like LNPs for in v / vo-ICS malaria vaccination) shows that the formulated GN02-like mRNA malaria vaccine encodes CSP-induced cellular immune responses in mice (CD8+ T cell responses), using an intracellular cytokine staining assay (day 35 post-vaccination). RABV-G-specific CD8+ T cells are shown for the (a) re-stimulated and (b) unstimulated configuration. Full details can be found in Example 22. Figure 31 (GN02-like LNPs for in v / vo malaria vaccination - total IgG titer): shows that the formulated GN02-like mRNA malaria vaccine encoding CSP induced very strong humoral immune responses in mice, using an ELISA assay (coating: peptide [NANP]7, endpoint total IgG titers at day 35 post-priming (full details can be found in Example 22). Figure 32 (LNPs with different cationic lipids of the invention for in vivo-CS malaria vaccination) shows that the LNP-formulated mRNA malaria vaccine encodes CSP-induced cellular immune responses in mice (CD4+ T cell responses shown for (a) restimulated and (b) unstimulated configuration), using an intracellular cytokine staining assay (day 35 post-vaccination). Full details can be found in Example 22. Figure 33 (LNPs with different cationic lipids of the invention for in v / vo-ICS malaria vaccination) shows that the LNP-formulated mRNA malaria vaccine encodes CSP-induced cellular immune responses in mice (CD8+ T cell responses shown for (a) restimulated and (b) unstimulated configuration), using an intracellular cytokine staining assay (day 35 post-vaccination). Full details can be found in Example 22. Figure 34 (LNP with different cationic lipids of the invention for in v / vo malaria vaccination - total IgG titer) - shows that the mRNA malaria vaccine formulated with LNP encoding CSP induced very strong humoral immune responses in mice, using an ELISA assay (coating: [NANP]7 peptide, Total IgG endpoint titers at day 35 post-priming (full details can be found in Example 22). Figure 35 (LNP with the C26 lipid of the invention for in vivo malaria vaccination IgG1 titer) - shows that the mRNA malaria vaccine formulated with LNP encoding CSP induced very strong humoral immune responses in mice, using an ELISA assay (coating: [NANP]7 peptide, IgG1 endpoint titers at day 35 post-priming (full details can be found in Example 22). DETAILED DESCRIPTION OF THE INVENTION The present invention is based on the inventors' surprising discovery that the use of novel cationic lipids and / or lipid nanoparticles (LNPs) is highly effective for delivering nucleic acids such as mRNA to a living organism such as a human individual. In particular, the intracellular delivery of such nucleic acids is enhanced. This has allowed the inventors to create, for example, improved vaccines that deliver mRNA compounds encoding antigenic peptides or proteins and very effectively induce antigen-specific immune responses at very low doses. Other advantages achieved by the present invention are that, surprisingly, the inventors have discovered, in accordance with aspects and embodiments of the invention, a class of formulations for delivering mRNA vaccines in vivo that results in a significantly improved and, in many respects, synergistic approach.immune responses, including enhanced antigen generation and the production of functional antibodies with neutralizing capacity. These results can be achieved even when administering significantly lower doses of mRNA compared to the mRNA doses used in other classes of lipid-based formulations. The formulations of the invention have demonstrated significant and unexpected in vitro immune responses sufficient to establish the efficacy of the functional mRNA vaccines as prophylactic and therapeutic agents. Typically, self-replicating RNA vaccines rely on viral replication pathways to deliver sufficient RNA into a cell to produce an immunogenic response; the formulations of the present invention do not require viral replication to produce sufficient protein to result in a strong immune response.Thus, preferably, the mRNA of the invention is not self-replicating RNA and does not include components necessary for viral replication. Lipid compositions In a first aspect, the invention relates to a composition comprising a cationic lipid as described hereinbelow. All options and preferences described for the cationic lipid as such are also applicable to the composition of this aspect of the invention. In other words, the specifically described embodiments of cationic lipids, and in particular the preferred cationic lipids, should be understood as also defining specific preferred embodiments of the composition according to the invention, i.e., compositions characterized in that they comprise a cationic lipid according to one of the specific selections described herein. The composition may comprise other active and / or inactive excipients described below.In a specific embodiment, in addition to the cationic lipid, the composition comprises one or more lipids selected from the group consisting of: (a) a steroid; (b) a neutral lipid; and (c) a polymer-conjugated lipid. preferably a pegylated lipid. ac / ]Cationic lioids The cationic lipid is preferably cationizable, i.e., it becomes protonated as the pH decreases below the pKa of the ionizable group of the lipid, but becomes progressively more neutral at higher pH values. When positively charged, the lipid can associate with negatively charged nucleic acids. In certain embodiments, the cationic lipid comprises a zwitterionic lipid that assumes a positive charge as the pH decreases. In one aspect, the invention provides a novel cationic lipid which is defined as a compound according to formula (I): Ra-A-Rbformula (I) where is Rase selects from: O . ,r' VNiRY ° , or -R1-N(H)-C(O)-R3-R4; Rbse is selected from: r' YNI k 4RY or -R1-N(H)-C(O)-R3-R4, or -R1-N(CH3)2; A is -S-, -SS-, -NH-C(O)-, -NH-C(O)O-, -NH-C(O)-NH-, -SC(O)-N(H)-, -C(O)O-, or -OP(O)(OH)-O-; R1 is an optionally substituted linear or unbranched ethanedyl, propanedyl, butanedyl, or alkanedyl having 2 to 8 carbon atoms; R2 is an alkanedyl having 2 to 8 carbon atoms; R3 is optional, and if present, is -R5-C(O)-O-, -R5-OC(O)-, -R5-C(O)-NH-, -R5OC(O)-NH-, or R5-NH-C(O)O-; R4 is a lipophilic substituent with 12 to 36 carbon atoms; R5 is an alkanedyl having 1 to 6 carbon atoms; X is a carbon or nitrogen atom; where all selections are independent of each other, optionally provided that if R1, R2, and R5 are all unsubstituted linear ethanedyl, A is -SS-, and Ray Rb are identical, then R4 is not IVIA / a / ZUZZ / UU l oou In another aspect, the present invention relates to novel cationic lipids that are useful for the delivery of nucleic acids into living cells. The cationic lipids are compounds according to formula (I): Ra-A-Rbformula (I) where Rase selects from: °0, or -R1-N(H)-C(O)-R3-R4; Rbse is selected from: oo -R1-N(H)-C(O)-R3-R4, or -R1-N(CH3)2; A is -S-, -SS-, -SC(O)- -NH-C(O)-, -NH-C(O)O-, -NH-C(O)-NH-, -SC(O)N(H)-, -C(O)O-, or -OP(O)(OH)-O-; R1 is an optionally substituted linear or unbranched ethanedyl, propanedyl, butanedyl, or alkanedyl having 2 to 8 carbon atoms; R2 is an alkanedyl having 2 to 8 carbon atoms; R3 is optional, and if present, is -R5-C(O)-O-, or -R5-OC(O)-, -R5-C(O)-NH, -R5-OC(O)-NH-, or R5-NH-C(O)O-; R4 is a lipophilic substituent with 12 to 36 carbon atoms; R5 is an alkanedyl having 1 to 6 carbon atoms; X is a carbon or nitrogen atom; where all selections are independent of each other, optionally provided that if R1, R2, and R5 are all ethanedyl, A is -SS-, and Rb are identical, then R4 is not l oou In yet another aspect, aspect A, the invention provides a novel cationic lipid which is defined as a compound according to formula (I): Ra-A-Rbformula (I) or a pharmaceutically acceptable salt, prodrug or stereoisomer thereof, wherein Rase selects from: R R R , or -R1-N(H)-C(O)-R3-R4; Rbse is selected from: -R1-N(H)-C(O)-R3-R4, or -R1-N(CH3)2; A is -S-, -SS-, -NH-C(O)-, -NH-C(O)O-, -NH-C(O)-NH-, -SC(O)-N(H)-, -C(O)O-, or -OP(O)(OH)-O-; R1 is a linear or unbranched ethanedyl, propanedyl, butanedyl, or alkanedyl having 2 to 8 carbon atoms, wherein each substitutable carbon atom is unsubstituted or substituted with one or more C1-C4 alkyl, C1-C4 alkenylene, Cs-Cs cycloalkylene, or Cs-Cs cycloalkenylene; R2 is an alkanedyl having 2 to 8 carbon atoms; R3 is optional, and if present, is -R5-C(O)-O-, -R5-OC(O)-, -R5-C(O)-NH-, -R5OC(O)-NH-, or R5-NH-C(O)O-; R4 is a lipophilic substituent with 12 to 36 carbon atoms, wherein the lipophilic substituent with 12 to 36 carbon atoms is either a linear or branched alkyl or alkenyl having 12 to 25 carbon atoms or derived from alpha-tocopherol; R5 is an alkanedyl having 1 to 6 carbon atoms; X is a carbon atom bonded to a hydrogen atom (CH) or a nitrogen atom; where all selections are independent of each other; optionally provided that if (i) R3 is present as -R5-C(O)-O-, (ii) R1 and R2 are unsubstituted linear ethanedyl, (iii) R5 is either unsubstituted linear ethanedyl, unsubstituted linear propanedyl or unsubstituted linear butanedyl, (iv) A is -SS-, and (v) Ray Rb are identical, then R4 is not and furthermore whenever (i) R3 is absent, (i) R1 and R2 are unsubstituted linear ethanedyl, (iii) A is -SS-, and (iv) Ray Rb are identical, so R4 is not and not ; or, as an alternative to the above provision, optionally provided that the cationic lipid is not a lipid selected from the group consisting of In the novel cationic lipid, the degradable / biodegradable moiety A connects the two structures Ra and Rb, which may be the same or different. Each of Ray and Rb includes at least one basic, i.e., cationic, moiety including a tertiary nitrogen atom. At least one of Ray and Rb has a substantially lipophilic tail structure and at least one ester group. The degradable / biodegradable moiety A may be selected from the following functional groups: -S-, -SS-, -NH-C(O)-, -NH-C(O)O-, -NH-C(O) )-NH-, -SC(O)-N(H)-, -C(O)O-, or -OP(O)(OH)-O- In one preferred embodiment, A is a moiety or group containing one or more sulfur atoms, such as -S-, -SS-, or -SC(O)-N(H)-. In another preferred embodiment, A is a disulfide group (SS-), wherein the cationic lipid may be represented as Ra-SS-Rb, wherein Ra and Rb may be selected as defined above. In yet another preferred embodiment, in particular of aspect A above, A is -S-, wherein the cationic lipid may be represented as Ra-S-Rb, wherein Ra and Rb may be selected as defined above. Without wishing to be bound by theory, the inventors currently believe that the degradability of the A moiety may play a key role in the pronounced biological efficacy of the novel lipids. For example, if A is a disulfide moiety, and if the lipids are used in conjunction with other excipients as described in more detail below to form a liposome or lipid nanoparticle (LNP) loaded with a nucleic acid compound as cargo, such a liposome or LNP would be effectively taken up by a cell via endocytosis. Within an endocytic vesicle, the disulfide group of the cationic lipid can be reduced (possibly in the presence of glutathione) into two thiol moieties, which at the same time leads to the cleavage of the cationic lipid molecule into two smaller cationic species. Potentially, Since Ra and Rb can optionally be different from each other, they can be selected independently. As mentioned, Ra can be selected from ν η Yr ηRYR RYR O , or , preferably with X being CH, or -R1-N(H)-C(O)-R3-R4; and Rb may be selected from R' XX And n , l / V 4RYR0, preferably with X being CH, -R1-N(H)-C(O)-R3-R4, or -R1-N(CH3)2. Furthermore, as mentioned, Ra can be selected from ooo IVIA / a / ZUZZ / UU / oou Or, preferably with X being CH, and Rb can be selected from ° o0, preferably with X being CH. In one preferred embodiment, at least one of R and R comprises a piperidine- or piperazine-derived six-membered ring structure between R and A or R, respectively. This means that at least one tertiary nitrogen atom that is present and located near the A or R moiety is separated from the lipophilic tail structure R by at least one spacer (R) of any ester group. A potential advantage of the ester group (or groups, if R is present) relates to the increased degradability of the lipid in a physiological environment, e.g., in an intracellular environment, which is provided by the hydrolytically labile ester bonds. In yet another embodiment, both Ra and Rb comprise a six-membered ring structure derived from piperidine or piperazine. Also preferred is a cationic lipid wherein both Ra and Rb are r' YNi or ύνγ'ν0, preferably with X being CH, either independently selected or alternatively Ra and Rb being identical. As mentioned, R1 is an optionally substituted linear or unbranched ethanedyl, propanedyl, butanedyl, or alkanedyl having 2 to 8 carbon atoms. Propanediyl is preferably n-propanediyl, i.e. -CH2-CH2-CH2- wherein one or more hydrogen atoms are optionally substituted. Butanediyl is preferably n-butanedyl, i.e. -CH2-CH2-CH2-CH2- wherein one or more hydrogen atoms are optionally substituted. Preferably, however, no more than one hydrogen atom of the ethanedyl, propanediyl, or butanediyl is substituted. In some embodiments, the R1 substituent on Ra and the R1 substituent on Rb are the same or different. In some embodiments, the R1 substituent on Ra and the R1 substituent on Rb are both ethanedyl. In other embodiments, the R1 substituent on Ra and the R1 substituent on Rb are both propanediyl. In other embodiments, the R1 substituent on Ra and the R1 substituent on Rb are both butanediyl.In some embodiments, the R1 substituent on Ra is ethanediyl and the R1 substituent on Rb is propanediyl. In other embodiments, the R1 substituent on Ra is propanediyl and the R1 substituent on Rb is ethanedyl. In some embodiments, the R1 substituent on Ra is butanediyl and the R1 substituent on Rb is propanediyl. In other embodiments, the R1 substituent on Ra is butanediyl and the R1 substituent on Rb is ethanedyl. In certain other embodiments, particularly when it comes to R1, the term optionally substituted indicates that each substitutable carbon atom can be independently substituted with one or more C1-C4 alkyl, C1-C4 alkenylene, C3-C8 cycloalkylene, or C3-C8 cycloalkenylene. the R1 substituent on Ra is ethanediyl and the R1 substituent on Rb is propanediyl. In other embodiments, the R1 substituent on Ra is propanediyl and the R1 substituent on Rb is ethanediyl. In some embodiments, the R1 substituent on Ra is butanediyl and the R1 substituent on Rb is propanediyl.In other embodiments, the R1 substituent on Ra is butanediyl and the R1 substituent on Rb is ethanedyl. In certain other embodiments, particularly where R1 is concerned, the term “optionally substituted” indicates that each substitutable carbon atom may be independently substituted with one or more C1-C4 alkyl, C1-C4 alkenylene, C3-C8 cycloalkylene, or C3-C8 cycloalkenylene. The R1 substituent on Ra is ethanediyl and the R1 substituent on Rb is propanediyl. In other embodiments, the R1 substituent on Ra is propanediyl and the R1 substituent on Rb is ethanedyl. In some embodiments, the R1 substituent on Ra is butanediyl and the R1 substituent on Rb is propanediyl. In other embodiments, the R1 substituent on Ra is butanediyl and the R1 substituent on Rb is ethanedyl.In certain other embodiments, particularly where R1 is concerned, the term "optionally substituted" means that each substitutable carbon atom may be independently substituted with one or more C1-C4 alkyl, C1-C4 alkenylene, C3-C8 cycloalkylene, or C3-C8 cycloalkenylene. The R1 substituent on Rb is butanediyl and the R1 substituent on Rb is propanediyl. In other embodiments, the R1 substituent on Rb is butanediyl and the R1 substituent on Rb is ethanedyl. In certain other embodiments, particularly where R1 is concerned, the term "optionally substituted" means that each substitutable carbon atom may be independently substituted with one or more C1-C4 alkyl, C1-C4 alkenylene, C3-C8 cycloalkylene, or C3-C8 cycloalkenylene. the R1 substituent on Ra is butanediyl and the R1 substituent on Rb is propanediyl. In other embodiments, the R1 substituent on Ra is butanediyl and the R1 substituent on Rb is ethanedyl.In certain other embodiments, particularly when it comes to R1, the term optionally substituted indicates that each substitutable carbon atom can be independently substituted with one or more C1-C4 alkyl, C1-C4 alkenylene, C3-C8 cycloalkylene, or C3-C8 cycloalkenylene. Similarly, in some embodiments, the R2 substituent on Ra and the R2 substituent on Rb are the same or different. In some embodiments, the R2 substituent on Ra and the R2 substituent on Rb are ethanediyl, propanediyl, butanediyl, pentanediyl, hexanediyl, heptanediyl, or octanediyl. In other embodiments, the R2 substituent on Ra is propanediyl and the R2 substituent on Rb is heptanediyl. In other embodiments, the R2 substituent on Ra is heptanediyl and the R2 substituent on Rb is propanediyl. In some embodiments, in particular of aspect A above, the R2 substituent on Ra and the R2 substituent on Rb are both ethanediyl. Furthermore, in some embodiments where R3 is present on both Ra and Rb, the R5 substituent on Ra and the R5 substituent on Rb are the same or different. In some embodiments, the R5 substituent on Ra and the R5 substituent on Rb are methanediyl, ethanediyl, propanediyl, butanediyl, pentanediyl, or hexanediyl. In other embodiments, the R5 substituent on Ra is ethanediyl and the R5 substituent on Rb is hexanediyl. In other embodiments, the R5 substituent on Ra is hexanediyl and the R5 substituent on Rb is ethanedyl. In some embodiments, in particular of aspect A above, where R3 is present on both Ra and Rb, the R5 substituent on Ra and the R5 substituent on Rb are both ethanedyl. The substituent may be any suitable substituent, i.e. any linear or branched alkyl, aryl, heteroalkyl, heteroaromatic structure which may optionally include other functional groups such as ester or amide groups. In particular, if -R1-N(H)-C(O)-R3-R4 is selected for Ray and / or Rb, it is preferred that R1 is a linear or unbranched ethanedyl, propanediyl, butanediyl, or alkanedyl having from 2 to 8 carbon atoms, such as a substituted propanediyl. In the case where an -R1-N(H)-C(O)-R3-R4 is used which does not include a cationic moiety such as an amino group, it is preferred that the substituent of R1 comprises said amino group; optionally, said amino group may form part of a cyclic structure, such as a six-membered ring structure derived from piperidine or piperazine. Optionally, the ring structure has the cationic nitrogen atoms linked to the ethanedyl or propanediyl through a degradable group, such as an ester group. In one embodiment, where Ra is Ml / a / ZUZZ / UU l oou R. ° , preferably with X being OH, and / or where Rb is . _r'0, preferably with X being CH, R2 serves as a linker or spacer between the respective piperidine- or piperazine-derived basic ring structure and an ester group. As mentioned, R2 is defined as an alkanedyl having 2 to 8 carbon atoms. R2 may be linear or branched, and otherwise (i.e., barring any branching) is preferably unreplaced. In one embodiment, R2 is a linear alkanedyl substitution having 2, 3, 4, 5, 6, 7, or 8 carbon atoms. In another embodiment, R2 is a linear alkanedyl replacement having 2 to 6 carbon atoms. In another preferred embodiment, R2 is a linear ethanedyl that is not substituted for propanedyl. For example, both Ra and Rb may be < N0, preferably with X being CH, with R2 selected from non-replacing linear alkanediyls having 2 to 6 carbon atoms, such as ethanedyl or propanediyl. In another additional modality, where Ra is ° OO or Or, preferably with X being CH, and / or where Rb is or o0, preferably with X being CH, R2 serves as a linker or spacer between the respective basic piperidine- or piperazine-derived ring structure and an ester group. As mentioned, R2 is defined as an alkanedyl having 2 to 8 carbon atoms. R2 may be linear or branched, and otherwise (i.e., barring any branching) is preferably unreplaced. In one embodiment, R2 is a linear alkanedyl substitution having 2, 3, 4, 5, 6, 7, or 8 carbon atoms. In another embodiment, R2 is a linear alkanedyl replacement having 2 to 6 carbon atoms. In another preferred embodiment, R2 is a linear ethanedyl that does not substitute propanedyl. For example, both R2 and Rb can be 0, preferably with X being CH, with an R2 selected from non-replacing linear alkanediyls having 2 to 6 carbon atoms, such as ethanedyl or propanediyl. The optional structure R3 includes an ester group that can further enhance the degradability of the cationic lipid into smaller molecular species under physiological, e.g., intracellular, conditions. As defined above, R3, if present, is defined, inter alia, as -R5C(O)-O- or -R5-OC(O)-, where R5 may be a spacer consisting of an alkanediyl with 1 to 6 carbon atoms. In other words, the ester group may have any orientation. Preferably, R5 is an unsubstituted linear alkanediyl with 1, 2, 3, 4, 5, or 6 carbon atoms. In another preferred embodiment, R3 is present and R5 is an unsubstituted linear alkanediyl with 2 or 3 carbon atoms, or with 3 to 6 carbon atoms. R4 is defined as a lipophilic substituent having 12 to 36 carbon atoms. This Ray “tail” end, optionally also of Rb (unless Rb is -R1-N(CH3)2) is believed to provide the degree of lipophilicity normally required for molecules to be able to cross biological membranes. Thus, R4 may, in principle, be of any structure that is substantially lipophilic. For example, a hydrocarbon structure is lipophilic. In one embodiment, R4, in at least one of its occurrences, may consist of only carbon and hydrogen atoms. In a preferred embodiment, R4 represents a linear or branched alkyl or alkenyl, preferably having 12 to 25 carbon atoms. The branched alkyl or alkenyl may optionally have a plurality of side chains, such as 2, 3, 4 or more methyl side chains.In another embodiment, R4 may be an alkyl or alkenyl comprising a single alkyl or alkenyl side chain having, for example, 2 to 10 carbon atoms. For example, R4 may be 1-n-hexyl-n-nonyl (or 7-n-pentadecyl) or 2-n-hexyl-n-decyl. In other embodiments, the lipophilic substituent may optionally include one or more heteroatoms such as O, S, or N. In other embodiments, the lipophilic substituent may optionally include one or more saturated, unsaturated, or aromatic ring structures which may optionally include one or more heteroatoms such as O, S, or N. R4 may also include a small number of heteroatoms such as oxygen atoms, provided that the predominantly lipophilic character is maintained. In one embodiment, R4 comprises one or more oxygen atoms and no other heteroatoms. R4 may also comprise a cyclic structure, such as an aromatic or aliphatic ring structure optionally including one or more oxygen atoms. If present, it is preferred that the heteroatoms and / or the cyclic structure are located towards the optional R3 structure rather than towards the end of the “tail”. In one embodiment, R4 is a lipophilic group derived from tocopherol or tocothreinol. In one embodiment, R4 is a lipophilic group derived from alpha-tocopherol, in particular In particular, if not all of R1, R2, and R5 are linear unsubstituted ethanediyl, A is -SS-, and Ray Rb are identical. A “lipophilic group derived from tocopherol or tocothreinol” as referred to herein includes derivatives of tocopherol and tocothreinol, in particular those derivatives with the structures shown in Scheme 1 below, i.e., derivatives derived from alpha-tocopherol, beta-tocopherol, gamma-tocopherol, delta-tocopherol, alpha-tocothreinol, beta-tocothreinol, gamma-tocothreinol and delta-tocothreinol. Isoform R, R. Alpha (a) CH3 CH3 Beta (P) CH3 H Gamma (y) H CH3 Delta (δ) HH Scheme 1: Tocopherol derivatives have a saturated ethyl chain, whereas tocothreinol derivatives have a polyunsaturated ethyl chain. For both tocopherol and tocothreinol derivatives, the isoforms are defined by R1 and R2, which are selected from CH3 and H. Thus, as shown, if, for example, R1 is CH3 and R2 is CH3, the resulting derivative is the alpha isoform of tocopherol and tocothreinol, respectively (referred to as alpha-tocopherol and alpha-tocothreinol derivatives, respectively). Of course, the OH group is not present in the derivatives, since this is the point of attachment, as shown in the two structures on the left. In a preferred embodiment, in particular of aspect A above, R4 is a linear or branched alkyl or alkenyl having 12 to 25 carbon atoms or is a lipophilic group selected from the group consisting of derivatives of alpha-tocopherol, beta-tocopherol, gamma-tocopherol, delta-tocopherol, alpha-tocothreinol, beta-tocothreinol, gamma-tocothreinol and delta-tocothreinol as shown in Scheme 1. In yet another preferred embodiment, in particular of aspect A above, R4 is a linear or branched alkyl or alkenyl having 12 to 25 carbon atoms or In another preferred embodiment, in particular of aspect A above, R4 is selected from the group consisting of ynaal / a / zuzz / uu / oou As mentioned, X is a carbon atom or a nitrogen atom, independently selected at each occurrence. In one embodiment, X is a carbon atom. In another embodiment, both Ra and Rb are structures comprising X, wherein preferably X is a carbon atom at each occurrence. Alternatively, X is a nitrogen atom; for example, both Ra and Rb are structures comprising X, and in each occurrence, a nitrogen atom is selected for X. Whenever reference is made herein to X being a carbon atom, it is understood that it refers to a carbon atom that is bonded to a hydrogen atom, i.e., CH. In some instances herein, reference is already made to X being CH. According to another specific embodiment, a cationic lipid having formula (I) is provided wherein R is selected from vr^n^ ° ,0, preferably with X being CH, or -R1-N(H)-C(O)-R3-R4; where Rb is selected from . Y / X λNI ''x-'S-'Y'ú0, preferably with X being CH, -R1-N(H)-C(O)-R3-R4, or -R1-N(CH3)2; where A is -S-, -SS-, -NH-C(O)-, -NH-C(O)O-, -NH-C(O)-NH-, -SC(O)-N(H)-, 0(0)0- or -OP(O)(OH)-O-; wherein R1 is an optionally substituted linear or unbranched ethanedyl, propanedyl, butanedyl, or alkanedyl having 2 to 8 carbon atoms; where R2 is an alkanedyl having 2 to 8 carbon atoms; where R3 is optional, and if present, is -R5-C(O)-O-, -R5-OC(O)-, -R5-C(O)-NH, -R5-OC(O)-NH-, or R5-NH-C(O)O-; where R4 is a lipophilic substituent with 12 to 36 carbon atoms; where R5 is an alkanedyl having 3 to 6 carbon atoms; where X is a carbon or nitrogen atom; and where all selections are independent of each other. Optionally, the alkanedyls represented by R2 and / or R5 are linear and unsubstituted. According to another specific embodiment, a cationic lipid of formula (I) is provided wherein Rase is selected from MA / a / ¿U¿¿ / UU l oou or , or , preferably with X being CH, or-R1-N(H)-C(O)-R3-R4; where Rbse is selected from 0, preferably with X being CH, -R1-N(H)-C(O)-R3-R4, or -R1-N(CH3)2; where A is -S-, -SS-, -NH-C(O)-, -NH-C(O)O-, -NH-C(O)-NH-, -SC(O)-N(H)-, C(O)O-, or -OP(O)(OH)-O-; wherein R1 is an optionally substituted linear or unbranched ethanedyl, propanedyl, butanedyl, or alkanedyl having 2 to 8 carbon atoms; where R2 is an alkanedyl having 2 to 8 carbon atoms; where R3 is optional, and if present, is -R5-C(O)-O-, -R5-OC(O)-, -R5-C(O)-NH, -R5-OC(O)-NH-, or R5-NH-C(O)O-; where R4 is an alkyl or alkenyl having 12 to 25 carbon atoms; where R5 is an alkanedyl having 1 to 6 carbon atoms; where X is a carbon or nitrogen atom; and where all selections are independent of each other. Optionally, the alkanedyls represented by R2 and / or R5 are linear and unsubstituted. Furthermore, in another embodiment, a cationic lipid according to formula (I) is provided wherein Ray Rbse selected from: AND Υνί0, preferably with X being CH, or -R1-N(H)-C(O)-R3-R4; A is -S-, -SS-, -NH-C(O)-, -NH-C(O)O-, -NH-C(O)-NH-, -SC(O)-N(H)-, -C(O)O-, or -OP(O)(OH)-O-; R1 is an optionally substituted linear or unbranched ethanedyl, propanedyl, butanedyl, or alkanedyl having 2 to 8 carbon atoms; R2 is an alkanedyl having 2 to 8 carbon atoms; R3 is optional, and if present, is -R5-C(O)-O-, -R5-OC(O)-, -R5-C(O)-NH-, -R5OC(O)-NH-, or R5-NH-C(O)O-; R4 is a lipophilic substituent with 12 to 36 carbon atoms; R5 is an alkanedyl having 1 to 6 carbon atoms; X is a carbon or nitrogen atom; where all selections are independent of each other, optionally provided that if R1, R2, and R5 are all unsubstituted linear ethanedyl, A is -SS-, and Rb are identical, then R4 is not In this embodiment, the alkanedyls represented by R2 and / or R5 may be linear and unsubstituted; optionally, R5 comprises 2 to 6 carbon atoms, and each of Ray Rbson r' VN ik 2^0 4 YR0.preferably with X being CH. In another more specific embodiment, a cationic lipid according to formula (I) is provided wherein each of Ray Rbes: .preferably with X being CH; A is -SS-; R1 is an optionally substituted linear or unbranched ethanedyl, propanedyl, butanedyl, or alkanedyl having 2 to 8 carbon atoms; R2 is an alkanedyl having 2 to 8 carbon atoms; R3 is optional, and if present, is -R5-C(O)-O- or -R5-OC(O)-; R4 is a lipophilic substituent with 12 to 36 carbon atoms; R5 is an alkanedyl having 2 to 6 carbon atoms; X is a carbon or nitrogen atom; where all selections are independent of each other, optionally provided that if R1, R2, and R5 are all unsubstituted linear ethanedyl, A is -SS-, and Rb and R1 are identical, then R4 is not Again, the alkanedyls represented by R2 and / or R5 can be linear and unsubstituted. Another additional embodiment provides a cationic lipid according to formula (I) wherein each of Ray Rbes: or .preferably with X being CH; A is -SS-; R1 is an optionally substituted linear or unbranched ethanedyl, propanedyl, butanedyl, or alkanedyl having 2 to 8 carbon atoms; R2 is an alkanedyl having 2 to 8 carbon atoms; R3 is optional, and if present, is -R5-C(O)-O- or -R5-OC(O)-; R4 is an alkyl or alkenyl having 12 to 25 carbon atoms; R5 is an alkanedyl having 2 to 6 carbon atoms; X is a carbon or nitrogen atom; and where all selections are independent of each other, and where the alkanedyls represented by R2 and / or R5 can be linear and unsubstituted. In another embodiment, a cationic lipid according to formula (I) is provided, wherein each of Ray Rbes: . .r' X.2,O. _R' . R [And R0, preferably with X being CH; A is -SS-; R1 is an optionally substituted linear or unbranched ethanedyl, propanedyl, butanedyl, or alkanedyl having 2 to 8 carbon atoms; R2 is an alkanedyl having 2 to 8 carbon atoms; R3 is optional, and if present, is -R5-C(O)-O- or -R5-OC(O)-; R4 is an alkyl selected from: R5 is an alkanedyl having 2 to 6 carbon atoms; X is a carbon or nitrogen atom; where all selections are independent of each other, and where the alkanedyls represented by R2 and / or R5 can be linear and unsubstituted. Another additional embodiment relates to a cationic lipid according to formula (I) wherein each of Ray Rbes: VNI0, ​​preferably with X being CH; A is -SS-; R1 is an optionally substituted linear or unbranched ethanedyl, propanedyl, butanedyl, or alkanedyl having 2 to 8 carbon atoms; R2 is an alkanedyl having 2 to 8 carbon atoms; R3 is -R5-C(O)-O- or -R5-OC(O)-; R4es: R5 is an alkanedyl having 2 to 6 carbon atoms; X is a carbon or nitrogen atom; where Ray Rb are identical and the other selections are independent of each other, and where the alkanedyls represented by R2 and / or R5 can be linear and unsubstituted. In yet another embodiment, the invention provides a cationic lipid according to formula (I) wherein each of Ray Rbes: r' And ni ινΐΛ / a / zuzz / uu / oou 0, preferably with X being CH; A is -SS-; R1 is an optionally substituted linear or unbranched ethanedyl, propanedyl, butanedyl, or alkanedyl having 2 to 8 carbon atoms; R2 is an alkanedyl having 2 to 8 carbon atoms; R3es-R5_c(Q)-O-; R4es: h3c R5 is an alkanedyl having 2 to 6 carbon atoms; X is a carbon or nitrogen atom; where Ray Rb are identical and the other selections are independent of each other, and where the alkanedyls represented by R2 and / or R5 can be linear and unsubstituted. According to another additional embodiment, the cationic lipid provided by the present invention is a compound of formula (I), wherein each of Ray Rbes: 0, preferably with X being CH; A is -SS-; R1 is an optionally substituted linear or unbranched ethanedyl, propanedyl, butanedyl, or alkanedyl having 2 to 8 carbon atoms; R2 is an alkanedyl having 2 to 8 carbon atoms; r3es_R5_c(O)-O-; R4es: h3c or > your NCNNCC σ ac R5 is an alkanedyl having 2 to 6 carbon atoms; X is a carbon atom; where Ray Rb are identical and the other selections are independent of each other, and where the alkanedyls represented by R2 and / or R5 can be linear and unsubstituted. In another specific embodiment, the cationic lipid provided by the invention is a compound according to formula (I), wherein each of Ray Rbes: r' VN7 Or, preferably with X being CH; A is -SS-; R1 is ethanedyl; R2 is an alkanedyl having 2 to 8 carbon atoms; R3 is -R5 -C(O)-O-; R4es: h3c R5 is an alkanedyl having 2 to 6 carbon atoms; X is a carbon atom; where Ray Rb are identical and the other selections are independent of each other, and where the alkanedyls represented by R2 and / or R5 can be linear and unsubstituted; preferably, also the ethanedyl of R1 is linear and unsubstituted. In another preferred embodiment, the cationic lipid has one or more of the following characteristics, independently selected in each occurrence: (i) R1 is an unsubstituted ethanedyl, propanedyl or butanedyl; (i) R2 is a linear, unbranched alkanedyl having 2 to 8 carbon atoms; (i¡) R3es-R5-C(O)-O- or -R5-OC(O)-; (iv) R4 is an alkyl or alkenyl having 12 to 25 carbon atoms; (v) R5 is an alkanedyl having 2 to 6 carbon atoms; and / or (vi) X is a carbon atom. In another preferred embodiment, in particular of the above aspect A, R is present and is selected from the group consisting of -R-C(O)-O-, -R-OC(O)-, -R-C(O)-NH-, -R-OC(O)-NH-, and RNH-C(O)O-; and R is a linear or branched alkyl or alkenyl having 12 to 25 carbon atoms. In this embodiment, it may be particularly preferred that R is -R-C(O)-O- or -R-OC(O)-. In this embodiment, it may be further preferred that R is selected from the group consisting of ινΐΛ / a / zuzz / uu i oou In yet another preferred embodiment, in particular of the above aspect A, A is -S-. In this embodiment, it may be preferred that Ray Rb are identical and are 0with X preferably being CH. It may be even more preferred in this embodiment that R3 is present and selected from -R5-C(O)-O- or -R5-OC(O)-. It may also be preferred in this embodiment that R4 is . It may be even more preferred in this embodiment that R4 of Ray and R4 of Rb are identical. Finally, it is also preferred in this embodiment that one or all of R1, R2 and R3 are alkanedyl having 1 to 6 carbon atoms, in particular having 2, 3 or 3 carbon atoms. In yet another further embodiment, the cationic lipid is preferably selected from the cationic lipids as listed in Table 1. Table 1: Preferred cationic lipids according to formula (I) - when referring to specific lipids in this table, reference is made to Lipid C1, Lipid Compound 1 or C1 Cationic Lipid Compound No. Structure Ref. in Figures / Name C18 o O lily IIIII 0 0 2DPhy-C5DEPipSS C19 / \ o ) \__ / / o λ oc ω _ -zr / Vit E-C5DE- Pip-TEN C20 WATER 1 ........j 1 / 1 . .___ rt — . 1 1 Ί. ... ϊ i ϊ ” Ϊ '1 1 HEXA-C5DEPip-Phosphate C22 Γ ji L jj 'Y ' Y'' HEXA-C5DEPip-Thioether MA / a / ¿U¿¿ / UU / oou C25 HEXA-C5DEPip-C3 thioether o HEXAC5DEpiperide ina-C3 thioether ινΐΛ / a / zuzz / uu / oou C26 THIOETHER or VitE-C4DEPiperidineToether MA / a / ¿U¿¿ / UU l oou Consequently, the invention relates to a composition comprising the previously described cathlonic lipid. For example, the composition may comprise a cationic lipid selected from compounds C1 to 027 déla Table 1 . In certain additional embodiments, the cationic or cationizable lipid may be any of a number of lipid species that comprise a tertiary or quaternary nitrogen / amino group or that carry a net positive charge at a selective pH, such as physiological pH.Consequently, in one way, a cationic lipid that includes a tertiary or cuaternary nitrogenic / amino group or a cationic lipid that raises a positive net charge at physiological pH is selected, among others, from the group that consists of Ν,N-dioleyl-N N-dimethylammonium chloride (DODAC); N-(2,3-dioleyloxy)propyl)-N,N,N-trimethylammonium chloride (DOTMA); N,Nd¡estear¡lN,N-dimethylammonium bromide (DDAB); N-(2,3dioleoylox¡)prop¡l)-N,N,Ntrimethylammonium chloride (DOTAP); 3-(N-(N',N'dimethylamyl)-carbamoyl)cholesterol (DC-Chol); N-(1-(2,3dioleoloxypropyl)N-2-(hespermanacarboxamide)ethyl)-N,N-dimethylammonium trifluoroacetate (DOSPA); dioctadecylamidoglycyl carboxyspermine (PERROS); 1,2-doleol-3-dimethylammonium propane (DODAP); N,Ndmethyl-2,3-dioleoloxypropyl)lamine (DODMA); and N-(1,2dmrstoxypropyl)-N,Ndmethyl-Nhydroxyethylammonium bromide (DMRIE). In a further embodiment, a cationic lipid comprising a tertiary or quaternary nitrogen / amino group or a cationic lipid carrying a net positive charge at physiological pH is selected from, but not limited to, the group consisting of amino lipids. In another embodiment, suitable amino lipids include those described in WO 2012 / 016184 A2, incorporated herein by reference in its entirety. Other additional cationic lipids suitable for use in the compositions include cholesterol-based cationic lipids. Other representative aminolipids include, but are not limited to (i) those having the formula: IVIA / a / ZUZZ / UU l oou wherein Ri and R2 are the same or different and independently C10-C24 optionally substituted alkyl, C10-C24 optionally substituted alkenyl, C10-C24 optionally substituted alkynyl or C10-C24 optionally substituted acyl; R3 and R4 are the same or different and independently C1-C6 optionally substituted alkyl, C2-C6 optionally substituted alkenyl or C2-C6 optionally substituted alkynyl or R3 and R4 may join to form an optionally substituted heterocyclic ring of 4 to 6 carbon atoms and 1 or 2 heteroatoms chosen from nitrogen and oxygen; R5 is absent or present and when present is hydrogen or C1-C6 alkyl; m, n and p are equal or different and independently 0 or 1 provided that m, n and p are not simultaneously 0; q is 0, 1, 2, 3, or 4; and Y and Z are equal or different and independently 0, S, or NH. In one embodiment, R1 and R2 are each linoleyl, and the aminolipid is a dilinoleyl aminolipid; (¡i) the selected ones from the group that consists of dilinoleil amino lipid; 1,2-dilinoleyoxy3-(dimethylamino)acetox¡propane (DLin-DAC); 1,2-dilinoleoxy-3morphol¡nopropane (DLin-MA); 1,2dilinoleoyl-3-dimethylaminopropane (DLinDAP); 1,2-dilinole ¡lt¡o-3-dime¡lam¡nopropane (DLin-S-DMA); 1linoleo¡l-2-l¡nole¡lox¡-3d¡met¡laminopropane (DLin-2-DMAP); 1,2-dllinolexlox-3trimethylaminopropane chloride salt (DLin-TMA.CI); 1,2-d¡linoleo¡l-3-tr¡methylam¡nopropane chloride salt (DLinTAP.CI); 1,2-dil¡nole¡lox¡-3-(N-meth¡lp¡perazino)propane (DLin-MPZ); 3-(N,Ndilinoleylamino)-1,2propanodiol (DLinAP); 3-(N,N-dioleilam¡no)-1,2-propanod¡ol (DOAP); 1,2-dilinoleyloxo-3-(2-N,Ndimethylamino)ethoxypropane (DLin-EG-DMA); 2,2-dilinoleyl-4-dimethylaminomethyl-[1,3]-dioxolane (DLin-KDMA); y DLin-KC2-DMA (DLin-K-DMA anterior, where n es 2). The cationic lipids described herein may exist in the form of salts, for example, acid addition salts or, in certain cases, salts of organic and inorganic bases such as carboxylate, sulfonate, and phosphate salts. All such salts are within the scope of this invention, and references to cationic lipids and compounds of formula (I) and subsets thereof include the salt forms of the compounds. In a further embodiment, commercially available preparations of cationic lipids can be used in the present invention. These include, for example, LIPOFECTIN® (commercially available cationic liposomes comprising DOTMA and 1,2-doleoyl-sn-glycero-3-phosphoethanolamine (DOPE), available from GIBCO / BRL, Grand Island, NY); LIPOFECTAMINE® (commercially available cationic liposomes comprising N-(1-(2,3-doleoyloxy)propyl)-N-(2-(sperminecarboxamido)ethyl)-N,Nd-methylammonium trifluoroacetate (DOSPA) and DOPE, available from GIBCO / BRL); and TRANSFECTAM® (commercially available cationic lipids comprising dioctadecylamidoglycyl carboxyspermine (DOGS) in ethanol available from Promega Corp., Madison, WI). In a further embodiment, the compositions include an imidazole cholesterol ester or “ICE” as described in paragraphs

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[0340] of WO 2019226925 A1 , which is incorporated herein by reference in its entirety. Other suitable (cationic) lipids are disclosed in WO2009 / 0865558 , WO2009 / 127060 , WO2010 / 048536 , WO2010 / 054406 , WO2010 / 088537 , WO2010 / 129709, WO2011 / 153493, US2011 / 025612, US22012, US22512, US222512251251 2512251 251, WO2016118724, WO2016118725, WO2017070613, WO2017070620, WO2017099823 and WO2017112865; all of which are incorporated herein by reference in their entirety. In some embodiments, the cationic lipid is selected from the group consisting of 98N12-5, C12-200 and ckk-E12 as described in WO2017049074, US9512073B2, WO2015200465, US20150376144; all of which are incorporated herein by reference in their entirety. The cationic lipid may comprise from about 20 mol % to about 70 or 75 mol % or from about 45 to about 65 mol % or about 20, 25, 30, 35, 40, 45, 50, 55, 60, 65 or about 70 mol % of the total lipid present in the lipid composition or nanoparticle of the invention. In another embodiment, the lipid nanoparticles include from about 25% to about 75% on a molar basis of cationic lipid, for example, from about 20 to about 70%, from about 35 to about 65%, from about 45 to about 65%, about 60%, about 57.5%, about 57.1%, about 50%, or about 40% on a molar basis (based on 100% total moles of lipid in the lipid nanoparticle). In general, the composition according to the invention may comprise other excipients, such as one or more lipids. In one embodiment, a composition may comprise an additional cationic lipid, i.e., a second, third cationic lipid, and so on. Said additional cationic lipid may optionally be a cationic lipid as described herein. Alternatively, it may be any other cationic lipid suitable for pharmaceutical compositions, in particular for compositions comprising an active ingredient selected from nucleic acid compounds, such as mRNA. In a specific embodiment, the additional cationic lipid is a permanent cationic lipid comprising at least one quaternary nitrogen atom. In this case, the first cationic lipid is preferably a lipid that is cationizable rather than permanently cationic. Pharmaceutically acceptable salts of the basic cationic lipid may be derived from inorganic or organic acids. For example, from inorganic acids such as hydrochloric, hydrobromic, sulfuric, sulfamic, phosphoric, nitric acid and the like, as well as salts of organic acids such as acetic, propanoic, succinic, glycolic, stearic, lactic, malic, tartaric, citric, ascorbic, pamoic, maleic, hydroxymaleic, phenylacetic, glutamic, benzoic, salicylic, sulfanilic, 2-acetoxybenzoic, fumaric, toluenesulfonic, methanesulfonic, ethanesulfonic, naphthalenesulfonic, benzenesulfonic, trifluoroacetic and the like. Other examples of pharmaceutically acceptable salts include, but are not limited to, mineral or organic acid salts of basic residues such as amines; alkaline or organic salts of acid residues such as carboxylic acids; and the like.Representative alkali metal or alkaline earth metal salts include sodium, lithium, potassium, calcium, magnesium, and the like, as well as non-toxic ammonium, quaternary ammonium, and amine cations, including but not limited to ammonium, tetramethylammonium, tetraethylammonium, methylamine, dimethylamine, trimethylamine, triethylamine, ethylamine, and the like. Pharmaceutically acceptable salts herein. IVIA / a / ZUZZ / UU The disclosure includes conventional non-toxic salts of the parent compound formed, for example, from non-toxic inorganic or organic acids. The pharmaceutically acceptable salts of the present disclosure can be synthesized from the parent compound containing a basic or acid moiety by conventional chemical methods. In general, such salts can be prepared by reacting the free acid or base forms of these compounds with a stoichiometric amount of the appropriate base or acid in water or an organic solvent, or a mixture of both; generally, non-aqueous media such as ether, ethyl acetate, ethanol, isopropanol, or acetonitrile are preferred. Lists of suitable salts are found in Remington's Pharmaceutical Sciences, 17th ed., Mack Publishing Company, Easton, Pa., 1985, p. 1418, Pharmaceutical Salts: Properties, Selection, and Use, PH Stahl and CG Wermuth (eds.), Wiley-VCH, 2008, and Berge et al., Journal of Pharmaceutical Science, 66, 1-19 (1977), each of which is incorporated herein by reference in its entirety. i) Polymer-conjugated lioid, embezzled lioid In some embodiments, the LNPs comprise a lipid conjugate, preferably a polymer-conjugated lipid. The term “polymer-conjugated lipid” refers to a molecule comprising both a lipid portion and a polymer portion. Preferably, the polymer-conjugated lipid is a pegylated lipid or PEG-lipid. The terms “pegylated lipid” or “PEG-lipid” refer to a molecule comprising both a lipid portion and a polyethylene glycol portion. PEGylated lipids are known in the art and include PEG-DMG and the like. In a specific embodiment, the polymer-conjugated lipid is defined as a compound according to formula (II): PAL formula (II) where P is a hydrophilic polymeric moiety, A is an optional linker or spacer and L is a lipid moiety. Hydrophilic polymer fraction P The hydrophilic polymer moiety P in the polymer-conjugated lipid according to formula (II) may be a polyethylene glycol (“PEG”) moiety. In a specific embodiment, the PEG moiety has an average molecular mass of between 1 kDa and 3 kDa, for example, between 1.5 and 2.5 kDa, between 1.7 and 2.3 kDa, between 1.8 and 2.2 kDa, between 1.9 and 2.1 kDa, or 2 kDa. Thus, the PEG may be a PEG that is commonly known as “PEG 2000” or “PEG 2k,” although the shorter “PEG 1000” and the longer “PEG 3000” may also be used. The PEG moiety typically comprises linear polymer chains, but in some embodiments, the PEG moiety may comprise branched polymer chains. Alternatively, contemplated PEG-modified lipids include, but are not limited to, a polyethylene glycol chain of up to 2 kDa, up to 3 kDa, up to 4 kDa, or up to 5 kDa in length convalently linked to a lipid. In another embodiment, the hydrophilic polymer moiety P in the polymer-conjugated lipid may also be a substantially hydrophilic polymer which is different from the hydrophilic polymer moieties described above, i.e., the hydrophilic polymer moiety P in the polymer-conjugated lipid may be based on polypropylene oxide), poly(vinylpyrrolidone), poly(vinyl alcohol), poly-N-(2-hydroxypropyl)methacrylamide, a hesylation process (according to PMID 24681396), a polymerization approach. PASylation (i.e., proline-alanine-serine), an XTEN approach as known in the art (i.e., peptide-based PEG), polysarcosina or poly(vinyl acetate). Optional linker or spacer A The optional linker or spacer A in the polymer-conjugated lipid according to formula (II) may be any useful spacer structure, such as a spacer selected from those that have generally been found useful in pegylated lipids, for example, but not limited to, succinimide, amine, ether, ester, anhydride, aldehyde, ketone, amide, carbamate linkers, or combinations thereof. Lyophilized fraction L The lipid moiety L in the polymer-conjugated lipid according to formula (II) may be derived from a phospholipid, a sphingolipid, or a ceramide. As used herein, the term “derivative of a phospholipid or a ceramide” includes phospholipid and ceramide moieties. Examples are polymer-conjugated lipids comprising a phosphatidylethanolamine or phosphatidylglycerol moiety. In a specific embodiment, the polymer-conjugated lipid is a pegylated lipid. In a more specific embodiment, the polymer-conjugated lipid comprised in the composition of the invention is a polymer-conjugated lipid selected from the group consisting of a pegylated diacylglycerol lipid (PEG-DAG); a pegylated ceramide lipid (PEG-Cer); a pegylated dephosphatidylethanolamine lipid (PEG-PE); a pegylated diacylglycerol succinate lipid (PEG-S-DAG); a pegylated dialkoxypropyl carbamate lipid; 1,2-dimíristoyl-rac-glycero-3-methoxypolyethylene glycol (“PEG-DMG” or “DMG-PEG'j; 1,2-dicapryl-rac-glycero-3methylpolyoxyethylene glycol (C10 diacylglycerol PEG); N-octanoyl-sphingosine-1{succin¡l[methoxy(polyét¡lenglycol)2000]} (comprising N-octanoyl-D-erythro-sphingosine (d18:1 / 8:0), also called PEG-Ceramid8, C8-ceramide-PEG, PEG-Cer8, Cs PEG2000 Ceramide or Ceramide 8 PEG);4-0-(2',3'-d¡(tetradecan¡loxi)prop¡l-1-0-(ω-methox¡(poliethox¡)et¡l)butanodi¡oate (PEG-S-DMG); 2mPEG2000-n,n ditetradecylacetamida; N- [(methoxypoly(ethylene licol)2000)carbamyl]-1,2-d¡m¡r¡loxl-3amina (PEG-c-DMA); WO2020093061 or WO2020219941 (the three references are incorporated here as reference), PEGylated cholesterol or a PEGylated decholesterol derivative as described in this document, and 2,3-di(tetradecanox¡)propyl- N-(m-methoxl(pol¡etoxi)et¡l)carbamate. ωmethox¡(pol¡ethoxi)ethyl-N-(2,3-d¡(tetradecanoxy)prop¡l)carbamate; a PEG lipid as described in the documents WO2018126084, WO2020093061 or WO2020219941 (the three references are incorporated here as a reference), PEGylated cholesterol or a derivative of PEGylated cholesterol as is described in this document, and 2,3-d¡(tetradecanol¡)prop¡l N-(ω-methox¡(polyethox)et¡l)carbamate.; In another preferred embodiment, the lipid fraction L comprises 1, 2, 3, 4 or more hydrophobic fatty acids (“tails”, corresponding to aliphatic chains comprising an even number of carbon atoms). In a more preferred embodiment, the lipid fraction L comprises 2 hydrophobic fatty acids (“tails”) having the same or different numbers of carbon atoms. Preferably, the lipid fraction L comprises a fatty acid (“tail”) comprising, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25 or 26 carbon atoms or combinations thereof. More preferably, the lipid fraction L comprises a fatty acid (“tail”) comprising 8, 9, 10, 11, 12, 13, 14, 15, 16, 17 or 18 carbon atoms or combinations thereof. In a more specific embodiment, the lipid fraction L comprises a fatty acid (“tail”) selected from the group consisting of caprylic acid or octanoic acid (8:0); capric acid (10:0); lauric acid (12:0); myristic acid (14:0); palmitic acid (16:0); stearic acid (18:0); arachidic acid (20:0); behenic acid (22:0); lignoceric acid (24:0); and cerotic acid (26:0). In an even more preferred embodiment, the lipid fraction L comprises at least one fatty acid (“tail”) comprising 8, 10 or 12 carbon atoms, preferably 8 or 10 carbon atoms. IVIA / S / ZUZZ / UU / oou In another preferred embodiment, the composition comprises the lipid conjugated with polymer -1,2-dimyristoyl-rac-glycero-3-methoxypolyethylene glycol 2000 (DMG-PEG 2000) Preferably, and as used in the art, “DMG-PEG 2000” is considered a mixture of 1,2-DMG PEG2000 and 1,3-DMG PEG2000 in a ratio of -97:3. In a further specific embodiment, the composition comprises a polymer-conjugated lipid selected from the group consisting of - 1,2-dicapril-rac-glycero-3-methylpolyoxyethylene glycol 2000 (C10-PEG 2000) EITHER - N-octanoyl-sphingosine-1-{succinyl[methoxy(polyethylene glycol)2000]} (Cer8-PEG 2000) In a further embodiment, the composition comprises a polymer-conjugated lipid selected from the group consisting of the following structure resembling “Cs-PEG 2000” having the following chemical structure: oou In specific embodiments of the invention, each composition as described herein within the specification comprising “Cw-PEG 2000” may also be formulated with “Cs-PEG 2000” instead of “C10-PEG 2000”. Thus, as an example, a polymer-conjugated lipid, or respectively a lipid fraction L, may have two fatty acid tails, comprising saturated fatty acids, unsaturated fatty acids or a combination thereof (“tails”), such as Cer8-PEG 2000 comprising a saturated fatty acid chain (8:0; caprylic acid or respectively octanoic acid) and an unsaturated fatty acid chain of different lengths with more than 8 carbon atoms. Specifically, the advantageous use of lipids conjugated to polymers with shorter alkyl chains (f.e. Cer8) as described herein, preferably in combination with the inventive lipids as described herein as in Table 1 and / or DPhyPE as neutral lipid instead of DSPC, to deliver live mRNA vaccines, resulting in significantly enhanced immune responses is another very surprising finding made by the inventors and resembles specific aspects and embodiments of the present invention. ii) Spheroid A "steroid" is an organic compound with four rings arranged in a specific molecular configuration. It comprises the following carbon skeleton: Steroids and neutral steroids include both naturally occurring steroids and analogs thereof (e.g., unpathogenic lipid cholesterol hemisuccinate (CHEMS) consisting of succinic acid esterified to the beta-hydroxyl group of cholesterol as a cholesterol derivative). Using the definition of “neutral” provided herein, the neutral steroid can be a steroid that has no atoms or groups that are ionizable under physiological conditions, or it can be a zwitterionic steroid. In a preferred embodiment, the neutral steroid is free of atoms or groups that are ionizable under physiological conditions. In some preferred embodiments, the steroid or steroid analog is cholesterol. The terms “steroid” and “neutral steroid” are used interchangeably herein. In another embodiment, the steroid is an imidazole cholesterol ester or “ICE” as described in paragraphs

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[0340] of WO 2019226925 A1 ; which is incorporated herein by reference in its entirety. i oou ¡ii) Neutral lipid, neutral phospholipid A “neutral lipid,” also referred to as a “helper lipid” according to the invention, is preferably a phospholipid or a neutral phospholipid. As used herein, a “neutral phospholipid” is an amphiphilic compound consisting of molecules typically having two hydrophobic fatty acid “tails” and a hydrophilic “head” comprising a phosphate group. The phosphate group can be modified with simple organic molecules such as choline, ethanolamine, or serine. Phospholipids are found in abundance in nature. For example, they represent a significant fraction of the excipients of biological membranes. As used herein, the term “phospholipid” or “neutral phospholipid” covers both natural and synthetic phospholipids. The terms “neutral lipid,” “neutral phospholipid,” or “zwitterionic compound,” as used interchangeably herein, refer to any of several lipid species that exist in a neutral or uncharged zwitterionic form at physiological pH. Representative neutral lipids include diacylphosphatidylcholines, diacylphosphatidylethanolamines, ceramides, sphingomyelins, dihydrosphingomyelins, cephalins, and cerebrosides as described hereinafter. According to one preferred embodiment, the composition comprises a neutral lipid that is zwitterionic, such as a phosphatidylcholine or a phosphatidylethanolamine. Examples of suitable phosphatidylcholines include native or purified mixtures, sometimes referred to as “lecithin” or “phosphatidylcholine,” often derived from egg yolk or soybeans; or highly purified or semi-synthetic compounds such as phosphatidylcholines having two fatty acyl moieties selected from myristoyl, palmitoyl, stearoyl, oleoyl, and the like. In another preferred embodiment, the neutral lipid or neutral phospholipid is a zwitterionic compound selected, inter alia, from the group of 1,2-diphytanoyl-sn-glycero-3-phosphoethanolamine (DPhyPE; also referred to as 1,2-d¡-(3,7,11,15-tetramethylhexadecanoyl)-sn-glycero-3-phosphoethanolamine), 1,2-diphytanoylsn-glycero-3-phosphocholine (DPhyPC), 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC; also referred to as dioleoylphosphatidylcholine), 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC, also referred to as dipalmitoylphosphatidylcholine), 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), phosphatidylethanolamines, distearoyl phosphatidyl ethanolamines, dioleoyl-phosphatidylethanolamine (DOPEA), 1,2-distearoyl-sn-glycero-3phosphoethanolamine (DSPE), palmitoyloleoylphosphatidylcholine (POPC), palmitoyloleoyl-phosphatidylethanolamine (POPE), 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE), dioleoyl-phosphatidylethanolamine 4-(N-maleimidomethyl)cyclohexane-1-carboxylate (DOPE-mal), 1,2-Dimyristoyl-sn-glycero-3-phosphoethanolamine (DMPE), 1,2-dilinoleoylsn-glycero-3-phosphoethanolamine (DLoPE), distearoyl-phosphatidylethanolamine (DSPE), 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (POPE), 1,2-dilauroyl-sn-glycero-3-phosphoethanolamine (DLPE), 16-0monomethylphosphoethanolamine, 16-O-dimethylphosphatidylethanolamine, 1,2-dierucoyl-sn-glycero-3-phosphoethanolamine (DEPE), 18-1-trans phosphatidylethanolamine, 1-stearoyl-2-oleoylphosphatidethanolamine (SOPE), 1,2-Disqualeoyl-sn-glycero-3-phosphoethanolamine (DSQPE), 1,2-dielaidoyl-sn-glycero-3-phosphoethanolamine (transDOPE), 1-Stearoyl-2 linoleoyl-sn-glycero-3-phosphoethanolamine (SLPE), 1-tr¡decane¡l-sn-glycero-3-phospho-L-serine (disodium salt), 1-oleoyl2-hydroxy¡-sn-gl¡cero-3-phospho-L-ser¡na (sodium salt), 1-palmitoyl-2-oleoyl-sn-gl¡cero-3-phospho-L-ser¡na (sodium salt) (POPS), 1-1-stearoyl-2-oleoyl-sn-glycero-3-phospho-L-serine (sodium salt), 1,2-dioleoyl-sn-glycero-3-phosphoL-serine (sodium salt) (DOPS), 1,2-diestearoyl-sn-glycero-3-phospho-L-ser¡na (sodium salt), 1,2-diphytanoyl-snglycero-3-phospho-L-serine (sodium salt), 1-O-hexadecanyl-2-O-(9Z-octadecenyl)-sn-glycero-3-phosphoethanolamine, 1,2-diestearoyl-sn-glycero-3-phosphatidylcholine or 1,2-diestearoyl-sn-glycero-3-phosphocol¡na (DSPC), 1,2-di-O-phytanilosn-glycero-3-phosphoethanolamine, 1-palmitoyl-2-cholester¡lhem¡succ¡no¡l-sn-gl¡cero-3-phosphocol¡na(PChemsPC), 1,2diclesterylhemisuccinoyl-sn-glycero-3-phosphacholine (DChemsPC), 2-((2,3-bis(oleo¡lox¡)prop¡l)d¡met¡lamon¡o)ethyl hydrogen phosphate (DOCP), 2-((2,3-bis(oleoylox¡) phosphate de propyl)dimtheylamonium)ethylethyl (DOCPe) y 1-0octadecyl-2-O-methyl-sn-glycero-3-phosphacholine (Edelfosine)., In a preferred embodiment, the neutral lipid according to the invention is 1,2-Dipalmitoyl-sn-glycero-3-phosphocholine (D PPG), 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) or 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE). In a more preferred embodiment, the neutral lipid according to the invention is 1,2-diphytanoyl-sn-glycero-3-phosphocholine (DPhyPC). In an even more preferred embodiment, particularly preferred, the neutral lipid according to the invention is 1,2-diphytanoyl-sn-glycero-3-phosphoethanolamine (DPhyPE). The inventive advantage related to the use of DPhyPE is the high fusogenic capacity due to its bulky tails, whereby it is capable of fusing at a high level with endosomal lipids. Specifically, the advantageous use of 1,2-diphthanol-sn-glycero-3-phosphoethanolamine (DPhyPE) as described herein, preferably in combination with the inventive lipids as described herein in Table 1, specifically for delivering mRNA vaccines in vivo, resulting in enhanced immune responses, is a surprising finding of the inventors that resembles specific aspects and embodiments of the present invention. In other words, the inventors surprisingly discovered that the use of DPhyPE provided a distinct advantage over DSPC, which to date is used in the art as the standard neutral lipid in nearly all state-of-the-art LNP compositions for mRNA and also siRNA, specifically, but not limited to, vaccination settings.In other words, the compositions of the invention have highly advantageous and unexpected in vivo behavior resulting in highly enhanced immune responses. Interestingly, the inventors found that compositions comprising DPhyPE instead of DSPC displayed superior expression profiles in vitro and in vivo, even when compared to the GN01 composition. Consequently, it was surprisingly discovered that the use of DPhyPE provided a distinct advantage over DSPC, which to date is used in the art as the standard neutral lipid in almost all state-of-the-art LNP compositions. Importantly, the inventors found that one of the advantageous features of the inventive compositions and lipid nanoparticles, such as the GN01 formulation, is that it is capable of inducing strong CD8+ T cell responses. This is due to the fact that, in the case of malaria, since CD8+ T cells are an important immune mechanism of protection against intracellular infections caused by malaria parasites, an effective malaria vaccine should induce strong CD8+ T cell responses. ynaal / a / zuzz / uu / oou Furthermore, the data presented in the Examples demonstrate significant enhanced immune responses using the compositions of the invention, i.e., all RNA vaccines of the invention are useful according to the invention. Surprisingly, in contrast to prior art knowledge showing that DSPC is the most common and unquestionable neutral lipid for lipid nanoparticles, the inventors found that it is preferable to use DPhyPE for mRNA formulations in compositions for vaccine production. Surprisingly, the inventors have also discovered that the addition of at least one additional neutral lipid to the above neutral lipid, in particular a second neutral lipid, can also enhance immune responses (see Figures 28 to 31 and corresponding examples). As indicated above, it is preferred that the (first) neutral lipid of the invention has two fatty acyl moieties selected from myristoyl, palmitoyl, stearoyl, oleoyl and the like, which in particular means that the fatty acyl moieties are fairly long moieties from moieties with 14 carbon atoms.The inventors discovered that the addition of a neutral lipid with shorter fatty acyl moieties provides beneficial effects, particularly if the additional neutral lipid has two fatty acid moieties selected from pentanoyl, hexanoyl, heptanoyl, octanoyl, nonaoyl and decanoyl, i.e. moieties with at least the majority of the 10 carbon atoms. A particularly preferred additional neutral lipid is 1,2-diheptanoyl-sn-glycero-3-phosphocholine (DHPC), but related neutral lipids, such as 05:0 PC (1,2-dipentanoyl-sn-glycero-3-phosphocholine), 06:0 PC (1,2-dihexanoyl-sn-glycero-3-phosphocholine), 08:0 PC (1,2dioctanoyl-sn-glycero-3-phosphocholine), 09:0 PC (1,2-dinonanoyl-sn-glycero-3-phosphocholine), and 10:0 PC (1,2-dihexanoyl-sn-glycero-3-phosphocholine) may also be used. Therefore, in one aspect of the invention, the lipid nanoparticles of the invention comprise a neutral lipid or ospholipid having at least one alkyl chain with a length of Cs, Ce, C7, Cs, Ce, C10, Cu, C12, C13 or C14, preferably with a length of Ce, C7, Cs, Cs, or C10, more preferably with a length of Ce, C7, Cs, most preferably with a length of C7. In another embodiment of the invention, the lipid nanoparticles of the invention comprise a neutral lipid or phospholipid having at least two alkyl chains, wherein each alkyl chain independently has a length of Cs, Ce, C7, Cs, C9, C10, Cu, C12, C13 or C14, preferably with a length of Ce, C7, Cs, C9, or C10, more preferably with a length of Ce, C7, Cs, most preferably with a length of C7. In a preferred embodiment, the lipid nanoparticles of the invention additionally comprise DHPC.In a further embodiment, one or more alkyl chains may comprise carbon double bonds. In other embodiments, the lipid nanoparticles comprise an additional phospholipid selected from the group consisting of O5:0 PC (1,2-dipentanoyl-sn-glycero-3-phosphocholine), O4:0 PC (1,2-dibutyryl-sn-glycero-3-phosphocholine), O6:0 PC (DHPC, 1,2-dihexanoyl-sn-glycero-3-phosphocholine), O8:0 PC (1,2-dioctanoyl-sn-glycero-3-phosphocholine), and O9:0 PC (1,2-dinonanoyl-sn-glycero-3-phosphocholine). iv) Lipid nanoparticle compositions. The terms “lipid nanoparticle composition” and “composition” are used interchangeably herein. In the context of the present invention, lipid nanoparticles are not restricted to any particular morphology, and should be interpreted as including any morphology generated when a cationic lipid and, optionally, one or more additional lipids are combined, for example, in an aqueous environment and / or in the presence of a nucleic acid compound. For example, a liposome, a lipid complex, a lipoplex, and the like are within the scope of a lipid nanoparticle. In the context of the invention, a “composition” refers to any type of composition wherein the specified ingredients may be incorporated, optionally together with other excipients, typically with at least one pharmaceutically acceptable carrier or excipient. Thus, the composition may be a dry composition such as a powder or granules, or a solid unit such as a lyophilized form or a tablet. Alternatively, the composition may be in liquid form, and each excipient may be incorporated independently in dissolved or dispersed (e.g., suspended or emulsified) form. In one preferred embodiment, the composition is formulated as a sterile solid composition, such as a powder or lyophilized form for reconstitution with an aqueous liquid vehicle. In the composition of the invention, the cationic lipid may be present within or as part of lipid nanoparticles (LNP). In other words, said composition comprises lipid nanoparticles and the cationic lipid is present in the lipid nanoparticles. A “nanoparticle,” as used herein, is a submicron particle having any structure or morphology. Submicron particles may also be referred to as colloids or colloidal particles. With respect to the material on which the nanoparticle is based, and the structure or morphology, a nanoparticle may be classified, for example, as a nanocapsule, vesicle, liposome, lipid nanoparticle, micelle, cross-linked micelle, lipoplex, a polyplex, a mixed or hybrid complex, to mention just a few of the possible designations for specific types of nanoparticles. A “lipid nanoparticle” (LNP) is a nanoparticle composed of lipids, typically including at least one amphiphilic membrane-forming lipid and, optionally, other lipids, and optionally further including a cargo material, such as a nucleic acid compound.As used herein, the term “lipid nanoparticles” or “LNP” includes any subtype and morphology of nanoparticles formed or co-formed by lipids, such as liposomes and lipoplexes. As defined above, lipid nanoparticles include any type of nanoparticle formed or coformed by lipids. In particular, lipid nanoparticles can be coformed by combinations of lipids comprising at least one amphi-like vesicle-forming lipid. Liposomes and lipoplexes are examples of lipid nanoparticles. In some embodiments, such lipid nanoparticles comprise a cationic lipid (e.g., a lipid of formula (I)) and one or more excipients selected from neutral lipids, charged lipids, spheroids, and polymer-conjugated lipids (e.g., a pegylated lipid such as a pegylated lipid of formula (II)). It is currently believed by the inventors that a composition comprising the cationic lipid as defined herein, a spheroid, a neutral lipid, and a polymer-conjugated lipid according to formula (II), at least in an aqueous environment, will typically exist as a composition comprising lipid nanoparticles that are formed from these excipients. An LNP may comprise any lipid capable of forming a particle to which one or more nucleic acid molecules are bound, or in which one or more nucleic acid molecules are encapsulated. In some embodiments, the mRNA, or a portion thereof, is encapsulated within the lipid portion of the lipid nanoparticle or within an aqueous space surrounded by part or all of the lipid portion of the lipid nanoparticle, thereby protecting it from enzymatic degradation or other undesirable effects induced by host organism or cellular mechanisms, e.g., an adverse immune response. In some embodiments, the mRNA, or a portion thereof, is associated with the lipid nanoparticles. As mentioned, a composition comprising the lipid excipients as described herein will typically form lipid nanoparticles, at least in an aqueous environment. As defined herein, nanoparticles are predominantly submicron in size. In certain embodiments, the mRNA, when present in the lipid nanoparticles, is resistant in aqueous solution to degradation by a nuclease. As used herein, the mean diameter may be represented by the z-average as determined by dynamic light scattering. In one embodiment, the composition is a sterile liquid composition comprising lipid nanoparticles having a mean hydrodynamic diameter (or mean size) as determined by dynamic laser scattering of about 30 nm to about 800 nm. In various embodiments, the lipid nanoparticles have a mean diameter of about 30 nm to about 150 nm, about 50 nm to about 200 nm,from approximately 60 nm to approximately 200 nm, from approximately 70 nm to approximately 200 nm, from approximately 80 nm to approximately 200 nm, from approximately 90 nm to approximately 200 nm, from approximately 90 nm to approximately 190 nm, from approximately 90 nm to approximately 180 nm, from approximately 90 nm to approximately 170 nm, from approximately 90 nm to approximately 160 nm, from approximately 90 nm to approximately 150 nm, from approximately 90 nm to approximately 140 nm, from approximately 90 nm to approximately 130 nm, from approximately 90 nm to approximately 120 nm, from approximately 90 nm to approximately 100 nm, from approximately 70 to approximately 90 nm, from approximately 80 nm to approximately 90 nm, from approximately 70 nm to approximately 80 nm, or from approximately 30 nm, 35 nm, 40 nm, 45 nm, 50nm, 55nm, 60nm, 65nm, 70nm, 75nm, 80nm, 85nm, 90nm, 95nm, 100nm, 105nm, 110nm, 115nm, 120nm, 125nm, 130nm, 135nm, 140nm,145 nm, 150 nm, 160 nm, 170 nm, 180 nm, 190 nm, or 200 nm, and are substantially nontoxic. In another preferred embodiment of the invention, the lipid nanoparticles have a hydrodynamic diameter in the range of about 50 nm to about 300 nm, or about 60 nm to about 250 nm, about 60 nm to about 150 nm, or about 60 nm to about 120 nm, or about 80 nm to about 160, or about 90 nm to about 140 nm, 50 nm to about 300 nm, or about 60 nm to about 250 nm, or about 60 nm to about 200 nm, or about 70 to 200 nm, or about 75 nm to about 160, or about 100 nm to about 140 nm, or about 90 nm to about 140 nm. Compositions comprising the lipid excipients as described herein that produce lipid nanoparticles of the invention may be relatively homogeneous. A polydispersity index (PDI) may be used to indicate the homogeneity of a composition. IVIA / a / ZUZZ / UU l oou nanoparticles, for example, the particle size distribution of nanoparticle compositions. A small polydispersity index (e.g., less than 0.3) generally indicates a narrow particle size distribution. A nanoparticle composition of the invention may have a polydispersity index of about 0 to about 0.35, such as 0.01, 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, 0.10, 0.11, 0.12, 0.13, 0.14, 0.15, 0.16, 0.17, 0.18, 0.19, 0.20, 0.21, 0.22, 0.23, 0.24, 0.25, 0.26, 0.27, 0.28, 0.29, 0.30, 0.31, 0.32, 0.33, 0.34, or 0.35. In some embodiments, the polydispersity index (PDI) of a nanoparticle composition may be about 0. Various optional features, selections, and preferences related to the composition of the invention in general have been described herein; all of these also apply to lipid nanoparticles, as will be readily understood by one skilled in the art. Similarly, the options and preferences apply to compositions comprising such lipid nanoparticles. For example, lipid nanoparticles according to one preferred embodiment comprise a cationic lipid as defined above, a neutral lipid which may be DphyPE, optionally in combination with a second neutral lipid which may be DHPC, a spheroid which may be cholesterol, and a polymer-conjugated lipid which may be 1,2-dimyristoyl-rac-glycero-3-methoxypolyethylene glycol (PEG-DMG); where the cationic lipid may optionally be selected from the compounds listed in Table 1. In the context of the present invention, the mRNA is thus preferably comprised in a liquid or semi-liquid composition, wherein the mRNA is complexed or associated with a lipid nanoparticle according to one of the preferred embodiments. That is, in a preferred embodiment, said liquid or semi-liquid composition comprises a complex, wherein the complex comprises the mRNA, wherein the complex is preferably present as a lipid nanoparticle as defined herein. With respect to the amounts of the respective excipients, it is preferred that the cationic lipid be incorporated into the lipid nanoparticles, or into the composition according to the invention, in a relatively high molar amount compared to the molar amount in which the polymer conjugated to the lipid is present. Furthermore, the molar amount of the cationic lipid is also preferably greater than the molar amount of the neutral lipid in the composition or in the nanoparticles, respectively. Furthermore, the molar amount of the steroid is optionally greater than the molar amount of the lipid conjugated to the polymer. In certain embodiments, the polymer-conjugated lipid is present in the LNP in an amount of about 1 mol % to about 10 mol %, relative to the total lipid content of the nanoparticle. In one embodiment, the polymer-conjugated lipid is present in the LNP in an amount of about 1 mol % to about 5 mol %. In one embodiment, the polymer-conjugated lipid is present in the LNP in about 1 mol % or about 1.5 mol %. In various embodiments, the molar ratio of the cationic lipid (e.g., lipid of formula (I)) to the polymer-conjugated lipid ranges from about 100:1 to about 25:1, from about 50:1 to about 25:1, or from about 40:1 to about 50:1. 25:1. In certain embodiments, the LNP comprises one or more additional lipids that stabilize particle formation during particle formation. Suitable stabilizing lipids include neutral lipids and anionic lipids. In various embodiments, the molar ratio of the cationic lipid (e.g., lipid of formula (I)) to the neutral lipid ranges from about 2:1 to about 8:1, from about 3:1 to about 7:1, or from about 4:1 to about 6:1. As used herein, references to molar amounts of lipid excipients in the composition of the invention should also be understood as a description of the molar amounts of the respective excipients in the lipid nanoparticles comprised in the composition, since lipid nanoparticles are typically formed from these excipients and reflect the same quantitative proportions of excipients as the overall composition containing the nanoparticles. In general, the amount of cationic lipid in the composition (and therefore in the lipid nanoparticles) is typically at least about 20 mol %, relative to the total molar amount of all lipid excipients in the composition (or nanoparticles). In another embodiment, the amount of cationic lipid is at least about 25 mol %, or at least 30 mol %, respectively.In other preferred embodiments, the amount of the cationic lipid in the compositions is from about 30 mol % to about 70 mol %, or from about 40 mol % to about 70 mol %, or from about 45 mol % to about 65 mol %, respectively; such as about 30, 35, 40, 45, 50, 55, 60, 65, or 70 mol %, or from about 40 mol % to about 60 mol %, respectively; such as about 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59 or 60 mol %, respectively. The amount of the steroid in the composition may optionally be at least 10 mol %, or may be in the range of 10 mol % to 60 mol %, or 20 mol % to 50 mol %, or 25 mol % to about 45 mol %, respectively; such as about 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, or 60 mol %, respectively. Again, for the avoidance of doubt, the mole percentages are relative to the total molar amount of all lipid excipients in the composition. The neutral lipid may optionally be present in an amount of at least about 5 mol %. In some embodiments, the amount of the neutral lipid in the composition is in the range of about 5 mol % to about 25 mol %, or about 5 mol % to about 15 mol %, or about 8 mol % to about 12 mol %, respectively; such as about 5 mol%, 6 mol%, 7 mol%, 8 mol%, 9 mol%, 10 mol%, 11 mol%, 12 mol%, 13 mol%, 14 mol%, 15 mol%, 16 mol%, 17 mol%, 18 mol%, 19 mol%, 20 mol%, 21 mol%, 22 mol%, 23 mol%, 24 mol%, or 25 mol%, respectively, using the same basis for the mole percentages. This amount is the amount of total neutral lipids, i.e., it may be the total amount resulting from the amounts of two neutral lipids, such as DPhyPE and DHPC. The amount of the polymer-conjugated lipid in the composition or in the lipid nanoparticles may be selected, for example, to be about 0.1 mol % and greater. In certain embodiments, the amount of polymer-conjugated lipid is in the range of about 0.5 mol % to about 5 mol %, or about 1 mol % to about 3 mol %, such as about 0.1, 0.3, 0.5, 1, 2, 3, 4, or 5 mol %, respectively, again using the total molar amount of all lipid excipients as the basis for the mole percentages. In certain other embodiments, the composition or the lipid nanoparticles may comprise 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2.0, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3.0, 3.1, 3.2, 3.3, 3.4, 3.5, 3.6, 3.7, 3.8, 3.9, 4.0, 4.1, 4.2, 4.3, 4.4, 4.5, 4.6, 4.7, 4.8, 4.9, 5.0, 5.1, 5.2, 5.3, 5.4, ​​5.5, 5.6, 5.7, 5.8, 5.9, 6, 6.1, 6.2, 6.3, 6.4, 6.5, 6.6, 6.7, 6.8, 6.9, 7 mol % or more than 7 mol % of polymer-conjugated lipid. In a preferred embodiment, the content of the polymer-conjugated lipid or pegylated lipid is about 1 to 5 mol % of the total lipid content of the formulation. As a non-limiting example, the lipid nanoparticle comprises 1.5% polymer-conjugated lipid. As another non-limiting example, the lipid nanoparticle comprises 1.7% polymer-conjugated lipid. As another non-limiting example, the lipid nanoparticle comprises 3% polymer-conjugated lipid. As another example, the lipid nanoparticle comprises 5% lipid conjugated with polymer. In one embodiment, the composition comprises lipid nanoparticles comprising: (a) the cationic lipid according to formula (I) or as described herein in an amount of 30-70 mol %; (b) the spheroid in an amount of 20-50 mol%; (c) the neutral lipid in an amount of 5-25 mol%; and (d) the polymer-conjugated lipid in an amount of 0.5-5 mol%; each quantity being relative to the total molar quantity of all the lipid excipients of the lipid nanoparticles. In another embodiment, the composition comprises lipid nanoparticles comprising: (a) the cationic lipid according to formula (I) or as described herein in an amount of 40-70 mol %; (b) the steroid in an amount of 20-50 mol%; (c) the neutral lipid in an amount of 5-15 mol%; and (d) the polymer-conjugated lipid in an amount of 0.5-5 mol%; each quantity being relative to the total molar quantity of all the lipid excipients of the lipid nanoparticles. In one embodiment, the composition comprises lipid nanoparticles comprising: (a) the cationic lipid according to formula (I) or as described herein in an amount of 20-60 mol %; (b) the steroid in an amount of 25-55 mol%; (c) the neutral lipid in an amount of 5-25 mol%; and (d) the polymer-conjugated lipid in an amount of 0.5-15 mol%; each quantity being relative to the total molar quantity of all the lipid excipients of the lipid nanoparticles. In another embodiment, the composition comprises lipid nanoparticles comprising: (a) the cationic lipid according to formula (I) or as described herein in an amount of 45-65 mol %; (b) the spheroid in an amount of 25-45 mol%; (c) the neutral lipid in an amount of 8-12 mol%; and (d) the polymer-conjugated lipid in an amount of 1-3 mol%; each quantity being relative to the total molar quantity of all the lipid excipients of the lipid nanoparticles. In another preferred embodiment, the composition comprises lipid nanoparticles comprising: (a) a cationic lipid according to formula (I) or as described herein in an amount of 45-65 mol %; (b) cholesterol in an amount of 25-45% by moles; (c) neutral lipid in an amount of 8-12 mol%; and (d) polymer-conjugated lipid in an amount of 1-3 mol%; each quantity being relative to the total molar quantity of all the lipid excipients of the lipid nanoparticles. In another preferred embodiment, the composition comprises lipid nanoparticles containing: (a) a cationic lipid according to formula (I) or as described herein in an amount of 45-65 mol %; (b) cholesterol in an amount of 25-45% by moles; (c) DPhyPE in an amount of 8-12 mol% and optionally DHPC in an amount of 1 to 10 mol%; and (d) polymer-conjugated lipid in an amount of 1-3 mol%. each quantity being relative to the total molar quantity of all the lipid excipients of the lipid nanoparticles. In another preferred embodiment, the composition comprises lipid nanoparticles containing: (a) a cationic lipid according to formula (I) or as described herein in an amount of 45-65 mol %; (b) cholesterol in an amount of 25-45% by moles; (c) DPhyPE in an amount of 8-12 mol % and optionally DHPC in an amount of 1 to 10 mol %; and (d) PEG-DMG 2000 in an amount of 1-3 mol %; each quantity being relative to the total molar quantity of all the lipid excipients of the lipid nanoparticles. In these embodiments, the cationic lipid is preferably a compound selected according to any of the preferences described herein. For example, the cationic lipid can be selected from the compounds listed in Table 1. In addition, these embodiments can also comprise a spheroid, a neutral lipid, and / or a polymer-conjugated lipid selected according to any of the preferences described herein. In all embodiments mentioning lipid compositions or nanoparticles as described herein and where mole % values ​​are given for each excipient, each amount should be viewed relative to the total molar amount of all lipid excipients in the lipid nanoparticles. In a further preferred embodiment, the composition or lipid nanoparticle as described herein comprises 59 mol% of cationic lipid according to formula (I) of the invention, 10 mol% of neutral lipid, 29.3 mol% of spheroid and 1.7 mol% of polymer-conjugated lipid. In one embodiment, the composition or lipid nanoparticles described herein comprise 59 mol % of cationic lipid according to formula (I) of the invention, 10 mol % of DPhyPE, 29.3 mol % of cholesterol and 1.7 mol % of DMG-PEG 2000. In one embodiment, the composition or lipid nanoparticles described herein comprise 59 mol % of cationic lipid according to formula (I) of the invention, 10 mol % of DPhyPE, 29.3 mol % of cholesterol and 1.7 mol % of C10-PEG 2000. In one embodiment, the composition or lipid nanoparticles described herein comprise 59 mol % of cationic lipid according to formula (I) of the invention, 10 mol % of DPhyPE, 29.3 mol% cholesterol and 1.7 mol% Cer8PEG 2000. In another embodiment, the composition or lipid nanoparticle as described herein comprises 47.4 mol% of cationic lipid according to formula (I) of the invention, 10 mol% of neutral lipid, 40.9 mol% of spheroid and 1.7 mol% of polymer-conjugated lipid. In a further embodiment, the composition or lipid nanoparticles described herein comprise 47.4 mol % of cationic lipid according to formula (I) of the invention, 10 mol % of DPhyPE, 40.9 mol % of cholesterol and 1.7 mol % of DMG-PEG 2000. In one embodiment, the composition or lipid nanoparticles described herein comprise 47.4 mol % of cationic lipid according to formula (I) of the invention, 10 mol % of DPhyPE, 40.9 mol % of cholesterol and 1.7 mol % of C10-PEG 2000. In one embodiment, the composition or lipid nanoparticles described herein comprise 47.4 mol % of cationic lipid according to formula (I) of the invention, 10 mol% of DPhyPE, 40.9 mol% of cholesterol and 1.7 mol% of Cer8-PEG 2000. In another embodiment, the composition or lipid nanoparticle as described herein comprises 59 mol% cationic lipid according to formula (I) of the invention, 11 mol% neutral lipid, 28.3 mol% steroid and 1.7 mol% polymer-conjugated lipid. MA / a / ¿U¿¿ / UU l oou In one embodiment, the lipid composition or nanoparticles described herein comprise 59 mol % cationic lipid according to formula (I) of the invention, 10 mol % DphyPE and 1 mol % DHPC, 28.3 mol % cholesterol and 1.7 mol % DMG-PEG 2000. In one embodiment, the lipid composition or nanoparticles described herein comprise 59 mol % cationic lipid according to formula (I) of the invention, 10 mol % DphyPE and 1 mol % DHPC, 28.3 mol % cholesterol and 1.7 mol % C10-PEG 2000. In one embodiment, the lipid composition or nanoparticles described herein comprise 59 mol % cationic lipid according to formula (I) of the invention, 10 mol% of DphyPE and 1 mol% of DHPC, 29.3 mol% of cholesterol and 1.7 mol% of Cer8-PEG 2000. In another embodiment, the composition or lipid nanoparticle as described herein comprises 49 mol% of cationic lipid according to formula (I) of the invention, 20 mol% of neutral lipid, 29.3 mol% of spheroid and 1.7 mol% of polymer-conjugated lipid. In one embodiment, the lipid composition or nanoparticles described herein comprise 49 mol % cationic lipid according to formula (I) of the invention, 10 mol % DphyPE and 10 mol % DHPC, 29.3 mol % cholesterol and 1.7 mol % DMG-PEG 2000. In one embodiment, the lipid composition or nanoparticles described herein comprise 49 mol % cationic lipid according to formula (I) of the invention, 10 mol % DphyPE and 10 mol % DHPC, 29.3 mol % cholesterol and 1.7 mol % C10-PEG 2000. In one embodiment, the lipid composition or nanoparticles described herein comprise 49 mol % moles of cationic lipid according to formula (I) of the invention, 10 mol% of DphyPE and 10 mol% of DHPC, 29.3 mol% of cholesterol and 1.7 mol% of Cer8-PEG 2000. In any of the previous embodiments in this section that describe specific compositions or lipid nanoparticles having different percentage values ​​for the excipients, if 1,2-diphytanoyl-sn-glycero-3-phosphoethanolamine (DPhyPE) is mentioned as the neutral lipid, in additional embodiments DPhyPE may be exchanged with another neutral lipid, preferably 1,2-diphytanoyl-sn-glycero-3-phosphocholine (DPhyPC). Furthermore, in any of the previous embodiments in this section describing specific compositions or lipid nanoparticles having different percentage values ​​for the excipients, if 1,2-diphytanoyl-sn-glycero-3-phosphoethanolamine (DPhyPE) is mentioned as the neutral lipid, in even further embodiments DPhyPE may be exchanged with another neutral lipid, preferably 1,2-dioleoylsn-glycero-3-phosphocholine (DOPC; also referred to as dioleoylphosphatidylcholine) or alternatively 1,2-dioleoylsn-glycero-3-phosphoethanolamine (DOPE). Other preferred lipid compositions according to additional specific embodiments of the present invention comprise at least four lipid excipients as described herein in Table E. For example, a preferred lipid composition comprises the excipients as described in the line Έ1″ which are “C1″ as the cationic lipid (as described herein in Table 1), DPhyPE as the neutral lipid, cholesterol as the sterol, and DMG-PEG 2000 as the polymer-conjugated lipid excipient. As another example, a preferred lipid composition comprises the excipients as described in the line Έ35″, which are “C12″ as the cationic lipid (as described herein in Table 1), DPhyPE as the neutral lipid, cholesterol as the sterol, and C10-PEG 2000 as the polymer-conjugated lipid excipient. Table E: Lipid excipient combinations for preferred compositions of the invention (Chol = Cholesterol; DMG-PEG2K = DMG-PEG 2000; Cio-PEG2K = C10-PEG 2000; Cer8-PEG2K = Cer8-PEG 2000; table divided into two tabs) l oou Combinación de excipientes [designación] Lípido catiónico Esterol Lípido neutro Lípido conjugado con polímero E1 C1 Chol DPhyPE DMG- PEG2K E2 C2 Chol DPhyPE DMG- PEG2K E3 C3 Chol DPhyPE DMG- PEG2K E4 C4 Chol DPhyPE DMG- PEG2K E5 C5 Chol DPhyPE DMG- PEG2K E6 C6 Chol DPhyPE DMG- PEG2K E7 C7 Chol DPhyPE DMG- PEG2K E8 C8 Chol DPhyPE DMG- PEG2K E9 C9 Chol DPhyPE DMG- PEG2K E10 C10 Chol DPhyPE DMG- PEG2K E11 C11 Chol DPhyPE DMG- PEG2K E12 C12 Chol DPhyPE DMG- PEG2K E13 C13 Chol DPhyPE DMG- PEG2K E14 C14 Chol DPhyPE DMG- PEG2K E15 C15 Chol DPhyPE DMG- PEG2K E16 C16 Chol DPhyPE DMG- PEG2K E17 C17 Chol DPhyPE DMG- PEG2K E18 C18 Chol DPhyPE DMG- PEG2K E19 C19 Chol DPhyPE DMG- PEG2K E20 C20 Chol DPhyPE DMG- PEG2K E21 C21 Chol DPhyPE DMG- PEG2K E22 C22 Chol DPhyPE DMG- Combinación de excipientes [designación] Lípido catiónico Esterol Lípido neutro Lípido conjugado con polímero E36 C13 Chol DPhyPE Cw-PEG2K E37 C14 Chol DPhyPE Cio-PEG2K E38 C15 Chol DPhyPE CW-PEG2K E39 C16 Chol DPhyPE CW-PEG2K E40 C17 Chol DPhyPE CW-PEG2K E41 C18 Chol DPhyPE CW-PEG2K E42 C19 Chol DPhyPE Cio-PEG2K E43 C20 Chol DPhyPE CW-PEG2K E44 C21 Chol DPhyPE CW-PEG2K E45 C22 Chol DPhyPE CW-PEG2K E46 C23 Chol DPhyPE CW-PEG2K E47 C1 Chol DPhyPE Cer8- PEG2K E48 C2 Chol DPhyPE Cer8- PEG2K E49 C3 Chol DPhyPE Cer8- PEG2K E50 C4 Chol DPhyPE Cer8- PEG2K E51 C5 Chol DPhyPE Cer8- PEG2K E52 C6 Chol DPhyPE Cer8- PEG2K E53 C7 Chol DPhyPE Cer8- PEG2K E54 C8 Chol DPhyPE Cer8- PEG2K E55 C9 Chol DPhyPE Cer8- PEG2K E56 C10 Chol DPhyPE Cer8- PEG2K E57 C11 Chol DPhyPE Cer8- PEG2K E23 C23 Chol DPhyPE DMG- PEG2K E24 C1 Chol DPhyPE Cw-PEG2K E25 C2 Chol DPhyPE Cio-PEG2K E26 C3 Chol DPhyPE Cio-PEG2K E27 C4 Chol DPhyPE Cw-PEG2K E28 C5 Chol DPhyPE CW-PEG2K E29 C6 Chol DPhyPE Cio-PEG2K E30 C7 Chol DPhyPE Cio-PEG2K E31 C8 Chol DPhyPE Cio-PEG2K E32 C9 Chol DPhyPE Cw-PEG2K E33 C10 Chol DPhyPE CW-PEG2K E34 C11 Chol DPhyPE Cio-PEG2K E35 C12 Chol DPhyPE C10-PEG2K PEG2K E58 C12 Chol DPhyPE Cer8- PEG2K E59 C13 Chol DPhyPE Cer8- PEG2K E60 C14 Chol DPhyPE Cer8- PEG2K E61 C15 Chol DPhyPE Cer8- PEG2K E62 C16 Chol DPhyPE Cer8- PEG2K E63 C17 Chol DPhyPE Cer8- PEG2K E64 C18 Chol DPhyPE Cer8- PEG2K E65 C19 Chol DPhyPE Cer8- PEG2K E66 C20 Chol DPhyPE Cer8- PEG2K E67 C21 Chol DPhyPE Cer8- PEG2K E68 C22 Chol DPhyPE Cer8- PEG2K E69 C23 Chol DPhyPE Cer8- PEG2K Excipeent combination [designation] Cationic lipid Sterol Neutral lipid Polymer-conjugated lipid E70 C24 Chol DPhyPE DMG-PEG2K E71 C25 Chol DPhyPE DMG-PEG2K E72 C26 Chol DPhyPE DMG-PEG2K E73 C27 Chol DPhyPE DMG-PEG2K E74 C24 Chol DPhyPE Cio-PEG2K E75 C25 Chol DPhyPE Cio-PEG2K E76 C26 Chol DPhyPE Cw-PEG2K E77 C27 Chol DPhyPE Cio-PEG2K E78 C24 Chol DPhyPE Cer8-PEG2K E79 C25 Chol DPhyPE Cer8-PEG2K E80 C26 Chol DPhyPE Cer8-PEG2K E81 C27 Chol DPhyPE Cer8-PEG2K E82 C1 Chol DphyPE+DHPC DMG-PEG2K o C10-PEG2K o Cer8-PEG2K E83 C2 Chol DphyPE+DHPC DMG-PEG2K o C10-PEG2K o Cer8-PEG2K E84 C3 Chol DphyPE+DHPC DMG-PEG2K or Cio- PEG2K o Cer8-PEG2K E85 04 Chol DphyPE+DHPC DMG-PEG2K o C10- PEG2K o Cer8-PEG2K E86 05 Chol DphyPE+DHPC DMG-PEG2K o C10- PEG2K o Cer8-PEG2K E87 C6 Chol DphyPE+DHPC DMG-PEG2K o C10- PEG2K o Cer8-PEG2K E88 C7 Chol DphyPE+DHPC DMG-PEG2K o C10- PEG2K o Cer8-PEG2K E89 08 Chol DphyPE+DHPC DMG-PEG2K o C10- PEG2K o Cer8-PEG2K E90 09 Chol DphyPE+DHPC DMG-PEG2K o C10- PEG2K o Cer8-PEG2K E91 C10 Chol DphyPE+DHPC DMG-PEG2K o C10- PEG2K o Cer8-PEG2K E92 011 Chol DphyPE+DHPC DMG-PEG2K o C10- PEG2K o Cer8-PEG2K E93 012 Chol DphyPE+DHPC DMG-PEG2K o C10- PEG2K o Cer8-PEG2K E94 013 Chol DphyPE+DHPC DMG-PEG2K o C10- PEG2K o Cer8-PEG2K E95 014 Chol DphyPE+DHPC DMG-PEG2K o C10- PEG2K o Cer8-PEG2K E96 015 Chol DphyPE+DHPC DMG-PEG2K o C10- PEG2K o Cer8-PEG2K E97 C16 Chol DphyPE+DHPC DMG-PEG2K o Cw- PEG2K o Cer8-PEG2K E98 017 Chol DphyPE+DHPC DMG-PEG2K o C10- PEG2K o Cer8-PEG2K E99 018 Chol DphyPE+DHPC DMG-PEG2K o C10- PEG2K o Cer8-PEG2K E100 019 Chol DphyPE+DHPC DMG-PEG2K o C10- PEG2K o Cer8-PEG2K E101 020Chol DphyPE+DHPC DMG-PEG2K or C10- PEG2K or Cer8-PEG2K E102 C21 Chol DphyPE+DHPC DMG-PEG2K or C10- PEG2K or Cer8-PEG2K E103 022 Chol DphyPE+DHPC DMG-PEG2K or C10- PEG2K or Cer8-PEG2K E104 023 Chol DphyPE+DHPC DMG-PEG2K or C10- PEG2K or Cer8-PEG2K E105 024 Chol DphyPE+DHPC DMG-PEG2K or C10- PEG2K or Cer8-PEG2K E106 025 Chol DphyPE+DHPC DMG-PEG2K or C10- PEG2K or Cer8-PEG2K E107 C26 Chol DphyPE+DHPC DMG-PEG2K or C10- PEG2K or Cer8-PEG2K E108 C27 Chol DphyPE+DHPC DMG-PEG2K or C10- PEG2K or Cer8-PEG2K Furthermore, preferred lipid formulations of the invention showing different mole percentages of the at least four lipid excipients of the inventive compositions are shown in Table F. For example, a preferred lipid composition comprises the mole percentages of lipids IVIA / S / ZUZZ / UU / oou as disclosed in line “F1”, i.e., 59 mol % cationic lipid, 29.3 mol % sterol, 10 mol % neutron lipid, and 1.7 mol % polymer-conjugated lipid. As another example, a preferred lipid composition comprises the mole percentages of the lipids as disclosed in line “F31”, i.e., 45 mol % cationic lipid, 43.5 mol % sterol, 10 mol % neutron lipid, and 1.5 mol % polymer-conjugated lipid. ynaal / a / zuzz / uu / oou Table F: Formulations including molar percentages for excipients of preferred compositions of the invention (table divided into two formulators) Formulation [designation] Cationic lipid [mol%] steral [mol% olese] Neutral lipid [mol% polymer-conjugated lipid [mol% sum [mol% F1 59 29.3 10 1.7 100 F2 59 34.3 5 1.7 100 F3 59 34.5 5 1.5 100 F4 59 29.5 10 1.5 100 F5 59 31 10 0 100 F6 59 24.3 15 1.7 100 F7 59 24.5 15 1.5 100 F8 59 26 15 0 100 F9 59 19.3 20 1.7 100 F10 59 19.5 20 1.5 100 F11 59 21 20 0 100 F12 47.4 45.9 5 1.7 100 F13 47.4 46.1 5 1.5 100 F14 47.4 40.9 10 1.7 100 F15 47.4 41.1 10 1.5 100 F16 47.4 42.6 10 0 100 F17 47.4 35.9 15 1.7 100 F18 47.4 36.1 15 1.5 100 F19 47.4 37.6 15 0 100 F20 47.4 30.9 20 1.7 100 F21 47.4 31.1 20 1.5 100 F22 47.4 32.6 20 0 100 F23 40 53.5 5 1.5 100 F24 40 48.5 10 1.5 100 F25 40 50 10 0 100 F26 40 43.5 15 1.5 100 F27 40 45 15 0 100 Formulation [designation] Cationic lipid [mol% ester [mol% neutral lipid [mol% polymer-conjugated lipid [mol% sum [mol% F31 45 43.5 10 1.5 100 F32 45 45 10 0 100 F33 45 38.5 15 1.5 100 F34 45 40 15 0 100 F35 45 33.5 20 1.5 100 F36 45 35 20 0 100 F37 50 43.5 5 1.5 100 F38 50 38.5 10 1.5 100 F39 50 40 10 0 100 F40 50 33.5 15 1.5 100 F41 50 35 15 0 100 F42 50 28.5 20 1.5 100 F43 50 30 20 0 100 F44 55 38.5 5 1.5 100 F45 55 33.5 10 1.5 100 F46 55 35 10 0 100 F47 55 28.5 15 1.5 100 F48 55 30 15 0 100 F49 55 23.5 20 1.5 100 F50 55 25 20 0 100 F51 60 33.5 5 1.5 100 F52 60 28.5 10 1.5 100 F53 60 30 10 0 100 F54 60 23.5 15 1.5 100 F55 60 25 15 0 100 F56 60 18.5 20 1.5 100 F57 30- 5-25 20- 0.5-5 ** F28 40 38.5 20 1.5 100 F29 40 40 20 0 100 F30 45 48.5 5 1.5 100 F61 59 28.3 11 1.7 100 70 50 F58 40- 70 5-15 20- 50 0.5-5 ** F59 20- 60 5-25 25- 55 0.5-15 ** F60 45- 65 8-12 25- 45 1-3 ** F62 49 29.3 20 1.7 100 “self-evidently, the sum [% by moles of the last four formulations in Table F, F57, F58, F59 and F60, is defined to be 100% by moles. That is, one skilled in the art is naturally able to select a value from the given ranges of the four excipients, such that the mole percentage for each excipient of the preferred compositions of the invention sums to 100%. Accordingly, in a more preferred embodiment of the invention, a composition of the invention comprises excipients as disclosed in Table E selected from the group consisting of Excipient combination designation. E1, E2, E3, E4, E5, E6, E7, E8, E9, E10, E11, E12, E13, E14, E15, E16, E17, E18, E19, E20, E21, E22, E23, E24, E25, E26, E27, E28, E29, E30, E31, E32, E33, E34, E35, E36, E37, E38, E39, E40, E41, E42, E43, E44, E45, E46, E47, E48, E49, E50, E51, E52, E53, E54, E55, E56, E57, E58, E59, E60, E61, E62, E63, E64, E65, E66, E67, E68, E69, E70, E71, E72, E73, E74, E75, E76, E77, E78, E79, E80, E81, E82, E83, E84, E85, E86, E87, E88, E89, E90, E91, E92, E93, E94, E95, E96, E97, E98, E99, E100, E101, E102, E103, E104, E105, E106, E107 and E108; en percentages en moles distintos como se divulga en laTable F selecciones del grupo que consiste en desginación de formulation F1, F2, F3, F4, F5, F6, F7, F8, F9, F10, F11, F12, F13, F14, F15, F16, F17, F18,F19, F20, F21, F22, F23, F24, F25, F26, F27, F28, F29, F30, F31, F32, F33, F34, F35, F36, F37, F38,F39, F40, F41, F42, F43, F44, F45, F46, F47, F48, F49, F50, F51, F52, F53, F54, F55, F56, F57, F58,F59, F60, F61 and F62. A particularly preferred embodiment for a lipid nanoparticle of the present invention is when the F1xE23 combination according to Table E and Table F is used to formulate a lipid nanoparticle, i.e. 59 mol % C23 cationic lipid as described in Table 1, i.e. COATSOME® SS-EC (former name: SS-33 / 4PE-15 as seen in the examples section; NOF Corporation, Tokyo, Japan), 29.3 mol % cholesterol as steroid, 10 mol % DPhyPE as neutral lipid / phospholipid and 1.7 mol % DMG-PEG 2000 as polymer conjugated lipid. Such an LNP composition is referred to herein and in the working examples as “GN01”. SS-EC has a positive charge at pH 4 and a neutral charge at pH 7, which is advantageous for the LNPs and formulations / compositions of the present invention.For “GN01”, N / P (mole ratio of lipid to mRNA) is preferably 14 and the total lipid / mRNA mass ratio is preferably between about 20 and about 60, more preferably between about 30 and about 50 and most preferably is 40 (m / m). A further particularly preferred embodiment for a lipid nanoparticle of the present invention is when the F1xE2 combination according to Table E and Table F is used to formulate a lipid nanoparticle, i.e. 59 mol % of lipid 02 as described in Table 1 as cationic lipid (i.e. HEXA-C5DE-PipSS as follows from the examples section, Figure 1B), 29.3 mol % cholesterol as steroid, 10 mol % DPhyPE as neutral lipid / phospholipid and 1.7 mol % DMG-PEG 2000 as polymer conjugated lipid. Such an LNP composition is referred to herein and in the working examples as “GN02”. For “GN02”, N / P (mole ratio of lipids to mRNA) is preferably 17.5 and the total mass ratio of lipids / mRNA is preferably between 20 and 60, more preferably between 30 and 50 and most preferably 40 (m / m). Another particularly preferred embodiment for a lipid nanoparticle of the present invention is when the F1xE23 combination according to Table E and Table F is used to formulate a lipid nanoparticle, i.e. 59 mol % C23 cationic lipid as described in Table 1, i.e. COATSOME® SS-EC (former name: SS-33 / 4PE-15 as seen in the examples section; NOF Corporation, Tokyo, Japan), 26 mol % cholesterol as steroid, 10 mol % DPhyPE as neutral lipid / phospholipid and 5 mol % Cer8 as polymer conjugated lipid comprising shorter alkyl chains. Such an LNP composition is referred to herein and in the working examples as “GN01-C8”.For “GN01-C8”, N / P (molar ratio of lipids to mRNA) is preferably 14 and the total mass ratio of lipids / mRNA is preferably between about 20 and about 60, more preferably between about 30 and about 50 and most preferably 40 (m / m). A further particularly preferred embodiment for a lipid nanoparticle of the present invention is when the F1xE72 combination according to Table E and Table F is used to formulate a lipid nanoparticle, i.e. 59 mol % C26 lipid as described in Table 1 as cationic lipid (i.e. THIOETHER as follows from the examples section, Figure 25A), 29.3 mol % cholesterol as steroid, 10 mol % DPhyPE as neutral lipid / phospholipid and 1.7 mol % DMG-PEG 2000 as polymer conjugated lipid. Such an LNP composition is referred to herein and in the working examples as “LNP28”. For “LNP28”, N / P (molar ratio of lipids to mRNA) is preferably 14 and the total mass ratio of lipids / mRNA is preferably between about 20 and about 60, more preferably between about 30 and about 50 and most preferably 40 (m / m). Furthermore, for a preferred composition, (i) the cationic lipid may be selected from the compounds in Table 1; and / or the (i) neutral lipid of neutral phospholipid is a zwitterionic compound selected from the group consisting of 1,2-diphytanoyl-sn-glycero-3-phosphoethanolamine (DPhyPE; also referred to as 1,2-di-(3,7,11,15-tetramethylhexadecanoyl)-sn-glycero-3-phosphoethanolamine), 1,2-diphytanoyl-sn-glycero-3-phosphocholine (DPhyPC), 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC; also known as dioleoylphosphatidylcholine), 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC, also known as dipalmitoylphosphatidylcholine), 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), phosphatidylethanolamines, distearoylphosphatidylcholines, dioleoyl-phosphatidylethanolamine (DOPEA), 1,2-distearol-sn-glycero-3-phosphoethanolamine (DSPE), palmitoyloleoyl osphatidylcholine (POPO), palmitoyloleoyl-phosphatidylethanolamine (POPE), 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE),dioleoyl 87 phosphatidylethanolamine 4-(N-maleimidomethyl)-cyclohexane-1-carboxylate (DOPE-mal), 1,2-dimyristoyl-sn-glycero-3β-phosphoethanolamine (DMPE), dipalmitoyl phosphatidyl ethanolamine (DPPE), dimyristoylphosphoethanolamine (DMPE), 1,2-dilinoleoyl-sn-glycero-3-phosphoethanolamine (DLoPE), distearoyl-phosphatidylethanolamine (DSPE), 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (POPE), 1,2-d¡lauroyl-sn-glycero-3-phosphoethanolamine (DLPE), 16-O-monomethylphosphoethanolamine, 16O-dimethylphosphatidylethanolamine, 1,2-dierucoyl-sn-glycero-3-phosphoethanolamine (DEPE), 18-1-trans phosphatidylethanolamine, 1-stearo¡l-2-oleo¡lphosphat¡dethanolamine (SOPE), 1,2-Disqualeoyl-sngglycero-3-phosphoethanolamine (DSQPE), 1,2-dielaidoyl-sn- glycero-3-phosphoethanolamine (transDOPE), 1-Stearoyl-2l¡noleo¡l-sn-glycero-3-phosphoethanolamine (SLPE), 1-tr¡decanoyl-sn-glycero-3-phospho-L-serine (sodium salt), 1oleo¡l-2-h¡drox¡-sn-glycero-3-phospho-L-ser¡na (sodium salt),1-palm-2-oleoyl-sn-glycero-3-phospho-L-serine (sodium salt) (POPS), 1 -1-stearoyl-2-oleoyl-sn-glycero-3-phospho-L-serine (sodium salt), 1,2-dioleoyl-sn-glycero-3-phospho-L-serine (sodium salt) (DOPS), 1,2-diestearoyl-sn-glycero-3-phospho-L-serine (sodium salt), 1,2-diphytanoyl-sn-glycero-3-phospho-L-serine (sodium salt), 1-O-hexadecanyl-2-O-(9Z-octadecenyl)-sn-glycero-3-phosphoethanolamine, 1,2-diestearoyl-sn-glycero-3-phosphatidylcholine or 1,2-diestearoyl-sn-glycero-3-phosphocholine (DSPC), 1,2-di-O-phytanylsn-glycero-3-phosphoethanolamine, 1-palmitoyl-2-cholesteryl-ihemisuccinoyl- sn-glycero-3-phosphocholine (PChemsPC), 1,2-diclesterylhemsuccinoyl-sn-glycero-3-phosphocholine (DChemsPC), 2-((2,3bis(oleoloxypropyl)dmethylammonium)ethyl hydrogen phosphate (DOCP), 2-((2,3b¡s(oleo¡loxi)prop¡l)d¡mte¡lamon¡o)ethyleth¡lo (DOCPe) and 1 -0-octadecyl-2-0-methyl-sn-gl¡cero-3-phosphocol¡na (Edelfosine); optionally combined with 1,2-diheptanoyl-sn-glycero-3-phosphocholine (DHPC); y / o (iii) the polymer-conjugated lipid can be selected from the group that consists of a pegylated diacylglycerol lipid (PEG-DAG); a PEG-Cer lipid (PEG-Cer); a pegylated phosphatidylethanolamine lipid (PEG-PE); a pegylated diacylglycerol succinate lipid (PEG-S-DAG); a pegylated dialkoxypropyl carbamate lipid; 1,2-d¡mir¡sto¡l-rac-gl¡cero-3-metox¡poliet¡lengl¡col (“PEG-DMG” or “DMG-PEG”); 1,2-dicapril-rac-glycero-3-methylpoIoxyethyleneglycoI (PEG de diacylglycerol C10); N-octanoylesf ingosine-1-succinyl[methoxy(polyethylene glycol)] (PEG-Ceramida8 or PEG-Cer8); 4-O-(2',3'd¡(tetradecan¡lox¡)prop¡l-1Ό-(ω-methox¡(pol¡ethox¡)et¡l)butanod¡oate (PEG-S-DMG); 2-mPEG2000-n,n ditetradecylacetamida; N- [(methoxypoly(ethylene glycol)2000)carbamyl]-1,2-dimyristyloxypropyl-3-amine (PEG-c-DMA); 2,3-di(tetradecanox¡)prop¡lN-(cumetoxi(polietoxi)et¡l)carb amate., Alternatively, the composition may be provided in solid form. In particular, it may be provided as a sterile solid composition for reconstitution with a sterile liquid vehicle; in this case, the solid composition may further comprise one or more inactive ingredients selected from pH-modifying agents, bulking agents, stabilizers, nonionic surfactants, and antioxidants. In this embodiment, the sterile liquid vehicle is preferably an aqueous vehicle. The zeta potential of a nanoparticle composition can be used to indicate the electrokinetic potential of the composition. For example, the zeta potential can describe the surface charge of a nanoparticle composition. Lipid nanoparticles according to the invention may, due to the presence of both positively and negatively charged compounds, exhibit a relatively neutral zeta potential. The zeta potential (sometimes abbreviated as “charge”) can be determined together with the particle size of the particles, for example, by dynamic light scattering and laser Doppler microelectrophoresis, for example, using a Malvern Zetasizer Nano (Malvern Instruments Ltd.; Malvern, UK). Depending on the amount and nature of the charged compounds on the lipid nanoparticles, the nanoparticles can be characterized by a zeta potential. In a preferred embodiment,the zeta potential is in the range of about -50 mV to about +50 mV. In other preferred embodiments, the zeta potential is in the range of about -25 mV to about +25 mV. In some embodiments, the zeta potential of a lipid nanoparticle of the invention may be from about -10 mV to about +20 mV, from about -10 mV to about +15 mV, from about -10 mV to about +10 mV, from about -10 mV to about +5 mV, from about -10 mV to about 0 mV, from about -10 mV to about 5 mV, from about -5 mV to about +20 mV, from about -5 mV to about +15 mV, from about -5 mV to about +10 mV, from about -5 mV to about +5 mV, from about -5 mV to about 0 mV, from about 0 mV to about +20 mV, from about 0 mV to about +15 mV, from about 0 mV to about +10 mV,from about 0 mV to about +5 mV, from about +5 mV to about +20 mV, from about +5 mV to about +15 mV, or from about +5 mV to about +10 mV., In certain embodiments, the LNP comprises one or more targeting moieties capable of directing the LNP to a cell or cell population. For example, in one embodiment, the targeting moiety is a ligand that directs the LNP to a receptor located on the surface of a cell. In certain embodiments, the LNP comprises one or more internalization domains. For example, in one embodiment, the LNP comprises one or more domains that bind to a cell to induce internalization of the LNP. For example, in one embodiment, one or more internalization domains bind to a receptor found on a cell surface to induce receptor-mediated uptake of LNP. In certain embodiments, the LNP is capable of binding to a biomolecule in vivo, where the LNP-bound biomolecule can be recognized by a cell surface receptor to induce internalization. For example, in one embodiment, the LNP binds to systemic ApoE, leading to uptake of the LNP and associated cargo. In certain embodiments of the invention, the ApoE can be supplemented with the medium or pharmaceutical composition used. Preferably, in one embodiment, the compositions of the invention further comprise a biologically active ingredient. Biologically active ingredients As used herein, a biologically active ingredient means any compound or material that has a biological activity due to which the compound or material is potentially useful for the prevention, management, amelioration, treatment or therapy of a disease or condition in a subject, such as an animal, and in particular in a human subject. In one preferred embodiment, the active ingredient is a nucleic acid compound. Examples of nucleic acid compounds that are potentially useful for carrying out the invention include nucleic acid compounds selected from the group consisting of chemically modified or unmodified messenger RNA (mRNA), chemically modified or unmodified RNA, single-stranded or double-stranded RNA, coding or non-coding RNA, viral RNA, replicon RNA, and self-replicating RNA, or any combination thereof; preferably where the biologically active ingredient is an mRNA. In preferred embodiments, the nucleic acid compound complexes or associates with one or more lipids (e.g., cationic lipids and / or neutral lipids), thereby forming liposomes, lipid nanoparticles (LNPs), lipoplexes, and / or nanoliposomes. In this context, the terms “complexed” or “associated” refer to the essentially stable combination of the nucleic acid compound of the first aspect with one or more lipids in larger complexes or assemblies without covalent bonding. In specific embodiments, the active ingredient may include a CRISPR RNA (crRNA) plus a tracer RNA (tracrRNA), a guide RNA (gRNA), or a single guide RNA (gRNA), and / or a donor DNA together with a CRISPR endonuclease. Suitably, the CRISPR endonuclease may be provided as a protein or polypeptide or as an mRNA encoding said CRISPR endonuclease. A composition or formulation comprising this combination is suitable for delivering a CRISPR gene editing activity to a target cell. In one embodiment, compositions according to the invention may provide the gRNA and the mRNA encoding a CRISPR endonuclease, for separate, sequential, or simultaneous administration. That is, the gRNA and the mRNA may be provided within the same formulation or lipid nanoparticle according to the invention or may be provided in separate lipid nanoparticles for separate, simultaneous, or sequential administration.Suitably, the ratio of gRNA to mRNA for delivery is 1:1, 1:3, 1:9, 1:19, for example (i.e., 50%, 25%, 10%, and 5% guide RNA). In one embodiment, a gRNA and an mRNA encoding a CRISPR endonuclease such as cas9 are co-loaded into a formulation according to the invention. Advantageously, co-loading allows for improved encapsulation efficiency (EE) to be obtained. Suitably, a formulation or pharmaceutical composition according to the invention wherein gRNA and mRNA are co-loaded comprises LNPs with an average diameter of between 80 and 160 nm. In one embodiment, the gRNA may be a modified gRNA sequence. Suitable modifications are described, for example, in WO2016 / 089433 and PCT / GB2016 / 053312. Other suitable modifications will be familiar to those skilled in the art. By “CRISPR endonuclease” is meant an endonuclease that can be used in a CRISPR gene editing composition. Suitable “CRISPR endonucleases” include cas9 and its mutants and modified forms. Accordingly, the mRNA for use in combination with a gRNA is one encoding a CRISPR endonuclease, preferably cas9. Other “CRISPR endonucleases” include cpf1, for example. Those skilled in the art will recognize that a gRNA pairs with a particular “CRISPR endonuclease.” Accordingly, the invention contemplates a composition using a suitable gRNA / endonuclease pairing. Suitably, a gRNA is specific for a target gene, preferably wherein the target gene is a gene associated with liver disease. MA / a / ¿U¿¿ / UU l oou In another embodiment, the peptide or protein expressed by the nucleic acid compound is a therapeutic protein, or a fragment or variant thereof, wherein the therapeutic protein is beneficial for the treatment or prophylaxis of any hereditary or acquired disease or that improves the condition of an individual. In particular, therapeutic proteins play a key role in the design of new therapeutic agents that could modify and repair genetic deficiencies, destroy cancer cells or cells infected by pathogens, treat or prevent immune system disorders, or treat or prevent metabolic or endocrine disorders, among other functions. In another embodiment, the peptide or protein expressed by the nucleic acid compound is an antigen. As defined in more detail herein above, an antigen is a compound or material that can be recognized by the immune system, preferably the adaptive immune system, to trigger an antigen-specific immune response. In some embodiments, the active ingredient is siRNA. siRNAs are small interfering RNAs as, for example, described in international patent application PCT / EP03 / 08666. These molecules typically consist of a double-stranded RNA structure comprising between 15 and 25, preferably 18 to 23 pairs of nucleotides that are capable of pairing with each other, i.e., are essentially complementary to each other, typically mediated by Watson-Crick base pairing. One strand of this double-stranded RNA molecule is essentially complementary to a target nucleic acid, preferably an mRNA, while the second strand of said double-stranded RNA molecule is essentially identical to a stretch of said target nucleic acid. The siRNA molecule may be flanked on each side and each stretch, respectively, by a number of additional nucleotides which, however, In some embodiments, the active ingredient is RNAi. RNAi has essentially the same design as siRNA, however, the molecules are significantly longer compared to siRNA. RNAi molecules typically comprise 50 or more nucleotides and base pairs, respectively. In some embodiments, the active ingredient is an antisense nucleic acid. Antisense nucleic acids, as preferably used herein, are oligonucleotides that hybridize based on base complementarity to a target RNA, preferably mRNA, thereby activating RNaseH. RNaseH is activated by both phosphodiester- and phosphothioate-coupled DNA. However, phosphodiester-coupled DNA is rapidly degraded by cellular nucleases, whereas phosphothioate-coupled DNA is not. Therefore, antisense polynucleotides are effective only as DNA-RNA hybrid complexes. Preferred lengths of antisense nucleic acids range from 16 to 23 nucleotides. Examples of such antisense oligonucleotides are described, among others, in U.S. Patent 5,849,902 and U.S. Patent 5,989,912. In some embodiments, the active ingredient is a ribozyme. Ribozymes are catalytically active nucleic acids, preferably consisting of RNA, which essentially comprises two moieties. The first moiety exhibits catalytic activity, while the second moiety is responsible for the specific interaction with the target nucleic acid. Upon interaction between the target nucleic acid and said ribozyme moiety, typically by hybridization and Watson-Crick base pairing, MA / a / ¿U¿¿ / UU l oou essentially complementary base stretches on the two hybridizing strands, the catalytically active moiety may become active, meaning that it cleaves, either intramolecularly or intermolecularly, the target nucleic acid in case the catalytic activity of the ribozyme is a phosphodiesterase activity. Ribozymes, the principles of use and design are known to those skilled in the art and, for example, described in Doherty and Doudna {Annu. Rei. Biophys. Biomolstruct. 2000; 30: 457-75). In some embodiments, the active ingredient is an aptamer. Aptamers are nucleic acids D that are single- or double-stranded and that specifically interact with a target molecule. The manufacture or selection of aptamers is described, for example, in European patent EP 0 533 838. In contrast to RNAi, siRNA, antisense nucleotides, and ribozymes, aptamers do not degrade any target mRNA but instead specifically interact with the secondary and tertian structure of a target compound such as a protein. Upon interaction with the target, the target typically exhibits a change in its biological activity. The length of aptamers typically ranges from as little as 15 to 80 nucleotides, and preferably ranges from about 20 to about 50 nucleotides. In some embodiments, the active ingredient is a spiegelmer. Spiegelmers are described, for example, in international patent application WO 98 / 08856. Spiegelmers are aptamer-like molecules. However, spiegelmers consist entirely or mostly of L-nucleotides instead of D-nucleotides, in contrast to aptamers. Otherwise, particularly with respect to the possible lengths of the spiegelmers, the same applies to spiegelmers as described in connection with aptamers. mRNA In one preferred embodiment, the nucleic acid compound is an mRNA or an mRNA compound. As the inventors have discovered, the lipids and compositions according to the present invention are particularly well-suited for the in vivo administration of mRNA compounds expressing antigens and thus allow for highly effective, potent, versatile, and safe vaccines that can be rapidly developed at a reasonable cost. The specific antigens of interest for carrying out the present invention are described in more detail below. The mRNA compound according to the invention is encapsulated or associated with a lipid nanoparticle. The advantages of mRNA encoding at least one antigenic peptide or protein contained in lipid nanoparticles (LNP) are: Induction of a strong humoral immune response Induction of B cell memory Faster onset of immune protection Longevity of induced immune responses Induction of broad cellular T cell responses Induction of a proinflammatory environment (local and transient) Without induction of systemic cytokine or chemokine response i oou Good tolerability, no side effects, non-toxic Advantageous stability characteristics Formulation compatible with many different antigens: larger antigen cocktails feasible based on the same (production) technology Without vector immunity, that is, the technology can be used to vaccinate the same subject multiple times against multiple (different) antigens Speed, adaptability, simplicity and scalability of production. In certain embodiments, the lipid nanoparticles comprise at least: (i) a cationic lipid and / or a polymer-conjugated lipid as defined herein; and (ii) an mRNA compound comprising an mRNA sequence encoding an antigenic peptide or protein. In other particular embodiments, the lipid nanoparticle composition comprises: (a) a cationic lipid according to formula (I) as described herein, (b) a spheroid; (c) a neutral lipid; (d) a polymer-conjugated lipid, wherein said polymer-conjugated lipid is a compound according to formula (II) as described herein; and (e) an mRNA compound encoding a peptide or a protein. With respect to the cationic lipid, the spheroid, the neutral lipid, the polymer-conjugated lipid, and the mRNA compound encoding a peptide or protein, the same options, preferences, and alternatives described above apply to these characteristics. For example, in one preferred embodiment, the peptide or protein expressed by the mRNA compound is an antigen. The amount of cationic lipid relative to that of the mRNA compound in the lipid nanoparticle can also be expressed as a weight ratio (abbreviated as “m / m”). For example, lipid nanoparticles comprise the mRNA compound in an amount such that a weight ratio of lipid to mRNA in the range of about 20 to about 60, or about 10 to about 50, is achieved. In other embodiments, the mass ratio is in the range of about 30 and about 50. In other embodiments, the ratio of cationic lipid to nucleic acid or mRNA is from about 3 to about 15, such as from about 5 to about 13, from about 4 to about 8, or from about 7 to about 11.In a highly preferred embodiment of the present invention, the total mass ratio of lipids to mRNA is about 40 or 40, i.e., about 40 or 40 times the excess mass to ensure encapsulation of the mRNA. Another preferred RNA / lipid ratio is between about 1 and about 10, about 2 and about 5, about 2 and about 4, or preferably about 3. In addition, the amount of the cationic lipid can be selected taking into account the amount of nucleic acid cargo such as the mRNA compound. In one embodiment, the N / P ratio can ML / a / ZUZZ / UU l oou be in the range of about 1 to about 50. In another embodiment, the range is from about 1 to about 20, from about 1 to about 10, from about 1 to about 5. In a preferred embodiment, these amounts are selected so as to result in an N / P ratio of the lipid nanoparticles or composition in the range of about 10 to about 20. In another highly preferred embodiment, the N / P ratio is 14 (i.e., a 14-fold excess of positive charge to ensure encapsulation of the mRNA). In another highly preferred embodiment, the N / P is 17.5 (i.e., a 17.5-fold excess of positive charge to ensure encapsulation of the mRNA). In this context, the N / P ratio is defined as the molar ratio of the nitrogen atoms (“N”) of the basic nitrogen groups of the cationic lipid to the phosphate groups (“P”) of the nucleic acid that is incorporated into, or associated with, the lipid nanoparticle as a biologically active cargo. The N / P ratio can be calculated on the basis that, for example, 1 pg of RNA typically contains about 3 nmol of phosphate residues, provided that the RNA exhibits a statistical distribution of bases. The “N” value of the decationic lipid or lipidoid can be calculated based on its molecular weight and the relative content of cationic groups. If more than one cationic lipid is present, the N value should be calculated based on all cationic lipids included in the lipid nanoparticles. The total amount of mRNA in the lipid nanoparticles varies and can be defined depending on the w / w ratio of mRNA to total lipid. In one embodiment of the invention, the ratio of mRNA to total lipid is less than 0.06 w / w, preferably between 0.03 and 0.04 w / w. Preferably, the mRNA compound or the coding sequence thereof has a length of about 50 to about 20,000, or 100 to about 20,000 nucleotides, preferably about 250 to about 20,000 nucleotides, more preferably about 500 to about 10,000, even more preferably about 500 to about 5,000. As mentioned, the peptide or protein expressed by the mRNA compound may be an antigen. In other words, the composition comprises an mRNA compound comprising an mRNA sequence encoding an antigenic peptide or protein, or a fragment, variant, or derivative thereof. Such antigens, or antigenic peptides or proteins, may be derived from pathogenic antigens, tumor antigens, allergenic antigens, or autoimmune autoantigens, or fragments or variants thereof, preferably as defined herein. Pathogenic Antigens Pathogenic antigens are derived from pathogenic organisms, in particular bacterial, viral, or protozoological (multicellular) pathogens, which elicit an immunological reaction in the subject, in particular a mammalian subject, more particularly a human. More specifically, pathogenic antigens are preferably surface antigens, e.g., proteins (or protein fragments, e.g., the outer portion of a surface antigen) located on the surface of the virus or the bacterial or protozoological organism. i oou 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 protozoan antigen. The encoded (poly)peptide or protein may consist of or comprise a pathogenic antigen or a fragment, variant, or derivative thereof. Pathogenic antigens are peptide or protein antigens preferably derived from a pathogen associated with an infectious disease that are preferably selected from the group of antigens derived from the pathogens described on pages 21-35 of WO 2018 / 078053 A1, but not limited to; WO 2018 / 078053 is incorporated herein by reference in its entirety. Furthermore, pathogenic antigens are peptide or protein antigens preferably derived from a pathogen associated with an infectious disease that are preferably selected from the group of antigens derived from the pathogens described on page 57, paragraph 3 - page 63, paragraph 2, but not limited to, in WO 2019 / 077001 A1; WO 2019 / 077001 is incorporated herein by reference in its entirety. Still other pathogenic antigens are peptide or protein antigens preferably derived from a pathogen associated with an infectious disease which are preferably selected from antigens derived from the pathogens selected from the group of antigens derived from the pathogens described on page 32, line 26, but not limited to them. - page 34 line 27 in WO 2013120628 A1.Furthermore, in this regard, the pathogen antigen (antigen derived from a pathogen associated with an infectious disease) may preferably be selected from the antigens preferably selected from the group of antigens described on page 34, line 29, but not limited to, page 59, line 5 (in parentheses are the particular pathogen or family of pathogens from which the antigen(s) are derived and the infectious disease with which the pathogen is associated) in WO 2013120628 A1; WO 2013120628 which is incorporated herein by reference in its entirety. Among the preferred antigens expressed by the mRNA compound incorporated into the composition of the invention are pathogens selected, among others, from the group consisting of a SARS coronavirus 2 (SARS-CoV-2), coronavirus nCoV-2019, SARS coronavirus (SARS-CoV), Bunyavirales virus, cytomegalovirus (CMV), dengue virus (DEN-1, DEN-2, DEN-3 and DEN-4), Ebola virus, flavivirus, hepatitis B virus (HBV), herpes simplex virus (HSV), human immunodeficiency virus (HIV), human metapneumovirus (hMPV), human papillomavirus (HPV), human parainfluenza virus (HPIV), influenza virus, E.coli, Lassa mammarenavirus (LASV), MERS coronavirus, Mycobacterium tuberculosis, Nipah virus, Norovirus, Rabies virus, Respiratory syncytial virus (RSV), Rhinovirus, Rota virus, Vaccinia virus, Yellow fever virus, Zika virus, Chlamydia trachomatis (i.e., the chlamydia bacteria that cause chlamydia), and malaria parasites (e.g., Plasmodium falciparum, Plasmodium vivax, Plasmodium malariae, or Plasmodium ovale). In another preferred embodiment, the pathogenic antigen is derived from a SARS coronavirus 2 (SARS-CoV-2), coronavirus nCoV-2019, SARS coronavirus (SARS-CoV), a malaria parasite, an influenza virus, or a rabies virus. Furthermore, the pathogen antigens may be preferentially selected from antigens derived from the selected pathogens, inter alia, from the group consisting of Acinetobacter baumannii, IVIA / a / ZUZZ / UU / oou genus Anaplasma, Anaplasma phagocytofi lum, Ancylostoma brasilense, Ancylostoma duodenale, Arcanobacterium haemolyticum, Ascaris lumbricoides, genus Aspergillus, Astroviridae, genus Babesia, Bacillus anthracis, Bacillus cereus, Bartonella henselae, BK virus, Blastocystis hominis, Blastomyces dermatitidis, Bordetella pertussis, Borrelia burgdorferi, genus Borrelia, Borrelia spp, genus Brucella, Brugia malayi, family Bunyaviridae, Burkholderia cepacia and other Burkholderia species, Burkholderia mallei, Burkholderia pseudomallei, family Caliciviridae, genus Campylobacter, Candida albicans, Candida spp, Chlamydia trachomatis, Chlamydophila pneumoniae, Chlamydophila psittaci, CJD prion, Clonorchis sinensis, Clostridium botulinum, Clostridium difficile, Clostridium perfringens, Clostridium perfringens, Clostridium spp, Clostridium tetani, Clostridium spp coronavirus, Corynebacterium diphtheriae, Coxiella burnetii, virus of the hemorrhagic fever of the Crimea-Congo,Cryptococcus neoformans, genus Cryptosporidium, cytomegalovirus (CMV), Dientamoeba fragilis, Ebolavirus (EBOV, por ejemplo, la glycoproteína de la envoltura), genus Echinococcus, Ehrlichia chaffeensis, Ehrlichia ewingii, genus Ehrlichia, Entamoeba histolytica, genus Enterococcus, genus Enterovirus, Enterovirus, mainly Coxsackie virus A and Enterovirus 71 (EV71), Epidermophyton spp, Epstein-Barr virus (EBV), Escherichia coli 01 57:H7, 01 1 1 y O1 04:H4, Fasciola hepática y Fasciola gigantica, FFI prion, feline immunodeficiency virus (FIV), Filarioidea superfamilia ly, Flavivirus, Francisella tularensis, genus Fusobacterium, Geotrichum candidum, Giardia intestinalis, Gnathostoma spp, GSS prion, Guanarito virus, Haemophilus ducreyi, Haemophilus influenza, Helicobacter pylori, Henipavirus ( virus Henclra Nipah virus), Hepatitis A virus, Hepatitis B virus (VHB), Hepatitis C virus (VHC), Hepatitis D virus, Hepatitis E virus,Histoplasma capsulatum, Hortaea werneckii, Human bocavirus (HBoV), Human metapneumovirus (hMPV), Human parainfluenza virus (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, Mycoplasmapneumoniae, Naegleria fowleri, Necator americanus, Neisseria gonorrhoeae, Neisseria meningitidis, Nocardia asteroides, Nocardia spp, Onchocercavulus, Orientia tsutsugamushi, family Orthomyxoviridae (Influenza), Paracoccidioides brasiliensis, Paragonimus spp, Paragonimus westermani, parvovirus B19, genus Pasteurella,genus Plasmodium, Pneumocystis jirovecii, poliovirus, rhinovirus, rhinovirus, Rickettsia akari, genus Rickettsia, Rickettsia prowazekii, Rickettsia rickettsii, Rickettsia typhi, Rift Valley fever virus, rotavirus (preferably antigen fe . VP8), rubella virus, Sabia virus, genus Salmonella, Sarcoptes scabiei, SARS coronavirus, Schistosoma genus, Shigella genus, Unnamed virus, Hantavirus, Sporothrix schenckii, Staphylococcus genus, Staphylococcus genus, Streptococcus agalactiae, Streptococcus pneumoniae, Streptococcus pyogenes, Strongyloides stercoralis, genus Taenia, Taenia solium, Tick-borne encephalitis virus (TBEV), Toxocara canis or Toxocara cati, Toxoplasma gondii, Treponema pallidum, Trichinella spiralis, Trichomonas vaginalis, Trichophyton spp, Trichuris trichiura, Trypanosoma brucei, Trypanosoma cruzi, Ureaplasma urealyticum, vaccinia virus (preferably fe . immune evasion proteins E3, K3 or B18),varicella zoster virus (VZV), varicella zoster virus (VZV), varicella major or varicella minor, vCJD prion, Venezuelan equine encephalitis virus, Vibrio cholerae, West Nile virus, Western equine encephalitis virus, Wuchereria bancrofti, Yersinia enterocolitica, Yersinia pestis and Yersinia pseudotuberculosis, Zika virus, ZikaSPH2015-Brazil, Z1106033-Suriname, MR766-Uganda or Natal RGN, or an exogenous form, homology, fragment, variant or derivative of any of these proteins. A particular preferred pathogenic antigen is an antigen derived from the pathogenic SARS coronavirus, particularly the spike (S) protein of the SARS coronavirus. In a further embodiment, pathogen antigens useful for treating infections may be selected from the following antigens (the related infection and the related pathogen are indicated in parentheses after the respective antigens; naturally, other antigens which may be derived from the following pathogens may also be selected in parentheses), be derived and used in accordance with the invention): • spike protein (S), a coat protein (E), a membrane protein (M), or a nucleocapsid protein (N), or an immunogenic fragment or variant of any of these (the infectious disease is “COVID-19 disease”; pathogen: SARS coronavirus 2 (SARSCoV-2), nCoV-2019 coronavirus, SARS coronavirus (SARS-CoV)); • spike protein (S), an S1 spike fragment (S1), an envelope protein (E), a membrane protein (M), or a nucleocapsid protein (N) (the infectious disease is MERS infection; pathogen: Middle East respiratory syndrome coronavirus (MERS) coronavirus / MERS-CoV)); • E1 replication protein, E2 regulatory protein, E3 protein, E4 protein, E5 protein, E6 protein, E7 protein, E8 protein, major capsid protein L1, minor capsid protein L2 (the infectious disease is human papillomavirus (HPV) infection; pathogen: human papillomavirus (HPV) or HPV16); • F fusion protein, hemagglutinin-neuramidase HN, glycoprotein G, matrix protein M, phosphoprotein P, nucleoprotein N, polymerase L, hemagglutinin-neuramidase, fusion (F) glycoprotein F0, F1 or F2, recombinant PIV3 / PIV1 fusion glycoprotein (F) and hemagglutinin (HN), protein C, phosphoprotein, protein D, matrix protein (M), nucleocapsid protein (N), viral replicase (L), non-structural protein V (the infectious disease is infection with human parainfluenza virus; pathogen: human parainfluenza virus (HPIV / PIV) serotype hPIV-1, hPIV-2, hPIV-3 or hPIV-4, preferably serotype hPIV-3, preferably PIV3); • fusion glycoprotein (F), glycoprotein G, phosphoprotein P, nucleoprotein N, nucleocapsin protein (infectious disease: hMPV infection; pathogen: human metapneumovirus (hMPV)); • hemagglutinin (HA), neuraminidase (NA), nucleoprotein (NP), M1 protein, M2 protein, NS1 protein, NS2 protein (NEP protein: nuclear export protein), PA protein, PB1 protein (polymerase basic protein 1), PB1-F2 protein and PB2 protein, H10N8, H7N9, H10, H1N1, H3N2 (X31), H1, H2, H3, H4, H5, H6, H7, H8, H9, H10, H11, H12, H13, H14, H15, H16, H17, H18, antigenic subdomains of HA: HA1, HA2, neuraminidase (NA), nucleoprotein (NP), matrix protein 1 (M1), matrix protein 2 (M2), nonstructural protein 1 (NS1), nonstructural protein 2 (NS2), antigen HA7, H7 or H10 and B, pathogen: Orthomyxoviridae family, influenza (flu) virus); • nucleoprotein N, large structural protein L, phosphoprotein P, matrix protein M, glycoprotein G, protein G (the infectious disease is rabies; the pathogen: rabies virus); • HIV p24 antigen, HIV envelope proteins (Gp120, Gp41, Gp160), GAG polyprotein, negative factor protein Nef, transcription transactivator Tat, Brecl (infectious disease HIV; pathogen: human immunodeficiency virus); • major outer membrane protein MOMP, probable outer membrane protein PMPC, outer membrane complex protein B OmcB, heat shock proteins Hsp60 HSP10, IncA protein, type III secretion system proteins, small chain ribonucleotide reductase protein NrdB, plasmid protein Pgp3, chlamydial outer protein N CopN, CT521 antigen, CT425 antigen, CT043 antigen, TC0052 antigen, TC0189 antigen, TC0582 antigen, TC0660 antigen, TC0726 antigen, TC0816 antigen, TC0828 antigen (infectious disease: Chlamydiatrachomatis infection; pathogen: Chlamydiatrachomatis); • pp65 antigen, membrane protein pp15, proximal capsid tegument protein pp150, M45 protein, DNA polymerase UL54, helicase UL105, glycoprotein gM, glycoprotein gN, glycoprotein H, glycoprotein B gB, UL83 protein, UL94 protein, UL99 protein, HCMV selected glycoproteins gH gL, gB, gO, gN and gM, HCMV selected proteins UL83, UL123, UL128, UL130 and UL131A, tegument protein pp150 (pp150), tegument protein pp65 / lower matrix phosphoprotein (pp65), envelope glycoprotein M (UL100), regulatory protein IE1 (UL123), envelope protein (UL128), envelope glycoprotein (130), envelope protein (UL131A), envelope glycoprotein B (UL55), structural glycoprotein N gpUL73 (UL73), structural glycoprotein OgpUL74 (UL74) (infectious disease is cytomegalovirus infection, pathogen: cytomegalovirus (CMV / HCMV)); • capsid protein C, premembrane protein prM, membrane protein M, envelope protein E (domain I, domain II, domain II), NS1 protein, NS2A protein, NS2B protein, NS3 protein, NS4A protein, 2K protein, NS4B protein, NS5 protein (infectious disease Dengue fever, pathogen: dengue viruses (DEN-1, DEN-2, DEN-3 and DEN-4)); • EBOV glycoprotein (GP), EBOV surface GP, wild-type EBOV pro-GP, mature EBOV GP, secreted wild-type EBOV pro-GP, secreted mature EBOV GP, EBOV nucleoprotein (NP), RNA polymerase L and EBOV matrix protein selected from VP35, VP40, VP24 and VP30 (infectious disease: Ebola; pathogen: Ebola virus); • hepatitis B surface antigen HBsAg, hepatitis B core antigen HbcAg, polymerase, Hbx protein, preS2 medium surface protein, L surface protein, large S protein, VP1 viral protein, VP2 viral protein, VP3 viral protein, VP4 viral protein (infectious disease is hepatitis B, pathogen: hepatitis B virus (HBV)); • F fusion protein, F protein, N nucleoprotein, M matrix protein, M2-1 matrix protein, M2-2 matrix protein, P phosphoprotein, SH small hydrophobic protein, major surface glycoprotein G, L polymerase, NS1 nonstructural protein 1, NS2 nonstructural protein 2, RSV attachment protein (G) (G glycoprotein), Fusion (F) glycoprotein (F glycoprotein), N nucleoprotein, P phosphoprotein, L large polymerase protein, M matrix protein (M, M2), SH small hydrophobic protein, NS1 nonstructural protein, NS2 nonstructural protein, RSV membrane-bound F protein, DS-CavI membrane-bound (stabilized prefusion RSV F protein) (infectious disease is infection with viruses (RSV), pathogen: Respiratory syncytial virus (RSV)); • secretory antigen SssA (genus Staphylococcus, staphylococcal food poisoning); secretory antigen SssA (genus Staphylococcus, e.g., aureus, staphylococcal infection); molecular chaperone DnaK, cell surface lipoprotein Mpt83, lipoprotein P23, phosphate transport system permease protein pstA, 14 kDa antigen, fibronectin-binding protein C FbpC1, alanine dehydrogenase TB43, glutamine synthetase 1, ESX-1 protein, CFP10 protein, TB10.4 protein, MPT83 protein, MTB12 protein, MTB8 protein, Rpf-like proteins, MTB32 protein, MTB39 protein, crystal protein, heat shock protein HSP65, PST-S protein (the infectious disease is Tuberculosis; pathogen: Mycobacterium tuberculosis); • genome polyprotein, E protein, M protein, capsid protein C, NS3 protease, NS1 protein, NS2A protein, AS2B protein, NS4A protein, NS4B protein, NS5 protein (the infectious disease is yellow fever; the pathogen: yellow fever virus); • circumsporozoite protein (CSP) (infectious disease is malaria; pathogen: P. falciparum and P. vivax);and • Zika virus proteins according to WO 2017 / 140905 A1, i.e. Zika virus capsid protein (C), Zika virus premembrane protein (prM), Zika virus pr protein (pr), Zika virus membrane protein (M), Zika virus envelope protein (E), Zika virus nonstructural protein, ZIKV prME antigen, ZIKV capsid protein, premembrane / membrane protein, ZIKV envelope protein, ZIKV nonstructural protein 1, ZIKV nonstructural protein 2A, ZIKV nonstructural protein 2B, ZIKV nonstructural protein 3, ZIKV nonstructural protein 4A, ZIKV nonstructural protein 4B, ZIKV nonstructural protein 5 or a Zika virus envelope protein (E) wherein the fusion loop of domain II is mutated according to WO 2017 / 140905 A1;WO 2017 / 140905 which is incorporated herein by reference in its entirety (the infectious disease is Zika virus infection; the pathogen: Zika virus); In some embodiments of the present invention, methods for inducing an antigen-specific immune response in a subject are provided, comprising administering to the subject any of the RNA (e.g., mRNA) vaccines provided herein in an amount effective to produce an antigen-specific immune response vaccine. In some embodiments, the RNA vaccine (e.g., mRNA) is a coronavirus 2 SARS (SARS-CoV-2), coronavirus nCoV-2019, SARS coronavirus (SARS-CoV), Bunyaviruses, cytomegalovirus (CMV), dengue virus (DEN-1, DEN-2, DEN-3 and DEN-4), Ebola virus, Flavivirus, hepatitis B virus (HBV), herpes simplex virus (HSV), human immunodeficiency virus (HIV), human metapneumovirus (hMPV), human papiloma virus (HPV), human parainfluenza virus (HPV), influenza virus, extraintestinal pathogenic E. coli, Lassa mammarenavirus (LASV), MERS coronavirus, Mycobacterium tuberculosis, Nipah virus, norovirus, rabies virus, respiratory syncytial virus (RSV), rhinovirus, vaccinia virus, flu virus amarilla, Zika virus, Chlamydia trachomatis (e.g., the chlamydia bacteria causes chlamydia) and malaria parasites (e.g., Plasmodium falciparum, Plasmodium vivax, Plasmodium malariae or Plasmodium ovale).In another preferred embodiment, the pathogen antigen is derived from a SARS-CoV-2 coronavirus, a SARS-CoV-2 coronavirus, a malaria parasite, an influenza virus, or a rabies virus. In other embodiments, the RNA (e.g., mRNA) vaccine is a COVID-19, rabies, influenza, or malaria vaccine. In some embodiments, the RNA (e.g., mRNA) vaccine is a combination vaccine comprising a combination of influenza vaccines (a broad-spectrum influenza vaccine). In some embodiments, an antigen-specific immune response comprises a T cell response or a B cell response. In some embodiments, a method for producing an antigen-specific immune response comprises administering to a subject a single dose (i.e., without a booster dose) of a SARS coronavirus 2 (SARS-CoV-2), coronavirus nCoV-2019, SARS coronavirus (SARS-CoV), Bunyavirales virus, cytomegalovirus (CMV), dengue virus (DEN-1, DEN-2, DEN-3, and DEN-4), Ebola virus, flavivirus, hepatitis B virus (HBV), herpes simplex virus (HSV), Human Immunodeficiency Virus (HIV), Human Metapneumovirus (hMPV), Human Papillomavirus (HPV), Human Parainfluenza Virus (HPIV), Influenza virus, E.coli, Lassa mammarenavirus (LASV), MERS coronavirus, Mycobacterium tuberculosis, Nipah virus, norovirus, rabies virus, respiratory syncytial virus (RSV), rhinovirus, rotavirus, vaccinia virus, yellow fever virus, Zika virus, Chlamydia trachomatis (i.e., the bacteria that causes chlamydia), and malaria parasites (e.g., Plasmodium falciparum, Plasmodium vivax, Plasmodium malariae, or Plasmodium ovale). In another preferred embodiment, the pathogenic antigen is derived from a SARS coronavirus 2 (SARS-CoV-2), coronavirus nCoV-2019, SARS coronavirus (SARS-CoV), a malaria parasite, an influenza virus, or a rabies virus, (e.g., mRNA) vaccine of the present disclosure. In some embodiments, a method further comprises administering to the subject a second (booster) dose of a SARS coronavirus 2 (SARS-CoV-2), coronavirus nCoV-2019, SARS coronavirus (SARS-CoV), Bunyavirales virus, cytomegalovirus (CMV), dengue virus (DEN-1, DEN-2, DEN-3, and DEN-4), Ebola virus, flavivirus, hepatitis B virus (HBV), herpes simplex virus (HSV), human immunodeficiency virus (HIV), human metapneumovirus (hMPV), human papillomavirus (HPV), human parainfluenza virus (HPIV), influenza virus, extraintestinal pathogenic E. coli, Lassa mammarenavirus (LASV), MERS coronavirus, Mycobacterium tuberculosis, Nipah virus, norovirus, rabies virus, respiratory syncytial virus (RSV), Rhinovirus, Rota virus, Vaccinia virus, Yellow Fever Virus, Zika virus, 100 Chlamydia trachomatis (i.e., the chlamydia bacterium that causes chlamydia) and malaria parasites (e.g., Plasmodium falciparum, Plasmodium vivax, Plasmodium malariae, or Plasmodium ovale). In another preferred embodiment, the pathogen antigen is derived from a SARS coronavirus 2 (SARS-CoV-2), coronavirus nCoV-2019, SARS coronavirus (SARS-CoV), a malaria parasite, an influenza virus, or a rabies virus. An RNA (e.g., mRNA) vaccine may be administered. In some embodiments, subjects exhibit a seroconversion rate of at least 80% (e.g., at least 85%, at least 90%, or at least 95%) after the first or second (booster) dose of the vaccine. Seroconversion is the period of time during which a specific antibody develops and becomes detectable in the blood. Once seroconversion has occurred, a virus can be detected in blood tests for the antibody. During an infection or immunization, antigens enter the blood, and the immune system begins to produce antibodies in response. Before seroconversion, the antigen itself may or may not be detectable, but antibodies are considered absent. During seroconversion, antibodies are present but not yet detectable. At any time after seroconversion, antibodies can be detected in the blood, indicating a past or current infection.In some embodiments, an RNA (e.g., mRNA) vaccine is administered to a subject by intradermal injection, intramuscular injection, or intranasal administration. In some embodiments, an RNA (e.g., mRNA) vaccine is administered to a subject by intramuscular injection. Some embodiments of the present disclosure provide methods for inducing an antigen-specific immune response in a subject, including administering to a subject a SARS coronavirus 2 (SARS-CoV-2), coronavirus nCoV-2019, SARS coronavirus (SARS-CoV), Bunyavirales virus, cytomegalovirus (CMV), dengue virus (DEN-1, DEN-2, DEN-3, and DEN-4), Ebola virus, flavivirus, hepatitis B virus (HBV), herpes simplex virus (HSV), human immunodeficiency virus (HIV), human metapneumovirus (hMPV), human papillomavirus (HPV), human parainfluenza virus (HPIV), influenza virus, E.coli extraintestinal pathogen, Lassa mammarenavirus (LASV), MERS coronavirus, Mycobacterium tuberculosis, Nipah virus, norovirus, Rabies virus, Respiratory syncytial virus (RSV), rhinovirus, rotavirus, vaccinia virus, yellow fever virus, Zika virus, Chlamydia trachomatis (i.e., the bacteria that causes chlamydia), and malaria parasites (e.g., Plasmodium falciparum, Plasmodium vivax, Plasmodium malariae, or Plasmodium ovale). In another preferred embodiment, the pathogenic antigen is derived from a SARS coronavirus 2 (SARS-CoV-2), coronavirus nCoV-2019, SARS coronavirus (SARS-CoV), a malaria parasite, an influenza virus, or a rabies virus. RNA vaccine (e.g., mRNA) in an amount effective to produce an antigen-specific immune response in a subject. Antigen-specific immune responses in a subject can be determined, in some embodiments, by assaying antibody titer (for the titer of an antibody that binds to a SARS coronavirus 2 (SARS-CoV-2), coronavirus nCoV-2019, SARS coronavirus (SARS-CoV), Bunyavirales virus, cytomegalovirus (CMV), dengue virus (DEN-1, DEN-2, DEN-3, and DEN-4), Ebola virus, flavivirus, hepatitis B virus (HBV), herpes simplex virus (HSV).), human immunodeficiency virus l oou 101 (HIV), human metapneumovirus (hMPV), human papillomavirus (HPV), human parainfluenza virus (HPIV), influenza virus, extraintestinal pathogenic E. coli, Lassa mammarenavirus (LASV), MERS coronavirus, Mycobacterium tuberculosis, Nipah virus, Norovirus, Rabies virus, Respiratory syncytial virus (RSV), Rhinovirus, Rota virus, Vaccinia virus, Yellow fever virus, Zika virus, Chlamydia trachomatis (i.e., the bacterium that causes chlamydia), or malaria parasite (e.g.,, Plasmodium falciparum, Plasmodium vivax, Plasmodium malariae or Plasmodium ovale) antigen polypeptide) after administration to the subject of any of the SARS coronavirus 2 (SARS-CoV-2), coronavirus nCoV-2019, SARS coronavirus (SARS-CoV), Bunyavirales viruses, cytomegalovirus (CMV), dengue viruses (DEN-1, DEN-2, DEN-3 and DEN-4), Ebola virus, Flaviviridae, hepatitis B virus (HBV), herpes simplex virus (HSV), human immunodeficiency virus (HIV), human metapneumovirus (hMPV), human papillomavirus (HPV), human parainfluenza virus (HPIV), influenza virus, E.coli, Lassa mammarenavirus (LASV), MERS coronavirus, Mycobacterium tuberculosis, Nipah virus, norovirus, rabies virus, respiratory syncytial virus (RSV), rhinovirus, rotavirus, Vaccinia virus, yellow fever virus, Zika virus, Chlamydia trachomatis (i.e., chlamydia bacteria that causes chlamydia), or malaria parasite (e.g., Plasmodium falciparum, Plasmodium vivax, Plasmodium malariae, or Plasmodium ovale) RNA (e.g., mRNA) vaccines of the present disclosure. In some embodiments, the anti-antigenic polypeptide antibody titer produced in the subject is increased by at least 1 log relative to a control. In some embodiments, the anti-antigenic polypeptide antibody titer produced in the subject is increased by 1-3 log relative to a control. Tumor Antigens In a further preferred embodiment, the mRNA compound comprising an mRNA encodes a tumor antigen, preferably as defined herein, or a fragment or variant thereof, wherein the tumor antigen is preferably selected from the group consisting of tumor antigens described, but not limited to, on pages 47-51 of WO 2018 / 078053 A1; WO 2018 / 078053 A1 is incorporated herein by reference in its entirety. Furthermore, cytokines, chemokines, suicide enzymes and gene products, inducers of apoptosis, endogenous angiogenesis inhibitors, heat shock proteins, tumor antigens, innate immune activators, antibodies directed against proteins associated with tumor or cancer development, useful for the present invention are useful for the treatment of cancer., are selected from the group of cytokines, chemokines, suicide enzymes and gene products, inducers of apoptosis, inhibitors of endogenous angiogenesis, heat shock proteins, tumor antigens, innate immune activators, antibodies directed against proteins associated with tumors or cancer, among others, development as described in Table 1, Table 2, Table 3, Table 4, Table 5, Table 6, Table 7, Table 8, Table 9, Table 10, Table 11 and Table 12 of WO 2016 / 170176; WO 2016 / 170176 and especially Tables 1-12 are specifically incorporated herein by reference in their entirety. Therapeutic proteins / use for the treatment or prophylaxis of any hereditary or acquired disease. 102 In a further embodiment, the active ingredient is a nucleic acid compound comprising at least one coding sequence, where at least one coding sequence encodes a peptide or protein, where the protein is a therapeutic protein, or a fragment or variant of a therapeutic protein. In this context, a therapeutic peptide, protein or fragment thereof may be any peptide compound useful for the prevention, management, amelioration, treatment or therapy of a disease or condition in a subject, such as an animal, and in particular in a human subject. Thus, in one embodiment, the mRNA comprising at least one coding sequence may encode (a) a peptide or protein, or a fragment or variant thereof, wherein the peptide or protein is an antigen, wherein the antigen is preferably derived from pathogenic antigens, tumor antigens, allergenic antigens, or autoimmune autoantigens, or a fragment or variant thereof; or (b) a therapeutic protein or a fragment or variant thereof. The therapeutic protein may, for example, be selected from the group consisting of (i) therapeutic proteins for use in enzyme replacement therapy for the treatment of metabolic, endocrine, or amino acid disorders or for use in replacing a missing, deficient, or mutated protein; (i) Therapeutic proteins for use in the treatment of blood disorders, diseases of the circulatory system, diseases of the respiratory system, infectious diseases or immunodeficiencies; (II) therapeutic proteins for use in the treatment of cancer or tumor diseases; (iv) therapeutic proteins for use in hormone replacement therapy; (v) therapeutic proteins for use in the reprogramming of somatic cells into pluripotent or omnipotent stem cells; (vi) therapeutic proteins for use as adjuvants or immunostimulants; (vii) therapeutic proteins that are a therapeutic antibody; (viii) therapeutic proteins that are a gene editing agent; and (ix) therapeutic proteins for use in the treatment or prevention of a liver disease selected from the group consisting of liver fibrosis, liver cirrhosis, and liver cancer. In a specific embodiment, the therapeutic protein, or a fragment or variant thereof, is selected from: Therapeutic proteins for use in enzyme replacement therapy for the treatment of metabolic, endocrine or amino acid disorders or for use in replacing a missing, deficient or mutated protein, including acid sphingomyelinase, Adipotide, Agalsidase-beta, Alglucosidase, alpha-galactosidase A, alpha-glucosidase, alpha-L-iduronidase, alpha-N-acetylglucosaminidase, amphiregulin, angiopoietins (Ang1, Ang2, Ang3, Ang4, ANGPT1_2, ANGPTL3, ANGPTL4, ANGPTL5, ANGPTL6, ANGPTL7), ATPase, Cu(2+) transporter polypeptide beta (ATP7B), argininosuccinate synthetase (ASS1), 103 betacellulin, beta-glucuronidase, bone morphogeneic proteins BMP (BMP1, BMP2, BMP3, BMP4, BMP5, BMP6, BMP7, BMP8a, BMP8b, BMP10, BMP15), CLN6 protein, epidermal growth factor (EGF), Epigen, epiregulin, fibroblast growth factor (FGF, FGF-1, FGF-2, FGF-3, FGF-4, FGF-5, FGF6, 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), fumaryl aceto acetate hydrolase (AHF), galsulfase, ghrelin, glucocerebrosidase, GM-CSF, heparin-binding EGF-like growth factor (B-EGF), hepatocyte growth factor HGF, hepcidin, human albumin, increased albumin leakage, idursulfase (iduronate-2-sulfatase), integrins ανβ3, ανβ5 and α5β1, iuduronate sulfatase, laronidase, N-acetylgalactosamine-4-sulfatase (rhASB; galsulfase, arylsulfatase A (ARSA), arylsulfatase B (ARSB)), N-acetylglucosamine-6-sulfatase, nerve growth factor (NGF,brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and neurotrophin 4 / 5 (NT-4 / 5), Neuregulin (NRG1, NRG2, NRG3, NRG4), neuropilin (NRP-1, NRP-2), obestatin, phenylalanine hydroxylase (PAH), phenylalanine ammonia lyase (PAL), platelet-derived growth factor (PDGF (PDGF-A, PDGF-B, PDGF-C, PDGF-D), TGF beta receptors (endoglin, TGF-beta 1 receptor, TGF-beta 2 receptor, TGF-beta 3 receptor), thrombopoietin (THPO) (megakaryocyte growth and development factor (MGDF)), transforming growth factor (TGF (TGF-a, TGF-beta (TGFbetal, TGFbeta2 and TGFbeta3))), VEGF (VEGF-A, VEGF-B, VEGF-C, VEGF-D, VEGF-E, VEGF-F and PIGF), nesiritide, trypsin, adrenocorticotrophic hormone (ACTH), atrial natriuretic peptide (ANP), cholecystokinin, gastrin, leptin, oxytocin, somatostatin, vasopressin (antidiuretic hormone), calcitonin, exenatide, growth hormone (GH), somatotropin, Insulin,insulin-like growth factor 1 IGF-1, mecasermin rinfabate, IGF-1 analogue, Mecasermin, IGF-1 analogue, pegvisomant, pramlintide, teriparatide (human parathyroid hormone residues 1-34), becaplermin, dibotermin-alf a (bone morphogenesis protein 2), histrelin acetate (gonadotropin-releasing hormone; GnRH), octreotide, hepatocyte nuclear factor 4 alpha (HNF4A), CCAAT / enhancer-binding protein alpha (CEBPA), fibroblast growth factor 21 (FGF21), extracellular matrix protease or human collagenase MMP1, hepatocyte growth factor (HGF), TNF-related apoptosis-inducing ligand (TRAIL), opioid growth factor-like receptor 1 (OGFRL1), clostridial collagenase type II, relaxin 1 (RLN1), relaxin 2 (RLN2), relaxin 3 (RLN3) and palifermin (keratinocyte growth factor; KGF);, Therapeutic proteins for use in the treatment of blood disorders, circulatory system diseases, respiratory system diseases, cancer or tumor diseases, infectious diseases or immunodeficiencies, including Alteplase (tissue plasminogen activator;tPA), Anistreplase, Antithrombin III (AT-III), Bivalirudin, Darbepoetin-alpha, Drotrecogin-alpha (activated protein C, erythropoietin, epoetin-alpha, erythropoietin, erthropoietin, Factor IX, Factor Vllla, Factor VIII, Lepirudin, Protein C concentrate, Reteplase (tPA deletion mutein), Streptokinase, Tenecteplase, Urokinase, Angiostatin, Anti-CD22 immunotoxin, Denileukin diftitox, Immunocyanin, MPS (metallopanestimulin), Aflibercept, Endostatin, Collagenase, Human deoxyribonuclease I, Dornase, Hyaluronidase, Papain, Lasparaginase, Peg-asparaginase, Rasburicase, Human chorionic gonadotropin (HCG), Follicle-stimulating hormone human (FSH), lutropin alpha, prolactin, alpha-1-proteinase inhibitor, lactase, enzymes; 104 pancreatic (lipase, amylase, protease), adenosine deaminase (bovine pegademase, PEG-ADA), abatacept, alefacept, anakinra, etanercept, interleukin-1 (IL-1) receptor antagonist, anakinra, thymulin, tumor necrosis factor alpha antagonist, enf uvirtide, and thymosin a1; Therapeutic proteins for use in the treatment of cancer or tumor diseases, including cytokines, chemokines, suicide gene products, immunogenic proteins or peptides, inducers of apoptosis, inhibitors of angiogenesis, heat shock proteins, tumor antigens, beta-catenin inhibitors, STING pathway activators, checkpoint modulators, innate immune activators, antibodies, dominant negative receptors and decoy receptors, myeloid-derived suppressor cell (MDSC) inhibitors, IDO pathway inhibitors, and proteins or peptides that bind to apoptosis inhibitors; therapeutic proteins selected from adjuvant or immunostimulatory proteins, including human adjuvant proteins, particularly pattern recognition receptors TLR1, TLR2, TLR3, TLR4, TLR5, TLR6, TLR7, TLR8, TLR9, TLR10, TLR11; NOD1, NOD2, NOD3, NOD4, NOD5, NALP1, NALP2, NALP3, NALP4, NALP5, NALP6, NALP6, NALP7, NALP7, NALP8, NALP9, NALP10, NALP11, NALP12, NALP13, NALP14, IPAF, NAIP, CUTA, RIG-I, MDA5 and LGP2, the signal transducers of TLR signaling including adaptor proteins including, for example, Trif and Cardif; components of Small-GTPases signaling (RhoA, Ras, Rac1, Cdc42, Rab, etc.), components of PIP signaling (PI3K, Src-Kinases, etc.), components of MyD88-dependent signaling (MyD88, IRAK1, IRAK2, IRAK4, TIRAP, TRAF6, etc.), components of MyD88-independent signaling (TICAM1, TICAM2, TRAF6, TBK1, IRF3, TAK1, IRAK1, etc.);activated kinases including, for example, Akt, MEKK1, MKK1, MKK3, MKK4, MKK6, MKK7, ERK1, ERK2, GSK3, PKC kinases, PKD kinases, GSK3 kinases, JNK, p38MAPK, TAK1, IKK and TAK1; activated transcription factors including, for example, NF-kB, c-Fos, c-Jun, c-Myc, CREB, AP-1, Elk-1, ATF2, IRF-3, IRF-7, heat shock proteins, such as HSP10, HSP60, HSP65, HSP70, HSP75 and HSP90, gp96, fibrinogen, Typlll repeat the extra A domain of fibronectin; or components of the complement system, including C1q, MBL, C1r, C1s, C2b, Bb, D, MASP-1, MASP-2, C4b, C3b, C5a, C3a, C4a, C5b, C6, C7, C8, C9, CR1, CR2, CR3, CR4, C1qR, C1INH, C4bp, MCP, DAF, Η, I, P, and CD59, or induced target genes including, for example, beta-defensin, cell surface proteins;human adjuvant proteins including trif, flt-3 ligand, Gp96 or fibronectin, cytokines that 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-1alpha, RANTES, Eotaxin, CCL21; cytokines that are released from macrophages, including IL-1, IL-6, IL-8, IL-12 and TNF-alpha; as well as IL-1 R1 and IL-1 alpha; Bacterial proteins (adjuvants), including bacterial heat shock proteins or chaperones, including Hsp60, Hsp70, Hsp90, HsplOO; OmpA (outer membrane protein) of Gram-negative bacteria; OspA; bacterial porins, including OmpF; bacterial toxins, including pertussis toxin (PT) of Bordetella pertussis, pertussis adenylate cyclase toxins CyaA and CyaC of Bordetella pertussis, pertussis toxin PT-9K / 129G mutant, pertussis adenylate cyclase toxins CyaA and CyaC of Bordetella pertussis, tetanus toxin, cholera toxin (CT), tetanus toxin B subunit IVIA / a / ZUZZ / UU l oou 105 cholera, cholera toxin CTK63 mutant, CT mutant CTE112K, Escherichia coli heat-labile enterotoxin (LT), heat-labile enterotoxin (LTB) subunit Escherichia coli heat-labile enterotoxin mutants with reduced toxicity, including LTK63, LTR72; phenol-soluble module; Helicobacter pylori neutrophil-activating protein (HP-NAP); surfactant protein D; Borrelia burgdorferi outer surface protein A lipoprotein, Mycobacterium tuberculosis Ag38 (38 kDa antigen); bacterial fimbriae proteins; Vibrio cholerae CT enterotoxin, pilin from pili of gram-negative bacteria and surfactant protein A yf bacterial lagellins; protozoan proteins (adjuvants), including Tc52 from Trypanosoma cruz!, PFTG from Trypanosoma gondii, protozoan heat shock proteins, LelF from Leishmania spp., profiling-like protein from Toxoplasma gondii; Viral proteins (adjuvants), including respiratory syncytial virus fusion glycoprotein (F protein), MMT virus envelope protein, mouse leukemia virus protein, wild-type measles virus hemagglutinin protein; Fungal proteins (adjuvants), including fungal immunomodulatory protein (FIP; LZ-8); proteins of animal origin, including keyhole limpet hemocyanin (KLH); Therapeutic proteins used for hormone replacement therapy, where the hormones include estrogen, progesterone or progestins, and testosterone; and therapeutic proteins used to reprogram somatic cells into pluripotent or omnipotent stem cells, including Oct-3 / 4, Sox gene family (Sox1, Sox2, Sox3, and Sox15), Klf family (Klf 1, Klf2, Klf4, and Klf5), Myc family (c-myc, L-myc, and N-myc), Nanog, and LIN28. This invention includes methods for preventing, ameliorating, or treating a disease or condition in a subject in need thereof, comprising administering to the subject a composition as described herein. The compositions of this invention may be used in the treatment of the human or animal body. In this context, particularly preferred therapeutic proteins that can be used, inter alia, in the treatment of metabolic or endocrine disorders are selected from those described in Table A (in combination with Table C) of WO 2017 / 191274. Furthermore, diseases that can preferably be treated with the composition of the invention, preferably selected from infectious diseases, neoplasms (e.g., cancer or tumor diseases), diseases of the blood and hematopoietic 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, are described in WO 2017 / 191274 on pages 95, line 4 - page 103, line 24.Other particularly preferred therapeutic proteins that can be used, inter alia, in the treatment of metabolic or endocrine disorders are described in Table 1 of WO 2017 / 191274, which also refers to specific target / disease combinations, incorporated herein by reference, and also sequences. WO 2017 / 191274 incl. Tables A / C and Table 1 are incorporated herein by reference in their entirety. 106 In preferred embodiments, artificial nucleic acid (RNA) molecules, (pharmaceutical) compositions, or vaccines or kits are used for the treatment or prophylaxis of infectious diseases. The term "infection" or "infectious disease" refers to the invasion and multiplication of microorganisms such as bacteria, viruses, and parasites that are not normally present in the body. An infection may be asymptomatic and subclinical, or it may cause symptoms and be clinically evident. An infection may remain localized or may spread through the blood or lymphatic system to become systemic. Infectious diseases in this context preferably include viral, bacterial, fungal, or protozoological infectious diseases.In particular, infectious diseases are selected from the group described starting on page 157, section “Infectious diseases” (ending on page 160) of WO 2019 / 077001 A1; WO 2019 / 077001 A1 is incorporated herein by reference in its entirety. In this context, further particularly preferred examples of diseases and / or conditions for which the compositions of the invention or the translatable molecules of the invention can be used for treatment are described in Table 2 of US 2019 / 0002906; US 2019 / 0002906 incl. Table 2 is incorporated herein by reference in its entirety. Liver diseases or liver-related diseases in animals, more particularly in humans, may include, among others, congenital diseases or acquired diseases, for example, viral and parasitic infectious diseases, oncological pathologies such as primary tumors and metastases, metabolic diseases, amino acid and / or endocrine disorders as well as inflammatory, immune and autoimmune conditions.The liver diseases that can preferably be treated with the composition of the invention are selected, among others, from the group consisting of Hepatitis C, Hepatitis B, Hepatitis, Hepatitis A, Cirrhosis, Liver cancer, Hepatocellular carcinoma, Hepatic encephalopathy, Autoimmune hepatitis, Wilson's disease, alpha-1 antitrypsin deficiency (AAT deficiency), hepatitis D, phenylketonuria (PKU), Wilson's disease (hepatolentil degeneration), Tyrosinemia Type I (FAH deficiency), Alagille syndrome, Portal hypertension, steatohepatitis, chronic hepatitis and hepatitis E. In a further preferred embodiment, the compositions of the present invention may be used in a method for treating or preventing a disorder, wherein the disorder is a liver disease, preferably selected from the group consisting of liver fibrosis, liver cirrhosis, and liver cancer. Accordingly, the mRNA comprising at least one coding sequence may encode a therapeutic protein or a fragment or variant thereof for use in the treatment or prevention of a liver disease selected from the group consisting of liver fibrosis, liver cirrhosis, and liver cancer.Furthermore, preferably, the mRNA for treating or preventing liver diseases or a liver disease selected from the group consisting of liver fibrosis, liver cirrhosis, and liver cancer encodes a peptide or protein selected from the group consisting of hepatocyte nuclear factor 4 alpha (HNF4A), CCAAT / enhancer-binding protein alpha (CEBPA), fibroblast growth factor 21 (FGF21), extracellular matrix protease or human collagenase MMP1, hepatocyte growth factor (HGF), TNF-related apoptosis-inducing ligand (TRAIL), opioid-like growth factor receptor 1. 107 (OGFRL1), clostridial collagenase type II, Relaxin 1 (RLN1), Relaxin 2 (RLN2) and Relaxin 3 (RLN3). In this regard, the liver disease-specific disclosure of WO 2018 / 104538 A1, as well as the sequences described in WO 2018 / 104538 A1, are incorporated herein by reference. Other antigens Other antigens useful for the present invention are listed in WO 2018 / 078053 on pages 48-51; WO 2018 / 078053 is incorporated herein by reference in its entirety. Allergenic antigens and autoimmune autoantigens As mentioned, the mRNA compound comprised in the composition of the invention may, according to some embodiments, encode an antigen representing an allergen, or an allergenic antigen or an autoantigen, also called an autoantigen or autoimmune antigen. Such antigens and autoantigens associated with allergies or allergic diseases (allergens or allergenic antigens) are derived from or preferably selected from, but not limited to, the group of antigens described on pages 59-73 of WO 2018 / 078053 A1; WO 2018 / 078053 A1 is incorporated herein by reference in its entirety. Checkpoint modulators / checkpoint inhibitorsIn the context of the present invention, an immune checkpoint protein, a checkpoint modulator, or a checkpoint inhibitor is typically a molecule, such as a protein (e.g., an antibody), a dominant negative receptor, a decoy receptor, or a ligand, or a fragment or variant thereof, that modulates the function of an immune checkpoint protein, e.g., inhibits or reduces the activity of checkpoint inhibitors (or inhibitory checkpoint molecules), or stimulates or potentiates the activity of checkpoint stimulators (or stimulatory checkpoint molecules). Therefore, checkpoint modulators, as defined herein, influence the activity of checkpoint molecules. In this context, inhibitory checkpoint molecules are defined as checkpoint inhibitors and may be used synonymously.In addition, stimulatory checkpoint molecules are defined as checkpoint stimulants and can be used synonymously. In a further preferred embodiment, the mRNA compound comprising an mRNA encodes an immune checkpoint protein, checkpoint modulators or checkpoint inhibitor, preferably as defined herein, or a fragment or variant thereof, wherein the immune checkpoint protein, checkpoint modulators or checkpoint inhibitor is preferably selected from the group consisting of immune checkpoint proteins, checkpoint modulators or checkpoint inhibitors described on pages 51-56 of WO 2018 / 078053 A1, but not limited to them; WO 2018 / 078053 A1 is incorporated herein by reference in its entirety. 108 RNA elements. mRNA elements According to certain embodiments of the present invention, the mRNA sequence is mono-, bi-, or multicistronic, preferably as defined herein. The coding sequences in a bicistronic or multicistronic mRNA preferably encode distinct peptides or proteins as defined herein or a fragment or variant thereof. Preferably, coding sequences encoding two or more peptides or proteins may be separated in the bi- or multicistronic mRNA by at least one IRES (internal ribosomal entry site) sequence, as defined below. Thus, the term “encoding two or more peptides or proteins” may mean, but is not limited to, that the bicistronic or multicistronic mRNA may encode, for example, at least two, three, four, five, six, or more (preferably different) peptides or proteins or fragments or variants thereof within the definitions provided herein.More preferably, but not limited thereto, the bi- or even multicistronic mRNA may encode, for example, at least two, three, four, five, six or more (preferably different) peptides or proteins as defined herein or fragments or variants thereof as defined herein. In this context, a so-called IRES (internal ribosomal entry site) sequence as defined above may function as a single ribosome binding site but may also serve to provide a bi- or even multicistronic mRNA as defined above, encoding several peptides or proteins that are to be translated by the ribosomes independently of one another. Examples of IRES sequences that may be used according to the invention are those of picornaviruses (e.g. FMDV), pestiviruses (CFFV), poliovirus (PV), encephalomyocarditis virus (ECMV), foot and mouth disease virus (FMDV), hepatitis C virus (HCV),. According to a further embodiment, at least one coding region of the mRNA sequence according to the invention may encode at least two, three, four, five, six, seven, eight and more peptides or proteins (or fragments and derivatives thereof) as defined herein linked with or without an amino acid linker sequence, wherein said linker sequence may comprise rigid linkers, flexible linkers, cleavable linkers (e.g., self-cleaving peptides) or a combination thereof. There, the peptides or proteins may be identical or different or a combination thereof. Particular combinations of peptides or proteins may be encoded by said mRNA encoding at least two peptides or proteins as explained herein (also referred to herein as “multi-antigen / mRNA constructs”). In another preferred embodiment, the mRNA compound comprised in the composition encodes a pathogen antigen whose amino acid sequence is unmodified relative to the respective wild-type amino acid sequence. In this case, the mRNA compound may also comprise a coding region with a nucleic acid sequence that is unmodified relative to the respective wild-type mRNA sequence. For example, the mRNA compound may be a naturally occurring, unmodified mRNA. As used herein, naturally occurring, unmodified mRNA encompasses mRNA generated in vitro, without chemical modifications or changes in sequence. 109 Modifications v mRNA sequences In another embodiment of the invention, the mRNA compound comprises an artificial mRNA. In this context, artificial mRNA encompasses mRNA with chemical modifications, sequence modifications, or non-natural sequences. Chemical modificationsAccording to another embodiment of the invention, the mRNA compound comprised in the composition comprises at least one chemical modification. In one embodiment, the chemical modification may be selected from the group consisting of base modifications, sugar modifications, backbone modifications, and lipid modifications. A backbone modification in relation to the present invention is a modification wherein the backbone phosphates of the nucleotides contained in an mRNA compound comprising an mRNA sequence as defined herein are chemically modified. A sugar modification in relation to the present invention is a chemical modification of the sugar of the nucleotides of the mRNA compound comprising an mRNA sequence as defined herein.Furthermore, a base modification in relation to the present invention is a chemical modification of the base moiety of the nucleotides of the mRNA compound comprising an mRNA sequence. In this context, the nucleotide analogs or modifications are preferably selected from nucleotide analogs that are applicable for transcription and / or translation. Sugar modifications Modified nucleosides and nucleotides, which can be incorporated into a modified mRNA compound comprising an mRNA sequence as described herein, can be modified at the sugar moiety. For example, the 2' hydroxyl group (OH) can be modified or replaced with various different “oxy” or “deoxy” substituents. Examples of modifications of the “oxy” 2' hydroxyl group include, but are not limited to, alkoxy or aryloxy (-OR, e.g., R=H, alkyl, cycloalkyl, aryl, aralkyl, heteroaryl, or sugar); polyethylene glycols (PEGs), -O(CH2CH2O)nCH2CH2OR; “locked” nucleic acids (LNAs) in which the 2' hydroxyl is connected, e.g., by a methylene bridge, to the 4' carbon of the same ribose sugar; and amino groups (Ό-amino, where the amino group, e.g., NRR, can be alkylamino, dialkylamino, heterocyclyl, arylamino, diarylamino, heteroarylamino or diheteroarylamino, ethylenediamino, polyamino) or aminoalkoxy. “Deoxy” modifications include hydrogen, amino (e.g., NH2; alkylamino, dialkylamino, heterocyclyl, arylamino, diarylamino, heteroarylamino, diheteroarylamino, or amino acid); or the amino group may be attached to the sugar through a linker, wherein the linker comprises one or more of the C, N, and O atoms. The sugar moiety can also contain one or more carbons that have the opposite stereochemical configuration to the corresponding carbon in ribose. Therefore, a modified mRNA can include nucleotides containing, for example, arabinose as a sugar. YANL / a / zuzz / uu i oou 110 Skeletal modifications Backbone phosphate groups can be modified by replacing one or more of the oxygen atoms with a different substituent. Additionally, modified nucleosides and nucleotides can include the complete replacement of an unmodified phosphate moiety with a modified phosphate as described herein. Examples of modified phosphate groups include, but are not limited to, phosphorothioate, phosphoroselenates, borane phosphates, borane phosphate esters, hydrogen phosphonates, phosphoramidates, alkyl or aryl phosphonates, and phosphotriasters. Phosphoradithioates have both non-bonding oxygens replaced with sulfur. The phosphate linker can also be modified by replacing an oxygen bond with nitrogen (bridged phosphoroamidates), sulfur (bridged phosphorothioates), and carbon (bridged methylene phosphonates). Lipid modifications A lipid-modified mRNA typically comprises an mRNA as defined herein. Such a lipid-modified mRNA, as defined herein, typically further comprises at least one linker covalently linked to that mRNA, and at least one lipid covalently linked to the respective linker. Alternatively, the lipid-modified mRNA comprises at least one mRNA as defined herein and at least one (bifunctional) lipid covalently linked (without a linker) to that mRNA. According to a third alternative, the lipid-modified mRNA comprises an mRNA molecule as defined herein, at least one linker covalently linked to that mRNA, and at least one lipid covalently linked to the respective linker, and also at least one (bifunctional) lipid covalently linked (without a linker) to that mRNA.In this context, it is particularly preferred that the lipid modification is present at the terminal ends of a linear mRNA sequence. In another preferred embodiment, the mRNA compound does not comprise nucleoside modifications, in particular base modifications. In a further embodiment, the mRNA compound does not comprise 1-methylpseudouridine, pseudouridine, or 5-methoxyuridine modifications. In a preferred embodiment, the mRNA comprises only naturally occurring nucleosides. In a further preferred embodiment, the mRNA compound does not comprise any chemical modifications and optionally comprises sequence modifications. In another preferred embodiment of the invention, the mRNA compound only comprises the naturally occurring nucleosides adenine, uracil, guanine, and cytosine. Basic modifications In an alternative embodiment, the mRNA compound comprises at least one base modification. Modified nucleosides and nucleotides, which can be incorporated into a modified mRNA compound comprising an mRNA sequence as described herein, can be further modified in the core base moiety. Examples of core bases found in mRNA include, but are not limited to, adenine, guanine, cytosine, and uracil. For example, nucleosides 111 and nucleotides described herein can be chemically modified on the face of the major groove. In some embodiments, the major chemical modifications of the groove can include an amino group, a thiol group, an alkyl group, or a halo group. In particularly preferred embodiments of the present invention, the nucleotide analogs / modifications are selected from base modifications, which are preferably selected from 2-amino-6-chloropurine riboside-5'-triphosphate, 2-aminopurine riboside-5'-triphosphate; 2'-aminoadenosine-5'-triphosphate, 2'-amino-2'-deoxycytidine-triphosphate, 2-thiocitidine-5'-triphosphate, 2-thiouridine-5'-triphosphate, 2'-fluorothymidine-5'-triphosphate, 2'-O-methyl-nosine-5'-triphosphate 4-thiouridine-5'-trif osf ato, 5-aminoallylcytidine-5'-triphosphate, 5-aminoallyluridine-5'-triphosphate, 5-bromocytidine-5'-triphosphate, 5-bromouridine-5'-triphosphate, 5-bromo-2'-deoxycytidine-5'-triphosphate, 5-bromo-2'-deoxyuridine-5'-triphosphate, 5-iodocytidine-5'triphosphate, 5-iodo-2'-deoxycytidine-5'-triphosphate, 5-iodoruridine-5'-triphosphate, Special preference is given to nucleotides for base modifications selected from the group of base-modified nucleotides consisting of 5-methylcytidine-5'-triphosphate,7-deazaguanosine-5'-triphosphate, 5-bromocytidine-5'-triphosphate and pseudouridine-5'-triphosphate. In some embodiments, the modified nucleosides include pyridin-4-one ribonucleoside, 5-azauridine, 2-thio-5-azauridine, 2-thiouridine, 4-thiopseudouridine, 2-thiopseudouridine, 5-hydroxyuridine, 3-methyluridine, 5-carboxymethyluridine, 1-carboxymethylpseudouridine, 5-propynyluridine, 1-propynylpseudouridine, 5-taurinomethyluridine, 1-taurinomethylpseudouridine, 5-taurinomethyl-2-thiouridine, 1-taurinomethyl-4-thiouridine, 5-methyluridine, 1-methylpseudouridine, 4-thio-1-methylpseudouridine, 2-thio-1-methylpseudouridine, 1-methyl-1-deaza-pseudouridine, 2-thio-1-methyl-1-deaza-pseudouridine, d hydra uridine, dihydropseudouridine, 2-thio-dihydrouridine, 2-thio-dihydropseudouridine, 2-methoxyuridine, 2-methoxy-4-thio-uridine, 4-methoxy-pseudouridine, and 4-methoxy-2-thio-pseudouridine. In some embodiments, the modified nucleosides include 5-aza-cytidine, pseudoisocytidine, 3-methyl-cytidine,N4-acetylcytidine, 5-formylcytidine, N4methylcytidine, 5-hydroxymethylcytidine, 1-methyl-pseudoisocytidine, pyrrolo-cytidine, pyrrolo-pseudoisocytidine, 2-thiocytidine, 2-thio-5-methyl-cytidine, 4-thio-pseudoisocytidine, 4-thio-1-methyl-pseudoisocytidine, 4-thio-1-methyl-pseudoisocytidine, 4-thio-1-methyl-1-deazapseudoisocytidine, 1-methyl-1-dezaza-pseudoisocytidine, zebularine, 5-aza-zebularina, 5-methyl-zebularina, 5-aza2-thio-zebularina, 2-thio-zebularina, 2-methoxy-cytidine, 2-methoxy-5-methyl-cytidine, 4-methoxy-pseudoisocytidine, and 4methoxy-1-methyl-pseudoisocytidine. In other modalities, the modified nucleosides include 2-aminopurina, 2, 6-diaminopurina, 7-deaza-adenina, 7-deaza-8-aza-adenina, 7-deaza-2-aminopurina, 7-deaza-8-aza-2aminopurina, 7-deaza-2,6-diaminopurina, 7-deaza-8-aza-2,6-diaminopurina, 1-metiladenosina, N6metiladenosina, N6-isopenteniladenosina, N6-(cis-h¡droxiisopenten¡l)adenosina, 2- metiltio-N6-(cishydroxyisopentenil) adenosina, N6-glicin¡lcarbamoiladenosina, N6-threonylcarbamoiladenosina,2-methylthio-N6threonyl carbamoyladenosine, N6,N6-dimethyladenosine, 7-methyladenine, 2-methylthio-adenine and 2-methoxyadenine. In other embodiments, modified nucleosides include inosine, 1-methyl-inosine, wyosine, wybutosine, 7-deaza-guanosine, 7-deaza-8-aza-guanosine, 6-thio-guanosine, 6-thio-7-deaza-guanosine, 6-thio-7-deaza-8-azaguanosine, 7-methyl-guanosine, 6-thio-7-methyl-guanosine, 7-methylinosine, 6-methoxy-guanosine, 1-methylguanosine, N2-methylguanosine, N2,N2-dimethylguanosine, 8-oxo-guanosine, 7-methyl-8-oxo-guanosine, 1-methyl-6-thioguanosine, N2-methyl-6-thio-guanosine, and N2,N2-dimethyl-6-thio-guanosine. In some embodiments, the nucleotide may be modified on the major groove face and may include hydrogen substitution at C-5 of uracil ινΐΛ / a / zuzz / uu / oou, 112 with a methyl group or a halo group. In specific embodiments, a modified nucleoside is 5'-O-(1-thiophosphate)-adenosine, 5'O-(1-thiophosphate)-cytidine, 5'O-(1-thiophosphate)-guanosine, 5'-O-(1-thiophosphate)-uridine, or 5'O-(1-thiophosphate)-pseudouridine, 1-methyl-6-thio-guanosine, N2-methyl-6-thio-guanosine, and N2,N2-dimethyl-6-thioguanosine. In some embodiments, the nucleotide can be modified on the major groove face and can include substitution of hydrogen at C-5 of uracil with a methyl group or a halo group. In specific embodiments, a modified nucleoside is 5'-O-(1-thiophosphate)-adenosine, 5'-O-(1-thiophosphate)-cytidine, 5'-O-(1-thiophosphate)-guanosine, 5'-O-(1-thiophosphate)-uhdine, or 5'-O-(1-thiophosphate)-pseudouridine, 1-methyl-6-thio-guanosine, N2-methyl-6-thio-guanosine, and N2,N2-dimethyl-6-thio-guanosine. In some embodiments, the nucleotide may be modified on the major groove face and may include substitution of hydrogen at C-5 of uracil with a methyl group or a halo group.In specific embodiments, a modified nucleoside is 5'-O-(1-thiophosphate)adenosine, 5'-O-(1-thiophosphate)-cytidine, 5'-O-(1-thiophosphate)-guanosine, 5'-O-(1-thiophosphate)-uridine, or 5'-O-(1-thiophosphate)-pseudouridine. In additional specific embodiments, a modified mRNA may comprise nucleoside modifications selected from 6-aza-cytidine, 2-thio-cytidine, α-thio-cytidine, pseudo-iso-cytidine, 5-aminoallyl-uridine, 5-yodo-uridine, N1-meth¡l-pseudour¡d¡na, 5,6-dihydrouridine, α-thio-uridine, 4-thio-uridine, 6aza-uridine, 5-hydroxy-uridine, deoxy-thymidine, 5-methyl-uridine, pyrrolo-cytidine, inosine, α-thio-guanosine, 6-methylguanosine, 5-methyl-cytdine, 8-oxo-guanosine, 7-deaza-guanosine, N1-methyl-adenosine, 2-amino-6-chloro-purine, N6-methyl-2-amino-purine, pseudo-iso-cytidine, 6-chloro-purine, N6-methyl-adenosine, α-thio-adenosine, 8-azidoadenosine, 7-deaza-adenosine. In further embodiments, the chemical modification is selected from pseudouridine, N1methylpseudouridine, N1-ethylpseudouridine, 2-thiouridine, 4'-thiouridine, 5-methylcytosine, 5-methyluridine, 2-thio-1methyl-1-deaza-pseudouridine, 2-thio-1-methyl-pseudouridine, 2-thio-5-aza-uridine, 2-thio-dihydropseudouridine, 2-thio-dihydrouridine, 2-thio-pseudouridine, 4-methoxy-2-thio-pseudouridine, 4-methoxy-pseudouridine, 4-thio-1 -methylpseudouridine, 4-thio-pseudouridine, 5-aza-uridine, dihydropseudouridine, 5-methoxyuridine and 2'-0-methyl uridine. In a specific embodiment, the chemical modification is selected from the group consisting of pseudouracil (ψ), N1-methylpseudouracil (N1Mψ), 1-ethylpseudouracil, 2-thiouracil (s2U), 4-thiouracil, 5-methylcytosine, 5-methyluracil, 5-methoxyuracil, and any combination thereof. Sequence modifications According to a further embodiment, the mRNA compound comprises a modified mRNA sequence. For example, a modification of the mRNA sequence may lead to stabilization of the mRNA sequence. In one embodiment, the mRNA compound comprises a stabilized mRNA sequence comprising at least one coding region as defined herein. In particular, the composition of the invention as described herein may comprise an mRNA compound comprising a coding region encoding a peptide or a protein, as defined in any of the embodiments described herein, wherein said coding region has a sequence modification. According to one embodiment, the mRNA compound comprises an mRNA sequence 113 stabilized, i.e. as an mRNA that is substantially resistant to degradation in vivo (e.g. by an exonuclease or endonuclease). Such stabilization can be effected, for example, by a modified phosphate backbone of the mRNA of the present invention. A backbone modification according to the present invention is a modification wherein the backbone phosphates of the nucleotides contained in the mRNA are chemically modified. Nucleotides that can preferably be used herein contain, for example, a phosphorothioate-modified phosphate backbone, preferably at least one of the phosphate oxygens contained in the phosphate backbone is replaced by a sulfur atom.Stabilized mRNAs may further include, for example: non-ionic phosphate analogues, such as, for example, alkyl and aryl phosphonates, wherein the charged phosphonate oxygen is replaced by an alkyl or aryl group, or phosphodiesters and alkylphosphotriesters, wherein the charged oxygen residue is present in alkylated form. Such backbone modifications typically include, but are not limited to, modifications from the group consisting of methylphosphonates, phosphoramidates, and phosphorothioates (e.g., cytidine-5'-O-(1-thiophosphate)). Specific modifications that are preferably capable of “stabilizing” mRNA as defined herein are described below. G / C Content Modifications According to one embodiment, the mRNA compound comprises an mRNA sequence that is modified and thus stabilized by a modification of its guanosine / cytosine (G / C) content. Such modification, or at least one of such modifications, is located within a coding region of the mRNA compound. In a preferred embodiment, the G / C content of the coding region of the mRNA compound is increased compared to the G / C content of the coding region of the respective wild-type mRNA, i.e., the unmodified mRNA. At the same time, the amino acid sequence encoded by the mRNA is preferably unmodified compared to the amino acid sequence encoded by the respective wild-type mRNA. For example, the composition described above may comprise an mRNA compound encoding a pathogenic antigen whose amino acid sequence is unmodified with respect to the encoded amino acid sequence of the respective wild-type nucleic acid. This modification of the mRNA sequence of the present invention is based on the fact that the sequence of any mRNA region to be translated is important for the efficient translation of that mRNA. Therefore, the composition of the mRNA and the sequence of several nucleotides are important. In particular, sequences having an increased G (guanosine) / C (cytosine) content are more stable than sequences having an increased A (adenosine) / U (uracil) content. According to the invention, the codons of the mRNA therefore vary compared to the respective wild-type mRNA, while retaining the translated amino acid sequence, such that they include an increased amount of G / C nucleotides. With regard to the fact that several codons code for the same amino acid (the so-called degeneracy of the genetic code), the most favorable codons for stability can be determined (the so-called alternative codon usage).Depending on the amino acid to be encoded by it. 114 mRNA, there are several possibilities for modifying the mRNA sequence compared to its wild-type sequence. In the case of amino acids encoded by codons containing exclusively G or C nucleotides, no codon modification is necessary. Thus, the codons for Pro (CCC or CCG), Arg (CGC or CGG), Ala (GCC or GCG), and Gly (GGC or GGG) do not require modification, since no A or U are present. In contrast, codons containing A and / or U nucleotides can be modified by substituting other codons that code for the same amino acids but do not contain A and / or U. Examples of these are: the codons for Pro can be modified from CCU or CCA to CCC or CCG; the codons for Arg can be modified from CGU or CGA or AGA or AGG to CGC or CGG; the codons for Ala can be modified from GCU or GCA to GCC or GCG; The codons for Gly can be modified from GGU or GGA to GGC or GGG.In other cases, although A or U nucleotides cannot be removed from codons, it is nevertheless possible to decrease the A and U content by using codons that contain a lower content of A and / or U nucleotides.Examples of these are: the codons for Phe can be changed from UUU to UUC; the codons for Leu can be changed from UUA, UUG, CULI, or CUA to CUC or CL)G; the codons for Ser can be changed from UCU or UCA or AGU to UCC, UCG, or AGC; the codon for Tyr can be changed from UAU to UAC; the codon for Cys can be changed from UGU to UGC; the codon for His can be changed from CAU to CAC; the codon for Gln can be changed from CAA to CAG; the codons for He can be changed from AUU or AUA to AUC; the codons for Thr can be changed from ACU or ACA to ACC or ACG; the codon for Asn can be changed from AAU to AAC; the codon for Lys can be changed from AAA to AAG; the codons for Val can be changed from GUU or GUA to GUC or GUG; The codon for Asp can be modified from GAU to GAC; the codon for Glu can be modified from GAA to GAG; the codon determining UAA can be modified to UAG or UGA. In the case of the codons for Met (AUG) and Trp (UGG), however, there is no possibility of sequence modification.The substitutions listed above may be used individually or in all possible combinations to increase the G / C content of the mRNA sequence of the present invention as compared to its particular wild-type mRNA (i.e., the original sequence). Thus, for example, all codons for Thr that appear in the wild-type sequence may be modified to ACC (or ACG). Preferably, however, for example, combinations of the above substitution possibilities are used: replacement of all codons encoding Thr in the original sequence (wild-type mRNA) to ACC (or ACG) and replacement of all codons originally encoding Ser to UCC (or UCG or AGC); replacement of all codons encoding lie in the original sequence with AUC and replacement of all codons originally encoding Lys with AAG and replacement of all codons originally encoding Tyr with UAC; replacement of all codons encoding Val in the original sequence with GUC (or GUG) and replacement of all codons originally encoding Glu with GAG and ινΐΛ / a / zuzz / uu / oou 115 and replacement of all codons originally coding for Ala with GGG (or GGG) replacement of all codons originally coding for Arg with GGG (or GGG); replacement of all codons coding for Val in the original sequence with GUG (or GUG) and replacement of all codons originally coding for Glu with GAG and replacement of all codons originally coding for Ala with GGG (or GGG) replacement of all codons originally coding for Gly with GGG (or GGG) and replacement of all codons originally coding for Asn with AAC;replacement of all codons coding for Val in the original sequence with GUC (or GUG) and replacement of all codons originally coding for Phe with UUC and replacement of all codons originally coding for Cys with UGC and replacement of all codons originally coding for Leu with GUG (or CUC) and replacement of all codons originally coding for Gln with CAG and replacement of all codons originally coding for Pro with CCC (or CCG); etc. Preferably, the G / C content of the coding region of the mRNA compound that; IVIA / a / ZUZZ / UU l oou comprises an mRNA sequence of the present invention is increased by at least 7%, more preferably at least 15%, particularly preferably at least 20%, compared to the G / C content of the coding region of the wild-type RNA, encoding an antigen as defined herein or a fragment or variant thereof. According to a specific embodiment, at least 5%, 10%, 20%, 30%, 40%, 50%, 60%, more preferably at least 70%, even more preferably at least 80% and most preferably at least 90%, 95% or even 100% of the substitutable codons in the region encoding a peptide or protein as defined herein or a fragment or variant thereof or the entire sequence of the wild-type mRNA sequence are substituted, thereby increasing the G / C content of said sequence.In this context, it is particularly preferable to increase the G / C content of the mRNA sequence of the present invention, preferably of at least one coding region of the mRNA sequence according to the invention, to the maximum (i.e., 100% of the substitutable codons) as compared to the wild-type sequence. According to the invention, another preferred modification of the mRNA sequence of the present invention is based on the discovery that translation efficiency is also determined by a different frequency in the occurrence of tRNAs in cells. Therefore, if so-called "rare codons" are present in the mRNA sequence of the present invention to a greater extent, the corresponding modified mRNA sequence is translated to a significantly lower extent than in the case where codons encoding relatively "frequent" tRNAs are present. According to the. 116 invention, in the modified mRNA sequence of the present invention, the region encoding a peptide or protein as defined herein or a fragment or variant thereof is modified compared to the corresponding region of the wild-type mRNA sequence such that at least one codon of the wild-type mRNA sequence, which encodes a tRNA that is relatively rare in the cell, is exchanged with a codon, which encodes a tRNA that is relatively frequent in the cell and carries the same amino acid as the relatively rare tRNA. By this modification, the mRNA sequence of the present invention is modified such that codons are inserted for which frequent tRNAs are available.In other words, according to the invention, by means of this modification, all codons of the wild-type sequence, which code for a tRNA that is relatively rare in the cell, can be exchanged in each case for a codon, which codes for a tRNA that is relatively frequent in the cell and which, in each case, carries the same amino acid as the relatively rare tRNA. Which tRNAs occur relatively frequently in the cell and which, on the contrary, occur relatively rarely are known to the person skilled in the art; cf. for example, Akashi, Curr. Gineta Opinion. Development 2001, 11(6): 660-666. Particularly preferred are codons, which use the most frequently occurring tRNA for the particular amino acid, for example, the codon Gly, which is used by the tRNA, which occurs most frequently in the (human) cell.According to the invention, it is particularly preferable to link the sequential G / C content which is increased, in particular maximized, in the modified mRNA sequence of the present invention, to the “frequent” codons without modifying the amino acid sequence of the protein encoded by the coding region of the mRNA sequence. This preferred embodiment allows the provision of a particularly efficient translated and stabilized (modified) mRNA sequence of the present invention. The determination of a modified mRNA sequence of the present invention as described above (increased G / C content; tRNA exchange) can be carried out using the computer program explained in WO02 / 098443, the disclosure content of which is included in its full scope, in the present invention.Using this computer program, the nucleotide sequence of any desired mRNA sequence can be modified with the help of the genetic code or the degenerative nature thereof in such a way that a maximum G / C content results, in combination with the use of codons encoding tRNAs that occur as frequently as possible in the cell, the amino acid sequence encoded by the modified mRNA sequence preferably being unchanged compared to the unmodified sequence. Alternatively, it is also possible to modify only the G / C content or only the codon usage compared to the original sequence. The Visual Basic 6.0 source code (development environment used: Microsoft Visual Studio Enterprise 6.0 with Service Pack 3) is also described in WO02 / 098443.In another preferred embodiment of the present invention, the A / U content in the vicinity of the ribosome binding site of the mRNA sequence of the present invention is increased compared to the A / U content in the vicinity of the ribosome binding site of its respective wild-type mRNA sequence. This modification (a higher A / U content around the ribosome binding site) increases the efficiency of ribosome binding to the mRNA. Efficient binding of ribosomes to the ribosome binding site (Kozak sequence: SEQ ID NO: 1 or SEQ ID NO: 2, or a minimal Kozak sequence ACO, wherein AUG forms the start codon) in turn has the effect of efficient translation of the mRNA. According to a further embodiment. 117 of the present invention, the mRNA sequence of the present invention may be modified with respect to potentially destabilizing sequence elements. In particular, the coding region and / or the 5' and / or 3' untranslated region of this mRNA sequence may be modified compared to the respective wild-type mRNA such that it does not contain destabilizing sequence elements, the encoded amino acid sequence of the modified mRNA sequence is preferably not modified compared to its respective wild-type mRNA. It is known that, for example, in eukaryotic mRNA sequences, destabilizing sequence elements (DSEs) occur, to which signal proteins bind and regulate the enzymatic degradation of mRNA in vivo.For further stabilization of the modified mRNA sequence, optionally in the region encoding at least one peptide or protein as defined herein or a fragment or variant thereof, one or more such modifications may be made compared to the corresponding region of the wild-type mRNA, such that it does not contain or substantially no destabilizing sequence elements. According to the invention, DSE present in the untranslated regions (3'- and / or 5'-UTR) may also be eliminated from the mRNA sequence of the present invention by such modifications. Such destabilizing sequences are, for example, ALI-rich sequences (AURES), which occur in 3'-UTR sections of numerous unstable mRNAs (Caput et al., Proc. Nati. Acad. Sci. USA 1986, 83: 1670-1674).Therefore, the mRNA sequence of the present invention is preferably modified compared to the respective wild-type mRNA such that the mRNA sequence of the present invention does not contain such destabilizing sequences. This also applies to those sequence motifs that are recognized by potential endonucleases, for example, the sequence GAACAAG, which is contained in the 3'-UTR segment of the gene encoding the transerrin receptor (Binder et al., EMBOJ. 1994, 13: 1969-1980). These sequence motifs are also preferably eliminated in the mRNA sequence of the present invention. According to a further embodiment, the mRNA compound comprises an mRNA sequence comprising a coding region comprising or consisting of any of the RNA sequences as described in Tables 1-5, Figures 20-24 or in the sequence listing of WO 2018 / 078053; Tables 1-5 or Figures 20-24 of WO 2018 / 078053; WO 2018 / 078053 incorporated by reference in its entirety. Sequences adapted to human codon usage Another preferred modification of the mRNA compound is based on the finding that codons encoding the same amino acid normally occur at different frequencies. According to this embodiment, the frequency of codons encoding the same amino acid in the coding region of the mRNA compound differs from the natural frequency of that codon according to human codon usage as, for example, shown in Table 2 (Human Codon Usage Table). For example, in the case of the amino acid alanine (Ala), the wild-type coding region is preferably adapted so that the codon “GCC” is used with a frequency of 0.40, the codon “GCT” is used with a frequency of 0.28, the codon “GCA” is used with a frequency of 0.22 and the codon “GCG” is used with a frequency of 0.10 etc. (see Table 2). YANL / a / zuzz / uu i oou 118 Table 2: Human codon usage table, the most frequent codons are marked with asterisks. Amino Acid Codon Fraction / 1000 GCG Ala 0.10 7.4 GCA Ala 0.22 15.8 GCT Ala 0.28 18.5 GCC* Ala 0.40 27.7 Cys TGT 0.42 10.6 Cys TGC* 0.58 As GAT 12.6 0.56 25.1 Glu GAG* 0.59 39.6 Glu GAA 0.41 29.0 Phe TTT 0.43 17.6 Phe TTC* 0.57 20.3 Gly GGG 0.23 16.5 Gly GGA 0.28 Gly Gly 16.5 0.33 22.2 His CAT 0.41 10.9 His CAC* 0.59 15.1 lie ATA 0.14 7.5 He ATT 0.35 16.0 He ATC* 0.52 20.8 Lys AAG* 0.60 A2 31.9 0.4 Lys AAG* 0.60 A2 31.9 0.4 12.9 Leu TTA 0.06 7.7 Leu CTG* 0.43 39.6 Leu CTA 0.07 7.2 Leu CTT 0.12 13.2 Leu CTC 0.20 19.6 Met ATG* 1 22.0 Asn 11 AAT 0.4 *most frequent codon Amino Acid Codon Fraction / 1000 Pro CCG 0.11 6.9 Pro CCA 0.27 16.9 Pro CCT 0.29 17.5 Pro CCC* 0.33 19.8 Gln CAG* 0.73 34.2 Gln CAA 0.27 12.3 Arg AGG 0.22 12.0 Arg AGA* 0.21 12.1 Arg CGG 0.19 11.4 Arg CGA 0.10 6.2 Arg CGT 0.09 4.5 Arg CGC 0.19 10.4 Ser AGT 0.14 12.1 Ser AGC* 0.25 19.5 Ser TCG 0.06 4.4 Ser TCA 0.15 12.2 Ser TCT 0.18 15.2 Ser TCC 0.23 17.7 Thr ACG 0.12 6.1 Thr ACA 0.27 15.1 Thr ACT 0.23 13.1 Thr ACC* 0.38 18.9 Val GTG* 0.48 28.1 Val GTA 0.10 7.1 Val GTT 0.17 11.0 Val GTC 0.25 14.5 Trp TGG* 1 13.2 Tyr TAT 0.42 12.2 Tyr TAC* 0.58 15.3 Stop TGA* 0.61 1.6 Stop TAG 0.17 0.8 Stop TAA 0.22 1.0 Codon-optimized sequences In one embodiment, all codons in the wild-type sequence that encode a tRNA, which is relatively rare in the cell, are exchanged for one codon that encodes a tRNA, which is relatively frequent in the cell and which, in each case, carries the same amino acid as the relatively rare tRNA. Therefore, it is particularly preferred that the most frequent codons for each amino acid be used. 119 encoded (see Table 2). Such an optimization method increases the codon adaptation index (CAI) and ultimately maximizes the CAI. In the context of the invention, sequences with increased or maximized CAI are typically referred to as “codon-optimized” sequences and / or increased and / or maximized CAI sequences. According to a preferred embodiment, the mRNA compound comprising an mRNA sequence of the present invention comprises at least one coding region, wherein the coding region / sequence is codon-optimized as described herein. More preferably, the codon adaptation index (CAI) of at least one coding sequence is at least 0.5, at least 0.8, at least 0.9, or at least 0.95. Most preferably, the codon adaptation index (CAI) of at least one coding sequence is 1. For example, in the case of the amino acid alanine (Ala) present in the amino acid sequence encoded by at least one coding sequence of the RNA according to the invention, the wild-type coding sequence is adapted such that the most frequent human codon “GCC” is always used for said amino acid, or for the amino acid Cysteine ​​(Cys), the wild-type sequence is adapted such that the most frequent human codon “TGC” is always used for said amino acid, etc. C-optimized sequences According to another embodiment, the mRNA compound comprises an mRNA sequence having a modified, in particular increased, cytosine (C) content of the coding region of the mRNA sequence, preferably compared to the C content of the coding region of the respective wild-type mRNA, i.e., the unmodified mRNA. At the same time, the amino acid sequence encoded by at least one coding region of the mRNA sequence of the present invention is preferably not modified compared to the amino acid sequence encoded by the respective wild-type mRNA. In a preferred embodiment of the present invention, the modified mRNA sequence is modified such that at least 10%, 20%, 30%, 40%, 50%, 60%, 70% or 80%, or at least 90% of the theoretically possible maximum cytosine content or even a maximum cytosine content is reached. In further preferred embodiments, at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90% or even 100% of the codons in the wild-type sequence of the target mRNA, which are “cytosine content optimized,” are replaced by codons having a higher cytosine content than those present in the wild-type sequence. In a further preferred embodiment, some of the codons in the wild-type coding sequence may be further modified such that a codon for a rela...

Claims

1. A cationic lipid according to formula (I): Ra-A-Rb formula (I) or a pharmaceutically acceptable salt, prodrug or stereoisomer thereof, wherein Ra is selected from: O 0 0 5 1 0 o 0 , or -R'-N(H)-C(O)-R3-R4; Rb is selected from: ° oo -R1-N(H)-C(O)-R3-R4, or -R1-N(CH3)2; A is -S-, -SS-, -NH-C(O)-, -NH-C(O)O-, -NH-C(O)-NH-, -SC(O)-N(H)-, C(O)O-, or -OP(O)(OH)-O-; R1 is a linear or unbranched ethanedyl, propanedyl, butanedyl, or alkanedyl having 2 to 8 carbon atoms, wherein each substitutable carbon atom is unsubstituted or substituted with one or more C1-C4 alkyl, C1-C4 alkenylene, C3-C8 cycloalkylene, or C3-C8 cycloalkenylene; R2 is an alkanedyl having 2 to 8 carbon atoms; R3 is optional, and if present, is -R5-C(O)-O-, -R5-OC(O)-, -R5-C(O)-NH-, -R5-OC(O)-NH-, or R5-NH-C(O)O-;R4 is a lipophilic substituent having 12 to 36 carbon atoms, wherein the lipophilic substituent having 12 to 36 carbon atoms is either (i) a linear or branched alkyl or alkenyl having 12 to 25 carbon atoms or (ii) a derivative of tocopherol or tocothreinol; R5 is an alkanedyl having 1 to 6 carbon atoms; X is a carbon atom bonded to a hydrogen atom (CH) or a nitrogen atom; wherein all selections are independent of each other. 258; 2. The cationic lipid according to claim 1, wherein R4 is either (i) a linear or branched alkyl or alkenyl having 12 to 25 carbon atoms or (ii) selected from the group of tocopherol and tocothreinol derivatives shown in Scheme 1.

3. The cationic lipid according to claim 1 or claim 2, wherein R4 is independently selected at each occurrence from the group consisting of IVIA / a / ZUZZ / UU l oou 4. The cationic lipid according to any one of claims 1 to 3, provided that if (i) R3 is present as -R5-C(O)-O- (i) R1 and R2 are linear unsubstituted ethanedyl, (i¡¡) R5 is either linear unsubstituted ethanedyl, linear unsubstituted propanedyl or linear unsubstituted butanedyl, (iv) A is -SS-, and (v) Ra and Rb are identical, then R4 is not and further provided that (i) R3 is absent, (i) R1 and R2 are linear unsubstituted ethanedyl, (iii) A is -SS-, and (iv) Ra and Rb are identical, then R4 is not and 5. The cationic lipid according to any one of claims 1 to 3, wherein A is -S-.

6. The cationic lipid according to claim 1 or claim 2, wherein R3 is present and is selected from the group consisting of -R5-C(O)-O-, -R5-OC(O)-, -R5C(O)-NH-, -R5-OC(O)-NH-, and R5-NH-C(O)O-; and R4 is a linear or branched alkyl or alkenyl having 12 to 25 carbon atoms.

7. The cationic lipid according to any one of claims 1 to 6, wherein Ra and Rb are independently selected from 0, with X being CH or -R1-N(H)C(O)-R3-R4.

8. The cationic lipid according to any one of claims 1 to 7, wherein each of Ra and Rb is: or with X being CH; and R3 is present and R5 is an alkanedyl having 2 to 6 carbon atoms, independently selected at each occurrence.

9. The cationic lipid according to any one of claims 1 to 8, wherein R3 is present and is -R5-C(O)-O- or -R5-OC(O)-, preferably -R5-C(O)-O-; R4 is: h3c . and wherein Ra and Rb are identical.

10. The cationic lipid according to any one of claims 1 to 8, wherein R3 is present and is -R5-C(O)-O- or -R5-OC(O)-, preferably -R5-C(O)-O-; R4 is: and wherein Ra and Rb are identical; 11. The cationic lipid according to claim 7 or 8, wherein R1 is ethanedyl.

12. The cationic lipid of any one of the preceding claims, further exhibiting one or more of the following features, independently selected at each occurrence: (i) R1 is an unsubstituted ethanedyl, propanedyl, or butanedyl; (ii) R2 is a linear, unbranched alkanedyl having 2 to 8 carbon atoms; (iii) R3 is -R5-C(O)-O- or -R5-OC(O)-; (iv) R5 is an alkanedyl having 2 to 6 carbon atoms; and / or (vi) X is CH.

13. The cationic liquid according to claim 1, which is selected from one of the compounds as listed in Table 1.

14. A composition comprising (i) the cationic lipid according to any one of claims 1 to 14; (ii) the C15 cationic lipid as listed in Table 1; (iii) the C2 cationic lipid as listed in Table 1; or (iv) the C26 cationic lipid as listed in Table 1. preferably, it further comprises one or more of the following excipients: (i) a steroid, preferably cholesterol; (iii) a neutral lipid; wherein said neutral lipid is preferably 1,2-diphthanol-sn-glycero-3-phosphoethanolamine (DPhyPE), optionally in combination with the neutral lipid 1,2-diheptanoyl-sn-glycero-3-phosphocholine (DHPC);or wherein said neutral lipid is a zwitterionic compound, optionally a zwitterionic compound having two fatty acid moieties selected from myristoyl, palmitoyl, stearoyl and oleol, in combination with a zwitterionic compound having two fatty acid moieties selected from pentanoyl, hexanoyl, heptanoyl, octanoyl, nonaoyl and decanoyl; and / or (iii) a polymer-conjugated lipid; wherein said polymer-conjugated lipid is a compound according to formula (II): PAL formula (II); wherein P is a hydrophilic polymer moiety, A is an optional linker and L is a lipid moiety; preferably where the polymer-conjugated lipid is a pegylated lipid; 15. A composition comprising one or more of the following excipients: (i) a cationic lipid according to any one of claims 1 to 13 or a cationic lipid comprising a tertiary or quaternary nitrogen / amino group or a cationic lipid carrying a net positive charge at physiological pH; (ii) a steroid, preferably cholesterol; (iii) a neutral lipid as described in sub-item (ii) according to claim 14; and / or (iv) a polymer-conjugated lipid, wherein said polymer-conjugated lipid is a compound according to formula (II): PAL formula (II); wherein P is a hydrophilic polymer moiety, A is an optional linker and L is a lipid moiety; preferably wherein the polymer-conjugated lipid is a pegylated lipid; more preferably, wherein the lipid fraction L comprises at least one fatty acid (“tail”) comprising 10 or 12 carbon atoms, preferably 8 or 10 carbon atoms;even more preferably, wherein the pegylated lipid is selected from the group consisting of 1,2-d-capryl-rac-glycero-3-methylpolyoxyethylene glycol 2000 (Cw-PEG 2000); and N-octanoyl-sphingosine-1{succinyl[methoxy(polyethylene glycol)2000]} (Cer8-PEG 2000).; 16. A composition comprising one or more of the following excipients: (i) a cationic lipid as described in item (i) of claim 17; (ii) a spheroid, preferably cholesterol;(iii) a neutral lipid as described in point (i) of claim 14, or preferably a combination of two neutral lipids wherein the combination comprises a neutral lipid or phospholipid having at least two alkyl chains, wherein each alkyl chain independently has a length of preferably C1, C2, C3, C4 or C5, more preferably with a length of C1, C2, C3, most preferably with a length of C2, more preferably a phospholipid selected from the group consisting of DHPC (1,2-diheptanoyl-sn-glycero-3-phosphocholine), O5:0 PC (1,2-dipentanoyl-sn-glycero-3-phosphocholine), O4:0 PC (1,2-dibutyryl-sn-glycero-3-phosphocholine), O6:0 PC (DHPC, 1,2-dihexanoyl-sn-glycero-3-phosphocholine), 08:0 PC (1,2-dioctanoyl-sn-glycero-3-phosphocholine) and 09:0 PC (1,2-dinonanoyl-sn-glycero-3-phosphocholine); and / or (iv) a polymer-conjugated lipid, wherein said polymer-conjugated lipid is a compound according to formula (II): PAL formula (II);wherein P is a hydrophilic polymer moiety, A is an optional linker, and L is a lipid moiety; preferably wherein the polymer-conjugated lipid is a pegylated lipid; more preferably wherein the pegylated lipid is 1,2-dimyristoyl-rac-glycero-3-methoxypolyethylene glycol 2000 (DMG-PEG 2000).

17. The composition according to any one of claims 14 to 16, wherein the composition comprises excipients in a proportion selected from the group consisting of (a-i) the cationic lipid in an amount of 30-70 mol%; the steroid in an amount of 20-50 mol%; the neutral lipid in an amount of 5-25 mol%; and the polymer-conjugated lipid IVIA / a / ZUZZ / UU l oou 262 in an amount of 0.5-5 mol%; (a-ii) the cationic lipid in an amount of 40-70 mol%; the steroid in an amount of 20-50 mol%; the neutral lipid in an amount of 5-15 mol%; and the polymer-conjugated lipid in an amount of 0.5-5 mol%; (a-¡¡¡) the cationic lipid in an amount of 20-60 mol%; the steroid in an amount of 25-55 mol%; the phospholipid in an amount of 5-25 mol%; and the polymer-conjugated lipid in an amount of 0.5-15 mol%; (a-iv) the cationic lipid in an amount of 45-65 mol%;the steroid in an amount of 25-45 mol%; the phospholipid in an amount of 8-12 mol%; and the polymer-conjugated lipid in an amount of 1-3 mol%; (av) the cationic lipid in an amount of 45-65 mol%; cholesterol in an amount of 25-45 mol%; the neutral lipid in an amount of 8-12 mol%; and the polymer-conjugated lipid in an amount of 1-3 mol%; (av¡) the cationic lipid in an amount of 45-65 mol%; cholesterol in an amount of 25-45 mol%; DPhyPE in an amount of 8-12 mol% and optionally DHPC in an amount of 1 to 10 mol%; and the polymer-conjugated lipid in an amount of 1-3 mol%; and (av¡) the cationic lipid in an amount of 45-65 mol%; cholesterol in an amount of 25-45 mol%; DPhyPE in an amount of 8-12 mol% and optionally DHPC in an amount of 1 to 10 mol%; and PEG-DMG 2000 in an amount of 1-3 mol%;or more preferably, the composition comprises excipients in a proportion selected from the group consisting of (bi) the cationic lipid in an amount of 59 mol%; the steroid in an amount of 29.3 mol%; the neutral lipid in an amount of 10 mol%; and the polymer-conjugated lipid in an amount of 1.7 mol%; (b-¡¡) the cationic lipid in an amount of 59 mol%; cholesterol in an amount of 29.3 mol%; the neutral lipid in an amount of 10 mol%; and the polymer-conjugated lipid in an amount of 1.7 mol%; (b-ili) the cationic lipid in an amount of 59 mol%; cholesterol in an amount of 29.3 mol%; DPhyPE in an amount of 10 mol%; and the polymer-conjugated lipid in an amount of 1.7 mol%; (b-iv) the cationic lipid in an amount of 59 mol%; cholesterol in an amount of 29.3 mol%; DPhyPE in an amount of 10 mol%; and C10-PEG 2000 in an amount of 1.7%;(bv) the cationic lipid in an amount of 59 mol%; cholesterol in an amount of 29.3 mol%; DPhyPE in an amount of 10 mol%; and Cer8-PEG 2000 in an amount of 1.7%; (bv¡) the cationic lipid in an amount of 59 mol%; the steroid in an amount of 28.3 mol%; the neutral lipid in an amount of 11 mol%; and the polymer-conjugated lipid in an amount of 1.7 mol%; (b-vii) the cationic lipid in an amount of 59 mol%; cholesterol in an amount of 28.3 mol%; the neutral lipid in an amount of 11 mol%; and the polymer-conjugated lipid in an amount of 1.7 mol%; (b-viii) the cationic lipid in an amount of 59 mol%; cholesterol in an amount of 28.3 mol%; DPhyPE in an amount of 10 mol% and DHPC in an amount of 1 mol%; and the polymer-conjugated lipid in an amount of 1.7 mol%; (b-ix) the cationic lipid in an amount of 59 mol%;cholesterol in an amount of 28.3 mol%; DPhyPE in an amount of 10 mol% and DHPC in an amount of 1 mol%; and C10-PEG 2000 in an amount of 1.7%; and (bx) the cationic lipid in an amount of 59 mol%; cholesterol in an amount of 28.3 mol%; DPhyPE in an amount of 10 mol% and DHPC in an amount of 1 mol%; and Cer8-PEG 2000 in an amount of 1.7%; (b-xi) the cationic lipid in an amount of 49 mol%; the steroid in an amount of 29.3 mol%; the neutral lipid in an amount of 20 mol%; and the polymer-conjugated lipid in an amount of 1.7%; (b-xii) the cationic lipid in an amount of 49 mol%; cholesterol in an amount of 29.3 mol%; the neutral lipid in an amount of 20 mol%; and the polymer-conjugated lipid in an amount of 1.7 mol%; (b-xiii) the cationic lipid in an amount of 49 mol%; cholesterol in an amount of 29.3 mol%;DPhyPE in an amount of 10 mol% and DHPC in an amount of 10 mol%; and the polymer-conjugated lipid in an amount of 1.7 mol%; (b-xiv) the cationic lipid in an amount of 49 mol%; cholesterol in an amount of 29.3 mol%; DPhyPE in an amount of 10 mol% and DHPC in an amount of 10 mol%; and Cw-PEG 2000 in an amount of 1.7%; and (b-xv) the cationic lipid in an amount of 49 mol%; cholesterol in an amount of 29.3 mol%; DPhyPE in an amount of 10 mol% and DHPC in an amount of 10 mol%; and Cer8-PEG 2000 in an amount of 1.7%; each quantity being relative to the total molar quantity of all lipid excipients of the lipid nanoparticles;more preferably, the composition comprises excipients in a proportion selected from the group consisting of (c-¡) a combination of lipid excipients selected from the group consisting of E1 to E108 as described in Table E in molar percentages selected from the group consisting of F1 to F62 as described in Table F; wherein preferably the composition comprises excipients in a proportion of (i) 59 mol % of C23 cationic lipid (COATSOME® SS-EC) as described in Table 1, 29.3 mol % of cholesterol, 10 mol % of DPhyPE and 1.7 mol % of DMG-PEG 2000; (i) 59 mol % cationic lipid C2 as described in Table 1, 29.3 mol % cholesterol, 10 mol % DPhyPE and 1.7 mol % DMG-PEG 2000;(iii) 59 mol % C15 cationic lipid as described in Table 1, 29.3 mol % cholesterol, 10 mol % DPhyPE and 1.7 mol % DMG-PEG 2000. (iv) 59 mol % C26 cationic lipid as described in Table 1, 29.3 mol % cholesterol, 10 mol % DPhyPE and 1.7 mol % DMG-PEG 2000; (v) 59 mol % C23 cationic lipid (COATSOME® SS-EC) as described in Table 1, 28.3 mol % cholesterol, 10 mol % DPhyPE, 1 mol % DHPC and 1.7 mol % DMGPEG 2000; (vi) 59 mol % C2 cationic lipid as described in Table 1, 28.3 mol % cholesterol, 10 mol % DPhyPE, 1 mol % DHPC and 1.7 mol % DMG-PEG 2000; (vii) 59 mol % C15 cationic lipid as described in Table 1, 28.3 mol % cholesterol, 10 mol % DPhyPE, 1 mol % DHPC and 1.7 mol % DMG-PEG 2000;(viii) 59 mol % C26 cationic lipid as described in Table 1, 28.3 mol % cholesterol, 10 mol % DPhyPE, 1 mol % DHPC and 1.7 mol % DMG-PEG 2000; (ix) 49 mol % C23 cationic lipid (COATSOME® SS-EC) as described in Table 1, 29.3 mol % cholesterol, 10 mol % DphyPE. 10 mol % DHPC and 1.7 mol % DMG-PEG 2000; (x) 49 mol % C2 cationic lipid as described in Table 1, 29.3 mol % cholesterol, 10 mol % DPhyPE, 10 mol % DHPC and 1.7 mol % DMG-PEG 2000; (xi) 49 mol % C15 cationic lipid as described in Table 1, 29.3 mol % cholesterol, 10 mol % DPhyPE, 10 mol % DHPC and 1.7 mol % DMG-PEG 2000; or (xii) 49 mol % C26 cationic lipid as described in Table 1, 29.3 mol % cholesterol, 10 mol % DPhyPE, 10 mol % DHPC and 1.7 mol % DMG-PEG 2000; 18. The composition according to any one of claims 14 to 17, further comprising a biologically active ingredient; wherein the biologically active ingredient is preferably a nucleic acid compound selected from the group consisting of an artificial mRNA, chemically modified or unmodified messenger RNA (mRNA) comprising at least one coding sequence, self-replicating RNA, circular RNA, viral RNA, and replicon RNA; or any combination thereof, more preferably wherein the biologically active ingredient is an mRNA or an mRNA compound.

19. The composition according to any one of claims 14 to 18, wherein the lipid nanoparticles comprise the mRNA (I) in an amount such that a N / P ratio in the range of 10 to 20 is achieved; or (II) in an amount such that a lipid:mRNA weight ratio in the range of 20 to 60 is achieved, preferably from about 3 to about 15, from 5 to about 13, from about 4 to about 8, or from about 7 to about 11; and / or wherein the composition is a sterile solid composition for reconstitution with a sterile liquid carrier, and wherein the composition further comprises one or more inactive ingredients selected from pH modifying agents, bulking agents, stabilizers, nonionic surfactants, and antioxidants, and wherein the sterile liquid carrier is an aqueous vehicle;and / or wherein the composition is a sterile liquid composition, and wherein the lipid nanoparticles have a mean hydrodynamic diameter determined by dynamic laser scattering of about 50 nm to about 300 nm, or about 60 nm to about 250 nm, or about 60 nm to about 200 nm, or about 70 to 200 nm, or about 75 nm to about 160 nm, or about 90 nm to about 140 nm, or about 100 nm to about 140 nm; and / or wherein the lipid nanoparticles exhibit a zeta potential in the range of -50 mV to +50 mV.; 20. The composition according to any one of claims 18 to 19, wherein the mRNA compound is a mono-, bi-, or multicistronic mRNA; or wherein the mRNA compound comprises at least one chemical modification; wherein the chemical modification is preferably selected from the group consisting of base modifications, sugar modifications, backbone modifications, and lipid modifications, more preferably wherein the chemical modification is a base modification, more preferably wherein the base modification is selected from the group consisting of pseudouracil (ψ), Nl-methylpseudouracil (N1Mψ), 1-ethylpseudouracil, 2-thiouracil (s2U), 4-thiouracil, 5-methylcytosine, 5-methyluracil, 5-methoxyuracil, and any combination thereof.

21. The composition according to any one of claims 18 to 20, wherein the mRNA compound comprises a coding region encoding a peptide or a protein, wherein the coding region exhibits a sequence modification; wherein the sequence modification is preferably selected from a G / C content modification, a codon modification, a codon optimization, or a C optimization of the sequence; more preferably wherein - the G / C content of the coding region is increased; - the C content of the coding region is increased; - the codon usage in the coding region is adapted to human codon usage; and / or the codon adaptation index (CAI) is increased or maximized in the coding region compared to the coding region of the corresponding wild-type mRNA.

22. The composition according to any one of claims 18 to 21, wherein the mRNA compound further comprises a) a 5'-CAP structure; b) at least one miRNA sequence, preferably wherein the microRNA binding site is for a microRNA selected from the group consisting of miR-126, miR-142, miR-144, miR-146, miR-150, miR-155, miR-16, miR-21, miR-223, miR-24, miR-27, miR-26a or any combination thereof; c) at least one 5'-UTR element; d) at least one poly(A) sequence; e) at least one poly(C) sequence; f) at least one 3'-UTR element; or any combination thereof; and / or wherein the at least one coding RNA comprises a 5'-CAP structure, preferably m7G, CAPO, CAP1, CAP2, a modified CAPO or a modified CAP1 structure;and / or wherein at least one coding RNA comprises at least one heterologous 5'-UTR and / or at least one heterologous 3'-UTR, preferably wherein at least one heterologous 5'-UTR comprises a nucleic acid sequence derived from a 5'-UTR of a gene selected from HSD17B4, RPL32, ASAH1, ATP5A1, MP68, NDUFA4, NOSIP, RPL31, SLC7A3, TUBB4B and UBQLN2, or from a homolog, fragment or variant according to any of these genes; and / or preferably wherein at least one heterologous 3'-UTR comprises a nucleic acid sequence derived from a 3'-UTR of a gene selected from PSMB3, ALB7, alpha-globin, CASP1, COX6B1, GNAS, NDUFA1 and RPS9, or from a homolog, fragment or variant of any of these genes; and / or wherein the at least one coding RNA comprises a (i) HSD17B4 5'-UTR and a PSMB3 3'-UTR or (i) a RPL32 5'-UTR and an ALB7 3'-UTR;and / or comprising the following elements in the 5' to 3' direction: a) a 5'-CAP structure, preferably selected from the group consisting of m7G(5'), m7G(5jppp(5j(2'OMeA) and m7G(5jppp(5j(2OMeG); b) a 5'-UTR element comprising a nucleic acid sequence derived from the 5'UTR of a TOP gene, said nucleic acid sequence preferably comprising an RNA sequence corresponding to the nucleic acid sequence according to SEQ ID NO:22, 24, 26, or a homolog, a fragment or a variant thereof; c) at least one coding sequence; d) a 3'-UTR element comprising a nucleic acid sequence derived from an α-globin gene, said nucleic acid sequence preferably comprising an RNA sequence corresponding to the nucleic acid sequence according to SEQ ID NO:6, 8, 10, 12, 14, 16, 18, 20, or a homolog, fragment or variant thereof;and / or a 3'-UTR element comprising a nucleic acid sequence derived from an albumin gene, said nucleic acid sequence preferably comprising an RNA sequence corresponding to the nucleic acid sequence according to SEQ ID NO:18, or a homolog, fragment or variant thereof; e) optionally, at least one poly(A) sequence, preferably consisting of 10 to 200, 10 to 100, 40 to 80 or 50 to 70 adenosine nucleotides; f) optionally, at least one poly(C) sequence, preferably consisting of 10 to 200, 10 to 100, 20 to 70, 20 to 60 or 10 to 40 cytosine nucleotides; and g) optionally, at least one histone stem-loop, preferably comprising the RNA sequence according to SEQ ID NO:4;and / or wherein the biologically active ingredient is (a) an mRNA comprising at least one coding sequence encoding a peptide or a protein, or a fragment or variant thereof, wherein the peptide or protein is an antigen, wherein the antigen is preferably derived from pathogenic antigens, tumor antigens, allergenic antigens or autoimmune autoantigens, or a fragment or variant thereof; or (b) an mRNA comprising at least one coding sequence encoding a therapeutic protein, or a fragment or variant thereof, wherein the therapeutic protein is selected from the group consisting of (i) therapeutic proteins for use in enzyme replacement therapy for the treatment of metabolic, endocrine or amino acid disorders or for use in replacing a missing, deficient or mutated protein;(i) therapeutic proteins for use in the treatment of blood disorders, diseases of the circulatory system, diseases of the respiratory system, infectious diseases or immunodeficiencies; (iii) therapeutic proteins for use in the treatment of cancer or tumor diseases; (iv) therapeutic proteins for use in hormone replacement therapy; (v) therapeutic proteins for use in the reprogramming of somatic cells into omnipotent pluripotent stem cells; (vi) therapeutic proteins for use as an adjuvant or immunostimulation; (vii) therapeutic proteins that are a therapeutic antibody; (vii) therapeutic proteins that are a gene editing agent; and (ix) therapeutic proteins for use in the treatment or prevention of a liver disease selected from the group consisting of liver fibrosis, liver cirrhosis and liver cancer;wherein the antigen of item (a) encodes a pathogenic antigen selected from the group consisting of a bacterial, viral, fungal and protozoan antigen;wherein the pathogenic antigen is preferably derived from a SARS coronavirus 2 (SARS-CoV-2), nCoV-2019 coronavirus, SARS coronavirus (SARS-CoV), Bunyavirales virus, cytomegalovirus (CMV), dengue virus (DEN-1, DEN-2, DEN-3 and DEN-4), Ebola virus, Flavivirus, hepatitis B virus (HBV), herpes simplex virus (HSV), human immunodeficiency (HIV), human metapneumovirus (hMPV), human papillomavirus (HPV), human parainfluenza virus (HPIV), influenza virus, extraintestinal pathogenic E. coli, Lassa mammarenavirus (LASV), MERS coronavirus, Mycobacterium tuberculosis, Nipah virus, norovirus, rabies virus, respiratory syncytial virus (RSV), rhinovirus, rotavirus, vaccinia virus, fever virus yellow, Zika virus, Chlamydia trachomatis (i.e., the chlamydia bacterium that causes chlamydia) or malaria parasite (e.g., Plasmodium falciparum, Plasmodium vivax, Plasmodium malariae, or Plasmodium ovale).; 23. The composition according to any one of claims 14 to 22 for use (i) in the treatment or prophylaxis of infectious diseases; cancer or tumor diseases, disorders or conditions; liver diseases selected from the group consisting of liver fibrosis, liver cirrhosis and liver cancer; allergies; or autoimmune disease; disorder or condition; and / or (ii) for use in enzyme replacement therapy for the treatment of metabolic or endocrine disorders or for use in replacing a missing, deficient or mutated protein; the composition preferably comprises at least one coding RNA, wherein said at least one coding RNA comprises at least one coding sequence encoding at least one peptide or protein for use in the treatment or prevention of a disease, disorder or condition, wherein said composition is administered by intramuscular or intradermal injection to a subject in need thereof.

24. A kit or kit of parts, comprising any of the compositions of claims 18 to 23, optionally comprising a liquid carrier for solubilization and, optionally, technical instructions providing information on the administration and dosage of the components.

25. The composition according to any one of claims 18 to 22 or the kit or kit of parts according to claim 24 for use as a medicament.

26. A vaccine comprising a composition according to any one of claims 14 to 23 or a kit or kit of parts according to claim 24 for use in the prevention, prophylaxis, treatment and / or amelioration of a disease selected from infectious diseases including viral, bacterial or protozoological diseases, infectious diseases, cancer or tumor diseases.

27. A pharmaceutical composition comprising a composition according to any one of claims 14 to 23 or a kit or kit of parts of claim 24 for use in vaccinating a subject comprising an effective dose of mRNA encoding a viral antigen.