Nucleases in animal feed

Abstract

The present invention relates to a method for improving an animal's growth performance and / or its nutrient utilization by administering an animal feed composition comprising a feed additive or a feed supplement having at least one nuclease. The nucleases in the feed composition hydrolyze in-situ the nucleic acids (DNA / RNA) present along the gastrointestinal tract (GIT) of an animal which in turn improves the release of nutritive oligonucleotides in the GIT of an animal. The improved release of nutritive oligonucleotides improves an animal's growth performance and / or its nutrient utilization, especially during stages with high metabolism and / or fast growth of the animals.

Description

Nucleases in animal feed

[0001] FIELD OF THE INVENTION

[0002] The present invention relates to animal nutrition, particularly to methods for improving an animal growth performance and / or improving nutrient utilization and / or improving gut integrity and / or treatment or amelioration of subacute necrotic enteritis, comprising administering to an animal at least one nuclease, wherein the at least one nuclease is administered by means of a feed additive or feed supplement or by an animal feed composition comprising the feed additive or the feed supplement. The invention further relates to a feed additive or feed supplement or feed composition comprising at least one nuclease. Furthermore, the invention relates to a use of a feed additive or feed supplement or feed composition comprising at least one nuclease, for improving an animal growth performance, nutrient utilization, gut integrity, and / or resistance or treatment of necrotic enteritis.

[0003] BACKGROUND OF THE INVENTION

[0004] Feed additives and supplements for animal nutrition play a vital role in modem animal agriculture by optimizing nutrient utilization, promoting gut health, and enhancing overall animal performance. These additives offer several benefits, including improved feed efficiency, reduced disease susceptibility, enhanced animal welfare, and environmental sustainability through decreased waste production. They also contribute to increased production efficiency, address dietary deficiencies, and reduce the use of antibiotics, aligning with responsible agricultural practices.

[0005] The extensive use of antibiotics in livestock and animal nutrition has raised significant concerns in recent years. While antibiotics have traditionally been employed to promote growth and prevent disease in animals, the practice has come under scrutiny due to its potential negative implications. One major concern is the development of antibiotic-resistant bacteria, often referred to as "superbugs. " These resistant strains can pose a substantial threat to both animal and human health, as they can transfer antibiotic resistance genes to human pathogens through the food chain or direct contact. Additionally, the overuse of antibiotics in animal agriculture can lead to residues in meat and dairy products, which can have harmful effects on consumers. Furthermore, there is a growing awareness of the environmental impact of antibiotics in livestock farming, as they can enter water systems and affect ecosystems. As a result, there is a global shift towards more sustainable and responsible animal nutrition practices, including a focus on alternatives like probiotics, enzymes, and prebiotics to maintain animal health and well-being without relying on antibiotics.

[0006] For example, necrotic enteritis (NE) is a multifactorial disease with a cost to the poultry industry of over $2 billion annually. This disease is caused by bacteria, e.g., the anaerobic, gram-positive, and endospore-forming bacterium Clostridium perfringens and is typically managed using antibiotics. Indeed, NE and related diseases are an important reason for the use of various preventative / mitigatingstrategies, including the use of antibiotic growth promoters (AGP) in the production of poultry and other livestock. NE is known to cause damage to the gut of broilers showing large sections of necrotic intestinal tissue, the severity of which is associated with the strength of the disease. The clinical signs of NE include dehydration, orange colored frothy diarrhea and ruffled feathers. Furthermore, NE is associated with a decreased nutrient absorption and digestion, impaired feed conversion ratio (FOR) and reduced body weight gain (BWG).

[0007] The utilization of enzymes to enhance nutrient utilization, support gut health, modulate gut microbiota, and improve overall animal performance has gained significant attention in animal agriculture. Enzymes such as phytases, carbohydrases, and proteases have been employed as feed additives to break down complex feed components, making them more digestible for livestock. This enzymatic assistance leads to improved nutrient absorption, reduced feed wastage, and increased feed efficiency, resulting in enhanced animal growth and productivity. Moreover, certain enzymes, like xylanases, can positively influence gut health by breaking down indigestible components in the animal's diet, reducing the risk of digestive disorders.

[0008] This approach not only supports sustainable livestock production but also aligns with efforts to reduce the use of antibiotics in animal agriculture, making enzyme supplementation a valuable tool for optimizing animal performance and health.

[0009] For example, WO 2017 / 001703 relates to a method of improving the European Production Efficiency Factor (EPEF) and / or feed conversion ratio (FCR) of a monogastric animal, as well as a method of increasing the proportion of bacteria of genus Faecalibacterium in the microbiome of the gastrointestinal tract of a monogastric animal comprising administering to the animal an animal feed or animal feed additive comprising one or more microbial lysozymes.

[0010] WO 2019 / 121937 discloses an animal feed comprising an animal feed additive, one or more protein sources, one or more energy sources; the feed additive is composed by one or more polypeptides having muramidase activity, such as GH24 muramidase or GH25 muramidase having the ability of degrading cell wall debris from Lactobacillus johnsonii.

[0011] WO 2020 / 053275 relates to a method of treating, preventing or improving an infection, such as Eimeria and Clostridium perfringes infections, of a monogastric animal comprising administering to the animal a composition, an animal feed or an animal feed additive comprising one or more microbial muramidases.

[0012] Although effective in optimizing nutrient use, intestinal health and overall animal performance, the approaches presented so far are still costly.

[0013] Methods for applying nuclease enzymes as feed additives in either animals or humans, have not been explored with respect to their impact on growth performance and key health indicators, althoughthey might present a cost-effective solution, making them a viable option for enhancing animal and human health without incurring significant expense.

[0014] Nucleases are a class of enzymes with the ability to hydrolyze phosphodiester bonds in nucleic acid strands, which are the building blocks of genetic material in living organisms. Nucleic acids include DNA (deoxyribonucleic acid) and RNA (ribonucleic acid), and they carry and store genetic information. Nucleases play a crucial role in various biological processes by degrading these nucleic acids. They can be involved in DNA repair, replication, recombination, gene regulation, restriction digestion, RNA processing, RNA splicing, and proofreading during DNA replication, among other functions.

[0015] Nucleases can be classified into two main categories based on their mode of action: endonucleases, which cleave non-specific sequences within the interior of nucleic acid strands, and exonucleases, which cleave nucleotides from the ends of these strands. Nucleases can also be classified based on their substrate specificity for DNA, RNA, or both. Some nucleases are specific to DNA and are known as DNases, while others target RNA and are called RNases. Additionally, there are nucleases with broader substrate specificity that can cleave both DNA and RNA, referred to as nonspecific or endonucleases with mixed substrate specificity. This classification based on the type of nucleic acid they act upon further highlights the diversity and functional versatility of nucleases in cellular processes. A typical representative of DNases is DNase I from the pancreas of mammals. Typical representatives of RNases are, for example, RNase T1 and T2 from Aspergillus oryzae or RNase A also from the pancreas of mammals. A typical representative for DNA / RNA non-specific endonucleases is the endonuclease found in Serratia marcescens, which acts on double strand DNA, single strand DNA and RNA. Another example is the nuclease Pl from Penicillium citrinum, which cleaves both singlestranded DNA and RNA, with the latter being more preferred.

[0016] Nucleases are not only essential for normal cellular functions but are also valuable tools in molecular biology and biotechnology. Researchers often use nucleases to manipulate and modify nucleic acids in the laboratory for purposes such as gene editing, DNA sequencing, and creating recombinant DNA molecules.

[0017] Nuclease enzymes have been successfully produced and implemented in industrial settings primarily in the pharma (e.g., vaccine production / cell and gene therapy) and food fermentation end user markets. Within these end user markets the enzyme is typically used for the removal of recombinant DNA / RNA to ensure regulatory compliance in finished good products (e.g., food and / or feed enzyme solutions) or often to reduce viscosity in fermentation process where a high load of nucleic acids is observed.

[0018] However, there remains untapped potential for the utilization of nucleases in various other fields, such as animal nutrition. Thus, there remains a need for cost-effective solutions to improve efficiency of animal production process, making these processes more sustainable and economically viable.

[0019] It is an object of the invention to provide methods for improving an animal growth performance and / or improving nutrient utilization and / or improving gut integrity and / or treatment or amelioration of subacute necrotic enteritis, comprising administering to an animal at least one nuclease, wherein the at least one nuclease is administered by means of a feed additive or feed supplement or by an animal feed composition comprising the feed additive or the feed supplement. Such methods provide advantages over antibiotic interventions as typically used in systems for the livestock production, particularly for improving e.g., the animal growth performance under subacute necrotic enteritis. Specifically, the invention seeks to optimize growth performance and / or nutrient utilization, and / or gut integrity in animals facing subacute necrotic enteritis challenge, offering a more sustainable and effective alternative to antibiotic treatments. Moreover, by administering at least one nuclease in-situ to an animal, through a feed additive or feed supplement or by an animal feed composition comprising the feed additive or the feed supplement, the invention aims to provide methods that offer a cost-effective alternative compared, e.g., to the direct administration of nucleotides to the feed. Nucleotides are typically produced through additional industrial processes, e.g., from yeast extracts, which increases the costs of the feed. In contrast, the methods according to the invention aim to provide similar or improved benefits for the animals, while reducing production expenses, making them a more economical solution for livestock systems.

[0020] These objects have been achieved by the subject matter of the patent claims.

[0021] SUMMARY OF THE INVENTION

[0022] In summary, the present invention provides a method for improving an animal growth performance and / or improving nutrient utilization and / or improving gut integrity and / or treatment or amelioration of subacute necrotic enteritis, comprising administering to an animal at least one nuclease, wherein the at least one nuclease is administered by means of a feed additive or feed supplement or by an animal feed composition comprising the feed additive or the feed supplement.

[0023] The invention further relates to a method for improving an animal growth performance and / or nutrient utilization, comprising administering to an animal at least one nuclease, wherein the at least one nuclease is administered by means of a feed additive or feed supplement or by an animal feed composition comprising the feed additive or the feed supplement.

[0024] The invention further relates to a feed additive or feed supplement or feed composition comprising at least one nuclease.

[0025] The invention further relates to a use of a feed additive or feed supplement or feed composition comprising at least one nuclease, for improving an animal growth performance, nutrient utilization, gut integrity, and / or resistance or treatment of necrotic enteritis.

[0026] The invention further relates to a method for improving gut integrity and homeostasis, comprising administering to an animal at least one nuclease, wherein the at least one nuclease is administered by means of a feed additive or feed supplement and / or by an animal feed composition.

[0027] The invention further relates to a method for improving gut integrity, comprising administering to an animal at least one nuclease, wherein the at least one nuclease is administered by means of a feed additive or feed supplement or by an animal feed composition comprising the feed additive or the feed supplement.

[0028] The invention further relates to a method for treatment or amelioration of subacute necrotic enteritis, comprising administering to an animal at least one nuclease, wherein the at least one nuclease is administered by means of a feed additive or feed supplement or by an animal feed composition comprising the feed additive or the feed supplement.

[0029] The inventors have surprisingly found, that administering a feed additive or feed supplement comprising a nuclease according to the invention, or an animal feed composition also according to the invention comprising the feed additive or feed supplement of the invention, to an animal, leads to a series of benefits, measured under acute subclinical necrotic enteritis challenge, regarding the animal growth performance and / or nutrient utilization and / or gut integrity compared to the untreated control. This has been demonstrated by the inventors in the experimental section for example by measuring growth performance indicators such as the feed conversion ratio, body weight gain, mortality, necrotic enteritis lesion scores, oocyst per gram (OPG) count, gut integrity indicators such as villi length, crypt depth, villi width, and villus height to crypt depth ratio and nutrient utilization parameters such as nitrogen-corrected apparent metabolizable energy (AMEn), nutrient digestibility, such as dry matter (DM), energy and nitro gen / crude protein (CP). The testing of the animal feed composition of the invention comprising the feed additive or feed supplement also according to the invention was carried out under acute subclinical necrotic enteritis challenge in order to induce a controlled challenge to the animals to be able to assess the efficacy of the invention when compared against an non-treated control animals, antibiotic treated animals, and animals treated with oligonucleotide supplemented feed.

[0030] Without wishing to be bound by theory, the inventors believe that this is due to the fact that nucleic acids (DNA / RNA) present along the gastrointestinal tract (GIT) of an animal are hydrolyzed in-situ by the supplementary nuclease enzyme contained in the feed additive or feed supplement or animal feed composition of the invention, thus supporting and / or boosting the efficiency of normal cell proliferation, epithelial tissue regeneration in vivo, and concomitantly releasing and / or improving the release of nutritive oligonucleotides. Oligonucleotides are known to improve animal productivity with respect to average daily gain and FCR as well as boosting the immune system, reducing pathogenic infections and mortality. However, the synthesis of oligonucleotides or single nucleotides is a metabolically costly process and the in-situ hydrolyzation of nucleic acids may optimize cell proliferation to promote growth due to the improved release of nutritive oligonucleotides, especiallyduring stages with high metabolism and / or fast growth of the animals. Improvements in cell proliferation and epithelial tissue regeneration serve to support maintenance of gut integrity and functionality, as well as overall gut homeostasis, minimizing changes to microbial populations in the gut and gut function as well as improving the efficiency of interaction between microbiota and digested feed thus facilitating digestion and improving nutrient utilization (e.g. metabolizable energy) which may be gained from the feed.

[0031] Such benefits may be surprisingly observed after the administration of an animal feed comprising a feed additive or feed supplement comprising at least one nuclease, all according to the invention to either a monogastric or a ruminant animal. A particular benefit has been surprisingly observed in poultry. Currently, in practice in order to increase the level of oligonucleotides in the gastrointestinal tract (GIT) of an animal, the animal feed fed to an animal is supplemented with oligonucleotides. This method of increasing the level of oligonucleotides in the GIT of an animal has a number of drawbacks. Firstly, the external synthesis of oligonucleotides is a labor and energy intensive process and thus leads to additional process steps in order to produce an animal feed. Secondly, the cost of externally synthesized oligonucleotides is high and thus the cost of animal feed supplemented with oligonucleotides is also high. Therefore, the invention leads to an animal feed composition that is cheaper than existing oligonucleotide supplemented animal feed, and an animal feed that is less labor and energy intensive to produce.

[0032] DETAILED DESCRIPTION OF THE INVENTION

[0033] The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. As used herein, the term "and / or" includes any and all combinations of one or more of the associated listed items. As used herein, the singular forms “a”, “an”, and “the” are intended to include the plural forms as well as the singular forms, unless the context clearly indicates otherwise. It will be further understood that the terms “comprises” and / or “comprising”, when used in this specification, specify the presence of stated features, steps, operations, elements, and / or components, but do not preclude the presence or addition of one or more other features, steps, operations, elements, components, and / or groups thereof.

[0034] Unless otherwise defined, all terms (including technical and scientific terms) used herein have the same meaning as commonly understood by one having ordinary skill in the art to which this invention belongs. It will be further understood that terms, such as those defined in commonly used dictionaries, should be interpreted as having a meaning that is consistent with their meaning in the context of the relevant art and the present disclosure and will not be interpreted in an idealized or overly formal sense unless expressly so defined herein.

[0035] In describing the invention, it will be understood that a number of techniques and steps are disclosed. Each of these has individual benefit and each can also be used in conjunction with one ormore, or in some cases all, of the other disclosed techniques. Accordingly, for the sake of clarity, this description will refrain from repeating every possible combination of the individual steps in an unnecessary fashion. Nevertheless, the specification and claims should be read with the understanding that such combinations are entirely within the scope of the invention and the claims.

[0036] Novel methods comprising administering to an animal at least one nuclease, wherein the at least one nuclease is administered by means of a feed additive or feed supplement or by an animal feed composition comprising the feed additive or the feed supplement are described herein, as well as feed additives or feed compositions comprising at least one nuclease or uses thereof. In the following description, for purposes of explanation, numerous specific details are set forth in order to provide a thorough understanding of the present invention. It will be evident, however, to one skilled in the art that the present invention may be practiced without these specific details.

[0037] The present disclosure is to be considered as an exemplification of the invention and is not intended to limit the invention to the specific embodiments illustrated by description below.

[0038] The technical field of this invention is biotechnology and the exogenous supplementation of enzymes to animal feed (or animal nutrition). Enzymes are widely used in feed to improve nutrient utilization. Nucleases are a class of enzymes that play a crucial role in the breakdown and modification of nucleic acids, which include DNA and RNA. These enzymes are involved in various biological processes and have important applications in biotechnology and molecular biology. Nucleases have been successfully demonstrated to be useful in industrial settings in the pharma (e.g., vaccine production / cell & gene therapy) and food fermentation end user markets. However, the use of nucleases as an exogenous feed additive has never been considered as a system that could deliver health and animal growth performance benefits in vivo to either animals or humans.

[0039] A first aspect of the invention relates to a method for improving an animal growth performance and / or nutrient utilization, comprising administering to an animal at least one nuclease, wherein the at least one nuclease is administered by means of a feed additive or feed supplement or by an animal feed composition comprising the feed additive or the feed supplement.

[0040] A second aspect of the invention relates to a method for improving an animal growth performance, comprising administering to an animal at least one nuclease, wherein the at least one nuclease is administered by means of a feed additive or feed supplement or by an animal feed composition comprising the feed additive or the feed supplement.

[0041] A third aspect of the invention relates to a method for improving nutrient utilization in an animal, comprising administering to an animal at least one nuclease, wherein the at least one nuclease is administered by means of a feed additive or feed supplement or by an animal feed composition comprising the feed additive or the feed supplement.

[0042] A fourth aspect of the invention relates to a method for improving gut integrity and homeostasis of an animal, comprising administering to the animal at least one nuclease, wherein the at least one nuclease is administered by means of a feed additive or feed supplement and / or by an animal feed composition.

[0043] A fifth aspect of the invention relates to a method for improving gut integrity of an animal, comprising administering to the animal at least one nuclease, wherein the at least one nuclease is administered by means of a feed additive or feed supplement or by an animal feed composition comprising the feed additive or the feed supplement.

[0044] A sixth aspect of the invention relates to a method for treatment or amelioration of subacute necrotic enteritis in an animal, comprising administering to the animal at least one nuclease, wherein the at least one nuclease is administered by means of a feed additive or feed supplement or by an animal feed composition comprising the feed additive or the feed supplement.

[0045] In the context of the present disclosure, a “feed additive” is a substance or a mixture of substances that are added to animal feed to improve the nutritional value of the feed, enhance the growth and health of livestock, or achieve specific production goals; these additives are typically mixed with the animal's regular diet to provide essential nutrients, promote efficient digestion, prevent diseases, and improve overall feed quality. In the same way, a “feed supplement” is a substance or product added to an animal's regular diet to provide additional nutrients or other beneficial compounds that may be lacking or insufficient in the animal's basic feed. These supplements are designed to enhance the overall nutrition, health, growth, or performance of the animal. An animal feed additive or feed supplement of the present disclosure may be added to an animal feed composition.

[0046] For the purposes of the disclosure, the term “animal feed” refers to a specially formulated food product that is designed to provide essential nutrients and sustenance to domesticated animals. It serves as a primary source of nutrition for livestock, poultry, pets, and other animals raised in captivity. Animal feed is manufactured with the intention of meeting the specific dietary requirements of different species, ages, and production purposes, such as growth, reproduction, and / or maintenance. Animal feed typically includes a mixture of dietary ingredients, which can vary depending on the type of animal and its nutritional needs. Common components of animal feed, or dietary ingredients may include grains (like corn, wheat, and soybeans), oilseeds, forages, vitamins, minerals, and various additives. These ingredients are carefully balanced to ensure that animals receive the appropriate amounts of protein, carbohydrates, fats, vitamins, and minerals necessary for their overall health and productivity. Animal feed can be provided in various forms, such as pellets, grains, mixed rations, or even specially formulated feeds for specific animal types, like fish, poultry, or cattle. Animal diets can be manufactured as mash feed (non-pelleted) or pelleted feed (as whole pellets or crumbs). Typically, the milledfeedstuffs are mixed and sufficient amounts of essential vitamins and minerals are added according to the specifications for the species in question.

[0047] For the sake of clarification, the terms “ animal feed’, “feed additive" . and “feed supplement”, as employed herein, are related concepts in the context of providing nutrition to animals, but they serve different purposes and have distinct characteristics.

[0048] An “animal feed” is the primary source of nutrition for animals and is typically a complete diet that provides the basic nutrients necessary for their growth, maintenance, or reproduction. On the other hand, feed additives are substances added in small amounts to improve feed quality or animal performance, while feed supplements are specific additives used to address nutrient deficiencies or enhance specific aspects of an animal's health or production.

[0049] By the term "at least one, " it should be understood that the animal feed or feed supplement may include one or more nuclease enzymes. In other words, the feed or feed supplement can contain a single nuclease or a combination of multiple nuclease enzymes, depending on the desired characteristics and intended applications. Hence, the nuclease employed in this context can encompass a wide range of enzymes, or mixtures thereof. The number and types of nuclease enzymes employed can be determined based on factors such as the target animal species, nutritional requirements, and the desired effects on nucleic acid digestion and utilization within the digestive system.

[0050] For the purposes of the invention, a suitable “nuclease” is any enzyme having the ability to catalyze the hydrolysis of nucleic acid molecules, including DNA and RNA into smaller fragments. Examples of suitable nucleases include naturally occurring enzymes, recombinant enzymes and / or engineered enzymes or functional variants. These smaller DNA and RNA fragments typically consist of single nucleotides or short segments of nucleic acids, which can vary in length depending on the specific enzyme and reaction conditions employed. These fragments can range from one to a few nucleotide-bases up to longer stretches of nucleotides.

[0051] For the purposes of the invention, a naturally occurring enzyme, often referred to simply as a "natural enzyme" or “wild-type enzyme”, is an enzyme that is produced by living organisms, such as bacteria, plants, animals, or humans, without any genetic modification. These enzymes are part of the organism's biochemical machinery and serve various essential functions in biological processes.

[0052] For the purposes of the invention, an engineered enzyme, also known as functional variant or modified enzyme, is an enzyme that have been deliberately altered or modified through genetic engineering techniques to enhance or modify their properties, such as specificity, activity, stability, or substrate affinity compared to the reference (wild type) enzyme. These modifications are made to suit specific applications or industrial processes, where natural enzymes may not perform optimally or where new enzyme functions are desired.

[0053] Nucleases in the sense of the present invention are preferably all enzymes that are assigned to the EC classes of the International Union of Biochemistry and Molecular Biology described in Table 1, and their respective subclasses, or any functional fragment thereof or functional variant thereof.Table 1: EC classes of nuclease enzymes

[0054] For the purposes of the disclosure, the term "functional fragment" of an enzyme refers to fragments of the amino acid sequence of an enzyme comprising at least all the regions essential for exhibiting the biological or catalytic activity of said enzyme. This fragment is capable of performing a specific function that is characteristic for the full-length enzyme, such as substrate binding, catalysis, or interaction with other molecules. Functional fragments may lack some structural elements of the complete enzyme but still possess the essential regions required to exhibit a measurable level of the desired enzymatic activity.

[0055] For the purposes of the disclosure, the term "functional variant" refers to a modified form from the amino acid sequence of a protein or enzyme of reference (wild type) but that generally retains at least a portion of the reference protein or enzyme’s biological catalytic activity, preferably all the essential functional characteristics of said protein or enzyme of reference. The functional variant of the enzyme or protein may be structurally similar or structurally different Preferably, a “functional variant”,also referred herein as “nuclease variant” or “recombinant nuclease”, preferably covers a protein that is characterized by an amino acid sequence, which has an identity of at least 60%, preferably at least 70%, particular preferred at least 80%, most particularly preferred at least 90% to a reference (wild-type or native) nuclease, and which additionally exhibits nuclease activity.

[0056] In the sense of the invention, percent “ sequence identity” of a sequence is preferably calculated using BLASTP 2.2.20+ (Stephen F. Altschul, Thomas L. Madden, Alejandro A. Schaffer, Jinghui Zhang, Zheng Zhang, Webb Miller and David J. Lipman (1997), “Gapped BLAST and PSI-BLAST: a new generation of protein database search programs”, Nucleic Acids Res. 25:3389-3402; Stephen F. Altschul, John C. Wootton, E. Michael Gertz, Richa Agarwala, Aleksandr Morgulis, Alejandro A. Schaffer and Yi-Kuo Yu (2005).

[0057] For the purpose of the specification, the percent identity is calculated as: Sequence Identity [%] = number of Matches / L x 100, wherein L is the number of aligned positions, i.e. identities and nonidentities (including gaps, if any). Identity is preferably calculated using BLASTP (see, for example, Altschul SF et al. (1997) "Gapped BLAST and PSI-BLAST : a new generation of protein database search programs", Nucleic Acids Res. 25:3389-3402; or Altschul SF (2005) "Protein database searches using compositionally adjusted substitution matrices." FEBS J. 272:5101-5109); preferably with the following algorithm parameters: Matrix: BLOSUM62; Gap Costs: Existence: 11 Extension: 1, Expect threshold: 0.05, and Word size: 6. BlastP can be accessed online at the NCBI Homepage (https: / / blast.ncbi.nlm.nih.gov / Blast.cgi?PROGRAM=blastp&PAGE_TYPE=BlastSearch&LINK_LOC=blast home). Other program settings can be adjusted as desired, for example using the following settings:Field "Enter Query Sequence": Query subrange: none;Field "Choose Search Set": Database: non-redundant protein sequences (nr); optional parameters: noneField "Program Selection": Algorithm: blastp (protein-protein BLAST);Algorithm parameters: Field "General parameters": Max target sequences: 5000; Short queries: Automatically adjust parameters for short input sequences; Expect threshold: 0.05; Word size: 6; Max matches in a query range: 0;Algorithm parameters: Field "Scoring parameters": Matrix: BLOSUM62; Gap Costs: Ex-istence: 11 Extension: 1; Compositional adjustments: Conditional compositional score matrix adjustment;Algorithm parameters: Field "Filters and Masking": Filter: none; Mask: none.

[0058] In addition to the default parameters for calculation of percent identity, when aligning a reference sequence, referred to as "query sequence", with another sequence, referred to as "subject sequence", in particular wherein the query sequence is any of the sequences provided by the present invention; and wherein the subject sequence is any other sequence, for example a sequence disclosedin a database, the subject sequence must align over a sequence stretch covering at least 70% of the overall length of the query sequence ("sequence coverage" of at least 70%); the alignment of both sequences must cover at least 70% of the query sequence; for the purpose of specification, the sequence coverage is calculated as: the number of aligned positions, i.e. covering identities and non-identities (including gaps, if any) divided by the overall length of the query sequence and multiplied by 100. Alignments with a lower sequence coverage of the query sequence by the subject sequence are excluded for the determination of sequence identity for the purposes of this application. However, within the sequence coverage, the subject sequence may be longer or shorter than the length of the alignment.

[0059] In the sense of the invention “ nuclease activity" preferably means that the protein can catalyze the hydrolysis of nucleic acid molecules, such as DNA or RNA to form oligonucleotides or mononucleotides. This hydrolysis preferably occurs in aqueous solutions at an incubation temperature of -20° to 60° C resulting in the degradation of high-molecular, acid-insoluble DNA and / or RNA into low-molecular, acid-soluble oligo- and / or mononucleotides. The nuclease activity is preferably measured in a nuclease activity assay according to Example 1, which is based upon the release of mononucleotides or short, acid soluble oligonucleotides from a DNA substrate, e.g., calf thymus DNA, herring sperm DNA or salmon sperm DNA, which leads to an increase in absorbance at 260 nm. The nuclease activity assay can be further based upon the release of mononucleotides or short, acid soluble oligonucleotides from a RNA substrate, e.g. RNA from baker’s yeast. The nuclease activity is specified in Units. One Unit is preferably defined as the amount of enzyme (nuclease) that causes a change in absorbance at 260 nm of 1.0 Absorbance Unit in 30 minutes. Nucleases can cleave DNA or RNA or both. In this case “DNase” or “DNase activity” is understood to mean any DNA-degrading activity and “RNase” or “RNase activity” is understood to mean any RNA-degrading activity. DNA-degrading activity is measured in a nuclease activity assay using a DNA substrate and RNA-degrading activity is measured in a nuclease activity assay using a RNA substrate.

[0060] In preferred embodiments of the method according to the the invention, the at least one nuclease is selected from the group consisting of endonucleases, exonucleases, and mixed exo- / endonucleases.

[0061] In preferred embodiments of the method according to the invention, the at least one nuclease is selected from endonucleases.

[0062] For the purpose of the specification, “ endonucleases” are enzymes that catalyze the hydrolysis of phosphodiester bonds within a polynucleotide chain (namely DNA or RNA) at sequence-specific or non-specific internal locations, rather than at the ends of the molecule. Endonucleases are enzymes present across a broad spectrum of biological systems including procaryotic and eukaryotic organisms. Nucleases are known to be produced by the exocrine pancreas or the microbiota found within the digestive system of monogastric animals. Endonuclease activity in the gut is essential for the efficient digestion of nucleic acids, which can be further absorbed by the host gastrointestinal tract, contributingto the supply of purines, pyrimidines, and other metabolites that play essential roles in cellular functions and energy metabolism.

[0063] -In the context of the specification, “exonucleases” refer to nucleases that specifically act on the terminal ends of nucleic acid molecules, cleaving the phosphodiester bonds sequentially and releasing nucleotides. Exonucleases can be further categorized based on their direction of action, either cleaving nucleotides from the 5' end or the 3' end of the nucleic acid chain.

[0064] For the purpose of the specification, "mixed exo- / endonucleases" refer to nuclease enzymes that exhibit both exonuclease and endonuclease activities. This means they are capable of cleaving nucleotides from the terminal ends of a nucleic acid chain (like exonucleases) as well as cleaving internally within the nucleic acid strand (like endonucleases).

[0065] In preferred embodiments of the method according to the invention, the at least one nuclease has a DNA-degrading activity, an RNA-degrading activity, or a mixed DNA and RNA degrading activity.

[0066] In preferred embodiments of the method according to the invention, the at least one nuclease has a pure DNA-degrading activity.

[0067] In preferred embodiments of the method according to the invention, the at least one nuclease has a pure RNA-degrading activity.

[0068] In preferred embodiments of the method according to the invention, the at least one nuclease has a mixed DNA and RNA degrading activity.

[0069] In preferred embodiments of the method according to the invention, the at least one nuclease is selected from the group of enzymes classified under EC classes selected from EC3.1.11, EC3.1.13, EC3.1.14, EC3.1.21, EC3.1.25, EC 3.1.26, EC3.1.27, EC 3.1.30 and EC 3.1.31.

[0070] In preferred embodiments of the method according to the invention, the at least one nuclease is selected from the group of enzymes classified under EC classes selected from EC 3.1.26, EC 3.1.30 and EC 3.1.31.

[0071] In preferred embodiments of the method according to the invention, the at least one nuclease is selected from the group of enzymes classified under EC classes selected from EC 3.1.26 and EC 3.1.30.

[0072] In preferred embodiments of the method according to the invention, the at least one nuclease is selected from the group of enzymes classified under EC classes selected from EC 3.1.11.2, EC 3.1.11.5, EC 3.1.11.6, EC 3.1.13.4, EC 3.1.14.1, EC 3.1.21.1, EC 3.1.21.2, EC 3.1.21.3, EC 3.1.21.4,EC 3.1.21.6, EC 3.1.25.1, EC 3.1.26.3, EC 3.1.26.4, EC 3.1.26.5, EC 3.1.26.8, EC 3.1.26.9,EC 3.1.26.11, EC 3.1.27.1, EC 3.1.27.3, EC 3.1.27.5, EC 3.1.30.1, EC 3.1.30.2 and EC 3.1.31.1, any functional fragment or functional variant thereof.

[0073] In preferred embodiments of the method according to the invention, the at least one nuclease is selected from the group of enzymes classified under EC classes selected from EC 3.1.26.5 and EC 3.1.30.2.

[0074] In one embodiment, the nuclease is an endodeoxyribonuclease producing 5'- phosphomonoesters (EC class 3.1.21), a functional fragment or a functional variant thereof. Examples of suitable endodeoxyribonucleases producing 5 '-phosphomonoesters include, but are not limited to, deoxyribonuclease I (EC 3.1.21.1), deoxyribonuclease IV (EC 3.1.21.2), type I site-specific deoxyribonuclease (EC 3.1.21.3), type II site-specific deoxyribonuclease (EC 3.1.21.4), type III sitespecific deoxyribonuclease (EC 3.1.21.5), CC -preferring endodeoxyribo-nuclease (EC 3.1.21.6), deoxyribonuclease V (EC 3.1.21.7), T4 deoxyribonuclease II (EC 3.1.21.8), T4 deoxyribonuclease IV (EC 3.1.21.9), crossover junction endodeoxyribonuclease (EC 3.1.21.10), any functional fragment or variant thereof, and mixtures thereof.

[0075] In one embodiment, the nuclease is an endodeoxyribonuclease producing 3'- phosphomonoesters (EC class 3.1.22), a functional fragment or a functional variant thereof. Examples of suitable endodeoxyribonucleases producing 3 '-phosphomonoesters include, but are not limited to: deoxyribonuclease II (EC 3.1.22.1); Aspergillus deoxyribonuclease KI (EC 3.1.22.2); deoxyribonuclease V, which is now classified as EC 3.1.21.7 (formerly EC 3.1.22.3); crossover junction endodeoxyribonuclease, which is now classified as EC 3.1.21.10 (formerly EC 3.1.22.4); deoxyribonuclease X (EC 3.1.22.5); any functional fragment or variant thereof, and mixtures thereof.

[0076] In one embodiment, the nuclease is a site-specific endodeoxyribonuclease that are specific for altered bases (EC class 3.1.25), a functional fragment or a functional variant thereof. Examples of suitable site-specific endodeoxyribonucleases that are specific for altered bases include but are not limited to: deoxyribonuclease (pyrimidine dimer) (EC 3.1.25.1); en-dodeoxyribonuclease (apurinic or apyrimidinic), which is now classified as EC 4.2.99.18, DNA-(apurinic or apyrimidinic site) lyase (formerly EC 3.1.25.2); any functional fragment or variant thereof, and mixtures thereof.

[0077] In one embodiment, the nuclease is a site-specific endodeoxyribonuclease that is specific for altered bases (EC class 3.1.25), a functional fragment or a functional variant thereof. Examples of suitable site-specific endodeoxyribonucleases that are specific for altered bases include but are not limited to: deoxyribonuclease (pyrimidine dimer) (EC 3.1.25.1); endodeoxyribonuclease (apurinic or apyrimidinic), which is now classified as EC 4.2.99.18, DNA-(apurinic or apyrimidinic site) lyase (formerly EC 3.1.25.2); and mixtures thereof, any functional fragment or variant thereof, and mixtures thereof.

[0078] In one embodiment, the nuclease is an endoribonuclease producing 5'-phosphomonoesters (EC 3.1.26), a functional fragment or a functional variant thereof. Examples of suitable endoribonucleases producing 5'-phosphomonoesters include, but are not limited to: Physarumpolycephalum ribonuclease (EC 3.1.26.1); ribonuclease a (EC 3.1.26.2); ribonuclease III (EC 3.1.26.3); ribonuclease H (EC 3.1.26.4); ribonuclease P (EC 3.1.26.5); ribonuclease IV (EC 3.1.26.6); ribonuclease P4 (EC 3.1.26.7); ribonuclease M5 (EC 3.1.26.8); ribonuclease [poly-(U)-specific] (EC 3.1.26.9); ribonuclease IX (EC 3.1.26.10); tRNase Z (EC 3.1.26.11); ribonuclease E (EC 3.1.26.12); retroviral ribonuclease H (EC 3.1.26.13); any functional fragment or variant thereof, and mixtures thereof.

[0079] In one embodiment the nuclease is a Ribonuclease P (EC 3.1.26.5); any functional fragment or variant thereof, and mixtures thereof.

[0080] In one embodiment, the nuclease is an endoribonuclease producing 3'-phosphomonoesters (EC 3.1.27), a functional fragment or a functional variant thereof. Examples of suitable endoribonucleases producing 3'-phosphomonoesters include, but are not limited to: ribonuclease T2, which is now classified as EC 4.6.1.19 (formerly classified as EC 3.1.27.1); Bacillus subtilis ribonuclease, which is now classified as EC 4.6.1.22 (formerly classified as EC 3.1.27.2; ribonuclease Tl, which is now classified as EC 4.6.1.24 (formerly classified as EC 3.1.27.3); ribonuclease U2, which is now classified as EC 4.6.1.20 (formerly classified as EC 3.1.27.4); pancreatic ribonuclease (EC 4.6.1.18, formerly classified as EC 3.1.27.5); Enterobacter ribonuclease (EC 4.6.1.21, formerly classified as EC 3.1.27.6); ribonuclease F (EC 3.1.27.7); ribonuclease V (EC 3.1.27.8); tRNA-intron endonuclease (EC 4.6.1.16, formerly classified as EC 3.1.27.9); rRNA endonuclease (EC 4.6.1.23, formerly classified as EC 3. 1.27.10); any functional fragment or variant thereof, and mixtures thereof.

[0081] In one embodiment, the nuclease is an endoribonuclease that is active with either ribo- or deoxyribonucleic acids and produces 5 '-phosphomonoesters (EC 3.1.30), a functional fragment or a functional variant thereof. Examples of suitable endoribonucleases that are active with either ribo- or deoxyribonucleic acids and produce 5 '-phosphomonoesters include, but are not limited to: Aspergillus nuclease Si (EC 3.1.30.1); Serratia marcescens nuclease (EC 3.1.30.2); any functional fragment or variant thereof, and mixtures thereof.

[0082] In one embodiment the nuclease is an Aspergillus nuclease Si (EC 3.1.30.1); a Serratia marcescens nuclease (EC 3.1.30.2); any functional fragment or variant thereof, and mixtures thereof.

[0083] In one embodiment, the nuclease is an endoribonuclease that is active with either ribo- or deoxyribonucleic acids and produces 3 '-phosphomonoesters, a functional fragment or a functional variant thereof. Example of endoribonucleases that are active with either ribo- or deoxyribonucleic acids and produce 3 '-phosphomonoesters include, but are not limited to, micrococcal nuclease (EC 3.1.31.1), any functional fragment or variant thereof, and mixtures thereof.

[0084] In preferred embodiments of the method according to the invention, the at least one nuclease is derived from a microbial origin.

[0085] In one embodiment, the nuclease is of bacterial origin. Examples of suitable bacterial-derived nucleases include, but are not limited to endonucleases, exonucleases or mixed endo / exonucleases derived from gram-positive bacteria or gram-negative bacteria, any functional fragment or functional variant thereof. Preferably, the nuclease is a nuclease of a gram-negative bacterium.

[0086] In the sense of the present disclosure, the term “nuclease of a gram-negative bacterium" is preferably defined exclusively via the primary sequence of the mature nuclease or the DNA sequence of the corresponding wild-type bacterium encoding this primary sequence. If the expression in the Gram-positive bacterium should lead to post-translational modifications of the nuclease that do not occur in Gram-negative bacteria, or vice versa, then it is still a nuclease of a Gram-negative bacterium in the sense of the description.

[0087] The meaning of the term “gram-negative bacteria" in the sense of the present invention is the same as the meaning of the term in the prior art. Gram-negative bacteria, which preferably serve as a source for nucleases and are therefore preferred gram-negative bacteria in the sense of the present invention, are preferably all bacteria of the classes of proteobacteria such as alpha-proteobacteria, beta- proteobacteria, gamma-proteobacteria, delta-proteobacteria, epsilon-proteobacteria.

[0088] In preferred embodiments of the method according to the invention, the at least one nuclease is derived from a gram-negative bacterium, preferably selected from the group consisting of Acidithiobacillales, Aeromonadales, Alteromonadales, Cardiobacteriales, Chromatiales, Enterobacterales, Legionellales, Methylococcales, Oceanospirillales, Pasteurellales, Pseudomonadales, Thiotrichales, Vibrionales and Xanthomonadales, more preferably from Enterobacterales.

[0089] In preferred embodiments of the method according to the invention, the at least one nuclease is derived from a genus of the order Enterobacterales, selected from the group consisting of Arsenophonus, Brenneria, Buchnera, Budvicia, Buttiauxella, Cedecea, CAtrobacter, Dickeya, Edwardsiella, Enterobacter, Erwinia, Escherichia, Ewingella, Elafnia, Klebsiella, Kluyvera, Leclercia, Leminorella, Moellerella, Marganella, Obesumbacterium, Pantoea, Pectobacterium, Photorhabdus, Plesiomonas, Pragia, Proteus, Providencia, Rahnella, Raoultella, Saccharobacter, Salmonella, Samsonia, Serratia, Shigella, Sodalis, Tatumella, Thorsellia, Trabulsiella, Wigglesworthia, Xenorhabdus, Yersinia and Yokenella, preferably from Serratia.

[0090] In preferred embodiments of the method according to the the invention, the at least one nuclease is derived from a species of the genus Serratia selected from the group consisting of Serratia entomophila, Serratia ficaria, Serratia fonticola, Serratia grimesii, Serratia marcescens, Serratia liquefaciens, Serratia odorifera, Serratia plymuthica, Serratia proteamaculans, Serratia quinivorans, Serratia rubidaea and Serratia ureilytica.

[0091] In preferred embodiments of the method according to the invention, the at least one nuclease is derived from Serratia marcescens, any functional fragment or variant thereof, and mixtures thereof.

[0092] In preferred embodiments of the method according to the invention, the at least one nuclease is at least 70%, preferably at least 75%, more preferably at least 80%, even more preferably at least 85%, still more preferably at least 90%, still more preferably at least 95%, still more preferably at least 98%, most preferably at least 99%, or in particular at least 100% identical to the sequence of SEQ ID NO:1 or SEQ ID NO:2.

[0093] SEQ ID NO:1 is the amino acid sequence of the nuclease from Serratia marcescens. SEQ ID NO:2 is the amino acid sequence of the nuclease from Serratia marcescens with one additional methionine at its N-terminus:SEQ ID NO: 1:Asp Thr Leu Glu Ser l ie Asp Asn Cys Ala Vai Gly Cys Pro Thr Gly 1 5 10 15Gly Ser Ser Asn Vai Ser l ie Vai Arg His Ala Tyr Thr Leu Asn Asn20 25 30Asn Ser Thr Thr Lys Phe Ala Asn Trp Vai Ala Tyr His l ie Thr Lys35 40 45Asp Thr Pro Ala Ser Gly Lys Thr Arg Asn Trp Lys Thr Asp Pro Ala 50 55 60Leu Asn Pro Ala Asp Thr Leu Ala Pro Ala Asp Tyr Thr Gly Ala Asn65 70 75 80Ala Ala Leu Lys Vai Asp Arg Gly His Gin Ala Pro Leu Ala Ser Leu 85 90 95Ala Gly Vai Ser Asp Trp Glu Ser Leu Asn Tyr Leu Ser Asn l ie Thr100 105 110Pro Gin Lys Ser Asp Leu Asn Gin Gly Ala Trp Ala Arg Leu Glu Asp 115 120 125Gin Glu Arg Lys Leu l ie Asp Arg Ala Asp l ie Ser Ser Vai Tyr Thr130 135 140Vai Thr Gly Pro Leu Tyr Glu Arg Asp Met Gly Lys Leu Pro Gly Thr 145 150 155 160Gin Lys Ala His Thr l ie Pro Ser Ala Tyr Trp Lys Vai l ie Phe lie 165 170 175Asn Asn Ser Pro Ala Vai Asn His Tyr Ala Ala Phe Leu Phe Asp Gin180 185 190Asn Thr Pro Lys Gly Ala Asp Phe Cys Gin Phe Arg Vai Thr Vai Asp 195 200 205Glu lie Glu Lys Arg Thr Gly Leu l ie l ie Trp Ala Gly Leu Pro Asp210 215 220Asp Vai Gin Ala Ser Leu Lys Ser Lys Pro Gly Vai Leu Pro Glu Leu 225 230 235 240Met Gly Cys Lys Asn245SEQ ID NO: 2:Met Asp Thr Leu Glu Ser l ie Asp Asn Cys Ala Vai Gly Cys Pro Thr 1 5 10 15Gly Gly Ser Ser Asn Vai Ser l ie Vai Arg His Ala Tyr Thr Leu Asn20 25 30Asn Asn Ser Thr Thr Lys Phe Ala Asn Trp Vai Ala Tyr His He Thr35 40 45Lys Asp Thr Pro Ala Ser Gly Lys Thr Arg Asn Trp Lys Thr Asp Pro50 55 60Ala Leu Asn Pro Ala Asp Thr Leu Ala Pro Ala Asp Tyr Thr Gly Ala65 70 75 80Asn Ala Ala Leu Lys Vai Asp Arg Gly His Gin Ala Pro Leu Ala Ser85 90 95Leu Ala Gly Vai Ser Asp Trp Glu Ser Leu Asn Tyr Leu Ser Asn lie100 105 110Thr Pro Gin Lys Ser Asp Leu Asn Gin Gly Ala Trp Ala Arg Leu Glu115 120 125Asp Gin Glu Arg Lys Leu l ie Asp Arg Ala Asp l ie Ser Ser Vai Tyr130 135 140Thr Vai Thr Gly Pro Leu Tyr Glu Arg Asp Met Gly Lys Leu Pro Gly145 150 155 160Thr Gin Lys Ala His Thr l ie Pro Ser Ala Tyr Trp Lys Vai He Phe165 170 175 l ie Asn Asn Ser Pro Ala Vai Asn His Tyr Ala Ala Phe Leu Phe Asp180 185 190Gin Asn Thr Pro Lys Gly Ala Asp Phe Cys Gin Phe Arg Vai Thr Vai195 200 205Asp Glu lie Glu Lys Arg Thr Gly Leu l ie l ie Trp Ala Gly Leu Pro 210 215 220Asp Asp Vai Gin Ala Ser Leu Lys Ser Lys Pro Gly Vai Leu Pro Glu 225 230 235 240Leu Met Gly Cys Lys Asn245

[0094] In one embodiment, the nuclease is of fungal origin. Examples of suitable fungi-derived nucleases include, but are not limited to endonucleases, exonucleases, or mixed endo / exonucleases derived from various fungal species, each with its unique set of properties and advantages.

[0095] Particularly preferred are fungi of all orders of Ascomycota, Basidiomycota, Zygomycota, and Glomeromycota, among others, which serve as valuable sources of nucleases. These diverse fungal groups offer a wide array of nucleases with distinct properties, making them versatile for various biotechnological applications.

[0096] In other preferred embodiments of the method according to the invention, the at least one nuclease is derived from a fungus selected from the group consisting of Penicillium, Candida, Saccharomyces, and Trichoderma, preferably from Penicillium.

[0097] In preferred embodiments of the method according to the invention, the at least one nuclease is derived from Penicillium citrinum.

[0098] Penicillium citrinum-dcn cd nucleases are highly desirable due to their well-characterized properties and suitability for various molecular biology and biotechnological applications.

[0099] In one embodiment the nuclease is a Ribonuclease P from Penicillium citrinum, a functional fragment, or a functional variant thereof.

[0100] In preferred embodiments of the method according to the invention, the at least one nuclease is a recombinant protein.

[0101] For the purposes of the invention, a "recombinant protein" or a "recombinant enzyme” is an protein or enzyme produced through recombinant DNA technology, where the gene encoding the protein or enzyme is cloned and expressed in a host organism that does not naturally produce it. This process involves the insertion of genetic material into the expression host’s genome and / or into the expression host’s cell to direct the production of the desired protein or enzyme, often resulting in higher yields or enhanced properties, e.g., an enhanced purity compared to its naturally occurring counterpart.

[0102] For the purpose of the specification, when the at least one nuclease of the present invention is a recombinant protein (also referred to as recombinant nucleases), it may be prepared based on well- known methods in the art, including, but not limited to, site-specific mutagenesis, chimeragenesis, PCR, random mutagenesis, or recombination.

[0103] Standard procedures for cloning of genes and introducing mutations (random and / or site directed) may be used in order to obtain enzymes and enzyme variants such as the nuclease variants of the disclosure. For instance, techniques used to isolate or clone a polynucleotide are known in the art and include isolation from genomic DNA or cDNA, or a combination thereof. The cloning of thepolynucleotides from genomic DNA can be effected, e.g., by using polymerase chain reaction (PCR) or antibody screening of expression libraries to detect cloned DNA fragments with shared structural features. See, e.g., Innis et al., 1990, PCR: A Guide to Methods and Application, Academic Press, New York. Other nucleic acid amplification procedures such as ligase chain reaction (LCR), ligation activated transcription (LAT) and polynucleotide -based amplification (NASBA) may be used. Additional exemplary techniques are as described in Sambrook et al. (2012), Molecular cloning: A laboratory manual, Cold Spring Harbor lab., Cold Spring Harbor, N.Y.; Ausubel, F. M. et al. (eds.) “Current protocols in Molecular Biology”. John Wiley and Sons, 2003; Harwood, C. R., and Cutting, S. M. (eds.) “Molecular Biological Methods for Bacillus”. John Wiley and Sons, 1990.

[0104] Examples of recombinant nucleases include, but are not limited to, any functional variant of the above-described naturally occurring enzymes wherein, compared to the reference (wild type) amino acid sequence, comprising one or more amino acid substitutions, and / or one or more amino acid deletions, and / or one or more amino acid insertions or any combination thereof in at least one amino acid position.

[0105] In preferred embodiments of the method according to the invention, the at least one nuclease is a functional variant that retains nuclease activity of the reference nuclease.

[0106] In preferred embodiments of the method according to the invention, the functional variant of the nuclease exhibits an improved specific nuclease activity compared to the reference (wild type) nuclease, as measured under standard test conditions, preferably with the improvement being at least 5%, preferably at least 10%, more preferably at least 20%, even more preferably at least 100%.

[0107] For the purpose of the specification, “ specific activity” in this case is the catalytic activity (or nuclease activity) as measured under standard test conditions of a defined amount (weight) of protein of the nuclease. Particularly preferred are modifications, which preferably lead to more than 10%, more preferred more than 20%, further preferred more than 50% and most preferred more than 100% increase in the specific activity compared to the reference (wild-type) nuclease.

[0108] In preferred embodiments of the method according to the invention, the functional variant of the nuclease exhibits an improved thermal stability compared to the reference (wild type) nuclease, as measured under standard test conditions, preferably with the improvement being at least 5%, preferably at least 10%, more preferably at least 20%, even more preferably at least 100%.

[0109] For the purpose of the specification, the “thermal stability” of a nuclease is preferably characterized by a higher residual nuclease activity (nuclease activity as measured according to Example 1) after incubation for a specific time range e.g., 15, 30, 45 or 60 minutes, at a specific temperature, preferably at a temperature higher than the optimal temperature, compared to the residual activity of the reference (wild-type) nuclease. Preferably, residual activity is the ratio of activity determined for the nuclease at the elevated temperature and at optimal temperature expressed aspercentage. Particularly preferred are modifications, which preferably lead to an increase of residual activity of at least 10%, more preferably at least 20 %, still more preferably at least 30 %, yet more preferably at least 40 %, even more preferably at least 50 % and most preferably at least 60 % compared to the reference (wild-type) nuclease.

[0110] Examples of such thermally stable Serratia marcescens endonuclease variants are provided in WO2023 / 139240.

[0111] Preferably, the at least one nuclease contains amino acid substitutions T56P and / or E239A compared to the amino acid sequence of SEQ ID NO: 1.

[0112] In preferred embodiments of the method according to the invention, the at least one nuclease is at least 70%, preferably at least 75%, more preferably at least 80%, even more preferably at least 85%, still more preferably at least 90%, still more preferably at least 95%, still more preferably at least 98%, most preferably at least 99%, or in particular at least 100% identical to any one of the amino acid sequences SEQ ID NO:3, SEQ ID NO:4 or SEQ ID NO:5.

[0113] SEQ ID NO:3 is the amino acid sequence of the nuclease from Serratia marcescens (SEQ ID NO:1) in which an amino acid substitution is present at position 56, where threonine (T or Thr) is replaced with proline (P or Pro). This substitution is referred to as T56P.SEQ ID NO: 3:Asp Thr Leu Glu Ser l ie Asp Asn Cys Ala Vai Gly Cys Pro Thr Gly 1 5 10 15Gly Ser Ser Asn Vai Ser l ie Vai Arg His Ala Tyr Thr Leu Asn Asn20 25 30Asn Ser Thr Thr Lys Phe Ala Asn Trp Vai Ala Tyr His l ie Thr Lys 35 40 45Asp Thr Pro Ala Ser Gly Lys Pro Arg Asn Trp Lys Thr Asp Pro Ala 50 55 60Leu Asn Pro Ala Asp Thr Leu Ala Pro Ala Asp Tyr Thr Gly Ala Asn 65 70 75 80Ala Ala Leu Lys Vai Asp Arg Gly His Gin Ala Pro Leu Ala Ser Leu85 90 95Ala Gly Vai Ser Asp Trp Glu Ser Leu Asn Tyr Leu Ser Asn l ie Thr100 105 110Pro Gin Lys Ser Asp Leu Asn Gin Gly Ala Trp Ala Arg Leu Glu Asp115 120 125Gin Glu Arg Lys Leu l ie Asp Arg Ala Asp l ie Ser Ser Vai Tyr Thr130 135 140Vai Thr Gly Pro Leu Tyr Glu Arg Asp Met Gly Lys Leu Pro Gly Thr145 150 155 160Gin Lys Ala His Thr l ie Pro Ser Ala Tyr Trp Lys Vai l ie Phe lie165 170 175Asn Asn Ser Pro Ala Vai Asn His Tyr Ala Ala Phe Leu Phe Asp Gin 180 185 190Asn Thr Pro Lys Gly Ala Asp Phe Cys Gin Phe Arg Vai Thr Vai Asp 195 200 205Glu lie Glu Lys Arg Thr Gly Leu l ie l ie Trp Ala Gly Leu Pro Asp 210 215 220Asp Vai Gin Ala Ser Leu Lys Ser Lys Pro Gly Vai Leu Pro Glu Leu 225 230 235 240Met Gly Cys Lys Asn245

[0114] SEQ ID NO:4 is the amino acid sequence of the nuclease from Serratia marcescens (SEQ ID NO:1) in which an amino acid substitution is present at amino acid position 239, where glutamic acid (G or Glu) is replaced with alanine (A or Ala). This substitution is referred to as E239A.SEQ ID NO: 4:Asp Thr Leu Glu Ser l ie Asp Asn Cys Ala Vai Gly Cys Pro Thr Gly 1 5 10 15Gly Ser Ser Asn Vai Ser l ie Vai Arg His Ala Tyr Thr Leu Asn Asn20 25 30Asn Ser Thr Thr Lys Phe Ala Asn Trp Vai Ala Tyr His He Thr Lys 35 40 45Asp Thr Pro Ala Ser Gly Lys Thr Arg Asn Trp Lys Thr Asp Pro Ala 50 55 60Leu Asn Pro Ala Asp Thr Leu Ala Pro Ala Asp Tyr Thr Gly Ala Asn65 70 75 80Ala Ala Leu Lys Vai Asp Arg Gly His Gin Ala Pro Leu Ala Ser Leu85 90 95Ala Gly Vai Ser Asp Trp Glu Ser Leu Asn Tyr Leu Ser Asn He Thr 100 105 110Pro Gin Lys Ser Asp Leu Asn Gin Gly Ala Trp Ala Arg Leu Glu Asp 115 120 125Gin Glu Arg Lys Leu l ie Asp Arg Ala Asp l ie Ser Ser Vai Tyr Thr 130 135 140Vai Thr Gly Pro Leu Tyr Glu Arg Asp Met Gly Lys Leu Pro Gly Thr145 150 155 160Gin Lys Ala His Thr l ie Pro Ser Ala Tyr Trp Lys Vai l ie Phe lie165 170 175Asn Asn Ser Pro Ala Vai Asn His Tyr Ala Ala Phe Leu Phe Asp Gin180 185 190Asn Thr Pro Lys Gly Ala Asp Phe Cys Gin Phe Arg Vai Thr Vai Asp195 200 205Glu lie Glu Lys Arg Thr Gly Leu l ie l ie Trp Ala Gly Leu Pro Asp210 215 220Asp Vai Gin Ala Ser Leu Lys Ser Lys Pro Gly Vai Leu Pro Ala Leu225 230 235 240Met Gly Cys Lys Asn245

[0115] SEQ ID NO:5 is the amino acid sequence of the nuclease from Serratia marcescens (SEQ ID NO:1) in which two amino acid substitutions are present at amino acid positions 56 and 239, where threonine (T or Thr) is replaced with proline (P or Pro) at amino acid position 56 and where glutamic acid (G or Glu) is replaced with alanine (A or Ala) at amino acid position 239. These substitutions are referred to as T56P and E239A.SEQ ID NO: 5:Asp Thr Leu Glu Ser l ie Asp Asn Cys Ala Vai Gly Cys Pro Thr Gly 1 5 10 15Gly Ser Ser Asn Vai Ser He Vai Arg His Ala Tyr Thr Leu Asn Asn20 25 30Asn Ser Thr Thr Lys Phe Ala Asn Trp Vai Ala Tyr His He Thr Lys35 40 45Asp Thr Pro Ala Ser Gly Lys Pro Arg Asn Trp Lys Thr Asp Pro Ala 50 55 60Leu Asn Pro Ala Asp Thr Leu Ala Pro Ala Asp Tyr Thr Gly Ala Asn65 70 75 80Ala Ala Leu Lys Vai Asp Arg Gly His Gin Ala Pro Leu Ala Ser Leu 85 90 95Ala Gly Vai Ser Asp Trp Glu Ser Leu Asn Tyr Leu Ser Asn l ie Thr100 105 110Pro Gin Lys Ser Asp Leu Asn Gin Gly Ala Trp Ala Arg Leu Glu Asp115 120 125Gin Glu Arg Lys Leu l ie Asp Arg Ala Asp l ie Ser Ser Vai Tyr Thr130 135 140Vai Thr Gly Pro Leu Tyr Glu Arg Asp Met Gly Lys Leu Pro Gly Thr145 150 155 160Gin Lys Ala His Thr l ie Pro Ser Ala Tyr Trp Lys Vai l ie Phe lie165 170 175Asn Asn Ser Pro Ala Vai Asn His Tyr Ala Ala Phe Leu Phe Asp Gin180 185 190Asn Thr Pro Lys Gly Ala Asp Phe Cys Gin Phe Arg Vai Thr Vai Asp195 200 205Glu lie Glu Lys Arg Thr Gly Leu l ie l ie Trp Ala Gly Leu Pro Asp210 215 220Asp Vai Gin Ala Ser Leu Lys Ser Lys Pro Gly Vai Leu Pro Ala Leu225 230 235 240Met Gly Cys Lys Asn245

[0116] For the purpose of this specification, it is understood that when an amino acid sequence is provided, a skilled person will recognize that, to achieve expression of the amino acid sequence in a living organism, a methionine residue must be present at the N-terminus, either as the first amino acid or added at the beginning of the sequence. This applies e.g., for the amino acid sequences of SEQ ID NO:3, SEQ ID NO:4 and SEQ ID NO:5.

[0117] For the purpose of the specification “standard test conditions” refer to well-established specific experimental parameters and protocols under which the activity of the nuclease (or nuclease activity assay) is measured, ensuring consistency and reproducibility. These conditions typically include, but are not limited to, specific temperature ranges, humidity levels, pressure settings, and standardized testing protocols that ensure consistency and reliability of results. The techniques and conditions described herein are provided as illustrative examples. However, a skilled person in the field will appreciate how to modify and adapt these techniques and conditions based on specific requirements or varying circumstances.

[0118] In preferred embodiments of the present specification, the standard test conditions comprise assays for nuclease activity, preferably as described in Example 1. In other preferred embodiments of the specification, standard test conditions refer to the thermal stability. Routinely, thermal stability is characterized by a higher residual nuclease activity (as measured in Example 1) after incubation for a specific time range, e.g., from 15 to 60 minutes at a specific temperature, which is preferably higher than the optimal temperature of the reference (wild-type) nuclease. Such temperatures may be higherthan 23°C, preferably may range from 30°C to 90°C, more preferably from 40°C to 80°C, or still more preferably from 40°C to 70°C, even more preferably from 45°C to 55°C; even more preferably from 49°C to 53°C. Preferably, the residual activity is calculated as the ratio of absorbances measured for the sample at specific stability temperature (Tstabiiity) and at 23°C expressed as percentage (A260 [Tstabiiity] : A260 [T23°C])- In further embodiments of the specification, standard test conditions refer to the specific activity, which is the nuclease activity measured according to Example 1 of a defined amount (weight) of the protein (nuclease), e.g., the nuclease activity per milligram protein as given in Units per milligram. The amount of protein is preferably measured using a spectrophotometer at 280 nm. The protein concentration is calculated from absorbance using the molar extinction coefficient. Other possible methods to determine the protein amount include but are not limited to assays like Bradford or BCA.

[0119] The nuclease as defined by the present disclosure may be manufactured and obtained through various methods known in the art, including, but not limited to, isolation from organisms, such as bacteria, fungi, and plants; recombinant DNA technology; chemical synthesis; commercial sources; and purification from natural sources.

[0120] In preferred embodiments, the nuclease as described by the present disclosure is obtained through recombinant DNA technology. This involves inserting the gene that codes for the nuclease into a host organism, such as bacteria or yeast, and then using these modified organisms to produce the enzyme in large quantities via fermentative processes.

[0121] In preferred embodiments of the method according to the invention, the at least one nuclease is produced by a fermentation process using a bacterial host cell, preferably selected from Escherichia coli, Bacillus subtilis and Bacillus amyloliquefaciens, preferably containing a DNA sequence encoding the amino acid sequence of an endonuclease derived from Serratia marcescens.

[0122] In preferred embodiments, the nuclease as described by the present disclosure is obtained through isolation from organisms, such as bacteria or fungi. This typically involves a fermentation process to produce the enzymes on a larger scale. Preferably, the nuclease is produced through a fermentation process of a nuclease-naturally producing microorganism, such as a bacterium or a fungus.

[0123] In one particular embodiment, the nuclease is produced by a fermentation process of Penicillium citrinum.

[0124] In preferred embodiments of the method according to the invention, the at least one nuclease is administered at a dosage of at least about 100 U / kg of animal feed, preferably at least about 200 U / kg, more preferably at least about 400 U / kg, still more preferably at least about 800 U / kg, still more preferably at least about 1,200 U / kg, still more preferably at least about 1,500 U / kg, still more preferably at least about 2,000 U / kg of animal feed, still more preferably at least about 3,000 U / kg, still more preferably at least about 3,500 U / kg, still more preferably at least about 4,000 U / kg, still more preferably at least about 5,000 U / kg, still more preferably at least about 6,000 U / kg, still morepreferably at least about 7,000 U / kg, still more preferably at least about 8,000 U / kg, still more preferably at least about 9,000 U / kg, even more preferably at least about 10,000 U / kg, yet more preferably at least about 11,000 U / kg and most preferably at least about 12,000 U / kg, wherein the enzyme units are provided as DNase activity, wherein the dosage is provided through the feed additive, feed supplement, or animal feed composition comprising the feed additive or the feed supplement.

[0125] In preferred embodiments of the method according the invention, the at least one nuclease is administered at a dosage of at least about 1,000 U / kg of animal feed, preferably at least about 2,000 U / kg, more preferably at least about 5,000 U / kg, still more preferably at least about 6,000 U / kg, still more preferably at least about 7,000 U / kg, still more preferably at least about 8,000 U / kg, still more preferably at least about 9,000 U / kg, still more preferably at least about 10,000 U / kg, still more preferably at least about 11,000 U / kg, still more preferably at least about 12,000 U / kg, still more preferably at least about 13,000 U / kg, still more preferably at least about 14,000 U / kg, even more preferably at least about 15,000 U / kg, yet more preferably at least about 16,000 U / kg and most preferably at least about 16,600 U / kg, wherein the enzyme units are provided as RNase activity, wherein the dosage is provided through the feed additive, feed supplement, or animal feed composition comprising the feed additive or the feed supplement.

[0126] In preferred embodiments of the method according to the invention, the at least one nuclease is administered at a dosage ranging from about 100 to about 50,000 U / kg of animal feed, from about 200 to about 40,000 U / kg, more preferably about 300 to about 30,000 U / kg, still more preferably about 390 to about 20,000 U / kg, still more preferably about 390 to about 15,000 U / kg, even more preferably about 390 to about 14,000 U / kg, yet more preferably about 390 to about 12,000 U / kg, and particularly preferably at a final concentration ranging from about 390 to about 11,880 U / kg, wherein the enzyme units are provided as DNase activity, wherein the dosage is provided through the feed additive, feed supplement, or animal feed composition comprising the feed additive or the feed supplement.

[0127] In preferred embodiments of the method according to the invention, the at least one nuclease is administered at a dosage ranging from about 1,000 to about 50,000 U / kg of animal feed, from about 2,000 to about 40,000 U / kg, more preferably about 3,000 to about 30,000 U / kg, still more preferably about 4,000 to about 20,000 U / kg, still more preferably about 5,000 to about 18,000 U / kg and particularly preferably at a final concentration ranging from about 6,400 to about 16,687 U / kg, wherein the enzyme units are provided as RNase activity, wherein the dosage is provided through the feed additive, feed supplement, or animal feed composition comprising the feed additive or the feed supplement.

[0128] In preferred embodiments of the method according to the invention, a clinical or subclinical intestinal disease challenge is present in the animal.

[0129] Typically, the subacute necrotic enteritis is caused in an animal which has been or will be challenged with or exposed to Clostridium perfringens and / or Eimeria species. Such challenge or exposure may come from the environment or the application of live microorganisms in the feed or drinking water, e.g., upon experimental settings or when live attenuated coccidia vaccines are used.

[0130] In preferred embodiments of the method according to the invention, the clinical or subclinical intestinal disease challenge may be caused by a pathogenic microorganism.

[0131] Examples of pathogenic microorganisms include, but are not limited to, bacteria species, such as Salmonella, Campylobacter, Escherichia coli, Clostridium perfringens, Clostridium difficile, and Helicobacter spp; viruses, such as Avian Influenza Virus and Marek's Disease Virus; and parasites, such as Coccidia (Eimeria spp.) and its oocysts; Worms (e.g., Ascaridia, Heterakis, Capillaria), Tapeworms (e.g., Raillietina), and Giardia: Giardia.

[0132] In preferred embodiments of the method according to the invention, the clinical or subclinical intestinal disease challenge may be caused by a pathogenic bacterium.

[0133] In preferred embodiments of the method according to the invention, the pathogenic bacterium is Clostridium perfringens.

[0134] In preferred embodiments of the method according to the invention, the clinical or subclinical intestinal disease challenge includes additionally a challenge with Eimeria species.

[0135] In one embodiment, the presence of pathogenic microorganisms within the digestive system is measured in terms of the presence of Coccidia (Eimeria spp.) and its oocysts in the gastrointestinal tract.

[0136] In one embodiment, the presence of Coccidia (Eimeria spp.) and its oocysts is reduced in the gastrointestinal tract.

[0137] In preferred embodiments of the method according to the the invention, the feed additive or feed supplement or feed composition further comprises a suitable carrier.

[0138] For the purposes of the disclosure, a “ suitable carrier agent” refers to a substance or material that is safe for consumption by the target animals and does not pose any harm or adverse effects to their health. Feed additives and supplements are often used to improve the nutritional quality of animal feed or to deliver specific nutrients, vitamins, minerals, or other beneficial substances to enhance the health, growth, or production of livestock. Suitable carrier agents in this context serve as a vehicle or matrix for incorporating and delivering the active ingredients or supplements into the animal's diet. These carriers are chosen to ensure that they are compatible with the digestive system and metabolic processes of the specific animal species for which the feed additive or supplement is intended. The carriers must be safe, easily digestible, and not interfere with the absorption or utilization of the active components in the animal's body.

[0139] Examples of suitable carrier agents for animal feed additives or supplements may include various feed grains, proteins, fats, minerals, and other dietary components that are commonly part of the animal's diet. It's essential to ensure that these carriers do not have any negative impact on the health or performance of the animals consuming them. Compliance with relevant regulatory standards and guidelines is also crucial when formulating feed additives and supplements with suitable carrier agents.

[0140] For the purpose of the specification, the feed additive or feed supplement comprising the at least one nuclease as defined by the present disclosure may be added to an animal feed or animal feed composition in either a powder form or a liquid form. The feed additive may be powder that is added pre-pelleting, or a liquid that is applied (e.g., sprayed) post-pelleting.

[0141] For example, when in a powdered form, the feed additive or feed supplement is a low dust, dry blended and / or microgranulated enzyme powder combined with a suitable carrier agent, including but not limited to, rice bran, cereal, pseudocereal, wheat flour, maltodextrin, and / or calcium sulphate dihydrate (Gypsum — CaSO i). which is used to assist with mixing of the product in feed. Powdered enzyme systems are directly supplemented to animal feed before being fed to the animal in either mash or pelleted feed format. This product is made from a natural raw material and as such may be subject to some batch to batch color and / or odor variation, but these variations are not an indicator of enzyme activity and do not impact on product performance.

[0142] The nuclease in the present disclosure may be encapsulated to improve thermal protection. Examples of such encapsulation techniques include, but are not limited to, liposomal vesicles, hydrogel (such as polyethylene glycol) (PEG) hydrogel spheres, polymers (such as micellar polymer encapsulation like chitosan and Nafion), sol-gel, polyelectrolytes, and nanotubes of peptides and lipid.

[0143] In liquid form, the composition of the feed additive is a stabilized enzyme liquid derived from the natural fermentation medium of a nuclease-producing microorganism as described above (see fermentation process described herein). Enzyme stabilization is achieved by adding glycerol as a stabilizer and through the combination of glycerol as a stabilizer and preservatives such as calcium chloride and potassium sorbate which are added at the end of fermentation. Liquid enzyme systems are typically sprayed on to feed post pelleting using a post-pelleting liquid application system (PPLA) or can also be sprayed directly onto mash feed. This product is made from a natural raw material and as such may be subject to some batch-to-batch color and / or odor variation, but these variations are not an indicator of enzyme activity and do not impact on product performance.

[0144] In one embodiment, the animal feed composition comprises the feed additive or feed supplement of the present disclosure and at least one dietary ingredient.

[0145] Examples of dietary ingredients include, but are not limited to, grains and cereals, oilseeds and oilseed meals, forages and roughage, protein sources (including further enzymes), vitamins, minerals, fats and oils, carbohydrate sources, amino acids, and fiber sources.

[0146] Examples of grains and cereals include, but are not limited to, corn, wheat, barley, oats, sorghum, rice, rye, and combinations thereof.

[0147] Examples of oilseeds and oilseed meals include, but are not limited to, soybeans, soybean meal, sunflower seeds, sunflower meal, canola seeds, canola meal, cottonseed, cottonseed meal, and combinations thereof.

[0148] Examples of forages and roughage include, but are not limited to, hay, such as alfalfa, timothy, clover, silage, pasture grasses, straw, and combinations thereof.

[0149] Examples of protein sources include, but are not limited to, fish meal, meat and bone meal, poultry by-product meal, blood meal, feather meal, insect meal, pea protein, and combinations thereof.

[0150] Examples of vitamins include, but are not limited to, vitamin A, vitamin D, vitamin E, B- vitamins, such as Vitamin Bl, Vitamin B2, Vitamin B3, Vitamin B5, Vitamin B6, Vitamin B12, Vitamin K, Vitamin C, folic acid, and combinations thereof.

[0151] Examples of minerals include, but are not limited to, calcium, phosphorus, salt (sodium chloride), potassium, magnesium, iron, zinc, copper, selenium, manganese, and combinations thereof.

[0152] Examples of fats and oils include, but are not limited to, vegetable oils, animal oils, animal fats, and combinations thereof. Examples of vegetable oils include, but are not limited to, soybean oil, palm oil, com oil, sunflower oil, and combinations thereof. Examples of animal oils include, but are not limited to fish oil, cod liver oil, and combinations thereof. Examples of animal fats include, but are not limited to, tallow, lard, poultry fat, and combinations thereof.

[0153] Examples of carbohydrate sources include, but are not limited to, molasses, beet pulp, corn, wheat middling, rice bran, barley malt sprouts, oats, and combinations thereof.

[0154] Examples of amino acids include, but are not limited to, methionine, lysine, threonine, tryptophan, valine, isoleucine, leucine, arginine, histidine, phenylalanine, tyrosine, cysteine, glycine, serine, proline, alanine, aspartic acid, glutamic acid, and combinations thereof.

[0155] Examples of fiber sources include, but are not limited to, cellulose, alfalfa meal, wheat bran, oat hulls, soybean hulls, rice hulls, and combinations thereof.

[0156] The animal feed composition typically contains the following dietary ingredients: 0-80% maize, and / or 0-80% sorghum; and / or 0-70% wheat; and / or 0-70% barley; and / or 0-30% oats; and / or 0-40% soybean meal; and / or 0-25% fish meal; and / or 0-25% meat and bone meal; and / or 0-20% whey.

[0157] The feed additive or feed supplement comprising at least one nuclease of the present disclosure may be added to the animal feed composition (as solid or liquid), or to a given as a feed additive or premix.

[0158] In preferred embodiments of the method according to the invention, the feed additive or feed supplement or feed composition further comprises at least one feed additive, wherein the at least one further feed additive is an enzyme selected from the group of phytases, carbohydrases, and proteases.

[0159] Further additives may be added to the feed additive or feed supplement of the present disclosure or to the animal feed composition comprising the feed additive or feed supplement of the present disclosure.

[0160] In preferred embodiments of the method according to invention, the animal is a monogastric animal or a ruminant animal.

[0161] In one embodiment, the animal is a monogastric animal. In one preferred embodiment, the monogastric animal is selected from the group consisting of chicken, broiler, layer, pullet and chick, poultry, turkey, duck, quail, swine, piglet, growing pig, sow, guinea fowl, goose, pigeon, squab, horse, crustaceans, shrimps, prawns, fish, amberjack, arapaima, barb, bass, bluefish, bocachico, bream, bullhead, cachama, carp, catfish, catla, chanos, char, cichlid, cobia, cod, crappie, dorada, drum, eel, goby, goldfish, gourami, grouper, guapote, halibut, java, labeo, lai, loach, mackerel, milkfish, mojarra, mudfish, mullet, paco, pearlspot, pejerrey, perch, pike, pompano, roach, salmon, sampa, sauger, sea bass, seabream, shiner, sleeper, snakehead, snapper, snook, sole, spinefoot, sturgeon, sunfish, sweetfish, tench, terror, tilapia, trout, tuna, turbot, vendace, walleye and whitefish. In a preferred embodiment, the monogastric animal is a selected from the group consisting of chicken, broiler, layer, pullet, chick, poultry, turkey, duck, quail, swine, piglet, growing pig, sow, guinea fowl, goose, pigeon, and squab. In a more preferred embodiment, the monogastric animal is a selected from the group consisting of chicken, broiler, layer, chick, swine, piglet, growing pig, and sow.

[0162] In preferred embodiments of the method according to the invention, the monogastric animal is selected from the group consisting of birds, swine, dogs, cats, fish, shellfish, humans, primates, calves, and horses.

[0163] In one embodiment, the animal is a ruminant animal. In one preferred embodiment the ruminant animal is bovine, cattle, sheep, goats, camel, llama, alpaca, bison, deer, antelope, giraffes, yak, moose, caribou (reindeer), gazelles, pronghorn, gemsbok (oryx), kudu, waterbuck, hartebeest, sable antelope, wildebeest (gnu), and impala.

[0164] In preferred embodiments of the method according to the first aspect of the invention, the ruminant animal is selected from the group consisting of bovine, sheep, goat, camel, deer, llama, antelope, alpaca, and wildebeest.

[0165] In preferred embodiments of the method according to invention, the improved animal growth performance is measured in terms of at least one of the following parameters: improved feed conversion ratio (FCR), improved body weight adjusted feed conversion ratio (bwFCR), improved growth rate,improved body weight gain (BWG), improved European Production Efficiency Factor (EPEF), and / or reduced mortality.

[0166] In further preferred embodiments of the method according to the invention, the improved animal growth performance is measured in terms of at least one of the following parameters: improved feed conversion ratio (FCR), improved body weight adjusted feed conversion ratio (bwFCR), improved growth rate, improved body weight gain (BWG), improved European Production Efficiency Factor (EPEF), and / or reduced mortality and / or improved NE lesion score and / or reduced excretion of oocyst (OPG).

[0167] For the purpose of the specification, the parameters “feed conversion ratio" (FCR), “body weight adjusted feed conversion ratio" (bwFCR), “growth rate", “body weight gain" (BWG), “European Production Efficiency Factor" (EPEF), “mortality" , “NE lesion score" and / or “excretion of oocyst" (OPG) are widely recognized and commonly used in animal performance, health, and nutrition studies. A person skilled in the art is familiar with the methods for measuring these parameters and then- relevance to evaluating the effectiveness of feed additives, treatments, or management practices aimed at improving animal growth, efficiency, and health.

[0168] For the purpose of the specification, the term “feed conversion ratio" (FCR) is a measure of an animal's efficiency in converting feed mass into increased body mass. It is calculated as the ratio of the amount of feed intake to the amount of body weight gain over a specific period. An improved feed conversion ratio means a lower feed conversion ratio, signifying better feed utilization and growth performance. By “lower feed conversion ratio” or “improved feed conversion ratio” it is meant that the use of a feed additive composition in feed results in a lower amount of feed being required to be fed to an animal to increase the weight of the animal by a specified amount compared to the amount of feed required to increase the weight of the animal by the same amount when the feed does not comprise said feed additive or feed supplement or feed composition.

[0169] For the purpose of the specification, the term “body weight adjusted feed conversion ratio" (bwFCR) is a variation of the standard FCR, that accounts for differences in the animal’s body weight adjusting the FCR to more accurately reflect feed efficiency relative to the animal's size. This adjusted ratio provides a more standardized comparison across animals of varying weights, ensuring that the feed efficiency is not skewed by differences in growth stages or body size.

[0170] For the purpose of the specification, the term “growth rate" is the rate at which an animal gains body weight over a specific period, typically measured as the weight gained per day (e.g., grams per day or kilograms per day). Improved growth rate indicates that the animal is growing faster in response to better nutrient utilization, feed additives, and / or treatments compared to a baseline or control. This improvement typically reflects enhanced overall health, efficient feed conversion, and optimized metabolism, contributing to better productivity and performance.

[0171] For the purpose of the specification, the term “European Production Efficiency Factor” (EPEF) index used to evaluate the overall production performance of livestock, particularly poultry, by integrating multiple factors related to growth, feed efficiency, and survival. EPEF is calculated using the following formula: EPEF liveability (%) X 100

[0172] A higher EPEF indicates better overall efficiency in production, reflecting optimal growth, feed utilization, and animal health. It is a key parameter for assessing the success of nutritional programs, feed additives, and disease control strategies.

[0173] For the purpose of the specification, the terms “mortality rate" and "mortality" are defined as the percentage of animals that die during a specific period or production cycle, relative to the total number of animals at the start of the period. Mortality is the inverse of survival and is often used to assess the impact of disease, poor nutrition, or other adverse conditions. A reduced mortality or a reduced mortality rate indicate the effectiveness of interventions such as feed additives, treatments, or improved management practices in enhancing animal health and reducing death rates. It is typically measured as a percentage decrease in mortality relative to the control.

[0174] For the purpose of the specification, the term “NE lesion score" or “intestinal lesion score" refers to a quantitative or qualitative assessment of the severity and extent of intestinal lesions caused by necrotic enteritis in animals, particularly in poultry. The scoring system is used to evaluate the degree of damage to the intestinal lining, typically caused by Clostridium perfringens infection. Lesion scores are preferably graded on a numerical scale, with higher scores indicating more severe damage. The scoring is preferably based on a 0 to 3 score, with 0 being normal and 3 being the most severe. According to this specification, the scoring is to be understood as follows: 0 for normal intestines, 1 for slight mucus covering and loss of tone, 2 for severe necrotizing enteritis, and 3 for extreme necrotizing enteritis with presence of blood in the lumen. Therefore, an improved NE lesion score or an improved intestinal lesion score means a reduced NE lesion score value or a reduced intestinal lesion score value.

[0175] For the purpose of the specification, the term “excretion of oocyst” (OPG) refers to a quantitative measure of the number of oocysts, which are the infectious stages of parasitic protozoa (such as Eimeria species), excreted in the feces of an animal. This parameter is commonly used to assess the level of parasitic infection, particularly in the context of diseases like coccidiosis. Oocyst excretion per gram of feces is typically determined by collecting fecal samples and performing microscopic or molecular assays to count the number of oocysts present. The OPG count is a measure to monitor the risk of performance losses due to the load of coccidian parasites. A reduction in oocyst excretion per gram of feces is often used as an indicator of successful management of parasitic infections and / or improved animal health and / or improved growth performance.

[0176] In one embodiment according to any aspect of the invention, the FCR is improved by at least 1 %, preferably by at least 1.25%, more preferably by at least 1.5%, even more preferably by at least 1.75%, still more preferably by at least 2.0%, still more preferably by at least 3%, still more preferably by at least 4%, still more preferably by at least 5%, still more preferably by at least 6%, yet more preferably by at least 7% compared to the control.

[0177] In another embodiment according to any aspect of the invention, the FCR is improved by between 1% and 10%, such as between 2% and 10%, between 3% and 10%, 4% and 10%, 5% and 10%, between 6% and 10%, between 7% and 10%, between 8% and 10%, compared to the control, or any combination of these intervals.

[0178] In one embodiment according to any aspect of the invention, the bwFCR is improved by at least 1 %, preferably by at least 2%, more preferably by at least 3%, even more preferably by at least 4%, still more preferably by at least 6%, still more preferably by at least 7%, still more preferably by at least 8%, still more preferably by at least 9%, still more preferably by at least 10%, still more preferably by at least 11%, still more preferably by at least 12%, still more preferably by at least 13%, still more preferably by at least 14%, still more preferably by at least 15%, yet more preferably by at least 16%, compared to the control.

[0179] In another embodiment according to any aspect of the invention, the bwFCR is improved by between 1%, and 20%, such as between 2% and 19%, such as between 3% and 18%, such as between 4% and 17%, such as between 5% and 17%, such as between 6% and 17%, such as between 7% and 17%, such as between 8% and 17%, such as between 9% and 17%, or such as between 10% and 17% compared to the control, or any combination of these intervals.

[0180] In one embodiment according to any aspect of the invention, the growth rate is increased by at least 1 %, such as by at least 1.5%, at least 2.0%, at least 2.5%, at least 3%, at least 3.5%, at least 4%, at least 5%, at least 6%, or at least 7% compared to the control.

[0181] In another embodiment according to any aspect of the invention, the growth rate is improved by between 1 % and 15%, such as between 1 % and 12%, between 1 % and 10%, between 1.5% and 8%, or between 2.0% and 7% compared to the control, or any combination of these intervals.

[0182] In one embodiment according to any aspect of the invention, the EPEF is improved by at least 1 %, such as by at least 1.5%, at least 2.0%, at least 2.5%, at least 3%, at least 3.5%, at least 4%, at least 5%, at least 6%, at least 7%, at least 8%, at least 10%, at least 11%, at least 12%, at least 13%, at least 14%, at least 15% , at least 16%, at least 17%, at least 18%, at least 19%, at least 20%, at least 21% or at least 22% compared to the control.

[0183] In another embodiment according to any aspect of the invention, the EPEF is improved by between 1% and 25%, such as between 2% and 23%, such as between 3% and 22%, such as between4% and 22%, such as between 5% and 5%, such as between 6% and 22%, such as between 7% and 22%, such as between 8% and 22%, such as between 9% and 22%, such as between 10% and 22%, such as between 11% and 22%, such as between 12% and 22%, such as between 13% and 22%, such as between 14% and 22%, such as between 15% and 22%, such as between 16% and 22%, or between 17% and 22%, compared to the control, or any combination of these intervals.

[0184] In one embodiment according to any aspect of the invention, the mortality is reduced by at least by at least 75%, such as by at least 80%, at least 82%, at least 84%, at least 86%, at least 87%, or at least 88%, compared to the control.

[0185] In one embodiment according to any aspect of the invention, the mortality rate is not more than 10.0 %, not more than 9.0%; not more than 8.0%; not more than 7.0%; not more than 6.0%; not more than 5.0%; not more than 4.0%; not more than 3.0%; not more than 2.0%; not more than 1,8%, not more than 1,6%, not more than 1,4%, not more than 1,2%, not more than 1,1%, not more than 1,0%, not more than 0.8%, not more than 0.7%, or not more than 0.6%.

[0186] In another embodiment according to any aspect of the invention, the mortality rate is between not more than 10.0 % and 1.0 %, such as between 10 and 5 %; between 7.5 % and 2.5%; between 5.0% and 1.2%, between 1.39% and 0.62% or between 1.23% and 0.62%, or any combination of these intervals.

[0187] In one embodiment according to any aspect of the invention, the “NE lesion score” or “intestinal lesion score” is reduced by at least 30%, by at least 35%, by at least 40%, by at least 45%, by at least 50%, by at least 55%, by at least 60%, or by at least 65%, compared to the control.

[0188] In one embodiment according to any aspect of the invention, the OPG count is reduced by at least 5%, by at least 6%, by at least 8%, by at least 10%, by at least 15%, by at least 20%, by at least 22%, or by at least 25%, compared to the control.

[0189] For the purpose of this specification, "nutrient ut / 7 / zahon” or "nutrient digestibility" refers to the efficiency with which an animal's digestive system absorbs, metabolizes, and converts nutrients from feed into usable energy and biomass. Effective nutrient utilization or nutrient digestibility maximizes the absorption of essential nutrients — such as proteins, fats, carbohydrates, vitamins, and minerals — thereby supporting growth, maintenance, and overall health. Improvements in nutrient utilization or nutrient digestibility can lead to better feed efficiency, lower feed costs, and enhanced animal performance in livestock production systems.

[0190] In preferred embodiments of the method according to the invention, the improved nutrient utilization or nutrient digestibility is measured in terms of at least one of the following parameters: nutrient retention (NR), metabolizable energy digestibility, nitrogen-corrected apparent metabolizable energy (AMEn), and / or crude protein digestibility.

[0191] For the purpose of the specification, the parameters “nutrient retention” (NR) “nitrogen- corrected apparent metabolizable energy” (AMEn), “metabolizable energy digestibility” and “crude protein digestibility” are widely recognized and commonly used in animal performance, health, and nutrition studies. A person skilled in the art is familiar with the methods for measuring these parameters and their relevance to evaluating the effectiveness of feed additives, treatments, or management practices aimed at improving animal growth, efficiency, and health.

[0192] For the purpose of the specification, the term “nutrient retention” (NR) is a measure of the proportion of nutrients from feed that are absorbed and retained by the animal for growth, maintenance, and production, rather than being excreted in feces, urine, or gases. Nutrient retention provides an indication of the efficiency of nutrient utilization or digestibility by the animal, and it is commonly assessed for key nutrients such as metabolizable energy and nitrogen (N) or crude protein (CP). Nutrient retention is an important metric for assessing the effectiveness of feed additives, diets, or management practices in improving the overall efficiency of nutrient use, leading to better growth performance.

[0193] For the purpose of the specification, the term “nitrogen-corrected apparent metabolizable energy” (AMEn) is a measure of the energy available to an animal from feed, adjusted to account for nitrogen retention or losses, which reflects the energy that is actually metabolized and used for maintenance, growth, and production. AMEn is calculated by subtracting the energy lost in feces, urine, and gases from the gross energy of the feed, with a correction for the nitrogen content (which accounts for differences in protein metabolism). The nitrogen correction ensures that variations in protein intake and excretion do not bias the assessment of energy availability from non-protein sources. AMEn is a widely used parameter in animal nutrition studies to assess the true energy value of feed, ensuring that the energy contributions from protein are accurately represented. This measure helps optimize feed formulations and improve nutrient utilization efficiency.

[0194] For the purpose of the specification, “Metabolizable Energy Digestibility” refers to the amount of energy from feed that is available for metabolic processes after subtracting losses from feces, urine, and gases. It reflects how efficiently the animal converts the gross energy of the feed into usable energy for growth and maintenance.

[0195] For the purpose of the specification, “Crude Protein (CP) Digestibility” refers to the amount of CP (calculated from N, as CP=6.25xN) that is retained by the animal and used for tissue synthesis, growth, or maintenance after subtracting losses from feces, urine, and gases. CP digestibility is an indicator of protein utilization efficiency, with higher digestibility meaning more protein is being used productively by the animal rather than being lost as waste.

[0196] In one embodiment according to any aspect of the invention, the nutrient retention (NR) and / or nitrogen corrected apparent metabolizable energy (AMEn) and / or metabolizable energy digestibility and / or crude protein digestibility is increased by at least 1%; at least 1.5%, at least 2.0%, at least 2.5%,at least 3%, at least 3.5%, at least 4% or at least 5% compared to the control. In another embodiment, the nutrient retention (NR) for example metabolizable energy, nitrogen, is increased by between 1 % and 15%, such as between 1 % and 12%, between 1 % and 10%, 1.5% and 8%, 2.0% and 7% compared to the control, or any combination of these intervals.

[0197] In one embodiment according to any aspect of the invention, the improvement is compared to an animal feed or animal feed additive wherein the nuclease is not present (also referred herein to as the negative control).

[0198] For the purpose of the specification, the term “gut integrity and homeostasis" refers to the structural stability and balanced functioning of the gastrointestinal tract, which are essential for optimal nutrient absorption, immune defense, and disease resilience in livestock. Gut integrity denotes the strength and resilience of the epithelial barrier, which e.g., protects against the entry of pathogens, toxins, and undigested materials into the bloodstream, while gut homeostasis encompasses the harmonious interactions among the gut microbiota, immune responses, and epithelial cells, maintaining a stable and healthy digestive environment. Gut integrity and homeostasis support optimal nutrient absorption, immune regulation, and protection against infections, promoting overall health and growth in livestock.

[0199] In preferred embodiments of the method according to the invention, the improved gut integrity and homeostasis is measured in terms of at least one of the following parameters: villi height (VH), crypt depth (CD), villi width (VW), VH:CD ratio (VCR), villi surface area, intestinal lesion score, microbial density and / or presence of pathogenic or non-pathogenic microorganisms / organisms within the digestive system.

[0200] For the purpose of the specification “gut integrity” refers to the structural and functional stability of the gastrointestinal tract, characterized by a strong and cohesive epithelial barrier. This barrier consists of tightly connected epithelial cells that line the gut wall, preventing e.g., harmful pathogens from crossing into the bloodstream. Maintaining gut integrity is essential for nutrient absorption, immune regulation, and protection against infections. A stable gut integrity supports animal health by reducing inflammation, preventing leaky gut syndrome, and promoting efficient digestion, all of which are critical for optimal growth and productivity in livestock.

[0201] In preferred embodiments of the method according to the invention, the improved gut integrity is measured in terms of at least one of the following parameters: villi height (VH), crypt depth (CD), villi width (VW), VH:CD ratio (VCR), villi surface area, intestinal lesion score, microbial density and / or presence of pathogenic or non-pathogenic microorganisms / organisms within the digestive system.

[0202] The parameters “villi height” (VH), “crypt depth” (CD), “villi width” (VW), “VH. CD ratio” (VCR), “villi surface area” and “intestinal lesion score” are commonly used parameters in the evaluation of intestinal morphology, which are well-known to a person skilled in the art: They arepreferably used in studies assessing the impact of feed additives, treatments, or other interventions on gut morphology and function. These parameters are standard and well-established in the field of intestinal morphology and animal nutrition studies. A person skilled in the art is familiar with the methods for measuring these parameters and their relevance to assessing the health, absorptive function, and overall performance of the intestinal tract.

[0203] For the purpose of the specification, the term “villi height” (VH) refers to the vertical length of the villi, which are finger-like projections in the small intestine that increase the surface area for nutrient absorption. It is typically measured from the base to the tip of the villus. An increase in villi height is often associated with improved gut integrity, nutrient absorption and intestinal health, as it suggests a greater surface area for digestion and absorption of nutrients.

[0204] For the purpose of the specification, the term “crypt depth” (CD) refers to the vertical distance from the base of the intestinal crypts, which are invaginations at the base of the villi where new cells are produced, to the top of the crypt. Deeper crypts generally indicate higher rates of cell turnover and regeneration. However, excessive crypt depth can also indicate intestinal stress or damage. An optimal crypt depth is indicative of healthy intestinal tissue renewal. Preferably, the crypt depth should be decreased.

[0205] For the purpose of the specification, the term “villi width” (VW) refers to the horizontal width of the villi, measured at their base. A wider villus base may support increased structural stability and a larger surface area for nutrient absorption. Villi width, in combination with height, contributes to the overall surface area available for nutrient uptake.

[0206] For the purpose of the specification, the term “VH:CD ratio” (VCR), also known as Villi-to- Crypt Ratio, is a key indicator of gut integrity and intestinal health. It is calculated by dividing the villi height by the crypt depth. A higher VCR suggests a healthier intestine with longer villi and shallower crypts, which typically corresponds to better nutrient absorption and reduced intestinal inflammation. A lower ratio may indicate intestinal damage or stress, with shorter villi and deeper crypts reflecting poor absorption capacity.

[0207] For the purpose of the specification, the term “villi surface area” refers to the total surface area of the villi available for nutrient absorption in the small intestine. This is a critical factor for the effective digestion and absorption of nutrients, as a larger surface area increases the efficiency of these processes. Villi surface area is influenced by both villi height and width, with larger surface areas associated with improved gut health and / or nutrient utilization.

[0208] In one embodiment according to any aspect of the invention, the presence of pathogenic or non- pathogenic microorganisms / organisms / organisms within the digestive system is measured in terms of the presence of a pathogenic microorganism in the gastrointestinal tract.

[0209] Examples of pathogenic microorganisms / organisms to be monitored include, but are not limited to, bacteria species, such as Salmonella, Campylobacter, Escherichia coli, Clostridium perfringens, Clostridium difficile, and Helicobacter spp; viruses, such as Avian Influenza Virus and Marek's Disease Virus; and parasites, such as Coccidia (Eimeria spp.) and its oocysts; Worms (e.g., Ascaridia, Heterakis, Capillaria), Tapeworms (e.g., Raillietina), and Giardia: Giardia.

[0210] In one embodiment, the presence of pathogenic microorganisms / organisms within the digestive system is measured in terms of the presence of Coccidia (Eimeria spp.) and its oocysts in the gastrointestinal tract. In one embodiment, the presence of Coccidia (Eimeria spp.) and its oocysts is reduced in the gastrointestinal tract.

[0211] In one embodiment, the presence of pathogenic or non-pathogenic microorganisms / organisms / organisms within the digestive system is measured in terms of the microbial density of a non-pathogenic microorganism in the gastrointestinal tract.

[0212] Examples of non-pathogenic microorganisms include, but are not limited to, resident microbiome microorganisms, such as bacteria belonging to the genera / species Clostridium, Lactobacillus, Bacteroides, Escherichia coli, Ruminococcus, Faecalibacterium, Enterococcus, Streptococcus, Prevotella, Salmonella, Campylobacter, Helicobacter, Fusobacterium, Citrobacter, Enterobacter, Clostridium perfringens, Klebsiella, Proteus, Pseudomonas, and Bacillus; archaea belonging to the genera Methanobrevibacter and Methanosphaera; fungi belonging to the genera Candida, Saccharomyces, Aspergillus, and Penicillium.

[0213] In one embodiment according to any aspect of the invention, the villi height (VH) is increased by at least up to 1%; at least or up to 1.5%, at least or up to 2.0%, at least or up to 2.5%, at least or up to 3%, at least or up to 3.5%, at least or up to 4% or at least or up to 5% compared to the control. In another embodiment according to any aspect of the invention, the villi height (VH) is increased by at least or up to between 1 % and 15%, such as between 1 % and 12%, between 1 % and 10%, 1.5% and 8%, 2.0% and 7% compared to the control, or any combination of these intervals.

[0214] In one embodiment according to any aspect of the invention, the villi width (VW) is increased by at least up to 1%; at least or up to 1.5%, at least or up to 2.0%, at least or up to 2.5%, at least or up to 3%, at least or up to 3.5%, at least or up to 4% or at least or up to 5% compared to the control. In another embodiment according to any aspect of the invention, the villi height (VH) is increased by at least or up to between 1 % and 15%, such as between 1 % and 12%, between 1 % and 10%, 1.5% and 8%, 2.0% and 7% compared to the control, or any combination of these intervals.

[0215] In one embodiment according to any aspect of the invention, the crypt depth (CD) is decreased by at least or up to 1%; at least or up to 1.5%, at least or up to 2.0%, at least or up to 2.5%, at least or up to 3%, at least or up to 3.5%, at least or up to 4% or at least or up to 5% compared to the control. In another embodiment, the crypt depth (CD) is decreased by at least or up to between 1 % and 15%, suchas between 1 % and 12%, between 1 % and 10%, 1.5% and 8%, 2.0% and 7% compared to the control, or any combination of these intervals.

[0216] In one embodiment according to any aspect of the invention, the VH:CD ratio is increased by at least or up to 1%; at least or up to 1.5%, at least or up to 2.0%, at least or up to 2.5%, at least or up to 3%, at least or up to 3.5%, at least or up to 4% or at least or up to 5% compared to the control. In another embodiment, the VH:CD ratio is increased by at least or up to between 1 % and 15%, such as between 1 % and 12%, between 1 % and 10%, between 1 % and 8%, between 1 % and 6%, between 1 % and 4%, or between 1 % and 2%, compared to the control, or any combination of these intervals.

[0217] In one embodiment according to any aspect of the invention, the villi surface area is increased by at least or up to 1%; at least or up to 1.5%, at least or up to 2.0%, at least or up to 2.5%, at least or up to 3%, at least or up to 3.5%, at least or up to 4% or at least or up to 5% compared to the control. In another embodiment, the villi surface area is increased by at least or up to between 1 % and 15%, such as between 1 % and 12%, between 1 % and 10%, between 1 % and 8%, between 1 % and 6%, between 1 % and 4%, or between 1 % and 2%, compared to the control, or any combination of these intervals.

[0218] In preferred embodiments of the method according to the invention, the treatment or amelioration of subacute necrotic enteritis is measured in terms of at least one of the following parameters: improved feed conversion ratio (FCR), improved body weight adjusted feed conversion ratio (bwFCR), improved growth rate, improved body weight gain (BWG), improved European Production Efficiency Factor (EPEF), reduced mortality rate, improved nutrient retention (NR) such as metabolizable energy and / or nitrogen, reduced intestinal lesion score, improved villi height (VH), improved villi width (VW), improved crypt depth (CD), improved VH:CD ratio (VCR), improved villi surface area and / or presence of pathogenic microorganisms / organisms within the digestive system.

[0219] The terms "treatment" or “ amelioration" as used herein, refer to the reduction, prevention, or management of the severity, incidence, or progression of a disease or condition in an animal. These terms also include minimizing or controlling the negative effects of the disease on the animal's health, performance, or well-being, even if the disease is not entirely eliminated. In one embodiment, the subject may not be completely treated from subacute necrotic enteritis but may instead tolerate the condition, meaning the animal experiences reduced symptoms or milder effects without significant negative impact on its overall performance or productivity.

[0220] A seventh aspect of the invention relates to a feed additive or feed supplement comprising at least one nuclease.

[0221] In preferred embodiments of the seventh aspect of the invention, the at least one nuclease is selected from the group consisting of endonucleases, exonucleases, and mixed exo- / endonucleases.

[0222] In preferred embodiments of the seventh aspect if the invention, the at least one nuclease is selected from endonucleases.

[0223] In preferred embodiments of the seventh aspect of the invention, the at least one nuclease has a DNA-degrading activity, an RNA-degrading activity, or a mixed DNA and RNA degrading activity.

[0224] In preferred embodiments of the seventh aspect of the invention, the at least one nuclease has a pure DNA-degrading activity.

[0225] In preferred embodiments of the seventh aspect of the invention, the at least one nuclease has a pure RNA-degrading activity.

[0226] In preferred embodiments of the seventh aspect of the invention, the at least one nuclease has a mixed DNA and RNA degrading activity.

[0227] In preferred embodiments of the seventh aspect of the invention, the at least one nuclease is selected from the group of enzymes classified under EC classes selected from EC3.1.11, EC3.1.13, EC3.1.14, EC3.1.21, EC3.1.25, EC 3.1.26, EC3.1.27, EC 3.1.30 and EC 3.1.31.

[0228] In preferred embodiments of the feed additive or feed supplement according to the invention, the at least one nuclease is selected from the group of enzymes classified under EC classes selected from EC 3.1.26, EC 3.1.30 and EC 3.1.31.

[0229] In preferred embodiments of the method according to the invention, the at least one nuclease is selected from the group of enzymes classified under EC classes selected from EC 3.1.26 and EC 3.1.30.

[0230] In preferred embodiments of the seventh aspect of the invention, the at least one nuclease is selected from the group of enzymes classified under EC classes selected from EC 3.1.11.2, EC 3.1.11.5, EC 3.1.11.6, EC 3.1.13.4, EC 3.1.14.1, EC 3.1.21.1, EC 3.1.21.2, EC 3.1.21.3, EC 3.1.21.4,EC 3.1.21.6, EC 3.1.25.1, EC 3.1.26.3, EC 3.1.26.4, EC 3.1.26.5, EC 3.1.26.8, EC 3.1.26.9,EC 3.1.26.11, EC 3.1.27.1, EC 3.1.27.3, EC 3.1.27.5, EC 3.1.30.1, EC 3.1.30.2 and EC 3.1.31.1, any functional fragment or functional variant thereof.

[0231] In preferred embodiments of the seventh aspect of the invention, the at least one nuclease is selected from the group of enzymes classified under EC classes selected from EC 3.1.26.5 and EC 3.1.30.2.

[0232] In one embodiment, the nuclease is an endodeoxyribonuclease producing 5'- phosphomonoesters (EC class 3.1.21), a functional fragment or a functional variant thereof. Examples of suitable endodeoxyribonucleases producing 5 '-phosphomonoesters include, but are not limited to, deoxyribonuclease I (EC 3.1.21.1), deoxyribonuclease IV (EC 3.1.21.2), type I site-specific deoxyribonuclease (EC 3.1.21.3), type II site-specific deoxyribonuclease (EC 3.1.21.4), type III sitespecific deoxyribonuclease (EC 3.1.21.5), CC -preferring endodeoxyribo-nuclease (EC 3.1.21.6),deoxyribonuclease V (EC 3.1.21.7), T4 deoxyribonuclease II (EC 3.1.21.8), T4 deoxyribonuclease IV (EC 3.1.21.9), crossover junction endodeoxyribonuclease (EC 3.1.21.10), any functional fragment or variant thereof, and mixtures thereof.

[0233] In one embodiment, the nuclease is an endodeoxyribonuclease producing 3'- phosphomonoesters (EC class 3.1.22), a functional fragment or a functional variant thereof. Examples of suitable endodeoxyribonucleases producing 3 '-phosphomonoesters include, but are not limited to: deoxyribonuclease II (EC 3.1.22.1); Aspergillus deoxyribonuclease KI (EC 3.1.22.2); deoxyribonuclease V, which is now classified as EC 3.1.21.7 (formerly EC 3.1.22.3); crossover junction endodeoxyribonuclease, which is now classified as EC 3.1.21.10 (formerly EC 3.1.22.4); deoxyribonuclease X (EC 3.1.22.5); any functional fragment or variant thereof, and mixtures thereof.

[0234] In one embodiment, the nuclease is a site-specific endodeoxyribonuclease that are specific for altered bases (EC class 3.1.25), a functional fragment or a functional variant thereof. Examples of suitable site-specific endodeoxyribonucleases that are specific for altered bases include, but are not limited to: deoxyribonuclease (pyrimidine dimer) (EC 3.1.25.1); en-dodeoxyribonuclease (apurinic or apyrimidinic), which is now classified as EC 4.2.99.18, DNA-(apurinic or apyrimidinic site) lyase (formerly EC 3.1.25.2); any functional fragment or variant thereof, and mixtures thereof.

[0235] In one embodiment, the nuclease is a site-specific endodeoxyribonuclease that is specific for altered bases (EC class 3.1.25), a functional fragment or a functional variant thereof. Examples of suitable site-specific endodeoxyribonucleases that are specific for altered bases include, but are not limited to: deoxyribonuclease (pyrimidine dimer) (EC 3.1.25.1); endodeoxyribonuclease (apurinic or apyrimidinic), which is now classified as EC 4.2.99.18, DNA-(apurinic or apyrimidinic site) lyase (formerly EC 3.1.25.2); and mixtures thereof, any functional fragment or variant thereof, and mixtures thereof.

[0236] In one embodiment, the nuclease is an endoribonuclease producing 5'-phosphomonoesters (EC 3.1.26), a functional fragment or a functional variant thereof. Examples of suitable endoribonucleases producing 5'-phosphomonoesters include, but are not limited to: Physarum polycephalum ribonuclease (EC 3.1.26.1); ribonuclease a (EC 3.1.26.2); ribonuclease III (EC 3.1.26.3); ribonuclease H (EC 3.1.26.4); ribonuclease P (EC 3.1.26.5); ribonuclease IV (EC 3.1.26.6); ribonuclease P4 (EC 3.1.26.7); ribonuclease M5 (EC 3.1.26.8); ribonuclease [poly-(U)-specific] (EC 3.1.26.9); ribonuclease IX (EC 3.1.26.10); tRNase Z (EC 3.1.26.11); ribonuclease E (EC 3.1.26.12); retroviral ribonuclease H (EC 3.1.26.13); any functional fragment or variant thereof, and mixtures thereof.

[0237] In one embodiment the nuclease is a Ribonuclease P (EC 3.1.26.5); any functional fragment or variant thereof, and mixtures thereof.

[0238] In one embodiment, the nuclease is an endoribonuclease producing 3'-phosphomonoesters (EC 3.1.27), a functional fragment or a functional variant thereof. Examples of suitable endoribonucleases producing 3'-phosphomonoesters include, but are not limited to: ribonuclease T2, which is now classified as EC 4.6.1.19 (formerly classified as EC 3.1.27.1); Bacillus subtilis ribonuclease, which is now classified as EC 4.6.1.22 (formerly classified as EC 3.1.27.2; ribonuclease Tl, which is now classified as EC 4.6.1.24 (formerly classified as EC 3.1.27.3); ribonuclease U2, which is now classified as EC 4.6.1.20 (formerly classified as EC 3.1.27.4); pancreatic ribonuclease (EC 4.6.1.18, formerly classified as EC 3.1.27.5); Enterobacter ribonuclease (EC 4.6.1.21, formerly classified as EC 3.1.27.6); ribonuclease F (EC 3.1.27.7); ribonuclease V (EC 3.1.27.8); tRNA-intron endonuclease (EC 4.6.1.16, formerly classified as EC 3.1.27.9); rRNA endonuclease (EC 4.6.1.23, formerly classified as EC 3. 1.27.10); any functional fragment or variant thereof, and mixtures thereof.

[0239] In one embodiment, the nuclease is an endoribonuclease that is active with either ribo- or deoxyribonucleic acids and produces 5 '-phosphomonoesters (EC 3.1.30), a functional fragment or a functional variant thereof. Examples of suitable endoribonucleases that are active with either ribo- or deoxyribonucleic acids and produce 5 '-phosphomonoesters include, but are not limited to: Aspergillus nuclease Si (EC 3.1.30.1); Serratia marcescens nuclease (EC 3.1.30.2); any functional fragment or variant thereof, and mixtures thereof.

[0240] In one embodiment the nuclease is an Aspergillus nuclease Si (EC 3.1.30.1); a Serratia marcescens nuclease (EC 3.1.30.2); any functional fragment or variant thereof, and mixtures thereof.

[0241] In one embodiment, the nuclease is an endoribonuclease that is active with either ribo- or deoxyribonucleic acids and produces 3 '-phosphomonoesters, a functional fragment or a functional variant thereof. Example of endoribonucleases that are active with either ribo- or deoxyribonucleic acids and produce 3 '-phosphomonoesters include, but are not limited to, micrococcal nuclease (EC 3.1.31.1), any functional fragment or variant thereof, and mixtures thereof.

[0242] In preferred embodiments of the seventh aspect of the invention, the at least one nuclease is derived from a microbial origin.

[0243] In one embodiment, the nuclease is of bacterial origin. Examples of suitable bacterial-derived nucleases include, but are not limited to endonucleases, exonucleases or mixed endo / exonucleases derived from gram-positive bacteria or gram-negative bacteria, any functional fragment or functional variant thereof. Preferably, the nuclease is a nuclease of a gram-negative bacterium.

[0244] In preferred embodiments of the seventh aspect of the invention, the at least one nuclease is derived from a gram-negative bacterium, preferably selected from the group consisting of Acidithiobacillales, Aeromonadales, Alteromonadales, Cardiobacteriales, Chromatiales,Enterobacterales, Legionellales, Methylococcales, Oceanospirillales, Pasteurellales, Pseudomonadales, Thiotrichales, Vibrionales and Xanthomonadales, more preferably from Enterobacterales.

[0245] In preferred embodiments of the seventh aspect of the invention, the at least one nuclease is derived from a genus of the order Enterobacterales, selected from the group consisting of Arsenophonus, Brenneria, Buchnera, Budvicia, Buttiauxella, Cedecea, Citrobacter, Dickeya, Edwardsiella, Enterobacter, Erwinia, Escherichia, Ewingella, Elafnia, Klebsiella, Kluyvera, Leclercia, Leminorella, Moellerella, Marganella, Obesumbacterium, Pantoea, Pectobacterium, Photorhabdus, Plesiomonas, Pragia, Proteus, Providencia, Rahnella, Raoultella, Saccharobacter, Salmonella, Samsonia, Serratia, Shigella, Sodalis, Tatumella, Thorsellia, Trabulsiella, Wigglesworthia, Xenorhabdus, Yersinia and Yokenella, preferably from Serratia.

[0246] In preferred embodiments of the seventh aspect of the invention, the at least one nuclease is derived from a species of the genus Serratia selected from the group consisting of Serratia entomophila, Serratia ficaria, Serratia fonticola, Serratia grimesii, Serratia marcescens, Serratia liquefaciens, Serratia odorifera, Serratia plymuthica, Serratia proteamaculans, Serratia quinivorans, Serratia rubidaea and Serratia ureilytica.

[0247] In preferred embodiments of the seventh aspect of the invention, the at least one nuclease is derived from Serratia marcescens, any functional fragment or variant thereof, and mixtures thereof.

[0248] In preferred embodiments of the seventh aspect of the invention, the at least one nuclease is at least 70%, preferably at least 75%, more preferably at least 80%, even more preferably at least 85%, still more preferably at least 90%, still more preferably at least 95%, still more preferably at least 98%, most preferably at least 99%, or in particular at least 100% identical to the sequence of SEQ ID NO:1 or SEQ ID NO:2.

[0249] In one embodiment, the nuclease is of fungal origin. Examples of suitable fungi-derived nucleases include, but are not limited to endonucleases, exonucleases, or mixed endo / exonucleases derived from various fungal species, each with its unique set of properties and advantages.

[0250] Particularly preferred are fungi of all orders of Ascomycota, Basidiomycota, Zygomycota, and Glomeromycota, among others, which serve as valuable sources of nucleases. These diverse fungal groups offer a wide array of nucleases with distinct properties, making them versatile for various biotechnological applications.

[0251] In other preferred embodiments of the seventh aspect of the invention, the at least one nuclease is derived from a fungus selected from the group consisting of Penicillium, Candida, Saccharomyces, and Trichoderma, preferably from Penicillium.

[0252] In preferred embodiments of the seventh aspect of the invention, the at least one nuclease is derived from Penicillium citrinum.

[0253] In one embodiment the nuclease is a Ribonuclease P from Penicillium citrinum, a functional fragment, or a functional variant thereof.

[0254] In preferred embodiments of the seventh aspect of the invention, the at least one nuclease is a recombinant protein.

[0255] In preferred embodiments of the seventh aspect of the invention, the at least one nuclease is a functional variant that retains nuclease activity of the reference nuclease.

[0256] In preferred embodiments of the seventh aspect of the invention, the functional variant of the nuclease exhibits an improved specific nuclease activity compared to the reference (wild type) nuclease, as measured under standard test conditions, preferably with the improvement being at least 5%, preferably at least 10%, more preferably at least 20%, even more preferably at least 100%.

[0257] In preferred embodiments of the seventh aspect of the invention, the functional variant of the nuclease exhibits an improved thermal stability compared to the reference (wild type) nuclease, as measured under standard test conditions, preferably with the improvement being at least 5%, preferably at least 10%, more preferably at least 20%, even more preferably at least 100%.

[0258] In preferred embodiments of the seventh aspect of the invention, the at least one nuclease is produced by a fermentation process using a bacterial host cell, preferably selected from Escherichia coli, Bacillus subtilis and Bacillus amyloliquefaciens, preferably containing a DNA sequence encoding the amino acid sequence of an endonuclease derived from Serratia marcescens.

[0259] In one particular embodiment, the nuclease is produced by a fermentation process of Penicillium citrinum.

[0260] In preferred embodiments, the feed additive or feed supplement according to the seventh aspect of the invention, further comprises a suitable carrier.

[0261] In preferred embodiments, the feed additive or feed supplement according to the seventh aspect of the invention, further comprises at least one further feed additive, wherein the at least one further feed additive is an enzyme selected from the group of phytases, carbohydrases, and proteases.

[0262] In one embodiment, the further feed additive is at least one further enzyme, nucleotides, at least one yeast extract, and combinations thereof.

[0263] Examples of nucleotides include, but are not limited to, adenosine monophosphate (AMP), uridine monophosphate (UMP), guanosine monophosphate (GMP), cytidine monophosphate (CMP), a yeast extract, and combinations thereof.

[0264] In one embodiment, the further feed additive comprises at least one nucleotide source selected from the group consisting of adenosine monophosphate (AMP), uridine monophosphate (UMP),guanosine monophosphate (GMP), cytidine monophosphate (CMP), a yeast extract, and combinations thereof.

[0265] An eighth aspect of the invention relates to an animal feed composition comprising the feed additive or feed supplement according to any embodiment of the seventh aspect of the invention.

[0266] In preferred embodiments of the animal feed composition according to the invention, the at least one nuclease is added to the animal feed composition at a concentration of at least about 100 U / kg of animal feed, preferably at least about 200 U / kg, more preferably at least about 400 U / kg, still more preferably at least about 800 U / kg, still more preferably at least about 1,200 U / kg, still more preferably at least about 1,500 U / kg, still more preferably at least about 2,000 U / kg of animal feed, still more preferably at least about 3,000 U / kg, still more preferably at least about 3,500 U / kg, still more preferably at least about 4,000 U / kg, still more preferably at least about 5,000 U / kg, still more preferably at least about 6,000 U / kg, still more preferably at least about 7,000 U / kg, still more preferably at least about 8,000 U / kg, still more preferably at least about 9,000 U / kg, even more preferably at least about 10,000 U / kg, yet more preferably at least about 11,000 U / kg and most preferably at least about 12,000 U / kg, wherein the enzyme units are provided as DNase activity.

[0267] In preferred embodiments of the animal feed composition according to the invention, the at least one nuclease is added at a concentration ranging from about 100 to about 50,000 U / kg of animal feed, from about 200 to about 40,000 U / kg, more preferably about 300 to about 30,000 U / kg, still more preferably about 390 to about 20,000 U / kg, still more preferably about 390 to about 15,000 U / kg, even more preferably about 390 to about 14,000 U / kg, yet more preferably about 390 to about 12,000 U / kg, and particularly preferably at a final concentration ranging from about 390 to about 11,880 U / kg, wherein the enzyme units are provided as DNase activity.

[0268] In preferred embodiments of the animal feed composition according to the invention, the at least one nuclease is added at a concentration of at least about 1,000 U / kg of animal feed, preferably at least about 2,000 U / kg, more preferably at least about 5,000 U / kg, still more preferably at least about 6,000 U / kg, still more preferably at least about 7,000 U / kg, still more preferably at least about 8,000 U / kg, still more preferably at least about 9,000 U / kg, still more preferably at least about 10,000 U / kg, still more preferably at least about 11,000 U / kg, still more preferably at least about 12,000 U / kg, still more preferably at least about 13,000 U / kg, still more preferably at least about 14,000 U / kg, even more preferably at least about 15,000 U / kg, yet more preferably at least about 16,000 U / kg and most preferably at least about 16,600 U / kg, wherein the enzyme units are provided as RNase activity.

[0269] In preferred embodiments of the animal feed composition according to the invention, the at least one nuclease is added at a concentration ranging from about 1,000 to about 50,000 U / kg of animal feed, from about 2,000 to about 40,000 U / kg, more preferably about 3,000 to about 30,000 U / kg, still more preferably about 4,000 to about 20,000 U / kg, still more preferably about 5,000 to about 18,000U / kg and particularly preferably at a final concentration ranging from about 6,400 to about 16,687 U / kg, wherein the enzyme units are provided as RNase activity.

[0270] A ninth aspect of the invention relates to a use of a feed additive or feed supplement or feed composition according to any embodiments of the seventh aspect of the invention, for improving an animal growth performance, nutrient utilization, gut integrity, and / or resistance or treatment of necrotic enteritis.

[0271] In preferred embodiments of the use according the invention, the animal is a monogastric or a ruminant animal.

[0272] In preferred embodiments of the use according to the invention, the monogastric animal is selected from the group consisting of poultry, birds, swine, dogs, cats, fish, shellfish, humans, primates, calves, and horses.

[0273] In preferred embodiments of the use according to the invention, the ruminant animal is selected from the group consisting of bovine, sheep, goat, camel, deer, llama, antelope, alpaca, and wildebeest.

[0274] In preferred embodiments of the use according to the invention, the at least one nuclease is administered at a dosage of at least about 100 U / kg of animal feed, preferably at least about 200 U / kg, more preferably at least about 400 U / kg, still more preferably at least about 800 U / kg, still more preferably at least about 1,200 U / kg, still more preferably at least about 1,500 U / kg, still more preferably at least about 2,000 U / kg of animal feed, still more preferably at least about 3,000 U / kg, still more preferably at least about 3,500 U / kg, still more preferably at least about 4,000 U / kg, still more preferably at least about 5,000 U / kg, still more preferably at least about 6,000 U / kg, still more preferably at least about 7,000 U / kg, still more preferably at least about 8,000 U / kg, still more preferably at least about 9,000 U / kg, even more preferably at least about 10,000 U / kg, yet more preferably at least about 11,000 U / kg and most preferably at least about 12,000 U / kg, wherein the enzyme units are provided as DNase activity, wherein the dosage is provided through the feed additive, feed supplement, or animal feed composition comprising the feed additive or the feed supplement.

[0275] In preferred embodiments of the use according to the invention, the at least one nuclease is administered at a dosage ranging from about 100 to about 50,000 U / kg of animal feed, from about 200 to about 40,000 U / kg, more preferably about 300 to about 30,000 U / kg, still more preferably about 390 to about 20,000 U / kg, still more preferably about 390 to about 15,000 U / kg, even more preferably about 390 to about 14,000 U / kg, yet more preferably about 390 to about 12,000 U / kg, and particularly preferably at a final concentration ranging from about 390 to about 11,880 U / kg, wherein the enzyme units are provided as DNase activity, wherein the dosage is provided through the feed additive, feed supplement, or animal feed composition comprising the feed additive or the feed supplement.

[0276] In preferred embodiments of the use according to the invention, the at least one nuclease is administered at a dosage of at least about 1,000 U / kg of animal feed, preferably at least about 2,000 U / kg, more preferably at least about 5,000 U / kg, still more preferably at least about 6,000 U / kg, still more preferably at least about 7,000 U / kg, still more preferably at least about 8,000 U / kg, still more preferably at least about 9,000 U / kg, still more preferably at least about 10,000 U / kg, still more preferably at least about 11,000 U / kg, still more preferably at least about 12,000 U / kg, still more preferably at least about 13,000 U / kg, still more preferably at least about 14,000 U / kg, even more preferably at least about 15,000 U / kg, yet more preferably at least about 16,000 U / kg and most preferably at least about 16,600 U / kg, wherein the enzyme units are provided as RNase activity, wherein the dosage is provided through the feed additive, feed supplement, or animal feed composition comprising the feed additive or the feed supplement.

[0277] In preferred embodiments of the use according to the invention, the at least one nuclease is administered at a dosage ranging from about 1,000 to about 50,000 U / kg of animal feed, from about 2,000 to about 40,000 U / kg, more preferably about 3,000 to about 30,000 U / kg, still more preferably about 4,000 to about 20,000 U / kg, still more preferably about 5,000 to about 18,000 U / kg and particularly preferably at a final concentration ranging from about 6,400 to about 16,687 U / kg, wherein the enzyme units are provided as RNase activity, wherein the dosage is provided through the feed additive, feed supplement, or animal feed composition comprising the feed additive or the feed supplement.

[0278] In preferred embodiments of the use according to invention, the improved animal growth performance is measured in terms of at least one of the following parameters: improved feed conversion ratio (FCR), improved body weight adjusted feed conversion ratio (bwFCR), improved growth rate, improved body weight gain (BWG), improved European Production Efficiency Factor (EPEF), and / or reduced mortality.

[0279] In further preferred embodiments of the use according to the invention, the improved animal growth performance is measured in terms of at least one of the following parameters: improved feed conversion ratio (FCR), improved body weight adjusted feed conversion ratio (bwFCR), improved growth rate, improved body weight gain (BWG), improved European Production Efficiency Factor (EPEF), and / or reduced mortality and / or improved NE lesion score and / or reduced excretion of oocyst (OPG).

[0280] In one embodiment of the use according to the invention, the FCR is improved by at least 1 %, preferably by at least 1.25%, more preferably by at least 1.5%, even more preferably by at least 1.75%, still more preferably by at least 2.0%, still more preferably by at least 3%, still more preferably by at least 4%, still more preferably by at least 5%, still more preferably by at least 6%, yet more preferably by at least 7% compared to the control.

[0281] In another embodiment of the use according to the invention, the FCR is improved by between 1% and 10%, such as between 2% and 10%, between 3% and 10%, 4% and 10%, 5% and 10%, between 6% and 10%, between 7% and 10%, between 8% and 10%, compared to the control, or any combination of these intervals.

[0282] In one embodiment of the use according to the invention, the bwFCR is improved by at least 1 %, preferably by at least 2%, more preferably by at least 3%, even more preferably by at least 4%, still more preferably by at least 6%, still more preferably by at least 7%, still more preferably by at least 8%, still more preferably by at least 9%, still more preferably by at least 10%, still more preferably by at least 11%, still more preferably by at least 12%, still more preferably by at least 13%, still more preferably by at least 14%, still more preferably by at least 15%, yet more preferably by at least 16%, compared to the control.

[0283] In another embodiment of the use according to the invention, the bwFCR is improved by between 1%, and 20%, such as between 2% and 19%, such as between 3% and 18%, such as between 4% and 17%, such as between 5% and 17%, such as between 6% and 17%, such as between 7% and 17%, such as between 8% and 17%, such as between 9% and 17%, or such as between 10% and 17% compared to the control, or any combination of these intervals.

[0284] In one embodiment of the use according to the invention, the growth rate is increased by at least 1 %, such as by at least 1.5%, at least 2.0%, at least 2.5%, at least 3%, at least 3.5%, at least 4%, at least 5%, at least 6%, or at least 7% compared to the control.

[0285] In another embodiment of the use according to the invention, the growth rate is improved by between 1 % and 15%, such as between 1 % and 12%, between 1 % and 10%, between 1.5% and 8%, or between 2.0% and 7% compared to the control, or any combination of these intervals.

[0286] In one embodiment of the use according to the invention, the EPEF is improved by at least 1 %, such as by at least 1.5%, at least 2.0%, at least 2.5%, at least 3%, at least 3.5%, at least 4%, at least 5%, at least 6%, at least 7%, at least 8%, at least 10%, at least 11%, at least 12%, at least 13%, at least 14%, at least 15% , at least 16%, at least 17%, at least 18%, at least 19%, at least 20%, at least 21% or at least 22% compared to the control.

[0287] In another embodiment of the use according to the invention, the EPEF is improved by between 1% and 25%, such as between 2% and 23%, such as between 3% and 22%, such as between 4% and 22%, such as between 5% and 5%, such as between 6% and 22%, such as between 7% and 22%, such as between 8% and 22%, such as between 9% and 22%, such as between 10% and 22%, such as between 11% and 22%, such as between 12% and 22%, such as between 13% and 22%, such as between 14% and 22%, such as between 15% and 22%, such as between 16% and 22%, or between 17% and 22%, compared to the control, or any combination of these intervals.

[0288] In one embodiment of the use according to the invention, the mortality is reduced by at least by at least 75%, such as by at least 80%, at least 82%, at least 84%, at least 86%, at least 87%, or at least 88%, compared to the control.

[0289] In one embodiment of the use according to the invention, the mortality rate is not more than 10.0 %, not more than 9.0%; not more than 8.0%; not more than 7.0%; not more than 6.0%; not more than 5.0%; not more than 4.0%; not more than 3.0%; not more than 2.0%; not more than 1,8%, not more than 1,6%, not more than 1,4%, not more than 1,2%, not more than 1,1%, not more than 1,0%, not more than 0.8%, not more than 0.7%, or not more than 0.6%.

[0290] In another embodiment of the use according to the invention, the mortality rate is between not more than 10.0 % and 1.0 %, such as between 10 and 5 %; between 7.5 % and 2.5%; between 5.0% and 1.2%, between 1.39% and 0.62% or between 1.23% and 0.62%, or any combination of these intervals.

[0291] In one embodiment of the use according to the invention, the “NE lesion score” or “intestinal lesion score” is reduced by at least 30%, by at least 35%, by at least 40%, by at least 45%, by at least 50%, by at least 55%, by at least 60%, or by at least 65%, compared to the control.

[0292] In one embodiment of the use according to the invention, the OPG count is reduced by at least 5%, by at least 6%, by at least 8%, by at least 10%, by at least 15%, by at least 20%, by at least 22%, or by at least 25%, compared to the control.

[0293] In preferred embodiments of the use according to the invention, the improved nutrient utilization or nutrient digestibility is measured in terms of at least one of the following parameters: nutrient retention (NR), metabolizable energy digestibility, nitrogen-corrected apparent metabolizable energy (AMEn), and / or crude protein digestibility.

[0294] In one embodiment of the use according to the invention, the nutrient retention (NR) and / or nitrogen corrected apparent metabolizable energy (AMEn) and / or metabolizable energy digestibility and / or crude protein digestibility is increased by at least 1%; at least 1.5%, at least 2.0%, at least 2.5%, at least 3%, at least 3.5%, at least 4% or at least 5% compared to the control. In another embodiment, the nutrient retention (NR) for example metabolizable energy, nitrogen, is increased by between 1 % and 15%, such as between 1 % and 12%, between 1 % and 10%, 1.5% and 8%, 2.0% and 7% compared to the control, or any combination of these intervals. In one embodiment according to any aspect of the invention, the improvement is compared to an animal feed or animal feed additive wherein the nuclease is not present (also referred herein to as the negative control).

[0295] In preferred embodiments of the use according to the invention, the improved gut integrity is measured in terms of at least one of the following parameters: villi height (VH), crypt depth (CD), villi width (VW), VH:CD ratio (VCR), villi surface area, intestinal lesion score, microbial density and / or presence of pathogenic or non-pathogenic microorganisms / organisms within the digestive system.

[0296] In one embodiment of the use according to the invention, the presence of pathogenic or non- pathogenic microorganisms / organisms / organisms within the digestive system is measured in terms of the presence of a pathogenic microorganism in the gastrointestinal tract.

[0297] Examples of pathogenic microorganisms / organisms to be monitored include, but are not limited to, bacteria species, such as Salmonella, Campylobacter, Escherichia coli, Clostridium perfringens, Clostridium difficile, and Helicobacter spp; viruses, such as Avian Influenza Virus and Marek's Disease Virus; and parasites, such as Coccidia (Eimeria spp.) and its oocysts; Worms (e.g., Ascaridia, Heterakis, Capillaria), Tapeworms (e.g., Raillietina), and Giardia: Giardia.

[0298] In one embodiment, the presence of pathogenic microorganisms / organisms within the digestive system is measured in terms of the presence of Coccidia (Eimeria spp.) and its oocysts in the gastrointestinal tract. In one embodiment, the presence of Coccidia (Eimeria spp.) and its oocysts is reduced in the gastrointestinal tract.

[0299] In one embodiment, the presence of pathogenic or non-pathogenic microorganisms / organisms / organisms within the digestive system is measured in terms of the microbial density of a non-pathogenic microorganism in the gastrointestinal tract.

[0300] Examples of non-pathogenic microorganisms include, but are not limited to, resident microbiome microorganisms, such as bacteria belonging to the genera / species Clostridium, Lactobacillus, Bacteroides, Escherichia coli, Ruminococcus, Faecalibacterium, Enterococcus, Streptococcus, Prevotella, Salmonella, Campylobacter, Helicobacter, Fusobacterium, Citrobacter, Enterobacter, Clostridium perfringens, Klebsiella, Proteus, Pseudomonas, and Bacillus; archaea belonging to the genera Methanobrevibacter and Methanosphaera; fungi belonging to the genera Candida, Saccharomyces, Aspergillus, and Penicillium.

[0301] In one embodiment of the use according to the invention, the villi height (VH) is increased by at least up to 1%; at least or up to 1.5%, at least or up to 2.0%, at least or up to 2.5%, at least or up to 3%, at least or up to 3.5%, at least or up to 4% or at least or up to 5% compared to the control. In another embodiment according to any aspect of the invention, the villi height (VH) is increased by at least or up to between 1 % and 15%, such as between 1 % and 12%, between 1 % and 10%, 1.5% and 8%, 2.0% and 7% compared to the control, or any combination of these intervals.

[0302] In one embodiment of the use according to any aspect of the invention, the villi width (VW) is increased by at least up to 1%; at least or up to 1.5%, at least or up to 2.0%, at least or up to 2.5%, at least or up to 3%, at least or up to 3.5%, at least or up to 4% or at least or up to 5% compared to the control. In another embodiment according to any aspect of the invention, the villi height (VH) is increased by at least or up to between 1 % and 15%, such as between 1 % and 12%, between 1 % and 10%, 1.5% and 8%, 2.0% and 7% compared to the control, or any combination of these intervals.

[0303] In one embodiment of the use according to the invention, the crypt depth (CD) is decreased by at least or up to 1%; at least or up to 1.5%, at least or up to 2.0%, at least or up to 2.5%, at least or up to 3%, at least or up to 3.5%, at least or up to 4% or at least or up to 5% compared to the control. In another embodiment, the crypt depth (CD) is decreased by at least or up to between 1 % and 15%, such as between 1 % and 12%, between 1 % and 10%, 1.5% and 8%, 2.0% and 7% compared to the control, or any combination of these intervals.

[0304] In one embodiment of the use according to the invention, the VH:CD ratio is increased by at least or up to 1%; at least or up to 1.5%, at least or up to 2.0%, at least or up to 2.5%, at least or up to 3%, at least or up to 3.5%, at least or up to 4% or at least or up to 5% compared to the control. In another embodiment, the VH:CD ratio is increased by at least or up to between 1 % and 15%, such as between 1 % and 12%, between 1 % and 10%, between 1 % and 8%, between 1 % and 6%, between 1 % and 4%, or between 1 % and 2%, compared to the control, or any combination of these intervals.

[0305] In one embodiment of the use according to the invention, the villi surface area is increased by at least or up to 1%; at least or up to 1.5%, at least or up to 2.0%, at least or up to 2.5%, at least or up to 3%, at least or up to 3.5%, at least or up to 4% or at least or up to 5% compared to the control. In another embodiment, the villi surface area is increased by at least or up to between 1 % and 15%, such as between 1 % and 12%, between 1 % and 10%, between 1 % and 8%, between 1 % and 6%, between 1 % and 4%, or between 1 % and 2%, compared to the control, or any combination of these intervals.

[0306] In preferred embodiments of the use according to the invention, the treatment or amelioration of subacute necrotic enteritis is measured in terms of at least one of the following parameters: improved feed conversion ratio (FCR), improved body weight adjusted feed conversion ratio (bwFCR), improved growth rate, improved body weight gain (BWG), improved European Production Efficiency Factor (EPEF), reduced mortality rate, improved nutrient retention (NR) such as metabolizable energy and / or nitrogen, reduced intestinal lesion score, improved villi height (VH), improved villi width (VW), improved crypt depth (CD), improved VH:CD ratio (VCR), improved villi surface area and / or presence of pathogenic microorganisms / organisms within the digestive system.

[0307] Particularly preferred embodiments of the invention are compiled as clauses 1 to 205 hereinafter:Clause 1. A method for improving an animal growth performance and / or nutrient utilization, comprising administering to an animal at least one nuclease, wherein the at least one nuclease is administered by means of a feed additive or feed supplement or by an animal feed composition comprising the feed additive or the feed supplement.Clause 2. A method for improving an animal growth performance, comprising administering to an animal at least one nuclease, wherein the at least one nuclease is administered by means of a feed additive or feed supplement or by an animal feed composition comprising the feed additive or the feed supplement.Clause 3. A method for improving nutrient utilization in an animal, comprising administering to an animal at least one nuclease, wherein the at least one nuclease is administered by means of a feed additive or feed supplement or by an animal feed composition comprising the feed additive or the feed supplement.Clause 4. The method according to any of the preceding clauses, wherein the at least one nuclease is selected from the group consisting of endonucleases, exonucleases, and mixed exo- / endonucleases, preferably selected from endonucleases.Clause 5. The method according to any of the preceding clauses, wherein the at least one nuclease has a DNA-degrading activity, an RNA-degrading activity, or a mixed DNA and RNA degrading activity.Clause 6. The method according to any one of the preceding clauses, wherein the at least one nuclease is selected from the group of enzymes classified under EC classes selected from EC3.1.11, EC3.1.13, EC3.1.14, EC3.1.21, EC3.1.25, EC 3.1.26, EC3.1.27, EC 3.1.30 and EC 3.1.31.Clause 7. The method according to any one of the preceding clauses, wherein the at least one nuclease is selected from the group of enzymes classified under EC classes selected from EC 3.1.26, EC 3.1.30 and EC 3.1.31.Clause 8. The method according to any one of the preceding clauses, wherein the at least one nuclease is selected from the group of enzymes classified under EC classes selected from EC 3.1.26 and EC 3.1.30.Clause 9. The method according to clause 6, wherein the at least one nuclease is selected from the group of enzymes classified under EC classes selected from EC 3.1.11.2, EC 3.1.11.5, EC 3.1.11.6, EC 3.1.13.4, EC 3.1.14.1, EC 3.1.21.1, EC 3.1.21.2, EC 3.1.21.3, EC 3.1.21.4, EC 3.1.21.6, EC 3.1.25.1, EC 3.1.26.3, EC 3.1.26.4, EC 3.1.26.5, EC 3.1.26.8, EC 3.1.26.9, EC 3.1.26.11, EC 3.1.27.1, EC 3.1.27.3, EC 3.1.27.5, EC 3.1.30.1, EC 3.1.30.2 and EC 3.1.31.1.Clause 10. The method according to clause 9, wherein the at least one nuclease is selected from the group of enzymes classified under EC classes selected from EC 3.1.26.5 and EC 3.1.30.2.Clause 11. The method according to any of the preceding clauses, wherein the at least one nuclease is derived from a microbial origin.Clause 12. The method according to any of the preceding clauses, wherein the at least one nuclease is derived from a gram-negative bacterium, preferably selected from the group consisting of Acidithiobacillales, Aeromonadales, Alteromonadales, Cardiobacteriales, Chromatiales, Enterobacterales, Legionellales, Methylococcales, Oceanospirillales, Pasteurellales, Pseudomonadales, Thiotrichales, Vibrionales and Xanthomonadales, more preferably from Enterobacterales.Clause 13. The method according to any of the preceding clauses, wherein the at least one nuclease is derived from a genus of the order Enterobacterales, selected from the group consisting of Arsenophonus, Brenneria, Buchnera, Budvicia, Buttiauxella, Cedecea, Citrobacter, Dickeya, Edwardsiella,Enterobacter, Erwinia, Escherichia, Ewingella, Elafnia, Klebsiella, Kluyvera, Leclercia, Leminorella, Moellerella, Marganella, Obesumbacterium, Pantoea, Pectobacterium, Photorhabdus, Plesiomonas, Pragia, Proteus, Providencia, Rahnella, Raoultella, Saccharobacter, Salmonella, Samsonia, Serratia, Shigella, Sodalis, Tatumella, Thorsellia, Trabulsiella, Wigglesworthia, Xenorhabdus, Yersinia and Yokenella, preferably from Serratia.Clause 14. The method according to any of the preceding clauses, wherein the at least one nuclease is derived from a species of the genus Serratia selected from the group consisting of Serratia entomophila, Serratia ficaria, Serratia fonticola, Serratia grimesii, Serratia marcescens, Serratia liquefaciens, Serratia odorifera, Serratia plymuthica, Serratia proteamaculans, Serratia quinivorans, Serratia rubidaea and Serratia ureilytica,Clause 15. The method according to any of the preceding clauses, wherein the at least one nuclease is derived from Serratia marcescens.Clause 16. The method according to any of the preceding clauses, wherein the at least one nuclease is at least 70%, preferably at least 75%, more preferably at least 80%, even more preferably at least 85%, still more preferably at least 90%, still more preferably at least 95%, still more preferably at least 98%, most preferably at least 99%, or in particular at least 100% identical to the sequence of SEQ ID NO:1 or SEQ ID NO:2.Clause 17. The method according to any of clauses 1 to 11, wherein the at least one nuclease is derived from a fungus selected from the group consisting of Penicillium, Candida, Saccharomyces, and Trichoderma, preferably from Penicillium.Clause 18. The method according to clause 17, wherein the at least one nuclease is derived from Penicillium citrinum.Clause 19. The method according to any of the preceding clauses, wherein the at least one nuclease is a recombinant protein.Clause 20. The method according to any of the preceding clauses, wherein the at least one nuclease is a functional variant that retains nuclease activity of the reference nuclease.Clause 21. The method according to clause 20, wherein the functional variant of the nuclease exhibits an improved specific nuclease activity compared to the reference nuclease, as measured under standard test conditions, preferably with the improvement being at least 5%, preferably at least 10%, more preferably at least 20%, even more preferably at least 100%.Clause 22. The method according to any of clauses 20 and 21, wherein the functional variant of the nuclease exhibits an improved thermal stability compared to the reference nuclease, as measured under standard test conditions, preferably with the improvement being at least 5%, preferably at least 10%, more preferably at least 20%, even more preferably at least 100%.Clause 23. The method according to any of clauses 1 to 16 or 19 to 22, wherein the at least one nuclease is at least 70%, preferably at least 75%, more preferably at least 80%, even more preferably at least 85%, still more preferably at least 90%, still more preferably at least 95%, still more preferably at least 98%, most preferably at least 99%, or in particular at least 100% identical to any one of the amino acid sequences SEQ ID NO:3, SEQ ID NO:4 or SEQ ID NO:5.Clause 24. The method according to any of the preceding clauses, wherein the at least one nuclease is produced by a fermentation process using a bacterial host cell, preferably selected from Escherichia coli, Bacillus subtilis and Bacillus amyloliquefaciens .Clause 25. The method according to any of the preceding clauses, wherein the at least one nuclease is administered at a dosage of at least about 100 U / kg of animal feed, preferably at least about 200 U / kg, more preferably at least about 400 U / kg, still more preferably at least about 800 U / kg, still more preferably at least about 1,200 U / kg, still more preferably at least about 1,500 U / kg, still more preferably at least about 2,000 U / kg of animal feed, still more preferably at least about 3,000 U / kg, still more preferably at least about 3,500 U / kg, still more preferably at least about 4,000 U / kg, still more preferably at least about 5,000 U / kg, still more preferably at least about 6,000 U / kg, still more preferably at least about 7,000 U / kg, still more preferably at least about 8,000 U / kg, still more preferably at least about 9,000 U / kg, even more preferably at least about 10,000 U / kg, yet more preferably at least about 11,000 U / kg and most preferably at least about 12,000 U / kg, wherein the enzyme units are provided as DNase activity, wherein the dosage is provided through the feed additive, feed supplement, or animal feed composition comprising the feed additive or the feed supplement.Clause 26. The method according to clause 25, wherein the at least one nuclease is administered at a dosage ranging from about 100 to about 50,000 U / kg of animal feed, from about 200 to about 40,000 U / kg, more preferably about 300 to about 30,000 U / kg, still more preferably about 390 to about 20,000 U / kg, still more preferably about 390 to about 15,000 U / kg, even more preferably about 390 to about 14,000 U / kg, yet more preferably about 390 to about 12,000 U / kg, and particularly preferably at a final concentration ranging from about 390 to about 11,880 U / kg, wherein the enzyme units are provided as DNase activity, wherein the dosage is provided through the feed additive, feed supplement, or animal feed composition comprising the feed additive or the feed supplement.Clause 27. The method according to any of the preceding clauses, wherein the at least one nuclease is administered at a dosage of at least about 1,000 U / kg of animal feed, preferably at least about 2,000 U / kg, more preferably at least about 5,000 U / kg, still more preferably at least about 6,000 U / kg, still more preferably at least about 7,000 U / kg, still more preferably at least about 8,000 U / kg, still more preferably at least about 9,000 U / kg, still more preferably at least about 10,000 U / kg, still more preferably at least about 11,000 U / kg, still more preferably at least about 12,000 U / kg, still more preferably at least about 13,000 U / kg, still more preferably at least about 14,000 U / kg, even more preferably at least about 15,000 U / kg, yet more preferably at least about 16,000 U / kg and mostpreferably at least about 16,600 U / kg, wherein the enzyme units are provided as RNase activity, wherein the dosage is provided through the feed additive, feed supplement, or animal feed composition comprising the feed additive or the feed supplement.Clause 28. The method according to clause 27, wherein the at least one nuclease is administered at a dosage ranging from about 1,000 to about 50,000 U / kg of animal feed, from about 2,000 to about 40,000 U / kg, more preferably about 3,000 to about 30,000 U / kg, still more preferably about 4,000 to about 20,000 U / kg, still more preferably about 5,000 to about 18,000 U / kg and particularly preferably at a final concentration ranging from about 6,400 to about 16,687 U / kg, wherein the enzyme units are provided as RNase activity, wherein the dosage is provided through the feed additive, feed supplement, or animal feed composition comprising the feed additive or the feed supplement.Clause 29. The method according to any of the preceding clauses, wherein a clinical or subclinical intestinal disease challenge is present in the animal.Clause 30. The method according to clause 29, wherein the clinical or subclinical intestinal disease challenge may be caused by a pathogenic bacterium.Clause 31. The method according to any of clauses 29 and 30, wherein the pathogenic bacterium is Clostridium perfringens.Clause 32. The method according to any of clauses 29 to 31 , wherein the clinical or subclinical intestinal disease challenge includes additionally a challenge with Eimeria species.Clause 33. The method according to any of the preceding clauses, wherein the feed additive or feed supplement or feed composition further comprises a suitable carrier.Clause 34. The method according to any of the preceding clauses, wherein the feed additive or feed supplement or feed composition further comprises at least one feed additive, wherein the at least one further feed additive is an enzyme selected from the group of phytases, carbohydrases, and proteases.Clause 35. The method according to any of the preceding clauses, wherein the animal is a monogastric animal or a ruminant animal.Clause 36. The method according to clause 35, wherein the monogastric animal is selected from the group consisting of birds, swine, dogs, cats, fish, shellfish, humans, primates, calves, and horses.Clause 37. The method according to clause 35, wherein the ruminant animal is selected from the group consisting of bovine, sheep, goat, camel, deer, llama, antelope, alpaca, and wildebeest.Clause 38. The method according to any of the preceding clauses, wherein the improved animal growth performance is measured in terms of at least one of the following parameters: improved feed conversion ratio (FCR), improved body weight adjusted feed conversion ratio (bwFCR), improved growth rate, improved body weight gain (BWG), improved European Production Efficiency Factor (EPEF), and / or reduced mortality.Clause 39. The method according to any of the preceding clauses, wherein the improved nutrient utilization or nutrient digestibility is measured in terms of at least one of the following parameters: nutrient retention (NR), metabolizable energy digestibility, nitrogen-corrected apparent metabolizable energy (AMEn), and / or crude protein digestibility.Clause 40. A feed additive or feed supplement comprising at least one nuclease.Clause 41. The feed additive or feed supplement according to clause 40, wherein the at least one nuclease is selected from the group consisting of endonucleases, exonucleases, and mixed exo- / endonucleases, preferably selected from endonucleases.Clause 42. The feed additive or feed supplement according to clause 40 or 41, wherein the at least one nuclease has a DNA-degrading activity, an RNA-degrading activity, or a mixed DNA and RNA degrading activity.Clause 43. The feed additive or feed supplement according to any one of clauses 40 to 42, wherein the at least one nuclease is selected from the group of enzymes classified under EC classes selected from EC3.1.11, EC3.1.13, EC3.1.14, EC3.1.21, EC3.1.25, EC 3.1.26, EC3.1.27, EC 3.1.30 and EC 3.1.31.Clause 44. The feed additive or feed supplement according to any one of clauses 40 to 43, wherein the at least one nuclease is selected from the group of enzymes classified under EC classes selected from EC 3.1.26, EC 3.1.30 and EC 3.1.31.Clause 45. The feed additive or feed supplement according to any one of clauses 40 to 44, wherein the at least one nuclease is selected from the group of enzymes classified under EC classes selected from EC 3.1.26 and EC 3.1.30.Clause 46. The feed additive or feed supplement according to clause 43, wherein the at least one nuclease is selected from the group of enzymes classified under EC classes selected from EC 3.1.11.2, EC 3.1.11.5, EC 3.1.11.6, EC 3.1.13.4, EC 3.1.14.1, EC 3.1.21.1, EC 3.1.21.2, EC 3.1.21.3,EC 3.1.21.4, EC 3.1.21.6, EC 3.1.25.1, EC 3.1.26.3, EC 3.1.26.4, EC 3.1.26.5, EC 3.1.26.8,EC 3.1.26.9, EC 3.1.26.11, EC 3.1.27.1, EC 3.1.27.3, EC 3.1.27.5, EC 3.1.30.1, EC 3.1.30.2 and EC 3.1.31.1.Clause 47. The feed additive or feed supplement according to clause 46, wherein the at least one nuclease is selected from the group of enzymes classified under EC classes selected from EC 3.1.26.5 and EC 3.1.30.2.Clause 48. The feed additive or feed supplement according to any of clauses 40 to 47, wherein the at least one nuclease is derived from a microbial origin.Clause 49. The feed additive or feed supplement according to any of clauses 40 to 48, wherein the at least one nuclease is derived from a gram-negative bacterium, preferably selected from the group consisting of Acidithiobacillales, Aeromonadales, Alteromonadales, Cardiobacteriales, Chromatiales,Enterobacterales, Legionellales, Methylococcales, Oceanospirillales, Pasteurellales, Pseudomonadales, Thiotrichales, Vibrionales and Xanthomonadales, more preferably from Enterobacterales.Clause 50. The feed additive or feed supplement according to any of clauses 40 to 49, wherein the at least one nuclease is derived from a genus of the order Enterobacterales, selected from the group consisting of Arsenophonus, Brenneria, Buchnera, Budvicia, Buttiauxella, Cedecea, Citrobacter, Dickeya, Edwardsiella, Enterobacter, Erwinia, Escherichia, Ewingella, Elafnia, Klebsiella, Kluyvera, Leclercia, Leminorella, Moellerella, Marganella, Obesumbacterium, Pantoea, P ectobacterium, Photorhabdus, Plesiomonas, Pragia, Proteus, Providencia, Rahnella, Raoultella, Saccharobacter, Salmonella, Samsonia, Serratia, Shigella, Sodalis, Tatumella, Thorsellia, Trabulsiella, Wigglesworthia, Xenorhabdus, Yersinia and Yokenella, preferably from Serratia.Clause 51. The feed additive or feed supplement according to any of clauses 40 to 50, wherein the at least one nuclease is derived from a species of the genus Serratia selected from the group consisting of Serratia entomophila, Serratia ficaria, Serratia fonticola, Serratia grimesii, Serratia marcescens, Serratia liquefaciens, Serratia odorifera, Serratia plymuthica, Serratia proteamaculans, Serratia quinivorans, Serratia rubidaea and Serratia ureilytica,Clause 52. The feed additive or feed supplement according to any of clauses 40 to 51, wherein the at least one nuclease is derived from Serratia marcescens.Clause 53. The feed additive or feed supplement according to any of clauses 40 to 52, wherein the at least one nuclease is at least 70%, preferably at least 75%, more preferably at least 80%, even more preferably at least 85%, still more preferably at least 90%, still more preferably at least 95%, still more preferably at least 98%, most preferably at least 99%, or in particular at least 100% identical to the sequence of SEQ ID NO: 1 or SEQ ID NO:2.Clause 54. The feed additive or feed supplement according to any one of clauses 40 to 48, wherein the at least one nuclease is derived from a fungus selected from the group consisting of Penicillium, Candida, Saccharomyces, and Trichoderma, preferably from Penicillium.Clause 55. The feed additive or feed supplement according to clause 54, wherein the at least one nuclease is derived from Penicillium citrinum.Clause 56. The feed additive or feed supplement according to any of clauses 40 to 55, wherein the at least one nuclease is a recombinant protein.Clause 57. The feed additive or feed supplement according to any of clauses 40 to 56, wherein the at least one nuclease is a functional variant that retains nuclease activity of the reference nuclease.Clause 58. The feed additive or feed supplement according to clause 57, wherein the functional variant of the nuclease exhibits an improved specific nuclease activity compared to the reference nuclease, as measured under standard test conditions, preferably with the improvement being at least 5%, preferably at least 10%, more preferably at least 20%, even more preferably at least 100%.Clause 59. The feed additive or feed supplement according to any of clauses 57 and 58, wherein the functional variant of the nuclease exhibits an improved thermal stability compared to the reference nuclease, as measured under standard test conditions, preferably with the improvement being at least 5%, preferably at least 10%, more preferably at least 20%, even more preferably at least 100%.Clause 60. The method according to any of clauses 40 to 53 or 56 to 59, wherein the at least one nuclease is at least 70%, preferably at least 75%, more preferably at least 80%, even more preferably at least 85%, still more preferably at least 90%, still more preferably at least 95%, still more preferably at least 98%, most preferably at least 99%, or in particular at least 100% identical to any one of the amino acid sequences SEQ ID NO:3, SEQ ID NO:4 or SEQ ID NO:5.Clause 61. The feed additive or feed supplement according to any of clauses 40 to 60, wherein the at least one nuclease is produced by a fermentation process using a bacterial host cell, preferably selected from Escherichia coli, Bacillus subtilis and Bacillus amyloliquefaciens .Clause 62. The feed additive or feed supplement according to any of clauses 40 to 61, further comprising a suitable carrier.Clause 63. The feed additive or feed supplement according to any of clauses 40 to 62, further comprises at least one feed additive, wherein the at least one further feed additive is an enzyme selected from the group of phytases, carbohydrases, and proteases.Clause 64. An animal feed composition comprising the feed additive or feed supplement of any one of clauses 40 to 63.Clause 65. The animal feed composition according to clause 64, wherein the at least one nuclease is added to the animal feed composition at a concentration of at least about 100 U / kg of animal feed, preferably at least about 200 U / kg, more preferably at least about 400 U / kg, still more preferably at least about 800 U / kg, still more preferably at least about 1,200 U / kg, still more preferably at least about 1,500 U / kg, still more preferably at least about 2,000 U / kg of animal feed, still more preferably at least about 3,000 U / kg, still more preferably at least about 3,500 U / kg, still more preferably at least about 4,000 U / kg, still more preferably at least about 5,000 U / kg, still more preferably at least about 6,000 U / kg, still more preferably at least about 7,000 U / kg, still more preferably at least about 8,000 U / kg, still more preferably at least about 9,000 U / kg, even more preferably at least about 10,000 U / kg, yet more preferably at least about 11,000 U / kg and most preferably at least about 12,000 U / kg, wherein the enzyme units are provided as DNase activity.Clause 66. The animal feed composition according to clause 65, wherein the at least one nuclease is added at a concentration ranging from about 100 to about 50,000 U / kg of animal feed, from about 200 to about 40,000 U / kg, more preferably about 300 to about 30,000 U / kg, still more preferably about 390 to about 20,000 U / kg, still more preferably about 390 to about 15,000 U / kg, even more preferably about 390 to about 14,000 U / kg, yet more preferably about 390 to about 12,000 U / kg, and particularlypreferably at a final concentration ranging from about 390 to about 11,880 U / kg, wherein the enzyme units are provided as DNase activity.Clause 67. The animal feed composition according to any of clauses 64 to 66, wherein the at least one nuclease is added at a concentration of at least about 1,000 U / kg of animal feed, preferably at least about 2,000 U / kg, more preferably at least about 5,000 U / kg, still more preferably at least about 6,000 U / kg, still more preferably at least about 7,000 U / kg, still more preferably at least about 8,000 U / kg, still more preferably at least about 9,000 U / kg, still more preferably at least about 10,000 U / kg, still more preferably at least about 11,000 U / kg, still more preferably at least about 12,000 U / kg, still more preferably at least about 13,000 U / kg, still more preferably at least about 14,000 U / kg, even more preferably at least about 15,000 U / kg, yet more preferably at least about 16,000 U / kg and most preferably at least about 16,600 U / kg, wherein the enzyme units are provided as RNase activity.Clause 68. The animal feed composition according to claim 67, wherein the at least one nuclease is added at a concentration ranging from about 1,000 to about 50,000 U / kg of animal feed, from about 2,000 to about 40,000 U / kg, more preferably about 3,000 to about 30,000 U / kg, still more preferably about 4,000 to about 20,000 U / kg, still more preferably about 5,000 to about 18,000 U / kg and particularly preferably at a final concentration ranging from about 6,400 to about 16,687 U / kg, wherein the enzyme units are provided as RNase activity.Clause 69. Use of a feed additive or feed supplement or feed composition according to any of clauses 40 to 68, for improving an animal growth performance, nutrient utilization, gut integrity, and / or resistance or treatment of necrotic enteritis.Clause 70. The use according to clause 69, wherein the animal is a monogastric or a ruminant animal.Clause 71. The use according to clause 70, wherein the monogastric animal is selected from the group consisting of poultry, birds, swine, dogs, cats, fish, shellfish, humans, primates, calves, and horses.Clause 72. The use according to clause 70, wherein the ruminant animal is selected from the group consisting of bovine, sheep, goat, camel, deer, llama, antelope, alpaca, and wildebeest.Clause 73. A method for improving gut integrity and homeostasis, comprising administering to an animal at least one nuclease, wherein the at least one nuclease is administered by means of a feed additive or feed supplement and / or by an animal feed composition.Clause 74. The method according to clause 73, wherein the at least one nuclease is selected from the group consisting of endonucleases, exonucleases, and mixed exo- / endonucleases, preferably selected from endonucleases.Clause 75. The method according to any of clauses 73 to 74, wherein the at least one nuclease has a DNA-degrading activity, an RNA-degrading activity, or a mixed DNA and RNA degrading activity.Clause 76. The method according to any of clauses 73 to 75, wherein the at least one nuclease is selected from the group of enzymes classified under EC classes selected from EC3.1.11, EC3.1.13, EC3.1.14, EC3.1.21, EC3.1.25, EC 3.1.26, EC3.1.27, EC 3.1.30 and EC 3.1.31.Clause 77. The method according to any of clauses 73 to 75, wherein the at least one nuclease is selected from the group of enzymes classified under EC classes selected from EC 3.1.26, EC 3.1.30 and EC 3.1.31.Clause 78. The method according to any of clauses 73 to 77, wherein the at least one nuclease is selected from the group of enzymes classified under EC classes selected from EC 3.1.26 and EC 3.1.30.Clause 79. The method according to clause 76, wherein the at least one nuclease is selected from the group of enzymes classified under EC classes selected from EC 3.1.11.2, EC 3.1.11.5, EC 3.1.11.6, EC 3.1.13.4, EC 3.1.14.1, EC 3.1.21.1, EC 3.1.21.2, EC 3.1.21.3, EC 3.1.21.4, EC 3.1.21.6, EC 3.1.25.1, EC 3.1.26.3, EC 3.1.26.4, EC 3.1.26.5, EC 3.1.26.8, EC 3.1.26.9, EC 3.1.26.11, EC 3.1.27.1, EC 3.1.27.3, EC 3.1.27.5, EC 3.1.30.1, EC 3.1.30.2 and EC 3.1.31.1.Clause 80. The method according to clause 79, wherein the at least one nuclease is selected from the group of enzymes classified under EC classes selected from EC 3.1.26.5 and EC 3.1.30.2.Clause 81. The method according to any of clauses 73 to 80, wherein the at least one nuclease is derived from a microbial origin.Clause 82. The method according to any of clauses 73 to 81, wherein the at least one nuclease is derived from a gram-negative bacterium, preferably selected from the group consisting of Acidithiobacillales, Aeromonadales, Alteromonadales, Cardiobacteriales, Chromatiales, Enterobacterales, Legionellales, Methylococcales, Oceanospirillales, Pasteurellales, Pseudomonadales, Thiotrichales, Vibrionales and Xanthomonadales, more preferably from Enterobacterales.Clause 83. The method according to any of clauses 73 to 82, wherein the at least one nuclease is derived from a genus of the order Enterobacterales, selected from the group consisting of Arsenophonus, Brenneria, Buchnera, Budvicia, Buttiauxella, Cedecea, Citrobacter, Dickeya, Edwardsiella, Enterobacter, Erwinia, Escherichia, Ewingella, Elafnia, Klebsiella, Kluyvera, Leclercia, Leminorella, Moellerella, Marganella, Obesumbacterium, Pantoea, Pectobacterium, Photorhabdus, Plesiomonas, Pragia, Proteus, Providencia, Rahnella, Raoultella, Saccharobacter, Salmonella, Samsonia, Serratia, Shigella, Sodalis, Tatumella, Thorsellia, Trabulsiella, Wigglesworthia, Xenorhabdus, Yersinia and Yokenella, preferably from Serratia.Clause 84. The method according to any of clauses 73 to 83, wherein the at least one nuclease is derived from a species of the genus Serratia selected from the group consisting of Serratia entomophila, Serratia ficaria, Serratia fonticola, Serratia grimesii, Serratia marcescens, Serratia liquefaciens, Serratia odorifera, Serratia plymuthica, Serratia proteamaculans, Serratia quinivorans, Serratia rubidaea and Serratia ureilytica,Clause 85. The method according to any of clauses 73 to 84, wherein the at least one nuclease is derived from Serratia marcescens.Clause 86. The method according to any of clauses 73 to 85, wherein the at least one nuclease is at least 70%, preferably at least 75%, more preferably at least 80%, even more preferably at least 85%, still more preferably at least 90%, still more preferably at least 95%, still more preferably at least 98%, most preferably at least 99%, or in particular at least 100% identical to the sequence of SEQ ID NO: 1 or SEQ ID NO:2.Clause 87. The method according to any of clauses 73 to 81, wherein the at least one nuclease is derived from a fungus selected from the group consisting of Penicillium, Candida, Saccharomyces, and Trichoderma, preferably from Penicillium.Clause 88. The method according to clause 87, wherein the at least one nuclease is derived from Penicillium citrinum.Clause 89. The method according to any of clauses 73 to 88, wherein the at least one nuclease is a recombinant protein.Clause 90. The method according to any of clauses 73 to 89, wherein the at least one nuclease is a functional variant that retains nuclease activity of the reference nuclease.Clause 91. The method according to any of clauses 73 to 90, wherein the functional variant of the nuclease exhibits an improved specific nuclease activity compared to the reference nuclease, as measured under standard test conditions, preferably with the improvement being at least 5%, preferably at least 10%, more preferably at least 20%, even more preferably at least 100%.Clause 92. The method according to any of clauses 73 to 91, wherein the functional variant of the nuclease exhibits an improved thermal stability compared to the reference nuclease, as measured under standard test conditions, preferably with the improvement being at least 5%, preferably at least 10%, more preferably at least 20%, even more preferably at least 100%.Clause 93. The method according to any of clauses 73 to 86 or 89 to 92, wherein the at least one nuclease is at least 70%, preferably at least 75%, more preferably at least 80%, even more preferably at least 85%, still more preferably at least 90%, still more preferably at least 95%, still more preferably at least 98%, most preferably at least 99%, or in particular at least 100% identical to any one of the amino acid sequences SEQ ID NO:3, SEQ ID NO:4 or SEQ ID NO:5.Clause 94. The method according to any of clauses 73 to 93, wherein the at least one nuclease is produced by a fermentation process using a bacterial host cell, preferably selected from Escherichia coli, Bacillus subtilis and Bacillus amyloliquefaciens .Clause 95. The method according to any of clauses 73 to 94, wherein the at least one nuclease is administered at a dosage of at least about 100 U / kg of animal feed, preferably at least about 200 U / kg, more preferably at least about 400 U / kg, still more preferably at least about 800 U / kg, still morepreferably at least about 1,200 U / kg, still more preferably at least about 1,500 U / kg, still more preferably at least about 2,000 U / kg of animal feed, still more preferably at least about 3,000 U / kg, still more preferably at least about 3,500 U / kg, still more preferably at least about 4,000 U / kg, still more preferably at least about 5,000 U / kg, still more preferably at least about 6,000 U / kg, still more preferably at least about 7,000 U / kg, still more preferably at least about 8,000 U / kg, still more preferably at least about 9,000 U / kg, even more preferably at least about 10,000 U / kg, yet more preferably at least about 11,000 U / kg and most preferably at least about 12,000 U / kg, wherein the enzyme units are provided as DNase activity, wherein the dosage is provided through the feed additive, feed supplement, or animal feed composition comprising the feed additive or the feed supplement.Clause 96. The method according to any of clauses 73 to 95, wherein the at least one nuclease is administered at a dosage of at least about 1,000 U / kg of animal feed, preferably at least about 2,000 U / kg, more preferably at least about 5,000 U / kg, still more preferably at least about 6,000 U / kg, still more preferably at least about 7,000 U / kg, still more preferably at least about 8,000 U / kg, still more preferably at least about 9,000 U / kg, still more preferably at least about 10,000 U / kg, still more preferably at least about 11,000 U / kg, still more preferably at least about 12,000 U / kg, still more preferably at least about 13,000 U / kg, still more preferably at least about 14,000 U / kg, even more preferably at least about 15,000 U / kg, yet more preferably at least about 16,000 U / kg and most preferably at least about 16,600 U / kg, wherein the enzyme units are provided as RNase activity, wherein the dosage is provided through the feed additive, feed supplement, or animal feed composition comprising the feed additive or the feed supplement.Clause 97. The method according to clause 95, wherein the at least one nuclease is administered at a dosage ranging from about 100 to about 50,000 U / kg of animal feed, from about 200 to about 40,000 U / kg, more preferably about 300 to about 30,000 U / kg, still more preferably about 390 to about 20,000 U / kg, still more preferably about 390 to about 15,000 U / kg, even more preferably about 390 to about 14,000 U / kg, yet more preferably about 390 to about 12,000 U / kg, and particularly preferably at a final concentration ranging from about 390 to about 11,880 U / kg, wherein the enzyme units are provided as DNase activity, wherein the dosage is provided through the feed additive, feed supplement, or animal feed composition comprising the feed additive or the feed supplement.Clause 98. The method according to clause 96, wherein the at least one nuclease is administered at a dosage ranging from about 1,000 to about 50,000 U / kg of animal feed, from about 2,000 to about 40,000 U / kg, more preferably about 3,000 to about 30,000 U / kg, still more preferably about 4,000 to about 20,000 U / kg, still more preferably about 5,000 to about 18,000 U / kg and particularly preferably at a final concentration ranging from about 6,400 to about 16,687 U / kg, wherein the enzyme units are provided as RNase activity, wherein the dosage is provided through the feed additive, feed supplement, or animal feed composition comprising the feed additive or the feed supplement.Clause 99. The method according to any of clauses 73 to 98, wherein the improved gut integrity is measured in terms of at least one of the following parameters: villi height (VH), crypt depth (CD), villi width (VW), VH:CD ratio (VCR), villi surface area, intestinal lesion score, microbial density and / or presence of pathogenic or non-pathogenic microorganisms / organisms within the digestive system.Clause 100. The method according to any of clauses 73 to 99, wherein a clinical or subclinical intestinal disease challenge is present in the animal.Clause 101. The method according to clause 100, wherein the clinical or subclinical intestinal disease challenge may be caused by a pathogenic bacterium.Clause 102. The method according to any of clauses 100 and 101, wherein the pathogenic bacterium is Clostridium perfringens.Clause 103. The method according to any of clauses 100 to 102, wherein the clinical or subclinical intestinal disease challenge includes additionally a challenge with Eimeria species.Clause 104. The method according to any of clauses 100 to 103, wherein the feed additive or feed supplement or feed composition further comprises a suitable carrier.Clause 105. The method according to any of clauses 73 to 104, wherein the feed additive or feed supplement or feed composition further comprises at least one feed additive, wherein the at least one further feed additive is an enzyme selected from the group of phytases, carbohydrases, and proteases.Clause 106. The method according to any of clauses 73 to 105, wherein the animal is a monogastric animal or a ruminant animal.Clause 107. The method according to clause 106, wherein the monogastric animal is selected from the group consisting of birds, swine, dogs, cats, fish, shellfish, humans, primates, calves, and horses.Clause 108. The method according to clause 106, wherein the ruminant animal is selected from the group consisting of bovine, sheep, goat, camel, deer, llama, antelope, alpaca, and wildebeest.Clause 109. A method for improving gut integrity, comprising administering to an animal at least one nuclease, wherein the at least one nuclease is administered by means of a feed additive or feed supplement or by an animal feed composition comprising the feed additive or the feed supplement.Clause 110. The method according to clause 109, wherein the at least one nuclease is selected from the group consisting of endonucleases, exonucleases, and mixed exo- / endonucleases, preferably selected from endonucleases.Clause 111. The method according to any of clauses 109 and 110, wherein the at least one nuclease has a DNA-degrading activity, an RNA-degrading activity, or a mixed DNA and RNA degrading activity.Clause 112. The method according to any one of clauses 109 to 111, wherein the at least one nuclease is selected from the group of enzymes classified under EC classes selected from EC3.1.11, EC3.1.13, EC3.1.14, EC3.1.21, EC3.1.25, EC 3.1.26, EC3.1.27, EC 3.1.30 and EC 3.1.31.Clause 113. The method according to any one of clauses 109 to 112, wherein the at least one nuclease is selected from the group of enzymes classified under EC classes selected from EC 3.1.26, EC 3.1.30 and EC 3.1.31.Clause 114. The method according to any one of clauses 109 to 113, wherein the at least one nuclease is selected from the group of enzymes classified under EC classes selected from EC 3.1.26 and EC 3.1.30.Clause 115. The method according to clause 112, wherein the at least one nuclease is selected from the group of enzymes classified under EC classes selected from EC 3.1.11.2, EC 3.1.11.5, EC 3.1.11.6, EC 3.1.13.4, EC 3.1.14.1, EC 3.1.21.1, EC 3.1.21.2, EC 3.1.21.3, EC 3.1.21.4, EC 3.1.21.6, EC 3.1.25.1, EC 3.1.26.3, EC 3.1.26.4, EC 3.1.26.5, EC 3.1.26.8, EC 3.1.26.9, EC 3.1.26.11, EC 3.1.27.1, EC 3.1.27.3, EC 3.1.27.5, EC 3.1.30.1, EC 3.1.30.2 and EC 3.1.31.1.Clause 116. The method according to any of clause 115, wherein the at least one nuclease is selected from the group of enzymes classified under EC classes selected from EC 3.1.26.5 and EC 3.1.30.2.Clause 117. The method according to any of clauses 109 to 116, wherein the at least one nuclease is derived from a microbial origin.Clause 118. The method according to any of clauses 109 to 117, wherein the at least one nuclease is derived from a gram-negative bacterium, preferably selected from the group consisting of Acidithiobacillales, Aeromonadales, Alteromonadales, Cardiobacteriales, Chromatiales, Enterobacterales, Legionellales, Methylococcales, Oceanospirillales, Pasteurellales, Pseudomonadales, Thiotrichales, Vibrionales and Xanthomonadales, more preferably from Enterobacterales.Clause 119. The method according to any of clauses 109 to 118, wherein the at least one nuclease is derived from a genus of the order Enterobacterales, selected from the group consisting of Arsenophonus, Brenneria, Buchnera, Budvicia, Buttiauxella, Cedecea, Citrobacter, Dickeya, Edwardsiella, Enterobacter, Erwinia, Escherichia, Ewingella, Elafnia, Klebsiella, Kluyvera, Leclercia, Leminorella, Moellerella, Marganella, Obesumbacterium, Pantoea, P ectobacterium, Photorhabdus, Plesiomonas, Pragia, Proteus, Providencia, Rahnella, Raoultella, Saccharobacter, Salmonella, Samsonia, Serratia, Shigella, Sodalis, Tatumella, Thorsellia, Trabulsiella, Wigglesworthia, Xenorhabdus, Yersinia and Yokenella, preferably from Serratia.Clause 120. The method according to any of clauses 109 to 119, wherein the at least one nuclease is derived from a species of the genus Serratia selected from the group consisting of Serratia entomophila, Serratia ficaria, Serratia fonticola, Serratia grimesii, Serratia marcescens, Serratia liquefaciens, Serratia odorifera, Serratia plymuthica, Serratia proteamaculans, Serratia quinivorans, Serratia rubidaea and Serratia ureilytica,Clause 121. The method according to any of clauses 109 to 120, wherein the at least one nuclease is derived from Serratia marcescens.Clause 122. The method according to any of clauses 109 to 121, wherein the at least one nuclease is at least 70%, preferably at least 75%, more preferably at least 80%, even more preferably at least 85%, still more preferably at least 90%, still more preferably at least 95%, still more preferably at least 98%, most preferably at least 99%, or in particular at least 100% identical to the sequence of SEQ ID NO:1 or SEQ ID NO:2.Clause 123. The method according to any of clauses 109 to 117, wherein the at least one nuclease is derived from a fungus selected from the group consisting of Penicillium, Candida, Saccharomyces, and Trichoderma, preferably from Penicillium.Clause 124. The method according to clause 123, wherein the at least one nuclease is derived from Penicillium citrinum.Clause 125. The method according to any of clauses 109 to 124, wherein the at least one nuclease is a recombinant protein.Clause 126. The method according to any of clauses 109 to 125, wherein the at least one nuclease is a functional variant that retains nuclease activity of the reference nuclease.Clause 127. The method according to clause 126, wherein the functional variant of the nuclease exhibits an improved specific nuclease activity compared to the reference nuclease, as measured under standard test conditions, preferably with the improvement being at least 5%, preferably at least 10%, more preferably at least 20%, even more preferably at least 100%.Clause 128. The method according to any of clauses 126 and 127, wherein the functional variant of the nuclease exhibits an improved thermal stability compared to the reference nuclease, as measured under standard test conditions, preferably with the improvement being at least 5%, preferably at least 10%, more preferably at least 20%, even more preferably at least 100%.Clause 129. The method according to any of clauses 109 to 122 or 125 to 128, wherein the at least one nuclease is at least 70%, preferably at least 75%, more preferably at least 80%, even more preferably at least 85%, still more preferably at least 90%, still more preferably at least 95%, still more preferably at least 98%, most preferably at least 99%, or in particular at least 100% identical to any one of the amino acid sequences SEQ ID NO:3, SEQ ID NO:4 or SEQ ID NO:5.Clause 130. The method according to any of clauses 109 to 129, wherein the at least one nuclease is produced by a fermentation process using a bacterial host cell, preferably selected from Escherichia coli, Bacillus subtilis and Bacillus amyloliquefaciens .Clause 131. The method according to any of clauses 109 to 130, wherein the at least one nuclease is administered at a dosage of at least about 100 U / kg of animal feed, preferably at least about 200 U / kg, more preferably at least about 400 U / kg, still more preferably at least about 800 U / kg, still more preferably at least about 1,200 U / kg, still more preferably at least about 1,500 U / kg, still more preferably at least about 2,000 U / kg of animal feed, still more preferably at least about 3,000 U / kg, stillmore preferably at least about 3,500 U / kg, still more preferably at least about 4,000 U / kg, still more preferably at least about 5,000 U / kg, still more preferably at least about 6,000 U / kg, still more preferably at least about 7,000 U / kg, still more preferably at least about 8,000 U / kg, still more preferably at least about 9,000 U / kg, even more preferably at least about 10,000 U / kg, yet more preferably at least about 11,000 U / kg and most preferably at least about 12,000 U / kg, wherein the enzyme units are provided as DNase activity, wherein the dosage is provided through the feed additive, feed supplement, or animal feed composition comprising the feed additive or the feed supplement.Clause 132. The method according to any of clauses 109 to 131, wherein the at least one nuclease is administered at a dosage of at least about 1,000 U / kg of animal feed, preferably at least about 2,000 U / kg, more preferably at least about 5,000 U / kg, still more preferably at least about 6,000 U / kg, still more preferably at least about 7,000 U / kg, still more preferably at least about 8,000 U / kg, still more preferably at least about 9,000 U / kg, still more preferably at least about 10,000 U / kg, still more preferably at least about 11,000 U / kg, still more preferably at least about 12,000 U / kg, still more preferably at least about 13,000 U / kg, still more preferably at least about 14,000 U / kg, even more preferably at least about 15,000 U / kg, yet more preferably at least about 16,000 U / kg and most preferably at least about 16,600 U / kg, wherein the enzyme units are provided as RNase activity, wherein the dosage is provided through the feed additive, feed supplement, or animal feed composition comprising the feed additive or the feed supplement.Clause 133. The method according to clause 131, wherein the at least one nuclease is administered at a dosage ranging from about 100 to about 50,000 U / kg of animal feed, from about 200 to about 40,000 U / kg, more preferably about 300 to about 30,000 U / kg, still more preferably about 390 to about 20,000 U / kg, still more preferably about 390 to about 15,000 U / kg, even more preferably about 390 to about 14,000 U / kg, yet more preferably about 390 to about 12,000 U / kg, and particularly preferably at a final concentration ranging from about 390 to about 11,880 U / kg, wherein the enzyme units are provided as DNase activity, wherein the dosage is provided through the feed additive, feed supplement, or animal feed composition comprising the feed additive or the feed supplement.Clause 134. The method according to clause 132, wherein the at least one nuclease is administered at a dosage ranging from about 1,000 to about 50,000 U / kg of animal feed, from about 2,000 to about 40,000 U / kg, more preferably about 3,000 to about 30,000 U / kg, still more preferably about 4,000 to about 20,000 U / kg, still more preferably about 5,000 to about 18,000 U / kg and particularly preferably at a final concentration ranging from about 6,400 to about 16,687 U / kg, wherein the enzyme units are provided as RNase activity, wherein the dosage is provided through the feed additive, feed supplement, or animal feed composition comprising the feed additive or the feed supplement.Clause 135. The method according to any of clauses 109 to 134, wherein the improved gut integrity is measured in terms of at least one of the following parameters: villi height (VH), crypt depth (CD), villi width (VW), VH:CD ratio (VCR), villi surface area, intestinal lesion score, microbial densityand / or presence of pathogenic or non-pathogenic microorganisms / organisms within the digestive system.Clause 136. The method according to any of clauses 109 to 135, wherein a clinical or subclinical intestinal disease challenge is present in the animal.Clause 137. The method according to clause 136, wherein the clinical or subclinical intestinal disease challenge may be caused by a pathogenic bacterium.Clause 138. The method according to any of clauses 136 and 137, wherein the pathogenic bacterium is Clostridium perfringens.Clause 139. The method according to any of clauses 136 to 138, wherein the clinical or subclinical intestinal disease challenge includes additionally a challenge with Eimeria species.Clause 140. The method according to any of clauses 109 to 139, wherein the feed additive or feed supplement or feed composition further comprises a suitable carrier.Clause 141. The method according to any of clauses 109 to 140, wherein the feed additive or feed supplement or feed composition further comprises at least one feed additive, wherein the at least one further feed additive is an enzyme selected from the group of phytases, carbohydrases, and proteases.Clause 142. The method according to any of clauses 109 to 142, wherein the animal is a monogastric animal or a ruminant animal.Clause 143. The method according to clause 142, wherein the monogastric animal is selected from the group consisting of birds, swine, dogs, cats, fish, shellfish, humans, primates, calves, and horses.Clause 144. The method according to clause 142, wherein the ruminant animal is selected from the group consisting of bovine, sheep, goat, camel, deer, llama, antelope, alpaca, and wildebeest.Clause 145. A method for treatment or amelioration of subacute necrotic enteritis, comprising administering to an animal at least one nuclease, wherein the at least one nuclease is administered by means of a feed additive or feed supplement or by an animal feed composition comprising the feed additive or the feed supplement.Clause 146. The method according to clause 145, wherein the at least one nuclease is selected from the group consisting of endonucleases, exonucleases, and mixed exo- / endonucleases, preferably selected from endonucleases.Clause 147. The method according to clause 145 or clause 146, wherein the at least one nuclease has a DNA-degrading activity, an RNA-degrading activity, or a mixed DNA and RNA degrading activity.Clause 148. The method according to any of clauses 145 to 147, wherein the at least one nuclease is selected from the group of enzymes classified under EC classes selected from EC3.1.11, EC3.1.13, EC3.1.14, EC3.1.21, EC3.1.25, EC 3.1.26, EC3.1.27, EC 3.1.30 and EC 3.1.31.Clause 149. The method according to any of clauses 145 to 148, wherein the at least one nuclease is selected from the group of enzymes classified under EC classes selected from EC 3.1.26, EC 3.1.30 and EC 3.1.31.Clause 150. The method according to any of clauses 145 to 149, wherein the at least one nuclease is selected from the group of enzymes classified under EC classes selected from EC 3.1.26 and EC 3.1.30.Clause 151. The method according to clause 148, wherein the at least one nuclease is selected from the group of enzymes classified under EC classes selected from EC 3.1.11.2, EC 3.1.11.5, EC 3.1.11.6, EC 3.1.13.4, EC 3.1.14.1, EC 3.1.21.1, EC 3.1.21.2, EC 3.1.21.3, EC 3.1.21.4, EC 3.1.21.6, EC 3.1.25.1, EC 3.1.26.3, EC 3.1.26.4, EC 3.1.26.5, EC 3.1.26.8, EC 3.1.26.9, EC 3.1.26.11, EC 3.1.27.1, EC 3.1.27.3, EC 3.1.27.5, EC 3.1.30.1, EC 3.1.30.2 and EC 3.1.31.1.Clause 152. The method according to clause 151, wherein the at least one nuclease is selected from the group of enzymes classified under EC classes selected from EC 3.1.26.5 and EC 3.1.30.2.Clause 153. The method according to any of clauses 145 to 152, wherein the at least one nuclease is derived from a microbial origin.Clause 154. The method according to any of clauses 145 to 153, wherein the at least one nuclease is derived from a gram-negative bacterium, preferably selected from the group consisting of Acidithiobacillales, Aeromonadales, Alteromonadales, Cardiobacteriales, Chromatiales, Enterobacterales, Legionellales, Methylococcales, Oceanospirillales, Pasteurellales, Pseudomonadales, Thiotrichales, Vibrionales and Xanthomonadales, more preferably from Enterobacterales.Clause 155. The method according to any of clauses 145 to 154, wherein the at least one nuclease is derived from a genus of the order Enterobacterales, selected from the group consisting of Arsenophonus, Brenneria, Buchnera, Budvicia, Buttiauxella, Cedecea, Citrobacter, Dickeya, Edwardsiella, Enterobacter, Erwinia, Escherichia, Ewingella, Elafnia, Klebsiella, Kluyvera, Leclercia, Leminorella, Moellerella, Marganella, Obesumbacterium, Pantoea, P ectobacterium, Photorhabdus, Plesiomonas, Pragia, Proteus, Providencia, Rahnella, Raoultella, Saccharobacter, Salmonella, Samsonia, Serratia, Shigella, Sodalis, Tatumella, Thorsellia, Trabulsiella, Wigglesworthia, Xenorhabdus, Yersinia and Yokenella, preferably from Serratia.Clause 156. The method according to any of clauses 145 to 155, wherein the at least one nuclease is derived from a species of the genus Serratia selected from the group consisting of Serratia entomophila, Serratia ficaria, Serratia fonticola, Serratia grimesii, Serratia marcescens, Serratia liquefaciens, Serratia odorifera, Serratia plymuthica, Serratia proteamaculans, Serratia quinivorans, Serratia rubidaea and Serratia ureilytica,Clause 157. The method according to any of clauses 145 to 156, wherein the at least one nuclease is derived from Serratia marcescens.Clause 158. The method according to any of clauses 145 to 157, wherein the at least one nuclease is at least 70%, preferably at least 75%, more preferably at least 80%, even more preferably at least 85%, still more preferably at least 90%, still more preferably at least 95%, still more preferably at least 98%, most preferably at least 99%, or in particular at least 100% identical to the sequence of SEQ ID NO:1 or SEQ ID NO:2.Clause 159. The method according to any of clauses 145 to 153, wherein the at least one nuclease is derived from a fungus selected from the group consisting of Penicillium, Candida, Saccharomyces, and Trichoderma, preferably from Penicillium.Clause 160. The method according to clause 159, wherein the at least one nuclease is derived from Penicillium citrinum.Clause 161. The method according to any of clauses 145 to 160, wherein the at least one nuclease is a recombinant protein.Clause 162. The method according to any of clauses 145 to 162, wherein the at least one nuclease is a functional variant that retains nuclease activity of the reference nuclease.Clause 163. The method according to clause 162, wherein the functional variant of the nuclease exhibits an improved specific nuclease activity compared to the reference nuclease, as measured under standard test conditions, preferably with the improvement being at least 5%, preferably at least 10%, more preferably at least 20%, even more preferably at least 100%.Clause 164. The method according to any of clauses 162 and 163, wherein the functional variant of the nuclease exhibits an improved thermal stability compared to the reference nuclease, as measured under standard test conditions, preferably with the improvement being at least 5%, preferably at least 10%, more preferably at least 20%, even more preferably at least 100%.Clause 165. The method according to any of clauses 145 to 158 or 161 to 164, wherein the at least one nuclease is at least 70%, preferably at least 75%, more preferably at least 80%, even more preferably at least 85%, still more preferably at least 90%, still more preferably at least 95%, still more preferably at least 98%, most preferably at least 99%, or in particular at least 100% identical to any one of the amino acid sequences SEQ ID NO:3, SEQ ID NO:4 or SEQ ID NO:5.Clause 166. The method according to any of clauses 145 to 165, wherein the at least one nuclease is produced by a fermentation process using a bacterial host cell, preferably selected from Escherichia coli, Bacillus subtilis and Bacillus amyloliquefaciens .Clause 167. The method according to any of clauses 145 to 166, wherein the at least one nuclease is administered at a dosage of at least about 100 U / kg of animal feed, preferably at least about 200 U / kg, more preferably at least about 400 U / kg, still more preferably at least about 800 U / kg, still more preferably at least about 1,200 U / kg, still more preferably at least about 1,500 U / kg, still more preferably at least about 2,000 U / kg of animal feed, still more preferably at least about 3,000 U / kg, stillmore preferably at least about 3,500 U / kg, still more preferably at least about 4,000 U / kg, still more preferably at least about 5,000 U / kg, still more preferably at least about 6,000 U / kg, still more preferably at least about 7,000 U / kg, still more preferably at least about 8,000 U / kg, still more preferably at least about 9,000 U / kg, even more preferably at least about 10,000 U / kg, yet more preferably at least about 11,000 U / kg and most preferably at least about 12,000 U / kg, wherein the enzyme units are provided as DNase activity, wherein the dosage is provided through the feed additive, feed supplement, or animal feed composition comprising the feed additive or the feed supplement.Clause 168. The method according to any of clauses 145 to 167, wherein the at least one nuclease is administered at a dosage of at least about 1,000 U / kg of animal feed, preferably at least about 2,000 U / kg, more preferably at least about 5,000 U / kg, still more preferably at least about 6,000 U / kg, still more preferably at least about 7,000 U / kg, still more preferably at least about 8,000 U / kg, still more preferably at least about 9,000 U / kg, still more preferably at least about 10,000 U / kg, still more preferably at least about 11,000 U / kg, still more preferably at least about 12,000 U / kg, still more preferably at least about 13,000 U / kg, still more preferably at least about 14,000 U / kg, even more preferably at least about 15,000 U / kg, yet more preferably at least about 16,000 U / kg and most preferably at least about 16,600 U / kg, wherein the enzyme units are provided as RNase activity, wherein the dosage is provided through the feed additive, feed supplement, or animal feed composition comprising the feed additive or the feed supplement.Clause 169. The method according to clause 167, wherein the at least one nuclease is administered at a dosage ranging from about 100 to about 50,000 U / kg of animal feed, from about 200 to about 40,000 U / kg, more preferably about 300 to about 30,000 U / kg, still more preferably about 390 to about 20,000 U / kg, still more preferably about 390 to about 15,000 U / kg, even more preferably about 390 to about 14,000 U / kg, yet more preferably about 390 to about 12,000 U / kg, and particularly preferably at a final concentration ranging from about 390 to about 11,880 U / kg, wherein the enzyme units are provided as DNase activity, wherein the dosage is provided through the feed additive, feed supplement, or animal feed composition comprising the feed additive or the feed supplement.Clause 170. The method according to clause 168, wherein the at least one nuclease is administered at a dosage ranging from about 1,000 to about 50,000 U / kg of animal feed, from about 2,000 to about 40,000 U / kg, more preferably about 3,000 to about 30,000 U / kg, still more preferably about 4,000 to about 20,000 U / kg, still more preferably about 5,000 to about 18,000 U / kg and particularly preferably at a final concentration ranging from about 6,400 to about 16,687 U / kg, wherein the enzyme units are provided as RNase activity, wherein the dosage is provided through the feed additive, feed supplement, or animal feed composition comprising the feed additive or the feed supplement.Clause 171. The method according to any of clauses 145 to 170, wherein the treatment or amelioration of subacute necrotic enteritis is measured in terms of at least one of the following parameters: improved feed conversion ratio (FCR), improved body weight adjusted feed conversionratio (bwFCR), improved growth rate, improved body weight gain (BWG), improved European Production Efficiency Factor (EPEF), reduced mortality rate, improved nutrient retention (NR), improved metabolizable energy digestibility, improved nitrogen-corrected apparent metabolizable energy (AMEn), improved crude protein digestibility, reduced intestinal lesion score, improved villi height (VH), improved villi width (VW), improved crypt depth (CD), improved VH:CD ratio (VCR), improved villi surface area and / or reduced presence of pathogenic microorganisms / organisms within the digestive system.Clause 172. The method according to any of clauses 145 to 171, wherein a clinical or subclinical intestinal disease challenge is present in the animal.Clause 173. The method according to clause 172, wherein the clinical or subclinical intestinal disease challenge may be caused by a pathogenic bacterium.Clause 174. The method according to any of clauses 172 and 173, wherein the pathogenic bacterium is Clostridium perfringens.Clause 175. The method according to any of clauses 172 to 174, wherein the clinical or subclinical intestinal disease challenge includes additionally a challenge with Eimeria species.Clause 176. The method according to any of clauses 145 to 175, wherein the feed additive or feed supplement or feed composition further comprises a suitable carrier.Clause 177. The method according to any of clauses 145 to 176, wherein the feed additive or feed supplement or feed composition further comprises at least one feed additive, wherein the at least one further feed additive is an enzyme selected from the group of phytases, carbohydrases, and proteases.Clause 178. The method according to any of clauses 145 to 177, wherein the animal is a monogastric animal or a ruminant animal.Clause 179. The method according to clause 178, wherein the monogastric animal is selected from the group consisting of birds, swine, dogs, cats, fish, shellfish, humans, primates, calves, and horses.Clause 180. The method according to clause 178, wherein the ruminant animal is selected from the group consisting of bovine, sheep, goat, camel, deer, llama, antelope, alpaca, and wildebeest.Clause 181. A feed additive or feed supplement comprising at least one nuclease.Clause 182. The feed additive or feed supplement according to clause 181, wherein the at least one nuclease is an endonuclease.Clause 183. The feed additive or feed supplement according to clause 181 or 182, wherein the at least one nuclease has a DNA-de grading activity, a RNA-degrading activity, or a mixed DNA and RNA degrading activity.Clause 184. The feed additive or feed supplement according to any of clauses 181 to 183, wherein the at least one nuclease is a nuclease pertaining to a EC class selected from EC EC class 3.1.30, and EC class 3.1.26.Clause 185. The feed additive or feed supplement according to any of clauses 181 to 184, wherein the at least one nuclease is of microbial origin and / or is a recombinant protein.Clause 186. The feed additive or feed supplement according to any of clauses 181 to 185, wherein the at least one nuclease is derived from a gram-negative bacterium.Clause 187. The feed additive or feed supplement according to clause 181, wherein the gramnegative bacterium is Serratia marcescens.Clause 188. The feed additive or feed supplement according to any of clauses 181 to 187, wherein the at least one nuclease is derived from a fungus.Clause 189. The feed additive or feed supplement according to clause 181, wherein the fungus is Penicillium citrinum.Clause 190. The feed additive or feed supplement according to any of clauses 181 to 189, wherein the at least one nuclease is a recombinant protein.Clause 191. The feed additive or feed supplement according to any of clauses 181 to 190, wherein the at least one nuclease comprises an amino acid sequence having at least 70 % identity to SEQ ID NO: 1, and / or SEQ ID NO: 2, preferably an amino acid sequence having at least 80 % identity to SEQ ID NO: 2.Clause 192. The feed additive or feed supplement according to any of clauses 181 to 191, wherein the enzyme food or feed additive improves the utilization of nucleic acids by resident microbiome in the gastrointestinal tract of an animal.Clause 193. The feed additive or feed supplement according to any of clauses 181 to 192, further comprising a suitable carrier agent.Clause 194. The feed additive or feed supplement according to any of clauses 181 to 193, further comprising at least one feed additive, wherein the further feed additive is a phytase enzyme.Clause 195. Use of an feed additive or feed supplement according to any of clauses 181 to 194 for improving utilization of nucleic acids by resident microbiome in the gastrointestinal tract of an animal.Clause 196. The use according to clause 195, wherein the animal is a monogastric or a ruminant animal.Clause 197. The use according to clause 196, wherein the monogastric animal is selected from the group consisting of poultry, birds, swine, dogs, cats, fish, shellfish, humans, primates, calves, and horses.Clause 198. The use according to clause 196, wherein the ruminant animal is selected from the group consisting of bovine, sheep, goat, camel, deer, llama, antelope, alpaca, and wildebeest.Clause 199. The use according to any one of clauses 195 to 198, wherein the enzyme food or feed additive is added to an animal feed composition.Clause 200. An animal feed composition comprising the feed additive or feed supplement of any one of clauses 181 to 194.Clause 201. The animal feed composition according to clause 200, wherein at least one nuclease is added to the animal feed at a concentration ranging from 1,000 to 100,000 enzyme units per kilogram of animal feed (U / kg), preferably ranging from 19,800 to 59,400 U / kg.Clause 202. A method of improving an animal growth performance, nutrient utilization, health, welfare and / or related physiological processes comprising administering at least one nuclease to the animal, wherein the at least one nuclease is administered to the animal by means of the feed additive or feed supplement of any one of clauses 181 to 194 and / or the animal feed composition of clauses 200 to 201.Clause 203. The method of clause 202, wherein the animal growth performance is measured in terms of feed conversion ratio (FCR), growth rate, European Production Efficiency Factor (EPEF), mortality rate, together with associated metrics related to nutrient utilization, for example nutrient retention (NR), metabolizable energy digestibility, nitrogen-corrected apparent metabolizable energy (AMEn), and / or crude protein digestibility.Clause 204. A method of improving an animal gut integrity and homeostasis comprising administering to the animal the feed additive or feed supplement of any one of clauses 181 to 194 and / or the animal feed composition of clauses 200 and 201.Clause 205. The method of clause 204, wherein the gut integrity and homeostasis are measured in terms of villi height (VH), crypt depth (CD), VH:CD ratio, intestinal lesion score, microbial density, metabolic activity in the gastrointestinal tract and / or presence of pathogenic or non-pathogenic microorganisms / organisms within the digestive system.Clause 206. The method according to any one of clauses 204 to 205, wherein the animal is a monogastric or a ruminant animal.Clause 207. The method according to clause 206, wherein the monogastric animal is selected from the group consisting of poultry, birds, swine, dogs, cats, fish, shellfish, humans, primates, calves, and horses.Clause 208. The method according to clause 206, wherein the ruminant animal is selected from the group consisting of bovine, sheep, goat, camel, deer, llama, antelope, alpaca, and wildebeest.Clause 209. The method according to any one of the clauses 204 to 208, wherein the at least one nuclease is administered to an animal at a dosage ranging from 1,000 to 100,000 enzyme units per gram of animal feed (U / g), preferably ranging from 19,800 to 59,400 U / g.Clause 210. A feed additive or a feed supplement or an animal feed composition for use in a method for treating or ameliorating subacute necrotic enteritis in an animal, wherein the method comprises administering to the animal at least one nuclease, wherein the at least one nuclease is administered bymeans of the feed additive or feed supplement of any one of clauses 181 to 194 or by means of the animal feed composition of any one of clause 200 or 201.Clause 211. The feed additive or the feed supplement or the animal feed composition for use according to clause 210, wherein the at least one nuclease is selected from the group consisting of endonucleases, exonucleases, and mixed exo- / endonucleases, preferably selected from endonucleases. Clause 212. The feed additive or the feed supplement or the animal feed composition for use of any one of clause 210 or 211, wherein the at least one nuclease has a DNA-degrading activity, an RNA- degrading activity, or a mixed DNA and RNA degrading activity.Clause 213. The feed additive or the feed supplement or the animal feed composition for use of any one of clauses 210 to 212, wherein the at least one nuclease is selected from the group of enzymes classified under EC classes selected from EC3.1.11, EC3.1.13, EC3.1.14, EC3.1.21, EC3.1.25, EC 3.1.26, EC3.1.27, EC 3.1.30 and EC 3.1.31.Clause 214. The feed additive or the feed supplement or the animal feed composition for use of any one of clauses 210 to 213, wherein the at least one nuclease is selected from the group of enzymes classified under EC classes selected from EC 3.1.26, EC 3.1.30 and EC 3.1.31.Clause 215. The feed additive or the feed supplement or the animal feed composition for use of any one of clauses 210 to 214, wherein the at least one nuclease is selected from the group of enzymes classified under EC classes selected from EC 3.1.26 and EC 3.1.30.Clause 216. The feed additive or the feed supplement or the animal feed composition for use according to clause 213, wherein the at least one nuclease is selected from the group of enzymes classified under EC classes selected from EC 3.1.11.2, EC 3.1.11.5, EC 3.1.11.6, EC 3.1.13.4, EC 3.1.14.1, EC 3.1.21.1, EC 3.1.21.2, EC 3.1.21.3, EC 3.1.21.4, EC 3.1.21.6, EC 3.1.25.1, EC 3.1.26.3, EC 3.1.26.4, EC 3.1.26.5, EC 3.1.26.8, EC 3.1.26.9, EC 3.1.26.11, EC 3.1.27.1, EC 3.1.27.3, EC 3.1.27.5, EC 3.1.30.1, EC 3.1.30.2 and EC 3.1.31.1.Clause 217. The feed additive or the feed supplement or the animal feed composition for use according to clause 216, wherein the at least one nuclease is selected from the group of enzymes classified under EC classes selected from EC 3.1.26.5 and EC 3.1.30.2.Clause 218. The feed additive or the feed supplement or the animal feed composition for use of any one of clauses 210 to 217, wherein the at least one nuclease is derived from a microbial origin.Clause 219. The feed additive or the feed supplement or the animal feed composition for use of any one of clauses 210 to 218, wherein the at least one nuclease is derived from a gram-negative bacterium, preferably selected from the group consisting of Acidithiobacillales, Aeromonadales, Alteromonadales, Cardiobacteriales, Chromatiales, Enterobacterales, Legionellales, Methylococcales, Oceanospirillales, Pasteurellales, Pseudomonadales, Thiotrichales, Vibrionales and Xanthomonadales, more preferably from Enterobacterales.Clause 220. The feed additive or the feed supplement or the animal feed composition for use of any one of clauses 210 to 219, wherein the at least one nuclease is derived from a genus of the orderEnterobacterales, selected from the group consisting of Arsenophonus, Brenneria, Buchnera, Budvicia, Buttiauxella, Cedecea, Citrobacter, Dickeya, Edwardsiella, Enterobacter, Erwinia, Escherichia, Ewingella, Elafnia, Klebsiella, Kluyvera, Leclercia, Leminorella, Moellerella, Marganella, Obesumbacterium, Pantoea, P ectobacterium, Photorhabdus, Plesiomonas, Pragia, Proteus, Providencia, Rahnella, Raoultella, Saccharobacter, Salmonella, Samsonia, Serratia, Shigella, Sodalis, Tatumella, Thorsellia, Trabulsiella, Wigglesworthia, Xenorhabdus, Yersinia and Yokenella, preferably from Serratia.Clause 221. The feed additive or the feed supplement or the animal feed composition for use of any one of clauses 210 to 220, wherein the at least one nuclease is derived from a species of the genus Serratia selected from the group consisting of Serratia entomophila, Serratia ficaria, Serratia fonticola, Serratia grimesii, Serratia marcescens, Serratia liquefaciens, Serratia odorifera, Serratia plymuthica, Serratia proteamaculans, Serratia quinivorans, Serratia rubidaea and Serratia ureilytica,Clause 222. The feed additive or the feed supplement or the animal feed composition for use of any one of clauses 210 to 221, wherein the at least one nuclease is derived from Serratia marcescens.Clause 223. The feed additive or the feed supplement or the animal feed composition for use of any one of clauses 210 to 222, wherein the at least one nuclease is at least 70%, preferably at least 75%, more preferably at least 80%, even more preferably at least 85%, still more preferably at least 90%, still more preferably at least 95%, still more preferably at least 98%, most preferably at least 99%, or in particular at least 100% identical to the sequence of SEQ ID NO: 1 or SEQ ID NO:2.Clause 224. The feed additive or the feed supplement or the animal feed composition for use of any one of clauses 210 to 218, wherein the at least one nuclease is derived from a fungus selected from the group consisting of Penicillium, Candida, Saccharomyces, and Trichoderma, preferably from Penicillium.Clause 225. The feed additive or the feed supplement or the animal feed composition for use according to clause 224, wherein the at least one nuclease is derived from Penicillium citrinum.Clause 226. The feed additive or the feed supplement or the animal feed composition for use of any one of clauses 210 to 225, wherein the at least one nuclease is a recombinant protein.Clause 227. The feed additive or the feed supplement or the animal feed composition for use of any one of clauses 210 to 226, wherein the at least one nuclease is a functional variant that retains nuclease activity of the reference nuclease.Clause 228. The feed additive or the feed supplement or the animal feed composition for use according to clause 227, wherein the functional variant of the nuclease exhibits an improved specific nuclease activity compared to the reference nuclease, as measured under standard test conditions, preferably with the improvement being at least 5%, preferably at least 10%, more preferably at least 20%, even more preferably at least 100%.Clause 229. The feed additive or the feed supplement or the animal feed composition for use according to clause 227 or 228, wherein the functional variant of the nuclease exhibits an improvedthermal stability compared to the reference nuclease, as measured under standard test conditions, preferably with the improvement being at least 5%, preferably at least 10%, more preferably at least 20%, even more preferably at least 100%.Clause 230. The feed additive or the feed supplement or the animal feed composition for use according to any one of clauses 210 to 222 or 226 to 229, wherein the at least one nuclease is at least 70%, preferably at least 75%, more preferably at least 80%, even more preferably at least 85%, still more preferably at least 90%, still more preferably at least 95%, still more preferably at least 98%, most preferably at least 99%, or in particular at least 100% identical to any one of the amino acid sequences SEQ ID NO:3, SEQ ID NO:4 or SEQ ID NO:5.Clause 231. The feed additive or the feed supplement or the animal feed composition for use of any one of clauses 210 to 230, wherein the at least one nuclease is produced by a fermentation process using a bacterial host cell, preferably selected from Escherichia coli, Bacillus subtilis and Bacillus amyloliquefaciens .Clause 232. The feed additive or the feed supplement or the animal feed composition for use of any one of clauses 210 to 231, wherein the at least one nuclease is administered at a dosage of at least about 100 U / kg of animal feed, preferably at least about 200 U / kg, more preferably at least about 400 U / kg, still more preferably at least about 800 U / kg, still more preferably at least about 1,200 U / kg, still more preferably at least about 1,500 U / kg, still more preferably at least about 2,000 U / kg of animal feed, still more preferably at least about 3,000 U / kg, still more preferably at least about 3,500 U / kg, still more preferably at least about 4,000 U / kg, still more preferably at least about 5,000 U / kg, still more preferably at least about 6,000 U / kg, still more preferably at least about 7,000 U / kg, still more preferably at least about 8,000 U / kg, still more preferably at least about 9,000 U / kg, even more preferably at least about 10,000 U / kg, yet more preferably at least about 11,000 U / kg and most preferably at least about 12,000 U / kg, wherein the enzyme units are provided as DNase activity, wherein the dosage is provided through the feed additive, feed supplement, or animal feed composition comprising the feed additive or the feed supplement.Clause 233. The feed additive or the feed supplement or the animal feed composition for use of any one of clauses 210 to 232, wherein the at least one nuclease is administered at a dosage of at least aboutI,000 U / kg of animal feed, preferably at least about 2,000 U / kg, more preferably at least about5,000 U / kg, still more preferably at least about 6,000 U / kg, still more preferably at least about7,000 U / kg, still more preferably at least about 8,000 U / kg, still more preferably at least about9,000 U / kg, still more preferably at least about 10,000 U / kg, still more preferably at least aboutI I,000 U / kg, still more preferably at least about 12,000 U / kg, still more preferably at least about13,000 U / kg, still more preferably at least about 14,000 U / kg, even more preferably at least about15,000 U / kg, yet more preferably at least about 16,000 U / kg and most preferably at least about16,600 U / kg, wherein the enzyme units are provided as RNase activity, wherein the dosage is providedthrough the feed additive, feed supplement, or animal feed composition comprising the feed additive or the feed supplement.Clause 234. The feed additive or the feed supplement or the animal feed composition for use of any one of clauses 210 to 233, wherein the at least one nuclease is administered at a dosage ranging from about 100 to about 50,000 U / kg of animal feed, from about 200 to about 40,000 U / kg, more preferably about 300 to about 30,000 U / kg, still more preferably about 390 to about 20,000 U / kg, still more preferably about 390 to about 15,000 U / kg, even more preferably about 390 to about 14,000 U / kg, yet more preferably about 390 to about 12,000 U / kg, and particularly preferably at a final concentration ranging from about 390 to about 11,880 U / kg, wherein the enzyme units are provided as DNase activity, wherein the dosage is provided through the feed additive, feed supplement, or animal feed composition comprising the feed additive or the feed supplement.Clause 235. The feed additive or the feed supplement or the animal feed composition for use of any one of clauses 210 to 234, wherein the at least one nuclease is administered at a dosage ranging from about 1,000 to about 50,000 U / kg of animal feed, from about 2,000 to about 40,000 U / kg, more preferably about 3,000 to about 30,000 U / kg, still more preferably about 4,000 to about 20,000 U / kg, still more preferably about 5,000 to about 18,000 U / kg and particularly preferably at a final concentration ranging from about 6,400 to about 16,687 U / kg, wherein the enzyme units are provided as RNase activity, wherein the dosage is provided through the feed additive, feed supplement, or animal feed composition comprising the feed additive or the feed supplement.Clause 236. The feed additive or the feed supplement or the animal feed composition for use of any one of clauses 210 to 235, wherein the treatment or amelioration of subacute necrotic enteritis is measured in terms of at least one of the following parameters: improved feed conversion ratio (FCR), improved body weight adjusted feed conversion ratio (bwFCR), improved growth rate, improved body weight gain (BWG), improved European Production Efficiency Factor (EPEF), reduced mortality rate, improved nutrient retention (NR) such as metabolizable energy and / or nitrogen, reduced intestinal lesion score, improved villi height (VH), improved villi width (VW), improved crypt depth (CD), improved VH:CD ratio (VCR), improved villi surface area and / or presence of pathogenic microorganisms / organisms within the digestive system.Clause 237. The feed additive or the feed supplement or the animal feed composition for use of any one of clauses 210 to 236, wherein a clinical or subclinical intestinal disease challenge is present in the animal.Clause 238. The feed additive or the feed supplement or the animal feed composition for use of clause 237, wherein the clinical or subclinical intestinal disease challenge may be caused by a pathogenic bacterium.Clause 239. The feed additive or the feed supplement or the animal feed composition for use of any one of clauses 237 to 238, wherein the pathogenic bacterium is Clostridium perfringens.Clause 240. The feed additive or the feed supplement or the animal feed composition for use of any one of clauses 237 to 239, wherein the clinical or subclinical intestinal disease challenge includes additionally a challenge with Eimeria species.Clause 241. The feed additive or the feed supplement or the animal feed composition for use of any one of clauses 210 to 240, wherein the feed additive or feed supplement or feed composition further comprises a suitable carrier.Clause 242. The feed additive or the feed supplement or the animal feed composition for use of any one of clauses 210 to 241, wherein the feed additive or feed supplement or feed composition further comprises at least one feed additive, wherein the at least one further feed additive is an enzyme selected from the group of phytases, carbohydrases, and proteases.Clause 243. The feed additive or the feed supplement or the animal feed composition for use of any one of clauses 210 to 242, wherein the animal is a monogastric animal or a ruminant animal.Clause 244. The feed additive or the feed supplement or the animal feed composition for use according to clause 243, wherein the monogastric animal is selected from the group consisting of birds, swine, dogs, cats, fish, shellfish, humans, primates, calves, and horses.Clause 245. The feed additive or the feed supplement or the animal feed composition for use according to clause 243, wherein the ruminant animal is selected from the group consisting of bovine, sheep, goat, camel, deer, llama, antelope, alpaca, and wildebeest.Clause 246. A kit for optimizing the nutritional value of an animal diet or animal feed, comprising: (a) at least one nuclease; and (b) instructions to enable supplementation of the animal diet or the animal feed with the at least one nuclease.

[0308] All references cited herein are hereby incorporated by reference in their entireties, whether previously specifically incorporated or not.

[0309] Having now fully described the disclosure, it will be appreciated by those skilled in the art that the same can be performed within a wide range of equivalent parameters, concentrations, and conditions without departing from the spirit and scope of the disclosure and without undue experimentation. While this disclosure has been described in connection with specific embodiments thereof, it will be understood that it is capable of further modifications. This application is intended to cover any variations, uses, or adaptations of the disclosure following, in general, the principles of the disclosure and including such departures from the present disclosure as come within known or customary practice within the art to which the disclosure pertains and may be applied to the essential features hereinbefore set forth.

[0310] The following examples further illustrate the invention but are not to be construed as limiting its scope.

[0311] Example 1 : Nuclease activity assay

[0312] The Nuclease Activity Assay is based upon the release of short, acid soluble oligonucleotides (cleaved polynucleotides or oligonucleotides) from DNA or RNA substrate (polynucleotide substrate) which leads to an increase in absorbance at 260 nm.

[0313] The endonucleases from Serratia marcescens (SEQ ID NO:2; commercially available as NuCLEANase, c-LEcta GmbH, Germany) and from Penicillium citrinum (ribonuclease P, commercially available as Nuclease RP-1G; Amano Enzymes, Japan) referred to as Nuclease 1 and Nuclease 2 respectively, were provided in lyophilized form. Nuclease activity was measured according to the following protocol as DNase- and RNase activity, using DNA- and RNA- substrates, respectively.

[0314] Substrate buffer used for DNase activity determination: 50 mM Tris-HCl pH 8.0, 1 mM MgC12, 0.1 mg / ml BSA, 1 mg / ml DNA (salmon testes).

[0315] Substrate buffer used for RNase activity determination: 50 mM Tris-HCl pH 8.0, 1 mM MgC12, 0.1 mg / mL BSA, 1 mg / mL RNA (baker's yeast).

[0316] The lyophilized nucleases were diluted prior to use in 50 mM Tris-HCl pH 8.0, 1 mM MgC12, 0.1 mg / mL BSA to obtain values within the linear range of the assay. Typically, values within the linear range are obtained for samples with 200-300 U / pl with a dilution of 1: 30,000 and for samples with 300-400 U / pL with a dilution of 1: 40,000.

[0317] After equilibration of substrate buffer at 37 °C, the reaction was started by adding 125 pl diluted nucleases or “buffer blank” (50 mM Tris-HCl pH 8.0, 1 mM MgC12, 0.1 mg / ml BSA) to 2.5 ml substrate buffer followed by incubation at 37 °C. 500 pl samples are drawn after exactly 15, 30, 45 and 60 min and immediately inactivated by adding 500 pl of 4 % perchloric acid. Acidified mixtures were incubated on ice for at least 45 minutes and centrifuged subsequently (10 min at ~ 17,000 x g). The amount of acid soluble nucleotides in the supernatant was measured at 260 nm.

[0318] The activity of the enzyme is specified in Units. One Unit is defined as the amount of enzyme that causes a change in absorbance at 260 nm of 1.0 Absorbance Unit in 30 minutes at pH 8.0 at 37°C. Nuclease activities are given in Units per gram of the lysate in Table 2. Nuclease 1 was lyophilized in two different concentrations according to Table 2.Table 2 DNase and RNase activities measured for Nuclease 1 and Nuclease 2

[0319] Example 2: Nucleases in feed on broiler chickens - study design

[0320] The effect of the invention object of this document on indicators of growth performance and health was evaluated in broilers under subacute necrotic enteritis (NE) challenge. NE is known to cause damage to the gut of broilers, the severity of which is associated with the strength of the disease. Although acute necrotic enteritis outbreaks can be observed in commercial poultry production, subacute models seek simulate conditions typical of commercial production more closely than acute challenge studies, as it can be assumed that some level of subacute necrotic enteritis is present in most commercial flocks, which may be hindering growth performance and causing losses of integrity and functionality at gut level.

[0321] A total of 3,900 Cobb 500 broilers were raised in floor pens. All birds were spray-vaccinated with coccidia vaccine (Coccivac B-52) with the label recommended dosage on day of hatch. Birds received feed ad-libitum appropriate to the treatment using diet compositions according to Table 3. A change in diet composition from starter to grower diet occurred on day 21. On day 35 the grower diet was replaced with the finisher diet. The birds were allocated to one of six dietary treatments according to Table 4 with 13 replicates per treatment.Table 3: Ingredient and chemical composition of the feed given to broiler chickens from 0 to 42 days of age0322] The nuclease activity (DNase and RNase activity) of the two different nucleases, Nuclease 1 and Nuclease 2, was determined as described in Example 1. For the treatment with Nuclease 1, two different concentrations and dosages were applied according to Table 2 and Table 4. The groups were subjected to a sub-clinical NE challenge with Clostridium perfringens on day 19, 20 and 21 of age. The titration levels were approximately 1.0 x 108'9cfu / bird of Clostridium perfringens, isolated from the field and known to cause NE. Each pen received the same amount of inoculum. The inoculum was administered by mixing into the feed in the base of the tube feeders. The birds had continuous access to feed and water throughout the trial and ambient temperature was maintained in accordance with breeder guidelines. Pen weight and feed consumption were recorded on day 0, 21 and 35 of age. On day 21, 3 birds per pen were sacrificed to assess ileal histopathology and NE lesion scores. On day 21, fresh faeces were collected to estimate faecal oocyst excretion (OPG) for different types of Eimeria spp, as well as total.Table 4 Experimental Design and Treatment Groups1BMD, Bacitracin methylene disalicylate; given as dose of gram per short ton (US ton)

[0323] Example 3 : Animal growth performance

[0324] Animal growth performance indicators were measured on days 21 (NE lesion scores and total OPG) and 35 (body weight, feed intake, body weight gain, EPEF, FCR, bwFCR and mortality) for the study groups as described in Example 2 and are provided in Table 4.Table 5 Growth performance of different treatment groups in broiler chickensa,bmeans within a column not sharing common superscripts are significantly different (P< 0.05)1Average daily gain from day 0 to 352European production efficiency factor3Mortality adjusted4Mortality due to necrotic enteritis5Oocyst excretion per gram of faeces6BMD, Bacitracin methylene disalicylate (50 g / ton)

[0325] The above data in Table 5 demonstrate that the treatment with a nuclease through feed is able to improve the animal growth performance in animals under a subacute necrotic enteritis challenge compared to the unmedicated control group. Specifically, for the nuclease treatment groups, body weights, FCR, bwFCR, EPEF, mortality, NE lesion scores and OPG were improved compared to the unmedicated control. When FCR was adjusted to assume an equal body weight of 1.60kg, these differences became significant, showing a significant reduction in body weight adjusted FCR compared to the unmedicated control. Similarly, there were significant reductions in NE associated mortality for the nuclease treatment groups compared to the unmedicated control group. The lowest mortality was observed for treatment Group 3. NE lesion scores were reduced for all nuclease groups compared to the unmedicated control. A significant reduction was observed in the treatment Groups 3 and 4 (different concentrations of Nuclease 1) compared to the unmedicated control. OPG counts were also reduced in all nuclease treatment groups compared to the unmedicated control. For the parameters EPEF, FCR, bwFCR, mortality and NE lesion score, nuclease treated animals presented an improvement even compared to the antibiotic control (Group 2) and to the group treated with the nucleotide enriched yeast extract (Group 6).

[0326] Example 4: Animal gut integrity

[0327] Animal gut integrity was measured on day 21 for all study groups as described in Example 2 upon histopathological evaluation and corresponding data are provided in Table 6. Due to the relatively low number of replicates for histopathology measurements (3 birds per pen), all nuclease treatments were grouped together to improve reliability of the effects of nuclease on intestinal damage. The nuclease treatment groups showed the highest VCR compared to the unmedicated control (Group 2) and to the group treated with the nucleotide enriched yeast extract (Group 6).Table 6 Gut integrity of different treatment groups in broiler chickens1Villus height to crypt depth ratio2Bacitracin methylene disalicylate (50 g / ton)

Claims

Patent claims:

1. A method for improving an animal growth performance and / or nutrient utilization, comprising administering to an animal at least one nuclease, wherein the at least one nuclease is administered by means of a feed additive or feed supplement or by an animal feed composition comprising the feed additive or the feed supplement.

2. A method for improving an animal growth performance, comprising administering to an animal at least one nuclease, wherein the at least one nuclease is administered by means of a feed additive or feed supplement or by an animal feed composition comprising the feed additive or the feed supplement.

3. A method for improving nutrient utilization in an animal, comprising administering to an animal at least one nuclease, wherein the at least one nuclease is administered by means of a feed additive or feed supplement or by an animal feed composition comprising the feed additive or the feed supplement.

4. A method for improving gut integrity and homeostasis of an animal, comprising administering to the animal at least one nuclease, wherein the at least one nuclease is administered by means of a feed additive or feed supplement and / or by an animal feed composition.

5. A method for improving gut integrity of an animal, comprising administering to the animal at least one nuclease, wherein the at least one nuclease is administered by means of a feed additive or feed supplement or by an animal feed composition comprising the feed additive or the feed supplement.

6. A method for treatment or amelioration of subacute necrotic enteritis in an animal, comprising administering to the animal at least one nuclease, wherein the at least one nuclease is administered by means of a feed additive or feed supplement or by an animal feed composition comprising the feed additive or the feed supplement.

7. The method according to any one of claims 1 or 6, wherein the at least one nuclease is selected from the group consisting of endonucleases, exonucleases, and mixed exo- / endonucleases, preferably selected from endonucleases.

8. The method according to any one of the preceding claims, wherein the at least one nuclease has a DNA-degrading activity, an RNA-degrading activity, or a mixed DNA and RNA degrading activity.

9. The method according to any one of the preceding claims, wherein the at least one nuclease is selected from the group of enzymes classified under EC classes selected from EC3.1.11, EC3.1.13, EC3.1.14, EC3.1.21, EC3.1.25, EC 3.1.26, EC3.1.27, EC 3.1.30 and EC 3.1.31.

10. The method according to any one of the preceding claims, wherein the at least one nuclease is selected from the group of enzymes classified under EC classes selected from EC 3.1.26, EC 3.1.30 and EC 3.1.31.

11. The method according to any one of the preceding claims, wherein the at least one nuclease is selected from the group of enzymes classified under EC classes selected from EC 3.1.26 and EC 3.1.30.

12. The method according to claim 9, wherein the at least one nuclease is selected from the group of enzymes classified under EC classes selected from EC 3.1.11.2, EC 3.1.11.5, EC 3.1.11.6, EC 3.1.13.4, EC 3.1.14.1, EC 3.1.21.1, EC 3.1.21.2, EC 3.1.21.3, EC 3.1.21.4, EC 3.1.21.6, EC 3.1.25.1, EC 3.1.26.3, EC 3.1.26.4, EC 3.1.26.5, EC 3.1.26.8, EC 3.1.26.9, EC 3.1.26.11, EC 3.1.27.1, EC 3.1.27.3, EC 3.1.27.5, EC 3.1.30.1, EC 3.1.30.2 and EC 3.1.31.1.

13. The method according to claim 12, wherein the at least one nuclease is selected from the group of enzymes classified under EC classes selected from EC 3.1.26.5 and EC 3.1.30.2.

14. The method according to any one of the preceding claims, wherein the at least one nuclease is derived from a microbial origin.

15. The method according to any one of the preceding claims, wherein the at least one nuclease is derived from a gram-negative bacterium, preferably selected from the group consisting of Acidithiobacillales, Aeromonadales, Alteromonadales, Cardiobacteriales, Chromatiales, Enterobacterales, Legionellales, Methylococcales, Oceanospirillales, Pasteurellales, Pseudomonadales, Thiotrichales, Vibrionales and Xanthomonadales, more preferably from Enterobacterales.

16. The method according to any one of the preceding claims, wherein the at least one nuclease is derived from a genus of the order Enterobacterales, selected from the group consisting of Arsenophonus, Brenneria, Buchnera, Budvicia, Buttiauxella, Cedecea, Citrobacter, Dickeya, Edwardsiella, Enterobacter, Erwinia, Escherichia, Ewingella, Elafnia, Klebsiella, Kluyvera, Leclercia, Leminorella, Moellerella, Marganella, Obesumbacterium, Pantoea, Pectobacterium, Photorhabdus, Plesiomonas, Pragia, Proteus, Providencia, Rahnella, Raoultella, Saccharobacter, Salmonella, Samsonia, Serratia, Shigella, Sodalis, Tatumella, Thorsellia, Trabulsiella, Wigglesworthia, Xenorhabdus, Yersinia and Yokenella, preferably from Serratia.

17. The method according to any of the preceding claims, wherein the at least one nuclease is derived from a species of the genus Serratia selected from the group consisting of Serratia entomophila, Serratia ficaria, Serratia fonticola, Serratia grimesii, Serratia marcescens, Serratia liquefaciens, Serratia odorifera, Serratia plymuthica, Serratia proteamaculans, Serratia quinivorans, Serratia rubidaea and Serratia ureilytica,18. The method according to any of the preceding claims, wherein the at least one nuclease is derived from Serratia marcescens.

19. The method according to any one of the preceding claims, wherein the at least one nuclease is at least 70%, preferably at least 75%, more preferably at least 80%, even more preferably at least 85%, still more preferably at least 90%, still more preferably at least 95%, still more preferablyat least 98%, most preferably at least 99%, or in particular at least 100% identical to the sequence of SEQ ID NO: 1 or SEQ ID NO:2.

20. The method according to any one of claims 1 to 14, wherein the at least one nuclease is derived from a fungus selected from the group consisting of Penicillium, Candida, Saccharomyces, and Trichoderma, preferably from Penicillium.

21. The method according to claim 20, wherein the at least one nuclease is derived from the fungus Penicillium citrinum.

22. The method according to any one of the preceding claims, wherein the at least one nuclease is a recombinant protein.

23. The method according to any one of the preceding claims, wherein the at least one nuclease is a functional variant that retains nuclease activity of the reference nuclease.

24. The method according to claim 23, wherein the functional variant of the nuclease exhibits an improved specific nuclease activity compared to the reference nuclease, as measured under standard test conditions, preferably with the improvement being at least 5%, preferably at least 10%, more preferably at least 20%, even more preferably at least 100%.

25. The method according to claim 23 or 24, wherein the functional variant of the nuclease exhibits an improved thermal stability compared to the reference nuclease, as measured under standard test conditions, preferably with the improvement being at least 5%, preferably at least 10%, more preferably at least 20%, even more preferably at least 100%.

26. The method according to any one of the preceding claims, wherein the at least one nuclease is produced by a fermentation process using a bacterial host cell, preferably selected from Escherichia coli, Bacillus subtilis and Bacillus amyloliquefaciens.

27. The method according to any one of the preceding claims, wherein the at least one nuclease is administered at a dosage of at least about 100 U / kg of animal feed, preferably at least about 200 U / kg, more preferably at least about 400 U / kg, still more preferably at least about 800 U / kg, still more preferably at least about 1,200 U / kg, still more preferably at least about 1,500 U / kg, still more preferably at least about 2,000 U / kg of animal feed, still more preferably at least about 3,000 U / kg, still more preferably at least about 3,500 U / kg, still more preferably at least about 4,000 U / kg, still more preferably at least about 5,000 U / kg, still more preferably at least about 6,000 U / kg, still more preferably at least about 7,000 U / kg, still more preferably at least about 8,000 U / kg, still more preferably at least about 9,000 U / kg, even more preferably at least about 10,000 U / kg, yet more preferably at least about 11,000 U / kg and most preferably at least about 12,000 U / kg, wherein the enzyme units are provided as DNase activity, wherein the dosage is provided through the feed additive, feed supplement, or animal feed composition comprising the feed additive or the feed supplement.

28. The method according to claim 27, wherein the at least one nuclease is administered at a dosage ranging from about 100 to about 50,000 U / kg of animal feed, from about 200 to about40,000 U / kg, more preferably about 300 to about 30,000 U / kg, still more preferably about 390 to about 20,000 U / kg, still more preferably about 390 to about 15,000 U / kg, even more preferably about 390 to about 14,000 U / kg, yet more preferably about 390 to about 12,000 U / kg, and particularly preferably at a final concentration ranging from about 390 to about 11,880 U / kg, wherein the enzyme units are provided as DNase activity, wherein the dosage is provided through the feed additive, feed supplement, or animal feed composition comprising the feed additive or the feed supplement.

29. The method according to any one of the preceding claims, wherein the at least one nuclease is administered at a dosage of at least about 1,000 U / kg of animal feed, preferably at least about 2,000 U / kg, more preferably at least about 5,000 U / kg, still more preferably at least about 6,000 U / kg, still more preferably at least about 7,000 U / kg, still more preferably at least about 8,000 U / kg, still more preferably at least about 9,000 U / kg, still more preferably at least about 10,000 U / kg, still more preferably at least about 11,000 U / kg, still more preferably at least about 12,000 U / kg, still more preferably at least about 13,000 U / kg, still more preferably at least about 14,000 U / kg, even more preferably at least about 15,000 U / kg, yet more preferably at least about 16,000 U / kg and most preferably at least about 16,600 U / kg, wherein the enzyme units are provided as RNase activity, wherein the dosage is provided through the feed additive, feed supplement, or animal feed composition comprising the feed additive or the feed supplement.

30. The method according to claim 29, wherein the at least one nuclease is administered at a dosage ranging from about 1,000 to about 50,000 U / kg of animal feed, from about 2,000 to about 40,000 U / kg, more preferably about 3,000 to about 30,000 U / kg, still more preferably about 4,000 to about 20,000 U / kg, still more preferably about 5,000 to about 18,000 U / kg and particularly preferably at a final concentration ranging from about 6,400 to about 16,687 U / kg, wherein the enzyme units are provided as RNase activity, wherein the dosage is provided through the feed additive, feed supplement, or animal feed composition comprising the feed additive or the feed supplement.

31. The method according to any one of the preceding claims, wherein a clinical or subclinical intestinal disease challenge is present in the animal.

32. The method according to claim 31 , wherein the clinical or subclinical intestinal disease challenge may be caused by a pathogenic bacterium.

33. The method according to claim 32, wherein the pathogenic bacterium is Clostridium perfringens.

34. The method according to any one of claims 31 to 33, wherein the clinical or subclinical intestinal disease challenge includes additionally a challenge with Eimeria species.

35. The method according to any one of the preceding claims, wherein the feed additive or feed supplement or feed composition further comprises a suitable carrier.

36. The method according to any one of the preceding claims, wherein the feed additive or feed supplement or feed composition further comprises at least one further feed additive, wherein theat least one further feed additive is an enzyme selected from the group of phytases, carbohydrases, and proteases.

37. The method according to any of the preceding claims, wherein the animal is a monogastric animal or a ruminant animal.

38. The method according to claim 37, wherein the monogastric animal is selected from the group consisting of birds, swine, dogs, cats, fish, shellfish, humans, primates, calves, and horses.

39. The method according to claim 37, wherein the ruminant animal is selected from the group consisting of bovine, sheep, goat, camel, deer, llama, antelope, alpaca, and wildebeest.

40. The method according to any one of claim 1, 2 and 7 to 39, wherein the improved animal growth performance is measured in terms of at least one of the following parameters: improved feed conversion ratio (FCR), improved body weight adjusted feed conversion ratio (bwFCR), improved growth rate, improved body weight gain (BWG), improved European Production Efficiency Factor (EPEF), and / or reduced mortality.

41. The method according to any one of claims 1, 3 and 7 to 39, wherein the improved nutrient utilization or nutrient digestibility is measured in terms of at least one of the following parameters: nutrient retention (NR), metabolizable energy digestibility, nitrogen-corrected apparent metabolizable energy (AMEn), and / or crude protein digestibility.

42. The method according to any of claims 4, 5 and 7 to 39, wherein the improved gut integrity is measured in terms of at least one of the following parameters: villi height (VH), crypt depth (CD), villi width (VW), VH:CD ratio (VCR), villi surface area, intestinal lesion score, microbial density and / or presence of pathogenic or non-pathogenic microorganisms / organisms within the digestive system.

43. The method according to any of claims 6 to 39, wherein the treatment or amelioration of subacute necrotic enteritis is measured in terms of at least one of the following parameters: improved feed conversion ratio (FCR), improved body weight adjusted feed conversion ratio (bwFCR), improved growth rate, improved body weight gain (BWG), improved European Production Efficiency Factor (EPEF), reduced mortality rate, improved nutrient retention (NR) such as metabolizable energy and / or nitrogen, reduced intestinal lesion score, improved villi height (VH), improved villi width (VW), improved crypt depth (CD), improved VH:CD ratio (VCR), improved villi surface area and / or presence of pathogenic microorganisms / organisms within the digestive system.

44. A feed additive or feed supplement comprising at least one nuclease.

45. The feed additive or feed supplement according to claim 44, wherein the at least one nuclease is selected from the group consisting of endonucleases, exonucleases, and mixed exo- / endonucleases, preferably selected from endonucleases.

46. The feed additive or feed supplement according to claim 44 or 45, wherein the at least one nuclease has a DNA-degrading activity, an RNA-degrading activity, or a mixed DNA and RNA degrading activity.

47. The feed additive or feed supplement according to any one of claims 44 to 46, wherein the at least one nuclease is selected from the group of enzymes classified under EC classes selected from EC3.1.11, EC3.1.13, EC3.1.14, EC3.1.21, EC3.1.25, EC 3.1.26, EC3.1.27, EC 3.1.30 and EC 3.1.31.

48. The feed additive or feed supplement according to claim 47, wherein the at least one nuclease is selected from the group of enzymes classified under EC classes selected from EC 3.1.26, EC 3.1.30 and EC 3.1.31.

49. The feed additive or feed supplement according to claim 48, wherein the at least one nuclease is selected from the group of enzymes classified under EC classes selected from EC 3.1.26 and EC 3.1.30.

50. The feed additive or feed supplement according to claim 47, wherein the at least one nuclease is selected from the group of enzymes classified under EC classes selected from EC 3.1.11.2, EC 3.1.11.5, EC 3.1.11.6, EC 3.1.13.4, EC 3.1.14.1, EC 3.1.21.1, EC 3.1.21.2, EC 3.1.21.3, EC 3.1.21.4, EC 3.1.21.6, EC 3.1.25.1, EC 3.1.26.3, EC 3.1.26.4, EC 3.1.26.5, EC 3.1.26.8, EC 3.1.26.9, EC 3.1.26.11, EC 3.1.27.1, EC 3.1.27.3, EC 3.1.27.5, EC 3.1.30.1, EC 3.1.30.2 and EC 3.1.31.1.

51. The feed additive or feed supplement according to claim 50, wherein the at least one nuclease is selected from the group of enzymes classified under EC classes selected from EC 3.1.26.5 and EC 3.1.30.2.

52. The feed additive or feed supplement according to any one of claims 44 to 51, wherein the at least one nuclease is derived from a microbial origin.

53. The feed additive or feed supplement according to any one of claims 44 to 52, wherein the at least one nuclease is derived from a gram-negative bacterium, preferably selected from the group consisting of Acidithiobacillales, Alteromonadales, Cardiobacteriales, Chromatiales, Enterobacterales, Legionellales, Methylococcales, Oceanospirillales, Pasteurellales, Pseudomonadales, Thiotrichales, Vibrionales and Xanthomonadales, more preferably from Enterobacterales.

54. The feed additive or feed supplement according to any one of claims 44 to 53, wherein the at least one nuclease is derived from a genus of the order Enterobacterales selected from the group consisting of Arsenophonus, Brenneria, Buchnera, Budvicia, Buttiauxella, Cedecea, Citrobacter, Dickeya, Edwardsiella, Enterobacter, Erwinia, Escherichia, Ewingella, Elafnia, Klebsiella, Kluyvera, Leclercia, Leminorella, Moellerella, Marganella, Obesumbacterium, Pantoea, P ectobacterium, Photorhabdus, Plesiomonas, Pragia, Proteus, Providencia, Rahnella, Raoultella, Saccharobacter, Salmonella, Samsonia, Serratia, Shigella, Sodalis, Tatumella,Thorsellia, Trabulsiella, Wiggle sworthia, Xenorhabdus, Yersinia and Yokenella, preferably from Serratia.

55. The feed additive or feed supplement according to any one of claims 44 to 54, wherein the at least one nuclease is derived from a species of the genus Serratia selected from the group consisting of Serratia entomophila, Serratia ficaria, Serratia fonticola, Serratia grimesii, Serratia marcescens, Serratia liquefaciens, Serratia odorifera, Serratia plymuthica, Serratia proteamaculans, Serratia quinivorans, Serratia rubidaea and Serratia ureilytica,56. The feed additive or feed supplement according to any one of claims 44 to 55, wherein the at least one nuclease is derived from Serratia marcescens.

57. The feed additive or feed supplement according to any one of claims 44 to 56, wherein the at least one nuclease is at least 70%, preferably at least 75%, more preferably at least 80%, even more preferably at least 85%, still more preferably at least 90%, still more preferably at least 95%, still more preferably at least 98%, most preferably at least 99%, or in particular at least 100% identical to the sequence of SEQ ID NO: 1 or SEQ ID NO:2.

58. The feed additive or feed supplement according to any one of claims 44 to 52, wherein the at least one nuclease is derived from a fungus selected from the group consisting of Penicillium, Candida, Saccharomyces, and Trichoderma, preferably from Penicillium.

59. The feed additive or feed supplement according to claim 58, wherein the at least one nuclease is derived from the fungus Penicillium citrinum.

60. The feed additive or feed supplement according to any one of claims 44 to 59, wherein the at least one nuclease is a recombinant protein.

61. The feed additive or feed supplement according to any one of claims 44 to 60 wherein the at least one nuclease is a functional variant that retains nuclease activity of the reference nuclease.

62. The feed additive or feed supplement according to claim 61, wherein the functional variant of the nuclease exhibits an improved specific nuclease activity compared to the reference nuclease, as measured under standard test conditions, preferably with the improvement being at least 5%, preferably at least 10%, more preferably at least 20%, even more preferably at least 100%.

63. The feed additive or feed supplement according to claim 61 or 62, wherein the functional variant of the nuclease exhibits an improved thermal stability compared to the reference nuclease, as measured under standard test conditions, preferably with the improvement being at least 5%, preferably at least 10%, more preferably at least 20%, even more preferably at least 100%.

64. The feed additive or feed supplement according to any one of claims 44 to 63, wherein the at least one nuclease is produced by a fermentation process using a bacterial host cell, preferably selected from Escherichia coli, Bacillus subtilis and Bacillus amyloliquefaciens.

65. The feed additive or feed supplement according to any one of claims 44 to 64, wherein the feed additive or feed supplement further comprises a suitable carrier.

66. The feed additive or feed supplement according to any one of claims 44 to 65, wherein the feed additive or feed supplement further comprises at least one further feed additive, wherein the at least one further feed additive is an enzyme selected from the group of phytases, carbohydrases, and proteases.

67. An animal feed composition comprising the feed additive or feed supplement of any one of claims 44 to 66.

68. The animal feed composition according to claim 67, wherein the at least one nuclease is added to the animal feed composition at a concentration of at least about 100 U / kg of animal feed, preferably at least about 200 U / kg, more preferably at least about 400 U / kg, still more preferably at least about 800 U / kg, still more preferably at least about 1,200 U / kg, still more preferably at least about 1,500 U / kg, still more preferably at least about 2,000 U / kg of animal feed, still more preferably at least about 3,000 U / kg, still more preferably at least about 3,500 U / kg, still more preferably at least about 4,000 U / kg, still more preferably at least about 5,000 U / kg, still more preferably at least about 6,000 U / kg, still more preferably at least about 7,000 U / kg, still more preferably at least about 8,000 U / kg, still more preferably at least about 9,000 U / kg, even more preferably at least about 10,000 U / kg, yet more preferably at least about 11,000 U / kg and most preferably at least about 12,000 U / kg, wherein the enzyme units are provided as DNase activity.

69. The animal feed composition according to claim 68, wherein the at least one nuclease is added at a concentration ranging from about 100 to about 50,000 U / kg of animal feed, from about 200 to about 40,000 U / kg, more preferably about 300 to about 30,000 U / kg, still more preferably about 390 to about 20,000 U / kg, still more preferably about 390 to about 15,000 U / kg, even more preferably about 390 to about 14,000 U / kg, yet more preferably about 390 to about 12,000 U / kg, and particularly preferably at a final concentration ranging from about 390 to about 11,880 U / kg, wherein the enzyme units are provided as DNase activity.

70. The animal feed composition according to claim 67 or 68, wherein the at least one nuclease is added at a concentration of at least about 1,000 U / kg of animal feed, preferably at least about 2,000 U / kg, more preferably at least about 5,000 U / kg, still more preferably at least about 6,000 U / kg, still more preferably at least about 7,000 U / kg, still more preferably at least about 8,000 U / kg, still more preferably at least about 9,000 U / kg, still more preferably at least about 10,000 U / kg, still more preferably at least about 11,000 U / kg, still more preferably at least about 12,000 U / kg, still more preferably at least about 13,000 U / kg, still more preferably at least about 14,000 U / kg, even more preferably at least about 15,000 U / kg, yet more preferably at least about 16,000 U / kg and most preferably at least about 16,600 U / kg, wherein the enzyme units are provided as RNase activity.

71. The animal feed composition according to claim 70, wherein the at least one nuclease is added at a concentration ranging from about 1,000 to about 50,000 U / kg of animal feed, from about 2,000 to about 40,000 U / kg, more preferably about 3,000 to about 30,000 U / kg, still morepreferably about 4,000 to about 20,000 U / kg, still more preferably about 5,000 to about 18,000 U / kg and particularly preferably at a final concentration ranging from about 6,400 to about 16,687 U / kg, wherein the enzyme units are provided as RNase activity.

72. Use of a feed additive or feed supplement or feed composition according to any of claims 44 to 71, for improving an animal growth performance, nutrient utilization, gut integrity, and / or treatment or amelioration of necrotic enteritis.

73. The use according to claim 72, wherein the animal is a monogastric or a ruminant animal.

74. The use according to claim 73, wherein the monogastric animal is selected from the group consisting of poultry, birds, swine, dogs, cats, fish, shellfish, humans, primates, calves, and horses.

75. The use according to claim 73, wherein the ruminant animal is selected from the group consisting of bovine, sheep, goat, camel, deer, llama, antelope, alpaca, and wildebeest.

76. The use according to any one of claims 72 to 75, wherein the improved animal growth performance is measured in terms of at least one of the following parameters: improved feed conversion ratio (FCR), improved body weight adjusted feed conversion ratio (bwFCR), improved growth rate, improved body weight gain (BWG), improved European Production Efficiency Factor (EPEF), and / or reduced mortality.

77. The use according to any one of claims 72 to 75, wherein the improved nutrient utilization or nutrient digestibility is measured in terms of at least one of the following parameters: nutrient retention (NR), metabolizable energy digestibility, nitrogen-corrected apparent metabolizable energy (AMEn), and / or crude protein digestibility.

78. The use according to any one of claims 72 to 75, wherein the improved gut integrity is measured in terms of at least one of the following parameters: villi height (VH), crypt depth (CD), villi width (VW), VH:CD ratio (VCR), villi surface area, intestinal lesion score, microbial density and / or presence of pathogenic or non-pathogenic microorganisms / organisms within the digestive system.

79. The use according to any one of claims 72 to 75, wherein the treatment or amelioration of subacute necrotic enteritis is measured in terms of at least one of the following parameters: improved feed conversion ratio (FCR), improved body weight adjusted feed conversion ratio (bwFCR), improved growth rate, improved body weight gain (BWG), improved European Production Efficiency Factor (EPEF), reduced mortality rate, improved nutrient retention (NR) such as metabolizable energy and / or nitrogen, reduced intestinal lesion score, improved villi height (VH), improved villi width (VW), improved crypt depth (CD), improved VH:CD ratio (VCR), improved villi surface area and / or presence of pathogenic microorganisms / organisms within the digestive system.

80. A kit for optimizing the nutritional value of an animal diet or animal feed, comprising: (a) at least one nuclease; and (b) instructions to enable supplementation of the animal diet or the animal feed with the at least one nuclease.