Mixtures comprising RNA and fungicides to control phytopathogenic fungi

Abstract

The present invention relates to mixtures comprising single-stranded (ssRNA) and double-stranded RNA (dsRNA) and fungicides, compositions comprising these mixtures and methods for the control of phytopathogenic fungi of the genus Erysiphe or Botrytis using these mixtures or compositions. The invention relates further to methods to protect plants producing one or more of these single-stranded or double-stranded RNAs against phytopathogenic fungi of the genus Erysiphe or Botrytis by the application of fungicides.

Description

[0001] Mixtures comprising RNA and fungicides to control phytopathogenic fungi.

[0002] Field of the Invention:

[0003] The present invention relates to mixtures comprising single-stranded (ssRNA) and doublestranded RNA (dsRNA) and fungicides, compositions comprising these mixtures and methods for the control of phytopathogenic fungi of the genus Erysiphe or Botrytis using these mixtures or compositions. The invention relates further to methods to protect plants producing one or more of these single-stranded or double-stranded RNAs against phytopathogenic fungi of the genus Erysiphe or Botrytis by the application of fungicides.

[0004] Background of the Invention:

[0005] Plant diseases caused by phytopathogenic fungi are a serious risk in the culturing of plants. Thus, there is a constant need to develop a broad toolkit of fungicides to protect plants and to improve on the shortcomings of existing pesticides. One interest is to develop pesticides based on natural compounds with a sufficiently high performance to replace fungicides based on synthetic compounds. One approach is to take advantage of biological mechanisms in the plant host and / or the fungal pathogen. One of these naturally mechanisms is called RNAi. RNAi generally suppresses gene expression via small RNAs (sRNAs), including microRNAs (miRNAs) and small interfering RNAs (siRNAs). These small RNAs of about 18 to 21 nucleotides are generated by Dicer or Dicer-like (DCL) proteins and loaded into Argonaute (AGO) proteins and silence genes with complementary sequences to the sRNA to control physiological or developmental processes In plants, RNAi plays a critical role in the regulation of gene expression in response to infection by fungal pathogens.

[0006] It has been found that small RNAs are also transported between a plant host and the attacking fungus and vice-versa. This mechanism is employed by an approach called host-induced gene silencing (HIGS). HIGS uses plants which have been genetically engineered to express RNAs with complementary sequences to genes of the phytopathogenic fungi. These small RNAs are then transported into the fungus via RNA trafficking, where they target and silence fungal genes.

[0007] Additionally, it has been found that phytopathogenic fungi can take up small RNA molecules from their environment and that these small RNAs can induce silencing of fungal genes if they have complementary sequences to genes of the fungi. This discovery prompted the development of spray-induced gene silencing (SIGS), in which artificially synthesized small RNAs are sprayed directly onto the fungus or its environment, e.g. the plant parts in risk of infection or already infected, to induce silencing of genes of the attacking fungus.

[0008] In case the right genes are targeted in the fungus, HIGS as well as SIGS can cause mortality, suppression of growth, a decrease in virulence or pathogenicity, or a decrease in propagation / reproductive capacity of the phytopathogenic fungus. One of the target genes, which have been employed in HIGS and SIGS strategies are cytochrome P450 lanosterol C-14 alpha-demethylase (CYP51) genes of fungi, see e.g. WO2015 / 004174, US2018 / 0320179, WO2022 / 192241 and WO2022 / 225915.

[0009] CYP51 is also a target for synthetic fungicides such as systemic DM Is (demethylation inhibitors), such as tebuconazole, triadimefon, and prochloraz. These DMI fungicides inhibit ergosterol biosynthesis by binding to CYP51 , which results in disturbance of the fungal membrane integrity (Yoshida: Lanosterol 14a-demethylase. In: Schenkman, H., Grein, K. (Eds.), Cytochromes P450. Springer-Verlag, Berlin, 1993. pages 627-639). However, the heavy reliance on DMI fungicides since their discovery in the mid-1970s has led to the emergence of many DMI-resistant phytopathogen strains over the last few years.

[0010] It has now been found that a combination of HIGS or SIGS with chemical or biological fungicides can have more than additional effects for controlling phytopathogenic fungi and can be a means to overcome or delay the emergence of fungicide resistant strains.

[0011] Figures 1 :

[0012] Figure 1 depicts a multiple sequence alignment with the coding region of the Cyp51 genes of Erysiphe necator, Erysiphe cichoracearum, Erysiphe neolycopersici and Botrytis cinerea (SEQ ID Nos: 4, 91, 122 and 60, respectively), as well as transcriptional template regions of RNAs described by SEQ ID Nos: 15, 21 , 34, 274, 276, 24, 27 and 30.

[0013] Description of the invention:

[0014] Definitions:

[0015] Unless otherwise noted, the terms used herein are to be understood according to conventional usage by those of ordinary skill in the relevant art.

[0016] Before describing in detail exemplary embodiments of the present invention, definitions important for understanding the present invention are given. Unless stated otherwise or apparent from the nature of the definition, the definitions apply to all compounds, methods and uses described herein.

[0017] As used in this specification and in the appended claims, the singular forms of "a" and "an" also include the respective plurals unless the context clearly dictates otherwise.

[0018] In the context of the present invention, the terms "about" and "approximately" denote an interval of accuracy that a person skilled in the art will understand to still ensure the technical effect of the feature in question. The term typically indicates a deviation from the indicated numerical value of ±20 %, preferably ±15 %, more preferably ±10 %, and even more preferably ±5 %. Furthermore, the terms "first", "second", "third" or "(a)", "(b)", "(c)", "(d)" etc. and the like in the description and in the claims, are used for distinguishing between similar elements and not necessarily for describing a sequential or chronological order. It is to be understood that the terms so used are interchangeable under appropriate circumstances and that the embodiments of the invention described herein are capable of operation in other sequences than described or illustrated herein. In case the terms "first", "second", "third" or "(a)", "(b)", "(c)", "(d)", "i", "ii" etc. relate to steps of a method or use or assay there is no time or time interval coherence between the steps, i.e. the steps may be carried out simultaneously or there may be time intervals of seconds, minutes, hours, days, weeks, months or even years between such steps, unless otherwise indicated in the application as set forth herein above or below.

[0019] Throughout this application, various publications are referenced. The disclosures of all of these publications and those references cited within those publications in their entireties are hereby incorporated by reference into this application in order to more fully describe the state of the art to which this invention pertains.

[0020] It is to be understood that the term "comprising" is not limiting. For the purposes of the present invention the term "consisting of" is considered to be a preferred embodiment of the term "comprising". If hereinafter a group is defined to comprise at least a certain number of embodiments, this is meant to also encompass a group which preferably consists of these embodiments only.

[0021] “Parent” sequence (also called “parent enzyme” or “parent protein”) is the starting sequences for introduction of changes (e.g. by introducing one or more amino acid substitutions) of the sequence resulting in “variants” of the parent sequences. Thus, the term “enzyme variant” or “sequence variant” or “protein variant” are used in reference to parent enzymes that are the origin for the respective variant enzymes. Therefore, parent enzymes include wild type enzymes and variants of wild-type enzymes which are used for development of further variants. Variant enzymes differ from parent enzymes in their amino acid sequence to a certain extent.

[0022] In describing the variants of the present invention, the abbreviations for single amino acids used according to the accepted IIIPAC single letter or three letter amino acid abbreviation is used. “Amino acid alteration” as used herein refers to amino acid substitution, deletion, or insertion. “Substitutions” are described by providing the original amino acid followed by the number of the position within the amino acid sequence, followed by the substituted amino acid. For example, the substitution of histidine at position 120 with alanine is designated as “His120Ala” or “H120A”. Substitutions can also be described by merely naming the resulting amino acid in the variant without specifying the amino acid of the parent at this position, e.g., “X120A” or “120A” or “Xaa120Ala” or“120Ala”.

[0023] “Deletions” are described by providing the original amino acid followed by the number of the position within the amino acid sequence, followed by *. Accordingly, the deletion of glycine at position 150 is designated as “Gly150*” or G150*”. Alternatively, deletions are indicated by e.g. “deletion of D183 and G184”.

[0024] “Insertions” are described by providing the original amino acid followed by the number of the position within the amino acid sequence, followed by the original amino acid and the additional amino acid. For example, an insertion at position 180 of lysine next to glycine is designated as “Gly180GlyLys” or “G180GK”. When more than one amino acid residue is inserted, such as e.g. a Lys and Ala after Gly180 this may be indicated as: Gly180GlyLysAla or G195GKA.

[0025] In cases where a substitution and an insertion occur at the same position, this may be indicated as S99SD+S99A or in short S99AD. In cases where an amino acid residue identical to the existing amino acid residue is inserted, it is clear that degeneracy in the nomenclature arises. If for example a glycine is inserted after the glycine in the above example this would be indicated by G180GG. Variants comprising multiple alterations are separated by “+”, e.g., “Arg170Tyr+Gly195Glu” or “R170Y+G195E” representing a substitution of arginine and glycine at positions 170 and 195 with tyrosine and glutamic acid, respectively. Alternatively, multiple alterations may be separated by space or a comma, e.g., R170Y G195E or R170Y, G195E respectively. Where different alternative alterations can be introduced at a position, the different alterations are separated by a comma, e.g., “Arg170Tyr, Glu” and R170T, E, respectively, represents a substitution of arginine at position 170 with tyrosine or glutamic acid. Alternative substitutions at a particular position can also be indicated as X120A,G,H, 120A,G,H, X120A / G / H, or 120A / G / H. Alternatively, different alterations or optional substitutions may be indicated in brackets, e.g., Arg170[Tyr, Gly] or Arg170{Tyr, Gly} or in short R170 [Y, G] or R170 {Y, G}.

[0026] A "synthetic" or “artificial” compound is produced by in vitro chemical and / or enzymatic synthesis. The term “native” (or naturally occurring or wildtype or endogenous) cell or organism or polynucleotide or polypeptide refers to the cell or organism or polynucleotide or polypeptide as found in nature (i.e., without there being any human intervention). For the purposes of the invention, "recombinant" (or transgenic) with regard to a cell or an organism means that the cell or organism contains a heterologous polynucleotide which is introduced by man by gene technology and with regard to a polynucleotide includes all those constructions brought about by man by gene technology I recombinant DNA techniques in which either

[0027] (a) the sequence of the polynucleotide or a part thereof, or

[0028] (b) one or more genetic control sequences which are operably linked with the polynucleotide, including but not limited thereto a promoter, or

[0029] (c) both a) and b) are not located in their wildtype genetic environment or have been modified by man.

[0030] The term "heterologous” (or exogenous or foreign or recombinant or non-native) polypeptide is defined herein as a polypeptide that is not native to the host cell, a polypeptide native to the host cell in which structural modifications, e.g., deletions, substitutions, and / or insertions, have been made by recombinant DNA techniques to alter the native polypeptide, or a polypeptide native to the host cell whose expression is quantitatively altered or whose expression is directed from a genomic location different from the native host cell as a result of manipulation of the DNA of the host cell by recombinant DNA techniques, e.g., a stronger promoter. Similarly, the term “heterologous” (or exogenous or foreign or recombinant or non-native) polynucleotide refers to a polynucleotide that is not native to the host cell, a polynucleotide native to the host cell in which structural modifications, e.g., deletions, substitutions, and / or insertions, have been made by recombinant DNA techniques to alter the native polynucleotide, or a polynucleotide native to the host cell whose expression is quantitatively altered as a result of manipulation of the regulatory elements of the polynucleotide by recombinant DNA techniques, e.g., a stronger promoter, or a polynucleotide native to the host cell, but integrated not within its natural genetic environment as a result of genetic manipulation by recombinant DNA techniques. With respect to two or more polynucleotide sequences or two or more amino acid sequences, the term "heterologous” is used to characterize that the two or more polynucleotide sequences or two or more amino acid sequences are naturally not occurring in the specific combination with each other.

[0031] Variant polynucleotide and variant polypeptide sequences may be defined by their sequence identity when compared to a parent sequence. Sequence identity usually is provided as “% sequence identity” or “% identity”. For calculation of sequence identities, in a first step a sequence alignment is produced. According to this invention, a pairwise global alignment is produced, meaning that two sequences are aligned over their complete length, which is usually produced by using a mathematical approach, called alignment algorithm.

[0032] According to the invention, the alignment is generated by using the algorithm of Needleman and Wunsch (J. Mol. Biol. (1979) 48, p. 443-453). Preferably, the program “NEEDLE” (The European Molecular Biology Open Software Suite (EMBOSS)) is used for the purposes of the current invention, with using the programs default parameter (polynucleotides: gap open=10.0, gap extend=0.5 and matrix=EDNAFULL; polypeptides: gap open=10.0, gap extend=0.5 and matrix=EBLOSUM62). After aligning two sequences, in a second step, an identity value is determined from the alignment produced. For this purpose, the %-identity is calculated by dividing the number of identical residues by the length of the alignment region which is showing the respective sequence of the present invention over its complete length multiplied with 100: Coidentity = (identical residues I length of the alignment region which is showing the respective sequence of the present invention over its complete length) *100.

[0033] For calculating the percent identity of two nucleic acid sequences the same applies as for the calculation of percent identity of two amino acid sequences with some specifications. For nucleic acid sequences encoding for a protein the pairwise alignment shall be made over the complete length of the coding region of the sequence of this invention from start to stop codon excluding introns. Introns present in the other sequence, to which the sequence of this invention is compared, may also be removed for the pairwise alignment. Percent identity is then calculated by %-identity = (identical residues I length of the alignment region which is showing the sequence of the invention from start to stop codon excluding introns over their complete length) *100. After aligning two sequences, in a second step, an identity value is determined from the alignment produced. Moreover, the preferred alignment program for nucleic acid sequences implementing the Needleman and Wunsch algorithm (J. Mol. Biol. (1979) 48, p. 443-453) is “NEEDLE” (The European Molecular Biology Open Software Suite (EMBOSS)) with the programs default parameters (gapopen=10.0, gapextend=0.5 and matrix=EDNAFULL).

[0034] With regard to % identity between RNA and DNA sequences, a uracil within an RNA sequence is considered "identical" to a thymine within a DNA sequence.

[0035] Sequences, having identical or similar regions with a sequence of this invention, and which shall be compared with a sequence of this invention to determine % identity, can easily be identified by various ways that are within the skill in the art, for instance, using publicly available computer methods and programs such as BLAST, BLAST-2, available for example at NCBI.

[0036] Variant polypeptides may be defined by their sequence similarity when compared to a parent sequence. Sequence similarity usually is provided as “% sequence similarity” or “%-similarity”. % sequence similarity takes into account that defined sets of amino acids share similar properties, e.g. by their size, by their hydrophobicity, by their charge, or by other characteristics. Herein, the exchange of one amino acid with a similar amino acid may be called “conservative mutation”. Similar amino acids according to the invention are defined as follows, which shall also apply for determination of %-similarity according to this invention, which is also in accordance with the BLOSUM62 matrix as for example used by program “NEEDLE”, which is one of the most used amino acids similarity matrix for database searching and sequence alignments:

[0037] Amino acid A is similar to amino acids S

[0038] Amino acid D is similar to amino acids E; N

[0039] Amino acid E is similar to amino acids D; K; Q

[0040] Amino acid F is similar to amino acids W; Y

[0041] Amino acid H is similar to amino acids N; Y

[0042] Amino acid I is similar to amino acids L; M; V

[0043] Amino acid K is similar to amino acids E; Q; R

[0044] Amino acid L is similar to amino acids I; M; V

[0045] Amino acid M is similar to amino acids I; L; V

[0046] Amino acid N is similar to amino acids D; H; S

[0047] Amino acid Q is similar to amino acids E; K; R

[0048] Amino acid R is similar to amino acids K; Q

[0049] Amino acid S is similar to amino acids A; N; T

[0050] Amino acid T is similar to amino acids S

[0051] Amino acid V is similar to amino acids I; L; M

[0052] Amino acid W is similar to amino acids F; Y

[0053] Amino acid Y is similar to amino acids F; H; W

[0054] Conservative amino acid substitutions may occur over the full length of the sequence of a polypeptide sequence of a functional protein such as an enzyme. In one embodiment, such mutations are not pertaining the functional domains of an enzyme. In one embodiment, conservative mutations are not pertaining the catalytic centers of an enzyme. For calculation of sequence similarity, in a first step a sequence alignment is produced as described above. After aligning two sequences, in a second step, a similarity value is determined from the alignment produced. For this purpose, the %-similarity is calculated by dividing the number of identical residues plus the number of similar residues by the length of the alignment region which is showing the sequence of the invention over its complete length multiplied with 100: %-similarity = [(identical residues + similar residues) I length of the alignment region which is showing the sequence of the invention over its complete length] *100.

[0055] The term " phytopathogenic fungus", as used herein, refers to a fungus that is parasitic on a plant host. Phytopathogenic fungi include fungi of the phyla Ascomycota and Basidiomycota. The asexual reproduction stage (anamorph) of such fungus may be known under a different name than its sexual reproduction stage (teleomorph). For example, the anamorph of Botryotinia fuckeliana (syn. Botryotinia cinerea) is known as Botrytis cinerea. For the purpose of the present invention, the names of the Ascomycota and Basidiomycota used herein are meant to refer the fungal species per se rather than to a particular reproduction stage thereof.

[0056] The term " CYP51 genes ", as used herein, refers to genes encoding a cytochrome P450 sterol 14 alpha-demethylase (CYP51) and homologues thereof. A fungal phytopathogen can have more than one CYP51 gene.

[0057] The term "dsRNA molecule", as used herein for designating a subject matter of the invention, refers to a molecule comprising one, two or more polyribonucleotide strands capable of forming at least one region of double stranded RNA. Thus, the term "dsRNA molecule of the invention" includes molecules, wherein only part of the RNA, e.g. at least 70%, at least 80% or at least 90%, or all of the RNA is present as double stranded RNA. For example, the term "dsRNA molecule" includes molecules consisting of one, two or more polyribonucleotide strands. Also included by the term are molecules additionally comprising further chemical groups, for example groups stabilizing the regions of double stranded RNA as described herein.

[0058] The effect of the dsRNA molecules of the invention is assumed to be due to RNA interference.

[0059] The terms "RNAi" and "RNA interference", used herein, refer to a process of sequence-specific post-transcriptional gene silencing mediated by double-stranded RNA. In the RNAi process, a double-stranded RNA is processed into relatively small fragments, typically 20-25 nucleotides in length, which become part of an RNA-induced silencing complex (RISC) which binds to and cleaves complementary mRNA and thus prevents the mRNA from being used as a template for translation.

[0060] The term "antisense interference" also refers to a process of sequence-specific post- transcriptional gene silencing. In antisense interference, a single-stranded antisense RNA (antisense-ssRNA) that is substantially complementary to at least a part of a target gene causes inhibition of the target gene expression. It is assumed that in this process double-stranded RNA is formed by hybridization of the antisense ssRNA hybridizes with complementary mRNA and inhibits the target gene expression using the RNAi mechanism.

[0061] An "antisense sequence" as comprised by the dsRNA molecules of the present invention is an RNA sequence that is substantially complementary to the corresponding sense sequence. "Complementary" polynucleotides are those capable of base pairing according to the Watson- Crick complementarity rules. Specifically, base pairs will form between purines and pyrimidines including guanine paired with cytosine (G:C) and adenine paired with either thymine (A:T) in case of DNA, or adenine paired with uracil (A:ll) in the case of RNA. It is understood that two polynucleotides may hybridize to each other even if they are not completely complementary to each other, provided that each has at least one region that is substantially complementary to the other.

[0062] The term "hybridization", as used herein, includes any process by which a polynucleotide strand joins with a complementary strand through base pairing. (Coombs: Dictionary of Biotechnology, Stockton Press, New York, 1994). Hybridization and the strength of hybridization (i.e., the strength of the association between the two complementary strands) is impacted by factors such as the degree of complementarity between the strands, the stringency of the conditions involved, the melting temperature of the formed double strand, and the G:C ratio within the strands. The melting temperature (Tm) is the temperature at which a population of doublestranded polynucleotides becomes half dissociated into single strands. Tm can be calculated using equations well known in the art. An estimate for the Tm value of a polynucleotide in an aqueous 1 M NaCI solution is given by the equation: Tm=81.5+0.41(% G+C) (cf. , e.g., Anderson and Young: Quantitative Filter Hybridization, in Nucleic Acid Hybridization, 1985). Stringent conditions are known to those skilled in the art (cf., e.g., Current Protocols in Molecular Biology, John Wiley & Sons, N.Y., 6.3.1 -6.3.6, 1989). In particular, the term "stringent conditions", as used herein, refers to hybridization to filter-bound nucleic acid in 6x sodium chloride / sodium citrate (SSC) at about 45°C followed by one or more washes in 0.2x SSC / 0.1 % SOS (sodium dodecyl sulfate) at about 50-65°C.

[0063] The term "expression", as used herein with respect to a gene sequence, refers to the translation of the coding sequence to a polypeptide. Inhibition of gene expression can become detectable on the level of mRNA, on the level of polypeptide or both. Methods for assessing changes in the mRNA level or the protein level of a gene are well-known in the art. For example, the change in the mRNA level of a gene can be assessed by quantitative real-time PCR (qRT-PCR) or Northern Blot.

[0064] "Controlling" a phytopathogenic fungus, as used herein, includes measures for preventing the infestation of a plant with said pathogen as well as measures for com batting or curing the pathogen infestation of a plant. The term "combatting" refers to the reduction of the pathogen infestation. The term "curing" refers to the eradication of the pathogen infestation. A "plant-compatible" carrier, as used herein, is a compound or a mixture of compounds that, under the conditions of its use, does not exert unacceptable phytotoxic activity to the treated plant.

[0065] The term "plant" is used herein to designate a whole plant at any stage of development as well as a part or derivative thereof, and thus includes, for instance, a plant cell, a plant cell population, a plant tissue (e.g. a meristematic tissue, callus tissue), a plant organ (e.g. stem, leaf, root, ovule, stamen), a reproductive form or reproductive part of a plant (e.g. a seed, tuber, cutting, gametophyte, sporophyte, pollen, microspore, embryo). A plant cell or plant cell population can be isolated (e.g. in suspension culture) or comprised in a plant tissue, plant organ or whole plant of any developmental stage.

[0066] A "transgenic" plant is a whole plant or part thereof that has been altered using recombinant DNA technology to contain a nucleic acid sequence which would otherwise not be present in said plant or which would be expressed to a considerably lower extent. DNA which is introduced via recombinant DNA technology in the genome of a plant is frequently called heterologous DNA or transgene. This heterologous DNA can be introduced with techniques, which result in random insertion of the heterologous DNA in the plant genome, like Agrobacterium mediated transformation or via a particle gun, but may also transferred to preselected locations in the genome via targeted integration. Methods of targeted integration frequently use oligonucleotides or proteins like CRISPR / Cas, zinc-finger nucleases, TALENs or meganucleases to insert the heterologous DNA at the preselected location. The process of plant transformation usually produces several transformation events, which may differ in the genomic locus in which a transgene has been integrated. Plants comprising a specific transgene on a specific genomic locus are usually described as comprising a specific “event”, which is referred to by a specific event name. The term "transgenic plant" also includes the transgenic progeny of a transgenic plant. A transgenic plant of the present invention may result from crossing a transgenic plant of the invention with a non-transgenic plant or with another transgenic plant of the invention or with a transgenic plant having a different transgene. In particular, the term "transgenic plant" also comprises true breeding transgenic plants which are obtained by repeated inbreeding steps.

[0067] A "transcriptional template" of an RNA sequence is a DNA sequence that can serve as a template for the generation of the RNA by enzymatic transcription with an RNA polymerase. The term "promoter", when used herein in the context of the nucleic acid sequence(s) of the invention, refers to the singular as well as to the plural, unless explicitly stated otherwise. A "promoter", as used herein, is a DNA sequence which, when ligated to a DNA sequence of interest, is capable of controlling the transcription of said DNA sequence into RNA. A promoter is typically located 5' (e.g., upstream) of the DNA sequence of interest whose transcription into mRNA it controls (e.g., proximal to the transcriptional start site), and provides a site for specific binding by RNA polymerase and other transcription factors for initiation of transcription. A promoter can be a constitutive promoter or a regulated promoter. A "regulated promoter" is a promoter that drives transcription not constitutively but in a temporally and / or spatially restricted manner. A promoter is regulated if the amount of RNA produced under the control of the activated promoter is at least 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 200% or 300% higher than the amount of RNA produced in parts of the plant or at periods of time, where the promoter is not activated. Regulated promoters include inducible promoters, tissue-specific promoters and development specific promoters. Tissuespecific or development-specific promoters facilitate transcription of a sequence of interest in specific tissues, organs or cell types, or at specific different developmental stages while leaving the rest of the organism unmodified. In the case of plants, such promoters might specifically influence expression of genes in the roots, inflorescence, cereal ears, fruits, or seeds, or during the vegetative, flowering, or seed-setting stage. Inducible promoters facilitate transcription of a sequence of interest in the presence or absence of particular chemical compounds (e.g. an alcohol, tetracycline, a steroid, or a metal) or depending on particular physical conditions (e.g. the presence or absence of light, low or high temperatures).

[0068] The term "phytopathogen-tolerant" is used herein to designate a transgenic plant of the invention capable of reducing or preventing the growth and / or propagation of the phytopathogen. The tolerance to the phytopathogen can be transient, i.e. present only for a limited period of time, for example due to a transient expression of the antisense RNA or the dsRNA molecule of the invention. A plant that is "tolerant" to a phytopathogen is infested less severely and / or less frequently by the phytopathogen. Severity of the fungal or oomycetes infestation can be determined based on the disease symptoms observed after the plant was inoculated with or attacked by the phytopathogen. The disease symptoms depend on the nature (species, variant) of the phytopathogen and of the plant. Symptoms of fungal or oomycete infestations of plants include, but are not limited to, premature bleaching of cereal ears and / or leaves; necrotic lesions on the exterior surface of the florets and glume; kernel atrophy; awn deformation; discoloration of kernels and / or spikelets; visible pathogen growth on leaves, stem, and / or cereal ears.

[0069] The term "fungicidally effective amount" denotes an amount of a composition or of a compound, which is sufficient for controlling harmful fungi on plants or in the protection of stored products or harvest or of materials and which does not result in a substantial damage to the treated plants, the treated stored products or harvest, or to the treated materials. Such an amount can vary in a broad range and is dependent on various factors, such as the fungal species to be controlled, the treated plant, stored product, harvest or material, the climatic conditions and the specific compound used. Particular embodiments of the invention regarding the RNA:

[0070] The present invention refers to mixtures comprising: a) at least one RNA comprising at least 18, 19, 20, 21, 25, 50, 100, 150, 200, 250, 300, 350, 400, 450, or 500 contiguous nucleotides forming a nucleotide sequence having, in growing order of preference, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with a segment of a nucleotide sequence of the transcribed region of a CYP51 gene, or the reverse complement nucleotide sequence thereof, and b) at least one chemical or biological fungicide.

[0071] In embodiment 1 , the CYP51 gene is from Erysiphe necator also known as Uncinula necator (EPPO Code: IINCINE), Erysiphe cichoracearum, also known as: Golovinomyces cichoracearum (EPPO Code: ERYSCI), Erysiphe neolycopersici, also known as: Oidium neolycopersici (EPPO Code: OIDINL), or Botrytis cinerea (EPPO Code: BOTRCI). The EPPO Code refers to the species code defined by the European and Mediterranean Plant Protection Organization (EPPO).

[0072] In embodiment 2, the CYP51 gene encodes an amino acid sequence of the encoded protein having, in growing order of preference, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with a protein sequence selected from the group consisting of: SEQ ID Nos: 1 , 88, 119 and 57.

[0073] One example for sequence variation in the amino acid sequence is the Y136F mutation known to occur in DMI fungicide resistant Erysiphe necator strains.

[0074] Preferably, the CYP51 gene comprises a nucleotide sequence selected from the group consisting of: SEQ ID Nos: 2, 3, 4, 89, 90, 91 , 120, 121 , 122, 58, 59 and 60.

[0075] The CYP51 gene of Erysiphe necator comprises nucleotide sequences described by SEQ ID Nos: 2, 3 and 4.

[0076] The CYP51 gene of Erysiphe cichoracearum comprises nucleotide sequences described by SEQ ID Nos: 89, 90 and 91.

[0077] The CYP51 gene of Erysiphe neolycopersici comprises nucleotide sequences described by SEQ ID Nos: 120, 121 and 122.

[0078] The CYP51 gene of Botrytis cinerea comprises nucleotide sequences described by SEQ ID Nos: 58, 59 and 60.

[0079] In embodiment 3, the at least one RNA is selected from: a. an RNA comprising at least 18, 19, 20, 21 , 25, 50, 100, 150, 200, 250, 300, 350, 400, 450, or 500 contiguous nucleotides forming a nucleotide sequence having, in growing order of preference, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with a segment of a nucleotide sequence of the transcribed region of a CYP51 gene, or b. an RNA comprising at least 18, 19, 20, 21 , 25, 50, 100, 150, 200, 250, 300, 350, 400, 450, or 500 contiguous nucleotides forming a nucleotide sequence, which is the reverse complement to a nucleotide sequence having, in growing order of preference, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with a segment of a nucleotide sequence of the transcribed region of a CYP51 gene, or c. a dsRNA comprising a sense nucleotide sequence of an RNA of a. and an anti-sense nucleotide sequence of an RNA of b., wherein the arrangement of the RNA of a. and the RNA of b. within the dsRNA molecule allows hybridization of the RNA of a. and the RNA of b. at room temperature.

[0080] Preferably, the at least one RNA comprises a nucleotide sequence of 300 to 500 contiguous nucleotides having, in growing order of preference, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with a segment of a nucleotide sequence of the transcribed region of a CYP51 gene.

[0081] Also preferred, the at least one RNA comprises a nucleotide sequence of 350 to 500 contiguous nucleotides having, in growing order of preference, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with a segment of a nucleotide sequence of the transcribed region of a CYP51 gene.

[0082] In embodiment 4, the at least one RNA is a dsRNA comprising: a) at least 18, 19, 20, 21 , 25, 50, 100, 150, 200, 250, 300, 350, 400, 450, or 500 contiguous nucleotides forming a nucleotide sequence having, in growing order of preference, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with a segment of a nucleotide sequence of the transcribed region of a CYP51 gene and b) comprising at least 18, 19, 20, 21 , 25, 50, 100, 150, 200, 250, 300, 350, 400, 450, or 500 contiguous nucleotides forming a nucleotide sequence, which is the reverse complement to a nucleotide sequence having, in growing order of preference, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with a segment of a nucleotide sequence of the transcribed region of a CYP51 gene, wherein the arrangement of the RNA segment of a) and the RNA segment of b) within the dsRNA molecule allows hybridization of the RNA segment of a) and the RNA segment of b) at room temperature.

[0083] In embodiment 5, the at least one RNA is selected from: a. an RNA comprising a nucleotide sequence having, in growing order of preference, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with a nucleotide sequence selected from the group consisting of SEQ ID Nos: 5, 8, 11, 14,

[0084] 17, 20, 23, 26, 29, 92, 95, 98, 101, 104, 107, 110, 113, 116, 123, 126, 129, 132, 135, 138, 141 , 144, 147, 33, 37, 41 , 45, 48, 51, 54, 61 , 64, 67, 70, 73, 76, 79, 82 and 85, b. an RNA comprising a nucleotide sequence having, in growing order of preference, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with a nucleotide sequence selected from the group consisting of SEQ ID Nos: 6, 9, 12, 15,

[0085] 18, 21 , 24, 27, 30, 93, 96, 99, 102, 105, 108, 111 , 114, 117, 124, 127, 130, 133, 136, 139, 142, 145, 148, 34, 38, 42, 46, 49, 52, 55, 62, 65, 68, 71, 74, 77, 80, 83, 86, 274, 276, 278, 280, 282, 284, 286 and 288, and c. an RNA comprising a nucleotide sequence having, in growing order of preference, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with a nucleotide sequence selected from the group consisting of SEQ ID Nos: 7, 10, 13, 16, 19, 22, 25, 28, 31, 94, 97, 100, 103, 106, 109, 112, 115, 118, 125, 128, 131 , 134, 137, 140, 143, 146, 149, 35, 39, 43, 47, 50, 53, 56, 63, 66, 69, 72, 75, 78, 81, 84 , 87, 275, 277, 279, 281 , 283, 285, 287 and 289.

[0086] Wherein RNAs of SEQ ID Nos: 5, 8, 11 , 14, 17, 20, 23, 26, 29, 6, 9, 12, 15, 18, 21 , 24, 27, 30, 7, 10, 13, 16, 19, 22, 25, 28, 31, 33, 37, 41 , 45, 34, 38, 42, 46, 35, 39, 43, 47, 274, 276, 275 and 277 are best used to control Erysiphe necator.

[0087] Wherein RNAs of SEQ ID Nos: 92, 95, 98, 101, 104, 107, 110, 113, 116, 93, 96, 99, 102, 105, 108, 111 , 114, 117, 94, 97, 100, 103, 106, 109, 112, 115, 118, 278, 280, 279 and 281 are best used to control Erysiphe cichoracearum.

[0088] Wherein RNAs of SEQ ID Nos: 123, 126, 129, 132, 135, 138, 141, 144, 147, 124, 127, 130, 133, 136, 139, 142, 145, 148, 125, 128, 131, 134, 137, 140, 143, 146, 149282, 284, 283 and 28 are best used to control Erysiphe neolycopersici.

[0089] Wherein RNAs of SEQ ID Nos: 61, 64, 67, 70, 73, 76, 79, 82, 85, 62, 65, 68, 71 , 74, 77, 80, 83, 86, 63, 66, 69, 72, 75, 78, 81 , 84, 87, 286, 288, 287 and 289 are best used to control Botrytis cinerea.

[0090] In embodiment 6, at least one RNA sequences to control Erysiphe necator is described by SEQ ID Nos: 33, 37, 41, 45, 34, 38, 42, 46, 35, 39, 43, 47, 274, 276, 275 or 277.

[0091] The nucleotide sequences of the RNAs are not necessarily restricted to the coding region of a target gene. Such RNAs can also comprise part of the 5-prime untranslated region or sequence regions of additional target genes.

[0092] Non-limiting examples of RNA sequences comprising parts of the 5-prime untranslated region are described by SEQ ID Nos: 5, 6, 7, 92, 93, 94, 123, 124, 125, 61, 62, and 63.

[0093] Non-limiting examples of RNA sequences comprising parts of additional target genes (chimeric RNAs) are described by SEQ ID Nos: 48, 51, 54, 49, 52, 55, 50, 53 and 56.

[0094] Preferred RNAs comprise 18, 19, 20, 21 , 25, 50, 100, 150, 200, 250, 300, 350, 400, 450, or 500 contiguous nucleotides forming a nucleotide sequence having, in growing order of preference, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with a nucleotide sequence from nucleotide 300 to nucleotide 1000, preferably from nucleotide 340 to nucleotide 960, of a nucleotide sequence selected the group consisting of: SEQ ID Nos: 4, 91, 122, and 60.

[0095] Preferably the RNAs comprise between 300 and 500, more preferred between 350 and 500 contiguous nucleotides selected from a nucleotide sequence from nucleotide 300 to nucleotide 1000, preferably from nucleotide 340 to nucleotide 960, of a nucleotide sequence selected the group consisting of: SEQ ID Nos: 4, 91 , 122, and 60. Preferred RNAs comprise also the reverse complement sequence of this region and preferred dsRNAs comprise a sense nucleotide sequence covering between 300 and 500, more preferred between 350 and 500 contiguous nucleotides selected from a nucleotide sequence from nucleotide 300 to nucleotide 1000, preferably from nucleotide 340 to nucleotide 960, of a nucleotide sequence selected the group consisting of: SEQ ID Nos: 4, 91 , 122, and an anti-sense nucleotide sequence covering between 300 and 500, more preferred between 350 and 500 contiguous nucleotides selected from a nucleotide sequence from nucleotide 300 to nucleotide 1000, preferably from nucleotide 340 to nucleotide 960, of a nucleotide sequence selected the group consisting of: SEQ ID Nos: 4, 91, 122, wherein the arrangement of the sense nucleotide sequence and the antisense nucleotide sequence within the dsRNA molecule allows hybridization of the sense nucleotide sequence and the antisense nucleotide sequence at room temperature and the sense and antisense nucleotide sequences are preferably selected from the same SEQ ID Nos: 4, 91 or 122. In embodiment 7 the RNAs of the mixtures are used to control Erysiphe necator comprise an RNA selected from: a. an RNA comprising 18, 19, 20, 21, 25, 50, 100, 150, 200, 250, 300, 350, 400, 450, or 500 contiguous nucleotides forming a nucleotide sequence having, in growing order of preference, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with a nucleotide sequence from nucleotide 300 to nucleotide 1000, preferably from nucleotide 340 to nucleotide 960, of a nucleotide sequence of: SEQ ID No: 4, b. an RNA comprising 18, 19, 20, 21, 25, 50, 100, 150, 200, 250, 300, 350, 400, 450, or 500 contiguous nucleotides forming a nucleotide sequence having, in growing order of preference, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with the reverse complement of the nucleotide sequence from nucleotide 300 to nucleotide 1000, preferably from nucleotide 340 to nucleotide 960, of a nucleotide sequence of: SEQ ID No: 4, c. a dsRNA comprising a sense nucleotide sequence of 300 to 500 contiguous nucleotides forming a nucleotide sequence having, in growing order of preference, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with a nucleotide sequence from nucleotide 300 to nucleotide 1000, preferably from nucleotide 340 to nucleotide 960, of a nucleotide sequence of: SEQ ID No: 4 and an anti-sense nucleotide sequence comprising 300 to 500 contiguous nucleotides forming a nucleotide sequence having, in growing order of preference, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with the reverse complement of the nucleotide sequence from nucleotide 300 to nucleotide 1000, preferably from nucleotide 340 to nucleotide 960, of a nucleotide sequence of: SEQ ID No: 4, wherein the arrangement of the sense nucleotide sequence and the antisense nucleotide sequence within the dsRNA molecule allows hybridization of the sense nucleotide sequence and the antisense nucleotide sequence at room temperature. d. an RNA comprising a nucleotide sequence having, in growing order of preference, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with a nucleotide sequence selected from the group consisting of: 34, 274, 276, 35, 275 and 277, e. a dsRNA comprising a sense nucleotide sequence having, in growing order of preference, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with a nucleotide sequence selected from the group consisting of: SEQ ID No. 34, 274 or 276, and comprising an antisense nucleotide sequence having, in growing order of preference, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with a nucleotide sequence selected from the group consisting of: SEQ ID No. 35, 275 or 277 wherein the arrangement of the sense nucleotide sequence and the antisense nucleotide sequence within the dsRNA molecule allows hybridization of the sense nucleotide sequence and the antisense nucleotide sequence at room temperature, f. a dsRNA comprising a sense nucleotide sequence having, in growing order of preference, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with a nucleotide sequence selected from the group consisting of: SEQ ID No. 274, and comprising an antisense nucleotide sequence having, in growing order of preference, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with a nucleotide sequence selected from the group consisting of: SEQ ID No. 275 wherein the arrangement of the sense nucleotide sequence and the antisense nucleotide sequence within the dsRNA molecule allows hybridization of the sense nucleotide sequence and the antisense nucleotide sequence at room temperature, and g. a dsRNA comprising a sense nucleotide sequence having, in growing order of preference, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with a nucleotide sequence selected from the group consisting of: SEQ ID No. 276, and comprising an antisense nucleotide sequence having, in growing order of preference, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with a nucleotide sequence selected from the group consisting of: SEQ ID No. 277 wherein the arrangement of the sense nucleotide sequence and the antisense nucleotide sequence within the dsRNA molecule allows hybridization of the sense nucleotide sequence and the antisense nucleotide sequence at room temperature.

[0096] In embodiment 8 the RNAs of the mixtures are used to control Erysiphe cichoracearum comprise an RNA selected from: a. an RNA comprising 18, 19, 20, 21 , 25, 50, 100, 150, 200, 250, 300, 350, 400, 450, or 500 contiguous nucleotides forming a nucleotide sequence having, in growing order of preference, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with a nucleotide sequence from nucleotide 300 to nucleotide 1000, preferably from nucleotide 340 to nucleotide 960, of a nucleotide sequence of: SEQ ID No: 91 , b. an RNA comprising 18, 19, 20, 21 , 25, 50, 100, 150, 200, 250, 300, 350, 400, 450, or 500 contiguous nucleotides forming a nucleotide sequence having, in growing order of preference, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with the reverse complement of the nucleotide sequence from nucleotide 300 to nucleotide 1000, preferably from nucleotide 340 to nucleotide 960, of a nucleotide sequence of: SEQ ID No: 91 , c. a dsRNA comprising a sense nucleotide sequence of 300 to 500 contiguous nucleotides forming a nucleotide sequence having, in growing order of preference, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with a nucleotide sequence from nucleotide 300 to nucleotide 1000, preferably from nucleotide 340 to nucleotide 960, of a nucleotide sequence of: SEQ ID No: 91 and an anti-sense nucleotide sequence comprising 300 to 500 contiguous nucleotides forming a nucleotide sequence having, in growing order of preference, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with the reverse complement of the nucleotide sequence from nucleotide 300 to nucleotide 1000, preferably from nucleotide 340 to nucleotide 960, of a nucleotide sequence of: SEQ ID No: 91 , wherein the arrangement of the sense nucleotide sequence and the antisense nucleotide sequence within the dsRNA molecule allows hybridization of the sense nucleotide sequence and the antisense nucleotide sequence at room temperature, d. an RNA comprising a nucleotide sequence having, in growing order of preference, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with a nucleotide sequence selected from the group consisting of: 278, 280, 279 and 281, e. a dsRNA comprising a sense nucleotide sequence having, in growing order of preference, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with a nucleotide sequence selected from the group consisting of: SEQ ID No. 278, and comprising an antisense nucleotide sequence having, in growing order of preference, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with a nucleotide sequence selected from the group consisting of: SEQ ID No. 279, wherein the arrangement of the sense nucleotide sequence and the antisense nucleotide sequence within the dsRNA molecule allows hybridization of the sense nucleotide sequence and the antisense nucleotide sequence at room temperature, and f. a dsRNA comprising a sense nucleotide sequence having, in growing order of preference, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with a nucleotide sequence selected from the group consisting of: SEQ ID No. 280, and comprising an antisense nucleotide sequence having, in growing order of preference, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with a nucleotide sequence selected from the group consisting of: SEQ ID No. 281 wherein the arrangement of the sense nucleotide sequence and the antisense nucleotide sequence within the dsRNA molecule allows hybridization of the sense nucleotide sequence and the antisense nucleotide sequence at room temperature.

[0097] In embodiment 9 the RNAs of the mixtures are used to control Erysiphe neolycopersici comprise an RNA selected from: a. an RNA comprising 18, 19, 20, 21 , 25, 50, 100, 150, 200, 250, 300, 350, 400, 450, or 500 contiguous nucleotides forming a nucleotide sequence having, in growing order of preference, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with a nucleotide sequence from nucleotide 300 to nucleotide 1000, preferably from nucleotide 340 to nucleotide 960, of a nucleotide sequence of: SEQ ID No: 122, b. an RNA comprising 18, 19, 20, 21 , 25, 50, 100, 150, 200, 250, 300, 350, 400, 450, or 500 contiguous nucleotides forming a nucleotide sequence having, in growing order of preference, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with the reverse complement of the nucleotide sequence from nucleotide 300 to nucleotide 1000, preferably from nucleotide 340 to nucleotide 960, of a nucleotide sequence of: SEQ ID No: 122, c. a dsRNA comprising a sense nucleotide sequence of 300 to 500 contiguous nucleotides forming a nucleotide sequence having, in growing order of preference, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with a nucleotide sequence from nucleotide 300 to nucleotide 1000, preferably from nucleotide 340 to nucleotide 960, of a nucleotide sequence of: SEQ ID No: 122 and an anti-sense nucleotide sequence comprising 300 to 500 contiguous nucleotides forming a nucleotide sequence having, in growing order of preference, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with the reverse complement of the nucleotide sequence from nucleotide 300 to nucleotide 1000, preferably from nucleotide 340 to nucleotide 960, of a nucleotide sequence of: SEQ ID No: 122, wherein the arrangement of the sense nucleotide sequence and the antisense nucleotide sequence within the dsRNA molecule allows hybridization of the sense nucleotide sequence and the antisense nucleotide sequence at room temperature, d. an RNA comprising a nucleotide sequence having, in growing order of preference, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with a nucleotide sequence selected from the group consisting of: 282, 284, 283, and 285, e. a dsRNA comprising a sense nucleotide sequence having, in growing order of preference, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with a nucleotide sequence selected from the group consisting of: SEQ ID No. 282, and comprising an antisense nucleotide sequence having, in growing order of preference, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with a nucleotide sequence selected from the group consisting of: SEQ ID No. 283, wherein the arrangement of the sense nucleotide sequence and the antisense nucleotide sequence within the dsRNA molecule allows hybridization of the sense nucleotide sequence and the antisense nucleotide sequence at room temperature, and f. a dsRNA comprising a sense nucleotide sequence having, in growing order of preference, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with a nucleotide sequence selected from the group consisting of: SEQ ID No. 284, and comprising an antisense nucleotide sequence having, in growing order of preference, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with a nucleotide sequence selected from the group consisting of: SEQ ID No. 285 wherein the arrangement of the sense nucleotide sequence and the antisense nucleotide sequence within the dsRNA molecule allows hybridization of the sense nucleotide sequence and the antisense nucleotide sequence at room temperature.

[0098] In embodiment 10 the RNAs of the mixtures are used to control Botrytis cinerea comprise an RNA selected from: a. an RNA comprising 18, 19, 20, 21 , 25, 50, 100, 150, 200, 250, 300, 350, 400, 450, or 500 contiguous nucleotides forming a nucleotide sequence having, in growing order of preference, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with a nucleotide sequence from nucleotide 300 to nucleotide 1000, preferably from nucleotide 340 to nucleotide 960, of a nucleotide sequence of: SEQ ID No: 60, b. an RNA comprising 18, 19, 20, 21 , 25, 50, 100, 150, 200, 250, 300, 350, 400, 450, or 500 contiguous nucleotides forming a nucleotide sequence having, in growing order of preference, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with the reverse complement of the nucleotide sequence from nucleotide 300 to nucleotide 1000, preferably from nucleotide 340 to nucleotide 960, of a nucleotide sequence of: SEQ ID No: 60, c. a dsRNA comprising a sense nucleotide sequence of 300 to 500 contiguous nucleotides forming a nucleotide sequence having, in growing order of preference, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with a nucleotide sequence from nucleotide 300 to nucleotide 1000, preferably from nucleotide 340 to nucleotide 960, of a nucleotide sequence of: SEQ ID No: 60 and an anti-sense nucleotide sequence comprising 300 to 500 contiguous nucleotides forming a nucleotide sequence having, in growing order of preference, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with the reverse complement of the nucleotide sequence from nucleotide 300 to nucleotide 1000, preferably from nucleotide 340 to nucleotide 960, of a nucleotide sequence of: SEQ ID No: 60, wherein the arrangement of the sense nucleotide sequence and the antisense nucleotide sequence within the dsRNA molecule allows hybridization of the sense nucleotide sequence and the antisense nucleotide sequence at room temperature, d. an RNA comprising a nucleotide sequence having, in growing order of preference, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with a nucleotide sequence selected from the group consisting of: 286, 288, 287 and 289, e. a dsRNA comprising a sense nucleotide sequence having, in growing order of preference, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with a nucleotide sequence selected from the group consisting of: SEQ ID No. 286, and comprising an antisense nucleotide sequence having, in growing order of preference, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with a nucleotide sequence selected from the group consisting of: SEQ ID No. 287, wherein the arrangement of the sense nucleotide sequence and the antisense nucleotide sequence within the dsRNA molecule allows hybridization of the sense nucleotide sequence and the antisense nucleotide sequence at room temperature, and f. a dsRNA comprising a sense nucleotide sequence having, in growing order of preference, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with a nucleotide sequence selected from the group consisting of: SEQ ID No. 288, and comprising an antisense nucleotide sequence having, in growing order of preference, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with a nucleotide sequence selected from the group consisting of: SEQ ID No. 289 wherein the arrangement of the sense nucleotide sequence and the antisense nucleotide sequence within the dsRNA molecule allows hybridization of the sense nucleotide sequence and the antisense nucleotide sequence at room temperature.

[0099] It is a common observation that plants are frequently attacked by more than one phytopathogenic fungal species. Thus, it is preferred that the mixtures comprise RNAs selected to control several phytopathogenic fungal species. A preferred combination are RNAs selected to control at least one of the species selected from E. necator, E. cichoracearum and E. neolycopersici and RNAs selected to control B. cineria.

[0100] These RNAs may be present as separate single strand or double strand RNA molecules or may be present as different segment of one single strand or double strand RNA.

[0101] Accordingly, in embodiment 11 of the invention the mixtures comprise: a. at least one RNA ,or RNA segment, comprising at least 18, 19, 20, 21, 25, 50, 100, 150, 200, 250, 300, 350, 400, 450, or 500 contiguous nucleotides forming a nucleotide sequence having , in growing order of preference, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with a segment of a nucleotide sequence of the transcribed region of a CYP51 gene encoding a protein sequence selected from the group consisting of: SEQ ID Nos: 1 , 88 and 119, and b. at least one RNA, or RNA segment, comprising at least 18, 19, 20, 21, 25, 50, 100, 150, 200, 250, 300, 350, 400, 450, or 500 contiguous nucleotides forming a nucleotide sequence having , in growing order of preference, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with a segment of a nucleotide sequence of the transcribed region of a CYP51 gene encoding a protein sequence of: SEQ ID No: 57.

[0102] In embodiment 12 of the invention the mixtures comprise: a. at least one RNA ,or RNA segment, comprising at least 18, 19, 20, 21 , 25, 50, 100, 150, 200, 250, 300, 350, 400, 450, or 500 contiguous nucleotides forming a nucleotide sequence having , in growing order of preference, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with a segment of a nucleotide sequence selected from the group consisting of: SEQ ID No: 2, 3, 4, 89, 90, 91, 120, 121 and 122, and b. at least one RNA, or RNA segment, comprising at least 18, 19, 20, 21 , 25, 50, 100, 150, 200, 250, 300, 350, 400, 450, or 500 contiguous nucleotides forming a nucleotide sequence having , in growing order of preference, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with a segment of a nucleotide sequence of: SEQ ID Nos: 58, 59 and 60.

[0103] In embodiment 13 of the invention the mixtures comprise: a. at least one RNA selected from an RNA described in embodiment 7, 8 or 9, and b. at least one RNA, RNA selected from an RNA described in embodiment 10.

[0104] In embodiment 14 of the invention the mixtures comprise: a. at least one RNA selected from an RNA described in embodiment 7a, 7b, 7c, 8a, 8b, 8c, 9a, 9b, or 9c, and b. at least one RNA, RNA selected from an RNA described in embodiment 10a, 10b or 10c.

[0105] In embodiment 15 of the invention the mixtures comprise: c. at least one RNA selected from an RNA described in embodiment 7a, 8a or 9a, and d. at least one RNA, RNA selected from an RNA described in embodiment 10a.

[0106] In embodiment 16 of the invention the mixtures comprise: a. at least one RNA selected from an RNA described in embodiment 7a and b. at least one RNA, RNA selected from an RNA described in embodiment 10a.

[0107] In one embodiment 17 of the invention the mixtures comprise: a. at least one RNA selected from an RNA described in embodiment 7d, 8d or 9d, and b. at least one RNA, RNA selected from an RNA described in embodiment 10d.

[0108] In one embodiment 18 of the invention the mixtures comprise: a. at least one RNA selected from an RNA described in embodiment 7e, 7f, 7g, 8e, 8f, 9e or 9f, and b. at least one RNA, RNA selected from an RNA described in embodiment 10a, 10e or 10f. In one embodiment 19 of the invention the mixtures comprise: a. at least one RNA selected from an RNA described in embodiment 7e, 7f, or 7g, and b. at least one RNA, RNA selected from an RNA described in embodiment 10a, 10e or 10f.

[0109] In one embodiment 20 of the invention the mixtures comprise: a. at least one RNA selected from an RNA described in embodiment 7e, and b. at least one RNA, RNA selected from an RNA described in embodiment 10a, 10e or 10f. Preferred RNA combinations to form dsRNA in all embodiments comprising dsRNA are RNAs described by the following SEQ ID Nos: 6 and 7, 9 and 10, 12 and 13, 15 and 16, 18 and 19, 21 and 22, 24 and 25, 27 and 28, 30 and 31, 34 and 35, 38 and 39, 42 and 43, 46 and 47, 49 and 50, 52 and 53, 55 and 56, 274 and 275, 276 and 277, 93 and 94, 96 and 97, 99 and 100, 102 and 103, 105 and 106, 108 and 109, 111 and 112, 114 and 115, 117 and 118, 278 and 279, 280 and 281, 124 and 125, 127 and 128, 130 and 131 , 133 and 134, 136 and 137, 139 and 140, 142 and 143, 145 and 146, 148 and 149, 282 and 283, 284 and 285, 62 and 63, 65 and 66, 68 and 69, 71 and 72, 74 and 75, 77 and 78, 80 and 81 , 83 and 84, 86 and 87, 286 and 287, 288 and 289.

[0110] Table 1:

[0111] The mixtures of at least one RNA comprising at least 18, 19, 20, 21, 25, 50, 100, 150, 200, 250, 300, 350, 400, 450, or 500 contiguous nucleotides forming a nucleotide sequence having at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with a segment of a nucleotide sequence of the transcribed region of a CYP51 gene, or the reverse complement nucleotide sequence thereof, and at least one chemical or biological fungicide are not limited to the described groups of RNAs of embodiments 1 to 20, but can comprise any RNA or dsRNA encompassed by and / or described in at least one of those groups comprising at least 18, 19, 20, 21, 25, 50, 100, 150, 200, 250, 300, 350, 400, 450, or 500 contiguous nucleotides forming a nucleotide sequence having at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with a segment of a nucleotide sequence of the transcribed region of a CYP51 gene. Preferred RNAs comprise at least 300 to 500, preferably 350 to 500, contiguous nucleotides forming a nucleotide sequence having at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with a segment of a nucleotide sequence of the transcribed region of a CYP51 gene. More preferred are RNAs comprising at least 300 to 500, preferably 350 to 500, contiguous nucleotides forming a nucleotide sequence having at least at least 95%, at least 98%, at least 99%, or 100% sequence identity with a segment of a nucleotide sequence of the transcribed region of a CYP51 gene.

[0112] Even more preferred are RNAs comprising at least 300 to 500, preferably 350 to 500, contiguous nucleotides forming a nucleotide sequence having at least 99%, or 100% sequence identity with a segment of a nucleotide sequence of the transcribed region of a CYP51 gene. Preferably the mixtures comprise at least one RNA in a fungicidally effective amount.

[0113] The RNA, preferably dsRNA, molecules of the present invention are capable of inhibiting the expression of CYP51 gene(s) of the phytopathogenic fungus from which the CYP51 gene(s) defining the nucleotide sequences of the RNA molecule originate(s). The inhibition of CYP51 gene expression by dsRNA molecules of the present invention becomes detectable on the level of mRNA, on the level of polypeptide or both. For example, the change in the mRNA level of a CYP51 gene can be assessed by quantitative real-time PCR (qRTPCR) or Northern Blot.

[0114] The RNA useful in the fungicidal mixtures can be sense single-stranded RNA (ssRNA), antisense single-stranded (ssRNA), or double-stranded RNA (dsRNA). Some embodiments use a mixture of RNAs of at least two of these types. In one embodiment a double-stranded DNA / RNA hybrid is used. The RNA can include components other than standard ribonucleotides, e.g., an embodiment is an RNA that comprises terminal deoxyribonucleotides.

[0115] According to a preferred embodiment, each sense sequence is located on a different RNA strand of the dsRNA molecule than its substantially complementary antisense sequence. Thus, the sense and antisense sequences can be located on two or more than two separate strands of the dsRNA molecule. Upon hybridization of the substantially complementary sequences the strands are joined through base pairing to form one or more than one region of double-stranded RNA. The sense sequences can be on separate strands of the dsRNA molecule. According to a particular embodiment, the substantially complementary sense and antisense sequences of the dsRNA molecule of the invention are located on two separate substantially complementary strands of the dsRNA molecule.

[0116] Alternatively, the substantially complementary sense and antisense sequences of the dsRNA molecule of the invention are located on a single strand of the dsRNA molecule. The substantially complementary sequences are arranged on the RNA single strand in a manner that upon their hybridization the strand is looped back on itself through base pairing to form one or more than one panhandle or hairpin structure. A panhandle or hairpin structure consists of a double-stranded stem formed by hybridization of a first polynucleotide segment with a second polynucleotide segment, and a singled-stranded loop linking the two segments.

[0117] Embodiments include, for example, synthetic RNAs consisting wholly of ribonucleotides or mainly of ribonucleotides but with one or more terminal deoxyribonucleotides or one or more terminal dideoxyribonucleotides. In certain embodiments, the RNA comprises non-canonical nucleotides such as inosine, thiouridine, or pseudouridine.

[0118] In some embodiments the dsRNA molecule is stabilized against unwanted chemical and enzymatic degradation by reducing the dissociation of double-stranded RNA into singlestranded, non-hybridized RNA. To this end, the two hybridizing ribonucleotide sequences or regions adjacent to them can be chemically linked to each other as described, e.g., in US2008 / 0171861 A 1. Chemical linkage groups suitable for stabilizing regions of double stranded RNA include, but are not limited to, purine analogs replacing purines and branched nucleotide analogs replacing nucleotides. The dsRNA molecule can also be stabilized against unwanted enzymatic degradation by ribonucleotide modifications. Suitable ribonucleotide modifications include the replacement of the 2'-hydroxyl group of one or more than one ribonucleotide by, preferably, a 2'-amino or 2'-methyl group; and the replacement of one or more than one ribonucleotide by the same number of corresponding locked nucleotides, wherein the sugar ring is chemically modified, preferably by a 2'-0 4'-C methylene bridge.

[0119] Particular embodiments of the invention regarding the chemical or biological fungicide: The mixtures of the invention comprise at least one RNA comprising at least 18, 19, 20, 21 , 25, 50, 100, 150, 200, 250, 300, 350, 400, 450, or 500 contiguous nucleotides forming a nucleotide sequence having at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with a segment of a nucleotide sequence of the transcribed region of a CYP51 gene, or the reverse complement nucleotide sequence thereof, and at least one chemical or biological fungicide.

[0120] The following list of chemical and biological fungicides, in conjunction with which the RNAs, in particular the RNAs described in embodiments 1 to 20, can be used, is intended to illustrate the possible combinations but does not limit them: A) Respiration inhibitors inhibitors of complex III at Qosite (Qol, C3, FRAC convention; www.frac.info): azoxystrobin (A.1.1), coumethoxystrobin (A.1.2), coumoxystrobin (A.1.3), dimoxystrobin (A.1.4), enestroburin (A.1.5), fenaminstrobin (A.1.6), fenoxystrobin / flufenoxystrobin (A.1.7), fluoxastrobin (A.1.8), kresoxim-methyl (A.1.9), mandestrobin (A.1.10), metominostrobin (A.1.11), orysastrobin (A.1.12), picoxystrobin (A.1.13), pyraclostrobin (A.1.14), pyrametostrobin (A.1.15), pyraoxystrobin (A.1.16), trifloxystrobin (A.1.17), 2-(2-(3-(2,6-di- chlorophenyl)-1-methyl-allylideneaminooxymethyl)-phenyl)-2-methoxyimino- / \ / -methyl- acetamide (A.1.18), pyribencarb (A.1.19), triclopyricarb / chlorodincarb (A.1.20), famoxadone (A.1.21), fenamidone (A.1.21), methyl- / V-[2-[(1,4-dimethyl-5-phenyl-pyrazol-3- yl)oxylmethyl]phenyl]- / V-methoxy-carbamate (A.1.22), metyltetraprole (A.1.25; member of MoA subgroup A), (Z,2E)-5-[1-(2,4-dichlorophenyl)pyrazol-3-yl]-oxy-2-methoxyimino- / V,3- dimethyl-pent-3-enamide (A.1.34), (Z,2E)-5-[1-(4-chlorophenyl)pyrazol-3-yl]oxy-2- methoxyimino- / V,3-dimethyl-pent-3-enamide (A.1.35), pyriminostrobin (A.1.36), bifujunzhi (A.1.37), 2-(ortho-((2,5-dimethylphenyl-oxymethylen)phenyl)-3-methoxy-acrylic acid methylester (A.1.38);

[0121] - inhibitors of complex III at Qi site (Qil, C4): cyazofamid (A.2.1), amisulbrom (A.2.2), [(6S,7R,8R)-8-benzyl-3-[(3-hydroxy-4-methoxy-pyridine-2-carbonyl)amino]-6-methyl-4,9-di- oxo-1 , 5-dioxonan-7-yl] 2-methylpropanoate (A.2.3), fenpicoxamid (A.2.4), florylpicoxamid (A.2.5), metarylpicoxamid (A.2.6); - inhibitors of complex II (SDHI, C2): benodanil (A.3.1), benzovindiflupyr (A.3.2), bixafen (A.3.3), boscalid (A.3.4), carboxin (A.3.5), fenfuram (A.3.6), fluopyram (A.3.7), flutolanil

[0122] (A.3.8), fluxapyroxad (A.3.9), furametpyr (A.3.10), isofetamid (A.3.11), isopyrazam (A.3.12), mepronil (A.3.13), oxycarboxin (A.3.14), penflufen (A.3.15), penthiopyrad (A.3.16), pydiflumetofen (A.3.17), pyraziflumid (A.3.18), sedaxane (A.3.19), tecloftalam (A.3.20), thifluzamide (A.3.21), inpyrfluxam (A.3.22), pyrapropoyne (A.3.23), fluindapyr (A.3.28), N-[2- [2-chloro-4-(trifluoromethyl)phenoxy]phenyl]-3-(difluoromethyl)-5-fluoro-1-methyl-pyrazole-4- carboxamide (A.3.29), methyl (E)-2-[2-[(5-cyano-2-methyl-phenoxy)methyl]phenyl]-3- methoxy-prop-2-enoate (A.3.30), isoflucypram (A.3.31), 2-(difluoromethyl)- / V-(1 ,1 ,3-trimethyl- indan-4-yl)pyridine-3-carboxamide (A.3.32), 2-(difluoromethyl)- / V-[(3R)-1 , 1 ,3-trimethylindan- 4-yl]pyridine-3-carboxamide (A.3.33), 2-(difluoromethyl)- / V-(3-ethyl-1 ,1-dimethyl-indan-4-yl)- pyridine-3-carboxamide (A.3.34), 2-(difluoromethyl)- / V-[(3R)-3-ethyl-1 ,1-dimethyl-indan-4-yl]- pyridine-3-carboxamide (A.3.35), 2-(difluoromethyl)- / V-(1 ,1-dimethyl-3-propyl-indan-4-yl)py- ridine-3-carboxamide (A.3.36), 2-(difluoromethyl)- / V-[(3R)-1 ,1-dimethyl-3-propyl-indan-4-yl]- pyridine-3-carboxamide (A.3.37), 2-(difluoromethyl)- / V-(3-isobutyl-1 ,1-dimethyl-indan-4-yl)- pyridine-3-carboxamide (A.3.38), 2-(difluoromethyl)- / V-[(3 / ?)-3-isobutyl-1 ,1-dimethyl-indan- 4-yl]pyridine-3-carboxamide (A.3.39) cyclobutrifluram (A.3.24);

[0123] - other respiration inhibitors: diflumetorim (A.4.1); nitrophenyl derivates: binapacryl (A.4.2), dinobuton (A.4.3), dinocap (A.4.4), fluazinam (A.4.5), meptyldinocap (A.4.6), ferimzone (A.4.7); organometal compounds: fentin salts, e.g. fentin-acetate (A.4.8), fentin chloride (A.4.9) or fentin hydroxide (A.4.10); silthiofam (A.4.11);

[0124] - quinone outside inhibitor stigmatellin binding type (QoSI; C8): ametoctradin (A.5.1);

[0125] B) Sterol biosynthesis inhibitors (SBI fungicides)

[0126] - C14 demethylase inhibitors (DMI, G1): triazoles: azaconazole (B.1.1), bitertanol (B.1.2), bromuconazole (B.1.3), cyproconazole (B.1.4), difenoconazole (B.1.5), diniconazole (B.1.6), diniconazole-M (B.1.7), epoxiconazole (B.1.8), fenbuconazole (B.1.9), fluquinconazole (B.1.10), flusilazole (B.1.11), flutriafol (B.1.12), hexaconazole (B.1.13), imibenconazole (B.1.14), ipconazole (B.1.15), metconazole (B.1.17), myclobutanil (B.1.18), oxpoconazole (B.1.19), paclobutrazole (B.1.20), penconazole (B.1.21), propiconazole (B.1.22), prothio- conazole (B.1.23), simeconazole (B.1.24), tebuconazole (B.1.25), tetraconazole (B.1.26), triadimefon (B.1.27), triadimenol (B.1.28), triticonazole (B.1.29), uniconazole (B.1.30), 2-(2,4-difluorophenyl)-1 ,1-difluoro-3-(tetrazol-1-yl)-1-[5-[4-(2,2,2-trifluoroethoxy)phenyl]- 2-pyridyl]propan-2-ol (B.1.31), 2-(2,4-difluorophenyl)-1 ,1-difluoro-3-(tetrazol-1-yl)-1-[5-[4-(tri- fluoromethoxy)phenyl]-2-pyridyl]propan-2-ol (B.1.32), fluoxytioconazole (B.1.33), ipfen- trifluconazole (B.1.37), mefentrifluconazole (B.1.38), (2R)-2-[4-(4-chlorophenoxy)-2-(trifluoro- methyl)phenyl]-1-(1 ,2,4-triazol-1-yl)propan-2-ol, (2S)-2-[4-(4-chlorophenoxy)-2-(trifluorometh- yl)phenyl]-1-(1 ,2,4-triazol-1-yl)propan-2-ol, 2-(chloromethyl)-2-methyl-5-(p-tolylmethyl)- 1-(1 ,2,4-triazol-1-ylmethyl)cyclopentanol (B.1.43); imidazoles: imazalil (B.1.44), pefurazoate (B.1.45), prochloraz (B.1.46), triflumizol (B.1.47); pyrimidines, pyridines, piperazines: fena- rimol (B.1.49), pyrifenox (B.1.50), triforine (B.1.51), [3-(4-chloro-2-fluoro-phenyl)-5-(2,4-diflu- orophenyl)isoxazol-4-yl]-(3-pyridyl)methanol (B.1.52), 4-[[6-[2-(2,4-difluorophenyl)-1 , 1-diflu- oro-2-hydroxy-3-(1 ,2,4-triazol-1-yl)propyl]-3-pyridyl]oxy]benzonitrile (B.1.53), 2-[6-(4-bromo- phenoxy)-2-(trifluoromethyl)-3-pyridyl]-1-(1 ,2,4-triazol-1-yl)propan-2-ol (B.1.54), 2-[6-(4-chlo- rophenoxy)-2-(trifluoromethyl)-3-pyridyl]-1-(1 ,2,4-triazol-1-yl)propan-2-ol (B.1.55), methyl 2- [2-chloro-4-(4-chlorophenoxy)phenyl]-2-hydroxy-3-(1,2,4-triazol-1-yl)propanoate (B.1.56), methyl 2-[2-chloro-4-(4-chlorophenoxy)phenyl]-2-hydroxy-3-(1,2,4-triazol-1-yl)propanoic acid (B.1.57);

[0127] - delta 14-reductase inhibitors (G2): aldimorph (B.2.1), dodemorph (B.2.2), dodemorph-acetate (B.2.3), fenpropimorph (B.2.4), tridemorph (B.2.5), fenpropidin (B.2.6), piperalin (B.2.7), spiroxamine (B.2.8);

[0128] - inhibitors of 3-keto reductase: fenhexamid (B.3.1), fenpyrazamine (B.3.2);

[0129] - other sterol biosynthesis inhibitors: chlorphenomizole (B.4.1);

[0130] C) Nucleic acid synthesis inhibitors

[0131] - RNA polymerase I inhibitors (A1): benalaxyl (C.1.1), benalaxyl-M (C.1.2), kiralaxyl (C.1.3), metalaxyl (C.1.4), metalaxyl-M (C.1.5), ofurace (C.1.6), oxadixyl (C.1.7);

[0132] - other nucleic acid synthesis inhibitors (A2 to A5): hymexazole (C.2.1), octhilinone (C.2.2), oxolinic acid (C.2.3), bupirimate (C.2.4), 5-fluorocytosine (C.2.5), 5-fluoro-2-(p-tolylmethoxy)- pyrimidin-4-amine (C.2.6), 5-fluoro-2-(4-fluorophenylmethoxy)pyrimidin-4-amine (C.2.7), 5-fluoro-2-(4-chlorophenylmethoxy)pyrimidin-4 amine (C.2.8); DHODH inhibitors: ipflufenoquin (C.2.9), quinofumelin (C.2.10);

[0133] D) Inhibitors of cell division and cytoskeleton

[0134] - tubulin polymerization inhibitors (MBC, B1): benomyl (D.1.1), carbendazim (D.1.2), fuberidazole (D1.3), thiabendazole (D.1.4), thiophanate-methyl (D.1.5), pyridachlometyl (D.1.6), / \ / -ethyl-2-[(3-ethynyl-8-methyl-6-quinolyl)oxy]butanamide (D.1.8), / \ / -ethyl-2-[(3-eth- ynyl-8-methyl-6-quinolyl)oxy]-2-methylsulfanyl-acetamide (D.1.9), 2-[(3-ethynyl-8-methyl-6- quinolyl)oxy]- / V-(2-fluoroethyl)butanamide (D.1.10), 2-[(3-ethynyl-8-methyl-6-quinolyl)oxy]- / V-(2-fluoroethyl)-2-methoxy-acetamide (D.1.11), 2-[(3-ethynyl-8-methyl-6-quinolyl)oxy]- / V-propyl-butanamide (D.1.12), 2-[(3-ethynyl-8-methyl-6-quinolyl)oxy]-2-methoxy- / \ / -propyl- acetamide (D.1.13), 2-[(3-ethynyl-8-methyl-6-quinolyl)oxy]-2-methylsulfanyl- / \ / -propyl- acetamide (D.1.14), 2-[(3-ethynyl-8-methyl-6-quinolyl)oxy]- / \ / -(2-fluoroethyl)-2-methylsulfanyl- acetamide (D.1.15), 4-(2-bromo-4-fluoro-phenyl)- / V-(2-chloro-6-fluoro-phenyl)-2,5-dimethyl- pyrazol-3-amine (D.1.16);

[0135] - other cell division inhibitors (B2 to B7): diethofencarb (D.2.1), ethaboxam (D.2.2), pencycuron (D.2.3), fluopicolide (D.2.4), zoxamide (D.2.5), metrafenone (D.2.6), pyriofenone (D.2.7), phenamacril (D.2.8); fluopimomide (D.2.9);

[0136] E) Inhibitors of amino acid and protein synthesis - methionine synthesis inhibitors (D1): cyprodinil (E.1.1), mepanipyrim (E.1.2), pyrimethanil (E.1.3);

[0137] - protein synthesis inhibitors (D2 to D5): blasticidin-S (E.2.1), kasugamycin (E.2.2), kasugamycin hydrochloride-hydrate (E.2.3), mildiomycin (E.2.4), streptomycin (E.2.5), oxytetracyclin (E.2.6);

[0138] F) Signal transduction inhibitors

[0139] - MAP / histidine kinase inhibitors (E2 and E3): iprodione (F.1.2), procymidone (F.1.3), vinclozolin (F.1.4), fludioxonil (F.1.5);

[0140] - mechanism unknown (E1): quinoxyfen (F.2.1), proquinazid (F.2.2);

[0141] G) Lipid and membrane synthesis inhibitors

[0142] - Phospholipid biosynthesis inhibitors (F2): edifenphos (G.1.1), iprobenfos (G.1.2), pyrazophos (G.1.3), isoprothiolane (G.1.4);

[0143] - lipid peroxidation (F3): dicloran (G.2.1), quintozene (G.2.2), tecnazene (G.2.3), tolclofos- methyl (G.2.4), biphenyl (G.2.5), chloroneb (G.2.6), etridiazole (G.2.7);

[0144] - compounds affecting cell membrane permeability and fatty acides (F4): propamocarb (G.4.1);

[0145] H) Inhibitors with Multi Site Action

[0146] - inorganic active substances (M01 , M02): Bordeaux mixture (H.1.1), copper (H.1.2), copper acetate (H.1.3), copper hydroxide (H.1.4), copper oxychloride (H.1.5), basic copper sulfate (H.1.6), sulfur (H.1.7);

[0147] - thio- and dithiocarbamates (M03): ferbam (H.2.1), mancozeb (H.2.2), maneb (H.2.3), metam (H.2.4), metiram (H.2.5), propineb (H.2.6), thiram (H.2.7), zineb (H.2.8), ziram (H.2.9), zinc thiazole (H.2.10);

[0148] - organochlorine compounds (M04, M05, M06, M08): anilazine (H.3.1), chlorothalonil (H.3.2), captafol (H.3.3), captan (H.3.4), folpet (H.3.5), dichlofluanid (H.3.6), dichlorophen (H.3.7), hexachlorobenzene (H.3.8), pentachlorphenole (H.3.9) and its salts, phthalide (H.3.10), tolylfluanid (H.3.11);

[0149] - guanidines and others (M07, M09, M10 ;M11 , M12): guanidine (H.4.1), dodine (H.4.2), dodine free base (H.4.3), guazatine (H.4.4), gu azatine- acetate (H.4.5), iminoctadine (H.4.6), iminoctadine-triacetate (H.4.7), iminoctadine-tris(albesilate) (H.4.8), dithianon (H.4.9), 2,6- dimethyl-1 / 7,5 / 7-[1 ,4]dithiino[2,3-c:5,6-c']dipyrrole-1 ,3,5,7(2 / 7,6 / 7)-tetraone (H.4.10), fluoroimide (H.4.11), methasulfocarb (H.4.12), chinomethionat (H.4.13);

[0150] I) Cell wall synthesis inhibitors

[0151] - inhibitors of glucan synthesis: validamycin (1.1.1); chitin synthase inhibitors (H4): polyoxin B (1.1.2);

[0152] - melanin synthesis inhibitors (11 to I3): trihydroxynaphthalene reductase inhibitors (MBI-R; 11) pyroquilon (1.2.1), tricyclazole (1.2.2); dehydratase inhibitors (MBI-D, I2); carpropamid (1.2.3), dicyclomet (1.2.4), fenoxanil (1.2.5); polyketide synthase inhibitors (MBI-P, I3): tolprocarb (1.2.6);

[0153] - cellulose synthase inhibitors (H5): dimethomorph (1.3.1), flumorph (1.3.2), mandipropamid (1.3.3), pyrimorph (1.3.4), benthiavalicarb (1.3.5), iprovalicarb (1.3.6), valifenalate (1.3.7);

[0154] J) Plant defence inducers (P1 to P8)

[0155] - acibenzolar-S-methyl (J.1.1), probenazole (J.1.2), isotianil (J.1.3), tiadinil (J.1.4), prohexa- dione-calcium (J.1.5); phosphonates: fosetyl (J.1.6), fosetyl-aluminum (J.1.7), phosphorous acid and its salts (J.1.8), potassium or sodium bicarbonate (J.1.9), 4-cyclopropyl- / V-(2,4-dhmethoxy-,phenyl)thiadiazole-5-carboxamide (J.1.10), calcium phosphonate

[0156] (J.1.11), potassium phosphonate (J.1.12), dichlobentiazox (J.1.13);

[0157] K) Unknown mode of action (U, Unknown)

[0158] - bronopol (K.1.1), cyflufenamid (K.1.3), cymoxanil (K.1.4), dazomet (K.1.5), debacarb (K.1.6), diclomezine (K.1.8), difenzoquat (K.1.9), difenzoquat-methylsulfate (K.1.10), diphenylamin (K.1.11), fenitropan (K.1.12), flumetover (K.1.14), flumetylsulforim (K.1.60), flusulfamide

[0159] (K.1.15), flutianil (K.1.16), harpin (K.1.17), nitrapyrin (K.1.19), nitrothal-isopropyl (K.1.20), oxin-copper (K.1.22), seboctylamine (K.1.61), tebufloquin (K.1.24), tecloftalam (K.1.25), triazoxide (K.1.26), / V -(4-(4-chloro-3-trifluoromethyl-phenoxy)-2,5-dimethyl-phenyl)- / \ / -ethyl- / V-methyl formamidine (K.1.27), / V-(4-(4-fluoro-3-trifluoromethyl-phenoxy)-2,5-dimethyl- phenyl)- / V-ethyl- / \ / -methyl formamidine (K.1.28), / \ / -[4-[[3-[(4-chlorophenyl)methyl]-1,2,4- thiadiazol-5-yl]oxy]-2,5-dimethyl-phenyl]- / V-ethyl- / V-methyl-formamidine (K.1.29), / \ / ’-(5- bromo-6-indan-2-yloxy-2-methyl-3-pyridyl)- / V-ethyl- / \ / -methyl-formamidine (K.1.30), / \ / ’-[5- bromo-6-[1-(3,5-difluorophenyl)ethoxy]-2-methyl-3-pyridyl]- / \ / -ethyl- / \ / -methyl-formamidine (K.1.31), / V-[5-bromo-6-(4-isopropylcyclohexoxy)-2-methyl-3-pyridyl]- / \ / -ethyl- / \ / -methyl- formamidine (K.1.32), / V-[5-bromo-2-methyl-6-(1-phenylethoxy)-3-pyridyl]- / \ / -ethyl- / \ / -methyl- formamidine (K.1.33), / V -(2-methyl-5-trifluoromethyl-4-(3-trimethylsilanyl-propoxy)-phenyl)- / V-ethyl-ZV-methyl formamidine (K.1.34), / V-(5-difluoromethyl-2-methyl-4-(3-trimethylsilanyl- propoxy)-phenyl)- / V-ethyl- / \ / -methyl formamidine (K.1.35), 2-(4-chloro-phenyl)- / V-[4-(3,4- dimethoxy-phenyl)-isoxazol-5-yl]-2-prop-2-ynyloxy-acetamide (K.1.36), 3-[5-(4-chloro- phenyl)-2,3-dimethyl-isoxazolidin-3-yl]-pyridine (pyrisoxazole) (K.1.37), 3-[5-(4- methylphenyl)-2,3-dimethyl-isoxazolidin-3-yl]-pyridine (K.1.38), 5-chloro-1-(4,6-dimethoxy- pyrimidin-2-yl)-2-methyl-1 / - / -benzoimidazole (K.1.39), ethyl (Z)-3-amino-2-cyano-3-phenyl- prop-2-enoate (K.1.40), picarbutrazox (K.1.41), pentyl / \ / -[6-[[(Z)-[(1-methyltetrazol-5-yl)- phenyl-methylene]amino]oxymethyl]-2-pyridyl]carbamate (K.1.42), but-3-ynyl / \ / -[6-[[(Z)-[(1- methyltetrazol-5-yl)-phenyl-methylene]amino]oxymethyl]-2-pyridyl]carbamate (K.1.43), benziothiazolinone (K.1.48), bromothalonil (K.1.49), 2-(6-benzyl-2-pyridyl)quinazoline (K.1.50), 2-[6-(3-fluoro-4-methoxy-phenyl)-5-methyl-2-pyridyl]quinazoline (K.1.51), / -(2,5- dimethyl-4-phenoxy-phenyl)- / V-ethyl- / V-methyl-formamidine (K.1.53), aminopyrifen (K.1.54), / V'-[5-bromo-2-methyl-6-(1-methyl-2-propoxy-ethoxy)-3-pyridyl]- / \ / -ethyl- / \ / -methyl- formamidine (K.1.56), / V-[4-(4,5-dichlorothiazol-2-yl)oxy-2,5-dimethyl-phenyl]- / V-ethyl- / V- methyl-formamidine (K.1.57), flufenoxadiazam (K.1.58) [MoA proposed: class II histone deacetylase inhibitor], / V-methyl-4-[5-(trifluoromethyl)-1 ,2,4-oxadiazol-3- yl]benzenecarbothioamide (K.1.59), / V-methoxy- / V-[[4-[5-(trifluoromethyl)-1 ,2,4-oxadiazol-3- yl]phenyl]methyl]cyclopropanecarboxamide (K.1.60; WO2018 / 177894, WO 2020 / 212513), / V-((4-[5-(trifluoromethyl)-1 ,2,4-oxadiazol-3-yl]phenyl)methyl)propanamide (K.1.62), 3,3,3- trifluoro- / V-[[3-fluoro-4-[5-(trifluoromethyl)-1 ,2,4-oxadiazol-3-yl]phenyl]methyl]propanamide (K.1.63), 3,3,3-trifluoro- / V-[[2-fluoro-4-[5-(trifluoromethyl)-1 ,2,4-oxadiazol-3- yl]phenyl]methyl]propanamide (K.1.64), / V-[2,3-difluoro-4-[5-(trifluoromethyl)-1 ,2,4-oxadiazol- 3-yl]benzyl]butanamide (K.1.65), / V-[[2,3-difluoro-4-[5-(trifluoromethyl)-1 ,2,4-oxadiazol-3- yl]phenyl]methyl]-3,3,3-trifluoro-propanamide (K.1.66), 1 -methoxy- 1 -methyl-3-[[4-[5- (trifluoromethyl)-1 ,2,4-oxadiazol-3-yl]phenyl]methyl]urea (K.1.67), 1 , 1 -diethyl-3-[[4-[5- [trifluoromethyl]-1 ,2,4-oxadiazol-3-yl]phenyl]methyl]urea (K.1 .68), / V,2-dimethoxy- / V-[[4-[5- (trifluoromethyl)-l ,2,4-oxadiazol-3-yl]phenyl]methyl]propanamide (K.1.69), / V-ethyl-2-methyl- / V-[[4-[5-(trifluoromethyl)-1 ,2,4-oxadiazol-3-yl]phenyl]methyl]propanamide (K.1.70), 1- methoxy-3-methyl-1-[[4-[5-(trifluoromethyl)-1 ,2,4-oxadiazol-3-yl]phenyl]methyl]urea (K.1.71),

[0160] 1-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]pyrrolidin-2-one (K.1.72), 1-[[4- [5-(trifluoromethyl)-1 ,2,4-oxadiazol-3-yl]phenyl]methyl]piperidin-2-one (K.1.73), 4-[[4-[5- (trifluoromethyl)-l ,2,4-oxadiazol-3-yl]phenyl]methyl]morpholin-3-one (K.1.74), 4,4-dimethyl-

[0161] 2-[[4-[5-(trifluoromethyl)-1 ,2,4-oxadiazol-3-yl]phenyl]methyl]isoxazolidin-3-one (K.1.75), 2-[[4- [5-(trifluoromethyl)-1 ,2,4-oxadiazol-3-yl]phenyl]methyl]isoxazolidin-3-one (K.1.76), 5,5- dimethyl-2-[[4-[5-(trifluoromethyl)-1 ,2,4-oxadiazol-3-yl]phenyl]methyl]isoxazolidin-3-one (K.1.77), 3,3-dimethyl-1-[[4-[5-(trifluoromethyl)-1 ,2,4-oxadiazol-3-yl]phenyl]methyl]piperidin- 2-one (K.1.78), 2-[[4-[5-(trifluoromethyl)-1 ,2,4-oxadiazol-3-yl]phenyl]methyl]oxazinan-3-one (K.1.79), 1-[[3-fluoro-4-[5-(trifluoromethyl)-1 ,2,4-oxadiazol-3-yl]phenyl]methyl]azepan-2-one (K.1.80), 4,4-dimethyl-1-[[4-[5-(trifluoromethyl)-1 ,2,4-oxadiazol-3-yl]phenyl]methyl]pyrrolidin-

[0162] 2-one (K.1.81), 5-methyl-1-[[4-[5-(trifluoromethyl)-1 ,2,4-oxadiazol-

[0163] 3-yl]phenyl]methyl]pyrrolidin-2-one (K.1.82), ethyl 1-[[4-[5-(trifluoromethyl)-1 ,2,4-oxadiazol-

[0164] 3-yl]phenyl]methyl]pyrazole-4-carboxylate (K.1 .83), / V-methyl-1-[[4-[5-(trifluoromethyl)-

[0165] 1 .2.4-oxadiazol-3-yl]phenyl]methyl]pyrazole-4-carboxamide (K.1 .84), / V, / V-dimethyl- 1-[4-[5-(trifluoromethyl)-1 ,2,4-oxadiazol-3-yl]benzyl]-1 H-1 ,2,4-triazol-3-amine (K.1.85), / V-methoxy- / V-methyl-1-[[4-[5-(trifluoromethyl)-1 ,2,4-oxadiazol-3-yl]phenyl]methyl]pyrazole-

[0166] 4-carboxamide (K.1.86), propyl-1-[[4-[5-(trifluoromethyl)-1 ,2,4-oxadiazol-3-yl]phenyl]methyl]- pyrazole-4-carboxamide (K.1.87), / V-methoxy-1-[[4-[5-(trifluoromethyl)-1 ,2,4-oxadiazol- 3-yl]phenyl]methyl]pyrazole-4-carboxamide (K.1.88), / V-al lyl- / V-[[4-[5-(trifl uoromethy I)-

[0167] 1.2.4-oxadiazol-3-yl]phenyl]methyl]propanamide (K.1.89), 3-ethyl-1-methoxy-1-[[4-[5-(tri- fluoromethyl)-1 ,2,4-oxadiazol-3-yl]phenyl]methyl]urea (K.1.90), 1 ,3-dimethoxy-1-[[4-[5-(tri- fluoromethyl)-1 ,2,4-oxadiazol-3-yl]phenyl]methyl]urea (K.1.91), A / -allyl- / \ / -[[4-[5-(trifluoro- methyl)-1 ,2,4-oxadiazol-3-yl]phenyl]methyl]acetamide (K.1.92), / V-[4-[5-(trifluoromethyl)- 1 ,2,4-oxadiazol-3-yl]benzyl]cyclopropanecarboxamide (K.1.93), 1-methyl-3-[[4-[5-(trifluoro- methyl)-1 ,2,4-oxadiazol-3-yl]phenyl]methyl]urea (K.1.94), / \ / '-[2-chloro-4-(2-fluorophenoxy)- 5-methyl-phenyl]- / V-ethyl- / V-methyl-formamidine (K.1.95), / V'-[2-chloro-4-[(4-methoxy- phenyl)methyl]-5-methyl-phenyl]- / \ / -ethyl- / \ / -methyl-formamidine (K.1 .96), / \ / '-[2-chloro-4-[(4- cyano-phenyl)methyl]-5-methyl-phenyl]- / V-ethyl- / V-methyl-formamidine (K.1 .97), A / -[2,5- dimethyl-4-(o-tolylmethyl)phenyl]- / \ / -ethyl-N-methyl-formamidine (K.1.98), 6-chloro-3-(3- cyclopropyl-2-fluoro-phenoxy)- / V-[2-(2,4-dimethylphenyl)-2,2-difluoro-ethyl]-5-methyl-pyri- dazine-4-carboxamide (K.1.99), 3-(3-bromo-2-fluoro-phenoxy)-6-chloro- / V-[2-(2-chloro-

[0168] 4-methyl-phenyl)-2,2-difluoro-ethyl]-5-methyl-pyridazine-4-carboxamide (K.1.100), 6-chloro- / \ / -[2-(2-chloro-4-methyl-phenyl)-2,2-difluoro-ethyl]-3-(3-cyclopropyl-2-fluoro-phenoxy)-

[0169] 5-methyl-pyridazine-4-carboxamide (K.1 .101), 6-chloro-3-(3-cyclopropyl-2-fluoro-phenoxy)- / V-[2-(3,4-dimethylphenyl)-2,2-difluoro-ethyl]-5-methyl-pyridazine-4-carboxamide (K.1.102),

[0170] 6-chloro-3-(3-chloro-2-fluoro-phenoxy)- / V-[2-(2,4-dimethylphenyl)-2,2-difluoro-ethyl]-5-meth- yl-pyridazine-4-carboxamide (K.1.103), / \ / -[2-(2-bromo-4-methyl-phenyl)-2,2-difluoro-ethyl]-

[0171] 6-chloro-3-(3-cyclopropyl-2-fluoro-phenoxy)-5-methyl-pyridazine-4-carboxamide (K.1.104);

[0172] L) Biopesticides

[0173] L1) Microbial pesticides with fungicidal, bactericidal, viricidal and / or plant defense activator activity: Ampelomyces quisqualis, Aspergillus flavus, Aureobasidium pullulans, Bacillus altitudinis, B. amyloliquefaciens, B. amyloliquefaciens ssp. plantarum (also referred to as B. velezensis), B. megaterium, B. mojavensis, B. mycoides, B. pumilus, B. simplex, B. solisalsi, B. subtilis, B. subtilis var. amyloliquefaciens, B. velezensis, Candida oleo- phila, C. saitoana, Clavibacter michiganensis (bacteriophages), Coniothyrium minitans, Cryphonectria parasitica, Cryptococcus albidus, Dilophosphora alopecuri, Fusarium oxysporum, Clonostachys rosea f. catenulate (also named Gliocladium catenulatum), Gliocladium roseum, Lysobacter antibioticus, L. enzymogenes, Metschnikowia fructi- cola, Microdochium dimerum, Microsphaeropsis ochracea, Muscodor albus, Paeni- bacillus alvei, Paenibacillus epiphyticus, P. polymyxa, Pantoea vagans, Penicillium bilaiae, Phlebiopsis gigantea, Pseudomonas sp., Pseudomonas chloraphis, Pseudo- zyma flocculosa, Pichia anomala, Pythium oligandrum, Sphaerodes mycoparasitica, Streptomyces griseoviridis, S. lydicus, S. violaceusniger, Talaromyces flavus, Tricho- derma asperelloides, T. asperellum, T. atroviride, T. fertile, T. gamsii, T. harmatum, T. harzianum, T. polysporum, T. stromaticum, T. virens, T. viride, Typhula phacorrhiza, Ulocladium oudemansii, Verticillium dahlia, zucchini yellow mosaic virus (avirulent strain);

[0174] L2) Biochemical pesticides with fungicidal, bactericidal, viricidal and / or plant defense activator activity: harpin protein, Reynoutria sachalinensis extract, Melaleuca alternifolia extract;

[0175] L3) Natural compounds with membrane disturbing activity: limonene, terpinene, pinene, p- cymene, eugenol, geraniol, thymol, carvacrol, cinnamaldehyde, benzaldehyde, vanillin, anisaldehyde, syringaldehyde, cuminaldehyde, salicylaldehyde, citral, natamycin, fusaricidine, fengycin, iturin, surfactin, metal salts of C12 to C24 fatty acids, preferably metal salts of oleate, like potassium oleate.

[0176] The microbial pesticides, embrace not only the isolated, pure cultures of the respective microorganism as defined herein, but also its cell-free extract, its suspension in a whole broth culture and a metabolite-containing culture medium or a purified metabolite obtained from a whole broth culture of the microorganism. Many of these biopesticides have been deposited under deposition numbers mentioned herein (the prefices such as ATCC or DSM refer to the acronym of the respective culture collection, for details see e.g. here: http: / / www. wfcc.info / ccinfo / collection / by acronym / ), are referred to in literature, registered and / or are commercially available:

[0177] Bacillus amyloliquefaciens strain AP-188 (NRRL B-50615 and B-50331 ; US 8,445,255); B. amyloliquefaciens ssp. plantarum strains formerly also sometimes referred to as B. subtilis, recently together with B. methylotrophicus, and B. velezensis classified as B. velezensis (I nt. J. Syst. Evol. Microbiol. 66, 1212-1217, 2016): B. a. ssp. plantarum or B. velezensis D747 isolated from air in Kikugawa-shi, Japan (US 20130236522 A1 ; FERM BP-8234; e.g. Double Nickel™ 55 WDG from Certis LLC, USA), B. a. ssp. plantarum or B. velezensis FZB24 isolated from soil in Brandenburg, Germany (also called SB3615; DSM 96-2; J. Plant Dis. Prot. 105, 181-197, 1998; e.g. TaegroO from Novozyme Biologicals, Inc., USA), B. a. ssp. plantarum or B. velezensis FZB42 isolated from soil in Brandenburg, Germany (DSM 23117; J. Plant Dis. Prot. 105, 181-197, 1998; e.g. RhizoVital® 42 from AbiTEP GmbH, Germany), B. a. ssp. plantarum or B. velezensis MBI600 isolated from faba bean in Sutton Bonington, Nottinghamshire, U.K. at least before 1988 (also called 1430; NRRL B-50595; US 2012 / 0149571 A1 ; e.g. Integral® from BASF Corp., USA), B. a. ssp. plantarum or B. velezensis QST-713 isolated from peach orchard in 1995 in California, U.S.A. (NRRL B-21661 ; e.g. Serenade® MAX from Bayer Crop Science LP, USA), B. a. ssp. plantarum or B. velezensis TJ1000 isolated in 1992 in South Dakoda, U.S.A, (also called 1 BE; ATCC BAA-390; CA 2471555 A1; e.g. QuickRoots™ from TJ Technologies, Watertown, SD, USA); B. firmus CNCM 1-1582, a variant of parental strain EIP- N1 (CNCM 1-1556) isolated from soil of central plain area of Israel (WO 2009 / 126473, US 6,406,690; e.g. Votivo® from Bayer CropScience LP, USA), B. pumilus GHA 180 isolated from apple tree rhizosphere in Mexico (IDAC 260707-01 ; e.g. PRO-MIX® BX from Premier Horticulture, Quebec, Canada), B. pumilus INR-7 otherwise referred to as BU-F22 and BU-F33 isolated at least before 1993 from cucumber infested by Erwinia tracheiphila (NRRL B-50185, NRRL B-50153; US 8,445,255), B. pumilus KFP9F isolated from the rhizosphere of grasses in South Africa at least before 2008 (NRRL B-50754; WO 2014 / 029697; e.g. BAC-UP or FUSION- P from BASF Agricultural Specialities (Pty) Ltd., South Africa), B. pumilus QST 2808 was isolated from soil collected in Pohnpei, Federated States of Micronesia, in 1998 (NRRL B-30087; e.g. Sonata® or Ballad® Plus from Bayer Crop Science LP, USA), B. simplex ABU 288 (NRRL B-50304; US 8,445,255), B. subtilis FB17 also called UD 1022 or UD10-22 isolated from red beet roots in North America (ATCC PTA-11857; System. Appl. Microbiol. 27, 372-379, 2004; US 2010 / 0260735; WO 2011 / 109395); Paenibacillus alvei NAS6G6 isolated from the rhizosphere of grasses in South Africa at least before 2008 (WO 2014 / 029697; NRRL B-50755; e.g. BAC-UP from BASF Agricultural Specialities (Pty) Ltd., South Africa), Paenibacillus strains isolated from soil samples from a variety of European locations including Germany: P. epiphyticus Lu17015 (WO 2016 / 020371 ; DSM 26971), P. polymyxa ssp. plantarum Lu16774 (WO 2016 / 020371 ; DSM 26969), P. p. ssp. plantarum strain Lu17007 (WO 2016 / 020371 ;

[0178] DSM 26970); Reynoutria sachalinensis extract (EP 0307510 B1 ; e.g. Regalia® SC from Marrone BioInnovations, Davis, CA, USA or Milsana® from BioFa AG, Germany), Trichoderma asperelloides JM41 R isolated in South Africa (NRRL 50759; also referred to as T. fertile', e.g. Trichoplus® from BASF Agricultural Specialities (Pty) Ltd., South Africa), T. harzianum -22 also called KRL-AG2 (ATCC 20847; BioControl 57, 687-696, 2012; e.g. Plantshield® from BioWorks Inc., USA or SabrEx™ from Advanced Biological Marketing Inc., Van Wert, OH, USA).

[0179] Preferred chemical and biological fungicides to be combined with at least RNA comprising at least 18, 19, 20, 21, 25, 50, 100, 150, 200, 250, 300, 350, 400, 450, or 500 contiguous nucleotides forming a nucleotide sequence having at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with a segment of a nucleotide sequence of the transcribed region of a CYP51 gene, or the reverse complement nucleotide sequence thereof, preferably at least one RNA described in embodiments 1 to 20, belong to the following classes: a. respiration inhibitors, preferably inhibitors of complex III at Qosite, inhibitors of complex II and other respiration inhibitors, more preferred inhibitors of complex III at Qosite, inhibitors of complex II, b. sterol biosynthesis inhibitors, preferably C14 demethylase inhibitors, delta14-reductase inhibitors and inhibitors of 3-keto reductase, more preferred, C14 demethylase inhibitors, c. inhibitors of cell division and cytoskeleton, preferably other cell division inhibitors d. signal transduction inhibitors, preferably the ones with unknown mechanism e. inhibitors with multi-site action, preferably inorganic active substances, f. plant defense inducers, and g. biopesticides

[0180] More preferred chemical and biological fungicides to be combined with at least RNA comprising at least 18, 19, 20, 21, 25, 50, 100, 150, 200, 250, 300, 350, 400, 450, or 500 contiguous nucleotides forming a nucleotide sequence having at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with a segment of a nucleotide sequence of the transcribed region of a CYP51 gene, or the reverse complement nucleotide sequence thereof, preferably at least one RNA described in embodiments 1 to 20, belong to the following classes: a. azoxystrobin, kresoxim-methyl, pyraclostrobin, trifloxystrobin, boscalid, pydiflumetofen and meptyldinocap, b. difenoconazole, fenbuconazole, flutriafol, myclobutanil, penconazole, tebuconazole, tetraconazole, mefentrifluconazole, spiroxamine and fenhexamide, c. metrafenone, d. proquinazid, e. copper, copper acetate, copper hydroxide, copper oxychloride, basic copper sulfate and sulfur, and f. fosetyl, fosetyl-aluminium and potassium phosphonate, and g. B. subtilis, B. subtilis var. amyloliquefaciens, B. velezensis, Reynoutria sachalinensis extract.

[0181] In some embodiments the chemical and biological fungicides are selected from at least one group selected of: a. azoxystrobin, kresoxim-methyl, pyraclostrobin, trifloxystrobin, b. boscalid, pydiflumetofen, c. meptyldinocap, d. difenoconazole, fenbuconazole, flutriafol, myclobutanil, penconazole, tebuconazole, tetraconazole, mefentrifluconazole, e. spiroxamine, f. fenhexamide, g. metrafenone, h. proquinazid, i. copper, j. sulfur, k. fosetyl, fosetyl-aluminium l. potassium phosphonate, and m. B. subtilis, B. subtilis var. amyloliquefaciens, B. velezensis, and n. Reynoutria sachalinensis extract.

[0182] Preferably the at least one chemical or biological fungicide in the mixture is present in a fungicidally effective amount. More preferred, at least one RNA and at least one chemical or biological fungicide in the mixture are present in a fungicidally effective amount. Preferably at least one RNA comprising at least 18, 19, 20, 21, 25, 50, 100, 150, 200, 250, 300, 350, 400, 450, or 500 contiguous nucleotides forming a nucleotide sequence having at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with a segment of a nucleotide sequence of the transcribed region of a CYP51 gene, or the reverse complement nucleotide sequence thereof and the at least one chemical or biological fungicide in the mixture are present in a ratio which provides a synergistic fungicidal effect, preferably a synergistic fungicidal effect against at least one of the phytopathogenic fungi selected from Erysiphe necator, Erysiphe cichoracearum, Erysiphe neolycopersici or Botrytis cinerea.

[0183] In particular preferred are mixtures comprising at least two RNAs comprising at least 18, 19, 20, 21, 25, 50, 100, 150, 200, 250, 300, 350, 400, 450, or 500 contiguous nucleotides forming a nucleotide sequence having at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with a segment of a nucleotide sequence of the transcribed region of a CYP51 gene, or the reverse complement nucleotide sequence thereof and comprising at least one biological or chemical fungicide in a ratio which provides a synergistic fungicidal effect against at least two of the phytopathogenic fungi selected from Erysiphe necator, Erysiphe cichoracearum, Erysiphe neolycopersici or Botrytis cinerea.

[0184] Preferably, such mixtures provide a synergistic fungicidal effect against at least one of the phytopathogenic fungi selected from Erysiphe necator, Erysiphe cichoracearum, Erysiphe neolycopersici and against Botrytis cinerea.

[0185] In one embodiment such mixtures provide a synergistic fungicidal effect against Erysiphe necator and against Botrytis cinerea.

[0186] Particular embodiments of the invention regarding transfer agents:

[0187] When applied to a plant or a phytopathogenic fungus, the RNAs are usually applied with a plant-compatible carrier, which has preferably the features of a transfer agent. A transfer agent can be any substance, which enables an RNA which is applied to the surface of an organism to enter its cells and thereby to cross several barriers, such as cuticular waxes, cell walls and cell membranes. Many different kinds of transfer agents have been described in the art, for example WO2011 / 112570 describes the use of sodium or lithium salts of fatty acids, organosilicone sufactants and / or abrasives, such as carborundum, corundum, sand, calcite, pumice and the like. WO2017 / 106339 describes the use of cross-linked cationic polysaccharides.

[0188] WO2016201523 and WO2015089543 describe the use of nanoclays and Layered Double Hydroxide (LDH) particles. LDH is an inorganic layered material that occurs naturally due to saline precipitation. LDH features brucite-like compounds that form positively charged layers, allowing negatively charged dsRNA to enter between the layers and be protected from washing, RNase degradation, and UV exposure. The use of carbon dots is described in Wang et al, “Functionalized Carbon Dot-Delivered RNA Nano Fungicides as Superior Tools to Control Phytophthora Pathogens through Plant RdRP1 Mediated Spray-Induced Gene Silencing”, Advanced Functional Materials, 2023, 33, 2213143. Carbon quantum dots are composed of carbon (>50% in typical carbon dots), oxygen, nitrogen, and hydrogen, in which the carbon atoms were sp2hybridized with unsaturated sp3carbon atoms. In certain embodiments the dsRNA can be attached to cellulose and its modified forms, e.g., microfibrillated cellulose, chitosan particles or encapsulated with such polymers. In certain embodiments the chitosan polymers can be allosperse. The use of Chitosan as transfer agent is for example described in Zhou et al. “Chitosan / dsRNA polyplex nanoparticles advance environmental RNA interference efficiency through activating clathrin-dependent endocytosis”, International Journal of Biological Macromolecules 253 (2023) 127021. In certain embodiments, the composition comprises RNA incorporated into a lipid or liposome,

[0189] In one embodiment at least one transfer agent is selected from organosilicone surfactants. Organosilicone compounds useful as transfer agents for use in this invention include, but are not limited to, compounds that include: (a) a trisiloxane head group that is covalently linked to, (b) an alkyl linker including, but not limited to, an n-propyl linker, that is covalently linked to, (c) a polyglycol chain, that is covalently linked to, {d) a terminal group. Trisiloxane head groups of such organosilicone compounds include, but are not limited to, heptamethyltrisiloxane. Alkyl linkers can include, but are not limited to, an n-propyl linker. Polyglycol chains include, but are not limited to, polyethylene glycol or polypropylene glycol. Polyglycoi chains can comprise a mixture that provides an average chain length "n" of about 7.5". In certain embodiments, the average chain length "n” can vary from about 5 to about 14. Terminal groups can include, but are not limited to, alkyl groups such as a methyl group. Organosilicone compounds useful as transfer agents include, but are not limited to, trisiloxane ethoxylate surfactants or polyalkylene oxide modified heptamethyl trisiloxane. An example of a transfer agent for use in this invention is SILWET L-77® brand surfactant having CAS Number 27306-78-1 and is described with the formula and currently available from Momentive Performance Materials, Aibany, N.Y. BREAK-THRU S

[0190] 240 brand a Polyether Modified Polysiloxane (CASRN Proprietary) surfactant, currently available from Goldschmidt Chemical Corporation, Hopewell, VA. BREAK-THRU S 279 an end capped polyether trisiloxane surfactant, which components are listed in the following chemical inventories: EINECS, TSCA, ENCS, AICS, EGL, PIGGS CHINA, NDSL INDUCE brand adjuvant NMFC Item 42652, Class 60, currently available from Helena Chemical Company, Collierville, TN. FRANCHISE® with LECI-TECH® brand surfactant having a CA REG No. 34704-50065, currently available from Loveland Products, Inc. Greely, CO. One embodiment includes a composition that further comprises BREAK-thru 301. When used as transfer agents, organosilicone compounds are usually used in the range of about 0.015 to about 2 percent by weight (wt percent) of the total weight of the preparation comprising the at least one RNA. Preferred ranges are in the range of about 0.3 to about 1 percent by weight (wt percent) or about 0.5 to about 1 %, by weight.

[0191] Further embodiments of transfer agents include one or more salts such as ammonium chloride, tetrabutylphosphonium bromide, and ammonium sulfate. In some embodiments, ammonium chloride, tetrabutylphosphonium bromide, and / or ammonium sulfate are used at a concentration of about 0.5% to about 5% (w / v), or about 1 % to about 3% (w / v), or about 2% (w / v). In certain embodiments, the composition including the RNA includes an ammonium salt at a concentration greater or equal to 300 millimolar. In certain embodiments, a combination of an organosilicone in a concentration of about 0.015 to about 2 percent by weight (wt percent) and an ammonium sulfate at concentrations from about 80 to about 1200 mM or about 150 mM to about 600 mM.is used.

[0192] Further transfer agents are phosphate salts such as, but not limited to, calcium, magnesium, potassium, or sodium phosphate salts. Some embodiments use sodium phosphate salt in a range of about 10 mM to about 160 mM or in a range of about 20 mM to about 40 mM. In some embodiments the pH-value of the sodium phosphate buffer is about 6.8.

[0193] Further transfer agents include surfactants and / or effective molecules contained therein. Surfactants and / or effective molecules contained therein include, but are not limited to, sodium or lithium salts of fatty acids and organosilicone surfactants. In certain embodiments, a mixture comprising RNA is formulated with counter-ions or other molecules that are known to associate with nucleic acid molecules. Non-limiting examples include, tetraalkyl ammonium ions, trialkyl ammonium ions, sulfonium ions, lithium ions, and polyamines such as polyethyleneimine, spermine, spermidine, or putrescine.

[0194] Preferably the at least one RNA comprising at least 18, 19, 20, 21 , 25, 50, 100, 150, 200, 250, 300, 350, 400, 450, or 500 contiguous nucleotides forming a nucleotide sequence having at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with a segment of a nucleotide sequence of the transcribed region of a CYP51 gene, or the reverse complement nucleotide sequence thereof, preferably at least one RNA as described in at least one of the embodiments 1 to 20, are applied in combination with a transfer agent selected from the group consisting of: organosilicone sufactants, nanoclays, Layered Double Hydroxide particles, carbon dots, cellulose, chitosan and liposomes.

[0195] Preferred organosilicone sufactants are trisiloxane ethoxylate surfactants or polyalkylene oxide modified heptamethyl trisiloxane. In one embodiment the organosilicone is SILWET L-77®. Preferred is also a combination of an organosilicone and an ammonium sulfate.

[0196] Transfer agents as well as the RNA and the fungicide can be incorporated as part of a composition and applied at the same time or one or more of the different parts can be provided separately to be combined shortly before application to the plant and / or the fungus, or the different parts can be applied prior to or following application of the RNA.

[0197] Accordingly, one embodiment of the invention is a kit of at least three parts for preparing a mixture comprising an RNA and a chemical or biological fungicide. Said kit of at least three parts comprising: a) a part comprising at least one RNA for the control of a phytopathogenic fungus as described above, and b) a part comprising at least one chemical or biological fungicide in a concentrated form, and c) a part comprising instructions how to combine part a) and part b) to prepare the mixture. A further embodiment of the invention is a kit of at least three parts for preparing a mixture comprising an RNA, a chemical or biological fungicide and at least one transfer agent. Said kit of at least three parts comprising: a) a part comprising at least one RNA for the control of a phytopathogenic fungus as described above in a concentrated form and comprising at least one chemical or biological fungicide in a concentrated form and b) a part comprising at least one transfer agent in a concentrated form, and c) a part comprising instructions how to combine part a) and part b) to prepare the mixture. The different parts of the mixture are provided in a concentrated form, which means that the respective components have a higher concentration in this form than in the final mixture. Usually, the concentrated components are diluted with a plant compatible carrier, for example, but not excluding others, water.

[0198] Particular embodiments of the invention regarding agrochemical compositions:

[0199] The mixtures of the invention can be applied directly to the plant or fungi but are preferably comprised by agrochemical compositions to enhance the physical and chemical stability of the RNAs of the mixture. The formulation type of the agrochemical compositions is usually an aqueous based concentrate in which the RNA is completely solubilized. The agrochemical compositions comprise one or more auxiliaries or co-formulants. Accordingly, one embodiment of the invention is an agrochemical composition comprising: a) at least one RNA for the control of a phytopathogenic fungus as described above b) at least one chemical or biological fungicide and c) at least one auxiliary.

[0200] The form of the agrochemical composition of the invention is expediently adapted to the desired mode of application. Suitable forms include ready-to-use compositions as well as concentrates. For example, the composition of the invention can have the form of a spray-able liquid, a dustable powder, an emulsifiable concentrate, granules (e.g. coated, encapsulated or impregnated granules), a paste, or a water-dispersable or watersoluble powder for seed treatment. Methods for preparing such compositions are known in the art. Preferred auxiliaries are metal-ion sequestrants, UV Protectants, antifreeze agents, buffer, antifoam agents, biocides and surfactants.

[0201] Metal-ion sequestrants have the ability to chelate divalent metal cations which are necessary for enzymatic activity of many common nucleases. The presence of a metal-ion sequestrant has the aim to inhibit enzymatic nuclease activity respect to dsRNA or single stranded RNA. Examples of metal-ion sequestrants may include but are not limited to citrate, ammonium sulfate, acrylic copolymer (for example NOVERITE® K-775), ethylenediaminetetraacetic acid (EDTA), lignosulfonates, sodium lignosulfonates, glutamate diacetate (GLDA), diethylenetriaminepentaacidic acid (DTPA), N-carboxymethyliminobis (ethylenenitrilo)tetra(acetic acid), Ethylenediamine-N, N'-bis(2-hydroxyphenylacetic acid), N-(2- hydroxyethyl)ethylenediamine-N, N', N'-tiacetic acid, Ethylenediamine-N, N'-bis(2-hydroxy-6- methylphenylacetic acid, EthylenediamineN, N'-bis(4-carboxy-2-hydroxyphenylacetic acid, ethylenediamine-N,N'bis(2-hydroxy-5-sulfophenylacetic acid.

[0202] UV Protectants increase the stability of single stranded or double stranded RNA when exposed to ultra-violet radiation. UV-Protectants which may be used in agrochemical compositions have for example been described in WO2010115720 and WO2010115721. Some embodiments use polymeric surfactants containing conjugated aromatic functionalities, exemplified by lignin; naphthalene-based surfactants, such as lignosulfonates; dioctyl sodium sulfosuccinates; and naphthalene sulfanate condensates.

[0203] Antifreeze agents refer to auxiliaries which lowers the freezing point of a water-based liquid. Examples of antifreeze agents may include but are not limited to propylene glycol, methanol, ethanol, propanol, isopropanol, alkylene glycol ethers, alkylene glycol alkyl ethers, and glycerols,

[0204] Buffers are used to stabilize the agrochemical composition against pH changes due to the addition of acidic or basic components. Several buffers are known in the art. Non-limiting examples of buffers include: potassium phosphate, BisTris (bis-tris methane), ADA (2-[(2- amino-2-oxoethyl)-(carboxymethyl)amino]aceticacid), ACES (2- (carbamoylmethylamino)ethanesulfonic acid), PIPES (1 ,4-Piperazinediethanesulfonic acid), MOPSO (2-hydroxy-3-morpholin-4-ylpropane-1-sulfonic acid), BES (2-[Bis(2- hydroxyethyl)amino]ethanesulfonic acid), MOPS (3-Morpholinopropane-1 -sulfonic acid), TES (2-[[1,3-dihydroxy-2-(hydroxymethyl)propan-2-yl]amino]ethanesulfonic acid), HEPES (2-[4-(2- hydroxyethyl)piperazin-1-yl]ethanesulfonic acid), DIPSO (3-[Bis(2-hydroxyethyl)amino]-2- hydroxy-1-propanesulfonic acid), MOBS (4-(4-Morpholinyl)-1-butanesulfonic acid), TAPSO (3- {[1 ,3-Dihydroxy-2-(hydroxymethyl)-2-propanyl]amino }-2-hydroxy-1-propanesulfonicacid), TRIS (3-{1, 1, 1,5,5,5-Hexamethyl-3-[(trimethylsilyl)oxy]-3-trisiloxanyl}propylmethacrylate), and Citrate (2-Oxido-1,2,3-propanetricarboxylate)

[0205] Antifoam agents refer to compounds which reduce and hinder the formation of foam on liquids. Non-limiting examples are insoluble oils, polydimethylsiloxanes and other silicones, certain alcohols, stearates and glycols.

[0206] Biocides are compounds which hinder or prevent the growth of microorganisms in the agrochemical compositions. Several suitable biocides are known in the art.

[0207] Agrochemical compositions for RNA comprising mixtures have been described in WO2022 / 235895, however, the agrochemical compositions described therein should not be understood to be limiting.

[0208] Preferred agrochemical compositions comprise at least one metal-ion sequestrant and a nonionic surfactant. A nonionic surfactant is a surfactant comprising a neutrally charged hydrophile and hydrophobe.

[0209] The agrochemical compositions may also comprise one or more secondary surfactants. Such secondary surfactants are selected from the group consisting of a cationic surfactant, a zwitterionic surfactant, an amphoteric surfactant, and combinations thereof.

[0210] A preferred metal-ion sequestrant is EDTA. Alkoxylated alcohols are preferably selected as nonionic surfactant.

[0211] The invention comprises also methods to prepare the mixtures or agrochemical compositions of the invention. The method comprises the steps of: a) providing at least one RNA comprising at least 18, 19, 20, 21 , 25, 50, 100, 150, 200, 250, 300, 350, 400, 450, or 500 contiguous nucleotides forming a nucleotide sequence having at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with a segment of a nucleotide sequence of the transcribed region of a CYP51 gene, or the reverse complement nucleotide sequence thereof, and b) providing at least one chemical or biological fungicide c) optionally, providing at least one auxiliary, and d) combining the RNA of a), the chemical or biological fungicide of b) and optionally the auxiliary of c). The steps of a), b) and c) can be performed in any sequence. For example, the step b) can be performed after or before or at the same time than step a).

[0212] The RNA, the chemical or biological fungicide are preferably selected as in the mixtures described above.

[0213] The RNA molecules of the invention can be prepared by methods known in the art such as by classical chemical synthesis, by in vitro transcription methods, viral induced expression, e.g. via recombinant plant infecting viruses, or by heterologous transcription in, e.g., microorganisms (bacteria, yeasts), cell cultures or plants. Accordingly, transcription can be mediated by an endogenous RNA polymerase of the host cell in vivo, or by a cloned RNA polymerase for transcription in vivo or in vitro. For example, they may be constructed as self-amplifying mRNA (SAM) comprising a first nucleotide sequence encoding a RNAdependent RNA polymerase (RdRp) operably linked to a second nucleotide sequence encoding a nucleotide sequence that forms a dsRNA in a plant cell, wherein the first nucleotide sequence is derived from a plant alphavirus.

[0214] The RNA molecules may be encapsidated in virus like particles, preferably virus like particles of plant infecting viruses or capsid proteins of bacteriophages, e.g. bacteriophages MS2 or Qbeta. Alternatively, the RNA molecules may be contained in empty cells of yeasts or bacteria.

[0215] The dsRNA molecules of the invention can be purified or isolated dsRNA. For example, RNA can be purified from a mixture by extraction with a solvent or resin, precipitation, electrophoresis, chromatography, or a combination thereof. Alternatively, the dsRNA may be used with no or only a minimum of purification to avoid losses due to sample processing. The RNA may be dried for storage or dissolved in an aqueous solution. The solution may contain buffers or salts to promote annealing, and / or stabilization of double-stranded RNA regions. The chemical or biological fungicides used in the mixtures and agrochemical compositions are well known in the art and are in most cases commercially available. Methods to produce the chemical or biological fungicides have also been described in the art.

[0216] Particular embodiments of the invention regarding methods to control phytopathogenic fungi:

[0217] A further embodiment of the invention is a method for controlling phytopathogenic fungi of the genus Erysiphe or Botrytis on a plant comprising: a. providing a plant infected or being at risk of being infected with a phytopathogenic fungus of the genus Erysiphe or Botrytis, b. contacting the plant and / or fungus of a. with at least one RNA comprising at least 18, 19, 20, 21 , 25, 50, 100, 150, 200, 250, 300, 350, 400, 450, or 500 contiguous nucleotides forming a nucleotide sequence having at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with a segment of a nucleotide sequence of the transcribed region of a CYP51 gene of a fungus of the genus Erysiphe or Botrytis, or the reverse complement nucleotide sequence thereof, c. contacting the plant and / or fungus of a. with at least one chemical or biological fungicide, wherein steps b. and c. can be performed at the same time or step b. before step c. or step c. before step b.

[0218] Preferably the at least one RNA is selected from an RNA described in at least one of the embodiments 1 to 20. Even more preferred, the at least one chemical or biological fungicide is selected from the preferred chemical or biological fungicides described for the mixtures of the invention.

[0219] Preferably the time between steps b and c is in growing order of preference less than 10, 7, 5, 3, 2 days, more preferred less than 1 day or steps b. and c are performed in growing order or preference in less than 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2 hours or less than 1 hour. In one embodiment steps b. and c. are performed at about the same time, because the at least one RNA of step b. and the at least one chemical or biological fungicide of step c. are mixed before the plant of step a is contacted with this mixture.

[0220] The selected chemical or biological fungicide has preferably a synergistic fungicidal effect when used in combination with the RNA of b. Preferably at least one RNA and / or at least one chemical or biological fungicide employed in the method are present in a fungicidally effective amount.

[0221] The RNA is preferably selected to target a CYP51 gene of a fungus of the species Erysiphe necator, in case the plant of a. is a host plant of Erysiphe necator, for example, but not excluding others, a species of the genus Vitis, preferably from the species Vitis vinifera.

[0222] The RNA is preferably selected to target a CYP51 gene of a fungus of the species Erysiphe cichoracearum, in case the plant of a. is a host plant of Erysiphe cichoracearum, for example, but not excluding others, a cucurbit species, preferred cucurbits are melon, cucumber, pumpkin, and squash.

[0223] The RNA is preferably selected to target a CYP51 gene of a fungus of the species Erysiphe neolycopersici, in case the plant of a. is a host plant of Erysiphe neolycopersici, for example, but not excluding others, a species of the genus Solanum, preferably from the species Solanum lycopersicum.

[0224] The RNA is preferably selected to target a CYP51 gene of a fungus of the species Botrytis cinerea, in case the plant of a. is a host plant of Botrytis cinerea. Botrytis cinerea has a very broad host range and infects more than 200 plant species. Preferred host plants to be protected against Botrytis cinerea are strawberries, grapes, including table grapes and wine grapes, tomatoes melon, cucumber, pumpkin, and squash, for example, but not excluding others, a species of the genus Solanum, preferably from the species Solanum lycopersicum.

[0225] In a preferred embodiment the methods for controlling phytopathogenic fungi employ more than one type of RNA, if the plant to be protected against fungal attack is a host plant to a fungus of the genus Erysiphe and a fungus of the genus Botrytis. In one embodiment, the method uses at least two types of RNA, wherein at least one type of RNA targets a CYP51 gene of a fungus of the species Botrytis cinerea and one type of RNA to target a CYP51 gene of a fungus of the species selected from Erysiphe necator, Erysiphe cichoracearum or Erysiphe neolycopersici.

[0226] A further embodiment of the invention is a method for controlling phytopathogenic fungi of the genus Erysiphe and Botrytis on a plant comprising: a. providing a plant infected or being at risk of being infected with a phytopathogenic fungus of the genus Erysiphe or Botrytis, b. contacting the plant and / or fungus of a. with at least one RNA selected to target a CYP51 gene of a fungus of the genus Erysiphe, c. contacting the plant and / or fungus of a. with at least one RNA selected to target a CYP51 gene of a fungus of the genus Botrytis, d. contacting the plant and / or fungus of a. with at least one chemical or biological fungicide, wherein steps b., c. and d. can be performed at the same time or step b. before step c or d. or step c before step b or d, or step d before step b or c, or any combination thereof.

[0227] Preferably the at least one RNA is selected from an RNA described in at least one of the embodiments 1 to 20. Even more preferred, the at least one chemical or biological fungicide is selected from the preferred chemical or biological fungicides described for the mixtures of the invention.

[0228] Preferably all steps of b., c. and d. are performed, in growing order of preference, in less than 10, 7, 5, 3, 2 days, more preferred less than 1 day or steps b., c. and d are performed, in growing order of preference, in less than 12, 11 , 10, 9, 8, 7, 6, 5, 4, 3, 2 hours or less than 1 hour. In one embodiment at least two of steps b. c. and d. are performed at about the same time, because the at least one of the RNAs of steps b. and c. is mixed with the at least one chemical or biological fungicide of step d, before the plant of step a is contacted with this mixture, or because at least one RNA of the of steps b. or c. is mixed with the at least one chemical or biological fungicide of step d, before the plant of step a is contacted with this mixture. In one embodiment the at least one RNA of steps b. and c. is mixed with the at least one chemical or biological fungicide of step d before the plant of step a is contacted with this mixture.

[0229] The plant is preferably selected from a plant species which is a host plant of at least one phytopathogenic fungus of the genus Erysiphe and at least one phytopathogenic fungus of the genus Botrytis and the at least one RNAs of steps b. and c. are selected to target the CYP51 genes of the respective fungi of the genus Erysiphe or Botrytis, respectively. Such combinations of host plant and fungi species of the genus Erysiphe and Botrytis are well known in the art. Non-limiting examples have been mentioned above. A further embodiment of the invention is a plant producing at least one RNA comprising at least 18, 19, 20, 21 , 25, 50, 100, 150, 200, 250, 300, 350, 400, 450, or 500 contiguous nucleotides forming a nucleotide sequence having, in growing order of preference, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with a segment of a nucleotide sequence of the transcribed region of a CYP51 gene of a fungus of the genus Erysiphe or Botrytis. Preferably the plant produces at least one type of RNA which targets a CYP51 gene of a fungus of the genus Botrytis and one type of RNA to target a CYP51 gene of a fungus of the genus Erysiphe.

[0230] Preferably the plant is a host plant to the species of the genus Botrytis and a host plant to the species of the genus Erysiphe, from which the target genes have been selected from.

[0231] Preferably the plant produces at least one type of RNA which targets a CYP51 gene of a fungus of the species Botrytis cinerea and one type of RNA to target a CYP51 gene of a fungus of the species selected from Erysiphe necator, Erysiphe cichoracearum or Erysiphe neolycopersici. Preferably the plant is a host plant to Botrytis cinerea and at least one fungus of the species selected from Erysiphe necator, Erysiphe cichoracearum or Erysiphe neolycopersici.

[0232] The plant may produce the at least one RNA because it has previously been contacted with such RNA, or it may produce the RNA because it comprises a transgenic sequence for the production of such RNA. In one embodiment the plant is non-transgenic but produces the at least one RNA because it has been contacted with such RNA e.g. comprised by an agrochemical composition. Methods to produce transgenic plants as well as methods to construct transgenic sequences to produce such RNAs are well known in the art and are for example described in WO2015 / 004174. In one embodiment the at least one chemical or biological fungicide is not procloraz.

[0233] Another embodiment of the invention is a method for controlling phytopathogenic fungi of the genus Erysiphe or Botrytis on a plant comprising: a. providing a plant producing at least one RNA comprising at least 18, 19, 20, 21, 25, 50, 100, 150, 200, 250, 300, 350, 400, 450, or 500 contiguous nucleotides forming a nucleotide sequence having, in growing order of preference, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with a segment of a nucleotide sequence of the transcribed region of a CYP51 gene of a fungus of the genus Erysiphe or Botrytis, and b. contacting the plant of a. with at least one chemical or biological fungicide at a point in time, when such plant is infected or is in danger of being infected with phytopathogenic fungi of the genus Erysiphe or Botrytis.

[0234] Preferably the plant is grown under conditions which puts it as risk of being infected by a phytopathogenic fungus of the genus Erysiphe or Botrytis or the plant is already infected with phytopathogenic fungus of the genus Erysiphe or Botrytis. A plant producing the RNA shows improved resistance to phytopathogenic fungi of the genus Erysiphe or Botrytis in comparison to a control plant of the same species, preferably the same plant variety, if the plant shows less symptoms of infection in comparison to the control plant, when grown and infected under the same conditions.

[0235] Preferably the at least one RNA is selected from an RNA described in at least one of the embodiments 1 to 20. Even more preferred, the at least one chemical or biological fungicide is selected from the preferred chemical or biological fungicides described for the mixtures of the invention. The selected chemical or biological fungicide has preferably a synergistic effect when used in combination with the at least one RNA of a. Preferably the selected chemical or biological fungicide(s) employed in the method are present in fungicidally effective amount(s).

[0236] The at least one RNA and the at least one chemical or biological fungicide used in the methods for controlling phytopathogenic fungi are preferably contacted with the plant by topical application to the plant parts which are already infected or being at risk of being infected with a phytopathogenic fungus of the genus Erysiphe or Botrytis, or to plant parts near by those actual or potential infection sites. In many cases the application is via a spraying more or less all plant parts which are accessible for spraying. The spraying liquid usually comprises a mixture of the invention or by diluting an agrochemical composition comprising such a mixture with a plant acceptable carrier. In other cases, the spraying liquid is prepared by adding the components of the mixture to the carrier used for dilution, e.g. by using a kit of at least parts described herein. In other cases, the at least one RNA and the at least one chemical or biological fungicide of the mixture are applied to the plant or plant parts in separate spraying liquids and applied at different points in time.

[0237] The methods for controlling phytopathogenic fungi of the genus Erysiphe or Botrytis can also be used to control phytopathogenic fungi of the genus Erysiphe and Botrytis, if at least one RNA is used which is capable to control at least one fungi species of the genus Erysiphe and at least one fungi species of the genus Botrytis. In many cases the methods for controlling phytopathogenic fungi use at least two RNAs, wherein one RNA is selected to control at least one fungi species of the genus Erysiphe and one RNA is selected to control at least one fungi species of the genus Botrytis. Methods to control phytopathogenic fungi of the genus Erysiphe and Botrytis are of particular interest if the plant to be protected is a host plant of at least at least one fungi species of the genus Erysiphe and at least one fungi species of the genus Botrytis and is grown under conditions, which put it at risk to be infected by such fungi or under which such plant is already infected by such fungi.

[0238] It has been observed that populations of phytopathogenic fungi apparently consisting of non- resistant strains can readily develop resistance against chemical or biological fungicides. The mixtures and agrochemical compositions can be applied under such conditions, too, to prevent the formation of resistance and the spread of resistant strains altogether. In this regard it is useful that they have strong activity also against non-resistant phytopathogenic fungi. Fungicide-resistant strains of various phytopathgenic fungi have been reported, with strains resistant to one or more fungicides from various mode of action classes being observed by target-site mutations in the genes of the respective proteins (e.g. Qol (C3, according to FRAC convention, for details www.frac.info), quinone outside stigmatellin binding subsite inhibitors (QoSI; C8), and quinone inside inhibitors (Qil ; C4): CytB target protein; sterol demethylaition (DMI, G1): Cyp51 / Erg11 ; carboxylic acid amides (CAA, H5): CesA3; SDHI (C2): SdhB, SdhC and SdhD; dicarboximides (E3): Os-1 (including Bos1, Daf1 etc.); keto reductase inhibitors (KRI; Class III SBIs; G3): Erg27. Such strains may have one or more resistances derived from one or more mutations of one or more genes encoding target proteins of various kinds of the fungicides and / or a resistance derived from an overexpression of the respective target protein. In addition, certain strains of fungi may have developed so-called multidrug resistance eventually leading to a broad cross resistance to many structurally and functionally unrelated compounds. "Multidrug resistance” (MDR) also called “pleiotropic drug resistance” (PDR) describes a resistance phenomen usually caused by overexpression of certain membrane transporters, leading to an increased activity of efflux pump which export certain substrates, e.g., fungal toxins but also fungicidal compounds. Examples of such membrane transporters include ATP-binding cassette (ABC) transporters and Major Facilitator Superfamily (MFS) transporters. Overexpression of membrane transporters can be confirmed, e.g., by measuring an amount of the transporter protein or of the corresponding mRNA. The measured amount of mRNA may be, e.g., 2-fold, 5-fold, 20-fold, up to 100-fold or more, relative to the mRNA amount of the corresponding fungicide-sensitive wild-type fungus.

[0239] The mixtures and agrochemical compositions are particularly useful to control phytopathogenic fungal strains showing one or more of these fungicide-resistances.

[0240] One embodiment of the invention uses the mixtures and agrochemical compositions described herein to control Erysiphe and / or Botrytis strains carrying a mutation resistant to one or more fungicides from various mode of action classes being observed by target-site mutations in the genes of the respective proteins (e.g. Qol (C3, according to FRAC convention, for details www.frac.info), quinone outside stigmatellin binding subsite inhibitors (QoSI; C8), and quinone inside inhibitors (Qil; C4): CytB target protein; sterol demethylaition (DMI, G1): Cyp51 / Erg11; carboxylic acid amides (CAA, H5): CesA3; SDHI (C2): SdhB, SdhC and SdhD; dicarboximides (E3): Os-1 (including Bos1 , Daf1 etc.); keto reductase inhibitors (KRI; Class III SBIs; G3): Erg27 and / or overexpression of the respective target protein and / or showing Multidrug resistance. One of these mutations providing resistance against DMI type of fungicides is a mutation leading to the amino acid exchange of Y134F in the Cyp51 gene.

[0241] One embodiment of the invention uses the mixtures and agrochemical compositions described herein to control Erysiphe and / or Botrytis strains carrying this Y134F mutation. Preferably the strains carrying the Y134F mutation are selected from strains of Erysiphe necator, Erysiphe cichoracearum, Erysiphe neolycopersici or Botrytis cinerea.

[0242] When employed in plant protection, the amounts of active substances, meaning the at least one RNA and at least one chemical or biological fungicide, applied are, depending on the kind of effect desired, from 0.001 to 2 kg per ha, preferably from 0.005 to 2 kg per ha, more preferably from 0.05 to 0.9 kg per ha, and in particular from 0.1 to 0.75 kg per ha.

[0243] Preferred amounts of the at least one RNA per ha are between 1 to 200 g per ha, or 1 to 100 g per ha, or 1 to 50 g per ha, or 10 to 200 g per ha, or 20 to 180 g per ha, or 50 to 200 g per ha. Preferred concentrations in parts per million (ppm) of the at least one RNA is between 1 to 200, or 1 to 100, or 1 to 50, or 10 to 200, or 20 to 180, or 50 to 200.

[0244] The user applies the agrochemical composition usually from a predosage device, a knap-sack sprayer, a spray tank, a spray plane, or an irrigation system. Usually, the agrochemical composition is made up with water, buffer, and / or further auxiliaries to the desired application concentration and the ready-to-use spray liquor or the agrochemical composition according to the invention is thus obtained. Usually, 20 to 2000 liters, preferably 50 to 400 liters, of the ready- to-use spray liquor are applied per hectare of agricultural useful area.

[0245] The agrochemical compositions generally comprise between 0.01 and 95 %, preferably between 0.1 and 90 %, more preferably between 1 and 70 %, and in particular between 10 and 60 %, by weight of active substances. The active substances are employed in a purity of from 90 % to 100 %, preferably from 95 % to 100 % (according to NMR spectrum).

[0246] According to the invention, the solid material (dry matter) of the biological fungicides (with the exception of oils such as terpene oils) are considered as active components (e.g. to be obtained after drying or evaporation of the extraction or suspension medium in case of liquid formulations of the microbial pesticides). The weight ratios and percentages used for a biological extract such as Reynoutria sachalinensis extract are based on the total weight of the dry content (solid material) of the respective extract(s).

[0247] The total weight ratios of compositions comprising at least one microbial pesticide in the form of viable microbial cells including dormant forms, can be determined using the amount of colony forming units “CFU” of the respective microorganism to calculate the total weight of the respective active component with the following equation that 1 x 1010CFU equals one gram of total weight of the respective active component. Colony forming unit is measure of viable microbial cells. When mixtures comprising microbial pesticides are employed in crop protection, the application rates range from 1 x 106to 5 x 1016(or more) CFU / ha, preferably from 1 x 108to 1 x 1013CFU / ha, and even more preferably from 1 x 109to 5 x 1015CFU / ha and in particular from 1 x 1012to 5 x 1014CFU / ha.

[0248] In the mixtures the weight / weight ratio of the at least one RNA and the at least one chemical or biological fungicide generally depends from the properties of the components used, usually it is in the range of from 1 : 10,000 to 10,000: 1 , or from 1 : 1000 to 1000: 1 , often from 1 : 100 to 100: 1 , regularly from 1 :50 to 50: 1 , preferably from 1 :20 to 20: 1 , more preferably from 1 : 10 to 10: 1 , even more preferably from 1 :4 to 4:1 and in particular from 1:2 to 2:1. Furter possible weight ratios are in the range of 130:1 to 1 :130, often from 64:1 to 1:64, preferably from 32:1 to 1 :32, more preferred from 16:1 to 1:16 or 8:1 to 1:8.

[0249] According to further embodiments, the weight / weight ratio of the at least one RNA and the at least one chemical or biological fungicide is usually in the range of from 1000:1 to 1:1, often from 100: 1 to 1 :1 , regularly from 50:1 to 1 :1 , preferably from 20:1 to 1:1 , more preferably from 10:1 to 1 :1, even more preferably from 4:1 to 1:1 and in particular from 2:1 to 1 :1. Furter possible weight ratios are in the range of 130:1 to 1 :1 , often from 64:1 to 1 :1 , preferably from 32:1 to 1 :1, more preferred from 16:1 to 1:1 or 8:1 to 1:1.

[0250] According to further embodiments, the weight / weight ratio of the at least one RNA and the at least one chemical or biological fungicide usually is in the range of from 1 : 1 to 1 : 1000, often from 1:1 to 1 :100, regularly from 1 :1 to 1:50, preferably from 1 :1 to 1:20, more preferably from 1:1 to 1:10, even more preferably from 1:1 to 1:4 and in particular from 1:1 to 1 :2.

[0251] Furter possible weight ratios are in the range of 1:1 to 1 :130, often from 1 :1 to 1:64, preferably from 1 : 1 to 1 : 32, more preferred from 1 : 1 to 1 : 16 or 1 : 1 to 1 :8.

[0252] According to further embodiments, the weight / weight ratio of the at least one RNA and the at least one chemical or biological fungicide usually is in the range of from 1000: 1 to 1 : 10, often from 100: 1 to 1 :10, regularly from 50:1 to 1:10, preferably from 20:1 to 1 :10, more preferably from 10:1 to 1:10, even more preferably from 4:1 to 1 :10 and in particular from 2:1 to 1:10. Furter possible weight ratios are in the range of 130:1 to 1 :10, often from 64:1 to 1:10, preferably from 32:1 to 1 :1 ,0 more preferred from 16:1 to 1 :10 or 8:1 to 1:10, or 4:1 to 1:10, or 2:1 to 1:10.

[0253] According to further embodiments, the weight / weight ratio of the at least one RNA and the at least one chemical or biological fungicide usually is in the range of from 10:1 to 1 :1000, often from 10:1 to 1:100, regularly from 10:1 to 1 :50, preferably from 10:1 to 1 :20, more preferably from 10:1 to 1:10, even more preferably from 10:1 to 1:4 and in particular from 10:1 to 1 :2. Furter possible weight ratios are in the range of 10:1 to 1:130, often from 10:1 to 1 :64, preferably from 10:1 to 1 : 32, more preferred from 10:1 to 1:16 or 10:1 to 1:8, or 10:1 to 1 :4, or 10:1 to 1 :2.

[0254] The amino acid and nucleotide sequences described herein have been derived from public available genomic sequence information of fungal strains collected in the United States of America and in Germany. The sources of these strains are disclosed in:

[0255] Jones et al. "Adaptive genomic structural variation in the grape powdery mildew pathogen, Erysiphe necator1' BMC Genomics 2014, 15:1081

[0256] Amselem J et al., "Genomic analysis of the necrotrophic fungal pathogens Sclerotinia sclerotiorum and Botrytis cinerea ", PLoS Genet, 2011 Aug 18;7(8):e1002230, Table S26 Fungal strains used for the construction of the phylogeny shown in Figure 2.

[0257] Wu et al. "Comparative genome analyses reveal sequence features reflecting distinct modes of host-adaptation between dicot and monocot powdery mildew" BMC Genomics (2018) 19:705 https: / / doi.Org / 10.1186 / S12864-018-5069-z

Claims

Claims1) A mixture comprising: a) at least one RNA comprising at least 18, 19, 20, 21, 25, 50, 100, 150, 200, 250, 300, 350, 400, 450, or 500 contiguous nucleotides forming a nucleotide sequence having at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with a segment of a nucleotide sequence of the transcribed region of a CYP51 gene, or the reverse complement nucleotide sequence thereof, and b) at least one chemical or biological fungicide.2) The mixture of claim 1 , wherein the CYP51 gene encodes a protein sequence having at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with a protein sequence selected from the group consisting of SEQ ID Nos: 1, 88, 119 and 57.3) The mixture of claim 1 or 2, wherein the CYP51 gene comprises a nucleotide sequence selected from the group consisting of SEQ ID Nos: 2, 3, 4, 89, 90, 91, 120, 121 , 122, 58, 59 and 60.4) The mixture of any one of claims 1 to 3, wherein the at least one RNA is selected from: a. an RNA comprising at least 18, 19, 20, 21 , 25, 50, 100, 150, 200, 250, 300, 350, 400, 450, or 500 contiguous nucleotides forming a nucleotide sequence having at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with a segment of a nucleotide sequence of the transcribed region of a CYP51 gene, or b. an RNA comprising at least 18, 19, 20, 21 , 25, 50, 100, 150, 200, 250, 300, 350, 400, 450, or 500 contiguous nucleotides forming a nucleotide sequence, which is the reverse complement to a nucleotide sequence having at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with a segment of a nucleotide sequence of the transcribed region of a CYP51 gene, or c. a dsRNA comprising a sense nucleotide sequence of an RNA of a. and an anti-sense nucleotide sequence of an RNA of b., wherein the arrangement of the RNA of a. and the RNA of b. within the dsRNA molecule allows hybridization of the RNA of a. and the RNA of b. at room temperature.5) The mixture of any one of claims 1 to 4, wherein the at least one RNA is selected from: a. an RNA comprising a nucleotide sequence having at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with a nucleotidesequence selected from the group consisting of SEQ ID Nos: 5, 8, 11, 14, 17, 20, 23,26, 29, 92, 95, 98, 101 , 104, 107, 110, 113, 116, 123, 126, 129, 132, 135, 138, 141,144, 147, 33, 37, 41 , 45, 48, 51, 54, 61 , 64, 67, 70, 73, 76, 79, 82 and 85, or b. an RNA comprising a nucleotide sequence having at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with a nucleotide sequence selected from the group consisting of SEQ ID Nos: 6, 9, 12, 15, 18, 21 , 24,27, 30, 93, 96, 99, 102, 105, 108, 111, 114, 117, 124, 127, 130, 133, 136, 139, 142,145, 148, 34, 38, 42, 46, 49, 52, 55, 62, 65, 68, 71, 74, 77, 80, 83, 86, 274, 276, 278, 280, 282, 284, 286 and 288, or c. an RNA comprising a nucleotide sequence having at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with a nucleotide sequence selected from the group consisting of SEQ ID Nos: 7, 10, 13, 16, 19, 22, 25, 28, 31, 94, 97, 100, 103, 106, 109, 112, 115, 118, 125, 128, 131, 134, 137, 140, 143, 146, 149, 35, 39, 43, 47, 50, 53, 56, 63, 66, 69, 72, 75, 78, 81, 84 , 87, 275, 277, 279, 281 , 283, 285, 287 and 289.6) The mixture of any one of claims 1 to 5, comprising: a. at least one RNA, or RNA segment, comprising at least 18, 19, 20, 21, 25, 50, 100, 150, 200, 250, 300, 350, 400, 450, or 500 contiguous nucleotides forming a nucleotide sequence having at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with a segment of a nucleotide sequence of the transcribed region of a CYP51 gene encoding a protein sequence selected from the group consisting of SEQ I D Nos: 1 , 88 and 119, and b. at least one RNA or RNA segment, comprising at least 18, 19, 20, 21, 25, 50, 100, 150, 200, 250, 300, 350, 400, 450, or 500 contiguous nucleotides forming a nucleotide sequence having at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with a segment of a nucleotide sequence of the transcribed region of a CYP51 gene encoding a protein sequence of SEQ ID Nos: 57.7) The mixture of any one of claims 1 to 6, wherein the at least one RNA is selected from: a. an RNA comprising at least 18, 19, 20, 21 , 25, 50, 100, 150, 200, 250, 300, 350, 400, 450, or 500 contiguous nucleotides forming a nucleotide sequence having at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with a nucleotide sequence from nucleotide 300 to nucleotide 1000 of a nucleotide sequence selected the group consisting of SEQ ID Nos: 4, 91 , 122, and 60, or b. an RNA comprising a nucleotide sequence having at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with a nucleotidesequence selected from the group consisting of SEQ ID Nos: 34, 274, 276, 278, 280, 282, 284, 286, 288, 35, 275, 277, 279, 281, 283, 285, 287 and 289, or c. a dsRNA comprising a sense nucleotide sequence having at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with a nucleotide sequence selected from the group consisting of SEQ ID No. 34, 274, 276, 278, 280, 282, 284, 286 and 288, and comprising an antisense nucleotide sequence having at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with a nucleotide sequence selected from the group consisting of SEQ ID No. 35, 275, 277, 279, 281 , 283, 285, 287 and 289, wherein the arrangement of the sense nucleotide sequence and the antisense nucleotide sequence within the dsRNA molecule allows hybridization of the sense nucleotide sequence and the antisense nucleotide sequence at room temperature.8) The mixture of any one of claims 1 to 7, wherein the RNA is present in a fungicidally effective amount.9) The mixture of any one of claims 1 to 8, wherein the chemical or biological fungicide is selected from the following groups: a. respiration inhibitors b. sterol biosynthesis inhibitors c. inhibitors of cell division and cytoskeleton d. signal transduction inhibitors e. inhibitors with multi-site action f. plant defence inducers, and g. biopesticides.10) The mixture of any one of claims 1 to 9, wherein the chemical or biological fungicide is selected from the following groups: a. azoxystrobin, kresoxim-methyl, pyraclostrobin, trifloxystrobin, boscalid, pyd- iflumetofen and meptyldinocap, b. difenoconazole, fenbuconazole, flutriafol, myclobutanil, penconazole, tebuconazole, tetraconazole, mefentrifluconazole, spiroxamine and fenhexamide, c. metrafenone, d. proquinazid, e. copper, copper acetate, copper hydroxide, copper oxychloride, basic copper sulfate and sulfur, and f. fosetyl, fosetyl-aluminum and potassium phosphonate, andg. Bacillus subtilis, Bacillus subtilis var. amyloliquefaciens, Bacillus velezensis, Reynoutria sachalinensis extract.11) The mixture of any one of claims 1 to 10, wherein the chemical or biological fungicide is present in a fungicidally effective amount.12) The mixture of any one of claims 1 to 11 , wherein the weight / weight ratio of the at least one RNA and the at least one chemical or biological fungicide is in the range of from 1:1000 to 1000:1.13) The mixture of any one of claims 1 to 12, wherein the mixture comprises a transfer agent.14) A kit of at least three parts to prepare a mixture as claimed in any one of claims 1 to 12, comprising: a) a part comprising at least one RNA as described in any one of claims 1 to 7 in a concentrated form, and b) a part comprising at least one chemical or biological fungicide as described in claims 9 or10 in a concentrated form, and c) a part comprising instructions how to combine part a) and part b) to prepare a mixture as claimed in any one of claims 1 to 12.15) A kit of at least three parts to prepare a mixture as claimed in claim 13, comprising: a. a part comprising at least one RNA as described in any one of claims 1 to 7 in a concentrated form and comprising at least one chemical or biological fungicide as described in claims 9 or 10 in a concentrated form and b. a part comprising at least one transfer agent in a concentrated form, and c. a part comprising instructions how to combine part a) and part b) to prepare a mixture as claimed in claim 13.16) An agrochemical composition comprising: a. at least one RNA as claimed in any one of claims 1 to 7, b. at least one chemical or biological fungicide as described in claims 9 or 10, and c. an auxiliary.17) A method to prepare a mixture as claimed in any one of claims 1 to 13 or an agrochemical composition as claimed in claim 16, comprising: a. providing at least one RNA as claimed in any one of claims 1 to 7, b. providing at least one chemical or biological fungicide as claimed in claims 9 or 10, andc. combining the at least one RNA of a. and the at least one fungicide of b.18) A method for controlling phytopathogenic fungi of the genus Erysiphe or Botrytis on a plant comprising: a. providing a plant infected or being at risk of being infected with a phytopathogenic fungus of the genus Erysiphe or Botrytis, b. contacting the plant and / or fungus of a. with at least one RNA as claimed in any one of claims 1 to 7, c. contacting the plant and / or fungus of a. with at least one chemical or biological fungicide as claimed in in claims 9 or 10, wherein steps b. and c. can be performed at the same time or step b. before step c. or step c. before step b.19) A method for controlling phytopathogenic fungi of the genus Erysiphe and Botrytis on a plant comprising: a. providing a plant infected or being at risk of being infected with a phytopathogenic fungus of the genus Erysiphe and Botrytis, b. contacting the plant and / or fungus of a. with at least one RNA as claimed in any one of claims 1 to 7 selected to target a CYP51 gene of a fungus of the genus Erysiphe, c. contacting the plant and / or fungus of a. with at least one RNA as claimed in any one of claims 1 to 7 selected to target a CYP51 gene of a fungus of the genus Botrytis, d. contacting the plant and / or fungus of a. with at least one chemical or biological fungicide as claimed in in claims 9 or 10, wherein steps b., c. and d. can be performed at the same time or step b. before step c or d. or step c before step b or d, or step d before step b or c, or any combination thereof.20) A method for controlling phytopathogenic fungi of the genus Erysiphe or Botrytis on a plant comprising: a. providing a plant producing at least one RNA as described in any of claims 1 to 7, b. contacting the plant of a. with at least one chemical or biological fungicide as described in claims 9 or 10 at a point in time, when such plant is infected or is in dan-ger of being infected with phytopathogenic fungi of the genus Erysiphe or Botrytis.21) The use of at least one RNA as described in any of claims 1 to 7 in a mixture as claimed in any one of claims 1 to 13, or to prepare a kit of at least three parts as claimed in claims 14 or 15 or in an agrochemical composition as claimed in claim 16, or in a method as claimed in any one of claims 17 to 20.

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