Anti-insect CDA nanobodies and uses thereof

Abstract

Anti-insect CDA nanobodies are provided. Accordingly, there is provided a nanobody which specifically binds to a non-linear epitope of insect CDA, said non-linear epitope is in the catalytic and / or chitin binding domain of the insect CDA, wherein binding of said nanobody to said insect CDA confers an insect control activity to said nanobody. Also provided are anti-insect CDA nanobodies defined by specific CDR sequences. Also provided are polynucleotides encoding the nanobodies, host cells expressing the nanobodies and methods of using them.

Description

ANTI-INSECT CDA NANOBODIES AND USES THEREOFRELATED APPLICATION / SThis application claims the benefit of priority of US Provisional Patent Application No. 63 / 623,274 filed on January 21, 2024, the contents of which are incorporated herein by reference in their entirety.SEQUENCE LISTING STATEMENTThe XML file, entitled 101891.xml, created on January 14, 2025, comprising 431,963 bytes, submitted concurrently with the filing of this application is incorporated herein by reference.FIELD AND BACKGROUND OF THE INVENTIONThe present invention, in some embodiments thereof, relates to anti-insect CDA nanobodies and uses thereof.Management of insect pests in the past 70 years has been achieved mainly through application of synthetic pesticides. Since the discovery of the insecticidal properties of DDT by Paul Muller in 1939, hundreds of insecticidal compounds have been developed, accompanied by a relatively steady increase in insecticide use. Most of the currently used chemical insecticides have a high potential for damaging the ecosystem, they are toxic to humans directly or through the food chain and their use is also impeded by development of genetic insect resistance. The most prominent biological solutions currently in use include beneficial organisms or natural enemies that reduce harm caused by insects, pheromones that act as bait or harm reproduction, release of sterile males, spraying with bacillus thuringiensis toxin or genetically modified crops containing a gene for Bacillus thuringiensis toxin that is lethal to the insects but not to humans. However, these biological solutions also have disadvantage, including low efficiency, danger of violating the natural ecological balance and development genetic insect resistance (e.g., in the case of the use of Bacillus toxin).Nanobodies, also known as VHH antibodies, are single domain antibodies which practically contain the heavy chain of an antibody (HCAb) and completely lack the light chain. They were discovered in the blood of camels by Raymond Hamers who was credited with this discovery in 1989 at Vrije Universiteit Brussel. Nanobodies are the smallest available intact antigen binding fragment (Cortez-Retamozo et al., 2004; Revets et al., 2005) with a size of approximately 15 kDa. The nanobodies have significant advantages including high production yield in a broad variety of expression systems, their minimal size allows high accessibility to theirepitopes, high physical-chemical stability, reversible refolding and high solubility in aqueous solutions, highly homogenous showing no signs of spontaneous dimerization and ability to specifically recognize unique epitopes with sub-nanomolar affinities. The use of nanobodies as insecticides has been previously suggested (see e.g. EP Patent Application Publication Nos: EP3415010 and EP2609116; US Patent Publication No: US9516879; US Patent Application Publication No: US9803003B2; and International Patent Application Publication No. W 02014191146).Chitin deacetylase (CDA) is an enzyme that convert chitin into chitosan, thereby influencing the mechanical and permeability properties of structures such as the cuticle and peritrophic matrices. Most of the CDA-like proteins have a putative signal peptide consistent with their role in modifying extracellular chitin in both cuticle and peritrophic membrane during morphogenesis and molting [Dixit R. et al. (2008) Insect Biochem Mol Biol. 38(4): 440-51]. Defects in the CDA can disrupt the feeding and digestion processes of insects, inhibit their growth, impair their development and even induce death [Yingchen et al (2021) J Pestic Sci. 46(1): 43- 52]. Indeed, inhibition of insect CDA by small molecules or RNA interference was shown to induce developmental defects and abnormal growth and molting, and to increase mortality [Yingchen et al (2021) J Pestic Sci. 46(1): 43-52; Jian-Jian Wu et al. (2018) Insect Molecular Biology 28(1): 52-64; Chikate et al. (2016) Pestic Biochem Physiol. 133: 44-51; Zhao et al. (2021) Pesticide Biochemistry and Physiology 173: :104770]. Anti-insect CDA nanobodies and their use as insecticides have also been disclosed (International Patent Application Publication No. W 02021 / 095031).SUMMARY OF THE INVENTIONAccording to an aspect of some embodiments of the present invention there is provided a nanobody which specifically binds to a non-linear epitope of insect CDA, the non-linear epitope is in the catalytic and / or chitin binding domain of the insect CDA, wherein binding of the nanobody to the insect CDA confers an insect control activity to the nanobody.According to an aspect of some embodiments of the present invention there is provided a nanobody which specifically binds to a non-linear epitope of insect CDA, the non-linear epitope comprises an amino acid residue selected from the group consisting of D170, D175, E360, D361, D365, D384, Y387, N388, N391, H392, D395, Y398, E399, E419, E422, E430, S433 and S434 of SEQ ID NO: 1 or the corresponding amino acid residue in orthologous polypeptides, wherein binding of the nanobody to the insect CDA confers an insect control activity to the nanobody.According to some embodiments of the invention, the non-liner epitope of the insect CDA comprises all of the amino acid residues.According to some embodiments of the invention, the amino acid residue is selected from the group consisting of E360, D361, D365, D384, Y387, N388, N391, H392, D395, Y398, E399, E419, E422, E430, S433 and S434 of the SEQ ID NO: 1 or the corresponding amino acid residue in the orthologous polypeptides.According to some embodiments of the invention, the non-liner epitope of the insect CDA comprises the amino acid residues E360, D361, D365, D384, Y387, N388, N391, H392, D395, Y398, E399, E419, E422, E430, S433 and S434 of the SEQ ID NO: 1 or the corresponding amino acid residue in the orthologous polypeptides.According to some embodiments of the invention, the non-liner epitope of the insect CDA comprises the amino acid residues E360, D361, D365, D384, H392, E419 and E422 of the SEQ ID NO: 1 or the corresponding amino acid residue in the orthologous polypeptides.According to an aspect of some embodiments of the present invention there is provided a nanobody which specifically binds to a non-linear epitope of insect CDA, the non-linear epitope comprises an amino acid residue selected from the group consisting of V22, E23, L24, C25, D46, 148, 168, E99, P100, L101, C102, R286, A287, G293, G294, N295, N296, Q297, M301, E302, E303, Q304, L307, Y3O8, D309, S310, T311, 1312, P319, P320, P323, Y 324, T325, Y327, F328, H332, R333, C334, H335, G336, N337, L338, Q339, S340, C341, P342, T343, R344, W349, E350, M351, V352, N354, E355, D357, R358, E360, P362, N364, E366, M373, V374, D375, N391, H392, D395, Y398, E399, A403, P404, L405, G406, R415, S434, M443, T444, Q445, V446, 1447, Q448, P475, C477, W478, V479, P480, S482, C483, K484, L485, T499, C500, V501, R502, P508, L510, N511, D512, D516, G517, H518 and Y519 of SEQ ID NO: 1 or the corresponding amino acid residue in orthologous polypeptides, wherein binding of the nanobody to the insect CDA confers an insect control activity to the nanobody.According to some embodiments of the invention, the non-liner epitope of the insect CDA comprises all of the amino acid residues.According to some embodiments of the invention, the amino acid residue is selected from the group consisting of W349, E350, M351, V352, N354, E355, D357, R358, E360, P362, N364, E366, M373, V374, D375, N391, H392, D395, Y398, E399, A403, P404, L405, G406, R415, S434, M443, T444, Q445, V446, 1447 and Q448, of the SEQ ID NO: 1 or the corresponding amino acid residue in the orthologous polypeptides.According to some embodiments of the invention, the non-liner epitope of the insect CDA comprises the amino acid residues W349, E350, M351, V352, N354, E355, D357, R358, E360,P362, N364, E366, M373, V374, D375, N391, H392, D395, Y398, E399, A403, P404, L405, G406, R415, S434, M443, T444, Q445, V446, 1447 and Q448 of the SEQ ID NO: 1 or the corresponding amino acid residue in the orthologous polypeptides.According to some embodiments of the invention, the amino acid residue is selected from the group consisting of C25, D46, 148, 168 of the SEQ ID NO: 1 or the corresponding amino acid residue in the orthologous polypeptides.According to some embodiments of the invention, the non-liner epitope of the insect CDA comprises the amino acid residues C25, D46, 148, 168 of the SEQ ID NO: 1 or the corresponding amino acid residue in the orthologous polypeptides.According to some embodiments of the invention, the non-liner epitope of the insect CDA comprises the amino acid residues E350, M351 and V352 of the SEQ ID NO: 1 or the corresponding amino acid residue in the orthologous polypeptidesAccording to an aspect of some embodiments of the present invention there is provided a nanobody which specifically binds to an insect CDA, the nanobody comprises three complementarity determining regions (CDRs) as set forth in SEQ ID NOs: 3-5, 7-9, 11-13, 15-17, 19-21, 23-25, 27-29, 31-33, 35-37, 39-41, 43-45, 47-49, 51-53, 55-57, 59-61, 63-65, 67-69, 71- 73, 75-77, 79-81, 83-85, 87-89, 91-93, 95-97, 99-101, 103-105, 107-109, 111-113, 115-117, 119- 121, 123-125, 127-129, 131-133, 135-137, 139-141, 143-145, 147-149, 151-153, 155-157, or 159- 161 arranged in a sequential order from N to C on the nanobody, wherein binding of the nanobody to the insect CDA confers an insect control activity to the nanobody.According to some embodiments of the invention, the nanobody comprises three CDRs as set forth in the SEQ ID NOs: 15-17, 83-85 or 95-97 arranged in a sequential order from N to C on the nanobody.According to some embodiments of the invention, the nanobody comprises three CDRs as set forth in SEQ ID NOs: 15-17 arranged in a sequential order from N to C on the nanobody.According to some embodiments of the invention, the nanobody comprises three CDRs as set forth in SEQ ID NOs: 83-85 arranged in a sequential order from N to C on the nanobody.According to some embodiments of the invention, the nanobody further comprising a heterologous toxin moiety having an insect control activity.According to some embodiments of the invention, the nanobody downregulates activity of the insect CDA.According to an aspect of some embodiments of the present invention there is provided a polynucleotide encoding the nanobody.According to an aspect of some embodiments of the present invention there is provided a nucleic acid construct comprising the polynucleotide and a cis-acting regulatory element for directing expression of the polynucleotide.According to an aspect of some embodiments of the present invention there is provided a host cell comprising the nanobody or a polynucleotide or a nucleic acid construct encoding it.According to an aspect of some embodiments of the present invention there is provided a method of producing an insect control nanobody, the method comprising culturing the cell.According to some embodiments of the invention, the method comprising isolating the nanobody.According to an aspect of some embodiments of the present invention there is provided a method of insect control, the method comprising contacting the insect with the nanobody, a polynucleotide or a nucleic acid construct encoding same or a host cell expressing same.According to some embodiments of the invention, the contacting comprises applying the nanobody directly to the insect.According to some embodiments of the invention, the contacting comprises applying the nanobody to an organism or a surface, which may be in contact with the insect.According to some embodiments of the invention, the nanobody is formulated for delivery by spraying, irrigation and / or fumigation.According to some embodiments of the invention, the nanobody is formulated as a liquid formulation.According to some embodiments of the invention, the nanobody is formulated as a dry formulation.According to an aspect of some embodiments of the present invention there is provided a plant comprising the nanobody or a polynucleotide or a nucleic acid construct encoding same.According to some embodiments of the invention, the plant being a transgenic plant.According to an aspect of some embodiments of the present invention there is provided a commodity product comprising the nanobody.According to some embodiments of the invention, the commodity product is produced from the plant of any one of claims 31-32.According to some embodiments of the invention, the insect is selected from the group consisting of moth, whitefly, aphid, stinkbug, hopper, beetle and honeybee.According to some embodiments of the invention, the insect is a moth.According to some embodiments of the invention, the moth is Spodopterafrugiperda.According to some embodiments of the invention, the insect is a whitefly.According to some embodiments of the invention, the whitefly is Bemisia tabaci.According to some embodiments of the invention, the insect is an aphid.According to some embodiments of the invention, the aphid is Myzus persicae.Unless otherwise defined, all technical and / or scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the invention pertains. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of embodiments of the invention, exemplary methods and / or materials are described below. In case of conflict, the patent specification, including definitions, will control. In addition, the materials, methods, and examples are illustrative only and are not intended to be necessarily limiting.BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGSSome embodiments of the invention are herein described, by way of example only, with reference to the accompanying drawings. With specific reference now to the drawings in detail, it is stressed that the particulars shown are by way of example and for purposes of illustrative discussion of embodiments of the invention. In this regard, the description taken with the drawings makes apparent to those skilled in the art how embodiments of the invention may be practiced.In the drawings:FIG. 1 is a graph demonstrating the effect of the anti-CDA nanobodies CDA-SF-1D (SEQ ID NO: 14), CDA-SF-2C (SEQ ID NO: 82), and CDA-SF-3B (SEQ ID NO: 94) on Spodoptera frugiperda mortality in the cotton leaf disc bioassay, using 0.1 ml nanobody at a concentration of 2 - 4 mg / ml as compared to PBS control. 1 larva stage 1-2 was added to each well, with 12 repetitions for each treatment in three independent studies; and mortality was evaluated following 4 days of treatment. Data is presented as average ± SE.FIG. 2 is a dose-respone graph demonstrating the effect of the anti-CDA nanobody CDA- SF-1D (SEQ ID NO: 14) on Myzus persicae mortality in the liquid bioassay, following feeding with the nanobody in concentrations between 0.01 to 2 mg / ml. Each sample included 10 none winged nymph stage aphids with 3 repetitions for each treatment; and mortality was evaluated following 48 hours of incubation.FIG. 3 is a dose-respone graph demonstrating the effect of the anti-CDA nanobody CDA- SF-1D (SEQ ID NO: 14) on Bemisia tabaci mortality in the liquid bioassay, following feeding with the nanobody in concentrations between 0.05 to 2.5 mg / ml. Each sample included 50 adults aphids with 3 repetitions for each treatment; and mortality was evaluated following 48 hours of incubation.FIG. 4 is a dose-respone graph demonstrating the effect of the anti-CDA nanobody CDA- SF-2C (SEQ ID NO: 82) on Myzus persicae mortality in the liquid bioassay, following feeding with the nanobody in concentrations between 0.05 to 2.5 mg / ml. Each sample included 10 none winged nymph stage aphids with 3 repetitions for each treatment; and mortality was evaluated following 48 hours of incubation.FIG. 5 is a graph demonstrating the effect of the anti-CDA nanobody CDA-SF-1D (SEQ ID NO: 14) on Myzus persicae mortality, in the pepper plant bioassay (in which the nanobodies were applied prior to insect introduction), using 0.6 ml nanobody at a concentration of 0.6 mg / ml as compared to PBS control. Each plant was inoculated with 20 aphids at stages N2-N3, with 4 repetitions for each treatment; and mortality was evaluated following 4 days of treatment. Data is presented as average ± SE.FIG. 6 is a graph demonstrating the effect of the anti-CDA nanobody CDA-SF-2C (SEQ ID NO: 82) on Myzus persicae mortality, in the pepper plant bioassay (in which the nanobodies were applied prior to insect introduction), using 1.4 ml nanobody at a concentration of 2 mg / ml as compared to PBS control. Each plant was inoculated with 20 aphids at stages N2-N3, with 4 repetitions for each treatment; and mortality was evaluated following 4 days following treatment with the nanobody. Data is presented as average ± SE.FIG. 7 is a graph demonstrating the effect of the anti-CDA nanobody CDA-SF-2C (SEQ ID NO: 82) on Myzus persicae mortality, in the pepper green-house plant bioassay (in which the nanobodies were applied post insect introduction), using 0.8 ml nanobody at a concentration of 1 mg / ml or 3 mg / ml. Each plant was inoculated with 20 nymph stage aphids prior to nanobody treatment, with 3-10 independent repetitions for each treatmemt in 3 independent studies; and mortality was evaluated on days 1 and 5 after treatment with the nanobody. Data is presented as average ± SE, *** - p <0 001.FIG. 8 is a graph demonstrating the effect of the anti-CDA nanobody CDA-SF-2C (SEQ ID NO: 82) on Bemisia tabaci mortality, in the pepper green-house plant bioassay (in which the nanobodies were applied post insect introduction), using 0.8 ml nanobody at a final concentration of 1 mg / ml or 3 mg / ml sprayed twice on days 0 and 6. Each plant was inoculated with 100 adult aphids prior to first nanobody treatment, with 4-6 independent repetitions for each treatmemt in 2 independent studies; and mortality was evaluated on days 1, 5, 7 and 12 after first treatment with the nanobody. Data is presented as average ± SE.FIG. 9 is a graph demonstrating the effect of the anti-CDA nanobody CDA-SF-2C (SEQ ID NO: 82) on Spodopterafrugiperda mortality, in the cotton green-house plant bioassay (in which the nanobodies were applied post insect introduction), using 1.5 ml nanobody at a finalconcentration of 1 mg / ml or 3 mg / ml. Each plant was inoculated with 16 L2-stage larvae prior to nanobody treatment, with 3-10 independent repetitions for each treatment in 4 independent studies; and mortality was evaluated on days 1 and 5 after treatment with the nanobody. Data is presented as average ± SE, * - p <0.05), ** - p < 0.01 and **:|:- p <0.001.DESCRIPTION OF SPECIFIC EMBODIMENTS OF THE INVENTIONThe present invention, in some embodiments thereof, relates to anti-insect CDA nanobodies and uses thereof.Before explaining at least one embodiment of the invention in detail, it is to be understood that the invention is not necessarily limited in its application to the details set forth in the following description or exemplified by the Examples. The invention is capable of other embodiments or of being practiced or carried out in various ways.Management of insect pests in the past 70 years has been achieved mainly through application of synthetic pesticides, most of them have a high potential for damaging the ecosystem, they are toxic to humans directly or through the food chain and their use is also impeded by development of genetic insect resistance. The most prominent biological solutions currently in use also have many disadvantages, including low efficiency, danger of violating the natural ecological balance and development genetic insect resistance.Anti-insect CDA nanobodies and their use as insecticides have also been disclosed (International Patent Application Publication No. W02021 / 095031).Whilst reducing specific embodime ts of the present invention to practice, the present inventors have now developed nanobodies targeting insect CDA having insect control activities (Examples 1 and 4 of the Examples section which follows and Tables 1-2 hereibelow). Killing was shown to be dose dependent. Consequently, specific embodiments of the present teachings suggest their use as insecticides.It will be appreciated that the nanobodies disclosed herein do not aim to encompass any of the anti-CDA nanobodies disclosed in International Patent Application Publication No. WO2021 / 095031.According to specific embodiments, the nanobodies disclosed herein have superior properties compared to other insecticidal anti-CDA targeting agents described by the prior art (e.g. nanobodies described in International Patent Application Publication No. WO2021 / 095031) such as, but not limited to, increased stability, efficacy as insecticide and / or affinity to the target.According to specific embodiments, the nanobody is not any of the nanobodies set forth in SEQ ID NOs: 166, 170, 174, 178, 182, 186, 190, 194, 198, 202, 206, 210, 214, 218, 222, 226, 230,234, 238, 242, 246, 250, 254, 258, 262, 266, 270, 274, 278, 282, 286, 290, 294, 298, 302, 306, 310,314, 318, 322, 326, 330, 331, 335, 336, 340, 344, 345, 346, 350, 354, 358, 359, 363, 367, 371, 372,376, 380, 384, 388, 392, 396, 400, 404, 408, 412, 416, 420 or 424.According to specific embodiments, the nanobody amino acid sequence has less than 70 % identity to any of the nanobodies set forth in SEQ ID NOs: 166, 170, 174, 178, 182, 186, 190, 194,198, 202, 206, 210, 214, 218, 222, 226, 230, 234, 238, 242, 246, 250, 254, 258, 262, 266, 270, 274,278, 282, 286, 290, 294, 298, 302, 306, 310, 314, 318, 322, 326, 330, 331, 335, 336, 340, 344, 345,346, 350, 354, 358, 359, 363, 367, 371, 372, 376, 380, 384, 388, 392, 396, 400, 404, 408, 412, 416,420 or 424.Sequence identity or homology can be determined using any protein or nucleic acid sequence alignment algorithm such as Blast, ClustalW, and MUSCLE.According to specific embodiments, nanobody does not comprise any of the three complementarity determining regions (CDRs) set forth in SEQ ID NOs: 167-169, 171-173, 175- 177, 179-181, 183-185, 187-189, 191-193, 195-197, 199-201, 203-205, 207-209, 211-213, 215-217, 219-221, 223-225, 227-229, 231-233, 235-237, 239-241, 243-245, 247-249, 251-253, 255-257, 259-261, 263-265, 267-269, 271-273, 275-277, 279-281, 283-285, 287-289, 291-293, 295-597, 299-301, 303-305, 307-309, 311-313, 315-317, 319-321, 323-325, 327-329, 332-334, 337-339, 341-343, 347-349, 351-353, 355-357, 360-362, 364-366, 368-370, 373-375, 377-379, 381-383, 385-387, 389-391, 393-395, 397-399, 401-403, 405-407, 409-411, 413-415, 417-419, 421-423, or 425-427 arranged in a sequential order from N to C on the nanobody.According to specific embodiments, the nanobody’s three CDRs amino acid sequences have less than 70 % identity to the three CDRs set forth in SEQ ID NOs: 167-169, 171-173, 175- 177, 179-181, 183-185, 187-189, 191-193, 195-197, 199-201, 203-205, 207-209, 211-213, 215-217, 219-221, 223-225, 227-229, 231-233, 235-237, 239-241, 243-245, 247-249, 251-253, 255-257, 259-261, 263-265, 267-269, 271-273, 275-277, 279-281, 283-285, 287-289, 291-293, 295-597, 299-301, 303-305, 307-309, 311-313, 315-317, 319-321, 323-325, 327-329, 332-334, 337-339, 341-343, 347-349, 351-353, 355-357, 360-362, 364-366, 368-370, 373-375, 377-379, 381-383, 385-387, 389-391, 393-395, 397-399, 401-403, 405-407, 409-411, 413-415, 417-419, 421-423, and 425-427 arranged in a sequential order from N to C on the nanobody.According to specific embodiments, any of the nanobody’s CDRs amino acid sequences has less than 70 % identity to the CDRs set forth in SEQ ID NOs: 167-169, 171-173, 175-177, 179- 181, 183-185, 187-189, 191-193, 195-197, 199-201, 203-205, 207-209, 211-213, 215-217, 219-221, 223-225, 227-229, 231-233, 235-237, 239-241, 243-245, 247-249, 251-253, 255-257, 259-261, 263-265, 267-269, 271-273, 275-277, 279-281, 283-285, 287-289, 291-293, 295-597, 299-301, 303-305, 307-309, 311-313, 315-317, 319-321, 323-325, 327-329, 332-334, 337-339, 341- 343, 347-349, 351-353, 355-357, 360-362, 364-366, 368-370, 373-375, 377-379, 381-383, 385- 387, 389-391, 393-395, 397-399, 401-403, 405-407, 409-411, 413-415, 417-419, 421-423, or 425- 427 arranged in a sequential order from N to C on the nanobody.Thus, according to an aspect of the present invention, there is provided a nanobody which specifically binds to an insect CD A, said nanobody comprises three complementarity determining regions (CDRs) as set forth in SEQ ID NOs: 3-5, 7-9, 11-13, 15-17, 19-21, 23-25, 27-29, 31-33, 35-37, 39-41, 43-45, 47-49, 51-53, 55-57, 59-61, 63-65, 67-69, 71-73, 75-77, 79-81, 83-85, 87- 89, 91-93, 95-97, 99-101, 103-105, 107-109, 111-113, 115-117, 119-121, 123-125, 127-129, 131- 133, 135-137, 139-141, 143-145, 147-149, 151-153, 155-157, or 159-161 arranged in a sequential order from N to C on said nanobody, wherein binding of said nanobody to said insect CDA confers an insect control activity to said nanobody.According to an additional or an alternative aspect of the present invention, there is provided a composition comprising a nanobody which specifically binds to an insect CDA, and a toxin moiety having an insect control activity, wherein said nanobody comprises three complementarity determining regions (CDRs) as set forth in SEQ ID NOs: 3-5, 7-9, 11-13, 15-17, 19-21, 23-25, 27-29, 31-33, 35-37, 39-41, 43-45, 47-49, 51-53, 55-57, 59-61, 63-65, 67-69, 71-73, 75-77, 79-81, 83-85, 87-89, 91-93, 95-97, 99-101, 103-105, 107-109, 111-113, 115-117, 119-121, 123-125, 127-129, 131-133, 135-137, 139-141, 143-145, 147-149, 151-153, 155-157, or 159-161 arranged in a sequential order from N to C on said nanobody.Epitope maddping analysis (Example 2 of the Examples section which follows) indicated the anti-CDA nanobody CDA-SF-1D (SEQ ID NO: 14) binds a non-linear epitope of Spodoptera frugiperda CDA (SEQ ID NO: 1) which comprises amino acids: ASP(D)170, ASP(D)175, GLU(E)360, ASP(D)361, ASP(D)365, ASP(D)384, TYR(Y)387, ASN(N)388, ASN(N)391, HIS(H)392, ASP(D)395, TYR(Y)398, GLU(E)399, GLU(E)419, GLU(E)422, GLU(E)430, SER(S)433 and SER(S)434; wherein the CRD3 region of the nanobody binds to GLU(E)360, ASP(D)361, ASP(D)365, ASP(D)384, HIS(H)392, GLU(E)419 and GLU(E)422 .Hence, according to an aspect of the present invention, there is provided a nanobody which specifically binds to a non-linear epitope of insect CDA, said non-linear epitope comprises an amino acid residue selected from the group consisting of D170, D175, E360, D361, D365, D384, Y387, N388, N391, H392, D395, Y398, E399, E419, E422, E430, S433 and S434 of SEQ ID NO: 1 or the corresponding amino acid residue in orthologous polypeptides, wherein binding of said nanobody to said insect CDA confers an insect control activity to said nanobody.According to an additional or an alternative aspect of the present invention, there is provided a composition comprising a nanobody which specifically binds to a non-linear epitope of insect CDA, and a toxin moiety having an insect control activity, wherein said non-linear epitope comprises an amino acid residue selected from the group consisting of D170, D175, E360, D361, D365, D384, Y387, N388, N391, H392, D395, Y398, E399, E419, E422, E430, S433 and S434 of SEQ ID NO: 1 or the corresponding amino acid residue in orthologous polypeptides.Epitope maddping analysis (Example 3 of the Examples section which follows) indicated the anti-CDA nanobody CDA-SF-2C (SEQ ID NO: 82) binds a non-linear epitope of Spodoptera frugiperda CDA (SEQ ID NO: 1) which comprises amino acids: V22, E23, L24, C25, D46, 148, 168, E99, P100, L101, C102, R286, A287, G293, G294, N295, N296, Q297, M301, E302, E3O3, Q304, L307, Y3O8, D309, S310, T311, 1312, P319, P320, P323, Y 324, T325, Y327, F328, H332, R333, C334, H335, G336, N337, L338, Q339, S340, C341, P342, T343, R344, W349, E350, M351, V352, N354, E355, D357, R358, E360, P362, N364, E366, M373, V374, D375, N391, H392, D395, Y398, E399, A403, P404, L405, G406, R415, S434, M443, T444, Q445, V446, 1447, Q448, P475, C477, W478, V479, P480, S482, C483, K484, L485, T499, C500, V501, R502, P508, L510, N511, D512, D516, G517, H518 and Y519; wherein the CRD3 region of the nanobody binds to E350, M351 and V352.Hence, according to an aspect of the present invention, there is provided a nanobody which specifically binds to a non-linear epitope of insect CDA, said non-linear epitope comprises an amino acid residue selected from the group consisting of V22, E23, L24, C25, D46, 148, 168, E99, P100, L101, C102, R286, A287, G293, G294, N295, N296, Q297, M301, E302, E303, Q304, L307, Y308, D309, S310, T311, 1312, P319, P320, P323, Y 324, T325, Y327, F328, H332, R333, C334, H335, G336, N337, L338, Q339, S340, C341, P342, T343, R344, W349, E350, M351, V352, N354, E355, D357, R358, E360, P362, N364, E366, M373, V374, D375, N391, H392, D395, Y398, E399, A403, P404, L405, G406, R415, S434, M443, T444, Q445, V446, 1447, Q448, P475, C477, W478, V479, P480, S482, C483, K484, L485, T499, C500, V501, R502, P508, L510, N511, D512, D516, G517, H518 and Y519 of SEQ ID NO: 1 or the corresponding amino acid residue in orthologous polypeptides, wherein binding of said nanobody to said insect CDA confers an insect control activity to said nanobody.According to an additional or an alternative aspect of the present invention, there is provided a composition comprising a nanobody which specifically binds to a non-linear epitope of insect CDA, and a toxin moiety having an insect control activity, wherein said non-linear epitope comprises an amino acid residue selected from the group consisting of V22, E23, L24, C25, D46, 148, 168, E99, P100, L101, C102, R286, A287, G293, G294, N295, N296, Q297, M301, E302,E303, Q304, L307, Y308, D309, S310, T311, 1312, P319, P320, P323, Y 324, T325, Y327, F328, H332, R333, C334, H335, G336, N337, L338, Q339, S340, C341, P342, T343, R344, W349, E350, M351, V352, N354, E355, D357, R358, E360, P362, N364, E366, M373, V374, D375, N391, H392, D395, Y398, E399, A403, P404, L405, G406, R415, S434, M443, T444, Q445, V446, 1447, Q448, P475, C477, W478, V479, P480, S482, C483, K484, L485, T499, C500, V501, R502, P508, L510, N511, D512, D516, G517, H518 and Y519 of SEQ ID NO: 1 or the corresponding amino acid residue in orthologous polypeptides.Following, analysis of the Spodoptera frugiperda CDA sequence in NCBI in combination with BLAST showed that both nanobody CDA-SF-1D (SEQ ID NO: 14) and nanobody CDA-SF- 2C (SEQ ID NO: 82) bind non-linear amino acid residues in the catalytic and / or chitin binding domain of CDA (Examples 2-3 of the Examples section which follows).Thus, according to an aspect of the present invention there is provided a nanobody which specifically binds to a non-linear epitope of insect CDA, said non-linear epitope is in the catalytic and / or chitin binding domain of said insect CDA, wherein binding of said nanobody to said insect CDA confers an insect control activity to said nanobody.According to an additional or an alternative aspect of the present invention, there is provided a composition comprising a nanobody which specifically binds to a non-linear epitope of insect CDA, said non-linear epitope is in the catalytic and / or chitin binding domain of said insect CDA, and a toxin moiety having an insect control activity.As used herein, the term “nanobody” refers to a single-domain antigen binding fragment.According to a specific embodiment, the nanobody is a single variable domain derived from naturally occurring heavy chain of an antibody. Nanobodies are usually derived from heavy chain only antibodies (devoid of light chains) seen in camelids (Hamers-Casterman et al., 1993, Nature 363: 446-448; Desmyter et al., 1996, Nat. Struct. Biol. 803-811) and consequently are often referred to as VHH antibody, VHH sequence or immunoglobulin single variable domain (ISVD). Camelids comprise old world camelids (Camelus bactrianus and Camelus dromedarius) and new world camelids (for example, Lama paccos, Lama glama, Lama guanicoe and Lama vicugna). Non-limiting examples of camelids include dromedary camels, Bactrian camels, wild Bactrian camels, llamas, alpacas, vicunas, and guanacos. According to specific embodiments, the camelid is a llama.NANOBODY ® and NANOBODIES® are registered trademarks of Ablynx NV (Belgium).For a further description of VHH's or Nanobodies, reference is made to the book “Single domain antibodies,” Methods in Molecular Biology, Eds. Saerens and Muyldermans, 2012, Vol. 911, in particular to the Chapter by Vincke and Muyldermans (2012), as well as to a non- limitinglist of patent applications, which are mentioned as general background art, and include: WO 94 / 04678, WO 95 / 04079, WO 96 / 34103 of the Vrije Universiteit Brussel; WO 94 / 25591, WO 99 / 37681, WO 00 / 40968, WO 00 / 43507, WO 00 / 65057, WO 01 / 40310, WO 01 / 44301, EP 1 134 231 and WO 02 / 48193 of Unilever; WO 97 / 49805, WO 01 / 21817, WO 03 / 035694, WO 03 / 054016 and WO 03 / 055527 of the Vlaams Instituut voor Bio technologic (VIB); WO 04 / 041867, WO 04 / 041862, WO 04 / 041865, WO 04 / 041863, WO 04 / 062551, WO 05 / 044858, WO 06 / 40153, WO 06 / 079372, WO 06 / 122786, WO 06 / 122787 and WO 06 / 122825, by Ablynx N.V. and the further published patent applications by Ablynx N.V. As will be known by the person skilled in the art, the nanobodies are particularly characterized by the presence of one or more Camelidae “hallmark residues” in one or more of the framework sequences (according to Kabat numbering), as described, for example, in WO 08 / 020079, on page 75, Table A-3, incorporated herein by reference.According to a specific embodiment, the nanobody refers to an intact molecule (i.e. comprising 4 frameworks regions and 3 complementarity-determining regions) or a functional fragment thereof capable of binding to an epitope of the antigen to which the intact molecule binds.As used herein, the term "epitope" refers to any antigenic determinant on an antigen to which the paratope of a nanobody binds. Epitopic determinants usually consist of chemically active surface groupings of molecules such as amino acids or carbohydrate side chains and usually have specific three-dimensional structural characteristics, as well as specific charge characteristics. An epitope may be linear or non-linear, as further described hereinbeblow.According to specific embodiments, the epitope is within the catalytic domain of CDA.According to specific embodiments, the epitope is within the chitin binding domain of CDA.According to specific embodiments, the nanobody is a whole or intact nanobody.According to specific embodiments, the nanobody is a nanobody fragment.According to specific embodiments, the size of the nanobody is 5-30 kDa, 10 - 30 kDa or 10 -20 kDa.According to specific embodiments, the size of the nanobody is about 15 kDa.The term “nanobody” also encompasses natural or synthetic analogs, homologous, mutants and variants of a nanobody.Generally, intact nanobodies comprise three complementarity-determining regions (CDRs) (CDR1; CDR2; and CDR3).As used herein, the terms "complementarity-determining region" or "CDR" are used interchangeably to refer to the antigen binding regions found within the variable region of the heavychain polypeptide. The identity of the amino acid residues in a particular nanobody that make up a CDR can be determined using methods well known in the art and include methods such as sequence variability as defined by Kabat et al. (See, e.g., Kabat et al., 1992, Sequences of Proteins of Immunological Interest, 5th ed., Public Health Service, NIH, Washington D.C.), as applied to VHH domains from Camelids in the article of Riechmann and Muyldermans (1999), location of the structural loop regions as defined by Chothia et al. (see, e.g., Chothia et al., Nature 342:877-883, 1989.), a compromise between Kabat and Chothia using Oxford Molecular's AbM antibody modeling software (now Accelrys®, see, Martin et al., 1989, Proc. Natl Acad Sci USA. 86:9268; and world wide web site www(dot)bioinf-org(dot)uk / abs), available complex crystal structures as defined by the contact definition (see MacCallum et al., J. Mol. Biol. 262:732-745, 1996) and the "conformational definition" (see, e.g., Makabe et al., Journal of Biological Chemistry, 283:1156- 1166, 2008).As used herein, the "CDRs" may refer to CDRs defined by any approach known in the art, including combinations of approaches.According to specific embodiments, the CDR is as defined by Kabat et al. as applied to VHH domains from Camelids in the article of Riechmann and Muyldermans (1999).The nanobody may be mono- specific (capable of recognizing one epitope or protein), bispecific (capable of binding two epitopes or proteins) or multi- specific (capable of recognizing multiple epitopes or proteins).According to specific embodiments, the nanobody is a mono-specific nanobody.According to specific embodiments, the nanobody is a multi- specific e.g. bi-specific, trispecific, tetra-specific.According to specific embodiments, the nanobody is a bi-specific nanobody. Methods of generating bi-specific nanobodies are known in the art and disclosed e.g., in Deffar K, Shi H, Li L, Wang X, Zhu X (2009) Afr J Biotechnol 8(12):2645-2652); and Zhu, Y. et al. (2017). Scientific reports, 7(1), 2602; the contents of which are fully incorporated herein by reference.The nanobodies disclosed herein specifically bind an insect CDA.Preferably, the nanobody specifically binds at least one epitope of an insect CDA.Assays for testing binding are well known in the art and include, but not limited to ELISA, radioimmunoassays (RIA), flow cytometry, BiaCore, bio-layer interferometry Blitz® assay, HPLC.According to specific embodiments, the nanobody binds the insect CDA with a Kd < 10“6M, <10’7M, <1(C M, < IO’9M, each possibility represents a separate embodiment of the present invention.According to specific embodiments, the nanobody is capable of binding insect CDA under open field or controlled conditions, e.g., greenhouse.The term "insect" is used herein in the broad popular sense and includes all species of the superphylum Panarthropoda (classification Systema Naturae, Brands, S.J. (comp.) 1989-2005. Systema Naturae 2000. Amsterdam, The Netherlands, [www(dot)sn2000(dot)taxonomy(dot)nl / ]), including the phyla Arthropoda, Tardigrada and Onychophora; and includes all the different phases of the life cycle, such as, but not limited to eggs, larvae, nymphs, pupae and adults. According to specific embodiments, the insect belongs to the phylum Arthropoda (including, but not limited to the orders Lepidoptera, Hemiptera, Archaeognatha, Thysanura, Paleoptera and Neoptera, also ticks, mites and spiders), even more preferably to the class Insecta.According to specific embodiments, the insect belongs to the order Lepidoptera.According to specific embodiments, the insect belongs to the order Hemiptera.Non-limiting examples of insects include moths, aphids, whitefly, bedbugs, house flies, beetles, grasshoppers, caterpillars, mosquitos, fleas, horseflies, hornets, cockroaches and ants, such as, but not limited to:• from the order Lepidoptera, for example: Acleris spp. ,Adoxophyes spp., Agrotis spp., Alabama argillacea, Amyelois spp., Anticarsia gemmatalis, Archips spp., Argyrotaenia spp., Autographa spp., Busseola fusca, Cadra cautella, Carposina nipponensis, Chilo suppressalis, Chilo spp., Choristoneura conflictana, Choristoneura fumiferana, Choristoneura occidentalis, Choristoneura rosaceana, Choristoneura spp., Clysia ambiguella, Cnaphalocrocis spp., Cnephasia spp., Cochylis spp., Coleophora spp., Crocidolomia binotalis, Cryptophlebia leucotr ta, Cydalima perspectalis, Cydia inopinata, Cydia spp., Diatraea spp., Diparopsis castanea, Earias spp., Ephestia spp., Eucosma spp., Eupoecilia ambiguella, Euproctis spp., Euxoa spp., Grapholita prunivora, Grapholita spp., Iledya nubiferanal, Helicoverpa armigera, Helicoverpa zea, Helicoverpa spp., Heliothis spp., Hellula undalis, Hyphantria cunea, Keiferia lycopersicella, Leucoptera scitella, Lithocolletis spp., Lobesia botrana, Lymantria spp., Lyonetia spp., Malacosoma spp., Mamestra brassicae, Manduca sexta, Numonia pyrivorella, Operophtera spp., Opogona sacchari, Ostrinia nubilalis, Pammene spp., Pandemis spp., Panolis flammea, Paysandisia archon, Pectinophora gossypiella, Phthorimaea operculella, Phyllonorycter spp., Pieris rapae, Pieris spp., Platynota rostrana, Plutella xylostella, Prays spp., Scirpophaga spp., Sesamia spp., Sesia spp., Sparganothis spp., Spodoptera dolichos, Spodoptera eridania, Spodoptera exigua, Spodopterafrugiperda, Spodoptera littoralis, Spodoptera litura, Spodoptera spp., Synanthedon spp., Tecia solanivora, Thaumatotibia leucotreta, Thaumetopoea processioned, Thaumetopoea spp., Tortrix spp., Trichoplusia ni, and Yponomeuta spp.; from the order Coleoptera, for example, Agrilus anxius, Agrilus planipennis, Agriotes spp., Anomala orientalis, Anoplophora chinensis, Anoplophora glabripennis, Anoplophora spp., Anthonomus bisignifer, Anthonomus eugenii, Anthonomus grandis, Anthonomus quadrigibbus, Anthonomus signatus, Anthonomus spp., Apriona spp., Arrhenodes minutus, Atomaria linearis, Chaetocnema tibialis, Conotrachelus nenuphar, Cosmopolites spp., Curculio spp., Dendroctonus micans, Dendrolimus sibiricus, Dermestes spp., Diabrotica virgifera, Diabrotica virgifera zeae, Diabrotica virgifera, Diabrotica balteata, Diabrotica barberi, Diabrotica undecimpunctata howardi, Diabrotica undecimpunctata tenella, Diabrotica undecimpunctata, Diabrotica undecimpunctata, Diabrotica spp., Epilachna varivestis, Epilachna spp., Epitrix cucumeris, Eremnus cerealis, Eremnus spp., Gonipterus scutellatus, Ips amitinus, Ips cembrae, Ips duplicatus, Ips sexdentatus, Ips typographus, Ips spp., Leptinotarsa decemlineata, Leptinotarsa juncta, Leptinotarsa texana, Lissorhoptrus spp., Listronotus bonariensis, Melolontha spp., Monochamus spp., Naupactus leucoloma, Oryzaephilus spp., Otiorhynchus spp., Phlyctinus spp., Pissodes nemorensis, Pissodes strobi, Pissodes terminalis, Pissodes spp., Popilia japonica, Popilia spp., Premnotrypes spp., Pseudopityophthorus minutissimus, Pseudopity ophthorus pruinosus, Psylliodes spp., Rhizopertha spp., Rhynchophorus ferrugineus, Rhynchophorus palmarum, Scarabaeidae family spp., Scolytidae family spp., Sitophilus spp., Sitotroga spp., Sternochetus mangiferae, Tenebrio spp., Tribolium castaneum, Tribolium spp. and Trogoderma spp.; from the order Orthoptera, for example, Gryllotalpa spp., Locusta spp., and Schistocerca spp.; from the order Blattaria, from example, Blatta spp., Blattella spp., Periplaneta spp., and Leucophaea maderae, from the order Isoptera, for example, Coptotermes spp. and Reticulitermes spp.; from the order Psocoptera, for example, Liposcelis spp.', from the order Phthiraptera, suborder Anoplura, for example, Haematopinus spp., Linognathus spp., and Pediculus spp., and Trichodectes spp.; from the order Phthiraptera, suborder Ischnocera, for example, Damalinia spp.;from the order Thysanoptera, for example, Frankliniella occidentalis, Frankliniella platensis, Frankliniella spp., Hercinothrips spp., Taeniothrips spp., Thrips palmi, Thrips tabaci, Scirtothrips aurantii, Scirtothrips citri, Scirtothrips dorsalis, and Scirtothrips spp.; from the order Hemiptera, suborder Heteroptera, for example, Cimex spp., Distantiella theobroma, Dysdercus spp., Euschistus spp., Eurygaster spp., Leptocorisa spp., Nezara spp., Piesma spp., Rhodnius spp., Sahlbergella singularis, Scotinophara spp., Triatoma spp., Miridae family spp. such as Lygus hesperus and Lygus lineoloris, Lygaeidae family spp. such as Blissus leucopterus, and Pentatomidae family spp.; from the order Hemiptera, suborder Sternorrhyncha, for example, Aleurocanthus spiniferus, Aleurocanthus woglumi, Aleurocanthus spp., Aleurothrixus floccosus, Aleyrodes brassicae, Aonidella citrina, Aonidiella spp., Aphididae family spp., Acyrthosiphon spp., Aphis fabae, Aphis glycines, Aphis gossypii, Aphis spp., Aspidiotus spp., Bemisia tabaci, Ceroplastes spp., Chrysomphalus aonidium, Chrysomphalus dictyospermi, Coccus hesperidum, Daktulosphaira vitifoliae, Diaphorina citri, Eriosoma larigerum, Gascardia spp., Lacanium corni, Lepidosaphes spp., Lopholeucaspis japonica, Macrosiphus spp., Margarodes prieskaensis, Margarodes vitis, Margarodes vredendalensis, Myzus persicae, Myzus spp., Parasaissetia nigra, Pemphigus spp., Phylloxera spp., Pianococcus spp., Pseudaulacaspis spp., Pseudococcus spp., Psylla spp., Pulvinaria aethiopica, Quadraspidiotus spp., Rhopalosiphum spp., Ripersiella hibisci, Saissetia spp., Schizaphis spp., Sitobion spp., Toxoptera citricida, Trialeurodes vaporariorum, Trioza erytreae, and Unaspis citri; from the order Hemiptera, suborder Auchenorrhyncha, for example, Circulifer haematoceps, Circulifer tenellus, Draeculacephala minerva, Empoasca spp., Erythroneura spp., Graphocephala atropunctata, Hishimonus phycitis, Myndus crudus, Laodelphax spp., Nephotettix spp., Nilaparvata spp., Scaphoideus luteolus, Scaphoideus spp., and Xyphon fulgida; from the order Hymenoptera, for example, Acromyrmex, Atta spp., Cephus spp., Diprionidae family spp. such as Diprion spp. and Gilpinia polytoma, Hoplocampa spp., Lasius spp., Monomorium pharaonis, Neodiprion spp., Formicidae family spp. such as Solenopsis spp., and Vespa spp.;• from the order Diptera, for example, Aedes albopictus, Aedes cinereus, Aedes polynesiensis, Aedes spp., Amauromyza maculosa, Anastrepha fraterculus, Anastrepha ludens, Anastrepha obliqua, Anastrepha suspensa, Anastrepha spp., Anopheles gambiae, Anopheles spp., Aschistonyx eppoi, Atherigona soccata, Bactrocera spp., Bibio hortulanus, Calliphora erythrocephala, Cephalcia lariciphila, Ceratitis rosa, Ceratitis spp., Chrysomyia spp., Culex spp., Cuterebra spp., Dacus spp., Drosophila melanogaster, Dryocosmus kuriphilus, Euphranta canadensis, Euphranta japonica, Fannia spp., Gastrophilus spp., Gilpinia hercyniae, Glossina spp., Hypoderma spp., Hippobosca spp., Liriomyza bryoniae, Liriomyza huidobrensis, Liriomyza sativae, Liriomyza trifolii, Liriomyza spp., Luc ilia spp., Melanagromyza spp., Musca spp., Oestrus spp., Orseolia spp., Oscinella frit, Pardalaspis cyanescens, Pardalaspis quinaria, Pegomyia hyoscyami, Phorbia spp., Rhagoletis pomonella, Rhagoletis spp., Sciara spp., Stomoxys spp., Tabanus spp., and Tipula spp.;• from the order Siphonaptera, for example, Ceratophyllus spp. and Xenopsylla cheopis; and• from the infraclass Thysanura, order Zygentoma, for example, Lepisma saccharina.According to specific embodiments, the insect is considered as a pest. As used herein, the term “pest" refers to an agricultural pest organism, including but not limited to whiteflies, aphids, grasshoppers, caterpillars, beetles, moths, stinkbugs, thrips, household pest organisms, such as cockroaches, ants, wasps, flies, house crickets, bed bugs, wood worms, mealworm beetles, earwigs, silverfish, termites, blood-feeding pest insects such as mosquitos, fleas and lice etc. According to specific embodiments, the insect is an agricultural pest organism.According to specific embodiments, the insect is selected from the group consisting of moth, whitefly, aphid, stinkbug, hopper, beetle and honeybee.According to specific embodiments, the insect is a sucking pest.Non-limiting examples of sucking pests include whitefly, aphid, stinkbug, hopper.According to specific emboeiments, the insect is a moth.Non-limiting Examples of moths include Helicoverpa armigera, Cydia pomonella, Spodoptera frugiperda, Mythimna unipuncta, Helicoverpa virescens, Manduca quinquemaculata, Ostrinia nubilalis and Cydia pomonella.According to specific embdodiments, the moth is Spodoptera frugiperda.According to specific embodiments, the insect is a whitefly.Non-limiting examples of whiteflies include Bemisia tabaci, Trialeurodes vaporariorum, Aleurocanthus spiniferus, Aleyrodes proletella and Dialeurodes citri.According to specific embodiments, the whitefly is Bemisia tabaci.According to specific embodiments, the Bemisia tabaci comprises B and / or Q biotypes (see e.g. by De Barro et al. (2003) Molecular Ecology Notes, 3(1), 40-43, the contents of which are fully incorporated herein by reference).According to specific embodiments, the insect is an aphid.Non-limiting examples of aphids include Myzus persicae, Aphis gossypii, Aphis fabae, Toxoptera citricida, Schizaphis graminum, Aulacorthum solani and Rhopalosiphum padi.According to specific embodiments, the aphid is Myzus persicae.As used herein, the term “specifically bind” refers to the ability of the nanobody to bind the insect CDA in a physiological environment e.g., in the insect under physiological conditions at a higher affinity compared to other polypeptides in said environment.According to specific embodiments, the nanobody binds an insect CDA with no cross reactivity with non-insect polypeptides (e.g. plant, human).According to specific embodiments, the nanobody binds an insect CDA with no cross reactivity with non-insect CDA.According to specific embodiments, the nanobody specifically binds insect CDA with no cross reactivity with other insect polypeptides.According to specific embodiments, the nanobody binds CDA of Spodoptera frugiperda with a higher affinity compared to CDA sequencese having less than 90 %, less than 80 %, less than 70 %, less that 60 %, less than 50 %, or less than 40 % homology with SEQ ID NO: 1.As used herein, “higher affinity” refers to a difference of at least 1.2 fold, at least 1.5 fold, at least 2 fold, at least 5 fold, at least 10 fold, at least 100 fold or more using the same affinity assay.According to specific emobdiments, the nanobody specifically binds CDA of Spodoptera frugiperda with no cross reactivity with CDA sequencese having less than 90 %, less than 80 %, less than 70 %, less that 60 %, less than 50 %, or less than 40 % homology with SEQ ID NO: 1.As used herein, the term “insect chitin deacetylase (CDA)” refers to the amino acid sequence of the insect enzyme E.C. No. 3.5. 1.41, an enzyme that catalyzes the conversion of chitin and H2O to chitosan and acetate, or to antigenic fragments thereof capable of eliciting a specific immune response against said fragment.Non-limiting examples of insect CDA that can be used with specific embodiments of the claimed invention include the CDA of Spodoptera exigua, Bombyx mori, Tribolium castaneum, Helicoverpa armigera (see Tables 4-5 hereinbelow).According to specific embodiments, the insect CDA is the Spodopterafrugiperda CDA, such as provided e.g. in GeneBank Accession No. XM_035590027 (SEQ ID NO: 1), XP_035444320 or XP_050561891.According to specific embodiments, the insect CDA comprises SEQ ID NO: 1.According to specific embodiments, the insect CDA consists of SEQ ID NO: 1.Typically, CDA comprises both a chitin binding domain and a catalytic domain (which catalyzes the chemical reaction).As used herein, the term “chitin binding domain” refers to an amino acid domain of insect CDA capable of binding an insect chitin (a linear polysaccharide consisting of (l->4)-beta-linked D-glucosamine residues, most of which are N-acetylated). According to specific embodiments, the chitin binding domain is peritrophin A domain.As used herein, the term “peritrophin A domain” also known as “type 2 chitin-binding domain (ChtBD2)”, pfam PF01607, refers to an amino acid sequence having six cysteines that form three disulphide bridges. According to specific embodiments, the ChtBD2 has a consensus sequence of: CX11-30CX5-6CX9-24CX12-17CX6-12C (SEQ ID NO: 428).The amino acid residues of insect CDA that constitue the chitin binding domain are known to the skilled artisan. For example, the chitin binding domain of Spodopterafrugiperda CDA is defined by amino acid residues C25 to C82 of SEQ ID NO: 1. Other non-limiting examples of chitin binding domains of CD As of other insects are provided in Tables 4-5 hereinbelow.As used herein, the term “catalycic domain” refers to an amino acid domain of insect CDA which catalyzes the conversion of chitin and H2O to chitosan and acetate.The amino acid residues of insect CDA that constitue the catalytic domain are known to the skilled artisan. For example, the catalytic domain of Spodoptera frugiperda CDA is defined by amino acid residues S345 to P453 of SEQ ID NO: 1. Other non-limiting examples of the catalytic domains of CDAs of other insects are provided in Tables 4-5 hereinbelow.According to specific embodiments, the nanobody binds to a non-linear epitope of insect CDA.As used herein, the term “non-linear epitope” also known as “conformational epitope” refers to a non-contiguous sequence of amino acids that form a three-dimensional structure within insect CDA and to which the nanobody binds.According to specific embodiments, the non-linear epitope is in the catalytic and / or the chitin binding domain of insect CDA.According to a specific embodiment, the non-linear epitope is at least in the catalytic domain of insect CDA.According to a specific embodiment, the non-linear epitope is not solely at the chitin binding domain of insect CDA.The amino acid residues of insect CDA that constitue the catalytic and chitin binding domain are known to the skilled artisan. Non-limiting examples of the catalytic and chitin binding domains of CD As of several insects are further described hereinabove and provided in Tables 4-5 hereinbelow. Further, methods of detemining the epitope to which a nanobody binds are known to the skilled in the art and include e.g. computational modeling, peptide scanning, alanine acanning, site directed mutagenesis, X-ray crystalography and NMR spectroscopy, ELISA etc.According to specific embodiments, the non-linear epitope comprises an amino acid residue selected from the group consisting of D170, D175, E360, D361, D365, D384, Y387, N388, N391, H392, D395, Y398, E399, E419, E422, E430, S433 and S434 of SEQ ID NO: 1 or the corresponding amino acid residue in orthologous polypeptides.According to specific embdoiments, the non-linear epitope comprises an amino acid residue selected from the group consisting E360, D361, D365, D384, Y387, N388, N391, H392, D395, Y398, E399, E419, E422, E430, S433 and S434 of SEQ ID NO: 1 or the corresponding amino acid residue in orthologous polypeptides.According to specific embdoiments, non-linear epitope comprises an amino acid residue selected from the group consisting of E360, D361, D365, D384, H392, E419 and E422 of SEQ ID NO: 1 or the corresponding amino acid residue in orthologous polypeptides.According to specific embodiments, the non-linear epitope comprises an amino acid residue selected from the group consisting of V22, E23, L24, C25, D46, 148, 168, E99, P100, L101, C102, R286, A287, G293, G294, N295, N296, Q297, M301, E302, E303, Q304, L307, Y308, D309, S 10, T311, 1312, P319, P320, P323, Y 324, T325, Y327, F328, H332, R333, C334, H335, G336, N337, L338, Q339, S340, C341, P342, T343, R344, W349, E350, M351, V352, N354, E355, D357, R358, E360, P362, N364, E366, M373, V374, D375, N391, H392, D395, Y398, E399, A403, P404, L405, G406, R415, S434, M443, T444, Q445, V446, 1447, Q448, P475, C477, W478, V479, P480, S482, C483, K484, L485, T499, C500, V501, R502, P508, L510, N511, D512, D516, G517, H518 and Y519 of SEQ ID NO: 1 or the corresponding amino acid residue in orthologous polypeptides.According to specific embdoiments, the non-linear epitope comprises an amino acid residue selected from the group consisting of W349, E350, M351, V352, N354, E355, D357, R358, E360, P362, N364, E366, M373, V374, D375, N391, H392, D395, Y398, E399, A403, P404, L405, G406, R415, S434, M443, T444, Q445, V446, 1447 and Q448 of SEQ ID NO: 1 or the corresponding amino acid residue in orthologous polypeptides.According to specific embdoiments, the non-linear epitope comprises an amino acid residue selected from the group consisting of is selected from the group consisting of C25, D46, 148, 168 of SEQ ID NO: 1 or the corresponding amino acid residue in orthologous polypeptides.According to specific embdoiments, the non-linear epitope comprises an amino acid residue selected from the group consisting of E350, M351 and V352 of SEQ ID NO: 1 or the corresponding amino acid residue in orthologous polypeptides.The phrase “corresponding amino acid residue in orthologous polypeptides” or "corresponding to SEQ ID NO: 1” is intended to encompass the amino acid residue as specifically identified in SEQ ID NO: 1, as well as the corresponding amino acid residue relative to any other insect CDA amino acid sequence. Methods of determining the corresponding amino acid in such polypeptides are known to the skillled in the art and include for example gene annotation databases such as NCBI in combination with a sequence alignment algorithm such as BLAST, ClustalW, MUSCLE and the like. Non-limiting examples of such polypeptides and the respective amino acid residues are provided in Tables 4-5 hereinbelow.According to specific embodiments, the amino acid residue is as specifically identified in SEQ ID NO: 1.According to other specific embodiments, the nanobody interacts with at least one, at least two, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 20, at least 25, at least 30, at least 32, at least 35, at least 40, at least 50, at least 60, at least 70, at least 80, at least 90, at least 95, at least 100 amino acid residues of CDA, as specified herein, each possibility represents a separate embodiment of the present invention.According to a specific embdoiment, the non-liner epitope comprises amino acid residues D170, D175, E360, D361, D365, D384, Y387, N388, N391, H392, D395, Y398, E399, E419, E422, E430, S433 and S434 of SEQ ID NO: 1 or the corresponding amino acid residue in orthologous polypeptides.According to a specific embdoiment, the non-liner epitope comprises amino acid residues E360, D361, D365, D384, Y387, N388, N391, H392, D395, Y398, E399, E419, E422, E430, S433 and S434 of SEQ ID NO: 1 or the corresponding amino acid residue in orthologous polypeptides.According to a specific embdoiment, the non-liner epitope comprises amino acid residues E360, D361, D365, D384, H392, E419 and E422 of SEQ ID NO: 1 or the corresponding amino acid residue in orthologous polypeptides.According to a specific embdoiment, the non-liner epitope comprises amino acid residues V22, E23, L24, C25, D46, 148, 168, E99, P100, L101, C102, R286, A287, G293, G294, N295,N296, Q297, M301, E302, E303, Q304, L307, Y3O8, D309, S310, T311, 1312, P319, P320, P323, Y 324, T325, Y327, F328, H332, R333, C334, H335, G336, N337, L338, Q339, S340, C341, P342, T343, R344, W349, E350, M351, V352, N354, E355, D357, R358, E360, P362, N364, E366, M373, V374, D375, N391, H392, D395, Y398, E399, A403, P404, L405, G406, R415, S434, M443, T444, Q445, V446, 1447, Q448, P475, C477, W478, V479, P480, S482, C483, K484, L485, T499, C500, V501, R502, P508, L510, N511, D512, D516, G517, H518 and Y519 of SEQ ID NO: 1 or the corresponding amino acid residue in orthologous polypeptides.According to a specific embdoiment, the non-liner epitope comprises amino acid residues W349, E350, M351, V352, N354, E355, D357, R358, E360, P362, N364, E366, M373, V374, D375, N391, H392, D395, Y398, E399, A403, P404, L405, G406, R415, S434, M443, T444, Q445, V446, 1447 and Q448 of SEQ ID NO: 1 or the corresponding amino acid residue in orthologous polypeptides.According to a specific embdoiment, the non-liner epitope comprises amino acid residues C25, D46, 148, 168 of SEQ ID NO: 1 or the corresponding amino acid residue in orthologous polypeptides.According to a specific embdoiment, the non-liner epitope comprises amino acid residues E350, M351 and V352 of SEQ ID NO: 1 or the corresponding amino acid residue in orthologous polypeptides.Non-limiting examples of nanobodies specifically binding insect CDA and their respective CDRs that can be used with specific embodiments of the invention are shown in Table 2 hereinbelow.According to specific embodiments, the nanobody specifically binds insect CDA and comprises three CDRs having an amino acid sequence having at least 70 %, at least 75 %, at least 80 %, at least 85 %, at least 90 %, at least 95 %, at least 96 %, at least 97 %, at least 98 %, at least 99 %, or 100 % identity to amino acid sequences as set forth in SEQ ID NOs: 3-5, 7-9, 11-13, 15- 17, 19-21, 23-25, 27-29, 31-33, 35-37, 39-41, 43-45, 47-49, 51-53, 55-57, 59-61, 63-65, 67-69, 71-73, 75-77, 79-81, 83-85, 87-89, 91-93, 95-97, 99-101, 103-105, 107-109, 111-113, 115-117, 119-121, 123-125, 127-129, 131-133, 135-137, 139-141, 143-145, 147-149, 151-153, 155-157, or 159-161 arranged in a sequential order from N to C on said nanobody, each possibility represents a separate embodiment of the present invention.According to specific embodiments, the nanobody specifically binds insect CDA and comprises three CDRs having an amino acid sequence having at least 70 %, at least 75 %, at least 80 %, at least 85 %, at least 90 %, at least 95 %, at least 96 %, at least 97 %, at least 98 %, at least99 %, or 100 % identity to amino acid sequences as set forth in SEQ ID NOs: 15-17, 83-85 or 95- 97 arranged in a sequential order from N to C on said nanobody.According to specific embodiments, the nanobody specifically binds insect CDA and comprises three CDRs having an amino acid sequence having at least 70 %, at least 75 %, at least 80 %, at least 85 %, at least 90 %, at least 95 %, at least 96 %, at least 97 %, at least 98 %, at least 99 %, or 100 % identity to amino acid sequences as set forth in SEQ ID NOs: 15-17 arranged in a sequential order from N to C on said nanobody.According to specific embodiments, the nanobody specifically binds insect CDA and comprises three CDRs having an amino acid sequence having at least 70 %, at least 75 %, at least 80 %, at least 85 %, at least 90 %, at least 95 %, at least 96 %, at least 97 %, at least 98 %, at least 99 %, or 100 % identity to amino acid sequences as set forth in SEQ ID NOs: 83-85 arranged in a sequential order from N to C on said nanobody.According to specific embodiments, the nanobody specifically binds insect CDA and comprises three CDRs as set forth in SEQ ID NOs: 3-5, 7-9, 11-13, 15-17, 19-21, 23-25, 27-29, 31-33, 35-37, 39-41, 43-45, 47-49, 51-53, 55-57, 59-61, 63-65, 67-69, 71-73, 75-77, 79-81, 83-85, 87-89, 91-93, 95-97, 99-101, 103-105, 107-109, 111-113, 115-117, 119-121, 123-125, 127-129, 131-133, 135-137, 139-141, 143-145, 147-149, 151-153, 155-157, or 159- 161 arranged in a sequential order from N to C on said nanobody, each possibility represents a separate embodiment of the present invention.According to specific embodiments, the nanobody specifically binds insect CDA and comprises three CDRs as set forth in SEQ ID NOs: 15-17, 83-85 or 95-97 arranged in a sequential order from N to C on said nanobodyAccording to specific embodiments, the nanobody specifically binds insect CDA and comprises three CDRs as set forth in SEQ ID NOs: 15-17 arranged in a sequential order from N to C on said nanobody.According to specific embodiments, the nanobody specifically binds insect CDA and comprises three CDRs as set forth in SEQ ID NOs: 83-85 arranged in a sequential order from N to C on said nanobody.According to specific embodiments, the nanobody specifically binds insect CDA and comprises three CDRs as set forth in SEQ ID NOs: 95-97 arranged in a sequential order from N to C on said nanobody.According to specific embodiments, the nanobody comprises an amino acid sequence having at least 70 %, at least 75 %, at least 80 %, at least 85 %, at least 90 %, at least 95 %, at least 96 %, at least 97 %, at least 98 %, at least 99 % or 100 % identity to an amino acid sequenceselected from the group consisting of SEQ ID NOs: 2, 6, 10, 14, 18, 22, 26, 30, 34, 38, 42, 46, 50, 54, 58, 62, 66, 70, 74, 78, 82, 86, 90, 94, 98, 102, 106, 110, 114, 118, 122, 126, 130, 134, 138, 142, and 146, each possibility represents a separate embodiment of the present invention.According to specific embodiments, the nanobody comprises an amino acid sequence having at least 70 %, at least 75 %, at least 80 %, at least 85 %, at least 90 %, at least 95 %, at least 96 %, at least 97 %, at least 98 %, at least 99 % or 100 % identity to an amino acid sequence selected from the group consisting of SEQ ID NOs: 14, 82 and 94.According to specific embodiments, the nanobody comprises an amino acid sequence having at least 70 %, at least 75 %, at least 80 %, at least 85 %, at least 90 %, at least 95 %, at least 96 %, at least 97 %, at least 98 %, at least 99 % or 100 % identity to SEQ ID NO: 14.According to specific embodiments, the nanobody comprises an amino acid sequence having at least 70 %, at least 75 %, at least 80 %, at least 85 %, at least 90 %, at least 95 %, at least 96 %, at least 97 %, at least 98 %, at least 99 % or 100 % identity to SEQ ID NO: 82.According to specific embodiments, the nanobody comprises an amino acid sequence having at least 70 %, at least 75 %, at least 80 %, at least 85 %, at least 90 %, at least 95 %, at least 96 %, at least 97 %, at least 98 %, at least 99 % or 100 % identity to SEQ ID NO: 94.According to specific embodiments, the nanobody comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 2, 6, 10, 14, 18, 22, 26, 30, 34, 38, 42, 46, 50, 54, 58, 62, 66, 70, 74, 78, 82, 86, 90, 94, 98, 102, 106, 110, 114, 118, 122, 126, 130, 134, 138, 142 and 146.According to specific embodiments, the nanobody comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 14, 82 and 94.According to specific embodiments, the nanobody comprises SEQ ID NO: 14.According to specific embodiments, the nanobody comprises SEQ ID NO: 82.According to specific embodiments, the nanobody comprises SEQ ID NO: 94.According to specific embodiments, the nanobody consists of an amino acid sequence selected from the group consisting of SEQ ID NOs: 2, 6, 10, 14, 18, 22, 26, 30, 34, 38, 42, 46, 50, 54, 58, 62, 66, 70, 74, 78, 82, 86, 90, 94, 98, 102, 106, 110, 114, 118, 122, 126, 130, 134, 138, 142, and 146.According to specific embodiments, the nanobody consists of an amino acid sequence selected from the group consisting of SEQ ID NOs: 14, 82 and 94.According to specific embodiments, the nanobody consists of SEQ ID NO: 14.According to specific embodiments, the nanobody consists of SEQ ID NO: 82.According to specific embodiments, the nanobody consists of SEQ ID NO: 94.It should be noted that the nanobodies of some embodiments of the present invention in their broadest sense are not limited to a specific biological source or to a specific method of preparation. For example, nanobodies, can generally be obtained: (1) by isolating the VHH domain of a naturally occurring heavy chain antibody; (2) by expression of a nucleotide sequence encoding a naturally occurring VHH domain; (3) by “humanization” of a naturally occurring VHH domain or by expression of a nucleic acid encoding a such humanized VHH domain; (4) by “camelization” of a naturally occurring VH domain from any animal species, and in particular from a mammalian species, such as from a human being, or by expression of a nucleic acid encoding such a camelized VH domain; (5) by “camelization” of a “domain antibody” or “Dab,” as described in the art, or by expression of a nucleic acid encoding such a camelized VH domain; (6) by using synthetic or semisynthetic techniques for preparing proteins, polypeptides or other amino acid sequences known per se; (7) by preparing a nucleic acid encoding a nanobody using techniques for nucleic acid synthesis known per se, followed by expression of the nucleic acid thus obtained; and / or (8) by any combination of one or more of the foregoing. A further description of nanobodies, including humanization and / or camelization of nanobodies, can be found, e.g., in WO 08 / 101985 and WO 08 / 142164, as well as further herein. A recently reported fully in vitro platform based on yeast surface display for nanobody discovery is disclosed in McMahon, Conor, et al. " Nature structural & molecular biology 25.3 (2018): 289.According to specific embodiments, the nanobody is “camelized.” For example, “camelization” can be performed by providing a nucleotide sequence that encodes a naturally occurring VH domain and then changing, in a manner known per se, one or more codons in the nucleotide sequence in such a way that the new nucleotide sequence encodes a “camelized” nanobody, respectively. This nucleic acid can then be expressed in a manner known per se, so as to provide the desired nanobody.Other suitable methods and techniques for obtaining the nanobody and / or nucleic acid sequence encoding same, starting from naturally occurring VH sequences or preferably VHH sequences, will be clear from the skilled person, and may, for example, comprise combining one or more parts of one or more naturally occurring VH sequences (such as one or more FR sequences and / or CDR sequences), one or more parts of one or more naturally occurring VHH sequences (such as one or more FR sequences or CDR sequences), and / or one or more synthetic or semi- synthetic sequences, in a suitable manner, so as to provide the nanobody or a nucleic acid sequence encoding same.A specific method of generating nanobodies is described herein.According to an aspect of the present invention there is provided a method of producing a nanobody, the method comprising immunizing a camelid with a recombinant or purified insect CDA as set forth in SEQ ID NO: 1, wherein purity of said insect CDA in an insect polypeptide preparation is at least 80 %.As used herein, the phrase “purified insect CDA” refers to an CDA polypeptide purified from an insect such that its purity compared to other polypeptides present in the protein preparation is at least 80 %.According to specific embodiments, the purity of the insect CDA in the purified insect protein preparation is at least 85 %, at least 90 %, at least 95 %, at least 96 %, at least 97 %, at least 98 %, at least 99 % or 100 %, each possibility represents a separate embodiment of the present invention.According to specific embodiments, the method further comprising isolating the nanobody.Methods of isolating nanobodies are well known and are disclosed e.g. in Pardon et al. Nat Protoc. 2014 Mar; 9(3): 674-693, the contents of which are fully incorporated herein by reference, and in the Examples section that follows.Once nanobodies are obtained, binding of the nanobody to the target insect CDA, the effect on the activity of the target insect CDA and / or the biological activity (e.g. insect control activity) of the nanobody can be assayed either in vivo or in vitro. Such methods are known in the art and are further disclosed hereinabove and below.Thus, according to specific embodiments, the method further comprises selecting a nanobody demonstrating an insect control activity in a biological assay. Such assays are known in the art and are further described hereinbelow.According to specific embodiments, the method comprises testing the catalytic and / or chitin binding activity of insect CDA following contacting with the nanobody.Thus, according to an additional or an latemative aspect of the present invention, there is provides a method of producing a nanobody, the method comprising:(i) immunizing a camelid with a recombinant or purified insect CDA, wherein purity of said insect CDA in an insect polypeptide preparation is at least 80 %;(ii) isoltating the nobonody following the immunizing; and(ii) testing the catalytic and / or chitin binding activity of an insect CDA following contacing with said nanobody.According to specific embodiments, the method further comprises selecting a nanobody downregulating the catalytic and / or chitin binding activity of insect CDA. Such assays are known in the art and are further described hereinbelow.According to specific embodiments, the nanobody is a naked nanobody.As used herein, the tern "naked nanobody" refers to a nanobody which does not comprise a heterologous effector moiety e.g. toxin moiety, detectable moiety.According to specific embodiments, the nanobody comprises a heterologous effector moiety e.g. toxin moiety, detectable moiety. The effector moiety can be proteinaceous or non-proteinaceous (e.g. small molecule chemical compounds); the latter generally being generated using functional groups on the nanobody and on the conjugate partner.Thus, for example, various types of detectable or reporter moieties may be conjugated to the nanobody of the invention. These include, but not are limited to, a radioactive isotope (such as

[0125] iodine), a phosphorescent chemical, a chemiluminescent chemical, a fluorescent chemical or polypeptide (e.g. phycoerythrin (PE), fluorescein isothiocyanate (FITC), Cy-chrome, rhodamine, green fluorescent protein (GFP), blue fluorescent protein (BFP), Texas red, Cy5, PE-Cy5, and the like), an enzyme (e.g. e.g., horseradish peroxidase (HPR), beta-galactosidase, and alkaline phosphatase (AP), an affinity tag [e.g. an antigen identifiable by a corresponding antibody (e.g., digoxigenin (DIG) which is identified by an anti-DIG antibody) or a molecule having a high affinity towards the tag (e.g., streptavidin and biotin)], and molecules (contrast agents) detectable by Positron Emission Tomography (PET) or Magnetic Resonance Imaging (MRI).According to specific embodiments, the nanobody comprises a toxin.As used herein, the term “toxin” or “toxin moiety” refers to a compound having an insect control activity (as defined hereinbelow) including, but not limited to, a polypeptide, a polynucleotide, a small molecule, etc.Non-limiting Examples of toxin moieties include 5-endotoxins [such as CrylA, CrylB, CrylC, CrylD, CrylE, CrylF, CrylG, CrylH, Cryll, CrylJ, CrylK, Cry2A, Cry7B, Cry8D, Cry9A, Cry9B, Cry9C, Cry9D, Cry9E, Cryl5A, Cry22A, Cry32A, Cry51A, CytlA (Crickmore et al., 1998; van Frankenhuyzen, 2009], colicins (such as colicin El, colicin la, colicin A, colicin N), actinoporins (such as equinatoxin II, sticholysin II, fragaceatoxin C), ClyA family toxins (such as cytolysin A, non-haemolytic tripartite enterotoxin, haemolysin BL), haemolysins (such as a- haemolysin, y-haemolysin, leukocidins, nectrotic enteritis toxin B, 5-toxin, Vibrio cholerae cytolysin, Vibrio vulnificus haemolysin), aerolysin family toxins (such as aerolysin, a-toxin, hydralysin, E -toxin, enterotoxin, haemolytic lectin, kysenin), cholesterol-dependent cytoly ins (such as perfringolysin, suilysin, intermedilysin, listeriolysin O, lectinolysin, anthrolysin, streptolysin), membrane attack complex components / perforins (such as Plu-MACPF, Bth- MACPF), repeats -in- toxins (such as HlyA, bifunctional haemolysin-adenylyl cyclase toxin, MARTX) (Dal Peraro and van der Goot, 2016), spider toxins, scorpion toxins, patatin, a Bacillusthuringiensis insecticidal protein, a Xenorhabdus insecticidal protein, a Photorhabdus insecticidal protein, a Bacillus laterosporous insecticidal protein, a Bacillus bombysepticus insecticidal protein, a Bacillus sphaericus insecticidal protein, and insect-controlling double-stranded RNAsThe effector moiety e.g. toxin moiety, detectable moiety may be attached or conjugated to the nanobody of the invention in various ways, depending on the context, application and purpose.The effector moiety may be coupled directly or indirectly (e.g. when comprised in a carrier) to the nanobody. The coupling can be a covalent or non-covalent binding.When the effector moiety is a polypeptide, the immunoconjugate may be produced by recombinant means. For example, the nucleic acid sequence encoding a toxin or a fluorescent protein may be ligated in-frame with the nucleic acid sequence encoding the nanobody and be expressed in a host cell to produce a recombinant conjugated antibody. Alternatively, the effector moiety may be chemically synthesized by, for example, the stepwise addition of one or more amino acid residues in defined order such as solid phase peptide synthetic techniques.An effector moiety may also be attached to the nanobody using standard chemical synthesis techniques widely practiced in the art [see e.g., worldwideweb (dot) chemistry (dot) org / portal / Chemistry)], such as using any suitable chemical linkage, direct or indirect, as via a peptide bond (when the effector moiety is a polypeptide), or via covalent bonding to an intervening linker element, such as a linker peptide or other chemical moiety, such as an organic polymer. Chimeric peptides may be linked via bonding at the carboxy (C) or amino (N) termini of the peptides, or via bonding to internal chemical groups such as straight, branched or cyclic side chains, internal carbon or nitrogen atoms, and the like. Description of fluorescent labeling is provided in details in U.S. Pat. Nos. 3,940,475, 4,289,747, and 4,376,110.Exemplary methods for conjugating peptide moieties to the nanobody include, but not limited to SPDP conjugation, Glutaraldehyde conjugation and Carbodiimide conjugation.The nanobody can also be attached to particles or carriers, which comprise the effector moiety. Methods of covalently binding a nanobody to an encapsulating particle are known in the art and disclosed for example in US Patent Nos. 5,171,578, 5,204,096 and 5,258,499.Any of the polypeptides (e.g. nanobodies and proteinaceous compositions) described herein can be encoded from a polynucleotide. These polynucleotides can be used per se or in the recombinant production of the polypeptides disclosed herein.Thus, according to an aspect of the present invention there is provided a polynucleotide encoding the nanobody or the composition comprising the nanobody and the toxin.As used herein the term “polynucleotide” refers to a single or double stranded nucleic acid sequence which is isolated and provided in the form of an RNA sequence, a complementarypolynucleotide sequence (cDNA), a genomic polynucleotide sequence and / or a composite polynucleotide sequence (e.g., a combination of the above).According to specific embodiments, any of the polynucleotides and nucleic acid sequences disclosed herein may comprise conservative nucleic acid substitutions. Conservatively modified polynucleotides refer to those nucleic acids which encode identical or essentially identical amino acid sequences, or where the nucleic acid does not encode an amino acid sequence, to essentially identical or associated (e.g., naturally contiguous) sequences. Because of the degeneracy of the genetic code, a large number of functionally identical nucleic acids encode most proteins. For instance, the codons GCA, GCC, GCG and GCU all encode the amino acid alanine. Thus, at every position where an alanine is specified by a codon, the codon can be altered to another of the corresponding codons described without altering the encoded polypeptide. Such nucleic acid variations are "silent variations", which are one species of conservatively modified polynucleotides. According to specific embodiments, any polynucleotide and nucleic acid sequence described herein, which, encodes a polypeptide also describes silent variations of the nucleic acid. One of skill will recognize that in certain contexts each codon in a nucleic acid (except AUG, which is ordinarily the only codon for methionine, and TGG, which is ordinarily the only codon for tryptophan) can be modified to yield a functionally identical molecule. Accordingly, silent variations of a polynucleotide which encodes a polypeptide is implicit in a described sequence with respect to the expression product.According to specific embodiments, the nucleic acid sequences disclosed herein are codon optimized for e.g. mammalian or plant expression.Methods of codon optimization are known in the art and disclosed e.g. in the Codon Usage Database through the NIAS (National Institute of Agrobiological Sciences) DNA bank in Japan (www(dot)kazusa(dot)or(dot)jp / codon / ); International Patent Application on. 93 / 07278; and Grote et al. Nucleic Acid Res. Nucleic Acids Res. (2005) Jul 1; 33(Web Server issue): W526-W531).Thus, some embodiments of the invention encompasse nucleic acid sequences described hereinabove; fragments thereof, sequences hybridizable therewith, sequences homologous thereto, sequences orthologous thereto, sequences encoding similar polypeptides with different codon usage, altered sequences characterized by mutations, such as deletion, insertion or substitution of one or more nucleotides, either naturally occurring or man induced, either randomly or in a targeted fashion.Non-limiting examples of polynucleotides encoding the nanobody of some embodiments of the invention are provided in SEQ ID NOs: 429-468.To express an exogenous polypeptide in a cell, a polynucleotide sequence encoding the polypeptide is preferably ligated into a nucleic acid construct suitable for expression in the cell. Such a nucleic acid construct includes a promoter sequence for directing transcription of the polynucleotide sequence in the cell in a constitutive or inducible manner.Hence, according to an aspect of the present invention there is provided a nucleic acid construct comprising the polynucleotide and a cis-acting regulatory element for directing expression of said polynucleotide.According to specific embodiments, the regulatory element is a heterologous regulatory element.The nucleic acid construct (also referred to herein as an "expression vector") of some embodiments of the invention includes additional sequences which render this vector suitable for replication and integration in prokaryotes, eukaryotes, or preferably both (e.g., shuttle vectors). In addition, typical cloning vectors may also contain a transcription and translation initiation sequence, transcription and translation terminator and a polyadenylation signal. By way of example, such constructs will typically include a 5' LTR, a tRNA binding site, a packaging signal, an origin of second-strand DNA synthesis, and a 3' LTR or a portion thereof.The nucleic acid construct of some embodiments of the invention typically includes a signal sequence for secretion of the polypeptide from a cell in which it is placed. According to specific embodiments, the signal sequence is the native signal sequence of the polypeptide (e.g. nanobody) of some embodiments of the invention.Eukaryotic promoters typically contain two types of recognition sequences, the TATA box and upstream promoter elements. The TATA box, located 25-30 base pairs upstream of the transcription initiation site, is thought to be involved in directing RNA polymerase to begin RNA synthesis. The other upstream promoter elements determine the rate at which transcription is initiated.Preferably, the promoter utilized by the nucleic acid construct of some embodiments of the invention is active in the specific cell population transformed. Examples of cell type-specific and / or tissue-specific promoters include promoters such as albumin that is liver specific [Pinkert et al., (1987) Genes Dev. 1:268-277], lymphoid specific promoters [Calame et al., (1988) Adv. Immunol. 43:235-275]; in particular promoters of T-cell receptors [Winoto et al., (1989) EMBO J. 8:729-733] and immunoglobulins; [Banerji et al. (1983) Cell 33729-740], pancreas-specific promoters [Edlunchet al. (1985) Science 230:912-916] or mammary gland- specific promoters such as the milk whey promoter (U.S. Pat. No. 4,873,316 and European Application Publication No. 264,166).In cases where plant expression vectors are used, the expression of the coding sequence can be driven by a number of promoters. For example, viral promoters such as the 35S RNA and 19S RNA promoters of CaMV [Brisson et al. (1984) Nature 310:511-514], or the coat protein promoter to TMV [Takamatsu et al. (1987) EMBO J. 6:307-311] can be used. Alternatively, plant promoters such as the small subunit of RUBISCO [Coruzzi et al. (1984) EMBO J. 3:1671-1680 and Brogli et al., (1984) Science 224:838-843], include AlcR / AlcA (ethanol inducible); GR fusions, GVG, and pOp / LhGR (dexamethasone inducible); XVE / OlexA (beta-estradiol inducible); or heat shock promoters, e.g., soybean hspl7.5-E or hspl7.3-B [Gurley et al. (1986) Mol. Cell. Biol. 6:559-565] can be used.Enhancer elements can stimulate transcription up to 1,000 fold from linked homologous or heterologous promoters. Enhancers are active when placed downstream or upstream from the transcription initiation site. Many enhancer elements derived from viruses have a broad host range and are active in a variety of tissues. For example, the SV40 early gene enhancer is suitable for many cell types. Other enhancer / promoter combinations that are suitable for some embodiments of the invention include those derived from polyoma virus, human or murine cytomegalovirus (CMV), the long terminal repeat from various retroviruses such as murine leukemia virus, murine or Rous sarcoma virus and HIV. See, Enhancers and Eukaryotic Expression, Cold Spring Harbor Press, Cold Spring Harbor, N.Y. 1983, which is incorporated herein by reference. Enhancers specific for distinct neuronal cell types that can be included in AAV expression vectors to gain specificity without a Cre-driver line have also been described in the arts and described e.g. in Hrvatin et al. (doi: www(dot)doi(dot)org / 10.1101 / 570895), which is incorporated herein by reference.In the construction of the expression vector, the promoter is preferably positioned approximately the same distance from the heterologous transcription start site as it is from the transcription start site in its natural setting. As is known in the art, however, some variation in this distance can be accommodated without loss of promoter function.Polyadenylation sequences can also be added to the expression vector in order to increase the efficiency of mRNA translation. Two distinct sequence elements are required for accurate and efficient polyadenylation: GU or U rich sequences located downstream from the poly adenylation site and a highly conserved sequence of six nucleotides, AAUAAA, located 11-30 nucleotides upstream. Termination and polyadenylation signals that are suitable for some embodiments of the invention include those derived from SV40.In addition to the elements already described, the expression vector of some embodiments of the invention may typically contain other specialized elements intended to increase the level ofexpression of cloned nucleic acids or to facilitate the identification of cells that carry the recombinant DNA. For example, a number of animal viruses contain DNA sequences that promote the extra chromosomal replication of the viral genome in permissive cell types. Plasmids bearing these viral replicons are replicated episomally as long as the appropriate factors are provided by genes either carried on the plasmid or with the genome of the host cell.The vector may or may not include a eukaryotic replicon. If a eukaryotic replicon is present, then the vector is amplifiable in eukaryotic cells using the appropriate selectable marker. If the vector does not comprise a eukaryotic replicon, no episomal amplification is possible. Instead, the recombinant DNA integrates into the genome of the engineered cell, where the promoter directs expression of the desired nucleic acid.The expression vector of some embodiments of the invention can further include additional polynucleotide sequences that allow, for example, the translation of several proteins from a single mRNA such as an internal ribosome entry site (IRES) and sequences for genomic integration of the promoter-chimeric polypeptide.It will be appreciated that the individual elements comprised in the expression vector can be arranged in a variety of configurations. For example, enhancer elements, promoters and the like, and even the polynucleotide sequence(s) encoding the polypeptide can be arranged in a "head- to-tail" configuration, may be present as an inverted complement, or in a complementary configuration, as an anti-parallel strand. While such variety of configuration is more likely to occur with non-coding elements of the expression vector, alternative configurations of the coding sequence within the expression vector are also envisioned.Examples for mammalian expression vectors include, but are not limited to, pcDNA3, pcDN A3. 1 (+ / -), pGL3, pZeoSV2(+ / -), pSecTag2, pDisplay, pEF / myc / cyto, pCMV / myc / cyto, pCR3.1, pSinRep5, DH26S, DHBB, pNMTl, pNMT41, pNMT81, which are available from Invitrogen, pCI which is available from Promega, pMbac, pPbac, pBK-RSV and pBK-CMV which are available from Strategene, pTRES which is available from Clontech, and their derivatives.Expression vectors containing regulatory elements from eukaryotic viruses such as retroviruses can be also used. SV40 vectors include pSVT7 and pMT2. Vectors derived from bovine papilloma virus include pBV-lMTHA, and vectors derived from Epstein Bar virus include pHEBO, and p2O5. Other exemplary vectors include pMSG, pAV009 / A+, pMTO10 / A+, pMAMneo-5, baculovirus pDSVE, and any other vector allowing expression of proteins under the direction of the SV-40 early promoter, SV-40 later promoter, metallothionein promoter, murine mammary tumor virus promoter, Rous sarcoma virus promoter, polyhedrin promoter, or other promoters shown effective for expression in eukaryotic cells.As described above, viruses are very specialized infectious agents that have evolved, in many cases, to elude host defense mechanisms. Typically, viruses infect and propagate in specific cell types. The targeting specificity of viral vectors utilizes its natural specificity to specifically target predetermined cell types and thereby introduce a recombinant gene into the infected cell. Thus, the type of vector used by some embodiments of the invention will depend on the cell type transformed. The ability to select suitable vectors according to the cell type transformed is well within the capabilities of the ordinary skilled artisan and as such, no general description of selection consideration is provided herein.The cells may be transformed stably or transiently with the nucleic acid constructs of some embodiments of the invention. In stable transformation, the nucleic acid molecule of some embodiments of the invention is integrated into the cell genome and as such it represents a stable and inherited trait. In transient transformation, the nucleic acid molecule is expressed by the cell transformed but it is not integrated into the genome and as such, it represents a transient trait.Various methods can be used to introduce the expression vector of some embodiments of the invention into cells. Such methods are generally described in Sambrook et al., Molecular Cloning: A Laboratory Manual, Cold Springs Harbor Laboratory, New York (1989, 1992), in Ausubel et al., Current Protocols in Molecular Biology, John Wiley and Sons, Baltimore, Md. (1989), Chang et al., Somatic Gene Therapy, CRC Press, Ann Arbor, Mich. (1995), Vega et al., Gene Targeting, CRC Press, Ann Arbor Mich. (1995), Vectors: A Survey of Molecular Cloning Vectors and Their Uses, Butterworths, Boston Mass. (1988) and Gilboa et at. [Bio techniques 4 (6): 504-512, 1986] and include, for example, stable or transient transfection, lipofection, electroporation and infection with recombinant viral vectors. In addition, see U.S. Pat. Nos. 5,464,764 and 5,487,992 for positive-negative selection methods.In cases where plant expression vectors are used, the constructs can be introduced into plant cells using Ti plasmid, Ri plasmid, plant viral vectors, direct DNA transformation, microinjection, electroporation and other techniques well known to the skilled artisan. See, for example, Weissbach & Weissbach, 1988, Methods for Plant Molecular Biology, Academic Press, NY, Section VIII, pp 421-463.Introduction of nucleic acids by viral infection offers several advantages over other methods such as lipofection and electroporation, since higher transfection efficiency can be obtained due to the infectious nature of viruses.Currently preferred in vivo nucleic acid transfer techniques include transfection with viral or non-viral constructs, such as adenovirus, lentivirus, Herpes simplex I virus, or adeno-associated virus (AAV) and lipid-based systems. Useful lipids for lipid-mediated transfer of the gene are, forexample, DOTMA, DOPE, and DC-Chol [Tonkinson et al., Cancer Investigation, 14(1): 54-65 (1996)]. The most preferred constructs for use in gene therapy are viruses, most preferably adenoviruses, AAV, lentiviruses, or retroviruses. A viral construct such as a retroviral construct includes at least one transcriptional promoter / enhancer or locus -defining element(s), or other elements that control gene expression by other means such as alternate splicing, nuclear RNA export, or post-translational modification of messenger. Such vector constructs also include a packaging signal, long terminal repeats (LTRs) or portions thereof, and positive and negative strand primer binding sites appropriate to the virus used, unless it is already present in the viral construct. In addition, such a construct typically includes a signal sequence for secretion of the peptide from a host cell in which it is placed. Preferably, the signal sequence for this purpose is a mammalian signal sequence or the signal sequence of the polypeptide variants of some embodiments of the invention. Optionally, the construct may also include a signal that directs polyadenylation, as well as one or more restriction sites and a translation termination sequence. By way of example, such constructs will typically include a 5' LTR, a tRNA binding site, a packaging signal, an origin of second-strand DNA synthesis, and a 3' LTR or a portion thereof. Other vectors can be used that are non- viral, such as cationic lipids, polylysine, and dendrimers.Other than containing the necessary elements for the transcription and translation of the inserted coding sequence, the expression construct of some embodiments of the invention can also include sequences engineered to enhance stability, production, purification, yield or toxicity of the expressed peptide. For example, the expression of a fusion protein or a cleavable fusion protein comprising the polypeptide of some embodiments of the invention and a heterologous protein can be engineered. Such a fusion protein can be designed so that the fusion protein can be readily isolated by affinity chromatography; e.g., by immobilization on a column specific for the heterologous protein. Where a cleavage site is engineered between the polypeptide and the heterologous protein, the polypeptide can be released from the chromatographic column by treatment with an appropriate enzyme or agent that disrupts the cleavage site [e.g., see Booth et al. (1988) Immunol. Lett. 19:65-70; and Gardella et al., (1990) J. Biol. Chem. 265:15854-15859].The present invention also contemplates cells comprising the polypeptides, polynucleotides and nucleic acid constructs described herein.Thus, according to an aspect of the present invention there is provided a host cell comprising the nanobody or the composition comprising the nanobody and the toxin or a polynucleotide or a nucleic acid construct encoding same.As mentioned hereinabove, a variety of prokaryotic or eukaryotic cells can be used as hostexpression systems to express the polypeptides of some embodiments of the invention. Theseinclude, but are not limited to, microorganisms, such as bacteria transformed with a recombinant bacteriophage DNA, plasmid DNA or cosmid DNA expression vector containing the coding sequence; yeast transformed with recombinant yeast expression vectors containing the coding sequence; plant cell systems infected with recombinant virus expression vectors (e.g., cauliflower mosaic virus, CaMV; tobacco mosaic virus, TMV) or transformed with recombinant plasmid expression vectors, such as Ti plasmid, containing the coding sequence. Mammalian expression systems can also be used to express the polypeptides of some embodiments of the invention.According to specific embodiments, the cell is a mammalian cell.According to specific embodiments, the cell is a camelid cell.Suitable mammalian cells include primary cells and immortalized cell lines.According to other specific embodiments, the mammalian cell is an immortalized cell line.Suitable mammalian cell lines include, but are not limited to, HeLa cells (e.g., American Type Culture Collection (ATCC) No. CCL-2), CHO cells (e.g., ATCC Nos. CRL9618, CCL61, CRL9096), HEK293 cells (e.g., ATCC No. CRL-1573), Vero cells, NIH 3T3 cells (e.g., ATCC No. CRL-1658), Huh-7 cells, BHK cells (e.g., ATCC No. CCL10), PC12 cells (ATCC No. CRL1721), COS cells, COS-7 cells (ATCC No. CRL1651), RATI cells, mouse Lcells (ATCC No. CCLI.3), human embryonic kidney (HEK) cells (ATCC No. CRL1573), HLHepG2 cells, NSO, Sp2 / 0, BHK, Namalwa, and the like.According to specific embodiments, the cell is E. coli e.g. SHuffle T7 Express & BL21.According to specific embodiments, the cell is a plant cell.According to an aspect of the present invention there is provided a method of producing an insect control nanobody, the method comprising expressing in a host cell the polynucleotide or the nucleic acid construct disclosed herein.According to an additional or an alternative aspect of the present invention there is provided a method of producing an insect control nanobody, the method comprising introducing the polynucleotide or nucleic acid construct encoding the insect control nanobody disclosed herein to a host cell.According to an additional or an alternative aspect of the present invention there is provided a method of producing an insect control nanobody, the method comprising culturing the cell comprising the insect control nanobody disclosed herein or a polynucleotide or a nucleic acid construct encoding it.According to specific embodiments, the expressing, introducing and / or culturing is effected under conditions which allow expression of the insect control nanobody.Such conditions may be for example an appropriate temperature (e.g., 37 °C), atmosphere (e.g., air plus 5 % CO2), pH, light, medium, supplements and the like.According to specific embodiments, the expressing and / or introducing is effected in-vitro or ex-vivo.According to specific embodiments, the method further comprising isolating the nanobody.Isolation or recovery of any of the recombinant polypeptides (e.g. nanobody) may be effected by any method known in the art. According to specific embodiments, recovery or isolation of the recombinant polypeptide is effected following an appropriate time in culture. The phrase "recovering the recombinant polypeptide” or “isolating the recombinant polypeptide” refers to collecting the whole fermentation medium containing the polypeptide and need not imply additional steps of separation or purification. Notwithstanding the above, polypeptides of some embodiments of the invention can be purified using a variety of standard protein purification techniques, such as, but not limited to, affinity chromatography, ion exchange chromatography, filtration, electrophoresis, hydrophobic interaction chromatography, gel filtration chromatography, reverse phase chromatography, concanavalin A chromatography, mix mode chromatography, metal affinity chromatography, Lectins affinity chromatography chromatofocusing and differential solubilization.According to specific embodiments, following synthesis and purification, the binding and / or the insect control activity of the nanobody can be assayed either in vivo or in vitro. Such methods are known in the art and are further disclosed hereinabove and below.The compositions disclosed herein (e.g. the nanobodies, the composition comprising the nanobody and the toxin, polynucleotides and nucleic acid constructs encoding same and host cells expressing same) may be formulated in an appropriate means such as lyophilized, freeze-dried, desiccated, or in an aqueous carrier, medium or suitable diluent, such as saline or another buffer. According to specific embodiments, the formulated compositions may be in the form of a dust or granular material, powder, gel, cream, paste, pellet, tablet or a suspension in oil (vegetable or mineral), or water or oil / water emulsions, capsule suspension, emulsifiable concentrate, or as a wettable powder, wettable granules, water dispersible granules, aerosols, foam, slurries or flowable concentrates.According to specific embodiments, the composition is formulated as a liquid concentrate, dry powder, tablet, capsule suspension, slurry or "wet cake", which can be suitably diluted, dispersed, suspended, emulsified or otherwise suitably reconstituted by the end user prior to final use.According to specific embodiments, the composition is formulated as a liquid formulation.According to specific embodiments, the composition is formulated as a dry formulation.According to specific embodiments, the composition is formulated for delivery by spraying, irrigation and / or fumigation.According to specific embodiments, the compositions disclosed herein (e.g. the nanobodies, the composition comprising the nanobody and the toxin, polynucleotides and nucleic acid constructs encoding same and host cells expressing same) are stable, both during storage and during utilization, meaning that the integrity of the composition is maintained under storage and / or utilization conditions of the composition, which may include elevated temperatures, freeze-thaw cycles, changes in pH or in ionic strength, UV-irradiation, presence of harmful chemicals and the like.According to specific embodiments, the integrity and activity of the composition is maintained under storage and / or utilization conditions of the composition, which may include elevated temperatures, freeze-thaw cycles, changes in pH or in ionic strength, UV-irradiation, presence of harmful chemicals and the like.According to specific embodiments, the integrity and activity of the composition is maintained under open field or controlled conditions, e.g., greenhouse.It should be noted that the compositions disclosed herein can be formulated with various carriers designed to increase e.g. delivery, stability, permeability and the like.A "carrier", as used herein, means any solid, semi-solid or liquid carrier in or on(to) which a compound (e.g. nanobody and / or toxin, composition comprising same) can be suitably incorporated, included, immobilized, adsorbed, absorbed, bound, encapsulated, embedded, attached, or comprised. Non-limiting examples of such carriers include nanocapsules, microcapsules, nanospheres, microspheres, nanoparticles, microparticles, liposomes, vesicles, beads, a gel, weak ionic resin particles, liposomes, cochleate delivery vehicles, small granules, granulates, nano-tubes, bucky-balls, water droplets that are part of an water-in-oil emulsion, oil droplets that are part of an oil-in-water emulsion, organic materials such as cork, wood or other plant-derived materials (e.g. in the form of seed shells, wood chips, pulp, spheres, beads, sheets or any other suitable form), paper or cardboard, inorganic materials such as talc, clay, microcrystalline cellulose, silica, alumina, silicates and zeolites, or even microbial cells (such as yeast cells) or suitable fractions or fragments thereof.According to specific embodiments, the carriers are such that they have immediate or gradual or slow-release characteristics, for example over several minutes, several hours, several days or several weeks. Also, the carriers may be made of materials (e.g. polymers) that rupture or slowly degrade (for example, due to prolonged exposure to high or low temperature, sunlight, highor low humidity or other environmental factors or conditions) over time (e.g. over minutes, hours, days or weeks) and so release the compound (e.g. nanobody and / or toxin, composition comprising same) from the carrier. According to specific embodiments, the carrier is coupled, bound, linked or otherwise attached to or associated with the compound. According to specific embodiments, the carrier is covalently coupled to the compound.The compositions disclosed herein (e.g. the nanobodies, the composition comprising the nanobody and the toxin, polynucleotides and nucleic acid constructs encoding same and host cells expressing same) may be formulated in a composition such as an agrochemical or insecticidal composition where is mixed with suitable physiologically acceptable carriers or excipients.Herein the term "active ingredient" refers to the nanobodies, the composition comprising the nanobody and the toxin, thepolynucleotides and nucleic acid constructs encoding same and the host cells expressing same accountable for the biological effect.An "agrochemical formulation" as used herein means a composition for agricultural use, comprising one or more of the active ingredients described with other chemical components such as agriculturally acceptable carriers and excipients.Hereinafter, the phrase "physiologically acceptable carrier" refers to a carrier or a diluent that does not cause significant irritation to an organism and does not abrogate the biological activity and properties of the administered compound. An adjuvant is included under these phrases.According to specific embodiments, the composition is formulated with an agriculturally acceptable carrier. Suitable agricultural carriers can be solid or liquid and are well known in the art. The term "agriculturally acceptable carrier" covers all adjuvants, e.g., inert components, dispersants, surfactants, tackifiers, binders, etc. that are ordinarily used in insecticide formulation technology and are well known to the skilled artisan.Herein the term "excipient" refers to an inert substance added to a composition to further facilitate administration of an active ingredient. Examples, without limitation, of excipients include calcium carbonate, calcium phosphate, various sugars and types of starch, cellulose derivatives, surfactant, gelatin, vegetable oils, polyethylene glycols, wetting agents, spreading agents, buffering agents, acidifiers and the like.According to specific embodiments, the compositions disclosed herein (e.g. the nanobodies, the composition comprising the nanobody and the toxin, polynucleotides and nucleic acid constructs encoding same and host cells expressing same) may be the only active substance in the composition.According to other specific embodiments, the composition comprises one or more additional active agents in addition to the compositions disclosed herein (e.g. the nanobodies, thecomposition comprising the nanobody and the toxin, polynucleotides and nucleic acid constructs encoding it and host cells expressing it). Non-limiting examples of such agents include herbicides, insecticides, plant growth regulators, insecticidal nanobodies, safeners and the like.According to specific embodiments, the composition disclosed herein and the additional active agent are in a co-formulation.According to specific embodiments, the composition disclosed herein and the additional active agent are in separate containers.According to other specific embodiments, the composition may comprise an insect attractant. The attractant may be a pheromone, such as a male or female pheromone for example. As an example, the pheromones referred to in the book "Insect Pheromones and their use in Pest Management" (Howse et al, Chapman and Hall, 1998) may be used in the invention.The attractant may be present in the formulation or it may be applied separately from the formulation, to ensure that the insects are attracted to the site where the formulation is applied.The nanobody and the compositions comprising the nanobody and the toxin of some embodiments of the invention are endowed with an insect control activity.As used herein, the term “insect control” refers to preventing, inhibiting or reducing the ability of an insect to feed, grow, move, spread, develop, survive, and / or reproduce, and / or to limit insect-related damage, which may be manifested by e.g. killing of the insect, decreasing insect survival or longevity, decreasing insect's fecundity and / or fertility, decreasing or arresting insect's feeding, decreasing or arresting insect's growth, decreasing or arresting insect's development, decreasing or arresting insect’ s mobility and / or preventing infestation by an insect.According to specific embodiments, the insect control activity is manifested by killing of the insect.Methods of determining insect control activity are well known to the skilled in the art and are also disclosed in the Examples section which follows and include, but are not limited to in-vitro growing an insect in the presence of the nanobody or the composition comprising same and determining mortality, development, weight, length, mobility etc., as compared to same in the absence of the nanobody or the composition.According to specific embodiments, the insect control activity is manifested by increased mortality of the insect in the presence of the nanobody in comparison to its mortality in the absence of the nanobody.According to specific embodiments, the increased mortality is statistically significant.According to specific embodiments, the increased mortality is of at least 5 %, at least 10 %, at least 20 %, at least 30 %, at least 40 %, at least 50 %, at least 60 %, at least 70 %, at least 80%, at least 90 %, at least 95 %, at least 100 %, at least 2 fold, at least 5 fold, at least 10 fold, or at least 100 fold as compared to same in the absence of the nanobody.The nanobody disclosed herein may have an insect control activity by itself or it may exert its insect control activity by delivering a toxin to an insect.Thus, according to specific embodiments, binding of the nanobody to the insect CDA confers an insect control activity to the nanobody.According to specific embodiments, the nanobody downregulates activity of the insect CDA.As used herein, “downregulates activity” refers to a decrease of at least 5 % in biological function of the insect polypeptide (i.e. CDA) in the presence of the nanobody in comparison to its biological function in the absence of the nanobody, as determined by a method suitable for determining activity of the insect polypeptide. As the CDA comprises both a chitin binding domain (e.g. amino acid residues C25 to C82 of SEQ ID NO: 1) and a catalytic domain (e.g. amino acid residues S345 to P453 of SEQ ID NO: 1), the nanobody of some embodiments of the invention may bind and downregulate activity of the binding domain and / or the catalytic domain. Thus, for example determining the activity of CDA may be effected by e.g. ELISA, Western blot analysis, immunoprecipitation, flow cytometry, a colorimetric or fluorometric ATPase assay, or a chaperone activity assay.According to other specific embodiments the decrease is by at least 10 %, at least 20 %, at least 30 %, at least 40 %, at least 50 %, at least 60 %, at least 70 %, at least 80 %, at least 90 %, at least 95 %, at least 99 % or 100 % as compared to same in the absence of the nanobody, as may be determined by e.g. any of the methods described hereinabove.According to additional or alternative embodiments, the nanobody is a targeting agent, which serves to provide specific delivery of e.g. a toxin having an insect control activity to the insect.Non-limiting examples of toxins and methods of coupling them to the nanobody are further described hereinabove.As the nanobodies and compositions comprising the nanobody and the toxin of some embodiments of the invention are endowed with insect control activity, the present invention also encompasses methods of insect control.Thus, according to an aspect of the present invention there is provided a method of insect control, the method comprising contacting the insect with the nanobody or the composition comprising the nanobody and the toxin, a polynucleotide or a nucleic acid construct encoding same or a host cell expressing same.According to specific embodiments, the contacting comprises applying the nanobody or the composition comprising the nanobody and the toxin directly to the insect.According to specific embodiments, the contacting comprises applying the nanobody or the composition comprising the nanobody and the toxin to an organism or a surface, which may be in contact with said insect.According to another aspect of the present invention, there is provided a method of preventing insect infestation of a commodity product, the method comprising adding to the product the nanobody or the composition comprising the nanobody and the toxin.According to another aspect of the present invention, there is provided a method of preventing insect infestation of a commodity product, the method comprising packaging the product in a packaging material comprising the nanobody or the composition comprising the nanobody and the toxin.The contacting or the adding may be effected using any suitable method known in the art, including, but not limited to spraying (including high volume (HV), low volume (LV) and ultra low volume (ULV) spraying), atomizing, brushing, dressing, dripping, coating, dipping, immersing, submerging, encrusting, spreading, foaming, fogging, injecting, adding to a culture, irrigating, applying as small droplets, a mist or an aerosol, recombinantly expressing the nucleic acid construct in a cell of an organism (as further disclosed hereinabove).According to specific embodiments, contacting or adding is effected by spraying, irrigating and / or fumigation.According to specific embodiments, contacting or adding is effected by introducing the polynucleotide or the nucleic acid construct into a cell of the organism.According to specific embodiments, the organism is a plant.As used herein, the term “surface” refers to any object, which may be in contact with an insect. Non-limiting surfaces include nets (e.g. mosquito nets), a light source, a colored object, a shape or silhouette that stand out of a contrasting background greenhouse, outdoor camping facilities, soil and the like.According to specific embodiments, the commodity product is produced from a plant.The term '"plant" as used herein encompasses whole plants, a grafted plant, ancestors and progeny of the plants and plant parts, including seeds, shoots, stems, roots (including tubers), rootstock, scion, fruits, vegetables, flowers and plant cells, tissues and organs. The plant may be in any form including suspension cultures, embryos, meristematic regions, callus tissue, leaves, gametophytes, sporophytes, pollen, and microspores.According to specific embodiments, the plant is a crop. “Crop” as used herein means a plant species or variety that is grown to be harvested as food, livestock fodder, fuel raw material, or for any other economic purpose. As a non-limiting example, the crops can be maize, cereals, such as wheat, rye, barley and oats, sorghum, rice, sugar beet and fodder beet, fruit, such as pome fruit (e.g., apples and pears), citrus fruit (e.g., oranges, lemons, limes, grapefruit, or mandarins), stone fruit (e.g., peaches, nectarines or plums), nuts (e.g., almonds or walnuts), soft fruit (e.g., cherries, strawberries, blackberries or raspberries), the plantain family or grapevines, leguminous crops, such as beans, lentils, peas and soya, oil crops, such as sunflower, safflower, rapeseed, canola, castor or olives, cucurbits, such as cucumbers, melons or pumpkins, fiber plants, such as cotton, flax or hemp, fuel crops, such as sugarcane, miscanthus or switchgrass, vegetables, such as potatoes, tomatoes, peppers, lettuce, spinach, onions, carrots, eggplants, asparagus or cabbage, ornamentals, such as flowers (e.g., petunias, pelargoniums, roses, tulips, lilies, or chrysanthemums), herbs (e.g. basil, mentha), shrubs, broad-leaved trees (e.g., poplars or willows) and evergreens (e.g., conifers), grasses, such as lawn, turf or forage grass or other useful plants, such as coffee, tea, tobacco, hops, pepper, medical plants (e.g. Cannabis), rubber or latex plants.According to specific embodiments, the plant may be selected from the group consisting of maize, soybean, alfalfa, cotton, sunflower, Brassica oil seeds such as Brassica napus (e.g. canola, rape- seed), Brassica rapa, Brassica juncea (e.g. (field) mustard) and Brassica carinata, Arecaceae sp. (e.g. oilpalm, coconut), rice, wheat, sugar beet, sugar cane, oats, rye, barley, millet and sorghum, triticale, flax, nuts, grapes and vine and various fruit and vegetables from various botanic taxa, e.g. Rosaceae sp. (e.g. pome fruits such as apples and pears, but also stone fruits such as apricots, cherries, almonds, plums and peaches, and berry fruits such as strawberries, raspberries, red and black currant and gooseberry), Ribesioidae sp., Juglandaceae sp., Betulaceae sp., Anacardiaceae sp., Fagaceae sp., Moraceae sp., Oleaceae sp. (e.g. olive tree), Actinidaceae sp., Lauraceae sp. (e.g. avocado, cinnamon, camphor), Musaceae sp. (e.g. banana trees and plantations), Rubiaceae sp. (e.g. coffee), Theaceae sp. (e.g. tea), Sterculiceae sp., Rutaceae sp. (e.g. lemons, oranges, mandarins and grapefruit); Solanaceae sp. (e.g. tomatoes, potatoes, peppers, capsicum, aubergines, tobacco), Liliaceae sp., Compositae sp. (e.g. lettuce, artichokes and chicory - including root chicory, endive or common chicory), Umbelliferae sp. (e.g. carrots, parsley, celery and celeriac), Cucurbitaceae sp. (e.g. cucumbers - including gherkins, pumpkins, watermelons, calabashes and melons), Alliaceae sp. (e.g. leeks and onions), Cruciferae sp. (e.g. white cabbage, red cabbage, broccoli, cauliflower, Brussels sprouts, pak choi, kohlrabi, radishes, horseradish, cress and Chinese cabbage), Leguminosae sp. (e.g. peanuts, peas, lentils and beans - e.g. common beans and broad beans), Chenopodiaceae sp. (e.g. Swiss chard, fodder beet, spinach, beetroot), Linaceae sp. (e.g.hemp), Cannabeacea sp. (e.g. cannabis), Malvaceae sp. (e.g. okra, cocoa), Papaveraceae (e.g. poppy), Asparagaceae (e.g. asparagus); useful plants and ornamental plants in the garden and woods including turf, lawn, grass and Stevia rebaudiana, and genetically modified types of these plants.According to specific embodiments, the plant may be a harvestable part of the plant selected from the group consisting of a fruit, a flower, a nut, a vegetable, a fruit or vegetable with inedible peel, such as avocados, bananas, plantains, lemons, grapefruits, melons, oranges, pineapples, kiwi fruits, guavas, mandarins, mangoes and pumpkin.According to specific embodiments, the plant is forest plant, such as described in e.g. www(dot)fao(dot)org / 3 / i0640e / i0640el3(dot)pdf.According to specific embodiments, the plant is an ornamental plant.According to specific embodiments, the plant may be a cut flower of ornamental plants, preferably selected from Alstroemeria, carnation, Chrysanthemum, Freesia, Gerbera, Gladiolus, baby's breath (Gypsophila spp.), Helianthus, Hydrangea, Lilium, Lisianthus, roses and summer flowers.According to specific embodiments, the plant is a cut grass or wood.According to specific embodiments, the plant is cotton.According to specific embodiments, the plant is a transgenic plant.According to specific embodiments, the plant is a transgenic plant recombinantly expressing the nanobody or the composition comprising the nanobody and the toxin.Methods of generating a transgenic plant are well known in the art and are also described hereinabove.Following, the present invention also encompasses products comprising the nanobody or the composition comprising the nanobody and the toxin, polynucleotides or nucleic acid constructs encoding same or host cells expressing same.According to specific embodiments, such products are more resistant to insect infestation or damage as compared to products not comprising the nanobody or the composition comprising the nanobody and the toxin, polynucleotides or nucleic acid constructs encoding same or host cells expressing same.Thus, according to an aspect of the present invention, there is provided a plant comprising the nanobody or the composition comprising the nanobody and the toxin, or a polynucleotide or a nucleic acid construct encoding same.According to an additional or an alternative aspect of the present invention, there is provided a commodity product comprising the nanobody or the composition comprising the nanobody and the toxin.According to an additional or an alternative aspect of the present invention, there is provided a surface covered with the nanobody or the composition comprising the nanobody and the toxin.According to an additional or an alternative aspect of the present invention, there is provided a packaged product comprising a commodity product contained within a packaging material comprising the nanobody or the composition comprising the nanobody and the toxin. Tables 1-2 hereinbelow list CDA polypeptides and nanobodies that can be used with specific embodiments of the present invention.Table 1: Target Spodopterafrugiperda chitin deacetylase (CDA) Amino Acid SequenceTable 2: Amino acid sequences of anti-CDA NanobodiesTable 3: Epitope mapping indicating in bold the amino acid residues in Spodopterafrugiperda CDA (SEQ ID NO: 1) which interact with anti-CDA nanobodiesTable 4: Amino acid sequence of CDA of different insects, indicating in underline the catalytic domain and in bold the amino acid residues corresponding to the amino acid residues of Spodoptera frugiperda CDA (SEQ ID NO: 1) which interact with the anti-CDA nanobody CDA-SF-1DTable 5: Amino acid sequence of CDA of different insects, indicating in underline the chitin binding and catalytic domains and in bold the amino acid residues corresponding to the amino acid residues of Spodoptera frugiperda CDA (SEQ ID NO: 1) which interact with the anti-CDA nanobody CDA-SF-2CAs used herein the term “about” refers to ± 10 %The terms "comprises", "comprising", "includes", "including", “having” and their conjugates mean "including but not limited to". The term “consisting of’ means “including and limited to”.The term "consisting essentially of" means that the composition, method or structure may include additional ingredients, steps and / or parts, but only if the additional ingredients, steps and / orparts do not materially alter the basic and novel characteristics of the claimed composition, method or structure.As used herein, the singular form "a", "an" and "the" include plural references unless the context clearly dictates otherwise. For example, the term "a compound" or "at least one compound" may include a plurality of compounds, including mixtures thereof.Throughout this application, various embodiments of this invention may be presented in a range format. It should be understood that the description in range format is merely for convenience and brevity and should not be construed as an inflexible limitation on the scope of the invention. Accordingly, the description of a range should be considered to have specifically disclosed all the possible subranges as well as individual numerical values within that range. For example, description of a range such as from 1 to 6 should be considered to have specifically disclosed subranges such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6 etc., as well as individual numbers within that range, for example, 1, 2, 3, 4, 5, and 6. This applies regardless of the breadth of the range.Whenever a numerical range is indicated herein, it is meant to include any cited numeral (fractional or integral) within the indicated range. The phrases “ranging / ranges between” a first indicate number and a second indicate number and “ranging / ranges from” a first, indicate number “to” a second indicate number are used herein interchangeably and are meant to include the first and second indicated numbers and all the fractional and integral numerals therebetween.As used herein the term "method" refers to manners, means, techniques and procedures for accomplishing a given task including, but not limited to, those manners, means, techniques and procedures either known to, or readily developed from known manners, means, techniques and procedures by practitioners of the chemical, pharmacological, biological, biochemical and medical arts.When reference is made to particular sequence listings, such reference is to be understood to also encompass sequences that substantially correspond to its complementary sequence as including minor sequence variations, resulting from, e.g., sequencing errors, cloning errors, or other alterations resulting in base substitution, base deletion or base addition, provided that the frequency of such variations is less than 1 in 50 nucleotides, alternatively, less than 1 in 100 nucleotides, alternatively, less than 1 in 200 nucleotides, alternatively, less than 1 in 500 nucleotides, alternatively, less than 1 in 1000 nucleotides, alternatively, less than 1 in 5,000 nucleotides, alternatively, less than 1 in 10,000 nucleotides.It is appreciated that certain features of the invention, which are, for clarity, described in the context of separate embodiments, may also be provided in combination in a single embodiment.Conversely, various features of the invention, which are, for brevity, described in the context of a single embodiment, may also be provided separately or in any suitable subcombination or as suitable in any other described embodiment of the invention. Certain features described in the context of various embodiments are not to be considered essential features of those embodiments, unless the embodiment is inoperative without those elements.Various embodiments and aspects of the present invention as delineated hereinabove and as claimed in the claims section below find experimental support in the following examples.EXAMPLESReference is now made to the following examples, which together with the above descriptions illustrate some embodiments of the invention in a non-limiting fashion. Generally, the nomenclature used herein and the laboratory procedures utilized in the present invention include molecular, biochemical, microbiological and recombinant DNA techniques.MATERIALS AND METHODSProtein target preparation for immunization - A DNA sequence encoding the target CDA of Spodoptera frugiperda (see Table 1 hereinabove) was optimized and synthesized. The synthesized sequence was cloned with His tag into apET-28a or pET-30a vector and expressed in E. coli. strain BL21 Star (DE3). A single colony was inoculated into LB medium containing kanamycin; and the culture was incubated at 37 °C at 200 rpm and then induced with Isopropyl p- D- 1- thiogalactopyranoside (IPTG). SDS-PAGE analysis was used to monitor protein expression. Following, BL21 Star (DE3) stored in glycerol was inoculated into TB medium containing kanamycin and cultured at 37 °C. When the OD600 reached 1.2, cell culture was induced with IPTG at 15 °C for 16 hours. Cells were harvested by centrifugation and pellets were resuspended with lysis buffer (20 mM NaPi pH7.4, 500 mM NaCl, 20 mM Imidazole, Protease Inhibitor cocktail - cOmplete™, EDTA-free Protease Inhibitor Cocktail - Roche cat#4693132001) followed by sonication and centrifugation. The precipitate was dissolved using urea; and the denatured supernatant was kept for future purification. Following, the protein was purified from the supernatant using a Ni-NTA column (GE-Healthcare, Cat No. 17-5318-02): The column was washed with 10 bed volumes of wash buffer (20 mM NaPi pH7.4, 500 mM NaCl, 50 mM Imidazole) and the protein was eluted with elution buffer (20 mM NaPi pH7.4, 500 mM NaCl, 500 mM Imidazole). Following the elution, the fractions were placed in MEGA tubes with membrane cutoff of 3.5 kDa (Tivan Biotech MEGA3-50) and dialyzed in IL PBS pH7.4 at 4 °Covernight, followed by a second round of dialysis under the same conditions. The protein purity and molecular weight were determined by a standard SDS-PAGE.Immunization - A llama was subcutaneously injected on days 0, 7, 14, 21, 28 and 35, each time with about 125 or 150 pg target protein in combination with a Gerbu adjuvant P (Gerbu Biotech, #3111-0025). On day 40, about 100 ml anti-coagulated blood was collected from the llama for lymphocyte preparation.Construction of a VHH library - A VHH library was constructed from the llama lymphocytes to screen for the presence of antigen- specific nanobodies. To this end, total RNA from peripheral blood lymphocytes was used as a template for first strand cDNA synthesis with an oligo(dT) primer. Using this cDNA, the VHH encoding sequences were amplified by PCR, digested with PstI (#ER0611 from Thermofischer) and Notl (#11037668001 from Sigma), and cloned into the PstI & Notl sites of the phagemid vector pMECS . The VHH library comprised about 108independent transformants, with about 80-92 % of transformants harboring the vector with the right insert size.Isolation and sequencing of specific target nanobodies ■ The library was panned for 3 rounds on solid-phase coated with the target antigen (100 pg / ml in 100 mM NaHCO3 pH 8.2). The enrichment for antigen- specific phages was assessed following each round of panning by comparing the number of phagemid particles eluted from antigen-coated wells with the number of phagemid particles eluted from negative control (uncoated blocked) wells. These experiments indicated that the phage population was enriched for antigen-specific phages by the 3rd round. The antigen used for panning and ELISA screening was the same as the one used for immunization, using uncoated blocked wells as a negative control. The amino acid sequences of the generated nanobodies are shown in Table 2 hereinabove.Nanobodies expression and purification ■ The nanobodies DNA sequence were optimized and synthesized by GenScript (provided in SEQ ID Nos: 429-468). The synthesized sequences were cloned with His tag into a pET-28b+ vector for protein expression in E. coli. Following, E. coli SHuffle T7 express were transformed with the recombinant plasmids. A single colony was inoculated into TB medium containing kanamycin; and the culture was incubated at 30 °C at 200 rpm overnight. Following, SHuffle T7 express starter was inoculated into larger volume of TB medium containing kanamycin and cultured at 30 °C at 200 rpm. When the OD600 reached 0.6- 0.8, cell culture was induced with 0.7 mM IPTG at 30 °C for 20-22 hours. Cells were harvested by centrifugation and cell pellets were resuspended with lysis buffer (20 mM NaPi pH7.5, 500 mM NaCl, 20 mM imidazole) followed by sonication and centrifugation. The supernatant was kept for purification. The nanobodies were purified with a Ni-Sepharose column. The column waswashed with 5 bed volumes of Wash Buffer (20mM NaPi pH7.5, 500mM NaCl, 50mM imidazole) and the protein was eluted with elution buffer (20 mM NaPi pH7.5, 500 mM NaCl, 500 mM imidazole). Following, elution fractions were desalted with columns contains Sepharose G-25 beads and PBS elution buffer (pH 7.4). The relevant fractions were collected, and concentration was determined by Nanodrop. Protein purity and molecular weight were determined by standard SDS-PAGE followed by Coomassie stain.Insect culture - Spodoptera frugiperda colonies were collected from cotton fields in Israel and reared in the laboratory at 24 °C with 65 % relative humidity on a 10 hours day / 14 hours night photoperiod. The collected larvae were kept on an artificial diet with Ward’s diet powder Stonefly Heliothis Diet (Product No. 38-0600, Ward’s Natural Science, Rochester, NY) supplemented with Vitamin mixture (Nicotinic acid 40 pM, Calcium pantothenate 5 pM, Riboflavin 5 pM, Thiamine hydrochloride 4 pM, Pyridoxine hydrochloride 5 pM, Folic acid 2.5 pM, D-biotin 4 pM and Cyanocobalamin 5 nM), Sorbic acid 0.2 %, Methylparaben 0.4 %, Ascorbic acid 0.25 %, Brewer Yeast 1 %, white vinegar 4 % and Linseed oil 0.5 %. Bemisia tabaci and Myzus persicae colonies were collected outdoors and maintained separately in growth chambers at 22 ± 3 °C under continuous lighting. The Bemisia tabaci were grown on cotton plants and Myzus persicae on pepper plants. The whitefly colony of Bemisia tabaci that was used in this study was a mix of B and Q biotypes using the procedure described by De Barro et al. (2003) Molecular Ecology Notes, 3(1), 40-43.Cotton leaf disc bioassay for Spodoptera frugiperda - 1 mL of sterilized co-agar was added into each well of 12 wells plates. After the agar cooled down a cotton disc leaf with a diameter of 2.0 cm was deposited it in each well and then overlaid with 50 pl suspension of the tested nanobody in a concentration of 2 to 4 mg I ml or PBS control. One 24-48 hours old larva was added to each well, the plates were coated with polyofin sealing foil (HJ-BIOANALITIC, Cat No. 900371) and incubated in the laboratory at 24 °C with 70 % relative humidity in the dark. Following 4 days of incubation, the larvae were moved to a 12 wells dish with a cotton disc leaf having a diameter of 2.0 cm with 50 pl of the tested nanobody. Larvae mortality was measured following 4 and 7 days of incubation. Each study was included 12 replicates of each treatment and each study was performed three times.Liquid bioassay for Bemisia tabaci and Myzus persicae - The test was performed using liquid diet-containing sachets / envelopes made of stretched parafilm (“Parafilm M”) membranes. These are made by hand and filled manually using a pipette, with approximately 100 pl of the spiked diet per sachet. The artificial liquid diet comprises IPL41 ( l) insect medium culture (Gibco, CAS 11405-081) supplemented with 30 % sucrose and 0.5 % arginine diluted, the artificialliquid diet was deluted 1 to 1 with nanobody stock solution containing 1 mg / ml in PBS or PBS for control. For dose-range tests the nanobody stock was diluted to the required degree by mixing with PBS prior to incorporation into the liquid diet. The sachet is then sealed to prevent leakage of the test material and is placed in a perspex tube (approx. 22 mm outside diameter x 22 mm height) together with a test population of 10 none winged nymph stage aphids. The open ends of the tubes are closed with a parafilm seal.Pepper plant bioassay for Myzus persicae ( nanobody applied prior to aphid introduction ) - Pepper plants grown under climatic conditions of 25 °C mean daily, 57 % humidity and natural light, served as hosts. When plants reached six to eight weeks old, they were sprayed with 0.6 to 1.4 ml of the tested nanobody in a concentration of 1 to 4 mg / ml or with PBS as control. Spayed plants were transferred into a plastic Insect Cage (BugDorm-6E610). To each plant, 20 aphids nymph stages N2-N3 were added followed by incubation in the laboratory at 24 °C. Aphid mortality was measured after 24, 48 and 72 hours of incubation. Each study was done with 4 replicates of each treatment.Pepper green-house plant bioassay for Myzus persicae (nanobody applied post aphid introduction ) - Pepper plants were cultivated under climate-controlled conditions at a mean daily temperature of 25 °C and 57 % humidity, with natural light exposure. When plants reached an age of six to eight weeks, 20 aphids nymph stages N2-N3 were introduced to each plant. Following a one-day acclimation period, plants were sprayed with 0.8 ml of the tested nanobody solution at a final concentration of 1 mg / ml or 3 mg / ml, or with water as a negative control. The plants were then transferred into plastic Insect Cages (BugDorm-6E610) and incubated in the climate-controlled greenhouse. Myzus persicae mortality was measured on days 1 and 5 postspraying. Each study was conducted 3 times, with 3-10 independent replicates of each treatment.Pepper green-house plant bioassay for Bemisia tabaci (nanobody applied post aphid introduction ) - Pepper plants were cultivated under climate-controlled conditions at a mean daily temperature of 25 °C and 57 % humidity, with natural light exposure. When plants reached six to eight weeks of age, they were transferred into plastic Insect Cages (BugDorm-6E610). Each plant was then inoculated with 100 adult aphids; and following a one-day acclimation period, sprayed twice on days 0 and 6 with 0.8 ml of the tested nanobody solution at a final concentration of 1 mg / ml or 3 mg / ml, or with water as a negative control. Bemisia tabaci mortality was measured on days 1, 5, 7, and 12 post-spraying. Each study was conducted twice, with four independent replicates of each treatment.Cotton green-house plant bioassay for Spodoptera frugiperda (nanobody applied post larvae introduction) - Cotton plants were cultivated under climate-controlled conditions at a meandaily temperature of 25 °C and 57 % humidity, with natural light exposure. When plants reached an age of six to eight weeks, 16 Larvae L2 stage (72 hours after hatching), were introduced to each plant. Following a one-day acclimation period, plants were sprayed with 1.5 ml of the tested nanobody solution at s final concentrations of 1 mg / ml or 3 mg / ml, or with water as a negative control. The plants were then transferred into plastic Insect Cages (BugDorm-6E610) and incubated in the climate-controlled greenhouse. Spodoptera frugiperda mortality was measured on days 1 and 5 post-spraying. Each study was conducted 4 times, with 3-10 independent replicates of each treatment.Epitope mapping - The interaction between the target CDA (SEQ ID NO: 1) and the nanobody was analyzed using computational modeling tools for identification of specific amino acids involved in their binding. Briefly, the nanobody’s 3D structure and target CDA sequence were computed using homology modeling based on known proteins structures. In the next step, an initial binding pose for the protein-nanobody pair was predicted via a Alphafold 2 Multimer model. Following, the nanobody homology model was aligned into the expected pose from AF2 and the combined structure was refined using Rosetta Snugdock and Rosetta relax. Finally, all selected best models were combined and passed through quality assurance by MolProbity and manual inspection. The result was a high-resolution 3D structure of the target CDA sequence and the nanobody pair and identification interaction and relations of their amino acids.EXAMPLE 1INSECTICIDAL EFFECT OF ANTI-CDA NANOBODIESSeveral nanobodies were generated against the Spodoptera frugiperda CDA (see Tables 1- 2 hereinabove). The insecticidal activity of the generated nanobodies was evaluated in three different bioassays, namely a Cotton leaf disc bioassay, a liquid bioassay, and a Pepper plant bioassay (in which the nanobodies were applied prior to insect introduction), using three different insects, Spodoptera frugiperda, Bemisia tabaci and Myzus persicae respectively.As shown in Figures 1-6, the anti-CDA nanobodies CDA-SF-1D (SEQ ID NO: 14), CDA- SF-2C (SEQ ID NO: 82), and CDA-SF-3B (SEQ ID NO: 94) induced significant mortality in all assays performed. While the observed effect was clearly dose-dependent, mortality above 80 % appeared already at a dose of 1 mg / ml.EXAMPLE 2EPITOPE MAPPING OF THE ANTI-CDA NANOBODY CDA-SF-1DIdentification of the amino acids in CDA of Spodoptera frugiperda (SEQ ID NO: 1) which interact with the anti CDA nanobody CDA-SF ID (SEQ ID NO: 14) was performed by computational modeling tools, as detailed hereinabove. This analysis indicated that nanobody CDA-SF-1D interacts with amino acids: ASP(D)170, ASP(D)175, GLU(E)360, ASP(D)361, ASP(D)365, ASP(D)384, TYR(Y)387, ASN(N)388, ASN(N)391, HIS(H)392, ASP(D)395, TYR(Y)398, GLU(E)399, GLU(E)419, GLU(E)422, GLU(E)430, SER(S)433 and SER(S)434, see Table 3 hereinabove. More specifically, the CRD3 region of CDA-SF-1D binds to the following 7 amino acids: GLU(E)360, ASP(D)361, ASP(D)365, ASP(D)384, HIS(H)392, GLU(E)419 and GLU(E)422.Chitin deacetylases (CDAs, EC No. 3.5.1.41) are secreted metalloproteins belonging to a family of extracellular chitin-modifying enzymes that catalyze the N-deacetylation of chitin, a beta-l,4-linked N-acetylglucosamine polymer, to form chitosan, a polymer of beta-(l,4)-linked d- glucosamine residues. CDAs have been isolated and characterized by various insect, bacterial and fungal species and belong to the larger carbohydrate esterase 4 (CE4) superfamily. Analysis of the CDA sequence in NCBI in combination with BLAST showed that amino acid residues SER(S)345 to PRO(P)453 comprise the catalytic site of CE4_CDA_like_l , identified as a putative catalytic domain of chitin deacetylase-like proteins with additional chitin-binding peritrophin-A domain (ChBD) and / or a low-density lipoprotein receptor class A domain (LDLa). As CDA-SF- 1D binds to 16 amino acids in this catalytic region it can be assumed that it blockes the catalytic region of the enzyme.EXAMPLE 3EPITOPE MAPPING OF THE ANTI-CDA NANOBODY CDA-SF-2CIdentification of the amino acids in CDA of Spodoptera frugiperda (SEQ ID NO: 1) which interact with the anti CDA nanobody CDA-SF-2C (SEQ ID NO: 82) was performed by computational modeling tools, as detailed hereinabove. This analysis indicated that nanobody CDA-SF-2C interacts with amino acids: VAL(V)22, GLU(E)23, LEU(L)24, CYS(C)25, ASP(D)46, HE(I)48, IIE(I)68, GLU(E)99, PRO(P)100, LEU(L)101, CYS(C)102, ARG(R)286, AAL(A)287, GLY(G)293, GLY(G)294, ASN(N)295, ASN(N)296, GLN(Q)297, MET(M)301, GLU(E)302, GLU(E)303, GLN(Q)304, LEU(L)307, TYR(Y)3O8, ASP(D)309, SER(S)310, THR(T)311, IIE(I)312, PRO(P)319, PRO(P)320, PRO(P)323, TYR(Y) 324, TYR (T)325, TYR(Y)327, PHE(F)328, HIS(H)332, ARG(R)333, CYS(C)334, HIS(H)335, GLY(G)336,ASN(N)337, LEU(L)338, GLN(Q)339, SER(S)340, CYS(C)341, PRO(P)342, THR(T)343, ARG(R)344, TRP(W)349, GLU(E)350, MET(M)351, VAL(V)352, ASN(N)354, GLU(E)355, ASP(D)357, ARG(R)358, GLU(E)360, PRO(P)362, ASN(N)364, GLU(E)366, MET(M)373, VAL(V)374, ASP(D)375, ASN(N)391, HIS(H)392, ASP(D)395, TYR(Y)398, GLU(E)399, AAL(A)403, PRO(P)404, LEU(L)405, GLY(G)406, ARG(R)415, SER(S)434, MET(M)443, TYR(T)444, GLN(Q)445, VAL(V)446, IIE(I)447, GLN(Q)448, PRO(P)475, CYS(C)477, TRP(W)478, VAL(V)479, PRO(P)480, SER(S)482, CYS(C)483, LYS(K)484, LEU(L)485, TYR(T)499, CYS(C)500, VAL(V)501, ARG(R)502, PRO(P)508, LEU(L)510, ASN(N)511, ASP(D)512, ASP(D)516, GLY(G)517, HIS(H)518 and TYR(Y)519, see Table 3 hereinabove. More specifically, the CRD3 region of CDA-SF-2C binds with the following 3 amino acids: GLU(E)350, MET(M)351 & VAL(V)352.Analysis of the CDA sequence in NCBI in combination with BLAST showed that amino acid residues CYS(C)25 to CYS(C)82 comprise the CBM_14 Chitin binding Peritrophin-A domain called the Peritrophin-A domain, found in chitin binding proteins particularly peritrophic matrix proteins of insects and amino acid residues SER(S)345 to PRO(P)453 comprise the catalytic site of CE4_CDA_like_l, identified as a putative catalytic domain of chitin deacetylase- like proteins with additional chitin-binding peritrophin-A domain (ChBD) and / or a low-density lipoprotein receptor class A domain (LDLa). As CDA-SF-2C binds to 4 amino acids in the chitin binding site reigon and to 32 amino acids in the catalytic region, it can be assumed that it blocks the chitin binding site and / ot the catalytic region of the enzyme.EXAMPLE 4INSECTICIDAL EFFECT OF ANTI-CDA NANOBODIESThe insecticidal activity of the anti-CDA nanobody CDA-SF-2C (SEQ ID NO: 82) was evaluated in a pepper and cotton green-house plant bioassays (in which the nanobodies were applied post insect introduction), using three different insects, Myzus persicae, Bemisia tabaci and Spodopterafrugiperda.As shown in Figures 7-9, the anti-CDA nanobody CDA-SF-2C (SEQ ID NO: 82) induced significant mortality in all assays performed. While the observed effect was clearly dosedependent, mortality appeared already at a dose of 1 mg I ml.Although the invention has been described in conjunction with specific embodiments thereof, it is evident that many alternatives, modifications and variations will be apparent to those skilled in the art. Accordingly, it is intended to embrace all such alternatives, modifications and variations that fall within the spirit and broad scope of the appended claims.It is the intent of the applicant(s) that all publications, patents and patent applications referred to in this specification are to be incorporated in their entirety by reference into the specification, as if each individual publication, patent or patent application was specifically and individually noted when referenced that it is to be incorporated herein by reference. In addition, citation or identification of any reference in this application shall not be construed as an admission that such reference is available as prior art to the present invention. To the extent that section headings are used, they should not be construed as necessarily limiting. In addition, any priority document(s) of this application is / are hereby incorporated herein by reference in its / their entirety.

Claims

WHAT IS CLAIMED IS:

1. A nanobody which specifically binds to a non-linear epitope of insect CDA, said non-linear epitope is in the catalytic and / or chitin binding domain of said insect CDA, wherein binding of said nanobody to said insect CDA confers an insect control activity to said nanobody.

2. A nanobody which specifically binds to a non-linear epitope of insect CDA, said non-linear epitope comprises an amino acid residue selected from the group consisting of D170, D175, E360, D361, D365, D384, Y387, N388, N391, H392, D395, Y398, E399, E419, E422, E430, S433 and S434 of SEQ ID NO: 1 or the corresponding amino acid residue in orthologous polypeptides, wherein binding of said nanobody to said insect CDA confers an insect control activity to said nanobody.

3. The nanobody of claim 2, wherein said non-liner epitope of said insect CDA comprises all of said amino acid residues.

4. The nanobody of claim 2, wherein said amino acid residue is selected from the group consisting of E360, D361, D365, D384, Y387, N388, N391, H392, D395, Y398, E399, E419, E422, E430, S433 and S434 of said SEQ ID NO: 1 or said corresponding amino acid residue in said orthologous polypeptides.

5. The nanobody of claim 2, wherein said non-liner epitope of said insect CDA comprises said amino acid residues E360, D361, D365, D384, Y387, N388, N391, H392, D395, Y398, E399, E419, E422, E430, S433 and S434 of said SEQ ID NO: 1 or said corresponding amino acid residue in said orthologous polypeptides.

6. The nanobody of claim 2, wherein said non-liner epitope of said insect CDA comprises said amino acid residues E360, D361, D365, D384, H392, E419 and E422 of said SEQ ID NO: 1 or said corresponding amino acid residue in said orthologous polypeptides.

7. A nanobody which specifically binds to a non-linear epitope of insect CDA, said non-linear epitope comprises an amino acid residue selected from the group consisting of V22, E23, L24, C25, D46, 148, 168, E99, P100, L101, C102, R286, A287, G293, G294, N295, N296, Q297, M301, E302, E303, Q304, L307, Y308, D309, S310, T311, 1312, P319, P320, P323, Y 324, T325, Y327, F328, H332, R333, C334, H335, G336, N337, L338, Q339, S340, C341, P342, T343,R344, W349, E350, M351, V352, N354, E355, D357, R358, E360, P362, N364, E366, M373, V374, D375, N391, H392, D395, Y398, E399, A403, P404, L405, G406, R415, S434, M443, T444, Q445, V446, 1447, Q448, P475, C477, W478, V479, P480, S482, C483, K484, L485, T499, C500, V501, R502, P508, L510, N511, D512, D516, G517, H518 and Y519 of SEQ ID NO: 1 or the corresponding amino acid residue in orthologous polypeptides, wherein binding of said nanobody to said insect CDA confers an insect control activity to said nanobody.

8. The nanobody of claim 7, wherein said non-liner epitope of said insect CDA comprises all of said amino acid residues.

9. The nanobody of claim 7, wherein said amino acid residue is selected from the group consisting of W349, E350, M351, V352, N354, E355, D357, R358, E360, P362, N364, E366, M373, V374, D375, N391, H392, D395, Y398, E399, A403, P404, L405, G406, R415, S434, M443, T444, Q445, V446, 1447 and Q448, of said SEQ ID NO: 1 or said corresponding amino acid residue in said orthologous polypeptides.

10. The nanobody of claim 7, wherein said non-liner epitope of said insect CDA comprises said amino acid residues W349, E350, M351, V352, N354, E355, D357, R358, E360, P362, N364, E366, M373, V374, D375, N391, H392, D395, Y398, E399, A403, P404, L405, G406, R415, S434, M443, T444, Q445, V446, 1447 and Q448 of said SEQ ID NO: 1 or said corresponding amino acid residue in said orthologous polypeptides.

11. The nanobody of claim 7, wherein said amino acid residue is selected from the group consisting of C25, D46, 148, 168 of said SEQ ID NO: 1 or said corresponding amino acid residue in said orthologous polypeptides.

12. The nanobody of claim 2, wherein said non-liner epitope of said insect CDA comprises said amino acid residues C25, D46, 148, 168 of said SEQ ID NO: 1 or said corresponding amino acid residue in said orthologous polypeptides.

13. The nanobody of claim 7, wherein said non-liner epitope of said insect CDA comprises said amino acid residues E350, M351 and V352 of said SEQ ID NO: 1 or said corresponding amino acid residue in said orthologous polypeptides.

14. A nanobody which specifically binds to an insect CDA, said nanobody comprises three complementarity determining regions (CDRs) as set forth in SEQ ID NOs: 3-5, 7-9, 11-13, 15-17, 19-21, 23-25, 27-29, 31-33, 35-37, 39-41, 43-45, 47-49, 51-53, 55-57, 59-61, 63-65, 67- 69, 71-73, 75-77, 79-81, 83-85, 87-89, 91-93, 95-97, 99-101, 103-105, 107-109, 111-113, 115- 117, 119-121, 123-125, 127-129, 131-133, 135-137, 139-141, 143-145, 147-149, 151-153, 155- 157, or 159-161 arranged in a sequential order from N to C on said nanobody, wherein binding of said nanobody to said insect CDA confers an insect control activity to said nanobody.

15. The nanobody of claim 14, wherein said nanobody comprises three CDRs as set forth in said SEQ ID NOs: 15-17, 83-85 or 95-97 arranged in a sequential order from N to C on said nanobody.

16. The nanobody of anyone of claims 1-6 and 14, wherein said nanobody comprises three CDRs as set forth in SEQ ID NOs: 15-17 arranged in a sequential order from N to C on said nanobody.

17. The nanobody of anyone of claims 7-13 and 14, wherein said nanobody comprises three CDRs as set forth in SEQ ID NOs: 83-85 arranged in a sequential order from N to C on said nanobody.

18. The nanobody of any one of claims 1-17, further comprising a heterologous toxin moiety having an insect control activity.

19. The nanobody of anyone of claims 1-18, wherein said nanobody downregulates activity of said insect CDA.

20. A polynucleotide encoding the nanobody of any one of claims 1-19.

21. A nucleic acid construct comprising the polynucleotide of claim 20 and a cis-acting regulatory element for directing expression of said polynucleotide.

22. A host cell comprising the nanobody of any of claims 1-19 or a polynucleotide or a nucleic acid construct encoding it.

23. A method of producing an insect control nanobody, the method comprising culturing the cell of claim 22.

24. The method of claim 23, comprising isolating the nanobody.

25. A method of insect control, the method comprising contacting the insect with the nanobody of any one of claims 1-19, a polynucleotide or a nucleic acid construct encoding same or a host cell expressing same.

26. The method of claim 25, wherein said contacting comprises applying the nanobody directly to the insect.

27. The method of claim 25, wherein said contacting comprises applying the nanobody to an organism or a surface, which may be in contact with said insect.

28. The nanobody of anyone of claims 1-19 or the method of any one of claims 25-27, wherein said nanobody is formulated for delivery by spraying, irrigation and / or fumigation.

29. The nanobody or the method of any one of claims 1-19 and 25-28, wherein said nanobody is formulated as a liquid formulation.

30. The nanobody or the method of any one of claims 1-19 and 25-28, wherein said nanobody is formulated as a dry formulation.

31. A plant comprising the nanobody of any one of claims 1-19 or a polynucleotide or a nucleic acid construct encoding same.

32. The plant of claim 31 , being a transgenic plant.

33. A commodity product comprising the nanobody of any one of claims 1-19.

34. The commodity product of claim 33, wherein said commodity product is produced from the plant of any one of claims 31-32.

35. The nanobody, the polynucleotide, the nucleic acid construct, the host cell, the plant, the product or the method of any one of claims 1-34, wherein said insect is selected from the group consisting of moth, whitefly, aphid, stinkbug, hopper, beetle and honeybee.

36. The nanobody, the polynucleotide, the nucleic acid construct, the host cell, the plant, the product or the method of any one of claims 1-34, wherein said insect is a moth.

37. The nanobody, the polynucleotide, the nucleic acid construct, the host cell, the plant, the product or the method of any one of claims 35-36, wherein said moth is Spodoptera frugiperda.

38. The nanobody, the polynucleotide, the nucleic acid construct, the host cell, the plant, the product or the method of any one of claims 1-34, wherein said insect is a whitefly.

39. The nanobody, the polynucleotide, the nucleic acid construct, the host cell, the plant, the product or the method of any one of claims 35 and 38, wherein said whitefly is Bemisia tabaci.

40. The nanobody, the polynucleotide, the nucleic acid construct, the host cell, the plant, the product or the method of any one of claims 1-34, wherein said insect is an aphid.

41. The nanobody, the polynucleotide, the nucleic acid construct, the host cell, the plant, the product or the method of any one of claims 35 and 40, wherein said aphid is Myzus persicae.

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