Methods of administering and manufacturing toxic compounds

Abstract

The present invention provides methods for cleaving a SNARE protein by administering an RNA molecule that encodes the light chain of botulinum toxin. The invention also provides pharmaceutical compositions and formulations for administering the therapeutic molecules of the invention. In one embodiment the therapeutic molecule can be an RNA molecule encoding the light chain of botulinum toxin comprised in a lipid nanoparticle, liposome, or solid lipid nanoparticle. The methods can administer the compositions for a variety of therapeutic and cosmetic purposes. The invention also provides methods of synthesizing a toxic substance, for example botulinum toxin.

Description

Methods for Administering and Manufacturing Toxic Compounds Field of the Invention

[0001] The invention involves methods for administering and manufacturing toxic compounds and compositions containing same. Background of the Invention

[0002] A number of bacteria or animals utilize a toxin either as a defense mechanism or as a biproduct of their metabolism. The toxin may be injected into the attacker resulting in pain or even fatal consequences. These toxins often exist in the form of polypeptides. While hundreds of such deadly substances exist, humans have been adept at harnessing their power and converting them into useful medicines that can be administered in very small amounts. Examples include botulinum toxin, snake toxin, scorpion toxin, sea anemone toxin, and leech toxin to name only a few examples.

[0003] Botulinum neurotoxin type-A (BoNT-A) blocks or interferes with or reduces or blocks the release of acetylcholine from peripheral cholinergic nerve terminals, which can occur as a result of the cleavage of SNAP-25. Acetylcholine is a chemical messenger that allows nerves to signal muscles to contract. Thus, botulinum toxin can cause muscles to relax or weaken, or become paralyzed (temporarily). Botulinum toxin is used beneficially for the treatment of disorders characterized by excessive cholinergic neuronal activity. But numerous difficulties arise in administering or manufacturing such compounds. For example, the manufacture of many such compounds is subjected to stringent government regulations, often greatly inflating the cost of producing these toxic drug substances. Botulinum toxin specifically, is a highly potent neurotoxin produced by the Clostridium botulinum and has been used for cosmetic and therapeutic purposes since the 1970s. Cosmetic botulinum toxin is utilized for the improvement of facial wrinkle such as lines appearing between and around the eyebrows, canthal lines (or “crows feet”) on the sides of the eyes, and forehead horizontal lines. Injected botulinum prevents a muscle from moving for a limited time and thus smooths wrinkles on the face.

[0004] It would be very useful to have methods and compositions for efficiently administering botulinum toxin to patients needing their therapeutic or cosmetic effects. It wouldalso be very useful to have more efficient but still safe methods for producing these substances while minimizing the biohazard issues presented, and also for administering the substances as useful medicines. Summary of the Invention

[0005] In one embodiment the present invention provides methods for cleaving a SNARE protein by administering an RNA molecule that encodes the light chain of botulinum toxin (BoNT). In another embodiment the invention provides pharmaceutical compositions and formulations for administering the therapeutic molecules of the invention. In one embodiment the therapeutic molecule can be an RNA molecule described herein comprised in a lipid nanoparticle, liposome, or solid lipid nanoparticle. The methods can administer the compositions for a variety of therapeutic and cosmetic purposes. The invention also provides methods of synthesizing a toxic substance, for example botulinum toxin. The methods can involve synthesizing non-toxic portions of the toxic substance in facilities that are therefore free of stringent government safety regulations for production of toxic substances, for example the light chain or the heavy chain of botulinum toxin, which are non-toxic by themselves. These non-toxic portions can later be formed into the toxic substance in a laboratory in full compliance with stringent government safety regulations regarding the production and handling of toxic substances such as botulinum toxin. These methods are therefore significantly less costly than synthesis that must occur entirely under the safety regulations.

[0006] In a first aspect the invention provides methods of cleaving a SNARE protein. The methods involve administering to a patient a composition described herein containing an RNA molecule encoding the light chain of botulinum toxin to thereby cleave a SNARE protein. In various embodiments the SNARE protein can be SNAP-25, VAMP-2, or syntaxin.

[0007] In another aspect the invention provides a method of cleaving a SNARE protein in a cell, for example in a mammalian cell. The method involves a step of providing to the cell a composition described herein comprising an RNA molecule encoding the light chain of botulinum toxin to thereby cleave the SNARE protein. In any of the embodiments the RNA molecule can be any described herein or a variant thereof. In any of the embodiments the SNARE protein can be SNAP-25 and / or syntaxin and, optionally, VAMP-2.

[0008] In another aspect the invention provides A method of cleaving a SNARE protein in a patient. The method involves administering to the patient a composition comprising an RNA molecule encoding the light chain of botulinum toxin to thereby cleave a SNARE protein.

[0009] In any of the embodiments above the pharmaceutically acceptable carrier can be a lipid nanoparticle. The SNARE protein can be SNAP-25 or syntaxin, or optionally VAMP-2. In any embodiment the composition can be administered by intra-muscular administration or injection. In various embodiments the muscle can be a facial muscle, or a head or neck muscle. In any embodiment the method can be applied for the purpose of wrinkle reduction, or for the treatment of migraine headaches, urinary incontinence, or cervical dystonia. In another embodiment the composition can be administered intra-dermally, optionally into the intra-dermal space, and for the treatment of a condition selected from the group consisting of: excessive sweating, wound healing, rosacea, scarring.

[0010] In any of the embodiments described herein the RNA molecule can be administered in a lipid nanoparticle, but in some embodiments the RNA molecule can be administered in a liposome or in a solid lipid nanoparticle, or as naked RNA.

[0011] In various embodiments the RNA molecule can encode a light chain of botulinum toxin having at least 90% sequence identity to a polypeptide sequence of any one of SEQ ID NO: 29-56 or a variant of any. In some embodiments the composition is administered by injection, or by needle-free injection.

[0012] In any of the embodiments described herein the composition does not comprise (or is free of) an RNA molecule encoding a polypeptide sequence of the heavy chain of botulinum toxin, and / or can not contain (or can lack) a polypeptide sequence of the heavy chain of botulinum toxin.

[0013] In any of the methods the composition can be administered to a human patient.

[0014] In another aspect the invention provides a pharmaceutical composition containing an RNA molecule encoding a light chain of botulinum toxin. In any of the embodiments of the pharmaceutical composition the RNA molecule can be comprised in a lipid nanoparticle. In one embodiment the RNA molecule encodes a polypeptide having at least 90% sequence identity toany one of SEQ ID NOs: 29-56, or a variant of any. In any embodiment of the pharmaceutical composition the composition can not comprise (or lack) RNA encoding for the heavy chain of botulinum toxin.

[0015] In some embodiments the pharmaceutical composition can contain a lipid nanoparticle containing SM-102, polyethylene glycol [PEG] 2000 dimyristoyl glycerol (DMG), cholesterol, and 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC). In another embodiment the lipid nanoparticle can further contain stabilizers selected from the group consisting of: tromethamine, tromethamine hydrochloride, acetic acid, sodium acetate, and sucrose. In another embodiment the pharmaceutical composition can contain a lipid nanoparticle containing (4- hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2hexyldecanoate), 2 [(polyethylene glycol)- 2000]-N,N-ditetradecylacetamide, 1,2-distearoyl-sn-glycero-3-phosphocholine, and cholesterol), tromethamine, and tromethamine hydrochloride.

[0016] In any embodiment the pharmaceutical composition can contain lipid nanoparticles having an average diameter between 86-104 nm. In any embodiment the RNA molecule in the composition can contain a sequence having at least 90% sequence identity to any one of SEQ ID NOs: 85-112 or a variant of any.

[0017] In another aspect the invention provides method of blocking a muscle contraction involving administering a composition containing an RNA molecule encoding the light chain of botulinum toxin to the target muscle. In any embodiment the RNA molecule can be an RNA molecule disclosed herein, (e.g. any one of SEQ ID NO: 29-56 or a variant of any). The RNA molecule can be a sequence transcribed from any one or more of the DNA sequences disclosed herein (e.g. SEQ ID NOs: 1-28 or a variant of any), with or without introns, that encode the light chain of botulinum toxin. In any embodiment the RNA molecule can be contained in a pharmaceutically acceptable carrier or formulation, e.g. encapsulated in a lipid nanoparticle, solid lipid nanoparticles, or nanostructured lipid carriers. In some embodiments the muscle can be a facial muscle, a head, or a neck muscle. In various embodiments the methods can involve administering the composition for cosmetic purposes for treating the appearance of wrinkles in skin, or for treating migraine headaches, sweating, head and / or neck pain, neck pain associatedwith cervical dystonia, or urinary incontinence. In any embodiment the composition can be administered to a human patient.

[0018] In another embodiment the invention provides a method of synthesizing a toxic polypeptide having at least two domains, for example a light chain and a heavy chain. The method involves synthesizing a first domain (e.g. the light chain) of the toxic polypeptide in a first laboratory facility that does not meet the requirements of a government prescribed biosafety level for the toxic polypeptide; and a step of synthesizing a second domain (e.g. the heavy chain) of the toxic polypeptide in a second laboratory facility that does not meet the requirements of the government prescribed biosafety level for the toxic polypeptide; a step of bringing the synthesized domains (e.g. light chain and heavy chain) together in a laboratory that meets the requirements of the government prescribed biosafety level for the toxic polypeptide, to thereby synthesize the toxic polypeptide.

[0019] In one embodiment the step of bringing the light chain and heavy chain together can involve creating a disulfide bond between the heavy chain and the light chain. In any embodiment the light chain can contain a polypeptide of any one of SEQ ID NOs: 29-56 or a variant of any, and the heavy chain can contain a polypeptide of any one of SEQ ID NOs: 57-84, or a variant of any. In one embodiment the toxic polypeptide is botulinum toxin and the government prescribed biosafety level is biosafety level 2. In another embodiment the toxic polypeptide is botulinum toxin and the government prescribed biosafety level is biosafety level 3. In one embodiment the heavy chain and the light chain are produced in separate strains and / or from separate open reading frames. In various embodiments the toxic polypeptide can be selected from the group consisting of: botulinum toxin (BoNT), scorpion toxin, snake toxin, and leech toxin. In one embodiment the toxic polypeptide is botulinum, optionally sub-type A. Brief Description of the Drawings

[0020] Figure 1a provides a graphical illustration of a putative result of a functional activity assay for LC / A showing SNAP-25 cleavage at 2 hours as determined by fluorescence detection. Figure 1b shows the same at 18 hours.

[0021] Figure 2 provides a graphical illustration of putative results of western blots showing SNAP-25 cleavage from neurons exposed to botulinum toxin.

[0022] Figure 3a provides a graphical illustration of putative results from mouse spinal cord (MSC) cells that are exposed to botulinum toxin. Figure 3b provides a graphical illustration of putative results from rat spinal cord (RSC) cells that are exposed to botulinum toxin. Figure 3c provides a graphical illustration of putative results from iCell neurons that are exposed to botulinum toxin. Figure 3d provides a graphical illustration of putative results from human induced pluripotent (HIP) neurons that are exposed to botulinum toxin. In all cases cell lysates are analyzed for SNAP-25 cleavage by western blotting.

[0023] Figure 4a provides a graphical illustration of cell counts in plasmid DNA transfected Expi293F cells. The graph shows that infection with the plasmid DNA did not substantially harm cell growth. Figure 4b shows cell counts of RNA transfected cells, also showing transfection did not substantially harm cell growth.

[0024] Figure 5a presents flow cytometry analysis for pDNA transfected Expi293F cells for the “no DNA” control and the Green Lantern samples. The analysis shows that the plasmids are present and active in the cells. Figure 5b shows flow cytometry analysis for mRNA transfected 293F cells. The analysis is presented in both high and low amounts of the transfection vehicle. The graphs illustrate that both the high amount and low amount transfection achieved expression in the cells.

[0025] Figure 6a is a Western blot showing the presence of rBoNT in the cells of pDNA transfected strains. Lane M: markers; Lane 1: 2ng rBoNT-LC_A; Lane 2: 5 ng rBoNT-LC_A; Lanes 3-4: No DNA controls; Lanes 5-6: Green Lantern (10 ug); Lanes 7-8: LC_A1 Hall strain (10 ug). Figure 6b shows a Western blot of LC_A1 Hall strain pDNA transfected strains. Figure 6c shows a Western blot analysis for LC_A1_Hall strain mRNA transfected cells using Messenger Max® (Life Technologies, Carlsbad, CA) transfection vehicle.

[0026] Figure 7a shows the cell count data (x10e6 / ml) for pDNA and mRNA expression for various serotypes of the light chain of botulinum toxin. Figure 7b shows the percent viable cells for pDNA and mRNA expression for various strains of the light chain of botulinum toxin.

[0027] Figure 8a presents a Western blot for the expression of polypeptides for LC subtypes A1 and A2. Figure 8b presents a Western blot for the expression of light chain serotypes E and C. Figure 8c presents a bar graph showing the amounts of each light chain variant expressed from mRNA or pDNA.

[0028] Figure 9a is a graphical illustration of mRNA-derived botulinum toxin light chain serotype C exhibiting specific proteolytic cleavage on a syntaxin-mimic substrate over time. Robust increases in fluorescence confirmed substrate cleavage. Figure 9b is a graphical illustration of background corrected endpoint fluorescence.

[0029] Figure 10a is a graphical illustration of mRNA-derived botulinum toxin light chain subtype A1 exhibiting specific proteolytic cleavage on a SNAP-25 mimic peptide substrate over time. Figure 10b is a graphical illustration of mRNA-derived botulinum toxin light chain subtype A2 exhibiting specific proteolytic cleavage on a SNAP-25 mimic peptide substrate over time. The robust decrease in emission ratio clearly demonstrates substrate cleavage. Figure 10c is a graphical illustration of background corrected endpoint emission ratio.

[0030] Figure 11 is a graphical illustration of capillary electrophoresis data for 29 mRNA molecules encoding various light chain subtypes and mutants. Detailed Description of the Invention

[0031] The invention provides methods of modulating SNAP-25 activity in a patient by administering a composition containing an RNA molecule encoding for the light chain of botulinum toxin according to a method disclosed herein. The modulation can involve cleaving the SNAP-25 protein and thereby blocking, interfering with, or reducing the release of acetylcholine.

[0032] While the traditional method of administering a toxic medical substance is in its natural polypeptide form, it was discovered by the present inventors that toxic polypeptide substances can be administered as an RNA molecule encoding only the biologically necessary portion of the toxin into the treated area. The methods offer the advantage of being able to administer the compositions without ever needing to synthesize the toxic polypeptide form of the substance, while still retaining all the advantages of the use of the substance. The inventiontherefore provides compositions containing an RNA molecule encoding the light chain of botulinum toxin as disclosed herein and methods of use.

[0033] The invention also provides methods and compositions having the technical effect of modulating, reducing, or interfering with the activity of a SNARE protein. In any embodiment the SNARE protein can be SNAP-25 (synaptosomal-associated protein-25 kDa), VAMP-2, or syntaxin. SNAP-25 is important for normal neurotransmitter release and is involved in synaptic vesicle fusion. Botulinum toxin interferes with or blocks neurotransmitter release at the neuromuscular junction by cleaving SNAP-25, thus modulating (by blocking, reducing or interfering with) SNAP-25 activity, VAMP-2 activity, or syntaxin activity. The invention also provides methods of modulating (e.g. reducing or interfering with) neuro- secretory signaling in a patient by administering a composition disclosed herein according to a method disclosed herein. In other embodiments the technical effect can be to disrupt the release of neurotransmitters at the neuromuscular junction by cleaving neuronal SNARE proteins SNAP-25 and / or syntaxin, and can have the same effect on VAMP-2.

[0034] In some embodiments the invention provides methods and compositions for blocking a muscle contraction, or methods and compositions for administering a toxic substance that blocks a muscle contraction.

[0035] The invention also provides methods of synthesizing toxic polypeptides in the polypeptide form of the substances. By synthesizing non-toxic portions or sub-units of the toxin, one is able to obviate the need to perform all synthesis in a laboratory in compliance with applicable government regulations, such as regulations associated with the assigned biosafety level for the synthesized toxic substance. When the non-toxic portions are synthesized, they can then be brought together in a laboratory in full compliance with the indicated government regulations. The methods therefore offer the ability to reduce reliance on such high security laboratories, and therefore significantly reduce the costs of producing the substances and reduce costs to the patient.

[0036] The term therapeutic molecule refers to proteins, polypeptides, DNA molecules, and RNA molecules that are utilized to target and treat diseases, disorders, or conditions. While therapeutic toxic polypeptides have been administered in the full polypeptide form, the presentinventors discovered that the therapeutic benefits of toxic polypeptides can be realized by administering only an RNA molecule encoding the toxic polypeptide or an RNA molecule encoding a biologically active portion of the toxic polypeptide. Thus, the inventors discovered that it is not necessary to administer the full form of the polypeptide as is commonly done and believed, but only an RNA molecule encoding a portion or encoding a biologically active sub- portion or sub-unit of the full toxic polypeptide. Thus in some embodiments an RNA molecule encoding a light chain of botulinum toxin is a therapeutic molecule. Therapeutic benefit refers to having effectiveness in alleviation of a condition disclosed herein.

[0037] Biologically active means the molecule has a desired therapeutic or cosmetic effect applied through the target. In some embodiments the target in the present invention can be a muscle, and the therapeutic effect can be disruption, blocking, interference with, or reduction of a nerve signal to a muscle, which can lead to weakness or paralysis of the muscle (which can be temporary). In some embodiments the biological activity is the temporary paralysis or relaxing or weakening of muscles that cause wrinkles. Botulinum toxin can thus prevent such muscles from contracting and creating creases in the skin. In other embodiments the biological activity can be interference with, blocking of, or reduction of a neurotransmitter, which in one embodiment can be acetylcholine (but in other embodiments can include any one or more of endorphins, serotonin, norepinephrine, GABA, glutamate, and dopamine). In various embodiments the biological activity can last for at least 3 months, or for 6 months, for more than 6 months, or for from 3 to 6 months. Botulinum toxin (BoNT)

[0038] BoNTs are a family of polypeptides produced by C. botulinum. BoNTs are synthetized as a single-chain polypeptide of approximately 150^kDa that is cleaved by a protease into dichain polypeptides linked by a disulfide bond. The dichain polypeptide can be composed of a 50^kDa light chain (LC) with zinc-dependent protease activity and a 100^kDa heavy chain (HC) with an N-terminal translocation domain (Hn) and a C-terminal cell binding domain.

[0039] In one embodiment of the methods the toxic polypeptide is a botulinum toxin (BoNT), or a variant thereof. Botulinum toxin is a neuromodulator and is utilized to block the release of neurotransmitters (e.g. acetylcholine), into the synaptic cleft, or to block musclecontractions (or cause muscle paralysis), and many therapeutic benefits have been associated with this effect for treating conditions disclosed herein. Thus, BoNT has been utilized to treat various conditions by intra-muscular administration (e.g. by intra-muscular injection, NFI, or topical administration), such as chronic migraine headaches (e.g. administration into head and neck muscles), spastic disorders (administration into affected muscles), cervical dystonia (e.g. by administration into neck muscles), and detrusor hyperactivity (e.g. administration to detrusor muscle), blepharospasm (administration into eyelid muscles), glabellar lines or lateral canthal lines (administration into facial muscles), forehead lines (administration into forehead muscles) – and the present methods can compositions can be useful for treating these conditions too through the same administration. Presently there are three approved Type A botulinum toxins available on the US market (Botox® (Allergan, Inc., Irvine CA), Dysport® (Ipsen Biopharm, Ltd, Wrexham, UK), and Xeomin® (Merz Pharma GmbH, Frankfurt am Main, Germany)), and one Type B botulinum toxin (Myobloc® (Solstice Neurosciences LLC, Louisville, KY)). In various embodiments of the present invention the light chain (LC) can have any light chain polypeptide sequence described herein or a variant of any (e.g. one of SEQ ID NOs: 29-56 or 120-124, or a variant of any), and the heavy chain can have any heavy chain polypeptide sequence described herein or a variant of any (e.g. one of SEQ ID NOs: 57-84, or a variant of any).

[0040] In the cytoplasm of a cell botulinum toxin cleaves SNARE proteins (synaptosomal-associated protein), which mediate vesicle fusion with their target membrane bound compartments). SNAP-25 is a SNARE protein that helps to stabilize the SNARE complex and facilitate vesicle fusion. Upon cleavage of SNARE proteins, acetylcholine release is inhibited at the neuromuscular junction, thus reducing or stopping nerve signaling and leading to muscle weakness or paralysis.

[0041] BoNT serotype A (BoNT / A) is synthesized as a single chain protein of about 1296 amino acid residues and cleaves SNAP-25, thereby blocking synaptic vesicle exocytosis. Botulinum serotype-A (BoNT / A) is commonly used in various medical applications described herein. Serotype A and serotype E bind to and cleave the 25 kD SNARE protein (SNAP-25), whereas serotype B (rimabotulinum toxin B) binds to and cleaves “VAMP-2” (vesicle associate membrane protein). Botulinum serotype C cleaves both SNARE proteins SNAP-25 andsyntaxin. By cleaving these proteins BoNTs disrupt the process of vesicle docking and fusion at the synapse that would otherwise lead to the release of neurotransmitters.

[0042] The present inventors discovered that BoNT can be effectively administered to cleave a SNARE protein, or inhibit or block a muscle contraction by administering a composition containing an RNA molecule encoding the light chain of BoNT into a muscle, e.g. a facial, head, or neck muscle. In one embodiment the composition contains an RNA molecule encoding any botulinum toxin light chain polypeptide disclosed herein or a variant of any, for example a sequence of any one of SEQ ID NO: 29-56 or a variant of any, or any one of SEQ ID NO: 120-125 or a variant of any. The composition can contain an RNA molecule of any sequence disclosed herein, for example any one of SEQ ID NO: 85-113, or a variant of any; or the composition can contain an RNA molecule of any one of SEQ ID NO: 114-117, or a variant of any. The composition can also contain an RNA molecule encoded by a DNA sequence of any one of SEQ ID NOs: 1-28 or a variant of any. In any embodiment the RNA molecule can be present in a pharmaceutically acceptable carrier. In any embodiment the BoNT utilized in the invention can be serotype-A (BoNT / A), and / or serotype B (BoNT / B), and / or serotype BoNT / C, and / or serotype BoNT / D, and / or serotype BoNT / E, and / or serotype BoNT, F, and / or serotype BoNT / G, or sub-types of any, in all possible combinations and sub-combination. In any embodiment the BoNT utilized in the methods and compositions of the invention can be serotypes BoNT / A, BoNT / C, and BoNT / E. In various embodiments the compositions of the invention can be administered inra-muscularly to any one or more of the glabellar muscles, the corrugator supercilii, the depressor supercilii, the procerus muscles, the medial fibers of orbicularis oculi muscles, the frontalis muscle, and the upper facial muscles, all of which are helpful for treating skin wrinkles.

[0043] In any embodiment the methods and compositions of the invention can contain and utilize RNA or self-replicating RNA (srRNA), which can encode any BoNT light chain polypeptide sequence described herein or a variant of any (e.g. one of SEQ ID NOs: 29-56 or a variant of any). srRNA additionally can contain one or more genes that allow it to replicate itself within the cytoplasm of a cell (e.g. one or more replicases, and / or one or more RNA-dependent RNA polymerases), leading to increased expression of the encoded polypeptide, in addition to containing a light chain of botulin toxin disclosed herein. The genes or sequences can becomprised on an RNA construct. In some embodiments srRNA can also incorporate ribozymes, which are RNA molecules with catalytic activity. The ribozymes can have active sites where the replication process occurs. In some embodiments the srRNA molecules can contain 2’-5’ phosphodiester bonds, which help prevent the formation of inactive complexes.

[0044] The RNA or srRNA molecule utilized in the invention can be a linear, single- stranded RNA or srRNA molecule. In any of the embodiments the RNA or srRNA can include a 5′ cap, and / or a 3′ polyA tail. The RNA or srRNA can also (optionally) include a 5′ and / or 3′ UTR. In some embodiments the RNA or srRNA can also encode non-structural proteins. In various embodiments when an srRNA is utilized, it can be derived from a positive-strand RNA virus (e.g. an alphavirus such as VEEV (Venezuelan equine encephalitus virus) or EEEV (eastern equine encephalitis virus)) having one or more structural proteins removed and replaced with an RNA molecule encoding a light chain botulinum disclosed herein. In any embodiment an srRNA molecule of the invention can encode one or more replicase genes, which can facilitate amplification of the payload RNA upon delivery. In some embodiments the RNA or srRNA can be greater than about 8,000 nt in length, or 8,000-10,000 nt in length, or 8,000-11,000 nt in length, or about 10,000 nucleotides in length. In any embodiment the RNA or srRNA can be comprised within an lipid nanoparticle, liposome, or solid lipid nanoparticle described herein to deliver the RNA or srRNA payload. In some embodiments the use of srRNA can allow the formulation to be administered at a lower dose. In some embodiments the RNA or srRNA of the invention can additionally encode any one or more of 5’ and 3’ CSE sequences, nsP1-4 genes, a sub-genomic promoter, and any BoNT light chain of botulinum disclosed herein (or a variant of any).

[0045] In any embodiment the RNA or srRNA molecule comprised in the compositions and formulations of the invention can optionally include one or more modified nucleotides or nucleotide analogs. For example the RNA or srRNA can include one or more N1-methyl pseudouridine nucleoside(s), and / or one or more N1-methylpsuedouridine-5’-triphosphate(s) (or the trisodium salt). In addition to or instead of the N1-methylpseudouridine, the RNA or srRNA can include one or more 5-methylcytidine-5’-triphosphate(s) nucleosides. In other embodiments the RNA or srRNA can also contain (in addition to or instead of the othernucleotide analogs) a pseudouridine 5’ triphosphate, or a 5-methyoxy-uridine-5’-triphosphate. In any embodiment the modified nucleosides can substitute for one or more uridine nucleosides.

[0046] In some embodiments the mRNA or srRNA can have modified 5’ and 3’ untranslated regions (UTRs) flanking the coding sequence. In various embodiments UTRs can be selected from endogenously found proteins with long half-lives that lack active mRNA synthesis (e.g. alpha- and beta-globulins). The RNA can also have a poly-A tail (e.g.60-150 nucleotides) and a 5’ cap, which can enhance its translation into proteins within cells.

[0047] In any embodiment the dose of RNA administered to a patient can be from 0.1 ug to about 10 ug, or from 20-30 ug of RNA, or from 20-35 ug of RNA per dose, or from 50-75 ug of RNA per dose, or from 75-125 ug of RNA per dose. Persons of ordinary skill in the art with resort to this disclosure will realize that the precise dose selected will depend on the specific application and the specific form of RNA formulated. Other Toxins

[0048] While the invention may be most easily applicable to toxic substances having a polypeptide structure, the invention includes compositions and methods relating to other types of toxic substances. Thus, in some embodiments the toxic substance may have a polypeptide portion and a non-polypeptide portion. For example, the scorpion toxin is a protein found in the venom of scorpions and the covalent structures of several such toxins has been deduced. The toxin is comprised of around 66 amino acid residues forming a three stranded anti-parallel beta sheet over which lies an alpha helix of approximately three turns, which are stabilized by four disulfide bridges that cross-link the long-chain toxins, whereas the short toxins can contain only three. Other toxins that can also be synthesized and / or administered using the methods disclosed herein include snake toxin, sea anemone toxin, and leech toxin. Thus, the compositions and methods of the invention can be applied with toxic medically useful substances that are not polypeptides, or not entirely polypeptides. The invention can be applied to any toxic medical composition comprising non-toxic portions that can be synthesized separately and efficiently combined in a compliant laboratory, and the methods of the invention can also be applied using these compositions.Methods

[0049] The invention provides methods of cleaving a SNARE protein or of modulating (e.g. reducing) SNAP-25 signaling in a patient by administering a composition or formulation described herein. The cleaving or modulation can be performed by cleaving a SNARE protein (e.g. SNAP-25) and thereby blocking, interfering with, or reducing neurotransmitter signaling (e.g. by interfering with the release of acetylcholine at the neuromuscular junction), which can be achieved with intra-muscular or intra-dermal administration. In any embodiment the compositions or formulations can contain an RNA molecule described herein or a variant of any encoding the light chain of botulinum toxin to a muscle (e.g. any one of SEQ ID NO: 29-54 or 120-124, or a variant of any). In any embodiment administration of a composition of the invention can be performed by intra-muscular administration (e.g. by injection, NFI, or topical administration) to treat wrinkles, migraines, cervical dystonia, urinary incontinence, skin and / or neck wrinkles, headaches, wound healing, arthritis, chronic back pain, chronic neck pain, myofascial syndrome, and other types of pain.

[0050] In other embodiments the compositions can be administered intra-dermally (e.g. into the intra-dermal space). Intra-dermal administration can be by injection, NFI, or topical administration, or any method described herein for applications such as facial rejuvenation, hyperhidrosis (excessive sweating), or for treating pain (e.g. cervical dystonia), rosacea, scarring (e.g. hypertrophic or keloid scars), skin wrinkle reduction, or for promoting wound healing. In some embodiments the compositions can be administered by intra-dermal injection, which can be performed using a standard 30g hypodermic needle, but persons of ordinary skill with resort to this disclosure will realize that many options in needles exist, for example small diameter needles or micro-needles may be preferable to achieve a higher level of non-invasiveness. Examples include, but are not limited to a 33-gauge, 31-gauge, 27-gauge, 28-gauge needle, or a 0.2mm x 0.9mm needle. Needles can be made of conventional materials known to persons of ordinary skill in the art, such as surgical steel. Needle-free injection or topical administration can be utilized for administration in these applications also.

[0051] In other embodiments the invention provides a method of cleaving a SNARE protein in a patient by administering a composition or formulation described herein according toany method described herein. In any embodiment the SNARE protein can be SNAP-25 or VAMP-2.

[0052] In any embodiment the compositions can be administered by needle-free injection (NFI) technology for drug delivery. This group of technologies can deliver therapeutic compositions by driving drugs through the skin by, for example, by Lorentz forces, shock waves, pressure by gas or electrophoresis (propelling the drug through the skin), or other needle-free technologies. Needle-free injection technology uses a high-pressure source to form high-speed liquid jets that penetrate the dermal layers and deliver drugs with a greater contact area between injected liquid and delivers the drug into the intra-muscular layer. The bulk of liquid delivered is gradually absorbed, resulting in better drug absorption and reduced pain on injection.

[0053] In any embodiment administration can be performed by topical administration, for example by simply applying a composition of the invention to the surface of the skin above the targeted muscle or tissues in a pharmaceutically acceptable carrier. The composition can penetrate the skin and tissues it is applied to and reach the target muscle (or nerve) and block or prevent a muscle contraction (or neurotransmitter).

[0054] The RNA molecules contained in the compositions of the invention can encode a botulinum light chain polypeptide disclosed herein or a variant of any of them (e.g. an RNA molecule encoding a botulinum light chain polypeptide having at least 90%, or at least 95%, or at least 97%, or at least 98%, or at least 99% sequence identity to any one of SEQ ID NO: 29-56 or 120-124). In other embodiments the RNA molecules contained in the composition can have a sequence transcribed from any DNA sequence described herein or a variant of any, e.g. one or more of the SEQ ID NOs: 1-28 or 127, or a variant of any. In any embodiment the RNA molecules can be mRNA. Persons of ordinary skill with resort to this disclosure will realize that other RNA sequences can also be utilized, e.g. humanized sequences, or sequences optimized for expression in a microorganism, or unmodified sequences. The RNA sequences can also be from any strain of Clostridium botulinum, or can be expressed from variants thereof.

[0055] The invention provides the compositions disclosed herein for use in the treatment of the human or animal body by therapy, as disclosed herein. The compositions and methods can be for use in treating one or more conditions in a patient selected from: skin or facial wrinkles,migraines, cervical dystonia, other types of pain, urinary incontinence, facial rejuvenation, hyperhidrosis (excessive sweating), rosacea, to reduce or improve scarring (e.g. hypertrophic or keloid scars), or for promoting wound healing, or for treating any condition described herein, which treatments can be administered as described herein. In any embodiment the patient can be a human. The invention also provides any of the compositions described herein for use as a medicament, which can be for the treatment of any disease, disorder, or condition described herein. Compositions

[0056] In some embodiments the compositions of the invention can contain one or more RNA molecules disclosed herein, which can be formulated within a lipid-based formulation, for example a lipid nanoparticle (LNP), liposome, or solid lipid nanoparticle. LNPs are an effective means for administering therapeutic RNA and mRNA molecules. LNPs can protect the RNA from nucleases, biological uptake and other biological threats (e.g. the mononuclear phagocyte system), and also enhance the RNA ability to reach target tissues. Persons of ordinary skill with resort to this disclosure will realize processes for formulating the RNA molecules described herein into LNPs. In various embodiments the LNPs may contain cholesterol or PEG-lipids, for example to increase LNP stability and prolong blood circulation times. When PEG-lipids are used in some embodiments they can comprise one or more of, for example, PEG-2000, PEG- 2000 derivatives, 1,2-dimyristoyl-rac-glycero-3-methoxypolyethylene glycol-2000 (PEG2000- DMG), or 1,2-distearoyl-rac-glycero-3-methoxypolyethylene glycol-2000 (PEG2000-DSG), or other neutral PEG-lipids. In various embodiments the length of their saturated alkyl chains of the PEG-lipids can be, for example, C14 or C18. In other embodiments the RNA molecules of the invention can be formulated in other lipid-based formulations such as liposomes, solid lipid nanoparticles, or within lipoplexing agents, or within a cationic polymer / lipid formulation. Other embodiments can involve formulation in elastic liposomes, or nanostructured lipid carriers, “lipobrids” and lipid-polymer nanoparticles. Other methods can include formulation with lipids, lipid-like materials, lipidoids (ionizable lipid derivatives composed of tertiary amines), polymers, and even protein derivatives. Additional methods are known to persons of ordinary skill in the art and will be realized by those having resort to this disclosure.

[0057] In various embodiments the pharmaceutical compositions and formulations of the invention can contain any therapeutic molecule described herein. In some embodiments therapeutic molecules can be any one or more RNA molecules (encoding a botulinum polypeptide) described herein or a variant of any (e.g. an RNA of any one of SEQ ID NOs: 85- 118 or a variant of any), which can optionally be comprised in a lipid nanoparticle, liposome, or solid lipid nanoparticle described herein, or as naked RNA (i.e. RNA not encapsulated in a lipid nanoparticle, liposome, or solid lipid nanoparticle, or other vesicle or protective structure). In some embodiments the composition comprises an RNA molecule encoding a botulinum light chain polypeptide disclosed herein or a variant of any, e.g. of any one of SEQ ID NO: 29-56 or 120-124 or a variant polypeptide of any. In some embodiments the composition comprises an RNA molecule (encoding a botulinum light chain polypeptide) of any one of SEQ ID NO: 114- 118 or a variant of any. As used herein a “variant” of a sequence refers to a sequence having at least 85%, or at least 90%, or at least 95%, or at least 97%, or at least 98%, or at least 99% sequence identity to the reference sequence. In any embodiment the reference sequence can be, for example, any one of SEQ ID NO: 1-127.

[0058] In any embodiment a pharmaceutical composition or formulation of the invention can contain no RNA (or DNA) encoding for the heavy chain of BoNT, or at least less than 10% or less than 5% or less than 1% or less than 0.1% w / w of RNA (or DNA) encoding for a heavy chain of BoNT, or can contain no detectable level of RNA (or DNA) encoding for a heavy chain of BoNT, or contains less than a therapeutic amount. In any embodiment the compositions and formulations of the invention also can contain no polypeptide of the light chain of BoNT and / or can contain no polypeptide of the heavy chain of BoNT, or at least less than 10% or less than 5% or less than 1% or less than 0.1% w / w polypeptide of the heavy chain or light chain of BoNT of any serotype, or contains less than a therapeutic amount. In any embodiment the compositions and formulations of the invention can contain no full length BoNT polypeptide, or at least less than 10% or less than 5% or less than 1% or less than 0.1% w / w polypeptide of the full length BoNT of any serotype, or less than a therapeutic amount. A therapeutic amount is an amount having relevance in the treatment of a condition disclosed herein.

[0059] In some embodiments therapeutic molecules can be RNA molecules encoded by a DNA molecule described herein, e.g. mRNA molecules encoding a BoNT light chain disclosedherein, which can, optionally, be comprised in a lipid nanoparticle, or a liposome, or a solid lipid nanoparticle, or as naked RNA, e.g. any one of SEQ ID NO: 1-28 or 126 or a variant of any.

[0060] The invention also provides formulations and pharmaceutical compositions that can comprise an RNA molecule described herein comprised in a lipid nanoparticle, or in a liposome, or a solid lipid nanoparticle described herein. The composition can also be naked RNA, which can be provided in a pharmaceutically acceptable carrier. In any embodiment the pharmaceutical compositions and formulations of the invention can be contained in a pharmaceutically acceptable carrier, which are compositions that are inert and / or non-toxic to humans. In any embodiment a pharmaceutically acceptable carrier can be aqueous, a liquid, or a semi-liquid suitable for intra-muscular or intra-dermal administration. Such pharmaceutically acceptable carriers can have properties that stabilize the therapeutic molecule (e.g. and protect it from degradation), improve solubility (e.g. in the body’s tissues or fluids), or facilitate absorption (e.g. enhance the rate of absorption into the body’s tissues or cells).

[0061] In some embodiments the pharmaceutically acceptable carrier can be a sterile aqueous solution, such as phosphate buffered saline (PBS), or water-for-injection, or others known to persons of ordinary skill in the art. In various embodiments, the pharmaceutically acceptable carrier can be a buffer (e.g. acetate, citrate, histidine, succinate, phosphate, hydroxymethylaminomethane (Tris)), a preservative, an isotonic agent, a stabilizer, a surfactant, a wetting agent, an emulsifier, an antioxidant, a bulking agent, or a chelating agent, or can contain one or more of the above in a mixture. The pharmaceutically acceptable carrier can contain a pharmaceutically acceptable salt, for example, saline, dextrose, or others known to persons of ordinary skill. Such additional ingredients, of course, should not adversely affect the overall stability of the pharmaceutical formulation of the present invention.

[0062] In any embodiment the pharmaceutical compositions and formulations of the invention can contain BoNT light chain RNA of any serotype, and can also not contain (or be free of) RNA encoding the BoNT heavy chain. In one embodiment the pharmaceutical formulation contains RNA encoding the BoNT light chain of serotype A, and does not contain RNA encoding the BoNT heavy chain (or at least not in the quantities specified herein). Any ofthe pharmaceutical compositions or formulations can be prepared in any manner described herein, e.g. in lipid nanoparticles, liposomes, or solid lipid nanoparticles as described herein. Lipid Nanoparticles (LNPs)

[0063] LNPs can be lipid systems comprising two or more (e.g. three or four) lipids at varying ratios and their structures are known to those of ordinary skill in the art. In general they may form a mix of lipid components having the nucleic acid within the particle interior. The lipids utilized in the compositions and formulations of the invention can contain a polar head group, a hydrophobic tail, and a linker between the two. In any embodiment the LNP can comprise a lipid shell surrounding an internal core composed of reverse micelles that encapsulate a payload molecule (e.g. an RNA molecule). An LNP can have a single lipid layer (monolayer) surrounding a core that can be solid or non-aqueous. The LNP can also be characterized by having an internal core of reverse micelles. LNPs are very efficient for delivering nucleic acid payloads.

[0064] Liposomes are also an important mode of administration and can be useful when specific targeting is desired (e.g. for administration in the treatment of urinary incontinence). Liposomes can have a lipid bilayer with an aqueous internal core. Solid lipid nanoparticles (SLNs) are characterized by having a solid lipid core, which can contain both solid and liquid lipids. The solid lipid core can be made of triglycerides or saturated fatty acids (which can be solid at room temperature). The compositions of the invention can also be formulated in nanostructured lipid carriers, which can have surfactant lipid shells, a lipid bilayer and solid lipids as an internal core.

[0065] In one embodiment the RNA molecules of the invention can be formulated within lipid nanoparticles. LNPs can have a size ranging from <1 um, to 10-40 nm, or 10-50 nm, or 50-150 nm, or 50-100 nm, or 50-150 nm. In any embodiment the lipid nanoparticles of the invention can have a size of 75-115 nm, or 75-100 nm, or 86–104 nm, or 75-85 nm, or 80-100 nm, or about 80 nm. In other embodiments the compositions can comprise lipid nanoparticles where at least 90% or at least 95% or at least 98% of the LPNs are 75-115 nm, or 75-85 nm, or 80-100 nm, or 86-104 nm.

[0066] The lipids comprising the LNP can protect the RNA payload and provide an exterior that facilitates the entry of the RNA into cells. With proper formulation the LNPs can overcome the various extracellular and intracellular obstacles encountered.

[0067] In various embodiments the compositions can be administered by intra-muscular administration or injection, intra-dermal (ID) administration or injection, or by topical administration by simply contacting the formulation with the surface of the skin near or above the target muscle or tissue. In one embodiment the compositions and formulations of the invention can be administered to the intra-dermal space. This can involve administration into the dermis (e.g. just below the epidermis). Intra-dermal administration of the compositions of the invention can result in blocking of, interference with, or reduction in the release of neurotransmitters that regulate pain signaling (e.g. any one or more of endorphins, serotonin, substance P, norepinephrine, GABA, glutamate, and dopamine). The compositions and formulations of the invention can also be administered as naked RNA. Persons of ordinary skill with resort to this disclosure know how LNPs can be formulated, e.g. by mixing a lipid solution with an aqueous RNA solution. Microfluidics can be advantageously used in the formulation process. LNPs can be formulated so that the composition carried is able to penetrate the skin and penetrate underlying (muscle) tissues so that a contraction in a target muscle can be blocked.

[0068] In one embodiment the lipid nanoparticle is a cationic lipid-based transfection reagent. Examples of such a commercially available LNP formulation include Messenger MAX®, Lipofectamine® 2000, and Lipofectamine® 3000 (all from Life Technologies, Inc., Carlsbad, CA) and StemMACS® (Miltenyi Biotec, Germany). But the lipid nanoparticles utilized in the compositions and formulations of the invention can be any suitable lipid nanoparticles. In any embodiment the LNPs can contain a mixture of ionizable lipids, helper lipids (e.g. glycerophospholipids), sterol lipids (e.g. cholesterol), and PEGylated lipids.

[0069] LNPs are known to persons of ordinary skill in the art and are readily formulated. In general, ionizable lipids can be positively charged at low pH, which can facilitate cell uptake and endosomal escape. These lipids can include (but are not limited to) SM-102, ALC-0315, Dlin-MC3-DMA, and DOTAP. Ionizable lipids can complex with the nucleic acid payload and facilitate endosomal escape. Helper lipids (or neutral lipids) facilitate achieving encapsulationand stability of the RNA payload, bilayer integrity, and can include (but are not limited to) DOPE and / or DSPC. Cholesterol also assists in stabilizing the LNP and enhances its stability and permeability, and in some embodiments can be present as DC-cholesterol and / or BHEM- cholesterol. PEGylated lipids have polyethylene glycol (PEG) chain attached and can increase the LNPs circulation time in the bloodstream. These lipids can include (but are not limited to) PEG2000-DMG (or PEG2000-DSG), ALC-0159. Other lipids and lipid mixtures are known to and will be realized by persons of ordinary skill in the art with resort to this disclosure.

[0070] In one embodiment the LNP of the invention can comprise a mixture of (4- hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2hexyldecanoate), 2 [(polyethylene glycol)- 2000]-N,N-ditetradecylacetamide, 1,2-distearoyl-sn-glycero-3-phosphocholine, and cholesterol), tromethamine, tromethamine hydrochloride, and an additive appropriate to assist in the freezing process of the formulation (e.g. sucrose).

[0071] In one embodiment the LNP can comprise a mixture of 2-hexyl-decanoic acid, 1,1’-[[(4-hydroxybutyl)imino]di-6,1-hexanediyl]ester (ALC-0315), 1,2-distearoyl-sn-glycero-3- phosphocholine (DSPC), cholesterol, and alpha-[2-(ditetradecylamino)-2-oxoethyl]omega- methoxy-poly(oxy-1,2-ethanediyl) (ALC-0159). In one embodiment these components can be present in lipid molar ratios of about 46.3:9.4:42.7:1.6, respectively (plus or minus 2%, or 5%, or 10% w / w).

[0072] In one embodiment the LNP of the invention can contain a mixture of SM-102, 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), cholesterol, and polyethylene glycol [PEG] 2000 dimyristoyl glycerol (DMG). In one embodiment these components can be present in a lipid molar ratio of about 50:10:38.5:1.5, respectively (plus or minus 2%, 5%, or 10% w / w).

[0073] In any embodiment the LNP of the invention can also contain stabilizers such as (but not limited to) tromethamine, tromethamine hydrochloride, acetic acid, sodium acetate, and sucrose. In another embodiment the LNP can comprise a mixture of (SM-102, 1,2-dimyristoyl- rac-glycero3-methoxypolyethylene glycol-2000 [PEG2000-DMG], cholesterol, and 1,2- distearoyl-snglycero-3-phosphocholine [DSPC]), and a mixture of stabilizers as above.

[0074] In one embodiment the LNPs of the invention can contain a cationic lipid, a non- cationic lipid, a PEG-lipid. In one embodiment the cationic lipid can be a phospholipid and the non-cationic lipid can be cholesterol. The cationic lipid can also comprise ATX-002. In any embodiment the phospholipid can be any of 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, phosphatidic acid, palmitoyloleoyl phosphatidylcholine, lysophosphatidylcholine, lysophosphatidylethanolamine, dipalmitoylphosphatidylcholine, dioleoylphosphatidylcholine, distearoylphosphatidylcholine and dilinoleoylphosphatidylcholine. In any embodiment the PEG-lipid can be, for example, PEG-diacyl glycerol (PEG-DAG) or PEG-dialkyloxyalkyl (PEG-DAA), or PEG-1,2-dimyristoyl-rac-glycero-3-methoxypolyethylene glycol (PEG-DMG).

[0075] In any embodiment any of the LNP formulations can further contain components to balance the acidity of the body, which can include potassium chloride, monobasic potassium phosphate, sodium chloride, and dibasic sodium phosphate dihydrate. Any of the formulations described herein can also, optionally, contain cholesterol.

[0076] In any of the formulations the person of ordinary skill with resort to this disclosure will realize substitutions can be made. For example, tromethamine, tromethamine hydrochloride, and acetic acid as acid stabilizers can be substituted with citric acid monohydrate and trisodium citrate dihydrate, and vice versa. In other embodiments sodium acetate as a salt component can be substituted with potassium chloride, monobasic potassium phosphate, sodium chloride, and dibasic sodium phosphate dihydrate, and vice versa. Or either salt component may be substituted with sodium chloride, or vice versa. Persons of ordinary skill in the art with resort to this disclosure will realize other substitutions and combinations of ingredients that can be made.

[0077] In one embodiment the LNPs of the invention can contain a combination of 1,2- di-O-octadecenyl-3-trimethylammonium-propane (DOTMA) and 1,2-dioleoyl-sn-glycero-3- phosphoethanolamine (DOPE). In another embodiment the LNPs of the invention can contain a combination of 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) and DOPE and / or cholesterol.

[0078] In any of the embodiments disclosed herein, the LNPs can further contain other lipid components such as (but not limited to) phospholipids such as phosphatidylcholine and / or phosphatidylethanolamine.

[0079] LNPs and methods of their preparation are known to persons of ordinary skill in the art. LNPs can also be prepared using commercially available kits. In one embodiment the process of preparation can involve a step of mixing an ethanolic lipid mixture with an acidic aqueous buffer containing nucleic acids (e.g. an RNA molecule disclosed herein). In one embodiment a 1:3 ratio of ethanolic lipid mixture to aqueous buffer can be utilized.

[0080] In some embodiments the RNA molecules can be formulated within lipid nanoparticles (LNPs) prepared using the microfluidic technique. Ionizable cationic lipid, 1,2- distearoyl-sn-glycero-3-phosphocholine (DSPC), cholesterol, polyethylene glycol lipid PEG in ethanol are briefly combined with mRNA in pH 5.8 citrate buffer using a microfluidic mixer. The formulation can then be diluted and exchanged with 10 mM Tris (pH 7.0) containing series concentrations of sucrose. The formulation can be concentrated using ultra-centrifuge filters and passed through a 0.22 um filter, and then transferred into a vial and placed in a freeze-dryer for lyophilization, and then administration. Manufacturing and Biosafety Levels

[0081] The invention also provides more efficient methods of manufacturing BoNT of any serotype. The manufacture of BoNT is greatly complicated by its toxic nature, resulting in government requirements to produce it only in laboratories meeting safety requirements of a prescribed biosafety level for the particular toxin. The Food and Drug Administration (FDA) regulates the manufacture and distribution of botulinum toxin and other toxins. Botox® (Allergan, Inc., Irvine, CA) and other compositions are licensed under section 351 of the Public Health Service act pertaining to biological products (42 U.S.C.262). The FDA must approve the drug making process from the seed stock through the toxin production (from fermenters to purification, formulation, packaging, and labeling) to the final packaged product, under applicable laws and regulations.

[0082] In order to ensure the safety of lab personnel and the environment the U.S. government and / or State governments issue regulations prescribing biosafety levels through the Centers for Disease Control and Prevention (CDC) or other organizations or government agencies (or sub-agencies). The biosafety levels involve safety precautions for reducing a laboratory worker’s risk of exposure to a potentially harmful substance or microbe, and for protecting the work environment and community from accidental exposure or contamination. Each biosafety level corresponds to a level of specific safety precautions for a permitted facility. Requirements of a biosafety level can be “government prescribed” when there is a government issued regulation that imposes a penalty for failure to comply with the regulatory requirement. The penalty can be direct or indirect, direct meaning the penalty is imposed by a government actor (e.g. agency or sub-agency), and indirect meaning it is imposed by an actor other than a government agency or sub-agency (e.g. a University or educational institution), but which is otherwise under the control of a government agency or sub-agency with respect to biosafety requirements. In any embodiment the penalty can be imposition of a fine, imprisonment, or other loss of rights. Persons of ordinary skill in the art can easily discern the prescribed government biosafety level for a specific toxin, substance use, and jurisdiction. In various embodiments of the methods the government prescribed biosafety level can be BSL-1, or BSL-2, or BSL-3, or BSL-4. The biosafety level can also be Tier 1 or another sub-category of the prescribed levels. The biosafety levels can involve required structural characteristics of the facility and / or equipment requirements, and / or procedural requirements. While biosafety levels (BSLs) are widely known, the methods are also disclosed for government jurisdictions where the biosafety levels may be called by different names, but the requirements are the same or similar. Persons of ordinary skill in the art with resort to this disclosure will realize the corresponding biosafety level in such jurisdictions.

[0083] Each biosafety level carries with it requirements under which the work is performed, and those requirements too are easily discerned by persons of ordinary skill in the art. Depending on the type of work being performed botulinum toxin can be performed at a BSL-2 or BSL-3 level. The biosafety levels have general characteristics associated with them allowing them to be clearly identified. In various embodiments the government may be the U.S. government, but can also be a government outside the United States. The government or government agency can be any national government, the European Community (EC), the EC-funded European Network of Biosafety-Level-4 laboratories (Euronet-P4), the Japanese government, the Japanese Biological Safety Association (JBSA), or the World Health Organization (WHO). The general requirements of the biosafety levels are listed below: BSL-1

[0084] BSL-1 laboratories are required to follow the following protocols. The work can be performed on an open bench or table, and standard microbiological practices must be followed. The standard microbiological practices include: 1) mechanical pipetting (no mouth pipetting allowed); 2) Safe sharps handling, 3) Avoidance of splashes or aerosols, 4) Daily decontamination of all work surfaces when work is complete 5) Regular handwashing 6) Prohibition of food, drink, and smoking materials 7) The use of personal protective equipment (PPE) such as goggles, gloves, and a lab coat or gown, and 8) display of biohazard signs.

[0085] BSL-1 labs also require immediate decontamination after spills. Infectious materials should also be decontaminated prior to disposal, generally through the use of an autoclave. A sink must be available for hand washing, and the lab should have doors to separate the working space with the rest of the facility. BSL-2

[0086] BSL-2 laboratories are required to follow the protocols of BSL-1, plus the following protocols: 1) access to the laboratory is restricted when work with the regulated substance is being conducted; 2) PPE such as eye protection and face shields can be worn as needed;3) all procedures that can produce aerosols or splashes are performed within a biological safety cabinet compliant with BSL-2 requirements (e.g. air inflow for protecting the operator, an ULPA / HEA-filtered downflow, ULPA / HEPA-filtered exhaust); 4) an autoclave or an alternative method of decontamination is available for proper disposals; 5) the laboratory should have self-closing doors; 6) a sink and eyewash should be readily available. BSL-3

[0087] BSL-3 laboratories are required to follow the protocols of BSL-1 and BSL-2, plus the following: 1) Laboratory workers are under medical surveillance and might receive immunizations for microbes they work with. 2) Access to the laboratory is restricted and controlled at all times. 3) Appropriate PPE must be worn, and respirators may be required. 4) All work with microbes must be performed within an appropriate biosafety cabinet compliant with BSL-3 requirements (e.g. exhaust air is HEPA-filtered and incinerated, and materials are transferred into the cabinet using a pass-through unit, work is performed through glove ports, negative pressure relative to the ambient environment is maintained within the cabinet). 5) A hands-free sink and eyewash are available near the exit. 6) Exhaust air cannot be recirculated, and the laboratory must have sustained directional airflow by drawing air into the laboratory from clean areas towards potentially contaminated areas. 7) Entrance to the lab is through two sets of self-closing and locking doors. 8) Protective laboratory clothing with a solid front (e.g. tie back or wrap-around gowns, scrub suits, or coveralls must be worn.

[0088] The requirements of the biosafety levels are understood by persons of ordinary skill and are understood to have a level of certainty to them sufficient for implementation. Thelisted requirements may not be the only requirements, but simply a statement of some of the requirements and each BSL level can involve all possible combinations and sub-combinations of the listed requirements. In various embodiments the invention a BSL-2 laboratory can require any one or more, or at least two, or at least three, or at least four of the following requirements, disclosed here in all possible combinations and sub-combinations as if set forth fully: access to the laboratory is restricted when work is being conducted, all procedures that can produce aerosols or splashes are performed within a biological safety cabinet; an autoclave be available for proper disposals; the laboratory should have self-closing doors. In various embodiments a BSL-3 laboratory can require any one or more, or at least two, or at least three, or at least four of the BSL-2 components described above, plus any one or more, or at least two, or at least three, or at least four of the following, disclosed here in all possible combinations and sub-combinations as if set forth fully: that access to the laboratory is restricted and controlled at all times; that exhaust air not be recirculated, that the laboratory have sustained directional airflow (e.g. by drawing air into the laboratory from clean areas towards potentially contaminated areas); that the entrance to the laboratory is through two sets of self-closing and locking doors; that protective clothing be worn while working with hazardous materials that includes a solid front (e.g. tie back or wrap-around gowns, scrub suits, or coveralls). Similarly, the requirements of a BSL-2 or BSL-3 compliant laboratory equipment is also known to those of ordinary skill in the art.

[0089] Compliance with BSL2 and BSL-3 requirements can therefore be expensive, and the cost must be recouped by higher prices for the consumer or lower availability of the BoNT product. The invention therefore provides more efficient methods of synthesizing or producing BoNT, or other toxins. While the CDC prescribes BSL-2 or BSL-3 protocols for the synthesis of BoNT, the synthesis of only the light chain polypeptide of BoNT or only the heavy chain polypeptide of BoNT (or their corresponding encoding DNA or RNA sequences) is not regulated. Therefore, the invention allows for the cost of access to BSL-2 or BSL-3 compliant laboratories to be substantially reduced.

[0090] The Federal Select Agent Program (FSAP) regulates the possession, use, and transfer of biological select agents and toxins that have the potential to pose a severe threat to public health. The program is managed in part by the Division of Regulatory Science and Compliance (DRSC) at the Center for Disease Control and Prevention (CDC), which is part ofthe U.S. Department of Health and Human Services (HHS). The FSAP provides guidance and oversight regarding the creation or use of nucleic acids that encode for the toxic form(s) of any select toxins if the nucleic acids: (i) can be expressed in vivo or in vitro, or (ii) are in a vector or recombinant host genome and can be expressed in vivo or in vitro, including complete genomes as well as recombinant and / or synthetic nucleic acids. Currently, only nucleic acids that encode for the toxic forms of botulinum neurotoxins are regulated as Tier 1 agents by FSAP. However, DNA or RNA molecules encoding the light chain alone or the heavy chain alone are not regulated and are not classified as Tier 1 agents as they do not encode for the toxic form of the toxin. The heavy chain polypeptide alone is not toxic, and the light chain polypeptide alone is unable to enter a cell and is also not toxic by itself.

[0091] In some embodiments the invention involves synthesizing the light chain (LC) polypeptide of BoNT in a first laboratory facility that does not comply with or meet the requirements of a government prescribed biosafety level for the toxic polypeptide (e.g. BSL-2 or BSL-3), and synthesizing the heavy chain (HC) polypeptide of BoNT in a second laboratory facility that does not comply with or meet the requirements of a government prescribed biosafety level for the toxic polypeptide (e.g. BSL-2 or BSL-3). In one embodiment the laboratories can be separated laboratories within the same lab facility, or can be located at completely different laboratory facilities, such as a first facility and a second facility. The synthesized LC and HC polypeptides can then be brought together inside of a laboratory complying with or meeting the government prescribed biosafety level (e.g. BSL-2 or BSL-3) to thereby synthesize the toxic regulated polypeptide in accordance with all applicable government biosafety regulations. In any embodiment the toxic polypeptide can be botulinum toxin (BoNT). In any embodiment the light chain of BoNT / A can comprise a polypeptide sequence of any one or more of SEQ ID NOs: 29-56 or a variant of any. In any embodiment the heavy chain of BoNT / A can comprise a polypeptide sequence of any one or more of SEQ ID NO: 57-88 or a variant of any. The BoNT can also be the sequences of BoNT serotype B, C, D, E, F, or G. The government prescribed biosafety level will depend on the specific toxic polypeptide being used, and the work being done with it. It may also depend on the specific jurisdiction in which the work is occurring.

[0092] The methods of the invention therefore provide an mRNA approach to achieving the benefits of administration of botulinum toxin and other toxic polypeptides. In general, themethods can involve a step of extracting light chain (LC) polypeptide sequences, converting the polypeptide sequences to nucleic acid sequences optimized for human expression, building DNA templates, and expressing the mRNA and formulating the mRNA with lipid nanoparticles (LNPs). Example 1

[0093] This example illustrates methods for identifying light chain and heavy chain polypeptide sequences for BoNT / A and producing the holotoxin and confirming activity.

[0094] Twenty-eight non-redundant polypeptide sequences for eight different BoNT / A subtypes from Strain Hall, ATCC 3502 (which is representative of the Group I (proteolytic) botulinum producing bacteria) producing type A1 neurotoxin were identified using public databases (e.g. Uniprot). Strain Hall of Clostridium botulinum produces serotype A1 neurotoxin. The polypeptide light chain and heavy chain sequences were identified as SEQ ID NOs: 29-84. A pairwise comparison of the light chain polypeptides (SEQ ID NOs: 29-56) identified the percent identity existing between any two sequences. The light chains (LCs) were found to comprise amino acids 1-438, ending in K residues. A similar analysis was done for the heavy chains (HCs) (SEQ ID NOs: 57-84) and the HC polypeptides were found to comprise amino acids 439-1296, beginning with TK residues.

[0095] The 28 polypeptide sequences for the LCs and HCs are converted to DNA sequences and optimized for expression in E. coli using an online codon optimization tool. The DNA molecules are expressed and the polypeptides purified using steps of fermentation, homogenization, ammonium sulfate precipitation, and liquid chromatography. The LCs and HCs are brought to a laboratory compliant with BSL-2 or BSL-3 requirements, and within the compliant laboratory equal parts of the LCs and HCs are combined, passed through diafiltration, and then disfulfide bond (S-S) formation is performed to synthesize the final holotoxin, and the holotoxin stored. An SDS-PAGE gel is utilized to confirm the presence and separation of the LC and HC polypeptides.

[0096] To confirm activity SNAP-25 cleavage activity is verified for the LC polypeptide and the LC polypeptide screened for optimal kinetics using Kcat, Km, Vmax, and Kcat / Kmratios. A BoTest® botulinum neurotoxin detection kit (BioSentinel Pharmaceuticals, Madison, WI) is used following the manufacturer's instructions. Ten-fold serial dilutions of the BoNT / A subtypes are prepared in triplicate, and a negative control without BoNT added is included. All toxin samples are reduced prior to sensor addition by adding 100 mM DTT into the reaction buffer. The 96-well plate is incubated for up to 18 h at 30°C. Fluorescence emissions are measured on a microplate reader. The absorbance ratio of 470 nm / 526 nm is determined, and the EC50 (the concentration that produces 50% of the maximal possible effect) is estimated by nonlinear regression. The data is shown in Figure 1. Example 2 – Cell based assays

[0097] Cell-based assays for assessing and characterizing BoNT / A holotoxin activity are also utilized using human neurons. Human induced pluripotent stem cells (iPSC)-derived neurons are exposed to dilutions of BoNT / A and cell lysates analyzed for SNAP-25 cleavage by western blotting. Data from three western blots is quantified by densitometry and data plots, and EC50 values are generated using commercially available software, and the result shown in Figure 2. Log U / well on the x-axis is the logarithm of EC50, or the amount required to kill 50% of mice within 4 days after intraperitoneal injection.

[0098] Additional cell-based assays are performed with cultured mouse spinal cord (MSC) cells, primary rat spinal cord (RSC) cells, iCell neurons, and HIP neurons are exposed to similar concentrations of BoNT / A for 48 h, followed by removal of all extracellular toxin and thorough washing of the cells. Cells are lysed in 1x lithium dodecyl sulfate sample buffer and analyzed by western immunoblotting for SNAP-25 cleavage. Cleaved and uncleaved SNAP-25 bands are quantified by densitometry and data plots generated using commercially available software with a result shown in Figure 3, which shows that 100% cleavage of SNAP-25 is reached in all cell types. Example 3

[0099] This example illustrates methods for identifying and synthesizing mRNA encoding the light chain only of botulinum toxin, and formulating it into a pharmaceutical composition for administration to a patient.

[0100] The methods generally involve steps of extracting the light chain polypeptide sequences, converting the polypeptide sequences to DNA sequences, building DNA templates, expressing the mRNA and formulating the light chain mRNA with lipid nanoparticles for administration as a pharmaceutical composition.

[0101] The identification of 28 non-redundant polypeptide sequences for 8 different BoNT / A subtypes of the light chain of botulinum toxin in Clostridium botulinum (SEQ ID NOs: 29-56) is described above. The sequences are then optimized for expression in humans using an online codon optimization tool and synthesized as DNA sequences and a T7 promoter, 5’ and 3’ UTRs, and a polyA tail are added for in vitro transcription. The human optimized DNA sequences are SEQ ID NOs: 1-28.

[0102] The mRNA is then expressed from the DNA sequences with modified 5’ and 3’ untranslated regions (UTRs) flanking the coding sequence. UTRs are selected from endogenously found proteins with long half-lives that lack active mRNA synthesis (e.g. alpha- and beta-globulins). The RNA is also given a poly-A tail of 120-150 nucleotides, and a 5’ cap using a commercially available capping product to slow degradation of the construct and enhance its translation into proteins within cells. Example 4

[0103] The RNA molecules are formulated within lipid nanoparticles (LNPs), which are prepared using the microfluidic technique. Ionizable cationic lipid, 1,2-distearoyl-sn-glycero-3- phosphocholine (DSPC), cholesterol, polyethylene glycol lipid PEG in ethanol are briefly combined with mRNA in pH 5.8 citrate buffer using a microfluidic mixer. The formulation is then diluted and exchanged with 10 mM Tris (pH 7.0) containing series concentrations of sucrose. The formulation is concentrated using ultra-centrifuge filters and passed through a 0.22 um filter, and then transferred into a vial and placed in a freeze-dryer for lyophilization. The composition is then ready for administration.

[0104] Activity is verified using an in vitro assay (by first generating the LC / A polypeptide in vivo). Cell-based assays and in vivo animal testing are also used. Since the mRNA is translated into polypeptide the same cell-based assays described above for theholotoxin can be employed only substituting the LNP-encapsulated light chain mRNA. The activity-verified formulation is administered intra-muscularly by needle-free injection (NFI) to 5- 7 week old rats, and an antigen-specific antibody measured from serum by ELISA to confirms delivery. Alternatively, administration is performed using injection with a standard 30-32 gauge needle, but smaller gauge needles are also available and can also be used (Mao S. et al., Nano Today, 2023 Feb;48:101730.). Example 5

[0105] This example demonstrates the transfection of mammalian Expi293F cells with plasmid DNA encoding an optimized sequence for light chain mRNA of BoTN.

[0106] Expi293F cells (3 x 10e6 cells / ml) were seeded into 125 ml shake flasks. The following day cells were reseeded into a 24-well deep well plate with a density of 3 x 10e6 cells / ml and a total volume of 2 ml / well. The cells were transfected in duplicate using a commercially available transfection kit per the manufacturer’s protocol (ExpiFectamine® 293 transfection kit, Life Technologies, Inc., Carlsbad, CA) with 2 ug of DNA per well carrying a DNA expression vector encoding for RNA that encodes the light chain botulinum toxin of Hall_A1 (SEQ ID NO: 124) or for GreenLantern (SEQ ID NO: 125). The following day enhancers were added. 24 hours post transfection samples were collected and the cells counted. Samples were collected at 48 hours and 72 hours for flow cytometry and Western blot analysis and the cell count taken.

[0107] For mRNA Expi293F cells (3 x 10e6 cells / ml) were seeded into 125 ml shake flasks. On the following day cells were reseeded into a 24-well deep well plate with a density of 3 x 10e6 cells / ml and a total volume of 2 ml / well. The cells were transfected in a lipid nanoparticle with a commercially available lipid nanoparticle based transfection technology (MessengerMAX®, Life Technologies, Inc., Carlsbad, CA) per manufacturer’s protocol with 2 ug mRNA per well of an RNA encoding for the light chain botulinum toxin (A1_Hall light chain of SEQ ID NO: 124). Samples were collected at 24 and 48 hours for flow cytometry and Western blot analysis and the cell count taken.

[0108] Another series of cells were transfected with an RNA expression vector encoding for the mGreenLantern polypeptide (SEQ ID NO: 119) for easy visualization in confirming the site of expression. Table 1, count in millions / % live cells pDNA 24 h 48 h 72 h No DNA Well 1 5.55 / 98.2 6.61 / 98.8 3.07 / 90.7 Well 2 5.3 / 99.2 6.84 / 98.2 3.73 / 92.2 Green Lantern Well 1 5.3 / 99 6.96.97.4 4.03 / 92.4 Well 2 5.12 / 98.5 5.48 / 97.5 3.81 / 89.7 LC_A1_Hall Well 1 4.78 / 96.5 5.46 / 97.8 3.61 / 90.2 Well 2 4.8 / 97.2 5.41 / 96 3.46 / 86.5 Table 2, MessengerMAX®, (6 ul) mRNA, count in millions / % live cells mRNA 24 h 48 h No RNA Well 1 6.8 / 99.3 8.1 / 97.3 Well 2 6.7 / 99.4 7.1 / 94.7 Green Lantern Well 1 5.5 / 99.3 7.3 / 91.0 Well 2 4.9 / 99.5 7.3 / 91.0 LC_A1_Hall Well 1 4.0 / 98.8 4.0 / 89.5 Well 2 4.3 / 97.9 3.2 / 79.8

[0109] Tables 1-2 show good cell growth for the LC-A1_Hall sequence and that the RNA had no serious adverse effects on the cells, whether high or low amounts of the lipid delivery vehicle were used.

[0110] Figure 4a accompanies the data from Table 1 and provides a graphical illustration at 24h, 48h, and 72h showing that transfection of the pDNA did not substantially harm the Expi293F cells, also showing good viability at three time points. Figure 4b accompanies Table 2 and shows the cell count and % viability, respectively, for mRNA transfected cells at 24h and 48h, also demonstrating that transfection of the RNA did not substantially harm the cells. Thelow and high amounts refer to MessengerMAX® (3 ul and 6 ul, respectively (Life Technologies, Inc., Carlsbad, CA).

[0111] Flow cytometry data (Figures 5a-b) demonstrate that transcription of the plasmid DNA into RNA occurred. Figure 5a shows pDNA transfection in Expi293F cells at 24h, 48h, and 72h. The plasmid was introduced into the cells. Figure 5b shows the same for mRNA transfected cells at low and high amounts (3 ul or 6 ul) of MessengerMAX® (Life Technologies, Inc., Carlsbad, CA), illustrated transfection with both low and high amounts of the lipid vehicle at 24h and 48h.

[0112] Western blot data (Figure 6a-c) demonstrated translation of the mRNA into the light chain polypeptide in the cells, showing a Western blot of pDNA transfected cells at 24h. The LC_A1_Hall band is clearly visible, showing that translation of the mRNA occurred. The lanes were M: marker lane; Lane 1: 2 ng rBoNT-LC_A1_Hall; Lane 2: 5 ng rBoNT- LC_A1_Hall; Lanes 3-4: No DNA (controls); Lanes 5-6: mGreenLantern (10 ug); Lanes 7-8: LC_A- Hall (10 ug). rBoNT-LC is a commercially available control protein and LC_A1_Hall refers to intracellular expression of the light chain. Example 6

[0113] This example presents additional serotypes of the light chain of BoNT. Serotypes LC_A2 (SEQ ID NO: 122), LC_C (SEQ ID NO: 121), and LC_E (SEQ ID NO: 120) were coded into RNA expression vectors with LC_A1_Hall for comparison and transfected into Expi293F cells. Table 3, pDNA and MessengerMAX® count in millions / % live cells at 24h pDNA mRNA No DNA / RNA 4.8 / 98.0 4.6 / 96.6 Green Lantern 3.7 / 98.4 4.8 / 98.0 LC_A1_Hall 4.2 / 97.2 4.2 / 98.6 LC_A2 5.4 / 97.1 3.6 / 97.8LC_C 4.1 / 94.4 5.2 / 97.0 LC_E 4.2 / 96.3 5.9 / 99.0

[0114] The data show that the additional serotypes also were well expressed in the cells and also that the RNA had no serious adverse effects on the cells. These data are illustrated in Figures 7a-b. Flow cytometry analysis confirmed that pDNA and mRNA expression was occurring in the cells (data not shown). Western blot data showed that the LC_A, LC_C and LC_E polypeptides were all being expressed (Figures 8a-b). A negative control mutant was also expressed that was catalytically inactive. Figure 8c showing the amounts of each LC variant expressed from mRNA or pDNA controls, thus showing the variety of serotypes that can be successfully expressed. Example 7

[0115] This example shows mRNA-derived BoNT / C light chain exhibited specific proteolytic activity on a syntaxin peptide substrate.

[0116] Fluorescence-based BoNT / C activity assays were performed using the SYNTAXtide® (o-Abz / Dnp) (List Biological Laboratories, Inc., San Diego, CA) peptide substrate (which mimics the cleavage site on syntaxin). The test peptide contains an o-Abz fluorophore and a Dnp quencher. In this assay, an increase in fluorescence corresponds to peptide cleavage by the synthesized BoNT / C light chain. Each 250 µL reaction contained 10 µM substrate in assay buffer (20 mM HEPES, pH 6.8, 0.05% Tween-20).

[0117] Purified BoNT / C light chains were derived from either plasmid DNA or mRNA based expression in HEK cells (pDNA-LC_C and mRNA-LC_C (SEQ ID NO: 115), respectively) and were tested at 15, 75, and 125 ng / reaction. Commercially sourced BoNT / C light chain was included at the same concentrations as a positive control (Std-125). A “no BoNT” negative control was included as a baseline for assessing temperature-based fluorescence fluctuations and baseline drift. Reactions were incubated at 30°C and monitored in real time on a microplate reader that measured fluorescence using excitation at 320 nm and emission at 420 nm.

[0118] Figure 9a shows that mRNA-derived BoNT / C light chain exhibited specific proteolytic activity on a syntaxin-mimic peptide substrate over time. The robust increases in fluorescence confirmed cleavage and the mRNA-derived BoNT / C light chain demonstrated clear enzymatic activity, and therefore its ability to fold and function correctly following expression in mammalian cells. Also shown in graphical form are time-dependent fluorescence values and background-corrected endpoint fluorescence at 360 minutes (Figure 9b). The data therefore show a concentration-dependent increase in substrate cleavage with increasing enzyme levels. Example 8

[0119] This example shows mRNA-derived BoNT / A1 and BoNT / A2 light chains exhibit specific proteolytic activity on SNAP-25 peptide substrate.

[0120] Fluorescence-based BoNT / A activity assays were performed using the BoTest® A / E Botulinum Neurotoxin Detection Kit (BioSentinel, Inc., Madison, WI), which employs a FRET-based peptide. In this assay, a decrease in the 526 / 470 emission ratio corresponds with peptide cleavage by the light chain. Each 100 µL reaction included a SNAP-25-based peptide substrate in assay buffer and was incubated at 30°C.

[0121] Purified BoNT / A1 light chains derived from either plasmid DNA or mRNA (SEQ ID NO: 118) expression in HEK cells (pDNA-A1, mRNA-A1) were tested at 50 ng per reaction. An enzymatically inactivated mutant of BoNT / A1 expressed via pDNA and mRNA (SEQ ID NO: 113) was included at 50 ng per reaction as negative controls for peptide cleavage (pDNA- A1-neg and mRNA-A1-neg, respectively) (Figure 10a). Recombinant BoNT / A light chain was included at 5 ng, 25 ng, and 50 ng per reaction as positive controls (Figure 10c). A “no BoNT” control was used to assess photobleaching and baseline drift. Fluorescence was measured kinetically on a microplate reader using excitation at 434 nm and emissions at 470 nm (donor) and 526 nm (acceptor).

[0122] Figures 10a-b show emission ratios over time for BoNT / A1 and BoNT / A2, and that all catalytically active light chain molecules, including those derived from mRNA, demonstrated clear substrate cleavage as evidenced by a robust decrease in emission ratio. The “no BoNT” and catalytically inactive controls did not display a decrease, confirming assayspecificity and validating the enzymatic activity of mRNA-expressed BoNT / A light chains in mammalian cells. Figure 10b shows a similar result for BoNT / A2 (pDNA-A2, mRNA-A1) tested at the same concentration and against the same controls as BoNT / A1. Figure 10c shows the background corrected endpoint emission ratio for each condition. Example 9

[0123] This example illustrates a method for producing microgram quantities of light chain encoding mRNA molecules. Digital sequences were first built into DNA (SEQ ID NO: 1- 28 and 126), then transcribed into mRNA using an automated liquid handler (SEQ ID NO: 85- 113). The protein sequences encoded by these mRNAs are listed as SEQ ID NO: 29-56 and 127. In vitro transcription (IVT) reactions were performed using the BioXp® De novo mRNA Synthesis Kit (Telesis Bio, Inc., San Diego, CA), which includes all necessary reagents to generate capped and polyadenylated mRNA directly from a digital DNA sequence. The workflow is fully automated on the BioXp® 3250 system (Telesis Bio Inc., San Diego, CA), beginning with synthesis of an error-corrected linear DNA template, followed by in vitro transcription using CleanCap® AG (3′OMe) (TriLink Biotechnologies, San Diego, CA) co- transcriptional capping and optional incorporation of N1-methyl-pseudouridine. The resulting mRNA included a 5′ cap and poly(A) tail and was delivered as a purified, single-stranded product. After mRNA was produced, the products were analyzed using Tapestation® (Agilent Technologies, Inc., Santa Clara, CA) to assess the purity and yield of the mRNAs. The sequences corresponding to each well were: Well Sample Name mRNA conc. mRNA yield DNA conc. UPI# ( / l) ( ) ( / l)D1 A100027EE164 46.5 32.55 158.2 SEQ ID NO: 88C1 A3000290C3D0 66.6 46.62 169.5 SEQ ID NO:103Example 10

[0124] This example illustrates another method for manufacturing lipid nanoparticles. Lipid nanoparticles are known in the art and persons of ordinary skill with resort to thisdisclosure will realize various methods of readily synthesizing LNP formulations. Lipids (e.g. phospholipids, cholesterol, and helper PEGylated lipids) are dissolved in an organic solvent such as ethanol. An aqueous phase is also prepared containing the payload RNA molecule (any disclosed herein) and an acidic pH facilitates encapsulation of the RNA.

[0125] Upon mixing the lipids self-assemble into nanoparticles. The ionizable lipids become protonated and bind to the RNA, thereby encapsulating it. The pH is adjusted to increase the stability of the LNP. LNPs are then purified by dialysis to remove residual ethanol and acidic buffers. The LNPs are assessed by size, charge, and encapsulation efficiency using dynamic light scattering and transmission electron microscopy.Sequence ListingSEQ ID NO: 1, DNA, artificial, light chain botulinum, human optimized from Hall Strain UPI0000001386TCGAGCTCGGTACCTAATACGACTCACTATAAGGAGGAAATAAGAGAGAAAAGAAGAGTAAGAAGAAATATAAGAGCCACCATGCCGTTTGTGAACAAACAATTCAACTATAAGGATCCCGTTAACGGAGTCGATATAGCCTACATCAAGATACCCAATGCGGGCCAAATGCAACCCGTGAAGGCATTTAAAATCCATAACAAGATATGGGTAATCCCGGAACGAGATACCTTCACCAATCCTGAAGAGGGGGATCTGAACCCGCCGCCAGAGGCCAAGCAAGTTCCGGTCTCATACTACGATAGCACATACCTCTCTACCGACAACGAAAAAGACAATTACTTGAAAGGGGTCACGAAGCTCTTCGAGAGAATATATAGCACGGATCTTGGCAGGATGCTTCTGACATCCATAGTGAGAGGTATACCGTTCTGGGGCGGATCAACAATAGACACGGAACTGAAAGTCATAGACACAAACTGTATCAACGTGATTCAGCCGGATGGAAGCTATCGCAGCGAAGAGTTGAACCTGGTGATAATTGGACCAAGCGCAGACATTATCCAATTTGAATGTAAATCATTTGGGCACGAAGTATTGAACCTCACAAGGAACGGGTATGGCTCAACACAGTATATCAGGTTCTCCCCAGACTTTACCTTTGGTTTCGAAGAGTCTCTGGAGGTGGATACCAACCCCTTGCTTGGTGCGGGAAAATTTGCTACAGACCCAGCTGTGACGCTGGCACACGAGCTGATCCATGCAGGCCACCGCCTTTATGGGATCGCGATCAACCCGAACCGGGTTTTCAAGGTCAACACTAATGCATATTACGAAATGTCTGGTCTTGAAGTCAGTTTCGAAGAGTTGCGGACCTTCGGTGGCCACGATGCCAAGTTCATTGATTCATTGCAAGAAAATGAATTTCGACTCTATTACTACAACAAATTTAAAGATATTGCAAGTACACTTAATAAGGCGAAGTCTATAGTGGGGACCACCGCGAGCCTGCAGTATATGAAGAATGTATTCAAGGAAAAGTATTTGCTCTCTGAAGACACGTCAGGGAAGTTTAGCGTAGATAAGCTGAAGTTTGATAAACTGTATAAGATGCTCACGGAGATTTATACGGAGGATAACTTCGTAAAATTCTTCAAGGTGCTGAACAGAAAAACTTACCTGAATTTTGATAAAGCCGTCTTTAAGATCAATATAGTGCCGAAGGTTAATTATACGATATACGATGGCTTTAATCTTCGCAATACTAATTTGGCTGCCAACTTTAACGGTCAGAACACCGAGATTAATAATATGAACTTTACTAAATTGAAGAACTTTACTGGCCTCTTTGAATTTTATAAGTTGCTGTGCGTAAGAGGTATAATCACCTCAAAATAAGCGGCCGCTTAATTAAGCTGCCTTCTGCGGGGCTTGCCTTCTGGCCATGCCCTTCTTCTCTCCCTTGCACCTGTACCTCTTGGTCTTTGAATAAAGCCTGAGTAGGAAGAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAASEQ ID NO: 2, DNA, artificial, light chain botulinum, human optimized from Strain UPI000559A469TCGAGCTCGGTACCTAATACGACTCACTATAAGGAGGAAATAAGAGAGAAAAGAAGAGTAAGAAGAAATATAAGAGCCACCATGCCATTCGTCAACAAACAGTTCAACTACAAGGATACTGTTAACGGGATCGACATCGCCTACATCAAAATACCTAATGCTGGTCAAATGCAGCCTGTTAAAGCATTCAAGATTCACAACAAAATCTGGGTTATCCCAGAAAGAGACACATTCACAAACCCTAAAGAAGGTGATCTTAATCCACCTCCTGAAGCGAAACAGGTACCCGTATCCTATTATGATTCTACCTACCTTTCTACGGATAACGAAAAAGATAACTACCTGAAGGGTGTCACTAAATTGTTTGAGCGAATCTATTCTACAGATCTTGGCCGAATGCTCTT GACGTCCATTGTACGAGGCATACCCTTTTGGGGCGGGTCTACCATAGACACAGAACTT AAGGTAATCGACACGAACTGCATTAATGTCATTCAACCCGATGGGTCCTATAGGTCTG AAGAATTGAATCTCGTGATCATCGGTCCCAGCGCAGATATCATACAGTTTGAATGCAA AAGTTTTGGACACGATGTCCTGAATTTGACGCGCAATGGCTATGGTAGCACTCAGTAT ATCCGCTTTAGCCCTGATTTTACTTTCGGCTTTGAGGAATCATTGGAAGTAGACACTAA TCCCCTGCTCGGAGCGGGGAAGTTTGCGACAGATCCTGCCGTAACCCTGGCGCATGA GCTGATACATGCAGAACATCGCCTGTACGGAATTGCCATAAATCCTAATCGAGTCTTC AAGGTAAATACAAATGCCTACTACGAGATGTCTGGGTTGGAGGTCTCTTTCGAGGAAT TGCGGACCTTCGGTGGCCACAACGCCAAATTTATCGACTCATTGCAAGAGAATGAATT TCGGCTCTATTATTACAATAAATTTAAGGACATTGCTTCTACACTTAATAAAGCTAAAA GCATTGTAGGAACTACAGCATCCCTTCAGTATATGAAAAATGTCTTCAAGGAAAAGTACCTGCTCTCAGAGGATACCTCCGGGAAGTTTTCTGTTGATAAACTCAAGTTTGACAAA CTCTATAAGATGTTGACTGAGATTTATACCGAGGATAACTTCGTGAAATTTTTTAAAGT ATTGAATAGAAAGACGTATCTTAACTTTGACAAAGCTGTGTTTAAGATAAATATCGTAC CAGACGAAAATTACACGATCAAGGACGGGTTCAATTTGAAAAACACAAACCTCGCCG CCAACTTTAACGGGCAAAACACGGAAATCAACTCTCGCAATTTTACAAAACTGAAGA ATTTCACTGGCCTTTTTGAGTTTTACAAACTTTTGTGTGTGCGGGGCATAATACCGTTT AAGTGAGCGGCCGCTTAATTAAGCTGCCTTCTGCGGGGCTTGCCTTCTGGCCATGCCC TTCTTCTCTCCCTTGCACCTGTACCTCTTGGTCTTTGAATAAAGCCTGAGTAGGAAGAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA AAAAAAAAAAAAAAAAAAAAAAAAASEQ ID NO: 3, DNA, artificial, light chain botulinum, human optimized from Strain UPI0003C9D2A1TCGAGCTCGGTACCTAATACGACTCACTATAAGGAGGAAATAAGAGAGAAAAGAAGA GTAAGAAGAAATATAAGAGCCACCATGCCATTTGTCAACAAGCAATTCAACTACAAG GATACTGTGAACGGTGTCGACATTGCCTACATCAAGATACCCAATGCTGGACAAATGC AACCTGTCAAAGCCTTCAAAATACATAATAAGATCTGGGTCATCCCGGAAAGAGACA CGTTTACCAATCCAAAGGAGGGAGACCTGAACCCGCCTCCCGAGGCAAAACAGGTA CCGGTTTCTTACTATGATAGCACCTATCTGTCTACCGATAACGAGAAGGATAACTATCT TAAAGGTGTGACAAAACTCTTTGAACGAATATATTCCACAGACCTGGGACGGATGCTC CTTACTAGCATTGTGCGCGGCATTCCATTCTGGGGGGGCTCTACAATCGACACTGAACTTAAGGTAATTGACACGAACTGCATAAATGTGATACAACCTGATGGGTCCTATAGGAG TGAAGAACTTAACTTGGTAATCATAGGTCCCAGTGCCGATATTATTCAGTTCGAGTGTA AAAGCTTCGGACACGATGTGTTGAACCTGACGAGGAATGGTTATGGCTCCACACAGT ATATTCGCTTCTCTCCAGACTTTACCTTCGGTTTTGAGGAGTCATTGGAAGTCGACAC TAATCCTCTGCTGGGGGCGGGTAAGTTCGCGACCGACCCGGCGGTCACTCTTGCACA TGAACTCATACATGCAGAGCACCGGCTGTATGGCATAGCGATCAATCCAAACAGGGTT TTTAAAGTAAATACAAACGCGTATTACGAAATGAGCGGTCTCGAAGTTAGCTTCGAAG AACTGAGGACATTTGGAGGACATAACGCCAAATTCATCGACTCCTTGCAGGAAAATG AGTTTCGCCTCTACTATTATAATAAGTTTAAGGACATAGCTTCAACTCTCAATAAGGCT AAGAGCATTGTCGGGACCACAGCAAGTCTCCAATACATGAAAAATGTGTTCAAAGAAAAATACTTGCTTTCCGAGGATACATCAGGAAAATTTAGCGTGGACAAGCTGAAGTTCG ATAAGCTCTACAAAATGCTGACGGAGATCTATACTGAAGATAATTTTGTGAAATTCTTC AAGGTACTTAATAGAAAGACTTATCTCAATTTCGATAAAGCGGTGTTTAAGATCAATAT CGTGCCTGATGAGAACTATACCATCAAGGATGGATTCAATCTTAAGAATACTAATCTTG CAGCCAACTTTAACGGGCAAAATACGGAAATCAACAGTAGGAACTTCACGAAGTTGA AGAACTTCACTGGACTTTTCGAGTTTTACAAATTGCTTTGCGTGCGAGGTATAATACC CTTCAAGTGAGCGGCCGCTTAATTAAGCTGCCTTCTGCGGGGCTTGCCTTCTGGCCAT GCCCTTCTTCTCTCCCTTGCACCTGTACCTCTTGGTCTTTGAATAAAGCCTGAGTAGG AAGAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAASEQ ID NO: 4, DNA, artificial, light chain botulinum, human optimized from Strain UPI000290B995TCGAGCTCGGTACCTAATACGACTCACTATAAGGAGGAAATAAGAGAGAAAAGAAGAGTAAGAAGAAATATAAGAGCCACCATGCCTTTTGTGAACAAGCAGTTTAATTATAAAG ATCCCGTGAACGGAGTTGACATAGCCTACATTAAAATTCCCAACGCAGGGCAAATGC AGCCGGTAAAAGCCTTCAAGATTCACAATAAGATTTGGGTCATTCCCGAACGGGACA TATTCACAAATCCCGAAGAAGGAGATCTGAATCCACCACCGGAGGCAAAACAAGTTCCCGTAAGTTACTACGACAGCACTTATTTGAGTACGGACAATGAGAAGGACAATTACTT GAAAGGCGTAACGAAGCTCTTCGAGCGCATTTATTCCACAGACTTGGGGCGCATGCT GCTCACCAGCATCGTACGGGGCATTCCATTTTGGGGTGGGTCAACGATTGATACGGAG TTGAAAGTAATTGATACAAATTGTATTAACGTCATTCAGCCGGATGGTTCTTATAGAAGTGAGGAGCTTAATCTTGTGATTATCGGGCCTTCTGCAGATATAATAAACTTCGAATGCAAATCCTTCGGGCACGACGTGCTCAACCTGACGCGGAATGGGTATGGTTCTACGCAGTATATACGATTCAGTCCCGATTTTACCTTTGGCTTCGAGGAAAGTTTGGAAGTCGATAC GAACCCGCTTCTCGGCGCGGGTAAATTCGCAATAGACCCAGCCGTGACCTTGGCGCA CGAACTCATTCACGCAGGTCATCGGTTGTATGGCATTGCAATAAACCCCAATAGAGTC TTCAAGGTGAATACTAACGCGTATTATGAGATGTCAGGTTTGGAGGTGTCTTTTGAAGAGTTGAGGACATTCGGCGGTCACGACGCTAAATTTATCGATTCCTTGCAGGAGAACGAATTTCGCCTTTACTACTATAACAAGTTTAAGGAAGTCGCTAGCATACTTAACAAAGCGAAATCAATCATTGGAACCACAGCATCATTGCAGTACATGAAGAATGTGTTCAAAGAAAAGTACCTTCTTTCTGAGGATACCTCTGGTAAATTCTCAGTCGATAAACTCAGGTTC GATAAGCTTTACAAGATGTTGACCGAGATTTATACCGAAGACAACTTTGTCAAGTTTT TTAAGGTACTTAATCGCAAAACATACTTGAATTTTGACAAAGCCGTGTTTAAGATGAA CATTGTACCGGAGGTTAATTATACAATCTACGATGGATTCAACCTCCGAAATACAAACTTGGCAGCCAACTTCAACGGTCAGAACACAGAGATAAACAACATGAATTTTACTAAACTGAAAAATTTCACCGGTCTTTTTGAGTTCTACAAGCTCCTGTGCGTTCGAGGAATTAT CACGAGTAAATAGGCGGCCGCTTAATTAAGCTGCCTTCTGCGGGGCTTGCCTTCTGGC CATGCCCTTCTTCTCTCCCTTGCACCTGTACCTCTTGGTCTTTGAATAAAGCCTGAGTA GGAAGAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAASEQ ID NO: 5, DNA, artificial, light chain botulinum, human optimized from Strain UPI0001B7D251TCGAGCTCGGTACCTAATACGACTCACTATAAGGAGGAAATAAGAGAGAAAAGAAGAGTAAGAAGAAATATAAGAGCCACCATGCCCTTTGTAAATAAGCAGTTCAATTATAAAGACCCGGTAAACGGGGTGGACATTGCGTACATTAAGATTCCCAACGCGGGGCAAATGC AGCCGGTCAAAGCCTTTAAAATACATAACAAGATCTGGGTCATACCTGAACGGGATAC TTTTACAAATCCCGAGGAAGGTGACTTGAATCCCCCACCAGAGGCAAAGCAAGTACC GGTCAGCTACTACGACTCCACCTATTTGAGTACGGACAACGAAAAGGATAATTATCTCAAAGGAGTAACAAAGCTGTTCGAACGGATTTATTCAACTGATTTGGGACGGATGCTTCTTACTTCCATAGTCCGGGGTATTCCGTTTTGGGGAGGTTCCACTATCGACACAGAACTCAAGGTGATTGATACAAATTGCATCAACGTTATTCAACCAGATGGCTCATACCGGTCAGAAGAGTTGAACCTTGTGATAATCGGACCCTCAGCTGATATAATACAATTTGAATGTAAGTCCTTCGGGCATGAGGTTCTTAATCTGACCCGAAATGGTTATGGTAGTACTCAAT ATATTAGGTTTAGTCCCGATTTCACATTTGGGTTCGAGGAATCACTGGAGGTAGATACT AACCCCCTGCTGGGCGCTGGCAAATTCGCCACGGACCCCGCGGTGACCCTGGCACAC GAGCTGATACACGCGGGCCATCGACTGTACGGTATTGCCATCAATCCGAATAGGGTGTTTAAAGTGAATACCAACGCGTATTACGAAATGTCAGGTTTGGAAGTCTCTTTCGAGGAGCTTAGAACATTCGGGGGACATGATGCGAAGTTCATTGATAGTCTTCAAGAGAACGAATTTAGACTCTATTACTACAACAAATTTAAAGATATTGCTTCAACCCTCAATAAGGCGA AGTCAATAGTGGGGACCACAGCCAGCCTGCAATACATGAAGAATGTCTTCAAGGAGA AGTATCTCCTCTCAGAGGACACTTCAGGTAAGTTTAGCGTCGACAAGCTTAAATTTGA TAAACTTTACAAGATGCTTACTGAAATTTATACAGAAGATAACTTCGTCAAATTCTTCAAAGTCCTCAATAGGAAAACATATTTGAATTTTGATAAGGCCGTTTTTAAGATCAACATTGTACCAAAAGTGAACTACACAATATATGACGGTTTTAATCTTCGAAACACCAATCTTGCAGCTAACTTTAATGGGCAAAACACTGAGATTAATAACATGAATTTCGCTAAACTCAAAAATTTCACTGGTCTCTTTGAGTTTTATAAGCTCTTGTGCGTCAGGGGCATTATAACCTCTAAGTAAGCGGCCGCTTAATTAAGCTGCCTTCTGCGGGGCTTGCCTTCTGGCCATGCCCTTCTTCTCTCCCTTGCACCTGTACCTCTTGGTCTTTGAATAAAGCCTGAGTAGGAA GAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA AAAAAAAAAAAAAAAAAAAAAAAAAAASEQ ID NO: 6, DNA, artificial, light chain botulinum, human optimized from Strain UPI0001AE7D6ATCGAGCTCGGTACCTAATACGACTCACTATAAGGAGGAAATAAGAGAGAAAAGAAGAGTAAGAAGAAATATAAGAGCCACCATGCCCTTTGTGAACAAACAGTTCAACTATAAG GACCCAGTAAACGGGGTGGACATCGCTTACATCAAGATTCCAAATGCGGGGCAAATG CAGCCCGTAAAAGCCTTCAAGATTCACAACAAAATCTGGGTTATTCCCGAAAGAGAT ACTTTCACAAATCCTGAAGAAGGTGACTTGAACCCACCACCAGAAGCGAAGCAAGTGCCAGTAAGCTATTATGATAGTACATATTTGAGCACAGACAATGAAAAGGACAATTAC CTCAAAGGCGTTACAAAACTGTTTGAGCGGATATATAGCACTGAGCTCGGCCGGATGC TCCTGACTTCCATCGTCAGAGGCATCCCGTTTTGGGGCGGCAGTACCATCGATACAGA ATTGAAAGTAATAGATACGAATTGTATAAATGTCATACAACCAGACGGAAGTTATAGATCCGAGGAACTGAATCTGGTAATAATTGGACCTTCCGCGGATATAATACAATTCGAATGCAAGTCCTTCGGACACGATGTGCTGAACCTTACAAGGAATGGATACGGGAGTACGCAG TATATCAGGTTCTCTCCTGATTTCACCTTTGGGTTTGAGGAGAGCCTGGAAGTTGACA CGAACCCCCTTCTGGGGGCCGGCAAATTTGCAACGGACCCGGCCGTAACACTTGCGC ATGAATTGATCCACGCCGGTCATAGACTTTACGGAATCGCCATTAATCCGAATAGAGTGTTTAAGGTGAATACGAACGCGTATTACGAGATGTCAGGACTGGAAGTTAGCTTCGA GGAACTCCGCACGTTCGGAGAGCATGATGCAAAATTCATCGACTCACTGCAAGAAAA TGAGTTTAGGCTGTATTATTACAATAAGTTCAAGGATATAGCATCTACATTGAACAAAG CGAAATCAATAGTAGGCACCACCGCTTCTTTGCAATACATGAAGAATGTCTTCAAGGAAAAGTATTTGCTGTCTGAAGATACCTCTGGGAAATTCAGTGTGGATAAGTTGAAGTTC GACAAATTGTACAAGATGCTGACCGAAATTTATACAGAAGACAACTTCGTAAAATTCT TCAAGGTCCTGAATCGCAAGACTTACCTGAACTTTGACAAGGCGGTCTTTAAGATAA ACATAGTCCCAGAAGTTAACTACACCATATACGATGGCTTCAACCTTAGGAATACGAACTTGGCGGCGAACTTTAATGGGCAAAATACGGAGATTAACAATATGAATTTTACTAAACTCAAGAACTTCACGGGGTTGTTTGAGTTTTACAAACTTCTGTGCGTCCGGGGTATTATAACTAGCAAATAAGCGGCCGCTTAATTAAGCTGCCTTCTGCGGGGCTTGCCTTCTGG CCATGCCCTTCTTCTCTCCCTTGCACCTGTACCTCTTGGTCTTTGAATAAAGCCTGAGT AGGAAGAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAASEQ ID NO: 7, DNA, artificial, light chain botulinum, human optimized from Strain UPI000198BDAETCGAGCTCGGTACCTAATACGACTCACTATAAGGAGGAAATAAGAGAGAAAAGAAGAGTAAGAAGAAATATAAGAGCCACCATGCTCTTTGTGAACAAACAATTCAATTATAAGGATCCTGTCAACGGTGTTGATATAGCCTACATCAAAATCCCGAACGCCGGGCAAATGCA ACCAGTAAAAGCGTTTAAGATACACAACAAAATCTGGGTGATCCCAGAGAGGGACAC CTTTACAAATCCTGAGGAGGGTGATCTGAATCCACCTCCTGAAGCTAAACAAGTACC AGTTTCATATTACGATAGCACATATTTGAGCACCGACAATGAGAAAGATAACTACTTGAAGGGAGTAACTAAACTCTTTGAACGCATTTATTCAACCGAGTTGGGGAGGATGCTG CTTACCAGTATAGTGCGGGGCATTCCGTTTTGGGGCGGCTCTACGATAGACACTGAGC TGAAAGTAATTGATACCAATTGCATCAACGTGATTCAGCCGGACGGATCTTACAGGTC AGAGGAACTTAATCTTGTGATTATTGGCCCCTCTGCCGATATCATACAGTTTGAATGCAAATCCTTCGGTCACGATGTCTTGAACCTGACCCGGAACGGCTATGGCTCTACCCAATA TATTCGGTTCAGCCCCGATTTTACTTTCGGTTTTGAGGAAAGTCTCGAGGTGGATACA AACCCTCTCCTCGGGGCCGGGAAATTCGCCACCGACCCGGCGGTGACGCTCGCCCAT GAACTTATACATGCTGGCCACCGCCTTTATGGGATTGCCATAAATCCGAACAGAGTGTTTAAGGTCAATACGAATGCCTATTATGAAATGAGTGGCCTCGAGGTTTCTTTCGAAGAACTCCGGACATTTGGAGAGCATGATGCTAAGTTCATAGATTCCCTCCAAGAGAACGA GTTTAGGCTCTACTACTACAATAAATTCAAAGACATCGCTTCCACCCTTAACAAAGCG AAGTCCATCGTGGGAACGACAGCAAGCCTTCAGTACATGAAAAACGTATTTAAAGAG AAGTACCTCCTTTCTGAGGACACGTCAGGGAAATTCTCCGTCGATAAATTGAAATTCGACAAGTTGTATAAAATGCTGACAGAAATATACACAGAAGACAATTTCGTCAAATTCTT TAAAGTCCTGAATAGAAAAACATATCTGAATTTCGATAAGGCTGTTTTCAAAATAAATATCGTCCCGGAGGTGAATTACACCATTTACGACGGATTTAACCTCAGGAATACCAATTTGGCCGCTAACTTCAACGGGCAGAACACAGAGATAAACAATATGAACTTCACCAAGCTGAAGAATTTCACGGGCCTTTTCGAGTTTTATAAACTTCTTTGCGTCCGAGGTATCATTACTTCCAAGTAGGCGGCCGCTTAATTAAGCTGCCTTCTGCGGGGCTTGCCTTCTGGCCATGCCCTTCTTCTCTCCCTTGCACCTGTACCTCTTGGTCTTTGAATAAAGCCTGAGTAGG AAGAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA AAAAAAAAAAAAAAAAAAAAAAAAAAAAASEQ ID NO: 8, DNA, artificial, light chain botulinum, human optimized from Strain UPI00019DB885TCGAGCTCGGTACCTAATACGACTCACTATAAGGAGGAAATAAGAGAGAAAAGAAGAGTAAGAAGAAATATAAGAGCCACCATGCCATTCGTCAACAAACAATTTAACTACAATGATCCAGAAAACGGGGTAGACATTGCATACATTAAGATACCTAACGCTGGCAAGATGCAGCCCGTGAAAGCTTTCAAGATACATAACAAAGTATGGGTGATCCCCGAAAGAGACATCTTTACAAATCCTGAGGAGGTGGACCTGAATCCTCCACCAGAAGCCAAACAGGTACCCATATCCTACTACGACAGCGCCTACCTCTCAACCGACAACGAAAAAGATAATTATCTTAAAGGCGTGATAAAACTCTTTGAAAGGATATATTCCACGGACCTTGGAAGAATGCTGCTCATCAGCATCGTACGCGGCATCCCGTTTTGGGGTGGAGGCAAGATCGACACTGAGCTGAAAGTTATTGATACTAACTGCATCAACATTATTCAACTGGATGACTCATATCGATCCGAGGAACTGAATCTGGCTATAATTGGCCCTAGTGCGAATATAATTGAGTCTCAATGCTCATCTTTCCGAGATGATGTCCTCAATTTGACCCGAAATGGCTACGGCTCCACTCAATACATCCGCTTTTCCCCAGACTTCACTGTAGGTTTCGAAGAATCCCTCGAAGTAGATACAAACCCGCTGCTGGGTGCCGGGAAGTTTGCGCAAGACCCAGCAGTTGCGCTTGCACACGAGCTCATCCATGCTGAACACAGGCTGTACGGGATCGCTATCAACACGAATAGAGTCTTTAAGGTGAACACTAATGCCTATTATGAGATGGCTGGACTCGAAGTAAGCCTTGAGGAACTCATAACGTTCGGGGGCAATGACGCAAAGTTTATAGATTCTTTGCAAAAAAAGGAATTTTCCCTTTACTACTATAACAAGTTTAAGGACATCGCGTCCACTCTGAACAAGGCGAAATCCATCGTAGGCACTACAGCTTCACTTCAATATATGAAGAACGTCTTCAAAGAGAAATACTTGCTTAGTGAAGACGCCACGGGGAAGTTCCTCGTTGACCGGCTCAAGTTTG ATGAAC TTTATAAGC TC CTTAC TGAAATCTATAC GGAGGATAATTTTGTC AAATTTTTTA AAGTACTCAATCGCAAAACTTATCTCAATTTTGACAAGGCGGTTTTTAAAATAAACATTGTACCTGATGTGAACTATACGATACACGATGGGTTTAATCTTCGCAACACAAACCTTGCGGCAAACTTCAATGGGCAGAATATTGAAATCAACAATAAGAATTTTGATAAGCTGAAGAACTTTACTGGCTTGTTCGAATTCTACAAGCTCCTGTGTGTTCGGGGTATTATCACCTCTAAATAGGCGGCCGCTTAATTAAGCTGCCTTCTGCGGGGCTTGCCTTCTGGCCATGCCCTTCTTCTCTCCCTTGCACCTGTACCTCTTGGTCTTTGAATAAAGCCTGAGTAGGA AGAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA AAAAAAAAAAAAAAAAAAAAAAAAAAAASEQ ID NO: 9, DNA, artificial, light chain botulinum, human optimized from StrainUPI00005B712DTCGAGCTCGGTACCTAATACGACTCACTATAAGGAGGAAATAAGAGAGAAAAGAAGA GTAAGAAGAAATATAAGAGCCACCATGCCCCTCGTGAATCAGCAAATTAACTACTACG ACCCGGTTAACGGCGTGGACATTGCTTATATAAAGATACCTAACGCTGGGAAGATGCA ACCAGTTAAGGCGTTTAAAATCCACAATAAGGTATGGGTCATTCCCGAACGAGATATA TTTACTAACCCGGAGGAGGTAGATCTTAACCCGCCTCCAGAGGCTAAGCAAGTCCCG ATCTCCTATTACGATAGTGCCTACCTGTCCACCGACAATGAAAAGGACAACTACTTGA AGGGGGTGATCAAGCTGTTTGAGAGGATTTATAGCACTGACCTGGGGCGCATGTTGTT GATAAGCATAGTTAGAGGGATACCTTTTTGGGGCGGCGGTAAAATCGACACCGAGCTC AAAGTGATAGATACTAACTGCATTAACATTATCCAGCTGGATGATTCATACCGCTCTGA GGAACTGAACCTCGCGATTATTGGCCCAAGCGCGAACATTATAGAATCCCAGTGCTCC TCCTTTAGGGATGATGTTCTTAACTTGACCAGGAACGGATATGGTTCAACTCAATATAT AAGGTTTAGCCCAGACTTTACTGTAGGATTCGAGGAAAGTCTCGAGGTGGACACTAA CCCGCTGCTCGGTGCGGGAAAATTTGCACAAGACCCGGCTGTCGCTCTGGCTCATGA ACTCATCCATGCCGAACACCGCTTGTACGGTATTGCGATCAACACTAATCGAGTATTTA AGGTCAACACCAATGCCTACTACGAGATGGCTGGATTGGAGGTAAGCCTGGAAGAAT TGATTACATTTGGGGGGAACGATGCGAAATTTATAGACAGCTTGCAGAAGAAGGAGT TCAGTCTCTACTATTACAATAAATTTAAGGACATCGCAAGTACGCTGAACAAAGCTAA ATCTATAGTCGGAACTACAGCTAGTCTCCAATACATGAAGAATGTATTCAAGGAGAAA TATCTTCTGAGCGAAGATGCAACCGGTAAATTTCTCGTTGATCGGTTGAAGTTTGACG AACTCTATAAACTGCTGACAGAAATATATACCGAAGATAATTTCGTAAAATTCTTTAAA GTACTTAACCGCAAGACATATCTCAATTTTGACAAAGCTGTGTTTAAGATTAATATAGT GCCTGATGTTAACTATACGATACACGACGGCTTTAACCTCCGAAACACGAACCTGGCTGCAAACTTTAACGGACAAAATATTGAAATCAATAACAAAAACTTTGACAAGCTGAAA AACTTTACTGGACTGTTCGAATTTTACAAACTGCTTTGCGTCCGGGGCATAATTACGT CCAAATAGGCGGCCGCTTAATTAAGCTGCCTTCTGCGGGGCTTGCCTTCTGGCCATGC CCTTCTTCTCTCCCTTGCACCTGTACCTCTTGGTCTTTGAATAAAGCCTGAGTAGGAA GAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA AAAAAAAAAAAAAAAAAAAAAAAAAAASEQ ID NO: 10, DNA, artificial, light chain botulinum, human optimized from Strain UPI000290C3D0TCGAGCTCGGTACCTAATACGACTCACTATAAGGAGGAAATAAGAGAGAAAAGAAGA GTAAGAAGAAATATAAGAGCCACCATGCCATTTGTCAACAAACAATTCAACTATCGCG ATCCTGTGAATGGAGTGGATATAGCCTACATAAAGATTCCAAACGCCGGACAGATGCA ACCTGTAAAGGCCTTTAAAATCCACGAGGGAGTATGGGTTATCCCTGAACGCGATACC TTCACAAACCCAGAGGAAGGAGACTTGAACCCGCCTCCGGAAGCGAAGCAAGTGCC CGTCTCTTATTACGACTCAACATACTTGAGCACAGACAACGAGAAGGATAACTACCTC AAAGGGGTCATAAAGCTCTTTGATAGAATATATAGCACTGGTTTGGGACGGATGCTGT TGAGTTTCATCGTTAAAGGAATACCATTCTGGGGCGGGTCAACAATCGACACCGAAC TCAAAGTAATAGACACTAATTGCATAAACGTTATAGAACCTGGCGGTTCTTATCGGTCA GAAGAGTTGAATCTTGTCATTACCGGACCTTCAGCCGACATAATACAGTTTGAATGTA AGTCATTTGGACATGATGTGTTTAATTTGACCCGCAATGGTTACGGTAGCACACAATAT ATAAGATTTTCACCAGATTTCACTTTTGGGTTTGAAGAAAGTCTTGAAGTGGATACGAACCCACTCCTTGGAGCTGGGACCTTCGCGACGGATCCCGCCGTGACGCTCGCGCACGAACTGATTCATGCCGCGCATAGACTGTATGGCATTGCGATTAACCCGAACAGGGTGCTCAAGGTGAAGACCAATGCCTATTACGAAATGAGTGGACTTGAAGTATCATTTGAGGAGCTGCGGACATTCGGGGGCAACGATACCAATTTCATAGATTCCTTGTGGCAAAAAAAGTTCAGCCGAGATGCCTATGATAATCTTCAGAATATAGCCAGGATACTGAATGAAGCAAAAACCATCGTGGGTACGACTACGCCTCTGCAGTATATGAAAAACATATTCATCCGAAAGTATTTTTTGTCTGAAGATGCGAGCGGGAAAATTTCAGTGAACAAACCCGCGTTTAAGGAATTTTATAGGGTCTTGACACGCGGTTTTACAGAACTGGAATTTGTAAATCCTTTTAAGGTGATAAACAGGAAAACGTACCTTAATTTTGACAAGGCTGTATTCCGGATCAATATCGTGCCAGATGAGAACTACACCATCAATGAGGGATTCAATCTCGAAGGTGCGAACTCCAATGGGCAGAACACGGAGATTAACAGCAGGAATTTCACTAGGCTGAAAAATTTCACGGGCCTGTTTGAGTTTTATAAGCTTCTCTGTGTTCGAGGAATCATACCGTTCAAGTGAGCGGCCGCTTAATTAAGCTGCCTTCTGCGGGGCTTGCCTTCTGGCCATGCCCTTCTTCTCTCCCTTGCACCTGTACCTCTTGGTCTTTGAATAAAGCCTGAGTAGGAAGAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAASEQ ID NO: 11, DNA, artificial, light chain botulinum, human optimized from StrainUPI00016DBC11TCGAGCTCGGTACCTAATACGACTCACTATAAGGAGGAAATAAGAGAGAAAAGAAGAGTAAGAAGAAATATAAGAGCCACCATGCCTTTCGTAAACAAGCAATTTAATTATAGAGATCCGGTAAACGGAGTTGATATTGCTTACATCAAGATCCCAAATGCAGGGCAGATGCAACCAGTCAAAGCGTTCAAAATCCATGAAGGCGTGTGGGTAATCCCGGAACGAGATACGTTTACCAATCCGGAAGAAGGCGACCTGAACCCGCCTCCAGAGGCGAAACAGGTCCCGGTGAGTTACTATGATTCCACCTACCTCAGTACTGACAATGAAAAGGATAATTATTTGAAAGGCGTGATTAAGCTCTTTGATCGGATATACTCTACTGGACTGGGGAGAATGCTCCTGTCTTTTATAGTAAAGGGAATCCCTTTTTGGGGAGGCAGTACTATTGATACCGAACTTAAGGTAATTGATACAAACTGCATCAACGTCATAGAGCCCGGAGGGAGCTACAGGTCCGAGGAACTCAATCTGGTCATTACCGGGCCCTCAGCTGATATTATTCAGTTCGAGTGCAAGTCATTTGGACACGATGTTTTTAACTTGACACGGAACGGATATGGGAGCACGCAGTACATCCGATTCTCACCGGACTTCACATTTGGATTCGAGGAGAGTCTGGAAGTGGATACAAATCCATTGCTTGGAGCTGGAACATTTGCAACGGATCCCGCTGTTACGCTCGCACACGAGCTTATTCACGCGGCCCACAGATTGTATGGAATCGCTATTAATCCCAATCGGGTGTTGAAGGTTAAAACAAATGCGTATTACGAAATGAGTGGTCTTGAAGTCTCTTTCGAGGAACTTCGAACATTTGGGGGGAACGATACCAATTTCATAGACTCCCTTTGGCAAAAAAAGTTTAGTAGAGACGCCTACGATAATCTCCAAAACATCGCGCGGATACTGAATGAGGCAAAGACGATCGTCGGTACAACGACACCACTCCAGTATATGAAAAACATTTTTATACGGAAGTATTTCCTTAGCGAAGATGCTTCCGGAAAGATCAGCGTAAACAAAGCTGCTTTTAAGGAATTCTATCGAGTGCTGACTCGCGGGTTTACGGAGCTGGAGTTTGTAAACCCGTTCAAGGTAATCAATCGAAAGACCTATCTGAACTTTGATAAGGCCGTCTTCAGAATAAACATAGTACCTGACGAAAATTACACAATCAATGAGGGATTTAATCTCGAGGGAGCGAATAGCAATGGTCAGAACACAGAAATAAATAGCCGAAATTTTACCCGACTTAAGAACTTTACCGGTCTCTTTGAGTTCTACAAACTCCTGTGTGTGAGAGGAATTATACCTTTTAAATAGGCGGCCGCTTAATTAAGCTGCCTTCTGCGGGGCTTGCCTTCTGGCCATGCCCTTCTTCTCTC CCTTGCACCTGTACCTCTTGGTCTTTGAATAAAGCCTGAGTAGGAAGAAAAAAAAAA AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA AAAAAAAAAAAAAAAASEQ ID NO: 12, DNA, artificial, light chain botulinum, human optimized from Strain UPI00005B712CTCGAGCTCGGTACCTAATACGACTCACTATAAGGAGGAAATAAGAGAGAAAAGAAGA GTAAGAAGAAATATAAGAGCCACCATGCCATTCGTGAACAAACCGTTCAACTACAGA GATCCAGGTAATGGTGTGGACATTGCGTACATCAAAATACCGAATGCGGGACAAATGC AGCCAGTTAAGGCTTTTAAAATTCATGAGGGGGTATGGGTGATTCCTGAACGCGACAC GTTCACTAATCCGGAGGAGGGCGATCTGAATCCCCCTCCTGAAGCCAAGCAGGTTCC AGTGAGTTACTATGACTCCACCTACCTCTCCACAGATAACGAGAAGGACAACTACCTT AAAGGTGTTATCAAGTTGTTCGACCGGATCTACAGCACAGGCCTGGGCCGAATGCTT CTCTCTTTTATAGTAAAGGGTATCCCGTTCTGGGGCGGTTCCACCATAGATACAGAACT GAAGGTAATCGATACAAACTGCATCAATGTAATCGAGCCTGGGGGGTCTTACCGAAGT GAGGAACTCAACCTTGTGATAACCGGGCCCTCCGCTGATATCATCCAGTTTGAGTGCA AATCTTTCGGGCATGATGTGTTCAATCTGACGCGCAATGGGTATGGGTCCACGCAATA CATTAGGTTCTCTCCCGACTTCACATTTGGATTCGAGGAGAGTCTCGAGGTAGACACGAACCCGCTTCTTGGTGCGGGAACTTTTGCCACTGATCCAGCGGTGACTCTCGCTCATG AACTCATTCATGCTGCACACCGCTTGTATGGAATCGCAATTAACCCCAACCGCGTCCT GAAAGTTAAAACTAACGCCTATTATGAGATGTCCGGCCTGGAGGTCTCTTTTGAGGAA CTCCGAACCTTTGGTGGGAATGACACCAACTTTATAGATAGTCTGTGGCAAAAAAAAT TCAGCCGAGACGCATATGATAACCTGCAGAATATTGCTAGGATCCTGAACGAGGCCAA AACCATTGTGGGAACCACCACCCCTCTGCAGTACATGAAAAATATTTTCATTCGGAAA TATTTCCTGAGTGAAGACGCGTCTGGGAAAATATCAGTAAATAAAGCGGCCTTCAAG GAGTTCTATAGAGTGCTTACAAGGGGTTTCACTGAATTGGAATTTGTGAATCCGTTCA AGGTGATTAATCGCAAAACCTACCTGAATTTTGACAAAGCCGTATTCAGAATTAACAT AGTACCTGATGAAAACTATACGATCAATGAGGGTTTCAATTTGGAAGGAGCAAATAGT AACGGCCAAAACACTGAGATCAACTCACGCAATTTTACTAGGCTTAAAAATTTCACTG GATTGTTTGAATTTTACAAACTGCTGTGTGTGCGCGGGATCATTCCATTTAAGTAAGCG GCCGCTTAATTAAGCTGCCTTCTGCGGGGCTTGCCTTCTGGCCATGCCCTTCTTCTCTC CCTTGCACCTGTACCTCTTGGTCTTTGAATAAAGCCTGAGTAGGAAGAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA AAAAAAAAAAAAAAAASEQ ID NO: 13, DNA, artificial, light chain botulinum, human optimized from Strain UPI0004A59983TCGAGCTCGGTACCTAATACGACTCACTATAAGGAGGAAATAAGAGAGAAAAGAAGA GTAAGAAGAAATATAAGAGCCACCATGCCTTTCGTGAATAAGCAGTTTAACTATAAGG ACCCGGTAAATGGAGTGGACATAGCATACATCAAGATCCCGAACGCTGGTCAAATGC AACCGGTTAAAGCATTTAAAATCCACAACAAGATCTGGGTAATTCCTGAGCGAGATAC GTTCACGAATCCGGAAGAAGGAGACCTCAACCCGCCTCCTGAGGCCAAGCAGGTGCCTGTATCATATTATGATTCAACCTATCTGTCTACAGACAATGAAAAAGATAACTACTTGAAGGGGGTCACTAAACTGTTCGAAAGAATCTATAGCACGGACTTGGGCAGAATGCTTCTTACCTCTATCGTGCGGGGCATACCCTTCTGGGGCGGTTCCACGATAGATACTGAACTGAAAGTCATAGACACTAACTGCATTAACGTGATACAACCGGACGGCTCTTATAGGAGCGAGGAACTGAACCTGGTTATCATAGGTCCCAGCGCAGACATCATCCAATTCGAGTGCAAAAGTTTCGGGCATGACGTCCTTAACCTTACAAGGAACGGATATGGTTCCACGCAGTATATTCGCTTCTCTCCTGACTTCACTTTTGGGTTCGAAGAGAGCCTTGAGGTAGACACAAATCCACTTTTGGGCGCTGGTAAATTCGCGACAGATCCCGCCGTCACGCTTGCACATGAGTTGATACATGCCGAACATCGCCTGTACGGGATTGCGATCAATCCAAACCGCGTATTCAAGGTCAACACGAATGCCTATTACGAAATGTCCGGTTTGGAGGTTTCATTTGAAGAACTTCGGACTTTTGGGGGGCACGACGCAAAATTCATCGACAGTCTCCAAGAGAACGAATTTCGACTGTACTACTACAATAAATTTAAAGATGTTGCATCTACCCTTAATAAGGCAAAATCCATTATAGGCACTACCGCAAGCCTTCAGTACATGAAAAATGTATTTAAAGAGAAATATTTGCTTTCTGAGGATACGTCAGGTAAGTTCTCTGTCGACAAGTTGAAGTTCGATAAACTGTATAAAATGTTGACTGAGATCTATACTGAGGACAATTTTGTGAACTTCTTCAAGGTCATAAACCGAAAGACGTATCTTAACTTCGACAAGGCAGTGTTCAGGATAAATATCGTACCGGATGAAAATTACACTATCAAAGATGGATTCAACCTCAAAGGGGCCAATCTTAGTACGAATTTTAACGGTCAAAACACGGAAATTAACAGCAGGAACTTCACTCGCCTGAAGAATTTCACGGGCCTGTTTGAATTTTACAAATTGCTGTGTGTGCGAGGAATAATACCATTTAAGTAGGCGGCCGCTTAATTAAGCTGCCTTCTGCGGGGCTTGCCTTCTGGCCATGCCCTTCTTCTCTCCCTTGCACCTGTACCTCTTGGTCTTTGAATAAAGCCTGAGTAGGAAGAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAASEQ ID NO: 14, DNA, artificial, light chain botulinum, human optimized from StrainUPI000290BEB 1TCGAGCTCGGTACCTAATACGACTCACTATAAGGAGGAAATAAGAGAGAAAAGAAGAGTAAGAAGAAATATAAGAGCCACCATGCCGTTCGTGAACAAACAATTCAACTACAAAGACCCTGTCAATGGAGTCGATATTGCTTACATTAAGATACCCAATGCCGGACAGATGCAGCCCGTCAAAGCCTTCAAGATACATAATAAGATATGGGTCATCCCGGAGCGGGACACCTTCACTAATCCCGAAGAGGGGGATCTTAACCCGCCACCCGAGGCGAAACAAGTACCTGTTAGCTATTACGATAGTACCTACTTGTCTACAGATAATGAGAAGGATAATTACCTGAAAGGTGTCACAAAACTGTTTGAACGCATATACCTCACCGATCTGGGGCGAATGCTCCTTACATCTATAGTAAGAGGAATACCTTTCTGGGGAGGAAGTACTATAGACACCGAACTTAAAGTGATCGACACGAACTGCATTAATGTCATACAGCCAGACGGCTCATACAGATCTGAGGAGCTCAATCTCGTAATCATCGGGCCTAGTGCGGACATCATTCAATTTGAGTGCAAGTCATTTGGCCACGATGTTCTTAATCTGACTCGAAACGGATATGGATCTACTCAATATATTCGGTTCTCACCCGATTTTACATTCGGCTTTGAGGAGTCTCTGGAAGTCGACACCAATCCACTGCTCGGCGCGGGAAAATTCGCAACGGACCCGGCTGTTACACTCGCACACGAACTGATTCACGCAGAACACAGGCTCTATGGCATAGCCATAAACCCCAATCGCGTGTTTAAAGTTAACACCAATGCTTATTATGAAATGAGCGGGCTGGAGGTTAGCTTCGAGGAGTTGCGGACTTTTGGGGGACATGATGCCAAGTTCATAGATTCCTTGCAAGAGAATGAGTTTCGGCTTTATTACTATAATAAATTTAAGGACGTCGCGTCTACACTCAACAAGGCAAAAAGTATTATTGGTACAACAGCGTCCCTGCAATACATGAAGAATGTCTTTAAAGAAAAGTACCTTTTGTCCGAAGATACCTCTGGAAAGTTTTCCGTCGATAAGCTCAAGTTTGACA AGCTTTATAAAATGCTTACTGAGATCTACACCGAAGATAATTTCGTCAATTTCTTCAAG GTGATCAATCGCAAAACATACCTGAATTTCGACAAGGCGGTTTTCAGAATTAACATTG TCCCGGACGAAAACTACACGATCAAAGACGGCTTCAACCTGAAAGGTGCCAACCTGTCAACCAATTTCAATGGTCAAAATACTGAGATCAATAGTCGGAATTTTACCCGCCTGAAAAACTTTACCGGGCTTTTTGAATTCTACAAGCTTCTGTGCGTGCGGGGAATAATTCC GTTCAAATGAGCGGCCGCTTAATTAAGCTGCCTTCTGCGGGGCTTGCCTTCTGGCCAT GCCCTTCTTCTCTCCCTTGCACCTGTACCTCTTGGTCTTTGAATAAAGCCTGAGTAGG AAGAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAASEQ ID NO: 15, DNA, artificial, light chain botulinum, human optimized from Strain UPI000290BDD5TCGAGCTCGGTACCTAATACGACTCACTATAAGGAGGAAATAAGAGAGAAAAGAAGAGTAAGAAGAAATATAAGAGCCACCATGCCATTTGTGAACAAACAATTCAATTACAAA GACCCAGTAAATGGAGTCGACATAGCGTATATAAAGATACCCAATGCGGGCCAGATGC AGCCAGTGAAAGCTTTTAAAATACACAATAAAATCTGGGTGATTCCGGAGCGGGACA CGTTTACGAATCCGGAAGAGGGGGATCTGAACCCGCCACCTGAGGCGAAACAAGTACCAGTATCATACTATGACAGCACGTATCTTAGCACCGATAACGAAAAGGACAACTATCTGAAAGGCGTCACGAAACTCTTTGAGCGAATTTACTCTACGGACCTTGGAAGAATGC TTTTGACGAGCATCGTTCGCGGTATTCCGTTTTGGGGAGGGTCCACGATCGACACTGA ACTCAAAGTAATAGACACCAATTGTATTAATGTCATTCAGCCAGACGGCTCCTATCGA AGTGAGGAGCTTAATCTCGTAATCATAGGACCCAGTGCTGATATTATCCAGTTTGAATGTAAGAGTTTCGGACATGATGTCCTTAATCTGACCCGGAATGGGTATGGATCCACGCAGTATATCCGATTTTCCCCTGATTTTACATTTGGATTCGAGGAGTCACTTGAAGTGGATACGAACCCGCTTTTGGGAGCCGGGAAGTTTGCTACCGATCCTGCAGTCACTCTGGCCCATGAGCTCATACATGCCGAGCACCGACTGTATGGGATAGCCATAAATCCCAATAGGGTCTTCAAGGTTAACACGAACGCATATTATGAAATGAGTGGTCTTGAAGTCTCATTCGAAGAACTGCGGACATTTGGGGGCCATGATGCCAAGTTTATTGACTCATTGCAGGAAAACGAATTTCGCCTTTACTACTATAATAAATTTAAAGACGTCGCAAGTACTCTCAACAAGGCCAAAAGTATTATAGGAACTACCGCATCTCTGCAGTACATGAAAAATGTGTTCAAGGAGAAGTATTTGCTGTCTGAGGATACCAGTGGGAAATTCTCTGTCGACAAGCTTAAGTTTGACAAACTTTACAAGATGTTGACTGAAATATACACGGAAGACAATTTTGTCAACTTTTTC AAAGTAATTAACCGAAAAACGTATTTGAACTTCGATAAAGCTGTATTTAGGATCAACA TCGTACCAGACGAGAATTATACCATCAAAGATGGCTTCAACCTGAAGGGGGCCAATCT CTCTATCAACTTTAACGGACAAAATACAGAGATAAACAGCCGCAACTTCACGCGCCTGAAAAACTTTACTGGTCTGTTCGAATTCTATAAGCTGCTTTGTGTACGAGGCATAATACCATTTAAGTAGGCGGCCGCTTAATTAAGCTGCCTTCTGCGGGGCTTGCCTTCTGGCCA TGCCCTTCTTCTCTCCCTTGCACCTGTACCTCTTGGTCTTTGAATAAAGCCTGAGTAGG AAGAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA AAAAAAAAAAAAAAAAAAAAAAAAAAAAASEQ ID NO: 16, DNA, artificial, light chain botulinum, human optimized from Strain UPI0001F3B30DTCGAGCTCGGTACCTAATACGACTCACTATAAGGAGGAAATAAGAGAGAAAAGAAGAGTAAGAAGAAATATAAGAGCCACCATGCCTTTTGTAAACAAGCAGTTTAATTATAAAGACCCAGTCAACGGGGTCGACATAGCATATATTAAGATCCCGAATGCCGGCCAAATGCAACCCGTGAAAGCTTTCAAGATCCATAATAAAATATGGGTTATTCCAGAAAGAGACACC TTCACGAATCCAGAAGAAGGCGATCTTAATCCCCCTCCTGAAGCGAAACAGGTTCCCGTATCTTACTATGATAGTACGTACTTGAGTACCGACAACGAAAAGGATAATTACCTCAAAGGGGTCACTAAGCTTTTTGAGAGGATTTATTCAACTGATCTGGGACGGATGCTGCTTACTAGCATTGTTCGCGGGATTCCCTTTTGGGGAGGTTCTACTATAGACACAGAGCTCAAAGTGATTGATACTAATTGCATAAACGTAATTCAACCAGATGGATCATATAGGAGTGAAGAGTTGAATCTTGTCATCATAGGCCCGAGCGCGGATATTATTCAGTTTGAGTGCAAAAGTTTCGGCCACGACGTGCTGAATCTGACCCGAAATGGCTATGGCAGCACCCAGTATATCCGGTTTAGCCCGGACTTCACATTCGGCTTCGAGGAGTCTTTGGAAGTCGACACAAACCCACTGTTGGGGGCCGGTGAGTTTGCTACAGACCCTGCAGTTACACTCGCCCACGA GCTTATCCATGCCGAGCATCGCTTGTACGGAATAGCGATAAATCCGAATAGAGTATTCAAAGTAAACACAAACGCGTATTATGAAATGAGCGGACTTGAAGTGTCATTCGAGGAGCTCCGCACATTCGGTGGACATGATGCAAAATTTATAGACTCCCTTCAAGAGAATGAATTTAGATTGTACTATTATAACAAGTTTAAAGATGTGGCTAGTACCTTGAATAAAGCTAAGAGTATTATCGGCACAACCGCCAGCCTTCAGTACATGAAAAATGTCTTTAAAGAAAAGTATCTTCTGTCAGAAGACACTTCCGGTAAGTTTAGCGTAGACAAACTTAAATTTGACAAATTGTATAAGATGTTGACTGAGATCTATACAGAGGATAACTTCGTTAACTTTTTTAAAGTGATAAATAGAAAGACATATCTCAATTTCGATAAGGCCGTCTTTCGCATCAATATAGTAC CGGACGAAAACTATACGATAAAGGATGGATTCAACCTGAAGGGAGCGAATCTCAGCA CCAATTTCAACGGGCAGAATACCGAAATCAACTCTCGGAATTTTACGAGACTCAAAAATTTCACAGGTCTCTTCGAATTTTACAAACTGCTGTGTGTTCGCGGTATCATTCCATTTAAGTAGGCGGCCGCTTAATTAAGCTGCCTTCTGCGGGGCTTGCCTTCTGGCCATGCCCTTCTTCTCTCCCTTGCACCTGTACCTCTTGGTCTTTGAATAAAGCCTGAGTAGGAAGAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAASEQ ID NO: 17, DNA, artificial, light chain botulinum, human optimized from Strain UPI0001C32E84TCGAGCTCGGTACCTAATACGACTCACTATAAGGAGGAAATAAGAGAGAAAAGAAGAGTAAGAAGAAATATAAGAGCCACCATGCCCTTTGTTAATAAACAGTTTAACTACAAAGACCCGGTCAACGGGGTGGACATAGCATACATCAAGATACCCAACGCGGGGCAGATGCAACCCGTGAAAGCGTTCAAGATACACAACAAAATTTGGGTCATTCCTGAAAGAGACACCTTTACAAACCCGGAAGAGGGTGATCTCAATCCACCACCTGAAGCTAAACAAGTACCAGTCTCTTACTATGACTCAACGTACCTTAGCACGGACAATGAGAAGGATAACTATCTGAAGGGGGTCACAAAGTTGTTTGAGAGAATTTATAGTACAGACTTGGGTCGCATGCT CCTTACAAGCATAGTACGCGGGATTCCGTTCTGGGGGGGCAGTACTATTGATACGGAGCTTAAGGTAATTGATACGAACTGCATTAACGTGATTCAGCCAGACGGCAGTTACCGCTCTGAAGAACTGAATCTGGTAATTATAGGCCCGTCTGCGGATATAATTCAATTTGAATGC AAGAGTTTTGGCCACGATGTTCTTAACCTGACGCGCAATGGCTACGGAAGCACACAG TACATAAGATTCAGTCCAGATTTCACTTTTGGCTTCGAGGAGTCATTGGAAGTGGATA CGAACCCTCTGTTGGGGGCTGGCAAATTTGCAACCGACCCAGCGGTTACTCTGGCAC ATGAGCTCATTCACGCTGAACATCGCTTGTATGGGATAGCTATCAACCCCAATCGCGTT TTTAAAGTCAATACTAACGCTTATTATGAGATGAGTGGGCTGGAAGTCTCTTTTGAGG AATTGCGCACGTTTGGTGGCCATGATGCTAAGTTTATAGACTCCCTTCAGGAAAACGA ATTCAGACTCTACTATTACAATAAATTTAAAGATGTAGCTTCTACCCTGAACAAAGCGA AGTCTATCATTGGAACAACCGCAAGTCTGCAGTACATGAAGAATGTCTTTAAGGAGA AGTACCTTCTGTCCGAGGATACCTCTGGAAAATTCAGTGTCGACAAGCTCAAATTTGA TAAACTCTATAAGATGCTCACAGAGATATATACCGAGGATAATTTTGTCAACTTCTTTA AGGTTATTAATAGGAAAACGTACCTGAACTTTGATAAGGCCGTCTTCCGAATAAATATT GTACCGGATGAGAATTACACTATTAAGGATGGTTTCAATCTTAAGGGCGCAAATCTCAGCACGAATTTCAATGGCCAAAATACAGAGATTAATTCTAGAAATTTCACTAGACTGAAAAATTTCACAGGATTGTTTGAGTTTTACAAACTCCTTTGCGTTCGAGGGATAATTCCG TTCAAGTAAGCGGCCGCTTAATTAAGCTGCCTTCTGCGGGGCTTGCCTTCTGGCCATG CCCTTCTTCTCTCCCTTGCACCTGTACCTCTTGGTCTTTGAATAAAGCCTGAGTAGGA AGAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAASEQ ID NO: 18, DNA, artificial, light chain botulinum, human optimized from Strain UPI0001C0B376TCGAGCTCGGTACCTAATACGACTCACTATAAGGAGGAAATAAGAGAGAAAAGAAGAGTAAGAAGAAATATAAGAGCCACCATGCCTTTTGTAAATAAACAGTTTAACTATAAGGATCCAGTAAATGGCGTAGATATTGCCTACATAAAGATACCGAATGCAGGTCAGATGCAACCAGTTAAGGCTTTTAAGATCCACAATAAGATTTGGGTTATACCTGAAAGGGATACA TTCACAAATCCGGAGGAGGGTGATCTGAATCCTCCTCCAGAAGCAAAGCAAGTGCCA GTATCATATTATGATAGCACTTACCTTAGCACAGATAACGAGAAAGATAATTACTTGAA GGGAGTAACTAAACTCTTCGAAAGAATCTATTCCACAGATCTTGGTCGCATGTTGCTTACTTCTATAGTACGCGGGATACCGTTCTGGGGTGGTTCCACAATTGACACCGAACTTA AGGTCATTGATACCAACTGTATCAACGTCATTCAGCCTGACGGAAGTTACCGGAGTGA AGAGTTGAACCTCGTCATCATAGGTCCCAGCGCAGATATAATTCAGTTCGAGTGTAAA AGTTTCGGGCATGATGTATTGAATCTTACCAGGAATGGGTACGGCTCAACGCAATATATCAGATTCTCACCCGATTTTACTTTCGGTTTTGAAGAATCCTTGGAAGTAGATACTAATC CACTTCTCGGCGCGGGTAAATTTGCAACTGATCCTGCTGTCACTCTTGCGCACGAACT TATACACGCCGAACATAGATTGTACGGCATCGCCATCAACCCCAACCGGGTTTTTAAA GTCAACACGAATGCGTACTATGAGATGTCTGGTCTGGAAGTGAGTTTCGAGGAATTGAGGACTTTCGGCGGTCACGACGCAAAGTTCATAGACAGCCTTCAGGAGAACGAATTCAGGTTGTACTATTACAATAAGTTCAAAGACGTCGCGAGTACGCTGAATAAGGCCAAGAGCATTATTGGGACAACCGCTTCCCTTCAGTACATGAAGAACGTGTTCAAGGAAAAA TATCTCTTGTCCGAAGATACGTCCGGCAAGTTCTCCGTCGACAAGTTGAAATTTGATA AATTGTATAAGATGCTGACAGAGATATATACTGAGGATAATTTCATCAATTTCTTCAAA GTGATTAATAGGAAAACTTATCTTAATTTCGATAAGGCAGTGTTCAGAATCAATATTGTGCCTGACGAGAATTATACCATCAAAGACGGTTTCAACCTCAAGGGTGCCAACCTCTCAACTAACTTTAATGGGCAAAACACGGAAATTAACAGCAGAAATTTCACACGATTGAAAAATTTTACTGGACTTTTTGAATTCTACAAGCTCCTGTGCGTTAGGGGGATCATACCTTTCAAATAAGCGGCCGCTTAATTAAGCTGCCTTCTGCGGGGCTTGCCTTCTGGCCATGCCCTTCTTCTCTCCCTTGCACCTGTACCTCTTGGTCTTTGAATAAAGCCTGAGTAGGAAGAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAASEQ ID NO: 19, DNA, artificial, light chain botulinum, human optimized from StrainUPI0000EF84BDTCGAGCTCGGTACCTAATACGACTCACTATAAGGAGGAAATAAGAGAGAAAAGAAGAGTAAGAAGAAATATAAGAGCCACCATGCCTTTTGTCAATAAACAGTTTAACTATAAAGACCCTGTAAATGGTGTAGACATCGCCTACATTAAGATACCAAATGCGGGGCAGATGCAGCCGGTAAAAGCATTTAAGATCCATAACAAGATATGGGTAATCCCCGAGCGGGATACATTCACCAATCCGGAGGAAGGTGATCTTAACCCACCTCCTGAGGCTAAACAAGTTCCCGTATCCTATTACGATAGCACATACTTGTCAACTGACAATGAAAAAGATAACTACCTGAAAGGCGTGACTAAACTCTTTGAACGGATCTACTCTACTGATCTCGGTCGAATGTTGCTGACTTCAATAGTGAGGGGCATCCCCTTCTGGGGGGGCTCAACTATCGACACGGAACTGAAGGTCATTGATACTAACTGCATCAATGTCATCCAACCCGATGGTTCCTATAGGAGTGAGGAGCTCAATCTGGTAATAATCGGTCCCTCAGCCGATATCATTCAGTTTGAGTGTAAATCATTCGGCCACGATGTCTTGAATCTGACTAGAAACGGTTATGGGTCAACGCAATACATCAGATTCTCCCCCGATTTCACCTTTGGGTTCGAGGAGAGTCTCGAGGTGGACACGAATCCGCTCCTGGGCGCTGGTAAGTTCGCGACAGATCCAGCGGTAACTCTTGCACATGAGTTGATTCACGCAGAGCATAGGCTGTACGGGATAGCTATTAACCCCAACCGCGTATTTAAGGTGAACACGAACGCATATTATGAGATGTCCGGATTGGAGGTGAGCTTCGAAGAACTGAGGACGTTTGGTGGTCACGATGCTAAATTTATTGATAGCTTGCAAGAAAACGAATTTAGACTGTATTACTATAACAAGTTCAAGGACGTAGCGTCAACCCTTAATAAGGCTAAAAGCATAATAGGGACAACAGCGTCCCTCCAATATATGAAAAACGTATTTAAAGAGAAATATCTTTTGAGCGAAGATACTAGCGGTAAATTCAGTGTTGACAAATTGAAATTCGATAAATTGTACAAAATGCTCACTGAGATATATACTGAGGATAACTTCGTTAATTTCTTTAAAGTTATAAACAGAAAGACCTATCTTAATTTCGATAAGGCTGTGTTTAGGATAAATATAGTTCCTGATGAAAACTACACTATCAAAGATGGTTTTAACCTGAAGGGTGCGAACCTTTCAACTAATTTTAACGGGCAGAATACGGAAATTAATTCTCGAAATTTCACTAGACTTAAAAATTTTACGGGCCTCTTTGAATTCTACAAACTGCTTTGTGTAAGAGGAATCATTCCCTTCAAGTAAGCGGCCGCTTAATTAAGCTGCCTTCTGCGGGGCTTGCCTTCTGGCCATGCCCTTCTTCTCTCCCTTGCACCTGTACCTCTTGGTCTTTGAATAAAGCCTGAGTAGGAAGAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAASEQ ID NO: 20, DNA, artificial, light chain botulinum, human optimized from StrainUPI000067C53ETCGAGCTCGGTACCTAATACGACTCACTATAAGGAGGAAATAAGAGAGAAAAGAAGAGTAAGAAGAAATATAAGAGCCACCATGCCCTTTGTGAATAAACAGTTTAACTATAAAGATCCCGTAAATGGGGTTGATATAGCTTACATTAAAATCCCCAATGCAGGGCAAATGCA ACCTGTCAAGGCTTTTAAGATACACAACAAGATCTGGGTAATTCCTGAGAGGGATACA TTTACGAATCCAGAAGAGGGAGATCTTAACCCTCCTCCAGAAGCCAAGCAGGTACCA GTATCCTATTACGATAGTACGTACCTTTCTACGGATAACGAGAAAGATAATTATCTTAA GGGAGTCACGAAACTGTTTGAGCGCATATATAGCACGGACCTTGGTAGAATGCTCCTT ACTAGCATCGTTAGAGGCATACCCTTCTGGGGTGGAAGTACAATCGACACAGAGCTG AAGGTGATAGACACAAATTGCATAAACGTCATCCAGCCGGACGGTTCCTACAGGAGT GAAGAACTCAACTTGGTTATAATTGGACCAAGTGCAGACATAATACAGTTTGAATGTA AATCATTTGGCCACGATGTGTTGAACCTGACCAGAAATGGTTATGGTTCCACCCAATA CATTCGGTTCAGCCCTGACTTTACGTTTGGCTTCGAGGAATCTTTGGAGGTGGATACG AATCCACTGCTTGGAGCTGGAAAATTTGCGACGGATCCCGCCGTCACACTGGCCCATGAACTGATCCACGCGGAGCACCGACTCTACGGAATCGCAATAAACCCCAATCGGGTT TTCAAAGTAAACACCAATGCGTATTATGAAATGAGCGGACTTGAGGTTTCATTCGAGG AGCTTAGAACATTCGGGGGCCATGACGCGAAATTCATAGATTCTCTGCAAGAAAATG AGTTCAGACTCTACTACTACAACAAGTTCAAGGACGTCGCGTCCACACTTAACAAGG CGAAATCAATCATTGGGACGACGGCATCCCTTCAATATATGAAGAACGTATTCAAGGA AAAGTATCTCCTGTCCGAAGATACTTCCGGAAAATTTAGTGTCGACAAACTCAAGTTTGATAAGCTCTACAAAATGCTCACTGAAATTTATACAGAGGATAACTTCGTAAACTTTTT CAAAGTGATCAACAGAAAAACATATCTGAATTTCGATAAAGCAGTTTTCCGAATTAAC ATCGTACCTGACGAGAATTATACCATAAAAGACGGCTTCAATCTGAAAGGGGCCAATC TCAGCATAAACTTTAATGGACAGAATACGGAGATAAACTCTAGAAATTTCACACGACT GAAAAACTTTACTGGCCTTTTCGAATTTTATAAACTTCTGTGCGTGAGGGGCATTATAC CCTTTAAGTGAGCGGCCGCTTAATTAAGCTGCCTTCTGCGGGGCTTGCCTTCTGGCCATGCCCTTCTTCTCTCCCTTGCACCTGTACCTCTTGGTCTTTGAATAAAGCCTGAGTAGG AAGAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA AAAAAAAAAAAAAAAAAAAAAAAAAAAAASEQ ID NO: 21, DNA, artificial, light chain botulinum, human optimized from Strain UPI000016EA88TCGAGCTCGGTACCTAATACGACTCACTATAAGGAGGAAATAAGAGAGAAAAGAAGA GTAAGAAGAAATATAAGAGCCACCATGCCCTTCGTGAACAAACAGTTTAATTATAAGG ACCCAGTTAACGGAGTGGACATAGCGTATATTAAGATTCCTAACGCGGGTCAAATGCA GCCTGTAAAGGCGTTCAAAATACATAACAAGATTTGGGTGATACCAGAGCGGGATAC ATTCACAAATCCTGAAGAAGGTGATCTTAACCCACCTCCGGAAGCGAAACAGGTCCC GGTATCATACTACGATTCAACATATCTGTCTACTGATAACGAGAAGGATAATTATTTGAAGGGTGTCACTAAGTTGTTTGAACGGATTTACAGCACTGACTTGGGTCGGATGCTGCT TACTTCAATCGTACGGGGCATTCCTTTCTGGGGTGGCAGTACAATAGATACAGAGCTG AAAGTAATAGATACCAATTGCATCAATGTAATCCAACCTGATGGTAGCTATCGCTCTGA GGAACTTAACTTGGTGATTATCGGACCCTCCGCAGACATTATCCAGTTTGAATGTAAG TCCTTCGGCCACGACGTATTGAATTTGACGCGGAACGGCTATGGCTCCACGCAATACA TACGCTTCAGCCCGGACTTCACGTTTGGATTCGAGGAGAGCTTGGAGGTGGATACGAATCCGCTCCTTGGGGCTGGGAAGTTCGCTACAGATCCTGCCGTAACCCTCGCGCATGA GCTTATCCATGCGGAGCACCGACTCTATGGGATAGCGATTAACCCGAACAGGGTATTTAAAGTGAATACGAACGCCTACTACGAAATGAGTGGCCTCGAGGTTAGCTTTGAAGAGTTGCGCACTTTCGGAGGTCATGACGCTAAGTTCATAGATTCACTGCAGGAGAATGAGTTTCGCCTTTATTATTACAACAAGTTCAAAGATGTGGCTTCTACGCTGAACAAGGCGAAAAGCATAATAGGCACCACTGCTTCCCTCCAGTATATGAAGAACGTCTTTAAAGAAAAATACCTCTTGTCTGAGGATACCAGCGGCAAATTTAGTGTGGACAAGCTGAAATTTGATAAACTCTATAAAATGCTTACCGAGATATATACCGAGGACAACTTCGTAAACTTTTTCAAGGTTATAAACAGGAAGACGTACTTGAACTTTGACAAGGCGGTGTTTAGAATCAACATTGTTCCTGACGAGAACTATACTATCAAAGATGGATTTAATTTGAAGGGCGCGAATTTGTCTACCAACTTTAATGGTCAAAATACAGAGATTAACTCACGAAATTTTACCCGGCTTAAGAACTTTACGGGTCTTTTCGAGTTTTATAAGCTGCTGTGCGTCAGAGGGATCATACCCTTCAAGTGAGCGGCCGCTTAATTAAGCTGCCTTCTGCGGGGCTTGCCTTCTGGCCATGCCCTTCTTCTCTCCCTTGCACCTGTACCTCTTGGTCTTTGAATAAAGCCTGAGTAGGAAGAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAASEQ ID NO: 22, DNA, artificial, light chain botulinum, human optimized from StrainUPI00027EE164TCGAGCTCGGTACCTAATACGACTCACTATAAGGAGGAAATAAGAGAGAAAAGAAGAGTAAGAAGAAATATAAGAGCCACCATGCCATTTGTCAACAAACAGTTCAACTATAAAGACCCAGTAAATGGAGTCGATATCGCTTACATTAAGATTCCGAATGCGGGTCAAATGCAGCCGGTCAAAGCCTTCAAGATACACAACAAGATCTGGGTGATTCCTGAAAGGGACACGTTCACCAACCCAGAAGAAGGCGACTTGAACCCACCTCCCGAAGCTAAACAAGTGCCAGTTAGCTACTATGATTCTACATACCTCAGTACAGATAACGAAAAAGACAACTACTTGAAAGGAGTGACGAAGTTGTTTGAAAGAATTTATTCAACAGATTTGGGGCGAATGCTCCTTACCTCCATTGTAAGGGGCATTCCTTTTTGGGGAGGCTCTACCATCGACACAGAGCTGAAGGTAATAGACACTAATTGCATCAATGTAATACAGCCAGATGGGTCTTATCGCTCCGAAGAGCTGAACTTGGTAATCATTGGCCCTAGTGCTGACATTATACAGTTTGAGTGCAAAAGCTTCGGTCACGAGGTACTGAATCTCACGCGGAATGGGTACGGGTCAACGCAATACATTCGCTTCAGCCCAGACTTCACTTTTGGTTTCGAAGAGTCCCTTGAGGTTGACACTAATCCACTTCTCGGTGCTGGTAAGTTTGCCACGGACCCAGCTGTGACGCTGGCACATGAGCTCATACACGCTGGTCATAGACTCTACGGGATCGCCATCAACCCAAATCGGGTCTTCAAAGTAAATACTAATGCATATTATGAGATGTCTGGGCTCGAAGTGTCTTTCGAGGAGCTCCGAACATTTGGCGGCCACGATGCGAAATTTATTGACAGTCTCCAGGAAAACGAGTTTCGACTTTACTATTACAATAAATTTAAAGACATTGCATCCACCCTTAACAAGGCCAAATCTATTGTAGGTACAACTGCGTCCCTTCAGTACATGAAGAATGTTTTCAAAGAAAAATATCTCCTGTCTGAGGATACGTCCGGCAAGTTTAGTGTAGACAAATTGAAGTTCGATAAACTGTACAAGATGCTCACAGAAATTTATACGGAAGACAATTTTGTTAAGTTCTTCAAAGTGCTCAACCGCAAGACGTACCTCAACTTCGACAAGGCTGTTTTTAAAATCAACATCGTGCCGAAGGTCAACTACACAATATACGACGGGTTCAACCTGAGGAATACTAATTTGGCGGCCAACTTTAACGGCCAAAACACAGAAATAAACAACATGAACTTTACTAAACTGAAGAACTTCACCGGCCTCTTCGAGTTTTACAAGCTTCTCTGTGTTAGGGGCATCATCACGAGCAAATAGGCGGCCGCTTAATTAAGCTGCCTTCTGCGGGGCTTGCCTTCTGGCCATGCCCTTCTTCTCTCCCTTGCACCTGTACCTCTTGGTCTTTGAATAAAGCCTGAGTAGGAAGAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAASEQ ID NO: 23, DNA, artificial, light chain botulinum, human optimized from Strain UPI0001A954C8TCGAGCTCGGTACCTAATACGACTCACTATAAGGAGGAAATAAGAGAGAAAAGAAGA GTAAGAAGAAATATAAGAGCCACCATGCCTTTTGTCAACAAGCAGTTTAATTATAAGG ATCCCGTCAATGGAGTCGATATCGCATATATAAAGATTCCCAACGCAGGCCAAATGCA GCCGGTTAAAGCTTTCAAAATACACAATAAGATATGGGTTATACCAGAGCGCGACACC TTCACCAATCCGGAAGAGGGCGACCTGAATCCTCCCCCGGAAGCTAAGCAGGTGCCC GTTTCATATTACGACTCTACTTACTTGAGTACTGACAATGAGAAAGATAATTACTTGAA GGGCGTAACAAAATTGTTTGAAAGAATATACTCTACAGACTTGGGACGGATGCTTCTC ACAAGTATCGTTAGGGGAATACCTTTCTGGGGCGGGTCAACTATAGACACGGAGTTG AAAGTTATTGACACAAACTGCATCAATGTCATACAGCCCGACGGTTCCTACAGATCCG AGGAGCTTAACCTTGTAATAATAGGTCCATCTGCTGACATTATCCAGTTTGAATGCAAA TCCTTCGGCCATGAGGTCCTGAATCTCACGAGGAACGGCTATGGCTCCACGCAATATA TTCGCTTTTCTCCAGACTTTACCTTTGGTTTTGAGGAAAGTCTCGAGGTAGACACGAA CCCACTTCTTGGCGCGGGAAAGTTCGCGACAGATCCTGCGGTGACGCTTGCTCATGA ATTGATCCACGCTGGTCATCGGCTTTACGGGATTGCCATCAATCCAAACCGCGTATTCA AAGTCAACACTAACGCTTACTATGAGATGAGCGGGTTGGAGGTTTCTTTTGAGGAAC TTCGCACATTCGGCGGGCACGACGCGAAGTTCATCGACAGCCTGCAGGAGAATGAGT TTCGACTTTATTACTACAACAAGTTTAAAGATATTGCATCTACCCTTAATAAGGCGAAA AGTATCGTCGGAACCACCGCTAGTTTGCAATACATGAAAAATGTATTTAAGGAAAAGT ACCTTTTGTCCGAGGACACCTCAGGGAAGTTCTCCGTGGACAAACTCAAATTTGATA AACTGTACAAGATGCTCACAGAGATTTACACGGAGGATAATTTTGTAAAGTTCTTTAA AGTACTGAACCGCAAAACATACCTGAACTTCGACAAGGCCGTCTTCAAGATAAATATC GTACCCAAGGTTAATTATACTATCTACGACGGGTTCAACCTTCGCAATACAAATCTCGC AGCGAACTTCAACGGTCAAAATACAGAAATTAACAATATGAACTTTACGAAATTGAA AAATTTCACAGGTTTGTTTGAATTCTACAAGCTTCTTTGTGTTAGAGGCATAATAACCT CAAAATGAGCGGCCGCTTAATTAAGCTGCCTTCTGCGGGGCTTGCCTTCTGGCCATGCCCTTCTTCTCTCCCTTGCACCTGTACCTCTTGGTCTTTGAATAAAGCCTGAGTAGGAA GAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA AAAAAAAAAAAAAAAAAAAAAAAAAAASEQ ID NO: 24, DNA, artificial, light chain botulinum, human optimized from Strain UPI00016529B7TCGAGCTCGGTACCTAATACGACTCACTATAAGGAGGAAATAAGAGAGAAAAGAAGA GTAAGAAGAAATATAAGAGCCACCATGCCCTTCGTCAACAAGCAGTTTAATTATAAGG ATCCAGTTAATGGAGTCGACATCGCATACATTAAAATCCCAAATGTTGGGCAAATGCA GCCAGTAAAAGCCTTTAAGATTCATAACAAAATATGGGTGATACCGGAACGCGATACC TTTACGAATCCCGAAGAGGGGGATTTGAATCCACCACCCGAGGCAAAACAGGTACCT GTATCCTATTATGACTCAACATATTTGTCTACGGATAACGAAAAAGATAACTATTTGAA GGGTGTCACAAAACTGTTTGAGCGCATATACTCCACGGATCTCGGTCGAATGCTCTTGACTTCCATAGTAAGGGGTATACCTTTTTGGGGAGGGTCAACAATTGATACAGAGCTGAAGGTTATCGATACGAACTGCATAAATGTAATACAACCAGATGGCAGCTACAGATCTGAAGAGCTGAACCTTGTGATTATAGGACCATCCGCAGATATAATCCAATTCGAGTGTAAATCATTCGGTCACGAAGTTCTTAATCTTACTAGAAATGGATATGGCAGTACACAATACATTAGGTTCAGTCCTGACTTCACATTCGGGTTTGAGGAATCCCTCGAAGTAGACACGAACCCCCTGCTTGGCGCAGGAAAATTCGCGACTGACCCAGCTGTAACATTGGCTCACGAGCTTATTCACGCGGGCCACCGCCTGTACGGCATCGCTATAAACCCCAACAGGGTCTTCAAGGTGAATACGAATGCTTATTATGAAATGAGCGGGCTCGAAGTAAGCTTTGAAGAGCTTCGAACCTTCGGGGGCCATGACGCTAAGTTCATTGATTCCCTGCAGGAGAACGAATTTCGGTTGTACTACTACAACAAGTTTAAAGATATCGCTTCCACCCTCAACAAGGCGAAGTCAATAGTCGGCACTACAGCAAGCCTCCAGTACATGAAAAACGTCTTTAAGGAAAAATACCTCTTGAGCGAGGATACCAGTGGCAAATTTTCAGTGGACAAGCTTAAATTCGACAAATTGTACAAGATGCTCACAGAGATTTACACCGAGGATAATTTCGTAAAATTCTTTAAAGTTTTGAATCGGAAGACATATCTCAACTTTGACAAGGCAGTGTTCAAGATAAACATTGTTCCCAAGGTTAATTACACAATCTACGATGGATTCAATCTGAGAAATACCAACCTTGCAGCAAATTTTAATGGGCAAAATACTGAAATTAACAACATGAATTTCACGAAGCTTAAAAACTTTACAGGATTGTTCGAGTTTTACAAACTCCTGTGTGTACGGGGTATAATCACTAGCAAATAAGCGGCCGCTTAATTAAGCTGCCTTCTGCGGGGCTTGCCTTCTGGCCATGCCCTTCTTCTCTCCCTTGCACCTGTACCTCTTGGTCTTTGAATAAAGCCTGAGTAGGAAGAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAASEQ ID NO: 25, DNA, artificial, light chain botulinum, human optimized from StrainUPI0000EF85BDTCGAGCTCGGTACCTAATACGACTCACTATAAGGAGGAAATAAGAGAGAAAAGAAGAGTAAGAAGAAATATAAGAGCCACCATGCCTTTTGTCAATAAGCAGTTCAATTATAAAGACCCAGTGAATGGAGTGGATATTGCCTACATAAAAATCCCAAACGTAGGACAAATGCAACCTGTTAAAGCCTTTAAGATCCACAATAAGATTTGGGTTATACCTGAGCGAGACACCTTCACAAATCCTGAGGAGGGTGATTTGAACCCTCCGCCAGAAGCGAAGCAAGTGCCCGTAAGCTATTACGATAGTACGTACCTGTCCACAGACAATGAGAAAGATAACTACCTGAAGGGGGTAACGAAACTGTTCGAACGAATATATTCCACTGACCTTGGAAGAATGCTTCTGACTTCTATCGTAAGGGGCATCCCATTTTGGGGTGGGAGCACAATTGATACCGAGCTGAAGGTCATCGATACAAACTGTATAAACGTGATACAGCCCGACGGCTCATATCGGAGCGAGGAGCTGAATTTGGTAATCATCGGACCCTCAGCCGACATAATTCAATTTGAGTGTAAATCCTTCGGGCACGAGGTGTTGAATCTCACGCGCAATGGCTACGGTTCAACCCAGTATATAAGGTTCTCACCAGACTTTACTTTTGGGTTTGAGGAGTCCTTGGAAGTGGATACCAATCCACTCCTCGGTGCTGGAAAATTCGCCACCGATCCAGCAGTTACGTTGGCCCATGAATTGATTCATGCCGGCCATCGCCTCTACGGAATCGCAATAAACCCGAACCGGGTATTTAAGGTGAACACTAACGCTTATTATGAAATGTCTGGCTTGGAGGTATCTTTCGAAGAGCTCCGAACTTTCGGGGGGCATGACGCCAAGTTTATTGACTCTTTGCAGGAAAACGAATTCCGCCTCTATTACTATAATAAGTTTAAGGATATAGCGAGCACCTTGAATAAAGCCAAAAGTATTGTAGGGACTACGGCCAGCTTGCAGTACATGAAGAACGTTTTTAAAGAGAAATATTTGCTCTCCGAGGACACTAGCGGAAAGTTTAGCGTAGATAAGCTTAAATTTGATAAGCTGTACAAAATGTTGACCGAAATTTACACAGAGGATAACTTTGTTAAGTTTTTCAAAGTCCTTAATCGCAAAACTTATCTCAATTTTGACAAGGCCGTCTTTAAGATCAATATTGTTCCCAAAGTGAATTACACGATCTATGATGGCTTCAACTTGAGAAACACAAACTTGGCGGCCAATTTTAACGGGCAAAACACCGAGATTAACAACATGAATTTTACTAAGTTGAAGAATTTCACTGGACTCTTCGAATTCTACAAACTTCTCTGTGTTAGAGGAATAATCACGTCAAAATAGGCGGCCGCTTAATTAAGCTGCCTTCTGCGGGGCTTGCCTTCTGGCCATGCCCTTCTTCTCTCCCTTGCACCTGTACCTCTTGGTCTTTGAATAAAGCCTGAGTAGGAAGAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAASEQ ID NO: 26, DNA, artificial, light chain botulinum, human optimized from StrainUPI0000ED909ETCGAGCTCGGTACCTAATACGACTCACTATAAGGAGGAAATAAGAGAGAAAAGAAGAGTAAGAAGAAATATAAGAGCCACCATGCCCTTTGTTAATAAACAATTCAACTATAAGGATCCGGTCAATGGGGTTGACATCGCCTACATTAAAATCCCAAACGTGGGACAGATGCAACCTGTGAAAGCTTTTAAGATCCATAATAAAATCTGGGTCATTCCAGAGCGAGACACCTTTACGAATCCGGAAGAAGGAGATCTGAATCCACCACCCGAAGCAAAGCAAGTGCCGGTATCATACTATGACTCTACGTACCTCAGTACGGATAACGAGAAGGATAACTATCTGAAGGGTGTCACTAAGCTTTTCGAGAGGATCTATTCCACGGACCTTGGCCGGATGCTCCTCACATCAATCGTGCGCGGCATACCATTCTGGGGTGGGTCAACTATAGACACTGAGCTGAAAGTGATTGATACCAATTGTATCAATGTGATACAACCTGATGGCTCTTATCGGTCCGAAGAGCTTAATTTGGTGATTATAGGGCCTTCTGCGGATATTATTCAATTCGAGTGCAAGTCTTTCGGCCACGAGGTTCTCAATCTGACAAGAAACGGGTACGGAAGTACGCAATATATTCGGTTTAGTCCAGACTTCACCTTCGGTTTCGAGGAATCCCTCGAAGTTGACACAAACCCGTTGCTTGGTGCTGGCAAGTTCGCTACCGATCCGGCAGTGACTTTGGCGCACGAGCTGATCCACGCCGGTCATAGATTGTATGGCATAGCAATAAACCCTAATCGCGTTTTTAAAGTTAACACGAATGCCTACTACGAAATGTCAGGTTTGGAAGTTTCCTTCGAAGAGCTGAGAACCTTTGGCGGACATGACGCGAAGTTCATCGATAGTCTCCAAGAAAACGAGTTTAGATTGTATTATTACAACAAGTTTAAGGACATCGCCTCTACACTCAATAAGGCGAAATCAATCGTAGGAACGACAGCTTCACTGCAGTATATGAAGAATGTATTCAAAGAGAAATATCTTCTGTCAGAGGATACCAGCGGGAAATTCTCAGTGGATAAGCTCAAATTCGACAAACTGTATAAAATGTTGACCGAGATCTACACTGAAGATAACTTTGTCAAGTTCTTCAAGGTTTTGAACCGCAAGACTTATCTTAACTTTGATAAGGCCGTCTTTAAAATAAACATCGTGCCCAAGGTGAATTACACTATATACGACGGGTTCAATCTCCGCAATACGAATCTTGCTGCTAATTTCAACGGACAAAACACTGAGATTAACAACATGAACTTCACAAAGTTGAAGAATTTCACGGGATTGTTCGAATTTTATAAGCTTCTTTGTGTACGCGGTATTATAACATCAAAGTAAGCGGCCGCTTAATTAAGCTGCCTTCTGCGGGGCTTGCCTTCTGGCCATGCCCTTCTTCTCTCCCTTGCACCTGTACCTCTTGGTCTTTGAATAAAGCCTGAGTAGGAAGAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAASEQ ID NO: 27, DNA, artificial, light chain botulinum, human optimized from StrainUPI0000110A42TCGAGCTCGGTACCTAATACGACTCACTATAAGGAGGAAATAAGAGAGAAAAGAAGAGTAAGAAGAAATATAAGAGCCACCATGCCCTTCGTCAATAAACAATTCAATTATAAAGATCCGGTTAATGGTGTCGACATCGCGTATATCAAAATCCCGAATGTGGGCCAGATGCAGCCGGTTAAAGCTTTCAAAATACACAATAAAATATGGGTGATACCGGAGCGCGATACTTTCACCAATCCTGAAGAGGGCGACCTCAACCCGCCACCCGAGGCCAAGCAGGTACCCGTTAGCTATTACGACAGCACTTATTTGTCCACCGATAATGAGAAAGACAACTACCTGAAGGGCGTAACGAAGCTGTTCGAGCGAATCTACTCAACTGACTTGGGCCGCATGCTTCTCACAAGTATAGTTCGAGGAATTCCCTTCTGGGGAGGCTCAACGATTGACACTGAGCTGAAGGTGATAGATACAAATTGTATTAACGTGATTCAACCTGACGGCTCATACAGATCCGAAGAGTTGAACCTGGTTATCATCGGTCCATCAGCAGACATTATTCAATTCGAATGCAAAAGTTTCGGCCACGAGGTACTCAATCTTACGAGAAACGGTTACGGAAGCACTCAGTATATCAGGTTTTCTCCAGATTTCACCTTTGGTTTTGAAGAGAGCTTGGAAGTTGACACCAATCCTCTGCTGGGCGCCGGGAAGTTTGCGACGGACCCGGCTGTAACGCTCGCCCATGAGCTTATACATGCAGGTCACAGACTGTACGGCATAGCGATCAACCCCAACAGAGTGTTCAAGGTGAACACGAACGCATACTATGAGATGAGCGGACTCGAAGTTTCCTTCGAAGAGCTGCGAACCTTTGGCGGACACGACGCTAAATTCATTGATTCCTTGCAGGAGAATGAATTCAGATTGTATTATTATAACAAATTTAAGGACATCGCGTCAACTCTTAATAAGGCAAAGTCCATCGTTGGCACCACAGCATCCCTGCAATACATGAAAAACGTCTTCAAAGAGAAATATCTGCTCTCTGAGGATACATCCGGTAAGTTCTCCGTGGATAAATTGAAGTTCGACAAACTCTACAAAATGCTTACTGAGATTTATACAGAGGACAACTTTGTAAAATTTTTTAAAGTCTTGAACCGCAAGACTTACCTCAATTTCGATAAAGCGGTCTTTAAGATTAACATTGTCCCTAAAGTAAATTACACTATCTATGACGGTTTTAATTTGCGAAACACGAACCTCGCTGCCAATTTCAATGGACAAAACACAGAAATAAATAACATGAACTTCACCAAACTTAAAAACTTTACTGGACTGTTTGAGTTCTACAAGCTGTTGTGCGTGAGAGGAATAATCACGTCTAAATGAGCGGCCGCTTAATTAAGCTGCCTTCTGCGGGGCTTGCCTTCTGGCCATGCCCTTCTTCTCTCCCTTGCACCTGTACCTCTTGGTCTTTGAATAAAGCCTGAGTAGGAAGAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAASEQ ID NO: 28, DNA, artificial, light chain botulinum human optimized from Strain UPI000003409DTCGAGCTCGGTACCTAATACGACTCACTATAAGGAGGAAATAAGAGAGAAAAGAAGAGTAAGAAGAAATATAAGAGCCACCATGCAATTCGTTAATAAGCAGTTCAATTATAAGGATCCCGTAAACGGGGTGGATATAGCATATATTAAGATCCCGAATGTCGGTCAGATGCAGCCTGTTAAGGCGTTCAAGATTCACAACAAGATTTGGGTTATTCCCGAACGAGACACCTTTACAAACCCAGAGGAGGGGGACTTGAATCCGCCACCGGAAGCAAAACAGGTGCCCGTTTCTTACTATGATTCTACTTATCTTTCTACGGACAATGAGAAGGATAATTACCTGAAAGGTGTTACGAAACTGTTCGAGCGGATATATAGTACCGACTTGGGGCGCATGTTGCTCACCTCTATCGTACGAGGTATTCCTTTCTGGGGGGGCAGCACCATCGACACCGAACTCAAAGTCATCGACACAAATTGTATAAATGTAATACAACCAGACGGCAGTTATCGCTCAGAAGAGTTGAACCTGGTAATAATAGGTCCGTCCGCTGATATCATACAATTTGAATGCAAAAGTTTCGGCCATGAGGTCCTTAACCTTACCAGAAATGGGTACGGGTCCACGCAGTAC ATCAGGTTCAGTCCGGACTTCACCTTTGGGTTCGAGGAGTCCCTTGAAGTTGACACGAATCCACTGCTTGGTGCAGGTAAATTTGCTACAGATCCCGCTGTAACCCTCGCACACG AGCTCATACACGCCGGGCATCGACTTTACGGGATTGCGATCAACCCGAACAGAGTTTT CAAGGTAAATACGAATGCCTATTACGAAATGAGCGGGCTGGAGGTTTCTTTTGAGGA ACTGCGAACTTTTGGAGGCCATGATGCTAAATTCATTGACAGTCTCCAGGAGAATGAG TTCCGATTGTATTACTATAACAAGTTTAAAGATATTGCTAGTACCCTCAATAAGGCGAAGTCAATCGTCGGGACCACAGCGAGTTTGCAATATATGAAAAACGTGTTTAAAGAGAA ATACCTGCTGAGCGAGGATACATCCGGAAAATTTTCAGTAGATAAGTTGAAGTTCGAC AAACTTTATAAGATGCTTACTGAGATTTATACGGAGGATAACTTTGTTAAATTTTTCAA GGTACTTAACCGGAAGACCTACCTGAATTTTGATAAGGCTGTCTTTAAAATTAATATAG TGCCAAAGGTTAACTATACTATATACGATGGTTTCAATCTTAGAAACACTAATCTCGCCGCCAATTTCAATGGCCAAAATACGGAGATAAACAACATGAATTTCACTAAACTCAAAA ATTTTACTGGTCTGTTTGAGTTCTACAAGCTCCTGTGTGTGCGCGGGATTATCACATCA AAATAGGCGGCCGCTTAATTAAGCTGCCTTCTGCGGGGCTTGCCTTCTGGCCATGCCC TTCTTCTCTCCCTTGCACCTGTACCTCTTGGTCTTTGAATAAAGCCTGAGTAGGAAGA AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAASEQ ID NO: 29, PRT, Clostridium botulinum, light chain botulinum, UPI000003409DMQFVNKQFNYKDPVNGVDIAYIKIPNVGQMQPVKAFKIHNKIWVIPERDTFTNPEEGDL NPPPEAKQVPVSYYDSTYLSTDNEKDNYLKGVTKLFERIYSTDLGRMLLTSIVRGIPFWG GSTIDTELKVIDTNCINVIQPDGSYRSEELNLVIIGPSADIIQFECKSFGHEVLNLTRNGYGS TQYIRFSPDFTFGFEESLEVDTNPLLGAGKFATDPAVTLAHELIHAGHRLYGIAINPNRVFK VNTNAYYEMSGLEVSFEELRTFGGHDAKFIDSLQENEFRLYYYNKFKDIASTLNKAKSIVGTTASLQYMKNVFKEKYLLSEDTSGKFSVDKLKFDKLYKMLTEIYTEDNFVKFFKVLNR KTYLNFDKAVFKINIVPKVNYTIYDGFNLRNTNLAANFNGQNTEINNMNFTKLKNFTGL FEFYKLLCVRGIITSK*SEQ ID NO: 30, PRT, Clostridium botulinum, light chain botulinum, UPI0000110A42MPFVNKQFNYKDPVNGVDIAYIKIPNVGQMQPVKAFKIHNKIWVIPERDTFTNPEEGDL NPPPEAKQVPVSYYDSTYLSTDNEKDNYLKGVTKLFERIYSTDLGRMLLTSIVRGIPFWG GSTIDTELKVIDTNCINVIQPDGSYRSEELNLVIIGPSADIIQFECKSFGHEVLNLTRNGYGS TQYIRFSPDFTFGFEESLEVDTNPLLGAGKFATDPAVTLAHELIHAGHRLYGIAINPNRVFK VNTNAYYEMSGLEVSFEELRTFGGHDAKFIDSLQENEFRLYYYNKFKDIASTLNKAKSIVGTTASLQYMKNVFKEKYLLSEDTSGKFSVDKLKFDKLYKMLTEIYTEDNFVKFFKVLNR KTYLNFDKAVFKINIVPKVNYTIYDGFNLRNTNLAANFNGQNTEINNMNFTKLKNFTGL FEFYKLLCVRGIITSK*SEQ ID NO: 31, PRT, Clostridium botulinum, light chain botulinum, UPI0000ED909EMPFVNKQFNYKDPVNGVDIAYIKIPNVGQMQPVKAFKIHNKIWVIPERDTFTNPEEGDLNPPPEAKQVPVSYYDSTYLSTDNEKDNYLKGVTKLFERIYSTDLGRMLLTSIVRGIPFWGGSTIDTELKVIDTNCINVIQPDGSYRSEELNLVIIGPSADIIQFECKSFGHEVLNLTRNGYGSTQYIRFSPDFTFGFEESLEVDTNPLLGAGKFATDPAVTLAHELIHAGHRLYGIAINPNRVFKVNTNAYYEMSGLEVSFEELRTFGGHDAKFIDSLQENEFRLYYYNKFKDIASTLNKAKSIVGTTASLQYMKNVFKEKYLLSEDTSGKFSVDKLKFDKLYKMLTEIYTEDNFVKFFKVLNRKTYLNFDKAVFKINIVPKVNYTIYDGFNLRNTNLAANFNGQNTEINNMNFTKLKNFTGLFEFYKLLCVRGIITSK*SEQ ID NO: 32, PRT, Clostridium botulinum, light chain botulinum, UPI0000EF85BDMPFVNKQFNYKDPVNGVDIAYIKIPNVGQMQPVKAFKIHNKIWVIPERDTFTNPEEGDLNPPPEAKQVPVSYYDSTYLSTDNEKDNYLKGVTKLFERIYSTDLGRMLLTS1VRGIPFWG GSTIDTELKVIDTNCINVIQPDGSYRSEELNLVIIGPSADIIQFECKSFGHEVLNLTRNGYGS TQYIRFSPDFTFGFEESLEVDTNPLLGAGKFATDPAVTLAHELIHAGHRLYGIAINPNRVFK VNTNAYYEMSGLEVSFEELRTFGGHDAKFIDSLQENEFRLYYYNKFKDIASTLNKAKSIVGTTASLQYMKNVFKEKYLLSEDTSGKFSVDKLKFDKLYKMLTEIYTEDNFVKFFKVLNR KTYLNFDKAVFKINIVPKVNYTIYDGFNLRNTNLAANFNGQNTEINNMNFTKLKNFTGL FEFYKLLCVRGIITSK*SEQ ID NO: 33, PRT, Clostridium botulinum, light chain botulinum, UPI00016529B7MPFVNKQFNYKDPVNGVDIAYIKIPNVGQMQPVKAFKIHNKIWVIPERDTFTNPEEGDL NPPPEAKQVPVSYYDSTYLSTDNEKDNYLKGVTKLFERIYSTDLGRMLLTSIVRGIPFWG GSTIDTELKVIDTNCINVIQPDGSYRSEELNLVIIGPSADIIQFECKSFGHEVLNLTRNGYGS TQYIRFSPDFTFGFEESLEVDTNPLLGAGKFATDPAVTLAHELIHAGHRLYGIAINPNRVFK VNTNAYYEMSGLEVSFEELRTFGGHDAKFIDSLQENEFRLYYYNKFKDIASTLNKAKSIV GTTASLQYMKNVFKEKYLLSEDTSGKFSVDKLKFDKLYKMLTEIYTEDNFVKFFKVLNR KTYLNFDKAVFKINIVPKVNYTIYDGFNLRNTNLAANFNGQNTEINNMNFTKLKNFTGLFEFYKLLCVRGIITSK*SEQ ID NO: 34, PRT, Clostridium botulinum, light chain botulinum, UPI0001 A954C8MPFVNKQFNYKDPVNGVDIAYIKIPNAGQMQPVKAFKIHNKIWVIPERDTFTNPEEGDL NPPPEAKQVPVSYYDSTYLSTDNEKDNYLKGVTKLFERIYSTDLGRMLLTSIVRGIPFWG GSTIDTELKV1DTNCINVIQPDGSYRSEELNLVI1GPSAD1IQFECKSFGHEVLNLTRNGYGS TQYIRFSPDFTFGFEESLEVDTNPLLGAGKFATDPAVTLAHELIHAGHRLYGIAINPNRVFK VNTNAYYEMSGLEVSFEELRTFGGHDAKFIDSLQENEFRLYYYNKFKDIASTLNKAKSIVGTTASLQYMKNVFKEKYLLSEDTSGKFSVDKLKFDKLYKMLTEIYTEDNFVKFFKVLNR KTYLNFDKAVFKINIVPKVNYTIYDGFNLRNTNLAANFNGQNTEINNMNFTKLKNFTGL FEFYKLLCVRGIITSK*SEQ ID NO: 35, PRT, Clostridium botulinum, light chain botulinum, UPI00027EE164MPFVNKQFNYKDPVNGVDIAYIKIPNAGQMQPVKAFKIHNKIWVIPERDTFTNPEEGDLNPPPEAKQVPVSYYDSTYLSTDNEKDNYLKGVTKLFERIYSTDLGRMLLTSIVRGIPFWG GSTIDTELKVIDTNCINVIQPDGSYRSEELNLVIIGPSADIIQFECKSFGHEVLNLTRNGYGS TQYIRFSPDFTFGFEESLEVDTNPLLGAGKFATDPAVTLAHELIHAGHRLYGIAINPNRVFK VNTNAYYEMSGLEVSFEELRTFGGHDAKFIDSLQENEFRLYYYNKFKDIASTLNKAKSIVGTTASLQYMKNVFKEKYLLSEDTSGKFSVDKLKFDKLYKMLTEIYTEDNFVKFFKVLNR KTYLNFDKAVFKINIVPKVNYTIYDGFNLRNTNLAANFNGQNTEINNMNFTKLKNFTGL FEFYKLLCVRGIITSK*SEQ ID NO: 36, PRT, Clostridium botulinum, light chain botulinum, UPI000016EA88MPFVNKQFNYKDPVNGVDIAYIKIPNAGQMQPVKAFKIHNKIWVIPERDTFTNPEEGDL NPPPEAKQVPVSYYDSTYLSTDNEKDNYLKGVTKLFERIYSTDLGRMLLTSIVRGIPFWG GSTZDTELKVIDTNCINVIQPDGSYRSEELNLVIIGPSADIIQFECKSFGHDVLNLTRNGYGS TQYIRFSPDFTFGFEESLEVDTNPLLGAGKFATDPAVTLAHELIHAEHRLYGIAINPNRVFK VNTNAYYEMSGLEVSFEELRTFGGHDAKFIDSLQENEFRLYYYNKFKDVASTLNKAKSI1 GTTASLQYMKNVFKEKYLLSEDTSGKFSVDKLKFDKLYKMLTEIYTEDNFVNFFKVINR KTYLNFDKAVFRINIVPDENYTIKDGFNLKGANLSTNFNGQNTEINSRNFTRLKNFTGLFEFYKLLCVRGIIPFK*SEQ ID NO: 37, PRT, Clostridium botulinum, light chain botulinum, UPI000067C53EMPFVNKQFNYKDPVNGVDIAYIKIPNAGQMQPVKAFKIHNKIWVIPERDTFTNPEEGDL NPPPEAKQVPVSYYDSTYLSTDNEKDNYLKGVTKLFERIYSTDLGRMLLTSIVRGIPFWG GSTIDTELKVIDTNCINVIQPDGSYRSEELNLVIIGPSADIIQFECKSFGHDVLNLTRNGYGS TQYIRFSPDFTFGFEESLEVDTNPLLGAGKFATDPAVTLAHELIHAEHRLYGIAINPNRVFK VNTNAYYEMSGLEVSFEELRTFGGHDAKFIDSLQENEFRLYYYNKFKDVASTLNKAKSII GTTASLQYMKNVFKEKYLLSEDTSGKFSVDKLKFDKLYKMLTEIYTEDNFVNFFKVINR KTYLNFDKAVFRINIVPDENYTIKDGFNLKGANLSINFNGQNTEINSRNFTRLKNFTGLFEFYKLLCVRGIIPFK*SEQ ID NO: 38, PRT, Clostridium botulinum, light chain botulinum, UPI0000EF84BDMPFVNKQFNYKDPVNGVDIAYIKIPNAGQMQPVKAFKIHNKIWVIPERDTFTNPEEGDL NPPPEAKQVPVSYYDSTYLSTDNEKDNYLKGVTKLFERIYSTDLGRMLLTSIVRGIPFWGGSTZDTELKVIDTNCINVIQPDGSYRSEELNLVIIGPSADIIQFECKSFGHDVLNLTRNGYGS TQYIRFSPDFTFGFEESLEVDTNPLLGAGKFATDPAVTLAHELIHAEHRLYGIAINPNRVFK VNTNAYYEMSGLEVSFEELRTFGGHDAKFIDSLQENEFRLYYYNKFKDVASTLNKAKSII GTTASLQYMKNVFKEKYLLSEDTSGKFSVDKLKFDKLYKMLTEIYTEDNFVNFFKVINRKTYLNFDKAVFRINIVPDENYTIKDGFNLKGANLSTNFNGQNTEINSRNFTRLKNFTGLFEFYKLLCVRGIIPFK*SEQ ID NO: 39, PRT, Clostridium botulinum, light chain botulinum UPI0001C0B376MPFVNKQFNYKDPVNGVDIAYIKIPNAGQMQPVKAFKIHNKIWVIPERDTFTNPEEGDL NPPPEAKQVPVSYYDSTYLSTDNEKDNYLKGVTKLFERIYSTDLGRMLLTSIVRGIPFWG GSTIDTELKVIDTNCINVIQPDGSYRSEELNLVIIGPSADIIQFECKSFGHDVLNLTRNGYGS TQYIRFSPDFTFGFEESLEVDTNPLLGAGKFATDPAVTLAHELIHAEHRLYGIAINPNRVFK VNTNAYYEMSGLEVSFEELRTFGGHDAKFIDSLQENEFRLYYYNKFKDVASTLNKAKSII GTTASLQYMKNVFKEKYLLSEDTSGKFSVDKLKFDKLYKMLTEIYTEDNFINFFKVINRK TYLNFDKAVFRINIVPDENYTIKDGFNLKGANLSTNFNGQNTEINSRNFTRLKNFTGLFEFYKLLCVRGIIPFK*SEQ ID NO: 40, PRT, Clostridium botulinum, light chain botulinum, UPI0001C32E84MPFVNKQFNYKDPVNGVDIAYIKIPNAGQMQPVKAFKIHNKIWVIPERDTFTNPEEGDL NPPPEAKQVPVSYYDSTYLSTDNEKDNYLKGVTKLFERIYSTDLGRMLLTSIVRGIPFWG GSTIDTELKVIDTNCINVIQPDGSYRSEELNLVIIGPSADIIQFECKSFGHDVLNLTRNGYGS TQYIRFSPDFTFGFEESLEVDTNPLLGAGKFATDPAVTLAHELIHAEHRLYGIAINPNRVFK VNTNAYYEMSGLEVSFEELRTFGGHDAKFIDSLQENEFRLYYYNKFKDVASTLNKAKSII GTTASLQYMKNVFKEKYLLSEDTSGKFSVDKLKFDKLYKMLTEIYTEDNFVNFFKVINR KTYLNFDKAVFRINIVPDENYTIKDGFNLKGANLSTNFNGQNTEINSRNFTRLKNFTGLFEFYKLLCVRGIIPFK*SEQ ID NO: 41, PRT, Clostridium botulinum, light chain botulinumUPI0001F3B30DMPFVNKQFNYKDPVNGVDIAYIKIPNAGQMQPVKAFKIHNKIWVIPERDTFTNPEEGDL NPPPEAKQVPVSYYDSTYLSTDNEKDNYLKGVTKLFERIYSTDLGRMLLTSIVRGIPFWG GSTZDTELKVIDTNCINVIQPDGSYRSEELNLVIIGPSADIIQFECKSFGHDVLNLTRNGYGS TQYIRFSPDFTFGFEESLEVDTNPLLGAGEFATDPAVTLAHELIHAEHRLYGIAINPNRVFK VNTNAYYEMSGLEVSFEELRTFGGHDAKFIDSLQENEFRLYYYNKFKDVASTLNKAKSII GTTASLQYMKNVFKEKYLLSEDTSGKFSVDKLKFDKLYKMLTEIYTEDNFVNFFKVINR KTYLNFDKAVFRINIVPDENYTIKDGFNLKGANLSTNFNGQNTEINSRNFTRLKNFTGLFEFYKLLCVRGIIPFK*SEQ ID NO: 42, PRT, Clostridium botulinum, light chain botulinumUPI000290BDD5MPFVNKQFNYKDPVNGVDIAYIKIPNAGQMQPVKAFKIHNKIWVIPERDTFTNPEEGDL NPPPEAKQVPVSYYDSTYLSTDNEKDNYLKGVTKLFERIYSTDLGRMLLTSIVRGIPFWG GSTZDTELKVIDTNCINVIQPDGSYRSEELNLVIIGPSADIIQFECKSFGHDVLNLTRNGYGS TQYIRFSPDFTFGFEESLEVDTNPLLGAGKFATDPAVTLAHELIHAEHRLYGIAINPNRVFKVNTNAYYEMSGLEVSFEELRTFGGHDAKFIDSLQENEFRLYYYNKFKDVASTLNKAKSII GTTASLQYMKNVFKEKYLLSEDTSGKFSVDKLKFDKLYKMLTEIYTEDNFVNFFKVINR KTYLNFDKAVFRINIVPDENYTIKDGFNLKGANLSINFNGQNTEINSRNFTRLKNFTGLFE FYKLLCVRGIIPFK*SEQ ID NO: 43, PRT, Clostridium botulinum, light chain botulinumUPI000290BEB 1MPFVNKQFNYKDPVNGVDIAYIKIPNAGQMQPVKAFKIHNKIWVIPERDTFTNPEEGDL NPPPEAKQVPVSYYDSTYLSTDNEKDNYLKGVTKLFERIYLTDLGRMLLTSIVRGIPFWG GSTIDTELKVIDTNCINVIQPDGSYRSEELNLVIIGPSADIIQFECKSFGHDVLNLTRNGYGS TQYIRFSPDFTFGFEESLEVDTNPLLGAGKFATDPAVTLAHELIHAEHRLYGIAINPNRVFK VNTNAYYEMSGLEVSFEELRTFGGHDAKFIDSLQENEFRLYYYNKFKDVASTLNKAKSI1 GTTASLQYMKNVFKEKYLLSEDTSGKFSVDKLKFDKLYKMLTEIYTEDNFVNFFKVINR KTYLNFDKAVFRINIVPDENYTIKDGFNLKGANLSTNFNGQNTEINSRNFTRLKNFTGLFEFYKLLCVRGIIPFK*SEQ ID NO: 44, PRT, Clostridium botulinum, light chain botulinumUPI0004A59983MPFVNKQFNYKDPVNGVDIAYIKIPNAGQMQPVKAFKIHNKIWVIPERDTFTNPEEGDL NPPPEAKQVPVSYYDSTYLSTDNEKDNYLKGVTKLFERIYSTDLGRMLLTSIVRGIPFWG GSTZDTELKVIDTNCINVIQPDGSYRSEELNLVIIGPSADIIQFECKSFGHDVLNLTRNGYGS TQYIRFSPDFTFGFEESLEVDTNPLLGAGKFATDPAVTLAHELIHAEHRLYGIAINPNRVFK VNTNAYYEMSGLEVSFEELRTFGGHDAKFIDSLQENEFRLYYYNKFKDVASTLNKAKSII GTTASLQYMKNVFKEKYLLSEDTSGKFSVDKLKFDKLYKMLTEIYTEDNFVNFFKVINR KTYLNFDKAVFRINIVPDENYTIKDGFNLKGANLSTNFNGQNTEINSRNFTRLKNFTGLFEFYKLLCVRGIIPFK*SEQ ID NO: 45, PRT, Clostridium botulinum, light chain botulinumUPI00005B712CMPFVNKPFNYRDPGNGVDIAYIKIPNAGQMQPVKAFKIHEGVWVIPERDTFTNPEEGDL NPPPEAKQVPVSYYDSTYLSTDNEKDNYLKGVIKLFDRIYSTGLGRMLLSFIVKGIPFWG GSTIDTELKVIDTNCINVIEPGGSYRSEELNLVITGPSADIIQFECKSFGHDVFNLTRNGYGS TQYIRFSPDFTFGFEESLEVDTNPLLGAGTFATDPAVTLAHELIHAAHRLYGIAINPNRVLK VKTNAYYEMSGLEVSFEELRTFGGNDTNFIDSLWQKKFSRDAYDNLQNIARILNEAKTIV GTTTPLQYMKNIFIRKYFLSEDASGKISVNKAAFKEFYRVLTRGFTELEFVNPFKVINRKT YLNFDKAVFRINIVPDENYTINEGFNLEGANSNGQNTEINSRNFTRLKNFTGLFEFYKLLCVRGIIPFK*SEQ ID NO: 46, PRT, Clostridium botulinum, light chain botulinumUPI00016DBC11MPFVNKQFNYRDPVNGVDIAYIKIPNAGQMQPVKAFKIHEGVWVIPERDTFTNPEEGDL NPPPEAKQVPVSYYDSTYLSTDNEKDNYLKGVIKLFDRIYSTGLGRMLLSFIVKGIPFWG GSTIDTELKVIDTNCINVIEPGGSYRSEELNLVITGPSADIIQFECKSFGHDVFNLTRNGYGSTQYIRFSPDFTFGFEESLEVDTNPLLGAGTFATDPAVTLAHELIHAAHRLYGIAINPNRVLK VKTNAYYEMSGLEVSFEELRTFGGNDTNFIDSLWQKKFSRDAYDNLQNIARILNEAKTIV GTTTPLQYMKNIFLRKYFLSEDASGKISVNKAAFKEFYRVLTRGFTELEFVNPFKVINRKT YLNFDKAVFRINIVPDENYTINEGFNLEGANSNGQNTEINSRNFTRLKNFTGLFEFYKLLC VRGIIPFK*SEQ ID NO: 47, PRT, Clostridium botulinum, light chain botulinumUPI000290C3D0MPFVNKQFNYRDPVNGVDIAYIKIPNAGQMQPVKAFKIHEGVWVIPERDTFTNPEEGDLNPPPEAKQVPVSYYDSTYLSTDNEKDNYLKGVIKLFDRIYSTGLGRMLLSFIVKGIPFWG GSTIDTELKVIDTNCINVIEPGGSYRSEELNLVITGPSADIIQFECKSFGHDVFNLTRNGYGS TQYIRFSPDFTFGFEESLEVDTNPLLGAGTFATDPAVTLAHELIHAAHRLYGIAINPNRVLK VKTNAYYEMSGLEVSFEELRTFGGNDTNFIDSLWQKKFSRDAYDNLQNIARILNEAKTIVGTTTPLQYMKNIFLRKYFLSEDASGKISVNKPAFKEFYRVLTRGFTELEFVNPFKVINRKT YLNFDKAVFRINIVPDENYTINEGFNLEGANSNGQNTEINSRNFTRLKNFTGLFEFYKLLC VRGIIPFK*SEQ ID NO: 48, PRT, Clostridium botulinum, light chain botulinumUPI00005B712DMPLVNQQINYYDPVNGVDIAYII<IPNAGI<MQPVI<AFKIHNKVWVIPERDIFTNPEEVDLNPPPEAKQVPISYYDSAYLSTDNEKDNYLKGVIKLFERIYSTDLGRMLLISIVRGIPFWGGG KIDTELKVIDTNCINIIQLDDSYRSEELNLAIIGPSANIIESQCSSFRDDVLNLTRNGYGSTQ YIRFSPDFTVGFEESLEVDTNPLLGAGKFAQDPAVALAHELIHAEHRLYGIAINTNRVFKV NTNAYYEMAGLEVSLEELITFGGNDAKFIDSLQKKEFSLYYYNKFKDIASTLNKAKSIVGTTASLQYMKNVFKEKYLLSEDATGKFLVDRLKFDELYKLLTEIYTEDNFVKFFKVLNRKT YLNFDKAVFKINIVPDVNYTIHDGFNLRNTNLAANFNGQNIEINNKNFDKLKNFTGLFEF YKLLCVRGIITSK*SEQ ID NO: 49, PRT, Clostridium botulinum, light chain botulinumUPI00019DB885MPFVNKQFNYNDPENGVDIAYIKIPNAGKMQPVKAFKIHNKVWVIPERDIFTNPEEVDLNPPPEAKQVPISYYDSAYLSTDNEKDNYLKGVIKLFERIYSTDLGRMLLISIVRGIPFWGG GKIDTELKVIDTNCINIIQLDDSYRSEELNLAI1GPSAN1IESQCSSFRDDVLNLTRNGYGST QYIRFSPDFTVGFEESLEVDTNPLLGAGKFAQDPAVALAHELIHAEHRLYGIAINTNRVFK VNTNAYYEMAGLEVSLEELITFGGNDAKFIDSLQKKEFSLYYYNKFKDIASTLNKAKSIVGTTASLQYMKNVFKEKYLLSEDATGKFLVDRLKFDELYKLLTEIYTEDNFVKFFKVLNR KTYLNFDKAVFKINIVPDVNYTIHDGFNLRNTNLAANFNGQNIEINNKNFDKLKNFTGLF EFYKLLCVRGIITSK*SEQ ID NO: 50, PRT, Clostridium botulinum, light chain botulinumUPI000198BDAEMLFVNKQFNYKDPVNGVDIAYIKIPNAGQMQPVKAFKIHNKIWVIPERDTFTNPEEGDL NPPPEAKQVPVSYYDSTYLSTDNEKDNYLKGVTKLFERIYSTELGRMLLTSIVRGIPFWGGSTIDTELKVIDTNCINVIQPDGSYRSEELNLVIIGPSADIIQFECKSFGHDVLNLTRNGYGS TQYIRFSPDFTFGFEESLEVDTNPLLGAGKFATDPAVTLAHELIHAGHRLYGIAINPNRVFK VNTNAYYEMSGLEVSFEELRTFGEHDAKFIDSLQENEFRLYYYNKFKDIASTLNKAKSIV GTTASLQYMKNVFKEKYLLSEDTSGKFSVDKLKFDKLYKMLTEIYTEDNFVKFFKVLNR KTYLNFDKAVFKINIVPEVNYTIYDGFNLRNTNLAANFNGQNTEINNMNFTKLKNFTGLF EFYKLLCVRGIITSK*SEQ ID NO: 51, PRT, Clostridium botulinum, light chain botulinum UPI0001AE7D6AMPFVNKQFNYKDPVNGVDIAYIKIPNAGQMQPVKAFKIHNKIWVIPERDTFTNPEEGDL NPPPEAKQVPVSYYDSTYLSTDNEKDNYLKGVTKLFERIYSTELGRMLLTSIVRGIPFWG GST1DTELKV1DTNCINVIQPDGSYRSEELNLVI1GPSAD1IQFECKSFGHDVLNLTRNGYGS TQYIRFSPDFTFGFEESLEVDTNPLLGAGKFATDPAVTLAHELIHAGHRLYGIAINPNRVFK VNTNAYYEMSGLEVSFEELRTFGEHDAKFIDSLQENEFRLYYYNKFKDIASTLNKAKSIV GTTASLQYMKNVFKEKYLLSEDTSGKFSVDKLKFDKLYKMLTEIYTEDNFVKFFKVLNR KTYLNFDKAVFKINIVPEVNYTIYDGFNLRNTNLAANFNGQNTEINNMNFTKLKNFTGLF EFYKLLCVRGIITSK*SEQ ID NO: 52, PRT, Clostridium botulinum, light chain botulinumUPI0001B7D251MPFVNKQFNYKDPVNGVDIAYIKIPNAGQMQPVKAFKIHNKIWVIPERDTFTNPEEGDL NPPPEAKQVPVSYYDSTYLSTDNEKDNYLKGVTKLFERIYSTDLGRMLLTSIVRGIPFWG GSTIDTELKVIDTNCINVIQPDGSYRSEELNLVIIGPSADIIQFECKSFGHEVLNLTRNGYGS TQYIRFSPDFTFGFEESLEVDTNPLLGAGKFATDPAVTLAHELIHAGHRLYGIAINPNRVFK VNTNAYYEMSGLEVSFEELRTFGGHDAKFIDSLQENEFRLYYYNKFKDIASTLNKAKSIV GTTASLQYMKNVFKEKYLLSEDTSGKFSVDKLKFDKLYKMLTEIYTEDNFVKFFKVLNR KTYLNFDI<AVFKINIVPI<VNYTIYDGFNLRNTNLAANFNGQNTEINNMNFAI<LKNFTGL FEFYKLLCVRGIITSK*SEQ ID NO: 53, PRT, Clostridium botulinum, light chain botulinumUPI000290B995MPFVNKQFNYKDPVNGVDIAYIKIPNAGQMQPVKAFKIHNKIWVIPERDIFTNPEEGDLN PPPEAKQVPVSYYDSTYLSTDNEKDNYLKGVTKLFER1YSTDLGRMLLTSIVRGIPFWGG STZDTELKVIDTNCINVIQPDGSYRSEELNLVIIGPSADIINFECKSFGHDVLNLTRNGYGST QYIRFSPDFTFGFEESLEVDTNPLLGAGKFAIDPAVTLAHELIHAGHRLYGIAINPNRVFKV NTNAYYEMSGLEVSFEELRTFGGHDAKFIDSLQENEFRLYYYNKFKEVASILNKAKSIIGT TASLQYMKNVFKEKYLLSEDTSGKFSVDKLRFDKLYKMLTEIYTEDNFVKFFKVLNRKT YLNFDKAVFKMNIVPEVNYTIYDGFNLRNTNLAANFNGQNTEINNMNFTKLKNFTGLFE FYKLLCVRGIITSK*SEQ ID NO: 54, PRT, Clostridium botulinum, light chain botulinum UPI0003C9D2A1MPFVNKQFNYKDTVNGVDIAYIKIPNAGQMQPVKAFKIHNKIWVIPERDTFTNPKEGDL NPPPEAKQVPVSYYDSTYLSTDNEKDNYLKGVTKLFERIYSTDLGRMLLTSIVRGIPFWG GSTIDTELKVIDTNCINVIQPDGSYRSEELNLVIIGPSADIIQFECKSFGHDVLNLTRNGYGS TQYIRFSPDFTFGFEESLEVDTNPLLGAGKFATDPAVTLAHELIHAEHRLYGIAINPNRVFK VNTNAYYEMSGLEVSFEELRTFGGHNAKFIDSLQENEFRLYYYNKFKDIASTLNKAKSIV GTTASLQYMKNVFKEKYLLSEDTSGKFSVDKLKFDKLYKMLTEIYTEDNFVKFFKVLNR KTYLNFDKAVFKINIVPDENYTIKDGFNLKNTNLAANFNGQNTEINSRNFTKLKNFTGLF EFYKLLCVRGIIPFK*SEQ ID NO: 55, PRT, Clostridium botulinum, light chain botulinum UPI000559A469MPFVNKQFNYKDTVNGIDIAYIKIPNAGQMQPVKAFKIHNKIWVIPERDTFTNPKEGDLN PPPEAKQVPVSYYDSTYLSTDNEKDNYLKGVTKLFERIYSTDLGRMLLTSIVRGIPFWGG STIDTELKVIDTNCINVIQPDGSYRSEELNLVIIGPSADIIQFECKSFGHDVLNLTRNGYGST QYIRFSPDFTFGFEESLEVDTNPLLGAGKFATDPAVTLAHELIHAEHRLYGIAINPNRVFKV NTNAYYEMSGLEVSFEELRTFGGHNAKFIDSLQENEFRLYYYNKFKDIASTLNKAKSIVG TTASLQYMKNVFKEKYLLSEDTSGKFSVDKLKFDKLYKMLTEIYTEDNFVKFFKVLNRK TYLNFDKAVFKINIVPDENYTIKDGFNLKNTNLAANFNGQNTEINSRNFTKLKNFTGLFE FYKLLCVRGIIPFK*SEQ ID NO: 56, PRT, Clostridium botulinum, light chain botulinum UPI0000001386MPFVNKQFNYKDPVNGVDIAYIKIPNAGQMQPVKAFKIHNKIWVIPERDTFTNPEEGDL NPPPEAKQVPVSYYDSTYLSTDNEKDNYLKGVTKLFERIYSTDLGRMLLTSIVRGIPFWG GSTIDTELKVIDTNCINVIQPDGSYRSEELNLVIIGPSADIIQFECKSFGHEVLNLTRNGYGS TQYIRFSPDFTFGFEESLEVDTNPLLGAGKFATDPAVTLAHELIHAGHRLYGIAINPNRVFK VNTNAYYEMSGLEVSFEELRTFGGHDAKFIDSLQENEFRLYYYNKFKDIASTLNKAKSIV GTTASLQYMKNVFKEKYLLSEDTSGKFSVDKLKFDKLYKMLTEIYTEDNFVKFFKVLNR KTYLNFDKAVFKINIVPKVNYTIYDGFNLRNTNLAANFNGQNTEINNMNFTKLKNFTGL FEFYKLLCVRGIITSK*SEQ ID NO: 57, PRT, Clostridium botulinum, heavy chain botulinum UPI000003409DMTKSLDKGYNKALNDLCIKVNNWDLFFSPSEDNFTNDLNKGEEITSDTNIEAAEENISLD LIQQ YYLTFNFDNEPENISIENL S SDIIGQLELMPNIERFPNGKKYELDKYTMFHYLRAQEF EHGKSRIALTNSVNEALLNPSRVYTFFSSDYVKKVNKATEAAMFLGWVEQLVYDFTDET SEVSTTDKIADITIIIPYIGPALNIGNMLYKDDFVGALIFSGAVILLEFIPEIAIPVLGTFALVS YIANKVLTVQTIDNALSKRNEKWDEVYKYIVTNWLAKVNTQIDLIRKKMKEALENQAE ATKAIINYQYNQYTEEEKNNINFNIDDLS SKLNESINK AM ININKFLNQC S VS YLMNSMIP YGVKRLEDFDASLKDALLKYIYDNRGTLIGQVDRLKDKVNNTLSTDIPFQLSKYVDNQR LLSTFTEYIKNIINTSILNLRYESNHLIDLSRYASKINIGSKVNFDPIDKNQIQLFNLESSKIE VILKNAIVYNSMYENFSTSFWIRIPKYFNSISLNNEYTIINCMENNSGWKVSLNYGEIIWT LQDTQEIKQRVVFKYSQMINISDYINRWIFVTITNNRLNNSKIYINGRLIDQKPISNLGNIHASNNIMFKLDGCRDTHRYIWIKYFNLFDKELNEKEIKDLYDNQSNSGILKDFWGDYLQYDKPYYMLNLYDPNKYVDVNNVGIRGYMYLKGPRGSVMTTNIYLNSSLYRGTKFIIKKYASGNKDNIVRNNDRVYINVVVKNKEYRLATNASQAGVEKILSALEIPDVGNLSQVVVMKSKNDQGITNKCKMNLQDNNGNDIGFIGFHQFNNIAKLVASNWYNRQIERSSRTLGCSWEFIPVDDGWGERPL*SEQ ID NO: 58, PRT, Clostridium botulinum, heavy chain botulinum, UPI0000110A42MTKSLDKGYNKALNDLCIKVNNWDLFFSPSEDNFTNDLNKGEEITSDTNIEAAEENISLD LIQQ YYLTFNFDNEPENISIENL S SDIIGQLELMPNIERFPNGKKYELDKYTMFHYLRAQEF EHGKSRIALTNSVNEALLNPSRVYTFFSSDYVKKVNKATEAAMFLGWVEQLVYDFTDET SEVSTTDKIADITIIIPYIGPALNIGNMLYKDDFVGALIFSGAVILLEFIPEIAIPVLGTFALVS YIANKVLTVQTIDNALSKRNEKWDEVYKYIVTNWLAKVNTQIDLIRKKMKEALENQAE ATKAIINYQYNQYTEEEKNNINFNIDDLS KLNESINK AM ININKFLNQC S VS YLMNSMIP YGVKRLEDFDASLKDALLKYIYDNRGTLIGQVDRLKDKVNNTLSTDIPFQLSKYVDNQR LLSTFTEYIKNIINTSILNLRYESNHLIDLSRYASKINIGSKVNFDPIDKNQIQLFNLESSKIE VILKNAIVYNSMYENFSTSFWIRIPKYFNSISLNNEYTIINCMENNSGWKVSLNYGEIIWT LQDTQE1KQRVVFKYSQM1NISDYINRWIFVTITNNRLNNSK1YINGRLIDQKPISNLGNIH ASNNIMFKLDGCRDTHRYIWIKYFNLFDKELNEKEIKDLYDNQSNSGILKDFWGDYLQYDKPYYMLNLYDPNKYVDVNNVGIRGYMYLKGPRGSVMTTNIYLNSSLYRGTKFIIKKY ASGNKDNIVRNNDRVYINVVVKNKEYRLATNASQAGVEKILSALEIPDVGNLSQVVVM KSKNDQGITNKCKMNLQDNNGNDIGFIGFHQFNNIAKLVASNWYNRQIERSSRTLGCSW EFIPVDDGWGERPL*SEQ ID NO: 59, PRT, Clostridium botulinum, heavy chain botulinum, UPI0000ED909EMTK SLDKGYNK ALNDLC IK VNNWDLFF SP SEDNF TNDLNKGEEIT SDTNIE AAEENI SLD LIQQ YYLTFNFDNEPENISIENL S SDIIGQLELMPNIERFPNGKKYELDK YTMFHYLRAQEF EHGKSRIALTNSVNEALLNPSRVYTFFSSDYVKKVNKATEAAMFLGWVEQLVYDFTDET SEVSTTDKIADITIIIPYIGPALNIGNMLYKDDFVGALIFSGAVILLEFIPEIAIPVLGTFALVS YIANKVLTVQTIDNALSKRNEKWDEVYKYIVTNWLAKVNTQIDLIRKKMKEALENQAE ATKAIINYQYNQYTEEEKNNINFNIDDLSSKLNESINKAMININKFLNQCSVSYLMNSMIP YGVKRLEDFDASLKDALLKYIYDNRGTLIGQVDRLKDKVNNTLSTDIPFQLSKYVDNQR LLSTFTEYIKNIINTSILNLRYESNHLIDLSRYASKINIGSKVNFDPIDKNQIQLFNLESSKIE VILKNAIVYNSMYENFSTSFWIRIPKYFNSISLNNEYTIINCMENNSGWKVSLNYGEIIWT LQDTQEIKQRVVFKYSQMINISDYINRWIFVTITNNRLNNSKIYINGRLIDQKPISNLGNIH ASNNIMFKLDGCRDTHRYIWIKYFNLFDKELNEKEIKDLYDNQSNSGILKDFWGDYLQY DKPYYMLNLYDPNKYVDVNNVGIRGYMYLKGPRGSVMTTNIYLNSSLYRGTKFIIKKY ASGNKDNIVRNNDRVYINVVVKNKEYRLATNASQAGVEKILSALEIPDVGNLSQVVVM KSKNDQGITNKCKMNLQDNNGNDIGFIGFHQFNNIAKLVASNWYNRQIERS SRTLGC SW EFIPVDDGWGERPL*SEQ ID NO: 60, PRT, Clostridium botulinum, heavy chain botulinum UPI0000EF85BDMTKSLDKGYNKALNDLCIKVNNWDLFFSPSEDNFTNDLNKGEEITSDTNIEAAEENISLD LIQQ YYLTFNFDNEPENISIENL S SDIIGQLELMPNIERFPNGEKYELDKYTMFHYLRAQEF EHGKSRIALTNSVNEALLNPSRVYTFFSSDYVKKVNKATEAAMFLGWVEQLVYDFTDET SEVSTTDKIADITIIIPYIGPALNIGNMLYKDDFVGALIFSGAVILLEFIPEIAIPVLGTFALVS YIANKVLTVQTIDNALSKRNEKWDEVYKYIVTNWLAKVNTQIDLIRKKMKEALENQAE ATKAIINYQYNQYTEEEKNNINFNIDDLS SKENE SINK AM IN INKFLNQC S VS YLMNSMIP YGVKRLEDFDASLKD ALLKYI YDNRGTLIGQVDRLKDKVNNTLSTDIPFQLSKYVDNQR LLSTFTEYIKNIINTSILNLRYESNHLIDLSRYASK1NIGSKVNFDPIDKNQIQLFNLESSKIE VILKNAIVYNSMYENFSTSFWIRIPKYFNSISLNNEYTIINCMENNSGWKVSLNYGEIIWT LQDTQEIKQRVVFKYSQMINISDYINRWIFVTITNNRLNNSKIYINGRLIDQKPISNLGNIH ASNNIMFKLDGCRDTHRYIWIKYFNLFDKELNEKEIKDLYDNQSNSGILKDFWGDYLQY DKPYYMLNLYDPNKYIDVNNVGIRGYMYLKGPRGNVMTTNIYLNSSLYMGTKFIIKKY ASGNKDNIVRNNDRVYINVWKNKEYRLATNASQAGVEKILSALEIPDVGNLSQVVVM KSKNDQGITNKCKMNLQDNNGNDIGFIGFHQFNNIAKLVASNWYNRQIERSSRTLGCSW EFIPVDDGWGERPL*SEQ ID NO: 61, PRT, Clostridium botulinum, heavy chain botulinum UPI00016529B7MTKSLDKGYNKALNDLCIKVNNWDLFFSPSEDNFTNDLNKGEEITSDTNIEAAEENISLD LIQQ YYLTFNFDNEPENISIENL S SDIIGQLELMPNIERFPNGKKYELDK YTMFHYLRAQEF EHGKSRIALTNSVNEALLNPSRVYTFFSSDYVKKVNKATEAAMFLGWVEQLVYDFTDET SEVSTTDKIADITIIIPYIGPALNIGNMLYKDDFVGALIFSGAVILLEFIPEIAIPVLGTFALVS YIANKVLTVQTIDNALSKRNEKWDEVYKYIVTNWLAKVNTQIDLIRKKMKEALENQAE ATKAIINYQYNQYTEEEKNNINFNIDDLSSKLNESINKAMININKFLNQCSVSYLMNSMIP YGVKRLEDFDASLKD ALLKYIYDNRGTLIGQVDRLKDKVNNTLSTDIPFQLSKYVDNQR LLSTFTEYIKNIINTSILNLRYESNHLIDLSRYASKINIGSKVNFDPIDKNQIQLFNLESSKIE VILKNAIVYNSMYENFSTSFWIRIPKYFNSISLNNEYTIINCMENNSGWKVSLNYGEIIWT LQDTQEIKQRVVFKYSQMINISDYINRWIFVTITNNRLNNSKIYINGRLIDQKPISNLGNIH ASNNIMFKLDGCRDTHRYIWIKYFNLFDKELNEKEIKDLYDNQSNSGILKDFWGDYLQY DKPYYMLNLYDPNKYIDVNNVGIRGYMYLKGPRGNVMTTNIYLNSSLYMGTKFIIKKY ASGNKDNIVRNNDRVYINVVVKNKEYRLATNASQAGVEKILSALEIPDVGNLSQVVVM KSKNDQGITNKCKMNLQDNNGNDIGFIGFHQFNNIAKLVASNWYNRQIERSSRTLGCSW EFIPVDDGWGERPL*SEQ ID NO: 62, PRT, Clostridium botulinum, heavy chain botulinum UPI0001A954C8MTKSLDKGYNKALNDLCIKVNNWDLFFSPSEDNFTNDLNKGEEITSDTNIEAAEENISLD LIQQ YYLTFNFDNEPENISIENL S SDIIGQLELMPNIERFPNGKKYELDK YTMFHYLRAQEF EHGKSRIALTNSVNEALLNPSRVYTFFSSDYVKKVNKATEAAMFLGWVEQLVYDFTDET SEVSTTDKIADITIIIPYIGPALNIGNMLYKDDFVGALIFSGAVILLEFIPEIAIPVLGTFALVS YIANKVLTVQTIDNALSKRNEKWDEVYKYIVTNWLAKVNTQIDLIRKKMKETLENQAE ATKAIINYQYNQYTEEEKNNINFNIDDLS SKLNESINK AM IN INKFLNQC S VS YLMNSMIP YGVKRLEDFDASLKD ALLKYI YDNRGTLIGQVDRLKDKVNNTLSTDIPFQLSKYVDNQR LLSTFTEYIKNIINTSILNLRYESNHLIDLSRYASKINIGSKVNFDPIDKNQIQLFNLESSKIE VILKNAIVYNSMYENFSTSFWIRIPKYFNSISLNNEYTIINCMENNSGWKVSLNYGEIIWT LQDTQEIKQRVVFKYSQMINISDYINRWIFVTITNNRLNNSKIYINGRLIDQKPISNLGNIH ASNNIMFKLDGCRDTHRYIWIKYFNLFDKELNEKEIKDLYDNQSNSGILKDFWGDYLQY DKPYYMLNLYDPNKYVDVNNVGIRGYMYLKGPRGSVMTTNIYLNSSLYRGTKFIIKKY ASGNKDNIVRNNDRVYINVVVKNKEYRLATNASQAGVEKILSALEIPDVGNLSQVVVM KSKNDQGITNKCKMNLQDNNGNDIGFIGFHQFNNIAKLVASNWYNRQIERS SRTLGC SW EFIPVDDGWGERPL*SEQ ID NO: 63, PRT, Clostridium botulinum, heavy chain botulinum UPI00027EE164MTKSLDKGYNKALNDLCIKVNNWDLFFSPSEDNFTNDLNKGEEITSDTNIEAAEENISLD LIQQ YYLTFNFDNEPENISIENL S SDIIGQLELMPNIERFPNGKKYELDKYTMFHYLRAQEF EHGKSRIALTNSVNEALLNPSRVYTFFSSDYVKKVNKATEAAMFLGWVEQLVYDFTDET SEVSTTDKIADITIIIPYIGPALNIGNMLYKDDFVGALIFSGAVILLEFIPEIAIPVLGTFALVS YIANKVLTVQTIDNALSKRNEKWDEVYKYIVTNWLAKVNTQIDLIRKKMKEALENQAE ATKAIINYQYNQYTEEEKNNINFNIDDLS SKLNE S INK AM IN INK F LNQC S VS YLMNSMIP YGVKRLEDFDASLKD ALLKYIYDNRGTLIGQVDRLKDKVNNTLSTDIPFQLSKYVDNQR LLSTFTEYIKNIINTSILNLRYESNHLIDLSRYASKINIGSKVNFDPIDKNQIQLFNLESSKIE VILKNAIVYNSMYENFSTSFWIRIPKYFNSISLNNEYTIINCMENNSGWKVSLNYGEIIWT LQDTQEIKQRVVFKYSQMINISDYINRWIFVTITNNRLNNSKIYINGRLIDQKPISNLGNIH ASNNIMFKLDGCRDTHRYIWIKYFNLFDKELNEKEIKDLYDNQSNSGILKDFWGDYLQY DKPYYMLNLYDPNKYVDVNNVGIRGYMYLKGPRGSVMTTNIYLNSSLYRGTKFIIKKY ASGNKDNIVRNNDRVYINVVVKNKEYRLATNASQAGVEKILSALEIPDVGNLSQVVVM KSKDDQGIRNKCKMNLQDNNGNDIGFIGFHLYDNIAKLVASNWYNRQIERASRTFGCSW EFIPVDDGWGES SL*SEQ ID NO: 64, PRT, Clostridium botulinum, heavy chain botulinum UPI000016EA88MTKSLDEGYNKALNDLCIKVNNWDLFFSPSEDNFTNDLDKVEEITADTNIEAAEENISLD LIQQ YYLTFDFDNEPENISIENL S SDIIGQLEPMPNIERFPNGKKYELDK YTMFHYLRAQEF EHGDSRIILTNSAEEALLKPNVAYTFFSSKYVKKINKAVEAFMFLNWAEELVYDFTDETN EVTTMDKIADITIIVPYIGPALNIGNMLSKGEFVEAIIFTGVVAMLEFIPEYALPVFGTFAIV SYIANKVLTVQTINNALSKRNEKWDEVYKYTVTNWLAKVNTQIDLIREKMKKALENQA EATKAIINYQYNQYTEEEKNNINFNIDDLSSKLNESINSAMININKFLDQCSVSYLMNSMI PYAVKRLKDFDASVRDVLLKYIYDNRGTLVLQVDRLKDEVNNTLSADIPFQLSKYVDNKKLLSTFTEYIKNIVNTSILSIVYKKDDLIDLSRYGAKINIGDRVYYDSIDKNQIKLINLESSTI EVILKNAIVYNSMYENF STSFWIKIPKYF SKINLNNEYTIINCIENNSGWKVSLNYGEIIWT LQDNKQNIQRVVFKYSQMVNISDYINRWIFVTITNNRLTKSKIYINGRLIDQKPISNLGNIH ASNKIMFKLDGCRDPRRYIMIKYFNLFDKELNEKEIKDLYDSQSNSGILKDFWGNYLQY DKPYYMLNLFDPNKYVDVNNIGIRGYMYLKGPRGSVVTTNIYLNSTLYEGTKFIIKKYAS GNEDNIVRNNDRVYINVVVKNKEYRLATNASQAGVEKILSALEIPDVGNLSQVVVMKS KDDQGIRNKCKMNLQDNNGNDIGFIGFHLYDNIAKLVASNWYNRQVGKASRTFGCSWE FIPVDDGWGESSL*SEQ ID NO: 65, PRT, Clostridium botulinum, heavy chain botulinum UPI000067C53EMTKSLDEGYNKALNDLCIKVNNWDLFFSPSEDNFTNDLDKVEEITADTNIEAAEENISLD LIQQ YYLTFDFDNEPENISIENL S SDIIGQLEPMPNIERFPNGKKYELDKYTMFHYLRAQEF EHGDSRIILTNSAEEALLKPNVAYTFFSSKYVKKINKAVEAFMFLNWAEELVYDFTDETN EVTTMDKIADITIIVPYIGPALNIGNMLSKGEFVEAIIFTGVVAMLEFIPEYALPVFGTFAIV SYIANKVLTVQTINNALSKRNEKWDEVYKYTVTNWLAKVNTQIDLIREKMKKALENQA EATKAIINYQYNQYTEEEKNNINFNIDDLSSKLNESINSAMININKFLDQCSVSYLMNSMI PYAVKRLKDFDASVRDVLLKYIYDNRGTLVLQVDRLKDEVNNTLSADIPFQLSKYVDNK KLLSTFTEYIKNIVNTSILSIVYKKDDLIDLSRYGAKINIGDRVYYDSIDKNQIKLINLESSTI EVILKNAIVYNSMYENF STSFWIKIPKYF SKINLNNEYTIINCIENNSGWKVSLNYGEIIWTLQDNKQNIQRVVFKYSQMVNISDYINRWIFVTITNNRLTKSKIYINGRLIDQKPISNLGNIH ASNKIMFKLDGCRDPRRYIMIKYFNLFDKELNEKEIKDLYDSQSNSG1LKDFWGNYLQY DKPYYMLNLFDPNKYVDVNNIGIRGYMYLKGPRGSVVTTNIYLNSTLYEGTKFIIKKYASGNEDNIVRNNDRVYINVVVKNKEYRLATNASQAGVEKILSALEIPDVGNLSQVVVMKS KDDQGIRNKCKMNLQDNNGNDIGLIGFHQFNNIAKLVASNWYNRQVGKASRTFGCSWE FIPVDDGWGESSL*SEQ ID NO: 66, PRT, Clostridium botulinum, heavy chain botulinum UPI0000EF84BDMTKSLDEGYNKALNDLCIKVNNWDLFFSPSEDNFTNDLDKVEEITADTNIEAAEENISLD LIQQYYLTFDFDNEPENISIENL S SDIIGQLEPMPNIERFPNGKKYELDK YTMFHYLRAQEF EHGDSRIILTNSAEEALLKPNVAYTFFSSKYVKKINKAVEAFMFLNWAEELVYDFTDETN EVTTMDKIADITIIVPYIGPALNIGNMLSKGEFVEAIIFTGVVAMLEFIPEYALPVFGTFAIV SYIANKVLTVQTINNALSKRNEKWDEVYKYTVTNWLAKVNTQIDLIREKMKKALENQA E ATKAIINYQ YNQ YTEEEKNNINFNIDDL S SKLNESINS AMININKFLDQC S VS YLMNSMI PYAVKRLKDFDASVRDVLLKYIYDNRGTLVLQVDRLKDEVNNTLSADIPFQLSKYVDNK KLLSTFTEYIKNIVNTSILSIVYKKDDLIDLSRYGAKINIGDRVYYDSIDKNQIKLINLESSTI EVILKNAIVYNSMYENF STSFWIKIPKYF SKINLNNEYTIINCIENNSGWKVSLNYGEIIWTLQDNKQNIQRVVFKYSQMVNISDYINRWIFVTITNNRLTKSKIYINGRLIDQKPISNLGNIH ASNKIMFKLDGCRDPRRYIMIKYFNLFDKELNEKEIKDLYDSQSNSGILKDFWGNYLQY DKPYYMLNLFDPNKYVDVNNIGIRGYMYLKGPRGRVVTTNIYLNSTLYEGTKFIIKKYASGNEDNIVRNNDRVYINVVVKNKEYRLATNASQAGVEKILSALEIPDVGNLSQVVVMKSKDDQGIRNKCKMNLQDNNGNDIGFIGFHLYDNIAKLVASNWYNRQVGKASRTFGCSWE FIPVDDGWGESSL*SEQ ID NO: 67, PRT, Clostridium botulinum, heavy chain botulinum UPI0001C0B376MTKSLDEGYNKALNDLCIKVNNWDLFFSPSEDNFTNDLDKVEEITADTNIEAAEENISLD LIQQYYLTFDFDNEPENISIENL S SDIIGQLEPMPNIERFPNGKKYELDK YTMFHYLRAQEF EHGDSRIILTNSAEEALLKPNVAYTFFSSKYVKKINKAVEAFMFLNWAEELVYDFTDETN EVTTMDKIADITIIVPYIGPALNIGNMISKGEFVEAIIFTGVVAMLEFIPEYALPVFGTFAIVS YIANKVLTVQTINNALSKRNEKWDEVYKYTVTNWLAKVNTQIDLIREKMKKALENQAE ATKAIINYQYNQYTEEEKNNWNIDDLS SKLNESINS AMININKFLDQC S VS YLMNSMIP YAVKRLKDFDASVRDVLLKYIYDNRGTLVLQVDRLKDEVNNTLSADIPFQLSKYVDNK KLLSTFTEYIKNIVNTSILSIVYKKDDLIDLSRYGAKINIGDRVYYDSIDKNQIKLINLESSTI EVILKNAIVYNSMYENF STSFWIKIPKYF SKINLNNEYTIINCIENNSGWKVSLNYGEIIWT LQDNKQNIQRVVFKYSQMVNISDYINRWIFVTITNNRLTKSKIYINGRLIDQKPISNLGNIH ASNKIMFKLDGCRDPRRYIMIKYFNLFDKELNEKEIKDLYDSQSNSGILKDFWGNYLQYDKPYYMLNLFDPNKYVDVNNIGIRGYMYLKGPRGSVVTTNIYLNSTLYEGTKFIIKKYAS GNEDNIVRNNDRVYINVVVKNKEYRLATNASQAGVEKILSALEIPDVGNLSQVVVMKS KDDQGIRNKCKMNLQDNNGNDIGFIGFHLYDNIAKLVASNWYNRQVGKASRTFGCSWE FIPVDDGWGESSL*SEQ ID NO: 68, PRT, Clostridium botulinum, heavy chain botulinum UPI0001C32E84MTKSLDEGYNKALNDLCIKVNNWDLFFSPSEDNFTNDLDKVEEITADTNIEAAEENISLD LIQQYYLTFDFDNEPENISIENL S SDIIGQLEPMPNIERFPNGKKYELDK YTMFHYLRAQEF EHGDSRIILTNSAEEALLKPNVAYTFFSSKYVKKINKAVEAFMFLNWAEELVYDFTDETN EVTTMDKIADITIIVPYIGPALNIGNMLSKGEFVEAIIFTGVVAMLEFIPEYALPVFGTFAIV SYIANKVLTVQTINNALSKRNEKWDEVYKYTVTNWLAKVNTQIDLIREKMKKALENQA EATKAIINYQYNQYTEEEKNNINFNIDDLSSKLNESINSAMININKFLDQCSVSYLMNSMI PYAVKRLKDFDASVRDVLLKYIYDNRGTLILQVDRLKAEVNNTLSTDIPFQLSKYVENK KLLSTFTEYIKNITNTSILSIVVDKDDELIDLSRYGAEIYRGDKVFYNSIDKNQIKLINLESS TIEVILKNAIVYNSMYENFSTSFWIKIPKYFSKINLNNEYTIINCIENNSGWKVSLNYGEII WTLQDNKQNIQRVVFKYSQMVNISDYINRWIFVTITNNRLTKSKIYINGRLIDQKLISNLG NIHASNKIMFKLDGCRDPGRYIVIKYFNLFDKELNEKEIKDLYDSQSNSGILKDFWGDYLQYDKPYYMLNLYDPNKYVDVNNIGIRGYMYLKGPRGSVVTTNIYLNSTLYMGTKFIIKK YASGNEDN1VRNNDRVY1NVVVKNKEYRLATNASQAGVEKILSALE1PDVGNLSQLVVM KSKDDQGIRNKCKMNLQDNNGNDIGLIGFHQFNNIAKLVASNWYNRQVGKASRTFGCS WEFIPVDDGWGESSQ*SEQ ID NO: 69, PRT, Clostridium botulinum, heavy chain botulinum UPI0001F3B30DMTKSLDEGYNKALNDLCIKVNNWDLFFSPSEDNFTNDLDKVEEITADTNIEAAEENISLDLIQQYYLTFDFDNEPENISIENLSSDIIGQLEPMPNIERFPNGKKYELDKYTMFHYLRAQEFEHGD SRIILTNS AEEALLKPNVAYTFF S SKYVKKINK AVE AFMFLNWAEELVYDFTDETN EVTTMDKIADITIIVPYIGPALNIGNMLSKGEFVEAIIFTGVVAMLEFIPEYALPVFGTFAIV SYIANKVLTVQTINNALSKRNEKWDEVYKYTVTNWLAKVNTQIDLIREKMKKALENQA EATK AIINYQ YNQ YTEEEKNNINFNIDDL S SKLNESINS AMININKFLDQC S VS YLMNSMI PYAVKRLKDFDASVRDVLLKYIYDNRGTLVLQVDRLKDEVNNTLSADIPFQLSKYVDNK KLLSTFTEYIKNIVNTSILSIVYKKDDLIDLSRYGAKINIGDRVYYDSIDKNQIKLINLESSTI EVILKNAIVYNSMYENF STSFWIKIPKYF SKINLNNEYTIINCIENNSGWKVSLNYGEIIWT LQDNKQNIQRVVFKYSQMVNISDYINRWIFVTITNNRLTKSKIYINGRLIDQKPISNLGNIH ASNKIMFKLDGCRDPRRYIMIKYFNLFDKELNEKEIKDLYDSQSNSGILKDFWGNYLQY DKPYYMLNLFDPNKYVDVNNIGIRGYMYLKGPRGSVVTTNIYLNSTLYEGTKFIIKKYAS GNEDNIVRNNDRVYINVVVKNKEYRLATNASQAGVEKILSALEIPDVGNLSQVVVMKS KDDQGIRNKCKMNLQDNNGNDIGFIGFHLYDNIAKLVASNWYNRQVGKASRTFGCSWE FIPVDDGWGESSL*SEQ ID NO: 70, PRT, Clostridium botulinum, heavy chain botulinum UPI000290BDD5MTKSLDEGYNKALNDLCIKVNNWDLFFSPSEDNFTNDLDKVEEITADTNIEAAEENISLD LIQQ YYLTFDFDNEPENISIENL S SDIIGQLEPMPNIERFPNGKKYELDK YTMFHYLRAQEF EHGD SRIILTNS AEEALLKPNVAYTFFSSKYVKKINKAVE AFMFLNWAEELVYDFTDETN EVTTMDKIADITIIVPYIGPALNIGNMLSKGEFVEAIIFTGVVAMLEFIPEYALPVFGTFAIV SYIANKVLTVQTINNALSKRNEKWDEVYKYTVTNWLAKVNTQIDLIREKMKKALENQA EATKA1INYQYNQYTEEEKNNINFNIDDLSSKLNESINSAMININKFLDQCSVSYLMNSM1 PYAVKRLKDFDASVRDVLLKYIYDNRGTLVLQVDRLKDEVNNTLSADIPFQLSKYVDNK KLLSTFTEYIKNIVNTSILSIVYKKDDLIDLSRYGAKINIGDRVYYDSIDKNQIKLINLESSTI EVILKNAIVYNSMYENF STSFWIKIPKYF SKINLNNEYTIINCIENNSGWKVSLNYGEIIWT LQDNKQNIQRVVFKYSQMVNISDYINRWIFVTITNNRLTKSKIYINGRLIDQKPISNLGNIH ASNKIMFKLDGCRDPRRYIMIKYFNLFDKELNEKEIKDLYDSQSNSGILKDFWGNYLQY DKPYYMLNLFDPNKYVDVNNIGIRGYMYLKGPRGSVVTTNIYLNSTLYEGTKFIIKKYAS GNEDNIVRNNDRVYINVVVKNKEYRLATNASQAGVEKILSALEIPDVGNLSQVVVMKS KDDQGIRNKCKMNLQDNNGNDIGLIGFHQFNNIAKLVASNWYNRQVGKASRTFGCSWE FIPVDDGWGESSQ*SEQ ID NO: 71, PRT, Clostridium botulinum, heavy chain botulinum UPI000290BEB 1MTKSLDEGYNKALNDLCIKVNNWDLFFSPSEDNFTNDLDKVEEITADTNIEAAEENISLD LIQQYYLTFDFDNEPENISIENLSSDIIGQLEPMPNIERFPNGKKYELDKYTMFHYLRAQEF EHGD SRIILTNS AEEALLKPNVAYTFFSSKYVKKINKAVE AFMFLNWAEELVYDFTDETN EVTTMDKIADITIIVPYIGPALNIGNMLSKGEFVEAIIFTGVVAMLEFIPEYALPVFGTFAIV SYIANKVLTVQTINNALSKRNEKWDEVYKYTVTNWLAKVNTQIDLIREKMKKALENQA EATKAIINYQYNQYTEEEKNNINFNIDDLSSKLNESINSAMININKFLDQCSVSYLMNSMI PYAVKRLKDFDASVRDVLLKYIYDNRGTLVLQVDRLKDEVNNTLSADIPFQLSKYVDNK KLLSTFTEYIKNIVNTSILSIVYKKDDLIDLSRYGAKINIGDRVYYDSIDKNQIKLINLESSTI EVILKNAIVYNSMYENF STSFWIKIPKYF SKINLNNEYTIINCIENNSGWKVSLNYGEIIWTLQDNKQNIQRVVFKYSQMVNISDYINRWIFVTITNNRLTKSKIYINGRLIDQKPISNLGNIH ASNKIMFKLDGCRDPRRYIMIKYFNLFDKELNEKEIKDLYDSQSNSGILKDFWGNYLQY DKPYYMLNLFDPNKYVDVNNIGIRGYMYLKGPRGSVVTTNIYLNSTLYEGTKFIIKKYAS GNEDNIVRNNDRVYINVVVKNKEYRLATNASQAGVEKILSALEIPDVGNLSQVVVMKS KDDQGIRNKCKMNLQDNNGNDIGFIGFHLYDNIAKLVASNWYNRQVGKASRTFGCSWE FIPVDDGWGESSL*SEQ ID NO: 72, PRT, Clostridium botulinum, heavy chain botulinum UPI0004A59983MTKSLDEGYNKALNDLCIKVNNWDLFFSPSEDNFTNDLDKVEEITADTNIEAAEENISLD LIQQ YYLTFDFDNEPENISIENL S SDIIGQLEPMPNIERFPNGKKYELDK YTMFHYLRAQEF EHGDSR1ILTN S AEEALLKPN VAYTFF S SK Y VKKINKAVEAFMFLN WAEELV YDFTDETN EVTTMDKIADITIIVPYIGPALNIGNMLSKGEFVEAIIFTGVVAMLEFIPEYALPVFGTFAIV SYIANKVLTVQTINNALSKRNEKWNEVYKYTVTNWLAKVNTQIDLIREKMKKALENQA EATKAIINYQYNQYTEEEKNNINFNIDDLSSKLNESINSAMININKFLDQCSVSYLMNSMI PYAVKRLKDFDASVRDVLLKYIYDNRGTLVLQVDRLKDEVNNTLSADIPFQLSKYVDNK KLLSTFTEYIKNIVNTSILSIVYKKDDLIDLSRYGAKINIGDRVYYDSIDKNQIKLINLESSTI EVILKNAIVYNSMYENF STSFWIKIPKYF SKINLNNEYTIINCIENNSGWKVSLNYGEIIWT LQDNKQNIQRVVFKYSQMVNISDYINRWIFVTITNNRLTKSKIYINGRLIDQKPISNLGNIH ASNKIMFKLDGCRDPRRYIMIKYFNLFDKELNEKEIKDLYDSQSNSGILKDFWGNYLQY DKPYYMLNLFDPNKYVDVNNIGIRGYMYLKGPRGSVVTTNIYLNSTLYKGTKFIIKKYA SGNEDNIVRNNDRVYINVVVKNKEYRLATNASQAGVEKILSALEIPDVGNLSQVVVMKS KDDQGIRNKCKMNLQDNNGNDIGFIGFHLYDNIAKLVASNWYNRQVGKASRTFGCSWE FIPVDDGWGESSL*SEQ ID NO: 73, PRT, Clostridium botulinum, heavy chain botulinum UPI00005B712CMTKSLDEGYNKALNYLCIKVNNWDLFF SPSEDNFTNDLDKVEEITADTNIEAAEENIS SD LIQQYYLTFDFDNEPENISIENLSSDIIGQLEPMPNIERFPNGKKYELDKYTMFHYLRAQEF EHGD SRIILTNS AEEALLKPNVAYTFF S SK YVKKINKAVEAVIFLS WAEELVYDFTDETNE VTTMDKIADITIIVPYIGPALNIGNMVSKGEFVEAILFTGVVALLEFIPEYSLPVFGTFAIVS YIANI<VLTVQTINNALSI<RNEI<WDEVYKYTVTNWLAI<VNTQIDLIREI<MI<I<ALENQAE ATRAIINYQYNQYTEEEKNNINFNIDDLSSKLNRSINRAMININKFLDQCSVSYLMNSMIP YAVKRLKDFDASVRDVLLKYIYDNRGTLILQVDRLKDEVNNTLSADIPFQLSKYVNDKK LLSTFTEYIKNIVNTSILSIVYKKDDLIDLSRYGAKINIGDRVYYDSIDKNQIKLINLESSTIE VILKNAIVYNSMYENFSTSFWIKIPKYFSKINLNNEYTIINCIENNSGWKVSLNYGEIIWTL QDNKQNIQRVVFKYSQMVNISDYINRWMFVTITNNRLTKSKIYINGRLIDQKPISNLGNIH ASNKIMFKLDGCRDPRRYIMIKYFNLFDKELNEKEIKDLYDSQSNPGILKDFWGNYLQY DKPYYMLNLFDPNKYVDVNNIGIRGYMYLKGPRGSVMTTNIYLNSTLYMGTKFIIKKYA SGNEDNIVRNNDRVYINVVVKNKEYRLATNASQAGVEKILSALEIPDVGNLSQVVVMKS KDDQGIRNKCKMNLQDNNGNDIGFVGFHLYDNIAKLVASNWYNRQVGKASRTFGCSW EFIPVDDGWGES SL*SEQ ID NO: 74, PRT, Clostridium botulinum, heavy chain botulinum UPI00016DBC11MTKSLDEGYNKALNDLCIKVNNWDLFF SPSEDNFTNDLDKVEEITADTNIEAAEENIS SD LIQQ YYLTFDFDNEPENISIENL S SDIIGQLEPMPNIERFPNGKKYELDK YTMFHYLRAQEF EHGD SRIILTNS AEEALLKPNVAYTFF S SK YVKKINKAVEAVIFLS WAEELVYDFTDETNE VTTMDKIADITIIVPYIGPALNIGNMVSKGEFVEAILFTGVVALLEFIPEYSLPVFGTFAIVS YIANI<VLTVQTINNALSI<RNEI<WDEVYI<YTVTNWLAI<VNTQIDLIREI<MKKALENQAE ATRAIINYQYNQYTEEEKNNINFNIDDLSSKLNRSINRAMININKFLDQCSVSYLMNSMIP YAVKRLKDFDASVRDVLLKYIYDNRGTLILQVDRLKDEVNNTLSADIPFQLSKYVNDKK LLSTFTEYIKNIVNTSILSIVYKKDDLIDLSRYGAKINIGDRVYYDSIDKNQIKLINLESSTIE VILKNAIVYNSMYENFSTSFWIKIPKYFSKINLNNEYTIINCIENNSGWKVSLNYGEIIWTL QDNKQNIQRVVFKYSQMVNISDYINRWMFVTITNNRLTKSKIYINGRLIDQKPISNLGNIH ASNKIMFKLDGCRDPRRYIMIKYFNLFDKELNEKEIKDLYDSQSNPGILKDFWGNYLQY DKPYYMLNLFDPNKYVDVNNIGIRGYMYLKGPRGSVMTTNIYLNSTLYMGTKFIIKKYA SGNEDNIVRNNDRVYINVVVKNKEYRLATNASQAGVEKILSALEIPDVGNLSQVVVMKS KDDQGIRNKCKMNLQDNNGNDIGFVGFHLYDNIAKLVASNWYNRQVGKASRTFGCSW EFIPVDDGWGESSL*SEQ ID NO: 75, PRT, Clostridium botulinum, heavy chain botulinum UPI000290C3D0MTKSLDEGYNKALNDLCIKVNNWDLFFSPSEDNFTNDLDKVEEITADTNIEAAEENISSD LIQQ YYLTFDFDNEPENISIENL S SDIIGQLEPMPNIERFPNGKKYELDK YTMFHYLRAQEF EHGD SRIILTNS AEEALLKPNVAYTFF S SK YVKKINKAVEAVIFLS WAEELVYDFTDETNE VTTMDKIADITIIVPYIGPALNIGNMVSKGEFVEAILFTGVVALLEFIPEYSLPVFGTFAIVS YIANKVLTVQTINNALSKRNEKWDEVYKYTVTNWLAKVNTQIDLIREKMKKALENQAE ATRAIINYQYNQYTEEEKNNINFNIDDLSSKLNRSINRAMININKFLDQCSVSYLMNSMIP YAVKRLKDFDASVRDVLLKYIYDNRGTLILQVDRLKDEVNNTLSADIPFQLSKYVNDKK LLSTFTEYIKNIVNTSILSIVYKKDDLIDLSRYGAKINIGDRVYYDSIDKNQIKLINLESSTIE VILKNAIVYNSMYENFSTSFWIKIPKYFSKINLNNEYTIINCIENNSGWKVSLNYGEIIWTL QDNKQNIQRVVFKYSQMVNISDYINRWMFVTITNNRLTKSKIYINGRLIDQKPISNLGNIH ASNKIMFKLDGCRDPRRYIMIKYFNLFDKELNEKEIKDLYDSQSNPGILKDFWGNYLQY DKPYYMLNLFDPNKYVDVNNIGIRGYMYLKGPRGSVMTTNIYLNSTLYMGTKFIIKKYA SGNEDNIVRNNDRVYINVVVKNKEYRLATNASQAGVEKILSALEIPDVGNLSQVVVMKS KDDQGIRNKCKMNLQDNNGNDIGFIGFHLYDNIAKLVASNWYNRQVGKASRTFGCSWE FIPVDDGWGESSL*SEQ ID NO: 76, PRT, Clostridium botulinum, heavy chain botulinum UPI00005B712DMTKSLDEGYNKALNELCIKVNNWDLFFSPSEDNFTNDLDKVEEITSDTNIEAAEENISLD LIQQYYLNFNFDNEPENTSIENLSSDIIGQLEPMPNIERFPNGKKYELNKYTMFHYLRAQE FKHSNSRIILTNSAKEALLKPNIVYTFFSSKYIKAINKAVEAVTFVNWIENLVYDFTDETNE VSTMDKIADITIVIPYIGPALNIGNMIYKGEFVEAIIFSGAVILLEIVPEIALPVLGTFALVSYVSNKVLTVQTIDNALSKRNEKWDEVYKYIVTNWLAIVNTQTNLIREKMKKALENQAEAT KAIINYQYNQYTEEEKNNINFNIDDLSSKLNESINSAMININKFLDQCSVSYLMNSMIPYA VKRLKDFDASVRDVLLKYIYDNRGTLIGQVNRLKDKVNNTLSADIPFQLSKYVDNKKLL STFTEYIKNITNASILSIVYKDDDLIDLSRYGAEIYNGDKVYYNSIDKNQIRLINLESSTIEVI LKKAIVYNSMYENFSTSFWIRIPKYFNSISLNNEYTIINCMENNSGWKVSLNYGEIIWTFQ DTQEIKQRVVFKYSQMINISDYINRWIFVTITNNRITKSKIYINGRLIDQKPISNLGNIHASN KIMFKLDGCRDPHRYIVIKYFNLFDKELSEKEIKDLYDNQSNSGILKDFWGDYLQYDKSY YMLNLYDPNKYVDVNNVGIRGYMYLKGPRDNVMTTNIYLNSSLYMGTKFIIKKYASGN KDNIVRNNDRVYINVVVKNKEYRLATNASQAGVEKILSALEIPDVGNLSQVVVMKSKN DQGITNKCKMNLQDNNGNDIGFIGFHQFNNIAKLVASNWYNRQIERS SRTLGC S WEFIP V DDGWRERPL*SEQ ID NO: 77, PRT, Clostridium botulinum, heavy chain botulinum UPI00019DB885MTKSLDEGYNKALNELCIKVNNWDLFFSPSEDNFTNDLDKVEEITSDTNIEAAEENISLD LIQQYYLNFNFDNEPENTSIENLSSDIIGQLEPMPNIERFPNGKKYELNKYTMFHYLRAQE FKHSNSRIILTNSAKEALLKPNIVYTFFSSKYIKAINKAVEAVTFVNWIENLVYDFTDETNE VSTMDKIADITIVIPYIGPALNIGNMIYKGEFVEAIIFSGAVILLEIVPEIALPVLGTFALVSY VSNKVLTVQTIDNALSKRNEKWDEVYKYIVTNWLAIVNTQINLIREKMKKALENQAEAT KAIINYQYNQ YTEEEKNNINFNIDDLS SKLNESINS AM IMNKFLDQC S VS YLMNSM IP YA VKRLKDFDASVRDVLLKYIYDNRGTLIGQVNRLKDKVNNTLSADIPFQLSKYVDNKKLL STFTEYIKN1TNASILSIVYKDDDLIDLSRYGAEIYNGDKVYYNSIDKNQIRLINLESSTIEVI LKKAIVYNSMYENFSTSFWIRIPKYFNSISLNNEYTIINCMENNSGWKVSLNYGEIIWTLQ DTQEIKQRVVFKYSQMINISDYINRWIFVTITNNRITKSKIYINGRLIDQKPISNLGNIHASN KIMFKLDGCRDPHRYIVIKYFNLFDKELSEKEIKDLYDNQSNSGILKDFWGDYLQYDKSY YMLNLYDPNKYVDVNNVGIRGYMYLKGPRDNVMTTNIYLNSSLYMGTKFIIKKYASGN KDNIVRNNDRVYINVVVKNKEYRLATNASQAGVEKILSALEIPDVGNLSQVVVMKSKN DQGITNKCKMNLQDNNGNDIGFIGFHQFNNIAKLVASNWYNRQIERS SRTLGC S WEFIP V DDGWRERPL*SEQ ID NO: 78, PRT, Clostridium botulinum, heavy chain botulinum UPI000198BDAEMTKSLDEGYNKALNDLCIKVNNWDLFFSPSEDNFTNDLNKGEEITSDTNIEAAEENISLD LIQQ YYLTFNFDNEPENISIENL S SDIIGQLELMPNIERFPNGKKYELDKYTMFHYLRAQEF EHGKSRIVLTNS VNE ALLNP S S VYTFF S SD YVRKVNKATE AAMFLGW VEQLVYDFTDET SEVSTTDKIAD1TIIIPYIGPALNIGNMLYKDDFVGALIFSGAVILLEFIPEIAIPVLGTFALVS YIANKVLTVQTIDNALSKRNEKWGEVYKYIVTNWLAKVNTQIDLIRKKMKEALENQAE ATKAIINYQ YNQ YTEEEKNNINFNIGDLS SKLND S I NK AM I N I NK F LNQC S VS YLMN S M IP YGVKRLEDFDASLKDALLKYIYDNRGTLIGQVDRLKDKVNNTLSTDIPFQLSKYVDNQR LLSTFTEYIKNIINTSILNLRYESNHLIDLSRYASEINIGSKVNFDPIDKNQIQLFNLESSKIEII LKNAIVYNSMYENFSTSFWIKIPKYFSKINLNNEYTIINCIENNSGWKVSLNYGEIIWTLQ DNKQNIQRVVFKYSQMVAISDYINRWIFITITNNRLNNSKIYINGRLIDQKPISNLGNIHAS NNIMFKLDGCRDPHRYIWIKYFNLFDKELNEKEIKDLYDNQSNSGILKDFWGNYLQYDKPYYMLNLYDPNKYVDVNNVGIRGYMYLKGPRGSIVTTNIYLNSSLYMGTKFIIKKYASG NKDNIVRNNDRVYINVVVKNKEYRLATNASQAGVEKILSVLEIPDVGNLSQVVVMKSK NDQGIRNKCKMNLQDNNGNDIGFIGFHQFNNIDKLVASNWYNRQIERSSRTFGCSWEFIP VDDGWGESPL*SEQ ID NO: 79, PRT, Clostridium botulinum, heavy chain botulinum UPI0001AE7D6AMTKSLDEGYNKALNDLCIKVNNWDLFFSPSEDNFTNDLNKGEEITSDTNIEAAEENISLD LIQQ YYLTFNFDNEPENISIENL S SDIIGQLELMPNIERFPNGKKYELDK YTMFHYLRAQEF EHGKSRIVLTNS VNEALLNP S S VYTFF S SD YVRKVNKATE AAMFLGWVEQLVYDFTDET SEVSTTDKIADITIIIPYIGPALNIGNMLYKDDFVGALIFSGAVILLEFIPEIAIPVLGTFALVS YIANKVLTVQTIDNALSKRNEKWGEVYKYIVTNWLAKVNTQIDLIRKKMKEALENQAE ATKAIINYQ YNQ YTEEEKNNINFNIGDLS SKLND S I NK AM I N I NK F LNQC S VS YLMN S M IP YGVKRLEDFDASLKD ALLKYI YDNRGTLIGQVDRLKDKVNNTLSTDIPFQLSKYVDNQR LLSTFTEYIKNIINTSILNLRYESNHLIDLSRYASEINIGSKVNFDPIDKNQIQLFNLESSKIEII LKNAIVYNSMYENFSTSFWIKIPKYFSKINLNNEYTIINCIENNSGWKVSLNYGEIIWTLQ DNKQNIQRVVFKYSQMVAISDYINRWIFITITNNRLNNSKIYINGRLIDQKPISNLGNIHAS NNIMFKLDGCRDPQRYIWIKYFNLFDKELNEKEIKDLYDNQSNSGILKDFWGNYLQYDK PYYMLNLYDPNKYVDVNNVGIRGYMYLKGPRGSIVTTNIYLNSSLYMGTKFIIKKYASG NKDNIVRNNDRVYINVVVKNKEYRLATNASQAGVEKILSVLEIPDVGNLSQVVVMKSK NDQGIRNKCKMNLQDNNGNDIGFIGFHQFNNIDKLVASNWYNRQIERSSRTFGCSWEFIP VDDGWGESPL*SEQ ID NO: 80, PRT, Clostridium botulinum, heavy chain botulinum UPI0001B7D251MTK SLDKGYNKALNDLCIK VNNWDLFF SP SEDNFTNDLNKGEEIT SDTNIEAAEENISLD LIQQ YYLTFNFDNEPENISIENL S SDIIGQLELMPNIERFPNGKKYELDK YTMFHYL SAQEF EHGKSRIDLTNSVNEALLNPSHVYTFFSSDYVKKVNKATEAAMFLGWVEQLVYDFTDET SEVSTTDKIADITIIIPYIGPALNIGNMLYKDDFVGALIFSGAVILLEFIPEIAIPVLGTFAIVSY IANKVLTVQTINNALSKRNEI<WDEVYI<YTVTNWLAKVNTQIDLIREI<MKKALENQAEA TKAIINYQ YNQ YTEEEKNNINFNIDDL S SKLNESINS AM ININK FLDQC S VS YLMNSMIP Y AVKRLKDFDASVRDVLLKYIYDNRGTLIGQVDRLKDKVNNTLSTDIPFQLSKYVDNQRL L S TF TE Y I K N 11 N T SIL SLRYENNHLIDL SRYASKINIGSRVNFDPIDKNQIQLFNLE S S K I E VI LKNAIVYNSMYENFSTSFWIKIPKYFSEISLNNEYTIINCIENNSGWKVSLNYGEIIWTLQD NKQNIQRVVFKYSQMVAISDYINRWIFITITNNRLTKSKIYINGRLIDQKPISNLGNIHASN KIMFKLDGCRDPRRYIMIKYFNLFDKELNEKEIKDLYDSQSNSGILKDFWGNYLQYDKP YYMLNLFDPNKYVDVNNVGIRGYMYLKGSRSTLLTTNIYLNSGLYMGTKFIIKKYASGN KDNIVRNNDRVYINVVVNNKEYRLATNASQAGVEKILSALEIPDIGNLSQVVVMKSKND QGIRNKCKMNLQDNNGNDIGFIGFHKFNDIYKLVASNWYNRQIEISSRTFGCSWEFIPVD DGWGEKPL*SEQ ID NO: 81, PRT, Clostridium botulinum, heavy chain botulinum UPI000290B995MTKSLDEGYNKALNDLCIKVNNWDLFFSPSEDNFTNDLNKGEEITSDTNIEAAEENISSD LIQQ YYLTFNFDNEPENISIENL S SDIIGQLELMPNIERFPNGKKYELDK YTMFHYLRAQEF EYGNSRIVLINS VNEALLNPS S VYTFF S SDYVKKANEATEAAMFLGWVEQLVYDFTDET SEVSTMDKIADITIIVPYIGPALNIGNMVYKKKFEEALIFSGAVILLEFVPEIVLPILGTFALV SYTSNKVLTVRTIDNALSKRNEKWEEVYKYIVTNWLAKVNTQINLIRKKMKEALENQA EATKAIINYQ YNQ YTEEEKNNINFNIGDL S SKLND S INK AM I N INK F LDQC S VS YLMNSMI PQGVKQLKDFDTSLRDSLLKYIYDNRGTLIGQVDRLKDKVNNTLSTDIPFQLSKYADNQ RLLSTFTEYIKNIINTSILNLRYESNHLIDLSRYASKINIGSRVNFDPIDKNQIQLFNLESSKIE VILKNAIVYNSMYENFSTSFWIKIPKYFSKINLNNEYTIINCIENNSGWKVSLNYGEIIWTL QDNEQNIQRVVFKYSQMVNISDYINRWIFVTITNNRLTKSKIYINGRLIDQKPISNLGNIHA SNKIMFKLDGCRDPHRYILIKYFNLFDKELNEKEIKDLYDNQSNSGILKDFWGDYLQYD KPYYMLNLYDPNKYIDVNNIGIRGYMYLKGPRGSVTTTNIYLNSMLYMGTKFIIKKHAS GNKDNIVRNNDRVYINVLVKNKEYRLATNASQAGGEKILSAVEIPDVGNLSQVVVMKSK NDQGIRNKCKMNLQDNNGNDIGFIGFHQFNNIAKLVASNW YNRQIGKT S VTLGC S WELI PVDYGWGESSL*SEQ ID NO: 82, PRT, Clostridium botulinum, heavy chain botulinum UPI0003C9D2A1MTKSLDEGYNKALNDLCIKVNNWDLFFSPSEDNFTNDLDKVEEITSDTNIEAAEENISLD LIQQ YYLTFDFDNEPENISIENL S SDIIGQLEPMPNIERFPNGKKYELDKYTMFHYLRAQEF EHSKSRIALTNSVNEALLNPSRVYTFFSSDYVKKVNKATEAAMFLGWVEQLVYDFTDET SEVSTTDKIAD1TIIIPYIGPALNIGNMLYKDDFVGALIFSGAVILLEFIPEIAIPVLGTFALVS YIANI<VLTVQTIDNALSKRNEI<WDEVYI<YIVTNWLAKVNTQIDLVRKKMKEALENQAE ATKAIINYQYNQYTEEEKNNINFNIDDLSSKLNESINSAMTNINKFLDQCSVSYLMNSMIP YAVKRLKDFDASVREVLLKYIYDNRGTLILQVDRLKDKVNNTLSADIPFQLSKYVDNKK LLSTFTEYIKNITNTSILSIVVDKDGRLIDLSRYGAEIYNGDKVSYNSIDKNQIKLINLESSA IEVILKNAIVYNSMYENFSTSFWIKIPKYFSKINLNNEYTIINCIENNSGWKVSLNYGEIIW TLQDNQQNIQRVVFKYSQMVNISDYINRWIFVTITNNRLDKSKIYINGRLIDQKPISNLGNI HASNNIMFKLDGCRDPRRYIVIKYFNLFDKELNEKEIKDLYDNQSNSGILKDFWGDYLQ YDKPYYMLNLYDPNKYVDVNNIGIRGYMYLKGPRGSVVTTNIYLNSTLYMGTKFIIKKY ASGNKDNIVRNNDRVYINVVVKNKEYRLATNALQAGVEKILSALEIPDVGNLSQVVVM KSKNDQGIRNKCKMNLQDNNGNDIGLIGFHQFNNIAKLVASNWYNRQVGKASRTFGCS WEFIP VDDGWGES SQ *SEQ ID NO: 83, PRT, Clostridium botulinum, heavy chain botulinum UPI000559A469MTKSLDEGYNKALNDLCIKVNNWDLFFSPSEDNFTNDLDKVEEITSDTNIEAAEENISLD LIQQ YYLTFDFDNEPENISIENL S SDIIGQLEPMPNIERFPNGKKYELDK YTMFHYLRAQEF EHSKSRIALTNSVNEALLNPSRVYTFFSSDYVKKVNKATEAAMFLGWVEQLVYDFTDET SEVSTTDKIADITIIIPYIGPALNIGNMLYKDDFVGALIFSGAVILLEFIPEIAIPVLGTFALVS YIANKVLTVQTIDNALSKRNEKWDEVYKYIVTNWLAKVNTQIDLVRKKMKEALENQAE ATKAIINYQYNQYTEEEKNNINFNIDDLSSKLNESINSAMTNINKFLDQCSVSYLMNSMIP YAVKRLKDFDASVREVLLKYIYDNRGTLILQVDRLKDKVNNTLSADIPFQLSKYVDNKKLLSTFTEYIKNITNTSILSIVVDKDGRLIDLSRYGAEIYNGDKVSYNSIDKNQIKLINLESSA IEVILKNAIVYNSMYENFSTSFWIKIPKYFSKINLNNEYTIINCIENNSGWKVSLNYGEIIW TLQDNQQNIQRVVFKYSQMVNISDYINRWIFVTITNNRLDKSKIYINGRLIDQKPISNLGNI HASNNIMFKLDGCRDPRRYIVIKYFNLFDKELNEKEIKDLYDNQSNSGILKDFWGDYLQ YDKPYYMLNLYDPNKYVDVNNIGIRGYMYLKGPRGSVVTTNIYLNSTLYMGTKFIIKKY ASGNKDNIVRNNDRVYINVVVKNKEYRLATNALQAGVEKILSALEIPDVGNLSQVVVM KSKNDQGIRNKCKMNLQDNNGNDIGLIGFHQFNNIAKLVASNWYNRQVGKASRTFGCS WEFIPVDDGWGESSQ*SEQ ID NO: 84, PRT, Clostridium botulinum, heavy chain botulinum UPI0000001386MTKSLDKGYNKALNDLCIKVNNWDLFFSPSEDNFTNDLNKGEE1TSDTNIEAAEENISLD LIQQ YYLTFNFDNEPENISIENL S SDIIGQLELMPNIERFPNGKKYELDK YTMFHYLRAQEF EHGKSRIALTNSVNEALLNPSRVYTFFSSDYVKKVNKATEAAMFLGWVEQLVYDFTDET SEVSTTDKIADITIIIPYIGPALNIGNMLYKDDFVGALIFSGAVILLEFIPEIAIPVLGTFALVS YIANKVLTVQTIDNALSKRNEKWDEVYKYIVTNWLAKVNTQIDLIRKKMKEALENQAE ATKAIINYQ YNQ YTEEEKNNINFNIDDLS SKLNE S INK AM IN INK F LNQC S VS YLMNSMIP YGVKRLEDFDASLKD ALLKYI YDNRGTLIGQVDRLKDKVNNTLSTDIPFQLSKYVDNQR LLSTFTEYIKNIINTSILNLRYESNHLIDLSRYASKINIGSKVNFDPIDKNQIQLFNLESSKIE VILKNAIVYNSMYENFSTSFWIRIPKYFNSISLNNEYTIINCMENNSGWKVSLNYGEIIWT LQDTQEIKQRVVFKYSQMINISDYINRWIFVTITNNRLNNSKIYINGRLIDQKPISNLGNIH ASNNIMFKLDGCRDTHRY1WIKYFNLFDKELNEKEIKDLYDNQSNSGILKDFWGDYLQY DKPYYMLNLYDPNKYVDVNNVGIRGYMYLKGPRGSVMTTNIYLNSSLYRGTKFIIKKY ASGNKDNIVRNNDRVYINVVVKNKEYRLATNASQAGVEKILSALEIPDVGNLSQVVVM KSKNDQGITNKCKMNLQDNNGNDIGFIGFHQFNNIAKLVASNWYNRQIERSSRTLGCSW EFIPVDDGWGERPL*SEQ ID NO: 85, RNA, Clostridium botulinum, light chain botulinum, UPI0000ED909E1 gaggaaauaa gagagaaaag aagaguaaga agaaauauaa gagccaccau gccauucgug61 aauaaacaau ucaacuauaa ggauccuguc aacggcgugg auauagcuua uaucaagauu121 ccuaauguag ggcagaugca acccgugaag gcauuuaaaa uccauaacaa gauuuggguc181 auaccagaac gagauaccuu caccaacccu gaggagggcg accugaaucc acccccugag241 gccaaacaag ugccaguguc auacuaugau aguacguacc ugaguacgga caacgaaaag301 gauaauuauc uuaaaggggu uacuaaacuc uuugaaagaa ucuauucuac agacuuggga361 cggauguuac ugaccuccau cgugcgcggc aucccguuuu gggguggauc cacaaucgac421 acagagcuca aaguuauaga uacuaacugu aucaacguga uucagccuga ugggagcuau481 aggucagaag agcucaaccu gguaaucauu ggacccucug cagacauaau ccaguucgag541 ugcaaaucuu uuggccacga agugcuaaau uugacucgga auggauacgg uagcacucag 601 uacauccguu uuagcccaga uuucaccuuc ggcuucgagg agagccugga agucgacacu 661 aaccccuugc ugggagcagg caaauucgcc accgacccgg cgguuacauu ggcccacgag 721 uuaauucaug cuggccacag gcuguauggu aucgcuauca aucccaacag gguuuuuaag 781 gugaauacaa acgcuuauua cgagauguca gggcuggaag uaagcuuuga ggagcugcgc 841 accuuugggg gacaugacgc uaaauuuauu gauucgcuac aggagaauga auuucgacug 901 uacuauuaca acaaguucaa agacauugca uccacccuga acaaggccaa gaguaucguc 961 gggaccacag ccucacucca guacaugaag aauguuuuca aagagaagua ccugcugucu 1021 gaggauacgu ccggaaaauu cagcgucgac aaacucaaau ucgauaagcu uuacaagaug 1081 cucaccgaaa ucuacacaga ggacaauuuu gugaaauucu ucaaggucuu gaauagaaag 1141 accuaccuga acuuugacaa ggcgguguuc aagauuaaca ucgugcccaa ggucaacuau 1201 acaauauaug acggcuucaa ccuucggaau acuaaccuug ccgccaauuu caacgggcag 1261 aauacugaaa uuaauaauau gaauuucaca aaauuaaaga acuuuacugg ccuguuugaa 1321 uuuuacaagc uccuuugcgu gagagguauu auuaccucca agugagcggc cgcuuaauua 1381 agcugccuuc ugcggggcuu gccuucuggc caugcccuuc uucucucccu ugcaccugua 1441 ccucuugguc uuugaauaaa gccugaguag gaagaaaaaa aaaaaaaaaa aaaaaaaaaa 1501 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 1561 aaaaaaaaaa aaaaSEQ ID NO: 86, RNA, Clostridium botulinum, light chain botulinum UPI0000EF85BD1 gaggaaauaa gagagaaaag aagaguaaga agaaauauaa gagccaccau gcccuucgug61 aauaaacagu uuaauuacaa ggaccccgua aacggcgugg acauugccua caucaaaauc121 ccuaacgugg gccaaaugca gccuguuaaa gcauuuaaga uccacaauaa gauauggguu 181 auaccagaga gagauacuuu cacuaauccu gaggagggag aucugaaccc gccuccagaa 241 gcuaagcaag uccccgucuc uuauuacgau agcacauauu uguccaccga caaugagaaa 301 gauaacuacc ucaagggugu gacuaaacug uucgaaagaa ucuacagcac agaucugggg 361 aggauguugc ugacgaguau cguuagggga aucccauuuu gggguggcuc cacuaucgau 421 acugagcuua aggugaucga cacgaacugc auuaacguga uacagccuga ugggaguuac481 cguucugagg aauuaaaccu ggucauuauu ggccccuccg ccgacaucau acaauucgaa541 uguaaaagcu ucggccauga agugcucaau uugacucgga auggcuaugg gaguacacag601 uacauucggu uuucaccaga cuucacauuc ggguuugagg aaucacucga gguggacacc661 aacccccugc ugggcgcugg caaguuugcu acagacccag ccgugacucu ggcucacgaa721 uugauucaug cgggacauag acuauauggg aucgcaauua acccgaaccg ggucuuuaag781 guuaacacaa augccuauua ugagauguca ggucucgaag ugucauucga ggaacuucgc841 accuuuggag ggcacgacgc aaaauucauc gauucucuuc aggagaacga guuccgauug901 uacuacuaua acaaauuuaa ggacauugca uccacccuua auaaggcgaa gagcauugua961 ggaaccacag ccagccugca guacaugaaa aaugucuuca aggaaaagua ucuacugucg1021 gaagacacgu cugggaaguu cagcguagau aagcugaaau uugacaagcu cuauaaaaug1081 cugaccgaga uuuauacaga ggacaauuuu gucaaguuuu ucaaggugcu caacaggaaa1141 accuauuuaa acuucgauaa ggccguguuc aaaauaaaca ucguccccaa agugaauuac1201 accaucuacg augguuucaa ucuucgaaau accaauuuag cugccaacuu caacggacag1261 aauaccgaga uuaauaauau gaacuucacc aagcugaaaa acuuuacagg acucuuugag1321 uuuuacaaac ugcugugcgu ucgcggcauc aucacuucca agugagcggc cgcuuaauua1381 agcugccuuc ugcggggcuu gccuucuggc caugcccuuc uucucucccu ugcaccugua1441 ccucuugguc uuugaauaaa gccugaguag gaagaaaaaa aaaaaaaaaa aaaaaaaaaa1501 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa1561 aaaaaaaaaa aaaaSEQ ID NO: 87, RNA, Clostridium botulinum, heavy chain botulinum UPI0001A954C81 gaggaaauaa gagagaaaag aagaguaaga agaaauauaa gagccaccau gccuuuuguu61 aauaaacagu ucaauuacaa ggacccugug aauggggugg acaucgcaua caucaagauc121 ccaaaugcag gucagaugca gcccguaaag gccuucaaga uccauaauaa gauuuggguc181 auucccgagc gagacacguu cacuaaucca gaggagggag accugaaccc gccuccagaa241 gccaagcagg uucccgucuc uuauuaugau ucuacauacc uuaguacaga caaugagaaa301 gauaacuacu ugaagggggu gaccaagcug uuugagagga uauauucuac ugaucucgga361 agaaugcugc uuacuucuau cguucggggc auccccuuuu ggggugguuc aacaauugac421 accgagcuua agguuaucga uacuaauugc aucaacguca uucaaccaga uggcagcuau 481 cggagcgaag agcugaaucu cguaaucauc ggcccuagcg cagacauuau ccaauucgaa 541 ugcaagagcu ucgggcacga aguguugaac cucacucgga acggguaugg gucgacccaa 601 uacauucgcu uuuccccaga uuucacauuu ggcuucgaag aaucccugga gguggauacc 661 aauccucugc ugggugccgg aaaauuugcc acggaccccg cagugacacu ggcucaugag 721 uuaauacaug cuggccacag acucuacggc auugcgauca accccaaucg cguauuuaaa 781 gucaacacaa acgccuauua cgaaaugagu ggacuggaag uuaguuucga ggagcucaga 841 acauucggag gccacgacgc caaguucauu gacucacugc aggagaacga guuucgacuu 901 uacuacuaua acaaauuuaa agauauagcu uccacccuca auaaggcuaa gagcauugug 961 ggaacuaccg ccucauugca guacaugaag aauguguuca aagaaaagua uuuguuauca 1021 gaggacacga gcgggaaauu cuccgucgac aaauugaaau uugauaaguu auauaagaug 1081 cugacugaaa ucuauacaga ggauaacuuu gugaaguucu ucaaagugcu aaaucguaaa 1141 accuaccuca acuuugacaa ggcugucuuc aaaauuaaca ucgugccgaa agugaacuac 1201 accauauaug auggguucaa ccugaggaau accaaccugg ccgcgaauuu uaauggccag 1261 aacacagaga ucaacaauau gaacuuuacc aagcuuaaaa acuuuaccgg ccuguucgaa 1321 uucuacaagc ugcuaugugu caggggaaua auuacuucca aaugagcggc cgcuuaauua 1381 agcugccuuc ugcggggcuu gccuucuggc caugcccuuc uucucucccu ugcaccugua 1441 ccucuugguc uuugaauaaa gccugaguag gaagaaaaaa aaaaaaaaaa aaaaaaaaaa 1501 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 1561 aaaaaaaaaa aaaaSEQ ID NO: 88, RNA, Clostridium botulinum, heavy chain botulinum UPI00027EE1641 gaggaaauaa gagagaaaag aagaguaaga agaaauauaa gagccaccau gccuuuuguu61 aauaagcagu uuaacuacaa ggacccggua aauggugugg auauugcaua uauuaaaauu 121 ccaaacgcug gccagaugca gcccguuaag gcauucaaga uccauaauaa gauauggguc 181 auucccgagc gugauaccuu cacaaacccu gaggaggggg aucugaaccc acccccugag 241 gccaaacagg ugcccgucuc cuauuaugau ucuacuuacc ucagcacaga caacgagaag301 gacaauuacc ugaaaggggu cacaaagcug uuugaacgca uuuauaguac ggacuugggg 361 aggaugcucu uaacuagcau aguuaggggc auccccuuuu ggggaggauc uaccaucgau 421 acugagcuga aggucaucga uacgaauugc aucaacguga uucaaccaga cggcucauac 481 cggucugaag agcugaaucu cgugaucauc gguccgagcg cagauauuau acaguuugaa 541 ugcaaaucau ucgggcacga ggugcugaac cuaacucgga acggguaugg aagcacccag 601 uauaucaggu ucaguccaga cuucaccuuc gguuucgagg agagccucga ggucgauacu 661 aacccauuau ugggagccgg caaguucgcg accgaucccg ccgucacacu ugcccaugaa 721 cugauacacg cugggcacag acuuuacggg aucgccauca auccuaauag aguauuuaag 781 guuaauacca acgcguacua ugagaugucu ggacuggagg ucuccuucga agaacuccga 841 acauuuggag gacaugaugc uaaguuuauc gacuccuugc aagagaacga auucagacuu 901 uacuacuaca auaaauucaa agacauugca ucgacccuua auaaggccaa guccauagug 961 ggcaccaccg cuucccugca guacaugaaa aacguuuuua aagaaaagua ccuccuguca 1021 gaggacacaa gcggcaaauu uaguguagac aaacugaaau uugacaaguu guacaaaaug 1081 cugacugaaa uuuauaccga agacaacuuu gugaaguucu ucaaagugcu gaaccggaag 1141 acguaucuaa auuucgacaa ggccguguuc aaaaucaaua ucgugccuaa agugaacuau 1201 acuauuuaug auggcuucaa uuuacgaaac acaaacuugg cugccaauuu uaacggccaa 1261 aacacugaga ucaauaacau gaauuucacc aagcucaaga auuuuacagg ucuuuucgaa 1321 uuuuacaaac ugcugugugu gcgcggcauu aucacaucaa agugagcggc cgcuuaauua 1381 agcugccuuc ugcggggcuu gccuucuggc caugcccuuc uucucucccu ugcaccugua 1441 ccucuugguc uuugaauaaa gccugaguag gaagaaaaaa aaaaaaaaaa aaaaaaaaaa 1501 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 1561 aaaaaaaaaa aaaaSEQ ID NO: 89, RNA, Clostridium botulinum, light chain botulinum, UPI0000110A421 gaggaaauaa gagagaaaag aagaguaaga agaaauauaa gagccaccau gccauucguu61 aacaaacagu uuaacuauaa ggacccuguc aauggcgugg acauugcaua uaucaaaauu121 ccaaacguag ggcagaugca gcccgucaaa gcguucaaga uacauaacaa gaucuggguu181 auuccagaac gcgauacguu uaccaacccu gaggagggcg accugaaucc cccaccggag241 gcaaaacaag ugccuguauc cuacuaugau uccacuuauc ugucaacaga caaugagaaa301 gacaauuacc uuaagggcgu gacuaaguug uucgagagaa ucuauucgac agaccugggg361 cgcaugcugu ugacgucuau uguccgcggg auuccuuuuu gggggggaag caccaucgac421 acugagcuca aggugaucga caccaauugu aucaacguga uccagccgga uggcucauac481 agaucagagg aacucaacuu agugauaauc ggcccaagcg cagacaucau ucaguucgaa541 ugcaaaucau ucggccacga gguccugaau uugacccgua auggauacgg aucuacccag601 uacauucggu ucagucccga cuucaccuuc ggauuugaag agucccuuga agucgauaca661 aauccccugc uuggugccgg caaguuugcc accgaucccg ccguuacccu cgcgcacgag721 cugauucaug caggucacag acuguacggg aucgccauca auccuaaucg agucuuuaaa781 gugaacacaa augcuuauua cgaaaugucu ggucucgagg uguccuuuga agaguugagg841 acuuucgggg gacaugaugc caaauucauc gacagccuuc aagaaaacga guucaggcug901 uauuacuaua acaaguuuaa ggauaucgcu agcacacuca acaaggcuaa guccaucgua961 gguaccacug ccagucugca guacaugaag aauguuuuua aagagaagua ccucuuaagc1021 gaagauacua guggaaaauu uagcguugac aagcugaaau uugauaagcu uuauaaaaug1081 uugacggaga uuuacacuga agacaauuuu gugaaguucu uuaaagugcu aaaccggaag1141 acauaucuga acuucgauaa agcuguguuc aaaauaaaua uugugcccaa ggucaacuac1201 acaauauacg auggauuuaa ucugaggaac acaaauuuag ccgcuaauuu caacgggcaa1261 aacaccgaga ucaacaauau gaacuucaca aaacuaaaga acuucacugg ccucuucgaa1321 uuuuauaagc ugcugugcgu gcggggcaua auuaccucua agugagcggc cgcuuaauua1381 agcugccuuc ugcggggcuu gccuucuggc caugcccuuc uucucucccu ugcaccugua1441 ccucuugguc uuugaauaaa gccugaguag gaagaaaaaa aaaaaaaaaa aaaaaaaaaa1501 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa1561 aaaaaaaaaa aaaaSEQ ID NO: 90, RNA, Clostridium botulinum, light chain botulinum, UPI000003409D1 gaggaaauaa gagagaaaag aagaguaaga agaaauauaa gagccaccau gcaguuugug61 aacaagcagu uuaauuacaa ggacccagug aaugggguag auauagccua uauuaagauu121 cccaaugugg gacaaaugca gccagugaag gcguucaaaa uccauaacaa gaucugggua181 auuccugaga gggauaccuu cacaaacccc gaagaaggcg auuugaaccc accuccggaa241 gcuaaacagg ucccggugag uuacuacgau uccacguacc ugagcacaga caaugagaaa301 gauaacuauc ucaagggcgu cacuaagcuc uuugagagaa uuuauucuac cgaccugggc361 cgaaugcucc ugacaaguau aguccgaggc aucccuuucu gggguggauc gacaaucgau421 acugaacuga aagucauuga uacuaacugu auuaacguga uucagccuga cgggucauau481 cggagcgaag agcucaacuu agugaucaua gggcccucug cagacaucau ucaguucgaa541 ugcaaaucau ucggccacga aguucugaac cuuacccgca acggguacgg uaguacucag601 uauauucguu ucuccccaga cuuuacuuuc ggauucgagg aaagcuuaga gguugacacc661 aaucccuugc uuggugccgg gaaauucgcu accgauccag ccgugacacu ggcacacgag721 uugauccacg cuggacauag guuguacggg aucgcuauaa acccuaacag agucuuuaaa781 guuaauacaa acgcguacua ugagaugucc ggacucgagg ugagcuucga ggaguugcgg841 accuucggcg gucaugacgc caaguuuauc gauucacucc aagaaaauga guuccggcug901 uauuauuaua auaaguuuaa ggacauugcc ucuacccuga acaaggcaaa guccaucguc961 ggcacgacug ccagccugca auauaugaag aaugucuuca aggagaaaua cuuacuguca1021 gaggacacau cuggcaaguu uuccguggau aaacugaaau uugauaaacu cuacaaaaug1081 cugacggaaa uauacacaga agacaauuuc gugaaauucu uuaaggugcu gaacaggaag1141 acuuaccuaa auuuugacaa ggcuguguuc aaaaucaaua ucguucccaa aguaaacuac1201 acuaucuacg acggcuuuaa ucuuagaaau acaaaccuag ccgcaaauuu caauggacag1261 aacaccgaga ucaauaacau gaauuuuacc aagcugaaga acuuuaccgg gcuuuuugag1321 uucuauaagc ugcuuugcgu ucgcggaauu aucaccagca aaugagcggc cgcuuaauua1381 agcugccuuc ugcggggcuu gccuucuggc caugcccuuc uucucucccu ugcaccugua1441 ccucuugguc uuugaauaaa gccugaguag gaagaaaaaa aaaaaaaaaa aaaaaaaaaa1501 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa1561 aaaaaaaaaa aaaaSEQ ID NO: 91, RNA, Clostridium botulinum, light chain botulinum, UPI00016529B71 gaggaaauaa gagagaaaag aagaguaaga agaaauauaa gagccaccau gccuuuugug61 aacaaacagu uuaauuacaa agaccccguu aacggugugg auaucgcgua uauuaagauu 121 ccaaacgugg gucagaugca gccuguuaag gccuucaaga uccacaauaa aaucugggua 181 auuccggagc gggacaccuu uacaaauccc gaggaaggug aucuuaaccc ccccccagag 241 gccaagcagg uuccuguguc cuacuacgac agcacuuacc ugaguaccga caacgagaag 301 gauaauuacc uuaagggcgu gacaaaguug uucgagcgaa uuuauucgac cgaccucggc 361 aggauguuau uaacaucuau aguccgagga auuccuuuuu ggggggguag cacuauugac 421 acggagcuga aagugaucga uaccaacugu aucaauguca uccaaccaga cggaucuuac 481 agauccgagg agcugaaucu ggugauuauu ggacccagug cagacauuau ccaguuugaa 541 ugcaagagcu ucggacacga agucuugaac cucacuagaa auggcuacgg cagcacccag 601 uauauucggu uuagucccga uuucaccuuc ggguuugaag agucacucga aguggacacu 661 aauccucucc uuggggccgg gaaauucgca accgauccag cuguuaccuu ggcccaugaa 721 cugauccaug caggacacag acuuuauggc aucgcgauaa auccgaaccg cgucuuuaag 781 gugaacacga acgccuacua ugagauguca gggcuggagg ucuccuucga agaacucagg 841 acuuucggcg gacaugacgc aaaauucaua gauucucugc aagaaaacga guucaggcuu 901 uauuauuaua auaaguuuaa ggauaucgcu ucuacgcuaa acaaagccaa guccaucguu 961 gggacaacag ccucacugca guauaugaag aaugucuuca aggagaagua cuuguuaagc 1021 gaggauacaa gcggcaaguu uuccguggau aagcugaaau uugacaaacu guacaagaug 1081 uugacagaaa ucuauaccga ggacaauuuc gucaaguuuu ucaaaguacu gaaucgcaaa 1141 acuuaccuga acuucgauaa agcuguguuc aaaauuaaca uagugccaaa agugaauuac 1201 acuaucuaug acggcuucaa ucuccggaac accaaucugg cugcuaacuu caacgggcaa 1261 aacaccgaga ucaauaacau gaacuucacu aaacugaaga auuuuacagg ccuguuugaa 1321 uuuuacaaac uccuaugcgu acguggaauc auaacaucaa agugagcggc cgcuuaauua 1381 agcugccuuc ugcggggcuu gccuucuggc caugcccuuc uucucucccu ugcaccugua 1441 ccucuugguc uuugaauaaa gccugaguag gaagaaaaaa aaaaaaaaaa aaaaaaaaaa 1501 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa1561 aaaaaaaaaa aaaaSEQ ID NO: 92, RNA, Clostridium botulinum, light chain botulinum, UPI0000EF84BD1 gaggaaauaa gagagaaaag aagaguaaga agaaauauaa gagccaccau gccauuuguc61 aauaagcaau uuaauuacaa ggacccugug aacggaguag acauugcaua uaucaaaauc121 ccuaacgccg gucaaaugca gcccguuaaa gcauuuaaaa uccauaauaa gauauggguu181 auccccgaac gcgacacuuu uaccaacccu gaagagggag aucuuaaucc accaccggag241 gcaaagcagg ucccuguguc auacuacgau ucaacguacu ugagcacuga uaacgagaaa301 gauaauuauc ugaagggagu gacgaaacuu uuugaaagga ucuacuccac ugaucugggc361 agaaugcuuc ucaccaguau aguuaggggc auuccuuucu ggggcggguc aacuauagac421 acagagcuga agguaaucga caccaacugc auaaauguga uucagccuga cggaucauau481 cgaucugagg agcuuaaccu cgugaucauc gggcccucug cugauauuau ucaguuugaa541 ugcaaaucgu ucggccacga ugucuuaaau cuuacccgua acggguaugg guccacccag601 uacauucggu ucuccccaga uuucacuuuu ggcuuugagg agagucugga aguggacacu661 aacccgcucc ugggggccgg uaaauucgcc accgacccag ccgugacguu agcgcaugaa721 cugauucacg cugagcaucg gcucuauggu aucgcuauaa accccaauag aguuuucaag781 gugaacacaa acgcauacua cgagaugagc ggcuuggagg ugaguuucga agagcuacgc841 accuucggag gacacgaugc uaaauucauc gauagucucc aagagaauga guucagacug901 uauuacuaca auaaauuuaa ggacgucgcu uccacacuga acaaggccaa aagcauuauu961 ggcacaacag cgagccucca guauaugaaa aacgucuuca aggaaaagua ucuguuaagc1021 gaagauaccu ccgggaaauu uagcguggac aagcugaagu uugacaagcu auauaagaug1081 cugacagaga ucuacacaga agacaacuuc gugaauuucu ucaaaguaau caacaggaag1141 acuuaucuga acuuugacaa agccguguuc cgaauuaaua ucguucccga ugagaauuac1201 accauuaagg acgguuuuaa ccugaagggc gccaaucugu cuacaaacuu uaacgggcag1261 aacaccgaaa ucaauucucg caauuucacu cggcucaaga auuucaccgg cuuguucgaa1321 uuuuacaagu uguugugugu caggggaauc auucccuuua aaugagcggc cgcuuaauua1381 agcugccuuc ugcggggcuu gccuucuggc caugcccuuc uucucucccu ugcaccugua1441 ccucuugguc uuugaauaaa gccugaguag gaagaaaaaa aaaaaaaaaa aaaaaaaaaa1501 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa1561 aaaaaaaaaa aaaaSEQ ID NO: 93, RNA, Clostridium botulinum, light chain botulinum, UPI0001C0B3761 gaggaaauaa gagagaaaag aagaguaaga agaaauauaa gagccaccau gccuuucgug61 aauaaacagu uuaauuacaa ggacccuguc aauggcgugg acaucgcuua uaucaaaauc121 ccuaaugcgg gccaaaugca gccugugaaa gccuucaaga uucauaacaa aauuuggguc181 auccccgagc gggacacauu uacuaacccc gaggaagggg accugaaucc accacccgag241 gcuaaacaag uccccguuuc cuauuacgau ucaacuuacu uaagcacuga caaugagaag301 gauaauuacu ugaagggugu aacuaaguug uucgagagga uauacucuac cgaccugggc361 cguaugcugc uaacuagcau cgugcggggu auuccauucu ggggcggguc caccauugac421 accgagcuga aaguaaucga uacgaauugu aucaauguga uacagccaga cggcaguuac481 aggagugagg aacugaacuu ggucaucauu ggaccuuccg ccgacauuau ccaguuugaa541 ugcaaaucuu ucggacauga uguacucaau uugaccagaa augguuaugg auccacccag601 uacauuagau ucagcccgga uuuuaccuuc ggauucgagg aaucccugga ggucgauaca661 aacccauugc ucggcgcagg caaauucgcu acagacccug ccgugacccu ggcccaugaa721 cugauucacg ccgaacaccg ccucuauggg auugcgauaa accccaaccg ggucuuuaag781 guuaacacaa acgcauacua ugaaauguca ggacuggaag ugucguucga ggaacugcgc841 accuuuggcg gucacgaugc aaaguuuaua gacucuuuac aggaaaauga guuuaggcuu901 uauuacuaca acaaguuuaa ggacguugcu agcacucuca auaaagccaa gaguaucauc961 ggaaccacag caagccucca auacaugaaa aacguuuuca aagagaagua ucuccugagc1021 gaagacacaa guggcaaauu cucuguggau aagcucaagu uugauaagcu uuauaaaaug1081 cuaacugaga ucuauaccga ggauaacuuc aucaacuucu uuaaggugau aaaccgaaag1141 acguaucuua auuucgauaa agccguuuuc agaauuaaca ucgugccgga ugagaacuac1201 acuaucaagg acggguuuaa ccugaaggga gcuaaucugu caacaaauuu uaacgggcag1261 aacacagaaa uuaacucacg aaauuucacg aggcugaaga acuucaccgg gcuuuuugag1321 uuuuacaagu uacuuugcgu gcgcgggaua auucccuuua aaugagcggc cgcuuaauua1381 agcugccuuc ugcggggcuu gccuucuggc caugcccuuc uucucucccu ugcaccugua1441 ccucuugguc uuugaauaaa gccugaguag gaagaaaaaa aaaaaaaaaa aaaaaaaaaa1501 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa1561 aaaaaaaaaa aaaaSEQ ID NO: 94, RNA, Clostridium botulinum, light chain botulinum, UPI0001C32E841 gaggaaauaa gagagaaaag aagaguaaga agaaauauaa gagccaccau gccauuuguu61 aacaagcagu uuaauuacaa agaccccgua aacggaguug acauugcaua caucaaaauc121 ccgaacgcug ggcagaugca gccugugaag gcauucaaaa uucauaacaa aaucugggua181 auccccgaga gagauacauu caccaaucca gaagagggcg acuugaaucc cccgccugag241 gcaaagcaag ugccugucag cuacuaugau ucuacguauc ugaguacuga caacgaaaaa301 gauaacuauc uaaagggagu uaccaaguug uucgaaagga ucuauagcac agaccucgga361 agaauguuac ugacuucaau agugcgugga auaccuuucu ggggcggaag cacaaucgac421 acugagcuga aggucaucga uaccaauugc aucaacguua uccagccaga cggauccuac481 cgcucagaag aacuuaaccu ggugauuauu gggccuucag ccgacaucau ucaauuugag541 ugcaagucuu ucggacauga uguguugaac cugacucgaa auggguacgg cuccacgcaa601 uacauuaggu uuagcccaga cuuuaccuuc gguuuugagg agucccuuga aguggauacc661 aacccacugu ugggugcggg caaguuugcu acagaucccg ccguuacacu cgcgcacgag721 cugauucacg cagagcauag gcuguacggc auugccauua aucccaaccg ggucuucaag781 gugaauacca augcuuauua cgagaugucc gggcuugaag ucucuuucga ggagcuucgg841 accuucggcg ggcacgaugc uaaguucaua gacucacucc aggagaauga guuucgcuug901 uauuauuaca auaaauucaa agauguggcu aguacccuga acaaggccaa gaguaucauu961 ggcaccacug ccucccucca guauaugaag aauguguuua aagaaaaaua ccuccuaagc1021 gaggauacau cugguaaauu caguguggac aaguuaaagu ucgacaaacu cuacaagaug1081 cuuacggaaa ucuauaccga agauaacuuu gugaacuucu uuaaggucau aaaccgcaag1141 acauaccuga acuucgacaa ggccgucuuc aggaucaaca ucgugcccga cgaaaauuau1201 acuauuaaag auggcuuuaa ccugaaaggg gccaaucuga gcaccaauuu uaacggucag1261 aauacagaga uuaauucgcg gaacuuuacu agacugaaaa auuuuacugg gcuguucgaa1321 uuuuacaagc ucuuaugugu acgaggcauc auaccuuuca aaugagcggc cgcuuaauua1381 agcugccuuc ugcggggcuu gccuucuggc caugcccuuc uucucucccu ugcaccugua1441 ccucuugguc uuugaauaaa gccugaguag gaagaaaaaa aaaaaaaaaa aaaaaaaaaa1501 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa1561 aaaaaaaaaa aaaaSEQ ID NO: 95, RNA, Clostridium botulinum, light chain botulinum, UPI0001F3B30D1 gaggaaauaa gagagaaaag aagaguaaga agaaauauaa gagccaccau gccauucgug61 aacaaacagu ucaacuauaa agaccccgug aauggcguug auaucgcaua uaucaagauc121 cccaaugccg gucaaaugca gccggugaag gccuucaaga uucauaacaa aauuugggua181 auuccugaac gagacaccuu cacuaauccg gaggagggug aucucaaucc ucccccagaa241 gcuaaacagg ugcccguaag cuacuacgac aguacuuacu ugucuaccga caacgagaag301 gauaauuauu ugaaaggagu gaccaagcuc uuugagcgga ucuauaguac ggaucucgga361 cgcauguuac ugacuucuau cguaaggggu aucccuuucu ggggcggcag cacaauagau421 acggaacuga aggugaucga cacaaauugc auaaauguga uacaaccaga cggauccuau481 agaagugagg aguugaaccu cgucaucauc ggccccucag cggauauuau ucaguuugag541 uguaagagcu ucgggcacga cgugcuuaau cugacacgua auggcuacgg gaguacucaa601 uauauucgcu uuagcccaga cuucaccuuu ggauuugagg aguccuugga gguugauaca661 aacccacugc uuggcgccgg ggaauucgca accgaucccg cugucacacu ggcccacgaa721 uugauacacg cagaacauag gcucuacggg auugcuauua acccuaaucg aguuuucaaa781 gucaacacua acgcguacua cgaaaugucu ggacuggaag ucucauucga agagcugaga841 acguucggug gacaugacgc caaauucauu gauagcuuac aggagaauga guuuaggcuc901 uacuauuaca auaaauucaa ggauguggcc ucgacccuua acaaagccaa auccaucauc961 gggaccacag cuucacuuca guacaugaag aaugucuuua aggaaaagua ccugcuguca1021 gaggauaccu ccggaaaauu uucuguugac aaacuaaagu ucgacaaacu guacaagaug1081 cugaccgaga uuuauacaga agacaauuuu guuaacuucu uuaaggugau caacagaaag1141 acuuaucuga auuucgacaa agcagucuuu cggauuaaca uagugccuga ugagaacuac1201 acuaucaaag acggcuuuaa ccuaaagggg gcuaaccucu ccaccaacuu uaacggccag1261 aacacugaaa ucaauagcag gaauuucaca cgccugaaga acuuuaccgg ccuuuuugag1321 uuuuauaagu uacugugcgu gcgggggauu aucccuuuca agugagcggc cgcuuaauua1381 agcugccuuc ugcggggcuu gccuucuggc caugcccuuc uucucucccu ugcaccugua1441 ccucuugguc uuugaauaaa gccugaguag gaagaaaaaa aaaaaaaaaa aaaaaaaaaa1501 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa1561 aaaaaaaaaa aaaaSEQ ID NO: 96, RNA, Clostridium botulinum, light chain botulinum, UPI0004A599831 gaggaaauaa gagagaaaag aagaguaaga agaaauauaa gagccaccau gccauucgug61 aauaagcaau uuaauuacaa agauccagug aacggcgugg auaucgccua cauuaaaauc121 cccaacgccg gccagaugca gccugugaag gcauucaaga uucauaacaa aauaugggua181 aucccggaga gagacaccuu cacuaauccc gaagagggag acuuaaaucc ucccccggaa241 gcaaagcaag uccccgucag cuauuaugau uccacauauc ugagcacuga uaaugagaaa301 gauaacuauc ucaaaggcgu cacgaagcug uuugagcgca uuuauuccac cgaucucggg361 agaaugcucc ugacuucuau ugugcgggga auaccuuucu ggggcgggag uacaaucgac421 accgaacuca agguuaucga caccaacugc aucaacguca uacaaccuga cggcucauac481 cgaagugagg aguugaaccu gguuaucauc gggccaucag cugacauuau ucaguuugag541 uguaagagcu uuggacacga ugugcugaac uugacucgca auggcuaugg uucuacgcag601 uacauucgau ucaguccaga uuuuaccuuc ggcuucgagg aaucccucga aguggauacu661 aauccccugu uaggcgccgg gaaauucgcu acagacccug cagucacccu agcucaugag721 uuaauucacg cugaacauag gcuguacggu aucgcuauua accccaaucg cguguuuaaa781 guuaacacca augccuauua cgaaaugucc gggcuggagg ugaguuucga ggaguugagg841 accuucggag gacacgacgc gaaguuuauu gauucgcucc aggaaaacga guuccgucuu901 uauuacuaca auaaguuuaa ggacguugcc ucaacccuga acaaagcaaa gagcauaauc961 gggacaacug ccagccuuca guacaugaag aacguguuua aagagaagua ccugcugagc1021 gaagauacau cuggcaaauu cucuguggac aagcuuaaau uugacaagcu guacaagaug1081 cugacugaaa ucuauacaga ggacaacuuu guaaauuucu ucaaaguaau uaacaggaaa1141 acuuaccuaa auuuugacaa agccguguuc cggaucaaua uagucccaga cgaaaacuac1201 accaucaagg auggauuuaa cuugaaggga gcgaaccucu caacgaacuu caaugggcag1261 aauacagaaa uuaauuccag gaauuuuacc agacuuaaaa acuuuacagg uuuguucgag1321 uucuauaagc ugcuuugcgu ucgggguauc aucccuuuua agugagcggc cgcuuaauua1381 agcugccuuc ugcggggcuu gccuucuggc caugcccuuc uucucucccu ugcaccugua1441 ccucuugguc uuugaauaaa gccugaguag gaagaaaaaa aaaaaaaaaa aaaaaaaaaa1501 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa1561 aaaaaaaaaa aaaaSEQ ID NO: 97, RNA, Clostridium botulinum, light chain botulinum, UPI000016EA881 gaggaaauaa gagagaaaag aagaguaaga agaaauauaa gagccaccau gcccuucgug61 aauaagcagu ucaauuauaa ggauccagug aacggcgugg auaucgccua caucaagauc121 ccuaacgcag gacagaugca gccagugaaa gccuucaaga uucacaauaa gauuuggguu181 aucccugaga gggacaccuu uaccaauccc gaggagggug aucucaaccc accaccagaa241 gcaaagcagg ugcccgugag uuauuacgac ucaaccuauc ucucuacaga caaugagaaa301 gacaacuauc ugaagggcgu cacuaagcuu uucgaacgga ucuauuccac cgaucuugga361 aggaugcugc ucaccuccau ugugaggggc aucccuuuuu gggggggcuc aacaauugau421 acagagcuca aaguaauuga uaccaauugc aucaacguua uccagccgga cggaagcuau481 agaagcgagg agcuaaaucu ggugauaauc gggcccuccg ccgacauuau ccaauuugaa541 ugcaagaguu ucggccauga uguauugaau cucacgcgaa auggauacgg guccacucaa601 uacauccgcu ucucaccuga cuucacuuuu ggguucgagg agucguugga aguggauaca661 aacccgcugc ugggugccgg caaauuugcu acggaucccg cugugacucu cgcccaugaa721 cuuauacaug ccgaacacag acuuuacgga aucgcuauua auccuaaccg ggucuuuaaa781 gugaauacaa augccuacua cgagaugagc ggcuuggagg ucagcuucga agagcugcgu841 acuuuugggg gucacgaugc gaaguucaua gauagccucc aggaaaacga guuuagacua901 uacuacuaca auaaauucaa ggacgucgca aguaccuuaa acaaggcaaa gucaauuauu961 gggacuaccg cuuccuuaca auauaugaaa aacguguuca aagaaaaaua ucuguugucu1021 gaagacacca guggcaaguu uagcguugau aaguuaaaau ucgacaaacu guacaaaaug1081 cugaccgaga uuuacacgga ggacaacuuu gucaacuuuu ucaaaguuau caaucgaaaa1141 accuaccuua acuuugacaa ggcuguauuc cgcauaaaca ucgucccuga cgaaaacuau1201 acaaucaagg acgguuuuaa ccugaaaggc gcgaaucugu cuacaaacuu uaacgggcag1261 aacacugaga uuaacucucg gaauuucaca cgccugaaga auuuuacugg auuguucgaa1321 uuuuauaagc ugcugugugu uaggggaauu auacccuuca agugagcggc cgcuuaauua1381 agcugccuuc ugcggggcuu gccuucuggc caugcccuuc uucucucccu ugcaccugua1441 ccucuugguc uuugaauaaa gccugaguag gaagaaaaaa aaaaaaaaaa aaaaaaaaaa1501 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa1561 aaaaaaaaaa aaaaSEQ ID NO: 98, RNA, Clostridium botulinum, light chain botulinum, UPI000067C53E1 gaggaaauaa gagagaaaag aagaguaaga agaaauauaa gagccaccau gccauucguu61 aauaagcagu uuaacuacaa ggauccugug aauggcguag acaucgccua cauuaagauc121 cccaacgccg gacagaugca acccguuaaa gccuuuaaga uucacaauaa aauuuggguc181 auacccgagc gcgacacuuu uacuaauccu gaggaaggag aucugaaccc uccacccgaa241 gcuaagcaag ucccagugag uuacuaugau agcacauauc ugucaaccga uaacgagaag301 gacaauuauu ugaagggcgu uaccaagcuc uucgaaagga ucuacuccac cgacuugggc361 agaaugcugc ugacuagcau cgugcgugga auuccguuuu ggggggguuc uaccaucgau421 acagagcuga aagucaucga uacgaacugc auaaauguga uccaaccaga cgggucguau481 cgguccgagg agcuaaacuu agugauaauc gggcccucug ccgacauuau acaguucgag541 uguaaaucau uugggcauga ugugcucaac cucacacgga acggguaugg caguacacag601 uacauuaggu ucagcccuga cuucacauuc ggguuugaag aaagucuuga agucgauacc661 aauccucuuc ugggcgccgg caaguucgcg acagauccgg cagugacucu cgcucaugag721 uuaauucacg ccgaacaccg gcuguauggu aucgcuauua auccaaaccg aguuuuuaaa781 gugaacacua acgcauacua cgagaugagc ggucucgagg ugagcuucga agaacuuaga841 accuuuggcg gacaugaugc uaaauucauu gauucacuuc aggaaaacga guuucgauua901 uacuacuaca acaaauuuaa agauguugca uccacacuua auaaagccaa gagcaucauc961 gguaccacug cgaguuugca guauaugaag aauguauuua aagagaagua cuugcucucc1021 gaagacacgu caggaaaauu cucugucgac aagcugaaau ucgacaagcu guauaaaaug1081 cugaccgaga uauacacgga ggacaacuuc gugaauuucu ucaaggucau caauaggaag1141 accuaccuga acuucgacaa agcuguguuu agaauaaaca uuguacccga cgagaacuau1201 accauuaagg acggcuucaa ccugaagggc gcaaaucugu cuaucaauuu uaauggacag1261 aauacugaga ucaacucccg caauuuuacc agguugaaaa acuuuacagg gcucuucgaa1321 uucuauaagc ugcuaugcgu gcgcggaauc auuccuuuua agugagcggc cgcuuaauua1381 agcugccuuc ugcggggcuu gccuucuggc caugcccuuc uucucucccu ugcaccugua1441 ccucuugguc uuugaauaaa gccugaguag gaagaaaaaa aaaaaaaaaa aaaaaaaaaa1501 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa1561 aaaaaaaaaa aaaaSEQ ID NO: 99, RNA, Clostridium botulinum, light chain botulinum, UPI000290BDD51 gaggaaauaa gagagaaaag aagaguaaga agaaauauaa gagccaccau gcccuucgua61 aacaaacaau uuaacuacaa ggauccaguc aauggcguug auauugcuua caucaagauc121 ccaaacgccg ggcaaaugca gccggugaaa gcuuucaaga uucacaauaa gauuugggug181 auuccugaaa gggacacauu cacaaauccc gaagaggggg accuaaaccc ccccccagaa241 gcaaagcagg ugcccguguc auauuaugac ucaaccuacc ugucuacaga uaacgaaaaa301 gauaauuauc ugaagggagu uacuaaacuc uuugaaagga uauauucuac ugaccucggc361 cgcaugcugc ucaccuccau uguaagaggg auacccuuuu ggggaggcag caccauagac421 accgagcuca aggucauaga cacaaauugc auuaacguga uccagccuga cggcuccuau481 cggagcgagg aauugaaucu cguaaucauu gguccaucag ccgauaucau ucaauuugag541 uguaaaagcu uugggcauga cguccuaaau uugacacgca auggauaugg guccacucag601 uacaucaggu ucucaccaga uuucaccuuc ggcuuugagg aaagccucga gguggacacg661 aauccucuuu ugggcgcagg caaguuugcu acggauccug cggugacucu ggcucacgag721 uuaauccaug ccgaacaucg acuguacgga aucgcaauca acccuaauag agucuucaag781 gugaacacca acgccuacua ugagaugagu ggguuggaag uuucguuuga agaacugcgg841 acauucgggg gucacgacgc gaaauucaua gacagucuuc aggagaauga guuuaggcug901 uauuacuaca acaaauuuaa agacguugcc agcacacuga auaaagccaa aaguaucauc961 ggcacuaccg cuagccucca guauaugaag aaugucuuca aggagaagua cuugcuuucu1021 gaggauaccu ccggcaaguu uucuguggac aaacugaagu uugauaagcu guacaagaug1081 cugacggaga uuuauaccga ggauaauuuc gugaacuucu uuaagguuau uaaucgcaaa1141 acuuaccuua acuucgacaa ggcaguguuc cgaauaaaca ucgucccgga ugagaauuac1201 acaaucaaag auggauucaa ccugaaagga gccaaccuga guaucaacuu uaacggucag1261 aacaccgaga ucaacucccg gaacuucacu agauuaaaga auuuuaccgg auuauucgaa1321 uucuacaagc ugcuuugcgu gcgugguauu auuccuuuua aaugagcggc cgcuuaauua1381 agcugccuuc ugcggggcuu gccuucuggc caugcccuuc uucucucccu ugcaccugua1441 ccucuugguc uuugaauaaa gccugaguag gaagaaaaaa aaaaaaaaaa aaaaaaaaaa1501 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa1561 aaaaaaaaaa aaaaSEQ ID NO: 100, RNA, Clostridium botulinum, light chain botulinum, UPI000290BEB 11 gaggaaauaa gagagaaaag aagaguaaga agaaauauaa gagccaccau gcccuuugua61 aacaaacagu uuaacuauaa ggaucccguu aacggcgucg acauagcuua uauuaagauc 121 ccuaaugccg gccagaugca gcccgugaag gcuuucaaaa uccauaacaa gauuuggguc 181 auuccggagc gagacacguu uaccaaccca gaagaaggcg aucugaaccc gcccccagag 241 gcaaagcagg ucccagucuc auauuacgau ucuaccuauc ugagcacaga uaacgagaag 301 gauaauuacc ugaagggagu uacaaaguug uuugaacgua ucuaucugac ugaccucggc 361 cgaauguuac ucacuuccau cgugcgcggc auuccauucu gggggggauc aacaaucgac 421 acugaguuga aaguaaucga caccaacugu aucaacguga uucaaccuga uggaucuuac 481 aggucagaag agcugaaccu agugaucaua ggcccuagug cggacauuau acaauucgag 541 ugcaaguccu uugggcauga cgugcucaau cugacacgga auggguacgg uucgacccaa 601 uauauccggu uuucuccaga cuuuaccuuc ggcuucgagg agagccuuga gguagacacg 661 aauccccucu uaggugccgg aaaauucgca accgaccccg cuguuacucu cgcacacgaa 721 cucauccacg cggagcacag acuguacggc auugccauua auccuaaucg cguuuucaag 781 gugaauacca augcuuacua ugagaugagu ggauuagaag uuuccuuuga ggagcugcgg 841 acuuucggug ggcaugaugc caaauucauu gauagcuugc aggagaacga auucagacuu 901 uacuacuaua acaaguucaa agauguggcc ucaacccuaa auaaggccaa aagcauaauc 961 gggacaacug cuagcuugca guacaugaaa aauguguuua aggaaaaaua ucuccuuucc 1021 gaagacacca gugggaaauu cagcgucgau aagcugaagu ucgacaaacu guauaaaaug 1081 cugacagaaa ucuacacaga ggacaauuuc gucaacuuuu uuaaggugau caauaggaaa 1141 acuuaccuua auuucgauaa agccguguuu aggaucaaca uugugccuga ugaaaacuac1201 acaauuaagg acgguuucaa ccuuaagggc gcaaaccugu cuacuaauuu uaaugggcag1261 aauaccgaga uaaacuccag aaacuucacc cgccugaaga acuuuacggg acuguuugaa1321 uuuuacaaac uguugugcgu gaggggaauu aucccuuuca agugagcggc cgcuuaauua1381 agcugccuuc ugcggggcuu gccuucuggc caugcccuuc uucucucccu ugcaccugua1441 ccucuugguc uuugaauaaa gccugaguag gaagaaaaaa aaaaaaaaaa aaaaaaaaaa1501 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa1561 aaaaaaaaaa aaaaSEQ ID NO: 101, RNA, Clostridium botulinum, light chain botulinum, UPI00005B712C1 gaggaaauaa gagagaaaag aagaguaaga agaaauauaa gagccaccau gccguuuguc61 aacaaacccu uuaauuauag ggauccugga aacggcguag acaucgcaua uaucaagauc121 ccuaacgccg gucagaugca gcccgucaag gccuucaaga uacaugaagg cguguggguc181 auccccgagc gagacacguu caccaauccc gaggaggggg aucugaaucc uccaccggaa241 gcaaaacagg ucccaguuuc uuauuaugac agcacauacu uaagcacuga uaacgaaaag301 gauaauuacc ugaaaggcgu uauaaaauug uucgaccgaa ucuacagcac cggucugggc361 cguaugcugc ugucguuuau ugucaagggc auccccuucu ggggugggag cacaauagac421 acugaguuga aggucaucga uacgaacugc aucaauguua uugaaccagg uggauccuau481 agaucugagg agcugaaccu cgugauuaca ggaccgucag cagacaucau ccaauuugag541 uguaaauccu uuggucacga cguauucaau cuaacuagaa acggguaugg cucaacacag601 uauauaaggu uuuccccuga cuucacauuu ggauucgaag agucacuuga gguagauaca661 aacccacugu uaggggcagg aaccuuugcu acagacccag cuguuacucu ggcccacgaa721 cuuauccaug cugcgcacag acuguacgga auugcuauca acccaaaccg cguguuaaaa781 gugaaaacua acgccuacua cgagaugucu ggccuugagg ugaguuuuga agaguugagg841 accuucggcg gcaacgauac aaacuucauu gacagucucu ggcagaagaa guuuagcaga901 gacgccuacg auaaucucca gaauauugcc cguauccuca augaagccaa gaccauuguu961 ggcaccacga cuccccucca guacaugaaa aauaucuuua uucgcaagua uuucuugucc1021 gaggaugcgu ccgggaaaau uucagugaac aaagccgcau ucaaggaguu cuaccgcgug1081 cucacccgcg gauuuacuga acuggaguuu gugaaccccu uuaaggugau uaaccggaag1141 accuaccuaa auuucgauaa agcuguguuc aggauaaaca ucgugccuga cgaaaacuau1201 accauaaaug agggcuuuaa ucuggaagga gcuaacucua augggcaaaa uacugaaauu1261 aacagucgga auuucacccg gcucaaaaau uucaccgggc uguucgaguu cuacaagcug1321 cuuugcgugc gggggaucau uccuuuuaag ugagcggccg cuuaauuaag cugccuucug1381 cggggcuugc cuucuggcca ugcccuucuu cucucccuug caccuguacc ucuuggucuu1441 ugaauaaagc cugaguagga agaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa1501 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa1561 aaSEQ ID NO: 102, RNA, Clostridium botulinum, light chain botulinum, UPI00016DBC111 gaggaaauaa gagagaaaag aagaguaaga agaaauauaa gagccaccau gccguuuguc61 aauaagcagu uuaauuaucg ggauccaguu aaugggguug auauagcaua uauuaagaua121 ccuaacgccg gucagaugca gccagugaag gcauucaaaa uucacgaggg aguuugggug181 auacccgaga gggauacauu caccaacccc gaggagggcg accuaaaccc cccuccagag241 gcuaaacagg ucccugucag cuacuacgac uccacuuacc uuagcacuga uaacgaaaag301 gacaacuauc ugaagggcgu caucaaacuu uuugauagga ucuacaguac aggccucggg361 agaaugcucc uaagcuuuau uguaaaggga aucccguuuu ggggcgguuc aaccaucgau421 acagagcuga agguaaucga uacaaauugc aucaauguga uugaaccugg cgguuccuau481 cguagugaag agcuuaaucu ggucauuacc ggacccucug ccgauauuau ucaguucgag541 ugcaaauccu uuggccauga cguguuuaau uugacccgca auggcuacgg cucuacucaa601 uacauccgcu ucucaccuga cuucaccuuc ggauucgaag aaagccugga aguggauacc661 aauccacucc ucggggcagg gaccuucgca accgacccag cuguuacccu ggcacacgaa721 cugauccaug cggcucaccg auuguacgga aucgccauca auccaaaccg cguucugaag781 gugaaaacaa acgccuauua cgagaugagu ggguuagagg uguccuuuga ggaacugcga841 acuuucggug gaaaugacac aaacuucauc gacucauuau ggcaaaagaa guucucucgu901 gacgccuacg auaaccucca gaacauagcc agaauccuga acgaagcuaa aaccauugug961 gggacaacua cgccccugca guauaugaaa aauauauuca uucggaaaua uuuuuugucg1021 gaggacgcgu ccggcaagau aucugugaac aaagcugcuu uuaaagaauu cuauagggug1081 uugacucggg gauuuacgga acuggaguuc gugaauccuu uuaaagugau caaucggaag1141 acuuaccuua auuuugacaa agccgucuuu cgcaucaaca ucguccccga cgagaauuau1201 acgauuaacg agggguucaa ccucgaggga gccaauucaa acgggcaaaa caccgagauc1261 aacagcagga acuuuacuag auuaaagaac uucacaggcc ucuucgaauu uuacaagcug1321 cuguguguaa gagguauuau ucccuucaag ugagcggccg cuuaauuaag cugccuucug1381 cggggcuugc cuucuggcca ugcccuucuu cucucccuug caccuguacc ucuuggucuu1441 ugaauaaagc cugaguagga agaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa1501 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa1561 aaSEQ ID NO: 103, RNA, Clostridium botulinum, light chain botulinum, UPI000290C3D01 gaggaaauaa gagagaaaag aagaguaaga agaaauauaa gagccaccau gcccuucguu61 aacaaacaau ucaacuacag agacccagug aauggggucg acaucgcuua cauaaagauc121 ccuaacgccg gacagaugca accagugaag gccuucaaaa uccaugaagg uguguggguu181 aucccagaaa gagauaccuu uacaaacccc gaggagggcg aucugaaccc gcccccagag241 gcaaagcagg ugcccguaag cuauuaugau aguaccuacc uuagcacaga uaaugagaag301 gacaauuacc ucaaaggagu caucaagcug uucgaccgca uuuauucaac agguuugggg361 cggaugcugc uuucauuuau ugucaagggg aucccuuucu ggggaggcag cacuauugac421 acugaacuga aagugaucga uacuaauugu auaaauguga uugagcccgg cgggucuuau481 cgcucugaag aacugaacuu aguuauuaca gguccuuccg cugacaucau ucaguuugaa541 ugcaagagcu uugggcacga cguguuuaac cucacucgca acggguacgg aucaacccag601 uauaucaggu uuagcccaga cuuuacguuu ggguucgagg agucucucga agucgauacc661 aacccguugc uuggagccgg cacauuugcg acggauccug cuguuacccu ugcccaugag721 cucauucacg cugcacaccg acuguauggu aucgcgauua aucccaauag agugcugaaa781 guaaaaacga acgcuuacua ugagaugucc ggcuuagaag ucuccuucga ggaacuaagg841 acuuucggcg gcaaugauac caauuuuauc gacucuuuau ggcagaagaa guucucaagg901 gaugccuacg acaaucugca gaacauagcc cggaucuuga augaggccaa gaccauugua961 ggcaccacua ccccgcugca guacaugaaa aauaucuuua ucagaaaaua cuuucucucc1021 gaggacgcau cggguaagau cagugugaau aaaccugcau ucaaggaguu cuaccgcguu1081 cugacuaggg gauucaccga gcuggaauuu gucaacccuu ucaaagugau aaaucguaaa1141 accuaccuca acuuugacaa agccgucuuc cggauuaaca uagugcccga ugagaacuau1201 acaaucaacg aaggauucaa ccuagagggc gcaaauucca acggacaaaa cacagaaaua1261 aauagucgga acuucacacg acucaagaau uucacugggc uguuugaguu cuauaagcug1321 uugugcgugc guggcauuau uccauuuaag ugagcggccg cuuaauuaag cugccuucug1381 cggggcuugc cuucuggcca ugcccuucuu cucucccuug caccuguacc ucuuggucuu1441 ugaauaaagc cugaguagga agaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa1501 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa1561 aaSEQ ID NO: 104, RNA, Clostridium botulinum, light chain botulinum, UPI00005B712D1 gaggaaauaa gagagaaaag aagaguaaga agaaauauaa gagccaccau gccucucguc61 aaccagcaaa uuaauuauua cgacccaguc aacggcguag acaucgcaua uaucaagauu 121 cccaaugccg gcaagaugca acccgugaaa gccuuuaaga uccacaacaa ggugugggug 181 auccccgaac gggacauuuu cacgaaccca gaagaggugg auuugaaucc gcccccugaa 241 gcuaagcaag uuccuauuuc auacuacgac ucagcauacc ugagcaccga uaacgagaaa 301 gacaacuauc ucaaaggcgu gauuaagcug uuugagagaa ucuacagcac cgaucugggg 361 cgaaugcuac ucauauccau cguccgggga aucccauucu ggggaggagg aaagauugac 421 acugaacuga aagugaucga uacaaauugc auuaacauua uccagcucga cgauaguuau 481 agaucggaag aguugaaccu ugccaucauu ggcccguccg cgaauauuau ugaaagccag541 uguucuuccu uccgcgacga cgugcugaau cugacucgga acggcuacgg cucuacgcag 601 uauauuaggu uuucaccuga uuucaccguc ggguuugaag aaucucugga ggucgacaca 661 aacccucucc ugggggcggg aaaauuugcu caggaucccg ccguugcccu ggcccaugag 721 cucauucacg ccgagcauag gcuuuauggu aucgcuauaa auacaaauag agucuucaaa 781 guaaacacga acgcauauua ugagauggcg gggcuugagg uuucccuuga ggaguugauc841 acuuuuggug gaaacgacgc uaaguucauc gacagccugc agaaaaaaga auucucucug 901 uauuacuaca auaaguuuaa agauaucgca uccacuuuaa auaaggccaa gagcauugug 961 gggaccacag ccucacuuca guacaugaaa aaugucuuca aggagaagua ccuccugagu 1021 gaggaugcca cuggcaaguu ucugguggau cgacugaagu ucgaugagcu auacaagcug 1081 cugaccgaaa ucuauacaga agacaacuuc gugaaauucu uuaaaguuuu aaaccgcaag 1141 acauacuuga auuucgauaa agcuguuuuc aagaucaaua uaguaccaga cgugaacuau 1201 acuauccacg auggcuuuaa ucuuaggaau accaaccuag cagcuaauuu caacggucag 1261 aacauagaga ucaacaauaa gaauuuugac aaguuaaaaa acuucaccgg uuuguuugag 1321 uuuuacaaac uccugugcgu gcgugggaua auaaccagua agugagcggc cgcuuaauua 1381 agcugccuuc ugcggggcuu gccuucuggc caugcccuuc uucucucccu ugcaccugua 1441 ccucuugguc uuugaauaaa gccugaguag gaagaaaaaa aaaaaaaaaa aaaaaaaaaa 1501 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 1561 aaaaaaaaaa aaaaSEQ ID NO: 105, RNA, Clostridium botulinum, light chain botulinum, UPI00019DB8851 gaggaaataa gagagaaaag aagagtaaga agaaatataa gagccaccat gcccttcgtg61 aauaaacagu ucaauuauaa ugacccugaa aaugguguag acauugccua cauuaagauc 121 ccuaaugcgg gaaagaugca gccugugaaa gcguucaaga uccauaacaa gguguggguu 181 aucccagaac gcgacauauu uaccaauccu gaagaagugg aucucaaccc cccaccagag 241 gccaaacaag ucccuauaag uuauuaugac ucggcuuacc ucucaacuga uaacgagaag 301 gauaacuacc ugaagggggu aauuaaacug uuugagcgaa ucuacagcac cgaucucggu 361 aggaugcuuc uuauaagcau ugugcgaggc auuccauuuu gggggggcgg aaaaaucgac 421 acagaauuga aggucaucga uacuaauugc aucaacauaa uucaacugga cgauuccuau 481 cggucugagg agcugaaucu ggccaucauc ggccccuccg ccaauaucau ugagucucag 541 ugcuccucuu ucagagacga uguccugaau uuaacuagaa acggcuacgg aaguacccag 601 uacauaaggu ucucacccga cuuuacaguu ggauuugagg aaucauuaga ggucgacacc 661 aacccgcugc ucggggcugg aaaauuugca caggaccccg ccguggcucu ugcucacgag721 cuuauccaug cagaacaccg ccuguacggg auugcaauca auacaaaccg ggucuucaag 781 gugaauacca augccuauua cgaaauggca ggccuggagg uuucuuugga ggaguugauu 841 acuuuugggg guaacgaugc uaaauuuauc gacucccugc aaaagaaaga guucucacug 901 uacuauuaca auaaguucaa ggacauugcg uccacguuga auaaggcuaa gaguaucgug 961 ggcacgacug ccagccugca guauaugaag aauguauuca aagaaaagua ucuacucagc 1021 gaggacgcca cgggaaaauu ucucguugau agacucaaau ucgaugaacu auacaagcug 1081 cugaccgaaa uuuauaccga agauaacuuc gucaaauuuu uuaaaguucu gaaccguaag 1141 accuaucuca acuucgacaa agccguguuu aagaucaaca uugugccgga cgugaauuac 1201 acaauccacg auggcuuuaa ccuacggaac acuaacuugg cagccaacuu caaugggcag 1261 aauauugaga ucaacaacaa aaacuuugau aagcugaaga acuucacagg ucuguucgag 1321 uucuacaagu uacuuugugu gaggggcauc auaacaagca aaugagcggc cgcuuaauua 1381 agcugccuuc ugcggggcuu gccuucuggc caugcccuuc uucucucccu ugcaccugua 1441 ccucuugguc uuugaauaaa gccugaguag gaagaaaaaa aaaaaaaaaa aaaaaaaaaa 1501 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 1561 aaaaaaaaaa aaaaSEQ ID NO: 106, RNA, Clostridium botulinum, light chain botulinum, UPI0001AE7D6A1 gaggaaauaa gagagaaaag aagaguaaga agaaauauaa gagccaccau gcccuuugug61 aacaagcagu uuaacuacaa ggauccagug aauggggucg acaucgcgua caucaaaauu 121 cccaaugcag gccagaugca accagucaaa gcuuuuaaga uccacaacaa aauuugggua 181 auuccagaaa gagauacuuu caccaacccu gaagaggggg accugaaucc cccaccggaa 241 gccaaacagg uucccguguc uuauuaugac agcacguacc uuuccacaga uaacgagaag 301 gacaacuacc ugaagggcgu gacaaagcug uuugaacgca uauauucuac agaacuggga 361 aggaugcugc ucacuucaau ugugagggga aucccauucu ggggugguuc cacaaucgac 421 acagaacuga agguuauuga caccaauugc auaaacguga uccagccuga cggcagcuau 481 cggucagaag agcugaaucu cgugaucauc ggaccuagug cugacaucau ucaguucgag 541 uguaaguccu ucggacacga cgugcugaau cucaccagga acggguaugg caguacucag601 uauauaagau uuagccccga uuucacauuc ggguucgagg agucgcucga aguggauacc 661 aauccucuuu uaggugccgg gaaauucgcc accgauccgg cggugacccu ugcccaugag 721 cugauucaug ccggccaucg gcuauacggc auagcuauua accccaaccg aguauucaaa 781 gucaauacca augcauacua cgaaaugucu ggguuggagg uaaguuucga agagcuucgu 841 acauuugggg aacacgacgc aaaauuuauc gacagucugc aagagaacga auuccgccug 901 uacuauuaua auaaguucaa agauaucgcc agcacgcuga auaaagccaa aucaauuguu 961 ggaaccacug ccucuuugca auauaugaag aauguuuuua aggagaaaua ccucuuaagc 1021 gaggauacau ccggcaaguu uagcguugac aagcugaaau uugauaaguu guauaagaug 1081 cugaccgaga ucuacacuga ggauaacuuc gucaaauucu uuaaggugcu uaauagaaag 1141 acuuaccuca auuuugauaa ggcagucuuc aaaaucaaca ucgugccuga ggucaacuac 1201 acuauuuaug acggcuucaa cuuacgaaau accaacuugg cugcuaauuu uaauggccag 1261 aacacugaga uuaacaacau gaacuuuaca aaacugaaga auuucacggg ucuauucgag 1321 uuuuacaagc ucuugugcgu ccggggaaua aucaccucca agugagcggc cgcuuaauua 1381 agcugccuuc ugcggggcuu gccuucuggc caugcccuuc uucucucccu ugcaccugua 1441 ccucuugguc uuugaauaaa gccugaguag gaagaaaaaa aaaaaaaaaa aaaaaaaaaa 1501 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 1561 aaaaaaaaaa aaaaSEQ ID NO: 107, RNA, Clostridium botulinum, light chain botulinum, UPI000198BDAE1 gaggaaauaa gagagaaaag aagaguaaga agaaauauaa gagccaccau gcuuuucgug61 aauaagcagu uuaauuacaa ggaccccguc aacggugugg acauugccua caucaaaauc121 ccgaacgccg ggcagaugca accuguaaag gccuuuaaaa uucauaacaa gaucugggug181 auacccgaaa gagauacuuu caccaauccu gaggaaggcg accucaaucc cccaccugag241 gcuaagcaag ugccagucag cuauuaugac agcacuuauc uuucuaccga uaacgagaag 301 gauaacuauc ugaagggggu gacaaaacug uucgagcgaa ucuauaguac cgaacuuggu 361 cggauguugc ucaccagcau uguucgagga auuccauuuu ggggcgggag cacuauagac 421 acugagcuaa aaguuauuga cacaaacugc auuaauguga uccagcccga cggcucauac481 agaagugagg agcugaacuu gguuaucaua ggcccguccg cagauaucau ucaguucgag 541 uguaaaagcu ucggccacga cgugcucaac cugacucgga acggauacgg gaguacgcaa 601 uauauaaggu ucucaccuga uuuuacauuu gguuucgagg agucucugga ggucgauacu 661 aacccacugc uuggcgccgg gaaauucgcu accgauccag cugugacccu ggcccaugaa 721 cuaauucacg ccgggcacag guuauaugga aucgcaauca aucccaacag agucuuuaag 781 guaaacacca augccuacua cgaaaugagc gggcuggaag ucucuuuuga agaacuccgg 841 accuuuggag aacaugacgc aaaguucauc gauucucugc aggaaaacga auuccgccug 901 uacuacuaua auaaauucaa agacauugcc uccacauuga auaaagcgaa gucaauagua 961 ggcacaacag cuucacugca guacaugaag aacguuuuca aggagaagua ucuauugucc 1021 gaagauacau ccggcaaguu uucgguggac aaacucaagu uugacaaacu guacaagaug 1081 uuaacugaga ucuacaccga ggacaauuuu gugaaauucu uuaaaguucu caaucgcaaa 1141 accuacuuga auuuugauaa ggcagucuuu aagauuaaca ucgugccuga ggugaacuau 1201 acgaucuaug auggauucaa ccugaggaac acaaaucugg cggcuaauuu caauggucag 1261 aauaccgaga ucaacaauau gaacuuuacg aagcugaaga auuucacugg ccuuuucgag 1321 uucuacaaau uacucugcgu ccguggaauu aucacaucca agugagcggc cgcuuaauua 1381 agcugccuuc ugcggggcuu gccuucuggc caugcccuuc uucucucccu ugcaccugua 1441 ccucuugguc uuugaauaaa gccugaguag gaagaaaaaa aaaaaaaaaa aaaaaaaaaa 1501 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa1561 aaaaaaaaaa aaaaSEQ ID NO: 108, RNA, Clostridium botulinum, light chain botulinum, UPI0001B7D2511 gaggaaauaa gagagaaaag aagaguaaga agaaauauaa gagccaccau gccauuuguc61 aauaagcagu ucaacuacaa ggaucccguu aauggggucg auaucgccua caucaaaaua121 ccuaacgcug gacagaugca acccgugaag gccuucaaga uucauaauaa gauaugggug181 auacccgaaa gagauacauu cacuaauccu gaagagggcg accucaaccc accccccgaa241 gccaaacaag ucccugucuc guauuacgac agcacuuacu ugucuaccga caacgaaaaa301 gacaauuauc ucaagggagu gacuaagcuc uucgaacgua uuuauagcac ugaccugggc361 cgaaugcuuc ugaccucaau cguacgcggc auuccauucu ggggugggag cacgauugac421 acugagcuga aagugaucga uaccaacugc aucaauguaa uucagccgga uggaagcuac481 cgcucagagg agcucaaucu ggugaucauc gggccuucag cugauaucau ccaauuugaa541 uguaaaaguu ucggacauga aguccugaac cugacgcgga acggcuacgg cagcacucag601 uauaucagau ucagccccga cuuuaccuuc ggauuugagg agucucugga gguugauaca661 aacccauugu uaggcgcagg caaguucgcu acugauccgg cggucacacu ggcacacgag721 cuuauucacg caggccacag gcuauaugga auagccauaa acccuaaccg agucuuuaag781 guuaauacua acgcauacua ugaaaugucu ggucuggagg ugucauucga ggagcugaga841 accuuuggug gucaugaugc caaauucauu gauagucucc aggaaaacga guucaggcug901 uauuauuaca auaaguucaa agacauugcg uccacauuaa acaaagccaa auccaucgug961 gggacaaccg ccucuuugca guauaugaag aauguuuuua aagagaaaua cuuguugucc1021 gaggacacgu ccgggaaguu uaguguugac aagcugaagu uugauaagcu uuacaaaaug1081 cugaccgaga uuuauaccga agacaauuuc guaaaguucu uuaaagugcu caaccggaag1141 acauaucuaa auuuugacaa ggcaguguuc aaaaucaaua ucgugccaaa ggugaauuac1201 accaucuacg acggguucaa ccugcggaau acaaauuuag ccgcuaacuu caacggccag1261 aauacagaga ucaacaacau gaauuuugcu aaacucaaga acuuuaccgg acuguuugaa1321 uuuuacaagc uucuuugcgu gagggggauu auuaccucca aaugagcggc cgcuuaauua1381 agcugccuuc ugcggggcuu gccuucuggc caugcccuuc uucucucccu ugcaccugua1441 ccucuugguc uuugaauaaa gccugaguag gaagaaaaaa aaaaaaaaaa aaaaaaaaaa1501 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa1561 aaaaaaaaaa aaaaSEQ ID NO: 109, RNA, Clostridium botulinum, light chain botulinum, UPI000290B9951 gaggaaauaa gagagaaaag aagaguaaga agaaauauaa gagccaccau gccauuugug61 aacaagcagu ucaacuauaa ggaucccgug aacggagucg acauugcaua caucaagaua121 cccaacgcgg gccagaugca gccagucaag gcuuucaaaa uucacaauaa aauuugggug181 auucccgagc gcgauaucuu uaccaacccc gaagaggggg accucaaccc gccaccugag241 gcuaagcaag ucccuguguc auacuaugac agcacauacc ugucaaccga uaaugaaaaa301 gauaauuauu uaaagggcgu caccaagcug uucgagcgca ucuacucuac ggaccugggg 361 agaaugcucc uuaccagcau agugcgugga auuccauuuu ggggcgggag uacuaucgau 421 acagaacuga aaguuaucga cacuaauugc auuaacguga uacaaccuga cggcaguuau 481 aggagugagg agcucaacuu agucauuauc gguccuagcg ccgacaucau aaauuucgag 541 ugcaaaucuu uugggcacga cguacugaac cugacaagga acggauaugg cuccacucag 601 uacauccggu ucucaccuga cuuuacauuc ggguucgagg agucauugga aguggacacc 661 aacccacugc uaggcgcugg uaaauuugcc auugaccccg ccgugacucu cgcacaugaa 721 cuuauccaug ccggucauag acuguacgga aucgccauaa auccgaaccg cguuuucaaa 781 gugaacacaa acgcguacua cgaaaugucc ggucuugagg ugucuuuuga ggaacuccgg 841 accuuuggcg gacacgaugc aaaguucauc gauucuuugc aggaaaacga auuccgauua 901 uauuauuaua acaaauucaa agagguugca uccauucuga auaaggccaa gagcauuauc 961 ggaacuaccg cuagccugca guacaugaag aauguguuua aagaaaagua ccugcugucc 1021 gaggauacuu cggggaaguu cagcguugac aaacugcggu ucgacaaacu uuauaagaug 1081 uugacugaga uuuacaccga agauaauuuc guuaaguucu uuaaagucuu gaauagaaag 1141 acauaucuaa acuuugauaa ggcuguguuu aaaaugaaca ucguacccga gguaaauuac 1201 acaauauacg auggguucaa ucuccgaaau accaaucugg ccgccaauuu caacggccag 1261 aauaccgaaa ucaacaacau gaauuuuacg aagcuuaaaa auuuuacagg acucuucgag 1321 uuuuauaagu ugcugugugu caggggcauc auuacgucca agugagcggc cgcuuaauua 1381 agcugccuuc ugcggggcuu gccuucuggc caugcccuuc uucucucccu ugcaccugua 1441 ccucuugguc uuugaauaaa gccugaguag gaagaaaaaa aaaaaaaaaa aaaaaaaaaa 1501 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa1561 aaaaaaaaaa aaaaSEQ ID NO: 110, RNA, Clostridium botulinum, light chain botulinum, UPI0003C9D2A11 gaggaaauaa gagagaaaag aagaguaaga agaaauauaa gagccaccau gcccuucguu61 aacaaacagu ucaacuauaa agacaccguu aacggcgugg acaucgcuua cauuaagauu121 ccaaaugcug gccagaugca gcccgucaaa gcuuucaaga uucauaauaa gaucugggug181 auuccugagc gugauacauu cacuaacccu aaggaaggag aucucaaccc cccgccagag241 gcaaaacaag uaccuguuuc uuacuacgau ucaacauauc ucagcacuga uaacgagaag301 gacaauuauc ugaagggcgu uacuaaauug uuugaaagga ucuacuccac ugacuugggu361 cgcaugcuuc ugacauccau cgugcggggc auuccauucu ggggcggauc aaccauugac421 acagaacuua aggugauuga uaccaacugu aucaacguga uccaacccga cgguuccuau481 cgcucggagg aguuaaaucu ggugaucauc gggcccagug ccgacaucau acaauuugaa541 ugcaagaguu uuggacauga cguccuaaac cuaacgagaa auggauacgg cucaacccag601 uauauacggu ucucucccga uuuuaccuuc ggguucgaag agagccugga gguggacacc661 aacccgcuuc ugggcgcagg caaauucgcc acugauccag ccgucacacu ggcucacgaa721 uuaauucacg ccgagcacag acucuacggg auugcgauaa auccuaaccg aguguucaag781 gucaauacca acgccuacua ugagaugagc ggucucgaag uuagcuuuga ggagcucagg841 accuucgggg gacauaaugc caaguucauc gauucucucc aggagaacga auuccgacug901 uacuacuaua auaaauuuaa agacauagcc agcaccuuaa auaaggcgaa guccauagua961 ggcacaaccg caucacugca guauaugaaa aacguguuua aggagaagua ccuuuugagc1021 gaagauacau ccggaaaauu cucugucgau aaguugaaau uugacaaacu guauaaaaug1081 cugacugaga ucuauacaga ggacaacuuc gugaaauucu uuaaggucuu gaauaggaag1141 acguaccuga auuuugauaa ggcaguguuc aaaaucaaua ucgugccuga ugaaaacuac1201 acgauuaagg acggguuuaa ccugaagaac acuaaucuug cugccaacuu uaaugggcag1261 aauaccgaaa ucaauaguag aaauuuuacu aagcucaaga acuucacagg gcuguuugag1321 uuuuacaaac ugcugugcgu acgggguauu aucccauuua aaugagcggc cgcuuaauua1381 agcugccuuc ugcggggcuu gccuucuggc caugcccuuc uucucucccu ugcaccugua1441 ccucuugguc uuugaauaaa gccugaguag gaagaaaaaa aaaaaaaaaa aaaaaaaaaa1501 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa1561 aaaaaaaaaa aaaaSEQ ID NO: 111, RNA, Clostridium botulinum, light chain botulinum, UPI000559A4691 gaggaaauaa gagagaaaag aagaguaaga agaaauauaa gagccaccau gccauucguu61 aacaagcagu ucaauuacaa ggauacaguu aacggcauug acauugcuua caucaagauu121 ccgaacgcag gacagaugca gcccgugaaa gcauucaaga uacauaacaa aaucuggguc181 auccccgaac gagauacauu cacaaacccc aaggaggggg accuaaaucc ccccccugag241 gccaagcaag ucccuguuag uuauuacgac uccacauacc ucuccaccga caaugaaaaa301 gauaacuauc uaaagggggu gaccaagcuc uucgagcgga ucuauagcac cgaucuuggg361 cggauguugc ugacuucuau cguaaggggg aucccguucu gggggggcuc aacaaucgau421 accgaacuga aagucaucga uacuaacugc aucaauguga uucagccuga cgguucauac481 agaucagagg aacugaaccu cgucauuauc ggaccaucug cugacaucau ucaauucgaa541 uguaagucuu uuggacauga cguguuaaau cuuaccagga acgguuacgg gucgacccag601 uacauacggu ucucucccga uuuuacuuuu gguuucgaag aguccuugga gguggacacc661 aauccacugc ugggcgccgg caaguuugcg acugauccug ccgugacccu ugcacaugag721 cugauucacg cggaacacag acuguauggc auugcaauca acccuaauag gguauuuaaa781 gucaacacca acgccuacua ugagauguca ggucuggagg ucuccuuuga ggaauugcga841 acguuuggcg gacacaacgc uaaguucauc gauagucucc aggagaacga auuucgucuc901 uauuauuaua auaaauuuaa agacauagcc agcacccuga acaaggcuaa gagcauagug961 ggcacaacag ccuccuuaca auacaugaag aauguguuua aagagaaaua ccugcuuagc1021 gaggacacua gcgggaaguu cagcguggac aaguugaaau uugacaaacu guacaaaaug1081 cuuacugaga ucuauaccga ggauaacuuc guaaaauuuu uuaaaguuuu gaaucgcaag1141 acuuaucuga auuucgacaa agccguguuc aaaauuaaua uugugccaga ugaaaauuac1201 acgauuaagg auggcuucaa ccugaagaac acaaaucucg ccgcuaauuu uaauggacag1261 aauacugaga uaaacaguag aaauuucacg aaacucaaga acuucacagg ccuguuugaa1321 uucuacaagc uguuaugcgu ucgcggaauu aucccauuua agugagcggc cgcuuaauua1381 agcugccuuc ugcggggcuu gccuucuggc caugcccuuc uucucucccu ugcaccugua1441 ccucuugguc uuugaauaaa gccugaguag gaagaaaaaa aaaaaaaaaa aaaaaaaaaa1501 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa1561 aaaaaaaaaa aaaaSEQ ID NO: 112, RNA, Clostridium botulinum, light chain botulinum, UPI0000001386-Protein1 gaggaaauaa gagagaaaag aagaguaaga agaaauauaa gagccaccau gccauucgua61 aauaagcaau ucaacuauaa agauccagua aauggcgugg acauugccua uauaaaaauc121 cccaacgcgg gacagaugca gccagugaag gcauucaaaa uccacaauaa aauaugggug 181 auucccgagc gggacacuuu cacaaacccc gaagaaggag aucucaaccc uccuccggag 241 gccaagcaag uaccggugag cuacuacgac aguaccuacc uguccaccga caacgagaaa 301 gauaacuauc ugaagggcgu cacaaaacuc uuugaacgca ucuacaguac ugaccuuggc 361 cggaugcuac ucacuucaau aguucgugga auccccuucu ggggcggcuc aaccaucgac 421 acggaauuga aagucauuga uaccaauugc aucaauguga uccagccaga cggauccuau 481 cgcagcgaag agcugaaucu cgugaucauu gguccuucug cugacauaau ccaguuugag 541 ugcaagucau ucgggcauga agugcucaac cugacacgaa acggcuacgg gagcacacag 601 uauauuagau ucagccccga uuuuaccuuu gguuucgaag agucucugga gguggauacc 661 aauccucugc ugggggcagg gaaguucgcu accgaucccg cggucacgcu cgcucaugag 721 uuaauucacg cagggcauag acucuauggg auugccauca acccuaacag gguuuuuaag 781 guuaauacaa acgcauacua ugaaaugagc ggccuugagg ugucguuuga ggagcugcgg 841 accuuuggug gacacgaugc uaaguuuaua gacucuuuac aggagaacga guuuagacug 901 uauuauuaca acaaguucaa agauaucgcc uccaccuuga auaaagccaa guccauuguc 961 ggcacuacag ccagucugca guacaugaag aacguuuuca aagaaaagua ccugcuauca 1021 gaggauacuu ccggcaaguu cagcgucgau aaguugaaau uugacaagcu guacaaaaug 1081 cugaccgaga uuuauacuga ggacaacuuu guuaaauuuu ucaaagugcu gaaccgaaag 1141 acuuauuuga acuuugacaa ggcugucuuu aagaucaaua uugugccaaa agugaauuac 1201 acaauuuacg acggauucaa ucuuaggaau acaaaucugg ccgccaauuu uaacggacaa 1261 aacacggaaa ucaacaauau gaauuucaca aaguuaaaga auuucaccgg gcuuuucgaa 1321 uucuacaaac uuuugugugu cagggguauc aucacuucua agugagcggc cgcuuaauua 1381 agcugccuuc ugcggggcuu gccuucuggc caugcccuuc uucucucccu ugcaccugua 1441 ccucuugguc uuugaauaaa gccugaguag gaagaaaaaa aaaaaaaaaa aaaaaaaaaa 1501 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 1561 aaaaaaaaaa aaaaSEQ ID NO: 113, RNA, artificial, Hall Strain Deactivated LC botulinum1 gaggaaauaa gagagaaaag aagaguaaga agaaauauaa gagccaccau gcccuucguc61 aauaaacagu uuaacuauaa ggauccugug aauggagugg acaucgccua uauaaaaaua 121 ccgaacgcug gacaaaugca accugugaaa gcuuuuaaga uacauaauaa gauuugggug 181 aucccugagc gugauacuuu cacaaauccu gaggaaggcg aucuuaaccc ucccccggag 241 gcuaaacagg uuccagugag cuacuacgac uccaccuauc uuuccaccga caacgagaag 301 gacaacuauc ugaagggggu gacuaaacuc uucgagagaa uuuacucaac cgaucugggc 361 cggauguuac ugaccucaau ugucagggga auccccuuuu ggggaggcuc uacuaucgau 421 acagaacuga aagucaucga uaccaacugc auuaacguua uacagcccga uggcaguuac 481 cgaagcgagg agcucaaccu gguuauuauc ggcccaagug cugauaucau ccaguucgag 541 uguaagucgu uugggcacga ggugcugaau cugacacgga auggauaugg gagcacgcaa 601 uacaucaggu uuagucccga uuucacuuuc ggcuucgagg agagccuuga gguggacacc 661 aauccauugu ugggggcagg caaguucgca acugacccag cuguuaccuu ggcgcacgcc 721 cugauucacg cuggccauag gcuguacggg aucgccauca acccaaaucg ggucuucaaa 781 guuaauacaa acgccuacua cgaaaugagc ggacuagaag ucucuuucga agcacuccga 841 acauuugggg gucaugacgc aaaguuuauc gacuccuugc aggaaaacga guuccgccug 901 uauuacuaua auaaguuuaa ggacaucgcc ucaacacuca auaaggccaa gucaauuguc 961 gguacgacag caucucuaca guauaugaag aauguauuua aagaaaagua ucuuuuaucc 1021 gaagacacua gcggcaaauu cuccguagac aaacucaagu uugacaagcu guauaagaug 1081 uuaacagaaa uuuacacaga agacaacuuu gugaaauucu uuaaaguguu gaacagaaag 1141 acuuaccuga acuuugauaa ggcgguguuc aagaucaaca uugugcccaa agucaacuac 1201 acgauauaug auggauuuaa ucugcgcaau accaaccucg ccgccaauuu caaugggcag 1261 aacaccgaaa ucaacaauau gaauuucacc aaacugaaaa acuucacugg ucucuucgag 1321 uuuuacaagc uucugugcgu aagagguauu auuaccucua aaugagcggc cgcuuaauua 1381 agcugccuuc ugcggggcuu gccuucuggc caugcccuuc uucucucccu ugcaccugua 1441 ccucuugguc uuugaauaaa gccugaguag gaagaaaaaa aaaaaaaaaa aaaaaaaaaa 1501 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 1561 aaaaaaaaaa aaaaSEQ ID NO: 114, RNA, artificial, expression mRNA- LC botulinum1 gggaaauaag agagaaaaga agaguaagaa gaaauauaag accccggcgc cgccaccaug61 caccaccauc accaccaccc uaagaucaac agcuucaacu acaacgaccc ugugaaugac121 agaacaaucc uguauaucaa gccaggcggc ugucaggagu uuuacaaaag cuuuaacauc 181 augaaaaaca ucuggaucau ccccgagagg aaugugauug gcacaacccc ucaggacuuc 241 cauccuccua ccagccugaa aaacggcgac agcagcuacu acgaccccaa cuaccugcag 301 agcgacgagg aaaaggaccg guuccugaaa aucguuacca agaucuuuaa uagaaucaac 361 aacaaccugu cuggaggaau ccugcuggaa gaacugagca aggccaaucc uuaucugggc 421 aacgacaaca ccccagauaa ucaauuccac aucggcgacg ccagcgccgu ggaaaucaag 481 uucuccaacg gcucucagga cauccugcuu ccuaacguca ucaucauggg cgcugaaccu 541 gaccuguucg agacaaauuc uagcaauauu agccugcgga acaacuacau gcccuccaac 601 cacagauucg gcagcaucgc caucgugacu uuuagcccug aauacagcuu uagauucaac 661 gauaacugca ugaacgaguu cauccaggau ccugcccuga cccugaugca cgagcugauc 721 cacagccugc acggccugua cggagccaag ggcaucacca ccaaguauac aaucacacag 781 aagcagaacc cucugaucac aaacauuaga ggcaccaaca ucgaggaauu ccugaccuuc 841 ggcggaacag accugaacau caucaccagc gcccagagca augauaucua caccaaccug 901 cuggccgacu acaaaaagau ugccucuaag cugucaaaag ugcagguguc caacccccug 961 cugaaccccu acaaggacgu guucgaggcu aaguacggcc uggauaagga ugcuagcggc 1021 aucuacagcg ugaacaucaa caaguucaau gauaucuuca agaagcugua cucuuucacc 1081 gaguucgacc ugcggaccaa guuucagguc aagugcagac agaccuacau cggacaauac 1141 aaguacuuca agcuuucuaa ucugcucaac gacagcaucu acaacaucuc cgagggcuac 1201 aauaucaaca aucugaaggu gaacuuccgg ggccagaacg ccaaccugaa ccccagaauc 1261 aucaccccaa ucacagggag aggccuggug aagaaaauca uccgcuucug caagaacauc 1321 gugucuguga agggcaucag auaagcugga gccucggugg ccuagcuucu ugccccuugg 1381 gccucccccc agccccuccu ccccuuccug caccguaccc ccgugucuuu gaauaaaguc 1441 ugagugggcg gcaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 1501 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaSEQ ID NO: 115, RNA, artificial, expression-mRNA-LC C light chain botulinumgggaaauaag agagaaaaga agaguaagaa gaaauauaag accccggcgc cgccaccaug61 caccaccacc accaccaucc uaucacaauc aacaauuuca acuacucuga uccugucgau121 aacaagaaca uucuguaucu ggauacacac cugaacaccc uggccaauga gccugagaag 181 gccuuccgga ucaccggcaa caucuggguc auccccgaca gauucagcag aaacucuaac 241 cccaaccuga acaagccccc cagagugacc uccccuaaga gcggauauua cgacccuaac 301 uaccugucua cagauagcga caaggacacc uuucugaagg aaaucaucaa gcuguucaag 361 cggaucaaca gcagagaaau cggcgaggag cugaucuacc ggcugucuac cgauauccca 421 uuccccggaa acaacaacac cccuaucaac acauuugauu ucgacgugga cuucaacagc 481 guggacguga aaaccagaca gggcaauaac ugggugaaga ccggcagcau caauccuagc 541 gugaucauca ccggccccag agagaacauu aucgauccug agacaagcac cuucaagcug 601 accaacaaca cauucgccgc ccaggagggc uucggcgccc uaagcaucau cagcauuucu 661 ccuagauuca ugcugaccua cuccaaugcc acaaacgacg ugggcgaggg aagauucagc 721 aagagcgagu ucugcaugga ccccauccug auccugaugc acgagcugaa ccacgccaug 781 cacaaccugu acggcaucgc caucccuaau gaccagacca ucagcucagu gacaagcaac 841 aucuucuaca gccaguacaa cgugaagcug gaauacgccg agaucuaugc uuuuggcgga 901 ccuacaaucg accugauccc uaaguccgcc aggaaguacu ucgaggaaaa agcucuggac 961 uacuacagaa gcaucgcuaa aagacugaau agcaucacca ccgccaaccc aucuagcuuc 1021 aacaaauaca ucggcgaaua uaagcagaag cucauccgga aguaccgcuu uguuguggaa 1081 agcagcggcg aggugaccgu gaaccggaac aaguucgugg aacuguacaa cgagcugaca 1141 cagaucuuca ccgaguuuaa uuacgccaag aucuacaacg ugcagaauag aaaaaucuac 1201 cugagcaaug uguacacccc ugugaccgcc aacauccugg acgacaacgu guacgacauc 1261 cagaacggcu uuaacauccc uaagucgaac cugaacgugc uguuuauggg ccaaaaccuc 1321 ucccggaacc cagcccugag aaaagugaac ccugaaaaca ugcuguaccu guucaccaag 1381 uucugucaca aggcuauaua agcuggagcc ucgguggccu agcuucuugc cccuugggcc 1441 uccccccagc cccuccuccc cuuccugcac cguacccccg ugucuuugaa uaaagucuga 1501 gugggcggca aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 1561 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaaSEQ ID NO: 116, RNA, artificial, expression_mRNA_LC_A2 light chain botulinum 1 gggaaauaag agagaaaaga agaguaagaa gaaauauaag accccggcgc cgccaccaug61 caccaccacc accaucaucc uuuugugaac aagcaguuca acuacaaaga uccugugaac121 gguguugaca ucgcuuacau caagaucccc aacgccggcc agaugcagcc cguuaaggcc 181 uucaagaucc acaacaagau cugggugauc cccgagagag auacauuuac aaauccugaa 241 gaaggcgauc ugaacccucc uccagaagcc aaacaggugc cugucuccua cuacgacagc 301 accuaccugu cuaccgauaa cgagaaggau aacuaccuga aaggcgugac caagcuguuu 361 gaacggaucu acagcacaga ccugggcaga augcugcuca ccagcaucgu gcggggcauc 421 ccuuucuggg gcggcucuac caucgacaca gaacugaagg ugaucgacac caacuguauc 481 aaugugaucc aaccugaugg cagcuacagg agcgaggagc ugaaucuggu gaucaucgga 541 ccuagcgccg auaucauuca auuugaaugc aaguccuuug gccacgacgu ccugaaccug 601 acacggaacg gauacggaag cacacaguac aucagauuca gcccugacuu caccuucggc 661 uucgaggaau cccuggaagu ggacaccaau ccucugcugg gcgcuggcaa guucgccacc 721 gaccccgccg ucacacuggc ccacgagcuc auccacgccg agcacagacu guacggcauc 781 gccaucaauc ccaauagagu guucaaggug aacaccaacg ccuacuacga gaugagcggc 841 cuggaggugu ccuucgagga gcugcgcacc uucggcggac acgacgccaa guucaucgac 901 agccugcagg agaacgaguu ccggcuguau uauuacaaca aauucaaaga cguggccucu 961 acccugaaca aagcuaaaag caucaucggc acaacagcca gccugcagua caugaagaac 1021 guguucaagg aaaaguaccu gcugucugag gacaccagcg gaaaguucag cguggacaag 1081 cugaaguuug acaagcugua caagaugcug accgagauuu acaccgaaga uaauuucgug 1141 aacuucuuua aggugaucaa cagaaagacu uaccugaacu uugauaaggc uguguucaga 1201 aucaacaucg ugcccgacga gaacuauacc aucaaggacg gcuucaaucu gaagggcgcc 1261 aaccugagca ccaacuucaa cggccagaac acagagauca acagcagaaa cuucaccaga 1321 cugaaaaacu ucaccggccu guucgaguuc uacaagcugc ugugcgugcg gggcaucauc 1381 ccauucaagu aagcuggagc cucgguggcc uagcuucuug ccccuugggc cuccccccag 1441 ccccuccucc ccuuccugca ccguaccccc gugucuuuga auaaagucug agugggcggc 1501 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa1561 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aSEQ ID NO: 117, RNA, artificial, expression mRNA_LC_Al_Hall_Neg light chain botulinum1 gggaaauaag agagaaaaga agaguaagaa gaaauauaag accccggcgc cgccaccaug61 caccaccacc aucaccaccc cuuugugaac aagcaguuua auuacaaaga ccccguuaau121 ggcguggaca ucgcuuacau caagaucccu aaugccggcc agaugcagcc ugugaaggcc181 uucaagaucc acaacaaaau cugggucauc ccagagcggg acaccuucac caaucccgaa241 gagggcgacc ugaacccucc uccagaggcc aagcaggugc cugugucuua uuaugauucu301 accuaucuga gcaccgacaa ugagaaggau aauuaccuga agggcgugac caagcuguuu361 gaacggaucu acagcaccga ucugggaaga augcugcuga caagcaucgu cagagggauc421 cccuuuuggg gcggcagcac caucgacacc gagcugaagg ugaucgacac aaacuguauu481 aaugugaucc aaccugacgg cagcuacaga ucugaagaac ugaaccuggu gaucauugga541 ccuuccgccg acaucaucca guucgagugc aagagcuucg gccacgaggu gcugaaccug601 acaagaaacg guuauggcuc aacccaguac aucagauuca gcccugauuu cacauucgga661 uucgaggaaa gccucgaggu ggacaccaac ccucugcugg gcgccggcaa auucgccaca721 gauccugccg ugacccuggc ccaccagcug aucuacgccg gccacagacu guacggcauc781 gccaucaacc ccaacagagu guucaaggug aacaccaacg ccuacuacga gaugagcggc841 cuggaagugu ccuucgagga gcugaggacc uuuggaggcc acgacgccaa auucaucgac901 agccugcagg aaaacgaguu cagacuguac uacuacaaca aguucaaaga uaucgcaagc961 acacugaaca aagccaaguc caucgucgga acaacagccu cucugcaaua caugaagaac1021 guguucaagg aaaaguaccu gcugagcgag gacacaagcg gaaaguucag cguggauaaa1081 cugaaguucg acaagcucua caagaugcug accgagaucu acaccgaaga uaacuucgug1141 aaauucuuca aggugcugaa ccgcaagacc uaccugaacu uugacaaggc uguguucaag1201 auuaacaucg ugcccaaggu gaacuacacc aucuacgacg gcuucaaccu gcggaacacc1261 aacuuggcug cuaauuuuaa cggccagaac acagaaauca acaacaugaa cuucacuaag1321 cugaagaacu uuaccggccu guucgaguuc uacaagcugc ugugcgugcg gggcaucauc1381 accagcaagu aagcuggagc cucgguggcc uagcuucuug ccccuugggc cuccccccag1441 ccccuccucc ccuuccugca ccguaccccc gugucuuuga auaaagucug agugggcggc1501 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa1561 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aSEQ ID NO: 118, RNA, artificial, expression mRNA LC Al Hall light chain botulinum1 gggaaauaag agagaaaaga agaguaagaa gaaauauaag accccggcgc cgccaccaug61 caccaccacc accaccaucc uuucgugaac aagcaguuca acuacaaaga uccugugaac121 ggcguggaca ucgcuuacau caagaucccc aacgccggcc agaugcagcc ugugaaggcc181 uucaaaauuc acaacaaaau cugggugauc cccgagagag auacauucac caauccugagf241 gaaggcgacc ugaacccacc uccugaggcc aaacaggugc cuguuucuua cuaugauagc301 acuuaccuga gcaccgauaa ugagaaggac aacuaccuga aaggcgugac caagcuguuu361 gagcggaucu auucuaccga ccugggcagg augcugcuga caagcaucgu gcggggcauc421 ccauucuggg gcggcagcac aaucgauacc gagcugaagg ugaucgacac aaacugcauc481 aacgugaucc aaccugaugg cucuuauaga agcgaggaac ugaaccuggu cauuauagga541 ccuuccgccg acaucaucca guuugaaugu aaaagcuucg gccacgaggu gcugaaucug601 acaagaaaug gcuacggcag cacacaguac aucagauuca gcccugacuu caccuucggu661 uucgaggaaa gccuggaagu ggacaccaac ccccugcugg gcgccggaaa auucgccaca721 gaccccgccg ugacacuggc ccacgagcug auccacgccg gccauagacu guacggaauc781 gcaaucaauc cuaacagagu guucaagguc aacaccaacg ccuacuacga gaugagcggc841 cuggaaguuu ccuucgagga gcugcgcacc uucggaggcc acgacgcuaa guucaucgac901 agccugcagg agaacgaguu cagacuguac uacuacaaca aguucaagga caucgccucu961 acccugaaca aggccaaguc caucgugggc accaccgcca gccugcaaua caugaaaaac1021 guguucaagg aaaaguaccu gcuuucugaa gauacauccg gcaaguuuag cguggauaag1081 cugaaguucg acaagcugua caagaugcug accgaaaucu acaccgagga caacuucgug1141 aaguucuuca aggugcugaa ccggaagacc uaccugaauu uugacaaagc uguguucaag1201 aucaacaucg ugcccaaggu gaauuacacc aucuacgacg gcuuuaaccu gagaaacaca1261 aaccucgccg cuaauuucaa cggccagaac accgagauca acaacaugaa cuuuacaaag1321 cugaagaacu ucaccggacu guucgaguuc uacaagcucu ugugcgugcg gggcaucauc1381 accagcaagu aagcuggagc cucgguggcc uagcuucuug ccccuugggc cuccccccag1441 ccccuccucc ccuuccugca ccguaccccc gugucuuuga auaaagucug agugggcggc1501 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa1561 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aSEQ ID NO: 119, RNA, artificial, expression mRNA_mGreenLantern1 gggaaauaag agagaaaaga agaguaagaa gaaauauaag accccggcgc cgccaccaug61 caccaccacc accaucaugu gucuaaggga gaggaacugu ucaccggcgu ggugccaauc121 cugguggaac uggacggaga ugugaauggc cacaaauuca gcgugcgggg cgagggcgag181 ggcgacgcua caaacggcaa gcuuacacug aaauucaucu guaccaccgg aaagcucccc241 gugcccuggc cuacacuggu caccacacug ggcuacggcg uggccugcuu cgccagauac301 cccgaccaca ugaaacaaca cgauuuuuuc aaguccgcca ugccugaggg cuaugugcag361 gagagaacca ucagcuucaa ggacgacggu acauacaaga ccagagccga ggugaaguuu421 gagggcgaca cccugguuaa uagaaucgug cugaagggca ucgacuucaa ggaagauggc481 aacauccugg gacacaagcu ggaauacaac uucaauagcc acaaggugua caucaccgcc541 gacaagcaga agaacggcau caaggccaac uucaaaaccc ggcacaacgu ggaagauggc601 ggaguccagc uggccgauca cuaccagcag aacaccccua ucggcgacgg cccugugcug661 cugccugaca accacuaccu gucucaccag agcaagcuga gcaaagaucc uaacgagaag721 cgggaccaca uggugcugaa ggaaagagug accgccgcug gcauuacaca cgacauggac781 gagcuguaca aguaagcugg agccucggug gccuagcuuc uugccccuug ggccuccccc841 cagccccucc uccccuuccu gcaccguacc cccgugucuu ugaauaaagu cugagugggc901 ggcaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa961 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaSEQ ID NO: 120, PRT, artificial, expression protein LC_E, coded by SEQ ID 114MHHHHHHPKINSFNYNDPVNDRTILYIKPGGCQEFYKSFNIMKNIWIIPERNVIGTTPQDFHPPTSLKNGDSSYYDPNYLQSDEEKDRFLKIVTKIFNRINNNLSGGILLEELSKANPYLGNDNTPDNQFHIGDASAVEIKFSNGSQDILLPNVIIMGAEPDLFETNSSNISLRNNYMPSNHRFGSIAIVTFSPEYSFRFNDNCMNEFIQDPALTLMHELIHSLHGLYGAKGITTKYTITQKQNPLITNIRGTNIEEFLTFGGTDLNIITSAQSND1YTNLEADYKK1ASKLSKVQVSNPLLNPYKDVFEAKYGLDKDASG1YSVN1NKFND1FKKLYSFTEFDLRTKFQVKCRQTYIGQYKYFKLSNLLNDSIYNISEGYNINNLKVNFRGQNANLNPRIITPITGRGLVKKIIRFCKNIVSVKGIR*SEQ ID NO: 121, PRT, artificial, expression protein LC C, coded by SEQ ID 115MHHHHHHPITINNFNYSDPVDNKNILYLDTHLNTLANEPEKAFRITGNIWVIPDRFSRNSNPNLNKPPRVTSPKSGYYDPNYLSTDSDKDTFLKEIIKLFKRINSREIGEELIYRLSTDIPFPGNNNTPINTFDFDVDFNSVDVKTRQGNNWVKTGSINPSVIITGPRENIIDPETSTFKLTNNTFAAQEGFGALSIISISPRFMLTYSNATNDVGEGRFSKSEFCMDPILILMHELNHAMHNLYGIAIPNDQTISSVTSNIFYSQYNVKLEYAEIYAFGGPTIDLIPKSARKYFEEKALDYYRSIAKRLNSITTANPSSFNKYIGEYKQKLIRKYRFVVESSGEVTVNRNKFVELYNELTQIFTEFNYAKIYNVQNRKIYLSNVYTPVTANILDDNVYDIQNGFNIPKSNLNVLFMGQNLSRNPALRKVNPENMLYLFTKFCHKAI*SEQ ID NO: 122, PRT, artificial, expression protein_LC_A2, coded by SEQ ID 116MHHHHHHPFVNKQFNYKDPVNGVDIAYIKIPNAGQMQPVKAFKIHNKIWVIPERDTFTNPEEGDLNPPPEAKQVPVSYYDSTYLSTDNEKDNYLKGVTKLFERIYSTDLGRMLLTSIVRGIPFWGGSTIDTELKVIDTNCINVIQPDGSYRSEELNLVIIGPSADIIQFECKSFGHDVLNLTRNGYGSTQYIRFSPDFTFGFEESLEVDTNPLLGAGKFATDPAVTLAHELIHAEHRLYGIAINPNRVFKVNTNAYYEMSGLEVSFEELRTFGGHDAKFIDSLQENEFRLYYYNKFKDVASTLNKAKSIIGTTASLQYMKNVFKEKYLLSEDTSGKFSVDKLKFDKLYKMLTEIYTEDNFVNFFKVINRKTYLNFDKAVFRINIVPDENYTIKDGFNLKGANLSTNFNGQNTEINSRNFTRLKNFTGLFEFYKLLCVRGIIPFK*SEQ ID NO: 123, PRT, artificial, expression protein LC Al Hall Neg, coded by SEQ ID 117MHHHHHHPFVNKQFNYKDPVNGVDIAYIKIPNAGQMQPVKAFKIHNKIWVIPERDTFTNPEEGDLNPPPEAKQVPVSYYDSTYLSTDNEKDNYLKGVTKLFERIYSTDLGRMLLTSIVRGIPFWGGSTIDTELKVIDTNCINVIQPDGSYRSEELNLVIIGPSADIIQFECKSFGHEVLNLTRNGYGSTQYIRFSPDFTFGFEESLEVDTNPLLGAGKFATDPAVTLAHQLIYAGHRLYGIAINPNRVFKVNTNAYYEMSGLEVSFEELRTFGGHDAKFIDSLQENEFRLYYYNKFKDIASTLNKAKSIVGTTASLQYMKNVFKEKYLLSEDTSGKFSVDKLKFDKLYKMLTE1YTEDNFVKFFKVLNRKTYENFDKAVFK1NIVPKVNYT1YDGFNLRNTNLAANFNGQNTEINNMNFTKLKNFTGLFEFYKLLCVRGIITSK*SEQ ID NO: 124, PRT, artificial, expression protein_LC_Al_Hall, coded by SEQ ID 118MHHHHHHPFVNKQFNYKDPVNGVDIAYIKIPNAGQMQPVKAFKIHNKIWVIPERDTFTNPEEGDLNPPPEAKQVPVSYYDSTYLSTDNEKDNYLKGVTKLFERIYSTDLGRMLLTSIVRGIPFWGGSTIDTELKVIDTNCINVIQPDGSYRSEELNLVIIGPSADIIQFECKSFGHEVLNLTRNGYGSTQYIRFSPDFTFGFEESLEVDTNPLLGAGKFATDPAVTLAHELIHAGHRLYGIAINPNRVFKVNTNAYYEMSGLEVSFEELRTFGGHDAKFIDSLQENEFRLYYYNKFKDIASTLNKAKSIVGTTASLQYMKNVFKEKYLLSEDTSGKFSVDKLKFDKLYKMLTEIYTEDNFVKFFKVLNRKTYLNFDKAVFKINIVPKVNYTIYDGFNLRNTNLAANFNGQNTEINNMNFTKLKNFTGLFEFYKLLCVRGIITSK*SEQ ID NO: 125, PRT, artificial, expression protein GreenLantem, coded by SEQ ID 119MHHHHHHVSKGEELFTGVVPILVELDGDVNGHKFSVRGEGEGDATNGKLTLKFICTTGKLPVPWPTLVTTLGYGVACFARYPDHMKQHDFFKSAMPEGYVQERTISFKDDGTYKTRAEVKFEGDTLVNRIVLKGIDFKEDGNILGHKLEYNFNSHKVYITADKQKNGIKANFKTRHNVEDGGVQLADHYQQNTPIGDGPVLLPDNHYLSHQSKLSKDPNEKRDHMVLKERVTAAGITHDMDELYK*SEQ ID NO: 126, DNA, artificial, Hall Strain Deactivated LC botulinumTCGAGCTCGGTACCTAATACGACTCACTATAAGGAGGAAATAAGAGAGAAAAGAAGAGTAAG AAGAAATATAAGAGCCACCATGCCCTTCGTCAATAAACAGTTTAACTATAAGGATCCTGTGAAT GGAGTGGACATCGCCTATATAAAAATACCGAACGCTGGACAAATGCAACCTGTGAAAGCTTTT AAGATACATAATAAGATTTGGGTGATCCCTGAGCGTGATACTTTCACAAATCCTGAGGAAGGC GATCTTAACCCTCCCCCGGAGGCTAAACAGGTTCCAGTGAGCTACTACGACTCCACCTATCTTTCCACCGACAACGAGAAGGACAACTATCTGAAGGGGGTGACTAAACTCTTCGAGAGAATTTA CTCAACCGATCTGGGCCGGATGTTACTGACCTCAATTGTCAGGGGAATCCCCTTTTGGGGAGG CTCTACTATCGATACAGAACTGAAAGTCATCGATACCAACTGCATTAACGTTATACAGCCCGAT GGCAGTTACCGAAGCGAGGAGCTCAACCTGGTTATTATCGGCCCAAGTGCTGATATCATCCAG TTCGAGTGTAAGTCGTTTGGGCACGAGGTGCTGAATCTGACACGGAATGGATATGGGAGCACGCAATACATCAGGTTTAGTCCCGATTTCACTTTCGGCTTCGAGGAGAGCCTTGAGGTGGACAC CAATCCATTGTTGGGGGCAGGCAAGTTCGCAACTGACCCAGCTGTTACCTTGGCGCACGCCCT GATTCACGCTGGCCATAGGCTGTACGGGATCGCCATCAACCCAAATCGGGTCTTCAAAGTTAA TACAAACGCCTACTACGAAATGAGCGGACTAGAAGTCTCTTTCGAAGCACTCCGAACATTTGG GGGTCATGACGCAAAGTTTATCGACTCCTTGCAGGAAAACGAGTTCCGCCTGTATTACTATAATAAGTTTAAGGACATCGCCTCAACACTCAATAAGGCCAAGTCAATTGTCGGTACGACAGCATCT CTACAGTATATGAAGAATGTATTTAAAGAAAAGTATCTTTTATCCGAAGACACTAGCGGCAAAT TCTCCGTAGACAAACTCAAGTTTGACAAGCTGTATAAGATGTTAACAGAAATTTACACAGAAG ACAACTTTGTGAAATTCTTTAAAGTGTTGAACAGAAAGACTTACCTGAACTTTGATAAGGCGG TGTTCAAGATCAACATTGTGCCCAAAGTCAACTACACGATATATGATGGATTTAATCTGCGCAATACCAACCTCGCCGCCAATTTCAATGGGCAGAACACCGAAATCAACAATATGAATTTCACCAA ACTGAAAAACTTCACTGGTCTCTTCGAGTTTTACAAGCTTCTGTGCGTAAGAGGTATTATTACC TCTAAATGAGCGGCCGCTTAATTAAGCTGCCTTCTGCGGGGCTTGCCTTCTGGCCATGCCCTTC TTCTCTCCCTTGCACCTGTACCTCTTGGTCTTTGAATAAAGCCTGAGTAGGAAGAAAAAAAA AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA AAAAAAAAAAAAAAAAAASEQ ID NO: 127, PRT, artificial, Hall Strain Deactivated LC botulinumMPFVNKQFNYKDPVNGVDIAYIKIPNAGQMQPVKAFKIHNKIWVIPERDTFTNPEEGDLNPPPEAKQVPVSYYDSTYLSTDNEKDNYLKGVTKLFERIYSTDLGRMLLTSIVRGIPFWG GSTIDTELKVIDTNCINVIQPDGSYRSEELNLVIIGPSADIIQFECKSFGHEVLNLTRNGYGS TQYIRFSPDFTFGFEESLEVDTNPLLGAGKFATDPAVTLAHALIHAGHRLYGIAINPNRVFK VNTNAYYEMSGLEVSFEALRTFGGHDAKFIDSLQENEFRLYYYNKFKDIASTLNKAKSIV GTTASLQYMKNVFKEKYLLSEDTSGKFSVDKLKFDKLYKMLTEIYTEDNFVKFFKVLNRKTYLNFDKAVFKINIVPKVNYTIYDGFNLRNTNLAANFNGQNTEINNMNFTKLKNFTGL FEF YKLLC VRGIIT SK

Claims

Claims 1. A method of cleaving a SNARE protein in a patient comprising administering to the patient a composition comprising an RNA molecule encoding the light chain of botulinum toxin to thereby cleave a SNARE protein.

2. The method of claim 1 wherein the pharmaceutically acceptable carrier comprises a lipid nanoparticle.

3. The method of claim 1 wherein the SNARE protein is SNAP-25 or syntaxin.

4. The method of claim 1 wherein the composition is administered by intra-muscular injection.

5. The method of claim 4 wherein the muscle is a facial muscle, or a head or neck muscle.

6. The method of claim 5 applied for the purpose of wrinkle reduction.

7. The method of claim 4 applied for the treatment of migraine headaches, urinary incontinence, or cervical dystonia.

8. The method of claim 1 wherein the composition is administered intra-dermally, optionally into the intra-dermal space.

9. The method of claim 8 wherein the composition is administered for the treatment of a condition selected from the group consisting of: excessive sweating, wound healing, rosacea, scarring, and skin wrinkle reduction.

10. The method of any one of claims 1-9 wherein the RNA molecule is administered in a lipid nanoparticle.

11. The method of any one of claims 1-9 wherein the RNA molecule is administered in a liposome or in a solid lipid nanoparticle.

12. The method of any one of claims 1-9 wherein the RNA molecule is administered as naked RNA. 4113. The method of any one of claims 1-10 wherein the RNA encodes a light chain of botulinum toxin having at least 90% sequence identity to a polypeptide sequence of any one of SEQ ID NO: 29-56.

14. The method of any one of claims 1-13 wherein the composition is administered by injection.

15. The method of any one of claims 1-14 wherein the composition is administered by needle-free injection.

16. The method of any one of claims 1-15 wherein the composition does not comprise an RNA molecule encoding a polypeptide sequence of the heavy chain of botulinum toxin, and further does not contain a polypeptide sequence of the heavy chain of botulinum toxin.

17. The method of any one of claims 1-16 wherein the composition is administered to a human patient.

18. A pharmaceutical composition comprising an RNA molecule encoding a light chain of botulinum toxin.

19. The pharmaceutical composition of claim 18 wherein the RNA molecule is comprised in a lipid nanoparticle.

20. The pharmaceutical composition of claim 18 wherein the RNA molecule encodes a polypeptide having at least 90% sequence identity to any one of SEQ ID NOs: 29-56.

21. The pharmaceutical composition of claim 20 for use in the treatment of a condition selected from the group consisting of: skin wrinkles, migraines, cervical dystonia, and urinary incontinence, wherein the composition is administered by intra-muscular injection.

22. The pharmaceutical composition of claim 20 for use in the treatment of a condition selected from the group consisting of: facial rejuvenation, hyperhidrosis, or for treating pain, rosacea, scarring, skin wrinkles, and for promoting wound healing, wherein the composition is administered by intra-dermal injection. 4223. The pharmaceutical composition of any one of claims 18-22 wherein the composition does not comprise RNA encoding for the heavy chain of botulinum toxin.

24. The pharmaceutical composition of any one of claims 18-23 wherein the lipid nanoparticle comprises SM-102, polyethylene glycol [PEG] 2000 dimyristoyl glycerol (DMG), cholesterol, and 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC).

25. The pharmaceutical composition of claim 24 wherein the lipid nanoparticle further comprises stabilizers selected from the group consisting of: tromethamine, tromethamine hydrochloride, acetic acid, sodium acetate, and sucrose.

26. The pharmaceutical composition of any one of claims 18-23 wherein the lipid nanoparticle comprises (4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2hexyldecanoate), 2 [(polyethylene glycol)-2000]-N,N-ditetradecylacetamide, 1,2-distearoyl-sn-glycero-3- phosphocholine, and cholesterol), tromethamine, and tromethamine hydrochloride.

27. The pharmaceutical composition of any one of claims 18-26 wherein the lipid nanoparticle has an average diameter between 86-104 nm.

28. The pharmaceutical composition of any one of claims 18-26 wherein the RNA comprises a sequence having at least 90% sequence identity to any one of SEQ ID NOs: 85-112.

29. The pharmaceutical composition of any one of claims 18-26 where the RNA comprises a sequence having at least 90% sequence identity to any one of SEQ ID NO: 114-117.

30. A method of synthesizing a toxic polypeptide comprising a light chain and a heavy chain, the method comprising: synthesizing the light chain of the toxic polypeptide in a first laboratory facility that does not meet the requirements of a government prescribed biosafety level for the toxic polypeptide; synthesizing the heavy chain of the toxic polypeptide in a second laboratory facility that does not meet the requirements of the government prescribed biosafety level for the toxic polypeptide; 43bringing the synthesized light chain and heavy chain together in a laboratory that meets the requirements of the government prescribed biosafety level for the toxic polypeptide, to thereby synthesize the toxic polypeptide.

31. The method of claim 30 wherein bringing the light chain and heavy chain together comprises creating a disulfide bond between the heavy chain and the light chain.

32. The method of any one of claims 30-31 wherein the light chain comprises a polypeptide of any one of SEQ ID NOs: 29-56, and the heavy chain comprises a polypeptide of any one of SEQ ID NOs: 57-84.

33. The method of claim 30-32 wherein the toxic polypeptide is botulinum toxin and the government prescribed biosafety level is biosafety level 2.

34. The method of claim 30-32 wherein the toxic polypeptide is botulinum toxin and the government prescribed biosafety level is biosafety level 3.

35. The method of claim 30-34 wherein the heavy chain and the light chain are produced in separate strains and / or from separate open reading frames.

36. The method of claim 30-35 wherein the toxic polypeptide is selected from the group consisting of: botulinum toxin (BoNT), scorpion toxin, snake toxin, and leech toxin.

37. The method of claim 36 wherein the toxin polypeptide is botulinum toxin (BoNT).

38. The method of claim 37 wherein the botulinum toxin is sub-type A. 44

Images