Modified kozak sequences for production of recombinant aav
Patent Information
- Application Number
- EP2024887034
- Authority / Receiving Office
- EP · EP
- Patent Type
- Applications
- Current Assignee / Owner
- Priority Date
- 2023-11-03
- Filing Date
- 2024-11-01
- Publication Date
- 2026-09-09
AI Technical Summary
The efficiency of recombinant adeno-associated virus (rAAV) production in insect cells, particularly for serotype AAV5, is lower compared to other cell types or serotypes, due to altered stoichiometry of capsid proteins.
The use of modified Kozak sequences and translational enhancer sequences in nucleic acid molecules encoding AAV Cap and Rep proteins, which are integrated into AAV Rep-Cap plasmids, to improve the translation efficiency and stoichiometry of capsid proteins in insect cells.
This approach enhances the production efficiency of rAAV, particularly for AAV5, by achieving a desired ratio of expressed Cap proteins (1:1:10 VP1:VP2:VP3) and improving overall virus yield and infectivity.
Smart Images

Figure US2024054232_08052025_PF_FP_ABST
Abstract
Description
MODIFIED KOZAK SEQUENCES FOR PRODUCTION OF RECOMBINANT AAVBACKGROUND
[0001] Adeno-associated virus (AAV) technology has quickly become a dominant form of gene therapy for genetic diseases. Recombinant adeno-associated viruses (rAAVs) can be produced in large scale in a variety of host cell systems, including insect cells, such as Sf9 cells.SUMMARY
[0002] The present disclosure recognizes that challenges associated with rAAV production in insect cells remain. Efficiency of production of rAAV in insect cells can depend upon the AAV serotype being produced. For example, serotype AAV5 production in insect cells can be less efficient than other cell types (e.g., human cells) or other AAV serotypes, at least due in part to altered stoichiometry of capsid proteins.
[0003] The present disclosure encompasses, among other things, nucleic acids useful in the production of rAAV. In some embodiments, the present disclosure provides AAV Rep-Cap plasmids useful in the production of rAAV. In some embodiments, the present disclosure provides Cap sequences useful in the production of rAAV. Alternatively or additionally, in some embodiments, the present disclosure provides Rep sequences useful in the production of rAAV In some embodiments, the present disclosure provides modified Kozak sequences useful in the production of rAAV. In some embodiments, the present disclosure provides a nucleic acid molecule encoding AAV Cap wherein the nucleic acid molecule comprises a 5’ UTR and a modified Kozak sequence useful in the production of rAAV. Alternatively or additionally, in some embodiments, the present disclosure provides a nucleic acid molecule encoding AAV Rep wherein the nucleic acid molecule comprises a 5’ UTR and a modified Kozak sequence useful in the production of rAAV.
[0004] In some embodiments, the present disclosure provides translational enhancer sequence(s) useful in the production of rAAV. In some embodiments, the present disclosure provides a nucleic acid molecule encoding AAV Cap wherein the nucleic acid moleculecomprises a 5’ UTR and a translational enhancer sequence. In some embodiments, the present disclosure provides a nucleic acid molecule encoding AAV Rep wherein the nucleic acid molecule comprises a 5 ’ UTR and a translational enhancer sequence.
[0005] In some embodiments, the present disclosure provides a nucleic acid molecule encoding an adeno- associated virus (AAV) Cap, wherein the nucleic acid molecule comprises a 5’ UTR and a modified Kozak sequence selected from SEQ ID NOs: 2-21. In some embodiments, the modified Kozak sequence is attenuated. In some embodiments, the attenuated Kozak sequence has a translation efficiency less than a wild type, or canonical Kozak sequence. In some embodiments, the nucleic acid molecule further comprises a translational enhancer sequence. In some embodiments, the translational enhancer sequence is selected from: Syn21 (SEQ ID NO: 25), L21 (SEQ ID NO: 26), AcNPV (SEQ ID NO: 27), EoNPV (SEQ ID NO: 28), TMV (SEQ ID NO: 29).
[0006] In some embodiments, the present disclosure provides a nucleic acid molecule encoding an adeno- associated virus (AAV) Rep, wherein the nucleic acid molecule comprises a modified Kozak sequence selected from SEQ ID NOs: 2-21. In some embodiments, the present disclosure provides a nucleic acid molecule encoding an adeno- associated virus (AAV) Rep, wherein the nucleic acid molecule is or comprises modified Kozak sequence SEQ ID NO:8. In some embodiments, the modified Kozak sequence is attenuated. In some embodiments, the attenuated Kozak sequence has a translation efficiency less than a wild type, or canonical Kozak sequence. In some embodiments, the nucleic acid molecule further comprises a translational enhancer sequence. In some embodiments, the translational enhancer sequence is selected from: Syn21 (SEQ ID NO: 25), L21 (SEQ ID NO: 26), AcNPV (SEQ ID NO: 27), EoNPV (SEQ ID NO: 28), TMV (SEQ ID NO: 29).
[0007] In some embodiments, the present disclosure provides a nucleic acid molecule encoding a first nucleic acid sequence encoding AAV Cap wherein the first nucleic acid sequence comprises a 5’ UTR, and a modified Kozak sequence selected from SEQ ID NOs: 2-21; and a second nucleic acid sequence encoding AAV Rep wherein the first nucleic acid sequence comprises a 5 ’ UTR; and a modified Kozak sequence selected from SEQ ID NOs: 2-21. In some embodiments, the first and / or second nucleic acid sequences further comprise a translational enhancer sequence selected from: Syn21 (SEQ ID NO: 25), L21(SEQ ID NO: 26), AcNPV (SEQ ID NO: 27), EoNPV (SEQ ID NO: 28), TMV (SEQ ID NO: 29).
[0008] In some embodiments, the present disclosure provides a method of producing recombinant AAV (rAAV) particles comprising a nucleic acid molecule(s) described herein (e.g., a nucleic acid encoding AAV Rep and / or a nucleic acid encoding AAV Cap) in a producer cell. In some embodiments, a method of producing rAAV comprises transfecting a nucleic acid molecule(s) described herein into a producer cell. In some embodiments, the producer cell is an insect cell. In some embodiments, the producer cell is Sf9 or a derivative cell line thereof. In some embodiments, the rAAV capsid is derived from AAV serotype 5 (AAV5). In some embodiments, the rAAV Rep is derived from AAV serotype 2 (AAV2).
[0009] In some embodiments, the present disclosure provides a nucleic acid molecule encoding adeno-associated virus (AAV) Cap, wherein the nucleic acid molecule comprises a 5’UTR and a translational enhancer sequence selected from SEQ ID NOs: 25- 29. In some embodiments, the nucleic acid molecule encoding AAV Cap further comprises a modified Kozak sequence selected from SEQ ID NOs: 2-21.
[0010] In some embodiments, the present disclosure provides a nucleic acid molecule encoding adeno-associated virus (AAV) Rep, wherein the nucleic acid molecule comprises a 5’UTR and a translational enhancer sequence selected from SEQ ID NOs: 25- 27. In some embodiments, the nucleic acid molecule encoding AAV Rep further comprises a modified Kozak sequence that is or comprises SEQ ID NO: 8.
[0011] These, and other aspects encompassed by the present disclosure, are described in more detail below and in the claims.BRIEF DESCRIPTION OF THE DRAWINGS
[0012] Figure 1 shows exemplary mechanisms of regulation of AAV VP protein ratio production.
[0013] Figure 2 shows two exemplary expression cassette solutions for regulation of AAV VP protein ratio production.
[0014] Figure 3 shows exemplary selection criteria for attenuated Kozak sequences.
[0015] Figure 4 shows exemplary attenuated Kozak sequences.
[0016] Figure 5 schematically shows VP protein expression cassette with and without a translational enhancer.
[0017] Figures 6A-6B show exemplary Jess Simple Western analysis of VP protein expression in Sf9 cells from plasmids comprising an attenuated Kozak sequence.
[0018] Figure 7 shows exemplary protein expression data of VP proteins from expression plasmids comprising indicated attenuated Kozak sequence.
[0019] Figures 8A-8B show exemplary Jess Simple Western analysis of VP protein expression in Sf9 cells from plasmids comprising a translational enhancer sequence and an attenuated Kozak sequence.
[0020] Figures 9A-9C show exemplary protein capillary electrophoresis analysis performed on purified AAV virus samples obtained using pFBacX-AAVRep2ACap5_40AE AcNPV construct (SEQ ID NO: 34).
[0021] Figures 10A-10B shows exemplary protein capillary electrophoresis analysis performed on purified AAV virus samples obtained using pFBacX-AAVRep2ACap5_40AE L21 construct (SEQ ID NO: 37).
[0022] Figures 11A-11C shows exemplary protein capillary electrophoresis analysis performed on purified AAV virus samples obtained using pFBacX-AAVRep2ACap5_40AE Syn21 construct (SEQ ID NO: 38).
[0023] Figure 12 shows exemplary yield data of AAV5 -virus produced by SF9 cells using pFBacX-AAVRep2ACap5_40AE AcNPV (SEQ ID NO: 34), pFBacX- AAVRep2ACap5_40AE L21 (SEQ ID NO: 37), and pFBacX-AAVRep2ACap5_40AE Syn21 constructs (SEQ ID NO: 38).
[0024] Figure 13 shows exemplary infectivity comparison of AAV5 virus isolated from SF9 and HEK293 cells wherein P:I value equals to viral particle number necessary to infect one cell at chosen experimental conditions.
[0025] Figure 14 shows exemplary attenuated Kozak Rep translation initiation sequence maps.
[0026] Figure 15 shows exemplary JESS Simple Western analysis of Rep protein expression in Sf9 cells from indicated plasmids comprising a translational enhancer sequence and an attenuated Kozak sequence.
[0027] Figure 16 shows exemplary rAAV yield data of AAV5 -virus produced by SF9 cells using, pFBacX-AAVRep2ACap5_40AE L21 (SEQ ID NO: 37), pB-40A-Rep2Cap5 (SEQ ID NO: 46), pB-40L-Rep2Cap5 (SEQ ID NO: 47), pB-40A-Rep2Cap5 (SEQ ID NO: 48)
[0028] Figure 17 shows a plasmid map of pB-40A-Rep2Cap5.
[0029] Figure 18 shows a plasmid map of pB-40L-Rep2Cap5.
[0030] Figure 19 shows a plasmid map of pB-40S-Rep2Cap5.DEFINITIONS
[0031] Agent-. In general, the term “agent”, as used herein, is used to refer to an entity (e.g., for example, a lipid, metal, nucleic acid, polypeptide, polysaccharide, small molecule, etc, or complex, combination, mixture or system [e.g., cell, tissue, organism] thereof), or phenomenon (e.g., heat, electric current or field, magnetic force or field, etc). In appropriate circumstances, as will be clear from context to those skilled in the art, the term may be utilized to refer to an entity that is or comprises a cell or organism, or a fraction, extract, or component thereof. Alternatively or additionally, as context will make clear, the term may be used to refer to a natural product in that it is found in and / or is obtained from nature. In some instances, again as will be clear from context, the term may be used to refer to one or more entities that is man-made in that it is designed, engineered, and / or produced through action of the hand of man and / or is not found in nature. In some embodiments, an agent may be utilized in isolated or pure form; in some embodiments, an agent may be utilized in crude form. In some embodiments, potential agents may be provided as collections or libraries, for example that may be screened to identify or characterize activeagents within them. In some cases, the term “agent” may refer to a compound or entity that is or comprises a polymer; in some cases, the term may refer to a compound or entity that comprises one or more polymeric moieties. In some embodiments, the term “agent” may refer to a compound or entity that is not a polymer and / or is substantially free of any polymer and / or of one or more particular polymeric moieties. In some embodiments, the term may refer to a compound or entity that lacks or is substantially free of any polymeric moiety.
[0032] Approximately / about-. As used herein, the term “approximately” or “about,” as applied to one or more values of interest, refers to a value that is similar to a stated reference value. In certain embodiments, the term “approximately” or “about” refers to a range of values that fall within 25%, 20%, 19%, 18%, 17%, 16%, 15%, 14%, 13%, 12%, 11%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, or less in either direction (greater than or less than) of the stated reference value unless otherwise stated or otherwise evident from the context (except where such number would exceed 100% of a possible value).
[0033] Attenuated: As used herein, the term “attenuated” refers to a component, value, activity, or parameter that is lessened or weakened. In certain embodiments, the term “attenuated” refers to a range of values that fall within 55%, 50%, 45%, 44%, 42%, 41%, 40%, 39%, 38%, 37%, 36, 35%, 30%, 25% or less than the stated reference value. For example, in some embodiments, an attenuated Kozak sequence refers to a modified Kozak sequence wherein a translational efficiency range value falls within 45%, 44%, 42%, 41%, 40%, 39%, 38%, 37%, 36, 35% or less than the stated reference value of an unmodified Kozak sequence.
[0034] Comparable: As used herein, the term “comparable” refers to two or more agents, entities, situations, sets of conditions, etc., that may not be identical to one another but that are sufficiently similar to permit comparison therebetween so that one skilled in the art will appreciate that conclusions may reasonably be drawn based on differences or similarities observed. In some embodiments, comparable sets of conditions, circumstances, individuals, or populations are characterized by a plurality of substantially identical features and one or a small number of varied features. Those of ordinary skill in the art will understand, in context, what degree of identity is required in any given circumstance for two or more such agents, entities, situations, sets of conditions, etc to be considered comparable.For example, those of ordinary skill in the art will appreciate that sets of circumstances, individuals, or populations are comparable to one another when characterized by a sufficient number and type of substantially identical features to warrant a reasonable conclusion that differences in results obtained or phenomena observed under or with different sets of circumstances, individuals, or populations are caused by or indicative of the variation in those features that are varied.
[0035] Corresponding to: As used herein, the term “corresponding to” may be used to designate the position / identity of a structural element in a compound or composition through comparison with an appropriate reference compound or composition. For example, in some embodiments, a monomeric residue in a polymer (e.g., an amino acid residue in a polypeptide or a nucleic acid residue in a polynucleotide) may be identified as “corresponding to” a residue in an appropriate reference polymer. For example, those of ordinary skill will appreciate that, for purposes of simplicity, residues in a polypeptide are often designated using a canonical numbering system based on a reference related polypeptide, so that an amino acid “corresponding to” a residue at position 190, for example, need not actually be the 190thamino acid in a particular amino acid chain but rather corresponds to the residue found at 190 in the reference polypeptide; those of ordinary skill in the art readily appreciate how to identify “corresponding” amino acids. For example, those skilled in the art will be aware of various sequence alignment strategies, including software programs such as, for example, BLAST, CS-BLAST, CUSASW++, DIAMOND, FASTA, GGSEARCH / GLSEARCH, Genoogle, HMMER, HHpred / Hhsearch, IDF, Infernal, KLAST, USEARCH, parasail, PSI-BLAST, PSI-Search, ScalaBLAST, Sequilab, SAM, SSEARCH, SWAPHI, SWAPHI-LS, SWIMM, or SWIPE that can be utilized, for example, to identify “corresponding” residues in polypeptides and / or nucleic acids in accordance with the present disclosure.
[0036] Downstream : As used herein, the term “downstream” refers to the location or position of a nucleic acid sequence relative to a reference nucleic acid sequence, particularly a position that, during RNA transcription, is closer to the 3’ end of the transcribed RNA molecule encoded by the reference sequence. For example, for two sequences, A and B, such that sequence A is downstream of sequence B, transcription of sequence B proceeds toward sequence A.
[0037] Nucleic acid As used herein, in its broadest sense, the term “nucleic acid” refers to any compound and / or substance that is or can be incorporated into an oligonucleotide chain. In some embodiments, a nucleic acid is a compound and / or substance that is or can be incorporated into an oligonucleotide chain via a phosphodiester linkage. As will be clear from context, in some embodiments, “nucleic acid" refers to an individual nucleic acid residue (e.g., a nucleotide and / or nucleoside); in some embodiments, “nucleic acid" refers to an oligonucleotide chain comprising individual nucleic acid residues. In some embodiments, a “nucleic acid’' is or comprises RNA; in some embodiments, a “nucleic acid” is or comprises DNA. In some embodiments, a nucleic acid is, comprises, or consists of one or more natural nucleic acid residues. In some embodiments, a nucleic acid is, comprises, or consists of one or more nucleic acid analogs. In some embodiments, a nucleic acid analog differs from a nucleic acid in that it does not utilize a phosphodiester backbone. For example, in some embodiments, a nucleic acid is, comprises, or consists of one or more “peptide nucleic acids”, which are known in the art and have peptide bonds instead of phosphodiester bonds in the backbone, are considered within the scope of the present invention. Alternatively or additionally, in some embodiments, a nucleic acid has one or more phosphorothioate and / or 5’-N- phosphoramidite linkages rather than phosphodiester bonds. In some embodiments, a nucleic acid is, comprises, or consists of one or more natural nucleosides (e.g., adenosine, thymidine, guanosine, cytidine, uridine, deoxyadenosine, deoxythymidine, deoxy guanosine, and deoxy cytidine). In some embodiments, a nucleic acid is, comprises, or consists of one or more nucleoside analogs (e.g., 2-aminoadenosine, 2-thiothymidine, inosine, pyrrolo- pyrimidine, 3 -methyl adenosine, 5 -methylcytidine, C-5 propynyl-cytidine, C-5 propynyl- uridine, 2-aminoadenosine, C5 -bromouridine, C5-fluorouridine, C5 -iodouridine, C5- propynyl-uridine, C5 -propynyl-cytidine, C5-methylcytidine, 2-aminoadenosine, 7- deazaadenosine, 7-deazaguanosine, 8-oxoadenosine, 8-oxoguanosine, 0(6)-methylguanine, 2-thiocytidine, methylated bases, intercalated bases, and combinations thereof). In some embodiments, a nucleic acid comprises one or more modified sugars (e.g., 2’ -fluororibose, ribose, 2’ -deoxyribose, arabinose, and hexose) as compared with those in natural nucleic acids. In some embodiments, a nucleic acid has a nucleotide sequence that encodes a functional gene product such as an RNA or protein. In some embodiments, a nucleic acid includes one or more introns. In some embodiments, nucleic acids are prepared by one or more of isolation from a natural source, enzymatic synthesis by polymerization based on acomplementary template (zn vivo or in vitro), reproduction in a recombinant cell or system, and chemical synthesis. In some embodiments, a nucleic acid is at least 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 1 10, 120, 130, 140, 150, 160, 170, 180, 190, 20, 225, 250, 275, 300, 325, 350, 375, 400, 425, 450, 475, 500, 600, 700, 800, 900, 1000, 1500, 2000, 2500, 3000, 3500, 4000, 4500, 5000 or more residues long. In some embodiments, a nucleic acid is partly or wholly single stranded; in some embodiments, a nucleic acid is partly or wholly double stranded. In some embodiments a nucleic acid has a nucleotide sequence comprising at least one element that encodes, or is the complement of a sequence that encodes, a polypeptide. In some embodiments, a nucleic acid has enzymatic activity.
[0038] Operably linked'. As used herein, the term “operably linked” refers to a juxtaposition wherein the components described are in a relationship permitting them to function in their intended manner. A control element “operably linked” to a functional element is associated in such a way that expression and / or activity of the functional element is achieved under conditions compatible with the control element. In some embodiments, “operably linked” control elements are contiguous (e.g., covalently linked) with the coding elements of interest; in some embodiments, control elements act in trans to or otherwise at a distance from the functional element of interest.
[0039] Producer cell: As used herein, the term “producer cell” refers to any cell used to produce recombinant AAV (rAAV). In some embodiments, a producer cell is a mammalian cell. In some embodiments, a producer cell is a transformed mammalian cell. In some embodiments, a producer cell is a Vero, HeLa, HEK293, HEK293T cell or derivative thereof. In some embodiments, a producer cell is an insect cell. In some embodiments, a producer cell is a transformed insect cell. In some embodiments, a producer cell is an Sf9 cell or derivative thereof.
[0040] Transformation: As used herein, the term “transformation” refers to any process by which exogenous DNA is introduced into a host cell. Transformation may occur under natural or artificial conditions using various methods well known in the art. Transformation may rely on any known method for the insertion of foreign nucleic acid sequences into a prokaryotic or eukaryotic host cell. In some embodiments, a particular transformation methodology is selected based on the host cell being transformed and mayinclude, but is not limited to, viral infection, electroporation, mating, lipofection. In some embodiments, a “transformed” cell is stably transformed in that the inserted DNA is capable of replication either as an autonomously replicating plasmid or as part of the host chromosome. In some embodiments, a transformed cell transiently expresses introduced nucleic acid for limited periods of time.
[0041] Upstream: As used herein, the term “upstream” refers to the location or position of a nucleic acid sequence relative to a reference nucleic acid sequence, particularly a position that, during RNA transcription, is closer to the 5’ end of the transcribed RNA molecule encoded by the reference sequence. For example, for two sequences, A and B, such that sequence A is upstream of sequence B, transcription of sequence B proceeds away from sequence A.
[0042] Vector-. As used herein, the term “vector” refers to a nucleic acid molecule capable of transporting another nucleic acid to which it has been linked. One type of vector is a “plasmid”, which refers to a circular double stranded DNA loop into which additional DNA segments may be ligated. Another type of vector is a viral vector, wherein additional DNA segments may be ligated into the viral genome. Certain vectors are capable of autonomous replication in a host cell into which they are introduced (e.g., bacterial vectors having a bacterial origin of replication and episomal mammalian vectors). Other vectors (e.g., non-episomal mammalian vectors) can be integrated into the genome of a host cell upon introduction into the host cell, and thereby are replicated along with the host genome. Moreover, certain vectors are capable of directing the expression of genes to which they are operatively linked. Such vectors are referred to herein as “expression vectors.” Standard techniques may be used for recombinant DNA, oligonucleotide synthesis, and tissue culture and transformation (e.g., electroporation, lipofection). Enzymatic reactions and purification techniques may be performed according to manufacturer’s specifications or as commonly accomplished in the art or as described herein. The foregoing techniques and procedures may be generally performed according to conventional methods well known in the art and as described in various general and more specific references that are cited and discussed throughout the present specification. See e.g., Sambrook et al., Molecular Cloning: A Laboratory Manual (2d ed., Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y. (1989)), which is incorporated herein by reference for any purpose.
[0043] Wild-type: As used herein, the term “wild-type” has its art-understood meaning that refers to an entity having a structure and / or activity as found in nature in a “normal” (as contrasted with mutant, diseased, altered, etc.) state or context. Those of ordinary skill in the art will appreciate that wild-type genes and polypeptides often exist in multiple different forms (e.g., alleles).DETAILED DESCRIPTION OF CERTAIN EMBODIMENTS
[0044] One major ongoing challenge in the development and optimization of rAAV vectors for clinical applications is to maximize the amount of virus produced per production run. Due to their non-proliferative nature, rAAV production depends, in part, on the transfection efficiency of parvoviral genomic components into producer cell lines (for example human embryonic kidney cells, HEK293 or HEK293T, or insect cells e.g., Sf9) and properly regulated production of proteins encoded by those components. Thus, it remains of high importance to develop means to increase rAAV production.
[0045] Among other things, the present disclosure provides compositions and methods for production of AAV (e.g., recombinant AAV (rAAV)). In some embodiments, the present disclosure provides compositions and methods for production of AAV Cap proteins (e.g., VP1, VP2, and / or VP3). In some embodiments, the present disclosure provides compositions and methods for production of AAV Rep proteins (e.g., Rep78 and Rep52). In some embodiments, the present disclosure provides compositions and methods for the production of AAV Rep and Cap proteins.
[0046] In some embodiments, the present disclosure provides compositions and methods for production of rAAV of a specific AAV serotype (e.g., AAV5 serotype). Alternatively or additionally, in some embodiments, the present disclosure describes compositions and methods for the production of AAV Rep proteins (e.g., Rep78 and Rep52). In some embodiments, the present disclosure provides compositions and methods for production of rAAV comprising Rep proteins from a specific AAV serotype (e.g., AAV2 serotype).
[0047] Without wishing to be bound by any particular theory, the ratio of AAV capsid expression affects capsid physical features, titer, and infectivity. Among other things,the present disclosure recognizes that modification of the sequences regulating translation of Cap proteins (e.g., VP1, VP2, and VP3) can improve production of rAAV. In some embodiments, a ratio of expressed Cap protein of 1: 1:10 VP1:VP2:VP3 is a desired or theoretical value. In some embodiments, the present disclosure provides modifications of the sequences regulating translation of Cap proteins (e.g., VP1, VP2, and VP3) to approach or achieve a ratio of expressed Cap protein of 1: 1: 10 VP1:VP2:VP3.
[0048] Among other things, the present disclosure recognizes that modification of the sequences regulating translation of Rep proteins (e.g., Rep78 and Rep52) can improve production of rAAV.
[0049] In some embodiments, the present disclosure provides methods or compositions useful for the regulation of AAV Cap and / or Rep protein translation. In some embodiments, the present disclosure relates to regulation of AAV capsid protein expression (e.g., regulation of ratio of VP1:VP2:VP3 expression). Alternatively or additionally, the present disclosure relates to regulation of AAV Rep protein expression (e.g., regulation of Rep78 and Rep52 expression).
[0050] Some studies have suggested that Kozak sequence attenuation might result in AAV capsid expression closer to a ratio of 1:1:10 VP1:VP2:VP3 and improved rAAV production in insect cells (e.g., Sf9 cells). See, e.g., Kondratov et al., 2017, Molecular Therapy, 25(12), pp.2661-2675.
[0051] The present disclosure goes beyond prior studies and addresses the abovedescribed technical challenges in rAAV production by providing compositions and methods comprising, among other things, modified Kozak sequences not previously described or tested.
[0052] Some studies also suggest that sequence elements derived from plant and insect viruses increase apparent translational efficiency of RNA in Drosophila. See, e.g., Pfeiffer BD et al., Proc Natl Acad Sci U S A. 2012 Apr 24; 109(17): 6626-31. The present disclosure addresses the above-described technical challenges in rAAV production by providing compositions and methods comprising, among other things, a 5’ UTR and a translational enhancer sequence in nucleotide sequences encoding AAV Cap.AAV Rep-Cap Plasmids
[0053] Among other things, the present disclosure provides AAV Rep-Cap plasmids useful for production of AAV (e.g., rAAV). In some embodiments, an AAV Rep-Cap plasmid comprises AAV Rep and Cap genes. In some embodiments, an AAV Rep-Cap plasmid comprises AAV Rep genes derived from a particular serotype. In some embodiments, an AAV Rep sequence comprises AAV genes derived from AAV2. In some embodiments, an AAV Rep-Cap plasmid comprises modified AAV2 Rep genes (e.g., modified to comprise one or more nucleic acid substitutions, deletions, or additions). In some embodiments, an AAV Rep-Cap plasmid comprises AAV Cap genes derived from a particular AAV serotype. In some embodiments, an AAV Cap sequence comprises AAV genes derived from AAV5. In some embodiments, an AAV Rep-Cap plasmid comprises modified AAV5 Cap genes (e.g., modified to comprise one or more nucleic acid substitutions, deletions, or additions).
[0054] In some embodiments, an AAV Rep-Cap plasmid comprises an AAV Rep- Cap sequence. In some embodiments, a producer cell comprises an AAV Rep-Cap sequence. In some embodiments, a producer cell line permanently or transiently expresses an AAV Rep-Cap sequence. In some embodiments, a producer cell line comprises an AAV Rep-Cap plasmid.
[0055] In some embodiments, an AAV Rep-Cap plasmid comprises VP1, VP2, and VP3 genes. In some embodiments, an AAV Rep-Cap plasmid comprises one or more promoters. In some embodiments, an AAV Rep-Cap plasmid comprises one or more promoters operably linked to downstream gene(s). In some embodiments, an AAV Rep-Cap plasmid comprises a promoter upstream (i.e., 5’ of) of a VP1 gene, a promoter upstream of a VP2 gene, and / or a promoter upstream of a VP3 gene. In some embodiments, an AAV Rep- Cap plasmid comprises one or more separate expression cassettes for VP protein expression. In some embodiments, an AAV Rep-Cap plasmid comprises two separate expression cassettes for VP protein expression. In some embodiments, an AAV Rep-Cap plasmid comprises two overlapping expression cassettes for VP protein expression.
[0056] In some embodiments, an AAV Rep-Cap plasmid comprises a Rep78 gene and a Rep52 gene. In some embodiments, an AAV Rep-Cap plasmid comprises a Rep78encoding sequence and a Rep52 encoding sequence. In some embodiments, an AAV Rep- Cap plasmid comprises a promoter upstream (i.e., 5’ of) of a Rep78 encoding sequence and a Rep52 encoding sequence.Atenuated Kozak Sequences
[0057] One of skill in the art will understand various structures and events associated with translation of eukaryotic RNA. One of skill in the art will understand a Kozak sequence refers to a sequence of nucleotides that functions as a translation initiation site.
[0058] In some embodiments, the present disclosure relates to modified Kozak sequences. In some embodiments, a modified Kozak sequence is a Kozak sequence that comprises a nucleotide sequence other than a wild type or canonical Kozak sequence. In some embodiments, the present disclosure relates to attenuated Kozak sequences. In some embodiments, a modified Kozak sequence is attenuated. In some embodiments, an attenuated sequence has a translation efficiency different than a wild type or canonical Kozak sequence. In some embodiments, an attenuated sequence has a translation efficiency less than a wild type or canonical Kozak sequence. One of skill in the art will appreciate that Kozak sequences can also be referred to as translation initiation sequences (TIS). In some embodiments, the present disclosure describes methods for the screening and selection of attenuated Kozak sequences that may be particularly useful in the production of AAV. In some embodiments, the present disclosure provides compositions comprising a 5’ UTR and attenuated Kozak sequences that may be particularly useful in the production of AAV.
[0059] Among other things, the present disclosure provides modified (e.g., attenuated) Kozak sequences that are particularly useful for production of rAAV (e.g., AAV5). In some embodiments, an AAV Cap sequence comprises a modified Kozak sequence as described herein. In some embodiments, attenuated Kozak sequences described herein are associated with the translation initiation codon (e.g., ATG / AUG) for VP1. In some embodiments, a modified Kozak sequence described herein comprises a translation initiation codon (e.g., ATG / AUG) for VP1. In some embodiments, the translation initiation codons and associated Kozak sequences for VP2 and VP3 are not modified (e.g., are wildtype sequences).
[0060] In some embodiments, an AAV Rep sequence comprises a modified Kozak sequence as described herein. In some embodiments, attenuated Kozak sequences described herein are associated with the translation initiation codon (e.g., ATG / AUG) for Rep78.
[0061] In some embodiments, a modified Kozak sequence is modified in the six nucleotides upstream of a translation initiation codon (e.g., ATG / AUG). In some embodiments, a modified Kozak sequence is modified relative to a native Kozak sequence (e.g., a wild-type sequence). In some embodiments, a modified Kozak sequence is modified relative to a control Kozak sequence. In some embodiments, a control Kozak sequence is UGUUUUAUGUC (SEQ ID NO: 1). In some embodiments, an attenuated Kozak sequence has one or more nucleotide substitutions relative to a control Kozak sequence (e.g., 1, 2, 3, 4, 5, 6, or more substitutions). In some embodiments, a modified Kozak sequence has one or more nucleotide substitutions relative to a control Kozak sequence (e.g., 1, 2, 3, 4, 5, 6, or more substitutions) in the six nucleotides upstream of a translation initiation codon (e.g., ATG / AUG).
[0062] In some embodiments, an attenuated Kozak sequence is selected from a library of possible variants. In some embodiments, the criteria for selection of an attenuated Kozak sequence comprises fitting possible variants to a consensus sequence. In some embodiments, a consensus sequence for selection is NNNNNNAUGNN (SEQ ID NO: 22), RNXUXUAUGNY (SEQ ID NO: 23), and / or RNXUXUAUGUC (SEQ ID NO: 24); wherein "‘R” denotes U or C; ”N" denotes A, G, C, or U; “X” denotes U or G; “Y” denotes A, C, or U; and “Z” denotes G or C.
[0063] In some embodiments, Kozak sequences are associated with a theoretical translation efficiency. In some embodiments, selection criteria for attenuated Kozak sequences comprise selecting sequences with a theoretical translation efficiency within a particular range. In some embodiments, a particular range of theoretical efficiencies for selection is 25% to 55%. In some embodiments, a particular range of theoretical efficiencies for selection is 30% to 50%. In some embodiments, a particular range of theoretical efficiencies for selection is 35% to 45%. In some embodiments, a particular range of theoretical efficiencies for selection is intermediate values between any of the foregoing values.Translational Enhancer Sequences
[0064] Among other things, the present disclosure provides translational enhancer sequences that improve production of AAV (e.g., AAV5). In some embodiments, the present disclosure describes methods for the screening and selection of translational enhancer sequences useful in the production of AAV. In some embodiments, the present disclosure describes compositions comprising translational enhancer sequences as described herein. In some embodiments, the present disclosure describes compositions comprising a 5’ UTR and translational enhancer sequences as described herein.
[0065] In some embodiments, a AAV Cap sequence comprises a 5’ UTR and translational enhancer sequence as described herein. In some embodiments, a translational enhancer sequence is upstream (5’) of a translation initiation codon. In some embodiments, a translational enhancer sequence immediately precedes a modified Kozak sequence as described herein. In some embodiments, a translational enhancer sequence followed by 5, 4, 3, 2, or 1 nucleotide(s) precedes an attenuated Kozak sequence. In some embodiments, a translational enhancer sequence is selected from a library of sequence translational enhancer sequences. In some embodiments, a translational enhancer sequence is Syn21, AACTTAAAAAAAAAAATCAAA (SEQ ID NO: 25). In some embodiments, a translation enhancer sequence is L21, AACTCCTAAAAAACCGCCACC (SEQ ID NO: 26). In some embodiments, a translation enhancer sequence is AcNPV, AATTACAAATTATATAACAAA (SEQ ID NO: 27). In some embodiments, a translation enhancer sequence is EoNPV, TACGGTGTATTTTAGATTTCACAAACAATTACGAAAGGACTACAATACT (SEQ ID NO: 28). In some embodiments, a translation enhancer sequence is TMV, GTATTTTTACAACAATTACCAACAACAACAAACAACAAACAACATTACAATTACT ATTTACAATTACA (SEQ ID NO: 29).
[0066] In some embodiments, a AAV Rep sequence comprises a 5’ UTR and translational enhancer sequence as described herein. In some embodiments, a translational enhancer sequence is upstream (5’) of a translation initiation codon. In some embodiments, a translational enhancer sequence immediately precedes a modified Kozak sequence as described herein. In some embodiments, a translational enhancer sequence followed by 5, 4, 3, 2, or 1 nucleotide(s) precedes an attenuated Kozak sequence. In some embodiments, a translational enhancer sequence is selected from a library of sequence translational enhancersequences. In some embodiments, a translational enhancer sequence is Syn21, AACTTAAAAAAAAAAATCAAA (SEQ ID NO: 25). In some embodiments, a translation enhancer sequence is L21, AACTCCTAAAAAACCGCCACC (SEQ ID NO: 26). In some embodiments, a translation enhancer sequence is AcNPV, AATTACAAATTATATAACAAA (SEQ ID NO: 27). In some embodiments, a translation enhancer sequence is EoNPV, TACGGTGTATTTTAGATTTCACAAACAATTACGAAAGGACTACAATACT (SEQ ID NO: 28). In some embodiments, a translation enhancer sequence is TMV, GTATTTTTACAACAATTACCAACAACAACAAACAACAAACAACATTACAATTACT ATTTACAATTACA (SEQ ID NO: 29).5’ Untranslated Region (5’ UTR)
[0067] One of skill in the art will understand sequence elements associated with translation of eukaryotic RNA. One of skill in the art will understand a 5’ untranslated region (5 ’UTR) is a region of RNA upstream from an initiation codon.
[0068] In some embodiments, a 5 ’UTR comprises a region upstream of a Cap sequence initiation codon. In some embodiments, a 5’ UTR comprises a region upstream of an attenuated Kozak sequence that immediately precedes a Cap sequence initiation codon. In some embodiments, a 5’ UTR comprises a region upstream of a translational enhancer sequence that immediate precedes an attenuated Kozak sequence, wherein an attenuated Kozak sequence immediately precedes a Cap sequence initiation codon. In some embodiments, a 5’ UTR comprises a region between a translational enhancer sequence and an attenuated Kozak sequence, wherein an attenuated Kozak sequence immediately precedes a Cap sequence initiation codon. In some embodiments, a 5 ’UTR comprises a region between an attenuated Kozak sequence and a Cap sequence initiation codon.
[0069] In some embodiments, a ’UTR comprises a region upstream of a Rep sequence initiation codon. In some embodiments, a 5’ UTR comprises a region upstream of an attenuated Kozak sequence that immediately precedes a Rep sequence initiation codon. In some embodiments, a 5’ UTR comprises a region upstream of a translational enhancer sequence that immediate precedes an attenuated Kozak sequence, wherein an attenuated Kozak sequence immediately precedes a Rep sequence initiation codon. In someembodiments, a 5’ UTR comprises a region between a translational enhancer sequence and an attenuated Kozak sequence, wherein an attenuated Kozak sequence immediately precedes a Rep sequence initiation codon. In some embodiments, a 5 ’UTR comprises a region between an attenuated Kozak sequence and a Rep sequence initiation codon.Methods of AAV Production
[0070] Among other things, compositions and methods as described herein are useful in methods of producing AAV (e.g., rAAV). In some embodiments, rAAV is produced by transfection of a producer cell. In some embodiments, a producer cell is an insect cell. In some embodiments, a producer cell is a transformed insect cell. In some embodiments, a producer cell is an Sf9 cell or derivative thereof.
[0071] In some embodiments, a method of producing rAAV comprises transfection of a producer cell with an AAV vector plasmid and an AAV Rep-Cap plasmid as described herein. In some embodiments, an AAV vector plasmid comprises AAV inverted terminal repeats (ITRs) and a transgene of interest. In some embodiments, plasmids as described herein (e.g., those useful in the production of AAV) are baculovirus expression vectors (BEVs).
[0072] In some embodiments, a method of producing rAAV comprises transfection of a producer cell stably expressing Rep-Cap wherein the nucleotide sequence encoding Cap comprises a 5 ’UTR, a modified Kozak sequence and / or a translational enhancer sequence as described herein. In some embodiments, a method of producing rAAV comprises transfection of a producer cell stably expressing Rep-Cap wherein the nucleotide sequence encoding Rep comprises a modified Kozak sequence and / or a translational enhancer sequence as described herein. In some embodiments, a method of producing rAAV comprises transfection of a producer cell stably expressing Rep-Cap wherein the nucleotide sequence encoding Cap and the nucleotide sequence encoding Rep each comprise a 5 ’UTR, a modified Kozak sequence and / or a translational enhancer sequence as described herein. In some embodiments, a method of producing rAAV comprises transfection of a producer cell stably expressing Rep-Cap with an AAV vector plasmid.
[0073] In some embodiments, rAAV production efficiency is evaluated by assaying for protein expression (e.g., Jess Western Simple System). In some embodiments, AAV production efficiency is evaluated by assaying for capsid protein expression. In some embodiments, rAAV production is evaluated by assaying for VP1, VP2, and / or VP3 protein expression. In some embodiments, rAAV production is evaluated by determining the ratio of VP1 to VP2 to VP3 protein expression. In some embodiments, rAAV production is evaluated by assaying for Rep78 and / or Rep52 protein expression.
[0074] Among other things, the present disclosure describes introducing modified Kozak sequences in a producer cell for capsid protein expression. Among other things, the present disclosure describes introducing modified Kozak sequences in a producer cell for Rep protein expression. One of skill in the art will appreciate that modified Kozak sequences as described herein can relate to an AAV Rep-Cap plasmid or a producer cell stably expressing Rep-Cap.
[0075] Among other things, the present disclosure describes introducing translational enhancer sequences in a producer cell for capsid protein expression. Among other things, the present disclosure describes introducing translational enhancer sequences in a producer cell for Rep protein expression. One of skill in the art will appreciate that translational enhancer sequences as described herein can relate to an AAV Rep-Cap plasmid or a producer cell stably expressing Rep-Cap.AAV Cap Sequences
[0076] Among other things, the present disclosure provides Cap sequences useful in the production of rAAV.
[0077] One of skill in the art will appreciate that a viral capsid is a protein-based structure for the encapsulation of viral nucleic acid. An AAV capsid comprises VP1, VP2, VP3 capsid proteins. Cellular expression of an AAV Cap sequence (e.g., as described herein) can result in AAV capsid formation.
[0078] In some embodiments, an AAV capsid is derived from AAV serotype. In some embodiments, an AAV capsid is derived from AAV5. In some embodiments, an AAVcapsid consists of VP1, VP2, and VP3 capsid proteins derived from AAV5 serotype. In some embodiments, an AAV capsid consists of modified VP1, VP2, and / or VP3 capsid proteins (e.g., one or more VP capsid proteins are modified to comprise one or more amino acid substitutions, deletions, or additions) derived from AAV5 serotype.
[0079] Among other things, the present disclosure provides a nucleic acid molecule encoding adeno-associated virus (AAV) Cap, wherein the nucleic acid molecule comprises a 5’ UTR and a modified Kozak sequence selected from SEQ ID NOs: 2-21. In some embodiments, the modified Kozak sequence is attenuated. In some embodiments, the attenuated Kozak sequence has a translation efficiency less than a wild type, or canonical Kozak sequence.
[0080] In some embodiments, the present disclosure provides a nucleic acid molecule encoding an adeno-associated virus (AAV) Cap, wherein the nucleic acid molecule comprises a 5’ UTR and a modified Kozak sequence selected from SEQ ID NOs: 2-21. In some embodiments, the nucleic acid molecule further comprises a translational enhancer sequence. In some embodiments, the translational enhancer sequence is selected from Syn21 (SEQ ID NO: 25), L21 (SEQ ID NO: 26), AcNPV (SEQ ID NO: 27), EoNPV (SEQ ID NO: 28), TMV (SEQ ID NO: 29).
[0081] In some embodiments, the present disclosure provides a method of producing recombinant AAV (rAAV) particles comprising the nucleic acid molecule in a producer cell. In some embodiments, the producer cell is an insect cell. In some embodiments, the producer cell is Sf9 or a derivative cell line thereof. In some embodiments, the rAAV capsid is derived from AAV serotype 5 (AAV5).
[0082] In some embodiments, the present disclosure provides a nucleic acid molecule encoding adeno-associated virus (AAV) Cap, wherein the nucleic acid molecule comprises a 5’UTR and a translational enhancer sequence selected from SEQ ID NOs: 25- 29. In some embodiments, the nucleic acid molecule further comprises a modified Kozak sequence selected from SEQ ID NOs: 2-21.AAV Rep Sequences
[0083] Among other things, the present disclosure provides Rep sequences useful in the production of rAAV.
[0084] Without wishing to be bound by any particular theory, in some embodiments, overexpression of Rep proteins may decrease AAV yield. In some embodiments, overexpression of Rep52 may decrease AAV yield. In some embodiments, overexpression of Rep78 may decrease AAV yield. In some embodiments, the present disclosure provides compositions and methods that regulate expression of Rep and increase AAV yield.
[0085] In some embodiments, an AAV Rep gene derived from AAV serotype. In some embodiments, an AAV Rep gene is derived from AAV2. In some embodiments, an AAV Rep gene comprises a Rep78 encoding sequence and a Rep52 encoding sequence.
[0086] Among other things, the present disclosure provides a nucleic acid molecule encoding adeno-associated virus (AAV) Rep, wherein the nucleic acid molecule comprises a modified Kozak sequence selected from SEQ ID NOs: 2-21. In some embodiments, the present disclosure provides a nucleic acid molecule encoding adeno-associated virus (AAV) Rep, wherein the nucleic acid molecule comprises a modified Kozak sequence that is or comprises SEQ ID NO:8. In some embodiments, the modified Kozak sequence is attenuated. In some embodiments, the attenuated Kozak sequence has a translation efficiency less than a wild type, or canonical Kozak sequence. In some embodiments, the nucleic acid molecule further comprises a translational enhancer sequence. In some embodiments, the translational enhancer sequence is selected from Syn21 (SEQ ID NO: 25), L21 (SEQ ID NO: 26), or AcNPV (SEQ ID NO: 27). In some embodiments, a nucleic acid molecule encoding adeno-associated virus (AAV) Rep further comprises a 5’ UTR.
[0087] In some embodiments, the present disclosure provides a method of producing recombinant AAV (rAAV) particles comprising the nucleic acid molecule in a producer cell. In some embodiments, the producer cell is an insect cell. In some embodiments, the producer cell is Sf9 or a derivative cell line thereof. In some embodiments, Rep derived from AAV serotype 2 (AAV2).
[0088] In some embodiments, the present disclosure provides a nucleic acid molecule encoding adeno-associated virus (AAV) Rep, wherein the nucleic acid molecule comprises a translational enhancer sequence selected from SEQ ID NOs: 25-27. In someembodiments, the nucleic acid molecule further comprises a modified Kozak sequence that is or comprises SEQ ID NO: 8.EXEMPLIFICATIONExample 1: Selection of Exemplary Attenuated Kozak Sequences
[0089] The present example describes selection of exemplary modified Kozak sequences for use in AAV production.
[0090] To select attenuated Kozak sequences for use in recombinant AAV production (e.g., rAAV production methods as described herein), selection criteria were applied to an initial list of sequences as defined by the consensus of NNNNNNAUGNN (SEQ ID NO: 22) having 65,536 possible variants. Then, sequences were selected to fit the consensus of RNXUXUAUGNY (SEQ ID NO: 23) and to have a predicted efficiency between 35% and 45%, resulting in a shortened list having 53 possible variants. “R” denotes U or C; “N” denotes A, G, C, or U; ‘’X” denotes U or G; “Y” denotes A, C, or U; and “Z?’ denotes G or C. Next, sequences were selected to fit the consensus of RNXUXUAUGUC (SEQ ID NO: 24), resulting in a shortened list having 20 possible variants (Figure 3). UGUUUUAUGUC (SEQ ID NO: 1) was selected for further rAAV production experiments as a positive control. Four sequences were selected for further rAAV production experiments (Figure 3).Example 2: Exemplary Attenuated Kozak Sequences for AAV5 Capsid Protein Expression
[0091] The present example describes use of Rep-Cap plasmids comprising exemplary attenuated Kozak sequences in the production of rAAV from Sf9 cells. A list of exemplary attenuated Kozak sequences are shown in Table 1.Table 1 : Exemplified Attenuated Kozak sequences.
[0092] Five Kozak sequences were selected for experimentation in r AAV production. The five sequences are as follows: UGUUUUAUGUC (SEQ ID NO: 1), UUUUUUAUGUC (SEQ ID NO: 2), UAUUUUAUGUC (SEQ ID NO: 8), CGUUUUAUGUC (SEQ ID NO: 17), and UGGUUUAUGUC (SEQ ID NO: 21). Kozak sequences were cloned into pFBac-Rep2Cap5 plasmid for the production of AAV5, and plasmids were named based on the theoretical efficiency associated with a particular Kozak sequence (Figure 4). pFBac-Rep2Cap5-40CB comprises UGUUUUAUGUC (SEQ ID NO: 1), pFBac-Rep2Cap5-35B comprises UGGUUUAUGUC (SEQ ID NO: 21), pFBac- Rep2Cap5-37B comprises CGUUUUAUGUC (SEQ ID NO: 17), pFBac-Rep2Cap5-40B comprises UAUUUUAUGUC (SEQ ID NO: 8), and pFBac-Rep2Cap5-44B comprises UUUUUUAUGUC (SEQ ID NO: 2). Multiple BEV isolates were acquired for each pFBac- Rep2Cap5 plasmid (e.g., at least ten isolates per plasmid). pFBac-Rep2Cap5 BEV isolates were introduced to Sf9 cells for the production of AAV5. Proteins were harvested from clarified lysate and analysis was performed using a Jess ProteinSimple capillary analysis system to determine AAV5 VP1, VP2, and VP3 expression (Figures 6A-6B).
[0093] Expression of VP2 and VP3 proteins relative to VP1 protein for each BEV isolate of each plasmid is shown in Figure 7. The far right column for each plasmid displays the average relative protein expression across all isolates where protein expression was quantified. All plasmids resulted in the production of capsid proteins. Plasmid 44B resulted in the closest ratio of VP1:VP2:VP3 of 1:1:10.Example 3: Exemplary Translational Enhancer Sequences for AAV5 Capsid Protein Expression.
[0094] The present example describes use of exemplary Rep-Cap plasmids comprising exemplary translational enhancer sequences and attenuated Kozak sequences in the production of rAAV from Sf9 cells.
[0095] Five translation enhancer sequences, Syn21, L21, AcNPV, EoNPV, and TMV, were selected for experimentation in AAV production. The sequences of each of the five tested translation enhancers are as follows: Syn21 comprises AACTTAAAAAAAAAAATCAAA (SEQ ID NO: 25), L21 comprises AACTCCTAAAAAACCGCCACC (SEQ ID NO: 26), AcNPV comprises AATTACAAATTATATAACAAA (SEQ ID NO: 27), EoNPV comprises TACGGTGTATTTTAGATTTCACAAACAATTACGAAAGGACTACAATACT (SEQ ID NO: 28), and TMV comprises GTATTTTTACAACAATTACCAACAACAACAAACAACAAACAACATTACAATTACT ATTTACAATTACA (SEQ ID NO: 29).
[0096] Translation enhancer sequences were cloned upstream of an attenuatedKozak sequence to generate pFBac-Rep2Cap5-40AE and pFBac-Rep2Cap5-40CE plasmids for production of rAAV5. pFBac- Rep2Cap5-40AE comprises an attenuated Kozak sequence UAUUUUAUGUC (SEQ ID NO: 8). pFBac- Rep2Cap5-40CE comprises a Kozak sequence UGUUUUAUGUC (SEQ ID NO: 1). The constructs tested are shown in Table 2.Table 2: Exemplified plasmids described herein comprising a Kozak sequence and a translational enhancer sequence.
[0097] Multiple BEV isolates were acquired for each pFBac-Rep2Cap5 plasmid (e.g., at least ten isolates per plasmid). pFBac-Rep2Cap5 BEV isolates were delivered to Sf9 cells for production of AAV5. Proteins were harvested from clarified lysate and analysis was performed using a Jess ProteinSimple capillary analysis system to determine AAV5 VP1, VP2, and VP3 expression (Figures 8A-8B).
[0098] Plasmids pFBacX-AAVRep2ACap5_40AE AcNPV (SEQ ID NO: 34), pFBacX-AAVRep2ACap5_40AE L21 (SEQ ID NO: 37), and pFBacX- AAVRep2ACap5_40AE Syn21 (SEQ ID NO: 38) resulted in the closest ratio of VP1: VP2: VP3 of 1 : 1 : 10. To expand the titer and yield of AAV production, isolates from each of these plasmids were expanded in 400 mL flasks. Proteins were harvested from clarified lysate and purified by affinity chromatography, followed by a CsCl density gradient. Final formulations were dialyzed into the appropriate buffer and analyzed by capillary gel electrophoresis. The VPEVP2: VP3 ratios relative to VP1 of 40AE AcNPV, 40AE L21, and 40AE Syn21 isolates are shown in Table 3. Final formulation titers and yields are shown in Figure 12.
[0099] Tissue Culture Infectious Dose 50 (TCID50) assay utilized RC32 HeLa cells that express the rep / cap genes necessary for AAV vector assembly and replication, in combination with H5 adenovirus (Ad5). 96- well plates were seeded with RC32 cells andallowed to grow overnight. Co-infection of the plated RC32 cells with Ad5 and serial dilutions of the vector were performed the next day. qPCR measurement of the target analyte, located within the inverted terminal repeats (ITR) of the AAV vector genome DNA, was used to gain titer results. The results generated from qPCR were used to calculate the TC1D50 via the Karber-Spearman method. TCID50 is defined as the tissue culture infectious dose of virus required to infect 50% of the cells. The P:I ratio is calculated by dividing the particle titer by the TCID50 / mL titer is shown in Figure 13.Table 3: Exemplified Ratios of VP proteins.Example 4: Exemplified Combinations of Translational Enhancer Sequences and Attenuated Kozak Sequences for AV5 Capsid Protein Expression.
[0100] The present Example describes introducing exemplary plasmids comprising exemplary translational enhancer sequences in combination with exemplary attenuated Kozak sequences in Sf9 cells to express AAV5 VP1, VP2, and VP3 proteins.
[0101] Three attenuated Kozak sequences are selected for experimentation in AAV production in combination with translation enhancer sequences. The three sequences are as follows: UUUUUUAUGUC (SEQ ID NO: 2), CGUUUUAUGUC (SEQ ID NO: 17), andUGGUUUAUGUC (SEQ ID NO 21). These attenuated Kozak sequences are tested with translation enhancer sequences Syn21 and L21. The constructs that are tested are shown in Table 4.Table 4: Exemplified plasmids described herein comprising an attenuated Kozak sequence and a translational enhancer sequence.
[0102] Multiple BEV isolates are acquired for each pFBacX-AAVRep2ACap5 plasmid (e.g., at least ten isolates per plasmid). pFBacX-AAVRep2ACap5 BEV isolates are delivered to Sf9 cells for production of AAV5. Proteins are harvested from clarified lysate and analysis is performed using a Jess ProteinSimple capillary analysis system to determine AAV5 VP1, VP2, and VP3 expression.
[0103] To expand the titer and yield of AAV production, isolates from each of these plasmids are expanded in 400 mF flasks. Proteins are harvested from clarified lysate and purified by affinity chromatography, followed by a CsCl density gradient. Final formulations are dialyzed into the appropriate buffer and analyzed by capillary gel electrophoresis.Example 5: Exemplified Combinations of Translational Enhancer Sequences and Attenuated Kozak Sequence for Rep Protein Expression.
[0104] The present Example describes introducing exemplary plasmids comprising exemplary translational enhancer sequences in combination with exemplary attenuated Kozak sequences in Sf9 cells to express AAV2 Rep proteins (Figure 14).
[0105] Three translation enhancer sequences were selected for experimentation in AAV Rep production: AcNPV (SEQ ID NO: 27), L21 (SEQ ID NO: 26), and Syn21 (SEQ ID NO: 25). These translational enhancers were each tested in combination with attenuated Kozak sequence UAUUUUAUGUC (SEQ ID NO: 8) upstream of the Rep encoding sequence. The constructs that were tested were pB-40A_Rep2Cap5 (Figure 17), pB- 40L_Rep2Cap5 (Figure 18), pB-40S_Rep2Cap5 (Figure 19), shown in Table 5.Table 5: Exemplified plasmids described herein comprising an attenuated Kozak sequence and a translational enhancer sequence.
[0106] Multiple BEV isolates were acquired for each pB-40-Rep2Cap5 plasmid(e.g., at least ten isolates per plasmid). pB-40-Rep2Cap5 BEV isolates were delivered to Sf9 cells for production of rAAV. Proteins were harvested from clarified lysate and analysis was performed using a Jess Protein Simple capillary analysis system to determine Rep78 and Rep52 expression (Figure 15).
[0107] To expand the titer and yield of AAV production, isolates from each of these plasmids were expanded in 250 mL flasks. Proteins were harvested from clarified lysate and purified by affinity chromatography, followed by a CsCl density gradient. Final formulations were dialyzed into the appropriate buffer and analyzed by capillary gel electrophoresis.
[0108] Final formulation yields are shown in Figure 16. While pB-40L-Rep2Cap5 yield was slightly decreased compared to pFBacX-AAVRep2ACap5_40AE L21, both pB- 40A-Rep2Cap5 and pB-40S-Rep2Cap5 constructs had increased yield.EXEMPLARY SEQUENCES
[0109] The following list provides exemplary amino acid and nucleic acid sequences as described herein. pFBacX-AAVRep2ACap5_35AE L21 (SEQ ID NO: 30) tcgcgcgtttcggtgatgacggtgaaaacctctgacacatgcagctcccggagacggtcacagcttgtctgtaagcggatgccggga gcagacaagcccgtcagggcgcgtcagcgggtgttggcgggtgtcggggctggcttaactatgcggcatcagagcagattgtact gagagtgcaccatatgcggtgtgaaataccgcacagatgcgtaaggagaaaataccgcatcaggcgccattcgccattcaggctgc gcaactgttgggaagggcgatcggtgcgggcctcttcgctattacgccagctggcgaaagggggatgtgctgcaaggcgattaagt tgggtaacgccagggttttcccagtcacgacgttgtaaaacgacggccagtgaattcgagctcggtacctcgcgaatgcatctagat GATTAAAAACATAACAGGAAGAAAAATGCCCCGCTGTGGGCGGACAAAATAGTT GGGAACTGGGAGGGGTGGAAATGGAGTTTTTAAGGATTATTTAGGGAAGAGTGA CAAAATAGATGGGAACTGGGTGTAGCGTCGTAAGCTAATACGAAAATTAAAAATG ACAAAATAGTTTGGAACTAGATTTCACTTATCTGGTTcggatctgggtccccctaggctcaagcagt gatcagatccagacatgataagatacattgatgagtttggacaaaccacaactagaatgcagtgaaaaaaatgctttatttgtgaaattt gtgatgctattgctttatttgtaaccattataagctgcaataaacaagttaacaacaacaattgcattcattttatgtttcaggttcaggggga ggtgtgggaggttttttaaagcaagtaaaacctctacaaatgtggtatggctgattatgatcctctagtacttctcgacaagcttgtcgag actgcaggctctagagtcgacctgcaggcatgcaagcttgattcctcgagtttattgttcaaagatgcagtcatccaaatccacattgac cagatcgcaggcagtgcaagcgtctggcacctttcccatgatatgatgaatgtagcacagtttctgatacgcctttttgacgacagaaa cgggttgagattctgacacgggaaagcactctaaacagtctttctgtccgtgagtgaagcagatatttgaattctgattcattctctcgcat tgtctgcagggaaacagcatcagattcatgcccacgtgacgagaacatttgttttggtacctgtctgcgtagttgatcgaagcttccgcg tctgacgtcgatggctgcgcaactgactcgcgcacccgtttgggctcacttatatctgcgtcactgggggcgggtcttttcttggctcca ccctttttgacgtagaattcatgctccacctcaaccacgtgatcctttgcccaccggaaaaagtctttgacttcctgcttggtgaccttccc aaagtcatgatccagacggcgggtgagttcaaatttgaacatccggtcttgcaacggctgctggtgttcgaaggtcgttgagttcccgt caatcacggcgcacatgttggtgttggaggtgacgatcacgggagtcgggtctatctgggccgaggacttgcatttctggtccacgc gcaccttgcttcctccgagaatggctttggccgactccacgaccttggcggtcatcttcccctcctcccaccagatcaccatcttgtcga cacagtcgttgaagggaaagttctcattggtccagtttacgcacccgtagaagggcacagtgtgggctatggcctccgcgatgttggt cttcccggtagttgcaggcccaaacagccagatggtgttcctcttgccgaactttttcgtggcccatcccagaaagacggaagccgca tattggggatcgtacccgtttagttccaaaattttataaatccgattgctggaaatgtcctccacgggctgctggcccaccaggtagtcg ggggcggttttagtcaggctcataatctttcccgcattgtccaaggcagccttgatttgggaccgcgagttggaggccgcattgaagg agatgtatgaAgcctggtcctcctggatccactgcttctccgaggtaatccccttgtccacgagccacccgaccagctccatgtacct ggctgaagtttttgatctgatcaccggcgcgtcagaattgggattctgattctctttgttctgctcctgcgtctgcgacacgtgcgtcagat gctgcgccaccaaccgtttacgctccgtgagattcaaacaggcgcttaaatactgttctaaattagtccacgcccactggagctcagg ctgggttttggggagcaagtaattggggatgtagcactcgtccaccaccttgttcccgcctccggcgccgtttctggtctttgtgaccgc gaaccagtttggcaaagtcggctcgatcccgcggtaaattctctgaatcagtttttcgcgaatctgactcaggaaacgtcccaaaacta aggatttcaccccggtggtttccacgagcacgtgtaagtggaagtagctctctcccttctcaaattgcacaaagaaaagggcctccgg ggccttactcacacggcgccactccgtcagaaagtcgcgctgcagcttctcggccacggtcaggggtgcctgctcaatcagattcag atccaagtcagaatctggcggcaactcccactccttctcggccacccagttcacaaagctgtcagaaatgccgggcagatgctcgtc aaggtcgctggggaccttaatcacaatctcgtaaaaccccgccagggcggcagatccgcgcccgatggtGCGGCCGCacg gtatgaataatccggaatatttataggtttttttattacaaaactgttacgaaaacagtaaaatacttatttatttgcgagatggttatcatttta attatctccatgatctattaatattcACGCGTcggagtatacggacctttaattcaacccaacacaatatattatagttaaataagaatt attatcaaatcatttgtatattaattaaaatactatactgtaaattacattttatttacaatcaatactagtaaaaggtaggttcaaccactgatg cctaggcacaccgaaacgactaaccctaattcttatcctttacttcaggcgcgcccggcttaagcgtacgAACTCCTAAAAAACCGCCACCTggTTTatgtcttttgttgatcaccctccagattggttggaagaagttggtgaaggtcttcgcgagtttttgg gccttgaagcgggcccaccgaaaccaaaacccaatcagcagcatcaagatcaagcccgtggtcttgtgctgcctggttataactatct cggacccggaaacggtctcgatcgaggagagcctgtcaacagggcagacgaggtcgcgcgagagcacgacatctcgtacaacgagcagcttgaggcgggagacaacccctacctcaagtacaaccacgcggacgccgagtttcaggagaagctcgccgacgacacat ccttcgggggaaacctcggaaaggcagtctttcaggccaagaaaagggttctcgaaccttttggcctggttgaagagggtgctaaga cggcccctaccggaaagcggatagacgaccactttccaaaaagaaagaaggctcggaccgaagaggactccaagccttccacctc gtcagacgccgaagctggacccagcggatcccagcagctgcaaatcccagcccaaccagcctcaagtttgggagctgatacaatg tctgcgggaggtggcggcccattgggcgacaataaccaaggtgccgatggagtgggcaatgcctcgggagattggcattgcgatt ccacgtggatgggggacagagtcgtcaccaagtccacccgaacctgggtgctgcccagctacaacaaccaccagtaccgagagat caaaagcggctccgtcgacggaagcaacgccaacgcctactttggatacagcaccccctgggggtactttgactttaaccgcttcca cagccactggagcccccgagactggcaaagactcatcaacaactactggggcttcagaccccggtccctcagagtcaaaatcttca acattcaagtcaaagaggtcacggtgcaggactccaccaccaccatcgccaacaacctcacctccaccgtccaagtgtttacggacg acgactaccagctgccctacgtcgtcggcaacgggaccgagggatgcctgccggccttccctccgcaggtctttacgctgccgcag tacggttacgcgacgctgaaccgcgacaacacagaaaatcccaccgagaggagcagcttcttctgcctagagtactttcccagcaa gatgctgagaacgggcaacaactttgagtttacctacaactttgaggaggtgcccttccactccagcttcgctcccagtcagaacctctt caagctggccaacccgctggtggaccagtacttgtaccgcttcgtgagcacaaataacactggcggagtccagttcaacaagaacct ggccgggagatacgccaacacctacaaaaactggttcccggggcccatgggccgaacccagggctggaacctgggctccgggg tcaaccgcgccagtgtcagcgccttcgccacgaccaataggatggagctcgagggcgcgagttaccaggtgcccccgcagccga acggcatgaccaacaacctccagggcagcaacacctatgccctggagaacactatgatcttcaacagccagccggcgaacccggg caccaccgccacgtacctcgagggcaacatgctcatcaccagcgagagcgagacgcagccggtgaaccgcgtggcgtacaacgt cggcgggcagatggccaccaacaaccagagctccaccactgcccccgcgaccggcacgtacaacctccaggaaatcgtgcccg gcagcgtgtggatggagagggacgtgtacctccaaggacccatctgggccaagatcccagagacgggggcgcactttcacccctc tccggccatgggcggattcggactcaaacacccaccgcccatgatgctcatcaagaacacgcctgtgcccggaaatatcaccagctt ctcggacgtgcccgtcagcagcttcatcacccagtacagcaccgggcaggtcaccgtggagatggagtgggagctcaagaagga aaactccaagaggtggaacccagagatccagtacacaaacaactacaacgacccccagtttgtggactttgccccggacagcaccg gggaatacagaaccaccagacctatcggaacccgataccttacccgacccctttaagctagcagctgatgcatagcatgcggtaccg ggagatgggggaggctaactgaaacacggaaggagacaataccggaaggaacccgcgctatgacggcaataaaaagacagaat aaaacgcacgggtgttgggtcgtttgttcGAGTCATTTAAATACCGGTCTGGGCGAACAAACGATG CTCGCCTTCCAGAAAACCGAGGATGCGAACCACTTCATCCGGGGTCAGCACCAC CGGCAAGCGCCGCGACGGCCGAGGTCTTCCGATCTCCTGAAGCCAGGGCAGATC CGTGCACAGCACCTTGCCGTAGAAGAACAGCAAGGCCGCCAATGCCTGACGATG CGTGGAGACCGAAACCTTGCGCTCGTTCGCCAGCCAGGACAGAAATGCCTCGAC TTCGCTGCTGCCCAAGGTTGCCGGGTGACGCACACCGTGGAAACGGATGAAGGC ACGAACCCAGTTGACATAAGCCTGTTCGGTTCGTAAACTGTAATGCAAGTAGCGT ATGCGCTCACGCAACTGGTCCAGAACCTTGACCGAACGCAGCGGTGGTAACGGC GCAGTGGCGGTTTTCATGGCTTGTTATGACTGTTTTTTTGTACAGTCTATGCCTCG GGCATCCAAGCAGCAAGCGCGTTACGCCGTGGGTCGATGTTTGATGTTATGGAGC AGCAACGATGTTACGCAGCAGCAACGATGTTACGCAGCAGGGCAGTCGCCCTAA AACAAAGTTAGGTGGCTCAAGTATGGGCATCATTCGCACATGTAGGCTCGGCCCT GACCAAGTCAAATCCATGCGGGCTGCTCTTGATCTTTTCGGTCGTGAGTTCGGAG ACGTAGCCACCTACTCCCAACATCAGCCGGACTCCGATTACCTCGGGAACTTGCT CCGTAGTAAGACATTCATCGCGCTTGCTGCCTTCGACCAAGAAGCGGTTGTTGGC GCTCTCGCGGCTTACGTTCTGCCCAAGTTTGAGCAGCCGCGTAGTGAGATCTATAT CTATGATCTCGCAGTCTCCGGCGAGCACCGGAGGCAGGGCATTGCCACCGCGCT CATCAATCTCCTCAAGCATGAGGCCAACGCGCTTGGTGCTTATGTGATCTACGTGC AAGCAGATTACGGTGACGATCCCGCAGTGGCTCTCTATACAAAGTTGGGCATACG GGAAGAAGTGATGCACTTTGATATCGACCCAAGTACCGCCACCTAACAATTCGTT CAAGCCGAGATCGGCTTCCCGGCCGCGGAGTTGTTCGGTAAATTGTCACAACGC CGCGAATATAGTCTTTACCATGCCCTTGGCCACGCCCCTCTTTAATACGACGGGCA ACT TT TT TG TTC CA AC CT ATC GA CG ATA AA AA CA TT GG GA AA CG TA GG AT TT TT TG CC AT GT TT TA TG AC CC AA AT CA TA AC TA TA CA TGA TG CT TC AC GA TG TT TA AT AG GACTTTATTGTCATAGTTTAGATCTATTTTGTTCAGTTTAAGACTTTATTGTCCGCCCACACCCGCTTACGCAGGGCATCCATTTATTACTCAAatcggatcccgggcccgtcgactgcagag gcctgcatgcaagcttggcgtaatcatggtcatagctgtttcctgtgtgaaattgttatccgctcacaattccacacaacatacgagccg gaagcataaagtgtaaagcctggggtgcctaatgagtgagctaactcacattaattgcgttgcgctcactgcccgctttccagtcggga aacctgtcgtgccagctgcattaatgaatcggccaacgcgcggggagaggcggtttgcgtattgggcgctcttccgcttcctcgctca ctgactcgctgcgctcggtcgttcggctgcggcgagcggtatcagctcactcaaaggcggtaatacggttatccacagaatcagggg ataacgcaggaaagaacatgtgagcaaaaggccagcaaaaggccaggaaccgtaaaaaggccgcgttgctggcgtttttccatag gctccgcccccctgacgagcatcacaaaaatcgacgctcaagtcagaggtggcgaaacccgacaggactataaagataccaggc gtttccccctggaagctccctcgtgcgctctcctgttccgaccctgccgcttaccggatacctgtccgcctttctcccttcgggaagcgt ggcgctttctcatagctcacgctgtaggtatctcagttcggtgtaggtcgttcgctccaagctgggctgtgtgcacgaaccccccgttca gcccgaccgctgcgccttatccggtaactatcgtcttgagtccaacccggtaagacacgacttatcgccactggcagcagccactgg taacaggattagcagagcgaggtatgtaggcggtgctacagagttcttgaagtggtggcctaactacggctacactagaagaacagt atttggtatctgcgctctgctgaagccagttaccttcggaaaaagagttggtagctcttgatccggcaaacaaaccaccgctggtagcg gtggtttttttgtttgcaagcagcagattacgcgcagaaaaaaaggatctcaagaagatcctttgatcttttctacggggtctgacgctca gtggaacgaaaactcacgttaagggattttggtcatgagattatcaaaaaggatcttcacctagatccttttaaattaaaaatgaagtttta aatcaatctaaagtatatatgagtaaacttggtctgacagttaccaatgcttaatcagtgaggcacctatctcagcgatctgtctatttcgtt catccatagttgcctgactccccgtcgtgtagataactacgatacgggagggcttaccatctggccccagtgctgcaatgataccgcg agacccacgctcaccggctccagatttatcagcaataaaccagccagccggaagggccgagcgcagaagtggtcctgcaactttat ccgcctccatccagtctattaattgttgccgggaagctagagtaagtagttcgccagttaatagtttgcgcaacgttgttgccattgctac aggcatcgtggtgtcacgctcgtcgtttggtatggcttcattcagctccggttcccaacgatcaaggcgagttacatgatcccccatgtt gtgcaaaaaagcggttagctccttcggtcctccgatcgttgtcagaagtaagttggccgcagtgttatcactcatggttatggcagcact gcataattctcttactgtcatgccatccgtaagatgcttttctgtgactggtgagtactcaaccaagtcattctgagaatagtgtatgcggc gaccgagttgctcttgcccggcgtcaatacgggataataccgcgccacatagcagaactttaaaagtgctcatcattggaaaacgttct tcggggcgaaaactctcaaggatcttaccgctgttgagatccagttcgatgtaacccactcgtgcacccaactgatcttcagcatctttt actttcaccagcgtttctgggtgagcaaaaacaggaaggcaaaatgccgcaaaaaagggaataagggcgacacggaaatgttgaat actcatactcttcctttttcaatattattgaagcatttatcagggttattgtctcatgagcggatacatatttgaatgtatttagaaaaataaaca aataggggttccgcgcacatttccccgaaaagtgccacctgacgtctaagaaaccattattatcatgacattaacctataaaaataggc gtatcacgaggccctttcgtc pFBacX-AAVRep2ACap5_35AE Syn21 (SEQ ID NO:31) tcgcgcgtttcggtgatgacggtgaaaacctctgacacatgcagctcccggagacggtcacagcttgtctgtaagcggatgccggga gcagacaagcccgtcagggcgcgtcagcgggtgttggcgggtgtcggggctggcttaactatgcggcatcagagcagattgtact gagagtgcaccatatgcggtgtgaaataccgcacagatgcgtaaggagaaaataccgcatcaggcgccattcgccattcaggctgc gcaactgttgggaagggcgatcggtgcgggcctcttcgctattacgccagctggcgaaagggggatgtgctgcaaggcgattaagt tgggtaacgccagggttttcccagtcacgacgttgtaaaacgacggccagtgaattcgagctcggtacctcgcgaatgcatctagat GATTAAAAACATAACAGGAAGAAAAATGCCCCGCTGTGGGCGGACAAAATAGTT GGGAACTGGGAGGGGTGGAAATGGAGTTTTTAAGGATTATTTAGGGAAGAGTGA CAAAATAGATGGGAACTGGGTGTAGCGTCGTAAGCTAATACGAAAATTAAAAATG ACAAAATAGTTTGGAACTAGATTTCACTTATCTGGTTcggatctgggtccccctaggctcaagcagt gatcagatccagacatgataagatacattgatgagtttggacaaaccacaactagaatgcagtgaaaaaaatgctttatttgtgaaattt gtgatgctattgctttatttgtaaccattataagctgcaataaacaagttaacaacaacaattgcattcattttatgtttcaggttcaggggga ggtgtgggaggttttttaaagcaagtaaaacctctacaaatgtggtatggctgattatgatcctctagtacttctcgacaagcttgtcgag actgcaggctctagagtcgacctgcaggcatgcaagcttgattcctcgagtttattgttcaaagatgcagtcatccaaatccacattgac cagatcgcaggcagtgcaagcgtctggcacctttcccatgatatgatgaatgtagcacagtttctgatacgcctttttgacgacagaaa cgggttgagattctgacacgggaaagcactctaaacagtctttctgtccgtgagtgaagcagatatttgaattctgattcattctctcgcat tgtctgcagggaaacagcatcagattcatgcccacgtgacgagaacatttgttttggtacctgtctgcgtagttgatcgaagcttccgcg tctgacgtcgatggctgcgcaactgactcgcgcacccgtttgggctcacttatatctgcgtcactgggggcgggtcttttcttggctccaccctttttgacgtagaattcatgctccacctcaaccacgtgatcctttgcccaccggaaaaagtctttgacttcctgcttggtgaccttccc aaagtcatgatccagacggcgggtgagttcaaatttgaacatccggtcttgcaacggctgctggtgttcgaaggtcgttgagttcccgt caatcacggcgcacatgttggtgttggaggtgacgatcacgggagtcgggtctatctgggccgaggacttgcatttctggtccacgc gcaccttgcttcctccgagaatggctttggccgactccacgaccttggcggtcatcttcccctcctcccaccagatcaccatcttgtcga cacagtcgttgaagggaaagttctcattggtccagtttacgcacccgtagaagggcacagtgtgggctatggcctccgcgatgttggt cttcccggtagttgcaggcccaaacagccagatggtgttcctcttgccgaactttttcgtggcccatcccagaaagacggaagccgca tattggggatcgtacccgtttagttccaaaattttataaatccgattgctggaaatgtcctccacgggctgctggcccaccaggtagtcg ggggcggttttagtcaggctcataatctttcccgcattgtccaaggcagccttgatttgggaccgcgagttggaggccgcattgaagg agatgtatgaAgcctggtcctcctggatccactgcttctccgaggtaatccccttgtccacgagccacccgaccagctccatgtacct ggctgaagtttttgatctgatcaccggcgcgtcagaattgggattctgattctctttgttctgctcctgcgtctgcgacacgtgcgtcagat gctgcgccaccaaccgtttacgctccgtgagattcaaacaggcgcttaaatactgttctaaattagtccacgcccactggagctcagg ctgggttttggggagcaagtaattggggatgtagcactcgtccaccaccttgttcccgcctccggcgccgtttctggtctttgtgaccgc gaaccagtttggcaaagtcggctcgatcccgcggtaaattctctgaatcagtttttcgcgaatctgactcaggaaacgtcccaaaacta aggatttcaccccggtggtttccacgagcacgtgtaagtggaagtagctctctcccttctcaaattgcacaaagaaaagggcctccgg ggccttactcacacggcgccactccgtcagaaagtcgcgctgcagcttctcggccacggtcaggggtgcctgctcaatcagattcag atccaagtcagaatctggcggcaactcccactccttctcggccacccagttcacaaagctgtcagaaatgccgggcagatgctcgtc aaggtcgctggggaccttaatcacaatctcgtaaaaccccgccagggcggcagatccgcgcccgatggtGCGGCCGCacg gtatgaataatccggaatatttataggtttttttattacaaaactgttacgaaaacagtaaaatacttatttatttgcgagatggttatcatttta attatctccatgatctattaatattcACGCGTcggagtatacggacctttaattcaacccaacacaatatattatagttaaataagaatt attatcaaatcatttgtatattaattaaaatactatactgtaaattacattttatttacaatcaatactagtaaaaggtaggttcaaccactgatg cctaggcacaccgaaacgactaaccctaattcttatcctttacttcaggcgcgcccggcttaagcgtacgaacttaaaaaaaaaaatca aatTGgTTTatgtcttttgttgatcaccctccagattggttggaagaagttggtgaaggtcttcgcgagtttttgggccttgaagcgg gcccaccgaaaccaaaacccaatcagcagcatcaagatcaagcccgtggtcttgtgctgcctggttataactatctcggacccggaa acggtctcgatcgaggagagcctgtcaacagggcagacgaggtcgcgcgagagcacgacatctcgtacaacgagcagcttgagg cgggagacaacccctacctcaagtacaaccacgcggacgccgagtttcaggagaagctcgccgacgacacatccttcgggggaa acctcggaaaggcagtctttcaggccaagaaaagggttctcgaaccttttggcctggttgaagagggtgctaagacggcccctaccg gaaagcggatagacgaccactltccaaaaagaaagaaggctcggaccgaagaggactccaagGcttccacctcgtcagacgccg aagctggacccagcggatcccagcagctgcaaatcccagcccaaccagcctcaagtttgggagctgatacaatgtctgcgggaggt ggcggcccattgggcgacaataaccaaggtgccgatggagtgggcaatgcctcgggagattggcattgcgattccacgtggatgg gggacagagtcgtcaccaagtccacccgaacctgggtgctgcccagctacaacaaccaccagtaccgagagatcaaaagcggct ccgtcgacggaagcaacgccaacgcctactttggatacagcaccccctgggggtactttgactttaaccgcttccacagccactgga gcccccgagactggcaaagactcatcaacaactactggggcttcagaccccggtccctcagagtcaaaatcttcaacattcaagtca aagaggtcacggtgcaggactccaccaccaccatcgccaacaacctcacctccaccgtccaagtgtttacggacgacgactaccag ctgccctacgtcgtcggcaacgggaccgagggatgcctgccggccttccctccgcaggtctttacgctgccgcagtacggttacgc gacgctgaaccgcgacaacacagaaaatcccaccgagaggagcagcttcttctgcctagagtactttcccagcaagatgctgagaa cgggcaacaactttgagtttacctacaactttgaggaggtgcccttccactccagcttcgctcccagtcagaacctcttcaagctggcc aacccgctggtggaccagtacttgtaccgcttcgtgagcacaaataacactggcggagtccagttcaacaagaacctggccgggag atacgccaacacctacaaaaactggttcccggggcccatgggccgaacccagggctggaacctgggctccggggtcaaccgcgc cagtgtcagcgccttcgccacgaccaataggatggagctcgagggcgcgagttaccaggtgcccccgcagccgaacggcatgac caacaacctccagggcagcaacacctatgccctggagaacactatgatcttcaacagccagccggcgaacccgggcaccaccgc cacgtacctcgagggcaacatgctcatcaccagcgagagcgagacgcagccggtgaaccgcgtggcgtacaacgtcggcgggc agatggccaccaacaaccagagctccaccactgcccccgcgaccggcacgtacaacctccaggaaatcgtgcccggcagcgtgt ggatggagagggacgtgtacctccaaggacccatctgggccaagatcccagagacgggggcgcactttcacccctctccggccat gggcggattcggactcaaacacccaccgcccatgatgctcatcaagaacacgcctgtgcccggaaatatcaccagcttctcggacg tgcccgtcagcagcttcatcacccagtacagcaccgggcaggtcaccgtggagatggagtgggagctcaagaaggaaaactccaa gaggtggaacccagagatccagtacacaaacaactacaacgacccccagtttgtggactttgccccggacagcaccggggaatac agaaccaccagacctatcggaacccgataccttacccgacccctttaagctagcagctgatgcatagcatgcggtaccgggagatg ggggaggctaactgaaacacggaaggagacaataccggaaggaacccgcgctatgacggcaataaaaagacagaataaaacgc acgggtgttgggtcgtttgttcGAGTCATTTAAATACCGGTCTGGGCGAACAAACGATGCTCGCCTTCCAGAAAACCGAGGATGCGAACCACTTCATCCGGGGTCAGCACCACCGGCA AGCGCCGCGACGGCCGAGGTCTTCCGATCTCCTGAAGCCAGGGCAGATCCGTGC ACAGCACCTTGCCGTAGAAGAACAGCAAGGCCGCCAATGCCTGACGATGCGTGG AGACCGAAACCTTGCGCTCGTTCGCCAGCCAGGACAGAAATGCCTCGACTTCGC TGCTGCCCAAGGTTGCCGGGTGACGCACACCGTGGAAACGGATGAAGGCACGA ACCCAGTTGACATAAGCCTGTTCGGTTCGTAAACTGTAATGCAAGTAGCGTATGC GCTCACGCAACTGGTCCAGAACCTTGACCGAACGCAGCGGTGGTAACGGCGCAG TGGCGGTTTTCATGGCTTGTTATGACTGTTTTTTTGTACAGTCTATGCCTCGGGCAT CCAAGCAGCAAGCGCGTTACGCCGTGGGTCGATGTTTGATGTTATGGAGCAGCA ACGATGTTACGCAGCAGCAACGATGTTACGCAGCAGGGCAGTCGCCCTAAAACA AAGTTAGGTGGCTCAAGTATGGGCATCATTCGCACATGTAGGCTCGGCCCTGACC AAGTCAAATCCATGCGGGCTGCTCTTGATCTTTTCGGTCGTGAGTTCGGAGACGT AGCCACCTACTCCCAACATCAGCCGGACTCCGATTACCTCGGGAACTTGCTCCGT AGTAAGACATTCATCGCGCTTGCTGCCTTCGACCAAGAAGCGGTTGTTGGCGCTC TCGCGGCTTACGTTCTGCCCAAGTTTGAGCAGCCGCGTAGTGAGATCTATATCTAT GATCTCGCAGTCTCCGGCGAGCACCGGAGGCAGGGCATTGCCACCGCGCTCATC AATCTCCTCAAGCATGAGGCCAACGCGCTTGGTGCTTATGTGATCTACGTGCAAG CAGATTACGGTGACGATCCCGCAGTGGCTCTCTATACAAAGTTGGGCATACGGGA AGAAGTGATGCACTTTGATATCGACCCAAGTACCGCCACCTAACAATTCGTTCAA GCCGAGATCGGCTTCCCGGCCGCGGAGTTGTTCGGTAAATTGTCACAACGCCGC GAATATAGTCTTTACCATGCCCTTGGCCACGCCCCTCTTTAATACGACGGGCAATT TGCACTTCAGAAAATGAAGAGTTTGCTTTAGCCATAACAAAAGTCCAGTATGCTT TTTCACAGCATAACTGGACTGATTTCAGTTTACAACTATTCTGTCTAGTTTAAGAC TTTATTGTCATAGTTTAGATCTATTTTGTTCAGTTTAAGACTTTATTGTCCGCCCAC ACCCGCTTACGCAGGGCATCCATTTATTACTCAAatcggatcccgggcccgtcgactgcagaggcct gcatgcaagcttggcgtaatcatggtcatagctgtttcctgtgtgaaattgttatccgctcacaattccacacaacatacgagccggaag cataaagtgtaaagcctggggtgcctaatgagtgagctaactcacattaattgcgttgcgctcactgcccgctttccagtcgggaaacc tgtcgtgccagctgcattaatgaatcggccaacgcgcggggagaggcggtttgcgtattgggcgctcttccgcttcctcgctcactga ctcgctgcgctcggtcgttcggctgcggcgagcggtatcagctcactcaaaggcggtaatacggttatccacagaatcaggggataa cgcaggaaagaacatgtgagcaaaaggccagcaaaaggccaggaaccgtaaaaaggccgcgttgctggcgtttttccataggctc cgcccccctgacgagcatcacaaaaatcgacgctcaagtcagaggtggcgaaacccgacaggactataaagataccaggcgtttc cccctggaagctccctcgtgcgctctcctgttccgaccctgccgcttaccggatacctgtccgcctttctcccttcgggaagcgtggcg ctttctcatagctcacgctgtaggtatctcagttcggtgtaggtcgttcgctccaagctgggctgtgtgcacgaaccccccgttcagccc gaccgctgcgccttatccggtaactatcgtcttgagtccaacccggtaagacacgacttatcgccactggcagcagccactggtaaca ggattagcagagcgaggtatgtaggcggtgctacagagttcttgaagtggtggcctaactacggctacactagaagaacagtatttg gtatctgcgctctgctgaagccagttaccttcggaaaaagagttggtagctcttgatccggcaaacaaaccaccgctggtagcggtgg tttttttgtttgcaagcagcagattacgcgcagaaaaaaaggatctcaagaagatcctttgatcttttctacggggtctgacgctcagtgg aacgaaaactcacgttaagggattttggtcatgagattatcaaaaaggatcttcacctagatccttttaaattaaaaatgaagttttaaatc aatctaaagtatatatgagtaaacttggtctgacagttaccaatgcttaatcagtgaggcacctatctcagcgatctgtctatttcgttcatc catagttgcctgactccccgtcgtgtagataactacgatacgggagggcttaccatctggccccagtgctgcaatgataccgcgagac ccacgctcaccggctccagatttatcagcaataaaccagccagccggaagggccgagcgcagaagtggtcctgcaactttatccgc ctccatccagtctattaattgttgccgggaagctagagtaagtagttcgccagttaatagtttgcgcaacgttgttgccattgctacaggc atcgtggtgtcacgctcgtcgtttggtatggcttcattcagctccggttcccaacgatcaaggcgagttacatgatcccccatgttgtgca aaaaagcggttagctccttcggtcctccgatcgttgtcagaagtaagttggccgcagtgttatcactcatggttatggcagcactgcata attctcttactgtcatgccatccgtaagatgcttttctgtgactggtgagtactcaaccaagtcattctgagaatagtgtatgcggcgaccg agttgctcttgcccggcgtcaatacgggataataccgcgccacatagcagaactttaaaagtgctcatcattggaaaacgttcttcggg gcgaaaactctcaaggatcttaccgctgttgagatccagttcgatgtaacccactcgtgcacccaactgatcttcagcatcttttactttca ccagcgtttctgggtgagcaaaaacaggaaggcaaaatgccgcaaaaaagggaataagggcgacacggaaatgttgaatactcat actcttcctttttcaatattattgaagcatttatcagggttattgtctcatgagcggatacatatttgaatgtatttagaaaaataaacaaataggggttccgcgcacatttccccgaaaagtgccacctgacgtctaagaaaccattattatcatgacattaacctataaaaataggcgtatca cgaggccctttcgtc pFBacX-AAVRep2ACap5_37AE L21 (SEQ ID NO: 32) tcgcgcgtttcggtgatgacggtgaaaacctctgacacatgcagctcccggagacggtcacagcttgtctgtaagcggatgccggga gcagacaagcccgtcagggcgcgtcagcgggtgttggcgggtgtcggggctggcttaactatgcggcatcagagcagattgtact gagagtgcaccatatgcggtgtgaaataccgcacagatgcgtaaggagaaaataccgcatcaggcgccattcgccattcaggctgc gcaactgttgggaagggcgatcggtgcgggcctcttcgctattacgccagctggcgaaagggggatgtgctgcaaggcgattaagt tgggtaacgccagggttttcccagtcacgacgttgtaaaacgacggccagtgaattcgagctcggtacctcgcgaatgcatctagat GATTAAAAACATAACAGGAAGAAAAATGCCCCGCTGTGGGCGGACAAAATAGTT GGGAACTGGGAGGGGTGGAAATGGAGTTTTTAAGGATTATTTAGGGAAGAGTGA CAAAATAGATGGGAACTGGGTGTAGCGTCGTAAGCTAATACGAAAATTAAAAATG ACAAAATAGTTTGGAACTAGATTTCACTTATCTGGTTcggatctgggtccccctaggctcaagcagt gatcagatccagacatgataagatacattgatgagtttggacaaaccacaactagaatgcagtgaaaaaaatgctttatttgtgaaattt gtgatgctattgctttatttgtaaccattataagctgcaataaacaagttaacaacaacaattgcattcattttatgtttcaggttcaggggga ggtgtgggaggttttttaaagcaagtaaaacctctacaaatgtggtatggctgattatgatcctctagtacttctcgacaagcttgtcgag actgcaggctctagagtcgacctgcaggcatgcaagcttgattcctcgagtttattgttcaaagatgcagtcatccaaatccacattgac cagatcgcaggcagtgcaagcgtctggcacctttcccatgatatgatgaatgtagcacagtttctgatacgcctttttgacgacagaaa cgggllgagallclgacacgggaaagcaclclaaacaglclllclglccglgaglgaagcagalatllgaallclgallcaltclclcgcal tgtctgcagggaaacagcatcagattcatgcccacgtgacgagaacatttgttttggtacctgtctgcgtagttgatcgaagcttccgcg tctgacgtcgatggctgcgcaactgactcgcgcacccgtttgggctcacttatatctgcgtcactgggggcgggtcttttcttggctcca ccctttttgacgtagaattcatgctccacctcaaccacgtgatcctttgcccaccggaaaaagtctttgacttcctgcttggtgaccttccc aaagtcatgatccagacggcgggtgagttcaaatttgaacatccggtcttgcaacggctgctggtgttcgaaggtcgttgagttcccgt caatcacggcgcacatgttggtgttggaggtgacgatcacgggagtcgggtctatctgggccgaggacttgcatttctggtccacgc gcaccttgcttcctccgagaatggctttggccgactccacgaccttggcggtcatcttcccctcctcccaccagatcaccatcttgtcga cacagtcgttgaagggaaagttctcattggtccagtttacgcacccgtagaagggcacagtgtgggctatggcctccgcgatgttggt cttcccggtagttgcaggcccaaacagccagatggtgttcctcttgccgaactttttcgtggcccatcccagaaagacggaagccgca tattggggatcgtacccgtttagttccaaaattttataaatccgattgctggaaatgtcctccacgggctgctggcccaccaggtagtcg ggggcggttttagtcaggctcataatctttcccgcattgtccaaggcagccttgatttgggaccgcgagttggaggccgcattgaagg agatgtatgaAgcctggtcctcctggatccactgcttctccgaggtaatccccttgtccacgagccacccgaccagctccatgtacct ggctgaagtttttgatctgatcaccggcgcgtcagaattgggattctgattctctttgttctgctcctgcgtctgcgacacgtgcgtcagat gctgcgccaccaaccgtttacgctccgtgagattcaaacaggcgcttaaatactgttctaaattagtccacgcccactggagctcagg ctgggttttggggagcaagtaattggggatgtagcactcgtccaccaccttgttcccgcctccggcgccgtttctggtctttgtgaccgc gaaccagtttggcaaagtcggctcgatcccgcggtaaattctctgaatcagtttttcgcgaatctgactcaggaaacgtcccaaaacta aggatttcaccccggtggtttccacgagcacgtgtaagtggaagtagctctctcccttctcaaattgcacaaagaaaagggcctccgg ggccttactcacacggcgccactccgtcagaaagtcgcgctgcagcttctcggccacggtcaggggtgcctgctcaatcagattcag atccaagtcagaatctggcggcaactcccactccttctcggccacccagttcacaaagctgtcagaaatgccgggcagatgctcgtc aaggtcgctggggaccttaatcacaatctcgtaaaaccccgccagggcggcagatccgcgcccgatggtGCGGCCGCacg gtatgaataatccggaatatttataggtttttttattacaaaactgttacgaaaacagtaaaatacttatttatttgcgagatggttatcatttta attatctccatgatctattaatattcACGCGTcggagtatacggacctttaattcaacccaacacaatatattatagttaaataagaatt attatcaaatcatttgtatattaattaaaatactatactgtaaattacattttatttacaatcaatactagtaaaaggtaggttcaaccactgatg cctaggcacaccgaaacgactaaccctaattcttatcctttacttcaggcgcgcccggcttaagcgtacgAACTCCTAAAA AACCGCCACCgtTTTTatgtcttttgttgatcaccctccagattggttggaagaagttggtgaaggtcttcgcgagtttttgg gccttgaagcgggcccaccgaaaccaaaacccaatcagcagcatcaagatcaagcccgtggtcttgtgctgcctggttataactatct cggacccggaaacggtctcgatcgaggagagcctgtcaacagggcagacgaggtcgcgcgagagcacgacatctcgtacaacg agcagcttgaggcgggagacaacccctacctcaagtacaaccacgcggacgccgagtttcaggagaagctcgccgacgacacatccttcgggggaaacctcggaaaggcagtctttcaggccaagaaaagggttctcgaaccttttggcctggttgaagagggtgctaaga cggcccctaccggaaagcggatagacgaccactttccaaaaagaaagaaggctcggaccgaagaggactccaagccttccacctc gtcagacgccgaagctggacccagcggatcccagcagctgcaaatcccagcccaaccagcctcaagtttgggagctgatacaatg tctgcgggaggtggcggcccattgggcgacaataaccaaggtgccgatggagtgggcaatgcctcgggagattggcattgcgatt ccacgtggatgggggacagagtcgtcaccaagtccacccgaacctgggtgctgcccagctacaacaaccaccagtaccgagagat caaaagcggctccgtcgacggaagcaacgccaacgcctactttggatacagcaccccctgggggtactttgactttaaccgcttcca cagccactggagcccccgagactggcaaagactcatcaacaactactggggcttcagaccccggtccctcagagtcaaaatcttca acattcaagtcaaagaggtcacggtgcaggactccaccaccaccatcgccaacaacctcacctccaccgtccaagtgtttacggacg acgactaccagctgccctacgtcgtcggcaacgggaccgagggatgcctgccggccttccctccgcaggtctttacgctgccgcag tacggttacgcgacgctgaaccgcgacaacacagaaaatcccaccgagaggagcagcttcttctgcctagagtactttcccagcaa gatgctgagaacgggcaacaactttgagtttacctacaactttgaggaggtgcccttccactccagcttcgctcccagtcagaacctctt caagctggccaacccgctggtggaccagtacttgtaccgcttcgtgagcacaaataacactggcggagtccagttcaacaagaacct ggccgggagatacgccaacacctacaaaaactggttcccggggcccatgggccgaacccagggctggaacctgggctccgggg tcaaccgcgccagtgtcagcgccttcgccacgaccaataggatggagctcgagggcgcgagttaccaggtgcccccgcagccga acggcatgaccaacaacctccagggcagcaacacctatgccctggagaacactatgatcttcaacagccagccggcgaacccggg caccaccgccacgtacctcgagggcaacatgctcatcaccagcgagagcgagacgcagccggtgaaccgcgtggcgtacaacgt cggcgggcagatggccaccaacaaccagagctccaccactgcccccgcgaccggcacgtacaacctccaggaaatcgtgcccg gcagcgtgtggatggagagggacgtgtacctccaaggacccatctgggccaagatcccagagacgggggcgcactttcacccctc tccggccatgggcggattcggactcaaacacccaccgcccatgatgctcatcaagaacacgcctgtgcccggaaatatcaccagctt ctcggacgtgcccgtcagcagcttcatcacccagtacagcaccgggcaggtcaccgtggagatggagtgggagctcaagaagga aaactccaagaggtggaacccagagatccagtacacaaacaactacaacgacccccagtttgtggactttgccccggacagcaccg gggaatacagaaccaccagacctatcggaacccgataccttacccgacccctttaagctagcagctgatgcatagcatgcggtaccg ggagatgggggaggctaactgaaacacggaaggagacaataccggaaggaacccgcgctatgacggcaataaaaagacagaat aaaacgcacgggtgttgggtcgtttgttcGAGTCATTTAAATACCGGTCTGGGCGAACAAACGATG CTCGCCTTCCAGAAAACCGAGGATGCGAACCACTTCATCCGGGGTCAGCACCAC CGGCAAGCGCCGCGACGGCCGAGGTCTTCCGATCTCCTGAAGCCAGGGCAGATC CGTGCACAGCACCTTGCCGTAGAAGAACAGCAAGGCCGCCAATGCCTGACGATG CGTGGAGACCGAAACCTTGCGCTCGTTCGCCAGCCAGGACAGAAATGCCTCGAC TTCGCTGCTGCCCAAGGTTGCCGGGTGACGCACACCGTGGAAACGGATGAAGGC ACGAACCCAGTTGACATAAGCCTGTTCGGTTCGTAAACTGTAATGCAAGTAGCGTATGCGCTCACGCAACTGGTCCAGAACCTTGACCGAACGCAGCGGTGGTAACGGC GCAGTGGCGGTTTTCATGGCTTGTTATGACTGTTTTTTTGTACAGTCTATGCCTCG GGCATCCAAGCAGCAAGCGCGTTACGCCGTGGGTCGATGTTTGATGTTATGGAGC AGCAACGATGTTACGCAGCAGCAACGATGTTACGCAGCAGGGCAGTCGCCCTAA AACAAAGTTAGGTGGCTCAAGTATGGGCATCATTCGCACATGTAGGCTCGGCCCT GACCAAGTCAAATCCATGCGGGCTGCTCTTGATCTTTTCGGTCGTGAGTTCGGAG ACGTAGCCACCTACTCCCAACATCAGCCGGACTCCGATTACCTCGGGAACTTGCT CCGTAGTAAGACATTCATCGCGCTTGCTGCCTTCGACCAAGAAGCGGTTGTTGGC GCTCTCGCGGCTTACGTTCTGCCCAAGTTTGAGCAGCCGCGTAGTGAGATCTATAT CTATGATCTCGCAGTCTCCGGCGAGCACCGGAGGCAGGGCATTGCCACCGCGCT CATCAATCTCCTCAAGCATGAGGCCAACGCGCTTGGTGCTTATGTGATCTACGTGC AAGCAGATTACGGTGACGATCCCGCAGTGGCTCTCTATACAAAGTTGGGCATACG GGAAGAAGTGATGCACTTTGATATCGACCCAAGTACCGCCACCTAACAATTCGTT CAAGCCGAGATCGGCTTCCCGGCCGCGGAGTTGTTCGGTAAATTGTCACAACGC CGCGAATATAGTCTTTACCATGCCCTTGGCCACGCCCCTCTTTAATACGACGGGCA ACTTTTTTGTTCCAACCTATCGACGATAAAAACATTGGGAAACGTAGGATTTTTTGCCATGTTTTATGACCCAAATCATAACTATACATGATGCTTCACGATGTTTAATAG GACTTTATTGTCATAGTTTAGATCTATTTTGTTCAGTTTAAGACTTTATTGTCCGCC CACACCCGCTTACGCAGGGCATCCATTTATTACTCAAatcggatcccgggcccgtcgactgcagaggcctgcatgcaagcttggcgtaatcatggtcatagctgtttcctgtgtgaaattgttatccgctcacaattccacacaacatacgagccg gaagcataaagtgtaaagcctggggtgcctaatgagtgagctaactcacattaattgcgttgcgctcactgcccgctttccagtcggga aacctgtcgtgccagctgcattaatgaatcggccaacgcgcggggagaggcggtttgcgtattgggcgctcttccgcttcctcgctca ctgactcgctgcgctcggtcgttcggctgcggcgagcggtatcagctcactcaaaggcggtaatacggttatccacagaatcagggg ataacgcaggaaagaacatgtgagcaaaaggccagcaaaaggccaggaaccgtaaaaaggccgcgttgctggcgtttttccatag gctccgcccccctgacgagcatcacaaaaatcgacgctcaagtcagaggtggcgaaacccgacaggactataaagataccaggc gtttccccctggaagctccctcgtgcgctctcctgttccgaccctgccgcttaccggatacctgtccgcctttctcccttcgggaagcgt ggcgctttctcatagctcacgctgtaggtatctcagttcggtgtaggtcgttcgctccaagctgggctgtgtgcacgaaccccccgttca gcccgaccgctgcgccttatccggtaactatcgtcttgagtccaacccggtaagacacgacttatcgccactggcagcagccactgg taacaggattagcagagcgaggtatgtaggcggtgctacagagttcttgaagtggtggcctaactacggctacactagaagaacagt atttggtatctgcgctctgctgaagccagttaccttcggaaaaagagttggtagctcttgatccggcaaacaaaccaccgctggtagcg gtggtttttttgtttgcaagcagcagattacgcgcagaaaaaaaggatctcaagaagatcctttgatcttttctacggggtctgacgctca gtggaacgaaaactcacgttaagggattttggtcatgagattatcaaaaaggatcttcacctagatccttttaaattaaaaatgaagtttta aatcaatctaaagtatatatgagtaaacttggtctgacagttaccaatgcttaatcagtgaggcacctatctcagcgatctgtctatttcgtt catccatagttgcctgactccccgtcgtgtagataactacgatacgggagggcttaccatctggccccagtgctgcaatgataccgcg agacccacgctcaccggctccagatttatcagcaataaaccagccagccggaagggccgagcgcagaagtggtcctgcaactttat ccgcctccatccagtctattaattgttgccgggaagctagagtaagtagttcgccagttaatagtttgcgcaacgttgttgccattgctac aggcatcgtggtgtcacgctcgtcgtttggtatggcttcattcagctccggttcccaacgatcaaggcgagttacatgatcccccatgtt gtgcaaaaaagcggttagctccttcggtcctccgatcgttgtcagaagtaagttggccgcagtgttatcactcatggttatggcagcact gcataattctcttactgtcatgccatccgtaagatgcttttctgtgactggtgagtactcaaccaagtcattctgagaatagtgtatgcggc gaccgagttgctcttgcccggcgtcaatacgggataataccgcgccacatagcagaactttaaaagtgctcatcattggaaaacgttct tcggggcgaaaactctcaaggatcttaccgctgttgagatccagttcgatgtaacccactcgtgcacccaactgatcttcagcatctttt actttcaccagcgtttctgggtgagcaaaaacaggaaggcaaaatgccgcaaaaaagggaataagggcgacacggaaatgttgaat actcatactcttcctttttcaatattattgaagcatttatcagggttattgtctcatgagcggatacatatttgaatgtatttagaaaaataaaca aataggggttccgcgcacatttccccgaaaagtgccacctgacgtctaagaaaccattattatcatgacattaacctataaaaataggc gtatcacgaggccctttcgtc pFBacX-AAVRep2ACap5_37AE Syn21 (SEQ ID NO: 33) tcgcgcgtttcggtgatgacggtgaaaacctctgacacatgcagctcccggagacggtcacagcttgtctgtaagcggatgccggga gcagacaagcccgtcagggcgcgtcagcgggtgttggcgggtgtcggggctggcttaactatgcggcatcagagcagattgtact gagagtgcaccatatgcggtgtgaaataccgcacagatgcgtaaggagaaaataccgcatcaggcgccattcgccattcaggctgc gcaactgttgggaagggcgatcggtgcgggcctcttcgctattacgccagctggcgaaagggggatgtgctgcaaggcgattaagt tgggtaacgccagggttttcccagtcacgacgttgtaaaacgacggccagtgaattcgagctcggtacctcgcgaatgcatctagat GATTAAAAACATAACAGGAAGAAAAATGCCCCGCTGTGGGCGGACAAAATAGTT GGGAACTGGGAGGGGTGGAAATGGAGTTTTTAAGGATTATTTAGGGAAGAGTGA CAAAATAGATGGGAACTGGGTGTAGCGTCGTAAGCTAATACGAAAATTAAAAATG ACAAAATAGTTTGGAACTAGATTTCACTTATCTGGTTcggatctgggtccccctaggctcaagcagt gatcagatccagacatgataagatacattgatgagtttggacaaaccacaactagaatgcagtgaaaaaaatgctttatttgtgaaattt gtgatgctattgctttatttgtaaccattataagctgcaataaacaagttaacaacaacaattgcattcattttatgtttcaggttcaggggga ggtgtgggaggttttttaaagcaagtaaaacctctacaaatgtggtatggctgattatgatcctctagtacttctcgacaagcttgtcgag actgcaggctctagagtcgacctgcaggcatgcaagcttgattcctcgagtttattgttcaaagatgcagtcatccaaatccacattgac cagatcgcaggcagtgcaagcgtctggcacctttcccatgatatgatgaatgtagcacagtttctgatacgcctttttgacgacagaaa cgggttgagattctgacacgggaaagcactctaaacagtctttctgtccgtgagtgaagcagatatttgaattctgattcattctctcgcat tgtctgcagggaaacagcatcagattcatgcccacgtgacgagaacatttgttttggtacctgtctgcgtagttgatcgaagcttccgcg tctgacgtcgatggctgcgcaactgactcgcgcacccgtttgggctcacttatatctgcgtcactgggggcgggtcttttcttggctcca ccctttttgacgtagaattcatgctccacctcaaccacgtgatcctttgcccaccggaaaaagtctttgacttcctgcttggtgaccttccc aaagtcatgatccagacggcgggtgagttcaaatttgaacatccggtcttgcaacggctgctggtgttcgaaggtcgttgagttcccgt caatcacggcgcacatgttggtgttggaggtgacgatcacgggagtcgggtctatctgggccgaggacttgcatttctggtccacgcgcaccttgcttcctccgagaatggctttggccgactccacgaccttggcggtcatcttcccctcctcccaccagatcaccatcttgtcga cacagtcgttgaagggaaagttctcattggtccagtttacgcacccgtagaagggcacagtgtgggctatggcctccgcgatgttggt cttcccggtagttgcaggcccaaacagccagatggtgttcctcttgccgaactttttcgtggcccatcccagaaagacggaagccgca tattggggatcgtacccgtttagttccaaaattttataaatccgattgctggaaatgtcctccacgggctgctggcccaccaggtagtcg ggggcggttttagtcaggctcataatctttcccgcattgtccaaggcagccttgatttgggaccgcgagttggaggccgcattgaagg agatgtatgaAgcctggtcctcctggatccactgcttctccgaggtaatccccttgtccacgagccacccgaccagctccatgtacct ggctgaagtttttgatctgatcaccggcgcgtcagaattgggattctgattctctttgttctgctcctgcgtctgcgacacgtgcgtcagat gctgcgccaccaaccgtttacgctccgtgagattcaaacaggcgcttaaatactgttctaaattagtccacgcccactggagctcagg ctgggttttggggagcaagtaattggggatgtagcactcgtccaccaccttgttcccgcctccggcgccgtttctggtctttgtgaccgc gaaccagtttggcaaagtcggctcgatcccgcggtaaattctctgaatcagtttttcgcgaatctgactcaggaaacgtcccaaaacta aggatttcaccccggtggtttccacgagcacgtgtaagtggaagtagctctctcccttctcaaattgcacaaagaaaagggcctccgg ggccttactcacacggcgccactccgtcagaaagtcgcgctgcagcttctcggccacggtcaggggtgcctgctcaatcagattcag atccaagtcagaatctggcggcaactcccactccttctcggccacccagttcacaaagctgtcagaaatgccgggcagatgctcgtc aaggtcgctggggaccttaatcacaatctcgtaaaaccccgccagggcggcagatccgcgcccgatggtGCGGCCGCacg gtatgaataatccggaatatttataggtttttttattacaaaactgttacgaaaacagtaaaatacttatttatttgcgagatggttatcatttta attatctccatgatctattaatattcACGCGTcggagtatacggacctttaattcaacccaacacaatatattatagttaaataagaatt attatcaaatcatttgtatattaattaaaatactatactgtaaattacattttatttacaatcaatactagtaaaaggtaggttcaaccactgatg cctaggcacaccgaaacgactaaccctaattcttatcctttacttcaggcgcgcccggcttaagcgtacgaacttaaaaaaaaaaatca aagtTTTTatgtcttttgttgatcaccctccagattggttggaagaagttggtgaaggtcttcgcgagtttttgggccttgaagcgggc ccaccgaaaccaaaacccaatcagcagcatcaagatcaagcccgtggtcttgtgctgcctggttataactatctcggacccggaaac ggtctcgatcgaggagagcctgtcaacagggcagacgaggtcgcgcgagagcacgacatctcgtacaacgagcagcttgaggcg ggagacaacccctacctcaagtacaaccacgcggacgccgagtttcaggagaagctcgccgacgacacatccttcgggggaaac ctcggaaaggcagtctttcaggccaagaaaagggttctcgaaccttttggcctggttgaagagggtgctaagacggcccctaccgga aagcggatagacgaccactttccaaaaagaaagaaggctcggaccgaagaggactccaagccttccacctcgtcagacgccgaa gctggacccagcggatcccagcagctgcaaatcccagcccaaccagcctcaagtttgggagctgatacaatgtctgcgggaggtg gcggcccattgggcgacaataaccaaggtgccgatggagtgggcaatgcctcgggagattggcattgcgattccacgtggatggg ggacagagtcgtcaccaagtccacccgaacctgggtgctgcccagctacaacaaccaccagtaccgagagatcaaaagcggctcc gtcgacggaagcaacgccaacgcctactttggatacagcaccccctgggggtactttgactttaaccgcttccacagccactggagc ccccgagactggcaaagactcatcaacaactactggggcttcagaccccggtccctcagagtcaaaatcttcaacattcaagtcaaa gaggtcacggtgcaggactccaccaccaccatcgccaacaacctcacctccaccgtccaagtgtttacggacgacgactaccagct gccctacgtcgtcggcaacgggaccgagggatgcctgccggccttccctccgcaggtctttacgctgccgcagtacggttacgcga cgctgaaccgcgacaacacagaaaatcccaccgagaggagcagcttcttctgcctagagtactttcccagcaagatgctgagaacg ggcaacaactttgagtttacctacaactttgaggaggtgcccttccactccagcttcgctcccagtcagaacctcttcaagctggccaa cccgctggtggaccagtacttgtaccgcttcgtgagcacaaataacactggcggagtccagttcaacaagaacctggccgggagat acgccaacacctacaaaaactggttcccggggcccatgggccgaacccagggctggaacctgggctccggggtcaaccgcgcca gtgtcagcgccttcgccacgaccaataggatggagctcgagggcgcgagttaccaggtgcccccgcagccgaacggcatgacca acaacctccagggcagcaacacctatgccctggagaacactatgatcttcaacagccagccggcgaacccgggcaccaccgcca cgtacctcgagggcaacatgctcatcaccagcgagagcgagacgcagccggtgaaccgcgtggcgtacaacgtcggcgggcag atggccaccaacaaccagagctccaccactgcccccgcgaccggcacgtacaacctccaggaaatcgtgcccggcagcgtgtgg atggagagggacgtgtacctccaaggacccatctgggccaagatcccagagacgggggcgcactttcacccctctccggccatgg gcggattcggactcaaacacccaccgcccatgatgctcatcaagaacacgcctgtgcccggaaatatcaccagcttctcggacgtgc ccgtcagcagcttcatcacccagtacagcaccgggcaggtcaccgtggagatggagtgggagctcaagaaggaaaactccaaga ggtggaacccagagatccagtacacaaacaactacaacgacccccagtttgtggactttgccccggacagcaccggggaatacag aaccaccagacctatcggaacccgataccttacccgacccctttaagctagcagctgatgcatagcatgcggtaccgggagatggg ggaggctaactgaaacacggaaggagacaataccggaaggaacccgcgctatgacggcaataaaaagacagaataaaacgcac gggtgttgggtcgtttgttcGAGTCATTTAAATACCGGTCTGGGCGAACAAACGATGCTCGCC TTCCAGAAAACCGAGGATGCGAACCACTTCATCCGGGGTCAGCACCACCGGCAA GCGCCGCGACGGCCGAGGTCTTCCGATCTCCTGAAGCCAGGGCAGATCCGTGCACAGCACCTTGCCGTAGAAGAACAGCAAGGCCGCCAATGCCTGACGATGCGTGGAGACCGAAACCTTGCGCTCGTTCGCCAGCCAGGACAGAAATGCCTCGACTTCGCT GCTGCCCAAGGTTGCCGGGTGACGCACACCGTGGAAACGGATGAAGGCACGAA CCCAGTTGACATAAGCCTGTTCGGTTCGTAAACTGTAATGCAAGTAGCGTATGCG CTCACGCAACTGGTCCAGAACCTTGACCGAACGCAGCGGTGGTAACGGCGCAGT GGCGGTTTTCATGGCTTGTTATGACTGTTTTTTTGTACAGTCTATGCCTCGGGCAT CCAAGCAGCAAGCGCGTTACGCCGTGGGTCGATGTTTGATGTTATGGAGCAGCA ACGATGTTACGCAGCAGCAACGATGTTACGCAGCAGGGCAGTCGCCCTAAAACA AAGTTAGGTGGCTCAAGTATGGGCATCATTCGCACATGTAGGCTCGGCCCTGACC AAGTCAAATCCATGCGGGCTGCTCTTGATCTTTTCGGTCGTGAGTTCGGAGACGT AGCCACCTACTCCCAACATCAGCCGGACTCCGATTACCTCGGGAACTTGCTCCGT AGTAAGACATTCATCGCGCTTGCTGCCTTCGACCAAGAAGCGGTTGTTGGCGCTC TCGCGGCTTACGTTCTGCCCAAGTTTGAGCAGCCGCGTAGTGAGATCTATATCTAT GATCTCGCAGTCTCCGGCGAGCACCGGAGGCAGGGCATTGCCACCGCGCTCATC AATCTCCTCAAGCATGAGGCCAACGCGCTTGGTGCTTATGTGATCTACGTGCAAG CAGATTACGGTGACGATCCCGCAGTGGCTCTCTATACAAAGTTGGGCATACGGGA AGAAGTGATGCACTTTGATATCGACCCAAGTACCGCCACCTAACAATTCGTTCAA GCCGAGATCGGCTTCCCGGCCGCGGAGTTGTTCGGTAAATTGTCACAACGCCGC GAATATAGTCTTTACCATGCCCTTGGCCACGCCCCTCTTTAATACGACGGGCAATT TGCACTTCAGAAAATGAAGAGTTTGCTTTAGCCATAACAAAAGTCCAGTATGCTT TTTCACAGCATAACTGGACTGATTTCAGTTTACAACTATTCTGTCTAGTTTAAGAC TTTATTGTCATAGTTTAGATCTATTTTGTTCAGTTTAAGACTTTATTGTCCGCCCAC ACCCGCTTACGCAGGGCATCCATTTATTACTCAAatcggatcccgggcccgtcgactgcagaggcct gcatgcaagcttggcgtaatcatggtcatagctgtttcctgtgtgaaattgttatccgctcacaattccacacaacatacgagccggaag cataaagtgtaaagcctggggtgcctaatgagtgagctaactcacattaattgcgttgcgctcactgcccgctttccagtcgggaaacc tgtcgtgccagctgcattaatgaatcggccaacgcgcggggagaggcggtttgcgtattgggcgctcttccgcttcctcgctcactga ctcgctgcgctcggtcgttcggctgcggcgagcggtatcagctcactcaaaggcggtaatacggttatccacagaatcaggggataa cgcaggaaagaacatgtgagcaaaaggccagcaaaaggccaggaaccgtaaaaaggccgcgttgctggcgtttttccataggctc cgcccccctgacgagcatcacaaaaatcgacgctcaagtcagaggtggcgaaacccgacaggactataaagataccaggcgtttc cccctggaagctccctcgtgcgctctcctgttccgaccctgccgcttaccggatacctgtccgcclttctcccttcgggaagcgtggcg ctttctcatagctcacgctgtaggtatctcagttcggtgtaggtcgttcgctccaagctgggctgtgtgcacgaaccccccgttcagccc gaccgctgcgccttatccggtaactatcgtcttgagtccaacccggtaagacacgacttatcgccactggcagcagccactggtaaca ggattagcagagcgaggtatgtaggcggtgctacagagttcttgaagtggtggcctaactacggctacactagaagaacagtatttg gtatctgcgctctgctgaagccagttaccttcggaaaaagagttggtagctcttgatccggcaaacaaaccaccgctggtagcggtgg tttttttgtttgcaagcagcagattacgcgcagaaaaaaaggatctcaagaagatcctttgatcttttctacggggtctgacgctcagtgg aacgaaaactcacgttaagggattttggtcatgagattatcaaaaaggatcttcacctagatccttttaaattaaaaatgaagttttaaatc aatctaaagtatatatgagtaaacttggtctgacagttaccaatgcttaatcagtgaggcacctatctcagcgatctgtctatttcgttcatc catagttgcctgactccccgtcgtgtagataactacgatacgggagggcttaccatctggccccagtgctgcaatgataccgcgagac ccacgctcaccggctccagatttatcagcaataaaccagccagccggaagggccgagcgcagaagtggtcctgcaactttatccgc ctccatccagtctattaattgttgccgggaagctagagtaagtagttcgccagttaatagtttgcgcaacgttgttgccattgctacaggc atcgtggtgtcacgctcgtcgtttggtatggcttcattcagctccggttcccaacgatcaaggcgagttacatgatcccccatgttgtgca aaaaagcggttagctccttcggtcctccgatcgttgtcagaagtaagttggccgcagtgttatcactcatggttatggcagcactgcata attctcttactgtcatgccatccgtaagatgcttttctgtgactggtgagtactcaaccaagtcattctgagaatagtgtatgcggcgaccg agttgctcttgcccggcgtcaatacgggataataccgcgccacatagcagaactttaaaagtgctcatcattggaaaacgttcttcggg gcgaaaactctcaaggatcttaccgctgttgagatccagttcgatgtaacccactcgtgcacccaactgatcttcagcatcttttactttca ccagcgtttctgggtgagcaaaaacaggaaggcaaaatgccgcaaaaaagggaataagggcgacacggaaatgttgaatactcat actcttcctttttcaatattattgaagcatttatcagggttattgtctcatgagcggatacatatttgaatgtatttagaaaaataaacaaatag gggttccgcgcacatttccccgaaaagtgccacctgacgtctaagaaaccattattatcatgacattaacctataaaaataggcgtatca cgaggccctttcgtcpFBacX-AAVRep2ACap5_40AE AcNPV (SEQ ID NO: 34) tcgcgcgtttcggtgatgacggtgaaaacctctgacacatgcagctcccggagacggtcacagcttgtctgtaagcggatgccggga gcagacaagcccgtcagggcgcgtcagcgggtgttggcgggtgtcggggctggcttaactatgcggcatcagagcagattgtact gagagtgcaccatatgcggtgtgaaataccgcacagatgcgtaaggagaaaataccgcatcaggcgccattcgccattcaggctgc gcaactgttgggaagggcgatcggtgcgggcctcttcgctattacgccagctggcgaaagggggatgtgctgcaaggcgattaagt tgggtaacgccagggttttcccagtcacgacgttgtaaaacgacggccagtgaattcgagctcggtacctcgcgaatgcatctagat GATTAAAAACATAACAGGAAGAAAAATGCCCCGCTGTGGGCGGACAAAATAGTT GGGAACTGGGAGGGGTGGAAATGGAGTTTTTAAGGATTATTTAGGGAAGAGTGA CAAAATAGATGGGAACTGGGTGTAGCGTCGTAAGCTAATACGAAAATTAAAAATG ACAAAATAGTTTGGAACTAGATTTCACTTATCTGGTTcggatctgggtccccctaggctcaagcagt gatcagatccagacatgataagatacattgatgagtttggacaaaccacaactagaatgcagtgaaaaaaatgctttatttgtgaaattt gtgatgctattgctttatttgtaaccattataagctgcaataaacaagttaacaacaacaattgcattcattttatgtttcaggttcaggggga ggtgtgggaggttttttaaagcaagtaaaacctctacaaatgtggtatggctgattatgatcctctagtacttctcgacaagcttgtcgag actgcaggctctagagtcgacctgcaggcatgcaagcttgattcctcgagtttattgttcaaagatgcagtcatccaaatccacattgac cagatcgcaggcagtgcaagcgtctggcacctttcccatgatatgatgaatgtagcacagtttctgatacgcctttttgacgacagaaa cgggttgagattctgacacgggaaagcactctaaacagtctttctgtccgtgagtgaagcagatatttgaattctgattcattctctcgcat tgtctgcagggaaacagcatcagattcatgcccacgtgacgagaacatttgttttggtacctgtctgcgtagttgatcgaagcttccgcg tctgacgtcgatggctgcgcaactgactcgcgcacccgtttgggctcacttatatctgcgtcactgggggcgggtcttttcttggctcca ccctttttgacgtagaattcatgctccacctcaaccacgtgatcctttgcccaccggaaaaagtctttgacttcctgcttggtgaccttccc aaagtcatgatccagacggcgggtgagttcaaatttgaacatccggtcttgcaacggctgctggtgttcgaaggtcgttgagttcccgt caatcacggcgcacatgttggtgttggaggtgacgatcacgggagtcgggtctatctgggccgaggacttgcatttctggtccacgc gcaccttgcttcctccgagaatggctttggccgactccacgaccttggcggtcatcttcccctcctcccaccagatcaccatcttgtcga cacagtcgttgaagggaaagttctcattggtccagtttacgcacccgtagaagggcacagtgtgggctatggcctccgcgatgttggt cttcccggtagttgcaggcccaaacagccagatggtgttcctcttgccgaactttttcgtggcccatcccagaaagacggaagccgca tattggggatcgtacccgtttagttccaaaattttataaatccgattgctggaaatgtcctccacgggctgctggcccaccaggtagtcg ggggcggttttagtcaggctcataatctttcccgcattgtccaaggcagccttgatttgggaccgcgagttggaggccgcattgaagg agatgtatgaAgcctggtcctcctggatccactgcttctccgaggtaatccccttgtccacgagccacccgaccagctccatgtacct ggctgaagtttttgatctgatcaccggcgcgtcagaattgggattctgattctctttgttctgctcctgcgtctgcgacacgtgcgtcagat gctgcgccaccaaccgtttacgctccgtgagattcaaacaggcgcttaaatactgttctaaattagtccacgcccactggagctcagg ctgggttttggggagcaagtaattggggatgtagcactcgtccaccaccttgttcccgcctccggcgccgtttctggtctttgtgaccgc gaaccagtttggcaaagtcggctcgatcccgcggtaaattctctgaatcagtttttcgcgaatctgactcaggaaacgtcccaaaacta aggatttcaccccggtggtttccacgagcacgtgtaagtggaagtagctctctcccttctcaaattgcacaaagaaaagggcctccgg ggccttactcacacggcgccactccgtcagaaagtcgcgctgcagcttclcggccacggtcaggggtgcctgctcaatcagattcag atccaagtcagaatctggcggcaactcccactccttctcggccacccagttcacaaagctgtcagaaatgccgggcagatgctcgtc aaggtcgctggggaccttaatcacaatctcgtaaaaccccgccagggcggcagatccgcgcccgatggtGCGGCCGCacg gtatgaataatccggaatatttataggtttttttattacaaaactgttacgaaaacagtaaaatacttatttatttgcgagatggttatcatttta attatctccatgatctattaatattcACGCGTcggagtatacggacctttaattcaacccaacacaatatattatagttaaataagaatt attatcaaatcatttgtatattaattaaaatactatactgtaaattacattttatttacaatcaatactagtaaaaggtaggttcaaccactgatg cctaggcacaccgaaacgactaaccctaattcttatcctttacttcaggcgcgcccggcttaagcgtacgAATTACAAATTATATAACAAATATTTTatgtcttttgttgatcaccctccagattggttggaagaagttggtgaaggtcttcgcgagtttttgggc cttgaagcgggcccaccgaaaccaaaacccaatcagcagcatcaagatcaagcccgtggtcttgtgctgcctggttataactatctcg gacccggaaacggtctcgatcgaggagagcctgtcaacagggcagacgaggtcgcgcgagagcacgacatctcgtacaacgag cagcttgaggcgggagacaacccctacctcaagtacaaccacgcggacgccgagtttcaggagaagctcgccgacgacacatcct tcgggggaaacctcggaaaggcagtctttcaggccaagaaaagggttctcgaaccttttggcctggttgaagagggtgctaagacg gcccctaccggaaagcggatagacgaccactttccaaaaagaaagaaggctcggaccgaagaggactccaagccttccacctcgt cagacgccgaagctggacccagcggatcccagcagctgcaaatcccagcccaaccagcctcaagtttgggagctgatacaatgtctgcgggaggtggcggcccattgggcgacaataaccaaggtgccgatggagtgggcaatgcctcgggagattggcattgcgattcca cgtggatgggggacagagtcgtcaccaagtccacccgaacctgggtgctgcccagctacaacaaccaccagtaccgagagatcaa aagcggctccgtcgacggaagcaacgccaacgcctactttggatacagcaccccctgggggtactttgactttaaccgcttccacag ccactggagcccccgagactggcaaagactcatcaacaactactggggcttcagaccccggtccctcagagtcaaaatcttcaacat tcaagtcaaagaggtcacggtgcaggactccaccaccaccatcgccaacaacctcacctccaccgtccaagtgtttacggacgacg actaccagctgccctacgtcgtcggcaacgggaccgagggatgcctgccggccttccctccgcaggtctttacgctgccgcagtac ggttacgcgacgctgaaccgcgacaacacagaaaatcccaccgagaggagcagcttcttctgcctagagtactttcccagcaagat gctgagaacgggcaacaactttgagtttacctacaactttgaggaggtgcccttccactccagcttcgctcccagtcagaacctcttca agctggccaacccgctggtggaccagtacttgtaccgcttcgtgagcacaaataacactggcggagtccagttcaacaagaacctg gccgggagatacgccaacacctacaaaaactggttcccggggcccatgggccgaacccagggctggaacctgggctccggggtc aaccgcgccagtgtcagcgccttcgccacgaccaataggatggagctcgagggcgcgagttaccaggtgcccccgcagccgaac ggcatgaccaacaacctccagggcagcaacacctatgccctggagaacactatgatcttcaacagccagccggcgaacccgggca ccaccgccacgtacctcgagggcaacatgctcatcaccagcgagagcgagacgcagccggtgaaccgcgtggcgtacaacgtcg gcgggcagatggccaccaacaaccagagctccaccactgcccccgcgaccggcacgtacaacctccaggaaatcgtgcccggc agcgtgtggatggagagggacgtgtacctccaaggacccatctgggccaagatcccagagacgggggcgcactttcacccctctc cggccatgggcggattcggactcaaacacccaccgcccatgatgctcatcaagaacacgcctgtgcccggaaatatcaccagcttct cggacgtgcccgtcagcagcttcatcacccagtacagcaccgggcaggtcaccgtggagatggagtgggagctcaagaaggaaa actccaagaggtggaacccagagatccagtacacaaacaactacaacgacccccagtttgtggactttgccccggacagcaccgg ggaatacagaaccaccagacctatcggaacccgataccttacccgacccctttaagctagcagctgatgcatagcatgcggtaccgg gagatgggggaggctaactgaaacacggaaggagacaataccggaaggaacccgcgctatgacggcaataaaaagacagaata aaacgcacgggtgttgggtcgtttgttcGAGTCATTTAAATACCGGTCTGGGCGAACAAACGATGC TCGCCTTCCAGAAAACCGAGGATGCGAACCACTTCATCCGGGGTCAGCACCACC GGCAAGCGCCGCGACGGCCGAGGTCTTCCGATCTCCTGAAGCCAGGGCAGATCC GTGCACAGCACCTTGCCGTAGAAGAACAGCAAGGCCGCCAATGCCTGACGATGC GTGGAGACCGAAACCTTGCGCTCGTTCGCCAGCCAGGACAGAAATGCCTCGACT TCGCTGCTGCCCAAGGTTGCCGGGTGACGCACACCGTGGAAACGGATGAAGGCA CGAACCCAGTTGACATAAGCCTGTTCGGTTCGTAAACTGTAATGCAAGTAGCGTATGCGCTCACGCAACTGGTCCAGAACCTTGACCGAACGCAGCGGTGGTAACGGCG CAGTGGCGGTTTTCATGGCTTGTTATGACTGTTTTTTTGTACAGTCTATGCCTCGG GCATCCAAGCAGCAAGCGCGTTACGCCGTGGGTCGATGTTTGATGTTATGGAGCA GCAACGATGTTACGCAGCAGCAACGATGTTACGCAGCAGGGCAGTCGCCCTAAA ACAAAGTTAGGTGGCTCAAGTATGGGCATCATTCGCACATGTAGGCTCGGCCCTG ACCAAGTCAAATCCATGCGGGCTGCTCTTGATCTTTTCGGTCGTGAGTTCGGAGA CGTAGCCACCTACTCCCAACATCAGCCGGACTCCGATTACCTCGGGAACTTGCTC CGTAGTAAGACATTCATCGCGCTTGCTGCCTTCGACCAAGAAGCGGTTGTTGGCG CTCTCGCGGCTTACGTTCTGCCCAAGTTTGAGCAGCCGCGTAGTGAGATCTATATC TATGATCTCGCAGTCTCCGGCGAGCACCGGAGGCAGGGCATTGCCACCGCGCTC ATCAATCTCCTCAAGCATGAGGCCAACGCGCTTGGTGCTTATGTGATCTACGTGC AAGCAGATTACGGTGACGATCCCGCAGTGGCTCTCTATACAAAGTTGGGCATACG GGAAGAAGTGATGCACTTTGATATCGACCCAAGTACCGCCACCTAACAATTCGTT CAAGCCGAGATCGGCTTCCCGGCCGCGGAGTTGTTCGGTAAATTGTCACAACGC CGCGAATATAGTCTTTACCATGCCCTTGGCCACGCCCCTCTTTAATACGACGGGCA ACT TT TT TG TTC CA AC CT ATC GA CG ATA AA AA CA TT GG GA AA CG TA GG AT TT TT TG CC AT GT TT TA TG AC CC AA AT CA TA AC TA TA CA TGA TG CT TC AC GA TG TT TA AT AG GACTTTATTGTCATAGTTTAGATCTATTTTGTTCAGTTTAAGACTTTATTGTCCGCCCACACCCGCTTACGCAGGGCATCCATTTATTACTCAAatcggatcccgggcccgtcgactgcagag gcctgcatgcaagcttggcgtaatcatggtcatagctgtttcctgtgtgaaattgttatccgctcacaattccacacaacatacgagccg gaagcataaagtgtaaagcctggggtgcctaatgagtgagctaactcacattaattgcgttgcgctcactgcccgctttccagtcggga aacctgtcgtgccagctgcattaatgaatcggccaacgcgcggggagaggcggtttgcgtattgggcgctcttccgcttcctcgctcactgactcgctgcgctcggtcgttcggctgcggcgagcggtatcagctcactcaaaggcggtaatacggttatccacagaatcagggg ataacgcaggaaagaacatgtgagcaaaaggccagcaaaaggccaggaaccgtaaaaaggccgcgttgctggcgtttttccatag gctccgcccccctgacgagcatcacaaaaatcgacgctcaagtcagaggtggcgaaacccgacaggactataaagataccaggc gtttccccctggaagctccctcgtgcgctctcctgttccgaccctgccgcttaccggatacctgtccgcctttctcccttcgggaagcgt ggcgctttctcatagctcacgctgtaggtatctcagttcggtgtaggtcgttcgctccaagctgggctgtgtgcacgaaccccccgttca gcccgaccgctgcgccttatccggtaactatcgtcttgagtccaacccggtaagacacgacttatcgccactggcagcagccactgg taacaggattagcagagcgaggtatgtaggcggtgctacagagttcttgaagtggtggcctaactacggctacactagaagaacagt atttggtatctgcgctctgctgaagccagttaccttcggaaaaagagttggtagctcttgatccggcaaacaaaccaccgctggtagcg gtggtttttttgtttgcaagcagcagattacgcgcagaaaaaaaggatctcaagaagatcctttgatcttttctacggggtctgacgctca gtggaacgaaaactcacgttaagggattttggtcatgagattatcaaaaaggatcttcacctagatccttttaaattaaaaatgaagtttta aatcaatctaaagtatatatgagtaaacttggtctgacagttaccaatgcttaatcagtgaggcacctatctcagcgatctgtctatttcgtt catccatagttgcctgactccccgtcgtgtagataactacgatacgggagggcttaccatctggccccagtgctgcaatgataccgcg agacccacgctcaccggctccagatttatcagcaataaaccagccagccggaagggccgagcgcagaagtggtcctgcaactttat ccgcctccatccagtctattaattgttgccgggaagctagagtaagtagttcgccagttaatagtttgcgcaacgttgttgccattgctac aggcatcgtggtgtcacgctcgtcgtttggtatggcttcattcagctccggttcccaacgatcaaggcgagttacatgatcccccatgtt gtgcaaaaaagcggttagctccttcggtcctccgatcgttgtcagaagtaagttggccgcagtgttatcactcatggttatggcagcact gcataattctcttactgtcatgccatccgtaagatgcttttctgtgactggtgagtactcaaccaagtcattctgagaatagtgtatgcggc gaccgagttgctcttgcccggcgtcaatacgggataataccgcgccacatagcagaactttaaaagtgctcatcattggaaaacgttct tcggggcgaaaactctcaaggatcttaccgctgttgagatccagttcgatgtaacccactcgtgcacccaactgatcttcagcatctttt actttcaccagcgtttctgggtgagcaaaaacaggaaggcaaaatgccgcaaaaaagggaataagggcgacacggaaatgttgaat actcatactcttcctttttcaatattattgaagcatttatcagggttattgtctcatgagcggatacatatttgaatgtatttagaaaaataaaca aataggggttccgcgcacatttccccgaaaagtgccacctgacgtctaagaaaccattattatcatgacattaacctataaaaataggc gtatcacgaggccctttcgtc pFBacX-AAVRep2ACap5_40AE EoNPV (SEQ ID NO: 35) tcgcgcgtttcggtgatgacggtgaaaacctctgacacatgcagctcccggagacggtcacagcttgtctgtaagcggatgccggga gcagacaagcccgtcagggcgcgtcagcgggtgttggcgggtgtcggggctggcttaactatgcggcatcagagcagattgtact gagagtgcaccatatgcggtgtgaaataccgcacagatgcgtaaggagaaaataccgcatcaggcgccattcgccattcaggctgc gcaactgttgggaagggcgatcggtgcgggcctcttcgctattacgccagctggcgaaagggggatgtgctgcaaggcgattaagt tgggtaacgccagggttttcccagtcacgacgttgtaaaacgacggccagtgaattcgagctcggtacctcgcgaatgcatctagat GATTAAAAACATAACAGGAAGAAAAATGCCCCGCTGTGGGCGGACAAAATAGTT GGGAACTGGGAGGGGTGGAAATGGAGTTTTTAAGGATTATTTAGGGAAGAGTGA CAAAATAGATGGGAACTGGGTGTAGCGTCGTAAGCTAATACGAAAATTAAAAATG ACAAAATAGTTTGGAACTAGATTTCACTTATCTGGTTcggatctgggtccccctaggctcaagcagt gatcagatccagacatgataagatacattgatgagtttggacaaaccacaactagaatgcagtgaaaaaaatgctttatttgtgaaattt gtgatgctattgctttatttgtaaccattataagctgcaataaacaagttaacaacaacaattgcattcattttatgtttcaggttcaggggga ggtgtgggaggttttttaaagcaagtaaaacctctacaaatgtggtatggctgattatgatcctctagtacttctcgacaagcttgtcgag actgcaggctctagagtcgacctgcaggcatgcaagcttgattcctcgagtttattgttcaaagatgcagtcatccaaatccacattgac cagatcgcaggcagtgcaagcgtctggcacctttcccatgatatgatgaatgtagcacagtttctgatacgcctttttgacgacagaaa cgggttgagattctgacacgggaaagcactctaaacagtctttctgtccgtgagtgaagcagatatttgaattctgattcattctctcgcat tgtctgcagggaaacagcatcagattcatgcccacgtgacgagaacatttgttttggtacctgtctgcgtagttgatcgaagcttccgcg tctgacgtcgatggctgcgcaactgactcgcgcacccgtttgggctcacttatatctgcgtcactgggggcgggtcttttcttggctcca ccctttttgacgtagaattcatgctccacctcaaccacgtgatcctttgcccaccggaaaaagtctttgacttcctgcttggtgaccttccc aaagtcatgatccagacggcgggtgagttcaaatttgaacatccggtcttgcaacggctgctggtgttcgaaggtcgttgagttcccgt caatcacggcgcacatgttggtgttggaggtgacgatcacgggagtcgggtctatctgggccgaggacttgcatttctggtccacgc gcaccttgcttcctccgagaatggctttggccgactccacgaccttggcggtcatcttcccctcctcccaccagatcaccatcttgtcgacacagtcgttgaagggaaagttctcattggtccagtttacgcacccgtagaagggcacagtgtgggctatggcctccgcgatgttggt cttcccggtagttgcaggcccaaacagccagatggtgttcctcttgccgaactttttcgtggcccatcccagaaagacggaagccgca tattggggatcgtacccgtttagttccaaaattttataaatccgattgctggaaatgtcctccacgggctgctggcccaccaggtagtcg ggggcggttttagtcaggctcataatctttcccgcattgtccaaggcagccttgatttgggaccgcgagttggaggccgcattgaagg agatgtatgaAgcctggtcctcctggatccactgcttctccgaggtaatccccttgtccacgagccacccgaccagctccatgtacct ggctgaagtttttgatctgatcaccggcgcgtcagaattgggattctgattctctttgttctgctcctgcgtctgcgacacgtgcgtcagat gctgcgccaccaaccgtttacgctccgtgagattcaaacaggcgcttaaatactgttctaaattagtccacgcccactggagctcagg ctgggttttggggagcaagtaattggggatgtagcactcgtccaccaccttgttcccgcctccggcgccgtttctggtctttgtgaccgc gaaccagtttggcaaagtcggctcgatcccgcggtaaattctctgaatcagtttttcgcgaatctgactcaggaaacgtcccaaaacta aggatttcaccccggtggtttccacgagcacgtgtaagtggaagtagctctctcccttctcaaattgcacaaagaaaagggcctccgg ggccttactcacacggcgccactccgtcagaaagtcgcgctgcagcttctcggccacggtcaggggtgcctgctcaatcagattcag atccaagtcagaatctggcggcaactcccactccttctcggccacccagttcacaaagctgtcagaaatgccgggcagatgctcgtc aaggtcgctggggaccttaatcacaatctcgtaaaaccccgccagggcggcagatccgcgcccgatggtGCGGCCGCacg gtatgaataatccggaatatttataggtttttttattacaaaactgttacgaaaacagtaaaatacttatttatttgcgagatggttatcatttta attatctccatgatctattaatattcACGCGTcggagtatacggacctttaattcaacccaacacaatatattatagttaaataagaatt attatcaaatcatttgtatattaattaaaatactatactgtaaattacattttatttacaatcaatactagtaaaaggtaggttcaaccactgatg cctaggcacaccgaaacgactaaccctaattcttatcctttacttcaggcgcgcccggcttaagcgtacgTACGGTGTATTT TAGATTTCACAAACAATTACGAAAGGACTACAATACTTATTTTatgtcttttgttgatcaccctcc agattggttggaagaagttggtgaaggtcttcgcgagtttttgggccttgaagcgggcccaccgaaaccaaaacccaatcagcagca tcaagatcaagcccgtggtcttgtgctgcctggttataactatctcggacccggaaacggtctcgatcgaggagagcctgtcaacagg gcagacgaggtcgcgcgagagcacgacatctcgtacaacgagcagcttgaggcgggagacaacccctacctcaagtacaaccac gcggacgccgagtttcaggagaagctcgccgacgacacatccttcgggggaaacctcggaaaggcagtctttcaggccaagaaaa gggttctcgaaccttttggcctggttgaagagggtgctaagacggcccctaccggaaagcggatagacgaccactttccaaaaagaa agaaggctcggaccgaagaggactccaagccttccacctcgtcagacgccgaagctggacccagcggatcccagcagctgcaaa tcccagcccaaccagcctcaagtttgggagctgatacaatgtctgcgggaggtggcggcccattgggcgacaataaccaaggtgcc gatggagtgggcaatgcctcgggagattggcattgcgattccacgtggatgggggacagagtcgtcaccaagtccacccgaacctg ggtgctgcccagctacaacaaccaccagtaccgagagatcaaaagcggctccglcgacggaagcaacgccaacgcctactttgga tacagcaccccctgggggtactttgactttaaccgcttccacagccactggagcccccgagactggcaaagactcatcaacaactact ggggcttcagaccccggtccctcagagtcaaaatcttcaacattcaagtcaaagaggtcacggtgcaggactccaccaccaccatcg ccaacaacctcacctccaccgtccaagtgtttacggacgacgactaccagctgccctacgtcgtcggcaacgggaccgagggatgc ctgccggccttccctccgcaggtctttacgctgccgcagtacggttacgcgacgctgaaccgcgacaacacagaaaatcccaccga gaggagcagcttcttctgcctagagtactttcccagcaagatgctgagaacgggcaacaactttgagtttacctacaactttgaggagg tgcccttccactccagcttcgctcccagtcagaacctcttcaagctggccaacccgctggtggaccagtacttgtaccgcttcgtgagc acaaataacactggcggagtccagttcaacaagaacctggccgggagatacgccaacacctacaaaaactggttcccggggccca tgggccgaacccagggctggaacctgggctccggggtcaaccgcgccagtgtcagcgccttcgccacgaccaataggatggagc tcgagggcgcgagttaccaggtgcccccgcagccgaacggcatgaccaacaacctccagggcagcaacacctatgccctggaga acactatgatcttcaacagccagccggcgaacccgggcaccaccgccacgtacctcgagggcaacatgctcatcaccagcgagag cgagacgcagccggtgaaccgcgtggcgtacaacgtcggcgggcagatggccaccaacaaccagagctccaccactgcccccg cgaccggcacgtacaacctccaggaaatcgtgcccggcagcgtgtggatggagagggacgtgtacctccaaggacccatctggg ccaagatcccagagacgggggcgcactttcacccctctccggccatgggcggattcggactcaaacacccaccgcccatgatgctc atcaagaacacgcctgtgcccggaaatatcaccagcttctcggacgtgcccgtcagcagcttcatcacccagtacagcaccgggca ggtcaccgtggagatggagtgggagctcaagaaggaaaactccaagaggtggaacccagagatccagtacacaaacaactacaa cgacccccagtttgtggactttgccccggacagcaccggggaatacagaaccaccagacctatcggaacccgataccttacccgac ccctttaagctagcagctgatgcatagcatgcggtaccgggagatgggggaggctaactgaaacacggaaggagacaataccgga aggaacccgcgctatgacggcaataaaaagacagaataaaacgcacgggtgttgggtcgtttgttcGAGTCATTTAAAT ACCGGTCTGGGCGAACAAACGATGCTCGCCTTCCAGAAAACCGAGGATGCGAAC CACTTCATCCGGGGTCAGCACCACCGGCAAGCGCCGCGACGGCCGAGGTCTTCC GATCTCCTGAAGCCAGGGCAGATCCGTGCACAGCACCTTGCCGTAGAAGAACAG CAAGGCCGCCAATGCCTGACGATGCGTGGAGACCGAAACCTTGCGCTCGTTCGCCAGCCAGGACAGAAATGCCTCGACTTCGCTGCTGCCCAAGGTTGCCGGGTGACG CACACCGTGGAAACGGATGAAGGCACGAACCCAGTTGACATAAGCCTGTTCGGT TCGTAAACTGTAATGCAAGTAGCGTATGCGCTCACGCAACTGGTCCAGAACCTTG AGC TTC TG TA TA TC TG GC TAA CG AC GG TG CT TG AG TT GA CA CC TG CG GC GG GC CA AG TT CG CG AC AG GG CT AT GT CT AC AA GT CG GG CC GTT TG TAT CTA GT CG CA GC TT GGGTCGATGTTTGATGTTATGGAGCAGCAACGATGTTACGCAGCAGCAACGATGT TACGCAGCAGGGCAGTCGCCCTAAAACAAAGTTAGGTGGCTCAAGTATGGGCAT CATTCGCACATGTAGGCTCGGCCCTGACCAAGTCAAATCCATGCGGGCTGCTCTT GATCTTTTCGGTCGTGAGTTCGGAGACGTAGCCACCTACTCCCAACATCAGCCGG ACTCCGATTACCTCGGGAACTTGCTCCGTAGTAAGACATTCATCGCGCTTGCTGC CTTCGACCAAGAAGCGGTTGTTGGCGCTCTCGCGGCTTACGTTCTGCCCAAGTTT GAGCAGCCGCGTAGTGAGATCTATATCTATGATCTCGCAGTCTCCGGCGAGCACC GGAGGCAGGGCATTGCCACCGCGCTCATCAATCTCCTCAAGCATGAGGCCAACG CGCTTGGTGCTTATGTGATCTACGTGCAAGCAGATTACGGTGACGATCCCGCAGT GGCTCTCTATACAAAGTTGGGCATACGGGAAGAAGTGATGCACTTTGATATCGAC CCAAGTACCGCCACCTAACAATTCGTTCAAGCCGAGATCGGCTTCCCGGCCGCGG AGTTGTTCGGTAAATTGTCACAACGCCGCGAATATAGTCTTTACCATGCCCTTGGC CACGCCCCTCTTTAATACGACGGGCAATTTGCACTTCAGAAAATGAAGAGTTTGC TTTAGCCATAACAAAAGTCCAGTATGCTTTTTCACAGCATAACTGGACTGATTTCA GTTTACAACTATTCTGTCTAGTTTAAGACTTTATTGTCATAGTTTAGATCTATTTTGT TCAGTTTAAGACTTTATTGTCCGCCCACACCCGCTTACGCAGGGCATCCATTTATT ACTCAAatcggatcccgggcccgtcgactgcagaggcctgcatgcaagcttggcgtaatcatggtcatagctgtttcctgtgtg aaattgttatccgctcacaattccacacaacatacgagccggaagcataaagtgtaaagcctggggtgcctaatgagtgagctaactc acattaattgcgttgcgctcactgcccgctttccagtcgggaaacctgtcgtgccagctgcattaatgaatcggccaacgcgcgggga gaggcggtttgcgtattgggcgctcttccgcttcctcgctcactgactcgctgcgctcggtcgttcggctgcggcgagcggtatcagc tcactcaaaggcggtaatacggttatccacagaatcaggggataacgcaggaaagaacatgtgagcaaaaggccagcaaaaggcc aggaaccgtaaaaaggccgcgttgctggcgtttttccataggctccgcccccctgacgagcatcacaaaaatcgacgctcaagtcag aggtggcgaaacccgacaggactataaagataccaggcgtttccccctggaagctccctcgtgcgctctcctgttccgaccctgccg cttaccggatacctgtccgcctttctcccttcgggaagcgtggcgctUctcatagctcacgctgtaggtatctcagttcggtgtaggtcg ttcgctccaagctgggctgtgtgcacgaaccccccgttcagcccgaccgctgcgccttatccggtaactatcgtcttgagtccaaccc ggtaagacacgacttatcgccactggcagcagccactggtaacaggattagcagagcgaggtatgtaggcggtgctacagagttctt gaagtggtggcctaactacggctacactagaagaacagtatttggtatctgcgctctgctgaagccagttaccttcggaaaaagagttg gtagctcttgatccggcaaacaaaccaccgctggtagcggtggtttttttgtttgcaagcagcagattacgcgcagaaaaaaaggatct caagaagatcctttgatcttttctacggggtctgacgctcagtggaacgaaaactcacgttaagggattttggtcatgagattatcaaaa aggatcttcacctagatccttttaaattaaaaatgaagttttaaatcaatctaaagtatatatgagtaaacttggtctgacagttaccaatgct taatcagtgaggcacctatctcagcgatctgtctatttcgttcatccatagttgcctgactccccgtcgtgtagataactacgatacggga gggcttaccatctggccccagtgctgcaatgataccgcgagacccacgctcaccggctccagatttatcagcaataaaccagccagc cggaagggccgagcgcagaagtggtcctgcaactttatccgcctccatccagtctattaattgttgccgggaagctagagtaagtagt tcgccagttaatagtttgcgcaacgttgttgccattgctacaggcatcgtggtgtcacgctcgtcgtttggtatggcttcattcagctccg gttcccaacgatcaaggcgagttacatgatcccccatgttgtgcaaaaaagcggttagctccttcggtcctccgatcgttgtcagaagt aagttggccgcagtgttatcactcatggttatggcagcactgcataattctcttactgtcatgccatccgtaagatgcttttctgtgactggt gagtactcaaccaagtcattctgagaatagtgtatgcggcgaccgagttgctcttgcccggcgtcaatacgggataataccgcgccac atagcagaactttaaaagtgctcatcattggaaaacgttcttcggggcgaaaactctcaaggatcttaccgctgttgagatccagttcga tgtaacccactcgtgcacccaactgatcttcagcatcttttactttcaccagcgtttctgggtgagcaaaaacaggaaggcaaaatgcc gcaaaaaagggaataagggcgacacggaaatgttgaatactcatactcttcctttttcaatattattgaagcatttatcagggttattgtct catgagcggatacatatttgaatgtatttagaaaaataaacaaataggggttccgcgcacatttccccgaaaagtgccacctgacgtct aagaaaccattattatcatgacattaacctataaaaataggcgtatcacgaggccctttcgtcpFBacX-AAVRep2ACap5_40CE EoNPV (SEQ ID NO: 36) tcgcgcgtttcggtgatgacggtgaaaacctctgacacatgcagctcccggagacggtcacagcttgtctgtaagcggatgccggga gcagacaagcccgtcagggcgcgtcagcgggtgttggcgggtgtcggggctggcttaactatgcggcatcagagcagattgtact gagagtgcaccatatgcggtgtgaaataccgcacagatgcgtaaggagaaaataccgcatcaggcgccattcgccattcaggctgc gcaactgttgggaagggcgatcggtgcgggcctcttcgctattacgccagctggcgaaagggggatgtgctgcaaggcgattaagt tgggtaacgccagggttttcccagtcacgacgttgtaaaacgacggccagtgaattcgagctcggtacctcgcgaatgcatctagat GATTAAAAACATAACAGGAAGAAAAATGCCCCGCTGTGGGCGGACAAAATAGTT GGGAACTGGGAGGGGTGGAAATGGAGTTTTTAAGGATTATTTAGGGAAGAGTGA CAAAATAGATGGGAACTGGGTGTAGCGTCGTAAGCTAATACGAAAATTAAAAATG ACAAAATAGTTTGGAACTAGATTTCACTTATCTGGTTcggatctgggtccccctaggctcaagcagt gatcagatccagacatgataagatacattgatgagtttggacaaaccacaactagaatgcagtgaaaaaaatgctttatttgtgaaattt gtgatgctattgctttattlgtaaccattataagctgcaataaacaagttaacaacaacaattgcattcattttatgtttcaggttcaggggga ggtgtgggaggttttttaaagcaagtaaaacctctacaaatgtggtatggctgattatgatcctctagtacttctcgacaagcttgtcgag actgcaggctctagagtcgacctgcaggcatgcaagcttgattcctcgagtttattgttcaaagatgcagtcatccaaatccacattgac cagatcgcaggcagtgcaagcgtctggcacctttcccatgatatgatgaatgtagcacagtttctgatacgcctttttgacgacagaaa cgggttgagattctgacacgggaaagcactctaaacagtctttctgtccgtgagtgaagcagatatttgaattctgattcattctctcgcat tgtctgcagggaaacagcatcagattcatgcccacgtgacgagaacatttgttttggtacctgtctgcgtagttgatcgaagcttccgcg tctgacgtcgatggctgcgcaactgactcgcgcacccgtttgggctcacttatatctgcgtcactgggggcgggtcttttcttggctcca ccctttttgacgtagaattcatgctccacctcaaccacgtgatcctttgcccaccggaaaaagtctttgacttcctgcttggtgaccttccc aaagtcatgatccagacggcgggtgagttcaaatttgaacatccggtcttgcaacggctgctggtgttcgaaggtcgttgagttcccgt caatcacggcgcacatgttggtgttggaggtgacgatcacgggagtcgggtctatctgggccgaggacttgcatttctggtccacgc gcaccttgcttcctccgagaatggctttggccgactccacgaccttggcggtcatcttcccctcctcccaccagatcaccatcttgtcga cacagtcgttgaagggaaagttctcattggtccagtttacgcacccgtagaagggcacagtgtgggctatggcctccgcgatgttggt cttcccggtagttgcaggcccaaacagccagatggtgttcctcttgccgaactttttcgtggcccatcccagaaagacggaagccgca tattggggatcgtacccgtttagttccaaaattttataaatccgattgctggaaatgtcctccacgggctgctggcccaccaggtagtcg ggggcggttttagtcaggctcataatctttcccgcattgtccaaggcagccttgatttgggaccgcgagttggaggccgcattgaagg agatgtatgaAgcctggtcctcctggatccactgcttctccgaggtaatccccttgtccacgagccacccgaccagctccatgtacct ggctgaagtttttgatctgatcaccggcgcgtcagaattgggattctgattctctttgttctgctcctgcgtctgcgacacgtgcgtcagat gctgcgccaccaaccgtttacgctccgtgagattcaaacaggcgcttaaatactgttctaaattagtccacgcccactggagctcagg ctgggttttggggagcaagtaattggggatgtagcactcgtccaccaccttgttcccgcctccggcgccgtttctggtctttgtgaccgc gaaccagtttggcaaagtcggctcgatcccgcggtaaattctctgaatcagtttttcgcgaatctgactcaggaaacgtcccaaaacta aggatttcaccccggtggtttccacgagcacgtgtaagtggaagtagctctctcccttctcaaattgcacaaagaaaagggcctccgg ggccttactcacacggcgccactccgtcagaaagtcgcgctgcagcttctcggccacggtcaggggtgcctgctcaatcagattcag atccaagtcagaatctggcggcaactcccactccttctcggccacccagttcacaaagctgtcagaaatgccgggcagatgctcgtc aaggtcgctggggaccttaatcacaatctcgtaaaaccccgccagggcggcagatccgcgcccgatggtGCGGCCGCacg gtatgaataatccggaatatttataggtttttttattacaaaactgttacgaaaacagtaaaatacttatttatttgcgagatggttatcatttta attatctccatgatctattaatattcACGCGTcggagtatacggacctttaattcaacccaacacaatatattatagttaaataagaatt attatcaaatcatttgtatattaattaaaatactatactgtaaattacattttatttacaatcaatactagtaaaaggtaggttcaaccactgatg cctaggcacaccgaaacgactaaccctaattcttatcctttacttcaggcgcgcccggcttaagcgtacgTACGGTGTATTT TAGATTTCACAAACAATTACGAAAGGACTACAATACTTGTTTTatgtcttttgttgatcaccctcc agattggttggaagaagttggtgaaggtcttcgcgagtttttgggccttgaagcgggcccaccgaaaccaaaacccaatcagcagca tcaagatcaagcccgtggtcttgtgctgcctggttataactatctcggacccggaaacggtctcgatcgaggagagcctgtcaacagg gcagacgaggtcgcgcgagagcacgacatctcgtacaacgagcagcttgaggcgggagacaacccctacctcaagtacaaccac gcggacgccgagtttcaggagaagctcgccgacgacacatccttcgggggaaacctcggaaaggcagtctttcaggccaagaaaa gggttctcgaaccttttggcctggttgaagagggtgctaagacggcccctaccggaaagcggatagacgaccactttccaaaaagaa agaaggctcggaccgaagaggactccaagccttccacctcgtcagacgccgaagctggacccagcggatcccagcagctgcaaa tcccagcccaaccagcctcaagtttgggagctgatacaatgtctgcgggaggtggcggcccattgggcgacaataaccaaggtgcc gatggagtgggcaatgcctcgggagattggcattgcgattccacgtggatgggggacagagtcgtcaccaagtccacccgaacctgggtgctgcccagctacaacaaccaccagtaccgagagatcaaaagcggctccgtcgacggaagcaacgccaacgcctactttgga tacagcaccccctgggggtactttgactttaaccgcttccacagccactggagcccccgagactggcaaagactcatcaacaactact ggggcttcagaccccggtccctcagagtcaaaatcttcaacattcaagtcaaagaggtcacggtgcaggactccaccaccaccatcg ccaacaacctcacctccaccgtccaagtgtttacggacgacgactaccagctgccctacgtcgtcggcaacgggaccgagggatgc ctgccggccttccctccgcaggtctttacgctgccgcagtacggttacgcgacgctgaaccgcgacaacacagaaaatcccaccga gaggagcagcttcttctgcctagagtactttcccagcaagatgctgagaacgggcaacaactttgagtttacctacaactttgaggagg tgcccttccactccagcttcgctcccagtcagaacctcttcaagctggccaacccgctggtggaccagtacttgtaccgcttcgtgagc acaaataacactggcggagtccagttcaacaagaacctggccgggagatacgccaacacctacaaaaactggttcccggggccca tgggccgaacccagggctggaacctgggctccggggtcaaccgcgccagtgtcagcgccttcgccacgaccaataggatggagc tcgagggcgcgagttaccaggtgcccccgcagccgaacggcatgaccaacaacctccagggcagcaacacctatgccctggaga acactatgatcttcaacagccagccggcgaacccgggcaccaccgccacgtacctcgagggcaacatgctcatcaccagcgagag cgagacgcagccggtgaaccgcgtggcgtacaacgtcggcgggcagatggccaccaacaaccagagctccaccactgcccccg cgaccggcacgtacaacctccaggaaatcgtgcccggcagcgtgtggatggagagggacgtgtacctccaaggacccatctggg ccaagatcccagagacgggggcgcactttcacccctctccggccatgggcggattcggactcaaacacccaccgcccatgatgctc atcaagaacacgcctgtgcccggaaatatcaccagcttctcggacgtgcccgtcagcagcttcatcacccagtacagcaccgggca ggtcaccgtggagatggagtgggagctcaagaaggaaaactccaagaggtggaacccagagatccagtacacaaacaactacaa cgacccccagtttgtggactttgccccggacagcaccggggaatacagaaccaccagacctatcggaacccgataccttacccgac ccctttaagctagcagctgatgcatagcatgcggtaccgggagatgggggaggctaactgaaacacggaaggagacaataccgga aggaacccgcgctatgacggcaataaaaagacagaataaaacgcacgggtgttgggtcgtttgttcGAGTCATTTAAAT ACCGGTCTGGGCGAACAAACGATGCTCGCCTTCCAGAAAACCGAGGATGCGAAC CACTTCATCCGGGGTCAGCACCACCGGCAAGCGCCGCGACGGCCGAGGTCTTCC GATCTCCTGAAGCCAGGGCAGATCCGTGCACAGCACCTTGCCGTAGAAGAACAG CAAGGCCGCCAATGCCTGACGATGCGTGGAGACCGAAACCTTGCGCTCGTTCGC CAGCCAGGACAGAAATGCCTCGACTTCGCTGCTGCCCAAGGTTGCCGGGTGACG CACACCGTGGAAACGGATGAAGGCACGAACCCAGTTGACATAAGCCTGTTCGGT TCGTAAACTGTAATGCAAGTAGCGTATGCGCTCACGCAACTGGTCCAGAACCTTG AGC TTC TG TA TA TC TG GC TAA CG AC GG TG CT TG AG TT GA CA CC TG CG GC GG GC CA AG TT CG CG AC AG GG CT AT GT CT AC AA GT CG GG CC GTT TG TAT CTA GT CG CA GC TT GGGTCGATGTTTGATGTTATGGAGCAGCAACGATGTTACGCAGCAGCAACGATGT TACGCAGCAGGGCAGTCGCCCTAAAACAAAGTTAGGTGGCTCAAGTATGGGCAT CATTCGCACATGTAGGCTCGGCCCTGACCAAGTCAAATCCATGCGGGCTGCTCTT GATCTTTTCGGTCGTGAGTTCGGAGACGTAGCCACCTACTCCCAACATCAGCCGG ACTCCGATTACCTCGGGAACTTGCTCCGTAGTAAGACATTCATCGCGCTTGCTGC CTTCGACCAAGAAGCGGTTGTTGGCGCTCTCGCGGCTTACGTTCTGCCCAAGTTT GAGCAGCCGCGTAGTGAGATCTATATCTATGATCTCGCAGTCTCCGGCGAGCACC GGAGGCAGGGCATTGCCACCGCGCTCATCAATCTCCTCAAGCATGAGGCCAACG CGCTTGGTGCTTATGTGATCTACGTGCAAGCAGATTACGGTGACGATCCCGCAGT GGCTCTCTATACAAAGTTGGGCATACGGGAAGAAGTGATGCACTTTGATATCGAC CCAAGTACCGCCACCTAACAATTCGTTCAAGCCGAGATCGGCTTCCCGGCCGCGG AGTTGTTCGGTAAATTGTCACAACGCCGCGAATATAGTCTTTACCATGCCCTTGGC CACGCCCCTCTTTAATACGACGGGCAATTTGCACTTCAGAAAATGAAGAGTTTGC TTTAGCCATAACAAAAGTCCAGTATGCTTTTTCACAGCATAACTGGACTGATTTCA GTTTACAACTATTCTGTCTAGTTTAAGACTTTATTGTCATAGTTTAGATCTATTTTGT TCAGTTTAAGACTTTATTGTCCGCCCACACCCGCTTACGCAGGGCATCCATTTATT ACTCAAatcggatcccgggcccgtcgactgcagaggcctgcatgcaagcttggcgtaatcatggtcatagctgtttcctgtgtg aaattgttatccgctcacaattccacacaacatacgagccggaagcataaagtgtaaagcctggggtgcctaatgagtgagctaactc acattaattgcgttgcgctcactgcccgctttccagtcgggaaacctgtcgtgccagctgcattaatgaatcggccaacgcgcgggga gaggcggtttgcgtattgggcgctcttccgcttcctcgctcactgactcgctgcgctcggtcgttcggctgcggcgagcggtatcagc tcactcaaaggcggtaatacggttatccacagaatcaggggataacgcaggaaagaacatgtgagcaaaaggccagcaaaaggccaggaaccgtaaaaaggccgcgttgctggcgtttttccataggctccgcccccctgacgagcatcacaaaaatcgacgctcaagtcag aggtggcgaaacccgacaggactataaagataccaggcgtttccccctggaagctccctcgtgcgctctcctgttccgaccctgccg cttaccggatacctgtccgcctttctcccttcgggaagcgtggcgctttctcatagctcacgctgtaggtatctcagttcggtgtaggtcg ttcgctccaagctgggctgtgtgcacgaaccccccgttcagcccgaccgctgcgccttatccggtaactatcgtcttgagtccaaccc ggtaagacacgacttatcgccactggcagcagccactggtaacaggattagcagagcgaggtatgtaggcggtgctacagagttctt gaagtggtggcctaactacggctacactagaagaacagtatttggtatctgcgctctgctgaagccagttaccttcggaaaaagagttg gtagctcttgatccggcaaacaaaccaccgctggtagcggtggtttttttgtttgcaagcagcagattacgcgcagaaaaaaaggatct caagaagatcctttgatcttttctacggggtctgacgctcagtggaacgaaaactcacgttaagggattttggtcatgagattatcaaaa aggatcttcacctagatccttttaaattaaaaatgaagttttaaatcaatctaaagtatatatgagtaaacttggtctgacagttaccaatgct taatcagtgaggcacctatctcagcgatctgtctatttcgttcatccatagttgcctgactccccgtcgtgtagataactacgatacggga gggcttaccatctggccccagtgctgcaatgataccgcgagacccacgctcaccggctccagatttatcagcaataaaccagccagc cggaagggccgagcgcagaagtggtcctgcaactttatccgcctccatccagtctattaattgttgccgggaagctagagtaagtagt tcgccagttaatagtttgcgcaacgttgttgccattgctacaggcatcgtggtgtcacgctcgtcgtttggtatggcttcattcagctccg gttcccaacgatcaaggcgagttacatgatcccccatgttgtgcaaaaaagcggttagctccttcggtcctccgatcgttgtcagaagt aagttggccgcagtgttatcactcatggttatggcagcactgcataattctcttactgtcatgccatccgtaagatgcttttctgtgactggt gagtactcaaccaagtcattctgagaatagtgtatgcggcgaccgagttgctcttgcccggcgtcaatacgggataataccgcgccac atagcagaactttaaaagtgctcatcattggaaaacgttcttcggggcgaaaactctcaaggatcttaccgctgttgagatccagttcga tgtaacccactcgtgcacccaactgatcttcagcatcttttactttcaccagcgtttctgggtgagcaaaaacaggaaggcaaaatgcc gcaaaaaagggaataagggcgacacggaaatgttgaatactcatactcttcctttttcaatattattgaagcatttatcagggttattgtct catgagcggatacatatttgaatgtatttagaaaaataaacaaataggggttccgcgcacatttccccgaaaagtgccacctgacgtct aagaaaccattattatcatgacattaacctataaaaataggcgtatcacgaggccctttcgtc pFBacX-AAVRep2ACap5_40AE L21 (SEQ ID NO: 37) tcgcgcgtttcggtgatgacggtgaaaacctctgacacatgcagctcccggagacggtcacagcttgtctgtaagcggatgccggga gcagacaagcccgtcagggcgcgtcagcgggtgttggcgggtgtcggggctggcttaactatgcggcatcagagcagattgtact gagagtgcaccatatgcggtgtgaaataccgcacagatgcgtaaggagaaaataccgcatcaggcgccattcgccattcaggctgc gcaactgttgggaagggcgatcggtgcgggcctcttcgctattacgccagctggcgaaagggggatgtgctgcaaggcgattaagt tgggtaacgccagggttttcccagtcacgacgttgtaaaacgacggccagtgaattcgagctcggtacctcgcgaatgcatctagat GATTAAAAACATAACAGGAAGAAAAATGCCCCGCTGTGGGCGGACAAAATAGTT GGGAACTGGGAGGGGTGGAAATGGAGTTTTTAAGGATTATTTAGGGAAGAGTGA CAAAATAGATGGGAACTGGGTGTAGCGTCGTAAGCTAATACGAAAATTAAAAATG ACAAAATAGTTTGGAACTAGATTTCACTTATCTGGTTcggatctgggtccccctaggctcaagcagt gatcagatccagacatgataagatacattgatgagtttggacaaaccacaactagaatgcagtgaaaaaaatgctttatttgtgaaattt gtgatgctattgctttatttgtaaccattataagctgcaataaacaagttaacaacaacaattgcattcattttatgtttcaggttcaggggga ggtgtgggaggttttttaaagcaagtaaaacctctacaaatgtggtatggctgattatgatcctctagtacttctcgacaagcttgtcgag actgcaggctctagagtcgacctgcaggcatgcaagcttgattcctcgagtttattgttcaaagatgcagtcatccaaatccacattgac cagatcgcaggcagtgcaagcgtctggcacctttcccatgatatgatgaatgtagcacagtttctgatacgcctttttgacgacagaaa cgggttgagattctgacacgggaaagcactctaaacagtctttctgtccgtgagtgaagcagatatttgaattctgattcattctctcgcat tgtctgcagggaaacagcatcagattcatgcccacgtgacgagaacatttgttttggtacctgtctgcgtagttgatcgaagcttccgcg tctgacgtcgatggctgcgcaactgactcgcgcacccgtttgggctcacttatatctgcgtcactgggggcgggtcttttcttggctcca ccctttttgacgtagaattcatgctccacctcaaccacgtgatcctttgcccaccggaaaaagtctttgacttcctgcttggtgaccttccc aaagtcatgatccagacggcgggtgagttcaaatttgaacatccggtcttgcaacggctgctggtgttcgaaggtcgttgagttcccgt caatcacggcgcacatgttggtgttggaggtgacgatcacgggagtcgggtctatctgggccgaggacttgcatttctggtccacgc gcaccttgcttcctccgagaatggctttggccgactccacgaccttggcggtcatcttcccctcctcccaccagatcaccatcttgtcga cacagtcgttgaagggaaagttctcattggtccagtttacgcacccgtagaagggcacagtgtgggctatggcctccgcgatgttggt cttcccggtagttgcaggcccaaacagccagatggtgttcctcttgccgaactttttcgtggcccatcccagaaagacggaagccgcatattggggatcgtacccgtttagttccaaaattttataaatccgattgctggaaatgtcctccacgggctgctggcccaccaggtagtcg ggggcggttttagtcaggctcataatctttcccgcattgtccaaggcagccttgatttgggaccgcgagttggaggccgcattgaagg agatgtatgaAgcctggtcctcctggatccactgcttctccgaggtaatccccttgtccacgagccacccgaccagctccatgtacct ggctgaagtttttgatctgatcaccggcgcgtcagaattgggattctgattctctttgttctgctcctgcgtctgcgacacgtgcgtcagat gctgcgccaccaaccgtttacgctccgtgagattcaaacaggcgcttaaatactgttctaaattagtccacgcccactggagctcagg ctgggttttggggagcaagtaattggggatgtagcactcgtccaccaccttgttcccgcctccggcgccgtttctggtctttgtgaccgc gaaccagtttggcaaagtcggctcgatcccgcggtaaattctctgaatcagtttttcgcgaatctgactcaggaaacgtcccaaaacta aggatttcaccccggtggtttccacgagcacgtgtaagtggaagtagctctctcccttctcaaattgcacaaagaaaagggcctccgg ggccttactcacacggcgccactccgtcagaaagtcgcgctgcagcttctcggccacggtcaggggtgcctgctcaatcagattcag atccaagtcagaatctggcggcaactcccactccttctcggccacccagttcacaaagctgtcagaaatgccgggcagatgctcgtc aaggtcgctggggaccttaatcacaatctcgtaaaaccccgccagggcggcagatccgcgcccgatggtGCGGCCGCacg gtatgaataatccggaatatttataggtttttttattacaaaactgttacgaaaacagtaaaatacttatttatttgcgagatggttatcatttta attatctccatgatctattaatattcACGCGTcggagtatacggacctttaattcaacccaacacaatatattatagttaaataagaatt attatcaaatcatttgtatattaattaaaatactatactgtaaattacattttatttacaatcaatactagtaaaaggtaggttcaaccactgatg cctaggcacaccgaaacgactaaccctaattcttatcctttacttcaggcgcgcccggcttaagcgtacgAACTCCTAAAA AACCGCCACCTATTTTatgtcttttgttgatcaccctccagattggttggaagaagttggtgaaggtcttcgcgagtttttgg gccttgaagcgggcccaccgaaaccaaaacccaatcagcagcatcaagatcaagcccgtggtcttgtgctgcctggttataactatct cggacccggaaacggtctcgatcgaggagagcctgtcaacagggcagacgaggtcgcgcgagagcacgacatctcgtacaacg agcagcttgaggcgggagacaacccctacctcaagtacaaccacgcggacgccgagtttcaggagaagctcgccgacgacacat ccttcgggggaaacctcggaaaggcagtctttcaggccaagaaaagggttctcgaaccttttggcctggttgaagagggtgctaaga cggcccctaccggaaagcggatagacgaccactttccaaaaagaaagaaggctcggaccgaagaggactccaagccttccacctc gtcagacgccgaagctggacccagcggatcccagcagctgcaaatcccagcccaaccagcctcaagtttgggagctgatacaatg tctgcgggaggtggcggcccattgggcgacaataaccaaggtgccgatggagtgggcaatgcctcgggagattggcattgcgatt ccacgtggatgggggacagagtcgtcaccaagtccacccgaacctgggtgctgcccagctacaacaaccaccagtaccgagagat caaaagcggctccgtcgacggaagcaacgccaacgcctactttggatacagcaccccctgggggtactttgactttaaccgcttcca cagccactggagcccccgagactggcaaagactcatcaacaactactggggcttcagaccccggtccctcagagtcaaaatcttca acattcaagtcaaagaggtcacggtgcaggactccaccaccaccatcgccaacaacctcacctccaccgtccaagtgtttacggacg acgactaccagctgccctacgtcgtcggcaacgggaccgagggatgcctgccggccttccctccgcaggtctttacgctgccgcag tacggttacgcgacgctgaaccgcgacaacacagaaaatcccaccgagaggagcagctlcttctgcctagagtactttcccagcaa gatgctgagaacgggcaacaactttgagtttacctacaactttgaggaggtgcccttccactccagcttcgctcccagtcagaacctctt caagctggccaacccgctggtggaccagtacttgtaccgcttcgtgagcacaaataacactggcggagtccagttcaacaagaacct ggccgggagatacgccaacacctacaaaaactggttcccggggcccatgggccgaacccagggctggaacctgggctccgggg tcaaccgcgccagtgtcagcgccttcgccacgaccaataggatggagctcgagggcgcgagttaccaggtgcccccgcagccga acggcatgaccaacaacctccagggcagcaacacctatgccctggagaacactatgatcttcaacagccagccggcgaacccggg caccaccgccacgtacctcgagggcaacatgctcatcaccagcgagagcgagacgcagccggtgaaccgcgtggcgtacaacgt cggcgggcagatggccaccaacaaccagagctccaccactgcccccgcgaccggcacgtacaacctccaggaaatcgtgcccg gcagcgtgtggatggagagggacgtgtacctccaaggacccatctgggccaagatcccagagacgggggcgcactttcacccctc tccggccatgggcggattcggactcaaacacccaccgcccatgatgctcatcaagaacacgcctgtgcccggaaatatcaccagctt ctcggacgtgcccgtcagcagcttcatcacccagtacagcaccgggcaggtcaccgtggagatggagtgggagctcaagaagga aaactccaagaggtggaacccagagatccagtacacaaacaactacaacgacccccagtttgtggactttgccccggacagcaccg gggaatacagaaccaccagacctatcggaacccgataccttacccgacccctttaagctagcagctgatgcatagcatgcggtaccg ggagatgggggaggctaactgaaacacggaaggagacaataccggaaggaacccgcgctatgacggcaataaaaagacagaat aaaacgcacgggtgttgggtcgtttgttcGAGTCATTTAAATACCGGTCTGGGCGAACAAACGATG CTCGCCTTCCAGAAAACCGAGGATGCGAACCACTTCATCCGGGGTCAGCACCAC CGGCAAGCGCCGCGACGGCCGAGGTCTTCCGATCTCCTGAAGCCAGGGCAGATC CGTGCACAGCACCTTGCCGTAGAAGAACAGCAAGGCCGCCAATGCCTGACGATG CGTGGAGACCGAAACCTTGCGCTCGTTCGCCAGCCAGGACAGAAATGCCTCGAC TTCGCTGCTGCCCAAGGTTGCCGGGTGACGCACACCGTGGAAACGGATGAAGGC ACGAACCCAGTTGACATAAGCCTGTTCGGTTCGTAAACTGTAATGCAAGTAGCGTATGCGCTCACGCAACTGGTCCAGAACCTTGACCGAACGCAGCGGTGGTAACGGC GCAGTGGCGGTTTTCATGGCTTGTTATGACTGTTTTTTTGTACAGTCTATGCCTCG GGCATCCAAGCAGCAAGCGCGTTACGCCGTGGGTCGATGTTTGATGTTATGGAGC AGCAACGATGTTACGCAGCAGCAACGATGTTACGCAGCAGGGCAGTCGCCCTAA AACAAAGTTAGGTGGCTCAAGTATGGGCATCATTCGCACATGTAGGCTCGGCCCT GACCAAGTCAAATCCATGCGGGCTGCTCTTGATCTTTTCGGTCGTGAGTTCGGAG ACGTAGCCACCTACTCCCAACATCAGCCGGACTCCGATTACCTCGGGAACTTGCT CCGTAGTAAGACATTCATCGCGCTTGCTGCCTTCGACCAAGAAGCGGTTGTTGGC GCTCTCGCGGCTTACGTTCTGCCCAAGTTTGAGCAGCCGCGTAGTGAGATCTATAT CTATGATCTCGCAGTCTCCGGCGAGCACCGGAGGCAGGGCATTGCCACCGCGCT CATCAATCTCCTCAAGCATGAGGCCAACGCGCTTGGTGCTTATGTGATCTACGTGC AAGCAGATTACGGTGACGATCCCGCAGTGGCTCTCTATACAAAGTTGGGCATACG GGAAGAAGTGATGCACTTTGATATCGACCCAAGTACCGCCACCTAACAATTCGTT CAAGCCGAGATCGGCTTCCCGGCCGCGGAGTTGTTCGGTAAATTGTCACAACGC CGCGAATATAGTCTTTACCATGCCCTTGGCCACGCCCCTCTTTAATACGACGGGCA ACT TT TT TG TTC CA AC CT ATC GA CG ATA AA AA CA TT GG GA AA CG TA GG AT TT TT TG CC AT GT TT TA TG AC CC AA AT CA TA AC TA TA CA TGA TG CT TC AC GA TG TT TA AT AG GACTTTATTGTCATAGTTTAGATCTATTTTGTTCAGTTTAAGACTTTATTGTCCGCC CACACCCGCTTACGCAGGGCATCCATTTATTACTCAAatcggatcccgggcccgtcgactgcagag gcctgcatgcaagcttggcgtaatcatggtcatagctgtttcctgtgtgaaattgttatccgctcacaattccacacaacatacgagccg gaagcataaagtgtaaagcctggggtgcctaatgagtgagctaactcacattaattgcgttgcgctcactgcccgctttccagtcggga aacctgtcgtgccagctgcattaatgaatcggccaacgcgcggggagaggcggtttgcgtattgggcgctcttccgcttcctcgctca ctgactcgctgcgctcggtcgttcggctgcggcgagcggtatcagctcactcaaaggcggtaatacggttatccacagaatcagggg ataacgcaggaaagaacatgtgagcaaaaggccagcaaaaggccaggaaccgtaaaaaggccgcgttgctggcgtttttccatag gctccgcccccctgacgagcatcacaaaaatcgacgctcaagtcagaggtggcgaaacccgacaggactataaagataccaggc gtttccccctggaagctccctcgtgcgctctcctgttccgaccctgccgcttaccggatacctgtccgcctttctcccttcgggaagcgt ggcgctttctcatagctcacgctgtaggtatctcagUcggtgtaggtcgttcgctccaagctgggctgtgtgcacgaaccccccgttca gcccgaccgctgcgccttatccggtaactatcgtcttgagtccaacccggtaagacacgacttatcgccactggcagcagccactgg taacaggattagcagagcgaggtatgtaggcggtgctacagagttcttgaagtggtggcctaaclacggctacactagaagaacagt atttggtatctgcgctctgctgaagccagttaccttcggaaaaagagttggtagctcttgatccggcaaacaaaccaccgctggtagcg gtggtttttttgtttgcaagcagcagattacgcgcagaaaaaaaggatctcaagaagatcctttgatcttttctacggggtctgacgctca gtggaacgaaaactcacgttaagggattttggtcatgagattatcaaaaaggatcttcacctagatccttttaaattaaaaatgaagtttta aatcaatctaaagtatatatgagtaaacttggtctgacagttaccaatgcttaatcagtgaggcacctatctcagcgatctgtctatttcgtt catccatagttgcctgactccccgtcgtgtagataactacgatacgggagggcttaccatctggccccagtgctgcaatgataccgcg agacccacgctcaccggctccagatttatcagcaataaaccagccagccggaagggccgagcgcagaagtggtcctgcaactttat ccgcctccatccagtctattaattgttgccgggaagctagagtaagtagttcgccagttaatagtttgcgcaacgttgttgccattgctac aggcatcgtggtgtcacgctcgtcgtttggtatggcttcattcagctccggttcccaacgatcaaggcgagttacatgatcccccatgtt gtgcaaaaaagcggttagctccttcggtcctccgatcgttgtcagaagtaagttggccgcagtgttatcactcatggttatggcagcact gcataattctcttactgtcatgccatccgtaagatgcttttctgtgactggtgagtactcaaccaagtcattctgagaatagtgtatgcggc gaccgagttgctcttgcccggcgtcaatacgggataataccgcgccacatagcagaactttaaaagtgctcatcattggaaaacgttct tcggggcgaaaactctcaaggatcttaccgctgttgagatccagttcgatgtaacccactcgtgcacccaactgatcttcagcatctttt actttcaccagcgtttctgggtgagcaaaaacaggaaggcaaaatgccgcaaaaaagggaataagggcgacacggaaatgttgaat actcatactcttcctttttcaatattattgaagcatttatcagggttattgtctcatgagcggatacatatttgaatgtatttagaaaaataaaca aataggggttccgcgcacatttccccgaaaagtgccacctgacgtctaagaaaccattattatcatgacattaacctataaaaataggc gtatcacgaggccctttcgtc pFBacX-AAVRep2ACap5_40AE Syn21 (SEQ ID NO: 38)tcgcgcgtttcggtgatgacggtgaaaacctctgacacatgcagctcccggagacggtcacagcttgtctgtaagcggatgccggga gcagacaagcccgtcagggcgcgtcagcgggtgttggcgggtgtcggggctggcttaactatgcggcatcagagcagattgtact gagagtgcaccatatgcggtgtgaaataccgcacagatgcgtaaggagaaaataccgcatcaggcgccattcgccattcaggctgc gcaactgttgggaagggcgatcggtgcgggcctcttcgctattacgccagctggcgaaagggggatgtgctgcaaggcgattaagt tgggtaacgccagggttttcccagtcacgacgttgtaaaacgacggccagtgaattcgagctcggtacctcgcgaatgcatctagat GATTAAAAACATAACAGGAAGAAAAATGCCCCGCTGTGGGCGGACAAAATAGTT GGGAACTGGGAGGGGTGGAAATGGAGTTTTTAAGGATTATTTAGGGAAGAGTGA CAAAATAGATGGGAACTGGGTGTAGCGTCGTAAGCTAATACGAAAATTAAAAATG ACAAAATAGTTTGGAACTAGATTTCACTTATCTGGTTcggatctgggtccccctaggctcaagcagt gatcagatccagacatgataagatacattgatgagtttggacaaaccacaactagaatgcagtgaaaaaaatgctttatttgtgaaattt gtgatgctattgctttatttgtaaccattataagctgcaataaacaagttaacaacaacaattgcattcattttatgtttcaggttcaggggga ggtgtgggaggttttttaaagcaagtaaaacctctacaaatgtggtatggctgattatgatcctctagtacttctcgacaagcttgtcgag actgcaggctctagagtcgacctgcaggcatgcaagcttgattcctcgagtttattgttcaaagatgcagtcatccaaatccacattgac cagatcgcaggcagtgcaagcgtctggcacctttcccatgatatgatgaatgtagcacagtttctgatacgcctttttgacgacagaaa cgggttgagattctgacacgggaaagcactctaaacagtctttctgtccgtgagtgaagcagatatttgaattctgattcattctctcgcat tgtctgcagggaaacagcatcagattcatgcccacgtgacgagaacatttgttttggtacctgtctgcgtagttgatcgaagcttccgcg tctgacgtcgatggctgcgcaactgactcgcgcacccgtttgggctcacttatatctgcgtcactgggggcgggtcttttcttggctcca ccctttttgacgtagaattcatgctccacctcaaccacgtgatcctttgcccaccggaaaaagtctttgacttcctgcttggtgaccttccc aaagtcatgatccagacggcgggtgagttcaaatttgaacatccggtcttgcaacggctgctggtgttcgaaggtcgttgagttcccgt caatcacggcgcacatgttggtgttggaggtgacgatcacgggagtcgggtctatctgggccgaggacttgcatttctggtccacgc gcaccttgcttcctccgagaatggctttggccgactccacgaccttggcggtcatcttcccctcctcccaccagatcaccatcttgtcga cacagtcgttgaagggaaagttctcattggtccagtttacgcacccgtagaagggcacagtgtgggctatggcctccgcgatgttggt cttcccggtagttgcaggcccaaacagccagatggtgttcctcttgccgaactttttcgtggcccatcccagaaagacggaagccgca tattggggatcgtacccgtttagttccaaaattttataaatccgattgctggaaatgtcctccacgggctgctggcccaccaggtagtcg ggggcggttttagtcaggctcataatctttcccgcattgtccaaggcagccttgatttgggaccgcgagttggaggccgcattgaagg agatgtatgaAgcctggtcctcctggatccactgcttctccgaggtaatccccttgtccacgagccacccgaccagctccatgtacct ggctgaagtUttgatctgatcaccggcgcgtcagaattgggattctgaUctctttgUctgctcctgcgtctgcgacacgtgcgtcagat gctgcgccaccaaccgtttacgctccgtgagattcaaacaggcgcttaaatactgttctaaattagtccacgcccactggagctcagg ctgggttttggggagcaagtaaUggggatgtagcactcgtccaccaccttgttcccgcctccggcgccgtttctggtctttgtgaccgc gaaccagtttggcaaagtcggctcgatcccgcggtaaattctctgaatcagtttttcgcgaatctgactcaggaaacgtcccaaaacta aggatttcaccccggtggtttccacgagcacgtgtaagtggaagtagctctctcccttctcaaattgcacaaagaaaagggcctccgg ggccttactcacacggcgccactccgtcagaaagtcgcgctgcagcttctcggccacggtcaggggtgcctgctcaatcagattcag atccaagtcagaatctggcggcaactcccactccttctcggccacccagttcacaaagctgtcagaaatgccgggcagatgctcgtc aaggtcgctggggaccttaatcacaatctcgtaaaaccccgccagggcggcagatccgcgcccgatggtGCGGCCGCacg gtatgaataatccggaatatttataggtttttttattacaaaactgttacgaaaacagtaaaatacttatttatttgcgagatggttatcatttta attatctccatgatctattaatattcACGCGTcggagtatacggacctttaattcaacccaacacaatatattatagttaaataagaatt attatcaaatcatttgtatattaattaaaatactatactgtaaattacattttatttacaatcaatactagtaaaaggtaggttcaaccactgatg cctaggcacaccgaaacgactaaccctaattcttatcctttacttcaggcgcgcccggcttaagcgtacgaacttaaaaaaaaaaatca aaTATTTTatgtcttttgttgatcaccctccagattggttggaagaagttggtgaaggtcttcgcgagtttttgggccttgaagcggg cccaccgaaaccaaaacccaatcagcagcatcaagatcaagcccgtggtcttgtgctgcctggttataactatctcggacccggaaa cggtctcgatcgaggagagcctgtcaacagggcagacgaggtcgcgcgagagcacgacatctcgtacaacgagcagcttgaggc gggagacaacccctacctcaagtacaaccacgcggacgccgagtttcaggagaagctcgccgacgacacatccttcgggggaaa cctcggaaaggcagtctttcaggccaagaaaagggttctcgaaccttttggcctggttgaagagggtgctaagacggcccctaccgg aaagcggatagacgaccactttccaaaaagaaagaaggctcggaccgaagaggactccaagccttccacctcgtcagacgccgaa gctggacccagcggatcccagcagctgcaaatcccagcccaaccagcctcaagtttgggagctgatacaatgtctgcgggaggtg gcggcccattgggcgacaataaccaaggtgccgatggagtgggcaatgcctcgggagattggcattgcgattccacgtggatggg ggacagagtcgtcaccaagtccacccgaacctgggtgctgcccagctacaacaaccaccagtaccgagagatcaaaagcggctcc gtcgacggaagcaacgccaacgcctactttggatacagcaccccctgggggtactttgactttaaccgcttccacagccactggagc ccccgagactggcaaagactcatcaacaactactggggcttcagaccccggtccctcagagtcaaaatcttcaacattcaagtcaaagaggtcacggtgcaggactccaccaccaccatcgccaacaacctcacctccaccgtccaagtgtttacggacgacgactaccagct gccctacgtcgtcggcaacgggaccgagggatgcctgccggccttccctccgcaggtctttacgctgccgcagtacggttacgcga cgctgaaccgcgacaacacagaaaatcccaccgagaggagcagcttcttctgcctagagtactttcccagcaagatgctgagaacg ggcaacaactttgagtttacctacaactttgaggaggtgcccttccactccagcttcgctcccagtcagaacctcttcaagctggccaa cccgctggtggaccagtacttgtaccgcttcgtgagcacaaataacactggcggagtccagttcaacaagaacctggccgggagat acgccaacacctacaaaaactggttcccggggcccatgggccgaacccagggctggaacctgggctccggggtcaaccgcgcca gtgtcagcgccttcgccacgaccaataggatggagctcgagggcgcgagttaccaggtgcccccgcagccgaacggcatgacca acaacctccagggcagcaacacctatgccctggagaacactatgatcttcaacagccagccggcgaacccgggcaccaccgcca cgtacctcgagggcaacatgctcatcaccagcgagagcgagacgcagccggtgaaccgcgtggcgtacaacgtcggcgggcag atggccaccaacaaccagagctccaccactgcccccgcgaccggcacgtacaacctccaggaaatcgtgcccggcagcgtgtgg atggagagggacgtgtacctccaaggacccatctgggccaagatcccagagacgggggcgcactttcacccctctccggccatgg gcggattcggactcaaacacccaccgcccatgatgctcatcaagaacacgcctgtgcccggaaatatcaccagcttctcggacgtgc ccgtcagcagcttcatcacccagtacagcaccgggcaggtcaccgtggagatggagtgggagctcaagaaggaaaactccaaga ggtggaacccagagatccagtacacaaacaactacaacgacccccagtttgtggactttgccccggacagcaccggggaatacag aaccaccagacctatcggaacccgataccttacccgacccctttaagctagcagctgatgcatagcatgcggtaccgggagatggg ggaggctaactgaaacacggaaggagacaataccggaaggaacccgcgctatgacggcaataaaaagacagaataaaacgcac gggtgttgggtcgtttgttcGAGTCATTTAAATACCGGTCTGGGCGAACAAACGATGCTCGCC TTCCAGAAAACCGAGGATGCGAACCACTTCATCCGGGGTCAGCACCACCGGCAA GCGCCGCGACGGCCGAGGTCTTCCGATCTCCTGAAGCCAGGGCAGATCCGTGCA CAGCACCTTGCCGTAGAAGAACAGCAAGGCCGCCAATGCCTGACGATGCGTGGA GACCGAAACCTTGCGCTCGTTCGCCAGCCAGGACAGAAATGCCTCGACTTCGCT GCTGCCCAAGGTTGCCGGGTGACGCACACCGTGGAAACGGATGAAGGCACGAACCCAGTTGACATAAGCCTGTTCGGTTCGTAAACTGTAATGCAAGTAGCGTATGCG CTCACGCAACTGGTCCAGAACCTTGACCGAACGCAGCGGTGGTAACGGCGCAGT GGCGGTTTTCATGGCTTGTTATGACTGTTTTTTTGTACAGTCTATGCCTCGGGCAT CCAAGCAGCAAGCGCGTTACGCCGTGGGTCGATGTTTGATGTTATGGAGCAGCA ACGATGTTACGCAGCAGCAACGATGTTACGCAGCAGGGCAGTCGCCCTAAAACA AAGTTAGGTGGCTCAAGTATGGGCATCATTCGCACATGTAGGCTCGGCCCTGACC AAGTCAAATCCATGCGGGCTGCTCTTGATCTTTTCGGTCGTGAGTTCGGAGACGT AGCCACCTACTCCCAACATCAGCCGGACTCCGATTACCTCGGGAACTTGCTCCGT AGTAAGACATTCATCGCGCTTGCTGCCTTCGACCAAGAAGCGGTTGTTGGCGCTC TCGCGGCTTACGTTCTGCCCAAGTTTGAGCAGCCGCGTAGTGAGATCTATATCTAT GATCTCGCAGTCTCCGGCGAGCACCGGAGGCAGGGCATTGCCACCGCGCTCATC AATCTCCTCAAGCATGAGGCCAACGCGCTTGGTGCTTATGTGATCTACGTGCAAG CAGATTACGGTGACGATCCCGCAGTGGCTCTCTATACAAAGTTGGGCATACGGGA AGAAGTGATGCACTTTGATATCGACCCAAGTACCGCCACCTAACAATTCGTTCAA GCCGAGATCGGCTTCCCGGCCGCGGAGTTGTTCGGTAAATTGTCACAACGCCGC GAATATAGTCTTTACCATGCCCTTGGCCACGCCCCTCTTTAATACGACGGGCAATT TGCACTTCAGAAAATGAAGAGTTTGCTTTAGCCATAACAAAAGTCCAGTATGCTT TTTCACAGCATAACTGGACTGATTTCAGTTTACAACTATTCTGTCTAGTTTAAGAC TTTATTGTCATAGTTTAGATCTATTTTGTTCAGTTTAAGACTTTATTGTCCGCCCAC ACCCGCTTACGCAGGGCATCCATTTATTACTCAAatcggatcccgggcccgtcgactgcagaggcct gcatgcaagcttggcgtaatcatggtcatagctgtttcctgtgtgaaattgttatccgctcacaattccacacaacatacgagccggaag cataaagtgtaaagcctggggtgcctaatgagtgagctaactcacattaattgcgttgcgctcactgcccgctttccagtcgggaaacc tgtcgtgccagctgcattaatgaatcggccaacgcgcggggagaggcggtttgcgtattgggcgctcttccgcttcctcgctcactga ctcgctgcgctcggtcgttcggctgcggcgagcggtatcagctcactcaaaggcggtaatacggttatccacagaatcaggggataa cgcaggaaagaacatgtgagcaaaaggccagcaaaaggccaggaaccgtaaaaaggccgcgttgctggcgtttttccataggctc cgcccccctgacgagcatcacaaaaatcgacgctcaagtcagaggtggcgaaacccgacaggactataaagataccaggcgtttc cccctggaagctccctcgtgcgctctcctgttccgaccctgccgcttaccggatacctgtccgcctttctcccttcgggaagcgtggcgctttctcatagctcacgctgtaggtatctcagttcggtgtaggtcgttcgctccaagctgggctgtgtgcacgaaccccccgttcagccc gaccgctgcgccttatccggtaactatcgtcttgagtccaacccggtaagacacgacttatcgccactggcagcagccactggtaaca ggattagcagagcgaggtatgtaggcggtgctacagagttcttgaagtggtggcctaactacggctacactagaagaacagtatttg gtatctgcgctctgctgaagccagttaccttcggaaaaagagttggtagctcttgatccggcaaacaaaccaccgctggtagcggtgg tttttttgtttgcaagcagcagattacgcgcagaaaaaaaggatctcaagaagatcctttgatcttttctacggggtctgacgctcagtgg aacgaaaactcacgttaagggattttggtcatgagattatcaaaaaggatcttcacctagatccttttaaattaaaaatgaagttttaaatc aatctaaagtatatatgagtaaacttggtctgacagttaccaatgcttaatcagtgaggcacctatctcagcgatctgtctatttcgttcatc catagttgcctgactccccgtcgtgtagataactacgatacgggagggcttaccatctggccccagtgctgcaatgataccgcgagac ccacgctcaccggctccagatttatcagcaataaaccagccagccggaagggccgagcgcagaagtggtcctgcaactttatccgc ctccatccagtctattaattgttgccgggaagctagagtaagtagttcgccagttaatagtttgcgcaacgttgttgccattgctacaggc atcgtggtgtcacgctcgtcgtttggtatggcttcattcagctccggttcccaacgatcaaggcgagttacatgatcccccatgttgtgca aaaaagcggttagctccttcggtcctccgatcgttgtcagaagtaagttggccgcagtgttatcactcatggttatggcagcactgcata attctcttactgtcatgccatccgtaagatgcttttctgtgactggtgagtactcaaccaagtcattctgagaatagtgtatgcggcgaccg agttgctcttgcccggcgtcaatacgggataataccgcgccacatagcagaactttaaaagtgctcatcattggaaaacgttcttcggg gcgaaaactctcaaggatcttaccgctgttgagatccagttcgatgtaacccactcgtgcacccaactgatcttcagcatcttttactttca ccagcgtttctgggtgagcaaaaacaggaaggcaaaatgccgcaaaaaagggaataagggcgacacggaaatgttgaatactcat actcttcctttttcaatattattgaagcatttatcagggttattgtctcatgagcggatacatatttgaatgtatttagaaaaataaacaaatag gggttccgcgcacatttccccgaaaagtgccacctgacgtctaagaaaccattattatcatgacattaacctataaaaataggcgtatca cgaggccctttcgtc pFBacX-AAVRep2ACap5_40AE TMV (SEQ ID NO: 39) tcgcgcgtttcggtgatgacggtgaaaacctctgacacatgcagctcccggagacggtcacagcttgtctgtaagcggatgccggga gcagacaagcccgtcagggcgcgtcagcgggtgttggcgggtgtcggggctggcttaactatgcggcatcagagcagattgtact gagagtgcaccatatgcggtgtgaaataccgcacagatgcgtaaggagaaaataccgcatcaggcgccattcgccattcaggctgc gcaactgttgggaagggcgatcggtgcgggcctcttcgctattacgccagctggcgaaagggggatgtgctgcaaggcgattaagt tgggtaacgccagggttttcccagtcacgacgttgtaaaacgacggccagtgaattcgagctcggtacctcgcgaatgcatctagat GATTAAAAACATAACAGGAAGAAAAATGCCCCGCTGTGGGCGGACAAAATAGTT GGGAACTGGGAGGGGTGGAAATGGAGTTTTTAAGGATTATTTAGGGAAGAGTGA CAAAATAGATGGGAACTGGGTGTAGCGTCGTAAGCTAATACGAAAATTAAAAATG ACAAAATAGTTTGGAACTAGATTTCACTTATCTGGTTcggatctgggtccccctaggctcaagcagt gatcagatccagacatgataagatacattgatgagtttggacaaaccacaactagaatgcagtgaaaaaaatgctttatttgtgaaattt gtgatgctattgctttatttgtaaccattataagctgcaataaacaagttaacaacaacaattgcattcattttatgtttcaggttcaggggga ggtgtgggaggttttttaaagcaagtaaaacctctacaaatgtggtatggctgattatgatcctctagtacttctcgacaagcttgtcgag actgcaggctctagagtcgacctgcaggcatgcaagcttgattcctcgagtttattgttcaaagatgcagtcatccaaatccacattgac cagatcgcaggcagtgcaagcgtctggcacctttcccatgatatgatgaatgtagcacagtttctgatacgcctttttgacgacagaaa cgggttgagattctgacacgggaaagcactctaaacagtctttctgtccgtgagtgaagcagatatttgaattctgattcattctctcgcat tgtctgcagggaaacagcatcagattcatgcccacgtgacgagaacatttgttttggtacctgtctgcgtagttgatcgaagcttccgcg tctgacgtcgatggctgcgcaactgactcgcgcacccgtttgggctcacttatatctgcgtcactgggggcgggtcttttcttggctcca ccctttttgacgtagaattcatgctccacctcaaccacgtgatcctttgcccaccggaaaaagtctttgacttcctgcttggtgaccttccc aaagtcatgatccagacggcgggtgagttcaaatttgaacatccggtcttgcaacggctgctggtgttcgaaggtcgttgagttcccgt caatcacggcgcacatgttggtgttggaggtgacgatcacgggagtcgggtctatctgggccgaggacttgcatttctggtccacgc gcaccttgcttcctccgagaatggctttggccgactccacgaccttggcggtcatcttcccctcctcccaccagatcaccatcttgtcga cacagtcgttgaagggaaagttctcattggtccagtttacgcacccgtagaagggcacagtgtgggctatggcctccgcgatgttggt cttcccggtagttgcaggcccaaacagccagatggtgttcctcttgccgaactttttcgtggcccatcccagaaagacggaagccgca tattggggatcgtacccgtttagttccaaaattttataaatccgattgctggaaatgtcctccacgggctgctggcccaccaggtagtcg ggggcggttttagtcaggctcataatctttcccgcattgtccaaggcagccttgatttgggaccgcgagttggaggccgcattgaaggagatgtatgaAgcctggtcctcctggatccactgcttctccgaggtaatccccttgtccacgagccacccgaccagctccatgtacct ggctgaagtttttgatctgatcaccggcgcgtcagaattgggattctgattctctttgttctgctcctgcgtctgcgacacgtgcgtcagat gctgcgccaccaaccgtttacgctccgtgagattcaaacaggcgcttaaatactgttctaaattagtccacgcccactggagctcagg ctgggttttggggagcaagtaattggggatgtagcactcgtccaccaccttgttcccgcctccggcgccgtttctggtctttgtgaccgc gaaccagtttggcaaagtcggctcgatcccgcggtaaattctctgaatcagtttttcgcgaatctgactcaggaaacgtcccaaaacta aggatttcaccccggtggtttccacgagcacgtgtaagtggaagtagctctctcccttctcaaattgcacaaagaaaagggcctccgg ggccttactcacacggcgccactccgtcagaaagtcgcgctgcagcttctcggccacggtcaggggtgcctgctcaatcagattcag atccaagtcagaatctggcggcaactcccactccttctcggccacccagttcacaaagctgtcagaaatgccgggcagatgctcgtc aaggtcgctggggaccttaatcacaatctcgtaaaaccccgccagggcggcagatccgcgcccgatggtGCGGCCGCacg gtatgaataatccggaatatttataggtttttttattacaaaactgttacgaaaacagtaaaatacttatttatttgcgagatggttatcatttta attatctccatgatctattaatattcACGCGTcggagtatacggacctttaattcaacccaacacaatatattatagttaaataagaatt attatcaaatcatttgtatattaattaaaatactatactgtaaattacattttatttacaatcaatactagtaaaaggtaggttcaaccactgatg cctaggcacaccgaaacgactaaccctaattcttatcctttacttcaggcgcgcccggcttaagcgtacgGTATTTTTACAA CAATTACCAACAACAACAAACCAACAAACAACATTACAATTACTATTTACAATTA CTATTTTatgtcttttgttgatcaccctccagattggttggaagaagttggtgaaggtcttcgcgagtttttgggccttgaagcgggc ccaccgaaaccaaaacccaatcagcagcatcaagatcaagcccgtggtcttgtgctgcctggttataactatctcggacccggaaac ggtctcgatcgaggagagcctgtcaacagggcagacgaggtcgcgcgagagcacgacatctcgtacaacgagcagcttgaggcg ggagacaacccctacctcaagtacaaccacgcggacgccgagtttcaggagaagctcgccgacgacacatccttcgggggaaac ctcggaaaggcagtctttcaggccaagaaaagggttctcgaaccttttggcctggttgaagagggtgctaagacggcccctaccgga aagcggatagacgaccactttccaaaaagaaagaaggctcggaccgaagaggactccaagccttccacctcgtcagacgccgaa gctggacccagcggatcccagcagctgcaaatcccagcccaaccagcctcaagtttgggagctgatacaatgtctgcgggaggtg gcggcccattgggcgacaataaccaaggtgccgatggagtgggcaatgcctcgggagattggcattgcgattccacgtggatggg ggacagagtcgtcaccaagtccacccgaacctgggtgctgcccagctacaacaaccaccagtaccgagagatcaaaagcggctcc gtcgacggaagcaacgccaacgcctactttggatacagcaccccctgggggtactttgactttaaccgcttccacagccactggagc ccccgagactggcaaagactcatcaacaactactggggcttcagaccccggtccctcagagtcaaaatcttcaacattcaagtcaaa gaggtcacggtgcaggactccaccaccaccatcgccaacaacctcacctccaccgtccaagtgtttacggacgacgactaccagct gccctacgtcgtcggcaacgggaccgagggatgcctgccggccttccctccgcaggtctttacgctgccgcagtacggttacgcga cgctgaaccgcgacaacacagaaaatcccaccgagaggagcagcttcttctgcctagagtactttcccagcaagatgctgagaacg ggcaacaactttgagtttacctacaactttgaggaggtgcccttccactccagcttcgctcccagtcagaacctcttcaagctggccaa cccgctggtggaccagtacttgtaccgcttcgtgagcacaaataacactggcggagtccagttcaacaagaacctggccgggagat acgccaacacctacaaaaactggttcccggggcccatgggccgaacccagggctggaacctgggctccggggtcaaccgcgcca gtgtcagcgccttcgccacgaccaataggatggagctcgagggcgcgagttaccaggtgcccccgcagccgaacggcatgacca acaacctccagggcagcaacacctatgccctggagaacactatgatcttcaacagccagccggcgaacccgggcaccaccgcca cgtacctcgagggcaacatgctcatcaccagcgagagcgagacgcagccggtgaaccgcgtggcgtacaacgtcggcgggcag atggccaccaacaaccagagctccaccactgcccccgcgaccggcacgtacaacctccaggaaatcgtgcccggcagcgtgtgg atggagagggacgtgtacctccaaggacccatctgggccaagatcccagagacgggggcgcactttcacccctctccggccatgg gcggattcggactcaaacacccaccgcccatgatgctcatcaagaacacgcctgtgcccggaaatatcaccagcttctcggacgtgc ccgtcagcagcttcatcacccagtacagcaccgggcaggtcaccgtggagatggagtgggagctcaagaaggaaaactccaaga ggtggaacccagagatccagtacacaaacaactacaacgacccccagtttgtggactttgccccggacagcaccggggaatacag aaccaccagacctatcggaacccgataccttacccgacccctttaagctagcagctgatgcatagcatgcggtaccgggagatggg ggaggctaactgaaacacggaaggagacaataccggaaggaacccgcgctatgacggcaataaaaagacagaataaaacgcac gggtgttgggtcgtttgttcGAGTCATTTAAATACCGGTCTGGGCGAACAAACGATGCTCGCC TTCCAGAAAACCGAGGATGCGAACCACTTCATCCGGGGTCAGCACCACCGGCAA GCGCCGCGACGGCCGAGGTCTTCCGATCTCCTGAAGCCAGGGCAGATCCGTGCA CAGCACCTTGCCGTAGAAGAACAGCAAGGCCGCCAATGCCTGACGATGCGTGGA GACCGAAACCTTGCGCTCGTTCGCCAGCCAGGACAGAAATGCCTCGACTTCGCT GCTGCCCAAGGTTGCCGGGTGACGCACACCGTGGAAACGGATGAAGGCACGAA CCCAGTTGACATAAGCCTGTTCGGTTCGTAAACTGTAATGCAAGTAGCGTATGCG CTCACGCAACTGGTCCAGAACCTTGACCGAACGCAGCGGTGGTAACGGCGCAGTGGCGGTTTTCATGGCTTGTTATGACTGTTTTTTTGTACAGTCTATGCCTCGGGCAT CCAAGCAGCAAGCGCGTTACGCCGTGGGTCGATGTTTGATGTTATGGAGCAGCA ACGATGTTACGCAGCAGCAACGATGTTACGCAGCAGGGCAGTCGCCCTAAAACA AAGTTAGGTGGCTCAAGTATGGGCATCATTCGCACATGTAGGCTCGGCCCTGACC AAGTCAAATCCATGCGGGCTGCTCTTGATCTTTTCGGTCGTGAGTTCGGAGACGT AGCCACCTACTCCCAACATCAGCCGGACTCCGATTACCTCGGGAACTTGCTCCGT AGTAAGACATTCATCGCGCTTGCTGCCTTCGACCAAGAAGCGGTTGTTGGCGCTC TCGCGGCTTACGTTCTGCCCAAGTTTGAGCAGCCGCGTAGTGAGATCTATATCTAT GATCTCGCAGTCTCCGGCGAGCACCGGAGGCAGGGCATTGCCACCGCGCTCATC AATCTCCTCAAGCATGAGGCCAACGCGCTTGGTGCTTATGTGATCTACGTGCAAG CAGATTACGGTGACGATCCCGCAGTGGCTCTCTATACAAAGTTGGGCATACGGGA AGAAGTGATGCACTTTGATATCGACCCAAGTACCGCCACCTAACAATTCGTTCAA GCCGAGATCGGCTTCCCGGCCGCGGAGTTGTTCGGTAAATTGTCACAACGCCGC GAATATAGTCTTTACCATGCCCTTGGCCACGCCCCTCTTTAATACGACGGGCAATT TGCACTTCAGAAAATGAAGAGTTTGCTTTAGCCATAACAAAAGTCCAGTATGCTT TTTCACAGCATAACTGGACTGATTTCAGTTTACAACTATTCTGTCTAGTTTAAGAC TTTATTGTCATAGTTTAGATCTATTTTGTTCAGTTTAAGACTTTATTGTCCGCCCAC ACCCGCTTACGCAGGGCATCCATTTATTACTCAAatcggatcccgggcccgtcgactgcagaggcct gcatgcaagcttggcgtaatcatggtcatagctgtttcctgtgtgaaattgttatccgctcacaattccacacaacatacgagccggaag cataaagtgtaaagcctggggtgcctaatgagtgagctaactcacattaattgcgttgcgctcactgcccgctttccagtcgggaaacc tgtcgtgccagctgcattaatgaatcggccaacgcgcggggagaggcggtttgcgtattgggcgctcttccgcttcctcgctcactga ctcgctgcgctcggtcgttcggctgcggcgagcggtatcagctcactcaaaggcggtaatacggttatccacagaatcaggggataa cgcaggaaagaacatgtgagcaaaaggccagcaaaaggccaggaaccgtaaaaaggccgcgttgctggcgtttttccataggctc cgcccccctgacgagcatcacaaaaatcgacgctcaagtcagaggtggcgaaacccgacaggactataaagataccaggcgtttc cccctggaagctccctcgtgcgctctcctgttccgaccctgccgcttaccggatacctgtccgcctttctcccttcgggaagcgtggcg ctttctcatagctcacgctgtaggtatctcagttcggtgtaggtcgttcgctccaagctgggctgtgtgcacgaaccccccgttcagccc gaccgctgcgccttatccggtaactatcgtcttgagtccaacccggtaagacacgacltatcgccactggcagcagccactggtaaca ggattagcagagcgaggtatgtaggcggtgctacagagttcttgaagtggtggcctaactacggctacactagaagaacagtatttg gtatctgcgctctgctgaagccagttaccttcggaaaaagagttggtagctcttgatccggcaaacaaaccaccgctggtagcggtgg tttttttgtttgcaagcagcagattacgcgcagaaaaaaaggatctcaagaagatcctttgatcttttctacggggtctgacgctcagtgg aacgaaaactcacgttaagggattttggtcatgagattatcaaaaaggatcttcacctagatccttttaaattaaaaatgaagttttaaatc aatctaaagtatatatgagtaaacttggtctgacagttaccaatgcttaatcagtgaggcacctatctcagcgatctgtctatttcgttcatc catagttgcctgactccccgtcgtgtagataactacgatacgggagggcttaccatctggccccagtgctgcaatgataccgcgagac ccacgctcaccggctccagatttatcagcaataaaccagccagccggaagggccgagcgcagaagtggtcctgcaactttatccgc ctccatccagtctattaattgttgccgggaagctagagtaagtagttcgccagttaatagtttgcgcaacgttgttgccattgctacaggc atcgtggtgtcacgctcgtcgtttggtatggcttcattcagctccggttcccaacgatcaaggcgagttacatgatcccccatgttgtgca aaaaagcggttagctccttcggtcctccgatcgttgtcagaagtaagttggccgcagtgttatcactcatggttatggcagcactgcata attctcttactgtcatgccatccgtaagatgcttttctgtgactggtgagtactcaaccaagtcattctgagaatagtgtatgcggcgaccg agttgctcttgcccggcgtcaatacgggataataccgcgccacatagcagaactttaaaagtgctcatcattggaaaacgttcttcggg gcgaaaactctcaaggatcttaccgctgttgagatccagttcgatgtaacccactcgtgcacccaactgatcttcagcatcttttactttca ccagcgtttctgggtgagcaaaaacaggaaggcaaaatgccgcaaaaaagggaataagggcgacacggaaatgttgaatactcat actcttcctttttcaatattattgaagcatttatcagggttattgtctcatgagcggatacatatttgaatgtatttagaaaaataaacaaatag gggttccgcgcacatttccccgaaaagtgccacctgacgtctaagaaaccattattatcatgacattaacctataaaaataggcgtatca cgaggccctttcgtc pFBacX-AAVRep2ACap5_40CE AcNPV (SEQ ID NO: 40) tcgcgcgtttcggtgatgacggtgaaaacctctgacacatgcagctcccggagacggtcacagcttgtctgtaagcggatgccggga gcagacaagcccgtcagggcgcgtcagcgggtgttggcgggtgtcggggctggcttaactatgcggcatcagagcagattgtactgagagtgcaccatatgcggtgtgaaataccgcacagatgcgtaaggagaaaataccgcatcaggcgccattcgccattcaggctgc gcaactgttgggaagggcgatcggtgcgggcctcttcgctattacgccagctggcgaaagggggatgtgctgcaaggcgattaagt tgggtaacgccagggttttcccagtcacgacgttgtaaaacgacggccagtgaattcgagctcggtacctcgcgaatgcatctagat GATTAAAAACATAACAGGAAGAAAAATGCCCCGCTGTGGGCGGACAAAATAGTT GGGAACTGGGAGGGGTGGAAATGGAGTTTTTAAGGATTATTTAGGGAAGAGTGA CAAAATAGATGGGAACTGGGTGTAGCGTCGTAAGCTAATACGAAAATTAAAAATG ACAAAATAGTTTGGAACTAGATTTCACTTATCTGGTTcggatctgggtccccctaggctcaagcagt gatcagatccagacatgataagatacattgatgagtttggacaaaccacaactagaatgcagtgaaaaaaatgctttatttgtgaaattt gtgatgctattgctttatttgtaaccattataagctgcaataaacaagttaacaacaacaattgcattcattttatgtttcaggttcaggggga ggtgtgggaggttttttaaagcaagtaaaacctctacaaatgtggtatggctgattatgatcctctagtacttctcgacaagcttgtcgag actgcaggctctagagtcgacctgcaggcatgcaagcttgattcctcgagtttattgttcaaagatgcagtcatccaaatccacattgac cagatcgcaggcagtgcaagcgtctggcacctttcccatgatatgatgaatgtagcacagtttctgatacgcctttttgacgacagaaa cgggttgagattctgacacgggaaagcactctaaacagtctttctgtccgtgagtgaagcagatatttgaattctgattcattctctcgcat tgtctgcagggaaacagcatcagattcatgcccacgtgacgagaacatttgttttggtacctgtctgcgtagttgatcgaagcttccgcg tctgacgtcgatggctgcgcaactgactcgcgcacccgtttgggctcacttatatctgcgtcactgggggcgggtcttttcttggctcca ccctttttgacgtagaattcatgctccacctcaaccacgtgatcctttgcccaccggaaaaagtctttgacttcctgcttggtgaccttccc aaagtcatgatccagacggcgggtgagttcaaatttgaacatccggtcttgcaacggctgctggtgttcgaaggtcgttgagttcccgt caatcacggcgcacatgttggtgttggaggtgacgatcacgggagtcgggtctatctgggccgaggacttgcatttctggtccacgc gcaccttgcttcctccgagaatggctttggccgactccacgaccttggcggtcatcttcccctcctcccaccagatcaccatcttgtcga cacagtcgttgaagggaaagttctcattggtccagtttacgcacccgtagaagggcacagtgtgggctatggcctccgcgatgttggt cttcccggtagttgcaggcccaaacagccagatggtgttcctcttgccgaactttttcgtggcccatcccagaaagacggaagccgca tattggggatcgtacccgtttagttccaaaattttataaatccgattgctggaaatgtcctccacgggctgctggcccaccaggtagtcg ggggcggttttagtcaggctcataatctttcccgcattgtccaaggcagccttgatttgggaccgcgagttggaggccgcattgaagg agatgtatgaAgcctggtcctcctggatccactgcttctccgaggtaatccccttgtccacgagccacccgaccagctccatgtacct ggctgaagtttttgatctgatcaccggcgcgtcagaattgggattctgattctctttgttctgctcctgcgtctgcgacacgtgcgtcagat gctgcgccaccaaccgtttacgctccgtgagattcaaacaggcgcttaaatactgttctaaattagtccacgcccactggagctcagg ctgggttttggggagcaagtaaUggggatgtagcactcgtccaccaccttgttcccgcctccggcgccgtttctggtctttgtgaccgc gaaccagtttggcaaagtcggctcgatcccgcggtaaattctctgaatcagtttttcgcgaatctgactcaggaaacgtcccaaaacta aggatttcaccccggtggtttccacgagcacgtgtaagtggaagtagctctctcccttctcaaattgcacaaagaaaagggcctccgg ggccttactcacacggcgccactccgtcagaaagtcgcgctgcagcttctcggccacggtcaggggtgcctgctcaatcagattcag atccaagtcagaatctggcggcaactcccactccttctcggccacccagttcacaaagctgtcagaaatgccgggcagatgctcgtc aaggtcgctggggaccttaatcacaatctcgtaaaaccccgccagggcggcagatccgcgcccgatggtGCGGCCGCacg gtatgaataatccggaatatttataggtttttttattacaaaactgttacgaaaacagtaaaatacttatttatttgcgagatggttatcatttta attatctccatgatctattaatattcACGCGTcggagtatacggacctttaattcaacccaacacaatatattatagttaaataagaatt attatcaaatcatttgtatattaattaaaatactatactgtaaattacattttatttacaatcaatactagtaaaaggtaggttcaaccactgatg cctaggcacaccgaaacgactaaccctaattcttatcctttacttcaggcgcgcccggcttaagcgtacgAATTACAAATTA TATAACAAAtTGTTTTatgtcttttgttgatcaccctccagattggttggaagaagttggtgaaggtcttcgcgagtttttggg ccttgaagcgggcccaccgaaaccaaaacccaatcagcagcatcaagatcaagcccgtggtcttgtgctgcctggttataactatctc ggacccggaaacggtctcgatcgaggagagcctgtcaacagggcagacgaggtcgcgcgagagcacgacatctcgtacaacga gcagcttgaggcgggagacaacccctacctcaagtacaaccacgcggacgccgagtttcaggagaagctcgccgacgacacatc cttcgggggaaacctcggaaaggcagtctttcaggccaagaaaagggttctcgaaccttttggcctggttgaagagggtgctaagac ggcccctaccggaaagcggatagacgaccactttccaaaaagaaagaaggctcggaccgaagaggactccaagccttccacctc gtcagacgccgaagctggacccagcggatcccagcagctgcaaatcccagcccaaccagcctcaagtttgggagctgatacaatg tctgcgggaggtggcggcccattgggcgacaataaccaaggtgccgatggagtgggcaatgcctcgggagattggcattgcgatt ccacgtggatgggggacagagtcgtcaccaagtccacccgaacctgggtgctgcccagctacaacaaccaccagtaccgagagat caaaagcggctccgtcgacggaagcaacgccaacgcctactttggatacagcaccccctgggggtactttgactttaaccgcttcca cagccactggagcccccgagactggcaaagactcatcaacaactactggggcttcagaccccggtccctcagagtcaaaatcttca acattcaagtcaaagaggtcacggtgcaggactccaccaccaccatcgccaacaacctcacctccaccgtccaagtgtttacggacg acgactaccagctgccctacgtcgtcggcaacgggaccgagggatgcctgccggccttccctccgcaggtctttacgctgccgcagtacggttacgcgacgctgaaccgcgacaacacagaaaatcccaccgagaggagcagcttcttctgcctagagtactttcccagcaa gatgctgagaacgggcaacaactttgagtttacctacaactttgaggaggtgcccttccactccagcttcgctcccagtcagaacctctt caagctggccaacccgctggtggaccagtacttgtaccgcttcgtgagcacaaataacactggcggagtccagttcaacaagaacct ggccgggagatacgccaacacctacaaaaactggttcccggggcccatgggccgaacccagggctggaacctgggctccgggg tcaaccgcgccagtgtcagcgccttcgccacgaccaataggatggagctcgagggcgcgagttaccaggtgcccccgcagccga acggcatgaccaacaacctccagggcagcaacacctatgccctggagaacactatgatcttcaacagccagccggcgaacccggg caccaccgccacgtacctcgagggcaacatgctcatcaccagcgagagcgagacgcagccggtgaaccgcgtggcgtacaacgt cggcgggcagatggccaccaacaaccagagctccaccactgcccccgcgaccggcacgtacaacctccaggaaatcgtgcccg gcagcgtgtggatggagagggacgtgtacctccaaggacccatctgggccaagatcccagagacgggggcgcactttcacccctc tccggccatgggcggattcggactcaaacacccaccgcccatgatgctcatcaagaacacgcctgtgcccggaaatatcaccagctt ctcggacgtgcccgtcagcagcttcatcacccagtacagcaccgggcaggtcaccgtggagatggagtgggagctcaagaagga aaactccaagaggtggaacccagagatccagtacacaaacaactacaacgacccccagtttgtggactttgccccggacagcaccg gggaatacagaaccaccagacctatcggaacccgataccttacccgacccctttaagctagcagctgatgcatagcatgcggtaccg ggagatgggggaggctaactgaaacacggaaggagacaataccggaaggaacccgcgctatgacggcaataaaaagacagaat aaaacgcacgggtgttgggtcgtttgttcGAGTCATTTAAATACCGGTCTGGGCGAACAAACGATG CTCGCCTTCCAGAAAACCGAGGATGCGAACCACTTCATCCGGGGTCAGCACCAC CGGCAAGCGCCGCGACGGCCGAGGTCTTCCGATCTCCTGAAGCCAGGGCAGATC CGTGCACAGCACCTTGCCGTAGAAGAACAGCAAGGCCGCCAATGCCTGACGATG CGTGGAGACCGAAACCTTGCGCTCGTTCGCCAGCCAGGACAGAAATGCCTCGAC TTCGCTGCTGCCCAAGGTTGCCGGGTGACGCACACCGTGGAAACGGATGAAGGC ACGAACCCAGTTGACATAAGCCTGTTCGGTTCGTAAACTGTAATGCAAGTAGCGT ATGCGCTCACGCAACTGGTCCAGAACCTTGACCGAACGCAGCGGTGGTAACGGC GCAGTGGCGGTTTTCATGGCTTGTTATGACTGTTTTTTTGTACAGTCTATGCCTCG GGCATCCAAGCAGCAAGCGCGTTACGCCGTGGGTCGATGTTTGATGTTATGGAGC AGCAACGATGTTACGCAGCAGCAACGATGTTACGCAGCAGGGCAGTCGCCCTAA AACAAAGTTAGGTGGCTCAAGTATGGGCATCATTCGCACATGTAGGCTCGGCCCT GACCAAGTCAAATCCATGCGGGCTGCTCTTGATCTTTTCGGTCGTGAGTTCGGAG ACGTAGCCACCTACTCCCAACATCAGCCGGACTCCGATTACCTCGGGAACTTGCT CCGTAGTAAGACATTCATCGCGCTTGCTGCCTTCGACCAAGAAGCGGTTGTTGGC GCTCTCGCGGCTTACGTTCTGCCCAAGTTTGAGCAGCCGCGTAGTGAGATCTATAT CTATGATCTCGCAGTCTCCGGCGAGCACCGGAGGCAGGGCATTGCCACCGCGCT CATCAATCTCCTCAAGCATGAGGCCAACGCGCTTGGTGCTTATGTGATCTACGTGC AAGCAGATTACGGTGACGATCCCGCAGTGGCTCTCTATACAAAGTTGGGCATACG GGAAGAAGTGATGCACTTTGATATCGACCCAAGTACCGCCACCTAACAATTCGTT CAAGCCGAGATCGGCTTCCCGGCCGCGGAGTTGTTCGGTAAATTGTCACAACGC CGCGAATATAGTCTTTACCATGCCCTTGGCCACGCCCCTCTTTAATACGACGGGCA ACTTTTTTGTTCCAACCTATCGACGATAAAAACATTGGGAAACGTAGGATTTTTTGCCATGTTTTATGACCCAAATCATAACTATACATGATGCTTCACGATGTTTAATAG GACTTTATTGTCATAGTTTAGATCTATTTTGTTCAGTTTAAGACTTTATTGTCCGCC CACACCCGCTTACGCAGGGCATCCATTTATTACTCAAatcggatcccgggcccgtcgactgcagag gcctgcatgcaagcttggcgtaatcatggtcatagctgtttcctgtgtgaaattgttatccgctcacaattccacacaacatacgagccg gaagcataaagtgtaaagcctggggtgcctaatgagtgagctaactcacattaattgcgttgcgctcactgcccgctttccagtcggga aacctgtcgtgccagctgcattaatgaatcggccaacgcgcggggagaggcggtttgcgtattgggcgctcttccgcttcctcgctca ctgactcgctgcgctcggtcgttcggctgcggcgagcggtatcagctcactcaaaggcggtaatacggttatccacagaatcagggg ataacgcaggaaagaacatgtgagcaaaaggccagcaaaaggccaggaaccgtaaaaaggccgcgttgctggcgtttttccatag gctccgcccccctgacgagcatcacaaaaatcgacgctcaagtcagaggtggcgaaacccgacaggactataaagataccaggc gtttccccctggaagctccctcgtgcgctctcctgttccgaccctgccgcttaccggatacctgtccgcctttctcccttcgggaagcgt ggcgctttctcatagctcacgctgtaggtatctcagttcggtgtaggtcgttcgctccaagctgggctgtgtgcacgaaccccccgttca gcccgaccgctgcgccttatccggtaactatcgtcttgagtccaacccggtaagacacgacttatcgccactggcagcagccactggtaacaggattagcagagcgaggtatgtaggcggtgctacagagttcttgaagtggtggcctaactacggctacactagaagaacagt atttggtatctgcgctctgctgaagccagttaccttcggaaaaagagttggtagctcttgatccggcaaacaaaccaccgctggtagcg gtggtttttttgtttgcaagcagcagattacgcgcagaaaaaaaggatctcaagaagatcctttgatcttttctacggggtctgacgctca gtggaacgaaaactcacgttaagggattttggtcatgagattatcaaaaaggatcttcacctagatccttttaaattaaaaatgaagtttta aatcaatctaaagtatatatgagtaaacttggtctgacagttaccaatgcttaatcagtgaggcacctatctcagcgatctgtctatttcgtt catccatagttgcctgactccccgtcgtgtagataactacgatacgggagggcttaccatctggccccagtgctgcaatgataccgcg agacccacgctcaccggctccagatttatcagcaataaaccagccagccggaagggccgagcgcagaagtggtcctgcaactttat ccgcctccatccagtctattaattgttgccgggaagctagagtaagtagttcgccagttaatagtttgcgcaacgttgttgccattgctac aggcatcgtggtgtcacgctcgtcgtttggtatggcttcattcagctccggttcccaacgatcaaggcgagttacatgatcccccatgtt gtgcaaaaaagcggttagctccttcggtcctccgatcgttgtcagaagtaagttggccgcagtgttatcactcatggttatggcagcact gcataattctcttactgtcatgccatccgtaagatgcttttctgtgactggtgagtactcaaccaagtcattctgagaatagtgtatgcggc gaccgagttgctcttgcccggcgtcaatacgggataataccgcgccacatagcagaactttaaaagtgctcatcattggaaaacgttct tcggggcgaaaactctcaaggatcttaccgctgttgagatccagttcgatgtaacccactcgtgcacccaactgatcttcagcatctttt actttcaccagcgtttctgggtgagcaaaaacaggaaggcaaaatgccgcaaaaaagggaataagggcgacacggaaatgttgaat actcatactcttcctttttcaatattattgaagcatttatcagggttattgtctcatgagcggatacatatttgaatgtatttagaaaaataaaca aataggggttccgcgcacatttccccgaaaagtgccacctgacgtctaagaaaccattattatcatgacattaacctataaaaataggc gtatcacgaggccctttcgtc pFBacX-AAVRep2ACap5_44AE Syn21 (SEQ ID NO: 41) tcgcgcgtttcggtgatgacggtgaaaacctctgacacatgcagctcccggagacggtcacagcttgtctgtaagcggatgccggga gcagacaagcccgtcagggcgcgtcagcgggtgttggcgggtgtcggggctggcttaactatgcggcatcagagcagattgtact gagagtgcaccatatgcggtgtgaaataccgcacagatgcgtaaggagaaaataccgcatcaggcgccattcgccattcaggctgc gcaactgttgggaagggcgatcggtgcgggcctcttcgctattacgccagctggcgaaagggggatgtgctgcaaggcgattaagt tgggtaacgccagggttttcccagtcacgacgttgtaaaacgacggccagtgaattcgagctcggtacctcgcgaatgcatctagat GATTAAAAACATAACAGGAAGAAAAATGCCCCGCTGTGGGCGGACAAAATAGTT GGGAACTGGGAGGGGTGGAAATGGAGTTTTTAAGGATTATTTAGGGAAGAGTGA CAAAATAGATGGGAACTGGGTGTAGCGTCGTAAGCTAATACGAAAATTAAAAATG ACAAAATAGTTTGGAACTAGATTTCACTTATCTGGTTcggatctgggtccccctaggctcaagcagt gatcagatccagacatgataagatacattgatgagtttggacaaaccacaactagaatgcagtgaaaaaaatgctttatttgtgaaattt gtgatgctattgctttatttgtaaccattataagctgcaataaacaagttaacaacaacaattgcattcattttatgtttcaggttcaggggga ggtgtgggaggttttttaaagcaagtaaaacctctacaaatgtggtatggctgattatgatcctctagtacttctcgacaagcttgtcgag actgcaggctctagagtcgacctgcaggcatgcaagcttgattcctcgagtttattgttcaaagatgcagtcatccaaatccacattgac cagatcgcaggcagtgcaagcgtctggcacctttcccatgatatgatgaatgtagcacagtttctgatacgcctttttgacgacagaaa cgggttgagattctgacacgggaaagcactctaaacagtctttctgtccgtgagtgaagcagatatttgaattctgattcattctctcgcat tgtctgcagggaaacagcatcagattcatgcccacgtgacgagaacatttgttttggtacctgtctgcgtagttgatcgaagcttccgcg tctgacgtcgatggctgcgcaactgactcgcgcacccgtttgggctcacttatatctgcgtcactgggggcgggtcttttcttggctcca ccctttttgacgtagaattcatgctccacctcaaccacgtgatcctttgcccaccggaaaaagtctttgacttcctgcttggtgaccttccc aaagtcatgatccagacggcgggtgagttcaaatttgaacatccggtcttgcaacggctgctggtgttcgaaggtcgttgagttcccgt caatcacggcgcacatgttggtgttggaggtgacgatcacgggagtcgggtctatctgggccgaggacttgcatttctggtccacgc gcaccttgcttcctccgagaatggctttggccgactccacgaccttggcggtcatcttcccctcctcccaccagatcaccatcttgtcga cacagtcgttgaagggaaagttctcattggtccagtttacgcacccgtagaagggcacagtgtgggctatggcctccgcgatgttggt cttcccggtagttgcaggcccaaacagccagatggtgttcctcttgccgaactttttcgtggcccatcccagaaagacggaagccgca tattggggatcgtacccgtttagttccaaaattttataaatccgattgctggaaatgtcctccacgggctgctggcccaccaggtagtcg ggggcggttttagtcaggctcataatctttcccgcattgtccaaggcagccttgatttgggaccgcgagttggaggccgcattgaagg agatgtatgaAgcctggtcctcctggatccactgcttctccgaggtaatccccttgtccacgagccacccgaccagctccatgtacct ggctgaagtttttgatctgatcaccggcgcgtcagaattgggattctgattctctttgttctgctcctgcgtctgcgacacgtgcgtcagat gctgcgccaccaaccgtttacgctccgtgagattcaaacaggcgcttaaatactgttctaaattagtccacgcccactggagctcagg ctgggttttggggagcaagtaattggggatgtagcactcgtccaccaccttgttcccgcctccggcgccgtttctggtctttgtgaccgcgaaccagtttggcaaagtcggctcgatcccgcggtaaattctctgaatcagtttttcgcgaatctgactcaggaaacgtcccaaaacta aggatttcaccccggtggtttccacgagcacgtgtaagtggaagtagctctctcccttctcaaattgcacaaagaaaagggcctccgg ggccttactcacacggcgccactccgtcagaaagtcgcgctgcagcttctcggccacggtcaggggtgcctgctcaatcagattcag atccaagtcagaatctggcggcaactcccactccttctcggccacccagttcacaaagctgtcagaaatgccgggcagatgctcgtc aaggtcgctggggaccttaatcacaatctcgtaaaaccccgccagggcggcagatccgcgcccgatggtGCGGCCGCacg gtatgaataatccggaatatttataggtttttttattacaaaactgttacgaaaacagtaaaatacttatttatttgcgagatggttatcatttta attatctccatgatctattaatattcACGCGTcggagtatacggacctttaattcaacccaacacaatatattatagttaaataagaatt attatcaaatcatttgtatattaattaaaatactatactgtaaattacattttatttacaatcaatactagtaaaaggtaggttcaaccactgatg cctaggcacaccgaaacgactaaccctaattcttatcctttacttcaggcgcgcccggcttaagcgtacgaacttaaaaaaaaaaatca aaTtTTTTatgtcttttgttgatcaccctccagattggttggaagaagttggtgaaggtcttcgcgagtttttgggccttgaagcgggc ccaccgaaaccaaaacccaatcagcagcatcaagatcaagcccgtggtcttgtgctgcctggttataactatctcggacccggaaac ggtctcgatcgaggagagcctgtcaacagggcagacgaggtcgcgcgagagcacgacatctcgtacaacgagcagcttgaggcg ggagacaacccctacctcaagtacaaccacgcggacgccgagtttcaggagaagctcgccgacgacacatccttcgggggaaac ctcggaaaggcagtctttcaggccaagaaaagggttctcgaaccttttggcctggttgaagagggtgctaagacggcccctaccgga aagcggatagacgaccactttccaaaaagaaagaaggctcggaccgaagaggactccaagccttccacctcgtcagacgccgaa gctggacccagcggatcccagcagctgcaaatcccagcccaaccagcctcaagtttgggagctgatacaatgtctgcgggaggtg gcggcccattgggcgacaataaccaaggtgccgatggagtgggcaatgcctcgggagattggcattgcgattccacgtggatggg ggacagagtcgtcaccaagtccacccgaacctgggtgctgcccagctacaacaaccaccagtaccgagagatcaaaagcggctcc gtcgacggaagcaacgccaacgcctactttggatacagcaccccctgggggtactttgactttaaccgcttccacagccactggagc ccccgagactggcaaagactcatcaacaactactggggcttcagaccccggtccctcagagtcaaaatcttcaacattcaagtcaaa gaggtcacggtgcaggactccaccaccaccatcgccaacaacctcacctccaccgtccaagtgtttacggacgacgactaccagct gccctacgtcgtcggcaacgggaccgagggatgcctgccggccttccctccgcaggtctttacgctgccgcagtacggttacgcga cgctgaaccgcgacaacacagaaaatcccaccgagaggagcagcttcttctgcctagagtactttcccagcaagatgctgagaacg ggcaacaactttgagtttacctacaactttgaggaggtgcccttccactccagcttcgctcccagtcagaacctcttcaagctggccaa cccgctggtggaccagtacttgtaccgcttcgtgagcacaaataacactggcggagtccagttcaacaagaacctggccgggagat acgccaacacctacaaaaactggttcccggggcccatgggccgaacccagggctggaacctgggctccggggtcaaccgcgcca gtgtcagcgccttcgccacgaccaataggatggagctcgagggcgcgagttaccaggtgcccccgcagccgaacggcatgacca acaacctccagggcagcaacacctatgccctggagaacactatgatcttcaacagccagccggcgaacccgggcaccaccgcca cgtacctcgagggcaacatgctcatcaccagcgagagcgagacgcagccggtgaaccgcgtggcgtacaacgtcggcgggcag atggccaccaacaaccagagctccaccactgcccccgcgaccggcacgtacaacctccaggaaatcgtgcccggcagcgtgtgg atggagagggacgtgtacctccaaggacccatctgggccaagatcccagagacgggggcgcactttcacccctctccggccatgg gcggattcggactcaaacacccaccgcccatgatgctcatcaagaacacgcctgtgcccggaaatatcaccagcttctcggacgtgc ccgtcagcagcttcatcacccagtacagcaccgggcaggtcaccgtggagatggagtgggagctcaagaaggaaaactccaaga ggtggaacccagagatccagtacacaaacaactacaacgacccccagtttgtggactttgccccggacagcaccggggaatacag aaccaccagacctatcggaacccgataccttacccgacccctttaagctagcagctgatgcatagcatgcggtaccgggagatggg ggaggctaactgaaacacggaaggagacaataccggaaggaacccgcgctatgacggcaataaaaagacagaataaaacgcac gggtgttgggtcgtttgttcGAGTCATTTAAATACCGGTCTGGGCGAACAAACGATGCTCGCC TTCCAGAAAACCGAGGATGCGAACCACTTCATCCGGGGTCAGCACCACCGGCAA GCGCCGCGACGGCCGAGGTCTTCCGATCTCCTGAAGCCAGGGCAGATCCGTGCA CAGCACCTTGCCGTAGAAGAACAGCAAGGCCGCCAATGCCTGACGATGCGTGGA GACCGAAACCTTGCGCTCGTTCGCCAGCCAGGACAGAAATGCCTCGACTTCGCT GCTGCCCAAGGTTGCCGGGTGACGCACACCGTGGAAACGGATGAAGGCACGAA CCCAGTTGACATAAGCCTGTTCGGTTCGTAAACTGTAATGCAAGTAGCGTATGCG CTCACGCAACTGGTCCAGAACCTTGACCGAACGCAGCGGTGGTAACGGCGCAGT GGCGGTTTTCATGGCTTGTTATGACTGTTTTTTTGTACAGTCTATGCCTCGGGCAT CCAAGCAGCAAGCGCGTTACGCCGTGGGTCGATGTTTGATGTTATGGAGCAGCA ACGATGTTACGCAGCAGCAACGATGTTACGCAGCAGGGCAGTCGCCCTAAAACA AAGTTAGGTGGCTCAAGTATGGGCATCATTCGCACATGTAGGCTCGGCCCTGACC AAGTCAAATCCATGCGGGCTGCTCTTGATCTTTTCGGTCGTGAGTTCGGAGACGTAGCCACCTACTCCCAACATCAGCCGGACTCCGATTACCTCGGGAACTTGCTCCGT AGTAAGACATTCATCGCGCTTGCTGCCTTCGACCAAGAAGCGGTTGTTGGCGCTC TCGCGGCTTACGTTCTGCCCAAGTTTGAGCAGCCGCGTAGTGAGATCTATATCTAT GATCTCGCAGTCTCCGGCGAGCACCGGAGGCAGGGCATTGCCACCGCGCTCATC AATCTCCTCAAGCATGAGGCCAACGCGCTTGGTGCTTATGTGATCTACGTGCAAG CAGATTACGGTGACGATCCCGCAGTGGCTCTCTATACAAAGTTGGGCATACGGGA AGAAGTGATGCACTTTGATATCGACCCAAGTACCGCCACCTAACAATTCGTTCAA GCCGAGATCGGCTTCCCGGCCGCGGAGTTGTTCGGTAAATTGTCACAACGCCGC GAATATAGTCTTTACCATGCCCTTGGCCACGCCCCTCTTTAATACGACGGGCAATT TGCACTTCAGAAAATGAAGAGTTTGCTTTAGCCATAACAAAAGTCCAGTATGCTT TTTCACAGCATAACTGGACTGATTTCAGTTTACAACTATTCTGTCTAGTTTAAGAC TTTATTGTCATAGTTTAGATCTATTTTGTTCAGTTTAAGACTTTATTGTCCGCCCAC ACCCGCTTACGCAGGGCATCCATTTATTACTCAAatcggatcccgggcccgtcgactgcagaggcct gcatgcaagcttggcgtaatcatggtcatagctgtttcctgtgtgaaattgttatccgctcacaattccacacaacatacgagccggaag cataaagtgtaaagcctggggtgcctaatgagtgagctaactcacattaattgcgttgcgctcactgcccgctttccagtcgggaaacc tgtcgtgccagctgcattaatgaatcggccaacgcgcggggagaggcggtttgcgtattgggcgctcttccgcttcctcgctcactga ctcgctgcgctcggtcgttcggctgcggcgagcggtatcagctcactcaaaggcggtaatacggttatccacagaatcaggggataa cgcaggaaagaacatgtgagcaaaaggccagcaaaaggccaggaaccgtaaaaaggccgcgttgctggcgtttttccataggctc cgcccccctgacgagcatcacaaaaatcgacgctcaagtcagaggtggcgaaacccgacaggactataaagataccaggcgtttc cccctggaagctccctcgtgcgctctcctgttccgaccctgccgcttaccggatacctgtccgcctttctcccttcgggaagcgtggcg ctttctcatagctcacgctgtaggtatctcagttcggtgtaggtcgttcgctccaagctgggctgtgtgcacgaaccccccgttcagccc gaccgctgcgccttatccggtaactatcgtcttgagtccaacccggtaagacacgacttatcgccactggcagcagccactggtaaca ggattagcagagcgaggtatgtaggcggtgctacagagttcttgaagtggtggcctaactacggctacactagaagaacagtatttg gtatctgcgctctgctgaagccagttaccttcggaaaaagagttggtagctcttgatccggcaaacaaaccaccgctggtagcggtgg tttttttgtttgcaagcagcagattacgcgcagaaaaaaaggatctcaagaagatcctttgatcttttctacggggtctgacgctcagtgg aacgaaaactcacgttaagggattttggtcatgagattatcaaaaaggatcttcacctagatccttttaaattaaaaatgaagttttaaatc aatctaaagtatatatgagtaaacttggtctgacagttaccaatgcttaatcagtgaggcacctatctcagcgatctgtctatttcgltcatc catagttgcctgactccccgtcgtgtagataactacgatacgggagggcttaccatctggccccagtgctgcaatgataccgcgagac ccacgctcaccggctccagattlatcagcaataaaccagccagccggaagggccgagcgcagaagtggtcctgcaactttatccgc ctccatccagtctattaattgttgccgggaagctagagtaagtagttcgccagttaatagtttgcgcaacgttgttgccattgctacaggc atcgtggtgtcacgctcgtcgtttggtatggcttcattcagctccggttcccaacgatcaaggcgagttacatgatcccccatgttgtgca aaaaagcggttagctccttcggtcctccgatcgttgtcagaagtaagttggccgcagtgttatcactcatggttatggcagcactgcata attctcttactgtcatgccatccgtaagatgcttttctgtgactggtgagtactcaaccaagtcattctgagaatagtgtatgcggcgaccg agttgctcttgcccggcgtcaatacgggataataccgcgccacatagcagaactttaaaagtgctcatcattggaaaacgttcttcggg gcgaaaactctcaaggatcttaccgctgttgagatccagttcgatgtaacccactcgtgcacccaactgatcttcagcatcttttactttca ccagcgtttctgggtgagcaaaaacaggaaggcaaaatgccgcaaaaaagggaataagggcgacacggaaatgttgaatactcat actcttcctttttcaatattattgaagcatttatcagggttattgtctcatgagcggatacatatttgaatgtatttagaaaaataaacaaatag gggttccgcgcacatttccccgaaaagtgccacctgacgtctaagaaaccattattatcatgacattaacctataaaaataggcgtatca cgaggccctttcgtc pFBacX-AAVRep2ACap5_40CE L21 (SEQ ID NO: 42) tcgcgcgtttcggtgatgacggtgaaaacctctgacacatgcagctcccggagacggtcacagcttgtctgtaagcggatgccggga gcagacaagcccgtcagggcgcgtcagcgggtgttggcgggtgtcggggctggcttaactatgcggcatcagagcagattgtact gagagtgcaccatatgcggtgtgaaataccgcacagatgcgtaaggagaaaataccgcatcaggcgccattcgccattcaggctgc gcaactgttgggaagggcgatcggtgcgggcctcttcgctattacgccagctggcgaaagggggatgtgctgcaaggcgattaagt tgggtaacgccagggttttcccagtcacgacgttgtaaaacgacggccagtgaattcgagctcggtacctcgcgaatgcatctagatGATTAAAAACATAACAGGAAGAAAAATGCCCCGCTGTGGGCGGACAAAATAGTT GGGAACTGGGAGGGGTGGAAATGGAGTTTTTAAGGATTATTTAGGGAAGAGTGA CAAAATAGATGGGAACTGGGTGTAGCGTCGTAAGCTAATACGAAAATTAAAAATG ACAAAATAGTTTGGAACTAGATTTCACTTATCTGGTTcggatctgggtccccctaggctcaagcagt gatcagatccagacatgataagatacattgatgagtttggacaaaccacaactagaatgcagtgaaaaaaatgctttatttgtgaaattt gtgatgctattgctttatttgtaaccattataagctgcaataaacaagttaacaacaacaattgcattcattttatgtttcaggttcaggggga ggtgtgggaggttttttaaagcaagtaaaacctctacaaatgtggtatggctgattatgatcctctagtacttctcgacaagcttgtcgag actgcaggctctagagtcgacctgcaggcatgcaagcttgattcctcgagtttattgttcaaagatgcagtcatccaaatccacattgac cagatcgcaggcagtgcaagcgtctggcacctttcccatgatatgatgaatgtagcacagtttctgatacgcctttttgacgacagaaa cgggttgagattctgacacgggaaagcactctaaacagtctttctgtccgtgagtgaagcagatatttgaattctgattcattctctcgcat tgtctgcagggaaacagcatcagattcatgcccacgtgacgagaacatttgttttggtacctgtctgcgtagttgatcgaagcttccgcg tctgacgtcgatggctgcgcaactgactcgcgcacccgtttgggctcacttatatctgcgtcactgggggcgggtcttttcttggctcca ccctttttgacgtagaattcatgctccacctcaaccacgtgatcctttgcccaccggaaaaagtctttgacttcctgcttggtgaccttccc aaagtcatgatccagacggcgggtgagttcaaatttgaacatccggtcttgcaacggctgctggtgttcgaaggtcgttgagttcccgt caatcacggcgcacatgttggtgttggaggtgacgatcacgggagtcgggtctatctgggccgaggacttgcatttctggtccacgc gcaccttgcttcctccgagaatggctttggccgactccacgaccttggcggtcatcttcccctcctcccaccagatcaccatcttgtcga cacagtcgttgaagggaaagttctcattggtccagtttacgcacccgtagaagggcacagtgtgggctatggcctccgcgatgttggt cttcccggtagttgcaggcccaaacagccagatggtgttcctcttgccgaactttttcgtggcccatcccagaaagacggaagccgca tattggggatcgtacccgtttagttccaaaattttataaatccgattgctggaaatgtcctccacgggctgctggcccaccaggtagtcg ggggcggttttagtcaggctcataatctttcccgcattgtccaaggcagccttgatttgggaccgcgagttggaggccgcattgaagg agatgtatgaAgcctggtcctcctggatccactgcttctccgaggtaatccccttgtccacgagccacccgaccagctccatgtacct ggctgaagtttttgatctgatcaccggcgcgtcagaattgggattctgattctctttgttctgctcctgcgtctgcgacacgtgcgtcagat gctgcgccaccaaccgtttacgctccgtgagattcaaacaggcgcttaaatactgttctaaattagtccacgcccactggagctcagg ctgggttttggggagcaagtaattggggatgtagcactcgtccaccaccttgttcccgcctccggcgccgtttctggtctttgtgaccgc gaaccagtttggcaaagtcggctcgatcccgcggtaaattctctgaatcagtttttcgcgaatctgactcaggaaacgtcccaaaacta aggatttcaccccggtggtttccacgagcacgtgtaagtggaagtagctctctcccttctcaaattgcacaaagaaaagggcctccgg ggccttactcacacggcgccactccgtcagaaagtcgcgctgcagcttclcggccacggtcaggggtgcctgctcaatcagattcag atccaagtcagaatctggcggcaactcccactccttctcggccacccagttcacaaagctgtcagaaatgccgggcagatgctcgtc aaggtcgctggggaccttaatcacaatctcgtaaaaccccgccagggcggcagatccgcgcccgatggtGCGGCCGCacg gtatgaataatccggaatatttataggtttttttattacaaaactgttacgaaaacagtaaaatacttatttatttgcgagatggttatcatttta attatctccatgatctattaatattcACGCGTcggagtatacggacctttaattcaacccaacacaatatattatagttaaataagaatt attatcaaatcatttgtatattaattaaaatactatactgtaaattacattttatttacaatcaatactagtaaaaggtaggttcaaccactgatg cctaggcacaccgaaacgactaaccctaattcttatcctttacttcaggcgcgcccggcttaagcgtacgAACTCCTAAAA AACCGCCACCtgTGTTTTatgtcttttgttgatcaccctccagattggttggaagaagttggtgaaggtcttcgcgagttttt gggccttgaagcgggcccaccgaaaccaaaacccaatcagcagcatcaagatcaagcccgtggtcttgtgctgcctggttataacta tctcggacccggaaacggtctcgatcgaggagagcctgtcaacagggcagacgaggtcgcgcgagagcacgacatctcgtacaa cgagcagcttgaggcgggagacaacccctacctcaagtacaaccacgcggacgccgagtttcaggagaagctcgccgacgacac atccttcgggggaaacctcggaaaggcagtctttcaggccaagaaaagggttctcgaaccttttggcctggttgaagagggtgctaa gacggcccctaccggaaagcggatagacgaccactttccaaaaagaaagaaggctcggaccgaagaggactccaagccttccac ctcgtcagacgccgaagctggacccagcggatcccagcagctgcaaatcccagcccaaccagcctcaagtttgggagctgataca atgtctgcgggaggtggcggcccattgggcgacaataaccaaggtgccgatggagtgggcaatgcctcgggagattggcattgcg attccacgtggatgggggacagagtcgtcaccaagtccacccgaacctgggtgctgcccagctacaacaaccaccagtaccgaga gatcaaaagcggctccgtcgacggaagcaacgccaacgcctactttggatacagcaccccctgggggtactttgactttaaccgctt ccacagccactggagcccccgagactggcaaagactcatcaacaactactggggcttcagaccccggtccctcagagtcaaaatct tcaacattcaagtcaaagaggtcacggtgcaggactccaccaccaccatcgccaacaacctcacctccaccgtccaagtgtttacgg acgacgactaccagctgccctacgtcgtcggcaacgggaccgagggatgcctgccggccttccctccgcaggtctttacgctgccg cagtacggttacgcgacgctgaaccgcgacaacacagaaaatcccaccgagaggagcagcttcttctgcctagagtactttcccag caagatgctgagaacgggcaacaactttgagtttacctacaactttgaggaggtgcccttccactccagcttcgctcccagtcagaac ctcttcaagctggccaacccgctggtggaccagtacttgtaccgcttcgtgagcacaaataacactggcggagtccagttcaacaagaacctggccgggagatacgccaacacctacaaaaactggttcccggggcccatgggccgaacccagggctggaacctgggctcc ggggtcaaccgcgccagtgtcagcgccttcgccacgaccaataggatggagctcgagggcgcgagttaccaggtgcccccgcag ccgaacggcatgaccaacaacctccagggcagcaacacctatgccctggagaacactatgatcttcaacagccagccggcgaacc cgggcaccaccgccacgtacctcgagggcaacatgctcatcaccagcgagagcgagacgcagccggtgaaccgcgtggcgtac aacgtcggcgggcagatggccaccaacaaccagagctccaccactgcccccgcgaccggcacgtacaacctccaggaaatcgtg cccggcagcgtgtggatggagagggacgtgtacctccaaggacccatctgggccaagatcccagagacgggggcgcactttcac ccctctccggccatgggcggattcggactcaaacacccaccgcccatgatgctcatcaagaacacgcctgtgcccggaaatatcac cagcttctcggacgtgcccgtcagcagcttcatcacccagtacagcaccgggcaggtcaccgtggagatggagtgggagctcaag aaggaaaactccaagaggtggaacccagagatccagtacacaaacaactacaacgacccccagtttgtggactttgccccggaca gcaccggggaatacagaaccaccagacctatcggaacccgataccttacccgacccctttaagctagcagctgatgcatagcatgc ggtaccgggagatgggggaggctaactgaaacacggaaggagacaataccggaaggaacccgcgctatgacggcaataaaaag acagaataaaacgcacgggtgttgggtcgtttgttcGAGTCATTTAAATACCGGTCTGGGCGAACAAA CGATGCTCGCCTTCCAGAAAACCGAGGATGCGAACCACTTCATCCGGGGTCAGC ACCACCGGCAAGCGCCGCGACGGCCGAGGTCTTCCGATCTCCTGAAGCCAGGGC AGATCCGTGCACAGCACCTTGCCGTAGAAGAACAGCAAGGCCGCCAATGCCTGA CGATGCGTGGAGACCGAAACCTTGCGCTCGTTCGCCAGCCAGGACAGAAATGCC TCGACTTCGCTGCTGCCCAAGGTTGCCGGGTGACGCACACCGTGGAAACGGATG AAGGCACGAACCCAGTTGACATAAGCCTGTTCGGTTCGTAAACTGTAATGCAAGT AGCGTATGCGCTCACGCAACTGGTCCAGAACCTTGACCGAACGCAGCGGTGGTA ACGGCGCAGTGGCGGTTTTCATGGCTTGTTATGACTGTTTTTTTGTACAGTCTATG CCTCGGGCATCCAAGCAGCAAGCGCGTTACGCCGTGGGTCGATGTTTGATGTTAT GGAGCAGCAACGATGTTACGCAGCAGCAACGATGTTACGCAGCAGGGCAGTCGC CCTAAAACAAAGTTAGGTGGCTCAAGTATGGGCATCATTCGCACATGTAGGCTCG GCCCTGACCAAGTCAAATCCATGCGGGCTGCTCTTGATCTTTTCGGTCGTGAGTT CGGAGACGTAGCCACCTACTCCCAACATCAGCCGGACTCCGATTACCTCGGGAA CTTGCTCCGTAGTAAGACATTCATCGCGCTTGCTGCCTTCGACCAAGAAGCGGTT GTTGGCGCTCTCGCGGCTTACGTTCTGCCCAAGTTTGAGCAGCCGCGTAGTGAGA TCTATATCTATGATCTCGCAGTCTCCGGCGAGCACCGGAGGCAGGGCATTGCCAC CGCGCTCATCAATCTCCTCAAGCATGAGGCCAACGCGCTTGGTGCTTATGTGATCT ACGTGCAAGCAGATTACGGTGACGATCCCGCAGTGGCTCTCTATACAAAGTTGGG CATACGGGAAGAAGTGATGCACTTTGATATCGACCCAAGTACCGCCACCTAACAA TTCGTTCAAGCCGAGATCGGCTTCCCGGCCGCGGAGTTGTTCGGTAAATTGTCAC AACGCCGCGAATATAGTCTTTACCATGCCCTTGGCCACGCCCCTCTTTAATACGAC GGGCAATTTGCACTTCAGAAAATGAAGAGTTTGCTTTAGCCATAACAAAAGTCCA GTATGCTTTTTCACAGCATAACTGGACTGATTTCAGTTTACAACTATTCTGTCTAGT TTAAGACTTTATTGTCATAGTTTAGATCTATTTTGTTCAGTTTAAGACTTTATTGTCC GCCCACACCCGCTTACGCAGGGCATCCATTTATTACTCAAatcggatcccgggcccgtcgactg cagaggcctgcatgcaagcttggcgtaatcatggtcatagctgtttcctgtgtgaaattgttatccgctcacaattccacacaacatacg agccggaagcataaagtgtaaagcctggggtgcctaatgagtgagctaactcacattaattgcgttgcgctcactgcccgctttccagt cgggaaacctgtcgtgccagctgcattaatgaatcggccaacgcgcggggagaggcggtttgcgtattgggcgctcttccgcttcct cgctcactgactcgctgcgctcggtcgttcggctgcggcgagcggtatcagctcactcaaaggcggtaatacggttatccacagaat caggggataacgcaggaaagaacatgtgagcaaaaggccagcaaaaggccaggaaccgtaaaaaggccgcgttgctggcgtttt tccataggctccgcccccctgacgagcatcacaaaaatcgacgctcaagtcagaggtggcgaaacccgacaggactataaagata ccaggcgtttccccctggaagctccctcgtgcgctctcctgttccgaccctgccgcttaccggatacctgtccgcctttctcccttcggg aagcgtggcgctttctcatagctcacgctgtaggtatctcagttcggtgtaggtcgttcgctccaagctgggctgtgtgcacgaacccc ccgttcagcccgaccgctgcgccttatccggtaactatcgtcttgagtccaacccggtaagacacgacttatcgccactggcagcagc cactggtaacaggattagcagagcgaggtatgtaggcggtgctacagagttcttgaagtggtggcctaactacggctacactagaag aacagtatttggtatctgcgctctgctgaagccagttaccttcggaaaaagagttggtagctcttgatccggcaaacaaaccaccgctg gtagcggtggtttttttgtttgcaagcagcagattacgcgcagaaaaaaaggatctcaagaagatcctttgatcttttctacggggtctgacgctcagtggaacgaaaactcacgttaagggattttggtcatgagattatcaaaaaggatcttcacctagatccttttaaattaaaaatga agttttaaatcaatctaaagtatatatgagtaaacttggtctgacagttaccaatgcttaatcagtgaggcacctatctcagcgatctgtcta tttcgttcatccatagttgcctgactccccgtcgtgtagataactacgatacgggagggcttaccatctggccccagtgctgcaatgata ccgcgagacccacgctcaccggctccagatttatcagcaataaaccagccagccggaagggccgagcgcagaagtggtcctgca actttatccgcctccatccagtctattaattgttgccgggaagctagagtaagtagttcgccagttaatagtttgcgcaacgttgttgccat tgctacaggcatcgtggtgtcacgctcgtcgtttggtatggcttcattcagctccggttcccaacgatcaaggcgagttacatgatcccc catgttgtgcaaaaaagcggttagctccttcggtcctccgatcgttgtcagaagtaagttggccgcagtgttatcactcatggttatggc agcactgcataattctcttactgtcatgccatccgtaagatgcttttctgtgactggtgagtactcaaccaagtcattctgagaatagtgtat gcggcgaccgagttgctcttgcccggcgtcaatacgggataataccgcgccacatagcagaactttaaaagtgctcatcattggaaa acgttcttcggggcgaaaactctcaaggatcttaccgctgttgagatccagttcgatgtaacccactcgtgcacccaactgatcttcagc atcttttactttcaccagcgtttctgggtgagcaaaaacaggaaggcaaaatgccgcaaaaaagggaataagggcgacacggaaat gttgaatactcatactcttcctttttcaatattattgaagcatttatcagggttattgtctcatgagcggatacatatttgaatgtatttagaaaa ataaacaaataggggttccgcgcacatttccccgaaaagtgccacctgacgtctaagaaaccattattatcatgacattaacctataaaa ataggcgtatcacgaggccctttcgtc pFBacX-AAVRep2ACap5_40CE Syn21 (SEQ ID NO: 43) tcgcgcgtttcggtgatgacggtgaaaacctctgacacatgcagctcccggagacggtcacagcttgtctgtaagcggatgccggga gcagacaagcccgtcagggcgcgtcagcgggtgttggcgggtgtcggggctggcttaactatgcggcatcagagcagattgtact gagagtgcaccatatgcggtgtgaaataccgcacagatgcgtaaggagaaaataccgcatcaggcgccattcgccattcaggctgc gcaactgttgggaagggcgatcggtgcgggcctcttcgctattacgccagctggcgaaagggggatgtgctgcaaggcgattaagt tgggtaacgccagggttttcccagtcacgacgttgtaaaacgacggccagtgaattcgagctcggtacctcgcgaatgcatctagat GATTAAAAACATAACAGGAAGAAAAATGCCCCGCTGTGGGCGGACAAAATAGTT GGGAACTGGGAGGGGTGGAAATGGAGTTTTTAAGGATTATTTAGGGAAGAGTGA CAAAATAGATGGGAACTGGGTGTAGCGTCGTAAGCTAATACGAAAATTAAAAATG ACAAAATAGTTTGGAACTAGATTTCACTTATCTGGTTcggatctgggtccccctaggctcaagcagt gatcagatccagacatgataagatacattgatgagtttggacaaaccacaactagaatgcagtgaaaaaaatgctttatttgtgaaattt gtgatgctattgctttatttgtaaccattataagctgcaataaacaagttaacaacaacaattgcattcattttatgtttcaggttcaggggga ggtgtgggaggttttttaaagcaagtaaaacctctacaaatgtggtatggctgattatgatcctctagtacttctcgacaagcttgtcgag actgcaggctctagagtcgacctgcaggcatgcaagcttgattcctcgagtttattgttcaaagatgcagtcatccaaatccacattgac cagatcgcaggcagtgcaagcgtctggcacctttcccatgatatgatgaatgtagcacagtttctgatacgcctttttgacgacagaaa cgggttgagattctgacacgggaaagcactctaaacagtctttctgtccgtgagtgaagcagatatttgaattctgattcattctctcgcat tgtctgcagggaaacagcatcagattcatgcccacgtgacgagaacatttgttttggtacctgtctgcgtagttgatcgaagcttccgcg tctgacgtcgatggctgcgcaactgactcgcgcacccgtttgggctcacttatatctgcgtcactgggggcgggtcttttcttggctcca ccctttttgacgtagaattcatgctccacctcaaccacgtgatcctttgcccaccggaaaaagtctttgacttcctgcttggtgaccttccc aaagtcatgatccagacggcgggtgagttcaaatttgaacatccggtcttgcaacggctgctggtgttcgaaggtcgttgagttcccgt caatcacggcgcacatgttggtgttggaggtgacgatcacgggagtcgggtctatctgggccgaggacttgcatttctggtccacgc gcaccttgcttcctccgagaatggctttggccgactccacgaccttggcggtcatcttcccctcctcccaccagatcaccatcttgtcga cacagtcgttgaagggaaagttctcattggtccagtttacgcacccgtagaagggcacagtgtgggctatggcctccgcgatgttggt cttcccggtagttgcaggcccaaacagccagatggtgttcctcttgccgaactttttcgtggcccatcccagaaagacggaagccgca tattggggatcgtacccgtttagttccaaaattttataaatccgattgctggaaatgtcctccacgggctgctggcccaccaggtagtcg ggggcggttttagtcaggctcataatctttcccgcattgtccaaggcagccttgatttgggaccgcgagttggaggccgcattgaagg agatgtatgaAgcctggtcctcctggatccactgcttctccgaggtaatccccttgtccacgagccacccgaccagctccatgtacct ggctgaagtttttgatctgatcaccggcgcgtcagaattgggattctgattctctttgttctgctcctgcgtctgcgacacgtgcgtcagat gctgcgccaccaaccgtttacgctccgtgagattcaaacaggcgcttaaatactgttctaaattagtccacgcccactggagctcagg ctgggttttggggagcaagtaattggggatgtagcactcgtccaccaccttgttcccgcctccggcgccgtttctggtctttgtgaccgc gaaccagtttggcaaagtcggctcgatcccgcggtaaattctctgaatcagtttttcgcgaatctgactcaggaaacgtcccaaaactaaggatttcaccccggtggtttccacgagcacgtgtaagtggaagtagctctctcccttctcaaattgcacaaagaaaagggcctccgg ggccttactcacacggcgccactccgtcagaaagtcgcgctgcagcttctcggccacggtcaggggtgcctgctcaatcagattcag atccaagtcagaatctggcggcaactcccactccttctcggccacccagttcacaaagctgtcagaaatgccgggcagatgctcgtc aaggtcgctggggaccttaatcacaatctcgtaaaaccccgccagggcggcagatccgcgcccgatggtGCGGCCGCacg gtatgaataatccggaatatttataggtttttttattacaaaactgttacgaaaacagtaaaatacttatttatttgcgagatggttatcatttta attatctccatgatctattaatattcACGCGTcggagtatacggacctttaattcaacccaacacaatatattatagttaaataagaatt attatcaaatcatttgtatattaattaaaatactatactgtaaattacattttatttacaatcaatactagtaaaaggtaggttcaaccactgatg cctaggcacaccgaaacgactaaccctaattcttatcctttacttcaggcgcgcccggcttaagcgtacgaacttaaaaaaaaaaatca aatTGTTTTatgtcttttgttgatcaccctccagattggttggaagaagttggtgaaggtcttcgcgagtttttgggccttgaagcgg gcccaccgaaaccaaaacccaatcagcagcatcaagatcaagcccgtggtcttgtgctgcctggttataactatctcggacccggaa acggtctcgatcgaggagagcctgtcaacagggcagacgaggtcgcgcgagagcacgacatctcgtacaacgagcagcttgagg cgggagacaacccctacctcaagtacaaccacgcggacgccgagtttcaggagaagctcgccgacgacacatccttcgggggaa acctcggaaaggcagtctttcaggccaagaaaagggttctcgaaccttttggcctggttgaagagggtgctaagacggcccctaccg gaaagcggatagacgaccactttccaaaaagaaagaaggctcggaccgaagaggactccaagccttccacctcgtcagacgccg aagctggacccagcggatcccagcagctgcaaatcccagcccaaccagcctcaagtttgggagctgatacaatgtctgcgggaggt ggcggcccattgggcgacaataaccaaggtgccgatggagtgggcaatgcctcgggagattggcattgcgattccacgtggatgg gggacagagtcgtcaccaagtccacccgaacctgggtgctgcccagctacaacaaccaccagtaccgagagatcaaaagcggct ccgtcgacggaagcaacgccaacgcctactttggatacagcaccccctgggggtactttgactttaaccgcttccacagccactgga gcccccgagactggcaaagactcatcaacaactactggggcttcagaccccggtccctcagagtcaaaatcttcaacattcaagtca aagaggtcacggtgcaggactccaccaccaccatcgccaacaacctcacctccaccgtccaagtgtttacggacgacgactaccag ctgccctacgtcgtcggcaacgggaccgagggatgcctgccggccttccctccgcaggtctttacgctgccgcagtacggttacgc gacgctgaaccgcgacaacacagaaaatcccaccgagaggagcagcttcttctgcctagagtactttcccagcaagatgctgagaa cgggcaacaactttgagtttacctacaactttgaggaggtgcccttccactccagcttcgctcccagtcagaacctcttcaagctggcc aacccgctggtggaccagtacttgtaccgcttcgtgagcacaaataacactggcggagtccagttcaacaagaacctggccgggag atacgccaacacctacaaaaactggttcccggggcccatgggccgaacccagggctggaacctgggctccggggtcaaccgcgc cagtgtcagcgccttcgccacgaccaataggatggagctcgagggcgcgagttaccaggtgcccccgcagccgaacggcatgac caacaacctccagggcagcaacacctatgccclggagaacactatgatcttcaacagccagccggcgaacccgggcaccaccgc cacgtacctcgagggcaacatgctcatcaccagcgagagcgagacgcagccggtgaaccgcgtggcgtacaacgtcggcgggc agatggccaccaacaaccagagctccaccactgcccccgcgaccggcacgtacaacctccaggaaatcgtgcccggcagcgtgt ggatggagagggacgtgtacctccaaggacccatctgggccaagatcccagagacgggggcgcactttcacccctctccggccat gggcggattcggactcaaacacccaccgcccatgatgctcatcaagaacacgcctgtgcccggaaatatcaccagcttctcggacg tgcccgtcagcagcttcatcacccagtacagcaccgggcaggtcaccgtggagatggagtgggagctcaagaaggaaaactccaa gaggtggaacccagagatccagtacacaaacaactacaacgacccccagtttgtggactttgccccggacagcaccggggaatac agaaccaccagacctatcggaacccgataccttacccgacccctttaagctagcagctgatgcatagcatgcggtaccgggagatg ggggaggctaactgaaacacggaaggagacaataccggaaggaacccgcgctatgacggcaataaaaagacagaataaaacgc acgggtgttgggtcgtttgttcGAGTCATTTAAATACCGGTCTGGGCGAACAAACGATGCTCGC CTTCCAGAAAACCGAGGATGCGAACCACTTCATCCGGGGTCAGCACCACCGGCA AGCGCCGCGACGGCCGAGGTCTTCCGATCTCCTGAAGCCAGGGCAGATCCGTGC ACAGCACCTTGCCGTAGAAGAACAGCAAGGCCGCCAATGCCTGACGATGCGTGG AGACCGAAACCTTGCGCTCGTTCGCCAGCCAGGACAGAAATGCCTCGACTTCGC TGCTGCCCAAGGTTGCCGGGTGACGCACACCGTGGAAACGGATGAAGGCACGA ACCCAGTTGACATAAGCCTGTTCGGTTCGTAAACTGTAATGCAAGTAGCGTATGC GCTCACGCAACTGGTCCAGAACCTTGACCGAACGCAGCGGTGGTAACGGCGCAG TGGCGGTTTTCATGGCTTGTTATGACTGTTTTTTTGTACAGTCTATGCCTCGGGCAT CCAAGCAGCAAGCGCGTTACGCCGTGGGTCGATGTTTGATGTTATGGAGCAGCA ACGATGTTACGCAGCAGCAACGATGTTACGCAGCAGGGCAGTCGCCCTAAAACA AAGTTAGGTGGCTCAAGTATGGGCATCATTCGCACATGTAGGCTCGGCCCTGACC AAGTCAAATCCATGCGGGCTGCTCTTGATCTTTTCGGTCGTGAGTTCGGAGACGT AGCCACCTACTCCCAACATCAGCCGGACTCCGATTACCTCGGGAACTTGCTCCGTAGTAAGACATTCATCGCGCTTGCTGCCTTCGACCAAGAAGCGGTTGTTGGCGCTC TCGCGGCTTACGTTCTGCCCAAGTTTGAGCAGCCGCGTAGTGAGATCTATATCTAT GATCTCGCAGTCTCCGGCGAGCACCGGAGGCAGGGCATTGCCACCGCGCTCATC AATCTCCTCAAGCATGAGGCCAACGCGCTTGGTGCTTATGTGATCTACGTGCAAG CAGATTACGGTGACGATCCCGCAGTGGCTCTCTATACAAAGTTGGGCATACGGGA AGAAGTGATGCACTTTGATATCGACCCAAGTACCGCCACCTAACAATTCGTTCAA GCCGAGATCGGCTTCCCGGCCGCGGAGTTGTTCGGTAAATTGTCACAACGCCGC GAATATAGTCTTTACCATGCCCTTGGCCACGCCCCTCTTTAATACGACGGGCAATT TGCACTTCAGAAAATGAAGAGTTTGCTTTAGCCATAACAAAAGTCCAGTATGCTT TTTCACAGCATAACTGGACTGATTTCAGTTTACAACTATTCTGTCTAGTTTAAGAC TTTATTGTCATAGTTTAGATCTATTTTGTTCAGTTTAAGACTTTATTGTCCGCCCAC ACCCGCTTACGCAGGGCATCCATTTATTACTCAAatcggatcccgggcccgtcgactgcagaggcct gcatgcaagcttggcgtaatcatggtcatagctgtttcctgtgtgaaattgttatccgctcacaattccacacaacatacgagccggaag cataaagtgtaaagcctggggtgcctaatgagtgagctaactcacattaattgcgttgcgctcactgcccgctttccagtcgggaaacc tgtcgtgccagctgcattaatgaatcggccaacgcgcggggagaggcggtttgcgtattgggcgctcttccgcttcctcgctcactga ctcgctgcgctcggtcgttcggctgcggcgagcggtatcagctcactcaaaggcggtaatacggttatccacagaatcaggggataa cgcaggaaagaacatgtgagcaaaaggccagcaaaaggccaggaaccgtaaaaaggccgcgttgctggcgtttttccataggctc cgcccccctgacgagcatcacaaaaatcgacgctcaagtcagaggtggcgaaacccgacaggactataaagataccaggcgtttc cccctggaagctccctcgtgcgctctcctgttccgaccctgccgcttaccggatacctgtccgcctttctcccttcgggaagcgtggcg ctttctcatagctcacgctgtaggtatctcagttcggtgtaggtcgttcgctccaagctgggctgtgtgcacgaaccccccgttcagccc gaccgctgcgccttatccggtaactatcgtcttgagtccaacccggtaagacacgacttatcgccactggcagcagccactggtaaca ggattagcagagcgaggtatgtaggcggtgctacagagttcttgaagtggtggcctaactacggctacactagaagaacagtatttg gtatctgcgctctgctgaagccagttaccttcggaaaaagagttggtagctcttgatccggcaaacaaaccaccgctggtagcggtgg tttttttgtttgcaagcagcagattacgcgcagaaaaaaaggatctcaagaagatcctttgatcttttctacggggtctgacgctcagtgg aacgaaaactcacgttaagggattttggtcatgagattatcaaaaaggatcttcacctagatccttttaaattaaaaatgaagttttaaatc aatctaaagtatatatgagtaaacttggtctgacagttaccaatgcttaatcagtgaggcacctatctcagcgatctgtctatttcgttcatc catagttgcctgactccccgtcgtgtagataactacgatacgggagggcttaccatctggccccagtgctgcaatgataccgcgagac ccacgctcaccggctccagatttatcagcaataaaccagccagccggaagggccgagcgcagaagtggtcctgcaactttatccgc clccalccaglclallaatlgllgccgggaagclagaglaaglagllcgccagtlaalaglllgcgcaacgllgllgccallgclacaggc atcgtggtgtcacgctcgtcgtttggtatggcttcattcagctccggttcccaacgatcaaggcgagttacatgatcccccatgttgtgca aaaaagcggttagctccttcggtcctccgatcgttgtcagaagtaagttggccgcagtgttatcactcatggttatggcagcactgcata attctcttactgtcatgccatccgtaagatgcttttctgtgactggtgagtactcaaccaagtcattctgagaatagtgtatgcggcgaccg agttgctcttgcccggcgtcaatacgggataataccgcgccacatagcagaactttaaaagtgctcatcattggaaaacgttcttcggg gcgaaaactctcaaggatcttaccgctgttgagatccagttcgatgtaacccactcgtgcacccaactgatcttcagcatcttttactttca ccagcgtttctgggtgagcaaaaacaggaaggcaaaatgccgcaaaaaagggaataagggcgacacggaaatgttgaatactcat actcttcctttttcaatattattgaagcatttatcagggttattgtctcatgagcggatacatatttgaatgtatttagaaaaataaacaaatag gggttccgcgcacatttccccgaaaagtgccacctgacgtctaagaaaccattattatcatgacattaacctataaaaataggcgtatca cgaggccctttcgtc pFBacX-AAVRep2ACap5_40CE TMV (SEQ ID NO: 44) tcgcgcgtttcggtgatgacggtgaaaacctctgacacatgcagctcccggagacggtcacagcttgtctgtaagcggatgccggga gcagacaagcccgtcagggcgcgtcagcgggtgttggcgggtgtcggggctggcttaactatgcggcatcagagcagattgtact gagagtgcaccatatgcggtgtgaaataccgcacagatgcgtaaggagaaaataccgcatcaggcgccattcgccattcaggctgc gcaactgttgggaagggcgatcggtgcgggcctcttcgctattacgccagctggcgaaagggggatgtgctgcaaggcgattaagt tgggtaacgccagggttttcccagtcacgacgttgtaaaacgacggccagtgaattcgagctcggtacctcgcgaatgcatctagatGATTAAAAACATAACAGGAAGAAAAATGCCCCGCTGTGGGCGGACAAAATAGTTGGGAACTGGGAGGGGTGGAAATGGAGTTTTTAAGGATTATTTAGGGAAGAGTGA CAAAATAGATGGGAACTGGGTGTAGCGTCGTAAGCTAATACGAAAATTAAAAATG ACAAAATAGTTTGGAACTAGATTTCACTTATCTGGTTcggatctgggtccccctaggctcaagcagt gatcagatccagacatgataagatacattgatgagtttggacaaaccacaactagaatgcagtgaaaaaaatgctttatttgtgaaattt gtgatgctattgctttatttgtaaccattataagctgcaataaacaagttaacaacaacaattgcattcattttatgtttcaggttcaggggga ggtgtgggaggttttttaaagcaagtaaaacctctacaaatgtggtatggctgattatgatcctctagtacttctcgacaagcttgtcgag actgcaggctctagagtcgacctgcaggcatgcaagcttgattcctcgagtttattgttcaaagatgcagtcatccaaatccacattgac cagatcgcaggcagtgcaagcgtctggcacctttcccatgatatgatgaatgtagcacagtttctgatacgcctttttgacgacagaaa cgggttgagattctgacacgggaaagcactctaaacagtctttctgtccgtgagtgaagcagatatttgaattctgattcattctctcgcat tgtctgcagggaaacagcatcagattcatgcccacgtgacgagaacatttgttttggtacctgtctgcgtagttgatcgaagcttccgcg tctgacgtcgatggctgcgcaactgactcgcgcacccgtttgggctcacttatatctgcgtcactgggggcgggtcttttcttggctcca ccctttttgacgtagaattcatgctccacctcaaccacgtgatcctttgcccaccggaaaaagtctttgacttcctgcttggtgaccttccc aaagtcatgatccagacggcgggtgagttcaaatttgaacatccggtcttgcaacggctgctggtgttcgaaggtcgttgagttcccgt caatcacggcgcacatgttggtgttggaggtgacgatcacgggagtcgggtctatctgggccgaggacttgcatttctggtccacgc gcaccttgcttcctccgagaatggctttggccgactccacgaccttggcggtcatcttcccctcctcccaccagatcaccatcttgtcga cacagtcgttgaagggaaagttctcattggtccagtttacgcacccgtagaagggcacagtgtgggctatggcctccgcgatgttggt cttcccggtagttgcaggcccaaacagccagatggtgttcctcttgccgaactttttcgtggcccatcccagaaagacggaagccgca tattggggatcgtacccgtttagttccaaaattttataaatccgattgctggaaatgtcctccacgggctgctggcccaccaggtagtcg ggggcggttttagtcaggctcataatctttcccgcattgtccaaggcagccttgatttgggaccgcgagttggaggccgcattgaagg agatgtatgaAgcctggtcctcctggatccactgcttctccgaggtaatccccttgtccacgagccacccgaccagctccatgtacct ggctgaagtttttgatctgatcaccggcgcgtcagaattgggattctgattctctttgttctgctcctgcgtctgcgacacgtgcgtcagat gctgcgccaccaaccgtttacgctccgtgagattcaaacaggcgcttaaatactgttctaaattagtccacgcccactggagctcagg ctgggttttggggagcaagtaattggggatgtagcactcgtccaccaccttgttcccgcctccggcgccgtttctggtctttgtgaccgc gaaccagtttggcaaagtcggctcgatcccgcggtaaattctctgaatcagtttttcgcgaatctgactcaggaaacgtcccaaaacta aggatttcaccccggtggtttccacgagcacgtgtaagtggaagtagctctctcccttctcaaattgcacaaagaaaagggcctccgg ggccttactcacacggcgccactccgtcagaaagtcgcgctgcagcttctcggccacggtcaggggtgcctgctcaatcagattcag atccaagtcagaatctggcggcaactcccactccttctcggccacccagttcacaaagctgtcagaaatgccgggcagatgctcgtc aaggtcgctggggaccttaatcacaatctcgtaaaaccccgccagggcggcagatccgcgcccgatggtGCGGCCGCacg gtatgaataatccggaatatttataggUtttttattacaaaactgttacgaaaacagtaaaatacttatttatttgcgagatggttatcatttta attatctccatgatctattaatattcACGCGTcggagtatacggacctttaattcaacccaacacaatatattatagttaaataagaatt attatcaaatcatttgtatattaattaaaatactatactgtaaattacattttatttacaatcaatactagtaaaaggtaggttcaaccactgatg cctaggcacaccgaaacgactaaccctaattcttatcctttacttcaggcgcgcccggcttaagcgtacgGTATTTTTACAA CAATTACCAACAACAACAAACCAACAAACAACATTACAATTACTATTTACAATTA CtTGTTTTatgtcttttgttgatcaccctccagattggttggaagaagttggtgaaggtcttcgcgagtttttgggccttgaagcggg cccaccgaaaccaaaacccaatcagcagcatcaagatcaagcccgtggtcttgtgctgcctggttataactatctcggacccggaaa cggtctcgatcgaggagagcctgtcaacagggcagacgaggtcgcgcgagagcacgacatctcgtacaacgagcagcttgaggc gggagacaacccctacctcaagtacaaccacgcggacgccgagtttcaggagaagctcgccgacgacacatccttcgggggaaa cctcggaaaggcagtctttcaggccaagaaaagggttctcgaaccttttggcctggttgaagagggtgctaagacggcccctaccgg aaagcggatagacgaccactttccaaaaagaaagaaggctcggaccgaagaggactccaagccttccacctcgtcagacgccgaa gctggacccagcggatcccagcagctgcaaatcccagcccaaccagcctcaagtttgggagctgatacaatgtctgcgggaggtg gcggcccattgggcgacaataaccaaggtgccgatggagtgggcaatgcctcgggagattggcattgcgattccacgtggatggg ggacagagtcgtcaccaagtccacccgaacctgggtgctgcccagctacaacaaccaccagtaccgagagatcaaaagcggctcc gtcgacggaagcaacgccaacgcctactttggatacagcaccccctgggggtactttgactttaaccgcttccacagccactggagc ccccgagactggcaaagactcatcaacaactactggggcttcagaccccggtccctcagagtcaaaatcttcaacattcaagtcaaa gaggtcacggtgcaggactccaccaccaccatcgccaacaacctcacctccaccgtccaagtgtttacggacgacgactaccagct gccctacgtcgtcggcaacgggaccgagggatgcctgccggccttccctccgcaggtctttacgctgccgcagtacggttacgcga cgctgaaccgcgacaacacagaaaatcccaccgagaggagcagcttcttctgcctagagtactttcccagcaagatgctgagaacg ggcaacaactttgagtttacctacaactttgaggaggtgcccttccactccagcttcgctcccagtcagaacctcttcaagctggccaa cccgctggtggaccagtacttgtaccgcttcgtgagcacaaataacactggcggagtccagttcaacaagaacctggccgggagatacgccaacacctacaaaaactggttcccggggcccatgggccgaacccagggctggaacctgggctccggggtcaaccgcgcca gtgtcagcgccttcgccacgaccaataggatggagctcgagggcgcgagttaccaggtgcccccgcagccgaacggcatgacca acaacctccagggcagcaacacctatgccctggagaacactatgatcttcaacagccagccggcgaacccgggcaccaccgcca cgtacctcgagggcaacatgctcatcaccagcgagagcgagacgcagccggtgaaccgcgtggcgtacaacgtcggcgggcag atggccaccaacaaccagagctccaccactgcccccgcgaccggcacgtacaacctccaggaaatcgtgcccggcagcgtgtgg atggagagggacgtgtacctccaaggacccatctgggccaagatcccagagacgggggcgcactttcacccctctccggccatgg gcggattcggactcaaacacccaccgcccatgatgctcatcaagaacacgcctgtgcccggaaatatcaccagcttctcggacgtgc ccgtcagcagcttcatcacccagtacagcaccgggcaggtcaccgtggagatggagtgggagctcaagaaggaaaactccaaga ggtggaacccagagatccagtacacaaacaactacaacgacccccagtttgtggactttgccccggacagcaccggggaatacag aaccaccagacctatcggaacccgataccttacccgacccctttaagctagcagctgatgcatagcatgcggtaccgggagatggg ggaggctaactgaaacacggaaggagacaataccggaaggaacccgcgctatgacggcaataaaaagacagaataaaacgcac gggtgttgggtcgtttgttcGAGTCATTTAAATACCGGTCTGGGCGAACAAACGATGCTCGCC TTCCAGAAAACCGAGGATGCGAACCACTTCATCCGGGGTCAGCACCACCGGCAA GCGCCGCGACGGCCGAGGTCTTCCGATCTCCTGAAGCCAGGGCAGATCCGTGCA CAGCACCTTGCCGTAGAAGAACAGCAAGGCCGCCAATGCCTGACGATGCGTGGA GACCGAAACCTTGCGCTCGTTCGCCAGCCAGGACAGAAATGCCTCGACTTCGCT GCTGCCCAAGGTTGCCGGGTGACGCACACCGTGGAAACGGATGAAGGCACGAA CCCAGTTGACATAAGCCTGTTCGGTTCGTAAACTGTAATGCAAGTAGCGTATGCG CTCACGCAACTGGTCCAGAACCTTGACCGAACGCAGCGGTGGTAACGGCGCAGT GGCGGTTTTCATGGCTTGTTATGACTGTTTTTTTGTACAGTCTATGCCTCGGGCAT CCAAGCAGCAAGCGCGTTACGCCGTGGGTCGATGTTTGATGTTATGGAGCAGCA ACGATGTTACGCAGCAGCAACGATGTTACGCAGCAGGGCAGTCGCCCTAAAACA AAGTTAGGTGGCTCAAGTATGGGCATCATTCGCACATGTAGGCTCGGCCCTGACC AAGTCAAATCCATGCGGGCTGCTCTTGATCTTTTCGGTCGTGAGTTCGGAGACGT AGCCACCTACTCCCAACATCAGCCGGACTCCGATTACCTCGGGAACTTGCTCCGT AGTAAGACATTCATCGCGCTTGCTGCCTTCGACCAAGAAGCGGTTGTTGGCGCTC TCGCGGCTTACGTTCTGCCCAAGTTTGAGCAGCCGCGTAGTGAGATCTATATCTAT GATCTCGCAGTCTCCGGCGAGCACCGGAGGCAGGGCATTGCCACCGCGCTCATC AATCTCCTCAAGCATGAGGCCAACGCGCTTGGTGCTTATGTGATCTACGTGCAAG CAGATTACGGTGACGATCCCGCAGTGGCTCTCTATACAAAGTTGGGCATACGGGA AGAAGTGATGCACTTTGATATCGACCCAAGTACCGCCACCTAACAATTCGTTCAA GCCGAGATCGGCTTCCCGGCCGCGGAGTTGTTCGGTAAATTGTCACAACGCCGC GAATATAGTCTTTACCATGCCCTTGGCCACGCCCCTCTTTAATACGACGGGCAATT TGCACTTCAGAAAATGAAGAGTTTGCTTTAGCCATAACAAAAGTCCAGTATGCTT TTTCACAGCATAACTGGACTGATTTCAGTTTACAACTATTCTGTCTAGTTTAAGAC TTTATTGTCATAGTTTAGATCTATTTTGTTCAGTTTAAGACTTTATTGTCCGCCCAC ACCCGCTTACGCAGGGCATCCATTTATTACTCAAatcggatcccgggcccgtcgactgcagaggcct gcatgcaagcttggcgtaatcatggtcatagctgtttcctgtgtgaaattgttatccgctcacaattccacacaacatacgagccggaag cataaagtgtaaagcctggggtgcctaatgagtgagctaactcacattaattgcgttgcgctcactgcccgctttccagtcgggaaacc tgtcgtgccagctgcattaatgaatcggccaacgcgcggggagaggcggtttgcgtattgggcgctcttccgcttcctcgctcactga ctcgctgcgctcggtcgttcggctgcggcgagcggtatcagctcactcaaaggcggtaatacggttatccacagaatcaggggataa cgcaggaaagaacatgtgagcaaaaggccagcaaaaggccaggaaccgtaaaaaggccgcgttgctggcgtttttccataggctc cgcccccctgacgagcatcacaaaaatcgacgctcaagtcagaggtggcgaaacccgacaggactataaagataccaggcgtttc cccctggaagctccctcgtgcgctctcctgttccgaccctgccgcttaccggatacctgtccgcctttctcccttcgggaagcgtggcg ctttctcatagctcacgctgtaggtatctcagttcggtgtaggtcgttcgctccaagctgggctgtgtgcacgaaccccccgttcagccc gaccgctgcgccttatccggtaactatcgtcttgagtccaacccggtaagacacgacttatcgccactggcagcagccactggtaaca ggattagcagagcgaggtatgtaggcggtgctacagagttcttgaagtggtggcctaactacggctacactagaagaacagtatttg gtatctgcgctctgctgaagccagttaccttcggaaaaagagttggtagctcttgatccggcaaacaaaccaccgctggtagcggtgg tttttttgtttgcaagcagcagattacgcgcagaaaaaaaggatctcaagaagatcctttgatcttttctacggggtctgacgctcagtggaacgaaaactcacgttaagggattttggtcatgagattatcaaaaaggatcttcacctagatccttttaaattaaaaatgaagttttaaatc aatctaaagtatatatgagtaaacttggtctgacagttaccaatgcttaatcagtgaggcacctatctcagcgatctgtctatttcgttcatc catagttgcctgactccccgtcgtgtagataactacgatacgggagggcttaccatctggccccagtgctgcaatgataccgcgagac ccacgctcaccggctccagatttatcagcaataaaccagccagccggaagggccgagcgcagaagtggtcctgcaactttatccgc ctccatccagtctattaattgttgccgggaagctagagtaagtagttcgccagttaatagtttgcgcaacgttgttgccattgctacaggc atcgtggtgtcacgctcgtcgtttggtatggcttcattcagctccggttcccaacgatcaaggcgagttacatgatcccccatgttgtgca aaaaagcggttagctccttcggtcctccgatcgttgtcagaagtaagttggccgcagtgttatcactcatggttatggcagcactgcata attctcttactgtcatgccatccgtaagatgcttttctgtgactggtgagtactcaaccaagtcattctgagaatagtgtatgcggcgaccg agttgctcttgcccggcgtcaatacgggataataccgcgccacatagcagaactttaaaagtgctcatcattggaaaacgttcttcggg gcgaaaactctcaaggatcttaccgctgttgagatccagttcgatgtaacccactcgtgcacccaactgatcttcagcatcttttactttca ccagcgtttctgggtgagcaaaaacaggaaggcaaaatgccgcaaaaaagggaataagggcgacacggaaatgttgaatactcat actcttcctttttcaatattattgaagcatttatcagggttattgtctcatgagcggatacatatttgaatgtatttagaaaaataaacaaatag gggttccgcgcacatttccccgaaaagtgccacctgacgtctaagaaaccattattatcatgacattaacctataaaaataggcgtatca cgaggccctttcgtc pFBacX-AAVRep2ACap5_44AE L21 (SEQ ID NO: 45) tcgcgcgtttcggtgatgacggtgaaaacctctgacacatgcagctcccggagacggtcacagcttgtctgtaagcggatgccggga gcagacaagcccgtcagggcgcgtcagcgggtgttggcgggtgtcggggctggcttaactatgcggcatcagagcagattgtact gagagtgcaccatatgcggtgtgaaataccgcacagatgcgtaaggagaaaataccgcatcaggcgccattcgccattcaggctgc gcaactgttgggaagggcgatcggtgcgggcctcttcgctattacgccagctggcgaaagggggatgtgctgcaaggcgattaagt tgggtaacgccagggttttcccagtcacgacgttgtaaaacgacggccagtgaattcgagctcggtacctcgcgaatgcatctagat GATTAAAAACATAACAGGAAGAAAAATGCCCCGCTGTGGGCGGACAAAATAGTT GGGAACTGGGAGGGGTGGAAATGGAGTTTTTAAGGATTATTTAGGGAAGAGTGA CAAAATAGATGGGAACTGGGTGTAGCGTCGTAAGCTAATACGAAAATTAAAAATG ACAAAATAGTTTGGAACTAGATTTCACTTATCTGGTTcggatctgggtccccctaggctcaagcagt gatcagatccagacatgataagatacattgatgagtttggacaaaccacaactagaatgcagtgaaaaaaatgctttatttgtgaaattt gtgatgctattgctttatttgtaaccattataagctgcaataaacaagttaacaacaacaattgcattcattttatgtttcaggttcaggggga ggtgtgggaggttttttaaagcaagtaaaacctctacaaatgtggtatggctgattatgatcctctagtacttctcgacaagcttgtcgag actgcaggctctagagtcgacctgcaggcatgcaagcttgattcctcgagtttattgttcaaagatgcagtcatccaaatccacattgac cagatcgcaggcagtgcaagcgtctggcacctttcccatgatatgatgaatgtagcacagtttctgatacgcctttttgacgacagaaa cgggttgagattctgacacgggaaagcactctaaacagtctttctgtccgtgagtgaagcagatatttgaattctgattcattctctcgcat tgtctgcagggaaacagcatcagattcatgcccacgtgacgagaacatttgttttggtacctgtctgcgtagttgatcgaagcttccgcg tctgacgtcgatggctgcgcaactgactcgcgcacccgtttgggctcacttatatctgcgtcactgggggcgggtcttttcttggctcca ccctttttgacgtagaattcatgctccacctcaaccacgtgatcctttgcccaccggaaaaagtctttgacttcctgcttggtgaccttccc aaagtcatgatccagacggcgggtgagttcaaatttgaacatccggtcttgcaacggctgctggtgttcgaaggtcgttgagttcccgt caatcacggcgcacatgttggtgttggaggtgacgatcacgggagtcgggtctatctgggccgaggacttgcatttctggtccacgc gcaccttgcttcctccgagaatggctttggccgactccacgaccttggcggtcatcttcccctcctcccaccagatcaccatcttgtcga cacagtcgttgaagggaaagttctcattggtccagtttacgcacccgtagaagggcacagtgtgggctatggcctccgcgatgttggt cttcccggtagttgcaggcccaaacagccagatggtgttcctcttgccgaactttttcgtggcccatcccagaaagacggaagccgca tattggggatcgtacccgtttagttccaaaattttataaatccgattgctggaaatgtcctccacgggctgctggcccaccaggtagtcg ggggcggttttagtcaggctcataatctttcccgcattgtccaaggcagccttgatttgggaccgcgagttggaggccgcattgaagg agatgtatgaAgcctggtcctcctggatccactgcttctccgaggtaatccccttgtccacgagccacccgaccagctccatgtacct ggctgaagtttttgatctgatcaccggcgcgtcagaattgggattctgattctctttgttctgctcctgcgtctgcgacacgtgcgtcagat gctgcgccaccaaccgtttacgctccgtgagattcaaacaggcgcttaaatactgttctaaattagtccacgcccactggagctcagg ctgggttttggggagcaagtaattggggatgtagcactcgtccaccaccttgttcccgcctccggcgccgtttctggtctttgtgaccgc gaaccagtttggcaaagtcggctcgatcccgcggtaaattctctgaatcagtttttcgcgaatctgactcaggaaacgtcccaaaactaaggatttcaccccggtggtttccacgagcacgtgtaagtggaagtagctctctcccttctcaaattgcacaaagaaaagggcctccgg ggccttactcacacggcgccactccgtcagaaagtcgcgctgcagcttctcggccacggtcaggggtgcctgctcaatcagattcag atccaagtcagaatctggcggcaactcccactccttctcggccacccagttcacaaagctgtcagaaatgccgggcagatgctcgtc aaggtcgctggggaccttaatcacaatctcgtaaaaccccgccagggcggcagatccgcgcccgatggtGCGGCCGCacg gtatgaataatccggaatatttataggtttttttattacaaaactgttacgaaaacagtaaaatacttatttatttgcgagatggttatcatttta attatctccatgatctattaatattcACGCGTcggagtatacggacctttaattcaacccaacacaatatattatagttaaataagaatt attatcaaatcatttgtatattaattaaaatactatactgtaaattacattttatttacaatcaatactagtaaaaggtaggttcaaccactgatg cctaggcacaccgaaacgactaaccctaattcttatcctttacttcaggcgcgcccggcttaagcgtacgAACTCCTAAAA AACCGCCACCTtTTTTatgtcttttgttgatcaccctccagattggttggaagaagttggtgaaggtcttcgcgagtttttgg gccttgaagcgggcccaccgaaaccaaaacccaatcagcagcatcaagatcaagcccgtggtcttgtgctgcctggttataactatct cggacccggaaacggtctcgatcgaggagagcctgtcaacagggcagacgaggtcgcgcgagagcacgacatctcgtacaacg agcagcttgaggcgggagacaacccctacctcaagtacaaccacgcggacgccgagtttcaggagaagctcgccgacgacacat ccttcgggggaaacctcggaaaggcagtctttcaggccaagaaaagggttctcgaaccttttggcctggttgaagagggtgctaaga cggcccctaccggaaagcggatagacgaccactttccaaaaagaaagaaggctcggaccgaagaggactccaagccttccacctc gtcagacgccgaagctggacccagcggatcccagcagctgcaaatcccagcccaaccagcctcaagtttgggagctgatacaatg tctgcgggaggtggcggcccattgggcgacaataaccaaggtgccgatggagtgggcaatgcctcgggagattggcattgcgatt ccacgtggatgggggacagagtcgtcaccaagtccacccgaacctgggtgctgcccagctacaacaaccaccagtaccgagagat caaaagcggctccgtcgacggaagcaacgccaacgcctactttggatacagcaccccctgggggtactttgactttaaccgcttcca cagccactggagcccccgagactggcaaagactcatcaacaactactggggcttcagaccccggtccctcagagtcaaaatcttca acattcaagtcaaagaggtcacggtgcaggactccaccaccaccatcgccaacaacctcacctccaccgtccaagtgtttacggacg acgactaccagctgccctacgtcgtcggcaacgggaccgagggatgcctgccggccttccctccgcaggtctttacgctgccgcag tacggttacgcgacgctgaaccgcgacaacacagaaaatcccaccgagaggagcagcttcttctgcctagagtactttcccagcaa gatgctgagaacgggcaacaactttgagtttacctacaactttgaggaggtgcccttccactccagcttcgctcccagtcagaacctctt caagctggccaacccgctggtggaccagtacttgtaccgcttcgtgagcacaaataacactggcggagtccagttcaacaagaacct ggccgggagatacgccaacacctacaaaaactggttcccggggcccatgggccgaacccagggctggaacctgggctccgggg tcaaccgcgccagtgtcagcgccttcgccacgaccaataggatggagctcgagggcgcgagttaccaggtgcccccgcagccga acggcatgaccaacaacctccagggcagcaacacctatgccctggagaacactatgalcttcaacagccagccggcgaacccggg caccaccgccacgtacctcgagggcaacatgctcatcaccagcgagagcgagacgcagccggtgaaccgcgtggcgtacaacgt cggcgggcagatggccaccaacaaccagagctcc accactgcccccgcgaccggcacgtacaacctccaggaaatcgtgcccg gcagcgtgtggatggagagggacgtgtacctccaaggacccatctgggccaagatcccagagacgggggcgcactttcacccctc tccggccatgggcggattcggactcaaacacccaccgcccatgatgctcatcaagaacacgcctgtgcccggaaatatcaccagctt ctcggacgtgcccgtcagcagcttcatcacccagtacagcaccgggcaggtcaccgtggagatggagtgggagctcaagaagga aaactccaagaggtggaacccagagatccagtacacaaacaactacaacgacccccagtttgtggactttgccccggacagcaccg gggaatacagaaccaccagacctatcggaacccgataccttacccgacccctttaagctagcagctgatgcatagcatgcggtaccg ggagatgggggaggctaactgaaacacggaaggagacaataccggaaggaacccgcgctatgacggcaataaaaagacagaat aaaacgcacgggtgttgggtcgtttgttcGAGTCATTTAAATACCGGTCTGGGCGAACAAACGATG CTCGCCTTCCAGAAAACCGAGGATGCGAACCACTTCATCCGGGGTCAGCACCAC CGGCAAGCGCCGCGACGGCCGAGGTCTTCCGATCTCCTGAAGCCAGGGCAGATC CGTGCACAGCACCTTGCCGTAGAAGAACAGCAAGGCCGCCAATGCCTGACGATG CGTGGAGACCGAAACCTTGCGCTCGTTCGCCAGCCAGGACAGAAATGCCTCGAC TTCGCTGCTGCCCAAGGTTGCCGGGTGACGCACACCGTGGAAACGGATGAAGGC ACGAACCCAGTTGACATAAGCCTGTTCGGTTCGTAAACTGTAATGCAAGTAGCGT ATGCGCTCACGCAACTGGTCCAGAACCTTGACCGAACGCAGCGGTGGTAACGGC GCAGTGGCGGTTTTCATGGCTTGTTATGACTGTTTTTTTGTACAGTCTATGCCTCG GGCATCCAAGCAGCAAGCGCGTTACGCCGTGGGTCGATGTTTGATGTTATGGAGC AGCAACGATGTTACGCAGCAGCAACGATGTTACGCAGCAGGGCAGTCGCCCTAA AACAAAGTTAGGTGGCTCAAGTATGGGCATCATTCGCACATGTAGGCTCGGCCCT GACCAAGTCAAATCCATGCGGGCTGCTCTTGATCTTTTCGGTCGTGAGTTCGGAG ACGTAGCCACCTACTCCCAACATCAGCCGGACTCCGATTACCTCGGGAACTTGCTCCGTAGTAAGACATTCATCGCGCTTGCTGCCTTCGACCAAGAAGCGGTTGTTGGC GCTCTCGCGGCTTACGTTCTGCCCAAGTTTGAGCAGCCGCGTAGTGAGATCTATAT CTATGATCTCGCAGTCTCCGGCGAGCACCGGAGGCAGGGCATTGCCACCGCGCT CATCAATCTCCTCAAGCATGAGGCCAACGCGCTTGGTGCTTATGTGATCTACGTGC AAGCAGATTACGGTGACGATCCCGCAGTGGCTCTCTATACAAAGTTGGGCATACG GGAAGAAGTGATGCACTTTGATATCGACCCAAGTACCGCCACCTAACAATTCGTT CAAGCCGAGATCGGCTTCCCGGCCGCGGAGTTGTTCGGTAAATTGTCACAACGC CGCGAATATAGTCTTTACCATGCCCTTGGCCACGCCCCTCTTTAATACGACGGGCA ACTTTTTTGTTCCAACCTATCGACGATAAAAACATTGGGAAACGTAGGATTTTTTGCCATGTTTTATGACCCAAATCATAACTATACATGATGCTTCACGATGTTTAATAG GACTTTATTGTCATAGTTTAGATCTATTTTGTTCAGTTTAAGACTTTATTGTCCGCC CACACCCGCTTACGCAGGGCATCCATTTATTACTCAAatcggatcccgggcccgtcgactgcagag gcctgcatgcaagcttggcgtaatcatggtcatagctgtttcctgtgtgaaattgttatccgctcacaattccacacaacatacgagccg gaagcataaagtgtaaagcctggggtgcctaatgagtgagctaactcacattaattgcgttgcgctcactgcccgctttccagtcggga aacctgtcgtgccagctgcattaatgaatcggccaacgcgcggggagaggcggtttgcgtattgggcgctcttccgcttcctcgctca ctgactcgctgcgctcggtcgttcggctgcggcgagcggtatcagctcactcaaaggcggtaatacggttatccacagaatcagggg ataacgcaggaaagaacatgtgagcaaaaggccagcaaaaggccaggaaccgtaaaaaggccgcgttgctggcgtttttccatag gctccgcccccctgacgagcatcacaaaaatcgacgctcaagtcagaggtggcgaaacccgacaggactataaagataccaggc gtttccccctggaagctccctcgtgcgctctcctgttccgaccctgccgcttaccggatacctgtccgcctttctcccttcgggaagcgt ggcgctttctcatagctcacgctgtaggtatctcagttcggtgtaggtcgttcgctccaagctgggctgtgtgcacgaaccccccgttca gcccgaccgctgcgccttatccggtaactatcgtcttgagtccaacccggtaagacacgacttatcgccactggcagcagccactgg taacaggattagcagagcgaggtatgtaggcggtgctacagagttcttgaagtggtggcctaactacggctacactagaagaacagt atttggtatctgcgctctgctgaagccagttaccttcggaaaaagagttggtagctcttgatccggcaaacaaaccaccgctggtagcg gtggtttttttgtttgcaagcagcagattacgcgcagaaaaaaaggatctcaagaagatcctttgatcttttctacggggtctgacgctca gtggaacgaaaactcacgttaagggattttggtcatgagattatcaaaaaggatcttcacctagatccttttaaattaaaaatgaagtttta aatcaatctaaagtatatatgagtaaacttggtctgacagttaccaatgcttaatcagtgaggcacctatctcagcgatctgtctatttcgtt catccatagttgcctgactccccgtcgtgtagataactacgatacgggagggcttaccatctggccccagtgctgcaatgataccgcg agacccacgctcaccggctccagatttatcagcaataaaccagccagccggaagggccgagcgcagaagtggtcctgcaactttat ccgcctccatccagtctattaattgttgccgggaagctagagtaagtagttcgccagttaatagtttgcgcaacgttgttgccattgctac aggcatcgtggtgtcacgctcgtcgtttggtatggcttcattcagctccggttcccaacgatcaaggcgagttacatgatcccccatgtt gtgcaaaaaagcggttagctccttcggtcctccgatcgttgtcagaagtaagttggccgcagtgttatcactcatggttatggcagcact gcataattctcttactgtcatgccatccgtaagatgcttttctgtgactggtgagtactcaaccaagtcattctgagaatagtgtatgcggc gaccgagttgctcttgcccggcgtcaatacgggataataccgcgccacatagcagaactttaaaagtgctcatcattggaaaacgttct tcggggcgaaaactctcaaggatcttaccgctgttgagatccagttcgatgtaacccactcgtgcacccaactgatcttcagcatctttt actttcaccagcgtttctgggtgagcaaaaacaggaaggcaaaatgccgcaaaaaagggaataagggcgacacggaaatgttgaat actcatactcttcctttttcaatattattgaagcatttatcagggttattgtctcatgagcggatacatatttgaatgtatttagaaaaataaaca aataggggttccgcgcacatttccccgaaaagtgccacctgacgtctaagaaaccattattatcatgacattaacctataaaaataggc gtatcacgaggccctttcgtc pB-40A-Rep2Cap5 (SEQ ID NO: 46) tcgcgcgtttcggtgatgacggtgaaaacctctgacacatgcagctcccggagacggtcacagcttgtctgtaagcggatgccggga gcagacaagcccgtcagggcgcgtcagcgggtgttggcgggtgtcggggctggcttaactatgcggcatcagagcagattgtact gagagtgcaccatatgcggtgtgaaataccgcacagatgcgtaaggagaaaataccgcatcaggcgccattcgccattcaggctgc gcaactgttgggaagggcgatcggtgcgggcctcttcgctattacgccagctggcgaaagggggatgtgctgcaaggcgattaagt tgggtaacgccagggttttcccagtcacgacgttgtaaaacgacggccagtgaattcgagctcggtacctcgcgaatgcatctagatGATTAAAAACATAACAGGAAGAAAAATGCCCCGCTGTGGGCGGACAAAATAGTTGGGAACTGGGAGGGGTGGAAATGGAGTTTTTAAGGATTATTTAGGGAAGAGTGA CAAAATAGATGGGAACTGGGTGTAGCGTCGTAAGCTAATACGAAAATTAAAAATG ACAAAATAGTTTGGAACTAGATTTCACTTATCTGGTTcggatctgggtccccctaggctcaagcagt gatcagatccagacatgataagatacattgatgagtttggacaaaccacaactagaatgcagtgaaaaaaatgctttatttgtgaaattt gtgatgctattgctttatttgtaaccattataagctgcaataaacaagttaacaacaacaattgcattcattttatgtttcaggttcaggggga ggtgtgggaggttttttaaagcaagtaaaacctctacaaatgtggtatggctgattatgatcctctagtacttctcgacaagcttgtcgag actgcaggctctagagtcgacctgcaggcatgcaagcttgattcctcgagtttattgttcaaagatgcagtcatccaaatccacattgac cagatcgcaggcagtgcaagcgtctggcacctttcccatgatatgatgaatgtagcacagtttctgatacgcctttttgacgacagaaa cgggttgagattctgacacgggaaagcactctaaacagtctttctgtccgtgagtgaagcagatatttgaattctgattcattctctcgcat tgtctgcagggaaacagcatcagattcatgcccacgtgacgagaacatttgttttggtacctgtctgcgtagttgatcgaagcttccgcg tctgacgtcgatggctgcgcaactgactcgcgcacccgtttgggctcacttatatctgcgtcactgggggcgggtcttttcttggctcca ccctttttgacgtagaattcatgctccacctcaaccacgtgatcctttgcccaccggaaaaagtctttgacttcctgcttggtgaccttccc aaagtcatgatccagacggcgggtgagttcaaatttgaacatccggtcttgcaacggctgctggtgttcgaaggtcgttgagttcccgt caatcacggcgcacatgttggtgttggaggtgacgatcacgggagtcgggtctatctgggccgaggacttgcatttctggtccacgc gcaccttgcttcctccgagaatggctttggccgactccacgaccttggcggtcatcttcccctcctcccaccagatcaccatcttgtcga cacagtcgttgaagggaaagttctcattggtccagtttacgcacccgtagaagggcacagtgtgggctatggcctccgcgatgttggt cttcccggtagttgcaggcccaaacagccagatggtgttcctcttgccgaactttttcgtggcccatcccagaaagacggaagccgca tattggggatcgtacccgtttagttccaaaattttataaatccgattgctggaaatgtcctccacgggctgctggcccaccaggtagtcg ggggcggttttagtcaggctcataatctttcccgcattgtccaaggcagccttgatttgggaccgcgagttggaggccgcattgaagg agatgtatgaAgcctggtcctcctggatccactgcttctccgaggtaatccccttgtccacgagccacccgaccagctccatgtacct ggctgaagtttttgatctgatcaccggcgcgtcagaattgggattctgattctctttgttctgctcctgcgtctgcgacacgtgcgtcagat gctgcgccaccaaccgtttacgctccgtgagattcaaacaggcgcttaaatactgttctaaattagtccacgcccactggagctcagg ctgggttttggggagcaagtaattggggatgtagcactcgtccaccaccttgttcccgcctccggcgccgtttctggtctttgtgaccgc gaaccagtttggcaaagtcggctcgatcccgcggtaaattctctgaatcagtttttcgcgaatctgactcaggaaacgtcccaaaacta aggatttcaccccggtggtttccacgagcacgtgtaagtggaagtagctctctcccttctcaaattgcacaaagaaaagggcctccgg ggccttactcacacggcgccactccgtcagaaagtcgcgctgcagcttctcggccacggtcaggggtgcctgctcaatcagattcag atccaagtcagaatctggcggcaactcccactccttctcggccacccagttcacaaagctgtcagaaatgccgggcagatgctcgtc aaggtcgctggggaccttaatcacaatctcgtaaaaccccgccaTAAAATATTTGTTATATAATTTGTAATTgg cggcagatccgcgcccgatggtGCGGCCGCacggtatgaataatccggaatatttataggtttttttattacaaaactgttacgaa aacagtaaaatacttatttatttgcgagatggttatcattttaattatctccatgatctattaatattcACGCGTcggagtatacggacct ttaattcaacccaacacaatatattatagttaaataagaattattatcaaatcatttgtatattaattaaaatactatactgtaaattacattttatt tacaatcaatactagtaaaaggtaggttcaaccactgatgcctaggcacaccgaaacgactaaccctaattcttatcctttacttcaggc gcgcccggcttaagcgtacgaacttaaaaaaaaaaatcaaaTATTTTatgtcttttgttgatcaccctccagattggttggaagaag ttggtgaaggtcttcgcgagtttttgggccttgaagcgggcccaccgaaaccaaaacccaatcagcagcatcaagatcaagcccgtg gtcttgtgctgcctggttataactatctcggacccggaaacggtctcgatcgaggagagcctgtcaacagggcagacgaggtcgcgc gagagcacgacatctcgtacaacgagcagcttgaggcgggagacaacccctacctcaagtacaaccacgcggacgccgagtttca ggagaagctcgccgacgacacatccttcgggggaaacctcggaaaggcagtctttcaggccaagaaaagggttctcgaaccttttg gcctggttgaagagggtgctaagacggcccctaccggaaagcggatagacgaccactttccaaaaagaaagaaggctcggaccg aagaggactccaagccttccacctcgtcagacgccgaagctggacccagcggatcccagcagctgcaaatcccagcccaaccag cctcaagtttgggagctgatacaatgtctgcgggaggtggcggcccattgggcgacaataaccaaggtgccgatggagtgggcaat gcctcgggagattggcattgcgattccacgtggatgggggacagagtcgtcaccaagtccacccgaacctgggtgctgcccagcta caacaaccaccagtaccgagagatcaaaagcggctccgtcgacggaagcaacgccaacgcctactttggatacagcaccccctgg gggtactttgactttaaccgcttccacagccactggagcccccgagactggcaaagactcatcaacaactactggggcttcagaccc cggtccctcagagtcaaaatcttcaacattcaagtcaaagaggtcacggtgcaggactccaccaccaccatcgccaacaacctcacc tccaccgtccaagtgtttacggacgacgactaccagctgccctacgtcgtcggcaacgggaccgagggatgcctgccggccttccc tccgcaggtctttacgctgccgcagtacggttacgcgacgctgaaccgcgacaacacagaaaatcccaccgagaggagcagcttct tctgcctagagtactttcccagcaagatgctgagaacgggcaacaactttgagtttacctacaactttgaggaggtgcccttccactcca gcttcgctcccagtcagaacctcttcaagctggccaacccgctggtggaccagtacttgtaccgcttcgtgagcacaaataacactgg cggagtccagttcaacaagaacctggccgggagatacgccaacacctacaaaaactggttcccggggcccatgggccgaacccagggctggaacctgggctccggggtcaaccgcgccagtgtcagcgccttcgccacgaccaataggatggagctcgagggcgcga gttaccaggtgcccccgcagccgaacggcatgaccaacaacctccagggcagcaacacctatgccctggagaacactatgatcttc aacagccagccggcgaacccgggcaccaccgccacgtacctcgagggcaacatgctcatcaccagcgagagcgagacgcagc cggtgaaccgcgtggcgtacaacgtcggcgggcagatggccaccaacaaccagagctccaccactgcccccgcgaccggcacg tacaacctccaggaaatcgtgcccggcagcgtgtggatggagagggacgtgtacctccaaggacccatctgggccaagatcccag agacgggggcgcactttcacccctctccggccatgggcggattcggactcaaacacccaccgcccatgatgctcatcaagaacacg cctgtgcccggaaatatcaccagcttctcggacgtgcccgtcagcagcttcatcacccagtacagcaccgggcaggtcaccgtgga gatggagtgggagctcaagaaggaaaactccaagaggtggaacccagagatccagtacacaaacaactacaacgacccccagttt gtggactttgccccggacagcaccggggaatacagaaccaccagacctatcggaacccgataccttacccgacccctttaagctag cagctgatgcatagcatgcggtaccgggagatgggggaggctaactgaaacacggaaggagacaataccggaaggaacccgcg ctatgacggcaataaaaagacagaataaaacgcacgggtgttgggtcgtttgttcGAGTCATTTAAATACCGGTCT GGGCGAACAAACGATGCTCGCCTTCCAGAAAACCGAGGATGCGAACCACTTCAT CCGGGGTCAGCACCACCGGCAAGCGCCGCGACGGCCGAGGTCTTCCGATCTCCT GAAGCCAGGGCAGATCCGTGCACAGCACCTTGCCGTAGAAGAACAGCAAGGCC GCCAATGCCTGACGATGCGTGGAGACCGAAACCTTGCGCTCGTTCGCCAGCCAG GACAGAAATGCCTCGACTTCGCTGCTGCCCAAGGTTGCCGGGTGACGCACACCG TGGAAACGGATGAAGGCACGAACCCAGTTGACATAAGCCTGTTCGGTTCGTAAA CTGTAATGCAAGTAGCGTATGCGCTCACGCAACTGGTCCAGAACCTTGACCGAAC GCAGCGGTGGTAACGGCGCAGTGGCGGTTTTCATGGCTTGTTATGACTGTTTTTT TGTACAGTCTATGCCTCGGGCATCCAAGCAGCAAGCGCGTTACGCCGTGGGTCGA TGTTTGATGTTATGGAGCAGCAACGATGTTACGCAGCAGCAACGATGTTACGCAG CAGGGCAGTCGCCCTAAAACAAAGTTAGGTGGCTCAAGTATGGGCATCATTCGC ACATGTAGGCTCGGCCCTGACCAAGTCAAATCCATGCGGGCTGCTCTTGATCTTT TCGGTCGTGAGTTCGGAGACGTAGCCACCTACTCCCAACATCAGCCGGACTCCG ATTACCTCGGGAACTTGCTCCGTAGTAAGACATTCATCGCGCTTGCTGCCTTCGAC CAAGAAGCGGTTGTTGGCGCTCTCGCGGCTTACGTTCTGCCCAAGTTTGAGCAG CCGCGTAGTGAGATCTATATCTATGATCTCGCAGTCTCCGGCGAGCACCGGAGGC AGGGCATTGCCACCGCGCTCATCAATCTCCTCAAGCATGAGGCCAACGCGCTTGG TGCTTATGTGATCTACGTGCAAGCAGATTACGGTGACGATCCCGCAGTGGCTCTC TATACAAAGTTGGGCATACGGGAAGAAGTGATGCACTTTGATATCGACCCAAGTA CCGCCACCTAACAATTCGTTCAAGCCGAGATCGGCTTCCCGGCCGCGGAGTTGTT CGGTAAATTGTCACAACGCCGCGAATATAGTCTTTACCATGCCCTTGGCCACGCCC CTCTTTAATACGACGGGCAATTTGCACTTCAGAAAATGAAGAGTTTGCTTTAGCC ATAACAAAAGTCCAGTATGCTTTTTCACAGCATAACTGGACTGATTTCAGTTTACA ACTATTCTGTCTAGTTTAAGACTTTATTGTCATAGTTTAGATCTATTTTGTTCAGTTT AAGACTTTATTGTCCGCCCACACCCGCTTACGCAGGGCATCCATTTATTACTCAAat cggatcccgggcccgtcgactgcagaggcctgcatgcaagcttggcgtaatcatggtcatagctgtttcctgtgtgaaattgttatccg ctcacaattccacacaacatacgagccggaagcataaagtgtaaagcctggggtgcctaatgagtgagctaactcacattaattgcgt tgcgctcactgcccgctttccagtcgggaaacctgtcgtgccagctgcattaatgaatcggccaacgcgcggggagaggcggtttgc gtattgggcgctcttccgcttcctcgctcactgactcgctgcgctcggtcgttcggctgcggcgagcggtatcagctcactcaaaggc ggtaatacggttatccacagaatcaggggataacgcaggaaagaacatgtgagcaaaaggccagcaaaaggccaggaaccgtaa aaaggccgcgttgctggcgtttttccataggctccgcccccctgacgagcatcacaaaaatcgacgctcaagtcagaggtggcgaa acccgacaggactataaagataccaggcgtttccccctggaagctccctcgtgcgctctcctgttccgaccctgccgcttaccggata cctgtccgcctttctcccttcgggaagcgtggcgctttctcatagctcacgctgtaggtatctcagttcggtgtaggtcgttcgctccaag ctgggctgtgtgcacgaaccccccgttcagcccgaccgctgcgccttatccggtaactatcgtcttgagtccaacccggtaagacac gacttatcgccactggcagcagccactggtaacaggattagcagagcgaggtatgtaggcggtgctacagagttcttgaagtggtgg cctaactacggctacactagaagaacagtatttggtatctgcgctctgctgaagccagttaccttcggaaaaagagttggtagctcttga tccggcaaacaaaccaccgctggtagcggtggtttttttgtttgcaagcagcagattacgcgcagaaaaaaaggatctcaagaagatc ctttgatcttttctacggggtctgacgctcagtggaacgaaaactcacgttaagggattttggtcatgagattatcaaaaaggatcttcacctagatccttttaaattaaaaatgaagttttaaatcaatctaaagtatatatgagtaaacttggtctgacagttaccaatgcttaatcagtgag gcacctatctcagcgatctgtctatttcgttcatccatagttgcctgactccccgtcgtgtagataactacgatacgggagggcttaccat ctggccccagtgctgcaatgataccgcgagacccacgctcaccggctccagatttatcagcaataaaccagccagccggaagggc cgagcgcagaagtggtcctgcaactttatccgcctccatccagtctattaattgttgccgggaagctagagtaagtagttcgccagttaa tagtttgcgcaacgttgttgccattgctacaggcatcgtggtgtcacgctcgtcgtttggtatggcttcattcagctccggttcccaacga tcaaggcgagttacatgatcccccatgttgtgcaaaaaagcggttagctccttcggtcctccgatcgttgtcagaagtaagttggccgc agtgttatcactcatggttatggcagcactgcataattctcttactgtcatgccatccgtaagatgcttttctgtgactggtgagtactcaac caagtcattctgagaatagtgtatgcggcgaccgagttgctcttgcccggcgtcaatacgggataataccgcgccacatagcagaact ttaaaagtgctcatcattggaaaacgttcttcggggcgaaaactctcaaggatcttaccgctgttgagatccagttcgatgtaacccact cgtgcacccaactgatcttcagcatcttttactttcaccagcgtttctgggtgagcaaaaacaggaaggcaaaatgccgcaaaaaagg gaataagggcgacacggaaatgttgaatactcatactcttcctttttcaatattattgaagcatttatcagggttattgtctcatgagcggat acatatttgaatgtatttagaaaaataaacaaataggggttccgcgcacatttccccgaaaagtgccacctgacgtctaagaaaccatta ttatcatgacattaacctataaaaataggcgtatcacgaggccctttcgtc pB-40L-Rcp2Cap5 (SEQ ID NO: 47) tcgcgcgtttcggtgatgacggtgaaaacctctgacacatgcagctcccggagacggtcacagcttgtctgtaagcggatgccggga gcagacaagcccgtcagggcgcgtcagcgggtgttggcgggtgtcggggctggcttaactatgcggcatcagagcagattgtact gagagtgcaccatatgcggtgtgaaataccgcacagatgcgtaaggagaaaataccgcatcaggcgccattcgccattcaggctgc gcaactgttgggaagggcgatcggtgcgggcctcttcgctattacgccagctggcgaaagggggatgtgctgcaaggcgattaagt tgggtaacgccagggttttcccagtcacgacgttgtaaaacgacggccagtgaattcgagctcggtacctcgcgaatgcatctagat GATTAAAAACATAACAGGAAGAAAAATGCCCCGCTGTGGGCGGACAAAATAGTT GGGAACTGGGAGGGGTGGAAATGGAGTTTTTAAGGATTATTTAGGGAAGAGTGA CAAAATAGATGGGAACTGGGTGTAGCGTCGTAAGCTAATACGAAAATTAAAAATG ACAAAATAGTTTGGAACTAGATTTCACTTATCTGGTTcggatctgggtccccctaggctcaagcagt gatcagatccagacatgataagatacattgatgagtttggacaaaccacaactagaatgcagtgaaaaaaatgctttatttgtgaaattt gtgatgctattgctttatttgtaaccattataagctgcaataaacaagttaacaacaacaattgcattcattttatgtttcaggttcaggggga ggtgtgggaggttttttaaagcaagtaaaacctctacaaatgtggtatggctgattatgatcctctagtacttctcgacaagcttgtcgag actgcaggctctagagtcgacctgcaggcatgcaagcttgattcctcgagtttattgttcaaagatgcagtcatccaaatccacattgac cagatcgcaggcagtgcaagcgtctggcacctttcccatgatatgatgaatgtagcacagtttctgatacgcctttttgacgacagaaa cgggttgagattctgacacgggaaagcactctaaacagtctttctgtccgtgagtgaagcagatatttgaattctgattcattctctcgcat tgtctgcagggaaacagcatcagattcatgcccacgtgacgagaacatttgttttggtacctgtctgcgtagttgatcgaagcttccgcg tctgacgtcgatggctgcgcaactgactcgcgcacccgtttgggctcacttatatctgcgtcactgggggcgggtcttttcttggctcca ccctttttgacgtagaattcatgctccacctcaaccacgtgatcctttgcccaccggaaaaagtctttgacttcctgcttggtgaccttccc aaagtcatgatccagacggcgggtgagttcaaatttgaacatccggtcttgcaacggctgctggtgttcgaaggtcgttgagttcccgt caatcacggcgcacatgttggtgttggaggtgacgatcacgggagtcgggtctatctgggccgaggacttgcatttctggtccacgc gcaccttgcttcctccgagaatggctttggccgactccacgaccttggcggtcatcttcccctcctcccaccagatcaccatcttgtcga cacagtcgttgaagggaaagttctcattggtccagtttacgcacccgtagaagggcacagtgtgggctatggcctccgcgatgttggt cttcccggtagttgcaggcccaaacagccagatggtgttcctcttgccgaactttttcgtggcccatcccagaaagacggaagccgca tattggggatcgtacccgtttagttccaaaattttataaatccgattgctggaaatgtcctccacgggctgctggcccaccaggtagtcg ggggcggttttagtcaggctcataatctttcccgcattgtccaaggcagccttgatttgggaccgcgagttggaggccgcattgaagg agatgtatgaAgcctggtcctcctggatccactgcttctccgaggtaatccccttgtccacgagccacccgaccagctccatgtacct ggctgaagtttttgatctgatcaccggcgcgtcagaattgggattctgattctctttgttctgctcctgcgtctgcgacacgtgcgtcagat gctgcgccaccaaccgtttacgctccgtgagattcaaacaggcgcttaaatactgttctaaattagtccacgcccactggagctcagg ctgggttttggggagcaagtaattggggatgtagcactcgtccaccaccttgttcccgcctccggcgccgtttctggtctttgtgaccgc gaaccagtttggcaaagtcggctcgatcccgcggtaaattctctgaatcagtttttcgcgaatctgactcaggaaacgtcccaaaacta aggatttcaccccggtggtttccacgagcacgtgtaagtggaagtagctctctcccttctcaaattgcacaaagaaaagggcctccggggccttactcacacggcgccactccgtcagaaagtcgcgctgcagcttctcggccacggtcaggggtgcctgctcaatcagattcag atccaagtcagaatctggcggcaactcccactccttctcggccacccagttcacaaagctgtcagaaatgccgggcagatgctcgtc aaggtcgctggggaccttaatcacaatctcgtaaaaccccgccaTAAAATAGGTGGCGGTTTTTTAGGAGT TggcggcagatccgcgcccgatggtGCGGCCGCacggtatgaataatccggaatatttataggtttttttattacaaaactgtta cgaaaacagtaaaatacttatttatttgcgagatggttatcattttaattatctccatgatctattaatattcACGCGTcggagtatacgg acctttaattcaacccaacacaatatattatagttaaataagaattattatcaaatcatttgtatattaattaaaatactatactgtaaattacatt ttatttacaatcaatactagtaaaaggtaggttcaaccactgatgcctaggcacaccgaaacgactaaccctaattcttatcctttacttca ggcgcgcccggcttaagcgtacgaacttaaaaaaaaaaatcaaaTATTTTatgtcttttgttgatcaccctccagattggttggaag aagttggtgaaggtcttcgcgagtttttgggccttgaagcgggcccaccgaaaccaaaacccaatcagcagcatcaagatcaagccc gtggtcttgtgctgcctggttataactatctcggacccggaaacggtctcgatcgaggagagcctgtcaacagggcagacgaggtcg cgcgagagcacgacatctcgtacaacgagcagcttgaggcgggagacaacccctacctcaagtacaaccacgcggacgccgagt ttcaggagaagctcgccgacgacacatccttcgggggaaacctcggaaaggcagtctttcaggccaagaaaagggttctcgaacct tttggcctggttgaagagggtgctaagacggcccctaccggaaagcggatagacgaccactttccaaaaagaaagaaggctcgga ccgaagaggactccaagccttccacctcgtcagacgccgaagctggacccagcggatcccagcagctgcaaatcccagcccaac cagcctcaagtttgggagctgatacaatgtctgcgggaggtggcggcccattgggcgacaataaccaaggtgccgatggagtggg caatgcctcgggagattggcattgcgattccacgtggatgggggacagagtcgtcaccaagtccacccgaacctgggtgctgccca gctacaacaaccaccagtaccgagagatcaaaagcggctccgtcgacggaagcaacgccaacgcctactttggatacagcacccc ctgggggtactttgactttaaccgcttccacagccactggagcccccgagactggcaaagactcatcaacaactactggggcttcag accccggtccctcagagtcaaaatcttcaacattcaagtcaaagaggtcacggtgcaggactccaccaccaccatcgccaacaacct cacctccaccgtccaagtgtttacggacgacgactaccagctgccctacgtcgtcggcaacgggaccgagggatgcctgccggcct tccctccgcaggtctttacgctgccgcagtacggttacgcgacgctgaaccgcgacaacacagaaaatcccaccgagaggagcag cttcttctgcctagagtactttcccagcaagatgctgagaacgggcaacaactttgagtttacctacaactttgaggaggtgcccttcca ctccagcttcgctcccagtcagaacctcttcaagctggccaacccgctggtggaccagtacttgtaccgcttcgtgagcacaaataac actggcggagtccagttcaacaagaacctggccgggagatacgccaacacctacaaaaactggttcccggggcccatgggccga acccagggctggaacctgggctccggggtcaaccgcgccagtgtcagcgccttcgccacgaccaataggatggagctcgagggc gcgagttaccaggtgcccccgcagccgaacggcatgaccaacaacctccagggcagcaacacctatgccctggagaacactatg atcttcaacagccagccggcgaacccgggcaccaccgccacgtacctcgagggcaacatgctcatcaccagcgagagcgagacg cagccggtgaaccgcgtggcgtacaacgtcggcgggcagatggccaccaacaaccagagctccaccactgcccccgcgaccgg cacgtacaacctccaggaaatcgtgcccggcagcgtgtggatggagagggacgtgtacctccaaggacccatctgggccaagatc ccagagacgggggcgcactttcacccctctccggccatgggcggattcggactcaaacacccaccgcccatgatgctcatcaagaa cacgcctgtgcccggaaatatcaccagcttctcggacgtgcccgtcagcagcttcatcacccagtacagcaccgggcaggtcaccg tggagatggagtgggagctcaagaaggaaaactccaagaggtggaacccagagatccagtacacaaacaactacaacgaccccc agtttgtggactttgccccggacagcaccggggaatacagaaccaccagacctatcggaacccgataccttacccgacccctttaag ctagcagctgatgcatagcatgcggtaccgggagatgggggaggctaactgaaacacggaaggagacaataccggaaggaacc cgcgctatgacggcaataaaaagacagaataaaacgcacgggtgttgggtcgtttgttcGAGTCATTTAAATACCGG TCTGGGCGAACAAACGATGCTCGCCTTCCAGAAAACCGAGGATGCGAACCACTT CATCCGGGGTCAGCACCACCGGCAAGCGCCGCGACGGCCGAGGTCTTCCGATCT CCTGAAGCCAGGGCAGATCCGTGCACAGCACCTTGCCGTAGAAGAACAGCAAG GCCGCCAATGCCTGACGATGCGTGGAGACCGAAACCTTGCGCTCGTTCGCCAGC CAGGACAGAAATGCCTCGACTTCGCTGCTGCCCAAGGTTGCCGGGTGACGCACA CCGTGGAAACGGATGAAGGCACGAACCCAGTTGACATAAGCCTGTTCGGTTCGT AAACTGTAATGCAAGTAGCGTATGCGCTCACGCAACTGGTCCAGAACCTTGACC GAACGCAGCGGTGGTAACGGCGCAGTGGCGGTTTTCATGGCTTGTTATGACTGTT TTTTTGTACAGTCTATGCCTCGGGCATCCAAGCAGCAAGCGCGTTACGCCGTGGG TCGATGTTTGATGTTATGGAGCAGCAACGATGTTACGCAGCAGCAACGATGTTAC GCAGCAGGGCAGTCGCCCTAAAACAAAGTTAGGTGGCTCAAGTATGGGCATCAT TCGCACATGTAGGCTCGGCCCTGACCAAGTCAAATCCATGCGGGCTGCTCTTGAT CTTTTCGGTCGTGAGTTCGGAGACGTAGCCACCTACTCCCAACATCAGCCGGACT CCGATTACCTCGGGAACTTGCTCCGTAGTAAGACATTCATCGCGCTTGCTGCCTTCGACCAAGAAGCGGTTGTTGGCGCTCTCGCGGCTTACGTTCTGCCCAAGTTTGAG CAGCCGCGTAGTGAGATCTATATCTATGATCTCGCAGTCTCCGGCGAGCACCGGA GGCAGGGCATTGCCACCGCGCTCATCAATCTCCTCAAGCATGAGGCCAACGCGCT TGGTGCTTATGTGATCTACGTGCAAGCAGATTACGGTGACGATCCCGCAGTGGCT CTCTATACAAAGTTGGGCATACGGGAAGAAGTGATGCACTTTGATATCGACCCAA GTACCGCCACCTAACAATTCGTTCAAGCCGAGATCGGCTTCCCGGCCGCGGAGTT GTTCGGTAAATTGTCACAACGCCGCGAATATAGTCTTTACCATGCCCTTGGCCACG CCCCTCTTTAATACGACGGGCAATTTGCACTTCAGAAAATGAAGAGTTTGCTTTA GCCATAACAAAAGTCCAGTATGCTTTTTCACAGCATAACTGGACTGATTTCAGTTT ACAACTATTCTGTCTAGTTTAAGACTTTATTGTCATAGTTTAGATCTATTTTGTTCA GTTTAAGACTTTATTGTCCGCCCACACCCGCTTACGCAGGGCATCCATTTATTACT CAAatcggatcccgggcccgtcgactgcagaggcctgcatgcaagcttggcgtaatcatggtcatagctgtttcctgtgtgaaattg ttatccgctcacaattccacacaacatacgagccggaagcataaagtgtaaagcctggggtgcctaatgagtgagctaactcacatta attgcgttgcgctcactgcccgctttccagtcgggaaacctgtcgtgccagctgcattaatgaatcggccaacgcgcggggagaggc ggtttgcgtattgggcgctcttccgcttcctcgctcactgactcgctgcgctcggtcgttcggctgcggcgagcggtatcagctcactc aaaggcggtaatacggttatccacagaatcaggggataacgcaggaaagaacatgtgagcaaaaggccagcaaaaggccaggaa ccgtaaaaaggccgcgttgctggcgtttttccataggctccgcccccctgacgagcatcacaaaaatcgacgctcaagtcagaggtg gcgaaacccgacaggactataaagataccaggcgtttccccctggaagctccctcgtgcgctctcctgttccgaccctgccgcttacc ggatacctgtccgcctttctcccttcgggaagcgtggcgctttctcatagctcacgctgtaggtatctcagttcggtgtaggtcgttcgct ccaagctgggctgtgtgcacgaaccccccgttcagcccgaccgctgcgccttatccggtaactatcgtcttgagtccaacccggtaa gacacgacttatcgccactggcagcagccactggtaacaggattagcagagcgaggtatgtaggcggtgctacagagttcttgaagt ggtggcctaactacggctacactagaagaacagtatttggtatctgcgctctgctgaagccagttaccttcggaaaaagagttggtagc tcttgatccggcaaacaaaccaccgctggtagcggtggtttttttgtttgcaagcagcagattacgcgcagaaaaaaaggatctcaag aagatcctttgatcttttctacggggtctgacgctcagtggaacgaaaactcacgttaagggattttggtcatgagattatcaaaaaggat cttcacctagatccttttaaattaaaaatgaagttttaaatcaatctaaagtatatatgagtaaacttggtctgacagttaccaatgcttaatc agtgaggcacctatctcagcgatctgtctatttcgttcatccatagttgcctgactccccgtcgtgtagataactacgatacgggagggc ttaccatctggccccagtgctgcaatgataccgcgagacccacgctcaccggctccagatttatcagcaataaaccagccagccgga agggccgagcgcagaagtggtcctgcaactttatccgcctccatccagtctattaattgttgccgggaagctagagtaagtagttcgcc agttaatagtUgcgcaacgttgttgccaUgctacaggcatcgtggtgtcacgctcgtcgtttggtatggcttcattcagctccggttccc aacgatcaaggcgagttacatgatcccccatgttgtgcaaaaaagcggttagctccttcggtcctccgatcgttgtcagaagtaagttg gccgcagtgttatcactcatggttatggcagcactgcataattctcttactgtcatgccatccgtaagatgcttttctgtgactggtgagta ctcaaccaagtcattctgagaatagtgtatgcggcgaccgagttgctcttgcccggcgtcaatacgggataataccgcgccacatagc agaactttaaaagtgctcatcattggaaaacgttcttcggggcgaaaactctcaaggatcttaccgctgttgagatccagttcgatgtaa cccactcgtgcacccaactgatcttcagcatcttttactttcaccagcgtttctgggtgagcaaaaacaggaaggcaaaatgccgcaaa aaagggaataagggcgacacggaaatgttgaatactcatactcttcctttttcaatattattgaagcatttatcagggttattgtctcatgag cggatacatatttgaatgtatttagaaaaataaacaaataggggttccgcgcacatttccccgaaaagtgccacctgacgtctaagaaa ccattattatcatgacattaacctataaaaataggcgtatcacgaggccctttcgtc pB-40S-Rep2Cap5 (SEQ ID NO: 48) tcgcgcgtttcggtgatgacggtgaaaacctctgacacatgcagctcccggagacggtcacagcttgtctgtaagcggatgccggga gcagacaagcccgtcagggcgcgtcagcgggtgttggcgggtgtcggggctggcttaactatgcggcatcagagcagattgtact gagagtgcaccatatgcggtgtgaaataccgcacagatgcgtaaggagaaaataccgcatcaggcgccattcgccattcaggctgc gcaactgttgggaagggcgatcggtgcgggcctcttcgctattacgccagctggcgaaagggggatgtgctgcaaggcgattaagt tgggtaacgccagggttttcccagtcacgacgttgtaaaacgacggccagtgaattcgagctcggtacctcgcgaatgcatctagat GATTAAAAACATAACAGGAAGAAAAATGCCCCGCTGTGGGCGGACAAAATAGTT GGGAACTGGGAGGGGTGGAAATGGAGTTTTTAAGGATTATTTAGGGAAGAGTGA CAAAATAGATGGGAACTGGGTGTAGCGTCGTAAGCTAATACGAAAATTAAAAATG ACAAAATAGTTTGGAACTAGATTTCACTTATCTGGTTcggatctgggtccccctaggctcaagcagtgatcagatccagacatgataagatacattgatgagtttggacaaaccacaactagaatgcagtgaaaaaaatgctttatttgtgaaattt gtgatgctattgctttatttgtaaccattataagctgcaataaacaagttaacaacaacaattgcattcattttatgtttcaggttcaggggga ggtgtgggaggttttttaaagcaagtaaaacctctacaaatgtggtatggctgattatgatcctctagtacttctcgacaagcttgtcgag actgcaggctctagagtcgacctgcaggcatgcaagcttgattcctcgagtttattgttcaaagatgcagtcatccaaatccacattgac cagatcgcaggcagtgcaagcgtctggcacctttcccatgatatgatgaatgtagcacagtttctgatacgcctttttgacgacagaaa cgggttgagattctgacacgggaaagcactctaaacagtctttctgtccgtgagtgaagcagatatttgaattctgattcattctctcgcat tgtctgcagggaaacagcatcagattcatgcccacgtgacgagaacatttgttttggtacctgtctgcgtagttgatcgaagcttccgcg tctgacgtcgatggctgcgcaactgactcgcgcacccgtttgggctcacttatatctgcgtcactgggggcgggtcttttcttggctcca ccctttttgacgtagaattcatgctccacctcaaccacgtgatcctttgcccaccggaaaaagtctttgacttcctgcttggtgaccttccc aaagtcatgatccagacggcgggtgagttcaaatttgaacatccggtcttgcaacggctgctggtgttcgaaggtcgttgagttcccgt caatcacggcgcacatgttggtgttggaggtgacgatcacgggagtcgggtctatctgggccgaggacttgcatttctggtccacgc gcaccttgcttcctccgagaatggctttggccgactccacgaccttggcggtcatcttcccctcctcccaccagatcaccatcttgtcga cacagtcgttgaagggaaagttctcattggtccagtttacgcacccgtagaagggcacagtgtgggctatggcctccgcgatgttggt cttcccggtagttgcaggcccaaacagccagatggtgttcctcttgccgaactttttcgtggcccatcccagaaagacggaagccgca tattggggatcgtacccgtttagttccaaaattttataaatccgattgctggaaatgtcctccacgggctgctggcccaccaggtagtcg ggggcggttttagtcaggctcataatctttcccgcattgtccaaggcagccttgatttgggaccgcgagttggaggccgcattgaagg agatgtatgaAgcctggtcctcctggatccactgcttctccgaggtaatccccttgtccacgagccacccgaccagctccatgtacct ggctgaagtttttgatctgatcaccggcgcgtcagaattgggattctgattctctttgttctgctcctgcgtctgcgacacgtgcgtcagat gctgcgccaccaaccgtttacgctccgtgagattcaaacaggcgcttaaatactgttctaaattagtccacgcccactggagctcagg ctgggttttggggagcaagtaattggggatgtagcactcgtccaccaccttgttcccgcctccggcgccgtttctggtctttgtgaccgc gaaccagtttggcaaagtcggctcgatcccgcggtaaattctctgaatcagtttttcgcgaatctgactcaggaaacgtcccaaaacta aggatttcaccccggtggtttccacgagcacgtgtaagtggaagtagctctctcccttctcaaattgcacaaagaaaagggcctccgg ggccttactcacacggcgccactccgtcagaaagtcgcgctgcagcttctcggccacggtcaggggtgcctgctcaatcagattcag atccaagtcagaatctggcggcaactcccactccttctcggccacccagttcacaaagctgtcagaaatgccgggcagatgctcgtc aaggtcgctggggaccttaatcacaatctcgtaaaaccccgccaTAAAATAtttgatttttttttttaagttggcggcagatccgcg cccgatggtGCGGCCGCacggtatgaataatccggaatatttataggtttttttattacaaaactgttacgaaaacagtaaaatact tatttatttgcgagatggttatcattttaattatctccatgatctattaatattcACGCGTcggagtatacggacctttaattcaacccaac acaatatattatagttaaataagaattattatcaaatcatttgtatattaattaaaatactatactgtaaattacattttatttacaatcaatactag taaaaggtaggttcaaccactgatgcctaggcacaccgaaacgactaaccctaattcltatcctttacttcaggcgcgcccggcttaag cgtacgaacttaaaaaaaaaaatcaaaTATTTTatgtcttttgttgatcaccctccagattggttggaagaagttggtgaaggtcttc gcgagtttttgggccttgaagcgggcccaccgaaaccaaaacccaatcagcagcatcaagatcaagcccgtggtcttgtgctgcctg gttataactatctcggacccggaaacggtctcgatcgaggagagcctgtcaacagggcagacgaggtcgcgcgagagcacgacat ctcgtacaacgagcagcttgaggcgggagacaacccctacctcaagtacaaccacgcggacgccgagtttcaggagaagctcgcc gacgacacatccttcgggggaaacctcggaaaggcagtctttcaggccaagaaaagggttctcgaaccttttggcctggttgaagag ggtgctaagacggcccctaccggaaagcggatagacgaccactttccaaaaagaaagaaggctcggaccgaagaggactccaag ccttccacctcgtcagacgccgaagctggacccagcggatcccagcagctgcaaatcccagcccaaccagcctcaagtttgggag ctgatacaatgtctgcgggaggtggcggcccattgggcgacaataaccaaggtgccgatggagtgggcaatgcctcgggagattg gcattgcgattccacgtggatgggggacagagtcgtcaccaagtccacccgaacctgggtgctgcccagctacaacaaccaccagt accgagagatcaaaagcggctccgtcgacggaagcaacgccaacgcctactttggatacagcaccccctgggggtactttgacttta accgcttccacagccactggagcccccgagactggcaaagactcatcaacaactactggggcttcagaccccggtccctcagagtc aaaatcttcaacattcaagtcaaagaggtcacggtgcaggactccaccaccaccatcgccaacaacctcacctccaccgtccaagtg tttacggacgacgactaccagctgccctacgtcgtcggcaacgggaccgagggatgcctgccggccttccctccgcaggtctttacg ctgccgcagtacggttacgcgacgctgaaccgcgacaacacagaaaatcccaccgagaggagcagcttcttctgcctagagtacttt cccagcaagatgctgagaacgggcaacaactttgagtttacctacaactttgaggaggtgcccttccactccagcttcgctcccagtc agaacctcttcaagctggccaacccgctggtggaccagtacttgtaccgcttcgtgagcacaaataacactggcggagtccagttca acaagaacctggccgggagatacgccaacacctacaaaaactggttcccggggcccatgggccgaacccagggctggaacctgg gctccggggtcaaccgcgccagtgtcagcgccttcgccacgaccaataggatggagctcgagggcgcgagttaccaggtgcccc cgcagccgaacggcatgaccaacaacctccagggcagcaacacctatgccctggagaacactatgatcttcaacagccagccggc gaacccgggcaccaccgccacgtacctcgagggcaacatgctcatcaccagcgagagcgagacgcagccggtgaaccgcgtggcgtacaacgtcggcgggcagatggccaccaacaaccagagctccaccactgcccccgcgaccggcacgtacaacctccaggaa atcgtgcccggcagcgtgtggatggagagggacgtgtacctccaaggacccatctgggccaagatcccagagacgggggcgcac tttcacccctctccggccatgggcggattcggactcaaacacccaccgcccatgatgctcatcaagaacacgcctgtgcccggaaat atcaccagcttctcggacgtgcccgtcagcagcttcatcacccagtacagcaccgggcaggtcaccgtggagatggagtgggagct caagaaggaaaactccaagaggtggaacccagagatccagtacacaaacaactacaacgacccccagtttgtggactttgccccg gacagcaccggggaatacagaaccaccagacctatcggaacccgataccttacccgacccctttaagctagcagctgatgcatagc atgcggtaccgggagatgggggaggctaactgaaacacggaaggagacaataccggaaggaacccgcgctatgacggcaataa aaagacagaataaaacgcacgggtgttgggtcgtttgttcGAGTCATTTAAATACCGGTCTGGGCGAACA AACGATGCTCGCCTTCCAGAAAACCGAGGATGCGAACCACTTCATCCGGGGTCA GCACCACCGGCAAGCGCCGCGACGGCCGAGGTCTTCCGATCTCCTGAAGCCAGG GCAGATCCGTGCACAGCACCTTGCCGTAGAAGAACAGCAAGGCCGCCAATGCCT GACGATGCGTGGAGACCGAAACCTTGCGCTCGTTCGCCAGCCAGGACAGAAATG CCTCGACTTCGCTGCTGCCCAAGGTTGCCGGGTGACGCACACCGTGGAAACGGA TGAAGGCACGAACCCAGTTGACATAAGCCTGTTCGGTTCGTAAACTGTAATGCAA GTAGCGTATGCGCTCACGCAACTGGTCCAGAACCTTGACCGAACGCAGCGGTGG TAACGGCGCAGTGGCGGTTTTCATGGCTTGTTATGACTGTTTTTTTGTACAGTCTA TGCCTCGGGCATCCAAGCAGCAAGCGCGTTACGCCGTGGGTCGATGTTTGATGTT ATGGAGCAGCAACGATGTTACGCAGCAGCAACGATGTTACGCAGCAGGGCAGTC GCCCTAAAACAAAGTTAGGTGGCTCAAGTATGGGCATCATTCGCACATGTAGGCT CGGCCCTGACCAAGTCAAATCCATGCGGGCTGCTCTTGATCTTTTCGGTCGTGAG TTCGGAGACGTAGCCACCTACTCCCAACATCAGCCGGACTCCGATTACCTCGGGA ACTTGCTCCGTAGTAAGACATTCATCGCGCTTGCTGCCTTCGACCAAGAAGCGGT TGTTGGCGCTCTCGCGGCTTACGTTCTGCCCAAGTTTGAGCAGCCGCGTAGTGAG ATCTATATCTATGATCTCGCAGTCTCCGGCGAGCACCGGAGGCAGGGCATTGCCA CCGCGCTCATCAATCTCCTCAAGCATGAGGCCAACGCGCTTGGTGCTTATGTGAT CTACGTGCAAGCAGATTACGGTGACGATCCCGCAGTGGCTCTCTATACAAAGTTG GGCATACGGGAAGAAGTGATGCACTTTGATATCGACCCAAGTACCGCCACCTAAC AATTCGTTCAAGCCGAGATCGGCTTCCCGGCCGCGGAGTTGTTCGGTAAATTGTC ACAACGCCGCGAATATAGTCTTTACCATGCCCTTGGCCACGCCCCTCTTTAATACG ACGGGCAATTTGCACTTCAGAAAATGAAGAGTTTGCTTTAGCCATAACAAAAGTC CAGTATGCTTTTTCACAGCATAACTGGACTGATTTCAGTTTACAACTATTCTGTCT AGTTTAAGACTTTATTGTCATAGTTTAGATCTATTTTGTTCAGTTTAAGACTTTATT GTCCGCCCACACCCGCTTACGCAGGGCATCCATTTATTACTCAAatcggatcccgggcccgt cgactgcagaggcctgcatgcaagcttggcgtaatcatggtcatagctgtttcctgtgtgaaattgttatccgctcacaattccacacaa catacgagccggaagcataaagtgtaaagcctggggtgcctaatgagtgagctaactcacattaattgcgttgcgctcactgcccgct ttccagtcgggaaacctgtcgtgccagctgcattaatgaatcggccaacgcgcggggagaggcggtttgcgtattgggcgctcttcc gcttcctcgctcactgactcgctgcgctcggtcgttcggctgcggcgagcggtatcagctcactcaaaggcggtaatacggttatcca cagaatcaggggataacgcaggaaagaacatgtgagcaaaaggccagcaaaaggccaggaaccgtaaaaaggccgcgttgctg gcgtttttccataggctccgcccccctgacgagcatcacaaaaatcgacgctcaagtcagaggtggcgaaacccgacaggactata aagataccaggcgtttccccctggaagctccctcgtgcgctctcctgttccgaccctgccgcttaccggatacctgtccgcctttctccc ttcgggaagcgtggcgctttctcatagctcacgctgtaggtatctcagttcggtgtaggtcgttcgctccaagctgggctgtgtgcacg aaccccccgttcagcccgaccgctgcgccttatccggtaactatcgtcttgagtccaacccggtaagacacgacttatcgccactggc agcagccactggtaacaggattagcagagcgaggtatgtaggcggtgctacagagttcttgaagtggtggcctaactacggctacac tagaagaacagtatttggtatctgcgctctgctgaagccagttaccttcggaaaaagagttggtagctcttgatccggcaaacaaacca ccgctggtagcggtggtttttttgtttgcaagcagcagattacgcgcagaaaaaaaggatctcaagaagatcctttgatcttttctacgg ggtctgacgctcagtggaacgaaaactcacgttaagggattttggtcatgagattatcaaaaaggatcttcacctagatccttttaaatta aaaatgaagttttaaatcaatctaaagtatatatgagtaaacttggtctgacagttaccaatgcttaatcagtgaggcacctatctcagcg atctgtctatttcgttcatccatagttgcctgactccccgtcgtgtagataactacgatacgggagggcttaccatctggccccagtgctg caatgataccgcgagacccacgctcaccggctccagatttatcagcaataaaccagccagccggaagggccgagcgcagaagtggtcctgcaactttatccgcctccatccagtctattaattgttgccgggaagctagagtaagtagttcgccagttaatagtttgcgcaacgtt gttgccattgctacaggcatcgtggtgtcacgctcgtcgtttggtatggcttcattcagctccggttcccaacgatcaaggcgagttaca tgatcccccatgttgtgcaaaaaagcggttagctccttcggtcctccgatcgttgtcagaagtaagttggccgcagtgttatcactcatg gttatggcagcactgcataattctcttactgtcatgccatccgtaagatgcttttctgtgactggtgagtactcaaccaagtcattctgaga atagtgtatgcggcgaccgagttgctcttgcccggcgtcaatacgggataataccgcgccacatagcagaactttaaaagtgctcatc attggaaaacgttcttcggggcgaaaactctcaaggatcttaccgctgttgagatccagttcgatgtaacccactcgtgcacccaactg atcttcagcatcttttactttcaccagcgtttctgggtgagcaaaaacaggaaggcaaaatgccgcaaaaaagggaataagggcgac acggaaatgttgaatactcatactcttcctttttcaatattattgaagcatttatcagggttattgtctcatgagcggatacatatttgaatgtat ttagaaaaataaacaaataggggttccgcgcacatttccccgaaaagtgccacctgacgtctaagaaaccattattatcatgacattaa cctataaaaataggcgtatcacgaggccctttcgtcEQUIVALENTS
[0110] Those skilled in the art will recognize or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments of the invention described herein. The scope of the present invention is not intended to be limited to the above Description, but rather is as set forth in the following claims:
Claims
CLAIMSWe claim:
1. A nucleic acid molecule encoding adeno-associated virus (AAV) Cap wherein the nucleic acid molecule comprises: a 5’ UTR; and a modified Kozak sequence selected from SEQ ID NOs: 2-21.
2. The nucleic acid molecule of claim 1, wherein the modified Kozak sequence is attenuated.
3. The nucleic acid molecule of claim 2, wherein the attenuated Kozak sequence has a translation efficiency less than a wild type, or canonical Kozak sequence.
4. The nucleic acid molecule of claim 1, further comprising a translational enhancer sequence.
5. The nucleic acid molecule of claim 4, wherein the translational enhancer sequence is selected from Syn21 (SEQ ID NO: 25), L21 (SEQ ID NO: 26), AcNPV (SEQ ID NO: 27), EoNPV (SEQ ID NO: 28), TMV (SEQ ID NO: 29).
6. A method of producing recombinant AAV (rAAV) particles comprising transfecting the nucleic acid molecule of any one of claims 1-5 in a producer cell.
7. The method of claim 4, wherein the producer cell is an insect cell.
8. The method of claim 5, wherein the producer cell is Sf9 or a derivative cell line thereof.
9. The method of any one of claim 4-6, wherein the rAAV capsid is derived from AAV serotype 5 (AAV5).
10. A nucleic acid molecule encoding adeno-associated virus (AAV) Cap wherein the nucleic acid molecule comprises: a 5’ UTR; and a translational enhancer sequence selected from SEQ ID NOs: 25-29.
11. The nucleic acid molecule of claim 10, further comprising a modified Kozak sequence selected from SEQ ID NOs: 2-21.
12. A nucleic acid molecule encoding AAV Rep wherein the nucleic acid molecule comprises: a 5’ UTR; and a modified Kozak sequence selected from SEQ ID NOs: 2-21.
13. The nucleic acid molecule of claim 12, wherein the modified Kozak sequence is attenuated.
14. The nucleic acid molecule of claim 13, wherein the attenuated Kozak sequence has a translation efficiency less than a wild type, or canonical Kozak sequence.
15. The nucleic acid molecule of claim 12, further comprising a translational enhancer sequence.
16. The nucleic acid molecule of claim 15, wherein the translational enhancer sequence is selected from Syn21 (SEQ ID NO: 25), L21 (SEQ ID NO: 26), AcNPV (SEQ ID NO: 27), EoNPV (SEQ ID NO: 28), TMV (SEQ ID NO: 29).
17. The nucleic acid molecule of claim 12, wherein the modified Kozak sequence is SEQ ID NO. 8.
18. A nucleic acid molecule comprising a first nucleic acid sequence encoding AAV Cap wherein the first nucleic acid sequence comprises: a 5’ UTR; and a modified Kozak sequence selected from SEQ ID NOs: 2-21; and a second nucleic acid sequence encoding AAV Rep wherein the second nucleic acid sequence comprises: a 5’ UTR; and a modified Kozak sequence selected from SEQ ID NOs: 2-21.
19. The nucleic acid molecule of claim 18, wherein the first and / or second nucleic acid sequences further comprise a translational enhancer sequence selected from Syn21 (SEQ IDNO: 25), L21 (SEQ ID NO: 26), AcNPV (SEQ ID NO: 27), EoNPV (SEQ ID NO: 28), TMV (SEQ ID NO: 29).
20. A method of producing recombinant AAV (rAAV) particles comprising transfecting the nucleic acid molecule of any one of claims 12-17 in a producer cell.
21. The method of claim 20, wherein the producer cell is an insect cell.
22. The method of claim 21, wherein the producer cell is Sf9 or a derivative cell line thereof.
23. The method of any one of claim 20-22, wherein the rAAV Rep is derived from AAV serotype 2 (AAV2).
24. A method of producing recombinant AAV (rAAV) particles comprising transfecting the nucleic acid molecule of any one of claims 18 or 19 in a producer cell.
25. The method of claim 24, wherein the producer cell is Sf9 or a derivative cell line thereof.
26. The method of any one of claim 24 or 25, wherein the rAAV Rep is derived from AAV serotype 2 (AAV2).
27. The method of any one of claim 24 or 25, wherein the rAAV Cap is derived fromAAV serotype 5 (AAV5).