Improved norovirus vaccine sequences

Abstract

Codon-optimized nucleic acids encoding the Norovirus VP1 protein and their use are provided.

Description

Attorney Docket No. 090402-1544030-002710PCIMPROVED NOROVIRUS VACCINE SEQUENCESCROSS REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority benefit to U. S, Provisional Application No. 63 / 764,858, filed February 28, 2025, which is incorporated by reference in its entirety for all purposes.REFERENCE TO A SEQUENCE LISTING SUBMITTED AS XML FILE ATA EFS-WEB

[0002] The official copy of the sequence listing is submited electronically via EFS-Web as an.xml formatted sequence listing with a file named 090402-1544030-00271 OPC.xml, created on February 12, 2026, and having a size of 311,544 bytes, and is filed concurrently with the specification. The sequence listing contained in this.xml formatted document is part of the specification and is herein incorporated by reference in its entirety.BACKGROUND

[0003] Norovirus, also known as Norwalk virus, is the most common cause of gastroenteritis. The virus is highly contagious and thus is easily spread especially when people are in close proximity. Norovirus is review in for example, Robilotti E, Deresmski S, Pinsky BA 2015. Norovirus. Clin Microbiol Rev 28.BRIEF SUMMARY

[0004] In some embodiments, the disclosure provides a nucleic acid comprising a codon-altered coding sequence at least 85%, 90%, 95%, 98%, 99% or 100% identical to SEQ ID NO:3 or SEQ ID NO:5, wherein the coding sequence encodes a Norwalk GI.l ATI norovirus protein comprising SEQ ID NO: 9. In some embodiments, the nucleic acid comprises a first promoter operably linked to the coding sequence. In some embodiments, the first promoter comprises the CMV promoter or the SV40 promoter. In some embodiments, the first promoter is inducible. In some embodiments, the first promoter comprises a Tet operator.

[0005] In some embodiments, the nucleic acid is a vector. In some embodiments, the vector is a viral vector. In some embodiments, the viral vector is an adenoviral vector. In some embodiments, the adenoviral vector comprises a second promoter operably linked to a nucleic acid encoding atoll-like receptor-3 (TLR-3) agonist. In some embodiments, the TLR-3 agonist is a dsRNA. In some embodiments, the first promoter and the second promoter have different sequences. In some embodiments, the first promoter and second promoter are independently selected from a CMV promoter and an SV40 promoter. In some embodiments, the first promoter comprises a CMV promoter and the second promoter comprises an SV40 promoter. In some embodiments, the CMV promoter comprises a Tet operator, rendering the CMV promoter inducible.

[0006] Also provided is a nucleic acid comprising a codon-altered coding sequence at least 85%, 90%, 95%, 98%, 99% or 100% identical to SEQ ID NO:4 or SEQ ID NO:6, wherein the coding sequence encodes a Sydney GIL 4 VP1 norovirus protein comprising SEQ ID NO: 10. In some embodiments, the nucleic acid comprises a first promoter operably linked to the coding sequence. In some embodiments, the first promoter comprises the CMV promoter or the SV40 promoter. In some embodiments, the first promoter is inducible. In some embodiments, the first promoter comprises a Tet operator.

[0007] In some embodiments, the nucleic acid is a vector. In some embodiments, the vector is a viral vector. In some embodiments, the viral vector is an adenoviral vector. In some embodiments, the adenoviral vector comprises a second promoter operably linked to a nucleic acid encoding a toll-like receptor-3 (TLR-3) agonist. In some embodiments, the TLR-3 agonist is a dsRNA.

[0008] In some embodiments, the first promoter and the second promoter have different sequences. In some embodiments, the first promoter and second promoter are independently selected from a C V promoter and an SV40 promoter. In some embodiments, the first promoter comprises a CMV promoter and the second promoter comprises an SV40 promoter. In some embodiments, the CMV promoter comprises a Tet operator, rendering the CMV promoter inducible.

[0009] Also provided is a nucleic acid comprising a codon-altered coding sequence at least 85%, 90%, 95%, 98%, 99% or 100% identical to SEQ ID NO:7 or SEQ ID NO:8, wherein the coding sequence encodes a GII.17 VP1 norovirus protein comprising SEQ ID NO:11. In some embodiments, the nucleic acid comprises a first promoter operably linked to the coding sequence. In some embodiments, the first promoter comprises the CMV promoter or the SV40 promoter. In some embodiments, the first promoter is inducible. In some embodiments, the first promoter comprises a Tet operator.7

[0010] In some embodiments, the nucleic acid is a vector. In some embodiments, the vector is a viral vector. In some embodiments, the viral vector is an adenoviral vector. In some embodiments, the adenoviral vector comprises a second promoter operably linked to a nucleic acid encoding a toll-like receptor-3 (TLR-3) agonist. In some embodiments, the TLR-3 agonist is a dsRNA.

[0011] In some embodiments, the first promoter and the second promoter have different sequences. In some embodiments, the first promoter and second promoter are independently selected from a CMV promoter and an SV40 promoter. In some embodiments, the first promoter comprises a CMV promoter and the second promoter comprises an SV40 promoter. In some embodiments, the CMV promoter comprises a Tet operator, rendering the CMV promoter inducible.

[0012] Also provided is a method for eliciting an immune response towards a Norovirus VP1 protein in a subject. In some embodiments, the method comprises administering to the subject an immunogenically effective amount of one or more of the nucleic acids described above or elsewhere herein to a mammalian subject. In some embodiments, the administering is oral, intranasal, or mucosal. In some embodiments, the administering is oral delivery by swallowing a tablet or capsule. In some embodiments, the immune response is elicited in an alveolar cell, an absorptive enterocyte, a ciliated cell, a goblet cell, a club cell, a dendritic cell, a macrophage, and / or an airway basal cell of the subject. In some embodiments, the subject is a human,

[0013] Also provided is a pharmaceutical compositi on comprising one or more of the vectors as described above or elsewhere herein. In some embodiments, the pharmaceutical composition is a tablet or a capsule.DEFINITIONS

[0014] The term “chimeric” or “recombinant” as used herein with reference, e.g., to a nucleic acid, protein, or vector, indicates that the nucleic acid, protein or vector, has been modified by the introduction of a heterologous nucleic acid or protein or the alteration of a native nucleic acid or protein. Thus, for example, chimeric and recombinant vectors include nucleic acid sequences that are not found within the native (non-chimeric or non-recombmant) form of the vector. A chimeric adenoviral expression vector refers to an adenoviral expression vector comprising a nucleic acid sequence encoding a heterologous polypeptide, such as a norovirus protein.

[0015] The term “expression vector” refers to a nucleic acid construct, generated recombinantly or synthetically, with a senes of specified nucleic acid elements that permit transcription of a particular nucleic acid in a host cell. The expression vector can be part of a plasmid, virus, or nucleic acid fragment. Typically, the expression vector includes a nucleic acid to be transcribed operably linked to a promoter.

[0016] The term “promoter” refers to an array of nucleic acid control sequences that direct transcription of a nucleic acid. As used herein, a promoter includes necessary' nucleic acid sequences near the start site of transcription, such as, in the case of a polymerase II type promoter, a TATA element. A promoter also optionally includes distal enhancer or repressor elements, which can be located as many as several thousand base pairs from the start site of transcription. Promoters include constitutive and inducible promoters. A “constitutive” promoter is a promoter that is active under most environmental and developmental conditions. An “inducible” promoter is a promoter that is active under environmental or developmental regulation. The term “operably linked” refers to a functional linkage between a nucleic acid expression control sequence (such as a promoter, or array of transcription factor binding sites) and a second nucleic acid sequence, wherein the expression control sequence directs transcription of the nucleic acid corresponding to the second sequence.

[0017] The term “norovirus” refers to a smgle-stranded positive-sense RNA, non-enveloped viruses belonging to the family Caliciviridae. A number of genogroups and genotypes of norovirus have been described. See, e.g., Chhabra, et al., J Gen Virol. 2019 Sep 4;100(l 0): 1393— 1406; Chhabra, et al., J Gen Virol. 2019;100:1393-406. The norovirus genome contains 3 open reading frames (ORFs): ORFl encodes a polyprotein cleaved into 6 nonstructural proteins, including RNA-dependent RNA polymerase (RdRp); ORF2 encodes major (VP1) and ORF3 minor (VP2) capsid proteins (2). Noroviruses can be grouped into 10 genogroups (GI-GX) and 49 genotypes based on VP1 sequences. See, e.g., Ao, et al., Emerg Infect Dis. 2023;29(9):1837-1841. A new norovirus strain, GII.4 Sydney, was originally identified in Australia. See, e.g., Leshem, et al., Emerg Infect Dis. 2013 Aug;19(8): 1231-8. An earlier strain of norovirus was identified in people from Norwalk, Ohio, and is called the “Norwalk” strain.

[0018] The term “TLR agonist” or “Toll-like receptor agonist” as used herein refers to a compound that binds and stimulates a Toll-like receptor including, e.g., TLR-2, TLR-3, TLR-6,TLR-7, or TLR-8. TLR agonists are reviewed in MacKichan, IAVI Report. 9: 1-5 (2005) and Abreu et al., J Immunol, 174(8), 4453-4460 (2005). Agonists induce signal transduction following binding to their receptor.

[0019] The term “TLR- 3 agonist” or “Toll-like receptor 3 agonist” as used herein refers to a compound that binds and stimulates the TLR-3. TLR- 3 agonists have been identified including double-stranded RNA, virally derived dsRNA, several chemically synthesized analogs to double¬ stranded RNA including polyinosine-polycytidylic acid (poly EC) -polyadenylic-polyuridylic acid (poly A: U) and poly Lpoly C, and antibodies (or cross-linking of antibodies) to TLR-3 that lead to IFN-beta production (Matsumoto, M, et al, Biochem Biophys Res Commun 24:1364 (2002), de Bouteiller, et al, J Biol Chem 18:38133-45 (2005)). In some embodiments, a TLR-3 agonist comprises a sequence of any one of SEQ ID NOS: 12-20. In some embodiments, a TLR-3 agonist is a dsRNA (e.g, dsRNA encoded by a nucleic acid comprising a sequence set forth in SEQ ID NOs:12).

[0020] The term “heterologous” when used with reference to portions of a nucleic acid indicates that the nucleic acid comprises two or more subsequences that are not found in the same relationship to each other in nature. For instance, the nucleic acid is typically recombinantly produced, having two or more sequences from unrelated genes arranged to make a new functional nucleic acid, e.g., a promoter from one source and a coding region from another source. Similarly, a heterologous protein indicates that the protein comprises two or more subsequences that are not found in the same relationship to each other in nature (e.g., a fusion protein).

[0021] The terms “nucleic acid” and “polynucleotide” are used interchangeably herein to refer to deoxyribonucleotides or ribonucleotides and polymers thereof in either single- or double¬ stranded form. The term encompasses nucleic acids containing known nucleotide analogs or modified backbone residues or linkages, which are synthetic, naturally occurring, and non-naturally occurring, which have similar binding properties as the reference nucleic acid, and which are metabolized in a manner similar to the reference nucleotides. Examples of such analogs include, without limitation, phosphorothioates, phosphoramidates, methyl phosphonates, chiral-methyl phosphonates, 2-O-methyl ribonucleotides, peptide-nucleic acids (PNAs).

[0022] Unless otherwise indicated, a particular nucleic acid sequence also encompasses conservatively modified variants thereof (e.g., degenerate codon substitutions) and complementarysequences, as well as the sequence explicitly indicated. Specifically, degenerate codon substitutions may be achieved by generating sequences in which the third position of one or more selected (or all) codons is substituted with mixed-base and / or deoxymosine residues (Batzer etal., Nucleic Acid Res. 19:5081 (1991); Ohtsukaeta / ., J. Biol. Chem. 260:2605-2608 (1985); Rossolini etal., Mol. Cell. Probes 8:91-98 (1994)). The term nucleic acid is used interchangeably with gene, cDNA, mRNA, oligonucleotide, and polynucleotide.

[0023] The term “antigen” refers to a protein or part of a polypeptide chain that can be recognized by T cell receptors and / or antibodies. Typically, antigens are derived from bacterial, viral, or fungal proteins.

[0024] The term "immunogenically effective dose or amount” of the compositions of the present disclosure is an amount that elicits or modulates an immune response specific for the norovirus VP1 protein. Immune responses include humoral immune responses and cell-mediated immune responses. An immunogenic composition can be used therapeutically or prophylactically to treat or prevent disease at any stage. Humoral immune responses are generally mediated by cell free components of the blood, i.e., plasma or serum; transfer of the serum or plasma from one individual to another transfers immunity. Cell mediated immune responses are generally mediated by antigen specific lymphocytes; transfer of the antigen specific lymphocytes from one individual to another transfers immunity,

[0025] The term “therapeutic dose” or “therapeutically effective amount” or “effective amount” of a chimeric adenoviral vector or a composition comprising a chimeric adenoviral vector refers to an amount of the vector or composition comprising the vector which prevents, alleviates, abates, or reduces the severity of symptoms of diseases and disorders associated with the source of the norovirus protein (e.g., a norovirus).

[0026] The term “adjuvant” refers to a non-specific immune response enhancer. Suitable adjuvants include, for example, cholera toxin, monophosphoryl lipid A (MPL), Freund’s Complete Adjuvant, Freund’s Incomplete Adjuvant, Quil A, and Al(C)H). Adjuvants can also be those substances that cause antigen-presenting cell activation and enhanced presentation of T cells through secondary signaling molecules like Toll-like receptors. Examples of Toll-like receptors include the receptors that recognize double-stranded RNA, bacterial flagella, EPS, CpG DNA, and bacterial lipopeptide (Reviewed recently in Abreu etal., J Immunol, 174(8), 4453-4460 (2005)).

[0027] The terms “polypeptide,” “peptide,” and “protein” are used interchangeably herein to refer to a polymer of amino acid residues. The terms apply to amino acid polymers in which one or more amino acid residue is an artificial chemical mimetic of a corresponding naturally occurring amino acid, as well as to naturally occurring amino acid polymers and non-naturally occurring amino acid polymer.

[0028] The term “amino acid” refers to naturally occurring and synthetic amino acids, as well as amino acid analogs and amino acid mimetics that function in a manner similar to the naturally occurring amino acids. Naturally occurring amino acids are those encoded by the genetic code, as well as those amino acids that are later modified, e.g., hydroxyproline and 0-phosphosenne. Ammo acid analog refers to compounds that have the same basic chemical structure as a naturally occurring ammo acid, i.e., an a carbon that is bound to a hydrogen, a carboxyl group, an amino group, and an R group, e.g., homoserine, norleucine, methionine sulfoxide, methionine methyl sulfonium. Such analogs have modified R groups (e.g., norleucine) or modified peptide backbones, but retain the same basic chemical structure as a naturally occurring amino acid. Amino acid mimetics refers to chemical compounds that have a structure that is different from the general chemical structure of an amino acid, but that functions in a manner similar to a naturally occurring ammo acid.

[0029] Amino acids may be referred to herein by either their commonly known three letter symbols or by the one-letter symbols recommended by the TUPAC -TUB Biochemical Nomenclature Commission. Nucleotides, likewise, may be referred to by their commonly accepted single-letter codes.

[0030] As used herein, the term "percent identity" or "percent identical," used in the context of nucleic acids or polypeptides, refers to a sequence that has at least 50% sequence identity with a reference sequence (e.g., SEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, or 28 or any other sequences provided herein). / Xlternatively, percent identity can be any integer from 50% to 100%. In some embodiments, a sequence is substantially identical to a reference sequence if the sequence has at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the reference sequence as determined using the methods described herein; preferably BLAST usingstandard parameters, as described below. Percent identity may also be determined by manual alignment.

[0031] For sequence comparison, typically one sequence acts as a reference sequence, to which test sequences are compared. When using a sequence comparison algorithm, test and reference sequences are entered into a computer, subsequence coordinates are designated, if necessary, and sequence algorithm program parameters are designated. Default program parameters can be used, or alternative parameters can be designated. The sequence comparison algorithm then calculates the percent sequence identities for the test sequences relative to the reference sequence, based on the program parameters.

[0032] A comparison window includes reference to a segment of any one of the number of contiguous positions, e.g., a segment of at least 10 residues. In some embodiments, the comparison window has from 10 to 600 residues, e.g., about 10 to about 30 residues, about 10 to about 20 residues, about 50 to about 200 residues, or about 100 to about 150 residues, in which a sequence may be compared to a reference sequence of the same number of contiguous positions after the two sequences are optimally aligned.

[0033] Algorithms that are suitable for determining percent sequence identity and sequence similarity are the BLAST and BLAST 2.0 algorithms, which are described in Altschul etal. (1990) J. Mol. Biol. 215: 403-410 and Altschul et al, (1977) Nucleic Adds Res. 25: 3389-3402, respectively. Software for performing BLAST analyses is publicly available through the National Center for Biotechnology Information (NCBI) web site. The algorithm involves first identifying high scoring sequence pairs (HSPs) by identifying short words of l ength W in the query sequence, which either match or satisfy some positive-valued threshold score T when aligned with a word of the same length in a database sequence. T is referred to as the neighborhood word score threshold (Altschul etal, supra. These initial neighborhood word hits act as seeds for initiating searches to find longer HSPs containing them. The word hits are then extended in both directions along each sequence for as far as the cumulative alignment score can be increased. Cumulative scores are calculated using, for nucleotide sequences, the parameters M (reward score for a pair of matching residues; always >0) and N (penalty score for mismatching residues; always <0). For amino acid sequences, a scoring matrix is used to calculate the cumulative score. Extension of the word hits in each direction are halted when: the cumulative alignment score falls off by the quantity X fromits maximum achieved value; the cumulative score goes to zero or below, due to the accumulation of one or more negative-scoring residue alignments: or the end of either sequence is reached. The BLAST algorithm parameters W, T, and X determine the sensitivity and speed of the alignment. The BLASTN program (for nucleotide sequences) uses as defaults a word size (W) of 28, an expectation (E) of 10, M=l, N=-2, and a comparison of both strands. For amino acid sequences, the BLASTP program uses as defaults a word size (W) of 3, an expectation (E) of 10, and the BLOSUM62 scoring matrix (see Henikoff & Henikoff, Proc. Natl. Acad. Sci. USA 89:10915 (1989)).

[0034] The BLAST algorithm also performs a statistical analysis of the similarity between two sequences (see, e.g., Karlin & Altschul, Proc. Nat'l. Acad. Sci. USA 90:5873-5787 (1993)). One measure of similarity provided by the BLAST algorithm is the smallest sum probability' (P(N)), which provides an indication of the probability by which a match between two nucleotide or amino acid sequences would occur by chance. For example, an amino acid sequence is considered similar to a reference sequence if the smallest sum probability in a comparison of the test ammo acid sequence to the reference ammo acid sequence is less than about 0,01, more preferably less than about 10'5, and most preferably less than about IO'20.

[0035] “Codon-altered” coding sequences have at least one change from a natural coding sequence such that the codon-altered coding sequence has higher expression than the natural coding sequence in a particular cell, e.g., a human intestinal epithelial cells (e.g,, HIEC-6 cells).BRIEF DESCRIPTION OF THE. DRAWINGS

[0036] The present application includes the following figures. The figures are intended to illustrate certain embodiments and / or features of the compositions and methods, and to supplement any description(s) of the compositions and methods. The figures do not limit the scope of the compositions and methods, unless the written description expressly indicates that such is the case.

[0037] FIG. 1A show's a schematic of GI.l vectors. FIG. IB show's relative VP1 protein expression of the vectors indicated in HIEC-6 cells.

[0038] FIG. 2A show's a schematic of GII.4 vectors. FIG. 2B shows relative VP1 protein expression of the vectors indicated in HIEC-6 cells.

[0039] FIG. 3 shows serum IgG levels specific for GI.l VP1 in mice following the indicated dose of adenoviral constructs EDI 50 and CS186.

[0040] FIG 4 shows serum IgG levels specific for GIL 4 VP1 in mice following the indicated dose of adenoviral constructs EDI 53 and ED11.

[0041] FIG 5 shows a schematic of the vaccination and sample collection schedule in hamsters.

[0042] FIGs. 6A and 6B show serum anti-GI.1 VP1 IgG and IgA levels, respectively, in hamsters following administration of adenoviral CS186 or EDI 50 constructs.

[0043] FIGs. 7A and 7B show serum anti-GII.4 VP1 IgG and IgA levels, respectively, in hamsters following administration of adenoviral EDI 1 or EDI 53 constructs.

[0044] FIGs. 8A and 8B show fecal anti-GI.1 VP1 IgA and anti-GII.4 VP1 IgA levels, respectively, in hamsters following administration of adenoviral CS186 or EDI 50 constructs (Panel A) or following administration of adenoviral constructs EDI 1 and EDI 53 (Panel B).

[0045] FIGs. 9A and 9B show salivary anti-GI.l VP1 IgA and anti-GII.4 VP1 IgA levels, respectively, in hamsters following administration of adenoviral CS186 or EDI 50 constructs (Panel A) or following administration of adenoviral constructs EDI 1 and EDI 53 (Panel B).

[0046] FIGs. 10A and 10B show GI.l VP1 norovirus blocking antibody assay (NBAA) titers (Panel A) and fold increases (Panel B) at day 28 post-treatment in clinical trial participants following the indicated dose of adenoviral CS186 and EDI 1 or ED150 and ED153 constructs.

[0047] FIGs. 11A and 11B show GII.4 VP1 norovirus blocking antibody assay (NBAA) titers (Panel A) and fold increases (Panel B) at day 28 post-treatment in clinical trial participants following the indicated dose of adenoviral CS186 and ED11 or EDI 50 and EDI 53 constructs.

[0048] FIGs. 12A and 12B show fold rise in fecal GI.1 IgA (Panel A) or fecal GII.4 IgA (Panel B) at days 0, 28, and 179 post-treatment in clinical trial participants following the indicated dose of adenoviral CS186 and EDI 1 or EDI 50 and EDI 53 constructs.

[0049] FIGs. 13A and 13B show fluorescent microscopy imaging of VP1 protein expression in differentiated ileum enteroid cultures following transduction with adenoviral EDI 1 (A) and EDI 53 (B) constructs.

[0050] FIGs. 14A and 14B show GI. l VP1 expression in human intestinal organoid monolayers following transduction with adenoviral CS186, EDU (Panel A) and GII.4 VP1 expression in human intestinal organoid monolayers following transduction with adenoviral EDI 50, or ED 153 constructs (Panel B).DETAILED DESCRIPTION

[0051] The following description recites various aspects and embodiments of the present compositions and methods. No particular embodiment is intended to define the scope of the compositions and methods. Rather, the embodiments merely provide non-limiting examples of various compositions and methods that are at least included within the scope of the disclosed compositions and methods. The description is to be read from the perspective of one of ordinary skill in the art; therefore, information well known to the skilled artisan is not necessarily included.

[0052] VP1 is the major capsid protein of norovirus. See, e.g., Ao, et al., Emerg Infect Dis.2023;29(9): 1837-1841. A number of variants of the VP1 protein are known, including the Norwalk GI.1 VP1 protein (SEQ ID NO: 9), the Sydney GII.4 VP1 protein (SEQ ID NO: 10) and the GIL 17 VP1 protein (SEQ ID NO: 11). The present disclosure provides for optimized coding sequences for SEQ ID NO: 9, SEQ ID NO: 10 and SEQ ID NO: 11, which are useful for expression of these VP1 proteins, e.g,, in human cells. For example, SEQ ID NOs: 3 and 5 are codon-optimized sequences that encode the Norwalk GI.l VP1 protein (SEQ ID NO: 9) and result in high expression of the protein, e g., higher than to a previous codon-optimized coding sequence (SEQ ID NO: 1), SEQ ID NOs: 4 and 6 are codon-optimized sequences that encode the Sydney GII.4 VP1 protein (SEQ ID NO: 10) and result in high expression of the protein, e.g., higher than to a previous codon -optimized coding sequence (SEQ ID NO:2). Moreover, SEQ ID NOs: 7 and 8 each are codon-optimized sequences that encode the GIL 17 VP1 protein (SEQ ID NO: 11) and result in high expression of the protein. Provided herein are, e.g., nucleic acid for protein expression in vitro or in vivo, nucleic acid vaccines, and methods for preventing or treating norovirus that involve the use of one or more nucleic acids that encode the norovirus VP1 proteins as described herein, optionally in an adenoviral vector, optionally further comprises a nucleic acid encoding a TLR-3 agonist.

[0053] The disclosure provides compositions comprising chimeric adenoviral vectors comprising one or more nucleic acids encoding one or more of the norovirus VP1 proteinsdescribed herein, wherein one of the nucleic acids comprises a codon-optimized polynucleotide as described herein encoding the VP1 protein. While exemplary’ VP1 protein coding sequences are SEQ ID NO:3, 4, 5, 6, 7, or 8, each of which were designed with the same codon optimization algorithm, in some embodiments, a norovirus \T1 protein coding sequence can be for example, a polynucleotide encoding the VP1 protein (e.g., SEQ ID NO:9, 10, or 11) and being at least 90, 91, 92, 93, 94, 95, 96, 97, 98, 99 or 100% identical to SEQ ID NO: 3, 4, 5, 6, 7, or 8. The chimeric adenoviral vectors can also include a nucleic acid encoding a toll-like receptor (TLR) agonist (e.g., a TLR-3 agonist), which can serve as an effective adjuvant when administered in conjunction with viral vectors. In some embodiments, the adenoviral vector is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, 99 or 100% identical to SEQ ID NO: 23 or SEQ ID NO: 25 (encoding SEQ ID NO: 9, optionally with a coding sequence at least 90, 91, 92, 93, 94, 95, 96, 97, 98, 99 or 100% identical to SEQ ID NO:3 or SEQ ID NO:5) or at least 90, 91, 92, 93, 94, 95, 96, 97, 98, 99 or 100% identical to SEQ ID NO: 24, or SEQ ID NO:26 (encoding SEQ ID NO: 10, optionally with a coding sequence at least 90, 91, 92, 93, 94, 95, 96, 97, 98, 99 or 100% identical to SEQ ID NO:4 or SEQ ID NO:6). In other embodiments, the disclosure provides for the VP1 coding sequences provided herein in any format useful for protein expression, which can be in vitro (e.g., cell-free expression or expression and optionally secretion from cells) or for in vivo expression (e.g., a nucleic acid delivered to a human wherein the expression occurs in one or more cells of the human).

[0054] While an attenuated adenovirus as described herein can be used to express a norovirus VP1 protein in a human, other polynucleotides or vectors can also be used. Expression vectors can include, for example, virally-derived vectors, e.g., recombinant adeno-associated virus (A / XV) vectors, retroviral vectors, adenoviral vectors, modified vaccinia Ankara (MV A) vectors, and lentiviral (e.g., I ISV-1 -derived) vectors (see, e.g., Brouardet# / . (2009) British J. Pharm. 157:153). In other embodiments, the norovirus VP1 protein can be encoded by a polynucleotide, e.g., naked or encapsulated DNA or RNA, e.g., mRNA (see, e.g., U. S. Patent Publication No. 2020 / 0254086 for details of various aspects for RNA-based vaccines).

[0055] In some embodiments, a norovirus VP1 protein coding sequence as described herein is present in an adenoviral vector, for example an adenovirus 5 (Ad5), which can include, for example, Ad5 with deletions of the E1 / E3 regions and Ad5 with a deletion of the E4 region. Other suitable adenoviral vectors include but are not limited to strains 2, orally tested strains 4 and 7,enteric adenoviruses 40 and 41, and other strains (e.g. Ad34) that are sufficient for delivering an antigen and eliciting an adaptive immune response to the transgene antigen (Lubeck et al., Proc Natl Acad Sci U SA, 86(17), 6763-6767 (1989); Shen et al., J Virol, 75(9), 4297-4307 (2001); Bailey etal., Virology, 202(2), 695-706 (1994)). In some embodiments, the adenoviral vector is a live, replication incompetent adenoviral vector (such as El and E3 deleted rAd5), live and attenuated adenoviral vector (such as the E1B55K deletion viruses), or a live adenoviral vector with wild-type replication.

[0056] In some embodiments an expression cassette comprising a promoter operably linked to the VPl-coding sequence described herein can be inserted in the adenoviral vector, e.g., in the location from which E1A was deleted, and inserted upstream of the adenoviral pIX coding sequence. The ElA-deleted Ad5 is a vector that is widely used, and a transgene cassette is frequently placed in this location. See, e.g., Hitt and Graham, Advances in Virus Research, Volume 55, 2000, Pages 479-505. Removal of one or more, optionally all, AG splice acceptor sites from the end of the expression cassette introduced into the adenoviral vector and from the beginning of the coding sequence of pIX is provided can in some embodiments increase expression. As an example, in adenoviral Adv5 viruses the sequence just upstream of the pIX coding sequence is the sequence GTTTTGCAGC'AGCCGCCXiCCGCC (SEQ ID N():29), where two AG splice acceptor sites are shown by underlining. In some embodiments, the adenoviral vectors provided herein can include this sequence, but wherein each of the two underlined? XG dinucleotide sequences are changed. Changing of an? XG dinucleotide can comprise changing the A or G or both to a different nucleotide. This for example, the “A” in an AG dinucleotide can be changed to a C, G, or T, and / or the “G” in the AG dinucleotide can be changed to A, C, or T, any of which change the “AG” to a non- AG sequence. In embodiments in which more than one AG dinucleotide sequence is disrupted, the different AG dinucleotides can be disrupted by the same change (merely as an example, both As changes to Cs) or each AG can be changed in a different manner (again merely as an example, a first AG disrupted by changing the A to a C and a second AG disrupted by for example changing the A to a T or changing the G to a C). Thus in some embodiments, an adenoviral expression vector is provided comprising at least a first expression cassette comprising a first promoter operably linked to a codon-optimized nucleic acid encoding a norovirus VP1 protein (e.g., a sequence at least 90, 91, 92, 93, 94, 95, 96, 97, 98, 99 or 100% identical to SEQ ID NO:3, 4, 5, 6, 7, or 8), and optionally a second expression cassette encoding a TLR-3 agonist as described herein; a nucleicacid encoding an adenovirus pIX protein; and a polynucleotide between the expression cassette and the nucleic acid encoding the pIX protein, wherein the polynucleotide is free of canonical splice acceptors comprising an AG dinucleotide sequence.

[0057] The transcriptional and translational control sequences m expression vectors to be used in transforming vertebrate cells in vivo may be provided by viral sources. For example, commonly used promoters and enhancers are derived, e.g., from beta-actin, adenovirus, simian virus (SV40), and human cytomegalovirus (CMV). For example, vectors allowing expression of proteins under the direction of the CMV promoter, beta-actin promoter, SV40 early promoter, SV40 later promoter, metallothionein promoter, murine mammary tumor virus promoter, Rous sarcoma virus promoter, transducer promoter, or other promoters shown effective for expression in mammalian cells are suitable. Further viral genomic promoter, control and / or signal sequences may be used, provided such control sequences are compatible with the host cell chosen.

[0058] Various promoters can be used in the chimeric adenoviral vectors described herein. In some embodiments, when the chimeric adenoviral vector expresses two or more nucleic acids, the promoters used to express the nucleic acids can be identical or different. For example, in some embodiments, a first promoter used to express an element (a) (e g., a norovirus VP1 protein codon-optimized sequence as described herein) and a second promoter used to express an element (b) (e.g., a TLR-3 agonist) can both be a CMV promoter, or the two promoters may be different, e.g., one promoter is a CMV promoter and the other promoter is an SV40 or beta-actin promoter. In other embodiments, when an element (c) is included, a third promoter can be identical or different from the first and / or second promoter. For example, the first promoter and the second promoter can both be a CMV promoter and the third promoter can be a beta-actin promoter (e.g., a human beta-actin promoter).

[0059] Expression cassettes to express polypeptides as described herein can contain additional regulatory elements such as a polyadenylation signal, e.g., bovine growth hormone polyadenylation signal, and other sequences to regulate expression, such as terminator sequences or RNA stability elements.

[0060] As noted above, the chimeric adenoviral vectors described herein (e.g., comprising a first promoter operably linked to a nucleic acid as described herein encoding the norovirus VP1 protein) can also include a nucleic acid comprising a second promoter operably linked to a nucleic acidencoding a toll-like receptor (TLR) agonist, which can serve as an effective adjuvant when administered in conjunction with viral vectors. For example, the chimeric adenoviral vectors of the disclosure can comprise an expression cassette comprising the following elements: (a) a first promoter operably linked to a nucleic acid encoding a norovirus VP1 protein; and (b) a second promoter operably linked to a nucleic acid encoding a toll-like receptor-3 (TLR-3) agonist. TLR agonists can be used to enhance the immune response to the norovirus VP1 protein. In some embodiments, TLR-3 agonists are used. In some embodiments, the TLR agonists described herein can be delivered simultaneously with the expression vector encoding an antigen of interest (e.g., a norovirus VP1 protein). In other embodiments, the TLR agonists can be delivered separately (i.e., temporally or spatially) from the expression vector encoding an antigen of interest (e.g., a norovirus VP1 protein). For example, the expression vector can be administered via a non-parenteral route (e.g., orally, intranasally, or mucosally), while the TLR agonist can be delivered by a parenteral route (e.g., intramuscularly, intraperitoneally, or subcutaneously),

[0061] In particular embodiments, a TLR-3 agonist is used to stimulate immune recognition of an antigen of interest, TLR-3 agonists include, for example, short hairpin RNA, vitally derived RNA, short segments of RNA that can form double-strands or short hairpin RNA, and short interfering RNA (siRNA). In one embodiment of the disclosure, the TLR-3 agonist is virally derived dsRNA, such as for example, a dsRNA derived from a Smdbis virus or dsRNA viral intermediates (Alexopoulou el al, Nature 413:732-8 (2001)). In some embodiments, the TLR-3 agonist is a short hairpin RNA. Short hairpin RNA sequences typically comprise two complementary sequences joined by a linker sequence. The particular linker sequence is not a critical aspect of the disclosure. Any appropriate linker sequence can be used so long as it does not interfere with the binding of the two complementary sequences to form a dsRN A.

[0062] In some embodiments, the TLR-3 agonist can comprise a sequence having at least 85%, 90%, 95%, 97%, 99%, or 100% (e.g., 85%, 87%, 89%, 91%, 93%, 95%, 97%, 99%, or 100%) identity to a sequence set forth in SEQ ID NOS: 12-20. In particular embodiments, the TLR-3 agonists comprises the sequence of SEQ ID NO:20. In certain embodiments, dsRNA that is a TLR-3 agonist does not encode a particular polypeptide, but produces a pro-inflammatory cytokine (e.g. IL-6, IL-8, TNF-alpha, IFN-alpha, IFN-beta) when contacted with a responder cell (e.g., a dendritic cell, a peripheral blood mononuclear cell, or a macrophage) in vitro or in-vivo.

[0063] In particular embodiments, the TLR agonist (e.g., TLR-3 agonist) described herein can be delivered simultaneously within the same the expression vector that encodes the norovirus VP1 protein. In other embodiments, the TLR agonist (e.g., TLR-3 agonist) can be delivered separately (z.e., temporally or spatially) from the expression vector that encodes the norovirus VP1 protein. In some cases when the TLR-3 agonist is delivered separately from the expression vector, the nucleic acid encoding the TLR-3 agonist (e.g, an expressed dsRNA) and the chimeric adenoviral vector comprising a nucleic acid encoding the norovirus VP1 protein can be administered in the same formulation. In other cases, the nucleic acid encoding the TLR-3 agonist and the chimeric adenoviral vector comprising a nucleic acid encoding the norovirus VP1 protein can be administered in different formulations. When the nucleic acid encoding the TLR-3 agonist and the adenoviral vector comprising a nucleic acid encoding the norovirus VP1 protein are administered in different formulations, their administration may be simultaneous or sequential. For example, the nucleic acid encoding the TLR-3 agonist may be administered first, followed by the chimeric adenoviral vector (e.g, 1, 2, 4, 8, 12, 16, 20, or 24 hours, 2, 4, 6, 8, or 10 days later). Alternatively, the adenoviral vector may be administered first, followed by the nucleic acid encoding the TLR-3 agonist (e.g., 1, 2, 4, 8, 12, 16, 20, or 24 hours, 2, 4, 6, 8, or 10 days later). In some embodiment, the nucleic acid encoding the TLR-3 agonist and the nucleic acid encoding the norovirus VP1 protein are under the control of the same promoter. In other embodiments, the nucleic acid encoding the TLR-3 agonist and the nucleic acid encoding the norovirus VP1 protein are under the control of different promoters.

[0064] In some embodiments, in addition to (a) a promoter operably linked to a nucleic acid as described herein encoding the norovirus VP1 and (b) a second promoter operably linked to a nucleic acid encoding a toll-like receptor-3 (TLR-3) agonist, the chimeric adenoviral vectors of the disclosure can further comprise (c) a third promoter operably linked to a nucleic acid encoding a second norovirus protein. In some embodiments, the order of the elements in the expression cassette from the N-terminus to the C -terminus is: element (a), element (c), and element (b); or element (c), element (a), and element (b).PHARMACEUTICAL COMPOSITIONS AND ROUTES OF ADMINISTRATION

[0065] An immunogenic pharmaceutical composition can contain one or more chimeric adenoviral vectors described herein and a pharmaceutically acceptable carrier. Suitable carriersinclude, for example, water, saline, alcohol, a fat, a wax, a buffer, a solid carrier, such as mannitol, lactose, starch, magnesium stearate, sodium saccharine, talcum, cellulose, glucose, sucrose, and magnesium carbonate, or biodegradable microspheres (e.g., polylactate polyglycolate). Suitable biodegradable microspheres are disclosed, for example, in US Patent Nos. 4,897,268; 5,075,109; 5,928,647; 5,811,128; 5,820,883. The immunogenic polypeptide and / or carrier expression vector can be encapsulated within the biodegradable microsphere or associated with the surface of the microsphere.

[0066] The ingredients in an immunogenic pharmaceutical composition are closely related to factors such as, but are not limited to, the route of administration of the immunogenic pharmaceutical composition, the timeline and / or duration of drug release, and the targeted delivery site. In some embodiments, a delayed release coating or an additional coating of the formulation can contain other film-forming polymers being non-sensitive to luminal conditions for technical reasons or chronographic control of the drug release. Materials to be used for such purpose includes but are not limited to; sugar, polyethylene glycol, polyvinylpyrrolidone, polyvinyl alcohol, polyvinyl acetate, hydroxypropyl cellulose, methylcellulose, ethylcellulose, hydroxypropyl methylcellulose, carboxymethylcellulose sodium and others, used alone or in mixtures.

[0067] Additives such as dispersants, colorants, pigments, additional polymers, e.g., poly(ethyl acrylate, methylmethacrylate), anti-tacking and anti-foaming agents can be included into a coating layer. Other compounds may be added to increase film thickness and to decrease diffusion of acidic gastric juices into the core material. The coating layers can also contain pharmaceutically acceptable plasticizers to obtain desired mechanical properties. Such plasticizers are for instance, but not restricted to, triacetin, citric acid esters, phthalic acid esters, dibutyl sebacate, cetyl alcohol, polyethylene glycols, glycerol monoesters, polysorbates or other plasticizers and mixtures thereof. The amount of plasticizer can be optimized for each formula, and in relation to the selected polymer(s), selected plasticizer(s) and the applied amount of said polymer(s).

[0068] Such immunogenic pharmaceutical compositions can also comprise non-immunogenic buffers (e.g., neutral buffered saline or phosphate buffered saline), carbohydrates (e.g., glucose, mannose, sucrose or dextrans), mannitol, proteins, polypeptides or amino acids such as glycine, antioxidants, bacteriostats, chelating agents such as EDTA or glutathione, adjuvants (e.g., aluminum hydroxide), suspending agents, thickening agents and / or preservatives. Alternatively,compositions of the present disclosure may be formulated as a lyophilate. Compounds may also be encapsulated within liposomes using well known technology.

[0069] Further, pharmaceutical compositions can be prepared to protect against stomach degradation such that the administered immunogenic biological agent reach the desired location. Methods for microencapsulation of DNA and drugs for oral delivery' are described, e.g., in US2004043952. For the oral environment, several of these are available including the Eudragit and the TimeClock release systems as well as other methods specifically designed for adenovirus (Lubeck el al., Proc Natl Acad Sci USA, 86(17), 6763-6767 (1989); Chourasia and Jain, J Pharm Pharm Sci, 6(1), 33-66 (2003)). In some embodiments, the Eudragit system can be used to deliver the chimeric adenoviral vector to the lower small intestine,

[0070] In particular embodiments, the immunogenic composition is in the form of a tablet or capsule, e.g., in the form of a compressed tablet covered by enteric coating. In some embodiments, the immunogenic composition is encapsulated in a polymeric capsule comprising gelatin, hydroxypropylmethylcellulose, starch, or pulhilan. In some embodiments, the immunogenic composition is in the form of microparticles less than 2 mm in diameter, e.g., each microparticle covered with enteric coating as described herein. In particular embodiments, the immunogenic composition in the form of a tablet, a capsule, or a microparticle can be orally administered. In some embodiments, site-specific delivery can be achieved via tablets or capsules that release upon an externally generated signal. Early models released for a high-frequency (HF) signal, as disclosed in Digenis etal. (1998) Pharm. Sci. Tech. Today 1: 160. The original HF capsule concept has since been updated and the result marketed as InteliSite®. The updated capsule is a radio¬ frequency activated, non-disintegrating delivery system. Radiolabeling of the capsule permits the determination of the capsule location within a specific region of the GI tract via gamma scintigraphy. When the capsule reaches the desired location in the GI tract, external activation opens a series of windows to the capsule drug reservoir.

[0071] In some embodiments, the immunogenic composition can be enclosed in a radio¬ controlled capsule, so that the capsule is tracked and signaled once it reaches the delivery site. In some embodiments, the capsule is signaled at a given time after administration that corresponds to when the capsule is expected to arrive at the delivery site, with or without detecting.

[0072] The compositions described herein may be administered as part of a sustained release formulation ( / .<?., a formulation such as a capsule or sponge that effects a slow release of compound following administration). Such formulations may generally be prepared using well known technology (see, e.g., Coombes et al. (1996) Vaccine 14:1429-1438). Sustained-release formulations may contain a polypeptide, polynucleotide or antibody dispersed in a carrier matrix and / or contained within a reservoir surrounded by a rate controlling membrane.

[0073] Carriers for use within such formulations are biocompatible and may also be biodegradable; preferably the formu lation provides a relatively constant level of active component release. Such carriers include microparticles of poly(lactide-co-glycolide), as well as polyacrylate, latex, starch, cellulose and dextran. Other delayed-release carriers include supramol ecul ar biovectors, which comprise a non-liquid hydrophilic core e.g., a cross-linked polysaccharide or oligosaccharide) and, optionally, an external layer comprising an amphiphilic compound (see, e.g., WO 94 / 20078; WO 94 / 23701; and WO 96 / 06638). The amount of active compound contained within a sustained release formulation depends upon the site of implantation, the rate and expected duration of release and the nature of the condition to be treated or prevented,

[0074] In some embodiments, the immunogenic compositions are presented in unit-dose or multi-dose containers, such as sealed ampoules or vials. Such containers are preferably hermetically sealed to preserve sterility of the formulation until use. In general, formulations can be stored as suspensions, solutions, or emulsions in oily or aqueous vehicles. Alternatively, an immunogenic composition may be stored in a freeze-dried condition requiring only the addition of a sterile liquid carrier immediately prior to use.

[0075] In some embodiments of targeted delivery, enteric coatings are used to shield substances from the low pH environment of the stomach and delay release of the enclosed substance until it reaches a desired target later in the digestive tract. Enteric coatings are known, and commercially available. Examples include pH-sensitive polymers, bio-degradable polymers, hydrogels, time¬ release systems, and osmotic delivery systems (see, e.g., Chourasia & Jam (2003) J. Pharm. Pharmaceutical Sci. 6:33).

[0076] In some embodiments, the targeted delivery site is the ileum. The pH of the gastrointestinal tract (GIT) progresses from very acidic in the stomach (pH ~2), to more neutral in the ileum (pH ~ 5.8-7.0). pH sensitive coatings can be used that dissolve m the ileum or just beforethe ileum. Examples include Eudragit® L and S polymers (threshold pH’s ranging from 5.5-7.0); polyvinyl acetate phthalate (pH 5.0), hydroxypropyl methylcellulose phthalate 50 and 55 (pH 5.2 and 5.4, respectively), and cellulose acetate phthalate (pH 5.0). Thakral etal. (2013) Expert Opin. Drug Deliv. 10: 131 review Euragit® formulations for ileal delivery, in particular, combinations of L and S that ensure delivery at pH<7.0. Crotts et al. (2001) Eur. J Pharm. Biol. 51:71 describe Eudragit® formulations with appropriate disintegration properties. Vijay et al. (2010) J. Mater. Sci. Mater. Med. 21:2583 review acrylic acid (AA)-methyl methacrylate (MMA) based copolymers for ileal delivery at pH 6.8,

[0077] For ileal delivery, the polymer coating typically dissolves at about pH 6.8 and allows complete release within about 40 min (see, e.g, Huyghebaert etal. (2005) Int. J. Pharm. 298:26). To accomplish this, a therapeutic substance can be covered in layers of different coatings, e.g., so that the outermost layer protects the substance through low pH conditions and is dissolved when the tablet leaves the stomach, and at least one inner layer that dissolves as the tablet passes into increasing pH. Examples of layered coatings for delivery to the distal ileum are described, e.g., in WO 2015 / 127278, WO 2016 / 200951, and WO 2013 / 148258.

[0078] Biodegradable polymers (e.g., pectin, azo polymers) typically rely on the enzymatic activity of microflora living in the GIT. The ileum harbors larger numbers of bacteria than earlier stages, including lactobacilli and enterobacteria.

[0079] Osmotic-control led Release Oral delivery Systems (OROS®; Alza) is an example of an osmotic system that degrades over time in aqueous conditions. Such materials can be manipulated with other coatings, or in varying thicknesses, to deliver specifically to the ileum (see, e.g., Conley et al. (2006) Curr. Med. Res. Opin. 22: 1879).

[0080] Combination polymers for delivery to the ileum are reported in W02000062820. Examples include Eudragit® LI 00-55 (25 mg / capsule) with triethyl citrate (2.4 mg / capsule), and Povidone K-25 (20 mg / tablet) followed by Eudragit® FS30D (30 mg / tablet). pH sensitive polymers can be applied to effect delivery to the ileum, as described above and, e.g., methacrylic acid copolymers (e.g., polyimetbacylic acid-co-methyl methacrylate) 1:1), cellulose acetate phthalate, hydroxypropyl methylcellulose phthalate, hydroxypropyl methylcellulose acetate succinate, polyvinyl acetate phthalate, cellulose acetate trimellitate, carboxymethyl ethyl¬ cellulose, shellac or other suitable polymer(s). The coating layer can also be composed of film-forming polymers being sensitive to other luminal components than pH, such as bacterial degradation or a component that has such a sensitivity when it is mixed with another film-forming polymer. Examples of such components providing delayed release to the ileum are polymers comprising azo bond(s), polysaccharides such as pectin and its salts, galactomannans, amylose and chondroitin, disulphide polymers and glycosides.

[0081] Components with varying pH, water, and enzymatic sensitivities can be used in combination to target a therapeutic composition to the ileum. The thickness of the coating can also be used to control release. The components can also be used to form a matrix, in which the therapeutic composition is embedded. See generally, Frontiers in Drug Design & Discovery (Bentham Science Pub, 2009) vol. 4.Adjuvant

[0082] In some embodiments of the present disclosure, in addition to the TLR agonist (e.g., TLR-3 agonist) encoded in the chimeric adenoviral vector, the compositions can further comprise additional adjuvants. Suitable adjuvants include, for example, the lipids and non-lipid compounds, cholera toxin (CT), CT subunit B, CT derivative CTK63, E. coli heat labile enterotoxin (LT), LT derivative LTK63, Al(OH)s, and polyionic organic acids as described in e.g., WO 04 / 020592, Anderson and Crowle, Infect. Immun. 31 (1):413-418 (1981), Roterman et al., J. Physiol. Pharmacol., 44(3):213-32 (1993), Arora and Crowle, J. Reticuloendothel. 24(3):271-86 (1978), and Crowle and May, Infect. Immun. 38(3):932-7 (1982)). Suitable polyionic organic acids include for example, 6,6’-[3,3’-demithyl[l,r-biphenyl]-4,4’-diyl]bis(azo)bis[4-amino-5-hydroxy-l,3- naphthalene-disulfomc acid] (Evans Blue) and 3,3’-[l,rbiphenyl]-4,4’-diylbis(azo)bis[4-amino-1 -naphthal enesulfonic acid] (Congo Red). It will be appreciated by those of skill in the art that the polyionic organic acids may be used for any genetic vaccination method in conjunction with any type of administration.

[0083] Other suitable adjuvants include topical immunomodulators such as, members of the imidazoquinolme family such as, for example, imiquimod and resiquimod (see, e.g., Hengge et al., Lancet Infect. Dis. 1 (3): 189-98 (2001).

[0084] Additional suitable adjuvants are commercially available as, for example, additional alum-based adjuvants (e.g., / Xlhydrogel, Rehydragel, aluminum phosphate, / Xlgammulin); oilbased adjuvants (Freund’s Incomplete Adjuvant and Complete Adjuvant (Difco Laboratories, Detroit, Mich.), Specol, RIBI, TiterMax, Montanide ISA50 or Seppic MONTANIDE ISA 720); nonionic block copolymer-based adjuvants, cytokines (e.g, GM-CSF or Flat3- ligand); Merck Adjuvant 65 (Merck and Company, Inc., Rahway, N. J.); AS-2 (SmithKline Beecham, Philadelphia, Pa.); salts of calcium, iron or zinc; an insoluble suspension of acylated tyrosine; acylated sugars; cationically or anionically derivatized polysaccharides; polyphosphazenes; biodegradable microspheres; monophosphoryl lipid A and Quil A. Cytokines, such as GM-CSF or interleukin-2, -7, or -12, are also suitable adjuvants. Hemocyanins (e.g., keyhole limpet hemocyanin) and hemoerythrins may also be used in the disclosure. Polysaccharide adjuvants such as, for example, chitin, chitosan, and deacetylated chitin are also suitable as adjuvants. Other suitable adjuvants include muramyl dipeptide (MDP, N acetylmuramyl I, alanyl D isoglutamme) bacterial peptidoglycans and their derivatives (e.g., threonyl-MDP, and MTPPE). BCG and BCG cell wall skeleton (CWS) may al o be used as adjuvants in the disclosure, with or without trehalose dimycolate. Trehalose dimycolate may be used itself (see, e.g., U. S. Pat. No. 4,579,945). Detoxified endotoxins are also useful as adjuvants alone or in combination with other adjuvants (see, e.g., U. S. Pat. Nos. 4,866,034; 4,435,386; 4,505,899; 4,436,727; 4,436,728; 4,505,900; and 4,520,019. The saponins QS21, QS17, QS7 are also useful as adjuvants (see, e.g., U. S. Pat. No.5,057,540; EP 0362279; WO 96 / 33739; and WO 96 / 11711). Other suitable adjuvants include Montanide ISA 720 (Seppic, France), SAF (Chiron, Calif., United States), ISCOMS (CSL), MF-59 (Chiron), the SBAS senes of adjuvants (e.g., SBAS-2, SBAS-4 or SBAS-6 or variants thereof, available from SmithKline Beecham, Rixensart, Belgium), Detox (Corixa, Hamilton, Mont.), and RC-529 (Corixa, Hamilton, Mont.).

[0085] Within the pharmaceutical compositions provided herein, the adjuvant composition can be designed to induce, e.g., an immune response predominantly of the Thl or Th2 type. High levels of Thl-type cytokines (e.g., IFN-gamma, TNF-alpha, IL-2 and IL-12) tend to favor the induction of cell mediated immune responses to an administered antigen. In contrast, high levels of Th2-type cytokines (e.g., IL-4, IL-5, IL-6 and IL-10) tend to favor the induction of humoral immune responses. Following oral delivery of a composition comprising an immunogenic polypeptide as provided herein, an immune response that includes Thl - and Th2-type responses will typically be elicited.

[0086] A composition comprising the chimeric adenoviral vector can be administered by any non-parenteral route (e.g., orally, intranasally, or mucosally via, for example, the vagina, lungs, salivary glands, nasal cavities, small intestine, colon, rectum, tonsils, or Peyer’s patches). The composition may be administered alone or with an adjuvant as described above. In particular embodiments, the immunogenic composition is administered orally in the form of a tablet or capsule. In further embodiments, the immunogenic composition is administered orally for targeted delivery in the ileum in the form of a tablet or capsule.METHODS

[0087] One aspect of the present disclosure involves using the immunogenic compositions described herein to elicit an antigen specific immune response towards a norovirus VP1 protein in a subject. Thus, provided herein is a method for eliciting an immune response towards a Norovirus VP1 protein in a subject comprising administering to the subject an immunogenically effective amount of one or more nucleic acids or vectors described herein. In some embodiments, the method comprises administering to the subject a single nucleic acid or vector comprising one or more norovirus VP1 antigens. For example, in some embodiments, the method may comprise administering to the subject a single nucleic acid or vector comprising a codon-altered coding sequence at least 85%, 90%, 95%, 98%, 99% or 100% identical to SEQ ID NO:3 or SEQ ID NO: 5, wherein the coding sequence encodes a Norwalk GI. l VP1 norovirus protein comprising SEQ ID NO: 9. In some embodiments, the method may comprise administering to the subject a single nucleic acid or vector comprising a codon-altered coding sequence at least 85%, 90%, 95%, 98%, 99% or 100% identical to SEQ ID NO:4 or SEQ ID NO:6, wherein the coding sequence encodes a Sydney GII.4 VP1 norovirus protein comprising SEQ ID NO: 10. In some embodiments, the method may comprise administering to the subject a single nucleic acid or vector comprising a codon-altered coding sequence at least 85%, 90%, 95%, 98%, 99% or 100% identical to SEQ ID NO:7 or SEQ ID NO: 8, wherein the coding sequence encodes a GII.17 VP1 norovirus protein comprising SEQ ID NO: 11. In some embodiments, the method may comprise administering to the subject two or more (e.g., 2, 3, or 4) single nucleic acids or vectors described herein in a sequential manner such that administration of one nucleic acid or vector is followed by administration or another nucleic acid or vector. In some embodiments, the single nucleic acids or vectors described herein are formulated as a tablet or capsule for oral deliveryand the method comprises administering to the subject two or more (e.g., 2, 3, or 4) tablets or capsules, each comprising a single nucleic acid or vector described herein.

[0088] In some embodiments, the method may comprise administering to the subject a tablet or capsule comprising a nucleic acid or vector comprising a codon-altered coding sequence at least 85%, 90%, 95%, 98%, 99% or 100% identical to SEQ ID NO:3 or SEQ ID NO:5, wherein the coding sequence encodes a Norwalk GI.l VPI norovirus protein comprising SEQ ID NO: 9, administering to the subject a tablet or capsule comprising a nucleic acid or vector comprising a codon-altered coding sequence at least 85%, 90%, 95%, 98%, 99% or 100% identical to SEQ ID NO:4 or SEQ ID NO:6, wherein the coding sequence encodes a Sydney GIL 4 VP1 norovirus protein comprising SEQ ID NO: 10, and administering to the subject a tablet or capsule comprising a nucleic acid or vector comprising a codon-altered coding sequence at least 85%, 90%, 95%, 98%, 99% or 100% identical to SEQ ID NO: 7 or SEQ ID NO: 8, wherein the coding sequence encodes a GII.17 VPI norovirus protein comprising SEQ ID NO: 11.

[0089] In some embodiments, the method may comprise administering to the subject a composition comprising two or more (e.g,, 2, 3, or 4) nucleic acids or vectors together as part of the same composition (e.g., tablet or capsule). For example, the method may comprise administering to the subject a bivalent or trivalent oral vaccine. For example, in some embodiments, the method may comprise administering to the subject a composition comprising a nucleic acid or vector comprising a codon-altered coding sequence at least 85%, 90%, 95%, 98%, 99% or 100% identical to SEQ ID NO: 3 or SEQ ID NO: 5, wherein the coding sequence encodes a Norwalk GI.l VPI norovirus protein comprising SEQ ID NOV and a nucleic acid or vector comprising a codon-altered coding sequence at least 85%, 90%, 95%, 98%, 99% or 100% identical to SEQ ID NO:4 or SEQ ID NO:6, wherein the coding sequence encodes a Sydney GII.4 VPI norovirus protein comprising SEQ ID NO: 10. / Xs another example, in some embodiments, the method may comprise administering to the subject a composition comprising a nucleic acid or vector comprising a codon-altered coding sequence at least 85%, 90%, 95%, 98%, 99% or 100% identical to SEQ ID NO: 3 or SEQ ID NO: 5, wherein the coding sequence encodes a Norwalk GI.l VPI norovirus protein comprising SEQ ID NOV, a nucleic acid or vector comprising a codon-altered coding sequence at least 85%, 90%, 95%, 98%, 99% or 100% identical to SEQ ID NO: 4 or SEQ ID NO: 6, wherein the coding sequence encodes a SydneyGII.4 VP1 norovirus protein comprising SEQ ID NO: 10, and a nucleic acid or vector comprising a codon-altered coding sequence at least 85%, 90%, 95%, 98%, 99% or 100% identical to SEQ ID NO:4 or SEQ ID NO:6, wherein the coding sequence encodes a GIL 17 VP1 norovirus protein comprising SEQ ID NO: 11.

[0090] In some embodiments, the method comprises administering the nucleic acids or vectors described herein to the subject orally, intranasally, or mucosally. In some embodiments, the method comprises administering nucleic acids or vectors described herein to the subject orally by swallowing a tablet or capsule.

[0091] In some embodiments, the immune response is elicited in an alveolar cell, an absorptive enterocyte, a ciliated cell, a goblet cell, a club cell, and / or an airway basal cell of the subject. As used herein, a “subject” refers to any warm-blooded animal, such as, for example, a rodent, a feline, a canine, or a primate, preferably a human. The immunogenic compositions can be used before the subject developed norovirus to prevent disease. The disease can be diagnosed using criteria generally accepted in the art. For example, viral infection can be diagnosed by the measurement of viral titer in a biological sample from the subject. The immune response can be induced in a subject prior to infection by norovirus (e.g,, to prevent a future information or reduce the resulting symptoms if infection later occurs) or during an active infection by norovirus.

[0092] Frequency of administration of the immunogenic composition described herein, as well as dosage, will vary from individual to individual, and may be readily established using standard techniques. In some embodiments, between 1 and 10 (e.g., between 2 and 10, between 3 and 10, between 4 and 10, between 5 and 10, between 6 and 10, between 7 and 10, between 8 and 10, between 9 and 10, between 1 and 9, between I and 8, between 1 and 7, between 1 and 6, between 1 and 5, between 1 and 4, between 1 and 3, or between 1 and 2) doses may be administered over a 52 week period. In some embodiments, 2 or 3 doses are administered at intervals of 1 month; or for example, 2-3 doses are administered every 2-3 months. It is possible that the intervals will be once a year for certain therapies. Booster vaccinations may be given periodically thereafter.

[0093] A suitable dose is an amount of a compound for example that, when administered as described above, is capable of promoting an anti-viral immune response, and is at least 10-50% above the basal ( / .e., untreated) level. Such response can be monitored by measuring the anti-viralantibodies in a patient or by vaccine-dependent generation of cytolytic T cells capable of killing, e.g., the patient’s virus-infected cells in vitro. Immunogenic responses can also be measured by detecting immunocomplexes formed between the immunogenic polypeptides and antibodies in body fluid which are specific for the immunogenic polypeptides. Samples of body fluid taken from an individual prior to and subsequent to initiation of therapy may be analyzed for the immunocomplexes. Briefly, the number of immunocomplexes detected in both samples can be compared. A substantial change in the number of immunocomplexes in the second sample (post¬ therapy initiation) relative to the first sample (pre-therapy) reflects successful therapy. Such vaccines should also be capable of causing an immune response that leads to prevention of norovirus-induced disease in vaccinated patients as compared to non-vaccinated patients.

[0094] Exemplary dosages can be measured in infectious units (I. U.). A replication-deficient recombinant Ad5 vector can be titered and quantified using LU. units. This is accomplished through performance of an IU assay in the adherent human embryonic kidney (HEK) 293 cell line, which is permissive for growth of replication-deficient Ad5. HEK293 cells are plated in a 24-well sterile tissue culture plate and allowed to adhere. The viral material is diluted in sequential 10-fold dilutions and infected into individual wells of plated HEK293 cells in an appropriate number of replicates, usually in duplicate or triplicate. Infection is allowed to proceed via incubation for ~40-42 hours at 37C, 5% CO2. Cells are then fixed with methanol to allow permeability, washed, and blocked with a buffer solution containing bovine serum albumin (BSA). Cells are then incubated with a rabbit-derived primary antibody against the Ad5 hexon surface protein, washed, and probed again with an HRP-conjugated anti-rabbit secondary antibody. Infected cells are then stained via incubation with 3,3'-diaminobenzidine tetrahydrochloride (DAB) and hydrogen peroxide. Infected cells are visualized using phase-contrast microscopy and a dilution is chosen that exhibits discreet individual infection events - these are visible as darkly stained cells that are highly visible against the semi-transparent monolayer of uninfected cells. Total infected cells are counted per field-of-vision in at least ten fields-of- vision of the appropriate dilution. Viral titer can be calculated using the average number of these counts m conjunction with the total number of fields-of- vision for the objective lens / eyepiece magnification used and multiplying by the dilution factor used in the counts.

[0095] In some embodiments, the vaccines administered can have a dosage of lO'-l 011, e.g., 108- 1011, 109-10n, 5xlO9-5xlO10LU. Suitable dose sizes will vary with the size of the patient, but will typically range from about 0.01 ml to about 10 ml for an injected vaccine, more typically from about 0.025 to about 7.5 ml, most typically from about 0.05 to about 5 ml. For a tablet or capsule final product, the size would be between 10 mg to 1000 mg, most typically between 100-400 mg. Those of skill in the art will appreciate that the dose size may be adjusted based on the particular patient or the particular disease or disorder being treated.EXAMPLESExample 1

[0096] This example shows that codon optimized sequences SEQ ID NO: 5 (ED 150) and SEQ ID NO:3 (WS23) improve expression of the respective mRNA encoding the Norwalk Gl.l VP1 protein (SEQ ID NO:9) from norovirus compared to a previously-developed VPl-coding sequence (CS186; SEQ ID NO: 1). SEQ ID NO:5 has 79.7% sequence identity with SEQ ID NO: 1. SEQ ID NO: 3 has 77.9% sequence identity’ with SEQ ID NO: 1. SEQ ID NO: 3 and SEQ ID NO: 5 have 84.6% sequence identity.

[0097] Flow cytometry analysis of transduced HIEC-6 cells stained with MAB228P antibody specific for norovirus Gl.l VP1 was performed using SEQ ID NO:5 (ED150) and SEQ ID NO:3 (WS23) as well as SEQ ID NO: 1 (CS186). The full-length Adenovirus vector sequences are shown in SEQ ID NO:21 (CS186 Ad vector), SEQ ID NO: 25 (EDI 50 Ad vector) and SEQ ID NO:23 (WS23 Ad vector). A schematic drawing of these vectors is shown in FIG, 1 A. FIG. IB shows the relative VP1 protein expression from these vectors in HIEC-6 cells.Example 2

[0098] This example shows that codon optimized sequences SEQ ID NO:6 (EDI 53) and SEQ ID NO:4 (WS24) improve expression of the respective mRNA encoding the Sydney GIL 4 VP1 protein (SEQ ID NO: 10) from norovirus compared to a previously-developed VPl-coding sequence (EDU; SEQ ID NO:2). SEQ ID NO:6 has 78.9% sequence identity with SEQ ID NO: 2. SEQ ID NO:4 has 80.2% sequence identity with SEQ ID NO: 2, SEQ ID NO: 4 and SEQ ID NO:6 have 86,4% sequence identity.

[0099] Flow cytometry analysis of transduced HIEC-6 cells stained with MAB228P antibody specific for norovirus GII.4 VP1 was performed using SEQ ID NO:6 (EDI 53) and SEQ ID NO:4 (WS24) as well as a previously-developed VPl-coding sequence (EDI 1; SEQ ID NO:2). The full- length Adenovirus vector sequences are shown in SEQ ID NO:22 (EDI 1 Ad vector), SEQ ID NO: 26 (EDI 53 Ad vector) and SEQ ID NO:24 (WS24 Ad vector). A schematic drawing of these vectors is shown in FIG. 2 A. FIG. 2B shows the relative VP1 protein expression from these vectors in HIEC-6 cells.Example 3

[0100] This example shows new GI.l construct (EDI 50) elicited increased antibody production in mice compared to an older vector.

[0101] Balb / c mice were treated with different dilutions of adenoviral constructs CS186 and EDI 50 expressing norovirus GI.l VP1. Animals were dosed on Day 0 and then boosted on Day 29. Mice sera were collected on Days 14, 28, and 42. Serum IgG specific for GI. l VP1 was measured using MSD (Mesoscale) assay, with level of binding expressed in RLU units. EDI 50 induced higher level of VP1 -specific IgG at lower concentrations (Ie5-le6) than CS186, thus demonstrating greater potency. See table below and FIG. 3.ED150 improvement over Fold rise over PBS CS186CS186 ED150PBS 1 1 1.0le4 12.6 27.2 2.2le5 7.7 1069.8 138.4le6 688.6 2101.5 3.1le7 2009.5 2152.9 1.1Example 4

[0102] This example shows a new GII.4 construct (EDI 53) elicited increased antibody production in mice compared to an older vector.

[0103] Balb / c mice were treated with different dilutions of adenoviral constructs ED 11 and EDI 53 expressing norovirus GIL 4 VPl. Animals were dosed on Day 0 and sera were collected on Days 14 and 28. Serum IgG specific for GII.4 VPl was measured using MSD (Mesoscale) assay, with level of binding expressed in RLU units. EDI 53 induced higher level of VPl -specific IgG at a lower concentration (le6) than EDI 1, thus demonstrating greater potency and immunogenicity. See table below and FIG. 4.ED 153 improvement over Fold rise over PBS historic EDI 1EDll ED153PBS 1.0 1 1.0le4 1.4 1.4 1.0le5 1,3 2.3 1.8le6 1.5 127.9 83.5le7 263.1 809.0 3.1Example 5

[0104] Immunogenicity assessment of legacy (CS186 and EDl l) and novel (EDI 50 and EDI 53) norovirus vaccines was conducted in hamsters. Animals received norovirus GI.1 vaccines, CS186 or EDI 50, and norovirus GII.4 vaccines, EDll or EDI 53, via oral gavage. The vaccination and sample collection schedule is shown in FIG. 5. Briefly, each group consisted of eight animals, which were vaccinated on Days 0 and 28 with 1x109IU of the respective adenoviral vector. Blood samples and oral swabs were collected on days -1, 27, and 42, while fecal samples were obtained on days -1 and 42. Antibody responses in these samples were quantified using MesoScaleDiscovery (MSD) assays to determine binding to the corresponding GI.l or GII.4 VP1 virus-like particles.

[0105] Hamsters given the EDI 50 norovirus GI.1 adenoviral vector showed greater increases in serum IgG (FIG 6 A) and IgA (FIG. 6B) than those with the CS186 norovirus GI. l adenoviral vector on days 27 and 42. MSD signal in FIGs. 6A and 6B is reported as fold increase over day - 1. Likewise, Hamsters given the EDI 53 norovirus GII.4 adenoviral vector showed greater increases in serum IgG (FIG. 7A) and IgA (FIG. 7B) than those with the EDU norovirus GII.4 adenoviral vector on days 27 and 42. MSD signal in FIGs. 7A and 7B is reported as fold increase over day -1

[0106] Fecal sample assessment showed hamsters vaccinated with the EDI 50 norovirus GI.l adenoviral vector showed higher fecal anti-GI. l IgA than those with the CS186 norovirus GI. l adenoviral vector on day 42 (FIG. 8A). Similarly, hamsters vaccinated w’ith the EDI 53 norovirus GII.4 adenoviral vector show'ed higher fecal anti-GII.4 IgA than those with the EDU norovirus GII 4 adenoviral vector on day 42 (FIG. 8B).

[0107] Salivary assessment showed hamsters vaccinated with the EDI 50 norovirus GI.l adenoviral vector showed higher salivary anti-GI.1 IgA than those with the CS186 norovirus GI.1 adenoviral vector on days 28 and 42 (FIG. 9A), Similarly, hamsters vaccinated with the EDI 53 norovirus GII.4 adenoviral vector showed higher salivary anti-GII.4 IgA than those with the EDI 1 norovirus GII.4 adenoviral vector on days 28 and 42 (FIG, 9B). In FIGs, 11 A and 1 IB, MSD signal is expressed as fold rise in comparison to day -1 levels.Example 6

[0108] Immunogenicity results were obtained from a Phase 1, single-center, open-label dose escalation study assessing a novel oral bivalent norovirus GI.1 / GII.4 vaccines EDI 1 and ED153. Participants were healthy adults aged 18 to 80 years. A total of sixty participants were randomized into three groups of twenty individuals as described in the table below.Arm T reatment1 Bivalent high dose of the ED150 GI. I vaccine (1 *1011IU) plus ED153 GII.4 vaccine (IxlO11IU) (n::::20).2 Bivalent high dose of the CS186 GI.1 vaccine (1 * 1010IU) plus EDI 1 GII.4 vaccine(1 - 1010IU) (n=20).3 Bivalent high dose of the ED150 GI. I vaccine (1 *1011IU) plus ED153 GII.4 vaccine(IxlO11!!!) (n=20).

[0109] Serum samples were obtained from trial participants, and the functional antibodies targeting GI.l and GII.4 were quantified using the norovirus blocking antibody assay (NBAA), which evaluates the capacity of serum antibodies to inhibit interactions between norovirus virus¬ like particles and the histo-blood group antigen receptor. Additionally, levels of anti-GI.1 and anti-GII.4 IgA were determined in fecal specimens collected from the same participants.

[0110] At day 28 post treatment, novel EDI 50 and EDI 53 norovirus GI.1 vaccines at both dose levels produced higher anti-GI.1 NBAA titers (FIG. 10A) and greater fold increases (FIG. 10B) than previously-developed CS186 and ED 11 norovirus GI.l vaccines. Likewise, at day 28 post treatment, novel EDI 50 and EDI 53 norovirus GI.l vaccines at both dose levels produced higher anti-GII.4 NBAA titers (FIG. 11 A) and greater fold increases (FIG. 11B) than previously-developed CS186 and EDI 1 norovirus GII.4 vaccines.

[0111] High doses of the ED150 and ED153 norovirus vaccines induced greater levels of anti-GI.l (FIG. 12A) and anti-GII.4 (FIG. 12B) fecal IgA relative to the low dose ED150 and ED153 and high dose CS186 and ED 11 -receiving groups. This elevated fold increase persisted from day 28 through day 179 following treatment (FIGs. 12A and 12B).Example 7

[0112] Previously-developed (CS186 and ED11) and novel (ED 150 and EDI 53) norovirus adenoviral vectors were evaluated for expression of VP1 in differentiated human enteroid cultures. Human enteroids differentiated in transwells were transduced with the vectors at a multiplicity of infection (MOI) equal to 200. After 48 hours, the cells were fixed and permeabilized for immunohistochemical staining with anti-VPl antibody. Stained samples were imaged using a Biotek Cytation® 7 (Agilent, Santa Clara, CA) multimode reader, and VP1 protein expression was quantified using the Biotek Gen5® software (Agilent, Santa Clara, CA).10113] Cytation® 7 imaging showed VP1 protein expression in differentiated ileum enteroid cultures following transduction with ED 11 (FIG. 13 A) and EDI 53 (FIG. 13B) norovirus GII.4 adenoviral vectors. D API-normalized quantification compares GI.l VP1 expression in humanenteroids following transduction with CS186 versus ED150 vectors (FIG. 14A) and GIL 4 VP1 expression following transduction with ED11 and EDI 53 vectors (FIG. 14B).

[0114] The foregoing examples are provided by way of illustration only, and not by way of limitation. Those of skill in the art will readily recognize a variety of non-critical parameters that could be changed or modified to yield essentially the same or similar results.Exemplary Embodiments

[0115] Exemplary embodiments provided in accordance with the presently disclosed subject matter include, but are not limited to, the claims and the following embodiments:1. A nucleic acid comprising a codon-altered coding sequence at least 85%, 90%, 95%, 98%, 99% or 100% identical to SEQ ID NO:3 or SEQ ID NO:5, wherein the coding sequence encodes a Norwalk GI.1 VP1 norovirus protein comprising SEQ ID NO: 9.2. The nucleic acid of embodiment 1, comprising a first promoter operably linked to the coding sequence.3. The nucleic acid of embodiment 2, wherein the first promoter comprises the CMV promoter or the SV40 promoter.4. The nucleic acid of any one of embodiments 2 or 3, wherein the first promoter is inducible.5. The nucleic acid of embodiment 4, wherein the first promoter comprises a let operator.6. The nucleic acid of any one of embodiments 1-3, wherein the nucleic acid is a vector.7. The nucleic acid of embodiment 4, wherein the vector is a viral vector.8. The nucleic acid of embodiment 7, wherein the viral vector is an adenoviral vector.9. The nucleic acid of embodiment 8, wherein the adenoviral vector comprises a second promoter operably linked to a nucleic acid encoding a toll-like receptor-3 (TLR-3) agonist.10. The nucleic acid of embodiment 9, wherein the TLR-3 agonist is a dsRN A.11. The nucleic acid of embodiment 9, wherein the first promoter and the second promoter have different sequences.12. The nucleic acid of embodiment 11, wherein the first promoter and second promoter are independently selected from a CMV promoter and an SV40 promoter.13. The nucleic acid of embodiment 12, wherein the first promoter comprises a CMV promoter and the second promoter comprises an SV40 promoter.14. The nucleic acid of embodiment 13, wherein the CMV promoter comprises a Tet operator, rendering the CM\?promoter inducible.A nucleic acid comprising a codon-altered coding sequence at least 85%, 90%, 95%, 98%, 99% or 100% identical to SEQ ID NO: 4 or SEQ ID NO: 6, wherein the coding sequence encodes a Sydney GII.4 VP1 norovirus protein comprising SEQ ID NO: 10. The nucleic acid of embodiment 15, comprising a first promoter operably linked to the coding sequence.The nucleic acid of embodiment 16, wherein the first promoter comprises the CMV promoter or the S V40 promoter.The nucleic acid of any one of embodiments 16 or 17, wherein the first promoter is inducible.The nucleic acid of embodiment 18, wherein the first promoter comprises a Tet operator.The nucleic acid of any one of embodiments 15-17, wherein the nucleic acid is a vector.The nucleic acid of embodiment 18, wherein the vector is a viral vector.The nucleic acid of embodiment 21, wherein the viral vector is an adenoviral vector. The nucleic acid of embodiment 22, wherein the adenoviral vector comprises a second promoter operably linked to a nucleic acid encoding a toll-like receptor-3 (I'LR-3) agonist.The nucleic acid of embodiment 23, wherein the TLR-3 agonist is a dsRN / X.The nucleic acid of embodiment 23, wherein the first promoter and the second promoter have different sequences.The nucleic acid of embodiment 25, wherein the first promoter and second promoter are independently selected from a CMV promoter and an SV40 promoter.The nucleic acid of embodiment 26, wherein the first promoter comprises a CMV promoter and the second promoter comprises an SV40 promoter.The nucleic acid of embodiment 27, wherein the CMV promoter comprises a Tet operator, rendering the CMV promoter inducible.A nucleic acid comprising a codon-altered coding sequence at least 85%, 90%, 95%, 98%, 99% or 100% identical to SEQ ID NOV or SEQ ID NO: 8, wherein the coding sequence encodes a Gil 17 VP1 norovirus protein comprising SEQ ID NO: 11.The nucleic acid of embodiment 29, comprising a first promoter operably linked to the coding sequence.The nucleic acid of embodiment 30, wherein the first promoter comprises the CMV promoter or the S V40 promoter.The nucleic acid of any one of embodiments 30 or 21, wherein the first promoter is inducible.The nucleic acid of embodiment 32, wherein the first promoter comprises a Tet operator.The nucleic acid of any one of embodiments 29-31, wherein the nucleic acid is a vector.The nucleic acid of embodiment 32, wherein the vector is a viral vector.The nucleic acid of embodiment 35, wherein the viral vector is an adenoviral vector. The nucleic acid of embodiment 36, wherein the adenoviral vector comprises a second promoter operably linked to a nucleic acid encoding a toll -like receptor-3 (TLR-3) agonist.The nucleic acid of embodiment 37, wherein the TLR-3 agonist is a dsRNA.The nucleic acid of embodiment 37, wherein the first promoter and the second promoter have different sequences.The nucleic acid of embodiment 39, wherein the first promoter and second promoter are independently selected from a CMV promoter and an SV40 promoter.The nucleic acid of embodiment 40, wherein the first promoter comprises a CMV promoter and the second promoter comprises an SV40 promoter.The nucleic acid of embodiment 41, wherein the CMV promoter comprises a Tet operator, rendering the CMV promoter inducible.A method for eliciting an immune response towards a Norovirus VP1 protein in a subject, the method comprising administering to the subject an immunogenically effective amount of one or more nucleic acids of any one of claims 1-42 to a mammalian subject.The method of embodiment 43, wherein the administering is oral, mtranasal, or mucosal.The method of embodiment 44, wherein the administering is oral delivery by swallowing a tablet or capsule.The method of embodiment 43, wherein the method comprises administering to the mammalian subject an immunogenically effective amount of two nucleic acids of any¬ one of claims 1-42.The method of embodiment 43, wherein the method comprises administering to the mammalian subject an immunogenically effective amount of three nucleic acids of any one of claims 1-42.The method of any one of embodiments 43-45, wherein the immune response is elicited in an alveolar cell, an absorptive enterocyte, a ciliated cell, a goblet cell, a club cell, a dendritic cell, a macrophage, and / or an airway basal cell of the subject. The method of any one of embodiments 43-48 wherein the subject is a human.A pharmaceutical composition comprising one or more vectors of any one of embodiments 6-14 or 20-28 or 34-42.The pharmaceutical composition of embodiment 50, wherein the pharmaceutical composition is a tablet or a capsule.PATENT Attorney Docket No. 090402-1544030-002710PCSEQUENCESNorovirus VP1 Transgene Coding SequencesSEQ IE NO: 1> CS186 GI. 1 VP1 coding sequence ATGATGATGGCGAGTAAAGACGCTACATCCTCCGTGGATGGGGCCTCTGGAGCAGGTCAGCTGGTGCCGGAGGTGAA CGCATCAGATCCTCTTGCTATGGACCCAGTGGCAGGAZIGCAGTACTGCAGTCGCTACTGCTGGACAAGTAAATCCCA TCGATCCCTGGATCATCAATAACTTCGTGCAGGCCCCACAAGGCGAATTTACTATTTCCCCCAACAACACGCCTGGC GATGTGTTGTTCGATCTGTCTCTTGGCCCCCATCTGAACCCCTTTCTGTTGCATCTCTCCCAGATGTACAATGGCTG GGTGGGCAATATGCGCGTGCGCATTATGTTGGCCGGTAACGCGTTTACAGCTGGAAAAATAATCGTGAGCTGCATTC CTCCCGGCTTCGGTTCCCATAATCTGACAATAGCGCAGGCTACCCTGTTCCCTCACGTGATCGCGGATGTGAGAAOA CTTGATCCCATAGAGGTGCCTCTGGAAGACGTGAGAAATGTCTTGTTCCATAATAATGACCGGAATCAACAAACAAT GAGGCT GGT GT GC T GTT GT CACAC CT CT GCGGAC GGGC GGC GGAACAGGGGACT CATT T GT AGT GGCAGGAAGAG TGATGACCTGCCCTTCTCCCGACTTCAATTTCCTGTTTTTGGTTCCTCCCACAGTCGAGCAGAAGACTAGGCCATTT ACCCTGCCCAATCTCCCGCTTAGCTCACTGTCTAATTCAZIGAGCACCGCTGCCAATTTCTTCAATGGGCATTTCCCC GGACAATGTGCAGTCCGTTCAATTCCAGAACGGCAGGTGTACGCTGGATGGCAGACTTGTCGGCACTACACCGGTCA GCCTCTCACACGTTGCCAAAATTCGGGGTACTTCCAACGGCACGGTCATCAZICTTGACCGAGCTGGACGGGACCCCG TTCCACCCCTTTGAGGGCCCCGCTCCTATCGGGTTTCCCGATCTGGGAGGGTGTGATTGGCACATCAACATGACACA GTTTGGGCATAGCTCACAGACGCAGTACGACGTCGATACCACCCCTGACACATTCGTGCCGCATCTCGGCTCAATCC AGGCAAACGGCATAGGGAGTGGTATTTATGTCGGTGTCTTGAGTTGGATCTCTCCGCCCTCTCACCCTTCCGGTTCC CAAGTAGACCTCTGGAAGATCCCCAATTACGGCTCCTCTATCACCGAGGCCACCCACTTGGCCCCATCCGTCTATCC CCCAGGATTCGGGGAGGTACTCGTTTTCTTCATGAGTATGATGCCTGGTCCTGGCGCCTACAATCTGCCTTGCTTGT TGCCCCAGGAGTACATTAGCCACCTGGCCTCTGAACAGGCCCCCACCGTGGGAGAAGCCGCTTTGTTGCATTACGTC GACCCCGACACCGGTAGAAACCTGGGAGAGTTTAAIGCATATCCTGATGGGTTCCTTACCTGCGTGCCCAATGGCGC ATCATCTGGCCCCCAGCAGCTGCCGATCAATGGCGTTTTCGTCTTTGTGTCCTGGGTATCCCGCTTCTACCAGCTGA AGCCGGTTGGCACAGCCTCATCAGCACGCGGCAGACTGGGCCTCAGAAGATA?!SEQ IE NO: 2> EE11 GII. 4 VP1 codon-optimized coding sequence ATGAAGATGGCTAGCAGCGATGCCAATCCGAGTGATGGGTCCGCAGCCAATCTGGTCCCGGAGGTTAACAATGAAGT GATGGCTCTGGAACCTGTGGTGGGTGCTGCAATCGCCGCACCTGTTGCAGGGCAGCAGAACGTTATTGATCCCTGGA TCAGGAACAACTTCGTGCAAGCACCCGGCGGTGAATTCACCGTGAGCCCCAGGAACGCCCCAGGCGAAATTCTGTGG TCTGCCCCACTGGGGCCTGATCTGAACCCCTATCTGTCTCACCTGGCAAGAAi'GTATAACGGGTATGCCGGAGGGTT TGAGGTCCAGGTCATCCTGGCGGGAAACGCCTTTACTGCAGGCAAGGTGATATTTGCGGCCGTACCTCCCAATTTTC CAACCGAGGGACTTAGCCCATCCCAGGTGACA TGTTTCCTCACATCGTGGTCGATGTGCGCCAGCTTGAGCCAGTC CTGATTCCACTGCCAGACGTGAGAAATAACTTTTATCATTACAATCAATCAAACGACCCAACCATCAAACTGATCGC CATGCTGTACACTCCTCTTCGCGCCAACAACGCTGGTGACGATGTGTTTACAGTGTCTTGTCGGGTCCTCACTCGCC CCTCCCCAGATTTTGACTTTATTTTTCTCGTGCCGCCAACGGTTGAAAGTAGGACAAAGCCTTTCTCCGTACCAGTG CTCACTGTGGAGG G TG CC C GCCGGTTTCCGATCCCTCTGG G ACTGTTCACGGGGCCTTCT GTGCTTT CGTGGTTCAGCCACAAAACGGGAGGTGCACCACAGATGGCGTACTGCTTGGGACTACCCAGCTTAGCCCCGTGAATA TTTGTACCTTCCGGGGGGATGTGACACACATTACCGGCTCCAGGAACTATACCATGAATCTGGCCTCCCAAAATTGG AACGACTATGATCCCACCGAGGAGATCCCTGCCCCTCTGGGCACTCCTGACTTTGTTGGAAAGATACAGGGCGTCCT GACACAAA. CAACAAGAACCGATGGCTCTACCCGGGGGCATAAGGCAACCGTGTACACTGGGTCCGCTGACTTTGCGC CCAAACTGGGACGGGTCCAATTCGAGACTGACACAGACCGAGACTTCGAGGCGAATCAGAACACAAAGTTCACCCCT GTCGGTGTGATTCAGGACGGGGGCACCACTCATCGGAACGAGCCCCAaCAGTGGGTCTTGCCCTCCTACTCCGGGAG GAATACTCACAIlTGTTCACCTGGCCCCCGCCGTGGCCCCCACGTTCCCAGGTGAACAACTGCTGTTTTTTAGATCTA CTATGCC'rGGTTGT'T'CCGGCTATCCAAAlArGGACCTTGAT'T'GTCTGCTGCCACAGGAGTGGGTGCAGTATTTCTAC CAGGAAGCAGCCCCAGCCCAGTCAGATGTTGCCTTGCTTCGGTTCGTGAATCCTGATACCGGGAGGGTTCTCTTCGA ATGCAAGCTGCACAAATCTGGCTACGTGACGGTAGCGCATACTGGACAGCATGACCTCGTCATTCCCCCAAACGGAT ACTTTCGATTCGATAGCTGGGTAAZICCAGTTTTATACACTGGCACCTATGGGCAACGGGACCGGCAGGAGGCGGGCG GTGT ASEQ ID NO: 3> WS23 GI. 1 VP1 codon-optimized coding sequence ATGATGATGGCCTCAAAGGACGCCACAAGCTCTGTGGATGGCGCCTCTGGCGCCGGCCAGCTCGTGCCTGAGGTGAA CGCCAGCGACCCTCTGGCCATGGACCCCGTGGCCGGCTCCAGCACCGCCGTGGCCACCGCCGGCCA4GTGAA0CCCA TCGACCCCTGGATCATCAACAACTTCGTGCAGGCACCCCAGGGCGAGTTCACCATCAGCCCTAACAACACCCCTGGA GATGTGCTGTTCGACCTGTCTCTGGGACCTCACCTGAAOCCTTTCCTGCTGCACCTGTCTCAGATGTACAACGGCTG GGTGGGCAACATGCGTGTGAGAATCATGCTGGCTGGAAATGCCTTCACAGCTGGCAAGATCATCGTGAGCTGCATCC CTCCTGGCTTCGGCAGCCATAAICTGACCATTGCCCAGGCTACACTGTTCCCCCACGTGATCGCCGATGTGCGGACC CTGGATCCAATCGAGGTGCCCCTGGAAGATGTGCGGAACGTGCTGTTTCACAACAACGACAGAAACCAGCAGACCAT GAGACTGGTGTGCATGCTGTACACCCCACTCAGAA. CCGGCGGAGGAACCGGCGACAGCTTCGTGGTGGCTGGCAGAG TGATGACCTGTCCTAGCCCCGACTTCAACTTCCTGTTTCTGGTTCCTCCTACCGTGGAACAGAAGACCAGACCCTTT ACCCTGCCTAATCTGCCTCTGAGTTCTCTGAGCAACAGCAGAGCCCCCCTGCCTATTTCCAGCATGGGCATCTCCCC CGATDAGGTGCAGAGCGTGCAATTTCAGAACGGCAGGTGTACCCTCGACGGCAGACTGGTCGGAACAADCCCCGTGA GCCTGAGCCACGTGGCCAAGATCCGGGGCACATCCAACGGCACAGTTATCAATCTGACCGAGCTGGACGGCACCCCT TTCCACCCTTTCGAGGGCCCTGCCCCTATCGGCTTTCCTGACCTGGGGGGCTGCGACTGGCACATCAAOATGACCCA GTTCGGCCACAGCAGCCAGACACAATACGACGTGGACACCACCCCTGATACCTTCGTGCCACATCTGGGCAGCATCC AGGCCDACGGGATCGGCAGCGGCAArTACGTGGGAGTGCTGAGCTGGATCAGCCCTCCAAGCCACCCCAGCGGAAGC CAGGTGGACCTGTGGAAGATTCCTAACTACGGCTCTAGCATCACCGAGGCCACACACCTGGCCCCTAGCGTGTACCC TCCAGGCTTCGGCGAAGTCCTGGTCTTCTTCATGAGCAAAATGCCCGGCCCCGGAGCCTACAA CTGCCCTGCCTGC TACCTCAGGAGTACATCTCTCACCTGGCCTCCGAGCAAGCTCCTACAGTGGGAGAAGCCGCCCTGCTGCACTACGTG GACCCTGACACAGGCCGGAACCTGGGCGAATTCAADGCCTATCCTGATGGATTTCTGACATGCGTGCCTAAOGGCGC TAGCTCCGGCCCTCAGCAGCTGCCTATCAACGGCGTGTTCGTGTTCGTCTCCTGGGTCAGCAGATTCTACCAGCTTA AACCTGTGGGCACCGCTTCTAGCGCCAGAGGCCGCCTCGGCCTGCGGAGATAA SEQ IE NO: 4> WS24 GII.4 VP1 codon-optimized coding sequence ATGGCCAGCAGCGACGCCAACCCTAGCGATGGCAGCGCCGCTAATCTGGTGCCCGAGGTGAACAATGAGGTGATGGC CCTGGAACCCGTGGTGGGCGCTGCTATCGCCGCCCCTGTGGCCGGACAGCAGAACGTGATCGACCCTTGGATCCGTA ACAACTTCGTGCAGGCCCCCGGCGGCGAGTTCACCGTCTCCCCTAGAAACGCCCCTGGCGAGATCCTGTGGAGCGCT CCACTGGGCCCTGATCTGAA. CCCCTACCTGAGCCACCTGGCCAGAATGTACAACGGCTACGCCGGAGGATTTGAGGT GCAAGTGATCCTGGCCGGCAACGCCTTCACCGCCGGCAAAGTGATCTTCGCCGCTGTGCCTCCAAACTTCCCTACAG AGGGCCTGAGCCCTTCTCAGGTGACCATGTTCCCACACATCGTGGTCGACGTGCGGCAGCTGGAAOCTGTGCTCATC CCCCTGCCTGACGTGCGGAACAACTTCTACCACTACAACCAGAGCAACGACCCCACAATCAAGCTGATCGCCATGCT GTACACCCCTCTGAGGGCCAA. CAACGCCGGCGACGACGTGTTCACTGTTTCTTGTCGTGTGCTGACCAGACCTTCTC CCGACTTCGACTTTATCTTCCTGGTGCCACCTACAGTGGAAAGCAGAACCAAGCCTTTCAGCGTGCCTGTCCTGACA GTGGAAGAGATGACCAACAGCCGGTTCCCCATCCCTCTGGAAAAGCTGTTCACGGGCCCTTCTTCCGCCTTTGTGGT GCAGCCTCAGA TGGCAGATGCACAACAGACGGCGTGCTGCTGGGCACCACCCAGCTGTCCCCAGTGAATATCTGCACci'TCCGGGGAGATGTGACACACATCACCGGATCCAGAAAC. TACACCA'rGAZiCCI'GGCTAGCCAGAAJ. TGGAACGAC TACGACCCTACCGAGGA TCCCTGCCCCTCTGGGCACCCCTGACTTCGTGGGCAAAATCCAGGGCGTGCTGACCCA GACCACCCGGACCGACGGCTCTACAAGAGGCCACAAGGCCACCGTATACACCGGATCCGCTGATTTTGCTCCCAAGC TGGGCCGCGTGCAGTTTGDAACCGACACCGATAGAGATTTCGAGGCCAATCAGAADACAAAGTTCACACCTGTTGGC GTGATTCAAGACGGCGGCACCACACACAGAAACGAGCCCCAACAGTGGGTGCTGCCAAGCTACAGCGGCAGAAACAC CCACAACGTGCACCTGGCCCCCGCTGTGGCCCCAACATTCCCCGGAGIACAGCTGCTGTTTTTCAGA’IGCACCATGC CTGGCTGTAGCGGATATCCTAACATGGACCTGGACTGCCTGCTGCCTCAGGAGTGGGTGCAGTACTTTTATCAGGAG GCCGCCCCCGCCCAiTCTGATGTGGCTCTGCTCAGATTCGTGAATCCCGATACGGGAAGAGTGCTGTTCGAGTGCA?! GCTTCATAAGAGCGGCTACGTGACCGTGGCCCACACCGGCCAGCACGATTTGGTCATTCCTCCTAATGGCTACTTCA GATTCGACAGCTGGGTCAACCAGTTCTACACACTGGCCCCTATGGGCAACGGAACAGGCCGGCGGAGAGCCGTGTAZi SEQ ID NO: 5> ED150 GI. 1 VP1 codon-optimized coding sequence ATGATGATGGCCAGCAAGGATGCCACCAGCTCTGTGGATGGTGCTTCTGGTGCTGGACAGCTGGTGCCCGAAGTGAA TGCCTCTGATCCCCTGGCCATGGATCCTGTGGCCGGATCTTCTACAGCCGTGGCTACAGCCGGCCAAGTGAACCCTA TCGACCCCTGGATCATCAACAACTTCGTGCAGGCCCCTCAGGGCGAGTTCACAATCAGCCCCAACAATACCCCTGGC GACGTGCTGTTCGACCTGTCTCTGGGCCCTCACCTGAATCCATTTCTGCTGCACCTGAGCCAGATGTACAACGGCTG GGTCGGAAACATGAGAGTGCGGATCATGCTGGCCGGCAATGCCTTTACCGCCGGCAAGATCATCGTGTCTTGCATCCCACCTGGCTTCGGCAGCCAC ACCTGACAATTGCCCAGGCCACACTGTTCCCTCACGTGATCGCTGATGTGCGGACA CTGGATCCTATCGAGGTGCCCCTGGAAGATGTCCGGAATGTGCTGTTCCAC ACAACGACCGGAACCAGCAGACCAT GCGGCTCGTGTGCATGCTGTACACCCCTCTGAGAACAGGCGGCGGAACCGGCGATTCTTTTGTGGTGGCTGGCAGAG TGATGACATGCCCCTCTCCAGACTTCAACTTCCTGTTCCTGGTGCCTCCTACCGTGGAACAGAAAACCCGGCCTTTC ACACTGCCCAACCTGCCTCTGAGCAGCCTGAGCAATTCTAGAGCCCCTCTGCCTATCAGCAGCATGGGCATCAGCCC CGATAACGTGCAGAGCGTGCAGTTCCAGAACGGCAGATGTACCCTGGACGGCAGACTCGTGGGCACCACACCTGTGT CTCTGTCTCACGTGGCCAAGATCCGGGGCACAAGCAATGGCACCGTGATCAACCTGACCGAGCTGGATGGCACCCCA TTTCACCCTTTTGAGGGCCCTGCTCCTATCGGCTTTCCTGATCTCGGCGGCTGCGACTGGCACATCAACATGACACA GT'T'CGGCCACAGCAGCT^AGACACAGTACGACGTGGACACAACCCCTGACACCTT'CGTGCCTCACCTGGGATCCA'rCC AGGCCAATGGCATCGGCAGCGGCAATTATGTGGGCGTGCTGAGCTGGATCAGCCCTCCATCTCACCCTAGCGGATCT CAGGTGGACCTGTGGAAGATCCCCAACTACGGCAGCAGCAT'CACCGAGGCCACACATCTGGCCCCAT'CT'GTGTACCC ACCTGGATTTGGAGAGGTGCTGGTGTTCTTCATGAGCAAGATGCCTGGACCTGGCGCCTACAATCTGCCTTGCCTGC TGCCTCAAGAGTACATCAGCCACCTGGCCTCTGAACAGGCCCCTACAGTTGGAGAAGCCGCACTGCTGCACTACGTG GACCCTGATACCGGCAGAAACCTGGGCGAGTTT AGGCTTACCCCGACGGCTTCCTGACCTGCGTTCCAAATGGCGC CTCTTCTGGACCTCAGCAGCTGCCCATCAATGGCGTGTTCGTGTTTGTGTCCTGGGTGTCCCGGTTCTACCAGCTGA AGC CT GT GGGAACAGC CAGCAGC GOT AGAGGCAGACT GGGCCT GAGAAGATAG SEQ IE NO: 6> ED153 GI1.4 VP1 codon-optimized coding sequence ATGAAGATGGCCAGCTCCGATGCCAATCCTTCCGATGGCTCTGCCGCCAACCTGGTGCCTGAAGTGAACAACGAAGT GATGGCCCTGGAACCTGTCGTGGGAGCCGCTATTGCTGCTCCTGTTGCCGGACAGCAGAACGTGATCGACCCCTGGA TCCGGAACAACTTCGTTCAGGCTCCTGGCGGCGAGTTCACCGTGTCTCCAAGAAATGCCCCTGGCGAGATCCTTTGG AGTGCCCCTCTTGGCCCCGATCTGAACCCTTACCTGTCTCACCTGGCCAGAATGTACAACGGCTACGCTGGCGGCTT CGAGGTGCAAGTGATTCTGGCCGGCAATGCCTTCACCGCCGGCAAAGTGATTTTTGCCGCCGTGCCTCCTAACTTCC CCACCG AGGACTGAGCCCCAGCCAAGTGACCATGTTTCCCCACATCGTGGTGGACGTGCGGCAGCTGGAACCAGTG CTGATTCCTCTGCCTGACGTGCGCAACAACTTCTACCACTACAACCAGAGCAACGACCCCACCATCAAGCTGATCGC CATGCTGTACACCCCTCTGAGAGCCAACAATGCCGGCGACGATGTGTTTACCGTGTCCTGCAGAGTGCTGACCCGGC CTTCTCCTGACTTCGACTTCATCTTCCTGGTGCCACCTACCGTGGAAAGCCGGACCAAGCCTTTTAGCGTGCCCGTG CTGACCGTGGAAGAGATGACCAACAGCAGATTCCCCATTCCTCTGGAAAAGCTGTTCACAGGCCCCAGCAGCGCCTT TGTGGTGCAGCCTCAGAATGGCAGATGCACCACTGATGGCGTGCTGCTGGGAACCACACAGCTGAGCCCTGTGAATAT'CT'GCACCTTCAGAGGCGACG'rGACCCACATCACCGGCAGCAGAAAC'rACACCAT'GAACCTGGCCTCTCAGAACTGG AACGACTACGACCCTACCGAGGAAATCCCTGCTCCTCTGGGCACCCCTGATTTCGTGGGAAAGATTCAGGGCGTGCT GACACAGACCACCAGAACCGATGGCAGCACCAGAGGACACAAGGCCACAGTGTATACCGGCAGCGCCGAT'TTCGCCC CTAAGCTGGGAAGAGTGCAGTTCGAGACAGACACCGACAGAGACTTCGAGGCCAACCAGAACACCAAGTTCACCCCT GTGGGCGTGATCCAGGATGGCGGA CAACCCACAGAAACGAGCCTCAGCAGTGGGT'GCTGCCTAGCTACAGCGGCAG AAACACCCACAATGTGCATCTGGCCCCTGCCGTGGCTCCTACATTTCCTGGCGAACAGCTCCTGTTCTTCCGGTCCA CAATGCC'rGGCTGTAGCGGCTACCCCAACATGGACCTGGAT'T'GCCTGCTGCCTCAAGAATGGGTGCAGTACTTTTAC CAAGAGGCCGCTCCTGCTCAGTCCGACGTGGCCCTGCTGAGATTCGTGAACCCCGATACTGGCCGGGTGCTGTTCGA GT'GCAAGCTGCACAAGAGCGGC'rACGT'GACAGTGGCCCACACAGGACAGCACGACCTGGTCATCCCTCCAAACGGCT ACT T CAGAT T CGACAGCT GGGT CAAC CAGT T CT ACACACT GGC CCCTAT GGGCAAC GGAACAGGCAGAAGAAGGGC C GT C TAG SEQ ID NO: 7> ED180 GII. 17 VP1 codon-optimized coding sequence ATGAAGATGGCCAGCAACGATGCCGCTCCTAGCAATGATGGTGCCGCTGGACTTGTGCCCGAGGGCAACAATGAGAC ACTGCCCCTGGAACXJ / TGTTGCCGGCGCTGCTATTGCTGCTCCTGTGACCGGCCAGAACAACATCATCGACCCCTGGA TCCGGACCAACTTCGTGCAGGCTCCTAACGGCGAGTTCACCGTGTCTCCCAGAAATAGCCCTGGCGAGATCCTGCTG AACCTGGP'ACTGGGCCCCGATCTGAACCCTTATCTGGCCCACCTGAGCCGGATGTACAATGGCTATGCTGGCGGCGT GGAAGTGCAGGTTCTGCTGGCCGGAAATGCCTTTACCGCCGGCAAGATCCTGTTTGCCGCCGTGCCTCCTAACTTCC CCGTGGAATTTCTGAGCCCCGCTCAGATCACCATGCTGCCCCACATCATTGTGGACGTGCGGACACTGGAACCCATC ATGATCCCTCTGCCTGATGTGCGGAACACCTTCTTCCACTACAACAACCAGCCTAACAGCCGGATGCGGCTGGTGGC CATGCTGTACACACCCCTGAGAAGCAATGGCAGCGGCGACGATGTGTTTACCGTGTCCTGCCGGGTGCTGACCAGAC CTACACCTGACTTCGAGTTTACCTACCTGGTGCCTCCAAGCGTGGAAAGCAAGACCAAGCCTTTCAGCCTGCCTATC CTGACACTGAGCGAGCTGACC CAGCAGATTCCCCGTGCCTATCGACAGCCTGTTCACAGCCCAGAACAATGTGCT GCAGGT CCAGT GC CAGAAC GGCAGAT GTACACT GGAT GGC GAGCT GCAGGGCACCACACAACT GOT GCCT AGC GGCA TCTGTGCCTTCAGAGGAAGAGTGACCGCCGAGACAGAC ACCCCGACAAGTGGCACATGCAGCTCCAGAACCTGAACGGCACCACCTACGATCCCACCGATGATGTGCCTGCTCCTCTGGGCACCCCTGACTTTAAAGGCGTGGTGTTTGGCAT GGCCTCTCAGCGGAACGTGGGCAATGATGCCCCTGGCAGCACAAGATCTCACGAGGCCGTGATCAGCACATACAGCC CCAGATTCGTGCCCAAGCTGGGCAGCGTGAACTTCAAGAGCAACGACGACGACTTCCAGCTGCAGCCCACCAGATTC ACACCCGTGGGCATCAACGACGATGGCAATCAGCCCTTCAGACA. GTGGGAGCTGCCTGACTATAGCGGCGTGCTGAC CCTGAACATGAATCTGGCTCCTCCAGTGGCTCCCAACTTTCCTGGCGAACAGCTCCTGTTCTTCCGGTCCAGCGTTC CATGTAGCGGCGGCTACAATCAGGGCATCATCGATTGTCTGATCCCGCAAGAGTGGATCCAGCACTTCTACCAAGAG AGCGCCCCTAGCCAGTCTGAGGTGGCCCTGATCAGATACGTGAACCCCGATACCGGCAGAACCCTGTTCGAGGCCAA GCTGCACAGATCCGGCTACATCACAGTGGCCCACAGCGGCGATTATCCTCTGGTGGTGCCTGCCAACGGCTACTTCA GATTCGACAGCTGGGTCAACCAGTTCTACTCTCTGGCCCCTATGGGCACCGGCAACGGAAGAAGAAGGGCTCAATGA TAA SEQ ID NO: 8> ED181 GII.17 VP1 codon-optimized coding sequence ATGAAAATGGCCTCTAACGACGCCGCTCCTTCTAATGACGGAGCCGCTGGACTGGTGCCCGAGGGCAACAACGAGAC ACTGCCACTGGAACCTGTGGCCGGCGCCGCCATCGCCGCCCCTGTGACAGGCCAGAATAACATCATCGATCCTTGGA TCAGAACAAACTTCGTGCAGGCCCCTAACGGCGAATTCACCGTGTCCCCCAGAAACAGCCCTGGCGAGATCCTGCTG AACCTGGAACTGGGCCCTGACCTGAACCCCTACCTGGCACATCTGAGCCGGATGTACAACGGATACGCCGGCGGAGT GGAAGTGCAGGTGCTGCTGGCCGGAAATGCCTTCACAGCCGGGAAGATCCTGTTCGCCGCCGTGCCTCCAAATTTCC CCGTGGAATTCCTGAGCCCCGCCCAGATCACCATGCTGCCTCACATCATCGTGGACGTGCGGACACTGGAACCAATT ATGATCCCTCTGCCTGACGTGCGGAACACCTTCTTCCACTACAACAACCAGCCTAATTCTAGAATGAGACTGGTCGC CATGCTGTACACCCCACTGAGATCCAACGGCTCTGGCGACGACGTGTTCACCGTCAGCTGCAGAGTGCTGACACGCC CCACCCCGGACTTTGAGTTTACATATCTGGTGCCCCCCAGCGTGGAAAGCAAGACCAAGCCTTTCAGCCTGCCTATC CTGACCCTCAGCGAGCTGACCAACAGCAGATTCCCCGTCCCCATCGACTCCCTGTTCACCGCCCAGAACAACGTGCT GCAGGTGCAATGTCAGAACGGCAGATGCACCTTGGATGGAGAACTGCAAGGCACCACCCAGCTGCTGCCCTCCGGCA TCTGCGCCTTTAGAGGCAGAGTGACCGCCGAGACAGACAACCCTGACAAGTGGCACATGCAGCTGCAAAACCTGAAC GGCACAACATACGACCCTACCGATGACGTGCCTGCTCCTCTGGGAACACCTGATTTCAAGGGCGTCGTCTTCGGCAT GGCCTCTCAGAGAAACGTGGGCAACGACGCCCCTGGTAGCACCAGAAGCCACGAGGCTGTGATCAGCACCTACTCCC CTAGATTCGTGCCCAAGCTGGGCAGCGTGAACTTCAAAAGCAATGATGACGACTTCCAGCTTCAGCCTACCCGGTTC ACCCCTGTGGGCATCAACGATGATGGCAACCAGCCATTCAGACAGTGGGAGCTGCCCGACTACTCTGGCGTGCTGAC CCTGAACATGAACCTGGCCCCTCCAGTTGCTCCTAACTTCCCTGGAGAGCAGCTGCTGTTTTTCAGAAGCAGCGTGC CATGTAGCGGCGGCTACAACCAGGGCATCATTGACTGCCTGATCCCCCAGGAGTGGATCCAGCACTTCTACCAGGAG AGCGCCCCTAGCCAGAGCGAGGTGGCCCTGATCCGCTACGTGAACCCCGATACAGGCCGGACCCTGTTTGAGGCCAA GCTGCACAGAAGCGGCTACATCACCGTGGCCCACAGTGGCGATTATCCTCTGGTGGTGCCTGCTAATGGCTACTTCC GGTTCGACAGCTGGGTCAATCAATTTTACAGCCTGGCTCCAATGGGCACTGGAAATGGCCGGAGAAGGGCCCAGTGA TAA SEQ ID NO: 9> Norwalk GI 1 VP1 amino acid sequence MMMASKDATSSVDGASGAGQLVPEVNASDPLAMDPVAGSSTAVATAGQVNPIDPWIINNFVQAPQGEFTISPNNTPG DVLFDLSLGPHLNPFLLHLSQMYNGWVGNMRVRIMLAGNAFTAGKIIVSCIPPGFGSHNLTIAQATLFPHVIADVRT LDPIEVPLEDVRNVLFHNNDRNQQTMRLVCMLYTPLRTGGGTGDSFWAGRY'MTCPSPDFNFLFLVPPTVEQKTRPF TLPNLPLSSLSNSRAPLPISSMGISPDNVQSVQFQNGRCTLDGRLVGTTPVSLSHVAKIRGTSNGTVINLTELDGTP FHPFEGPAPIGFPDLGGCDWHINMTQFGHSSQTQYDVDTTPDTFVPHLGSIQANGIGSGNYVGVLSWISPPSHPSGS QVDLWKIPNYGSS ITEATHLAPSVYPPGFGEVLVFFMSKMPGPGAYNLPCLLPQEYISHLASEQAPTVGEAALLHYV DPDTGRNLGEFKAYPDGFLTCVPNGASSGPQQLPINGVFVFVSWVSRFYQLKPVGTASSARGRLGLRR*SEQ ID NO: 10> Sydney Gii.4 VP1 amino acid sequence MKMASSDANPSDGSAANLVPEVNNEVMALEPWGAAIAAPVAGQQNVIDPWIRNNFVQAPGGEFTVSPRNAPGEILW SAPLGPDDNPYLSHIARMYNGYAGGFEVQVILAGNAFTAGKVI FAAVPPNFPTEGLSPSQVTMFPHIWDVRQLEPV LIPLPDVRNNFYHYNQSNDPTIKLIAMLYTPLRANNAGDDVFTVSCRVLTRPSPDFDFIFLVPPTVESRTKPFSVPV LTVEEMTNSRFPI PLEKLFTGPSSAFVVQPQNGRCTTDGVLLGTTQDSPVNICTFRGDVTHITGSRNYTMNLASQNW NDYDPTEEIPAPLGTPDFVGKIQGVLTQTTRTDGSTRGHKATVYTGSADFAPKLGRVQFETDTDRDFEANQNTKFTP VGVIQDGGTTHRNEPQQWLPSYSGRNTHNVHLAPAVAPTFPGEQLLFFRSTMPGCSGYPNMDLDCLLPQEWVQYFYQEAAPAQSDVALLRFVNPD'TGRVLFECKLHKSGYVTVAHTGQHDLVIPPNGYFRFDSWNQFYTLAPMGNGTGRRRA V* SEQ IE> NO: 11> GII.17 amino acid sequence MKMASNDA^PSNDGAAGLVPEGNNETLPLEPVAGA^IAIPVTGQNNIIDPWIRTNFVQAPNGEFTVSPRNSPGEILL NLELGPDLNPYLAHLSRMYNGYAGGVEVQVLLAGNAFTAGKILFAAVPPNFPVEFLSPAQITMLPHIIVDVRTLEPI MIPLPDVRNTFFHYNNQPNSRMRLVAdLYTPLRSNGSGDDVFTVSCRVLTRPTPDFEFTYLVPPSVESKTKPFSLPI LTLSELTNSRFPVPIDSLFTAQNNVLQVQCQNGRCTLDGELQGTTQLLPSGICAFRGRVTAETDNPDKWHMQLQNLN GTTYD'PTDDVPAPLGTPDFKGWFGRL SQRNVGNDAPGSTRSHEAVISTYSPRFVPKLGSVNFKSNDDDFQLQPTRF TPVGINDDGNQPFRQWELPDYSGVLTLNMNLAPPVAPNFPGEQLLFFRSSVPCSGGYNQGIIDCLIPQEWIQHFYQE SAPSQSEVALIRYVNPDTGRTLFEAKLHRSGYITVAHSGDYPLWPANGYFRFDSWVNQFYSLAPMGTGNGRRRAQ*SEQ ID NO: 12: TLR-3 agonist sequence GCCACTGCAGGAAAlGATATGGGCTGA rACGGATCCGTATTCAGCCCATATCGTTTCSEQ ID NO: 13: TLR-3 agonist sequence GAAACGATATGGGCTGAATACTTAAGTATTCAGCCCATATCGTTTC SEQ ID NO: 14: TLR-3 agonist sequence CGGGCCCCCCCTCGAGGTCGACGGTATCGATAAGCTTGATATCGAATTCGCCCTTAGATATCGTCGACGCCCAGCAf CCCAAGGCGGCCAACGCCAAAACTCTCCCTCCTCCTCTTCCTCAATCTCGCTCTCGCTCTTTTTTTTTTTCGCAAAA GGAGGGGAGAGGGGGTAAAAAAATGCTGCACTGTGCGGCGAAGCCGGTGAGTGAGCGGCGCGGGGCCAATCAGCGTG CGCCGTTCCGAAAGTTGCCTTTTATGGCTCGAGCGGCCGCGGCGGCGCCCTATAAAACCCAGCGGCGCGACGCGCCA CCACCGCCGAGACATCGATGATATCTAAAGGGCGAATTCCTGCAGCCCGGGGGATCCACTAGTCTAGATGCATGCTC GAGCGGCCGCCAGTGTGATGGATATCTGCAGAATTCGCCCTTCAGCTGCGGATCCATTCGCCATTCAGGCTGCGCAA CTGTTGGGAAGGGCGATCGGTGCGGGCCTCTTCGCTATTACGCCAGCTGGCGAAAGGGGGATGTGCTGCAAGGCGAT TAAGTTGGGTAACGCCAGGGTTTTCCCAGTCACGACGTTGTAAAACGACGGCCAGTGAATTGTAATACGACTCACTA TAGGGCGAATTGGGTACCGGGCCCCCCCTCGAGGTCGACGGTATCGATAAGCTTGATATCGAATTCCTGCAGCCCGG GGGATCCACTAGTTTCTAGAAATAAAATATCTTTATTTTCATTACATCTGTGTGTTGGTTTTTTGTGTGGCGGCCGC CACCGCGGTGGAGCTATCGAATTCAAGCTTGTCGACTCGAAGATCCTAGACTAxGTGGATCCCCCGGGCTGCAGGAAT TCGCCCTTTAGATATCATCGATGTCTCGGCGGTGGTGGCGCGTCGCGCCGCTGGGTTTTATAGGGCGCCGCCGCGGC CGCTCGAGCCATAAAAGGCAACTTTCGGAACGGCGCACGCTGATTGGCCCCGCGCCGCTCACTCACCGGCTTCGCCGC7\CAGTGCAGCATTTTTTTACCCCCTCTCCCCTCCTTTTGCGAAAAAAAAAAAG7\GCGAGAGCGAGATTGAGGAAG7\ GGAGGAGGGAGAGTTTTGGCGTTGGCCGCCTTGGGGTGCTGGGCGTCGACGATATCTAAGGGCGAATTCGATATCAA GCTTATCGATACCGTCGACCTCGAGGGGGGGCCCG SEQ ID NO: 15: TLR-3 agonist sequence CGGGCCCCCCCTCGAGGTCGACGGTATCGATAAGCTTGATATCGAATTCGCCCTTAGATATCGTCGACGCCCAGCAC CCCAAGGCGGCCAACGCCAAAACTCTCCCTCCTCCTCTTCCTCAATCTCGCTCTCGCTCTTTTTTTTTTTCGCAAAA GGAGGGGAGAGGGGGTAAAAAAATGCTGCACTGTGCGGCGAAGCCGGTGAGTGAGCGGCGCGGGGCCAATCAGCGTG CGCCGTTCCGAAAGTTGCCTTTTATGGCTCGAGCGGCCGCGGCGGCGCCCTATAAAACCCAGCGGCGCGACGCGCCA CCACCGCCGAGACATCGATGATATCTAAAGGGCGAATTCCTGCAGCCCGGGGGATCCACTAGTCTAGATGCATGCTC GAGCGGCCGCCAGTGTGATGGATATCTGCAGAATTCGCCCTTCAGCTGCGGATCCATTCGCCATTCAGGCTGCGCAA CTGTTGGGAAGGGCGATCGGTGCGGGCCTCTTCGCTATTACGCCAGCTGGCGAAAGGGGGATGTGCTGCAAGGCGAT TAAGTTGGGTAACGCCAGGGTTTTCCCAGTCACGACGTTGT7WVACGACGGCCAGTGAATTGTAATACGACTCACTA TAGGGCGAATTGGGTACCGGGCCCCCCCTCGAGGTCGACGGTATCGATAAGCTTGATATCGAATTCCTGCAGCCCGG GGGATCCACTAGTTTCTAGAAATAA ATATCTTTATTTTCATTACATCTGTGTGTTGGTTTTTTGTGTGGCGGCCGC C CCGCGGTGGAGC TCGAATTCAZ\GC GTCGACTCGAAG TCGT C C GGAPLGTGACA. TTT CGCGCGGTTT TAGGCGGATGTTGTAGTAAATTTGGGCGTAACCGAGTAAGATTTGGCCATTTTCGCGGGAAAACTGAATAAGAGGAA.GTGAAATCTGAATAATTTTGTGTTACTCATAGCGCGTAATACTGGTACCGGGCCCCCCCTCGAGGTCGACGGTATCG ATAAGCTTGATATCGAATTCGCCCTTAGATATCGTCGACGCCCAGCACCCCAAGGCGGCCAACGCCAAAACTCTCCC TCCTCCTCTTCCTCAATCTCGCTCTCGCTCTTTTTTTTTTTCGCAAAAGGAGGGGAGAGGGGGTAAAAAAATGCTGC ACTGTGCGGCGAAGCCGGTGAGTGAGCGGCGCGGGGCC ATCAGCGTGCGCCGTTCCGAAAGTTGCCTTTTATGGCT CGAGCGGCCGCGGCGGCGCCCTATAAAACCCAGCGGCGCGACGCGCCACCACCGCCGAGAC TCGATGATATCTAAA GGGCGAATTCCTGCAGCCCGGGGGATCCACTAGTCTAGAACTAGTGGATCCCCCGGGCTGCAGGAATTCGATATCAA GCTTATCGATACCGTCGACCTCGAGGGGGGGCCCGGTACCCAATTCGCCCTATAGTGAGTCGTATTACAATTCACTG GCCGTCGTTTTACAACGTCGTGACTGGGAAAACCCTGGCGTTACCCAACTTAATCGCCTTGCAGCACATCCCCCTTT CGCCAGCTGGCGTAATAGCGAAGAGGCCCGCACCGATCGCCCTTCCCAACAGTTGCGCAGCCTGAATGGCGAATGGA TCCGCAGCTGAAGGGCGAATTCTGCAGATATCCATCACACTGGCGGCCGCTCGAGCATGCATCTAGAAATAAAATAT CTTTATTTTCATTACATCTGTGTGTTGGTTTTTTGTGTGGCGGCCGCC CCGCGGTGGAGCTA SEQ ID NO: 16: TLR-3 agonist sequence GATGGTGCTTCAAGCTAGTACTTAAGTACTAGCTTGAAGCACCATC SEQ ID NO: 17: TLR-3 agonist sequenceGAT GGT GCT T CAAGCT GT CGGAT 0 CGTACTAGCT T GAAGCACCAT CSEQ ID NO: 18: TLR-3 agonist sequence GAAACGATATGGGCTGAATACGGATCCGTATTCAGCCCATATCGTTTC SEQ ID NO: 19: TLR-3 agonist sequence CCTAATAATTATCAAAATGTGGATCCACATTTTGATAATTATTAGG SEQ ID NO: 20: TLR-3 agonist sequenceC CT AAT AAT TAT C AAAAT GT AAT TAG AT T T T GAT AAT TAT T AGG SEQ ID NO: 21: rAd-CS186A8 nucleotide sequence1 taacatcatc aataatatac cttattttgg attgaagcca atatgataat gagggggtgg 61 agtttgtgac gtggcgcggg gcgtgggaac ggggcgggtg acgtagtagt gtggcggaag 121 tgtgatgttg caagtgtggc ggaacacatg taagcgacgg atgtggcaaa agtgacgttt 181 ttggtgtgcg ccggtgtaca caggaagtga caattttcgc gcggttttag gcggatgttg 241 tagtaaattt gggcgtaacc gagtaagatt: tggc:catttt cgcgggaaaa ctg ataaga 301 ggaagtgaaa tctgaataat tttgtgttac tcatagcgcg taatactgct agagatctgg 361 cgaaaggggg atgtgctgca aggcgattaa gttgggtaac gccagggttt tcccagtcac 421 gacgttgtaa aacgacggcc agtgaattgt aatacgactc actatagggc gaattgggta 481 ctggccacag agcttggccc attgcatacg ttgtatccat atcataatat gtacatttat 541 attggctcat gtccaacatt accgccatgt tgacattgat tattgactag ttattaatag 601 taatcaatta cggggtcatt agttcatagc ccatatatgg agttccgcgt tacataactt 661 acggtaaatg gcccgcctgg ctgaccgccc, aacgaccccc gcccattgac gtcaataatg 721 acgtatgttc ccatagtaac gccaataggg actttccatt gacgtcaatg ggtggagtat 781 ttacggtaaa ctgcccactt ggcagtacat caagtgtatc atatgccaag tacgccccct 841 attgacgtca atgacggtaa atggcccgcc tggcattatg cccagtacat gaccttatgg 901 gactttccta cttggcagta catctacgta ttagtcatcg ctattaccat ggtgatgcgg 961 ttttggcagt acatcaatgg gcgtggatag cggtttgact cacggggatt tccaagtctc 1021 caccccattg acgtcaatgg gagtttgttt tggcaccaaa atcaacggga ctttccaaaa 1081 tgtcgtaaca actccgcccc attgacgcaa atgggcggta ggcgtgtacg gtgggaggtc 1141 tatataagca gagctcgttt agtgaaccgt: cagatcgcct: ggagacgcca tccacgctgt 1201 tttgacctcc atagaagaca ccgggaccga tccagcctga ctctagccta gctctgaagt1261 tggtggtgag gccctgggca ggttggtatc aaggttacaa gacaggttta aggagaccaa 1321 t ga ctgg gc tgtggag acagagaaga ctcttgggtt tctgataggc c gactctc 1381 tctgcctatt ggtctatttt cccaccctta ggctgctggt ctgagcctag gagatctctc 1441 gaggtcgacg gtatcgatgg gtacggtacc gccaccatga tgatggcgag caaagaeget 1501 acatcctccg tggatggggc ctctggagca ggtcagctgg tgccggaggt gaacgcatca 1561 gatcctcttg ctatggaccc agtggcagga agcagtactg cagtcgctac tgctggacaa 1621 gtaaatccca tcgatccctg gatcatcaat aacttcgtgc aggccccaca aggcgaattt 1681 actatttccc ccaacaacac gcctggcgat gtgttgttcg atctgtctct tggcccccat 1741 ctgaacccct ttctgttgca tctctcccag atgtacaatg gctgggtggg caatatgcgc 1801 gtgcgcatta tgttggccgg taacgcgttt acagctggaa aaataatcgt gagctgcatt 1861 cctcccggct tcggttccca taatctgaca atagcgcagg ctaccctgtt ccctcacgtg 1921 a i-cgcggatg tgagaacact tgatcccata gaggtgcctc tggaagacgt gagaaatgtc 1981 t tg cc t t tg eeg gaatcaacaa ac tgaggc t gtgtgcat g gtacaca 2041 cctctgcgga egggeggegg aacaggggac tcatttgtag tggcaggaag agtgatgacc 2101 tgcccttctc ccgac caa tttcctgttt ttggttcctc ccac gtcga gcagaagact 2161 aggccattta ccctgcccaa tctcccgctt agctcactgt ctaattcaag agcaccgctg ccaa tttctt ca tgggcat ttccccggac a tgtgcagt ccgttcaatt cc gaacggc 2281 aggtgtacgc tggatggcag acttgtcggc actacaccgg tcagcctctc acacgttgcc 2341 a ttc gg gtac ccaa cggcacggtc atcaacttga ccg gctgga cgggaccccg 2401 ttccacccct ttgagggccc cgctcctatc gggtttcccg atctgggagg gtgtgattgg 2461 c ca tcaaca tgacacagtt tgggca gc tc c gacgc agtacgacgt cg t cc cc 2521 cctgacacat tcgtgccgca tctcggctca atccaggcaa acggcatagg gagtggtaat 2581 tatgtcggtg tcttgagttg gatctctccg ccctctcacc cttccggttc ccaagtagac 2641 ctctggaaga tccccaatta cggctcctct atcaccgagg ccacccactt ggccccatcc 2701 gtctatcccc caggattcgg ggaggtactc gttttcttca cgagtaagat gcctggtcct 2761 ggcgcctaca atetgeettg cttgttgccc caggagtaca ttagccacct ggcctctgaa 2821 caggccccca ccgtgggaga agccgctttg ttgc CL ttacg tcgaccccga caccggtaga 2881 aacctgggag agtttaaagc atatcctgat gggttcctta cctgcgtgcc caatggcgca 2941 tcatctggcc cccagcagct gccgatcaat ggcgttttcg tctttgtgtc ctgggtatcc 3001 cgcttctacc agetgaagee ggttggcaca gcctcatcag cacgcggcag actgggcctc 3061 agaagataac gateggatat cgctagcgta ccggcggccg ccctattcta tagtgtcacc 3121 taaa gct g ageteget a tea gee cga ctgtgccttc tagttgcca ccatctgttg 3181 tttgcccctc ccccgtgcct tccttgaccc tggaaggtgc cactcccact gtcctttcct 3241 aataaaatga gga a ge tcgc ttgtc tgagtaggtg tcattctatt ctggggggtg 3301 gggtggggca ggacagcaag ggggaggatt gggaagacaa tagcaggcat gctggggatg 3361 cgg gggctc tatggettet gag gc gg g cc aagc ttacgcgtta g attaata 3421 gtaatcaatt acggggtcat tagttcatag cccatatatg gagttccgcg ttacataact 3481 t cggtaaat ggcccgcctg gctg ccgcc caacgacccc cgcccattga cgtcaataat 3541 gacgtatgtt cccatagtaa cgccaatagg gactttccat tgacgtcaat gggtggagta 3601 tttacggtaa actgcccact tggcagtaca tcaagtgtat catatgccaa gtacgccccc 3661 tattgacgtc aatgacggta aatggcccgc ctggcattat gcccagtaca tgaccttatg 3721 ggactttcct acttggcagt acatctacgt attagtcatc gctattacca tggtgatgcg 3781 gttttggcag tacatcaatq ggcgtggata gcggtttgac tcacggggat ttccaagtct 3841 ccaccccatt gaegteaatg ggagtttgtt ttggcaccaa aatcaacggg actttccaaa 3901 atgtcgtaac aactccgccc cattgacgca aatgggcggt aggcgtgtac ggtgggaggt 3961 c i. i_a taaqc agagctggtt tagtgaaccg tcagatccgc tagagatatc gggccactgc 4021 aggaaacgat atgggctgaa tacggatccg tattcagccc atatcgtttc tctagagagc 4081 tcagtactaa taaaatatet ttattttcat tacatctgtg tgttggtttt ttgtgtgaat 4141 cgatagtact aaca taeget ctccatctcg agcctaagc t: gtcg ctcg aagatctggg 4201 cgtggttaag ggtgggaaag aatatataag gtgggggtct tatgtagttt tgtatctgtt 4261 gc gc gc egee gee ee atgagcacca actcgtttga t gaagcatt g gage te t 4321 atttgacaac gcgcatgccc ccatgggccg gggtgcgtca gaatgtgatg ggctccagca 4381 ttg t tcg ccccg cctg cccgcaaact ct act acct gacct cgag accgtgtctg 4441 gaacgccgtt ggagaetgea gcctccgccg ccgcttcagc cgctgcagcc accgcccgcg 4501 gga t: gtgac tgactttgct ttcctgagcc cgcttgca g cagtgcagct tcccgttcat 4561 ccgcccgcga tgacaagttg acggctcttt tggcacaatt ggattctttg acccgggaac 4621 ttaat tcgt ttctcagcag ctgttggatc t cgccagc ggtttctgcc etgaaggett4681 cctcccctcc caatgcggtt taaaacataa at O. O. O. d d d C C agactctgtt tggatttgga 4741 caagcaagt gtc gc gt ett a t tag gggtt tgcg egegeggtag gcccgggacc 4801 agcggtctcg gtcgttgagg gtcctgtgta ttttttccag gaegtggtaa aggtgactct 4861 ggatgttcag atacatgggc ataagcccgt ctctggggtg gaggtagcac cact caqaq 4921 cttcatgctg cggggtggtg ttgtagatga tccagtcgta gcaggagcgc tgggcgtggt 4981 gcctaaaaat gtctttcagt ageaagetga ttgccagggg caggcccttg gtgtaagtgt 5041 ttacaaagcg gttaagctgg gatgggtgca tacgtgggga tatgagatgc atcttggact 5101 gtatttttag gttggctatg ttcccagcca tatccctccg gggattcatg cgt eaqaa 5161 ccaccagcac agtgtatccg gtgcacttgg gaaatttgtc atgtagetta gaaggaaatg 5221 cgtggaagaa cttggagacg cccttgtgac ctccaagatt ttcc CL tgcat tcgtccataa 5281 tgatggcaat gggcccacgg gc.ggcggcct gggegaagat atttctggga tcactaacgt 5341 c a uagtt tq ttccaggatg agategteat aggccatttt tacaaagcgc gggcggaggg 5401 gccagactg eggtataatg gttcca teeg gcccaggggc gtagttaccc tcacagattt 5461 gcatttccca eget tgagt tcagatgggg ggatcatgtc tacctgcggg gegatgaaga 5521 aaacggt tc cggggtaggg gaga c age gggaagaaag caggttcc g age age g eg 5581 acttaccgca gccggtgggc ccgtaaatca cacctattac cggctgcaac tggtagtt 0.0.5641 gaga get gca gc gccg ca tccc gagca ggggggccac cgttaagc a tgtccctga 5701 ctcgcatgtt ttccctgacc aaatccgcca gaaggcgctc gccgcccagc gatagcagtt 5761 e tgeaagga agcaaagttt ttcaacggtt tgagaccg c cgccgtaggc atgctt tga 5821 gcgtttgacc aagcagttcc aggcggtccc acagctcggt cacctgctct acggcatctc 5881 ga ee ge t atc cc cgt ttcgcgggt t ggggcggc cgctgtacg gca g tag teg 5941 gtgctcgtcc agacgggcca gggtcatgtc tttccacggg cgcagggt.ee tegteagegt 6001 ag ugggte aeggtgaagg ggtgcgctcc gggctgcgcg ctggccaggg tgegettgag 6061 gctggtcctg ctggtgctga agcgctgccg gtcttcgccc tgegegtegg ccaggtagca 6121 tttgaccatg gtgtcatagt ccagcccctc egeggegtgg cccttggcgc gcagcttgcc 6181 ettggaggag gcgccgcacg aggggcagtg cagacttttg agggegtaga gcttgggcgc 6241 gagaaatacc gattccgggg agtaggcatc cgcgccgcag gccccgcaga cggtctcgca 6301 ttccacgagc caggtgagct ctggccgttc ggggt.caaaa accaggtttc ccccatgctt 6361 tttgatgegt ttcttacctc tggtttccat gageeggtgt ccacgctcgg tgaegaaaag 6421 gctgtccgtg tccccgtata cagacttgag aggcctgtcc tegageggtg ttccgcggtc 6481 ctcctcgtat agaaactcgg accactctga gacaaaggct cgcgtccagg C C cl Cj C cl C Q o. o.6541 ggaggetaag tgggaggggt agegg egt t gtccac agg gggtccactc gc tccagggt 6601 gtgaagacac atgtcgccct cttcggcatc aaggaaggtg attggtttgt aggtgtaggc 6661 cacg gaccg gg g t teetg aaggggggct a aaaagggg gtgggggcgc gt cgtcctc 6721 actctcttcc gcatcgctgt etgegaggge cagctgttgg ggtgagtact ccctctg o. o. o.6781 agcgggcatg act ctgcgc taaga tgte agtttccaaa aacgaggagg a t ttgatatt 6841 cacctggccc geggtgatge ctttgagggt ggccgcatcc atctggtcag aaaagacaat 6901 c tt g tg ea age ttgg tggcaaacga cccgtagagg gcgttggaca gcaact ggc 6961 gatggagege agggtttggt ttttgtcgcg atc.ggcgcgc tccttggccg cgatgtttag 7021 etgeaegtat tcgcgcgcaa cgcaccgcca ttcgggaaag acggtggtgc getegteggg 7081 caccaggtgc acgcgccaac. cgcggttgtg cagggtgaca aggteaaege tggtggctac 7141 ctctccgcgt aggegetegt tggtccagca gaggeggeeg cccttgcgcg agcagaatqq 7201 cggtaggggg tetagetgeg tctcgtccgg ggggt.ctgcg tccacggtaa agaccccggg ‘7261 cagcaggcgc gegtegaagt agtetatett gcatccttgc aagtctagcg cctgctgcca 7321 tgcgcgggcg gcaagcgcgc getegtatgg gttgagtggg ggaccccatg gcatggggtg 7381 ggtgagcgcg gaggcgtaca tgccgcaaat gtcgtaaacg tagaggggct c cet a tat 7441 tccaagatat gtagggtagc atcttccacc geggatgetg gcgcgcacgt aategtatag 7501 ttegtgegag ggagegagga ggtcgggacc gaggttgeta cgggcgggct gctctgctcg 7561 gaagactatc gee tgaaga tggca g ga g tgga ga t a tggttggac gctggaagac 7621 gttgaagctg gcgtctgtga gacctaccgc gtcacgcacg aaggaggegt aggagtegeg 7681 cage ttgttg accagc cgg cgg gacc tg cacgtc agg gcgcagtagt ccagggtttc 7741 ettgatgatg teataettat cctgtccctt ttttttccac agetegeggt tgaggacaaa 7801 c ct cgcgg tet tccagt actcttggat cggaaacccg tcggcctccg aacggtaaga 7861 gcctagcatg tagaactggt tgacggcctg gtaggcgcag catccctttt etaegggtag 7921 cgcgtatgcc gcgcggcc teeggagega ggtgtggg g agcgcaaagg tgtccctgac 7981 catgactttg aggtactggt atttgaagte agtgtcgtcg catccgccct gctcccagag 8041 caaaaagtcc g gege tttt tggaaegegg a ttggcagg gegaaggtga catcgttgaa8101 gagtatcttt cccgcgcgag gcataaagtt gcgtgtgatg cggaagggtc ccggcacctc 8161 ggaacggttg tta ttacct gggcggcgag cacg tctcg tcaaagccgt tgatgttgtg 8221 gcccacaatg taaagttcca agaagcgcgg gatgcccttg atggaaggca attttttaag 8281 ttcctcgtag gtgagctctt caggggagct gagcccgtgc tctgaaaggg cccagtctgc 8341 aagatgaggg ttggaagcga cgaatgagct ccacaggtca cgggccatta gcatttgcag 8401 gtggtcgcga aaggtcctaa actggcgacc tatggccatt ttttctgggg tgatgcagta 8461 gaaggtaagc gggtcttgtt cccagcggtc ccatccaagg ttcgcggcta ggtctcgcgc 8521 ggcagtcact agaggctcat ctccgccgaa cttc CL tgacc agcatgaagg gcacgagctg 8581 cttcccaaag gcccccatcc aagtataggt ctctacatcg taggtgacaa agagacgctc 8641 ggtgcgagga tgcgagccga tcgggaagaa ctggatctcc cgccaccaat tggaggagtg 8701 gctattgatg tggtgaaagt agaagtccct gcgacgggcc gaacactcgt gctggctttt 8 61 g uaaaaacgt gcgcagtact ggcagcggtg cacgggctgt acatcctgca cgaggttgac 8821 c gacgaccg cgcacaagga agcagag gg gaatttg gc ccctcgcctg gcgggtttgg 8881 ctggtggtct tctacttcgg ctgcttgtcc ttgaccgtct ggctgctcga ggggagttac 8941 ggtggatcgg accaccacgc cgcgcg gcc caaagtccag atgtccgcgc geggeggteg 9001 gagcttgatg acaacatcgc gcagatggga gctgtccatg gtctggagct cccgcggcgt 9061 cagg caggc ggg gctcct gcaggt t: ac ctcgc t ga cgggtcaggg egeggget g 9121 atccaggtga tacctaattt ccaggggctg gttggtggcg gcgtcgatgg ettgeaagag 9181 gccgcatccc cgcggcgcga ctacggtacx: gcgcggcggg cggtgggccg cgggggtgtc 9241 cttggatgat gcatctaaaa gcggtgacgc gggcgagccc ccggaggtag ggggggctcc 9301 ggacccgccg ggagaggggg caggggcacg tcggcgccgc gcgcgggcag gagctggtgc 9361 tgcgcgcgta ggttgctggc gaacgcgacg acgcggcggt tgatctcctg aatctggcgc 9421 ctctgcgtga agacgacggg cccggtgagc ttgaacctga aagagagttc gacagaatca 9481 atttcggtgt cgttgacggc ggcctggcgc aaaatctcct gcacgtctcc tgagttgtct 9541 tgataggcga tctcggccat gaactgctcg atctcttcct cctggagatc tccgcgtccg 9601 gctcgctcca cggtggcggc gaggtcgttg gaaatgcggg ccatgagctg egagaaggeg 9661 ttgaggcctc cctcgttcca gacgcggctg tagaccacgc ccccttcggc atcgcgggcg 9721 cgcatgacca cctgcgcgag attgagctcc acgtgccggg cgaagacggc gtagtttcgc 9781 aggcgctgaa agaggtagtt gagggtggtg gcggtgtgtt ctgccacgaa gaagtacata 9841 acccagcgtc gcaacgtgga ttcgttgata tcccccaagg cctcaaggcg ctccatggcc 9901 tcgtagaagt ccacggcgaa gttgaaaaac tgggagttgc gcgccgacac ggttaactcc 9961 tcc tccagaa gacgg tgag ctcggcgac gtgtcgcgca cctcgcgctc aaaggctaca 10021 ggggcctctt cttcttcttc aatctcctct tccataaggg cctccccttc ttcttcttct 10081 ggcggcggtg ggggaggggg gacacggcgg cgacgacggc gcac egggag gcggtcgaca 10141 aagcgctcga tcatctcccc gcggcgacgg cgcatggtct eggtgaegge gcggccgttc 10201 tcgcgggggc gcagttggaa gacgccgccc gtc tgtccc ggttatgggt ggcgggggg 10261 ctgccatgcg gcagggatac ggcgctaacg atgcatctca acaattgttg tgtaggtact 10321 ccgccgccga gggacc g g cg gtccgca tcgaccgga t: cggaaaacct ctcgagaaag 10381 gcgtctaacc agtcacagtc gcaaggtagg ctgagcaccg tggcgggcgg cagcgggcgg 10441 cggtcggggt tgtttctggc ggaggtgctg ctgatgatgt aattaaagta ggcggtcttg 10501 agacggcgga tggtcgacag aagcaccatg tccttgggtc cggcctgctg aatgcgcagg 10561 cggtcggcca tgccccaggc ttcgttttga catcggcgca ggtctttgta gtagtcttgc 10621 atgagccttt ctaccggcac ttcttcttct ccttcctctt gtcctgcatc tettgeatet 10681 atcgctgcgg cggcggcgga gtttggccgt aggtggcgcc ctcttcctcc catgcgtgtg 10741 accccgaagc ccctcatcgg ctgaagcagg gctaggtcgg cgacaacgcg ctcggctaat 10801 atggcctgct gcacctgcgt gagggtagac tggaagtcat ccatgtccac aaagcggtgg 10861 tatgcgcccg tgttgatggt gtaagtgcag ttggccataa cggaccagtt aacggtctgg 10921 tgacccggct gcgagagctc ggtgtacctg agacgcgagt aagccctcga gtcaaatacg 10981 t gtcgttgc aagtccgcac caggtactgg tatcccacca a a gtgegg eggeggetgg 11041 cggtagaggg gccagcgtag ggtggccggg gctccggggg egagatette caacataagg 11101 cga tg t tc cgtagatgta cctggaca c c ggtg tgc eggeggeggt gg gg ggcg 11161 cgcggaaagt cgcggacgcg gttccagatg ttgcgcagcg gcaaaaagtg ctccatggtc 11221 gggacgctct ggccgg cag gcgcgcgc tcgttgacgc etagegtge aaaaggagag 11281 cctgtaagcg ggcactcttc cgtggtctgg tggataaatt cgcaagggta teatggegga 11341 cgaccggggt tcg gccccg tatccggccg tccgccgtga tccatgcggt accgcccgc 11401 gtgtcgaacc caggtgtgcg acgtcagaca acgggggagt gctccttttg gcttccttcc 11461 aggcgcggcg gctgc gcgc tagctttttt ggccactggc cgcgcgc gc gtaagcggtt11521 d Cj Cj CLCj Cj 333 gcgaaagcat taagtggctc gctccctgta gccggagggt tattttccaa 11581 ggg gagtc gcgggacccc eggttegag ctcggaccgg ccggactgcg gcgaacgggg 11641 gtttgcctcc ccgtcatgca agac.c.c.cgct tgcaaattcc tccggaaaca gggaegagee 11701 ccttttttgc ttttcccaga tgcatccggt gctgcggcag atgcgccccc ctcctcagca 11761 gcggcaagag caagagcagc ggcagacatg cagggcaccc tcccctcctc ctaccgcgtc 11821 aggaggggcg acatccgcgg ttgaegegge agcagatggt gattacgaac ccccgcggcg 11881 ccgggcccgg cactacctgg aettggagga gggcgagggc ctggcgcggc taggagegee 11941 ctctcctgag cggcacccaa gggtgeaget gaagegtgat aegegtgagg cgtacgtgcc 12001 gcggcagaac c.tgtttcgcg accgcgaggg agaggagc.ee gaggagatgc gggatcgaaa 12061 gttccacgca gggegegage tgcggcatgg cctgaatcgc gagcggttgc tgegegagga 12121 ggactttgag cccgacgcgc gaac.c.gggat tagtcccgcg cgcgcacacg tggcggccgc 12181 cgacct ta accgcatacg ageagaeggt gaaccaggag attaaettte12241 taacaaccac g geg aege ttgtggcgcg egaggaggtg gctataggac tgatgeatet 12301 gtgggacttt gtaagegege tggagcaaaa cccaaatagc aagccgctca tggcgcagct 12361 gttccttata gtgcagcaca gcagggacaa cgaggcattc aggga gege tget aaa cat 12421 agtagagccc gagggeeget ggetgetega tttgataaac atcctgcaga gcatagtggt 12481 gcaggagcgc age gagee tggctgacaa ggtggccgcc atcaactatt ccatgcttag 12541 cctgggcaag ttttacgccc gcaagatata ccatacccct tacgttccca tagacaagga 12601 ggtaa agate gagggg tct acatgcgcat ggegetgaag g gc acc tgagegaega 12661 cctgggcgtt tatcgcaacg agcgcatcca caaggccgtg agegtgagee ggeggegega 12721 gc tcagcgac egegagetga tgcacagcc t gcaaagggcc ctggctggca cgggcagcgg 12781 egatagagag gccgagtcct aetttgaege gggcgctgac ctgcgctggg ccccaagccg 12841 acgcgccctg gaggcagctg gggccggacc tgggctggcg gtggcacccg cgcgcgctgg 12901 caacgtcggc ggcgtggagg aatatgaega ggaegatgag tacgagccag aggaeggega 12961 gtactaagcg gtgatgtttc tgatcagatg atgcaagacg caacggaccc ggeggtgegg 13021 gcggcgctgc agagccagcc gtc.c.ggcctt aactccacgg acgactggcg ccaggtcatg 13081 gaccgcatca tgtcgctgac tgcgcgcaat cctgacgcgt tccggcagca gccgcaggcc 13141 aaccggctct ccgcaattct ggaagcggtg gtc.c.c.ggc.gc gcgcaaaccc cacgcacgag 13201 aaggtgctgg c g t eg uaaa cgcgctggcc gaaaacaggg ccatccggcc cgacgaggcc 13261 ggcctggtct acgacgcgct gc.ttc.agcgc gtggctcgtt acaacagcgg caacgtgcag 13321 accaacctgg accggctggt gggggatgtg cgcgaggccg tggcgcagcg tgagcgcgcg 13381 cagcagcagg gcaacctggg ctccatgg gcactaaacg ccttcctgag a c a a ( i c c c 13441 gccaacgtgc cgcggggaca ggaggactac accaactttg tgagcgcact geggetaatg 13501 g gae aga caccgcaaag gagg g ac cagtctgggc cagactattt tttccagacc 13561 agtagacaag gcctgcagac cgt aaa cc g agccaggctt teaaaaaett gcaggggctg 13621 tggggggtgc gggctcccac aggcgaccgc gcgaccgtgt etagettget gacgcccaac 13681 tcgcgcctgt tgetgetget aatagcgccc ttcacggaca gtggcagcgt gtcccgggac 13741 acatacctag gtcac get gacactgtac cgcgaggcca agg eagge gcatgtggac 13801 gagcatactt tccaggagat tacaagtgtc agc.c.gc.gc.gc tggggcagga ggacacgggc 13861 ageetggagg caacccucicici ctacctgctg accaaccggc ggcagaagat cccctcgttg 13921 cacagtttaa acagcgagga ggagcgcatt ttgcgctacg tgcagcagag egtgageett 13981 aacc ga t qc gcgacggggt aacgcccagc gtggcgctgg acatgaccgc gcgcaacatg 14041 gaaccgggca tgtatgcctc aaaccggccg tttatc.aac.c gcctaatgga etaettgeat 14101 cgcgcggccg ccgtgaaccc egagtattte accaatgcca tcttgaaccc gcactggcta 14161 c.cgccccctg gtttctacac c.gggggattc gaggtgcccg agggtaaega tggattcctc 14221 tgggacgaca tagacgacag cgtgttttcc ccgcaaccgc agaccctgct agagttgcaa 14281 cagcgcgagc aggcagaggc ggegetgega aaggaaaget tccgcaggcc aagcagcttg 14341 teegatetag gcgctgcggc cccgcggtca gatgetagta gcccatttcc aagettgata 14401 gggtetetta ccagcactcg caccacccgc ccgcgcctgc gggcgagga ggagtaccta 14461 aacaactcgc tgctgcagcc gcagcgcgaa aaaaacctgc ctccggcatt u c c c a a c a a c 14521 ggga t a gaga gcctagtgga caagatgagt agatggaaga cgtacgcgca ggagc c gg 14581 gacgtgccag gcccgcgccc gcccacccgt egteaaagge acgaccgtca gcggggtctg 14641 gtgtgggagg a eg a tgactc ggc g cgac agcagcgtcc gga ttggg agggagtggc 14701 aacccgtttg cgcaccttcg ccccaggctg gggagaatgt rttaaaaaaa aaaaagcatg 14761 a tgcaaaata aaa actcac caaggcca g gcaccgagcg ttggttttct tgtattcccc 14821 ttagtatgcg gcgcgcggcg atgtatgagg aaggtcctcc tccctcctac gagagtgtgg 14881 tgagegegge gccag ggcg geggegetgg gttctccct cgatgctccc ctggacccgc14941 cgtttgtgcc tccgcggtac ctgcggccta ccggggggag aaacagcatc cgttactctg 15001 agt: tggcacc cctattcgac ac:cacccgt:g tgtacctggt ggacaacaag tcaacggatg 15061 tggcatccct gaactaccag aacgaccaca gcaactttct gaccacggtc attcaaaaca 15121 atgactacag cccgggggag gcaagcacac agaccatcaa tcttgacgac cggtcgcact 15181 ggggcggcga cctgaaaacc atcctgcata ccaacatgcc aaatgtgaac gagttcatgt 15241 ttaccaataa gtttaaggcg cgggtgatgg tgtcgcgctt gcctactaag gacaatcagg 15301 tggagctgaa atacgagtgg gtggagttca cgctgcccga gggcaactac tccgagacca 15361 tgaccataga ccttatgaac aacgcgatcg tggagcacta cttgaaagtg ggca acacia 15421 acggggttct ggaaagcgac atcggggtaa agtttgacac, ccgcaacttc agactggggt 15481 ttgaccccgt cactggtctt gtcatgcctg gggtatatac aaacgaagcc ttccatccag 15541 acatcatttt gctgccagga tgcggggtgg acttcaccca cagccgcctg agcaacttgt 15601 tgggcatccg caagcggcaa cccttccagg agggctttag gatcacctac gatgatctgg 15661 agggtggtaa c ttcxxr ca ctg ttgga tig tggacgcct cx:a gcgagc t: txjaaagatg 15721 acaccgaaca gggcgggggt ggcgcaggcg gcagcaacag cagtggcagc ggcgcggaag 15781 gaactccaa cgcggcagcc gcggc atgc a cxxjgtgga ggacatga c g tx:at cx:a 15841 ttcgcggcga cacctttgcc acacgggctg aggagaagcg cgctgaggcc gaagcagcgg 15901 ccgaagctgc cgcccccgct gcg c cccg aggtcgag gcx:tx:agaag aaaccggtga 15961 tcaaacccct gacagaggac agcaagaaac gcagttacaa cctaataagc aatgacagca 16021 ccttcaccca gtacxxjcagc tggtaccttg catacaacta cggcgaccct cagacx:ggaa 16081 tccgctcatg gaccctgctt tgcactcctg acgtaacctg cggctcggag caggtctact 16141 ggtcgttgcc agac tgat caagaccccg tgaccttccg ctxx:acgcgc cagatcagca 16201 actttccggt ggtgggcgcc gagctgttgc ccgtgcactc caagagcttc tacaacgacc 16261 aggccgtcta ctcccaactc atccgccagt tt a cctctct gacccacgtg ttcaatcgct 16321 ttcccgagaa ccagattttg gcgcgcccgc cagcccccac catcaccacc gtcagtgaaa 16381 acgttcctgc tctcac gat cacgggacgc taccgctgcg caacagcatc ggaggagtcc 16441 agcgagtgac cattactgac gccagacgcc gcacctgccc ctacgtttac aaggccctgg 16501 gcatagtctc gccgcgcgtc ctatcgagcc gcactttttg agcaagcatg tccatcctta 16561 tatcgcccag caataacaca ggctggggcc tgcgcttccc, aagcaagatg tttggcgggg 16621 ccaagaagcg ctccgaccaa cacccagtgc gcgtgcgcgg gcactaccgc gcgccctggg 16681 gcgcgcacaa acgcggccgc actgggcgca ccaccgtcga tgacgccatc gacgcggtgg 16741 tggaggaggc gcgcaactac acgcccacgc cgccaccagt gtccacagtg gacgcggcca 16801 tcagaccgt ggtgcgcgga gcccggcgc ti atgct aa t gaagagacgg cggaggcgcg 16861 tagcacgtcg ccaccgccgc cgacccggca ctgccgccca acgcgcggcg gcggccctgc 16921 tt accgcgc acgtxxjcacc ggccg cggg c gcx:atgcg ggccgctcga aggctggcxxj 16981 cgggtattgt cactgtgccc cccaggtcca ggcgacgagc ggccgccgca gcagccgcgg 17041 cca t tagtgc tatgactx:ag ggtcgcaggg gcaacgtgt ttgggtgcgc gactcggtta 17101 gcggcctgcg cgtgcccgtg cgcacccgcc ccccgcgcaa ctagattgca agaaaaaact 17161 acttagactc gtac t jOtgt atgtatccag c gcggcggc gcgcaacgaa gctatgtxx:a 17221 agcgcaaaat caaagaagag atgctccagg tcatcgcgcc, ggagatctat ggccccccga 17281 agaaggaaga gcaggattac aagccccgaa agctaaagcg ggtcaaaaag aaaaagaaag 17341 atgatgatga tgaacttgac gacgaggtgg aactgctgca cgctaccgcg cccaggcgac 17401 gggtacagtg gaaaggtcga cgcgtaaaac gtgttttgcg acccggcacc accgtagtct 17461 ttacgcccgg tgagcgctcc acccgcacct acaagcgcgt gtatgatgag gtgtacggcg 17521 acgaggacct gcttgagcag gccaacgagc gcctcgggga gtttgcctac ggaaagcggc 17581 ataaggacat gctggcgttg ccgctggacg agggcaaccc aacacctagc ctaaagcccg 17641 taacactgca gcaggtgctg cccgcgcttg caccgtccga agaaaagcgc ggcctaaagc 17701 gcgagtctgg tgacttggca cccaccgtgc agctgatggt acccaagcgc cagcgactgg 1 1761 aagatgtctt ggaaaaaatg accgtggaac ctgggctgga gcccgaggtc cgcgtgcggc 17821 caatcaagca ggtggcgccg ggactgggcg t cagacxxj t: ggacgttc g atacxx:acta 17881 ccagtagcac cagtattgcc accgccacag agggcatgga gacacaaacg tccccggttg 17941 cc tcagcggt ggcggatgcx: gcggtgcagg cggtcgctgc g cxxjcgtxx: aagacctcta 18001 cggaggtgca aacggacccg tggatgtttc gcgtttcagc cccccggcgc ccgcgccgtt 18061 cgaggaa ta cggcgccgcc agcgcgctac t cxxxjaata tgccctacat cx:ttxx:attg 18121 cgcctacccc cggctatcgt ggctacacct accgccccag aagacgagca actacccgac 18181 gccgaaccac cactgg acx: cgccgccgcc gtcgccgtcg cx:a cxxxjt c t jgccccga 18241 tttccgtgcg cagggtggct cgcgaaggag gcaggaccct ggtgctgcca acagcgcgct 18301 ccaccccag ca tx jt: t:taa aagccggtct ttgtggttx: t: tagcagatatg gcxx:tx:acx:t18361 gccgcctccg tttcccggtg ccgggattcc gaggaagaat gcaccgtagg aggggeatgg 18421 ccggccacgg cctgacgggc ggca gcgtc gtgcgcacc c egg egg egg cgcgcgtcgc 18481 accgtcgcat gcgcggcggt atcctgcccc tccttattcc actgatcgcc geggegattg 18541 gcgccgtgcc cggaattgca tccgtggcct tgcaggcgca gagacactga L L cl cl cl cl cl C o. o.18601 gttgcatgtg gaaaaatcaa aataaaaagt ctggactctc, acgctcgctt ggtcctgtaa 18661 ctattttgta gaatggaaga catcaacttt gcgtctctgg ccccgcgaca cggctcgcgc 18721 ccgttcatgg gaaactggca agatategge accagcaata tgagcggtgg cgccttcagc 18 81 tggggctcgc tgtggagcgg cattaaaaa ttcggttcca ccgttaagaa ctatggcagc 18841 aaggcctgga acagcagcac aggccagatg ctgagggata agttgaaaga gcaaaatttc 18901 caacaaaagg tggtagatgg cctggcctct ggcattagcg gggtggtgga cctggccaac 18961 caggcagtgc aaaataagat taacagtaag cttgatcccc gccctcccgt agaggagcct 19021 ccaccggccg tggagacagt gtctccagag gggcgtggcg aaaagcgtcc gcgccccgac 19081 agggaagaaa ctctggtgac gcaaa agac gagcctccct egtaegagga ggcac taaag 19141 caaggcctgc ccaccacccg tcccatcgcg cccatggcta ccggagtgct gggccagcac 19201 acacccg aa cgc ggacct gcctcccccc gccgacaccc agcagaaacc tgtgctgcca 19261 ggcccgaccg ccgttgttgt aacccgtcct agccgcgcgt ccctgcgccg cgccgccagc 19321 ggtccgcgat cgttgcggcc cgtagccagt ggcaactggc agcacac gaacagcatc 19381 gtgggtctgg gggtgcaatc cctgaagcgc cgacgatgct tetgataget aacgtgtcgt 19441 atgtgtgtca g a tgcgtc catgtcgccg ccagaggagc t get gage eg ccgcgcgccc 19501 gctttccaag atggctaccc ettegatgat gccgcagtgg tcttacatgc acatctcggg 19561 ccaggacgcc tcggagtacc tgagccccgg gctggtgc g tgcccgcg ccaccgagac 19621 gtacttcagc ctgaataaca agtttagaaa ccccacggtg gcgcctacgc acgacgtgac 19681 cacagaccgg tcccagcgtt tgacgctgcg gttcatccct gtggaccgtg aggataetge 19741 gtactcgtac aaggcgcggt tcaccctagc tgtgggtgat aaccgtgtgc tggacatggc 19801 ttccacgtac tttgacatcc geggegtget ggacaggggc cctactttta agccctactc 19861 tggcactgcc tacaacgccc tggctcccaa gggtgcccca aatccttgcg aatgggatga 19921 agctgctact gctcttgaaa taaacc uaga agaagaggac gatgacaacg aagaegaagt 19981 agacgagcaa gctgagcagc a a a a a a c u c a cgtatttggg caggcgcctt attetggtat 20041 aaatattaca aaggagggta ttcaaatagg tgtcgaaggt caaacaccta aatatgeega 20101 taaaacattt caacctgaac ctcaaatagg agaatctcag tggtacgaaa cagaaattaa 20161 tcatgcagct gggagagtcc taaaaaagac taccccaatg aaaccatgtt aeggtt c a t a 20221 tgcaaaaccc cl C cl cl cl (J ci ci ci a tg gag ggca aggcattctt g agcaac a a a a t g g a a a 20281 gctagaaagt caagtggaaa tgcaattttt ctcaactact gaggcagccg caggcaatgg 20341 gataac tg actcc taaag tggta gta cagtgaaga t: gtagatatag aaaccccaga 20401 cactcatatt tcttacatgc ccactattaa ggaaggtaac tcacgagaac taatgggcca 20461 acaa tctatg cccaacaggc ctaa aca t tgcttttagg gacaattt a t tggtetaat 20521 gtattacaac agcacgggta atatgggtgt tctggcgggc caagcatcgc agttgaatgc 20581 gttgtagat gcaagaca gaa c caga gctttca ac cagcttttgc ttgattccat 20641 tggtgataga accaggtact tttctatgtg gaatcaggct gttgacagct atgatccaga 20701 tgttagaatt attgaaaatc atggaactga agatgaactt ccaaattact gctttccact 20761 gggaggtgtg attaatacag agactcttac caaggtaaaa cctaaaacag gtcaggaaaa 20821 tgga uggga aaagatgcta cagaattttc agataaaaat gaaataagag eggaaa t dd 20881 ttttgccatg gaaatcaatc taaatgccaa cctgtggaga aatttcctgt actccaacat 20941 agcgctgtat ttgcccgaca agetaaagta cagtccttcc acgtaaaaa tttetgataa 21001 cccaaacacc tacgactaca tgaacaagcg agtggtggct cccgggctag tggaetgeta 21061 cattaacctt ggagcacgct ggtcccttga ctatatggac aacgtcaacc ca ettaacca 21121 ccaccgcaat gctggcctgc gctaccgctc aatgttgctg ggcaatggtc getatgtgee 21181 cttccacatc caggtgcctc agaagttett tgccattaaa aacctccttc tcctgccggg 21241 ctcatacacc acgagtgga act c ggaa ggatgttaac atggttctgc ag gc ccct 21301 aggaaatgac ctaagggttg acggagccag cattaagttt gatagcattt gcctttacgc 21361 cacc ttcttc ccc tggccc acaacaccgc ctccacgctt gaggccatgc t tagaaaega 21421 caccaacgac cagtccttta acgactatct ctccgccgcc aacatgctct accctatacc 21481 cgcc acgct accaacgtgc ccatatccat cccctcccgc aactgggcgg ct ccgcgg 21541 ctgggccttc acgcgcctta agactaagga aaccccatca ctgggctcgg gctacgaccc 21601 1 a c c c tactctggct ctataccc ta cctag tgga acc tttacc tcaaccacac 21661 ctttaagaag gtggccatta cctttgactc ttctgtcagc tggcctggca atgaccgcct 21721 gcttaccccc aacgagtttg aaattaagcg c cag tgac ggggaggg acaacg tgc21781 ccagtgtaac atgaccaaag actggttcct ggtacaaatg ctagctaact ataacattgg 21841 c tacc gggc ttc t cc cagagagc t c ggaccgc g actcct tc tttagaaa 21901 cttccagccc atgagccgtc aggtggtgga tgatactaaa tacaaggact accaacaggt 21961 gggcatccta caccaacaca acaactctgg atttgttggc taccttgccc ccaccatgcg 22021 cgaaggacag gcctaccctg ctaacttccc ctatccgctt ataggcaaga ccgcagttga 22081 cagcattacc cagaaaaagt ttctttgcga tcgcaccctt tggcgcatcc cattctccag 22141 taactttatg tccatgggcg cactcacaga cctgggccaa aaccttctct acgccaactc 22201 cgcccacgcg ctagacatga cttttgaggt ggatcccatg gacgagccca cccttcttt CL 22261 tgttttgttt gaagtctttg acgtggtccg tgtgcaccag ccgcaccgcg gcgtcatcga 22321 aaccgtgtac ctgcgcacgc ccttctcggc cggcaacgcc acaacataaa gaagcaagca 22381 acatcaacaa cagctgccgc catgggctcc agtgagcagg aactgaaagc cattgtcaaa 22441 gatcttggtt gtgggccata ttttttgggc acct a tgaca agcgctttcc aggctttgtt 22501 c tccacaca ge cgcctg cgcca agtc a cggccg gtcgcgagac tgggggcgt 22561 cactggatgg cctttgcctg gaacccgcac tcaaaaaca gctacctctt tgagcccttt 22621 ggct tc g accagcgact caagcaggtt taccagtttg agtacgagtc actcct cgc 22681 cgtagcgcca ttgcttcttc ccccgaccgc tgtataacgc tggaaaagtc cacccaaagc 22741 g tacaggggc ccaactcggc cgcctg tgga c t ctgc gca g t ct ccacgccttt 22801 gccaactggc cccaaactcc catggatcac aaccccacca tgaaccttat taccggggta 22861 cccaactcca tgctcaacag tcccc ggt cagcccaccc tgcg cgc a cc gaacag 22921 ctctacagct tcctggagcg ccactcgccc tacttccgca gccacagtgc gcagattagg 22981 agcgccac ctttttgtca ct gaaaaac atgtaaaaat aat ac a agacactttc 23041 aataaaggca aatgctttta tttgtacact ctcgggtgat atttacccc cacccttgcc 23101 gtctgcgccg tttaaaaatc aaaggggttc tgccgcgcat cgctatgcgc cactggcagg 23161 gacacgttgc gatactggtg tttagtgctc cacttaaact caggcacaac catccgcggc 23221 agctcggtga agttttcact ccacaggctg cgcaccatca ccaacgcgtt tagcaggtcg 23281 ggcgccgata tcttgaagtc gcagttgggg cctccgccct gcgcgcgcga gttgcgatac 23341 acagggttgc agcactggaa cactatcagc gccgggtggt gcacgctggc cagcacgctc 23401 ttgtcggaga tcagatccgc gtccaggtcc tccgcgttgc tcagggcgaa cggagtcaac 23461 tttggtagct gccttcccaa aaagggcgcg tgcccaggct ttgagttgca ctcgcaccgt 23521 agtggcatca aaaggtgacc gtgcccggtc tgggcgttag gatacagcgc ctgcataaaa 23581 gccttgatct gcttaaaagc cacctgagcc tttgcgcctt cagagaagaa C cl u Cj C C Cj C 8.8.23641 gac t: tgccgg aaa ctg tt ggccggacag gccgcg cg gcacgcagca cc ttgcgtcg 23701 gtgttggaga tctgcaccac atttcggccc caccggttct tcacgatctt ggccttgcta 23761 gactgctcct tcagcgcgcg ctgcccgttt tcgctcgtca catccatttc23821 tccttattta tcataatgct tccgtgtaga cacttaagct cgccttcgat ctcagcgcag 23881 cggtgcagcc acaacgcgca gcccg gggc cg g gc tagg cac c tctgcaaac 23941 gactgcaggt acgcctgcag gaatcgcccc atcatcgtca caaaggtctt gttgctggtg 24001 gg ca c gcaacccgcg gtgctcctcg cagccagg tcttgc c ggccgccaga 24061 gcttccactt ggtcaggcag tagtttgaag ttcgccttta gatcgttatc cacgtggtac 24121 ttgtccatca gcgcgcgcgc agcctccatg cccttctccc acgcagacac gatcggcaca 24181 ctcagcgggt tcatcaccgt aatttcactt tccgcttcgc tgggctcttc ctcttcctct 24241 tgcgtccgca taccacgcgc cactgggtcg tcttcattca gccgccgcac tgtgcgctta 24301 cctcctttgc catgcttgat tagcaccggt gggttgctga aacccaccat ttgtagcgcc 24361 acatcttctc tttcttcctc gctgtccacg attacctctg gtgatggcgg gcgctcgggc 24421 ttgggagaag ggcgcttctt tttcttcttg ggcgcaatgg ccaaatccgc cgccgaggtc 24481 gatggccgcg ggctgggtgt gcgcggcacc agcgcgtctt gtgatgagtc ttcctcgtcc 24541 tcggactcga tacgccgcct catccgcttt tttgggggcg cccggggagg cggcggcgac 24601 ggggacgggg acgacacgtc ctccatggtt gggggacgtc gcgccgcacc gcgtccgcgc 24661 tcgggggtgg tttcgcgctg ctcctcttcc cgactggcca t ccttc c ct taggcag 24721 aaaaagatca tggagtcagt cgagaagaag gacagcctaa ccgccccctc tgagttcgcc 24781 accaccgcct ccaccg t c cgccaacgcg cct ccacct ccccg cga ggc cccccg 24841 cttgaggagg aggaagtgat tatcgagcag gacccaggtt ttgtaagcga agacgacgag 24901 gaccgctcag taccaac ga gg t aag caagaccagg acaacgcaga ggcaaacgag 24961 gaacaagtcg ggcgggggga cgaaaggcat ggcgactacc tagatgtggg agacgacgtg 25021 c tgt tg gc atctgc c ccag gcgcc a ctgcg acgcg tgca agagcgc gc 25081 gatgtgcccc tcgccatagc ggatgtcagc cttgcctacg aacgccacct attctcaccg 25141 cgcg acccc ccaaacgcca agaaaacggc acatgcgagc ccaacccgcg cctcaacttc25201 taccccgtat ttgccgtgcc agaggtgctt gccacctatc acatcttttt ccaaaactgc 25261 aaga tacccc tatcctgccg qccaaccgc ageegagegg acaagcagct ggeettgegg 25321 cagggcgctg tcatacctga tatcgcctcg ctcaacgaag tgccaaaaat ctttgagggt 25381 cttggacgcg acgagaagcg cgcggcaaac gctctgcaac aggaaaacag egaaaatgaa 25441 agtcactctg gagtgttggt ggaactcgag ggtgacaacg cgcgcctagc cgtactaaaa 25501 cgcagcatcg aggtcaccca ctttgcctac ccggcactta acctaccccc caaggtcatg 25561 agcacagtca tgagtgagct gatc.gtgc.gc. cgtgcgcagc ccctggagag ggatgeaaat 25621 t cgcaagaac aaacagagga gggcctaccc gcagttggcg acgagcagct agegegetgg 25681 cttcaaacgc gcgagcctgc cgacttggag gagegaegea aactaatgat ggccgcagtg 25741 ctcgttaccg tggagcttga gtgcatgcag cggttctttg ctgacccgga gatgeagege 25801 aagctagagg aaacattgca ctacaccttt cgacagggct acgtacgcca ggeetgeaag 25861 atctccaacg tggagctctg caacctggtc tcct a ccttg gaattttgca cgaaaaccgc 25921 c t: tgggc a acgtgcttca ccacgc tc gggcg gg cgcgccgcga c tacgtccgc 25981 gactgcgttt acttatttct atgctacacc tggcagacgg ccatgggcgt ttggcagcag 26041 tgcttggagg agtgcaacct caaggagctg cagaaactgc taaagcaaaa ct aaggac 26101 ctatggacgg ccttcaacga gcgctccgtg gccgcgcacc tggcggacat cattttcccc 26161 gaacgcctgc tt accct gcaacagggt ctgcc g ct caccag ca aagc tgttg 26221 cagaacttta ggaactttat cctagagcgc teaggaatet tgcccgccac etgetgtgea 26281 cttcctagcg actt tgtgcc cattaagtac egegaa tgee ctccgccgc ttggggccac 26341 tgctaccttc tgcagctagc caactacctt gcctaccact ctgacataat ggaagacgtg 26401 agcggtg cg gtctactgga g g tcac tgt cgctgcaacc tatgcacccc gcaccgc cc 2646 ctggtttgca attcgcagct gc.ttaac.gaa agteaaatta tcggtacctt tgagctgcag 26521 ggtccctcgc ctgacgaaaa gtccgcggct ccggggttga aactcactcc ggggctgtgg 26581 acgtcggctt accttcgcaa atttgtacct gaggactacc, acgcccacga gattaggttc 26641 tacgaagacc aatcccgccc gcctaatgcg gagettaeeg cctgcgtcat tacccagggc 2670 cacattcttg gccaattgca agcc.atc.aac. aaagcccgcc aagagtttct getaegaaag 26761 ggacgggggg tttacttgga cccccagtcc ggegaggage tcaacccaat ccccccgccg 26821 ccgcagccct atcagcagca gccgcgggcc cttgcttccc aggatggcac CC Lclclclci S.3 26881 gctgcagctg ccgccgccac ccacggacga ggaggaatac cgggacaqtc aggcagagga 26941 ggttttggac gaggaggagg aggacatgat ggaagactgg gagagcctag aegaggaage 27001 ttccgaggtc gaagaggtgt cagacgaaac accgtcaccc tcggtcgcat tcccctcgcc 27061 ggcgcccc g aa tcggcaa ccggttccag c ggc c cctccgc tc c tc ggcgcc 27121 gccggcactg cccgttcgcc gacccaaccg tagatgggac accactggaa ccagggccgg 27181 t agtcc g cagccgccgc cgtt gccca agagcaacaa c gcgcc g gc cc c c 27241 tggcgcggg cacaagaacg ccatagttgc ttgcttgcaa gactgtgggg gcaacatctc 27301 c cgcccgc cgctttcttc tctacca te cggcg ggcc cccccg ta acatcctgca 27361 ttactaccgt catctctaca gcccatactg caccggcggc agcggcagca acagcagcgg 27421 ccacacag gcaaaggcga ccgg t gca a ac ctgac aaagcccaag aa ccacag 27481 cggcggcagc agcaggagga ggagcgctgc gtctggcgcc caacgaaccc gtatcgaccc 27541 gcgagcttag aaacaggatt tttcccactc tgtatgetat atttcaacag agcaggggcc 2760 aagaacaag i gctgaaaata aaaaacaggt ctctgcgatc cctcacccgc agetgeetgt 27661 a ucacaaaaa cgaagatcag cttcggcgca egetggaaga egeggagget ctcttcagta 27721 aatactgcgc gctgactctt aaggactagt ttcgcgccct ttctcaaatt taagegegaa 27781 aactacgtca tctccagcgg ccacacccgg cgccagcacc tgttgtcagc gccattatga 27841 gcaaggaaat tcccacgccc tacatgtgga gttaccagcc acaaatggga ettgeggetg 27901 gagctgccca agactactca acccgaauaa actacatgag cgcgggaccc cacatgatat 27961 cccgggtcaa cggaatacgc gcccaccgaa accgaattct cctggaacag geggetatta 28021 ccaccacacc tcgtaataac cttaatcccc gtagttggcc cgctgccctg gtgtaccagg 28081 agtcccgc tcccaccact gtggtacttc ccagagacgc ccaggccgaa g cag ga 28141 ctaactcagg ggcgcagctt gegggegget ttcgtcacag ggtgeggteg cccgggcagg 28201 g t taactca cctgacaatc agagggegag gt t cagc c acgacgag teggtg ge 28261 cctcgcttgg tctccgtccg gacgggacat ttcagatcgg cggcgccggc cgctcttcat 28321 tcacgcctcg tcaggca tc ctaactctgc a acc tegte ctctg gccg egete ggag 28381 gcattggaac tctgcaattt attgaggagt ttgtgccatc ggtctacttt aaccccttct 28441 cgggacctcc cggccactat ccgga tcaa t: tt t cctaa c gacgcg gtaaaggact 28501 cggcggacgg ctacgactga atgttaagtg gagaggcaga gcaactgcgc ctgaaacacc 28561 gg ccac g tcgccgccac aagtgctttg cccgcgactc cggtgagttt gc c g28621 d a L L^C C C Q o. ggatcatatc gagggcccgg cgcacggcgr ccggcttacc gcccagggag 28681 age t tgcceg agee ga egg ga a cccagcgccc cctgctagtt gagcgggaca 28741 ggggaccctg tgttctcact gtgatttgca actgtcctaa ccctggatta catcaagatc 28801 c uc uagtt dd tgteaggteg cctaagtcga ttaactagag tacccgggga tcttattccc 28861 tttaactaat aaaaaaaaa aataaagcat cacttactta aaatcagtta gcaaatttct 28921 gtccagttta ttcagcagca cctccttgcc ctcctcccag ctctggt 3 tt gcagcttcct 28981 cctggctgca aactttctcc O- a - c* -- a a a tggaatgtca gtttcctcct gttcctgtcc 29041 atccgcaccc actatcttca tgttgttgca gatgaagege gcaagaccgt c egaagatac 29101 cttcaacccc gtgtatccat atgacacgga aaccggtcct ccaactgtgc cttttcttac 29161 tcctcccttt gtatccccca atgggtttca agagagtccc cctggggtac tctctttgcg 29221 cctatccgaa cctctagtta cctccaatgg catgcttgcg ctcaaaatgg gcaacggcct 29281 c ucuctggac gaggeeggea accttacctc ccaaaatgta accactgtga gcccacctct 29341 c a a a a a a a c c aagtcaa ca taaacc tgga tatetgea cccctcacag t tacctcaga 29401 agccctaact gtggctgccg ccgcacctct aatggtcgcg ggcaacacac tcaccatgca 29461 a cac ggcc ccgc taaeeg tgcacgac c caaacttagc attgccaccc aaggacccct 29521 cacagtgtca gaaggaaagc tagccctgca aacatcaggc cccctcacca ccaccgatag 29581 c gt ccctt actatcactg cctcaccccc tctaactac gccactggta gc t gggcat 29641 tgacttgaaa gagcccattt atacacaaaa tggaaaacta ac t a. a. a. gt acggggctcc 29701 t tgcatgta acagacgacc taaacacttt g ccgtagca ac ggtccag gtgtgactat 29761 taataatact teettgeaaa ctaaagttac tggagccttg ggttttgatt C d C d d Cj' Cj' C d d 29821 t tge aett aatgtagcag gaggac taag g ttgatte C 3 C 3 CJ 3 C gee a act 29881 tgatgttagt tatccgtttg atgctcaaaa ccaactaaat ctaagactag gacagggccc 29941 tCLLittata aactcagccc acaacttgga tattaactac aacaaaggcc tttacttgtt 30001 tacagcttca aacaattcca aaaagcttga ggttaaccta agcactgcca aggggttgat 30061 gtttgacgct acagccatag ccattaatgc aggagatggg cttgaatttg gttcacctaa 30121 tgcaccaaac acaaatcccc t c a a a a e a a a aattggccat ggcctagaat ttgattcaaa 30181 caaggctatg gttcctaaac taggaaetgg cctt 3 gtttt gacagcacag gtgccattac 30241 agtaggaaac aaaaacaatg ataagctaac tttgtggacc, acaccagctc catctcctaa 30301 ctgtagacta aatgeagaga aagatgetaa actcactttg gtcttaacaa aatgtggcag 30361 teaaataett gctacagttt cagttttggc tgttaaaggc agtttggctc caatatctgg 30421 aacagtt c a a agtgctcatc ttattataag atttgacgaa aatggagtgc tactaaacaa 30481 tee tcctg gacccagaa attggaac t t gaaatgga gatettaetg aaggcacagc 30541 ctatacaaac gctgttggat ttatgcctaa cctatcagct tatcc 3 at ctcacggtaa 30601 aactgccaaa agta c g teagteaagt ttacttaaac ggagacaaaa ctaaacctgt 30661 aacactaacc attacactaa acggtacaca ggaaacagga gacacaactc caagtg c a t a 30721 c tc tatgtea ttttcatggg aetggte tgg ccacaactac attaatgaaa ta tttgccac 30781 atcctcttac actttttcat acattgccca agaataaaga atcgtttgtg ttatgtttca 30841 acgtgtttat ttttca g cagaaaattt caagtcatt t ttcattcagt ag t gccc 30901 caccaccaca tagcttatac agatcaccgt accttaatca aactcacaga accctagtat 30961 tcaacctgcc acctccctcc caacacacag agtacacagt cctttctccc cggctggcct 31021 taaaaagcat catatcatgg gtaacagaca tattettagg tgttatattc cacacggttt 31081 cctgtcgagc caaacgctca tcagtgatat taataaactc cccgggcagc teaettaagt 31141 teatgteget gtccagctgc tgagccacag gctgctgtcc, aacttgcggt tgettaaegg 31201 geggegaagg agaagtccac gcctacatgg gggtagagte ataategtge atcaggatag 31261 ggcggtggtg ctgcagcagc gegegaataa actgctgccg ccgccgctcc gteetgeagg 31321 aa Lacaacat ggcagtggtc tcctcagcga tgattcgcac cgcccgcagc ataaggegee 31381 ttgtcctccg ggcacagcag cgcaccctga tctcacttaa atcagcacag taaetgeage 31441 acagcaccac aatattgttc aaaatcccac agtgeaagge gctgtatcca aagctcatgg 31501 cggggaccac agaacccacg tggcca ca accacaagcg caggtagatt aagtggcgac 31561 ccctcataaa cacgctggac ataaacatta cctcttttgg catgttgtaa ttcaccacct 31621 cccggt cca tataaacctc tgattaaaca ggcgccatc caccaccatc c t acc age 31681 tggccaaaac ctgcccgccg gctatacact gcagggaacc gggactggaa caatgacagt 31741 ggagagccca ggac eg a ccatggatca teatgete t catgatatca atgttggcac 31801 a a c a c a g g c s. cacgtgcata cacttcctca ggattacaag ctcctcccgc gttagaacca 31861 cccaggg aacaacccat teetga tea gcgtaaatcc cacactgca ggaagacctc 31921 gcacgtaact cacgttgtgc attgteaaag tgttacattc gggcagcagc ggatgatcct 31981 ccag tggt agcgcggg tctgtc caa aaggaggtag acgatcccta etgtaeggag32041 tgcgccgaga caaccgagat cgtgttggtc gtagtgtcat gccaaatgga acgccggacg 32101 tagtcatatt tcctga ca aaaccaggtg c ggcgtg c aaacagatct gcgtctccgg 32161 tctcgccgct tagatcgctc tgtgtagtag ttgtagtata tccactctct caaagcatcc 32221 aggcgccccc tggcttcggg ttctatgtaa actccttcat gcgccgctgc cc u ataaca 32281 tccaccaccg cagaataagc cacacccagc caacctacac, attcgttctg cgagtcacac 32341 acgggaggag cgggaagagc tggaagaacc atgttttttt ttttattcca aaagattatc 32401 caaaacctca aaatgaagat ctattaagtg aacgcgctcc cctccggtgg cgtggtcaaa 32461 ctctacagcc aaagaacaga taatggcatt tgtaagatgt tgcacaatgg32521 gcaaacggcc ctcacgtcca agtggacgta aaggctaaac, ccttcagggt gaatctcctc 32581 tataaacatt ccagcacctt caaccatgcc caaataattc tcatctcgcc accttctcaa 32641 tatatctcta agcaaatccc gaatattaag tccggccatt gtaaaaatct gctccagagc 32701 gccctccacc ttcagcctca agcagcgaat catgattgca aaaattcagg ttcctcacag 32761 acctgtataa g ttca ag cggaaca t: ta acaaaaatac c c atcccg taggtccctt 32821 cgcagggcca gctgaacata atcgtgcagg tctgcacgga ccagcgcggc cacttccccg 32881 c c g g a a c c a gacaaaaga acccacactg a tatgacac gca tact egg agc atgcta 32941 accagcgtag ccccgatgta agcttgttgc atgggcggcg atataaaatg caaggtgctg 33001 c t c a a a a a a t caggcaaagc ctcgcgcaaa aaagaaagca catcgtag c a tgctcatgc 33061 agataaaggc aggtaagctc cggaaccacc Cd dSSSSg acaccatttt tctctcaaac 33121 a t g t c t g c g g gtt c tgcat aaacacaaaa a a a a a a c a taaaca tag 33181 aagcctgtct tacaacagga aaaacaaccc ttataagcat aagacggact acggccatgc 33241 cggcgtgacc gtaaaaaaac tgg caccgt gattaaaaag caccaccgac agctcctcgg 33301 tcatgtccgg agtcataatg taagactcgg taaacacatc aggttgattc actcggtcag 3 -i -i 6 tgciaaaaag cgaccgaaat agcccggggg aatacatacc egeaggegta gagacaacat 33421 tacagccccc ataggaggta taacaaaatt aataggagag aaaaacacat aaacacctga 33481 aaaaccctcc tgcctaggca aaatagcacc ctcccgctcc agaacaacat acagcgcttc 33541 cacagcggca gccataacag tcagccttac, cagtaaaaaa gaaaacctat3i 60 ccacucgaca cggcaccagc tcaatcagtc acagtgtaaa aaagggccaa gtgcagagcg 33661 agtatatata ggactaaaaa atgacgtaac ggttaaagtc cacaaaaaac acccagaaaa 33721 ccgcacgcga acctacgccc agaaacgaaa gccaaaaaac ccacaacttc ctcaaatcgt 33781 cacttccgtt ttcccacgtt acgtcacttc, ccattttaag a a a a c t a c a a ttcccaacac 33841 atacaagtta ctccgcccta aaacctacgt cacccgcccc gttcccacgc cccgcgccac 33901 gtcacaaact ccaccccctc atta ca ta t: t gcttca t ccaaaataag gtatattatt 33961 gatgatgSEQ ID NO: 22: rAd-EDll nucleotide sequence1 catcatcaat aatatacctt attttggatt gaagccaata tgataatgag ggggtggagt 61 ttgtgacgtg gcgcggggcg tgggaacggg gcgggtgacg tagtagtgtg gcggaagtgt 121 gatgttgcaa gtgtggcgga acacatgtaa gcgacggatg tggcaaaagt gacgtttttg 181 gtgtgcgccg gtgt cacag gaag gacaa ttttcgcgcg gttttaggcg gatgttgtag 241 taaatttggg cgtaaccgag taagatttgg ccattttcgc gggaaaactg aataagagga 301 agtgaaatct gaataatttt gtgttactca tagcgcgtaa tactGCTAGA gatCTGGCGA 361 AAGGGGGATG TGCTGCAAGG CGATTAAGTT GGGTAACGCC AGGGTTTTCC CAGTCACGAC 421 GTTGTAAAAC GACGGCCAGT GAATTGTAAT ACGACTCACT ATAGGGCGAA TTGGGTACTG 481 GCG CagGag cttggcccat tgcatacgtt gtatccatat cataatatgt acatttatat 541 tggctcatgt ccaacattac cgccatgttg acattgatta ttgactagtt attaatagta 601 atcaattacg gggtcattag ttcatagccc atatatggag ttccgcgtta cataacttac 661 ggtaaatggc ccgcctggct gaccgcccaa cgacccccgc ccattgacgt caataatgac 721 gtatgttccc atagtaacgc caatagggac tttccattga cgtcaatggg tggagtattt 781 acggtaaact gcccacttgg cagtacatca agtgtatcat atgccaagta cgccccctat 841 tgacgtcaat gacggtaaat ggcccgcctg gcattatgcc cagtacatga ccttatggga 901 ctttcctact tggcagtaca tctacgtatt agtcatcgct attaccatgg tgatgcggtt 961 ttggcagtac atcaatgggc gtggatagcg gtttgactca cggggatttc caagtctcca 1021 ccccattgac gtcaatggga gtttgttttg gcaccaaaat caacgggact ttccaaaatg 1081 tcgtaacaac tccgccccat tgacgcaaat gggcggtagg cgtgtacggt gggaggtcta1141 tataagcaga gctcgtttag tgaaccgtca gatcgcctgg agacgccatc cacgctgttt 1201 gacc cca agaagacacc gggaccga t:c cagcctgact ctagCctAGC TCtgaagttg 1261 gtggtgaggc cctgggcagg ttggtatcaa ggttacaaga caggttta.ag gagaccaata 1321 gaaactgggc atgtggagac agagaagact cttgggttt tgataggcac tgactctctc 1381 tgcctattgg tctattttcc cacccttagg ctgctggtc gagcctagGA GATCTCTCGA 1441 G GT C GAC GGT ATCGATGGGT ACCgccaccA TGAAGATGG TAGCAGCGAT GCCAATCCGA 1501 G GAT GGG TC CGCAGCCAAT CTGGTCCCGG AGGTTAACAA TGAAGTGATG GCTCTGGAAC 1561 CTGTGGTGGG TGCTGCAATC GCCGCACCTG T T GCAGGGC A GCAGAACGTT ATTGATCCCT 1621 GGATCAGGAA C c G T G CAAGCACCCG C AC C GT GA_Gc CCCAGGAACG 1681 CCCCAGGCGA AATTCTGTGG TCTGCCCCACTCTGAACCCC TAT CT GT CT C 1741 ACCTGGCAAG AATGTA AAC GGGTATGCCG GAGGGTTTGA GGTCCAGGTC ATCCTGGCGG 1801 GAAACGCCTT TACTGCAGGC AAGGTGATAT TTGCGGCCGT ACCTCCCAAT TTTCCAACCG 1861 AGGGACTTAG CCCATCCCAG GTGACAATGT TTCCTCACAT CGTGGTCGAT GTGCGCCAGC 1921 TTGAGCCAGT CCTGATTCCA CTGCCAGACG TGAGAAATAA CTTTTATCAT T AC AAT C AAT 1981 CAAACGACCC AACCATCAAA CTGATCGCCA TGCTGTACAC GCCAACAACG 2041 CTGGTGACGA GT GT CT T GT C GGGTCCTCAC TCGCCCCTCC CCAGATTTTG 2101 ACTTTATTTT TCTCGTGCCG CCAACGGTTG AAAGTAGGA AAAGCCTTTC TCCGTACCAG 2161 TGCTCACTGT GGAGGAGATG ACCAACAGCC GGTTTCCGAT CCCTCTGGAG AAACTGTTCA 2221 CGGGGCCTTC TAGTGCTTTC GTGGTTCAGC CACAAAACGC GAGGTGCACC AC AGAT GGC G 2281 TACTGCTTGG GACTACCCAG CTTAGCCCCG TGAATATTTG TACCTTCCGG GGGGATGTGA 2341 CACACATTAC CGGCTCCAGG AACTATACCA TGAATCTGG CTCCCAAAAT TGGAACGACT 2401 ATGATCCCAC CGAGGAGATC CCTGCCCCTC TGGGCACTC TGACTTTGTT GGAAAGATAC 2461 AGGGCGTCCT GACACAAACA ACAAGAACCG ATGGCTCTAC CCGGGGGCAT AAGGCAACCG 2521 TGTACACTGG GTCCGCTGAC TTTGCGCCCA AACTGGGACG GGTCCAATTC GAGACTGACA 2581 C AGAC C GAGA CTTCGAGGCG AAT CAGAACA CAAAGTTCA CCCTGTCGGT GTGATTCAGG 2641. AC G G G GG CAC CACTCATCGG AACGAGCCCC AACAGTGGG' CTTGCCCTCC TACTCCGGGA 2701 GGAATACTCA CAATGTTCAC CTGGCCCCCG CCGTGGCCCC CACGTTCCCA GGT GAACAAC 2761 TGCTGTTTTT TA. GA. T CT ACT1ATGCCTGGTT GTTCCGGCTA TCCAAACATG GACCTTGATT 2821 GTCTGCTGCC ACAGGAGTGG GTGCAGTATT TCTACCAGGA AGCAGCCCCA GCCCAGTCAG 2881 ATGTTGCCTT GCTTCGGTTC GTGAATCCTG GGTTCTCTTC G ATGCAAGC 2941 TGCACAAATC T GGC T C GT G ACGGTAGCGC ATACTGGACA GCATGACCTC GTCATTCCCC 3001 CAAACGGATA CTTTCGATTC GAT AGO T GGG TAAACCAGTT TTATACACTG GCACCTATGG 3061 GCAACGGGAC CGGCAGGAGG CGGGCGGTGT AACGATCGGA TATCGCTAGC GTACCGGCGG 3121 CCGCCCTATT CTATAGTGTC ACCTA A GC TAGAGCTCGC TGATCAGCCT C GA CT GT GC C 3181 TTCTAGTTGC CAGC CAT CT G TTGTTTGCCC CTCCCCCGTG CCTTCCTTGA CCCTGGAAGG 3241 TGCCACTCCC ACTGTCCTTT CCTAATAAAA TGAGGAAATT GCATCGCATT GTCTGAGTAG 3301 GTGTCATTCT ATTCTGGGGG GT GGGGT GGG GCA_GGA. CA. GC _AAGGGGGAGG ATTGGGAAGA 3361 CAA AGCAGG CATGCTGGGG ATGCGGTGGG CTCTATGGCT TCTGAGGCGG A A A G AC CAA 3421 AGCTTAcgcg ttagttatta ataGTAATCA CATTAGTTCA TAGCCCATAT 3481 ATGGAGTTCC GCGTTACATA ACTTACGGTA AATGGCCCG CTGGCTGACC GCCCAACGAC 3541 C C C C G C C CAT T GAC GT C AAT AATGACG AT TAACGCCAAT AGGGACTTTC 3601 CATTGACGTC AAT GGGT GGA GTATTTACGG TAAAC T GC C C ACTTGGCAGT ACATCAAGTG 3661 TATCATATGC CIAAGTA. CGCC CCCTATTGAC GTAAATGGCC CGCCTGGCAT 3721 TATGCCCAGT ACATGACCTT ATGGGACTTT CCTACTTGG AGTACATCTA CGTATTAGTC 3781 ATCGCTATTA CCATGGTGAT GCGGTTTTGGCAGT ACAT C A ATGGGCGTGG ATAGCGGTTT 3841 GACTCACGGG GAT T T C C AAG TCTCCACCCC ATTGACGTCA ATGGGAGTTT GTTTTGGCAC 3901 CAAAATCAAC GGGA. CTTTCC AAAATGTCGT AACAACTCCG CCCCATTGAC GCAAATGGGC 3961 GGTAGGCGTG TACGGTGGGA GGTCTATATA AGCAGAGCTG GTTTA. GTGAA CCGTCAGATC 4021 CGC AGAGAT a C c GGGC CAC T GC AGGAAAC GAT AT GGGC T GAATACGGAT CCGTATTCAG 4081 CCCATATCGT TTCTCTAGAA ATAAAATATC TTTATTTTCA TTACATCTGT GTGTTGGTTT 4141 TTTGTGTGaa tcgat gtac taacat cgc GAGCCTAAGC TTgtcgactc 4201 gaagatctgg gcgtggttaa gggtgggaaa aaatatataa ggtgggggtc ttatgtagtt 4261 ttgt tctgt tttgcagcag ccgccgccgc aactcgtttg tggaagcat 4321 tgtgagctca tatttgacaa cgcgcatgcc cccatgggcc ggggtgcgtc agaatgtgat 4381 gggc tccagc attgatggtc gccccg tec t: gcccgcaaac tctactacct tag cct a cga 4441 gaccgtgtct ggaacgccgt tggagactgc agcctccgcc gccgcttcag ccgctgcagc 4501 caccgcccqc ggga t: t: t a ctgactttgc ccgcttgcaa gcagtgcagc4561 ttcccgttca tccgcccgcg atgacaagtt gaeggetett ttggcacaat tggattcttt 462 gaccc ggaa ettaatgteg tttctcagca gctgttgg t c cgccagc gg c gc 4681 cctgaaggct tcctcccctc ccaatgcggt ttaaaacata a a t a a a a a a c cagactctgt 4741 ttggatttgg atcaagcaag tgtcttgctg tctttattta ggggttttgc gegegeggta 4801 ggcccgggac cagcggtctc ggtcgttgag ggtcctgtgt attttttcca ggacgtggta 4861 aaggtgactc tggatgttca gatacatggg cataagcccg tctctggggt ggaggtagca 4921 ccactgcaga gcttcatgct gcggggtggt gttgtagatg atccagtcgt ageaggageg 4981 ctgggcgtgg tgcctaaaaa tgtctttcag tagcaagctg attgccaggg gcaggccctt 5041 ggtgtaagtg tttacaaagc ggttaagctg ggatgggtgc atacgtgggg atatgagatg 5101 catcttggac tgtattttta ggttggctat gttcccagcc atatccctcc ggggattcat 5161 gttgtgcaga accaccagca cagtgtatcc, ggtgcacttg ggaaatttgt catgtagctt 5221 agaaggaaat gegtggaaga acttggagac gcccttgtga cctccaagat tttccatgca 5281 tcgtcc t tg tggcaa tgggcccacg g cggcggcc tgggcgaaga t c ggg 5341 atcactaacg tcatagttgt gttccaggat gagategtea taggccattt ttacaaagcg 5401 cgggcggagg gtgccagac gcggt t t g ttccatcc ggcccagggg cg agt acc 5461 ctcacagatt tgcatttccc acgctttgag ttcagatggg gggatcatgt ctacctgcgg 5521 ggcg g aaaacggttt ccgggg t: gg ggag tcagc tgggaagaaa gc cc 5581 gagcagctgc gacttaccgc agccggtggg cccgtaaatc acacctatta ccggCtgcaa 5641 ctggtagtta a ga gage gc agctgccgtc atccctgagc g gggcc ettegttaag 5701 catgtccctg actcgcatgt tttccctgac caaatccgcc agaaggeget cgccgcccag 5761 cga t c gt tettge a aagcaaagt t: tcaacggt tt agaccgt ccgcc gg 5821 catgcttttg agcgtttgac caagcagttc caggcggtcc cacagctcgg tcacctgctc 5881 tacggcatct cgatccagca tatctcctcg tttcgcgggt tggggcggct ttcgctgtac 5941 ggcagtagtc ggtgetegte cagacgggcc agggtcatgt ctttccacgg gcgcagggtc 6001 ctcgtcagcg tagtctgggt cacggtgaag gggtgcgctc cgggctgcgc gctggccagg 606 gtgcgcttga ggctggtcct gctggtgctg aagcgctgcc ggtcttcgcc ctgcgcgtcg 6121 gccaggtagc atttgaccat ggtgtcatag tccagcccct ccgcggcgtg gcccttggcg 6181 cgcagcttgc ccttggagga ggcgccgcac gaggggcagt gcagactttt gagggegtag 6241 agcttgggcg cgagaaatac cgattccggg gagtaggcat ccgcgccgca ggccccgcag 6301 acggtctcgc attccacgag ccaggtgagc tctggccgtt cggggtcaaa aaccaggttt 6361 cccccatgct ttttgatgcg tttcttacct ctggtttcca tgagccggtg tccacgctcg 6421 g tgac a a ggctgtcc t gtccccgta t: acagacttga gaggeetgte c e eggt 6481 gttccgcggt cctcctcgta tagaaactcg gaccactctg agacaaaggc tcgcgtccag 6541 gccagcacga aggagge a gtgggagggg tageggte t tccac g ggggtccact 6601 cgctccaggg tgtgaagaca catgtcgccc tcttcggcat caaggaaggt gattggtttg 6661 t ggt tagg ccacgtgacc gggtgt tec t: g ggggggc tataaaaggg gg gg gcg 6721 cgttcgtcct cactctcttc cgcatcgctg tetgegaggg ccagctgttg gggtgagtac 6781 tccctctgaa aagcgggc gacttctgcg ctaagatt t cagtttccaa aaaegaggag 6841 gatttgatat tcacctggcc cgcggtgatg cctttgaggg tggccgcatc catctggtca 6901 gaaaagacaa tctttttgtt gtcaagcttg gtggcaaacg acccgtagag ggcgttggac 696 agcaacttgg cgatggagcg cagggtttgg tttttgtcgc gateggegeg ctccttggcc 7021 gcga c gt 11 a getgeaegta ttcgcgcgca acgcaccgcc attcgggaaa gacggtggtg 7081 cgctcgtcgg gcaccaggtg cacgcgccaa ccgcggttgt gcagggtgac aaggtcaacg 7141 ctggtggcta cctctccgcg taggcgctcg ttggtccagc agaggeggee gcccttgcgc 7201 gagcagaatg gcggtagggg gtctagctgc, gtctcgtccg gggggtctgc gtccacggta 7261 aagaccccgg gcagcaggcg cgcgtcgaag tagtetatet tgcatccttg caagtctagc 7321 gcctgctgcc atgegeggge ggcaagcgcg egetegtatg ggttgagtgg gggaccccat 7381 ggcatggggt gggtgagege ggaggcgtac atgccgcaaa tgtcgtaaac gtagaggggc 7441 tctctgagta ttcc ag tgt gggt g catcttccac e egg ge ggcgcgcacg 7501 taatcgtata gttegtgega gggagcgagg aggtcgggac egaggttget acgggcgggc 7561 tgc tctgctc ggaagactat ctgcctgaag ggc tgtg agttggatga gga 7621 cgctggaaga cgttgaagct ggcgtctgtg agacctaccg cgtcacgcac gaaggaggcg 7681 t ggagtcgc gcagc t t g c cage teg gcggtgacc t gcacg c g ggcgcagtag 7741 tccagggttt ccttgatgat gteataetta tcctgtccct tttttttcca cagctcgcgg 7801 tgaggac a actcttcgcg gtctttccag tactcttgg tcggaaaccc g cggcctcc 7861 gaacggtaag agcctagcat gtagaactgg ttgacggcct ggtaggegea gcatcccttt 7921 tctacgggta gegegt ge c gcgcggcc ttccggagcg g gggt gagcgcaaag7981 gtgtccctga ccatgacttt gaggtactgg tatttgaagt cagtgtcgtc gcatccgccc 8041 tgctcccaga gcaaaaagtc cg gcgc t: t: t: ttgg cgcg gatt ggcag ggcgaagg g 8101 acatcgttga agagtatctt tcccgcgcga ggcataaagt tgcgtgtgat gcggaagggt 8161 cccggcacct cggaacggtt gttaattacc tgggcggcga gcacgatctc gteaaageeg 8221 ttgatgttgt ggcccacaat gtaaagttcc aagaagcgcg ggatgccctt gatggaaggc 8281 aattttttaa gttcctcgta ggtgagctct tcaggggagc tgagcccgtg ctctgaaagg 8341 gcccagtctg caagatgagg gttggaagcg acgaatgagc tccacaggtc acgggccatt 8401 agcaettgca ggtggtcgcg aaaggtccta aactggcgac ctatggccat tttttctggg 8461 gtgatgcagt agaaggtaag cgggtcttgt tcccagcggt cccatccaag gttegegget 8521 aggtctcgcg cggcagtcac tagaggctca tctccgccga aette CL tgac cagcatgaag 8581 ggcacgagct gcttcccaaa ggcccccatc caagtatagg ctctacatc gtaggtgaca 8641 aagagacgct cggtgcgagg atgcgagccg atcgggaaga actggatctc ccgccaccaa 8701 tggaggagt ggctattgat gtggtgaaag t ga gtccc tgcgacgggc cg cac cg 8761 tgctggcttt tgtaaaaacg tgcgcagtac tggcagcggt gcacgggctg tacatcctgc 8821 acgaggttga cc gacgacc gcgcac agg aagcagag g gga ttgag cccctcgcc 8881 ggcgggtttg gctggtggtc ttctacttcg gctgcttgtc cttgaccgtc tggetgeteg 8941 aggggagtta cggtgg tcg gaccaccacg ccgcgcg gc ccaaagtcca g tgtccgcg 9001 cgcggcggtc ggagcttgat gacaacatcg cgcagatggg agctgtccat ggtctggagc 9061 tcccgcggcg caggtc gg cgggagctcc tgcaggtt cc cgc g aegggteagg 9121 gcgcgggcta gatccaggtg atacctaatt tccaggggct ggttggtggc ggcgtcgatg 9181 gcttgcaaga ggccgc tcc ccgcggcgcg act cggt c cgcgcggcgg gcgg gggcc 9241 gcgggggtgt ccttggatga tgcatctaaa agcggtgacg cgggcgagcc cccggaggta 9301 gggggggctc cggacccgcc gggagagggg gcaggggcac gtcggcgccg cgcgcgggca 9361 ggagctggtg ctgcgcgcgt aggttgctgg cgaacgcgac, gaegeggegg ttgatctcct 9421 gaatctggcg cctctgcgtg aagacgacgg gcccggtgag cttgaAcctg aaagagagtt 9481 cgacagaatc aatttcggtg tcgttgacgg cggcctggcg caaaatctcc tgcacgtctc 9541 ctgagttgtc ttgataggcg atctcggcca tgaactgctc gatctcttcc i-cctggagat 9601 ctccgcgtcc ggctcgctcc acggtggcgg cgaggtcgtt ggaaatgegg gccatgagct 9661 gcgagaaggc gttgaggcct ccctcgttcc agacgcggct gtagaccacg cccccttcgg 9721 catcgcgggc gcgcatgacc acctgcgcga gattgagctc cacgtgccgg gegaagaegg 9781 cgtagtttcg caggcgctga aagaggtagt tgagggtggt ggcggtgtgt tctgccacga 9841 agaagtacat aacccagcgt cgcaacgtgg ttcgttg t tcccccaag gcc ca ggc 9901 gctccatggc ctcgtagaag tccacggcga agttgaaaaa ctgggagttg cgcgccgaca 9961 c g g 11 a a c t c ctcc tcc ga g cgg tga get eg gcga c agtgtcgcgc acctcgcgct 10021 caaaggctac aggggcctct tcttcttctt caatctcctc ttccataagg gcctcccctt 10081 cttcttcttc tggcggcggt gggggagggg ggac cggcg gcga eg a egg cgc ccggga 10141 ggcggtcgac aaagcgctcg atcatctccc cgcggcgacg gcgcatggtc teggtgaegg 10201 cgcggccgtt c cgcggggg cgc gttgga agacgccgcc cgtcatg cc cggttatggg 10261 ttggcggggg gctgccatgc ggcagggata cggcgctaac, gatgcatctc aacaattgtt 10321 gtgtaggtac tccgccgccg agggacctga gcgagtccgc atcgaccgga tcggaaaacc 10381 tctcgagaaa ggcgtctaac cagtcacagt egeaaggtag gctgagcacc gtggcgggcg 10441 gcagcgggcg gcggtcgggg ttgtttctgg eggaggtget getgatgatg caattaaagt 10501 aggcggtctt gagacggcgg atggtcgaca gaagcaccat gtccttgggt ccggcctgct 10561 gaatgcgcag gcggtcggcc atgccccagg cttcgttttg acatcggcgc aggtctttgt 10621 agtagtcttg catgagcctt tctaccggca cttcttcttc ccttcctct tgteetgeat 10681 ctcttgcatc tatcgctgcg gcggcggcgg agtttggccg taggtggege cctcttcctc 10741 ccatgcgtgt gaccccgaag cccctcatcg gctgaagcag ggetaggteg gcgacaacgc 10801 gctcggctaa tatggcctgc tgcacctgcg tgagggtaga etggaagtea tccatgtcca 10861 c a a a g c g g t g g a gcgccc gtgttgatgg tg aagtgea g ggcc a acggaccag 10921 taacggtctg gtgacccggc tgcgagagct cggtgtacct gagaegegag taagccctcg 10981 agtcaaatac gtagtcgttg caag ccgca cc gg c g gtatcccacc aa ag gcg 11041 gcggcggctg gcggtagagg ggccagcgta gggtggccgg ggctccgggg gegagatett 11101 c c a a c a t a a g gcga tg ccgt g tgt acctggaca t ccagg g g ccggcggcgg 11161 tggtggaggc gcgcggaaag tcgcggacgc ggttccagat gttgcgcagc ggcaaaaagt 11221 gctccatggt cgggacgctc tggccggtca ggcgcgcgc tcg tgacg c te aGegtg 11281 caaaaggaga gcctgtaagc gggcactctt ccgtggtctg g t g g a. t a. a. at tcgcaagggt 11341 a t c a t g g c g g acgaccgggg ttcgagcccc gta ccggcc g ccgccgtg atccatgcgg11401 ttaccgcccg cgtgtcgaac ccaggtgtgc gacgtcagac aacgggggag tgctcctttt 11461 ggc t: tcc c caggcgc gc ggc gc t:gcg c gcttttt gccac gg ccgcgcgcag 11521 cgtaagcggt taggctggaa agcgaaagca ttaagtggct cgctccctgt ageeggaggg 11581 ttattttcca agggttgagt cgcgggaccc ccggttcgag tctcggaccg gccggactgc 11641 ggcgaacggg ggtttgcctc cccgtcatgc aagaccccgc ttgeaaatte ctccggaaac 11701 agggacgagc cccttttttg cttttcccag atgcatccgg tgetgeggea gatgcgcccc 11761 cctcctcagc agcggcaaga gcaagagcag cggcagacat gcagggcacc ctcccctcct 11821 cctaccgcgt caggaggggc gacatccgcg gttgaegegg cagcagatgg egattaegaa 11881 cccccgcggc gccgggcccg gcactacctg gaettggagg agggcgaggg cctggcgcgg 11941 ctaggagcgc cctc i-cctga gcggCaccca agggtgeage tgaagcgtga taegegtgag 12001 gcgtacgtgc cgcggcagaa cctgtttcgc gaccgcgagg gagaggagee egaggagatg 12061 cgggatcgaa agttccacgc agggcgcgag ctgcggcatg geetgaateg cgagcggttg 12121 c tgcgc gg aggactttga gcccgacgcg cgaaccggga a cccgc gcgcgc cac 12181 gtggcggccg ccgacctggt aaccgcatac gagcagacgg tgaaccagga gattaaettt 12241 c aa aa ct ttaa caacca cgtgcgt cg cttgtggcgc geg ggaggt ggeta agga 12301 ctgatgcatc tgtgggactt tgtaagcgcg ctggagcaaa acccaaatag caagccgctc 12361 a tggc c gc tgttccttat ag gcagcac agcagggac egaggea tt caggg gcg 12421 ctgctaaaca tagtagagcc cgagggccgc tggetgeteg atttg a. t a. a a catcctgcag 12481 agcat gtgg gcagga c cage tt g ge etgge gac a ggeege catcaactat 12541 tccatgctta gcctgggcaa gttttacgcc egeaagatat accatacccc ttacgttccc 12601 a tagaca gg aggtaaagat cgaggggt tc tacatgcgca tggcgctgaa ggt c cc 12661 ttgagcgacg acctgggcgt ttatcgcaac gagcgcatcc acaaggccgt gagegtgage 12721 cggcggcgcg agctcagcga ccgcgagctg atgcacagcc tgcaaagggc cctggctggc 12781 acgggcagcg gcgatagaga ggccgagtcc tactttgacg cgggcgctga cctgcgctgg 12841 gccccaagcc gacgcgccct ggaggcagct ggggccggac ctgggctggc ggtggcaccc 12901 gcgcgcgctg gcaacgtcgg eggegtggag gaatatgacg aggaegatga gtacgagcca 12961 gaggacggcg agtactaagc ggtgatgttt ctgatcagat gatgcaagac ca<3C 8. CC 13021 cggcggtgcg ggcggcgctg cagagccagc cgtccggcct taactccacg gaegaetgge 13081 gccaggtcat ggaccgcatc atgtcgctga ctgcgcgcaa tcctgacgcg ttccggcagc 13141 agccgcaggc caaccggctc tccgcaattc tggaagcggt ggtcccggcg cgcgcaaacc 13201 ccacgcacga gaaggtgctg gegategtaa acgcgctggc cgaaaacagg gccatccggc 13261 cc gae gc cggcctg tc acgacgcgc c cagcg cgtggctcg tac ac gcg 13321 gcaacgtgca gaccaacctg gaccggctgg tgggggatgt gcgcgaggcc gtggcgcagc 13381 gtgagcgcgc gcagcagcag ggc acctgg gc cca tgg t tgcactaaac gcc cc ga 13441 gtacacagcc cgccaacgtg ccgcggggac aggaggacta caccaacttt gtgagcgcac 13501 gcggc aat ggtgactgag acaccgcaaa gagg g cca c ggg ccagactatt 13561 ttttccagac cagtagacaa ggeetgeaga ccgtaaacct gagccaggct ttcaaaaact 13621 tgcaggggct g ggggg cgggctccca caggcgaccg c cgaccg g te age ge 13681 tgacgcccaa ctcgcgcctg ttgctgctgc taatagegee cttcacggac agtggcagcg 13741 tgtcccggga cacataccta ggtcacttgc tgacactgta ccgcgaggcc ataggteagg 13801 cgcatgtgga cgagcatact ttccaggaga ttacaagtgt cagccgcgcg ctggggcagg 13861 aggacacggg cagcctggag gcaaccctaa actacctgct gaccaaccgg C gg C <3 <3 o. o.13921 tcccctcgtt gcacagttta aacagcgagg aggagcgcat tttgcgctac gtgcagcaga 13981 gcgtgagcct taacc i-gatg cgcgacgggg taacgcccag cgtggcgctg gacatgaccg 14041 cgcgcaacat ggaaccgggc atgtatgcct caaaccggcc gtttatcaac cgcctaatgg 14101 a c eacttgca tcgcgcggcc gccgtgaacc ccgagtattt caccaatgcc a ucttgaacc 14161 cgcactggct accgccccct ggtttctaca ccgggggatt cgaggtgccc gagggtaacg 14221 atggattcct ctgggacgac atagacgaca gcgtgttttc cccgcaaccg cagaccctgc 14281 t gagttgca acagcgc ag caggc gagg c gcgc gcg a aggaa gc ttccgcaggc 14341 caagcagctt gtccgatcta ggegetgegg ccccgcggtc agatgetagt agcccatttc 14401 caagc gggtctctt accagcac c gc cc cccg ccc cgcc g c tg gc gg 14461 aggagtacct aaacaactcg ctgctgcagc cgcagcgcga aaaaaacctg cctccggcat 14521 cccaacaa cggg tagag agcctagtgg acaaga tgag t gg g acg ac cgc 14581 aggagcdcsQ ggacgtgcca ggcccgcgcc cgcccacccg tegteaaagg cacgaccgtc 14641 agcgg g ct ggtgtgggag gaega tgac egge gaega c age a g eg c c tg gg 14701 gagggagtgg caacccgttt gcgcaccttc gccccaggct ggggagaatg ttttaaaaaa 14761 aa agca ga tgcaa aaaaaactca ccaaggcca t ggc ccg gc g g c14821 ttgtattccc ettagtatge ggcgcgcggc gatgtatgag gaaggtcctc ctccctccta 14881 cgagagtgtg gtgagegegg cgcca tggc ggcggcgctg ggttctccct tcg gctcc 14941 cctggacccg ccgtttgtgc ctccgcggta cctgcggcct accgggggga gaaacagcat 15001 ccgttactct gagttggcac ccctattcga caccacccgt gtgtacctgg LC^C^ciCciciCo. o.15061 gtcaacggat gtggcatccc tgaactacca gaacgaccac ageaaettte tgaccacggt 15121 cattcaaaac aatgactaca gcccggggga ggcaagcaca cagaccatca atettgaega 15181 ccggtcgcac tggggcggcg acctgaaaac catcctgcat accaacatgc caaatgtgaa 15241 cgagttcatg tttaccaata agtttaaggc gcgggtgatg gtgtcgcgct tgcctactaa 15301 ggacaatcag gtggagctga aatacgagtg ggtggagttc acgctgcccg agggcaacta 15361 ctccgagacc atgaccatag accttatgaa caacgcgatc gtggagcact aettgaaagt 15421 gggcagacag aacggggttc tggaaagega catcggggta aagtttgaca cccgcaactt 15481 cagactgg g tttgaccccg teaetggtet tgtcatgcct ggggtatata CSSclCCfclci C 15541 c t: tccatcca gac tx: ttt tgctgccagg tgcggggtg gacttcaccc acagccgcct 15601 gagcaacttg ttgggcatcc gcaagcggca acccttccag gagggcttta ggatcaccta 15661 cgatgatc g gagggtgg acattcccgc actgt gga t: gtgg cgcct accaggcgag 15721 cttgaaagat gacaccgaac agggcggggg tggcgcaggc ggcagcaaca gcagtggcag 15781 cggcgcgg gagaactcca acgcggcagc cgcggca tg c gccggtgg aggac tgaa 15841 cgatcatgcc attegeggeg acacctttgc cacacgggct gaggagaagc gegetgagge 15901 cgaagca cg geegaage g ccgcccccgc tgcgcaaccc g ggteg ga agcctcagaa 15961 gaaaccggtg atcaaacccc tgacagagga cagcaagaaa cgcagttaca acctaataag 16021 caa tgac gc accttcaccc ag accgcag ctggt cctt gcatacaact acggcg ccc 16081 tcagaccgga atccgctcat ggaccctgct ttgcactcct gacgtaacct geggetegga 16141 gcaggtctac tggtcgttgc cagacatgat gcaagacccc gtgaccttcc gctccacgcg 16201 ccagatcagc aactttccgg tggtgggcgc cgagctgttg cccgtgcact ccaagagctt 16261 ctacaacgac caggccgtct actcccaact catccgccag tttacctctc tgacccacgt 16321 gttcaatcgc tttcccgaga accagatttt ggcgcgcccg ccagccccca ccatcaccac 16381 eg i-ca gt gaa aacgttcctg ctctcacaga tcacgggacg ctaccgctgc gcaacagcat 16441 eggaggagte cagcgagtga ccattactga cgccagacgc, cgcacctgcc cctacgttta 16501 caaggccctg ggcatagtct cgccgcgcgt cctatcgagc cgcacttttt gagcaagcat 16561 gtccatcctt atatcgccca gcaataacac aggctggggc ctgcgcttcc caagcaagat 16621 gtttggcggg gccaagaagc gctccgacca acacccagtg cgcgtgcgcg ggcactaccg 16681 cgcgccctgg ggcgcgcaca aacgcggccg c ctgggcgc ccaccgtcg a tgacgcc t 16741 egaegeggtg gtggaggagg cgcgcaacta cacgcccacg ccgccaccag tgtccacagt 16801 ggacgcggcc a tcagaccg tggtgegegg a cccggcgc tatgetaaaa tg aga acg 16861 geggaggege gtagcacgtc gccaccgccg ccgacccggc actgccgccc aacgcgcggc 16921 ggcggccc g cttaaccgcg cacgtcgcac cggccgacgg gcggccatgc gggccgctcg 16981 aaggctggcc gcgggtattg tcactgtgcc ccccaggtcc aggegaegag cggccgccgc 17041 agcagccgcg gee a t: tagtg ct tgactc gggtcgcagg ggc cgtgt att ggtgcg 17101 cgactcggtt agcggcctgc gcgtgcccgt gcgcacccgc, cccccgcgca actagattgc 1 / 161 aagaaaaaac tacttagact cgtactgttg tatgtatcca geggeggegg cgcgcaacga 17221 agctatgtcc aagcgcaaaa tcaaagaaga gatgctccag gtcatcgcgc eggagateta 17281 tggccccccg aagaaggaag agcaggatta caagccccga aagetaaage gggtcaa o. o. o.17341 gaaaaagaaa gatgatgatg atgaaettga egaegaggtg gaaetgetge acgctaccgc 17401 gcccaggcga cgggtacagt ggaaaggteg aegegtaaaa cgtgttttgc gacccggcac 17461 caccgtagtc tttacgcccg gtgagcgctc cacccgcacc tacaagcgcg tgtatgatga 17521 ggtgtacggc gacgaggacc tgettgagea ggccaacgag cgcctcgggg agtttgccta 17581 eggaaagegg cataaggaca tgctggcgtt gccgctggac, gagggcaacc caacacctag 1 ‘7641 cctaaagccc gtaacactgc ageaggtget gcccgcgctt gcaccgtccg aagaaaagcg 17701 cggcct ag egegagte g gtgacttggc acccaccg g c gctg tgg t cxxxaagcg 17761 ccagcgactg gaagatgtet tggaaaaaat gaccgtggaa cctgggctgg agcccgaggt 17821 ccgcgtgcgg cca tx: gc agg tggc gee ggg ctgggc gtgeagaeeg tggacg tca 17881 gatacccact accagtagca ccagtattgc caccgccaca gagggcatgg agacacaaac 17941 g ccccg gcc cagcgg tggcgg tgc e egg geag geggtegetg cggccgcgtc 18001 caagacctct aeggaggtge aaacggaccc gtggatgttt cgcgtttcag ccccccggcg 18061 cccgcgcCgt teg gg t acggcgccgc c gcgcgct ctgcccgaa a tgccc ca 18121 tccttccatt gcgcctaccc ccggctatcg tggctacacc taccgcccca gaagaegage 18181 c cccga egee ga oca cc ctggaac CXXJCXXJCXXJC cgtcgccgtc gccagcccgt18241 gctggccccg atttccgtgc gcagggtggc tcgcgaagga ggcaggaccc tggtgctgcc 18301 a cagcgcgc taccacccca gca txxj t: t: tea a gccggtc tttgtggt tx: t: t jcagatat 18361 ggccctcacc tgccgcctcc gtttcccggt gccgggattc cgaggaagaa tgcaccgtag 18421 gaggggcatg gccggccacg gcctgacggg cggcatgcgt cgtgcgcacc accggcggcg 18481 gcgcgcgtcg caccgtcgca tgcgcggcgg tatcctgccc, ctccttattc cactgatcgc 18541 cgcggcgatt ggcgccgtgc ccggaattgc atccgtggcc ttgcaggcgc agagacactg 18601 cl C CelelclclclCc'i agttgcatgt ggaaaaatca aaataaaaag tctggactct cacgctcgct 18661 tggtcctgta actattttgt agaatggaag acatcaactt tgcgtctctg gccccgcgac 18721 acggctcgcg cccgttcatg ggaaactggc aagatatcgg caccagcaat atgagcggtg 18781 gcgccttcag ctggggctcg ctgtggagcg gcattaaaaa tttcggttcc accgttaaga 18841 actatggcag caaggcctgg aacagcagca caggccagat gctgagggat aagttgaaag 18901 agcaaaattt ccaacaaaag gtggtagatg gcctggcctc tggcattagc ggggtggtgg 18961 acc tcggccaa ccaggcagtg ca a a a t. a a a tt ac gt gcttga txxx: cgccctcccg 19021 tagaggagcc tccaccggcc gtggagacag tgtctccaga ggggcgtggc gaaaagcgtc 19081 cgcgccccga cagggaag actctggtga cgcaaataga cgagcctccc txrgtacgagg 19141 aggcacta 0.0. gcaaggcctg cccaccaccc gtcccatcgc gcccatggct accggagtgc 19201 gggccagca cacacccgta acgctggacc tgcctccccc cgccgacacc cagcagaaac 19261 ctgtgctgcc aggcccgacc gccgttgttg taacccgtcc tagccgcgcg tccctgcgcc 19321 gcgccgccag cggtxxxjcga tcgttgcggc ccgtagccag tggc actgg caaagcacac 19381 t g a a c a g c a. t cgtgggtctg ggggtgcaat ccctgaagcg ccgacgatgc ttctgatagc 19441 taacgtgtcg tatgtgtgtx: atgtatgcgt: ccatgtcgcc gccagaggag c txjctg gcc 19501 gccgcgcgcc cgctttccaa gatggctacc, ccttcgatga tgccgcagtg gtcttacatg 19561 cacatctcgg gccaggacgc ctcggagtac ctgagccccg ggctggtgca gtttgcccgc 19621 gccaccgaga cgtacttcag cctgaataac aagtttagaa accccacggt ggcgcctacg 19681 cacgacgtga ccacagaccg gtcccagcgt ttgacgctgc ggttcatccc tgtggaccgt 19741 gaggatactg cgtactcgta caaggcgcgg ttcaccctag ctgtgggtga taaccgtgtg 19801 ctggacatgg cttccacgta ctttgacatc cgcggcgtgc tggacagggg ccctactttt 19861 aagccctact ctggcactgc ctacaacgcc ctggctccca agggtgcccc aaatccttgc 19921 gaatgggatg aagctgctac tgctcttgaa ataaacctag <33 C 3 o. o. C[3 cgatgacaac 19981 gaagacgaag tagacgagca agctgagcag caaaaaactc acgtatttgg gcaggcgcct 20041 tattctggta taaatattac aaaggagggt attcaaatag gtgtcgaagg tcaaacacct 20101 aaa tea tgccg ataaaacatt tx:aacc t jaa cctcaaatag gagaa tx:tx:a gtxjgt cgaa 20161 acAgaaatta a t c a c g c a g c tgggagagtc ctAaaaaaga ctaccccaat gaaaccatgt 20221 t cggttcat atgcaaaacc cacaaatgaa aatggagggc aaggcattct tgtaaagcaa 20281 caaaatggaa agctagaaag tcaagtggaa atgcaatttt tctcaactac tgaggcAGcc 20341 gcaggcaatg gtg taactt gactxx: tea a a gtggt ttgt acagtgaaga t jtcagatata 20401 gaaaccccag acactcatat ttcttacatg cccactatta aggaaggtaa ctcacgagaa 20461 ct tgggcc a a c a a ■ c t a t gccca cagg cctaattaca ttgcttttag ggacaatttt 20521 attggtctaa tgtattacaa cagcacgggt aatatgggtg ttctggcggg ccaagcatcg 20581 cagttgaatg ctgttgtaga tttgcaagac agaaacacag agctttcata ccagcttttg 20641 cttgattcca ttggtgatag aaccaggtac, ttttctatgt ggaatcaggc tgttgacagc 20701 tatgatccag atgttagaat tattgaaaat catggaactg aagatgaact cccaaattac 20761 tgctttccac tgggaggtgt gattaataca gagactctta ccaaggtaaa acc taaaaca 20821 ggtcaggaaa atggatggga aaaagatgct acagaatttt cagataaaaa tgaaataaga 20881 gttggaaata attttgccat ggaaatcaat ctaaatgcca acctgtggag aaatttcctg 20941 t ac uc caa ca tagcgctgta tttgcccgac aagctaaagt acagtccttc caa cgt add 21001 atttctgata acccaaacac ctacgactac atgaacaagc, gagtggtggc tcccgggCta 21061 gtggactgct acattaacct tggagcacgc tggtcccttg actatatgga caacgtcaac 21121 ccatttaacc accaccgcaa tgctggcctg cgctaccgc t: c tgttgct gggcaatggt 21181 cgctatgtgc ccttccacat ccaggtgcct cagaagttct tgccattaa aaacctcctt 21241 c t:cc tcgccgg gctcatacac ctacgagtxjg aacttcagga aggatgttaa ca tcggttctg 21301 cagagctccc taggaaatga cctaagggtt gacggagcca gcattaagtt tgatagcatt 21361 tgcctttacg ccacc t: tcctt cccc tggcx: cacaacaccg cctccacgct tgaggccatg 21421 cttagaaacg acaccaacga ccagtccttt aacgactatc tctccgccgc caacatgctc 21481 taccctatac ccgccaacgc taccaacgtcg cccatatcca txxxxytxxxxj caactgggcg 21541 gctttccgcg gctgggcctt cacgcgcctt aagactaagg aaaccccatc actgggctcg 21601 ggct cgacc ctta t: tacac ctactctggc tx:tataccc t: acct g tgg aaccttttac21661 ctcaaccaca cctttaagaa ggtggccatt acctttgact cttctgtcag ctggcctggc 21721 a Ogaccgcc tgctt cccc caacgagt: t: t: gaaattaagc gctcagttga cgggg gggt 21781 tacaacgttg cccagtgtaa catgaccaaa gactggttcc tggtacaaat gctagctaac 21841 taTaacattq gctaccaggg cttctatatc ccagagagct acaaggaccg catgtactcc 21901 ttctttagaa acttccagcc catgagccgt caggtggtgg atgatactaa atacaaggac 21961 taccaacagg tgggcatcct acaccaacac aacaactctg gatttgttgg ctaccttgcc 22021 cccaccatgc gcgaaggaca ggcctaccct gctaacttcc cctatccgct tataggcaag 22081 accgcagttq acagcattac ccagaaaaag tttctttgcg atcgcaccct ttggcgcatc 22141 ccattctcca gtaactttat gtccatgggc gcactcacag acctgggcca aaaccttctc 22201 tacgccaact ccgcccacgc gctagacatg acttttgagg tggatcccat ggacgagccc 22261 acccttcttt atgttttgtt tgaagtcttt gacgtggtcc gtgtgcaccA gccgcaccgc ggcgtcatcg aaaccgtgta cctgcgcacg cccttctcgg ccggcaacgc cacaacat a 22381 agaagca gc a a c a c. a a c a acagctgccg cc tgggctc cagtgagcag gaactg ag 22441 ccattgtcaa agatcttggt tgtgggccat attttttggg cacctatgac aagcgctttc 22501 c ggctttgt ttctccacac aagctc cct gcgccatag t: c t cggcc ggtx:gcgaga 22561 ctgggggcgt acactggatg gcctttgcct ggaacccgca ctcaaaaaca tgctacctct 22621 Ogagccctt tggcttttct gaccagcgac tc agcaggt ttaccagttt gagt cgagt 22681 cactcctgcg ccgtagcgcc attgcttctt cccccgaccg ctgtataacg ctggaaaagt 22741 ccaccca ag cgtacagggg ccc actcgg ccgcctgtgg act ttctgc tgcatgtttx: 22801 tccacgcctt tgccaactgg ccccaaactc ccatggatca caaccccacc atgaacctta 22861 taccggggt acccaactcc atgctcaaca gtccccaggt acagcccacc c txjcgtcgca 22921 accaggaaca gctctacagc ttcctggagc, gccactcgcc ctacttccgc agccacagtg 22981 cgcagattaq gagcgccact tctttttgtc acttgaaaaa catgtaaaaa uaat tacta 23041 gagacacttt caataaaggc aaatgctttt atttgtacac, tctcgggtga ttatttaccc 23101 ccacccttgc cgtctgcgcc gtttaaaaat caaaggggtt ctgccgcgca tcgctatgcg 23161 ccactggcag ggacacgttg cgatactggt gtttagtgct ccacttaaac tcaggcacaa ccatccgcgg cagctcggtg aagttttcac tccacaggct gcgcaccatc accaacgcgt 23281 ttagcaggtc gggcgccgat atcttgaagt cgcagttggg gcctccgccc tgcgcgcgcg 23341 agttgcgata cacagggttg cagcactgga acactatcag cgccgggtgg tgcacgctgg 23401 ccagcacgct cttgtcggag atcagatccg cgtccaggtc ctccgcgttg ctcagggcga 23461 acggagt C o. o. ctttggtagc tgccttccca aaaagggcgc gtgcccaggc tttgagttgc 23521 c ticgcaccg tagtggcatc aaaagg t:gac cgtgcccggt ctgggcgtta ggat c gcg 23581 cctgcataaa agccttgatc tgcttaaaag ccacctgagc ctttgcgcct tcagagaaga 23641 acatgccgca agac t: t:gccg ga act t tggccggaca ggccgcgtcg tgcacgcagc 23701 accttgcgtc ggtgttggag atctgcacca catttcggcc ccaccggttc ttcacgatct 23761 tggccttgct agactgctcc ttcagcgcgc gctgcccgtt ttc ctcg c acatccattt 23821 caatcacgtg ctccttattt atcataatgc ttccgtgtag acacttaagc tcgccttcga 23881 tctcagcgca gcgg tgc gc cacaacgcgc a cccgtggg ctcgtg tgc ttgtaggtx:a 23941 cctctgcaaa cgactgcagg tacgcctgca ggaatcgccc catcatcgtc acaaaggtct 24001 tgttgctggt gaaggtcagc tgcaacccgc ggtgctcctc gttcagccag gtcttgcata 24061 cggccgccag agcttccact tggtcaggca gtagtttgaa gttcgccttt agatcgttat 24121 ccacgt ta cttgtccatc agcgcgcgcg cagcctccat gcccttctcc cacgcagaca 24181 cgatcggcac actcagcggg ttcatcaccg taatttcact ttccgcttcg ctgggctctt 24241 cctcttcctc ttgcgtccgc ataccacgcg ccactgggtc gtcttcattc agccgccgca 24301 ctgtgcgctt acctcctttg ccatgcttga ttagcaccgg tgggttgctg aaacccacca 24361 tttgtagcgc cacatcttct ctttcttcct cgctgtccac gattacctct ggtgatggcg 24421 ggcgctcggg cttgggagaa gggcgcttct ttttcttctt gggcgcaatg gccaaatccg 24481 ccgccgaggt cgatggccgc gggctgggtg tgcgcggcac cagcgcgtct tgtgatgagt 24541 cttcctcgtc ctxxjgactcg atacgccgcc tx:atxxxjct t: ttttgggggc gcccggggag 24601 gcggcggcga cggggacggg gacgacacgt cctccatggt tgggggacgt cgcgccgcac 24661 cgcglccgcg ctcgggggtg gtt txxjcgc t: gctcctcttc ccgactggcc a t: Otccttct 24721 cctataggca gaaaaagatc atggagtcag tcgagaagaa ggacagccta accgccccct 24781 ctgagttcgc caccaccgcc tcc cc t ccgccaacgc gcctaccacc ttxxxx: txxj 24841 aggcaccccc gcttgaggag gaggaagtga ttatcgagca ggacccaggt tttgtaagcg 24901 aagacg cga ggaccgctca gtaccaacag agg t aa gca gaccag gac acgcag 24961 aggcaaacga ggaacaagtc gggcgggggg acgaaaggca tggcgactac ctagatgtgg 25021 gagacgacgt gctg t: tgaag catctgcagc gccagtgcgc c tt tctgc gacgcgttgc25081 ci a a c o c o. cgatgtgccc ctcgccatag cggatgtcag ccttgcctac gaacgccacc 25141 t t: tctcacc gcgcgtaccc cccaaacgcc a ga aegg caca gcgag cccaacccgc 25201 gcctcaactt ctaccccgta tttgccgtgc cagaggtgct tgccacctat cacatctttt 25261 tccaaaactg caagataccc ctatcctgcc gtgccaaccg cagccgagcg gacaagcagc 25321 tggccttgcg gcagggcgct gtcatacctg atatcgcctc gctcaacgaa gtgccaaaaa 25381 tctttgaggg tettggaege gaegagaage gcgcggcaaa cgctctgcaa caggaaaaca 25441 gcgaaaatga aagtcactct ggagtgttgg tggaactcga gggtgacaac gcgcgcctag 25501 c eg eactaaa acgcagcatc gaggtcaccc actttgccta cccggcactt aacctacccc 25561 ccaaggtcat gagcacagtc atgagtgagc tgatcgtgcg ccgtgcgcag cccctggaga 25621 gggatgcaaa tttgcaagaa caaacagagg agggcctacc cgcagttggc gacgagcagc 25681 tagegegetg gcttcaaacg cgcgagcctg ccgacttgga ggagegaege aaactaatga 25741 tggccgcagt gctcgttacc gtggagcttg agtgeatgea gcggttcttt gctgacccgg 25801 aga tgcagcg caagctagag gaaaca t tgc actacacctt cgacagggc t cg cgcc 25861 aggeetgeaa gatctccaac gtggagctct gcaacctggt ctcctacctt ggaattttgc 25921 ega aaeeg cc gggcaa aaegtgette attccacgc t caagggcgag gcgcgccgcg 25981 actacgtccg egaetgegtt taettattte tatgctacac ctggcagacg gccatgggcg 26041 1: tggcagca g gc ggag gag gc a ace te aggaget gcagaaac g c taaagcaaa 26101 aettgaagga cctatggacg gccttcaacg agcgctccgt ggccgcgcac ctggcggaca 26161 tcattttccc cgaacgcc g ctt aaaccc t caacaggg tc gccagac ttcaccagtc 26221 aaagcatgtt gcagaacttt aggaaettta tcctagagcg ctcaggaatc ttgcccgcca 26281 cc tgctgtgc ac cc agc gac ttgtgc ccatt agt ccgcgaatgc cc tccgccgc 26341 tttggggcca ctgctacctt etgeagetag ccaactacct tgcctaccac tctgacataa 26401 tggaagacqt gagcggtgac ggtctactgg agtgtcactg tcgctgcaac ctatgcaccc 26461 cgcaccgctc cctggtttgc aattcgcagc tgettaaega aagteaaatt atcggtacct 26521 ttgagetgea gggtccctcg cctgacgaaa agtccgcggc tccggggttg aaactcactc 26581 cggggctgtg gaegtegget taccttcgca aatttgtacc tgaggactac cacgcccacg 26641 aga u uaggtt ctacgaagac caatcccgcc cgccTaatgc ggagcttacc gcctgcgtca 26701 ttacccaggg ccacattctt ggccaattgc aagccatcaa caaagcccgc caagagtttc 26 / 61 tgctacgaaa gggacggggg gtttacttgg acccccagtc eggegaggag ctcaacccaa 26821 tccccccgcc gccgcagccc tatcagcagc agccgcgggc ccttgcttcc caggatggca 26881 cccaaaaaga agetgeaget gccgccgcca cccacggacg aggaggaata ctgggacagt 26941 caggcagagg agg t ga egaggaggag g gg c tga gaagac g ggag gccta 27001 gaegaggaag cttccgaggt egaagaggtg teagaegaaa caccgtcacc ctcggtcgca 27061 ttcccctcgc cggcgcccca gaaateggea accggttcca gc ggc c aacctccgct 27121 cctcaggcgc cgccggcact gcccgttcgc cgacccaacc gtagatggga caccactgga 27181 accagggccg g g ccaa gcagccgccg ccgtt gccc agagcaaca acagcgccaa 27241 ggctaccgct catggcgcgg gcacaagaac gccatagttg ettgettgea agactgtggg 27301 ggcaacatct ccttcgcccg ccgct ctt ctctaccatc aeggeg gge cttcccccgt 27361 aacatcc.tgc attactaccg tcatctctac agcccatact gcaccggcgg cagcggcagc 27421 aacagcagcg ^CCHCclCclCfcl ageaaaggeg accggatagc aagactctga caaagcccaa 27481 gaaatccaca gcggcggcag cagcaggagg aggagegetg cgtctggcgc ccaacgaacc 27541 cgtatcgacc egegagetta gaaacaggat ttttcccact etgtatgeta ua ettcaaca 27601 gagcaggggc caagaacaag agetgaaaat aaaaaacagg tetetgegat ccctcacccg 2 / 661 cagctgcctg tatcacaaaa gegaagatea gcttcggcgc aegetggaag aegeggagge 27721 tctcttcagt aaatactgcg cgctgactct taaggactag tttcgcgccc tttctcaaat 27781 ttaagegega aaactacgtc atctccagcg gccacacccg gcgccagcac ctgtTgtcag 27841 cgccattatg agcaaggaaa ttcccacgcc ctacatgtgg agttaccagc cacaaatggg 27901 aettgegget ggagctgccc aagactactc aacccgaata aactacatga gcgcgggacc 27961 ccacatgata tcccgggtca acggaatAcg c cccaccga aaccgaattc tcCtggaaca 28021 ggeggetatt accaccacac ctcgtaataa ccttaatccc cgtagttggc ccgctgccct 28081 ggtgt ccag gaa gtcccg ctcccaccac tgtggt ctt cccagagacg ccc ggccga 28141 agttcagatg ac t a ac ucag gggcgcagct tgcgggcggc tttcgtcaca gggtgeggte 28201 gcccgggcag ggta taactc acc gaca cagagggcga gg c gc teaaegaega 28261 gteggtgage tcctcgcttg gtctccgtcc ggacgggaca tttcagatcg gcggcgccgg 28321 ccgCTcttca ttcacgcctc gtcaggcaa t cctaactctg cagacctcg cc tetgagee 28381 gegetetgga ggcattggaa ctctgcaatt tattgaggag tttgtgccat eggtetaett 28441 t accccttc tcgggacctc ccggccacta tccggatcaa tttattccta aetttgaege28501 ggtaaaggac tcggcggacg getaegaetg aatgttaagt ggagaggcag ageaaetgeg 28561 cc tg a c ctggtccact gtcgccgcca caagtgcttt gcccgcgact ccggtgagtt 28621 ttgctacttt gaattgcccg aggatcatat cgagggcccg gcgcacggcg tccggcttac 28681 cgccc ggqa gagcttgccc gtageetgat tcgggagttt acccagcgcc ccctgctagt 28741 tgagcgggac aggggaccct gtgttctcac tgtgatttgc aactgtccta accCtggatt 28801 acatcaagat cctc i-agtta ATGTCAGGTC GCC AAGTCG ATtaactaga gtacccgggg 28861 atcttattcc ctttaactaa t- o. o. a a a 515151 taataaagca teaett ett aaaatcagtt 28921 agcaaatttc tgtccagttt attcagcagc acctccttgc cctcctccca gc ectggtat 28981 tgcagcttcc tcctggctgc aaactttctc cacaatctaa atggaatgtc agtttcctcc 29041 tgttcctgtc catccgcacc cactatcttc atgttgttgc agatgaagcg cgcaagaccg 29101 tctgaagata ccttcaaccc cgtgtatcca tatgacacgg aaaccggtcc tccaactgtg 29161 ccttttctta ctcctccctt tgtatccccc aatgggtttc aagagagtcc ccctggggta 29221 c tc tctttgc gcctatccga acctctagt t: acctccaatg gcatgcttgc gc tcaaaatg 29281 ggcaacggcc tetetetgga cgaggccggc aaccttacct c cca aa t gt aaccactgtg 29341 gcccacctc t c a a a a a a a c caagtcaaac ataaacctgg aaat tctgc acccctcaca 29401 gttacctcag aagccctaac tgtggctgcc gccgcacctc taatggtege gggcaacaca 29461 c tcaccatgc aatcacaggc cccgctaacc gtgc cg ct ccaaacttag ca tt gee ace 29521 caaggacccc tcacagtgtc agaaggaaag ctagccctgc aaacatcagg ccccctcacc 29581 ccaccgata gcag taccct tactatcact gcctcacccc ctctaactac tgccactggt 29641 a g c g g g c a ttgacttgaa agagcccatt tatacacaaa atggaaaact aggactaaag 29701 tacggggctc ctttgc tgt aacagacgac ctaaacactt t accgtagc aactggtcca 29761 ggtgtgacta ttaataatac ttccttgcaa actaaagtta etggageett gggttttgat 29821 tcacaaggca atatgcaact taatgtagca ggaggactaa ggattgattc LC3333C3Q3 29881 cgccttatac ttgatgttag ttatccgttt gatgctcaaa accaactaaa tctaagacta 29941 ggacagggcc ctctttttat aaactcagcc cacaacttgg atattaacta caacaaaggc 30001 ctttacttgt ttacagcttc aaacaattcc aaaaagcttg aggttaacct aagcactgcc 30061 aaggggttga tgtttgacgc tacagccata gccattaatg caggagatgg gc etgaattt 30121 ggttcacc.ta atgcaccaaa cacaaatccc ctcaaaacaa aaattggcca tggcctagaa 30181 tttgattcaa acaaggctat ggttcctaaa etaggaaetg gccttagttt tgacagcaca 30241 ggtgccatta cagtaggaaa C 3.3.333 C 33 C gataagetaa ctttgtggac cacaccagct 30301 ccatctccta actgtagact aaatgeagag aaagatgeta aactcacttt ggtcttaaca 30361 aaa tgtggc gtcaaatact tgctacagt t: tcagttttgg ctgttaaagg cagtttggct 30421 ccaatatctg gaacagttca aagtgctcat ettattataa gatttgaega aaatggagtg 30481. a c a a a c a attcc t tcct gg ccc gaa tattggaac t ttagaaatgg g tcttact 30541 gaaggcacag cctatacaaa cgctgttgga tttatgccta acctatcagc ttatcca 3.3.3.30601 tc tea egg t aaactgccara aagtaaca t: t: gteagtea g tttacttaaa cggagacaaa 30661 actaaacctg taacactaac cattacacta aacggtacac aggaaacagg agacacaact 30721 ccaagtgcat a etc ta tgte attttcatgg gactggtctg gccacaacta cattaatgaa.30781 atatttgc.ca catcctctta cactttttca tac.attgc.c.c aagaataaag aatcgtttgt 30841 gttatgtttc aacgtgttta tttttcaatt gcagaaaatt teaagteatt tttcattcag 30901 tagtatagee ccaccaccac atagettata cagatcaccg tacctt tc aaactcacag 30961 a ccct gt ttcaacctgc cacctccctc ccaacacaca gagtacacag tcctttctcc 31021 ccggctggcc ttaaaaagca tcatatcatg ggtaacagac atattettag gtgttatatt 31081 ccacacggtt teetg cc gag ccaaacgctc atcagtgata a t aa t 333 ct ccccgggcag 31141 ctcacttaag ttcatgtcgc tgtccagctg ctgagccaca ggctgctgtc caacttgcgg 31201 ttgcttaacg ggeggegaag gagaagtcca cgcctacatg ggggtagagt cataatcgtg 31261 catcaggata gggcggtggt gctgcagcag egegegaata aactgctgcc gccgccgctc 31321 cgtcctgcag gaatacaaca tggcagtggt ctcctcagcg atgattegea ccgcccgcag 31381 cataaggcgc ettg tee tee gggcac gca gcgcaccctg atctcactta a tcagcaca 31441 gtaactgcag cacagcacca caatattgtt caaaatccca cagtgcaagg cgctgtatcc 31501 aaagctcatg gcggggacca cagaacccac gtggccatca taccacaagc gcaggtag t 31561 taagtggega cccctcataa acacgctgga cataaacatt acctcttttg gcatgttgta 31621 ttcaccacc tcccggtacc atataaacct ctgattaaac atggcgcc t cc ccaccat 31681 cctaaaccag ctggccaaaa cctgcccgcc ggctatacac tgcagggaac cgggactgga 31741 acaa tgacag tgg gagccc aggactcgta acc tgg tc tcatgctcg tcatgatatc 31801 aatgttggca caacacaggc acacgtgcat acacttcctc aggattacaa gctcctcccg 31861 cgtt aacc atatcccagg gaacaaccca ttcctgaatc agegtaaate cc cactgca31921 gggaagacct cgcacgtaac tcacgttgtg cattgtcaaa gtgttacatt cgggcagcag 3198 egg a ta atcc tccagtatgg tagcgcgggt: ttctgtctca aaaggaggta gac atccct 32041 actgtacgga gtgcgccgag acaaccgaga tcgtgttggt cgtagtgtca tgccaaatgg 32101 gtagtcatat ttcctgaagc aaaaccaggt gcgggcgtga ca acag tc 32161 tgcgtctccg gtctcgccgc ttagatcgct ctgtgtagta gttgtagtat atccactctc 32221 tcaaagcatc caggcgcccc ctggcttcgg gttctatgta aactccttca tgcgccgctg 32281 ccctgataac atccaccacc gcagaataag ccacacccag ccaacctaca cattcgttct 32341 gcgagtcaca cacgggagga gcgggaagag ctggaagaac catgtttttt tttttattcc 32401 aaaagattat ccaaaacctc aaaatgaaga tctattaagt gaacgcgctc ccctccggtg 32461 gcgtggtcaa actc uacagc caaagaacag ataatggcat i-t taagatg ttgcacaatg 32521 gcttccaaaa ggcaaacggc cctcacgtcc, aagtggacgt aaaggctaaa cccttcaggg 32581 tgaatctcct ctataaacat tccagcacct tcaaccatgc ccaaataatt ctcatctcgc 32641 cacc tatctca atatatctct aagcaaa tec cgaatattaa gtccggc:cat tagtaaaaaatc 32701 tgctccagag cgccctccac cttcagcctc aagcagcgaa tcatgattgc aaaaattcag 32761 gttcctcaca gacc tagtaata agattcaaaa gcggaacat t: aacaaaaata ccgcgatcxac 32821 gtaggtccct tcgcagggcc agctgaacat aatcgtgcag gtctgcacgg accagcgcgg 3288 ccac tatcccc gcc ggaacc Atgacaaaag gattatgaca cgcatactcg 32941 gagctatgct aaccagcgta gccccgatgt aagcttgttg catgggcggc gatataaaat 33001 gcaaggtgct gctcaaaaaa tcaggcaaag cctcgcgcaa aaaagaaagc ac tcgtagt 33061 catgctcatg cagataaagg caggtaagct ccggaaccac cacagaaaaa gacaccattt 3312 t t:c tctcaaa catgtctgcg ggtttc tagca taaac ca ataaaataac a a a a a a a c a t 33181 ttaaacatta gaagcctgtc ttacaacagg aaaaacaacc cttataagca taagacggac 33241 tacggccatg ccggcgtgac cgtaaaaaaa ctggtcaccg tgattaaaaa gcaccaccga 33301 cagctcctcg gtcatgtccg gagtcataat gtaagactcg gtaaacacat caggttgatt 33361 caCtcggtca gtgc i-aaaaa gcgaccgaaa tagcccgggg gaatacatac ccgcaggcgt 33421 agagacaaca ttacagcccc cataggaggt ataacaaaat taataggaga gaaaaacaca 33481 taaacacctg aaaaaccctc ctgcctaggc aaaatagcac cctcccgctc33541 tacagcgctt cCacagcggc agccAtaaca gtcagcctta ccagtaaaaa agaaaaccta 33601 ttaaaaaaac accactcgac acggcaccag ctcaatcagt cacagtgtaa aaaagggcca 33661 agtgcagagc gagtatatat aggactaaaa aatgacgtaa cggttaaagt ccacaaaaaa 337 z. i c a c c c a g a a a. accgcacgcg aacctacgcc cagaaacgaa aQ’CCcLcLcLcLQQ cccacaactt 33781 cctcaaatcg tcacttccgt tttcccacgt: tacgtCactt: cccattttaa gaaaactaca 33841 attcccaaca catacaagtt actccgccct aaaacctacg tcacccgccc cgttcccacg 33901 ccccgcgcca cgtcacaaac tccaccccct cattatcata ttggcttcaa tccaaaataa 33961 ggtatattat tgatgatgSEQ ID NO: 23: rAd-WS23 nucleotide sequence1 catcatcaat aatatacctt attttggatt gaagccaata gataatgag ggggtggagt 61 ttgtgacgtg gcgcggggcg tgggaacggg gcgggtg cg t: a g t a g t g t g g c g g a a g t g t 121 gatgttgcaa gtgtggcgga acacatgtaa gcgacggatg tggcaaaagt gacgtttttg 181 gtgtgcgccg gtgtacacag gaagtgacaa ttttcgcgcg g t: 111 a g g c g g a t: g 11 g t a g 241 taaatttggg cgtaaccgag taagatttgg ccattttcgc gggaaaactg aataagagga 301 agtgaaatct gaataatttt gtgttactca tagcgcgtaa t: a c t g c t a g a g a t: c t g g c g a 361 aagggggatg tgctgcaagg cgattaagtt gggtaacgcc agggttttcc cagtcacgac 421 g 11: g t: a a a a c g a c g g c c a g t g a a 11 g t a a t: a c g a c t c a c t a t: a g g g c g a a 11: g g g t a c t g 481 gccacaggag cttggcccat tgcatacgtt gtatccatat cataatatgt acatttatat 541 tggctcatgt ccaacattac cgccatgttg acattgatta ttgactagtt attaatagta 601 atcaattacg gggtcattag ttcatagccc, atatatggag ttccgcgtta cataacttac 661 ggtaaatggc ccgcctggct gaccgcccaa cgacccccgc ccattgacgt caataatgac 721 gtatgttccc atagtaacgc caatagggac tttccattga cgtcaatggg tggagtattt 781 acggtaaact gcccacttgg cagtacatca agtgtatcat atgccaagta cgccccctat 841 tgacgtcaat gacggtaaat ggcccgcctg gcattatgcc cagtacatga ccttatggga 901 ctttcctact tggcagtaca tctacgtatt agtcatcgct attaccatgg tgatgcggtt 961 ttggcagtac atcaatgggc gtggatagcg gtttgactca cggggatttc caagtctcca1021 ccccattgac gtcaatggga gtttgttttg gcaccaaaat caacgggact ttccaaaatg 1081 tcgtaacaac tccgccccat tgacgcaaa t gggeggt gg cgt tacggt ggg g eta 1141 tataagcaga gctctcccta tcagtgatag agatctccct atcagtgata gagategteg 1201 acgagctcgt ttagtgaacc gteagatege etggagaege catccacgct gttttgacct 1261 ccatagaaga caccgggacc gatccagcct ccgggtacca ccggtcttaa gatttccacc 1321 atgatgatgg cctcaaagga cgccacaagc tctgtggatg gcgcctctgg cgccggccag 1381 ctcgtgcctg aggtgaaege cagcgaccct ctggccatgg accccgtggc cggctccagc 1441 accgccgtgg ccaccgccgg ccaagtgaac cccatcgacc cctggatcat caacaacttc 1501 gtgcaggcac cccagggcga gttcaccatc agccctaaca acacccctgg agatgtgctg 1561 ttcgacctgt ctctgggacc tcacctgaac cctttcctgc tgcacctgtc tcagatgtac 1621 aacggctggg tgggcaacat gegtgtgaga atcatgctgg ctggaaatgc cttcacagct 1681 ggcaagatca tegtgagetg catccctcct ggetteggea gccataatct gaccattgcc 1741 caggc c c tgttccccca eg t gat egee gatgtgegga ccctggatcc a tegaggtg 1801 cccctggaag atgtgcggaa cgtgctgttt cacaacaacg & C 8. o. o. o. C C S gcagaccatg 1861 agac gtgt gcatgc t ta caccccactc agaaccggcg gaggaaccgg cgacagcttc 1921 gtggtggctg gcagagtgat gacctgtcct agccccgact tcaacttcct gtttctggtt 1981 cc tcc ccg tgg c aa gaccagaccc taccctgc ctaatctgcc tc tgagttct 2041 ctgagcaaca gcagagcccc cctgcctatt tccagcatgg gcatctcccc egataaegtg 2101 cagagcgtgc a a 111 c a g cggcagg gt accctcgacg gcagactggt cggaacaacc 2161 cccgtgagcc tgagccacgt ggccaagatc cggggcacat ccaacggcac agttat c a a t c tgacc gc tgg cggcac ccctttccac cctttcgagg gccctgcccc ta teggettt 2281 cctgacctgg ggggctgcga ctggcacatc, aacatgaccc agttcggcca cagcagccag 2341 acacaatacg acgtggacac cacccctgat accttcgtgc cacatctggg cagcatccag 2401 gccaacggga tcggcagcgg caattacgtg ggagtgctga gctggatcag ccctccaagc 2461 caccccagcg gaagccaggt ggacctgtgg aagattccta actacggctc tagcatcacc 2521 gaggccacac acctggcccc tagcgtgtac, cctccaggct teggegaagt cctggtcttc 2581 t i.ca gagca aaatgcccgg ccccggagcc tacaatctgc cctgcctgct acctcaggag 2641 tacatctctc acctggcctc cgagcaagct cctacagtgg gagaageege cctgctgcac 2701 tacgtggacc ctgacacagg ccggaacctg ggegaattea aggcctatcc tgatggattt 2761 ctgacatgcg tgcctaacgg cgctagctcc, ggccctcagc agctgcctat caacggcgtg 2821 ttcgtgttcg tctcctgggt cagcagattc taccagctta aacctgtggg caccgcttct 2881 agcgccagag gccgcctcgg cctgcggaga teg te ggctagcgta ccggcggccg 2941 ccctattcta tagtgtcacc taaatgetag agetegetga tcagcctcga ctgtgccttc 3001 tagttgccag ccatc tg g tttgcccctc ccccgtgcc t tcc tgaccc tggaag tgc 3061 cactcccact gtcctttcct aataaaa g a ggaaattgea tcgcattgtc tgagtaggtg 3121 ea e t ctggggg t gggtggggc ggac gca g ggggaggatt gggaag caa 3181 tagcaggcat gctggggatg cggtgggctc tatggettet gaggeggaaa gaaccaaagc 3241 ttacgcgtta gtta t ta gc gatetgeate teaattagte agcaaccata gtcccgcccc 3301 taactccgcc catcccgccc ctaactccgc ccagttccgc, ccattctccg ccccatcgct 3361 gactaatttt ttttatttat gcagaggccg aggccgcctc ggcctctgag ctattccaga 3421 agtagtgagg aggctttttt ggaggcctag gcttttgcga teegetagag atatcgggaa 3481 aega eatggg etgaataegg atccgtattc agcccatatc gtttctctag aaa t aaa ata 3541 tctttatttt cattacatct gtgtgttggt tttttgtgtg aategatagt actaacatac 3601 gctctccatc tcgagcctaa gcttgtcgac tegaagatet gggcgtggtt aagggtggga 3661 aagaatatat aaggtggggg tettatgtag ttttgtatct gttttgcagc agccgccgcc 3721 J C C cl L cl C ci ccaactcgtt tgatggaagc attgtgaget catatttgac aacgcgcatg 3781 cccccatggg ccggggtgcg tcagaatgtg atgggctcca gcattgatgg tcgccccgtc 3841 ctgcccgcaa actctactac cttgacctac gagaccgtgt ctggaacgcc gttggagact 3901 gcagcctccg ccgccgc c gccgc gc gccaccgccc gcggg ttgt gaetgaettt 3961 gctttcctga gcccgcttgc aagcagtgca gcttcccgtt catccgcccg c g a t g a c a. a. g 4021 tgac gctc ttttggcaca attgga t tc t gacccggg aacttaatgt cgt c cag 4081 cagctgttgg atctgcgcca gcaggtttct gccctgaagg cttcctcccc tcccaatgcg 4141 Cf l ci ci ci C ci La a a e a a accagactct gtttggatt t gg caagca ag tcttgc 4201 tgtctttatt taggggtttt gcgcgcgcgg taggcccggg accagcggtc tcggtcgttg 4261 aggg cc gt gtat t ttc caggacgtgg aggtg c ctggatgtt cag acatg 4321 ggcataagcc cgtctctggg gtggaggtag caccactgca gagcttcatg ctgcggggtg 4381 gtgt taga tgatccagtc gtagcaggag cgctgggcg t g cct a aa tctttc4441 agtagcaagc tgattgccag gggcaggccc ttggtgtaag gtttacaaa gcggttaagc 450 tggga tgggt gc t cgt g gga tat gaga tgcatcttgg act tatttt t gg ggct 4561 atgttcccag ccatatccct ccggggattc atgttgtgca gaaccaccag cacagtgtat 4621 ccggtgcact tgggaaattt gtcatgtagc ttagaaggaa atgcgtggaa gaacttggag 4681 acgcccttgt gacctccaag attttccatg cattcgtcca taatgatggc aatgggccca 4741 cgggcggcgg cctgggcgaa gatatttctg ggatcactaa cgtcatagtt gtgttccagg 4801 atgagatcgt cataggccat ttttacaaag cgcgggcgga gggtgccaga ctgcggtata 4861 atggttccat ccggcccagg ggcgtagtta ccctcacaga tttgcatttc ccacgctttg 4921 agttcagatg gggggatcat gtctacctgc ggggcgatga agaaaacggt ttccggggta 4981 ggggagatca gctgggaaga aagcaggttc ctgagcagct gcgacttacc gcagccggtg 5041 ggcccgtaaa tcacacctat taccggctgc aactggtagt taagagagct gcagctgccg 5101 tcatccctga gcaggggggc cacttcgtta agcatgtccc tgactcgcat gttttccctg 5161 accaaatccg ccagaaggcg ctcgccgccc agcg t gc gttcttgcaa gg gc ag 5221 tttttcaacg gtttgagacc gtccgccgta ggcatgcttt tgagcgtttg accaagcagt 5281 tccaggc gt cccacagctc ggtcacc gc tctacggca t: c cg tcc g ca atctcct 5341 cgtttcgcgg gttggggcgg ctttcgctgt acggcagtag tcggtgctcg tccagacggg 5401 ccagggtcat gtctttccac gggcgcaggg tcctcgtcag cgtagtctgg gtcacggtga 5461 aggggtgcgc tccgggctgc gcgctggcca gggtgcgctt gaggctggtc ctgctggtgc 5521 tgaagcgctg cxxjg tc t cg ccctgcgcgt e g ex: a ggta gc tttgacc atggtgtcat 5581 agtccagccc ctccgcggcg tggcccttgg cgcgcagctt gcccttggag gaggcgccgc 5641 acgaggggc gtgc gactt ttgagggcgt agagcttggg cgcgagaaat accg ccg 5701 gggagtaggc atccgcgccg caggccccgc agacggtctc gcattccacg agccaggtga 5761 gctctggccg ttcggggtca aaaaccaggt ttcccccatg ctttttgatg cgtttcttac 5821 ctctggtttc catgagccgg tgtccacgct cggtgacgaa aaggctgtcc gtgtccccgt 5881 atacagactt gagaggcctg tcctcgagcg gtgttccgcg gtcctcctcg tatagaaact 5941 cggaccactc tgagacaaag gctcgcgtcc aggccagcac gaaggaggct aagtgggagg 6001 ggtagcggtc gttgtccact agggggtcca ctcgctccag ggtgtgaaga cacatgtcgc 6061 cctcttcggc atcaaggaag gtgattggtt tgtaggtgta ggccacgtga ccgggtgttc 6121 ctgaaggggg gc t a uaaaag ggggtggggg cgcgttcgtc ctcactctct tccgcatcgc 6181 tgtctgcgag ggccagctgt tggggtgagt actccctctg aaaagcgggc atgacttctg 6241 cgctaagatt gtcagtttcc aaaaacgagg aggatttgat attcacctgg cccgcggtga 6301 tgcc t gag ggtggcc ca tccatc tggt cagaaaagac aatctttttg t: tg caagct 6361 tggtggcaaa cgacccgtag agggcgttgg acagcaactt ggcgatggag cgcagggttt 6421 ggtt tt tc gcga tcggcg cgctcc gg ccgcgatgt t: t gctgc cg ta tcgcgcg 6481 caacgcaccg ccattcggga aagacggtgg tgcgctcgtc gggcaccagg tgcacgcgcc 6541 a ccgcggtt gtgc gg t acaagg tea a cgctggtggc acctctccg cgt ggcgct 6601 cgttggtcca gcagaggcgg ccgcccttgc gcgagcagaa tggcggtagg gggtctagct 6661 gcg ctc tc cggggggtct gcgtcc cgg taaagacccc gggc gc gg cgcgcgtcga 6721 agtagtctat cttgcatcct tgeaagteta gcgcctgctg ccatgcgcgg gcggcaagcg 6781 cgcgctcgta tgggttgagt gggggacccc atggcatggg gtgggtgagc gcggaggcgt 6841 acatgccgca aatgtcgtaa aegtagaggg gctctctgag tattccaaga tatgtagggt 6901 agcatcttcc accgcggatg ctggcgcgca cgtaatcgta tagttcgtgc Cj cl Cj cl C ci 6961 ggaggtcggg accgaggttg etaegggegg gctgctctgc, tcggaagact atctgcctga 7021 agatggcatg tgagttggat gatatggttg gacgctggaa gacgttgaag ctggcgtctg 7081 tgagacctac cgcgtcacgc aegaaggagg cgtaggagtc gcgcagcttg ttgaccagct 7141 cggcggtgac ctgcacgtct agggcgcagt agtccagggt ttccttgatg atgtcatact 7201 tatcctgtcc cttttttttc cacagctcgc ggttgaggac aaactcttcg cggtctttcc ‘7261 agtactcttg gatcggaaac ccgtcggcct ccgaacggta agagcctagc atgtagaact 7321 ggttgac gc ctgg t ggcg cagc tccc tttctacggg t gcgcgt t gcctgcgcgg 7381 ccttccggag cgaggtgtgg gtgagcgcaa aggtgtccct gaccatgact ttgaggtact 7441 ggta t gaa gtc gtgtcg tcgcatccgc cctgctccca gagcaaaaag tccg gcgct 7501 ttttggaacg cggatttggc agggegaagg tgacatcgtt gaagagtatc tttcccgcgc 7561 gaggcataaa gttgcgtgtg tgeggaagg tcccggcac c cggaacgg ttgttaatta 7621 cctgggcggc gagcacgatc tegteaaage cgttgatgtt gtggcccaca atgtaaagtt 7681 ccaagaagcg cgggatgccc ttgatggaag gcaatttttt a ttcctcg t gg g gct 7741 cttcagggga gctgagcccg tgctctgaaa gggcccagtc tgcaagatga gggttggaag 7801 cgacgaatga gc ccac gg tc cgggcca ttagcatttg c ggtggtcg cg aag tcc7861 taaactggcg acctatggcc attttttctg gggtgatgea gtagaaggta agegggtett 792 g cccagcg gtcccatcca aggttegegg etaggteteg cgcggcagtc c t a gag get 7981 catctccgcc gaacttcatg accagcatga agggcacgag ctgcttccca aaggccccca 8041 tccaagtata ggtctctaca tegtaggtga caaagagacg ctcggtgcga ggatgegage 8101 cgatcgggaa gaactggatc tcccgccacc aattggagga gtggctattg atgtggtgaa 8161 agtagaagtc cctgcgacgg gccgaacact cgtgctggct cttgtaaaaa cgtgcgcagt 8221 actggcagcg gtgcacgggc tgtacatcct gcacgaggtt gacctgacga ccgcgcacaa 8281 ggaagcagaci tgggaatttg agcccctcgc ctggcgggtt tggctggtgg tettetaett 8341 cggctgcttg tccttgaccg tetggetget cgaggggagt taeggtggat cggaccacca 8401 cgccgcgcga gcccaa gtc cagatgtccg cgcgcggcgg teggagettg atgacaacat 8461 cgcgcagatg ggagctgtcc atggtctgga gctcccgcgg egteaggtea ggcgggagct 8521 cc egcaggtt tacctcgcat agaegggtea gggcgcgggc tagatccagg egatacctaa 8581 1: tccagggg ctggttg t geggeg tega tggcttgca gaggccgcat ccccgcggcg 8641 cgactacggt accgcgcggc gggcggtggg ccgcgggggt gtccttggat gatgeateta 8701 aaagcggtga cgcgggcgag cccccggagg tagggggggc tccggacccg ccgggagagg 8761 gggcaggggc acgtcggcgc cgcgcgcggg caggagctgg tgctgcgcgc gtaggttgct 8821 ggcg acgcg acgacgc gc ggttga tc t::: etgaatetgg cgcctctgcg tg agacgac 8881 gggcccggtg agcttgaacc tgaaagagag ttcgacagaa teaatttegg tgtcgttgac 8941 ggcggcctgg cgcaaaatct cctgcacgtc tcctgagttg tettgatagg cg tctcggc 9001 catgaactgc tcgatctctt cctcctggag atctccgcgt ccggctcgct ccacggtggc 9061 ggcg ggtcg ttggaaatgc gggcca t:g g etgegagaag gegttgagge c tccctcgtt 9121 ccagacgcgg ctgtagacca cgcccccttc ggcatcgcgg gcgcgcatga ccacctgcgc 9181 gagattgagc tccacgtgcc gggcgaagac ggcgtagttt cgcaggcgct gaaagaggta 9241 gttgagggtg gtggcggtgt gttctgccac gaagaagtac ataacccagc gtcgcaacgt 9301 ggattcgttg atatccccca aggcctcaag gcgctccatg gcctcgtaga agtccacggc 9361 gaagttgaaa aactgggagt tgcgcgccga cacggttaac tcctcctcca gaagaeggat 9421 gagctcggcg acagtgtcgc gcacctcgcg ctcaaaggct acaggggcct cttcttcttc 9481 ttcaatctcc tcttccataa gggcctcccc ttettettet tctggcggcg gtgggggagg 9541 ggggacacgg cggcgacgac ggcgcaccgg gaggeggteg acaaagcgct cgatcatctc 9601 cccgcggcga cggcgcatgg tctcggtgac, ggcgcggccg ttctcgcggg ggcgcagttg 9661 gaagacgccg cccgtcatgt cccggttatg ggttggcggg gggctgccat gcggcaggga 9721 t cggcgcta acgatgcatc tcaacaa t: t:g ttgtgtaggt actccgccgc cg gggacct 9781 gagcgagtcc gcatcgaccg gateggaaaa cctctcgaga aaggegteta accagtcaca 9841 gtcgcaa gt aggc t g ge a ccgtggcggg c gcagcggg eggeggtegg ggttgtttct 9901 ggcggaggtg etgetgatga tgtaattaaa gtaggeggte ttgagaegge ggatggtcga 9961 cagaagcacc atgtcctt g gtccggcc t:g etgaatgege aggeggtegg cc tgcccca 10021 ggcttcgttt tgacatcggc gcaggtcttt gtagtagtet tgeatgagee tttctaccgg 10081 cacttcttct t ctcc t t c c t cttgtcctgc atetettgea tetategetg cggcggcggc 10141 ggagtttggc cgtaggtggc gccctcttcc tcccatgcgt gtgaccccga agcccctcat 10201 cggctgaagc agggctaggt cggcgacaac gcgctcggct aatatggcct gctgcacctg 10261 cgtgagggta gaetggaagt catccatgtc cacaaagcgg tggtatgege ccgtgttgat 10321 ggtgtaagtg cagttggcca taacggacca gttaaeggte tggtgacccg C^C L C C C <3 o.10381 ctcggtgtac etgagaegeg agtaagccct egagteaaat aegtagtegt tgeaagteeg 10441 caccaggtac tggtatccca ccaaaaagtg cggcggcggc tggeggtaga ggggccagcg 10501 tagggtggcc ggggctccgg gggegagate ttccaacata aggegatgat atccgtagat 10561 g i-acctggac atccaggtga tgccggcggc ggtggtggag gegegeggaa agtcgcggac 10621 gcggttccag atgttgcgca gcggcaaaaa gtgctccatg gtcgggacgc tctggccggt 10681 caggcgcgcg c aa t eg utga cgctctagcg tgcaaaagga gageetgtaa gcgggcactc 10741 ttccgt tc tggtgg taa attcgcaagg gtatcatggc ggacgaccgg ggttcgagcc 10801 ccgtatccgg ccgtccgccg tgatccatgc ggttaccgcc egegtgtega acccaggtgt 10861 gcgacgtcag acaacggggg agtgctcc ttggcttcct tccaggcgcg geggetgetg 10921 cgctagcttt tttggccact ggccgcgcgc agegtaageg gttaggctgg aaagegaaag 10981 cattaagtgg ctcgc tccct gtageeggag g ttattttc caagggttga gtcgcgggac 11041 ccccggttcg agtctcggac cggccggact gcggcgaacg ggggtttgcc tccccgtcat 11101 gcaagacccc gettge aat tcctccggaa acagggacga gccccttttt tgcttttccc 11161 agatgcatcc ggtgetgegg cagatgcgcc cccctcctca gcagcggcaa gagcaagagc 11221 agcggcagac atge gggea ccctcccctc ctcctaccgc gtcaggaggg gcgacatccg11281 cggttgacgc ggcagcagat ggtgattacg aacccccgcg gcgccgggcc cggcactacc 11341 tggacttgga ggagggc ag ggcctggcgc gget ggage gccctctcct gagcggc cc 11401 caagggtgca gctgaagcgt gatacgcgtg aggegtaegt gccgcggcag aacctgtttc 11461 gcgaccgcga gggagaggag cccgaggaga tgcgggatcg aaagttccac gcagggcgcg 11521 agctgcggca tggcctgaat cgcgagcggt tgetgegega ggaggacttt gagcccgacg 11581 cgcgaaccgg gattagtccc gcgcgcgcac aegtggegge cgccgacctg gtaaccgcat 11641 acgagcagac ggtgaaccag gagattaact ttcaaaaaag ctttaacaac cacgtgcgta 11701 cgcttgtggc gcgcgaggag gtggctatag gaetgatgea tctgtgggac tttgtaagcg 11761 cgctggagca aaacccaaat agcaagccgc teatggegea gctgttcctt atagtgeage 11821 acagcaggga CHHCCjclCjCfCcl ttcagggatg egetgetaaa catagtagag cccgagggcc 11881 gctggctgct cgatttgata aacatcctgc, agagcatagt ggtgeaggag egeagettga 11941 gcctggctga caaggtggcc gccatcaact attccatgct tagcctgggc aagttttacg 12001 cccgc ag t ataccatacc ccttacgt: t:c ccatagacaa ggaggtaaag a txcg ggggt 12061 tctacatgcg catggcgctg aaggtgctta ccttgagcga cgacctgggc gtttatcgca 12121 acgagcgcat ccacaaggcc gtgagcgtga gccggcggcg c g ge t cage gaccgcgagc 12181 tgatgcacag cctgcaaagg gccctggctg gcacgggcag eggegataga gaggeegagt 12241 cc tactttga cgcgggcgct gacctgcgc t: gggcccca g ccgacgcgcc c txjgaggcag 12301 ctggggccgg acctgggctg gcggtggcac ccgcgcgcgc tggcaacgtc ggcggcgtgg 12361 agga tatga cgaggacg t gag tac gage cagaggacgg cgagtactaa geggtgatgt 12421 ttctgatcag atgatgcaag acgcaacgga cccggcggtg cgggcggcgc tgcagagcca 12481 gccgtcccggc cttaactcca cggacgac tag gcgcc ggtc atggaccgca txcatgtcgct 12541 gactgcgcgc aatcctgacg cgttccggca gcagccgcag gccaaccggc tctccgcaat 12601 tctggaagcg gtggtcccgg cgcgcgcaaa ccccacgcac gagaaggtgc tggegategt 12661 aaacgcgctg gccgaaaaca gggccatccg gcccgacgag gccggcctgg tctacgacgc 12721 gctgcttcag cgcgtggctc gttacaacag cggcaacgtg cagaccaacc tggaccggct 12781 ggtgggggat gtgcgcgagg ccgtggcgca gegtgagege gcgcagcagc agggcaacct 12841 gggctccatg gttgcactaa acgccttcct gagtacacag cccgccaacg tgccgcgggg 12901 acaggaggac tacaccaact ttgtgagcgc aetgeggeta atggtgactg agacaccgca 12961 aagtgaggtg taccagtctg ggccagacta ttttttccag accagtagac aaggeetgea 13021 gaccgtaaac ctgagccagg ctttcaaaaa cttgcagggg ctgtgggggg tgcgggctcc 13081 cacaggcgac cgcgcgaccg tgtetagett gctgacgccc aactcgcgcc tgttgctgct 13141 gc taat gcg cccttcacgg acagtggcag cgtgtcccgg gacacatacc teaggteaett 13201 gctgacactg taccgcgagg ccataggtca ggcgcatgtg gacgagcata ctttccagga 13261 gattacaagt g cagccgcg cgctggggc ggaggacacg ggc gcctgg aggcaaccct 13321 aaactacctg ctgaccaacc ggcggcagaa gatcccctcg ttgcacagtt taaacagcga 13381 ggagg gcgc attttgc ct aegtgeagea g gegtg ge cttaacctga t jc gcga egg 13441 ggtaacgccc agcgtggcgc tggacatgac cgcgcgcaac atggaaccgg gcatgtatgc 13501 ctca ccgg ccgt t: tea tea accgcctaat ggactacttg c tcgcgcgg ccgccgtgaa 13561 ccccgagtat ttcaccaatg ccatcttgaa cccgcactgg ctaccgcccc ctggtttcta 13621 caccggggga ttcgaggtgc ccgagggtaa egatggatte ctctgggacg acatagacga 13681 cagcgtgttt tccccgcaac cgcagaccct gctagagttg caacagcgcg agcaggcaga 13741 ggcggcgctg cgaaaggaaa gcttccgcag gccaagcagc ttgtccgatc taggegetge 13801 ggccccgcgg tcagatgcta gtagcccatt tccaagcttg atagggtctc ttaccagcac 13861 tcgcaccacc cgcccgcgcc tgctgggcga ggaggagtac ctaaacaact cgctgctgca 13921 gccgcagcgc gaaaaaaacc tgcctccggc atttcccaac aacgggatag agagcctagt 13981 ggacaagatg agtagatgga agaegtaege gcaggagcac agggacgtgc caggcccgcg 14041 cccgcccacc cgtcgtcaaa ggcacgaccg tcagcggggt ctggtgtggg aggaegatga 14101 ctcggcagac gacagcagcg tcctggattt gggagggagt ggcaacccgt ttgcgcacct 14161 tcgcccc gg ctggggag tgttttaaaa ci ci ci ci ci 333 CJ C atgatgeaaa a t a a a a a a c t 14221 caccaaggcc atggcaccga gcgttggttt tettgtatte cccttagtat gcggcgcgcg 14281 gcga tcgt tg agg ggtcc txxctxxxctxxc t eg gagtg t gtgagege ggcgcc gtg 14341 gcggcggcgc tgggttctcc ettegatget cccctggacc cgccgtttgt gcctccgcgg 14401 t cct c gc ctaccggggg gagaa cagc atxxxjttac t: ctg gttggc acccctattx: 14461 gacaccaccc gtgtgtacct ggtggacaac aagteaaegg atgtggcatc cctgaactac 14521 cagaacgacc acagcaactt tctgaccacg gtc ttca acaatgacta cagcccgggg 14581 gaggcaagca cacagaccat caatcttgac gaccggtcgc actggggcgg cgacctgaaa 14641 accatcctgc a ti a c c a a c a t gccaaatgtg aacgagttca tcgtttaccaa taagtttaag14701 gcgcgggtga tggtgtcgcg cttgcctact aaggacaatc aggtggagct gaaatacgag 14761 gggtggagt tcacgctgcc cgagggcaac tactccgaga ccatgaccat agacctt tg 14821 aacaacgcga tcgtggagca ctacttgaaa gtgggcagac agaacggggt tctggaaagc 14881 gacatcgggg taaagtttga cacccgcaac ttcagactgg ggtttgaccc cgtcactggt 14941 cttgtcatgc ctggggtata tacaaacgaa gccttccatc cagacatcat tttgctgcca 15001 ggatgcgggg tggacttcac ccacagccgc ctgagcaact tgttgggcat ccgcaagcgg 15061 caacccttcc aggagggctt taggatcacc tacgatgatc tggagggtgg taacattccc 15121 gcactgttgg atgtggacgc ctaccaggcg agcttgaaag atgacaccga 3C3 C 15181 ggtggcgcag gcggcagcaa cagcagtggc agcggcgcgg aagagaactc caacgcggca 15241 gccgcggcaa tgcagccggt ggaggacatg aacgatcatg ccattcgcgg cgacaccttt 15301 gccacacggg ctgaggagaa gcgcgctgag gccgaagcag cggccgaagc tgccgccccc 15361 gctgcgcaac ccgaggtcga gaagcctcag aagaaaccgg tgatcaaacc cc ugacagag 15421 gacagca ga aacgcagtta caacctaa t:a agca tgac gcaccttx:ac cc gt ccgc 15481 agctggtacc ttgcatacaa ctacggcgac cctcagaccg gaatccgctc atggaccctg 15541 ctttgcactc ctgacgc ac ctgcggctxrg gagcaggtx: t: actggtcgtt gccagacatg 15601 atgcaagacc ccgtgacctt ccgctccacg cgccagatca gcaactttcc ggtggtgggc 15661 gccg gctgt tgcccgtgca ctxx:aag gc ttctacaacg ccaggccgt c tactcccaa 15721 ctcatccgcc agtttacctc tctgacccac gtgttcaatc gctttcccga gaaccagatt 15781 ttggcgcgcc cgccagcccc caccatcacc accgtx:agtg aaaacgttcc tgctx:tx:aca 15841 gatcacggga cgctaccgct gcgcaacagc atcggaggag tccagcgagt gaccattact 15901 gacgccagac gccgcacctg cccctacgt: t: tacaaggccc tgggcatagt c txxjccgcgc 15961 gtcctatcga gccgcacttt ttgagcaagc, atgtccatcc ttatatcgcc cagcaataac 16021 acaggctggg gcctgcgctt cccaagcaag atgtttggcg gggccaagaa gcgctccgac 16081 caacacccag tgcgcgtgcg cgggcactac cgcgcgccct ggggcgcgca caaacgcggc 16141 cgcactgggc gcaccaccgt cgatgacgcc atcgacgcgg tggtggagga ggcgcgcaac 16201 tacacgccca cgccgccacc agtgtccaca gtggacgcgg ccattcagac cgtggtgcgc 16261 ggagcccggc gctatgctaa aatgaagaga cggcggaggc gcgtagcacg tcgccaccgc 16321 cgccgacccg gcactgccgc ccaacgcgcg gcggcggccc, tgcttaaccg cgcacgtcgc 16381 accggccgac gggcggccat gcgggccgct cgaaggctgg ccgcgggtat tgtcactgtg 16441 ccccccaggt ccaggcgacg agcggccgcc gcagcagccg cggccattag tgctatgact 16501 cagggtcgca ggggcaacgt gtattgggtg cgcgactcgg ttagcggcct gcgcgtgccc 16561 g t:gcgcaccc gccccccgcg caactaga t: t: gcaagaaaaa actacttaga c t:cgtactgt 16621 tgtatgtatc cagcggcggc ggcgcgcaac gaagctatgt ccaagcgcaa aatcaaagaa 16681 gag tgctxx: aggtx:a t:cgc gccgg g tx: tatggccccc cg g gga agagcaggat 16741 tacaagcccc gaaagctaaa gcgggtcaaa aagaaaaaga aagatgatga tgatgaactt 16801 gacg cg gg tggaactgct gcacgc tacc gcgcccaggc gacgggtaca gtxjg ggt 16861 cgacgcgtaa aacgtgtttt gcgacccggc accaccgtag tctttacgcc cggtgagcgc 16921 tccacccgca cctaca gcg cgtgt tg t gaggtgtacg gcg cg gga cctgcttgag 16981 caggccaacg agcgcctcgg ggagtttgcc tacggaaagc, ggcataagga catgctggcg 17041 ttgccgctgg acgagggcaa cccaacacct agcctaaagc ccgtaacact gcagcaggtg 17101 ctgcccgcgc ttgcaccgtc cgaagaaaag cgcggcctaa agcgcgagtc tggtgacttg 17161 gcacccaccg tgcagctgat ggtacccaag cgccagcgac tggaagatgt cuggaaaaa 17221 atgaccgtgg aacctgggct ggagcccgag gtccgcgtgc, ggccaatcaa gcaggtggcg 17281 ccgggactgg gcgtgcagac cgtggacgtt cagataccca ctaccagtag caccagtatt 17341 gccaccgcca cagagggcat ggagacacaa acgtccccgg ttgcctcagc ggtggcggat 17401 gccgcggtgc aggcggtcgc tgcggccgcg tccaagacct ctacggaggt gcaaacggac 17461 ccgtggatgt ttcgcgtttc agccccccgg cgcccgcgcc, gttcgaggaa gtacggcgcc 17521 gccagcgcgc tactgcccga atatgcccta catccttcca ttgcgcctac ccccggctat 17581 cgtggctaca cctaccgccc cagaagacga gcaactaccc gacgccg c caccactgga 17641 acccgccgcc gccgtcgccg tcgccagccc gtgctggccc cgatttccgt gcgcagggtg 17701 gc txxjcg g gaggcaggac cctggtgc t:g ccaacagcgc gctaccaccc cagc tcgtt 17761 taaaagccgg tctttgtggt tcttgcagat atggccctca cctgccgcct ccgtttcccg 17821 gtgccgggat txxxjaggaag aatgcaccgt aggaggggca t:ggccggcc cggcctgacg 17881 ggcggcatgc gtcgtgcgca ccaccggcgg cggcgcgcgt cgcaccgtcg catgcgcggc 17941 ggt:a t:cctgc ccctccttat txx:actga tx: gccgcggcg ttggcgccgt gcccggaatt 18001 gcatccgtgg ccttgcaggc gcagagacac tg ttaaaaa caagttgcat gtggaaaaat 18061 c a a a a t a a a a agtx: txjgact ctcacgctxrg cttgg txx:tg taactatttt gtagaatgga18121 agacatcaac tttgcgtctc tggccccgcg acacggctcg cgcccgttca tgggaaactg 18181 gcaagata c ggcaccagca ata tgagegg t ggcg ■■''■■■' I-agc ggggct cgctgtggag 18241 cggcattaaa aatttcggtt ccaccgttaa gaactatggc agcaaggcct ggaacagcag 18301 cacaggccag atgctgaggg ataagttgaa agagcaaaat ttccaacaaa aggtggtaga 18361 tggcctggcc tctggcatta gcggggtggt ggacctggcc, aaccaggcag tgcaaaataa 18421 gattaacagt aagcttgatc cccgccctcc cgtagaggag cctccaccgg ccgtggagac 18481 agtgtctcca gaggggcgtg gegaaaageg tccgcgcccc gacagggaag aaactctggt 18541 gacgcaaata gacgagcctc cctcgtacga ggaggcacta aagcaaggcc tgcccaccac 18601 ccgtcccatc gcgcccatgg ctaccggagt gctgggccag cacacacccg taacgctgga 18661 cctgcctccc cccgccgaca cccagcagaa acctgtgctg ccaggcccga ccgccgttgt 18721 tgtaacccgt cctagccgcg cgtccctgcg ccgcgccgcc agcggtccgc gatcgttgcg 18781 gcccgtagcc agtggcaact ggcaaagcac actgaacagc atcgtgggtc ugggggt gc 18841 a tccctgaag cgccgac at get tetga ta gct cgtgt c atgtg tg tea tgta gc 18901 gtccatgtcg ccgccagagg agetgetgag ccgccgcgcg cccgctttcc aagatggcta 18961 ccccttcgat ga tgccgcag tggtc aca tgcaca tctc gggcc gg c gcctcggagt 19021 acctgagccc cgggctggtg cagtttgccc gcgccaccga gacgtacttc ageetga ata 19081 acaagtttag aaaccccacg gtggcgcc ta cgcacgacgt gaccacagac cggtcccagc 19141 gtttgacgct gcggttcatc cctgtggacc gtgaggatac tgcgtactcg tacaaggcgc 19201 gg caccct agctgtgggt gataaccgtg c ggaca t: ggcttcc cg tactttgaca 19261 tccgcggcgt gctggacagg ggccctactt ttaagcccta ctctggcact gcctacaacg 19321 ccctggctcc caagggt cc ccaaa tee 11 gcgaatggga aagctgct ac tgctcttg 19381 aaataaacct agaagaagag gacgatgaca acgaagacga agtagacgag caagctgagc 19441 tcacgtattt gggcaggcgc cttattctgg tataaatatt clCcl<d<d C[ciC[C[ 19501 gtattcaaat aggtgtcgaa ggtcaaacac ctaaatatgc cgataaaaca tttcaacctg 19561 aacctcaaat aggagaatct cagtggtacg aaacagaaat taatcatgca gctgggagag 19621 t c c e a a a a a a gactacccca atgaaaccat gttacggttc atatgcaaaa cccacaaatg 19681 3333 L- 3 gcaaggcatt ettgtaaage aacaaaatgg aaagctagaa ag i-caagtgg 19741 aaatgcaatt tttctcaact actgaggcag ccgcaggcaa tggtgataac ttgactccta 19801 aagtggtatt gtacag ugaa gatgtagata tagaaacccc agacactcat atttcttaca 19861 tgcccactat taaggaaggt aactcacgag aactaatggg ccaacaatct atgcccaaca 19921 ggcctaatta cattgctttt agggacaatt ttattggtct aatgtattac aacagcacgg 19981 g taa tatggg tgttctggcg ggccaagca t cgcagttg c gttg ta ga tttgeaag 20041 acagaaacac agagctttca taccagcttt tgcttgattc cattggtgat agaaccaggt 20101 actt c at gtgg a tcag gc g gaca cta ga tec agatgttaga attattgaaa 20161 atcatggaac tgaagatgaa cttccaaatt actgctttcc actgggaggt gtgatta ata 20221 cagagactct t cc ag ta aaacctaaaa c ggtcagga aaa gga gg gaaaaag tg 20281 ctacagaatt ttcagataaa aatgaaataa gagttggaaa taattttgcc atggaaatca 20341 tctaaatgc caacc tgtgg agaaatttcc tgtac tccaa catagcgc g ta t cccg 20401 acaagctaaa gtacagtcct tccaacgtaa aaatttctga taacccaaac acctacgact 20461 acatgaacaa gcgagtggtg gctcccgggc tagtggactg ctacattaac cttggagcac 20521 gctggtccct tgactatatg gacaacgtca acccatttaa ccaccaccgc aatgctggcc 20581 tgcgctaccg ctcaatgttg ctgggcaatg gtcgctatgt gcccttccac atccaggtgc 20641 ctcagaagtt ctttgccatt aaaaacctcc ttctcctgcc, gggctcatac acctacgagt 20701 ggaacttcag gaaggatgtt aacatggttc tgcagagctc cctaggaaat gacctaaggg 20761 ttgacggagc cagcattaag tttgatagca tttgccttta cgccaccttc ttccccatgg 20821 CCCdCclclCdC cgcctccacg cttgaggcca tgcttagaaa cgacaccaac gaccagtcct 20881 ttaacgacta tctctccgcc gccaacatgc tctaccctat acccgccaac gctaccaacg 20941 tgcccatatc catcccctcc cgcaactggg cggctttccg cggctgggcc ttcacgcgcc 21001 ttaagactaa ggaaacccca tcactgggct cgggc tacga cccttattac ace ac etg 21061 gctctatacc ctacctagat ggaacctttt acctcaacca cacctttaag aaggtggcca 21121 t cctttga ctcttct tc age tggee tg gc tgaccg cc c acc cccaacgagt 21181 ttgaaattaa gcgctcagtt gacggggagg gttacaacgt tgcccagtgt aacatgacca 21241 a g c cctggt caa ge ge actataaca t: tggc accag ggettetata 21301 tcccagagag ctacaaggac cgcatgtact ccttctttag aaacttccag cccatgagcc 21361 g tcaggtggt gg tg tact aaa tacaagg actaccaaca ggtgggca tc c tacaccaac 21421 acaacaactc tggatttgtt ggctaccttg cccccaccat gcgcgaagga caggcctacc 21481 ctgctaactt cccc ta tccg ettataggea a accgca t: tgacagcatt acxx:agaaaa21541 agtttctttg cgatcgcacc ctttggcgca tcccattctc cagtaacttt atgtccatgg 21601 gcgcactcac agacctgggc caaaacc t: tc tctacgccaa ctccgcccac gcgctagaca 21661 tgacttttga ggtggatccc atggacgagc, ccacccttct ttatgttttg tttgaagtct 21721 t i-gacgtggt ccgtgtgcac cagccgcacc gcggcgtcat cgaaaccgtg tacctgcgca 21781 cgcccttctc ggccggcaac gccacaacat aaagaagcaa gcaacatcaa caacagctgc 21841 cgccatgggc tccagtgagc aggaactgaa agccattgtc aaagatcttg gttgtgggcc 21901 atattttttg ggcacctatg acaagcgctt tccaggcttt gtttctccac acaagctcgc 21961 ctgcgccata gtcaatacgg ccggtcgcga gactgggggc gtacactgga tggcctttgc 22021 ctggaacccg c a c t c a a a a a catgctacct ctttgagccc, tttggctttt ctgaccagcg 22081 actcaagcag gtttaccagt ttgagtacga gtcactcctg cgccgtagcg ccattgcttc 22141 ttcccccgac cgctgtataa cgctggaaaa gtccacccaa agcgtacagg ggcccaactc 22201 ggccgcctgt ggactattct gctgcatgtt tctccacgcc tttgccaact ggccccaaac 22261 tccca tggat cacaacccca ccatgaacc t: tattaccggg gtacccaact cca tgctcaa 22321 cagtccccag gtacagccca ccctgcgtcg caaccaggaa cagctctaca gcttcctgga 22381 gcgccactcg ccctac tcc gcagcc cag t cgcagat aggagcgcca cttctttttg 22441 tcacttga 0.0. aacatgtaaa aataatg t c tagagacact ttcaataaag gcaaatgctt 22501 t a t: tgtac actctcgggt gat a tac ccccaccctt gcc tctgcg ccgtttaaaa 22561 atcaaagggg ttctgccgcg catcgctatg cgccactggc agggacacgt tgcgatactg 22621 gtgttta tg ctccac taa actcaggcac aaccatccgc ggcagctcgg tgaagttttc 22681 actccacagg ctgcgcacca tcaccaacgc gtttagcagg tcgggcgccg atatcttgaa 22741 g tcgcagttg gggcctccgc cx:tgcgcgcg cgagttgcga tacacagggt tgcagcactg 22801 gaacactatc agcgccgggt ggtgcacgct ggccagcacg ctcttgtcgg agatcagatc 22861 cgcgtccagg tcctccgcgt tgctcagggc gaacggagtc aactttggta gctgccttcc 22921 caaaaagggc gcgtgcccag gctttgagtt gcactcgcac, cgtagtggca tcaaaaggtg 22981 accgtgcccg gtctgggcgt taggatacag cgcctgcata aaagccttga tctgcttaaa 23041 agccacctga gcctttgcgc cttcagagaa gaacatgccg caagacttgc cggaaaactg 23101 attggccgga caggccgcgt cgtgcacgca gcaccttgcg tcggtgttgg agatctgcac 23161 cacatttcgg ccccaccggt tcttcacgat cttggccttg ctagactgct ccttcagcgc 23221 gcgctgcccg ttttcgctcg tcacatccat ttcaatcacg tgctccttat ttatcataat 23281 gcttccgtgt agacacttaa gctcgccttc gatctcagcg cagcggtgca gccacaacgc 23341 gcagcccgtg ggctcgtgat gcttgtaggt cacctctgca aacgactgca ggtacgcctg 23401 c gga tcgc cccatcatcg tcacaa gg cttgttgctg gtgaaggtca gc gcaaccc 23461 gcggtgctcc tcgttcagcc aggtcttgca tacggccgcc agagcttcca cttggtcagg 23521 cagtagtttg aagt cgcct ttagatcgtt atccacgtgg acttgtcca tc cgcgcg 23581 cgcagcctcc atgcccttct cccacgcaga cacgatcggc acactcagcg ggttcatcac 23641 cgtaa tttca ctttcxrgctt cgctgggc c ttcctcttcc tcttgcgtcc gca taccacg 23701 cgccactggg tcgtcttcat tcagccgccg cactgtgcgc ttacctcctt tgccatgctt 23761 gattagcacx: ggtggg tgc tgaaacccac catttgtagc gccacatctt ctctttcttc 23821 ctcgctgtcc acgattacct ctggtgatgg cgggcgctcg ggcttgggag aagggcgctt 23881 ctttttcttc ttgggcgcaa tggccaaatc cgccgccgag gtcgatggcc gcgggctggg 23941 tgtgcgcggc accagcgcgt cttgtgatga gtcttcctcg tcctcggact cgatacgccg 24001 cctcatccgc ttttttgggg gcgcccgggg aggcggcggc gacggggacg gggacgacac 24061 gtcctccatg gttgggggac gtcgcgccgc accgcgtccg cgctcggggg tggtttcgcg 24121 ctgctcctct tcccgactgg ccatttcctt ctcctatagg c ci g ci o. o. o. o. ga tcatggagtc 24181 agtcgagaag aaggacagcc taaccgcccc ctctgagttc gccaccaccg cctccaccga 24241 tgccgccaac gcgcctacca ccttccccgt cgaggcaccc ccgcttgagg aggaggaagt 24301 gattatcgag caggacccag gttttgtaag cgaagacgac, gaggaccgct cagtaccaac 24361 agaggataaa aagcaagacc aggacaacgc agaggcaaac gaggaacaag tcgggcgggg 24421 ggacgaaagg catggcgact acctag tgt gggagacgac gtgctgttga agcatctgca 24481 gcgccagtgc gccattatct gcgacgcgtt gcaagagcgc agcgatgtgc ccctcgccat 24541 agcggatgtc agccttgcct acgaacgcca cctattctca ccgcgcgtac cccccaaacg 24601 ccaagaaaac ggcacatgcg agcccaaccc gcgcctcaac ttctaccccg tatttgccgt 24661 gccagag tg cttgccacct atcacatctt tttccaaaac tgcaagatac ccctatcctg 24721 ccgtgccaac cgcagccgag cggacaagca gctggccttg cggcagggcg ctgtcatacc 24781 tga tatcgcc tcgctcaacg aagtgccaaa aatctttgag ggtcttggac gcgacgagaa 24841 gcgcgcggca aacgctctgc aacaggaaaa C gcg u gaaagtcact ctggagtgtt 24901 ggtggaactc gaggg gaca acgcgcgcct agccgtacta aaacgcagca tcgaggtcac24961 ccactttgcc tacccggcac ttaacctacc ccccaaggtc atgagcacag c a t g a g t g a.2502 gc tgatc tg cgccgtgcgc agcccc tgga g ggg tgc aatttgcaa aacaaacaga 25081 ggagggccta cccgcagttg gcgacgagca gctagcgcgc tggc.ttc.aaa cgcgcgagcc 25141 tgccgacttg gaggagcgac gcaaactaat gatggccgca gtgctcgtta ccgtggagct 25201 tgagtgcatg cagcggttct ttgctgaccc ggagatgcag cgcaagctag aggaaacatt 25261 gcactacacc tttcgacagg gctacgtacg ccaggcctgc aagatctcca aegtggaget 25321 ctgcaacctg gtctcctacc ttggaatttt gcacgaaaac cgccttgggc aaaaegtget 25381 tcattccacg ctcaagggcg aggcgcgccg cgactacgtc cgcgactgcg tttaettatt 25441 tctatgctac acctggcaga cggccatggg cgtttggcag cagtgcttgg aggagtgeaa 25501 cctcaaggag ctgcagaaac tgctaaagca aaacttgaag gacctatgga cggccttcaa 25561 cgagcgctcc gtggccgcgc ac.c.tggcgga catcattttc cccgaacgcc tgcttaaaac 25621 CC UtfCddCdCJ ggtctgccag acttcaccag tc aaa gcatg ttgcagaact eaggaaett 25681 t tcct gag cgctcaggaa tcttgcccgc cacctgctgt gcact tecta gcgactttgt 25741 gcccattaag taccgcgaat gccctccgcc gctttggggc cactgctacc ttetgeaget 25801 agccaactac cttgcc tacc actctgacat aatggaagac gt gcggtg acggtctact 25861 ggagtgtcac tgtcgctgca acctatgcac cccgcaccgc tccctggttt gcaattcgca 25921 gc tgcttaac g a a a g t c. a a a ttatcggtac ctttgagctg cag gtccct cgcct cga 25981 aaagtccgcg gctccggggt tgaaactcac tccggggctg tggaegtegg cttaccttcg 26041 caaattt ta cctgaggact acc cgccca cgagattagg ttet egaag accaatcccg 26101 cccgcctaat gcggagctta ccgcctgcgt cattacccag ggccacattc ttggccaatt 26161 gcaagcc tc aacaaagccc gccaagagt t tctgctacga ag gacggg gggtttactt 26221 ggacccccag tccggcgagg agctcaaccc aatccccccg ccgccgcagc cctatcagca 26281 gcagccgcgg gcccttgctt cccaggatgg cacccaaaaa gaagetgeag ctgccgccgc 26341 cacccacgga cgaggaggaa tactgggaca gtcaggcaga ggaggttttg gaegaggagg 26401 aggaggacat gatggaagac tgggagagcc tagacgagga agcttccgag gtegaagagg 26461 tgtcagacga aacaccgtca ccctcggtcg cattcccctc gccggcgccc cagaaatcgg 26521 caaccggttc cagcatggct acaacctccg ctcctcaggc gccgccggca ctgcccgttc 26581 gccgacccaa ccgtagatgg gacaccactg gaaccagggc cggtaagtcc aagcagccgc 26641 cgccgttagc ccaagagcaa caacagcgcc aaggctaccg ctcatggcgc gggcacaaga 26701 acgccatagt tgcttgcttg caagactgtg ggggcaacat ctccttcgcc cgccgctttc 26761 ttctctacca tcacggcgtg gccttccccc gtaacatcct gcattactac cgtcatctct 26821 acagcccata ctgcaccggc ggc gcggca gc ac gc g cggccacaca gaa ca gg 26881 cgaccggata gcaagactct gacaaagccc aagaaatcca cagcggcggc agcagcagga 26941 ggaggagcgc tgc tc t gc gcccaacgaa cccgtatcga cccgcgagct tagaaacagg 27001 atttttccca ctctgtatgc tatatttcaa cagagcaggg gccaagaaca agagetg o. o. o.27061 ci ci ci ci ci ci ci (33 ggtctctgcg tccctcacc cgcagctgcc t tatcacaa aagega g t 27121 cagcttcggc gcacgctgga agacgcggag gctctcttca gtaaatactg cgcgctgact 27181 cttaaggact agtt tcgcgc cctttc caa atttaagcgc gaa ct cg tc tctccag 27241 cggccacacc cggcgccagc acctgttgtc agcgccatta tgagcaagga aattcccacg 27301 ccctacatgt ggagttacca gccacaaatg ggacttgcgg ctggagctgc ccaagactac 27361 tcaacccgaa taaactac.at gagcgcggga ccccacatga tatccc.gggt caacggaata 27421 cgcgcccacc gaaaccgaat tctcctggaa caggcggcta ttaccaccac acctcgtaat 27481 a a c c 1. a a t c cccgtagttg gcccgctgcc ctggtgtacc aggaaagtcc cgctcccacc 27541 actgtggtac ttcccagaga cgcccaggcc gaagttcaga tgactaactc aggggcgcag 27601 cttgcgggcg gctttcgtca c.agggtgcgg tcgcccgggc agggtataac tcacctgaca 27661 3 LCclCj<3C[C[C[C gaggtattca gctcaacgac gagtcggtga gctcctcgct tggtctccgt 27721 ccggacggga catttcagat cggcggcgcc ggccgctctt cattcacgcc tegteaggea 27781 atcctaactc tgcagacctc gtcctctgag ccgcgctctg gaggcattgg aactctgcaa 27841 tttattgagg agtt tgt cc atcggtctac tttaacccct tctcgggacc tcccggccac 27901 tatccggatc aatttattcc taactttgac gcggtaaagg actcggcgga cggctacgac 27961 tga t tt a gtggagaggc agagcaac tg cgcctgaa c acctggtcca c tgtcgccgc 28021 cacaagtgct ttgcccgcga ctccggtgag ttttgctact ttgaattgee cgaggatcat 28081 atcgagggcc cggcgcac g cgtccggctt accgcccagg g gettge ccgtagcctg 28141 attcgggagt ttacccagcg ccccctgcta gttgagcggg acaggggacc ctgtgttctc 28201 ac tgtgattt gcaactgtcc taaccc tgga ttacatcaag tcctctagt taatgteagg 28261 tcgcctaagt cgattaacta gagtacccgg ggatcttatt ccctttaact aataaaaaaa 28321 aata taaag catcac tt c ttaaaatcag ttagcaaat t tctgtccagt tt ttcagca28381 gcacctcctt gccctcctcc cagctctggt attgcagctt cctcctggct gcaaactttc 28441 tccacaatct aa gg a g cagtt tec t: cctgttcctg cca ccgca cccactatct 28501 tcatgttgtt gcagatgaag cgcgcaagac, cgtctgaaga taccttcaac cccgtgtatc 285 & 1 ggaaaccggt cctccaactg tgccttttct tactcctccc tttgtatccc 28621 ccaatgggtt tcaagagagt ccccctgggg tactctcttt gcgcctatcc gaacctctag 28681 ttacctccaa tggcatgctt gcgctcaaaa tgggcaacgg cctctctctg gacgaggccg 28741 gcaaccttac ctcccaaaat gtaaccactg tgagcccacc tctcaaaaaa accaagtcaa 28801 aca aaaacct ggaaatatet gcacccctca cagttacctc agaagcccta ac egtggctq 28861 ccgccgcacc tetaatggte gcgggcaaca cactcaccat gcaatcacag gccccgctaa 28921 ccgtgcacga ctccaaactt agcattgcca cccaaggacc cctcacagtg tcagaaggaa 28981 agctagccct gcaaacatca ggccccctca ccaccaccga tagcagtacc cttactatca 29041 ctgcctcacc ccctctaact actgccactg gtagcttggg cattgacttg cl cl cl <3 C C C ci 29101 1: t tacaca a a a t g g a a a a c aggac taa agtacggggc ee tgea t g aacagacg 29161 acctaaacac tttgaccgta gcaactggtc caggtgtgac tatt o. o. t o. at acttccttgc 29221 a a a c ti a a a g t taetggagee ttgggttttg a cacaagg caatatgcaa ct aatgtag 29281 caggaggact aaggattgat tctcaaaaca gacgccttat acttgatgtt agttatccgt 29341 t tga tgctca aaaccaacta aa ctaagac t gg c ggg ccc ctt tt a ta actcag 29401 cccacaactt ggatattaac tacaacaaag gcctttactt gtttacagct tcaaacaatt 29461 ccaaaaagct tgaggt t ac ctaagcactg ccaaggggt t: g tgtttgac gc acagcca 29521 tagccatt a a tgcaggagat gggcttgaat ttggttcacc taatgcacca aacacaaatc 29581 ccc tcaaaac aaaaat ggc ca ggcc tag aatttgattc aaacaaggct a tggt tecta 29641 aactaggaac tggeettagt tttgacagca caggtgccat tacagtagga a a c, a a a a a t a 29701 a eg a uaagct aactttgtgg accacaccag ctcc CL tctcc taaetgtaga c caaatgeag 29761 agaaagatgc taaactcact ttggtcttaa caaaatgtgg cagtcaaata cttgctacag 29821 tttcagtttt ggctgttaaa ggcagtttgg ctccaatatc eggaacagtt caaagtgctc 29881 atcttattat aagatttgac gaaaatggag tgctactaaa caattccttc ctggacccag 29941 aa i.a c ggaa etttagaaat ggagatctta ctgaaggcac agcctataca aacgctgttg 30001 gatttatgcc taacctatca gcttatccaa aatctcacgg taaaaetgee aaaagtaaca 30061 ttgtcagtca agtttactta aacggagaca aaactaaacc tgtaacacta accattacac 30121 taaacggtac acaggaaaca ggagacacaa ctccaagtgc atactctatg tcattttcat 30181 gggactggtc tggccacaac tacattaatg aaatatttgc cacatcctct tacacttttt 30241 c tac ttgc cca ga aa agaa tcgt t: t: gtgtt tgtt eaaegtg tt t tttttcaa 30301 ttgcagaaaa tttcaagtca tttttcattc agtagtatag ccccaccacc acatagctta 30361 cagatcac eg t ace tt a c ac cac agaaccctag tattcaacc gee acc ccc 30421 tcccaacaca cagagtacac agtcctttct ccccggctgg ccttaaaaag catcatatca 30481 tgggt ac g aca t ctt agg tgt t t ttcc cacgg ee g eg agccaa cgc 30541 tcatcagtga tattaataaa ctccccgggc agctcactta agttcatgtc gctgtccagc 30601 tgctgagcca caggc tgctg tcc acttgc ggttgctta egggeggega aggagaag e 30661 cacgcctaca tgggggtaga gtcataatcg tgcatcagga tagggcggtg gtgetgeage 30721 agcgcgcgaa taaaetgetg ccgccgccgc tccgtcctgc aggaatacaa catggcagtg 30781 gtctcctcag egatgatteg caccgcccgc agcataaggc gccttgtcct ccgggcacag 30841 cagcgcaccc tgatctcact taaatcagca cagtaactgc agcacagcac cacaata tg 30901 ttcaaaa cc cacagtgcaa ggcgctgtat ccaaagctca tggcggggac cacagaaccc 30961 acgtggccat cataccacaa gcgcaggtag attaagtggc gacccctcat aaacacgctg 31021 gacataaaca ttacctcttt tggcatgttg taattcacca cctcccggta ccatataaac 31081 ctctgatt dd acatggcgcc atccaccacc atcctaaacc agctggccaa aacctgcccg 31141 ccggctatac aetgeaggga accgggactg gaacaatgac, agtggagagc ccaggactcg 31201 taaccatgga tcatcatgct egteatgata tcaatgttgg cacaacacag gcacacgtgc 31261 c c cc tcagga tt c aagctcctcc cgcg taga cc t tccca gggaacaacc 31321 cattcctgaa teagegtaaa tcccacactg cagggaagac ctcgcacgta actcacgttg 31381 tgca ttgtca aag g aca cgggcagc agcgg tg t cc ccag a t ggt gegegg 31441 gtttctgtct CciclclclCfCfclCjCj tagacgatcc ctactgtacg gagtgegeeg agacaaccga 31501 g cg g g gteg tagtgt catgccaaat ggaacgccgg aegtagteat at cc gaa 31561 gcaaaaccag gtgcgggcgt gacaaacaga tctgcgtctc cggtctcgcc gettagateg 31621 c tc tgtgt g g g agt a a tee ac tc tctcaaagca ccaggcgcc ccctggcttc 31681 gggttctatg t a a a c ucctt catgcgccgc tgccctgata acatccacca ccgcagaata 31741 agccacaccc agccaaccta cacattcgtt c gcgagtca c c egggag gagegggaag31801 d Q Cj 33 Q o. accatgtttt tttttttatt C C 3.3.3. agatt atccaaaacc tcaaaatgaa 31861 ga tc tattaa gtgaaegege tcccctccgg tggcgtggtc aaactctaca gccaaagaac 31921 agataatggc atttgtaaga tgttgcacaa tggcttccaa aaggcaaacg gccctcacgt 31981 ccaagtggac gtaaaggeta aacccttcag ggtgaatctc ctctataaac attccagcac 32041 cttcaaccat tg c c c si 5i 5it a a ttctcatctc gccaccttct caatatatct ctaagcaaat 32101 cccgaatatt aagtccggcc attgtaaaaa tctgctccag agcgccctcc accttcagcc 32161 tcaagcagcg aatcatgatt Q C- 3.333333 C aggttcctca cagacctgta taagattcaa 33CjCCjC[33C3 ttaacaaaaa taccgcgatc ccgtaggtcc cttcgcaggg ccagctgaac 32281 ataatcgtgc aggtctgcac ggaccagcgc ggccacttcc ccgccaggaa ccatgacaaa 32341 agaacccaca c t ga u uatga cacgcatact cggagctatg ctaaccagcg tagccccgat 32401 gtaagcttgt tgcatgggcg gcgatataaa atgcaaggtg ctgctcaaaa aatcaggcaa 32461 agcctcgcgc aaaaaagaaa gcacatcgta gtcatgctca tgcagataaa ggcaggtaag 32521 c tccggaacc cl C. C cl C cl g a a ci aagacacca t ttttctctca aacatgtctg cgggtttctg 32581 cataaacaca aaataaaata acaaaaaaac atttaaaca tagaagcctg tcttacaaca 32641 ggaaaaacaa ccct ta taag cataagacgg actacggcca tgccggcgtg accgtaaaaa 32701 aactggtcac cgtgattaaa aagcaccacc gacagctcct cggtcatgtc cggagt c a t a 32761 a tgtaagact cggtaaacac atcagg t tiga ttcactcggt cagtgctaaa aagcgaccga 32821 aatagcccgg gggaatacat acccgcaggc gtagagacaa cattacagcc cccataggag 32881 gtataacaaa a 11 a a t a g g a gagaaaaaca cataaacacc tgaaaaaccc tcctgcctag 32941 gcaaaatagc accctcccgc tccagaacaa catacagcgc ttccacagcg gcagccat 3.3.33001 cagtcagcct t a c c a g t a a a a a a g a a a a c c tattaaaaaa acaccactcg acacggcacc 33061 agctcaatca gtcacagtgt aaaaaagggc caagtgcaga gcgagtatat ataggactaa 33121 aaaa u gac gt aacggttaaa gtccacaaaa aacacccaga aaaccgcacg cgaacctacg 33181 cccagaaacg aaagccaaaa aacccacaac ttcctcaaat cgtcacttcc gttttcccac 33241 gttacgtcac ttcccatttt aagaaaacta caattcccaa cacatacaag ttactccgcc 33301 ctaaaaccta cgtcacccgc cccgttccca cgccccgcgc cacgtcacaa actccaccccc i.ca i-tatca tattggette aatccaaaa aaggtatatt attgatgatgSEQ ID NO: 24: rAd-WS24 nucleotide sequence1 catcatcaat aatatacctt attttggatt gaagccaata tgataatgag ggggtggagt 61 ttgtgacgtg gcgcggggcg tgggaacggg gcgggtgacg tagtagtgtg geggaagtgt 121 gatgttgcaa gtgtggcgga acacatgtaa gegaeggatg uggcaaaagt gacgtttttg 181 gtgtgcgccg gtgtacacag gaagtgacaa ttttcgcgcg gttttaggcg gatgttgtag 241 taaa u u t ggg cgtaaccgag taagatttgg ccattttcgc gggaaaactg 33L.33CJ3CJQ3 301 agtgaaatct gaataatttt gtgttactca tagegegtaa taetgetaga gatetggega 361 aagggggatg tgctgcaagg egattaagtt gggtaaegee agggttttcc cagtcacgac 421 gttgtaaaac gacggccagt gaattgtaat acgactcact a tagggcgaa ttgggtactg 481 gccacaggag cttggcccat tgcatacgtt gtatccatat cataatatgt a c a 11 a t a. t 541 tggc tcatgt C C 33 C 3 3 C cgccatg t tg acattgatta ttgactagtt a 11 a a t a g t a 601 atcaattacg gggtcattag ttcatagccc atatatggag ttccgcgtta cataacttac 661 ggtaaatggc ccgcc tag get gaccgcccaa cgacccccgc ccattgacgt caataatgac 721 gtatgttccc atagtaaege caatagggac tttccattga cgtcaatggg tggagtattt 781 acggtaaact gcccacttgg cagtaca tea agtgtatcat atgccaagta cgccccctat 841 tgacgtcaat gaeggtaaat ggcccgcctg gcattatgcc cagtacatga ccttatggga 901 ctttcctact tggcagtaca tetaegtatt agteateget a ttaccatgg tgatgcggtt 961 ttggcagtac atcaatgggc gtggatagcg gtttgactca cggggatttc caagtctcca 1021 ccccattgac gtcaatggga gtttgttttg gcaccaaaat caacgggact ttccaaaatg 1081 tcgtaacaac tccgccccat tgacgcaaat gggeggtagg cgtgtacggt gggaggteta 1141 tataagcaga gctctcccta tcagtga agatctccct atcagtgata gagategteg 1201 aegagetegt ttagtgaacc gtcagat etggagaege, catccacgct gttttgacct 1261 ccatagaaga caccgggacc gatccag ccgggtacca ccggtcttaa gatttccacc 1321 atgaaaccac catggccagc agcgacgcca accctagcga tggcagcgcc getaatetgg 1381 tgcccgaggt gaacaatgag gtgatggccc tggaacccgt ggtgggcgct gctatcgccg 1441 cccctgtggc cggacagcag aaegtgateg acccttggat ccgtaacaac ttegtgeagg1501 cccccggcgg cgagttcacc gtctccccta gaaacgcccc tggegagate ctgtggagcg 1561 c ccac gg ccctgatctg aacccc taco t agccacct ggccagaatg ac acggct 1621 acgccggagg atttgaggtg caagtgatcc tggccggcaa cgccttcacc gccggcaaag 1681 tgatcttcgc cgctgtgcct ccaaacttcc ctacagaggg cctgagccct cag t a 1741 ccatgttccc acacatcgtg gtcgacgtgc ggcagctgga acctgtgctc atccccctgc 1801 ctgacgtgcg gaacaacttc taccactaca accagagcaa cgaccccaca atcaagctga 1861 tcgccatgct gtacacccct ctgagggcca acaacgccgg egaegaegtg ttcactgttt 1921 cttgtcgtgt gctgaccaga ccttctcccg acttcgactt tatcttcctg gtgccaccta 1981 cagtggaaag cagaaccaag cctttcagcg tgcctgtcct gacagtggaa gagatgacca 2041 acagccggtt ccccatccct etggaaaage tgttcacggg cccttcttcc gcctttgtgg 2101 tgcagcctca gaatggcaga tgcac.aacag acggcgtgct gctgggcac.c. acccagctgt 2161 cccc t aa tatctgcacc ttccggggag atgtgacaca catcaccgga i-cca aaact a caeca t g a a cctggct gc cagaac gga acgact cga ccct accga gaa tccctg 2281 cccctctggg cacccctgac ttcgtgggca aaatccaggg cgtgctgacc cagaccaccc 2341 ggacc acgg ctc acaaga ggccac agg ccaccgta c ccgg tcc gc attttg 2401 ctcccaagct gggccgcgtg cagtttgaaa ccgacaccga tagagatttc gaggccaatc 2461 < c3c3C c3Cc3c3c3 gttc c cct gttggcg ga ttca gacgg cggcaccaca cac ga cg 2521 agccccaaca gtgggtgctg ccaagctaca gcggcagaaa cacccacaac gtgcacctgg 2581 cccccgctgt ggccccaaca ttccccggag aacagctgc t: gtttttcaga agcaccatgc 2641 ctggctgtag cggatatcct aacatggacc tggactgcct gctgcctcag gagtgggtgc 2701 agtactttta tcaggaggcc gcccccgccc a tctgatgt ggctctgc c agattc tga 2761 atcccgatac gggaagagtg ctgttc.gagt gcaagcttca taagagegge tacgtgaccg 2821 tggcccacac cggccagcac gatttggtca ttcctcctaa tggetaette agattcgaca 2881 gctgggtcaa ccagttctac acactggccc ctatgggcaa cggaacaggc cggcggagag 2941 ccgtgtaaat cgatcggcta gcgtaccggc ggccgcccta ttctatagtg tcacctaaat 3001 gctagagctc gctgatcagc ctcgactgtg ccttctagtt gccagccatc. tgttgtttgc 3061 ccctcccccg tgccttcctt gaccctggaa ggtgccactc ccactgtcct Lcctaataa 3121 aatgaggaaa ttgcatcgca ttgtctgagt aggtgtcatt ctattctggg gggtggggtg 3181 gggcaggaca ggattgggaa gacaatagca ggcatgctgg ggatgcggtg 3241 ggctctatgg cttctgaggc ggaaagaacc aaagcttacg cgttagttat taagcgatct 3301 gcatctcaat tagtcagcaa ccatagtccc gcccctaact ccgcccatcc cgcccctaac 3361 ccgc cc gt tccgcccatt ctccgcccca tcgctgact tttttttta t: t: tatgcaga 3421 ggccgaggcc gcctcggcct etgagetatt ccagaagtag tgaggagget tttttggagg 3481 cctaggcttt gcg ccgc tagag at: gggaaacga t: a ggctgaa c gatccg 3541 tattcagccc atatcgtttc tetagaaata aaatatcttt attttcatta catctgtgtg 3601 gg tttt gtgtgaatcg atagtac aa c tacgctct ccatctcga cc taagcttg 3661 tcgactcgaa gatctgggcg tggttaaggg tgggaaagaa tatataaggt gggggtctta 3721 tgtagttttg ta c tg tt gc ge ge eg ccgccgcca t: gagc cc c tcgtttgatg 3781 gaagcattgt gagctcatat ttgacaacgc gcatgccccc atgggccggg gtgcgtcaga 3841 atgtgatggg ctccagcatt gatggtegee ccgtcctgcc cgcaaactct actaccttga 3901 cctacgagac cgtgtctgga acgccgttgg agactgcagc ctccgccgc.c. gcttcagccg 3961 ctgcagccac cgcccgcggg attgtgactg actttgcttt cctgagcccg CLL- Cclcl Cci 4021 gtgcagcttc ccgttcatcc gcccgcgatg acaagttgac ggctcttttg gcacaattgg 4081 attctttgac ccgggaactt aatgtcgttt ctcagcagct gttggatctg cgccagcagg 4141 tttctgccct gaaggcttee tccc.c.tccca atgcggttta aaacataaat aaaaaaccag 4201 actctgtttg gatttggatc aagcaagtgt cttgctgtct ttatttaggg gttttgcgcg 4261 cgcggtaggc ccgggaccag eggteteggt cgttgagggt cctgtgtatt ttttc.c.agga 4321 cgtggtaaag gtgactctgg atgttcagat acatgggcat aagcccgtct ctggggtgga 4381 ggt gcacca c gcaga c teatgetgeg gggtggtgt t: g g tg tc cagtcgtagc 4441 aggagcgctg ggcgtggtgc ctaaaaa eg ctttcagtag caagctgatt gccaggggca 4501 ggccc gt gtaagtgttt acaaagcgg taagctggga tgggtgca a cgtggggata 4561 tgagatgcat cttggactgt atttttaggt tggctatgtt cccagccata tccctccggg 4621 gattcat tt g gcaga cc acc gc cag t tatccgg t: gcacttggga aa ttgtcat 4681 gtagcttaga aggaaatgcg tggaagaact tggagacgcc cttgtgacct ccaagatttt 4741 cca tgc tc gtccataatg atggca gg gccc cgggc ggc gcctgg gcgaag tat 4801 ttctgggatc actaacgtca tagttgtgtt ccaggatgag ategteatag gccattttta 4861 c a a a g c g c g g gcggagg t cc gac gcg gtataa gg t: cc tccggc ccaggggcgt4921 agttaccctc acagatttgc atttcccacg ctttgagttc agatgggggg atcatgtcta 498 cc gcggggc g tgaagaaa aeggtt txxx gggtagggga gatcagctgg gaag gc 5041 ggttcctgag cagctgcgac ttaccgcagc cggtgggccc gtaaatcaca cctattaccg 5101 gctgcaactg gtagttaaga gagetgeage tgccgtcatc cctgagcagg ggggccactt 5161 cgttaagcat gtccctgact cgcatgtttt ccctgaccaa atccgccaga aggcgctcgc 5221 cgcccagcga tagcagttct tgcaaggaag caaagttttt caacggtttg agaccgtccg 5281 ccgtaggcat gcttttgagc gtttgaccaa gcagttccag gcggtcccac ageteggtea 5341 cctgctctac ggcatctcga tccagcatat ctcctcgttt cgcgggttgg ggcggctttc 5401 gctgtacggc agtagtcggt gctcgtccag acgggccagg gtcatgtctt tccacgggcg 5461 cagggtcctc gtcagcgtag tctgggtcac ggtgaagggg tgcgctccgg gctgcgcgct 5521 ggccagggtg cgcttgaggc tggteetget ggtgetgaag cgctgccggt cttcgccctg 5581 cgcgtcggcc aggtagcatt tgaccatggt gtcatagtcc agcccctccg cggcgtggcc 5641 c t: ggcgcgc agcttgccct tggagg ggc gccgc cg g gggcagtgca gacttttg g 5701 ggcgtagagc ttgggcgcga gaaataccga ttccggggag taggcatccg cgccgcaggc 5761 cccgcagacg gtctcgc tt ccacgagcca g tgagctc ggccgttcgg ggtcaaaaac 5821 caggtttccc ccatgctttt tgatgcgttt cttacctctg gtttccatga gccggtgtcc 5881 acgc cggtg acg a gc tg txxxj tg e cccgtataca gaettgaga gcctgtcctc 5941 gagcggtgtt ccgcggtcct cctcgtatag aaactcggac cactctgaga caaaggctcg 6001 cgtccag cc agcacga gg agget gtg ggaggggtag cggtcgttgt ccactagggg 6061 gtccactcgc tccagggtgt gaagacacat gtcgccctct ccggcatcaa ggaaggtgat 6121 tgg tgt g gtgt ggcca cgtgaccggg tgttcctgaa ggggggctat aaaagggggt 6181 gggggcgcgt tcgtcctcac tctcttccgc ategetgtet gcgagggcca gctgttgggg 6241 tgagtactcc ctctgaaaag cgggcatgac ttetgegeta agattgtcag UUUCCddaaa 6301 cgaggaggat ttgatattca cctggcccgc ggtgatgcct ttgagggtgg ccgcatccat 6361 ctggtcagaa aagacaatct ttttgttgtc aagcttggtg gcaaacgacc cgtagagggc 6421 gttggacagc aacttggcga tggagcgcag ggtttggttt ttgtcgcgat cggcgcgctc 6481 cttggccgcg atgtttagct gcacgtattc gcgcgcaacg caccgccatt CC^C^C cicici o. C 6541 ggtggtgcgc tcgtcgggca ccaggtgcac gcgccaaccg cggttgtgca gggtgacaag 6601 gtcaacgctg gtggctacct ctccgcgtag gcgctcgttg gtccagcaga ggcggccgcc 6661 cttgcgcgag cagaatggcg gtagggggtc tagetgegte tcgtccgggg ggtetgegte 6721 cacggtaaag accccgggca gcaggcgcgc gtegaagtag tetatettge atccttgcaa 6781 g c tagcgcc tgctgccatg cgcgggcggc gcgcgcgc tcgtatgggt gagtggggg 6841 accccatggc atggggtggg tgagegegga ggcgtacatg C C Cj C o. o. o. tgt cgtaaacgta 6901 gaggggctct ctgag a ttc caagat tgt agggtagca t cttccaccgc gg tgctggc 6961 gcgcacgtaa tcgtatagtt cgtgcgaggg agegaggagg tcgggaccga ggttgctacg 7021 ggcgggctgc tctgctcgga agacta tx: txj cctgaagatg gcatgtgagt tgg tg tat 7081 ggttggacgc tggaagacgt tgaagctggc gtctgtgaga cctaccgcgt cacgcacgaa 7141 ggaggcgtag gagtcgcgca gcttgttgac cagctcggcg gtg cctgca cgtctagggc 7201 gcagtagtcc agggtttcct tgatgatgtc atacttatcc, tgtccctttt ttttccacag ‘7261 ctcgcggttg aggacaaact cttcgcggtc tttccagtac tettggateg gaaacccgtc 7321 ggcctccgaa cggtaagagc ctagcatgta gaactggttg acggcctggt aggcgcagca 7381 tcccttttct acgggtagcg cgtatgcctg cgcggccttc eggagegagg eg c gggt g 7441 cgcaaaggtg tccctgacca tgactttgag gtactggtat ttgaagtcag tgtegtegea 7501 tccgccctgc tcccag gca aaaagteegt gcgctttttg gaaegeggat ttggcagggc 7561 gaaggtgaca tcgttgaaga gtatctttcc cgcgcgaggc ataaagttgc gtgtgatgcg 7621 gaagggtccc ggcacctcgg aacggttgtt aa 11 CL cctgg geggegagea cgatctcgtc 7681 aaagccgttg atgttgtggc ccacaatgta aagttccaag aagcgcggga tgcccttgat 7741 ggaaggcaat tttttaagtt cctcgtaggt gagetettea ggggagctga gcccgtgctc 7801 tgaa g cc cagtc gcaa gatgagggtt ggaagcgacg a tgagctcc acaggtcacg 7861 ggccattagc atttgcaggt ggtcgcgaaa ggtcctaaac tggcgaccta tggccatttt 7921 t c ggggtg tgc gtaga aggtaagegg gtcttgttcc cagcggtccc a tccaaggtt 7981 cgcggctagg tctcgcgcgg cagtcactag aggctcatct ccgccgaact tcatgaccag 8041 catgaa gc a c gage get tccca ggc ccccatccaa g t t ggt ct ctacatcgta 8101 ggtgacaaag agaegetegg tgcgaggatg cgagccgatc gggaagaact ggatctcccg 8161 ccaccaattg gaggagt gc tattga tg g gtgaaagtag a tccctgc gaegggeega 8221 acactcgtgc tggcttttgt aaaaacgtgc gcagtactgg cagcggtgca cgggctgtac 8281 tcct cacg aggt gacct g cg ccgcg cacaaggaag c g gtggga atttgagccc8341 ctcgcctggc gggtttggct ggtggtcttc taettegget gettgteett gaccgtctgg 840 c tgc tcgagg ggagttacgg tggatcggac caeca egee g cgcgagccca aag ccaga 8461 gtccgcgcgc ggeggtegga gcttgatgac aacatcgcgc agatgggagc tgtccatggt 8521 ctggagctcc cgcggcgtca ggteaggegg gagctcctgc aggtttacct cgcatagacg 8581 ggtcagggcg egggetagat ccaggtgata cctaatttcc aggggctggt tggtggcggc 8641 gtcgatggct tgeaagagge cgcatccccg cggcgcgact acggtaccgc gcggcgggcg 8701 gtgggccgcg ggggtgtcct tggatgatgc atetaaaage ggtgaegegg gcgagccccc 8761 ggaggtaggg ggggctccgg acccgccggg agagggggca ggggcacgtc ggcgccgcgc 8821 gcgggcagga gctggtgctg egegegtagg ttgctggcga acgcgacgac gcggcggttg 8881 atctcctgaa tctggcgcct etgegtgaag acgacgggcc eggtgagett gaacctgaaa 8941 gagagttcga cagaatcaat ttcggtgtcg ttgaeggegg cctggcgcaa aatctcctgc 9001 acgtctcctg agttgtcttg ataggegate tcggccatga aetgetegat ctcttcctcc 9061 ggagatc c cgcgtccggc tcgctccacg gtggcggcg ggtcgttgga a a gcgggcc 9121 atgagctgcg agaaggegtt gaggcctccc tcgttccaga cgcggctgta gaccacgccc 9181 ccttcggca cgcgggcgcg catgaccacc egegaga t t g a g c t c c a c gtgccgggcg 9241 aagacggcgt agtttcgcag gegetgaaag aggtagttga gggtggtggc ggtgtgttct 9301 gccacgaaga ag c ac ccagcg tege aacg gg cgttgatatc ccccaaggcc 9361 tcaaggcgct ccatggcctc gtagaagtcc aeggegaagt tgaaaaactg ggagttgcgc 9421 gccg cacgg ttaac tcctc ctccagaaga eggatgage t cggcgacagt gtcgcgcacc 9481 tcgcgct C o. o. aggctacagg ggcctcttct tcttcttcaa tctcctcttc cataagggcc 9541 tccccttc t ettettetgg egg egg ggg ggagggggga c c gcggcg acgacggcgc 9601 accgggaggc ggtcgacaaa gcgctcgatc atctccccgc ggcgacggcg catggtctcg 9661 gtgacggcgc ggccgttctc gcgggggcgc agttggaaga cgccgcccgt catgtcccgg 9721 ttatgggttg gcggggggct gccatgcggc agggataegg egetaaegat gcatctcaac 9781 aattgttgtg taggtactcc gccgccgagg gacctgagcg agtccgcatc gaccggatcg 9841 gaaaacctct egagaaagge gtctaaccag tcacagtcgc aaggtagget gagcaccgtg 9901 gcgggcggca gcgggcggcg gtcggggttg tttctggcgg aggtgetget ga egatgtaa 9961 ttaaagtagg eggtettgag icggcggatg gtcgacagaa gcaccatgtc cttgggtccg 10021 gcctgctgaa tgcgcaggcg gtcggccatg ccccaggctt cgttttgaca tcggcgcagg 10081 tctttgtagt agtettgeat gageetttet accggcactt cttcttctcc ttcctcttgt 10141 cctgcatctc ttgeatetat cgctgcggcg geggeggagt ttggccgtag gtggcgccct 10201 c t: tcctccca tgcgtgtgac cccgaagccc ctcatcggct gaa cagggc agg eggeg 10261 acaacgcgct eggetaatat ggcctgctgc acctgcgtga gggtagactg gaagtcatcc 10321 atgtccacaa agcggtggta gcgcccg g ttgatggt t aag gcag ggccataacg 10381 gaccagttaa cggtctggtg acccggctgc gagagetegg tgtacctgag aegegagt O. O.10441 gccc tcgagt caa tacgta gtcgttgcaa gtccgcacc ggtactggta tcccaccaaa 10501 aagtgcggcg gcggctggcg gtagaggggc cagcgtaggg tggccggggc tccgggggcg 10561 agate tcca acataaggcg atgatateeg tagatgtacc ggaca cca ggtgatgeeg 10621 geggeggtgg tggaggcgcg eggaaagteg eggaegeggt tccagatgtt gcgcagcggc 10681 aaaaagtget ccatggtcgg gaegetetgg ccggtcaggc gcgcgcaatc gttgacgctc 10741 tagegtgeaa aaggagagee tgtaagcggg cactcttccg tggtctggtg gataaatteg 10801 caagggtatc atggcggacg accggggttc gagccccgta tccggccgtc cgccgtgatc 10861 catgcggtta ccgcccgcgt gtcgaaccca ggtgtgcgac gtcagacaac gggggagtgc 10921 tccttttggc ttccttccag gcgcggcggc tgetgegeta gcttttttgg ccactggccg 10981 cgcgcagcgt aagcggttag getggaaage, gaaagcatta agtggctcgc tccctgtagc 11041 cggagggtta ttttccaagg gttgagtege gggacccccg gttegagtet cggaccggcc 11101 ggaetgegge gaacgggggt ttgcctcccc gteatgeaag accccgcttg caaattcctc 11161 cggaaacagg gacgagcccc ttttttgctt ttcccagatg catccggtgc tgcggcagat 11221 gcgcccccct cct cage age ggc agagca agagcagcgg cagaca gca gggcaccctc 11281 ccctcctcct accgcgtcag gaggggcgac atccgcggtt gacgcggcag cagatggtga 11341 tacgaaccc ccgcggc cc gggcccggca ctacc gg c ttggaggagg gcgagggcc 11401 ggegeggeta ggagcgccct ctcctgagcg gcacccaagg gtgcagctga agcgtgatac 11461 gegtgaggeg tac tgeege ggc g cc gtttcgcgac egegaggg g aggagcccga 11521 ggagatgegg gategaaagt tccacgcagg gegegagetg cggcatggcc tgaategega 11581 gcggt gctg egegaggagg aetttgagee cgacgcgcga accgggatta g cccgcgcg 11641 cgcacacgtg gcggccgccg acctggtaac egeataegag cagacggtga accaggagat 11701 t actttcaa a a a a gc t t ta acaaccacgt gegtaeget t g ggcgcgcg aggagg ggc11761 tataggactg atgcatctgt gggact tgt aagcgcgctg gagcaaaacc caaatagcaa 11821 gccgctc tg gcgc gctgt tcac ta tagt gc gc cagc agggacaacg aggc ttcag 11881 ggatgcgctg ctaaacatag tagagcccga gggccgctgg ctgctcgatt tgataaacat 11941 C C LgC aga C atagtggtgc aggagcgcag cttgagcctg gctgacaagg tggccgccat 12001 caactattcc atgcttagcc tgggcaagtt ttacgcccgc, aagatatacc atacccctta 12061 cgttcccata gacaagg gg taaagatcga ggggttctac atgcgcatgg cgctgaaggt 12121 gcttaccttg agcgacgacc tgggcgttta tcgcaacgag cgcatccaca aggccgtgag 12181 cgtgagccgg cggcgcgagc tcagcgaccg cgagctgatg cacagcctgc12241 ggctggcacg ggcagcggcg atagagaggc cgagtcctac, tttgacgcgg gcgctgacct 12301 gcgctgggcc ccaagccgac gcgccctgga ggcagctggg gccggacctg ggctggcggt 12361 ggcacccgcg cgcgctggca acgtcggcgg cgtggaggaa tatgacgagg acgatgagta 12421 cgagcc gaq gacggcgagt actaagcggt gatgtttctg atcagatgat gcaagacqca 12481 cggacccgg cggtgcgggc ggcgc gcag agcc gccgt ccggcacttaa c ticcacggac 12541 gactggcgcc aggtcatgga ccgcatcatg tcgctgactg cgcgcaatcc tgacgcgttc 12601 cggc c gc cgcaggccaa ccggc ctcc gcaat ctgg a gcggtggt cccggcgcgc 12661 gcaaacccca cgcacgagaa ggtgctggcg atcgtaaacg cgctggccga aaacagggcc 12721 a ticcggcccg acgaggccgg cactgg c tac g cgcgc gc c gcgcgt ggctcgtt c 12781 aacagcggca acgtgcagac caacctggac cggctggtgg gggatgtgcg cgaggccgtg 12841 gcgc c tg agcgcgcgc gcagcagggc cactgggc t cc tggttgc ac aacgcx: 12901 t c c g a g t a cacagcccgc caacgtgccg cggggacagg aggactacac caactttgtg 12961 agcgc ctgc ggctaatggt gac gagac ccgc agtg aggtgtacca gtctgggcca 13021 gactattttt tccagaccag tagacaaggc, ctgcagaccg taaacctgag ccaggctttc 13081 aaaaacttgc aggggctgtg gggggtgcgg gctcccacag gcgaccgcgc gaccgtgtct 13141 agcttgctga cgcccaactc gcgcctgttg ctgctgctaa tagcgccctt cacggacagt 13201 ggcagcgtgt cccgggacac atacctaggt cacttgctga cactgtaccg cgaggccata 13261 ggtcaggcgc atgtggacga gcatactttc, caggagatta caagtgtcag ccgcgcgctg 13321 gggcaggaqq acacgggcag cctggaggca accctaaact acctgctgac caaccggcgg 13381 cagaagatcc cctcgttgca cagtttaaac agcgaggagg agcgcatttt gcgctacgtg 13441 cagcagagcg tgagccttaa cctgatgcgc gacggggtaa cgcccagcgt ggcgctggac 13501 atgaccgcgc gcaacatgga accgggcatg tatgcctcaa accggccgtt tatcaaccgc 13561 ctaatggact acttgcatcg cgcggccgcc gtgaaccccg agtatttcac caatgccatc 13621 tgaacccgc actggct cc gcxxxx: tggt ttctacaccg ggggattcga ggtgcccg g 13681 ggtaacgatg gattcctctg ggacgacata gacgacagcg tgttttcccc gcaaccgcag 13741 accct ctag ag gca ca gcgcg gc g gcagaggcgg cgctgcg ggaaagcttc 13801 c g c a g g c c a a gcagcttgtc cgatctaggc gctgcggccc cgcggtcaga tgctagtagc 13861 cca t: ttccaa gcttg t gg gtc c tacc agcactcgc ccacccgccc gcgcctgctg 13921 ggcgaggagg agtacctaaa caactcgctg ctgcagccgc agcgcgaaaa aaacctgcct 13981 ccggcat tc ccaacaacgg gatagagagc c agtggaca a g t gagt g ggaa acg 14041 tacgcgcagg agcacaggga cgtgccaggc ccgcgcccgc, ccacccgtcg tcaaaggcac 14101 gaccgtcagc ggggtctggt gtgggaggac gatgactcgg cagacgacag cagcgtcctg 14161 gatttgggag ggagtggcaa cccgtttgcg caccttcgcc ccaggctggg gagaatgttt 14221 taaaaaaaaa aaagcatgat gc aa L cl cl cl aaactcacca aggccatggc accgagcgtt 14281 ggttttcttg tattcccctt agtatgcggc gcgcggcgat gtatgaggaa ggtcctcctc 14341 cctcctacga gagtgtggtg agcgcggcgc cagtggcggc ggcgctgggt tctcccttcg 14401 atgctcccct ggacccgccg tttgtgcctc cgcggtacct gcggcctacc ggggggagaa 14461 acagcatccg ttactctgag ttggcacccc tattcgacac cacccgtgtg tacctggtgg 14521 acaacaagtc aacggatgtg gcatccctga actaccagaa cgaccacagc aactttctga 14581 ccacggtcat tcaaaacaat gactacagcc cgggggaggc aagcacacag accatcaatc 14641 ttgac accg g cgcactgg ggcggcg cc tgaaaacca t: cctgcatacc aacatgccaa 14701 a u g u g a a c g a gttcatgttt accaataagt ttaaggcgcg ggtgatggtg tcgcgcttgc 14761 c tiac tiaagga ca tcag t gagctgaaa t cg gtgggt gga ttcacg c tgcccgagg 14821 gcaactactc cgagaccatg accatagacc ttatgaacaa cgcgatcgtg gagcactact 14881 tgaaagtggg cagacagaac ggggt ctgg aaagcgaca t: cggggtaaag tt acacxx: 14941 gcaacttcag actggggttt gaccccgtca ctggtcttgt catgcctggg gtatatacaa 15001 acgaagcctt ccatccagac atca t tgc tgcc gg tg cggggtggac t tcacccaca 15061 gccgcctgag caacttgttg ggcatccgca agcggcaacc cttccaggag ggctttagga 15121 tcacct cga ga c tag g g ggtggtaaca txxxxjcac t: gttggatgtg g c cxr acx:15181 aggcgagctt gaaagatgac accgaacagg gcgggggtgg cgcaggcggc agcaacagca 15241 g ggcagcgg cgcgga gag aactccaacg cggc gccgc ggcaa gcag ccggtggagg 15301 acatgaacga tcatgccatt cgcggcgaca cctttgccac acgggctgag gagaagcgcg 15361 ctgaggccga agcagcggcc gaagctgccg cccccgctgc gcaacccgag g ucgagaacic 15421 ctcagaagaa accggtgatc aaacccctga cagaggacag caagaaacgc agttacaacc 15481 taataagcaa tgacagcacc ttcacccagt accgcagctg gtaccttgca tacaactacg 15541 gcgaccctca gaccggaatc cgctcatgga ccctgctttg cactcctgac gtaacctgcg 15601 gcucggagca ggtctactgg tcgttgccag acatgatgca agaccccgtg accttccgct 15661 ccacgcgcca gatcagcaac tttccggtgg tgggcgccga gctgttgccc gtgcactcca 15721 agagcttcta caacgaccag gccgtctact cccaactcat ccgccagttt acctctctga 15781 cccacgtgtt caatcgcttt cccgagaacc agattttggc gcgcccgcca gcccccacca 15841 tcaccaccgt cagtgaaaac gttcctgctc tcacagatca cgggacgcta ccgctgcgca 15901 acagc tcgg agg g ccag cgagtgacca tt c gacgc cagacgccgc acctgcccc 15961 acgtttacaa ggccctgggc atagtctcgc cgcgcgtcct atcgagccgc actttttgag 16021 caagcatg c catcc t t ta tcgccc gca a aacacagg ctggggcc g cgcttcccaa 16081 gcaagatgtt tggcggggcc aagaagcgct ccgaccaaca cccagtgcgc gtgcgcgggc 16141 ac taccgcgc gccctggggc gcgcacaaac gcggccgc c tgggcgcacc accgtcgatg 16201 acgccatcga cgcggtggtg gaggaggcgc gcaactacac gcccacgccg ccaccagtgt 16261 ccacagtgga cgcggcc tt cagaccgtgg gcgcggagc ccggcgc t g c t a a a a t q a 16321 agagacggcg gaggcgcgta gcacgtcgcc accgccgccg acccggcact g c c g c c c a a c 16381 gcgcggcggc ggccc gc aaccgcgcac gtcgc ccgg ccgacgggcg gcc tgcggg 16441 ccgctcgaag gctggccgcg ggtattgtca ctgtgccccc caggtccagg cgacgagcgg 16501 ccgccgcagc agccgcggcc attagtgcta tgactcaggg tcgcaggggc aacgtgtatt 16561 gggtgcgcga ctcggttagc ggcctgcgcg tgcccgtgcg cacccgcccc ccgcgcaact 16621 agattgcaag aaaa ac c ttagactcgt actgttgtat gtatccagcg gcggcggcgc 16681 gcaacgaagc tatgtccaag c g c a a a a c a aagaagagat gctccaggtc atcgcgccgg 16741 agatctatgg ccccccgaag aaggaagagc aggattacaa gccccgaaag ctaaagcggg 16801 tcaaaaagaa a a a g si 5i 5i oj at gatgatgatg aacttgacga cgaggtggaa ctgctgcacg 16861 ctaccgcgcc caggcgacgg gtacagtgga aaggtcgacg cgtaaaacgt gttttgcgac 16921 ccggcaccac cgtagtcttt acgcccggtg agcgctccac ccgcacctac aagcgcgtgt 16981 a ga gagqt gtacggcgac gaggacctgc ttgagcaggc caacgagcgc ctcggggagt 17041 tgcct cgg aaagcggca aaggaca tgc tggcg gcc gctggacgag ggcaacccaa 17101 cacctagcct aaagccc g acactgcagc aggtgctgcc cgcgcttgca ccgtccgaag 17161 aagcgcgg cctaaagcgc gagtctggtg ac tggcacc c ccg gc g ctgatggtac 17221 ccaagcgcca gcgactggaa gatgtcttgg a a a. a. a. a t q a c cgtggaacct gggctggagc 17281 ccgaggtccg cg gcggccsi a caagcagg tggcgccggg actgggcgtg cagaccgtgg 17341 acgttcagat acccactacc agtagcacca gtattgccac cgccacagag ggcatggaga 17401 cacaaacgtc cccggt tgcc tcagcggtgg cgga gccgc ggtgcaggcg gtcgctgcgg 17461 ccgcgtccaa gacctctacg g iggtgcaaa cggacccgtg gatgtttcgc gtttcagccc 17521 cccggcgccc gcgccgttcg aggaagtacg gcgccgccag cgcgctactg cccgaatatg 17581 ccctacatcc ttccattgcg cctacccccg gctatcgtgg ctacacctac cgccccagaa 17641 gacgagcaac tacccgacgc cgaaccacca ctggaacccg ccgccgccgt cgccgtcgcc 17701 agcccgtgct ggccccgatt tccgtgcgca gggtggctcg cgaaggaggc aggaccctgg 1 1761 tgctgccaac agcgcgctac caccccagca tcgtttaaaa gccggtcttt gtggttcttg 17821 cagatatggc cctcacctgc cgcctccgtt tcccggtgcc gggattccga ggaagaatgc 17881 accg uaggaci gggcatggcc ggccacggcc tgacgggcgg catgcgtcgt gcgcaccacc 17941 ggcggcggcg cgcgtcgcac cgtcgcatgc gcggcggtat cctgcccctc cttattccac 18001 tgatcgccgc ggcgattggc gccgtgcccg gaattgcatc cgtggccttg caggcgcaga 18061 gacact att a a a a a c a a g t tgcatgtgga a a a a t ca a a a taaaaagtct ggactc cac 18121 gctcgcttgg tcctgtaact attttgtaga atggaagaca tcaactttgc gtctctggcc 18181 ccgcgac cg gc cgcgccc g catggga a c ggca g tatcggcac cagca tg 18241 agcggtggcg ccttcagctg gggctcgctg tggagcggca ttaa a a a ttt cggttccacc 18301 gttaagaact atggcagcaa ggcctggaac agcagcacag gcc g tgct gagggataag 18361 ttgaaagagc ci acaaaagg u g gtagatggcc tggcctctgg cattagcggg 18421 g tggtgg cc tggccaacca ggcagtgcaa a aagat acag aagct ga ccccgc 18481 cctcccgtag aggagcctcc accggccgtg gagacagtgt ctccagaggg gcgtggcgaa 18541 gc tccgc gccccgacag gg g act c gg gacgc aa t gacga gcc ccc cg18601 tacgaggagg cactaaagca aggcctgccc accacccgtc ccatcgcgcc catggctacc 18661 ggagtgctgg gccagcacac acccgtaacg ctgg cc gc ctccccccgc cgacacccag 18721 cagaaacctg tgctgccagg cccgaccgcc gttgttgtaa cccgtcctag ccgcgcgtcc 18 81 ctgcgccgcg ccgccagcgg tccgcgatcg ttgcggcccg tagccagtgg caactggcaa 18841 agcacactga acagcatcgt gggtctgggg gtgcaatccc tgaagegeeg aegatgette 18901 tgatagctaa cgtgtcgtat gtgtgtcatg tatgcgtcca tgtcgccgcc agaggagetg 18961 ctgagccgcc gcgcgcccgc tttccaagat ggctacccct tegatgatge egeagtggte 19021 t eacatgcac atctcgggcc aggacgcctc ggagtacctg agccccgggc tggtgcagtt 19081 tgcccgcgcc accgagacgt acttcagcct gaataacaag tttagaaacc ccacggtggc 19141 gcctacgcac gacgtgacca cagaccggtc ccagcgtttg aegetgeggt tcatccctgt 19201 ggaccgtgag gataetgegt actcgtacaa ggcgcggttc accctagctg tgggtgataa 19261 ccgtgtgctg gacatggctt ccacgtactt tgacatccgc ggcgtgctgg 3C3 CCC 19321 tac t: tttaag ccctactctg gcactgcc t c cgccc g gc cccaagg g gccccaaa 19381 tccttgcgaa tgggatgaag ctgctactgc tettgaaata aacctagaag aagaggaega 19441 tgac c aa gaegaagt g acgagc agc tgagcagcaa aaaactcacg ta tgggca 19501 ggcgccttat tetggtataa atattacaaa ggagggtatt caaataggtg tegaaggtea 19561 a a c a c c t a a a tatgeegata aaacat t: tea acctgaacct: caaataggag a tctcagtg 19621 gtacgaaaca g a a a c a a t atgeagetgg gagagtccta aaaaagacta ccccaatgaa 19681 accat ttac ggttca t tg ca acccac a a a t q a a a a t ggagggc g gc c g 19741 s a a cf c s s c o. o. aatggaaagc tagaaag tea agtggaaatg caatttttct caactactga 19801 ggcagccgca ggc tg t ata ac tgac tcctaaagtg g a g aca gtgaag gt 19861 agatatagaa accccagaca ctcatatttc, ttacatgccc actattaagg aaggtaactc 19921 acgagaacta atgggccaac aatetatgee caacaggcct aattacattg c c ettaggga 19981 caattttatt ggtctaatgt attacaacag cacgggtaat atgggtgttc tggcgggcca 20041 agcatcgcag ttgaatgctg ttgtagattt gcaagacaga aacacagagc tttcatacca 20101 gcttttgctt gattccattg gtgatagaac caggtacttt tctatgtgga atcaggctgt 20161 tgacagctat gatccagatg ttagaattat tgaaaatcae ggaaetgaag atgaacttcc 20221 aaattactgc tttcc.ac.tgg gaggtgtgat taatacagag actcttacca aggtaaaacc 20281 taaaacaggt caggaaaatg gatgggaaaa agatgctaca gaattttcag ataaaaatga 20341 aataagagtt ggaaataatt ttgccatgga aatcaatcta aatgccaacc tgtggagaaai 20401 tttcctgtac tccaacatag cgctgtattt gcccgacaag ctaaagtaca gtccttccaa 20461 cgtaaaa t tctgataacc: caaacacc t cgactacatg aca agegag tggtggc cc 20521 cgggctagtg gactgctaca ttaaccttgg ageaegetgg tcccttgact atatggacaa 20581 cgtcaaccca tttaaccacc accgcaatgc ggee tgege t ccgc c a tg gc ggg 20641 caatggtcgc tatgtgccct tccacatcca ggtgcctcag aagttctttg ccattaa a a a 20701 cc tccttc c ctgccgggct catacacc ta cgag gga c caggaagg a tgttaacat 20761 ggttctgcag agctccctag gaaatgacct aagggttgac ggagccagca ttaagtttga 20821 t gc tttgc ctttacgcca cc c txxx: ca ggcccac aacaccgcct cc cgc ga 20881 ggccatgctt agaaacgaca ccaacgacca gtcctttaac gactatctct ccgccgccaa 20941 catgctctac cctatacccg ccaacgctac caacgtgccc atatcc CL tee cctcccgcaa 21001 ctgggcggct ttccgcggct gggccttcac, gegeettaag actaaggaaa ccccatcact 21061 gggctcgggc tacgaccctt attacaccta ctctggctct ataccctacc eagatggaac 21121 cttttacctc aaccacacct ttaagaaggt ggccattacc tttgactctt ctgtcagctg 21181 gcctggcaat gaccgcctgc ttacccccaa cgagtttgaa a tta CL geget cagttgacgg 21241 ggagggttac aacgttgccc agtgtaacat gaccaaagac tggttcctgg tacaaatgct 21301 age caactat aacattggct accagggctt ct CL t CL tccca gagagctaca aggaccgcat 21361 gtactccttc tttagaaact tccagcccat gageegteag gtggtggatg atactaaata 21421 caaggactac caacaggtgg gcatcctaca ccaacacaac aactctggat ttgttggcta 21481 ccttgcccxx: a ex: a tgcgcg aaggac ggc c accctgc t aacttcccct atccgc at 21541 aggcaagacc gcagttgaca gcattaccca ga aaa agt t c etttgegate gcaccctttg 21601 gcgcatccca ttctccagta ac tta tgte c gggcgc c cacagacc tgggcc aa 21661 ccttctctac gccaactccg cccacgcgct agacatgact tttgaggtgg atcccatgga 21721 cgagcccacc ette t: t: t tg ttttgtttga ag e ttgac gtgg ccg g gc cc gcc 21781 gcaccgcggc gtcatcgaaa ccgtgtacct gcgcacgccc ttctcggccg gcaacgccac 21841 a a c a 11 a a a g a agcaagcaac a tea a caaca ge gee gee tgggctccag tgagc gg 21901 ctgaaagcca ttgtcaaaga tcttggttgt gggccatatt ttttgggcac ctatgacaag 21961 cgc ccag gett tgtttc tccacacaag c cgcctgcg ccatagtcaa eggeegg22021 cgcgagactg ggggcgtaca ctggatggcc tttgcctgga acccgcactc aaaaacatgc 22081 tacc tctttg agccctttgg cttttc gac cagcgactca agcaggttta ccagtttgag 22141 tacgagtcac tcctgcgccg tagcgccatt gcttcttccc ccgaccgctg tataaegetg 22201 gaaaagtcca cccaaagcgt acaggggccc aactcggccg cctgtggact attetgetge 22261 atgtttctcc acgcctttgc caactggccc caaactccca tggatcacaa ccccaccatg 22321 aaccttatta ccggggtacc caactccatg ctcaacagtc cccaggtaca gcccaccctg 22381 cgtcgcaacc aggaacagct ctacagcttc ctggagcgcc actcgcccta cttccgcagc 22441 cacagtgcgc agattaggag cgccacttct ttttgtcact tgaaaaacat g uaaaaat 0.0.22501 tgtactagag acactttcaa taaaggcaaa tgcttttatt tgtacactct egggtgatta 22561 tttaccccca cccttgccgt ctgcgccgtt taaaaatcaa aggggttctg ccgcgcatcg 22621 ctatgcgcca ctggcaggga cacgttgcga tactggtgtt tagtgctcca cttaaactca 22681 ggcacaacca tccgcggcag ctcggtgaag ttttcactcc acaggctgcg caccatcacc 22741 aacgcgttta gcaggtc gg cgccga c ttga gtcgc agttggggcc ccgccctgc 22801 gcgcgcgagt tgcgatacac agggttgcag cactggaaca ctatcagcgc cgggtggtgc 22861 acgctggcca gcacgc ett gtcgg g tc agatccgcg t: ccaggtcctc cgcgttgctc 22921 agggcgaacg gagteaaett tggtagctgc cttcccaaaa agggcgcgtg cccaggcttt 22981 gag gc ct cgc ccgtag tggcatcaaa aggtgaccgt gcccggtctg ggcgttagga 23041 tacagcgcct gcataaaagc cttgatctgc ttaaaagcca cctgagcctt tgcgccttca 23101 gaga a ca tgccgca ga cttgccgg aactgattgg ccggacaggc cgcgtc tgc 23161 acgcagcacc ttgcgtcggt gttggagatc tgcaccacat ttcggcccca ccggttcttc 23221 acga tcttgg ccttgctaga ctgctcc t: c agcgcgcgct gcccgttttc gc cgtc ca 23281 tccatttcaa tcacgtgctc cttatttatc, ataatgcttc cgtgtagaca ettaageteg 23341 ccttcgatct cagcgcagcg gtgcagccac aacgcgcagc ccgtgggctc gtgatgcttg 23401 taggtcacct etgeaaaega ctgcaggtac gcctgcagga atcgccccat catcgtcaca 23461 aaggtcttgt tgctggtgaa ggtcagctgc aacccgcggt gctcctcgtt cagccaggtc 23521 ttgcatacgg ccgccagagc ttccacttgg tcaggcagta gtttgaagtt egeetttaga 23581 tcgttatcca cgtggtactt gtccatcagc gcgcgcgcag cctccatgcc cttctcccac 23641 gcagacacga tcggcacact cagcgggttc atcaccgtaa tttcactttc cgcttcgctg 23701 ggctcttcct cttcctcttg cgtccgcata ccacgcgcca ctgggtcgtc ttcattcagc 23761 cgccgcactg tgcgcttacc tcctttgcca tgcttgatta gcaccggtgg gttgctgaaa 23821 cccaccattt gtagcgccac atcttctctt tcttcctcgc tgtccacgat tacctctggt 23881 g ggcgggc getegggett gggagaaggg cgcttctttt tcttcttggg cgc tggcc 23941 aaatccgccg ccgaggtcga tggccgcggg ctgggtgtgc gcggcaccag egegtettgt 24001 gatgagtctt cctcg cctc ggactcgata cgccgcctca tccgcttttt tgggggcgcc 24061 cggggaggcg geggegaegg ggacggggac gacacgtcct ccatggttgg gggaegtege 24121 gccgc ccgc gtccgcgctc gggggtgg t: tcgcgctgct cctcttcccg ac ggccatt 24181 tccttctcct ataggcagaa aaagatcatg gagtcagtcg agaagaagga cagcctaacc 24241 gccccctctg agttcgccac caccgcctcc accgatgccg ccaacgcgcc taccaccttc 24301 cccgtcgagg cacccccgct tgaggaggag gaagtgatta tcgagcagga cccaggtttt 24361 gtaagcgaag aegaegagga ccgctcagta ccaacagagg ataaaaagca agaccaggac 24421 aacgcagagg caaacgagga acaagtcggg cggggggacg aaaggcatgg cgactaccta 24481 gatgtgggag aegaegtget gttgaagcat ctgcagcgcc agtgcgccat tatctgcgac 24541 gcgttgcaag agcgcagcga tgtgcccctc gccatagcgg atgtcagcct tgcctacgaa 24601 cgccacctat tctcaccgcg cgtacccccc aaacgccaag aaaacggcac atgcgagccc 24661 aacccgcgcc teaaetteta ccccgtattt gccgtgccag aggtgettge cacctatcac 24721 atctttttcc aaaactgcaa gataccccta tcctgccgtg ccaaccgcag ccgagcggac 24781 aagcagctgg ccttgcggca gggcgctgtc atacctgata tcgcctcgct caacgaagtg 24841 ccaaaaatct ttgagggtct tggacgcgac gagaagcgcg cggcaaacgc tctgcaacag 24901 gaaa ca cg aaaa ga aag tcactctgga gtgttggtgg a ctcgaggg tg caacgcg 24961 cgcctagccg tactaaaacg cagcatcgag gtcacccact ttgcctaccc ggcacttaac 25021 c tacccccca aggte t ag cacagtca t:g agtg gctga tc tgcgccg gcgcagccc 25081 ctggagaggg atgeaaattt gcaagaacaa acagaggagg gcctacccgc agttggcgac 25141 gagcagctag egege gget tcaaacgcgc gagcctgccg aettgg gga gcgacgcaaa 25201 ctaatgatgg ccgcagtgct cgttaccgtg gagcttgagt gcatgcagcg gttctttgct 25261 gacccgg ga tgc gcgcaa gctagagga acattgcact acacctttcg acagggctac 25321 gtacgccagg cctgcaagat ctccaacgtg gagctctgca acctggtctc ctaccttgga 25381 tttt cacg aaaaccgcct tgggc aac t get ea ccacgctc a gggcgaggcg25441 cgccgcgact acgtccgcga ctgcgtttac ttatttctat gctacacctg gcagacggcc 2550 a tgggcg tt ggcagcagtg ettggaggag tgcaacctca aggagetgea gaa e get 25561 aagcaaaact tgaaggacct atggaeggee ttcaacgagc gctccgtggc cgcgcacctg 25621 gcggacatca ttttccccga acgcctgctt aaaaccctgc aacagggtct gccagacttc 25681 accagtcaaa gcatgttgca gaaetttagg aactttatcc, tagagcgctc aggaatettg 25741 cccgccacct gctgtgcact tcctagcgac tttgtgccca ttaagtaeeg cgaatgccct 25801 ccgccgcttt ggggccactg ctaccttctg cagctagcca actaccttgc ctaccactct 25861 gaca uaatgg aagacgtgag eggtgaeggt etaetggagt gtcactgtcg ctgcaaccta 25921 tgcaccccgc accgctccct ggtttgcaat tcgcagctgc, ttaaegaaag tcaaattatc 25981 ggtacctttg age t gca ggg tccctcgcct gaegaaaagt ccgcggctcc ggggttgaaa 26041 ctcactccgg ggctgtggac gtcggcttac cttcgcaaat ttgtacctga ggactaccac 26101 gCCC C aCfa ttaggttcta cgaagaccaa tcccgcccgc etaatgegga gcttaccgcc 26161 tgcgtc ta ccc gggcca cattct ggc caattgcaag ccatcaacaa agcccgccaa 26221 gagtttctgc taegaaaggg acggggggtt tacttggacc cccagtccgg cgaggagctc 26281 aacccaatcc ccccgccgcc gcagccctat c gcagcagc cgcgggccct tgcttcccag 26341 gatggcaccc aaaaagaagc tgcagctgcc gccgccaccc aeggaegagg aggaatactg 26401 ggacagtcag gcagaggagg ttttggacga gg gg gg g gac tgatgg aagac ggga 26461 gagcctagac gaggaagett ccgaggtcga agaggtgtea gacgaaacac cgtcaccctc 26521 ggtcgcattc ccctcgccgg cgcccc gaa at egg ca ace gg ccagca tggctacaac 26581 ctccgctcct caggcgccgc cggcactgcc cgttcgccga cccaaccgta gatgggacac 26641 cac tgga cc agggccg t agtccaagca gccgccgccg tt cccaa agc ac ca 2670 gcgccaaggc taccgctcat ggcgcgggca caagaacgcc atagttgett gettgeaaga 26761 ctgtgggggc aacatctcct tcgcccgccg ctttcttctc taccatcacg gegtggeett 26821 cccccgtaac atcctgcatt actaccgtca tctctacagc, ccatactgca ccggcggcag 26881 cggcagcaac agcagcggcc acacagaagc aaaggcgacc ggatagcaag actctgacaa 26941 agcccaagaa atccacagcg gcggcagcag caggaggagg agegetgegt ctggcgccca 27001 acgaacccgt atcgacccgc gagettagaa acaggatttt tcccactctg..a ugetatat 27061 ttcaacagag caggggccaa gaacaagagc tgaaaataaa aaacaggtct ctgcgatccc 27121 tcacccgcag etgeetgtat cacaaaagcg aagatcagct tcggcgcacg ctggaagacg 27181 cggaggctct cttcagtaaa tactgcgcgc tgactcttaa ggactagttt cgcgcccttt 27241 ctcaaattta agegegaaaa ctacgtcatc tccagcggcc acacccggcg ccagcacctg 27301 t tgteagege catt tgagc aaggaaa t tc ccacgcccta cat tggagt ac cage cac 27361 aaatgggact tgcggctgga gctgcccaag actactcaac ccgaat a a a c tacatgagcg 27421 cgggacccca catga ta cc cgggtc acg gaataegege ccaccga c cgaattctcc 27481 tggaacaggc ggctattacc accacacctc gtaataacct taatccccgt agttggcccg 27541 c tgccc ggt gt ccaggaa agtcccgc tc ccaccactgt ggtacttccc agagacgccc 27601 aggeegaagt tcagatgact aactcagggg cgcagcttgc gggcggcttt cgtcacaggg 27661 tgcggtcgcc cgggcaggg ataactcacc tgacaatcag agggcgaggt att cage tea 27721 aegaegagte ggtgagctcc tegettggte tccgtccgga cgggacattt cagatcggcg 27781 gcgccggccg ctcttcattc acgcctcgtc aggcaatcct aactctgcag acctcgtcct 27841 ctgagccgcg ctctggaggc attggaactc tgcaatttat tgaggagttt gtgccatcgg 27901 tetaettt aa ccccttctcg ggacctcccg gccactatcc ggatcaattt attcctaact 27961 ttgacgcggt aaaggactcg geggaegget aegaetgaat gttaagtgga gaggcagagc 28021 aactgcgcct gaaacacctg gtccactgtc gccgccacaa gtgctttgcc cgcgactccg 28081 gtgagttttg ctactttgaa ttgcccgagg atcatatcga gggcccggcg cacggcgtcc 28141 ggcttaccgc ccagggagag cttgcccgta geetgatteg ggagtttacc cagcgccccc 28201 tgctagttga gcgggacagg ggaccctgtg ttctcactgt gatttgcaac tgtcctaacc 28261 ctggattaca tcaagatcct ct a gttaatg tcaggtcgcc caagtegatt aactagagta 28321 cccgggg tc ttat tccc taactaataa a a a a a a a t a a t a gc tca ett ettaaa 28381 atcagttagc aaatttctgt ccagtttatt cagcagcacc tccttgccct cctcccagct 28441 c tggtattgc age t tee tee tggctgcaaa c ttctccac aatctaaatg gaa gteagt 28501 ttcctcctgt tcctgtccat ccgcacccac tatcttcatg ttgttgcaga tgaagegege 28561 aagaccgtct gaaga acc tc ccccgt gtatccata gac cgg a ccg tcctcc 28621 aactgtgcct tttcttactc ctccctttgt atcccccaat gggtttcaag agagtccccc 28681 tgggg ctc tctttgc cc tatccgaacc tctagttacc tccaatggca ge geget 28741 caaaatgggc aacggcctct ctctggacga ggccggcaac cttacctccc aaaatgtaac 28801 cactgtgagc ccacc e ea aaaaaaccaa gtcaaacata aacctggaaa tatctgcacc28861 cctcacagtt acctcagaag C C C t a a C eg ggctgccgcc gcacctctaa tggtcgcggg 2892 caacacactc acc tgcaat cacaggcccc gct ccgtg cacgactcca aacttagcat 28981 tgccacccaa ggacccctca cagtgtcaga aggaaageta gccctgcaaa catcaggccc 29041 cctcaccacc accgatagca gtacccttac tatc etge tcaccccctc taactactgc 29101 cactggtagc ttgggcattg aettgaaaga gcccattta acacaaaatg gaaaactagg 29161 actaaagtac ggggctcctt tgcatgtaac agacgaccta aacactttga ccgtagcaac 29221 tggtccaggt gtgactatta ataataette cttgcaaact aaagttactg gagccttggg 29281 ttttgattca caaggcaata tgeaaettaa tgtagcagga ggactaagga ttgattetea 29341 aaacagacgc ettataettg atgttagtta tccgtttgat gctcaaaacc aactaaatct 29401 aagactagga cagggccctc tttttataaa ctcagcccac aacttggata ttaactacaa 29461 caaaggcctt tacttgttta cagcttcaaa caattccaaa aagettgagg ttaacctaag 29521 cactgccaag gggttgatgt ttgacgctac agccatagcc attaatgeag gagatgggct 29581 tga ttggt tcacctaatg caccaaacac aaatcccctc Hddd ggcc tgg 29641 cctagaattt gattcaaaca aggctatggt tcctaaacta ggaactggcc ttagttttga 29701 c gc ca gt gee a tacag t gga caa a a a t a a t g a t aagetaaett tgtggaccac 29761 accagctcca tctcctaact gtagactaaa tgcagagaaa gatgctaaac tcactttggt 29821 C C 11 d d Cl d d d d tgtggcagtc aaatac t: tgc tacagtttca gttttggctg a aggcag 29881 tttggctcca atatctggaa cagttcaaag tgctcatctt attataagat ttgacgaaaa 29941 tggagtgcta c t a a a c a a 11 ccttcctgga cccagaata t tggaacttta gaaatggaga 30001 tcttactg d.d. ggcacagcct atacaaacgc tgttggattt atgcctaacc a ucagctta 30061 tccaaaatct C d C CZJ Cf d d d d ctgccaaaag t c ttgtc agtcaagttt ac t a egg 30121 agacaaaact aaacctgtaa cactaaccat tacactaaac ggtacacagg aaacaggaga 30181 cacaactcca agtgcatact etatgteatt ttcatgggac tggtctggcc acaactacat 30241 taatgaaata tttgccacat cctcttacac tttttcatac attgcccaag aataaagaat 30301 cgtttgtgtt atgtttcaac gtgtttattt ttcaattgc 0a c gaaaatttca agtcattttt 30361 cattcagtag tatagcccca - - C* C* d C d gcttatacag atcaccgtac cttaatcaaa 30421 C LCdCdC ddC cctagtattc aacctgccac ctccctccca acacacagag tacacagtcc 30481 tttctccccg getggeetta aaaagcatca tatcatgggt aacagacata ttcttaggtg 30541 ttatattcca cacggtttcc tgtcgagcca aacgctcatc agtgatatta ataaactccc 30601 cgggcagctc aettaagtte atgtcgctgt ccagctgctg agccacaggc tgctgtccaa 30661 cttgcggttg ettaaeggge ggegaaggag aagtccacgc ctacatgggg gtagagteat 30721 a a tcgtgcat cagg t gg eggtgg gc t: gc gc gcgc gcgaataaac get ee gee 30781 gccgctccgt cctgcaggaa tacaacatgg cagtggtctc ctcagcgatg attcgcaccg 30841 c cage age at aaggegeett gtcctccggg cacagcagcg caccctgatc teaettaaat 30901 cagcacagta actgcagcac agcaccacaa tattgttcaa aatcccacag tgeaaggege 30961 tg a tccaaa gctcatggcg gggaccacag a ccc cgtg gccatcatac cac agcgca 31021 ggtagattaa gtggcgaccc ctcataaaca cgctggacat aaacattacc tcttttggca 31081 tgttgtaatt caccacctcc cggt cc t taaacctctg attaaacatg gcgccatcca 31141 ccaccatcct aaaccagctg gccaaaacct gcccgccggc tatacactgc agggaaccgg 31201 gactggaaca atgacagtgg agagcccagg actcgtaacc atggatcatc atgetegtea 31261 tgatatcaat gttggcacaa cacaggcaca cgtgcataca cttcctcagg attacaagct 31321 cctcccgcgt tagaaccata tcccagggaa caacccattc ctgaatcagc gtaaatccca 31381 cactgcaggg aagacctcgc acgtaactca cgttgtgcat tgtcaaagtg ttacattcgg 31441 gcagcagcgg atgatcctcc agtatggtag cgcgggtttc tgtctcaaaa ggaggtagac 31501 gatccctact gtacggagtg cgccgagaca accgagatcg tgttggtcgt agtgtcatgc 31561 Cdddl-CJCJddC geeggaegta gtcatatttc ctgaagcaaa accaggtgcg ggcgtgacaa 31621 acagatctgc gtctccggtc tcgccgctta gategetetg tgtagtagtt gtagtatatc 31681 cactctctca aagcatccag gcgccccctg gcttcgggtt ctatgtaaac tccttcatgc 31741 gc:c:gc:t ccc tgataac tc caccaccgca gaataagcca cacccagcca acctacacat 31801 tcgttctgcg agtcacacac gggaggagcg ggaagagctg gaagaaccat gttttttttt 31861 t t: tccaaa agattatcca aaacctcaaa tg gatet ttaagtgaa cgcgctcccc 31921 tccggtggcg tggtcaaact ctacagccaa agaacagata atggcatttg taagatgttg 31981 c ca t ct tccaaaa gc aaacggccct cacgtccaag tggacgtaaa ggctaaaccc 32041 ttcagggtga atctcctcta taaacattcc agcaccttca accatgccca aataattctc 32101 a tc tcgccac cttctcaata tat etc aag caaatcccga tat taag tc cggcc ttgt 32161 aaaaatctgc tccagagcgc cctccacctt cagcctcaag cagcgaatca tgattgcaaa 32221 aattcag tt cctcaca ac etgtat aga ttcaaaagcg gaacattaac aa aataeeg32281 cgatcccgta ggtcccttcg cagggccagc t g a. a. cataat cgtgcaggtc tgcacggacc 32341 agcgcggcc cttccxxr cx: aggaacca t:g acaaaagaac cx:acactgat gac cgc 32401 atactcggag ctatgctaac cagcgtagcc, ccgatgtaag cttgttgcat gggcggcgat 32461 a uaaaatgca aggtgctgct CSSdddcl LCcl ggcaaagcct cgcgcaaaaa dgddd CdCd 32521 tcgtagtcat gctcatgcag ataaaggcag gtaagctccg gaaccaccac agaaaaagac 32581 accatttttc tctcaaacat gtctgcgggt ttctgcataa acacaaaata aaataacaaa 32641 a 51515* attt cl aacattagaa gcctgtctta caacaggaaa aacaaccctt ataagcataa 32701 gacggactac ggccatgccg gcgtgaccgt aaaaaaactg gtcaccgtga UUdddddCfCd 32761 ccaccgacag ctcctcggtc atgtccggag tcataatgta agactcggta aacacatcag 32821 gttgattcac tcggtcagtg ctaaaaagcg accgaaatag cccgggggaa tacatacccg 32881 caggcgtaga gacaacatta cagcccccat aggaggtata acaaaattaa taggagagaa 32941 aaacacataa acacctgaaa aaccctcctg cctaggcaaa atagcaccct cccgctccag 33001 aacaac tac agcgcttxx:a cagcggcagc cataacagtc a cx:ttacx:a g aaaaaaga 33061 aaacctatta aaaaaacdcc actcgacacg gcaccagctc aatcagtcac agtgtaaaaa 33121 gggcca gt gcagagcgag tatatatagg a c t a a a a a a t gacgt acgg tt:aaagtxx:a 33181 caaaaaacac ccagaaaacc gcacgcgaac ctacgcccag aaacgaaagc caaaaaaccc 33241 acaacttcct caa tcgtcsi cttcxxj t: t: t: t: cccacgttac gtcacttcxx: a t: tttaagaa 33301 aactacaatt cccaacacat acaagttact ccgccctaaa acctacgtca cccgccccgt 33361 tcxxr cgcxx: cgcgccacg cacaaactcc accccctca t: tatcatattg gcttca tcx: 33421 aaaataaggt atattattga tgatgSEQ ID NO: 25: rAd-ED150_CMV (TetO) -GI.1_VP1_SV40 -dsRNA nucleotide sequence 1 catcatcaat aatatacctt attttggatt gaagccaata tgataatgag ggggtggagt 61 ttgtgacgtg gcgcggggcg tgggaacggg gcgggtgacg tagtag tgtg gcggaagtgt 121 gatgttgcaa gtgtggcgga acacatgtaa gcgacggatg tggcaaaagt gacgtttttg 181 gtgtgcgcxxj gtgtacacag gaagtgacaa ttttcgcgcg g ttaggcg gatgttgtag 241 taaatttggg cgtaaccgag taagatttgg ccattttcgc gggaaaactg aataagagga 301 agtgaaatct gaataatttt gtgttactca tagcgcgtaa tactgctaga gatctggcga 361 aagggggatg tgctgcaagg cgattaagtt gggtaacgcc agggttttcc cagtcacgac 421 gttgtaaaac gacggccagt gaattgtaat acgactcact atagggcgaa ttgggtactg 481 gccacaggag cttggcccat tgcatacgtt gtatccatat cataatatgt acatttatat 541 tggctcatgt ccaacattac cgccatgttg acattgatta ttgactagtt attaatagta 601 atcaattacg gggtcattag ttcatagccc, atatatggag ttccgcgtta cataacttac 661 ggtaaatggc ccgcctggct gaccgcccaa cgacccccgc ccattgacgt caataatgac 721 gtatgttccc atagtaacgc caatagggac tttccattga cgtcaatggg tggagtattt 781 acggtaaact gcccacttgg cagtacatca agtgtatcat atgccaagta cgccccctat 841 tgacgtcaat gacggtaaat ggcccgcctg gcattatgcx: cagtacatga ccttatggga 901 ctttcctact tggcagtaca tctacgtatt agtcatcgct attaccatgg tgatgcggtt 961 ttggcagtac atcaatgggc gtggatagcg gtttgactca cggggatttc caagtctcca 1021 ccccattgac gtcaatggga gtttgttttg gcaccaaaat caacgggact ttccaaaatg 1081 tcgtaacaac tcxxjccccat tgacgcaaat gggcggtagg cgtgtacggt gggaggtcta 1141 tataagcaga gctctcccta tcagtgatag agatctccct atcagtgata gagatcgtcg 1201 acgagctcgt ttagtgaacx: gtcagatcgc ctggagacgc catc:cacgct gttttgacct 1261 ccatagaaga caccgggacc gatccagcct gactctagcc tagctcctga gcctaggaga 1321 tctctcgagg tcgacggtat cgtgaccggt cttaagattt ccgccaccat gatgatggcx: 1381 agcaaggatg ccaccagctc tgtggatggt gcttctggtg ctggacagct ggtgcccgaa 1441 gtgaatgcct ctgatcccct ggccatggat cctgtggccg gatcttctac agccgtggct 1501 acagccggcc aagtgaaccc tatcgacccc, tggatcatca acaacttcgt gcaggcccct 1561 cagggcgagt tcacaatcag ccccaacaat acccctggcg acgtgctgtt cgacctgtct 1621 ctgggccctc acctgaatcc atttctgctg cacctgagcc, agatgtacaa cggctgggtc 1681 ggaaacatga gagtgcggat catgctggcc ggcaatgcct ttaccgccgg caagatcatc 1741 gtgtcttgca tcccacctgg cttcggcagc, cacaacctga caattgccca ggccacactg 1801 ttccctcacg tgatcgctga tgtgcggaca ctggatccta tcgaggtgcc cctggaagat 1861 gtccggaatg tgctgttcca caacaacgac cggaaccagc, agaccatgcg gctcgtgtgc1921 atgctgtaca cccc c gag aacaggcggc ggaaccggcg attcttttgt ggtggctggc 1981 ag gtag tga catgcccctc tccagac ta tac aacttcctgt tcctggtgcc tacct ccgtg 2041 gaacagaaaa cccggccttt cacactgccc aacctgcctc tgagcagcct gagcaattct 2101 agagcccctc tgcctatcag cagcatgggc atcagccccg ataaegtgea gagegtgeag 2161 ttccagaacg gcagatgtac cctggacggc agactcgtgg gcaccacacc tgtgtctctg 2221 tctcacgtgg ccaagatccg gggcacaagc aatggcaccg tgatcaacct gaccgagctg 2281 gatggcaccc catttcaccc ttttgagggc cctgctccta tcggctttcc tgatetegge 2341 ggctgcgact ggcacatcaa catgacacag ttcggccaca gcagccagac acagtacgac 2401 gtggacacaa cccctgacac cttcgtgcct cacctgggat ccatccaggc caatggcatc 2461 ggcagcggca atta a g c ggg egtgetgage tggatcagcc ctcc CL tetea ccctagcgga 2521 tctcaggtgg acctgtggaa gatccccaac tacggcagca gcatcaccga ggccacacat 2581 ctggccccat ctgtgtaccc acctggattt ggagaggtgc tggtgttctt2641 a tagcctgg c ctggcgccta caa tctgccta tagcctgctgc c caagag taa ca tcagccac 2701 ctggcctctg aac&ggcccc tacagttgga gaagccgcac tgctgcacta cgtggaccct 2761 gataccggca gaaacc ggg cg gttt ag gcttaccccg acggcttcct gacctgcgtt 2821 ccaaatggcg cctcttctgg acctcagcag ctgcccatca atggcgtgtt cgtgtttgtg 2881 tcc tagggtgt cccggttcta ccagctgaag cctgtggg cagccagca eget g gge 2941 agactgggcc tgagaagata gtgaaaateg ateggetage gtaccggcgg ccgccctatt 3001 ctatagt tc acctaaatgc t gagetege tgatcagcc ta cgac g gcc ttctagttgc 3061 cagccatctg ttgtttgccc ctcccccgtg ccttccttga ccctggaagg tgccactccc 3121 ac tagtaccttt c c t a at a a a a t g agga a a ta ta gcatcgc tt gte gagta gtagte ttet 3181 attctggggg gtggggtggg gcaggacagc, aagggggagg attgggaaga caatagcagg 3241 c a i-gc t gggg atgcggtggg ctctatggct taetgaggegg aaagaaccaa agettaegeg 3301 ttagttatta agcgatctgc atctcaatta gtcagcaacc, atagtcccgc ccctaactcc 3361 gcccatcccg cccctaactc cgcccagttc cgcccattct ccgccccatc gctgactaat 3421 tttttttatt tatgcagagg ccgaggccgc ctcggcctct gagctattcc agaagtagtg 3481 aggaggcttt tttggaggcc taggcttttg cgatccgcta gagatategg gccactgcag 3541 gaaacgatat gggctgaata cggatccgta ttcagcccat atcgtttctc tagaaataaa 3601 atatctttat tttcattaca tctgtgtgtt ggttttttgt gtgaategat agtactaaca 3661 tacgctctcc atctcgagcc taagettgte gactcgaaga tctgggcgtg gttaagggtg 3721 ggaaagaata tataaggtgg gggtcttatg tagttttgta tctgttttgc tgccgccgcc 3781 gccgcc tga gcaccaactc gt t taga gga agc ttgtga gctcatattt gac acgcgc 3841 atgcccccat gggccggggt gegteagaat gtgatgggct ccagcattga tggtcgcccc 3901 gtcct cccg c a a a c t c t a c taccttgacc taegagaeeg tagtctgga c gccgttggag 3961 actgcagcct ccgccgccgc ttcagccgct gcagccaccg cccgcgggat tgtgactgac 4021 ta ta tagctttcc tgagccc ct tgcaagcagta gc gcttccc gttcatccgc ccgcg tgac 4081 aagttgacgg ctcttttggc acaattggat tctttgaccc gggaaettaa tgtcgtttct 4141 cagcagctgt tgga tac tagcg cc gc ggtt tctgccctga aggcttcctc ccctcccaat 4201 gcggtttaaa a c. a t. a a a t ax ax aaaaccagac tctgtttgga tttggatcaa gcaagtgtct 4261 tgctgtcttt atttaggggt tttgcgcgcg cggtaggccc gggaccagcg gteteggteg 4321 ttgagggtcc tgtgtatttt ttccaggacg tggtaaaggt gactctggat gttcagatac 4381 a ugggcataa gcccgtctct ggggtggagg tagcaccact gcagagcttc atgetgeggg 4441 gtggtgttgt agatgatcca gtcgtagcag gagcgctggg cgtggtgcct aaaaatgtct 4501 ttcagtagca agctgattgc caggggcagg cccttggtgt aagtgtttac aaagcggtta 4561 agctgggatg ggtgcatacg tggggatatg agatgeatet tggactgtat ttttaggttg 4621 gctatgttcc cagccatatc cctccgggga ttcatgttgt gcagaaccac cagcacagtg 4681 tatccggtgc acttgggaaa tttgtcatgt agettagaag gaaatgegtg gaagaaettg 4741 gagacgccct tgtgacctcc aagattttcc atgeattegt ccataatgat ggcaatgggc 4801 ccacgggcgg cggcc tagggc g gat ttt ctggga tcac taaaegteata gtt tgttcc 4861 agga g a g a t cgtcataggc catttttaca aagcgcgggc ggagggtgcc agaetgeggt 4921 a taa tggttc c tccggccc aggggcgtaag tata ccctc c agatttgea t ta tacccacgct 4981 ttgagttcag atggggggat catgtctacc tgcggggcga L o.8. C) o.o.o. S C ggtttccggg 5041 gtaggggaga tcagc taggga agaaagcagg t tecta gage a getgegaett acc ca ccg 5101 gtgggcccgt aaatcacacc tattaccggc tgcaactggt agttaagaga getgeagetg 5161 ccgtcatccc tgagcagggg ggccac ta tacg agcatgt ccctgactcg ca tagttttcc 5221 ctgaccaaat ccgccagaag gcgctcgccg cccagcgata gcagttcttg caaggaagca 5281 aagtttttca a egg ta ta tag g accgtccgcc g aggca tagc tatttg gegt ttgaccaagc5341 agttccaggc ggtcccacag ctcggtcacc tgctctacgg catctcgatc cagcatatct 5401 cc tcgtttcg cgggttgggg cggctt tcgc tgtacggcag t tcggtgc tcgtcc gac 5461 gggccagggt catgtctttc. cacgggcgca gggtcctcgt cagcgtagtc tgggtcacgg 5521 tgaaggggtg cgctccgggc tgcgcgctgg ccagggtgcg cttgaggctg gtcctgctgg 5581 tgctgaagcg ctgccggtct tcgccctgcg cgtcggccag gtagcatttg accatggtgt 5641 catagtccag cccctccgcg gcgtggccct tggcgcgcag cttgcccttg gaggaggcgc 5701 cgcacgaggg gcagtgcaga cttttgaggg cgtagagctt gggcgcgaga aataccgatt 5761 ccggggagta ggcatccgcg ccgcaggccc cgcagacggt ctcgcattcc acgagccagg 5821 tgagctctgg ccgttcgggg tcaaaaacca ggtttccccc atgctttttg atgcgtttct 5881 tacctctggt ttccatgagc cggtgtccac gctcggtgac gaaaaggctg tccgtgtccc 5941 cgtatacaga cttgagaggc. ctgtcctcga gcggtgttcc gcggtcctcc tcgtatagaa 6001 actcggacca ctctgagaca aaggctcgcg tccaggccag cacgaaggag gctaagtggg 6061 aggggt gcg gtcgttgtcc actagggggt ccactcgctc cagggtgtga ag cac tgt 6121 cgccctcttc ggcatcaagg aaggtgattg gtttgtaggt gtaggccacg tgaccgggtg 6181 ttcct aagg ggggc t taa aagggggtgg g gcgcgttc gtcctcactc tcttccgcat 6241 cgctgtctgc gagggccagc tgttggggtg agtactccct ctgaaaagcg ggcatgactt 6301 c tgcgct g attgtcagtt tccaaaaacg gg ggattt gat ttcacc tggcccgcgg 6361 tgatgccttt gagggtggcc gcatccatct ggtcagaaaa gacaatcttt ttgttgtcaa 6421 gcttggtggc aaacgacccg tagagggcgt tggacagcaa cttggcg tg gagcgcaggg 6481 tttggttttt gtcgcgatcg gcgcgctcct tggccgcgat gtttagctgc acgtattcgc 6541 gcgcaacgca ccgccattcg ggaaagacgg tggtgcgctc gtcgggcacc aggtgc cgc 6601 gccaaccgcg gttgtgcagg gtgacaaggt caacgctggt ggctacctct ccgcgtaggc 6661 gctcgttggt ccagcagagg cggccgccct tgcgcgagca gaatggcggt agggggtcta 6721 gctgcgtctc gtccgggggg tctgcgtcca cggtaaagac cccgggcagc aggcgcgcgt 6781 cgaagtagtc tatcttgcat ccttgcaagt ctagcgcctg ctgccatgcg cgggcggcaa 6841 gcgcgcgctc gtatgggttg agtgggggac cccatggcat ggggtgggtg agcgcggagg 6901 cgtacatgcc gcaaatgtcg taaacgtaga ggggctctct gagtattcca ag tatgtag 6961 ggtagcatct tccaccgcgg atgctggcgc gcacgtaatc gtatagttcg tgcgagggag 7021 cgaggaggtc gggaccgagg ttgctacggg cgggctgctc tgctcggaag actatctgcc 7081 tgaagatggc atgtgagttg gatgatatgg ttggacgctg gaagacgttg aagctggcgt 7141 ctgtgagacc taccgcgtca cgcacgaagg aggcgtagga gtcgcgcagc ttgttgacca 7201 gc tcggcggt gacctgcacg tctagggcgc agt gtcc g ggtttccttg a tg tgtcat 7261 acttatcctg tccctttttt ttccacagct cgcggttgag gacaaactct tcgcggtctt 7321 tccagt ctc ttgga tcgga aacccgtcgg cctccgaacg gt gagcct gcatgtaga 7381 actggttgac ggcctggtag gcgcagcatc ccttttctac gggtagcgcg tatgcctgcg 7441 cggccttccg gagcgag t tgggtgagcg c aggtgtc cctgaccatg ac tttgaggt 7501 actggtattt gaagtcagtg tcgtcgcatc cgccctgctc CC 8. o. C) C o. S S aagtccgtgc 7561 gctttttgga acgcgga ttt ggc gggcga aggtgacatc gttgaagagt atctttcccg 7621 cgcgaggcat aaagttgcgt gtgatgcgga agggtcccgg cacctcggaa cggttgttaa 7681 ttacctgggc ggcgagcacg atctcgtcaa agccgttgat gttgtggccc acaatgtaaa 7741 gttccaagaa gcgcgggatg cccttgatgg aaggcaattt tttaagttcc tcgtaggtga 7801 gctcttcagg ggagctgagc ccgtgctctg aaagggccca gtctgcaaga cga gggt t g 7861 aagcgacgaa tgagctccac aggtcacggg ccattagcat ttgcaggtgg tcgcgaaagg 7921 tcctaaactg gcgacctatg gccatttttt ctggggtgat gcagtagaag gtaagcgggt 7981 cttgttccca gcggtcccat ccaaggttcg cggctaggtc tcgcgcggca gtcactagag 8041 gctcatctcc gccgaacttc atgaccagca tgaagggcac gagctgcttc CC3< H< HC C CCC 8101 ccatccaagt ataggtctct acatcgtagg tgacaaagag acgctcggtg cgaggatgcg 8161 agccgatcgg gaagaactgg atctcccgcc accaattgga ggagtggcta ttgatgtggt 822 gaaagta aa gtccc tgcga cgggccg c actcgtgctg gcttttgtaa aa c t cgc 8281 agtactggca gcggtgcacg ggctgtacat cctgcacgag gttgacctga cgaccgcgca 8341 c aggaagca gagtggga t ttgagcccc t: cgcctggcgg gtttggctgg tggtcttcta 8401 cttcggctgc ttgtccttga ccgtctggct gctcgagggg agttacggtg gatcggacca 8461 ccacgcc cg cgagcccaaa gtccag tgt ccgcgcgcgg cggtcgg gc ttg t caa 8521 catcgcgcag atgggagctg tccatggtct ggagctcccg cggcgtcagg tcaggcggga 8581 gc tcctgc g gttt cctcg catagacggg tc gggcgcg ggctagatcc aggtg t cc 8641 taatttccag gggctggttg gtggcggcgt cgatggcttg caagaggccg catccccgcg 8701 gcgcgactac ggtaccgcgc ggcgggcggt g gccgcggg ggtgtccttg g t t cat8761 ctaaaagcgg tgacgcgggc gagcccccgg aggtaggggg ggctccggac ccgccgggag 882 agggggcagg ggcacgtcgg cgccgcgcgc gggcaggagc g gctgcg egegt gg 8881 gctggcgaac gcgacgacgc ggcggttgat ctcctgaatc tggcgcctct gcgtgaagac 8941 gacgggcccg gtgagcttga acctgaaaga gagttcgaca gaatcaattt cggtgtcgtt 9001 gacggcggcc tggcgcaaaa tctcctgcac gtctcctgag ttgtcttgat aggcgatctc 9061 ggccatgaac tgctcgatct cttcctcctg gagateteeg cgtccggctc gctccacggt 9121 ggcggcgagg tcgttggaaa tgcgggccat gagetgegag aaggcgttga ggcctccctc 9181 gttccagacg cggctgtaga ccacgccccc ttcggcatcg cgggcgcgca tgaccacctg 9241 cgcgagattg agctccacgt gccgggcgaa gaeggegtag tttcgcaggc getgaaagag 9301 gtagttgagg gtggtggcgg tgtgttctgc cacgaagaag tacataaccc agcgtcgcaa 9361 cgtggattcg ttgatatccc ccaaggcctc, aaggcgctcc atggcctcgt agaagtccac 9421 ggcgaagttg aaaaactggg agttgcgcgc cgacacggtt aactcctcct CCa aa CCf 9481 ga tgagctcg gcgacagtgt cgcgcacc tc gcgctcaaa gc acagggg cc tettette 9541 ttcttcaatc tcctcttcca taagggcctc cccttcttct tcttctggcg gcggtggggg 9601 aggggggaca cggcggcg c gacggc c c cggga ggegg tcg caaagc gc cga ca 9661 c tccccgcgg cgacggcgca tggtctcggt gaeggegegg ccgttctcgc gggggcgcag 9721 gg g cg ccgcccgtca g cccggt t: atgggttggc ggggggctgc ca tgcggcag 9781 ggatacggcg ctaacgatgc atctcaacaa ttgttgtgta ggtactccgc egeegaggga 9841 cctgagcgag tccgca tcga ccggatcgga aaacc teteg agaaaggegt ctaaccagtc 9901 a c a g u cgc ggtaggctga gcaccgtggc gggcggcagc gggcggcggt cggggttgtt 9961 tc tggcggag gtgctgctga tga tgtaa t: t aaagtaggc g c gagac ggcgg tggt 10021 cgacagaagc accatgtcct tgggtccggc etgetgaatg egeaggeggt cggccatgcc 10081 ccaggcttcg ttttgacatc ggcgcaggtc tttgtagtag tettgeatga gcctttctac 10141 cggcacttct tcttctcctt cctcttgtcc tgeatetett gcatctatcg ctgcggcggc 10201 ggcggagttt ggccgtaggt ggcgccctct tcctcccatg cgtgtgaccc cgaagcccct 10261 catcggctga agcagggcta ggtcggcgac aacgcgctcg getaatatgg cctgctgcac 10321 ctgcgtgagg gtagactgga agtcatccat gtccacaaag cggtggtatg cgcccgtgtt 10381 gatggtgtaa gtgcagttgg ccataacgga ccagttaacg gtctggtgac ccggctgcga 10441 gagctcggtg tacc i-gagac gcgagtaagc cctcgagtca a a t a cqt CL gt cgttgcaagt 10501 ccgcaccagg tactggtatc gtgeggegge ggctggcggt agaggggcca 10561 gcgtagggtg gccggggctc cgggggcgag atcttccaac ataaggegat gatatccgta 10621 g tgt cc g gacatccagg ga tgccggc ggcggtggt gag egegeg gaaagtegeg 10681 gacgcggttc cagatgttgc gcagcggcaa aaagtgctcc atggtcggga cgctctggcc 10741 ggtc gcgc gcgcaa tcgt tgacgctcta gegtgeaaaa ggagagcctg taagegggea 10801 ctcttccgtg gtctggtgga taaattcgca agggtatcat ggcggacgac cggggttcga 10861 gccccgt c cggccgtccg ccg tga tcca tgcggttacc gcccgcg gt cgaacccagg 10921 tgtgcgacgt cagacaacgg gggagtgctc cttttggctt ccttccaggc geggeggetg 10981 ctgcgctagc ttttttggcc actggccgcg egeagegtaa geggttagge ggaaa ega 11041 aagcattaag tggctcgctc cctgtagccg gagggttatt ttccaagggt tgagtegegg 11101 gacccccggt tcgagtctcg gaccggccgg aetgeggega acgggggttt gcctccccgt 11161 catgcaagac cccgcttgca aattcctccg gaaacaggga cgagcccctt ttttgctttt 11221 cccagat ca tccggtgctg cggcagatgc gcccccctcc tcagcagcgg Caa a C Cf 11281 agcagcggca gacatgcagg gcaccctccc ctcctcctac egegteagga ggggcgacat 11341 ccgcggttga cgcggcagca gatggtgatt acgaaccccc gcggcgccgg gcccggcact 11401 acctggactt ggaggagggc gagggcctgg egeggetagg agcgccctct cctgagcggc 11461 acccaa qt gcagctgaag cgtgatacgc gtgaggcgta cgtgccgcgg cagaacctgt 11521 ttcgcgaccg cgagggagag gagcccgagg agatgeggga tegaaagtte cacgcagggc 11581 gcgagctgcg gcatggcctg aatcgcgagc ggttgctgcg cgaggaggac tttgagcccg 11641 acgcgcgaac cggga t: t gt cccgcgcgcg cacacgtggc ggccgccgac e gg aaeeg 11701 catacgagca gacggtgaac caggagatta actttcaaaa aagctttaac aaccacgtgc 11761 g tacgcttgt ggcgcgcgag gaggtggc ta taggaetgat gca c g gg gactttgtaa 11821 gcgcgctgga gcaaaaccca aatagcaagc cgctcatggc gcagctgttc ettatagtge 11881 agcacagcag ggacaacg g gcattcaggg a gegetge t: aaacatagta gagcccgagg 11941 gccgctggct gctcgatttg ataaacatcc tgcagagcat agtggtgcag gagcgcagct 12001 tgagcctggc tgac ag t gccgcca te actattccat ge agee tg ggcaagt tt 12061 acgcccgcaa gatataccat accccttacg ttcccataga caaggaggta aagategagg 12121 gg c aca gcgca tggcg etgaaggtge acc ttgag cgacgacctg ggc a c12181 gcaacgagcg catccacaag geegtgageg tgagccggcg gcgcgagctc agcgaccgcg 12241 age g gea cagcctgcaa agggccc gg c ggc cggg cagcggcga agagaggeeg 12301 agtcctactt tgacgcgggc gctgacctgc gctgggcccc aagccgacgc gccctggagg 12361 Ca C L g CfC cggacctggg ctggcggtgg cacccgcgcg cgctggcaac gtcggcggcg 12421 tggaggaata tgacgaggac gatgagtacg agccagagga cggcgagtac taageggtga 12481 tgtttctgat cagatgatgc aagacgcaac ggacccggcg gtgcgggcgg egetgeagag 12541 ccagccgtcc ggccttaact ccacggacga ctggcgccag gtcatggacc gcatcatgtc 12601 getgaetgeg cgcaatcctg acgcgttccg gcagcagccg caggccaacc ggctctccgc 12661 aattctggaa gcggtggtcc cggcgcgcgc aaaccccacg cacgagaagg tgctggcgat 12721 cgtaaacgcg ctggccgaaa acagggccat ccggcccgac gaggccggcc tggtetaega 12781 cgcgctgctt cagcgcgtgg ctcgttacaa cagcggcaac gtgcagacca acctggaccg 12841 gctggtgggg gatgtgcgcg aggeegtgge gcagcgtgag cgcgcgcagc agca Co.8.12901 cc gggc cc tgg gcac taaaegee cctg gt c cagcccgcca acg gccgcg 12961 gggacaggag gactacacca actttgtgag cgcactgcgg ctaatggtga ctgagacacc 13021 gcaaagtgag g g acc g ctgggccaga ctatt tt c c g ccagt gacaaggcct 13081 gcagaccgta aacctgagcc aggctttcaa aaacttgcag gggctgtggg gggtgcgggc 13141 cccacaggc gaccgcgcga ccg g c ag c tgctg cg cccaactcgc gcc g gct 13201 getgetaata gcgcccttca cggacagtgg cagcgtgtcc cgggacacat acctaggtca 13261 cttgctgaca c g accgcg aggcc gg teaggegea t g gg cg gc atactttcca 13321 ggagattaca agtgtcagcc gcgcgctggg gcaggaggac acgggcagcc g g a g g c a a c 13381 cc aa c ac ctgc g cca accggcggca gaagatcccc cgttgcaca g a cag 13441 egaggaggag cgcattttgc getaegtgea gcagagcgtg agccttaacc tgatgegega 13501 cggggtaacg cccagcgtgg cgctggacat gaccgcgcgc aacatggaac cgggcatgta 13561 tgcctcaaac cggccgttta tcaaccgcct aatggactac ttgcatcgcg cggccgccgt 13621 gaaccccgag tatttcacca atgccatctt gaacccgcac tggctaccgc cccctggttt 13681 ctacaccggg ggattegagg tgcccgaggg taaegatgga ttcctctggg acgacataga 13741 cgacagcgtg ttttccccgc aaccgcagac cctgctagag ttgcaacagc gcgagcaggc 13801 agaggeggeg etgegaaagg aaagetteeg caggccaagc agettgteeg atetaggege 13861 tgcggccccg eggteagatg ctagtagccc atttccaagc ttgatagggt ctcttaccag 13921 cactcgcacc acccgcccgc gcctgctggg egaggaggag tacctaaaca actcgctgct 13981 gcagccgcag egegaaaaaa acctgcctcc ggcatttccc aacaacggga tagagagcct 14041 ag gg c g tg g g t ggaagacg a cgcgc gg g cacagggacg gccaggccc 14101 gcgcccgccc acccgtcgtc aaaggcacga ccgtcagcgg ggtctggtgt gggaggaega 14161 tgactcggca gacgacagca gegtee gga tttgggaggg agtggcaacc cg ttgcgca 14221 ccttcgcccc aggctgggga gaatgtttta a a O. O. O. d d d d 3 gcatgatgca aaataaa 8.8.8.14281 c cacca gg cc tggc cc gageg gg tcttgt ccccttagt a tgcggcgcg 14341 cggcgatgta tgaggaaggt cctcctccct cctacgagag tgtggtgagc gcggcgccag 14401 tggeggegge gctggg c cccttcgatg ctcccc gga cccgccgttt g gcctccgc 14461 ggtacctgcg gcctaccggg gggagaaaca gcatccgtta ctctgagttg gcacccctat 14521 tcgacaccac ccgtgtgtac ctggtggaca acaagtcaac ggatgtggca tccctgaact 14581 accagaacga ccacagcaac tttctgacca eggteattea aaacaatgac tacagcccgg 14641 gggaggcaag cacacagacc atcaatcttg acgaccggtc gcactggggc ggcgacctga 14701 aaaccatcct gcataccaac atgccaaatg tgaacgagtt catgtttacc aataagttta 14 ’ 61 aggcgcgggt gatggtgtcg cgcttgccta ctaaggacaa tcaggtggag ctgaaatacg 14821 agtgggtgga gttcacgctg cccgagggca actactccga gaccatgacc atagacctta 14881 tgaacaacgc gategtggag cactacttga aagtgggcag acagaacggg gttctgg ddd 14941 gcgacatcgg ggtaaagttt gacacccgca acttcagact ggggtttgac cccgtcactg 15001 gtcttgtcat gcctggggta tatacaaacg aagccttcca tccagacatc attttgctgc 15061 c gg tgcgg ggtggac c acccac gcc gcctgagca c gttgggc atccgcaagc 15121 ggcaaccctt ccaggagggc tttaggatca cctacgatga tctggagggt ggtaacattc 15181 ccgcac gtt gg tg ggac gcc accagg egagettg agatgacacc gaacagggcg 15241 ggggtggcgc aggcggcagc aacagcagtg gcagcggcgc ggaagagaac tccaacgcgg 15301 c gccgcggc aa geageeg gtggaggaca tgaaega ea gccattcgc ggcgacacct 15361 ttgccacacg ggetgaggag aagcgcgctg aggeegaage ageggeegaa gctgccgccc 15421 ccgctgcgca acccgaggtc gagaagee c agaagaaacc ggtgatcaaa cccc g cag 15481 aggacagcaa gaaacgcagt tacaacctaa taagcaatga cagcaccttc acccagtacc 15541 gcagctggta cc gca c aactacggcg accctcagac cgg tccgc c tggaccc15601 tgctttgcac tcctgacgta acctgcggct cggagcaggt ctactggtcg u u^cca^sc o.15661 tga tgca ga ccccgtgacc ttxxxjc txx:a cgcgccag t cagcaacttt ccggtggtgg 15721 gcgccgagct gttgcccgtg cactccaaga gcttctacaa cgaccaggcc gtctactccc 15781 aactcatccg ccagtttacc tctctgaccc acgtgttcaa tcgctttccc cj3cj<a<acc>ac[>a 15841 ttttggcgcg cccgccagcc cccaccatca ccaccgtcag tgaaaacgtt cctgctctca 15901 cagatcacgg gacgctaccg ctgcgcaaca gcatcggagg agtccagcga gtgaccatta 15961 ctgacgccag acgccgcacc tgcccctacg tttacaaggc cctgggcata gtctcgccgc 16021 gcgtcctatc gagccgcact ttttgagcaa gcatgtccat ccttatatcg cccagcaata 16081 acacaggctg gggcctgcgc ttcccaagca agatgtttgg cggggccaag aagcgctccg 16141 accaacaccc agtgcgcgtg cgcgggcact accgcgcgcc ctggggcgcg cacaaacgcg 16201 gccgcactgg gcgcaccacc gtcgatgacg ccatcgacgc ggtggtggag gaggcgcgca 16261 actacacgcc cacgccgcca ccagtgtcca cagtggacgc ggccattcag accgtggtgc 16321 gcgg gcccg gcgctat ct aaaatgaaga g cggcgg g gcgcgtagca cgtcgccacc 16381 gccgccgacc cggcactgcc gcccaacgcg cggcggcggc cctgcttaac cgcgcacgtc 16441 gcacc gccg acgggcggcc tgcgggcxrg ctcgaaggc t: ggccgcgggt att tcactg 16501 tgccccccag gtccaggcga cgagcggccg ccgcagcagc cgcggccatt agtgctatga 16561 c tcagggtcg caggggcaac gtgtat t jgg tgcgcgactc ggttagcggc c tgcgcgtgc 16621 ccgtgcgcac ccgccccccg cgcaactaga ttgcaagaaa aaactactta gactcgtact 16681 gttgtat ta ccagcggcg gcggcgcgc acgaagcta t: gtcc agcgc aaaatcaaag 16741 aagagatgct ccaggtcatc gcgccggaga tctatggccc cccgaagaag gaagagcagg 16801 < 6 C.33 (J C C ccgaaagcta aagcgggtx:a a agaaa gaaagatgat g Og tgaac 16861 ttgacgacga ggtggaactg ctgcacgcta ccgcgcccag gcgacgggta cagtggaaag 16921 gtcgacgcgt aaaacgtgtt ttgcgacccg gcaccaccgt agtctttacg cccggtgagc 16981 gctccacccg cacctacaag cgcgtgtatg atgaggtgta cggcgacgag gacctgcttg 17041 agcaggccaa cgagcgcctc ggggagtttg cctacggaaa gcggcataag gacatgctgg 17101 cgttgccgct ggacgagggc -- l dl *2* dl *22 ctagcctaaa gcccgtaaca ctgcagcagg 17161 tgctgcccgc gcttgcaccg tccgaagaaa agcgcggcct aaagcgcgag ggt gac t 17221 tggcacccac cgtgcagctg atggtaccca agcgccagcg actggaagat gtcttggaaa 17281 aaatgaccgt ggaacctggg ctggagcccg aggtccgcgt gcggccaatc aagcaggtgg 17341 cgccgggact gggcgtgcag accgtggacg ttcagatacc cactaccagt agcaccagta 17401 ttgccaccgc cacagagggc atggagacac aaacgtcccc ggttgcctca gcggtggcgg 17461 a tgccgcggt gcaggcg tc gctgcggccg cgtcc ag c ctx:tacgga gtgcaa cgg 17521 acccgtggat gtttcgcgtt tcagcccccc ggcgcccgcg ccgttcgagg aagtacggcg 17581 ccgccagcgc gctac tgccc gaatatgcxx: tacatcct c c ttgcgcct acccccggct 17641 a c g g g c t a cacctaccgc cccagaagac gagcaactac ccgacgccga accaccactg 17701 gaacccgccg ccgccgtcgc cgtxxjcx: gc ccgtgctggc cxx:gatttxx: gtgcgc ggg 17761 tggctcgcga aggaggcagg accctggtgc tgccaacagc gcgctaccac cccagcatcg 17821 tttaaaagcc gg c t: t: t:gtg gttcttgcag atatggccc t: c cctgccgc ctccgtttcx: 17881 cggtgccggg attccgagga agaatgcacc gtaggagggg catggccggc cacggcctga 17941 cgggcggcat gcgtcgtgcg caccaccggc ggcggcgcgc gtcgcaccgt cgcatgcgcg 18001 gcggtatcct gcccctcctt attccactga tcgccgcggc gattggcgcc gtgcccggaa 18061 ttgcatccgt ggccttgcag gcgcagagac actgattaaa aacaagttgc ugtggaaaa 18121 a tcaaaat aa aaagtctgga ctctcacgct cgcttggtcc, tgtaactatt ttgtagaatg 18181 gaagacatca actttgcgtc tctggccccg cgacacggct cgcgcccgtt catgggaaac 18241 tggcaagata tcggcaccag caatatgagc, ggtggcgcct tcagctgggg ctcgctgtgg 18301 agcggcatta aaaatttcgg ttccaccgtt aagaactatg gcagcaaggc ctggaacagc 18361 agcacaggcc agatgctgag ggataagttg aaagagcaaa atttccaaca aaaggtggta 18421 gatggcctgg cctctggcat tagcggggtg gtggacctgg ccaaccaggc agtgcaaaat 18481 aagattaaca gtaagc tatga tccccgcxxrt cccgtagagg agcctccacc ggcx:gtggag 18541 acagtgtctc cagaggggcg tggcgaaaag cgtccgcgcc ccgacaggga agaaactctg 18601 g tgacgc a t g cg cc txxx:tx jt: c g gg ggc c taaagcaagg cc tgcccacc 18661 acccgtccca tcgcgcccat ggctaccgga gtgctgggcc agcacacacc cgtaacgctg 18721 gacct cctc cccccgccga cacccagcag aaacx:tgtgc txjcc ggccc g cx: cx:gtt 18781 gttgtaaccc gtcctagccg cgcgtccctg cgccgcgccg ccagcggtcc gcgatcgttg 18841 cggcccgt g ccagtggcaa ctggca agc acactgaaca gcatxxjtggg tx: tgggggtg 18901 caatccctga agcgccgacg atgcttctga tagctaacgt gtcgtatgtg tgtcatgtat 18961 gcgtccatgt cgccgcc ga gg gctgctg a cxxjcxxjcg cgcccgcttt cxraagatggc19021 taccccttcg atgatgeege agtggtctta catgcacatc tcgggccagg acgcctcgga 19081 t acct g ge cccgggctgg tgcagt t: tgc ccgcgccacc gagacgtact tcagcctgaa 19141 taacaagttt agaaacccca cggtggcgcc tacgcacgac gtgaccacag accggtccca 19201 gcgtttgacg etgeggttea tccctgtgga ccgtgaggat actgcgtact cgtacaaggc 19261 gcggttcacc ctagctgtgg gtgataaccg tgtgctggac atggcttcca cgtactttga 19321 catccgcggc gtgctggaca ggggccctac ttttaagccc tactctggca ctgcctacaa 19381 cgccctggct cccaagggtg C C C C cl cl d L C C ttgcgaatgg gatgaagctg ctactgctct 19441 tgaaataaac ctagaagaag aggacgatga caacgaagac gaagtagacg agcaagctga 19501 gcagcaaaaa actcacgtat ttgggcaggc geettattet ggtataaata ttacaaagga 19561 gggtattcaa ataggtgteg aaggtcaaac acctaaatat gccgataaaa catttcaacc 19621 tgaacctcaa ataggagaat ctcagtggta cgaaacagaa attaatcatg cagctgggag 19681 ag Lcctaa dd aagactaccc caatgaaacc atgttacggt tcatatgcaa ddCCCdCddd 19741 tgaaa tgga gggcaaggca ttcttg taaa gcaacaaaat ggaaagcta aaagtcaagt 19801 ggaaatgcaa tttttctcaa ctactgaggc agccgcaggc aatggtgata acttgactcc 19861 taaagtggta ttgtacagtg aagatgtaga tatagaaacc ccagacactc at tttctta 19921 catgcccact attaaggaag gtaactcacg agaactaatg ggccaacaat ctatgcccaa 19981 caggcctaat t c ttgctt ttagggacaa tttt ttggt cta tgtatt acaacagcac 20041 gggtaatatg ggtgttctgg cgggccaagc atcgcagttg aatgctgttg tagatttgca 20101 gac ga ac acagagc tt c t cc gct tttgcttga t tcc ttggtg atagaaccag 20161 gtacttttct atgtggaatc aggctgttga cagctatgat ccagatgtta gaattattga 20221 aaa tcatgga ae gaag g aacttccaaa tt ctgcttt ccactggga gtgtg tt 20281 tacagagact cttaccaagg taaaacctaa aacaggtcag gaaaatggat gggaaaaaga 20341 t gc eacagaa ttttcagata aaaatgaaat aagagttgga aataattttg ccatggaaat 20401 caatctaaat gccaacctgt ggagaaattt cctgtactcc aacatagcgc tgtatttgcc 20461 cgacaagcta aagtacagtc cttccaacgt aaaaatttct gataacccaa acacctacga 20521 ctacatgaac aagcgagtgg tggctcccgg gctagtggac tgctacatta accttggagc 20581 acgctggtcc cttgactata tggacaacgt caacccattt aaccaccacc gcaatgctgg 20641 cctgcgctac cgctcaatgt tgctgggcaa tggtegetat gtgcccttcc acatccaggt 20701 gcctcagaag ttctttgcca ttaaaaacct ccttctcctg ccgggctcat acacctacga 20761 gtggaacttc aggaaggatg ttaacatggt tetgeagage tccctaggaa atgacctaag 20821 ggttgacgga gccagcatta agtttgatag catttgcctt tacgccacct tcttccccat 20881 ggcccacaac accgcctcca cgcttgaggc c tgctt ga aacgacacca acgacc g c 20941 ctttaacgac tatctctccg ccgccaacat gctctaccct atacccgcca acgctaccaa 21001 cgtgccc ta tcca tcccc cccgcaactg ggcggctttc cgcggctggg cc cacgcg 21061 ccttaagact aaggaaaccc catcactggg ctcgggctac gacccttatt acacctactc 21121 tggc tct ta ccctacctag atggaacc t: t: tt cctca c cacaccttta aga gg ggc 21181 cattaccttt gactcttctg tcagctggcc tggcaatgac cgcctgctta cccccaacga 21241 gtttgaa tt aagege tcag ttgacgggga gggttacaac gttgcccagt gtaaca gac 21301 caaagactgg ttcctggtac aaatgctagc taactataac attggctacc agggcttcta 21361 tatcccagag agctacaagg accgcatgta ctccttcttt agaaacttcc agcccatgag 21421 ccgtcaggtg gtggatgata ctaaatacaa ggactaccaa caggtgggca tcctacacca 21481 dCdCddCddC tctggatttg ttggctacct tgcccccacc atgcgcgaag gacaggccta 21541 ccctgctaac ttcccctatc cgcttatagg caagaccgca gttgacagca ttacccagaa 21601 aaagtttctt tgegategea ccctttggcg catcccattc tccagtaact ttatgtccat 21661 gggcgcactc acagacctgg g C C cl cl cl d C C L tctctacgcc aactccgccc acgcgctaga 21721 catgactttt gaggtggatc ccatggacga gcccaccctt ctttatgttt eg ettgaagt 21781 ctttgacgtg gtccgtgtgc accagccgca ccgcggcgtc atcgaaaccg tgtacctgcg 21841 cacgcccttc tcggccggca acgccacaac ataaagaagc aagcaacatc aacaacagct 21901 gccgccatgg gctccagtga gc gg ctg aaagccattg tcaaagatct tggttg ggg 21961 ccatattttt tgggcaccta tgacaagcgc tttccaggct ttgtttctcc acacaagctc 22021 gcc tgcgcca g ca c ggccgg tcgc g g ctgggg gcgtacactg ga tggccttt 22081 gcctggaacc cgcactcaaa aacatgctac ctctttgagc cctttggctt ttctgaccag 22141 cgactca gc aggt t tacca gtttg gt c gagtcactcc tgcgccgt g cgccattgct 22201 tcttcccccg accgctgtat aacgctggaa aagtccaccc aaagcgtaca g g g g c c c 8.8. c 22261 tcggccgcct gtggac tt ctgctgca t:g tttctccacg cctttgccaa c tiggcccc88 22321 actcccatgg atcacaaccc caccatgaac ettattaeeg gggtacccaa ctccatgctc 22381 cagtcccc aggtacagcc caccctgcgt cgcaaccagg aacagctcta cagcttcctg22441 gagcgccact cgccctactt ccgcagccac agtgcgcaga ttaggagege cacttctttt 2250 gtcacttga aaaacatgta aaaatiaaege act gagac ctttcaataa aggcaa tgc 22561 ttttatttgt acactctcgg gtgattattt acccccaccc ttgccgtctg cgccgtttaa 22621 Helal LCaaaQQ ggttctgccg cgcatcgcta tgcgccactg gcagggacac g c egcgatac 22681 tggtgtttag tgctccactt aaactcaggc acaaccatcc, gcggcagctc ggtgaagttt 22741 tcactccaca ggctgcgcac catcaccaac gcgtttagca ggtcgggcgc egatatettg 22801 aagtcgcagt tggggcctcc gccctgcgcg cgcgagttgc gatacacagg gttgcagcac 22861 tggaacacta tcagcgccgg gtggtgcacg ctggccagca cgctcttgtc ggagatcaga 22921 tccgcgtcca ggtcctccgc gttgctcagg gegaaeggag tcaactttgg tagetgeett 22981 cccaaaaagg gcgcgtgccc aggetttgag ttgcactcgc accgtagtgg catcaaaagg 23041 tgaccgtgcc cggtctgggc gttaggatac agcgcctgca taaaageett gatetgetta 23101 aaagccacct gagcctttgc gccttcagag aagaacatgc egeaagaett CC gaaaaC 23161 tga t: tggeeg gac ggccgc gtcgtgcacg cagcaccttg cgtcggtgtt ggag tctgc 23221 accacatttc ggccccaccg gttcttcacg atcttggcct tgctagactg ctccttcagc 23281 gcgcgctgcc cgtt t: teget cgtcac tcc atttcaatca cgtgctcctt atttatcata 23341 atgcttccgt gtagacactt aagctcgcct tcgatctcag egeageggtg c a g e e H c a a c 23401 gcgcagcccg tgggctcgtg atget gtag gtcacctctg caaacgactg caggt cgcc 23461 tgeaggaate gccccatcat cgtcacaaag gtcttgttgc tggtgaaggt cagctgcaac 23521 ccgcggtgct cctcgt: t:cag ccaggtcttg c tacggccg ccagagcttc cacttggtca 23581 ggcagtagtt tgaagttcgc etttagateg ttatccacgt ggtacttgtc catcagcgcg 23641 cgcgc gcct ccatgccctt ctcccacgca gacacgatcg gcacactcag cgggttcatc 23701 accgtaattt cactttccgc ttcgctgggc tcttcctctt cctcttgcgt ccgcatacca 23761 cgcgccactg ggtegtette attcagccgc cgcactgtgc gcttacctcc tttgccatgc 23821 ttgattagca ccggtgggtt gctgaaaccc accatttgta gcgccacatc ttctctttct 23881 tcctcgctgt ccacgattac ctctggtgat ggcgggcgct cgggcttggg agaagggege 23941 ttctttttct tcttgggcgc aatggccaaa tccgccgccg aggtegatgg ccgcgggctg 24001 ggtgtgcgcg gcaccagcgc gtcttgtgat gagtcttcct cgtcctcgga ctcgatacgc 24061 cgcctcatcc gcttttttgg gggcgcccgg ggaggcggcg gcgacgggga cggggacgac 24121 acgtcctcca tggttggggg acgtcgcgcc gcaccgcgtc cgcgctcggg ggtggtttcg 24181 cgctgctcct cttcccgact ggccatttcc, ttctcctata ggcagaaaaa gatcatggag 24241 teagtegaga agaaggacag cctaaccgcc ccctctgagt tcgccaccac cgcctccacc 24301 g t: gee gee a acgcgcctac caccttcccc gtcg ggc c ccccgcttga ggagg gg 24361 gtgattateg agcaggaccc aggttttgta agcgaagacg aegaggaeeg ctcagtacca 24421 acagaggata a a a a gca a a ccaggacaac gcagaggcaa acg gga ca agtcgggcgg 24481 ggggacgaaa ggcatggcga ctacctagat gtgggagacg acgtgctgtt gaagcatctg 24541 cagcgcc gt gcgccattat ctgcgacgcg tt gc gage gcagcgatgt gcccctcgcc 24601 atageggatg tcagccttgc ctacgaacgc cacctattct caccgcgcgt accccccaaa 24661 cgccaagaaa acggcac tg cgagcccaac ccgcgcctca acttctaccc cgt tttgcc 24721 gtgccagagg tgcttgccac ctatcacatc tttttccaaa aetgeaagat acccctatcc 24781 tgccgtgcca accgcagccg agcggacaag cagctggcct tgcggcaggg egetgteata 24841 cctgatatcg cctcgctcaa cgaagtgcca aaaatctttg agggtcttgg aegegaegag 24901 aagegegegg caaacgctct gcaacaggaa aacagcgaaa atgaaagtea c cetggagtg 24961 ttggtggaac tcgagggtga caacgcgcgc ctagccgtac, taaaacgcag catcgaggtc 25021 acccactttg cctacccggc acttaaccta ccccccaagg tcatgagcac agteatgagt 25081 gagetgateg tgcgccgtgc gcagcccctg gagagggatg caaatttgca agaacaaaca 25141 aCjCja CC tacccgcagt tggegaegag cagctagcgc getggettea aac c cQHQ 25201 cctgccgact tggaggagcg acgcaaacta atgatggeeg cagtgctcgt taccgtggag 25261 ettgagtgea tgcagcggtt ctttgctgac ccggagatgc agcgcaagct agaggaaaca 25321 ttgcactaca cctt tcgaca gggct cgt cgccaggcc t: gcaagatctc caacgtggag 25381 ctctgcaacc tggtctccta ccttggaatt ttgcacgaaa accgccttgg gcaaaacgtg 25441 c t: tcattcca cgctcaaggg cgaggcgcgc cgcg ct cg tccgcgactg cgtttactta 25501 tttetatget acacctggca gacggccatg ggcgtttggc ageagtgett ggaggagtgc 25561 cctca gg agetgeag aetget aag caaaacttga aggacct tg gacggccttc 25621 aaegageget ccgtggccgc gcacctggcg gacatcattt tccccgaacg cctgctt a a a 25681 accc tgcaac agggtetgee agacttcacc agte age tgttgcagaa c t: ttaggaac 25741 tttatcctag agcgctcagg aatcttgccc gccacctgct gtgcacttcc tagegaettt 25801 gtgcccatta agtaccgcga tgccctccg ccgctttggg gcc ctgct ccttctgcag25861 ctagccaact accttgccta ccactctgac ataatggaag aegtgagegg tgaeggteta 2592 c tggagtgtc actgtcgctg caaccta gc accccgcacc gctccctggt gea tteg 25981 cagctgctta aegaaagtea aattatcggt acctttgagc tgcagggtcc ctcgcctgac 26041 gaaaagtccg cggctccggg gttgaaactc actccggggc tgtggacgtc ggcttacctt 26101 cgcaaatttg tacctgagga ctaccacgcc cacgagatta ggttctacga agaccaatcc 26161 cgcccgccta atgeggaget taccgcctgc gtcattaccc agggccacat tcttggccaa 26221 ttgcaagcca tcaacaaagc. ccgccaagag tttctgctac gaaagggacg gggggtttac 26281 ttggaccccc agteeggega ggagctcaac ccaatccccc cgccgccgca gccctatcag 26341 cagcagccgc gggcccttgc ttcccaggat ggc.ac.ccaaa aagaagctgc agctgccgcc 26401 gccacccacg aatactggga cagtcaggca gaggaggttt tggaegagga 26461 ggaggaggac atgatggaag actgggagag cctagacgag gaagetteeg aggtegaaga 26521 ggtgtcagac gaaacaccgt caccctcggt cgcattcccc tcgccggcgc cccagaaatc 26581 ggcaaccggt tcc gc t g ctacaacc c cgctcctcag gcgccgccgg cactgcccgt 26641 tcgccgaccc aaccgtagat gggacaccac tggaaccagg geeggtaagt ccaagcagcc 26701 gccgccgtta gcccaagagc aacaacagcg ccaaggctac cgctc tggc gcgggcacaa 26761 gaacgccata gttgettget tgcaagactg tgggggcaac atctccttcg cccgccgctt 26821 tc t: tctct c c tc cggcg tggcct ccc ccgtaacatc ctgcattact accgtcatct 26881 ctacagccca tactgcaccg gcggcagcgg cagcaacagc agcggccaca cagaagcaaa 26941 ggcgaccgga tagcaagact ctgac agc ccaagaaatc c c gcggcg gcagcagcag 27001 gaggaggagc getgegtetg gcgcccaacg aacccgtatc gacccgcgag Cl L 0. 0.0. o. Co.27061 gga t: tttcc cactctgtat get ata c a cagagc g gggccaagaa caagagctga 27121 clelelCelclclclc'ic'i caggtctctg cgatccctca cccgcagctg cctgtatcac aaaagegaag 27181 atcagcttcg gcgcacgctg gaagaegegg aggetetett cagtaaatac tgcgcgctga 27241 ctcttaagga ctagtttcgc gccctttctc aaatttaagc gcgaaaacta cgtcatctcc 27301 agcggccaca cccggcgcca gcacctgttg tcagcgccat tatgagcaag gaaattccca 27361 cgccctacat gtggagttac.. j l *2* tgggacttgc ggctggagct gcccaagact 27421 actcaacccg aataaactac atgagegegg gaccccacat gatatcccgg Cj LCclclCCf clcl 27481 tacgcgccca ccgaaaccga attctcctgg aac.aggcggc tattaccacc acacctcgta 27541 ataaccttaa tccccg L. agt tggcccgctg ccctggtgta ccaggaaagt cccgctccca 27601 ccactgtggt acttcccaga gacgcccagg ccgaagttca gatgactaac tcaggggcgc 27661 agcttgcggg eggetttegt cacagggtgc ggtcgcccgg gcagggtata actcacctga 27721 caa c g gg gegaggtatt cagctcaacg aegagteggt gage tee teg c ggtctcc 27781 gtccggacgg gacatttcag ateggeggeg ccggccgctc ttcattcacg cctcgtcagg 27841 caatcctaac tctgcagacc tcgtcctctg a ccgcgctc gg ggc tt ggaactctgc 27901 a a a 11 g a. ggagtttgtg ccatcggtct actttaaccc etteteggga cctcccggcc 27961 ac ta tccgga t c a a 111 a 11 cctaac g aegeggt ggactcggcg gacggct cg 28021 actgaatgtt aagtggagag gcagagcaac tgcgcctgaa acacctggtc cactgtcgcc 28081 gccacaa tg ctttgcccgc gactccggtg a ttttgct ctttgaattg cccgaggatc 28141 atatcgaggg cccggcgcac ggcgtccggc ttac.c.gccca gggagagett gcccgtagcc 28201 tgattcggga gtttacccag cgccccctgc tagttgagcg ggacagggga ccctgtgttc 28261 tcactgtgat ttgcaactgt cctaaccctg gattacatca agatcctcta gttaatgtca 28321 ggtcgcctaa gtcgattaac tagagtaccc ggggatctta ttccctttaa c L.aai.aa 0.0.0.28381 aaa aa a agc...

Claims

WHAT IS CLAIMED IS:

1. A nucleic acid comprising a codon-altered coding sequence at least 85%, 90%, 95%, 98%, 99% or 100% identical to SEQ ID NO:3 or SEQ ID NO:5, wherein the coding sequence encodes a Norwalk GI.l VPl norovirus protein comprising SEQ ID NO: 9.

2. The nucleic acid of claim 1, comprising a first promoter operably linked to the coding sequence.

3. The nucleic acid of claim 2, wherein the first promoter comprises the CMV promoter or the SV40 promoter.

4. The nucleic acid of claim 2, wherein the first promoter is inducible.

5. The nucleic acid of claim 4, wherein the first promoter comprises a Tet operator.

6. The nucleic acid of claim 1, wherein the nucleic acid is a vector.

7. The nucleic acid of claim 4, wherein the vector is a viral vector,8. The nucleic acid of claim 7, wherein the viral vector is an adenoviral vector.

9. The nucleic acid of claim 8, wherein the adenoviral vector comprises a second promoter operably linked to a nucleic acid encoding a toll-like receptor-3 (TLR-3) agonist.

10. The nucleic acid of claim 9, wherein the TLR-3 agonist is a dsRNA.

11. The nucleic acid of claim 9, wherein the first promoter and the second promoter have different sequences.

12. The nucleic acid of claim 11, wherein the first promoter and second promoter are independently selected from a CMV promoter and an SV40 promoter.

13. The nucleic acid of claim 12, wherein the first promoter comprises a CMV promoter and the second promoter comprises an S V40 promoter.

14. The nucleic acid of claim 13, wherein the CMV promoter comprises a Tet operator, rendering the CMV promoter inducible.

15. A nucleic acid comprising a codon-altered coding sequence at least 85%, 90%, 95%, 98%, 99% or 100% identical to SEQ ID NO: 4 or SEQ ID NO: 6, wherein the coding sequence encodes a Sydney GII.4 VP1 norovirus protein comprising SEQ ID NOTO.

16. The nucleic acid of claim 15, comprising a first promoter operably linked to the coding sequence.

17. The nucleic acid of claim 16, wherein the first promoter comprises the CMV promoter or the SV40 promoter.

18. The nucleic acid of claim 16, wherein the first promoter is inducible.

19. The nucleic acid of claim 18, wherein the first promoter comprises a Tet operator.

20. The nucleic acid of claim 15, wherein the nucleic acid is a vector.

21. The nucleic acid of claim 18, wherein the vector is a viral vector.

22. The nucleic acid of claim 21, wherein the viral vector is an adenoviral vector.

23. The nucleic acid of claim 22, wherein the adenoviral vector comprises a second promoter operably linked to a nucleic acid encoding a toll-like receptor-3 (TLR-3) agonist.

24. The nucleic acid of claim 23, wherein the TLR-3 agonist is a dsRNA.

25. The nucleic acid of claim 23, wherein the first promoter and the second promoter have different sequences.

26. The nucleic acid of claim 25, wherein the first promoter and second promoter are independently selected from a CMV promoter and an SV40 promoter.

27. The nucleic acid of claim 26, wherein the first promoter comprises a CMV promoter and the second promoter comprises an SV40 promoter.

28. The nucleic acid of claim 27, wherein the CMV promoter comprises a let operator, rendering the CMV promoter inducible.

29. A nucleic acid comprising a codon-altered coding sequence at least 85%, 90%, 95%, 98%, 99% or 100% identical to SEQ ID NOV or SEQ ID NO: 8, wherein the coding sequence encodes a GIL 17 VP1 norovirus protein comprising SEQ ID NO: 11.

30. The nucleic acid of claim 29, comprising a first promoter operably linked to the coding sequence.

31. The nucleic acid of claim 30, wherein the first promoter comprises the CMV promoter or the SV40 promoter.

32. The nucleic acid of claim 30, wherein the first promoter is inducible.

33. The nucleic acid of claim 32, wherein the first promoter comprises a Tet operator.

34. The nucleic acid of claim 29, wherein the nucleic acid is a vector.

35. The nucleic acid of claim 32, wherein the vector is a viral vector.

36. The nucleic acid of claim 35, wherein the viral vector is an adenoviral vector.

37. The nucleic acid of claim 36, wherein the adenoviral vector comprises a second promoter operably linked to a nucleic acid encoding a toll-like receptor-3 (TLR-3) agonist.

38. The nucleic acid of claim 37, wherein the TLR-3 agonist is a dsRNA.

39. The nucleic acid of claim 37, wherein the first promoter and the second promoter have different sequences.

40. The nucleic acid of claim 39, wherein the first promoter and second promoter are independently selected from a CMV promoter and an SV40 promoter.

41. The nucleic acid of claim 40, wherein the first promoter comprises a CMV promoter and the second promoter comprises an S V40 promoter.

42. The nucleic acid of claim 41, wherein the CMV promoter comprises a let operator, rendering the CMV promoter inducible.

43. A method for eliciting an immune response towards a Norovirus VP1 protein in a subject, the method comprising administering to the subject an immunogemcally effective amount of one or more of the nucleic acids of claim 1, 15, or 29 to a mammalian subject.

44. The method of claim 43, wherein the administering is oral, intranasal, or mucosal.

45. The method of claim 44, wherein the administering is oral deh very by swallowing a tablet or capsule.

46. The method of claim 43, wherein the method comprises administering to the mammalian subject an immunogemcally effective amount of two nucleic acids of claim 1, 15, or 29.

47. The method of claim 43, wherein the method comprises administering to the mammalian subject an immunogemcally effective amount of three nucleic acids of claim 1, 15, or 29.

48. The method of claim 43, wherein the immune response is elicited in an alveolar cell, an absorptive enterocyte, a ciliated cell, a goblet cell, a club cell, a dendritic cell, a macrophage, and / or an airway basal cell of the subject.

49. The method of claim 43, wherein the subject is a human.

50. A pharmaceutical composition comprising one or more vectors of claim 6, 20, or 34.

51. The pharmaceutical composition of claim 50, wherein the pharmaceutical composition is a tablet or a capsule.

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