CN1461805A - Structure of recombination herpes simplex virus and its use - Google Patents

Abstract

A recombinant type (type-1) of 5 herpes simplex virus (rHSVS) is disclosed, whose genoms are respectived inserted by adeno-associated virus serum type-2 (AAV2) rep gene and the cap genes of AAV1, AAV3, AAV4, AAV5 and AAV6. After they are used to infect cells, the associated recombinant AAV carries (rAAVs) can be obtained. Its advantages are high efficiency and no need of reconfiguration.

Description

Structure of one group of recombinant herpes simplex virus and uses thereof

The invention belongs to the biotechnology invention field.Be specifically related to 5 strain recombinant herpes simplex virus (Herpes Simplex Virus, construction process HSV) and purposes.

Background introduction

Gene therapy is a kind of brand-new disease treatment pattern that grows up the 1980s, and it is different from traditional pharmacological agent, but will produce the gene importing human body of medicine, with correcting defect gene or performance therapeutic action.Compare with traditional therapy, the advantage of gene therapy is significantly, and its single administration is permanently effective, and the state of nature of more expressing near human body gene, and is therefore safer, more effective.According to statistics, end to calendar year 2001, nearly 600 of the gene therapy clinical protocol that the whole world has been passed through, treatment target mainly is that human health is threatened serious disease, as inherited disease, tumour, transmissible disease and various metabolic diseases etc., have above 3400 people and accepted this therapy.

The key issue of gene therapy is to find therapeutic gene safety is effectively imported human body, and makes the approach of therapeutic gene long-term expression.Usually the method that adopts has physical method and biological method.

Physical method be by calcium phosphate, electricity commentaries on classics, liposome etc. with the therapeutic gene transfered cell, this method security is good, but efficient is low, is in experimental study usually.

Biological method is to use the organism that human body is had the natural infection ability, mainly be virus as carrier, by gene recombination technology therapeutic gene is assembled in the virus vector, the infection by virus imports human body with therapeutic gene.The transduction efficiency height of virus vector, present most gene therapy schemes all are to adopt this method.(Morgan，R.A.and?W.F.Anderson，Annu.Rev.Biochem.62：191-217，1993).

Virus carrier system

Present existing virus vector mainly contains retroviral vector, adenovirus carrier, gland relevant viral vector, herpes simplex virus vector etc.

Retroviral vector once was to use maximum virus vector, and this is because retroviral vector can insert therapeutic gene the karyomit(e) of human body cell and stably divide with the division of cell, and therapeutic gene is stablized and lasting the expression.But, there is the danger that destroys human body normal gene function because its insertion is at random.

The adenovirus carrier gene does not insert human chromosome, and the cell category that can infect is also many than retrovirus, but because therapeutic gene does not insert karyomit(e), so need repeatedly medication repeatedly, and unfortunately adenovirus has very strong immunogenicity, in human body, repeatedly use the expression that can activate neutralizing antibody, and reduce result of treatment.Therefore, adenovirus carrier is limited at patient's access times on one's body.

Herpes simplex virus vector has the transduction efficiency height, can infect division and Unseparated Cell, can therefore application promise in clinical practice be arranged against characteristics such as aixs cylinder conduction in neural system in neural system.What limit its application at present mainly is that it has neurotoxicity, therefore also is in conceptual phase.

The AAV virus vector

Adeno-associated virus (AAV) has obtained development faster in recent years as being applied in of gene therapy vector.AAV can infect multiple mammalian cell or the tissue that comprises the people with higher titre, and can be in human body cell site-directed integration (it is long-armed to be arranged in No. 19 karyomit(e)) (Kotin, R.M., et al., Proc.Natl.Acad.Sci.USA 87:2211-2215,1990) (Samulski, R.J., et al., EMBO J.10:3941-3950,1991), thus the long-term stability that had both realized therapeutic gene express, reduced again and inserted the risk of bringing that makes the chromogene sudden change at random.And, AAV does not find and any human disease-related so far, also do not find anyly owing to the change of integrating the biological character cause, so security is significantly better than retroviral vector and adenovirus carrier, and the latter is relevant with respiratory tract disease respectively at the mankind's cancer.

The AAV virus vector has overcome the deficiency of other several virus vector, has therefore obtained significant progress in recent years.But the AAV virus vector is also demanded improved place urgently.

At present general AAV virus vector all is based on serotype 2, i.e. AAV2 is to the existing nearly 30 years history of its research.Experimental results show that reorganization AAV2 (rAAV2) is good gene transfer vector (Monahan in multiple tissue, Pand R.Samulski, 2000, Gene Ther.7:24-30), but along with the increase of testing in its body, the also more and more obvious (Bartlett of the limitation of rAAV2 carrier, J.S., R.Wilcher, and R.J.Samulski.2000.J.Virol.74:2777-2785.) (Davidson, B., C.Stein, J.Heth, et al.2000.Proc.Natl.Acad.Sci.USA 97:3428-3432.): AAV2 efficiency of infection in some tissue is very high, and the efficiency of infection in other tissues is very low; In addition, human body can produce neutralizing antibody to the infection of AAV, in normal population, have 85% exist at various AAV, mainly be antibody at AAV2.

In order further to improve the efficiency of infection and the host range of AAV virus vector, the scientific research personnel has carried out multiple trial, such as being with bifunctional antibody (Bartlett on the nucleocapsid of AAV virus vector, J.S., J.Kleinschmidt, R.S.Boucher, and R.J.Samulski.1999.Nat.Biotechnol.17:181-186.), mutagenesis screening nucleocapsid protein (Girod, A., M.Ried, C.Wobus, et al.1999.Nat.Med.5:1052-1056.) (Wu, P., W.Xiao, T.Conlon, J.Hughes, et al.2000.J.Virol.74:8635-8647.) method such as, and obtained certain effect.People concentrated on sight in the tissue-specific research to the AAV virus vector of various serotypes in recent years, utilized the natural infection characteristic of each serotype of AAV, can obtain various tissues are had the AAV virus vector of different transduction efficiencies.(Chao，H.，Y.Liu，J.Rabinowitz，C.Li，R.J.Samulski，et?al.2000.Mol.Ther.2：619-623.)(Chiorini，J.，L.Yang，Y.Liu，B.Safer，and?R.Kotin.1999.J.Virol.73：1?309-1319.)(Chiorini，J.A.，B.Zimmermann，L.Yang，R.et?al.1998.Mol.Cell.Biol.18：5921-5929.)

AAV virus and genome structure

AAV virus is little, the nonencapsulated virus of a class volume, includes single stranded DNA, and wherein the quantity of normal chain and minus strand is equal substantially.AAV virus belongs to microvirus and belongs to (Parvoviridae), it duplicate the existence that needs helper virus.(Kotin, RM.1994.Hum.Gene Ther.5:793-801) the primates AAV virus of bibliographical information at present has six kinds of serotypes, is named as AAVl, AAV2, AAV3, AAV4, AAV5, AAV6 respectively.(Baclunann PA, MD.Hoggan, JL.Melnick, 1975, Parvoviridae, Intervirology 5:83-92) (Bantel-Schaal U., and H.zur Hausen.1998.Virology 134:52-63) (Rutledge.EA., CL.Halbert, and DW.Russell.1998.J.Virol.72:309-319) up to the present, AAV1,2,3,4,5,6 complete sequence are clear, and the genomic homology of various serotypes is between 52-82%.(Bantel-Schaal?U.，and?H.zur?Hausen.J.Virol.1999，73：939-947)

AAV research is clear that AAV2, its genome are the single stranded DNAs (Laughlin, C.A., J.D.Tratschin, H.Coon, and B.J.Carter.1983.Gene 23:65-73) of long 4680bp most.The genome two ends be " oppositely terminal repeat " (ITR), it has the meander structure of interruption in the middle of being, forms hairpin structure to stablize the strand genome.Have in the genome and have only two great openings to read frame (ORF), (SrivastavaAE., Lusby and KI.Bems.1983.J.Virol.45:555-564), they are respectively rep and cap gene.

AAV2 genome left side is the rep gene, it the coding AAV Nonstructural Protein Rep, initial by p5 and p19 promotor respectively, obtain respectively separately through cutting with without the mRNA transcription product that cuts, thereby obtain four kinds of albumen: Rep78, Rep68, Rep52 and Rep40.The proteic effect of Rep is transcribing of control AAV, participates in AAV and duplicates, and play an important role in the assembling of genomic generation of filial generation and virion.Wherein unwind site trs (terminal resolution site) and GAGY tumor-necrosis factor glycoproteins epi-position (repeat motif) specificity of Rep78 and Rep68 and the end of ITR kind combines, and starts the AAV genome by the reproduction process of strand to two strands.(Chiorini, J.A., S.M.Wiener, R.M.Kotin, R.A.Owens, and B.Safer.1994.J.Virol.68:7448-7457) Rep combines with DNA and end is separated the process that chain process also is the long-armed AAVSl site of No. 19 karyomit(e)s of AAV genome fixed point insertion.(Kotin, R.M., J.C.Menninger, D.C.Ward, and K.I.Berns.1991.Genomics 10:831-834) trs and GAGC tumor-necrosis factor glycoproteins epi-position are the centers of AAV genome duplication among the ITR, though therefore the ITR sequence all is not quite similar in the AAV of various serotypes virus, can both constitutes hairpin structure and have Rep binding site (such as the GAGY of AAV2) and trs.Also have two other rep gene at rep78, rep68 downstream figure spectral position 19 places, express Rep52 and Rep40 respectively, their promotor is p19.Rep52 and Rep40 do not have the function in conjunction with DNA, and the dna helicase activity that has ATP to rely on.(Smith, R., andR.M.Kotin.1998.J.Virol.72:4874-4881) the proteic conservative degree of Rep is higher in AAV1,2,3,4,6, wherein the homology of Rep78 in above-mentioned virus reaches 89-93% (Chiorini JA., L.Yang, Y.Liu, and RM.Kotin.1997.J.Virol.71:6823-6833.Muramatsu.SI.H.Mizuka mi, NS.Young and KE.Brown.1996.Virology 221:208-217)

The genomic right-hand part of AAV is the cap gene, the latter encode nucleocapsid protein VP1, VP2 and VP3.Wherein, VP3 molecular weight minimum, but quantity is maximum, VP1 molecular weight maximum but minimum number, the ratio of VP1, VP2, VP3 is 1: 1: 20 in sophisticated AAV particle.VP1 is that to be formed with infective AAV necessary; VP2 assists VP3 to enter nucleus; VP3 forms AAV particulate major protein (Muzyczka.N.1992.Curr.Top.Microbiol.Immunol.158:97-129).Different with Rep, the conservative degree of Cap albumen in various serotype A AV is lower, and this is different host ranges of having of different serotypes AAV and specific major cause.

The homology of various serotype A AV viruses relatively

The primates AAV virus of bibliographical information has six kinds of serotypes, is named as serotype 1,2,3,4,5,6 respectively.Wherein have only AAV5 from human body, to separate (Bantel-Schaal at first, and H.zur Hausen.1984.Virology 134:52-63), the AAV virus of all the other 5 kinds of serotypes is all found (UrsulaBantel-Schaal when the research adenovirus, Hajo Delius and Harald zur Hausen.J.Virol.1999,73:939-947).Up to the present, the complete sequence of the AAV virus of whole 6 kinds of serotypes is all clear, (John Chiorini, Frank Kim, Linda Yang, and Robert Kotin.J.Virol.1999,73:1309-1319), except that AAV5, AAV1,2,3,4, the genomic homology of 6 serotypes are generally higher, particularly ITR and Rep zone, and wherein the homology of Rep in AAV1,2,3,4,6 is up to 89-93%, therefore Rep can discern ITR from another serotype between AAV1,2,3,4,6 serotypes, and supports its packing.(Chiorini?J，L.Yang，Y.Liu，B.Safer，and?M.Kotin.1997.J.Virol.71：6823-6833)(Muramatsu，S.，H.Mizukami，N.Young，and?K.Brown.1996.Virology221：208-217)。And the homology of the Rep of AAV5 and other AAV serotype has only 67% (Ursula Bantel-Schaal, Hajo Delius and Harald zur Hausen.J.Virol.1999,73:939-947) (John Chiorini, Frank Kim, Linda Yang, and Robert Kotin.J.Virol.1999,73:1309-1319), so the Rep of AAV5 can not discern the ITR of other serotype A AV.

The cell receptor of AAV virus

Compare with Rep, the homology of the Cap of each serotype of AAV is lower, the amino acid identity of the Cap of AAV1, AAV2, AAV3, AAV5, AAV4, AAV6 is between 45～80%, and wherein the homology between AAV1 and the AAV6 is the highest, and the homology of the Cap of AAV5 and other serotype is minimum.(Ursula?Bantel-Schaal，Hajo?Delius?and?Harald?zur?Hausen.J.Virol.1999，73：939-947)。This is the basis that each serotype has different host ranges and cell-specific.The host range of AAV virus and cell-specific are by the kind of corresponding acceptor on the cell of its infection and how many decisions.Acceptor research at present is clear that serotypes such as AAV2, AAV3, AAV4, AAV5.The cell receptor of AAV2, AAV3 serotype is heparin sulfate glycoprotein (heparan sulfate proteoglycan), and its receptor binding site is positioned on the VP3 albumen of AAV2.Its co-receptor (coreceptor, function is to help AAV virus to enter cell) is human desmocyte growth factor receptors 1 (fibroblast growth factor receptor 1) and integrin alpha v beta 5.(Qing，K.，C.Mah，J.Hansen，S.Zhou，V.Dwarki，and?A.Srivastava.1999.Nat.Med.5：71-77)(Summerford，C.，J.S.Bartlett，and?R.J.Samulski.1999.Nat.Med.5：78-82)。The cell receptor of AAV4, AAV5 is sialic acid (sialic acid) (WaltersRW, Yi SM, Keshavjee S, Brown KE, et al.J Biol Chem 2001 276:20610-6), does not have the heparin sulfate binding site, therefore the cell-specific of AAV5 and AAV2 etc. have very big difference, especially show AAV5 at the efficiency of infection of animal and human's neural system and airway epithelial than AAV2 much higher (AAV4 does not infect airway epithelial).

Existing AAV2 carrier is carried out " changing shell " transform (structure of heterozygosis AAV virus vector)

Existing AAV2 carrier being carried out " changing shell " transform, is the simplest and the most direct approach of AAV virus vector that obtains the close preferendum of cell of other the 5 kinds of AAV serotypes except that AAV2.Experimentation on animals finds that compare with the AAV2 carrier, AAV1 is at its hetero-organization except that nervous tissue, and is all generally higher such as the transduction efficiency in muscle tissue and the liver; (Jianming Wang et al.2001.Diabetes has better efficiency of infection in 50:515-520) for Terence Flotte, Anupam agarwal and AAV5 is at retina, brain and pancreas islet.Wherein AAV1 to the efficiency of infection of muscle tissue than the high 100-1000 of AAV2 doubly.(76:791-801) order of AAV efficiency of infection serotype from high to low in liver and muscle tissue is 1,5,3,2,4 for Joseph E.Rabinowitz Fabienne Rolling Chengwen, 2002.J.Virol; The order of the serotype in rat retina is 5,4,1,2,3.In a word, will obtain to have the AAV virus vector of different infection characterizations, expand the Application Areas of AAV virus vector at different cell types to the research of each serotype beyond the AAV2.

Not only height homology but also distinguishing characteristic between the genome of each serotype of AAV make us carry out " changing shell " to our existing AAV2 carrier with comparalive ease and transform.Promptly do not change when having AAV virus vector cis element ITR (from AAV2) now, by changing the coat protein Cap of each AAV serotype, obtain to have AAV1, AAV3 respectively, the heterozygosis AAV virus vector of AAV4, AAV5, AAV6 serotype cell parent preferendum (ITR from AAV2, shell respectively from AAV1, AAV3, AAV4, AAV5 and AAV6).Wherein the homology of AAV1, AAV3, AAV4, AAV6 and AAV2 is higher, does not change the Rep of AAV2 as long as change Cap, just can transly pack out corresponding shell from AAV1, AAV3, AAV4, AAV5 or AAV6, and ITR is from the AAV heterozygosis carrier of AAV2.But AAV5 is more special, because the homology of AAV5 and AAV2 is lower, can not supports fully from the Rep albumen of AAV2 that AAV5 is genomic and duplicate and pack, so need to replace with the Rep gene of part A AV5 the Rep of AAV2.According to bibliographical information, preceding 232 amino acid (about 700bp) of the rep of AAV2 are the necessary (Yoon of ITR that Rep albumen is correctly discerned AAV2, M, D.Smith, P.Ward, et al.J.Virol.75:3230-3239), therefore make up preceding 232 amino acid that AAV2/5 heterozygosis carrier at least also will keep AAV2.Report is arranged, pack helper plasmid and contain the packaging plasmid cotransfection cell of two ITR of AAV2 from what AAV5 formed, can obtain the AAV2/5 heterozygosis carrier of function with preceding 250 amino acid, remaining Rep and the Cap of the Rep of AAV2.(Joseph?E.Rabinowitz，FabienneRolling，et?al.J.Virol.2002，76：791-801)

The production method of AAV virus vector

The genome of AAV-2 is a linear ssdna, the about 4800bp of total length, its two ends contain the long reversing terminal repeat of 2 each 145bp (Inverted terminal repeat, ITR), they are the genomic replication orgin of AAV, and duplicate, integrate with AAV or function such as packing relevant.Its genome rest part can be divided into 2 functional zone, rep gene regions and cap gene regions.The rep gene has the product of 4 kinds of different forms: Rep78, Rep68, Rep52, Rep40.They duplicate and necessary adjusting albumen such as viral gene expression for AAV.3 kinds of structural protein of cap genes encoding, VP1, VP2, VP3, mutual group is dressed up the shell of AAV virus.The albumen of rep and cap genes encoding all is trans-acting albumen in the AAV toxigenicity is duplicated.Therefore, under the situation that does not change ITR, as long as change the cap albumen of various serotype A AV, just can obtain having the heterozygosis AAV virus vector of the infection characteristic of each serotype, promptly can continue to use the carrier cell strain that has various therapeutic genes and marker gene in a large number, thereby simplify the process that the AAV virus vector " changes shell " greatly for packing AAV2 vector construction.

The classical way that produces rAAV virus is for importing rAAV virus vector plasmid and the helper plasmid that contains the rep-cap gene in the cell of adenovirus or herpes simplex infections.From the cell of culture supernatant and pathology, can gather in the crops reorganization AAV virus (rAAV) after 2-3 days, also contain used adenovirus or hsv simultaneously.Adenovirus and hsv all available heat are handled (55 ℃ 30 minutes to 2 hours) and deactivation, but do not influence the activity of AAV virus.

Though the method for this production rAAV virus is fairly simple, but still has many significant disadvantages.All need transfectional cell when preparing rAAV virus at first, at every turn.Because the restriction of transfection method self, transfection and cotransfection efficient are lower, are to produce one of lower reason of rAAV virus titer.And, also be difficult to extensive transducer cell at present with transfection method, so the needs of incompatibility mass production rAAV virus.Therefore, be necessary to study a kind of system and method that can be used for mass production rAAV virus.

The patent of invention of Yan Ziying etc. 1996 applications once " can be used to herpes simplex virus vector of packing recombinant adeno-associated virus and uses thereof " by name (Chinese patent application number 96120549.0, publication number CN 1159480A).This patent has been introduced a kind of rep-cap gene with AAV2 and has been placed HSV1 amplicon vector plasmid, is built into pHSV-AAV (+/-).In this plasmid transfered cell, in the presence of the HSV1 wild-type virus, can obtain a kind of wild-type HSV1 and the hybrid virus that contains the pseudovirus of rep-cap gene, this hybrid virus has whole subsidiary functions that rAAV virus system and packing are provided.(Conway JE et al, J.Virol.71:8780-8789,1997) such as nearest Conway have also reported similar research.But, the shared ratio less (＜10%) of pseudovirus in this hybrid virus, the subsidiary function that can provide is limited; And the ratio of pseudovirus and wild-type virus is unfixing in viral crossing, is unfavorable for mass-produced quality control.

Wu Xiaobing etc. place the HSV1 genome with the rep-cap gene of AAV2, are built into to be used for easy and global function helper virus HSV-rc mass production rAAV virus.(Wu Xiaobing etc. are used for generation of the global function helper virus that recombinant adeno-associated virus produces and uses thereof, Chinese patent application number 98120033.8).Infect the cell of rAAV virus vector plasmid transfection or stablize the cell strain that carries rAAV virus vector plasmid with HSV-rc, just can produce has infective rAAV virion in a large number.The rAAV of Chan Shenging can import foreign gene in the mammalian cell and express in this way.(Wu Zhijian, Wu Xiaobing etc., Science Bulletin.1999，44(5)：506-509。Wu Zhijian, Wu Xiaobing etc., Chinese science C collects.2001，31(5)：423-430。WU?Zhijian，WU?Xiaobing，et?al.Science?in?China(Series?C).2002，45(1)：96-104。WU?Zhijian，WU?Xiaobing，et?al.Chinese?Science?Bulletin。1999，44(8)：715-718。)

Content of the present invention

What this patent was described is that one group of (totally 5 strains) recombinant herpes simplex virus (is respectively HSV-r2c1, HSV-r2c3, HSV-r2c4, HSV-r2c5, HSV-r2c6), rep gene and the serotype 1 (AAV1) of adeno-associated virus (AAV) serotype 2 (AAV2) have been inserted in their genomes respectively, 3 (AAV3), 4 (AAV4), the cap gene of 5 (AAV5) 6 (AAV6), that is: obtain recombinant herpes simplex virus HSV-r2c1 with the rep gene of AAV2 and the cap assortment of genes of AAV1, obtain recombinant herpes simplex virus HSV-r2c3 with the rep gene of AAV2 and the cap assortment of genes of AAV3, obtain recombinant herpes simplex virus HSV-r2c4 with the rep gene of AAV2 and the cap assortment of genes of AAV4, obtain recombinant herpes simplex virus HSV-r2c5 with the rep gene of AAV2 and the cap assortment of genes of AAV5, obtain recombinant herpes simplex virus HSV-r2c6 with the rep gene of AAV2 and the cap assortment of genes of AAV6.With these recombinant herpes simplex virus cells infected respectively, infected cells can be expressed the Rep albumen of AAV2 and express AAV1,3,4,5,6 Cap albumen respectively.With these recombinant herpes simplex virus (HSV-r2c1, HSV-r2c3, HSV-r2c4, HSV-r2c5, HSV-r2c6) as helper virus, infection contains the gene order of ITR and the foreign gene of AAV2, and (cell strain of ITR-foreign gene-ITR) can produce the reorganization AAV virus vector (rAAVs) with 1,3,4,5,6 serotype A AV shells respectively.The capsid protein Cap of different sorts AAV has determined tissue specificity and the efficiency of infection of AAV, by using the capsid protein of a certain serotype instead, can obtain efficiently to infect the rAAV virus vector of some tissue, thereby improve validity and the security of rAAV virus vector in gene therapy.

The accompanying drawing summary

Accompanying drawing 1:rep2cap1 collection of illustrative plates.The rep gene is based on the rep gene (being about 1721bp) of AAV2, and 3 ' end contains a bit of rep (being about 280bp) from AAV1.The cap gene is fully from AAV1 (being about 2210bp).

Accompanying drawing 2:rep2cap3 collection of illustrative plates.The rep gene is fully from AAV2; The cap genetic protosome is from AAV3 (being about 2040bp), and 5 ' end is a bit of from AAV2 (being about 30bp).

Accompanying drawing 3:rep2cap4 collection of illustrative plates.The rep genetic protosome is from AAV2 (being about 1721bp), and 3 ' end is a bit of from AAV4 (being about 280bp); The cap genetic protosome is from AAV4 (being about 2170bp), and 3 ' end is a bit of from AAV2 (being about 160bp).

Accompanying drawing 4:rep2cap5 collection of illustrative plates.The rep gene 5 ' is brought in from AAV2 (being about 860bp), and 3 ' brings in from AAV5 (being about 1122bp); The cap gene is fully from AAV5 (being about 2170bp).

Accompanying drawing 5:rep2cap6 collection of illustrative plates.The rep genetic protosome is from AAV2 (being about 1721bp), and 3 ' end is a bit of from AAV6 (being about 280bp); The cap gene is fully from AAV6 (being about 2210bp).

Accompanying drawing 6:cos6-rXcY Δ UL2 collection of illustrative plates.Wherein rXcY is respectively r2c1, r2c3, r2c4, r2c5, r2c6.The gene direction is not limit.

Accompanying drawing 7:cos56-rXcY Δ UL44 collection of illustrative plates.Wherein rXcY is respectively r2c1, r2c3, r2c4, r2c5, r2c6.The gene direction is not limit.

Accompanying drawing 8:Set C collection of illustrative plates.Cos6, cos28, cos14, cos56, cos48 form Set C, and after the latter cut the cos skeleton with Pac I, transfectional cell obtained HSV1 virus through homologous recombination.One each Xba I site is wherein respectively arranged in the UL44 gene of the UL2 gene of the HSV1 of cos6, the HSV1 on the cos56, be used to insert foreign gene.

Accompanying drawing 9:pSNAV-GFP collection of illustrative plates.GFP (green fluorescent protein) gene is started by the immediate early promoter of people CMV virus, and polyA is from SV40 virus.GFP expression cassette two ends are ITR (oppositely terminal repetition) of AAV2.Reorganization HSV virus with the present invention's proposition: HSV-r2c1, HSV-r2c3, HSV-r2c4, HSV-r2c5, HSV-r2c6 infect the cell strain of transfection pSNAV-GFP respectively, 5 kinds of AAV virus vector that can obtain having AAV1,3,4,5,6 serotype capsid proteins respectively and can express reporter gene GFP.

The present invention utilizes above-mentioned Wu dogface wait to build the same principle of HSV-rc, and (Wu Xiaobing etc., be used for generation of the global function helper virus that recombinant adeno-associated virus produces and uses thereof, Chinese patent application numbers 98120033.8. Wu Zhijian, Wu Xiaobing etc., Science Bulletin. 1999,44 (5): 506-509. Wu Zhijian, Wu Xiaobing etc., Chinese science C collects. 2001,31 (5): 423-430. WU Zhijian, WU Xiaobing, et al.Science in China (Series C) .2002,45 (1): 96-104. WU Zhijian, WU Xiaobing, et al.Chinese Science Bulletin. 1999,44 (8): 715-718. ), on our existing basis with the Full Featured helper virus of AAV2,, by the genetic modification to HSV-rc, obtain having respectively serotype 1,3,4,5, the helper virus of 6 AAV viral vectors production function. It is characterized in that having inserted in the HSV1 genome copy, respectively from the rep-cap gene of AAV2 (rep) and AAV1,3,4,5,6 (cap) (approximately 4kb, direction does not limit). In the constructed 5 strain recombinant herpes simplex virus of the present invention, the rep-cap gene is inserted in respectively in the XbaI site of HSV1 UL2 gene (coding uracil dna glycosylase) or HSV1 UL44 gene (coding gC), or with the method for homologous recombination, inserts genomic other dispensable gene district of HSV1. Dispensable gene refers to for HSV1 the propagation in cultured cell in vitro and goes down to posterity is nonessential, is about to foreign gene and inserts normal replication and the breeding that can not affect HSV1 virus in these dispensable genes. These restructuring HSV1 virus all can be bred and stable going down to posterity in HSV1 sensitive cells (as BHK-21). 5 constructed strain herpes simplex virus of the present invention infect respectively cell or the stable cell line that carries rAAV viral vectors plasmid of rAAV viral vectors plasmid transfection, can produce the infective rAAV virion that has that contains respectively AAV1,3,4,5,6 nucleocapsid.

The generation of 5 strain recombinant herpes simplex virus is to realize a cover being contained on the basis that the complete genomic cosmid Set C clay of HSV1 virus (comprise cos6, cos14, cos28, cos48, cos56 be totally 5 clays) transforms.

The present invention links to each other AAV1,3,4,5,6 cap gene respectively with the rep gene of AAV2, become rep2cap1, rep2cap3, rep2cap4, rep2cap5, rep2cap6 dna fragmentation (seeing accompanying drawing 1,2,3,4,5 respectively).Wherein in the dna fragmentation of rep2cap5, rep2 is that the part by the rep gene of the part of the rep gene of AAV5 and AAV2 merges the heterozygosis rep gene that forms, that is, this rep2 is the heterozygous genes of part rep5 and part rep2.These 5 dna fragmentations are respectively charged in the HSV1 genome, obtain to express AAV1 respectively, 3,4,5,6 cap egg is from the proteic 5 strains reorganization of the rep that also expresses AAV2 simultaneously HSV1:HSV-r2c1 (expressing the cap albumen of AAV1 and the rep albumen of AAV2 simultaneously), HSV-r2c3 (expressing the cap albumen of AAV3 and the rep albumen of AAV2 simultaneously), HSV-r2c4 (expressing the cap albumen of AAV4 and the rep albumen of AAV2 simultaneously), HSV-r2c5 (expresses cap albumen and the AAV2 of AAV5 simultaneously, 5 heterozygosis rep albumen), HSV-r2c6 (expressing the cap albumen of AAV6 and the rep albumen of AAV2 simultaneously).Infect the cell or the stable cell strain that carries rAAV virus vector plasmid of rAAV virus vector plasmid transfection respectively with them, just can produce the infective rAAV virion that has that contains AAV1,3,4,5,6 nucleocapsid respectively.

Feature description to above-mentioned 5 strain recombinant herpes simplex virus (being commonly referred to as HSV-rXcY) is as follows:

(1)HSV-r2c1：

A kind of recombinant herpes simplex virus (HSV) is characterized in that having inserted in its genome a kind of dna sequence dna, and it has the nucleotide sequence shown in the SEQ ID NO.1 or its homologous sequence.Wherein dna sequence dna SEQ ID NO.1 is inserted in the xbaI site of the genomic UL2 gene of HSV.

In addition, the XbaI site of the UL44 gene that dna sequence dna SEQ ID NO.1 also can be by inserting HSV1 or with other dispensable gene district of the method insertion HSV1 of homologous recombination.Such as the dispensable gene tk that substitutes HSV1 with the homology arm method with SEQ ID NO.1.

(2)HSV-r2c3：

A kind of recombinant herpes simplex virus (HSV) is characterized in that having inserted in its genome a kind of dna sequence dna, and it has the nucleotide sequence shown in the SEQ ID NO.2 or its homologous sequence.Wherein dna sequence dna SEQ ID NO.2 is inserted in the xbaI site of the genomic UL2 gene of HSV.

In addition, the XbaI site of the UL44 gene that dna sequence dna SEQ ID NO.2 also can be by inserting HSV1 or with other dispensable gene district of the method insertion HSV1 of homologous recombination.Such as the dispensable gene tk that substitutes HSV1 with the homology arm method with SEQ ID NO.2.

(3)HSV-r2c4：

A kind of recombinant herpes simplex virus (HSV) is characterized in that having inserted in its genome a kind of dna sequence dna, and it has the nucleotide sequence shown in the SEQ ID NO.3 or its homologous sequence.Wherein dna sequence dna SEQ ID NO.3 is inserted in the xbaI site of the genomic UL2 gene of HSV.

In addition, the XbaI site of the UL44 gene that dna sequence dna SEQ ID NO.3 also can be by inserting HSV1 or with other dispensable gene district of the method insertion HSV1 of homologous recombination.Such as the dispensable gene tk that substitutes HSV1 with the homology arm method with SEQ ID NO.3.

(4)HSV-r2c5：

A kind of recombinant herpes simplex virus (HSV) is characterized in that having inserted in its genome a kind of dna sequence dna, and it has the nucleotide sequence shown in the SEQ ID NO.4 or its homologous sequence.Wherein dna sequence dna SEQ ID NO.4 is inserted in the xbaI site of the genomic UL2 gene of HSV.

In addition, the XbaI site of the UL44 gene that dna sequence dna SEQ ID NO.4 also can be by inserting HSV1 or with other dispensable gene district of the method insertion HSV1 of homologous recombination.Such as the dispensable gene tk that substitutes HSV1 with the homology arm method with SEQ ID NO.4.

(5)HSV-r2c6：

A kind of recombinant herpes simplex virus (HSV) is characterized in that having inserted in its genome a kind of dna sequence dna, and it has the nucleotide sequence shown in the SEQ ID NO.5 or its homologous sequence.Wherein dna sequence dna SEQ ID NO.5 is inserted in the xbaI site of the genomic UL2 gene of HSV.

In addition, the XbaI site of the UL44 gene that dna sequence dna SEQ ID NO.5 also can be by inserting HSV1 or with other dispensable gene district of the method insertion HSV1 of homologous recombination.Such as the dispensable gene tk that substitutes HSV1 with the homology arm method with SEQ ID NO.5.

The present invention proposes the preparation method of 5 strain recombinant herpes simplex virus, this method comprises that structure contains SEQ ID NO.1, SEQ ID NO.2, SEQ ID NO.3, the dna fragmentation of SEQ ID NO.4 or SEQ ID NO.5, and utilize engineered method that this dna fragmentation is inserted in the genome of hsv, thereby obtain the hsv of reorganization.Perhaps insert and SEQ ID NO.1, SEQ ID NO.2, SEQ ID NO.3, other dna sequence dna of dna fragmentation homologous of SEQ ID NO.4 or SEQ ID NO.5 obtains the identical recombinant herpes simplex virus of function.Simultaneously, the present invention proposes the purposes of this 5 strain recombinant herpes simplex virus.

The present invention is used to make up the primeval life material of 5 strain recombinant herpes simplex virus

Set C clay: by load sharing successively complete genomic 5 clays of HSV1 virus form: cos6, cos14 cos28, cos48, cos56.For Davision AJ give (Conningham C, Davision AJ.Virology, 1993,197:116-124).(cos6, cos14 cos28, cos48, the sequence of cos56 is seen Seq6, Seq7, Seq8, Seq9, Seq10 respectively).The segmental end of each HSV1 viral genome that loads in this cover clay repeats with being loaded into the segmental end sequence of HSV1 in another clay, thereby be 5 HSV1 genomic fragments the basis (seeing accompanying drawing 8) that homologous recombination produces the HSV1 that recombinates takes place in cell for this.The single point of contact of an XbaI is respectively arranged among the dispensable gene UL2 of the last HSV1 of cos6 among the Set C and cos56 and the UL44, be used for foreign gene is inserted wherein, and produce the reorganization HSV virus of having inserted foreign gene by 5 clays reorganization.

AAV1, AAV3, AAV4 background: ATCC numbering are respectively ATCC VR645, ATCC VR681, ATCCVR646.

The AAV5 virus strain: document is seen in the source.(Bantel-Schaal?U，Zur?Hausen?H.Virology?1984，134：52-63)

The AAV6 virus strain: document is seen in the source.(Rutledge，E.A.，Halbert，C.L.and?Russell，D.W.J.Virol.1998，72：309-319)

SSV9: contain the rep of AAV2 and the plasmid of cap gene.(Du?B，Wu?P，Boldt-Houle?DM，TerwilligerEF?Gene?Ther?1996，3：254-61)

The patent relevant with the present invention

Wu Xiaobing etc. are fundamental construction recombinant herpes simplex virus and uses thereof with the clay, Chinese patent application number 98101753.3 (open);

Wu Xiaobing etc. are used for generation of the global function helper virus that recombinant adeno-associated virus produces and uses thereof, Chinese patent application number 98120033.8 (open).

The preparation method of 5 strain recombinant herpes simplex virus

Adopt and preparation essentially identical strategy of HSV1-lacZ100 recombinant virus and method.The latter inserts the lacz gene in the XbaI site of cos6, and by the method that 5 clays are recombinated, has obtained the HSV1-lacZ100 recombinant virus.(Wu Xiaobing etc. are fundamental construction recombinant herpes simplex virus and uses thereof with the clay, Chinese patent application number 98101753.3)

Rep (AAV2) and cap (AAV1, AAV3, AAV4, AAV5, AAV6) gene is used downstream primer respectively from separately viral genome template, after the PCR method acquisition, the method that adopts restriction enzyme to cut, connect again obtains corresponding r2c1, r2c3, r2c4, r2c5 and r2c6 gene fragment respectively, and the two ends of these gene fragments all are XbaI site (seeing accompanying drawing 1,2,3,4,5).

In the r2c5 gene fragment, rep2 merges the heterozygosis rep gene that forms by the part of the rep gene of the part of the rep gene of AAV5 and AAV2, that is, this rep2 is the heterozygous genes of part rep5 and part rep2.Its preparation is: a pair of primer of the rep of usefulness AAV2 is from AAV2 viral genome template, obtain the part of rep2 by PCR method, with a pair of primer of the rep of AAV5 from AAV5 viral genome template, by another part of PCR method acquisition rep5, the method that adopts restriction enzyme to cut, connect again obtains this heterozygosis rep gene that contains part rep5 and part rep2.

An XbaI single endonuclease digestion site is respectively arranged in the HSV1 genomic fragment of the loading in cos6 and the cos56 clay, lay respectively in dispensable gene UL2 and the UL44, can be used for inserting foreign gene usually.To insert respectively in the XbaI site of cos6 through r2c1, r2c3, r2c4, r2c5 and the r2c6 gene fragment of XbaI enzyme cutting, be built into reorganization clay cos6-r2c1 Δ UL2, cos6-r2c3 Δ UL2, cos6-r2c4 Δ UL2, cos6-r2c5 Δ UL2, cos6-r2c6 Δ UL2 (be commonly referred to as cos6-rXcY Δ UL2, collection of illustrative plates is seen accompanying drawing 6) respectively.With cos6-r2c1 Δ UL2, cos6-r2c3 Δ UL2, cos6-r2c4 Δ UL2, cos6-r2c5 Δ UL2, one of among the cos6-r2c6 Δ UL2 respectively with cos14, cos28, cos48, mole such as cos56 mixes, cut the cos skeleton with the PacI enzyme, with liposome cotransfection BHK-21 cell, homologous recombination takes place and produces HSV-r2c1 respectively in 5 HSV1 fragments in cell, HSV-r2c3, HSV-r2c4, HSV-r2c5, recombinant viruses such as HSV-r2c6: cell begins to occur pathology after 5 days, treat to receive the nutrient solution supernatant after the complete pathology of cell, the centrifugal 5min of 2000r/min, the supernatant packing is stored in-20 ℃.The probability of the reorganization HSV1 virus that contains target DNA fragment that produces with this method reaches 50～100%.Be easy to obtain single recombinant virus by plaque select.

Equally, the XbaI site with gene fragments such as r2c1, r2c3, r2c4 and r2c5 are inserted cos56 respectively also can obtain and the identical recombinant viruses of recombinant virus function such as above-mentioned HSV-r2c1, HSV-r2c3, HSV-r2c4, HSV-r2c5, HSV-r2c6.Its preparation process is: will insert respectively in the XbaI site of cos56 through r2c1, r2c3, r2c4, r2c5 and the r2c6 gene fragment of XbaI enzyme cutting, be built into reorganization clay cos56-r2c1 Δ UL2, cos56-r2c3 Δ UL2, cos56-r2c4 Δ UL2, cos56-r2c5 Δ UL2, cos56-r2c6 Δ UL2 (be commonly referred to as cos56-rXcY Δ UL2, collection of illustrative plates is seen accompanying drawing 7) respectively.With cos56-r2c1 Δ UL2, cos56-r2c3 Δ UL2, cos56-r2c4 Δ UL2, cos56-r2c5 Δ UL2, one of among the cos56-r2c6 Δ UL2 respectively with cos6, cos14, cos28, mole such as cos48 mixes, cut the cos skeleton with the PacI enzyme, with liposome cotransfection BHK-21 cell, homologous recombination takes place and produces HSV-r2c1 respectively in 5 HSV1 fragments in cell, HSV-r2c3, HSV-r2c4, HSV-r2c5, recombinant viruses such as HSV-r2c6: cell begins to occur pathology after 5 days, treat to receive the nutrient solution supernatant after the complete pathology of cell, the centrifugal 5min of 2000r/min, the supernatant packing is stored in-20 ℃.The probability of the reorganization HSV1 virus that contains target DNA fragment that produces with this method can reach 50～100% equally.Be easy to obtain single recombinant virus by plaque select.

In addition, with gene fragments such as r2c1, r2c3, r2c4, r2c5 and r2c6 by homology arm reorganization, transposon, fixed point insert, mode such as insertion is inserted in the HSV1 genome at random, can obtain equally and the identical recombinant viruses of recombinant virus function such as above-mentioned HSV-r2c1, HSV-r2c3, HSV-r2c4, HSV-r2c5, HSV-r2c6.

Equally, recombinant viruses such as the HSV-r2c1, the HSV-r2c3 that describe of the present invention, HSV-r2c4, HSV-r2c5, HSV-r2c6 also can be other dna sequence dnas of dna fragmentation homologous that has inserted with SEQ ID NO.1, SEQ ID NO.2, SEQ ID NO.3, SEQ ID NO.4 or SEQID NO.5." other homologous DNA sequence " refers to non-SEQ ID NO.1, SEQ ID NO.2, SEQ ID NO.3, SEQ ID NO.4 or SEQ ID NO.5, but with it certain dna sequence dna homology arranged, and can play other dna sequence dna of AAV carrier helper viral function equally.

Prepare respectively with 5 strain recombinant herpes simplex virus have AAV1,3,4,5, the rAAV1,3,4,5,6 of 6 serotype:

Prepare respectively with 5 strain recombinant herpes simplex virus have AAV1,3,4,5 respectively, 5 kinds of reorganization AAV of 6 serotype capsid protein, specifically comprise: rAAV1, rAAV3, rAAV4, rAAV5, rAAV6.

In AAV1,3,4,5,6, the rep difference maximum of the rep of AAV5 and AAV2, therefore needs could effectively guarantee the gene replication of AAV5 and the packing of rAAV5 virus with the part that the rep of part A AV5 replaces the rep of AAV2.According to bibliographical information, it is necessary that preceding 232 amino acid (about 700bp) of the rep of AAV2 are that Rep albumen is correctly discerned the ITR of AAV2.(Yoon，M，D.Smith，P.Ward，F，et?el.2001.J.Virol.75：3230-3239)。HSV-r2c5 of the present invention has left and taken the about 860bp of rep gene 5 ' end (BamHI site) of AAV2, infects the AAV packaging cell line that contains ITR (AAV2)-foreign gene-ITR (AAV2) with it, has obtained having the rAAV5 virus of AAV5 serotype.

Except that AAV5, AAV1,3,4,6 rep and AAV2 have bigger homology, therefore, HSV-r2c1, the HSV-r2c3 that the present invention makes up, the rep gene of the AAV in the recombinant viruses such as HSV-r2c4, HSV-r2c6 are basically all from AAV2, infect the AAV packaging cell line that contains ITR (AAV2)-foreign gene-ITR (AAV2) respectively with the former, can be had the rAAV1,3,4,6 of AAV1,3,4,6 serotype respectively.

The building process of AAV packaging cell line is: make up the plasmid that contains " ITR (AAV2)-foreign gene-ITR (AAV2) " and resistant gene such as neor, transfection is to the passage cell strain of HSV1 sensitivity, in BHK-21, with the strain of G418 screening resistant cell, promptly obtain the AAV packaging cell line, helper virus with the rHSV1 of the rep-cap that contains AAV infects this cell strain, promptly obtains the rAAV virus vector.(method reference: Wu Xiaobing etc. are fundamental construction recombinant herpes simplex virus and uses thereof with the clay, Chinese patent application numbers 98101753.3; Wu Xiaobing etc. are used for generation of the global function helper virus that recombinant adeno-associated virus produces and uses thereof, Chinese patent application numbers 98120033.8).

Embodiment:

Following examples have been done detailed description to preparation and the purposes of the global function helper virus of the different serotypes that is used for recombinant adeno-associated virus production of the present invention, but and do not mean that restriction content of the present invention.

The structure of embodiment 1 cos6-r2c1 Δ UL2

With AAV1 is template, and PCR method amplifies corresponding cap1 (AAV1) (primer is seen primer sequence 1,2).Reaction conditions: 94 ℃ of 30sec, 55 ℃ of 30sec, 72 ℃ of 3min, 30 circulations, obtain the PCR fragment cap1 of 2210bp, behind restriction enzyme KpnI+XbaI double digestion, be connected with the rep2 (1721bp) of the AAV2 that cuts out with KpnI+XbaI from pSSV9, to connect product and pack in the XbaI site of pGEM-p3zf (+) plasmid (Promega company), obtain the p3zf-r2c1 plasmid.From the p3zf-r2c1 plasmid, downcut r2c1 (about 4347bp) with XbaI again, in the XbaI site of the cos6 that packs into, obtain cos6-r2c1 Δ UL2.

The structure of embodiment 2 cos6-r2c3 Δ UL2

With AAV3 is template, and PCR method amplifies corresponding cap3 (AAV3) (primer is seen primer sequence 3,4).Reaction conditions: 94 ℃ of 30sec, 55 ℃ of 30sec, 72 ℃ of 3min, 30 circulations, obtain the PCR fragment cap3 of 2040bp, behind restriction enzyme XhoI+XbaI double digestion, be connected with the rep2 (2040bp) of the AAV2 that cuts out with XhoI+XbaI from pSSV9, to connect product and pack in the XbaI site of pGEM-p3zf (+) plasmid (Promega company), obtain the p3zf-r2c3 plasmid.From the p3zf-r2c3 plasmid, downcut r2c3 (about 4287bp) with XbaI again, in the XbaI site of the cos6 that packs into, obtain cos6-r2c3 Δ UL2.

The structure of embodiment 3 cos6-r2c4 Δ UL2

With AAV1 is template, and PCR method amplifies corresponding cap4 (AAV4) (primer is seen primer sequence 5,6).Reaction conditions: 94 ℃ of 30sec, 55 ℃ of 30sec, 72 ℃ of 3min, 30 circulations obtain the PCR fragment cap4 of 2255bp, after cutting with restriction enzyme KpnI enzyme, with cut out with KpnI from pSSV9, remove the big fragment contain the cap2 dna fragmentation and link to each other, obtain the SSV9-cap4 plasmid.From the SSV9-cap4 plasmid, downcut r2c4 (about 4536bp) with XbaI again, in the XbaI site of the cos6 that packs into, obtain cos6-r2c4 Δ UL2.

The structure of embodiment 4 cos6-r2c5 Δ UL2

With AAV5 is template, and PCR method amplifies corresponding cap5 (AAV5) (primer is seen primer sequence 7,8).Reaction conditions: 94 ℃ of 30sec, 55 ℃ of 30sec, 72 ℃ of 3min, 30 circulations, obtain the PCR fragment cap5 of 2170bp, behind restriction enzyme BamHI+XbaI double digestion, be connected with the rep2 (860bp) of the AAV2 that cuts out with BamHI+XbaI from pSSV9, to connect product and pack in the XbaI site of pGEM-p3zf (+) plasmid (Promega company), obtain the p3zf-r2c5 plasmid.From the p3zf-r2c5 plasmid, downcut r2c5 (about 4314bp) with XbaI again, in the XbaI site of the cos6 that packs into, obtain cos6-r2c5 Δ UL2.

The structure of embodiment 5 cos6-r2c6 Δ UL2

With AAV1 is template, and PCR method amplifies corresponding cap6 (AAV6) (primer is seen primer sequence 9,10).Reaction conditions: 94 ℃ of 30sec, 55 ℃ of 30sec, 72 ℃ of 3min, 30 circulations, obtain the PCR fragment cap6 of 2210bp, behind restriction enzyme KpnI+XbaI double digestion, be connected with the rep2 (1721bp) of the AAV2 that cuts out with KpnI+XbaI from pSSV9, to connect product and pack among the pGEM-p3zf (+) (Promega company), obtain the p3zf-r2c6 plasmid.From the p3zf-r2c6 plasmid, downcut r2c6 (about 4239bp) with XbaI again, in the XbaI site of the cos6 that packs into, obtain cos6-r2c6 Δ UL2.

Primer sequence: primer sequence 1:AAV1 cap upstream primer: 5 '-GTCTGGAGCATGACTTTGGC-3, primer sequence 2:AAV1 cap downstream primer: 5 '-TCTAGAAGCGCAACCAAGCAGTTAAT-3, primer sequence 3:AAV3 cap upstream primer: 5 '-TCTAGAGGTCAAAGAGACTGTGGGGA-3, primer sequence 4:AAV3 cap downstream primer: 5 '-TCTAGATGCACAAGAGCCAAAGTTCA-3, primer sequence 5:AAV4 cap upstream primer: 5 '-GCGGACAGGTACCAAAACAA-3, primer sequence 6:AAV4 cap downstream primer: 5 '-GAAGGATTCGCAGGTACCGG-3, primer sequence 7:AAV5 cap upstream primer: 5 '-GGATCCAGGAAAATCAGGAG-3, primer sequence 8:AAV5 cap downstream primer: 5 '-TCTAGACATGAATGGGTTAAAGGG-3, primer sequence 9:AAV6 cap upstream primer: 5 '-TTTGCCGACAGGTACCAAAA-3, primer sequence 10:AAV6 cap downstream primer: 5 '-TCTAGACACACAATTACAGGGGAC-3

The preparation of embodiment 6 reorganization HSV-r2c1

With cos6-r2c1 Δ UL2 and cos14, cos28, cos48, mole such as 5 clays such as cos56 mixes, and cuts cos skeleton (needn't separate removal) with the Pacl enzyme, with phenol, phenol/chloroform (1: 1) and each extracting of chloroform once, draw supernatant, with 2.5 times of dehydrated alcohol deposit D NA.With BHK-21 cell (about 2 * 106) cell that lipofactamine (GIBCO BRL) 20ul and 10ug DNA are paved with by product description cotransfection 80%, homologous recombination will take place and produce the HSV-r2c1 recombinant virus respectively in 5 HSV1 fragments in cell.Use the 37 ℃ of cultivations of RPMI-1640 that contain 2%FBS behind the transfection 24h instead, change liquid every day once.Cell begins to occur pathology after 5 days, treat to receive the nutrient solution supernatant after the complete pathology of cell, and the centrifugal 5min of 2000r/min, the supernatant packing is stored in-20 ℃.The recombinant virus that obtains is carried out the plaque purifying twice, can obtain single HSV-r2c1 recombinant virus.

The preparation of embodiment 7 reorganization HSV-r2c3

With cos6-r2c3 Δ UL2 and cos14, cos28, cos48, mole such as 5 clays such as cos56 mixes, and cuts cos skeleton (needn't separate removal) with the PacI enzyme, with phenol, phenol/chloroform (1: 1) and each extracting of chloroform once, draw supernatant, with 2.5 times of dehydrated alcohol deposit D NA.With BHK-21 cell (about 2 * 106) cell that lipofactamine (GIBCO BRL) 20ul and 10ug DNA are paved with by product description cotransfection 80%, homologous recombination will take place and produce the HSV-r2c3 recombinant virus respectively in 5 HSV1 fragments in cell.Use the 37 ℃ of cultivations of RPMI-1640 that contain 2%FBS behind the transfection 24h instead, change liquid every day once.Cell begins to occur pathology after 5 days, treat to receive the nutrient solution supernatant after the complete pathology of cell, and the centrifugal 5min of 2000r/min, the supernatant packing is stored in-20 ℃.The recombinant virus that obtains is carried out the plaque purifying twice, can obtain single HSV-r2c3 recombinant virus.

The preparation of embodiment 8 reorganization HSV-r2c4

With cos6-r2c4 Δ UL2 and cos14, cos28, cos48, mole such as 5 clays such as cos56 mixes, and cuts cos skeleton (needn't separate removal) with the PacI enzyme, with phenol, phenol/chloroform (1: 1) and each extracting of chloroform once, draw supernatant, with 2.5 times of dehydrated alcohol deposit D NA.With BHK-21 cell (about 2 * 106) cell that lipofactamine (GIBCO BRL) 20ul and 10ug DNA are paved with by product description cotransfection 80%, homologous recombination will take place and produce the HSV-r2c4 recombinant virus respectively in 5 HSV1 fragments in cell.Use the 37 ℃ of cultivations of RPMI-1640 that contain 2%FBS behind the transfection 24h instead, change liquid every day once.Cell begins to occur pathology after 5 days, treat to receive the nutrient solution supernatant after the complete pathology of cell, and the centrifugal 5min of 2000r/min, the supernatant packing is stored in-20 ℃.The recombinant virus that obtains is carried out the plaque purifying twice, can obtain single HSV-r2c4 recombinant virus.

The preparation of embodiment 9 reorganization HSV-r2c5

With cos6-r2c5 Δ UL2 and cos14, cos28, cos48, mole such as 5 clays such as cos56 mixes, and cuts cos skeleton (needn't separate removal) with the PacI enzyme, with phenol, phenol/chloroform (1: 1) and each extracting of chloroform once, draw supernatant, with 2.5 times of dehydrated alcohol deposit D NA.With BHK-21 cell (about 2 * 106) cell that lipofactamine (GIBCO BRL) 20ul and 10ug DNA are paved with by product description cotransfection 80%, homologous recombination will take place and produce the HSV-r2c5 recombinant virus respectively in 5 HSV1 fragments in cell.Use the 37 ℃ of cultivations of RPMI-1640 that contain 2%FBs behind the transfection 24h instead, change liquid every day once.Cell begins to occur pathology after 5 days, treat to receive the nutrient solution supernatant after the complete pathology of cell, and the centrifugal 5min of 2000r/min, the supernatant packing is stored in-20 ℃.The recombinant virus that obtains is carried out the plaque purifying twice, can obtain single HSV-r2c5 recombinant virus.

The preparation of embodiment 10 reorganization HSV-r2c6

With cos6-r2c6 Δ UL2 and cos14, cos28, cos48, mole such as 5 clays such as cos56 mixes, and cuts cos skeleton (needn't separate removal) with the PacI enzyme, with phenol, phenol/chloroform (1: 1) and each extracting of chloroform once, draw supernatant, with 2.5 times of dehydrated alcohol deposit D NA.With BHK-21 cell (about 2 * 106) cell that lipofactamine (GIBCO BRL) 20ul and 10ug DNA are paved with by product description cotransfection 80%, homologous recombination will take place and produce the HSV-r2c6 recombinant virus respectively in 5 HSV1 fragments in cell.Use the 37 ℃ of cultivations of RPMI-1640 that contain 2%FBS behind the transfection 24h instead, change liquid every day once.Cell begins to occur pathology after 5 days, treat to receive the nutrient solution supernatant after the complete pathology of cell, and the centrifugal 5min of 2000r/min, the supernatant packing is stored in-20 ℃.The recombinant virus that obtains is carried out the plaque purifying twice, can obtain single HSV-r2c6 recombinant virus.

The foundation of embodiment 11 AAV packaging cell line BHK/pSNAV-GFP

At pSNAV-1 plasmid (Wu Zhijian, Wu Xiaobing, Hou Yunde, the research of the structure of series adenopathy adjoint virus carrier and expression tilactase, the virus journal, 2000,16 (1), be built into the recombinant plasmid pSNAV-GFP that contains the GFP gene on basis 1-6), its structure is for having the plasmid (seeing accompanying drawing 8) of " ITR (AAV2)-foreign gene-ITR (AAV2) " and resistant gene neor.This plasmid is imported BHK-21 cell (ATCC CCL-10) with liposome method, select to cultivate 10-15d, the resistant cell strain called after BHK/pSNAV-GFP of acquisition with G418 200ug/ml.

Embodiment 12 has the preparation of the rAAV/r2c1-GFP of AAV1 serotype

Infect the BHK/pSNAV-GFP cell with HSV-r2c1,4 cracking cells of cytopathy (36-72h) back multigelation.Contain rAAV/r2c1-GFP and helper virus HSV-r2c1 in the cell pyrolysis liquid.Low-speed centrifugal is removed cell debris, gets 56 ℃ of lysates and handles 30min with deactivation helper virus HSV-r2c1, the rAAV/r2c1-GFP that obtains having AAV1 serotype.Be used for external, the interior mammalian cell of cultivating that infects of body.

Embodiment 13 has the preparation of the rAAV/r2c3-GFP of AAV3 serotype

Infect the BHK/pSNAV-GFP cell with HSV-r2c3,4 cracking cells of cytopathy (36-72h) back multigelation.Contain rAAV/r2c3-GFP and helper virus HSV-r2c3 in the cell pyrolysis liquid.Low-speed centrifugal is removed cell debris, gets 56 ℃ of lysates and handles 30min with deactivation helper virus HSV-r2c3, the rAAV/r2c3-GFP that obtains having AAV3 serotype.Be used for external, the interior mammalian cell of cultivating that infects of body.

Embodiment 14 has the preparation of the rAAV/r2c4-GFP of AAV4 serotype

Infect the BHK/pSNAV-GFP cell with HSV-r2c4,4 cracking cells of cytopathy (36-72h) back multigelation.Contain rAAV/r2c4-GFP and helper virus HSV-r2c4 in the cell pyrolysis liquid.Low-speed centrifugal is removed cell debris, gets 56 ℃ of lysates and handles 30min with deactivation helper virus HSV-r2c4, the rAAV/r2c4-GFP that obtains having AAV4 serotype.Be used for external, the interior mammalian cell of cultivating that infects of body.

Embodiment 15 has the preparation of the rAAV/r2c5-GFP of AAV5 serotype

Infect the BHK/pSNAV-GFP cell with HSV-r2c5,4 cracking cells of cytopathy (36-72h) back multigelation.Contain rAAV/r2c5-GFP and helper virus HSV-r2c5 in the cell pyrolysis liquid.Low-speed centrifugal is removed cell debris, gets 56 ℃ of lysates and handles 30min with deactivation helper virus HSV-r2c5, the rAAV/r2c5-GFP that obtains having AAV5 serotype.Be used for external, the interior mammalian cell of cultivating that infects of body.

Embodiment 16 has the preparation of the rAAV/r2c6-GFP of AAV6 serotype

Infect the BHK/pSNAV-GFP cell with HSV-r2c6,4 cracking cells of cytopathy (36-72h) back multigelation.Contain rAAV/r2c6-GFP and helper virus HSV-r2c6 in the cell pyrolysis liquid.Low-speed centrifugal is removed cell debris, gets 56 ℃ of lysates and handles 30min with deactivation helper virus HSV-r2c6, the rAAV/r2c6-GFP that obtains having AAV6 serotype.Be used for external, the interior mammalian cell of cultivating that infects of body.

The embodiment 17 usefulness rAAV/r2c1-GFP cultured cell in vitro of transduceing

Get rAAV/r2c1-GFP virus (MOI=1) and add in the BHK-21 cell of cultivating (80% is paved with), (excitation wavelength 490nm) observation under fluorescent microscope all can be seen a large amount of green cells behind the 24-48h.The rAAV/r2c1-GFP virus that shows generation has infectivity, and can will express in the foreign gene transfered cell.

The embodiment 18 usefulness rAAV/r2c3-GFP cultured cell in vitro of transduceing

Get rAAV/r2c3-GFP virus (MOI=1) and add in the BHK-21 cell of cultivating (80% is paved with), (excitation wavelength 490nm) observation under fluorescent microscope all can be seen a large amount of green cells behind the 24-48h.The rAAV/r2c3-GFP virus that shows generation has infectivity, and can will express in the foreign gene transfered cell.

The embodiment 19 usefulness rAAV/r2c4-GFP cultured cell in vitro of transduceing

Get rAAV/r2c4-GFP virus (MOI=1) and add in the BHK-21 cell of cultivating (80% is paved with), (excitation wavelength 490nm) observation under fluorescent microscope all can be seen a large amount of green cells behind the 24-48h.The rAAV/r2c4-GFP virus that shows generation has infectivity, and can will express in the foreign gene transfered cell.

The embodiment 20 usefulness rAAV/r2c5-GFP cultured cell in vitro of transduceing

Get rAAV/r2c5-GFP virus (MOI=1) and add in the BHK-21 cell of cultivating (80% is paved with), (excitation wavelength 490nm) observation under fluorescent microscope all can be seen a large amount of green cells behind the 24-48h.The rAAV/r2c5-GFP virus that shows generation has infectivity, and can will express in the foreign gene transfered cell.

The embodiment 21 usefulness rAAV/r2c6-GFP cultured cell in vitro of transduceing

Get rAAV/r2c6-GFP virus (MOI=1) and add in the BHK-21 cell of cultivating (80% is paved with), (excitation wavelength 490nm) observation under fluorescent microscope all can be seen a large amount of green cells behind the 24-48h.The rAAV/r2c6-GFP virus that shows generation has infectivity, and can will express in the foreign gene transfered cell.

The dna sequence dna of each rXcY: comprise r2c1, r2c3, r2c4, r2c5, r2c6 etc.

SEQ ID NO.1: [Electronic version File name: r2c1 (Seq1). WorkFile] Sequence Name: seq1: rep (AAV2)-cap (AAV1) <400> PreSequenceString: ctagagtcct gtattagagg tcacgtgagt gttttgcgac attttgcgac accatgtggt 60cacgctgggt atttaagccc gagtgagcac gcagggtctc cattttgaag cgggaggttt 120gaacgcgcag ccgccatgcc ggggttttac gagattgtga ttaaggtccc cagcgacctt 180gacgggcatc tgcccggcat ttctgacagc tttgtgaact gggtggccga gaaggaatgg 240gagttgccgc cagattctga catggatctg aatctgattg agcaggcacc cctgaccgtg 300gccgagaagc tgcagcgcga ctttctgacg gaatggcgcc gtgtgagtaa ggccccggag 360gcccttttct ttgtgcaatt tgagaaggga gagagctact tccacatgca cgtgctcgtg 420gaaaccaccg gggtgaaatc catggttttg ggacgtttcc tgagtcagat tcgcgaaaaa 480ctgattcaga gaatttaccg cgggatcgag ccgactttgc caaactggtt cgcggtcaca 540aagaccagaa atggcgccgg aggcgggaac aaggtggtgg atgagtgcta catccccaat 600tacttgctcc ccaaaaccca gcctgagctc cagtgggcgt ggactaatat ggaacagtat 660ttaagcgcct gtttgaatct cacggagcgt aaacggttgg tggcgcagca tctgacgcac 720gtgtcgcaga cgcaggagca gaacaaagag aatcagaatc ccaattctga tgcgccggtg 780atcagatcaa aaacttcagc caggtacatg gagctggtcg ggtggctcgt ggacaagggg 840attacctcgg agaagcagtg gatccaggag gaccaggcct catacatctc cttcaatgcg 900gcctccaact cgcggtccca aatcaaggct gccttggaca atgcgggaaa gattatgagc 960ctgactaaaa ccgcccccga ctacctggtg ggccagcagc ccgtggagga catttccagc 1020aatcggattt ataaaatttt ggaactaaac gggtacgatc cccaatatgc ggcttccgtc 1080tttctgggat gggccacgaa aaagttcggc aagaggaaca ccatctggct gtttgggcct 1140gcaactaccg ggaagaccaa catcgcggag gccatagccc acactgtgcc cttctacggg 1200tgcgtaaact ggaccaatga gaactttccc ttcaacgact gtgtcgacaa gatggtgatc 1260tggtgggagg aggggaagat gaccgccaag gtcgtggagt cggccaaagc cattctggga 1320ggaagcaagg tgcgcgtgga ccagaaatgc aagtcctcgg cccagataga cccgactccc 1380gtgatcgtca cctccaacac caacatgtgc gccgtgattg acgggaactc aacgaccttc 1440gaacaccagc agccgttgca agaccggatg ttcaaatttg aactcacccg ccgtctggat 1500catgactttg ggaaggtcac caagcaggaa gtcaaagact ttttccggtg ggcaaaggat 1560cacgtggttg aggtggagca tgaattctac gtcaaaaagg gtggagccaa gaaaagaccc 1620gcccccagtg acgcagatat aagtgagccc aaacgggtgc gcgagtcagt tgcgcagcca 1680tcgacgtcag acgcggaagc ttcgatcaac tacgcagaca ggtaccaaaa caaatgttct 1740cgtcacgcgg gcatgcttca gatgctgttt ccctgcaaga catgcgagag aatgaatcag 1800aatttcaaca tttgcttcac gcacgggacg agagactgtt cagagtgctt ccccggcgtg 1860tcagaatctc aaccggtcgt cagaaagagg acgtatcgga aactctgtgc cattcatcat 1920ctgctggggc gggctcccga gattgcttgc tcggcctgcg atctggtcaa cgtggacctg 1980gatgactgtg tttctgagca ataaatgact taaaccaggt atggctgccg atggttatct 2040tccagattgg ctcgaggaca acctctctga gggcattcgc gagtggtggg acttgaaacc 2100tggagccccg aagcccaaag ccaaccagca aaagcaggac gacggccggg gtctggtgct 2160tcctggctac aagtacctcg gacccttcaa cggactcgac aagggggagc ccgtcaacgc 2220ggcggacgca gcggccctcg agcacgacaa ggcctacgac cagcagctca aagcgggtga 2280caatccgtac ctgcggtata accacgccga cgccgagttt caggagcgtctgcaagaaga 2340tacgtctttt gggggcaacc tcgggcgagc agtcttccag gccaagaagc gggttctcga 2400acctctcggt ctggttgagg aaggcgctaa gacggctcct ggaaagaaac gtccggtaga 2460gcagtcgcca caagagccag actcctcctc gggcatcggc aagacaggcc agcagcccgc 2520taaaaagaga ctcaattttg gtcagactgg cgactcagag tcagtccccg atccacaacc 2580tctcggagaa cctccagcaa cccccgctgc tgtgggacct actacaatgg cttcaggcgg 2640tggcgcacca atggcagaca ataacgaagg cgccgacgga gtgggtaatg cctcaggaaa 2700ttggcattgc gattccacat ggctgggcga cagagtcatc accaccagca cccgcacctg 2760ggccttgccc acctacaata accacctcta caagcaaatc tccagtgctt caacgggggc 2820cagcaacgac aaccactact tcggctacag caccccctgg gggtattttg atttcaacag 2880attccactgc cacttttcac cacgtgactg gcagcgactc atcaacaaca attggggatt 2940ccggcccaag agactcaact tcaaactctt caacatccaa gtcaaggagg tcacgacgaa 3000tgatggcgtc acaaccatcg ctaataacct taccagcacg gttcaagtct tctcggactc 3060ggagtaccag cttccgtacg tcctcggctc tgcgcaccag ggctgcctcc ctccgttccc 3120ggcggacgtg ttcatgattc cgcaatacgg ctacctgacg ctcaacaatg gcagccaagc 3180cgtgggacgt tcatcctttt actgcctgga atatttccct tctcagatgc tgagaacggg 3240caacaacttt accttcagct acacctttga ggaagtgcct ttccacagca gctacgcgca 3300cagccagagc ctggaccggc tgatgaatcc tctcatcgac caatacctgt attacctgaa 3360cagaactcaa aatcagtccg gaagtgccca aaacaaggac ttgctgttta gccgtgggtc 3420tccagctggc atgtctgtgc agcccaaaaa ctggctacct ggaccctgtt atcggcagca 3480gcgcgtttct aaaacaaaaa cagacaacaa caacagcaat tttacctgga ctggtgcttc 3540aaaatataac ctcaatgggc gtgaatccat catcaaccct ggcactgcta tggcctcaca 3600caaagacgac gaagacaagt tctttcccat gagcggtgtc atgatttttg gaaaagagag 3660cgccggagct tcaaacactg cattggacaa tgtcatgatt acagacgaag aggaaattaa 3720agccactaac cctgtggcca ccgaaagatt tgggaccgtg gcagtcaatt tccagagcag 3780cagcacagac cctgcgaccg gagatgtgca tgctatggga gcattacctg gcatggtgtg 3840gcaagataga gacgtgtacc tgcagggtcc catttgggcc aaaattcctc acacagatgg 3900acactttcac ccgtctcctc ttatgggcgg ctttggactc aagaacccgc ctcctcagat 3960cctcatcaaa aacacgcctg ttcctgcgaa tcctccggcg gagttttcag ctacaaagtt 4020tgcttcattc atcacccaat actccacagg acaagtgagt gtggaaattg aatgggagct 4080gcagaaagaa aacagcaagc gctggaatcc cgaagtgcag tacacatcca attatgcaaa 4140atctgccaac gttgatttta ctgtggacaa caatggactt tatactgagc ctcgccccat 4200tggcacccgt taccttaccc gtcccctgta attacgtgtt aatcaataaa ccggttgatt 4260cgtttcagtt gaactttggt ctcctgtcct tcttatctta tcggttacca tggttatagc 4320ttacacatta actgcttggt tgcgctt 4347 <212> Type: DNA <211> Length: 4347...

SequenceName：seq1：rep(AAV2)-cap(AAV1)

SequenceDescription: Custom Codon ------------ Sequence Name: seq1: rep (AAV2)-cap (AAV1) SEQ ID NO.2: [Electronic version File name: r2c3 (Seq2). WorkFile] Sequence Name: seq2: rep (AAV2)-cap (AAV3) <400> PreSequenceString: ctagagtcct gtattagagg tcacgtgagt gttttgcgac attttgcgac accatgtggt 60cacgctgggt atttaagccc gagtgagcac gcagggtctc cattttgaag cgggaggttt 120gaacgcgcag ccgccatgcc ggggttttac gagattgtga ttaaggtccc cagcgacctt 180gacgggcatc tgcccggcat ttctgacagc tttgtgaact gggtggccga gaaggaatgg 240gagttgccgc cagattctga catggatctg aatctgattg agcaggcacc cctgaccgtg 300gccgagaagc tgcagcgcga ctttctgacg gaatggcgcc gtgtgagtaa ggccccggag 360gcccttttct ttgtgcaatt tgagaaggga gagagctact tccacatgca cgtgctcgtg 420gaaaccaccg gggtgaaatc catggttttg ggacgtttcc tgagtcagat tcgcgaaaaa 480ctgattcaga gaatttaccg cgggatcgag ccgactttgc caaactggtt cgcggtcaca 540aagaccagaa atggcgccgg aggcgggaac aaggtggtgg atgagtgcta catccccaat 600tacttgctcc ccaaaaccca gcctgagctc cagtgggcgt ggactaatat ggaacagtat 660ttaagcgcct gtttgaatct cacggagcgt aaacggttgg tggcgcagca tctgacgcac 720gtgtcgcaga cgcaggagca gaacaaagag aatcagaatc ccaattctga tgcgccggtg 780atcagatcaa aaacttcagc caggtacatg gagctggtcg ggtggctcgt ggacaagggg 840attacctcgg agaagcagtg gatccaggag gaccaggcct catacatctc cttcaatgcg 900gcctccaact cgcggtccca aatcaaggct gccttggaca atgcgggaaa gattatgagc 960ctgactaaaa ccgcccccga ctacctggtg ggccagcagc ccgtggagga catttccagc 1020aatcggattt ataaaatttt ggaactaaac gggtacgatc cccaatatgc ggcttccgtc 1080tttctgggat gggccacgaa aaagttcggc aagaggaaca ccatctggct gtttgggcct 1140gcaactaccg ggaagaccaa catcgcggag gccatagccc acactgtgcc cttctacggg 1200tgcgtaaact ggaccaatga gaactttccc ttcaacgact gtgtcgacaa gatggtgatc 1260tggtgggagg aggggaagat gaccgccaag gtcgtggagt cggccaaagc cattctggga 1320ggaagcaagg tgcgcgtgga ccagaaatgc aagtcctcgg cccagataga cccgactccc 1380gtgatcgtca cctccaacac caacatgtgc gccgtgattg acgggaactc aacgaccttc 1440gaacaccagc agccgttgca agaccggatg ttcaaatttg aactcacccg ccgtctggat 1500catgactttg ggaaggtcac caagcaggaa gtcaaagact ttttccggtg ggcaaaggat 1560cacgtggttg aggtggagca tgaattctac gtcaaaaagg gtggagccaa gaaaagaccc 1620gcccccagtg acgcagatat aagtgagccc aaacgggtgc gcgagtcagt tgcgcagcca 1680tcgacgtcag acgcggaagc ttcgatcaac tacgcagaca ggtaccaaaa caaatgttct 1740cgtcacgtgg gcatgaatct gatgctgttt ccctgcagac aatgcgagag aatgaatcag 1800aattcaaata tctgcttcac tcacggacag aaagactgtt tagagtgctt tcccgtgtca 1860gaatctcaac ccgtttctgt cgtcaaaaag gcgtatcaga aactgtgcta cattcatcat 1920atcatgggaa aggtgccaga cgcttgcact gcctgcgatc tggtcaatgt ggatttggat 1980gactgcatct ttgaacaata aatgatttaa atcaggtatg gctgccgatg gttatcttcc 2040agattggctc gaggacaacc tttctgaagg cattcgtgag tggtgggctc tgaaacctgg 2100agtccctcaa cccaaagcga accaacaaca ccaggacaac cgtcggggtc ttgtgcttcc 2160gggttacaaa tacctcggac ccggtaacgg actcgacaaa ggagagccgg tcaacgaggc 2220ggacgcggca gccctcgaac acgacaaagc ttacgaccag cagctcaagg ccggtgacaa 2280cccgtacctc aagtacaacc acgccgacgc cgagtttcag gagcgtcttc aagaagatac 2340gtcttttggg ggcaaccttg gcagagcagt cttccaggcc aaaaagagga tccttgagcc 2400tcttggtctg gttgaggaag cagctaaaac ggctcctgga aagaaggggg ctgtagatca 2460gtctcctcag gaaccggact catcatctgg tgttggcaaa tcgggcaaac agcctgccag 2520aaaaagacta aatttcggtc agactggaga ctcagagtca gtcccagacc ctcaacctct 2580cggagaacca ccagcagccc ccacaagttt gggatctaat acaatggctt caggcggtgg 2640cgcaccaatg gcagacaata acgagggtgc cgatggagtg ggtaattcct caggaaattg 2700gcattgcgat tcccaatggc tgggcgacag agtcatcacc accagcacca gaacctgggc 2760cctgcccact tacaacaacc atctctacaa gcaaatctcc agccaatcag gagcttcaaa 2820cgacaaccac tactttggct acagcacccc ttgggggtat tttgacttta acagattcca 2880ctgccacttc tcaccacgtg actggcagcg actcattaac aacaactggg gattccggcc 2940caagaaactc agcttcaagc tcttcaacat ccaagttaga ggggtcacgc agaacgatgg 3000cacgacgact attgccaata accttaccag cacggttcaa gtgtttacgg actcggagta 3060tcagctcccg tacgtgctcg ggtcggcgca ccaaggctgt ctcccgccgt ttccagcgga 3120cgtcttcatg gtccctcagt atggatacct caccctgaac aacggaagtc aagcggtggg 3180acgctcatcc ttttactgcc tggagtactt cccttcgcag atgctaagga ctggaaataa 3240cttccaattc agctatacct tcgaggatgt accttttcac agcagctacg ctcacagcca 3300gagtttggat cgcttgatga atcctcttat tgatcagtat ctgtactacc tgaacagaac 3360gcaaggaaca acctctggaa caaccaacca atcacggctg ctttttagcc aggctgggcc 3420tcagtctatg tctttgcagg ccagaaattg gctacctggg ccctgctacc ggcaacagag 3480actttcaaag actgctaacg acaacaacaa cagtaacttt ccttggacag cggccagcaa 3540atatcatctc aatggccgcg actcgctggt gaatccagga ccagctatgg ccagtcacaa 3600ggacgatgaa gaaaaatttt tccctatgca cggcaatcta atatttggca aagaagggac 3660aacggcaagt aacgcagaat tagataatgt aatgattacg gatgaagaag agattcgtac 3720caccaatcct gtggcaacag agcagtatgg aactgtggca aataacttgc agagctcaaa 3780tacagctccc acgactggaa ctgtcaatca tcagggggcc ttacctggca tggtgtggca 3840agatcgtgac gtgtaccttc aaggacctat ctgggcaaag attcctcaca cggatggaca 3900ctttcatcct tctcctctga tgggaggctt tggactgaaa catccgcctc ctcaaatcat 3960gatcaaaaat actccggtac cggcaaatcc tccgacgact ttcagcccgg ccaagtttgc 4020ttcatttatc actcagtact ccactggaca ggtcagcgtg gaaattgagt gggagctaca 4080gaaagaaaac agcaaacgtt ggaatccaga gattcagtac acttccaact acaacaagtc 4140tgttaatgtg gactttactg tagacactaa tggtgtttat agtgaacctc gccctattgg 4200aacccggtat ctcacacgaa acttgtgaat cctggttaat caataaaccg tttaattcgt 4260ttcagttgaa ctttggctct tgtgcat 4287 <212 > Type: DNA <211> Length: 4287...

SequenceName: seq2: rep (AAV2)-cap (AAV3) SEQ ID NO.3: [Electronic version File name: r2c4 (Seq3). WorkFile] Sequence Name: seq1: rep (AAV2)-cap (AAV1) <400> PreSequenceSrting : ctagagtcct gtattagagg tcacgtgagt gttttgcgac attttgcgac accatgtggt 60cacgctgggt atttaagccc gagtgagcac gcagggtctc cattttgaag cgggaggttt 120gaacgcgcag ccgccatgcc ggggttttac gagattgtga ttaaggtccc cagcgacctt 180gacgggcatc tgcccggcat ttctgacagc tttgtgaact gggtggccga gaaggaatgg 240gagttgccgc cagattctga catggatctg aatctgattg agcaggcacc cctgaccgtg 300gccgagaagc tgcagcgcga ctttctgacg gaatggcgcc gtgtgagtaa ggccccggag 360gcccttttct ttgtgcaatt tgagaaggga gagagctact tccacatgca cgtgctcgtg 420gaaaccaccg gggtgaaatc catggttttg ggacgtttcc tgagtcagat tcgcgaaaaa 480ctgattcaga gaatttaccg cgggatcgag ccgactttgc caaactggtt cgcggtcaca 540aagaccagaa atggcgccgg aggcgggaac aaggtggtgg atgagtgcta catccccaat 600tacttgctcc ccaaaaccca gcctgagctc cagtgggcgt ggactaatat ggaacagtat 660ttaagcgcct gtttgaatct cacggagcgt aaacggttgg tggcgcagca tctgacgcac 720gtgtcgcaga cgcaggagca gaacaaagag aatcagaatc ccaattctga tgcgccggtg 780atcagatcaa aaacttcagc caggtacatg gagctggtcg ggtggctcgt ggacaagggg 840attacctcgg agaagcagtg gatccaggag gaccaggcct catacatctc cttcaatgcg 900gcctccaact cgcggtccca aatcaaggct gccttggaca atgcgggaaa gattatgagc 960ctgactaaaa ccgcccccga ctacctggtg ggccagcagc ccgtggagga catttccagc 1020aatcggattt ataaaatttt ggaactaaac gggtacgatc cccaatatgc ggcttccgtc 1080tttctgggat gggccacgaa aaagttcggc aagaggaaca ccatctggct gtttgggcct 1140gcaactaccg ggaagaccaa catcgcggag gccatagccc acactgtgcc cttctacggg 1200tgcgtaaact ggaccaatga gaactttccc ttcaacgact gtgtcgacaa gatggtgatc 1260tggtgggagg aggggaagat gaccgccaag gtcgtggagt cggccaaagc cattctggga 1320ggaagcaagg tgcgcgtgga ccagaaatgc aagtcctcgg cccagataga cccgactccc 1380gtgatcgtca cctccaacac caacatgtgc gccgtgattg acgggaactc aacgaccttc 1440gaacaccagc agccgttgca agaccggatg ttcaaatttg aactcacccg ccgtctggat 1500catgactttg ggaaggtcac caagcaggaa gtcaaagact ttttccggtg ggcaaaggat 1560cacgtggttg aggtggagca tgaattctac gtcaaaaagg gtggagccaa gaaaagaccc 1620gcccccagtg acgcagatat aagtgagccc aaacgggtgc gcgagtcagt tgcgcagcca 1680tcgacgtcag acgcggaagc ttcgatcaac tacgcagaca ggtaccaaaa caaatgttct 1740cgtcacgtgg gtatgaatct gatgcttttt ccctgccggc aatgcgagag aatgaatcag 1800aatgtggaca tttgcttcac gcacggggtc atggactgtg ccgagtgctt ccccgtgtca 1860gaatctcaac ccgtgtctgt cgtcagaaag cggacgtatc agaaactgtg tccgattcat 1920cacatcatgg ggagggcgcc cgaggtggcc tgctcggcct gcgaactggc caatgtggac 1980ttggatgact gtgacatgga acaataaatg actcaaacca gatatgactg acggttacct 2040tccagattgg ctagaggaca acctctctga aggcgttcga gagtggtggg cgctgcaacc 2100tggagcccct aaacccaagg caaatcaaca acatcaggac aacgctcggg gtcttgtgct 2160tccgggttac aaatacctcg gacccggcaa cggactcgac aagggggaac ccgtcaacgc 2220agcggacgcg gcagccctcg agcacgacaa ggcctacgac cagcagctca aggccggtga 2280caacccctac ctcaagtaca accacgccga cgcggagttc cagcagcggc ttcagggcga 2340cacatcgttt gggggcaacc tcggcagagc agtcttccag gccaaaaaga gggttcttga 2400acctcttggt ctggttgagc aagcgggtga gacggctcct ggaaagaaga gaccgttgat 2460tgaatccccc cagcagcccg actcctccac gggtatcggc aaaaaaggca agcagccggc 2520taaaaagaag ctcgttttcg aagacgaaac tggagcaggc gacggacccc ctgagggatc 2580aacttccgga gccatgtctg atgacagtga gatgcgtgca gcagctggcg gagctgcagt 2640cgagggcgga caaggtgccg atggagtggg taatgcctcg ggtgattggc attgcgattc 2700cacctggtct gagggccacg tcacgaccac cagcaccaga acctgggtct tgcccaccta 2760caacaaccac ctctacaagc gactcggaga gagcctgcag tccaacacct acaacggatt 2820ctccaccccc tggggatact ttgacttcaa ccgcttccac tgccacttct caccacgtga 2880ctggcagcga ctcatcaaca acaactgggg catgcgaccc aaagccatgc gggtcaaaat 2940cttcaacatc caggtcaagg aggtcacgac gtcgaacggc gagacaacgg tggctaataa 3000ccttaccagc acggttcaga tctttgcgga ctcgtcgtac gaactgccgt acgtgatgga 3060tgcgggtcaa gagggcagcc tgcctccttt tcccaacgac gtctttatgg tgccccagta 3120cggctactgt ggactggtga ccggcaacac ttcgcagcaa cagactgaca gaaatgcctt 3180ctactgcctg gagtactttc cttcgcagat gctgcggact ggcaacaact ttgaaattac 3240gtacagtttt gagaaggtgc ctttccactc gatgtacgcg cacagccaga gcctggaccg 3300gctgatgaac cctctcatcg accagtacct gtggggactg caatcgacca ccaccggaac 3360caccctgaat gccgggactg ccaccaccaa ctttaccaag ctgcggccta ccaacttttc 3420caactttaaa aagaactggc tgcccgggcc ttcaatcaag cagcagggct tctcaaagac 3480tgccaatcaa aactacaaga tccctgccac cgggtcagac agtctcatca aatacgagac 3540gcacagcact ctggacggaa gatggagtgc cctgaccccc ggacctccaa tggccacggc 3600tggacctgcg gacagcaagt tcagcaacag ccagctcatc tttgcggggc ctaaacagaa 3660cggcaacacg gccaccgtac ccgggactct gatcttcacc tctgaggagg agctggcagc 3720caccaacgcc accgatacgg acatgtgggg caacctacct ggcggtgacc agagcaacag 3780caacctgccg accgtggaca gactgacagc cttgggagcc gtgcctggaa tggtctggca 3840aaacagagac atttactacc agggtcccat ttgggccaag attcctcata ccgatggaca 3900ctttcacccc tcaccgctga ttggtgggtt tgggctgaaa cacccgcctc ctcaaatttt 3960tatcaagaac accccggtac ctgcgaatcc tgcaacgacc ttcagctcta ctccggtaaa 4020ctccttcatt actcagtaca gcactggcca ggtgtcggtg cagattgact gggagatcca 4080gaaggagcgg tccaaacgct ggaaccccga ggtccagttt acctccaact acggacagca 4140aaactctctg ttgtgggctc ccgatgcggc tgggaaatac actgagccta gggctatcgg 4200tacctgcgaa tccttcgacc accttcagtg cggcaaagtt tgcttccttc atcacacagt 4260actccacggg acacggtcag cgtggagatc gagtgggagc tgcagaagga aaacagcaaa 4320cgctggaatc ccgaaattca gtacacttcc aactacaaca agtctgttaa tcgtggactt 4380accgtggata ctaatggcgt gtattcagag cctcgcccca ttggcaccag atacctgact 4440cgtaatctgt aattgcttgt taatcaataa accgtttaat tcgtttcagt tgaactttgg 4500tctctgcgta tttctttctt atctagtttc catgct 4536 <212> Type: DNA <211> Length: 4536...

SequenceName：r2c4

SequenceDescription: Custom Codon ------------ Sequence Name: r2c4SEQ ID NO.4: [Electronic version File name: r2c5 (Seq4). WorkFile] Sequence Name: seq1: rep (AAV2)-cap ( AAV1) <400> PreSequenceString: ctagagtcct gtattagagg tcacgtgagt gttttgcgac attttgcgac accatgtggt 60cacgctgggt atttaagccc gagtgagcac gcagggtctc cattttgaag cgggaggttt 120gaacgcgcag ccgccatgcc ggggttttac gagattgtga ttaaggtccc cagcgacctt 180gacgggcatc tgcccggcat ttctgacagc tttgtgaact gggtggccga gaaggaatgg 240gagttgccgc cagattctga catggatctg aatctgattg agcaggcacc cctgaccgtg 300gccgagaagc tgcagcgcga ctttctgacg gaatggcgcc gtgtgagtaa ggccccggag 360gcccttttct ttgtgcaatt tgagaaggga gagagctact tccacatgca cgtgctcgtg 420gaaaccaccg gggtgaaatc catggttttg ggacgtttcc tgagtcagat tcgcgaaaaa 480ctgattcaga gaatttaccg cgggatcgag ccgactttgc caaactggtt cgcggtcaca 540aagaccagaa atggcgccgg aggcgggaac aaggtggtgg atgagtgcta catccccaat 600tacttgctcc ccaaaaccca gcctgagctc cagtgggcgt ggactaatat ggaacagtat 660ttaagcgcct gtttgaatct cacggagcgt aaacggttgg tggcgcagca tctgacgcac 720gtgtcgcaga cgcaggagca gaacaaagag aatcagaatc ccaattctga tgcgccggtg 780atcagatcaa aaacttcagc caggtacatg gagctggtcg ggtggctcgt ggacaagggg 840attacctcgg agaagcagtg gatccaggaa aatcaggaga gctacctctc cttcaactcc 900accggcaact ctcggagcca gatcaaggcc gcgctcgaca acgcgaccaa aattatgagt 960ctgacaaaaa gcgcggtgga ctacctcgtg gggagctccg ttcccgagga catttcaaaa 1020aacagaatct ggcaaatttt tgagatgaat ggctacgacc cggcctacgc gggttccatc 1080ctctacggct ggtgtcagcg ctccttcaac aagaggaaca ccgtctggct ctacggaccc 1140gccacgaccg gcaagaccaa catcgcggag gccatcgccc acactgtgcc cttttacggc 1200tgcgtgaact ggaccaatga aaactttccc tttaatgact gtgtggacaa aatgctcatt 1260tggtgggagg agggaaagat gaccaacaag gtggttgaat ccgccaaggc catcctgggg 1320ggctcaaagg tgcgggtcga tcagaaatgt aaatcctctg ttcaaattga ttctacccct 1380gtcattgtaa cttccaatac aaacatgtgt gtggtggtgg atgggaattc cacgaccttt 1440gaacaccagc agccgctgga ggaccgcatg ttcaaatttg aactgactaa gcggctcccg 1500ccagattttg gcaagattac taagcaggaa gtcaaggact tttttgcttg ggcaaaggtc 1560aatcaggtgc cggtgactca cgagtttaaa gttcccaggg aattggcggg aactaaaggg 1620gcggagaaat ctctaaaacg cccactgggt gacgtcacca atactagcta taaaagtctg 1680gagaagcggg ccaggctctc atttgttccc gagacgcctc gcagttcaga cgtgactgtt 1740gatcccgctc ctctgcgacc gctcaattgg aattcaaggt atgattgcaa atgtgactat 1800catgctcaat ttgacaacat ttctaacaaa tgtgatgaat gtgaatattt gaatcggggc 1860aaaaatggat gtatctgtca caatgtaact cactgtcaaa tttgtcatgg gattcccccc 1920tgggaaaagg aaaacttgtc agattttggg gattttgacg atgccaataa agaacagtaa 1980ataaagcgag tagtcatgtc ttttgttgat caccctccag attggttgga agaagttggt 2040gaaggtcttc gcgagttttt gggccttgaa gcgggcccac cgaaaccaaa acccaatcag 2100cagcatcaag atcaagcccg tggtcttgtg ctgcctggtt ataactatct cggacccgga 2160aacggtctcg atcgaggaga gcctgtcaac agggcagacg aggtcgcgcg agagcacgac 2220atctcgtaca acgagcagct tgaggcggga gacaacccct acctcaagta caaccacgcg 2280gacgccgagt ttcaggagaa gctcgccgac gacacatcct tcgggggaaa cctcggaaag 2340gcagtctttc aggccaagaa aagggttctc gaaccttttg gcctggttga agagggtgct 2400aagacggccc ctaccggaaa gcggatagac gaccactttc caaaaagaaa gaaggctcgg 2460accgaagagg actccaagcc ttccacctcg tcagacgccg aagctggacc cagcggttcc 2520cagcagctgc aaatcccagc ccaaccagcc tcaagtttgg gagctgatac aatgtctgcg 2580ggaggtggcg gcccattggg cgacaataac caaggtgccg atggagtggg caatgcctcg 2640ggagattggc attgcgattc cacgtggatg ggggacagag tcgtcaccaa gtccacccga 2700acctgggtgc tgcccagcta caacaaccac cagtaccgag agatcaaaag cggctccgtc 2760gacggaagca acgccaacgc ctactttgga tacagcaccc cctgggggta ctttgacttt 2820aaccgcttcc acagccactg gagcccccga gactggcaaa gactcatcaa caactactgg 2880ggcttcagac cccggtccct cagagtcaaa atcttcaaca ttcaagtcaa agaggtcacg 2940gtgcaggact ccaccaccac catcgccaac aacctcacct ccaccgtcca agtgtttacg 3000gacgacgact accagctgcc ctacgtcgtc ggcaacggga ccgagggatg cctgccggcc 3060ttccctccgc aggtctttac gctgccgcag tacggttacg cgacgctgaa ccgcgacaac 3120acagaaaatc ccaccgagag gagcagcttc ttctgcctag agtactttcc cagcaagatg 3180ctgagaacgg gcaacaactt tgagtttacc tacaactttg aggaggtgcc cttccactcc 3240agcttcgctc ccagtcagaa cctcttcaag ctggccaacc cgctggtgga ccagtacttg 3300taccgcttcg tgagcacaaa taacactggc ggagtccagt tcaacaagaa cctggccggg 3360agatacgcca acacctacaa aaactggttc ccggggccca tgggccgaac ccagggctgg 3420aacctgggct ccggggtcaa ccgcgccagt gtcagcgcct tcgccacgac caataggatg 3480gagctcgagg gcgcgagtta ccaggtgccc ccgcagccga acggcatgac caacaacctc 3540cagggcagca acacctatgc cctggagaac actatgatct tcaacagcca gccggcgaac 3600ccgggcacca ccgccacgta cctcgagggc aacatgctca tcaccagcga gagcgagacg 3660cagccggtga accgcgtggc gtacaacgtc ggcgggcaga tggccaccaa caaccagagc 3720tccaccactg cccccgcgac cggcacgtac aacctccagg aaatcgtgcc cggcagcgtg 3780tggatggaga gggacgtgta cctccaagga cccatctggg ccaagatccc agagacgggg 3840gcgcactttc acccctctcc ggccatgggc ggattcggac tcaaacaccc accgcccatg 3900atgctcatca agaacacgcc tgtgcccgga aatatcacca gcttctcgga cgtgcccgtc 3960agcagcttca tcacccagta cagcaccggg caggtcaccg tggagatgga gtgggagctc 4020aagaaggaaa actccaagag gtggaaccca gagatccagt acacaaacaa ctacaacgac 4080ccccagtttg tggactttgc cccggacagc accggggaat acagaaccac cagacctatc 4140ggaacccgat accttacccg acccctttaa cccattcatg tcgcataccc tcaataaacc 4200gtgtattcgt gtcagtaaaa tactgcctct tgtggtcatt caatgaataa cagcttacaa 4260catctacaaa acctccttgc ttgagagtgt ggcactctcc cccctgtcgc gcgt 4314 <212> Type: DNA <211> Length : 4314...

SequenceName：r2c5

SequenceDescription: Custom Codon ------------ Sequence Name: r2c5SEQ ID NO.5: [Electronic version File name: r2c6 (Seq5). WorkFile] Sequence Name: seq1: rep (AAV2)-cap ( AAV1) <400> PreSequenceString: ctagagtcct gtattagagg tcacgtgagt gttttgcgac attttgcgac accatgtggt 60cacgctgggt atttaagccc gagtgagcac gcagggtctc cattttgaag cgggaggttt 120gaacgcgcag ccgccatgcc ggggttttac gagattgtga ttaaggtccc cagcgacctt 180gacgggcatc tgcccggcat ttctgacagc tttgtgaact gggtggccga gaaggaatgg 240gagttgccgc cagattctga catggatctg aatctgattg agcaggcacc cctgaccgtg 300gccgagaagc tgcagcgcga ctttctgacg gaatggcgcc gtgtgagtaa ggccccggag 360gcccttttct ttgtgcaatt tgagaaggga gagagctact tccacatgca cgtgctcgtg 420gaaaccaccg gggtgaaatc catggttttg ggacgtttcc tgagtcagat tcgcgaaaaa 480ctgattcaga gaatttaccg cgggatcgag ccgactttgc caaactggtt cgcggtcaca 540aagaccagaa atggcgccgg aggcgggaac aaggtggtgg atgagtgcta catccccaat 600tacttgctcc ccaaaaccca gcctgagctc cagtgggcgt ggactaatat ggaacagtat 660ttaagcgcct gtttgaatct cacggagcgt aaacggttgg tggcgcagca tctgacgcac 720gtgtcgcaga cgcaggagca gaacaaagag aatcagaatc ccaattctga tgcgccggtg 780atcagatcaa aaacttcagc caggtacatg gagctggtcg ggtggctcgt ggacaagggg 840attacctcgg agaagcagtg gatccaggag gaccaggcct catacatctc cttcaatgcg 900gcctccaact cgcggtccca aatcaaggct gccttggaca atgcgggaaa gattatgagc 960ctgactaaaa ccgcccccga ctacctggtg ggccagcagc ccgtggagga catttccagc 1020aatcggattt ataaaatttt ggaactaaac gggtacgatc cccaatatgc ggcttccgtc 1080tttctgggat gggccacgaa aaagttcggc aagaggaaca ccatctggct gtttgggcct 1140gcaactaccg ggaagaccaa catcgcggag gccatagccc acactgtgcc cttctacggg 1200tgcgtaaact ggaccaatga gaactttccc ttcaacgact gtgtcgacaa gatggtgatc 1260tggtgggagg aggggaagat gaccgccaag gtcgtggagt cggccaaagc cattctggga 1320ggaagcaagg tgcgcgtgga ccagaaatgc aagtcctcgg cccagataga cccgactccc 1380gtgatcgtca cctccaacac caacatgtgc gccgtgattg acgggaactc aacgaccttc 1440gaacaccagc agccgttgca agaccggatg ttcaaatttg aactcacccg ccgtctggat 1500catgactttg ggaaggtcac caagcaggaa gtcaaagact ttttccggtg ggcaaaggat 1560cacgtggttg aggtggagca tgaattctac gtcaaaaagg gtggagccaa gaaaagaccc 1620gcccccagtg acgcagatat aagtgagccc aaacgggtgc gcgagtcagt tgcgcagcca 1680tcgacgtcag acgcggaagc ttcgatcaac tacgcagaca ggtaccaaaa caaatgttct 1740cgtcacgcgg gcatgcttca gatgctgttt ccctgcaaaa catgcgagag aatgaatcag 1800aatttcaaca tttgcttcac gcacgggacc agagactgtt cagaatgttt ccccggcgtg 1860tcagaatctc aaccggtcgt cagaaagagg acgtatcgga aactctgtgc cattcatcat 1920ctgctggggc gggctcccga gattgcttgc tcggcctgcg atctggtcaa cgtggatctg 1980gatgactgtg tttctgagca ataaatgact taaaccaggt atggctgccg atggttatct 2040tccagattgg ctcgaggaca acctctctga gggcattcgc gagtggtggg acttgaaacc 2100tggagccccg aaacccaaag ccaaccagca aaagcaggac gacggccggg gtctggtgct 2160tcctggctac aagtacctcg gacccttcaa cggactcgac aagggggagc ccgtcaacgc 2220ggcggatgca gcggccctcg agcacgacaa ggcctacgac cagcagctca aagcgggtga 2280caatccgtac ctgcggtata accacgccga cgccgagttt caggagcgtc tgcaagaaga 2340tacgtctttt gggggcaacc tcgggcgagc agtcttccag gccaagaaga gggttctcga 2400accttttggt ctggttgagg aaggtgctaa gacggctcct ggaaagaaac gtccggtaga 2460gcagtcgcca caagagccag actcctcctc gggcattggc aagacaggcc agcagcccgc 2520taaaaagaga ctcaattttg gtcagactgg cgactcagag tcagtccccg acccacaacc 2580tctcggagaa cctccagcaa cccccgctgc tgtgggacct actacaatgg cttcaggcgg 2640tggcgcacca atggcagaca ataacgaagg cgccgacgga gtgggtaatg cctcaggaaa 2700ttggcattgc gattccacat ggctgggcga cagagtcatc accaccagca cccgaacatg 2760ggccttgccc acctataaca accacctcta caagcaaatc tccagtgctt caacgggggc 2820cagcaacgac aaccactact tcggctacag caccccctgg gggtattttg atttcaacag 2880attccactgc catttctcac cacgtgactg gcagcgactc atcaacaaca attggggatt 2940ccggcccaag agactcaact tcaagctctt caacatccaa gtcaaggagg tcacgacgaa 3000tgatggcgtc acgaccatcg ctaataacct taccagcacg gttcaagtct tctcggactc 3060ggagtaccag ttgccgtacg tcctcggctc tgcgcaccag ggctgcctcc ctccgttccc 3120ggcggacgtg ttcatgattc cgcagtacgg ctacctaacg ctcaacaatg gcagccaggc 3180agtgggacgg tcatcctttt actgcctgga atatttccca tcgcagatgc tgagaacggg 3240caataacttt accttcagct acaccttcga ggacgtgcct ttccacagca gctacgcgca 3300cagccagagc ctggaccggc tgatgaatcc tctcatcgac cagtacctgt attacctgaa 3360cagaactcag aatcagtccg gaagtgccca aaacaaggac ttgctgttta gccgggggtc 3420tccagctggc atgtctgttc agcccaaaaa ctggctacct ggaccctgtt accggcagca 3480gcgcgtttct aaaacaaaaa cagacaacaa caacagcaac tttacctgga ctggtgcttc 3540aaaatataac cttaatgggc gtgaatctat aatcaaccct ggcactgcta tggcctcaca 3600caaagacgac aaagacaagt tctttcccat gagcggtgtc atgatttttg gaaaggagag 3660cgccggagct tcaaacactg cattggacaa tgtcatgatc acagacgaag aggaaatcaa 3720agccactaac cccgtggcca ccgaaagatt tgggactgtg gcagtcaatc tccagagcag 3780cagcacagac cctgcgaccg gagatgtgca tgttatggga gccttacctg gaatggtgtg 3840gcaagacaga gacgtatacc tgcagggtcc tatttgggcc aaaattcctc acacggatgg 3900acactttcac ccgtctcctc tcatgggcgg ctttggactt aagcacccgc ctcctcagat 3960cctcatcaaa aacacgcctg ttcctgcgaa tcctccggca gagttttcgg ctacaaagtt 4020tgcttcattc atcacccagt attccacagg acaagtgagc gtggagattg aatgggagct 4080gcagaaagaa aacagcaaac gctggaatcc cgaagtgcag tatacatcta actatgcaaa 4140atctgccaac gttgatttca ctgtggacaa caatggactt tatactgagc ctcgccccat 4200tggcacccgt tacctcaccc gtcccctgta attgtgtgt 4239 <212> Type: DNA <211> Length: 4239...

SequenceName：r2c6

SequenceDescription: Custom Codon ------------ Sequence Name: r2c5SEQ ID NO.5: [Electronic version File name: r2c6 (Seq5). WorkFile] Sequence Name: seq1: rep (AAV2)-cap ( AAV1) <400> PreSequenceString: ctagagtcct gtattagagg tcacgtgagt gttttgcgac attttgcgac accatgtggt 60cacgctgggt atttaagccc gagtgagcac gcagggtctc cattttgaag cgggaggttt 120gaacgcgcag ccgccatgcc ggggttttac gagattgtga ttaaggtccc cagcgacctt 180gacgggcatc tgcccggcat ttctgacagc tttgtgaact gggtggccga gaaggaatgg 240gagttgccgc cagattctga catggatctg aatctgattg agcaggcacc cctgaccgtg 300gccgagaagc tgcagcgcga ctttctgacg gaatggcgcc gtgtgagtaa ggccccggag 360gcccttttct ttgtgcaatt tgagaaggga gagagctact tccacatgca cgtgctcgtg 420gaaaccaccg gggtgaaatc catggttttg ggacgtttcc tgagtcagat tcgcgaaaaa 480ctgattcaga gaatttaccg cgggatcgag ccgactttgc caaactggtt cgcggtcaca 540aagaccagaa atggcgccgg aggcgggaac aaggtggtgg atgagtgcta catccccaat 600tacttgctcc ccaaaaccca gcctgagctc cagtgggcgt ggactaatat ggaacagtat 660ttaagcgcct gtttgaatct cacggagcgt aaacggttgg tggcgcagca tctgacgcac 720gtgtcgcaga cgcaggagca gaacaaagag aatcagaatc ccaattctga tgcgccggtg 780atcagatcaa aaacttcagc caggtacatg gagctggtcg ggtggctcgt ggacaagggg 840attacctcgg agaagcagtg gatccaggag gaccaggcct catacatctc cttcaatgcg 900gcctccaact cgcggtccca aatcaaggct gccttggaca atgcgggaaa gattatgagc 960ctgactaaaa ccgcccccga ctacctggtg ggccagcagc ccgtggagga catttccagc 1020aatcggattt ataaaatttt ggaactaaac gggtacgatc cccaatatgc ggcttccgtc 1080tttctgggat gggccacgaa aaagttcggc aagaggaaca ccatctggct gtttgggcct 1140gcaactaccg ggaagaccaa catcgcggag gccatagccc acactgtgcc cttctacggg 1200tgcgtaaact ggaccaatga gaactttccc ttcaacgact gtgtcgacaa gatggtgatc 1260tggtgggagg aggggaagat gaccgccaag gtcgtggagt cggccaaagc cattctggga 1320ggaagcaagg tgcgcgtgga ccagaaatgc aagtcctcgg cccagataga cccgactccc 1380gtgatcgtca cctccaacac caacatgtgc gccgtgattg acgggaactc aacgaccttc 1440gaacaccagc agccgttgca agaccggatg ttcaaatttg aactcacccg ccgtctggat 1500catgactttg ggaaggtcac caagcaggaa gtcaaagact ttttccggtg ggcaaaggat 1560cacgtggttg aggtggagca tgaattctac gtcaaaaagg gtggagccaa gaaaagaccc 1620gcccccagtg acgcagatat aagtgagccc aaacgggtgc gcgagtcagt tgcgcagcca 1680tcgacgtcag acgcggaagc ttcgatcaac tacgcagaca ggtaccaaaa caaatgttct 1740cgtcacgcgg gcatgcttca gatgctgttt ccctgcaaaa catgcgagag aatgaatcag 1800aatttcaaca tttgcttcac gcacgggacc agagactgtt cagaatgttt ccccggcgtg 1860tcagaatctc aaccggtcgt cagaaagagg acgtatcgga aactctgtgc cattcatcat 1920ctgctggggc gggctcccga gattgcttgc tcggcctgcg atctggtcaa cgtggatctg 1980gatgactgtg tttctgagca ataaatgact taaaccaggt atggctgccg atggttatct 2040tccagattgg ctcgaggaca acctctctga gggcattcgc gagtggtggg acttgaaacc 2100tggagccccg aaacccaaag ccaaccagca aaagcaggac gacggccggg gtctggtgct 2160tcctggctac aagtacctcg gacccttcaa cggactcgac aagggggagc ccgtcaacgc 2220ggcggatgca gcggccctcg agcacgacaa ggcctacgac cagcagctca aagcgggtga 2280caatccgtac ctgcggtata accacgccga cgccgagttt caggagcgtc tgcaagaaga 2340tacgtctttt gggggcaacc tcgggcgagc agtcttccag gccaagaaga gggttctcga 2400accttttggt ctggttgagg aaggtgctaa gacggctcct ggaaagaaac gtccggtaga 2460gcagtcgcca caagagccag actcctcctc gggcattggc aagacaggcc agcagcccgc 2520taaaaagaga ctcaattttg gtcagactgg cgactcagag tcagtccccg acccacaacc 2580tctcggagaa cctccagcaa cccccgctgc tgtgggacct actacaatgg cttcaggcgg 2640tggcgcacca atggcagaca ataacgaagg cgccgacgga gtgggtaatg cctcaggaaa 2700ttggcattgc gattccacat ggctgggcga cagagtcatc accaccagca cccgaacatg 2760ggccttgccc acctataaca accacctcta caagcaaatc tccagtgctt caacgggggc 2820cagcaacgac aaccactact tcggctacag caccccctgg gggtattttg atttcaacag 2880attccactgc catttctcac cacgtgactg gcagcgactc atcaacaaca attggggatt 2940ccggcccaag agactcaact tcaagctctt caacatccaa gtcaaggagg tcacgacgaa 3000tgatggcgtc acgaccatcg ctaataacct taccagcacg gttcaagtct tctcggactc 3060ggagtaccag ttgccgtacg tcctcggctc tgcgcaccag ggctgcctcc ctccgttccc 3120ggcggacgtg ttcatgattc cgcagtacgg ctacctaacg ctcaacaatg gcagccaggc 3180agtgggacgg tcatcctttt actgcctgga atatttccca tcgcagatgc tgagaacggg 3240caataacttt accttcagct acaccttcga ggacgtgcct ttccacagca gctacgcgca 3300cagccagagc ctggaccggc tgatgaatcc tctcatcgac cagtacctgt attacctgaa 3360cagaactcag aatcagtccg gaagtgccca aaacaaggac ttgctgttta gccgggggtc 3420tccagctggc atgtctgttc agcccaaaaa ctggctacct ggaccctgtt accggcagca 3480gcgcgtttct aaaacaaaaa cagacaacaa caacagcaac tttacctgga ctggtgcttc 3540aaaatataac cttaatgggc gtgaatctat aatcaaccct ggcactgcta tggcctcaca 3600caaagacgac aaagacaagt tctttcccat gagcggtgtc atgatttttg gaaaggagag 3660cgccggagct tcaaacactg cattggacaa tgtcatgatc acagacgaag aggaaatcaa 3720agccactaac cccgtggcca ccgaaagatt tgggactgtg gcagtcaatc tccagagcag 3780cagcacagac cctgcgaccg gagatgtgca tgttatggga gccttacctg gaatggtgtg 3840gcaagacaga gacgtatacc tgcagggtcc tatttgggcc aaaattcctc acacggatgg 3900acactttcac ccgtctcctc tcatgggcgg ctttggactt aagcacccgc ctcctcagat 3960cctcatcaaa aacacgcctg ttcctgcgaa tcctccggca gagttttcgg ctacaaagtt 4020tgcttcattc atcacccagt attccacagg acaagtgagc gtggagattg aatgggagct 4080gcagaaagaa aacagcaaac gctggaatcc cgaagtgcag tatacatcta actatgcaaa 4140atctgccaac gttgatttca ctgtggacaa caatggactt tatactgagc ctcgccccat 4200tggcacccgt tacctcaccc gtcccctgta attgtgtgt 4239 <212> Type: DNA <211> Length: 4239...

SequenceName：cos6

SequenceDescription: Custom Codon ------------ Sequence Name: cos6 Seq7: [Electronic version File name: cos14 (Seq7). WorkFile] Sequence Name: cos14 Sequence -------- <213> OrganismName: Human herpes simplex virus type 1 <400> PreSequenceString: gatcagaaag cccccattgg ccaggtagta ctgcggctgg cccaccttga tgtgcgtcgc 60 gttgtacctg cgggcgaaga tgcggtccat ggcgtcgcgg gcgtccttgc cgatgcagtc 120 ccccaggtcc acgcgcgaga gcgggtactc ggtcaggttg gtggtgaagg tggtggatat 180 ggcgtcggaa gagaatcgga aggagccgcc gtactcggag cgcagcatct cgtccacctc 240 ctgccacttg gtcatggtgc agaccgacgg gcgctttggc acccagtccc aggccacggt 300 gaacttgggg gtcgtgagca ggttccgggt ggtcggcgcc gtggcccggg ccttggtggt 360 gaggtcgcgc gcgtagaagc cgtcgacctg cttgaagcgg tcggcggcgt agctggtgtg 420 ttcggtgtgc gacccctccc ggtagccgta aaacggggac atgtacacaa agtcgccagt 480 cgccaacaca aactcgtcgt acgggtacac cgagcgcgcg tccacctcct cgacgatgca 540 gtttaccgtc gtcccgtacc ggtggaacgc ctccacccgc gaggggttgt acttgaggtc 600 ggtggtgtgc cagccccggc tcgtgcgggt cgcggcgttg gccggtttca gctccatgtc 660 ggtctcgtgg tcgtcccggt gaaacgcggt ggtctccagg ttgttgcgca cgtacttggc 720 cgtggaccga cagaccccct tggcgttgat cttgtcgatc acctcctcga aggggacggg 780 ggcgcggtcc tcaaagatcc ccataaactg ggagtagcgg tggccgaacc acacctgcga 840 aacggtgacg tctttgtagt acatggtggc cttgaacttg tacggggcga tgttctcctt 900 gaagaccacc gcgatgccct ccgtgtagtt ctgaccctcg ggccgggtcg ggcagcggcg 960 cggctgctcg aactgcacca ccgtggcgcc cgtggggggt gggcacacgt aaaagtttgc 1020 atcggtgttc tccgccttga tgtcccgcag gtgctcgcgc agggtggcgt ggcccgcggc 1080 gacggtcgcg ttgtcgccgg cggggcgcgg cggctttggg ggtttcggtt ttctgttctt 1140 cttcggtttc gggtcccccg ttgggggggc gccaggggcg ggcggcgccg gagtggcagg 1200 gcccccgttc gccgcctggg tcgcggccgc gaccccaggc gtgccggggg aactcggagc 1260 cgccgacgcc accaggaccc ccagcgtcaa ccccaagagc gcccatacga cgaaccaccg 1320 gcgcccccgc gcgggggcgc cctggcgcat ggcgggacta cgggggcccg tcgtgccccc 1380 cgtcaggtag cctgggggcg aggtgctgga ggaccgagta gaggatcgag aaaacgtctc 1440 ggtcgtagac cacgaccgac cgggggccga tacagccgtc gggggcgctc tcgacgatgg 1500 ccaccagcgg acagtcggag tcgtacgtga gatatacgcc gggcgggtaa cggtaacgac 1560 cttcggaggt cgggcggctg cagtccgggc ggcgcaactc gagctccccg caccggtaga 1620 ccgaggcaaa gagtgtggtg gcgataatca gctcgcgaat atatcgccag gcggcgcgct 1680 gagtgggcgt tattccggaa atgccgtcaa aacagtaaaa cctctgaaat tcgctgacgg 1740 cccaatcagc acccgagccc cccgccccca tgatgaaccg ggcgagctcc tccttcaggt 1800 gcggcaggag ccccacgttc tcgacgctgt aatacagcgc ggtgttgggg ggctgggcga 1860 agctgtgggt ggagtgatca aagaggggcc cgttgacgag ctcgaagaag cgatgggtga 1920 tgctggggag cagggccggg tccacctggt gtcgcaggag agacgctcgc atgaaccggt 1980 gcgcgtcgaa cacgcccggc gccgagcggt tgtcgatgac cgtgcccgcg cccgccgtca 2040 gggcgcagaa gcgcgcgcgc gccgcaaagc cgttggcgac cgcggcgaac gtcgcgggca 2100 gcacctcgcc gtggacgctg acccgcagca tcttctcgag ctccccgcgc tgctcgcgga 2160 cgcagcgccc caggctggcc aacgaccgct tcgtcaggcg gtccgcgtac agccgccgtc 2220 gctcccgcac gtccgcggcc gcttgcgtgg cgatgtcccc ccacgtctcg ggcccctgcc 2280 ccccgggccc gcggcgacgg tcttcgtcct cgcccccgcc cccgggagct cccaaccccc 2340 gtgccccttc ctctacggcg acacggtccc cgtcgtcgtc ggggcccgcg ccgcccttgg 2400 gcgcgtccgc cgcgcccccc gcccccatgc gcgccagcac gcgacgcagc gcctcctcgt 2460 cgcactgttc ggggctgacg aggcgccgca agagcggcgt cgtcaggtgg tggtcgtagc 2520 acgcgcggat gagcgcctcg atctgatcgt cgggtgacgt ggcctgaccg ccgattatta 2580 gggcgtccac catatccagc gccgccaggt ggctcccgaa cgcgcgatcg aaatgctccg 2640 cccgccgccc gaacagcgcc agttccacgg ccaccgcggc ggtctcctgc tgcaactcgc 2700 gccgcgccag cgcggtcagg ttgctggcaa acgcgtccat ggtggtctgg ccggcgcggt 2760 cgccggacgc gagccagaat cgcaattcgc tgatggcgta caggccgggc gtggtggcct 2820 gaaacacgtc gtgcgcctcc agcagggcgt cggcctcctt gcggaccgag tcgttctcgg 2880 gcgacgggtg gggctgcccg tcgccccccg cggtccgggc cagcgcatgg tccaacacgg 2940 agagcgcccg cgcgcggtcg gcgtccgaca gcccggcggc gtggggcagg taccgccgca 3000 gctcgttggc gtccagccgc acctgcgcct gctgggtgac gtggttacag atacggtccg 3060 ccaggcggcg ggcgatcgtc gccccctggt tcgccgtcac acacagttcc tcgaaacaga 3120 ccgcgcaggg gtgggacggg tcgctaagct ccggggggac gataaggccc gaccccaccg 3180 cccccaccat aaactcccga acgcgctcca gcgcggcggt ggcgccgcgc gagggggtga 3240 tgaggtggca gtagtttagc tgctttagaa agttctcgac gtcgtgcagg aaacacagct 3300 ccatatggac ggtcccgcca tacgtatcca gcctgacccg ttggtgatac ggacagggtc 3360 gggccaggcc catggtctcc gtgaaaaacg ccgcgacgtc tcccgcggtc gcgaacgtct 3420 ccaggctgcc caggagccgc tcgccctcgc gccacgcgta ctctagcagc aactccaggg 3480 tgaccgacag cggggtgaga aaggccccgg cctgggcctc caggcccggc ctcagacgac 3540 gccgcagcgc ccgcacctga agcgcgttca gcttcagttg ggggagcttc ccccgtccga 3600 tgtgggggtc gcaccgccgg agcagctcta tctgaaacac ataggtctgc acctgcccga 3660 gcagggctaa caacttttga cgggccacgg tgggctcgga caccggggcg gccatctcgc 3720 ggcgccgatc tgtaccgcgg ccggagtatg cggtggaccg aggcggtccg tacgctaccc 3780 ggcgtctggc tgagccccgg ggtccccctc ttcggggcgg cctcccgcgg gcccgccgac 3840 cggcaagccg ggagtcggcg gcgcgtgcgt ttctgctcta ttcccagaca ccgcggagag 3900 gaatcacggc ccgcccagag atatagacac ggaacacaaa caagcacgga tgtcgtagca 3960 ataatttatt ttacacacat tccccgcccc gccctaggtt cccccacccc ccaacccctc 4020 acagcatatc caacgtcagg tctccctttt tgtcgggggg cccctcccca aacgggtcat 4080 ccccgtggaa cgcccgtttg cggccggcaa atgccggtcc cggggccccc gggccgccga 4140 acggcgtcgc gttgtcgtcc tcgcagccaa aatccccaaa gttaaacacc tccccggcgt 4200 tgccgagttg gctgactagg gcctcggcct cgtgcgccac ctccagggcc gcgtccgtcg 4260 accactcgcc gttgccgcgc tccagggcac gcgcggtcag ctccatcatc tcctcgctta 4320 ggtactcgtc ctccaggagc gccagccagt cctcgatctg cagctgctgg gtgcggggcc 4380 ccaggctttt cacggtcgcc acgaacacgc tactggcgac ggccgccccg ccctcggaga 4440 taatgccccg gagctgctcg cacagcgagc tttcgtgcgc tccgccgccg aggcttgagg 4500 ccgcgcacac aaacccggcc cggggacagg ccaggacgaa cttgcgggtg cggtcaaaaa 4560 taaggagcgg gcacgcgttt ttgccgccca tcaggctggc ccagttcccg gcctgaaaca 4620 cacggtcgtt gccggccatg ccgtagtact tgctgatgct caaccccaac acgaccatgg 4680 ggcgcgccgc catgacgggc cgcagcaggt tgcagctggc gaacatggac gtccacgcgc 4740 ccggatgcgc gtccacggcg tccatcagcg cgcgggcccc ggcctccagg cccgccccgc 4800 cctgcgcgga ccacgcggcc gcagcctgca cgctgggggg acggcgggac cccgcgatga 4860 tggccgtaag ggtgttgatg aagtatgtcg agtgatcgca gtaccgcaga atctggtttg 4920 ccatgtagta catcgccagc tcgctcacgt tgttgggggc caggttaata aagtttatcg 4980 cgccgtagtc cagggaaaac tttttaatga acgcgatggt ctcgatgtcc tcgcgcgaca 5040 ggagccgggc gggaagctgg ttgcgttgga gggccgtcca gaaccactgc gggttcggct 5100 ggttggaccc cgggggcttg ccgttgggga agatggccgc gtggaactgc ttcagcagaa 5160 agcccagcgg tccgaggagg atgtccacgc gcttgtcggg cttctggtag gcgctctgga 5220 ggctggcgac ccgcgccttg gcggcctcgg acgcgttggc gctcgcgccc gcgaacaaca 5280 cgcggctctt gacgcgcagc tccttgggaa accccagggt cacgcgggca acgtcgccct 5340 cgaagctgct ctcggcgggg gccgtctggc cggccgttag gctgggggcg cagatagccg 5400 ccccctccga gagcgcgacc gtcagcgttt tggccgacag aaacccgttg ttaaacatgt 5460 ccatcacgcg ccgccgcagc accggttgga attgattgcg aaagttgcgc ccctcgaccg 5520 actgcccggc gaacaccccg tggcactgac tcagggccag gtcctggtac acggcgaggt 5580 tggatcgccg cccgagaagc tgaagcaggg ggcacggccc gcacgcgtac gggtccagcg 5640 tcagggacat ggcgtggttg gcctcgccca gaccgtcgcg aaacttgaag ttcctcccct 5700 ccaccaggtt gcgcatcagc tgctccacct cgcggtccac gacctgcctg acgttgttca 5760 ccaccgtatg cagggcctcg cggttggtga tgatggtctc cagccgcccc atggccgtgg 5820 ggaccgcctg gtccacgtac tgcagggtct cgagttcggc catgacgcgc tcggtcgccg 5880 cgcggtacgt ctcctgcatg atggtccggg cggtctcgga tccgtccgcg cgcttcaggg 5940 ccgagaaggc ggcgtagttt cccagcacgt cgcagtcgct gtacatgctg ttcatggtcc 6000 cgaagacgcc gatggctccg cgggcggcgc tggcgaactt tggatggcgc gcccggaggc 6060 gcatgagcgt cgtgtgtacg caggcgtggc gcgtgtcgaa ggtgcatagg ttacagggca 6120 cgtcggtctg gttggagtcc gcgacgtatc gaaacacgtc catctcctgg cgcccgacga 6180 tcacggcgcc gtcgcagcgc tccaggtaaa acagcatctt ggccagcagc gccggggaaa 6240 acccacacag catggccagg tgctcgccgg caaattcctg ggttccgccg acgaggggcg 6300 cggtgggccg accctcgaac ccgggcacca cgtgtccctc gcggtccacc tgtgggttgg 6360 ccgccacgtg ggtcccgggc acgaggaaga agcggtaaaa ggagggtttg ctgtggtcct 6420 ttgggtccgc cgggccggcg tcgtccacct cggtgagatg gagggccgag ttggtgctaa 6480 ataccatggc ccccacgagt cccgcggcgc gcgccaggta cgccccgacg gcgttggcgc 6540 gggccgcggc cgtgtcctgg ccctcgaaca gcggccacgc ggagatgtcg gtgggcggct 6600 cgtcaaagac ggccatcgac acgatagact cgagggccag ggcggcgtct ccggccatga 6660 cggaggccag gcgctgttcg aacccgcccg ccgcgccctt gccgccgccg tcgcgcccgc 6720 cccgcggggt cttaccctgg ctggcttcga aggccgtgaa cgtaatgtcg gcggggaggg 6780 cggcgccctc gtggttttcg tcaaacgcca ggtgggcggc cgcgcgggcc acggcgtcca 6840 cgtttcggca tcgcagtgcc acggcggcgg gtcccacgac cgcctcgaac aggaggcggt 6900 tgagggggcg gttaaaaaac ggaagcgggt aggtaaattt ctccccgatc gatcggtggt 6960 tggcgttgaa cggctctgcg atgacacggc taaaatccgg catgaacagc tgcaacgggt 7020 acacgggtat gcggtgcacc tccgccccgc ctatggttac cttgtccgag cctcccaggt 7080 gcagaaaggt gttgttgatg cacacggcct ccttgaagcc ctcggtaacg accagataca 7140 ggagggcgcg gtccgggtcc aggccgaggc gctcacacag cgcctccccc gtcgtctcgt 7200 gtttgaggtc gccgggccgg ggggtgtagt ccgaaaagcc aaaatggcgg cgtgcccgct 7260 cgcaaagtcg cgtcaggttc ggggcctggg tgctggggtc caggtgccgg ccgccgtgaa 7320 agacgtacac ggacgagctg tagtgcgagg gcgtcagttt cagggacacc gcggtacccc 7380 cgagccccgt cgtgcgagaa cccacgacca cggccacgtt ggcctcaaag ccgctctcca 7440 cggtcaggcc cacgaccagg ggcgccacgg cgacgtcgga atcgccgctg cgtgccgaca 7500 gtaacgccag aagctcgatg ccttcggacg gacacgcgcg agcgtacacg tatcccaggg 7560 gcccgggggg gaccttgatg gtggttgccg tcttgggctt tgtctccatg tccttttgtc 7620 aatcggtccg cgaacggagg taatcccggc acgacgacgg acgcccgaca aggtatgtct 7680 cccgagcgtc aaaatccggg ggggggcggc gacggtcaag gggagggttg gagaccgggg 7740 ttggggaatg aatccctccc cttcaccgac aaccccccgg gtaaccacgg ggtcgccgat 7800 gaaccccggc ggccggcaac gcggggtccc tgcgagaggc acagatgctt acggtcaggt 7860 gctccgggtc gggtgcgtct ggtatgcggt tggtatatgt acactttacc tgggggcgtg 7920 ccggtccgcc ccagcccctc ccacgccccg cgcgtcatca gccggtgggc gtggccgcta 7980 ttataaaaaa agtgagaacg cgaagcgttc gcactttgtc ctaataatat atatattatt 8040 aggacaaagt gcgaacgctt cgcgttctca ctttttttat aatagcggcc acgcccaccg 8100 gctacgtcac tctcctgtcg gccgccggcg gtccataagc ccggccggcc gggccgacgc 8160 gaataaaccg ggccgccggc cggggcgccg cgcagcagct cgccgcccgg atccgccaga 8220 caaacaaggc ccttgcacat gccggcccgg gcgagcctgg gggtccggta attttgccat 8280 cccacccaag cggctttttg ggtttttctc ttcccccctc cccacattcc cctctttagg 8340 ggttcgggtg ggaacaaccg cgatgttttc cggtggcggc ggcccgctgt cccccggagg 8400 aaagtcggcg gccagggcgg cgtccgggtt ttttgcgccc gccggccctc gcggagccag 8460 ccggggaccc ccgccttgtt tgaggcaaaa cttttacaac ccctacctcg ccccagtcgg 8520 gacgcaacag aagccgaccg ggccaaccca gcgccatacg tactatagcg aatgcgatga 8580 atttcgattc atcgccccgc gggtgctgga cgaggatgcc cccccggaga agcgcgccgg 8640 ggtgcacgac ggtcacctca agcgcgcccc caaggtgtac tgcggggggg acgagcgcga 8700 cgtcctccgc gtcgggtcgg gcggcttctg gccgcggcgc tcgcgcctgt ggggcggcgt 8760 ggaccacgcc ccggcggggt tcaaccccac cgtcaccgtc tttcacgtgt acgacatcct 8820 ggagaacgtg gagcacgcgt acggcatgcg cgcggcccag ttccacgcgc ggtttatgga 8880 cgccatcaca ccgacgggga ccgtcatcac gctcctgggc ctgactccgg aaggccaccg 8940 ggtggccgtt cacgtttacg gcacgcggca gtacttttac atgaacaagg aggaggtcga 9000 caggcaccta caatgccgcg ccccacgaga tctctgcgag cgcatggccg cggccctgcg 9060 cgagtccccg ggcgcgtcgt tccgcggcat ctccgcggac cacttcgagg cggaggtggt 9120 ggagcgcacc gacgtgtact actacgagac gcgccccgct ctgttttacc gcgtctacgt 9180 ccgaagcggg cgtgtgctgt cgtacctgtg cgacaacttc tgcccggcca tcaagaagta 9240 cgagggtggg gtcgacgcca ccacccggtt catcctggac aaccccgggt tcgtcacctt 9300 cggctggtac cgtctcaaac cgggccggaa caacacgcta gcccagccgg cggccccgat 9360 ggccttcggg acatccagcg acgtcgagtt taactgtacg gcggacaacc tggccatcga 9420 ggggggcatg agcgacctac cggcatacaa gctcatgtgc ttcgatatcg aatgcaaggc 9480 ggggggggag gacgagctgg cctttccggt ggccgggcac ccggaggacc tggtcatcca 9540 gatatcctgt ctgctctacg acctgtccac caccgccctg gagcacgtcc tcctgttttc 9600 gctcggttcc tgcgacctcc ccgaatccca cctgaacgag ctggcggcca ggggcctgcc 9660 cacgcccgtg gttctggaat tcgacagcga attcgagatg ctgttggcct tcatgaccct 9720 tgtgaaacag tacggccccg agttcgtgac cgggtacaac atcatcaact tcgactggcc 9780 cttcttgctg gccaagctga cggacattta caaggtcccc ctggacgggt acggccgcat 9840 gaacggccgg ggcgtgtttc gcgtgtggga cataggccag agccacttcc agaagcgcag 9900 caagataaag gtgaacggca tggtgaacat cgacatgtac gggattataa ccgacaagat 9960 caagctctcg agctacaagc tcaacgccgt ggccgaagcc gtcctgaagg acaagaagaa 10020 ggacctgagc tatcgcgaca tccccgccta ctacgccgcc gggcccgcgc aacgcggggt 10080 gatcggcgag tactgcatac aggattccct gctggtgggc cagctgtttt ttaagttttt 10140 gccccatctg gagctctcgg ccgtcgcgcg cttggcgggt attaacatca cccgcaccat 10200 ctacgacggc cagcagatcc gcgtctttac gtgcctgctg cgcctggccg accagaaggg 10260 ctttattctg ccggacaccc aggggcgatt taggggcgcc gggggggagg cgcccaagcg 10320 tccggccgca gcccgggagg acgaggagcg gccagaggag gagggggagg acgaggacga 10380 acgcgaggag ggcgggggcg agcgggagcc ggagggcgcg cgggagaccg ccggcaggca 10440 cgtggggtac cagggggcca gggtccttga ccccacttcc gggtttcacg tgaaccccgt 10500 ggtggtgttc gactttgcca gcctgtaccc cagcatcatc caggcccaca acctgtgctt 10560 cagcacgctc tccctgaggg ccgacgcagt ggcgcacctg gaggcgggca aggactacct 10620 ggagatcgag gtgggggggc gacggctgtt cttcgtcaag gctcacgtgc gagagagcct 10680 cctcagcatc ctcctgcggg actggctcgc catgcgaaag cagatccgct cgcggattcc 10740 ccagagcagc cccgaggagg ccgtgctcct ggacaagcag caggccgcca tcaaggtcgt 10800 gtgtaactcg gtgtacgggt tcacgggagt gcagcacgga ctcctgccgt gcctgcacgt 10860 tgccgcgacg gtgacgacca tcggccgcga gatgctgctc gcgacccgcg agtacgtcca 10920 cgcgcgctgg gcggccttcg aacagctcct ggccgatttc ccggaggcgg ccgacatgcg 10980 cgcccccggg ccctattcca tgcgcatcat ctacggggac acggactcca tctttgtgct 11040 gtgccgcggc ctcacggccg ccgggctgac ggccgtgggc gacaagatgg cgagccacat 11100 ctcgcgcgcg ctgtttctgc cccccatcaa actcgagtgc gaaaagacgt tcaccaagct 11160 gctgctgatc gccaagaaaa agtacatcgg cgtcatctac gggggtaaga tgctcatcaa 11220 gggcgtggat ctggtgcgca aaaacaactg cgcgtttatc aaccgcacct ccagggccct 11280 ggtcgacctg ctgttttacg acgataccgt ctccggagcg gccgccgcgt tagccgagcg 11340 ccccgcggag gagtggctgg cgcgacccct gcccgaggga ctgcaggcgt tcggggccgt 11400 cctcgtagac gcccatcggc gcatcaccga cccggagagg gacatccagg actttgtcct 11460 caccgccgaa ctgagcagac acccgcgcgc gtacaccaac aagcgcctgg cccacctgac 11520 ggtgtattac aagctcatgg cccgccgcgc gcaggtcccg tccatcaagg accggatccc 11580 gtacgtgatc gtggcccaga cccgcgaggt agaggagacg gtcgcgcggc tggccgccct 11640 ccgcgagcta gacgccgccg ccccagggga cgagcccgcc ccccccgcgg ccctgccctc 11700 cccggccaag cgcccccggg agacgccgtc gcctgccgac cccccgggag gcgcgtccaa 11760 gccccgcaag ctgctggtgt ccgagctggc cgaggatccc gcatacgcca ttgcccacgg 11820 cgtcgccctg aacacggact attacttctc ccacctgttg ggggcggcgt gcgtgacatt 11880 caaggccctg tttgggaata acgccaagat caccgagagt ctgttaaaaa ggtttattcc 11940 cgaagtgtgg caccccccgg acgacgtggc cgcgcggctc cggaccgcag ggttcggggc 12000 ggtgggtgcc ggcgctacgg cggaggaaac tcgtcgaatg ttgcatagag cctttgatac 12060 tctagcatga gccccccgtc gaagctgatg tccctcattt tacaataaat gtctgcggcc 12120 gacacggtcg gaatctccgc gtccgtgggt ttctctgcgt tgcgccggac cacgagcaca 12180 aacgtgctct gccacacgtg ggcgacgaac cggtaccccg ggcacgcggt gagcatccgg 12240 tctatgagcc ggtagtgcag gtgggcggac gtgccgggaa agatgacgta cagcatgtgg 12300 cccccgtaag tggggtccgg gtaaaacaac agccgcgggt cgcacgcccc gcctccgcgc 12360 aggatcgtgt ggacgaaaaa aagctcgggt tggccaagaa tcccggccaa gaggtcctgg 12420 aggggggcgt tgtggcggtc ggccaacacg accaaggagg ccaggaaggc gcgatgctcg 12480 aatatcgtgt tgatctgctg cacgaaggcc aggattaggg cctcgcggct ggtggcggcg 12540 aaccgcccgt ctcccgcgtt gcacgcggga cagcaacccc cgatgcctag gtagtagccc 12600 atcccggaga gggtcaggca gttgtcggcc acggtctggt ccagacagaa gggcagcgag 12660 acgggagtgg tcttcaccag gggcaccgag agcgagcgca cgatggcgat ctcctcggag 12720 ggcgtctggg cgagggcggc gaaaaggccc cgatagcgct ggcgctcgtg taaacacagc 12780 tcctgtttgc gggcgtgagg cggcaggctc ttccgggagg cccgacgcac cacgcccaga 12840 gtcccgccgg ccgcagagga gcgcgaccgc cggcgctcct tgccgtgata gggcccgggc 12900 cgggagccgc ggcgatgggg gtcggtgtca tacataggta cacagggtgt gctccaggga 12960 caggagcgag atcgagtggc gtctaagcag cgcgcccgcc tcacggacaa atgtggcgag 13020 cgcggtgggc tttggtacaa atacctgata cgtcttgaag gtgtagatga gggcacgcaa 13080 cgctatgcag acacgcccct cgaactcgtt cccgcaggcc agcttggcct tgtggagcag 13140 cagctcgtcg ggatgggtgg cggggggatg gccgaacaga acccaggggt caacctccat 13200 ctccgtaatg gcgcacatgg ggtcacagaa catgtgctta aagatggcct cgggccccgc 13260 ggcccgaagc aggctcacaa accggccccc gtccccgggc tgcgtctcgg ggtcagcctc 13320 gagctggtcg acgacgggta cgatacagtc gaagaggctc gtgttgtttt ccgagtagcg 13380 gaccacggag gcccggagtc tgcgcagggc cagccagtaa gcacgcacca gtaacaggtt 13440 acacagcagg cattctccgc cggtgcgccc gcgcccccgg ccgtgtttca gcacggtggc 13500 catcagaggg cccaggtcga ggtcgggctg ggcatcgggt tcggtaaact gcgcaaagcg 13560 cggagccacg tcgcgcgtgc gtgccccgcg atgcgcttcc caggactggc ggaccgtggc 13620 gcgacgggcc tccgcggcag cgcgcagctg gggccccgac tcccagacgg cgggggtgcc 13680 ggcgaggagc aacaggacca gatccgcgta cgcccacgta tccggcgact cctccggctc 13740 gcggtccccg gcgaccgtct cgaattcccc gttgcgagcg gcggcgcgag tacagcagct 13800 gtccccgccc ccgcgccgac cctccgtgca gtccaggaga cgggcgcaat ccttccagtt 13860 catcagcgcg gtggtgagcg acggctgcgt gccggatccc gccgccgacc ccgccccctc 13920 ctcgcccccg gaggccaagg ttccgatgag ggcccgggtg gcagactgcg ccaggaacga 13980 gtagttggag tactgcacct tggcggctcc cggggagggc gagggcttgg gttgcttctg 14040 ggcatgccgc ccgggcaccc cgccgtcggt acggaagcag cagtggagaa aaaagtgccg 14100 gtggatgtcg tttatggtga gggcaaagcg tgcgaaggag ccgaccaggg tcgccttctt 14160 ggtgcgcaga aagtggcggt ccatgacgta cacaaactcg aacgcggcca cgaagatgct 14220 agcggcgcag tggggcgccc ccaggcattt ggcacagaga aacgcgtaat cggccaccca 14280 ctgaggcgag aggcggtagg tttgcttgta cagctcgatg gtgcggcaga ccagacaggg 14340 ccggtccagc gcgaaggtgt cgatggccgc cgcggaaaag ggcccggtgt ccaaaagccc 14400 ctccccacag ggatccgggg gcgggttgcg gggtcctccg cgcccgcccg aaccccctcc 14460 gtcgcccgcc cccccgcggg cccttgaggg ggcggtgacc acgtcggcgg cgacgtcctc 14520 gtcgagcgta ccgacgggcg gcacacctat cacgtgactg gccgtcagga gctcggcgca 14580 gagagcctcg ttaagagcca ggaggctggg atcgaaggcc acatacgcgc gctcgaacgc 14640 ccccgccttc cagctgctgc cgggggactc ttcgcacacc gcgacgctcg ccaggacccc 14700 ggggggcgaa gttgccatgg ctgggcggga ggggcgcacg cgccagcgaa ctttacggga 14760 cacaatcccc gactgcgcgc tgcggtccca gaccctggag agtctagacg cgcgctacgt 14820 ctcgcgagac ggcgcgcatg acgcggccgt ctggttcgag gatatgaccc ccgccgagct 14880 ggaggttgtc ttcccgacta cggacgccaa gctgaactac ctgtcgcgga cgcagcggct 14940 ggcctccctc ctgacgtacg ccgggcctat aaaagcgccc gacgacgccg ccgccccgca 15000 gaccccggac accgcgtgtg tgcacggcga gctgctcgcc gccaagcggg aaagattcgc 15060 ggcggtcatt aaccggttcc tggacctgca ccagattctg cggggctgac gcgcgtgctg 15120 ttgggcggga cggttcgcga accctttggt gggtttacgc gggcacgcac gctcccatcg 15180 cgggcgccat ggcgggactg ggcaagccct acaccggcca cccaggtgac gccttcgagg 15240 gtctcgttca gcgaattcgg cttatcgtcc catctacgtt gcggggcggg gacggggagg 15300 cgggccccta ctctccctcc agcctcccct ccaggtgcgc ctttcagttt catggccatg 15360 acgggtccga cgagtcgttt cccatcgagt atgtactgcg gcttatgaac gactgggccg 15420 aggtcccgtg caacccttac ctgcgcatac agaacaccgg cgtgtcggtg ctgtttcagg 15480 ggttttttca tcgcccacac aacgcccccg ggggcgcgat tacgccagag cggaccaatg 15540 tgatcctggg ctccaccgag acgacggggc tgtccctcgg cgacctggac accatcaagg 15600 ggcggctcgg cctggatgcc cggccgatga tggccagcat gtggatcagc tgctttgtgc 15660 gcatgccccg cgtgcagctc gcgtttcggt tcatgggccc cgaagatgcc ggacggacga 15720 gacggatcct gtgccgcgcc gccgagcagg ctattacccg tcgccgccga acccggcggt 15780 cccgggaggc gtacggggcc gaggccgggc tgggggtggc cggaacgggt ttccgggcca 15840 ggggggacgg ttttggcccg ctccccttgt taacccaagg gccctcccgc ccgtggcacc 15900 aggccctgcg gggtcttaag cacctacgga ttggcccccc cgcgctcgtt ttggcggcgg 15960 gactcgtcct gggggccgct atttggtggg tggttggtgc tggcgcgcgc ctataaaaaa 16020 ggacgcaccg ccgccctaat cgccagtgcg ttccggacgc cttcgcccca cacagccctc 16080 ccgaccgaca cccccatatc gcttcccgac ctccggtccc gatggccgtc ccgcaatttc 16140 accgccccag caccgttacc accgatagcg tccgggcgct tggcatgcgc gggctcgtct 16200 tggccaccaa taactctcag tttatcatgg ataacaacca cccgcacccc cagggcaccc 16260 aaggggccgt gcgggagttt ctccgcggtc aggcggcggc gctgacggac cttggtctgg 16320 cccacgcaaa caacacgttt accccgcagc ctatgttcgc gggcgacgcc ccggccgcct 16380 ggttgcggcc cgcgtttggc ctgcggcgca cctattcacc gtttgtcgtt cgagaacctt 16440 cgacgcccgg gaccccgtga ggcccgggga gttccttctg gggtgtttta atcaataaaa 16500 gaccacacca acgcacgagc cttgcgttta atgtcgtgtt tattcaaggg agtgggatag 16560 ggttcgacgg ttcgaaactt aacacaccaa ataatcgagc gcgtctagcc cagtaacatg 16620 cgcacgtgat gtaggctggt cagcacggcg tcgctgtgat gaagcagcgc ccggcgggtc 16680 cgctgtaact gctgttgtag gcggtaacag gcgcggatca gtaccgccag ggcgctacga 16740 ccggtgcgtt gcacgtagcg tcgcgacaga actgcgtttg ccgatacggg cggggggccg 16800 aattgtaagc gcgtcacctc ttgggagtca tcggcggata acgcactgaa tggttcgttg 16860 gttatggggg agtgtggttc cccagggagt gggtcgagcg cctcggcctc ggaatccgag 16920 aggaacaacg aggtggcgtc ggagtcttcg tcgtcagaga catacagggt ctgaagcagc 16980 gacacgggcg ggggggtagc gtcgatgtgt agcgcgaggg aggatgccca cgaagacacc 17040 ccagacaagg agctgcccgt gcgtggattt gtggaagacg cggaagccgg gacggatggg 17100 cggttttgcg gtgcccggaa ccgaaccgcc ggatactccc cgggtgctac atgcccgttt 17160 tggggctggg gttggggctg gggttggggc tggggttggg gctggggttg gggctggggt 17220 tggggctggg gttggggttg gggttggggc tggggttggg gttggggctg gggctggggc 17280 tggggctggg gctggggctg gggctggggc tggggctggg gctggggctg gggctggggc 17340 tggggctggg gctggggctg gggttggggc gcggacaggc ggctgacggt caaatgcccc 17400 cgggggcgcg cagatgtggt gggcgtggcc accggctgcc gtgtagtggg gcggcgggaa 17460 accgggcctc cgggcgcaac accgccctcc agcgtcaagt atgtgggggg cgggcctgac 17520 gtcgggggcg gggcgacggg ttggaccgcg ggaggcgggg gagagggacc tgcgggagag 17580 gatgaggtcg gctcggccgg gttgcggcct aaaacagggg ccgtggggtc ggcggggtcc 17640 cagggtgaag ggagggattc ccgcgattcg gacagcgacg cgacagcggg gcgcgtaagg 17700 cgccgctgcg gcccgcctac gggaaccctg gggggggttg gcgcgggacc cgaggttagc 17760 ggggggcggc ggttttcgcc cccgggcaaa accgtgccgg ttgcgaccgg gggcggaacg 17820 ggatcgatag ggagagcggg agaagcctgg ccggcggcct ggggcccgag cgggaggggc 17880 acaccagaca ccaaagcgtg gggcgctggc tctgggggtt tgggaggggc cggggggcgc 17940 gcgaaatcgg taaccggggc gaccgtgtcg gggagggcag gcggccgcca accctgggtg 18000 gtcgcggaag cctgggtggc gcgcgccagg gagcgtgccc ggcggtgtcg gcgcgcgcgc 18060 gacccggacg aagaagcggc agaagcgcgg gaggaggcgg gggggcgggg ggcggtggca 18120 tcggggggcg ccggggaact ttggggggac ggcaagcgcc ggaagtcgtc gcgggggccc 18180 acgggcgccg gccgcgtgct ttcggccggg acgcccggtc gtgcttcgcg agccgtgact 18240 gccggcccag ggggccgcgg tgcacactgg gacgtgggga cggactgatc ggcggtgggc 18300 gaaagggggt ccggggcaag gaggggcgcg gggccgccgg agtcgtcaga cgcgagctcc 18360 tccaggccgt gaatccatgc ccacatgcga ggggggacgg gctcgccggg ggtggcgtcg 18420 gtgaatagcg tgggggccag gcttccgggc cccaacgagc cctccgcccc aacaaggtcc 18480 acagggccgg gggtcgggtt tgggaccgag gggctctggt cgtcgggggc gcgctggtac 18540 accggatgcc ccgggaatag ctcccccgac aggagggagg cgtcgaacgg ccgcccgagg 18600 atagctcgcg cgaggaaggg gtcctcgtcg gtggcgctgg cggcgaggac gtcctcgccg 18660 cccgccacaa acgggagctc ctcggtggcc tcgctgccaa caaaccgcac gtcggggggg 18720 ccgggggggt ccgggttttc ccacaacacc gcgaccgggg tcatggagat gtccacgagc 18780 accagacacg gcgggccccg ggcgaggggc cgctcggcga tgagcgcgga caggcgcggg 18840 agctgtgccg ccagacacgc gttttcgatc gggttcaggt cggcgtgcag gaggcggacg 18900 gcccacgtct cgatgtcgga cgacacggca tcgcgcaagg cggcgtccgg cccgcgagcg 18960 cgtgagtcaa acagcgtgag acacagctcc agctccgact cgcgggaaaa ggccgtggtg 19020 ttgcggagcg ccacgacgac gggcgcgccc aggagcactg ccgccagcac caggtccatg 19080 gccgtaacgc gcgccgcggg ggtgcggtgg gtggcggcgg ccggcacggc gacgtgctgg 19140 cccgtgggcc ggtagagggc gttgggggga gcggggggtg acgcctcgcg cccccccgag 19200 gggctcagcg tctgcccaga ttccagacgc gcggtcagaa gggcgtcgaa actgtcatac 19260 tctgtgtagt cgtccggaaa catgcaggtc caaagagcga ccagagcggt gcttgggaga 19320 cacatgcgcc cgaggacgct caccgccgcc agcgcctggg cgggactcag ctttcccagc 19380 gcggcgccgc gctcggttcc cagctcgggg accgagcgcc agggcgccag ggggtcggtt 19440 tcggacaact tgccgcggcg ccagtctgcc agccgcgtgc cgaacatgag gccccgggtc 19500 ggagggcctc cggccgaaaa cgctggcagc acgcggatgc gggcgtctgg atgcggggtc 19560 aggcgctgca cgaatagcat ggaatctgct gcgttctgaa acgcacgggg gagggtgaga 19620 tgcatgtact cgtgttggcg aaccagatcc aggcgccaaa aggtgtaaat gtgttccggg 19680 gagctggcca ccagcgccac cagcacgtcg ttctcgttaa aggaaacgcg gtgcctagtg 19740 gagctctggg gtccgagcgg cggccccggg gccgccgcgt caccccccca ttccagctgg 19800 gcccagcgac acccaaactc gcgcgtgaga gtggtcgcga cgagggcgac gtagagctcg 19860 gccgccgcat ccatcgaggc cccccatctc gcctggcggt ggcgcacaaa gcgtccgaag 19920 agctgaaagt tggcggcctg ggcgtcgctg agggccagct gaagccggtt gatgacggtg 19980 aggacgtaca tggccgtgac ggtcgaggcc gactccaggg tgtccgtcgg aagcgggggg 20040 cgaatgcatg ccgcctcggg acacatcagc agcgcgccga gcttgtcggt cacggccggg 20100 aagcagagcg cgtactgcag tggcgttcca tccgggacca aaaagctggg ggcgaacggc 20160 cgatccagcg tactggtggc ctcgcgcagc accaggggcc ccgggcctcc gctcactcgc 20220 aggtacgcct cgccccggcg gcgcagcatc tgcgggtcgg cctcttggcc gggtggggcg 20280 gacgcccggg cgcgggcgtc tagggcgcga agatccacga gcaggggcgc gggcgcggcc 20340 gccgcgcccg cgcccgtctg gcctgtggcc ttggcgtacg cgctatataa gcccatgcgg 20400 cgttggatga gctcccgcgc gccccggaac tcctccaccg cccatggggc caggtccccg 20460 gccaccgcgt cgaattccgc caacaggccc cccagggtgt caaagttcat ctcccaggcc 20520 acccttggca ccacctcgtc ccgcagccgg gcgctcaggt cggcgtgttg ggccacgcgc 20580 cccccgagct cctccacggc cccggcccgc tcggcgctct tggcgcccag gacgccctgg 20640 tacttggcgg gaaggcgctc gtagtcccgc tgggctcgca gccccgacac agtgttggtg 20700 gtgtcctgca gggcgcgaag ctgctcgcat gccgcgcgaa atccctcggg cgatttccag 20760 gcccccccgc gaacgcggcc gaagcgaccc catacctcgt cccactccgc ctcggcctcc 20820 tcgagagacc tccgcagggc ctcgacgcgg cgacgggtgt cgaagagcgc ctgcaggcgc 20880 gcgccctgtc gcgtcaggag gcccgggccg tcgccgctgg ccgcgcttag cgggtgcgtc 20940 tcaaaggtac gctgggcatg ttccaaccag gcgaccgcct gcacgtcgag ctcgcgcgcc 21000 ttctccgtct ggtccaccag aatttcgacc tgatccgcga tctcctccgc cgagcgcgcc 21060 tggtccagcg tcttggccac ggtcgccggg acggcgacca ccttcagcag ggtcttcaga 21120 ttggccagac cctcggcctc gagctgggcc cggcgctcgc gcgcggccag cacctcccgc 21180 agccccgccg tgacccgctc ggtggcttcg gcgcgctgct gtttggcgcg caccacggcg 21240 tccttggtat cggccaggtc ctgtcgggtc acgaatgcga cgtagtgcgc gtacgccgtg 21300 tccttcacgg ggctctggtc cacgcgctcc agcgccgcca cgcacgccac cagcgcgtcc 21360 tcgctcgggc agggcagggt gacccctgcc cggacaagct cggcggccgc cgccgggtcg 21420 ttgcgcaccg cggatatctc ctccgcggcg gcggccaggt ccagcgccac gcttccgatc 21480 gcgcgccgcg cgtcggcccg gagggcgtcc aggcgatcgc ggatatccac gtactcggcg 21540 tagccctttt gaaaaaacgg cacgtactgg cgcagggccg gcacgccccc caagtcttcc 21600 gacaggtgta ggacggcctc gtggtagtcg ataaacccgt cgttcgcctg ggcccgctcc 21660 agcagccccc ccgccagccg cagaagccgc gccaggggct cggtgtccac ccgaaacatg 21720 tcggcgtacg tgtcggccgc ggccccgaag gccgcgctcc agtcgatgcg gtgaatggct 21780 gcgagcgggg ggagcatggg gtggcgctgg ttctcggggg tgtatgggtt aaacgcaagg 21840 gccgtctcca gggcaagggt caccgccttg gcgttggttc ccagcgcctg ttcggcccgc 21900 tttcggaagt cccgggggtt gtagccgtgc gtgcccgcca gcgcctgcag gcgacggagc 21960 tcgaccacgt caaactcggc accgctttcc acgcggtcca gcacggcctc cacgtcggcg 22020 gcccagcgct cgtggctact gcgggcgcgc tgggccgcca tcttctctct gaggtcggcg 22080 gtggcggcct caagttcgtc ggcgcggcgt cgcgtggcgc cgatgacctt tcccagctcc 22140 tgcagggcgc gcccgctggg ggagtggtcc ccggccgtcc cttcggcgtg caacaggccc 22200 ccgaacctgc cctcgtggcc cgcgaggctt tcccgcgcgc cggtggtcgc gcgcgtcgcg 22260 gcctggatca gggaggcatg ctctccctcc ggttggttgg cggcccggcg cacctggacg 22320 acaaggtcgg cggcagccga ccctaaggtc gtgagctggg cgatggccac ccgcgcgtcc 22380 agggccaacc gagtcgcctt gacgtatccc gcggcgctgt cggccatggc cgctaggaag 22440 gccagggggg aggccgggtc gctggcggcc gcgcccaggg ccgtcaccgc gtcgaccagg 22500 ...

SequenceName：cos14

SequenceDescription: Custom Codon ------------ Sequence Name: cos14 Seq8: [Electronic version File name: cos28 (Seq8). WorkFile] Sequence Name: cos28 Sequence ------- <213> OrganismName: Human herpes simplex virus type 1 <400> PreSequenceString: gatcccgtta ctatcaccgt cccccccccc ccctcaaccc cggcgattgt gggtttttta 60 aaaacgacac gcgtgcgacc gtatacagaa cattgttttg gtttttattc gctatcggac 120 atggggggtg gaaactgggt ggcggggcag gcgcctccgg gggtccgccg gtgagtgtgg 180 cgcgaggggg ggtccgatga acgcaggcgc tgtctccccg gggcccgcgt aaccccgcgc 240 atatccgggg gcacgtagaa attaccttcc tcttcggact cgatatccac gacgtcaaag 300 tcgtgggcgg tcagcgagac gacctccccg tcgtcggtga tgaggacgtt gtttcggcag 360 cagcagggcc gggccccgga gaacgagagg cccatagctc ggcgagcgtg tcgtcgaatg 420 ccaggcggct gcttcgctgg atggccttat agatctccgg atcgatgcgg acgggggtaa 480 tgatcagggc gatcggaacg gcctggttcg ggagaatgga cgccttgctg ggtcctgcgg 540 ccccgagagc cccggcgccg tcctccaggc ggaacgttac gccctcctcc gcgctggtgc 600 ggtgcctgcc gataaacgtc accagatgcg ggtggggggg gcagtcgggg aagtggctgt 660 cgagcacgta gccctgcacc aagatctgct taaagttcgg gtgacggggg ttcgcgaaga 720 cgggctcgcg gcggaccaga tccccggagc tccaggacac gggggagatg gtgtggcgtc 780 cgaggtcggg ggcgccaaac agaagcacct ccgagacaac gccgctattt aactccacca 840 aggcccgatc cgcggcggag caccgccttt tttcgcccga ggcgtgggcc tctgaccagg 900 cctggtcttg cgtgacgaga gcctcctccg ggccggggac gcgcccgggc gcgaagtatc 960 gcacgctggg cttcgggatc gaccggataa atgcccggaa cgcctccggg gaccggtgtg 1020 ccatcaagtc ctcgtacgcg gaggccgtgg ggtcgctggg gtccatgggg tcgaaagcgt 1080 acttggcccg gcatttgacc tcgtaaaagg ccaggggggt cttggggact ggggccaggt 1140 agccgtgaat gtcccgagga cagacgagaa tatccaggga cgccccgacc atccccgtgt 1200 gaccgtccat gaggacccca cacgtatgca cgttctcttc ggcgaggtcg ctgggttcgt 1260 ggaagataaa gcgccgcgtg tcggcgccgg cctcgccgcc gtcgtccgcg cggcccacgc 1320 agtagcgaaa cagcaggctt cgggccgtcg gctcgttcac ccgcccgaac atcaccgccg 1380 aagactgtac atccggccgc aggctggcgt tgtgcttcag ccactggggc gagaaacacg 1440 gaccctgggg gccccagcgg agggtggatg cggtcgtgag gccccgccgg agcagggccc 1500 atagctggca gtcggcctgg ttttgcgtgg ccgcctcgta aaaccccatg aggggccggg 1560 gcgccacggc gtccgcggcg gccgggggcc cgcggcgcgt caggcgccat aggtgccgac 1620 cgagtccgcg gtccaccata cccgcctcct cgaggaccac ggccagggaa cacagataat 1680 ccaggcgggc ccagagggga ccgatggcca gaggggcgcg gacgccgcgc agcaacccgc 1740 gcaggtggcg ctcgaacgtc tcggctagta tatgggaggg cagcgcgttg gggatcaccg 1800 acgccgacca catagagtca aggtccgggg agtcgggatc ggcgtccggg tcgcgggcgt 1860 gggtgccccc aggagatagc ggaatgtctg gggtcggagg ccctgaggcg tcagaaagtg 1920 ccggcgacgc ggcccggggc ttttcgtctg cggtgtcggt ggcgtgctga tcacgtgggg 1980 ggttaacggg cgaatgggag ctcgggtcca cagctgatgt cgtctggggt ggggggggca 2040 ggggacggaa ggtggttgtc agcggaagac tgttagggcg ggggcgcttg ggggggctgt 2100 cggggccacg aggggtgtcc tcggccaggg cccagggacg cttagtcacg gtgcgtcccg 2160 gcggacatgc tgggcctacc gtggactcca tttccgagac gacgtggggg gagcggtggt 2220 tgagcgcgcc gccgggtgaa cgctgattct cacgacagcg cgtgccgcgc gcacgggttg 2280 gtgtgacaca ggcgggacac cagcaccagg agaggcttaa gctcgggagg cagcgccacc 2340 gacgacagta tcgccttgtg tgtgtgctgg taatttatac accgatccgt aaacgcgcgc 2400 cgaatcttgg gattgcggag gtggcgccgg atgccctctg ggacgtcata cgccaggccg 2460 tgggtgttgg tctcggccga gttgacaaac agggctgggt gcagcacgca gcgataggcg 2520 agcagggcca gggcgaagtc cggcgacagc tggttgttaa aatactggta accgggaaac 2580 cgggtcacgg gtacgcccag gctcggggcg acgtacacgc taaccaccaa ctccagcagc 2640 gtctggccca gggcgtacag gtcaaccgct aacccgacgt cgtgcttcag gcggtggttg 2700 gtaaattcgg cccgttcgtt gttaaggtat ttcaccaaca gctccggggg ctggttatac 2760 ccgtgaccca ccagggtgtg aaagttggct gtggttaggg cggtgggcat gccaaacatc 2820 cggggggact tgaggtccgg ctcctggagg caaaactgcc cccgggcgat cgtggagttg 2880 gagttgaggg tgacgaggct aaagtcggcg aggacggccc gccggagcga gacggcgtcc 2940 gaccgcagca tgacgaggat gttggcgcac ttgatatcca ggtggctgat cccgcaggtg 3000 gtgtttaaaa acacaacggc gcgggccagc tccgtgaagc actggtggag ggccgtcgag 3060 accgaggggt ttgttgtgcg cagggacgcc agttggccga tatacttacc gaggtccatg 3120 tcgtacgcgg ggaacactat ctgtcgttgt tgcagcgaga acccgagggg cgcgatgaag 3180 ccgcggatgt tgtgggtgcg gccggcgcgt agaacgcact ccccgaccaa cagggtcgcg 3240 atgagctcaa cggcaaacca ctccttttcc tttatggtct taacggcaag cttatgttcg 3300 cgaatcagtt ggacgtcacc gtatccccca gaccccccga agcttcgggc cccggggatc 3360 tcgagggtcg tgtagtgtag ggcggggttg atggcgaaca cggggctgca tagcttgcgg 3420 atgcgcgtga gggtgaggat gtgcgagggg gacgaggggg gtgcggttaa cgccgcctgg 3480 gatctgcgca ggggcgggcg gttcagtttg gccgccgtac cgggcgtctc gggggacgcg 3540 cggcgatgag acgagcggct cattcgccat cgggatagtc ccgcgcgaag ccgctcgcgg 3600 aggccggatc ggtggcggga cccgtgggag gagcgggaga cggcggcgtc ctggagagag 3660 gggccgctgg ggcgcccgga ggccccgtgg gggttggagt gtacgtagga tgcgagccaa 3720 tccttgaagg accgttggcg tgcaccttgg gggctgaggt tagctgccac atgaccagca 3780 ggtcgctgtc tgcgggactc atccatcctt cggccaggtc gccgtctccc cacagagaag 3840 cgttggtcgc tgcttcctcg agttgctcct cctggtccgc aagacgatcg tccacggcgt 3900 ccaggcgctc accaagcgcc ggatcgaggt accgtcggtg tgcggttaga aagtcacgac 3960 gcgccgcttg ctcctccacg cgaattttaa cacaggtcgc gcgctgtcgc atcatctcta 4020 agcgcgcgcg ggactttagc cgcgcctcca attccaagtg ggccgccttt gcagccataa 4080 aggcgccaac aaaccgagga tcttgggtgc tgacgccctc ccggtgcagc tgcagggtct 4140 ggtccttgta aatctcggct cggaggtctc tcggccaggc gtcggcgcag ggccgcgtgg 4200 gcggcatctc ggtccattcc gccaccctgc gggcgacccg gggggtgctc tgatagtctc 4260 gcgtgcccaa ggcccgtgat cggggtactt cgccgccgcg acccgccacc cggtgtgcgc 4320 gatgtttggt cagcagctgg cgtccgacgt ccagcagtac ctggagcgcc tcgagaaaca 4380 gaggcaactt aaggtgggcg cggacgaggc gtcggcgggc ctcaccatgg gcggcgatgc 4440 cctacgagtg ccctttttag atttcgcgac cgcgaccccc aagcgccacc agaccgtggt 4500 ccctggcgtc gggacgctcc acgactgctg cgagcactcg ccgctcttct cggccgtggc 4560 gcggcggctg ctgtttaata gcctggtgcc ggcgcaacta aaggggcgtg atttcggggg 4620 cgaccacacg gccaagctgg aattcctggc ccccgagttg gtacgggcgg tggcgcgact 4680 gcggtttaag gagtgcgcgc cggcggacgt ggtgcctcag cgtaacgcct actatagcgt 4740 tctgaatacg tttcaggccc tccaccgctc cgaagccttt cgccagctgg tgcactttgt 4800 gcgggacttt gcccagctgc tcaaaacctc cttccgggcc tccagcctca cggagaccac 4860 gggccccccc aaaaaacggg ccaaggtgga cgtggccacc cacggccgga cgtacggcac 4920 gctggagctg ttccaaaaaa tgatccttat gcacgccacc tactttctgg ccgccgtgct 4980 cctcggggac cacgcggagc aggtcaacac gttcctgcgt ctcgtgtttg agatccccct 5040 gtttagcgac gcggccgtgc gccacttccg ccagcgcgcc accgtgtttc tcgtcccccg 5100 gcgccacggc aagadctggt ttctggtgcc cctcatcgcg ctgtcgctgg cctcctttcg 5160 ggggatcaag atcggctaca cggcgcacat ccgcaaggcg accgagccgg tgtttgagga 5220 gatcgacgcc tgcctgcggg gctggttcgg ttcggcccga gtggaccacg ttaaagggga 5280 aaccatctcc ttctcgtttc cggacgggtc gcgcagtacc atcgtgtttg cctccagcca 5340 caacacaaac gtaagtcctc ttttctttcg catggctctc ccaaggggcc ccgggtcgac 5400 ccgacccaca cccacccacc cacatacaca cacaaccaga cgcgggagga aagtctgccc 5460 cgtgggcact gatttttatt cgggatcgct tgaggaggcc cgggcaacgg cccgggcaac 5520 ggtggggcaa ctcgtagcaa ataggcgact gatgtacgaa gagaagacac acaggcgcca 5580 cccggcgctg gtcgggggga tgttgtccgc gccgcaccgt cccccgacga cctcttgcag 5640 acggtccgtg atgcaaggac ggcggggggc ctgcagcagg gtgaccgtat ccacgggatg 5700 gccaaagaga agcggacaca ggctagcatc cccctggacc gccagggtac actgggccat 5760 cttggcccac agacacgggg cgacgcaggg acaggactcc gttacgacgg aggagagcca 5820 cagtgcgttg gcggaatcga tgtggggcgg cggggcgcag gactcgcagc cccccgggtg 5880 gttggtgatc ctggccagga gccatcccag atggcgggcc ctgcttcccg gtggacagag 5940 cgaccccagg tcgctgtcca tggcccagca gtagatctgg ccgctgggga ggtgccacca 6000 ggcccccggg cccaaggcgc agcacgcgcc cggctccggg ggggtcttcg cggggaccag 6060 atacgcgcca tccagctcgc cgaccactgg ctcctccgcg agctgttcgg tggttgggtc 6120 gggggtttcc tccggggggg tggccgcccg tatgcgtgcg aacgtgaggg tgcacaggag 6180 cggggtcagg gggtgcgtca cgctccggag gtggacgatc gcgcagtagc ggcgctcgcg 6240 gttaaagaaa aagagggcaa agaaggtgtt cgggggcaac cgcagcgcct tggggcgcgt 6300 cagatacaga aaaatctcgc agaagagggc gcgcccgggg tctgggttag gaagggccac 6360 ctgacacaga ggctcggtga ggaccgttag acaccgaaag atcttgagcc gctcgtccgc 6420 ccgaacgacg cgccacacaa agacggagtt gacaatgcgc gcgatagagt cgacgtccgt 6480 ccccaggtcg tcgactctat cgcgcgtgcc gcgagctccg gcccgggaat ccggccgggg 6540 caaggtcccc gggggaccag gcggcgccag gggccgccgg ggtcccagct gcgccatgcc 6600 gggggcgggg ggagggcaaa ccccagaggc gggggccaac ggcgcgggga ggagtgggtg 6660 ggcgaggtgg ccgggggaag gcgcccgcta gcgagaccgg ccgttcccgg acgacacctt 6720 gcgacaaaac ctaaggacag cggcccgcgc gacggggtcc gagaggctaa ggtaggccgc 6780 gatgttaatg gtgaacgcaa agccgccggg aaagacaact atgccacaga ggcggcgatt 6840 aaaccccagg cagaggtagg cgtagctttc cccgggcagg tattgctcgc agaccctgcg 6900 tggggctgtg gaggggacgg cctccatgaa gcgacattta ctctgctcgc gtttactgac 6960 gtcaccatcc atcgccacgg cgattggacg attgttaagc cgcagcgtgt ctccgcttgt 7020 gctgtagtag tcaaaaacgt aatggccgtc ggagtcggca aagcgggccg ggaggtcgtc 7080 gccgagcggg acgacccgcc gcccccgacc gccccgtccc cccaggtgtg ccaggacggc 7140 cagggcatac gcggtgtgaa aaaaggcgtc gggggcggtc ccctcgacgg cgcgcatcag 7200 gttctcgagg agaatgggga agcgcctggt cacctccccc aaccacgcgc gttggtcggg 7260 gccaaagtca tagcgcaggc gctgtgagat tcgcgggccg ccctgaagcg cggcccggat 7320 ggcctggccc agggcccgga ggcacgccag atgtatgcgc gcggtaaagg cgacctcggc 7380 ggcgatgtca aagggcggca ggacggggcg cgggtggcgc aggggcacct cgagcgcggg 7440 aaagcgtagc agcagctccg cctgcccagc gggagacagc tggtgggggc gcacgacgcg 7500 ttctgcggcg caggcctcgg tcagggccgt ggccagcgcc gaggacagca gcggagggcg 7560 ggcgcgtcgc ccgccccacg ccacggagtt ctcgtaggag acgacgacga agcgctgctt 7620 ggttccgtag tggtggcgca ggaccacgga gatagaacga cggctccaca gccagtccgg 7680 ccggtcgccg ccggccaggg cttcccatcc gcgatccaac cactcgacca gcgaccgcgg 7740 ctttgcggta ccaggggtaa gggttagaac gtcgttcagg atgtcctcgc ccccgggccc 7800 gtggggcgct ggggccacaa agcggccccc gccggggggc tccagacccg ccagcaccgc 7860 atctgcgtca gccgccccca tggcgccccc gctgacggcc tggtgaacca gggcgccctg 7920 gcgtagcccc gatgcaacgc cacaggccgc acgcccggtc cgcgctcgga ccgggtggcg 7980 gcgggtgacg tcctgcactg cccgctgaac caacgcgagg atctcctcgt tctcctgtgc 8040 gatggacacg tcctgggccg cggtcgtgtc gccgccgggg gccgtcagct gctcctccgg 8100 ggagatgggg gggtcggacg ccccgacgat gggcgggtct gcgggcgccc ccgcgtgggg 8160 ccgggccaag ggctgcggac gcggggacgc gctttccccc agacccatgg acaggtgggc 8220 cgcagcctcc ttcgcggccg gcggggcggc ggcgccaagc agagcgacgt agcggcacaa 8280 atgccgacag acgcgcatga tgcgcgtgct gtcggccgcg tagcgcgtgt tgggggggac 8340 gagctcgtcg taactaaaca gaatcacgcg ggcacagctc gcccccgagc cccacgcaag 8400 gcgcagcgcc gccacggcgt acgggtcata gacgccctgc gcgtcacaca ccacgggcag 8460 ggagacgaac aaccccccgg cgctggacgc acgcggaagg aggccagggt gtgccggcac 8520 gacgggggcc agaagctccc ccaccgcatc cgcgggcacg taggcggcaa acgccgtgca 8580 ccacggggta cagtcgccgg tggcatgagc ccgagtctgg atttcgacct ggaagtttgc 8640 ggccgtcccg agtccggggc ggccgcgcat cagggcggcc agagggattc ccgcggccgc 8700 caggcactcg ctggatatga tgacgtgaac caaagaccga gggccgaccc gggccgtggc 8760 cgagatcgtc tggacctcgt tggccaagtg cgcgttcatg gttcgggggt gggtgtgggt 8820 gtgtaggcga tgcgggtccc ccgagtccgc gggaagggcg tgggtttggc gcgcgtatgc 8880 gtattcgcca acggaggcgt gcgtgcttat gcgcggcgcg tttcttctgt ctctagggaa 8940 tccgaggcca ggactttaac ctgctctttg tcgacgaggc caactttatt cgcccggatg 9000 cggtccagac gattatgggc tttctcaacc aggccaactg caagattatc ttcgtgtcgt 9060 ccaccaacac cgggaaggcc agtacgagct ttttgtacaa cctccgcggg gccgcagacg 9120 agcttctcaa cgtggtgacc tatatatgcg atgatcacat gccgagggtg gtgacgcaca 9180 caaacgccac ggcctgttct tgttatatcc tcaacaagcc cgttttcatc acgatggacg 9240 gggcggttcg ccggaccgcc gatttgtttc tggccgattc cttcatgcag gagatcatcg 9300 ggggccaggc cagggagacc ggcgacgacc ggcccgttct gaccaagtct gcgggggagc 9360 ggtttctgtt gtaccgcccc tcgaccacca ccaacagcgg cctcatggcc cccgatttgt 9420 acgtgtacgt ggatcccgcg ttcacggcca acacccgagc ctccgggacc ggcgtcgctg 9480 tcgtcgggcg gtaccgcgac gattatatca tcttcgccct ggagcacttt tttctccgcg 9540 cgctcacggg ctcggccccc gccgacatcg cccgctgcgt cgtccacagt ctgacgcagg 9600 tcctggccct gcatcccggg gcgtttcgcg gcgtccgggt ggcggtcgag ggaaatagca 9660 gccaggactc ggccgtcgcc atcgccacgc acgtgcacac agagatgcac cgcctactgg 9720 cctcggaggg ggccgacgcg ggctcgggcc ccgagcttct cttctaccac tgcgagcctc 9780 ccgggagcgc ggtgctgtac ccctttttcc tgctcaacaa acagaagacg cccgcctttg 9840 aacactttat taaaaagttt aactccgggg gcgtcatggc ctcccaggag atcgtttccg 9900 cgacggtgcg cctgcagacc gacccggtcg agtatctgct cgagcagcta aataacctca 9960 ccgaaaccgt ctcccccaac actgacgtcc gtacgtattc cggaaaacgg aacggcgcct 10020 cggatgacct tatggtcgcc gtcattatgg ccatctacct cgcggcccag gccggacctc 10080 cgcacacatt cgctcctatc acacgcgtct cgtgagcgcc caataaacac acccaggtat 10140 gctacgcacg accacggtgt cgtctgttaa gggggggggg ggaagggggt gttggcggga 10200 agcgtgggaa cacgggggat tctctcacga ccggcaccag taccaccccc ctgtgaacac 10260 agaaacccca acccaaatcc cataaacata cgacacacag gcatattttg gaatttctta 10320 ggtttttatt tatttaggta tgctggggtt tctccctgga tgcccacccc cacccccccg 10380 tgggtctagc cgggccttag ggatagcgta taacgggggc catgtctccg gaccgcacaa 10440 cggccgcgcc gtcaaaggtg cacacccgaa ccacgggagc cagggccaag gtgtctccta 10500 gttggcccgc gtgggtcagc caggcgacga gcgcctcgta aagcggcagc cttcgctctc 10560 catcctgcat cagggccggg gcttcggggt gaatgagctg ggcggcctcc cgcgtgacac 10620 tctgcatctg cagtagagcg ttcacgtacc cgtcctgggc acttagcgca aagagccggg 10680 ggattagcgt aaggatgatg gtggttccct ccgtgatcga gtaaaccatg ttaaggacca 10740 gcgatcgcag ctcggcgttt acgggaccga gttgttggac gtccgccagc agcgagaggc 10800 gactcccgtt gtagtacagc acgttgaggt ctggcagccc tccggggttt ctggggctgg 10860 ggttcaggtc ccggatgccc ctggccacga gccgcgccac gatttcgcgc gccaggggcg 10920 atggaagcgg aacgggaaac cgcaacgtga ggtccagcga atccaggcgc acgtccgtcg 10980 cttggccctc gaacacgggc gggacgaggc tgatggggtc cccgttacag agatctacgg 11040 gggaggtgtt gcgaaggtta acggtgccgg cgtgggtgag gcccacgtcc agggggcagg 11100 cgacgattcg cgtgggaagc acccgggtga tgaccgcggg gaagcgcctt cggtacgcca 11160 gcaacaaccc caacgtgtcg ggactgacgc ctccggagac gaaggattcg tgcgccacgt 11220 cggccagcgt cagttgccgg cggatggtcg gcaggaatac cacccgccct tcgcagcgct 11280 gcagcgccgc cgcatcgggg cgcgagatgc ccgagggtat cgcgatgtca gtttcaaagc 11340 cgtccgccag catggcgccg atccacgcgg cagggagtgc agtggtggtt cgggtggcgg 11400 gaggagcgcg gtgggggtca gcggcgtagc agagacgggc gaccaacctc gcataggacg 11460 gggggtgggt cttagggggt tgggaggcga cagggacccc agagcatgcg cggggaggtc 11520 tgtcgggccc agacgcaccg agagcgaatc cgtccgcgga gtcccggctt gggttttatg 11580 gggcccggcc ctcggaatcg cggcttgtcg gcggggacaa agggggcggg gctaggggct 11640 tgcggaaaca gaagacgcgt gggataaaag aatcgcacta ccccaaggaa gggcggggcg 11700 gtttattaca gagccagtcc cttgagcggg gatgcgtcat agacgagata ctgcgcgaag 11760 tgggtctccc gcgcgtgggc ttccccgttg cgggcactgc ggaggagggc ggggtcgctg 11820 gcgcaggtga gcgggtaggc ctcctgaaac aggccacacg ggtcctccac gagttcgcgg 11880 caccccgggg ggcgcttaaa ctgtacgtcg ctggcggcgg tggccgtgga caccgccgaa 11940 cccgtctcca cgatcaggcg ctccaggcag cgatgtttgg cggcgatgtc ggccgacgta 12000 aagaacttaa agcaggggct gagcaccggc gaggccccgt tgaggtggta ggccccgtta 12060 tagagcaggt ccccgtacga aaatcgctgc gacgcccacg ggttggccgt ggccgcgaag 12120 gcccgggacg ggtcgctctg gccgtggtcg tacatgaggg cggtgacatc cccctccttg 12180 tcccccgcgt aaacgccccc ggcggcgcgt ccccgggggt tgcagggccg gcggaagtag 12240 ttgacgtcgg tcgacacggg ggtggcgata aactcacaca cggcgtcctg gccgtggtcc 12300 atccctgcgc gccgcggcac ctgggcgcac ccgaacacgg ggacgggctg ggccggcccc 12360 aggcggtttc ccgccacgac cgcgttccgc aggtacacgg ctgccgcgtt gtccaggaga 12420 gggggagccc cgcggcccag gtaaaagttt tggggaaggt tgcccatgtc ggtgacgggg 12480 ttgcggacgg ttgccgtggc cacgacggcg gtgtagccca cgcccaggtc cacgttcgcg 12540 cgcggctggg tgagcgtgaa gtttaccccc ccgccagttt cgtgccgggc cacctggagc 12600 tggcccagga agtacgcctc cgacgcgcgc tccgagaaca gcacgttctc agtcacaaag 12660 cggtcctgtc ggacgacggt gaacccaaac ccgggatgga ggcccgtctt gagctgatga 12720 tgcaaggcca cgggactgat cttgaagtac cccgccatga gcgcgtaggt cagcgcgttc 12780 tccccggccg cgctctcgcg gacgtgctgc acgacgggct gtcggatcga cgaaaagtag 12840 ttggccccca gagccggggg gaccaggggg acctgccgcg acaggtcgcg cagggccggg 12900 gggaaattgg gcgcgttcgc cacgtggtcg gccccggcga acagcgcgtg gacggggagg 12960 gggtaaaaat agtcgccatt ttggatggta tggtccagat gctggggggc catcagcagg 13020 attccggcgt gcaacgcccc gtcgaatatg cgcatgttgg tggtggacgc ggtgttggcg 13080 cccgcgtcgg gcgccgccga gcagagcagc gccgttgtgc gttcggccat gttgtgggcc 13140 agcacctgca gcgtgagcat ggcgggcccg tccactacca cgcgcccgtt gtgaaacatg 13200 gcgttgaccg tgttggccac cagattggcc gggtgcaggg ggtgcgcggg gtccgtcacg 13260 gggtcgctgg ggcactcctc gccgggggcg atctccggga ccaccatgtt ctgcagggtg 13320 gcgtatacgc ggtcgaagcg aacccccgcg gtgcagcagc ggccccgcga gaaggcgggc 13380 accatcacgt agtagtaaat cttgtggtgc acggtccagt ccgccccccg gtgcggccgg 13440 tcatccgcgg cgtccgcggc tcgggcctgg gtgttgtgca gcagctggcc gtcgttgcgg 13500 ttgaagtccg cggtcgccac gttacatgcc gccgcgtaca cggggtcgtg gccccccgcg 13560 ctaacccggc agtcgcgatg gcggtccagg gccgcgcgcc gcatcagggc gtcacagtcc 13620 cacacgaggg gtggcagcag cgccgggtct cgcattaggt gattcagctc ggcttgcgcc 13680 tgcccgccca gctccgggcc ggtcagggta aagtcatcaa ccagctgggc cagggcctcg 13740 acgtgcgcca ccaggtcccg gtacacggcc atgcactcct cgggaaggtc tcccccgagg 13800 taggtcacga cgtacgagac cagcgagtag tcgttcacga acgccgcgca ccgcgtgttg 13860 ttccagtagc tggtgatgca ctggaccacg agccgggcca gggcgcagaa gacgtgctcg 13920 ctgccgtgta tggcggcctg cagcaggtaa aacaccgccg ggtagttgcg gtcgtcgaac 13980 gccccgcgaa cggcggcgat ggtggcgggg gccatggcgt ggcgtcccac ccccagctcc 14040 aggccccggg cgtcccggaa cgccgccgga catagcgcca ggggcaagtt gccgttcacc 14100 acgcgccagg tggcctggat ctcccccggg ccggccgggg gaacgtcccc ccccggcagc 14160 tccacgtcgg ccacccccac aaagaagtcg aacgcggggt gcagctcaag agccaggttg 14220 gcgttgtcgg gctgcataaa ctgctccggg gtcatctggc cttccgcgac ccatcggacc 14280 cgcccgtggg ccaggcgctg cccccaggcg ttcaaaaaca gctgctgcat gtctgcggcg 14340 gggccggccg gggccgccac gtacgccccg tacggattgg cggcttcgac ggggtcgcgg 14400 ttaaggcccc cgaccgccgc gtcaacgttc atcagcgaag ggtggcacac ggtcccgatc 14460 gcgtgttcca gagacaggcg cagcacctgg cggtccttcc cccaaaaaaa cagctggcgg 14520 ggcgggaagg cgcggggatc cgggtggccg ggggcgggga ctaggtcccc ggcgtgcgcg 14580 gcaaaccgtt ccatgaccgg attgaacagg cccaggggca ggacgaacgt caggtccatg 14640 gcgcccacca gggggtaggg aacgttggtg gcggcgtaga tgcgcttctc cagggcctcc 14700 agaaagacca gcttctcgcc gatggacacc agatccgcgc gcacgcgcgt cgtctggggg 14760 gcgctctcga gctcgtccag cgtctgccgg ttcaggtcga gctgctcctc ctgcatctcc 14820 agcaggtggc ggcccacgtc gtccagactt cgcacggcct tgcccatcac gagcgccgtg 14880 accaggttgg ccccgttcag gaccatctcg ccgtacgtca ccggcacgtc ggcttcggtg 14940 tcctccactt tcaggaagga ctgcaggagg cgctgtttga tcggggcggt ggtgacgagc 15000 accccgtcga ccggccgccc gcgcgtgtcg gcatgcgtca gacggggcac ggccacggag 15060 ggctgcgtgg ccgtggtgag gtccacgagc caggcctcga cggcctcccg gcggtggccc 15120 gccttgccca ggaaaaagct cgtctcgcag aagcttcgct ttagctcggc gaccagggtc 15180 gcccgggcca ccctggtggc caggcggccg ttgtccaggt atcgttgcat cggcaacaac 15240 aaagccaggg gcggcgcctt ttccagcagc acgtgcagca tctggtcggc cgtgccgcgc 15300 tcaaacgccc cgaggacggc ctggacgttg cgagcgagct gttggatggc gcgcaactgg 15360 cgatgcgcgc cgatacccgt cccgtccagg gcctcccccg tgagcagggc gatggcctcg 15420 gtggccaggc tgaaggcggc gttcagggcc cggcggtcga taatcttggt catgtaattg 15480 tgtgtgggtt gctcgatggg gtgcgggccg tcgcgggcaa tcagcggctg gtggacctcg 15540 aactgtacgc gcccctcgtt catgtaggcc agctccggaa acttggtaca cacgcacgcc 15600 accgacaacc cgagctccag aaagcgcacg agcgacaggg tgttgcaata cgaccccagc 15660 agggcgtcga actcgacgtc gtacaggctg tttgcatcgg agcgcacgcg ggaaaaaaaa 15720 tcaaacaggc gtcgatgcga cgccacctcg atcgtgctaa ggagggaccc ggtcggcacc 15780 atggccgcgg cataccggta tcccggaggg tcgcggttgg gagcggccat ggggtcgcgt 15840 ggagatcggc tgtctctagc gatattggcc cggggaggct aagatccacc ccaacgcccg 15900 gccacccgtg tacgtgcccg acggcccaag gtccaccgaa agacacgacg ggcccggacc 15960 caaaaaggcg ggggatgctg tgtgagaggc cgggtgccgg tcggggggga aaggcaccgg 16020 gagaaggctg cggcctcgtt ccaggagaac ccagtgtccc caacagaccc ggggacgtgg 16080 gatcccaggc cttatatacc cccccccccg ccccaccccc gttagaacgc gacgggtgca 16140 ttcaagatgg ccctggtcca aaagcgtgcc aggaagaaat tggcagaggc ggcaaagctg 16200 tccgccgccg ccacccacat cgaggccccg gccgcgcagg ctatccccag ggcccgtgtg 16260 cgcaggggat cggtgggcgg cagcatttgg ttggtggcga taaagtggaa aagcccgtcc 16320 ggactgaagg tctcgtgggc ggcggcgaac aaggcacaca gggccgtgcc tcccaaaaac 16380 acggacatcc cccaaaacac gggcgccgac aacggcagac gatccctctt gatgttaacg 16440 tacaggagga gcgcccgcac cgcccacgta acgtagtagc cgacgatggc ggccaggata 16500 caggccggcg ccaccaccct tccggtcagc ccgtaataca tgcccgctgc caccatctcc 16560 aacggcttca ggaccaaaaa cgaccaaagg aacagaatca cgcgctttga aaagaccggc 16620 tgggtatggg gcggaagacg cgagtatgcc gaactgacaa aaaaatcaga ggtgccgtac 16680 gaggacaatg aaaactgttc ctccagcggc agttctccct cctccccccc gaaggcggcc 16740 tcgtcgacca gatctcgatc caccagagga aggtcatccc gcatggtcat ggggtgtgcg 16800 gtggaggtgg ggagaccgaa accgcaaagg gtcgcttacg tcagcaggat cccgagatca 16860 aagacacccg ggttcttgca caaacaccac ccgggttgca tccgcggagg cgagtgtttt 16920 gataaggccg ttccgcgcct tgatataacc tttgatgttg accacaaaac ccggaattta 16980 cgcctacgcc ccaatgccca cgcaagatga ggtaggtaac ccccccgtgg gtgtgacgtt 17040 gcgtttagtt cattggaggc caaggggaaa aatggggtgg ggaggaaacg gaaaacccag 17100 taggccgtgt cgggaacacg cccggggttg tcctcaaaag gcagggtcca tactacggaa 17160 gccgtcgttg tattcgagac ctgcctgtgc aacgcacgtc ggggttgcct gtgtccggtt 17220 cggcccccac cgcgtgcggc acgcacgagg acgagtccgc gtgctttatt ggcgttccaa 17280 gcgttgccct ccagtttctg ttgtcggtgt tcccccatac ccacgcccac atccaccgta 17340 gggggcctct gggccgtgtt acgtcgccgc ccgcgatgga gcttagctac gccaccacca 17400 tgcactaccg ggacgttgtg ttttacgtca caacggaccg aaaccgggcc tactttgtgt 17460 gcggggggtg tgtttattcc gtggggcggc cgtgtgcctc gcagcccggg gagattgcca 17520 agtttggtct ggtcgttcga gggacaggcc cagacgaccg cgtggtcgcc aactatgtac 17580 gaagcgagct ccgacaacgc ggcctgcagg acgtgcgtcc cattggggag gacgaggtgt 17640 ttctggacag cgtgtgtctt ctaaacccga acgtgagctc cgagctggat gtgattaaca 17700 cgaacgacgt ggaagtgctg gacgaatgtc tggccgagta ctgcacctcg ctgcgaacca 17760 gcccgggtgt gctaatatcc gggctgcgcg tgcgggcgca ggacagaatc atcgagttgt 17820 ttgaacaccc aacgatagtc aacgtttcct cgcactttgt gtataccccg tccccatacg 17880 tgttcgccct ggcccaggcg cacctccccc ggctcccgag ctcgctggag gccctggtga 17940 gcggcctgtt tgacggcatc cccgccccac gccagccact tgacgcccac aacccgcgca 18000 cggatgtggt tatcacgggc cgccgcgccc cacgacccat cgccgggtcg ggggcggggt 18060 cggggggcgc gggcgccaag cgggccaccg tcagcgagtt cgtgcaagtc aaacacattg 18120 accgcgtggg ccccgctggc gtttcgccgg cgcctccgcc aaacaacacc gactcgagtt 18180 ccctggtgcc cggggcccag gattccgccc cgcccggccc cacgctaagg gagctgtggt 18240 gggtgtttta tgccgcagac cgggcgctgg aggagccccg cgccgactct ggcctcaccc 18300 gcgaggaggt acgtgccgta cgtgggttcc gggagcaggc gtggaaactg tttggctccg 18360 cgggggcccc gcgggcgttt atcggggccg cgttgggcct gagccccctc caaaagctag 18420 ccgtttacta ctatatcatc caccgagaga ggcgcctgtc ccccttcccc gcgctagtcc 18480 ggctcgtagg ccggtacaca cagcgccacg gcctgtacgt ccctcggccc gacgacccag 18540 tcttggccga tgccatcaac gggctgtttc gcgacgcgct ggcggccgga accacagccg 18600 agcagctcct catgttcgac cttctccccc caaaggacgt gccggtggga agcgacgtgc 18660 aggccgacag caccgctctg ctgcgcttta tagaatcgca acgtctcgcc gtccccgggg 18720 gggtgatctc ccccgagcac gtcgcgtacc ttggtgcgtt cctgagcgtg ctgtacgctg 18780 gccgcgggcg catgtccgca gccacgcaca ccgcgcggct gacaggggtg acctccctgg 18840 tgctagcggt gggtgacgtg gaccgtcttt ccgcgtttga ccgcggagcg gcgggcgcgg 18900 ccagccgcac gcgggccgcc gggtacctgg atgtgcttct taccgttcgt ctcgctcgct 18960 cccaacacgg acagtctgtg taaaagaccc caataaacgt atatcgctac tacacccttg 19020 tgtgtcaatg gacgcctctc cggggggggg ggagggaaag caaagagggg ctgggggagc 19080 ggcaccaccg gggcctgaac aaacaaacca cagacacggt tacagtttat tcggtcgggc 19140 ggagaaacgg ccgaagccac gcccacttta ttcgcgtctc caaaaaaacg ggacacttgt 19200 ccggagaacc tttaggatgc cagccagggc ggcggtaatc ataaccacgc ccagcgcaga 19260 ggcggccaga aacccgggcg caattgcggc cacgggctgc gtgtcaaagg ctagcaaatg 19320 aatgacggtt ccgtttggaa atagcaacaa ggccgtggac ggcacgtcgc tcgaaaacac 19380 gcttggggcg ccctccgtcg gcccggcggc gatttgctgc tgtgtgttgt ccgtatccac 19440 cagcaacaca gacatgacct ccccggccgg ggtgtagcgc ataaacacgg cccccacgag 19500 ccccaggtcg cgctggtttt gggtgcgcac cagccgcttg gactcgatat cccgggtgga 19560 gccttcgcat gtcgcggtga ggtaggttag gaacagtggg cgtcggacgt cgacgccggt 19620 gagcttgtag ccgatccccc ggggcagagg ggagtgggtg acgacgtagc tggcgttgtg 19680 ggtgatgggt accaggatcc gtggctcgac gttggcagac tgccccccgc accgatgtga 19740 ggcctcaggg acgaaggcgc ggatcagggc gttgtagtgt gcccaacgcg tcagggtcga 19800 ggcgaggccg tgggtctgct gggccaggac ttcgaccggg gtctcggatc gggtggcttg 19860 agccagcgcg tccaggataa acacgctctc gtctagatca aagcgcaggg aggccgcgca 19920 tggcgaaaag tggtccggaa gccaaaagag ggttttctgg tggtcggccc gggccagcgc 19980 ggtccggagg tcggcgttgg tcgctgcggc gacgtcggac gtacacaggg ccgaggctat 20040 cagaaggctc cggcgggcgc gttcccgctg caccgccgag gggacgccag ccaagaacgg 20100 ctgccggagg acagccgagg cgtaaaatag cgcccggtgg acgaccgggg tggtcagcac 20160 gcggccccct agaaactcgg catacagggc gtcgatgaga tgggctgcgc tgggcgccac 20220 tgcgtcgtac gccgaggggc tatccagcac gaaggccagc tgatagccca gcgcgtgtaa 20280 tgccaagctc tgttcgcgct ccagaatctc ggccaccagg tgctggagcc gagcctctag 20340 ctgcaggcgg gccgtgggat ccaagactga cacattaaaa aacacagaat ccgcggcaca 20400 gcccgcggcc ccgcgggcgg ccaacccggc aagcgcgcgc gagtgggcca aaaagcctag 20460 caggtcggag aggcagaccg cgccgtttgc gtgggcggcg ttcacgaaag caaaacccga 20520 cgtcgcgagc agccccgtta ggcgccagaa gagagggggg cgcgggccct gctcggcgcc 20580 cgcgtccccc gagaaaaact ccgcgtatgc ccgcgacagg aactgggcgt agttcgtgcc 20640 ctcctccggg tagccgccca cgcggcggag ggcgtccagc gcggagccgt tgtcggcccg 20700 cgtcagggac cctaggacaa agacccgata ccgggggccg cccgggggcc cgggaagagc 20760 ccccgggggg ttttcgtccg cggggtcccc gacccgatct agcgtctggc ccgcggggac 20820 caccatcact tccaccggag ggctgtcgtg catggatatc acgagcccca tgaattcccg 20880 cccgtagcgc gcgcgcacca gcgcggcatc gcacccgagc accagctccc ccgtcgtcca 20940 gatgcccacg ggccacgtcg aggccgacgg ggagaaatac acgtacctac ctggggatct 21000 caacaggccc cgggtggcca accaggtcgt ggacgcgttg tgcaggtgcg tgatgtccag 21060 ctccgtcgtc gggtgccgcc gggccccaac cggcggtcgg gggggcggtg tatcacgcgg 21120 cccgctcggg tggctcgccg tcgccacgtt gtctccccgc gggaacgtca gggcctcggg 21180 gtcagggacg gccgaaaacg ttacccaggc ccgggaacgc agcaacacgg aggcggctgg 21240 attgtgcaag agacccttaa ggggggcgac cgagggggga ggctgggcgg tcggctcgac 21300 cgtggtgggg gcgggcaggc tcgcgttcgg gggccggccg agcaggtagg tcttcgggat 21360 gtaaagcagc tggccggggt cccgcggaaa ctcggccgtg gtgaccaata caaaacaaaa 21420 gcgctcctcg taccagcgaa gaaggggcag agatgccgta gtcaggttta gttcgtccgg 21480 cggcgccaga aatccgcgcg gtggtttttg ggggtcgggg gtgtttggca gccacagacg 21540 cccggtgttc gtgtcgcgcc agtacatgcg gtccatgccc aggccatcca aaaaccatgg 21600 gtctgtctgc tcagtccagt cgtggacctg accccacgca acgcccaaaa taataacccc 21660 cacgaaccat aaaccattcc ccatggggga ccccgtccct aacccacggg gcccgtggct 21720 atggcagggc ttgccgcccc gacgttggct gcgagccctg ggccttcacc cgaacttggg 21780 ggttggggtg gggaaaagga agaaacgcgg gcgtattggt cccaatgggg tctcggtggg 21840 gtatcgacag agtgccagcc ctgggaccga accccgcgtt tatgaacaaa cgacccaaca 21900 cccgtgcgtt ttattctgtc tttttattgc cgtcatagcg cgggttcctt ccggtattgt 21960 ctccttccgt gtttcagtta gcctccccca tctcccgggc aaacgtgcgc gccaggtcgc 22020 agatcgtcgg tatggagcct ggggtggtga cgtgggtctg gaccatcccg gaggtaagtt 22080 gcagcagggc gtcccggcag ccggcgggcg attggtcgta atccaggata aagacatgca 22140 tgggacggag gcgtttggcc aagacgtcca aagcccaggc aaacacgtta tacaggtcgc 22200 cgttgggggc cagcaactcg ggggcccgaa acagggtaaa taacgtgtcc ccgatatggg 22260 gtcgtgggcc cgcgttgctc tggggctcgg caccctgggg cggcacggcc gcccccgaaa 22320 gctgtcccca atcctcccgc cacgacccgc cgccctgcag ataccgcacc gtattggcaa 22380 gcagcccata aacgcggcga atcgcggcca gcatagccag gtcaagccgc tcgccggggc 22440 gctggcgttt ggccaggcgg tcgatgtgtc tgtcctccgg aagggccccc aacacgatgt 22500 ttgtgccggg caaggtcggc gggatgaggg ccacgaacgc cagcacggcc tggggggtca 22560 tgctgcccat aaggtatcgc gcggccgggt agcacaggag ggcggcgatg ggatggcggt 22620 cgaagatgag ggtgagggcc gggggcgggg catgtgagct cccagcctcc cccccgatat 22680 gaggagccag aacggcgtcg gtcacggcat aaggcatgcc cattgttatc tgggcgcttg 22740 tcattaccac cgccgcgtcc ccggccgata tctcaccctg gtcgaggcgg tgttgtgtgg 22800 tgtagatgtt cgcgattgtc tcggaagccc ccaacacccg ccagtaagtc atcggctcgg 22860 gtacgtagac gatatcgtcg cgcgaaccca gggccaccag cagttgcgtg gtggtggttt 22920 tccccatccc gtggggaccg tctatataaa cccgcagtag cgtgggcatt ttctgctcca 22980 ggcggacttc cgtggctttt tgttgccggc gagggcgcaa cgccgtacgt cggttgttat 23040 ggccgcgaga acgcgcagcc tggtcgaacg cagacgcgtg ttgatggcag gggtacgaag 23100 ccatacgcgc ttctacaagg cgctggccga agaggtgcgg gagtttcacg ccaccaagat 23160 ctgcggcacg ctgttgacgc tgttaagcgg gtcgctgcag ggtcgctcgg tattcgaggc 23220 cacacgcgtc accttaatat gcgaagtgga cctgggaccg cgccgccccg actgcatctg 23280 cgtgttcgaa ttcgccaatg acaagacgct gggcggggtt tgtgtcatca tagaactaaa 23340 gacatgcaaa tatatttctt ccggggacac cgccagcaaa cgcgagcaac gggccacggg 23400 gatgaagcag ctgcgccact ccctgaagct cctgcagtcc ctcgcgcctc cgggtgacaa 23460 gatagtgtac ctgtgccccg tcctggtgtt tgtcgcccaa cggacgctcc gcgtcagccg 23520 cgtgacccgg ctcgtcccgc agaaggtctc cggtaatatc accgcagtcg tgcggatgct 23580 ccagagcctg tccacgtata cggtccccat tgagcctagg acccagcgag cccgtcgccg 23640 ccgcggcggc gccgcccggg ggtctgcgag cagaccgaaa aggtcacact ctggggcgcg 23700 cgacccgccc gagtcagcgg cccgccagtt accacccgcc gaccaaaccc ccacctccac 23760 ggagggcggg ggggtgctta agaggatcgc ggcgctcttc tgcgtgcccg tggccaccaa 23820 gaccaaaccc cgagccgcct ccgaatgaga gtgtttcgtt ccttccccct ccccccgcgt 23880 cagacaaacc ctaaccaccg cttaagcggc ccccgcgagg tccgaagact catttggatc 23940 cggcgggagc cacccgacaa cagcccccgg gttttcccac gccagacgcc ggtccgctgt 24000 gccatcgcgc cccctcatcc caccccccat cttgtcccca aataaaacaa ggtctggtag 24060 ttaggacaac gaccgcagtt ctcgtgtgtt attttcgctc tccgcctctc gcagatggac 24120 ccgtactgcc catttgacgc tctggacgtc tgggaacaca ggcgcttcat agtcgccgat 24180 tcccgaaact tcatcacccc cgagttcccc cgggactttt ggatgtcgcc cgtctttaac 24240 ctcccccggg agacggcggc ggagcaggtg gtcgtcctac aggcccagcg cacagcggct 24300 gccgctgccc tggagaacgc cgccatgcag gcggccgagc tccccgtcga tatcgagcgc 24360 cggttacgcc cgatcgaacg gaacgtgcac gagatcgcag gcgccctgga ggcgctggag 24420 acggcggcgg ccgccgccga agaggcggat gccgcgcgcg gggatgagcc ggcgggtggg 24480 ggcgacgggg gggcgccccc gggtctggcc gtcgcggaga tggaggtcca gatcgtgcgc 24540 aacgacccgc cgctacgata cgacaccaac ctccccgtgg atctgctaca catggtgtac 24600 gcgggccgcg gggcgaccgg ctcgtcgggg gtggtgttcg ggacctggta ccgcactatc 24660 caggaccgca ccatcacgga ctttcccctg accacccgca gtgccgactt tcgggacggc 24720 cgtatgtcca agaccttcat gacggcgctg gtactgtccc tgcaggcgtg cggccggctg 24780 tatgtgggcc agcgccacta ttccgccttc gagtgcgccg tgttgtgtct ctacctgctg 24840 taccgaaaca cgcacggggc cgccgacgat agcgaccgcg ctccggtcac gttcggggat 24900 ctgctgggcc ggctgccccg ctacctggcg tgcctggccg cggtgatcgg gaccgagggc 24960 ggccggccac agtaccgcta ccgcgacgac aagctcccca agacgcagtt cgcggccggc 25020 gggggccgct acgaacacgg agcgctggcg tcgcacatcg tgatcgccac gctgatgcac 25080 cacggggtgc tcccggcggc cccgggggac gtcccccggg acgcgagtac ccacgttaac 25140 cccgacggcg tggcgcacca cgacgacata aaccgcgccg ccgccgcgtt cctcagccgg 25200 ggccacaacc tattcctgtg ggaggaccag actctgctgc gggcaaccgc gaacaccata 25260 acggccctgg gcgttatcca gcggctcctc gcgaacggca acgtgtacgc ggaccgcctc 25320 aacaaccgcc tgcagctggg catgctgatc cccggagccg tcccttcgga ggccatcgcc 25380 cgtggggcct ccgggtccga ctcgggggcc atcaagagcg gagacaacaa tctggaggcg 25440 ctatgtgcca attacgtgct tccgctgtac cgggccgacc cggcggtcga gctgacccag 25500 ctgtttcccg gcctggccgc cctgtgtctt gacgcccagg cggggcggcc ggtcgggtcg 25560 acgcggcggg tggtggatat gtcatcgggg gcccgccagg cggcgctggt gcgcctcacc 25620 gccctggaac tcatcaaccg cacccgcaca aaccccaccc ctgtggggga ggttatccac 25680 gcccacgacg ccctggcgat ccaatacgaa caggggcttg gcctgctggc gcagcaggca 25740 cgcattggct tgggctccaa caccaagcgt ttctccgcgt tcaacgttag cagcgactac 25800 gacatgttgt actttttatg tctggggttc attccacagt acctgtcggc ggtttagtgg 25860 gtggtgggcg aggggggagg gggcattagg gagaaaaaac aagagcctcc gttgggtttt 25920 ctttgtgcct gtactcaaaa ggtcataccc cgtaaacggc gggctccagt cccggcccgg 25980 cggttggcgt gaacgcaacg gcgggagctg ggttagcgtt tagtttagca ttcgctctcg 26040 cctttccgcc cgccccccga ccgttgcgcc tttttttttt tcgtccacca aagtctctgt 26100 gggtgcgcgc atggcagccg atgccccggg agaccggatg gaggagcccc tgcccgacag 26160 ggccgtgccc atttacgtgg ctgggttttt ggccctgtat gacagcgggg actcgggcga 26220 gttggcattg gatccggata cggtgcgggc ggccctgcct ccggataacc cactcccgat 26280 taacgtggac caccgcgctg gctgcgaggt ggggcgggtg ctggccgtgg tcgacgaccc 26340 ccgcgggccg ttttttgtgg ggctgatcgc ctgcgtgcag ctggagcgcg tcctcgagac 26400 ggccgccagc gctgcgattt tcgagcgccg cgggccgccg ctctcccggg aggagcgcct 26460 gttgtacctg atcaccaact acctgccctc ggtctccctg gccacaaaac gcctgggggg 26520 cgaggcgcac cccgatcgca cgctgttcgc gcacgtcgcg ctgtgcgcga tcgggcggcg 26580 cctcggcact atcgtcacct acgacaccgg tctcgacgcc gccatcgcgc cctttcgcca 26640 cctgtcgccg gcgtctcgcg agggggcgcg gcgactggcc gccgaggccg agctcgcgct 26700 gtccgggcgc acctgggcgc ccggcgtgga ggcgctgacc cacacgctgc tttccaccgc 26760 cgttaacaac atgatgctgc gggaccgctg gagcctggtg gccgagcggc ggcggcaggc 26820 cgggatcgcc ggacacacct acctccaggc gagcgaaaaa ttcaaaatgt ggggggcgga 26880 gcctgtttcc gcgccggcgc gcgggtataa gaacggggcc ccggagtcca cggacatacc 26940 gcccggctcg atcgctgccg cgccgcaggg tgaccggtgc ccaatcgtcc gtcagcgcgg 27000 ggtcgccttg tccccggtac tgccccccat gaaccccgtt ccgacatcgg gcaccccggc 27060 ccccgcgccg cccggcgacg ggagctacct gtggatcccg gcctcccatt acaaccagct 27120 cgtcgccggc catgccgcgc cccaacccca gccgcattcc gcgtttggtt tcccggctgc 27180 ggcggggtcc gtggcctatg ggcctcacgg tgcgggtctt tcccagcatt accctcccca 27240 cgtcgcccat cagtatcccg gggtgctgtt ctcgggaccc agcccactcg aggcgcagat 27300 agccgcgttg gtgggggcca tagccgcgga ccgccaggcg ggcggtcagc cggccgcggg 27360 agaccctggg gtccgggggt cgggaaagcg tcgccggtac gaggcggggc cgtcggagtc 27420 ctactgcgac caggacgaac cggacgcgga ctacccgtac taccccgggg aggctcgagg 27480 cgcgccgcgc ggggtcgact cccggcgcgc ggcccgccat tctcccggga ccaacgagac 27540 catcacggcg ctgatggggg cggtgacgtc tctgcagcag gaactggcgc acatgcgggc 27600 tcggaccagc gccccctatg gaatgtacac gccggtggcg cactatcgcc ctcaggtggg 27660 ggagccggaa ccaacaacga cccacccggc cctttgtccc ccggaggccg tgtatcgccc 27720 cccaccacac agcgccccct acggtcctcc ccagggtccg gcgtcccatg cccccactcc 27780 cccgtatgcc ccagctgcct gcccgccagg cccgccaccg cccccatgtc cttccaccca 27840 gacgcgcgcc cctctaccga cggagcccgc gttccccccc gccgccaccg gatcccaacc 27900 ggaggcatcc aacgcggagg ccggggccct tgtcaacgcc agcagcgcag cacacgtgga 27960 cgttgacacg gcccgcgccg ccgatttgtt cgtctctcag atgatggggg cccgctgatt 28020 cgccccggtc tttggtacca tgggatgtct tactgtatat ctttttaaat aaaccaggta 28080 ataccaaata agacccattg gtgtatgttc tttttttatt gggaggcgcg ggtaggcggg 28140 tagctttaca atgcaaaagc cttcgacgtg gaggaaggcg tggggggggg gggaatcggc 28200 actgaccaag ggggtccgtt ttgtcacggg aaaggaaaga ggaaacaggc cgcggacacc 28260 cgggggagtt tgtgttccct tttctttctt cccacacaca caaaaggcgt accaaacaaa 28320 caaaccaaaa gatgcacatg cggtttaaca cccgtggttt ttatttacaa caaacccccc 28380 atcacaggtc gtcctcgtcg gcgtcaccgt ctttgttggg aacttgggtg tagttggtgt 28440 tgcggcgctt gcgcatgacc atgtcggtga ccttggcgct gagcagcgcg ctcgtgccct 28500 tcttcttggc cttgtgttcc gtgcgctcca tggcagacac cagggccatg taccgtatca 28560 tctcccgggc ctcggctagc ttggcctcgt caaagtcgcc gccctcctcg ccctccccgg 28620 acgcgtccgg gttggtgggg ttcttgagct ccttggtggt tagcgggtac agggccttca 28680 tggggttgct ctgcagccgc atgacgtagc gaaaggcgaa gaaggccgcc gccaggccgg 28740 ccaggaccaa cagacccacg gccagcgccc caaaggggtt ggacatgaag gaggacacgc 28800 ccgacacggc cgataccacg ccgcccacga tgcccatcac caccttgccg accgcgcgcc 28860 ccaggtcgcc catcccctcg aagaacgcgc ccaggcccgc aaacatggcg gcgttggcgt 28920 cggcgtggat gaccgtgtcg atgtcggcga agcgcaggtc gtgcagctgg ttgcggcgct 28980 ggacctccgt gtagtccagc aggccgctgt ccttgatctc gtggcgggtg tacacctcca 29040 gggggacaaa ctcgtgatcc tccagcatgg tgatgttgag gtcgatgaag gtgctgacgg 29100 tggtgatgtc ggcgcggctc agctggtggg agtacgcgta ctcctcgaag tacacgtagc 29160 ccccaccgaa ggtgaagtag cgccggtgtc ccacggtgca cggctcgatc gcatcgcgcg 29220 tcagccgcag ctcgttgttc tcccccagct gcccctcgac caacgggccc tggtcttcgt 29280 accgaaagct gaccaggggg cggctgtagc aggccccggg ccgcgagctg atgcgcatcg 29340 agttttggac gatcacgttg tccgcggcga ccggcacgca cgtggagacg gccatcacgt 29400 cgccgagcat ccgcgcgctc acccgccggc ccacggtggc cgaggcgatg gcgttggggt 29460 tcagcttgcg ggcctcgttc cacagggtca gctcgtgatt ctgcagctcg caccacgcga 29520 tggcaacgcg gcccaacata tcgttgacat ggcgctgtat gtggttgtac gtaaactgca 29580 gcctggcgaa ctcgatggag gaggtggtct tgatgcgctc cacggacgcg ttggcgctgg 29640 ccccgggcgg cgggggcgtg gggtttgggg gcttgcggct ctgctcgcgg aggtgttccc 29700 gcacgtacag ctccgcgagc gtgttgctga gaaggggctg gtacgcgatc agaaagcccc 29760 cattggccag gtagtactgc ggctggccca ccttgatgtg cgtcgcgttg tacctgcggg 29820 cgaagatgcg gtccatggcg tcgcgggcgt ccttgccgat gcagtccccc aggtccacgc 29880 gcgagagcgg gtactcggtc aggttggtgg tgaaggtggt ggatatggcg tcggaagaga 29940 atcggaagga gccgccgtac tcggagcgca gcatctcgtc cacctcctgc cacttggtca 30000 tggtgcagac cgacgggcgc tttggcaccc agtcccaggc cacggtgaac ttgggggtcg 30060 tgagcaggtt ccgggtggtc ggcgccgtgg cccgggcctt ggtggtgagg tcgcgcgcgt 30120 agaagccgtc gacctgcttg aagcggtcgg cggcgtagct ggtgtgttcg gtgtgcgacc 30180 cctcccggta gccgtaaaac ggggacatgt acacaaagtc gccagtcgcc aacacaaact 30240 cgtcgtacgg gtacaccgag cgcgcgtcca cctcctcgac gatgcagttt accgtcgtcc 30300 cgtaccggtg gaacgcctcc acccgcgagg ggttgtactt gaggtcggtg gtgtgccagc 30360 cccggctcgt gcgggtcgcg gcgttggccg gtttcagctc catgtcggtc tcgtggtcgt 30420 cccggtgaaa cgcggtggtc tccaggttgt tgcgcacgta cttggccgtg gaccgacaga 30480 cccccttggc gttgatcttg tcgatcacct cctcgaaggg gacgggggcg cggtcctcaa 30540 agatccccat aaactgggag tagcggtggc cgaaccacac ctgcgaaacg gtgacgtctt 30600 tgtagtacat ggtggccttg aacttgtacg gggcgatgtt ctccttgaag accaccgcga 30660 tgccctccgt gtagttctga ccctcgggcc gggtcgggca gcggcgcggc tgctcgaact 30720 gcaccaccgt ggcgcccgtg gggggtgggc acacgtaaaa gtttgcatcg gtgttctccg 30780 ccttgatgtc ccgcaggtgc tcgcgcaggg tggcgtggcc cgcggcgacg gtcgcgttgt 30840 cgccggcggg gcgcggcggc tttgggggtt tcggttttct gttcttcttc ggtttcgggt 30900 cccccgttgg gggggcgcca ggggcgggcg gcgccggagt ggcagggccc ccgttcgccg 30960 cctgggtcgc ggccgcgacc ccaggcgtgc cgggggaact cggagccgcc gacgccacca 31020 ggacccccag cgtcaacccc aagagcgccc atacgacgaa ccaccggcgc ccccgcgcgg 31080 gggcgccctg gcgcatggcg ggactacggg ggcccgtcgt gccccccgtc aggtagcctg 31140 ggggcgaggt gctggaggac cgagtagagg atcgagaaaa cgtctcggtc gtagaccacg 31200 accgaccggg ggccgataca gccgtcgggg gcgctctcga cgatggccac cagcggacag 31260 tcggagtcgt acgtgagata tacgccgggc gggtaacggt aacgaccttc ggaggtcggg 31320 cggctgcagt ccgggcggcg caactcgagc tccccgcacc ggtagaccga ggcaaagagt 31380 gtggtggcga taatcagctc gcgaatatat cgccaggcgg cgcgctgagt gggcgttatt 31440 ccggaaatgc cgtcaaaaca gtaaaacctc tgaaattcgc tgacggccca atcagcaccc 31500 gagccccccg cccccatgat gaaccgggcg agctcctcct tcaggtgcgg caggagcccc 31560 acgttctcga cgctgtaata cagcgcggtg ttggggggct gggcgaagct gtgggtggag 31620 tgatcaaaga ggggcccgtt gacgagctcg aagaagcgat gggtgatgct ggggagcagg 31680 gccgggtcca cctggtgtcg caggagagac gctcgcatga accggtgcgc gtcgaacacg 31740 cccggcgccg agcggttgtc gatgaccgtg cccgcgcccg ccgtcagggc gcagaagcgc 31800 gcgcgcgccg caaagccgtt ggcgaccgcg gcgaacgtcg cgggcagcac ctcgccgtgg 31860 acgctgaccc gcagcatctt ctcgagctcc ccgcgctgct cgcggacgca gcgccccagg 31920 ctggccaacg accgcttcgt caggcggtcc gcgtacagcc gccgtcgctc ccgcacgtcc 31980 gcggccgctt gcgtggcgat gtccccccac gtctcgggcc cctgcccccc gggcccgcgg 32040 cgacggtctt cgtcctcgcc cccgcccccg ggagctccca acccccgtgc cccttcctct 32100 acggcgacac ggtccccgtc gtcgtcgggg cccgcgccgc ccttgggcgc gtccgccgcg 32160 ccccccgccc ccatgcgcgc cagcacgcga cgcagcgcct cctcgtcgca ctgttcgggg 32220 ctgacgaggc gccgcaagag cggcgtcgtc aggtggtggt cgtagcacgc gcggatgagc 32280 gcctcgatct gatcttcggg tgacgtggcc tgaccgccga ttattagggc gtccaccata 32340 tccagcgccg ccaggtggct cccgaacgcg cgatcgaaat gctccgcccg ccgcccgaac 32400 agcgccagtt ccacggccac cgcggcggtc tcctgctgca actcgcgccg cgccagcgcg 32460 gtcaggttgc tggcaaacgc gtccatggtg gtctggccgg cgcggtcgcc ggacgcgagc 32520 cagaatcgca attcgctgat ggcgtacagg ccgggcgtgg tggcctgaaa cacgtcgtgc 32580 gcctccagca gggcgtcggc ctccttgcgg accgagtcgt tctcgggcga cgggtggggc 32640 tgcccgtcgc cccccgcggt ccgggccagc gcatggtcca acacggagag cgcccgcgcg 32700 cggtcggcgt ccgacagccc ggcggcgtgg ggcaggtacc gccgcagctc gttggcgtcc 32760 agccgcacct gcgcctgctg ggtgacgtgg ttacagatac ggtccgccag gcggcgggcg 32820 atcgtcgccc cctggttcgc cgtcacacac agttcctcga aacagaccgc gcaggggtgg 32880 gacgggtcgc taagctccgg ggggacgata aggcccgacc ccaccgcccc caccataaac 32940 tcccgaacgc gctccagcgc ggcggtggcg ccgcgcgagg gggtgatgag gtggcagtag 33000 tttagctgct ttagaaagtt ctcgacgtcg tgcaggaaac acagctccat atggacggtc 33060 ccgccatacg tatccagcct gacccgttgg tgatacggac agggtcgggc caggcccatg 33120 gtctccgtga aaaacgccgc gacgtctccc gcggtcgcga acgtctccag gctgcccagg 33180 agccgctcgc cctcgcgcca cgcgtactct agcagcaact ccagggtgac cgacagcggg 33240 gtgagaaagg ccccggcctg ggcctccagg cccggcctca gacgacgccg cagcgcccgc 33300 acctgaagcg cgttcagctt cagttggggg agcttccccc gtccgatgtg ggggtcgcac 33360 cgccggagca gctctatctg aaacacatag gtctgcacct gcccgagcag ggctaacaac 33420 ttttgacggg ccacggtggg ctcggacacc ggggcggcca tctcgcggcg ccgatctgta 33480 ccgcggccgg agtatgcggt ggaccgaggc ggtccgtacg ctacccggcg tctggctgag 33540 ccccggggtc cccctcttcg gggcggcctc ccgcgggccc gccgaccggc aagccgggag 33600 tcggcggcgc gtgcgtttct gctctattcc cagacaccgc ggagaggaat cacggcccgc 33660 ccagagatat agacacggaa cacaaacaag cacggatgtc gtagcaataa tttattttac 33720 acacattccc cgccccgccc taggttcccc caccccccaa cccctcacag catatccaac 33780 gtcaggtctc cctttttgtc ggggggcccc tccccaaacg ggtcatcccc gtggaacgcc 33840 cgtttgcggc cggcaaatgc cggtcccggg gcccccgggc cgccgaacgg cgtcgcgttg 33900 tcgtcctcgc agccaaaatc cccaaagtta aacacctccc cggcgttgcc gagttggctg 33960 actagggcct cggcctcgtg cgccacctcc agggccgcgt ccgtcgacca ctcgccgttg 34020 ccgcgctcca gggcacgcgc ggtcagctcc atcatctcct cgcttaggta ctcgtcctcc 34080 aggagcgcca gccagtcctc gatctgcagc tgctgggtgc ggggccccag gcttttcacg 34140 gtcgccacga acacgctact ggcgacggcc gccccgccct cggagataat gccccggagc 34200 tgctcgcaca gcgagctttc gtgcgctccg ccgccgaggc ttgaggccgc gcacacaaac 34260 ccggcccggg gacaggccag gacgaacttg cgggtgcggt caaaaataag gagcgggcac 34320 gcgtttttgc cgcccatcag gctggcccag ttcccggcct gaaacacacg gtcgttgccg 34380 gccatgccgt agtacttgct gatgctcaac cccaacacga ccatggggcg cgccgccatg 34440 acgggccgca gcaggttgca gctggcgaac atggacgtcc acgcgcccgg atgcgcgtcc 34500 acggcgtcca tcagcgcgcg ggccccggcc tccaggcccg ccccgccctg cgcggaccac 34560 gcggccgcag cctgcacgct ggggggacgg cgggaccccg cgatgatggc cgtaagggtg 34620 ttgatgaagt atgtcgagtg atcgcagtac cgcagaatct ggtttgccat gtagtacatc 34680 gccagctcgc tcacgttgtt gggggccagg ttaataaagt ttatcgcgcc gtagtccagg 34740 gaaaactttt taatgaacgc gatggtctcg atgtcctcgc gcgacaggag ccgggcggga 34800 agctggttgc gttggagggc cgtccagaac cactgcgggt tcggctggtt ggaccccggg 34860 ggcttgccgt tggggaagat ggccgcgtgg aactgcttca gcagaaagcc cagcggtccg 34920 aggaggatgt ccacgcgctt gtcgggcttc tggtaggcgc tctggaggct ggcgacccgc 34980 gccttggcgg cctcggacgc gttggcgctc gcgcccgcga acaacacgcg gctcttgacg 35040 cgcagctcct tgggaaaccc cagggtcacg cgggcaacgt cgccctcgaa gctgctctcg 35100 gcgggggccg tctggccggc cgttaggctg ggggcgcaga tagccgcccc ctccgagagc 35160 gcgaccgtca gcgttttggc cgacagaaac ccgttgttaa acatgtccat cacgcgccgc 35220 cgcagcaccg gttggaattg attgcgaaag ttgcgcccct cgaccgactg cccggcgaac 35280 accccgtggc actgactcag ggccaggtcc tggtacacgg cgaggttgga tcgccgcccg 35340 agaagctgaa gcagggggca cggcccgcac gcgtacgggt ccagcgtcag ggacatggcg 35400 tggttggcct cgcccagacc gtcgcgaaac ttgaagttcc tcccctccac caggttgcgc 35460 atcagctgct ccacctcgcg gtccacgacc tgcctgacgt tgttcaccac cgtatgcagg 35520 gcctcgcggt tggtgatgat ggtctccagc cgccccatgg ccgtggggac cgcctggtcc 35580 acgtactgca gggtctcgag ttcggccatg acgcgctcgg tcgccgcgcg gtacgtctcc 35640 tgcatgatgg tccgggcggt ctcggatccg tccgcgcgct tcagggccga gaaggcggcg 35700 tagtttccca gcacgtcgca gtcgctgtac atgctgttca tggtcccgaa gacgccgatg 35760 gctccgcggg cggcgctggc gaactttgga tggcgcgccc ggaggcgcat gagcgtcgtg 35820 tgtacgcagg cgtggcgcgt gtcgaaggtg cataggttac agggcacgtc ggtctggttg 35880 gagtccgcga cgtatcgaaa cacgtccatc tcctggcgcc cgacgatcac ggcgccgtcg 35940 cagcgctcca ggtaaaacag catcttggcc agcagcgccg gggaaaaccc acacagcatg 36000 gccaggtgct cgccggcaaa ttcctgggtt ccgccgacga ggggcgcggt gggccgaccc 36060 tcgaacccgg gcaccacgtg tccctcgcgg tccacctgtg ggttggccgc cacgtgggtc 36120 ccgggcacga ggaagaagcg gtaaaaggag ggtttgctgt ggtcctttgg gtccgccggg 36180 ccggcgtcgt ccacctcggt gagatggagg gccgagttgg tgctaaatac catggccccc 36240 acgagtcccg cggcgcgcgc caggtacgcc ccgacggcgt tggcgcgggc cgcggccgtg 36300 tcctggccct cgaacagcgg ccacgcggag atgtcggtgg gcggctcgtc aaagacggcc 36360 atcgacacga tagactcgag ggccagggcg gcgtctccgg ccatgacgga ggccaggcgc 36420 tgttcgaacc cgcccgccgc gcccttgccg ccgccgtcgc gcccgccccg cggggtctta 36480 ccctggctgg cttcgaaggc cgtgaacgta atgtcggcgg ggagggcggc gccctcgtgg 36540 ttttcgtcaa acgccaggtg ggcggccgcg cgggccacgg cgtccacgtt tcggcatcgc 36600 agtgccacgg cggcgggtcc cacgaccgcc tcgaacagga ggcggttgag ggggcggtta 36660 aaaaacggaa gcgggtaggt aaatttctcc ccgatcgatc ggtggttggc gttgaacggc 36720 tctgcgatga cacggctaaa atccggcatg aacagctgca acgggtacac gggtatgcgg 36780 tgcacctccg ccccgcctat ggttaccttg tccgagcctc ccaggtgcag aaaggtgttg 36840 ttgatgcaca cggcctcctt gaagccctcg gtaacgacca gatacaggag ggcgcggtcc 36900 gggtccaggc cgaggcgctc acacagcgcc tcccccgtcg tctcgtgttt gaggtcgccg 36960 ggccgggggg tgtagtccga aaagccaaaa tggcggcgtg cccgctcgca aagtcgcgtc 37020 aggttcgggg cctgggtgct ggggtccagg tgccggccgc cgtgaaagac gtacacggac 37080 gagctgtagt gcgagggcgt cagtttcagg gacaccgcgg tacccccgag ccccgtcgtg 37140 cgagaaccca cgaccacggc cacgttggcc tcaaagccgc tctccacggt caggcccacg 37200 accaggggcg ccacggcgac gtcggaatcg ccgctgcgtg ccgacagtaa cgccagaagc 37260 tcgatgcctt cggacggaca cgcgcgagcg tacacgtatc ccaggggccc gggggggacc 37320 ttgatggtgg ttgccgtctt gggctttgtc tccatgtcct tttgtcaatc ggtccgcgaa 37380 cggaggtaat cccggcacga cgacggacgc ccgacaaggt atgtctcccg agcgtcaaaa 37440 tccggggggg ggcggcgacg gtcaagggga gggttggaga ccggggttgg ggaatgaatc 37500 cctccccttc accgacaacc ccccgggtaa ccacggggtc gccgatgaac cccggcggcc 37560 ggcaacgcgg ggtccctgcg agaggcacag atgcttacgg tcaggtgctc cgggtcgggt 37620 gcgtctggta tgcggttggt atatgtacac tttacctggg ggcgtgccgg tccgccccag 37680 cccctcccac gccccgcgcg tcatcagccg gtgggcgtgg ccgctattat aaaaaaagtg 37740 agaacgcgaa gcgttcgcac tttgtcctaa taatatatat attattagga caaagtgcga 37800 acgcttcgcg ttctcacttt ttttataata gcggccacgc ccaccggcta cgtcactctc 37860 ctgtcggccg ccggcggtcc ataagcccgg ccggccgggc cgacgcgaat aaaccgggcc 37920 gccggccggg gcgccgcgca gcagctcgcc gcccggatcc gccagacaaa caaggccctt 37980 gcacatgccg gcccgggcga gcctgggggt ccggtaattt tgccatccca cccaagcggc 38040 tttttgggtt tttctcttcc cccctcccca cattcccctc tttaggggtt cgggtgggaa 38100 caaccgcgat gttttccggt ggcggcggcc cgctgtcccc cggaggaaag tcggcggcca 38160 gggcggcgtc cgggtttttt gcgcccgccg gccctcgcgg agccagccgg ggacccccgc 38220 cttgtttgag gcaaaacttt tacaacccct acctcgcccc agtcgggacg caacagaagc 38280 cgaccgggcc aacccagcgc catacgtact atagcgaatg cgatgaattt cgattcatcg 38340 ccccgcgggt gctggacgag gatgcccccc cggagaagcg cgccggggtg cacgacggtc 38400 acctcaagcg cgcccccaag gtgtactgcg ggggggacga gcgcgacgtc ctccgcgtcg 38460 ggtcgggcgg cttctggccg cggcgctcgc gcctgtgggg cggcgtggac cacgccccgg 38520 cggggttcaa ccccaccgtc accgtctttc acgtgtacga catcctggag aacgtggagc 38580 acgcgtacgg catgcgcgcg gcccagttcc acgcgcggtt tatggacgcc atcacaccga 38640 cggggaccgt catcacgctc ctgggcctga ctccggaagg ccaccgggtg gccgttcacg 38700 tttacggcac gcggcagtac ttttacatga acaaggagga ggtcgacagg cacctacaat 38760 gccgcgcccc acgagatctc tgcgagcgca tggccgcggc cctgcgcgag tccccgggcg 38820 cgtcgttccg cggcatctcc gcggaccact tcgaggcgga ggtggtggag cgcaccgacg 38880 tgtactacta cgagacgcgc cccgctctgt tttaccgcgt ctacgtccga agcgggcgtg 38940 tgctgtcgta cctgtgcgac aacttctgcc cggccatcaa gaagtacgag ggtggggtcg 39000 acgccaccac ccggttcatc ctggacaacc ccgggttcgt caccttcggc tggtaccgtc 39060 tcaaaccggg ccggaacaac acgctagccc agccggcggc cccgatggcc ttcgggacat 39120 ccagcgacgt cgagtttaac tgtacggcgg acaacctggc catcgagggg ggcatgagcg 39180 acctaccggc atacaagctc atgtgcttcg atatcgaatg caaggcgggg ggggaggacg 39240 agctggcctt tccggtggcc gggcacccgg aggacctggt catccagata tcctgtctgc 39300 tctacgacct gtccaccacc gccctggagc acgtcctcct gttttcgctc ggttcctgcg 39360 acctccccga atcccacctg aacgagctgg cggccagggg cctgcccacg cccgtggttc 39420 tggaattcga cagcgaattc gagatgctgt tggccttcat gacccttgtg aaacagtacg 39480 gccccgagtt cgtgaccggg tacaacatca tcaacttcga ctggcccttc ttgctggcca 39540 agctgacgga catttacaag gtccccctgg acgggtacgg ccgcatgaac ggccggggcg 39600 tgtttcgcgt gtgggacata ggccagagcc acttccagaa gcgcagcaag ataaaggtga 39660 acggcatggt gaacatcgac atgtacggga ttataaccga caagatc 39707 <212> Type: DNA <211> Length: 39707 ...

SequenceName：cos28

SequenceDescription: Custom Codon ----------- Sequence Name: cos28 Seq9: [Electronic version File name: cos48 (Seq9). WorkFile] Sequence Name: cos48 Sequence -------- <213> OrganismName: Human herpes simplex virus type 1 <400> PreSequenceString: atccttggtt ggagggggcg ctcggggccc caagcgtgac tacggcccta ccggcgcgac 60 gccgagggcg gtccctcgtc tatgccggcg agctgacgcc ggttcagacg gaacacgggg 120 acggcgtacg agaagccatc gccttccttc caaaacgcga ggaggatgcc ggtttcgaca 180 ttgtcgtccg tcgcccggtc accgtcccgg caaacggcac cacggtcgtg cagccatccc 240 tccgcatgct ccacgcggac gccgggcccg cggcctgcta tgtgttgggg cggtcgtcgc 300 tcaacgcccg cggcctcctg gtcgttccta cgcgctggct ccccgggcac gtatgtgcgt 360 ttgttgttta caaccttacg ggggttcctg tgaccctcga ggccggcgcc aaggtcgccc 420 agctcctggt tgcgggggcg gacgctcttc cttggatccc cccggacaac tttcacggga 480 ccaaagcgct tcgaaactac cccaggggtg ttccggactc aaccgccgaa cccaggaacc 540 cgccgctcct ggtgtttacg aacgagtttg acgcggaggc ccccccgagc gagcgcggga 600 ccgggggttt tggttctacc ggtatttagc ccacagcttt gggttcgttc cgggcaataa 660 aaaacgtttg tatcgcatct ttcctgtgtg tagttgttta tgttggatgc ctgtgggtct 720 atcacacccg cccctccatc ccacaaacac aaaacacacg ggttggatga aaacacgcat 780 ttattgaccc aaaacacacg gagctgctcg agatgggcca gggcgaggtg cggttgggga 840 ggctgtaggt ctgggaacgg acacgcgggg acacgattcc ggtttggggt ccgggagggc 900 gtcgccgttt cgggcggcag gcgccagcgt aacctccggg ggcggcgtgt gggggtgccc 960 caaggagggc gcctcggtca ccccaatccc ccccgaccgg gttcccccgg caaccccgaa 1020 ggcggagagg ccaagggccc gttcggcgat ggccacatcc tccatgacca cgtcactctc 1080 ggccatgctc cgaatagcct gggagacgag cacatccgcg gacttgtcag ccgcccccac 1140 ggacatgtac atctgcagga tggtggccat acacgtgtcc gccaggcgcc gcatcttgtc 1200 ctgatgggcc gccacggccc cgtcgatcgt gggggcctcg aacccggggt ggtggcgcgc 1260 cagtcgttct aggttcacca tgcaggcgtg gtacgtgcgg gccaaggcgc gggccttcac 1320 gaggcgtcgg gtgtcgtcca gggaccccag ggcgtcatcg agcgtgatgg gggcgggaag 1380 tagcgcgtta acgaccgcca gggcctcctg cagccgcggc tccgcctccg agggcggaac 1440 ggccgcgcgg atcatctcat attgttcctc ggggcgcgct ccccagccac atatagcccc 1500 gagaagagaa gccatcgcgg gcgggtactg gcccttgggc gcgcggacgc aatggggcag 1560 gaagacggga accgcgggga gaggcgggcg gccgggactc ccgtggaggt gaccgcgctt 1620 tatgcgaccg acgggtgcgt tattacctct tcgatcgccc tcctcacaaa ctctctactg 1680 ggggccgagc cggtttatat attcagctac gacgcataca cgcacgatgg ccgtgccgac 1740 gggcccacgg agcaagacag gttcgaagag agtcgggcgc tctaccaagc gtcgggcggg 1800 ctaaatggcg actccttccg agtaaccttt tgtttattgg ggacggaagt gggtgggacc 1860 caccaggccc gcgggcgaac ccgacccatg ttcgtctgtc gcttcgagcg agcggacgac 1920 gtcgccgcgc tacaggacgc cctggcgcac gggaccccgc tacaaccgga ccacatcgcc 1980 gccaccctgg acgcggaggc cacgttcgcg ctgcatgcga acatgatcct ggctctcacc 2040 gtggccatca acaacgccag cccccgcacc ggacgcgacg ccgccgcggc gcagtatgat 2100 cagggcgcgt ccctacgctc gctcgtgggg cgcacgtccc tgggacaacg cggccttacc 2160 acgctatacg tccaccacga ggtgcgcgtg cttgccgcgt accgcagggc gtattatgga 2220 agcgcgcaga gtcccttctg gtttcttagc aaattcgggc cggacgaaaa aagcctggtg 2280 ctcaccactc ggtactacct gcttcaggcc cagcgtctgg ggggcgcggg ggccacgtac 2340 gacctgcagg ccatcaagga catctgcgcc acctacgcga ttccccacgc cccccgcccc 2400 gacaccgtca gcgctgcgtc cctgacctcg tttgccgcca tcacgcggtt ctgttgcacg 2460 agccagtacg cccgcggggc cgcggcggcc gggtttccgc tttacgtgga gcgccgtatt 2520 gcggccgacg tccgcgagac cagtgcgctg gagaagttca taacccacga tcgcagttgc 2580 ctgcgcgtgt ccgaccgtga attcattacg tacatctacc tggcccattt tgagtgtttc 2640 agccccccgc gcctagccac gcatcttcgg gccgtgacga cccacgaccc caaccccgcg 2700 gccagcacgg agcagccctc gcccctgggc agggaggccg tggaacaatt tttttgtcac 2760 gtgcgcgccc aactgaatat cggggagtac gtcaaacaca acgtgacccc ccgggagacc 2820 gtcctggatg gcgatacggc caaggcctac ctgcgcgctc gcacgtacgc gcccggggcc 2880 ctgacgcccg cccccgcgta ttgcggggcc gtggactccg ccaccaaaat gatggggcgt 2940 ttggcggacg ccgaaaagct cctggtcccc cgcgggtggc ccgcgtttgc gcccgccagt 3000 cccggggagg acacggcggg cggcacgccg cccccacaga cctgcggaat tgtcaagcgc 3060 ctcctgagac tggccgccac ggaacagcag ggccccacac ccccggcgat cgcggcgctt 3120 atccgtaatg cggcggtgca gactcccctg cccgtctacc ggatatccat ggtccccacg 3180 ggacaggcat ttgccgcgct ggcctgggac gactgggccc gcataacgcg ggacgctcgc 3240 ctggccgaag cggtcgtgtc cgccgaagcg gcggcgcacc ccgaccacgg cgcgctgggc 3300 aggcggctca cggatcgcat ccgcgcccag ggccccgtga tgccccctgg cggcctggat 3360 gccggggggc agatgtacgt gaatcgcaac gagatattca acggcgcgct ggcaatcaca 3420 aacatcatcc tggatctcga catcgccctg aaggagcccg tcccctttcg ccggctccac 3480 gaggccctgg gccactttag gcgcggggct ctggctgcgg ttcagctcct gtttcccgcg 3540 gcccgcgtgg accccgacgc atatccctgt tattttttca aaagcgcatg tcggcccggc 3600 ccggcgtccg tgggttccgg cagcggactc ggcaacgacg acgacgggga ctggtttccc 3660 tgctacgacg acgccggtga tgaggagtgg gcggaggacc cgggcgccat ggacacatcc 3720 cacgatcccc cggacgacga ggttgcctac tttgacctgt gccacgaagt cggccccacg 3780 gcggaacctc gcgaaacgga ttcgcccgtg tgttcctgca ccgacaagat cggactgcgg 3840 gtgtgcatgc ccgtccccgc cccgtacgtc gtccacggtt ctctaacgat gcggggggtg 3900 gcacgggtca tccagcaggc ggtgctgttg gaccgagatt ttgtggaggc catcgggagc 3960 tacgtaaaaa acttcctgtt gatcgatacg ggggtgtacg cccacggcca cagcctgcgc 4020 ttgccgtatt ttgccaaaat cgcccccgac gggcctgcgt gcggaaggct gctgccagtg 4080 tttgtgatcc cccccgcctg caaagacgtt ccggcgtttg tcgccgcgca cgccgacccg 4140 cggcgcttcc attttcacgc cccgcccacc tatctcgctt ccccccggga gatccgtgtc 4200 ctgcacagcc tgggtgggga ctatgtgagc ttctttgaaa ggaaggcgtc ccgcaacgcg 4260 ctggaacact ttgggcgacg cgagaccctg acggaggtcc tgggtcggta caacgtacag 4320 ccggatgcgg gggggaccgt cgaggggttc gcatcggaac tgctggggcg gatagtcgcg 4380 tgcatcgaaa cccactttcc cgaacacgcc ggcgaatatc aggccgtatc cgtccggcgg 4440 gccgtcagta aggacgactg ggtcctccta cagctagtcc ccgttcgcgg taccctgcag 4500 caaagcctgt cgtgtctgcg ctttaagcac ggccgggcga gtcgcgccac ggcgcggaca 4560 ttcgtcgcgc tgagcgtcgg ggccaacaac cgcctgtgcg tgtccttgtg tcagcagtgc 4620 tttgccgcca aatgcgacag caaccgcctg cacacgctgt ttaccattga cgccggcacg 4680 ccatgctcgc cgtccgttcc ctgcagcacc tctcaaccgt cgtcttgata acggcgtacg 4740 gcctcgtgct cgtgtggtac accgtcttcg gtgccagtcc gctgcaccga tgtatttacg 4800 cggtacgccc caccggcacc aacaacgaca ccgccctcgt gtggatgaaa atgaaccaga 4860 ccctattgtt tctgggggcc ccgacgcacc cccccaacgg gggctggcgc aaccacgccc 4920 atatctgcta cgccaatctt atcgcgggta gggtcgtgcc cttccaggtc ccacctgacg 4980 ccatgaatcg tcggatcatg aacgtccacg aggcagttaa ctgtctggag accctatggt 5040 acacacgggt gcgtctggtg gtcgtagggt ggttcctgta tctggcgttc gtcgccctcc 5100 accaacgccg atgtatgttt ggcgtcgtga gtcccgccca caagatggtg gccccggcca 5160 cctacctctt gaactacgca ggccgcatcg tatcgagcgt gttcctgcag tacccctaca 5220 cgaaaattac ccgcctgctc tgcgagctgt cggtccagcg gcaaaacctg gttcagttgt 5280 ttgagacgga cccggtcacc ttcttgtacc accgccccgc catcggggtc atcgtaggct 5340 gcgagttgat gctacgcttt gtggccgtgg gtctcatcgt cggcaccgct ttcatatccc 5400 ggggggcatg tgcgatcaca taccccctgt ttctgaccat caccacctgg tgttttgtct 5460 ccaccatcgg cctgacagag ctgtattgta ttctgcggcg gggcccggcc cccaagaacg 5520 cagacaaggc cgccgccccg gggcgatcca aggggctgtc gggcgtctgc gggcgctgct 5580 gttccatcat cctctcgggc atcgcagtgc gattgtgtta tatcgccgtg gtggccgggg 5640 tggtgctcgt ggcgcttcac tacgagcagg agatccagag gcgcctgttt gatgtatgac 5700 gtcacatcca ggccggcgga aaccgtaacg gcatatgcaa attggaaact gtcctgtctt 5760 ggggcccacc cacccgacgc gtcatatgca aatgaaaatc ggtcccccga ggccacgtgt 5820 agcctggatc ccaacgaccc cgcccatggg tcccaattgg ccgtcccgtt accaagacca 5880 acccagccag cgtatccacc cccgcccggg tccccgcgga agcggaacgg ggtatgtgat 5940 atgctaatta aatacatgcc acgtacttat ggtgtctgat tggtccttgt ctgtgccgga 6000 ggtggggcgg gggccccgcc cggggggcgg aacgaggagg ggtttgggag agccggcccc 6060 ggcaccacgg gtataaggac atccaccacc cggccggtgg tggtgtgcag ccgtgttcca 6120 accacggtca cgcttcggtg cctctccccg attcgggccc ggtcgctcgc taccggtgcg 6180 ccaccaccag aggccatatc cgacacccca gccccgacgg cagccgacag cccggtcatg 6240 gcgactgaca ttgatatgct aattgacctc ggcctggacc tctccgacag cgatctggac 6300 gaggaccccc ccgagccggc ggagagccgc cgcgacgacc tggaatcgga cagcagcggg 6360 gagtgttcct cgtcggacga ggacatggaa gacccccacg gagaggacgg accggagccg 6420 atactcgacg ccgctcgccc ggcggtccgc ccgtctcgtc cagaagaccc cggcgtaccc 6480 agcacccaga cgcctcgtcc gacggagcgg cagggcccca acgatcctca accagcgccc 6540 cacagtgtgt ggtcgcgcct cggggcccgg cgaccgtctt gctcccccga gcagcacggg 6600 ggcaaggtgg cccgcctcca acccccaccg accaaagccc agcctgcccg cggcggacgc 6660 cgtgggcgtc gcaggggtcg gggtcgcggt ggtcccgggg ctgccgatgg tttgtcggac 6720 ccccgccggc gtgcccccag aaccaatcgc aaccctgggg gaccccgccc cggggcgggg 6780 tggacggacg gccccggcgc cccccatggc gaggcgtggc gcggcagtga gcagcccgac 6840 ccacccggag gccagcggac acggggcgtg cgccaagcac cccccccgct aatgacgctg 6900 gcgattgccc ccccgcccgc ggacccccgc gccccggccc cggagcgaaa ggcgcccgcc 6960 gccgacacca tcgacgccac cacgcggttg gtcctgcgct ccatctccga gcgcgcggcg 7020 gtcgaccgca tcagcgagag ctttggccgc agcgcacagg tcatgcacga cccctttggg 7080 gggcagccgt ttcccgccgc gaatagcccc tgggccccgg tgctggcggg ccaaggaggg 7140 ccctttgacg ccgagaccag acgggtctcc tgggaaacct tggtcgccca cggcccgagc 7200 ctctatcgca cttttgccgg caatcctcgg gccgcatcga ccgccaaggc catgcgcgac 7260 tgcgtgctgc gccaagaaaa tttcatcgag gcgctggcct ccgccgacga gacgctggcg 7320 tggtgcaaga tgtgcatcca ccacaacctg ccgctgcgcc cccaggaccc cattatcggg 7380 acgaccgcgg ctgtgctgga taacctcgcc acgcgcctgc ggccctttct ccagtgctac 7440 ctgaaggcgc gaggcctgtg cggcctggac gaactgtgtt cgcggcggcg tctggcggac 7500 attaaggaca ttgcatcctt cgtgtttgtc attctggcca ggctcgccaa ccgcgtcgag 7560 cgtggcgtcg cggagatcga ctacgcgacc cttggtgtcg gggtcggaga gaagatgcat 7620 ttctacctcc ccggggcctg catggcgggc ctgatcgaaa tcctagacac gcaccgccag 7680 gagtgttcga gtcgtgtctg cgagttgacg gccagtcaca tcgtcgcccc cccgtacgtg 7740 cacggcaaat atttttattg caactccctg ttttaggtac aataaaaaca aaacatttca 7800 aacaaatcgc ccctcgtgtt gtccttcttt gctcatggcc ggcggggcgt gggtcacggc 7860 agatggcggg ggtgggcccg gcgtacggcc tgggtgggcg gagggaacta acccaacgta 7920 taaatccgtc cccgttccaa ggccggtgtc atagtgccct taggagcttc ccgcccgggc 7980 gcatcccccc ttttgcacta tgacagcgac ccccctcacc aacctgttct tacgggcccc 8040 ggacataacc cacgtggccc ccccttactg cctcaacgcc acctggcagg ccgaaacggc 8100 catgcacacc agcaaaacgg actccgcttg cgtggccgtg cggagttacc tggtccgcgc 8160 ctcctgtgag accagcggca caatccactg ctttttcttt gcggtataca aggacaccca 8220 ccacacccct ccgctgatta ccgagctccg caactttgcg gacctggtta accacccgcc 8280 ggtcctacgc gaactggagg ataagcgcgg ggtgcggctg cggtgtgcgc ggccgtttag 8340 cgtcgggacg attaaggacg tctctgggtc cggcgcgtcc tcggcgggag agtacacgat 8400 aaacgggatc gtgtaccact gccactgtcg gtatccgttc tcaaaaacat gctggatggg 8460 ggcctccgcg gccctacagc acctgcgctc catcagctcc agcggcatgg ccgcccgcgc 8520 ggcagagcat cgacgcgtca agattaaaat taaggcgtga tctccaaccc ccccatgaat 8580 gtgtgtaacc ccccocaaaa aaataaagag ccgtaaccca accaaaccag gcgtggtgtg 8640 agtttgtgga cccaaagccc tcagagacaa cgcgacaggc cagtatggac cgtgatactt 8700 ttatttatta actcacaggg gcgcttaccg ccacaggaat accagaataa tgaccaccac 8760 aatcgcgacc accccaaata cagcatggcg ccacaccacg ccacaacagc cctgtcgccg 8820 gtatggggca tgatcagacg agccgcgccg cgcgttgggc cctgtacagc tcgcgcgaat 8880 tgaccctagg aggccgccac gcgcccgagt tttgcgttcg tcgctggtcg tcgggcgcca 8940 aagccccgga cggctgttcg gtcgaacgaa cggccacgac agtggcatag gttggggggt 9000 ggtccgacat agcctcggcg tacgtcggga ggcccgacaa gaggtccctt gtgatgtcgg 9060 gtggggccac aagcctggtt tccggaagaa acaggggggt tgccaataac ccgccagggc 9120 caaaactccg gcgctgcgca cgtcgttcgg cgcggcgccg ggcgcgccga gcggctcgct 9180 gggcggcttg gcgtgagcgg ccccgctccg acgcctcgcc ctctccggag gaggttggcg 9240 gaattggcac ggacaacagg ggcccagcag agtacggtgg aggtgggtcc gtgggggtgt 9300 ccagatcaat aacgacaaac ggcccctcgt tcctaccaga caagctatcg taggggggcg 9360 ggggatcagc aaacgcgttc cccgcgctcc ataaacccgc gtcgggttgc gccgcctccg 9420 aagccatgga tgcgccccaa agccacgact cccgcgcgct aggtccttgg ggtaatggaa 9480 aaggccctac tccccatcca agccagccaa gttaacgggc tacgccttcg ggaatgggac 9540 tggcaccccg gcggattttg ttgggctggc atgcgtcgcc caaccgaggg ccgcgtccac 9600 gggacgcgcc ttttataacc ccgggggtca ttcccaacga tcacatgcaa tctaactggc 9660 tcccctctcc ccccctctcc cctctccccc cctctcccct ctccccccct ctcccctctc 9720 cccccctctc ccctctcccc ccctctcccc tctccccccc tctcccctct ccccccctct 9780 cccctctccc cccctctccc ctctcccccc ctctcccctc tccccccctc tcccctctcc 9840 cctctgctct ttccccgtga cacccgacgc tgggggcgtg gctgccggga ggggccgcgg 9900 atgggcgggc ctacttggtt tcccgccccc cccccccccc cccgaaccgc cccgccggct 9960 ttgcccccct ttgatcccct gctaccccca acccgtgctg gtggtgcggg ttgggggggg 10020 atgtgggcgg gggtgcgcgg gaggtgtcgg tggtggtggt ggtggtggta gtaggaatgg 10080 tggtgagggg gggggggcgc tggttggtca aaaaagggag ggacgggggc cggcagaccg 10140 acggcgacaa cgctccccgg cggccgggtc gcggctctta cgagcggccc ggcccgcgct 10200 cccacccccc gggccgtgtc cttgctttcc ccccgtctcc cccccccccg ccttctcctc 10260 ctcctcctcg tttttccaaa ccccgcccac ccggcccggc ccggcccggc ccggcccggc 10320 caccgccgcc cacccaccca cctcgggata cccagccccg gtcccccgtt ccccgggggc 10380 cgttatctcc agcgccccgt ccggcgcgcc gccccccgcc gctaaacccc atcccgcccc 10440 cgggacccca catataagcc cccagccaca cgcaagaaca gacacgcaga acggctgtgt 10500 ttatttaaat aaaccaatgt cggaataaac aaacacaaac acccgcgacg gggggacgga 10560 ggggacggag ggagggggtg acgggggacg ggaacagaca caaaaacaac cacaaaaaac 10620 aaccacccac cgacaccccc accccagtct cctcgccttc tcccacccac cccacgcccc 10680 cactgagccc ggtcgatcga cgagcacccc cgcccacgcc cccgcccctg ccccggcgac 10740 ccccggcccg cacgatcccg acaacaataa caaccccaac ggaaagcggc ggggtgttgg 10800 gggaggcgag gaacaaccga ggggaacggg ggatggaagg acgggaagtg gaagtcctga 10860 tacccatcct acacccccct gccttccacc ctccggcccc ccgcgagtcc acccgccggc 10920 cggctaccga gaccgaacac ggcggccgcc gcagccgccg cagccgccgc cgacaccgca 10980 gagccggcgc gcgcactcac aagcggcaga ggcagaaagg cccagagtca ttgtttatgt 11040 ggccgcgggc cagcagacgg cccgcgacac cccccccccg cccgtgtggg tatccggccc 11100 cccgccccgc gccggtccat taagggcgcg cgtgcccgcg agatatcaat ccgttaagtg 11160 ctctgcagac aggggcaccg cgcccggaaa tccattaggc cgcagacgag gaaaataaaa 11220 ttacatcacc tacccacgtg gtgctgtggc ctgtttttgc tgcgtcatct cagcctttat 11280 aaaagcgggg gcgcggccgt gccgatcgcg ggtggtgcga aagactttcc gggcgcgtcc 11340 gggtgccgcg gctctccggg cccccctgca gccggggcgg ccaaggggcg tcggcgacat 11400 cctcccccta agcgccggcc ggccgctggt ctgttttttc gttttccccg tttcgggggt 11460 ggtgggggtt gcggtttctg tttctttaac ccgtctgggg tgtttttcgt tccgtcgccg 11520 gaatgtttcg ttcgtctgtc ccctcacggg gcgaaggccg cgtacggccc gggacgaggg 11580 gcccccgacc gcggcggtcc gggccccgtc cggacccgct cgccggcacg cgacgcgaaa 11640 aaggcccccc ggaggctttt ccgggttccc ggcccggggc ctgagatgaa cactcggggt 11700 taccgccaac ggccggcccc cgtggcggcc cggcccgggg ccccggcgga cccaaggggc 11760 cccggcccgg ggccccacaa cggcccggcg catgcgctgt ggtttttttt tcctcggtgt 11820 tctgccgggc tccatcgcct ttcctgttct cgcttctccc cccccccttc ttcaccccca 11880 gtaccctcct ccctcccttc ctcccccgtt atcccactcg tcgagggcgc cccggtgtcg 11940 ttcaacaaag acgccgcgtt tccaggtagg ttagacacct gcttctcccc aatagagggg 12000 ggggacccaa acgacagggg gcgccccaga ggctaaggtc ggccacgcca ctcgcgggtg 12060 ggctcgtgtt acagcacacc agcccgttct tttccccccc tcccaccctt agtcagactc 12120 tgttacttac ccgtccgacc accaactgcc cccttatcta agggccggct ggaagaccgc 12180 cagggggtcg gccggtgtcg ctgtaacccc ccacgccaat gacccacgta ctccaagaag 12240 gcatgtgtcc caccccgcct gtgtttttgt gcctggctct ctatgcttgg gtcttactgc 12300 ctgggggggg ggagtgcggg ggaggggggg tgtggaagga aatgcacggc gcgtgtgtac 12360 cccccctaaa gttgttccta aagcgaggat acggaggagt ggcgggtgcc gggggaccgg 12420 ggtgatctct ggcacgcggg ggtgggaagg gtcgggggag ggggggatgg agtaccggcc 12480 cacctggccg cgcgggtgcg cgtgcctttg cacaccaacc ccacgtcccc cggcggtctc 12540 taagaagcac cgccccccct ccttcatacc accgagcatg cctgggtgtg ggttggtaac 12600 caacacgccc atcccctcgt ctcctgtgat tctctggctg caccgcattc ttgttttcta 12660 actatgttcc tgtttctgtc tccccccccc ccacccctcc gccccacccc ccaacaccca 12720 cgtctgtggt gtggccgacc cccttttggg cgccccgtcc cgccccgcca cccctcccat 12780 cctttgttgc cctatagtgt agttaacccc ccccgccctt tgtggcggcc agaggccagg 12840 tcagtccggg cgggcaggcg ctcgcggaaa cttaacaccc acacccaacc cactgtggtt 12900 ctggctccat gccagtggca ggatgctttc ggggatcggt ggtcaggcag cccgggccgc 12960 ggctctgtgg ttaacaccag agcctgccca acatggcacc cccactccca cgcaccccca 13020 ctcccacgca cccccactcc cacgcacccc cactcccacg cacccccact cccacgcacc 13080 cccactccca cgcaccccca ctcccacgca cccccactcc cacgcacccc cactcccacg 13140 catccccgcg atacatccaa cacagacagg gaaaagatac aaaagtaaac ctttatttcc 13200 caacagacag caaaaatccc ctgagttttt ttttattagg gccaacacaa aagacccgct 13260 ggtgtgtggt gcccgtgtct ttcacttttc ccctccccga cacggattgg ctggtgtagt 13320 gggcgcggcc agagaccacc cagcgcccga cccccccctc cccacaaaca cggggggcgt 13380 cccttattgt tttccctcgt cccgggtcga cgccccctgc tccccggacc acgggtgccg 13440 agaccgcagg ctgcggaagt ccagggcgcc cactagggtg ccctggtcga acagcatgtt 13500 ccccacgggg gtcatccaga ggctgttcca ctccgacgcg ggggccgtcg ggtactcggg 13560 gggcatcacg tggttacccg cggtctcggg gagcagggtg cggcggctcc agccggggac 13620 cgcggcccgc agccgggtcg ccatgtttcc cgtctggtcc accaggacca cgtacgcccc 13680 gatgttcccc gtctccatgt ccaggatggg caggcagtcc cccgtgatag tcttgttcac 13740 gtaaggcgac agggcgacca cgctagagac ccccgagatg ggcaggtagc gcgtgaggcc 13800 gcccgcgggg acggccccgg aagtctccgc gtggcgcgtc ttccgggcac acttcctcgg 13860 cccccgcggc ccagaagcag cgcgggggcc gagggaggtt tcctcttgtc tccctcccag 13920 ggcaccgacg gccccgcccg aggaggcgga agcggaggag gacgcggccc cggcggcgga 13980 agaggcggcc cccgcggggg tcggggccga ggaggaagag gcagaggagg aagaggcgga 14040 ggccgccgag gacgtcaggg gggtcccggg cccaccctgg ccgcgccccc ccggccctga 14100 gtcggagggg gggtgcgtcg ccgccctctt ggcccctgcc ggcgcgaggg ggggacgcgt 14160 ggactggggg gaggggtttt cctggcccga cccgcgcctc ttcctcggac gcaccgccgc 14220 ctcctgctcg acagaggcgg cggaggggag cggggcggcg ccggaggggg cggcgccgcg 14280 ggagggcccg tgcccaccct ccacgcccgg cccccccgag ccgcgcgcca ccgtcgcacg 14340 cgcccggcac agactctgtt cttggttcgc ggcctgagcc agggacgagt gcgactgggg 14400 cacacggcgc gcgtccgcgg ggcgggcggc cggctccgcc ccgggggccg gggcgcgggg 14460 gccgggcccc ggaggcggcg ctcgcacgca cggggccacg gccgcgcggg ggcgcgcggg 14520 tcccgacgcg gccgcggacg cggggggccc ggggcggggg gcggagcctg gcatgggcgc 14580 cgcggggggc ctgtggggag aggccggggg ggagtcgctg atcactatgg ggtctctgtt 14640 gtttgcaagg ggggcgggtc tgttgacaag ggggcccgtc cggcccctcg gccgccccgc 14700 ctccgcttca acaaccccaa ccccaacccc aacccccccg gaggggccag acgccccccg 14760 cggcgccgcg gctcgcgact ggcgggagcc gccgccgccg ctgctgttgg tggtggtgtt 14820 ggtgttactg ctgccgtgtg gcccgatggg cgccgagggg ggcgctgtcc gagccgcggc 14880 cggctggggg gctgcgtgag acgccccgcc cgtcacgggg ggcgcggcgg cgcctctgcg 14940 tgggggggcg cggggcgtcc ggcggggggc gggcggtacg tagtctgctg caagagacaa 15000 cggggggcgc gatcaggtta cgccccctcc ccggcccgcc ctttcctcgc ccgcccgcct 15060 attcctccct ccccccccct cctcctcctc ctcccccagg gtccttgccg ccccccgcct 15120 caccgtcgtc caggtcgtcg tcatcctcgt ccgtggtggg ctccgggtgg gtgggcgaca 15180 gggccctcac cgtgtgcccc cccagggtca ggtaccgcgg ggcgaaccgc tgattgcccg 15240 tccagataaa gtccacggcc gtgcccgccc tgacggcctc ctcggcctcc atgcgggtct 15300 gggggtcgtt cacgatcggg atggtgctga acgacccgct gggcgtcacg cccactatca 15360 ggtacaccag cttggcgttg cacagcgggc aggtgttgcg caattgcatc caggttttca 15420 tgcacgggat gcagaagcgg tgcatgcacg ggaaggtgtc gcagcgcagg tggggcgcga 15480 tctcatccgt gcacacggcg cacacgtcgc cctcgtcgct ccccccgtcc tctcgagggg 15540 gggcgccccc gcaactgccg gggtcttcct cgcggggggg gctccccccc gagaccgccc 15600 ccccatccac gccctgcggc cccagcagcc ccgtctcgaa cagttccgtg tccgtgctgt 15660 ccgcctcgga ggcggagtcg tcgtcatggt ggtcggcgtc cccccgcccc cccacttcgg 15720 tctccgcctc agagtcgctg ctgtccggca ggtctcggtc gcagggaaac acccagacat 15780 ccggggcggg ctaaggggaa aaaagggggg cgggtaagaa tgggggggga tttcccgcgt 15840 caatcagcac ccacgagttc cccctctccc ccccccgcct cacaaagtcc tgcccccctg 15900 ctggcctcgg aagagggggg agaaaggggt ctgcaaccaa aggtggtctg ggtccgtcct 15960 ttggatcccg acccctcttc ttccctcttc tcccgccctc cagacgcacc ggagtcgggg 16020 gtcccacggc gtcccccaaa tatggcgggc ggctcctccc caccccccta gatgcgtgtg 16080 agtaaggggg gcctgcgtat gagtcagtgg ggaccacgcc cccaacacgg cgaccccggt 16140 ccttgtgtgt ttgttgtggg ggcgtgtctc tgtgtatgag tcagggggtc ccacggcgac 16200 cccgggccct gcgtctgagt caaaggggcc atgtgtatgt gttgggggtc tgtatatata 16260 aagtcagggg gtcacatggc gacccccaac agggcgaccc cggtccctgt atatataggg 16320 tcagggggtt ccgcaccccc taacatggcg cccccggtcc ctgtatatat agtgtcacgg 16380 ggttccacgc cccctaacat ggcgccccaa catggcgccc ggctcccgtg tatgagtggg 16440 ggtcccccaa catggcggcc ggttccagtg taagggtcgg gggtccccca acatggcgcc 16500 ccccaatatg gcgcccccca atatggcgcc ccagacatgg cgcccggccc ctcacctcgc 16560 gctgggggcg gccctcaggc cggcgggtac tcgctccggg gcggggctcc atgggggtcg 16620 tatgcggctg gagggtcgcg gacggagggt ccctgggggt cgcaacgtag gcggggcttc 16680 tgtggtgatg cggagagggg gcggcccgag tctgcctggc tgctgcgtct cgctccgagt 16740 gccgaggtgc aaatgcgacc agactgtcgg gccagggcta acttataccc cacgcctttc 16800 ccctccccaa aggggcggca gtgacgattc ccccaatggc cgcgcgtccc aggggaggca 16860 ggcccaccgc ggggcggccc cgtccccggg gaccaacccg gcgcccccaa agaatatcat 16920 tagcatgcac ggcccggccc ccgatttggg ggcccaaccc ggtgtccccc aaagaacccc 16980 attagcatgc ccctcccgcc gacgcaacag gggcttggcc tgcgtcggtg ccccggggct 17040 tcccgccttc ccgaagaaac tcattaccat acccggaacc ccaggggacc aatgcgggtt 17100 cattgagcga cccgcgggcc aatgcgcgag gggccgtgtg ttccgccaaa aaagcaatta 17160 gcataacccg gaaccccagg ggagtggtta cgcgcggcgc gggaggcggg gaataccggg 17220 gttgcccatt aagggccgcg ggaattgccg gaagcgggaa gggcggccgg ggccgcccat 17280 taatgagttt ctaattacca taccgggaag cggaacaagg cctcttgcaa gtttttaatt 17340 accataccgg gaagtgggcg gcccggccca ttgggcggta actcccgccc aatgggccgg 17400 gccccgaaga ctcggcggac gctggttggc cgggccccgc cgcgctggcg gccgccgatt 17460 ggccagtccc gcccccgagg cggcccgccc tgtgagggcg ggctggctcc aagcgtatat 17520 atgcgcggct cctgccatcg tctctccgga gagcggcttg gtgcggagct cccgggagct 17580 ccgcggaaga cccaggccgc ctcgggtgta acgttagacc gagttcgccg ggccggctcc 17640 gcgggccagg gcccgggcac gggcctcggg ccccaggcac ggcccgatga ccgcctcggc 17700 ctccgccacc cggcgccgga accgagcccg gtcggcccgc tcgcgggccc acgagccgcg 17760 gcgcgccagg cgggcggccg aggcccagac caccaggtgg cgcacccgga cgtggggcga 17820 gaagcgcacc cgcgcggggg tcgcgggggt cgcgggggtc gcgggggtcg cgggggtcgc 17880 ggggggctcc ggcgccccct ccccgcccgc gcgtcgcagg cgcaggcgcg ccaggtgctc 17940 cgcggtgacg cgcaggcgga gggcgaggcg cggcggaagg cggaaggggc gcgagggggg 18000 gtgggagggg tcagccccgc cccccgggcc cacgccgggc ggtgggggcc cggggggcgg 18060 ggggcggcgg cggtgggccg ggcctctggc gccgactcgg gcggggggct gtccggccag 18120 tcgtcgtcat cgtcgtcgtc ggacgcggac tcgggaacgt ggagccactg gcgcagcagc 18180 agcgaacaag aaggcggggg cccaccggcg gggggcggcg gcggggcggc cgcgggcgcg 18240 ctcctgaccg cgggttccga gttgggcgtg gaggttacct gggactgtgc ggttgggacg 18300 gcgcccgtgg gcccgggcgg ccgggggcgg cgggggccgc gatggcggcg gcggcgggcc 18360 atggagacag agagcgtgcc ggggtggtag agtttgacag gcaagcatgt gcgtgcagag 18420 gcgagtagtg cttgcctgtc taactcgcta gtctcggccg cggggggccc gggctgcccg 18480 ccgccaccgc tttaaagggc cgcgcgcgac ccccgggggg tgtgttttgg ggggggcccg 18540 ttttcggcgt ctggccgctc ctccccccgc tcctcccccc gctcctcccc ccgctcctcc 18600 ccccgctcct ccccccgctc ctccccccgc tcctcccccc gctcctcccc ccgctcctcc 18660 ccccgctcct ccccccgctc ctccccccgc tcctcccccc gctcctcccc ccgctcctcc 18720 ccccgctcct ccccccgctc ctccccccgc tcctcccccc gctcctcccc ccgctcccgc 18780 ggccccgccc cccacgcccg ccgcgcgcgc gcacgccgcc cggaccgccg cccgcctttt 18840 ttgcgcgcgc gcgcgcccgc ggggggcccg ggctgccaca ggtgaaacca acagagcacg 18900 gcgcactccg cacgtcacac gtcacgtcat ccaccacacc tgcccaacaa cacaactcac 18960 agcgacaact caccgcgcaa caactcctgt tcctcatcca cacgtcaccg cgcacctccc 19020 gctcctccag acgtaccccg gcgcaacaca ccgctcctgc tacacaccac cgccccctcc 19080 ccagccccag ccctccccag ccccagccct ccccggcccc agccctcccc ggccccagcc 19140 ctccccggcc ccagccctcc ccggccccag ccctccccgg ccccagccct ccccggcccc 19200 agccctcccc ggcgcgtccc gcgctccctc gggggggttc gggcatctct acctcagtgc 19260 cgccaatctc aggtcagaga tccaaaccct ccgggggcgc ccgcgcacca ccaccgcccc 19320 tcgccccctc ccgcccctcg ccccctcccg cccctcgccc cctcccgccc ctcgccccct 19380 cccgcccctc gccccctccc gcccctcgcc ccctcccgcc cctcgccccc tcccgcccct 19440 cgccccctcc cgcccctcgc cccctcccgc ccctcgcccc ctcccgcccc tcgccccctc 19500 ccgcccctcg ccccctcccg cccctcgccc cctcccgccc ctcgccccct cccgcccctc 19560 gccccctccc gcccctcgcc ccctcccgcc cctcgccccc tcccgcccct cgccccctcc 19620 cgcccctcgc cccctcccgc ccctcgaata aacaacgcta ctgcaaaact taatcaggtt 19680 gttgccgttt attgcgtctt cgggtctcac aagcgccccg ccccgtcccg gcccgttaca 19740 gcaccccgtc cccctcgaac gcgccgccgt cgtcttcgtc ccaggcgcct tcccagtcca 19800 caacttcccg ccgcgggggc gtggccaagc ccgcctccgc ccccagcacc tccacggccc 19860 ccgccgccgc cagcacggtg ccgctgcggc ccgtggccga ggcccagcga atcccgggcg 19920 gcgccggcgg cagggccccc gggccgtcgt cgtcgccgcg cagcaccagc gggggggcgt 19980 cgtcgtcggg ctccagcagg gcgcgggcgc aaaagtccct ccgcggcccg cgccaccggg 20040 ccgggccggc gcgcaccgcc tcgcgcccca gcgccacgta cacgggccgc agcggcgcgc 20100 ccaggcccca gcgcgcgcag gcggcgtgcg agtgggcctc ctcctcgcag aagtccggcg 20160 cgccgggcgc catggcgtcg gtggtccccg aggccgccgc ccggccgtcc agcgccggca 20220 gcacggcccg gcggtactcg cgcggggaca tgggcaccgg cgtgtccggg ccgaagcgcg 20280 tgcgcacgcg gtagcgcacg ttgccgccgc ggcacaggcg cagcggcggc gcgtcggggt 20340 acaggcgcgc gtgcgcggcc tccacgcgcg cgaagacccc cgggccgaac acgcggcccg 20400 aggccagcac cgtgcggcgc aggtcccgcg ccgccggcca gcgcacggcg cactgcacgg 20460 cgggcagcag ctcgcacgcc aggtaggcgt gctgccgcga caccgcgggc ccgtcggcgg 20520 gccagtcgca ggcgcgcacg gtgttgacca cgatgagccg ccggtcgccg gcgctggcga 20580 gcagccccag aaactccacg gccccggcga aggccaggtc ccgcgtggac agcagcagca 20640 cgccctgtgc gcccagcgcc gacacgtcgg gggcgccggt ccaattgccc gcccaggcgg 20700 ccgtgtccgg cccgcacagc cggttggcca gggccgccag caggcaggac agcccgccgc 20760 gctcggcgga ccactccggc ggcccccccg aggccccgcc gccggccagg tcctcgcccg 20820 gcagcggcga gtacagcacc accacgcgca cgtcctcggg gtcggggatc tggcgcatcc 20880 aggccgccat gcggcgcagc gggcccgagg cgcgcagggg gccaaagagg cggcccccgg 20940 cggccccgtg ggggtggggg ttatcgtcgt cgtcgccgcc gccgcacgcg gcctgggcgg 21000 cgggggcggg cccggcgcac cgcgcggcga tcgaggccag ggcccgcggg tcaaacatga 21060 gggccggtcg ccaggggacg gggaacagcg ggtggtccgt gagctcggcc acggcgcgcg 21120 gggagcagta ggcctccagg gcggcggccg cgggcgccgc cgtgtggctg ggccccgggg 21180 gctgccgccg ccagccgccc agggggtcgg ggccctcggc gggccggcgc gacacggcca 21240 cggggcgcgg gcgggcctgc gccgcggcgg cccggggcgc cgcgggctgg gcgggggcgg 21300 gctcgggccc cgggggcgtg gaggggggcg cgggcgcggg gaggggggcg cgggcgtccg 21360 agccgggggc gtccgcgccg ctcttcttcg tcttcggggg tcgcgggccg ccgcctccgg 21420 gcggccgggc cgggccggga ctcttgcgct tgcgcccctc ccgcggcgcg gcggaggcgg 21480 cggcggccgc cagcgcgtcg gcggcgtccg gtgcgctggc cgccgccgcc agcagggggc 21540 gcaggctctg gttgtcaaac agcaggtccg cggcggcggc ggccgcggag ctcggcaggc 21600 gcgggtcccg cggcagcgcg gggcccaggg ccccggcgac caggctcacg gcgcgcacgg 21660 cggccacggc ggcctcgctg ccgccggcca cgcgcaggtc cccgcgcagg cgcatgagca 21720 ccagcgcgtc gcgcacgaac cgcagctcgc gcagccacgc gcgcaggcgg ggcgcgtcgg 21780 cgtgcggcgg cggcggggaa gcggggcccg cgggtccctc cggccgcggg gggctggcgg 21840 gccgggcccc ggccagcccc gggacggccg ccaggtcgcc gtcgaagccc tcggccagcg 21900 cctccaggat cccgcggcag gcggccaggc actcgacggc cacgcggccg gcctgggcgc 21960 ggcgcccggc gtcgtcgtcg gcgtcggcgt ggcgggcggc gtcggggtcg tcgccccccg 22020 cgggggaggc gggcgcggcg gacagccgcc ccagggcggc gaggatcccc gcggcgccgt 22080 acccggcggg caccgcgcgc tcgcccggtg cggcggcggc gacggcggcg accccctcgt 22140 catctgcgcc ggcgccgggg ctccccgcgg cccccgtcag cgccgcgttc tcgcgcgcca 22200 acaggggcgc gtaggcgcgg cgcaggctgg tcagcaggaa gcccttctgc gcgcggtcgt 22260 atcggcggct catggccacg gcggccgccg cgtgcgccag gccccagccg aagcggccgg 22320 ccgccatggc gtagcccagg tggggcacgg cccgcgccac gctgccggtg atgaaggagc 22380 tgctgttgcg cgcggcgccc gagatccgga agcaggcctg gtccagcgcc acgtccccgg 22440 ggaccacgcg cgggttctgg agccacccca tggcctccgc gtccggggtg tacagcagcc 22500 <212> Type: DNA ...

SequenceName：cos48

SequenceDescription: Sequence Name: cos48 Seq10: [Electronic version File name: cos56 (Seq10). WorkFile] SequenceName: cos56 Sequence -------- <213> OrganismName: Human herpes simplex virus type 1 <400> PreSequenceString: gggggcccac gccgacgcag ggctccccca ggcccgcgat ctcgccccgc agggggtgcg 60 tgatggccac gcgccgttcg ctgaacgctt cgtcctgcag gtaagtctcg ctggccccgt 120 aaagatgcag agccgcggcc gtcaagtccg caggagccgc gggttccggg cccgacggca 180 cgaaaaacac catggctccc gcccaccgta cgtccgggcg atcgcgggtg taatacgtca 240 ggtatggata catgtccccc gcccgcactt tggcgatgaa cgcgggggtg ccctccggaa 300 ggccgtgcgg gtcaaaaagg tatgcggtgt cgccgtccct gaacagcccc atccctaggg 360 ggccaatggt taggagcgtg tacgacaggg ggcgcagggc ccacgggccg gcgaagaacg 420 tgtgtgcggg gcattgtgtc tccagcaggc ccgccgcggg ctccccgaag aagcccacct 480 cgccgtatac gcgcgagaag acacagcgca gtccgccgcg cgcccctggg tactcgagga 540 agttggggag ctcgacgatc gaacacatgc gcggcggccc agggcccgcg gtcgcgcgcg 600 tccactcgcc cccctcgacc aaacatccct cgatggcctc cgcggacagg acgtcgcgag 660 ggcccacatc aaatatgagg ctgagaaagg acagcgacga gcgcatgcac gataccgacc 720 cccccggctc caggtcgggc gcgaactggt tccgagcacc ggtgaccacg atgtcgcgat 780 cccccccgcg ttccatcgtg gagtgcggtg gggtgcccgc gatcatatgt gccctgctgg 840 ccagagaccc ggcctgttta tggaccggac ccccggggtt agtgttgttt ccgccaccca 900 tgcccccgta ccatggcccc ggttcccctg attaggctac gagtcgcggt gatcgcttcc 960 caaaaaccga gctgcgtttg tctgtcttgg tcttccaccc ccccccccgc ccgcccgcac 1020 accataacac cgagaacaac acacgggggt gggcgtaaca taataaagct ttattggtaa 1080 ctagttaacg gcaagtccgt gggtggcgcg acggtgtcct ccgggatcat ctcgtcgtcc 1140 tcgacggggg tgttggaatg aggcgccccc tcgcggtccg cctggcgtgg gccgtgccca 1200 taggcctccg gcttctgtgc gtccatgggc ataggcgcgg ggagactgtt tccggcgtcg 1260 cggacctcca ggtccctggg agactccggt ccggctaacg gacgaaacgc ggaagcgcga 1320 aacacgccgt cggtgacccg caggagctcg ttcatcagta accaatccat actcagcgta 1380 acggccagcc cctggcgaga cagatccacg gagtccggaa ccgcggtcgt ctggcccagg 1440 gggccgaggc tgtagtcccc ccaggcccct aggtcgcgac ggctcgtaag cacgacgcgg 1500 tcggccgcgg ggctttgcgg gggggcgtcc tcgggcgcat gcgccattac ctctcggatg 1560 gccgcggcgc gctggtcggc cgagctgacc aagggcgcca cgaccacggc gcgctccgtc 1620 tgcaggccct tccacgtgtc gtggagttcc tggacaaact cggccacggg ctcgggtccc 1680 gcggccgcgc gcgcggcttg atagcaggcc gacagacgcc gccagcgcgc tagaaactga 1740 cccatggagc aaaacccggg gacctggtct cccgacagca gcttcgacgc ccgggcgtga 1800 atgccggaca cgacggacag aaacccgtga atttcgcgcc ggaccacggc cagcacgttg 1860 tcctcgtgcg acacctgggc cgccagctcg tcgcacaccc ccaggtgcgc cgtggtttcg 1920 gtgatgacgg aacgcaggct cgcgagggac gcgaccagcg cgcgcttggc gtcgtgatac 1980 atgctgcagt actgactcac cgcgtccccc atggcctcgg ggggccaggg ccccaggcgg 2040 tcgggcgtgt ccccgaccac cgcatacagg cggcgcccgt cgctctcgaa ccgacactcg 2100 aaaaaggcgg agagcgtgcg catgtgcagc cgcagcagca cgatggcgtc ctccagttgg 2160 cgaatcaggg ggtctgcgcg ctcggcgagg tcctgcagca ccccccgggc ggccagggcg 2220 tacatgctaa tcaacaggag gctggtgccc acctcggggg gcgggggggg ctgcagctgg 2280 accaggggcc gcagctgctc gacggcaccc ctggagatca cgtacagctc ccggagcagc 2340 tgctctatgt tgtcggccat ctgcatagtg gggccgaggc cgccccgggc ggccggttcg 2400 aggagggtga tcagcgcgcc cagtttggtg cgatggccct caaccgtggg gagatagccc 2460 agcccaaagt cccgggccca ggccaacaca cgcagggcga actcgaccgg gcggggaagg 2520 taggccgcgc tacacgtggc cctcagcgcg tccccgacca ccagggccag aacgtagggg 2580 acgaagcccg ggtctgcgag gacgttgggg tgaatgccct cgagggcggg gaagcggatc 2640 tgggtcgccg cggccaggtg gacagagggg gcgtggctgg gctgcccgac ggggagaagc 2700 gcggacagcg gcgtggccgg ggtggtgggg gtgatgtccc agtgggtctg accatacacg 2760 tcgatccaga tgagcgccgt ctcgcggaga aggctgggtt gaccggaact aaagcggcgc 2820 tcggccgtct caaactcccc cacgagcgcc cgccgcaggc tcgccagatg ttccgtcggc 2880 acggccggac ccatgatacg cgccagcgtc tggcttagaa cgccccccga caggccgacc 2940 gcctcgcaga gccgcccgtg cgtgtgctcg ctggcgccct ggacccgcct gaaagttttt 3000 acgtagttgg catagtaccc gtattcccgc gccaacccaa acacgttcga ccccgcgagg 3060 gcaatgcacc caaagagctg ctggacttcg ccgagtccgt ggccggtggg cgtccgcgcg 3120 gggacgcccg ccgccagaaa cccctccagg gccgaaaggt agtgcgtgca gtgcgagggc 3180 gtgaacccag cgtcgatcag ggtgttgatc accacggagg gcgaattggt attctggatc 3240 aacgtccacg tctgctgcag cagagccagc agccgctgct gggcgccggc ggagggctgc 3300 tccccgagct gcagcaggct ggagacggca ggctggaaga ctgccagtgc cgacgaactc 3360 aggaacggca cgtcgggatc aaacacggcc acgtccgtcc gcacgcgcgc cattagcgtc 3420 cccgggggcg cacaggccga gcgcgggctg acgcggctga gggccgtcga cacgcgcacc 3480 tcctcgcggc tgcgaaccat cttgttggcc tcgagcggcg gaatcattat ggccgggtcg 3540 atctcccgca cggtgtgctg aaactgcgcc aacaggggcg gcgggaccac agccccccgc 3600 tcgggggtcg tcaggtactc gtccaccagg gccaacgtaa agagggcccg tgtgagggga 3660 gtgagggtcg cgtcgtctat gcgctggagg tgcgccgaga acagcgtcac ccgattactc 3720 accagggcca agaaccggag gccctcttgc acgaacgggg cggggaagag caggctgtac 3780 gccggggtgg taaggttcgc gctgggctgc cccaacggga ccggcgccat cttgagcgac 3840 gtctccccaa gggcctcgat ggaggtccgc gggctcatgg ccaagcagct cttggtgacg 3900 gtttgccagc ggtctatcca ctccacggcg cactggcgga cgcggaccgg ccccagggcc 3960 gccgcggtgc gcaggccggc ggaatccagc gcatgggacg tgtcggagcc ggtgaccgcg 4020 aggatggtgt ccttgatgac ctccatctcc cggaaggcct ggtcgggggc ctcggggaga 4080 gccaccacca agcggtgtac gagcaacccg gggaggttct cggccaagag cgccgtctcc 4140 ggaagcccgt gggcccggtg gagcgcgcac aggtgttcca gcagcggccg ccagcagtcc 4200 cgcgcgtctg ccggggcgat ggccgttccc gacaacagaa acgccgccat ggcggcgcgc 4260 agcttggccg tggccagaaa cgccgggtcg tccgccccgt ttgccgtctc ggccgtgggg 4320 gttggcggtt ggcgaaggcc ggctaggctc gccaataggc gctgcatagg tccgtccgag 4380 ggcggaccgg cgggtgaggt cgtgacgacg ggggcctcgg acgggagacc gcggtctgcc 4440 atgacgcccg gctcgcgtgg gtgggggaca gcgtagacca acgacgagac cgggcgggaa 4500 tgactgtcgt gcgctgtagg gagcggcgaa ttatcgatcc cccgcggccc tccaggaccc 4560 ccgcaggcgt tgcgagtacc ccgcgtcttc gcggggtgtt atacggccac ttaagtcccg 4620 gcatcccgtt cgcggaccca ggcccggggg attgtccgga tgtgcgggca gcccggacgg 4680 cgtgggttgc ggactttctg cggggcggcc caaatggccc tttaaacgtg tgtatacgga 4740 cgcgccgggc cagtcggcca acacaaccca ccggaggcgg tagccgcgtt tggctgtggg 4800 gtgggtggtt ccgccttgcg tgagtgtcct ttcgaccccc ccccccctcc ctcccccggg 4860 tcttgctagg tcgcgatctg gggtcgcaat gaagaccaat ccgctacccg caaccccttc 4920 cgtgtggggc gggagtaccg tggaactccc ccccacaaca cgcgataccg cgggacaggg 4980 cctgcttcgg cgcgtcctgc gccccccgat ctctcgccgc gacggcccag ggctccccag 5040 ggggtcggga ccccggaggg cggccagcac gctgtggttg cttggcctgg acggcacaga 5100 cgcgccccct ggggcgctga cccccaacga cgataccgaa caggccctgg acaagatcct 5160 gcggggcacc atgcgcgggg gggcggccct gatcggctcc ccgcgccatc atctaacccg 5220 ccaagtgatc ctgacggatc tgtgccaacc caacgcggat cgtgctggga cgctgcttct 5280 ggcgctgcgg caccccgccg acctgcctca cctggcccac cagcgcgccc cgccaggccg 5340 gcagaccgag cggctgggcg aggcctgggg ccagctgatg gaggcgaccg ccctggggtc 5400 ggggcgagcc gagagcgggt gcacgcgcgc gggcctagtg tcgtttaact tcctggtggc 5460 ggcgtgtgcc gcctcgtacg acgcgcgcga cgccgccgat gcggtacggg cccacgtcac 5520 ggccaactac cgcgggacgc gggtgggggc gcgcctggat cgtttttccg agtgtctgcg 5580 cgccatggtt cacacgcacg tcttccccca cgaggtcatg cggtttttcg gggggctggt 5640 gtcgtgggtc acccaggacg agctagcgag cgtcaccgcc gtgtgcgccg ggccccagga 5700 ggcggcgcac accggccacc cgggccggcc ccgctcggcc gtgatcctcc cggcatgtgc 5760 gttcgtggac ctggacgccg agctggggct ggggggcccg ggcgcggcgt ttctgtacct 5820 ggtattcact taccgccagc gccgggacca ggagctgtgt tgtgtgtacg tgatcaagag 5880 ccagctcccc ccgcgcgggt tggagccggc cctggagcgg ctgtttgggc gcctccggat 5940 caccaacacg attcacggca ccgaggacat gacgcccccg gccccaaacc gaaaccccga 6000 cttccccctc gcgggcctgg ccgccaatcc ccaaaccccg cgttgctcgg ctggccaggt 6060 cacgaacccc cagttcgccg acaggctgta ccgctggcag ccggacctgc gggggcgccc 6120 caccgcacgc acctgtacgt acgccgcctt tgcagagctc ggcatgatgc ccgaggatag 6180 tccccgctgc ctgcaccgca ccgagcgctt tggggcggtc agcgtccccg ttgtcattct 6240 ggaaggcgtg gtgtggcgcc ccggcgagtg gcgggcatgc gcgtgagcgt agcaaacgcc 6300 ccgcccacac aacgctccgc ccccaacccc ttccccgctg tcactcgttg ttcgttgacc 6360 cgggcgtccg ccaaataaag ccactgaaac ccgaaacgcg agtgttgtaa cgtcctttgg 6420 gcgggaggaa gccacaaaat gcaaatggga tacatggaag gaacacaccc ccgtgactca 6480 ggacatcggt gtgtcctttt gggtttcact gaaactggcc cgcgccccac ccctgcgcga 6540 tgtggataaa aagccagcgc gggtggttta gggtaccaca ggtgggtgct ttggaaactt 6600 gccggtcgcc gtgctcctgt gagcttgcgt ccctccccgg tttcctttgc gctcccgcct 6660 tccggacctg ctctcgccta ctcttctttg gctctcggtg cgattcgtca ggcagcggcc 6720 ttgtcgaatc tcgaccccac cactcgccgg acccgccgac gtcccctctc gagcccgccg 6780 aaacccgccg cgtctgttga aatggccagc cgcccagccg catcctctcc cgtcgaagcg 6840 cgggccccgg ttgggggaca ggaggccggc ggccccagcg cagccaccca gggggaggcc 6900 gccggggccc ctctcgccca cggccaccac gtgtactgcc agcgagtcaa tggcgtgatg 6960 gtgctttccg acaagacgcc cgggtccgcg tcctaccgca tcagcgataa caactttgtc 7020 caatgtggtt ccaactgcac catgatcatc gacggagacg tggtgcgcgg gcgcccccag 7080 gacccggggg ccgcggcatc ccccgctccc ttcgttgcgg tgacaaacat cggagccggc 7140 agcgacggcg ggaccgccgt cgtggcattc gggggaaccc cacgtcgctc ggcggggacg 7200 tctaccggta cccagacggc cgacgtcccc accgaggccc ttgggggccc ccctcctcct 7260 ccccgcttca ccctgggtgg cggctgttgt tcctgtcgcg acacacggcg ccgctctgcg 7320 gtattcgggg gggaggggga tccagtcggc cccgcggagt tcgtctcgga cgaccggtcg 7380 tccgattccg actcggatga ctcggaggac acggactcgg agacgctgtc acacgcctcc 7440 tcggacgtgt ccggcggggc cacgtacgac gacgcccttg actccgattc gtcatcggat 7500 gactccctgc agatagatgg ccccgtgtgt cgcccgtgga gcaatgacac cgcgcccctg 7560 gatgtttgcc ccgggacccc cggcccgggc gccgacgccg gtggtccctc agcggtagac 7620 ccacacgcgc cgacgccaga ggccggcgct ggtcttgcgg ccgatcccgc cgtggcccgg 7680 gacgacgcgg aggggctttc ggacccccgg ccacgtctgg gaacgggcac ggcctacccc 7740 gtccccctgg aactcacgcc cgagaacgcg gaggccgtgg cgcgctttct gggagatgcc 7800 gtgaaccgcg aacccgcgct catgctggag tacttttgcc ggtgcgcccg cgaggaaacc 7860 aagcgtgtcc cccccaggac attcggcagc ccccctcgcc tcacggagga cgactttggg 7920 cttctcaact acgcgctcgt ggagatgcag cgcctgtgtc tggacgttcc tccggtcccg 7980 ccgaacgcat acatgcccta ttatctcagg gagtatgtga cgcggctggt caacgggttc 8040 aagccgctgg tgagccggtc cgctcgcctt taccgcatcc tgggggttct ggtgcacctg 8100 cggatccgga cccgggaggc ctcctttgag gagtggctgc gatccaagga agtggccctg 8160 gattttggcc tgacggaaag gcttcgcgag cacgaagccc agctggtgat cctggcccag 8220 gctctggacc attacgactg tctgatccac agcacaccgc acacgctggt cgagcggggg 8280 ctgcaatcgg ccctgaagta tgaggagttt tacctaaagc gttttggcgg gcactacatg 8340 gagtccgtct tccagatgta cacccgcatc gccggctttt tggcctgccg ggccacgcgc 8400 ggcatgcgcc acatcgccct ggggcgagag gggtcgtggt gggaaatgtt caagttcttt 8460 ttccaccgcc tctacgacca ccagatcgta ccgtcgaccc ccgccatgct gaacctgggg 8520 acccgcaact actacacctc cagctgctac ctggtaaacc cccaggccac cacaaacaag 8580 gcgaccctgc gggccatcac cagcaacgtc agtgccatcc tcgcccgcaa cgggggcatc 8640 gggctatgcg tgcaggcgtt taacgactcc ggccccggga ccgccagcgt catgcccgcc 8700 ctcaaggtcc ttgactcgct ggtggcggcg cacaacaaag agagcgcgcg tccgaccggc 8760 gcgtgcgtgt acctggagcc gtggcacacc gacgtgcggg ccgtgctccg gatgaagggg 8820 gtcctcgccg gcgaagaggc ccagcgctgc gacaatatct tcagcgccct ctggatgcca 8880 gacctgtttt tcaagcgcct gattcgccac ctggacggcg agaagaacgt cacatggacc 8940 ctgttcgacc gggacaccag catgtcgctc gccgactttc acggggagga gttcgagaag 9000 ctctaccagc acctcgaggt catggggttc ggcgagcaga tacccatcca ggagctggcc 9060 tatggcattg tgcgcagtgc ggccacgacc gggagcccct tcgtcatgtt caaagacgcg 9120 gtgaaccgcc actacatcta cgacacccag ggggcggcca tcgccggctc caacctctgc 9180 accgagatcg tccatccggc ctccaagcga tccagtgggg tctgcaacct gggaagcgtg 9240 aatctggccc gatgcgtctc caggcagacg tttgactttg ggcggctccg cgacgccgtg 9300 caggcgtgcg tgctgatggt gaacatcatg atcgacagca cgctacaacc cacgccccag 9360 tgcacccgcg gcaacgacaa cctgcggtcc atgggaatcg gcatgcaggg cctgcacacg 9420 gcctgcctga agctggggct ggatctggag tctgccgaat ttcaggacct gaacaaacac 9480 atcgccgagg tgatgctgct gtcggcgatg aagaccagca acgcgctgtg cgttcgcggg 9540 gcccgtccct tcaaccactt taagcgcagc atgtatcgcg ccggccgctt tcactgggag 9600 cgctttccgg acgcccggcc gcggtacgag ggcgagtggg agatgctacg ccagagcatg 9660 atgaaacacg gcctgcgcaa cagccagttt gtcgcgctga tgcccaccgc cgcctcggcg 9720 cagatctcgg acgtcagcga gggctttgcc cccctgttca ccaacctgtt cagcaaggtg 9780 acccgggacg gcgagacgct gcgccccaac acgctcctgc taaaggaact ggaacgcacg 9840 tttagcggga agcgcctcct ggaggtgatg gacagtctcg acgccaagca gtggtccgtg 9900 gcgcaggcgc tcccgtgcct ggagcccacc caccccctcc ggcgattcaa gaccgcgttt 9960 gactacgacc agaagttgct gatcgacctg tgtgcggacc gcgcccccta cgtcgaccat 10020 agccaatcca tgaccctgta tgtcacggag aaggcggacg ggaccctccc agcctccacc 10080 ctggtccgcc ttctggtcca cgcatataag cgcggactaa aaacagggat gtactactgc 10140 aaggttcgca aggcgaccaa cagcggggtc tttggcggcg acgacaacat tgtctgcatg 10200 agctgcgcgc tgtgaccgac aaaccccctc cgcgccaggc ccgccgccac tgtcgtcgcc 10260 gtcccacgct ctcccctgct gccatggatt ccgcggcccc agccctctcc cccgctctga 10320 cggcccttac ggaccagagc gcgacggcgg acctggcgat ccagattcca aagtgccccg 10380 accccgagag gtacttctac acctcccagt gtcccgacat taaccacctg cgctccctca 10440 gcatccttaa ccgctggctg gaaaccgagc ttgttttcgt gggggacgag gaggacgtct 10500 ccaagctttc cgagggcgag ctcagctttt accgcttcct cttcgctttc ctgtcggccg 10560 ccgacgacct ggttacggaa aacctgggcg gcctctccgg cctgtttgag cagaaggaca 10620 ttctccacta ctacgtggag caggaatgca tcgaagtcgt acactcgcgc gtgtacaaca 10680 tcatccagct ggtgcttttc cacaacaacg accaggcgcg ccgcgagtac gtggccggta 10740 ccatcaacca cccggccatc cgcgccaagg tggactggtt ggaagcgcgg gtgcgggaat 10800 gcgcctccgt tccggaaaag ttcattctca tgatcctcat cgagggcatc ttttttgccg 10860 cctcgtttgc cgccatcgcc taccttcgca ccaacaacct tctgcgggtc acctgccagt 10920 caaacgacct catcagccgg gacgaggccg tgcacacgac ggcctcgtgt tacatctaca 10980 acaactacct cggcgggcac gccaagcccc cgcccgaccg cgtgtacggg ctgttccgcc 11040 aggcggtcga gatcgagatc ggatttatcc gatcccaggc gccgacggac agccatatcc 11100 tgagcccggc ggcgctggcg gccatcgaaa actacgtgcg attcagcgcg gatcgcctgt 11160 tgggccttat ccacatgaag ccactgtttt ccgccccacc ccccgacgcc agctttccgc 11220 tgagcctcat gtccaccgac aaacacacca attttttcga gtgtcgcagc acctcctacg 11280 ccggggcggt cgtcaacgat ctgtgagtgt cgcggcgcgc ttctacccgt gtttgcccat 11340 aataaacctc tgaaccaaac tttgggtctc attgtgattc ttgtcaggga cgcgggggtg 11400 ggagaggata aaaggcggcg caaaaagcag taaccaggtc cgtccagatt ctgcgggcat 11460 aggataccat aattttattg gtgggtcgtt tgttcgggga caagcgcgct cgtctgacgt 11520 ttgggctact cgtcccagaa tttggccagg acgtccttgt agaacgcggg tgggggggcc 11580 tgggtccgca actgctccag aaacctgtcg gcgatatcag gggccgtgat atgccgggtc 11640 acgatagatc gcgccaggtt ttcgtcgcgg atgtcctggt agataggcag gcgtttcaga 11700 agagtccacg gcccccgctc cttggggccg ataagcgata tgacgtactt aatgtagcgg 11760 tgttccacca gctcggtgat ggtcatggga tcggggagcc agtccaggga ctctggggcg 11820 tcgtggatga cgtggcgtcg cgggttggcc acataactgc ggtgctcttc cagcagctgc 11880 gcgttcggga cctggacgag ctcgggcggg gtgagtatct ccgaggagga cgacctgggg 11940 ccggggtggc ccccggtaac gtcccgggga tccaggggga ggtcctcgtc gtcttcgtat 12000 ccgccggcga tctgttgggt tagaatttcg gtccacgaga cgcgcgtctc ggtgccgccg 12060 gcggccggcg gcagaggggg cctggtttcc gtggagcgcg agctggtgtg ttcccggcgg 12120 atggcccgcc gggtctgaga gcgactcggg ggggtccagt gacattcgcg cagcacatcc 12180 tccacggagg cgtaggtgtt attgggatgg aggtcggtgt ggcagcggac aaagagggcc 12240 aggaactggg ggtagctcat cttaaagtac tttagtatat cgcgacagtt gatcgtggga 12300 atgtagcagg cgctaatatc caacacaata tcacagccca tcaacaggag gtcagtgtcc 12360 gtggtgtaca cgtacgcgac cgtgttggtg tgatagaggt tggcgcaggc atcgtccgcc 12420 tccagctgac ccgagttaat gtaggcgtac cccagggccc ggagaacgcg aatacagaac 12480 agatgcgcca gacgcagggc cggcttcgag ggcgcggcgg acggcagcgc ggctccggac 12540 ccggccgtcc cccgggtccc cgaggccaga gaggtgccgc gccggcgcat gttggaaaag 12600 gcagagctgg gtctggagtc ggtgatgggg gaaggcggtg gagaggcgtc cacgtcactg 12660 gcctcctcgt ccgtccggca ctgggccgtc gtgcgggcca ggatggcctt ggctccaaac 12720 acaaccggct ccatacaatt gaccccgcga tcggtaacga agatggggaa aagggacttt 12780 tgggtaaaca cctttaataa gcgacagagg cagtgtagcg taatggcctc gcggtcgtaa 12840 ctggggtatc ggcgctgata tttgaccacc aacgtgtaca tgacgttcca caggtccacg 12900 gcaatggggg tgaagtaccc ggccggggcc ccaaggcccc ggcgcttgac cagatggtgt 12960 gtgtgggcaa acttcatcat cccgaacaaa cccatgtcag gtcaattgta actgcggatc 13020 ggcctaacta aggcgtggtt ggtgcgacgg tccgggacac ccgagcctgt ctctctgtgt 13080 atggtgaccc agacaacaac accgacacaa gaggacaata atccgttagg ggacgctctt 13140 tataatttcg atggcccaac tccacgcgga ttggtgcagc accctgcatg cgccggtgcg 13200 ggccaacctt ccccccgctc attgcctctt ccaaaagggt gtggcctaac gagctggggg 13260 cgtatttaat caggctagcg cggcgggcct gccgtagttt ctggctcggt gagcgacggt 13320 ccggttgctt gggtcccctg gctgccatca aaaccccacc ctcgcagcgg catacgcccc 13380 ctccgcgtcc cgcacccgag accccggccc ggctgccctc accaccgaag cccacctcgt 13440 cactgtgggg tgttcccagc ccgcgttggg atgacggatt cccctggcgg tgtggccccc 13500 gcctcccccg tggaggacgc gtcggacgcg tccctcgggc agccggagga gggggcgccc 13560 tgccaggtgg tcctgcaggg cgccgaactt aatggaatcc tacaggcgtt tgccccgctg 13620 cgcacgagcc ttctggactc gcttctggtt atgggcgacc ggggcatcct tatccataac 13680 acgatctttg gggagcaggt gttcctgccc ctggaacact cgcaattcag tcggtatcgc 13740 tggcgcggac ccacggcggc gttcctgtct ctcgtggacc agaagcgctc cctcctgagc 13800 gtgtttcgcg ccaaccagta cccggaccta cgtcgggtgg agttggcgat cacgggccag 13860 gccccgtttc gcacgctggt tcagcgcata tggacgacga cgtccgacgg cgaggccgtt 13920 gagctagcca gcgagacgct gatgaagcgc gaactgacga gctttgtggt gctggttccc 13980 cagggaaccc ccgacgttca gttgcgcctg acgaggccgc agctcaccaa ggtccttaac 14040 gcgaccgggg ccgatagtgc cacgcccacc acgttcgagc tcggggttaa cggcaaattt 14100 tccgtgttca ccacgagtac ctgcgtcacc tttgctgccc gcgaggaggg cgtgtcgtcc 14160 agcaccagca cccaggtcca gatcctgtcc aacgcgctca ccaaggcggg ccaggcggcc 14220 gccaacgcca agacggtgta cggggaaaat acccatcgca ccttctctgt ggtcgtcgac 14280 gattgcagca tgcgggcggt gctccggcga ctgcaggtcg gcgggggcac cctcaagttc 14340 ttcctcacga cccccgtccc cagtctgtgc gtcaccgcca ccggtcccaa cgcggtatcg 14400 gcggtatttc tcctgaaacc ccagaagatt tgcctggact ggctgggtca tagccagggg 14460 tctccttcag ccgggagctc ggcctcccgg gcctctggga gcgagccaac agacagccag 14520 gactccgcgt cggacgcggt cagccacggc gatccggaag acctcgatgg cgctgcccgg 14580 gcgggagagg cgggggcctt gcatgcctgt ccgatgccgt cgtcgaccac gcgggtcact 14640 cccacgacca agcgggggcg ctcggggggc gaggatgcgc gcgcggacac ggccctaaag 14700 aaacctaaga cggggtcgcc caccgcaccc ccgcccgcag atccagtccc cctggacacg 14760 gaggacgact ccgatgcggc ggacgggacg gcggcccgtc ccgccgctcc agacgcccgg 14820 agcggaagcc gttacgcgtg ttactttcgc gacctcccga ccggagaagc aagccccggc 14880 gccttctccg ccttccgggg gggcccccaa accccgtatg gttttggatt cccctgacgg 14940 ggcggggcct tggcggccgc ccaactctcg caccatcccg ggttaatgta aataaacttg 15000 gtattgccca acactttccc gcgtgtcgcg tgtggttcat gtgtgtgcct ggcgccccca 15060 ccctcgggtt cgtgtatttc ctttccctgt ccttataaaa gccgtatgtg gggcgtgacg 15120 gaaccacccc gcgtgccatc acggccaagg cgcgggatgc tccgcaacga cagccaccgg 15180 gccgtgtccc cggaggacgg ccagggacgg gtcgacgacg gacggccaca cctcgcgtgc 15240 gtgggggccc tggcgcgggg gttcatgcat atctggcttc aggccgccac gctgggtttt 15300 gcgggatcgg tcgttatgtc gcgcgggccg tacgcgaatg ccgcgtctgg ggcgttcgcc 15360 gtcgggtgcg ccgtgctggg ctttatgcgc gcaccccctc ccctcgcgcg gcccaccgcg 15420 cggatatacg cctggctcaa actggcggcc ggtggagcgg cccttgttct gtggagtctc 15480 ggggagcccg gcacgcagcc gggggccccg gccccgggcc cggccaccca gtgcctggca 15540 ctgggcgccg cctatgcggc gctcctggtg ctcgccgatg acgtctatcc gctctttctc 15600 ctcgccccgg ggcccctgtt cgtcggcacc ctggggatgg tcgtcggcgg gctgacgatc 15660 ggaggcagcg cgcgctactg gtggatcggt gggcccgccg cggccgccct ggccgcggcg 15720 gtgttggcgg gcccgggggc gaccaccgcc agggactgct tttccagggc ttgccccgac 15780 caccgccgcg tctgtgtcat caccgcaggc gagtctcttt cccgccgccc cccggaggac 15840 ccagagcgac ccggggttcc cgggcccccg tcccccccga ccccccaacg atcccacggg 15900 ccgccggccg atgaggtcgc accggccagg gtcgcgcggc ccgaaaacgt ctgggtgccc 15960 gtggtcacct ttctgggggc gggcgcgctt gccgtcaaga cggtgcgaga acatgcccgg 16020 ggaacgccgg gcccgggcct gccgctgtgg ccccaggtgt ttctcggagg ccatgtggcg 16080 gtggccctga cggagctgtg tcaggcgctt ccgccctggg accttacgga cccgctgctg 16140 tttgttcacg ccggactgca ggtcatcaac ctcgggttgg tgtttcggtt ttccgaggtt 16200 gtcgtgtatg cggcgctagg gggtgccgtg tggatttcgt tggcgcaggt gctggggctc 16260 cggcgtcgcc tgcacaggaa ggaccccggg gacggggccc ggttggcggc gacgcttcgg 16320 ggcctcttct tctccgtgta cgcgctgggg tttggggtgg gggtgctgct gtgccctccg 16380 gggtcaacgg gcgggcggtc gggcgattga tatatttttc aataaaaggc attagtcccg 16440 aagaccgccg gtgtgtgatg atttcgccat aacacccaaa ccccggatgg ggcccgggta 16500 taaattccgg aaggggacac gggctaccct cactatcgag ggcgcttggt cgggaggccg 16560 catcgaacgc acacccccat ccggtggtcc gtgtggaggt cgttttcatg cccggtctcg 16620 ctttgccggg aacgctagcc gatccctcgc gagggggagg cgtcgggcat ggccccgggg 16680 cgggtgggcc ttgccgtggt cctgtggagc ctgttgtggc tcggggcggg ggtgtccggg 16740 ggctcggaaa ctgcctccac cgggcccacg atcaccgcgg gagcggtgac gaacgcgagc 16800 gaggccccca catcggggtc ccccgggtca gccgccagcc cggaggtcac ccccacatcg 16860 accccaaacc ccaacaatgt cacacaaaac aaaaccaccc ccaccgagcc ggccagcccc 16920 ccaacaaccc ccaagcccac ctccacgccc aaaagccccc ccacgtccac ccccgacccc 16980 aaacccaaga acaacaccac ccccgccaag tcgggccgcc ccactaaacc ccccgggccc 17040 gtgtggtgcg accgccgcga cccattggcc cggtacggct cgcgggtgca gatccgatgc 17100 cggtttcgga attccacccg catggagttc cgcctccaga tatggcgtta ctccatgggt 17160 ccgtcccccc caatcgctcc ggctcccgac ctagaggagg tcctgacgaa catcaccgcc 17220 ccacccgggg gactcctggt gtacgacagc gcccccaacc taacggaccc ccacgtgctc 17280 tgggcggagg gggccggccc gggcgccgac cctccgttgt attctgtcac cgggccgctg 17340 ccgacccagc ggctgattat cggcgaggtg acgcccgcga cccagggaat gtattacttg 17400 gcctggggcc ggatggacag cccgcacgag tacgggacgt gggtgcgcgt ccgcatgttc 17460 cgccccccgt ctctgaccct ccagccccac gcggtgatgg agggtcagcc gttcaaggcg 17520 acgtgcacgg ccgccgccta ctacccgcgt aaccccgtgg agtttgtctg gttcgaggac 17580 gaccaccagg tgtttaaccc gggccagatc gacacgcaga cgcacgagca ccccgacggg 17640 ttcaccacag tctctaccgt gacctccgag gctgtcggcg gccaggtccc cccgcggacc 17700 ttcacctgcc agatgacgtg gcatcgcgac tccgtgacgt tctcgcgacg caatgccacc 17760 gggctggccc tggtgctgcc gcggccaacc atcaccatgg aatttggggt ccgcattgtg 17820 gtctgcacgg ccggctgcgt ccccgagggc gtgacgtttg cctggttcct gggggacgac 17880 ccctcaccgg cggctaagtc ggccgttacg gcccaggagt cgtgcgacca ccccgggctg 17940 gctacggtcc ggtccaccct gcccatttcg tacgactaca gcgagtacat ctgtcggttg 18000 accggatatc cggccgggat tcccgttcta gaacaccacg gcagtcacca gcccccaccc 18060 agggacccca ccgagcggca ggtgatcgag gcgatcgagt gggtggggat tggaatcggg 18120 gttctcgcgg cgggggtcct ggtcgtaacg gcaatcgtgt acgtcgtccg cacatcacag 18180 tcgcggcagc gtcatcggcg gtaacgcaag acccccccgt taccttttta atatctatat 18240 agtttggtcc cccctctatc ccgcccaccg ctgggcgcta taaagccgcc accctctctt 18300 ccctcaggtc atccttggtc gatcccgaac gacacacggc gtggagcaaa acgcctcccc 18360 ctgagccgct ttcctaccaa cacaacggca tgcctctgcg ggcatcggaa cacgcctacc 18420 ggcccctggg ccccgggaca ccccccatgc gggctcggct ccccgccgcg gcctgggttg 18480 gcgtcgggac catcatcggg ggagttgtga tcattgccgc gttggtcctc gtgccctcgc 18540 gggcctcgtg ggcactttcc ccatgcgaca gcggatggca cgagttcaac ctcgggtgca 18600 tatcctggga tccgaccccc atggagcacg agcaggcggt cggcggctgt agcgccccgg 18660 cgaccctgat cccccgcgcg gctgccaaac agctggccgc cgtcgcacgc gtccagtcgg 18720 caagatcctc gggctactgg tgggtgagcg gagacggcat tcgggcctgc ctgcggctcg 18780 tcgacggcgt cggcggtatt gaccagtttt gcgaggagcc cgcccttcgc atatgctact 18840 atccccgcag tcccgggggc tttgttcagt ttgtaacttc gacccgcaac gcgctggggc 18900 tgccgtgagg cgcgtgtact gcggtctgtc tcgtctcctc ttctcccctt ccctccccct 18960 ccgcatccca ggatcacacc ggtcaacgag ggttgggggg gtccggcacg gacccaaaat 19020 aataaacaca caatcacgtg cgataaaaag aacacgcggt cccctgtggt gtttttggtt 19080 atttttatta aatctcgtcg acaaacaggg ggaaaggggc gtggtctagc gacggcagca 19140 cgggcggagg cgttcaccgg ctccggcgtc cttcgcgttt aagcttggtc aggagggcgc 19200 tcagggcggc gacgttggtc gggccgtcgt tggtcagggc gttggctcga tggcgggcga 19260 ggacgggcga ggggctcaac ggcgggggcg ggggcccggt gcggcccggg ggggaaaata 19320 gggcggatcc cccccagtcg tacaggggat tttccgcctc aatgtacggg gaggccggcg 19380 ctgcattcgc cgtgttcacg cagacgtttt cgtagacccg catccatggt atttcctcgt 19440 agacacgccc cccgtcctcg ctcaccgtct cgtatattga ctcgtcgtcc tcgtaggggg 19500 cgtgccgttc gcgggccgag gcggcgtggg tggctttgcg gcgggcgtcg tcgtcgtcgt 19560 cgtcggccgt cagatacgtg gcttccatct ggtcgggttc tccctccggg gcgggtcccc 19620 acacccgtgg ccgatcgagg ctccccagag acgcgcgccg gacgaggagg gggcacgtcg 19680 ccgccggcgg tcgcctgtcg ggtcccgcga cgttacgggc cgggaggcgc gggggcacct 19740 cccccatgtg cgtgtaatac gtggccggct gtgtggccgc agcggggggc tcggcgaccg 19800 ggtcgttcgc atccggaagc gggggccccg cgccgtccgc gcggcgcctc cggaacctcc 19860 gggtggacgc gggggtcgag tgtaggcgag gtcgggggag gggcgggggc tcgttgtcgc 19920 gccgcgcccg ctgaatcttt tcccgacagg tcccaccccc cgcgcgatgc ccccccgggc 19980 cgctggccat gtcgtccggg ggaggccccg cggaccacgt cgtccggcga gacgccacga 20040 gccgcaggat ggactcgtag tggagcgacg gcgccccgtt gcggagcaga tccgcggcca 20100 gggcggcccc gaaccaagcc ttgatgctca actccatccg ggcccagctg ggggcggtca 20160 tcgtggggaa caggggggcg gtggtccgac agaaacgctc ctggctgtcc accgcggccc 20220 gcagatactc gttgttcagg ctgtcggtgg cccagacgcc gtacccggtg agggtcgcgt 20280 tgatgatata ctgggcgtgg tgatggacga tcgacagaac ctccaccgtg gatacgacgg 20340 tatccacggt cccgtacgta ccgccgctcc gcttgccggt ctgccacagg ttggctaggc 20400 gcgtcaggtg gcccaggacg tcgctgaccg ccgccctgag cgccatgcac tgcatggagc 20460 cggtcgtgcc gctgggaccc cggtccagat ggcgcgcgaa cgtttccgcg ggcgcctccg 20520 ggctgccgcc gagcgggagg aaccggcgat tggagggact cagccggtga catacgtgct 20580 tgtccgtcgt ccacagcatc caggacgccc accggtacag cacggagacg taggccagga 20640 gctcgttgag ccgcagtgcg gtgtcggtgc tggggcggct tgggtccgcc gggcgcataa 20700 agaacatgta ctgctgaatc cgatggaggg cgtcgcgcag gccggccacg gtggcggcgt 20760 acttgccgcc acggccccgc tcttgaacgg ggtgcgcgcc agcgagcttt ggcgccaggg 20820 tgggccgcag cagcacgtga aggctggggt cgcagtcgcc cacggggtcc tcggggacgt 20880 ccaggccgct gggcaccacc gtctgcaggt acttccagta ctgcgtgagg atggcgcggc 20940 tcaactggcc gccgggcagc tccacctcgc ccagcgcctg ggtggcggcc gaagcgtagt 21000 gccggatgta ctcgtagtgc gggtcgctgg cgagcccgtc cacgatcaaa ctctcgggaa 21060 ccgtgttgtg ttgccgcgcg gccaaccgga cgctgcgatc ggtgcaggtc agaaacgccg 21120 gctgcgcgtc gtcggagcgc tgccgcaagg cgcccacggc cgcgctaagg agcccctccg 21180 gggtggggag cagacacccg ccgaagatgc gccgctcggg aacgcccgcg ttgtcgccgc 21240 ggatcaggtt ggcaggcgtc aggcaccgcg ccagccgcag ggagctcgcg ccgcgcgtcc 21300 ggcgctgcat ggtgacgccc gttcggtcgg gacccgccgg tcggagttat gccgcgtcca 21360 gggccatcgg ggcgcttttt atcgggagga gcttatgggc gtggcgggcc tcccagcccg 21420 gtcgcgcgcc tccccgacac gtgcgcccgc agggcggcgg ccccctcgtc tcccatcagc 21480 agtttcctaa actgggacat gatgtccacc acgcggaccc gcgggcccaa cacggacccg 21540 ccgcttacgg gggcgggggg gaagggctcc aggtccttga gaagaaaggc ggggtctgcc 21600 gtcccggaca cgggggcccg gggcgctgag gaggcggggc gcagatccac gtgctccgcg 21660 gccgcgcgga cgtccgccca gaacttggcg ggggtggtgc gcgcgtacag gggctgggtc 21720 gctcggagga cgcacgcgta gcgcaggggg gtgtacgtgc ccacctcggg ggccgtgaat 21780 cccccgtcaa acgcggccag tgtcacgcac gccaccacgg tgtcggcaaa gcccagcagc 21840 cgctgcagga cgagcccggc ggccagaatg gcgcgcgtgg ccgccgcgtc gtcccggcgc 21900 cggtgcgcgt ccccgcacgc ccgggcgtac tttaaggtca cggtcgccag ggccgtgtgc 21960 agcgcgtaca ccgcagcgcc cagcacggcg ttgagcccgc tgttggcgag cagccggcgc 22020 gctgcggtgt cgcccagcgc ctcgtgctcg gcccccacga ccgcggggct tcccaggggc 22080 agggcgcgaa acagctcctc ccgcgccacg tccgcaaagg cggggtggtg cacgtgcggg 22140 tgcaggcgcg cccccacgac caccgagagc cactggaccg tctgctccgc catcaccgcc 22200 agcacatcca gcacgcgccc caggaaggcg gcctcccgcg tcaaaacgca ccggacggcg 22260 tcgggattga agcgggcgag cagggccccg gtggccaggt acgtcatgcg gccggcatag 22320 cgggcggcca cgcgacagtc gcggtccagc agcgcgcgca ccccgggcca gtacagcagg 22380 gaccccagcg agctgcggaa caccgcggcg tcggggccgg attgggggga cactaacccc 22440 cccgcgctca gtaacggcac ggccgcggcc ccgacgggac gcaacgccgt gaggctcgcg 22500 aactgccgcc tcagctcggc cgccctgtcg tccaggtcag acccgcgcgc ctccgcgtga 22560 <212> Type: DNA ...

SequenceName：cos56

SequenceDescription：Custom?Codon------------Sequence?Name：cos56

Claims (13)

1. a recombinant herpes simplex virus (HSV) is characterized in that having inserted in its genome a kind of dna sequence dna, and it has the nucleotide sequence shown in the SEQ ID NO.1 or its homologous sequence.

2. a recombinant herpes simplex virus (HSV) is characterized in that having inserted in its genome a kind of dna sequence dna, and it has the nucleotide sequence shown in the SEQ ID NO.2 or its homologous sequence.

3. a recombinant herpes simplex virus (HSV) is characterized in that having inserted in its genome a kind of dna sequence dna, and it has the nucleotide sequence shown in the SEQ ID NO.3 or its homologous sequence.

4. a recombinant herpes simplex virus (HSV) is characterized in that having inserted in its genome a kind of dna sequence dna, and it has the nucleotide sequence shown in the SEQ ID NO.4 or its homologous sequence.

5. a recombinant herpes simplex virus (HSV) is characterized in that having inserted in its genome a kind of dna sequence dna, and it has the nucleotide sequence shown in the SEQ ID NO.5 or its homologous sequence.

6. recombinant herpes simplex virus as claimed in claim 1, wherein dna sequence dna SEQ ID NO.1 is inserted in the xbaI site of the genomic UL2 gene of HSV.

7. recombinant herpes simplex virus as claimed in claim 2, wherein dna sequence dna SEQ ID NO.2 is inserted in the xbaI site of the genomic UL2 gene of HSV.

8. recombinant herpes simplex virus as claimed in claim 3, wherein dna sequence dna SEQ ID NO.3 is inserted in the xbaI site of the genomic UL2 gene of HSV.

9. recombinant herpes simplex virus as claimed in claim 4, wherein dna sequence dna SEQ ID NO.4 is inserted in the xbaI site of the genomic UL2 gene of HSV.

10. recombinant herpes simplex virus as claimed in claim 5, wherein dna sequence dna SEQ ID NO.5 is inserted in the xbaI site of the genomic UL2 gene of HSV.

11. as claim 1,2,3,4,5 described recombinant herpes simplex virus, dna sequence dna SEQ IDNO.1 wherein, SEQ ID NO.2, SEQ ID NO.3, SEQ ID NO.4, or SEQ ID NO.5 is inserted into genomic other dispensable gene district of HSV.

12. the preparation method of a recombinant herpes simplex virus, this method comprises that structure contains SEQ ID NO.1, SEQID NO.2, SEQ ID NO.3, the dna fragmentation of SEQ ID NO.4 or SEQ ID NO.5, and utilize engineered method that this dna fragmentation is inserted in the genome of hsv, thereby obtain the hsv of reorganization.

13. as claim 1,2,3,4,5 described recombinant herpes simplex virus, wherein inserted IDNO.1, SEQ ID NO.2, SEQ ID NO.3, other dna sequence dna of dna fragmentation homologous of SEQ ID NO.4 or SEQ ID NO.5 with SEQ.

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