CN1461805A - Structure of recombination herpes simplex virus and its use - Google Patents
Structure of recombination herpes simplex virus and its use Download PDFInfo
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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
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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Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN100540660C (en) * | 2004-08-27 | 2009-09-16 | 上海交通大学附属儿童医院 | A kind of transgenic mice hepatopathy animal model, its preparation method and application |
CN111344412A (en) * | 2017-07-10 | 2020-06-26 | 优尼科Ip有限公司 | Means and methods for AAV gene therapy in humans |
CN112166195A (en) * | 2018-03-06 | 2021-01-01 | 佛罗里达大学研究基金会有限公司 | AAV chimeras |
-
2002
- 2002-05-27 CN CN 02117965 patent/CN1461805A/en active Pending
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN100540660C (en) * | 2004-08-27 | 2009-09-16 | 上海交通大学附属儿童医院 | A kind of transgenic mice hepatopathy animal model, its preparation method and application |
CN111344412A (en) * | 2017-07-10 | 2020-06-26 | 优尼科Ip有限公司 | Means and methods for AAV gene therapy in humans |
CN112166195A (en) * | 2018-03-06 | 2021-01-01 | 佛罗里达大学研究基金会有限公司 | AAV chimeras |
US11905524B2 (en) | 2018-03-06 | 2024-02-20 | University Of Florida Research Foundation, Incorporated | AAV chimeras |
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