CN116555335A - Adjustable pilot editor and application thereof - Google Patents

Adjustable pilot editor and application thereof Download PDF

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CN116555335A
CN116555335A CN202210114825.0A CN202210114825A CN116555335A CN 116555335 A CN116555335 A CN 116555335A CN 202210114825 A CN202210114825 A CN 202210114825A CN 116555335 A CN116555335 A CN 116555335A
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马涵慧
冯颖
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ShanghaiTech University
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Abstract

The invention belongs to the technical field of biological medicine, and discloses a gene leading editing system which comprises a vector, wherein the vector contains a gene for coding sgRNA, a gene for coding separated leading RNA (pRNA) and a gene for coding fusion protein, and the separated leading RNA comprises a reverse transcription template RTT, a main binding site PBS and an RNA stem-loop structure. The invention protects the 3 'extension from degradation by separating the 3' extension from the pegRNA and adding a different RNA aptamer to the separated 3 'extension or circularizing the 3' extension. Based on the isolated leader RNA system, we further developed an inducible leader editing tool.

Description

Adjustable pilot editor and application thereof
Technical Field
The invention belongs to the field of biological medicine, and relates to an adjustable pilot editor and application thereof, in particular to an adjustable pilot editor (prime editors), which belongs to the platform technology of gene therapy and can be used for gene therapy of diseases such as site-directed mutagenesis, insertion, screening out genome DNA fragments and the like.
Background
Human diseases are mostly closely related to genes, so targeted changes according to genes have long been a hope of life sciences. Despite the rapid progress of gene editing techniques, most diseases have problems that are difficult to correct among the genetic variations known to more than 75000 humans associated with the disease.
Insertion and deletion at specific genomic sites can be performed using engineered nucleases such as ZFPs, TALENs or CRISPR-Cas, effectively using DNA double strand breaks (double strand breaks, DSBs) mediated DNA editing. However, DSB production can lead to a number of adverse consequences such as editing non-singleness, gene sequence translocation and P53 activation.
In cells, frequent DNA double-strand breaks (DSBs) of chromatin are necessary for meiotic recombination and development of the vertebrate immune system on the one hand, and incorrect repair of DSBs can produce mutations and promote genomic instability, failing to repair DSBs can lead to cell death on the other hand. Generally, there are two main repair mechanisms activated by DSBs, one is homology-directed repair (HDR), and the other is non-homologous end joining (NHEJ). As the most predominant repair pathway for DNA double strand breaks, HDR uses homologous sequences as templates for repair to accomplish correction of gene sequences and can only occur in the G2/S phase of cells; in contrast, NHEJ does not require homologous sequences for repair to introduce insertions and deletions at genomic sites near DSBs. However, HDR mediated gene correction efficiency has been low (typically less than 5%) due to limitations in the homologous recombination mechanism itself. Thus, the transition of CRISPR/Cas gene editing tools from scientific research to application is greatly limited. The resulting Base Editor (BE) can convert C.G into T.A and A.T into G.C, and although this method can greatly improve the editing efficiency of the gene locus, the mutation mode of this method is single and requires DNA double strand break, and these methods have certain limitations for the application in precise treatment.
The pilot editing (priority editing) was invented by MIT David Liu laboratory at the end of 2019. This technique is considered to be a third generation gene editing technique based on CRISPR, and can be used to make precise site-directed mutations, insertions and deletions of small pieces of DNA at any site in the genome. The main problem of the current pilot editing is that the editing efficiency is in different cells and different sites are very different. Optimizing the efficiency of the lead editing is urgent.
Disclosure of Invention
The pilot editing (prime) can be used to screen out genomic DNA fragments by site-directed mutagenesis without double strand breaks. Stability and misfolding of pegRNA in the leader editor (prime editors) can affect the efficiency of leader editing. The 3' extension of the pegRNA may be exposed in the cell and more susceptible to degradation by the nucleic acid exoenzyme than the sgRNA protected by Cas9 protein. We have filed a related patent that exploits tPEs to increase editing efficiency by adding an RNA neck loop structure at the 3 'end of the pegRNA and by allowing the 3' end of the pegRNA to bind to Cas 9. On the basis of tPEs, the pegRNA is divided into two parts, namely the sgRNA and the lead RNA (prime RNA), so that the SnPEs are developed, and the chemical synthesis and modification of the RNA are facilitated. Inducible SniEs have also been developed for achieving temporal and spatial control of lead editing. According to the invention, the 3 'extension part is separated from the pegRNA, and different RNA aptamers are added to the separated 3' extension part or the 3 'extension part is cyclized, so that the 3' extension part is protected from degradation, and the combination stability of Cas9 and the sgRNA is ensured. And i developed inducible lead editing tools.
It is an object of the present invention to provide a gene leader editing system comprising a vector containing a gene encoding sgRNA, a gene encoding an isolated leader RNA comprising a reverse transcription template RTT, a primary binding site PBS, an RNA stem loop structure, and a gene encoding a fusion protein.
The fusion protein is a fusion protein of an RNA binding protein RBP, cas9 incision enzyme or a variant thereof and reverse transcriptase; alternatively, the fusion protein comprises: a first fusion protein comprising an RNA-binding protein RBP and a first inducible binding molecule, and a second fusion protein fragment comprising a Cas9 nickase or a variant thereof, a reverse transcriptase, a second inducible binding molecule.
The RNA stem-loop structure is selected from at least one of the following:
1) MS2, PP7, comBS, csy4BS and box B with sequences shown in SEQ ID NO. 1-5 respectively;
2) An RNA sequence obtained by adding one or more nucleotides to the 5 'end and/or the 3' end of 1);
3) An RNA sequence having an identity of 85% or more to the RNA sequence of 1) or 2).
The RNA stem-loop structure is linked to the 3 'end of the primary binding site PBS, and/or the 5' end of the reverse transcription template RTT;
the separated precursor RNA sequentially comprises a reverse transcription template RTT, a main binding site PBS and an RNA stem loop structure from a 5 'end to a 3' end;
the separated lead RNA sequentially comprises an RNA stem loop structure, a reverse transcription template RTT and a main binding site PBS from the 5 'end to the 3' end;
the isolated guide RNA is linear or circular;
the RBP is a protein which specifically binds to an RNA stem-loop structure; the RBP is one or more;
the carrier is one or more;
the gene encoding the sgRNA, the gene encoding the isolated leader RNA and the gene encoding the fusion protein are one or more;
the gene for encoding the sgRNA, the gene for encoding the isolated leader RNA and the gene for encoding the fusion protein are positioned on the same carrier or different carriers;
the first induced binding molecule and the second induced binding molecule are molecules suitable for binding by the induced molecules;
the first induced binding molecule is located at the N-terminus or the C-terminus of RBP;
the second fusion protein fragment sequentially comprises a second induction binding molecule, cas9 or a variant thereof and reverse transcriptase from the N end to the C end; or, the second fusion protein fragment comprises Cas9 or a variant thereof, reverse transcriptase, and a second induced binding molecule in order from the N-terminus to the C-terminus.
The RBP is selected from any one of tdMCP, tdPCP, COM, csy H29A, N p;
the Cas9 nickase is H840A;
the reverse transcriptase is MMLV;
the first induction molecule and the second induction molecule are respectively and independently selected from two pairs of proteins FKBP and FRB or ABI and PYL 1; that is, when the first inducing molecule is FKBP (SEQ ID NO. 13), the second inducing molecule is FRB (SEQ ID NO. 14); when the first inducing molecule is FRB (SEQ ID NO. 14), the second inducing molecule is FKBP (SEQ ID NO. 13); when the first inducing molecule is ABI (SEQ ID NO. 12), the second inducing molecule is PYL1 (SEQ ID NO. 11); when the first inducing molecule is PYL1 (SEQ ID NO. 11), the second inducing molecule is ABI (SEQ ID NO. 12).
The system also contains a selectable marker protein.
It is a further object of the present invention to provide an isolated leader RNA as described in any of the above systems.
It is another object of the invention to provide a fusion protein comprising the RNA binding protein RBP and a first induction binding molecule, or alternatively, a Cas9 nickase or a variant thereof, a reverse transcriptase and a second induction binding molecule.
The first induced binding molecule and the second induced binding molecule are molecules suitable for binding by the induced molecules;
the first induction molecule and the second induction molecule are respectively and independently selected from two pairs of proteins FKBP and FRB or ABI and PYL 1; that is, when the first inducing molecule is FKBP (SEQ ID NO. 13), the second inducing molecule is FRB (SEQ ID NO. 14); when the first inducing molecule is FRB (SEQ ID NO. 14), the second inducing molecule is FKBP (SEQ ID NO. 13); when the first inducing molecule is ABI (SEQ ID NO. 12), the second inducing molecule is PYL1 (SEQ ID NO. 11); when the first inducing molecule is PYL1 (SEQ ID NO. 11), the second inducing molecule is ABI (SEQ ID NO. 12).
The Cas9 nickase is H840A;
the reverse transcriptase is MMLV.
It is a further object of the present invention to provide a nucleic acid encoding an isolated leader RNA and/or fusion protein as described above.
It is a further object of the present invention to provide a construct comprising a nucleic acid as described above.
It is a further object of the present invention to provide a host cell comprising a construct as described above or a nucleic acid as described above integrated into the genome as described above.
Use of the system, isolated leader RNA, fusion protein, nucleic acid, construct or host cell of any of the above in at least one of:
1) Editing genomic sequences for an organism or a biological cell; preferably for base substitution;
2) An edited product for preparing a genomic sequence of an organism or a biological cell;
3) For improving the efficiency of editing genomic sequences of an organism or a biological cell;
4) For the preparation of products which increase the efficiency of editing of genomic sequences of organisms or biological cells.
For DNA editing or RNA editing; preferably for DNA editing; further preferably, for editing of runx1_ +5 site; even more preferably, for editing of runx1_ +5g·c to t·a.
It is another object of the present invention to provide a method for gene editing comprising introducing a system, isolated guide RNA, fusion protein, nucleic acid, construct or host cell as described in any of the above into a body to be edited to effect editing of a gene.
Drawings
Fig. 1 comparison of SnPE editing efficiency using different aptamers linked to Cas 9.
Figure 2 split-pegRNA maintains PE activity by binding guide RNA to Cas 9-H840A.
FIG. 3 (a) schematic of SnPE with Com, box B or Csy4 aptamer. The snPE-Com, -Box B or-Csy 4 consists of a Cas9H840A-MMLV fused to the N-terminus of the cognate RNP for ligation to a Com binding site (ComBS), box B or Csy4 binding site (Cys 4 BS) at the 5' end of the guide RNA (pRNA). (b-d) edit efficiency of PE, snPE, snPE-5' -Com, snPE-5' -box b and SnPE-5' -Cys4 at runx1_ +5g·c to t·a sites in HEK293FT cells (b) U2OS cells (C) and HeLa cells (d).
FIG. 4 (A) Sanger sequencing of SnPE, snPEa-5' -MS2 mediated RUNX1_5G.C to T.A point mutations using the FKBP/FRB and PYL1-ABI induction systems was tested in HEK293FT cells. (B) Statistics from Sanger sequencing data in (b).
FIG. 5. Schematic of a split pegRNA leader editor. Resolution pegRNA leader editor (Split pegRNA Prime Editors, snPE) contains Cas9-H840A (sky blue), sgRNA and isolated leader RNA (Prime RNA, pRNA) fused with C-terminal reverse transcriptase MMLV (yellow) and N-terminal RNA binding protein (RNA binding protein, RBP) (blue). pRNA consists of one major binding site (PBS, blue-green), one reverse transcription template (RTT, red-violet), and one RNA stem-loop structure such as MS2 or PP7 (orange). SnPE-5 'is MS2 or PP7 at the 5' end and SnPE-3 'is MS2 or PP7 at the 3' end. SnPE-c-MS2 or PP7 comprises a cyclic pRNA (cpRNA) with MS2 or PP 7.
FIG. 6. Schematic of a split pegRNA inducible leader editor. Resolution pegRNA inducible leader editor (Split pegRNA inducible Prime Editors, sniPrs) contains FRB-Cas9-H840A-MMLV (sky blue), FKBP (orange) -MCP (blue), sgRNA and isolated leader RNA (Prime RNA, pRNA) fused to the C-terminal reverse transcriptase MMLV (yellow) and the N-terminal FRB protein (green). pRNA consists of one major binding site (PBS, blue-green), one reverse transcription template (RTT, red-violet), and one RNA stem-loop structure such as MS2 or PP7 (orange). SnPE-5 'is MS2 or PP7 at the 5' end and SnPE-3 'is MS2 or PP7 at the 3' end. SnPE-c-MS2 or PP7 comprises a cyclic pRNA (cpRNA) with MS2 or PP 7.
FIG. 7.PPB-SnPE-ALL-RNA contains three types of pRNA: pSnPE-5'-pRNA, pSnPE-3' -pRNA and pSnPE-circ-pRNA.
Detailed Description
The invention will be further illustrated with reference to specific examples. It is to be understood that these examples are illustrative of the present invention and are not intended to limit the scope of the present invention. The specific conditions are not noted in the examples and are carried out according to conventional conditions or conditions recommended by the manufacturer. The reagents or apparatus used were not manufacturer-specific and were considered conventional products available commercially.
The editing efficiency is improved by separating the 3 'extension part from the pegRNA, adding different RNA aptamers to the separated 3' extension part or cyclizing the 3 'extension part, so that the 3' extension part is protected from degradation and the stability of the combination of Cas9 and the sgRNA is ensured. And on this basis, inducible gene editing tools were developed. To demonstrate the possibility of this approach, the present invention first tested the editing efficiency of runx1_ +5g to T in 293ft, u2os and Hela cells, first added RNA-binding proteins MCP and PCP to the N-terminus of Cas9 to form MCP-Cas9-MMLV and PCP-Cas9-MMLV fusion proteins, then bound MS2 and PP7 aptamers to the 5' and 3' ends of the free 3' extension, forming snPEa (MCP) -5' -MS2, snPEa (MCP) -3' -MS2, snPEa (PCP) -5' -PP7 and snPEa (PCP) -3' -PP7, and cyclized SnPE-MS2 and SnPE-PP7 to form SnPE (MCP) -c-MS2 and snPEa (MCP) -c-PP7 (example 1).
To verify the effect of the stronger RNA binding protein, we fused tdMCP, and tdPCP to the N-terminus of Cas9, forming tdMCP-Cas9-MMLV and tdPCP-Cas9-MMLV fusion proteins, and then bound MS2 and PP7 aptamers to the 5 'end of the free 3' extension, forming snPEa (MCP) -5'-MS2, snPEa (PCP) -5' -PP7, and tested the edit efficiency of runx1_ +5g to T in 293FT cells. And editing results were obtained by Sanger sequencing (example 2).
To verify that this method is not limited to the case of both MS2 and PP7 RNA aptamers, the present invention tested that different RNA aptamers such as com, box b and Csy4 bind to the 5-terminus of the free 3' extension and that the editing efficiency of runx1_ +5g to T was tested in 293FT cells (example 3).
Example 1.
To make PE more flexible, the invention splits the modified pegRNA in tPE into sgRNA and guide RNA (pRNA) and generates a split pegRNA guide editor (SnPE). To stabilize pRNA expression, circular primer RNAs (cpRNA) were generated by the Tornado circRNA expression system. The invention tests the editing efficiency of the Runx1 locus of SnPEa (MCP) -MS2/PP7 or SnPEb (tdMCP) -MS2/PP7 in HEK293 FT. When control pRNA without MS2 or PP7 was used in HEK293FT cells, snPE activity was very low. The combination of pRNA with MS2 or PP7 significantly improved PE efficiency. SnPEa-5'-MS2 or PP7 shows higher activity than SnPEb-3' -MS2 or PP 7.
Example 1.
Fig. 1 comparison of SnPE editing efficiency using different aptamers linked to Cas 9. Schematic of (a) SnPEa and SnPEb. SnPEa-MS2 or PP7 is formed by fusing Cas9H840A-MMLV with the N end of an RBP (SnPEa) or series RBP (SnPEb), wherein the RBP can be combined with MS2 or PP7, and MS2 or PP7 is added to the 5' end of the guide RNA (pRNA). (b) Sanger sequencing of PE, snPE, snPEa-5'-MS2 or PP7 and SnPEb-5' -MS2 or PP7 mediated RUNX1_5G.C to T.A point mutations was tested in HEK293FT cells. (c) Statistics from Sanger sequencing data in (b).
Example 2
The invention tests Runx1 locus in HEK293FT, U2OS and HeLa cells, and tests the influence of splitting pegRNA on PE efficiency. When SnPEa-5'-MS2, snPEa-c-MS2 or SnPEa-5' -PP7 is used, the PE efficiency is comparable to that of the standard PE. In HEK293FT cells, the activity of SnPE-5'-MS2 is 82.3%, the efficiency of SnPE-c-MS2 is 72.1%, the efficiency of SnPE-5' -PP7 is 59.4%, and the efficiency of SnPEa-c-PP7 is 46.0%. When SnPEa-3'-MS2 (31.7%) or SnPEa-3' -PP7 (18.3%) is used, the efficiency becomes much lower. Consistent with the results of HEK293FT cells (2 a), the inefficiency of SnPE was observed when the control pRNA, pRNA-3'-MS2 or pRNA-3' -PP7 was used in U2OS (2 b) or HeLa (2 c) cells. The highest PE efficiency was found when SnPEa-5'-PP7 (79.5% of the canonical PE) was used in U2OS and SnPEa-5' -MS2 (59.8%) was used in HeLa cells. In all three cell types (2 d-f), the editing/insertion/deletion ratio of SnPEs was slightly lower than that of canonical PE, consistent with the level change in PE activity.
Figure 2 split-pegRNA maintains PE activity by binding guide RNA to Cas 9-H840A. Editing efficiency of SnPE-5'-MS2 or PP7, snPE-3' -MS2 or PP7, snPE-C-MS2 or PP7 mediated runx1_ +5g·c to t·a sites in HEK293FT cells (a), U2OS cells (b) and HeLa cells (C). The ratio of editing efficiency to indels of the SnPE-5'-MS2 or PP7, snPE-3' -MS2 or PP7, snPE-C-MS2 or PP7 mediated runx1_ +5g·c to t·a sites in HEK293FT cells (d), U2OS cells (e) and HeLa cells (f).
Example 3
The present invention further tested whether ligation of pRNA to other aptamers such as pRNA-5' -ComBS, pRNA-5' -Box B or pRNA-5' -Cys 4BS could also retain SnPE activity. Among these aptamers, the activity of SnPE-5' -Com was 68.6% of the original PE in HEK293FT cells, 57.3% of the original PE in U2OS cells and 65.5% of the original PE in HeLa cells. These results indicate that the SnPE maintains the activity of the original PE and increases the flexibility of the boot editing system.
FIG. 3 (a) schematic of SnPE with Com, box B or Csy4 aptamer. The snPE-Com, -Box B or-Csy 4 consists of a Cas9H840A-MMLV fused to the N-terminus of the cognate RNP for ligation to a Com binding site (ComBS), box B or Csy4 binding site (Cys 4 BS) at the 5' end of the guide RNA (pRNA). (b-d) edit efficiency of PE, snPE, snPE-5' -Com, snPE-5' -box b and SnPE-5' -Cys4 at runx1_ +5g·c to t·a sites in HEK293FT cells (b) U2OS cells (C) and HeLa cells (d).
Example 4
In order to verify that the SnPE has practical application value, the invention develops an inducible PE editing system. The two induction systems are FKBP/FRB and ABI/PYL1 induction systems respectively, wherein the FRB/FKBP can be combined together through rapamycin induction, and the ABI/PYL1 can be combined together through ABA induction. Preliminary results from Sanger sequencing revealed that RUNX1_ +5G.C to T.A sites could be efficiently edited after induction by SnPE-MS2 relative to control SnPE in 293FT cells.
FIG. 4 (A) Sanger sequencing of SnPE, snPEa-5' -MS2 mediated RUNX1_5G.C to T.A point mutations using the FKBP/FRB and PYL1-ABI induction systems was tested in HEK293FT cells. (B) Statistics from Sanger sequencing data in (b).
Specifically, the experimental method comprises the following steps:
1.1 Experimental materials
1.1.1 reagents and plasmids
Primers were synthesized from Suzhou gold only biological Co., ltd; restriction enzymes, DNA ligases, high fidelity DNA polymerasesPurchased from NEB company; plasmid recombination kit Clone->He Jiao recovery kit>Purchased from Vazyme company; pCMV-BE3 from the adedge website; transfection reagent->2000，/>Purchased from Thermo Fisher company; quickExract TM Genomic DNA extraction reagents were purchased from Illumina.
1.1.2 cell lines
Human fetal kidney cells HEK293FT (Thermo Fisher Scientific), human osteosarcoma cells U2OS and human cervical cancer cells Hela cells were cultivated in adherent manner in DMEM medium (Gibco) supplemented with 10% fetal bovine serum (Gbico) and 1% diab.
1.2 Experimental methods
1.2.1 construction of expression plasmids
The modified pegRNA or split-pegRNA expression plasmid pPB-SnPE-ALL-RNA for SnPE was generated in two steps (FIG. 7). First, pSnPE-5'-pRNA, pSnPE-3' -pRNA, pSnPE-circ-pRNA, pSnPE-sgRNA and pPE3-sgRNA were constructed, respectively. For pSnPE-5'-pRNA, pSnPE-3' -pRNA and pSnPE-circ-pRNA (supplementary Table 1), the synthetic oligonucleotides were ligated with 5'ACCG and 3' AAAA in the upstream and downstream primers and annealed, and cloned into the pLH-AAAA backbone plasmid (supplementary sequence S1). For pSnPE-sgRNA and pPE3-sgRNA, the synthetic oligonucleotides were ligated with 5'ACCG and 3' AAAC on the upstream and downstream primers and annealed, and then cloned into the pLH-sgRNA3 backbone vector (complement S1). Finally, the relevant sequence was cloned into a vector pDONR5.1 (complement S1) using Golden gate and the pPB-SnPE-ALL-RNA plasmid was generated.
The RBP-SpCas9-MMLV expression plasmid was generated on top of pCMV-PE2 (#addgene 132775), where PE2 refers to SpCas9H840A-MMLV (supplementary fig. 1 b). First, T2A-GFP was inserted into the C-terminus of pCMV-PE2 to construct a pCMV-PE2-T2A-GFP plasmid. Next, RNA binding proteins including stem loop aptamers for tdMCP, com, csy H29A and tdPCP (complement S2) were synthesized and cloned into pCMV-PE2-T2A-GFP using a ClonExpress II one-step cloning kit (Vazyme, C112-01) to give pCMV-tdMCP-PE2-T2A-GFP, pCMV-Com-PE2-T2A-GFP, pCMV-Csy4H29A-PE2-T2A-GFP and pCMV-tdPCP-PE2-T2A-GFP plasmids, respectively.
The inducible edited expression plasmid is based on pCMV-PE2-T2A-GFP plasmid, and the synthesized FRB and ABI proteins are cloned to obtain pCMV-FRB-PE2-T2A-GFP and pCMV-ABI-PE2-T2A-GFP (supplementary sequence S1). pCMV-FKBP-MCP and pCMV-PYL1-MCP (complementary sequence S1) are obtained by cloning FKBP and PYL1 proteins on the basis of pCMV-MCP plasmid.
The PCR system used to amplify the various fragments in the plasmid construction experiments in step 1.2.1 was as follows:
TABLE 1.2.1.1 PCR amplification System
TABLE 1.2.1.2 PCR procedure
Table 1.2.1.3 annealing procedure
TABLE 1.2.1.4 homologous recombination reactions
Table 1.2.1.5 sgRNA Golden Gate Assembly reaction
1.2.2 cell culture and transfection and genome extraction
HEK293FT (Thermo Fisher Scientific), heLa (ATCC, CCL-2) and U2OS (ATCC, HTB-96) cells were cultured in DMEM medium containing high glucose 10% fbs (fetal bovine serum, thermo Fisher Scientific). All cells were cultured in a humidified incubator at 37℃with 5% CO 2. Prior to transfection, cells were seeded in 12-well plates at a cell density of approximately 60% and transfected using Lipofectamine 2000 (Thermo Fisher Scientific). To measure gene editing efficiency, 50. Mu.L opti-DMEM, 1.5. Mu.g Prime editor 2 (PE 2, dCAS 9-MMLV) or RBP-PE2, and 500ng PE-all-RNA, sPE-all-RNA or tPE-all-RNA expression plasmids were added to a 1.5mL centrifuge tube. Vortex to mix thoroughly, add 50. Mu.L opti-DMEM and 4. Mu.L Lipofectamine 2000 transfection reagent into another 1.5. 1.5mL centrifuge tube, and leave it to stand for 5min. Mixing the 2-tube solutions, standing for 15min, and co-transfecting into HEK293FT, U2OS or HeLa cells. 72 hours after transfection, prime editor (GFP+) and PE-all-RNA, sPE-all-RNA, tPE-all-RNA double positive cells were collected using flow cytometry (BD FACS Aria).
1.2.3 extraction of genomic DNA and PCR amplification
The genome of the cells was extracted using QuickExtract DNA Extraction Solution (Lucigen) according to the reagent protocol, and the extracted genomic DNA was subjected to PCR amplification using the following primers (supplementary table 2).
1.2.4 deep sequencing
Genomic sites of interest were amplified from genomic DNA using locus specific primers comprising Truseq adaptors. Equivalent PCR products were pooled and the kit was recovered using gelThe gel was purified. The purified library was deep sequenced using a double-ended 150bp Illumina MiniSeq run.
FIG. 7.PPB-SnPE-ALL-RNA contains three types of pRNA: pSnPE-5'-pRNA, pSnPE-3' -pRNA and pSnPE-circ-pRNA. pSnPE-5'-pRNA consists of the 5' -terminal stem loop (dark green), RTT (gold) and PBS (magenta). pSnPE-3'-pRNA consists of a 3' -end comprising a stem-loop (dark green), RTT (gold) and PBS (magenta). pSnPE-circ-pRNA contains circular sequences at both ends (purple), stem-loop (dark green), RTT (gold) and PBS (magenta). pSnPE-sgRNA contains sgRNA (blue), pPE3-sgRNA contains sgRNAnick (orange), and pDONR5.1 consists of the CcdB gene (green), puromycin (yellow), P2A (purple), and TagBFP2 (cyan).
MS2(SEQ ID NO.1)
Acatgaggatcacccatgt
PP7(SEQ ID NO.2)
Ggagcagacgatatggcgtcgctcc
Com (Com protein binding site) (SEQ ID NO. 3)
CTGAATGCCTGCGAGCATC
Csy4 (Csy 4 protein binding site) (SEQ ID NO. 4)
Actgccgtataggcagctaagaaa
box B (box B RNA binding site) (SEQ ID NO. 5)
ggccctgaagaagggcc
MCP (MS 2 coat protein) (SEQ ID NO. 6)
MASNFTQFVLVDNGGTGDVTVAPSNFANGIAEWISSNSRSQAYKVTCSVRQSSAQNRKYTIKVEVPKGAWRSYLNM ELTIPIFATNSDCELIVKAMQGLLKDGNPIPSAIAANSGIY
PCP (PP 7 coat protein) (SEQ ID NO. 7)
MGSKTIVLSVGEATRTLTEIQSTADRQIFEEKVGPLVGRLRLTASLRQNGAKTAYRVNLKLDQADVVDSGLPKVRYTQV WSHDVTIVANSTEASRKSLYDLTKSLVATSQVEDLVVNLVPLGR
COM (Com RNA binding protein) (SEQ ID NO. 8)
GSMKSIRCKNCNKLLFKADSFDHIEIRCPRCKRHIIMLNACEHPTEKHCGKREKITHSDETVRYGSTSGHKLNGGGGG MDAKSLTAWS
Csy4H29A (Csy 4 binding protein H29A mutant) (SEQ ID NO. 9)
MDHYLDIRLRPDPEFPPAQLMSVLFGKLAQALVAQGGDRIGVSFPDLDESRSRLGERLRIHASADDLRALLARPWLEG LRDHLQFGEPAVVPHPTPYRQVSRVQAKSNPERLRRRLMRRHDLSEEEARKRIPDTVARALDLPFVTLRSQSTGQHFR LFIRHGPLQVTAEEGGFTCYGLSKGGFVPWF
N22p (lambda N22 peptide fragment binding protein) (SEQ ID NO. 10)
GNARTRRRERRAEKQAQWKAAN
PYL1-MCP (Pyricularin binding abscisic acid receptor-MS 2 coat protein fusion protein) (SEQ ID NO. 11)
GGGAPTQDEFTQLSQSIAEFHTYQLGNGRCSSLLAQRIHAPPETVWSVVRRFDRPQIYKHFI KSCNVSEDFEMRVGCTRDVNVISGLPANTSRERLDLLDDDRRVTGFSITGGEHRLRNYKSVT TVHRFEKEEEEERIWTVVLESYVVDVPEGNSEEDTRLFADTVIRLNLQKLASITEAMNKRTAD GSEFESPKKKRKVMASNFTQFVLVDNGGTGDVTVAPSNFANGIAEWISSNSRSQAYKVTCSV RQSSAQNRKYTIKVEVPKGAWRSYLNMELTIPIFATNSDCELIVKAMQGLLKDGNPIPSAIAAN SGIY
ABI (type 2C protein phosphatase) (SEQ ID NO. 12)
TRVPLYGFTSICGRRPEMEAAVSTIPRFLQSSSGSMLDGRFDPQSAAHFFGVYDGHGGSQV ANYCRERMHLALAEEIAKEKPMLCDGDTWLEKWKKALFNSFLRVDSEIESVAPETVGSTSVV AVVFPSHIFVANCGDSRAVLCRGKTALPLSVDHKPDREDEAARIEAAGGKVIQWNGARVFGV LAMSRSIGDRYLKPSIIPDPEVTAVKRVKEDDCLILASDGVWDVMTDEEACEMARKRILLWHK KNAVAGDASLLADERRKEGKDPAAMSAAEYLSKLAIQRGSKDNISVVVVDLK
FKBP-MCP (RAP-mediated FK506 binding protein 12-MS2 coat protein fusion protein) (SEQ ID NO. 13)
MGVQVETISPGDGRTFPKRGQTCVVHYTGMLEDGKKFDSSRDRNKPFKFMLGKQEVIRGW EEGVAQMSVGQRAKLTISPDYAYGATGHPGIIPPHATLVFDVELLKLEKRTADGSEFESPKKKR KVMASNFTQFVLVDNGGTGDVTVAPSNFANGIAEWISSNSRSQAYKVTCSVRQSSAQNRKY TIKVEVPKGAWRSYLNMELTIPIFATNSDCELIVKAMQGLLKDGNPIPSAIAANSGIY
FRB (FKBP 12-rapamycin complex binding site) (SEQ ID NO. 14)
ILWHEMWHEGLEEASRLYFGERNVKGMFEVLEPLHAMMERGPQTLKETSFNQAYGRDLME AQEWCRKYMKSGNVKDLTQAWDLYYHVFRRISK
Supplement table 1
pPE-pegRNA
JAK2-F:
ataattgaagacATaccgACCTGTGACTCATGAAACACgtttgagagctagaaatagcaagttcaaataaggc (SEQ ID NO.15)
JAK2-R:ataattgaagacGCaaaaCTGTGACTCATGAAATACAGGAAGAATGTgcaccgactcggtgcc (SEQ ID NO.16)
HDAC1-F:
ataattgaagacATaccgGCACCATGCAAAGAAGTCCGgtttgagagctagaaatagcaagttcaaataaggc (SEQ ID NO.17)
HDAC1-R:ataattgaagacGCaaaaTGCAAAGAAGTGCGAGGCATCTGGCTgcaccgactcggtgcc (SEQ ID NO.18)
EED-F:
ataattgaagacATaccgCCGGTTGTTGCAATCTTACGgtttgagagctagaaatagcaagttcaaataaggc (SEQ ID NO.19)
EED-R:ataattgaagacGCaaaaGTTGTTGCAATCTTTCGTGGATGCTGATgcaccgactcggtgcc (SEQ ID NO.20)
BCL11A-F:
ataattgaagacATaccgtcacagATAAACTTCTGCACgtttgagagctagaaatagcaagttcaaataaggc(SEQ ID NO.21)
BCL11A-R:
ataattgaagacGCaaaaCACAGATAAACTTCTGAACTGGAGGGGCCgcaccgactcggtgcc(SEQ ID NO.22)
SRD5A3-F:
ataattgaagacATaccgCCTTACTCAATCTCTGTTCCgtttgagagctagaaatagcaagttcaaataaggc (SEQ ID NO.23)
SRD5A3-R:
ataattgaagacGCaaaaTTACTCAATCTCTGTTACTGGGAGCACCTTTTCgcaccgactcggtgcc (SEQ ID NO.24)
SRD5A1-F:
ataattgaagacATaccgTCCATTCAGATCATATCCTAgtttgagagctagaaatagcaagttcaaataaggc(SEQ ID NO.25)
SRD5A1-R:
ataattgaagacGCaaaaCATTCAGATCATATCATAAGGAATCTCAGAAAgcaccgactcggtgcc(SEQ ID NO.26)
DYRK1A-F:ataattgaagacATaccgagcacatcaaggacattctagtttgagagctagaaatagcaagttcaaataaggc (SEQ ID NO.27)
DYRK1A-R:ataattgaagacGCaaaacaaggacattgtaaggatgatgcaccgactcggtgcc(SEQ ID NO.28)
DMD-F:
ataattgaagacATaccgCTACCTCTGTGATACTCTTCgtttgagagctagaaatagcaagttcaaataaggc (SEQ ID NO.29)
DMD-R:ataattgaagacGCaaaaACCTCTGTGATACTCCTCAGGTGCACCTgcaccgactcggtgcc (SEQ ID NO.30)
RUNX1-F:ataattgaagacATaccggcattttcaggaggaagcgagtttgagagctagaaatagcaagttcaaataaggc (SEQ ID NO.31)
RUNX1-R:ataattgaagacGCaaaaattttcaggaggaagcgattgcttcagacagcaccgactcggtgcc(SEQ ID NO.32)
GFAP-F:ataattgaagacATaccgagcctgtgtccatataaagggttttagagctagaaatagcaagttaaaataaggctagtc (SEQ ID NO.33)
GFAP-R:ataattgaagacGCaaaaTGTGTCCATATAATGGAGGAGTTGGAAgcaccgactcggtgcc (SEQ ID NO.34)
psPE-pegRNA
JAK2-MS2-F:
ataattgaagacATaccgACCTGTGACTCATGAAACACgtttgagagctagaaatagcaagttcaaataaggc (SEQ ID NO.35)
JAK2-MS2-R:
ataattgaagacGCaaaaacatgggtgatcctcatgtCTGTGACTCATGAAATACAGGAAGAATGTgcaccga ctcggtgcc(SEQ ID NO.36)
HDAC1-MS2-F:
ataattgaagacATaccgGCACCATGCAAAGAAGTCCGgtttgagagctagaaatagcaagttcaaataaggc (SEQ ID NO.37)
HDAC1-MS2-R:
ataattgaagacGCaaaaacatgggtgatcctcatgtTGCAAAGAAGTGCGAGGCATCTGGCTgcaccgactc ggtgcc(SEQ ID NO.38)
EED-MS2-F:
ataattgaagacATaccgCCGGTTGTTGCAATCTTACGgtttgagagctagaaatagcaagttcaaataaggc (SEQ ID NO.39)
EED-MS2-R:
ataattgaagacGCaaaaacatgggtgatcctcatgtGTTGTTGCAATCTTTCGTGGATGCTGATgcaccgact cggtgcc(SEQ ID NO.40)
BCL11A-MS2-F:
ataattgaagacATaccgtcacagATAAACTTCTGCACgtttgagagctagaaatagcaagttcaaataaggc(SEQ ID NO.41)
BCL11A-MS2-R:
ataattgaagacGCaaaaacatgggtgatcctcatgtCACAGATAAACTTCTGAACTGGAGGGGCCgcaccg actcggtgcc(SEQ ID NO.42)
SRD5A3-MS2-F:
ataattgaagacATaccgCCTTACTCAATCTCTGTTCCgtttgagagctagaaatagcaagttcaaataaggc (SEQ ID NO.43)
SRD5A3-MS2-R:
ataattgaagacGCaaaaacatgggtgatcctcatgtTTACTCAATCTCTGTTACTGGGAGCACCTTTTCgc accgactcggtgcc(SEQ ID NO.44)
SRD5A1-MS2-F:
ataattgaagacATaccgTCCATTCAGATCATATCCTAgtttgagagctagaaatagcaagttcaaataaggc(SEQ ID NO.45)
SRD5A1-MS2-R:
ataattgaagacGCaaaaacatgggtgatcctcatgtCATTCAGATCATATCATAAGGAATCTCAGAAAgcac cgactcggtgcc(SEQ ID NO.46)
DYRK1A-MS2-F:
ataattgaagacATaccgagcacatcaaggacattctagtttgagagctagaaatagcaagttcaaataaggc(SEQ ID NO.47)
DYRK1A-MS2-R:
ataattgaagacGCaaaaacatgggtgatcctcatgtcaaggacattgtaaggatgatgcaccgactcggtgcc(SEQ ID NO.48)
DMD-MS2-F:
ataattgaagacATaccgCTACCTCTGTGATACTCTTCgtttgagagctagaaatagcaagttcaaataaggc (SEQ ID NO.49)
DMD-MS2-R:
ataattgaagacGCaaaaacatgggtgatcctcatgtACCTCTGTGATACTCCTCAGGTGCACCTgcaccgac tcggtgcc(SEQ ID NO.50)
RUNX1-MS2-F：
ataattgaagacATaccggcattttcaggaggaagcgagtttgagagctagaaatagcaagttcaaataaggc(SEQ ID NO.51)
RUNX1-MS2-R:ataattgaagacGCaaaaacatgggtgatcctcatgtattttcaggaggaagcgattgcttcagacagcaccgactcggtgcc (SEQ ID NO.52)
GFAP-MS2-F:
ataattgaagacATaccgagcctgtgtccatataaagggttttagagctagaaatagcaagttaaaataaggctagtc(SEQ ID NO.53)
GFAP-MS2-R:
ataattgaagacGCaaaaacatgggtgatcctcatgtTGTGTCCATATAATGGAGGAGTTGGAAgcaccgactc ggtgcc(SEQ ID NO.54)
RUNX1-com-F:
ataattgaagacATaccggcattttcaggaggaagcgagtttgagagctagaaatagcaagttcaaataaggc(SEQ ID NO.55)
RUNX1-com-R:
ataattgaagacGCaaaaGATGCTCGCAGGCATTCAGattttcaggaggaagcgattgcttcagacagcaccgact cggtgcc(SEQ ID NO.56)
RUNX1-pp7-F:
ataattgaagacATaccggcattttcaggaggaagcgagtttgagagctagaaatagcaagttcaaataaggc(SEQ ID NO.57)
RUNX1-pp7-R:
ataattgaagacGCaaaaggagcgacgccatatcgtctgctccattttcaggaggaagcgattgcttcagacagcaccgactcg gtgcc(SEQ ID NO.58)
RUNX1-csy4-F:
ataattgaagacATaccggcattttcaggaggaagcgagtttgagagctagaaatagcaagttcaaataaggc(SEQ ID NO.59)
RUNX1-csy4-R：
ataattgaagacGCaaaaCTGCCTATACGGCAGTGAACattttcaggaggaagcgattgcttcagacagcaccga ctcggtgcc(SEQ ID NO.60)
pPE3-sgRNA
JAK2-F:accgTGGGGTTTGATCGTTTTCTT(SEQ ID NO.61)JAK2-R: aaacAAGAAAACGATCAAACCCCA(SEQ ID NO.62)
HDAC1-F:accgATACTTTAGCAGTTCCAGG(SEQ ID NO.63)HDAC1-R: aaacTCCTGGAACTGCTAAAGTAT(SEQ ID NO.64)
EED-F:accgTGATTAATTTATAAAAGTTT(SEQ ID NO.65)EED-R: aaacAAACTTTTATAAATTAATCA(SEQ ID NO.66)
BCL11A-F:accgCTGCACTCATCCCAGGCGTG(SEQ ID NO.67)BCL11A-R: aaacCACGCCTGGGATGAGTGCAG(SEQ ID NO.68)
SRD5A3-F:accgCCAGTAACAGAGATTGAGTA(SEQ ID NO.69)SRD5A3-R: aaacTACTCAATCTCTGTTACTGG(SEQ ID NO.70)
SRD5A1-F:accgTCCTTATGATATGATCTGAA(SEQ ID NO.71)SRD5A1-R: aaacTTCAGATCATATCATAAGGA(SEQ ID NO.72)
DYRK1A-F:accgAAGAGTGAGGAGAAGGCAGG(SEQ ID NO.73)DYRK1A- R:aaacCCTGCCTTCTCCTCACTCTT(SEQ ID NO.74)
DMD-F:accgGTCAATGCTCTCCTTTTCAC(SEQ ID NO.75)DMD- R:aaacGTGAAAAGGAGAGCATTGAC(SEQ ID NO.76)
RUNX1-F:accgCATGTACTCACCTCTCATGA(SEQ ID NO.77)RUNX1-R: aaacTCATGAGAGGTGAGTACATG(SEQ ID NO.78)
Supplement table 2
Gene
JAK2-F:ctacacgacgctcttccgatctgTGGCGGCATGATTTTGT(SEQ ID NO.79)JAK2-R: agacgtgtgctcttccgatctccaagcattttagataag(SEQ ID NO.80)
HDAC1-F:ctacacgacgctcttccgatcttcatgcccagCAAGTGCTGTGAAAC(SEQ ID NO.81)HDAC1- R:agacgtgtgctcttccgatctgacactcaccgagcacatcctagcc(SEQ ID NO.82)
EED-F:ctacacgacgctcttccgatctagttggagagagtatgttttctatacttgagatga(SEQ ID NO.83)EED-R: agacgtgtgctcttccgatctaactagatacaggattctcttgggtgatagtg(SEQ ID NO.84)
BCL11A-F:ctacacgacgctcttccgatcttattttaatggaattgaaatgtgatatcctgtggtttatgatg(SEQ ID NO.85)
BCL11A-R:agacgtgtgctcttccgatctccttcagtacttaaaaagtaagggcaatttccagaaa(SEQ ID NO.86)
SRD5A3-F:ctacacgacgctcttccgatcttgcctcgcttgttttccttttgcagAT(SEQ ID NO.87)SRD5A3-R: agacgtgtgctcttccgatctgcccttctgaggaggtgccg(SEQ ID NO.88)
SRD5A1-F:ctacacgacgctcttccgatctgaaattttacggtttattagccataatcatcttgcaa(SEQ ID NO.89)
SRD5A1-R:agacgtgtgctcttccgatctgatgacttacactgaaaacttgtagctaataactactacg(SEQ ID NO.90)
DYRK1A-F:ctacacgacgctcttccgatctcttgtcacacacaatgaaactttgctgttcact(SEQ ID NO.91)
DYRK1A-R:agacgtgtgctcttccgatctagtagctaacatttttcagtacttaactatatgccagctat(SEQ ID NO.92)
DMD-F:ctacacgacgctcttccgatctAAGCATTAAATCTTAAGACTACAAGACATTACTTGAAGG (SEQ ID NO.93)DMD-R:agacgtgtgctcttccgatctGACAGAGAAGGGTGTAAAAGCTTCTAGC (SEQ ID NO.94)
RUNX1-F:ctacacgacgctcttccgatcttggttttcgctccgaagGTAAAAGAA(SEQ ID NO.95)RUNX1- R:agacgtgtgctcttccgatctatatgcctcagtttgaattcctctcacaaacaag(SEQ ID NO.96)
GFAP-F：ctacacgacgctcttccgatcttactggggaaagcagtgcaggagca(SEQ ID NO.97)GFAP-R: agacgtgtgctcttccgatctaccaccgcttcacagctgtgc(SEQ ID NO.98)
Supplementary Table 3
Gene
JAK2:gTGGCGGCATGATTTTGTGCACGGATGGATAAAAGTACCTGTGACTCATGAAACACA GGAAGAATGTCTTGGGATGGCAGTGTTAGATATGATGAGAATAGCCAAAGAAAACGATCAA ACCCCACTGGCCATCTATAACTCTATCAGgtaattttcttttgcaaatccttacacataagtgtgagtagagattttat ataattcgtatatattttctgtgtttacccatgccttttgattttgtaatactagttaagtactccttatctaaaatgcttgg(SEQ ID NO.99)
HDAC1:tcatgcccagCAAGTGCTGTGAAACTTAATAAGCAGCAGACGGACATCGCTGTGAATT GGGCTGGGGGCCTGCACCATGCAAAGAAGTCCGAGGCATCTGGCTTCTGTTACGTCAAT GATATCGTCTTGGCCATCCTGGAACTGCTAAAgtatgcctgcctggccttgtctcttggaagagcaccttaggcc aggttcccatttccctcttcccctgggcttgcctccctagtttgcttttcctaccgatgtgctggctaggatgtgctcggtgagtgtc(SEQ ID NO.100)
EED:agttggagagagtatgttttctatacttgagatgaaatttactgtatttttattttcattagGTTACCTTGTATGAATGTC ATTCACAAGGAGAAATCCGGTTGTTGCAATCTTACGTGGATGCTGATgtatcctttcctgggtttttaat atctttagtcaaaggaatttattttcaataagtgcaccaaaacttttataaattaatcatttccctaaagttattgttctttcttaaccgatttctt cactatcacccaagagaatcctgtatctagtt(SEQ ID NO.101)
BCL11A:tattttaatggaattgaaatgtgatatcctgtggtttatgatgcacgttgtttgtagctgtagtgcttgattttgggtttctttcaca gATAAACTTCTGCACTGGAGGGGCCTCTCCTCCCCTCGTTCTGCACATGGAGCTCTAATC CCCACGCCTGGGATGAGTGCAGAATATGCCCCGCAGGGTATTTgtaagttgagccttatttcttctacaa atgtccatgtgtatagagatgagaatttctggaaattgcccttactttttaagtactgaagg(SEQ ID NO.102)
SRD5A3:tgcctcgcttgttttccttttgcagATATTTTTCCCACTTTTATATCATCTCAGTGCTGTGGAATG GCTTCCTGCTTTGGTGCCTTACTCAATCTCTGTTCCTGGGAGCACCTTTTCCAAGCTGGC TTCATGGTTTGCTCAGAATTCTCGGGGCGGCACAGTTCCAGGgtaaggactccctgggcttatgaca acgctgcatcccgtttctgttgttcctgtctgcaagggagcagtttttggcattttgtctcctctctcggcacctcctcagaagggc(SEQ ID NO.103)
SRD5A1:
gaaattttacggtttattagccataatcatcttgcaatttttttcctttagGTTTTGGCTTGTGGTTAACGGGCATGTTG ATAAACATCCATTCAGATCATATCCTAAGGAATCTCAGAAAACCAGGAGATACTGGATACAA AATACCAAGGGgtacgtacagaaagtgaagaatttctgtgaaagttgcttgccatggttcctggctattttagtgttgccagctct aagaagtagtagcgtagtagttattagctacaagttttcagtgtaagtcatc(SEQ ID NO.104)
DYRK1A:
cttgtcacacacaatgaaactttgctgttcactgtcagttataacttacatgaggtgacccatttccattcaagggttttagaagcacatc aaggacattctaaggatgattgacttacacaatgatctctgaacatgcctcctgccttctcctcactcttgagtatttgcttaggggagca gaaaaaatactggtagcattactgtaacattttaattctgctttatttaaaaaagacatagctggcatatagttaagtactgaaaaatgtt agctact(SEQ ID NO.105)
DMD:
AAGCATTAAATCTTAAGACTACAAGACATTACTTGAAGGTCAATGCTCTCCTTTTCACAGGC TACTCAAAAAGAGATTGAGAAACAGAAGGTGCACCTGAAGAGTATCACAGAGGTAGGAGA GGCCTTGAAAACAGTTTTGGGCAAGAAGGAGACGTTGGTGGAAGATAAACTCAGTCTTCT GAATAGTAACTGGATAGCTGTCACCTCCCGAGCAGAAGAGTGGTTAAATCTTTTGTTGGTA AGAGAAAAGGCTAGAAGCTTTTACACCCTTCTCTGTC(SEQ ID NO.106)
RUNX1:
tggttttcgctccgaagGTAAAAGAAATCATTGAGTCCCCCGCCTTCAGAAGAGGGTGCATTTTCA GGAGGAAGCGATGGCTTCAGACAGCATATTTGAGTCATTTCCTTCGTACCCACAGTGCTT CATGAGAGgtgagtacatgctggtcttgtaatatctacttttgctcagctttgcctgtaatgaaatggcagcttgtttcacctcggtgc agagatgcctcggtgcctgccagttccctgtcttgtttgtgagaggaattcaaactgaggcatat(SEQ ID NO.107)
GFAP:
tactggggaaagcagtgcaggagcagcggggcccctgtgtttcattcatggctgggctttgtgactgtgggcagcgagctcacctat tctgagcctgtgtccatataaaggaggagttggaagcggagaaggttgatgtccatgagggagattggattctggggtgaagaaa gtgagggaaagagcaggcaggtctgggcgcaaagcacaggtgactgcctgccaccagcttgtgacccccatcaagttactttga cttgcacagctgtgaagcggtggt(SEQ ID NO.108)
Complement sequence 1
pDONOR 5.1
acggatcgggagatctaccggtacgcgttgacgtgtcttcggatccggcttactaaaagccagataacagtatgcgtatttgcgcgc tgatttttgcggtataagaatatatactgatatgtatacccgaagtatgtcaaaaagaggtatgctatgaagcagcgtattacagtgac agttgacagcgacagctatcagttgctcaaggcatatatgatgtcaatatctccggtctggtaagcacaaccatgcagaatgaagc ccgtcgtctgcgtgccgaacgctggaaagcggaaaatcaggaagggatggctgaggtcgcccggtttattgaaatgaacggctct tttgctgacgagaacaggggctggtgaaatgcagtttaaggtttacacctataaaagagagagccgttatcgtctgtttgtggatgtac agagtgatattattgacacgcccgggcgacggatggtgatccccctggccagtgcacgtctgctgtcagataaagtctcccgtgaa ctttacccggtggtgcatatcggggatgaaagctggcgcatgatgaccaccgatatggccagtgtgccggtctccgttatcgggga agaagtggctgatctcagccaccgcgaaaatgacatcaaaaacgccattaacctgatgttctggggaatataaatgtcaggctcc cttatacacagccagtctgcaggtcgacgaagacccactcgcggccgcttggggttgcgccttttccaaggcagccctgggtttgcg cagggacgcggctgctctgggcgtggttccgggaaacgcagcggcgccgaccctgggtctcgcacattcttcacgtccgttcgca gcgtcacccggatcttcgccgctacccttgtgggccccccggcgacgcttcctgctccgcccctaagtcgggaaggttccttgcggtt cgcggcgtgccggacgtgacaaacggaagccgcacgtctcactagtaccctcgcagacggacagcgccagggagcaatggc agcgcgccgaccgcgatgggctgtggccaatagcggctgctcagcagggcgcgccgagagcagcggccgggaaggggcgg tgcgggaggcggggtgtggggcggtagtgtgggccctgttcctgcccgcgcggtgttccgcattctgcaagcctccggagcgcac gtcggcagtcggctccctcgttgaccgaatcaccgacctctctccccagggggatccgccaccatgaccgagtacaagcccacg gtgcgcctcgccacccgcgacgacgtccccagggccgtacgcaccctcgccgccgcgttcgccgactaccccgccacgcgcca caccgtcgatccggaccgccacatcgagcgggtcaccgagctgcaagaactcttcctcacgcgcgtcgggctcgacatcggcaa ggtgtgggtcgcggacgacggcgccgcggtggcggtctggaccacgccggagagcgtcgaagcgggggcggtgttcgccgag atcggcccgcgcatggccgagttgagcggttcccggctggccgcgcagcaacagatggaaggcctcctggcgccgcaccggc ccaaggagcccgcgtggttcctggccaccgtcggcgtctcgcccgaccaccagggcaagggtctgggcagcgccgtcgtgctcc ccggagtggaggcggccgagcgcgccggggtgcccgccttcctggagacctccgcgccccgcaacctccccttctacgagcgg ctcggcttcaccgtcaccgccgacgtcgaggtgcccgaaggaccgcgcacctggtgcatgacccgcaagcccggtgccgctag cggtgctactaacttcagcctgctgaagcaggctggagacgtggaggagaaccctggacctggtagtggaacgcgtatggtgtct aagggcgaagagctgattaaggagaacatgcacatgaagctgtacatggagggcaccgtggacaaccatcacttcaagtgcac atccgagggcgaaggcaagccctacgagggcacccagaccatgagaatcaaggtggtcgagggcggccctctccccttcgcct tcgacatcctggctactagcttcctctacggcagcaagaccttcatcaaccacacccagggcatccccgacttcttcaagcagtcctt ccctgagggcttcacatgggagagagtcaccacatacgaagatgggggcgtgctgaccgctacccaggacaccagcctccag gacggctgcctcatctacaacgtcaagatcagaggggtgaacttcacatccaacggccctgtgatgcagaagaaaacactcggc tgggaggccttcaccgagacgctgtaccccgctgacggcggcctggaaggcagaaacgacatggccctgaagctcgtgggcg ggagccatctgatcgcaaacgccaagaccacatatagatccaagaaacccgctaagaacctcaagatgcctggcatctactatg tggactacagactggaaagaatcaaggaggccaacaacgaaacctacgtcgagcagcacgaggtggcagtggccagatact gcgacctccctagcaaactggggcacaagcttaatccaaagaaaaagcggaaagtgtgagtcgacctcgagggggggcccg gtacctttaagaccaatgacttacaaggcagctgtagatcttagccacatgtcatcttattattcagtatttataacttgcaaagaaatga atatcagagagtgagaggaacttgtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataaagcat ttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatcatgtctggaattcacatgtgagcaaaaggccagcaaaa ggccaggaaccgtaaaaaggccgcgttgctggcgtttttccataggctccgcccccctgacgagcatcacaaaaatcgacgctca agtcagaggtggcgaaacccgacaggactataaagataccaggcgtttccccctggaagctccctcgtgcgctctcctgttccgac cctgccgcttaccggatacctgtccgcctttctcccttcgggaagcgtggcgctttctcatagctcacgctgtaggtatctcagttcggtg taggtcgttcgctccaagctgggctgtgtgcacgaaccccccgttcagcccgaccgctgcgccttatccggtaactatcgtcttgagt ccaacccggtaagacacgacttatcgccactggcagcagccactggtaacaggattagcagagcgaggtatgtaggcggtgcta cagagttcttgaagtggtggcctaactacggctacactagaagaacagtatttggtatctgcgctctgctgaagccagttaccttcgg aaaaagagttggtagctcttgatccggcaaacaaaccaccgctggtagcggtttttttgtttgcaagcagcagattacgcgcagaaa aaaaggatctcaagaagatcctttgatcttttctacggggtctgacgctcagtggaacgaaaactcacgttaagggattttggtcatg agattatcaaaaaggatcttcacctagatccttttaaattaaaaatgaagttttaaatcaatctaaagtatatatgagtaaacttggtctg acagttaccaatgcttaatcagtgaggcacctatctcagcgatctgtctatttcgttcatccatagttgcctgactccccgtcgtgtagat aactacgatacgggagggcttaccatctggccccagtgctgcaatgataccgcgagaaccacgctcaccggctccagatttatca gcaataaaccagccagccggaagggccgagcgcagaagtggtcctgcaactttatccgcctccatccagtctattaattgttgccg ggaagctagagtaagtagttcgccagttaatagtttgcgcaacgttgttgccattgctacaggcatcgtggtgtcacgctcgtcgtttgg tatggcttcattcagctccggttcccaacgatcaaggcgagttacatgatcccccatgttgtgcaaaaaagcggttagctccttcggtc ctccgatcgttgtcagaagtaagttggccgcagtgttatcactcatggttatggcagcactgcataattctcttactgtcatgccatccgt aagatgcttttctgtgactggtgagtactcaaccaagtcattctgagaatagtgtatgcggcgaccgagttgctcttgcccggcgtcaa tacgggataataccgcgccacatagcagaactttaaaagtgctcatcattggaaaacgttcttcggggcgaaaactctcaaggatc ttaccgctgttgagatccagttcgatgtaacccactcgtgcacccaactgatcttcagcatcttttactttcaccagcgtttctgggtgagc aaaaacaggaaggcaaaatgccgcaaaaaagggaataagggcgacacggaaatgttgaatactcatactcttcctttttcaatat tattgaagcatttatcagggttattgtctcatgagcggatacatatttgaatgtatttagaaaaataaacaaataggggttccgcgcaca tttccccgaaaagtgccacctgacgtc(SEQ ID NO.109)
pLH-AAAA
ttggggttgcgccttttccaaggcagccctgggtttgcgcagggacgcggctgctctgggcgtggttccgggaaacgcagcggcgc cgaccctgggtctcgcacattcttcacgtccgttcgcagcgtcacccggatcttcgccgctacccttgtgggccccccggcgacgctt cctgctccgcccctaagtcgggaaggttccttgcggttcgcggcgtgccggacgtgacaaacggaagccgcacgtctcactagta ccctcgcagacggacagcgccagggagcaatggcagcgcgccgaccgcgatgggctgtggccaatagcggctgctcagcag ggcgcgccgagagcagcggccgggaaggggcggtgcgggaggcggggtgtggggcggtagtgtgggccctgttcctgcccg cgcggtgttccgcattctgcaagcctccggagcgcacgtcggcagtcggctccctcgttgaccgaatcaccgacctctctccccag ggggatccaccggatcaagcttgccagctggggcgccctctggtaaggttgggaagccctgcagatctgatcccggggggcaat gagatatgaaaaagcctgaactcaccgcgacgtctgtcgagaagtttctgatcgaaaagttcgacagcgtctccgacctgatgca gctctcggagggcgaagaatctcgtgctttcagcttcgatgtaggagggcgtggatatgtcctgcgggtaaatagctgcgccgatgg tttctacaaagatcgttatgtttatcggcactttgcatcggccgcgctcccgattccggaagtgcttgacattggggaatttagcgagag cctgacctattgcatctcccgccgtgcacagggtgtcacgttgcaagatctgcctgaaaccgaactgcccgctgttctgcagccggt cgcggaggccatggatgcgatcgctgcggccgatcttagccagacgagcgggttcggcccattcggaccgcaaggaatcggtc aatacactacatggcgtgatttcatatgcgcgattgctgatccccatgtgtatcactggcaaactgtgatggacgacaccgtcagtgc gtccgtcgcgcaggctctcgatgagctgatgctttgggccgaggactgccccgaagtccggcacctcgtgcacgcggatttcggct ccaacaatgtcctgacggacaatggccgcataacagcggtcattgactggagcgaggcgatgttcggggattcccaatacgagg tcgccaacatcttcttctggaggccgtggttggcttgtatggagcagcagacgcgctacttcgagcggaggcatccggagcttgcag gatcgccgcggctccgggcgtatatgctccgcattggtcttgaccaactctatcagagcttggttgacggcaatttcgatgatgcagct tgggcgcagggtcgatgcgacgcaatcgtccgatccggagccgggactgtcgggcgtacacaaatcgcccgcagaagcgcgg ccgtctggaccgatggctgtgtagaagtactcgccgatagtggaaaccgacgccccagcactcgtccgagggcaaaggaatag agtagatgccgaccgggatctatcgataccgtcgacctcgagggggggcccggtacctttaagaccaatgacttacaaggcagct gtagatcttagccactttttaaaagaaaaggggggactggaagggctaattcactcccaacgaagaaaagatctgctttttgcttgta ctgggtctctctggttagaccagatctgagcctgggagctctctggctaactagggaacccactgcttaagcctcaataaagcttgcc ttgagtgcttcaagtagtgtgtgcccgtctgttgtgtgactctggtaactagagatccctcagacccttttagtcagtgtggaaaatctcta gcagtagtagttcatgtcatcttattattcagtatttataacttgcaaagaaatgaatatcagagagtgagaggaacttgtttattgcagc ttataatggttacaaataaagcaatagcatcacaaatttcacaaataaagcatttttttcactgcattctagttgtggtttgtccaaactca tcaatgtatcttatcatgtctggctctagctatcccgcccctaactccgcccatcccgcccctaactccgcccagttccgcccattctcc gccccatggctgactaattttttttatttatgcagaggccgaggccgcctcggcctctgagctattccagaagtagtgaggaggctttttt ggaggcctagggacgtacccaattcgccctatagtgagtcgtattacgcgcgctcactggccgtcgttttacaacgtcgtgactggg aaaaccctggcgttacccaacttaatcgccttgcagcacatccccctttcgccagctggcgtaatagcgaagaggcccgcaccga tcgcccttcccaacagttgcgcagcctgaatggcgaatgggacgcgccctgtagcggcgcattaagcgcggcgggtgtggtggtt acgcgcagcgtgaccgctacacttgccagcgccctagcgcccgctcctttcgctttcttcccttcctttctcgccacgttcgccggctttc cccgtcaagctctaaatcgggggctccctttagggttccgatttagtgctttacggcacctcgaccccaaaaaacttgattagggtgat ggttcacgtagtgggccatcgccctgatagacggtttttcgccctttgacgttggagtccacgttctttaatagtggactcttgttccaaac tggaacaacactcaaccctatctcggtctattcttttgatttataagggattttgccgatttcggcctattggttaaaaaatgagctgattta acaaaaatttaacgcgaattttaacaaaatattaacgcttacaatttaggtggcacttttcggggaaatgtgcgcggaacccctatttg tttatttttctaaatacattcaaatatgtatccgctcatgagacaataaccctgataaatgcttcaataatattgaaaaaggaagagtatg agtattcaacatttccgtgtcgcccttattcccttttttgcggcattttgccttcctgtttttgctcacccagaaacgctggtgaaagtaaaag atgctgaagatcagttgggtgcacgagtgggttacatcgaactggatctcaacagcggtaagatccttgagagttttcgccccgaag aacgttttccaatgatgagcacttttaaagttctgctatgtggcgcggtattatcccgtattgacgccgggcaagagcaactcggtcgc cgcatacactattctcagaatgacttggttgagtactcaccagtcacagaaaagcatcttacggatggcatgacagtaagagaatta tgcagtgctgccataaccatgagtgataacactgcggccaacttacttctgacaacgatcggaggaccgaaggagctaaccgcttt tttgcacaacatgggggatcatgtaactcgccttgatcgttgggaaccggagctgaatgaagccataccaaacgacgagcgtgac accacgatgcctgtagcaatggcaacaacgttgcgcaaactattaactggcgaactacttactctagcttcccggcaacaattaata gactggatggaggcggataaagttgcaggaccacttctgcgctcggcccttccggctggctggtttattgctgataaatctggagcc ggtgagcgtgggtctcgcggtatcattgcagcactggggccagatggtaagccctcccgtatcgtagttatctacacgacggggag tcaggcaactatggatgaacgaaatagacagatcgctgagataggtgcctcactgattaagcattggtaactgtcagaccaagttt actcatatatactttagattgatttaaaacttcatttttaatttaaaaggatctaggtgaagatcctttttgataatctcatgaccaaaatccc ttaacgtgagttttcgttccactgagcgtcagaccccgtagaaaagatcaaaggatcttcttgagatcctttttttctgcgcgtaatctgct gcttgcaaacaaaaaaaccaccgctaccagcggtggtttgtttgccggatcaagagctaccaactctttttccgaaggtaactggctt cagcagagcgcagataccaaatactgttcttctagtgtagccgtagttaggccaccacttcaagaactctgtagcaccgcctacata cctcgctctgctaatcctgttaccagtggctgctgccagtggcgataagtcgtgtcttaccgggttggactcaagacgatagttaccgg ataaggcgcagcggtcgggctgaacggggggttcgtgcacacagcccagcttggagcgaacgacctacaccgaactgagata cctacagcgtgagctatgagaaagcgccacgcttcccgaagggagaaaggcggacaggtatccggtaagcggcagggtcgg aacaggagagcgcacgagggagcttccagggggaaacgcctggtatctttatagtcctgtcgggtttcgccacctctgacttgagc gtcgatttttgtgatgctcgtcaggggggcggagcctatggaaaaacgccagcaacgcggcctttttacggttcctggccttttgctgg ccttttgctcacatgttctttcctgcgttatcccctgattctgtggataaccgtattaccgcctttgagtgagctgataccgctcgccgcagc cgaacgaccgagcgcagcgagtcagtgagcgaggaagcggaagagcgcccaatacgcaaaccgcctctccccgcgcgttgg ccgattcattaatgcagctggcacgacaggtttcccgactggaaagcgggcagtgagcgcaacgcaattaatgtgagttagctca ctcattaggcaccccaggctttacactttatgcttccggctcgtatgttgtgtggaattgtgagcggataacaatttcacacaggaaac agctatgaccatgattacgccaagcgcgcaattaaccctcactaaagggaacaaaagctggagctgcaagcttaatgtagtcttat gcaatactcttgtagtcttgcaacatggtaacgatgagttagcaacatgccttacaaggagagaaaaagcaccgtgcatgccgatt ggtggaagtaaggtggtacgatcgtgccttattaggaaggcaacagacgggtctgacatggattggacgaaccactgaattgccg cattgcagagatattgtatttaagtgcctagctcgatacataaacgggtctctctggttagaccagatctgagcctgggagctctctgg ctaactagggaacccactgcttaagcctcaataaagcttgccttgagtgcttcaagtagtgtgtgcccgtctgttgtgtgactctggtaa ctagagatccctcagacccttttagtcagtgtggaaaatctctagcagtggcgcccgaacagggacttgaaagcgaaagggaaa ccagaggagctctctcgacgcaggactcggcttgctgaagcgcgcacggcaagaggcgaggggcggcgactggtgagtacgc caaaaattttgactagcggaggctagaaggagagagatgggtgcgagagcgtcagtattaagcgggggagaattagatcgcga tgggaaaaaattcggttaaggccagggggaaagaaaaaatataaattaaaacatatagtatgggcaagcagggagctagaac gattcgcagttaatcctggcctgttagaaacatcagaaggctgtagacaaatactgggacagctacaaccatcccttcagacagg atcagaagaacttagatcattatataatacagtagcaaccctctattgtgtgcatcaaaggatagagataaaagacaccaaggaa gctttagacaagatagaggaagagcaaaacaaaagtaagaccaccgcacagcaagcggccgctgatcttcagacctggagg aggagatatgagggacaattggagaagtgaattatataaatataaagtagtaaaaattgaaccattaggagtagcacccaccaa ggcaaagagaagagtggtgcagagagaaaaaagagcagtgggaataggagctttgttccttgggttcttgggagcagcaggaa gcactatgggcgcagcgtcaatgacgctgacggtacaggccagacaattattgtctggtatagtgcagcagcagaacaatttgctg agggctattgaggcgcaacagcatctgttgcaactcacagtctggggcatcaagcagctccaggcaagaatcctggctgtggaa agatacctaaaggatcaacagctcctggggatttggggttgctctggaaaactcatttgcaccactgctgtgccttggaatgctagttg gagtaataaatctctggaacagatttggaatcacacgacctggatggagtgggacagagaaattaacaattacacaagcttaata cactccttaattgaagaatcgcaaaaccagcaagaaaagaatgaacaagaattattggaattagataaatgggcaagtttgtgga attggtttaacataacaaattggctgtggtatataaaattattcataatgatagtaggaggcttggtaggtttaagaatagtttttgctgtac tttctatagtgaatagagttaggcagggatattcaccattatcgtttcagacccacctcccaaccccgaggggacccgacaggccc gaaggaatagaagaagaaggtggagagagagacagagacagatccattcgattagtgaacggatctcgacggtatcgatcac gagactagcctcgagcggccgcccccttcaccgagggcctatttcccatgattccttcatatttgcatatacgatacaaggctgttaga gagataattggaattaatttgactgtaaacacaaagatattagtacaaaatacgtgacgtagaaagtaataatttcttgggtagtttgc agttttaaaattatgttttaaaatggactatcatatgcttaccgtaacttgaaagtatttcgatttcttggctttatatatcttgtggaaaggac gaaacaccggtgtcttcgaggcttactaaaagccagataacagtatgcgtatttgcgcgctgatttttgcggtataagaatatatactg atatgtatacccgaagtatgtcaaaaagaggtgtgctatgaagcagcgtattacagtgacagttgacagcgacagctatcagttgct caaggcatatatgatgtcaatatctccggtctggtaagcacaaccatgcagaatgaagcccgtcgtctgcgtgccgaacgctggaa agcggaaaatcaggaagggatggctgaggtcgcccggtttattgaaatgaacggctcttttgctgacgagaacagggactggtga aatgcagtttaaggtttacacctataaaagagagagccgttatcgtctgtttgtggatgtacagagtgatattattgacacgcccgggc gacggatggtgatccccctggccagtgcacgtctgctgtcagataaagtctcccgtgaactttacccggtggtgcatatcggggatg aaagctggcgcatgatgaccaccgatatggccagtgtgccggtctccgttatcggggaagaagtggctgatctcagccaccgcga aaatgacatcaaaaacgccattaacctgatgttctggggaatataaaccctgcaggacgaagaccctttttttgaattctcgacctcg agacaaatggcagtattcatccacaattttaaaagaaaaggggggattggggggtacagtgcaggggaaagaatagtagacat aatagcaacagacatacaaactaaagaattacaaaaacaaattacaaaaattcaaaattttcgggtttattacagggacagcaga gatccactttggccgcggctcgaggggg(SEQ ID NO.110)
pLH-sgRNA3
ttggggttgcgccttttccaaggcagccctgggtttgcgcagggacgcggctgctctgggcgtggttccgggaaacgcagcggcgc cgaccctgggtctcgcacattcttcacgtccgttcgcagcgtcacccggatcttcgccgctacccttgtgggccccccggcgacgctt cctgctccgcccctaagtcgggaaggttccttgcggttcgcggcgtgccggacgtgacaaacggaagccgcacgtctcactagta ccctcgcagacggacagcgccagggagcaatggcagcgcgccgaccgcgatgggctgtggccaatagcggctgctcagcag ggcgcgccgagagcagcggccgggaaggggcggtgcgggaggcggggtgtggggcggtagtgtgggccctgttcctgcccg cgcggtgttccgcattctgcaagcctccggagcgcacgtcggcagtcggctccctcgttgaccgaatcaccgacctctctccccag ggggatccaccggatcaagcttgccagctggggcgccctctggtaaggttgggaagccctgcagatctgatcccggggggcaat gagatatgaaaaagcctgaactcaccgcgacgtctgtcgagaagtttctgatcgaaaagttcgacagcgtctccgacctgatgca gctctcggagggcgaagaatctcgtgctttcagcttcgatgtaggagggcgtggatatgtcctgcgggtaaatagctgcgccgatgg tttctacaaagatcgttatgtttatcggcactttgcatcggccgcgctcccgattccggaagtgcttgacattggggaatttagcgagag cctgacctattgcatctcccgccgtgcacagggtgtcacgttgcaagatctgcctgaaaccgaactgcccgctgttctgcagccggt cgcggaggccatggatgcgatcgctgcggccgatcttagccagacgagcgggttcggcccattcggaccgcaaggaatcggtc aatacactacatggcgtgatttcatatgcgcgattgctgatccccatgtgtatcactggcaaactgtgatggacgacaccgtcagtgc gtccgtcgcgcaggctctcgatgagctgatgctttgggccgaggactgccccgaagtccggcacctcgtgcacgcggatttcggct ccaacaatgtcctgacggacaatggccgcataacagcggtcattgactggagcgaggcgatgttcggggattcccaatacgagg tcgccaacatcttcttctggaggccgtggttggcttgtatggagcagcagacgcgctacttcgagcggaggcatccggagcttgcag gatcgccgcggctccgggcgtatatgctccgcattggtcttgaccaactctatcagagcttggttgacggcaatttcgatgatgcagct tgggcgcagggtcgatgcgacgcaatcgtccgatccggagccgggactgtcgggcgtacacaaatcgcccgcagaagcgcgg ccgtctggaccgatggctgtgtagaagtactcgccgatagtggaaaccgacgccccagcactcgtccgagggcaaaggaatag agtagatgccgaccgggatctatcgataccgtcgacctcgagggggggcccggtacctttaagaccaatgacttacaaggcagct gtagatcttagccactttttaaaagaaaaggggggactggaagggctaattcactcccaacgaagaaaagatctgctttttgcttgta ctgggtctctctggttagaccagatctgagcctgggagctctctggctaactagggaacccactgcttaagcctcaataaagcttgcc ttgagtgcttcaagtagtgtgtgcccgtctgttgtgtgactctggtaactagagatccctcagacccttttagtcagtgtggaaaatctcta gcagtagtagttcatgtcatcttattattcagtatttataacttgcaaagaaatgaatatcagagagtgagaggaacttgtttattgcagc ttataatggttacaaataaagcaatagcatcacaaatttcacaaataaagcatttttttcactgcattctagttgtggtttgtccaaactca tcaatgtatcttatcatgtctggctctagctatcccgcccctaactccgcccatcccgcccctaactccgcccagttccgcccattctcc gccccatggctgactaattttttttatttatgcagaggccgaggccgcctcggcctctgagctattccagaagtagtgaggaggctttttt ggaggcctagggacgtacccaattcgccctatagtgagtcgtattacgcgcgctcactggccgtcgttttacaacgtcgtgactggg aaaaccctggcgttacccaacttaatcgccttgcagcacatccccctttcgccagctggcgtaatagcgaagaggcccgcaccga tcgcccttcccaacagttgcgcagcctgaatggcgaatgggacgcgccctgtagcggcgcattaagcgcggcgggtgtggtggtt acgcgcagcgtgaccgctacacttgccagcgccctagcgcccgctcctttcgctttcttcccttcctttctcgccacgttcgccggctttc cccgtcaagctctaaatcgggggctccctttagggttccgatttagtgctttacggcacctcgaccccaaaaaacttgattagggtgat ggttcacgtagtgggccatcgccctgatagacggtttttcgccctttgacgttggagtccacgttctttaatagtggactcttgttccaaac tggaacaacactcaaccctatctcggtctattcttttgatttataagggattttgccgatttcggcctattggttaaaaaatgagctgattta acaaaaatttaacgcgaattttaacaaaatattaacgcttacaatttaggtggcacttttcggggaaatgtgcgcggaacccctatttg tttatttttctaaatacattcaaatatgtatccgctcatgagacaataaccctgataaatgcttcaataatattgaaaaaggaagagtatg agtattcaacatttccgtgtcgcccttattcccttttttgcggcattttgccttcctgtttttgctcacccagaaacgctggtgaaagtaaaag atgctgaagatcagttgggtgcacgagtgggttacatcgaactggatctcaacagcggtaagatccttgagagttttcgccccgaag aacgttttccaatgatgagcacttttaaagttctgctatgtggcgcggtattatcccgtattgacgccgggcaagagcaactcggtcgc cgcatacactattctcagaatgacttggttgagtactcaccagtcacagaaaagcatcttacggatggcatgacagtaagagaatta tgcagtgctgccataaccatgagtgataacactgcggccaacttacttctgacaacgatcggaggaccgaaggagctaaccgcttt tttgcacaacatgggggatcatgtaactcgccttgatcgttgggaaccggagctgaatgaagccataccaaacgacgagcgtgac accacgatgcctgtagcaatggcaacaacgttgcgcaaactattaactggcgaactacttactctagcttcccggcaacaattaata gactggatggaggcggataaagttgcaggaccacttctgcgctcggcccttccggctggctggtttattgctgataaatctggagcc ggtgagcgtgggtctcgcggtatcattgcagcactggggccagatggtaagccctcccgtatcgtagttatctacacgacggggag tcaggcaactatggatgaacgaaatagacagatcgctgagataggtgcctcactgattaagcattggtaactgtcagaccaagttt actcatatatactttagattgatttaaaacttcatttttaatttaaaaggatctaggtgaagatcctttttgataatctcatgaccaaaatccc ttaacgtgagttttcgttccactgagcgtcagaccccgtagaaaagatcaaaggatcttcttgagatcctttttttctgcgcgtaatctgct gcttgcaaacaaaaaaaccaccgctaccagcggtggtttgtttgccggatcaagagctaccaactctttttccgaaggtaactggctt cagcagagcgcagataccaaatactgttcttctagtgtagccgtagttaggccaccacttcaagaactctgtagcaccgcctacata cctcgctctgctaatcctgttaccagtggctgctgccagtggcgataagtcgtgtcttaccgggttggactcaagacgatagttaccgg ataaggcgcagcggtcgggctgaacggggggttcgtgcacacagcccagcttggagcgaacgacctacaccgaactgagata cctacagcgtgagctatgagaaagcgccacgcttcccgaagggagaaaggcggacaggtatccggtaagcggcagggtcgg aacaggagagcgcacgagggagcttccagggggaaacgcctggtatctttatagtcctgtcgggtttcgccacctctgacttgagc gtcgatttttgtgatgctcgtcaggggggcggagcctatggaaaaacgccagcaacgcggcctttttacggttcctggccttttgctgg ccttttgctcacatgttctttcctgcgttatcccctgattctgtggataaccgtattaccgcctttgagtgagctgataccgctcgccgcagc cgaacgaccgagcgcagcgagtcagtgagcgaggaagcggaagagcgcccaatacgcaaaccgcctctccccgcgcgttgg ccgattcattaatgcagctggcacgacaggtttcccgactggaaagcgggcagtgagcgcaacgcaattaatgtgagttagctca ctcattaggcaccccaggctttacactttatgcttccggctcgtatgttgtgtggaattgtgagcggataacaatttcacacaggaaac agctatgaccatgattacgccaagcgcgcaattaaccctcactaaagggaacaaaagctggagctgcaagcttaatgtagtcttat gcaatactcttgtagtcttgcaacatggtaacgatgagttagcaacatgccttacaaggagagaaaaagcaccgtgcatgccgatt ggtggaagtaaggtggtacgatcgtgccttattaggaaggcaacagacgggtctgacatggattggacgaaccactgaattgccg cattgcagagatattgtatttaagtgcctagctcgatacataaacgggtctctctggttagaccagatctgagcctgggagctctctgg ctaactagggaacccactgcttaagcctcaataaagcttgccttgagtgcttcaagtagtgtgtgcccgtctgttgtgtgactctggtaa ctagagatccctcagacccttttagtcagtgtggaaaatctctagcagtggcgcccgaacagggacttgaaagcgaaagggaaa ccagaggagctctctcgacgcaggactcggcttgctgaagcgcgcacggcaagaggcgaggggcggcgactggtgagtacgc caaaaattttgactagcggaggctagaaggagagagatgggtgcgagagcgtcagtattaagcgggggagaattagatcgcga tgggaaaaaattcggttaaggccagggggaaagaaaaaatataaattaaaacatatagtatgggcaagcagggagctagaac gattcgcagttaatcctggcctgttagaaacatcagaaggctgtagacaaatactgggacagctacaaccatcccttcagacagg atcagaagaacttagatcattatataatacagtagcaaccctctattgtgtgcatcaaaggatagagataaaagacaccaaggaa gctttagacaagatagaggaagagcaaaacaaaagtaagaccaccgcacagcaagcggccgctgatcttcagacctggagg aggagatatgagggacaattggagaagtgaattatataaatataaagtagtaaaaattgaaccattaggagtagcacccaccaa ggcaaagagaagagtggtgcagagagaaaaaagagcagtgggaataggagctttgttccttgggttcttgggagcagcaggaa gcactatgggcgcagcgtcaatgacgctgacggtacaggccagacaattattgtctggtatagtgcagcagcagaacaatttgctg agggctattgaggcgcaacagcatctgttgcaactcacagtctggggcatcaagcagctccaggcaagaatcctggctgtggaa agatacctaaaggatcaacagctcctggggatttggggttgctctggaaaactcatttgcaccactgctgtgccttggaatgctagttg gagtaataaatctctggaacagatttggaatcacacgacctggatggagtgggacagagaaattaacaattacacaagcttaata cactccttaattgaagaatcgcaaaaccagcaagaaaagaatgaacaagaattattggaattagataaatgggcaagtttgtgga attggtttaacataacaaattggctgtggtatataaaattattcataatgatagtaggaggcttggtaggtttaagaatagtttttgctgtac tttctatagtgaatagagttaggcagggatattcaccattatcgtttcagacccacctcccaaccccgaggggacccgacaggccc gaaggaatagaagaagaaggtggagagagagacagagacagatccattcgattagtgaacggatctcgacggtatcgatcac gagactagcctcgagcggccgcccccttcaccgagggcctatttcccatgattccttcatatttgcatatacgatacaaggctgttaga gagataattggaattaatttgactgtaaacacaaagatattagtacaaaatacgtgacgtagaaagtaataatttcttgggtagtttgc agttttaaaattatgttttaaaatggactatcatatgcttaccgtaacttgaaagtatttcgatttcttggctttatatatcttgtggaaaggac gaaacaccggtgtcttcgaggcttactaaaagccagataacagtatgcgtatttgcgcgctgatttttgcggtataagaatatatactg atatgtatacccgaagtatgtcaaaaagaggtgtgctatgaagcagcgtattacagtgacagttgacagcgacagctatcagttgct caaggcatatatgatgtcaatatctccggtctggtaagcacaaccatgcagaatgaagcccgtcgtctgcgtgccgaacgctggaa agcggaaaatcaggaagggatggctgaggtcgcccggtttattgaaatgaacggctcttttgctgacgagaacagggactggtga aatgcagtttaaggtttacacctataaaagagagagccgttatcgtctgtttgtggatgtacagagtgatattattgacacgcccgggc gacggatggtgatccccctggccagtgcacgtctgctgtcagataaagtctcccgtgaactttacccggtggtgcatatcggggatg aaagctggcgcatgatgaccaccgatatggccagtgtgccggtctccgttatcggggaagaagtggctgatctcagccaccgcga aaatgacatcaaaaacgccattaacctgatgttctggggaatataaaccctgcaggacgaagacccgttttagagctagaaatag caagttaaaataaggctagtccgttatcaacttgaaaaagtggcaccgagtcggtgctttttttgaattctcgacctcgagacaaatgg cagtattcatccacaattttaaaagaaaaggggggattggggggtacagtgcaggggaaagaatagtagacataatagcaaca gacatacaaactaaagaattacaaaaacaaattacaaaaattcaaaattttcgggtttattacagggacagcagagatccactttg gccgcggctcgaggggg(SEQ ID NO.111)
pCMV-FKBP-MCP
acggatcgggagatctaccggtacgcgttgacagagacgggatccgacattgattattgactagttattaatagtaatcaattacgg ggtcattagttcatagcccatatatggagttccgcgttacataacttacggtaaatggcccgcctggctgaccgcccaacgaccccc gcccattgacgtcaataatgacgtatgttcccatagtaacgccaatagggactttccattgacgtcaatgggtggagtatttacggtaa actgcccacttggcagtacatcaagtgtatcatatgccaagtacgccccctattgacgtcaatgacggtaaatggcccgcctggcat tatgcccagtacatgaccttatgggactttcctacttggcagtacatctacgtattagtcatcgctattaccatggtgatgcggttttggca gtacatcaatgggcgtggatagcggtttgactcacggggatttccaagtctccaccccattgacgtcaatgggagtttgttttggcacc aaaatcaacgggactttccaaaatgtcgtaacaactccgccccattgacgcaaatgggcggtaggcgtgtacggtgggaggtcta tataagcagagctggtttagtgaaccgtcagatccgctagagatccgcggccgctaatacgactcactatagggagagccgccac catgggagtgcaggtggaaaccatctccccaggagacgggcgcaccttccccaagcgcggccagacctgcgtggtgcactaca ccgggatgcttgaagatggaaagaaatttgattcctctcgggacagaaacaagccctttaagtttatgctaggcaagcaggaggtg atccgaggctgggaagaaggggttgcccagatgagtgtgggtcagagagccaaactgactatatctccagattatgcctatggtgc cactgggcacccaggcatcatcccaccacatgccactctcgtcttcgatgtggagcttctaaaactggaaaaacggacagccgac ggaagcgagttcgagtcaccaaagaagaagcggaaagtcatggcttctaactttactcagttcgttctcgtcgacaatggcggaac tggcgacgtgactgttgccccaagcaacttcgctaacgggatcgctgaatggatcagctctaactcgcgttcacaggcttacaaagt aacctgtagcgttcgtcagagctctgcgcagaatcgcaaatacaccatcaaagtcgaggtgcctaaaggcgcctggcgttcgtact taaatatggaactaaccattccaattttcgccacgaattccgactgcgagcttattgttaaggcaatgcaaggtctcctaaaagatgg aaacccgattccctcagcaatcgcagcaaactccggcatctacgagggcagaggaagtcttctaacatgcggtgacgtggagga gaatcccggccctgctagcggtactagcatggcagaaatcggtactggctttccattcgacccccattatgtggaagtcctgggcga gcgcatgcactacgtcgatgttggtccgcgcgatggcacccctgtgctgttcctgcacggtaacccgacctcctcctacgtgtggcgc aacatcatcccgcatgttgcaccgacccatcgctgcattgctccagacctgatcggtatgggcaaatccgacaaaccagacctgg gttatttcttcgacgaccacgtccgcttcatggatgccttcatcgaagccctgggtctggaagaggtcgtcctggtcattcacgactgg ggctccgctctgggtttccactgggccaagcgcaatccagagcgcgtcaaaggtattgcatttatggagttcatccgccctatcccga cctgggacgaatggccagaatttgcccgcgagaccttccaggccttccgcaccaccgacgtcggccgcaagctgatcatcgatc agaacgtttttatcgagggtacgctgccgatgggtgtcgtccgcccgctgactgaagtcgagatggaccattaccgcgagccgttcc tgaatcctgttgaccgcgagccactgtggcgcttcccaaacgagctgccaatcgccggtgagccagcgaacatcgtcgcgctggt cgaagaatacatggactggctgcaccagtcccctgtcccgaagctgctgttctggggcaccccaggcgttctgatcccaccggcc gaagccgctcgcctggccaaaagcctgcctaactgcaaggctgtggacatcggcccgggtctgaatctgctgcaagaagacaa cccggacctgatcggcagcgagatcgcgcgctggctgtcgacgctggagatttccggctaagtttaaacccgctgatcagcctcga ctgtgccttctagttgccagccatctgttgtttgcccctcccccgtgccttccttgaccctggaaggtgccactcccactgtcctttcctaat aaaatgagaaaattgcatcgcattgtctgagtaggtgtcattctattctggggggtggggtggggcaggacagcaagggggagga ttgggaagacaatagcaggcatgctggggatgcggtgggctctatgggcggccgcgaattcacatgtgagcaaaaggccagca aaaggccaggaaccgtaaaaaggccgcgttgctggcgtttttccataggctccgcccccctgacgagcatcacaaaaatcgacg ctcaagtcagaggtggcgaaacccgacaggactataaagataccaggcgtttccccctggaagctccctcgtgcgctctcctgttc cgaccctgccgcttaccggatacctgtccgcctttctcccttcgggaagcgtggcgctttctcatagctcacgctgtaggtatctcagttc ggtgtaggtcgttcgctccaagctgggctgtgtgcacgaaccccccgttcagcccgaccgctgcgccttatccggtaactatcgtctt gagtccaacccggtaagacacgacttatcgccactggcagcagccactggtaacaggattagcagagcgaggtatgtaggcgg tgctacagagttcttgaagtggtggcctaactacggctacactagaagaacagtatttggtatctgcgctctgctgaagccagttacct tcggaaaaagagttggtagctcttgatccggcaaacaaaccaccgctggtagcggtttttttgtttgcaagcagcagattacgcgca gaaaaaaaggatctcaagaagatcctttgatcttttctacggggtctgacgctcagtggaacgaaaactcacgttaagggattttggt catgagattatcaaaaaggatcttcacctagatccttttaaattaaaaatgaagttttaaatcaatctaaagtatatatgagtaaacttg gtctgacagttaccaatgcttaatcagtgaggcacctatctcagcgatctgtctatttcgttcatccatagttgcctgactccccgtcgtgt agataactacgatacgggagggcttaccatctggccccagtgctgcaatgataccgcgagaaccacgctcaccggctccagattt atcagcaataaaccagccagccggaagggccgagcgcagaagtggtcctgcaactttatccgcctccatccagtctattaattgtt gccgggaagctagagtaagtagttcgccagttaatagtttgcgcaacgttgttgccattgctacaggcatcgtggtgtcacgctcgtc gtttggtatggcttcattcagctccggttcccaacgatcaaggcgagttacatgatcccccatgttgtgcaaaaaagcggttagctcctt cggtcctccgatcgttgtcagaagtaagttggccgcagtgttatcactcatggttatggcagcactgcataattctcttactgtcatgcca tccgtaagatgcttttctgtgactggtgagtactcaaccaagtcattctgagaatagtgtatgcggcgaccgagttgctcttgcccggc gtcaatacgggataataccgcgccacatagcagaactttaaaagtgctcatcattggaaaacgttcttcggggcgaaaactctcaa ggatcttaccgctgttgagatccagttcgatgtaacccactcgtgcacccaactgatcttcagcatcttttactttcaccagcgtttctggg tgagcaaaaacaggaaggcaaaatgccgcaaaaaagggaataagggcgacacggaaatgttgaatactcatactcttccttttt caatattattgaagcatttatcagggttattgtctcatgagcggatacatatttgaatgtatttagaaaaataaacaaataggggttccg cgcacatttccccgaaaagtgccacctgacgtc(SEQ ID NO.112)
pCMV-PYL1-MCP
acggatcgggagatctaccggtacgcgttgacagagacgggatccgacattgattattgactagttattaatagtaatcaattacgg ggtcattagttcatagcccatatatggagttccgcgttacataacttacggtaaatggcccgcctggctgaccgcccaacgaccccc gcccattgacgtcaataatgacgtatgttcccatagtaacgccaatagggactttccattgacgtcaatgggtggagtatttacggtaa actgcccacttggcagtacatcaagtgtatcatatgccaagtacgccccctattgacgtcaatgacggtaaatggcccgcctggcat tatgcccagtacatgaccttatgggactttcctacttggcagtacatctacgtattagtcatcgctattaccatggtgatgcggttttggca gtacatcaatgggcgtggatagcggtttgactcacggggatttccaagtctccaccccattgacgtcaatgggagtttgttttggcacc aaaatcaacgggactttccaaaatgtcgtaacaactccgccccattgacgcaaatgggcggtaggcgtgtacggtgggaggtcta tataagcagagctggtttagtgaaccgtcagatccgctagagatccgcggccgctaatacgactcactatagggagagccgccac cggtgggggcgcgccaactcaagacgaattcacccaactctcccaatcaatcgccgagttccacacgtaccaactcggtaacgg ccgttgctcatctctcctagctcagcgaatccacgcgccgccggaaacagtatggtccgtggtgagacgtttcgataggccacagat ttacaaacacttcatcaaaagctgtaacgtgagtgaagatttcgagatgcgagtgggatgcacgcgcgacgtgaacgtgataagt ggattaccggcgaatacgtctcgagagagattagatctgttggacgatgatcggagagtgactgggtttagtataaccggtggtgaa cataggctgaggaattataaatcggttacgacggttcatagatttgagaaagaagaagaagaagaaaggatctggaccgttgtttt ggaatcttatgttgttgatgtaccggaaggtaattcggaggaagatacgagattgtttgctgatacggttattagattgaatcttcagaa acttgcttcgatcactgaagctatgaacaaacggacagccgacggaagcgagttcgagtcaccaaagaagaagcggaaagtc atggcttctaactttactcagttcgttctcgtcgacaatggcggaactggcgacgtgactgttgccccaagcaacttcgctaacgggat cgctgaatggatcagctctaactcgcgttcacaggcttacaaagtaacctgtagcgttcgtcagagctctgcgcagaatcgcaaata caccatcaaagtcgaggtgcctaaaggcgcctggcgttcgtacttaaatatggaactaaccattccaattttcgccacgaattccga ctgcgagcttattgttaaggcaatgcaaggtctcctaaaagatggaaacccgattccctcagcaatcgcagcaaactccggcatct acgagggcagaggaagtcttctaacatgcggtgacgtggaggagaatcccggccctgctagcggtactagcatggcagaaatc ggtactggctttccattcgacccccattatgtggaagtcctgggcgagcgcatgcactacgtcgatgttggtccgcgcgatggcaccc ctgtgctgttcctgcacggtaacccgacctcctcctacgtgtggcgcaacatcatcccgcatgttgcaccgacccatcgctgcattgct ccagacctgatcggtatgggcaaatccgacaaaccagacctgggttatttcttcgacgaccacgtccgcttcatggatgccttcatcg aagccctgggtctggaagaggtcgtcctggtcattcacgactggggctccgctctgggtttccactgggccaagcgcaatccagag cgcgtcaaaggtattgcatttatggagttcatccgccctatcccgacctgggacgaatggccagaatttgcccgcgagaccttccag gccttccgcaccaccgacgtcggccgcaagctgatcatcgatcagaacgtttttatcgagggtacgctgccgatgggtgtcgtccgc ccgctgactgaagtcgagatggaccattaccgcgagccgttcctgaatcctgttgaccgcgagccactgtggcgcttcccaaacga gctgccaatcgccggtgagccagcgaacatcgtcgcgctggtcgaagaatacatggactggctgcaccagtcccctgtcccgaa gctgctgttctggggcaccccaggcgttctgatcccaccggccgaagccgctcgcctggccaaaagcctgcctaactgcaaggct gtggacatcggcccgggtctgaatctgctgcaagaagacaacccggacctgatcggcagcgagatcgcgcgctggctgtcgac gctggagatttccggctaagtttaaacccgctgatcagcctcgactgtgccttctagttgccagccatctgttgtttgcccctcccccgtg ccttccttgaccctggaaggtgccactcccactgtcctttcctaataaaatgagaaaattgcatcgcattgtctgagtaggtgtcattcta ttctggggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctggggatgcggtgggctc tatgggcggccgcgaattcacatgtgagcaaaaggccagcaaaaggccaggaaccgtaaaaaggccgcgttgctggcgtttttc cataggctccgcccccctgacgagcatcacaaaaatcgacgctcaagtcagaggtggcgaaacccgacaggactataaagat accaggcgtttccccctggaagctccctcgtgcgctctcctgttccgaccctgccgcttaccggatacctgtccgcctttctcccttcgg gaagcgtggcgctttctcatagctcacgctgtaggtatctcagttcggtgtaggtcgttcgctccaagctgggctgtgtgcacgaaccc cccgttcagcccgaccgctgcgccttatccggtaactatcgtcttgagtccaacccggtaagacacgacttatcgccactggcagca gccactggtaacaggattagcagagcgaggtatgtaggcggtgctacagagttcttgaagtggtggcctaactacggctacactag aagaacagtatttggtatctgcgctctgctgaagccagttaccttcggaaaaagagttggtagctcttgatccggcaaacaaaccac cgctggtagcggtttttttgtttgcaagcagcagattacgcgcagaaaaaaaggatctcaagaagatcctttgatcttttctacggggtc tgacgctcagtggaacgaaaactcacgttaagggattttggtcatgagattatcaaaaaggatcttcacctagatccttttaaattaaa aatgaagttttaaatcaatctaaagtatatatgagtaaacttggtctgacagttaccaatgcttaatcagtgaggcacctatctcagcg atctgtctatttcgttcatccatagttgcctgactccccgtcgtgtagataactacgatacgggagggcttaccatctggccccagtgct gcaatgataccgcgagaaccacgctcaccggctccagatttatcagcaataaaccagccagccggaagggccgagcgcaga agtggtcctgcaactttatccgcctccatccagtctattaattgttgccgggaagctagagtaagtagttcgccagttaatagtttgcgc aacgttgttgccattgctacaggcatcgtggtgtcacgctcgtcgtttggtatggcttcattcagctccggttcccaacgatcaaggcga gttacatgatcccccatgttgtgcaaaaaagcggttagctccttcggtcctccgatcgttgtcagaagtaagttggccgcagtgttatca ctcatggttatggcagcactgcataattctcttactgtcatgccatccgtaagatgcttttctgtgactggtgagtactcaaccaagtcatt ctgagaatagtgtatgcggcgaccgagttgctcttgcccggcgtcaatacgggataataccgcgccacatagcagaactttaaaa gtgctcatcattggaaaacgttcttcggggcgaaaactctcaaggatcttaccgctgttgagatccagttcgatgtaacccactcgtgc acccaactgatcttcagcatcttttactttcaccagcgtttctgggtgagcaaaaacaggaaggcaaaatgccgcaaaaaaggga ataagggcgacacggaaatgttgaatactcatactcttcctttttcaatattattgaagcatttatcagggttattgtctcatgagcggata catatttgaatgtatttagaaaaataaacaaataggggttccgcgcacatttccccgaaaagtgccacctgacgtc(SEQ ID NO.113)
pCMV-FRB-PE2-T2A-GFP
gacattgattattgactagttattaatagtaatcaattacggggtcattagttcatagcccatatatggagttccgcgttacataacttacg gtaaatggcccgcctggctgaccgcccaacgacccccgcccattgacgtcaataatgacgtatgttcccatagtaacgccaatag ggactttccattgacgtcaatgggtggagtatttacggtaaactgcccacttggcagtacatcaagtgtatcatatgccaagtacgcc ccctattgacgtcaatgacggtaaatggcccgcctggcattatgcccagtacatgaccttatgggactttcctacttggcagtacatct acgtattagtcatcgctattaccatggtgatgcggttttggcagtacatcaatgggcgtggatagcggtttgactcacggggatttccaa gtctccaccccattgacgtcaatgggagtttgttttggcaccaaaatcaacgggactttccaaaatgtcgtaacaactccgccccatt gacgcaaatgggcggtaggcgtgtacggtgggaggtctatataagcagagctggtttagtgaaccgtcagatccgctagagatcc gcggccgctaatacgactcactatagggagagccgccaccatgatcctctggcatgagatgtggcatgaaggcctggaagaggc atctcgtttgtactttggggaaaggaacgtgaaaggcatgtttgaggtgctggagcccttgcatgctatgatggaacggggacccca gactctgaaggaaacatcctttaatcaggcctatggtcgagatttaatggaggcccaagagtggtgcaggaagtacatgaaatca gggaatgtcaaggacctcacccaagcctgggacctctattatcatgtgttccgacgaatctcaaagaaacggacagccgacgga agcgagttcgagtcaccaaagaagaagcggaaagtcgacaagaagtacagcatcggcctggacatcggcaccaactctgtgg gctgggccgtgatcaccgacgagtacaaggtgcccagcaagaaattcaaggtgctgggcaacaccgaccggcacagcatcaa gaagaacctgatcggagccctgctgttcgacagcggcgaaacagccgaggccacccggctgaagagaaccgccagaagaa gatacaccagacggaagaaccggatctgctatctgcaagagatcttcagcaacgagatggccaaggtggacgacagcttcttcc acagactggaagagtccttcctggtggaagaggataagaagcacgagcggcaccccatcttcggcaacatcgtggacgaggtg gcctaccacgagaagtaccccaccatctaccacctgagaaagaaactggtggacagcaccgacaaggccgacctgcggctga tctatctggccctggcccacatgatcaagttccggggccacttcctgatcgagggcgacctgaaccccgacaacagcgacgtgga caagctgttcatccagctggtgcagacctacaaccagctgttcgaggaaaaccccatcaacgccagcggcgtggacgccaagg ccatcctgtctgccagactgagcaagagcagacggctggaaaatctgatcgcccagctgcccggcgagaagaagaatggcctg ttcggaaacctgattgccctgagcctgggcctgacccccaacttcaagagcaacttcgacctggccgaggatgccaaactgcagc tgagcaaggacacctacgacgacgacctggacaacctgctggcccagatcggcgaccagtacgccgacctgtttctggccgcc aagaacctgtccgacgccatcctgctgagcgacatcctgagagtgaacaccgagatcaccaaggcccccctgagcgcctctatg atcaagagatacgacgagcaccaccaggacctgaccctgctgaaagctctcgtgcggcagcagctgcctgagaagtacaaag agattttcttcgaccagagcaagaacggctacgccggctacattgacggcggagccagccaggaagagttctacaagttcatcaa gcccatcctggaaaagatggacggcaccgaggaactgctcgtgaagctgaacagagaggacctgctgcggaagcagcggac cttcgacaacggcagcatcccccaccagatccacctgggagagctgcacgccattctgcggcggcaggaagatttttacccattc ctgaaggacaaccgggaaaagatcgagaagatcctgaccttccgcatcccctactacgtgggccctctggccaggggaaacag cagattcgcctggatgaccagaaagagcgaggaaaccatcaccccctggaacttcgaggaagtggtggacaagggcgcttccg cccagagcttcatcgagcggatgaccaacttcgataagaacctgcccaacgagaaggtgctgcccaagcacagcctgctgtacg agtacttcaccgtgtataacgagctgaccaaagtgaaatacgtgaccgagggaatgagaaagcccgccttcctgagcggcgag cagaaaaaggccatcgtggacctgctgttcaagaccaaccggaaagtgaccgtgaagcagctgaaagaggactacttcaaga aaatcgagtgcttcgactccgtggaaatctccggcgtggaagatcggttcaacgcctccctgggcacataccacgatctgctgaaa attatcaaggacaaggacttcctggacaatgaggaaaacgaggacattctggaagatatcgtgctgaccctgacactgtttgagg acagagagatgatcgaggaacggctgaaaacctatgcccacctgttcgacgacaaagtgatgaagcagctgaagcggcggag atacaccggctggggcaggctgagccggaagctgatcaacggcatccgggacaagcagtccggcaagacaatcctggatttcc tgaagtccgacggcttcgccaacagaaacttcatgcagctgatccacgacgacagcctgacctttaaagaggacatccagaaag cccaggtgtccggccagggcgatagcctgcacgagcacattgccaatctggccggcagccccgccattaagaagggcatcctg cagacagtgaaggtggtggacgagctcgtgaaagtgatgggccggcacaagcccgagaacatcgtgatcgaaatggccagag agaaccagaccacccagaagggacagaagaacagccgcgagagaatgaagcggatcgaagagggcatcaaagagctgg gcagccagatcctgaaagaacaccccgtggaaaacacccagctgcagaacgagaagctgtacctgtactacctgcagaatgg gcgggatatgtacgtggaccaggaactggacatcaaccggctgtccgactacgatgtggacgctatcgtgcctcagagctttctga aggacgactccatcgacaacaaggtgctgaccagaagcgacaagaaccggggcaagagcgacaacgtgccctccgaagag gtcgtgaagaagatgaagaactactggcggcagctgctgaacgccaagctgattacccagagaaagttcgacaatctgaccaa ggccgagagaggcggcctgagcgaactggataaggccggcttcatcaagagacagctggtggaaacccggcagatcacaaa gcacgtggcacagatcctggactcccggatgaacactaagtacgacgagaatgacaagctgatccgggaagtgaaagtgatca ccctgaagtccaagctggtgtccgatttccggaaggatttccagttttacaaagtgcgcgagatcaacaactaccaccacgcccac gacgcctacctgaacgccgtcgtgggaaccgccctgatcaaaaagtaccctaagctggaaagcgagttcgtgtacggcgactac aaggtgtacgacgtgcggaagatgatcgccaagagcgagcaggaaatcggcaaggctaccgccaagtacttcttctacagcaa catcatgaactttttcaagaccgagattaccctggccaacggcgagatccggaagcggcctctgatcgagacaaacggcgaaac cggggagatcgtgtgggataagggccgggattttgccaccgtgcggaaagtgctgagcatgccccaagtgaatatcgtgaaaaa gaccgaggtgcagacaggcggcttcagcaaagagtctatcctgcccaagaggaacagcgataagctgatcgccagaaagaa ggactgggaccctaagaagtacggcggcttcgacagccccaccgtggcctattctgtgctggtggtggccaaagtggaaaaggg caagtccaagaaactgaagagtgtgaaagagctgctggggatcaccatcatggaaagaagcagcttcgagaagaatcccatcg actttctggaagccaagggctacaaagaagtgaaaaaggacctgatcatcaagctgcctaagtactccctgttcgagctggaaaa cggccggaagagaatgctggcctctgccggcgaactgcagaagggaaacgaactggccctgccctccaaatatgtgaacttcct gtacctggccagccactatgagaagctgaagggctcccccgaggataatgagcagaaacagctgtttgtggaacagcacaagc actacctggacgagatcatcgagcagatcagcgagttctccaagagagtgatcctggccgacgctaatctggacaaagtgctgtc cgcctacaacaagcaccgggataagcccatcagagagcaggccgagaatatcatccacctgtttaccctgaccaatctgggagc ccctgccgccttcaagtactttgacaccaccatcgaccggaagaggtacaccagcaccaaagaggtgctggacgccaccctgat ccaccagagcatcaccggcctgtacgagacacggatcgacctgtctcagctgggaggtgactctggaggatctagcggaggatc ctctggcagcgagacaccaggaacaagcgagtcagcaacaccagagagcagtggcggcagcagcggcggcagcagcacc ctaaatatagaagatgagtatcggctacatgagacctcaaaagagccagatgtttctctagggtccacatggctgtctgattttcctca ggcctgggcggaaaccgggggcatgggactggcagttcgccaagctcctctgatcatacctctgaaagcaacctctacccccgtg tccataaaacaataccccatgtcacaagaagccagactggggatcaagccccacatacagagactgttggaccagggaatact ggtaccctgccagtccccctggaacacgcccctgctacccgttaagaaaccagggactaatgattataggcctgtccaggatctga gagaagtcaacaagcgggtggaagacatccaccccaccgtgcccaacccttacaacctcttgagcgggctcccaccgtcccac cagtggtacactgtgcttgatttaaaggatgcctttttctgcctgagactccaccccaccagtcagcctctcttcgcctttgagtggaga gatccagagatgggaatctcaggacaattgacctggaccagactcccacagggtttcaaaaacagtcccaccctgtttaatgagg cactgcacagagacctagcagacttccggatccagcacccagacttgatcctgctacagtacgtggatgacttactgctggccgcc acttctgagctagactgccaacaaggtactcgggccctgttacaaaccctagggaacctcgggtatcgggcctcggccaagaaa gcccaaatttgccagaaacaggtcaagtatctggggtatcttctaaaagagggtcagagatggctgactgaggccagaaaagag actgtgatggggcagcctactccgaagacccctcgacaactaagggagttcctagggaaggcaggcttctgtcgcctcttcatccct gggtttgcagaaatggcagcccccctgtaccctctcaccaaaccggggactctgtttaattggggcccagaccaacaaaaggcct atcaagaaatcaagcaagctcttctaactgccccagccctggggttgccagatttgactaagccctttgaactctttgtcgacgagaa gcagggctacgccaaaggtgtcctaacgcaaaaactgggaccttggcgtcggccggtggcctacctgtccaaaaagctagacc cagtagcagctgggtggcccccttgcctacggatggtagcagccattgccgtactgacaaaggatgcaggcaagctaaccatgg gacagccactagtcattctggccccccatgcagtagaggcactagtcaaacaaccccccgaccgctggctttccaacgcccggat gactcactatcaggccttgcttttggacacggaccgggtccagttcggaccggtggtagccctgaacccggctacgctgctcccact gcctgaggaagggctgcaacacaactgccttgatatcctggccgaagcccacggaacccgacccgacctaacggaccagccg ctcccagacgccgaccacacctggtacacggatggaagcagtctcttacaagagggacagcgtaaggcgggagctgcggtga ccaccgagaccgaggtaatctgggctaaagccctgccagccgggacatccgctcagcgggctgaactgatagcactcacccag gccctaaagatggcagaaggtaagaagctaaatgtttatactgatagccgttatgcttttgctactgcccatatccatggagaaatat acagaaggcgtgggtggctcacatcagaaggcaaagagatcaaaaataaagacgagatcttggccctactaaaagccctctttc tgcccaaaagacttagcataatccattgtccaggacatcaaaagggacacagcgccgaggctagaggcaaccggatggctgac caagcggcccgaaaggcagccatcacagagactccagacacctctaccctcctcatagaaaattcatcaccctctggcggctca aaaagaaccgccgacggcagcgaattcgagcccaagaagaagaggaaagtcgagggcagaggaagtcttctaacatgcggt gacgtggaggagaatcccggccctgctagcggtactagcatgcgtaaaggcgaagagctgttcactggtgtcgtccctattctggt ggaactggatggtgatgtcaacggtcataagttttccgtgcgtggcgagggtgaaggtgacgcaactaatggtaaactgacgctga agttcatctgtactactggtaaactgccggtaccttggccgactctggtaacgacgctgacttatggtgttcagtgctttgctcgttatccg gaccatatgaagcagcatgacttcttcaagtccgccatgccggaaggctatgtgcaggaacgcacgatttcctttaaggatgacgg cacgtacaaaacgcgtgcggaagtgaaatttgaaggcgataccctggtaaaccgcattgagctgaaaggcattgactttaaaga agacggcaatatcctgggccataagctggaatacaattttaacagccacaatgtttacatcaccgccgataaacaaaaaaatggc attaaagcgaattttaaaattcgccacaacgtggaggatggcagcgtgcagctggctgatcactaccagcaaaacactccaatcg gtgatggtcctgttctgctgccagacaatcactatctgagcacgcaaagcgttctgtctaaagatccgaacgagaaacgcgatcata tggttctgctggagttcgtaaccgcagcgggcatcacgcatggtatggatgaactgtacaaataagtttaaacccgctgatcagcct cgactgtgccttctagttgccagccatctgttgtttgcccctcccccgtgccttccttgaccctggaaggtgccactcccactgtcctttcct aataaaatgagaaaattgcatcgcattgtctgagtaggtgtcattctattctggggggtggggtggggcaggacagcaaggggga ggattgggaagacaatagcaggcatgctggggatgcggtgggctctatggcttctgaggcggaaagaaccagctggggctcgat accgtcgacctctagctagagcttggcgtaatcatggtcatagctgtttcctgtgtgaaattgttatccgctcacaattccacacaacat acgagccggaagcataaagtgtaaagcctagggtgcctaatgagtgagctaactcacattaattgcgttgcgctcactgcccgcttt ccagtcgggaaacctgtcgtgccagctgcattaatgaatcggccaacgcgcggggagaggcggtttgcgtattgggcgctcttccg cttcctcgctcactgactcgctgcgctcggtcgttcggctgcggcgagcggtatcagctcactcaaaggcggtaatacggttatccac agaatcaggggataacgcaggaaagaacatgtgagcaaaaggccagcaaaaggccaggaaccgtaaaaaggccgcgttg ctggcgtttttccataggctccgcccccctgacgagcatcacaaaaatcgacgctcaagtcagaggtggcgaaacccgacagga ctataaagataccaggcgtttccccctggaagctccctcgtgcgctctcctgttccgaccctgccgcttaccggatacctgtccgccttt ctcccttcgggaagcgtggcgctttctcatagctcacgctgtaggtatctcagttcggtgtaggtcgttcgctccaagctgggctgtgtg cacgaaccccccgttcagcccgaccgctgcgccttatccggtaactatcgtcttgagtccaacccggtaagacacgacttatcgcc actggcagcagccactggtaacaggattagcagagcgaggtatgtaggcggtgctacagagttcttgaagtggtggcctaactac ggctacactagaagaacagtatttggtatctgcgctctgctgaagccagttaccttcggaaaaagagttggtagctcttgatccggca aacaaaccaccgctggtagcggtggtttttttgtttgcaagcagcagattacgcgcagaaaaaaaggatctcaagaagatcctttga tcttttctacggggtctgacactcagtggaacgaaaactcacgttaagggattttggtcatgagattatcaaaaaggatcttcacctag atccttttaaattaaaaatgaagttttaaatcaatctaaagtatatatgagtaaacttggtctgacagttaccaatgcttaatcagtgagg cacctatctcagcgatctgtctatttcgttcatccatagttgcctgactccccgtcgtgtagataactacgatacgggagggcttaccatc tggccccagtgctgcaatgataccgcgagacccacgctcaccggctccagatttatcagcaataaaccagccagccggaaggg ccgagcgcagaagtggtcctgcaactttatccgcctccatccagtctattaattgttgccgggaagctagagtaagtagttcgccagtt aatagtttgcgcaacgttgttgccattgctacaggcatcgtggtgtcacgctcgtcgtttggtatggcttcattcagctccggttcccaac gatcaaggcgagttacatgatcccccatgttgtgcaaaaaagcggttagctccttcggtcctccgatcgttgtcagaagtaagttggc cgcagtgttatcactcatggttatggcagcactgcataattctcttactgtcatgccatccgtaagatgcttttctgtgactggtgagtactc aaccaagtcattctgagaatagtgtatgcggcgaccgagttgctcttgcccggcgtcaatacgggataataccgcgccacatagca gaactttaaaagtgctcatcattggaaaacgttcttcggggcgaaaactctcaaggatcttaccgctgttgagatccagttcgatgtaa cccactcgtgcacccaactgatcttcagcatcttttactttcaccagcgtttctgggtgagcaaaaacaggaaggcaaaatgccgca aaaaagggaataagggcgacacggaaatgttgaatactcatactcttcctttttcaatattattgaagcatttatcagggttattgtctca tgagcggatacatatttgaatgtatttagaaaaataaacaaataggggttccgcgcacatttccccgaaaagtgccacctgacgtcg acggatcgggagatcgatctcccgatcccctagggtctactctcagtacaatctgctctgatgccgcatagttaagccagtatctgctc cctgcttgtgtgttggaggtcgctgagtagtgcgcgagcaaaatttaagctacaacaaggcaaggcttgaccgacaattgcatgaa gaatctgcttagggttaggcgttttgcgctgcttcgcgatgtacgggccagatatacgcgtt(SEQ ID NO.114)
pCMV-ABI-PE2-T2A-GFP
gacattgattattgactagttattaatagtaatcaattacggggtcattagttcatagcccatatatggagttccgcgttacataacttacg gtaaatggcccgcctggctgaccgcccaacgacccccgcccattgacgtcaataatgacgtatgttcccatagtaacgccaatag ggactttccattgacgtcaatgggtggagtatttacggtaaactgcccacttggcagtacatcaagtgtatcatatgccaagtacgcc ccctattgacgtcaatgacggtaaatggcccgcctggcattatgcccagtacatgaccttatgggactttcctacttggcagtacatct acgtattagtcatcgctattaccatggtgatgcggttttggcagtacatcaatgggcgtggatagcggtttgactcacggggatttccaa gtctccaccccattgacgtcaatgggagtttgttttggcaccaaaatcaacgggactttccaaaatgtcgtaacaactccgccccatt gacgcaaatgggcggtaggcgtgtacggtgggaggtctatataagcagagctggtttagtgaaccgtcagatccgctagagatcc gcggccgctaatacgactcactatagggagagccgccaccatgacgcgtgtgcctttgtatggttttacttcgatttgtggaagaaga cctgagatggaagctgctgtttcgactataccaagattccttcaatcttcctctggttcgatgttagatggtcggtttgatcctcaatccgc cgctcatttcttcggtgtttacgacggccatggcggttctcaggtagcgaactattgtagagagaggatgcatttggctttggcggagg agatagctaaggagaaaccgatgctctgcgatggtgatacgtggctggagaagtggaagaaagctcttttcaactcgttcctgaga gttgactcggagattgagtcagttgcgccggagacggttgggtcaacgtcggtggttgccgttgttttcccgtctcacatcttcgtcgcta actgcggtgactctagagccgttctttgccgcggcaaaactgcacttccattatccgttgaccataaaccggatagagaagatgaag ctgcgaggattgaagccgcaggagggaaagtgattcagtggaatggagctcgtgttttcggtgttctcgccatgtcgagatccattg gcgatagatacttgaaaccatccatcattcctgatccggaagtgacggctgtgaagagagtaaaagaagatgattgtctgattttgg cgagtgacggggtttgggatgtaatgacggatgaagaagcgtgtgagatggcaaggaagcggattctcttgtggcacaagaaaa acgcggtggctggggatgcatcgttgctcgcggatgagcggagaaaggaagggaaagatcctgcggcgatgtccgcggctgag tatttgtcaaagctggcgatacagagaggaagcaaagacaacataagtgtggtggtggttgatttgaagaaacggacagccgac ggaagcgagttcgagtcaccaaagaagaagcggaaagtcgacaagaagtacagcatcggcctggacatcggcaccaactct gtgggctgggccgtgatcaccgacgagtacaaggtgcccagcaagaaattcaaggtgctgggcaacaccgaccggcacagca tcaagaagaacctgatcggagccctgctgttcgacagcggcgaaacagccgaggccacccggctgaagagaaccgccagaa gaagatacaccagacggaagaaccggatctgctatctgcaagagatcttcagcaacgagatggccaaggtggacgacagcttc ttccacagactggaagagtccttcctggtggaagaggataagaagcacgagcggcaccccatcttcggcaacatcgtggacgag gtggcctaccacgagaagtaccccaccatctaccacctgagaaagaaactggtggacagcaccgacaaggccgacctgcggc tgatctatctggccctggcccacatgatcaagttccggggccacttcctgatcgagggcgacctgaaccccgacaacagcgacgt ggacaagctgttcatccagctggtgcagacctacaaccagctgttcgaggaaaaccccatcaacgccagcggcgtggacgcca aggccatcctgtctgccagactgagcaagagcagacggctggaaaatctgatcgcccagctgcccggcgagaagaagaatgg cctgttcggaaacctgattgccctgagcctgggcctgacccccaacttcaagagcaacttcgacctggccgaggatgccaaactg cagctgagcaaggacacctacgacgacgacctggacaacctgctggcccagatcggcgaccagtacgccgacctgtttctggc cgccaagaacctgtccgacgccatcctgctgagcgacatcctgagagtgaacaccgagatcaccaaggcccccctgagcgcct ctatgatcaagagatacgacgagcaccaccaggacctgaccctgctgaaagctctcgtgcggcagcagctgcctgagaagtac aaagagattttcttcgaccagagcaagaacggctacgccggctacattgacggcggagccagccaggaagagttctacaagttc atcaagcccatcctggaaaagatggacggcaccgaggaactgctcgtgaagctgaacagagaggacctgctgcggaagcag cggaccttcgacaacggcagcatcccccaccagatccacctgggagagctgcacgccattctgcggcggcaggaagatttttac ccattcctgaaggacaaccgggaaaagatcgagaagatcctgaccttccgcatcccctactacgtgggccctctggccagggga aacagcagattcgcctggatgaccagaaagagcgaggaaaccatcaccccctggaacttcgaggaagtggtggacaagggc gcttccgcccagagcttcatcgagcggatgaccaacttcgataagaacctgcccaacgagaaggtgctgcccaagcacagcctg ctgtacgagtacttcaccgtgtataacgagctgaccaaagtgaaatacgtgaccgagggaatgagaaagcccgccttcctgagc ggcgagcagaaaaaggccatcgtggacctgctgttcaagaccaaccggaaagtgaccgtgaagcagctgaaagaggactact tcaagaaaatcgagtgcttcgactccgtggaaatctccggcgtggaagatcggttcaacgcctccctgggcacataccacgatctg ctgaaaattatcaaggacaaggacttcctggacaatgaggaaaacgaggacattctggaagatatcgtgctgaccctgacactgtt tgaggacagagagatgatcgaggaacggctgaaaacctatgcccacctgttcgacgacaaagtgatgaagcagctgaagcgg cggagatacaccggctggggcaggctgagccggaagctgatcaacggcatccgggacaagcagtccggcaagacaatcctg gatttcctgaagtccgacggcttcgccaacagaaacttcatgcagctgatccacgacgacagcctgacctttaaagaggacatcc agaaagcccaggtgtccggccagggcgatagcctgcacgagcacattgccaatctggccggcagccccgccattaagaaggg catcctgcagacagtgaaggtggtggacgagctcgtgaaagtgatgggccggcacaagcccgagaacatcgtgatcgaaatgg ccagagagaaccagaccacccagaagggacagaagaacagccgcgagagaatgaagcggatcgaagagggcatcaaag agctgggcagccagatcctgaaagaacaccccgtggaaaacacccagctgcagaacgagaagctgtacctgtactacctgca gaatgggcgggatatgtacgtggaccaggaactggacatcaaccggctgtccgactacgatgtggacgctatcgtgcctcagag ctttctgaaggacgactccatcgacaacaaggtgctgaccagaagcgacaagaaccggggcaagagcgacaacgtgccctcc gaagaggtcgtgaagaagatgaagaactactggcggcagctgctgaacgccaagctgattacccagagaaagttcgacaatct gaccaaggccgagagaggcggcctgagcgaactggataaggccggcttcatcaagagacagctggtggaaacccggcagat cacaaagcacgtggcacagatcctggactcccggatgaacactaagtacgacgagaatgacaagctgatccgggaagtgaaa gtgatcaccctgaagtccaagctggtgtccgatttccggaaggatttccagttttacaaagtgcgcgagatcaacaactaccaccac gcccacgacgcctacctgaacgccgtcgtgggaaccgccctgatcaaaaagtaccctaagctggaaagcgagttcgtgtacggc gactacaaggtgtacgacgtgcggaagatgatcgccaagagcgagcaggaaatcggcaaggctaccgccaagtacttcttcta cagcaacatcatgaactttttcaagaccgagattaccctggccaacggcgagatccggaagcggcctctgatcgagacaaacgg cgaaaccggggagatcgtgtgggataagggccgggattttgccaccgtgcggaaagtgctgagcatgccccaagtgaatatcgt gaaaaagaccgaggtgcagacaggcggcttcagcaaagagtctatcctgcccaagaggaacagcgataagctgatcgccag aaagaaggactgggaccctaagaagtacggcggcttcgacagccccaccgtggcctattctgtgctggtggtggccaaagtgga aaagggcaagtccaagaaactgaagagtgtgaaagagctgctggggatcaccatcatggaaagaagcagcttcgagaagaat cccatcgactttctggaagccaagggctacaaagaagtgaaaaaggacctgatcatcaagctgcctaagtactccctgttcgagct ggaaaacggccggaagagaatgctggcctctgccggcgaactgcagaagggaaacgaactggccctgccctccaaatatgtg aacttcctgtacctggccagccactatgagaagctgaagggctcccccgaggataatgagcagaaacagctgtttgtggaacagc acaagcactacctggacgagatcatcgagcagatcagcgagttctccaagagagtgatcctggccgacgctaatctggacaaag tgctgtccgcctacaacaagcaccgggataagcccatcagagagcaggccgagaatatcatccacctgtttaccctgaccaatct gggagcccctgccgccttcaagtactttgacaccaccatcgaccggaagaggtacaccagcaccaaagaggtgctggacgcca ccctgatccaccagagcatcaccggcctgtacgagacacggatcgacctgtctcagctgggaggtgactctggaggatctagcg gaggatcctctggcagcgagacaccaggaacaagcgagtcagcaacaccagagagcagtggcggcagcagcggcggcag cagcaccctaaatatagaagatgagtatcggctacatgagacctcaaaagagccagatgtttctctagggtccacatggctgtctg attttcctcaggcctgggcggaaaccgggggcatgggactggcagttcgccaagctcctctgatcatacctctgaaagcaacctct acccccgtgtccataaaacaataccccatgtcacaagaagccagactggggatcaagccccacatacagagactgttggacca gggaatactggtaccctgccagtccccctggaacacgcccctgctacccgttaagaaaccagggactaatgattataggcctgtcc aggatctgagagaagtcaacaagcgggtggaagacatccaccccaccgtgcccaacccttacaacctcttgagcgggctccca ccgtcccaccagtggtacactgtgcttgatttaaaggatgcctttttctgcctgagactccaccccaccagtcagcctctcttcgcctttg agtggagagatccagagatgggaatctcaggacaattgacctggaccagactcccacagggtttcaaaaacagtcccaccctgtt taatgaggcactgcacagagacctagcagacttccggatccagcacccagacttgatcctgctacagtacgtggatgacttactgc tggccgccacttctgagctagactgccaacaaggtactcgggccctgttacaaaccctagggaacctcgggtatcgggcctcggc caagaaagcccaaatttgccagaaacaggtcaagtatctggggtatcttctaaaagagggtcagagatggctgactgaggccag aaaagagactgtgatggggcagcctactccgaagacccctcgacaactaagggagttcctagggaaggcaggcttctgtcgcct cttcatccctgggtttgcagaaatggcagcccccctgtaccctctcaccaaaccggggactctgtttaattggggcccagaccaaca aaaggcctatcaagaaatcaagcaagctcttctaactgccccagccctggggttgccagatttgactaagccctttgaactctttgtc gacgagaagcagggctacgccaaaggtgtcctaacgcaaaaactgggaccttggcgtcggccggtggcctacctgtccaaaaa gctagacccagtagcagctgggtggcccccttgcctacggatggtagcagccattgccgtactgacaaaggatgcaggcaagct aaccatgggacagccactagtcattctggccccccatgcagtagaggcactagtcaaacaaccccccgaccgctggctttccaac gcccggatgactcactatcaggccttgcttttggacacggaccgggtccagttcggaccggtggtagccctgaacccggctacgct gctcccactgcctgaggaagggctgcaacacaactgccttgatatcctggccgaagcccacggaacccgacccgacctaacgg accagccgctcccagacgccgaccacacctggtacacggatggaagcagtctcttacaagagggacagcgtaaggcgggag ctgcggtgaccaccgagaccgaggtaatctgggctaaagccctgccagccgggacatccgctcagcgggctgaactgatagca ctcacccaggccctaaagatggcagaaggtaagaagctaaatgtttatactgatagccgttatgcttttgctactgcccatatccatg gagaaatatacagaaggcgtgggtggctcacatcagaaggcaaagagatcaaaaataaagacgagatcttggccctactaaa agccctctttctgcccaaaagacttagcataatccattgtccaggacatcaaaagggacacagcgccgaggctagaggcaaccg gatggctgaccaagcggcccgaaaggcagccatcacagagactccagacacctctaccctcctcatagaaaattcatcaccctc tggcggctcaaaaagaaccgccgacggcagcgaattcgagcccaagaagaagaggaaagtcgagggcagaggaagtcttct aacatgcggtgacgtggaggagaatcccggccctgctagcggtactagcatgcgtaaaggcgaagagctgttcactggtgtcgtc cctattctggtggaactggatggtgatgtcaacggtcataagttttccgtgcgtggcgagggtgaaggtgacgcaactaatggtaaa ctgacgctgaagttcatctgtactactggtaaactgccggtaccttggccgactctggtaacgacgctgacttatggtgttcagtgctttg ctcgttatccggaccatatgaagcagcatgacttcttcaagtccgccatgccggaaggctatgtgcaggaacgcacgatttcctttaa ggatgacggcacgtacaaaacgcgtgcggaagtgaaatttgaaggcgataccctggtaaaccgcattgagctgaaaggcattg actttaaagaagacggcaatatcctgggccataagctggaatacaattttaacagccacaatgtttacatcaccgccgataaacaa aaaaatggcattaaagcgaattttaaaattcgccacaacgtggaggatggcagcgtgcagctggctgatcactaccagcaaaac actccaatcggtgatggtcctgttctgctgccagacaatcactatctgagcacgcaaagcgttctgtctaaagatccgaacgagaaa cgcgatcatatggttctgctggagttcgtaaccgcagcgggcatcacgcatggtatggatgaactgtacaaataagtttaaacccgc tgatcagcctcgactgtgccttctagttgccagccatctgttgtttgcccctcccccgtgccttccttgaccctggaaggtgccactccca ctgtcctttcctaataaaatgagaaaattgcatcgcattgtctgagtaggtgtcattctattctggggggtggggtggggcaggacagc aagggggaggattgggaagacaatagcaggcatgctggggatgcggtgggctctatggcttctgaggcggaaagaaccagctg gggctcgataccgtcgacctctagctagagcttggcgtaatcatggtcatagctgtttcctgtgtgaaattgttatccgctcacaattcca cacaacatacgagccggaagcataaagtgtaaagcctagggtgcctaatgagtgagctaactcacattaattgcgttgcgctcact gcccgctttccagtcgggaaacctgtcgtgccagctgcattaatgaatcggccaacgcgcggggagaggcggtttgcgtattgggc gctcttccgcttcctcgctcactgactcgctgcgctcggtcgttcggctgcggcgagcggtatcagctcactcaaaggcggtaatacg gttatccacagaatcaggggataacgcaggaaagaacatgtgagcaaaaggccagcaaaaggccaggaaccgtaaaaagg ccgcgttgctggcgtttttccataggctccgcccccctgacgagcatcacaaaaatcgacgctcaagtcagaggtggcgaaaccc gacaggactataaagataccaggcgtttccccctggaagctccctcgtgcgctctcctgttccgaccctgccgcttaccggatacctg tccgcctttctcccttcgggaagcgtggcgctttctcatagctcacgctgtaggtatctcagttcggtgtaggtcgttcgctccaagctgg gctgtgtgcacgaaccccccgttcagcccgaccgctgcgccttatccggtaactatcgtcttgagtccaacccggtaagacacgact tatcgccactggcagcagccactggtaacaggattagcagagcgaggtatgtaggcggtgctacagagttcttgaagtggtggcct aactacggctacactagaagaacagtatttggtatctgcgctctgctgaagccagttaccttcggaaaaagagttggtagctcttgat ccggcaaacaaaccaccgctggtagcggtggtttttttgtttgcaagcagcagattacgcgcagaaaaaaaggatctcaagaaga tcctttgatcttttctacggggtctgacactcagtggaacgaaaactcacgttaagggattttggtcatgagattatcaaaaaggatcttc acctagatccttttaaattaaaaatgaagttttaaatcaatctaaagtatatatgagtaaacttggtctgacagttaccaatgcttaatca gtgaggcacctatctcagcgatctgtctatttcgttcatccatagttgcctgactccccgtcgtgtagataactacgatacgggagggct taccatctggccccagtgctgcaatgataccgcgagacccacgctcaccggctccagatttatcagcaataaaccagccagccg gaagggccgagcgcagaagtggtcctgcaactttatccgcctccatccagtctattaattgttgccgggaagctagagtaagtagtt cgccagttaatagtttgcgcaacgttgttgccattgctacaggcatcgtggtgtcacgctcgtcgtttggtatggcttcattcagctccggt tcccaacgatcaaggcgagttacatgatcccccatgttgtgcaaaaaagcggttagctccttcggtcctccgatcgttgtcagaagta agttggccgcagtgttatcactcatggttatggcagcactgcataattctcttactgtcatgccatccgtaagatgcttttctgtgactggt gagtactcaaccaagtcattctgagaatagtgtatgcggcgaccgagttgctcttgcccggcgtcaatacgggataataccgcgcc acatagcagaactttaaaagtgctcatcattggaaaacgttcttcggggcgaaaactctcaaggatcttaccgctgttgagatccagt tcgatgtaacccactcgtgcacccaactgatcttcagcatcttttactttcaccagcgtttctgggtgagcaaaaacaggaaggcaaa atgccgcaaaaaagggaataagggcgacacggaaatgttgaatactcatactcttcctttttcaatattattgaagcatttatcagggt tattgtctcatgagcggatacatatttgaatgtatttagaaaaataaacaaataggggttccgcgcacatttccccgaaaagtgccac ctgacgtcgacggatcgggagatcgatctcccgatcccctagggtctactctcagtacaatctgctctgatgccgcatagttaagcca gtatctgctccctgcttgtgtgttggaggtcgctgagtagtgcgcgagcaaaatttaagctacaacaaggcaaggcttgaccgacaa ttgcatgaagaatctgcttagggttaggcgttttgcgctgcttcgcgatgtacgggccagatatacgcgtt(SEQ ID NO.115)
Complement sequence 2
MCP
Atggcttctaactttactcagttcgttctcgtcgacaatggcggaactggcgacgtgactgttgccccaagcaacttcgctaacgggat cgctgaatggatcagctctaactcgcgttcacaggcttacaaagtaacctgtagcgttcgtcagagctctgcgcagaatcgcaaata caccatcaaagtcgaggtgcctaaaggcgcctggcgttcgtacttaaatatggaactaaccattccaattttcgccacgaattccga ctgcgagcttattgttaaggcaatgcaaggtctcctaaaagatggaaacccgattccctcagcaatcgcagcaaactccggcatct ac(SEQ ID NO.116)
tdMCP
gcttctaactttactcagttcgttctcgtcgacaatggcggaactggcgacgtgactgtcgccccaagcaacttcgctaacgggatcg ctgaatggatcagctctaactcgcgttcacaggcttacaaagtaacctgtagcgttcgtcagagctctgcgcagaatcgcaaataca ccatcaaagtcgaggtgcctaaaggcgcctggcgttcgtacttaaatatggaactaaccattccaattttcgccacgaattccgactg cgagcttattgttaaggcaatgcaaggtctcctaaaagatggaaacccgattccctcagcaatcgcagcaaactccggcatctacg ccatggccagcaacttcacccagttcgtgctggtggacaacggcggcaccggcgacgtgaccgtggcccccagcaacttcgcca acggcatcgccgagtggatcagcagcaacagcagaagccaggcctacaaggtgacctgcagcgtgagacagagcagcgcc cagaacagaaagtacaccatcaaggtggaggtgcccaagggcgcctggagaagctacctgaacatggagctgaccatcccca tcttcgccaccaacagcgactgcgagctgatcgtgaaggccatgcagggcctgctgaaggacggcaaccccatccccagcgcc atcgccgccaacagcggcatctacgcc(SEQ ID NO.117)
COM
ggtagtatgaaatcaattcgctgtaaaaactgcaacaaactgttatttaaggcggatagttttgatcacattgaaatcaggtgtccgcg ttgcaaacgtcacatcataatgctgaatgcctgcgagcatcccacggagaaacattgtgggaaaagagaaaaaatcacgcattct gacgaaaccgtgcgttatggctccactagtgggcacaagcttaatggcggtggcggagggatggatgctaagtcactaactgcct ggtcc(SEQ ID NO.118)
Csy4H29A
atggaccactacctcgacattcgcttgcgaccggacccggaatttcccccggcgcaactcatgagcgtgctcttcggcaagctcgc ccaggccctggtggcacagggcggggacaggatcggcgtgagcttccccgacctcgacgaaagccgctcccggctgggcgag cgcctgcgcattcatgcctcggcggacgaccttcgtgccctgctcgcccggccctggctggaagggttgcgggaccatctgcaattc ggagaaccggcagtcgtgcctcaccccacaccgtaccgtcaggtcagtcgggttcaggcgaaaagcaatccggaacgcctgcg gcggcggctcatgcgccggcacgatctgagtgaggaggaggctcggaaacgcattcccgatacggtcgcgagagccttggacc tgcccttcgtcacgctacgcagccagagcaccggacagcacttccgtctcttcatccgccacgggccgttgcaggtgacggcaga ggaaggaggattcacctgttacgggttgagcaaaggaggtttcgttccctggttc(SEQ ID NO.119)
PCP
Atgggttccaaaaccatcgttctttcggtcggcgaggctactcgcactctgactgagatccagtccaccgcagaccgtcagatcttc gaagagaaggtcgggcctctggtgggtcggctgcgcctcacggcttcgctccgtcaaaacggagccaagaccgcgtatcgcgtc aacctaaaactggatcaggcggacgtcgttgattccggacttccgaaagtgcgctacactcaggtatggtcgcacgacgtgacaat cgttgcgaatagcaccgaggcctcgcgcaaatcgttgtacgatttgaccaagtccctcgtcgcgacctcgcaggtcgaagatcttgt cgtcaaccttgtgccgctgggccgt(SEQ ID NO.120)
tdPCP
tccaaaactatcgttctgagcgtaggtgaagcgaccagaacgttaactgaaattcaatctacagcagacaggcaaatatttgaaga gaaagtcggtccattagtagggaggttaagattgacagctagcttaagacaaaatggagctaaaactgcatacagggtcaatttaa aattggatcaagcagatgtcgttgatagcggtctacctaaggttagatacacgcaagtgtggtcacacgatgtcactattgtcgcgaa ttctaccgaagctagtagaaaatcattgtatgatttaacaaaatccttggtggctacctctcaggtggaagatcttgttgtgaatttagttc cattaggtagggcggacccgctagcctccaaaaccatcgttctttcggtcggcgaggctactcgcactctgactgagatccagtcca ccgcagaccgtcagatcttcgaagagaaggtcgggcctctggtgggtcggctgcgcctcacggcttcgctccgtcaaaacggagc caagaccgcgtatcgcgtcaacctaaaactggatcaggcggacgtcgttgattccggacttccgaaagtgcgctacactcaggtat ggtcgcacgacgtgacaatcgttgcgaatagcaccgaggcctcgcgcaaatcgttgtacgatttgaccaagtccctcgtcgcgacc tcgcaggtcgaagatcttgtcgtcaaccttgtgccgctgggccgt(SEQ ID NO.121)
Sequence listing
<110> Shanghai university of science and technology
<120> an adjustable pilot editor and use thereof
<160> 121
<170> SIPOSequenceListing 1.0
<210> 1
<211> 19
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 1
acatgaggat cacccatgt 19
<210> 2
<211> 25
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 2
ggagcagacg atatggcgtc gctcc 25
<210> 3
<211> 19
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 3
ctgaatgcct gcgagcatc 19
<210> 4
<211> 24
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 4
actgccgtat aggcagctaa gaaa 24
<210> 5
<211> 17
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 5
ggccctgaag aagggcc 17
<210> 6
<211> 117
<212> PRT
<213> Artificial sequence (Artificial Sequence)
<400> 6
Met Ala Ser Asn Phe Thr Gln Phe Val Leu Val Asp Asn Gly Gly Thr
1 5 10 15
Gly Asp Val Thr Val Ala Pro Ser Asn Phe Ala Asn Gly Ile Ala Glu
20 25 30
Trp Ile Ser Ser Asn Ser Arg Ser Gln Ala Tyr Lys Val Thr Cys Ser
35 40 45
Val Arg Gln Ser Ser Ala Gln Asn Arg Lys Tyr Thr Ile Lys Val Glu
50 55 60
Val Pro Lys Gly Ala Trp Arg Ser Tyr Leu Asn Met Glu Leu Thr Ile
65 70 75 80
Pro Ile Phe Ala Thr Asn Ser Asp Cys Glu Leu Ile Val Lys Ala Met
85 90 95
Gln Gly Leu Leu Lys Asp Gly Asn Pro Ile Pro Ser Ala Ile Ala Ala
100 105 110
Asn Ser Gly Ile Tyr
115
<210> 7
<211> 123
<212> PRT
<213> Artificial sequence (Artificial Sequence)
<400> 7
Met Gly Ser Lys Thr Ile Val Leu Ser Val Gly Glu Ala Thr Arg Thr
1 5 10 15
Leu Thr Glu Ile Gln Ser Thr Ala Asp Arg Gln Ile Phe Glu Glu Lys
20 25 30
Val Gly Pro Leu Val Gly Arg Leu Arg Leu Thr Ala Ser Leu Arg Gln
35 40 45
Asn Gly Ala Lys Thr Ala Tyr Arg Val Asn Leu Lys Leu Asp Gln Ala
50 55 60
Asp Val Val Asp Ser Gly Leu Pro Lys Val Arg Tyr Thr Gln Val Trp
65 70 75 80
Ser His Asp Val Thr Ile Val Ala Asn Ser Thr Glu Ala Ser Arg Lys
85 90 95
Ser Leu Tyr Asp Leu Thr Lys Ser Leu Val Ala Thr Ser Gln Val Glu
100 105 110
Asp Leu Val Val Asn Leu Val Pro Leu Gly Arg
115 120
<210> 8
<211> 88
<212> PRT
<213> Artificial sequence (Artificial Sequence)
<400> 8
Gly Ser Met Lys Ser Ile Arg Cys Lys Asn Cys Asn Lys Leu Leu Phe
1 5 10 15
Lys Ala Asp Ser Phe Asp His Ile Glu Ile Arg Cys Pro Arg Cys Lys
20 25 30
Arg His Ile Ile Met Leu Asn Ala Cys Glu His Pro Thr Glu Lys His
35 40 45
Cys Gly Lys Arg Glu Lys Ile Thr His Ser Asp Glu Thr Val Arg Tyr
50 55 60
Gly Ser Thr Ser Gly His Lys Leu Asn Gly Gly Gly Gly Gly Met Asp
65 70 75 80
Ala Lys Ser Leu Thr Ala Trp Ser
85
<210> 9
<211> 187
<212> PRT
<213> Artificial sequence (Artificial Sequence)
<400> 9
Met Asp His Tyr Leu Asp Ile Arg Leu Arg Pro Asp Pro Glu Phe Pro
1 5 10 15
Pro Ala Gln Leu Met Ser Val Leu Phe Gly Lys Leu Ala Gln Ala Leu
20 25 30
Val Ala Gln Gly Gly Asp Arg Ile Gly Val Ser Phe Pro Asp Leu Asp
35 40 45
Glu Ser Arg Ser Arg Leu Gly Glu Arg Leu Arg Ile His Ala Ser Ala
50 55 60
Asp Asp Leu Arg Ala Leu Leu Ala Arg Pro Trp Leu Glu Gly Leu Arg
65 70 75 80
Asp His Leu Gln Phe Gly Glu Pro Ala Val Val Pro His Pro Thr Pro
85 90 95
Tyr Arg Gln Val Ser Arg Val Gln Ala Lys Ser Asn Pro Glu Arg Leu
100 105 110
Arg Arg Arg Leu Met Arg Arg His Asp Leu Ser Glu Glu Glu Ala Arg
115 120 125
Lys Arg Ile Pro Asp Thr Val Ala Arg Ala Leu Asp Leu Pro Phe Val
130 135 140
Thr Leu Arg Ser Gln Ser Thr Gly Gln His Phe Arg Leu Phe Ile Arg
145 150 155 160
His Gly Pro Leu Gln Val Thr Ala Glu Glu Gly Gly Phe Thr Cys Tyr
165 170 175
Gly Leu Ser Lys Gly Gly Phe Val Pro Trp Phe
180 185
<210> 10
<211> 22
<212> PRT
<213> Artificial sequence (Artificial Sequence)
<400> 10
Gly Asn Ala Arg Thr Arg Arg Arg Glu Arg Arg Ala Glu Lys Gln Ala
1 5 10 15
Gln Trp Lys Ala Ala Asn
20
<210> 11
<211> 317
<212> PRT
<213> Artificial sequence (Artificial Sequence)
<400> 11
Gly Gly Gly Ala Pro Thr Gln Asp Glu Phe Thr Gln Leu Ser Gln Ser
1 5 10 15
Ile Ala Glu Phe His Thr Tyr Gln Leu Gly Asn Gly Arg Cys Ser Ser
20 25 30
Leu Leu Ala Gln Arg Ile His Ala Pro Pro Glu Thr Val Trp Ser Val
35 40 45
Val Arg Arg Phe Asp Arg Pro Gln Ile Tyr Lys His Phe Ile Lys Ser
50 55 60
Cys Asn Val Ser Glu Asp Phe Glu Met Arg Val Gly Cys Thr Arg Asp
65 70 75 80
Val Asn Val Ile Ser Gly Leu Pro Ala Asn Thr Ser Arg Glu Arg Leu
85 90 95
Asp Leu Leu Asp Asp Asp Arg Arg Val Thr Gly Phe Ser Ile Thr Gly
100 105 110
Gly Glu His Arg Leu Arg Asn Tyr Lys Ser Val Thr Thr Val His Arg
115 120 125
Phe Glu Lys Glu Glu Glu Glu Glu Arg Ile Trp Thr Val Val Leu Glu
130 135 140
Ser Tyr Val Val Asp Val Pro Glu Gly Asn Ser Glu Glu Asp Thr Arg
145 150 155 160
Leu Phe Ala Asp Thr Val Ile Arg Leu Asn Leu Gln Lys Leu Ala Ser
165 170 175
Ile Thr Glu Ala Met Asn Lys Arg Thr Ala Asp Gly Ser Glu Phe Glu
180 185 190
Ser Pro Lys Lys Lys Arg Lys Val Met Ala Ser Asn Phe Thr Gln Phe
195 200 205
Val Leu Val Asp Asn Gly Gly Thr Gly Asp Val Thr Val Ala Pro Ser
210 215 220
Asn Phe Ala Asn Gly Ile Ala Glu Trp Ile Ser Ser Asn Ser Arg Ser
225 230 235 240
Gln Ala Tyr Lys Val Thr Cys Ser Val Arg Gln Ser Ser Ala Gln Asn
245 250 255
Arg Lys Tyr Thr Ile Lys Val Glu Val Pro Lys Gly Ala Trp Arg Ser
260 265 270
Tyr Leu Asn Met Glu Leu Thr Ile Pro Ile Phe Ala Thr Asn Ser Asp
275 280 285
Cys Glu Leu Ile Val Lys Ala Met Gln Gly Leu Leu Lys Asp Gly Asn
290 295 300
Pro Ile Pro Ser Ala Ile Ala Ala Asn Ser Gly Ile Tyr
305 310 315
<210> 12
<211> 300
<212> PRT
<213> Artificial sequence (Artificial Sequence)
<400> 12
Thr Arg Val Pro Leu Tyr Gly Phe Thr Ser Ile Cys Gly Arg Arg Pro
1 5 10 15
Glu Met Glu Ala Ala Val Ser Thr Ile Pro Arg Phe Leu Gln Ser Ser
20 25 30
Ser Gly Ser Met Leu Asp Gly Arg Phe Asp Pro Gln Ser Ala Ala His
35 40 45
Phe Phe Gly Val Tyr Asp Gly His Gly Gly Ser Gln Val Ala Asn Tyr
50 55 60
Cys Arg Glu Arg Met His Leu Ala Leu Ala Glu Glu Ile Ala Lys Glu
65 70 75 80
Lys Pro Met Leu Cys Asp Gly Asp Thr Trp Leu Glu Lys Trp Lys Lys
85 90 95
Ala Leu Phe Asn Ser Phe Leu Arg Val Asp Ser Glu Ile Glu Ser Val
100 105 110
Ala Pro Glu Thr Val Gly Ser Thr Ser Val Val Ala Val Val Phe Pro
115 120 125
Ser His Ile Phe Val Ala Asn Cys Gly Asp Ser Arg Ala Val Leu Cys
130 135 140
Arg Gly Lys Thr Ala Leu Pro Leu Ser Val Asp His Lys Pro Asp Arg
145 150 155 160
Glu Asp Glu Ala Ala Arg Ile Glu Ala Ala Gly Gly Lys Val Ile Gln
165 170 175
Trp Asn Gly Ala Arg Val Phe Gly Val Leu Ala Met Ser Arg Ser Ile
180 185 190
Gly Asp Arg Tyr Leu Lys Pro Ser Ile Ile Pro Asp Pro Glu Val Thr
195 200 205
Ala Val Lys Arg Val Lys Glu Asp Asp Cys Leu Ile Leu Ala Ser Asp
210 215 220
Gly Val Trp Asp Val Met Thr Asp Glu Glu Ala Cys Glu Met Ala Arg
225 230 235 240
Lys Arg Ile Leu Leu Trp His Lys Lys Asn Ala Val Ala Gly Asp Ala
245 250 255
Ser Leu Leu Ala Asp Glu Arg Arg Lys Glu Gly Lys Asp Pro Ala Ala
260 265 270
Met Ser Ala Ala Glu Tyr Leu Ser Lys Leu Ala Ile Gln Arg Gly Ser
275 280 285
Lys Asp Asn Ile Ser Val Val Val Val Asp Leu Lys
290 295 300
<210> 13
<211> 243
<212> PRT
<213> Artificial sequence (Artificial Sequence)
<400> 13
Met Gly Val Gln Val Glu Thr Ile Ser Pro Gly Asp Gly Arg Thr Phe
1 5 10 15
Pro Lys Arg Gly Gln Thr Cys Val Val His Tyr Thr Gly Met Leu Glu
20 25 30
Asp Gly Lys Lys Phe Asp Ser Ser Arg Asp Arg Asn Lys Pro Phe Lys
35 40 45
Phe Met Leu Gly Lys Gln Glu Val Ile Arg Gly Trp Glu Glu Gly Val
50 55 60
Ala Gln Met Ser Val Gly Gln Arg Ala Lys Leu Thr Ile Ser Pro Asp
65 70 75 80
Tyr Ala Tyr Gly Ala Thr Gly His Pro Gly Ile Ile Pro Pro His Ala
85 90 95
Thr Leu Val Phe Asp Val Glu Leu Leu Lys Leu Glu Lys Arg Thr Ala
100 105 110
Asp Gly Ser Glu Phe Glu Ser Pro Lys Lys Lys Arg Lys Val Met Ala
115 120 125
Ser Asn Phe Thr Gln Phe Val Leu Val Asp Asn Gly Gly Thr Gly Asp
130 135 140
Val Thr Val Ala Pro Ser Asn Phe Ala Asn Gly Ile Ala Glu Trp Ile
145 150 155 160
Ser Ser Asn Ser Arg Ser Gln Ala Tyr Lys Val Thr Cys Ser Val Arg
165 170 175
Gln Ser Ser Ala Gln Asn Arg Lys Tyr Thr Ile Lys Val Glu Val Pro
180 185 190
Lys Gly Ala Trp Arg Ser Tyr Leu Asn Met Glu Leu Thr Ile Pro Ile
195 200 205
Phe Ala Thr Asn Ser Asp Cys Glu Leu Ile Val Lys Ala Met Gln Gly
210 215 220
Leu Leu Lys Asp Gly Asn Pro Ile Pro Ser Ala Ile Ala Ala Asn Ser
225 230 235 240
Gly Ile Tyr
<210> 14
<211> 93
<212> PRT
<213> Artificial sequence (Artificial Sequence)
<400> 14
Ile Leu Trp His Glu Met Trp His Glu Gly Leu Glu Glu Ala Ser Arg
1 5 10 15
Leu Tyr Phe Gly Glu Arg Asn Val Lys Gly Met Phe Glu Val Leu Glu
20 25 30
Pro Leu His Ala Met Met Glu Arg Gly Pro Gln Thr Leu Lys Glu Thr
35 40 45
Ser Phe Asn Gln Ala Tyr Gly Arg Asp Leu Met Glu Ala Gln Glu Trp
50 55 60
Cys Arg Lys Tyr Met Lys Ser Gly Asn Val Lys Asp Leu Thr Gln Ala
65 70 75 80
Trp Asp Leu Tyr Tyr His Val Phe Arg Arg Ile Ser Lys
85 90
<210> 15
<211> 73
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 15
ataattgaag acataccgac ctgtgactca tgaaacacgt ttgagagcta gaaatagcaa 60
gttcaaataa ggc 73
<210> 16
<211> 63
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 16
ataattgaag acgcaaaact gtgactcatg aaatacagga agaatgtgca ccgactcggt 60
gcc 63
<210> 17
<211> 73
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 17
ataattgaag acataccggc accatgcaaa gaagtccggt ttgagagcta gaaatagcaa 60
gttcaaataa ggc 73
<210> 18
<211> 60
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 18
ataattgaag acgcaaaatg caaagaagtg cgaggcatct ggctgcaccg actcggtgcc 60
<210> 19
<211> 73
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 19
ataattgaag acataccgcc ggttgttgca atcttacggt ttgagagcta gaaatagcaa 60
gttcaaataa ggc 73
<210> 20
<211> 62
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 20
ataattgaag acgcaaaagt tgttgcaatc tttcgtggat gctgatgcac cgactcggtg 60
cc 62
<210> 21
<211> 73
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 21
ataattgaag acataccgtc acagataaac ttctgcacgt ttgagagcta gaaatagcaa 60
gttcaaataa ggc 73
<210> 22
<211> 63
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 22
ataattgaag acgcaaaaca cagataaact tctgaactgg aggggccgca ccgactcggt 60
gcc 63
<210> 23
<211> 73
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 23
ataattgaag acataccgcc ttactcaatc tctgttccgt ttgagagcta gaaatagcaa 60
gttcaaataa ggc 73
<210> 24
<211> 67
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 24
ataattgaag acgcaaaatt actcaatctc tgttactggg agcacctttt cgcaccgact 60
cggtgcc 67
<210> 25
<211> 73
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 25
ataattgaag acataccgtc cattcagatc atatcctagt ttgagagcta gaaatagcaa 60
gttcaaataa ggc 73
<210> 26
<211> 66
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 26
ataattgaag acgcaaaaca ttcagatcat atcataagga atctcagaaa gcaccgactc 60
ggtgcc 66
<210> 27
<211> 73
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 27
ataattgaag acataccgag cacatcaagg acattctagt ttgagagcta gaaatagcaa 60
gttcaaataa ggc 73
<210> 28
<211> 55
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 28
ataattgaag acgcaaaaca aggacattgt aaggatgatg caccgactcg gtgcc 55
<210> 29
<211> 73
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 29
ataattgaag acataccgct acctctgtga tactcttcgt ttgagagcta gaaatagcaa 60
gttcaaataa ggc 73
<210> 30
<211> 62
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 30
ataattgaag acgcaaaaac ctctgtgata ctcctcaggt gcacctgcac cgactcggtg 60
cc 62
<210> 31
<211> 73
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 31
ataattgaag acataccggc attttcagga ggaagcgagt ttgagagcta gaaatagcaa 60
gttcaaataa ggc 73
<210> 32
<211> 64
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 32
ataattgaag acgcaaaaat tttcaggagg aagcgattgc ttcagacagc accgactcgg 60
tgcc 64
<210> 33
<211> 78
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 33
ataattgaag acataccgag cctgtgtcca tataaagggt tttagagcta gaaatagcaa 60
gttaaaataa ggctagtc 78
<210> 34
<211> 61
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 34
ataattgaag acgcaaaatg tgtccatata atggaggagt tggaagcacc gactcggtgc 60
c 61
<210> 35
<211> 73
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 35
ataattgaag acataccgac ctgtgactca tgaaacacgt ttgagagcta gaaatagcaa 60
gttcaaataa ggc 73
<210> 36
<211> 82
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 36
ataattgaag acgcaaaaac atgggtgatc ctcatgtctg tgactcatga aatacaggaa 60
gaatgtgcac cgactcggtg cc 82
<210> 37
<211> 73
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 37
ataattgaag acataccggc accatgcaaa gaagtccggt ttgagagcta gaaatagcaa 60
gttcaaataa ggc 73
<210> 38
<211> 79
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 38
ataattgaag acgcaaaaac atgggtgatc ctcatgttgc aaagaagtgc gaggcatctg 60
gctgcaccga ctcggtgcc 79
<210> 39
<211> 73
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 39
ataattgaag acataccgcc ggttgttgca atcttacggt ttgagagcta gaaatagcaa 60
gttcaaataa ggc 73
<210> 40
<211> 81
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 40
ataattgaag acgcaaaaac atgggtgatc ctcatgtgtt gttgcaatct ttcgtggatg 60
ctgatgcacc gactcggtgc c 81
<210> 41
<211> 73
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 41
ataattgaag acataccgtc acagataaac ttctgcacgt ttgagagcta gaaatagcaa 60
gttcaaataa ggc 73
<210> 42
<211> 82
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 42
ataattgaag acgcaaaaac atgggtgatc ctcatgtcac agataaactt ctgaactgga 60
ggggccgcac cgactcggtg cc 82
<210> 43
<211> 73
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 43
ataattgaag acataccgcc ttactcaatc tctgttccgt ttgagagcta gaaatagcaa 60
gttcaaataa ggc 73
<210> 44
<211> 86
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 44
ataattgaag acgcaaaaac atgggtgatc ctcatgttta ctcaatctct gttactggga 60
gcaccttttc gcaccgactc ggtgcc 86
<210> 45
<211> 73
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 45
ataattgaag acataccgtc cattcagatc atatcctagt ttgagagcta gaaatagcaa 60
gttcaaataa ggc 73
<210> 46
<211> 85
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 46
ataattgaag acgcaaaaac atgggtgatc ctcatgtcat tcagatcata tcataaggaa 60
tctcagaaag caccgactcg gtgcc 85
<210> 47
<211> 73
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 47
ataattgaag acataccgag cacatcaagg acattctagt ttgagagcta gaaatagcaa 60
gttcaaataa ggc 73
<210> 48
<211> 74
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 48
ataattgaag acgcaaaaac atgggtgatc ctcatgtcaa ggacattgta aggatgatgc 60
accgactcgg tgcc 74
<210> 49
<211> 73
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 49
ataattgaag acataccgct acctctgtga tactcttcgt ttgagagcta gaaatagcaa 60
gttcaaataa ggc 73
<210> 50
<211> 81
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 50
ataattgaag acgcaaaaac atgggtgatc ctcatgtacc tctgtgatac tcctcaggtg 60
cacctgcacc gactcggtgc c 81
<210> 51
<211> 73
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 51
ataattgaag acataccggc attttcagga ggaagcgagt ttgagagcta gaaatagcaa 60
gttcaaataa ggc 73
<210> 52
<211> 83
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 52
ataattgaag acgcaaaaac atgggtgatc ctcatgtatt ttcaggagga agcgattgct 60
tcagacagca ccgactcggt gcc 83
<210> 53
<211> 78
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 53
ataattgaag acataccgag cctgtgtcca tataaagggt tttagagcta gaaatagcaa 60
gttaaaataa ggctagtc 78
<210> 54
<211> 80
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 54
ataattgaag acgcaaaaac atgggtgatc ctcatgttgt gtccatataa tggaggagtt 60
ggaagcaccg actcggtgcc 80
<210> 55
<211> 73
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 55
ataattgaag acataccggc attttcagga ggaagcgagt ttgagagcta gaaatagcaa 60
gttcaaataa ggc 73
<210> 56
<211> 83
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 56
ataattgaag acgcaaaaga tgctcgcagg cattcagatt ttcaggagga agcgattgct 60
tcagacagca ccgactcggt gcc 83
<210> 57
<211> 73
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 57
ataattgaag acataccggc attttcagga ggaagcgagt ttgagagcta gaaatagcaa 60
gttcaaataa ggc 73
<210> 58
<211> 89
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 58
ataattgaag acgcaaaagg agcgacgcca tatcgtctgc tccattttca ggaggaagcg 60
attgcttcag acagcaccga ctcggtgcc 89
<210> 59
<211> 73
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 59
ataattgaag acataccggc attttcagga ggaagcgagt ttgagagcta gaaatagcaa 60
gttcaaataa ggc 73
<210> 60
<211> 84
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 60
ataattgaag acgcaaaact gcctatacgg cagtgaacat tttcaggagg aagcgattgc 60
ttcagacagc accgactcgg tgcc 84
<210> 61
<211> 24
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 61
accgtggggt ttgatcgttt tctt 24
<210> 62
<211> 24
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 62
aaacaagaaa acgatcaaac ccca 24
<210> 63
<211> 23
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 63
accgatactt tagcagttcc agg 23
<210> 64
<211> 24
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 64
aaactcctgg aactgctaaa gtat 24
<210> 65
<211> 24
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 65
accgtgatta atttataaaa gttt 24
<210> 66
<211> 24
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 66
aaacaaactt ttataaatta atca 24
<210> 67
<211> 24
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 67
accgctgcac tcatcccagg cgtg 24
<210> 68
<211> 24
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 68
aaaccacgcc tgggatgagt gcag 24
<210> 69
<211> 24
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 69
accgccagta acagagattg agta 24
<210> 70
<211> 24
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 70
aaactactca atctctgtta ctgg 24
<210> 71
<211> 24
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 71
accgtcctta tgatatgatc tgaa 24
<210> 72
<211> 24
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 72
aaacttcaga tcatatcata agga 24
<210> 73
<211> 24
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 73
accgaagagt gaggagaagg cagg 24
<210> 74
<211> 24
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 74
aaaccctgcc ttctcctcac tctt 24
<210> 75
<211> 24
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 75
accggtcaat gctctccttt tcac 24
<210> 76
<211> 24
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 76
aaacgtgaaa aggagagcat tgac 24
<210> 77
<211> 24
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 77
accgcatgta ctcacctctc atga 24
<210> 78
<211> 24
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 78
aaactcatga gaggtgagta catg 24
<210> 79
<211> 40
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 79
ctacacgacg ctcttccgat ctgtggcggc atgattttgt 40
<210> 80
<211> 39
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 80
agacgtgtgc tcttccgatc tccaagcatt ttagataag 39
<210> 81
<211> 47
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 81
ctacacgacg ctcttccgat cttcatgccc agcaagtgct gtgaaac 47
<210> 82
<211> 46
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 82
agacgtgtgc tcttccgatc tgacactcac cgagcacatc ctagcc 46
<210> 83
<211> 57
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 83
ctacacgacg ctcttccgat ctagttggag agagtatgtt ttctatactt gagatga 57
<210> 84
<211> 53
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 84
agacgtgtgc tcttccgatc taactagata caggattctc ttgggtgata gtg 53
<210> 85
<211> 65
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 85
ctacacgacg ctcttccgat cttattttaa tggaattgaa atgtgatatc ctgtggttta 60
tgatg 65
<210> 86
<211> 58
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 86
agacgtgtgc tcttccgatc tccttcagta cttaaaaagt aagggcaatt tccagaaa 58
<210> 87
<211> 49
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 87
ctacacgacg ctcttccgat cttgcctcgc ttgttttcct tttgcagat 49
<210> 88
<211> 41
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 88
agacgtgtgc tcttccgatc tgcccttctg aggaggtgcc g 41
<210> 89
<211> 59
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 89
ctacacgacg ctcttccgat ctgaaatttt acggtttatt agccataatc atcttgcaa 59
<210> 90
<211> 61
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 90
agacgtgtgc tcttccgatc tgatgactta cactgaaaac ttgtagctaa taactactac 60
g 61
<210> 91
<211> 55
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 91
ctacacgacg ctcttccgat ctcttgtcac acacaatgaa actttgctgt tcact 55
<210> 92
<211> 62
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 92
agacgtgtgc tcttccgatc tagtagctaa catttttcag tacttaacta tatgccagct 60
at 62
<210> 93
<211> 61
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 93
ctacacgacg ctcttccgat ctaagcatta aatcttaaga ctacaagaca ttacttgaag 60
g 61
<210> 94
<211> 49
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 94
agacgtgtgc tcttccgatc tgacagagaa gggtgtaaaa gcttctagc 49
<210> 95
<211> 48
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 95
ctacacgacg ctcttccgat cttggttttc gctccgaagg taaaagaa 48
<210> 96
<211> 55
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 96
agacgtgtgc tcttccgatc tatatgcctc agtttgaatt cctctcacaa acaag 55
<210> 97
<211> 47
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 97
ctacacgacg ctcttccgat cttactgggg aaagcagtgc aggagca 47
<210> 98
<211> 42
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 98
agacgtgtgc tcttccgatc taccaccgct tcacagctgt gc 42
<210> 99
<211> 280
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 99
gtggcggcat gattttgtgc acggatggat aaaagtacct gtgactcatg aaacacagga 60
agaatgtctt gggatggcag tgttagatat gatgagaata gccaaagaaa acgatcaaac 120
cccactggcc atctataact ctatcaggta attttctttt gcaaatcctt acacataagt 180
gtgagtagag attttatata attcgtatat attttctgtg tttacccatg ccttttgatt 240
ttgtaatact agttaagtac tccttatcta aaatgcttgg 280
<210> 100
<211> 280
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 100
tcatgcccag caagtgctgt gaaacttaat aagcagcaga cggacatcgc tgtgaattgg 60
gctgggggcc tgcaccatgc aaagaagtcc gaggcatctg gcttctgtta cgtcaatgat 120
atcgtcttgg ccatcctgga actgctaaag tatgcctgcc tggccttgtc tcttggaaga 180
gcaccttagg ccaggttccc atttccctct tcccctgggc ttgcctccct agtttgcttt 240
tcctaccgat gtgctggcta ggatgtgctc ggtgagtgtc 280
<210> 101
<211> 280
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 101
agttggagag agtatgtttt ctatacttga gatgaaattt actgtatttt tattttcatt 60
aggttacctt gtatgaatgt cattcacaag gagaaatccg gttgttgcaa tcttacgtgg 120
atgctgatgt atcctttcct gggtttttaa tatctttagt caaaggaatt tattttcaat 180
aagtgcacca aaacttttat aaattaatca tttccctaaa gttattgttc tttcttaacc 240
gatttcttca ctatcaccca agagaatcct gtatctagtt 280
<210> 102
<211> 280
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 102
tattttaatg gaattgaaat gtgatatcct gtggtttatg atgcacgttg tttgtagctg 60
tagtgcttga ttttgggttt ctttcacaga taaacttctg cactggaggg gcctctcctc 120
ccctcgttct gcacatggag ctctaatccc cacgcctggg atgagtgcag aatatgcccc 180
gcagggtatt tgtaagttga gccttatttc ttctacaaat gtccatgtgt atagagatga 240
gaatttctgg aaattgccct tactttttaa gtactgaagg 280
<210> 103
<211> 280
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 103
tgcctcgctt gttttccttt tgcagatatt tttcccactt ttatatcatc tcagtgctgt 60
ggaatggctt cctgctttgg tgccttactc aatctctgtt cctgggagca ccttttccaa 120
gctggcttca tggtttgctc agaattctcg gggcggcaca gttccagggt aaggactccc 180
tgggcttatg acaacgctgc atcccgtttc tgttgttcct gtctgcaagg gagcagtttt 240
tggcattttg tctcctctct cggcacctcc tcagaagggc 280
<210> 104
<211> 280
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 104
gaaattttac ggtttattag ccataatcat cttgcaattt ttttccttta ggttttggct 60
tgtggttaac gggcatgttg ataaacatcc attcagatca tatcctaagg aatctcagaa 120
aaccaggaga tactggatac aaaataccaa ggggtacgta cagaaagtga agaatttctg 180
tgaaagttgc ttgccatggt tcctggctat tttagtgttg ccagctctaa gaagtagtag 240
cgtagtagtt attagctaca agttttcagt gtaagtcatc 280
<210> 105
<211> 280
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 105
cttgtcacac acaatgaaac tttgctgttc actgtcagtt ataacttaca tgaggtgacc 60
catttccatt caagggtttt agaagcacat caaggacatt ctaaggatga ttgacttaca 120
caatgatctc tgaacatgcc tcctgccttc tcctcactct tgagtatttg cttaggggag 180
cagaaaaaat actggtagca ttactgtaac attttaattc tgctttattt aaaaaagaca 240
tagctggcat atagttaagt actgaaaaat gttagctact 280
<210> 106
<211> 280
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 106
aagcattaaa tcttaagact acaagacatt acttgaaggt caatgctctc cttttcacag 60
gctactcaaa aagagattga gaaacagaag gtgcacctga agagtatcac agaggtagga 120
gaggccttga aaacagtttt gggcaagaag gagacgttgg tggaagataa actcagtctt 180
ctgaatagta actggatagc tgtcacctcc cgagcagaag agtggttaaa tcttttgttg 240
gtaagagaaa aggctagaag cttttacacc cttctctgtc 280
<210> 107
<211> 280
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 107
tggttttcgc tccgaaggta aaagaaatca ttgagtcccc cgccttcaga agagggtgca 60
ttttcaggag gaagcgatgg cttcagacag catatttgag tcatttcctt cgtacccaca 120
gtgcttcatg agaggtgagt acatgctggt cttgtaatat ctacttttgc tcagctttgc 180
ctgtaatgaa atggcagctt gtttcacctc ggtgcagaga tgcctcggtg cctgccagtt 240
ccctgtcttg tttgtgagag gaattcaaac tgaggcatat 280
<210> 108
<211> 280
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 108
tactggggaa agcagtgcag gagcagcggg gcccctgtgt ttcattcatg gctgggcttt 60
gtgactgtgg gcagcgagct cacctattct gagcctgtgt ccatataaag gaggagttgg 120
aagcggagaa ggttgatgtc catgagggag attggattct ggggtgaaga aagtgaggga 180
aagagcaggc aggtctgggc gcaaagcaca ggtgactgcc tgccaccagc ttgtgacccc 240
catcaagtta ctttgacttg cacagctgtg aagcggtggt 280
<210> 109
<211> 4757
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 109
acggatcggg agatctaccg gtacgcgttg acgtgtcttc ggatccggct tactaaaagc 60
cagataacag tatgcgtatt tgcgcgctga tttttgcggt ataagaatat atactgatat 120
gtatacccga agtatgtcaa aaagaggtat gctatgaagc agcgtattac agtgacagtt 180
gacagcgaca gctatcagtt gctcaaggca tatatgatgt caatatctcc ggtctggtaa 240
gcacaaccat gcagaatgaa gcccgtcgtc tgcgtgccga acgctggaaa gcggaaaatc 300
aggaagggat ggctgaggtc gcccggttta ttgaaatgaa cggctctttt gctgacgaga 360
acaggggctg gtgaaatgca gtttaaggtt tacacctata aaagagagag ccgttatcgt 420
ctgtttgtgg atgtacagag tgatattatt gacacgcccg ggcgacggat ggtgatcccc 480
ctggccagtg cacgtctgct gtcagataaa gtctcccgtg aactttaccc ggtggtgcat 540
atcggggatg aaagctggcg catgatgacc accgatatgg ccagtgtgcc ggtctccgtt 600
atcggggaag aagtggctga tctcagccac cgcgaaaatg acatcaaaaa cgccattaac 660
ctgatgttct ggggaatata aatgtcaggc tcccttatac acagccagtc tgcaggtcga 720
cgaagaccca ctcgcggccg cttggggttg cgccttttcc aaggcagccc tgggtttgcg 780
cagggacgcg gctgctctgg gcgtggttcc gggaaacgca gcggcgccga ccctgggtct 840
cgcacattct tcacgtccgt tcgcagcgtc acccggatct tcgccgctac ccttgtgggc 900
cccccggcga cgcttcctgc tccgccccta agtcgggaag gttccttgcg gttcgcggcg 960
tgccggacgt gacaaacgga agccgcacgt ctcactagta ccctcgcaga cggacagcgc 1020
cagggagcaa tggcagcgcg ccgaccgcga tgggctgtgg ccaatagcgg ctgctcagca 1080
gggcgcgccg agagcagcgg ccgggaaggg gcggtgcggg aggcggggtg tggggcggta 1140
gtgtgggccc tgttcctgcc cgcgcggtgt tccgcattct gcaagcctcc ggagcgcacg 1200
tcggcagtcg gctccctcgt tgaccgaatc accgacctct ctccccaggg ggatccgcca 1260
ccatgaccga gtacaagccc acggtgcgcc tcgccacccg cgacgacgtc cccagggccg 1320
tacgcaccct cgccgccgcg ttcgccgact accccgccac gcgccacacc gtcgatccgg 1380
accgccacat cgagcgggtc accgagctgc aagaactctt cctcacgcgc gtcgggctcg 1440
acatcggcaa ggtgtgggtc gcggacgacg gcgccgcggt ggcggtctgg accacgccgg 1500
agagcgtcga agcgggggcg gtgttcgccg agatcggccc gcgcatggcc gagttgagcg 1560
gttcccggct ggccgcgcag caacagatgg aaggcctcct ggcgccgcac cggcccaagg 1620
agcccgcgtg gttcctggcc accgtcggcg tctcgcccga ccaccagggc aagggtctgg 1680
gcagcgccgt cgtgctcccc ggagtggagg cggccgagcg cgccggggtg cccgccttcc 1740
tggagacctc cgcgccccgc aacctcccct tctacgagcg gctcggcttc accgtcaccg 1800
ccgacgtcga ggtgcccgaa ggaccgcgca cctggtgcat gacccgcaag cccggtgccg 1860
ctagcggtgc tactaacttc agcctgctga agcaggctgg agacgtggag gagaaccctg 1920
gacctggtag tggaacgcgt atggtgtcta agggcgaaga gctgattaag gagaacatgc 1980
acatgaagct gtacatggag ggcaccgtgg acaaccatca cttcaagtgc acatccgagg 2040
gcgaaggcaa gccctacgag ggcacccaga ccatgagaat caaggtggtc gagggcggcc 2100
ctctcccctt cgccttcgac atcctggcta ctagcttcct ctacggcagc aagaccttca 2160
tcaaccacac ccagggcatc cccgacttct tcaagcagtc cttccctgag ggcttcacat 2220
gggagagagt caccacatac gaagatgggg gcgtgctgac cgctacccag gacaccagcc 2280
tccaggacgg ctgcctcatc tacaacgtca agatcagagg ggtgaacttc acatccaacg 2340
gccctgtgat gcagaagaaa acactcggct gggaggcctt caccgagacg ctgtaccccg 2400
ctgacggcgg cctggaaggc agaaacgaca tggccctgaa gctcgtgggc gggagccatc 2460
tgatcgcaaa cgccaagacc acatatagat ccaagaaacc cgctaagaac ctcaagatgc 2520
ctggcatcta ctatgtggac tacagactgg aaagaatcaa ggaggccaac aacgaaacct 2580
acgtcgagca gcacgaggtg gcagtggcca gatactgcga cctccctagc aaactggggc 2640
acaagcttaa tccaaagaaa aagcggaaag tgtgagtcga cctcgagggg gggcccggta 2700
cctttaagac caatgactta caaggcagct gtagatctta gccacatgtc atcttattat 2760
tcagtattta taacttgcaa agaaatgaat atcagagagt gagaggaact tgtttattgc 2820
agcttataat ggttacaaat aaagcaatag catcacaaat ttcacaaata aagcattttt 2880
ttcactgcat tctagttgtg gtttgtccaa actcatcaat gtatcttatc atgtctggaa 2940
ttcacatgtg agcaaaaggc cagcaaaagg ccaggaaccg taaaaaggcc gcgttgctgg 3000
cgtttttcca taggctccgc ccccctgacg agcatcacaa aaatcgacgc tcaagtcaga 3060
ggtggcgaaa cccgacagga ctataaagat accaggcgtt tccccctgga agctccctcg 3120
tgcgctctcc tgttccgacc ctgccgctta ccggatacct gtccgccttt ctcccttcgg 3180
gaagcgtggc gctttctcat agctcacgct gtaggtatct cagttcggtg taggtcgttc 3240
gctccaagct gggctgtgtg cacgaacccc ccgttcagcc cgaccgctgc gccttatccg 3300
gtaactatcg tcttgagtcc aacccggtaa gacacgactt atcgccactg gcagcagcca 3360
ctggtaacag gattagcaga gcgaggtatg taggcggtgc tacagagttc ttgaagtggt 3420
ggcctaacta cggctacact agaagaacag tatttggtat ctgcgctctg ctgaagccag 3480
ttaccttcgg aaaaagagtt ggtagctctt gatccggcaa acaaaccacc gctggtagcg 3540
gtttttttgt ttgcaagcag cagattacgc gcagaaaaaa aggatctcaa gaagatcctt 3600
tgatcttttc tacggggtct gacgctcagt ggaacgaaaa ctcacgttaa gggattttgg 3660
tcatgagatt atcaaaaagg atcttcacct agatcctttt aaattaaaaa tgaagtttta 3720
aatcaatcta aagtatatat gagtaaactt ggtctgacag ttaccaatgc ttaatcagtg 3780
aggcacctat ctcagcgatc tgtctatttc gttcatccat agttgcctga ctccccgtcg 3840
tgtagataac tacgatacgg gagggcttac catctggccc cagtgctgca atgataccgc 3900
gagaaccacg ctcaccggct ccagatttat cagcaataaa ccagccagcc ggaagggccg 3960
agcgcagaag tggtcctgca actttatccg cctccatcca gtctattaat tgttgccggg 4020
aagctagagt aagtagttcg ccagttaata gtttgcgcaa cgttgttgcc attgctacag 4080
gcatcgtggt gtcacgctcg tcgtttggta tggcttcatt cagctccggt tcccaacgat 4140
caaggcgagt tacatgatcc cccatgttgt gcaaaaaagc ggttagctcc ttcggtcctc 4200
cgatcgttgt cagaagtaag ttggccgcag tgttatcact catggttatg gcagcactgc 4260
ataattctct tactgtcatg ccatccgtaa gatgcttttc tgtgactggt gagtactcaa 4320
ccaagtcatt ctgagaatag tgtatgcggc gaccgagttg ctcttgcccg gcgtcaatac 4380
gggataatac cgcgccacat agcagaactt taaaagtgct catcattgga aaacgttctt 4440
cggggcgaaa actctcaagg atcttaccgc tgttgagatc cagttcgatg taacccactc 4500
gtgcacccaa ctgatcttca gcatctttta ctttcaccag cgtttctggg tgagcaaaaa 4560
caggaaggca aaatgccgca aaaaagggaa taagggcgac acggaaatgt tgaatactca 4620
tactcttcct ttttcaatat tattgaagca tttatcaggg ttattgtctc atgagcggat 4680
acatatttga atgtatttag aaaaataaac aaataggggt tccgcgcaca tttccccgaa 4740
aagtgccacc tgacgtc 4757
<210> 110
<211> 8191
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 110
ttggggttgc gccttttcca aggcagccct gggtttgcgc agggacgcgg ctgctctggg 60
cgtggttccg ggaaacgcag cggcgccgac cctgggtctc gcacattctt cacgtccgtt 120
cgcagcgtca cccggatctt cgccgctacc cttgtgggcc ccccggcgac gcttcctgct 180
ccgcccctaa gtcgggaagg ttccttgcgg ttcgcggcgt gccggacgtg acaaacggaa 240
gccgcacgtc tcactagtac cctcgcagac ggacagcgcc agggagcaat ggcagcgcgc 300
cgaccgcgat gggctgtggc caatagcggc tgctcagcag ggcgcgccga gagcagcggc 360
cgggaagggg cggtgcggga ggcggggtgt ggggcggtag tgtgggccct gttcctgccc 420
gcgcggtgtt ccgcattctg caagcctccg gagcgcacgt cggcagtcgg ctccctcgtt 480
gaccgaatca ccgacctctc tccccagggg gatccaccgg atcaagcttg ccagctgggg 540
cgccctctgg taaggttggg aagccctgca gatctgatcc cggggggcaa tgagatatga 600
aaaagcctga actcaccgcg acgtctgtcg agaagtttct gatcgaaaag ttcgacagcg 660
tctccgacct gatgcagctc tcggagggcg aagaatctcg tgctttcagc ttcgatgtag 720
gagggcgtgg atatgtcctg cgggtaaata gctgcgccga tggtttctac aaagatcgtt 780
atgtttatcg gcactttgca tcggccgcgc tcccgattcc ggaagtgctt gacattgggg 840
aatttagcga gagcctgacc tattgcatct cccgccgtgc acagggtgtc acgttgcaag 900
atctgcctga aaccgaactg cccgctgttc tgcagccggt cgcggaggcc atggatgcga 960
tcgctgcggc cgatcttagc cagacgagcg ggttcggccc attcggaccg caaggaatcg 1020
gtcaatacac tacatggcgt gatttcatat gcgcgattgc tgatccccat gtgtatcact 1080
ggcaaactgt gatggacgac accgtcagtg cgtccgtcgc gcaggctctc gatgagctga 1140
tgctttgggc cgaggactgc cccgaagtcc ggcacctcgt gcacgcggat ttcggctcca 1200
acaatgtcct gacggacaat ggccgcataa cagcggtcat tgactggagc gaggcgatgt 1260
tcggggattc ccaatacgag gtcgccaaca tcttcttctg gaggccgtgg ttggcttgta 1320
tggagcagca gacgcgctac ttcgagcgga ggcatccgga gcttgcagga tcgccgcggc 1380
tccgggcgta tatgctccgc attggtcttg accaactcta tcagagcttg gttgacggca 1440
atttcgatga tgcagcttgg gcgcagggtc gatgcgacgc aatcgtccga tccggagccg 1500
ggactgtcgg gcgtacacaa atcgcccgca gaagcgcggc cgtctggacc gatggctgtg 1560
tagaagtact cgccgatagt ggaaaccgac gccccagcac tcgtccgagg gcaaaggaat 1620
agagtagatg ccgaccggga tctatcgata ccgtcgacct cgaggggggg cccggtacct 1680
ttaagaccaa tgacttacaa ggcagctgta gatcttagcc actttttaaa agaaaagggg 1740
ggactggaag ggctaattca ctcccaacga agaaaagatc tgctttttgc ttgtactggg 1800
tctctctggt tagaccagat ctgagcctgg gagctctctg gctaactagg gaacccactg 1860
cttaagcctc aataaagctt gccttgagtg cttcaagtag tgtgtgcccg tctgttgtgt 1920
gactctggta actagagatc cctcagaccc ttttagtcag tgtggaaaat ctctagcagt 1980
agtagttcat gtcatcttat tattcagtat ttataacttg caaagaaatg aatatcagag 2040
agtgagagga acttgtttat tgcagcttat aatggttaca aataaagcaa tagcatcaca 2100
aatttcacaa ataaagcatt tttttcactg cattctagtt gtggtttgtc caaactcatc 2160
aatgtatctt atcatgtctg gctctagcta tcccgcccct aactccgccc atcccgcccc 2220
taactccgcc cagttccgcc cattctccgc cccatggctg actaattttt tttatttatg 2280
cagaggccga ggccgcctcg gcctctgagc tattccagaa gtagtgagga ggcttttttg 2340
gaggcctagg gacgtaccca attcgcccta tagtgagtcg tattacgcgc gctcactggc 2400
cgtcgtttta caacgtcgtg actgggaaaa ccctggcgtt acccaactta atcgccttgc 2460
agcacatccc cctttcgcca gctggcgtaa tagcgaagag gcccgcaccg atcgcccttc 2520
ccaacagttg cgcagcctga atggcgaatg ggacgcgccc tgtagcggcg cattaagcgc 2580
ggcgggtgtg gtggttacgc gcagcgtgac cgctacactt gccagcgccc tagcgcccgc 2640
tcctttcgct ttcttccctt cctttctcgc cacgttcgcc ggctttcccc gtcaagctct 2700
aaatcggggg ctccctttag ggttccgatt tagtgcttta cggcacctcg accccaaaaa 2760
acttgattag ggtgatggtt cacgtagtgg gccatcgccc tgatagacgg tttttcgccc 2820
tttgacgttg gagtccacgt tctttaatag tggactcttg ttccaaactg gaacaacact 2880
caaccctatc tcggtctatt cttttgattt ataagggatt ttgccgattt cggcctattg 2940
gttaaaaaat gagctgattt aacaaaaatt taacgcgaat tttaacaaaa tattaacgct 3000
tacaatttag gtggcacttt tcggggaaat gtgcgcggaa cccctatttg tttatttttc 3060
taaatacatt caaatatgta tccgctcatg agacaataac cctgataaat gcttcaataa 3120
tattgaaaaa ggaagagtat gagtattcaa catttccgtg tcgcccttat tccctttttt 3180
gcggcatttt gccttcctgt ttttgctcac ccagaaacgc tggtgaaagt aaaagatgct 3240
gaagatcagt tgggtgcacg agtgggttac atcgaactgg atctcaacag cggtaagatc 3300
cttgagagtt ttcgccccga agaacgtttt ccaatgatga gcacttttaa agttctgcta 3360
tgtggcgcgg tattatcccg tattgacgcc gggcaagagc aactcggtcg ccgcatacac 3420
tattctcaga atgacttggt tgagtactca ccagtcacag aaaagcatct tacggatggc 3480
atgacagtaa gagaattatg cagtgctgcc ataaccatga gtgataacac tgcggccaac 3540
ttacttctga caacgatcgg aggaccgaag gagctaaccg cttttttgca caacatgggg 3600
gatcatgtaa ctcgccttga tcgttgggaa ccggagctga atgaagccat accaaacgac 3660
gagcgtgaca ccacgatgcc tgtagcaatg gcaacaacgt tgcgcaaact attaactggc 3720
gaactactta ctctagcttc ccggcaacaa ttaatagact ggatggaggc ggataaagtt 3780
gcaggaccac ttctgcgctc ggcccttccg gctggctggt ttattgctga taaatctgga 3840
gccggtgagc gtgggtctcg cggtatcatt gcagcactgg ggccagatgg taagccctcc 3900
cgtatcgtag ttatctacac gacggggagt caggcaacta tggatgaacg aaatagacag 3960
atcgctgaga taggtgcctc actgattaag cattggtaac tgtcagacca agtttactca 4020
tatatacttt agattgattt aaaacttcat ttttaattta aaaggatcta ggtgaagatc 4080
ctttttgata atctcatgac caaaatccct taacgtgagt tttcgttcca ctgagcgtca 4140
gaccccgtag aaaagatcaa aggatcttct tgagatcctt tttttctgcg cgtaatctgc 4200
tgcttgcaaa caaaaaaacc accgctacca gcggtggttt gtttgccgga tcaagagcta 4260
ccaactcttt ttccgaaggt aactggcttc agcagagcgc agataccaaa tactgttctt 4320
ctagtgtagc cgtagttagg ccaccacttc aagaactctg tagcaccgcc tacatacctc 4380
gctctgctaa tcctgttacc agtggctgct gccagtggcg ataagtcgtg tcttaccggg 4440
ttggactcaa gacgatagtt accggataag gcgcagcggt cgggctgaac ggggggttcg 4500
tgcacacagc ccagcttgga gcgaacgacc tacaccgaac tgagatacct acagcgtgag 4560
ctatgagaaa gcgccacgct tcccgaaggg agaaaggcgg acaggtatcc ggtaagcggc 4620
agggtcggaa caggagagcg cacgagggag cttccagggg gaaacgcctg gtatctttat 4680
agtcctgtcg ggtttcgcca cctctgactt gagcgtcgat ttttgtgatg ctcgtcaggg 4740
gggcggagcc tatggaaaaa cgccagcaac gcggcctttt tacggttcct ggccttttgc 4800
tggccttttg ctcacatgtt ctttcctgcg ttatcccctg attctgtgga taaccgtatt 4860
accgcctttg agtgagctga taccgctcgc cgcagccgaa cgaccgagcg cagcgagtca 4920
gtgagcgagg aagcggaaga gcgcccaata cgcaaaccgc ctctccccgc gcgttggccg 4980
attcattaat gcagctggca cgacaggttt cccgactgga aagcgggcag tgagcgcaac 5040
gcaattaatg tgagttagct cactcattag gcaccccagg ctttacactt tatgcttccg 5100
gctcgtatgt tgtgtggaat tgtgagcgga taacaatttc acacaggaaa cagctatgac 5160
catgattacg ccaagcgcgc aattaaccct cactaaaggg aacaaaagct ggagctgcaa 5220
gcttaatgta gtcttatgca atactcttgt agtcttgcaa catggtaacg atgagttagc 5280
aacatgcctt acaaggagag aaaaagcacc gtgcatgccg attggtggaa gtaaggtggt 5340
acgatcgtgc cttattagga aggcaacaga cgggtctgac atggattgga cgaaccactg 5400
aattgccgca ttgcagagat attgtattta agtgcctagc tcgatacata aacgggtctc 5460
tctggttaga ccagatctga gcctgggagc tctctggcta actagggaac ccactgctta 5520
agcctcaata aagcttgcct tgagtgcttc aagtagtgtg tgcccgtctg ttgtgtgact 5580
ctggtaacta gagatccctc agaccctttt agtcagtgtg gaaaatctct agcagtggcg 5640
cccgaacagg gacttgaaag cgaaagggaa accagaggag ctctctcgac gcaggactcg 5700
gcttgctgaa gcgcgcacgg caagaggcga ggggcggcga ctggtgagta cgccaaaaat 5760
tttgactagc ggaggctaga aggagagaga tgggtgcgag agcgtcagta ttaagcgggg 5820
gagaattaga tcgcgatggg aaaaaattcg gttaaggcca gggggaaaga aaaaatataa 5880
attaaaacat atagtatggg caagcaggga gctagaacga ttcgcagtta atcctggcct 5940
gttagaaaca tcagaaggct gtagacaaat actgggacag ctacaaccat cccttcagac 6000
aggatcagaa gaacttagat cattatataa tacagtagca accctctatt gtgtgcatca 6060
aaggatagag ataaaagaca ccaaggaagc tttagacaag atagaggaag agcaaaacaa 6120
aagtaagacc accgcacagc aagcggccgc tgatcttcag acctggagga ggagatatga 6180
gggacaattg gagaagtgaa ttatataaat ataaagtagt aaaaattgaa ccattaggag 6240
tagcacccac caaggcaaag agaagagtgg tgcagagaga aaaaagagca gtgggaatag 6300
gagctttgtt ccttgggttc ttgggagcag caggaagcac tatgggcgca gcgtcaatga 6360
cgctgacggt acaggccaga caattattgt ctggtatagt gcagcagcag aacaatttgc 6420
tgagggctat tgaggcgcaa cagcatctgt tgcaactcac agtctggggc atcaagcagc 6480
tccaggcaag aatcctggct gtggaaagat acctaaagga tcaacagctc ctggggattt 6540
ggggttgctc tggaaaactc atttgcacca ctgctgtgcc ttggaatgct agttggagta 6600
ataaatctct ggaacagatt tggaatcaca cgacctggat ggagtgggac agagaaatta 6660
acaattacac aagcttaata cactccttaa ttgaagaatc gcaaaaccag caagaaaaga 6720
atgaacaaga attattggaa ttagataaat gggcaagttt gtggaattgg tttaacataa 6780
caaattggct gtggtatata aaattattca taatgatagt aggaggcttg gtaggtttaa 6840
gaatagtttt tgctgtactt tctatagtga atagagttag gcagggatat tcaccattat 6900
cgtttcagac ccacctccca accccgaggg gacccgacag gcccgaagga atagaagaag 6960
aaggtggaga gagagacaga gacagatcca ttcgattagt gaacggatct cgacggtatc 7020
gatcacgaga ctagcctcga gcggccgccc ccttcaccga gggcctattt cccatgattc 7080
cttcatattt gcatatacga tacaaggctg ttagagagat aattggaatt aatttgactg 7140
taaacacaaa gatattagta caaaatacgt gacgtagaaa gtaataattt cttgggtagt 7200
ttgcagtttt aaaattatgt tttaaaatgg actatcatat gcttaccgta acttgaaagt 7260
atttcgattt cttggcttta tatatcttgt ggaaaggacg aaacaccggt gtcttcgagg 7320
cttactaaaa gccagataac agtatgcgta tttgcgcgct gatttttgcg gtataagaat 7380
atatactgat atgtataccc gaagtatgtc aaaaagaggt gtgctatgaa gcagcgtatt 7440
acagtgacag ttgacagcga cagctatcag ttgctcaagg catatatgat gtcaatatct 7500
ccggtctggt aagcacaacc atgcagaatg aagcccgtcg tctgcgtgcc gaacgctgga 7560
aagcggaaaa tcaggaaggg atggctgagg tcgcccggtt tattgaaatg aacggctctt 7620
ttgctgacga gaacagggac tggtgaaatg cagtttaagg tttacaccta taaaagagag 7680
agccgttatc gtctgtttgt ggatgtacag agtgatatta ttgacacgcc cgggcgacgg 7740
atggtgatcc ccctggccag tgcacgtctg ctgtcagata aagtctcccg tgaactttac 7800
ccggtggtgc atatcgggga tgaaagctgg cgcatgatga ccaccgatat ggccagtgtg 7860
ccggtctccg ttatcgggga agaagtggct gatctcagcc accgcgaaaa tgacatcaaa 7920
aacgccatta acctgatgtt ctggggaata taaaccctgc aggacgaaga cccttttttt 7980
gaattctcga cctcgagaca aatggcagta ttcatccaca attttaaaag aaaagggggg 8040
attggggggt acagtgcagg ggaaagaata gtagacataa tagcaacaga catacaaact 8100
aaagaattac aaaaacaaat tacaaaaatt caaaattttc gggtttatta cagggacagc 8160
agagatccac tttggccgcg gctcgagggg g 8191
<210> 111
<211> 8267
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 111
ttggggttgc gccttttcca aggcagccct gggtttgcgc agggacgcgg ctgctctggg 60
cgtggttccg ggaaacgcag cggcgccgac cctgggtctc gcacattctt cacgtccgtt 120
cgcagcgtca cccggatctt cgccgctacc cttgtgggcc ccccggcgac gcttcctgct 180
ccgcccctaa gtcgggaagg ttccttgcgg ttcgcggcgt gccggacgtg acaaacggaa 240
gccgcacgtc tcactagtac cctcgcagac ggacagcgcc agggagcaat ggcagcgcgc 300
cgaccgcgat gggctgtggc caatagcggc tgctcagcag ggcgcgccga gagcagcggc 360
cgggaagggg cggtgcggga ggcggggtgt ggggcggtag tgtgggccct gttcctgccc 420
gcgcggtgtt ccgcattctg caagcctccg gagcgcacgt cggcagtcgg ctccctcgtt 480
gaccgaatca ccgacctctc tccccagggg gatccaccgg atcaagcttg ccagctgggg 540
cgccctctgg taaggttggg aagccctgca gatctgatcc cggggggcaa tgagatatga 600
aaaagcctga actcaccgcg acgtctgtcg agaagtttct gatcgaaaag ttcgacagcg 660
tctccgacct gatgcagctc tcggagggcg aagaatctcg tgctttcagc ttcgatgtag 720
gagggcgtgg atatgtcctg cgggtaaata gctgcgccga tggtttctac aaagatcgtt 780
atgtttatcg gcactttgca tcggccgcgc tcccgattcc ggaagtgctt gacattgggg 840
aatttagcga gagcctgacc tattgcatct cccgccgtgc acagggtgtc acgttgcaag 900
atctgcctga aaccgaactg cccgctgttc tgcagccggt cgcggaggcc atggatgcga 960
tcgctgcggc cgatcttagc cagacgagcg ggttcggccc attcggaccg caaggaatcg 1020
gtcaatacac tacatggcgt gatttcatat gcgcgattgc tgatccccat gtgtatcact 1080
ggcaaactgt gatggacgac accgtcagtg cgtccgtcgc gcaggctctc gatgagctga 1140
tgctttgggc cgaggactgc cccgaagtcc ggcacctcgt gcacgcggat ttcggctcca 1200
acaatgtcct gacggacaat ggccgcataa cagcggtcat tgactggagc gaggcgatgt 1260
tcggggattc ccaatacgag gtcgccaaca tcttcttctg gaggccgtgg ttggcttgta 1320
tggagcagca gacgcgctac ttcgagcgga ggcatccgga gcttgcagga tcgccgcggc 1380
tccgggcgta tatgctccgc attggtcttg accaactcta tcagagcttg gttgacggca 1440
atttcgatga tgcagcttgg gcgcagggtc gatgcgacgc aatcgtccga tccggagccg 1500
ggactgtcgg gcgtacacaa atcgcccgca gaagcgcggc cgtctggacc gatggctgtg 1560
tagaagtact cgccgatagt ggaaaccgac gccccagcac tcgtccgagg gcaaaggaat 1620
agagtagatg ccgaccggga tctatcgata ccgtcgacct cgaggggggg cccggtacct 1680
ttaagaccaa tgacttacaa ggcagctgta gatcttagcc actttttaaa agaaaagggg 1740
ggactggaag ggctaattca ctcccaacga agaaaagatc tgctttttgc ttgtactggg 1800
tctctctggt tagaccagat ctgagcctgg gagctctctg gctaactagg gaacccactg 1860
cttaagcctc aataaagctt gccttgagtg cttcaagtag tgtgtgcccg tctgttgtgt 1920
gactctggta actagagatc cctcagaccc ttttagtcag tgtggaaaat ctctagcagt 1980
agtagttcat gtcatcttat tattcagtat ttataacttg caaagaaatg aatatcagag 2040
agtgagagga acttgtttat tgcagcttat aatggttaca aataaagcaa tagcatcaca 2100
aatttcacaa ataaagcatt tttttcactg cattctagtt gtggtttgtc caaactcatc 2160
aatgtatctt atcatgtctg gctctagcta tcccgcccct aactccgccc atcccgcccc 2220
taactccgcc cagttccgcc cattctccgc cccatggctg actaattttt tttatttatg 2280
cagaggccga ggccgcctcg gcctctgagc tattccagaa gtagtgagga ggcttttttg 2340
gaggcctagg gacgtaccca attcgcccta tagtgagtcg tattacgcgc gctcactggc 2400
cgtcgtttta caacgtcgtg actgggaaaa ccctggcgtt acccaactta atcgccttgc 2460
agcacatccc cctttcgcca gctggcgtaa tagcgaagag gcccgcaccg atcgcccttc 2520
ccaacagttg cgcagcctga atggcgaatg ggacgcgccc tgtagcggcg cattaagcgc 2580
ggcgggtgtg gtggttacgc gcagcgtgac cgctacactt gccagcgccc tagcgcccgc 2640
tcctttcgct ttcttccctt cctttctcgc cacgttcgcc ggctttcccc gtcaagctct 2700
aaatcggggg ctccctttag ggttccgatt tagtgcttta cggcacctcg accccaaaaa 2760
acttgattag ggtgatggtt cacgtagtgg gccatcgccc tgatagacgg tttttcgccc 2820
tttgacgttg gagtccacgt tctttaatag tggactcttg ttccaaactg gaacaacact 2880
caaccctatc tcggtctatt cttttgattt ataagggatt ttgccgattt cggcctattg 2940
gttaaaaaat gagctgattt aacaaaaatt taacgcgaat tttaacaaaa tattaacgct 3000
tacaatttag gtggcacttt tcggggaaat gtgcgcggaa cccctatttg tttatttttc 3060
taaatacatt caaatatgta tccgctcatg agacaataac cctgataaat gcttcaataa 3120
tattgaaaaa ggaagagtat gagtattcaa catttccgtg tcgcccttat tccctttttt 3180
gcggcatttt gccttcctgt ttttgctcac ccagaaacgc tggtgaaagt aaaagatgct 3240
gaagatcagt tgggtgcacg agtgggttac atcgaactgg atctcaacag cggtaagatc 3300
cttgagagtt ttcgccccga agaacgtttt ccaatgatga gcacttttaa agttctgcta 3360
tgtggcgcgg tattatcccg tattgacgcc gggcaagagc aactcggtcg ccgcatacac 3420
tattctcaga atgacttggt tgagtactca ccagtcacag aaaagcatct tacggatggc 3480
atgacagtaa gagaattatg cagtgctgcc ataaccatga gtgataacac tgcggccaac 3540
ttacttctga caacgatcgg aggaccgaag gagctaaccg cttttttgca caacatgggg 3600
gatcatgtaa ctcgccttga tcgttgggaa ccggagctga atgaagccat accaaacgac 3660
gagcgtgaca ccacgatgcc tgtagcaatg gcaacaacgt tgcgcaaact attaactggc 3720
gaactactta ctctagcttc ccggcaacaa ttaatagact ggatggaggc ggataaagtt 3780
gcaggaccac ttctgcgctc ggcccttccg gctggctggt ttattgctga taaatctgga 3840
gccggtgagc gtgggtctcg cggtatcatt gcagcactgg ggccagatgg taagccctcc 3900
cgtatcgtag ttatctacac gacggggagt caggcaacta tggatgaacg aaatagacag 3960
atcgctgaga taggtgcctc actgattaag cattggtaac tgtcagacca agtttactca 4020
tatatacttt agattgattt aaaacttcat ttttaattta aaaggatcta ggtgaagatc 4080
ctttttgata atctcatgac caaaatccct taacgtgagt tttcgttcca ctgagcgtca 4140
gaccccgtag aaaagatcaa aggatcttct tgagatcctt tttttctgcg cgtaatctgc 4200
tgcttgcaaa caaaaaaacc accgctacca gcggtggttt gtttgccgga tcaagagcta 4260
ccaactcttt ttccgaaggt aactggcttc agcagagcgc agataccaaa tactgttctt 4320
ctagtgtagc cgtagttagg ccaccacttc aagaactctg tagcaccgcc tacatacctc 4380
gctctgctaa tcctgttacc agtggctgct gccagtggcg ataagtcgtg tcttaccggg 4440
ttggactcaa gacgatagtt accggataag gcgcagcggt cgggctgaac ggggggttcg 4500
tgcacacagc ccagcttgga gcgaacgacc tacaccgaac tgagatacct acagcgtgag 4560
ctatgagaaa gcgccacgct tcccgaaggg agaaaggcgg acaggtatcc ggtaagcggc 4620
agggtcggaa caggagagcg cacgagggag cttccagggg gaaacgcctg gtatctttat 4680
agtcctgtcg ggtttcgcca cctctgactt gagcgtcgat ttttgtgatg ctcgtcaggg 4740
gggcggagcc tatggaaaaa cgccagcaac gcggcctttt tacggttcct ggccttttgc 4800
tggccttttg ctcacatgtt ctttcctgcg ttatcccctg attctgtgga taaccgtatt 4860
accgcctttg agtgagctga taccgctcgc cgcagccgaa cgaccgagcg cagcgagtca 4920
gtgagcgagg aagcggaaga gcgcccaata cgcaaaccgc ctctccccgc gcgttggccg 4980
attcattaat gcagctggca cgacaggttt cccgactgga aagcgggcag tgagcgcaac 5040
gcaattaatg tgagttagct cactcattag gcaccccagg ctttacactt tatgcttccg 5100
gctcgtatgt tgtgtggaat tgtgagcgga taacaatttc acacaggaaa cagctatgac 5160
catgattacg ccaagcgcgc aattaaccct cactaaaggg aacaaaagct ggagctgcaa 5220
gcttaatgta gtcttatgca atactcttgt agtcttgcaa catggtaacg atgagttagc 5280
aacatgcctt acaaggagag aaaaagcacc gtgcatgccg attggtggaa gtaaggtggt 5340
acgatcgtgc cttattagga aggcaacaga cgggtctgac atggattgga cgaaccactg 5400
aattgccgca ttgcagagat attgtattta agtgcctagc tcgatacata aacgggtctc 5460
tctggttaga ccagatctga gcctgggagc tctctggcta actagggaac ccactgctta 5520
agcctcaata aagcttgcct tgagtgcttc aagtagtgtg tgcccgtctg ttgtgtgact 5580
ctggtaacta gagatccctc agaccctttt agtcagtgtg gaaaatctct agcagtggcg 5640
cccgaacagg gacttgaaag cgaaagggaa accagaggag ctctctcgac gcaggactcg 5700
gcttgctgaa gcgcgcacgg caagaggcga ggggcggcga ctggtgagta cgccaaaaat 5760
tttgactagc ggaggctaga aggagagaga tgggtgcgag agcgtcagta ttaagcgggg 5820
gagaattaga tcgcgatggg aaaaaattcg gttaaggcca gggggaaaga aaaaatataa 5880
attaaaacat atagtatggg caagcaggga gctagaacga ttcgcagtta atcctggcct 5940
gttagaaaca tcagaaggct gtagacaaat actgggacag ctacaaccat cccttcagac 6000
aggatcagaa gaacttagat cattatataa tacagtagca accctctatt gtgtgcatca 6060
aaggatagag ataaaagaca ccaaggaagc tttagacaag atagaggaag agcaaaacaa 6120
aagtaagacc accgcacagc aagcggccgc tgatcttcag acctggagga ggagatatga 6180
gggacaattg gagaagtgaa ttatataaat ataaagtagt aaaaattgaa ccattaggag 6240
tagcacccac caaggcaaag agaagagtgg tgcagagaga aaaaagagca gtgggaatag 6300
gagctttgtt ccttgggttc ttgggagcag caggaagcac tatgggcgca gcgtcaatga 6360
cgctgacggt acaggccaga caattattgt ctggtatagt gcagcagcag aacaatttgc 6420
tgagggctat tgaggcgcaa cagcatctgt tgcaactcac agtctggggc atcaagcagc 6480
tccaggcaag aatcctggct gtggaaagat acctaaagga tcaacagctc ctggggattt 6540
ggggttgctc tggaaaactc atttgcacca ctgctgtgcc ttggaatgct agttggagta 6600
ataaatctct ggaacagatt tggaatcaca cgacctggat ggagtgggac agagaaatta 6660
acaattacac aagcttaata cactccttaa ttgaagaatc gcaaaaccag caagaaaaga 6720
atgaacaaga attattggaa ttagataaat gggcaagttt gtggaattgg tttaacataa 6780
caaattggct gtggtatata aaattattca taatgatagt aggaggcttg gtaggtttaa 6840
gaatagtttt tgctgtactt tctatagtga atagagttag gcagggatat tcaccattat 6900
cgtttcagac ccacctccca accccgaggg gacccgacag gcccgaagga atagaagaag 6960
aaggtggaga gagagacaga gacagatcca ttcgattagt gaacggatct cgacggtatc 7020
gatcacgaga ctagcctcga gcggccgccc ccttcaccga gggcctattt cccatgattc 7080
cttcatattt gcatatacga tacaaggctg ttagagagat aattggaatt aatttgactg 7140
taaacacaaa gatattagta caaaatacgt gacgtagaaa gtaataattt cttgggtagt 7200
ttgcagtttt aaaattatgt tttaaaatgg actatcatat gcttaccgta acttgaaagt 7260
atttcgattt cttggcttta tatatcttgt ggaaaggacg aaacaccggt gtcttcgagg 7320
cttactaaaa gccagataac agtatgcgta tttgcgcgct gatttttgcg gtataagaat 7380
atatactgat atgtataccc gaagtatgtc aaaaagaggt gtgctatgaa gcagcgtatt 7440
acagtgacag ttgacagcga cagctatcag ttgctcaagg catatatgat gtcaatatct 7500
ccggtctggt aagcacaacc atgcagaatg aagcccgtcg tctgcgtgcc gaacgctgga 7560
aagcggaaaa tcaggaaggg atggctgagg tcgcccggtt tattgaaatg aacggctctt 7620
ttgctgacga gaacagggac tggtgaaatg cagtttaagg tttacaccta taaaagagag 7680
agccgttatc gtctgtttgt ggatgtacag agtgatatta ttgacacgcc cgggcgacgg 7740
atggtgatcc ccctggccag tgcacgtctg ctgtcagata aagtctcccg tgaactttac 7800
ccggtggtgc atatcgggga tgaaagctgg cgcatgatga ccaccgatat ggccagtgtg 7860
ccggtctccg ttatcgggga agaagtggct gatctcagcc accgcgaaaa tgacatcaaa 7920
aacgccatta acctgatgtt ctggggaata taaaccctgc aggacgaaga cccgttttag 7980
agctagaaat agcaagttaa aataaggcta gtccgttatc aacttgaaaa agtggcaccg 8040
agtcggtgct ttttttgaat tctcgacctc gagacaaatg gcagtattca tccacaattt 8100
taaaagaaaa ggggggattg gggggtacag tgcaggggaa agaatagtag acataatagc 8160
aacagacata caaactaaag aattacaaaa acaaattaca aaaattcaaa attttcgggt 8220
ttattacagg gacagcagag atccactttg gccgcggctc gaggggg 8267
<210> 112
<211> 4472
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 112
acggatcggg agatctaccg gtacgcgttg acagagacgg gatccgacat tgattattga 60
ctagttatta atagtaatca attacggggt cattagttca tagcccatat atggagttcc 120
gcgttacata acttacggta aatggcccgc ctggctgacc gcccaacgac ccccgcccat 180
tgacgtcaat aatgacgtat gttcccatag taacgccaat agggactttc cattgacgtc 240
aatgggtgga gtatttacgg taaactgccc acttggcagt acatcaagtg tatcatatgc 300
caagtacgcc ccctattgac gtcaatgacg gtaaatggcc cgcctggcat tatgcccagt 360
acatgacctt atgggacttt cctacttggc agtacatcta cgtattagtc atcgctatta 420
ccatggtgat gcggttttgg cagtacatca atgggcgtgg atagcggttt gactcacggg 480
gatttccaag tctccacccc attgacgtca atgggagttt gttttggcac caaaatcaac 540
gggactttcc aaaatgtcgt aacaactccg ccccattgac gcaaatgggc ggtaggcgtg 600
tacggtggga ggtctatata agcagagctg gtttagtgaa ccgtcagatc cgctagagat 660
ccgcggccgc taatacgact cactataggg agagccgcca ccatgggagt gcaggtggaa 720
accatctccc caggagacgg gcgcaccttc cccaagcgcg gccagacctg cgtggtgcac 780
tacaccggga tgcttgaaga tggaaagaaa tttgattcct ctcgggacag aaacaagccc 840
tttaagttta tgctaggcaa gcaggaggtg atccgaggct gggaagaagg ggttgcccag 900
atgagtgtgg gtcagagagc caaactgact atatctccag attatgccta tggtgccact 960
gggcacccag gcatcatccc accacatgcc actctcgtct tcgatgtgga gcttctaaaa 1020
ctggaaaaac ggacagccga cggaagcgag ttcgagtcac caaagaagaa gcggaaagtc 1080
atggcttcta actttactca gttcgttctc gtcgacaatg gcggaactgg cgacgtgact 1140
gttgccccaa gcaacttcgc taacgggatc gctgaatgga tcagctctaa ctcgcgttca 1200
caggcttaca aagtaacctg tagcgttcgt cagagctctg cgcagaatcg caaatacacc 1260
atcaaagtcg aggtgcctaa aggcgcctgg cgttcgtact taaatatgga actaaccatt 1320
ccaattttcg ccacgaattc cgactgcgag cttattgtta aggcaatgca aggtctccta 1380
aaagatggaa acccgattcc ctcagcaatc gcagcaaact ccggcatcta cgagggcaga 1440
ggaagtcttc taacatgcgg tgacgtggag gagaatcccg gccctgctag cggtactagc 1500
atggcagaaa tcggtactgg ctttccattc gacccccatt atgtggaagt cctgggcgag 1560
cgcatgcact acgtcgatgt tggtccgcgc gatggcaccc ctgtgctgtt cctgcacggt 1620
aacccgacct cctcctacgt gtggcgcaac atcatcccgc atgttgcacc gacccatcgc 1680
tgcattgctc cagacctgat cggtatgggc aaatccgaca aaccagacct gggttatttc 1740
ttcgacgacc acgtccgctt catggatgcc ttcatcgaag ccctgggtct ggaagaggtc 1800
gtcctggtca ttcacgactg gggctccgct ctgggtttcc actgggccaa gcgcaatcca 1860
gagcgcgtca aaggtattgc atttatggag ttcatccgcc ctatcccgac ctgggacgaa 1920
tggccagaat ttgcccgcga gaccttccag gccttccgca ccaccgacgt cggccgcaag 1980
ctgatcatcg atcagaacgt ttttatcgag ggtacgctgc cgatgggtgt cgtccgcccg 2040
ctgactgaag tcgagatgga ccattaccgc gagccgttcc tgaatcctgt tgaccgcgag 2100
ccactgtggc gcttcccaaa cgagctgcca atcgccggtg agccagcgaa catcgtcgcg 2160
ctggtcgaag aatacatgga ctggctgcac cagtcccctg tcccgaagct gctgttctgg 2220
ggcaccccag gcgttctgat cccaccggcc gaagccgctc gcctggccaa aagcctgcct 2280
aactgcaagg ctgtggacat cggcccgggt ctgaatctgc tgcaagaaga caacccggac 2340
ctgatcggca gcgagatcgc gcgctggctg tcgacgctgg agatttccgg ctaagtttaa 2400
acccgctgat cagcctcgac tgtgccttct agttgccagc catctgttgt ttgcccctcc 2460
cccgtgcctt ccttgaccct ggaaggtgcc actcccactg tcctttccta ataaaatgag 2520
aaaattgcat cgcattgtct gagtaggtgt cattctattc tggggggtgg ggtggggcag 2580
gacagcaagg gggaggattg ggaagacaat agcaggcatg ctggggatgc ggtgggctct 2640
atgggcggcc gcgaattcac atgtgagcaa aaggccagca aaaggccagg aaccgtaaaa 2700
aggccgcgtt gctggcgttt ttccataggc tccgcccccc tgacgagcat cacaaaaatc 2760
gacgctcaag tcagaggtgg cgaaacccga caggactata aagataccag gcgtttcccc 2820
ctggaagctc cctcgtgcgc tctcctgttc cgaccctgcc gcttaccgga tacctgtccg 2880
cctttctccc ttcgggaagc gtggcgcttt ctcatagctc acgctgtagg tatctcagtt 2940
cggtgtaggt cgttcgctcc aagctgggct gtgtgcacga accccccgtt cagcccgacc 3000
gctgcgcctt atccggtaac tatcgtcttg agtccaaccc ggtaagacac gacttatcgc 3060
cactggcagc agccactggt aacaggatta gcagagcgag gtatgtaggc ggtgctacag 3120
agttcttgaa gtggtggcct aactacggct acactagaag aacagtattt ggtatctgcg 3180
ctctgctgaa gccagttacc ttcggaaaaa gagttggtag ctcttgatcc ggcaaacaaa 3240
ccaccgctgg tagcggtttt tttgtttgca agcagcagat tacgcgcaga aaaaaaggat 3300
ctcaagaaga tcctttgatc ttttctacgg ggtctgacgc tcagtggaac gaaaactcac 3360
gttaagggat tttggtcatg agattatcaa aaaggatctt cacctagatc cttttaaatt 3420
aaaaatgaag ttttaaatca atctaaagta tatatgagta aacttggtct gacagttacc 3480
aatgcttaat cagtgaggca cctatctcag cgatctgtct atttcgttca tccatagttg 3540
cctgactccc cgtcgtgtag ataactacga tacgggaggg cttaccatct ggccccagtg 3600
ctgcaatgat accgcgagaa ccacgctcac cggctccaga tttatcagca ataaaccagc 3660
cagccggaag ggccgagcgc agaagtggtc ctgcaacttt atccgcctcc atccagtcta 3720
ttaattgttg ccgggaagct agagtaagta gttcgccagt taatagtttg cgcaacgttg 3780
ttgccattgc tacaggcatc gtggtgtcac gctcgtcgtt tggtatggct tcattcagct 3840
ccggttccca acgatcaagg cgagttacat gatcccccat gttgtgcaaa aaagcggtta 3900
gctccttcgg tcctccgatc gttgtcagaa gtaagttggc cgcagtgtta tcactcatgg 3960
ttatggcagc actgcataat tctcttactg tcatgccatc cgtaagatgc ttttctgtga 4020
ctggtgagta ctcaaccaag tcattctgag aatagtgtat gcggcgaccg agttgctctt 4080
gcccggcgtc aatacgggat aataccgcgc cacatagcag aactttaaaa gtgctcatca 4140
ttggaaaacg ttcttcgggg cgaaaactct caaggatctt accgctgttg agatccagtt 4200
cgatgtaacc cactcgtgca cccaactgat cttcagcatc ttttactttc accagcgttt 4260
ctgggtgagc aaaaacagga aggcaaaatg ccgcaaaaaa gggaataagg gcgacacgga 4320
aatgttgaat actcatactc ttcctttttc aatattattg aagcatttat cagggttatt 4380
gtctcatgag cggatacata tttgaatgta tttagaaaaa taaacaaata ggggttccgc 4440
gcacatttcc ccgaaaagtg ccacctgacg tc 4472
<210> 113
<211> 4694
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 113
acggatcggg agatctaccg gtacgcgttg acagagacgg gatccgacat tgattattga 60
ctagttatta atagtaatca attacggggt cattagttca tagcccatat atggagttcc 120
gcgttacata acttacggta aatggcccgc ctggctgacc gcccaacgac ccccgcccat 180
tgacgtcaat aatgacgtat gttcccatag taacgccaat agggactttc cattgacgtc 240
aatgggtgga gtatttacgg taaactgccc acttggcagt acatcaagtg tatcatatgc 300
caagtacgcc ccctattgac gtcaatgacg gtaaatggcc cgcctggcat tatgcccagt 360
acatgacctt atgggacttt cctacttggc agtacatcta cgtattagtc atcgctatta 420
ccatggtgat gcggttttgg cagtacatca atgggcgtgg atagcggttt gactcacggg 480
gatttccaag tctccacccc attgacgtca atgggagttt gttttggcac caaaatcaac 540
gggactttcc aaaatgtcgt aacaactccg ccccattgac gcaaatgggc ggtaggcgtg 600
tacggtggga ggtctatata agcagagctg gtttagtgaa ccgtcagatc cgctagagat 660
ccgcggccgc taatacgact cactataggg agagccgcca ccggtggggg cgcgccaact 720
caagacgaat tcacccaact ctcccaatca atcgccgagt tccacacgta ccaactcggt 780
aacggccgtt gctcatctct cctagctcag cgaatccacg cgccgccgga aacagtatgg 840
tccgtggtga gacgtttcga taggccacag atttacaaac acttcatcaa aagctgtaac 900
gtgagtgaag atttcgagat gcgagtggga tgcacgcgcg acgtgaacgt gataagtgga 960
ttaccggcga atacgtctcg agagagatta gatctgttgg acgatgatcg gagagtgact 1020
gggtttagta taaccggtgg tgaacatagg ctgaggaatt ataaatcggt tacgacggtt 1080
catagatttg agaaagaaga agaagaagaa aggatctgga ccgttgtttt ggaatcttat 1140
gttgttgatg taccggaagg taattcggag gaagatacga gattgtttgc tgatacggtt 1200
attagattga atcttcagaa acttgcttcg atcactgaag ctatgaacaa acggacagcc 1260
gacggaagcg agttcgagtc accaaagaag aagcggaaag tcatggcttc taactttact 1320
cagttcgttc tcgtcgacaa tggcggaact ggcgacgtga ctgttgcccc aagcaacttc 1380
gctaacggga tcgctgaatg gatcagctct aactcgcgtt cacaggctta caaagtaacc 1440
tgtagcgttc gtcagagctc tgcgcagaat cgcaaataca ccatcaaagt cgaggtgcct 1500
aaaggcgcct ggcgttcgta cttaaatatg gaactaacca ttccaatttt cgccacgaat 1560
tccgactgcg agcttattgt taaggcaatg caaggtctcc taaaagatgg aaacccgatt 1620
ccctcagcaa tcgcagcaaa ctccggcatc tacgagggca gaggaagtct tctaacatgc 1680
ggtgacgtgg aggagaatcc cggccctgct agcggtacta gcatggcaga aatcggtact 1740
ggctttccat tcgaccccca ttatgtggaa gtcctgggcg agcgcatgca ctacgtcgat 1800
gttggtccgc gcgatggcac ccctgtgctg ttcctgcacg gtaacccgac ctcctcctac 1860
gtgtggcgca acatcatccc gcatgttgca ccgacccatc gctgcattgc tccagacctg 1920
atcggtatgg gcaaatccga caaaccagac ctgggttatt tcttcgacga ccacgtccgc 1980
ttcatggatg ccttcatcga agccctgggt ctggaagagg tcgtcctggt cattcacgac 2040
tggggctccg ctctgggttt ccactgggcc aagcgcaatc cagagcgcgt caaaggtatt 2100
gcatttatgg agttcatccg ccctatcccg acctgggacg aatggccaga atttgcccgc 2160
gagaccttcc aggccttccg caccaccgac gtcggccgca agctgatcat cgatcagaac 2220
gtttttatcg agggtacgct gccgatgggt gtcgtccgcc cgctgactga agtcgagatg 2280
gaccattacc gcgagccgtt cctgaatcct gttgaccgcg agccactgtg gcgcttccca 2340
aacgagctgc caatcgccgg tgagccagcg aacatcgtcg cgctggtcga agaatacatg 2400
gactggctgc accagtcccc tgtcccgaag ctgctgttct ggggcacccc aggcgttctg 2460
atcccaccgg ccgaagccgc tcgcctggcc aaaagcctgc ctaactgcaa ggctgtggac 2520
atcggcccgg gtctgaatct gctgcaagaa gacaacccgg acctgatcgg cagcgagatc 2580
gcgcgctggc tgtcgacgct ggagatttcc ggctaagttt aaacccgctg atcagcctcg 2640
actgtgcctt ctagttgcca gccatctgtt gtttgcccct cccccgtgcc ttccttgacc 2700
ctggaaggtg ccactcccac tgtcctttcc taataaaatg agaaaattgc atcgcattgt 2760
ctgagtaggt gtcattctat tctggggggt ggggtggggc aggacagcaa gggggaggat 2820
tgggaagaca atagcaggca tgctggggat gcggtgggct ctatgggcgg ccgcgaattc 2880
acatgtgagc aaaaggccag caaaaggcca ggaaccgtaa aaaggccgcg ttgctggcgt 2940
ttttccatag gctccgcccc cctgacgagc atcacaaaaa tcgacgctca agtcagaggt 3000
ggcgaaaccc gacaggacta taaagatacc aggcgtttcc ccctggaagc tccctcgtgc 3060
gctctcctgt tccgaccctg ccgcttaccg gatacctgtc cgcctttctc ccttcgggaa 3120
gcgtggcgct ttctcatagc tcacgctgta ggtatctcag ttcggtgtag gtcgttcgct 3180
ccaagctggg ctgtgtgcac gaaccccccg ttcagcccga ccgctgcgcc ttatccggta 3240
actatcgtct tgagtccaac ccggtaagac acgacttatc gccactggca gcagccactg 3300
gtaacaggat tagcagagcg aggtatgtag gcggtgctac agagttcttg aagtggtggc 3360
ctaactacgg ctacactaga agaacagtat ttggtatctg cgctctgctg aagccagtta 3420
ccttcggaaa aagagttggt agctcttgat ccggcaaaca aaccaccgct ggtagcggtt 3480
tttttgtttg caagcagcag attacgcgca gaaaaaaagg atctcaagaa gatcctttga 3540
tcttttctac ggggtctgac gctcagtgga acgaaaactc acgttaaggg attttggtca 3600
tgagattatc aaaaaggatc ttcacctaga tccttttaaa ttaaaaatga agttttaaat 3660
caatctaaag tatatatgag taaacttggt ctgacagtta ccaatgctta atcagtgagg 3720
cacctatctc agcgatctgt ctatttcgtt catccatagt tgcctgactc cccgtcgtgt 3780
agataactac gatacgggag ggcttaccat ctggccccag tgctgcaatg ataccgcgag 3840
aaccacgctc accggctcca gatttatcag caataaacca gccagccgga agggccgagc 3900
gcagaagtgg tcctgcaact ttatccgcct ccatccagtc tattaattgt tgccgggaag 3960
ctagagtaag tagttcgcca gttaatagtt tgcgcaacgt tgttgccatt gctacaggca 4020
tcgtggtgtc acgctcgtcg tttggtatgg cttcattcag ctccggttcc caacgatcaa 4080
ggcgagttac atgatccccc atgttgtgca aaaaagcggt tagctccttc ggtcctccga 4140
tcgttgtcag aagtaagttg gccgcagtgt tatcactcat ggttatggca gcactgcata 4200
attctcttac tgtcatgcca tccgtaagat gcttttctgt gactggtgag tactcaacca 4260
agtcattctg agaatagtgt atgcggcgac cgagttgctc ttgcccggcg tcaatacggg 4320
ataataccgc gccacatagc agaactttaa aagtgctcat cattggaaaa cgttcttcgg 4380
ggcgaaaact ctcaaggatc ttaccgctgt tgagatccag ttcgatgtaa cccactcgtg 4440
cacccaactg atcttcagca tcttttactt tcaccagcgt ttctgggtga gcaaaaacag 4500
gaaggcaaaa tgccgcaaaa aagggaataa gggcgacacg gaaatgttga atactcatac 4560
tcttcctttt tcaatattat tgaagcattt atcagggtta ttgtctcatg agcggataca 4620
tatttgaatg tatttagaaa aataaacaaa taggggttcc gcgcacattt ccccgaaaag 4680
tgccacctga cgtc 4694
<210> 114
<211> 10789
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 114
gacattgatt attgactagt tattaatagt aatcaattac ggggtcatta gttcatagcc 60
catatatgga gttccgcgtt acataactta cggtaaatgg cccgcctggc tgaccgccca 120
acgacccccg cccattgacg tcaataatga cgtatgttcc catagtaacg ccaataggga 180
ctttccattg acgtcaatgg gtggagtatt tacggtaaac tgcccacttg gcagtacatc 240
aagtgtatca tatgccaagt acgcccccta ttgacgtcaa tgacggtaaa tggcccgcct 300
ggcattatgc ccagtacatg accttatggg actttcctac ttggcagtac atctacgtat 360
tagtcatcgc tattaccatg gtgatgcggt tttggcagta catcaatggg cgtggatagc 420
ggtttgactc acggggattt ccaagtctcc accccattga cgtcaatggg agtttgtttt 480
ggcaccaaaa tcaacgggac tttccaaaat gtcgtaacaa ctccgcccca ttgacgcaaa 540
tgggcggtag gcgtgtacgg tgggaggtct atataagcag agctggttta gtgaaccgtc 600
agatccgcta gagatccgcg gccgctaata cgactcacta tagggagagc cgccaccatg 660
atcctctggc atgagatgtg gcatgaaggc ctggaagagg catctcgttt gtactttggg 720
gaaaggaacg tgaaaggcat gtttgaggtg ctggagccct tgcatgctat gatggaacgg 780
ggaccccaga ctctgaagga aacatccttt aatcaggcct atggtcgaga tttaatggag 840
gcccaagagt ggtgcaggaa gtacatgaaa tcagggaatg tcaaggacct cacccaagcc 900
tgggacctct attatcatgt gttccgacga atctcaaaga aacggacagc cgacggaagc 960
gagttcgagt caccaaagaa gaagcggaaa gtcgacaaga agtacagcat cggcctggac 1020
atcggcacca actctgtggg ctgggccgtg atcaccgacg agtacaaggt gcccagcaag 1080
aaattcaagg tgctgggcaa caccgaccgg cacagcatca agaagaacct gatcggagcc 1140
ctgctgttcg acagcggcga aacagccgag gccacccggc tgaagagaac cgccagaaga 1200
agatacacca gacggaagaa ccggatctgc tatctgcaag agatcttcag caacgagatg 1260
gccaaggtgg acgacagctt cttccacaga ctggaagagt ccttcctggt ggaagaggat 1320
aagaagcacg agcggcaccc catcttcggc aacatcgtgg acgaggtggc ctaccacgag 1380
aagtacccca ccatctacca cctgagaaag aaactggtgg acagcaccga caaggccgac 1440
ctgcggctga tctatctggc cctggcccac atgatcaagt tccggggcca cttcctgatc 1500
gagggcgacc tgaaccccga caacagcgac gtggacaagc tgttcatcca gctggtgcag 1560
acctacaacc agctgttcga ggaaaacccc atcaacgcca gcggcgtgga cgccaaggcc 1620
atcctgtctg ccagactgag caagagcaga cggctggaaa atctgatcgc ccagctgccc 1680
ggcgagaaga agaatggcct gttcggaaac ctgattgccc tgagcctggg cctgaccccc 1740
aacttcaaga gcaacttcga cctggccgag gatgccaaac tgcagctgag caaggacacc 1800
tacgacgacg acctggacaa cctgctggcc cagatcggcg accagtacgc cgacctgttt 1860
ctggccgcca agaacctgtc cgacgccatc ctgctgagcg acatcctgag agtgaacacc 1920
gagatcacca aggcccccct gagcgcctct atgatcaaga gatacgacga gcaccaccag 1980
gacctgaccc tgctgaaagc tctcgtgcgg cagcagctgc ctgagaagta caaagagatt 2040
ttcttcgacc agagcaagaa cggctacgcc ggctacattg acggcggagc cagccaggaa 2100
gagttctaca agttcatcaa gcccatcctg gaaaagatgg acggcaccga ggaactgctc 2160
gtgaagctga acagagagga cctgctgcgg aagcagcgga ccttcgacaa cggcagcatc 2220
ccccaccaga tccacctggg agagctgcac gccattctgc ggcggcagga agatttttac 2280
ccattcctga aggacaaccg ggaaaagatc gagaagatcc tgaccttccg catcccctac 2340
tacgtgggcc ctctggccag gggaaacagc agattcgcct ggatgaccag aaagagcgag 2400
gaaaccatca ccccctggaa cttcgaggaa gtggtggaca agggcgcttc cgcccagagc 2460
ttcatcgagc ggatgaccaa cttcgataag aacctgccca acgagaaggt gctgcccaag 2520
cacagcctgc tgtacgagta cttcaccgtg tataacgagc tgaccaaagt gaaatacgtg 2580
accgagggaa tgagaaagcc cgccttcctg agcggcgagc agaaaaaggc catcgtggac 2640
ctgctgttca agaccaaccg gaaagtgacc gtgaagcagc tgaaagagga ctacttcaag 2700
aaaatcgagt gcttcgactc cgtggaaatc tccggcgtgg aagatcggtt caacgcctcc 2760
ctgggcacat accacgatct gctgaaaatt atcaaggaca aggacttcct ggacaatgag 2820
gaaaacgagg acattctgga agatatcgtg ctgaccctga cactgtttga ggacagagag 2880
atgatcgagg aacggctgaa aacctatgcc cacctgttcg acgacaaagt gatgaagcag 2940
ctgaagcggc ggagatacac cggctggggc aggctgagcc ggaagctgat caacggcatc 3000
cgggacaagc agtccggcaa gacaatcctg gatttcctga agtccgacgg cttcgccaac 3060
agaaacttca tgcagctgat ccacgacgac agcctgacct ttaaagagga catccagaaa 3120
gcccaggtgt ccggccaggg cgatagcctg cacgagcaca ttgccaatct ggccggcagc 3180
cccgccatta agaagggcat cctgcagaca gtgaaggtgg tggacgagct cgtgaaagtg 3240
atgggccggc acaagcccga gaacatcgtg atcgaaatgg ccagagagaa ccagaccacc 3300
cagaagggac agaagaacag ccgcgagaga atgaagcgga tcgaagaggg catcaaagag 3360
ctgggcagcc agatcctgaa agaacacccc gtggaaaaca cccagctgca gaacgagaag 3420
ctgtacctgt actacctgca gaatgggcgg gatatgtacg tggaccagga actggacatc 3480
aaccggctgt ccgactacga tgtggacgct atcgtgcctc agagctttct gaaggacgac 3540
tccatcgaca acaaggtgct gaccagaagc gacaagaacc ggggcaagag cgacaacgtg 3600
ccctccgaag aggtcgtgaa gaagatgaag aactactggc ggcagctgct gaacgccaag 3660
ctgattaccc agagaaagtt cgacaatctg accaaggccg agagaggcgg cctgagcgaa 3720
ctggataagg ccggcttcat caagagacag ctggtggaaa cccggcagat cacaaagcac 3780
gtggcacaga tcctggactc ccggatgaac actaagtacg acgagaatga caagctgatc 3840
cgggaagtga aagtgatcac cctgaagtcc aagctggtgt ccgatttccg gaaggatttc 3900
cagttttaca aagtgcgcga gatcaacaac taccaccacg cccacgacgc ctacctgaac 3960
gccgtcgtgg gaaccgccct gatcaaaaag taccctaagc tggaaagcga gttcgtgtac 4020
ggcgactaca aggtgtacga cgtgcggaag atgatcgcca agagcgagca ggaaatcggc 4080
aaggctaccg ccaagtactt cttctacagc aacatcatga actttttcaa gaccgagatt 4140
accctggcca acggcgagat ccggaagcgg cctctgatcg agacaaacgg cgaaaccggg 4200
gagatcgtgt gggataaggg ccgggatttt gccaccgtgc ggaaagtgct gagcatgccc 4260
caagtgaata tcgtgaaaaa gaccgaggtg cagacaggcg gcttcagcaa agagtctatc 4320
ctgcccaaga ggaacagcga taagctgatc gccagaaaga aggactggga ccctaagaag 4380
tacggcggct tcgacagccc caccgtggcc tattctgtgc tggtggtggc caaagtggaa 4440
aagggcaagt ccaagaaact gaagagtgtg aaagagctgc tggggatcac catcatggaa 4500
agaagcagct tcgagaagaa tcccatcgac tttctggaag ccaagggcta caaagaagtg 4560
aaaaaggacc tgatcatcaa gctgcctaag tactccctgt tcgagctgga aaacggccgg 4620
aagagaatgc tggcctctgc cggcgaactg cagaagggaa acgaactggc cctgccctcc 4680
aaatatgtga acttcctgta cctggccagc cactatgaga agctgaaggg ctcccccgag 4740
gataatgagc agaaacagct gtttgtggaa cagcacaagc actacctgga cgagatcatc 4800
gagcagatca gcgagttctc caagagagtg atcctggccg acgctaatct ggacaaagtg 4860
ctgtccgcct acaacaagca ccgggataag cccatcagag agcaggccga gaatatcatc 4920
cacctgttta ccctgaccaa tctgggagcc cctgccgcct tcaagtactt tgacaccacc 4980
atcgaccgga agaggtacac cagcaccaaa gaggtgctgg acgccaccct gatccaccag 5040
agcatcaccg gcctgtacga gacacggatc gacctgtctc agctgggagg tgactctgga 5100
ggatctagcg gaggatcctc tggcagcgag acaccaggaa caagcgagtc agcaacacca 5160
gagagcagtg gcggcagcag cggcggcagc agcaccctaa atatagaaga tgagtatcgg 5220
ctacatgaga cctcaaaaga gccagatgtt tctctagggt ccacatggct gtctgatttt 5280
cctcaggcct gggcggaaac cgggggcatg ggactggcag ttcgccaagc tcctctgatc 5340
atacctctga aagcaacctc tacccccgtg tccataaaac aataccccat gtcacaagaa 5400
gccagactgg ggatcaagcc ccacatacag agactgttgg accagggaat actggtaccc 5460
tgccagtccc cctggaacac gcccctgcta cccgttaaga aaccagggac taatgattat 5520
aggcctgtcc aggatctgag agaagtcaac aagcgggtgg aagacatcca ccccaccgtg 5580
cccaaccctt acaacctctt gagcgggctc ccaccgtccc accagtggta cactgtgctt 5640
gatttaaagg atgccttttt ctgcctgaga ctccacccca ccagtcagcc tctcttcgcc 5700
tttgagtgga gagatccaga gatgggaatc tcaggacaat tgacctggac cagactccca 5760
cagggtttca aaaacagtcc caccctgttt aatgaggcac tgcacagaga cctagcagac 5820
ttccggatcc agcacccaga cttgatcctg ctacagtacg tggatgactt actgctggcc 5880
gccacttctg agctagactg ccaacaaggt actcgggccc tgttacaaac cctagggaac 5940
ctcgggtatc gggcctcggc caagaaagcc caaatttgcc agaaacaggt caagtatctg 6000
gggtatcttc taaaagaggg tcagagatgg ctgactgagg ccagaaaaga gactgtgatg 6060
gggcagccta ctccgaagac ccctcgacaa ctaagggagt tcctagggaa ggcaggcttc 6120
tgtcgcctct tcatccctgg gtttgcagaa atggcagccc ccctgtaccc tctcaccaaa 6180
ccggggactc tgtttaattg gggcccagac caacaaaagg cctatcaaga aatcaagcaa 6240
gctcttctaa ctgccccagc cctggggttg ccagatttga ctaagccctt tgaactcttt 6300
gtcgacgaga agcagggcta cgccaaaggt gtcctaacgc aaaaactggg accttggcgt 6360
cggccggtgg cctacctgtc caaaaagcta gacccagtag cagctgggtg gcccccttgc 6420
ctacggatgg tagcagccat tgccgtactg acaaaggatg caggcaagct aaccatggga 6480
cagccactag tcattctggc cccccatgca gtagaggcac tagtcaaaca accccccgac 6540
cgctggcttt ccaacgcccg gatgactcac tatcaggcct tgcttttgga cacggaccgg 6600
gtccagttcg gaccggtggt agccctgaac ccggctacgc tgctcccact gcctgaggaa 6660
gggctgcaac acaactgcct tgatatcctg gccgaagccc acggaacccg acccgaccta 6720
acggaccagc cgctcccaga cgccgaccac acctggtaca cggatggaag cagtctctta 6780
caagagggac agcgtaaggc gggagctgcg gtgaccaccg agaccgaggt aatctgggct 6840
aaagccctgc cagccgggac atccgctcag cgggctgaac tgatagcact cacccaggcc 6900
ctaaagatgg cagaaggtaa gaagctaaat gtttatactg atagccgtta tgcttttgct 6960
actgcccata tccatggaga aatatacaga aggcgtgggt ggctcacatc agaaggcaaa 7020
gagatcaaaa ataaagacga gatcttggcc ctactaaaag ccctctttct gcccaaaaga 7080
cttagcataa tccattgtcc aggacatcaa aagggacaca gcgccgaggc tagaggcaac 7140
cggatggctg accaagcggc ccgaaaggca gccatcacag agactccaga cacctctacc 7200
ctcctcatag aaaattcatc accctctggc ggctcaaaaa gaaccgccga cggcagcgaa 7260
ttcgagccca agaagaagag gaaagtcgag ggcagaggaa gtcttctaac atgcggtgac 7320
gtggaggaga atcccggccc tgctagcggt actagcatgc gtaaaggcga agagctgttc 7380
actggtgtcg tccctattct ggtggaactg gatggtgatg tcaacggtca taagttttcc 7440
gtgcgtggcg agggtgaagg tgacgcaact aatggtaaac tgacgctgaa gttcatctgt 7500
actactggta aactgccggt accttggccg actctggtaa cgacgctgac ttatggtgtt 7560
cagtgctttg ctcgttatcc ggaccatatg aagcagcatg acttcttcaa gtccgccatg 7620
ccggaaggct atgtgcagga acgcacgatt tcctttaagg atgacggcac gtacaaaacg 7680
cgtgcggaag tgaaatttga aggcgatacc ctggtaaacc gcattgagct gaaaggcatt 7740
gactttaaag aagacggcaa tatcctgggc cataagctgg aatacaattt taacagccac 7800
aatgtttaca tcaccgccga taaacaaaaa aatggcatta aagcgaattt taaaattcgc 7860
cacaacgtgg aggatggcag cgtgcagctg gctgatcact accagcaaaa cactccaatc 7920
ggtgatggtc ctgttctgct gccagacaat cactatctga gcacgcaaag cgttctgtct 7980
aaagatccga acgagaaacg cgatcatatg gttctgctgg agttcgtaac cgcagcgggc 8040
atcacgcatg gtatggatga actgtacaaa taagtttaaa cccgctgatc agcctcgact 8100
gtgccttcta gttgccagcc atctgttgtt tgcccctccc ccgtgccttc cttgaccctg 8160
gaaggtgcca ctcccactgt cctttcctaa taaaatgaga aaattgcatc gcattgtctg 8220
agtaggtgtc attctattct ggggggtggg gtggggcagg acagcaaggg ggaggattgg 8280
gaagacaata gcaggcatgc tggggatgcg gtgggctcta tggcttctga ggcggaaaga 8340
accagctggg gctcgatacc gtcgacctct agctagagct tggcgtaatc atggtcatag 8400
ctgtttcctg tgtgaaattg ttatccgctc acaattccac acaacatacg agccggaagc 8460
ataaagtgta aagcctaggg tgcctaatga gtgagctaac tcacattaat tgcgttgcgc 8520
tcactgcccg ctttccagtc gggaaacctg tcgtgccagc tgcattaatg aatcggccaa 8580
cgcgcgggga gaggcggttt gcgtattggg cgctcttccg cttcctcgct cactgactcg 8640
ctgcgctcgg tcgttcggct gcggcgagcg gtatcagctc actcaaaggc ggtaatacgg 8700
ttatccacag aatcagggga taacgcagga aagaacatgt gagcaaaagg ccagcaaaag 8760
gccaggaacc gtaaaaaggc cgcgttgctg gcgtttttcc ataggctccg cccccctgac 8820
gagcatcaca aaaatcgacg ctcaagtcag aggtggcgaa acccgacagg actataaaga 8880
taccaggcgt ttccccctgg aagctccctc gtgcgctctc ctgttccgac cctgccgctt 8940
accggatacc tgtccgcctt tctcccttcg ggaagcgtgg cgctttctca tagctcacgc 9000
tgtaggtatc tcagttcggt gtaggtcgtt cgctccaagc tgggctgtgt gcacgaaccc 9060
cccgttcagc ccgaccgctg cgccttatcc ggtaactatc gtcttgagtc caacccggta 9120
agacacgact tatcgccact ggcagcagcc actggtaaca ggattagcag agcgaggtat 9180
gtaggcggtg ctacagagtt cttgaagtgg tggcctaact acggctacac tagaagaaca 9240
gtatttggta tctgcgctct gctgaagcca gttaccttcg gaaaaagagt tggtagctct 9300
tgatccggca aacaaaccac cgctggtagc ggtggttttt ttgtttgcaa gcagcagatt 9360
acgcgcagaa aaaaaggatc tcaagaagat cctttgatct tttctacggg gtctgacact 9420
cagtggaacg aaaactcacg ttaagggatt ttggtcatga gattatcaaa aaggatcttc 9480
acctagatcc ttttaaatta aaaatgaagt tttaaatcaa tctaaagtat atatgagtaa 9540
acttggtctg acagttacca atgcttaatc agtgaggcac ctatctcagc gatctgtcta 9600
tttcgttcat ccatagttgc ctgactcccc gtcgtgtaga taactacgat acgggagggc 9660
ttaccatctg gccccagtgc tgcaatgata ccgcgagacc cacgctcacc ggctccagat 9720
ttatcagcaa taaaccagcc agccggaagg gccgagcgca gaagtggtcc tgcaacttta 9780
tccgcctcca tccagtctat taattgttgc cgggaagcta gagtaagtag ttcgccagtt 9840
aatagtttgc gcaacgttgt tgccattgct acaggcatcg tggtgtcacg ctcgtcgttt 9900
ggtatggctt cattcagctc cggttcccaa cgatcaaggc gagttacatg atcccccatg 9960
ttgtgcaaaa aagcggttag ctccttcggt cctccgatcg ttgtcagaag taagttggcc 10020
gcagtgttat cactcatggt tatggcagca ctgcataatt ctcttactgt catgccatcc 10080
gtaagatgct tttctgtgac tggtgagtac tcaaccaagt cattctgaga atagtgtatg 10140
cggcgaccga gttgctcttg cccggcgtca atacgggata ataccgcgcc acatagcaga 10200
actttaaaag tgctcatcat tggaaaacgt tcttcggggc gaaaactctc aaggatctta 10260
ccgctgttga gatccagttc gatgtaaccc actcgtgcac ccaactgatc ttcagcatct 10320
tttactttca ccagcgtttc tgggtgagca aaaacaggaa ggcaaaatgc cgcaaaaaag 10380
ggaataaggg cgacacggaa atgttgaata ctcatactct tcctttttca atattattga 10440
agcatttatc agggttattg tctcatgagc ggatacatat ttgaatgtat ttagaaaaat 10500
aaacaaatag gggttccgcg cacatttccc cgaaaagtgc cacctgacgt cgacggatcg 10560
ggagatcgat ctcccgatcc cctagggtct actctcagta caatctgctc tgatgccgca 10620
tagttaagcc agtatctgct ccctgcttgt gtgttggagg tcgctgagta gtgcgcgagc 10680
aaaatttaag ctacaacaag gcaaggcttg accgacaatt gcatgaagaa tctgcttagg 10740
gttaggcgtt ttgcgctgct tcgcgatgta cgggccagat atacgcgtt 10789
<210> 115
<211> 11410
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 115
gacattgatt attgactagt tattaatagt aatcaattac ggggtcatta gttcatagcc 60
catatatgga gttccgcgtt acataactta cggtaaatgg cccgcctggc tgaccgccca 120
acgacccccg cccattgacg tcaataatga cgtatgttcc catagtaacg ccaataggga 180
ctttccattg acgtcaatgg gtggagtatt tacggtaaac tgcccacttg gcagtacatc 240
aagtgtatca tatgccaagt acgcccccta ttgacgtcaa tgacggtaaa tggcccgcct 300
ggcattatgc ccagtacatg accttatggg actttcctac ttggcagtac atctacgtat 360
tagtcatcgc tattaccatg gtgatgcggt tttggcagta catcaatggg cgtggatagc 420
ggtttgactc acggggattt ccaagtctcc accccattga cgtcaatggg agtttgtttt 480
ggcaccaaaa tcaacgggac tttccaaaat gtcgtaacaa ctccgcccca ttgacgcaaa 540
tgggcggtag gcgtgtacgg tgggaggtct atataagcag agctggttta gtgaaccgtc 600
agatccgcta gagatccgcg gccgctaata cgactcacta tagggagagc cgccaccatg 660
acgcgtgtgc ctttgtatgg ttttacttcg atttgtggaa gaagacctga gatggaagct 720
gctgtttcga ctataccaag attccttcaa tcttcctctg gttcgatgtt agatggtcgg 780
tttgatcctc aatccgccgc tcatttcttc ggtgtttacg acggccatgg cggttctcag 840
gtagcgaact attgtagaga gaggatgcat ttggctttgg cggaggagat agctaaggag 900
aaaccgatgc tctgcgatgg tgatacgtgg ctggagaagt ggaagaaagc tcttttcaac 960
tcgttcctga gagttgactc ggagattgag tcagttgcgc cggagacggt tgggtcaacg 1020
tcggtggttg ccgttgtttt cccgtctcac atcttcgtcg ctaactgcgg tgactctaga 1080
gccgttcttt gccgcggcaa aactgcactt ccattatccg ttgaccataa accggataga 1140
gaagatgaag ctgcgaggat tgaagccgca ggagggaaag tgattcagtg gaatggagct 1200
cgtgttttcg gtgttctcgc catgtcgaga tccattggcg atagatactt gaaaccatcc 1260
atcattcctg atccggaagt gacggctgtg aagagagtaa aagaagatga ttgtctgatt 1320
ttggcgagtg acggggtttg ggatgtaatg acggatgaag aagcgtgtga gatggcaagg 1380
aagcggattc tcttgtggca caagaaaaac gcggtggctg gggatgcatc gttgctcgcg 1440
gatgagcgga gaaaggaagg gaaagatcct gcggcgatgt ccgcggctga gtatttgtca 1500
aagctggcga tacagagagg aagcaaagac aacataagtg tggtggtggt tgatttgaag 1560
aaacggacag ccgacggaag cgagttcgag tcaccaaaga agaagcggaa agtcgacaag 1620
aagtacagca tcggcctgga catcggcacc aactctgtgg gctgggccgt gatcaccgac 1680
gagtacaagg tgcccagcaa gaaattcaag gtgctgggca acaccgaccg gcacagcatc 1740
aagaagaacc tgatcggagc cctgctgttc gacagcggcg aaacagccga ggccacccgg 1800
ctgaagagaa ccgccagaag aagatacacc agacggaaga accggatctg ctatctgcaa 1860
gagatcttca gcaacgagat ggccaaggtg gacgacagct tcttccacag actggaagag 1920
tccttcctgg tggaagagga taagaagcac gagcggcacc ccatcttcgg caacatcgtg 1980
gacgaggtgg cctaccacga gaagtacccc accatctacc acctgagaaa gaaactggtg 2040
gacagcaccg acaaggccga cctgcggctg atctatctgg ccctggccca catgatcaag 2100
ttccggggcc acttcctgat cgagggcgac ctgaaccccg acaacagcga cgtggacaag 2160
ctgttcatcc agctggtgca gacctacaac cagctgttcg aggaaaaccc catcaacgcc 2220
agcggcgtgg acgccaaggc catcctgtct gccagactga gcaagagcag acggctggaa 2280
aatctgatcg cccagctgcc cggcgagaag aagaatggcc tgttcggaaa cctgattgcc 2340
ctgagcctgg gcctgacccc caacttcaag agcaacttcg acctggccga ggatgccaaa 2400
ctgcagctga gcaaggacac ctacgacgac gacctggaca acctgctggc ccagatcggc 2460
gaccagtacg ccgacctgtt tctggccgcc aagaacctgt ccgacgccat cctgctgagc 2520
gacatcctga gagtgaacac cgagatcacc aaggcccccc tgagcgcctc tatgatcaag 2580
agatacgacg agcaccacca ggacctgacc ctgctgaaag ctctcgtgcg gcagcagctg 2640
cctgagaagt acaaagagat tttcttcgac cagagcaaga acggctacgc cggctacatt 2700
gacggcggag ccagccagga agagttctac aagttcatca agcccatcct ggaaaagatg 2760
gacggcaccg aggaactgct cgtgaagctg aacagagagg acctgctgcg gaagcagcgg 2820
accttcgaca acggcagcat cccccaccag atccacctgg gagagctgca cgccattctg 2880
cggcggcagg aagattttta cccattcctg aaggacaacc gggaaaagat cgagaagatc 2940
ctgaccttcc gcatccccta ctacgtgggc cctctggcca ggggaaacag cagattcgcc 3000
tggatgacca gaaagagcga ggaaaccatc accccctgga acttcgagga agtggtggac 3060
aagggcgctt ccgcccagag cttcatcgag cggatgacca acttcgataa gaacctgccc 3120
aacgagaagg tgctgcccaa gcacagcctg ctgtacgagt acttcaccgt gtataacgag 3180
ctgaccaaag tgaaatacgt gaccgaggga atgagaaagc ccgccttcct gagcggcgag 3240
cagaaaaagg ccatcgtgga cctgctgttc aagaccaacc ggaaagtgac cgtgaagcag 3300
ctgaaagagg actacttcaa gaaaatcgag tgcttcgact ccgtggaaat ctccggcgtg 3360
gaagatcggt tcaacgcctc cctgggcaca taccacgatc tgctgaaaat tatcaaggac 3420
aaggacttcc tggacaatga ggaaaacgag gacattctgg aagatatcgt gctgaccctg 3480
acactgtttg aggacagaga gatgatcgag gaacggctga aaacctatgc ccacctgttc 3540
gacgacaaag tgatgaagca gctgaagcgg cggagataca ccggctgggg caggctgagc 3600
cggaagctga tcaacggcat ccgggacaag cagtccggca agacaatcct ggatttcctg 3660
aagtccgacg gcttcgccaa cagaaacttc atgcagctga tccacgacga cagcctgacc 3720
tttaaagagg acatccagaa agcccaggtg tccggccagg gcgatagcct gcacgagcac 3780
attgccaatc tggccggcag ccccgccatt aagaagggca tcctgcagac agtgaaggtg 3840
gtggacgagc tcgtgaaagt gatgggccgg cacaagcccg agaacatcgt gatcgaaatg 3900
gccagagaga accagaccac ccagaaggga cagaagaaca gccgcgagag aatgaagcgg 3960
atcgaagagg gcatcaaaga gctgggcagc cagatcctga aagaacaccc cgtggaaaac 4020
acccagctgc agaacgagaa gctgtacctg tactacctgc agaatgggcg ggatatgtac 4080
gtggaccagg aactggacat caaccggctg tccgactacg atgtggacgc tatcgtgcct 4140
cagagctttc tgaaggacga ctccatcgac aacaaggtgc tgaccagaag cgacaagaac 4200
cggggcaaga gcgacaacgt gccctccgaa gaggtcgtga agaagatgaa gaactactgg 4260
cggcagctgc tgaacgccaa gctgattacc cagagaaagt tcgacaatct gaccaaggcc 4320
gagagaggcg gcctgagcga actggataag gccggcttca tcaagagaca gctggtggaa 4380
acccggcaga tcacaaagca cgtggcacag atcctggact cccggatgaa cactaagtac 4440
gacgagaatg acaagctgat ccgggaagtg aaagtgatca ccctgaagtc caagctggtg 4500
tccgatttcc ggaaggattt ccagttttac aaagtgcgcg agatcaacaa ctaccaccac 4560
gcccacgacg cctacctgaa cgccgtcgtg ggaaccgccc tgatcaaaaa gtaccctaag 4620
ctggaaagcg agttcgtgta cggcgactac aaggtgtacg acgtgcggaa gatgatcgcc 4680
aagagcgagc aggaaatcgg caaggctacc gccaagtact tcttctacag caacatcatg 4740
aactttttca agaccgagat taccctggcc aacggcgaga tccggaagcg gcctctgatc 4800
gagacaaacg gcgaaaccgg ggagatcgtg tgggataagg gccgggattt tgccaccgtg 4860
cggaaagtgc tgagcatgcc ccaagtgaat atcgtgaaaa agaccgaggt gcagacaggc 4920
ggcttcagca aagagtctat cctgcccaag aggaacagcg ataagctgat cgccagaaag 4980
aaggactggg accctaagaa gtacggcggc ttcgacagcc ccaccgtggc ctattctgtg 5040
ctggtggtgg ccaaagtgga aaagggcaag tccaagaaac tgaagagtgt gaaagagctg 5100
ctggggatca ccatcatgga aagaagcagc ttcgagaaga atcccatcga ctttctggaa 5160
gccaagggct acaaagaagt gaaaaaggac ctgatcatca agctgcctaa gtactccctg 5220
ttcgagctgg aaaacggccg gaagagaatg ctggcctctg ccggcgaact gcagaaggga 5280
aacgaactgg ccctgccctc caaatatgtg aacttcctgt acctggccag ccactatgag 5340
aagctgaagg gctcccccga ggataatgag cagaaacagc tgtttgtgga acagcacaag 5400
cactacctgg acgagatcat cgagcagatc agcgagttct ccaagagagt gatcctggcc 5460
gacgctaatc tggacaaagt gctgtccgcc tacaacaagc accgggataa gcccatcaga 5520
gagcaggccg agaatatcat ccacctgttt accctgacca atctgggagc ccctgccgcc 5580
ttcaagtact ttgacaccac catcgaccgg aagaggtaca ccagcaccaa agaggtgctg 5640
gacgccaccc tgatccacca gagcatcacc ggcctgtacg agacacggat cgacctgtct 5700
cagctgggag gtgactctgg aggatctagc ggaggatcct ctggcagcga gacaccagga 5760
acaagcgagt cagcaacacc agagagcagt ggcggcagca gcggcggcag cagcacccta 5820
aatatagaag atgagtatcg gctacatgag acctcaaaag agccagatgt ttctctaggg 5880
tccacatggc tgtctgattt tcctcaggcc tgggcggaaa ccgggggcat gggactggca 5940
gttcgccaag ctcctctgat catacctctg aaagcaacct ctacccccgt gtccataaaa 6000
caatacccca tgtcacaaga agccagactg gggatcaagc cccacataca gagactgttg 6060
gaccagggaa tactggtacc ctgccagtcc ccctggaaca cgcccctgct acccgttaag 6120
aaaccaggga ctaatgatta taggcctgtc caggatctga gagaagtcaa caagcgggtg 6180
gaagacatcc accccaccgt gcccaaccct tacaacctct tgagcgggct cccaccgtcc 6240
caccagtggt acactgtgct tgatttaaag gatgcctttt tctgcctgag actccacccc 6300
accagtcagc ctctcttcgc ctttgagtgg agagatccag agatgggaat ctcaggacaa 6360
ttgacctgga ccagactccc acagggtttc aaaaacagtc ccaccctgtt taatgaggca 6420
ctgcacagag acctagcaga cttccggatc cagcacccag acttgatcct gctacagtac 6480
gtggatgact tactgctggc cgccacttct gagctagact gccaacaagg tactcgggcc 6540
ctgttacaaa ccctagggaa cctcgggtat cgggcctcgg ccaagaaagc ccaaatttgc 6600
cagaaacagg tcaagtatct ggggtatctt ctaaaagagg gtcagagatg gctgactgag 6660
gccagaaaag agactgtgat ggggcagcct actccgaaga cccctcgaca actaagggag 6720
ttcctaggga aggcaggctt ctgtcgcctc ttcatccctg ggtttgcaga aatggcagcc 6780
cccctgtacc ctctcaccaa accggggact ctgtttaatt ggggcccaga ccaacaaaag 6840
gcctatcaag aaatcaagca agctcttcta actgccccag ccctggggtt gccagatttg 6900
actaagccct ttgaactctt tgtcgacgag aagcagggct acgccaaagg tgtcctaacg 6960
caaaaactgg gaccttggcg tcggccggtg gcctacctgt ccaaaaagct agacccagta 7020
gcagctgggt ggcccccttg cctacggatg gtagcagcca ttgccgtact gacaaaggat 7080
gcaggcaagc taaccatggg acagccacta gtcattctgg ccccccatgc agtagaggca 7140
ctagtcaaac aaccccccga ccgctggctt tccaacgccc ggatgactca ctatcaggcc 7200
ttgcttttgg acacggaccg ggtccagttc ggaccggtgg tagccctgaa cccggctacg 7260
ctgctcccac tgcctgagga agggctgcaa cacaactgcc ttgatatcct ggccgaagcc 7320
cacggaaccc gacccgacct aacggaccag ccgctcccag acgccgacca cacctggtac 7380
acggatggaa gcagtctctt acaagaggga cagcgtaagg cgggagctgc ggtgaccacc 7440
gagaccgagg taatctgggc taaagccctg ccagccggga catccgctca gcgggctgaa 7500
ctgatagcac tcacccaggc cctaaagatg gcagaaggta agaagctaaa tgtttatact 7560
gatagccgtt atgcttttgc tactgcccat atccatggag aaatatacag aaggcgtggg 7620
tggctcacat cagaaggcaa agagatcaaa aataaagacg agatcttggc cctactaaaa 7680
gccctctttc tgcccaaaag acttagcata atccattgtc caggacatca aaagggacac 7740
agcgccgagg ctagaggcaa ccggatggct gaccaagcgg cccgaaaggc agccatcaca 7800
gagactccag acacctctac cctcctcata gaaaattcat caccctctgg cggctcaaaa 7860
agaaccgccg acggcagcga attcgagccc aagaagaaga ggaaagtcga gggcagagga 7920
agtcttctaa catgcggtga cgtggaggag aatcccggcc ctgctagcgg tactagcatg 7980
cgtaaaggcg aagagctgtt cactggtgtc gtccctattc tggtggaact ggatggtgat 8040
gtcaacggtc ataagttttc cgtgcgtggc gagggtgaag gtgacgcaac taatggtaaa 8100
ctgacgctga agttcatctg tactactggt aaactgccgg taccttggcc gactctggta 8160
acgacgctga cttatggtgt tcagtgcttt gctcgttatc cggaccatat gaagcagcat 8220
gacttcttca agtccgccat gccggaaggc tatgtgcagg aacgcacgat ttcctttaag 8280
gatgacggca cgtacaaaac gcgtgcggaa gtgaaatttg aaggcgatac cctggtaaac 8340
cgcattgagc tgaaaggcat tgactttaaa gaagacggca atatcctggg ccataagctg 8400
gaatacaatt ttaacagcca caatgtttac atcaccgccg ataaacaaaa aaatggcatt 8460
aaagcgaatt ttaaaattcg ccacaacgtg gaggatggca gcgtgcagct ggctgatcac 8520
taccagcaaa acactccaat cggtgatggt cctgttctgc tgccagacaa tcactatctg 8580
agcacgcaaa gcgttctgtc taaagatccg aacgagaaac gcgatcatat ggttctgctg 8640
gagttcgtaa ccgcagcggg catcacgcat ggtatggatg aactgtacaa ataagtttaa 8700
acccgctgat cagcctcgac tgtgccttct agttgccagc catctgttgt ttgcccctcc 8760
cccgtgcctt ccttgaccct ggaaggtgcc actcccactg tcctttccta ataaaatgag 8820
aaaattgcat cgcattgtct gagtaggtgt cattctattc tggggggtgg ggtggggcag 8880
gacagcaagg gggaggattg ggaagacaat agcaggcatg ctggggatgc ggtgggctct 8940
atggcttctg aggcggaaag aaccagctgg ggctcgatac cgtcgacctc tagctagagc 9000
ttggcgtaat catggtcata gctgtttcct gtgtgaaatt gttatccgct cacaattcca 9060
cacaacatac gagccggaag cataaagtgt aaagcctagg gtgcctaatg agtgagctaa 9120
ctcacattaa ttgcgttgcg ctcactgccc gctttccagt cgggaaacct gtcgtgccag 9180
ctgcattaat gaatcggcca acgcgcgggg agaggcggtt tgcgtattgg gcgctcttcc 9240
gcttcctcgc tcactgactc gctgcgctcg gtcgttcggc tgcggcgagc ggtatcagct 9300
cactcaaagg cggtaatacg gttatccaca gaatcagggg ataacgcagg aaagaacatg 9360
tgagcaaaag gccagcaaaa ggccaggaac cgtaaaaagg ccgcgttgct ggcgtttttc 9420
cataggctcc gcccccctga cgagcatcac aaaaatcgac gctcaagtca gaggtggcga 9480
aacccgacag gactataaag ataccaggcg tttccccctg gaagctccct cgtgcgctct 9540
cctgttccga ccctgccgct taccggatac ctgtccgcct ttctcccttc gggaagcgtg 9600
gcgctttctc atagctcacg ctgtaggtat ctcagttcgg tgtaggtcgt tcgctccaag 9660
ctgggctgtg tgcacgaacc ccccgttcag cccgaccgct gcgccttatc cggtaactat 9720
cgtcttgagt ccaacccggt aagacacgac ttatcgccac tggcagcagc cactggtaac 9780
aggattagca gagcgaggta tgtaggcggt gctacagagt tcttgaagtg gtggcctaac 9840
tacggctaca ctagaagaac agtatttggt atctgcgctc tgctgaagcc agttaccttc 9900
ggaaaaagag ttggtagctc ttgatccggc aaacaaacca ccgctggtag cggtggtttt 9960
tttgtttgca agcagcagat tacgcgcaga aaaaaaggat ctcaagaaga tcctttgatc 10020
ttttctacgg ggtctgacac tcagtggaac gaaaactcac gttaagggat tttggtcatg 10080
agattatcaa aaaggatctt cacctagatc cttttaaatt aaaaatgaag ttttaaatca 10140
atctaaagta tatatgagta aacttggtct gacagttacc aatgcttaat cagtgaggca 10200
cctatctcag cgatctgtct atttcgttca tccatagttg cctgactccc cgtcgtgtag 10260
ataactacga tacgggaggg cttaccatct ggccccagtg ctgcaatgat accgcgagac 10320
ccacgctcac cggctccaga tttatcagca ataaaccagc cagccggaag ggccgagcgc 10380
agaagtggtc ctgcaacttt atccgcctcc atccagtcta ttaattgttg ccgggaagct 10440
agagtaagta gttcgccagt taatagtttg cgcaacgttg ttgccattgc tacaggcatc 10500
gtggtgtcac gctcgtcgtt tggtatggct tcattcagct ccggttccca acgatcaagg 10560
cgagttacat gatcccccat gttgtgcaaa aaagcggtta gctccttcgg tcctccgatc 10620
gttgtcagaa gtaagttggc cgcagtgtta tcactcatgg ttatggcagc actgcataat 10680
tctcttactg tcatgccatc cgtaagatgc ttttctgtga ctggtgagta ctcaaccaag 10740
tcattctgag aatagtgtat gcggcgaccg agttgctctt gcccggcgtc aatacgggat 10800
aataccgcgc cacatagcag aactttaaaa gtgctcatca ttggaaaacg ttcttcgggg 10860
cgaaaactct caaggatctt accgctgttg agatccagtt cgatgtaacc cactcgtgca 10920
cccaactgat cttcagcatc ttttactttc accagcgttt ctgggtgagc aaaaacagga 10980
aggcaaaatg ccgcaaaaaa gggaataagg gcgacacgga aatgttgaat actcatactc 11040
ttcctttttc aatattattg aagcatttat cagggttatt gtctcatgag cggatacata 11100
tttgaatgta tttagaaaaa taaacaaata ggggttccgc gcacatttcc ccgaaaagtg 11160
ccacctgacg tcgacggatc gggagatcga tctcccgatc ccctagggtc tactctcagt 11220
acaatctgct ctgatgccgc atagttaagc cagtatctgc tccctgcttg tgtgttggag 11280
gtcgctgagt agtgcgcgag caaaatttaa gctacaacaa ggcaaggctt gaccgacaat 11340
tgcatgaaga atctgcttag ggttaggcgt tttgcgctgc ttcgcgatgt acgggccaga 11400
tatacgcgtt 11410
<210> 116
<211> 351
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 116
atggcttcta actttactca gttcgttctc gtcgacaatg gcggaactgg cgacgtgact 60
gttgccccaa gcaacttcgc taacgggatc gctgaatgga tcagctctaa ctcgcgttca 120
caggcttaca aagtaacctg tagcgttcgt cagagctctg cgcagaatcg caaatacacc 180
atcaaagtcg aggtgcctaa aggcgcctgg cgttcgtact taaatatgga actaaccatt 240
ccaattttcg ccacgaattc cgactgcgag cttattgtta aggcaatgca aggtctccta 300
aaagatggaa acccgattcc ctcagcaatc gcagcaaact ccggcatcta c 351
<210> 117
<211> 705
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 117
gcttctaact ttactcagtt cgttctcgtc gacaatggcg gaactggcga cgtgactgtc 60
gccccaagca acttcgctaa cgggatcgct gaatggatca gctctaactc gcgttcacag 120
gcttacaaag taacctgtag cgttcgtcag agctctgcgc agaatcgcaa atacaccatc 180
aaagtcgagg tgcctaaagg cgcctggcgt tcgtacttaa atatggaact aaccattcca 240
attttcgcca cgaattccga ctgcgagctt attgttaagg caatgcaagg tctcctaaaa 300
gatggaaacc cgattccctc agcaatcgca gcaaactccg gcatctacgc catggccagc 360
aacttcaccc agttcgtgct ggtggacaac ggcggcaccg gcgacgtgac cgtggccccc 420
agcaacttcg ccaacggcat cgccgagtgg atcagcagca acagcagaag ccaggcctac 480
aaggtgacct gcagcgtgag acagagcagc gcccagaaca gaaagtacac catcaaggtg 540
gaggtgccca agggcgcctg gagaagctac ctgaacatgg agctgaccat ccccatcttc 600
gccaccaaca gcgactgcga gctgatcgtg aaggccatgc agggcctgct gaaggacggc 660
aaccccatcc ccagcgccat cgccgccaac agcggcatct acgcc 705
<210> 118
<211> 264
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 118
ggtagtatga aatcaattcg ctgtaaaaac tgcaacaaac tgttatttaa ggcggatagt 60
tttgatcaca ttgaaatcag gtgtccgcgt tgcaaacgtc acatcataat gctgaatgcc 120
tgcgagcatc ccacggagaa acattgtggg aaaagagaaa aaatcacgca ttctgacgaa 180
accgtgcgtt atggctccac tagtgggcac aagcttaatg gcggtggcgg agggatggat 240
gctaagtcac taactgcctg gtcc 264
<210> 119
<211> 561
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 119
atggaccact acctcgacat tcgcttgcga ccggacccgg aatttccccc ggcgcaactc 60
atgagcgtgc tcttcggcaa gctcgcccag gccctggtgg cacagggcgg ggacaggatc 120
ggcgtgagct tccccgacct cgacgaaagc cgctcccggc tgggcgagcg cctgcgcatt 180
catgcctcgg cggacgacct tcgtgccctg ctcgcccggc cctggctgga agggttgcgg 240
gaccatctgc aattcggaga accggcagtc gtgcctcacc ccacaccgta ccgtcaggtc 300
agtcgggttc aggcgaaaag caatccggaa cgcctgcggc ggcggctcat gcgccggcac 360
gatctgagtg aggaggaggc tcggaaacgc attcccgata cggtcgcgag agccttggac 420
ctgcccttcg tcacgctacg cagccagagc accggacagc acttccgtct cttcatccgc 480
cacgggccgt tgcaggtgac ggcagaggaa ggaggattca cctgttacgg gttgagcaaa 540
ggaggtttcg ttccctggtt c 561
<210> 120
<211> 369
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 120
atgggttcca aaaccatcgt tctttcggtc ggcgaggcta ctcgcactct gactgagatc 60
cagtccaccg cagaccgtca gatcttcgaa gagaaggtcg ggcctctggt gggtcggctg 120
cgcctcacgg cttcgctccg tcaaaacgga gccaagaccg cgtatcgcgt caacctaaaa 180
ctggatcagg cggacgtcgt tgattccgga cttccgaaag tgcgctacac tcaggtatgg 240
tcgcacgacg tgacaatcgt tgcgaatagc accgaggcct cgcgcaaatc gttgtacgat 300
ttgaccaagt ccctcgtcgc gacctcgcag gtcgaagatc ttgtcgtcaa ccttgtgccg 360
ctgggccgt 369
<210> 121
<211> 741
<212> DNA
<213> Artificial sequence (Artificial Sequence)
<400> 121
tccaaaacta tcgttctgag cgtaggtgaa gcgaccagaa cgttaactga aattcaatct 60
acagcagaca ggcaaatatt tgaagagaaa gtcggtccat tagtagggag gttaagattg 120
acagctagct taagacaaaa tggagctaaa actgcataca gggtcaattt aaaattggat 180
caagcagatg tcgttgatag cggtctacct aaggttagat acacgcaagt gtggtcacac 240
gatgtcacta ttgtcgcgaa ttctaccgaa gctagtagaa aatcattgta tgatttaaca 300
aaatccttgg tggctacctc tcaggtggaa gatcttgttg tgaatttagt tccattaggt 360
agggcggacc cgctagcctc caaaaccatc gttctttcgg tcggcgaggc tactcgcact 420
ctgactgaga tccagtccac cgcagaccgt cagatcttcg aagagaaggt cgggcctctg 480
gtgggtcggc tgcgcctcac ggcttcgctc cgtcaaaacg gagccaagac cgcgtatcgc 540
gtcaacctaa aactggatca ggcggacgtc gttgattccg gacttccgaa agtgcgctac 600
actcaggtat ggtcgcacga cgtgacaatc gttgcgaata gcaccgaggc ctcgcgcaaa 660
tcgttgtacg atttgaccaa gtccctcgtc gcgacctcgc aggtcgaaga tcttgtcgtc 720
aaccttgtgc cgctgggccg t 741

Claims (14)

1. A gene leader editing system comprising a vector comprising a gene encoding sgRNA, a gene encoding an isolated leader RNA, and a gene encoding a fusion protein, wherein the isolated leader RNA comprises a reverse transcription template RTT, a primary binding site PBS, an RNA stem loop structure.
2. The system of claim 1, wherein the fusion protein is a fusion protein of the RNA binding protein RBP, cas9 nickase or a variant thereof, or reverse transcriptase; alternatively, the fusion protein comprises: a first fusion protein comprising an RNA-binding protein RBP and a first inducible binding molecule, and a second fusion protein fragment comprising a Cas9 nickase or a variant thereof, a reverse transcriptase, a second inducible binding molecule.
3. The system of claim 1, wherein the RNA stem loop structure is selected from at least one of:
1) MS2, PP7, comBS, csy4BS and box B with sequences shown in SEQ ID NO. 1-5 respectively;
2) An RNA sequence obtained by adding one or more nucleotides to the 5 'end and/or the 3' end of 1);
3) An RNA sequence having an identity of 85% or more to the RNA sequence of 1) or 2).
4. The system of claim 1, wherein at least one selected from the group consisting of:
1) The RNA stem-loop structure is linked to the 3 'end of the primary binding site PBS, and/or the 5' end of the reverse transcription template RTT;
2) The separated precursor RNA sequentially comprises a reverse transcription template RTT, a main binding site PBS and an RNA stem loop structure from a 5 'end to a 3' end;
3) The separated lead RNA sequentially comprises an RNA stem loop structure, a reverse transcription template RTT and a main binding site PBS from the 5 'end to the 3' end;
4) The isolated guide RNA is linear or circular;
5) The RBP is a protein which specifically binds to an RNA stem-loop structure; the RBP is one or more;
6) The carrier is one or more;
7) The gene encoding the sgRNA, the gene encoding the isolated leader RNA and the gene encoding the fusion protein are one or more;
8) The gene for encoding the sgRNA, the gene for encoding the isolated leader RNA and the gene for encoding the fusion protein are positioned on the same carrier or different carriers;
9) The first induced binding molecule and the second induced binding molecule are molecules suitable for binding by the induced molecules;
10 The first inducible binding molecule is located at the N-terminus or the C-terminus of RBP;
11 The second fusion protein fragment comprises a second induced binding molecule, cas9 or a variant thereof and reverse transcriptase from the N end to the C end in sequence; or, the second fusion protein fragment comprises Cas9 or a variant thereof, reverse transcriptase, and a second inducible binding molecule in order from the N-terminus to the C-terminus.
5. The system of claim 4, selected from any one of the following:
1) The RBP is selected from any one of tdMCP, tdPCP, COM, csy H29A, N p;
2) The Cas9 nickase is H840A;
3) The reverse transcriptase is MMLV;
3) The first induction molecule and the second induction molecule are respectively and independently selected from two pairs of proteins FKBP and FRB or ABI and PYL 1;
4) The system also contains a selectable marker protein.
6. An isolated leader RNA, characterized in that the isolated leader RNA is the isolated leader RNA of any one of the systems of claims 1 to 5.
7. A fusion protein comprising an RNA binding protein RBP and a first induced binding molecule, or alternatively, a Cas9 nickase or a variant thereof, a reverse transcriptase, and a second induced binding molecule.
8. The fusion protein of claim 7, selected from at least any one of the following:
1) The first induced binding molecule and the second induced binding molecule are molecules suitable for binding by the induced molecules;
2) The first induction molecule and the second induction molecule are respectively and independently selected from one of two pairs of proteins FKBP and FRB or ABI and PYL 1;
3) The Cas9 nickase is H840A;
4) The reverse transcriptase is MMLV.
9. A nucleic acid encoding the isolated leader RNA of claim 6 and/or the fusion protein of claim 7 or 8.
10. A construct comprising the nucleic acid of claim 9.
11. A host cell comprising the construct or genome of claim 10 integrated with an exogenous nucleic acid of claim 9.
12. Use of the system of any one of claims 1-5 or the isolated guide RNA of claim 6 or the fusion protein of claim 7 or 8 or the nucleic acid of claim 9 or the construct of claim 10 or the host cell of claim 11 for at least one of:
1) Editing genomic sequences for an organism or a biological cell;
2) An edited product for preparing a genomic sequence of an organism or a biological cell;
3) For improving the efficiency of editing genomic sequences of an organism or a biological cell;
4) For the preparation of products which increase the efficiency of editing of genomic sequences of organisms or biological cells.
13. The use according to claim 12, for DNA editing or RNA editing; preferably for DNA editing; further preferably, for editing of runx1_ +5 site;
even more preferably, for editing of runx1_ +5g·c to t·a.
14. A method of gene editing comprising introducing the system of any one of claims 1-5 or the isolated guide RNA of claim 6 or the fusion protein of claim 7 or 8 or the nucleic acid of claim 9 or the construct of claim 10 or the host cell of claim 11 into a body to be edited to effect editing of a gene.
CN202210114825.0A 2022-01-30 2022-01-30 Adjustable pilot editor and application thereof Pending CN116555335A (en)

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