Chimeric HPV-NG compositions and methods of use thereof
Chimeric HPV compositions, incorporating a peptide mimic from Neisseria gonorrhoeae, offer a cost-effective solution for preventing HPV and gonorrhea infections by inducing immune responses against both pathogens, addressing the accessibility issues of current HPV vaccines.
Patent Information
- Application Number
- PCT/US2024/045541
- Authority / Receiving Office
- WO · WO
- Patent Type
- Applications
- Current Assignee / Owner
- Priority Date
- 2023-09-08
- Filing Date
- 2024-09-06
- Publication Date
- 2025-03-13
AI Technical Summary
Current HPV vaccines are expensive, making them inaccessible in developing countries, and there is a need for a more cost-effective method to produce vaccines that can effectively prevent HPV and gonorrhea infections, especially in regions where coinfection rates are high.
Development of chimeric HPV compositions that include a chimeric polypeptide comprising an HPV polypeptide and a peptide mimic derived from Neisseria gonorrhoeae, which can be used to create virus-like particles (VLPs) for vaccine production. These VLPs are designed to induce immune responses and prevent infections from both HPV and N. gonorrhoeae.
The chimeric HPV compositions effectively induce immune responses, including antibody production, which can lead to the clearance of both HPV and N. gonorrhoeae, providing protection against dual infections. This approach has the potential to be more cost-effective than traditional vaccine production methods, making it suitable for use in developing countries.
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Figure US2024045541_13032025_PF_FP_ABST
Abstract
Description
[0001] CHIMERIC HPV-NG COMPOSITIONS AND METHODS OF USE THEREOF
[0002] CROSS-REFERENCE TO RELATED APPLICATION
[0003] This application claims priority to, and the benefit of, U.S. Provisional Patent Application No. 63 / 581,312, filed September 8, 2023, which is incorporated by reference herein in its entirety.
[0004] STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH
[0005] This invention was made with government support under AI167283 awarded by the National Institutes of Health. The government has certain rights in the invention.
[0006] REFERENCE TO SEQUENCE LISTING
[0007] The sequence listing submitted on September 6, 2024, as an .XML file entitled “11579- 007W01_ST26” created on September 4, 2024, and having a file size of 217,526 bytes is hereby incorporated by reference pursuant to 37 C.F.R. § 1.52(e)(5).
[0008] FIELD
[0009] The present disclosure relates to chimeric human papillomavirus (HPV) compositions for use in preventing infectious diseases. The present disclosure also relates to methods of generating chimeric HPV compositions.
[0010] BACKGROUND
[0011] Cervical cancer is the fourth most prevalent cancer in women globally, with an estimated 604 000 reported cases in 2020. Approximately 95% of cervical cancer cases are a result of genital lesions which are caused by human papillomavirus (HPV) infections. Neisseria gonorrhoeae (Ng) is the bacteria which causes approximately 87 million gonorrhea infections per year. The risk of cervical lesions progressing to cancer is increased with coinfection of N. gonorrhoeae and HPV. While great success has been achieved by existing HPV vaccines, vaccine production is expensive, and a more cost-effective method is needed to produce vaccines for developing countries.
[0012] Given limitations of producing HPV vaccines, there is a need to address the aforementioned problems mentioned above by creating a preventative treatment targeting HPV infections, gonorrhea infection, or both. The compounds, compositions, and methods disclosed herein address these and other needs.
[0013] SUMMARY
[0014] The present disclosure provides compositions comprising a chimeric polypeptide comprising an HPV polypeptide and a peptide mimic derived from Neisseria gonorrhoeae. The present disclosure also provides methods using the chimeric polypeptide to induce immune responses and prevent infections from HPV, N. gonorrhoeae, or combinations thereof.
[0015] In one aspect, disclosed herein is a human papillomavirus (HPV) virus-like particle (VLP) comprising a chimeric polypeptide comprising an HPV polypeptide and a peptide mimic derived from Neisseria gonorrhoeae (N. gonorrhoeae).
[0016] In one aspect, disclosed herein is a vaccine comprising a human papillomavirus (HPV) virus-like particle (VLP), wherein the HPV VLP comprises a chimeric polypeptide comprising the HPV polypeptide and the peptide mimic derived from Neisseria gonorrhoeae (N. gonorrhoeae) of any preceding aspect, and a pharmaceutically acceptable carrier selected from an excipient, a diluent, a salt, a buffer, a stabilizer, a lipid, or an emulsion.
[0017] In some embodiments, the chimeric polypeptide comprises at least 70% identity to SEQ ID NO: 2, or derivatives thereof. In some embodiments, the chimeric polypeptide comprises at least 75% identity to SEQ ID NO: 2, or derivatives thereof. In some embodiments, the chimeric polypeptide comprises at least 80% identity to SEQ ID NO: 2, or derivatives thereof. In some embodiments, the chimeric polypeptide comprises at least 85% identity to SEQ ID NO: 2, or derivatives thereof. In some embodiments, the chimeric polypeptide comprises at least 90% identity to SEQ ID NO: 2, or derivatives thereof. In some embodiments, the chimeric polypeptide comprises at least 95% identity to SEQ ID NO: 2, or derivatives thereof. In some embodiments, the chimeric polypeptide comprises at least 99% identity to SEQ ID NO: 2, or derivatives thereof. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 2, or derivatives thereof. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 2.
[0018] In some embodiments, the chimeric polypeptide is encoded by a nucleic acid sequence comprising at least 70% sequence identity to SEQ ID NO: 1, or derivatives thereof. In some embodiments, the chimeric polypeptide is encoded by a nucleic acid sequence comprising at least 75% sequence identity to SEQ ID NO: 1, or derivatives thereof. In some embodiments, the chimeric polypeptide is encoded by a nucleic acid sequence comprising at least 80% sequence identity to SEQ ID NO: 1, or derivatives thereof. In some embodiments, the chimeric polypeptide is encoded by a nucleic acid sequence comprising at least 85% sequence identity to SEQ ID NO: 1, or derivatives thereof. In some embodiments, the chimeric polypeptide is encoded by a nucleic acid sequence comprising at least 90% sequence identity to SEQ ID NO: 1, or derivatives thereof. In some embodiments, the chimeric polypeptide is encoded by a nucleic acid sequence comprising at least 95% sequence identity to SEQ ID NO: 1, or derivatives thereof. In some embodiments, the chimeric polypeptide is encoded by a nucleic acid sequence comprising at least 99% sequence identity to SEQ ID NO: 1, or derivatives thereof. In some embodiments, the chimeric polypeptide is encoded by a nucleic acid sequence comprising SEQ ID NO: 1, or derivatives thereof. In some embodiments, the chimeric polypeptide is encoded by a nucleic acid sequence comprising SEQ ID NO: 1.
[0019] In some embodiments, the peptide mimic comprises a 2C7 peptide. In some embodiments, the peptide mimic comprises SEQ ID NO: 21, SEQ ID NO: 23, or derivatives thereof. In some embodiments, the peptide mimic is encoded by a nucleic acid sequence comprising SEQ ID NO: 22, SEQ ID NO: 24, or derivatives thereof.
[0020] In some embodiments, the peptide mimic comprises an epitope.
[0021] In some embodiments, the HPV polypeptide comprises SEQ ID NO: 20, or derivatives thereof. In some embodiments, the HPV polypeptide is encoded by a nucleic acid comprising SEQ ID NO: 19, or derivatives thereof.
[0022] In some embodiments, the HPV polypeptide is derived from an HPV 16 virus.
[0023] In some embodiments, the peptide mimic is inserted into the HPV polypeptide. In some embodiments, the peptide mimic is inserted into an LI capsid peptide. In some embodiments, the LI capsid peptide comprises a DE loop. In some embodiments, the peptide mimic is inserted between amino acids 131 and 132 of the DE loop.
[0024] In one aspect, disclosed herein is a method of inducing an immune response to a human papillomavirus (HPV), Neisseria gonorrhoeae (N. gonorrhoeae), or combinations thereof, the method comprising administering to a subject an HPV virus-like particle (VLP) vaccine comprising the chimeric polypeptide of any preceding aspect and a pharmaceutically acceptable carrier selected from an excipient, a diluent, a salt, a buffer, a stabilizer, a lipid, or an emulsion.
[0025] In some embodiments, the immune response comprises an antibody response against an N. gonorrhoeae bacterium, a human papillomavirus, or combination thereof. In some embodiments, the immune response comprises clearance of the N. gonorrhoeae bacterium, the human papillomavirus, or combination thereof.
[0026] In one aspect, disclosed herein is a method of preventing an infection from a human papillomavirus (HPV), Neisseria gonorrhoeae (N. gonorrhoeae), or combinations thereof, the method comprising administering to a subject a vaccine comprising an HPV virus-like particle (VLP) comprising chimeric polypeptide of any preceding aspect and a pharmaceutically acceptable carrier selected from an excipient, a diluent, a salt, a buffer, a stabilizer, a lipid, or an emulsion.
[0027] In some embodiments, the method induces an immune response against an N. gonorrhoeae bacterium, a human papillomavirus, or combination thereof. In some embodiments, the immune response comprises an antibody response to or a clearance of the N. gonorrhoeae bacterium, the human papillomavirus, or combination thereof.
[0028] In one aspect, disclosed herein is a method of producing the HPV VLP of any preceding aspect, the method comprising generating a chimeric nucleic acid sequence by inserting a first nucleic acid sequence encoding the peptide mimic into a second nucleic acid sequence encoding the HPV polypeptide, transferring the chimeric nucleic acid sequence into a plant expression vector, infiltrating the plant expression vector of step b) into a tobacco plant, expressing the HPV VLP in the tobacco plant, wherein the HPV VLP comprises a chimeric polypeptide, and purifying the HPV VLP from the tobacco plant.
[0029] In some embodiments, the chimeric polypeptide comprises an HPV polypeptide and a peptide mimic derived from N. gonorrhoeae. In some embodiments, the first nucleic acid sequence comprises SEQ ID NO: 22 SEQ ID NO: 24, or derivatives thereof. In some embodiments, the second nucleic acid sequence comprises SEQ ID NO: 19, or derivatives thereof.
[0030] In some embodiments, the plant expression vector comprises SEQ ID NO: 17, SEQ ID NO: 18, or derivatives thereof. In some embodiments, the plant expression vector comprises a pTRAkc-rbcsl-cTP vector or a pRIC3 vector. In some embodiments, the plant expression vector comprises a chloroplast-specific targeting sequence.
[0031] In some embodiments, the plant expression vector is infiltrated into the tobacco plant using an Agro actenwm-mediated gene transfer method. In some embodiments, the chimeric HPV VLP is purified by ultracentrifugation through an iodixanol density gradient. In some embodiments, the tobacco plant comprises Nicotiana benthamiana (N. benthamiana). In some embodiments, the method comprises a 2C7 peptide mimic. In some embodiments, the method comprises the HPV polypeptide derived from an HPV 16 virus.
[0032] In one aspect, disclosed herein is a plant expression vector comprising a nucleic acid sequence encoding a chimeric polypeptide comprising an HPV polypeptide and a peptide mimic derived from N. Gonorrhoeae, wherein the plant expression vector comprises at least 70% identity to SEQ ID NO: 25, SEQ ID NO: 29, or derivatives thereof.
[0033] In some embodiments, the plant expression vector and the nucleic acid sequence comprise at least 80% identity to SEQ ID NO: 25, SEQ ID NO: 29, or derivatives thereof. In some embodiments, the plant expression vector and the nucleic acid sequence comprise at least 90% identity to SEQ ID NO: 25, SEQ ID NO: 29, or derivatives thereof. In some embodiments, the plant expression vector and the nucleic acid sequence comprise SEQ ID NO: 25, SEQ ID NO: 29, or derivatives thereof.
[0034] In some embodiments, the nucleic acid sequence comprises SEQ ID NO: 22, SEQ ID NO: 24, or derivatives thereof, inserted into SEQ ID NO: 19, or derivatives thereof. In some embodiments, the plant expression vector comprises a pTRAkc-rbcsl-cTP vector or a pRIC3 vector. In some embodiments, the plant expression vector comprises a chloroplast-specific targeting sequence.
[0035] BRIEF DESCRIPTION OF FIGURES
[0036] The accompanying figures, which are incorporated in and constitute a part of this specification, illustrate several aspects described below.
[0037] FIGS. 1A and IB show the schematic of HPV- 16 LL2C7 gene design. FIG. 1A shows the LI monomer showing different surface loops (letters) - circled in red are DE loop and h4 helix surface loops (Image from Chen et al. (2000)). FIG. IB shows the insertion or substitution positions in HPV- 16 LI to create generation I and generation II constructs. (_i) indicates insertion, (_s) indicates substitution. Not drawn to scale.
[0038] FIG. 2 shows the phenotype of N. benthamiana harvested four days post-infiltration with gen I constructs.
[0039] FIGS. 3A and 3B show the anti-Ll and anti-2C7 western blots of crude extracts. FIG. 3A shows the LI protein (56 kDa , red arrow) detected with Camvir-1 mAh (1:15000). FIG. 3B shows the 2C7 peptide (as chimera with LI ~56kDa, red arrow) detected with anti-2C7 mAb (1 :50). Labels: -, infiltration media negative; M, molecular weight marker (kDa); 1) CTP L1 :2C7 DE i; 2) CTP L1:2C7 DE s; 3) CTP LE2C7 h4_i; 4) CTP LE2C7 h4_s; 5) pRIC3 LI :2C7 DE s; 6) pRIC3 L1:2C7 DE_i; 7) pRIC3 L1:2C7 h4_s; +. HPV-16 LI positive control.
[0040] FIG. 4 shows transmission electron microscopy micrographs of CTP L1:2C7 h4_i VLPs. Crude samples were applied to carbon coated grids and negatively stained with 2% uranyl acetate. Blue arrows - VLPs 40-55nm. Magnification 27500x.
[0041] FIGS. 5A, 5B, 5C, and 5D show the anti-Ll and anti-2C7 western blots of purified CTP L1:2C7 h4_i and pRIC3 L1:2C7 h4_s constructs. FIGS. 5A and 5B show the LI protein (56 kDa , red arrow) detected with Camvir-1 mAb (1:15000). FIGS. 5C and 5D show the 2C7 peptide detected with anti-2C7 mAb (1:50). Labels: M, molecular weight marker (kDa); CE, crude extract; F1-F6, purified fractions; +, HPV-16 LI positive control; +1, octa2C7 peptide positive control; +2, LOS peptide positive control; : infiltration media negative control.
[0042] FIG. 6 shows the transmission electron micrographs of purified CTP L1:2C7 h4_i and pRIC3 L1:2C7 h4_s fractions. Samples were applied to carbon coated grids and negatively stained with 2% uranyl acetate. Magnification 27500x or 44000x.
[0043] FIGS. 7A and 7B show the characterization of 2C7 peptide display by indirect ELISA. Binding of 2C7 mAb to CTP L1:2C7 h4_i VLPs (FIG. 7A) and pRIC3 L1:2C7 h4_s VLPs (FIG. 7B).
[0044] FIGS. 8 A, 8B, 8C, and 8D show the HPV-Ng generation I chimaera expression time trials in N. benlhamiana. L1:2C7 DE_i (FIG. 8A), LL2C7 DE_s (FIG. 8B), L1:2C7 h4_i (FIG. 8C) and L1:2C7 h4_s (FIG. 8D). LI protein (56 kDa , red arrow) was detected with Camvir-1 mAb (1:15000). Labels: dpi, days post-infiltration; M, molecular weight marker (kDa); +, HPV-16 LI positive control.
[0045] FIGS. 9 A and 9B show the dot blot of denatured and non-denatured HPV-Vg chimeras. Crude extracts of all chimeras harvested 3 (FIG. 9A) or 5 dpi (FIG. 9B). Membranes were probed with anti-2C7 mAb (1:50). Labels: 1) CTP LL2C7 DE_i; 2) CTP LL2C7 DE s; 3) CTP LL2C7 h4 i; 4) CTP L1 :2C7 h4_s; 5) pRIC3 LL2C7 DE_i; 6) pRIC3 LL2C7 DE_s; 7) pRIC3 L1 :2C7 h4_i; 8) pRIC3 L1 :2C7 h4_s; LOS positive, LOS peptide positive control.
[0046] FIG. 10 shows the phenotype of N. benthamiana plants harvested 5 days postinfiltration with CTP gen I constructs.
[0047] FIGS. 11A, 11B, 11C, and 11D show the anti-Ll western blot of purified CTP generation I constructs. LL2C7 DE_i (FIG. 11 A), L1:2C7 DE_s (FIG. 11B), L1:2C7 h4_i (FIG. 11C) and L1:2C7 h4_s (FIG. 11D). LI protein (56 kDa , red arrow) was detected with Camvir-1 mAb (1 : 15000). Labels: M, molecular weight marker (kDa); CE, crude extract; FIF6. purified fractions; +, HPV-16 LI positive control.
[0048] FIG. 12 shows the dot blot of purified eTP generation I constructs. The 2C7 peptide was probed with anti-2C7 mAh (1 :50). Labels: CE, crude extract; F1-F6, purified fractions; LOS positive, LOS peptide positive control.
[0049] FIG. 13 shows the transmission electron micrographs of purified CTP LL2C7 h4_i and pRlC3 L1:2C7 h4_s fractions, samples were applied to carbon coated grids and negatively stained with 2% uranyl acetate. Red arrows - VLPs 35-55 nm Mag: 27500 x.
[0050] FIGS. 14A, 14B, 14C, 14D, and 14E show the western and dot blot of purified CTP generation I constructs. LL2C7 DE_i (FIG. 14A), L1:2C7 DE_s (FIG. 14B), LL2C7 h4_i (FIG. 14C), L1:2C7 h4_s (FIG. 14D) and anti-2C7 (FIG. 14E) dot blot of all constructs. LI protein (56 kDa , red arrow) was detected with Camvir-1 mAb (1: 15000). 2C7 peptide was detected with anti-2C7 mAb (1:50). Labels: M, molecular weight marker (kDa); CE, crude extract; 30%, dialyzed cushion sample; F1-F6, purified fractions; +, HPV-16 LI positive control; LOS positive, LOS positive control.
[0051] FIG. 15 shows the transmission electron micrographs of purified CTP generation I constructs. Purified fractions were applied to carbon coated grids and negatively stained with 2% uranyl acetate. Mag: 44000 x.
[0052] FIG. 16 shows the phenotype of N. benthamiana plants harvested 5 days postinfiltration with eTP and pRIC3 gen II constructs.
[0053] FIGS. 17A, 17B, 17C, 17D, 17E, 17F, and 17G show the anti-Ll western blot of purified CTP and pRIC3 generation II constructs. CTP L1:2C7 DE_i (FIG. 17 A), pRIC3 LL2C7 DE-i (FIG. 17B), CTP LL2C7 DE_s (FIG. 17C), pRIC3 LL2C7 DE_s (FIG. 17D), CTP LL2C7 h4_i (FIG. 17E), pRIC3 LL2C7 h4_i (FIG. 17F) and CTP LL2C7 h4_s (FIG. 17G). LI protein (56 kDa , red arrow) was detected with Camvir-1 mAb (1: 15000). Labels: M, molecular weight marker (kDa); CE, crude extract; F1-F6, purified fractions; +, HPV-16 LI positive control.
[0054] FIG. 18 shows the dot blot of purified eTP and pRIC3 generation II constructs. The 2C7 peptide was probed with anti-2C7 mAb (1:50). Labels: F1-F6, purified fractions; LOS positive, LOS peptide positive control.
[0055] FIGS. 19A and 19B show the transmission electron micrographs of purified eTP and pRIC3 generation II constructs. Purified fractions were applied to carbon coated grids and negatively stained with 2% uranyl acetate. Mag: 27500 and 44000 x. FIG. 20 shows the phenotype of N. benthamiana plants harvested 5 days postinfiltration.
[0056] FIGS. 21 A and 21B show the detection of LI and 2C7 proteins in CTP L1:2C7 DE_i, CTP hLl and CTP empty vector. FIG. 21A shows the anti-Ll western blots of purified fractions. LI protein (56 kDa, red arrow) detected with Camvir-1 mAb (1:15000). FIG. 21B shows the anti- 2C7 dot blots of purified fractions. 2C7 protein detected with anti-2C7 mAb (1:50). Labels: M. molecular weight marker (kDa); CE, crude extract; 30%. cushion fraction; F1-F5, purified fractions; +, HPV-16 LI positive control; LOS+, LOS peptide positive control.
[0057] FIGS. 22A, 22B, and 22C show the transmission electron micrographs of CTP LL2C7 DE_i, CTP hLl, and CTP empty vector. Samples were applied to carbon coated grids and negatively stained with 2% uranyl acetate. Mag: 40000 x.
[0058] FIGS. 23A and 23B show the characterization of 2C7 peptide display and V5 epitope display by indirect ELISA. Plates were coated with 100 uL of purified fractions 2-4 of CTP LL2C7 DE_i, CTP hLl and CTP empty vector, at a 1 / 10 and 1 / 100 dilution. Primary antibodies: anti-2C7 mAb (1:200) or H16.V5 mAb (1:5000). Secondary antibody: anti-mouse IgG (1: 10000).
[0059] FIGS. 24A and 24B show the quantitation of LL2C7 DE_i VLPs Coomassie stained SDS-PAGE of concentrated band and sample above the band. FIG. 24B shows the western blot of fraction before and after banding. Labels: M, molecular weight marker (kDa); F2T, sample above F2 band; F2B, band sample, F3T, sample above F3 band; F3B, band sample; F2-F5, fractions before banding; +, LI positive control; LI protein (56 kDa, red arrow).
[0060] FIG. 25 shows the transmission electron micrographs of concentrated CTP LL2C7 DE_i. Samples were applied to carbon coated grids and negatively stained with 2% uranyl acetate. Mag: 40000 x.
[0061] FIG. 26 shows the detection of LI and 2C7 proteins in CTP L1:2C7 DE_i. Anti-Ll western blots and anti-2C7 dot blots of purified fractions. LI protein (56 kDa, red arrow) detected with Camvir-1 mAb (1:15000). 2C7 protein detected with anti-2C7 mAb (1:50). Labels: M, molecular weight marker (kDa); CE, crude extract; 30%, cushion fraction; F1-F5, purified fractions; +, HPV-16 LI positive control; LOS+, LOS peptide positive control.
[0062] FIG. 27 shows the banding of cVLPs. Pooled fractions 2-4 were loaded onto a 50% iodixanol cushion and centrifuged at 174 500 xg for 3.5 h in a SW32Ti rotor. Red arrows - bands removed with a needle and syringe, followed by fractionation of the tube from the bottom. FIG. 28 shows the anti-Ll and anti-2C7 dot blots of sampled bands and fractions. LI protein was detected with Camvir-1 mAb (1:15000). 2C7 protein detected with anti-2C7 mAb (1:50). Labels: 1-13, fractions collected from the bottom of the tube: 1.1 - 2.4, bands collected from each tube; LOS+, LOS peptide positive control.
[0063] FIG. 29 shows the quantitation of LL2C7 DE_i VLPs. Coomassie stained SDS-PAGE of concentrated band and sample above the band. Labels: M, molecular weight marker (kDa); 30% 1 and 30% 2, 30% cushion fraction from purification batch 1 and 2; 1.1 - 2.4, bands collected from each tube; Red arrow, expected band size.
[0064] FIG. 30 shows the quantitation of L1:2C7 DE_i VLPs. Coomassie stained SDS-PAGE and ponceau stained nitrocellulose membranes of pelleted cVLPs. M, molecular weight marker (kDa); Pl, pellet batch 1, Pl 1 / 50. pelleted 1 dilution; P2. pellet batch 2; F2, F3, fractions; red arrow, expected band size.
[0065] FIG. 31 shows the BCA protein quantification of batch 1 and batch 2 cVLPs.
[0066] FIG. 32 shows the Transmission electron micrographs of L1:2C7 DE_i VLPs. Samples were applied to carbon coated grids and negatively stained with 2% uranyl acetate. Mag: 40000x.
[0067] FIGS. 33A, 33B, and 33C show the anti-Ll western blot and Anti-Rubisco western blot and anti-2C7 dot blot of purified VLPs. LI protein (57 kDa , black arrow) was detected with anti-Ll Camvir-1 mAb (1 : 5000). Labels: M, molecular weight marker (kDa); Chimera; HPV16 L 1 positive control; empty vector negative control. 2C7 peptide was probed with anti-2C7 mAb (1:200). Labels: purified chimera; HPV16 LI and Empty vector as negative controls; Octa 2C7 peptide and LOS positive controls.
[0068] FIGS. 34A, 34B, and 34C show the transmission electron micrographs of purified VLPs. Purified fractions were diluted 1:25, applied to carbon coated grids and negatively stained with 2% uranyl acetate. FIG. 34A shows the purified chimera, blue arrows indicate examples of Chimeric VLPs (~55nm); FIG. 34B shows the purified HPV 16 LI positive control, orange arrows indicate examples of HPV16 LI VLPs of the appropriate size (~55nm); FIG. 34C shows the purified empty vector negative control. Red arrows indicate aggregated or misshapen particles.
[0069] FIG. 35 shows the schematic diagram of vaccination timeline.
[0070] FIG. 36 shows the analysis of sera antibodies by western and dot blot. Each lane contains HPV16 LI which was probed with the pooled mice sera from each group from each bleed. Lanes: + - positive control probed with CamVir, MW - Molecular weight marker (kDa), PB - Pre-bleed sera, B 1 - the initial bleed before the challenge, FB - Final bleed.
[0071] FIG. 37 shows the indirect ELISA of pooled mouse sera using plant produced HPV16 LI as coating antigen. Vaccine pre-bleeds and final bleeds absorbances at dilutions of 1:200. Titration curve of the mouse sera for the vaccine and control groups. The markers represent the average of the 3 repeats. Error bars represent the standard deviation.
[0072] FIGS. 38A and 38B show the protection of vaccines against HPV challenge. Images taken of the mice while in the IVIS machine (FIG. 38A). The average radiance for each mouse at each time point is plotted (FIG. 38B).
[0073] FIGS. 39A and 39B show the indirect ELISA of pooled mouse sera using biotinylated 2C7 peptide as coating antigen. Vaccine pre-bleed and final bleed absorbances at dilutions of 1 :1000 (FIG. 39A). Titration curve of the mouse sera for the vaccine and control groups (FIG. 39B). The bars represent the means of the triplicate readings. Error bars represent the standard deviation.
[0074] FIGS. 40A and 40B show the indirect ELISA of pooled mouse sera using LOS as coating antigen. Vaccine pre-bleed and final bleed absorbances at dilutions of 1:200 (FIG. 40A). Titration curve of the mouse sera for the vaccine and control groups (FIG. 40B). The bars represent the means of the triplicate readings. Error bars represent the standard deviation.
[0075] DETAILED DESCRIPTION
[0076] The following description of the disclosure is provided as an enabling teaching of the disclosure in its best, currently known embodiment(s). To this end, those skilled in the relevant art will recognize and appreciate that many changes can be made to the various embodiments of the invention described herein, while still obtaining the beneficial results of the present disclosure. It will also be apparent that some of the desired benefits of the present disclosure can be obtained by selecting some of the features of the present disclosure without utilizing other features. Accordingly, those who work in the art will recognize that many modifications and adaptations to the present disclosure are possible and can even be desirable in certain circumstances and are a part of the present disclosure. Thus, the following description is provided as illustrative of the principles of the present disclosure and not in limitation thereof.
[0077] Reference will now be made in detail to the embodiments of the invention, examples of which are illustrated in the drawings and the examples. This invention may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein.
[0078] Terminology
[0079] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood to one of ordinary skill in the art to which this disclosure belongs. The term “comprising” and variations thereof as used herein is used synonymously with the term “including” and variations thereof and are open, non-limiting terms. Although the terms “comprising” and “including” have been used herein to describe various embodiments, the terms “consisting essentially of’ and “consisting of’ can be used in place of “comprising” and “including” to provide for more specific embodiments and are also disclosed. As used in this disclosure and in the appended claims, the singular forms “a”, “an”, “the”, include plural referents unless the context clearly dictates otherwise.
[0080] The following definitions are provided for the full understanding of terms used in this specification.
[0081] The terms "about" and "approximately" are defined as being “close to” as understood by one of ordinary skill in the art. In one non-limiting embodiment the terms are defined to be within 10%. In another non-limiting embodiment, the terms are defined to be within 5%. In still another non-limiting embodiment, the terms are defined to be within 1%.
[0082] Ranges can be expressed herein as from “about” one particular value, and / or to “about” another particular value. When such a range is expressed, another embodiment includes from the one particular value and / or to the other particular value. Similarly, when values are expressed as approximations, by use of the antecedent “about,” it will be understood that the particular value forms another embodiment. It will be further understood that the endpoints of each of the ranges are significant both in relation to the other endpoint, and independently of the other endpoint. It is also understood that there are a number of values disclosed herein, and that each value is also herein disclosed as “about” that particular value in addition to the value itself. For example, if the value “10” is disclosed, then “about 10” is also disclosed. It is also understood that when a value is disclosed that “less than or equal to” the value, “greater than or equal to the value” and possible ranges between values are also disclosed, as appropriately understood by the skilled artisan. For example, if the value “10” is disclosed the “less than or equal to 10”as well as “greater than or equal to 10” is also disclosed. It is also understood that the throughout the application, data is provided in a number of different formats, and that this data represents endpoints and starting points, and ranges for any combination of the data points. For example, if a particular data point “10” and a particular data point 15 are disclosed, it is understood that greater than, greater than or equal to, less than, less than or equal to, and equal to 10 and 15 are considered disclosed as well as between 10 and 15. It is also understood that each unit between two particular units are also disclosed. For example, if 10 and 15 are disclosed, then 11, 12, 13, and 14 are also disclosed.
[0083] As used herein, the terms "may," "optionally," and "may optionally" are used interchangeably and are meant to include cases in which the condition occurs as well as cases in which the condition does not occur. Thus, for example, the statement that a formulation "may include an excipient" is meant to include cases in which the formulation includes an excipient as well as cases in which the formulation does not include an excipient.
[0084] "Comprising" is intended to mean that the compositions, methods, etc. include the recited elements, but do not exclude others. "Consisting essentially of" when used to define compositions and methods, shall mean including the recited elements, but excluding other elements of any essential significance to the combination. Thus, a composition consisting essentially of the elements as defined herein would not exclude trace contaminants from the isolation and purification method and pharmaceutically acceptable carriers, such as phosphate buffered saline, preservatives, and the like. "Consisting of' shall mean excluding more than trace elements of other ingredients and substantial method steps for administering the compositions provided and / or claimed in this disclosure. Embodiments defined by each of these transition terms are within the scope of this disclosure.
[0085] An "increase" can refer to any change that results in a greater amount of a symptom, disease, composition, condition, or activity. An increase can be any individual, median, or average increase in a condition, symptom, activity, composition in a statistically significant amount. Thus, the increase can be a 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, or 100% or more increase so long as the increase is statistically significant.
[0086] A "decrease" can refer to any change that results in a smaller amount of a symptom, disease, composition, condition, or activity. A substance is also understood to decrease the genetic output of a gene when the genetic output of the gene product with the substance is less relative to the output of the gene product without the substance. Also, for example, a decrease can be a change in the symptoms of a disorder such that the symptoms are less than previously observed. A decrease can be any individual, median, or average decrease in a condition, symptom, activity, composition in a statistically significant amount. Thus, the decrease can be a 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, or 100% decrease so long as the decrease is statistically significant.
[0087] "Inhibit," "inhibiting," and "inhibition" mean to decrease an activity, response, condition, disease, or other biological parameter. This can include but is not limited to the complete ablation of the activity, response, condition, or disease. This may also include, for example, a 10% reduction in the activity, response, condition, or disease as compared to the native or control level. Thus, the reduction can be a 10, 20, 30, 40, 50, 60, 70, 80, 90, 100%, or any amount of reduction in between as compared to native or control levels.
[0088] By “reduce” or other forms of the word, such as “reducing” or “reduction,” means lowering of an event or characteristic (e.g., bacterial and / or viral infections). It is understood that this is typically in relation to some standard or expected value, in other words it is relative, but that it is not always necessary for the standard or relative value to be referred to. For example, “reduces bacterial and / or viral infection” means reducing the rate of spread of a bacterial and / or viral pathogen in a host relative to a standard or a control.
[0089] By “prevent” or other forms of the word, such as “preventing” or “prevention,” means to stop a particular event or characteristic, to stabilize or delay the development or progression of a particular event or characteristic, or to minimize the chances that a particular event or characteristic will occur. Prevent does not require comparison to a control as it is typically more absolute than, for example, reduce. As used herein, something could be reduced but not prevented, but something that is reduced could also be prevented. Likewise, something could be prevented but not reduced, but something that is prevented could also be reduced. It is understood that where reduce or prevent are used, unless specifically indicated otherwise, the use of the other word is also expressly disclosed.
[0090] The term “subject” refers to any individual who is the target of administration or treatment. The subject can be a vertebrate, for example, a mammal. In one aspect, the subject can be human, non-human primate, bovine, equine, porcine, canine, or feline. The subject can also be a guinea pig, rat, hamster, rabbit, mouse, or mole. Thus, the subject can be a human or veterinary patient. The term “patient” refers to a subject under the treatment of a clinician, e.g., physician.
[0091] A “protein”, "polypeptide", or “peptide” each refer to a polymer of amino acids and does not imply a specific length of a polymer of amino acids. Thus, for example, the terms peptide, oligopeptide, protein, antibody, and enzyme are included within the definition of polypeptide.
[0092] The term “amino acid,” includes but is not limited to amino acids contained in the group consisting of alanine (Ala or A), cysteine (Cys or C), aspartic acid (Asp or D), glutamic acid (Glu or E), phenylalanine (Phe or F), glycine (Gly or G), histidine (His or H), isoleucine (I1e or I), lysine (Lys or K), leucine (Leu or L), methionine (Met or M), asparagine (Asn or N), proline (Pro or P), glutamine (Gin or Q), arginine (Arg or R), serine (Ser or S), threonine (Thr or T), valine (Vai or V), tryptophan (Trp or W), and tyrosine (Tyr or Y) residues. The term “amino acid residue” also may include amino acid residues contained in the group consisting of homocysteine, 2-Aminoadipic acid, N-Ethylasparagine, 3-Aminoadipic acid, Hydroxylysine, β-alanine, P-Amino-propionic acid, allo-Hydroxylysine acid, 2-Aminobutyric acid, 3 -Hydroxyproline, 4-Aminobutyric acid, 4-Hydroxyproline, piperidinic acid, 6- Aminocaproic acid, Isodesmosine, 2-Aminoheptanoic acid, allo-Isoleucine, 2- Aminoisobutyric acid, N-Methylglycine, sarcosine, 3 -Aminoisobutyric acid, N- Methylisoleucine, 2-Aminopimelic acid, 6-N-Methyllysine, 2,4-Diaminobutyric acid, N- Methylvaline, Desmosine, Norvaline, 2,2'-Diaminopimelic acid, Norleucine, 2,3- Diaminopropionic acid, Ornithine, and N-Ethylglycine.
[0093] Reference also is made herein to peptides, polypeptides, proteins, and compositions comprising peptides, polypeptides, and proteins. As used herein, a polypeptide and / or protein is defined as a polymer of amino acids, typically of length>100 amino acids (Garrett & Grisham, Biochemistry, 2nd edition, 1999, Brooks / Cole, 110). A peptide is defined as a short polymer of amino acids, of a length typically of 20 or less amino acids, and more typically of a length of 12 or less amino acids (Garrett & Grisham, Biochemistry, 2nd edition, 1999, Brooks / Cole, 110).
[0094] The phrases “percent identity” and “% identity,” as applied to polypeptide sequences, refer to the percentage of residue matches between at least two polypeptide sequences aligned using a standardized algorithm. Methods of polypeptide sequence alignment are well-known. Some alignment methods consider conservative amino acid substitutions. Such conservative substitutions, explained in more detail above, generally preserve the charge and hydrophobicity at the site of substitution, thus preserving the structure (and therefore function) of the polypeptide. Percent identity for amino acid sequences may be determined as understood in the art. (See, e.g., U.S. Pat. No. 7,396,664, which is incorporated herein by reference in its entirety). A suite of commonly used and freely available sequence comparison algorithms is provided by the National Center for Biotechnology Information (NCBI) Basic Local Alignment Search Tool (BLAST) (Altschul, S. F. et al. (1990) J. Mol. Biol. 215:403 410), which is available from several sources, including the NCBI, Bethesda, Md., at its website. The BLAST software suite includes various sequence analysis programs including “blastp,” that is used to align a known amino acid sequence with other amino acids sequences from a variety of databases.
[0095] Percent identity may be measured over the length of an entire defined polypeptide sequence or may be measured over a shorter length, for example, over the length of a fragment taken from a larger, defined polypeptide sequence, for instance, a fragment of at least 15, at least 20, at least 30, at least 40, at least 50, at least 70 or at least 150 contiguous residues. Such lengths are exemplary only, and it is understood that any fragment length may be used to describe a length over which percentage identity may be measured.
[0096] The present disclosure presents chimeric proteins, chimeric polypeptides, or compositions thereof. Fusion proteins and fusion polynucleotides are also contemplated herein. A “chimeric protein” or “fusion protein” refers to a protein formed by the fusion of at least one peptide, polypeptide, protein or variant thereof as disclosed herein to at least one molecule of a heterologous peptide, polypeptide, protein or variant thereof. The heterologous protein(s) may be fused at the N-terminus, the C-terminus, both termini, or internally. A fusion protein comprises at least a fragment or variant of the heterologous protein(s) that are fused with one another, preferably by genetic fusion (i.e., the fusion protein is generated by translation of a nucleic acid in which a polynucleotide encoding all or a portion of a first heterologous protein is joined in-frame with a polynucleotide encoding all or a portion of a second heterologous protein). The heterologous protein(s), once part of the fusion protein, may each be referred to herein as a “portion”, “region” or “moiety” of the fusion protein.
[0097] The terms “variant” or “derivative” mean a polypeptide derived from a parent protein by one or more (several) alteration(s), i.e., a substitution, insertion, and / or deletion, at one or more (several) positions, A substitution means a replacement of an amino acid occupying a position with a different amino acid; a deletion means removal of an amino acid occupying a position: and an insertion means adding 1 or more, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10, preferably 1-3 amino acids immediately adjacent an amino acid occupying a position, In relation to substitutions, 'immediately adjacent’ may be to the N-side ( / upstream’) or C-side (‘downstream’) of die amino acid occupying a position ('the named amino acid’). Therefore, for an amino acid named / numbered ‘X,’ the insertion may be at position ‘X+1 ' (‘downstream’) or at position ‘X-l’ ( ‘upstream’ ). A “variant,” “mutant,” or “derivative” of a particular polypeptide sequence may be defined as a polypeptide sequence having at least 50% sequence identity to the particular polypeptide sequence over a certain length of one of the polypeptide sequences using blastp with the “BLAST 2 Sequences” tool available at the National Center for Biotechnology Information's website. (See Tatiana A. Tatusova, Thomas L. Madden (1999), “Blast 2 sequences — a new tool for comparing protein and nucleotide sequences”, FEMS Microbiol Lett. 174:247-250). In some embodiments a variant polypeptide may show, for example, at least 60%, at least 70%, at least 80%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% or greater sequence identity over a certain defined length relative to a reference polypeptide.
[0098] A “variant,” “mutant,” or “derivative” polypeptide may have substantially the same functional activity as a reference polypeptide. For example, a variant polypeptide may exhibit one or more biological activities associated with binding a ligand and / or binding DNA at a specific binding site.
[0099] A “nucleotide” is a compound consisting of a nucleoside, which consists of a nitrogenous base and a 5-carbon sugar, linked to a phosphate group forming the basic structural unit of nucleic acids, such as DNA or RNA. The four types of DNA nucleotides are adenine (A), cytosine (C), guanine (G), and thymine (T), each of which are bound together by a phosphodiester bond to form a nucleic acid molecule.
[0100] A “nucleic acid” is a chemical compound that serves as the primary informationcarrying molecules in cells and make up the cellular genetic material. Nucleic acids comprise nucleotides, which are the monomers made of a 5-carbon sugar (usually ribose or deoxyribose), a phosphate group, and a nitrogenous base. A nucleic acid can also be a deoxyribonucleic acid (DNA) or a ribonucleic acid (RNA). A chimeric nucleic acid comprises two or more of the same kind of nucleic acid fused together to form one compound comprising genetic material.
[0101] The terms “percent identity” and “% identity,” as applied to polynucleotide sequences, refer to the percentage of residue matches between at least two polynucleotide sequences aligned using a standardized algorithm. Such an algorithm may insert, in a standardized and reproducible way, gaps in the sequences being compared in order to optimize alignment between two sequences, and therefore achieve a more meaningful comparison of the two sequences. Percent identity for a nucleic acid sequence may be determined as understood in the art. (See, e.g., U.S. Pat. No. 7,396,664, which is incorporated herein by reference in its entirety). A suite of commonly used and freely available sequence comparison algorithms is provided by the National Center for Biotechnology Information (NCBI) Basic Local Alignment Search Tool (BLAST) (Altschul, S. F. et al. (1990) J. Mol. Biol. 215:403 410), which is available from several sources, including the NCBI, Bethesda, Md., at its website. The BLAST software suite includes various sequence analysis programs including “blastn,” that is used to align a known polynucleotide sequence with other polynucleotide sequences from a variety of databases. Also available is a tool called “BLAST 2 Sequences” that is used for direct pairwise comparison of two nucleotide sequences. “BLAST 2 Sequences” can be accessed and used interactively at the NCBI website. The “BLAST 2 Sequences” tool can be used for both blastn and blastp (discussed above).
[0102] Percent identity may be measured over the length of an entire defined polynucleotide sequence or may be measured over a shorter length, for example, over the length of a fragment taken from a larger, defined sequence, for instance, a fragment of at least 20, at least 30, at least 40, at least 50, at least 70, at least 100, or at least 200 contiguous nucleotides. Such lengths are exemplary only, and it is understood that any fragment length may be used to describe a length over which percentage identity may be measured.
[0103] A “full length” polynucleotide sequence is one containing at least a translation initiation codon (e.g., methionine) followed by an open reading frame and a translation termination codon. A “full length” polynucleotide sequence encodes a “full length” polypeptide sequence.
[0104] A “ chimeric nucleic acid” or “fusion nucleic acid” refers to the fusion of the nucleotide sequence of a first polynucleotide to the nucleotide sequence of a second heterologous polynucleotide (e.g., the 3' end of a first polynucleotide to a 5' end of the second polynucleotide). Where the first and second polynucleotides encode proteins, the fusion may be such that the encoded proteins are in-frame and results in a chimeric protein or a fusion protein. The first and second polynucleotide may be fused such that the first and second polynucleotide are operably linked (e.g., as a promoter and a gene expressed by the promoter).
[0105] A “variant,” “mutant,” or “derivative” of a particular nucleic acid sequence may be defined as a nucleic acid sequence having at least 50% sequence identity to the particular nucleic acid sequence over a certain length of one of the nucleic acid sequences using blastn with the “BLAST 2 Sequences” tool available at the National Center for Biotechnology Information's website. (See Tatiana A. Tatusova, Thomas L. Madden (1999), “Blast 2 sequences — a new tool for comparing protein and nucleotide sequences”, FEMS Microbiol Lett. 174:247-250). In some embodiments a variant polynucleotide may show, for example, at least 60%, at least 70%, at least 80%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% or greater sequence identity over a certain defined length relative to a reference polynucleotide.
[0106] A “vector” refers to a DNA composition used as a vehicle to artificially carry foreign genetic material into another cell or tissue. A vector can be a plant vector, bacterial plasmid, a viral vector, or a nanoparticle.
[0107] The term “administer,” “administering”, or derivatives thereof refer to delivering a composition, substance, inhibitor, or medication to a subject or object by one or more the following routes: oral, topical, intravenous, subcutaneous, transcutaneous, transdermal, intramuscular, intra-joint, parenteral, intra-arteriole, intradermal, intraventricular, intracranial, intraperitoneal, intralesional, intranasal, rectal, vaginal, by inhalation or via an implanted reservoir. The term “parenteral” includes subcutaneous, intravenous, intramuscular, intraarticular, intra-synovial, intrasternal, intrathecal, intrahepatic, intralesional, and intracranial injections or infusion techniques.
[0108] A “vaccine” refers to a biological preparation that provides active acquired immunity to a particular infectious diseases caused by a virus, bacteria, parasite, or any other microorganisms. Vaccines typically comprise an agent or several agents, also referred to as antigens, resembling the disease-causing microorganism and is often made from weakened or killed forms of the microbe, its toxins, or its surface proteins / peptides. Vaccines are also made to comprise additional components, such as adjuvants, preservatives, and / or stabilizers to boost the immune response, improve safety, and improve vaccine storage.
[0109] "Pharmaceutically acceptable carrier" (sometimes referred to as a “carrier”) means a carrier or excipient that is useful in preparing a pharmaceutical or therapeutic composition, such as for example a vaccine) that is generally safe and non- toxic and includes a carrier that is acceptable for veterinary and / or human pharmaceutical or therapeutic use.
[0110] "Pharmaceutically acceptable" component can refer to a component that is not biologically or otherwise undesirable, i.e., the component may be incorporated into a pharmaceutical formulation of the disclosure and administered to a subject as described herein without causing significant undesirable biological effects or interacting in a deleterious manner with any of the other components of the formulation in which it is contained. When used in reference to administration to a human, the term generally implies the component has met the required standards of toxicological and manufacturing testing or that it is included on the Inactive Ingredient Guide prepared by the U.S. Food and Drug Administration. As used herein, the term “carrier” encompasses any excipient, diluent, filler, salt, buffer, stabilizer, solubilizer, lipid, stabilizer, or other material well known in the art for use in pharmaceutical formulations. The choice of a carrier for use in a composition will depend upon the intended route of administration for the composition. The preparation of pharmaceutically acceptable carriers and formulations containing these materials is described in, e.g., Remington's Pharmaceutical Sciences, 21st Edition, ed. University of the Sciences in Philadelphia, Lippincott, Williams & Wilkins, Philadelphia, PA, 2005. Examples of physiologically acceptable carriers include saline, glycerol, DMSO, buffers such as phosphate buffers, citrate buffer, and buffers with other organic acids; antioxidants including ascorbic acid; low molecular weight (less than about 10 residues) polypeptides; proteins, such as serum albumin, gelatin, or immunoglobulins; hydrophilic polymers such as polyvinylpyrrolidone; amino acids such as glycine, glutamine, asparagine, arginine or lysine; monosaccharides, disaccharides, and other carbohydrates including glucose, mannose, or dextrins; chelating agents such as EDTA; sugar alcohols such as mannitol or sorbitol; salt-forming counterions such as sodium; and / or nonionic surfactants such as TWEEN™ (ICI, Inc.; Bridgewater, New Jersey), polyethylene glycol (PEG), and PLURONICS™ (BASF; Florham Park, NJ). To provide for the administration of such dosages for the desired therapeutic treatment, compositions disclosed herein can advantageously comprise between about 0.1% and 99% by weight of the total of one or more of the subject compounds based on the weight of the total composition including carrier or diluent.
[0111] A “host” refers to any animal (either vertebrate or invertebrate) or plant that harbors a smaller organism; whether their relationship is parasitic, pathogenic, or symbiotic, where the smaller organism generally uses the animal or plant for shelter and / or nourishment. The smaller organism can be a microorganism, such as bacteria, viruses (including, but not limited to viruslike particles (VLPs), fungi, a parasite, including, but not limited to worms and insects.
[0112] A “virus-like particle” (VLP) refers to virus-derived structures made up of one or more different molecules with the ability to self-assemble, often mimicking the form and size of a virus, but often lacks the genetic material required for viral replication and infection.
[0113] “Serotype” as used herein refers to a distinct variation within a species of bacteria or virus or among immune cells of different individuals. These microorganisms, viruses, or cells are classified together based on their surface antigens, allowing the epidemiologic classification of organisms to the subspecies level. An “epitope” or “antigenic determinant” refer to the part of an antigen, a molecular structure, or foreign particulate that can bind to a specific antibody or T-cell receptor. The presence of antigens or epitopes of antigens within a host can illicit an immune response. A “mimitope” as used herein refers to a macromolecule, often a peptide, that mimics the structure of an epitope, or a targeted binding site on another protein.
[0114] As used herein, the term “infection” refers to the invasion of tissues by pathogens (such as, for example viruses and / or bacteria), their multiplication, and reaction of host tissues to the infectious agent and any toxins they release. Infections can be caused by a wide range of pathogen, most common are bacteria and viruses.
[0115] A “virus” is a microscopic infectious agent that replicates only inside the living cells of an organism. Viruses can infect all life forms, including mammalian and non-mammalian animals, plants, and other microorganisms. A complete virus, also known as a virion, consists of nucleic acid genetic material surrounded by a protective coat of protein called a capsid. Virus can have a lipid envelope derived from the infected host cell membrane. In general, there are five morphological virus types including helical, icosahedral, prolate, enveloped, and complex virus. A virus can either have a DNA or RNA genome, though a vast majority have RNA genomes. Irrespective of the type of nucleic acid genome, a viral genome can be either a singlestranded genome or a double-stranded genome.
[0116] A “bacteria” refers to a microorganism often consisting of one biological cell that display variety of sizes ranging from about 0.5 micrometers to about 5 micrometers. Many bacteria can infect numerous forms of life including, but not limited to mammalian and nonmammalian animals, plants, and other microorganisms. Many bacteria are spherical, called cocci (singular coccus), rod-shaped, called bacilli (singular bacillus), comma-shaped, called vibrio, or tightly coiled, called spirochaetes.
[0117] Chimeric VLPs and vaccine compositions
[0118] The present disclosure relates to chimeric compositions useful for developing and / or administering dual vaccines. As used herein, a “dual vaccine” refers to a vaccine comprising a combination of epitopes that target antigens from two or more different pathogens, such as for example different bacterial species, different viral species, or a combination of bacteria and viruses. The benefit of generating said compositions and / or vaccines includes, but are not limited to strengthening the antibody response of a host and / or accelerating vaccine development against troublesome or evasive pathogens, especially in resource-limited countries with vast spread of bacterial and / viral infections.
[0119] Human papillomavirus (HPV) is a small, non-enveloped, double- stranded DNA virus that is easily transmitted through skin-to-skin contact (also referred to as epi thelio tropic). HPV infections can originate from any one of a group of more than 200 related viruses causing no symptoms or more problematic symptoms, such as for example itching and warts. HPV infection often leads to development of genital lesions further contributing to approximately 95% of cervical cancer cases. Among HPV-infected individuals, concurrent infections have been linked including, but not limited to gonorrhea infections (originating from Neisseria gonorrhoeae (N. gonorrhoeae)). N. gonorrhoeae is a bacteria which causes approximately 87 million gonorrhea infections per year. The risk of cervical lesions progressing to cancer is increased with coinfection of N. gonorrhoeae and HPV. Due to the high prevalence of HPV and N. gonorrhoeae infections, there remains a need to develop preventative treatment to reduce pathogenic spread. In particular, development of a dual preventative treatment, such as a dual vaccine, would accelerate efforts to reduce spread of HPV and N. gonorrhoeae.
[0120] The present disclosure provides compositions comprising a chimeric polypeptide comprising an HPV polypeptide and a peptide mimic derived from N. gonorrhoeae . The present disclosure also provides methods using the chimeric polypeptide to induce immune responses and prevent infections from HPV, N. gonorrhoeae, or combinations thereof.
[0121] In one aspect, disclosed herein is a human papillomavirus (HPV) virus-like particle (VLP) comprising a chimeric polypeptide comprising an HPV polypeptide and a peptide mimic derived from Neisseria gonorrhoeae (N gonorrhoeae).
[0122] In one aspect, disclosed herein is a vaccine comprising a human papillomavirus (HPV) virus-like particle (VLP), wherein the HPV VLP comprises a chimeric polypeptide comprising the HPV polypeptide and the peptide mimic derived from Neisseria gonorrhoeae (N. gonorrhoeae) of any preceding aspect, and a pharmaceutically acceptable carrier selected from an excipient, a diluent, a salt, a buffer, a stabilizer, a lipid, or an emulsion.
[0123] Virus-like particles (VLPs) are molecules that mimic viruses, but are not infectious because they do not contain viral genetic material required for infections and replication. VLPs are considered effective vehicles to carry antigens to elicit immune responses. Once a host’s body initiates an immune response to the VLP, the host immune system will recognize the natural virus to prevent future infections. A VLP generally consists of one or more structural proteins that can be arranged in multiple layers with the outer most layer resembling at least virus. In some embodiments, the HPV VLP comprises structural HPV capsid proteins LI, L2, or a combination thereof.
[0124] The HPV VLP of the present disclosure is optimized by generating a chimeric polypeptide within the VLP. The chimeric polypeptide contains a N. gonorrhoeae peptide mimic inserted into an HPV polypeptide. Benefits of inserting the N. gonorrhoeae peptide mimic is to elicit an immune response against two pathogens during incidences of co-infection. Thus, once the host’s body initiates an immune response to the HPV VLP comprising the chimeric polypeptide, the host immune system will recognize both the HPV and N. gonorrhoeae to prevent future infections of one or both pathogens. It has been contemplated that combining N. gonorrhoeae and HPV antigens into a single vaccine provides more protection against N. gonorrhoeae and HPV relative to stand-alone vaccines to either N. gonorrhoeae or HPV.
[0125] In some embodiments, the chimeric polypeptide comprises at least 50% identity to SEQ ID NO: 2, or derivatives thereof. In some embodiments, the chimeric polypeptide comprises at least 60% identity to SEQ ID NO: 2, or derivatives thereof. In some embodiments, the chimeric polypeptide comprises at least 70% identity to SEQ ID NO: 2, or derivatives thereof. In some embodiments, the chimeric polypeptide comprises at least 75% identity to SEQ ID NO: 2, or derivatives thereof. In some embodiments, the chimeric polypeptide comprises at least 80% identity to SEQ ID NO: 2, or derivatives thereof. In some embodiments, the chimeric polypeptide comprises at least 85% identity to SEQ ID NO: 2, or derivatives thereof. In some embodiments, the chimeric polypeptide comprises at least 90% identity to SEQ ID NO: 2, or derivatives thereof. In some embodiments, the chimeric polypeptide comprises at least 95% identity to SEQ ID NO: 2, or derivatives thereof. In some embodiments, the chimeric polypeptide comprises at least 99% identity to SEQ ID NO: 2, or derivatives thereof. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 2, or derivatives thereof. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 2.
[0126] In some embodiments, the chimeric polypeptide is encoded by a nucleic acid sequence comprising at least 50% sequence identity to SEQ ID NO: 1, or derivatives thereof. In some embodiments, the chimeric polypeptide is encoded by a nucleic acid sequence comprising at least 60% sequence identity to SEQ ID NO: 1, or derivatives thereof. In some embodiments, the chimeric polypeptide is encoded by a nucleic acid sequence comprising at least 70% sequence identity to SEQ ID NO: 1, or derivatives thereof. In some embodiments, the chimeric polypeptide is encoded by a nucleic acid sequence comprising at least 75% sequence identity to SEQ ID NO: 1, or derivatives thereof. In some embodiments, the chimeric polypeptide is encoded by a nucleic acid sequence comprising at least 80% sequence identity to SEQ ID NO: 1, or derivatives thereof. In some embodiments, the chimeric polypeptide is encoded by a nucleic acid sequence comprising at least 85% sequence identity to SEQ ID NO: 1, or derivatives thereof. In some embodiments, the chimeric polypeptide is encoded by a nucleic acid sequence comprising at least 90% sequence identity to SEQ ID NO: 1, or derivatives thereof. In some embodiments, the chimeric polypeptide is encoded by a nucleic acid sequence comprising at least 95% sequence identity to SEQ ID NO: 1, or derivatives thereof. In some embodiments, the chimeric polypeptide is encoded by a nucleic acid sequence comprising at least 99% sequence identity to SEQ ID NO: 1, or derivatives thereof. In some embodiments, the chimeric polypeptide is encoded by a nucleic acid sequence comprising SEQ ID NO: 1, or derivatives thereof. In some embodiments, the chimeric polypeptide is encoded by a nucleic acid sequence comprising SEQ ID NO: 1.
[0127] In some embodiments, the chimeric polypeptide comprises at least 50% identity to SEQ ID NO: 10, or derivatives thereof. In some embodiments, the chimeric polypeptide comprises at least 60% identity to SEQ ID NO: 10, or derivatives thereof. In some embodiments, the chimeric polypeptide comprises at least 70% identity to SEQ ID NO: 10, or derivatives thereof. In some embodiments, the chimeric polypeptide comprises at least 75% identity to SEQ ID NO: 10, or derivatives thereof. In some embodiments, the chimeric polypeptide comprises at least 80% identity to SEQ ID NO: 10, or derivatives thereof. In some embodiments, the chimeric polypeptide comprises at least 85% identity to SEQ ID NO: 10, or derivatives thereof. In some embodiments, the chimeric polypeptide comprises at least 90% identity to SEQ ID NO: 10, or derivatives thereof. In some embodiments, the chimeric polypeptide comprises at least 95% identity to SEQ ID NO: 10, or derivatives thereof. In some embodiments, the chimeric polypeptide comprises at least 99% identity to SEQ ID NO: 10, or derivatives thereof. In some embodiments, the chimeric polypeptide comprises SEQ ID NO: 10, or derivatives thereof.
[0128] In some embodiments, the chimeric polypeptide is encoded by a nucleic acid sequence comprising at least 50% sequence identity to SEQ ID NO: 9, or derivatives thereof. In some embodiments, the chimeric polypeptide is encoded by a nucleic acid sequence comprising at least 60% sequence identity to SEQ ID NO: 9, or derivatives thereof. In some embodiments, the chimeric polypeptide is encoded by a nucleic acid sequence comprising at least 70% sequence identity to SEQ ID NO: 9, or derivatives thereof. In some embodiments, the chimeric polypeptide is encoded by a nucleic acid sequence comprising at least 75% sequence identity to SEQ ID NO: 9, or derivatives thereof. In some embodiments, the chimeric polypeptide is encoded by a nucleic acid sequence comprising at least 80% sequence identity to SEQ ID NO: 9, or derivatives thereof. In some embodiments, the chimeric polypeptide is encoded by a nucleic acid sequence comprising at least 85% sequence identity to SEQ ID NO: 9, or derivatives thereof. In some embodiments, the chimeric polypeptide is encoded by a nucleic acid sequence comprising at least 90% sequence identity to SEQ ID NO: 9, or derivatives thereof. In some embodiments, the chimeric polypeptide is encoded by a nucleic acid sequence comprising at least 95% sequence identity to SEQ ID NO: 9, or derivatives thereof. In some embodiments, the chimeric polypeptide is encoded by a nucleic acid sequence comprising at least 99% sequence identity to SEQ ID NO: 9, or derivatives thereof. In some embodiments, the chimeric polypeptide is encoded by a nucleic acid sequence comprising SEQ ID NO: 9, or derivatives thereof.
[0129] In some embodiments, the peptide mimic comprises a 2C7 peptide.
[0130] In some embodiments, the peptide mimic comprises at least 70% sequence identity to SEQ ID NO: 21, SEQ ID NO: 23, or derivatives thereof. In some embodiments, the peptide mimic comprises at least 75% sequence identity to SEQ ID NO: 21, SEQ ID NO: 23, or derivatives thereof. In some embodiments, the peptide mimic comprises at least 80% sequence identity to SEQ ID NO: 21, SEQ ID NO: 23, or derivatives thereof. In some embodiments, the peptide mimic comprises at least 85% sequence identity to SEQ ID NO: 21, SEQ ID NO: 23, or derivatives thereof. In some embodiments, the peptide mimic comprises at least 90% sequence identity to SEQ ID NO: 21, SEQ ID NO: 23, or derivatives thereof. In some embodiments, the peptide mimic comprises at least 95% sequence identity to SEQ ID NO: 21, SEQ ID NO: 23, or derivatives thereof. In some embodiments, the peptide mimic comprises at least 99% sequence identity to SEQ ID NO: 21, SEQ ID NO: 23, or derivatives thereof. In some embodiments, the peptide mimic comprises SEQ ID NO: 21, SEQ ID NO: 23, or derivatives thereof.
[0131] In some embodiments, the peptide mimic comprises at least 70% (for example, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 99%) sequence identity to SEQ ID NO: 21. In some embodiments, the peptide mimic comprises SEQ ID NO: 21.
[0132] In some embodiments, the peptide mimic comprises at least 70% (for example, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 99%) sequence identity to SEQ ID NO: 23. In some embodiments, the peptide mimic comprises SEQ ID NO: 23.
[0133] In some embodiments, the peptide mimic is encoded by a nucleic acid sequence comprising at least 70% sequence identity to SEQ ID NO: 22, SEQ ID NO: 24, or derivatives thereof. In some embodiments, the peptide mimic is encoded by a nucleic acid sequence comprising at least 75% sequence identity to SEQ ID NO: 22, SEQ ID NO: 24, or derivatives thereof. In some embodiments, the peptide mimic is encoded by a nucleic acid sequence comprising at least 80% sequence identity to SEQ ID NO: 22, SEQ ID NO: 24, or derivatives thereof. In some embodiments, the peptide mimic is encoded by a nucleic acid sequence comprising at least 85% sequence identity to SEQ ID NO: 22, SEQ ID NO: 24, or derivatives thereof. In some embodiments, the peptide mimic is encoded by a nucleic acid sequence comprising at least 90% sequence identity to SEQ ID NO: 22, SEQ ID NO: 24, or derivatives thereof. In some embodiments, the peptide mimic is encoded by a nucleic acid sequence comprising at least 95% sequence identity to SEQ ID NO: 22, SEQ ID NO: 24, or derivatives thereof. In some embodiments, the peptide mimic is encoded by a nucleic acid sequence comprising at least 99% sequence identity to SEQ ID NO: 22, SEQ ID NO: 24, or derivatives thereof. In some embodiments, the peptide mimic is encoded by a nucleic acid sequence comprising SEQ ID NO: 22, SEQ ID NO: 24, or derivatives thereof. In some embodiments, the peptide mimic comprises an epitope. It should be understood that the terms “epitope” and “mimitope” can be used interchangeably throughout the disclosure.
[0134] In some embodiments, the peptide mimic is encoded by a nucleic acid sequence comprising at least 70% (for example, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 99%) sequence identity to SEQ ID NO: 22. In some embodiments, the peptide mimic is encoded by SEQ ID NO: 22.
[0135] In some embodiments, the peptide mimic is encoded by a nucleic acid sequence comprising at least 70% (for example, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 99%) sequence identity to SEQ ID NO: 24. In some embodiments, the peptide mimic is encoded by SEQ ID NO: 24.
[0136] In some embodiments, the peptide mimic comprises a multi-antigen peptide, such as for example a tetrapeptide. A “tetrapeptide” refers to an oligopeptide comprising four amino acid sequences; A, B, C, and / or D joined together by a peptide bond, wherein A, B, C, and / or D each represent a different amino acid sequence. It should be understood that the amino acid sequences A, B, C, and / or D can be arranged in any order within the tetrapeptide. Also, any one amino acid sequence selected A, B, C, and / or D can be excluded from the tetrapeptide and another amino acid sequence can be repeated in the tetrapeptide.
[0137] In some embodiments, the peptide mimic comprises a multimer peptide. A “multimer peptide” refers to an oligopeptide comprising a nonlimiting number of amino acid sequences joined together by a peptide bond, wherein the nonlimiting number is greater than one.
[0138] In some embodiments, the HPV polypeptide comprises at least 50% sequence identity to SEQ ID NO: 20, or derivatives thereof. In some embodiments, the HPV polypeptide comprises at least 60% sequence identity to SEQ ID NO: 20, or derivatives thereof. In some embodiments, the HPV polypeptide comprises at least 70% sequence identity to SEQ ID NO: 20, or derivatives thereof. In some embodiments, the HPV polypeptide comprises at least 75% sequence identity to SEQ ID NO: 20, or derivatives thereof. In some embodiments, the HPV polypeptide comprises at least 80% sequence identity to SEQ ID NO: 20, or derivatives thereof. In some embodiments, the HPV polypeptide comprises at least 85% sequence identity to SEQ ID NO: 20, or derivatives thereof. In some embodiments, the HPV polypeptide comprises at least 90% sequence identity to SEQ ID NO: 20, or derivatives thereof. In some embodiments, the HPV polypeptide comprises at least 95% sequence identity to SEQ ID NO: 20, or derivatives thereof. In some embodiments, the HPV polypeptide comprises at least 99% sequence identity to SEQ ID NO: 20, or derivatives thereof. In some embodiments, the HPV polypeptide comprises SEQ ID NO: 20, or derivatives thereof.
[0139] In some embodiments, the HPV polypeptide is encoded by a nucleic acid comprising at least 50% sequence identity to SEQ ID NO: 19, or derivatives thereof. In some embodiments, the HPV polypeptide is encoded by a nucleic acid comprising at least 60% sequence identity to SEQ ID NO: 19, or derivatives thereof. In some embodiments, the HPV polypeptide is encoded by a nucleic acid comprising at least 70% sequence identity to SEQ ID NO: 19, or derivatives thereof. In some embodiments, the HPV polypeptide is encoded by a nucleic acid comprising at least 75% sequence identity to SEQ ID NO: 19, or derivatives thereof. In some embodiments, the HPV polypeptide is encoded by a nucleic acid comprising at least 80% sequence identity to SEQ ID NO: 19, or derivatives thereof. In some embodiments, the HPV polypeptide is encoded by a nucleic acid comprising at least 85% sequence identity to SEQ ID NO: 19, or derivatives thereof. In some embodiments, the HPV polypeptide is encoded by a nucleic acid comprising at least 90% sequence identity to SEQ ID NO: 19, or derivatives thereof. In some embodiments, the HPV polypeptide is encoded by a nucleic acid comprising at least 95% sequence identity to SEQ ID NO: 19, or derivatives thereof. In some embodiments, the HPV polypeptide is encoded by a nucleic acid comprising at least 99% sequence identity to SEQ ID NO: 19, or derivatives thereof. In some embodiments, the HPV polypeptide is encoded by a nucleic acid comprising SEQ ID NO: 19, or derivatives thereof.
[0140] In some embodiments, the HPV polypeptide is derived from an HPV 16 virus. In some embodiments, the HPV polypeptide is derived from an HPV 18 virus. In some embodiments, the HPV polypeptide is derived from a high-risk HPV serotype. In some embodiments, the HPV polypeptide is derived from a low-risk HPV serotype. In some embodiments, the HPV polypeptide is derived from any HPV serotype selected from 6, 11, 42, 43, 44, 31, 33, 34, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68, or 70.
[0141] In some embodiments, the peptide mimic is inserted into the HPV polypeptide. In some embodiments, the peptide mimic is inserted into an LI capsid peptide. In some embodiments, the LI capsid peptide comprises a DE loop. In some embodiments, the LI capsid peptide comprises a h4 helix.
[0142] The LI capsid peptide of HPV16 is about a 55kDa peptide (-505 amino acids) that allows the HPV the ability to spontaneously self-assemble into VLPs. In some embodiments, the peptide mimic is inserted between amino acids 131 and 132 of the DE loop. In some embodiments, the peptide mimic is inserted between any two amino acids of the LI capsid (between amino acids 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22,
[0143] 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47,
[0144] 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72,
[0145] 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97,
[0146] 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135,
[0147] 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154,
[0148] 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173,
[0149] 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192,
[0150] 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211,
[0151] 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230,
[0152] 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249,
[0153] 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268,
[0154] 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283, 284, 285, 286, 287,
[0155] 288, 289, 290, 291, 292, 293, 294, 295, 296, 297, 298, 299, 300, 301, 302, 303, 304, 305, 306,
[0156] 307, 308, 309, 310, 311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322, 323, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335, 336, 337, 338, 339, 340, 341, 342, 343, 344,
[0157] 345, 346, 347, 348, 349, 350, 351, 352, 353, 354, 355, 356, 357, 358, 359, 360, 361, 362, 363,
[0158] 364, 365, 366, 367, 368, 369, 370, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380, 381, 382,
[0159] 383, 384, 385, 386, 387, 388, 389, 390, 391, 392, 393, 394, 395, 396, 397, 398, 399, 400, 401,
[0160] 402, 403, 404, 405, 406, 407, 408, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420,
[0161] 421, 422, 423, 424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 436, 437, 438, 439,
[0162] 440, 441, 442, 443, 444, 445, 446, 447, 448, 449, 450, 451, 452, 453, 454, 455, 456, 457, 458,
[0163] 459, 460, 461, 462, 463, 464, 465, 466, 467, 468, 469, 470, 471, 472, 473, 474, 475, 476, 477,
[0164] 478, 479, 480, 481, 482, 483, 484, 485, 486, 487, 488, 489, 490, 491, 492, 493, 494, 495, 496,
[0165] 497, 498, 499, 500, 501, 502, 503, 504, or 505).
[0166] Methods of preventing infections and / or inducing an immune response
[0167] In one aspect, disclosed herein is a method of inducing an immune response to a human papillomavirus (HPV), Neisseria gonorrhoeae (N. gonorrhoeae), or combinations thereof, the method comprising administering to a subject an HPV virus-like particle (VLP) composition, including, but not limited to a vaccine comprising the chimeric polypeptide of any preceding aspect and a pharmaceutically acceptable carrier selected from an excipient, a diluent, a salt, a buffer, a stabilizer, a lipid, or an emulsion.
[0168] In one aspect, disclosed herein is a method of preventing an infection from a human papillomavirus (HPV), Neisseria gonorrhoeae (N. gonorrhoeae), or combinations thereof, the method comprising administering to a subject a vaccine comprising an HPV virus-like particle (VLP) comprising chimeric polypeptide of any preceding aspect and a pharmaceutically acceptable carrier selected from an excipient, a diluent, a salt, a buffer, a stabilizer, a lipid, or an emulsion.
[0169] In some embodiments, the method induces an immune response against an V. gonorrhoeae bacterium, a human papillomavirus, or combination thereof. In some embodiments, the immune response comprises an antibody response against an V. gonorrhoeae bacterium, a human papillomavirus, or combination thereof. In some embodiments, the immune response comprises clearance of the N. gonorrhoeae bacterium, the human papillomavirus, or combination thereof.
[0170] In some embodiments, the peptide mimic elicits one or more bactericidal antibodies and / or accelerates clearance of N. gonorrhoeae bacterium from a host. In some embodiments, the method comprises administering to a subject a vaccine comprising an HPV virus-like particle (VLP) comprising chimeric polypeptide of any preceding aspect and a pharmaceutically acceptable carrier selected from an excipient, a diluent, a salt, a buffer, a stabilizer, a lipid, or an emulsion. The vaccine may be administered in such amounts, time, and route deemed necessary in order to achieve the desired result. The exact amount of the vaccine will vary from subject to subject, depending on the species, age, and general condition of the subject, the severity of the infection(s), the particular vaccine composition, its mode of administration, its mode of activity, and the like. The vaccine is preferably formulated in dosage unit form for ease of administration and uniformity of dosage. It will be understood, however, that the total usage of the vaccine will be decided by the attending physician within the scope of sound medical judgment. The specific therapeutically effective dose level for any particular subject will depend upon a variety of factors including the infection being treated and the severity of the disease; the activity of the vaccine composition employed; the specific vaccine composition employed; the age, body weight, general health, sex and diet of the patient; the time of administration, route of administration, and rate of excretion of the specific vaccine composition employed; the duration of the treatment; drugs used in combination or coincidental with the specific vaccine composition employed; and like factors well known in the medical arts.
[0171] The vaccine composition may be administered by any route. In some embodiments, the vaccine composition is administered via a variety of routes, including intravenous, intramuscular, subcutaneous, transdermal, interdermal, intraperitoneal, and / or as a nasal spray, and / or aerosol. In general, the most appropriate route of administration will depend upon a variety of factors including the nature of the vaccine composition (e.g., its stability in the environment of the host’s body), the condition of the subject (e.g., whether the subject is able to tolerate administration), etc.
[0172] The exact amount of vaccine composition required to achieve a therapeutically or prophylactically effective amount will vary from subject to subject, depending on species, age, and general condition of a subject, severity of the side effects, identity of the particular compound(s), mode of administration, and the like. The amount to be administered to, for example, a child or an adolescent can be determined by a medical practitioner or person skilled in the art and can be lower or the same as that administered to an adult.
[0173] In one aspect, disclosed herein is an HPV virus-like particle (VLP) comprising chimeric polypeptide of any preceding aspect and a pharmaceutically acceptable carrier selected from an excipient, a diluent, a salt, a buffer, a stabilizer, a lipid, and an emulsion. One or more active agents (e.g. HPV VLP comprising the chimeric polypeptide) can be administered in the “native” form or, if desired in the form of salts, esters, amides, prodrugs, or a derivative that is pharmacologically suitable. Salts, esters, amides, prodrugs, and other derivatives of the active agents can be prepared using standards procedures known to those skilled in the art of synthetic organic chemistry and described, for example, by March (1992) Advanced Organic Chemistry; Reactions, Mechanisms, and Structure, 4* Ed. N.Y. Wiley-Interscience.
[0174] In some embodiments, the vaccine composition can be prepared as a “concentrate”, e.g. in a storage container of a premeasure volume and / or a predetermined amount ready for dilution.
[0175] In some embodiments, the vaccine composition of any preceding aspect is administered 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28,
[0176] 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,
[0177] 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78,
[0178] 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, or more times. In some embodiments, the vaccine composition is administered daily. In some embodiments, the vaccine composition is administered every day, every 2 days, every 3 days, every 4 days, every 5 days, every 6 days, every 7 days, or more. In some embodiments, the vaccine composition is administered every week, every 2 weeks, every 3 weeks, every 4 weeks, or more. In some embodiments, the vaccine composition is administered every month, every 2 months, every 3 months, every 4 months, every 5 months, every 6 months, every 7 months, every 8 months, every 9 months, every 10 months, every 11 months, every 12 months, or more. In some embodiments, the vaccine composition is administered every year, every 2 years, every 3 years, every 4 years, every 5 years, or more.
[0179] Methods of producing, generating, and / or creating a chimeric VLP
[0180] The present disclosure describes plant molecular farming to generate pharmaceutical compositions. As used herein, “plant molecular farming” refers to the process of producing, generating, creating, and / or developing pharmaceutical compositions, such as for example vaccines, in plant hosts. Plant host are attractive platforms for the production of high value pharmaceuticals compared to bacterial and mammalian systems because plant hosts are cost effective, have highly scalable production, fewer safety concerns, and can gamer the ability to assemble complex multi-subunit compositions, such as multimeric polypeptides. In one aspect, disclosed herein is a method of producing the HPV VLP of any preceding aspect, the method comprising generating a chimeric nucleic acid sequence by inserting a first nucleic acid sequence encoding the peptide mimic into a second nucleic acid sequence encoding the HPV polypeptide, transferring the chimeric nucleic acid sequence into a binary expression vector, infiltrating the binary expression vector of step b) into a tobacco plant by Agrobacterium-mediated transient expression (agroinfiltration), expressing the HPV VLP in the tobacco plant, wherein the HPV VLP comprises a chimeric polypeptide, and purifying the HPV VLP from the tobacco plant.
[0181] In some embodiments, the peptide mimic is inserted between any two amino acids from 1-505 amino acids of the LI capsid. In some embodiments, the peptide mimic is inserted between amino acids 131 and 132 of the DE loop within the LI capsid.
[0182] In some embodiments, the chimeric polypeptide comprises an HPV polypeptide and a peptide mimic derived from N. gonorrhoeae. In some embodiments, the first nucleic acid sequence comprises SEQ ID NO: 22 SEQ ID NO: 24, or derivatives thereof. In some embodiments, the second nucleic acid sequence comprises SEQ ID NO: 19, or derivatives thereof.
[0183] In some embodiments, the plant expression vector comprises at least 70% sequence identity to SEQ ID NO: 17, SEQ ID NO: 18, or derivatives thereof. In some embodiments, the plant expression vector comprises at least 75% sequence identity to SEQ ID NO: 17, SEQ ID NO: 18, or derivatives thereof. In some embodiments, the plant expression vector comprises at least 80% sequence identity to SEQ ID NO: 17, SEQ ID NO: 18, or derivatives thereof. In some embodiments, the plant expression vector comprises at least 85% sequence identity to SEQ ID NO: 17, SEQ ID NO: 18, or derivatives thereof. In some embodiments, the plant expression vector comprises at least 90% sequence identity to SEQ ID NO: 17, SEQ ID NO: 18, or derivatives thereof. In some embodiments, the plant expression vector comprises at least 95% sequence identity to SEQ ID NO: 17, SEQ ID NO: 18, or derivatives thereof. In some embodiments, the plant expression vector comprises at least 99% sequence identity to SEQ ID NO: 17, SEQ ID NO: 18, or derivatives thereof. In some embodiments, the plant expression vector comprises SEQ ID NO: 17, SEQ ID NO: 18, or derivatives thereof. In some embodiments, the plant expression vector comprises a bacterial plasmid. In some embodiments, the plant expression vector comprises a pTRAkc-rbcsl-cTP vector or a pRIC3 vector. In some embodiments, the plant expression vector comprises a chloroplast- specific targeting sequence. In some embodiments, the plant expression vector comprises a geminivirus-based self-replicating viral vector.
[0184] In some embodiments, the method comprises a plant-specific plasmid. In some embodiments, the plant expression vector comprises a plant-specific viral vector.
[0185] Like mammalian and bacterial genetics, plants comprise genetic material in the form of DNA and RNA that is located in the plant nuclei, mitochondria, and chloroplast. A “chloroplast” refers to a plant-specific membrane-bound organelle (also known as a plastid) that contains its own genome and conducts photosynthesis to capture and store energy. The agrobacterium-mediated gene transfer is a stable transformation process to introduce exogenous genetic material into the nuclear or chloroplast genomes of a plant host. It has been demonstrated that transformation of genetic material into chloroplasts allows for higher expression levels of target proteins relative to transformation into the nucleus (Loh et al. “Using transgenic plants and modified plant viruses for the development of treatments for human diseases” (2017)). The agroinfiltration method uses a suspension of Agrobacterium tumefaciens (A. tumefaciens^ comprising a plant expression vector to infiltrate, or enter into, a plant cell. Examples of agrobacterium-mediated methods can be found in Talakar (2017) and Loh (2017), herein incorporated by reference in their entirety, for teachings concerning agroinfiltration, transgenic plants, and methods of expressing pharmaceutical compositions from plant hosts.
[0186] In some embodiments, the plant expression vector is infiltrated into the tobacco plant using an Agrobacterium -mediated gene transfer method. In some embodiments, the chimeric HPV VLP is purified by ultracentrifugation through an iodixanol density gradient. In some embodiments, the tobacco plant comprises Nicotiana benthamiana (N. benthamiana). An example of N. benthamiana as a plant model can be found in Bally et al (2018), herein incorporated by reference in its entirety, for teachings concerning N. benthamiana as a plant host for expressing target proteins in agroinfiltration. In some embodiments, the method comprises a 2C7 peptide mimic.
[0187] In some embodiments, the method comprises the HPV polypeptide derived from an HPV 16 virus. In some embodiments, the method comprises the HPV polypeptide derived from an HPV 18 virus. In some embodiments, the method comprises the HPV polypeptide derived from a high-risk HPV serotype. In some embodiments, the method comprises the HPV polypeptide derived from a low-risk HPV serotype. In some embodiments, the method comprises the HPV polypeptide derived from any HPV serotype selected from 6, 11, 42, 43, 44, 31, 33, 34, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68, or 70.
[0188] Plant expression vectors
[0189] Plant expression vectors have been designed to facilitate the generation of transgenic plants. Plant expression vectors can also be referred to as plant transformation vectors that are plasmids with the ability to replicate in bacterium, such as for example Agrobacterium tumefaciens.
[0190] In one aspect, disclosed herein is a plant expression vector comprising a nucleic acid sequence encoding a chimeric polypeptide comprising an HPV polypeptide and a peptide mimic derived from N. gonorrhoeae, wherein the plant expression vector comprises at least 70% identity to SEQ ID NO: 25, SEQ ID NO: 29, or derivatives thereof.
[0191] In some embodiments, the plant expression vector comprises a plasmid. In some embodiments, the plant expression vector comprises a viral vector.
[0192] In some embodiments, the plant expression vector comprises one or more components required for replication in a bacterium and stable infiltration into a plant host. In some embodiments, the plant expression vector comprises at least one selection gene selected from kanamycin, ampicillin, spectinomycin, tetracycline, or combinations thereof. In some embodiments, the plant expression vector comprises at least one origin of replication, or the position within the plant expression vector where DNA replication is initiated. In some embodiments, the plant expression vector comprises at least one T-DNA region. As used herein, a “T-DNA region” refers to two types of genes: oncogenic genes encoding enzymes involved in the synthesis of auxins and cytokinins, and are responsible for tumor formation; and genes encoding the synthesis of opines, which are a source of nutrition for bacteria, specifically A. tumefaciens.
[0193] In some embodiments, the plant expression vector and the nucleic acid sequence comprise at least 75% identity to SEQ ID NO: 25, SEQ ID NO: 29, or derivatives thereof. In some embodiments, the plant expression vector and the nucleic acid sequence comprise at least 80% identity to SEQ ID NO: 25, SEQ ID NO: 29, or derivatives thereof. In some embodiments, the plant expression vector and the nucleic acid sequence comprise at least 85% identity to SEQ ID NO: 25, SEQ ID NO: 29, or derivatives thereof. In some embodiments, the plant expression vector and the nucleic acid sequence comprise at least 90% identity to SEQ ID NO: 25, SEQ ID NO: 29, or derivatives thereof. In some embodiments, the plant expression vector and the nucleic acid sequence comprise at least 95% identity to SEQ ID NO: 25, SEQ ID NO: 29, or derivatives thereof. In some embodiments, the plant expression vector and the nucleic acid sequence comprise at least 99% identity to SEQ ID NO: 25, SEQ ID NO: 29, or derivatives thereof. In some embodiments, the plant expression vector and the nucleic acid sequence comprise SEQ ID NO: 25, SEQ ID NO: 29, or derivatives thereof.
[0194] In some embodiments, the nucleic acid sequence comprises SEQ ID NO: 22, SEQ ID NO: 24, or derivatives thereof, inserted into SEQ ID NO: 19, or derivatives thereof. In some embodiments, the plant expression vector comprises a pTRAkc-rbcsl-cTP vector or a pRIC3 vector. In some embodiments, the plant expression vector comprises a chloroplast-specific targeting sequence. In some embodiments, the plant expression vector comprises a geminivirus-based self-replicating viral vector.
[0195] A number of embodiments of the disclosure have been described. Nevertheless, it will be understood that various modifications may be made without departing from the spirit and scope of the invention. Accordingly, other embodiments are within the scope of the following claims.
[0196] By way of non-limiting illustration, examples of certain embodiments of the present disclosure are given below.
[0197] EXAMPLES
[0198] The following examples are set forth below to illustrate the compositions, devices, methods, and results according to the disclosed subject matter. These examples are not intended to be inclusive of all aspects of the subject matter disclosed herein, but rather to illustrate representative methods and results. These examples are not intended to exclude equivalents and variations of the present invention which are apparent to one skilled in the art.
[0199] Example 1: Gonococcal peptide vaccines display using HPV virus-like particles (VLPs)
[0200] By making use of HPV VLPs, a 2C7 epitope can be displayed in the DE loop of the VLPs which can then be delivered to create a dual vaccination for both HPV- 16 as well as Gonorrhea. Plant culturing is scalable, has a short production time, has a low risk of contamination, and is cost effective. For these reasons, plant culturing poses as a production method for novel vaccinations. Herein, chimeric HPV-A'g VLPs are produced in plants and their immunogenicity tested in a mouse challenge model. This is achieved using Agroinfiltration of Nicotiana benthamiana (N. benthamiana) as the expression system. Followed by purification of the VLPs by gradient densitometry. The VLPs are used for the vaccination of BALB / c mice which is then used in a challenge model with mammalian produced HPV 16 Pseudo Viruses (PsVs) to test for protection against HPV 16. Currently generation I and generation II chimeras have been developed with and without flanking Cys residues respectively. The generation I chimera with the 2C7 is inserted into the DE loop of the LI protein produce the highest quality plant produced VLPs shown by examination using transmission electron microscopy. The vaccination of BALB / c mice show that they become effectively immunized against both HPV 16 as well as Gonorrhea.
[0201] Example 2: The production of a plant-based chimeric vaccine against HPV and gonorrhea
[0202] Neisseria gonorrhoeae (Ng) is a bacteria which causes approximately 87 million gonorrhea infections globally per year. Cervical cancer is the fourth most prevalent cancer in women globally, with an estimated 604 000 reported cases in 2020. Approximately 95% of cervical cancer cases are a result of human papillomavirus (HPV) infections. The HPV major capsid protein: LI can self-assemble into highly immunogenic virus-like particles (VLPs) that structurally mimic native virions and has already proven to be an effective vaccine. By making use of HPV VLPs, a peptide mimic of the Ng lipooligosaccharide (LOS) epitope recognized by mAb 2C7 (called the 2C7 epitope) was displayed in the DE loop of LI which still permitted VLP formation, thereby creating a dual vaccine (HPV-Ng) against both HPV-16 and gonorrhea.
[0203] Transmission electron microscopy (TEM) confirmed that the transiently expressed HPV- Ng chimaera successfully assembled into VLPs that resembled native HPV virions. Immune sera from mice vaccinated with chimeric VLPs showed that the vaccine elicited an immune response against both HPV and Ng by western blot and ELISA analysis. Vaccinated mice were protected against challenge with mammalian cell-produced HPV pseudovirions.
[0204] This disclosure shows that plant-based expression provides a platform for the production of dual vaccine against HPV and gonorrhea. Example 3: Expression and purification of HPV-Ng chimeric virus-like particles (VLPs) in Nicotiana benthamiana (N. benthamiana)
[0205] Constructs
[0206] Several studies have shown that insertion or substitution of several peptides (HPV and non-HPV related) into various HPV LI surface loops does not affect chimeric VLP (cVLP) assembly (Matic et al., 2011; Sadeyen et al., 2003; Slupetzky et al., 2001; Varsani et al., 2003). The Ng 2C7 mimitope was introduced into the HPV LI gene to create two iterations (Figure 1).
[0207] Generation I (gen I)
[0208] The 2C7 mimitope: Cys-Gly-Pro-Ile-Pro-Val-Leu-Asp-Glu-Asn-Gly-Leu-Phe-Ala- Pro-Gly-Pro-Cys (SEQ ID NO: 21) was inserted or substituted into the HPV-16 LI gene at 2 positions: the DE loop or h4 helix.
[0209] • Insertion at position 131 / 132 (DE_i) or position 414 / 415 (h4_i)
[0210] • Substitution from position 131 (DE_s) or from position 414 (h4_s)
[0211] Generation II (gen II)
[0212] The 2C7 mimitope only (without flanking residues): Ile-Pro-Val-Leu-Asp-Glu-Asn- Gly-Leu-Phe-Ala- Pro (SEQ ID NO: 23) was inserted or substituted into the HPV-16 LI gene at 2 positions: the DE loop or h4 helix.
[0213] • Insertion at position 131 / 132 (DE_i) or position 414 / 415 (h4_i)
[0214] • Substitution from position 131 (DE_s) or from position 414 (h4_s)
[0215] Gen I and gen II constructs were synthesized by Genscript and subcloned into two plant expression vectors:
[0216] • pTRAkc-rbcsl-cTP (CTP), a chloroplast targeting expression vector
[0217] • pRIC3 - a geminivirus-based self-replicating viral vector.
[0218] All clones were confirmed by colony PCR and sequencing.
[0219] Expression of HPV-Ng recombinant clones
[0220] Recombinant clones were transformed into Agrobacterium tumefaciens. N. benthamiana plants (5-6 weeks old) were infiltrated with recombinant Agrobacterium suspensions by syringe infiltration (small-scale) or by applying a vacuum (100 kPa) (large- scale) and grown for 4 or 5 days at 22°C under 16 h / 8 h light / dark cycle. Generation I
[0221] Small-scale expression 1
[0222] All gen I clones (except pRIC3 LL2C7 h4_i*) were initially infiltrated at small-scale (2 leaves per construct; recombinant Agrobacterium tumefaciens culture at OD600 0.25). Plants infiltrated with pRIC3 constructs displayed more chlorosis and necrosis than CTP constructs (Figure 2).
[0223] Western blots to detect LI and 2C7 protein from crude extracts were performed (Figure 3). Only CTP LL2C7 h4_i and pRIC3 LL2C7 h4_s showed the correct LI band (56 kDa), detected using anti-Ll mAb Camvir-1 (Abeam) (Figure 3A). Detection of the 2C7 peptide with anti-2C7 mAb was unclear as although there is a band (which only appeared after overnight development). At this time, it is suspected that the 2C7 epitope has not been correctly displayed.
[0224] Based on these results and despite the fact that these were crude preparations, VLP formation was assessed via electron microscopy (EM). From the LI western blot results, CTP LL2C7 h4_i were observed. VLPs of 40-55 nm were observed for CTP LL2C7 h4_i, with the background showing capsomeres -10 nm (Figure 4).
[0225] Large-scale expression 1
[0226] To improve visualization of VLPs, expression of CTP LI :2C7 h4_i and pRIC3 LI :2C7 h4_s was scaled up and 30g of leaf material extracted and purified by density gradient ultracentrifugation. Western blots to detect LI and 2C7 protein in purified fractions (collected from the bottom of the tube) were performed (Figure 5). LI protein was detected in purified fractions of both constructs (Figure 5A and B); however, again no bands were detected using the 2C7 mAb (Figure 5C and D). The LOS positive control showed a band of -25 kDa and F4 and F5 of each construct also showed bands of the same size; however, there were no distinct bands at -56 kDa - expected size of the chimeras.
[0227] Again, purified fractions (F2-F6) were prepared for EM, as well as the crude extract - for both constructs. Few VLPs were observed in F2 and F3, with mainly capsomeres observed particularly in F4-F6 (Figure 6). There were also more plant aggregates present in the later fractions. The presence of capsomeres is not too surprising as the h4 helix is critical for assembly of T=7 VLPs (Li et al., 1997). (Note: capsomeres have also been shown to be immunogenic.)
[0228] To determine if the 2C7 peptide is being displayed on the VLP / capsomere surface (as western blot results were negative), ELIS As were performed with native samples. Crude and purified fractions (lOOuL / well) were used as coating antigen and LOS peptide (5ug / well) as a positive control. 2C7 mAb was used as primary antibody (1:200). The ELISA worked as the LOS positive control gave a signal, but the experimental samples were all negative as they had similar absorbance reading as the background coating buffer (CB) control (Figure 7).
[0229] Small-scale expression 2
[0230] In an attempt to improve protein expression of the HPV-Ngchimeras, the infiltration of all 8 generation I constructs was repeated and a protein expression time trial was conducted. Plants were syringe infiltrated at OD600 0.75 and co-infiltrated with NSs silencing suppressor at OD600 0.25. Leaf discs were harvested 3,5,7 and 9 days post infiltration (dpi) and crude extract analysed for LI protein by western blot (Figure 8).
[0231] As previously observed, 2C7 mAb was unable to detect the 2C7 peptide in denaturing gels (data not shown), therefore a dot blot analysis was performed to compare denatured vs non-denatured crude samples (Figure 9). As these were crude extracts the dots were quite green. But one can clearly see the detection of protein in the non-denatured samples, observed as darker spots.
[0232] Large-scale expression 2
[0233] From the small-scale expression 2 results, as well as the phenotype of the plants (data not shown), only the CTP constructs were continued for analyses. Five plants / construct were vacuum infiltrated at OD600 0.75 / NSs OD600 0.25 and harvested 5 dpi. Phenotype of the leaves was more pronounced (compared to Figure 2) as the plants have been infiltrated with a higher concentration of recombinant Agrobacterium culture.
[0234] All constructs were purified by density gradient ultracentrifugation and LI and 2C7 protein detected by western blot (Figure 11) and dot blot of non-denatured samples (Figure 12). Note: each construct’s biomass yield differed at harvesting (DE_i 19 g, DE_s 12 g, h4_i 16 g and h4_s 7 g). LI protein was detected in F2-F6 of CTP LL2C7 DE_i and h4_i constructs (Figure 11), while the 2C7 peptide was detected initially only in F2-F4 of CTP LL2C7 DE_i, and following overnight detection in F2-F4 of CTP LL2C7 DE_s and h4_i (Figure 12). The differing starting biomass explains why LI protein is not seen in the CTP LL2C7 DE_s and h4_s constructs. Based on the L1 western blot and 2C7 dot blot results, samples from CTP LI :2C7 DE_i and h4_i for EM were prepared (Figure 13). Finally, it looks like there are some VLPs such as CTP L1:2C7 DE_i shows the most promise with VLPs 35-45 nm.
[0235] Large-scale expression 3
[0236] To make fair comparisons across all constructs, CTP gen I infiltrations were repeated, and 30 g leaf material was harvested. The plant phenotype (data not shown) was similar to that observed in large-scale expression 2 (Figure 10). Biomass was purified as described above and LI and 2C7 protein detected by western and dot blot (Figure 14). Surprisingly, LI signal in the western blots for CTP LI :2C7 DE_i , DE_s and h4_s was not detected, but the 2C7 peptide was detected across all constructs, with CTP L1:2C7 DE_i showing the strongest signal.
[0237] EM was prepared for all constructs (Figure 15). And again, CTP L1:2C7 DE_i showed the best VLPs. VLPs were also observed in CTP L1:2C7 DE_s (but these were more heterologous in shape and size), with the CTP L1:2C7 h4_i and h4_s constructs showing small VLPs / capsomeres / aggregates .
[0238] Generation II
[0239] Gen II constructs were designed after obtaining generation I large-scale expression 2 results. Additionally, HPV- LI has 2 Cys residues at positions 175 and 428 which are critical for assembly and the stability of the virion (Bishop et al., 2007). It was contemplated that the Cys residues flanking the mimitope were interfering with the formation of disulfide bonds between Cys175and Cys428of L1
[0240] Sunita et al. had previously fused the 2C7 mimitope on its own to complement C3d and were able to detect the peptide using the 2C7 mAb, therefore indicating the detection of the peptide if it’s not constrained in a circular structure. From this, 4 new L1:2C7 genes were synthesized (Figure IB - generation II).
[0241] Large-scale expression 1
[0242] Based on the gen I optimization results, all gen II constructs (except pRIC3 L1:2C7 h4_s*) were infiltrated at OD600 0.75, with NSs co-infiltration at OD600 0.25. Twelve to fifteen plants per construct were infiltrated.
[0243] At 5 dpi, 30g of biomass was harvested and purified as described above, and LI and 2C7 protein detected by western blot (Figure 17) and dot blot (Figure 18). LI expression was greater in the CTP versus the pRIC3 infiltrated plants. This is due to the greater leaf tissue necrosis observed in the pRIC3 constructs. The 2C7 dot blots show detection of the 2C7 peptide mainly in the CTP constructs, with CTP L1:2C7 DE_i showing the greatest reaction intensity.
[0244] Purified fractions of all gen II constructs were prepared for EM (Figure 19). CTP LI :2C7 DE_i and DE_s constructs showed structures that most assembled VLPs; however, the VLPs were irregularly shaped. Aggregates were mainly observed for CTP L1:2C7 h4_i and h4_s. The pRIC3 chimeras are mostly assembled into capsomeres.
[0245] Conclusions
[0246] A total of 16 constructs were generated. All constructs have been evaluated with the exception of pRIC3 LI :2C7 h4_s gen II, which has failed to grow in liquid medium. The plant phenotype is more pronounced in pRIC3 constructs - and this affects biomass yields.
[0247] Generation I CTP chimeras show the best results, with CTP L1:2C7 DE_i showing the best expression of the 2C7 mimitope and the formation of VLPs.
[0248] Deletion of the residues flanking the 2C7 mimitope appears to have a considerable effect on VLP formation as evidenced by the generation II constructs.
[0249] Example 4: Purification of CTP L1:2C7 DE_i generation I - Lead HPV-2Vg (Part I)
[0250] Based on the results of Example 3, CTP L1:2C7 gen I was chosen as the lead vaccine. In addition, LI only VLPs (CTP hLl) and CTP empty vector were purified as a positive and negative control, respectively.
[0251] Results
[0252] Detection of LI and 2C7 proteins
[0253] Whole Nicotiana benthamiana (N. benthamiana) plants were vacuum infiltrated with the following recombinant Agrobacterium clones: CTP L1:2C7 DE_i (OD600 0.75 - coinfiltrated with NSs silencing suppressor, OD600 0.25), CTP hLl (OD600 0.5) and CTP empty vector (OD600 0.5). Leaves were harvested 5 days post-infiltration (Figure 20).
[0254] • CTP Ll:2C7 DE_i - 180 g
[0255] • CTP hLl - 45 g
[0256] • CTP empty vector - 45 g
[0257] VLPs were purified by density gradient ultracentrifugation and 2 mL fractions collected from the bottom of the tube (I had 3 tubes for CTP LI :2C7 DE_i as I had more starting biomass). LI protein was detected by western blot using anti-Ll Camvir-1 mAb. The 2C7 peptide was detected by dot blot using anti-2C7 mAb (Figure 21).
[0258] VLP formation
[0259] Based on the western and dot blots, grids were prepared for purified fractions 2, 3 and 4 and VLPs visualized by transmission electron microscopy (Figure 22). F2 and F3 showed VLPs -30-45 nm in diameter. The VLPs appear to be breaking up in F2 but are more or less uniform in shape and size in F3. Few VLPs were observed in F4 (Figure 22A). For LI only VLPs, particles -30-45 nm were observed in F2 and F3, with small VLPs observed in F4 (Figure 22B). No VLPs were observed in the CTP empty vector negative control (Figure 22C).
[0260] VLP characterization
[0261] Indirect ELISA was used to determine if the 2C7 peptide was being displayed on the VLP / capsomere surface. In addition, an HPV-16 conformation- specific antibody (H16.V5) was used to confirm VLP assembly (Figure 23). V5 is a major immunodominant epitope used for the assessment of integrity and antigenicity of VLPs.
[0262] The results show that the 2C7 mimitope is being displayed on the surface of the LI :2C7 DE_i VLPs (Figure 23 A, left panel), particularly in F2 and F3 which correlates with fractions that showed VLPs (Figure 22 A). hLl VLPs and CTP empty vector showed little to no binding by the 2C7 mAb (Figure 23A, middle and right panel, respectively). Detection of the V5 epitope on the LL2C7 DE_i VLPs was observed in F2 and F3 (Figure 23B, left panel). The V5 epitope was displayed well on the LI only VLPs and absent in the empty vector (Figure 23B, middle and right panel, respectively).
[0263] Concentration of VLPs
[0264] From the VLP and ELISA results of LL2C7 DE_i, fractions 2 and 3 were separately pooled and banded via ultracentrifugation (Ih, 183 548 x g) above a 50% iodixanol cushion. A very faint band was observed for F3 but none for F2. Samples were taken from the top of each tube and the band sucked of using a needle and syringe (or in the case of F2, sample was sucked off from where the band should be) and ran on an SDS-PAGE gel with a BSA standard curve for quantitation (Figure 24A). The concentrated F2 and F3 bands were not detected, so a western blot was performed to confirm that the protein was still present (Figure 24B). It is evident that for F3, there is still a lot of protein that is not concentrated as the signal in F3T is as intense as that of the F3B signal. A faint signal was detected for F2B, which explains why an actual band may not have been present in the centrifuge tube after concentration.
[0265] EM confirmed that after concentration the L1:2C7 DE_i VLPs are still intact (Figure 25) (samples were only prepared and viewed 2 weeks after concentration, but it looks like the VLPs are stable at 4C for at least 2 weeks).
[0266] Conclusions
[0267] • L1:2C7 DE_i VLPs are similar in morphology to LI only VLPs.
[0268] • LI :2C7 DE_i VLPs display both the 2C7 mimitope and the V5 epitope on their surface.
[0269] • LL2C7 DE_i VLPs appear to be stable at 4C for at least 2 weeks.
[0270] • Concentration and quantitation of VLPs requires optimization.
[0271] Example 5: Purification of CTP L1:2C7 DE_i generation I - Lead HPV-2Vg (Part II)
[0272] In this example, there is purification of 2 batches of LL2C7 DE_i VLPs and several strategies to concentrate and quantify the cVLPs.
[0273] Results
[0274] Detection of LI and 2C7 proteins
[0275] Whole Nicotiana benthamiana plants (30-50) were vacuum infiltrated CTP LL2C7 DE_i (OD600 0.75 - co-infiltrated with NSs silencing suppressor, OD600 0.25). Leaves were harvested 5 days post-infiltration and frozen at -80C for 1-2 weeks before purification.
[0276] • Batch 1 - 250 g
[0277] • Batch 2 - 360 g
[0278] VLPs were purified by density gradient ultracentrifugation and 2 mL fractions collected from the bottom of the tube. LI protein was detected by western blot using anti-Ll Camvir-1 mAb. The 2C7 peptide was detected by dot blot using anti-2C7 mAb (Figure 26). Concentration of VLPs
[0279] Fractions 2-4 (from multiple tubes) were pooled and loaded onto a 50% iodixanol cushion in order to band the VLPs. Samples were centrifuged at 174 500 x g for 3.5h in a SW32Ti rotor. Multiple bands were observed - 2 bands in batch 1 and 4 bands in batch 2 (Figure 27). All bands were sampled and the rest of the tube fractionated from the bottom. All bands and fractions were analyzed by dot blot for LI and 2C7 protein to determine if concentration was successful (Figure 28). LI signal was observed in all fractions; 2C7 protein was mainly observed in all fractions of batch 2.
[0280] Sampled bands were also separated on SDS-PAGE for Coomassie staining and no protein was observed (Figure 29). This absence of protein detection by Coomassie staining has previously been observed for other HPV chimeras.
[0281] All collected fractions and bands were re-pooled to attempt to concentrate the cVLPs by pelleting. Re-pooled samples were pelleted by ultracentrifugation at 174 500 x g for 45 minutes. Pellets were resolubilized in buffer (high salt (0.5M) lx PBS). Quantitation of pellets by Coomassie staining on SDS- PAGE and ponceau staining was attempted (Figure 30). There appears to be a hindrance in any staining of these chimeras. Silver staining has previously been performed.
[0282] A BCA protein assay was performed to quantify the pelleted samples as well as the original fractions 2- 4 (Figure 31). All data were normalized to an iodixanol control as the reagent gives a background reading. Concentrated pellets showed yields between 3-4 g / ml.
[0283] VLP formation
[0284] Grids were prepared for F2-F4 and the pelleted cVLPs, and visualized by transmission electron microscopy (Figure 32). Few VLPs appear to have been assembled. There is a lot of protein aggregation or the presence of capsomeres. The pelleted samples were also particularly difficult to stain. The cVLPs in the fraction samples (F2-F4) are in the same high salt PBS buffer that the pellet was resolubilized in, therefore the buffer should not affect the staining.
[0285] Conclusions
[0286] • The only difference between this purification and previous ones is processing fresh versus frozen infiltrated leaf material - freezing leaves affects VLP integrity
[0287] • BCA protein assay appears to be the best option of quantify cVLPs - could also be quantified via ELISA.
[0288] Example 6: HPV-2Vg chimeric VLPs produced in plants (N. benthamiana)
[0289] This example aimed to access the immunogenicity of the chimeric VLPs that have been expressed and purified from N. benthamiana. Expression and purification:
[0290] The expression was previously optimized and all cloning completed. The final purification method used was gradient ultracentrifugation.
[0291] Results:
[0292] Large scale infiltration and purification of both the chimera and HPV16 was carried out. VLPs were purified as previously described. HPV16 LI and 2C7 protein detected by western and dot blot, respectively (Figure 33). LI expression was observed in both the purified chimera and HPV16 LI samples. 2C7 protein was detected for the chimera and confirmed by the positive controls. Therefore, confirming that the epitope is displayed correctly and detectable by the antibody.
[0293] To confirm the presence of VLP structures, the samples were examined with transmission electron microscopy. These particles are of the appropriate size (~55 nm). The HPV16 LI particles shown in Fig 34B are of the correct size (-55 nm) and are indicated by the orange arrows. There are also various aggregates and mishappen particles (red arrows Figure 34), and capsomeres present in both of these samples. There are no particles visible in the sample purified from plants infiltrated with the empty expression vector (Figure 34).
[0294] The sample was only -50% pure as indicated by the thick bands indicating rubisco in Figure 33. This method of purification produced the best results so far. Ammonium sulphate precipitation was investigated however this method resulted in particle disassembly and only capsomeres, no VLPs. Other buffers at various pH values were tested but resulted in higher purity with reduced yields. The yields achieved by the current method are already low. The yield of expression and production using the density gradient purification method was determined using gel densitometry and resulted in a 400 ug / kg of biomass of HPV16 LI and a yield 480 ug / kg of biomass of the chimera. A significant amount of plants are required for the production of VLPs at a useful concentration.
[0295] Animal Study:
[0296] Using the expressed and purified VLPs 20 six-week-old female BALB / c mice were vaccinated as seen in Figure 35. There were 4 groups of 5 mice per group. The groups were vaccinated with the following: Chimera VLPs + Adjuvant (Alum), Chimera VLPs, HPV16 LI VLPs as the positive control, and empty vector sample (as the negative control). The group vaccinated with the adjuvant only received one dose, whereas the rest of the groups received the 3 doses. Alum was used as the adjuvant as this is the adjuvant used in the commercially produced HPV vaccine. The mice were given 5 pg of antigen diluted in PBS to a total volume of 100 pL which was injected IP 50 pL per leg. Blood was drawn from the mice at the indicated time points and was used for immunological analysis.
[0297] The mice were also challenged with mammalian derived HPV 16 Pseudo virions (PsVs) containing a firefly luciferase reporter gene. These particles were used to test the vaccine for protection against HPV infection.
[0298] Results:
[0299] The sera from the vaccinated mice were analyzed using western and dot blotting for detection of antibodies against both HPV 16 as well as 2C7 peptide and LOS. This showed the presence of antibodies against HPV16 and 2C7 peptide (Figure 36).
[0300] Protection against HPV :
[0301] The sera from the various groups was pooled and all experiments were repeated 3 times. These results represent the average of the repeats. The pre-bleeds of the mice were used as a negative control and compared to the sera taken at the end of the experiment. This showed a significant antibody response against HPV 16 for both the chimera groups and for the HPV 16 positive control group. There was some response seen in the negative control group. This is attributed to elicitation of antibodies against plant proteins (such as rubisco) which then bind to these proteins which exist as impurities in the coating antigen.
[0302] When accessing the antibody titer levels, HPV 16 titers were expressed as the reciprocal of the maximum serum dilution containing higher absorbance readings than that of the corresponding pre-bleed serum at 1:50. The plant derived HPV 16 and the plant-derived chimaera (with adjuvant) elicited anti-Ll titers of 1:204800, and the chimera without the presence of adjuvant elicited anti-Ll titers of 1:51200. The presence of adjuvant increased the antibody titer levels even though these mice only received one vaccine dose, showing that the adjuvant increases the immunogenicity of the vaccine. These levels were comparable to the HPV16 LI vaccinated mice which served as a positive control.
[0303] The results of the challenge experiment show that the chimera provides protection against infection with the HPV PsVs. These results are shown in Figure 38 which shows the images of the mice taken in the IVIS machine and a graph depicting the readings taken by the machine. The images in the IVIS machine show that 3 / 5 mice in the negative control group are expressing the luciferase reporter gene and are therefore infected by 72 hours after inoculation. While all other mice in the chimera groups and the HPV16 control group do not show any infection. Any visible infection that may be seen in these groups is due to the presence of mice feces which shows a signal under the IVIS readings. The readings taken of the signals show that the groups vaccinated with the chimera and with the HPV16 have little variation and are not expressing the reporter gene. Therefore, they have not been infected and the vaccine is providing protection. While the mice vaccinated with the negative control have a large amount of variation and show infection in 3 / 5 mice. The lack of infection in 2 of the mice may be due to ineffective infection. This should be repeated to confirm these results. Due to only 3 out of 5 mice showing infection T-tests on this data do not show significant differences between the negative control (infected group) and the vaccinated groups. Although no significance is seen it is evident from the elicitation of the antibody responses seen above that the vaccine does elicit a protective response against HPV16 LI.
[0304] Protection against 2C7 and LOS:
[0305] The mice sera was assessed for the presence of antibodies specific to 2C7 and LOS using indirect ELISA. The sera from the various groups was pooled and all experiments were repeated 3 times. These results represent the average of the repeats.
[0306] The pre-bleeds of the mice were used as a negative control and compared to the sera taken at the end of the experiment. This showed a significant antibody response against 2C7 and LOS for both the chimera groups. There was no response seen in the HPV16 group and negative control group. This shows that the response seen is specific to the insertion of 2C7 peptide into the chimera.
[0307] When accessing the antibody titer levels, 2C7 and LOS titers were expressed as the reciprocal of the maximum serum dilution containing higher absorbance readings than that of the corresponding pre-bleed serum at 1:50. The chimera elicited antibody titer levels of 1:32000 against 2C7 coating antigen both with and without the presence of adjuvant (Figure 39). The vaccination without adjuvant elicited a slightly higher response, which may be due to the difference in doses received, as the adjuvant group only received one dose of the vaccine.
[0308] The detection of antibodies elicited against LOS was done with indirect ELISA. The anti-LOS titers were expressed as the reciprocal of the maximum serum dilution containing higher absorbance readings than that of the corresponding pre-bleed serum at 1:200. The pre-bleeds showed no response against the LOS (Figure 40). The negative controls, HPV16 and the plant only, elicited no response against LOS. The chimera elicited antibody titer levels of 1:4000 both with and without the presence of adjuvant (Figure 40). As with the anti-2C7 titer levels vaccination without adjuvant elicited a slightly higher response.
[0309] Summary
[0310] In summary, the vaccines were tested for protective immunogenicity against HPV16 and 2C7 and LOS which could confer protection against Neisseria gonorrhoeae. The experiment showed that antibodies were elicited against not only HPV but also against both 2C7 peptide and LOS. The antibodies elicited against HPV16 showed to be protective against infection. In some embodiments, a non-limiting source of production systems could be used for the production of the particles.
[0311] It will be apparent to those skilled in the art that various modifications and variations can be made in the present disclosure without departing from the scope or spirit of the invention. Other embodiments of the disclosure will be apparent to those skilled in the art from consideration of the specification and practice of the methods disclosed herein. It is intended that the specification and examples be considered as exemplary only, with a true scope and spirit of the invention being indicated by the following claims.
[0312] SEQUENCES
[0313] 1. SEQ ID NO: 1 - L1:2C7 DE_insertion (i) Generation 1 - nucleic acid
[0314] ATGAGTCTGTGGCTGCCATCTGAGGCAACCGTGTACCTGCCACCTGTGCCTGTGA
[0315] GCAAGGTGGTGTCCACCGACGAGTATGTGGCCCGGACAAATATCTACTATCACG
[0316] CAGGCACAAGCAGACTGCTGGCAGTGGGCCACCCTTACTTCCCAATCAAGAAGC
[0317] CTAACAATAACAAGATCCTGGTGCCAAAGGTGAGCGGCCTGCAGTATAGGGTGT
[0318] TCCGCATCCACCTGCCAGATCCCAATAAGTTCGGCTTTCCAGACACCTCCTTTTAC
[0319] AACCCCGATACACAGAGGCTGGTGTGGGCATGCGTGGGAGTGGAAGTGGGAAGG
[0320] GGCCAGCCACTGGGCGTGGGCATCTCCGGCCACCCCCTGCTGAATAAGCTGGAC
[0321] GATACCGAGAACTGTGGCCCTATCCCAGTGCTGGACGAGAACGGACTGTTTGCA
[0322] CCAGGACCTTGCGCATCCGCCTACGCAGCAAATGCAGGAGTGGACAACAGGGAG
[0323] TGTATCTCTATGGATTATAAGCAGACCCAGCTGTGCCTGATCGGCTGTAAGCCAC
[0324] CAATCGGAGAGCACTGGGGCAAGGGATCTCCATGCACAAATGTGGCCGTGAACC
[0325] CTGGCGACTGTCCTCCACTGGAGCTGATCAATACCGTGATCCAGGACGGCGATAT
[0326] GGTGGACACAGGCTTCGGCGCCATGGACTTCACCACCCTGCAGGCCAACAAGTC
[0327] TGAGGTGCCTCTGGACATCTGCACCAGCATCTGTAAGTACCCTGATTATATCAAG
[0328] ATGGTGAGCGAGCCATACGGCGATTCCCTGTTCTTTTATCTGCGGAGAGAGCAGA
[0329] TGTTCGTGAGGCACCTGTTTAATAGGGCAGGAGCAGTGGGAGAGAACGTGCCTG
[0330] ACGATCTGTACATCAAGGGCTCCGGCTCTACCGCCAATCTGGCCAGCTCCAACTA
[0331] TTTCCCAACCCCCAGCGGCTCCATGGTGACAAGCGACGCCCAGATCTTTAATAAG
[0332] CCATACTGGCTGCAGAGGGCCCAGGGCCACAATAACGGCATCTGCTGGGGCAAT
[0333] CAGCTGTTCGTGACCGTGGTGGATACCACACGCTCTACAAACATGAGCCTGTGCG
[0334] CCGCCATCTCTACCAGCGAGACCACATACAAGAACACAAACTTTAAGGAGTACC
[0335] TGCGGCACGGCGAGGAGTATGACCTGCAGTTCATCTTTCAGCTGTGCAAGATCAC
[0336] CCTGACAGCCGATGTGATGACCTACATCCACTCCATGAACAGCACAATCCTGGAG
[0337] GACTGGAACTTCGGACTGCAGCCACCTCCAGGAGGCACCCTGGAGGATACATAT
[0338] AGGTTTGTGACCTCTCAGGCCATCGCCTGTCAGAAGCACACACCACCTGCACCAA
[0339] AGGAGGACCCTCTGAAGAAGTACACCTTCTGGGAGGTGAACCTGAAGGAGAAGT
[0340] TTAGCGCCGACCTGGATCAGTTCCCACTGGGACGGAAGTTTCTGCTGCAGGCCGG
[0341] CCTGAAGGCCAAGCCAAAGTTCACCCTGGGCAAGAGAAAGGCCACCCCCACCAC
[0342] ATCTAGCACATCCACCACAGCCAAG CGGAAGAAGAGAAAGCTGTAA 2. SEQ ID NO: 2 - L1:2C7 DE_i Generation 1 - amino acid
[0343] MSLWLPSEATVYLPPVPVSKVVSTDEYVARTNIYYHAGTSRLLAVGHPYFPIKKPNN
[0344] NKILVPKVSGLQYRVFRIHLPDPNKFGFPDTSFYNPDTQRLVWACVGVEVGRGQPLG
[0345] VGISGHPLLNKLDDTENCGPIPVLDENGLFAPGPCASAYAANAGVDNRECISMDYKQ
[0346] TQLCLIGCKPPIGEHWGKGSPCTNVAVNPGDCPPLELINTVIQDGDMVDTGFGAMDF
[0347] TTLQANKSEVPLDICTSICKYPDYIKMVSEPYGDSLFFYLRREQMFVRHLFNRAGAV
[0348] GENVPDDLYIKGSGSTANLASSNYFPTPSGSMVTSDAQIFNKPYWLQRAQGHNNGIC
[0349] WGNQLFVTVVDTTRSTNMSLCAAISTSETTYKNTNFKEYLRHGEEYDLQFIFQLCKIT
[0350] LTADVMTYIHSMNSTILEDWNFGLQPPPGGTLEDTYRFVTSQAIACQKHTPPAPKEDP
[0351] LKKYTFWEVNLKEKFSADLDQFPLGRKFLLQAGLKAKPKFTLGKRKATPTTSSTSTT
[0352] AKRKKRKL*
[0353] 3. SEQ ID NO: 3 - L1:2C7 DE_substitution (s) Generation 1 - nucleic acid
[0354] ATGAGTCTGTGGCTGCCATCTGAGGCAACCGTGTACCTGCCACCTGTGCCTGTGA
[0355] GCAAGGTGGTGTCCACCGACGAGTATGTGGCCCGGACAAACATCTACTATCACG
[0356] CAGGCACAAGCAGACTGCTGGCAGTGGGCCACCCTTACTTCCCAATCAAGAAGC
[0357] CTAACAATAACAAGATCCTGGTGCCAAAGGTGTCCGGCCTGCAGTATAGGGTGTT
[0358] CCGCATCCACCTGCCAGATCCCAATAAGTTCGGCTTTCCAGACACCTCTTTTTACA
[0359] ACCCCGATACACAGAGGCTGGTGTGGGCATGCGTGGGAGTGGAAGTGGGAAGGG
[0360] GCCAGCCACTGGGAGTGGGAATCTCTGGACACCCACTGCTGAATAAGCTGGACG
[0361] ATACCGAGTGCGGCCCTATCCCAGTGCTGGACGAGAACGGACTGTTTGCACCAG
[0362] GACCTTGTATGGATTATAAGCAGACCCAGCTGTGCCTGATCGGCTGTAAGCCACC
[0363] AATCGGAGAGCACTGGGGCAAGGGATCCCCATGCACAAATGTGGCCGTGAACCC
[0364] TGGCGACTGTCCTCCACTGGAGCTGATCAATACCGTGATCCAGGACGGCGATATG
[0365] GTGGACACAGGCTTCGGCGCCATGGACTTCACCACCCTGCAGGCCAACAAGTCT
[0366] GAGGTGCCTCTGGACATCTGCACCAGCATCTGTAAGTACCCTGATTATATCAAGA
[0367] TGGTGAGCGAGCCATACGGCGATTCCCTGTTCTTTTATCTGCGGAGAGAGCAGAT
[0368] GTTCGTGAGGCACCTGTTTAATAGGGCAGGAGCAGTGGGAGAGAACGTGCCTGA
[0369] CGATCTGTACATCAAGGGCTCCGGCTCTACCGCCAATCTGGCCAGCTCCAACTAT
[0370] TTCCCAACCCCCAGCGGCTCCATGGTGACAAGCGACGCCCAGATCTTTAATAAGC
[0371] CATACTGGCTGCAGAGGGCCCAGGGCCACAATAACGGCATCTGCTGGGGCAATC
[0372] AGCTGTTCGTGACCGTGGTGGATACCACACGCTCTACAAACATGAGCCTGTGCGC
[0373] CGCCATCTCTACCAGCGAGACCACATACAAGAACACAAACTTTAAGGAGTACCT GCGGCACGGCGAGGAGTATGACCTGCAGTTCATCTTTCAGCTGTGCAAGATCACC
[0374] CTGACAGCCGATGTGATGACCTACATCCACTCCATGAACAGCACAATCCTGGAG
[0375] GACTGGAACTTCGGACTGCAGCCACCTCCAGGAGGCACCCTGGAGGATACATAT
[0376] AGGTTTGTGACCAGCCAGGCCATCGCCTGTCAGAAGCACACACCACCTGCACCA
[0377] AAGGAGGACCCTCTGAAGAAGTACACCTTCTGGGAGGTGAACCTGAAGGAGAAG
[0378] TTTTCCGCCGACCTGGATCAGTTCCCACTGGGACGGAAGTTTCTGCTGCAGGCCG
[0379] GCCTGAAGGCCAAGCCAAAGTTCACCCTGGGCAAGAGAAAGGCCACCCCCACCA
[0380] CATCTAGCACATCCACCACAGCCAAGCGGAAGAAGAGAAAGCTGTAA
[0381] 4. SEQ ID NO: 4 - L1:2C7 DE_s Generation 1 - amino acid
[0382] MSLWLPSEATVYLPPVPVSKVVSTDEYVARTNIYYHAGTSRLLAVGHPYFPIKKPNN
[0383] NKLLVPKVSGLQYRVFRIHLPDPNKFGFPDTSFYNPDTQRLVWACVGVEVGRGQPLG VGISGHPLLNKLDDTECGPIPVLDENGLFAPGPCMDYKQTQLCLIGCKPPIGEHWGK
[0384] GSPCTNVAVNPGDCPPLELINTVIQDGDMVDTGFGAMDFTTLQANKSEVPLDICTSIC KYPDYIKMVSEPYGDSLFFYLRREQMFVRHLFNRAGAVGENVPDDLYIKGSGSTAN LAS SN YFPTPS GSM VTS D AQIFNKP YWLQRAQGHNNGIC WGNQLFVTVVDTTRSTN MSLCAAISTSETTYKNTNFKEYLRHGEEYDLQFIFQLCKITLTADVMTYIHSMNSTILE
[0385] DWNFGLQPPPGGTLEDTYRFVTSQAIACQKHTPPAPKEDPLKKYTFWEVNLKEKFSA DLDQFPLGRKFLLQAGLKAKPKFTLGKRKATPTTSSTSTTAKRKKRKL*
[0386] 5. SEQ ID NO: 5 - L1:2C7 h4_i Generation I - nucleic acid
[0387] ATGAGTCTGTGGCTGCCATCTGAGGCAACCGTGTACCTGCCACCTGTGCCTGTGA
[0388] GCAAGGTGGTGTCCACCGATGAGTATGTGGCCCGGACAAATATCTACTATCACGC
[0389] AGGCACATCCAGACTGCTGGCAGTGGGCCACCCTTACTTCCCAATCAAGAAGCCT
[0390] AACAATAACAAGATCCTGGTGCCAAAGGTGTCCGGCCTGCAGTATAGGGTGTTC
[0391] CGCATCCACCTGCCAGACCCCAATAAGTTCGGCTTTCCAGACACCTCTTTTTACA
[0392] ACCCCGATACACAGAGGCTGGTGTGGGCATGCGTGGGAGTGGAAGTGGGAAGGG
[0393] GCCAGCCACTGGGCGTGGGCATCTCCGGCCACCCCCTGCTGAATAAGCTGGACG
[0394] ATACCGAGAACGCCTCTGCCTACGCAGCAAATGCAGGAGTGGACAACAGGGAGT
[0395] GTATCAGCATGGATTATAAGCAGACCCAGCTGTGCCTGATCGGCTGTAAGCCACC
[0396] ATCGGAGAGCACTGGGGCAAGGGATCTCCATGCACAAATGTGGCCGTGAACCCT GGCGATTGTCCTCCACTGGAGCTGATCAATACCGTGATCCAGGACGGCGATATGG
[0397] TGGACACAGGCTTCGGCGCCATGGACTTCACCACCCTGCAGGCCAACAAGTCTG AGGTGCCTCTGGACATCTGCACCAGCATCTGTAAGTACCCTGATTATATCAAGAT
[0398] GGTGAGCGAGCCATACGGCGACTCCCTGTTCTTTTATCTGCGGAGAGAGCAGATG
[0399] TTCGTGAGGCACCTGTTTAATAGGGCAGGAGCAGTGGGAGAGAACGTGCCTGAC
[0400] GATCTGTACATCAAGGGCTCCGGCTCTACCGCCAATCTGGCCAGCTCCAACTATT
[0401] TCCCTACCCCAAGCGGCTCCATGGTGACAAGCGATGCCCAGATCTTTAACAAGCC
[0402] ATACTGGCTGCAGAGGGCCCAGGGCCACAATAACGGCATCTGCTGGGGCAATCA
[0403] GCTGTTCGTGACCGTGGTGGACACCACACGCTCTACAAACATGAGCCTGTGCGCC
[0404] GCCATCTCTACCAGCGAGACCACATACAAGAACACAAACTTTAAGGAGTACCTG
[0405] CGGCACGGCGAGGAGTATGACCTGCAGTTCATCTTTCAGCTGTGCAAGATCACCC
[0406] TGACAGCCGATGTGATGACCTACATCCACTCCATGAACAGCACAATCCTGGAGG
[0407] ACTGGAACTTCGGCCTGCAGCCACCTCCAGGAGGCACCCTGTGCGGACCAATCCC
[0408] TGTGCTGGACGAGAATGGACTGTTCGCACCAGGACCATGCGAGGATACCTATAG
[0409] GTTTGTGACAAGCCAGGCCATCGCATGTCAGAAGCACACCCCACCTGCACCAAA
[0410] GGAGGACCCTCTGAAGAAGTACACATTCTGGGAGGTGAACCTGAAGGAGAAGTT
[0411] TTCCGCCGACCTGGATCAGTTCCCACTGGGACGGAAGTTTCTGCTGCAGGCCGGC
[0412] CTGAAGGCCAAGCCAAAGTTTACCCTGGGCAAGAGAAAGGCCACCCCCACCACA
[0413] TCTAGCACAAGCACCACAGCCAAGCGGAAGAAGAGAAAGCTGTAA
[0414] 6. SEQ ID NO: 6 - LI :2C7 h4_i Generation I - amino acid
[0415] MSLWLPSEATVYLPPVPVSKVVSTDEYVARTNIYYHAGTSRLLAVGHPYFPIKKPNN
[0416] NKILVPKVSGLQYRVFRIHLPDPNKFGFPDTSFYNPDTQRLVWACVGVEVGRGQPLG
[0417] VGISGHPLLNKLDDTENASAYAANAGVDNRECISMDYKQTQLCLIGCKPPIGEHWG
[0418] KGSPCTNVAVNPGDCPPLELINTVIQDGDMVDTGFGAMDFTTLQANKSEVPLDICTSI
[0419] CKYPDYIKMVSEPYGDSLFFYLRREQMFVRHLFNRAGAVGENVPDDLYIKGSGSTA
[0420] NLASSNYFPTPSGSMVTSDAQIFNKPYWLQRAQGHNNGICWGNQLFVTVVDTTRST
[0421] NMSLCAAISTSETTYKNTNFKEYLRHGEEYDLQFIFQLCKITLTADVMTYIHSMNSTI
[0422] LEDWNFGLQPPPGGTLCGPIPVLDENGLFAPGPCEDTYRFVTSQAIACQKHTPPAPKE
[0423] DPLKKYTFWEVNLKEKFSADLDQFPLGRKFLLQAGLKAKPKFTLGKRKATPTTSSTS
[0424] TTAKRKKRKL*
[0425] 7. SEQ ID NO: 7 - LI :2C7 h4_s Generation I - nucleic acid
[0426] ATGAGTCTGTGGCTGCCATCTGAGGCAACCGTGTACCTGCCACCTGTGCCTGTGA
[0427] GCAAGGTGGTGTCCACCGATGAGTATGTGGCCCGGACAAATATCTACTATCACGC AGGCACATCCAGACTGCTGGCAGTGGGCCACCCTTACTTCCCAATCAAGAAGCCT
[0428] AACAATAACAAGATCCTGGTGCCAAAGGTGTCCGGCCTGCAGTATAGGGTGTTC
[0429] CGCATCCACCTGCCAGACCCCAATAAGTTCGGCTTTCCAGACACCTCTTTTTACA
[0430] ACCCCGATACACAGAGGCTGGTGTGGGCATGCGTGGGAGTGGAAGTGGGAAGGG
[0431] GCCAGCCACTGGGCGTGGGCATCTCCGGCCACCCCCTGCTGAATAAGCTGGACG
[0432] ATACCGAGAACGCCTCTGCCTACGCAGCAAATGCAGGAGTGGACAACAGGGAGT
[0433] GTATCAGCATGGATTATAAGCAGACCCAGCTGTGCCTGATCGGCTGTAAGCCACC
[0434] AATCGGAGAGCACTGGGGCAAGGGATCTCCATGCACAAATGTGGCCGTGAACCC
[0435] TGGCGATTGTCCTCCACTGGAGCTGATCAATACCGTGATCCAGGACGGCGATATG
[0436] GTGGACACAGGCTTCGGCGCCATGGACTTCACCACCCTGCAGGCCAACAAGTCT
[0437] GAGGTGCCTCTGGACATCTGCACCAGCATCTGTAAGTACCCTGATTATATCAAGA
[0438] TGGTGAGCGAGCCATACGGCGACTCCCTGTTCTTTTATCTGCGGAGAGAGCAGAT
[0439] GTTCGTGAGGCACCTGTTTAATAGGGCAGGAGCAGTGGGAGAGAACGTGCCTGA
[0440] CGATCTGTACATCAAGGGCTCCGGCTCTACCGCCAATCTGGCCAGCTCCAACTAT
[0441] TTCCCTACCCCAAGCGGCTCCATGGTGACAAGCGATGCCCAGATCTTTAACAAGC
[0442] CATATTGGCTGCAGAGGGCCCAGGGCCACAATAACGGCATCTGCTGGGGCAATC
[0443] AGCTGTTCGTGACCGTGGTGGACACCACACGCTCTACAAACATGAGCCTGTGCGC
[0444] CGCCATCTCTACCAGCGAGACCACATACAAGAACACAAACTTTAAGGAGTACCT
[0445] GAGGCACGGCGAGGAGTATGACCTGCAGTTCATCTTTCAGCTGTGCAAGATCACC
[0446] CTGACAGCCGATGTGATGACCTACATCCACTCCATGAACAGCACAATCCTGGAG
[0447] GACTGGAACTTCGGCCTGCAGCCACCTCCAGGAGGAACCTGCGGACCCATCCCT
[0448] GTGCTGGATGAGAATGGACTGTTTGCACCAGGACCATGTACCCCACCTGCACCAA
[0449] AGGAGGACCCTCTGAAGAAGTACACATTCTGGGAGGTGAACCTGAAGGAGAAGT
[0450] TTAGCGCCGACCTGGATCAGTTCCCACTGGGACGGAAGTTTCTGCTGCAGGCCGG
[0451] CCTGAAGGCCAAGCCAAAGTTCACCCTGGGCAAGAGAAAGGCCACCCCCACCAC
[0452] ATCTAGCACATCCACCACAGCCAAGCGGAAGAAGAGAAAGCTGTAA
[0453] 8. SEQ ID NO: 8 - LI :2C7 h4_s Generation I - amino acid
[0454] MSLWLPSEATVYLPPVPVSKVVSTDEYVARTNIYYHAGTSRLLAVGHPYFPIKKPNN
[0455] NKILVPKVSGLQYRVFRIHLPDPNKFGFPDTSFYNPDTQRLVWACVGVEVGRGQPLG
[0456] VGISGHPLLNKLDDTENASAYAANAGVDNRECISMDYKQTQLCLIGCKPPIGEHWG
[0457] KGSPCTNVAVNPGDCPPLELINTVIQDGDMVDTGFGAMDFTTLQANKSEVPLDICTSI
[0458] CKYPDYIKMVSEPYGDSLFFYLRREQMFVRHLFNRAGAVGENVPDDLYIKGSGSTA NLASSNYFPTPSGSMVTSDAQIFNKPYWLQRAQGHNNGICWGNQLFVTVVDTTRST
[0459] NMSLCAAISTSETTYKNTNFKEYLRHGEEYDLQFIFQLCKITLTADVMTYIHSMNSTI
[0460] LEDWNFGLQPPPGGTCGPIPVLDENGLFAPGPCTPPAPKEDPLKKYTFWEVNLKEKFS
[0461] ADLDQFPLGRKFLLQAGLKAKPKFTLGKRKATPTTSSTSTTAKRKKRKL*
[0462] 9. SEQ ID NO: 9 - LI :2C7 DE_i Generation II - nucleic acid
[0463] ATGAGCCTGTGGCTGCCTAGCGAGGCAACCGTGTACCTGCCACCTGTGCCAGTGA
[0464] GCAAGGTGGTGTCCACCGACGAGTATGTGGCCCGGACAAACATCTACTATCACG
[0465] CAGGCACATCCAGACTGCTGGCAGTGGGCCACCCCTACTTCCCTATCAAGAAGCC
[0466] CAACAATAACAAGATCCTGGTGCCTAAGGTGTCCGGCCTGCAGTATAGGGTGTTC
[0467] CGCATCCACCTGCCAGATCCCAACAAGTTCGGCTTTCCTGACACCTCTTTTTACAA
[0468] TCCAGATACACAGAGGCTGGTGTGGGCATGCGTGGGAGTGGAAGTGGGAAGGGG
[0469] CCAGCCTCTGGGAGTGGGAATCTCCGGACACCCACTGCTGAATAAGCTGGACGA
[0470] TACCGAGAACATCCCAGTGCTGGACGAGAATGGACTGTTTGCACCAGCATCTGCC
[0471] TACGCAGCAAATGCAGGAGTGGACAACAGGGAGTGTATCAGCATGGATTATAAG
[0472] CAGACCCAGCTGTGCCTGATCGGCTGTAAGCCACCAATCGGAGAGCACTGGGGC
[0473] AAGGGCTCTCCATGCACAAATGTGGCCGTGAACCCCGGCGATTGTCCTCCACTGG
[0474] AGCTGATCAACACCGTGATCCAGGACGGCGATATGGTGGACACAGGCTTCGGCG
[0475] CCATGGACTTCACCACCCTGCAGGCCAATAAGAGCGAGGTGCCTCTGGACATCTG
[0476] CACCTCCATCTGTAAGTACCCCGATTATATCAAGATGGTGTCCGAGCCTTACGGC
[0477] GACTCTCTGTTCTTTTATCTGCGGAGAGAGCAGATGTTCGTGAGGCACCTGTTTA
[0478] ACAGGGCAGGAGCAGTGGGAGAGAATGTGCCAGACGATCTGTACATCAAGGGCT
[0479] CCGGCTCTACCGCCAATCTGGCCAGCTCCAACTATTTCCCTACCCCAAGCGGCTC
[0480] CATGGTGACAAGCGACGCCCAGATCTTTAACAAGCCATACTGGCTGCAGAGGGC
[0481] ACAGGGACACAATAACGGCATCTGCTGGGGCAACCAGCTGTTCGTGACCGTGGT
[0482] GGATACCACACGCTCTACAAATATGAGCCTGTGCGCCGCCATCTCTACCAGCGAG
[0483] ACCACATACAAGAACACAAACTTTAAGGAGTACCTGCGGCACGGCGAGGAGTAT
[0484] GACCTGCAGTTCATCTTTCAGCTGTGCAAGATCACCCTGACAGCCGATGTGATGA
[0485] CCTACATCCACTCCATGAACTCTACAATCCTGGAGGACTGGAATTTCGGACTGCA
[0486] GCCACCTCCAGGAGGCACCCTGGAGGATACATATAGGTTTGTGACCTCTCAGGCC
[0487] ATCGCCTGTCAGAAGCACACACCCCCTGCCCCAAAGGAGGACCCCCTGAAGAAG
[0488] TACACCTTCTGGGAAGTGAATCTGAAGGAGAAGTTTAGCGCCGACCTGGATCAG
[0489] TTCCCACTGGGACGGAAGTTTCTGCTGCAGGCAGGCCTGAAGGCAAAGCCAAAG TTCACCCTGGGCAAGAGAAAGGCCACCCCTACCACATCTAGCACATCCACCACA
[0490] GCCAAGCGGAAGAAGAGAAAGCTGTGA
[0491] 10. SEQ ID NO: 10 - L1:2C7 DE_i Generation II - amino acid
[0492] MSLWLPSEATVYLPPVPVSKVVSTDEYVARTNIYYHAGTSRLLAVGHPYFPIKKPNN
[0493] NKILVPKVSGLQYRVFRIHLPDPNKFGFPDTSFYNPDTQRLVWACVGVEVGRGQPLG
[0494] VGISGHPLLNKLDDTEN1PVLDENGLFAPASAYAANAGVDNREC1SMDYKQTQLCL1
[0495] GCKPPIGEHWGKGSPCTNVAVNPGDCPPLELINTVIQDGDMVDTGFGAMDFTTLQA
[0496] NKSEVPLDICTSICKYPDYIKMVSEPYGDSLFFYLRREQMFVRHLFNRAGAVGENVP
[0497] DDLYIKGSGSTANLASSNYFPTPSGSMVTSDAQIFNKPYWLQRAQGHNNGICWGNQ
[0498] LFVTVVDTTRSTNMSLCAAISTSETTYKNTNFKEYLRHGEEYDLQFIFQLCKITLTAD
[0499] VMTYIHSMNSTILEDWNFGLQPPPGGTLEDTYRFVTSQAIACQKHTPPAPKEDPLKK
[0500] YTFWEVNLKEKFSADLDQFPLGRKFLLQAGLKAKPKFTLGKRKATPTTSSTSTTAKR
[0501] KKRKL*
[0502] 11. SEQ ID NO: 11 - L1:2C7 DE_s Generation II - nucleic acid
[0503] ATGAGCCTGTGGCTGCCTTCCGAGGCAACCGTGTACCTGCCACCTGTGCCAGTGA
[0504] GCAAGGTGGTGTCCACCGACGAGTATGTGGCCCGGACAAACATCTACTATCACG
[0505] CCGGCACATCTAGACTGCTGGCCGTGGGCCACCCCTACTTCCCTATCAAGAAGCC
[0506] CAACAATAACAAGATCCTGGTGCCTAAGGTGTCTGGCCTGCAGTATAGGGTGTTC
[0507] CGCATCCACCTGCCAGATCCCAATAAGTTCGGCTTTCCTGACACCAGCTTTTACA
[0508] ACCCAGATACACAGAGGCTGGTGTGGGCATGCGTGGGAGTGGAAGTGGGAAGG
[0509] GGCCAGCCTCTGGGAGTGGGAATCTCTGGACACCCACTGCTGAATAAGCTGGAC
[0510] GATACCGAGATCCCAGTGCTGGACGAGAACGGCCTGTTTGCCCCCATGGATTATA
[0511] AGCAGACACAGCTGTGCCTGATCGGCTGTAAGCCACCAATCGGAGAGCACTGGG
[0512] GCAAGGGATCCCCATGCACCAATGTGGCCGTGAACCCCGGCGACTGTCCTCCACT
[0513] GGAGCTGATCAATACCGTGATCCAGGACGGCGATATGGTGGACACAGGCTTCGG
[0514] CGCCATGGACTTCACCACCCTGCAGGCCAACAAGAGCGAGGTGCCTCTGGACAT
[0515] CTGCACCTCCATCTGTAAGTACCCCGATTATATCAAGATGGTGTCCGAGCCTTAC
[0516] GGCGATTCTCTGTTCTTTTATCTGCGGAGAGAGCAGATGTTCGTGAGGCACCTGT
[0517] TTAATAGGGCAGGAGCAGTGGGAGAGAACGTGCCAGACGATCTGTACATCAAGG
[0518] GCTCCGGCTCTACCGCCAATCTGGCCAGCTCCAACTATTTCCCTACCCCAAGCGG
[0519] CTCCATGGTGACAAGCGACGCCCAGATCTTTAATAAGCCATACTGGCTGCAGAG GGCACAGGGACACAATAACGGCATCTGCTGGGGCAATCAGCTGTTCGTGACCGT
[0520] GGTGGATACCACACGCTCTACAAACATGAGCCTGTGCGCCGCCATCTCTACCAGC
[0521] GAGACCACATACAAGAACACAAACTTTAAGGAGTACCTGCGGCACGGCGAGGAG
[0522] TATGACCTGCAGTTCATCTTTCAGCTGTGCAAGATCACCCTGACAGCCGATGTGA
[0523] TGACCTACATCCACTCCATGAACAGCACAATCCTGGAGGACTGGAACTTCGGACT
[0524] GCAGCCACCTCCAGGAGGCACCCTGGAGGATACATATAGGTTTGTGACCAGCCA
[0525] GGCCATCGCCTGTCAGAAGCACACACCCCCTGCCCCAAAGGAGGACCCCCTGAA
[0526] GAAGTACACCTTCTGGGAGGTGAACCTGAAGGAGAAGTTTTCCGCCGACCTGGA
[0527] TCAGTTCCCACTGGGACGGAAGTTTCTGCTGCAGGCAGGCCTGAAGGCAAAGCC
[0528] AAAGTTCACCCTGGGCAAGAGAAAGGCCACCCCTACCACATCTAGCACATCCAC
[0529] CACAGCCAAGC GGAAGAAGAGAAAGCTGTGA
[0530] 12. SEQ ID NO: 12 - L1:2C7 DE_ s Generation II - amino acid
[0531] MSLWLPSEATVYLPPVPVSKVVSTDEYVARTNIYYHAGTSRLLAVGHPYFPIKKPNN
[0532] NKILVPKVSGLQYRVFRIHLPDPNKFGFPDTSFYNPDTQRLVWACVGVEVGRGQPLG
[0533] VGISGHPLLNKLDDTEIPVLDENGLFAPMDYKQTQLCLIGCKPPIGEHWGKGSPCTNV
[0534] AVNPGDCPPLELINTVIQDGDMVDTGFGAMDFTTLQANKSEVPLDICTSICKYPDYIK
[0535] MVSEPYGDSLFFYLRREQMFVRHLFNRAGAVGENVPDDLYIKGSGSTANLASSNYFP
[0536] TPSGSMVTSDAQIFNKPYWLQRAQGHNNGICWGNQLFVTVVDTTRSTNMSLCAAIS
[0537] TSETTYKNTNFKEYLRHGEEYDLQFIFQLCKITLTADVMTYIHSMNSTILEDWNFGLQ PPPGGTLEDTYRFVTSQAIACQKHTPPAPKEDPLKKYTFWEVNLKEKFSADLDQFPL GRKFLLQAGLKAKPKFTLGKRKATPTTSSTSTTAKRKKRKL*
[0538] 13. SEQ ID NO: 13 - L1:2C7 h4_i Generation II - nucleic acid
[0539] ATGAGCCTGTGGCTGCCTTCCGAGGCAACCGTGTACCTGCCACCTGTGCCAGTGA
[0540] GCAAGGTGGTGTCCACCGATGAGTATGTGGCCCGGACAAATATCTACTATCACGC
[0541] CGGCACATCTAGACTGCTGGCCGTGGGCCACCCCTACTTCCCTATCAAGAAGCCC
[0542] AACAATAACAAGATCCTGGTGCCTAAGGTGTCTGGCCTGCAGTATAGGGTGTTCC
[0543] GCATCCACCTGCCAGACCCCAATAAGTTCGGCTTTCCTGACACCAGCTTTTACAA
[0544] CCCAGATACACAGAGGCTGGTGTGGGCATGCGTGGGAGTGGAAGTGGGAAGGG
[0545] GCCAGCCTCTGGGAGTGGGAATCTCTGGACACCCACTGCTGAATAAGCTGGACG
[0546] ATACCGAGAACGCCAGCGCCTACGCAGCAAATGCAGGAGTGGACAACAGGGAG
[0547] TGTATCTCCATGGATTATAAGCAGACCCAGCTGTGCCTGATCGGCTGTAAGCCAC CAATCGGAGAGCACTGGGGCAAGGGCTCTCCATGCACAAATGTGGCCGTGAACC
[0548] CCGGCGATTGTCCTCCACTGGAGCTGATCAATACCGTGATCCAGGACGGCGATAT
[0549] GGTGGACACAGGCTTCGGCGCCATGGACTTCACCACCCTGCAGGCCAACAAGAG
[0550] CGAGGTGCCTCTGGACATCTGCACCTCCATCTGTAAGTACCCCGATTATATCAAG
[0551] ATGGTGTCCGAGCCTTACGGCGACTCTCTGTTCTTTTATCTGCGGAGAGAGCAGA
[0552] TGTTCGTGAGGCACCTGTTTAATAGGGCAGGAGCAGTGGGAGAGAACGTGCCAG
[0553] ACGATCTGTACATCAAGGGCTCCGGCTCTACCGCCAATCTGGCCAGCTCCAACTA
[0554] TTTCCCTACCCCAAGCGGCTCCATGGTGACAAGCGATGCCCAGATCTTTAACAAG
[0555] CCATACTGGCTGCAGAGGGCACAGGGACACAATAACGGCATCTGCTGGGGCAAT
[0556] CAGCTGTTCGTGACCGTGGTGGACACCACACGCTCTACAAACATGAGCCTGTGCG
[0557] CCGCCATCTCTACCAGCGAGACCACATACAAGAACACAAACTTTAAGGAGTACC
[0558] TGCGGCACGGCGAGGAGTATGACCTGCAGTTCATCTTTCAGCTGTGCAAGATCAC
[0559] CCTGACAGCCGATGTGATGACCTACATCCACTCCATGAACAGCACAATCCTGGAG
[0560] GACTGGAACTTCGGACTGCAGCCACCTCCAGGAGGCACCCTGATCCCAGTGCTG
[0561] GACGAGAATGGCCTGTTCGCCCCCGAGGATACCTATAGGTTTGTGACAAGCCAG
[0562] GCCATCGCATGTCAGAAGCACACCCCACCTGCACCAAAGGAGGACCCCCTGAAG
[0563] AAGTACACATTCTGGGAGGTGAACCTGAAGGAGAAGTTTTCCGCCGACCTGGAT
[0564] CAGTTCCCACTGGGACGGAAGTTTCTGCTGCAGGCAGGCCTGAAGGCAAAGCCA
[0565] AAGTTTACCCTGGGCAAGAGAAAGGCCACCCCTACCACATCTAGCACATCCACC
[0566] ACAGCCAAGCGGAAGAAGAGAAAGCTGTGA
[0567] 14. SEQ ID NO: 14 - L1:2C7 h4_i Generation II - amino acid
[0568] MSLWLPSEATVYLPPVPVSKVVSTDEYVARTNIYYHAGTSRLLAVGHPYFPIKKPNN
[0569] NKILVPKVSGLQYRVFRIHLPDPNKFGFPDTSFYNPDTQRLVWACVGVEVGRGQPLG
[0570] VGISGHPLLNKLDDTENASAYAANAGVDNRECISMDYKQTQLCLIGCKPPIGEHWG
[0571] KGSPCTNVAVNPGDCPPLELINTVIQDGDMVDTGFGAMDFTTLQANKSEVPLDICTSI
[0572] CKYPDYIKMVSEPYGDSLFFYLRREQMFVRHLFNRAGAVGENVPDDLYIKGSGSTA
[0573] NLASSNYFPTPSGSMVTSDAQIFNKPYWLQRAQGHNNGICWGNQLFVTVVDTTRST
[0574] NMSLCAAISTSETTYKNTNFKEYLRHGEEYDLQFIFQLCKITLTADVMTYIHSMNSTI
[0575] LEDWNFGLQPPPGGTLIPVLDENGLFAPEDTYRFVTSQAIACQKHTPPAPKEDPLKKY
[0576] TFWEVNLKEKFSADLDQFPLGRKFLLQAGLKAKPKFTLGKRKATPTTSSTSTTAKRK
[0577] KRKL* 15. SEQ ID NO: 15 - L1:2C7 h4_s Generation II - nucleic acid
[0578] ATGAGCCTGTGGCTGCCTTCCGAGGCCACAGTGTACCTGCCCCCTGTGCCAGTGA
[0579] GCAAGGTGGTGTCCACCGATGAGTATGTGGCCCGGACAAATATCTACTATCACGC
[0580] AGGCACCTCTAGACTGCTGGCAGTGGGCCACCCCTACTTCCCTATCAAGAAGCCC
[0581] AACAATAACAAGATCCTGGTGCCTAAGGTGTCTGGCCTGCAGTATAGGGTGTTCC
[0582] GCATCCACCTGCCAGACCCCAATAAGTTCGGCTTTCCTGACACCAGCTTTTACAA
[0583] CCCAGATACACAGAGGCTGGTGTGGGCATGCGTGGGAGTGGAAGTGGGAAGGG
[0584] GCCAGCCTCTGGGAGTGGGAATCTCTGGACACCCACTGCTGAATAAGCTGGACG
[0585] ATACCGAGAACGCCAGCGCCTACGCAGCAAATGCAGGAGTGGACAACAGGGAG
[0586] TGTATCTCCATGGATTATAAGCAGACACAGCTGTGCCTGATCGGCTGTAAGCCAC
[0587] CAATCGGAGAGCACTGGGGCAAGGGATCCCCATGCACCAATGTGGCCGTGAACC
[0588] CCGGCGATTGTCCTCCACTGGAGCTGATCAATACCGTGATCCAGGACGGCGATAT
[0589] GGTGGACACAGGCTTCGGCGCCATGGACTTCACCACCCTGCAGGCCAACAAGAG
[0590] CGAGGTGCCTCTGGACATCTGCACCTCCATCTGTAAGTACCCCGATTATATCAAG
[0591] ATGGTGTCCGAGCCTTACGGCGACTCTCTGTTCTTTTATCTGCGGAGAGAGCAGA
[0592] TGTTCGTGAGGCACCTGTTTAATAGGGCAGGAGCAGTGGGAGAGAACGTGCCAG
[0593] ACGATCTGTACATCAAGGGCTCCGGCTCTACCGCCAATCTGGCCAGCTCCAACTA
[0594] TTTCCCTACCCCAAGCGGCTCCATGGTGACAAGCGATGCCCAGATCTTTAACAAG
[0595] CCCTATTGGCTGCAGAGGGCCCAGGGCCACAATAACGGCATCTGCTGGGGCAAT
[0596] CAGCTGTTCGTGACCGTGGTGGACACCACACGCTCTACAAACATGAGCCTGTGCG
[0597] CCGCCATCTCTACCAGCGAGACCACATACAAGAACACAAACTTTAAGGAGTACC
[0598] TGAGGCACGGCGAGGAGTATGACCTGCAGTTCATCTTTCAGCTGTGCAAGATCAC
[0599] CCTGACAGCCGATGTGATGACCTACATCCACTCCATGAACAGCACAATCCTGGAG
[0600] GACTGGAACTTCGGACTGCAGCCACCTCCAGGAGGAACCATCCCAGTGCTGGAT
[0601] GAGAATGGACTGTTTGCACCAACACCACCTGCACCAAAGGAGGACCCCCTGAAG
[0602] AAGTACACCTTCTGGGAGGTGAACCTGAAGGAGAAGTTTTCCGCCGACCTGGAT
[0603] CAGTTCCCACTGGGACGGAAGTTTCTGCTGCAGGCAGGCCTGAAGGCAAAGCCA
[0604] AAGTTCACCCTGGGCAAGAGAAAGGCCACCCCTACCACATCTAGCACAAGCACC
[0605] ACAGCCAA GCGGAAGAAGAGAAAGCTGTGA
[0606] 16. SEQ ID NO: 16 - L1:2C7 h4_s Generation II - amino acid
[0607] MSLWLPSEATVYLPPVPVSKVVSTDEYVARTNIYYHAGTSRLLAVGHPYFPIKKPNN
[0608] NKILVPKVSGLQYRVFRIHLPDPNKFGFPDTSFYNPDTQRLVWACVGVEVGRGQPLG VGISGHPLLNKLDDTENASAYAANAGVDNRECISMDYKQTQLCLIGCKPPIGEHWG
[0609] KGSPCTNVAVNPGDCPPLELINTVIQDGDMVDTGFGAMDFTTLQANKSEVPLDICTSI
[0610] CKYPDYIKMVSEPYGDSLFFYLRREQMFVRHLFNRAGAVGENVPDDLYIKGSGSTA
[0611] NLASSNYFPTPSGSMVTSDAQIFNKPYWLQRAQGHNNGICWGNQLFVTVVDTTRST
[0612] NMSLCAAISTSETTYKNTNFKEYLRHGEEYDLQFIFQLCKITLTADVMTYIHSMNSTI
[0613] LEDWNFGLQPPPGGTIPVLDENGLFAPTPPAPKEDPLKKYTFWEVNLKEKFSADLDQ
[0614] FPLGRKFLLQAGLKAKPKFTLGKRKATPTTSSTSTTAKRKKRKL*
[0615] 17. SEQ ID NO: 17 - pTRAkc-rbcsl-cTP
[0616] AATTCCGCCCCTAGAAATATTTGCGACTCTTCTGGCATGTAATATTTCGTTAAATA
[0617] TGAAGTGCTCCATTTTTATTAACTTTAAATAATTGGTTGTACGATCACTTTCTTAT
[0618] CAAGCGTTACTAAAATGCGTCAATCTCTTTGTTCTTCCATATTCATATGTCAAAAT
[0619] CTATCAAAATTCTTATATATCTTTTTCGAATTTGAAGTGAAATTTCGATAATTTAA
[0620] AATTAAATAGAACATATCATTATTTAGGTGTCATATTGATTTTTATACTTAATTAC
[0621] TAAATTTGGTTAACTTTGAAAGTGTACATCAACGAAAAATTAGTCAAACGACTAA
[0622] AATAAATAAATATCATGTGTTATTAAGAAAATTCTCCTATAAGAATATTTTAATA
[0623] GATCATATGTTTGTAAAAAAAATTAATTTTTACTAACACATATATTTACTTATCAA
[0624] AAATTTGACAAAGTAAGATTAAAATAATATTCATCTAACAAAAAAAAACCAGAA
[0625] AATGCTGAAAACCCGGCAAAACCGAACCAATCCAAACCGATATAGTTGGTTTGG
[0626] TTTGATTTTGATATAAACCGAACCAACTCGGTCCATTTGCACCCCTAATCATAAT
[0627] AGCTTTAATATTTCAAGATATTATTAAGTTAACGTTGTCAATATCCTGGAAATTTT
[0628] GCAAAATGAATCAAGCCTATATGGCTGTAATATGAATTTAAAAGCAGCTCGATGT
[0629] GGTGGTAATATGTAATTTACTTGATTCTAAAAAAATATCCCAAGTATTAATAATT
[0630] TCTGCTAGGAAGAAGGTTAGCTACGATTTACAGCAAAGCCAGAATACAAAGAAC
[0631] CATAAAGTGATTGAAGCTCGAAATATACGAAGGAACAAATATTTTTAAAAAAAT
[0632] ACGCAATGACTTGGAACAAAAGAAAGTGATATATTTTTTGTTCTTAAACAAGCAT
[0633] CCCCTCTAAAGAATGGCAGTTTTCCTTTGCATGTAACTATTATGCTCCCTTCGTTA
[0634] CAAAAATTTTGGACTACTATTGGGCGCGGGGCGCGCCCGGTCCAAAGACCAGAG
[0635] GGCTATTGAGACTTTTCAACAAAGGGTAATATCGGGAAACCTCCTCGGATTCCAT
[0636] TGCCCAGCTATCTGTCACTTCATCGAAAGGACAGTAGAAAAGGAAGATGGCTTCT
[0637] ACAAATGCCATCATTGCGATAAAGGAAAGGCTATCGTTCAAGATGCCTCTACCG
[0638] ACAGTGGTCCCAAAGATGGACCCCCACCCACGAGGAACATCGTGGAAAAAGAAG
[0639] ACGTTCCAACCACGTCTTCAAAGCAAGTGGATTGATGTGATACATGGTGGAGCAC GACACTCTCGTCTACTCCAAGAATATCAAAGATACAGTCTCAGAAGACCAGAGG
[0640] GCTATTGAGACTTTTCAACAAAGGGTAATATCGGGAAACCTCCTCGGATTCCATT
[0641] GCCCAGCTATCTGTCACTTCATCGAAAGGACAGTAGAAAAGGAAGATGGCTTCT
[0642] ACAAATGCCATCATTGCGATAAAGGAAAGGCTATCGTTCAAGATGCCTCTACCG
[0643] ACAGTGGTCCCAAAGATGGACCCCCACCCACGAGGAACATCGTGGAAAAAGAAG
[0644] ACGTTCCAACCACGTCTTCAAAGCAAGTGGATTGATGTGATATCTCCACTGACGT
[0645] AAGGGATGACGCACAATCCCACTATCCTTCGCAAGACCCTTCCTCTATATAAGGA
[0646] AGTTCATTTCATTTGGAGAGGACACGCTGAATTCACAACACAAATCAGATTTATA
[0647] GAGAGATTTATAAAAAAAAAAAAAACAATGGCTTCCTCTGTTATTTCCTCTGCAG
[0648] CTGTTGCTACACGCACCAATGTTACACAAGCTGGCAGCATGATTGCACCTTTCAC
[0649] TGGTCTCAAATCTGCTGCTACTTTCCCTGTTTCAAGGAAGCAAAACCTTGACATC
[0650] ACTTCCATTGCTAGCAATGGTGGACGCGTTAGGTGCATGCCCGCTCGAGCTCGGA
[0651] TCCTCTAGAGTCCGCAAAAATCACCAGTCTCTCTCTACAAATCTATCTCTCTCTAT
[0652] TTTTCTCCAGAATAATGTGTGAGTAGTTCCCAGATAAGGGAATTAGGGTTCTTAT
[0653] AGGGTTTCGCTCATGTGTTGAGCATATAAGAAACCCTTAGTATGTATTTGTATTTG
[0654] TAAAATACTTCTATCAATAAAATTTCTAATTCCTAAAACCAAAATCCAGTGACCG
[0655] GGCGGCCGGCCGCCCCTAGAAATATTTGCGACTCTTCTGGCATGTAATATTTCGT
[0656] TAAATATGAAGTGCTCCATTTTTATTAACTTTAAATAATTGGTTGTACGATCACTT
[0657] TCTTATCAAGCGTTACTAAAATGCGTCAATCTCTTTGTTCTTCCATATTCATATGT
[0658] CAAAATCTATCAAAATTCTTATATATCTTTTTCGAATTTGAAGTGAAATTTCGATA
[0659] ATTTAAAATTAAATAGAACATATCATTATTTAGGTGTCATATTGATTTTTATACTT
[0660] AATTACTAAATTTGGTTAACTTTGAAAGTGTACATCAACGAAAAATTAGTCAAAC
[0661] GACTAAAATAAATAAATATCATGTGTTATTAAGAAAATTCTCCTATAAGAATATT
[0662] TTAATAGATCATATGTTTGTAAAAAAAATTAATTTTTACTAACACATATATTTACT
[0663] TATCAAAAATTTGACAAAGTAAGATTAAAATAATATTCATCTAACAAAAAAAAA
[0664] CCAGAAAATGCTGAAAACCCGGCAAAACCGAACCAATCCAAACCGATATAGTTG
[0665] GTTTGGTTTGATTTTGATATAAACCGAACCAACTCGGTCCATTTGCACCCCTAATC
[0666] ATAATAGCTTTAATATTTCAAGATATTATTAAGTTAACGTTGTCAATATCCTGGA
[0667] AATTTTGCAAAATGAATCAAGCCTATATGGCTGTAATATGAATTTAAAAGCAGCT
[0668] CGATGTGGTGGTAATATGTAATTTACTTGATTCTAAAAAAATATCCCAAGTATTA
[0669] ATAATTTCTGCTAGGAAGAAGGTTAGCTACGATTTACAGCAAAGCCAGAATACA
[0670] AAGAACCATAAAGTGATTGAAGCTCGAAATATACGAAGGAACAAATATTTTTAA
[0671] AAAAATACGCAATGACTTGGAACAAAAGAAAGTGATATATTTTTTGTTCTTAAAC AAGCATCCCCTCTAAAGAATGGCAGTTTTCCTTTGCATGTAACTATTATGCTCCCT
[0672] TCGTTACAAAAATTTTGGACTACTATTGGGCGGGTGGAGGGGGATCAGATTGTCG
[0673] TTTCCCGCCTTCAGTTTAAACTATCAGTGTTTGACAGGATATATTGGCGGGTAAA
[0674] CCTAAGAGAAAAGAGCGTTTATTAGAATAATCGGATATTTAAAAGGGCGTGAAA
[0675] AGGTTTATCCGTTCGTCCATTTGTATGTGTACATCACCGACGAGCAAGGCAAGAC
[0676] CGAGCGCCTTTCCGACGCTCACCGGGCTGGTTGCCCTCGCCGCTGGGCTGGCGGC
[0677] CGTCTATGGCCCTGCAAACGCGCCAGAAACGCCGTCGAAGCCGTGTGCGAGACA
[0678] CCGGCCGCCGGCGTTGTGGATACCTCGCGGAAAACTTGGCCCTCACTGACAGATG
[0679] AGGGGCGGACGTTGACACTTGAGGGGCCGACTCACCCGGCGCGGCGTTGACAGA
[0680] TGAGGGGCAGGCTCGATTTCGGCCGGCGACGTGGAGCTGGCCAGCCTCGCAAAT
[0681] CGGCGAAAACGCCTGATTTTACGCGAGTTTCCCACAGATGATGTGGACAAGCCTG
[0682] GGGATAAGTGCCCTGCGGTATTGACACTTGAGGGGCGCGACTACTGACAGATGA
[0683] GGGGCGCGATCCTTGACACTTGAGGGGCAGAGTGCTGACAGATGAGGGGCGCAC
[0684] CTATTGACATTTGAGGGGCTGTCCACAGGCAGAAAATCCAGCATTTGCAAGGGTT
[0685] TCCGCCCGTTTTTCGGCCACCGCTAACCTGTCTTTTAACCTGCTTTTAAACCAATA
[0686] TTTATAAACCTTGTTTTTAACCAGGGCTGCGCCCTGTGCGCGTGACCGCGCACGC
[0687] CGAAGGGGGGTGCCCCCCCTTCTCGAACCCTCCCGGCCCGCTAACGCGGGCCTCC
[0688] CATCCCCCCAGGGGCTGCGCCCCTCGGCCGCGAACGGCCTCACCCCAAAAATGG
[0689] CAGCGCTGGCAGTCCTTGCCATTGCCGGGATCGGGGCAGTAACGGGATGGGCGA
[0690] TCAGCCCGACAAGCTACCCCTATTTGTTTATTTTTCTAAATACATTCAAATATGTA
[0691] TCCGCTCATGAGACAATAACCCTGATAAATGCTTCAATAATATTGAAAAAGGAA
[0692] GAGTATGAGTATTCAACATTTCCGTGTCGCCCTTATTCCCTTTTTTGCGGCATTTT
[0693] GCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTAAAAGATGCTGAAGA
[0694] TCAGTTGGGTGCACGAGTGGGTTACATCGAACTGGATCTCAACAGCGGTAAGAT
[0695] CCTTGAGAGTTTTCGCCCCGAAGAACGTTTTCCAATGATGAGCACTTTTAAAGTT
[0696] CTGCTATGTGGCGCGGTATTATCCCGTATTGACGCCGGGCAAGAGCAACTCGGTC
[0697] GCCGCATACACTATTCTCAGAATGACTTGGTTGAGTACTCACCAGTCACAGAAAA
[0698] GCATCTTACGGATGGCATGACAGTAAGAGAATTATGCAGTGCTGCCATAACCAT
[0699] GAGTGATAACACTGCGGCCAACTTACTTCTGACAACGATCGGAGGACCGAAGGA
[0700] GCTAACCGCTTTTTTGCACAACATGGGGGATCATGTAACTCGCCTTGATCGTTGG
[0701] GAACCGGAGCTGAATGAAGCCATACCAAACGACGAGCGTGACACCACGATGCCT
[0702] GTAGCAATGGCAACAACGTTGCGCAAACTATTAACTGGCGAACTACTTACTCTAG
[0703] CTTCCCGGCAACAATTAATAGACTGGATGGAGGCGGATAAAGTTGCAGGACCAC TTCTGCGCTCGGCCCTTCCGGCTGGCTGGTTTATTGCTGATAAATCTGGAGCCGGT
[0704] GAGCGTGGGTCTCGCGGTATCATTGCAGCACTGGGGCCAGATGGTAAGCCCTCCC
[0705] GTATCGTAGTTATCTACACGACGGGGAGTCAGGCAACTATGGATGAACGAAATA
[0706] GACAGATCGCTGAGATAGGTGCCTCACTGATTAAGCATTGGTAACTGTCAGACCA
[0707] AGTTTACTCATATATACTTTAGATTGATTTAAAACTTCATTTTTAATTTAAAAGGA
[0708] TCTAGGTGAAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTT
[0709] TCGTTCCACTGAGCGTCAGACCCCGTAGAAAAGATCAAAGGATCTTCTTGAGATC
[0710] CTTTTTTTCTGCGCGTAATCTGCTGCTTGCAAACAAAAAAACCACCGCTACCAGC
[0711] GGTGGTTTGTTTGCCGGATCAAGAGCTACCAACTCTTTTTCCGAAGGTAACTGGC
[0712] TTCAGCAGAGCGCAGATACCAAATACTGTCCTTCTAGTGTAGCCGTAGTTAGGCC
[0713] ACCACTTCAAGAACTCTGTAGCACCGCCTACATACCTCGCTCTGCTAATCCTGTT
[0714] ACCAGTGGCTGCTGCCAGTGGCGATAAGTCGTGTCTTACCGGGTTGGACTCAAGA
[0715] CGATAGTTACCGGATAAGGCGCAGCGGTCGGGCTGAACGGGGGGTTCGTGCACA
[0716] CAGCCCAGCTTGGAGCGAACGACCTACACCGAACTGAGATACCTACAGCGTGAG
[0717] CTATGAGAAAGCGCCACGCTTCCCGAAGGGAGAAAGGCGGACAGGTATCCGGTA
[0718] AGCGGCAGGGTCGGAACAGGAGAGCGCACGAGGGAGCTTCCAGGGGGAAACGC
[0719] CTGGTATCTTTATAGTCCTGTCGGGTTTCGCCACCTCTGACTTGAGCGTCGATTTT
[0720] TGTGATGCTCGTCAGGGGGGCGGAGCCTATGGAAAAACGCCAGCAACGCGGCCT
[0721] TTTTACGGTTCCTGGCCTTTTGCTGGCCTTTTGCTCACATGGACTCTAGCTAGAGG
[0722] ATCACAGGCAGCAACGCTCTGTCATCGTTACAATCAACATGCTACCCTCCGCGAG
[0723] ATCATCCGTGTTTCAAACCCGGCAGCTTAGTTGCCGTTCTTCCGAATAGCATCGG
[0724] TAACATGAGCAAAGTCTGCCGCCTTACAACGGCTCTCCCGCTGACGCCGTCCCGG
[0725] ACTGATGGGCTGCCTGTATCGAGTGGTGATTTTGTGCCGAGCTGCCGGTCGGGGA
[0726] GCTGTTGGCTGGCTGGTGGCAGGATATATTGTGGTGTAAACAAATTGACGCTTAG
[0727] ACAACTTAATAACACATTGCGGACGTTTTTAATGATCGAATACTAACGTCTCTAC
[0728] CAGATATCAGCTTGCATGCCGGTCGATCTAGTAACATAGATGACACCGCGCGCG
[0729] ATAATTTATCCTAGTTTGCGCGCTATATTTTGTTTTCTATCGCGTATTAAATGTAT
[0730] AATTGCGGGACTCTAATCATAAAAACCCATCTCATAAATAACGTCATGCATTACA
[0731] TGTTAATTATTACATGCTTAACGTAATTCAACAGAAATTATATGATAATCATCGC
[0732] AAGACCGGCAACAGGATTCAATCTTAAGAAACTTTATTGCCAAATGTTTGAACGA
[0733] TCTGCTTGACTCTAGCTAGAGTCCGAACCCCAGAGTCCCGCTCAGAAGAACTCGT
[0734] CAAGAAGGCGATAGAAGGCGATGCGCTGCGAATCGGGAGCGGCGATACCGTAA
[0735] AGCACGAGGAAGCGGTCAGCCCATTCGCCGCCAAGCTCTTCAGCAATATCACGG GTAGCCAACGCTATGTCCTGATAGCGGTCCGCCACACCCAGCCGGCCACAGTCG
[0736] ATGAATCCAGAAAAGCGGCCATTTTCCACCATGATATTCGGCAAGCAGGCATCG
[0737] CCGTGGGTCACGACGAGATCCTCGCCGTCGGGCATCCGCGCCTTGAGCCTGGCGA
[0738] ACAGTTCGGCTGGCGCGAGCCCCTGATGCTCTTCGTCCAGATCATCCTGATCGAC
[0739] AAGACCGGCTTCCATCCGAGTACGTGCTCGCTCGATGCGATGTTTCGCTTGGTGG
[0740] TCGAATGGGCAGGTAGCCGGATCAAGCGTATGCAGCCGCCGCATTGCATCAGCC
[0741] ATGATGGATACTTTCTCGGCAGGAGCAAGGTGAGATGACAGGAGATCCTGCCCC
[0742] GGCACTTCGCCCAATAGCAGCCAGTTCCTTCCCGCTTCAGTGACAACGTCGAGCA
[0743] CAGCTGCGCAAGGAACGCCCGTTGTGGCCAGCCACGATAGCCGCGCTGCCTCGT
[0744] CTTGGAGTTCATTCAGGGCACCGGACAGGTCGGTCTTGACAAAAAGAACCGGGC
[0745] GCCCCTGCGCTGACAGCCGGAACACGGCGGCATCAGAGCAGCCGATTGTTTGTT
[0746] GTGCCCAGTCATAGCCGAATAGCCTCTCCACCCAAGCGGCCGGAGAACCTGCGT
[0747] GCAATCCATCTTGTTCAATCATGCCTGCATCGAGTTGAGAGTGAATATGAGACTC
[0748] TAATTGGATACCGAGGGGAATTTATGGAACGTCAGTGGAGCATTTTTGACAAGA
[0749] AATATTTGCTAGCTGATAGTGACCTTAGGCGACTTTTGAACGCGCAATAATGGTT
[0750] TCTGACGTATGTGCTTAGCTCATTAAACTCCAGAAACCCGCGGCTCAGTGGCTCC
[0751] TTCAACGTTGCGGTTCTGTCAGTTCCAAACGTAAAACGGCTTGTCCCGCGTCATC
[0752] GGCGGGGGTCATAACGTGACTCCCTTAATTCTCCGCTCATGATCGATATCCATTG AAGAGCAAGCT
[0753] 18. SEQ ID NO: 18 - pRIC3
[0754] GAAGAGCGTGACTCCGAGGGGTTGCCTCAAACTCTATCTTATAACCGGCGTGGA
[0755] GGCATGGAGGCAGGGGTATTTTGGTCATTTTAATAGATAGTGGAAAATGACGTG
[0756] GAATTTACTTAAAGACGAAGTCTTTGCGACAAGGGGGGGCCCACGCCGAATTTA
[0757] ATATTACCGGCGTGGCCCCCCCTTATCGCGAGTGCTTTAGCACGAGCGGTCCAGA
[0758] TTTAAAGTAGAAAATTTCCCGCCCACTAGGGTTAAAGGTGTTCACACTATAAAAG
[0759] CATATACGATGTGATGGTATTTGCTCGACCTGGTCCAAAGACCAGAGGGCTATTG
[0760] AGACTTTTCAACAAAGGGTAATATCGGGAAACCTCCTCGGATTCCATTGCCCAGC
[0761] TATCTGTCACTTCATCGAAAGGACAGTAGAAAAGGAAGATGGCTTCTACAAATG
[0762] CCATCATTGCGATAAAGGAAAGGCTATCGTTCAAGATGCCTCTACCGACAGTGGT
[0763] CCCAAAGATGGACCCCCACCCACGAGGAACATCGTGGAAAAAGAAGACGTTCCA
[0764] ACCACGTCTTCAAAGCAAGTGGATTGATGTGATACATGGTGGAGCACGACACTCT
[0765] CGTCTACTCCAAGAATATCAAAGATACAGTCTCAGAAGACCAGAGGGCTATTGA GACTTTTCAACAAAGGGTAATATCGGGAAACCTCCTCGGATTCCATTGCCCAGCT
[0766] ATCTGTCACTTCATCGAAAGGACAGTAGAAAAGGAAGATGGCTTCTACAAATGC
[0767] CATCATTGCGATAAAGGAAAGGCTATCGTTCAAGATGCCTCTACCGACAGTGGTC
[0768] CCAAAGATGGACCCCCACCCACGAGGAACATCGTGGAAAAAGAAGACGTTCCAA
[0769] CCACGTCTTCAAAGCAAGTGGATTGATGTGATATCTCCACTGACGTAAGGGATGA
[0770] CGCACAATCCCACTATCCTTCGCAAGACCCTTCCTCTATATAAGGAAGTTCATTTC
[0771] ATTTGGAGAGGACACGCTGAGTTCACAACACAAATCAGATTTATAGAGAGATTT
[0772] ATAAAAAAAAAAAAACATGTGATCCCGGGAATTCGCTAGCACTAGTAAGCTTGT
[0773] CGACTCGAGCTCTCTAGAGTCCGCAAAAATCACCAGTCTCTCTCTACAAATCTAT
[0774] CTCTCTCTATTTTTCTCCAGAATAATGTGTGAGTAGTTCCCAGATAAGGGAATTA
[0775] GGGTTCTTATAGGGTTTCGCTCATGTGTTGAGCATATAAGAAACCCTTAGTATGT
[0776] ATTTGTATTTGTAAAATACTTCTATCAATAAAATTTCTAATTCCTAAAACCAAAAT
[0777] CCAGTGACCGGGCGGCGGGTCGAGAATGATTATTTTATGAATATATTTCATTGTG
[0778] CAAGTAGATAGAAATTACATATGTTACATAACACACGAAATAAACAAAAAAAGA
[0779] CAATCCAAAAACAAACACCCCAAAAAAAATAATCACTTTAGATAAACTCGTATG
[0780] AGGAGAGGCACGTTCAGTGACTCGACGATTCCCGAGCAAAAAAAGTCTCCCCGT
[0781] CACACATATAGTGGGTGACGCAATTATCTTTAAAGTAATCCTTCTGTTGACTTGTC
[0782] ATTGATAACATCCAGTCTTCGTCAGGATTGCAAAGAATTATAGAAGGGATCCCAC
[0783] CTTTTATTTTCTTCTTTTTTCCATATTTAGGGTTGACAGTGAAATCAGACTGGCAA
[0784] CCTATTAATTGCTTCCACAATGGGACGAACTTGAAGGGGATGTCGTCGATGATAT
[0785] TATAGGTGGCGTGTTCATCGTAGTTGGTGAAATCGATGGTACCGTTCCAATAGTT
[0786] GTGTCGTCCGAGACTTCTAGCCCAGGTGGTCTTTCCGGTACGAGTTGGTCCGCAG
[0787] ATGTAGAGGCTGGGGTGTCGGATTCCATTCCTTCCATTGTCCTGGTTAAATCGGC
[0788] CATCCATTCAAGGTCAGATTGAGCTTGTTGGTATGAGACAGGATGTATGTAAGTA
[0789] TAAGCGTCTATGCTTACATGGTATAGATGGGTTTCCCTCCAGGAGTGTAGATCTT
[0790] CGTGGCAGCGAAGATCTGATTCTGTGAAGGGCGACACATACGGTTCAGGTTGTG
[0791] GAGGGAATAATTTGTTGGCTGAATATTCCAGCCATTGAAGTTTTGTTGCCCATTC
[0792] ATGAGGGAATTCTTCCTTGATCATGTCAAGATATTCCTCCTTAGACGTTGCAGTCT
[0793] GGATAATAGTTCTCCATCGTGCGTCAGATTTGCGAGGAGAGACCTTATGATCTCG
[0794] GAAATCTCCTCTGGTTTTAATATCTCCGTCCTTTGATATGTAATCAAGGACTTGTT
[0795] TAGAGTTTCTAGCTGGCTGGATATTAGGGTGATTTCCTTCAAAATCGAAAAAAGA
[0796] AGGATCCCTAATACAAGGTTTTTTATCAAGCTGGAGAAGAGCATGATAGTGGGT
[0797] AGTGCCATCTTGATGAAGCTCAGAAGCAACACCAAGGAAGAAAATAAGAAAAG GTGTGAGTTTCTCCCAGAGAAACTGGAATAAATCATCTCTTTGAGATGAGCACTT
[0798] GGGATAGGTAAGGAAAACATATTTAGATTGGAGTCTGAAGTTCTTACTAGCAGA
[0799] AGGCATGTTGTTGTGACTCCGAGGGGTTGCCTCAAACTCTATCTTATAACCGGCG
[0800] TGGAGGCATGGAGGCAGGGGTATTTTGGTCATTTTAATAGATAGTGGAAAATGA
[0801] CGTGGAATTTACTTAAAGACGAAGTCTTTGCGACAAGGGGGGGCCCACGCCGAA
[0802] TTTAATATTACCGGCGTGGCCCCCCCTTATCGCGAGTGCTTTAGCACGAGCGGTC
[0803] CAGATTTAAAGTAGAAAATTTCCCGCCCACTAGGGTTAAAGGTGTTCACACTATA
[0804] CAAGCATATACGATGTGATGGTATTGACTAGAGTTTAAACTATCAGTGTTTGACA
[0805] GGATATATTGGCGGGTAAACCTAAGAGAAAAGAGCGTTTATTAGAATAATCGGA
[0806] TATTTAAAAGGGCGTGAAAAGGTTTATCCGTTCGTCCATTTGTATGTGTACATCA
[0807] CCGACGAGCAAGGCAAGACCGAGCGCCTTTCCGACGCTCACCGGGCTGGTTGCC
[0808] CTCGCCGCTGGGCTGGCGGCCGTCTATGGCCCTGCAAACGCGCCAGAAACGCCG
[0809] TCGAAGCCGTGTGCGAGACACCGGCCGCCGGCGTTGTGGATACCTCGCGGAAAA
[0810] CTTGGCCCTCACTGACAGATGAGGGGCGGACGTTGACACTTGAGGGGCCGACTC
[0811] ACCCGGCGCGGCGTTGACAGATGAGGGGCAGGCTCGATTTCGGCCGGCGACGTG
[0812] GAGCTGGCCAGCCTCGCAAATCGGCGAAAACGCCTGATTTTACGCGAGTTTCCCA
[0813] CAGATGATGTGGACAAGCCTGGGGATAAGTGCCCTGCGGTATTGACACTTGAGG
[0814] GGCGCGACTACTGACAGATGAGGGGCGCGATCCTTGACACTTGAGGGGCAGAGT
[0815] GCTGACAGATGAGGGGCGCACCTATTGACATTTGAGGGGCTGTCCACAGGCAGA
[0816] AAATCCAGCATTTGCAAGGGTTTCCGCCCGTTTTTCGGCCACCGCTAACCTGTCTT
[0817] TTAACCTGCTTTTAAACCAATATTTATAAACCTTGTTTTTAACCAGGGCTGCGCCC
[0818] TGTGCGCGTGACCGCGCACGCCGAAGGGGGGTGCCCCCCCTTCTCGAACCCTCCC
[0819] GGCCCGCTAACGCGGGCCTCCCATCCCCCCAGGGGCTGCGCCCCTCGGCCGCGA
[0820] ACGGCCTCACCCCAAAAATGGCAGCGCTGGCAGTCCTTGCCATTGCCGGGATCG
[0821] GGGCAGTAACGGGATGGGCGATCAGCCCGAAAGCTACCCCTATTTGTTTATTTTT
[0822] CTAAATACATTCAAATATGTATCCGCTCATGAGACAATAACCCTGATAAATGCTT
[0823] CAATAATATTGAAAAAGGAAGAGTATGAGTATTCAACATTTCCGTGTCGCCCTTA
[0824] TTCCCTTTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGTG
[0825] AAAGTAAAAGATGCTGAAGATCAGTTGGGTGCACGAGTGGGTTACATCGAACTG
[0826] GATCTCAACAGCGGTAAGATCCTTGAGAGTTTTCGCCCCGAAGAACGTTTTCCAA
[0827] TGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTATTATCCCGTATTGACGC
[0828] CGGGCAAGAGCAACTCGGTCGCCGCATACACTATTCTCAGAATGACTTGGTTGAG
[0829] TACTCACCAGTCACAGAAAAGCATCTTACGGATGGCATGACAGTAAGAGAATTA TGCAGTGCTGCCATAACCATGAGTGATAACACTGCGGCCAACTTACTTCTGACAA
[0830] CGATCGGAGGACCGAAGGAGCTAACCGCTTTTTTGCACAACATGGGGGATCATG
[0831] TAACTCGCCTTGATCGTTGGGAACCGGAGCTGAATGAAGCCATACCAAACGACG
[0832] AGCGTGACACCACGATGCCTGTAGCAATGGCAACAACGTTGCGCAAACTATTAA
[0833] CTGGCGAACTACTTACTCTAGCTTCCCGGCAACAATTAATAGACTGGATGGAGGC
[0834] GGATAAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTCCGGCTGGCTGGTTTATT
[0835] GCTGATAAATCTGGAGCCGGTGAGCGTGGGTCTCGCGGTATCATTGCAGCACTGG
[0836] GGCCAGATGGTAAGCCCTCCCGTATCGTAGTTATCTACACGACGGGGAGTCAGG
[0837] CAACTATGGATGAACGAAATAGACAGATCGCTGAGATAGGTGCCTCACTGATTA
[0838] AGCATTGGTAACTGTCAGACCAAGTTTACTCATATATACTTTAGATTGATTTAAA
[0839] ACTTCATTTTTAATTTAAAAGGATCTAGGTGAAGATCCTTTTTGATAATCTCATGA
[0840] CCAAAATCCCTTAACGTGAGTTTTCGTTCCACTGAGCGTCAGACCCCGTAGAAAA
[0841] GATCAAAGGATCTTCTTGAGATCCTTTTTTTCTGCGCGTAATCTGCTGCTTGCAAA
[0842] CAAAAAAACCACCGCTACCAGCGGTGGTTTGTTTGCCGGATCAAGAGCTACCAA
[0843] CTCTTTTTCCGAAGGTAACTGGCTTCAGCAGAGCGCAGATACCAAATACTGTTCT
[0844] TCTAGTGTAGCCGTAGTTAGGCCACCACTTCAAGAACTCTGTAGCACCGCCTACA
[0845] TACCTCGCTCTGCTAATCCTGTTACCAGTGGCTGCTGCCAGTGGCGATAAGTCGT
[0846] GTCTTACCGGGTTGGACTCAAGACGATAGTTACCGGATAAGGCGCAGCGGTCGG
[0847] GCTGAACGGGGGGTTCGTGCACACAGCCCAGCTTGGAGCGAACGACCTACACCG
[0848] AACTGAGATACCTACAGCGTGAGCTATGAGAAAGCGCCACGCTTCCCGAAGGGA
[0849] GAAAGGCGGACAGGTATCCGGTAAGCGGCAGGGTCGGAACAGGAGAGCGCACG
[0850] AGGGAGCTTCCAGGGGGAAACGCCTGGTATCTTTATAGTCCTGTCGGGTTTCGCC
[0851] ACCTCTGACTTGAGCGTCGATTTTTGTGATGCTCGTCAGGGGGGCGGAGCCTATG
[0852] GAAAAACGCCAGCAACGCGGCCTTTTTACGGTTCCTGGCCTTTTGCTGGCCTTTT
[0853] GCTCACATGGACTCTAGCTAGAGGATCACAGGCAGCAACGCTCTGTCATCGTTAC
[0854] AATCAACATGCTACCCTCCGCGAGATCATCCGTGTTTCAAACCCGGCAGCTTAGT
[0855] TGCCGTTCTTCCGAATAGCATCGGTAACATGAGCAAAGTCTGCCGCCTTACAACG
[0856] GCTCTCCCGCTGACGCCGTCCCGGACTGATGGGCTGCCTGTATCGAGTGGTGATT
[0857] TTGTGCCGAGCTGCCGGTCGGGGAGCTGTTGGCTGGCTGGTGGCAGGATATATTG
[0858] TGGTGTAAACAAATTGACGCTTAGACAACTTAATAACACATTGCGGACGTTTTTA
[0859] ATGATCGAATACTAACGTCTCTACCACATT
[0860] 19. SEQ ID NO: 19 - HPV-16 LI - nucleic acid ATGTCTCTTTGGCTGCCTAGTGAGGCCACTGTCTACTTGCCTCCTGTCCCAGTATC
[0861] TAAGGTTGTAAGCACGGATGAATATGTTGCACGCACAAACATATATTATCATGCA
[0862] GGGACATCCAGACTACTTGCAGTTGGACATCCCTATTTTCCTATTAAAAAACCTA
[0863] ACAATAACAAAATATTAGTTCCTAAAGTATCAGGATTACAATACAGGGTATTTAG
[0864] AATACATTTACCTGACCCCAATAAGTTTGGTTTTCCTGACACCTCATTTTATAATC
[0865] CAGATACACAGCGGCTGGTTTGGGCCTGTGTAGGTGTTGAGGTAGGCCGTGGTCA
[0866] GCCATTAGGTGTGGGCATTAGTGGCCATCCTTTATTAAATAAATTGGATGACACA
[0867] GAAAATGCTAGTGCTTATGCAGCAAATGCAGGTGTGGATAATAGAGAATGTATA
[0868] TCTATGGATTACAAACAAACACAATTGTGTTTAATTGGTTGCAAACCACCTATAG
[0869] GGGAACACTGGGGCAAAGGATCCCCATGTACCAATGTTGCAGTAAATCCAGGTG
[0870] ATTGTCCACCATTAGAGTTAATAAACACAGTTATTCAGGATGGTGATATGGTTGA
[0871] TACTGGCTTTGGTGCTATGGACTTTACTACATTACAGGCTAACAAAAGTGAAGTT
[0872] CCACTGGATATTTGTACATCTATTTGCAAATATCCAGATTATATTAAAATGGTGTC
[0873] AGAACCATATGGCGACAGCTTATTTTTTTATTTACGGAGGGAACAAATGTTTGTT
[0874] AGACATTTATTTAATAGGGCTGGTGCTGTTGGTGAAAATGTACCAGACGATTTAT
[0875] ACATTAAAGGCTCTGGGTCTACTGCAAATTTAGCCAGTTCAAATTATTTTCCTAC
[0876] ACCTAGTGGTTCTATGGTTACCTCTGATGCCCAAATATTCAATAAACCTTATTGGT
[0877] TACAACGAGCACAGGGCCACAATAATGGCATTTGTTGGGGTAACCAACTATTTGT
[0878] TACTGTTGTTGATACTACACGCAGTACAAATATGTCATTATGTGCTGCCATATCTA
[0879] CTTCAGAAACTACATATAAAAATACTAACTTTAAGGAGTACCTACGACATGGGG
[0880] AGGAATATGATTTACAGTTTATTTTTCAACTGTGCAAAATAACCTTAACTGCAGA
[0881] CGTTATGACATACATACATTCTATGAATTCCACTATTTTGGAGGACTGGAATTTTG
[0882] GTCTACAACCTCCCCCAGGAGGCACACTAGAAGATACTTATAGGTTTGTAACATC
[0883] CCAGGCAATTGCTTGTCAAAAACATACACCTCCAGCACCTAAAGAAGATCCCCTT
[0884] AAAAAATACACTTTTTGGGAAGTAAATTTAAAGGAAAAGTTTTCTGCAGACCTAG
[0885] ATCAGTTTCCTTTAGGACGCAAATTTTTACTACAAGCAGGATTGAAGGCCAAACC
[0886] AAAATTTACATTAGGAAAACGAAAAGCTACACCCACCACCTCATCTACCTCTACA
[0887] ACTGCTAAACGCAAAAAACGTAAGCTGTAA
[0888] 20. SEQ ID NO : 20 - HPV- 16 L 1 - amino acid
[0889] MSLWLPSEATVYLPPVPVSKVVSTDEYVARTNIYYHAGTSRLLAVGHPYFPIKKPNN
[0890] NKILVPKVSGLQYRVFRIHLPDPNKFGFPDTSFYNPDTQRLVWACVGVEVGRGQPLG
[0891] VGISGHPLLNKLDDTENASAYAANAGVDNRECISMDYKQTQLCLIGCKPPIGEHWG KGSPCTNVAVNPGDCPPLELINTVIQDGDMVDTGFGAMDFTTLQANKSEVPLDICTSI
[0892] CKYPDYIKMVSEPYGDSLFFYLRREQMFVRHLFNRAGAVGENVPDDLYIKGSGSTA
[0893] NLASSNYFPTPSGSMVTSDAQIFNKPYWLQRAQGHNNGICWGNQLFVTVVDTTRST
[0894] NMSLCAAISTSETTYKNTNFKEYLRHGEEYDLQFIFQLCKITLTADVMTYIHSMNSTI
[0895] LEDWNFGLQPPPGGTLEDTYRFVTSQAIACQKHTPPAPKEDPLKKYTFWEVNLKEKF
[0896] SADLDQFPLGRKFLLQAGLKAKPKFTLGKRKATPTTSSTSTTAKRKKRKL*
[0897] 21. SEQ ID NO: 21 - 2C7 mimitope - amino acid
[0898] CGPIPVLDENGLFAPGPC
[0899] 22. SEQ ID NO: 22 - 2C7 mimitope - nucleic acid
[0900] TGCGGCCCTATCCCAGTGCTGGACGAGAACGGACTGTTTGCACCAGGACCTTGT
[0901] 23. SEQ ID NO: 23 - 2C7 mimitope (without flanking residues) - amino acid
[0902] IPVLDENGLFAP
[0903] 24. SEQ ID NO: 24 - 2C7 mimitope (without flanking residues) - nucleic acid
[0904] ATCCCAGTGCTGGACGAGAACGGACTGTTTGCACCA
[0905] 25. SEQ ID NO: 25 - pTRAkc-rbcsl-cTP with LI :2C7 DE_i Generation I
[0906] AATTCCGCCCCTAGAAATATTTGCGACTCTTCTGGCATGTAATATTTCGTTAAATA
[0907] TGAAGTGCTCCATTTTTATTAACTTTAAATAATTGGTTGTACGATCACTTTCTTAT
[0908] CAAGCGTTACTAAAATGCGTCAATCTCTTTGTTCTTCCATATTCATATGTCAAAAT
[0909] CTATCAAAATTCTTATATATCTTTTTCGAATTTGAAGTGAAATTTCGATAATTTAA
[0910] AATTAAATAGAACATATCATTATTTAGGTGTCATATTGATTTTTATACTTAATTAC
[0911] TAAATTTGGTTAACTTTGAAAGTGTACATCAACGAAAAATTAGTCAAACGACTAA
[0912] AATAAATAAATATCATGTGTTATTAAGAAAATTCTCCTATAAGAATATTTTAATA
[0913] GATCATATGTTTGTAAAAAAAATTAATTTTTACTAACACATATATTTACTTATCAA
[0914] AAATTTGACAAAGTAAGATTAAAATAATATTCATCTAACAAAAAAAAACCAGAA
[0915] AATGCTGAAAACCCGGCAAAACCGAACCAATCCAAACCGATATAGTTGGTTTGG
[0916] TTTGATTTTGATATAAACCGAACCAACTCGGTCCATTTGCACCCCTAATCATAAT
[0917] AGCTTTAATATTTCAAGATATTATTAAGTTAACGTTGTCAATATCCTGGAAATTTT
[0918] GCAAAATGAATCAAGCCTATATGGCTGTAATATGAATTTAAAAGCAGCTCGATGT GGTGGTAATATGTAATTTACTTGATTCTAAAAAAATATCCCAAGTATTAATAATT
[0919] TCTGCTAGGAAGAAGGTTAGCTACGATTTACAGCAAAGCCAGAATACAAAGAAC
[0920] CATAAAGTGATTGAAGCTCGAAATATACGAAGGAACAAATATTTTTAAAAAAAT
[0921] ACGCAATGACTTGGAACAAAAGAAAGTGATATATTTTTTGTTCTTAAACAAGCAT
[0922] CCCCTCTAAAGAATGGCAGTTTTCCTTTGCATGTAACTATTATGCTCCCTTCGTTA
[0923] CAAAAATTTTGGACTACTATTGGGCGCGGGGCGCGCCCGGTCCAAAGACCAGAG
[0924] GGCTATTGAGACTTTTCAACAAAGGGTAATATCGGGAAACCTCCTCGGATTCCAT
[0925] TGCCCAGCTATCTGTCACTTCATCGAAAGGACAGTAGAAAAGGAAGATGGCTTCT
[0926] ACAAATGCCATCATTGCGATAAAGGAAAGGCTATCGTTCAAGATGCCTCTACCG
[0927] ACAGTGGTCCCAAAGATGGACCCCCACCCACGAGGAACATCGTGGAAAAAGAAG
[0928] ACGTTCCAACCACGTCTTCAAAGCAAGTGGATTGATGTGATACATGGTGGAGCAC
[0929] GACACTCTCGTCTACTCCAAGAATATCAAAGATACAGTCTCAGAAGACCAGAGG
[0930] GCTATTGAGACTTTTCAACAAAGGGTAATATCGGGAAACCTCCTCGGATTCCATT
[0931] GCCCAGCTATCTGTCACTTCATCGAAAGGACAGTAGAAAAGGAAGATGGCTTCT
[0932] ACAAATGCCATCATTGCGATAAAGGAAAGGCTATCGTTCAAGATGCCTCTACCG
[0933] ACAGTGGTCCCAAAGATGGACCCCCACCCACGAGGAACATCGTGGAAAAAGAAG
[0934] ACGTTCCAACCACGTCTTCAAAGCAAGTGGATTGATGTGATATCTCCACTGACGT
[0935] AAGGGATGACGCACAATCCCACTATCCTTCGCAAGACCCTTCCTCTATATAAGGA
[0936] AGTTCATTTCATTTGGAGAGGACACGCTGAATTCACAACACAAATCAGATTTATA
[0937] GAGAGATTTATAAAAAAAAAAAAAACAATGGCTTCCTCTGTTATTTCCTCTGCAG
[0938] CTGTTGCTACACGCACCAATGTTACACAAGCTGGCAGCATGATTGCACCTTTCAC
[0939] TGGTCTCAAATCTGCTGCTACTTTCCCTGTTTCAAGGAAGCAAAACCTTGACATC
[0940] ACTTCCATTGCTAGCAATGGTGGACGCGTTAGGTTCATGAGTCTGTGGCTGCCAT
[0941] CTGAGGCAACCGTGTACCTGCCACCTGTGCCTGTGAGCAAGGTGGTGTCCACCGA
[0942] CGAGTATGTGGCCCGGACAAATATCTACTATCACGCAGGCACAAGCAGACTGCT
[0943] GGCAGTGGGCCACCCTTACTTCCCAATCAAGAAGCCTAACAATAACAAGATCCT
[0944] GGTGCCAAAGGTGAGCGGCCTGCAGTATAGGGTGTTCCGCATCCACCTGCCAGA
[0945] TCCCAATAAGTTCGGCTTTCCAGACACCTCCTTTTACAACCCCGATACACAGAGG
[0946] CTGGTGTGGGCATGCGTGGGAGTGGAAGTGGGAAGGGGCCAGCCACTGGGCGTG
[0947] GGCATCTCCGGCCACCCCCTGCTGAATAAGCTGGACGATACCGAGAACTGTGGC
[0948] CCTATCCCAGTGCTGGACGAGAACGGACTGTTTGCACCAGGACCTTGCGCATCCG
[0949] CCTACGCAGCAAATGCAGGAGTGGACAACAGGGAGTGTATCTCTATGGATTATA
[0950] AGCAGACCCAGCTGTGCCTGATCGGCTGTAAGCCACCAATCGGAGAGCACTGGG GCAAGGGATCTCCATGCACAAATGTGGCCGTGAACCCTGGCGACTGTCCTCCACT
[0951] GGAGCTGATCAATACCGTGATCCAGGACGGCGATATGGTGGACACAGGCTTCGG
[0952] CGCCATGGACTTCACCACCCTGCAGGCCAACAAGTCTGAGGTGCCTCTGGACATC
[0953] TGCACCAGCATCTGTAAGTACCCTGATTATATCAAGATGGTGAGCGAGCCATACG
[0954] GCGATTCCCTGTTCTTTTATCTGCGGAGAGAGCAGATGTTCGTGAGGCACCTGTT
[0955] TAATAGGGCAGGAGCAGTGGGAGAGAACGTGCCTGACGATCTGTACATCAAGGG
[0956] CTCCGGCTCTACCGCCAATCTGGCCAGCTCCAACTATTTCCCAACCCCCAGCGGC
[0957] TCCATGGTGACAAGCGACGCCCAGATCTTTAATAAGCCATACTGGCTGCAGAGG
[0958] GCCCAGGGCCACAATAACGGCATCTGCTGGGGCAATCAGCTGTTCGTGACCGTG
[0959] GTGGATACCACACGCTCTACAAACATGAGCCTGTGCGCCGCCATCTCTACCAGCG
[0960] AGACCACATACAAGAACACAAACTTTAAGGAGTACCTGCGGCACGGCGAGGAGT
[0961] ATGACCTGCAGTTCATCTTTCAGCTGTGCAAGATCACCCTGACAGCCGATGTGAT
[0962] GACCTACATCCACTCCATGAACAGCACAATCCTGGAGGACTGGAACTTCGGACT
[0963] GCAGCCACCTCCAGGAGGCACCCTGGAGGATACATATAGGTTTGTGACCTCTCAG
[0964] GCCATCGCCTGTCAGAAGCACACACCACCTGCACCAAAGGAGGACCCTCTGAAG
[0965] AAGTACACCTTCTGGGAGGTGAACCTGAAGGAGAAGTTTAGCGCCGACCTGGAT
[0966] CAGTTCCCACTGGGACGGAAGTTTCTGCTGCAGGCCGGCCTGAAGGCCAAGCCA
[0967] AAGTTCACCCTGGGCAAGAGAAAGGCCACCCCCACCACATCTAGCACATCCACC
[0968] ACAGCCAAGCGGAAGAAGAGAAAGCTGTAAGGATCCCTCGAGCTCGGATCCTCT
[0969] AGAGTCCGCAAAAATCACCAGTCTCTCTCTACAAATCTATCTCTCTCTATTTTTCT
[0970] CCAGAATAATGTGTGAGTAGTTCCCAGATAAGGGAATTAGGGTTCTTATAGGGTT
[0971] TCGCTCATGTGTTGAGCATATAAGAAACCCTTAGTATGTATTTGTATTTGTAAAAT
[0972] ACTTCTATCAATAAAATTTCTAATTCCTAAAACCAAAATCCAGTGACCGGGCGGC
[0973] CGGCCGCCCCTAGAAATATTTGCGACTCTTCTGGCATGTAATATTTCGTTAAATAT
[0974] GAAGTGCTCCATTTTTATTAACTTTAAATAATTGGTTGTACGATCACTTTCTTATC
[0975] AAGCGTTACTAAAATGCGTCAATCTCTTTGTTCTTCCATATTCATATGTCAAAATC
[0976] TATCAAAATTCTTATATATCTTTTTCGAATTTGAAGTGAAATTTCGATAATTTAAA
[0977] ATTAAATAGAACATATCATTATTTAGGTGTCATATTGATTTTTATACTTAATTACT
[0978] AAATTTGGTTAACTTTGAAAGTGTACATCAACGAAAAATTAGTCAAACGACTAA
[0979] AATAAATAAATATCATGTGTTATTAAGAAAATTCTCCTATAAGAATATTTTAATA
[0980] GATCATATGTTTGTAAAAAAAATTAATTTTTACTAACACATATATTTACTTATCAA
[0981] AAATTTGACAAAGTAAGATTAAAATAATATTCATCTAACAAAAAAAAACCAGAA
[0982] AATGCTGAAAACCCGGCAAAACCGAACCAATCCAAACCGATATAGTTGGTTTGG TTTGATTTTGATATAAACCGAACCAACTCGGTCCATTTGCACCCCTAATCATAAT
[0983] AGCTTTAATATTTCAAGATATTATTAAGTTAACGTTGTCAATATCCTGGAAATTTT
[0984] GCAAAATGAATCAAGCCTATATGGCTGTAATATGAATTTAAAAGCAGCTCGATGT
[0985] GGTGGTAATATGTAATTTACTTGATTCTAAAAAAATATCCCAAGTATTAATAATT
[0986] TCTGCTAGGAAGAAGGTTAGCTACGATTTACAGCAAAGCCAGAATACAAAGAAC
[0987] CATAAAGTGATTGAAGCTCGAAATATACGAAGGAACAAATATTTTTAAAAAAAT
[0988] ACGCAATGACTTGGAACAAAAGAAAGTGATATATTTTTTGTTCTTAAACAAGCAT
[0989] CCCCTCTAAAGAATGGCAGTTTTCCTTTGCATGTAACTATTATGCTCCCTTCGTTA
[0990] CAAAAATTTTGGACTACTATTGGGCGGGTGGAGGGGGATCAGATTGTCGTTTCCC
[0991] GCCTTCAGTTTAAACTATCAGTGTTTGACAGGATATATTGGCGGGTAAACCTAAG
[0992] AGAAAAGAGCGTTTATTAGAATAATCGGATATTTAAAAGGGCGTGAAAAGGTTT
[0993] ATCCGTTCGTCCATTTGTATGTGTACATCACCGACGAGCAAGGCAAGACCGAGCG
[0994] CCTTTCCGACGCTCACCGGGCTGGTTGCCCTCGCCGCTGGGCTGGCGGCCGTCTA
[0995] TGGCCCTGCAAACGCGCCAGAAACGCCGTCGAAGCCGTGTGCGAGACACCGGCC
[0996] GCCGGCGTTGTGGATACCTCGCGGAAAACTTGGCCCTCACTGACAGATGAGGGG
[0997] CGGACGTTGACACTTGAGGGGCCGACTCACCCGGCGCGGCGTTGACAGATGAGG
[0998] GGCAGGCTCGATTTCGGCCGGCGACGTGGAGCTGGCCAGCCTCGCAAATCGGCG
[0999] AAAACGCCTGATTTTACGCGAGTTTCCCACAGATGATGTGGACAAGCCTGGGGAT
[1000] AAGTGCCCTGCGGTATTGACACTTGAGGGGCGCGACTACTGACAGATGAGGGGC
[1001] GCGATCCTTGACACTTGAGGGGCAGAGTGCTGACAGATGAGGGGCGCACCTATT
[1002] GACATTTGAGGGGCTGTCCACAGGCAGAAAATCCAGCATTTGCAAGGGTTTCCG
[1003] CCCGTTTTTCGGCCACCGCTAACCTGTCTTTTAACCTGCTTTTAAACCAATATTTA
[1004] TAAACCTTGTTTTTAACCAGGGCTGCGCCCTGTGCGCGTGACCGCGCACGCCGAA
[1005] GGGGGGTGCCCCCCCTTCTCGAACCCTCCCGGCCCGCTAACGCGGGCCTCCCATC
[1006] CCCCCAGGGGCTGCGCCCCTCGGCCGCGAACGGCCTCACCCCAAAAATGGCAGC
[1007] GCTGGCAGTCCTTGCCATTGCCGGGATCGGGGCAGTAACGGGATGGGCGATCAG
[1008] CCCGACAAGCTACCCCTATTTGTTTATTTTTCTAAATACATTCAAATATGTATCCG
[1009] CTCATGAGACAATAACCCTGATAAATGCTTCAATAATATTGAAAAAGGAAGAGT
[1010] ATGAGTATTCAACATTTCCGTGTCGCCCTTATTCCCTTTTTTGCGGCATTTTGCCTT
[1011] CCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTAAAAGATGCTGAAGATCAGT
[1012] TGGGTGCACGAGTGGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTG
[1013] AGAGTTTTCGCCCCGAAGAACGTTTTCCAATGATGAGCACTTTTAAAGTTCTGCT
[1014] ATGTGGCGCGGTATTATCCCGTATTGACGCCGGGCAAGAGCAACTCGGTCGCCGC ATACACTATTCTCAGAATGACTTGGTTGAGTACTCACCAGTCACAGAAAAGCATC
[1015] TTACGGATGGCATGACAGTAAGAGAATTATGCAGTGCTGCCATAACCATGAGTG
[1016] ATAACACTGCGGCCAACTTACTTCTGACAACGATCGGAGGACCGAAGGAGCTAA
[1017] CCGCTTTTTTGCACAACATGGGGGATCATGTAACTCGCCTTGATCGTTGGGAACC
[1018] GGAGCTGAATGAAGCCATACCAAACGACGAGCGTGACACCACGATGCCTGTAGC
[1019] AATGGCAACAACGTTGCGCAAACTATTAACTGGCGAACTACTTACTCTAGCTTCC
[1020] CGGCAACAATTAATAGACTGGATGGAGGCGGATAAAGTTGCAGGACCACTTCTG
[1021] CGCTCGGCCCTTCCGGCTGGCTGGTTTATTGCTGATAAATCTGGAGCCGGTGAGC
[1022] GTGGGTCTCGCGGTATCATTGCAGCACTGGGGCCAGATGGTAAGCCCTCCCGTAT
[1023] CGTAGTTATCTACACGACGGGGAGTCAGGCAACTATGGATGAACGAAATAGACA
[1024] GATCGCTGAGATAGGTGCCTCACTGATTAAGCATTGGTAACTGTCAGACCAAGTT
[1025] TACTCATATATACTTTAGATTGATTTAAAACTTCATTTTTAATTTAAAAGGATCTA
[1026] GGTGAAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGT
[1027] TCCACTGAGCGTCAGACCCCGTAGAAAAGATCAAAGGATCTTCTTGAGATCCTTT
[1028] TTTTCTGCGCGTAATCTGCTGCTTGCAAACAAAAAAACCACCGCTACCAGCGGTG
[1029] GTTTGTTTGCCGGATCAAGAGCTACCAACTCTTTTTCCGAAGGTAACTGGCTTCA
[1030] GCAGAGCGCAGATACCAAATACTGTCCTTCTAGTGTAGCCGTAGTTAGGCCACCA
[1031] CTTCAAGAACTCTGTAGCACCGCCTACATACCTCGCTCTGCTAATCCTGTTACCA
[1032] GTGGCTGCTGCCAGTGGCGATAAGTCGTGTCTTACCGGGTTGGACTCAAGACGAT
[1033] AGTTACCGGATAAGGCGCAGCGGTCGGGCTGAACGGGGGGTTCGTGCACACAGC
[1034] CCAGCTTGGAGCGAACGACCTACACCGAACTGAGATACCTACAGCGTGAGCTAT
[1035] GAGAAAGCGCCACGCTTCCCGAAGGGAGAAAGGCGGACAGGTATCCGGTAAGC
[1036] GGCAGGGTCGGAACAGGAGAGCGCACGAGGGAGCTTCCAGGGGGAAACGCCTG
[1037] GTATCTTTATAGTCCTGTCGGGTTTCGCCACCTCTGACTTGAGCGTCGATTTTTGT
[1038] GATGCTCGTCAGGGGGGCGGAGCCTATGGAAAAACGCCAGCAACGCGGCCTTTT
[1039] TACGGTTCCTGGCCTTTTGCTGGCCTTTTGCTCACATGGACTCTAGCTAGAGGATC
[1040] ACAGGCAGCAACGCTCTGTCATCGTTACAATCAACATGCTACCCTCCGCGAGATC
[1041] ATCCGTGTTTCAAACCCGGCAGCTTAGTTGCCGTTCTTCCGAATAGCATCGGTAA
[1042] CATGAGCAAAGTCTGCCGCCTTACAACGGCTCTCCCGCTGACGCCGTCCCGGACT
[1043] GATGGGCTGCCTGTATCGAGTGGTGATTTTGTGCCGAGCTGCCGGTCGGGGAGCT
[1044] GTTGGCTGGCTGGTGGCAGGATATATTGTGGTGTAAACAAATTGACGCTTAGACA
[1045] ACTTAATAACACATTGCGGACGTTTTTAATGATCGAATACTAACGTCTCTACCAG
[1046] ATATCAGCTTGCATGCCGGTCGATCTAGTAACATAGATGACACCGCGCGCGATAA TTTATCCTAGTTTGCGCGCTATATTTTGTTTTCTATCGCGTATTAAATGTATAATTG
[1047] CGGGACTCTAATCATAAAAACCCATCTCATAAATAACGTCATGCATTACATGTTA
[1048] ATTATTACATGCTTAACGTAATTCAACAGAAATTATATGATAATCATCGCAAGAC
[1049] CGGCAACAGGATTCAATCTTAAGAAACTTTATTGCCAAATGTTTGAACGATCTGC
[1050] TTGACTCTAGCTAGAGTCCGAACCCCAGAGTCCCGCTCAGAAGAACTCGTCAAG
[1051] AAGGCGATAGAAGGCGATGCGCTGCGAATCGGGAGCGGCGATACCGTAAAGCA
[1052] CGAGGAAGCGGTCAGCCCATTCGCCGCCAAGCTCTTCAGCAATATCACGGGTAG
[1053] CCAACGCTATGTCCTGATAGCGGTCCGCCACACCCAGCCGGCCACAGTCGATGA
[1054] ATCCAGAAAAGCGGCCATTTTCCACCATGATATTCGGCAAGCAGGCATCGCCGTG
[1055] GGTCACGACGAGATCCTCGCCGTCGGGCATCCGCGCCTTGAGCCTGGCGAACAG
[1056] TTCGGCTGGCGCGAGCCCCTGATGCTCTTCGTCCAGATCATCCTGATCGACAAGA
[1057] CCGGCTTCCATCCGAGTACGTGCTCGCTCGATGCGATGTTTCGCTTGGTGGTCGA
[1058] ATGGGCAGGTAGCCGGATCAAGCGTATGCAGCCGCCGCATTGCATCAGCCATGA
[1059] TGGATACTTTCTCGGCAGGAGCAAGGTGAGATGACAGGAGATCCTGCCCCGGCA
[1060] CTTCGCCCAATAGCAGCCAGTTCCTTCCCGCTTCAGTGACAACGTCGAGCACAGC
[1061] TGCGCAAGGAACGCCCGTTGTGGCCAGCCACGATAGCCGCGCTGCCTCGTCTTGG
[1062] AGTTCATTCAGGGCACCGGACAGGTCGGTCTTGACAAAAAGAACCGGGCGCCCC
[1063] TGCGCTGACAGCCGGAACACGGCGGCATCAGAGCAGCCGATTGTTTGTTGTGCCC
[1064] AGTCATAGCCGAATAGCCTCTCCACCCAAGCGGCCGGAGAACCTGCGTGCAATC
[1065] CATCTTGTTCAATCATGCCTGCATCGAGTTGAGAGTGAATATGAGACTCTAATTG
[1066] GATACCGAGGGGAATTTATGGAACGTCAGTGGAGCATTTTTGACAAGAAATATTT
[1067] GCTAGCTGATAGTGACCTTAGGCGACTTTTGAACGCGCAATAATGGTTTCTGACG
[1068] TATGTGCTTAGCTCATTAAACTCCAGAAACCCGCGGCTCAGTGGCTCCTTCAACG
[1069] TTGCGGTTCTGTCAGTTCCAAACGTAAAACGGCTTGTCCCGCGTCATCGGCGGGG
[1070] GTCATAACGTGACTCCCTTAATTCTCCGCTCATGATCGATATCCATTGAAGAGCA AGCT
[1071] 26. SEQ ID NO: 26 - pTRAkc-rbcsl-cTP with L1:2C7 DE_s Generation I
[1072] AATTCCGCCCCTAGAAATATTTGCGACTCTTCTGGCATGTAATATTTCGTTAAATA
[1073] TGAAGTGCTCCATTTTTATTAACTTTAAATAATTGGTTGTACGATCACTTTCTTAT
[1074] CAAGCGTTACTAAAATGCGTCAATCTCTTTGTTCTTCCATATTCATATGTCAAAAT
[1075] CTATCAAAATTCTTATATATCTTTTTCGAATTTGAAGTGAAATTTCGATAATTTAA
[1076] AATTAAATAGAACATATCATTATTTAGGTGTCATATTGATTTTTATACTTAATTAC TAAATTTGGTTAACTTTGAAAGTGTACATCAACGAAAAATTAGTCAAACGACTAA
[1077] AATAAATAAATATCATGTGTTATTAAGAAAATTCTCCTATAAGAATATTTTAATA
[1078] GATCATATGTTTGTAAAAAAAATTAATTTTTACTAACACATATATTTACTTATCAA
[1079] AAATTTGACAAAGTAAGATTAAAATAATATTCATCTAACAAAAAAAAACCAGAA
[1080] AATGCTGAAAACCCGGCAAAACCGAACCAATCCAAACCGATATAGTTGGTTTGG
[1081] TTTGATTTTGATATAAACCGAACCAACTCGGTCCATTTGCACCCCTAATCATAAT
[1082] AGCTTTAATATTTCAAGATATTATTAAGTTAACGTTGTCAATATCCTGGAAATTTT
[1083] GCAAAATGAATCAAGCCTATATGGCTGTAATATGAATTTAAAAGCAGCTCGATGT
[1084] GGTGGTAATATGTAATTTACTTGATTCTAAAAAAATATCCCAAGTATTAATAATT
[1085] TCTGCTAGGAAGAAGGTTAGCTACGATTTACAGCAAAGCCAGAATACAAAGAAC
[1086] CATAAAGTGATTGAAGCTCGAAATATACGAAGGAACAAATATTTTTAAAAAAAT
[1087] ACGCAATGACTTGGAACAAAAGAAAGTGATATATTTTTTGTTCTTAAACAAGCAT
[1088] CCCCTCTAAAGAATGGCAGTTTTCCTTTGCATGTAACTATTATGCTCCCTTCGTTA
[1089] CAAAAATTTTGGACTACTATTGGGCGCGGGGCGCGCCCGGTCCAAAGACCAGAG
[1090] GGCTATTGAGACTTTTCAACAAAGGGTAATATCGGGAAACCTCCTCGGATTCCAT
[1091] TGCCCAGCTATCTGTCACTTCATCGAAAGGACAGTAGAAAAGGAAGATGGCTTCT
[1092] ACAAATGCCATCATTGCGATAAAGGAAAGGCTATCGTTCAAGATGCCTCTACCG
[1093] ACAGTGGTCCCAAAGATGGACCCCCACCCACGAGGAACATCGTGGAAAAAGAAG
[1094] ACGTTCCAACCACGTCTTCAAAGCAAGTGGATTGATGTGATACATGGTGGAGCAC
[1095] GACACTCTCGTCTACTCCAAGAATATCAAAGATACAGTCTCAGAAGACCAGAGG
[1096] GCTATTGAGACTTTTCAACAAAGGGTAATATCGGGAAACCTCCTCGGATTCCATT
[1097] GCCCAGCTATCTGTCACTTCATCGAAAGGACAGTAGAAAAGGAAGATGGCTTCT
[1098] ACAAATGCCATCATTGCGATAAAGGAAAGGCTATCGTTCAAGATGCCTCTACCG
[1099] ACAGTGGTCCCAAAGATGGACCCCCACCCACGAGGAACATCGTGGAAAAAGAAG
[1100] ACGTTCCAACCACGTCTTCAAAGCAAGTGGATTGATGTGATATCTCCACTGACGT
[1101] AAGGGATGACGCACAATCCCACTATCCTTCGCAAGACCCTTCCTCTATATAAGGA
[1102] AGTTCATTTCATTTGGAGAGGACACGCTGAATTCACAACACAAATCAGATTTATA
[1103] GAGAGATTTATAAAAAAAAAAAAAACAATGGCTTCCTCTGTTATTTCCTCTGCAG
[1104] CTGTTGCTACACGCACCAATGTTACACAAGCTGGCAGCATGATTGCACCTTTCAC
[1105] TGGTCTCAAATCTGCTGCTACTTTCCCTGTTTCAAGGAAGCAAAACCTTGACATC
[1106] ACTTCCATTGCTAGCAATGGTGGACGCGTTAGGTTCATGAGTCTGTGGCTGCCAT
[1107] CTGAGGCAACCGTGTACCTGCCACCTGTGCCTGTGAGCAAGGTGGTGTCCACCGA
[1108] CGAGTATGTGGCCCGGACAAACATCTACTATCACGCAGGCACAAGCAGACTGCT GGCAGTGGGCCACCCTTACTTCCCAATCAAGAAGCCTAACAATAACAAGATCCT
[1109] GGTGCCAAAGGTGTCCGGCCTGCAGTATAGGGTGTTCCGCATCCACCTGCCAGAT
[1110] CCCAATAAGTTCGGCTTTCCAGACACCTCTTTTTACAACCCCGATACACAGAGGC
[1111] TGGTGTGGGCATGCGTGGGAGTGGAAGTGGGAAGGGGCCAGCCACTGGGAGTGG
[1112] GAATCTCTGGACACCCACTGCTGAATAAGCTGGACGATACCGAGTGCGGCCCTAT
[1113] CCCAGTGCTGGACGAGAACGGACTGTTTGCACCAGGACCTTGTATGGATTATAAG
[1114] CAGACCCAGCTGTGCCTGATCGGCTGTAAGCCACCAATCGGAGAGCACTGGGGC
[1115] AAGGGATCCCCATGCACAAATGTGGCCGTGAACCCTGGCGACTGTCCTCCACTGG
[1116] AGCTGATCAATACCGTGATCCAGGACGGCGATATGGTGGACACAGGCTTCGGCG
[1117] CCATGGACTTCACCACCCTGCAGGCCAACAAGTCTGAGGTGCCTCTGGACATCTG
[1118] CACCAGCATCTGTAAGTACCCTGATTATATCAAGATGGTGAGCGAGCCATACGGC
[1119] GATTCCCTGTTCTTTTATCTGCGGAGAGAGCAGATGTTCGTGAGGCACCTGTTTA
[1120] ATAGGGCAGGAGCAGTGGGAGAGAACGTGCCTGACGATCTGTACATCAAGGGCT
[1121] CCGGCTCTACCGCCAATCTGGCCAGCTCCAACTATTTCCCAACCCCCAGCGGCTC
[1122] CATGGTGACAAGCGACGCCCAGATCTTTAATAAGCCATACTGGCTGCAGAGGGC
[1123] CCAGGGCCACAATAACGGCATCTGCTGGGGCAATCAGCTGTTCGTGACCGTGGT
[1124] GGATACCACACGCTCTACAAACATGAGCCTGTGCGCCGCCATCTCTACCAGCGAG
[1125] ACCACATACAAGAACACAAACTTTAAGGAGTACCTGCGGCACGGCGAGGAGTAT
[1126] GACCTGCAGTTCATCTTTCAGCTGTGCAAGATCACCCTGACAGCCGATGTGATGA
[1127] CCTACATCCACTCCATGAACAGCACAATCCTGGAGGACTGGAACTTCGGACTGCA
[1128] GCCACCTCCAGGAGGCACCCTGGAGGATACATATAGGTTTGTGACCAGCCAGGC
[1129] CATCGCCTGTCAGAAGCACACACCACCTGCACCAAAGGAGGACCCTCTGAAGAA
[1130] GTACACCTTCTGGGAGGTGAACCTGAAGGAGAAGTTTTCCGCCGACCTGGATCA
[1131] GTTCCCACTGGGACGGAAGTTTCTGCTGCAGGCCGGCCTGAAGGCCAAGCCAAA
[1132] GTTCACCCTGGGCAAGAGAAAGGCCACCCCCACCACATCTAGCACATCCACCAC
[1133] AGCCAAGCGGAAGAAGAGAAAGCTGTAAGGATCCCTCGAGCTCGGATCCTCTAG
[1134] AGTCCGCAAAAATCACCAGTCTCTCTCTACAAATCTATCTCTCTCTATTTTTCTCC
[1135] AGAATAATGTGTGAGTAGTTCCCAGATAAGGGAATTAGGGTTCTTATAGGGTTTC
[1136] GCTCATGTGTTGAGCATATAAGAAACCCTTAGTATGTATTTGTATTTGTAAAATA
[1137] CTTCTATCAATAAAATTTCTAATTCCTAAAACCAAAATCCAGTGACCGGGCGGCC
[1138] GGCCGCCCCTAGAAATATTTGCGACTCTTCTGGCATGTAATATTTCGTTAAATAT
[1139] GAAGTGCTCCATTTTTATTAACTTTAAATAATTGGTTGTACGATCACTTTCTTATC
[1140] AAGCGTTACTAAAATGCGTCAATCTCTTTGTTCTTCCATATTCATATGTCAAAATC TATCAAAATTCTTATATATCTTTTTCGAATTTGAAGTGAAATTTCGATAATTTAAA
[1141] ATTAAATAGAACATATCATTATTTAGGTGTCATATTGATTTTTATACTTAATTACT
[1142] AAATTTGGTTAACTTTGAAAGTGTACATCAACGAAAAATTAGTCAAACGACTAA
[1143] AATAAATAAATATCATGTGTTATTAAGAAAATTCTCCTATAAGAATATTTTAATA
[1144] GATCATATGTTTGTAAAAAAAATTAATTTTTACTAACACATATATTTACTTATCAA
[1145] AAATTTGACAAAGTAAGATTAAAATAATATTCATCTAACAAAAAAAAACCAGAA
[1146] AATGCTGAAAACCCGGCAAAACCGAACCAATCCAAACCGATATAGTTGGTTTGG
[1147] TTTGATTTTGATATAAACCGAACCAACTCGGTCCATTTGCACCCCTAATCATAAT
[1148] AGCTTTAATATTTCAAGATATTATTAAGTTAACGTTGTCAATATCCTGGAAATTTT
[1149] GCAAAATGAATCAAGCCTATATGGCTGTAATATGAATTTAAAAGCAGCTCGATGT
[1150] GGTGGTAATATGTAATTTACTTGATTCTAAAAAAATATCCCAAGTATTAATAATT
[1151] TCTGCTAGGAAGAAGGTTAGCTACGATTTACAGCAAAGCCAGAATACAAAGAAC
[1152] CATAAAGTGATTGAAGCTCGAAATATACGAAGGAACAAATATTTTTAAAAAAAT
[1153] ACGCAATGACTTGGAACAAAAGAAAGTGATATATTTTTTGTTCTTAAACAAGCAT
[1154] CCCCTCTAAAGAATGGCAGTTTTCCTTTGCATGTAACTATTATGCTCCCTTCGTTA
[1155] CAAAAATTTTGGACTACTATTGGGCGGGTGGAGGGGGATCAGATTGTCGTTTCCC
[1156] GCCTTCAGTTTAAACTATCAGTGTTTGACAGGATATATTGGCGGGTAAACCTAAG
[1157] AGAAAAGAGCGTTTATTAGAATAATCGGATATTTAAAAGGGCGTGAAAAGGTTT
[1158] ATCCGTTCGTCCATTTGTATGTGTACATCACCGACGAGCAAGGCAAGACCGAGCG
[1159] CCTTTCCGACGCTCACCGGGCTGGTTGCCCTCGCCGCTGGGCTGGCGGCCGTCTA
[1160] TGGCCCTGCAAACGCGCCAGAAACGCCGTCGAAGCCGTGTGCGAGACACCGGCC
[1161] GCCGGCGTTGTGGATACCTCGCGGAAAACTTGGCCCTCACTGACAGATGAGGGG
[1162] CGGACGTTGACACTTGAGGGGCCGACTCACCCGGCGCGGCGTTGACAGATGAGG
[1163] GGCAGGCTCGATTTCGGCCGGCGACGTGGAGCTGGCCAGCCTCGCAAATCGGCG
[1164] AAAACGCCTGATTTTACGCGAGTTTCCCACAGATGATGTGGACAAGCCTGGGGAT
[1165] AAGTGCCCTGCGGTATTGACACTTGAGGGGCGCGACTACTGACAGATGAGGGGC
[1166] GCGATCCTTGACACTTGAGGGGCAGAGTGCTGACAGATGAGGGGCGCACCTATT
[1167] GACATTTGAGGGGCTGTCCACAGGCAGAAAATCCAGCATTTGCAAGGGTTTCCG
[1168] CCCGTTTTTCGGCCACCGCTAACCTGTCTTTTAACCTGCTTTTAAACCAATATTTA
[1169] TAAACCTTGTTTTTAACCAGGGCTGCGCCCTGTGCGCGTGACCGCGCACGCCGAA
[1170] GGGGGGTGCCCCCCCTTCTCGAACCCTCCCGGCCCGCTAACGCGGGCCTCCCATC
[1171] CCCCCAGGGGCTGCGCCCCTCGGCCGCGAACGGCCTCACCCCAAAAATGGCAGC
[1172] GCTGGCAGTCCTTGCCATTGCCGGGATCGGGGCAGTAACGGGATGGGCGATCAG CCCGACAAGCTACCCCTATTTGTTTATTTTTCTAAATACATTCAAATATGTATCCG
[1173] CTCATGAGACAATAACCCTGATAAATGCTTCAATAATATTGAAAAAGGAAGAGT
[1174] ATGAGTATTCAACATTTCCGTGTCGCCCTTATTCCCTTTTTTGCGGCATTTTGCCTT
[1175] CCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTAAAAGATGCTGAAGATCAGT
[1176] TGGGTGCACGAGTGGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTG
[1177] AGAGTTTTCGCCCCGAAGAACGTTTTCCAATGATGAGCACTTTTAAAGTTCTGCT
[1178] ATGTGGCGCGGTATTATCCCGTATTGACGCCGGGCAAGAGCAACTCGGTCGCCGC
[1179] ATACACTATTCTCAGAATGACTTGGTTGAGTACTCACCAGTCACAGAAAAGCATC
[1180] TTACGGATGGCATGACAGTAAGAGAATTATGCAGTGCTGCCATAACCATGAGTG
[1181] ATAACACTGCGGCCAACTTACTTCTGACAACGATCGGAGGACCGAAGGAGCTAA
[1182] CCGCTTTTTTGCACAACATGGGGGATCATGTAACTCGCCTTGATCGTTGGGAACC
[1183] GGAGCTGAATGAAGCCATACCAAACGACGAGCGTGACACCACGATGCCTGTAGC
[1184] AATGGCAACAACGTTGCGCAAACTATTAACTGGCGAACTACTTACTCTAGCTTCC
[1185] CGGCAACAATTAATAGACTGGATGGAGGCGGATAAAGTTGCAGGACCACTTCTG
[1186] CGCTCGGCCCTTCCGGCTGGCTGGTTTATTGCTGATAAATCTGGAGCCGGTGAGC
[1187] GTGGGTCTCGCGGTATCATTGCAGCACTGGGGCCAGATGGTAAGCCCTCCCGTAT
[1188] CGTAGTTATCTACACGACGGGGAGTCAGGCAACTATGGATGAACGAAATAGACA
[1189] GATCGCTGAGATAGGTGCCTCACTGATTAAGCATTGGTAACTGTCAGACCAAGTT
[1190] TACTCATATATACTTTAGATTGATTTAAAACTTCATTTTTAATTTAAAAGGATCTA
[1191] GGTGAAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGT
[1192] TCCACTGAGCGTCAGACCCCGTAGAAAAGATCAAAGGATCTTCTTGAGATCCTTT
[1193] TTTTCTGCGCGTAATCTGCTGCTTGCAAACAAAAAAACCACCGCTACCAGCGGTG
[1194] GTTTGTTTGCCGGATCAAGAGCTACCAACTCTTTTTCCGAAGGTAACTGGCTTCA
[1195] GCAGAGCGCAGATACCAAATACTGTCCTTCTAGTGTAGCCGTAGTTAGGCCACCA
[1196] CTTCAAGAACTCTGTAGCACCGCCTACATACCTCGCTCTGCTAATCCTGTTACCA
[1197] GTGGCTGCTGCCAGTGGCGATAAGTCGTGTCTTACCGGGTTGGACTCAAGACGAT
[1198] AGTTACCGGATAAGGCGCAGCGGTCGGGCTGAACGGGGGGTTCGTGCACACAGC
[1199] CCAGCTTGGAGCGAACGACCTACACCGAACTGAGATACCTACAGCGTGAGCTAT
[1200] GAGAAAGCGCCACGCTTCCCGAAGGGAGAAAGGCGGACAGGTATCCGGTAAGC
[1201] GGCAGGGTCGGAACAGGAGAGCGCACGAGGGAGCTTCCAGGGGGAAACGCCTG
[1202] GTATCTTTATAGTCCTGTCGGGTTTCGCCACCTCTGACTTGAGCGTCGATTTTTGT
[1203] GATGCTCGTCAGGGGGGCGGAGCCTATGGAAAAACGCCAGCAACGCGGCCTTTT
[1204] TACGGTTCCTGGCCTTTTGCTGGCCTTTTGCTCACATGGACTCTAGCTAGAGGATC ACAGGCAGCAACGCTCTGTCATCGTTACAATCAACATGCTACCCTCCGCGAGATC
[1205] ATCCGTGTTTCAAACCCGGCAGCTTAGTTGCCGTTCTTCCGAATAGCATCGGTAA
[1206] CATGAGCAAAGTCTGCCGCCTTACAACGGCTCTCCCGCTGACGCCGTCCCGGACT
[1207] GATGGGCTGCCTGTATCGAGTGGTGATTTTGTGCCGAGCTGCCGGTCGGGGAGCT
[1208] GTTGGCTGGCTGGTGGCAGGATATATTGTGGTGTAAACAAATTGACGCTTAGACA
[1209] ACTTAATAACACATTGCGGACGTTTTTAATGATCGAATACTAACGTCTCTACCAG
[1210] ATATCAGCTTGCATGCCGGTCGATCTAGTAACATAGATGACACCGCGCGCGATAA
[1211] TTTATCCTAGTTTGCGCGCTATATTTTGTTTTCTATCGCGTATTAAATGTATAATTG
[1212] CGGGACTCTAATCATAAAAACCCATCTCATAAATAACGTCATGCATTACATGTTA
[1213] ATTATTACATGCTTAACGTAATTCAACAGAAATTATATGATAATCATCGCAAGAC
[1214] CGGCAACAGGATTCAATCTTAAGAAACTTTATTGCCAAATGTTTGAACGATCTGC
[1215] TTGACTCTAGCTAGAGTCCGAACCCCAGAGTCCCGCTCAGAAGAACTCGTCAAG
[1216] AAGGCGATAGAAGGCGATGCGCTGCGAATCGGGAGCGGCGATACCGTAAAGCA
[1217] CGAGGAAGCGGTCAGCCCATTCGCCGCCAAGCTCTTCAGCAATATCACGGGTAG
[1218] CCAACGCTATGTCCTGATAGCGGTCCGCCACACCCAGCCGGCCACAGTCGATGA
[1219] ATCCAGAAAAGCGGCCATTTTCCACCATGATATTCGGCAAGCAGGCATCGCCGTG
[1220] GGTCACGACGAGATCCTCGCCGTCGGGCATCCGCGCCTTGAGCCTGGCGAACAG
[1221] TTCGGCTGGCGCGAGCCCCTGATGCTCTTCGTCCAGATCATCCTGATCGACAAGA
[1222] CCGGCTTCCATCCGAGTACGTGCTCGCTCGATGCGATGTTTCGCTTGGTGGTCGA
[1223] ATGGGCAGGTAGCCGGATCAAGCGTATGCAGCCGCCGCATTGCATCAGCCATGA
[1224] TGGATACTTTCTCGGCAGGAGCAAGGTGAGATGACAGGAGATCCTGCCCCGGCA
[1225] CTTCGCCCAATAGCAGCCAGTTCCTTCCCGCTTCAGTGACAACGTCGAGCACAGC
[1226] TGCGCAAGGAACGCCCGTTGTGGCCAGCCACGATAGCCGCGCTGCCTCGTCTTGG
[1227] AGTTCATTCAGGGCACCGGACAGGTCGGTCTTGACAAAAAGAACCGGGCGCCCC
[1228] TGCGCTGACAGCCGGAACACGGCGGCATCAGAGCAGCCGATTGTTTGTTGTGCCC
[1229] AGTCATAGCCGAATAGCCTCTCCACCCAAGCGGCCGGAGAACCTGCGTGCAATC
[1230] CATCTTGTTCAATCATGCCTGCATCGAGTTGAGAGTGAATATGAGACTCTAATTG
[1231] GATACCGAGGGGAATTTATGGAACGTCAGTGGAGCATTTTTGACAAGAAATATTT
[1232] GCTAGCTGATAGTGACCTTAGGCGACTTTTGAACGCGCAATAATGGTTTCTGACG
[1233] TATGTGCTTAGCTCATTAAACTCCAGAAACCCGCGGCTCAGTGGCTCCTTCAACG
[1234] TTGCGGTTCTGTCAGTTCCAAACGTAAAACGGCTTGTCCCGCGTCATCGGCGGGG
[1235] GTCATAACGTGACTCCCTTAATTCTCCGCTCATGATCGATATCCATTGAAGAGCA
[1236] AGCT 27. SEQ ID NO: 27 - pTRAkc-rbcsl-cTP L1:2C7 h4J (Generation I)
[1237] AATTCCGCCCCTAGAAATATTTGCGACTCTTCTGGCATGTAATATTTCGTTAAATA
[1238] TGAAGTGCTCCATTTTTATTAACTTTAAATAATTGGTTGTACGATCACTTTCTTAT
[1239] CAAGCGTTACTAAAATGCGTCAATCTCTTTGTTCTTCCATATTCATATGTCAAAAT
[1240] CTATCAAAATTCTTATATATCTTTTTCGAATTTGAAGTGAAATTTCGATAATTTAA
[1241] AATTAAATAGAACATATCATTATTTAGGTGTCATATTGATTTTTATACTTAATTAC
[1242] TAAATTTGGTTAACTTTGAAAGTGTACATCAACGAAAAATTAGTCAAACGACTAA
[1243] AATAAATAAATATCATGTGTTATTAAGAAAATTCTCCTATAAGAATATTTTAATA
[1244] GATCATATGTTTGTAAAAAAAATTAATTTTTACTAACACATATATTTACTTATCAA
[1245] AAATTTGACAAAGTAAGATTAAAATAATATTCATCTAACAAAAAAAAACCAGAA
[1246] AATGCTGAAAACCCGGCAAAACCGAACCAATCCAAACCGATATAGTTGGTTTGG
[1247] TTTGATTTTGATATAAACCGAACCAACTCGGTCCATTTGCACCCCTAATCATAAT
[1248] AGCTTTAATATTTCAAGATATTATTAAGTTAACGTTGTCAATATCCTGGAAATTTT
[1249] GCAAAATGAATCAAGCCTATATGGCTGTAATATGAATTTAAAAGCAGCTCGATGT
[1250] GGTGGTAATATGTAATTTACTTGATTCTAAAAAAATATCCCAAGTATTAATAATT
[1251] TCTGCTAGGAAGAAGGTTAGCTACGATTTACAGCAAAGCCAGAATACAAAGAAC
[1252] CATAAAGTGATTGAAGCTCGAAATATACGAAGGAACAAATATTTTTAAAAAAAT
[1253] ACGCAATGACTTGGAACAAAAGAAAGTGATATATTTTTTGTTCTTAAACAAGCAT
[1254] CCCCTCTAAAGAATGGCAGTTTTCCTTTGCATGTAACTATTATGCTCCCTTCGTTA
[1255] CAAAAATTTTGGACTACTATTGGGCGCGGGGCGCGCCCGGTCCAAAGACCAGAG
[1256] GGCTATTGAGACTTTTCAACAAAGGGTAATATCGGGAAACCTCCTCGGATTCCAT
[1257] TGCCCAGCTATCTGTCACTTCATCGAAAGGACAGTAGAAAAGGAAGATGGCTTCT
[1258] ACAAATGCCATCATTGCGATAAAGGAAAGGCTATCGTTCAAGATGCCTCTACCG
[1259] ACAGTGGTCCCAAAGATGGACCCCCACCCACGAGGAACATCGTGGAAAAAGAAG
[1260] ACGTTCCAACCACGTCTTCAAAGCAAGTGGATTGATGTGATACATGGTGGAGCAC
[1261] GACACTCTCGTCTACTCCAAGAATATCAAAGATACAGTCTCAGAAGACCAGAGG
[1262] GCTATTGAGACTTTTCAACAAAGGGTAATATCGGGAAACCTCCTCGGATTCCATT
[1263] GCCCAGCTATCTGTCACTTCATCGAAAGGACAGTAGAAAAGGAAGATGGCTTCT
[1264] ACAAATGCCATCATTGCGATAAAGGAAAGGCTATCGTTCAAGATGCCTCTACCG
[1265] ACAGTGGTCCCAAAGATGGACCCCCACCCACGAGGAACATCGTGGAAAAAGAAG
[1266] ACGTTCCAACCACGTCTTCAAAGCAAGTGGATTGATGTGATATCTCCACTGACGT
[1267] AAGGGATGACGCACAATCCCACTATCCTTCGCAAGACCCTTCCTCTATATAAGGA AGTTCATTTCATTTGGAGAGGACACGCTGAATTCACAACACAAATCAGATTTATA
[1268] GAGAGATTTATAAAAAAAAAAAAAACAATGGCTTCCTCTGTTATTTCCTCTGCAG
[1269] CTGTTGCTACACGCACCAATGTTACACAAGCTGGCAGCATGATTGCACCTTTCAC
[1270] TGGTCTCAAATCTGCTGCTACTTTCCCTGTTTCAAGGAAGCAAAACCTTGACATC
[1271] ACTTCCATTGCTAGCAATGGTGGACGCGTTAGGTTCATGAGTCTGTGGCTGCCAT
[1272] CTGAGGCAACCGTGTACCTGCCACCTGTGCCTGTGAGCAAGGTGGTGTCCACCGA
[1273] TGAGTATGTGGCCCGGACAAATATCTACTATCACGCAGGCACATCCAGACTGCTG
[1274] GCAGTGGGCCACCCTTACTTCCCAATCAAGAAGCCTAACAATAACAAGATCCTG
[1275] GTGCCAAAGGTGTCCGGCCTGCAGTATAGGGTGTTCCGCATCCACCTGCCAGACC
[1276] CCAATAAGTTCGGCTTTCCAGACACCTCTTTTTACAACCCCGATACACAGAGGCT
[1277] GGTGTGGGCATGCGTGGGAGTGGAAGTGGGAAGGGGCCAGCCACTGGGCGTGG
[1278] GCATCTCCGGCCACCCCCTGCTGAATAAGCTGGACGATACCGAGAACGCCTCTGC
[1279] CTACGCAGCAAATGCAGGAGTGGACAACAGGGAGTGTATCAGCATGGATTATAA
[1280] GCAGACCCAGCTGTGCCTGATCGGCTGTAAGCCACCAATCGGAGAGCACTGGGG
[1281] CAAGGGATCTCCATGCACAAATGTGGCCGTGAACCCTGGCGATTGTCCTCCACTG
[1282] GAGCTGATCAATACCGTGATCCAGGACGGCGATATGGTGGACACAGGCTTCGGC
[1283] GCCATGGACTTCACCACCCTGCAGGCCAACAAGTCTGAGGTGCCTCTGGACATCT
[1284] GCACCAGCATCTGTAAGTACCCTGATTATATCAAGATGGTGAGCGAGCCATACG
[1285] GCGACTCCCTGTTCTTTTATCTGCGGAGAGAGCAGATGTTCGTGAGGCACCTGTT
[1286] TAATAGGGCAGGAGCAGTGGGAGAGAACGTGCCTGACGATCTGTACATCAAGGG
[1287] CTCCGGCTCTACCGCCAATCTGGCCAGCTCCAACTATTTCCCTACCCCAAGCGGC
[1288] TCCATGGTGACAAGCGATGCCCAGATCTTTAACAAGCCATACTGGCTGCAGAGG
[1289] GCCCAGGGCCACAATAACGGCATCTGCTGGGGCAATCAGCTGTTCGTGACCGTG
[1290] GTGGACACCACACGCTCTACAAACATGAGCCTGTGCGCCGCCATCTCTACCAGCG
[1291] AGACCACATACAAGAACACAAACTTTAAGGAGTACCTGCGGCACGGCGAGGAGT
[1292] ATGACCTGCAGTTCATCTTTCAGCTGTGCAAGATCACCCTGACAGCCGATGTGAT
[1293] GACCTACATCCACTCCATGAACAGCACAATCCTGGAGGACTGGAACTTCGGCCTG
[1294] CAGCCACCTCCAGGAGGCACCCTGTGCGGACCAATCCCTGTGCTGGACGAGAAT
[1295] GGACTGTTCGCACCAGGACCATGCGAGGATACCTATAGGTTTGTGACAAGCCAG
[1296] GCCATCGCATGTCAGAAGCACACCCCACCTGCACCAAAGGAGGACCCTCTGAAG
[1297] AAGTACACATTCTGGGAGGTGAACCTGAAGGAGAAGTTTTCCGCCGACCTGGAT
[1298] CAGTTCCCACTGGGACGGAAGTTTCTGCTGCAGGCCGGCCTGAAGGCCAAGCCA
[1299] AAGTTTACCCTGGGCAAGAGAAAGGCCACCCCCACCACATCTAGCACAAGCACC ACAGCCAAGCGGAAGAAGAGAAAGCTGTAAGGATCCCTCGAGCTCGGATCCTCT
[1300] AGAGTCCGCAAAAATCACCAGTCTCTCTCTACAAATCTATCTCTCTCTATTTTTCT
[1301] CCAGAATAATGTGTGAGTAGTTCCCAGATAAGGGAATTAGGGTTCTTATAGGGTT
[1302] TCGCTCATGTGTTGAGCATATAAGAAACCCTTAGTATGTATTTGTATTTGTAAAAT
[1303] ACTTCTATCAATAAAATTTCTAATTCCTAAAACCAAAATCCAGTGACCGGGCGGC
[1304] CGGCCGCCCCTAGAAATATTTGCGACTCTTCTGGCATGTAATATTTCGTTAAATAT
[1305] GAAGTGCTCCATTTTTATTAACTTTAAATAATTGGTTGTACGATCACTTTCTTATC
[1306] AAGCGTTACTAAAATGCGTCAATCTCTTTGTTCTTCCATATTCATATGTCAAAATC
[1307] TATCAAAATTCTTATATATCTTTTTCGAATTTGAAGTGAAATTTCGATAATTTAAA
[1308] ATTAAATAGAACATATCATTATTTAGGTGTCATATTGATTTTTATACTTAATTACT
[1309] AAATTTGGTTAACTTTGAAAGTGTACATCAACGAAAAATTAGTCAAACGACTAA
[1310] AATAAATAAATATCATGTGTTATTAAGAAAATTCTCCTATAAGAATATTTTAATA
[1311] GATCATATGTTTGTAAAAAAAATTAATTTTTACTAACACATATATTTACTTATCAA
[1312] AAATTTGACAAAGTAAGATTAAAATAATATTCATCTAACAAAAAAAAACCAGAA
[1313] AATGCTGAAAACCCGGCAAAACCGAACCAATCCAAACCGATATAGTTGGTTTGG
[1314] TTTGATTTTGATATAAACCGAACCAACTCGGTCCATTTGCACCCCTAATCATAAT
[1315] AGCTTTAATATTTCAAGATATTATTAAGTTAACGTTGTCAATATCCTGGAAATTTT
[1316] GCAAAATGAATCAAGCCTATATGGCTGTAATATGAATTTAAAAGCAGCTCGATGT
[1317] GGTGGTAATATGTAATTTACTTGATTCTAAAAAAATATCCCAAGTATTAATAATT
[1318] TCTGCTAGGAAGAAGGTTAGCTACGATTTACAGCAAAGCCAGAATACAAAGAAC
[1319] CATAAAGTGATTGAAGCTCGAAATATACGAAGGAACAAATATTTTTAAAAAAAT
[1320] ACGCAATGACTTGGAACAAAAGAAAGTGATATATTTTTTGTTCTTAAACAAGCAT
[1321] CCCCTCTAAAGAATGGCAGTTTTCCTTTGCATGTAACTATTATGCTCCCTTCGTTA
[1322] CAAAAATTTTGGACTACTATTGGGCGGGTGGAGGGGGATCAGATTGTCGTTTCCC
[1323] GCCTTCAGTTTAAACTATCAGTGTTTGACAGGATATATTGGCGGGTAAACCTAAG
[1324] AGAAAAGAGCGTTTATTAGAATAATCGGATATTTAAAAGGGCGTGAAAAGGTTT
[1325] ATCCGTTCGTCCATTTGTATGTGTACATCACCGACGAGCAAGGCAAGACCGAGCG
[1326] CCTTTCCGACGCTCACCGGGCTGGTTGCCCTCGCCGCTGGGCTGGCGGCCGTCTA
[1327] TGGCCCTGCAAACGCGCCAGAAACGCCGTCGAAGCCGTGTGCGAGACACCGGCC
[1328] GCCGGCGTTGTGGATACCTCGCGGAAAACTTGGCCCTCACTGACAGATGAGGGG
[1329] CGGACGTTGACACTTGAGGGGCCGACTCACCCGGCGCGGCGTTGACAGATGAGG
[1330] GGCAGGCTCGATTTCGGCCGGCGACGTGGAGCTGGCCAGCCTCGCAAATCGGCG
[1331] AAAACGCCTGATTTTACGCGAGTTTCCCACAGATGATGTGGACAAGCCTGGGGAT AAGTGCCCTGCGGTATTGACACTTGAGGGGCGCGACTACTGACAGATGAGGGGC
[1332] GCGATCCTTGACACTTGAGGGGCAGAGTGCTGACAGATGAGGGGCGCACCTATT
[1333] GACATTTGAGGGGCTGTCCACAGGCAGAAAATCCAGCATTTGCAAGGGTTTCCG
[1334] CCCGTTTTTCGGCCACCGCTAACCTGTCTTTTAACCTGCTTTTAAACCAATATTTA
[1335] TAAACCTTGTTTTTAACCAGGGCTGCGCCCTGTGCGCGTGACCGCGCACGCCGAA
[1336] GGGGGGTGCCCCCCCTTCTCGAACCCTCCCGGCCCGCTAACGCGGGCCTCCCATC
[1337] CCCCCAGGGGCTGCGCCCCTCGGCCGCGAACGGCCTCACCCCAAAAATGGCAGC
[1338] GCTGGCAGTCCTTGCCATTGCCGGGATCGGGGCAGTAACGGGATGGGCGATCAG
[1339] CCCGACAAGCTACCCCTATTTGTTTATTTTTCTAAATACATTCAAATATGTATCCG
[1340] CTCATGAGACAATAACCCTGATAAATGCTTCAATAATATTGAAAAAGGAAGAGT
[1341] ATGAGTATTCAACATTTCCGTGTCGCCCTTATTCCCTTTTTTGCGGCATTTTGCCTT
[1342] CCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTAAAAGATGCTGAAGATCAGT
[1343] TGGGTGCACGAGTGGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTG
[1344] AGAGTTTTCGCCCCGAAGAACGTTTTCCAATGATGAGCACTTTTAAAGTTCTGCT
[1345] ATGTGGCGCGGTATTATCCCGTATTGACGCCGGGCAAGAGCAACTCGGTCGCCGC
[1346] ATACACTATTCTCAGAATGACTTGGTTGAGTACTCACCAGTCACAGAAAAGCATC
[1347] TTACGGATGGCATGACAGTAAGAGAATTATGCAGTGCTGCCATAACCATGAGTG
[1348] ATAACACTGCGGCCAACTTACTTCTGACAACGATCGGAGGACCGAAGGAGCTAA
[1349] CCGCTTTTTTGCACAACATGGGGGATCATGTAACTCGCCTTGATCGTTGGGAACC
[1350] GGAGCTGAATGAAGCCATACCAAACGACGAGCGTGACACCACGATGCCTGTAGC
[1351] AATGGCAACAACGTTGCGCAAACTATTAACTGGCGAACTACTTACTCTAGCTTCC
[1352] CGGCAACAATTAATAGACTGGATGGAGGCGGATAAAGTTGCAGGACCACTTCTG
[1353] CGCTCGGCCCTTCCGGCTGGCTGGTTTATTGCTGATAAATCTGGAGCCGGTGAGC
[1354] GTGGGTCTCGCGGTATCATTGCAGCACTGGGGCCAGATGGTAAGCCCTCCCGTAT
[1355] CGTAGTTATCTACACGACGGGGAGTCAGGCAACTATGGATGAACGAAATAGACA
[1356] GATCGCTGAGATAGGTGCCTCACTGATTAAGCATTGGTAACTGTCAGACCAAGTT
[1357] TACTCATATATACTTTAGATTGATTTAAAACTTCATTTTTAATTTAAAAGGATCTA
[1358] GGTGAAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGT
[1359] TCCACTGAGCGTCAGACCCCGTAGAAAAGATCAAAGGATCTTCTTGAGATCCTTT
[1360] TTTTCTGCGCGTAATCTGCTGCTTGCAAACAAAAAAACCACCGCTACCAGCGGTG
[1361] GTTTGTTTGCCGGATCAAGAGCTACCAACTCTTTTTCCGAAGGTAACTGGCTTCA
[1362] GCAGAGCGCAGATACCAAATACTGTCCTTCTAGTGTAGCCGTAGTTAGGCCACCA
[1363] CTTCAAGAACTCTGTAGCACCGCCTACATACCTCGCTCTGCTAATCCTGTTACCA GTGGCTGCTGCCAGTGGCGATAAGTCGTGTCTTACCGGGTTGGACTCAAGACGAT
[1364] AGTTACCGGATAAGGCGCAGCGGTCGGGCTGAACGGGGGGTTCGTGCACACAGC
[1365] CCAGCTTGGAGCGAACGACCTACACCGAACTGAGATACCTACAGCGTGAGCTAT
[1366] GAGAAAGCGCCACGCTTCCCGAAGGGAGAAAGGCGGACAGGTATCCGGTAAGC
[1367] GGCAGGGTCGGAACAGGAGAGCGCACGAGGGAGCTTCCAGGGGGAAACGCCTG
[1368] GTATCTTTATAGTCCTGTCGGGTTTCGCCACCTCTGACTTGAGCGTCGATTTTTGT
[1369] GATGCTCGTCAGGGGGGCGGAGCCTATGGAAAAACGCCAGCAACGCGGCCTTTT
[1370] TACGGTTCCTGGCCTTTTGCTGGCCTTTTGCTCACATGGACTCTAGCTAGAGGATC
[1371] ACAGGCAGCAACGCTCTGTCATCGTTACAATCAACATGCTACCCTCCGCGAGATC
[1372] ATCCGTGTTTCAAACCCGGCAGCTTAGTTGCCGTTCTTCCGAATAGCATCGGTAA
[1373] CATGAGCAAAGTCTGCCGCCTTACAACGGCTCTCCCGCTGACGCCGTCCCGGACT
[1374] GATGGGCTGCCTGTATCGAGTGGTGATTTTGTGCCGAGCTGCCGGTCGGGGAGCT
[1375] GTTGGCTGGCTGGTGGCAGGATATATTGTGGTGTAAACAAATTGACGCTTAGACA
[1376] ACTTAATAACACATTGCGGACGTTTTTAATGATCGAATACTAACGTCTCTACCAG
[1377] ATATCAGCTTGCATGCCGGTCGATCTAGTAACATAGATGACACCGCGCGCGATAA
[1378] TTTATCCTAGTTTGCGCGCTATATTTTGTTTTCTATCGCGTATTAAATGTATAATTG
[1379] CGGGACTCTAATCATAAAAACCCATCTCATAAATAACGTCATGCATTACATGTTA
[1380] ATTATTACATGCTTAACGTAATTCAACAGAAATTATATGATAATCATCGCAAGAC
[1381] CGGCAACAGGATTCAATCTTAAGAAACTTTATTGCCAAATGTTTGAACGATCTGC
[1382] TTGACTCTAGCTAGAGTCCGAACCCCAGAGTCCCGCTCAGAAGAACTCGTCAAG
[1383] AAGGCGATAGAAGGCGATGCGCTGCGAATCGGGAGCGGCGATACCGTAAAGCA
[1384] CGAGGAAGCGGTCAGCCCATTCGCCGCCAAGCTCTTCAGCAATATCACGGGTAG
[1385] CCAACGCTATGTCCTGATAGCGGTCCGCCACACCCAGCCGGCCACAGTCGATGA
[1386] ATCCAGAAAAGCGGCCATTTTCCACCATGATATTCGGCAAGCAGGCATCGCCGTG
[1387] GGTCACGACGAGATCCTCGCCGTCGGGCATCCGCGCCTTGAGCCTGGCGAACAG
[1388] TTCGGCTGGCGCGAGCCCCTGATGCTCTTCGTCCAGATCATCCTGATCGACAAGA
[1389] CCGGCTTCCATCCGAGTACGTGCTCGCTCGATGCGATGTTTCGCTTGGTGGTCGA
[1390] ATGGGCAGGTAGCCGGATCAAGCGTATGCAGCCGCCGCATTGCATCAGCCATGA
[1391] TGGATACTTTCTCGGCAGGAGCAAGGTGAGATGACAGGAGATCCTGCCCCGGCA
[1392] CTTCGCCCAATAGCAGCCAGTTCCTTCCCGCTTCAGTGACAACGTCGAGCACAGC
[1393] TGCGCAAGGAACGCCCGTTGTGGCCAGCCACGATAGCCGCGCTGCCTCGTCTTGG
[1394] AGTTCATTCAGGGCACCGGACAGGTCGGTCTTGACAAAAAGAACCGGGCGCCCC
[1395] TGCGCTGACAGCCGGAACACGGCGGCATCAGAGCAGCCGATTGTTTGTTGTGCCC AGTCATAGCCGAATAGCCTCTCCACCCAAGCGGCCGGAGAACCTGCGTGCAATC
[1396] CATCTTGTTCAATCATGCCTGCATCGAGTTGAGAGTGAATATGAGACTCTAATTG
[1397] GATACCGAGGGGAATTTATGGAACGTCAGTGGAGCATTTTTGACAAGAAATATTT
[1398] GCTAGCTGATAGTGACCTTAGGCGACTTTTGAACGCGCAATAATGGTTTCTGACG
[1399] TATGTGCTTAGCTCATTAAACTCCAGAAACCCGCGGCTCAGTGGCTCCTTCAACG
[1400] TTGCGGTTCTGTCAGTTCCAAACGTAAAACGGCTTGTCCCGCGTCATCGGCGGGG
[1401] GTCATAACGTGACTCCCTTAATTCTCCGCTCATGATCGATATCCATTGAAGAGCA AGCT
[1402] 28. SEQ ID NO: 28 - pTRAkc-rbcsl-cTP L1:2C7 h4_s (Generation I)
[1403] AATTCCGCCCCTAGAAATATTTGCGACTCTTCTGGCATGTAATATTTCGTTAAATA
[1404] TGAAGTGCTCCATTTTTATTAACTTTAAATAATTGGTTGTACGATCACTTTCTTAT
[1405] CAAGCGTTACTAAAATGCGTCAATCTCTTTGTTCTTCCATATTCATATGTCAAAAT
[1406] CTATCAAAATTCTTATATATCTTTTTCGAATTTGAAGTGAAATTTCGATAATTTAA
[1407] AATTAAATAGAACATATCATTATTTAGGTGTCATATTGATTTTTATACTTAATTAC
[1408] TAAATTTGGTTAACTTTGAAAGTGTACATCAACGAAAAATTAGTCAAACGACTAA
[1409] AATAAATAAATATCATGTGTTATTAAGAAAATTCTCCTATAAGAATATTTTAATA
[1410] GATCATATGTTTGTAAAAAAAATTAATTTTTACTAACACATATATTTACTTATCAA
[1411] AAATTTGACAAAGTAAGATTAAAATAATATTCATCTAACAAAAAAAAACCAGAA
[1412] AATGCTGAAAACCCGGCAAAACCGAACCAATCCAAACCGATATAGTTGGTTTGG
[1413] TTTGATTTTGATATAAACCGAACCAACTCGGTCCATTTGCACCCCTAATCATAAT
[1414] AGCTTTAATATTTCAAGATATTATTAAGTTAACGTTGTCAATATCCTGGAAATTTT
[1415] GCAAAATGAATCAAGCCTATATGGCTGTAATATGAATTTAAAAGCAGCTCGATGT
[1416] GGTGGTAATATGTAATTTACTTGATTCTAAAAAAATATCCCAAGTATTAATAATT
[1417] TCTGCTAGGAAGAAGGTTAGCTACGATTTACAGCAAAGCCAGAATACAAAGAAC
[1418] CATAAAGTGATTGAAGCTCGAAATATACGAAGGAACAAATATTTTTAAAAAAAT
[1419] ACGCAATGACTTGGAACAAAAGAAAGTGATATATTTTTTGTTCTTAAACAAGCAT
[1420] CCCCTCTAAAGAATGGCAGTTTTCCTTTGCATGTAACTATTATGCTCCCTTCGTTA
[1421] CAAAAATTTTGGACTACTATTGGGCGCGGGGCGCGCCCGGTCCAAAGACCAGAG
[1422] GGCTATTGAGACTTTTCAACAAAGGGTAATATCGGGAAACCTCCTCGGATTCCAT
[1423] TGCCCAGCTATCTGTCACTTCATCGAAAGGACAGTAGAAAAGGAAGATGGCTTCT
[1424] ACAAATGCCATCATTGCGATAAAGGAAAGGCTATCGTTCAAGATGCCTCTACCG
[1425] ACAGTGGTCCCAAAGATGGACCCCCACCCACGAGGAACATCGTGGAAAAAGAAG ACGTTCCAACCACGTCTTCAAAGCAAGTGGATTGATGTGATACATGGTGGAGCAC
[1426] GACACTCTCGTCTACTCCAAGAATATCAAAGATACAGTCTCAGAAGACCAGAGG
[1427] GCTATTGAGACTTTTCAACAAAGGGTAATATCGGGAAACCTCCTCGGATTCCATT
[1428] GCCCAGCTATCTGTCACTTCATCGAAAGGACAGTAGAAAAGGAAGATGGCTTCT
[1429] ACAAATGCCATCATTGCGATAAAGGAAAGGCTATCGTTCAAGATGCCTCTACCG
[1430] ACAGTGGTCCCAAAGATGGACCCCCACCCACGAGGAACATCGTGGAAAAAGAAG
[1431] ACGTTCCAACCACGTCTTCAAAGCAAGTGGATTGATGTGATATCTCCACTGACGT
[1432] AAGGGATGACGCACAATCCCACTATCCTTCGCAAGACCCTTCCTCTATATAAGGA
[1433] AGTTCATTTCATTTGGAGAGGACACGCTGAATTCACAACACAAATCAGATTTATA
[1434] GAGAGATTTATAAAAAAAAAAAAAACAATGGCTTCCTCTGTTATTTCCTCTGCAG
[1435] CTGTTGCTACACGCACCAATGTTACACAAGCTGGCAGCATGATTGCACCTTTCAC
[1436] TGGTCTCAAATCTGCTGCTACTTTCCCTGTTTCAAGGAAGCAAAACCTTGACATC
[1437] ACTTCCATTGCTAGCAATGGTGGACGCGTTAGGTTCATGAGTCTGTGGCTGCCAT
[1438] CTGAGGCAACCGTGTACCTGCCACCTGTGCCTGTGAGCAAGGTGGTGTCCACCGA
[1439] TGAGTATGTGGCCCGGACAAATATCTACTATCACGCAGGCACATCCAGACTGCTG
[1440] GCAGTGGGCCACCCTTACTTCCCAATCAAGAAGCCTAACAATAACAAGATCCTG
[1441] GTGCCAAAGGTGTCCGGCCTGCAGTATAGGGTGTTCCGCATCCACCTGCCAGACC
[1442] CCAATAAGTTCGGCTTTCCAGACACCTCTTTTTACAACCCCGATACACAGAGGCT
[1443] GGTGTGGGCATGCGTGGGAGTGGAAGTGGGAAGGGGCCAGCCACTGGGCGTGG
[1444] GCATCTCCGGCCACCCCCTGCTGAATAAGCTGGACGATACCGAGAACGCCTCTGC
[1445] CTACGCAGCAAATGCAGGAGTGGACAACAGGGAGTGTATCAGCATGGATTATAA
[1446] GCAGACCCAGCTGTGCCTGATCGGCTGTAAGCCACCAATCGGAGAGCACTGGGG
[1447] CAAGGGATCTCCATGCACAAATGTGGCCGTGAACCCTGGCGATTGTCCTCCACTG
[1448] GAGCTGATCAATACCGTGATCCAGGACGGCGATATGGTGGACACAGGCTTCGGC
[1449] GCCATGGACTTCACCACCCTGCAGGCCAACAAGTCTGAGGTGCCTCTGGACATCT
[1450] GCACCAGCATCTGTAAGTACCCTGATTATATCAAGATGGTGAGCGAGCCATACG
[1451] GCGACTCCCTGTTCTTTTATCTGCGGAGAGAGCAGATGTTCGTGAGGCACCTGTT
[1452] TAATAGGGCAGGAGCAGTGGGAGAGAACGTGCCTGACGATCTGTACATCAAGGG
[1453] CTCCGGCTCTACCGCCAATCTGGCCAGCTCCAACTATTTCCCTACCCCAAGCGGC
[1454] TCCATGGTGACAAGCGATGCCCAGATCTTTAACAAGCCATATTGGCTGCAGAGG
[1455] GCCCAGGGCCACAATAACGGCATCTGCTGGGGCAATCAGCTGTTCGTGACCGTG
[1456] GTGGACACCACACGCTCTACAAACATGAGCCTGTGCGCCGCCATCTCTACCAGCG
[1457] AGACCACATACAAGAACACAAACTTTAAGGAGTACCTGAGGCACGGCGAGGAGT ATGACCTGCAGTTCATCTTTCAGCTGTGCAAGATCACCCTGACAGCCGATGTGAT
[1458] GACCTACATCCACTCCATGAACAGCACAATCCTGGAGGACTGGAACTTCGGCCTG
[1459] CAGCCACCTCCAGGAGGAACCTGCGGACCCATCCCTGTGCTGGATGAGAATGGA
[1460] CTGTTTGCACCAGGACCATGTACCCCACCTGCACCAAAGGAGGACCCTCTGAAG
[1461] AAGTACACATTCTGGGAGGTGAACCTGAAGGAGAAGTTTAGCGCCGACCTGGAT
[1462] CAGTTCCCACTGGGACGGAAGTTTCTGCTGCAGGCCGGCCTGAAGGCCAAGCCA
[1463] AAGTTCACCCTGGGCAAGAGAAAGGCCACCCCCACCACATCTAGCACATCCACC
[1464] ACAGCCAAGCGGAAGAAGAGAAAGCTGTAAGGATCCCTCGAGCTCGGATCCTCT
[1465] AGAGTCCGCAAAAATCACCAGTCTCTCTCTACAAATCTATCTCTCTCTATTTTTCT
[1466] CCAGAATAATGTGTGAGTAGTTCCCAGATAAGGGAATTAGGGTTCTTATAGGGTT
[1467] TCGCTCATGTGTTGAGCATATAAGAAACCCTTAGTATGTATTTGTATTTGTAAAAT
[1468] ACTTCTATCAATAAAATTTCTAATTCCTAAAACCAAAATCCAGTGACCGGGCGGC
[1469] CGGCCGCCCCTAGAAATATTTGCGACTCTTCTGGCATGTAATATTTCGTTAAATAT
[1470] GAAGTGCTCCATTTTTATTAACTTTAAATAATTGGTTGTACGATCACTTTCTTATC
[1471] AAGCGTTACTAAAATGCGTCAATCTCTTTGTTCTTCCATATTCATATGTCAAAATC
[1472] TATCAAAATTCTTATATATCTTTTTCGAATTTGAAGTGAAATTTCGATAATTTAAA
[1473] ATTAAATAGAACATATCATTATTTAGGTGTCATATTGATTTTTATACTTAATTACT
[1474] AAATTTGGTTAACTTTGAAAGTGTACATCAACGAAAAATTAGTCAAACGACTAA
[1475] AATAAATAAATATCATGTGTTATTAAGAAAATTCTCCTATAAGAATATTTTAATA
[1476] GATCATATGTTTGTAAAAAAAATTAATTTTTACTAACACATATATTTACTTATCAA
[1477] AAATTTGACAAAGTAAGATTAAAATAATATTCATCTAACAAAAAAAAACCAGAA
[1478] AATGCTGAAAACCCGGCAAAACCGAACCAATCCAAACCGATATAGTTGGTTTGG
[1479] TTTGATTTTGATATAAACCGAACCAACTCGGTCCATTTGCACCCCTAATCATAAT
[1480] AGCTTTAATATTTCAAGATATTATTAAGTTAACGTTGTCAATATCCTGGAAATTTT
[1481] GCAAAATGAATCAAGCCTATATGGCTGTAATATGAATTTAAAAGCAGCTCGATGT
[1482] GGTGGTAATATGTAATTTACTTGATTCTAAAAAAATATCCCAAGTATTAATAATT
[1483] TCTGCTAGGAAGAAGGTTAGCTACGATTTACAGCAAAGCCAGAATACAAAGAAC
[1484] CATAAAGTGATTGAAGCTCGAAATATACGAAGGAACAAATATTTTTAAAAAAAT
[1485] ACGCAATGACTTGGAACAAAAGAAAGTGATATATTTTTTGTTCTTAAACAAGCAT
[1486] CCCCTCTAAAGAATGGCAGTTTTCCTTTGCATGTAACTATTATGCTCCCTTCGTTA
[1487] CAAAAATTTTGGACTACTATTGGGCGGGTGGAGGGGGATCAGATTGTCGTTTCCC
[1488] GCCTTCAGTTTAAACTATCAGTGTTTGACAGGATATATTGGCGGGTAAACCTAAG
[1489] AGAAAAGAGCGTTTATTAGAATAATCGGATATTTAAAAGGGCGTGAAAAGGTTT ATCCGTTCGTCCATTTGTATGTGTACATCACCGACGAGCAAGGCAAGACCGAGCG
[1490] CCTTTCCGACGCTCACCGGGCTGGTTGCCCTCGCCGCTGGGCTGGCGGCCGTCTA
[1491] TGGCCCTGCAAACGCGCCAGAAACGCCGTCGAAGCCGTGTGCGAGACACCGGCC
[1492] GCCGGCGTTGTGGATACCTCGCGGAAAACTTGGCCCTCACTGACAGATGAGGGG
[1493] CGGACGTTGACACTTGAGGGGCCGACTCACCCGGCGCGGCGTTGACAGATGAGG
[1494] GGCAGGCTCGATTTCGGCCGGCGACGTGGAGCTGGCCAGCCTCGCAAATCGGCG
[1495] AAAACGCCTGATTTTACGCGAGTTTCCCACAGATGATGTGGACAAGCCTGGGGAT
[1496] AAGTGCCCTGCGGTATTGACACTTGAGGGGCGCGACTACTGACAGATGAGGGGC
[1497] GCGATCCTTGACACTTGAGGGGCAGAGTGCTGACAGATGAGGGGCGCACCTATT
[1498] GACATTTGAGGGGCTGTCCACAGGCAGAAAATCCAGCATTTGCAAGGGTTTCCG
[1499] CCCGTTTTTCGGCCACCGCTAACCTGTCTTTTAACCTGCTTTTAAACCAATATTTA
[1500] TAAACCTTGTTTTTAACCAGGGCTGCGCCCTGTGCGCGTGACCGCGCACGCCGAA
[1501] GGGGGGTGCCCCCCCTTCTCGAACCCTCCCGGCCCGCTAACGCGGGCCTCCCATC
[1502] CCCCCAGGGGCTGCGCCCCTCGGCCGCGAACGGCCTCACCCCAAAAATGGCAGC
[1503] GCTGGCAGTCCTTGCCATTGCCGGGATCGGGGCAGTAACGGGATGGGCGATCAG
[1504] CCCGACAAGCTACCCCTATTTGTTTATTTTTCTAAATACATTCAAATATGTATCCG
[1505] CTCATGAGACAATAACCCTGATAAATGCTTCAATAATATTGAAAAAGGAAGAGT
[1506] ATGAGTATTCAACATTTCCGTGTCGCCCTTATTCCCTTTTTTGCGGCATTTTGCCTT
[1507] CCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTAAAAGATGCTGAAGATCAGT
[1508] TGGGTGCACGAGTGGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTG
[1509] AGAGTTTTCGCCCCGAAGAACGTTTTCCAATGATGAGCACTTTTAAAGTTCTGCT
[1510] ATGTGGCGCGGTATTATCCCGTATTGACGCCGGGCAAGAGCAACTCGGTCGCCGC
[1511] ATACACTATTCTCAGAATGACTTGGTTGAGTACTCACCAGTCACAGAAAAGCATC
[1512] TTACGGATGGCATGACAGTAAGAGAATTATGCAGTGCTGCCATAACCATGAGTG
[1513] ATAACACTGCGGCCAACTTACTTCTGACAACGATCGGAGGACCGAAGGAGCTAA
[1514] CCGCTTTTTTGCACAACATGGGGGATCATGTAACTCGCCTTGATCGTTGGGAACC
[1515] GGAGCTGAATGAAGCCATACCAAACGACGAGCGTGACACCACGATGCCTGTAGC
[1516] AATGGCAACAACGTTGCGCAAACTATTAACTGGCGAACTACTTACTCTAGCTTCC
[1517] CGGCAACAATTAATAGACTGGATGGAGGCGGATAAAGTTGCAGGACCACTTCTG
[1518] CGCTCGGCCCTTCCGGCTGGCTGGTTTATTGCTGATAAATCTGGAGCCGGTGAGC
[1519] GTGGGTCTCGCGGTATCATTGCAGCACTGGGGCCAGATGGTAAGCCCTCCCGTAT
[1520] CGTAGTTATCTACACGACGGGGAGTCAGGCAACTATGGATGAACGAAATAGACA
[1521] GATCGCTGAGATAGGTGCCTCACTGATTAAGCATTGGTAACTGTCAGACCAAGTT TACTCATATATACTTTAGATTGATTTAAAACTTCATTTTTAATTTAAAAGGATCTA
[1522] GGTGAAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGT
[1523] TCCACTGAGCGTCAGACCCCGTAGAAAAGATCAAAGGATCTTCTTGAGATCCTTT
[1524] TTTTCTGCGCGTAATCTGCTGCTTGCAAACAAAAAAACCACCGCTACCAGCGGTG
[1525] GTTTGTTTGCCGGATCAAGAGCTACCAACTCTTTTTCCGAAGGTAACTGGCTTCA
[1526] GCAGAGCGCAGATACCAAATACTGTCCTTCTAGTGTAGCCGTAGTTAGGCCACCA
[1527] CTTCAAGAACTCTGTAGCACCGCCTACATACCTCGCTCTGCTAATCCTGTTACCA
[1528] GTGGCTGCTGCCAGTGGCGATAAGTCGTGTCTTACCGGGTTGGACTCAAGACGAT
[1529] AGTTACCGGATAAGGCGCAGCGGTCGGGCTGAACGGGGGGTTCGTGCACACAGC
[1530] CCAGCTTGGAGCGAACGACCTACACCGAACTGAGATACCTACAGCGTGAGCTAT
[1531] GAGAAAGCGCCACGCTTCCCGAAGGGAGAAAGGCGGACAGGTATCCGGTAAGC
[1532] GGCAGGGTCGGAACAGGAGAGCGCACGAGGGAGCTTCCAGGGGGAAACGCCTG
[1533] GTATCTTTATAGTCCTGTCGGGTTTCGCCACCTCTGACTTGAGCGTCGATTTTTGT
[1534] GATGCTCGTCAGGGGGGCGGAGCCTATGGAAAAACGCCAGCAACGCGGCCTTTT
[1535] TACGGTTCCTGGCCTTTTGCTGGCCTTTTGCTCACATGGACTCTAGCTAGAGGATC
[1536] ACAGGCAGCAACGCTCTGTCATCGTTACAATCAACATGCTACCCTCCGCGAGATC
[1537] ATCCGTGTTTCAAACCCGGCAGCTTAGTTGCCGTTCTTCCGAATAGCATCGGTAA
[1538] CATGAGCAAAGTCTGCCGCCTTACAACGGCTCTCCCGCTGACGCCGTCCCGGACT
[1539] GATGGGCTGCCTGTATCGAGTGGTGATTTTGTGCCGAGCTGCCGGTCGGGGAGCT
[1540] GTTGGCTGGCTGGTGGCAGGATATATTGTGGTGTAAACAAATTGACGCTTAGACA
[1541] ACTTAATAACACATTGCGGACGTTTTTAATGATCGAATACTAACGTCTCTACCAG
[1542] ATATCAGCTTGCATGCCGGTCGATCTAGTAACATAGATGACACCGCGCGCGATAA
[1543] TTTATCCTAGTTTGCGCGCTATATTTTGTTTTCTATCGCGTATTAAATGTATAATTG
[1544] CGGGACTCTAATCATAAAAACCCATCTCATAAATAACGTCATGCATTACATGTTA
[1545] ATTATTACATGCTTAACGTAATTCAACAGAAATTATATGATAATCATCGCAAGAC
[1546] CGGCAACAGGATTCAATCTTAAGAAACTTTATTGCCAAATGTTTGAACGATCTGC
[1547] TTGACTCTAGCTAGAGTCCGAACCCCAGAGTCCCGCTCAGAAGAACTCGTCAAG
[1548] AAGGCGATAGAAGGCGATGCGCTGCGAATCGGGAGCGGCGATACCGTAAAGCA
[1549] CGAGGAAGCGGTCAGCCCATTCGCCGCCAAGCTCTTCAGCAATATCACGGGTAG
[1550] CCAACGCTATGTCCTGATAGCGGTCCGCCACACCCAGCCGGCCACAGTCGATGA
[1551] ATCCAGAAAAGCGGCCATTTTCCACCATGATATTCGGCAAGCAGGCATCGCCGTG
[1552] GGTCACGACGAGATCCTCGCCGTCGGGCATCCGCGCCTTGAGCCTGGCGAACAG
[1553] TTCGGCTGGCGCGAGCCCCTGATGCTCTTCGTCCAGATCATCCTGATCGACAAGA CCGGCTTCCATCCGAGTACGTGCTCGCTCGATGCGATGTTTCGCTTGGTGGTCGA
[1554] ATGGGCAGGTAGCCGGATCAAGCGTATGCAGCCGCCGCATTGCATCAGCCATGA
[1555] TGGATACTTTCTCGGCAGGAGCAAGGTGAGATGACAGGAGATCCTGCCCCGGCA
[1556] CTTCGCCCAATAGCAGCCAGTTCCTTCCCGCTTCAGTGACAACGTCGAGCACAGC
[1557] TGCGCAAGGAACGCCCGTTGTGGCCAGCCACGATAGCCGCGCTGCCTCGTCTTGG
[1558] AGTTCATTCAGGGCACCGGACAGGTCGGTCTTGACAAAAAGAACCGGGCGCCCC
[1559] TGCGCTGACAGCCGGAACACGGCGGCATCAGAGCAGCCGATTGTTTGTTGTGCCC
[1560] AGTCATAGCCGAATAGCCTCTCCACCCAAGCGGCCGGAGAACCTGCGTGCAATC
[1561] CATCTTGTTCAATCATGCCTGCATCGAGTTGAGAGTGAATATGAGACTCTAATTG
[1562] GATACCGAGGGGAATTTATGGAACGTCAGTGGAGCATTTTTGACAAGAAATATTT
[1563] GCTAGCTGATAGTGACCTTAGGCGACTTTTGAACGCGCAATAATGGTTTCTGACG
[1564] TATGTGCTTAGCTCATTAAACTCCAGAAACCCGCGGCTCAGTGGCTCCTTCAACG
[1565] TTGCGGTTCTGTCAGTTCCAAACGTAAAACGGCTTGTCCCGCGTCATCGGCGGGG
[1566] GTCATAACGTGACTCCCTTAATTCTCCGCTCATGATCGATATCCATTGAAGAGCA AGCT
[1567] 29. SEQ ID NO: 29 - pRIC3 LI :2C7 DE_i (Generation I)
[1568] GAAGAGCGTGACTCCGAGGGGTTGCCTCAAACTCTATCTTATAACCGGCGTGGA
[1569] GGCATGGAGGCAGGGGTATTTTGGTCATTTTAATAGATAGTGGAAAATGACGTG
[1570] GAATTTACTTAAAGACGAAGTCTTTGCGACAAGGGGGGGCCCACGCCGAATTTA
[1571] ATATTACCGGCGTGGCCCCCCCTTATCGCGAGTGCTTTAGCACGAGCGGTCCAGA
[1572] TTTAAAGTAGAAAATTTCCCGCCCACTAGGGTTAAAGGTGTTCACACTATAAAAG
[1573] CATATACGATGTGATGGTATTTGCTCGACCTGGTCCAAAGACCAGAGGGCTATTG
[1574] AGACTTTTCAACAAAGGGTAATATCGGGAAACCTCCTCGGATTCCATTGCCCAGC
[1575] TATCTGTCACTTCATCGAAAGGACAGTAGAAAAGGAAGATGGCTTCTACAAATG
[1576] CCATCATTGCGATAAAGGAAAGGCTATCGTTCAAGATGCCTCTACCGACAGTGGT
[1577] CCCAAAGATGGACCCCCACCCACGAGGAACATCGTGGAAAAAGAAGACGTTCCA
[1578] ACCACGTCTTCAAAGCAAGTGGATTGATGTGATACATGGTGGAGCACGACACTCT
[1579] CGTCTACTCCAAGAATATCAAAGATACAGTCTCAGAAGACCAGAGGGCTATTGA
[1580] GACTTTTCAACAAAGGGTAATATCGGGAAACCTCCTCGGATTCCATTGCCCAGCT
[1581] ATCTGTCACTTCATCGAAAGGACAGTAGAAAAGGAAGATGGCTTCTACAAATGC
[1582] CATCATTGCGATAAAGGAAAGGCTATCGTTCAAGATGCCTCTACCGACAGTGGTC
[1583] CCAAAGATGGACCCCCACCCACGAGGAACATCGTGGAAAAAGAAGACGTTCCAA CCACGTCTTCAAAGCAAGTGGATTGATGTGATATCTCCACTGACGTAAGGGATGA
[1584] CGCACAATCCCACTATCCTTCGCAAGACCCTTCCTCTATATAAGGAAGTTCATTTC
[1585] ATTTGGAGAGGACACGCTGAGTTCACAACACAAATCAGATTTATAGAGAGATTT
[1586] ATAAAAAAAAAAAAACATGAGTCTGTGGCTGCCATCTGAGGCAACCGTGTACCT
[1587] GCCACCTGTGCCTGTGAGCAAGGTGGTGTCCACCGACGAGTATGTGGCCCGGAC
[1588] AAATATCTACTATCACGCAGGCACAAGCAGACTGCTGGCAGTGGGCCACCCTTA
[1589] CTTCCCAATCAAGAAGCCTAACAATAACAAGATCCTGGTGCCAAAGGTGAGCGG
[1590] CCTGCAGTATAGGGTGTTCCGCATCCACCTGCCAGATCCCAATAAGTTCGGCTTT
[1591] CCAGACACCTCCTTTTACAACCCCGATACACAGAGGCTGGTGTGGGCATGCGTGG
[1592] GAGTGGAAGTGGGAAGGGGCCAGCCACTGGGCGTGGGCATCTCCGGCCACCCCC
[1593] TGCTGAATAAGCTGGACGATACCGAGAACTGTGGCCCTATCCCAGTGCTGGACG
[1594] AGAACGGACTGTTTGCACCAGGACCTTGCGCATCCGCCTACGCAGCAAATGCAG
[1595] GAGTGGACAACAGGGAGTGTATCTCTATGGATTATAAGCAGACCCAGCTGTGCC
[1596] TGATCGGCTGTAAGCCACCAATCGGAGAGCACTGGGGCAAGGGATCTCCATGCA
[1597] CAAATGTGGCCGTGAACCCTGGCGACTGTCCTCCACTGGAGCTGATCAATACCGT
[1598] GATCCAGGACGGCGATATGGTGGACACAGGCTTCGGCGCCATGGACTTCACCAC
[1599] CCTGCAGGCCAACAAGTCTGAGGTGCCTCTGGACATCTGCACCAGCATCTGTAAG
[1600] TACCCTGATTATATCAAGATGGTGAGCGAGCCATACGGCGATTCCCTGTTCTTTT
[1601] ATCTGCGGAGAGAGCAGATGTTCGTGAGGCACCTGTTTAATAGGGCAGGAGCAG
[1602] TGGGAGAGAACGTGCCTGACGATCTGTACATCAAGGGCTCCGGCTCTACCGCCA
[1603] ATCTGGCCAGCTCCAACTATTTCCCAACCCCCAGCGGCTCCATGGTGACAAGCGA
[1604] CGCCCAGATCTTTAATAAGCCATACTGGCTGCAGAGGGCCCAGGGCCACAATAA
[1605] CGGCATCTGCTGGGGCAATCAGCTGTTCGTGACCGTGGTGGATACCACACGCTCT
[1606] ACAAACATGAGCCTGTGCGCCGCCATCTCTACCAGCGAGACCACATACAAGAAC
[1607] ACAAACTTTAAGGAGTACCTGCGGCACGGCGAGGAGTATGACCTGCAGTTCATC
[1608] TTTCAGCTGTGCAAGATCACCCTGACAGCCGATGTGATGACCTACATCCACTCCA
[1609] TGAACAGCACAATCCTGGAGGACTGGAACTTCGGACTGCAGCCACCTCCAGGAG
[1610] GCACCCTGGAGGATACATATAGGTTTGTGACCTCTCAGGCCATCGCCTGTCAGAA
[1611] GCACACACCACCTGCACCAAAGGAGGACCCTCTGAAGAAGTACACCTTCTGGGA
[1612] GGTGAACCTGAAGGAGAAGTTTAGCGCCGACCTGGATCAGTTCCCACTGGGACG
[1613] GAAGTTTCTGCTGCAGGCCGGCCTGAAGGCCAAGCCAAAGTTCACCCTGGGCAA
[1614] GAGAAAGGCCACCCCCACCACATCTAGCACATCCACCACAGCCAAGCGGAAGAA
[1615] GAGAAAGCTGTAAGGATCCCTCGAGCTCTCTAGAGTCCGCAAAAATCACCAGTC TCTCTCTACAAATCTATCTCTCTCTATTTTTCTCCAGAATAATGTGTGAGTAGTTC
[1616] CCAGATAAGGGAATTAGGGTTCTTATAGGGTTTCGCTCATGTGTTGAGCATATAA
[1617] GAAACCCTTAGTATGTATTTGTATTTGTAAAATACTTCTATCAATAAAATTTCTAA
[1618] TTCCTAAAACCAAAATCCAGTGACCGGGCGGCGGGTCGAGAATGATTATTTTATG
[1619] AATATATTTCATTGTGCAAGTAGATAGAAATTACATATGTTACATAACACACGAA
[1620] ATAAACAAAAAAAGACAATCCAAAAACAAACACCCCAAAAAAAATAATCACTTT
[1621] AGATAAACTCGTATGAGGAGAGGCACGTTCAGTGACTCGACGATTCCCGAGCAA
[1622] AAAAAGTCTCCCCGTCACACATATAGTGGGTGACGCAATTATCTTTAAAGTAATC
[1623] CTTCTGTTGACTTGTCATTGATAACATCCAGTCTTCGTCAGGATTGCAAAGAATTA
[1624] TAGAAGGGATCCCACCTTTTATTTTCTTCTTTTTTCCATATTTAGGGTTGACAGTG
[1625] AAATCAGACTGGCAACCTATTAATTGCTTCCACAATGGGACGAACTTGAAGGGG
[1626] ATGTCGTCGATGATATTATAGGTGGCGTGTTCATCGTAGTTGGTGAAATCGATGG
[1627] TACCGTTCCAATAGTTGTGTCGTCCGAGACTTCTAGCCCAGGTGGTCTTTCCGGTA
[1628] CGAGTTGGTCCGCAGATGTAGAGGCTGGGGTGTCGGATTCCATTCCTTCCATTGT
[1629] CCTGGTTAAATCGGCCATCCATTCAAGGTCAGATTGAGCTTGTTGGTATGAGACA
[1630] GGATGTATGTAAGTATAAGCGTCTATGCTTACATGGTATAGATGGGTTTCCCTCC
[1631] AGGAGTGTAGATCTTCGTGGCAGCGAAGATCTGATTCTGTGAAGGGCGACACAT
[1632] ACGGTTCAGGTTGTGGAGGGAATAATTTGTTGGCTGAATATTCCAGCCATTGAAG
[1633] TTTTGTTGCCCATTCATGAGGGAATTCTTCCTTGATCATGTCAAGATATTCCTCCT
[1634] TAGACGTTGCAGTCTGGATAATAGTTCTCCATCGTGCGTCAGATTTGCGAGGAGA
[1635] GACCTTATGATCTCGGAAATCTCCTCTGGTTTTAATATCTCCGTCCTTTGATATGT
[1636] AATCAAGGACTTGTTTAGAGTTTCTAGCTGGCTGGATATTAGGGTGATTTCCTTC
[1637] AAAATCGAAAAAAGAAGGATCCCTAATACAAGGTTTTTTATCAAGCTGGAGAAG
[1638] AGCATGATAGTGGGTAGTGCCATCTTGATGAAGCTCAGAAGCAACACCAAGGAA
[1639] GAAAATAAGAAAAGGTGTGAGTTTCTCCCAGAGAAACTGGAATAAATCATCTCT
[1640] TTGAGATGAGCACTTGGGATAGGTAAGGAAAACATATTTAGATTGGAGTCTGAA
[1641] GTTCTTACTAGCAGAAGGCATGTTGTTGTGACTCCGAGGGGTTGCCTCAAACTCT
[1642] ATCTTATAACCGGCGTGGAGGCATGGAGGCAGGGGTATTTTGGTCATTTTAATAG
[1643] ATAGTGGAAAATGACGTGGAATTTACTTAAAGACGAAGTCTTTGCGACAAGGGG
[1644] GGGCCCACGCCGAATTTAATATTACCGGCGTGGCCCCCCCTTATCGCGAGTGCTT
[1645] TAGCACGAGCGGTCCAGATTTAAAGTAGAAAATTTCCCGCCCACTAGGGTTAAA
[1646] GGTGTTCACACTATACAAGCATATACGATGTGATGGTATTGACTAGAGTTTAAAC
[1647] TATCAGTGTTTGACAGGATATATTGGCGGGTAAACCTAAGAGAAAAGAGCGTTT ATTAGAATAATCGGATATTTAAAAGGGCGTGAAAAGGTTTATCCGTTCGTCCATT
[1648] TGTATGTGTACATCACCGACGAGCAAGGCAAGACCGAGCGCCTTTCCGACGCTC
[1649] ACCGGGCTGGTTGCCCTCGCCGCTGGGCTGGCGGCCGTCTATGGCCCTGCAAACG
[1650] CGCCAGAAACGCCGTCGAAGCCGTGTGCGAGACACCGGCCGCCGGCGTTGTGGA
[1651] TACCTCGCGGAAAACTTGGCCCTCACTGACAGATGAGGGGCGGACGTTGACACT
[1652] TGAGGGGCCGACTCACCCGGCGCGGCGTTGACAGATGAGGGGCAGGCTCGATTT
[1653] CGGCCGGCGACGTGGAGCTGGCCAGCCTCGCAAATCGGCGAAAACGCCTGATTT
[1654] TACGCGAGTTTCCCACAGATGATGTGGACAAGCCTGGGGATAAGTGCCCTGCGG
[1655] TATTGACACTTGAGGGGCGCGACTACTGACAGATGAGGGGCGCGATCCTTGACA
[1656] CTTGAGGGGCAGAGTGCTGACAGATGAGGGGCGCACCTATTGACATTTGAGGGG
[1657] CTGTCCACAGGCAGAAAATCCAGCATTTGCAAGGGTTTCCGCCCGTTTTTCGGCC
[1658] ACCGCTAACCTGTCTTTTAACCTGCTTTTAAACCAATATTTATAAACCTTGTTTTT
[1659] AACCAGGGCTGCGCCCTGTGCGCGTGACCGCGCACGCCGAAGGGGGGTGCCCCC
[1660] CCTTCTCGAACCCTCCCGGCCCGCTAACGCGGGCCTCCCATCCCCCCAGGGGCTG
[1661] CGCCCCTCGGCCGCGAACGGCCTCACCCCAAAAATGGCAGCGCTGGCAGTCCTT
[1662] GCCATTGCCGGGATCGGGGCAGTAACGGGATGGGCGATCAGCCCGAAAGCTACC
[1663] CCTATTTGTTTATTTTTCTAAATACATTCAAATATGTATCCGCTCATGAGACAATA
[1664] ACCCTGATAAATGCTTCAATAATATTGAAAAAGGAAGAGTATGAGTATTCAACA
[1665] TTTCCGTGTCGCCCTTATTCCCTTTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCA
[1666] CCCAGAAACGCTGGTGAAAGTAAAAGATGCTGAAGATCAGTTGGGTGCACGAGT
[1667] GGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTGAGAGTTTTCGCCCC
[1668] GAAGAACGTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTAT
[1669] TATCCCGTATTGACGCCGGGCAAGAGCAACTCGGTCGCCGCATACACTATTCTCA
[1670] GAATGACTTGGTTGAGTACTCACCAGTCACAGAAAAGCATCTTACGGATGGCAT
[1671] GACAGTAAGAGAATTATGCAGTGCTGCCATAACCATGAGTGATAACACTGCGGC
[1672] CAACTTACTTCTGACAACGATCGGAGGACCGAAGGAGCTAACCGCTTTTTTGCAC
[1673] AACATGGGGGATCATGTAACTCGCCTTGATCGTTGGGAACCGGAGCTGAATGAA
[1674] GCCATACCAAACGACGAGCGTGACACCACGATGCCTGTAGCAATGGCAACAACG
[1675] TTGCGCAAACTATTAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAATTAA
[1676] TAGACTGGATGGAGGCGGATAAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTCC
[1677] GGCTGGCTGGTTTATTGCTGATAAATCTGGAGCCGGTGAGCGTGGGTCTCGCGGT
[1678] ATCATTGCAGCACTGGGGCCAGATGGTAAGCCCTCCCGTATCGTAGTTATCTACA
[1679] CGACGGGGAGTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGAGATAG GTGCCTCACTGATTAAGCATTGGTAACTGTCAGACCAAGTTTACTCATATATACT
[1680] TTAGATTGATTTAAAACTTCATTTTTAATTTAAAAGGATCTAGGTGAAGATCCTTT
[1681] TTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGTTCCACTGAGCGTC
[1682] AGACCCCGTAGAAAAGATCAAAGGATCTTCTTGAGATCCTTTTTTTCTGCGCGTA
[1683] ATCTGCTGCTTGCAAACAAAAAAACCACCGCTACCAGCGGTGGTTTGTTTGCCGG
[1684] ATCAAGAGCTACCAACTCTTTTTCCGAAGGTAACTGGCTTCAGCAGAGCGCAGAT
[1685] ACCAAATACTGTTCTTCTAGTGTAGCCGTAGTTAGGCCACCACTTCAAGAACTCT
[1686] GTAGCACCGCCTACATACCTCGCTCTGCTAATCCTGTTACCAGTGGCTGCTGCCA
[1687] GTGGCGATAAGTCGTGTCTTACCGGGTTGGACTCAAGACGATAGTTACCGGATAA
[1688] GGCGCAGCGGTCGGGCTGAACGGGGGGTTCGTGCACACAGCCCAGCTTGGAGCG
[1689] AACGACCTACACCGAACTGAGATACCTACAGCGTGAGCTATGAGAAAGCGCCAC
[1690] GCTTCCCGAAGGGAGAAAGGCGGACAGGTATCCGGTAAGCGGCAGGGTCGGAA
[1691] CAGGAGAGCGCACGAGGGAGCTTCCAGGGGGAAACGCCTGGTATCTTTATAGTC
[1692] CTGTCGGGTTTCGCCACCTCTGACTTGAGCGTCGATTTTTGTGATGCTCGTCAGGG
[1693] GGGCGGAGCCTATGGAAAAACGCCAGCAACGCGGCCTTTTTACGGTTCCTGGCCT
[1694] TTTGCTGGCCTTTTGCTCACATGGACTCTAGCTAGAGGATCACAGGCAGCAACGC
[1695] TCTGTCATCGTTACAATCAACATGCTACCCTCCGCGAGATCATCCGTGTTTCAAA
[1696] CCCGGCAGCTTAGTTGCCGTTCTTCCGAATAGCATCGGTAACATGAGCAAAGTCT
[1697] GCCGCCTTACAACGGCTCTCCCGCTGACGCCGTCCCGGACTGATGGGCTGCCTGT
[1698] ATCGAGTGGTGATTTTGTGCCGAGCTGCCGGTCGGGGAGCTGTTGGCTGGCTGGT
[1699] GGCAGGATATATTGTGGTGTAAACAAATTGACGCTTAGACAACTTAATAACACAT
[1700] TGCGGACGTTTTTAATGATCGAATACTAACGTCTCTACCACATT
[1701] 30. SEQ ID NO: 30 - pRIC3 LI :2C7 DE_s (Generation I)
[1702] GAAGAGCGTGACTCCGAGGGGTTGCCTCAAACTCTATCTTATAACCGGCGTGGA
[1703] GGCATGGAGGCAGGGGTATTTTGGTCATTTTAATAGATAGTGGAAAATGACGTG
[1704] GAATTTACTTAAAGACGAAGTCTTTGCGACAAGGGGGGGCCCACGCCGAATTTA
[1705] ATATTACCGGCGTGGCCCCCCCTTATCGCGAGTGCTTTAGCACGAGCGGTCCAGA
[1706] TTTAAAGTAGAAAATTTCCCGCCCACTAGGGTTAAAGGTGTTCACACTATAAAAG
[1707] CATATACGATGTGATGGTATTTGCTCGACCTGGTCCAAAGACCAGAGGGCTATTG
[1708] AGACTTTTCAACAAAGGGTAATATCGGGAAACCTCCTCGGATTCCATTGCCCAGC
[1709] TATCTGTCACTTCATCGAAAGGACAGTAGAAAAGGAAGATGGCTTCTACAAATG
[1710] CCATCATTGCGATAAAGGAAAGGCTATCGTTCAAGATGCCTCTACCGACAGTGGT CCCAAAGATGGACCCCCACCCACGAGGAACATCGTGGAAAAAGAAGACGTTCCA
[1711] ACCACGTCTTCAAAGCAAGTGGATTGATGTGATACATGGTGGAGCACGACACTCT
[1712] CGTCTACTCCAAGAATATCAAAGATACAGTCTCAGAAGACCAGAGGGCTATTGA
[1713] GACTTTTCAACAAAGGGTAATATCGGGAAACCTCCTCGGATTCCATTGCCCAGCT
[1714] ATCTGTCACTTCATCGAAAGGACAGTAGAAAAGGAAGATGGCTTCTACAAATGC
[1715] CATCATTGCGATAAAGGAAAGGCTATCGTTCAAGATGCCTCTACCGACAGTGGTC
[1716] CCAAAGATGGACCCCCACCCACGAGGAACATCGTGGAAAAAGAAGACGTTCCAA
[1717] CCACGTCTTCAAAGCAAGTGGATTGATGTGATATCTCCACTGACGTAAGGGATGA
[1718] CGCACAATCCCACTATCCTTCGCAAGACCCTTCCTCTATATAAGGAAGTTCATTTC
[1719] ATTTGGAGAGGACACGCTGAGTTCACAACACAAATCAGATTTATAGAGAGATTT
[1720] ATAAAAAAAAAAAAACATGAGTCTGTGGCTGCCATCTGAGGCAACCGTGTACCT
[1721] GCCACCTGTGCCTGTGAGCAAGGTGGTGTCCACCGACGAGTATGTGGCCCGGAC
[1722] AAACATCTACTATCACGCAGGCACAAGCAGACTGCTGGCAGTGGGCCACCCTTA
[1723] CTTCCCAATCAAGAAGCCTAACAATAACAAGATCCTGGTGCCAAAGGTGTCCGG
[1724] CCTGCAGTATAGGGTGTTCCGCATCCACCTGCCAGATCCCAATAAGTTCGGCTTT
[1725] CCAGACACCTCTTTTTACAACCCCGATACACAGAGGCTGGTGTGGGCATGCGTGG
[1726] GAGTGGAAGTGGGAAGGGGCCAGCCACTGGGAGTGGGAATCTCTGGACACCCAC
[1727] TGCTGAATAAGCTGGACGATACCGAGTGCGGCCCTATCCCAGTGCTGGACGAGA
[1728] ACGGACTGTTTGCACCAGGACCTTGTATGGATTATAAGCAGACCCAGCTGTGCCT
[1729] GATCGGCTGTAAGCCACCAATCGGAGAGCACTGGGGCAAGGGATCCCCATGCAC
[1730] AAATGTGGCCGTGAACCCTGGCGACTGTCCTCCACTGGAGCTGATCAATACCGTG
[1731] ATCCAGGACGGCGATATGGTGGACACAGGCTTCGGCGCCATGGACTTCACCACC
[1732] CTGCAGGCCAACAAGTCTGAGGTGCCTCTGGACATCTGCACCAGCATCTGTAAGT
[1733] ACCCTGATTATATCAAGATGGTGAGCGAGCCATACGGCGATTCCCTGTTCTTTTA
[1734] TCTGCGGAGAGAGCAGATGTTCGTGAGGCACCTGTTTAATAGGGCAGGAGCAGT
[1735] GGGAGAGAACGTGCCTGACGATCTGTACATCAAGGGCTCCGGCTCTACCGCCAA
[1736] TCTGGCCAGCTCCAACTATTTCCCAACCCCCAGCGGCTCCATGGTGACAAGCGAC
[1737] GCCCAGATCTTTAATAAGCCATACTGGCTGCAGAGGGCCCAGGGCCACAATAAC
[1738] GGCATCTGCTGGGGCAATCAGCTGTTCGTGACCGTGGTGGATACCACACGCTCTA
[1739] CAAACATGAGCCTGTGCGCCGCCATCTCTACCAGCGAGACCACATACAAGAACA
[1740] CAAACTTTAAGGAGTACCTGCGGCACGGCGAGGAGTATGACCTGCAGTTCATCTT
[1741] TCAGCTGTGCAAGATCACCCTGACAGCCGATGTGATGACCTACATCCACTCCATG
[1742] AACAGCACAATCCTGGAGGACTGGAACTTCGGACTGCAGCCACCTCCAGGAGGC ACCCTGGAGGATACATATAGGTTTGTGACCAGCCAGGCCATCGCCTGTCAGAAG
[1743] CACACACCACCTGCACCAAAGGAGGACCCTCTGAAGAAGTACACCTTCTGGGAG
[1744] GTGAACCTGAAGGAGAAGTTTTCCGCCGACCTGGATCAGTTCCCACTGGGACGG
[1745] AAGTTTCTGCTGCAGGCCGGCCTGAAGGCCAAGCCAAAGTTCACCCTGGGCAAG
[1746] AGAAAGGCCACCCCCACCACATCTAGCACATCCACCACAGCCAAGCGGAAGAAG
[1747] AGAAAGCTGTAAGGATCCCTCGAGCTCTCTAGAGTCCGCAAAAATCACCAGTCTC
[1748] TCTCTACAAATCTATCTCTCTCTATTTTTCTCCAGAATAATGTGTGAGTAGTTCCC
[1749] AGATAAGGGAATTAGGGTTCTTATAGGGTTTCGCTCATGTGTTGAGCATATAAGA
[1750] AACCCTTAGTATGTATTTGTATTTGTAAAATACTTCTATCAATAAAATTTCTAATT
[1751] CCTAAAACCAAAATCCAGTGACCGGGCGGCGGGTCGAGAATGATTATTTTATGA
[1752] ATATATTTCATTGTGCAAGTAGATAGAAATTACATATGTTACATAACACACGAAA
[1753] TAAACAAAAAAAGACAATCCAAAAACAAACACCCCAAAAAAAATAATCACTTTA
[1754] GATAAACTCGTATGAGGAGAGGCACGTTCAGTGACTCGACGATTCCCGAGCAAA
[1755] AAAAGTCTCCCCGTCACACATATAGTGGGTGACGCAATTATCTTTAAAGTAATCC
[1756] TTCTGTTGACTTGTCATTGATAACATCCAGTCTTCGTCAGGATTGCAAAGAATTAT
[1757] AGAAGGGATCCCACCTTTTATTTTCTTCTTTTTTCCATATTTAGGGTTGACAGTGA
[1758] AATCAGACTGGCAACCTATTAATTGCTTCCACAATGGGACGAACTTGAAGGGGA
[1759] TGTCGTCGATGATATTATAGGTGGCGTGTTCATCGTAGTTGGTGAAATCGATGGT
[1760] ACCGTTCCAATAGTTGTGTCGTCCGAGACTTCTAGCCCAGGTGGTCTTTCCGGTA
[1761] CGAGTTGGTCCGCAGATGTAGAGGCTGGGGTGTCGGATTCCATTCCTTCCATTGT
[1762] CCTGGTTAAATCGGCCATCCATTCAAGGTCAGATTGAGCTTGTTGGTATGAGACA
[1763] GGATGTATGTAAGTATAAGCGTCTATGCTTACATGGTATAGATGGGTTTCCCTCC
[1764] AGGAGTGTAGATCTTCGTGGCAGCGAAGATCTGATTCTGTGAAGGGCGACACAT
[1765] ACGGTTCAGGTTGTGGAGGGAATAATTTGTTGGCTGAATATTCCAGCCATTGAAG
[1766] TTTTGTTGCCCATTCATGAGGGAATTCTTCCTTGATCATGTCAAGATATTCCTCCT
[1767] TAGACGTTGCAGTCTGGATAATAGTTCTCCATCGTGCGTCAGATTTGCGAGGAGA
[1768] GACCTTATGATCTCGGAAATCTCCTCTGGTTTTAATATCTCCGTCCTTTGATATGT
[1769] AATCAAGGACTTGTTTAGAGTTTCTAGCTGGCTGGATATTAGGGTGATTTCCTTC
[1770] AAAATCGAAAAAAGAAGGATCCCTAATACAAGGTTTTTTATCAAGCTGGAGAAG
[1771] AGCATGATAGTGGGTAGTGCCATCTTGATGAAGCTCAGAAGCAACACCAAGGAA
[1772] GAAAATAAGAAAAGGTGTGAGTTTCTCCCAGAGAAACTGGAATAAATCATCTCT
[1773] TTGAGATGAGCACTTGGGATAGGTAAGGAAAACATATTTAGATTGGAGTCTGAA
[1774] GTTCTTACTAGCAGAAGGCATGTTGTTGTGACTCCGAGGGGTTGCCTCAAACTCT ATCTTATAACCGGCGTGGAGGCATGGAGGCAGGGGTATTTTGGTCATTTTAATAG
[1775] ATAGTGGAAAATGACGTGGAATTTACTTAAAGACGAAGTCTTTGCGACAAGGGG
[1776] GGGCCCACGCCGAATTTAATATTACCGGCGTGGCCCCCCCTTATCGCGAGTGCTT
[1777] TAGCACGAGCGGTCCAGATTTAAAGTAGAAAATTTCCCGCCCACTAGGGTTAAA
[1778] GGTGTTCACACTATACAAGCATATACGATGTGATGGTATTGACTAGAGTTTAAAC
[1779] TATCAGTGTTTGACAGGATATATTGGCGGGTAAACCTAAGAGAAAAGAGCGTTT
[1780] ATTAGAATAATCGGATATTTAAAAGGGCGTGAAAAGGTTTATCCGTTCGTCCATT
[1781] TGTATGTGTACATCACCGACGAGCAAGGCAAGACCGAGCGCCTTTCCGACGCTC
[1782] ACCGGGCTGGTTGCCCTCGCCGCTGGGCTGGCGGCCGTCTATGGCCCTGCAAACG
[1783] CGCCAGAAACGCCGTCGAAGCCGTGTGCGAGACACCGGCCGCCGGCGTTGTGGA
[1784] TACCTCGCGGAAAACTTGGCCCTCACTGACAGATGAGGGGCGGACGTTGACACT
[1785] TGAGGGGCCGACTCACCCGGCGCGGCGTTGACAGATGAGGGGCAGGCTCGATTT
[1786] CGGCCGGCGACGTGGAGCTGGCCAGCCTCGCAAATCGGCGAAAACGCCTGATTT
[1787] TACGCGAGTTTCCCACAGATGATGTGGACAAGCCTGGGGATAAGTGCCCTGCGG
[1788] TATTGACACTTGAGGGGCGCGACTACTGACAGATGAGGGGCGCGATCCTTGACA
[1789] CTTGAGGGGCAGAGTGCTGACAGATGAGGGGCGCACCTATTGACATTTGAGGGG
[1790] CTGTCCACAGGCAGAAAATCCAGCATTTGCAAGGGTTTCCGCCCGTTTTTCGGCC
[1791] ACCGCTAACCTGTCTTTTAACCTGCTTTTAAACCAATATTTATAAACCTTGTTTTT
[1792] AACCAGGGCTGCGCCCTGTGCGCGTGACCGCGCACGCCGAAGGGGGGTGCCCCC
[1793] CCTTCTCGAACCCTCCCGGCCCGCTAACGCGGGCCTCCCATCCCCCCAGGGGCTG
[1794] CGCCCCTCGGCCGCGAACGGCCTCACCCCAAAAATGGCAGCGCTGGCAGTCCTT
[1795] GCCATTGCCGGGATCGGGGCAGTAACGGGATGGGCGATCAGCCCGAAAGCTACC
[1796] CCTATTTGTTTATTTTTCTAAATACATTCAAATATGTATCCGCTCATGAGACAATA
[1797] ACCCTGATAAATGCTTCAATAATATTGAAAAAGGAAGAGTATGAGTATTCAACA
[1798] TTTCCGTGTCGCCCTTATTCCCTTTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCA
[1799] CCCAGAAACGCTGGTGAAAGTAAAAGATGCTGAAGATCAGTTGGGTGCACGAGT
[1800] GGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTGAGAGTTTTCGCCCC
[1801] GAAGAACGTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTAT
[1802] TATCCCGTATTGACGCCGGGCAAGAGCAACTCGGTCGCCGCATACACTATTCTCA
[1803] GAATGACTTGGTTGAGTACTCACCAGTCACAGAAAAGCATCTTACGGATGGCAT
[1804] GACAGTAAGAGAATTATGCAGTGCTGCCATAACCATGAGTGATAACACTGCGGC
[1805] CAACTTACTTCTGACAACGATCGGAGGACCGAAGGAGCTAACCGCTTTTTTGCAC
[1806] AACATGGGGGATCATGTAACTCGCCTTGATCGTTGGGAACCGGAGCTGAATGAA GCCATACCAAACGACGAGCGTGACACCACGATGCCTGTAGCAATGGCAACAACG
[1807] TTGCGCAAACTATTAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAATTAA
[1808] TAGACTGGATGGAGGCGGATAAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTCC
[1809] GGCTGGCTGGTTTATTGCTGATAAATCTGGAGCCGGTGAGCGTGGGTCTCGCGGT
[1810] ATCATTGCAGCACTGGGGCCAGATGGTAAGCCCTCCCGTATCGTAGTTATCTACA
[1811] CGACGGGGAGTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGAGATAG
[1812] GTGCCTCACTGATTAAGCATTGGTAACTGTCAGACCAAGTTTACTCATATATACT
[1813] TTAGATTGATTTAAAACTTCATTTTTAATTTAAAAGGATCTAGGTGAAGATCCTTT
[1814] TTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGTTCCACTGAGCGTC
[1815] AGACCCCGTAGAAAAGATCAAAGGATCTTCTTGAGATCCTTTTTTTCTGCGCGTA
[1816] ATCTGCTGCTTGCAAACAAAAAAACCACCGCTACCAGCGGTGGTTTGTTTGCCGG
[1817] ATCAAGAGCTACCAACTCTTTTTCCGAAGGTAACTGGCTTCAGCAGAGCGCAGAT
[1818] ACCAAATACTGTTCTTCTAGTGTAGCCGTAGTTAGGCCACCACTTCAAGAACTCT
[1819] GTAGCACCGCCTACATACCTCGCTCTGCTAATCCTGTTACCAGTGGCTGCTGCCA
[1820] GTGGCGATAAGTCGTGTCTTACCGGGTTGGACTCAAGACGATAGTTACCGGATAA
[1821] GGCGCAGCGGTCGGGCTGAACGGGGGGTTCGTGCACACAGCCCAGCTTGGAGCG
[1822] AACGACCTACACCGAACTGAGATACCTACAGCGTGAGCTATGAGAAAGCGCCAC
[1823] GCTTCCCGAAGGGAGAAAGGCGGACAGGTATCCGGTAAGCGGCAGGGTCGGAA
[1824] CAGGAGAGCGCACGAGGGAGCTTCCAGGGGGAAACGCCTGGTATCTTTATAGTC
[1825] CTGTCGGGTTTCGCCACCTCTGACTTGAGCGTCGATTTTTGTGATGCTCGTCAGGG
[1826] GGGCGGAGCCTATGGAAAAACGCCAGCAACGCGGCCTTTTTACGGTTCCTGGCCT
[1827] TTTGCTGGCCTTTTGCTCACATGGACTCTAGCTAGAGGATCACAGGCAGCAACGC
[1828] TCTGTCATCGTTACAATCAACATGCTACCCTCCGCGAGATCATCCGTGTTTCAAA
[1829] CCCGGCAGCTTAGTTGCCGTTCTTCCGAATAGCATCGGTAACATGAGCAAAGTCT
[1830] GCCGCCTTACAACGGCTCTCCCGCTGACGCCGTCCCGGACTGATGGGCTGCCTGT
[1831] ATCGAGTGGTGATTTTGTGCCGAGCTGCCGGTCGGGGAGCTGTTGGCTGGCTGGT
[1832] GGCAGGATATATTGTGGTGTAAACAAATTGACGCTTAGACAACTTAATAACACAT
[1833] TGCGGACGTTTTTAATGATCGAATACTAACGTCTCTACCACATT
[1834] 31. SEQ ID NO: 31 - pRIC3 L1:2C7 h4_i (Generation I)
[1835] GAAGAGCGTGACTCCGAGGGGTTGCCTCAAACTCTATCTTATAACCGGCGTGGA
[1836] GGCATGGAGGCAGGGGTATTTTGGTCATTTTAATAGATAGTGGAAAATGACGTG
[1837] GAATTTACTTAAAGACGAAGTCTTTGCGACAAGGGGGGGCCCACGCCGAATTTA ATATTACCGGCGTGGCCCCCCCTTATCGCGAGTGCTTTAGCACGAGCGGTCCAGA
[1838] TTTAAAGTAGAAAATTTCCCGCCCACTAGGGTTAAAGGTGTTCACACTATAAAAG
[1839] CATATACGATGTGATGGTATTTGCTCGACCTGGTCCAAAGACCAGAGGGCTATTG
[1840] AGACTTTTCAACAAAGGGTAATATCGGGAAACCTCCTCGGATTCCATTGCCCAGC
[1841] TATCTGTCACTTCATCGAAAGGACAGTAGAAAAGGAAGATGGCTTCTACAAATG
[1842] CCATCATTGCGATAAAGGAAAGGCTATCGTTCAAGATGCCTCTACCGACAGTGGT
[1843] CCCAAAGATGGACCCCCACCCACGAGGAACATCGTGGAAAAAGAAGACGTTCCA
[1844] ACCACGTCTTCAAAGCAAGTGGATTGATGTGATACATGGTGGAGCACGACACTCT
[1845] CGTCTACTCCAAGAATATCAAAGATACAGTCTCAGAAGACCAGAGGGCTATTGA
[1846] GACTTTTCAACAAAGGGTAATATCGGGAAACCTCCTCGGATTCCATTGCCCAGCT
[1847] ATCTGTCACTTCATCGAAAGGACAGTAGAAAAGGAAGATGGCTTCTACAAATGC
[1848] CATCATTGCGATAAAGGAAAGGCTATCGTTCAAGATGCCTCTACCGACAGTGGTC
[1849] CCAAAGATGGACCCCCACCCACGAGGAACATCGTGGAAAAAGAAGACGTTCCAA
[1850] CCACGTCTTCAAAGCAAGTGGATTGATGTGATATCTCCACTGACGTAAGGGATGA
[1851] CGCACAATCCCACTATCCTTCGCAAGACCCTTCCTCTATATAAGGAAGTTCATTTC
[1852] ATTTGGAGAGGACACGCTGAGTTCACAACACAAATCAGATTTATAGAGAGATTT
[1853] ATAAAAAAAAAAAAACATGAGTCTGTGGCTGCCATCTGAGGCAACCGTGTACCT
[1854] GCCACCTGTGCCTGTGAGCAAGGTGGTGTCCACCGATGAGTATGTGGCCCGGAC
[1855] AAATATCTACTATCACGCAGGCACATCCAGACTGCTGGCAGTGGGCCACCCTTAC
[1856] TTCCCAATCAAGAAGCCTAACAATAACAAGATCCTGGTGCCAAAGGTGTCCGGC
[1857] CTGCAGTATAGGGTGTTCCGCATCCACCTGCCAGACCCCAATAAGTTCGGCTTTC
[1858] CAGACACCTCTTTTTACAACCCCGATACACAGAGGCTGGTGTGGGCATGCGTGGG
[1859] AGTGGAAGTGGGAAGGGGCCAGCCACTGGGCGTGGGCATCTCCGGCCACCCCCT
[1860] GCTGAATAAGCTGGACGATACCGAGAACGCCTCTGCCTACGCAGCAAATGCAGG
[1861] AGTGGACAACAGGGAGTGTATCAGCATGGATTATAAGCAGACCCAGCTGTGCCT
[1862] GATCGGCTGTAAGCCACCAATCGGAGAGCACTGGGGCAAGGGATCTCCATGCAC
[1863] AAATGTGGCCGTGAACCCTGGCGATTGTCCTCCACTGGAGCTGATCAATACCGTG
[1864] ATCCAGGACGGCGATATGGTGGACACAGGCTTCGGCGCCATGGACTTCACCACC
[1865] CTGCAGGCCAACAAGTCTGAGGTGCCTCTGGACATCTGCACCAGCATCTGTAAGT
[1866] ACCCTGATTATATCAAGATGGTGAGCGAGCCATACGGCGACTCCCTGTTCTTTTA
[1867] TCTGCGGAGAGAGCAGATGTTCGTGAGGCACCTGTTTAATAGGGCAGGAGCAGT
[1868] GGGAGAGAACGTGCCTGACGATCTGTACATCAAGGGCTCCGGCTCTACCGCCAA
[1869] TCTGGCCAGCTCCAACTATTTCCCTACCCCAAGCGGCTCCATGGTGACAAGCGAT GCCCAGATCTTTAACAAGCCATACTGGCTGCAGAGGGCCCAGGGCCACAATAAC
[1870] GGCATCTGCTGGGGCAATCAGCTGTTCGTGACCGTGGTGGACACCACACGCTCTA
[1871] CAAACATGAGCCTGTGCGCCGCCATCTCTACCAGCGAGACCACATACAAGAACA
[1872] CAAACTTTAAGGAGTACCTGCGGCACGGCGAGGAGTATGACCTGCAGTTCATCTT
[1873] TCAGCTGTGCAAGATCACCCTGACAGCCGATGTGATGACCTACATCCACTCCATG
[1874] AACAGCACAATCCTGGAGGACTGGAACTTCGGCCTGCAGCCACCTCCAGGAGGC
[1875] ACCCTGTGCGGACCAATCCCTGTGCTGGACGAGAATGGACTGTTCGCACCAGGA
[1876] CCATGCGAGGATACCTATAGGTTTGTGACAAGCCAGGCCATCGCATGTCAGAAG
[1877] CACACCCCACCTGCACCAAAGGAGGACCCTCTGAAGAAGTACACATTCTGGGAG
[1878] GTGAACCTGAAGGAGAAGTTTTCCGCCGACCTGGATCAGTTCCCACTGGGACGG
[1879] AAGTTTCTGCTGCAGGCCGGCCTGAAGGCCAAGCCAAAGTTTACCCTGGGCAAG
[1880] AGAAAGGCCACCCCCACCACATCTAGCACAAGCACCACAGCCAAGCGGAAGAA
[1881] GAGAAAGCTGTAAGGATCCCTCGAGCTCTCTAGAGTCCGCAAAAATCACCAGTC
[1882] TCTCTCTACAAATCTATCTCTCTCTATTTTTCTCCAGAATAATGTGTGAGTAGTTC
[1883] CCAGATAAGGGAATTAGGGTTCTTATAGGGTTTCGCTCATGTGTTGAGCATATAA
[1884] GAAACCCTTAGTATGTATTTGTATTTGTAAAATACTTCTATCAATAAAATTTCTAA
[1885] TTCCTAAAACCAAAATCCAGTGACCGGGCGGCGGGTCGAGAATGATTATTTTATG
[1886] AATATATTTCATTGTGCAAGTAGATAGAAATTACATATGTTACATAACACACGAA
[1887] ATAAACAAAAAAAGACAATCCAAAAACAAACACCCCAAAAAAAATAATCACTTT
[1888] AGATAAACTCGTATGAGGAGAGGCACGTTCAGTGACTCGACGATTCCCGAGCAA
[1889] AAAAAGTCTCCCCGTCACACATATAGTGGGTGACGCAATTATCTTTAAAGTAATC
[1890] CTTCTGTTGACTTGTCATTGATAACATCCAGTCTTCGTCAGGATTGCAAAGAATTA
[1891] TAGAAGGGATCCCACCTTTTATTTTCTTCTTTTTTCCATATTTAGGGTTGACAGTG
[1892] AAATCAGACTGGCAACCTATTAATTGCTTCCACAATGGGACGAACTTGAAGGGG
[1893] ATGTCGTCGATGATATTATAGGTGGCGTGTTCATCGTAGTTGGTGAAATCGATGG
[1894] TACCGTTCCAATAGTTGTGTCGTCCGAGACTTCTAGCCCAGGTGGTCTTTCCGGTA
[1895] CGAGTTGGTCCGCAGATGTAGAGGCTGGGGTGTCGGATTCCATTCCTTCCATTGT
[1896] CCTGGTTAAATCGGCCATCCATTCAAGGTCAGATTGAGCTTGTTGGTATGAGACA
[1897] GGATGTATGTAAGTATAAGCGTCTATGCTTACATGGTATAGATGGGTTTCCCTCC
[1898] AGGAGTGTAGATCTTCGTGGCAGCGAAGATCTGATTCTGTGAAGGGCGACACAT
[1899] ACGGTTCAGGTTGTGGAGGGAATAATTTGTTGGCTGAATATTCCAGCCATTGAAG
[1900] TTTTGTTGCCCATTCATGAGGGAATTCTTCCTTGATCATGTCAAGATATTCCTCCT
[1901] TAGACGTTGCAGTCTGGATAATAGTTCTCCATCGTGCGTCAGATTTGCGAGGAGA GACCTTATGATCTCGGAAATCTCCTCTGGTTTTAATATCTCCGTCCTTTGATATGT
[1902] AATCAAGGACTTGTTTAGAGTTTCTAGCTGGCTGGATATTAGGGTGATTTCCTTC
[1903] AAAATCGAAAAAAGAAGGATCCCTAATACAAGGTTTTTTATCAAGCTGGAGAAG
[1904] AGCATGATAGTGGGTAGTGCCATCTTGATGAAGCTCAGAAGCAACACCAAGGAA
[1905] GAAAATAAGAAAAGGTGTGAGTTTCTCCCAGAGAAACTGGAATAAATCATCTCT
[1906] TTGAGATGAGCACTTGGGATAGGTAAGGAAAACATATTTAGATTGGAGTCTGAA
[1907] GTTCTTACTAGCAGAAGGCATGTTGTTGTGACTCCGAGGGGTTGCCTCAAACTCT
[1908] ATCTTATAACCGGCGTGGAGGCATGGAGGCAGGGGTATTTTGGTCATTTTAATAG
[1909] ATAGTGGAAAATGACGTGGAATTTACTTAAAGACGAAGTCTTTGCGACAAGGGG
[1910] GGGCCCACGCCGAATTTAATATTACCGGCGTGGCCCCCCCTTATCGCGAGTGCTT
[1911] TAGCACGAGCGGTCCAGATTTAAAGTAGAAAATTTCCCGCCCACTAGGGTTAAA
[1912] GGTGTTCACACTATACAAGCATATACGATGTGATGGTATTGACTAGAGTTTAAAC
[1913] TATCAGTGTTTGACAGGATATATTGGCGGGTAAACCTAAGAGAAAAGAGCGTTT
[1914] ATTAGAATAATCGGATATTTAAAAGGGCGTGAAAAGGTTTATCCGTTCGTCCATT
[1915] TGTATGTGTACATCACCGACGAGCAAGGCAAGACCGAGCGCCTTTCCGACGCTC
[1916] ACCGGGCTGGTTGCCCTCGCCGCTGGGCTGGCGGCCGTCTATGGCCCTGCAAACG
[1917] CGCCAGAAACGCCGTCGAAGCCGTGTGCGAGACACCGGCCGCCGGCGTTGTGGA
[1918] TACCTCGCGGAAAACTTGGCCCTCACTGACAGATGAGGGGCGGACGTTGACACT
[1919] TGAGGGGCCGACTCACCCGGCGCGGCGTTGACAGATGAGGGGCAGGCTCGATTT
[1920] CGGCCGGCGACGTGGAGCTGGCCAGCCTCGCAAATCGGCGAAAACGCCTGATTT
[1921] TACGCGAGTTTCCCACAGATGATGTGGACAAGCCTGGGGATAAGTGCCCTGCGG
[1922] TATTGACACTTGAGGGGCGCGACTACTGACAGATGAGGGGCGCGATCCTTGACA
[1923] CTTGAGGGGCAGAGTGCTGACAGATGAGGGGCGCACCTATTGACATTTGAGGGG
[1924] CTGTCCACAGGCAGAAAATCCAGCATTTGCAAGGGTTTCCGCCCGTTTTTCGGCC
[1925] ACCGCTAACCTGTCTTTTAACCTGCTTTTAAACCAATATTTATAAACCTTGTTTTT
[1926] AACCAGGGCTGCGCCCTGTGCGCGTGACCGCGCACGCCGAAGGGGGGTGCCCCC
[1927] CCTTCTCGAACCCTCCCGGCCCGCTAACGCGGGCCTCCCATCCCCCCAGGGGCTG
[1928] CGCCCCTCGGCCGCGAACGGCCTCACCCCAAAAATGGCAGCGCTGGCAGTCCTT
[1929] GCCATTGCCGGGATCGGGGCAGTAACGGGATGGGCGATCAGCCCGAAAGCTACC
[1930] CCTATTTGTTTATTTTTCTAAATACATTCAAATATGTATCCGCTCATGAGACAATA
[1931] ACCCTGATAAATGCTTCAATAATATTGAAAAAGGAAGAGTATGAGTATTCAACA
[1932] TTTCCGTGTCGCCCTTATTCCCTTTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCA
[1933] CCCAGAAACGCTGGTGAAAGTAAAAGATGCTGAAGATCAGTTGGGTGCACGAGT GGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTGAGAGTTTTCGCCCC
[1934] GAAGAACGTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTAT
[1935] TATCCCGTATTGACGCCGGGCAAGAGCAACTCGGTCGCCGCATACACTATTCTCA
[1936] GAATGACTTGGTTGAGTACTCACCAGTCACAGAAAAGCATCTTACGGATGGCAT
[1937] GACAGTAAGAGAATTATGCAGTGCTGCCATAACCATGAGTGATAACACTGCGGC
[1938] CAACTTACTTCTGACAACGATCGGAGGACCGAAGGAGCTAACCGCTTTTTTGCAC
[1939] AACATGGGGGATCATGTAACTCGCCTTGATCGTTGGGAACCGGAGCTGAATGAA
[1940] GCCATACCAAACGACGAGCGTGACACCACGATGCCTGTAGCAATGGCAACAACG
[1941] TTGCGCAAACTATTAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAATTAA
[1942] TAGACTGGATGGAGGCGGATAAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTCC
[1943] GGCTGGCTGGTTTATTGCTGATAAATCTGGAGCCGGTGAGCGTGGGTCTCGCGGT
[1944] ATCATTGCAGCACTGGGGCCAGATGGTAAGCCCTCCCGTATCGTAGTTATCTACA
[1945] CGACGGGGAGTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGAGATAG
[1946] GTGCCTCACTGATTAAGCATTGGTAACTGTCAGACCAAGTTTACTCATATATACT
[1947] TTAGATTGATTTAAAACTTCATTTTTAATTTAAAAGGATCTAGGTGAAGATCCTTT
[1948] TTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGTTCCACTGAGCGTC
[1949] AGACCCCGTAGAAAAGATCAAAGGATCTTCTTGAGATCCTTTTTTTCTGCGCGTA
[1950] ATCTGCTGCTTGCAAACAAAAAAACCACCGCTACCAGCGGTGGTTTGTTTGCCGG
[1951] ATCAAGAGCTACCAACTCTTTTTCCGAAGGTAACTGGCTTCAGCAGAGCGCAGAT
[1952] ACCAAATACTGTTCTTCTAGTGTAGCCGTAGTTAGGCCACCACTTCAAGAACTCT
[1953] GTAGCACCGCCTACATACCTCGCTCTGCTAATCCTGTTACCAGTGGCTGCTGCCA
[1954] GTGGCGATAAGTCGTGTCTTACCGGGTTGGACTCAAGACGATAGTTACCGGATAA
[1955] GGCGCAGCGGTCGGGCTGAACGGGGGGTTCGTGCACACAGCCCAGCTTGGAGCG
[1956] AACGACCTACACCGAACTGAGATACCTACAGCGTGAGCTATGAGAAAGCGCCAC
[1957] GCTTCCCGAAGGGAGAAAGGCGGACAGGTATCCGGTAAGCGGCAGGGTCGGAA
[1958] CAGGAGAGCGCACGAGGGAGCTTCCAGGGGGAAACGCCTGGTATCTTTATAGTC
[1959] CTGTCGGGTTTCGCCACCTCTGACTTGAGCGTCGATTTTTGTGATGCTCGTCAGGG
[1960] GGGCGGAGCCTATGGAAAAACGCCAGCAACGCGGCCTTTTTACGGTTCCTGGCCT
[1961] TTTGCTGGCCTTTTGCTCACATGGACTCTAGCTAGAGGATCACAGGCAGCAACGC
[1962] TCTGTCATCGTTACAATCAACATGCTACCCTCCGCGAGATCATCCGTGTTTCAAA
[1963] CCCGGCAGCTTAGTTGCCGTTCTTCCGAATAGCATCGGTAACATGAGCAAAGTCT
[1964] GCCGCCTTACAACGGCTCTCCCGCTGACGCCGTCCCGGACTGATGGGCTGCCTGT
[1965] ATCGAGTGGTGATTTTGTGCCGAGCTGCCGGTCGGGGAGCTGTTGGCTGGCTGGT GGCAGGATATATTGTGGTGTAAACAAATTGACGCTTAGACAACTTAATAACACAT
[1966] TGCGGACGTTTTTAATGATCGAATACTAACGTCTCTACCACATT
[1967] 32. SEQ ID NO: 32 - pRIC3 L1:2C7 h4_s (Generation I)
[1968] GAAGAGCGTGACTCCGAGGGGTTGCCTCAAACTCTATCTTATAACCGGCGTGGA
[1969] GGCATGGAGGCAGGGGTATTTTGGTCATTTTAATAGATAGTGGAAAATGACGTG
[1970] GAATTTACTTAAAGACGAAGTCTTTGCGACAAGGGGGGGCCCACGCCGAATTTA
[1971] ATATTACCGGCGTGGCCCCCCCTTATCGCGAGTGCTTTAGCACGAGCGGTCCAGA
[1972] TTTAAAGTAGAAAATTTCCCGCCCACTAGGGTTAAAGGTGTTCACACTATAAAAG
[1973] CATATACGATGTGATGGTATTTGCTCGACCTGGTCCAAAGACCAGAGGGCTATTG
[1974] AGACTTTTCAACAAAGGGTAATATCGGGAAACCTCCTCGGATTCCATTGCCCAGC
[1975] TATCTGTCACTTCATCGAAAGGACAGTAGAAAAGGAAGATGGCTTCTACAAATG
[1976] CCATCATTGCGATAAAGGAAAGGCTATCGTTCAAGATGCCTCTACCGACAGTGGT
[1977] CCCAAAGATGGACCCCCACCCACGAGGAACATCGTGGAAAAAGAAGACGTTCCA
[1978] ACCACGTCTTCAAAGCAAGTGGATTGATGTGATACATGGTGGAGCACGACACTCT
[1979] CGTCTACTCCAAGAATATCAAAGATACAGTCTCAGAAGACCAGAGGGCTATTGA
[1980] GACTTTTCAACAAAGGGTAATATCGGGAAACCTCCTCGGATTCCATTGCCCAGCT
[1981] ATCTGTCACTTCATCGAAAGGACAGTAGAAAAGGAAGATGGCTTCTACAAATGC
[1982] CATCATTGCGATAAAGGAAAGGCTATCGTTCAAGATGCCTCTACCGACAGTGGTC
[1983] CCAAAGATGGACCCCCACCCACGAGGAACATCGTGGAAAAAGAAGACGTTCCAA
[1984] CCACGTCTTCAAAGCAAGTGGATTGATGTGATATCTCCACTGACGTAAGGGATGA
[1985] CGCACAATCCCACTATCCTTCGCAAGACCCTTCCTCTATATAAGGAAGTTCATTTC
[1986] ATTTGGAGAGGACACGCTGAGTTCACAACACAAATCAGATTTATAGAGAGATTT
[1987] ATAAAAAAAAAAAAACATGAGTCTGTGGCTGCCATCTGAGGCAACCGTGTACCT
[1988] GCCACCTGTGCCTGTGAGCAAGGTGGTGTCCACCGATGAGTATGTGGCCCGGAC
[1989] AAATATCTACTATCACGCAGGCACATCCAGACTGCTGGCAGTGGGCCACCCTTAC
[1990] TTCCCAATCAAGAAGCCTAACAATAACAAGATCCTGGTGCCAAAGGTGTCCGGC
[1991] CTGCAGTATAGGGTGTTCCGCATCCACCTGCCAGACCCCAATAAGTTCGGCTTTC
[1992] CAGACACCTCTTTTTACAACCCCGATACACAGAGGCTGGTGTGGGCATGCGTGGG
[1993] AGTGGAAGTGGGAAGGGGCCAGCCACTGGGCGTGGGCATCTCCGGCCACCCCCT
[1994] GCTGAATAAGCTGGACGATACCGAGAACGCCTCTGCCTACGCAGCAAATGCAGG
[1995] AGTGGACAACAGGGAGTGTATCAGCATGGATTATAAGCAGACCCAGCTGTGCCT
[1996] GATCGGCTGTAAGCCACCAATCGGAGAGCACTGGGGCAAGGGATCTCCATGCAC AAATGTGGCCGTGAACCCTGGCGATTGTCCTCCACTGGAGCTGATCAATACCGTG
[1997] ATCCAGGACGGCGATATGGTGGACACAGGCTTCGGCGCCATGGACTTCACCACC
[1998] CTGCAGGCCAACAAGTCTGAGGTGCCTCTGGACATCTGCACCAGCATCTGTAAGT
[1999] ACCCTGATTATATCAAGATGGTGAGCGAGCCATACGGCGACTCCCTGTTCTTTTA
[2000] TCTGCGGAGAGAGCAGATGTTCGTGAGGCACCTGTTTAATAGGGCAGGAGCAGT
[2001] GGGAGAGAACGTGCCTGACGATCTGTACATCAAGGGCTCCGGCTCTACCGCCAA
[2002] TCTGGCCAGCTCCAACTATTTCCCTACCCCAAGCGGCTCCATGGTGACAAGCGAT
[2003] GCCCAGATCTTTAACAAGCCATATTGGCTGCAGAGGGCCCAGGGCCACAATAAC
[2004] GGCATCTGCTGGGGCAATCAGCTGTTCGTGACCGTGGTGGACACCACACGCTCTA
[2005] CAAACATGAGCCTGTGCGCCGCCATCTCTACCAGCGAGACCACATACAAGAACA
[2006] CAAACTTTAAGGAGTACCTGAGGCACGGCGAGGAGTATGACCTGCAGTTCATCTT
[2007] TCAGCTGTGCAAGATCACCCTGACAGCCGATGTGATGACCTACATCCACTCCATG
[2008] AACAGCACAATCCTGGAGGACTGGAACTTCGGCCTGCAGCCACCTCCAGGAGGA
[2009] ACCTGCGGACCCATCCCTGTGCTGGATGAGAATGGACTGTTTGCACCAGGACCAT
[2010] GTACCCCACCTGCACCAAAGGAGGACCCTCTGAAGAAGTACACATTCTGGGAGG
[2011] TGAACCTGAAGGAGAAGTTTAGCGCCGACCTGGATCAGTTCCCACTGGGACGGA
[2012] AGTTTCTGCTGCAGGCCGGCCTGAAGGCCAAGCCAAAGTTCACCCTGGGCAAGA
[2013] GAAAGGCCACCCCCACCACATCTAGCACATCCACCACAGCCAAGCGGAAGAAGA
[2014] GAAAGCTGTAAGGATCCCTCGAGCTCTCTAGAGTCCGCAAAAATCACCAGTCTCT
[2015] CTCTACAAATCTATCTCTCTCTATTTTTCTCCAGAATAATGTGTGAGTAGTTCCCA
[2016] GATAAGGGAATTAGGGTTCTTATAGGGTTTCGCTCATGTGTTGAGCATATAAGAA
[2017] ACCCTTAGTATGTATTTGTATTTGTAAAATACTTCTATCAATAAAATTTCTAATTC
[2018] CTAAAACCAAAATCCAGTGACCGGGCGGCGGGTCGAGAATGATTATTTTATGAA
[2019] TATATTTCATTGTGCAAGTAGATAGAAATTACATATGTTACATAACACACGAAAT
[2020] AAACAAAAAAAGACAATCCAAAAACAAACACCCCAAAAAAAATAATCACTTTA
[2021] GATAAACTCGTATGAGGAGAGGCACGTTCAGTGACTCGACGATTCCCGAGCAAA
[2022] AAAAGTCTCCCCGTCACACATATAGTGGGTGACGCAATTATCTTTAAAGTAATCC
[2023] TTCTGTTGACTTGTCATTGATAACATCCAGTCTTCGTCAGGATTGCAAAGAATTAT
[2024] AGAAGGGATCCCACCTTTTATTTTCTTCTTTTTTCCATATTTAGGGTTGACAGTGA
[2025] AATCAGACTGGCAACCTATTAATTGCTTCCACAATGGGACGAACTTGAAGGGGA
[2026] TGTCGTCGATGATATTATAGGTGGCGTGTTCATCGTAGTTGGTGAAATCGATGGT
[2027] ACCGTTCCAATAGTTGTGTCGTCCGAGACTTCTAGCCCAGGTGGTCTTTCCGGTA
[2028] CGAGTTGGTCCGCAGATGTAGAGGCTGGGGTGTCGGATTCCATTCCTTCCATTGT CCTGGTTAAATCGGCCATCCATTCAAGGTCAGATTGAGCTTGTTGGTATGAGACA
[2029] GGATGTATGTAAGTATAAGCGTCTATGCTTACATGGTATAGATGGGTTTCCCTCC
[2030] AGGAGTGTAGATCTTCGTGGCAGCGAAGATCTGATTCTGTGAAGGGCGACACAT
[2031] ACGGTTCAGGTTGTGGAGGGAATAATTTGTTGGCTGAATATTCCAGCCATTGAAG
[2032] TTTTGTTGCCCATTCATGAGGGAATTCTTCCTTGATCATGTCAAGATATTCCTCCT
[2033] TAGACGTTGCAGTCTGGATAATAGTTCTCCATCGTGCGTCAGATTTGCGAGGAGA
[2034] GACCTTATGATCTCGGAAATCTCCTCTGGTTTTAATATCTCCGTCCTTTGATATGT
[2035] AATCAAGGACTTGTTTAGAGTTTCTAGCTGGCTGGATATTAGGGTGATTTCCTTC
[2036] AAAATCGAAAAAAGAAGGATCCCTAATACAAGGTTTTTTATCAAGCTGGAGAAG
[2037] AGCATGATAGTGGGTAGTGCCATCTTGATGAAGCTCAGAAGCAACACCAAGGAA
[2038] GAAAATAAGAAAAGGTGTGAGTTTCTCCCAGAGAAACTGGAATAAATCATCTCT
[2039] TTGAGATGAGCACTTGGGATAGGTAAGGAAAACATATTTAGATTGGAGTCTGAA
[2040] GTTCTTACTAGCAGAAGGCATGTTGTTGTGACTCCGAGGGGTTGCCTCAAACTCT
[2041] ATCTTATAACCGGCGTGGAGGCATGGAGGCAGGGGTATTTTGGTCATTTTAATAG
[2042] ATAGTGGAAAATGACGTGGAATTTACTTAAAGACGAAGTCTTTGCGACAAGGGG
[2043] GGGCCCACGCCGAATTTAATATTACCGGCGTGGCCCCCCCTTATCGCGAGTGCTT
[2044] TAGCACGAGCGGTCCAGATTTAAAGTAGAAAATTTCCCGCCCACTAGGGTTAAA
[2045] GGTGTTCACACTATACAAGCATATACGATGTGATGGTATTGACTAGAGTTTAAAC
[2046] TATCAGTGTTTGACAGGATATATTGGCGGGTAAACCTAAGAGAAAAGAGCGTTT
[2047] ATTAGAATAATCGGATATTTAAAAGGGCGTGAAAAGGTTTATCCGTTCGTCCATT
[2048] TGTATGTGTACATCACCGACGAGCAAGGCAAGACCGAGCGCCTTTCCGACGCTC
[2049] ACCGGGCTGGTTGCCCTCGCCGCTGGGCTGGCGGCCGTCTATGGCCCTGCAAACG
[2050] CGCCAGAAACGCCGTCGAAGCCGTGTGCGAGACACCGGCCGCCGGCGTTGTGGA
[2051] TACCTCGCGGAAAACTTGGCCCTCACTGACAGATGAGGGGCGGACGTTGACACT
[2052] TGAGGGGCCGACTCACCCGGCGCGGCGTTGACAGATGAGGGGCAGGCTCGATTT
[2053] CGGCCGGCGACGTGGAGCTGGCCAGCCTCGCAAATCGGCGAAAACGCCTGATTT
[2054] TACGCGAGTTTCCCACAGATGATGTGGACAAGCCTGGGGATAAGTGCCCTGCGG
[2055] TATTGACACTTGAGGGGCGCGACTACTGACAGATGAGGGGCGCGATCCTTGACA
[2056] CTTGAGGGGCAGAGTGCTGACAGATGAGGGGCGCACCTATTGACATTTGAGGGG
[2057] CTGTCCACAGGCAGAAAATCCAGCATTTGCAAGGGTTTCCGCCCGTTTTTCGGCC
[2058] ACCGCTAACCTGTCTTTTAACCTGCTTTTAAACCAATATTTATAAACCTTGTTTTT
[2059] AACCAGGGCTGCGCCCTGTGCGCGTGACCGCGCACGCCGAAGGGGGGTGCCCCC
[2060] CCTTCTCGAACCCTCCCGGCCCGCTAACGCGGGCCTCCCATCCCCCCAGGGGCTG CGCCCCTCGGCCGCGAACGGCCTCACCCCAAAAATGGCAGCGCTGGCAGTCCTT
[2061] GCCATTGCCGGGATCGGGGCAGTAACGGGATGGGCGATCAGCCCGAAAGCTACC
[2062] CCTATTTGTTTATTTTTCTAAATACATTCAAATATGTATCCGCTCATGAGACAATA
[2063] ACCCTGATAAATGCTTCAATAATATTGAAAAAGGAAGAGTATGAGTATTCAACA
[2064] TTTCCGTGTCGCCCTTATTCCCTTTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCA
[2065] CCCAGAAACGCTGGTGAAAGTAAAAGATGCTGAAGATCAGTTGGGTGCACGAGT
[2066] GGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTGAGAGTTTTCGCCCC
[2067] GAAGAACGTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTAT
[2068] TATCCCGTATTGACGCCGGGCAAGAGCAACTCGGTCGCCGCATACACTATTCTCA
[2069] GAATGACTTGGTTGAGTACTCACCAGTCACAGAAAAGCATCTTACGGATGGCAT
[2070] GACAGTAAGAGAATTATGCAGTGCTGCCATAACCATGAGTGATAACACTGCGGC
[2071] CAACTTACTTCTGACAACGATCGGAGGACCGAAGGAGCTAACCGCTTTTTTGCAC
[2072] AACATGGGGGATCATGTAACTCGCCTTGATCGTTGGGAACCGGAGCTGAATGAA
[2073] GCCATACCAAACGACGAGCGTGACACCACGATGCCTGTAGCAATGGCAACAACG
[2074] TTGCGCAAACTATTAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAATTAA
[2075] TAGACTGGATGGAGGCGGATAAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTCC
[2076] GGCTGGCTGGTTTATTGCTGATAAATCTGGAGCCGGTGAGCGTGGGTCTCGCGGT
[2077] ATCATTGCAGCACTGGGGCCAGATGGTAAGCCCTCCCGTATCGTAGTTATCTACA
[2078] CGACGGGGAGTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGAGATAG
[2079] GTGCCTCACTGATTAAGCATTGGTAACTGTCAGACCAAGTTTACTCATATATACT
[2080] TTAGATTGATTTAAAACTTCATTTTTAATTTAAAAGGATCTAGGTGAAGATCCTTT
[2081] TTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGTTCCACTGAGCGTC
[2082] AGACCCCGTAGAAAAGATCAAAGGATCTTCTTGAGATCCTTTTTTTCTGCGCGTA
[2083] ATCTGCTGCTTGCAAACAAAAAAACCACCGCTACCAGCGGTGGTTTGTTTGCCGG
[2084] ATCAAGAGCTACCAACTCTTTTTCCGAAGGTAACTGGCTTCAGCAGAGCGCAGAT
[2085] ACCAAATACTGTTCTTCTAGTGTAGCCGTAGTTAGGCCACCACTTCAAGAACTCT
[2086] GTAGCACCGCCTACATACCTCGCTCTGCTAATCCTGTTACCAGTGGCTGCTGCCA
[2087] GTGGCGATAAGTCGTGTCTTACCGGGTTGGACTCAAGACGATAGTTACCGGATAA
[2088] GGCGCAGCGGTCGGGCTGAACGGGGGGTTCGTGCACACAGCCCAGCTTGGAGCG
[2089] AACGACCTACACCGAACTGAGATACCTACAGCGTGAGCTATGAGAAAGCGCCAC
[2090] GCTTCCCGAAGGGAGAAAGGCGGACAGGTATCCGGTAAGCGGCAGGGTCGGAA
[2091] CAGGAGAGCGCACGAGGGAGCTTCCAGGGGGAAACGCCTGGTATCTTTATAGTC
[2092] CTGTCGGGTTTCGCCACCTCTGACTTGAGCGTCGATTTTTGTGATGCTCGTCAGGG GGGCGGAGCCTATGGAAAAACGCCAGCAACGCGGCCTTTTTACGGTTCCTGGCCT
[2093] TTTGCTGGCCTTTTGCTCACATGGACTCTAGCTAGAGGATCACAGGCAGCAACGC
[2094] TCTGTCATCGTTACAATCAACATGCTACCCTCCGCGAGATCATCCGTGTTTCAAA
[2095] CCCGGCAGCTTAGTTGCCGTTCTTCCGAATAGCATCGGTAACATGAGCAAAGTCT
[2096] GCCGCCTTACAACGGCTCTCCCGCTGACGCCGTCCCGGACTGATGGGCTGCCTGT
[2097] ATCGAGTGGTGATTTTGTGCCGAGCTGCCGGTCGGGGAGCTGTTGGCTGGCTGGT
[2098] GGCAGGATATATTGTGGTGTAAACAAATTGACGCTTAGACAACTTAATAACACAT
[2099] TGCGGACGTTTTTAATGATCGAATACTAACGTCTCTACCACATT
[2100] 33. SEQ ID NO: 33 - pTRAkc-rbcsl-cTP L1:2C7 DE_i (Generation II)
[2101] AATTCCGCCCCTAGAAATATTTGCGACTCTTCTGGCATGTAATATTTCGTTAAATA
[2102] TGAAGTGCTCCATTTTTATTAACTTTAAATAATTGGTTGTACGATCACTTTCTTAT
[2103] CAAGCGTTACTAAAATGCGTCAATCTCTTTGTTCTTCCATATTCATATGTCAAAAT
[2104] CTATCAAAATTCTTATATATCTTTTTCGAATTTGAAGTGAAATTTCGATAATTTAA
[2105] AATTAAATAGAACATATCATTATTTAGGTGTCATATTGATTTTTATACTTAATTAC
[2106] TAAATTTGGTTAACTTTGAAAGTGTACATCAACGAAAAATTAGTCAAACGACTAA
[2107] AATAAATAAATATCATGTGTTATTAAGAAAATTCTCCTATAAGAATATTTTAATA
[2108] GATCATATGTTTGTAAAAAAAATTAATTTTTACTAACACATATATTTACTTATCAA
[2109] AAATTTGACAAAGTAAGATTAAAATAATATTCATCTAACAAAAAAAAACCAGAA
[2110] AATGCTGAAAACCCGGCAAAACCGAACCAATCCAAACCGATATAGTTGGTTTGG
[2111] TTTGATTTTGATATAAACCGAACCAACTCGGTCCATTTGCACCCCTAATCATAAT
[2112] AGCTTTAATATTTCAAGATATTATTAAGTTAACGTTGTCAATATCCTGGAAATTTT
[2113] GCAAAATGAATCAAGCCTATATGGCTGTAATATGAATTTAAAAGCAGCTCGATGT
[2114] GGTGGTAATATGTAATTTACTTGATTCTAAAAAAATATCCCAAGTATTAATAATT
[2115] TCTGCTAGGAAGAAGGTTAGCTACGATTTACAGCAAAGCCAGAATACAAAGAAC
[2116] CATAAAGTGATTGAAGCTCGAAATATACGAAGGAACAAATATTTTTAAAAAAAT
[2117] ACGCAATGACTTGGAACAAAAGAAAGTGATATATTTTTTGTTCTTAAACAAGCAT
[2118] CCCCTCTAAAGAATGGCAGTTTTCCTTTGCATGTAACTATTATGCTCCCTTCGTTA
[2119] CAAAAATTTTGGACTACTATTGGGCGCGGGGCGCGCCCGGTCCAAAGACCAGAG
[2120] GGCTATTGAGACTTTTCAACAAAGGGTAATATCGGGAAACCTCCTCGGATTCCAT
[2121] TGCCCAGCTATCTGTCACTTCATCGAAAGGACAGTAGAAAAGGAAGATGGCTTCT
[2122] ACAAATGCCATCATTGCGATAAAGGAAAGGCTATCGTTCAAGATGCCTCTACCG
[2123] ACAGTGGTCCCAAAGATGGACCCCCACCCACGAGGAACATCGTGGAAAAAGAAG ACGTTCCAACCACGTCTTCAAAGCAAGTGGATTGATGTGATACATGGTGGAGCAC
[2124] GACACTCTCGTCTACTCCAAGAATATCAAAGATACAGTCTCAGAAGACCAGAGG
[2125] GCTATTGAGACTTTTCAACAAAGGGTAATATCGGGAAACCTCCTCGGATTCCATT
[2126] GCCCAGCTATCTGTCACTTCATCGAAAGGACAGTAGAAAAGGAAGATGGCTTCT
[2127] ACAAATGCCATCATTGCGATAAAGGAAAGGCTATCGTTCAAGATGCCTCTACCG
[2128] ACAGTGGTCCCAAAGATGGACCCCCACCCACGAGGAACATCGTGGAAAAAGAAG
[2129] ACGTTCCAACCACGTCTTCAAAGCAAGTGGATTGATGTGATATCTCCACTGACGT
[2130] AAGGGATGACGCACAATCCCACTATCCTTCGCAAGACCCTTCCTCTATATAAGGA
[2131] AGTTCATTTCATTTGGAGAGGACACGCTGAATTCACAACACAAATCAGATTTATA
[2132] GAGAGATTTATAAAAAAAAAAAAAACAATGGCTTCCTCTGTTATTTCCTCTGCAG
[2133] CTGTTGCTACACGCACCAATGTTACACAAGCTGGCAGCATGATTGCACCTTTCAC
[2134] TGGTCTCAAATCTGCTGCTACTTTCCCTGTTTCAAGGAAGCAAAACCTTGACATC
[2135] ACTTCCATTGCTAGCAATGGTGGACGCGTTAGGTTCATGAGCCTGTGGCTGCCTA
[2136] GCGAGGCAACCGTGTACCTGCCACCTGTGCCAGTGAGCAAGGTGGTGTCCACCG
[2137] ACGAGTATGTGGCCCGGACAAACATCTACTATCACGCAGGCACATCCAGACTGC
[2138] TGGCAGTGGGCCACCCCTACTTCCCTATCAAGAAGCCCAACAATAACAAGATCCT
[2139] GGTGCCTAAGGTGTCCGGCCTGCAGTATAGGGTGTTCCGCATCCACCTGCCAGAT
[2140] CCCAACAAGTTCGGCTTTCCTGACACCTCTTTTTACAATCCAGATACACAGAGGC
[2141] TGGTGTGGGCATGCGTGGGAGTGGAAGTGGGAAGGGGCCAGCCTCTGGGAGTGG
[2142] GAATCTCCGGACACCCACTGCTGAATAAGCTGGACGATACCGAGAACATCCCAG
[2143] TGCTGGACGAGAATGGACTGTTTGCACCAGCATCTGCCTACGCAGCAAATGCAG
[2144] GAGTGGACAACAGGGAGTGTATCAGCATGGATTATAAGCAGACCCAGCTGTGCC
[2145] TGATCGGCTGTAAGCCACCAATCGGAGAGCACTGGGGCAAGGGCTCTCCATGCA
[2146] CAAATGTGGCCGTGAACCCCGGCGATTGTCCTCCACTGGAGCTGATCAACACCGT
[2147] GATCCAGGACGGCGATATGGTGGACACAGGCTTCGGCGCCATGGACTTCACCAC
[2148] CCTGCAGGCCAATAAGAGCGAGGTGCCTCTGGACATCTGCACCTCCATCTGTAAG
[2149] TACCCCGATTATATCAAGATGGTGTCCGAGCCTTACGGCGACTCTCTGTTCTTTTA
[2150] TCTGCGGAGAGAGCAGATGTTCGTGAGGCACCTGTTTAACAGGGCAGGAGCAGT
[2151] GGGAGAGAATGTGCCAGACGATCTGTACATCAAGGGCTCCGGCTCTACCGCCAA
[2152] TCTGGCCAGCTCCAACTATTTCCCTACCCCAAGCGGCTCCATGGTGACAAGCGAC
[2153] GCCCAGATCTTTAACAAGCCATACTGGCTGCAGAGGGCACAGGGACACAATAAC
[2154] GGCATCTGCTGGGGCAACCAGCTGTTCGTGACCGTGGTGGATACCACACGCTCTA
[2155] CAAATATGAGCCTGTGCGCCGCCATCTCTACCAGCGAGACCACATACAAGAACA CAAACTTTAAGGAGTACCTGCGGCACGGCGAGGAGTATGACCTGCAGTTCATCTT
[2156] TCAGCTGTGCAAGATCACCCTGACAGCCGATGTGATGACCTACATCCACTCCATG
[2157] AACTCTACAATCCTGGAGGACTGGAATTTCGGACTGCAGCCACCTCCAGGAGGC
[2158] ACCCTGGAGGATACATATAGGTTTGTGACCTCTCAGGCCATCGCCTGTCAGAAGC
[2159] ACACACCCCCTGCCCCAAAGGAGGACCCCCTGAAGAAGTACACCTTCTGGGAAG
[2160] TGAATCTGAAGGAGAAGTTTAGCGCCGACCTGGATCAGTTCCCACTGGGACGGA
[2161] AGTTTCTGCTGCAGGCAGGCCTGAAGGCAAAGCCAAAGTTCACCCTGGGCAAGA
[2162] GAAAGGCCACCCCTACCACATCTAGCACATCCACCACAGCCAAGCGGAAGAAGA
[2163] GAAAGCTGTGAGGATCCCTCGAGCTCGGATCCTCTAGAGTCCGCAAAAATCACC
[2164] AGTCTCTCTCTACAAATCTATCTCTCTCTATTTTTCTCCAGAATAATGTGTGAGTA
[2165] GTTCCCAGATAAGGGAATTAGGGTTCTTATAGGGTTTCGCTCATGTGTTGAGCAT
[2166] ATAAGAAACCCTTAGTATGTATTTGTATTTGTAAAATACTTCTATCAATAAAATTT
[2167] CTAATTCCTAAAACCAAAATCCAGTGACCGGGCGGCCGGCCGCCCCTAGAAATA
[2168] TTTGCGACTCTTCTGGCATGTAATATTTCGTTAAATATGAAGTGCTCCATTTTTAT
[2169] TAACTTTAAATAATTGGTTGTACGATCACTTTCTTATCAAGCGTTACTAAAATGCG
[2170] TCAATCTCTTTGTTCTTCCATATTCATATGTCAAAATCTATCAAAATTCTTATATA
[2171] TCTTTTTCGAATTTGAAGTGAAATTTCGATAATTTAAAATTAAATAGAACATATC
[2172] ATTATTTAGGTGTCATATTGATTTTTATACTTAATTACTAAATTTGGTTAACTTTG
[2173] AAAGTGTACATCAACGAAAAATTAGTCAAACGACTAAAATAAATAAATATCATG
[2174] TGTTATTAAGAAAATTCTCCTATAAGAATATTTTAATAGATCATATGTTTGTAAA
[2175] AAAAATTAATTTTTACTAACACATATATTTACTTATCAAAAATTTGACAAAGTAA
[2176] GATTAAAATAATATTCATCTAACAAAAAAAAACCAGAAAATGCTGAAAACCCGG
[2177] CAAAACCGAACCAATCCAAACCGATATAGTTGGTTTGGTTTGATTTTGATATAAA
[2178] CCGAACCAACTCGGTCCATTTGCACCCCTAATCATAATAGCTTTAATATTTCAAG
[2179] ATATTATTAAGTTAACGTTGTCAATATCCTGGAAATTTTGCAAAATGAATCAAGC
[2180] CTATATGGCTGTAATATGAATTTAAAAGCAGCTCGATGTGGTGGTAATATGTAAT
[2181] TTACTTGATTCTAAAAAAATATCCCAAGTATTAATAATTTCTGCTAGGAAGAAGG
[2182] TTAGCTACGATTTACAGCAAAGCCAGAATACAAAGAACCATAAAGTGATTGAAG
[2183] CTCGAAATATACGAAGGAACAAATATTTTTAAAAAAATACGCAATGACTTGGAA
[2184] CAAAAGAAAGTGATATATTTTTTGTTCTTAAACAAGCATCCCCTCTAAAGAATGG
[2185] CAGTTTTCCTTTGCATGTAACTATTATGCTCCCTTCGTTACAAAAATTTTGGACTA
[2186] CTATTGGGCGGGTGGAGGGGGATCAGATTGTCGTTTCCCGCCTTCAGTTTAAACT
[2187] ATCAGTGTTTGACAGGATATATTGGCGGGTAAACCTAAGAGAAAAGAGCGTTTA TTAGAATAATCGGATATTTAAAAGGGCGTGAAAAGGTTTATCCGTTCGTCCATTT
[2188] GTATGTGTACATCACCGACGAGCAAGGCAAGACCGAGCGCCTTTCCGACGCTCA
[2189] CCGGGCTGGTTGCCCTCGCCGCTGGGCTGGCGGCCGTCTATGGCCCTGCAAACGC
[2190] GCCAGAAACGCCGTCGAAGCCGTGTGCGAGACACCGGCCGCCGGCGTTGTGGAT
[2191] ACCTCGCGGAAAACTTGGCCCTCACTGACAGATGAGGGGCGGACGTTGACACTT
[2192] GAGGGGCCGACTCACCCGGCGCGGCGTTGACAGATGAGGGGCAGGCTCGATTTC
[2193] GGCCGGCGACGTGGAGCTGGCCAGCCTCGCAAATCGGCGAAAACGCCTGATTTT
[2194] ACGCGAGTTTCCCACAGATGATGTGGACAAGCCTGGGGATAAGTGCCCTGCGGT
[2195] ATTGACACTTGAGGGGCGCGACTACTGACAGATGAGGGGCGCGATCCTTGACAC
[2196] TTGAGGGGCAGAGTGCTGACAGATGAGGGGCGCACCTATTGACATTTGAGGGGC
[2197] TGTCCACAGGCAGAAAATCCAGCATTTGCAAGGGTTTCCGCCCGTTTTTCGGCCA
[2198] CCGCTAACCTGTCTTTTAACCTGCTTTTAAACCAATATTTATAAACCTTGTTTTTA
[2199] ACCAGGGCTGCGCCCTGTGCGCGTGACCGCGCACGCCGAAGGGGGGTGCCCCCC
[2200] CTTCTCGAACCCTCCCGGCCCGCTAACGCGGGCCTCCCATCCCCCCAGGGGCTGC
[2201] GCCCCTCGGCCGCGAACGGCCTCACCCCAAAAATGGCAGCGCTGGCAGTCCTTG
[2202] CCATTGCCGGGATCGGGGCAGTAACGGGATGGGCGATCAGCCCGACAAGCTACC
[2203] CCTATTTGTTTATTTTTCTAAATACATTCAAATATGTATCCGCTCATGAGACAATA
[2204] ACCCTGATAAATGCTTCAATAATATTGAAAAAGGAAGAGTATGAGTATTCAACA
[2205] TTTCCGTGTCGCCCTTATTCCCTTTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCA
[2206] CCCAGAAACGCTGGTGAAAGTAAAAGATGCTGAAGATCAGTTGGGTGCACGAGT
[2207] GGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTGAGAGTTTTCGCCCC
[2208] GAAGAACGTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTAT
[2209] TATCCCGTATTGACGCCGGGCAAGAGCAACTCGGTCGCCGCATACACTATTCTCA
[2210] GAATGACTTGGTTGAGTACTCACCAGTCACAGAAAAGCATCTTACGGATGGCAT
[2211] GACAGTAAGAGAATTATGCAGTGCTGCCATAACCATGAGTGATAACACTGCGGC
[2212] CAACTTACTTCTGACAACGATCGGAGGACCGAAGGAGCTAACCGCTTTTTTGCAC
[2213] AACATGGGGGATCATGTAACTCGCCTTGATCGTTGGGAACCGGAGCTGAATGAA
[2214] GCCATACCAAACGACGAGCGTGACACCACGATGCCTGTAGCAATGGCAACAACG
[2215] TTGCGCAAACTATTAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAATTAA
[2216] TAGACTGGATGGAGGCGGATAAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTCC
[2217] GGCTGGCTGGTTTATTGCTGATAAATCTGGAGCCGGTGAGCGTGGGTCTCGCGGT
[2218] ATCATTGCAGCACTGGGGCCAGATGGTAAGCCCTCCCGTATCGTAGTTATCTACA
[2219] CGACGGGGAGTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGAGATAG GTGCCTCACTGATTAAGCATTGGTAACTGTCAGACCAAGTTTACTCATATATACT
[2220] TTAGATTGATTTAAAACTTCATTTTTAATTTAAAAGGATCTAGGTGAAGATCCTTT
[2221] TTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGTTCCACTGAGCGTC
[2222] AGACCCCGTAGAAAAGATCAAAGGATCTTCTTGAGATCCTTTTTTTCTGCGCGTA
[2223] ATCTGCTGCTTGCAAACAAAAAAACCACCGCTACCAGCGGTGGTTTGTTTGCCGG
[2224] ATCAAGAGCTACCAACTCTTTTTCCGAAGGTAACTGGCTTCAGCAGAGCGCAGAT
[2225] ACCAAATACTGTCCTTCTAGTGTAGCCGTAGTTAGGCCACCACTTCAAGAACTCT
[2226] GTAGCACCGCCTACATACCTCGCTCTGCTAATCCTGTTACCAGTGGCTGCTGCCA
[2227] GTGGCGATAAGTCGTGTCTTACCGGGTTGGACTCAAGACGATAGTTACCGGATAA
[2228] GGCGCAGCGGTCGGGCTGAACGGGGGGTTCGTGCACACAGCCCAGCTTGGAGCG
[2229] AACGACCTACACCGAACTGAGATACCTACAGCGTGAGCTATGAGAAAGCGCCAC
[2230] GCTTCCCGAAGGGAGAAAGGCGGACAGGTATCCGGTAAGCGGCAGGGTCGGAA
[2231] CAGGAGAGCGCACGAGGGAGCTTCCAGGGGGAAACGCCTGGTATCTTTATAGTC
[2232] CTGTCGGGTTTCGCCACCTCTGACTTGAGCGTCGATTTTTGTGATGCTCGTCAGGG
[2233] GGGCGGAGCCTATGGAAAAACGCCAGCAACGCGGCCTTTTTACGGTTCCTGGCCT
[2234] TTTGCTGGCCTTTTGCTCACATGGACTCTAGCTAGAGGATCACAGGCAGCAACGC
[2235] TCTGTCATCGTTACAATCAACATGCTACCCTCCGCGAGATCATCCGTGTTTCAAA
[2236] CCCGGCAGCTTAGTTGCCGTTCTTCCGAATAGCATCGGTAACATGAGCAAAGTCT
[2237] GCCGCCTTACAACGGCTCTCCCGCTGACGCCGTCCCGGACTGATGGGCTGCCTGT
[2238] ATCGAGTGGTGATTTTGTGCCGAGCTGCCGGTCGGGGAGCTGTTGGCTGGCTGGT
[2239] GGCAGGATATATTGTGGTGTAAACAAATTGACGCTTAGACAACTTAATAACACAT
[2240] TGCGGACGTTTTTAATGATCGAATACTAACGTCTCTACCAGATATCAGCTTGCAT
[2241] GCCGGTCGATCTAGTAACATAGATGACACCGCGCGCGATAATTTATCCTAGTTTG
[2242] CGCGCTATATTTTGTTTTCTATCGCGTATTAAATGTATAATTGCGGGACTCTAATC
[2243] ATAAAAACCCATCTCATAAATAACGTCATGCATTACATGTTAATTATTACATGCT
[2244] TAACGTAATTCAACAGAAATTATATGATAATCATCGCAAGACCGGCAACAGGAT
[2245] TCAATCTTAAGAAACTTTATTGCCAAATGTTTGAACGATCTGCTTGACTCTAGCTA
[2246] GAGTCCGAACCCCAGAGTCCCGCTCAGAAGAACTCGTCAAGAAGGCGATAGAAG
[2247] GCGATGCGCTGCGAATCGGGAGCGGCGATACCGTAAAGCACGAGGAAGCGGTCA
[2248] GCCCATTCGCCGCCAAGCTCTTCAGCAATATCACGGGTAGCCAACGCTATGTCCT
[2249] GATAGCGGTCCGCCACACCCAGCCGGCCACAGTCGATGAATCCAGAAAAGCGGC
[2250] CATTTTCCACCATGATATTCGGCAAGCAGGCATCGCCGTGGGTCACGACGAGATC
[2251] CTCGCCGTCGGGCATCCGCGCCTTGAGCCTGGCGAACAGTTCGGCTGGCGCGAGC CCCTGATGCTCTTCGTCCAGATCATCCTGATCGACAAGACCGGCTTCCATCCGAG
[2252] TACGTGCTCGCTCGATGCGATGTTTCGCTTGGTGGTCGAATGGGCAGGTAGCCGG
[2253] ATCAAGCGTATGCAGCCGCCGCATTGCATCAGCCATGATGGATACTTTCTCGGCA
[2254] GGAGCAAGGTGAGATGACAGGAGATCCTGCCCCGGCACTTCGCCCAATAGCAGC
[2255] CAGTTCCTTCCCGCTTCAGTGACAACGTCGAGCACAGCTGCGCAAGGAACGCCCG
[2256] TTGTGGCCAGCCACGATAGCCGCGCTGCCTCGTCTTGGAGTTCATTCAGGGCACC
[2257] GGACAGGTCGGTCTTGACAAAAAGAACCGGGCGCCCCTGCGCTGACAGCCGGAA
[2258] CACGGCGGCATCAGAGCAGCCGATTGTTTGTTGTGCCCAGTCATAGCCGAATAGC
[2259] CTCTCCACCCAAGCGGCCGGAGAACCTGCGTGCAATCCATCTTGTTCAATCATGC
[2260] CTGCATCGAGTTGAGAGTGAATATGAGACTCTAATTGGATACCGAGGGGAATTT
[2261] ATGGAACGTCAGTGGAGCATTTTTGACAAGAAATATTTGCTAGCTGATAGTGACC
[2262] TTAGGCGACTTTTGAACGCGCAATAATGGTTTCTGACGTATGTGCTTAGCTCATT
[2263] AAACTCCAGAAACCCGCGGCTCAGTGGCTCCTTCAACGTTGCGGTTCTGTCAGTT
[2264] CCAAACGTAAAACGGCTTGTCCCGCGTCATCGGCGGGGGTCATAACGTGACTCCC
[2265] TTAATTCTCCGCTCATGATCGATATCCATTGAAGAGCAAGCT
[2266] 34. SEQ ID NO: 34 - pTRAkc-rbcsl-cTP L1:2C7 DE_s (Generation II)
[2267] AATTCCGCCCCTAGAAATATTTGCGACTCTTCTGGCATGTAATATTTCGTTAAATA
[2268] TGAAGTGCTCCATTTTTATTAACTTTAAATAATTGGTTGTACGATCACTTTCTTAT
[2269] CAAGCGTTACTAAAATGCGTCAATCTCTTTGTTCTTCCATATTCATATGTCAAAAT
[2270] CTATCAAAATTCTTATATATCTTTTTCGAATTTGAAGTGAAATTTCGATAATTTAA
[2271] AATTAAATAGAACATATCATTATTTAGGTGTCATATTGATTTTTATACTTAATTAC
[2272] TAAATTTGGTTAACTTTGAAAGTGTACATCAACGAAAAATTAGTCAAACGACTAA
[2273] AATAAATAAATATCATGTGTTATTAAGAAAATTCTCCTATAAGAATATTTTAATA
[2274] GATCATATGTTTGTAAAAAAAATTAATTTTTACTAACACATATATTTACTTATCAA
[2275] AAATTTGACAAAGTAAGATTAAAATAATATTCATCTAACAAAAAAAAACCAGAA
[2276] AATGCTGAAAACCCGGCAAAACCGAACCAATCCAAACCGATATAGTTGGTTTGG
[2277] TTTGATTTTGATATAAACCGAACCAACTCGGTCCATTTGCACCCCTAATCATAAT
[2278] AGCTTTAATATTTCAAGATATTATTAAGTTAACGTTGTCAATATCCTGGAAATTTT
[2279] GCAAAATGAATCAAGCCTATATGGCTGTAATATGAATTTAAAAGCAGCTCGATGT
[2280] GGTGGTAATATGTAATTTACTTGATTCTAAAAAAATATCCCAAGTATTAATAATT
[2281] TCTGCTAGGAAGAAGGTTAGCTACGATTTACAGCAAAGCCAGAATACAAAGAAC
[2282] CATAAAGTGATTGAAGCTCGAAATATACGAAGGAACAAATATTTTTAAAAAAAT ACGCAATGACTTGGAACAAAAGAAAGTGATATATTTTTTGTTCTTAAACAAGCAT
[2283] CCCCTCTAAAGAATGGCAGTTTTCCTTTGCATGTAACTATTATGCTCCCTTCGTTA
[2284] CAAAAATTTTGGACTACTATTGGGCGCGGGGCGCGCCCGGTCCAAAGACCAGAG
[2285] GGCTATTGAGACTTTTCAACAAAGGGTAATATCGGGAAACCTCCTCGGATTCCAT
[2286] TGCCCAGCTATCTGTCACTTCATCGAAAGGACAGTAGAAAAGGAAGATGGCTTCT
[2287] ACAAATGCCATCATTGCGATAAAGGAAAGGCTATCGTTCAAGATGCCTCTACCG
[2288] ACAGTGGTCCCAAAGATGGACCCCCACCCACGAGGAACATCGTGGAAAAAGAAG
[2289] ACGTTCCAACCACGTCTTCAAAGCAAGTGGATTGATGTGATACATGGTGGAGCAC
[2290] GACACTCTCGTCTACTCCAAGAATATCAAAGATACAGTCTCAGAAGACCAGAGG
[2291] GCTATTGAGACTTTTCAACAAAGGGTAATATCGGGAAACCTCCTCGGATTCCATT
[2292] GCCCAGCTATCTGTCACTTCATCGAAAGGACAGTAGAAAAGGAAGATGGCTTCT
[2293] ACAAATGCCATCATTGCGATAAAGGAAAGGCTATCGTTCAAGATGCCTCTACCG
[2294] ACAGTGGTCCCAAAGATGGACCCCCACCCACGAGGAACATCGTGGAAAAAGAAG
[2295] ACGTTCCAACCACGTCTTCAAAGCAAGTGGATTGATGTGATATCTCCACTGACGT
[2296] AAGGGATGACGCACAATCCCACTATCCTTCGCAAGACCCTTCCTCTATATAAGGA
[2297] AGTTCATTTCATTTGGAGAGGACACGCTGAATTCACAACACAAATCAGATTTATA
[2298] GAGAGATTTATAAAAAAAAAAAAAACAATGGCTTCCTCTGTTATTTCCTCTGCAG
[2299] CTGTTGCTACACGCACCAATGTTACACAAGCTGGCAGCATGATTGCACCTTTCAC
[2300] TGGTCTCAAATCTGCTGCTACTTTCCCTGTTTCAAGGAAGCAAAACCTTGACATC
[2301] ACTTCCATTGCTAGCAATGGTGGACGCGTTAGGTTCATGAGCCTGTGGCTGCCTT
[2302] CCGAGGCAACCGTGTACCTGCCACCTGTGCCAGTGAGCAAGGTGGTGTCCACCG
[2303] ACGAGTATGTGGCCCGGACAAACATCTACTATCACGCCGGCACATCTAGACTGCT
[2304] GGCCGTGGGCCACCCCTACTTCCCTATCAAGAAGCCCAACAATAACAAGATCCTG
[2305] GTGCCTAAGGTGTCTGGCCTGCAGTATAGGGTGTTCCGCATCCACCTGCCAGATC
[2306] CCAATAAGTTCGGCTTTCCTGACACCAGCTTTTACAACCCAGATACACAGAGGCT
[2307] GGTGTGGGCATGCGTGGGAGTGGAAGTGGGAAGGGGCCAGCCTCTGGGAGTGGG
[2308] AATCTCTGGACACCCACTGCTGAATAAGCTGGACGATACCGAGATCCCAGTGCTG
[2309] GACGAGAACGGCCTGTTTGCCCCCATGGATTATAAGCAGACACAGCTGTGCCTG
[2310] ATCGGCTGTAAGCCACCAATCGGAGAGCACTGGGGCAAGGGATCCCCATGCACC
[2311] AATGTGGCCGTGAACCCCGGCGACTGTCCTCCACTGGAGCTGATCAATACCGTGA
[2312] TCCAGGACGGCGATATGGTGGACACAGGCTTCGGCGCCATGGACTTCACCACCCT
[2313] GCAGGCCAACAAGAGCGAGGTGCCTCTGGACATCTGCACCTCCATCTGTAAGTA
[2314] CCCCGATTATATCAAGATGGTGTCCGAGCCTTACGGCGATTCTCTGTTCTTTTATC TGCGGAGAGAGCAGATGTTCGTGAGGCACCTGTTTAATAGGGCAGGAGCAGTGG
[2315] GAGAGAACGTGCCAGACGATCTGTACATCAAGGGCTCCGGCTCTACCGCCAATC
[2316] TGGCCAGCTCCAACTATTTCCCTACCCCAAGCGGCTCCATGGTGACAAGCGACGC
[2317] CCAGATCTTTAATAAGCCATACTGGCTGCAGAGGGCACAGGGACACAATAACGG
[2318] CATCTGCTGGGGCAATCAGCTGTTCGTGACCGTGGTGGATACCACACGCTCTACA
[2319] AACATGAGCCTGTGCGCCGCCATCTCTACCAGCGAGACCACATACAAGAACACA
[2320] AACTTTAAGGAGTACCTGCGGCACGGCGAGGAGTATGACCTGCAGTTCATCTTTC
[2321] AGCTGTGCAAGATCACCCTGACAGCCGATGTGATGACCTACATCCACTCCATGAA
[2322] CAGCACAATCCTGGAGGACTGGAACTTCGGACTGCAGCCACCTCCAGGAGGCAC
[2323] CCTGGAGGATACATATAGGTTTGTGACCAGCCAGGCCATCGCCTGTCAGAAGCA
[2324] CACACCCCCTGCCCCAAAGGAGGACCCCCTGAAGAAGTACACCTTCTGGGAGGT
[2325] GAACCTGAAGGAGAAGTTTTCCGCCGACCTGGATCAGTTCCCACTGGGACGGAA
[2326] GTTTCTGCTGCAGGCAGGCCTGAAGGCAAAGCCAAAGTTCACCCTGGGCAAGAG
[2327] AAAGGCCACCCCTACCACATCTAGCACATCCACCACAGCCAAGCGGAAGAAGAG
[2328] AAAGCTGTGAGGATCCCTCGAGCTCGGATCCTCTAGAGTCCGCAAAAATCACCA
[2329] GTCTCTCTCTACAAATCTATCTCTCTCTATTTTTCTCCAGAATAATGTGTGAGTAG
[2330] TTCCCAGATAAGGGAATTAGGGTTCTTATAGGGTTTCGCTCATGTGTTGAGCATA
[2331] TAAGAAACCCTTAGTATGTATTTGTATTTGTAAAATACTTCTATCAATAAAATTTC
[2332] TAATTCCTAAAACCAAAATCCAGTGACCGGGCGGCCGGCCGCCCCTAGAAATAT
[2333] TTGCGACTCTTCTGGCATGTAATATTTCGTTAAATATGAAGTGCTCCATTTTTATT
[2334] AACTTTAAATAATTGGTTGTACGATCACTTTCTTATCAAGCGTTACTAAAATGCGT
[2335] CAATCTCTTTGTTCTTCCATATTCATATGTCAAAATCTATCAAAATTCTTATATAT
[2336] CTTTTTCGAATTTGAAGTGAAATTTCGATAATTTAAAATTAAATAGAACATATCA
[2337] TTATTTAGGTGTCATATTGATTTTTATACTTAATTACTAAATTTGGTTAACTTTGA
[2338] AAGTGTACATCAACGAAAAATTAGTCAAACGACTAAAATAAATAAATATCATGT
[2339] GTTATTAAGAAAATTCTCCTATAAGAATATTTTAATAGATCATATGTTTGTAAAA
[2340] AAAATTAATTTTTACTAACACATATATTTACTTATCAAAAATTTGACAAAGTAAG
[2341] ATTAAAATAATATTCATCTAACAAAAAAAAACCAGAAAATGCTGAAAACCCGGC
[2342] AAAACCGAACCAATCCAAACCGATATAGTTGGTTTGGTTTGATTTTGATATAAAC
[2343] CGAACCAACTCGGTCCATTTGCACCCCTAATCATAATAGCTTTAATATTTCAAGA
[2344] TATTATTAAGTTAACGTTGTCAATATCCTGGAAATTTTGCAAAATGAATCAAGCC
[2345] TATATGGCTGTAATATGAATTTAAAAGCAGCTCGATGTGGTGGTAATATGTAATT
[2346] TACTTGATTCTAAAAAAATATCCCAAGTATTAATAATTTCTGCTAGGAAGAAGGT TAGCTACGATTTACAGCAAAGCCAGAATACAAAGAACCATAAAGTGATTGAAGC
[2347] TCGAAATATACGAAGGAACAAATATTTTTAAAAAAATACGCAATGACTTGGAAC
[2348] AAAAGAAAGTGATATATTTTTTGTTCTTAAACAAGCATCCCCTCTAAAGAATGGC
[2349] AGTTTTCCTTTGCATGTAACTATTATGCTCCCTTCGTTACAAAAATTTTGGACTAC
[2350] TATTGGGCGGGTGGAGGGGGATCAGATTGTCGTTTCCCGCCTTCAGTTTAAACTA
[2351] TCAGTGTTTGACAGGATATATTGGCGGGTAAACCTAAGAGAAAAGAGCGTTTATT
[2352] AGAATAATCGGATATTTAAAAGGGCGTGAAAAGGTTTATCCGTTCGTCCATTTGT
[2353] ATGTGTACATCACCGACGAGCAAGGCAAGACCGAGCGCCTTTCCGACGCTCACC
[2354] GGGCTGGTTGCCCTCGCCGCTGGGCTGGCGGCCGTCTATGGCCCTGCAAACGCGC
[2355] CAGAAACGCCGTCGAAGCCGTGTGCGAGACACCGGCCGCCGGCGTTGTGGATAC
[2356] CTCGCGGAAAACTTGGCCCTCACTGACAGATGAGGGGCGGACGTTGACACTTGA
[2357] GGGGCCGACTCACCCGGCGCGGCGTTGACAGATGAGGGGCAGGCTCGATTTCGG
[2358] CCGGCGACGTGGAGCTGGCCAGCCTCGCAAATCGGCGAAAACGCCTGATTTTAC
[2359] GCGAGTTTCCCACAGATGATGTGGACAAGCCTGGGGATAAGTGCCCTGCGGTATT
[2360] GACACTTGAGGGGCGCGACTACTGACAGATGAGGGGCGCGATCCTTGACACTTG
[2361] AGGGGCAGAGTGCTGACAGATGAGGGGCGCACCTATTGACATTTGAGGGGCTGT
[2362] CCACAGGCAGAAAATCCAGCATTTGCAAGGGTTTCCGCCCGTTTTTCGGCCACCG
[2363] CTAACCTGTCTTTTAACCTGCTTTTAAACCAATATTTATAAACCTTGTTTTTAACC
[2364] AGGGCTGCGCCCTGTGCGCGTGACCGCGCACGCCGAAGGGGGGTGCCCCCCCTT
[2365] CTCGAACCCTCCCGGCCCGCTAACGCGGGCCTCCCATCCCCCCAGGGGCTGCGCC
[2366] CCTCGGCCGCGAACGGCCTCACCCCAAAAATGGCAGCGCTGGCAGTCCTTGCCAT
[2367] TGCCGGGATCGGGGCAGTAACGGGATGGGCGATCAGCCCGACAAGCTACCCCTA
[2368] TTTGTTTATTTTTCTAAATACATTCAAATATGTATCCGCTCATGAGACAATAACCC
[2369] TGATAAATGCTTCAATAATATTGAAAAAGGAAGAGTATGAGTATTCAACATTTCC
[2370] GTGTCGCCCTTATTCCCTTTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCACCCAG
[2371] AAACGCTGGTGAAAGTAAAAGATGCTGAAGATCAGTTGGGTGCACGAGTGGGTT
[2372] ACATCGAACTGGATCTCAACAGCGGTAAGATCCTTGAGAGTTTTCGCCCCGAAGA
[2373] ACGTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTATTATCCC
[2374] GTATTGACGCCGGGCAAGAGCAACTCGGTCGCCGCATACACTATTCTCAGAATG
[2375] ACTTGGTTGAGTACTCACCAGTCACAGAAAAGCATCTTACGGATGGCATGACAGT
[2376] AAGAGAATTATGCAGTGCTGCCATAACCATGAGTGATAACACTGCGGCCAACTT
[2377] ACTTCTGACAACGATCGGAGGACCGAAGGAGCTAACCGCTTTTTTGCACAACATG
[2378] GGGGATCATGTAACTCGCCTTGATCGTTGGGAACCGGAGCTGAATGAAGCCATA CCAAACGACGAGCGTGACACCACGATGCCTGTAGCAATGGCAACAACGTTGCGC
[2379] AAACTATTAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAATTAATAGACT
[2380] GGATGGAGGCGGATAAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTCCGGCTG
[2381] GCTGGTTTATTGCTGATAAATCTGGAGCCGGTGAGCGTGGGTCTCGCGGTATCAT
[2382] TGCAGCACTGGGGCCAGATGGTAAGCCCTCCCGTATCGTAGTTATCTACACGACG
[2383] GGGAGTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGAGATAGGTGCC
[2384] TCACTGATTAAGCATTGGTAACTGTCAGACCAAGTTTACTCATATATACTTTAGA
[2385] TTGATTTAAAACTTCATTTTTAATTTAAAAGGATCTAGGTGAAGATCCTTTTTGAT
[2386] AATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGTTCCACTGAGCGTCAGACC
[2387] CCGTAGAAAAGATCAAAGGATCTTCTTGAGATCCTTTTTTTCTGCGCGTAATCTG
[2388] CTGCTTGCAAACAAAAAAACCACCGCTACCAGCGGTGGTTTGTTTGCCGGATCAA
[2389] GAGCTACCAACTCTTTTTCCGAAGGTAACTGGCTTCAGCAGAGCGCAGATACCAA
[2390] ATACTGTCCTTCTAGTGTAGCCGTAGTTAGGCCACCACTTCAAGAACTCTGTAGC
[2391] ACCGCCTACATACCTCGCTCTGCTAATCCTGTTACCAGTGGCTGCTGCCAGTGGC
[2392] GATAAGTCGTGTCTTACCGGGTTGGACTCAAGACGATAGTTACCGGATAAGGCG
[2393] CAGCGGTCGGGCTGAACGGGGGGTTCGTGCACACAGCCCAGCTTGGAGCGAACG
[2394] ACCTACACCGAACTGAGATACCTACAGCGTGAGCTATGAGAAAGCGCCACGCTT
[2395] CCCGAAGGGAGAAAGGCGGACAGGTATCCGGTAAGCGGCAGGGTCGGAACAGG
[2396] AGAGCGCACGAGGGAGCTTCCAGGGGGAAACGCCTGGTATCTTTATAGTCCTGT
[2397] CGGGTTTCGCCACCTCTGACTTGAGCGTCGATTTTTGTGATGCTCGTCAGGGGGG
[2398] CGGAGCCTATGGAAAAACGCCAGCAACGCGGCCTTTTTACGGTTCCTGGCCTTTT
[2399] GCTGGCCTTTTGCTCACATGGACTCTAGCTAGAGGATCACAGGCAGCAACGCTCT
[2400] GTCATCGTTACAATCAACATGCTACCCTCCGCGAGATCATCCGTGTTTCAAACCC
[2401] GGCAGCTTAGTTGCCGTTCTTCCGAATAGCATCGGTAACATGAGCAAAGTCTGCC
[2402] GCCTTACAACGGCTCTCCCGCTGACGCCGTCCCGGACTGATGGGCTGCCTGTATC
[2403] GAGTGGTGATTTTGTGCCGAGCTGCCGGTCGGGGAGCTGTTGGCTGGCTGGTGGC
[2404] AGGATATATTGTGGTGTAAACAAATTGACGCTTAGACAACTTAATAACACATTGC
[2405] GGACGTTTTTAATGATCGAATACTAACGTCTCTACCAGATATCAGCTTGCATGCC
[2406] GGTCGATCTAGTAACATAGATGACACCGCGCGCGATAATTTATCCTAGTTTGCGC
[2407] GCTATATTTTGTTTTCTATCGCGTATTAAATGTATAATTGCGGGACTCTAATCATA
[2408] AAAACCCATCTCATAAATAACGTCATGCATTACATGTTAATTATTACATGCTTAA
[2409] CGTAATTCAACAGAAATTATATGATAATCATCGCAAGACCGGCAACAGGATTCA
[2410] ATCTTAAGAAACTTTATTGCCAAATGTTTGAACGATCTGCTTGACTCTAGCTAGA GTCCGAACCCCAGAGTCCCGCTCAGAAGAACTCGTCAAGAAGGCGATAGAAGGC
[2411] GATGCGCTGCGAATCGGGAGCGGCGATACCGTAAAGCACGAGGAAGCGGTCAGC
[2412] CCATTCGCCGCCAAGCTCTTCAGCAATATCACGGGTAGCCAACGCTATGTCCTGA
[2413] TAGCGGTCCGCCACACCCAGCCGGCCACAGTCGATGAATCCAGAAAAGCGGCCA
[2414] TTTTCCACCATGATATTCGGCAAGCAGGCATCGCCGTGGGTCACGACGAGATCCT
[2415] CGCCGTCGGGCATCCGCGCCTTGAGCCTGGCGAACAGTTCGGCTGGCGCGAGCC
[2416] CCTGATGCTCTTCGTCCAGATCATCCTGATCGACAAGACCGGCTTCCATCCGAGT
[2417] ACGTGCTCGCTCGATGCGATGTTTCGCTTGGTGGTCGAATGGGCAGGTAGCCGGA
[2418] TCAAGCGTATGCAGCCGCCGCATTGCATCAGCCATGATGGATACTTTCTCGGCAG
[2419] GAGCAAGGTGAGATGACAGGAGATCCTGCCCCGGCACTTCGCCCAATAGCAGCC
[2420] AGTTCCTTCCCGCTTCAGTGACAACGTCGAGCACAGCTGCGCAAGGAACGCCCGT
[2421] TGTGGCCAGCCACGATAGCCGCGCTGCCTCGTCTTGGAGTTCATTCAGGGCACCG
[2422] GACAGGTCGGTCTTGACAAAAAGAACCGGGCGCCCCTGCGCTGACAGCCGGAAC
[2423] ACGGCGGCATCAGAGCAGCCGATTGTTTGTTGTGCCCAGTCATAGCCGAATAGCC
[2424] TCTCCACCCAAGCGGCCGGAGAACCTGCGTGCAATCCATCTTGTTCAATCATGCC
[2425] TGCATCGAGTTGAGAGTGAATATGAGACTCTAATTGGATACCGAGGGGAATTTAT
[2426] GGAACGTCAGTGGAGCATTTTTGACAAGAAATATTTGCTAGCTGATAGTGACCTT
[2427] AGGCGACTTTTGAACGCGCAATAATGGTTTCTGACGTATGTGCTTAGCTCATTAA
[2428] ACTCCAGAAACCCGCGGCTCAGTGGCTCCTTCAACGTTGCGGTTCTGTCAGTTCC
[2429] AAACGTAAAACGGCTTGTCCCGCGTCATCGGCGGGGGTCATAACGTGACTCCCTT
[2430] AATTCTCCGCTCATGATCGATATCCATTGAAGAGCAAGCT
[2431] 35. SEQ ID NO: 35 - pTRAkc-rbcsl-cTP L1:2C7 h4_i (Generation II)
[2432] AATTCCGCCCCTAGAAATATTTGCGACTCTTCTGGCATGTAATATTTCGTTAAATA
[2433] TGAAGTGCTCCATTTTTATTAACTTTAAATAATTGGTTGTACGATCACTTTCTTAT
[2434] CAAGCGTTACTAAAATGCGTCAATCTCTTTGTTCTTCCATATTCATATGTCAAAAT
[2435] CTATCAAAATTCTTATATATCTTTTTCGAATTTGAAGTGAAATTTCGATAATTTAA
[2436] AATTAAATAGAACATATCATTATTTAGGTGTCATATTGATTTTTATACTTAATTAC
[2437] TAAATTTGGTTAACTTTGAAAGTGTACATCAACGAAAAATTAGTCAAACGACTAA
[2438] AATAAATAAATATCATGTGTTATTAAGAAAATTCTCCTATAAGAATATTTTAATA
[2439] GATCATATGTTTGTAAAAAAAATTAATTTTTACTAACACATATATTTACTTATCAA
[2440] AAATTTGACAAAGTAAGATTAAAATAATATTCATCTAACAAAAAAAAACCAGAA
[2441] AATGCTGAAAACCCGGCAAAACCGAACCAATCCAAACCGATATAGTTGGTTTGG TTTGATTTTGATATAAACCGAACCAACTCGGTCCATTTGCACCCCTAATCATAAT
[2442] AGCTTTAATATTTCAAGATATTATTAAGTTAACGTTGTCAATATCCTGGAAATTTT
[2443] GCAAAATGAATCAAGCCTATATGGCTGTAATATGAATTTAAAAGCAGCTCGATGT
[2444] GGTGGTAATATGTAATTTACTTGATTCTAAAAAAATATCCCAAGTATTAATAATT
[2445] TCTGCTAGGAAGAAGGTTAGCTACGATTTACAGCAAAGCCAGAATACAAAGAAC
[2446] CATAAAGTGATTGAAGCTCGAAATATACGAAGGAACAAATATTTTTAAAAAAAT
[2447] ACGCAATGACTTGGAACAAAAGAAAGTGATATATTTTTTGTTCTTAAACAAGCAT
[2448] CCCCTCTAAAGAATGGCAGTTTTCCTTTGCATGTAACTATTATGCTCCCTTCGTTA
[2449] CAAAAATTTTGGACTACTATTGGGCGCGGGGCGCGCCCGGTCCAAAGACCAGAG
[2450] GGCTATTGAGACTTTTCAACAAAGGGTAATATCGGGAAACCTCCTCGGATTCCAT
[2451] TGCCCAGCTATCTGTCACTTCATCGAAAGGACAGTAGAAAAGGAAGATGGCTTCT
[2452] ACAAATGCCATCATTGCGATAAAGGAAAGGCTATCGTTCAAGATGCCTCTACCG
[2453] ACAGTGGTCCCAAAGATGGACCCCCACCCACGAGGAACATCGTGGAAAAAGAAG
[2454] ACGTTCCAACCACGTCTTCAAAGCAAGTGGATTGATGTGATACATGGTGGAGCAC
[2455] GACACTCTCGTCTACTCCAAGAATATCAAAGATACAGTCTCAGAAGACCAGAGG
[2456] GCTATTGAGACTTTTCAACAAAGGGTAATATCGGGAAACCTCCTCGGATTCCATT
[2457] GCCCAGCTATCTGTCACTTCATCGAAAGGACAGTAGAAAAGGAAGATGGCTTCT
[2458] ACAAATGCCATCATTGCGATAAAGGAAAGGCTATCGTTCAAGATGCCTCTACCG
[2459] ACAGTGGTCCCAAAGATGGACCCCCACCCACGAGGAACATCGTGGAAAAAGAAG
[2460] ACGTTCCAACCACGTCTTCAAAGCAAGTGGATTGATGTGATATCTCCACTGACGT
[2461] AAGGGATGACGCACAATCCCACTATCCTTCGCAAGACCCTTCCTCTATATAAGGA
[2462] AGTTCATTTCATTTGGAGAGGACACGCTGAATTCACAACACAAATCAGATTTATA
[2463] GAGAGATTTATAAAAAAAAAAAAAACAATGGCTTCCTCTGTTATTTCCTCTGCAG
[2464] CTGTTGCTACACGCACCAATGTTACACAAGCTGGCAGCATGATTGCACCTTTCAC
[2465] TGGTCTCAAATCTGCTGCTACTTTCCCTGTTTCAAGGAAGCAAAACCTTGACATC
[2466] ACTTCCATTGCTAGCAATGGTGGACGCGTTAGGTTCATGAGCCTGTGGCTGCCTT
[2467] CCGAGGCAACCGTGTACCTGCCACCTGTGCCAGTGAGCAAGGTGGTGTCCACCG
[2468] ATGAGTATGTGGCCCGGACAAATATCTACTATCACGCCGGCACATCTAGACTGCT
[2469] GGCCGTGGGCCACCCCTACTTCCCTATCAAGAAGCCCAACAATAACAAGATCCTG
[2470] GTGCCTAAGGTGTCTGGCCTGCAGTATAGGGTGTTCCGCATCCACCTGCCAGACC
[2471] CCAATAAGTTCGGCTTTCCTGACACCAGCTTTTACAACCCAGATACACAGAGGCT
[2472] GGTGTGGGCATGCGTGGGAGTGGAAGTGGGAAGGGGCCAGCCTCTGGGAGTGGG
[2473] AATCTCTGGACACCCACTGCTGAATAAGCTGGACGATACCGAGAACGCCAGCGC CTACGCAGCAAATGCAGGAGTGGACAACAGGGAGTGTATCTCCATGGATTATAA
[2474] GCAGACCCAGCTGTGCCTGATCGGCTGTAAGCCACCAATCGGAGAGCACTGGGG
[2475] CAAGGGCTCTCCATGCACAAATGTGGCCGTGAACCCCGGCGATTGTCCTCCACTG
[2476] GAGCTGATCAATACCGTGATCCAGGACGGCGATATGGTGGACACAGGCTTCGGC
[2477] GCCATGGACTTCACCACCCTGCAGGCCAACAAGAGCGAGGTGCCTCTGGACATC
[2478] TGCACCTCCATCTGTAAGTACCCCGATTATATCAAGATGGTGTCCGAGCCTTACG
[2479] GCGACTCTCTGTTCTTTTATCTGCGGAGAGAGCAGATGTTCGTGAGGCACCTGTT
[2480] TAATAGGGCAGGAGCAGTGGGAGAGAACGTGCCAGACGATCTGTACATCAAGGG
[2481] CTCCGGCTCTACCGCCAATCTGGCCAGCTCCAACTATTTCCCTACCCCAAGCGGC
[2482] TCCATGGTGACAAGCGATGCCCAGATCTTTAACAAGCCATACTGGCTGCAGAGG
[2483] GCACAGGGACACAATAACGGCATCTGCTGGGGCAATCAGCTGTTCGTGACCGTG
[2484] GTGGACACCACACGCTCTACAAACATGAGCCTGTGCGCCGCCATCTCTACCAGCG
[2485] AGACCACATACAAGAACACAAACTTTAAGGAGTACCTGCGGCACGGCGAGGAGT
[2486] ATGACCTGCAGTTCATCTTTCAGCTGTGCAAGATCACCCTGACAGCCGATGTGAT
[2487] GACCTACATCCACTCCATGAACAGCACAATCCTGGAGGACTGGAACTTCGGACT
[2488] GCAGCCACCTCCAGGAGGCACCCTGATCCCAGTGCTGGACGAGAATGGCCTGTT
[2489] CGCCCCCGAGGATACCTATAGGTTTGTGACAAGCCAGGCCATCGCATGTCAGAA
[2490] GCACACCCCACCTGCACCAAAGGAGGACCCCCTGAAGAAGTACACATTCTGGGA
[2491] GGTGAACCTGAAGGAGAAGTTTTCCGCCGACCTGGATCAGTTCCCACTGGGACG
[2492] GAAGTTTCTGCTGCAGGCAGGCCTGAAGGCAAAGCCAAAGTTTACCCTGGGCAA
[2493] GAGAAAGGCCACCCCTACCACATCTAGCACATCCACCACAGCCAAGCGGAAGAA
[2494] GAGAAAGCTGTGAGGATCCCTCGAGCTCGGATCCTCTAGAGTCCGCAAAAATCA
[2495] CCAGTCTCTCTCTACAAATCTATCTCTCTCTATTTTTCTCCAGAATAATGTGTGAG
[2496] TAGTTCCCAGATAAGGGAATTAGGGTTCTTATAGGGTTTCGCTCATGTGTTGAGC
[2497] ATATAAGAAACCCTTAGTATGTATTTGTATTTGTAAAATACTTCTATCAATAAAA
[2498] TTTCTAATTCCTAAAACCAAAATCCAGTGACCGGGCGGCCGGCCGCCCCTAGAAA
[2499] TATTTGCGACTCTTCTGGCATGTAATATTTCGTTAAATATGAAGTGCTCCATTTTT
[2500] ATTAACTTTAAATAATTGGTTGTACGATCACTTTCTTATCAAGCGTTACTAAAATG
[2501] CGTCAATCTCTTTGTTCTTCCATATTCATATGTCAAAATCTATCAAAATTCTTATA
[2502] TATCTTTTTCGAATTTGAAGTGAAATTTCGATAATTTAAAATTAAATAGAACATA
[2503] TCATTATTTAGGTGTCATATTGATTTTTATACTTAATTACTAAATTTGGTTAACTTT
[2504] GAAAGTGTACATCAACGAAAAATTAGTCAAACGACTAAAATAAATAAATATCAT
[2505] GTGTTATTAAGAAAATTCTCCTATAAGAATATTTTAATAGATCATATGTTTGTAA AAAAAATTAATTTTTACTAACACATATATTTACTTATCAAAAATTTGACAAAGTA
[2506] AGATTAAAATAATATTCATCTAACAAAAAAAAACCAGAAAATGCTGAAAACCCG
[2507] GCAAAACCGAACCAATCCAAACCGATATAGTTGGTTTGGTTTGATTTTGATATAA
[2508] ACCGAACCAACTCGGTCCATTTGCACCCCTAATCATAATAGCTTTAATATTTCAA
[2509] GATATTATTAAGTTAACGTTGTCAATATCCTGGAAATTTTGCAAAATGAATCAAG
[2510] CCTATATGGCTGTAATATGAATTTAAAAGCAGCTCGATGTGGTGGTAATATGTAA
[2511] TTTACTTGATTCTAAAAAAATATCCCAAGTATTAATAATTTCTGCTAGGAAGAAG
[2512] GTTAGCTACGATTTACAGCAAAGCCAGAATACAAAGAACCATAAAGTGATTGAA
[2513] GCTCGAAATATACGAAGGAACAAATATTTTTAAAAAAATACGCAATGACTTGGA
[2514] ACAAAAGAAAGTGATATATTTTTTGTTCTTAAACAAGCATCCCCTCTAAAGAATG
[2515] GCAGTTTTCCTTTGCATGTAACTATTATGCTCCCTTCGTTACAAAAATTTTGGACT
[2516] ACTATTGGGCGGGTGGAGGGGGATCAGATTGTCGTTTCCCGCCTTCAGTTTAAAC
[2517] TATCAGTGTTTGACAGGATATATTGGCGGGTAAACCTAAGAGAAAAGAGCGTTT
[2518] ATTAGAATAATCGGATATTTAAAAGGGCGTGAAAAGGTTTATCCGTTCGTCCATT
[2519] TGTATGTGTACATCACCGACGAGCAAGGCAAGACCGAGCGCCTTTCCGACGCTC
[2520] ACCGGGCTGGTTGCCCTCGCCGCTGGGCTGGCGGCCGTCTATGGCCCTGCAAACG
[2521] CGCCAGAAACGCCGTCGAAGCCGTGTGCGAGACACCGGCCGCCGGCGTTGTGGA
[2522] TACCTCGCGGAAAACTTGGCCCTCACTGACAGATGAGGGGCGGACGTTGACACT
[2523] TGAGGGGCCGACTCACCCGGCGCGGCGTTGACAGATGAGGGGCAGGCTCGATTT
[2524] CGGCCGGCGACGTGGAGCTGGCCAGCCTCGCAAATCGGCGAAAACGCCTGATTT
[2525] TACGCGAGTTTCCCACAGATGATGTGGACAAGCCTGGGGATAAGTGCCCTGCGG
[2526] TATTGACACTTGAGGGGCGCGACTACTGACAGATGAGGGGCGCGATCCTTGACA
[2527] CTTGAGGGGCAGAGTGCTGACAGATGAGGGGCGCACCTATTGACATTTGAGGGG
[2528] CTGTCCACAGGCAGAAAATCCAGCATTTGCAAGGGTTTCCGCCCGTTTTTCGGCC
[2529] ACCGCTAACCTGTCTTTTAACCTGCTTTTAAACCAATATTTATAAACCTTGTTTTT
[2530] AACCAGGGCTGCGCCCTGTGCGCGTGACCGCGCACGCCGAAGGGGGGTGCCCCC
[2531] CCTTCTCGAACCCTCCCGGCCCGCTAACGCGGGCCTCCCATCCCCCCAGGGGCTG
[2532] CGCCCCTCGGCCGCGAACGGCCTCACCCCAAAAATGGCAGCGCTGGCAGTCCTT
[2533] GCCATTGCCGGGATCGGGGCAGTAACGGGATGGGCGATCAGCCCGACAAGCTAC
[2534] CCCTATTTGTTTATTTTTCTAAATACATTCAAATATGTATCCGCTCATGAGACAAT
[2535] AACCCTGATAAATGCTTCAATAATATTGAAAAAGGAAGAGTATGAGTATTCAAC
[2536] ATTTCCGTGTCGCCCTTATTCCCTTTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTC
[2537] ACCCAGAAACGCTGGTGAAAGTAAAAGATGCTGAAGATCAGTTGGGTGCACGAG TGGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTGAGAGTTTTCGCCC
[2538] CGAAGAACGTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTA
[2539] TTATCCCGTATTGACGCCGGGCAAGAGCAACTCGGTCGCCGCATACACTATTCTC
[2540] AGAATGACTTGGTTGAGTACTCACCAGTCACAGAAAAGCATCTTACGGATGGCA
[2541] TGACAGTAAGAGAATTATGCAGTGCTGCCATAACCATGAGTGATAACACTGCGG
[2542] CCAACTTACTTCTGACAACGATCGGAGGACCGAAGGAGCTAACCGCTTTTTTGCA
[2543] CAACATGGGGGATCATGTAACTCGCCTTGATCGTTGGGAACCGGAGCTGAATGA
[2544] AGCCATACCAAACGACGAGCGTGACACCACGATGCCTGTAGCAATGGCAACAAC
[2545] GTTGCGCAAACTATTAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAATTA
[2546] ATAGACTGGATGGAGGCGGATAAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTC
[2547] CGGCTGGCTGGTTTATTGCTGATAAATCTGGAGCCGGTGAGCGTGGGTCTCGCGG
[2548] TATCATTGCAGCACTGGGGCCAGATGGTAAGCCCTCCCGTATCGTAGTTATCTAC
[2549] ACGACGGGGAGTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGAGATA
[2550] GGTGCCTCACTGATTAAGCATTGGTAACTGTCAGACCAAGTTTACTCATATATAC
[2551] TTTAGATTGATTTAAAACTTCATTTTTAATTTAAAAGGATCTAGGTGAAGATCCTT
[2552] TTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGTTCCACTGAGCGTC
[2553] AGACCCCGTAGAAAAGATCAAAGGATCTTCTTGAGATCCTTTTTTTCTGCGCGTA
[2554] ATCTGCTGCTTGCAAACAAAAAAACCACCGCTACCAGCGGTGGTTTGTTTGCCGG
[2555] ATCAAGAGCTACCAACTCTTTTTCCGAAGGTAACTGGCTTCAGCAGAGCGCAGAT
[2556] ACCAAATACTGTCCTTCTAGTGTAGCCGTAGTTAGGCCACCACTTCAAGAACTCT
[2557] GTAGCACCGCCTACATACCTCGCTCTGCTAATCCTGTTACCAGTGGCTGCTGCCA
[2558] GTGGCGATAAGTCGTGTCTTACCGGGTTGGACTCAAGACGATAGTTACCGGATAA
[2559] GGCGCAGCGGTCGGGCTGAACGGGGGGTTCGTGCACACAGCCCAGCTTGGAGCG
[2560] AACGACCTACACCGAACTGAGATACCTACAGCGTGAGCTATGAGAAAGCGCCAC
[2561] GCTTCCCGAAGGGAGAAAGGCGGACAGGTATCCGGTAAGCGGCAGGGTCGGAA
[2562] CAGGAGAGCGCACGAGGGAGCTTCCAGGGGGAAACGCCTGGTATCTTTATAGTC
[2563] CTGTCGGGTTTCGCCACCTCTGACTTGAGCGTCGATTTTTGTGATGCTCGTCAGGG
[2564] GGGCGGAGCCTATGGAAAAACGCCAGCAACGCGGCCTTTTTACGGTTCCTGGCCT
[2565] TTTGCTGGCCTTTTGCTCACATGGACTCTAGCTAGAGGATCACAGGCAGCAACGC
[2566] TCTGTCATCGTTACAATCAACATGCTACCCTCCGCGAGATCATCCGTGTTTCAAA
[2567] CCCGGCAGCTTAGTTGCCGTTCTTCCGAATAGCATCGGTAACATGAGCAAAGTCT
[2568] GCCGCCTTACAACGGCTCTCCCGCTGACGCCGTCCCGGACTGATGGGCTGCCTGT
[2569] ATCGAGTGGTGATTTTGTGCCGAGCTGCCGGTCGGGGAGCTGTTGGCTGGCTGGT GGCAGGATATATTGTGGTGTAAACAAATTGACGCTTAGACAACTTAATAACACAT
[2570] TGCGGACGTTTTTAATGATCGAATACTAACGTCTCTACCAGATATCAGCTTGCAT
[2571] GCCGGTCGATCTAGTAACATAGATGACACCGCGCGCGATAATTTATCCTAGTTTG
[2572] CGCGCTATATTTTGTTTTCTATCGCGTATTAAATGTATAATTGCGGGACTCTAATC
[2573] ATAAAAACCCATCTCATAAATAACGTCATGCATTACATGTTAATTATTACATGCT
[2574] TAACGTAATTCAACAGAAATTATATGATAATCATCGCAAGACCGGCAACAGGAT
[2575] TCAATCTTAAGAAACTTTATTGCCAAATGTTTGAACGATCTGCTTGACTCTAGCTA
[2576] GAGTCCGAACCCCAGAGTCCCGCTCAGAAGAACTCGTCAAGAAGGCGATAGAAG
[2577] GCGATGCGCTGCGAATCGGGAGCGGCGATACCGTAAAGCACGAGGAAGCGGTCA
[2578] GCCCATTCGCCGCCAAGCTCTTCAGCAATATCACGGGTAGCCAACGCTATGTCCT
[2579] GATAGCGGTCCGCCACACCCAGCCGGCCACAGTCGATGAATCCAGAAAAGCGGC
[2580] CATTTTCCACCATGATATTCGGCAAGCAGGCATCGCCGTGGGTCACGACGAGATC
[2581] CTCGCCGTCGGGCATCCGCGCCTTGAGCCTGGCGAACAGTTCGGCTGGCGCGAGC
[2582] CCCTGATGCTCTTCGTCCAGATCATCCTGATCGACAAGACCGGCTTCCATCCGAG
[2583] TACGTGCTCGCTCGATGCGATGTTTCGCTTGGTGGTCGAATGGGCAGGTAGCCGG
[2584] ATCAAGCGTATGCAGCCGCCGCATTGCATCAGCCATGATGGATACTTTCTCGGCA
[2585] GGAGCAAGGTGAGATGACAGGAGATCCTGCCCCGGCACTTCGCCCAATAGCAGC
[2586] CAGTTCCTTCCCGCTTCAGTGACAACGTCGAGCACAGCTGCGCAAGGAACGCCCG
[2587] TTGTGGCCAGCCACGATAGCCGCGCTGCCTCGTCTTGGAGTTCATTCAGGGCACC
[2588] GGACAGGTCGGTCTTGACAAAAAGAACCGGGCGCCCCTGCGCTGACAGCCGGAA
[2589] CACGGCGGCATCAGAGCAGCCGATTGTTTGTTGTGCCCAGTCATAGCCGAATAGC
[2590] CTCTCCACCCAAGCGGCCGGAGAACCTGCGTGCAATCCATCTTGTTCAATCATGC
[2591] CTGCATCGAGTTGAGAGTGAATATGAGACTCTAATTGGATACCGAGGGGAATTT
[2592] ATGGAACGTCAGTGGAGCATTTTTGACAAGAAATATTTGCTAGCTGATAGTGACC
[2593] TTAGGCGACTTTTGAACGCGCAATAATGGTTTCTGACGTATGTGCTTAGCTCATT
[2594] AAACTCCAGAAACCCGCGGCTCAGTGGCTCCTTCAACGTTGCGGTTCTGTCAGTT
[2595] CCAAACGTAAAACGGCTTGTCCCGCGTCATCGGCGGGGGTCATAACGTGACTCCC
[2596] TTAATTCTCCGCTCATGATCGATATCCATTGAAGAGCAAGCT
[2597] 36. SEQ ID NO: 36 - pTRAkc-rbcsl-cTP L1:2C7 h4_s (Generation II)
[2598] AATTCCGCCCCTAGAAATATTTGCGACTCTTCTGGCATGTAATATTTCGTTAAATA
[2599] TGAAGTGCTCCATTTTTATTAACTTTAAATAATTGGTTGTACGATCACTTTCTTAT
[2600] CAAGCGTTACTAAAATGCGTCAATCTCTTTGTTCTTCCATATTCATATGTCAAAAT CTATCAAAATTCTTATATATCTTTTTCGAATTTGAAGTGAAATTTCGATAATTTAA
[2601] AATTAAATAGAACATATCATTATTTAGGTGTCATATTGATTTTTATACTTAATTAC
[2602] TAAATTTGGTTAACTTTGAAAGTGTACATCAACGAAAAATTAGTCAAACGACTAA
[2603] AATAAATAAATATCATGTGTTATTAAGAAAATTCTCCTATAAGAATATTTTAATA
[2604] GATCATATGTTTGTAAAAAAAATTAATTTTTACTAACACATATATTTACTTATCAA
[2605] AAATTTGACAAAGTAAGATTAAAATAATATTCATCTAACAAAAAAAAACCAGAA
[2606] AATGCTGAAAACCCGGCAAAACCGAACCAATCCAAACCGATATAGTTGGTTTGG
[2607] TTTGATTTTGATATAAACCGAACCAACTCGGTCCATTTGCACCCCTAATCATAAT
[2608] AGCTTTAATATTTCAAGATATTATTAAGTTAACGTTGTCAATATCCTGGAAATTTT
[2609] GCAAAATGAATCAAGCCTATATGGCTGTAATATGAATTTAAAAGCAGCTCGATGT
[2610] GGTGGTAATATGTAATTTACTTGATTCTAAAAAAATATCCCAAGTATTAATAATT
[2611] TCTGCTAGGAAGAAGGTTAGCTACGATTTACAGCAAAGCCAGAATACAAAGAAC
[2612] CATAAAGTGATTGAAGCTCGAAATATACGAAGGAACAAATATTTTTAAAAAAAT
[2613] ACGCAATGACTTGGAACAAAAGAAAGTGATATATTTTTTGTTCTTAAACAAGCAT
[2614] CCCCTCTAAAGAATGGCAGTTTTCCTTTGCATGTAACTATTATGCTCCCTTCGTTA
[2615] CAAAAATTTTGGACTACTATTGGGCGCGGGGCGCGCCCGGTCCAAAGACCAGAG
[2616] GGCTATTGAGACTTTTCAACAAAGGGTAATATCGGGAAACCTCCTCGGATTCCAT
[2617] TGCCCAGCTATCTGTCACTTCATCGAAAGGACAGTAGAAAAGGAAGATGGCTTCT
[2618] ACAAATGCCATCATTGCGATAAAGGAAAGGCTATCGTTCAAGATGCCTCTACCG
[2619] ACAGTGGTCCCAAAGATGGACCCCCACCCACGAGGAACATCGTGGAAAAAGAAG
[2620] ACGTTCCAACCACGTCTTCAAAGCAAGTGGATTGATGTGATACATGGTGGAGCAC
[2621] GACACTCTCGTCTACTCCAAGAATATCAAAGATACAGTCTCAGAAGACCAGAGG
[2622] GCTATTGAGACTTTTCAACAAAGGGTAATATCGGGAAACCTCCTCGGATTCCATT
[2623] GCCCAGCTATCTGTCACTTCATCGAAAGGACAGTAGAAAAGGAAGATGGCTTCT
[2624] ACAAATGCCATCATTGCGATAAAGGAAAGGCTATCGTTCAAGATGCCTCTACCG
[2625] ACAGTGGTCCCAAAGATGGACCCCCACCCACGAGGAACATCGTGGAAAAAGAAG
[2626] ACGTTCCAACCACGTCTTCAAAGCAAGTGGATTGATGTGATATCTCCACTGACGT
[2627] AAGGGATGACGCACAATCCCACTATCCTTCGCAAGACCCTTCCTCTATATAAGGA
[2628] AGTTCATTTCATTTGGAGAGGACACGCTGAATTCACAACACAAATCAGATTTATA
[2629] GAGAGATTTATAAAAAAAAAAAAAACAATGGCTTCCTCTGTTATTTCCTCTGCAG
[2630] CTGTTGCTACACGCACCAATGTTACACAAGCTGGCAGCATGATTGCACCTTTCAC
[2631] TGGTCTCAAATCTGCTGCTACTTTCCCTGTTTCAAGGAAGCAAAACCTTGACATC
[2632] ACTTCCATTGCTAGCAATGGTGGACGCGTTAGGTTCATGAGCCTGTGGCTGCCTT CCGAGGCCACAGTGTACCTGCCCCCTGTGCCAGTGAGCAAGGTGGTGTCCACCG
[2633] ATGAGTATGTGGCCCGGACAAATATCTACTATCACGCAGGCACCTCTAGACTGCT
[2634] GGCAGTGGGCCACCCCTACTTCCCTATCAAGAAGCCCAACAATAACAAGATCCT
[2635] GGTGCCTAAGGTGTCTGGCCTGCAGTATAGGGTGTTCCGCATCCACCTGCCAGAC
[2636] CCCAATAAGTTCGGCTTTCCTGACACCAGCTTTTACAACCCAGATACACAGAGGC
[2637] TGGTGTGGGCATGCGTGGGAGTGGAAGTGGGAAGGGGCCAGCCTCTGGGAGTGG
[2638] GAATCTCTGGACACCCACTGCTGAATAAGCTGGACGATACCGAGAACGCCAGCG
[2639] CCTACGCAGCAAATGCAGGAGTGGACAACAGGGAGTGTATCTCCATGGATTATA
[2640] AGCAGACACAGCTGTGCCTGATCGGCTGTAAGCCACCAATCGGAGAGCACTGGG
[2641] GCAAGGGATCCCCATGCACCAATGTGGCCGTGAACCCCGGCGATTGTCCTCCACT
[2642] GGAGCTGATCAATACCGTGATCCAGGACGGCGATATGGTGGACACAGGCTTCGG
[2643] CGCCATGGACTTCACCACCCTGCAGGCCAACAAGAGCGAGGTGCCTCTGGACAT
[2644] CTGCACCTCCATCTGTAAGTACCCCGATTATATCAAGATGGTGTCCGAGCCTTAC
[2645] GGCGACTCTCTGTTCTTTTATCTGCGGAGAGAGCAGATGTTCGTGAGGCACCTGT
[2646] TTAATAGGGCAGGAGCAGTGGGAGAGAACGTGCCAGACGATCTGTACATCAAGG
[2647] GCTCCGGCTCTACCGCCAATCTGGCCAGCTCCAACTATTTCCCTACCCCAAGCGG
[2648] CTCCATGGTGACAAGCGATGCCCAGATCTTTAACAAGCCCTATTGGCTGCAGAGG
[2649] GCCCAGGGCCACAATAACGGCATCTGCTGGGGCAATCAGCTGTTCGTGACCGTG
[2650] GTGGACACCACACGCTCTACAAACATGAGCCTGTGCGCCGCCATCTCTACCAGCG
[2651] AGACCACATACAAGAACACAAACTTTAAGGAGTACCTGAGGCACGGCGAGGAGT
[2652] ATGACCTGCAGTTCATCTTTCAGCTGTGCAAGATCACCCTGACAGCCGATGTGAT
[2653] GACCTACATCCACTCCATGAACAGCACAATCCTGGAGGACTGGAACTTCGGACT
[2654] GCAGCCACCTCCAGGAGGAACCATCCCAGTGCTGGATGAGAATGGACTGTTTGC
[2655] ACCAACACCACCTGCACCAAAGGAGGACCCCCTGAAGAAGTACACCTTCTGGGA
[2656] GGTGAACCTGAAGGAGAAGTTTTCCGCCGACCTGGATCAGTTCCCACTGGGACG
[2657] GAAGTTTCTGCTGCAGGCAGGCCTGAAGGCAAAGCCAAAGTTCACCCTGGGCAA
[2658] GAGAAAGGCCACCCCTACCACATCTAGCACAAGCACCACAGCCAAGCGGAAGAA
[2659] GAGAAAGCTGTGAGGATCCCTCGAGCTCGGATCCTCTAGAGTCCGCAAAAATCA
[2660] CCAGTCTCTCTCTACAAATCTATCTCTCTCTATTTTTCTCCAGAATAATGTGTGAG
[2661] TAGTTCCCAGATAAGGGAATTAGGGTTCTTATAGGGTTTCGCTCATGTGTTGAGC
[2662] ATATAAGAAACCCTTAGTATGTATTTGTATTTGTAAAATACTTCTATCAATAAAA
[2663] TTTCTAATTCCTAAAACCAAAATCCAGTGACCGGGCGGCCGGCCGCCCCTAGAAA
[2664] TATTTGCGACTCTTCTGGCATGTAATATTTCGTTAAATATGAAGTGCTCCATTTTT ATTAACTTTAAATAATTGGTTGTACGATCACTTTCTTATCAAGCGTTACTAAAATG
[2665] CGTCAATCTCTTTGTTCTTCCATATTCATATGTCAAAATCTATCAAAATTCTTATA
[2666] TATCTTTTTCGAATTTGAAGTGAAATTTCGATAATTTAAAATTAAATAGAACATA
[2667] TCATTATTTAGGTGTCATATTGATTTTTATACTTAATTACTAAATTTGGTTAACTTT
[2668] GAAAGTGTACATCAACGAAAAATTAGTCAAACGACTAAAATAAATAAATATCAT
[2669] GTGTTATTAAGAAAATTCTCCTATAAGAATATTTTAATAGATCATATGTTTGTAA
[2670] AAAAAATTAATTTTTACTAACACATATATTTACTTATCAAAAATTTGACAAAGTA
[2671] AGATTAAAATAATATTCATCTAACAAAAAAAAACCAGAAAATGCTGAAAACCCG
[2672] GCAAAACCGAACCAATCCAAACCGATATAGTTGGTTTGGTTTGATTTTGATATAA
[2673] ACCGAACCAACTCGGTCCATTTGCACCCCTAATCATAATAGCTTTAATATTTCAA
[2674] GATATTATTAAGTTAACGTTGTCAATATCCTGGAAATTTTGCAAAATGAATCAAG
[2675] CCTATATGGCTGTAATATGAATTTAAAAGCAGCTCGATGTGGTGGTAATATGTAA
[2676] TTTACTTGATTCTAAAAAAATATCCCAAGTATTAATAATTTCTGCTAGGAAGAAG
[2677] GTTAGCTACGATTTACAGCAAAGCCAGAATACAAAGAACCATAAAGTGATTGAA
[2678] GCTCGAAATATACGAAGGAACAAATATTTTTAAAAAAATACGCAATGACTTGGA
[2679] ACAAAAGAAAGTGATATATTTTTTGTTCTTAAACAAGCATCCCCTCTAAAGAATG
[2680] GCAGTTTTCCTTTGCATGTAACTATTATGCTCCCTTCGTTACAAAAATTTTGGACT
[2681] ACTATTGGGCGGGTGGAGGGGGATCAGATTGTCGTTTCCCGCCTTCAGTTTAAAC
[2682] TATCAGTGTTTGACAGGATATATTGGCGGGTAAACCTAAGAGAAAAGAGCGTTT
[2683] ATTAGAATAATCGGATATTTAAAAGGGCGTGAAAAGGTTTATCCGTTCGTCCATT
[2684] TGTATGTGTACATCACCGACGAGCAAGGCAAGACCGAGCGCCTTTCCGACGCTC
[2685] ACCGGGCTGGTTGCCCTCGCCGCTGGGCTGGCGGCCGTCTATGGCCCTGCAAACG
[2686] CGCCAGAAACGCCGTCGAAGCCGTGTGCGAGACACCGGCCGCCGGCGTTGTGGA
[2687] TACCTCGCGGAAAACTTGGCCCTCACTGACAGATGAGGGGCGGACGTTGACACT
[2688] TGAGGGGCCGACTCACCCGGCGCGGCGTTGACAGATGAGGGGCAGGCTCGATTT
[2689] CGGCCGGCGACGTGGAGCTGGCCAGCCTCGCAAATCGGCGAAAACGCCTGATTT
[2690] TACGCGAGTTTCCCACAGATGATGTGGACAAGCCTGGGGATAAGTGCCCTGCGG
[2691] TATTGACACTTGAGGGGCGCGACTACTGACAGATGAGGGGCGCGATCCTTGACA
[2692] CTTGAGGGGCAGAGTGCTGACAGATGAGGGGCGCACCTATTGACATTTGAGGGG
[2693] CTGTCCACAGGCAGAAAATCCAGCATTTGCAAGGGTTTCCGCCCGTTTTTCGGCC
[2694] ACCGCTAACCTGTCTTTTAACCTGCTTTTAAACCAATATTTATAAACCTTGTTTTT
[2695] AACCAGGGCTGCGCCCTGTGCGCGTGACCGCGCACGCCGAAGGGGGGTGCCCCC
[2696] CCTTCTCGAACCCTCCCGGCCCGCTAACGCGGGCCTCCCATCCCCCCAGGGGCTG CGCCCCTCGGCCGCGAACGGCCTCACCCCAAAAATGGCAGCGCTGGCAGTCCTT
[2697] GCCATTGCCGGGATCGGGGCAGTAACGGGATGGGCGATCAGCCCGACAAGCTAC
[2698] CCCTATTTGTTTATTTTTCTAAATACATTCAAATATGTATCCGCTCATGAGACAAT
[2699] AACCCTGATAAATGCTTCAATAATATTGAAAAAGGAAGAGTATGAGTATTCAAC
[2700] ATTTCCGTGTCGCCCTTATTCCCTTTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTC
[2701] ACCCAGAAACGCTGGTGAAAGTAAAAGATGCTGAAGATCAGTTGGGTGCACGAG
[2702] TGGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTGAGAGTTTTCGCCC
[2703] CGAAGAACGTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTA
[2704] TTATCCCGTATTGACGCCGGGCAAGAGCAACTCGGTCGCCGCATACACTATTCTC
[2705] AGAATGACTTGGTTGAGTACTCACCAGTCACAGAAAAGCATCTTACGGATGGCA
[2706] TGACAGTAAGAGAATTATGCAGTGCTGCCATAACCATGAGTGATAACACTGCGG
[2707] CCAACTTACTTCTGACAACGATCGGAGGACCGAAGGAGCTAACCGCTTTTTTGCA
[2708] CAACATGGGGGATCATGTAACTCGCCTTGATCGTTGGGAACCGGAGCTGAATGA
[2709] AGCCATACCAAACGACGAGCGTGACACCACGATGCCTGTAGCAATGGCAACAAC
[2710] GTTGCGCAAACTATTAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAATTA
[2711] ATAGACTGGATGGAGGCGGATAAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTC
[2712] CGGCTGGCTGGTTTATTGCTGATAAATCTGGAGCCGGTGAGCGTGGGTCTCGCGG
[2713] TATCATTGCAGCACTGGGGCCAGATGGTAAGCCCTCCCGTATCGTAGTTATCTAC
[2714] ACGACGGGGAGTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGAGATA
[2715] GGTGCCTCACTGATTAAGCATTGGTAACTGTCAGACCAAGTTTACTCATATATAC
[2716] TTTAGATTGATTTAAAACTTCATTTTTAATTTAAAAGGATCTAGGTGAAGATCCTT
[2717] TTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGTTCCACTGAGCGTC
[2718] AGACCCCGTAGAAAAGATCAAAGGATCTTCTTGAGATCCTTTTTTTCTGCGCGTA
[2719] ATCTGCTGCTTGCAAACAAAAAAACCACCGCTACCAGCGGTGGTTTGTTTGCCGG
[2720] ATCAAGAGCTACCAACTCTTTTTCCGAAGGTAACTGGCTTCAGCAGAGCGCAGAT
[2721] ACCAAATACTGTCCTTCTAGTGTAGCCGTAGTTAGGCCACCACTTCAAGAACTCT
[2722] GTAGCACCGCCTACATACCTCGCTCTGCTAATCCTGTTACCAGTGGCTGCTGCCA
[2723] GTGGCGATAAGTCGTGTCTTACCGGGTTGGACTCAAGACGATAGTTACCGGATAA
[2724] GGCGCAGCGGTCGGGCTGAACGGGGGGTTCGTGCACACAGCCCAGCTTGGAGCG
[2725] AACGACCTACACCGAACTGAGATACCTACAGCGTGAGCTATGAGAAAGCGCCAC
[2726] GCTTCCCGAAGGGAGAAAGGCGGACAGGTATCCGGTAAGCGGCAGGGTCGGAA
[2727] CAGGAGAGCGCACGAGGGAGCTTCCAGGGGGAAACGCCTGGTATCTTTATAGTC
[2728] CTGTCGGGTTTCGCCACCTCTGACTTGAGCGTCGATTTTTGTGATGCTCGTCAGGG GGGCGGAGCCTATGGAAAAACGCCAGCAACGCGGCCTTTTTACGGTTCCTGGCCT
[2729] TTTGCTGGCCTTTTGCTCACATGGACTCTAGCTAGAGGATCACAGGCAGCAACGC
[2730] TCTGTCATCGTTACAATCAACATGCTACCCTCCGCGAGATCATCCGTGTTTCAAA
[2731] CCCGGCAGCTTAGTTGCCGTTCTTCCGAATAGCATCGGTAACATGAGCAAAGTCT
[2732] GCCGCCTTACAACGGCTCTCCCGCTGACGCCGTCCCGGACTGATGGGCTGCCTGT
[2733] ATCGAGTGGTGATTTTGTGCCGAGCTGCCGGTCGGGGAGCTGTTGGCTGGCTGGT
[2734] GGCAGGATATATTGTGGTGTAAACAAATTGACGCTTAGACAACTTAATAACACAT
[2735] TGCGGACGTTTTTAATGATCGAATACTAACGTCTCTACCAGATATCAGCTTGCAT
[2736] GCCGGTCGATCTAGTAACATAGATGACACCGCGCGCGATAATTTATCCTAGTTTG
[2737] CGCGCTATATTTTGTTTTCTATCGCGTATTAAATGTATAATTGCGGGACTCTAATC
[2738] ATAAAAACCCATCTCATAAATAACGTCATGCATTACATGTTAATTATTACATGCT
[2739] TAACGTAATTCAACAGAAATTATATGATAATCATCGCAAGACCGGCAACAGGAT
[2740] TCAATCTTAAGAAACTTTATTGCCAAATGTTTGAACGATCTGCTTGACTCTAGCTA
[2741] GAGTCCGAACCCCAGAGTCCCGCTCAGAAGAACTCGTCAAGAAGGCGATAGAAG
[2742] GCGATGCGCTGCGAATCGGGAGCGGCGATACCGTAAAGCACGAGGAAGCGGTCA
[2743] GCCCATTCGCCGCCAAGCTCTTCAGCAATATCACGGGTAGCCAACGCTATGTCCT
[2744] GATAGCGGTCCGCCACACCCAGCCGGCCACAGTCGATGAATCCAGAAAAGCGGC
[2745] CATTTTCCACCATGATATTCGGCAAGCAGGCATCGCCGTGGGTCACGACGAGATC
[2746] CTCGCCGTCGGGCATCCGCGCCTTGAGCCTGGCGAACAGTTCGGCTGGCGCGAGC
[2747] CCCTGATGCTCTTCGTCCAGATCATCCTGATCGACAAGACCGGCTTCCATCCGAG
[2748] TACGTGCTCGCTCGATGCGATGTTTCGCTTGGTGGTCGAATGGGCAGGTAGCCGG
[2749] ATCAAGCGTATGCAGCCGCCGCATTGCATCAGCCATGATGGATACTTTCTCGGCA
[2750] GGAGCAAGGTGAGATGACAGGAGATCCTGCCCCGGCACTTCGCCCAATAGCAGC
[2751] CAGTTCCTTCCCGCTTCAGTGACAACGTCGAGCACAGCTGCGCAAGGAACGCCCG
[2752] TTGTGGCCAGCCACGATAGCCGCGCTGCCTCGTCTTGGAGTTCATTCAGGGCACC
[2753] GGACAGGTCGGTCTTGACAAAAAGAACCGGGCGCCCCTGCGCTGACAGCCGGAA
[2754] CACGGCGGCATCAGAGCAGCCGATTGTTTGTTGTGCCCAGTCATAGCCGAATAGC
[2755] CTCTCCACCCAAGCGGCCGGAGAACCTGCGTGCAATCCATCTTGTTCAATCATGC
[2756] CTGCATCGAGTTGAGAGTGAATATGAGACTCTAATTGGATACCGAGGGGAATTT
[2757] ATGGAACGTCAGTGGAGCATTTTTGACAAGAAATATTTGCTAGCTGATAGTGACC
[2758] TTAGGCGACTTTTGAACGCGCAATAATGGTTTCTGACGTATGTGCTTAGCTCATT
[2759] AAACTCCAGAAACCCGCGGCTCAGTGGCTCCTTCAACGTTGCGGTTCTGTCAGTT CCAAACGTAAAACGGCTTGTCCCGCGTCATCGGCGGGGGTCATAACGTGACTCCC
[2760] TTAATTCTCCGCTCATGATCGATATCCATTGAAGAGCAAGCT
[2761] 37. SEQ ID NO: 37 - pRIC3 L1:2C7 DE_i (Generation II)
[2762] GAAGAGCGTGACTCCGAGGGGTTGCCTCAAACTCTATCTTATAACCGGCGTGGA
[2763] GGCATGGAGGCAGGGGTATTTTGGTCATTTTAATAGATAGTGGAAAATGACGTG
[2764] GAATTTACTTAAAGACGAAGTCTTTGCGACAAGGGGGGGCCCACGCCGAATTTA
[2765] ATATTACCGGCGTGGCCCCCCCTTATCGCGAGTGCTTTAGCACGAGCGGTCCAGA
[2766] TTTAAAGTAGAAAATTTCCCGCCCACTAGGGTTAAAGGTGTTCACACTATAAAAG
[2767] CATATACGATGTGATGGTATTTGCTCGACCTGGTCCAAAGACCAGAGGGCTATTG
[2768] AGACTTTTCAACAAAGGGTAATATCGGGAAACCTCCTCGGATTCCATTGCCCAGC
[2769] TATCTGTCACTTCATCGAAAGGACAGTAGAAAAGGAAGATGGCTTCTACAAATG
[2770] CCATCATTGCGATAAAGGAAAGGCTATCGTTCAAGATGCCTCTACCGACAGTGGT
[2771] CCCAAAGATGGACCCCCACCCACGAGGAACATCGTGGAAAAAGAAGACGTTCCA
[2772] ACCACGTCTTCAAAGCAAGTGGATTGATGTGATACATGGTGGAGCACGACACTCT
[2773] CGTCTACTCCAAGAATATCAAAGATACAGTCTCAGAAGACCAGAGGGCTATTGA
[2774] GACTTTTCAACAAAGGGTAATATCGGGAAACCTCCTCGGATTCCATTGCCCAGCT
[2775] ATCTGTCACTTCATCGAAAGGACAGTAGAAAAGGAAGATGGCTTCTACAAATGC
[2776] CATCATTGCGATAAAGGAAAGGCTATCGTTCAAGATGCCTCTACCGACAGTGGTC
[2777] CCAAAGATGGACCCCCACCCACGAGGAACATCGTGGAAAAAGAAGACGTTCCAA
[2778] CCACGTCTTCAAAGCAAGTGGATTGATGTGATATCTCCACTGACGTAAGGGATGA
[2779] CGCACAATCCCACTATCCTTCGCAAGACCCTTCCTCTATATAAGGAAGTTCATTTC
[2780] ATTTGGAGAGGACACGCTGAGTTCACAACACAAATCAGATTTATAGAGAGATTT
[2781] ATAAAAAAAAAAAAACATGAGCCTGTGGCTGCCTAGCGAGGCAACCGTGTACCT
[2782] GCCACCTGTGCCAGTGAGCAAGGTGGTGTCCACCGACGAGTATGTGGCCCGGAC
[2783] AAACATCTACTATCACGCAGGCACATCCAGACTGCTGGCAGTGGGCCACCCCTAC
[2784] TTCCCTATCAAGAAGCCCAACAATAACAAGATCCTGGTGCCTAAGGTGTCCGGCC
[2785] TGCAGTATAGGGTGTTCCGCATCCACCTGCCAGATCCCAACAAGTTCGGCTTTCC
[2786] TGACACCTCTTTTTACAATCCAGATACACAGAGGCTGGTGTGGGCATGCGTGGGA
[2787] GTGGAAGTGGGAAGGGGCCAGCCTCTGGGAGTGGGAATCTCCGGACACCCACTG
[2788] CTGAATAAGCTGGACGATACCGAGAACATCCCAGTGCTGGACGAGAATGGACTG
[2789] TTTGCACCAGCATCTGCCTACGCAGCAAATGCAGGAGTGGACAACAGGGAGTGT
[2790] ATCAGCATGGATTATAAGCAGACCCAGCTGTGCCTGATCGGCTGTAAGCCACCA ATCGGAGAGCACTGGGGCAAGGGCTCTCCATGCACAAATGTGGCCGTGAACCCC
[2791] GGCGATTGTCCTCCACTGGAGCTGATCAACACCGTGATCCAGGACGGCGATATG
[2792] GTGGACACAGGCTTCGGCGCCATGGACTTCACCACCCTGCAGGCCAATAAGAGC
[2793] GAGGTGCCTCTGGACATCTGCACCTCCATCTGTAAGTACCCCGATTATATCAAGA
[2794] TGGTGTCCGAGCCTTACGGCGACTCTCTGTTCTTTTATCTGCGGAGAGAGCAGAT
[2795] GTTCGTGAGGCACCTGTTTAACAGGGCAGGAGCAGTGGGAGAGAATGTGCCAGA
[2796] CGATCTGTACATCAAGGGCTCCGGCTCTACCGCCAATCTGGCCAGCTCCAACTAT
[2797] TTCCCTACCCCAAGCGGCTCCATGGTGACAAGCGACGCCCAGATCTTTAACAAGC
[2798] CATACTGGCTGCAGAGGGCACAGGGACACAATAACGGCATCTGCTGGGGCAACC
[2799] AGCTGTTCGTGACCGTGGTGGATACCACACGCTCTACAAATATGAGCCTGTGCGC
[2800] CGCCATCTCTACCAGCGAGACCACATACAAGAACACAAACTTTAAGGAGTACCT
[2801] GCGGCACGGCGAGGAGTATGACCTGCAGTTCATCTTTCAGCTGTGCAAGATCACC
[2802] CTGACAGCCGATGTGATGACCTACATCCACTCCATGAACTCTACAATCCTGGAGG
[2803] ACTGGAATTTCGGACTGCAGCCACCTCCAGGAGGCACCCTGGAGGATACATATA
[2804] GGTTTGTGACCTCTCAGGCCATCGCCTGTCAGAAGCACACACCCCCTGCCCCAAA
[2805] GGAGGACCCCCTGAAGAAGTACACCTTCTGGGAAGTGAATCTGAAGGAGAAGTT
[2806] TAGCGCCGACCTGGATCAGTTCCCACTGGGACGGAAGTTTCTGCTGCAGGCAGGC
[2807] CTGAAGGCAAAGCCAAAGTTCACCCTGGGCAAGAGAAAGGCCACCCCTACCACA
[2808] TCTAGCACATCCACCACAGCCAAGCGGAAGAAGAGAAAGCTGTGAGGATCCCTC
[2809] GAGCTCTCTAGAGTCCGCAAAAATCACCAGTCTCTCTCTACAAATCTATCTCTCTC
[2810] TATTTTTCTCCAGAATAATGTGTGAGTAGTTCCCAGATAAGGGAATTAGGGTTCT
[2811] TATAGGGTTTCGCTCATGTGTTGAGCATATAAGAAACCCTTAGTATGTATTTGTAT
[2812] TTGTAAAATACTTCTATCAATAAAATTTCTAATTCCTAAAACCAAAATCCAGTGA
[2813] CCGGGCGGCGGGTCGAGAATGATTATTTTATGAATATATTTCATTGTGCAAGTAG
[2814] ATAGAAATTACATATGTTACATAACACACGAAATAAACAAAAAAAGACAATCCA
[2815] AAAACAAACACCCCAAAAAAAATAATCACTTTAGATAAACTCGTATGAGGAGAG
[2816] GCACGTTCAGTGACTCGACGATTCCCGAGCAAAAAAAGTCTCCCCGTCACACATA
[2817] TAGTGGGTGACGCAATTATCTTTAAAGTAATCCTTCTGTTGACTTGTCATTGATAA
[2818] CATCCAGTCTTCGTCAGGATTGCAAAGAATTATAGAAGGGATCCCACCTTTTATT
[2819] TTCTTCTTTTTTCCATATTTAGGGTTGACAGTGAAATCAGACTGGCAACCTATTAA
[2820] TTGCTTCCACAATGGGACGAACTTGAAGGGGATGTCGTCGATGATATTATAGGTG
[2821] GCGTGTTCATCGTAGTTGGTGAAATCGATGGTACCGTTCCAATAGTTGTGTCGTC
[2822] CGAGACTTCTAGCCCAGGTGGTCTTTCCGGTACGAGTTGGTCCGCAGATGTAGAG GCTGGGGTGTCGGATTCCATTCCTTCCATTGTCCTGGTTAAATCGGCCATCCATTC
[2823] AAGGTCAGATTGAGCTTGTTGGTATGAGACAGGATGTATGTAAGTATAAGCGTCT
[2824] ATGCTTACATGGTATAGATGGGTTTCCCTCCAGGAGTGTAGATCTTCGTGGCAGC
[2825] GAAGATCTGATTCTGTGAAGGGCGACACATACGGTTCAGGTTGTGGAGGGAATA
[2826] ATTTGTTGGCTGAATATTCCAGCCATTGAAGTTTTGTTGCCCATTCATGAGGGAAT
[2827] TCTTCCTTGATCATGTCAAGATATTCCTCCTTAGACGTTGCAGTCTGGATAATAGT
[2828] TCTCCATCGTGCGTCAGATTTGCGAGGAGAGACCTTATGATCTCGGAAATCTCCT
[2829] CTGGTTTTAATATCTCCGTCCTTTGATATGTAATCAAGGACTTGTTTAGAGTTTCT
[2830] AGCTGGCTGGATATTAGGGTGATTTCCTTCAAAATCGAAAAAAGAAGGATCCCT
[2831] AATACAAGGTTTTTTATCAAGCTGGAGAAGAGCATGATAGTGGGTAGTGCCATCT
[2832] TGATGAAGCTCAGAAGCAACACCAAGGAAGAAAATAAGAAAAGGTGTGAGTTTC
[2833] TCCCAGAGAAACTGGAATAAATCATCTCTTTGAGATGAGCACTTGGGATAGGTA
[2834] AGGAAAACATATTTAGATTGGAGTCTGAAGTTCTTACTAGCAGAAGGCATGTTGT
[2835] TGTGACTCCGAGGGGTTGCCTCAAACTCTATCTTATAACCGGCGTGGAGGCATGG
[2836] AGGCAGGGGTATTTTGGTCATTTTAATAGATAGTGGAAAATGACGTGGAATTTAC
[2837] TTAAAGACGAAGTCTTTGCGACAAGGGGGGGCCCACGCCGAATTTAATATTACC
[2838] GGCGTGGCCCCCCCTTATCGCGAGTGCTTTAGCACGAGCGGTCCAGATTTAAAGT
[2839] AGAAAATTTCCCGCCCACTAGGGTTAAAGGTGTTCACACTATACAAGCATATACG
[2840] ATGTGATGGTATTGACTAGAGTTTAAACTATCAGTGTTTGACAGGATATATTGGC
[2841] GGGTAAACCTAAGAGAAAAGAGCGTTTATTAGAATAATCGGATATTTAAAAGGG
[2842] CGTGAAAAGGTTTATCCGTTCGTCCATTTGTATGTGTACATCACCGACGAGCAAG
[2843] GCAAGACCGAGCGCCTTTCCGACGCTCACCGGGCTGGTTGCCCTCGCCGCTGGGC
[2844] TGGCGGCCGTCTATGGCCCTGCAAACGCGCCAGAAACGCCGTCGAAGCCGTGTG
[2845] CGAGACACCGGCCGCCGGCGTTGTGGATACCTCGCGGAAAACTTGGCCCTCACT
[2846] GACAGATGAGGGGCGGACGTTGACACTTGAGGGGCCGACTCACCCGGCGCGGCG
[2847] TTGACAGATGAGGGGCAGGCTCGATTTCGGCCGGCGACGTGGAGCTGGCCAGCC
[2848] TCGCAAATCGGCGAAAACGCCTGATTTTACGCGAGTTTCCCACAGATGATGTGGA
[2849] CAAGCCTGGGGATAAGTGCCCTGCGGTATTGACACTTGAGGGGCGCGACTACTG
[2850] ACAGATGAGGGGCGCGATCCTTGACACTTGAGGGGCAGAGTGCTGACAGATGAG
[2851] GGGCGCACCTATTGACATTTGAGGGGCTGTCCACAGGCAGAAAATCCAGCATTT
[2852] GCAAGGGTTTCCGCCCGTTTTTCGGCCACCGCTAACCTGTCTTTTAACCTGCTTTT
[2853] AAACCAATATTTATAAACCTTGTTTTTAACCAGGGCTGCGCCCTGTGCGCGTGAC
[2854] CGCGCACGCCGAAGGGGGGTGCCCCCCCTTCTCGAACCCTCCCGGCCCGCTAACG CGGGCCTCCCATCCCCCCAGGGGCTGCGCCCCTCGGCCGCGAACGGCCTCACCCC
[2855] AAAAATGGCAGCGCTGGCAGTCCTTGCCATTGCCGGGATCGGGGCAGTAACGGG
[2856] ATGGGCGATCAGCCCGAAAGCTACCCCTATTTGTTTATTTTTCTAAATACATTCAA
[2857] ATATGTATCCGCTCATGAGACAATAACCCTGATAAATGCTTCAATAATATTGAAA
[2858] AAGGAAGAGTATGAGTATTCAACATTTCCGTGTCGCCCTTATTCCCTTTTTTGCGG
[2859] CATTTTGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTAAAAGATGC
[2860] TGAAGATCAGTTGGGTGCACGAGTGGGTTACATCGAACTGGATCTCAACAGCGG
[2861] TAAGATCCTTGAGAGTTTTCGCCCCGAAGAACGTTTTCCAATGATGAGCACTTTT
[2862] AAAGTTCTGCTATGTGGCGCGGTATTATCCCGTATTGACGCCGGGCAAGAGCAAC
[2863] TCGGTCGCCGCATACACTATTCTCAGAATGACTTGGTTGAGTACTCACCAGTCAC
[2864] AGAAAAGCATCTTACGGATGGCATGACAGTAAGAGAATTATGCAGTGCTGCCAT
[2865] AACCATGAGTGATAACACTGCGGCCAACTTACTTCTGACAACGATCGGAGGACC
[2866] GAAGGAGCTAACCGCTTTTTTGCACAACATGGGGGATCATGTAACTCGCCTTGAT
[2867] CGTTGGGAACCGGAGCTGAATGAAGCCATACCAAACGACGAGCGTGACACCACG
[2868] ATGCCTGTAGCAATGGCAACAACGTTGCGCAAACTATTAACTGGCGAACTACTTA
[2869] CTCTAGCTTCCCGGCAACAATTAATAGACTGGATGGAGGCGGATAAAGTTGCAG
[2870] GACCACTTCTGCGCTCGGCCCTTCCGGCTGGCTGGTTTATTGCTGATAAATCTGG
[2871] AGCCGGTGAGCGTGGGTCTCGCGGTATCATTGCAGCACTGGGGCCAGATGGTAA
[2872] GCCCTCCCGTATCGTAGTTATCTACACGACGGGGAGTCAGGCAACTATGGATGAA
[2873] CGAAATAGACAGATCGCTGAGATAGGTGCCTCACTGATTAAGCATTGGTAACTGT
[2874] CAGACCAAGTTTACTCATATATACTTTAGATTGATTTAAAACTTCATTTTTAATTT
[2875] AAAAGGATCTAGGTGAAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTAAC
[2876] GTGAGTTTTCGTTCCACTGAGCGTCAGACCCCGTAGAAAAGATCAAAGGATCTTC
[2877] TTGAGATCCTTTTTTTCTGCGCGTAATCTGCTGCTTGCAAACAAAAAAACCACCG
[2878] CTACCAGCGGTGGTTTGTTTGCCGGATCAAGAGCTACCAACTCTTTTTCCGAAGG
[2879] TAACTGGCTTCAGCAGAGCGCAGATACCAAATACTGTTCTTCTAGTGTAGCCGTA
[2880] GTTAGGCCACCACTTCAAGAACTCTGTAGCACCGCCTACATACCTCGCTCTGCTA
[2881] ATCCTGTTACCAGTGGCTGCTGCCAGTGGCGATAAGTCGTGTCTTACCGGGTTGG
[2882] ACTCAAGACGATAGTTACCGGATAAGGCGCAGCGGTCGGGCTGAACGGGGGGTT
[2883] CGTGCACACAGCCCAGCTTGGAGCGAACGACCTACACCGAACTGAGATACCTAC
[2884] AGCGTGAGCTATGAGAAAGCGCCACGCTTCCCGAAGGGAGAAAGGCGGACAGG
[2885] TATCCGGTAAGCGGCAGGGTCGGAACAGGAGAGCGCACGAGGGAGCTTCCAGG
[2886] GGGAAACGCCTGGTATCTTTATAGTCCTGTCGGGTTTCGCCACCTCTGACTTGAG CGTCGATTTTTGTGATGCTCGTCAGGGGGGCGGAGCCTATGGAAAAACGCCAGC
[2887] AACGCGGCCTTTTTACGGTTCCTGGCCTTTTGCTGGCCTTTTGCTCACATGGACTC
[2888] TAGCTAGAGGATCACAGGCAGCAACGCTCTGTCATCGTTACAATCAACATGCTAC
[2889] CCTCCGCGAGATCATCCGTGTTTCAAACCCGGCAGCTTAGTTGCCGTTCTTCCGA
[2890] ATAGCATCGGTAACATGAGCAAAGTCTGCCGCCTTACAACGGCTCTCCCGCTGAC
[2891] GCCGTCCCGGACTGATGGGCTGCCTGTATCGAGTGGTGATTTTGTGCCGAGCTGC
[2892] CGGTCGGGGAGCTGTTGGCTGGCTGGTGGCAGGATATATTGTGGTGTAAACAAA
[2893] TTGACGCTTAGACAACTTAATAACACATTGCGGACGTTTTTAATGATCGAATACT
[2894] AACGTCTCTACCACATT
[2895] 38. SEQ ID NO: 38 - pRIC3 L1:2C7 DE_s (Generation II)
[2896] GAAGAGCGTGACTCCGAGGGGTTGCCTCAAACTCTATCTTATAACCGGCGTGGA
[2897] GGCATGGAGGCAGGGGTATTTTGGTCATTTTAATAGATAGTGGAAAATGACGTG
[2898] GAATTTACTTAAAGACGAAGTCTTTGCGACAAGGGGGGGCCCACGCCGAATTTA
[2899] ATATTACCGGCGTGGCCCCCCCTTATCGCGAGTGCTTTAGCACGAGCGGTCCAGA
[2900] TTTAAAGTAGAAAATTTCCCGCCCACTAGGGTTAAAGGTGTTCACACTATAAAAG
[2901] CATATACGATGTGATGGTATTTGCTCGACCTGGTCCAAAGACCAGAGGGCTATTG
[2902] AGACTTTTCAACAAAGGGTAATATCGGGAAACCTCCTCGGATTCCATTGCCCAGC
[2903] TATCTGTCACTTCATCGAAAGGACAGTAGAAAAGGAAGATGGCTTCTACAAATG
[2904] CCATCATTGCGATAAAGGAAAGGCTATCGTTCAAGATGCCTCTACCGACAGTGGT
[2905] CCCAAAGATGGACCCCCACCCACGAGGAACATCGTGGAAAAAGAAGACGTTCCA
[2906] ACCACGTCTTCAAAGCAAGTGGATTGATGTGATACATGGTGGAGCACGACACTCT
[2907] CGTCTACTCCAAGAATATCAAAGATACAGTCTCAGAAGACCAGAGGGCTATTGA
[2908] GACTTTTCAACAAAGGGTAATATCGGGAAACCTCCTCGGATTCCATTGCCCAGCT
[2909] ATCTGTCACTTCATCGAAAGGACAGTAGAAAAGGAAGATGGCTTCTACAAATGC
[2910] CATCATTGCGATAAAGGAAAGGCTATCGTTCAAGATGCCTCTACCGACAGTGGTC
[2911] CCAAAGATGGACCCCCACCCACGAGGAACATCGTGGAAAAAGAAGACGTTCCAA
[2912] CCACGTCTTCAAAGCAAGTGGATTGATGTGATATCTCCACTGACGTAAGGGATGA
[2913] CGCACAATCCCACTATCCTTCGCAAGACCCTTCCTCTATATAAGGAAGTTCATTTC
[2914] ATTTGGAGAGGACACGCTGAGTTCACAACACAAATCAGATTTATAGAGAGATTT
[2915] ATAAAAAAAAAAAAACATGAGCCTGTGGCTGCCTTCCGAGGCAACCGTGTACCT
[2916] GCCACCTGTGCCAGTGAGCAAGGTGGTGTCCACCGACGAGTATGTGGCCCGGAC
[2917] AAACATCTACTATCACGCCGGCACATCTAGACTGCTGGCCGTGGGCCACCCCTAC TTCCCTATCAAGAAGCCCAACAATAACAAGATCCTGGTGCCTAAGGTGTCTGGCC
[2918] TGCAGTATAGGGTGTTCCGCATCCACCTGCCAGATCCCAATAAGTTCGGCTTTCC
[2919] TGACACCAGCTTTTACAACCCAGATACACAGAGGCTGGTGTGGGCATGCGTGGG
[2920] AGTGGAAGTGGGAAGGGGCCAGCCTCTGGGAGTGGGAATCTCTGGACACCCACT
[2921] GCTGAATAAGCTGGACGATACCGAGATCCCAGTGCTGGACGAGAACGGCCTGTT
[2922] TGCCCCCATGGATTATAAGCAGACACAGCTGTGCCTGATCGGCTGTAAGCCACCA
[2923] ATCGGAGAGCACTGGGGCAAGGGATCCCCATGCACCAATGTGGCCGTGAACCCC
[2924] GGCGACTGTCCTCCACTGGAGCTGATCAATACCGTGATCCAGGACGGCGATATG
[2925] GTGGACACAGGCTTCGGCGCCATGGACTTCACCACCCTGCAGGCCAACAAGAGC
[2926] GAGGTGCCTCTGGACATCTGCACCTCCATCTGTAAGTACCCCGATTATATCAAGA
[2927] TGGTGTCCGAGCCTTACGGCGATTCTCTGTTCTTTTATCTGCGGAGAGAGCAGAT
[2928] GTTCGTGAGGCACCTGTTTAATAGGGCAGGAGCAGTGGGAGAGAACGTGCCAGA
[2929] CGATCTGTACATCAAGGGCTCCGGCTCTACCGCCAATCTGGCCAGCTCCAACTAT
[2930] TTCCCTACCCCAAGCGGCTCCATGGTGACAAGCGACGCCCAGATCTTTAATAAGC
[2931] CATACTGGCTGCAGAGGGCACAGGGACACAATAACGGCATCTGCTGGGGCAATC
[2932] AGCTGTTCGTGACCGTGGTGGATACCACACGCTCTACAAACATGAGCCTGTGCGC
[2933] CGCCATCTCTACCAGCGAGACCACATACAAGAACACAAACTTTAAGGAGTACCT
[2934] GCGGCACGGCGAGGAGTATGACCTGCAGTTCATCTTTCAGCTGTGCAAGATCACC
[2935] CTGACAGCCGATGTGATGACCTACATCCACTCCATGAACAGCACAATCCTGGAG
[2936] GACTGGAACTTCGGACTGCAGCCACCTCCAGGAGGCACCCTGGAGGATACATAT
[2937] AGGTTTGTGACCAGCCAGGCCATCGCCTGTCAGAAGCACACACCCCCTGCCCCAA
[2938] AGGAGGACCCCCTGAAGAAGTACACCTTCTGGGAGGTGAACCTGAAGGAGAAGT
[2939] TTTCCGCCGACCTGGATCAGTTCCCACTGGGACGGAAGTTTCTGCTGCAGGCAGG
[2940] CCTGAAGGCAAAGCCAAAGTTCACCCTGGGCAAGAGAAAGGCCACCCCTACCAC
[2941] ATCTAGCACATCCACCACAGCCAAGCGGAAGAAGAGAAAGCTGTGAGGATCCCT
[2942] CGAGCTCTCTAGAGTCCGCAAAAATCACCAGTCTCTCTCTACAAATCTATCTCTCT
[2943] CTATTTTTCTCCAGAATAATGTGTGAGTAGTTCCCAGATAAGGGAATTAGGGTTC
[2944] TTATAGGGTTTCGCTCATGTGTTGAGCATATAAGAAACCCTTAGTATGTATTTGTA
[2945] TTTGTAAAATACTTCTATCAATAAAATTTCTAATTCCTAAAACCAAAATCCAGTG
[2946] ACCGGGCGGCGGGTCGAGAATGATTATTTTATGAATATATTTCATTGTGCAAGTA
[2947] GATAGAAATTACATATGTTACATAACACACGAAATAAACAAAAAAAGACAATCC
[2948] AAAAACAAACACCCCAAAAAAAATAATCACTTTAGATAAACTCGTATGAGGAGA
[2949] GGCACGTTCAGTGACTCGACGATTCCCGAGCAAAAAAAGTCTCCCCGTCACACAT ATAGTGGGTGACGCAATTATCTTTAAAGTAATCCTTCTGTTGACTTGTCATTGATA
[2950] ACATCCAGTCTTCGTCAGGATTGCAAAGAATTATAGAAGGGATCCCACCTTTTAT
[2951] TTTCTTCTTTTTTCCATATTTAGGGTTGACAGTGAAATCAGACTGGCAACCTATTA
[2952] ATTGCTTCCACAATGGGACGAACTTGAAGGGGATGTCGTCGATGATATTATAGGT
[2953] GGCGTGTTCATCGTAGTTGGTGAAATCGATGGTACCGTTCCAATAGTTGTGTCGT
[2954] CCGAGACTTCTAGCCCAGGTGGTCTTTCCGGTACGAGTTGGTCCGCAGATGTAGA
[2955] GGCTGGGGTGTCGGATTCCATTCCTTCCATTGTCCTGGTTAAATCGGCCATCCATT
[2956] CAAGGTCAGATTGAGCTTGTTGGTATGAGACAGGATGTATGTAAGTATAAGCGTC
[2957] TATGCTTACATGGTATAGATGGGTTTCCCTCCAGGAGTGTAGATCTTCGTGGCAG
[2958] CGAAGATCTGATTCTGTGAAGGGCGACACATACGGTTCAGGTTGTGGAGGGAAT
[2959] AATTTGTTGGCTGAATATTCCAGCCATTGAAGTTTTGTTGCCCATTCATGAGGGA
[2960] ATTCTTCCTTGATCATGTCAAGATATTCCTCCTTAGACGTTGCAGTCTGGATAATA
[2961] GTTCTCCATCGTGCGTCAGATTTGCGAGGAGAGACCTTATGATCTCGGAAATCTC
[2962] CTCTGGTTTTAATATCTCCGTCCTTTGATATGTAATCAAGGACTTGTTTAGAGTTT
[2963] CTAGCTGGCTGGATATTAGGGTGATTTCCTTCAAAATCGAAAAAAGAAGGATCCC
[2964] TAATACAAGGTTTTTTATCAAGCTGGAGAAGAGCATGATAGTGGGTAGTGCCATC
[2965] TTGATGAAGCTCAGAAGCAACACCAAGGAAGAAAATAAGAAAAGGTGTGAGTTT
[2966] CTCCCAGAGAAACTGGAATAAATCATCTCTTTGAGATGAGCACTTGGGATAGGTA
[2967] AGGAAAACATATTTAGATTGGAGTCTGAAGTTCTTACTAGCAGAAGGCATGTTGT
[2968] TGTGACTCCGAGGGGTTGCCTCAAACTCTATCTTATAACCGGCGTGGAGGCATGG
[2969] AGGCAGGGGTATTTTGGTCATTTTAATAGATAGTGGAAAATGACGTGGAATTTAC
[2970] TTAAAGACGAAGTCTTTGCGACAAGGGGGGGCCCACGCCGAATTTAATATTACC
[2971] GGCGTGGCCCCCCCTTATCGCGAGTGCTTTAGCACGAGCGGTCCAGATTTAAAGT
[2972] AGAAAATTTCCCGCCCACTAGGGTTAAAGGTGTTCACACTATACAAGCATATACG
[2973] ATGTGATGGTATTGACTAGAGTTTAAACTATCAGTGTTTGACAGGATATATTGGC
[2974] GGGTAAACCTAAGAGAAAAGAGCGTTTATTAGAATAATCGGATATTTAAAAGGG
[2975] CGTGAAAAGGTTTATCCGTTCGTCCATTTGTATGTGTACATCACCGACGAGCAAG
[2976] GCAAGACCGAGCGCCTTTCCGACGCTCACCGGGCTGGTTGCCCTCGCCGCTGGGC
[2977] TGGCGGCCGTCTATGGCCCTGCAAACGCGCCAGAAACGCCGTCGAAGCCGTGTG
[2978] CGAGACACCGGCCGCCGGCGTTGTGGATACCTCGCGGAAAACTTGGCCCTCACT
[2979] GACAGATGAGGGGCGGACGTTGACACTTGAGGGGCCGACTCACCCGGCGCGGCG
[2980] TTGACAGATGAGGGGCAGGCTCGATTTCGGCCGGCGACGTGGAGCTGGCCAGCC
[2981] TCGCAAATCGGCGAAAACGCCTGATTTTACGCGAGTTTCCCACAGATGATGTGGA CAAGCCTGGGGATAAGTGCCCTGCGGTATTGACACTTGAGGGGCGCGACTACTG
[2982] ACAGATGAGGGGCGCGATCCTTGACACTTGAGGGGCAGAGTGCTGACAGATGAG
[2983] GGGCGCACCTATTGACATTTGAGGGGCTGTCCACAGGCAGAAAATCCAGCATTT
[2984] GCAAGGGTTTCCGCCCGTTTTTCGGCCACCGCTAACCTGTCTTTTAACCTGCTTTT
[2985] AAACCAATATTTATAAACCTTGTTTTTAACCAGGGCTGCGCCCTGTGCGCGTGAC
[2986] CGCGCACGCCGAAGGGGGGTGCCCCCCCTTCTCGAACCCTCCCGGCCCGCTAACG
[2987] CGGGCCTCCCATCCCCCCAGGGGCTGCGCCCCTCGGCCGCGAACGGCCTCACCCC
[2988] AAAAATGGCAGCGCTGGCAGTCCTTGCCATTGCCGGGATCGGGGCAGTAACGGG
[2989] ATGGGCGATCAGCCCGAAAGCTACCCCTATTTGTTTATTTTTCTAAATACATTCAA
[2990] ATATGTATCCGCTCATGAGACAATAACCCTGATAAATGCTTCAATAATATTGAAA
[2991] AAGGAAGAGTATGAGTATTCAACATTTCCGTGTCGCCCTTATTCCCTTTTTTGCGG
[2992] CATTTTGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTAAAAGATGC
[2993] TGAAGATCAGTTGGGTGCACGAGTGGGTTACATCGAACTGGATCTCAACAGCGG
[2994] TAAGATCCTTGAGAGTTTTCGCCCCGAAGAACGTTTTCCAATGATGAGCACTTTT
[2995] AAAGTTCTGCTATGTGGCGCGGTATTATCCCGTATTGACGCCGGGCAAGAGCAAC
[2996] TCGGTCGCCGCATACACTATTCTCAGAATGACTTGGTTGAGTACTCACCAGTCAC
[2997] AGAAAAGCATCTTACGGATGGCATGACAGTAAGAGAATTATGCAGTGCTGCCAT
[2998] AACCATGAGTGATAACACTGCGGCCAACTTACTTCTGACAACGATCGGAGGACC
[2999] GAAGGAGCTAACCGCTTTTTTGCACAACATGGGGGATCATGTAACTCGCCTTGAT
[3000] CGTTGGGAACCGGAGCTGAATGAAGCCATACCAAACGACGAGCGTGACACCACG
[3001] ATGCCTGTAGCAATGGCAACAACGTTGCGCAAACTATTAACTGGCGAACTACTTA
[3002] CTCTAGCTTCCCGGCAACAATTAATAGACTGGATGGAGGCGGATAAAGTTGCAG
[3003] GACCACTTCTGCGCTCGGCCCTTCCGGCTGGCTGGTTTATTGCTGATAAATCTGG
[3004] AGCCGGTGAGCGTGGGTCTCGCGGTATCATTGCAGCACTGGGGCCAGATGGTAA
[3005] GCCCTCCCGTATCGTAGTTATCTACACGACGGGGAGTCAGGCAACTATGGATGAA
[3006] CGAAATAGACAGATCGCTGAGATAGGTGCCTCACTGATTAAGCATTGGTAACTGT
[3007] CAGACCAAGTTTACTCATATATACTTTAGATTGATTTAAAACTTCATTTTTAATTT
[3008] AAAAGGATCTAGGTGAAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTAAC
[3009] GTGAGTTTTCGTTCCACTGAGCGTCAGACCCCGTAGAAAAGATCAAAGGATCTTC
[3010] TTGAGATCCTTTTTTTCTGCGCGTAATCTGCTGCTTGCAAACAAAAAAACCACCG
[3011] CTACCAGCGGTGGTTTGTTTGCCGGATCAAGAGCTACCAACTCTTTTTCCGAAGG
[3012] TAACTGGCTTCAGCAGAGCGCAGATACCAAATACTGTTCTTCTAGTGTAGCCGTA
[3013] GTTAGGCCACCACTTCAAGAACTCTGTAGCACCGCCTACATACCTCGCTCTGCTA ATCCTGTTACCAGTGGCTGCTGCCAGTGGCGATAAGTCGTGTCTTACCGGGTTGG
[3014] ACTCAAGACGATAGTTACCGGATAAGGCGCAGCGGTCGGGCTGAACGGGGGGTT
[3015] CGTGCACACAGCCCAGCTTGGAGCGAACGACCTACACCGAACTGAGATACCTAC
[3016] AGCGTGAGCTATGAGAAAGCGCCACGCTTCCCGAAGGGAGAAAGGCGGACAGG
[3017] TATCCGGTAAGCGGCAGGGTCGGAACAGGAGAGCGCACGAGGGAGCTTCCAGG
[3018] GGGAAACGCCTGGTATCTTTATAGTCCTGTCGGGTTTCGCCACCTCTGACTTGAG
[3019] CGTCGATTTTTGTGATGCTCGTCAGGGGGGCGGAGCCTATGGAAAAACGCCAGC
[3020] AACGCGGCCTTTTTACGGTTCCTGGCCTTTTGCTGGCCTTTTGCTCACATGGACTC
[3021] TAGCTAGAGGATCACAGGCAGCAACGCTCTGTCATCGTTACAATCAACATGCTAC
[3022] CCTCCGCGAGATCATCCGTGTTTCAAACCCGGCAGCTTAGTTGCCGTTCTTCCGA
[3023] ATAGCATCGGTAACATGAGCAAAGTCTGCCGCCTTACAACGGCTCTCCCGCTGAC
[3024] GCCGTCCCGGACTGATGGGCTGCCTGTATCGAGTGGTGATTTTGTGCCGAGCTGC
[3025] CGGTCGGGGAGCTGTTGGCTGGCTGGTGGCAGGATATATTGTGGTGTAAACAAA
[3026] TTGACGCTTAGACAACTTAATAACACATTGCGGACGTTTTTAATGATCGAATACT
[3027] AACGTCTCTACCACATT
[3028] 39. SEQ ID NO: 39 - pRIC3 L1:2C7 h4_i (Generation II)
[3029] GAAGAGCGTGACTCCGAGGGGTTGCCTCAAACTCTATCTTATAACCGGCGTGGA
[3030] GGCATGGAGGCAGGGGTATTTTGGTCATTTTAATAGATAGTGGAAAATGACGTG
[3031] GAATTTACTTAAAGACGAAGTCTTTGCGACAAGGGGGGGCCCACGCCGAATTTA
[3032] ATATTACCGGCGTGGCCCCCCCTTATCGCGAGTGCTTTAGCACGAGCGGTCCAGA
[3033] TTTAAAGTAGAAAATTTCCCGCCCACTAGGGTTAAAGGTGTTCACACTATAAAAG
[3034] CATATACGATGTGATGGTATTTGCTCGACCTGGTCCAAAGACCAGAGGGCTATTG
[3035] AGACTTTTCAACAAAGGGTAATATCGGGAAACCTCCTCGGATTCCATTGCCCAGC
[3036] TATCTGTCACTTCATCGAAAGGACAGTAGAAAAGGAAGATGGCTTCTACAAATG
[3037] CCATCATTGCGATAAAGGAAAGGCTATCGTTCAAGATGCCTCTACCGACAGTGGT
[3038] CCCAAAGATGGACCCCCACCCACGAGGAACATCGTGGAAAAAGAAGACGTTCCA
[3039] ACCACGTCTTCAAAGCAAGTGGATTGATGTGATACATGGTGGAGCACGACACTCT
[3040] CGTCTACTCCAAGAATATCAAAGATACAGTCTCAGAAGACCAGAGGGCTATTGA
[3041] GACTTTTCAACAAAGGGTAATATCGGGAAACCTCCTCGGATTCCATTGCCCAGCT
[3042] ATCTGTCACTTCATCGAAAGGACAGTAGAAAAGGAAGATGGCTTCTACAAATGC
[3043] CATCATTGCGATAAAGGAAAGGCTATCGTTCAAGATGCCTCTACCGACAGTGGTC
[3044] CCAAAGATGGACCCCCACCCACGAGGAACATCGTGGAAAAAGAAGACGTTCCAA CCACGTCTTCAAAGCAAGTGGATTGATGTGATATCTCCACTGACGTAAGGGATGA
[3045] CGCACAATCCCACTATCCTTCGCAAGACCCTTCCTCTATATAAGGAAGTTCATTTC
[3046] ATTTGGAGAGGACACGCTGAGTTCACAACACAAATCAGATTTATAGAGAGATTT
[3047] ATAAAAAAAAAAAAACATGAGCCTGTGGCTGCCTTCCGAGGCAACCGTGTACCT
[3048] GCCACCTGTGCCAGTGAGCAAGGTGGTGTCCACCGATGAGTATGTGGCCCGGAC
[3049] AAATATCTACTATCACGCCGGCACATCTAGACTGCTGGCCGTGGGCCACCCCTAC
[3050] TTCCCTATCAAGAAGCCCAACAATAACAAGATCCTGGTGCCTAAGGTGTCTGGCC
[3051] TGCAGTATAGGGTGTTCCGCATCCACCTGCCAGACCCCAATAAGTTCGGCTTTCC
[3052] TGACACCAGCTTTTACAACCCAGATACACAGAGGCTGGTGTGGGCATGCGTGGG
[3053] AGTGGAAGTGGGAAGGGGCCAGCCTCTGGGAGTGGGAATCTCTGGACACCCACT
[3054] GCTGAATAAGCTGGACGATACCGAGAACGCCAGCGCCTACGCAGCAAATGCAGG
[3055] AGTGGACAACAGGGAGTGTATCTCCATGGATTATAAGCAGACCCAGCTGTGCCT
[3056] GATCGGCTGTAAGCCACCAATCGGAGAGCACTGGGGCAAGGGCTCTCCATGCAC
[3057] AAATGTGGCCGTGAACCCCGGCGATTGTCCTCCACTGGAGCTGATCAATACCGTG
[3058] ATCCAGGACGGCGATATGGTGGACACAGGCTTCGGCGCCATGGACTTCACCACC
[3059] CTGCAGGCCAACAAGAGCGAGGTGCCTCTGGACATCTGCACCTCCATCTGTAAGT
[3060] ACCCCGATTATATCAAGATGGTGTCCGAGCCTTACGGCGACTCTCTGTTCTTTTAT
[3061] CTGCGGAGAGAGCAGATGTTCGTGAGGCACCTGTTTAATAGGGCAGGAGCAGTG
[3062] GGAGAGAACGTGCCAGACGATCTGTACATCAAGGGCTCCGGCTCTACCGCCAAT
[3063] CTGGCCAGCTCCAACTATTTCCCTACCCCAAGCGGCTCCATGGTGACAAGCGATG
[3064] CCCAGATCTTTAACAAGCCATACTGGCTGCAGAGGGCACAGGGACACAATAACG
[3065] GCATCTGCTGGGGCAATCAGCTGTTCGTGACCGTGGTGGACACCACACGCTCTAC
[3066] AAACATGAGCCTGTGCGCCGCCATCTCTACCAGCGAGACCACATACAAGAACAC
[3067] AAACTTTAAGGAGTACCTGCGGCACGGCGAGGAGTATGACCTGCAGTTCATCTTT
[3068] CAGCTGTGCAAGATCACCCTGACAGCCGATGTGATGACCTACATCCACTCCATGA
[3069] ACAGCACAATCCTGGAGGACTGGAACTTCGGACTGCAGCCACCTCCAGGAGGCA
[3070] CCCTGATCCCAGTGCTGGACGAGAATGGCCTGTTCGCCCCCGAGGATACCTATAG
[3071] GTTTGTGACAAGCCAGGCCATCGCATGTCAGAAGCACACCCCACCTGCACCAAA
[3072] GGAGGACCCCCTGAAGAAGTACACATTCTGGGAGGTGAACCTGAAGGAGAAGTT
[3073] TTCCGCCGACCTGGATCAGTTCCCACTGGGACGGAAGTTTCTGCTGCAGGCAGGC
[3074] CTGAAGGCAAAGCCAAAGTTTACCCTGGGCAAGAGAAAGGCCACCCCTACCACA
[3075] TCTAGCACATCCACCACAGCCAAGCGGAAGAAGAGAAAGCTGTGAGGATCCCTC
[3076] GAGCTCTCTAGAGTCCGCAAAAATCACCAGTCTCTCTCTACAAATCTATCTCTCTC TATTTTTCTCCAGAATAATGTGTGAGTAGTTCCCAGATAAGGGAATTAGGGTTCT
[3077] TATAGGGTTTCGCTCATGTGTTGAGCATATAAGAAACCCTTAGTATGTATTTGTAT
[3078] TTGTAAAATACTTCTATCAATAAAATTTCTAATTCCTAAAACCAAAATCCAGTGA
[3079] CCGGGCGGCGGGTCGAGAATGATTATTTTATGAATATATTTCATTGTGCAAGTAG
[3080] ATAGAAATTACATATGTTACATAACACACGAAATAAACAAAAAAAGACAATCCA
[3081] AAAACAAACACCCCAAAAAAAATAATCACTTTAGATAAACTCGTATGAGGAGAG
[3082] GCACGTTCAGTGACTCGACGATTCCCGAGCAAAAAAAGTCTCCCCGTCACACATA
[3083] TAGTGGGTGACGCAATTATCTTTAAAGTAATCCTTCTGTTGACTTGTCATTGATAA
[3084] CATCCAGTCTTCGTCAGGATTGCAAAGAATTATAGAAGGGATCCCACCTTTTATT
[3085] TTCTTCTTTTTTCCATATTTAGGGTTGACAGTGAAATCAGACTGGCAACCTATTAA
[3086] TTGCTTCCACAATGGGACGAACTTGAAGGGGATGTCGTCGATGATATTATAGGTG
[3087] GCGTGTTCATCGTAGTTGGTGAAATCGATGGTACCGTTCCAATAGTTGTGTCGTC
[3088] CGAGACTTCTAGCCCAGGTGGTCTTTCCGGTACGAGTTGGTCCGCAGATGTAGAG
[3089] GCTGGGGTGTCGGATTCCATTCCTTCCATTGTCCTGGTTAAATCGGCCATCCATTC
[3090] AAGGTCAGATTGAGCTTGTTGGTATGAGACAGGATGTATGTAAGTATAAGCGTCT
[3091] ATGCTTACATGGTATAGATGGGTTTCCCTCCAGGAGTGTAGATCTTCGTGGCAGC
[3092] GAAGATCTGATTCTGTGAAGGGCGACACATACGGTTCAGGTTGTGGAGGGAATA
[3093] ATTTGTTGGCTGAATATTCCAGCCATTGAAGTTTTGTTGCCCATTCATGAGGGAAT
[3094] TCTTCCTTGATCATGTCAAGATATTCCTCCTTAGACGTTGCAGTCTGGATAATAGT
[3095] TCTCCATCGTGCGTCAGATTTGCGAGGAGAGACCTTATGATCTCGGAAATCTCCT
[3096] CTGGTTTTAATATCTCCGTCCTTTGATATGTAATCAAGGACTTGTTTAGAGTTTCT
[3097] AGCTGGCTGGATATTAGGGTGATTTCCTTCAAAATCGAAAAAAGAAGGATCCCT
[3098] AATACAAGGTTTTTTATCAAGCTGGAGAAGAGCATGATAGTGGGTAGTGCCATCT
[3099] TGATGAAGCTCAGAAGCAACACCAAGGAAGAAAATAAGAAAAGGTGTGAGTTTC
[3100] TCCCAGAGAAACTGGAATAAATCATCTCTTTGAGATGAGCACTTGGGATAGGTA
[3101] AGGAAAACATATTTAGATTGGAGTCTGAAGTTCTTACTAGCAGAAGGCATGTTGT
[3102] TGTGACTCCGAGGGGTTGCCTCAAACTCTATCTTATAACCGGCGTGGAGGCATGG
[3103] AGGCAGGGGTATTTTGGTCATTTTAATAGATAGTGGAAAATGACGTGGAATTTAC
[3104] TTAAAGACGAAGTCTTTGCGACAAGGGGGGGCCCACGCCGAATTTAATATTACC
[3105] GGCGTGGCCCCCCCTTATCGCGAGTGCTTTAGCACGAGCGGTCCAGATTTAAAGT
[3106] AGAAAATTTCCCGCCCACTAGGGTTAAAGGTGTTCACACTATACAAGCATATACG
[3107] ATGTGATGGTATTGACTAGAGTTTAAACTATCAGTGTTTGACAGGATATATTGGC
[3108] GGGTAAACCTAAGAGAAAAGAGCGTTTATTAGAATAATCGGATATTTAAAAGGG CGTGAAAAGGTTTATCCGTTCGTCCATTTGTATGTGTACATCACCGACGAGCAAG
[3109] GCAAGACCGAGCGCCTTTCCGACGCTCACCGGGCTGGTTGCCCTCGCCGCTGGGC
[3110] TGGCGGCCGTCTATGGCCCTGCAAACGCGCCAGAAACGCCGTCGAAGCCGTGTG
[3111] CGAGACACCGGCCGCCGGCGTTGTGGATACCTCGCGGAAAACTTGGCCCTCACT
[3112] GACAGATGAGGGGCGGACGTTGACACTTGAGGGGCCGACTCACCCGGCGCGGCG
[3113] TTGACAGATGAGGGGCAGGCTCGATTTCGGCCGGCGACGTGGAGCTGGCCAGCC
[3114] TCGCAAATCGGCGAAAACGCCTGATTTTACGCGAGTTTCCCACAGATGATGTGGA
[3115] CAAGCCTGGGGATAAGTGCCCTGCGGTATTGACACTTGAGGGGCGCGACTACTG
[3116] ACAGATGAGGGGCGCGATCCTTGACACTTGAGGGGCAGAGTGCTGACAGATGAG
[3117] GGGCGCACCTATTGACATTTGAGGGGCTGTCCACAGGCAGAAAATCCAGCATTT
[3118] GCAAGGGTTTCCGCCCGTTTTTCGGCCACCGCTAACCTGTCTTTTAACCTGCTTTT
[3119] AAACCAATATTTATAAACCTTGTTTTTAACCAGGGCTGCGCCCTGTGCGCGTGAC
[3120] CGCGCACGCCGAAGGGGGGTGCCCCCCCTTCTCGAACCCTCCCGGCCCGCTAACG
[3121] CGGGCCTCCCATCCCCCCAGGGGCTGCGCCCCTCGGCCGCGAACGGCCTCACCCC
[3122] AAAAATGGCAGCGCTGGCAGTCCTTGCCATTGCCGGGATCGGGGCAGTAACGGG
[3123] ATGGGCGATCAGCCCGAAAGCTACCCCTATTTGTTTATTTTTCTAAATACATTCAA
[3124] ATATGTATCCGCTCATGAGACAATAACCCTGATAAATGCTTCAATAATATTGAAA
[3125] AAGGAAGAGTATGAGTATTCAACATTTCCGTGTCGCCCTTATTCCCTTTTTTGCGG
[3126] CATTTTGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTAAAAGATGC
[3127] TGAAGATCAGTTGGGTGCACGAGTGGGTTACATCGAACTGGATCTCAACAGCGG
[3128] TAAGATCCTTGAGAGTTTTCGCCCCGAAGAACGTTTTCCAATGATGAGCACTTTT
[3129] AAAGTTCTGCTATGTGGCGCGGTATTATCCCGTATTGACGCCGGGCAAGAGCAAC
[3130] TCGGTCGCCGCATACACTATTCTCAGAATGACTTGGTTGAGTACTCACCAGTCAC
[3131] AGAAAAGCATCTTACGGATGGCATGACAGTAAGAGAATTATGCAGTGCTGCCAT
[3132] AACCATGAGTGATAACACTGCGGCCAACTTACTTCTGACAACGATCGGAGGACC
[3133] GAAGGAGCTAACCGCTTTTTTGCACAACATGGGGGATCATGTAACTCGCCTTGAT
[3134] CGTTGGGAACCGGAGCTGAATGAAGCCATACCAAACGACGAGCGTGACACCACG
[3135] ATGCCTGTAGCAATGGCAACAACGTTGCGCAAACTATTAACTGGCGAACTACTTA
[3136] CTCTAGCTTCCCGGCAACAATTAATAGACTGGATGGAGGCGGATAAAGTTGCAG
[3137] GACCACTTCTGCGCTCGGCCCTTCCGGCTGGCTGGTTTATTGCTGATAAATCTGG
[3138] AGCCGGTGAGCGTGGGTCTCGCGGTATCATTGCAGCACTGGGGCCAGATGGTAA
[3139] GCCCTCCCGTATCGTAGTTATCTACACGACGGGGAGTCAGGCAACTATGGATGAA
[3140] CGAAATAGACAGATCGCTGAGATAGGTGCCTCACTGATTAAGCATTGGTAACTGT CAGACCAAGTTTACTCATATATACTTTAGATTGATTTAAAACTTCATTTTTAATTT
[3141] AAAAGGATCTAGGTGAAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTAAC
[3142] GTGAGTTTTCGTTCCACTGAGCGTCAGACCCCGTAGAAAAGATCAAAGGATCTTC
[3143] TTGAGATCCTTTTTTTCTGCGCGTAATCTGCTGCTTGCAAACAAAAAAACCACCG
[3144] CTACCAGCGGTGGTTTGTTTGCCGGATCAAGAGCTACCAACTCTTTTTCCGAAGG
[3145] TAACTGGCTTCAGCAGAGCGCAGATACCAAATACTGTTCTTCTAGTGTAGCCGTA
[3146] GTTAGGCCACCACTTCAAGAACTCTGTAGCACCGCCTACATACCTCGCTCTGCTA
[3147] ATCCTGTTACCAGTGGCTGCTGCCAGTGGCGATAAGTCGTGTCTTACCGGGTTGG
[3148] ACTCAAGACGATAGTTACCGGATAAGGCGCAGCGGTCGGGCTGAACGGGGGGTT
[3149] CGTGCACACAGCCCAGCTTGGAGCGAACGACCTACACCGAACTGAGATACCTAC
[3150] AGCGTGAGCTATGAGAAAGCGCCACGCTTCCCGAAGGGAGAAAGGCGGACAGG
[3151] TATCCGGTAAGCGGCAGGGTCGGAACAGGAGAGCGCACGAGGGAGCTTCCAGG
[3152] GGGAAACGCCTGGTATCTTTATAGTCCTGTCGGGTTTCGCCACCTCTGACTTGAG
[3153] CGTCGATTTTTGTGATGCTCGTCAGGGGGGCGGAGCCTATGGAAAAACGCCAGC
[3154] AACGCGGCCTTTTTACGGTTCCTGGCCTTTTGCTGGCCTTTTGCTCACATGGACTC
[3155] TAGCTAGAGGATCACAGGCAGCAACGCTCTGTCATCGTTACAATCAACATGCTAC
[3156] CCTCCGCGAGATCATCCGTGTTTCAAACCCGGCAGCTTAGTTGCCGTTCTTCCGA
[3157] ATAGCATCGGTAACATGAGCAAAGTCTGCCGCCTTACAACGGCTCTCCCGCTGAC
[3158] GCCGTCCCGGACTGATGGGCTGCCTGTATCGAGTGGTGATTTTGTGCCGAGCTGC
[3159] CGGTCGGGGAGCTGTTGGCTGGCTGGTGGCAGGATATATTGTGGTGTAAACAAA
[3160] TTGACGCTTAGACAACTTAATAACACATTGCGGACGTTTTTAATGATCGAATACT AACGTCTCTACCACATT
[3161] 40. SEQ ID NO: 40 - pRIC3 L1:2C7 h4_s (Generation II)
[3162] GAAGAGCGTGACTCCGAGGGGTTGCCTCAAACTCTATCTTATAACCGGCGTGGA
[3163] GGCATGGAGGCAGGGGTATTTTGGTCATTTTAATAGATAGTGGAAAATGACGTG
[3164] GAATTTACTTAAAGACGAAGTCTTTGCGACAAGGGGGGGCCCACGCCGAATTTA
[3165] ATATTACCGGCGTGGCCCCCCCTTATCGCGAGTGCTTTAGCACGAGCGGTCCAGA
[3166] TTTAAAGTAGAAAATTTCCCGCCCACTAGGGTTAAAGGTGTTCACACTATAAAAG
[3167] CATATACGATGTGATGGTATTTGCTCGACCTGGTCCAAAGACCAGAGGGCTATTG
[3168] AGACTTTTCAACAAAGGGTAATATCGGGAAACCTCCTCGGATTCCATTGCCCAGC
[3169] TATCTGTCACTTCATCGAAAGGACAGTAGAAAAGGAAGATGGCTTCTACAAATG
[3170] CCATCATTGCGATAAAGGAAAGGCTATCGTTCAAGATGCCTCTACCGACAGTGGT CCCAAAGATGGACCCCCACCCACGAGGAACATCGTGGAAAAAGAAGACGTTCCA
[3171] ACCACGTCTTCAAAGCAAGTGGATTGATGTGATACATGGTGGAGCACGACACTCT
[3172] CGTCTACTCCAAGAATATCAAAGATACAGTCTCAGAAGACCAGAGGGCTATTGA
[3173] GACTTTTCAACAAAGGGTAATATCGGGAAACCTCCTCGGATTCCATTGCCCAGCT
[3174] ATCTGTCACTTCATCGAAAGGACAGTAGAAAAGGAAGATGGCTTCTACAAATGC
[3175] CATCATTGCGATAAAGGAAAGGCTATCGTTCAAGATGCCTCTACCGACAGTGGTC
[3176] CCAAAGATGGACCCCCACCCACGAGGAACATCGTGGAAAAAGAAGACGTTCCAA
[3177] CCACGTCTTCAAAGCAAGTGGATTGATGTGATATCTCCACTGACGTAAGGGATGA
[3178] CGCACAATCCCACTATCCTTCGCAAGACCCTTCCTCTATATAAGGAAGTTCATTTC
[3179] ATTTGGAGAGGACACGCTGAGTTCACAACACAAATCAGATTTATAGAGAGATTT
[3180] ATAAAAAAAAAAAAACATGAGCCTGTGGCTGCCTTCCGAGGCCACAGTGTACCT
[3181] GCCCCCTGTGCCAGTGAGCAAGGTGGTGTCCACCGATGAGTATGTGGCCCGGAC
[3182] AAATATCTACTATCACGCAGGCACCTCTAGACTGCTGGCAGTGGGCCACCCCTAC
[3183] TTCCCTATCAAGAAGCCCAACAATAACAAGATCCTGGTGCCTAAGGTGTCTGGCC
[3184] TGCAGTATAGGGTGTTCCGCATCCACCTGCCAGACCCCAATAAGTTCGGCTTTCC
[3185] TGACACCAGCTTTTACAACCC...
Claims
CLAIMSWhat is claimed is:
1. A human papillomavirus (HPV) virus-like particle (VLP) comprising a chimeric polypeptide comprising: a. an HPV polypeptide, and b. a peptide mimic derived from Neisseria gonorrhoeae (N. gonorrhoeae).
2. The HPV VLP of claim 1, wherein the chimeric polypeptide comprises at least 70% identity to SEQ ID NO: 2, or derivatives thereof.
3. The HPV VLP of claim 1, wherein the chimeric polypeptide comprises at least 80% identity to SEQ ID NO: 2, or derivatives thereof.
4. The HPV VLP of claim 1, wherein the chimeric polypeptide comprises at least 90% identity to SEQ ID NO: 2, or derivatives thereof.
5. The HPV VLP of claim 1, wherein the chimeric polypeptide comprises SEQ ID NO: 2, or derivatives thereof.
6. The HPV VLP of any one of claims 1-5, wherein the chimeric polypeptide is encoded by a nucleic acid sequence comprising at least 70% sequence identity to SEQ ID NO: 1, or derivatives thereof.
7. The HPV VLP of any one of claims 1-5, wherein the chimeric polypeptide is encoded by a nucleic acid sequence comprising at least 80% sequence identity to SEQ ID NO: 1, or derivatives thereof.
8. The HPV VLP of any one of claims 1-5, wherein the chimeric polypeptide is encoded by a nucleic acid sequence comprising at least 90% sequence identity to SEQ ID NO: 1, or derivatives thereof.
9. The HPV VLP of any one of claims 1-5, wherein the chimeric polypeptide is encoded by a nucleic acid sequence comprising SEQ ID NO: 1, or derivatives thereof.
10. The HPV VLP of any one of claims 1-9, wherein the peptide mimic comprises a 2C7 peptide.
11. The HPV VLP of any one of claims 1-10, wherein the peptide mimic comprises SEQ ID NO: 21, SEQ ID NO: 23, or derivatives thereof.
12. The HPV VLP of any one of claims 1-11, wherein the peptide mimic is encoded by a nucleic acid sequence comprising SEQ ID NO: 22, SEQ ID NO: 24, or derivatives thereof.
13. The HPV VLP of any one of claims 1-12, wherein the peptide mimic comprises an epitope.
14. The HPV VLP of any one of claims 1-13, wherein the HPV polypeptide comprises SEQ ID NO: 20, or derivatives thereof.
15. The HPV VLP of any one of claims 1-14, wherein the HPV polypeptide is encoded by a nucleic acid comprising SEQ ID NO: 19, or derivatives thereof.
16. The HPV VLP of any one of claims 1-15, wherein the HPV polypeptide is derived from an HPV 16 virus.
17. The HPV VLP of any one of claims 1-16, wherein the peptide mimic is inserted into the HPV polypeptide.
18. The HPV VLP of any one of claims 1-17, wherein the peptide mimic is inserted into an LI capsid peptide.
19. The HPV VLP of claim 18, wherein the LI capsid peptide comprises a DE loop.
20. The HPV VLP of any one of claims 1-19, wherein the peptide mimic is inserted between amino acids 131 and 132 of a DE loop.
21. A vaccine comprising the human papillomavirus (HPV) virus-like particle (VLP) of any one of claims 1-20, and a pharmaceutically acceptable carrier selected from an excipient, a diluent, a salt, a buffer, a stabilizer, a lipid, or an emulsion.
22. A method of inducing an immune response to a human papillomavirus (HPV), Neisseria gonorrhoeae (N. gonorrhoeae), or combinations thereof, the method comprising administering to a subject an HPV virus-like particle (VLP) vaccine comprising: a. chimeric polypeptide comprising an HPV polypeptide and a peptide mimic derived from N. gonorrhoeae, and b. a pharmaceutically acceptable carrier selected from an excipient, a diluent, a salt, a buffer, a stabilizer, a lipid, or an emulsion.
23. The method of claim 22, wherein the chimeric polypeptide comprises at least 70% identity to SEQ ID NO: 2, or derivatives thereof.
24. The method of claim 22, wherein the chimeric polypeptide comprises at least 80% identity to SEQ ID NO: 2, or derivatives thereof.
25. The method of claim 22, wherein the chimeric polypeptide comprises at least 90% identity to SEQ ID NO: 2, or derivatives thereof.
26. The method of claim 22, wherein the chimeric polypeptide comprises SEQ ID NO: 2, or derivatives thereof.
27. The method of any one of claims 22-26, wherein the chimeric polypeptide is encoded by a nucleic acid sequence comprising at least 70% sequence identity to SEQ ID NO: 1, or derivatives thereof.
28. The method of any one of claims 22-26, wherein the chimeric polypeptide is encoded by a nucleic acid sequence comprising at least 80% sequence identity to SEQ ID NO: 1, or derivatives thereof.
29. The method of any one of claims 22-26, wherein the chimeric polypeptide is encoded by a nucleic acid sequence comprising at least 90% sequence identity to SEQ ID NO: 1, or derivatives thereof.
30. The method of any one of claims 22-26, wherein the chimeric polypeptide is encoded by a nucleic acid sequence comprising SEQ ID NO: 1, or derivatives thereof.
31. The method of any one of claims 22-30, wherein the peptide mimic comprises a 2C7 peptide.
32. The method of any one of claims 22-31 , wherein the peptide mimic comprises SEQ ID NO: 21, SEQ ID NO: 23, or derivatives thereof.
33. The method of any one of claims 22-32, wherein the peptide mimic is encoded by a nucleic acid sequence comprising SEQ ID NO: 22, SEQ ID NO: 24, or derivatives thereof.
34. The method of any one of claims 22-33, wherein the peptide mimic comprises an epitope.
35. The method of any one of claims 22-34, wherein the HPV polypeptide comprises SEQ ID NO: 20, or derivatives thereof.
36. The method of any one of claims 22-35, wherein the HPV polypeptide is encoded by a nucleic acid comprising SEQ ID NO: 19, or derivatives thereof.
37. The method of any one of claims 22-36, wherein the HPV polypeptide is derived from an HPV 16 virus.
38. The method of any one of claims 22-37, wherein the peptide mimic is inserted into the HPV polypeptide.
39. The method of any one of claims 22-38, wherein the peptide mimic is inserted into an LI capsid peptide.
40. The method of claim 39, wherein the LI capsid peptide comprises a DE loop.
41. The method of any one of claims 22-40, wherein the peptide mimic is inserted between amino acids 131 and 132 of a DE loop.
42. The method of any one of claims 22-41, wherein the immune response comprises an antibody response against an N. gonorrhoeae bacterium, a human papillomavirus, or combination thereof.
43. The method of any one of claims 22-42, wherein the immune response comprises clearance of an N. gonorrhoeae bacterium, the human papillomavirus, or combination thereof.
44. A method of preventing an infection from a human papillomavirus (HPV), Neisseria gonorrhoeae (N. gonorrhoeae), or combinations thereof, the method comprising administering to a subject a vaccine comprising an HPV virus-like particle (VLP) comprising: a. chimeric polypeptide comprising an HPV polypeptide and a peptide mimic derived from N. gonorrhoeae, and b. a pharmaceutically acceptable carrier selected from an excipient, a diluent, a salt, a buffer, a stabilizer, a lipid, or an emulsion.
45. The method of claim 44, wherein the chimeric polypeptide comprises at least 70% identity to SEQ ID NO: 2, or derivatives thereof.
46. The method of claim 44, wherein the chimeric polypeptide comprises at least 80% identity to SEQ ID NO: 2, or derivatives thereof.
47. The method of claim 44, wherein the chimeric polypeptide comprises at least 90% identity to SEQ ID NO: 2, or derivatives thereof.
48. The method of claim 44, wherein the chimeric polypeptide comprises SEQ ID NO: 2, or derivatives thereof.
49. The method of any one of claims 44-48, wherein the chimeric polypeptide is encoded by a nucleic acid sequence comprising at least 70% sequence identity to SEQ ID NO: 1, or derivatives thereof.
50. The method of any one of claims 44-48, wherein the chimeric polypeptide is encoded by a nucleic acid sequence comprising at least 80% sequence identity to SEQ ID NO: 1, or derivatives thereof.
51. The method of any one of claims 44-48, wherein the chimeric polypeptide is encoded by a nucleic acid sequence comprising at least 90% sequence identity to SEQ ID NO: 1, or derivatives thereof.
52. The method of any one of claims 44-48, wherein the chimeric polypeptide is encoded by a nucleic acid sequence comprising SEQ ID NO: 1, or derivatives thereof.
53. The method of any one of claims 44-52, wherein the peptide mimic comprises a 2C7 peptide.
54. The method of any one of claims 44-53, wherein the peptide mimic comprises SEQ ID NO: 21, SEQ ID NO: 23, or derivatives thereof.
55. The method of any one of claims 44-54, wherein the peptide mimic is encoded by a nucleic acid sequence comprising SEQ ID NO: 22, SEQ ID NO: 24, or derivatives thereof.
56. The method of any one of claims 44-55, wherein the peptide mimic comprises an epitope.
57. The method of any one of claims 44-56, wherein the HPV polypeptide comprises SEQ ID NO: 20, or derivatives thereof.
58. The method of any one of claims 44-57, wherein the HPV polypeptide is encoded by a nucleic acid comprising SEQ ID NO: 19, or derivatives thereof.
59. The method of any one of claims 44-58, wherein the HPV polypeptide is derived from an HPV 16 virus.
60. The method of any one of claims 44-59, wherein the peptide mimic is inserted into the HPV polypeptide.
61. The method of any one of claims 44-60, wherein the peptide mimic is inserted into an LI capsid peptide.
62. The method of claim 61, wherein the LI capsid peptide comprises a DE loop.
63. The method of any one of claims 44-62, wherein the peptide mimic is inserted between amino acids 131 and 132 of a DE loop.
64. The method of any one of claims 44-63, wherein the method induces an immune response against an N. gonorrhoeae bacterium, a human papillomavirus, or combination thereof.
65. The method of any one of claims 44-64, wherein the preventing of an infection from a human papillomavirus (HPV), Neisseria gonorrhoeae (N. gonorrhoeae), or combinations thereof comprises an antibody response to or a clearance of N. gonorrhoeae , the human papillomavirus, or combination thereof.
66. A method of producing the HPV VLP of any one of claims 1-20, the method comprising:a. generating a chimeric nucleic acid sequence by inserting a first nucleic acid sequence encoding the peptide mimic into a second nucleic acid sequence encoding the HPV polypeptide, b. transferring the chimeric nucleic acid sequence into a plant expression vector, c. infiltrating the plant expression vector of step b) into a tobacco plant, d. expressing the HPV VLP in the tobacco plant, wherein the HPV VLP comprises a chimeric polypeptide, and e. purifying the HPV VLP from the tobacco plant.
67. The method of claim 66, wherein the chimeric polypeptide comprises an HPV polypeptide and a peptide mimic derived from N. gonorrhoeae.
68. The method of claim 66 or 67, wherein the first nucleic acid sequence comprises SEQ ID NO: 22, SEQ ID NO: 24, or derivatives thereof.
69. The method of any one of claims 66-68, wherein the second nucleic acid sequence comprises SEQ ID NO: 19, or derivatives thereof.
70. The method of any one of claims 66-69, wherein the plant expression vector comprises SEQ ID NO: 17, SEQ ID NO: 18, or derivatives thereof.
71. The method of any one of claims 66-70, wherein the plant expression vector comprises a pTRAkc-rbcsl vector or a pRIC3 vector.
72. The method of any one of claims 66-71 , wherein the plant expression vector comprises a chloroplast- specific targeting sequence.
73. The method of any one of claims 66-72, wherein the plant expression vector is infiltrated into the tobacco plant using an Agrobacterium-mediated gene transfer method.
74. The method of any one of claims 66-73, wherein the chimeric HPV VLP is purified by ultracentrifugation through an iodixanol density gradient.
75. The method of any one of claims 66-74, wherein the tobacco plant comprises Nicotiana benthamiana (N. benthamiana).
76. The method of any one of claims 66-75, wherein the peptide mimic comprises a 2C7 peptide.
77. The method of any one of claims 66-76, wherein the HPV polypeptide is derived from an HPV 16 virus.
78. A plant expression vector comprising a nucleic acid sequence encoding a chimeric polypeptide comprising an HPV polypeptide and a peptide mimic derived from N. gonorrhoeae, wherein the plant expression vector comprises at least 70% identity to SEQ ID NO: 25, SEQ ID NO: 29, or derivatives thereof.
79. The plant expression vector of claim 78, wherein the plant expression vector and the nucleic acid sequence comprise at least 80% identity to SEQ ID NO: 25, SEQ ID NO: 29, or derivatives thereof.
80. The plant expression vector of claim 78, wherein the plant expression vector and the nucleic acid sequence comprise at least 90% identity to SEQ ID NO: 25, SEQ ID NO: 29, or derivatives thereof.
81. The plant expression vector of claim 78, wherein the plant expression vector and the nucleic acid sequence comprise SEQ ID NO: 25, SEQ ID NO: 29, or derivatives thereof.
82. The plant expression vector of any one of claims 78-81, wherein the nucleic acid sequence comprises SEQ ID NO: 22, SEQ ID NO: 24, or derivatives thereof, inserted into SEQ ID NO: 19, or derivatives thereof.
83. The plant expression vector of any one of claims 78-82, wherein the plant expression vector comprises a pTRAkc-rbcsl-cTP vector or a pRIC3 vector.
84. The plant expression vector of any one of claims 78-83, wherein the plant expression vector comprises a chloroplast-specific targeting sequence.
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