New r2 retrotransposons for gene writing
Patent Information
- Application Number
- AU2025238573
- Authority / Receiving Office
- AU · AU
- Patent Type
- Applications
- Current Assignee / Owner
- Priority Date
- 2024-03-22
- Filing Date
- 2025-03-24
- Publication Date
- 2026-10-08
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Abstract
Description
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application claims the benefit under 35 U.S.C. § 119(e) of the United States Provisional Application Serial Nos. 63 / 569,037 and 63 / 569,042 filed March 22, 2024, the content of which is hereby incorporated by reference in its entirety. REFERENCE TO AN ELECTRONIC SEQUENCE LISTING
[0002] The content of the electronic sequence listing (385419.xml; Size: 560,415 bytes; and Date of Creation: March 21, 2025) is herein incorporated by reference in its entirety. BACKGROUND
[0003] Unlike DNA transposons, which move via a “cut and paste” mechanism, retrotransposons move in a “copy and paste” manner, using RNA as an intermediate. Based on whether they are flanked by long terminal repeat (LTR), retrotransposons are classified as LTR type or non-LTR type. Non-LTR retrotransposons are sub-classified into two major groups, namely long interspersed nuclear elements (LINEs) and short interspersed nuclear elements (SINEs). LINEs are autonomous elements that encode proteins to mediate their own mobility, whereas SINEs are nonautonomous elements that do not encode protein and consequently require LINEs for their propagation.
[0004] Non-LTR retrotransposons are mobilized by a mechanism in which proteins translated from their open reading frame proteins combine with their own mRNA to form a ribonucleoprotein (RNP) complex. The RNP complex is inserted into the target site via a mechanism termed target-primed reverse transcription (TPRT). The TPRT process is initiated by an encoded EN domain that nicks one strand of DNA at a target site and creates a 3’-hydroxyl end, which is used as a primer for reverse transcription of the LINE mRNA onto the DNA target via RT.
[0005] R2 is a long interspersed element (LINE) found in a specific sequence of the 28S rDNA among a wide variety of animals. Known R2 retrotransposons include those from medaka fish Oryzias latipes (R2O1) and from Bombyx mori (R2Bm). Efforts have been made to use these R2 retrotransposons for targeted gene knock-in for practical application such as gene therapy. SUMMARY
[0006] Through bioinformatic approaches with confirmative testing in human cells, the instant inventors discovered highly efficient new R2 retrotransposons from different species. These new retrotransposons, as well as engineered versions thereof, can be suitably used for targeted gene delivery.
[0007] Accordingly, one embodiment of the present disclosure provides a method for inserting an exogenous sequence to a genomic DNA of a cell, comprising introducing to the cell (a) a polypeptide or a first polynucleotide encoding the polypeptide, wherein the polypeptide comprises (i) a DNA binding domain or a CRISPR Cas protein, (ii) a reverse-transcriptase comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 6, 2, 10, 14, 18, 22, 26, 30, 34, 38, 42, 46, 50, 54, 58, 62, 66, 70, 74, 78, 82, 86, 90, 94, 98, 102, 106, 110, 114, 118, 122, 126, 130, 134, 138, 142, 146, 150, 154, 158, 162, 166, 170, 174, 178, 182, 186, 190, 194, 198, 202, 206, 210, 214, 218, 222, 226, 230, 234, 238, 242, 246, 250, 254, 258, 262, 266, 270, 274, 278, 282, 286, 290, 294, 298, 302, 306, 310, 314, 318, 322, 326, 330, 334, 338, 342, 346, 350, 354, 358, 362, 366, 370, 374, 378, 382, 386, 390, 394, 398, 402, 406, 410, 414, 418 and 422, or an amino acid sequence having at least 85% sequence identity to any of the amino acid selected from the group, and (iii) an endonuclease or a nickase, and (b) an RNA comprising (i) a template for the exogenous sequence and (ii) a 3’ UTR, or a second polynucleotide encoding the RNA.
[0008] In some embodiments, the method further comprises introducing the first polynucleotide and the second polynucleotide to the cell. In some embodiments, the first polynucleotide and the second polynucleotide are on a same vector or on separate vectors.
[0009] In some embodiments, the 3’UTR is an R2 retrotransposon 3’ UTR. In some embodiments, the 3’UTR comprise a sequence selected from the group consisting of SEQ ID NO: 8, 4, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100, 104, 108, 112, 116, 120, 124, 128, 132, 136, 140, 144, 148, 152, 156, 160, 164, 168, 172, 176, 180, 184, 188, 192, 196, 200, 204, 208, 212, 216, 220, 224, 228, 232, 236, 240, 244, 248, 252, 256, 260, 264, 268, 272, 276, 280, 284, 288, 292, 296, 300, 304, 308, 312, 316, 320, 324, 328, 332, 336, 340, 344, 348, 352, 356, 360, 364, 368, 372, 376, 380, 384, 388, 392, 396, 400, 404, 408,412,416, 420 and 424.
[0010] In some embodiments, the reverse-transcriptase comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 6, 2, 10, 14, 18, 22, 26, 30, 34, 38, 42, 46, 50, 54, 58, 62, 66, 70, 74, 78, 82, 86, 90, 94, 98, 102, 106, 110, 114, 118, 122, 126, 130, 134, 138, 142, 146, 150, 154, 158, 162, 166, 170, 174, 178, 182, 186, 190, 194, 198, 202, 206, 210, 214, 218, 222, 226, 230, 234, 238, 242, 246, 250, 254, 258, 262, 266, 270, 274, 278, 282, 286, 290, 294, 298, 302, 306, 310, 314, 318, 322, 326, 330, 334, 338, 342, 346, 350, 354, 358, 362, 366, 370, 374, 378, 382, 386, 390, 394, 398, 402, 406, 410, 414, 418 and 422.
[0011] In some embodiments, the polypeptide comprises the endonuclease. In some embodiments, the polypeptide comprises the nickase, which optionally is Cas nickase. In some embodiments, the CRISPR Cas protein is selected from the group consisting of Cas9, Casl2 and Casl3.
[0012] In some embodiments, the DNA binding domain is selected from the group consisting of a transcription activator-like effector (TALE) DNA binding domain, a homeodomain protein, a zinc finger, a helix-turn-helix, a leucine zipper, and a DNA-binding domain of a homing endonuclease, a transposon or retro-transposon.
[0013] In some embodiments, the DNA binding domain is a TALE. In some embodiments, the homing endonuclease is selected from the group consisting of I-Scel, I-Crel and I-Dmol. In some embodiments, the retro-transposon is a long interspersed nuclear element (LINE), optionally selected from the group consisting of RI, R2, R4, R5, R6, R7, R8, and R9.
[0014] In some embodiments, the polypeptide comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 5, 1, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, 53, 57, 61, 65, 69, 73, 77, 81, 85, 89, 93, 97, 101, 105, 109, 113, 117, 121, 125, 129, 133, 137, 141, 145, 149, 153, 157, 161, 165, 169, 173, 177, 181, 185, 189, 193, 197, 201, 205, 209, 213, 217, 221, 225, 229, 233, 237, 241, 245, 249, 253, 257, 261, 265, 269, 273, 277, 281, 285, 289, 293, 297, 301, 305, 309, 313, 317, 321, 325, 329, 333, 337, 341, 345, 349, 353, 357, 361, 365, 369, 373, 377, 381, 385, 389, 393, 397, 401, 405, 409, 413, 417 and 421, or an amino acid sequence having at least 85% sequence identity to any amino acid sequence selected from the group.
[0015] In some embodiments, the polypeptide comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 5, 1, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, 53, 57, 61, 65, 69, 73, 77, 81, 85, 89, 93, 97, 101, 105, 109, 113, 117, 121, 125, 129, 133, 137, 141, 145, 149, 153, 157, 161, 165, 169, 173, 177, 181, 185, 189, 193, 197, 201, 205, 209, 213, 217, 221, 225, 229, 233, 237, 241, 245, 249, 253, 257, 261, 265, 269, 273, 277, 281, 285, 289, 293, 297, 301, 305, 309, 313, 317, 321, 325, 329, 333, 337, 341, 345, 349, 353, 357, 361, 365, 369, 373, 377, 381, 385, 389, 393, 397, 401, 405, 409, 413, 417 and 421.
[0016] In some embodiments, the RNA further comprises a 5’UTR. In some embodiments, the 5’UTR comprises a sequence selected from the group consisting of SEQ ID NO: 7, 3, 11, 15, 19, 23, 27, 31, 35, 39, 43, 47, 51, 55, 59, 63, 67, 71, 75, 79, 83, 87, 91, 95, 99, 103, 107, 111, 115, 119, 123, 127, 131, 135, 139, 143, 147, 151, 155, 159, 163, 167, 171, 175, 179, 183, 187, 191, 195, 199, 203, 207, 211, 215, 219, 223, 227, 231, 235, 239, 243, 247, 251, 255, 259, 263, 267, 271, 275, 279, 283, 287, 291, 295, 299, 303, 307, 311, 315, 319, 323, 327, 331, 335, 339, 343, 347, 351, 355, 359, 363, 367, 371, 375, 379, 383, 387, 391, 395, 399, 403, 407, 411, 415, 419 and 423.
[0017] In some embodiments, the cell is a mammalian cell, preferably a human cell. In some embodiments, the exogenous sequence encodes a protein, preferably a therapeutic protein. BRIEF DESCRIPTION OF THE DRAWINGS
[0018] FIG. 1 shows the integration activities of selected new R2 elements with digital PCR.
[0019] FIG. 2 illustrates the cis and trans configurations for R2-based reverse transcription.
[0020] FIG. 3 shows the gene delivery rates of new R2 elements indicated by the GFP levels.
[0021] FIG. 4 shows representative GFP images and charts indicating the cargo delivery rates of selected R2 elements in a cis configuration.
[0022] FIG. 5 shows representative GFP images and charts indicating the cargo delivery rates of selected R2 elements in a trans configuration.
[0023] FIG. 6 shows the GFP cargo delivery rates of selected R2 elements in a cis configuration.
[0024] FIG. 7 shows the GFP cargo delivery rates of selected R2 elements in a trans configuration, where the RNA templates included pseudouridine-modified nucleotides. DETAILED DESCRIPTION
[0025] The following description sets forth exemplary embodiments of the present technology. It should be recognized, however, that such description is not intended as a limitation on the scope of the present disclosure but is instead provided as a description of exemplary embodiments. Newly Discovered R2 Retrotransposons
[0026] Through bioinformatic approaches with confirmative testing in human cells, the instant inventors discovered highly efficient new R2 retrotransposons. Their retrotransposition activities were confirmed in human cells in vitro.
[0027] Each of the R2 mRNA includes a 5’ untranslated region (UTR), a single open reading frame (ORF) encoding the endonuclease (EN) and reverse-transcriptase (RT) and DNA-binding domains, and a 3’ UTR. The R2 mRNA can anneal with the target site (i.e., the 28S rDNA in the human genome) and initiates the reverse transcription mechanism.
[0028] Generally, each of the R2 retrotransposons includes one or more N-terminal zinc finger domains, a SANT DNA-binding domain, a 3’ UTR binding domain, a template switching domain, a reverse-transcriptase (RT), a C-terminal zinc finger domain (C-ZnF), and an endonuclease (EN). Among them, the RT domain carries the retrotransposition activity, while the other domains are contemplated to be switchable to similar domains. For instance, the N-terminal zinc fingers can be substituted with other DNA binding domains, as discussed below, and so does the EN domain.
[0029] These new R2 retrotransposons, the species with which they are associated, and the corresponding ORF, RT and 5’ - and 3’-UTR sequences, are summarized in Tables A and B. The corresponding sequences are provided in Tables 1 and 2. Table A. Newly Discovered R2 Retrotransposons No. R2 Name Species SEQ ID NO: for ORF RT 5'UTR 3'UTR 1 R2ApuApu ApusApus 1 2 3 4 2 R2AspTig Aspidoscelis tigris 5 6 7 8 3 R2AspTig' Aspidoscelis tigris 9 10 11 12 4 R2ChaBot Charina bottae 13 14 15 16 5 R2ColStr Colius striatus 17 18 19 20 6 R2CroOre Crotalus oregenus helleri 21 22 23 24 7 R2HemCom Hemiprocne comata 25 26 27 28 8 R2MelGeo Melospiza georgiana 29 30 31 32 9 R2PeCa Pelusios castaneus 33 34 35 36 10 R2CarCar Caretta caretta 37 38 39 40 11 R2PhrBla Phrynosoma blainvillii 41 42 43 44 12 R2PoEx Podocnemis expansa 45 46 47 48 13 R2PufMau Puffinus mauretanicus 49 50 51 52 14 R2Hal Haliaeetus albicilla 53 54 55 56 15 R2EmyOrb Emys orbicularis 57 58 59 60 16 R20piFel Opisthorchis felineus 61 62 63 64 17 R2CapEur Caprimulgus europaeus 65 66 67 68 18 R2DeCI Denticeps clupeoides 69 70 71 72 19 R20nki Oncorhynchus kisutch 73 74 75 76 20 R2AhaPra Ahaetulla prasina 77 78 79 80 21 R2AnnSte Anniella stebbinsi 81 82 83 84 22 R2AriEle Arizona Elegans 85 86 87 88 23 R2AspMar Aspidoscelis marmoratus 89 90 91 92 24 R2AzeSeq Azemiops Seq 1 93 94 95 96 25 R2AzeSeq2 Azemiops Seq 2 97 98 99 100 26 R2AzeSeq3 Azemiops Seq 3 101 102 103 104 27 R2ChaBot2 Charina bottae (Second R2) 105 106 107 108 28 R2CroAda Crotalus adamanteus 109 110 111 112 29 R2CucCan Cuculus canorus 113 114 115 116 30 R2HalLeu Haliaeetus leucocephalus 117 118 119 120 31 R2AqCh Aquila chrysaetos chrysaetos 121 122 123 124 32 R2HarHar Harp la harpyja 125 126 127 128 33 R2CorAlt Corapipo Altera 129 130 131 132 34 R2GopFla Gopherus flavomarginatus 133 134 135 136 35 R2MelCri Melozone crissalis 137 138 139 140 36 R2MyCa Myiozetetes cayennensis 141 142 143 144 37 R2PoAt Poecile atricapillus 145 146 147 148 38 R2ChPi Chrysemys Picta 149 150 151 152 39 R2ATLH Aspidoscelis tigris 153 154 155 156 40 R2ATLH' Aspidoscelis tigris 157 158 159 160 41 R2ATLH" Aspidoscelis tigris 161 162 163 164 42 R2Mac Manacus candei 165 166 167 168 43 R2Pif Pipra filicauda 169 170 171 172 44 R2TyAI Tyto alba 173 174 175 176 45 R2ViLa Viper Latastei 177 178 179 180 46 R2Tral Trimeresurus albolabris 181 182 183 184 47 R2Boja Bothrops jararaca 185 186 187 188 48 R2Bofu Boaedon fuliginosus 189 190 191 192 49 R2CroTig Crotalus tigris 193 194 195 196 50 R2GraSmi Grayia smithii 197 198 199 200 51 R2SibCol Sibynophis collaris 201 202 203 204 52 R2LacBil Lacerta bilineata 205 206 207 208 53 R2LiaOli Liasis olivaceus 209 210 211 212 54 R2MasLat Masticophis lateralis 213 214 215 216 55 R2MasLat2 Masticophis lateralis Second R2 217 218 219 220 56 R20xyLep Oxyrhabdium leporinum 221 222 223 224 57 R2PanAII Pantherophis alleghaniensis 225 226 227 228 58 R2PanGut Pantherophis guttatus 229 230 231 232 59 R2VipUrs Vipera ursinii 233 234 235 236 60 R2FasGigl Fasciola gigantica 237 238 239 240 61 R2FasGig2 Fasciola gigantica 241 242 243 244 62 R2FasGig3 Fasciola gigantica 245 246 247 248 63 R2FasGig4 Fasciola gigantica 249 250 251 252 64 R2FasHep Fasciola hepatica 253 254 255 256 65 R20piVivl Opisthorchis viverrini 257 258 259 260 66 R20piViv2 Opisthorchis viverrini 261 262 263 264 67 R20piViv3 Opisthorchis viverrini 265 266 267 268 68 R2CalDaul Calicophoron daubenyi 269 270 271 272 69 R2CalDau2 Calicophoron daubenyi 273 274 275 276 70 R2SchJap Schistosoma japonicum 277 278 279 280 71 R2SchSol Schistocephalus solidus 281 282 283 284 72 R2SpiEri Spirometra erinaceiruropaei 285 286 287 288 73 R2DipCan Dipylidium caninum 289 290 291 292 74 R2MicRuf Micrastur ruficolis 293 294 295 296 75 R2ChaBot Charina bottae 297 298 299 300 76 R2LiaOli Liasis olivaceus 301 302 303 304 77 R2BotJar Bothrops jararaca 305 306 307 308 78 R2BoaFull Boaedon fuliginosus 309 310 311 312 79 R2BoaFul2 Boaedon fuliginosus 313 314 315 316 80 R2TriAlbl Trimeresurus albolabris 317 318 319 320 81 R2TriAlb2 Trimeresurus albolabris 321 322 323 324 82 R2CroTig Crotalus tigris 325 326 327 328 83 R2CroHel Crotalus helleri 329 330 331 332 84 R20xyLepl Oxyrhabdium leporinum 333 334 335 336 85 R20xyLep2 Oxyrhabdium leporinum 337 338 339 340 86 R2AzeFeal Azemiopsfeae 341 342 343 344 87 R2AzeFea2 Azemiopsfeae 345 346 347 348 88 R2SisCat Sistrurus catenatus 349 350 351 352 89 R2VipLat Vipera latastei 353 354 355 356 90 R2VipUrs Vipera ursinii 357 358 359 360 91 R2AhaPra Ahaetulla prasine 361 362 363 364 92 R2PanGut Pantherophis guttauts 365 366 367 368 93 R2MasLatl Masticophis lateralis 369 370 371 372 94 R2MasLat2 Masticophis lateralis 373 374 375 376 95 R2AriEle Arizona elegans 377 378 379 380 96 R2SibCol Sibynophis collaris 381 382 383 384 97 R2GraSmi Grayia smithii 385 386 387 388 98 R2RhaNuc Rhabdophis nuchalis 389 390 391 392 99 R2MyxAsil Myxocyprinus asiaticus 393 394 395 396 100 R2MyxAsi2 Myxocyprinus asiaticus 397 398 399 400 101 R2MyxAsi3 Myxocyprinus asiaticus 401 402 403 404 102 R2AcrFas Acrossocheilusfasciatus 405 406 407 408 103 R2RhiKla Rhinichthys klamathensis 409 410 411 412 104 R2Mobbir Mobula birostris 413 414 415 416 105 R2PetZak Petrocephalus zakoni 417 418 419 420 106 R2Ptesp Pterobdella sp. 421 422 423 424 Engineered R2 Retrotransposons
[0030] The retrotransposition of R2 retrotransposons does not require homology-directed repair (HDR) or donor DNA. Compared to HDR, which is a passive process in cells, reverse transcription of mRNA into cDNA via TPRT using the RT domain shows relatively higher processivity and fidelity, which is advantageous for synthesizing long cDNAs at the target site rather than recombination at the target site as donor DNA.
[0031] It has been demonstrated herein that the newly discovered R2 retrotransposons specifically target the 28S gene in the human genome. Based on sequence analysis, it is contemplated that the specific 28S binding is attributed to the N-terminal zinc finger (ZnF) domains, likely assisted by the SANT DNA-binding domain. Replacement of these N-terminal regions of the R2 proteins, therefore, may alternate the target specificity of the R2 retrotransposons.
[0032] Accordingly, in some embodiments, the present disclosure provides an engineered R2, in the form of a fusion protein, that includes a truncated version of an R2 ORF and one or more other heterologous elements. The truncated R2 ORF, in some embodiments, includes the reversetranscriptase (or a biological variant thereof) of one of the disclosed R2, but does not include portion of the N-terminal region of the R2, such as one or more of the N-Znfl, N-Znf2, N-Znf3, and SANT DNA-Binding Domain.
[0033] In some embodiments, the heterologous elements may be a DNA binding domain or a CRISPR Cas protein and / or an endonuclease or a nickase. It is appreciated that it is not necessary that both elements are heterologous. For instance, the fusion protein can include one or more heterologous DNA binding domains but the native endonuclease. In another example, the fusion protein can include the native DNA binding domains and a heterologous endonuclease.
[0034] Likewise, another embodiment of the present disclosure provides an engineered R2, in the form of a fusion protein, that includes a truncated version of one of the new R2 ORF and one or more other heterologous elements. The truncated R2 ORF, in some embodiments, includes the reverse-transcriptase (or a biological variant thereof) of R2, but does not include portion of the N-terminal region of R2, such as one or more of the N-Znfl, N-Znf2, N-Znf3, and SANT DNA-Binding Domain.
[0035] As used herein, a “biological variant” of a reference protein refers to a protein or fragment that has at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to the reference protein. In some embodiments, the biological variant retains the desired activity (e.g., reverse-transcriptase) of the reference protein. Likewise, a “biological variant” of a reference nucleic acid sequence refers to a nucleic acid sequence or fragment that has at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to the reference nucleic acid sequence. A. Truncated R2 ORF
[0036] As provided, an engineered R2 protein of the present disclosure can include a truncated version of the R2 ORF fused to at least one heterologous element.
[0037] In one embodiment, the truncated R2 ORF includes a reverse-transcriptase comprising the amino acid sequence of any one of SEQ ID NO: 6, 2, 10, 14, 18, 22, 26, 30, 34, 38, 42, 46, 50, 54, 58, 62, 66, 70, 74, 78, 82, 86, 90, 94, 98, 102, 106, 110, 114, 118, 122, 126, 130, 134, 138, 142, 146, 150, 154, 158, 162, 166, 170, 174, 178, 182, 186, 190, 194, 198, 202, 206, 210, 214, 218, 222, 226, 230, 234, 238, 242, 246, 250, 254, 258, 262, 266, 270, 274, 278, 282, 286, 290, 294, 298, 302, 306, 310, 314, 318, 322, 326, 330, 334, 338, 342, 346, 350, 354, 358, 362, 366, 370, 374, 378, 382, 386, 390, 394, 398, 402, 406, 410, 414, 418 and 422 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 6, 2, 10, 14, 18, 22, 26, 30, 34, 38, 42, 46, 50, 54, 58, 62, 66, 70, 74, 78, 82, 86, 90, 94, 98, 102, 106, 110, 114, 118, 122, 126, 130, 134, 138, 142, 146, 150, 154, 158, 162, 166, 170, 174, 178, 182, 186, 190, 194, 198, 202, 206, 210, 214, 218, 222, 226, 230, 234, 238, 242, 246, 250, 254, 258, 262, 266, 270, 274, 278, 282, 286, 290, 294, 298, 302, 306, 310, 314, 318, 322, 326, 330, 334, 338, 342, 346, 350, 354, 358, 362, 366, 370, 374, 378, 382, 386, 390, 394, 398, 402, 406, 410, 414, 418 and 422.
[0038] In one embodiment, the reverse-transcriptase includes the amino acid sequence of SEQ ID NO: 2 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 2. In one embodiment, the reversetranscriptase includes the amino acid sequence of SEQ ID NO: 6 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 6. In one embodiment, the reverse-transcriptase includes the amino acid sequence of SEQ ID NO: 10 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 10.
[0039] In one embodiment, the reverse-transcriptase includes the amino acid sequence of SEQ ID NO: 14 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 14. In one embodiment, the reversetranscriptase includes the amino acid sequence of SEQ ID NO: 18 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 18. In one embodiment, the reverse-transcriptase includes the amino acid sequence of SEQ ID NO: 22 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 22.
[0040] In one embodiment, the reverse-transcriptase includes the amino acid sequence of SEQ ID NO: 26 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 26. In one embodiment, the reversetranscriptase includes the amino acid sequence of SEQ ID NO: 30 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 30. In one embodiment, the reverse-transcriptase includes the amino acid sequence of SEQ ID NO: 34 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 34.
[0041] In one embodiment, the reverse-transcriptase includes the amino acid sequence of SEQ ID NO: 38 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 38. In one embodiment, the reversetranscriptase includes the amino acid sequence of SEQ ID NO: 42 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 42. In one embodiment, the reverse-transcriptase includes the amino acid sequence of SEQ ID NO: 46 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 46.
[0042] In one embodiment, the reverse-transcriptase includes the amino acid sequence of SEQ ID NO: 50 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 50. In one embodiment, the reversetranscriptase includes the amino acid sequence of SEQ ID NO: 54 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 54. In one embodiment, the reverse-transcriptase includes the amino acid sequence of SEQ ID NO: 58 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 58.
[0043] In one embodiment, the reverse-transcriptase includes the amino acid sequence of SEQ ID NO: 62 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 62. In one embodiment, the reversetranscriptase includes the amino acid sequence of SEQ ID NO: 66 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 66. In one embodiment, the reverse-transcriptase includes the amino acid sequence of SEQ ID NO: 70 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 70. In one embodiment, the reversetranscriptase includes the amino acid sequence of SEQ ID NO: 74 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 74.
[0044] In one embodiment, the reverse-transcriptase includes the amino acid sequence of SEQ ID NO: 78 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 78. In one embodiment, the reversetranscriptase includes the amino acid sequence of SEQ ID NO: 82 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 82. In one embodiment, the reverse-transcriptase includes the amino acid sequence of SEQ ID NO: 86 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 86.
[0045] In one embodiment, the reverse-transcriptase includes the amino acid sequence of SEQ ID NO: 90 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 90. In one embodiment, the reversetranscriptase includes the amino acid sequence of SEQ ID NO: 94 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 94. In one embodiment, the reverse-transcriptase includes the amino acid sequence of SEQ ID NO: 98 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 98.
[0046] In one embodiment, the reverse-transcriptase includes the amino acid sequence of SEQ ID NO: 102 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 102. In one embodiment, the reversetranscriptase includes the amino acid sequence of SEQ ID NO: 106 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 106. In one embodiment, the reverse-transcriptase includes the amino acid sequence of SEQ ID NO: 110 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 110.
[0047] In one embodiment, the reverse-transcriptase includes the amino acid sequence of SEQ ID NO: 114 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 114. In one embodiment, the reversetranscriptase includes the amino acid sequence of SEQ ID NO: 118 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 118. In one embodiment, the reverse-transcriptase includes the amino acid sequence of SEQ ID NO: 122 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 122.
[0048] In one embodiment, the reverse-transcriptase includes the amino acid sequence of SEQ ID NO: 126 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 126. In one embodiment, the reversetranscriptase includes the amino acid sequence of SEQ ID NO: 130 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 130. In one embodiment, the reverse-transcriptase includes the amino acid sequence of SEQ ID NO: 134 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 134.
[0049] In one embodiment, the reverse-transcriptase includes the amino acid sequence of SEQ ID NO: 138 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 138. In one embodiment, the reversetranscriptase includes the amino acid sequence of SEQ ID NO: 142 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 142. In one embodiment, the reverse-transcriptase includes the amino acid sequence of SEQ ID NO: 146 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 146.
[0050] In one embodiment, the reverse-transcriptase includes the amino acid sequence of SEQ ID NO: 150 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 150. In one embodiment, the reverse transcriptase includes the amino acid sequence of SEQ ID NO: 154 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 154. In one embodiment, the reverse-transcriptase includes the amino acid sequence of SEQ ID NO: 158 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 158.
[0051] In one embodiment, the reverse-transcriptase includes the amino acid sequence of SEQ ID NO: 162 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 162. In one embodiment, the reversetranscriptase includes the amino acid sequence of SEQ ID NO: 166 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 166. In one embodiment, the reverse-transcriptase includes the amino acid sequence of SEQ ID NO: 170 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 170.
[0052] In one embodiment, the reverse-transcriptase includes the amino acid sequence of SEQ ID NO: 174 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 174. In one embodiment, the reversetranscriptase includes the amino acid sequence of SEQ ID NO: 178 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 178. In one embodiment, the reverse-transcriptase includes the amino acid sequence of SEQ ID NO: 182 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 182.
[0053] In one embodiment, the reverse-transcriptase includes the amino acid sequence of SEQ ID NO: 186 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 186. In one embodiment, the reversetranscriptase includes the amino acid sequence of SEQ ID NO: 190 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 190. In one embodiment, the reverse-transcriptase includes the amino acid sequence of SEQ ID NO: 194 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 194.
[0054] In one embodiment, the reverse-transcriptase includes the amino acid sequence of SEQ ID NO: 198 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 198. In one embodiment, the reversetranscriptase includes the amino acid sequence of SEQ ID NO: 202 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 202. In one embodiment, the reverse-transcriptase includes the amino acid sequence of SEQ ID NO: 206 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 206.
[0055] In one embodiment, the reverse-transcriptase includes the amino acid sequence of SEQ ID NO: 210 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 210. In one embodiment, the reversetranscriptase includes the amino acid sequence of SEQ ID NO: 214 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 214. In one embodiment, the reverse-transcriptase includes the amino acid sequence of SEQ ID NO: 218 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 218.
[0056] In one embodiment, the reverse-transcriptase includes the amino acid sequence of SEQ ID NO: 222 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 222. In one embodiment, the reversetranscriptase includes the amino acid sequence of SEQ ID NO: 226 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 226. In one embodiment, the reverse-transcriptase includes the amino acid sequence of SEQ ID NO: 230 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 230.
[0057] In one embodiment, the reverse-transcriptase includes the amino acid sequence of SEQ ID NO: 234 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 234. In one embodiment, the reversetranscriptase includes the amino acid sequence of SEQ ID NO: 238 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 238. In one embodiment, the reverse-transcriptase includes the amino acid sequence of SEQ ID NO: 242 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 242.
[0058] In one embodiment, the reverse-transcriptase includes the amino acid sequence of SEQ ID NO: 246 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 246. In one embodiment, the reversetranscriptase includes the amino acid sequence of SEQ ID NO: 250 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 250. In one embodiment, the reverse-transcriptase includes the amino acid sequence of SEQ ID NO: 254 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 254.
[0059] In one embodiment, the reverse-transcriptase includes the amino acid sequence of SEQ ID NO: 258 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 258. In one embodiment, the reversetranscriptase includes the amino acid sequence of SEQ ID NO: 262 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 262. In one embodiment, the reverse-transcriptase includes the amino acid sequence of SEQ ID NO: 266 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 266.
[0060] In one embodiment, the reverse-transcriptase includes the amino acid sequence of SEQ ID NO: 270 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 270. In one embodiment, the reversetranscriptase includes the amino acid sequence of SEQ ID NO: 274 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 274. In one embodiment, the reverse-transcriptase includes the amino acid sequence of SEQ ID NO: 278 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 278.
[0061] In one embodiment, the reverse-transcriptase includes the amino acid sequence of SEQ ID NO: 282 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 282. In one embodiment, the reversetranscriptase includes the amino acid sequence of SEQ ID NO: 286 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 286. In one embodiment, the reverse-transcriptase includes the amino acid sequence of SEQ ID NO: 290 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 290.
[0062] In one embodiment, the reverse-transcriptase includes the amino acid sequence of SEQ ID NO: 294 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 294. In one embodiment, the reversetranscriptase includes the amino acid sequence of SEQ ID NO: 298 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 298. In one embodiment, the reverse-transcriptase includes the amino acid sequence of SEQ ID NO: 302 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 302.
[0063] In one embodiment, the reverse-transcriptase includes the amino acid sequence of SEQ ID NO: 306 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 306. In one embodiment, the reversetranscriptase includes the amino acid sequence of SEQ ID NO: 310 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 310. In one embodiment, the reverse-transcriptase includes the amino acid sequence of SEQ ID NO: 314 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 314.
[0064] In one embodiment, the reverse-transcriptase includes the amino acid sequence of SEQ ID NO: 318 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 318. In one embodiment, the reversetranscriptase includes the amino acid sequence of SEQ ID NO: 322 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 322. In one embodiment, the reverse-transcriptase includes the amino acid sequence of SEQ ID NO: 326 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 326.
[0065] In one embodiment, the reverse-transcriptase includes the amino acid sequence of SEQ ID NO: 330 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 330. In one embodiment, the reversetranscriptase includes the amino acid sequence of SEQ ID NO: 334 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 334. In one embodiment, the reverse-transcriptase includes the amino acid sequence of SEQ ID NO: 338 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 338.
[0066] In one embodiment, the reverse-transcriptase includes the amino acid sequence of SEQ ID NO: 342 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 342. In one embodiment, the reversetranscriptase includes the amino acid sequence of SEQ ID NO: 346 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 346. In one embodiment, the reverse-transcriptase includes the amino acid sequence of SEQ ID NO: 350 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 350.
[0067] In one embodiment, the reverse-transcriptase includes the amino acid sequence of SEQ ID NO: 354 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 354. In one embodiment, the reversetranscriptase includes the amino acid sequence of SEQ ID NO: 358 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 358. In one embodiment, the reverse-transcriptase includes the amino acid sequence of SEQ ID NO: 362 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 362.
[0068] In one embodiment, the reverse-transcriptase includes the amino acid sequence of SEQ ID NO: 366 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 366. In one embodiment, the reverse transcriptase includes the amino acid sequence of SEQ ID NO: 370 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 370. In one embodiment, the reverse-transcriptase includes the amino acid sequence of SEQ ID NO: 374 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 374.
[0069] In one embodiment, the reverse-transcriptase includes the amino acid sequence of SEQ ID NO: 378 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 378. In one embodiment, the reversetranscriptase includes the amino acid sequence of SEQ ID NO: 382 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 382. In one embodiment, the reverse-transcriptase includes the amino acid sequence of SEQ ID NO: 386 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 386.
[0070] In one embodiment, the reverse-transcriptase includes the amino acid sequence of SEQ ID NO: 390 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 390. In one embodiment, the reversetranscriptase includes the amino acid sequence of SEQ ID NO: 394 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 394. In one embodiment, the reverse-transcriptase includes the amino acid sequence of SEQ ID NO: 398 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 398.
[0071] In one embodiment, the reverse-transcriptase includes the amino acid sequence of SEQ ID NO: 402 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 402. In one embodiment, the reversetranscriptase includes the amino acid sequence of SEQ ID NO: 406 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 406. In one embodiment, the reverse-transcriptase includes the amino acid sequence of SEQ ID NO: 410 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 410.
[0072] In one embodiment, the reverse-transcriptase includes the amino acid sequence of SEQ ID NO: 414 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 414. In one embodiment, the reversetranscriptase includes the amino acid sequence of SEQ ID NO: 418 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 418. In one embodiment, the reverse-transcriptase includes the amino acid sequence of SEQ ID NO: 422 or an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to SEQ ID NO: 422.
[0073] In some embodiments, the truncated R2 ORF further includes the 3’ UTR binding domain of the R2 ORF. In some embodiments, the truncated R2 ORF further includes the template switching domain of the R2 ORF. In some embodiments, the truncated R2 ORF further includes the C-terminal ZnF. In some embodiments, the truncated R2 ORF further includes the endonuclease domain. In some embodiments, the truncated R2 ORF includes all elements of the wild-type R2 ORF, except those that are specifically substituted with a corresponding heterologous element (e.g., a heterologous endonuclease). B. Heterologous Targeting Domain
[0074] In some embodiments, one or more of the N-terminal ZnF domains is replaced with a heterologous targeting domain (e.g., a DNA-binding domain or a CRISPR Cas protein).
[0075] A “DNA-binding domain” refers to a protein domain capable of binding a nucleic acid sequence of interest, preferably a double strand nucleic acid molecule. The DNA binding domain recognizes and binds nucleic acid at specific polynucleotide sequences, further referred to as “nucleic acid target sequence.” The DNA-binding domain comprises any of the DNA-binding domain known in the art, such as transcription activator-like effector (TALE), homeodomain protein, a zinc finger, a helix-turn-helix, a leucine zipper, and a DNA-binding domain of a homing endonuclease, a transposon or retro-transposon. In certain embodiments, the DNA-binding domain recognizes a target DNA sequence in the genome.
[0076] A “homeodomain protein” consists of three linked alpha helices (helices 1, 2 and 3). Helices 2 and 3 are arranged in a conspicuous helix turn helix motif. A 60 amino acid long region (homeodomain) within helix 3 binds specifically to DNA segments that contain the sequence 5’ATTA3’. In animals, there are 16 major classes of homeodomain protein, ANTP, PRD, PRD-LIKE, POU, HNF, CUT (with four subclasses: ONECUT, CUX, SATB, and CMP), LIM, ZF, CERS, PROS, SIX / SO, plus the TALE superclass with the classes IRO, MKX, TGIF, PBC, and MEIS. Further homeodomain proteins include but not limited to HEX motif, EH1 motif, Octapeptide / Hep / EHl / TN / GEH motif, WRPW motif, TUP1, OAR motif, CUT domain, such as ONECUT, CUX, SATB, CMP domains, COMPASS domain, HNF1A (LFB1) transcription factor, POU, OCT-1, OCT-2, Pit 1, LIM domain, PROSPERO (PROS), SIX / SO and CERS (LASS).
[0077] The “zinc finger” (ZF) includes at least nine types, C2H2, C2HC, C3H, C4, C6, C3HC4, C2HC5, C4HC3, and C8, in which C and H represent cysteine and histidine, respectively. C2H2 zinc finger is a loop of 12 amino acids with two cysteines and two histidines at the base of the loop (Cys2His2 zinc finger motif consisting of an a helix and an antiparallel P sheet) that tetrahedrally coordinate a zinc ion. C2H2 zinc finger is represented by TFIIIA and further comprises Adnp, Tshz, Zeb, Zfhx and Zhx. C2HC-typezinc finger domains, also referred to as retroviral-type (RT) zinc finger sequences, are required for viral genome packaging and RNA or single-stranded DNA binding in eukaryotes. The C3H family proteins are divided into 18 groups based on the different amino acid spacing numbers between C and H in zinc finger motif. C4 finger has one alpha helix and contains a zinc atom bound to four cysteine amino acids. The C4 zinc finger contains a 70 amino acid long region near the zinc atom that binds specifically to DNA segments. The C4 family includes seven types: GAT A, FYVE, TimlO / DDP, LSD1, A20, TFIIB, and Zn-finger in Ran-binding protein. C3HC4-type finger, also termed RING finger, can be categorized into seven types with different conserved motifs, such as RING-H2, RING-HC, RING-v, RING-D, RING-S / T, RING-G and RING-C2. The C2HC5 motif, also referred to as LIM. More information on the zinc finger can be found in the prior art publication, such as Li et al., International Journal of Molecular Sciences, (2020) 21(4):1361. Further examples of the zinc finger proteins include Spl, Glucocorticoid receptor, estrogen receptor, progesterone receptor, thyroid hormone receptor (erbA), retinoid acid receptor, and the vitamin D3 receptor.
[0078] A “leucine zipper” consists of an alpha helix that contains a region in which every seventh amino acid is leucine, which has the effect of lining up all the leucine residues on one side of the alpha helix. The leucine residues allow for the dimerization of the two lecine zipper proteins and formation of Y shaped dimer. Dimerization may occur between two of the same proteins (homodimers, e.g., Jun-Jun) or two different proteins (heterodimers, e.g., Fos-Jun). A leucine zipper contains a 20 amino acid long region that binds specifically to DNA segments. Examples of the Leucine Zipper proteins include but not limited to CCAAT / enhancer binding protein (C / EBP), Cyclic AMP response element binding protein (CREB), Finkel osteogeneic sarcoma virus (Fos) protein, Jun, GCN4, and HSF.
[0079] A “helix loop helix” (HLH) or “helix-turn-helix” consists of a short alpha helix connected by a loop to a loner alpha helix. The loop allows for dimerization of two HLH proteins and formation of Y shaped dimer. The dimerization may occur between two of the same proteins (homo dimers) or two different proteins (heterodimers). Example of HLH domains include but not limited to MyoD, Myc, Pho4, SREBP-la, and Max-Mad.
[0080] A “Transcription Activator like Effector” (TALE) are proteins that are encoded by phytopathogenic bacteria of the genus Xanthomonas and Ralstonia to influence the gene expression of host plant cells during bacterial infection. These proteins are helix-loop-helixcontaining transcriptional factors that comprise a DNA binding region and an N-terminal domain that appears to interact with the bacterial transport machinery for introducing the protein into the plant cell. The C-terminal domain of the TALE protein seems to interact with the plant host's transcriptional machinery to induce expression of sets of plant genes that are beneficial to the invading bacteria. The DNA binding portion of the proteins is found in the middle section of the protein and is made of an array of repeat units, each approximately 33-35 amino acids in length, which have been shown to be responsible for interacting with the target DNA. In a preferred embodiment, said DNA-binding domain is derived from a TALE engineered to bind a specific nucleic acid target sequence. Unlimited examples of the TALE include KNOX and BEL, such as PBC, MEIS, PREP, IRO, MKX and TGIF.
[0081] A “homing endonuclease (HEs)” or meganuleases (MNs), are sequence-specific endonucleases with large cleavage sites (14-25 bp) that can create double-stranded breaks at specific locations. The homing endonucleases are encoded by mobile genetic elements that induce recombination in a process called homing. The homing endonucleases genes (HEGs) have invaded many genomic niches including group I and group II introns. Some HEGs can move from an ORF-containing intron to an “ORF-less” intron. There are four major families of homing endonucleases (HEs), naming is based on conserved amino acid motifs: the H-N-H, HIS-CYS, LAGLIDADG, and GIY-YIG families of HEs. The LAGLIDADG family of HEs is the most frequently encountered among group I introns. However GIY-YIG endonucleases have been identified within numerous group I introns, and LAGLIDADG HEs and the H-N-H domain are present within the ORFs of some group II introns. Additional HE-like proteins have been described, the PD-(D / E)XK HEs are found in bacterial tRNA group I introns, the very-short patch repair (Vsr) endonucleases (a predicted family of phage HEs based on metagenomic), and the Holliday junction resolvase-like HEs found in some phage introns. In certain embodiments of the present disclosure, the homing endonuclease comprises PLScel, Pl-Pful, I-Crel, I-Ceul, I-Dmol, F-TevI, F-TevII, I-TevI, I-TevII, I-Ppol, I-Dirl, I-Njal, I-NanI, I-Nitl, I-SceV, I-SceVI and I-Llal, I-Hmul, I-HmuII, I-TevIII and I-Cmoel. In a particular embodiment, the homing endonuclease is I-Ppol (Intron-Encoded Endonuclease).
[0082] Retrotransposon is a class of eucaryotic genes capable of replicating to new locations within their own genome through an RNA intermediate. Retrotransposons are widespread in metazoan genomes. The proportion of the genome that contains retrotransposons often exceeds that containing DNA transposons, particularly in higher vertebrates such as humans. Most retrotransposons integrate into random sites of the host genome, but some have a sequence preference. In particular, a few non-LTR subclades integrate into the genome in a highly sequence-specific manner. By leaving their 5’ and / or 3’ ends of genomic copies (usually with a poly (A) stretch and target-site duplication (TSD)), the site-specific non-LTR retrotransposons can be searched throughout the DNA database.
[0083] There are five clades of restriction enzyme-like endonuclease (RLE)-encoding elements based on their RT sequence similarity. Most of three clades (NeSL, R2, and R4) are target specific and two clades (HERO and CRE) have some site-specific elements. R2 (R2 clade) was found at a specific sequence in the 28S rDNA of many invertebrate and vertebrate species. R4 in Ascaris himbricoides and Dong (R4 clade) were found at another site of the 28S rDNA and microsatellite TAA repeats, respectively.
[0084] In contrast to RLE-encoding elements, most of the apurinic / apyrimidinic endonuclease (APE)-encoding non-LTR elements do not insert themselves in a sequence-specific manner, but do have weak target-site specificity, e.g., human LI for TAAA repeats. However, two clades of APE-encoding non-LTR elements, Txl and RI, are known to be sequence-specific.
[0085] Among the site-specific non-LTR retrotransposons, RI clade (R1 / R6 / R7 / RT), R2 clade (R2 / R8 / R9), R4 clade (R4) and NeSl clade (R5) target the rRNA genes, whereas R7 and R8 target the 18S rDNA, and RI, R2, R4, R5, R6, R9, and RT target the 28S rDNA. All R-element target sites within 28S and 18S rDNA are highly conserved among organisms (see Fujiwara et al., Microbiology Spectrum, (2015) Vol. 3, Issue 2).
[0086] In a preferred embodiment, the retrotransposon is rDNA specific and comprises RI, R2, R4, R5, R6, R7, R8, R9 and RT. In certain embodiments, the heterologous DNA-binding domain provided herein comprises the DNA-binding domain of any one of the RI, R2, R4, R5, R6, R7, R8, R9 and RT.
[0087] In certain embodiments, the one or more N-terminal ZnF domains is replaced with a CRISPR Cas protein. In certain embodiments, the CRISPR Cas protein comprises Cas9, Casl2a / Cpfl and Casl3. The clustered regularly interspaced short palindromic repeat (CRISPR) / Cas mediated genome editing technology has seen wild use since its invention due to its simplicity and efficiency, leading to a new era of genetic engineering and gene therapy. The targeting and cleavage are achieved by a single CRISPR RNA (“crRNA”)-bound Cas protein in Class 2 CRISPR-Cas systems. Class 2 systems can be subdivided into Type II Cas9 and Type V Casl2 that target DNA, as well as Type VI Casl3 that target RNA. Cas9 and Casl2a / Cpfl have been well studied in the past and broadly harnessed for gene editing in various cell types and organisms in prokaryotes and eukaryotes. Both Cas9 and Casl2 systems utilize guide RNA to recognize the target site and protospacer adjacent motifs (PAMs) to determine the cleavage site and generate double strand breaks. However, the binding and cleavage of DNA by Cas9 and Casl2 are quite different. Cas9 recognizes a 3’-G-rich PAM and produces blunt ends cleaved by the RuvC and HNH domains, whereas Cas 12 recognizes a 5’ T-rich PAM and produces staggered ends cleaved solely by the RuvC domain. Pre-assembled Cas 13 and crRNA recognizes target RNAs. Upon RNA-binding, Cas 13 will undergo a conformational change and induce the catalytic activity of its nuclease domains, resulting in the cleavage of target transcripts. In certain embodiments, the gRNA or the crRNA can be designed to target a DNA sequence in the genome. In certain embodiments, the Cas protein comprises an inactive nuclease domain. In certain embodiments, the Cas protein does not comprise an active nuclease domain.
[0088] In certain embodiments, the guide RNA (“gRNA”) comprises two short, non-coding RNA species referred to as crRNA and trans-acting RNA (“tracrRNA”). In an exemplary system, the gRNA forms a complex with a Cas protein of the present disclosure. The gRNA:Cas protein complex binds a target polynucleotide sequence in the genome. The gRNA can be supplied separately that works with the Cas protein in guiding the Cas protein (or the fusion) to a target location on a genomic sequence.
[0089] In one aspect of the present disclosure, a fusion protein provided herein that comprises a first fragment that is a truncated R2 protein and a second fragment that can be a DNA-binding domain or a CRISPR Cas protein. In certain embodiments, the second fragment is N-terminal to the first fragment. In certain embodiments, the second fragment can be alternatively C-terminal to the first fragment. The first and second fragments can be fused directly or via a linker sequence. C. Heterologous Endonuclease or Nickase
[0090] In some embodiments, the native endonuclease of the R2 ORF can be replaced with a biological variant (e.g., a sequence having at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% sequence identity to the native endonuclease) or a heterologous endonuclease or a nickase.
[0091] An endonuclease is an enzyme that cleaves internal phosphodiester bonds of polynucleotides. These enzymes are either specific or non-specific to the sequences being cleaved. The endonucleases that are specific to a particular sequence are termed restriction endonucleases, which cleave large DNA molecules at specific sequences of four to six nucleotides.
[0092] In some embodiments the endonuclease is a eukaryotic endonuclease. Non-limiting examples include Neurospora endonuclease, SI nuclease, Pl-nuclease, Mung bean nuclease I, Ustilago nuclease, DNase I, AP endonuclease and Endo R. Other examples include Fokl nuclease, type-II restriction 1-like endonucleases (RLE-type nuclease), and RLE-type endonucleases (REL).
[0093] Many known transposons and retrotransposons also include related endonucleases. In some embodiments, the heterologous endonuclease is one from RI, R2, R4, R5, R6, R7, R8, R9 or RT.
[0094] In some embodiments, the R2 endonuclease is substituted with a nickase. A nikcase (or nicking endonuclease) is an enzyme that cuts one strand of a double-stranded DNA at a specific recognition nucleotide sequence, to produce DNA molecules that are nicked. Nickases can be prepared from Cas enzyme with site mutations (e.g., D10A Cas9).
[0095] The heterologous DNA-binding domain / Cas and / or the heterologous endonuclease can be used to the truncated R2 ORF through a linker sequence. The term “linker sequence” refers to an innocuous length of nucleic acid or protein that joins two other sections of nucleic acid or protein.
[0096] Linkers within the scope of the present disclosure are characterized in terms of amino acid content, length, rigidity and secondary structure. Linkers within the scope of the present disclosure separate the first fragment and the second fragment and allow proper folding and functioning of each domain. In this manner, a linker can be tailored to the particular first and second fragments. According to one aspect, functional independence of the structural and fused (heterologous) domains is maximized by a suitable linker to limit steric interference between domains during the export and assembly processes of the bacterial cell. According to an additional aspect, cell stress is minimized by limiting the overall length of the fusion protein. Longer linker sequences and higher induction levels stress the biosynthetic machinery of the cells, inhibiting cell growth and leading to cell lysis in extreme cases.
[0097] Linkers within the scope of the present disclosure facilitate functioning of the first and second fragments. Linkers within the scope of the present disclosure allow efficient protein processing and export through the bacterial curli secretion machinery as well as provide the proper spatial and physicochemical separation of the polypeptides to retain their respective functions.
[0098] Linkers within the scope of the present disclosure include amino acid residues. The amino acid residues may be any of the naturally occurring amino acid residues. Amino acid residues may also be synthetic amino acids known to those of skill in the art. Representative amino acids which may be used in linkers include Glycine, Alanine, Valine, Leucine, Isoleucine, Serine, Cysteine, Selenocysteine, Threonine, Methionine, Proline, Phenylalanine, Tyrosine, Tryptophan, Histidine, Lysine, Arginine, Aspartate, Glutamate, Asparagine, and Glutamine.
[0099] According to one aspect, a linker sequence is a polypeptide sequence of at least 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 24, 48 or more amino acids. In some embodiments, the linker sequence comprises from about 3 amino acids to about 50 amino acids. In some embodiments, the linker sequence comprises from about 3 amino acids to about 40 amino acids. In some embodiments, the linker sequence comprises from about 5 amino acids to about 30 amino acids. In some embodiments, the linker sequence comprises from about 5 amino acids to about 25 amino acids. In some embodiments, the linker sequence comprises from about 5 amino acids to about 24 amino acids. In some embodiments, the linker sequence comprises from about 5 amino acids to about 23 amino acids. In some embodiments, the linker sequence comprises from about 5 amino acids to about 22 amino acids. In some embodiments, the linker sequence comprises from about 5 amino acids to about 21 amino acids. In some embodiments, the linker sequence comprises from about 5 amino acids to about 20 amino acids. In some embodiments, the linker sequence comprises from about 5 amino acids to about 19 amino acids. In some embodiments, the linker sequence comprises from about 5 amino acids to about 18 amino acids. In some embodiments, the linker sequence comprises from about 5 amino acids to about 17 amino acids. In some embodiments, the linker sequence comprises from about 5 amino acids to about 16 amino acids. In some embodiments, the linker sequence comprises from about 5 amino acids to about 15 amino acids. In some embodiments, the linker sequence comprises from about 5 amino acids to about 14 amino acids. In some embodiments, the linker sequence comprises from about 5 amino acids to about 13 amino acids. In some embodiments, the linker sequence comprises from about 5 amino acids to about 12 amino acids. In some embodiments, the linker sequence comprises from about 5 amino acids to about 11 amino acids. In some embodiments, the linker sequence comprises from about 5 amino acids to about 10 amino acids.
[0100] In some embodiments, the linker sequence comprises a flexible polypeptide, e.g., a polypeptide not having a rigid secondary and / or tertiary structure. In some embodiments, the linker sequence comprises glycine and serine residues. In some embodiments at least 50% of the amino acids comprised by the linker sequence are glycine or serine residues, e.g. at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or more are glycine or serine residues. In some embodiments, the linker sequence consists of glycine and serine residues. In some embodiments, the linker sequence comprises a rigid polypeptide.
[0101] In some embodiments, the truncated R2 ORF and the one or more heterologous elements are not delivered and expressed together. Instead, they can be delivered and expressed separately, or are conjugated or bound to one another.
[0102] Therefore, in one aspect, the present disclosure provides a complex comprising a first polypeptide comprising the truncated R2 ORF and a second polypeptide comprising the targeting domain (e.g., a DNA-binding domain or a CRISPR Cas protein) and / or the endonuclease / nickase, wherein the first polypeptide is conjugated or bound to the second polypeptide. The term “conjugate” or “bind” as used herein refers to conjugation of a first conjugation moiety and a second conjugation moiety which form a complex and stabilized by chemical reactions with few of several available chemical groups (chemical conjugation) or via one or more covalent bonds (biological conjugation).
[0103] In certain embodiments, the first polypeptide includes a first conjugation moiety and the second polypeptide comprises a second conjugation moiety, wherein the first polypeptide and the second polypeptide are brought together by the conjugation moi eties and form a stable complex.
[0104] In certain embodiments, the first polypeptide and the second polypeptide may respectfully but regardless of order, further include (a) a receptor and a corresponding ligand, (b) a peptide and a corresponding antibody, or (c) an enzyme and a corresponding substrate. Protein-Coding Sequence for Delivery
[0105] In one embodiment, the R2 ORF, or an engineered version thereof, can be provided as a mRNA. The mRNA can further include the corresponding 5’UTR and / or 3’UTR of the native R2.
[0106] In some embodiments, to insert a different sequence (e.g., a second protein-coding sequence) to a target genome, the mRNA can further include that second protein-coding sequence. In some embodiments, the second protein-coding sequence is 3’ to the R2 ORF. In some embodiments, the second protein-coding sequence is included in the mRNA in a reversecomplement orientation such that it cannot be directly translated by the mRNA. Rather it is translated after integration to the target genome. In some embodiments, the second proteincoding sequence is inserted at 3’ to the R2 ORF via a self-cleaving peptide sequence, such as 2A self-cleaving peptide.
[0107] Alternatively, in some embodiments, the second protein-coding sequence is provided on a separate mRNA that flanks the second protein-coding sequence with the 5’UTR and / or 3’UTR of the native R2.
[0108] In some embodiments, the second protein is a therapeutic protein that can be helpful in treating a disease or condition in a patient. Examples include: - Insulin - used to treat diabetes - Phenylalanine hydroxylase - used to treat PKU (Phenylketonuria) disease - Erythropoietin - used to treat anemia - Filgrastim (G-CSF) - used to treat neutropenia - Interferons - used to treat cancer, multiple sclerosis, and viral infections - Tumor necrosis factor (TNF) inhibitors - used to treat autoimmune diseases, such as rheumatoid arthritis and Crohn's disease - Monoclonal antibodies - used to treat cancer, autoimmune diseases, and some viral infections - Follitropin alfa - used to treat infertility - Coagulation factor - used to treat bleeding disorders, such as Hemophilia - Enzyme replacement therapy enzymes - used to treat lysosomal storage disorders, such as Gaucher's disease - Growth hormone - used to treat growth hormone deficiency.
[0109] In some embodiments, the polynucleotide (e.g., mRNA) further includes a downstream flanking sequence that is 3’ to the protein-coding sequence. Addition of a downstream flanking sequence can improve the retrotransposition efficiency. In certain embodiments, the proteincoding sequence may comprise, at the 3’ end of the gene encoding sequence, one or more consecutive nucleotides (rDNA sequences) of the “downstream sequence” starting from the EN cleavage site. The protein-coding sequence may comprise, at the 3’ end of the gene encoding sequence, different lengths of the downstream sequence depending on the type of polynucleotide or vector used for delivery. In certain embodiments, a length of the downstream sequence of at least 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, 100, 110, 120, 130, 140, 150, 160, 170, 180, 200, 250 nt can be included to the 3’ mRNA of the fusion protein-encoding sequence. In some embodiments, the length can be 1-250, 1-200, 4-180, 10-150, 15-150, 40-90, 50-90, 70-90 or 71-90 nt, without limitation.
[0110] In some embodiments, the polynucleotide (e.g., mRNA) further includes an upstream flanking sequence that is 5’ to the protein-coding sequence. Addition of an upstream flanking sequence may also improve the retrotransposition efficiency. In certain embodiments, the protein-coding sequence may comprise, at the 5’ end of the gene encoding sequence, one or more consecutive nucleotides (rDNA sequences) of the “upstream sequence” starting from the EN cleavage site. The protein-coding sequence may comprise, at the 5’ end of the gene encoding sequence, different lengths of the downstream sequence depending on the type of polynucleotide or vector used for delivery. In certain embodiments, a length of the downstream sequence of at least 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, 100, 110, 120, 130, 140, 150, 160, 170, 180, 200, 250 nt can be included to the 5’ mRNA of the fusion protein-encoding sequence. In some embodiments, the length can be 1-250, 1-200, 4-180, 10-150, 15-150, 40-90, 50-90, 70-90 or 71-90 nt, without limitation. [OlH] In some embodiments, the R2 3’UTR has the nucleic acid sequence of any one of SEQ ID NO: 8, 4, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100, 104, 108, 112, 116, 120, 124, 128, 132, 136, 140, 144, 148, 152, 156, 160, 164, 168, 172, 176, 180, 184, 188, 192, 196, 200, 204, 208, 212, 216, 220, 224, 228, 232, 236, 240, 244, 248, 252, 256, 260, 264, 268, 272, 276, 280, 284, 288, 292, 296, 300, 304, 308, 312, 316, 320, 324, 328, 332, 336, 340, 344, 348, 352, 356, 360, 364, 368, 372, 376, 380, 384, 388, 392, 396, 400, 404, 408, 412, 416, 420 and 424. In some embodiments, the 3’UTR has at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 97%, 98%, 99% or 100% sequence identity to any one of SEQ ID NO: 8, 4, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100, 104, 108, 112, 116, 120, 124, 128, 132, 136, 140, 144, 148, 152, 156, 160, 164, 168, 172, 176, 180, 184, 188, 192, 196, 200, 204, 208, 212, 216, 220, 224, 228, 232, 236, 240, 244, 248, 252, 256, 260, 264, 268, 272, 276, 280, 284, 288, 292, 296, 300, 304, 308, 312, 316, 320, 324, 328, 332, 336, 340, 344, 348, 352, 356, 360, 364, 368, 372, 376, 380, 384, 388, 392, 396, 400, 404, 408, 412, 416, 420 and 424. In some embodiments, the 3’UTR is directly connected to the downstream flanking sequence.
[0112] In some embodiments, the polynucleotide (e.g., mRNA) further includes a 5’ untranslated region (UTR) 5’ to the protein-coding sequence. When an upstream flanking sequence is also included, preferably the upstream flanking sequence is 5’ to the 5’UTR.
[0113] In some embodiments, the R2 5’UTR has the nucleic acid sequence of any one of SEQ ID NO: 7, 3, 11,15, 19, 23, 27, 31, 35, 39, 43, 47, 51, 55, 59, 63, 67, 71, 75, 79, 83, 87, 91, 95, 99, 103, 107, 111, 115, 119, 123, 127, 131, 135, 139, 143, 147, 151, 155, 159, 163, 167, 171, 175, 179, 183, 187, 191, 195, 199, 203, 207, 211, 215, 219, 223, 227, 231, 235, 239, 243, 247, 251, 255, 259, 263, 267, 271, 275, 279, 283, 287, 291, 295, 299, 303, 307, 311, 315, 319, 323, 327, 331, 335, 339, 343, 347, 351, 355, 359, 363, 367, 371, 375, 379, 383, 387, 391, 395, 399, 403, 407, 411,415,419 and 423. In some embodiments, the 5’UTR has at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 97%, 98%, 99% or 100% sequence identity to any one of SEQ ID NO: 7, 3, 11, 15, 19, 23, 27, 31, 35, 39, 43, 47, 51, 55, 59, 63, 67, 71, 75, 79, 83, 87, 91, 95, 99, 103, 107, 111, 115, 119, 123, 127, 131, 135, 139, 143, 147, 151, 155, 159, 163, 167, 171, 175, 179, 183, 187, 191, 195, 199, 203, 207, 211, 215, 219, 223, 227, 231, 235, 239, 243, 247, 251, 255, 259, 263, 267, 271, 275, 279, 283, 287, 291, 295, 299, 303, 307, 311, 315, 319, 323, 327, 331, 335, 339, 343, 347, 351, 355, 359, 363, 367, 371, 375, 379, 383, 387, 391, 395, 399, 403, 407, 411,415, 419 and 423.
[0114] In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO:2 or a biological variant, or the R2 ORF includes SEQ ID NO: 1 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 4 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 3 or a biological variant. In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO:6 or a biological variant, or the R2 ORF includes SEQ ID NO: 5 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 8 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 7 or a biological variant. In some embodiments, the R2 ORF includes an RT that includes SEQ ID NOTO or a biological variant, or the R2 ORF includes SEQ ID NO: 9 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 12 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 11 or a biological variant.
[0115] In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO: 14 or a biological variant, or the R2 ORF includes SEQ ID NO: 13 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 16 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 15 or a biological variant. In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO: 18 or a biological variant, or the R2 ORF includes SEQ ID NO: 17 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 20 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 19 or a biological variant. In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO:22 or a biological variant, or the R2 ORF includes SEQ ID NO: 21 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 24 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 23 or a biological variant.
[0116] In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO:26 or a biological variant, or the R2 ORF includes SEQ ID NO: 25 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 28 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 27 or a biological variant. In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO:30 or a biological variant, or the R2 ORF includes SEQ ID NO: 29 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 32 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 31 or a biological variant. In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO:34 or a biological variant, or the R2 ORF includes SEQ ID NO: 33 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 36 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 35 or a biological variant.
[0117] In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO:38 or a biological variant, or the R2 ORF includes SEQ ID NO: 37 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 40 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 39 or a biological variant. In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO:42 or a biological variant, or the R2 ORF includes SEQ ID NO: 41 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 44 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ LD NO: 43 or a biological variant. In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO:46 or a biological variant, or the R2 ORF includes SEQ ID NO: 45 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 48 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 47 or a biological variant.
[0118] In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO:50 or a biological variant, or the R2 ORF includes SEQ ID NO: 49 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 52 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 51 or a biological variant. In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO:54 or a biological variant, or the R2 ORF includes SEQ ID NO: 53 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 56 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 55 or a biological variant. In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO:58 or a biological variant, or the R2 ORF includes SEQ ID NO: 57 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 60 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 59 or a biological variant.
[0119] In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO:62 or a biological variant, or the R2 ORF includes SEQ ID NO: 61 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 64 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 63 or a biological variant. In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO:66 or a biological variant, or the R2 ORF includes SEQ ID NO: 65 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 68 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 67 or a biological variant. In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO:70 or a biological variant, or the R2 ORF includes SEQ ID NO: 69 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 72 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ LD NO: 71 or a biological variant.
[0120] In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO:74 or a biological variant, or the R2 ORF includes SEQ ID NO: 73 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 76 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 75 or a biological variant. In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO:78 or a biological variant, or the R2 ORF includes SEQ ID NO: 77 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 80 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 79 or a biological variant. In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO:82 or a biological variant, or the R2 ORF includes SEQ ID NO: 81 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 84 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 83 or a biological variant.
[0121] In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO:86 or a biological variant, or the R2 ORF includes SEQ ID NO: 85 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 88 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 87 or a biological variant. In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO:90 or a biological variant, or the R2 ORF includes SEQ ID NO: 89 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 92 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 91 or a biological variant. In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO:94 or a biological variant, or the R2 ORF includes SEQ ID NO: 93 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 96 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 95 or a biological variant.
[0122] In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO:98 or a biological variant, or the R2 ORF includes SEQ ID NO: 97 or a biological variant, and the corresponding R2 3’UTR includes SEQ LD NO: 100 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 99 or a biological variant. In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO: 102 or a biological variant, or the R2 ORF includes SEQ ID NO: 101 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 104 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 103 or a biological variant. In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO: 106 or a biological variant, or the R2 ORF includes SEQ ID NO: 105 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 108 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 107 or a biological variant.
[0123] In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO: 110 or a biological variant, or the R2 ORF includes SEQ ID NO: 109 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 112 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 111 or a biological variant. In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO: 114 or a biological variant, or the R2 ORF includes SEQ ID NO: 113 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 116 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 115 or a biological variant. In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO: 118 or a biological variant, or the R2 ORF includes SEQ ID NO: 117 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 120 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 119 or a biological variant.
[0124] In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO: 122 or a biological variant, or the R2 ORF includes SEQ ID NO: 121 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 124 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 123 or a biological variant. In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO: 126 or a biological variant, or the R2 ORF includes SEQ ID NO: 125 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 128 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 127 or a biological variant. In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO: 130 or a biological variant, or the R2 ORF includes SEQ ID NO: 129 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 132 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 131 or a biological variant.
[0125] In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO: 134 or a biological variant, or the R2 ORF includes SEQ ID NO: 133 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 136 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 135 or a biological variant. In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO: 138 or a biological variant, or the R2 ORF includes SEQ ID NO: 137 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 140 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 139 or a biological variant. In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO: 142 or a biological variant, or the R2 ORF includes SEQ ID NO: 141 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 144 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 143 or a biological variant.
[0126] In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO: 146 or a biological variant, or the R2 ORF includes SEQ ID NO: 145 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 148 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 147 or a biological variant. In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO: 150 or a biological variant, or the R2 ORF includes SEQ ID NO: 149 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 152 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 151 or a biological variant. In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO:154 or a biological variant, or the R2 ORF includes SEQ ID NO: 153 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 156 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 155 or a biological variant.
[0127] In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO: 158 or a biological variant, or the R2 ORF includes SEQ ID NO: 157 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 160 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 159 or a biological variant. In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO: 162 or a biological variant, or the R2 ORF includes SEQ ID NO: 161 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 164 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 163 or a biological variant. In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO: 166 or a biological variant, or the R2 ORF includes SEQ ID NO: 165 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 168 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 167 or a biological variant.
[0128] In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO: 170 or a biological variant, or the R2 ORF includes SEQ ID NO: 169 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 172 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 171 or a biological variant. In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO: 174 or a biological variant, or the R2 ORF includes SEQ ID NO: 173 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 176 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 175 or a biological variant. In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO:178 or a biological variant, or the R2 ORF includes SEQ ID NO: 177 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 180 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 179 or a biological variant.
[0129] In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO: 182 or a biological variant, or the R2 ORF includes SEQ ID NO: 181 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 184 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 183 or a biological variant. In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO: 186 or a biological variant, or the R2 ORF includes SEQ ID NO: 185 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 188 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 187 or a biological variant. In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO: 190 or a biological variant, or the R2 ORF includes SEQ ID NO: 189 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 192 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 191 or a biological variant.
[0130] In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO: 194 or a biological variant, or the R2 ORF includes SEQ ID NO: 193 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 196 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 195 or a biological variant. In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO: 198 or a biological variant, or the R2 ORF includes SEQ ID NO: 197 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 200 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 199 or a biological variant. In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO:202 or a biological variant, or the R2 ORF includes SEQ ID NO: 201 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 204 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 203 or a biological variant.
[0131] In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO:206 or a biological variant, or the R2 ORF includes SEQ ID NO: 205 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 208 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 207 or a biological variant. In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO:210 or a biological variant, or the R2 ORF includes SEQ ID NO: 209 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 212 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 211 or a biological variant. In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO:214 or a biological variant, or the R2 ORF includes SEQ ID NO: 213 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 216 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 215 or a biological variant.
[0132] In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO:218 or a biological variant, or the R2 ORF includes SEQ ID NO: 217 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 220 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 219 or a biological variant. In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO:222 or a biological variant, or the R2 ORF includes SEQ ID NO: 221 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 224 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 223 or a biological variant. In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO:226 or a biological variant, or the R2 ORF includes SEQ ID NO: 225 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 228 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 227 or a biological variant.
[0133] In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO:230 or a biological variant, or the R2 ORF includes SEQ ID NO: 229 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 232 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 231 or a biological variant. In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO:234 or a biological variant, or the R2 ORF includes SEQ ID NO: 233 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 236 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 235 or a biological variant. In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO:238 or a biological variant, or the R2 ORF includes SEQ ID NO: 237 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 240 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 239 or a biological variant.
[0134] In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO:242 or a biological variant, or the R2 ORF includes SEQ ID NO: 241 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 244 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 243 or a biological variant. In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO:246 or a biological variant, or the R2 ORF includes SEQ ID NO: 245 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 248 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 247 or a biological variant. In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO:250 or a biological variant, or the R2 ORF includes SEQ ID NO: 249 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 252 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 251 or a biological variant.
[0135] In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO:254 or a biological variant, or the R2 ORF includes SEQ ID NO: 253 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 256 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 255 or a biological variant. In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO:258 or a biological variant, or the R2 ORF includes SEQ ID NO: 257 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 260 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 259 or a biological variant. In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO:262 or a biological variant, or the R2 ORF includes SEQ ID NO: 261 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 264 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 263 or a biological variant.
[0136] In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO:266 or a biological variant, or the R2 ORF includes SEQ ID NO: 265 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 268 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 267 or a biological variant. In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO:270 or a biological variant, or the R2 ORF includes SEQ ID NO: 269 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 272 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 271 or a biological variant. In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO:274 or a biological variant, or the R2 ORF includes SEQ ID NO: 273 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 276 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 275 or a biological variant.
[0137] In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO:278 or a biological variant, or the R2 ORF includes SEQ ID NO: 277 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 280 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 279 or a biological variant. In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO:282 or a biological variant, or the R2 ORF includes SEQ ID NO: 281 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 284 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 283 or a biological variant. In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO:286 or a biological variant, or the R2 ORF includes SEQ ID NO: 285 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 288 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 287 or a biological variant.
[0138] In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO:290 or a biological variant, or the R2 ORF includes SEQ ID NO: 289 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 292 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 291 or a biological variant. In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO:294 or a biological variant, or the R2 ORF includes SEQ ID NO: 293 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 296 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 295 or a biological variant. In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO:298 or a biological variant, or the R2 ORF includes SEQ ID NO: 297 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 300 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 299 or a biological variant.
[0139] In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO:302 or a biological variant, or the R2 ORF includes SEQ ID NO: 301 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 304 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 303 or a biological variant. In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO:306 or a biological variant, or the R2 ORF includes SEQ ID NO: 305 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 308 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 307 or a biological variant. In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO:310 or a biological variant, or the R2 ORF includes SEQ ID NO: 309 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 312 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 311 or a biological variant.
[0140] In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO:314 or a biological variant, or the R2 ORF includes SEQ ID NO: 313 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 316 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 315 or a biological variant. In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO:318 or a biological variant, or the R2 ORF includes SEQ ID NO: 317 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 320 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 319 or a biological variant. In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO:322 or a biological variant, or the R2 ORF includes SEQ ID NO: 321 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 324 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 323 or a biological variant.
[0141] In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO:326 or a biological variant, or the R2 ORF includes SEQ ID NO: 325 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 328 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 327 or a biological variant. In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO:330 or a biological variant, or the R2 ORF includes SEQ ID NO: 329 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 332 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 331 or a biological variant. In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO:334 or a biological variant, or the R2 ORF includes SEQ ID NO: 333 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 336 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 335 or a biological variant.
[0142] In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO:338 or a biological variant, or the R2 ORF includes SEQ ID NO: 337 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 340 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 339 or a biological variant. In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO:342 or a biological variant, or the R2 ORF includes SEQ ID NO: 341 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 344 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 343 or a biological variant. In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO:346 or a biological variant, or the R2 ORF includes SEQ ID NO: 345 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 348 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 347 or a biological variant.
[0143] In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO:350 or a biological variant, or the R2 ORF includes SEQ ID NO: 349 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 352 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 351 or a biological variant. In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO:354 or a biological variant, or the R2 ORF includes SEQ ID NO: 353 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 356 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 355 or a biological variant. In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO:358 or a biological variant, or the R2 ORF includes SEQ ID NO: 357 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 360 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 359 or a biological variant.
[0144] In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO:362 or a biological variant, or the R2 ORF includes SEQ ID NO: 361 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 364 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 363 or a biological variant. In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO:366 or a biological variant, or the R2 ORF includes SEQ ID NO: 365 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 368 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 367 or a biological variant. In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO:370 or a biological variant, or the R2 ORF includes SEQ ID NO: 369 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 372 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 371 or a biological variant.
[0145] In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO:374 or a biological variant, or the R2 ORF includes SEQ ID NO: 373 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 376 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 375 or a biological variant. In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO:378 or a biological variant, or the R2 ORF includes SEQ ID NO: 377 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 380 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 379 or a biological variant. In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO:382 or a biological variant, or the R2 ORF includes SEQ ID NO: 381 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 384 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 383 or a biological variant.
[0146] In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO:386 or a biological variant, or the R2 ORF includes SEQ ID NO: 385 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 388 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 387 or a biological variant. In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO:390 or a biological variant, or the R2 ORF includes SEQ ID NO: 389 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 392 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 391 or a biological variant. In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO:394 or a biological variant, or the R2 ORF includes SEQ ID NO: 393 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 396 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 395 or a biological variant.
[0147] In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO:398 or a biological variant, or the R2 ORF includes SEQ ID NO: 397 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 400 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 399 or a biological variant. In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO:402 or a biological variant, or the R2 ORF includes SEQ ID NO: 401 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 404 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 403 or a biological variant. In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO:406 or a biological variant, or the R2 ORF includes SEQ ID NO: 405 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 408 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 407 or a biological variant.
[0148] In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO:410 or a biological variant, or the R2 ORF includes SEQ ID NO: 409 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 412 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 411 or a biological variant. In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO:414 or a biological variant, or the R2 ORF includes SEQ ID NO: 413 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 416 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 415 or a biological variant. In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO:418 or a biological variant, or the R2 ORF includes SEQ ID NO: 417 or a biological variant, and the corresponding R2 3’UTR includes SEQ ID NO: 420 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 419 or a biological variant.
[0149] In some embodiments, the R2 ORF includes an RT that includes SEQ ID NO:422 or a biological variant, or the R2 ORF includes SEQ ID NO: 421 or a biological variant, and the corresponding R2 3’UTR includes SEQ LD NO: 424 or a biological variant. In some embodiments, a corresponding R2 5’UTR is used, which includes SEQ ID NO: 423 or a biological variant. Gene Delivery and Treatments
[0150] The R2 retrotransposition systems disclosed here are suitable for delivering exogenous genes to a target cell, such as a mammalian cell.
[0151] Accordingly, in some embodiments, the present disclosure provides a method for integrating an exogenous polynucleotide to the genome of a target cell. In one embodiment, the method entails introducing to the cell the polynucleotide comprising an R2 retrotransposon of the instant disclosure. In some embodiments, the retrotransposon is delivered to the target cell as an mRNA molecule directly.
[0152] In some embodiments, when the polynucleotide comprises a CRISPR Cas protein encoding sequence, the method further comprises introducing to the cell a guide RNA (gRNA) that binds to the CRISPR Cas protein and recognizes a target DNA sequence in the genome.
[0153] mRNAs may be synthesized according to any of a variety of known methods. For example, the mRNAs may be synthesized via in vitro transcription (IVT). Briefly, IVT is typically performed with a linear or circular DNA template containing a promoter, a pool of ribonucleotide triphosphates, a buffer system that may include DTT and magnesium ions, and an appropriate RNA polymerase (e.g., T3, T7 or SP6 RNA polymerase), DNase I, pyrophosphatase, and / or RNase inhibitor. The exact conditions will vary according to the specific application.
[0154] The mRNA may be synthesized as unmodified or modified mRNA. Typically, mRNAs are modified to enhance stability. Modifications of mRNA can include, for example, modifications of the nucleotides of the RNA. A modified mRNA can thus include, for example, backbone modifications, sugar modifications or base modifications. In some embodiments, antibody encoding mRNAs (e.g., heavy chain and light chain encoding mRNAs) may be synthesized from naturally occurring nucleotides and / or nucleotide analogues (modified nucleotides) including, but not limited to, purines (adenine (A), guanine (G)) or pyrimidines (thymine (T), cytosine (C), uracil (U)), and as modified nucleotides analogues or derivatives of purines and pyrimidines, such as e.g. 1-methyl-adenine, 2-methyl-adenine, 2-methylthio-N-6-isopentenyl-adenine, N6-methyl-adenine, N6-isopentenyl-adenine, 2-thio-cytosine, 3-methyl-cytosine, 4-acetyl-cytosine, 5-methyl-cytosine, 2,6-diaminopurine, 1-methyl-guanine, 2-methyl-guanine, 2,2-dimethyl-guanine, 7-methyl-guanine, inosine, 1-methyl-inosine, pseudouracil (5-uracil), dihydro-uracil, 2-thio-uracil, 4-thio-uracil, 5-carboxymethylaminomethyl-2-thio-uracil, 5-(carboxyhydroxymethyl)-uracil, 5-fluoro-uracil, 5-bromo-uracil, 5- carboxymethylaminomethyl-uracil, 5-methyl-2-thio-uracil, 5-methyl-uracil, N-uracil-5-oxyacetic acid methyl ester, 5-methylaminomethyl-uracil, 5-methoxyaminomethyl-2-thio-uracil, 5’-methoxycarbonylmethyl-uracil, 5-methoxy-uracil, uracil-5-oxyacetic acid methyl ester, uracil-5-oxyacetic acid (v), 1-methyl-pseudouracil, queosine, 13-D-mannosyl-queosine, wybutoxosine, and phosphoramidates, phosphorothioates, peptide nucleotides, methylphosphonates, 7-deazaguanosine, 5-methylcytosine and inosine. The preparation of such analogues is known to a person skilled in the art e.g. from the U.S. Pat. Nos. 4,373,071, 4,401,796, 4,415,732, 4,458,066, 4,500,707, 4,668,777, 4,973,679, 5,047,524, 5,132,418, 5,153,319, 5,262,530 and 5,700,642, the disclosure of which is included here in its full scope by reference.
[0155] In some embodiments, the mRNAs may contain RNA backbone modifications. Typically, a backbone modification is a modification in which the phosphates of the backbone of the nucleotides contained in the RNA are modified chemically. Exemplary backbone modifications typically include, but are not limited to, modifications from the group consisting of methylphosphonates, methylphosphoramidates, phosphoramidates, phosphorothioates (e.g. cytidine 5’-0-(1-thiophosphate)), boranophosphates, positively charged guanidinium groups etc., which means by replacing the phosphodiester linkage by other anionic, cationic or neutral groups.
[0156] In some embodiments, the mRNAs may contain sugar modifications. A typical sugar modification is a chemical modification of the sugar of the nucleotides it contains including, but not limited to, sugar modifications chosen from the group consisting of 2’-deoxy-2’-fluoro-oligoribonucleotide (2’-fluoro-2’-deoxy cytidine 5’-triphosphate, 2’-fluoro-2’-deoxyuridine 5’-triphosphate), 2’-deoxy-2’-deamine-oligoribonucl eotide (2’-amino-2’-deoxycytidine 5’-triphosphate, 2’-amino-2’-deoxyuridine 5’-triphosphate), 2’-O-alkyloligoribonucleotide, 2’-deoxy-2’-C-alkyloligoribonucleotide (2’-O-methylcytidine 5’-triphosphate, 2’-methyluridine 5’-triphosphate), 2’-C-alkyloligoribonucleotide, and isomers thereof (2’-aracytidine 5’-triphosphate, 2’-arauridine 5’-triphosphate), or azidotriphosphates (2’-azido-2’-deoxy cytidine 5’-triphosphate, 2’ -azido-2’ -deoxyuridine 5 ’-triphosphate).
[0157] In some embodiments, the mRNAs may contain modifications of the bases of the nucleotides (base modifications). A modified nucleotide which contains a base modification is also called a base-modified nucleotide. Examples of such base-modified nucleotides include, but are not limited to, 2-amino-6-chloropurine riboside 5’-triphosphate, 2-aminoadenosine 5’-triphosphate, 2-thiocytidine 5’-triphosphate, 2-thiouridine 5’-triphosphate, 4-thiouridine 5’-triphosphate, 5-aminoallylcytidine 5’-triphosphate, 5-aminoallyluridine 5’-triphosphate, 5-bromocytidine 5’-triphosphate, 5-bromouridine 5’-triphosphate, 5-iodocytidine 5’-triphosphate, 5-iodouridine 5’-triphosphate, 5-methylcytidine 5’-triphosphate, 5-methyluridine 5’-triphosphate, 6-azacytidine 5’-triphosphate, 6-azauridine 5’-triphosphate, 6-chloropurine riboside 5’-triphosphate, 7-deazaadenosine 5’-triphosphate, 7-deazaguanosine 5’-triphosphate, 8-azaadenosine 5’-triphosphate, 8-azidoadenosine 5’-triphosphate, benzimidazole riboside 5’-triphosphate, N1 -methyladenosine 5’-triphosphate, N1 -methylguanosine 5’-triphosphate, N6-methyladenosine 5 ’-triphosphate, 06-methylguanosine 5’-triphosphate, pseudouridine 5’-triphosphate, puromycin 5’-triphosphate or xanthosine 5’-triphosphate. In some embodiments, the RNA contains pseudouridine-modified nucleotides.
[0158] In some embodiments, the mRNAs include a 5’ cap structure. A 5’ cap is typically added as follows: first, an RNA terminal phosphatase removes one of the terminal phosphate groups from the 5’ nucleotide, leaving two terminal phosphates; guanosine triphosphate (GTP) is then added to the terminal phosphates via a guanylyl transferase, producing a 5’5’5 triphosphate linkage; and the 7-nitrogen of guanine is then methylated by a methyltransferase. Examples of cap structures include, but are not limited to, m7G(5’)ppp (5’(A,G(5’)ppp(5)A and G(5)ppp(5’)G.
[0159] In some embodiments, the retrotransposon of the present disclosure is delivered by a vector such as a plasmid vector and a viral vector (e.g., adenoviral vector).
[0160] In some embodiments, the target mammalian cell is a human cell. In some embodiments, the human cell is an induced pluripotent stem cell (iPSC). When an mRNA is directly introduced to the target stem cell, in a preferred embodiment, the downstream flanking sequence of the retrotransposon has a length of at least 5 nt, such as 5 to 50 nt, 7 to 30 nt, or 8 to 20 nt.
[0161] In some embodiments, the R2 ORF and the exogenous gene are included in the same retrotransposon polynucleotide. In some embodiments, only the exogenous gene is included in the retrotransposon polynucleotide, while the R2 ORF is delivered separately on a different polynucleotide.
[0162] In some embodiments, the delivery is in vitro. In some embodiments, the delivery is in vivo or ex vivo. In some embodiments, the retrotransposon polynucleotide is delivered by parenteral means, or locally.
[0163] The term “parenteral” as used herein refers to modes of administration which include intravenous, intramuscular, intraperitoneal, intrasternal, subcutaneous and intra-articular injection and infusion.
[0164] Delivery can be systemic or local. In addition, it may be desirable to introduce the retrotransposon polynucleotide of the disclosure into the central nervous system by any suitable route, including intraventricular and intrathecal injection; intraventricular injection may be facilitated by an intraventricular catheter, for example, attached to a reservoir, such as an Ommaya reservoir. Pulmonary administration can also be employed, e.g., by use of an inhaler or nebulizer, and formulation with an aerosolizing agent. EXAMPLES
[0165] The following examples are included to demonstrate specific embodiments of the disclosure. It should be appreciated by those of skill in the art that the techniques disclosed in the examples which follow represent techniques to function well in the practice of the disclosure, and thus can be considered to constitute specific modes for its practice. However, those of skill in the art should, in light of the present disclosure, appreciate that many changes can be made in the specific embodiments which are disclosed and still obtain a like or similar result without departing from the spirit and scope of the disclosure. Example 1: Discovery and Testing of New R2 Retrotransposons
[0166] This example describes the discovery and testing of new R2 retrotransposons from various species.
[0167] The amino acid sequence of the open reading frame (ORF) of known R2 sequences, in particular those of the main functional domains, was used to search for analogs in the GenBank database. The genomic and amino acid sequences of the hits were examined with respect to domains / motif common to R2 retrotransposons, including zinc finger domains, SANT / Myb domains, reverse-transcriptase domain, and endonuclease domains.
[0168] R2 retrotransposons selected based on such sequence analysis (Table 1) were subjected to in vitro retrotransposition activity assessment. For each R2 retrotransposon, the entire sequence of the open reading frame (ORF), its reverse-transcriptase (RT) domain (underlined in the ORF sequence and also separated listed), and the corresponding 5’UTR and 3’UTR sequences are provided.
[0169] The retrotransposition activities of these newly discovered R2 retrotransposons were tested with cultured human cell line, 293T. Cells were grown in Dulbecco’s minimal essential medium (DMEM) supplemented with 10% fetal bovine serum (Gibco) and 1% penicillin / streptomycin (Invitrogen) in 5% CO2 at 37 °C. Cells were grown as adherent cell cultures and passaged every 72 h at a 1:5 dilution (volume of cells: final volume of medium) until confluency was reached, in order to maintain log-phase growth.
[0170] Cells were seeded at 60% confluence in 24-well cluster plates one day before transfection. For transfection, OptiMEM medium (Invitrogen) was pre-warmed to room temperature. Transfection of mRNA into cells was performed with Lipofectamine® MessengerMAX™ (Invitrogen). mRNA Lipofectamine® MessengerMAX™ Reagent (1.5 pL of each) were mixed with 25 pl OptiMEM medium and incubated for 10 min at temperature. 0.5 pg of mRNA was mixed with OptiMEM medium in total volume 25 pL. Then, mixed 25 pL of lipofectamine reagent mixture with 25 pL mRNA mixture and incubated for 5 min at temperature. Mixtures were applied to each well. Helper virus infected the plasmid transfected cells at the same time and continue to incubate for 72 h. Integration of the donor sequence into the human genome was measured with quantitative PCR (qPCR) or or digital PCR (dPCR) in isolated genomic DNA. Table 1. R2 Sequences Name Sequence SEQID NO: (1) R2ApuApu ORF MWQVAQAFFVSVATQTAWADWRTTSVTTNICDQTDKVGLDVEVDVTKRLEFLNSKYGECEYE RPPSDSEQLASLPEVYEVLTSASLTGNDTSPQLEVAEAGLGVIDPVSPDDSMYSFISPTPSP AKEPSEGGTPLIKMPDKNPPCPCCGTRMGKMTELIDHLKRKHGIRKLLFQCARCGKTNEKHH SIACHIPKCTGSSEPATVGGFECEECHKTFETNIGLGQHKRLAHPALRNLERILASRPKETT ARGKHKQCWSEEELELLQKLEKQLEGQKNINKLIGEQIPTKTAKQISDKRRAIREKKCPIRP EGHKRWEAQDVRSSPVRNKSGRLGSLYRKVISGWLSSNKLSILNKIFEKMLLAKENWEHLN DTAMTEFYNILGASTKKQRPGAKQPEARKTRPSGQQKEWMKKRSRKRGNFLRHQRLFHLDRG KLANIILDDVESLTCDIPPDEVHSVFKSRWESTGAYNGLGSFKAFERADNSAFNIMISAKEI SKNIKEISKTAAPGPDKITLRELTKIDPHCNHLRELFNLWLLTGMIPDSVKNCRTVLIAKSA VPERLGDINNWRPITIGSIILRLFSRIITARLAKACPINPRQRGFIRSAGCGENLKLLQLII RHAKSQHQPLGWFVDLAKAFDTVSHAHIISALEQRGVDQHIIALIKNMYHNVTTNIPLKDG HSDSIKIQIGVKQGDPMSPLLFNLAVDPLLCKLQECGEGFQIHSQNITALAFADDLVLLSNS WEGMMKNIEIVETFCNLTGLKTQGEKCHGFYIQPTKDSYKINDCPAWPINGTPLNMIDPGSS EKYLGMNIDPWGISKPELLSKVKNWLHRIDRAPLKPFQKVEILRTYAMPRLIYSADQANVK ITHLEMLDQEIRSAVKQWLHLPPSTCDAILYASNRDGGFGLLRFSKLIPSVQARRLHRLAQS 1 PDEVITTIVRLEGIEKEYEKLWVKAGGRKDKIPSIWDPRTVFRLPNEVGGEEITSEWEAPAP KNIYPKPCWRKDEFNNWTKLASQGKGISNFENDKISNDWLTHYRGIPHRKLLTALQLRANV YCNREFLARGRHDSQDASCRHCQADVESCAHIIGYCPKVQEARIKRHNNICNLLIEEAKNKD WWFQEPNLRDKNNLFKPDMIFVKDKQALWDVTIRYESNPSSLSEAAAGKVQKYKHLTQQV QELTNATHVKFVGFPIGARGKWYSENHDLLTEIGLSKSHQQKLARKMVNWALFSSVEIVHMF ASQARV (1) R2ApuApu RT NCRTVLIAKSAVPERLGDINNWRPITIGSIILRLFSRIITARLAKACPINPRQRGFIRSAGC GENLKLLQLIIRHAKSQHQPLGVVFVDLAKAFDTVSHAHIISALEQRGVDQHIIALIKNMYH NVTTNIPLKDGHSDSIKIQIGVKQGDPMSPLLFNLAVDPLLCKLQECGEGFQIHSQNITALA FADDLVLLSNSWEGMMKNIEIVETFCNLTGLKTQGEKCHGFYIQPTKDSYKINDCPAWPING TPLNMIDPGSSEKYLGMNI 2 (1) R2ApuApu 5'UTR AATCAGGGGGCGTAATTGTGGAATTTTATCTGATCGGGCTTTAGCTTCCCACAACTCCTGTT GAGGATAAGTGGGCGGGAGTAACTATGACTCTCTTAAGACGGGATCATAGTTACTAGCTGGG CTTTGCTGCAGAGGTCCCACCTCCTCGTGGTCCCGCTGGATGCCCTACTGGGTAACCAAGAG GAC CTCTGCCC CAGT GCTGGAGTAGTAGTAGCTGCTACCGCCCTACCGAGT GGAC T C AC CAC CCCTCGGTAGAATTCCCTAAGGTGAAACACAATTGTTGACAGTGTCTGTGCTGTCCAAGGCC TTGCCCACGGGCTGCTGTTGGGCAAAACCGACTCCCTTGGAGGGGGGATCTCGGTAAAGACT AATCCTCAACCGATTTGGACAAA 3 (1) R2ApuApu 3'UTR TGTTAGCGTCGGATTCGACTGTAAGCGTGCGGGTTTCACTGTTTGTTTTATTAAATGTTGCA GGATAGGGGTGGGACAAAAAACTGGGATCTCGTAATGATTACCTCAAACATGACGCATCACA T T GGAC T T GAC GAGGGT GGAC GAGC CAC C T T T AC T T AAC T C GGAAAAGGAACAT AGC C C GC T ATGTTCTCTAAATAGTCACCCTTTTCTTCCAATTAATTCATCCGCACTTCTGCCCCTTGCTC AC AC C GAGC C GT AC GC AAT T C C C AC AGAGT GT A 4 (2) R2AspTig ORF MHRFHRHAEELNEERSARLPTKKLTWSKEEDSSLVRHASRLWAPNLLKKHLLDLLAPLFPGR STESIKKRLQILKWLPPTTPTEASSTSSQDATSSSTQNATSTSNQEATIQDSTPTPSWRDDL LDFAVKNLQEPKLGSDDLRIIASELQSGTISCADAAQLLEDHARHWFPHTWKPSKEKHHSLD PSASKKQVRRANYAAIQRLYHLRRKDAASCVLSGKWRRAHRGPTAKVDGLDEYWSEIFELPS APDHCVTGPSKDKDWSLLGVISAAEVTSALRDMGNSAAGLDRLTPSTLLTWDQPSIAALFNL ILATESVPRHLAKSRVIFLPKSEDPASPSDFRPISIASVLLRALHKILARRITSTLKFSQLQ HAFLKRDGCLDASSLLHAVFRKVHDNRVPVSMVFLDISKAFDSVSVHTLLRVAKSSGLPPPL TNYLDSLYDRPCVQLESRTSICGRGVRQGDPLSPLLFIMTMEVLLQSSIPEIGFDLDGNHIP ABAYADDLVLFAEKPERLQEKINGLFGSLSSAGMTINAKKSMGLTVAKDGKHKTMVLLPHAY MSGSTPIRPMGPSDTTRYLGLEFSWKGKVTPKHTSKLDQMLQEISKAPLKPYQRLDLLKNFA IPKLTHELVLGNAHRNTLKKLDVLVRASVRSWLRLPKDTPLGYLYAHVRDGGLGLPCLHTSI PVLQKNRFAKLLSNPGSIHKAITSQKSFRWQRRIDLPVTIGGHLVQSKKDARAAWLNDLKR SVDGKDLFGDPIDPVSHRWVSHPQRVFPRLHLRGIQLRGGLLATRARNARGRNLDGTPKTCK GLCGQTETINHILQVCDRTHDARCARHNRIVQKLQRFLRKKKIPTWVEPMIPSGHSYIKPDI IATINNELLVIDVSIVSGPRLSESWQLKSSKYGSSTNTTAIQAWHGSPITVRQAPLIISNRG LLFAQSGQALRSIGLTSRDMTDLCLLAIIGSLKCYDSYTRSTQDYKLQRGGQHAGNS 5 (2) R2AspTig RT KSRVIFLPKSEDPASPSDFRPISIASVLLRALHKILARRITSTLKFSQLQHAFLKRDGCLDA SSLLHAVFRKVHDNRVPVSMVFLDISKAFDSVSVHTLLRVAKSSGLPPPLTNYLDSLYDRPC VQLESRTSICGRGVRQGDPLSPLLFIMTMEVLLQSSIPEIGFDLDGNHIPALAYADDLVLFA EKPERLQEKINGLFGSLSSAGMTINAKKSMGLTVAKDGKHKTMVLLPHAYMSGSTPIRPMGP SDTTRYLGLEF 6 (2) R2AspTig 5'UTR GGGTCGTAGTTACATGGCCTGGGCGCCTCCTCGTGGCGACCGCTGGAGAAGATGGGGACGAA TCTCGTCTCCATCCGAGCTAAGATCCAGGCCACCCCCCTCCTCTGGGCTAACCATCCATTGG AGGGGTCTCTCTGCTGGTTACGAT7V?\AC2VA?V^AGA?W7^ATTCGCCTGGTCCCTCCGGACTTC AGGCTAGCAGCAGT^TVACT^ATGT^AGTTGCAGGTGCTCCCGGCGCTCCTGCCCCCCCCTCTGAC AGTTTTGACTGCTCCTGTGGTCGAGTGTTTCCATCT^ / ^AGAGT^AGTCTAGCC 7 (2) R2AspTig 3'UTR TGATCTGCTTTCCCAAGTGGTGACTACCCTGCAAGTTTATTGTCAAAGCGTTAGCCGCCTCG GAGCTCATTACGTTACTATGGCCTGCATTGGGCTCGCCAAAATGTAACGACTGACTCTGATA AT AT AT GAC ACC 8 (3) R2AspTig' ORF MLVTINKKKNSPGPSGLQASSRNNEVAGAPGAPAPPSDSFDCSCGRVFPSKRSLAMHRFHRH AEELNEERSARLPTKKLTWSKEEDSSLVRHASRLWAPNLLKKHLLDLLAPLFPGRSTESIKK RLQILKWLPPTTPTEASSTSSQDATSSSTQKATSTSNQEATIQDSTPTPSWRDDLLDFAVKN LQEPKLGSDDLRIIASELQSGTISCADAAQLLEDHARHWFPHTWKPSKEKHHSLDPSASKKQ VRRANYAAIQRLYHLRRKDAASCVLSGKWRRAHRGPTAKVDGLDEYWSEIFELPSAPDHCVT GPSKDKDWSLLGVISAAEVTSALRDMGNSAAGLDRLTPSTLLTWDQPSIAALFNLILATESV PRHLAKSRVIFLPKSEDPASPSDFRPISIASVLLRALHKILARRITSTLKFSQLQHAFLKRD GCLDASSLLHAVFRKVHDNRVPVSMVFWISKAFDSVSVHTLLRVAKSSGLPPPLTNYLDSL YDRPCVQLE SRTSICGRGVRQGDPLSPLLFIMTMEVLLQSSIPEIGFDLDGNHIPALAYADD LVLFAEKPERLQEKINGLFGSLSSAGMTINAKKSMGLTVAKDGKHKTMVLLPHAYMSGSTPI RPMGPSDTTRYLGLEFSWKGKVTPKHTSKLDQMLQEISKAPLKPYQRLDLLKNFAIPKLTHE 9 LVLGNAHRNTLKKLDVLVRASVRSWLRLPKDTPLGYLYAHVRDGGLGLPCLHTSIPVLQKNR FAKLLSNPGSIHKAITSQKSFRVVQRRIDLPVTIGGHLVQSKKDARAAWLNDLKRSVDGKDL FGDPIDPVSHRWVSHPQRVFPRLHLRGIQLRGGLLATRARNARGRNLDGTPKTCKGLCGQTE TINHILQVCDRTHDARCARHNRIVQKLQRFLRKKKIPTWVEPMIPSGHSYIKPDIIATINNE LLVIDVSIVSGPRLSESWQLKSSKYGSSTNTTAIQAWHGSPITVRQAPLIISNRGLLFAQSG QALRSIGLTSRDMTDLCLLAIIGSLKCYDSYTRSTQDYKLQRGGQHAGNS (3) R2AspTig' RT KSRVIFLPKSEDPASPSDFRPISIASVLLRALHKILARRITSTLKFSQLQHAFLKRDGCLDA SSLLHAVFRKVHDNRVPVSMVFLDISKAFDSVSVHTLLRVAKSSGLPPPLTNYLDSLYDRPC VQLESRTSICGRGVRQGDPLSPLLFIMTMEVLLQSSIPEIGFDLDGNHIPALAYADDLVLFA EKPERLQEKINGLFGSLSSAGMTINAKKSMGLTVAKDGKHKTMVLLPHAYMSGSTPIRPMGP SDTTRYLGLEF 10 (3) R2AspTig' 5'UTR GTCGTAGTTACATGGCCTGGGCGCCTCCTCGTGGCGACCGCTGGAGAAGATGGGGACGAATC TCGTCTCCATCCGAGCTAAGATCCAGGCCACCCCCCTCCTCTGGGCTAACCATCCATTGGAG GGGTCTCT 11 (3) R2AspTig' 3'UTR TGATCTGCTTTCCCAAGTGGTGACTACCCTGCAAGTTTATTGTCAAAGCGTTAGCCGCCTCG GAGCTCATTACGTTACTATGGCCTGCATTGGGCTCGCCAAAATGTAACGACTGACTCTGATA AT AT AT GAC ACC 12 (4) R2ChaBot ORF MASGGANEFRCDCGTLWPSARSLAMHNFHRHTEKVMAERREKQPAKRLRWSAEEEAALHRQA DRLWSEGMLSKDLCLLLTDFFPGRSAEAIKKRLQSTRWIPPGQRPPVSPEGNEESSLAEQFD FAMWSKDLLEEAVGNLQEPRMGAELLSRIARGLLTGEFSKEEGVKRLEDHACQWFPYRWKSS VPRKSGNPQMHSNKKIRRMNYAAIQRMYHRRLKDAATCVLSGQWRTAYQPRPEVEGLNEYWT KIFETRSVEDTGCLRTPTRTLYSLIGRIIPSEVTAALKTMRSSAPGLDRITASELLAWHQPS IASYYNLLLVLEVCPRYLSCSRVAFLPKVPVPSAPDDLRPISITSVLLRAFHKILARRLNDE LHLTSLQFAFLQRDGCLDATTLLHSILRNIHHTRSPGAMLFLDISKAFDTVSHSTIARIITS AGFPIPLIHYICNLYSNSTVQLGEKMIKCGRGVRQGDPLSPLLFILVIEEILLASLPDVGYN FGGQRLGAIAYADDLVLLAEHPQRLQEKFKIFSEALHTTGMVLNPKKSIGLTISRDGKRKAI VWQPHCYNYLGTPIRPLKIDESVKYLGLQFNWKGRINPRHVGKLDEMLGEISAAPLKPYQRI RILTSFLIPKLTHSLVLGLAYRKTLKRADRLVYAAVRSWLRLPKDTALGYFHASVADGGLGI PCLSTTIPLLQRDQFAKLISQTDPLSVIIREQEAFKVVGNIINRPCRINSRWTSKEEARAE WKTSLSQSVDGSELTIPDVDLASHGWLKYPVRVFPRLFLRGIQLRGGVLPTKARSARGNNRV VVDRSCKGLCGTSETLNHVLQSCEITHNARCSRHNKIVQQLEYLLNKIGIKIWVEPIIPSGS SFIKPDLWMKDNQLWVLDVSIVSGMRLRESWNIKIVKYGSTERVNDIVCWFGSPIAVKQLP IIISNRGLCSTFSGSGLRALGLSRRDITDLCLLTVKGSLMCYDLYNRSTRSSGR 13 (4) R2ChaBot RT CSRVAFLPKVPVPSAPDDLRPISITSVLLRAFHKILARRLNDELHLTSLQFAFLQRDGCLDA TTLLHSILRNIHHTRSPGAMLFLDISKAFDTVSHSTIARIITSAGFPIPLIHYICNLYSNST VQLGEKMIKCGRGVRQGDPLSPLLFILVIEEILLASLPDVGYNFGGQRLGAIAYADDLVLLA EHPQRLQEKFKIFSEALHTTGMVLNPKKSIGLTISRDGKRKAIVWQPHCYNYLGTPIRPLKI DESVKYLGLQF 14 (4) R2ChaBot 5'UTR GTTAGGGTTAGGGTTAGGGTTAGGGTTAGGGTTAGGGTTAGGGTTAGGGTTAGGGTTAGGGT TAGGGTTAGGGTTAGGGTTAGGGTTAGGGTTAGGGTTAGGGTTAGGGTTAGGGTTAGGGTTA GGGTTAGGGTTAGGGTTAGGGTTAGGGTTAGGGTTAGGGTTAGGGTTAGGGTTAGGGTTAGG GTTAGGGTTAGGGTTAGGGTTAGGGTTAGGGCGGGAGTAACTATGACTCTCTTAACTTTCTT GTCATAGTTACAGGCCTGGACACCTCCGCGTGGTGCCCGCTGGATAGGGTATGGGATCTTAT ATCCCATGCCTGAACTAAGTTCCAGGCCACCCTCCTCTCGGGAAGACTTAATTACCCGTTAG GAGGTTGCTGCTGTTTTTTTGTTAAATTGATTAATTTATGTCCGGAGCCCTCTGGTTGACCG GTGATACAGCAGGTAAGTGAGGTAAGACAGTTGTCAAGAATCCACA 15 (4) R2ChaBot 3'UTR TTTTCGATCTGGATTCGATGT^ACGACGATTGTCTCCTGTTATGATTTGTVATTATTTTCTTGG AGATGTTGTATTTATT^^TTTGCTAAATTATT^ATTGTATCTTTTTGT^ACATACTCCT^ATAAT AAATGTAAA 16 (5) R2ColStr ORF MRQPLRVDFISVATQTSWAELWAARDNVFGFKSVSDKNEFHLNDPRFLKSMCNKGGGHLNDP GFLKDVSDKNGFIFNDFECLNSQFNFNTLEFLNSKFGLSDLTLCLDKLSVLPEPYEEPAPPP LSDNINRPGNQTSRPHPLQRDRELGNRPPNKAFEAFETLEAPAGESTITLIPSGEPLTPPAN PRGESTSPLYSRGCEPAAALTPIIKIPDRNLACPCCGVQFNNAQGILDHLKRAHGNKKVLFQ CAKCGRTGEKHHSIACHYPKCKGLPTASPPKGWTCEECQASFGTKIGLGQHKRLAHPVTRNN ERIAASRPKEKNNRGKHKQCWTEEEIELLKILDKKFQGSKNINKLIAEHITTKTAKQISDKR RDLNNSVTAKQLEFITETVTETVPIREQPEDLGGQEKNYIKGFYRKILSKSLTSKKKDFFHD LAKKVIKGKDHLSLSKEAIDEYYNLLHRRTAELHANQSRKIREAKITTSSKHSKEWMKKRAR RRGAFLRFQRLFHLNRGKLAGIILDEKESPQCDIPLEEIHRVFKSRWESPGTFKGLADFRSS GLADNTAFESLITAKEIAKNIKEMNTESSPGPDGVKVKDLAKIDPDFTRIAELFNLWLTTGE VPDKVKECRSVLLPKAADPGRLIDINNWRPITIGSAILRLFSRILTARLAKACPINPRQRGF IQSAGCAENLKLLQLIMQNAKKEHHALGWFVDLAKAFDSVNHSHILSVLKQKGVDEHIIAL ITELYRNVTTSIQVKKARTESIGIHIGVKQGDPMSPLLFNLALDPLLCKLENSGYGYQHCDK NITAMAFADDLVLLSSS’WDGMNRNIKILETFCDLTGLKIQGEKCHGFFIKPTKDSYTINDCE 17 AWAINNTPLKLIAPGDSEKYLGLQIDPWSGLAKPELLSKMKKWLDLIDKAPLKPCQKVDILK GYAIPRVIYLADQSNAKVTNLEVLDLTIRNSVKLWLHLPPSTCDALLYARTRDGGLGITRLT ALIPSIQARRLHRIAQSSDEIIRSVARNENIEKEYSKLWVTAGGDKDKIPCIWEPQSVLWS EEGSDLDGGTEWERPRLNVYYPKPCNWRKQEFQKWIKLQSQGRGISNFEGDKISNNWIGNNR SIPQRKIITALQLRANVYPTREFLARGRQDNFNKTCRHCNSEIESTAHIIGFCPSVQEARIK RHNYVCEILIEEARKCDWLVFQEPLIRDECNELFKPDLVFVKDQTARWDVTIRFENKLATL KEAAEEKVNKYKHLEHQIKELTNASIVKFSGFPLGSRGKWFEGNFELLTELGLSASRREKVA RRLSNKALFTSVDIIHMFASSAKRPRDPNE (5) R2ColStr RT ECRSVLLPKAADPGRLIDINNWRPITIGSAILRLFSRILTARLAKACPTNPRQRGFTQSAGC AENLKLLQLIMQNAKKEHHALGVVFVDLAKAFDSVNHSHILSVLKQKGVDEHIIALITELYR NVTTSIQVKKARTESIGIHIGVKQGDPMSPLLFNLALDPLLCKLENSGYGYQHCDKNITAMA FADDLVLLSSSWDGMNRNIKILETFCDLTGLKIQGEKCHGFFIKPTKDSYTINDCEAWAINN TPLKLIAPGDSEKYLGLQI 18 (5) R2ColStr 5'UTR AAGGTAAGTGGGGAGACCTGGCAGCCTAACTCTCCTAGACGCTCTCTGGGGGGGGGTGGACC TGGCAGTCCTGCTTGCTTTCTTTTTGGGGGCTCATAGTTACTAACTGGGCTCAGCCGCAGAG ACCACACCTCCACGTGGTCCCGCTGGATACCCTACCGGGTAACTAAGCTGGTCTCTGCCCCA GTGCCGGGAGTTAAAATCTCCCTTTTTTGCTGTGCGAACTCACCGAACGTACAGCAGTAAAA ACTCGGTGTTACAAAGTTTCTCTGACTGCAAATAAACTTTGCAGTCTCAAGCCCGAGCCCGT GGGAAAACTGGGCGCAGCTACCAGCACCTGAGGGGTGTGCTGATTAGCTATTGTCTTACCCT CAATACCGGACTGACTAGCTATTGTCTCCGCCCGGCCAGACCGGTCCGACAGGAATTCCTGG A 19 (5) R2ColStr 3'UTR ACTGTTAGTATTAAGGTTTTTCTTTTACGTTATTTTGCCCAGTATACTGTATAGCTTTACTG TACTACCCTGTTTTTAAATACCCCCGAATGTTTTGCAGTGTCCCCTTATTTTAATTATGTAT TGTAGACCCTGTAAACCCCCTGTTGTTTATTATAAATTGTTTTATTCCCCAATCAATAAATC CACCCGACTGTGACGGCCAAGCACCACCCGACGGCTGTGAGAGTAGCGATACGGAATCTCGT TCCGGATCCACATGACGTGTCATTTAAAGTTCTGATTGGACAAGTAATAACCGGACTTGCCA CAGGTGGACGGGCCACCTTTACCTAACCCGGAAAAGAGACAGTCTCGTCTGTCTTCGTAA 20 (6) R2CroOre ORF MLTDTWLRPPGLPDPSCPGSCPRVASPKSDAECPKHSCPCGSEFGTKRGLAMHRFHCHPAE VNAERLTTLPTKKLWTQEEMDGLLRHANGAWKEGMLKTQIFTSLMPHFPGRSAEAIKKRLQ SLKWVPARDNPERNSQPLHATSGNVAPATLPTPDPSRVDDQGANIEDPAASWRRALLAAAAD HFKEPKLGAGTLKQITQDLLNGKISSGECRVLMGEHAQHWFPHTWKPSSARPEPKARQWKAR EIRRANYAAVQKLYKLRRRDAAQAVFSGSWRNAYRGRAPQPDKMDQYWAEVFETASATDVTP PGSPSEIYWSVVSKITPSEVADALKGMRNSAPGLDRITAEELLTWDHPSLAAYYNLMLAAGG PPEHLACSRVTFIPKVENPQTPGDYRPISVASTVLRAFHKILAWRLRDNLQLSPFQHGFLQR DGCLEATALLHTILRKVHNSRKSCAMLFLDVAKAFDTVSHQTLFRVAVELGLPPPLVNYLKC LYSRSTVRLADKATKCGRGVRQGDPLSPLLFIMVMDDIVRKTLPEVGFDLDGQRVDSLAYAD DLVLLAEKSPRLQDKLHLLSEALRKAGMSLNARKSRGLTITKVSKRKQMVITPTTYECEGEP IKPMGTDDSVRYLGLHFNWKGRTVPKHTGKLDSLLKELTKAPLKPYQRLQLLKFHAVPKFTH ELVLGHAHRNTVKKLDCLTRAAVRKWLRLPQDTPLGYLHANVKDGGLGIPCFSTSIPLLQKK RFEKIATNPATIFQIMQRQDSFRTQGRRLDKPCRLNSTVVTSKTEVREEWGNMLSNSVDGRE LRHPEVDKASHEWLLRPDRVFPRLHMRGIQLRGGLLPTKARSGRGNNRQVTSKTCRGACQNV ETLNHILQVCDVTHDARCARHNRVLHRLERLLHKKGLRTTLEPVIPAGSSFIKPDLIIETDT QTYVLDVSVVAGYRMTESWDIKVEKYGRPDRVEAIRKWAAIPATKRVEHLPVIVSNRGLCYQ PSGDGLRALGLTSRDISDLCLLAISGSLRCYDLYMRGTRAV 21 (6) R2CroOre RT CSRVTFIPKVENPQTPGDYRPISVASTVLRAFHKILAWRLRDNLQLSPFQHGFLQRDGCLEA TALLHTILRKVHNSRKSCAMLFLDVAKAFDTVSHQTLFRVAVELGLPPPLVNYLKCLYSRST VRLADKATKCGRGVRQGDPLSPLLFIMVMDDIVRKTLPEVGFDLDGQRVDSLAYADDLVLLA EKSPRLQDKLHLLSEALRKAGMSLNARKSRGLTITKVSKRKQMVITPTTYECEGEPIKPMGT DDSVRYLGLHF 22 (6) R2CroOre 5'UTR CGACCATTTGGTGTTGATATTGATACTGGCGACTGGCTAGTTGGTGTTGGTTGAAAGCGCTG GCGAGGTTGAGCTGATAATTGGTTGCACGGGTTGGGCACCTCCTAGTGGTGACCGCTGGATA GGGCTTCGGCCTGAGCCT^AGATCCAACCCACCCTCCGTTGCTGGCAGACCCCAGTTYACTGAG ATTAZV^CAGCTGGT 23 (6) R2CroOre 3'UTR GACTACCGAGCGCCACCGGAGGGGACCCAGAGGACCGTCTCGGTGATTAGGCGGTGACCGCC CTGGCCTCTACCTGAAATAGCGATCAAATCGCCTTAGAGGGCCTGATTTGGGGGGTTGGGCA GACACTCTGTGTCATTACTGCCCTTTACCTTTCCACTTCTTGCCTGTCTAATAATAAATG 24 (7) R2HemCom ORF WRLAQACFVSVATQTTWADWHTNLVTTNISDQLKPVELEVDVRGLEFVNSKIGEIDGYHLP TESEQLASLPEVYEVLTLTSLTGNDTSPQSEVLEAGAEVTDPVSPDDSILSFISPTPSPAKD LTDESTPIVKIPDKNPSCPCCGTRMGKITSLIDHLKRTHGERKILFQCARCGKTNEKHHSIA CHFPKCTDKVASATVGGFECEECHKTFETKIGLGQHKRLVHPAIRNIERTLASRPKETSARG KHRQCWSEEEVELLQKLENQFEGHKNINKLIAEQIPTKTAKQISDKRRALREKKDSKQSESP EWGEAQEIRPSPVRPRGGRLGSHYRKVISDWLTSNKLPILRKIFEKVMLAKGDLRTLVDLAI KEHYKHLVGSSVERRKGHGSRQHEARKIHPSGQPKEWMKRRCRKRGNFLKYQRLFHLDRGKL 25 ADIILDDVESLTCDIPPDEVHEVFKSRWGSTGTFTGLGPFQAFERAGNSAFDIMISAKEISK NIKEMNKNAAPGPDRITLKHLIKLDPHCYQLKELFNLWLLTGMIPDWKDCRTILIAKSAIP ERLKDINNWRPITIGSIVLRLFSRIRTSRLTKACPINPRQRGFIRSPGCAENLKLLQLMIRH AKS HHLPLGWFVDLAKAFDTVS HDH11S ALRQRGVDDH11 AL IENMYQKVTTKIHLKDGQ S DSIKIQIGVKQGDPMSPLLFNLAVDPLLCKLQESGNGFLIHSKTITAMAFADDLLLLSDSWE GMMKNIKIVETFCNLTGLKTQGEKCHGFYIQPTKDSYKINDCPAWTINGTPLNMIDPGSSEK YLGMCIDPWVGISKPELLSKVKGWLQRIGKAPLKPFQKVEILKVYAMPRLIYSADQADVKIS CLEMLDLEIRSTVKQWLHLPPSTCDAILYSSTRDGGFGLTRFSKLIPSVQARRLHRLAQSPD EVITTIVRSEGIESEYEKLWVRAGGRKEKIPSIWDPRTVIKLTSVAGGEELTSEWEVSAPKN IYPKPCNWRKEEFNNWTKLVXQGKGISNFENDKISNDWLIHYRGIPHRKLLTALQLRANVYC TREFLARGRHGSQNTSCRHCQAEIESCAHXIGYCPKVQDARIKRHNGICDLLIEEAKTKDWI VYQEPNLRADNNLFKPDLILVKDKQALVIDVTVRYESNPSSLSEAAAEKAQKYQHLTQQIQD LTNATNVKYVGFPVGARGKWYLGNYDVLSEIGLSKSHQTKIARRIVNRALFTSVEIVHMFAS KARV (7) R2HemCom RT DCRTILIAKSAIPERLKDINNWRPITIGSIVLRLFSRIRTSRLTKACPINPRQRGFIRSPGC AENLKLLQLMIRHAKSHHLPLGVVFVDLAKAFDTVSHDHIISALRQRGVDDHIIALIENMYQ KVTTKIHLKDGQSDSIKIQIGVKQGDPMSPLLFNLAVDPLLCKLQESGNGFLIHSKTITAMA FADDLLLLSDSWEGMMKNIKIVETFCNLTGLKTQGEKCHGFYIQPTKDSYKINDCPAWTING TPLNMIDPGSSEKYLGMCI 26 (7) R2HemCom 5'UTR ACGGGATCATAGTTACTGACTGGGCTCAGCTGCAGAGGTCCCACCTCCTCGTGGTCCCGCCG GATGCCCTCGTGGGTAACCGAGAGGACCTCTGCCCCAGTGTTGGAGTGAGCAGTAGCTGCTA CCGCCCTATCGAGTGGACTCACCACCCGCTCGGTAGTACTTTTTGAAAGGTGAAACAAATTC CCGACAGCATATCTGCTGTCCAAGGCCTGGCCCACGGGCTACGTTGGGCAAAACCGATTGCC TTGAGGGGGGCTTTCGGTGTAGACTTATCCTCAACCTGAATTGACAAA 27 (7) R2HemCom 3'UTR ATTGCGTCGGGTTAAACTGTAAGCGTGCGGGTTCACTGAATAAATGTTATATTGGATAAGGG TGGGACAAAAATTGGGATTCTCGTAATGATTACCTAAACCATGACGCGTCACACCGGACTGG AC T AAT C AGGT GGAC GAGC C AC C T TAT T T AAC T C GGAAAAGGAAC AT AT C T TAC GT T C GAT A AA 28 (8) R2MelGeo ORF MAKIPDPFLGGGVWGPPVRLSRVSVGTQTSPSDWVDLVSRALPRTKCISRGVDLVSQNYLTS KTTNLAENELDSLVNFYFEMYRSDLHEHVHEGVRFSVDWEVLDGLPEVYEQLAPQPCMGENL DASPPRDSEPFVLGEGSGKEVREGTPEALPPVPGEHGGQSPDKIVKVTVPDKNPPCPCCGTR VNSVLSLIEHLKGSHGKKKVCFRCAKCGKENINYHSVICHFPKCRGPVIEKAPAGDWICEVC GRDFTTKIGLGQHKRLAHPLIRNKERIVASQPKETSNRGAHKRCWTKEEEELLIKLVAQFEG NKNINKLIAEHITTKTAKQISDKRRLLPKKTTDEADKELGMRLRSRRWGTEPGSSQQAQAE AENNGPGKNHLPRRPAAGGETMEKIRPTDKDNGHQETSGQQREGQLQAHYHEKIKESLSAGA INNFPRAFKQLMDGQEMQTMINQAAQDCFGCLESISQIRTATRGKKEKVTHEKQPKKPFQKW MKTRAIKKGNYLRFQRLFHLDRGKLAKIILDDIECLSCDIPPSEIYSVFKARWETPGNFAGL GDFEIKGKADNSAFRDLITAKEIERNVQEMSKGSAPGPDGITLGDIRKMDPGYSRTAELFNL WLTSGEIPDMVRGCRTVLIPKSTKPERLKDINNWRPITIGSILLRLFSRIVTARMSKACPLN PRQRGFIRAAGCSENLKLLQTIIRTAKSEHRPLGWFVDIAKAFDTVSHQHIINALQQRGVD PHIIGLVNNMYKDISTYVTTKRNTHTDKIQIRVGVKQGDPLSPLLFNLAMDPLLCKLEEQGK GFHRGQRSITAMAFADDLVLLSDSWENMKTNIKILETFCDLTGLKTQGEKCYGFYIKPTKDS YTVNNCAAWTINGTPLNMINPGESEKYLGLQFDPWTGIAKTNLTTKLDFWLERIDQAPLKPL QKLDILKTYTIPRLTYLADHTEMKAGALEALDQKIRTAVKDWLHLPLSTCDAILYSSTKDGG LGVTKLAGLIPSVQARRLHRIAQSSDETMKEFLEKHQMEQLYKKLWIQAGGESEKMPSIWEA LPATVPSNSADTTSEWEAPTMKTKFPKPCDWRRNEFEKWTKLVSQGRGIKSFEGDKISNDWL QYYRRIPHRKLLTALQLRANVYPTREFLSRGREENYIKACRHCKADNETCAHIIGCCPVTQD ARIKRHNYICDVLTEEAKKKDWVVFKEPHIRDTIKELYKPDLIFVKDGRAFWDVTVRYEAS KTSLEEAAAEKVNKYKHLGSEVRRLTNAKDVVFLGFPLGARGKWYEGNFELLDTLGLSKSRQ VRVAKTLSTTALLSSVDIVHMFASRARRIHDGG 29 (8) R2MelGeo RT GCRTVLIPKSTKPERLKDINNWRPITIGSILLRLFSRIVTARMSKACPLNPRQRGFIRAAGC SENLKLLQTIIRTAKSEHRPLGVVFVDIAKAFDTVSHQHIINALQQRGVDPHIIGLVNNMYK DISTYVTTKRNTHTDKIQIRVGVKQGDPLSPLLFNLAMDPLLCKLEEQGKGFHRGQRSITAM AFADDLVLLSDSWENMKTNIKILETFCDLTGLKTQGEKCYGFYIKPTKDSYTVNNCAAWTIN GTPLNMINPGESEKYLGLQF 30 (8) R2MelGeo 5'UTR CGCCGCGCGAGCGGCGGCGGGTGTTACAGCCCCCGGGCAGCAGGTCTCGCCGAATCCCGGGG CCGAGGGAGAGGACCGCCGCCGCGCCCTCCTCCCCCCCCGTCGGCGGCGCCGTGGCGGGGGG CGTCGCTGCGGCGGCGCCCCCGCAGCGCGGCGTTTCGCGCGGGGGTGCGGGGGCCGGGCCCG CCGGCCCCCGGCGCCGCTGTCAACCGGGGCGGACTGCGCTCAGTGCGCCCCGACCGCGCGGC GCCGCCGGGCCGGGCTCCCGAGCTGGGTCTTTCTCTGCGCTGCGTTCGCGCGGGGTTGCGGG GGCCGGTCCCGCCGGCTCCCGGCGCCGCGGTCGGCCGAGGCTTGCTGCGCTCGGTTGGCCCC GGCGGAGCGGCGTTGCCGGTCGGGGATCGCGGGCTGGGTCGATCTCTGCGCGGCGTTTTGCG CGGGGGTTGCGGGGGCCGCTCCTGCCGGCCCCCGGCGCCGCTGTCGGCCGGGGCCGGCTTCG 31 CTCGGTTCGCCCCGGCGGCGCGGCGTTGCCGGTCCGGGATCGCGGGCTAAATCGATCTTAGC CGCAGGTAGGGAGCCGTTGGGATTCACCAGCCCGACGAACTCCTATAAAATTCGGTGAAACA AATTCCTCGGTAAAAGCCGCGTGGCTTATTGCCTTAAACCTGGCCCCTTCGGTTTCAGACAG GGGCAAAAAGAGTTCAGAATCACTCCGTTTG (8) R2MelGeo 3'UTR AGAATTATTTACTTTTTTTTTTTTTTCTGTTTTAAGTTGTATTAATTATTTTTATTTTGTAT TTGTTTATTTAACCTTTTTGTGTTTTTGTAGTTTGTTGCTTATTGCTTTTGTATGTTTTGTT TCATTTCCCCTTTATATTTTAATAAATTAGACGGTAGCTAGGTTCGTATGGCAGCCACAAGC CAGTTAGGTAGCTCATAGTGAGTAGGGACAGAAAACTTTTTTCATAACGCGTCATTTAACAT CTGATTAGGACCAAGTTACCGGATTTGGACCAATTTACCGGATTTGTCCAAGGTGGACGGGC C AC C T T T AC T T AAC C C GGAAAGGGAAC AT AT AT TAT TAT AT GT GT T C GAAATA 32 (9) R2PeCa ORF MEALSCALLSPLRRALTLLDTKIIPWGRCIFRPLEPLARYRAKVSTVATQTECPNTTTSAVQ SVIGTSQTLSTLNKTNHNCAVETHAVKPFPILTLEIVNSAFKLTGKSSIPLQPNIPIVSSTT TEMEGDGGSSEMLLENNERPPMTSTTTEENCGTENQEKFLVMLPNDDPECPVCGDHVGKPTA LSIHMKRVHGNKVVEYQCLLCGKQESRVHSIICHIPKCKGPETQEPEGDWPCPACEKQFRTK SGLSQHKRSAHPAIRNAERIEACQPKPNSQRGKHKSCWTDEEVTLLKDLETLYLGHRSINKM IADDMKTKTAKQVGEKRRLLGTSKKNNTAIVTPEPGTQKNTLEAQPLKPKAKTGLKNAYKRE IEKYLQTLGHLNGNMAQKNYPDFANEIFRAWIAEDPELNDQIEQTSSSVLSTFLSSTPRLTK RGKKKTESTKSGKEKAWMRKRAVERGTYLRHQQLFDRDRCKLASIILDGTERLQCKIPPDEV LRVYKDKWETCTPFEGLGQFTSYGEADNSAFDLLISRKEWKNMKEMTTNSSPGPDGITMSD LLGEDPEGEKLAGLFNMWLVTGFIPTGVKECKSILIPKTMEPEALKELGNWRPITIGSIVLR LFSRILTTRLAKACPMNERQRGFIAAPGCSENLKVLHLLTRDAKRSKKPLGWFVDIAKAFD SVSHDHIMWVLRERNWQHMVNIIKDSYKNVKTRMELDKEFTEQIAINVGVKQGDPMSPLLF NLAWPLISKLENAGMGYLHGDKKITALAFADDLVMLSDSWDGMKTNIEILEAFCKLSGLKV QARKCHGFFLSPTHDSFTINNCEAWKIATDNLNMIAPGESEKYLGLKVDPWIGFSKPALQNK LDTWLERITRAPLKPPQKLEILNTFTIPRLIYLADHTDYKKTMLASLDHSIRRAVKEWLHLP ADTCDNFFYSRARDGGLGVARLASLIPSIQARRLHRIAHSQDEIIRYVALTNGINEDFQKLW VAAGGDEKKIPVITDPVYIDYKLPQGILEQLTEWEKPRPKAMYPMPCSWRENEFSRWKTLHC QGSGIEHFKNDPISNHWIRNNRGFPARHYILALKMRSNVYPTREYQGRGKNNAPVSCRHCPA KYESLSHILGQCPAVQGARIRRHNKLCELLKREAKKQKWTVYQEPQLRTEDNELRKPDLVFV KDKKALVVDVTVRFEYKEKVFTDAAAEKTQHYESLTPQIRKLTGADEVEYYGFPLGARGKWP EISEQVLTALGLTDSEQRRAARFFSRRTLLYSVDVLNTFTSIGKNKPDFVNKDLAKGGDRWE SCND 33 (9) R2PeCa RT ECKSILIPKTMEPEALKELGNWRPITIGSIVLRLFSRILTTRLAKACPMNERQRGFIAAPGC SENLKVLHLLTRDAKRSKKPLGVVFVDIAKAFDSVSHDHIMWVLRERNLDQHMVNIIKDSYK NVKTRMELDKEFTEQIAINVGVKQGDPMSPLLFNLALDPLISKLENAGMGYLHGDKKITALA FADDLVMLSDSWDGMKTNIEILEAFCKLSGLKVQARKCHGFFLSPTHDSFTINNCEAWKIAT DNLNMIAPGESEKYLGLKV 34 (9) R2PeCa 5'UTR CGGCTGTGTCAAGAGTCTAGTTGCTAGGGCGCAGCTCTGAGACCTCAACCTCCTCGTGGTCC CGCTGGACTACTCCCTGGTGCCTACTGATGCCTAGGAGGGAGATGACTAACTGAGGCTCAAC TGCAGAGTAATACTCCCGACCCTACTGTCCTGGTTTGCCGGCCAGGTAGTAGTATCAATACG GTGAAAAGCAAAGATA 35 (9) R2PeCa 3'UTR ATTATCATGACCGCGATCACCTGATATGACATGTGGGTTGGACAGGCCACCCGGGGTACCCT GTACTCCGAATAACCTGAAAAAGAAACCTGCAAGGGTTTGGTAAA 36 (10) R2CarCar ORF MMAAL AS AQIS P RRGAT S T GL P S T GLNMEIV PWGRCIFR P F E P L AR YRVQV S S VAT Q T E S PM STDGERHPSLGSSQTITTAGEVYPISGPSQRITTAGAISSVTVAQTEAEDMLPALPLEFLNS VFGETVRPDTSPGPCVPTTPTSEKERDAEGSESLVDDRNDTIGVSPTTSTVAVTDGESETRV QGKVLVRLPNDNPTCPFCGDHVGKPTALQVHLKRHHGGKDVEFQCSLCDKIDPKAHSILCHI PKCKGLTSQEPAGDWECEVCAKRFGTKSGLSQHKRRAHPWRNAERIQASQPKPNSQRGKHK SCWSAEEELLLIDFDKMYSGEKCINKLIAEAMKTKTAKQISDKRRLLNLSSKTKSECADPGP GANTHCLEVRSDEPPTITGLESMYMREVKKRLRDQSKGPQHLGLAPFESEILSAWVRGDPNV RSLVETTSIDVLSSFLAPEHETEGKGKKTAQKPKSGKNKSWMKKRAAKKSTYRRYQHLFAND RCKLASIILDGTERLQCQIPLEEVFRAYKDKWETRTPFEGLGQFKSHATADNSAFDLFISAK EVLKNIKEMNMKTAPGPDQVSLRDLVRVDPEGDTLAGLFNAWLVTGVIPDGIKECRSLLIPK TMDPEALKDLGNWRPLTIGSIVLRLFSRILTNRLAKACPLNARQRGFIAAPGCSENLKVLHL ITKQAKKEKKPLGWFIDIAKAFDSVSHDHIMWVLRERGWQHMINIISDSYRNVHTRMEVG KELTPPIAIDVGVKQGDPMSPLLFNLALDPLISTLEKTGKGFPVDAQRVTALAFADDLVMLS DSWEGMNANIQILESFCKLSGLKVQARKCHGFLLSPTHDSFTVNNCEAWKIGCDSLNMIAPG ESEKYLGLKVDPWIGFSKPALSDKLDTWLERINRAPLKPSQKLEMLNTFTVPRVIYLADHTD CKKALLSSLDDKIRRAVKEWLHLPSDTCNNFMYARSRDGGLGVTKLASLIPSIQARRLHRVA NSKDWAIRYIALANDIEDEYKKLWLAAGGDQKAMPAITEPVWDHKLPEHVLEILNEWERPA PKAVYPNPCNWRDAEFANWENLPCQGSGVSHFGNDPISNDWLKHHPGFSERQFLTALKLRAN VYPTREYLGRGKNNHNVQCRHCHASYESLSHILGQCPAVQSARILRHNKLCGILAREARKLK WVTYQEPHLHTAKNELRKPDLVFVKDGTALVVDVTVRFEYKEKTFSDAAAEKVRHYASIjTTE 37 VRKLTGATKVKFFGFPLGARGKWPKINEQVLSALGLSESAQGRAAKLFSRRALLYSTDILNT FAGIGKGLLKPADAKPEGTPRRHVGIS (10) R2CarCar RT ECRSLLIPKTMDPEALKDLGNWRPLTIGSIVLRLFSRILTNRLAKACPLNARQRGFIAAPGC SENLKVLHLITKQAKKEKKPLGVVFIDIAKAFDSVSHDHIMWVLRERGLDQHMINIISDSYR NVHTRMEVGKELTPPIAIDVGVKQGDPMSPLLFNLALDPLISTLEKTGKGFPVDAQRVTALA FADDLVMLSDSWEGMNANIQILESFCKLSGLKVQARKCHGFLLSPTHDSFTVNNCEAWKIGC DSLNMIAPGESEKYLGLKV 38 (10) R2CarCar 5'UTR GGCTGTGTCAAGAGCGTGGTTGCTGGGCCGCAGTATTGAGACCTCAACCTCCTCGTGGTCCC GCTGGACGACTCTCATGGGAACCTCAATATCGGGAGTTGACTGACTGAGGCTCAGCTGCTTT CCTCCCTGCCCTACTGTCCTGGTACACCGGCTAGGCAGTAGAACGCTACGGTGAAAAACACA A 39 (10) R2CarCar 3'UTR TGATTACATCAAAAACTAATTCATGACCGCGATCACTGGACAGGACAAACTGGGTTGGACGG GCCACCCGGGGTTCGGAACACCCCAAATAACCCGAAAAAGAAACCCGCGTGGGTTTG 40 (11) R2PhrBla ORF MGCYSLCSEECPYFLARKESGVPTSLQWEIKGYGCDKILIRLNGRSTAGCQTSPPGTPKRVT GQGREKPERPAGGGAPILVFEGLRADKEEKRSERQKQTENLGTEVGPTRPEPGADKVQEERA DKVQKEQRADKVTQEGEGKQKRERKLDKDEPTIWLPDNKPECPYCKEWGKPTALQKHLTGV HGNQAVTFGCMKCQRKDPRVHAILVHIPKCKGPNIPDARQAQNKHRCEDCGNQYDTQSGLSQ HTRHKHPETRNKQRIEEKEKEKGGKRGTHKSCWTQEETEQLALLWEKYEGHANINKLIQQEL HTKTAKQIGEKRRNILEKRNNKPEIGEEIPKTKTQSINRQTEKEGLANKFKQTAITLIQEHR IKNESIARALHTWLQENNNTRQTVEKATEEILNNFPRTAGIHNIPKRKKTKKPRGPYRGKWR QKRRIQKLTYKQLQELYDKDRAAAAAYILDGEKKTNCDLPIQEVYQTYKDKWETKTEFKGLQ NFHPWGGTNNDILSNLITGEEVKEHLQAMCNKTAAGPDNISVKDLKQVLHVEQKLAELFNLW LITGQIPNTVKKSRSILIPKTSDETEKKKVGNWRPLTISSWLRLFSKIMTSRITKACPLNN RQRGFIAASGCSENLWLLHNIIKRAKDKKKELGWLVDIAKAFDTVSHDHIRWVLRERGMDK hiiqlimsaydnattsiklkegntpdihirsgvkqgdplspllfnbamdpliteleteghgv EDENWTITTLAFADDIAVMSD SCKEMKQNLQIIEAFCNLTGLKVQTTKSYGFALQPTKD SY I VNNIKPWTIKDQPIQMVQPAHTTRYLGIQVGPWKGMEKPNMIADTKKWLQNITKAPLKPTQK LEILRTYTIPRLIYHNEQTGTGKTKLKELDNLIRAGIKSWLHLAHDTCTNLIYTKTKDGGLG ITRLETTLPHQRCNTLLKIINSPDLTTRTIARALGIEEQFSKWWKKAGGSEDNKPKIYPQPQ NTTQKPTEKEEIPVTTKIQPTHKKKEAEEWAKLPCQGGAVENFINDSISNDWIRYKKDMTEK EFITAIKLRTNTYPTREFLARGKENYERKCRKCPAKYESLSHILGQCPGLQNARIWRHNAIG KLLANQAKKKKWTVHQEPHLRNKDNQLRKPDYIFTKERTAMWDITVRWEGKMGGLEEAAQE KIKYYEELRDTIQKEWGVKDISFHGFVCGARGKWPDQNFGILTKLGIESHRLDGLAKLFSRR TVQYSCRMLHTFERDKKNQTGHVDC 41 (11) R2PhrBla RT KSRSILIPKTSDETEKKKVGNWRPLTISSWLRLFSKIMTSRITKACPLNNRQRGFIAASGC SENLWLLHNIIKRAKDKKKELGVVLVDIAKAFDTVSHDHIRWVLRERGMDKHIIQLIMSAYD NATTSIKLKEGNTPDIHIRSGVKQGDPLSPLLFNLAMDPLITELETEGHGVEDENWTITTLA FADDIAVMSDSCKEMKQNLQIIEAFCNLTGLKVQTTKSYGFALQPTKDSYIVNNIKPWTIKD Q PIQMVQ PART TRYL GIQV 42 (11) R2PhrBla 5'UTR GTTGCTGGTTGGTGCCGATAGAGATCCCTCCGCCTCCTCGTGGCCCCGCCGTAAACGAGTGT ATCACTCGGCCAAGAGAGGGATCGCGCCATACCACCCAAACTATTACC 43 (11) R2PhrBla 3'UTR GTGTTAGTTTGTACACCTTGTTAGTTTGTACACTTTGTTGTTGTTGTTTGTTTGATGTTATT T AAC TAT T TAT T CAT T AAAAAC C GGAC AT GGGAT C T C GT AAT GAT T AC CGCCCTGCCCTCCA ACCTAAACACCTGAGGTGGAGGCTGGGATCATGCAACTCACCCTGACTTGACCCTGACCTTA AAAGATGGATGGGCCATCGCGGGGGTTGGTCTCCCCGCAACAACTCAAAAACGAACTGGCGC GAGTCAGTTTC 44 (12) R2PoExORF MEALTVALLSPPRRALNLLDKKIVPWGRCIFRPSEPLARYRAKVCTVATQTECPDTTISEVQ CTRTSQTTNIKDKYGYSYVAEKRNMKPFVVQTNEILNSIYNIKDVLLTPRRREDRLSRLWLE ESMGFDEDEGVYESSPSQETSISEGTPTLHEPAKYWSLPNDDPECPVCGDHIGKPTALSIH LKRTHGDKEVEYLCLLCGKSEQRVHSILCHIPKCKGETTTEPEGDWPCPECEKQFQSKSGLS QHKRSAHPALRNAERIQASQPKSDSQRGNHKRCWTDEEVALLLELEKTYLGHKHVNKMIATE IKTKTAKQVGEKRRLLAQSKKKVTVENTNPGPGAERHSNEKGNFKLKETPLSTLEVRPVQPA SKLGLNGAYKRKLKVYLENQKKMKQDNGFPDFAKDIFSAWVKGDHNIQEMVEQTSSDILSNF RPTLPKPKRTERQNNEKGNFKLKEAKSWMRKRAVKRGTFLRYQHLFDRDRCKLASIILDDTE RLKCEVSPDEILKVYKDKWETRTPFNGLGHFTSHGKIDNSAFELLISAKEVIKNVKEMNKKS APGPDGLTIEDLLGEDPEGERLAGLFNIWLVTGYIPNKIKDCRSILIPKTMDPVALRELGNW RPITIGSIVLRLYSRILTTRLAKACPLNARQRGFIATPGCSENLKTLHLLTRDAKRSKKPLG WFVDIAKAFDSVSHDHIMWVLRERGLDQHMAKIIADSYTNVHTRIEIDNKSTEPISLNVGV KQGDPMSPLLFNLALDPLISQLETTGCGFSHGNKTITALAFADDLVMLSESWGMTKNIEIL EAFCSLSGLKVQAKKCHGFFLSPTHDSYTVNNCKPWQISDDALNMITPGESEKYLGLRVDPW IGFSKPALSDKLDNWLQRITRAPLKPPQKLEILNTFTIPRLIYLADHTDIKKTMLSSLDKNI RRAVKAWLHLPADACDNFLYSRTRDGGLGVARLSSLIPSIQARRLHRIAHSQDETIRSIALA 45 NGITDDYHKLWITAGGDENKIPVITAPVYIDYKLPQGVLDELTEWEKPAPKAIYPIPCSWRE AELSEWKTKQCQGSGIQHFKNDPISNTWLRNQRGFPARHYITALKLRSNVYPSREYQGRGNK NMNVNCRHCPAKYESLSHILGQCPAVQGARIQRHNKLCNILKQRARKLKWTIYQEPQLRTAE NELRKPDFIFVKDQKALWDVTVRFEYKDKVFQDAADEKIQHYCSLTPQIKDLTGAEEVEYF GFPLGARGKWPEINYKVLTALGLSDTEQGRTAKFFSRRTLLYSIDVINTFASLGKNKPSTVN LYPVNKDHNQEGAAGKSCND (12) R2PoExRT DCRSILIPKTMDPVALRELGNWRPITIGSIVLRLYSRILTTRLAKACPLNARQRGFIATPGC SENLKTLHLLTRDAKRSKKPLGVVFVDIAKAFDSVSHDHIMWVLRERGLDQHMAKIIADSYT NVHTRIEIDNKSTEPISLNVGVKQGDPMSPLLFNLALDPLISQLETTGCGFSHGNKTITALA FADDLVMLSESWDGMTKNIEILEAFCSLSGLKVQAKKCHGFFLSPTHDSYTVNNCKPWQISD DALNMITPGESEKYLGLRV 46 (12) R2PoEx 5'UTR TAGGCTGTGTCAAGAGTCGAGTTACTGGGGCGCAGCTCTGAGACCTCAACCTCCTCGTGGTC CCGCTGGACTACTCCCCTGGACCTTCCCATGTCCAGGAGGGAGCTGACCAACTGAGGCTCAA CTGCACGTGTGTTTCCCGCCCTACTACCTTGGTATGCCGGCCAGGTGGTAGTATCAATACGG T GAAAAACAAACA 47 (12) R2PoEx 3'UTR ATTATCATGACCGCGATCACCAGATTGACGTAGGTTGGACGGGCCACCTGGGGTACCAGTTA CTCCGAATAACCCGTAAAAGAAACCCGCAAGGGTTTGTTAAA 48 (13) R2PufMau ORF MIDKMELLMRFAFVSVGTQTSLSDLQDNVVKETITDHGKLVEVEMNWKGLEFINSEIDELER YHPSTWTDRLAILPEVYEIPTSPNLEGTTNSPCLREVESEEEEEPSSPGNMAQFSPLPLTPT PGSEVDPPQVDTPWKVPDNNPSCPCCGNRMGKVSGLIEHLKRVHGRKKILFQCARCGRTNV KHHSIACHFPKCKGAIEIAPTEGWICGECQRVFESKIGLGQHKRLAHPVIRNMERIIASQPK ENSARGAHRQCWTEEEVELLRKLVKQYEGSKNINKLIAEHIPSKTSKQISDKRRGLHKSPVK NKGKDLEWRQHLEEEEHLNDIGSHEEEGLKSHYQRMINKWITSEKLPILRGSFTKVLEGKEK PSTIIDEAIEDCYSCLFKKSGELEVSQDPNHQVTRKTPSSKPRKKWMKKRAKKKGQFLRFQR LFYRDRCKLAGITLDDVESLKCGTPLDEVHKVFKSRWESPGTFRGLGAFRTLGRADNSAFEA MITAKEISKNIKEMSKNAAPGPDGVNLRDLINIDPNCDQLMELFNLWLVTGTIPDWRECRT VLISKS AAPERRNDINNWRPITIGS TVLRLF SRILTARLTKACPINPRQRGFIKS AGCAENL KLLQLLIRNAKKEHRPLGWFVDLAKAFDTVSHSHIIAALKQKGVDEHIIALISNLYYNINT YIDLKKEKSDPIGIQIGVKQGDPMSPILFNLSIDPLLCKLEEDGSGFQHCAKKITAMAFADD LVLLSGSWEGMQKNIEILEVFCELTGLKTQGEKCHGFYIQPTKDSYTINDCPPWTINGTPLN LIEPGSSEKYLGLQIDPWVGTSKPELMKKIEDWLQRTGKAALKPFQKVDTLKGYTTPRLTYL ADQADVKITYLETLDLAIRSAVKEWLHLPPSTCDAILYSSTRDGGLGITRLSGLIPSVQARR LHRIAQSSDELTKAVAREEGIEKEFEKLWIAAGGDKEKIPSIWDPRTVIIISELNPEEQVSE WEVPSPKTIFPRPCDWRKQEFSNWTKLLSQGRGISNFERDKISNNWIEHYRGIPHRKLLTAL QLRANVYPTREFLARGRQERQIKSCRHCQAEIESCSHIIGYCPAVQDARIKRHNQLCELLIT EAKKKDWIVFQEPLLKDNQNELFKPDLVFVKDNQALVVDVTVRYESKPTSLADAATEKVKKY QHLKDQVQELTNATFIKFMGFPTGARGKWYPGNYELLAELGLSSSRQDKVARRMSNRALFSS VDIVHMFASRSRTILKPLHANDSPLTSQNS 49 (13) R2PufMau RT ECRTVLISKSAAPERRNDINNWRPITIGSTVLRLFSRILTARLTKACPINPRQRGFIKSAGC AENLKLLQLLIRNAKKEHRPLGVVFVDLAKAFDTVSHSHIIAALKQKGVDEHIIALISNLYY NINTYIDLKKEKSDPIGIQIGVKQGDPMSPILFNLSIDPLLCKLEEDGSGFQHCAKKITAMA FADDLVLLSGSWEGMQKNIEILEVFCELTGLKTQGEKCHGFYIQPTKDSYTINDCPPWTING TPLNLIEPGSSEKYLGLQI 50 (13) R2PufMau 5'UTR GGGGTCATAGTTACTAACTGGGCTTAGCTGCAGAGGTCACACCTCCTCGTGGTCCCGCTGGA TACCCTTCTGGGTAACTAAGTTGACCTCTGCCCCAGATTGGGAGGGTTACCTCCCCTATCGA TTGGCTTCACCAACCATTTGATAGTAATTAGCAGGTGATACAAATTTCTGGCACCGAAATTA TTTCGCTGCCCAAAGCCTATCCCCACGGGCTAAAGTTGGGGATATCTCGACAGTTCAGAGGG TGGTTCTGTCGGATTAGTCTAAACCCTCAAAC 51 (13) R2PufMau 3'UTR CCACTCTCACGACGGTCTTACTCGTTCAATCCAAATAACATGACGTGTCACCTTTGCCAAAT TTGACACCAATTACTGGCCATTCACAGGTGGACGGGCCACCTTTACTTAACCCGGAAAAGGA AC AT AT AT AAT T TAT AT GT GT T C GAT AC C 52 (14) R2Hal ORF MGRPMRISFVSVATQTSPLDLRDNAVSRSIRDHKPGGLLEGRFEIRGLEFVNSDLEGLKSQQ SPTLSDLLAVLPEVYEVPNSFSLRDKNTCPTPVEDENEEEESSPLGAVAGTSPVPSTPVSRS RDDLPAESTPVVKIPDKNTSCPCCGNVTGKLSGLIEHLKRAHGKKKILFQCARCGRTDVKHH SIACHFPKCKGPVEASPERSWKCEVCEKTFETKIGLGQHKRLVHPVTRNLERITAARPKTGT NMRGAHRRCWTEDEVELLRKLDKQYEGQKNINKLIAEHIPTKTTKQISDKRRDLHKSPVKKG KDQGQKKHLELEGEHLAEGEHLVCVGSETEGGLKSRYRKTVSEWVTSGKLSILHGMFEQVIE GEEDPAIVADKAMKDCFACLASKSLELKASQGRPRQVAQTARPSEPPKGWMKKRAVKRGQFL RFQRLFYLDRGKLAGIILDDVESLKCGIPQDEIHNVFKSRWESPGTFKGLGAFRSKGLADNS AFEAMITAKEISKNIQEMNKNSAPGPDRLSLRDIIKIDPHFLQLMEVFNLWLVTGIVPDWK ECRTVLISKSSLPERQMDINNWRPITIGSIILRLFSRILTARLAKACPINPRQKGFIRSAGC AENLKLLQLLIKDAKKEHRPLGWFIDLAKAFDTVSHHHLIAVLKQKGVDHHIITLITNMYQ 53 NTRTRITMKNEQSDPIGIQIGVKQGDPMSPLLFNLSVDPLLCKLEEEGSGYHHDSKGVTSMA FADDLVLLSGSWEGMQSNIKILEAFCELTGLRTQGEKCHGFYIQPTKDSYTINDCPPWQING TPLNMIEPGSSEKYLGLRIDPWTGISKPELLVKIRDWLQRIGEAPLKPFQKVDILKGYTIPR LIYLADQADVKATYLEELDLTIRTTVKEWLHLPPSTCDAILYSSTRDGGLGITRLSGLIPS I QARRLHRIAQSSDEVIRSIVKQEGIEKDFEKLWLTAGGDRNKIPSIWDPRAIRVTSEERGED EFASEWEIPTPKTIFPKPCDWRKQEFINWTKLQSQGRGIANFEKDKISNNWLERYRGIPHRK LLTALQLRANVYPTREFLARGRQESHIKSCRHCQAENESSAHIIGYCPAVQDARIKRHNQLC DLLITEVKKKDWIVFQEPILKDEQNEIYKPDLVFVKGDQAMVIDVTIRYESKLSSLADAAAE KVKKYCHLKSQIQELTNAKNIKFKGFPVGARGKWYSGNYEVLKALGISTSRQDKIARCMSRK ALFTSVDIVHIFVSHSRSIVRT (14) R2Hal RT ECRTVLISKSSLPERQMDINNWRPITIGSIILRLFSRILTARLAKACPINPRQKGFIRSAGC AENLKLLQLLIKDAKKEHRPLGVVFIDLAKAFDTVSHHHLIAVLKQKGVDHHIITLITNMYQ NTRTRITMKNEQSDPIGIQIGVKQGDPMSPLLFNLSVDPLLCKLEEEGSGYHHDSKGVTSMA FADDLVLLSGSWEGMQSNIKILEAFCELTGLRTQGEKCHGFYIQPTKDSYTINDCPPWQING TPLNMIEPGSSEKYLGLRI 54 (14) R2Hal 5'UTR ACGGGATCATAGTTACTAACTGGGCAGAGCTGCAGAGGTTACACCTCCTCGTGGTCCCGCTG GAT GC C C T T C GGGGTAACC AAGT T AAC C T C T GC C C C AGT GT GGGAAT T AT AGAT AC T T C CC C CCTATCGTCTGGCCTCACCGACCATTCGATAGACTCAGCTTGGTGATATAAATTCTTGGCAA CGATTTTTTAATCGCTGCCCAAAGCCTTGCCTACGGGCACAGTTGGGCTCAGTCACACAGCA CTTGAGGGGGTGTTGTTTGACTTAGACTACTCCTCTATCTGGACTGGCAAA 55 (14) R2Hal 3'UTR TTATTGCTACTGTTCTGGTTATATTGTTTTTTGCTGTATTACTGTTGGTTGTTTTTATTGCA TTTATTGTTCTGTCTTATATTGTTCTTGCTATATTATCATTCATTGCCTTGCTGTATTACTA TTAATTCTTTAATAAAACTACCCCTGGTACTCCTGCTCTGTTCCCTTGGCACTGGAAAGGTT GGGAGAGTAAGTCGGAACTCGTATTCATGACGTGTCACATCAACCTAAATTTTGACAAAATA GTAATTGGAATTGACAAATTTTGCCAAATTGGACTACTCACTGGATTGGACTCAGGTGGACG GGCCACCTTTACTTAACTCGGAAAAGAAACATATATCCTTTTATGTGTTTGTTAAA 56 (15) R2EmyOrb ORF MEKSNLYFYTGLALDRVNNAPAVGFDAPADSVKYIRGVIRVAGPMDKMVWTIMKSHEHESEN QVLPVEHGEEVEETVCDDHGEEILSILPMVFTRDTFNDLTMESFNPDFKYLSTFDDPYVSES GYLNAHLVNGSSLLNSFRPSTDFNRDRNKDLNSTGSNINILESSSWKDGVFYLEYPVDSFNC PICPQILPTFGKWAKHINVVHKSKAIRWCSKCGKSSQYHNIACHYPKCIPKKADTPMKSHT CSVCGLGFHTRSGLSQHCRHRHPAVRNEQRKEDMAAKSKIKEGSTRSRIWTKDEVAQLIQLE RKYIGKRNINKCIESEMRTKTNKQISDKRRELAKKKLWTGDREEVTEVEDIRVNILEIPPP RERIFPLKGHPEVDLVEKICKRGKQSREGREIINSLGEIEGLLKEDLTKALGWAMLEKLCYS LVEGKDPRNESQIELRNKGKGKMRKEGRRKQFNAIRRYATKKAKYKFYQQLFDKDRRRLTRI IMGEPDKAKCAIPMKEIEEYYVNILGTIGHGNMIGWPSSTENADNDILMSPISVDEIRIALR EIRKDSAPGPDKVKVSNLWDIFNLDSLILTKIFNIWFLNRQVPDEFKKNRTILIPKTQDEEE MKKLTSV7RPLTIGSVWIRIYTKILAKRLVETVKICSRQKGFISAPGCEENIAILDNLIKGAK RNGNEIAIVFVDLAKAFDSVGHGHIIAGLRRFGIDEHFIDIIRBLYDNCTTRVWVGDEVTE S ILIRRGVKQGDPLSPILFNIAMDPLLTRLEVEGSGFYVKGNGVTSLAFADDVAILSSSYKGM IKNLGILEEFCKNTNLSVNVKKTKGFHILTKHKTYWNPKDNWQIGSEEIEYVQPGDFEKYL GARIDPWIGVGGPVLKEKLKDWSENLIKAPLKPAQKILILQTYILPKLFYNLLLIEPPFNLL NDLDVLVRKIVKEILHLPQCTTDGIFYSRGRDGGLALTKFSVQIPNMLIRKWRRHIVSRDDW MDLSYLYAGENLVDKILSFSAVTSHPKKWREEEFLRWSELRCQGIGIKYFKNDLISNSIFRN SSKVKSSAYTAALQLRANIYPTRETLARGRGGVNALCRWCGKVRETVPHISGQCYKTKNART KRHNRWSAWDKVGKLGWKAMIEPHLRNSKGELRKPDIIFIKGDTAWVDVTVRWEDNAGS LEQAHSEKVAYYLELEEEIKNLTGGKNIHFFGFVLGARGKWSEGNNDLLQLLGMDRSKNFKE SICRLVLYSTIGMMAIFSDR 57 (15) R2EmyOrb RT KNRTILIPKTQDEEEMKKLTSWRPLTIGSVWIRIYTKILAKRLVETVKICSRQKGFISAPGC EENIAILDNLIKGAKRNGNEIAIVFVDLAKAFDSVGHGHIIAGLRRFGIDEHFIDIIRDLYD NCTTRVWVGDEVTESILIRRGVKQGDPLSPILFNIAMDPLLTRLEVEGSGFYVKGNGVTSLA FADDVAILSSSYKGMIKNLGILEEFCKNTNLSVNVKKTKGFHILTKHKTYVVNPKDNWQIGS EEIEYVQPGDFEKYLGARI 58 (15) R2EmyOrb 5'UTR TGGCTCTCCATGCGTCTCTGGACCCTCTCAGCTGTCGGGCTTGGACGGAAACATTGCCTGAG GGTAGTGAGAGAATGGGTTATCGGTGAGGTGGGGGTGGGCGTGAGCCCGGTCAATAGGGGCA ACCCCTACCAAGATCTGAGCCTTTTCTCACACGCCCGTTAGAGCTCGACATTATGCTGTTTG GGACCCCTCTTTGAGGAAAGCCTCTGGATTGCAAGTCCAACCGCTACCTCCTCGTGGTGAGA GTCGGTAACTGGCTTGGATAGCCAGGCGGATTGCGGAGGACGAACCCACATCCCACATTCAG TGGGGTGTGGGACGGGGTTGGGCAGCCCCATATGGTGCCACATGGATGCCCCCCTGGTAAGG GTAGCCTCCCCCAGGTACGGGTTGACTCCCCCTGGTAAGGGTTAGATTCCCCCTGGTAAGGG TAGTCTCCCCCAGGCACGGGTTAGTTTCCCCCTGGAAAGGGTAAGTTTCCCCCAGGTACGGG TTAGTTTCCCCCTGGAAAGGGTTAGTTTCCCCCTGAGAAGGGTAAATCTTTTAGCT 59 (15) R2EmyOrb AGATCCCGGAGTTTCCATTCCGTGTATCTTGCCAAAACTAAATTTTAGCTATTTTGGTTTCC AT GC T C TAAAT T T T CAAAT T T T T AAT AT T GT T T T GAAC AT TAAT T T AT T T AGT GT T AT T TAA 60 3'UTR TATCTGTCCTTCAATAGAATGGTTTTAATTATATAATAAATACTTATTAATGGATGAAATTC CAATTTAAATTATTAGTTTTTTTTTTTTTTTTTAATTACTGGATGTGGATGCGGACTGGCCG C GTATAATAAC CAGGAAAGGGCAGGTAGT CACGCC TGTACATAAAT (16) R20piFel ORF MVAQLACADCSRLFPTKIGLSQHRRHVHPTQHNADKLGRVKYSGARWSQQESQSLLRLANNL YPSCGTQTALFARLEQYFPGRSAISIKTRLRVLNWQAQQDESSSGGPDQTIGQITAYSSEAD DYSVWFKQTVDCAVSLLESHADSSLASVDLLAFARGLQSGIMTPEQVLSLLDLHASRTFPHI WKTVSRRRRQLAHRIPVNRKQIRRANYAAIQTLYHQRRKDAASAVLDGSWKDLYKGNCGLPL NAEQYWKQVLSAPKHVDSRPSRVWPSDWSLIEPITGEEVGRTIRLMGNSSPGLDKLTPRML RRFNANALAGYFNLLLLSGGCPPHLCRARITLVPKVPNPTSPDQLRPISVSSILVRCFHKVL ADRWSRRLQLPSLQFAFLHRDGCLEATSLLHALLRHSSATASNLSLAFVDISKAFDSVSHDT IVRSAKAFGAPSPLVRYIAQSYENAVAVFPNSEVHCHRGVRQGDPLSPLLFIMAMDEVLGLS MPQLGYQFHDTLVDGFAFADDWWCAESQARLKEKLEAAAVELGRAGMKINARKTKAMVICG DRKHRATAVSVEPFCFAEELITPLGPTDTVTYLGIPFTFKGKGVFNHRQHLLKLLDEVTRAP LKPHQRMEITRNYLIPRLTYSLVLGQVHRNTLKRLDNYIRQSIRGWLRLPKDTPISYIHAGK QHGGLGTPSLSATIPMQRRARMEKLFSTQCRVLRNWNDSAFGKIVRDLSLPIRVHGACVNT KEELVAAWGDSLHNSVDGRGLRELVASPLSNRWLVFPERVFPRIFIRGIQLRCNLLRTRVRS ARHGHGGQTILCRGNCGQPESLVHILQSCWITHDARCARHNRVARELAKRLRRLGYTVFEEL RAPTSTSFIKPDLIAVRERRATVIDVSIVSDGRGVTVWNEKKQKYGADEYSLAIISALRAIG CDVDFLVHQPMIISYRGICFPQSAKAVIGLGLPKFTVSDLCLLAIVGSLRTYDTFMRGTWR 61 (16) R20piFel RT RARITLVPKVPNPTSPDQLRPISVSSILVRCFHKVLADRWSRRLQLPSLQFAFLHRDGCLEA TSLLHALLRHSSATASNLSLAFVDISKAFDSVSHDTIVRSAKAFGAPSPLVRYIAQSYENAV AVFPNSEVHCHRGVRQGDPLSPLLFIMAMDEVLGLSMPQLGYQFHDTLVDGFAFADDWVVCA ESQARLKEKLEAAAVELGRAGMKINARKTKAMVICGDRKHRATAVSVEPFCFAEELITPLGP TDTVTYLGIPF 62 (16) R20piFel 5'UTR GTCGGCGAGCTGAACCACCTCCTCGTGGTGCCGACTGGGGAGCCTGGACGCCAGTCTGGGTG AGCTAAGAGTTCAGCAACTCCAGACAGGGCTAACCACCCTGTTTGGTTTCAATGTGCTGGTT AC T T T C GAC AAT GT AC ACT AC GAAT CAT CTGGCGCCTCC GC AC C AGT T C C AAC C AGT AC AC A GGAGAGACTCGTGGGGCTCACGTGTGAGGAATGTGGCAAGTGCTGCAAATCGAAAGCTGGCT T GGTAGC C C AC CAT C GAGT T C AC AACAAT GAAAGT GT T GGT AC GAAC 63 (16) R20piFel 3'UTR GTGCACATTCTTGCCATTGAATCTCACACCAGACCCAGTATGACGGACACTTTGTGCCTGAT GTGCGAGTCTTGACTGTGCTAGCGCTTACCGCGCCTTGAAGAGCATTCAGCATTGTTTGTCC TTTCTTCGGCTGTTGATCTTTACACGCGTGTTTCCATACCAAAATTCTTACATACGTTGGGA TTCATCTTATCTGACTGGAACTGTTGGTGGCATGACTTCGAAAGAGACGTTTCTCTCTTTTA TCTCATATTCTCCTGTAACCCTTTCACATTCATCGCTTGCATTTACTTTTTATGTCTGTGAA CAT GC T C T T C AAAAAT AAAC GAT AA 64 (17)R2CapEur ORF MCWSTRVNFLSVGTQTDPKDLQEITTTKTTEDCEEKSEEASEGLGLIYLEFVNSGSMLFSEG GWDEWLGGLPEPYEEPGPPVLGAAVGPPELSGSVPGSHAGPGSGAACRGSAAGHGSIVACRG SAADPGSGGDCRGSAVDQGSGGDCRGSVADLETGGVCSGSAAGPGSRGDCRGSAAGRVSGGD CRGSAAAPGSKRDCRGSVAGRVSGGVCPGSATGPGSRGDCRGSAAGRVSGGDCRGSAAAPGS KRDCRGSAAGRVSGGVCPGSATGPGSGGECRGSAAGRVSGGDCRGSAAAPGLKRDCRGSAAG RVSGGVCPGTATGPGSGGDCRGSAAGRVSGGVCPGTATGPGSGGECRGSAAGRVSGGDCRGS AAAPGLKRDCRGSAAGRVSGGVCPGSAAGRVSGGVCPGSAAGPGSGGECRGSAAGRVSGGDC RGSAAAPGLKRDCRGSAAGRVSGGVCPGSAAGRVSGGVCPGSAAGPGSGGERRGSAAGRVSG GDCRGSAAAPGLKRDCRGSAAGRVSGGVCPGSATVPGSGGECRGSAAGRVSGGGGSGSVAEQ GSGRDCRGSADNQGSGLDYQGSGPNSLEEIKDPSPAGNPAAVNTPIVKIPDSQPSCPCCGNK VSKISGLVEHLKRNHGIKKILFQCARCGKTNEKQHSIACHFPKCKGPEEPPSIKGLICEECQ KIFPTKIGLGQHKRHAHPVTRNNERINASRPKAISARGAHKRCWTDEEVEQLQRLIKQYEGN KNINKLIAEHIPTKTAKQISDKRRLLHNSPTEGETITQDEMGHLEQETEGEQLVPSESHTEG GLKNHYLQLISQWMTDGKLSILQGSFDKIREMNGEATELIPEVIKDSYTRLFKKNTETKASQ GPKRRECKKPSSGPPKQWMKKRAIRRGQFLRFQQLFDLDKSKLASIILDDSESSKCNIPSDQ IHEVFKS RWES PGTFQS LGAFRANGHADNSAFS TLITAKEIDKNIKEMKKNSAPGPDGVSLK DLIKMDPRYTHLVELYNLWLVTGTIPDEMRECRTTLLPKSSKPERLKDINNWRPITIGSTIL RLYSRILTARLTKACPINPRQKGFIRAPGCAENLKLLQLILKTAKKEHRPLGWFVDIAKAF DTVDHQHIITALRQKRVDEHIIALITDLYHKISTRITLKKEQSDPIGIQVGVKQGDPMSPIL FNLSMDPLLCKLEEEGEGFQHCSKKITTMAFADDLVLLSGSWEGMQKNIKIVEVFCELTGLK TQGEKCHGFYIKPTKDSYTINDCPPWTIKGTPLNMIEPGNSEKYLGLHIDPWVGISKPELTE KVKDWLGRIGRAKLKPWQKVDILKGYAIPRLIYLADQADVKTTHLESLDLEIRNTVKEWLHL PPSTCDAILYCSTRDGGLGITRLTGLIPSIQARRLHRIAQSSDEITRTFAREAGIEKDFAKL WVAAGGDKDKIPSIWDPKTVSVLPEELSGEDPLSEWEVAAPRIIYPKPCNWRKQEFTHWTKL ASQGRGISNFEKDTISNKWLEQHRGIPQRKLITALQLRANVFPTREFLARGREGTQIKACRH CQAESETCAHIIGYCPAVQDARIKRHNQICELLMETAKKEEWVVFQEPQLRDTSHELYKPDI IFVKDKKAIWDVTIRYESKPTSLSEAAAEKVRKYSHLKDQIQELTNATDIKFMGFPLGARG KWHEDNYELLEDLGLSGSKREKLARRLSNRALFTSVDIIHMFTSKTRTVIRV 65 (17)R2CapEur RT ECRTTLLPKSSKPERLKDINNWRPITIGSTILRLYSRILTARLTKACPINPRQKGFIRAPGC AENLKLLQLILKTAKKEHRPLGVVFVDIAKAFDTVDHQHIITALRQKRVDEHIIALITDLYH KISTRITLKKEQSDPIGIQVGVKQGDPMSPILFNLSMDPLLCKLEEEGEGFQHCSKKITTMA FADDLVLLSGSWEGMQKNIKIVEVFCELTGLKTQGEKCHGFYIKPTKDSYTINDCPPWTIKG TPLNMIEPGNSEKYLGLHI 66 (17)R2CapEur 5'UTR CAGGAGCTCTCTCCGCTCTCTCCCGCTCGAAATTAAACTAAACTAACGAAATTTCAACGAAA TTAAACGAAAACGCGGCAAATTCGGCTAATTCGGCAAATCCGGGAACAGCAGAACCTCGGCA AAACCAGCAATTTCGACAAAAACGGCATTTTCGGCAAAAACGGCAAAAACGGCAAAATCGGC AAAATCGGCAAATTCGGCAAGAGCAGCTAATCAAGCGAAATTAACGAAATTTCAACGAAAGT AAACGAAAAAGCAGCAAATTCGGCTAATTCGGCAAAACCGGGACGAGCAGAACCTCGGCAGA AACACCAATTTCGACAAAAACGGCGTTTTCGGCAAAAACGGCAAAATCGGCACAAGCGGCAA ATTCGGCAAAACCGGCAAACCAAACGAAATTAAACGAAAAAGCGGCAAATTCGGCTAATTCG GCAAAACCGGGAACAACAGAACCTCGGCAGAAACAGCAATTTCGACAAAAAAAACGGCATTT TAGGCAAATTCGGCAAAGGCGGCAAACCCGGCAAACACGGCAAAAAGAAAAATAAGGTAAAA CGGCTCAATTGGCAATACAGAAAAAGAAAAGACCGCAGCAAAACAGGAAAATTCGCTAAAAG CGGCAAATTCAGGAATTTTTACAAACGCGGTCAGAACTTTGTTGAGGTAAGACATTTTCTAA TTTCTAATCTTACCTCCATGCGGTCCCACGAGACCCACTTCGGGGTAACCGAGATGGCTCTG CCCCAGCCCGGGAACGAACACTAGCTGTTCCCCGCTACCGACTGGCTTCACCAGCCTTTCGG TAGTAAACCTAAGGTGAAACACAGTTTCGGCAACATTTGTTGCCCAAAGCCTTGCCCACAGG CTGCGCTGGGAATTTTTTGCCTTTTTCTTTCACCGGACTTACCTCCATCTCGGACTGACAAA 67 (17) R2CapEur 3'UTR T AAAC C AC AC AC AC AC ACAC CAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA AAAAAGAAAAAC AAAAACAAAC AAACAAAAAAAAAAC C C CAAAAAAC C C C T AC AC T T T C C AC AC AAT AT GC AT GT T AC ACAT AGAT T CC T T C AC T GT TAT T AC C T GT T TAT GACAT AT GT ATT A C C AAT T GT AAAAC T AAC CT GC T C AC GACAT C T AAAGC C AC AAGC C AGT T AGAAGGGT AAGAT CTGGGAAGGACTCCCCACTTGAACACCGATGATAGTATGTGGGGACGAAAAGTGGACTCGAA GGCATGACGTGTCACCTTTACCGATTTGGCTAACCACCACCAAATTTGACATAGGTGGACGG GC CAC C T C TAC T TAAC C CGGAAAGAAAGCATAGAAAATAATTT CTATGTATAT TAA 68 (18) R2DeCI ORF MKVSDILSYRMARGPGYQRAMGGSQEAGSQPIITRPPRKLDMARVMFVSVGTQTNYEDAKPV ASDDTQTWTGNENELIPFSLTIWNSSFQEPRPSESEIETDGADIGWLQTGESVEDLFDDNGE EDEAHLSELEASGYALEHSLLVEPVLGSENTSEGETVTITLPNSMIHCQLCGEVPGGPMKAQ EHFVKFHRDVPWFSCGKCGKGDQNPRSILSHHAKCKSGAPQTSPARGHECTLCGQSFGTIS GLSQHKRHVHPTERNEERIVAASQPSKKKGRKLQLWSQQEIERLRQLEVTYKGARTINKLIA TELGNKSHIQVAEKRRQLRESATPESTQVVGADPLAFLMTAPTMISVPSEIADSLRRETARL YGPAQEDGEDEVTTALRRWAVGNEPIEKTVEKVTAELLSEAVSSCDKKTHYLREKRDKVRTY TSYEWMKRRARSRALFGRYQCQYFKNRARLAALILDGNITSKCQIPASEVHDVYKKKWESST QYGGLGSFTLGGCADNSVFEGLITAEEVGENLAAMNRTSATGPDKMNWKDVKDLCDGSTWD LYNAWWATGKIPVAVKQCRSILLPKTADQEQLMEIGNWRPITIGSMLLRLFSRILTKRLARA CPLNPRQRGFVQSPGCSENLMVLKSIMEQAKRERKHLAWFIDVAKAFDSVSHNHIVDVLRR RGLDSHVIGVIQNSYEDCHTSIEVGGTKTPEIAIRTGVKQGDPMSPLLFNLAIDPLLATLET HGVGFQTEGGKIAALAFADDLVLLSDGWKGMSHNLSILEKFCNLTGLTVQAKKCHGFMITPT HDSYTVNNCQPWSIERAELHMVGPEESEKYLGVRIGPWTGISKPDTESQLQTWIQKIDEAPL KPSQKWILNDYALPRLIYRADHAEETSVRLARLDGLVKRAVKAWLRLPHSTCDGLLYSWRK DGGMGLLKLADSVPSIQVRRIQRVAHSEDPTIRQLMNSSRAQTRFDKAWKRAGGTPDTAPAL TDPITQSVNLETVSDGSILPQKVNYPVPRDWRKDEFEYWCRLPVQGMGTVCFRGDTISNHWL RNHRGFRERHYIAALQLRANVYPTRESLNRGRKGALLHCRKCSSKYESCSHILGQCPAIQAA RIARHNKICDILGDEAKKLGWETHKEPRLYTTMGELRKPDMIFVREGVAIVVDVTVRWEYDS LSLAKAASEKVEYYQNLEQQVRDYTSTHTVHFFGFPVGARGKWHSKNDLVLQLLGVTKGRMK ALGRLVARRALLYSLDMLVMFGGGTYSEHI 69 (18) R2DeCI RT QCRSILLPKTADQEQLMEIGNWRPITIGSMLLRLFSRILTKRLARACPLNPRQRGFVQSPGC SENLMVLKSTMEQAKRERKHLAVVFIDVAKAFDSVSHNHIVDVLRRRGLDSHVIGVTQNSYE DCHTSIEVGGTKTPEIAIRTGVKQGDPMSPLLFNLAIDPLLATLETHGVGFQTEGGKIAALA FADDLVLLSDGWKGMSHNLSILEKFCNLTGLTVQAKKCHGFMITPTHDSYTVNNCQPWSIER AELHMVGPEESEKYLGVRI 70 (18) R2DeCI 5'UTR AGCGTGCTTCTCCTCTGGGCAAGGAGACGGAGTCATAGTGAAGGCCCTACCTCCCCGTGGTT CCCGCTGGAAATGACAGGTAAACACTCCTGTCAGCTAAGAGGGTCTGCACGTGAAAACATCG CCCCCGGGTGGTGATGACCTGACACCACTCCGGTAAAAAAGGTCAACTCAAAC 71 (18) R2DeCI 3'UTR T GAT C GGAT CAGACAT T TC AAC C AGAC AT GGAC CTCCCAGCTGGTAGGCCC TGGGAAAC TAG GCCTCCCCGTGTGATGCCACCCTACACGGTTGACGAAACCCACCGGAATTGACACCCTTTCC CCCACCCCCATCCCCTTTCCCTTTCCCCTACGGGAATCTCGTTCATCCATGATGATTATTTC ACTGGATGAACGAGGGGCTGATGGGCAGCTACTAATAACCCAGAAAGGATGCAACACACCAT CGTTGCAGCATCGAAAC 72 (19) R20nki ORF MSQGWHNGRKRPRHPPPPSPSNGRKMESIHLSSQWDQTGIPKLAPWGAFGHLQVERSGSTT ALPLGSPGSKSYERPTQNKSPKGGRSEGPPTVRAGAPVAPSEAGGGTGERVRVKPPKRKKPS 73 E PPKGAAAAGE S GKAIATD SMC IEIPRTEIECGTCGATAATVKRLVDHMAAKHNEVKLT FKC AKCGKRSVNRHSIACHAPKCKGVQGTPEGKSKKFRCMACQGGFGTASGLSQHMRHRHIAAWN QERIQRERIAEGRLEGKKSWSPDEVRALRELSRTHSNGESPERKIAEGLGTNTSEEQVRWKR RKLALDNVPEGTEGPSWGATIMGLTKPAMQPPEVKGVAAALREQKQVAKEEEEGETAMGRIE REAAEIIQLLGKTDRGKGGTKPAKAKTQPALQRGWVRRRREKRDEYKQHQTLYKQDKRKLAE LILDGTAKRECRIPIEDLTKVYSAQWGDTGPFEGLGQFRSTGKADNTHFNTPITASEVLDNL TAGKKNSAAGPDGISRKELLEWDAKGEKLATMFASWQTVGKIPKAFKQGRTTLLPKSMREEE LRETSGWRPITIGSTVLRLFSRILTGRLERACPINPRQRGFIATPGCAENLMILNGIIYQSK AERSELAWFIDFAKAFDTVSHGHLIHVLRERGLDSHWGLLKDSYEGVYTTVRTREGETQP IEMKKGVKQGDPMSPLLFNLALDPLINKLENVGEGYRFEGKKVTTLAFADDLVEMSD SWAGM QHNVNIVEAFCKLAGLRVQPKKCHGFMVRRGDAAFTINNCREWAIGGENMHLIDPEKTEKYL GLKVNPWLGIAKKDRGAQMAEWIERIHRSALKPSQKISILNIHALTRVMYTIDHGDVGRTQL NALDGLVKTAVKRWLRLPPSTCDGLLYARNRDGGLGITKLASVIPAMQARRLFCLSNSPDQL TRAVTTYMTPQAEYEERWAQAGGDREQTPTLGKRQEDTPADRDDTERTGQEGAGKGEERTYK TPCDWRS IEFKGWAALPVQGDGIGEFQQDHTSNSWLADPEAAGFRERHYMAALQLRANVYPT REALARGRSKEGAACRRCDHKLETASHILGKCPGVKMARLRRHDLICELLVEEAEKLGWAVT KEPRVRTAEGRLRIPDLVFVKGRLGWADVTVRYERNEGTLERGRKEKVDKYLPIAPIIAKQ FKLSRVLVYGFPVGGRGKWPTSNYELLQTLGMGGTRSASFAKLISRRTLLYSLDILKAFGLE CKAGGPTGRKGGREDDDDE (19) R20nki RT QGRTTLLPKSMREEELRETSGWRPITIGSTVLRLFSRILTGRLERACPINPRQRGFIATPGC AENLMILNGTIYQSKAERSELAVVFIDFAKAFDTVSHGHLTHVLRERGLDSHVVGLLKDSYE GVYTTVRTREGETQPIEMKKGVKQGDPMSPLLFNLALDPLINKLENVGEGYRFEGKKVTTLA FADDLVLMSDSWAGMQHNVNIVEAFCKLAGLRVQPKKCHGFMVRRGDAAFTINNCREWAIGG ENMHLIDPEKTEKYLGLKV 74 (19) R20nki 5'UTR AGAGGGGAAAGAGCACCCAGGGGGCCCGACGGTCCTGACGACGCAGGCTAGGTAAGGCGCCC TGG 75 (19) R20nki 3'UTR T GAAGGGGGCAGGAAGGGC CAGC AAAGGC GC GAAC GAGCCAGATC CGTAAC CT AT GGGATAA GGATTGGCACGAAAAATAGGCCGAATGAAGCGTGACCTCGAGCGGACGCCATCGAGAGAAGA GGTCGCAGAGTGAGCTAAGTGAGGCAGGTAGCACCCCCTGCGACCCGAAAAAAGGTGCCGCC AGTGGGTTGGTAGCCACTGGGGGGAACCCCCGATCTACCCCGTCCTCCGGCACCGGATCGGA GCGTCCCGAAGGGCCAGTTAGTAGGGAAGTCCGTTGATTACGCCGAAGAACCGCTCGTTCAA CCTAGGCTGGGTTAAAGCGCTAGACGTGAGGAGTTTTTGGGAATTGTCGCCACGAGTGTGTT GCATCGTGGTTATGTCGCCTGTAAGGCCTCCGGTCGGAAGGTAGGCGGCTGACGCGCAGCCC AAAAACGCGGAATTGTCAGAGCTCGTCGGGCCTGACGCGACCGGATGTCAAAGTGAATGATA TTCAGACAGCGGGGCTCGTGTAATACCCTCGTGCTCCTCATGCATAGCATGTAAAAATCGGG GTG 76 (20) R2AhaPra ORF MPYRPSRGIATGYLTIVYSPSPSGHMDSSDKDGNATGAGTQNRADNPRYPCFCGSTFRSKRG LGLHRAHKHPAVLNAERLAVLPTKRLTWTQEDDEALKRLSDKHWERGMLKKDLITLLTSYFP DRSFEAVKKRLQLTKWAPPEENPERLERPHRAETPERVDAHLADPTETLQSHGPDPTTATSW RRALLVAAADRFKETKLGAEELNQMVRDIQTGELSRKQCRARLRQHAKQWFPHKWKPSKPKP ANASCLKNKKAIRRANYAMVQKLYRLRRRDAASTVLSGRWRNAYRGPAPLPPEMEEYWASVF QTPSANDDRSPAEPAAVLWSLVAAITPSEVTSALNGMKDSAPGLDKIPAEELLTWDQPSLAA YYNLLLAAGGP PKHL SC SRWFLPKTDEPSAPGDYRPISIASTILRAFHKILAWRLRDTLQL SPLQHAFLQRDGCLEASTLLHSIFRRIHTSRVPCAMLFLDVAKAFDTVSHKSLFRVAYEAGL PPPLVSYLQHLYKRSSVKLAETTKCGRGVRQGDPLSPLLFILVIDDIVKRSLPDVGFDFDGQ RVGSLAYADDLVLFAEKSTRLQEKLNLLSEALQQAGMALNAKKSHGLTIARDGKRKCMALVP TTYECKGDTIQPLGTDDQVRYLGLQFNWKGRIVPKHTGKLDSLLNELTKAPLKPHQRIKLLT TFLVPKFTHELVLGHAHRNTLKRLDCLTRAAVRRWLRLPTDTPTGYFHANVLDGGLGLPCFS TSIPLLQQKRLEKIALNPATLFQIVQRQDSFRSLAQRMDRPCRLGGAVATTKAEVREGWQIM LSASVDGKELSIPQVDKASHEWLRRPARVFPRLYIRGIQLRGGLLPTKARSARGNNRQVTDR TCRGACRAPETQNHILQVCELTHDARCARHNRVLRTLEKQLRRTEARTRMEPVIPSGSSFIK PDLIVEAANQMWVLDVS IVAGYRMEETWGIKARKYGREDRVADIRRWADVPEHTPVFQMPVV ISNRGLLYGPSGEGLRAMGLSRRDLTDLCLLAISGSLMCFDLYKRGTKDWKD 77 (20) R2AhaPra RT CSRWFLPKTDEPSAPGDYRPISIASTILRAFHKILAWRLRDTLQLSPLQHAFLQRDGCLEA STLLHSIFRRIHTSRVPCAMLFLDVAKAFDTVSHKSLFRVAYEAGLPPPLVSYLQHLYKRSS VKLAETTKCGRGVRQGDPLSPLLFILVIDDIVKRSLPDVGFDFDGQRVGSLAYADDLVLFAE KSTRLQEKLNLLSEALQQAGMALNAKKSHGLTIARDGKRKCMALVPTTYECKGDTIQPLGTD DQVRYLGLQF 78 (20) R2AhaPra 5'UTR TTl^AGTGATATAGGACT^ATAGTCATAGTTACAGGCTTGGACGCCTCCGCGTGGCGACCGCCG GGGAGGGTACTTGGTACCCAAGCCAAGATCCAAGCCACCCCTCTGC 79 (20) R2AhaPra 3'UTR ACAATCTGTTTTGTGTGTTGCTTGTATCCGTTGACATAACTGTCTTCTAGCGATTGTATCGC CTTAGAAAGCCTGGCGGGCGGGAAGGGGATAGAGAGATGTATTATGCTTTATATGTATTGTA 80 TACTGATGTATTTTTGGTGTCCGAATACTGATGTATCTTACTGTAAATGTATCATGCACTGC TATAACCTGTACTGTTTTGCCTTGCCTTTCTAAAAATAAACAGTTAAA (21) R2AnnSte ORF MPYRPSRGIATGYLTTVYSPSPSGHMDSSDKDGNAIGAGTQNRADNPRYPCFCGSTFRSKRG LGLHRMKHPAVLNAERLAVLPTKRLTWTQEDDEALKRLSDKHWERGMLKKDLITLLTSYFP DRSFEAVKKRLQLTKWAPPEENPERLERPHRAETPERVDAHLADPTETLQSHGPDPTTATSW RRALLVAAADRFKETKLGAEELNQMVRDIQTGELSRKQCRARLRQHAKQWFPHKWKPSKPKP ANASCLKNKKAIRRANYAMVQKLYRLRRRDAASTVLSGRWRNAYRGPAPLPPEMEEYWASVF QTPSANDDRSPAEPAAVLWSLVAAITPSEVTSALNGMKDSAPGLDKIPAEELLTWDQPSLAA YYNLLLAAGGP PKHL SC SRWFLPKTDEPSAPGDYRPISIASTILRAFHKIIAWRLRDTLQL SPLQHAFLQRDGCLEASTLLHSIFRRIHTSRVPCAMLFLDVAKAFDTVSHKSLFRVAYEAGL PPPLVSYLQHLYKRSSVKLAETTKCGRGVRQGDPLSPLLFILVIDDIVKRSLPDVGFDFDGQ RVGSLAYADDLVLFAEKSTRLQEKLNLLSEALQQAGMALNAKKSHGLTIARDGKRKCMALVP TTYECKGDTIQPLGTDDQVRYLGLQFNWKGRIVPKHTGKLDSLLNELTKAPLKPHQRIKLLT TFLVPKFTHELVLGHAHRNTLKRLDCLTRAAVRRWLRLPTDTPTGYFHANVLDGGLGLPCFS TSIPLLQQKRLEKIALNPATLFQIVQRQDSFRSLAQRMDRPCRLGGAVATTKAEVREGWQIM LSASVDGKELSIPQVDKASHEWLRRPARVFPRLYIRGIQLRGGLLPTKARSARGNNRQVTDR TCRGACRAPETQNHILQVCELTHDARCARHNRVLRTLEKQLRRTEARTRMEPVIPSGSSFIK PDLIVEAANQMWVLDVS IVAGYRMEETWGIKARKYGREDRVADIRRWADVPEHTPVFQMPVV ISNRGLLYGPSGEGLRAMGLSRRDLTDLCLLAISGSLMCFDLYKRGTKDWKD 81 (21) R2AnnSte RT CSRWFLPKTDEPSAPGDYRPISIASTILRAFHKILAWRLRDTLQLSPLQHAFLQRDGCLEA STLLHSIFRRIHTSRVPCAMLFLDVAKAFDTVSHKSLFRVAYEAGLPPPLVSYLQHLYKRSS VKLAETTKCGRGVRQGDPLSPLLFILVIDDIVKRSLPDVGFDFDGQRVGSLAYADDLVLFAE KSTRLQEKLNLLSEALQQAGMALNAKKSHGLTIARDGKRKCMALVPTTYECKGDTIQPLGTD DQVRYLGLQF 82 (21) R2AnnSte 5'UTR GTTACTGGGTTGATGACGATAGTATAATCCTCCGCCTCCTCGTGGCCCCGCCGGACAACGAG TCTCTGACTCGGCCAAGTGAGGATTACATCAACCCCTATTTTAACCCTCGGTCGTCATGGTG T GCAACAGT T T GT GC AC AGAAAAC T GC C C GT AT T T T C T C GC GAGGGC GAAG 83 (21) R2AnnSte 3'UTR CTCAAGCTCAATTTGGACGACCCCTAAATTTTAATCCTAATTTTAAAAGCTTTTTAATCTTC CTTTTAAAAATTAAAATTTGTTGTATTTTTACAAAGAAATTTTGTTTCTAATTGGCTTATTT TTAAATTTTAGTTTAGGTAGGTTGACATGTCGGGAGCTTGTGATGATTATACCAAACCCTGG TCAAAGGCTAACACCAACATGGTCTGAGGCCAGGTGTCATGCTGCGTTAATTGGATTGACTG ACCTTAAATCGATGGACGGGCCATCAAGGGGCTGGTCACCCCTTACTAACGCGAAATAAGAG GCTTCCCCCTCAAACTTCAA 84 (22) R2AriEle ORF MDPSNKDGNASSVGTQDTNTRPSYRCFCGSQFNTQRGLGRHQAHRHPAQVNASRVAALPTKR LAWTQEYDEALKRHSDRLWQSGMTKTKLYPLLIPYFPERSLEAIKKHLLLTHWVPPIEASEH NPPQEHPERPENPDRPPTIQQPPTSPVAPPQNGPGCRNATSWRGAILAFAADRLKETKMGGE ELAQIARDIQTGVISRKQCRARLNQHAKSWFPHKWKPSVTRPAGANCQWSKNAIRRANYAEV QKLYKLWRRDAASTVLSGRWXNAYKGPAPVPPEMEEYWAAVLKTPSAIDRVPAEPPAVLWSL ITPIVLSEVTAALNGMKSSAPGLDRLSATELLSWDQPSLAAYYNLLLAAGGPPKHLSCSRW FLPKTEDPKTPGDYRPISIAS TILWAFHKIMAWRLRDTLQL SPLQHAFLQRDGCLEAS TLLH TIFRRIHTDRVPCAROJFWVAKAFDTVSHMSLFRVAYEAGLPPPLVSYLRHLYKKSTVRLAE TTKCGWGVRQGDPLSPLLFIMVIDDIIKSSLPDIGFDFDGQRVGSLAYADDLVLFAERSTRL QEKLDLLSEALQRAGMALNAKKSHGFTIARDGKRKYMALVPTPYECKGDAIQPLGTDDSVRY LGLQFNWKGRIIPKHTGMLDSLLNELSKAPLKPHQQLKLLSVHLVPKFTHELVLSHAHRNTL KRLDCLTRAAVRHWLRLPTDTPVGYFHAHVLDGGLGLPCFSTMIPLLQQKRLEKVASNPATL FQIVQRQTSFQTLESRMDRPCRLGGTVVTTKAEVREGWQIMLSNSVDGSELSISEVDKASHE WLRHPARVYPRLYIRGIQLRGGLLPTKARSTRGNNRQVTDRTCRGACRAPETQNHILQVCEL THDARCACHNRVLRCLEKLLRRKGLCTRLEPVIPSGASFIKPDLIVEVTNQLWILDVSIVAG YRVDETWDIKTTKYGRPDRVADIRRWAAVPATTPVVQHPWISNRGLCYRPSGDGLRALGLS RRDTMDLCLLAIIGSLKCYDLYQRGTKDWNV 85 (22) R2AriEle RT CSRWFLPKTEDPKTPGDYRPISIASTILWAFHKIMAWRLRDTLQLSPLQHAFLQRDGCLEA STLLHTIFRRIHTDRVPCAMLFLDVAKAFDTVSHMSLFRVAYEAGLPPPLVSYLRHLYKKST VRLAETTKCGWGVRQGDPLSPLLFIMVIDDIIKSSLPDIGFDFDGQRVGSLAYADDLVLFAE RSTRLQEKLDLLSEALQRAGMALNAKKSHGFTIARDGKRKYMALVPTPYECKGDAIQPLGTD DSVRYLGLQF 86 (22) R2AriEle 5'UTR GAAGAGCGTAGTTGCAGGCTTGGGCACCTCCTCGTGGTGACCGCTGGATATAGTACTTCATG TACTAGAACTAAGATCCAAGCCACCCCTCTACACGACTATTGCTTTAGTAGAGGGTTAGTTA CTGGTTTACTTATTTATATATCGTACTAGTCCAAGTCCCTCTGGAACT 87 (22) R2AriEle 3'UTR TATGTCTTGTTATGCTTATGCTTGTATGTTGTTACCTGTCTATTAGCGAGCAATCGCACTTG GAGGGCCTGTCGGGCGGGAAAGGTCTAGTCGGTTGTATTTGCTATATTAACTTGTATACCAT GTATATTGATATCATGCATATGTGATGTATCTTGTTGTATCGTACTATGCACTGCTTTACCA TGTACTGTCTTGCCTTGCTTAATCCAAAAATAAACTGTCAA 88 (23) R2AspMar ORF MFPSKRSLAMHRHHVHPDEVNRERAMRVPTKRLAWSEEDDSALVRHATLLWAPNMLRKHHLE LLVPFFPGRSAEALKKRLQILKWLPPSHPTLIDPPTPTTRVEDPATSTSSRTEDIPLLSTRI PSTPATFISQDPLLPPVTPTPTVTPQVTSTSTPSWKEVLLDFAANNLHDPRLGADDLLAIVS KIQSGSISSAEAARLLEDHAERWFPHTWAPSKRKHRPLGPTPTSRQLRRANYAAVQKLFHLR KKDAASCVLSGQWRQAHSGPKPTVPGMDDYWAQIFEHPSAPDRREPTPQDDVAWSLLDAITA AEVT SAL RDMGNS AAGL DRLSPSTLS TWD P S SIAAYFNLILAT E S VPKQIAKARVIFLPKTE EPSSPSDFRPISISSVLLRAFHKILARRMTSTLRFSQLQHAFLKRDGCLEAGSLLHAILRKI HDDRVRASLIFLDISKAFD SVSFHTLLRVAKS SGLPPPLTNYLVSLYDHPTVQLE SRTVTCG RGVRQGDPLSPLLFIMAFEDILQSSLPEVGFKLDGHKIPALAYADDLVLFARKPERLQEKLD GLWSLAAAGMSVNAKKSSGLTITKIGKTKTMVLLPHIYTAGSTAIKPMGPSDTIRYLGVDF NWKGRVAPKHTSKLDQMLKDLSMAPLKPYQRLDLLKNFAIPRLTHELVLGNAHRNTLKKMDV LVRSAVRRWLRLPKDTPLGYMYAHIRDGGVGLPCLNTSIPLIQKKRFAKLLSNPSPIQRTVV NQKSFKVIQRATDLPVLIGGQAIQSKKEARTAWRDDLRRSYDGRDLFGDPVDPTSHHWVSHP QRVFPRLHLRGIQLRGGLLPTRARNARGRDPTGTPTTCRGACGQVETLNHILQICDKTHDAR CARHNRIVQRLCQFLRKKGIKFWTEPLVPTDTSYIKPDIIVLTNSELLVMDVSIVSGPRMSY SWTLKAEKYGTAKCSSALQHWHGSPIPIRHSPIILSNRGLLYAQSGQALKSIGLTTRDLSDL CLLTIMGSLRCFDHYTRSTMDSSDRGCT 89 (23) R2AspMar RT KARVIFLPKTEEPSSPSDFRPISISSVLLRAFHKILARRMTSTLRFSQLQHAFLKRDGCLEA GSLLHAILRKIHDDRVRASLIFLDISKAFDSVSFHTLLRVAKSSGLPPPLTNYLVSLYDHPT VQLESRTVTCGRGVRQGDPLSPLLFIMAFEDILQSSLPEVGFKLDGHKIPALAYADDLVLFA RKPERLQEKLDGLWSLAAAGMSVNAKKSSGLTTTKTGKTKTMVLLPHTYTAGSTATKPMGP SDTIRYLGVDF 90 (23) R2AspMar 5'UTR GGGTCGTAGTTACATGGCCTGGGCGCCTCCTCGTGGCGACCGCTGGAGATGATGGGGTACGC GAAAGGGGGCAAGTCCCTCGATCCGTCCCCGTCTGAGCTAAGACCCAGGCCACCCCTCTTCT GGGCCAACCACCCAGTTGAGGGTTTCTCTGCTGGTTACAGAAAGGAAAATTGTGAATGCCCC TGGTCCCTCCGGACATCAGGGTAACAGCAGAGACGTCGACCCTGAAGGTGCTCCCAGCCTTC CCTCGTGTCCGCCCGGCGATGTCACCTGCCACTGCGGCCGA 91 (23) R2AspMar 3'UTR GAGGATGGAAGCAGCTCATGACCCGCCACAAGCGGCGATCCCCCTTCATAGTCGTCGTCGAT AGCGGTTATCCGCCTCAAAGTTTACTGTATGCTGTATTTCTTTGTTATTTACTGCTGTACGG T C TAC T T T GATAATAAAATGATAA 92 (24) R2AzeSeq ORF MLTYTEDPKPPGFTDHSSTGRCAGVESLERTPEYSRHLCTCGSEFQSKQGLVMHQFHRHPAE VNAKRLASLPVKKLVWTQEEETALLRHASQAWKKGMMKVELCACLLPQFPGRSGEATKKRLQ RLKWVPPGENIEREVPERDSLPQLTPAIKGHVAPATLPPHKDLWGDQGQNNNIKAPWRRAL LTNMADHLSETKLGVEKLHQIVDGLNSNQMSTDKCRHLMNEHAQQQFPHKWKPSSAWPETKA GLYSKREIRRANYAIVQKLYKLRKRDVAHTVLSGGWKNAYRGHAPLPKNMEEYWSAIFETPS ETDVTTPEVPTEIHWSVMEKITPSEVTNSLKGMRNSAPGLDRISAEELLTWHQPSLAAYYNL MLATGGPPEHLACSRVAFIPKIESPQTPGDYRPISIASTILRALHKILAWRLRDTLRLSPFQ HGFLQRDGCLEATALLHAILRKVHQNRKPCAMLFLDVAKAFDTVSHHTLFRVASAMGLPPPL VDYLEHLYNRS TVKIANKATKCGRGVRQGDPLSPLLFIMVMEDIVRKALPEIGFNLDEQRVD SLAYADDLVLLAEKSTRLQEKLHLLTEALGKAGMTLNANKSHGLTUSrKISKRKQMVLTPTAY DCKGMMIKPMGTDDSVRYLGLHFNWKGKIVPKHTCKLDSMLKEMTKAPLKPYQRLQLLKYHL VPKFTHELVLGHAHRNTLKKLDCLTRAAVRHWLRLPKDTPLGYLHANVKDGGLGIPCFSTSI PLLQQRRFEKIAANPATIFQVIQRQDSFRTQGRRLDLPCRLNGTVVNSRAEVRKEWGNVLAD SIDGRELRYPKVDKASHGWLQHPDRVFPRLHMRGIQLRGGLLPTKARSARGKDRQVAEKTCR GACHCTETLNHILQVCEITHDARCARHNRVLHRLEQLLRKKGLRTTLEPVIPSGPSFIKPDL IVETGTQTLVIDVSVVASYRMKESWDIKVEKYGSSERVNDIRKWAAIPHQVRLHQLPVIVSN RGLCYQPSGEGLRALGVTCRDITDLCLLSINGSLRCYDLYMRGTQGAKVHRLPKNTEGPRRV PPGLHWQ 93 (24) R2AzeSeq RT CSRVAFIPKIESPQTPGDYRPISIASTILRALHKILAWRLRDTLRLSPFQHGFLQRDGCLEA TALLHAILRKVHQNRKPCAMLFLDVAKAFDTVSHHTLFRVASAMGLPPPLVDYLEHLYNRST VKIANKATKCGRGVRQGDPLSPLLFIMVMEDIVRKALPEIGFNLDEQRVDSLAYADDLVLLA EKSTRLQEKLHLLTEALGKAGMTLNANKSHGLTLNKISKRKQMVLTPTAYDCKGMMIKPMGT DDSVRYLGLHF 94 (24) R2AzeSeq 5'UTR CCTATGACGCATTGATTGTTGCAAGGCGAATCGTTGTAGAGTTAAGAGTGGAAAACAGTTAT AAGGGTTGGGCACCTCCGTGTGGTGACCGCTGGATAGGGCTATTACTAGCCTGAACTAAGAT CCAACCCAAAACCCCTGTTTTGCACCAGAACAGTGGGTAGGCTGCTGAT 95 (24) R2AzeSeq 3'UTR CCCCTCCAGGCTCTATCCTGT7\ATAGCGATAGGATTATCGCCTTAG7\AGGCTTAAGGGG7^AG GAC GAGT AGGC C AAT T C GT GT C C GAAC C AC T C C AT AC C T C T C C T C T AT T C GCC T AT C TAAT A ATTTATGTTT^ACA 96 (25) R2AzeSeq2 ORF MLTYTEDPKPPGFTDHSSTGRCAGVESLERTPEYSRHLCTCGSEFQSKQGLVMHQFHRHPAE VNAKRLASLPVKKLVWTQEEETALLRHASQAWKKGMMKVELCACLLPQFPGRSGEAIKKRLQ RLKWVPPGENIEREVPERDSLPQLTPAIKGHVAPATLPPHKDLWGDQGQNNNIKAPWRRAL LTNMADHLSETKLGVEKLHQIVDGLNSNQMSTDKCRHLMNEHAQQQFPHKWKPSSAWPETKA 97 GLYSKREIRRANYAIVQKLYKLRKRDVAHTVLSGGWKNAYRGHAPLPKNMEEYWSAIFETPS ETDVTTPEVPTEIHWSVMEKITPSEVTNSLKGMRNSAPGLDRISAEELLTWHQPSLAAYYNL MLATGGPPEHLACSRVAFIPKIESPQTPGDYRPISIASTILRALHKILAWRLRDTLRLSPFQ HGFLQRDGCLEATA1LHAILRKVHQNRKPCAMLFLDVAKAFDTVSHHTLFRVASAMGLPPPL VDYLEHLYSRSTVKIANKATKCGRGVRQGDPLSPLLFIMVMEDIVRKA1PEIGFNLDEQRVD SLAYADDLVLLAEKSTRLQEKLHLLTEALGKAGMTENANKSHGLTENKISKRKQIVLTPTAY DCKGMMIKPMGTDDSVRYLGLHFNWKGKIVPKHTCKLDSMLKEMTKAPLKPYQRLQLLKYHL VPKFTHELVLGHAHRNTLKKLDCLTRAAVRHWLRLPKDTPLGYLHANVKDGGLGIPCFSTSI PLLQQRRFEKIAANPATIFQVIQRQDSFRTQGRRLDLPCRLNGTVVNSRAEVRKEWGNVLAD SIDGRELRYPKVDKASHGWLQHPDRVFPRLHMRGIQLRGGLLPTKARSARGKDRQVAEKTCR GACHCTETLNHILQVCEITHDARCARHNRVLHRLEQLLRKKGLRTTLEPVIPSGPSFIKPDL IVETGTQTLVIDVSVVASYRMKESWDIKVEKYGSS ERVNDIRKWAAIPHQVRLHQLPVIVSN RGLCYQPSGEGLRALGVTCRDITDLCLLSINGSLRCYDLYMRGTQGAKVHRLPKNTEGPRRV PPGLHWQ (25) R2AzeSeq2 RT CSRVAFIPKIESPQTPGDYRPISIASTILRALHKILAWRLRDTLRLSPFQHGFLQRDGCLEA TALLHAILRKVHQNRKPCAMLFLDVAKAFDTVSHHTLFRVASAMGLPPPLVDYLEHLYSRST VKIANKATKCGRGVRQGDPLSPLLFIMVMEDIVRKALPEIGFNLDEQRVDSLAYADDLVLLA EKSTRLQEKLHLLTEALGKAGMTLNANKSHGLTLNKISKRKQIVLTPTAYDCKGMMIKPMGT DDSVRYLGLHF 98 (25) R2AzeSeq2 5'UTR CCTATGACGCATTGATTGTTGCAAGGCGAATCGTTGTAGAGTTAAGAGTGGAAAACAGTTAT AAGGGTTGGGCACCTCCGTGTGGTGACCGCTGGATAGGGCTATTACTAGCCTGAACTAAGAT CCAACCCAAAACCCCTGTTTTGCACCAGAACAGTGGGTAGGCTGCTGAT 99 (25)R2AzeSeq2 3'UTR CCCCTCCAGGCTCTATCCTGTAATAGCGATAGGATTATCGCCTTAGAAGGCTTAAGGGGAAG GACGAGTAGGCCAATTCGTGTCCGAACCACTCCATACCTCTCCTCTATTCGCCTATCTAATA ATTTATGTTAACA 100 (26) R2AzeSeq3 ORF MLTRSKDPRPPGSPDLSSTGSCDGVASLESSPEESRHPCPCGSEFRTKQGLAMHRYHRHPAE VNAERLVSLPTKKLVWTQEEEAALLRHASQAWKKGMMKVELFTCLLPHFQGRSEEAIKKRLN RLQWVPPVDNPERDVPERNSLPLPIPAVSGHVAPATHPLPEAKMVEDQGRNTGSVESWRRDL LATVADHLSETKLGIEALSQILGGLKSGQISTDKCRALMNDHARQQFPHTWKPSSARPGAEA RKWSQREMRRANYATVQKLYKLRRRDAAHTVLSGRWRTAYRGHAPLPSNMEEYWSAIFETPS ETDAAIPEVPTEIFWSVMGRIAPSEVTSALKGMRNSAPGLDRISAEELLTWHQPSLAAYYNL MLAAGGPPEHLACSRVAFIPKNDNPQTPGDYRPIS IASTILRALHKILAWRLRDTLQLSPFQ HGFLQRDGCLEATALLHTILRKVHHNRKPCAMLFLDVAKAFDTVSHQTLFRVAAAMGLPPPL VDYLKNLYSRSTVRIADKATRCGRGVRQGDPLSPLLFIMVMEDIVRRVLPEVGFNIiDGQRVD SLAYADDLVLLAEKSSRLQEKLHLLTEALQKAGMAIiNASKSHGLTWKVSKRKQMVLTPTTY ECKGGTIKPMGTDDSVRYLGLHFNWKGKIVPKHTGKLDSLLKELTKAPLKPHQRLQLLKGHL VPKFIHELVLGHAHRNTLKKLDCLTRAAVRHWLRLPQDTPIGYLHAHVKDGGLGIPCFSTSI PLLQQKRFEKIATNPATIFQITQRQDSFRTQGRRLDRPCRLNGAVMTSKAEVREEWGNVLSN SVDGKELRCSEVDKASHGWLQHPGRVFPRLHMRGIQLRGGLLSTKARSARGKDRQVTDKTCR GSCHCPETLNHILQVCEITHDARCARHNRVLHRLEQMLRKKGLRTTLEPVIPSGSSYIKPDL IIETGTRRYWDVSVVAGYRMKESWDIKVEKYGRPDRVNNIRKWAAIPEQDLVIQLPVIVSN RGLCYRPSGEGLRALGLTCRDISDLCLMSINGSLRCYDLYMRGTRSDKVRGRPRNTEGG 101 (26) R2AzeSeq3 RT CSRVAFIPKNDNPQTPGDYRPISIASTILRALHKILAWRLRDTLQLSPFQHGFLQRDGCLEA TALLHTILRKVHHNRKPCAMLFLDVAKAFDTVSHQTLFRVAAAMGLPPPLVDYLKNLYSRST VRIADKATRCGRGVRQGDPLSPLLFIMVMEDIVRRVLPEVGFNLDGQRVDSLAYADDLVLLA EKSSRLQEKLHLLTEALQKAGMALNASKSHGLTLDKVSKRKQMVLTPTTYECKGGTIKPMGT DDSVRYLGLHF 102 (26)R2AzeSeq3 5'UTR TCGCCCCACAACTTGACCTTGGTTTTGATGTTGAATGTGAATTGTTGCAAAGCGAATTGTTG TGGACGCGAGATTGACGAACAGTTGCACGGGTTGGACACCTCCCAGTGGTGAACGCCGGATA GGGCCTTGTGCCTGAGCTAAGAGCCAACCCAAACCCCTGTTACGTACCAGTACAGTGGGCAA GCTGCTGAAT 103 (26)R2AzeSeq3 3'UTR GGGACTCCCACAGGACTGCATAGGCAGTGTCCCCTCCACGCACTATCCTGAAGTAGCGATGA GTATCGCCTTAGAAGGCCTGATGGGGGAGGCTGAGTGGACACAATGTGTCACAAACGCTCTT TACCTCTCCTCGTCTTGCCTGTCTAATAATATATGTTAACA 104 (27) R2ChaBot2 ORF MAS GGANEFRCDCGTLWPSARSLAMHNFHRHTEKVMAERREKQPAKRLRWSAEEEAALHRQA DRLWSEGMLSKDLCLLLTDFFPGRSAEAIKKRLQSTRWIPPGQRPPVSPEGNEESSLAEQFD FAMWSKDLLEEAVGNLQEPRMGAELLSRIARGLLTGEFSKEEGVKRLEDHACQWFPYRWKSS VPRKSGNPQMHSNKKIRRMNYAAIQRMYHRRLKDAATCVLSGQWRTAYQPRPEVEGLNEYWT KIFETRSVEDTGCLRTPTRTLYSLIGRIIPSEVTAALKTMRSSAPGLDRITASELLAWHQPS IASYYNLLLVLEVCPRYLSCSRVAFLPKVPVPSAPDDLRPISITSVLLRAFHKILARRLNDE LHLTSLQFAFLQRDGCLDATTLLHSILRNIHHTRSPGAMLFWISKAFDTVSHSTIARIITS AGFPIPLIHYICNLYSNSTVQLGEKMIKCGRGVRQGDPLSPLLFILVIEE ILLAS LPDVGYN FGGQRLGAIAYADDLVLLAEHPQRLQEKFKIFSEALHTTGMVLNPKKSIGLTISRDGKRKAI 105 VWQPHCYNYLGTPIRPLKIDESVKYLGLQFNWKGRINPRHVGKLDEMLGEISAAPLKPYQRI RILTSFLIPKLTHSLVLGLAYRKTLKRADRLVYAAVRSWLRLPKDTALGYFHASVADGGLGI PCLSTTIPLLQRDQFAKLISQTDPLSVIIREQEAFKVVGNIINRPCRINSRWTSKEEARAE WKTSLSQSVDGSELTIPDVDLASHGWLKYPVRVFPRLFLRGIQLRGGVLPTKARSARGNNRV VVDRSCKGLCGTSETLNHVLQSCEITHNARCSRHNKIVQQLEYLLNKIGIKIWVEPIIPSGS SFIKPDLWMKDNQLWVLDVSIVSGMRLRESWNIKIVKYGSTERVNDIVCWFGSPIAVKQLP IIISNRGLCSTFSGSGLRALGLSRRDITDLCLLTVKGSLMCYDLYNRSTRSSGR (27) R2ChaBot2 RT CSRVAFLPKVPVPSAPDDLRPISITSVLLRAFHKILARRLNDELHLTSLQFAFLQRDGCLDA TTLLHSILRNTHHTRSPGAMLFLDISKAFDTVSHSTTARTITSAGFPTPLIHYTCNLYSNST VQLGEKMIKCGRGVRQGDPLSPLLFILVIEEILLASLPDVGYNFGGQRLGAIAYADDLVLLA EHPQRLQEKFKIFSEALHTTGMVLNPKKSIGLTISRDGKRKAIVWQPHCYNYLGTPIRPLKI DESVKYLGLQF 106 (27) R2ChaBot2 5'UTR CTTTCTTGTCATAGTTACAGGCCTGGACACCTCCGCGTGGTGCCCGCTGGATAGGGTATGGG ATCTTATATCCCATGCCTGAACTAAGTTCCAGGCCACCCTCCTCTCGGGAAGACTTAATTAC CCGTTAGGAGGTTGCTGCTGTTTTTTTGTTAAATTGATTAATTTATGTCCGGAGCCCTCTGG T T GAC C GGT GAT AC AGC AGGT AAGT GAGGT AAGAC AGT T GT C AAGAAT C C ACA 107 (27) R2ChaBot2 3'UTR TTTTCGATCTGGATTCGATGAACGACGATTGTCTCCTGTTATGATTTGAATTATTTTCTTGG AGATGTTGTATTTATAAATTTGCTAAATTATAATTGTATCTTTTTGAACATACTCCAATAAT AAATGTAAA 108 (28) R2CroAda ORF MLTDTWLRPPGLPDPSCPGSCPRVASPKSDAECPKHSCPCGSEFGTKRGLAMHRFHCHPAE VNAERLATLPTKKLWTQEEMDGLLRHANGAWKEGMLKTQIFTSLMPHFPGRSAEAIKKRLQ S L KWV PARD NP E RNS Q P LHAT S GNVAPAT L P T P D P S RVD D Q GANIED PAASWRRALLAAAAD HLKEPKLGAGTLKQITQDLLNGKISSGECRVLMGEHAQHWFPHTWKPSSARPEPKARQWKAR EIRRANYAAVQKLYKLRRRDAAQAVFSGSWRNAYRGRAPQPDKMDQYWAEVFETASATDVTP PGSPSEIYWSVVSKITPSEVADALKGMRNSAPGLDRITAEELLTWDHPSLAAYYNLMLAAGG PPEHLACSRVTFIPKVENPQTPGDYRPISVASTVLRAFHKILAWRLRDTLHLSPFQHGFLQR DGCLEATALLHTILRKVHNSRKSCAMLFLDVAKAFDTVSHQTLFRVAVELGLPPPLVNYLRC LYSRSTVRLADKATKCGRGVRQGDPLSPLLFIMVMDDIVRKTLPEVGFDWGQRVDSLAYAD DLVLLAEKSPRLQDKLHLLSEALRKAGMSIiNARKSRGLTITKVSKRKQMVTTPTTYECEGEP IKPMGTDDSVRYLGLHFNWKGRIVPKHTGKLDSLLKELTKAPLKPYQRLQLLKFHAVPKFTH ELVLGHAHRNTVKKLDCLTRAAVRKWLRLPQDTPLGYLHANVKDGGLGIPCFSTSIPLLQKK RFEKIATNPATIFQTMQRQDSFRTQGRRLDKPCRLNSTVVTSKTEVREEWGNMLSNSIDGRE LRHPEVDKASHEWLLRPDRVFPRLHMRGIQLRGGLLPTKARSGRGNNRQVTSKTCRGACQNV ETLNHILQVCDVTHDARCARHNRVLHRLERLLHKKGLRTTLEPVIPAGSSFIKPDLIIETDT HTYVLDVSVVAGYRMTESWDIKVEKYGRPDRVEAIRKWAAIPATKRVEHLPVIVSNRGLCYQ PSGDGLRALGLTSRDISDLCLLAISGSLRCYDLYMRGTRAV 109 (28) R2CroAda RT CSRVTFIPKVENPQTPGDYRPISVASTVLRAFHKILAWRLRDTLHLSPFQHGFLQRDGCLEA TALLHTILRKVHNSRKSCAMLFLDVAKAFDTVSHQTLFRVAVELGLPPPLVNYLRCLYSRST VRLADKATKCGRGVRQGDPLSPLLFIMVMDDIVRKTLPEVGFDLDGQRVDSLAYADDLVLLA EKSPRLQDKLHLLSEALRKAGMSLNARKSRGLTITKVSKRKQMVTTPTTYECEGEPIKPMGT DDSVRYLGLHF 110 (28) R2CroAda 5'UTR TCGACCATTTGGTGTTGATATTGATACTGGCGACTGGCTAGTTGGTGTTGGTTGAAAGCGCT GGCGAGGTTGAGCTGATAATTGGTTGCACGGGTTGGGCACCTCCTAGTGGTGACCGCTGGAT AGGGCTTCGGCCTGAGCCAAGATCCAACCCACCCTCCGTTGCTGGCAGACCCCAGTAACTGA GAT TAAACAGCTGGT 111 (28) R2CroAda 3'UTR GACTACCGAGCGCCACCGGAGGGGACCCAGAGGACCGTCTCGGTGATTAGGCGGTGACCGCC CTGGCCTCTACCTGAAATAGCGATCAAATCGCCTTAGAGGGCTTGATTTGGGGGGTTGGGCA GACACTCTGTGTCATTACTGCCCTTTACCTTTCCACTTCTTGCCTGTCTAATAATAAATGTT AACA 112 (29) R2CucCan ORF MGRQTRMHFMSVATQTYYGDWRKVKVNVIESDHNPPIDVEWEISGLEFVNSGLKEEGYQPFI GVSDLAAFPDVYEALKTPDLVGNVNSPVLTVVEEREEEREDERQSSHGEVAELNPAPSTSMS GSCTELSADGIPVVKVPDKQPTCPSCGALFVKVSGLIEHLKRAHGKDKIWFECVKCGRQNVK YHSIVCHYPKCPGRIEVVESDDFVCGECKRSFSSKIGLSQHKRLAHPALRNEERIENSLPKE STRRGVHRSCWTDEEVELLLKWERQFEGEKNINKLIAEKIPSKSAKQISDKRRCLSKQKEKL KGKDLEEVSHDIEGEHPAKSEGGLNLGLRDIYKRILTEWVSAGKITTFNQTYSDLLEGREHH MSSITEATMTYLASLGKVSGELEASMREGTRKATKQLSSRKHSKGWMKRRAAKKGKFYRFQR LFYRDRVKLAEIILDGRES LKCEIPLDEVHDVFKS RWESQGTHRGLGVFKS QGMADNSVFLT MITEREISKNIKEMKKNAAPGPDGLRRRDIESCDPQFKDLMEIYNLWLVSGKVPDWKECRT ILIPKSTNAERLNDINNWRPITIGSTILRLFTKILTARLTKACPLNPRQRGFIRSAGCAENL KLLQLIIKNAKREHHALGWFIDLEKAFDSVSHEHLIEALENRGVEEHIITLIKDLYRNVTT SVEIKSGKSESIKINIGVKQGDPMSPLLFNLSIDPLLCRLEEKGHGFKHGSRCITSLAFADD LVLLSESWEGMVENIKILEAFCSLTGLKTQGIKCQGFYISPTKDSYTINNCPVWEINGTPLR MIDPEKSGKYLGLEINPWVGISKPELEKDLSEWLDRIGKASLKPLQKVDILKGYAIPRMIYK 113 ADQAEVKASCLEALDLMIRSNVKEWLHLPPCTCDAILYSRSRDGGLGINRLSAIIPSIQARR LHRLAQSSDEAIREFVKKVSIEKEYEKLWITAGGDKNKIPSIWDPRSVMQISEITSGENPGS EWEVSAPKTIFPRPSDWRKREFNNWTNLGSQGIGIRNFVNDKISNDWIINYKGIPHRKLLTA LQLRANVYPNREFLSRGRREAHNKTCRHCPGSTESCAHIIGYCPRVQEARIKRHNIVCKILA DEAKKKEWKIYMEPLIRNDNNELFKPDLIIVKDGAAMVIDVTIRYESTLSTLKEAATEKVKK YEHLKDQIKDLTGASIVRFFGFPLGARGKWYDGNSDVLSDIGLSQSRINKTAIRLSNLALFS SVDIVHIFTSSAATGVT (29) R2CucCan RT ECRTILIPKSTNAERLNDINNWRPITIGSTILRLFTKILTARLTKACPLNPRQRGFIRSAGC AENLKLLQLIIKNAKREHHALGVVFIDLEKAFDSVSHEHLIEALENRGVEEHIITLIKDLYR NVTTSVEIKSGKSESIKINIGVKQGDPMSPLLFNLSIDPLLCRLEEKGHGFKHGSRCITSLA FADDLVLLSESWEGMVENIKILEAFCSLTGLKTQGIKCQGFYISPTKDSYTINNCPVWEING TPLRMIDPEKSGKYLGLEI 114 (29)R2CucCan 5'UTR ACGGGACAATAGTTACTACCTGGGCTCAGCTGCAGAGGTCACACCTCCTCGTGGTCCCGCTG GATGCCTGTAAAGGTAACCAAGTTGGCCTCTGCCCCAGGGAAAAGTTTTGGAGTTAAAGGTT GCTCCGCCC TAT C GAGT AAAC T C AC C AC T T AC T C GGT AGT AGT T AC AAGAGGT GAAAC AAAA ATATTTGTGGCTTGAATTCGTTTAAGCTATATCCCTTGCCCACGGGAAGACATAGTTGGGCG GGCAGCTGACCACCGAGAGGGGGTGGTTACGTTGAAAGTCATCCCTCAAA 115 (29)R2CucCan 3'UTR ATTGTTCTGGCTTTAAAGTTGAATTGTTCTGGTTCTAAAGTACAGTTGTTAATTTTATAGTT GTTAATTTTATGTATTTTAACAGTTATTTATTTATTATGTTTTCCAGATTTTAATAAACAAT ATTGACAGTCTGGTATACAGTACGGGATCTCGTAGTGATTACAGAATCATGACGCTGTCACT TTGGACATGACGATAGGTGGACGGGCCACCCTCACTTAACCCGGAAAAGGGACGCATCACCA TATGCGTTC GACAC 116 (30) R2HalLeu ORF MGRPMRISFVSVATQTSPLDLRDNAVSRSIRDHKPGGLLEGRFEIRGLEFVNSDLEGLKSQQ SPTLSDLLAVLPEVYEVPNSFSLRDKNTCPTPVEDENEEEESSPLGAVAGTSPVPSTPVSRS RDDLPAESTPVVKIPDKNTSCPCCGNVTGKLSGLVEHLKRAHGKKKILFQCARCGRTDVKHH SIACHFPKCKGPVEASPERSWRCEVCEKTFETKIGLGQHKRLVHPVTRNLERITVARPKTGT NMRGAHRRCWTEDEVELLRKLDKQYEGQKNINKLIAEHIPTKTTKQISDKRRDLHKSPVKKG KDQGRKKHLELEGEHLAEGEHLVCVGSEMEGGLRSHYRKTISEWVTSGKLSILHGMFQRVIE GEEDLTTVADKAMEDCFACLAFKSSELKAGQGRPRQVAQTARPSEPPKGWMKKRAVKRGQFL RFQRLFYLDRGKLAGIILDDVESLKCGIPQDEIHNVFKSRWESPGTFKGLGAFRSKGLADNS AFEAMITAKEISKNIQEMNKNSAPGPDRLSLRDIIKIDPHFLQLMEVFNLWLVTGIVPDWK ECRTVLISKSSLPERQMDINNWRPITIGSIILRLFSRILTARLAKACPINPQQKGFIRSVGC AENLKLLQLLIKNAKKEHRPLGWFIDLAKAFDTVSHYHLIAVLKRKGVNHQIITLITNMYQ NTRTRIAMKNEQSDPIGIQIGVKQGDPMSPLLFNLSVDPLLCKLEEEGRRYHHGSKCVTSMA FADDLVLLSGSWEGMQSNIKILEAFCNLTGLRTQGEKCHGFYIQPTKDSYTINDCPPWQING APLNMIEPGSSEKYLGLRIDPWTGISKPKLLMKVRDWLQRIGEAPLKPFQKVDILKGYTIPR LIYLADQADVKATYLEELVLTIRTTVKEWLHLPPSTCDAILYSSTQDGGLGITRLSCLIPSI QARRLHRIAQSSDNVIRSVVKEEGMEKEFEKLWLTAGGDKNKIPSIWDPSAIRVTSEALGDD EFVSEWEVPAPKTIFPKPCDWRKQEFINWTKLQSQGRGIANFEKDKISNNWLKRYRGIPHRK LLTALQLSANVYPTREFLARGRQESQIKSCQHCQAENESSAHIIGYCPAVQDARIKRHNQPC DLLITEVKKKDCIVFQEPILKDERNEIYKPDLVFVKGDQAMVIDVTIRYESKLSSLVDAVAE KVKKYGYLKSQIQELTNAKNIKFKGFPVGARGKWYSGNYKVLKTLGLSNSRQEKVACYLLNK ALFTSVDIMYIFMSQSRTIVRT 117 (30) R2HalLeu RT ECRTVLISKSSLPERQMDINNWRPITIGSIILRLFSRILTARLAKACPINPQQKGFIRSVGC AENLKLLQLLIKNAKKEHRPLGVVFIDLAKAFDTVSHYHLIAVLKRKGVNHQIITLITNMYQ NTRTRIAMKNEQSDPIGIQIGVKQGDPMSPLLFNLSVDPLLCKLEEEGRRYHHGSKCVTSMA FADDLVLLSGSWEGMQSNIKILEAFCNLTGLRTQGEKCHGFYIQPTKDSYTINDCPPWQING APLNMIEPGSSEKYLGLRI 118 (30) R2HalLeu 5'UTR ACGGGATCATAGTTACTAACTGGGCAGAGCTGCAGAGGTTACACCTCCTCGTGGTCCCGCTG GATGCCCTTCGGGGTAACCAAGTTAACCTCTGCCCCAGTGTGGGAATTATAGCTACTTCCCC CCTATCGTCTGGCCTCACCAACCATTCGATAGATTCGACTTGGTGATCTAAATTCCTGGCAC CGATTCCTTGTCGCTGCCCAAAGCCTCGCCTACGGGCACAGTTGGGCTCAGTCACACAGCAC TTGAGGGGGTGTTGTTTGACTTAGACTACTCCTCTATCTGGACTGGCAAA 119 (30) R2HalLeu 3'UTR TCATCTGTTACTGTTCTGTTTTATATCGTTTTTTGCTGTATTACTACTTACTGCTTTTGTTG TATTTACTGTTCTGCCTTATATTGTCTTTGCTGCATTACCACTTATTGTTTTGCTGTATTAC TACTTAATTCTTTAATAT^AACTACCCCTGGTACTCCTGCTCTCTTACCCTGGCACTGGAAAG GTCGGGATAGTAT^ATTGGT^ACTCGTGTTCATGACGTGTCACGCTT^ACCTTVYATTTGGACT^A AT AT T AAT T GGAAT T GT CAAAAT T T TT AC C AAT T T GGAC C AC T T T AC C GGATT T GACAC AGG TGGACGGGCCACCTTTACTTAACTCGGAAAAGAAACATATATATTTTTATGTGTTTGTTAAA 120 (31) R2AqCh ORF MGRPMRISFVSVATQTSPLDLRDNVVSCPTKDHGGLLEIRFEIRGLEFVNSDLVGLEGQQSS TLLDCLALLPEVYEVSNSLSLRDKNICPTPVEEENEEEEESSPLGAAARISPLPSTPVARSR DDLPAEGTPWKIPDKNTACPCCGIVAGKLSGLIEHLKRAHGKKKISFQCARCGRTDVRHHS IACHFPKCKGLVEASPERGWKCEVCEKTFETKIGLGQHKRLVHPVTRNLERISAARPNAGTM 121 RGAHRRCWTEDEVELLRKLDKQYEGQKNINKLIAEHIPTKTTKQISDKRRDLHKSPVKKGKD QAREKHLELKGEYPEEGEHLVCAGS KTEGGLRS CYRKTISEWVTS GKLSILHAMFEQVIEGK EDLTTVTEKATEDCFACLAFKSSELKAGQGRSHQVAQIARPSEPPKEWMKKRAVKRGQFLRF QRLFYLDRGKLAGIILDDVESLKCGIPQDEIHDVFKSRWESPGTFKGLGAFRSRGQADNSAF EAMITAKEISKNIKEMNKNSAPGPDRLSLRDIIKIDPHFVQLMEVFNLWLVTGWPDMVKEC RTVLISKSSLPERI.MDINNWRPITIGSIILRLFSRILTARLAKACPINPRQKGFIRSAGCAE NLKLLQLLIKNAKKEHRPLGWFIDLAKAFDTVSHYHLIAVLKQKGVDHHIITLITNMYQNI KTRIAVKNEQSDPIGIQIGVKQGDPMSPLLFNLSVDPLLCKLEEEGNGYHHGSKRVTSMAFA DDLVLLSGSWEGMQSNIKILEAFCDLTGLRTQGEKCHGFYIQPTKDSYTINDCPPWQVNGTP LNMIEPGSSEKYLGLRIDPWTGISKPELLLKIRDWLQRIGEAPLKPFQKVDILKGYTIPRLI YLADQADVKPTYLEELDLTIRTTVKEWLHLPPCTCDAILYSSTRDGGLGITRLSGLIPSIQA RRLHRIAQSSDEVIRSIVKQEGIEKEFEKLWLTAGGDRNKIPSIWDPSAIRVTSEELGDDEV VSEWEVPTPKTIFPKPCDWRKQEFINWTKLQSQGRGITNFEKDKISNNWLERYRGIPHRKLL TALQLRANVYPTREFLARGRQESQIKSCRHCQAANKS SANI IGYCPAVQDASIKRHNQLCDL IITEVKKKDWIVFQEPILKDERNEIYKPDLVFVNGDQAMVIDITIRYESKLSSLADAAAEKV KKYGHLKSRINELMNAKNIKFKGFPVGARGKWYSGNYKVLKALGISNSRQEKIARCISRKAL FTSVDIVRMFASHSRSIVRT (31) R2AqCh RT ECRTVLISKSSLPERLMDINNWRPITIGSIILRLFSRILTARLAKACPINPRQKGFIRSAGC AENLKLLQLLIKNAKKEHRPLGVVFIDLAKAFDTVSHYHLIAVLKQKGVDHHIITLITNMYQ NIKTRIAVKNEQSDPIGIQIGVKQGDPMSPLLFNLSVDPLLCKLEEEGNGYHHGSKRVTSMA FADDLVLLSGSWEGMQSNIKILEAFCDLTGLRTQGEKCHGFYIQPTKDSYTINDCPPWQVNG TPLNMIEPGSSEKYLGLRI 122 (31) R2AqCh 5'UTR ACGGGATCATAGTTACTAACTGGGCTGAGCTGCAGAGGTTACACCTCCTCGTGGTCCCGCTG GATGCCCTTCGGGGTAACCAAGTTAACCTCTGCCCCAGTGTGGGAATTATAGCTACTTCCCC CCTATCGTCTGGCCTCACCAACCATTCGATAGATTTGATTTGGTGATTCAAATTCCTGGCAC CGATTTCTCGTCGCTGCCCAAAGCCTCGCCTACGGGCATAGTTGGGCTCAGTCATACGACAG TTGAGGGGGTGTTGTTTGACTTATATTACTCCTCTAACTGGACTGGCAAA 123 (31) R2AqCh 3'UTR TCATCTGTTACTGTTCTGTTTTATATTGGTTTTTGCTGTATTACTACTTACTGCTTTTGTTG TATTTACTGTTCTGCCTTATATTGTCTTTGCTGCAGTACCACTTATTGCTTTGCTGTATTAC TACTTAATTCTTTAATAAAACTACCCCTGGTACTCCTGCTCTCTTACCCTGGCACTGGAAAG GTCGGGATAGTAAATTGGAACTCATATTCATGACGTGTCACACTAACCTAAATTTGGACAAA ATATTAATTGGAAATGTCAAAATTTTTACCAATTTGGACCACTTTACCGGATTTGACACAGG T GGAC GGGC C AC C T T TACT T AAC T C GGAAAAGAAAC AT AT AT AAT T T T TAT GT GT T T GT T AA A 124 (32) R2HarHar ORF MGRPMRISFVSVATQTSPLDLRDNVVSCSTKDHGELLEVRLEIRGLEFVNSDWVGPEGQQSS TLIDRLALFPEVYEVSNSLSLRDKNICPTPGESENEEEEESSPLGATARISPLPSTPVSRPR DDLPAEGTPWKVPDKNTSCPCCGNVTGKLSGLIEHLKRAHGKKKILFQCARCGRTDVRHHS IACHFPKCKGLVEASPERSWKCEVCEKTFETKIGLGQHKRLVHPVTRNLERITAARPKAGTM RGAHRRCWTEDEIELLRKLDKQYEGQKNINKLIAEHIPTKTAKQISDKRRDLHKSPVKKKGK ELGRKEHLELEGEHLAEGENLVCVGSEMEGGLRSRYRKTISEWVTSGKLSILHEMFEQVIEG EEDLTTVADKAMKDCFACLAFKSSELKAGQDRPRQVAQTARPSEPPKGWMKKRAVKRGQFLR FQRLFYLDRGKLAGIILDDVESLKCGIPQDEIHGVFKSRWESPGTFKGLGAFRSRGQADNSA FEAMITAKEISKNIKEMNKNSAPGPDRLSLRDIIKIDPHFAQLMEVFNLWLVTGVVPDVVKE CRTVLISKSSLPERQMDINNWRPITIGSIILRLFSRILTARLAKACPIHPRQKGFIRSAGCA ENLKLLQLLIKNAKKDHRPLGWFIDLAKAFDTVSHHHLIAVLKQKGVDHHIITLITNMYQN IKTRIAMKNEQSDPIGIQIGVKQGDPMSPLLFNLSVDPLLCKLEEEGNGYHHGSKCVTSMAF ADDLVLLSGSWEGMQSNIKILEAFCGLTGLRTQGEKCHGFYIQPTKDSYTINDCPPWQINGT PLNMIEPGSSEKYLGLRIDPWTGISKPELLMKIRDWLQRIGEAPLKPFQKVDILKGYTIPRL IYLADQADVKATYLEELDLTIRTTVKDWLHLPPSTCDAILYSSTRDGGLGITRLSGLIPSIQ ARRLHRIAQSSDEVIRSIMKQEGIEKEFEKLWVTAGGDKNKIPSIWDPSAIRVTSEELGDDE FVSEWEVPAPKTIFPKPCDWRKQEFINWTKLQSQGRGIANFEKDKISNNWLDRYRGIPHRKL LTALQLRANVYPTREFLARGRQESQIKSCRHCQAENESSAHIIGYCPAVQDARIKRHNQLCD LLITEVKRKDWWFQEPILKDEQNEIYKPDLVFVKGDQALVIDVTIRYESKLSSLADAAAEK VKKYGHLKSQIQELTNAKNIKFKGFPVGARGKWYSGNYEVLKALGISNSRQDKIARCMSRKA L FT SVDIVHMFAS QS RSIVRT 125 (32) R2HarHar RT ECRTVLISKSSLPERQMDINNWRPITIGSIILRLFSRILTARLAKACPIHPRQKGFIRSAGC AENLKLLQLLIKNAKKDHRPLGVVFIDLAKAFDTVSHHHLIAVLKQKGVDHHIITLITNMYQ NIKTRIAMKNEQSDPIGIQIGVKQGDPMSPLLFNLSVDPLLCKLEEEGNGYHHGSKCVTSMA FADDLVLLSGSWEGMQSNIKILEAFCGLTGLRTQGEKCHGFYIQPTKDSYTINDCPPWQING TPLNMIEPGSSEKYLGLRI 126 (32) R2HarHar 5'UTR ACGGGATCATAGTTACTAACTGGGCAGAGCTGCAGAGGTTACACCTCCTCGTGGTCCCGCTG GATGCCCTTCGGGGTAACCAAGTTAACCTCTGCCCCAGTGTGGGAATTATAGCTACTTCCCC CCTATCGTCTGGCCTCACCAACCATTCGATAGACTCTATTGGGTGATCTAAATTCCTGGCAC 127 CGATTCTTGATCGCTGCCCAAAGCCTCGCCCACGGGCACAGTTGGGCTCAGTCATACAGCAC TTGAGGGGGTGTTGTTTGACTTATACTACTCCTCTATCTGGACTGGCAAA (32) R2HarHar 3'UTR TCACCTGTTACTGTTCTGTTTTTTATATCGGGTTTGCTATACTATTACGTGTTGTTCTTATT GTATTTACTGTTCTGTCTTATGTTGTCTTTGCTGTATTATCAGTTATTGCTTTGCTGTATTA CTACTCAATTCTTTAATAAAACTACCCCTGGTACTCCTGCTCTGTTACCTTGGCACTGGAAA GGTCGGGATAGTAAATTGGAACTCGTTTTCATGACGTGTCACACCAACCTAAATTTGGACAA AATACTAATTGGAAATGTCAAAATTTTACCAATTTGGACCATTTTACCGGATTTGACACAGG TGGACGGGCCACCTTTACTTAACTCGGAAAAGAAACATATATAATTTTTATGTGTTTGTTAA A 128 (33) R2CorAlt ORF MGRPLKLLYVSTATQTDSKDWKPVETEINKTSTPIITSQEIDLQQLEFASSKEIENWQATQS LKQGDNLMTFPEPYESLTPDSVRGNEINATDNDNESNRGEDDSFILATESILDSQKDQTPEE IPLVKLPDKNPSCPCCKTKISGVQRLVEHLLRLHGKRKIIFQCNKCGLQSDNYRSTVCHYPL CKGPKEMVTPGEWICEECERSFQSKIGLGQHKRLSHPEVRNQERIAATRPKVRTARASARKC WSKEEEELLESLLKRYEGERYINKLIAEHIPSKTMKQISDKRRYMIPVQKERKDQEAHVQVE RRKELVTSVETSTQDQLRAHYVTKIEKGIRSRKIKNYPRAFQKIVEGTTDVHAIINDITKEW YGHLEARCQMDKISNKKPRRGQNQDTQSKRKATKWMKKRAIKRGQYLRFQKLFYKDRGKLAR IILDNIESVKCEIPLPEVYSVFKSRWESTGGFKGLGKFRSKGMADNSAFKAMITEKEIIKNI NEINKKAAPGPDGITIKDLTKMDPNYSQTTEIFNLWLTSGKIPDMIRGCRTILLPKSTKPDR LKDINNWRPITIGSVILRLFSRILTARLAKACPINPRQRGFIKSPGCSENLKLLQLLIKNAK RERKELGWFVDIAKAFDTVSHEHIITGLKQKGVDAHIIDLITNMYENSYTQIGTKNEQSDP IQIKVGVKQGDPMSPLLFNLAMDPLLCELEQYGKGFHHRDNSITAMAFADDLVLLSGSWEGM KENIKILETFCDLTGLKTQGEKCHGFFIKPTRDAYTINDCPPWTIGNTPIiNMVCPGSSEKYL GLQIDPWIQIAKPDVTSRIESWLDRITQAPLKPFQRVDILKTYAIPRVIYLADHAEIKAGFL EALDLKIRATVKKWLHLPANTCDAILYSSIKDGGLGITKLQALIPSVQARRLHRLAQCSDNT LRTVLQEENITKTYEKLWITAGGDKDKIPNIWTTKPMVEISTLGEEETSEWEVSTPRNIYPR PCNWKKKEFQKWTQLQSQGIGISNFEGDTISNSWIKNYKGIPHRKLLTALQLRANVYPTREY LARGQKEAYIRSCRHCQAGNESCAHIIGQCPWKDARIKRHNYICGMLVKEAKKKDWVYQE PNIRDRDGELFKPDLIFVKDKQALVVDVTVRYEADDTTLEKAEKEKVKKYQHLEKEVQNLTN TDKVTFMGFPLGARGKWYTKNFDLLQTLGLSASKWERTARALASRALLTSVDIIHMFASKSS HSSVS 129 (33) R2CorAlt RT GCRTILLPKSTKPDRLKDINNWRPITIGSVILRLFSRILTARLAKACPINPRQRGFIKSPGC SENLKLLQLLIKNAKRERKELGVVFVDIAKAFDTVSHEHIITGLKQKGVDAHIIDLITNMYE NSYTQIGTKNEQSDPIQIKVGVKQGDPMSPLLFNLAMDPLLCELEQYGKGFHHRDNSITAMA FADDLVLLSGSWEGMKENIKILETFCDLTGLKTQGEKCHGFFIKPTRDAYTINDCPPWTIGN TPLNMVCPGSSEKYLGLQI 130 (33) R2CorAlt 5'UTR AAGAGTATAGTTACTAACTGGGCTTAGCTGCAGAGATCGCACCTCCCCGTGGTCCCGCTGGA TGCCCTTTAAGGGTAACTGAGCCGATCTCTGCCCCAGTCCGGAGAAGAGGTTACACACCTCT T T C T C C C TAT C GT C T GGAT T C AC T ACC C AGC GAT AGT AAT T T AAAAT AGT GAT AC AC AATC A TTTTGGTATTAACTTATAAGAGTTAACTACCCAGTGCCTTGCCCACAGGTTAAAAGTTGGGC ATAGGTTGACAGATATTGAGGGGTACTGTTAACCTTATTCTCCCTCACTTGGACTGACAAAT TAC C GGAT T T GACACA 131 (33) R2CorAlt 3'UTR TTCATTTTGTTGTTATCTGTTAGAACTCACTGTTATTTACTCATGTATACTGTCTCTTTATC ATATTTTATTGTCTTATTGATGTTATTAGATTTTCACCTGTAGTTTACTAGACTTTTACTGT TATTAAAGCTGTGGTACCTATTATGTCCCTATACCCCGAATGTGGTGAATCTCGTAATGATT AC T T C C C GC GC T C AC T T GAC AT GAC GAT GGT GGAC GGGC C AC C C C T AAC C C GGAAAAGGT AC ATACAC T T T GT GT AT GT TC GT T T AA 132 (34) R2GopFla ORF MMAALASAQLRPSRRANSTILDTEIVPWGRCISRPFEPPMRYHVKVSTVATQTDSPGTTDGV ALRRRESTQTLLTAGEMYPIPGTSQTSFTDGVTSGNTFAQTEVEEPLPPLPMEILNSVFGET VRPGTSPRPCVPTTPASEKEGDTEGSATLAENIDNSCVPTDASTVTTTEGDGETRAQGKVLV PLPHDNPSCPFCGDHVGKPTALNVHLKRHHGGKDVAFQCALCGKIDPNPHSILCHIPKCKGL TLQVPAGDWACEVCAKQFSTKSGLSQHKRRAHPWRNTERILASQPKQNSQRGKHKSCWSAD EELLLLDFDKMYSGDRCINKRIAEAIGTKTAKQVSEKRRLLNLYPRATSVTADQGPGASPHY LEARSDAPSPIKGLHSIYMRKVQQRLSKEQQGQQHKGQEKLESEILSAWVAGDPNVRSLVEA ASIDVLSSFLAPESGTTKKRARAKVSKPKSGKGKSWMKKRAAKRSTYMRFQHLFENDRCKLA SIILDGTERLQCQIPLAEVFQAYKQKWETQTAFQGLGQFKSQTRADNSAFDLLISAKEVIKN IKEMNKNSAPGPDKVSVKDLVRVDPEGDILAGLFNTWLVTGIIPDGIKTCRSLLIPKTMDPE ALKDLGSWRPLTIGSIVLRLFSRILTNRLAKACPLNERQRGFIAAPGCSENLKVLHTIMKQA KRDKKPLGWFIDIAKAFDSVSHKHIMWVLQQRGLDQHVINIICDSYRNVHTRMEIGKELTE PIAIE VGVKQGDPMS PLLFNLA1DPLIS TLEMAGKGF S VGTHKVTALAFADDLVMLSD SWE G MNANIRILESFCTLSGLKVQAKKCHGFQINPTHDSFTINNCEAWKIGATPLNMIIPGESEKY LGVKVDPWIGFTKPALSEKLDTWLERINRAPLKPSQKLAMLNTFTVPRVIYLADHTDCKQAL L S S LDDKIRRAVKEWLHLPADTCNGLLYARS RDGGLGVTRLAS LIPSIQARRLHRIAHS EDA TIRSIALANDIESEYRKLWLVAGGTQDTMPAITDAVIVDHKLPQHVLDKLTEWEKPAPRVIY 133 PIPCNWRNAEFSQWKDLPCQGSGVSHFENDPTSNDWLTHHKGFSERQFLTALKLRANVYPTR EYLGRGKTNSIVRCRHCSAPYESLSHILGQCPAVQGARIRRHNKLCEILMREARKLRWEIYQ EPHLRTAQNELRKPDLIFAREGTALWDVTVRFEYKDKTFSDAAAEKVRHYQSLTEEIRKLT GANKVSYFGLPLGARGKWPVINDRVLSALGLSVSAKGRAARLLSRRALLYTTDVINTFESIG KGFSTPAETKPDGTPKRQKGIS (34) R2GopFla RT TCRSLLIPKTMDPEALKDLGSWRPLTIGSIVLRLFSRILTNRLAKACPLNERQRGFIAAPGC SENLKVLHTIMKQAKRDKKPLGVVFIDIAKAFDSVSHKHIMWVLQQRGLDQHVINIICDSYR WHTRMEIGKELTEPIAIEVGVKQGDPMSPLLFNLALDPLISTLEMAGKGFSVGTHKVTALA FADDLVMLSDSWEGMNANTRTLESFCTLSGLKVQAKKCHGFQINPTHDSFTTNNCEAWKTGA TPLNMIIPGESEKYLGVKV 134 (34) R2GopFla 5'UTR CGCTGTGTCAAGAGTCTGGTTGCTGGGCCGCAGTCCTGAGATCTCAACCTCCCCGTGGTCCC GCTGGACAACTCTCTGGGAGCCTCGATTTTGGGAGTTGACTGACTGAGACTCGGCTGCTTTC GATCCTCCTGCCCTACTGTTCTGGTGCACCGGCTAGGCAGTAGAACCCTACGGTGAAAAATT CA 135 (34) R2GopFla 3'UTR TGATTACATTCATACTAATTCATGATCGCGATCACTGGACAAGGCAACCAGGGTTGGACGGG C C AC C C GGGGT T T GGAACAC C C C AAAT AAC T C GAAAC AGAAAC C C GC GT GGGT T T GT T AAA 136 (35) R2MelCri ORF MAKIPDPFLGGGVWGPPVRLSRVSVGTQTSPADWVDLVSRALPGTKSISQGVDLVSLFPRHW VDLLSKTDQVDLVSQNCLTSKTTNLAENELDLLVNFCLEVYRSDLHEHVHEGVHFSVDWEVL GGLPEVYEQLAPQPCVGDNLDPSPPQDSEPFVLGEGSGKEVSEGTPEALPPVPGEHGGQSPD NIVKVTVPDKNPPCPCCGTRVNSVLSLIEHLKGSHGKKRVCFRCAKCGKENINYHSVICHFP KCRGPEIGKVPAGEWICEVCGRDFATKIGLGQHKRHMHAVERNQERIVASQPKETSNRGAHK RCWTKEEEELLIKLVEQFEGNKNINKLIAEHITTKTAKQISDKRRLLPKKLTTDGADKEPGM SLRPRRAAGGVGTEPGSSQQAQAGAEDNGPGKNHLPGRPAAGGKTMEKIRRPADKDNGRQKT SGQQREGQLQAHYHKTIKESLSAGAINNFPRAFKQLMDGQEMQTMVNQAAQDCFGCLESISQ IRTATRGKKDNLGTHEKQPKKPFQRWMKTRAIEKGNYLRFQRLFHLDRGKLAKIILDDIECL SCDIPPSEIYSVFKARWETPGNFAGLGDFEIKGKADNSAFRDLITAKEIERNVQEMSKGSAP GPDGITLGDIRKMDPGYSRTAELFNLWLTSGEIPDMVRGCRTVLIPKSTQPERLKDINNWRP ITIGSILLRLFSRIVTARMSKACPLNPRQRGFIRAAGCSENLKLLQTIIRTAKSEHRPLGW FVDIAKAFDTVSHQHIIHALQQRGVDPHIIGLVNNMYKDISTYVTTKRNTQTDKIQIRVGVK QGDPLSPLLFNLAMDPLLCKLEERGKGFHRGQRSITAMAFADDLVLLSDSWENMKTNIKILE TFCDLTGLKTQGQKCHGFYIKPTKDSYTINNCAAWTINGTPUSTMINPGESEKYLGLQFDPWT GIAKTNLTTKLEFWLERIDQAPLKPLQKLDILKTYTIPRLTYLADHTEMKAGALEALDQKIR TAVKDWLHLPS CTCDAILYS S TKDGGLGVTKLAGLIPSVQARRLHRIAQS S DETMKEFLEKH QMEQLYKKLWIQAGGESEKMPSIWEALPATVPSNSADTTSEWEAPTLKTKFPKPCDWRRKEF EKWTKLVSQGRGIKNFEGDKISNDWLQYYRRIPHRKLLTALQLRANVYPTREFLSRGREENY IKACRHCNADNETCAHIIGYCPVTQDARIKRHNHICDVLIEEAKKKDWVVFKEPHIRDTIKE LYKPDLTFLKDGRAFWDVTVRYEASKTSLEEAAAEKVNKYKHLGSEVRNLTNAKDVVFMGF PLGARGKWYEGNFELLETLGLSKSRQVRVAKTLSTAALLSSVDIVHMFASRARRLHDAG 137 (35) R2MelCri RT GCRTVLIPKSTQPERLKDINNWRPITIGSILLRLFSRIVTARMSKACPLNPRQRGFIRAAGC SENLKLLQTIIRTAKSEHRPLGVVFVDIAKAFDTVSHQHIIHALQQRGVDPHIIGLVNNMYK DISTYVTTKRNTQTDKIQIRVGVKQGDPLSPLLFNLAMDPLLCKLEERGKGFHRGQRSITAM AFADDLVLLSDSWENMKTNIKILETFCDLTGLKTQGQKCHGFYIKPTKDSYTINNCAAWTIN GTPLNMINPGESEKYLGLQF 138 (35) R2MelCri 5'UTR CGGCTTTGGAGAGTGTAGTTACAAACTGGGCATCGCTGCAGAGATCGCACCTCCTCGTGGTC CCGCTGGTAGCCCTGCGTAGGGTGACTAAGTCGATCTCTGCCCCAGGTACGGAGCCGTTGGG GCTCACCAGCCCAACGAACTCCTGCCAAATTCGGTGAAACAAATTCCTCGGTAAAAGCCGCG TGGCTTATTGCCTGAAACCTGGCCCCCCGGTTTCAGTCAGGGGCAAAGAGTTCGGAAGTGGA CTGACCACCCACTCCGTTCTCACCGTCGAATGTGGTCCCAATTCG 139 (35) R2MelCri 3'UTR TGAATTTTTTAACATTTTATTTTTATTTTTACTTTTATTTTTATTTGTTTATCTTTTATGTT TTAATTTTTATTTTTATTTTTTCATTCTTTGTAGTTTTTCAGTATTGTTTTTGTATGTTTTA ATAAATTAGACGGTAGCTAGGTTCGTAAGGCAGCCACAAGCCAGTTAGGTAGCTCATAGTGA GTAGGGACAGAAAACTTTAATTCATAACGCGTCAATTACCATCTGATTCGGACCAAATAACC GGATTTGGACCAATTTACCGGATTTGTCCAAGGTGGACGGGCCACCTTTACTTAACCCGGAA AAGGAGC AT AT AT TAT T TAT AT GT GTT C GAAAT A 140 (36) R2MyCa ORF MGLLMRLMHVSTATQTNINDLKPVTTKLSETITPVTLPSDDIELCQLEFSNSNEIEDWQTTK FVDQREKLALYPEVYESLPSDSVRENNIILSGNDIDADGEGEDSFALATEFVLDSQKDNLPG ETPLVKLPDKTPSCPCCKIKIMGIEKLVDHLLRSHGKRKIIFQCVTCGLQNENYRSIVCHYP LCKGASEVIPSGDCVCEECGRSFQTKRGLGQHKRHAHPEVRNQERIDAARLKVKTSREPARK CWSKEEEELLEKLVQQYEGERCINKLIAEHIPTKTLKQISDKRRCMKPVRKEKEDQEICVQV AKRKNQPAVTETSNPDQLRAHYVETIKKGIKLRTINIYPRAFRKIVEGSKDQLTLVNDTTED WYGHLKARCQAERKIKVGSKKKKAQETQSKRKATNWMKKRAIKKGQYLRYQKLFYKDRGKLA NIILDEIESVKCEIPLSEVFSVFKSKWETTGKFKGLGHFQSKGMADNSAFEVMITEKEVAKN 141 IKEANKNAAPGPDGIIMKDLIKMDSKYTEITELFNLWLTSGKIPDSLRRCRTILIPKSTKPD RUTDINNWRPITIGSAVLRLFSKILTARLEKACPINLRQRGFIKSPGCSENLKLLELIIRNA KKQHRELGWFVDIAKAFDTVSHQHIIMGLKQKGVDSHIINLIANMYENIYTEIGTKEEKSE PIQIKVGVKQGDPMSPILFNLAMDPLLCELEQYGKEYHYDTKS ITAMAFADDLVLLSDS'WEG MKENIEILEVFCDLTGLKTQGEKCHGFFIKPTKDSYTINDCPPWTVGGTPLNMICPGSSEKY LGLHIDPWMQIAKPDLSSKIDTWLDRISESPLKPLQKVDILKIYMIPRIIYLADHTEIKTGF LEALDLKLRARVKKWLHLPNDTCDAIFYSSMKDGGLGIIKLQSLIPSVQARRIHRLAQSSDE TLRDILQQENISQKYEKLWITAGGDKDQIPDIWAPKPTVQTSYLGEEDTSEWEVTTSKNTYP RPCWRKTEFRKWTKLQSQGIGIVNFEGDTISNSWIKNYRGIPHRKLLTALKLRANVYPTRE YLARGKKDGWTTSCRHCKAENESCAHVIGQCPAVKDARIKRHNYICEMLLNEARRKDWVVYQ EPNIRDSDGELFKPDLVFVKEKQALWDVTVRYEGDVNTLEKAAKEKVKKYQHLEKEIQELT NTEKVIFVGFPLGARGKWFNKNFDLLQTLGLSSSRRERVARAMASRALLTSVDIMHIFTSKV RTAINK (36) R2MyCa RT RCRTILIPKSTKPDRLNDINNWRPITIGSAVLRLFSKILTARLEKACPINLRQRGFIKSPGC SENLKLLELIIRNAKKQHRELGVVFVDIAKAFDTVSHQHIIMGLKQKGVDSHIINLIANMYE NIYTEIGTKEEKSEPIQIKVGVKQGDPMSPILFNLAMDPLLCELEQYGKEYHYDTKSITAMA FADDLVLLSDSWEGMKENIEILEVFCDLTGLKTQGEKCHGFFIKPTKDSYTINDCPPWTVGG TPLNMICPGSSEKYLGLHI 142 (36) R2MyCa 5'UTR TGAGAGCATAGTTACAAACTGGGCTCAGCTGCAGAGGTCGCACCTCCACGTGGTCCCGCTGG ATGCCCCTTGTGGGTAACTAAGTCGACCTACTGCCCCAGTTCGGAGGAGGGGTTTTGGCCTC TCTCTCCC TAT C GT C T GGAGT C AC T GC C C AGC GAT AGT AT T C AAAAAC AGT GAT AC AAATT T TTTTTTGGTAATAGCTTACGAAGCAAATTACCCAAGCACCTTGCTCACGGGTTCTAGTTGAG CACAGGTTGACAGATATTGAGGGATACTGTTGACCTTATACCCCCTCACTTGAATTGGCAAT TAT AT AT AC C GC AAG 143 (36) R2MyCa 3'UTR GTAATCTTTTATTGTTTTATTGTTATTATAGTATTTTAGTTTTTATAGTTTTAATGTTTAGA TATGTTATGTTTTTATTTCTTTTATTGTGTGGTTATGTTATAGTTTTAAAGTTCTTATTAAA GGCTGTGCGTTTTAACCCCCTTCCCCCCAGTGGAGAATCTCGTGATGATTACACTCTAAGCG C GAT C AC C GGAC AT GAC GAT GGT GGAC GGGC C AC C GT T AC T T AAC C C GT AAAAGGGAC AC AC T C T GT GT GT GT T C GT ATAA 144 (37) R2PoAt ORF MVKALKLLRVSTATQTNFKDWHIKSPQKLNFKPSEPGREVWKSLKLEFYNSLHCSEECTAHC LGREGLEGYPEVYVEETMACLSLNDNGTGESQEKITTPITAQEEVTALSEPEETTIQPQNNG ESEDCPVISVPDKNPPCPRCGMIMNKMHGLIEHLLRAHGIRECKFKCTKCDLENTNFHRIAC HYPKCKGKAKEPPPGKWPCDVCQMSFQTKIGLGQHKRIAHPAVRNQERIEATKPKETSARGA HKKCWSEEEENLLIQLIKQYEGNENINKLIAEHIPSKTAKQINDKRRCLVSKQPAPFGLQLR GKTQEQPQEKTRKPPKRKETTINQLKKHYEKMIPSKISDGTFIVYKEAFQEILKKKNKNPAH TISEITKDCIKVFKGMHSQEKNTRKPKQGHSQPKRRQAAKWMSKRAIKKGQYLRFQKLFYTD RGKLARIVLDDVEGLKCQIPANEISSVFRERWETPGNFKGFEDFEAEGTTDNTKFLPLITAK EIDKNIKEMAKTSAPGPDDITLGDLCKADPKFSLLTEIFNLWLTSGTVPDQVKNCRTVLLPK SDRPDRLKDINNWRPITIGS TVLRLFSRVLTARLS KACPINPRQKGFTRAPGC SENLQLLQL LLKTAKREHNEIAWFVDIAKAFDTVSHQHIIESLRQRKVDEHIINLIQSMYVNTSTCIKTQ DETSAPINILKGVKQGDPMSPLLFNLAWPLLCKLEKEGQGYKCEDAKITAMAFADDLVLLS DSWEGMMHNIKILETFCDITGLKTQGEKCHGFYIKPTKESYTINDCPPWTVNNTPLNMIPPG ESEKYLGLQVDPWGIAQAELLAKTNTWLERIGRTKLKPLQKVDLLKMYTIPRLYYIADHTD TPFVLLKNIDQAVRTKVKEWLHLPACTCDALLYSSTRDGGLGISRLEGLIPSIQARRLHRLA QSKDEILTNLLKGEGADLRHKKLWVKAGGDKTKIPSIWTTRPTVAVQAPTSENLSEWEVPTA KLKYPKPCNLRKKEFEKWKQLVSQGRGITHFENDSISNAWLTSYRAIHHRKLITALQLRANV YPTREFLARGRGGQYIKSCRHCNAENETCSHIIGKCPVTQDARIQRHNKICDLLTNIAQRKD WTVFHEPHIRDSNGQLFKPDLIFVKDNQAQVVDVTVRYESEESTLENAAEEKVSKYQHLEKE IQELTNAQQVTFIGFPLGSRGKWYPGNSMLLETLGLSKREQDRTSKTLASRALESSVDIIHI FASKTRTPG 145 (37) R2PoAt RT NCRTVLLPKSDRPDRLKDINNWRPITIGSTVLRLFSRVLTARLSKACPINPRQKGFTRAPGC SENLQLLQLLLKTAKREHNEIAVVFVDIAKAFDTVSHQHIIESLRQRKVDEHIINLIQSMYV NTSTCIKTQDETSAPINILKGVKQGDPMSPLLFNLALDPLLCKLEKEGQGYKCEDAKITAMA FADDLVLLSDSWEGMMHNIKILETFCDITGLKTQGEKCHGFYIKPTKESYTINDCPPWTVNN TPLNMIPPGESEKYLGLQV 146 (37) R2PoAt 5'UTR CAGAGGTAAGTCAGAGTTACTAACTGGGCTTTGCCGCGGAAATCAGACCTCCTCGTGGTCCC GCTGGATACCCGCAAGGGTAACTAACTGATTTCTGCCCCAGTGTGAGCGAGGCTGTGTTTTA CACTGCTTCCCTGCCTTTGGACTCGCCACCCAGAGTGCAGTTTCGCGATTTTGCGTTGAAAA GTTATCGGCAGAAGCTCTTAAAAAGCTCCCTGCCTGAAACCGTGCCCACCGGTAAAGTTGGG CAAAGCTAACAGCGCTTGAGGGGGTACTGTTAGTTAAATCACCCTCAATTGGACTGACTTTA AAC C T AAAAC GGC AC C 147 (37) R2PoAt AT AGT AAAAC T C T GT AT TAGT T AGATT AC AGT T AT T T T T T T T AGGT T AAGC AT AT T T T AGT T AGTTTCTTTCTGTATTAGTTAGTATTGTTGCTGATTAGTTCTTATATGTTTCTTTATATTTT 148 3'UTR TGAATGCTTTTATCACTGTATATACGTTATATTTTTCAATAAAGGTGTGGGAGTAGCTGGAT AGATAGGGAACCCCCACCCCATCCCCCGCCCCCCATTTTCTGTTCCATCCTGAGTGATGGAT GTATCATCCGACATGCGACGTTACACCTAATTTGGCACTAAAATCTCACGTTTGTGACATAG GTGGTCGGACCACCTTTATAAAAACCTTGAATTTGACCTATACCTACCGATTTTGACACAGG TGGACGGGCCACCTATACTTAACCCGGAAAAGGTGCATATACGTTAGTATGTGTTCGTTTAA (38) R2ChPi ORF MMEALASAQLGPGRRANSTHLDTDVVPWGRCTFRTFEPLARYRVKVSTVATQTDSHQLTDNE AYPTLKSSKTTVTEGEMYPIPGTSQTHTAAGAISCETVAQTEAEEILPALPLEILNSAFGET VGPDTSPEPCVPTTPVSEKERDAGGSETLADGTDGTICVPSSAPTWVTEGECENRVQGKVL VTLPHDNPACPFCGDHVGKPKALSVHMKHHHGGKDVEFQCSLCTRADPNVHSILCHIPKCKG LTPQEPAGDWACEVCARRFGTKSGLSQHKRRAHPVVRNAERIQASQPKQNSQRGKHKSCWSA EEELLLTDFDTMYSGEKYINKLIAEAIKTKTAKQVSDKRRLLNLYRKKSSGTADPGPGAQKH NLEVRSETPISTTGLKNSYMRTITNRLRASNRGPLRQDLEKFEAEVLSAWVAGDPNIRSLVE TTSIDVLSSFLAPEHEHKHKQKGNTKGRKSKSGKGQSWRQKRATKRGTYIRFQHLFENDRCK LASIILDGTERLQCEIPLEKVFQTYKDKWESRTPFQGLGQFKSHALADNSAFDILISAKEVL KNISEMNKNSAPGPDKVSLKDLVRVDPEGDTLAGLFNTWLVTGTIPDGIKECRSLLIPKTMD PEALQDLGNWRPLTIGSIVLRLFSRILTNRLAKACPINARQRGFIAAPGCSENLKVLHTITK QAKKEKKPLGWF ID IAKAFD S VSHDHIMWVLQERGLDQHI IN 11GD S YRNVH TRME VGKE L TSPIAIDVGVKQGDPMSPLLFNLALDPLISTLETAGKGFSFGAQKVTALAFADDLVMLSDSW EGMHTNIQILESFCHLSGLKVQAKKCHGFLLSPTHDSFTVNNCEAWKIGADGLNMIAPGESE KYLGLKVDPWIGFSKPALSDKLSTWLERINRAPLKPSQKLEMLNTFTIPRVIYLADHTDCKK TLLSSLDDNIRRAVKEWLHLPADTCNSFLYTRSRDGGLGVTRLASLIPSIQARRLHRIAHSE DMTIRFIALANDIESEYQSLWLAAGGTQDTMPAITDPVTIDHRLPQHALELLNEWERPAPRV IYPIPCNWRDAEFSQWKDLPCQGSGVSHFGNDPTSNSWIKHLTGFSQRQFLTALKLRANVYP TREYLGRGKNEYMVKCRHCDAPYESLSHILGQCPAVQGARIRRHNKICEILTREARKLEWTV YQEPHLRTSTNELRKPDLVFVKDGTALWDVTVRFEYKEQTFSDAAAEKVRHYQSLTSEISR LTGASKVRYFGFPLGARGKWPKINDRVLSALGLSESAQGRAARLLSRRALLYSIDVLNTFSG IGKGLPNSADTKSVGTQREQLGIS 149 (38) R2ChPi RT ECRSLLIPKTMDPEALQDLGNWRPLTIGSIVLRLFSRILTNRLAKACPINARQRGFIAAPGC SENLKVLHTITKQAKKEKKPLGVVFIDIAKAFDSVSHDHIMWVLQERGLDQHIINIIGDSYR NVHTRMEVGKELTSPIAIDVGVKQGDPMSPLLFNLALDPLISTLETAGKGFSFGAQKVTALA FADDLVMLSDSWEGMHTNIQILESFCHLSGLKVQAKKCHGFLLSPTHDSFTVNNCEAWKIGA DGLNMIAPGESEKYLGLKV 150 (38) R2ChPi 5'UTR CTGTGTCAAGAGTTTGGTTGCTGGGCCGCAGTATTGAGATCTCAACCTCCCCGTGGTCCCGC TGGACGACTCTCTGGGATGCCCGTTAGGGAGTTGACTGACTGAGACTCAGCTGCTTTCGTTC CCCTGCCC TAG T GC T C T GGT AC AC C GGC T AGAC AGT AGAAC GC T AC GGT GAAAAAC AC TA 151 (38) R2ChPi 3'UTR ATGATTAAAATCTCAATAATTCATGACCGCGATCACTGGATGGGACTTTCTGGGTTGGATGA GCCACCCGGGGTTTGGAACACCCCAAATAACTCAAAACAAAAACCCGCGTGGGTTTGTAAAA A 152 (39) R2ATLH ORF METTLVSIRAKIQATPLLWANHPLEGFLLVMKRKEMTSPGPSGPQGNSRDNDAVGVPSIPAC PPGDFTCPCGRTFPSKRSLAMHRHHSHPAEVNEERTTRLPLKRLAWSQEDDSALLRHATRLW APSLLKKKHLELLAPLFPGRSVEALKKRLQILKWLPPPPPETVSSPGTTPTMVSPPAFIRSP ETPTIVFPDTPSMVFPDTPTMVFPDTPTVVFPDTPTLDVQETQPPTSSWKVDLLDFAARNLR EPKMGADDLLNITSKLQSGTVSQSEAAHLLNEHAKRWFPHSWAPSKRTHRSLGPAPSNRQLR RANYAAVQKLYHLRKKDAASCVLSGQWKSAHRGSKDTIDGLEDYWSQTFEHPSATDPRDPRT PEDTAWTLLDTITAAEVTSALRDMGNSAAGLDRLTPATLSSWDQPSLAAYFNLILATESVPK HISKSRVIFLPKTDEPTAPSDFRPISISSVILRAFHKILARRITSTLQFSKLQHAFLKRDGC LEAS SLLHAILRKIHEDRTPASLIFLDISKAFD SVSIHTLLRVAKS SGLPPPLTNYLVSLYD HPRVKLEAREVTCGRGVRQGDPLSPLLFIMAFEDILQSALPDIGFDLDGHNIPALAYADDLV LFARRPERLQEKLDILVDSLAAAGMSINAKKSIGLTIAKDGKRKTMVLLPHIYRSGSTEIKP LGPSDVTRYLGLDFTWKGKVSPKHTSKLDQMLLELTRAPLKPYQRLDLLKNFAIPRLTHELV LGNAHRNTLKKLDVLIRSAVRSWLRLPKDTPLGFLHAHIRDGGIGLPCLNTSIPILQRNRFA KLLSNPEPIQKWANQKSFRVIQRITNRPVQIGNHIIQSKKEARTAWKNELRRSVDGRDLFG DPVDPVSHRWVSHPQRVFPRLHLRGIQLRGGLLPTRTRNARGRDPPVTSTSCRGLCGQAETL NHILQVCDKTHDARCARHNRIVHRLSQLLRRKNVPCWIEPIIPAGATYIKPDIIAKVNNELL VMDVSWSGSRLNETWSIKTEKYGSSKSSTALQSWHGSRIPLRHYPIIISNRGLLFAQSGQA LRSIGLSARDLTDICLLTIIGSLKCFDHYTRSTLDL 153 (39) R2ATLH RT KSRVIFLPKTDEPTAPSDFRPISISSVILRAFHKILARRITSTLQFSKLQHAFLKRDGCLEA S SLLHAILRKIHEDRTPASLIFLDISKAFDSVS IHTLLRVAKS SGLPPPLTNYLVSLYD HPR VKLEAREVTCGRGVRQGDPLSPLLFIMAFEDILQSALPDIGFDLDGHNIPALAYADDLVLFA RRPERLQEKLDILVDSLAAAGMSINAKKSIGLTIAKDGKRKTMVLLPHIYRSGSTEIKPLGP SDVTRYLGLDF 154 (39) R2ATLH GAGTTGTAGTTACACGGCCTGGGCGCCTCCTCGTGGCGACCGCTGGAGAAG 155 5'UTR (39) R2ATLH 3'UTR AGCCGGTGTCGCATGTAGGTTACTGGGAACAGCTCATGACCCGCCACAAGCGGCGATCCCCC TGCAACGTCGTTATCATTAGCGGTTATCCGCCTCAAGGCTACCGTTTGCGGTAGTGTAATTG TTACATTGCTGCTGTCGGTTGACCTTGATAATCCATGACACC 156 (40) R2ATLH' ORF MKRKEMTSPGPSGPQGNSRDNDAVGVPSIPACPPGDFTCPCGRTFPSKRSLAMHRHHSHPAE VNEERTTRLPLKRLAWSQEDDSALLRHATRLWAPSLLKKKHLELLAPLFPGRSVEALKKRLQ ILKWLPPPPPETVSSPGTTPTMVSPPAFIRSPETPTIVFPDTPSMVFPDTPTMVFPDTPTVV FPDTPTLDVQETQPPTSSWKVDLLDFAARNLREPKMGADDLLNITSKLQSGTVSQSEAAHLL NEHAKRWFPHSWAPSKRTHRSLGPAPSNRQLRRANYAAVQKLYHLRKKDAASCVLSGQWKSA HRGSKDTIDGLEDYWSQTFEHPSATDPRDPRTPEDTAWTLLDTITAAEVTSALRDMGNSAAG LDRLTPATLSSWDQPSLAAYFNLILATESVPKHISKSRVIFLPKTDEPTAPSDFRPISISSV ILRAFHKILARRITSTLQFSKLQHAFLKRDGCLEASSLLHAILRKIHEDRTPASLIFIiDISK AFDSVSIHTLLRVAKSSGLPPPLTNYLVSLYDHPRVKLEAREVTCGRGVRQGDPLSPLLFIM AFEDILQ S ALPDIGFDLDGHNIPALAYADDLVLFARRPERLQE KLDILVD S LAAAGMSINAK KSIGLTIAKDGKRKTMVLLPHIYRSGSTEIKPLGPSDVTRYLGLDFTWKGKVSPKHTSKLDQ MLLELTRAPLKPYQRLDLLKNFAIPRLTHELVLGNAHRNTLKKLDVLIRSAVRSWLRLPKDT PLGFLHAHIRDGGIGLPCLNTSIPILQRNRFAKLLSNPEPIQKWANQKSFRVIQRITNRPV QIGNHIIQSKKEARTAWKNELRRSVDGRDLFGDPVDPVSHRWVSHPQRVFPRLHLRGIQLRG GLLPTRTRNARGRDPPVTSTSCRGLCGQAETLNHILQVCDKTHDARCARHNRIVHRLSQLLR RKNVPCWIEPIIPAGATYIKPDIIAKVNNELLVMDVSWSGSRLNETWSIKTEKYGSSKSST ALQSWHGSRIPLRHYPIIISNRGLLFAQSGQALRSIGLSARDLTDICLLTIIGSLKCFDHYT RSTLDL 157 (40) R2ATLH' RT KSRVIFLPKTDEPTAPSDFRPISISSVILRAFHKILARRITSTLQFSKLQHAFLKRDGCLEA SSLLHAILRKIHEDRTPASLIFLDISKAFDSVSIHTLLRVAKSSGLPPPLTNYLVSLYDHPR VKLEAREVTCGRGVRQGDPLSPLLFIMAFEDILQSALPDIGFDLDGHNIPALAYADDLVLFA RRPERLQEKLDILVDSLAAAGMSINAKKSIGLTIAKDGKRKTMVLLPHIYRSGSTEIKPLGP SDVTRYLGLDF 158 (40) R2ATLH' 5'UTR GAGTTGTAGTTACACGGCCTGGGCGCCTCCTCGTGGCGACCGCTGGAGAAGATGGAGACGAC TCTCGTCTCCATCCGAGCTAAGATCCAGGCCACCCCCCTCCTCTGGGCTAACCACCCTCTGG AGGGTTTTCTGCTGGTT 159 (40) R2ATLH' 3'UTR AGCCGGTGTCGCATGTAGGTTACTGGGAACAGCTCATGACCCGCCACAAGCGGCGATCCCCC TGCAACGTCGTTATCATTAGCGGTTATCCGCCTCAAGGCTACCGTTTGCGGTAGTGTAATTG TTACATTGCTGCTGTCGGTTGACCTTGATAATCCATGACACC 160 (41) R2ATLH" ORF MTSPGPSGPQGNSRDNDAVGVPSIPACPPGDFTCPCGRTFPSKRSLAMHRHHSHPAEVNEER TTRLPLKRLAWSQEDDSALLRHATRLWAPSLLKKKHLELLAPLFPGRSVEALKKRLQILKWL PPPPPETVSSPGTTPTMVSPPAFIRSPETPTIVFPDTPSMVFPDTPTMVFPDTPTWFPDTP TLDVQETQPPTSSWKVDLLDFAARNLREPKMGADDLLNITSKLQSGTVSQSEAAHLLNEHAK RWFPHSWAPSKRTHRSLGPAPSNRQLRRANYAAVQKLYHLRKKDAASCVLSGQWKSAHRGSK DTIDGLEDYWSQTFEHPSATDPRDPRTPEDTAWTLLDTITAAEVTSALRDMGNSAAGLDRLT PATLSSWDQPSLAAYFNLILATESVPKHISKSRVIFLPKTDEPTAPSDFRPISISSVILRAF HKILARRITSTLQFSKLQHAFLKRDGCLEASSLLHAILRKIHEDRTPASLIFLDISKAFDSV SIHTLLRVAKSSGLPPPLTNYLVSLYDHPRVKLEAREVTCGRGVRQGDPLSPLLFIMAFEDI LQSALPDIGFD WGHNIPALAYADDLVLFARRPERLQEKLDILVDSLAAAGMS INAKKS IGL TIAKDGKRKTMVLLPHIYRSGSTEIKPLGPSDVTRYLGLDFTWKGKVSPKHTSKLDQMLLEL TRAPLKPYQRLDLLKNFAIPRLTHELVLGNAHRNTLKKLDVLIRSAVRSWLRLPKDTPLGFL HAHIRDGGIGLPCLNTSIPILQRNRFAKLLSNPEPIQKVVANQKSFRVIQRITNRPVQIGNH IIQSKKEARTAWKNELRRSVDGRDLFGDPVDPVSHRWVSHPQRVFPRLHLRGIQLRGGLLPT RTRNARGRDPPVTSTSCRGLCGQAETLNHILQVCDKTHDARCARHNRIVHRLSQLLRRKNVP CWIEPIIPAGATYIKPDIIAKVNNELLVMDVSVVSGSRLNETWSIKTEKYGSSKSSTALQSW HGSRIPLRHYPIIISNRGLLFAQSGQALRSIGLSARDLTDICLLTIIGSLKCFDHYTRSTLD L 161 (41) R2ATLH" RT KSRVIFLPKTDEPTAPSDFRPISISSVILRAFHKILARRITSTLQFSKLQHAFLKRDGCLEA SSLLHAILRKIHEDRTPASLIFLDISKAFDSVSIHTLLRVAKSSGLPPPLTNYLVSLYDHPR VKLEAREVTCGRGVRQGDPLSPLLFIMAFEDILQSALPDIGFDLDGHNIPALAYADDLVLFA RRPERLQEKLDILVDSLAAAGMSINAKKSIGLTIAKDGKRKTMVLLPHIYRSGSTEIKPLGP SDVTRYLGLDF 162 (41) R2ATLH" 5'UTR GAGTTGTAGTTACACGGCCTGGGCGCCTCCTCGTGGCGACCGCTGGAGAAGATGGAGACGAC TCTCGTCTCCATCCGAGCTAAGATCCAGGCCACCCCCCTCCTCTGGGCTAACCACCCTCTGG AGGGT TTTCTGCT GGT TAT GAAAAGAAAAGAA 163 (41) R2ATLH" 3'UTR AGCCGGTGTCGCATGTAGGTTACTGGGAACAGCTCATGACCCGCCACAAGCGGCGATCCCCC TGCAACGTCGTTATCATTAGCGGTTATCCGCCTCAAGGCTACCGTTTGCGGTAGTGTAATTG TTACATTGCTGCTGTCGGTTGACCTTGATAATCCATGACACC 164 (42) R2Mac ORF MDLLFYFPGIGKMVRSMRLLRLSAATQTSPSDWEDIPTRNLFNKGLVGEEIELKRLEFYNSC MINNLLGYHPPIRWEGLARYPEVYEVPFPEPDSGDNTSIREAVEENKKNRDDSPTLTSAPIR EKDSGQTPKTPWKVPDKNPPCPCCGNRISGLLGLVDHLKRDHGRRKIRFQCAKCGRENLNC HSIACHFPHCKGPADRAPAGEWTCEVCGRNFQSKIGLGQHKRLTHPEERNRERIAASCPKTK AKPKKTGAHRKCWTSEEEELLIKLMEQYKGKKHINKLIAEHIPSKTTKQISDKRRLLEPGKK NGEDQDLDLLIEDEWEQLAVADSSREGYLQAHYLRKVGDRLSAQTLHTFQGAFKKIIDGQQD PLSWNETSRDCYECLGVSCQLGKTSQNKQKQQNPSQNPRPGKKAKNWMRKRAIRKGQYLRF QRLFHLDKGKIARIILDDLESMRCEIPLQDIHSVFQSRWESPGTFKSLGGFQSKGLADNSAF EAMITAQEVSKNISEMSKNSAPGPDGITLRDLNKMDPKYSLTAEIFNLWLTSGMIPDTVRGC RTVLIPKS S RPERLKDINNWRPITIGS11LRLF SR IL TARL S KAC PINPRQRGFIRAAGC S E NLKLLQLLIQNAKRE HREMGWFVDIAKAFD TVSHQHILMGLKQKGVDPHITNLIKNMYENI YTQIDTKKGTTDQIKMRVGVKQGDPMSPLLFNLAIDPLLCKLEECGNGYQQGKHTITAMAFA DDLVLLSGSWEGMQNNIKILETFCELTGLRTQGEKCHGFYIKPTAKSTYSINDCPAWTVNGT SLNMITPGSSEKYLGLRVDPWVGIAKPGLSQQVEHWLQRLEGAPLKPLQKIDLLKTFAIPKI IYLADHTDTKAGLLESLDLQIRRSVKEWLHLPPCTCDAFLYSSTKDGGLGITRLAGLIPSVQ ARRLHRLAQSSDETIRAVLKEEQIEKDYEKLWVKAGGDKDRMPSIWEPRLVVEPLEHREEGA PSEWEVSAPKIKYPRPCNWRKREFNEWSKLASQGRGIDNFEGDKISNFWIERYRGIPHRKLL TALQLRANVYPSKEFLARGRRDKYSTSCRHCPAENESCSHIIGNCPITQEARIKRHNYICGM LSEQAKKADWAVFQEPNIRDDNNELYKPDLIFVKDDKAYWDVTVRYEHSKKNLEIAAKEKA KKYQHLEKQIQDLTNATKVSFFGFPVGARGKWYDKNFELLSALGLSKSRQEKTARALARRAL FASVDIVHMFASKARTVLVS 165 (42) R2Mac RT GCRTVLIPKSSRPERLKDINNWRPITIGSIILRLFSRILTARLSKACPINPRQRGFIRAAGC S ENLKLLQLLIQNAKREHREMGVVFVDIAKAFDTVSHQHILMGLKQKGVDPHITNLIKNMYE NIYTQIDTKKGTTDQIKMRVGVKQGDPMSPLLFNLAIDPLLCKLEECGNGYQQGKHTITAMA FADDLVLLSGSWEGMQNNIKILETFCELTGLRTQGEKCHGFYIKPTAKSTYSINDCPAWTVN GTSLNMITPGSSEKYLGLRV 166 (42) R2Mac 5'UTR AATGGGAGCATAGTTACTAACTGGGCTTAGCTGCAGAGGTCGCACCTCCTCGTGGTCCCGCT GGATACCCCTAGGGGTAACCGAGTCGACCTCTGCCCCAGTTCGGAGAATTGGCTAGAGCCTC TCTCTCCCTATCGCTTGGACTCGCCAACCAGCGATAGTATTGCTTTGGGTGAAACAAACTTA TGGTAACAGCCCTTACTAGGTCTGTTACCCAGAGCCTTGCCCACTGGCTTTAGCTGGGCACA GTTTGACAGATCCTGAGGGGGTACTGTCGACTTATACAACCCTCAC 167 (42) R2Mac 3'UTR TTCAATAAAGTTGCGACCGCTAGGGACGTAGGATCGCCACAAGCCAGGTAGAAAATTCAGGT AGGATAGTTTGGAGGGACTAGGATCTGGGACTTAACTCATGACGTGTCTTTTACCATCGACT TTGGGACAAATCTTTACCGATTTTGACCGAGGTGGACGGGCCACCTTTACTTAACCCGGAAA AGGGAC AT AT AT T AAT T TAT AT GT GTT C GAAAAA 168 (43) R2Pif ORF MGWLLRLMWVSTGTQTDSRDWKPWPKLNEVSSSLVTTSDEIELQHLEFASSKEIGNWQVTQ ILSQEEKLALFPDVYESSTSDSVRDNENNISDNNNEINGDEDDSFMLATEPALDSQKNRSPG KIPLVRLPDKNPSCPCCKTKIAGVERLIDHLLRSHGIRKTVFQCIKCDLQSDNYRSIVCHYP KCKGAIDMGPSGDWICEVCGRSFQTNRGLGQHKRLSHPEVRNQERIAATRPKERTARESSRK CWSKEEEELLEKLVKQYEGEKYINKLIAEHIPSKTIKQISDKRRHMFPVQKEREDRDGYVQV DKRKRHLEIETPSPDQLRVHYLAMITKGLKSRKMNNYSRVFQKIVEGKPEVHAIINDITIEW YGHLEARCRRRETSDVKMERGQIQGPQSKRKAANWMKKRAIKKGQYLRFQKLFYKDRGKLAR IILDDIESVKCEIPLPEVHSVFKTRWETTGRFKNLGNFRSIGMADNNVFKAMITEKEIIKNI NEMNKNTAPGPDGITVRELIKMDPKFTQITEMFNLWLTSGRIPDIIRECRTVLLPKSTKPDR LKDINNWRPITIGSVILRLFSRILTARLIKACPINPRQRGFIKSPGCSENLKLLQLLMKNAK REHNELGWFVDIAKAFDTINHQHIITGLKQKGVDAHIINLIANMYENIYTRIGINNKQLDP IQINVGVKQGDPMSPLLFNLAMDPLLCELEQYGEGFKFRNKSITAMAFADDLVLLSGSWEGM KRNIEILETFCDLTGLKTQGEKCHGFLIKPTREAYTINDCPPWTIDGTPINMVNPGSSEKYL GVQIDPWIQIAKSDLSSRIETWLCRVSEAPLKPFQKVDMLKTYVIPRIIYLADHTEIKSGSL EALDLKIRMTVKKWLHLPASTCDAILYSSIKDGGLGIIKLQALIPSVQARRLHRLAQGSDDI LRAVLVEENITQMYEKLWISAGGDKEKVPNIWAPKPTVQTATLGEEEISEGENNILKNNYPR PCNWKKKEFQKWTQLQSQGIGITNFEGDTISNNWIKNYRGIPHRKLLTALQLRANVYPTREY LARGKKDGYIRSCRHCQAENESCAHIIGQCPIVKDARIKRHNYICGMLAEEAKMKEWMVYQE PNIRDTDGELFKPDLIFVKDKKALVVDVTIRYEADDTTLDKAAKEKVRKYRHLEKEIKELTN TEKVTFIGFPLGARGKWYNKNFDLLQTLGLSASKRERTARALASRALFTSVDIVHIFASKSS TQLCK 169 (43) R2Pif RT ECRTVLLPKSTKPDRLKDINNWRPITIGSVILRLFSRILTARLIKACPINPRQRGFIKSPGC SENLKLLQLLMKNAKREHNELGVVFVDIAKAFDTINHQHIITGLKQKGVDAHIINLIANMYE NIYTRIGINNKQLDPIQINVGVKQGDPMSPLLFNLAMDPLLCELEQYGEGFKFRNKSITAMA FADDLVLLSGSWEGMKRNIEILETFCDLTGLKTQGEKCHGFLIKPTREAYTINDCPPWTIDG TPINMVNPGSSEKYLGVQI 170 (43) R2Pif 5'UTR CGCGACAGCATAGTTACTAACTGGGCTAAGCTGCAGAGATCGCACCTCCCCGTGGTCCCGCT GGATGCCCGTAAAGGGTAACTAAGTCGATCTCTGCCCCAGTCCGGAGGAGAAGGCCATAACC 171 TCTCTCTCCCTATCGTCTGGACTCACTACCCAGCGATAGTACTCAAAAATAGTGAAACAAAT TTTTGTGGTATTAACTTACCGAGGTTAATTGCCCGAAACCTTGCCCACGGGCTAAAGTTGGG CTCTAGGTTGACAGGTATTGAGGGGTACTGTTAACCTTGACTTCCCTCACTTGTTGGATCTA TTGGTATTGACAA (43) R2Pif 3'UTR TCTCTTCATGTTGTTACTAAGTTTTAGATTTTCTTTGATTTTATCATTTTTTATTGTCTTTT ATTGTCTTTTTAGCCTCTTTTAGTTTTTTAGTAATTATCTGTATTAGGTTTCATCTTACTTT TAATTGTATTAGTTTTATTTGTATTTTATTAGTTGCTATTAAAGCTGTGTTCTTTTATTGTG ACCCTTTCCCCAAAGTGGTGAATCTCGTAATGATTACATCTAGCGCTCACTGGACATGACGA TGGTGGACGGGCCACCTCTAACCCGGAAAAGGTACATACACTCTGTGTGTGTTCGTTTAA 172 (44) R2TyAI ORF MCLAARIAFVSVGTQTSLLDLRDDVVPRTIRDHAKLVDVGINFRRLEFVNSDVEGLEGGDLS TVTESLAMLPEVYEEPSPSALEGKDISPLLRESESEGEGELSPPGAVAQLFPLPSSPILASG GEPSPEGTPWKVPDKNTSCPCCGTRIGKVSGLVEHLRRVHGRRKILFQCALCGKTNEKHHS IACHVPKCKGAIEATPKEGLACEECGRTFETKIGLGQHKRLAHPVTRNLERIMAARPKETSA RGVHRKCWTEEEVEILRKLEKQYEGNRNINKLIAEELPFKTAKQISDKRRILHKSPVKKREE DQEWKKHLREGEHLVSIGPRKRGGGLKSHYRKTISKWITAGKLRILHATFEKVIEGGEDLPT TVGGAVEDCYARLFKRSSELEASQGRKLQTARTARSSEPPKEWMKKRARKRGEFLRFQRLFH LDRGKLAGIILDDVESLKCGLPLDEVHCVFKSRWESPGTFKGLGGFKTLGRADNSAFEAMIT SKEISKNIKEMSKNSAPGPDGLSLRGLMAIDPHYTMLAELYNLWLLTGTIPDMVKECRTVLI SKSALPERQKDINNWRPITIGSTVLRLFSRIITARLTKACPISPRQRGFIRSAGCAENLKLL QLLIRNAKREKHPLGWFVDLAKAFDTVSHNHIIEVLKQKGVDNHIISLISNMYSNTHTYID MKSEQSDPIGIRIGVKQGDPMSPILFNLSVDPLLCVLEKEGSGYQHYSTSITSMAFADDLVL LSGSWEGMRRNIEIVEAFCDLTGLKTQGEKCHGFYIQPTKDSYTINDCPAWTIKGTPENMIE PGSSEKYLGLKIDPWVGISKPELLAKIKDWLHRIDRAPLKPMQKVDILKVYTIPRMIYLADQ SDVKVSYLESLDLTIRTAVKEWVHLPPSTCDAILYSSTRDGGLGLTRLSGLIPSVQARRLHR IAQSSDEVIREIVSKEGIEKEYEKLWLAAGGNKEKIPSIWDPSSAMVITEVLGGIDQYSEWE RPAPKTIFPKPSDWRKQEFIKWTKLASQGRGITNFEKDKISNSWLERYRGIPQRKIVTALQL RAWYPTREFLARGRQETHVRSCRHCGAEIESCSHIIGYCPAVQDARIKRHNQICELLIEEA KKKEWIAFQEPLIRDEKKELFKPDLVFVREEIAIVVDVTIRYESKETSLEDAAKEKIKKYQH LEDQIQELTNATTIKFMGFPLGARGKWYQGNYTLLKELGLSSSRQDKVARRLSNRALFSSVD IIHMFS S KVRTVENV 173 (44) R2TyAI RT ECRTVLISKSALPERQKDINNWRPITIGSTVLRLFSRIITARLTKACPISPRQRGFIRSAGC AENLKLLQLLIRNAKREKHPLGVVFVDLAKAFDTVSHNHIIEVLKQKGVDNHIISLISNMYS NTHTYIDMKSEQSDPIGIRIGVKQGDPMSPILFNLSVDPLLCVLEKEGSGYQHYSTSITSMA FADDLVLLSGSWEGMRRNIEIVEAFCDLTGLKTQGEKCHGFYIQPTKDSYTINDCPAWTIKG TPLNMIEPGSSEKYLGLKI 174 (44) R2TyAI 5'UTR ACGGGATCATAGTTACTAACTGGGCTCAGCTGCAGAGGTCACGCCTCCTCGTGGTCCCGCCG GATACCCTCTTGGGTAACTGAAGTGGCCTCTGCCCCAGTGTGATGAGATATGGTTACTTCCT C C C TAT C AAGT GAC T T C AC C GAC C ACT T GAT AGT AT C T AAT T GGT GAT AC AAAAT T T C GGAG TCTTAATTGACTACCCAGAGCCTGGCCCACGGGCCTATGTTGGGCGCAGTCTGACAGCTCGT AAGGGAGTGCTGTCTGGCTTAAATTTGACCCTTACCTGGATTTGACAAA 175 (44) R2TyAI 3'UTR TTGTATCATCACATTGTAGTTGTAATATCTGTGCACTGTATTACTTTTAATTAATAAAATAA AGTGGTATGAAGAGCCGACATGGAAGGATCGTGGGGGGGTTAGATCAGGAGAGAAAACGATC AGAGTATTGGGATTTCAACATAGTAGGTGGGAATCTTGTTCTTTTTATGACGCGTCTCAACC GAAATTGACATTAACAATTGGACTTGACAAAATTTTTCACCAATTTGGACCCAGGTGGACGG GCCACCTTTACTTAACT CGGAAAAGAAAC AT AT AT AAT TTATATGTGTTT GAT AAA 176 (45) R2ViLa ORF MFPCIDDPRPPGPPDRSSPGRRSRVACRESDAKDPGHVCPCGSEFQSKQGLAMHRYHRHMAE ENAKRLASLPSKRLAWSQEEDRALLRLATAQWTGGMAKVTLFGLLQPQFPGRSVEAIKKRLQ GLKWTAPADNPERDPLPVPPSTAQGDVEPATSPAPTADPRVFDQNTDDPTVSWRRALLTAVE GKLSEPKMGADTLCRIASQLKNGEINGEACRALMNEHAREWFPHTWKPSSVKDQTDTRRWSK RAIRRANYATVQRLFKLRRRDAAHTVLSGRWRNAYRGQAPLPKGMDQYWSKVFEAGSAKDEK AQVVPDKTLWETLAAVTPSEVTSALKGMKASAPGLDRISAEDLLAWNQPSLAAYFNLMLAAG GPPEQLACSRVTFIPKVDEPKTPGDYRPISIASVILRAFHKILAWRLRDTVQLSPFQHGFLQ RDGCLEASALLHTILRKSHRDRKPCALLFLDVAKAFDTVSHQTLFRVATAMGLPPPLVDYLK HLYGRSTVQIAGQNTKCGRGVRQGDPLSPLLFIMVMEDIVRDALPEVGFDLDGQRVDSLAYA DDLVLLAEKSSRLQEKLTLLTAALQNAGMELNARKSHGLTIEKASKRKCMVLRDTKYQCKGE GIQPMGTDDSVRYLGLHFNWKGRLVPKHTGKLDSLLKELSAAPLKPFQRLQLLKLHVVPKFV HELVLGHAHRNTLQKLDCLIRAAVRQWLRLPTDTPLGYLHANIKDGGLGIPCFSTSIPLLQQ KRFEKIAQNPATIFQIIQRQDSFRTLGRRLDRPCRLQGAVLTSKAEAREEWGNVLSNSVDGR ELRYPDVDKASHEWLLRPSRVFPRLHMRGIQLRGGLLPTKARSARGNNRQVQDKTCRGACRQ PETLNHILQVCEVTHDGRCARHNRVLHRLAQLLRKKGVRTTLEPVIPSGSSFIKPDLIAETD KQTYVLDVSWAGGRMKTSWDIKDEKYGRPDRVNDIRKWGAIPEASRVCQLPIIISNRGLCY QATGEGLRALGLTTREISDLCLLAISGSLKCYDLYMRGTRGVRGAPEHRYGAPKGPH 177 (45) R2ViLa RT CSRVTFIPKVDEPKTPGDYRPISIASVILRAFHKILAWRLRDTVQLSPFQHGFLQRDGCLEA SALLHTILRKSHRDRKPCALLFLDVAKAFDTVSHQTLFRVATAMGLPPPLVDYLKHLYGRST VQIAGQNTKCGRGVRQGDPLSPLLFIMVMEDIVRDALPEVGFDLDGQRVDSLAYADDLVLLA EKSSRLQEKLTLLTAALQNAGMELNARKSHGLTIEKASKRKCMVLRDTKYQCKGEGIQPMGT DDSVRYLGLHF 178 (45) R2ViLa 5'UTR CTCCCGTCGCTTGACATTGGCGTTTTTTCGCAGTGCGTATATCAATTGCGAGAGCTAGTCTT TGTCCTTGGCGTGAGTTGATTGCATAGTTGCACGGGTTAGACACCTCCTAGTGGTGACCGCT GGATAAGGCCTCCGGGCCCGAACCAAGATCTAACCCACCCTCCGTTGCAGAAACAGCGGAGG CTAAACTGCTGCTA 179 (45) R2ViLa 3'UTR GTGGTGACCCCTCTGGTCGACACCTGGACTAGCGACCAAGTCGCCTTAGAAGACCTGATGGG GGGGGTCTCCGTACCCTTTCTCGTCTTGTCTCTCTAATAATACATGTGAAAA 180 (46) R2Tral ORF MLTLHMDPRPPGSPDPSWPGSCPREVCQESAAEPPKHSCPCGSEFRTKRGLAMHRSHRHQAE VNAERLASLPTRKLVWTQEEEAGLLRHATQAWKKGMAKTQIFASLLPHFPGRSVEAIKKRLQ SLKWVPPRDTPERNSQPLNATSGNVAPATLPAPDSSVTIDDQGRVEDPAASWRRALLTAAAV RLSEPKLGAETLRQITQDLQDGKISSKKCRVLMNEHAQHWFPHKWKPTSVRPEPKTRQWSTR EIRRANYASVQKLYKLRKRDAAQTVFSGRWRNAYRGQAPLPAEMDEYWAKIFETPSAIDSVT PEVPSKVLWSVMGKIVPSEVTDALKGMRNSAPGLDRISAEELLTWHQPSLAAYYNLMLAAGG PPEHLACSRVTFIPKLENPQAPGDYRPISIASTILRALHKILAWRLRDTLQLSPFQHGFLQR DGCLEASALLHAILRKVHNSRKSCAMLFLDVAKAFDTVSHQTLFRVASAMGLPPPLVHYLKH L Y SRS TVRLANKVTTCGRGVRQGDPLS PLLFIMVMEDIVRE AL PE VGFNLDGQRVD S LAYAD DLVLLAEKSPRLQEKLHRLAEALRKAGMSLNARKSHGLTVTKVSKRKQMVLSPTSYECEGET IKPMGTDDSVRYLGLHFNWKGRIVPKHTGLWDSLLKELKKAPLKPYQRLQLLRFHAVPKFTH QLVLGHAHRNTLKKLDCLTRAAVRQWLRLPPDTPLGYLHANVKDGGLGIPCFSTSIPLLQQK RFEKIATNPATIFQVIERQDSFRTQRRRLDRPCRLNKTVVTSKAEVREGWGNMLSNSVDGKE LRYPEVDKASHEWLLRPSRVFPRLHLRGIQLRGGLLPTKARSGRGKNRQVTNKTCRGACQNV ETLNHILQVCEVTHDARCARHNRVLHLLEKLIRKKGARATLEPVIPAGSSFIKPDLIIETDT QMFVLDVSVVAGYRMAESWDIKVEKYGRPDRVEAIRRWAAIPEKIRVEQLPVIVSNRGLCYR PSGVGLRALGLTSRDISDLCLLAISGSLRCYDLYMRGTRASKEN 181 (46) R2Tral RT CSRVTFIPKLENPQAPGDYRPISIASTILRALHKILAWRLRDTLQLSPFQHGFLQRDGCLEA SALLHAILRKVHNSRKSCAMLFLDVAKAFDTVSHQTLFRVASAMGLPPPLVHYLKHLYSRST VRLANKVTTCGRGVRQGDPLSPLLFIMVMEDIVREALPEVGFNLDGQRVDSLAYADDLVLLA EKSPRLQEKLHRLAEALRKAGMSLNARKSHGLTVTKVSKRKQMVLSPTSYECEGETIKPMGT DDSVRYLGLHF 182 (46) R2Tral 5'UTR TACCCATTGGTCTTGATTTTGATACTGGTGTTTTGCGAATTGGTGTTGATTGCAAAGTGTTG TTGCGGTGAATTGACGATTGGTTGCTAGGGTTGGGCACCTCCAAGTGGTACCCGCTGGATAG GGCCTTCGTGCCTGAACTAAGCCCCAACCCACCTCTCCGTTGCTGGCAGACCACAGTAACTG AGATTAAACAGCTGGT 183 (46) R2Tral 3'UTR GCAGTGCCGAACGGGACCCAGAGGACCGCCTCGCCGATCAGGCGTGGGCGGTGACCACCCTG GCCTCTACCTGAAATAGCGATCTAATCGCCTTAGAAGGCTTGATGCTGGAGGGTCGAGCAGA CACCAAGTGTCACGAATGCTCCTTACCCTACCTCTTCTTGCTTCTCTAATAATCAATGTTAA CA 184 (47) R2Boja ORF MLTRTDDPRPPGHPDPSCPGSCSRDCRESVAESPRHACPCGCEFPTKRGLAMHRFHRHMAEV NAERLATLPTKKLAWTQEEEAGLLRHASQAWKEGMTKTQIFAAVLPHFPGRSMEAIKKRLQS LKWVPPQNTPERNLQPLHATSGNVAPAALPSPDSSVKVDGQGQNTEDPAASWRRALLAAAVD HLEEPKLGAETLRQITQDLENGKISSKKCRVLMNEHAKHWFPHTWKPSSARPEPKARQWSNR EIRRGNYGAIQKLYKLRKRDAAQTVLSGRWRTAYRGRAPMPAKMEEYWSEVFQAPSATDAIP PGSPSDTLWSVMGKITSSEVTAALKGMRNSAPGLDRITAEELLTWHQPSLASYYNLMLVAGG PPKHLACSRVTFIQKVELPQTPGDYRPISIASTILRALHKILAWRLRDTLRLSPFQHGFLQR DGCLEATALLHAILRKVHNSRKPCAMLFLDVAKAFDTVSHQTLFRVASEMGLPPPLVNYLKY LYSRSTIKLADKVIKCGRGVRQGDPLSPLLFIMVMEVIVREALPEVGFNLDGQRVDSLAYAD DLVLLAEKSTRLQEKLERLSEALRKAGMALNARKSHGLTVTKASKRKQMVLTPTTYECEGDT IRPMGTDDSVRYLGLHFNWKGRIVPKHTGKLDTLLKELTRAPLKPYQRLELLRFHTVPKLTH ELVLGHAHRNTLKKLDCLTRAAVRQWLRLPQDTPLGYLHAHVKDGGLGIPCFSTSIPLLQQR RFEKIATNPATIFQVLQRQDSFRTQWRRLDKPCRLNSTVVTSKVEVRKEWENMLSNSVDGRE LRYPEVDKASHEWLLRPSRVFPRLHMRGIQLRGGLLPTKARSGRGKNRQVTSKTCRGACQTV ETLNHILQVCEVTHDARCARHNRVLHHLEKLLRKKGIRTTLEPVIPAGSSFIKPDLIIETDT KLFVLDVSVVAGYRMAESWSIKVEKYGRPDRVEAIRRWAAIPEEIRVEHLPVIVSNRGLCYR PSGDGLRALGLTSRDISDLCLLAINGSLRCYDLYMRGTRATRETERHLP 185 (47) R2Boja RT CSRVTFIQKVELPQTPGDYRPISIASTILRALHKILAWRLRDTLRLSPFQHGFLQRDGCLEA TALLHAILRKVHNSRKPCAMLFLDVAKAFDTVSHQTLFRVASEMGLPPPLVNYLKYLYSRST IKLADKVIKCGRGVRQGDPLSPLLFIMVMEVIVREALPEVGFNLDGQRVDSLAYADDLVLLA EKSTRLQEKLERLSEALRKAGMALNARKSHGLTVTKASKRKQMVLTPTTYECEGDTIRPMGT 186 DDSVRYLGLHF (47) R2Boja 5'UTR CCACTTGGTGTTGATTTGGATTTTGGTACTGGCGACTTGCTAGTTGGTATTGATTGCAAAGT GTTGTTGCAGGTTGAGCGGACGATTGGTTGCGCGGGTTGGACACCTCCACGTGGTGACCGCT GGATAAGGCTACGGGCCTTAACTAAGATCCAACCCACCCCTCCGTTACTGACAGACCACAGT AAC TGAGAT TAAACAGC TGGC 187 (47) R2Boja 3'UTR CAAAGAGGACCCCTCTCTGATTAGGCGGTGACCACCCTGGCCTCTACCGAAATAGCGATCAA ATCGCCTTAGAGGGCTTGATTTGGGAGGCTGAGCTGACACTGTGTGTCGCGAACGCTCTTTG CCTTTCCTCTTCTTGCCTATCTAATAACCCGTGTTAATA 188 (48) R2Bofu ORF MDRNTNVKGPHASSPSNAFTCSCGRQFSTKRGLGMHRRHCQPVEVNIERMAVLPTKRLIWSL EEDEALRRCADHQWKTGMLKKDLYTLLLPHFPGRSQEAIKKRLQTIKWVPPTDPALVSHPPP GVDTGSASDRGRDSSAASDSDPDPAATWSSLLTATTSNLQEAKMGAEELYVIARDLAMGVI SQTQSRALLQDHAQKWFPHLWKPSKPRPLSRTHQWSKRTVRRANYAVIQRLYKLRRRDAAST IFSGQWKNAYRGSPPLPPDMESYWSSVFQTPSAIDDRVPATPSEVYWTLLCAMTPSEVTAAL KSMASSAPGLDRITAATLLTWHQPSIAAYFNLLLAAGGPPEHLACSRWFLPKTEAPSTPGE FRPISIASTILRAFHKILSWRLRDTLQLSPFQHGFLQQDGCLEATTLLHTILRRVHLKCEPC AMLFWIAKAFDTVSHHTLFRVATAAGLPPPLVCYLRHLYERSTIQLAGTTTVCGRGVRQGD PLSPLLFILVIEDIVTSSLPSIGYDWGHRIHSIAYADDLVLFAEKSPRLQEKLHLLSEALS KAGMTLNAKKSIGLTIAKDGKRKRTALLPTTYRCGIGNINPLGPGETLRYLGIQFNWKGRVT PKHTGKLETLLQELTQAPLKPQQRLLLLKFFLVPKFTHELVLGHAHRNTLRKMDWLIRAAVR RWLRLPKDTPVGYLHAHIKDGGLGVPCLSTTIPLLQASRLEKIAAHPTTLFQQIQRQDALGP LRRRMNQPCRINTTTVTTKAEAREEWKSTLVASFDGRELGVPKVDPVSHDWLLRPSRVFPRL FLRGIQLRGGVLPTKSRSARGANRKWDKICRGACRATETINHTLQVCEVTHDARCARHNRI VRRLDQLLRRQGIQPSVEPIIPSGTSFTKPDLIAETNNRLWVMDVSVVAGHRMQETWKIKVD KYGKPEQVASILRWAAVDSSVPVHHLPIVITNRGLIFEPSAAGLRTLGLSRRDLVDLCLLTI MGS LKCYDVYMRGTF 189 (48) R2Bofu RT CSRWFLPKTEAPSTPGEFRPISIASTILRAFHKILSWRLRDTLQLSPFQHGFLQQDGCLEA TTLLHTILRRVHLKCEPCAMLFLDIAKAFDTVSHHTLFRVATAAGLPPPLVCYLRHLYERST IQLAGTTTVCGRGVRQGDPLSPLLFILVIEDIVTSSLPSIGYDLDGHRIHSIAYADDLVLFA EKSPRLQEKLHLLSEALSKAGMTLNAKKSIGLTIAKDGKRKRTALLPTTYRCGIGNINPLGP GETLRYLGIQF 190 (48) R2Bofu 5'UTR TGGTTACGCGGCCTGGACGCCTCCTAGTGGCGACCGCTGGATAAGGGGTAGATAGTTTAACT TCTGCTCCCGAGCTAAGAGCCAGGCCACCCCTCGGCGAGGTTAGTACCTTGTTGAGGTTTCA CTGCTGGTTTTCTAATTGAAAGGAATTGTCCCGGTCCCCCTGGACTTAAGGACTCCAGCAGC 191 (48) R2Bofu 3'UTR GGTTGAACTGGCTTCTATTGGTCCCCCCCCCAACACATTAGTGTACTACTCAATTAGCGACT TGTCGCTCTCAGGGAGGCTCTCCTCCCTGATAATATATGTCACG 192 (49) R2CroTig ORF MLTDTWLRPPGLPDPSCPGSCPRVASPKSDAECPKHSCPCGSEFRTKRGLAMHRFHCHPAE VNAERLTTLPTKKLVWTQEEMDGLLRHANGAWKEGMLKTQIFTSLMPHFPGRSAEAIKKRLQ SLKWVPARDNPERNSQPLHATSGNVAPATLPTPDPSRVDDQGANIEDPAASWRRALLTAAAD HFKEPKLGAGTLKQITQDLLNGKISSRECRVLMGEHAQHWFPHTWKPSSARPEPKARQWKAR EIRRANYAAVQKLYKLRRRDAAQAVFSGSWRNAYRGRAPQPDKMDQYWAEVFETASATDVTP PGSPSEIYWSVVSKITPSEVADALKGMRNSAPGLDRITAEELLTWDHPSLAAYYNLMLAAGG PPEHLACSRVTFIPKVENPQTPGDYRPISVASTVLRAFHKILAWRLRDNLQLSPFQHGFLQR DGCLEATALLHTILRKVHNSRKSCAMLFLDVAKAFDTVSHQTLFRVAVELGLPPPLVNYLKC LYSRSTVRLADKATKCGRGVRQGDPLSPLLFIMVMDDIVRKTLPEVGFDLDGQRVDSLAYAD DLVLLAEKSPRLQDKLHLLSEALRKAGMSIJSIARKSRGLTITKVSKRKQMVITPTTYECEGEP IKPMGTDDSVRYLGLHFNWKGRIVPKHTGKLDSLLKELTKAPLKPYQRLQLLKFHAVPKFTH ELVLGHAHRNTVKKLDCLTRAAVRKWLRLPQDTPLGYLHANVKDGGLGIPCFSTSIPLLQKK RFEKIATNPATIFQIMQRQDSFRTQGRRLDKPCRLNSTWTSKTEVREEWGNMLSNSVDGRE LRHPEVDKASHEWLLRPDRVFPRLHMRGIQLRGGLLPTKARSGRGNNRQVTSKTCRGACQNV ETLNHILQVCDVTHDARCARHNRVLHRLERLLHKKGLRTTLEPVIPAGSSFIKPDLIIETDT QTYVLDVSVVAGYRMTESWDIKVEKYGRPDRVEAIRKWAAIPATKRVEHLPVIVSNRGLCYQ PSGDGLRALGLTSRDISDLCLLAISGSLRCYDLYMRGTRAV 193 (49) R2CroTig RT CSRVTFIPKVENPQTPGDYRPISVASTVLRAFHKILAWRLRDNLQLSPFQHGFLQRDGCLEA TALLHTILRKVHNSRKSCAMLFLDVAKAFDTVSHQTLFRVAVELGLPPPLVNYLKCLYSRST VRLADKATKCGRGVRQGDPLSPLLFIMVMDDIVRKTLPEVGFDLDGQRVDSLAYADDLVLLA EKSPRLQDKLHLLSEALRKAGMSLNARKSRGLTITKVSKRKQMVITPTTYECEGEPIKPMGT DDSVRYLGLHF 194 (49) R2CroTig 5'UTR TCGACCATTTGGTGTTGATATTGATACTGGCGACTGGCTAGTTGGTGTTGGTTGAAAGTGCT GGCGAGGTTGAGCTGATAATTGGTTGCACGGGTTGGGCACCTCCTAGTGGTGACCGCTGGAT AGGGCTTCGGCCTGAGCCAAGATCCAACCCACCCTCCGTTGCTGGCAGACCCCAGTAACTGA GAT TAAACAGCTGGT 195 (49) R2CroTig 3'UTR GACTACCGAGCGCCACCGGAGGGGACCCAGAGGACCGTCTCGGTGATTAGGCGGTGACCGCC CTGGCCTCTACCTGAAATAGCGATCAAATCGCCTTAGAGGGCCTGATTTGGGGGGTTGGGCA GACACTCTGTGTCATTACTGCCCTTTACCTTTCCACTTCTTGCCTGTCTAATAATAAATGTT AACA 196 (50) R2GraSmi ORF MTIITNPSPPGPSDPSDTDRYPGHTDTRDSPRERQEDRKETQQYICHCGSRFKSIRGLGRHR AHRHMAEVNAERVAALPTKRLKWSQEDDEALCRLASRHWVLGMTKKTLIAQITSFFPGRSHE ALKKRLNSVNWGPPNVTPERTNIPQPEHPERLANLIGPVAHTASEPGHPDRPTKVATPDGPV AHSHPEPDQDAATSWRCALLGAAADRLKEVKLGAGELAQIARDLQNGCTRKQCRARLNHHAK KWFPHTWKPSVPRAQDANRQWSKTAIRRANYAQVQKLYKLRQRDAASTVLSGSWRTAYKGPA PVPPKMEEYWAAVFNTPSVVDTSVPAEPPAVLWSLMAAITPSEVTAALTGMKASAPGLDRLS ALELLSWDQPSLAAYYNLLLAAGGPPKHLTCSRWFLPKTENPSAPGDYRPISLASTILRAF HKIMAWRLRBTLQFSPLQHAFLQRDGCLEASTLLHNILRRIHTDRVQGAMLFLDVAKAFDTV SHSSLFRVAYEAGLPPPLVSYLRHLYRHSTVRLAETTTKCGRGVRQGDPLSPLLFIMVIDDV VKNSLPDVGFDFDGHRVGSLAYADDLILFAEKHTRLQEKLHLLSEALQRAGMALNTKKSHGL TIAKDGKRKCMALVPTPYECKGATILPLGTDDTVRYLGLQFNWKGRVIPKHTGRLDTLLDEL TRAPLKPHQRLKLLRVYTCPKLTHELVLGHAHRNTLKKLDCLTRAAVRRWLRLPTDTPTGYF HAHVSDGGLGLPCFSTTIPLLQQKRLEKVACNPATLFQILQRQSSFRSLERRLDQPCRLNGA VVTSKAEVREGWQIMLSDSIDGRELSIPGVDKASYEWLRHPARVFPRLYIRGIQLRCGLLPT KARSARGANRQVIARTCKGACCASETQNHILQVCELTHDVRCARHNRILRYLNKQLHRLGLQ TWVEPVIPSGSSFIKPDLIVETEKQLWVLDVSIVAGYRLEESWNIKAAKYGRSDRWDIRRW ATVPDSTFVCQLPVIISNRGLLYAPSGVGLRALGLSRRDIMDLCLLAISGSLKCYDLYMRGN 197 (50) R2GraSmi RT CSRWFLPKTENPSAPGDYRPISIASTILRAFHKIMAWRLRDTLQFSPLQHAFLQRDGCLEA STLLHNILRRIHTDRVQGAMLFLDVAKAFDTVSHSSLFRVAYEAGLPPPLVSYLRHLYRHST VRLAETTTKCGRGVRQGDPLSPLLFIMVIDDWKNSLPDVGFDFDGHRVGSLAYADDLILFA EKHTRLQEKLHLLSEALQRAGMALNTKKSHGLTIAKDGKRKCMALVPTPYECKGATILPLGT DDTVRYLGLQF 198 (50) R2GraSmi 5'UTR TTAAGAAATCGTTCATAGTTACAGGCTTGGGCGCCTCCGTGTGGCGACCGCTGGATAGGGCA CATTGTGCCTGAGCTAAGACCCAAGCCACCCCTCTCCTGGTCTAATTGCTTTGGAGAGGGAC T GT C AC T GGT T C AAT AC AT AT T 199 (50) R2GraSmi 3'UTR GCTTGGACTGGATTGTTTTCTTATCTGTATATATGTATATATTATTATGATGTCTGTATTGT GACGTACCATGTGGTCTCTATCTCATAGCGAGTGATTCGCCCTAGAAAGCTTGGTGGGCGGG ACGGGAATTGTCAGGTTGCTTTTTATATCGTACCATTGGGTTATCGTGCACTGCTTTCCTAT GCCTGTACTGCCTTGCTATTCTAAAATAAACAGTTAAC 200 (51) R2SibCol ORF MTIVFSPSPPGHPDPSDIDGNANSTGSQNGGDKPSFPCFCGSRFKTKRGLGQHRSRCHPAEV NAERIAALPTRRLTWTHEDDEALRRHADQHWEKGMMKKVLITKLTPYFPGRSHEAIKKRLQL LKWDPLKENPERILYPQTHDCPERPHTDAPPTSPVAAQLTHELDPSAATTWRSALLTAAADH LKENKMGANELTQIARDLQAGVASRKQCRARLNQHAQSWFPHTWKPSVARPKTATHQWSKKA IRRANYATIQKLYRLRRRDAASTVLSGRWRNAYKGPTPVPPEMEEYWSTVFKTPSATDDRKP AEPSAVLWS LMVAIAPSEVSAALQGMKASAPGPDRIPAVELLTWDQPSLAAYYNLLLAVGGP PKHLSCSRWFLPKTEDPMTPGDFRPISIASTILRAFHKILARRLRDTLQLSPLQHAFLQRD GCLEATTLLHTIIRRIHEDRVPCAMLFWIAKVFDTVSHQSLFRVAYEAGLPRPLVSYLRHL YKKSTVRLAEATTKCGRGVRQGDHLSPLLFIMVIEDIIKTALPDIGFDLNGQTIGSLAYADD LVLLAGKSSRLQEKLHLLSGALQQAGMALNAKKSHGLTIAKDGKRKCMSLVPTLYECKGDNI QPLGTDDSVRYLGLQFNWKGRVIPKHTGKLDNLLNELTKAPLKPHQRLKLLKSHLVPKFTHE LVLGHAHRNTLKRLDWLMRVAVRHWLRLPTDTPLGYFHANVLDGGLGLPFFSTSIPLLQQKR LEKVALNPATLFQIVQRQNSFRSLGRRMDQPCRLNGTWTSKKEVREEWQNMLSNSVDGKEL SIPEVYKASHEWLRRPDRVFPRLYIRGIQLRGGLLPTKARSARGNNRQVTDRTCRGSCCAPE TLNHILQVCKVTHDARCTRHNRVLGYLEKLLRRAEIRTRVEPVIPSGSSFIKPDLIVETANQ LWVLDVSIVAGYRMEDTWDIKAAKYGRPDHVADIRRWAAVPATTPVTQLPVIVSNRGLFHQP SGDGLRALGLSRRDIMDMCIYAIRGSLKCYDLYMRGTSGWKNV 201 (51) R2SibCol RT CSRWFLPKTEDPMTPGDFRPISIASTILRAFHKILARRLRDTLQLSPLQHAFLQRDGCLEA TTLLHTIIRRIHEDRVPCAMLFLDIAKVFDTVSHQSLFRVAYEAGLPRPLVSYLRHLYKKST VRLAEATTKCGRGVRQGDHLSPLLFIMVIEDIIKTALPDIGFDLNGQTIGSLAYADDLVLLA GKSSRLQEKLHLLSGALQQAGMALNAKKSHGLTIAKDGKRKCMSLVPTLYECKGDNIQPLGT DDSVRYLGLQF 202 (51) R2SibCol 5'UTR TTAAACAGCGTATAGTTGCAGGGCTTGGACGCCTCCCCGTGGCGACCGCTGGATATGGTACC CTAAGTGCCAGAACTAAGATCCAAGCCCCCCCTCTGCGAGGGCCCAAGTCTCGTAGAGGATT CGTTGCTGGTTATTAAA 203 (51) R2SibCol 3'UTR TCTGTTTTGAAGGGCCTGTAACCTATTGACATTACTGTCTGATAGCAGTTTTATCTGCCTTA GAGGGCCTGGCGGGCGGGTTGGTATAGTGAGATGTGTGTACTGTATTGTACTGTATTGCCTA ATATTGTATCGTACTGTATTGTGCATTGCCTTACCTTGTACCGTACTGACTTGCTTTTCTAA AAAT AAAAT GT GAC T 204 (52) R2LacBil ORF MNHRGNAKRGGGSTDRTTGVRSSSRAAGPGVVPAVEPPVFVCEYPGCERTFNTKTGRGVHHR RAHQDWYDAQQNIHQVKRRWTPEETSLLAREEARLLTSGTRHMNLALMEKFPERTAEAIKAH RRQQAYRELWAYTQEQLEVAARPAPQPVVEASNTQWRNRLIQHLQRLPRMTATTEHLERLY RLSATVELRSLTDVFDELSLVLRGMQGTRPWRAQRGERSSQETPTSNRRKRRKQFAKFQHLW HKSPTKCIKWALDKNRDAPIENGADLFPFWEKLMTRAPDCTPGPGPRRNEITSLWEPITAAE IKRALPSASTAPGPDGMTVEQVKRLPLGVLERLFNLIMVCGKCPQSMLGARTTLIPKKEYAR DPGDFRPITVSPVLTRVFHKVLAAQLTREVDLDPRQRAFQQFDGCSENIFLLDMVLRYHKQR FKPLYIASLDVAKAFD S VAH Y TI KE TLQMMGVPDPMTH YISDVYDRS TTVL SCGGAT SQEFH PRCGVKQGDPMSPCIFNMIMDRLLRKIPREVGADLGEGVTENGVAFADDLVLLASTPVGLQT PIDIVADHLALCGLTVNSGKSLTVSLETVPREKKTWNPRRVFTCNNRPLQALKRSDQWRYL GVPFTPDGRMSARPLDRLRELLDTIGKAPLKPQQRMFGLRTVLLPSLYHQLSMGSTTVGLLN KVDRCVRTAVRKWLGLPDSTPVAYFHAKVGDGGLGIPAMRWMMPRLRRDQLLRLPLQRTEES TSGTFLRRELSLVEGRLLERGNSLFTSQAQDRRWASLLYQSVDGCALRESGKTRSQHDWVYG CTRFLSGKDYRNSIRMRINALPTRSRLARGRRADRLCRGGCQMPETLNHVLQVCYRSHAARV RRHDAWKYISKGLRRQGYHVDLEPHFRTSEGLRKPDIVAS IGRTARIIDAQVVGEQADLRR AHAQKVQYYAGNSSLLEMVKQRYQVDDLCTTSATLSCRGVWSDRSAEDLLAMGIVRKQDLKV LSSRVVLGGIYAHSVFNKTTASLSAGW 205 (52) R2LacBil RT GARTTLIPKKEYARDPGDFRPITVSPVLTRVFHKVLAAQLTREVDLDPRQRAFQQFDGCSEN IFLLDMVLRYHKQRFKPLYIASLDVAKAFDSVAHYTIKETLQMMGVPDPMTHYISDVYDRST TVLSCGGATSQEFHPRCGVKQGDPMSPCIFNMIMDRLLRKIPREVGADLGEGVTENGVAFAD DLVLLASTPVGLQTPTDTVADHLALCGLTVNSGKSLTVSLETVPREKKTWNPRRVFTCNNR P L QAL KR S D QWRYL GVP F 206 (52) R2LacBil 5'UTR GGGAATGACTGCTGATGATCTGTGATGTTAATCTGACGATCTTCGGAGGTCTTTTCCACGTG CCTATCCCTACCTCCTCGTGGTGAGAGTCGGGCAACGTCTTTAGGCATACGTCTTTAGGCGG CTAACAGGGAAGGCTTACCTGAGGCTCTGGGTCCTATACCAGAGAGTCTCAGTTCAACCTCA CCCAGATTCGGGCATCCCCCGAA 207 (52) R2LacBil 3'UTR GCGCCCAGGAAATTGCCCAGGTGTAGCACGGGACTGCTAGAAAAATAGTCCGTACGTCTGCG GATATACAGACGCAATTTCTGAGGGGCGTGGCGCCCCGATGATGACGGAAA 208 (53) R2LiaOli ORF MEAAEFRCACGRVWPSARSLAMHNHHRHPEVVNEARLQARPVSRLHWTGEEEEALRRLADRT WTAGMLKGELCSKLADSFPGRSAEAIKKRLQHIKWAPLSSGAISSEASTPRAALICDGFDPV EWRKKLLGDTVKNLNEPRMGSDTLVATSQRLRTGELSLVAAVECLEDHAKQWFPHKWRPSTP RSQKPTQPHSRKAIRRATYAAVQRLYYRRQKDAASAVLSGQWRDIYRQRKEWGLNRHWAKV FEIPSVADTEPPIMPSNLLCSLLDRIHPSEVTAALGDMTASAPGLDRLTAGELLKWHQPSLS AYFNLLLAVEAPPRHLACSRTAFIPKVADPTSPEEFRPISIASVLLRAFHKILARRLRDHLD LSSLQFAFLLRDGCLEATTLLRSVLRRIHHERTSCAMLFLDISKAFDTVSHGTLSRVMRSAG FPPPLVSYIQHLYECSTVQLGDTMVSCNRGVRQGDPLSPLLFILVIDDILRKSLPEVGYNFG GLRLGAMAYADDIVLLADHPQRLQEKLDVFSQALHAAGMALNAKKSVGLTWRDGKRKWAL DPTCYNYRDGPIRSVGLRESVRYLGLQFDWKGQVRFKHTRKIDSMLEEITRAPLKPHQRLRI LSAFLIPKFTHELVLGAAHRKTLLQLDRQVRVAVRSWLHLPKDTPLGFFHASVRDGGIGIPS FSTTIPILQKNRFEKLASQTSQWSVWRDQAAFRVLSNIVNRPCKLNNMAVTTKKESRVEWQ RALSQSVDGNEVAIPGVDPVSHRWLRDPSRVFPRLFLRGIQLRGGVLPTRARSARGINREVT DKRCRGPCQASETINHILQACEITHDARCARHNRVLQRLDQCIRKGGAETWVEPIICSGSSF IKPDLIVSKLDHLWTLDVSWAAPRLPVTWDLKVAKYGSAVCARDISTWHASSVPLKHLPVV FSNRGLCYEPSGKGLRALGLSHRDIMDLCLLTIQGSLKCYDLYTRGTRSGFGGTV 209 (53) R2LiaOli RT CSRTAFIPKVADPTSPEEFRPISIASVLLRAFHKILARRLRDHLDLSSLQFAFLLRDGCLEA TTLLRSVLRRIHHERTSCAMLFLDISKAFDTVSHGTLSRVMRSAGFPPPLVSYIQHLYECST VQLGDTMVSCNRGVRQGDPLSPLLFILVIDDILRKSLPEVGYNFGGLRLGAMAYADDIVLLA DHPQRLQEKLDVFSQALHAAGMALNAKKSVGLTWRDGKRKWALDPTCYNYRDGPIRSVGL RESVRYLGLQF 210 (53) R2LiaOli 5'UTR AGGGCATAGTTGCACGGCCTGGGCGCCTCCACGTGGCGACCGCTGGATAGGGTGCATTTTTA CACCTGAACTAAGATCCAGGCCACCCTCCTTTTGGGCTTGATTTCCCAATAGGAGGTTCTCT GCTGGTTTCCGAACCAATTTGTAATTGTTGTCCTGTGCTCTCTGGTGGCAGGACTTCCAGCA GACATAGTGCCAGTAACTTCCTTGGCCAATTAGCAGTCCACC 211 (53) R2LiaOIi 3'UTR AGTTTAGTGGGGTGGGTGTGAGATCTGGGTCAAGGAATGTTCCTTTAGAACGGCGCTAGTTA ATTAGCGAGTTTTCGCCTTGGAGGATGATTATGCTTGGTTAACGTCCCCCAAGATATTGGTG GGT T C GGAAC C T GT T T GAT TAT C T GT AC C AAT AAT AAT AAAT GAT AAAA 212 (54) R2MasLat ORF MDPSNKDGNASSVGTQDNNTRPSYRCFCGSQFKTQRGLGKHQSHRHPAEVNAKRVAALPTKR LAWTQEDDEALKRHSDRLWQTGMTKTKLYPLLLPYFPERSLEAIKKRLLLTHWVPPNETPEL NPPPEHPERPGSPDRSQPPNQQPPMSPVAPPLNGLGSGNATSWRGNILASAADHLKESRMGS EELAQIARDIQTGVISRKQCRSRLNQHAKSWFPHKWKPSVNRAVETNRQWSKKAIRRANYAE VQKLYKLRRRDAASTVLSGHWRNAYKGPAPVPPEMEEYWAAVFKTPSAVDDRAPAEPPAVLW SLITPIAPSEVTAALNGMKASAPGLDRISAMELLSWDQPSLAAYYNLLLVAGGPPKHLSCSR 213 WFIPKTEDPKTPGDYRPISIASTILRAFHKILAWRLRDTLQLSPLQHAFLQRDGCLEASTL LHTILRRVHTDRVPCAMLFLDVAKAFDTVSHMSLFRVAYEAGLPPPLVSYLRHLYKKSTVRL AETTKCGRGVRQGDPLSPLLFIMVIDDIIKSSLPDIGFDFDGQRVGSLAYADDLVLFAERST RLQEKLQLLSEALQRAGMAENAKKSHGLTVARDGKRKCMA1VPTTYECKGETIKPLGTDDSV RYLGLQFNWKGRIIPKHTGMLHSLLNELSKAPLKPHQRLKLLSAHLVPKFTHELVLGHAHRN TLKRLDCLTRAAVRAWLRLPTDTPVGYFHAHVLDGGLGLPCFSTTIPLLQQKRLEKVASNPA TLFQIVQRQTSFQTLGRRIDRPCRLGGSVVTTKAEVREGWQIMLSNSVDGKELSISEVDKAS HEWLRHPARVYPRLYIRGIQLRGGLLPTKARSARGNNRQVTDRTCRGACCAPETQNHILQVC EVTHDARCARHNRVLRCLEKLLRRKDLHPRLEPVIPSGASFIKPDLIVEVMNQLWILDVSIV AGYRVEETWDIKASKYGRPDRVADIRRWAAVPATTPVIQLPWISNRGLCYRPSGDGLRALG LSRRDTMDLCILAIIGSLKCFDLYQRGTKDWNV (54) R2MasLat RT CSRWFIPKTEDPKTPGDYRPISIASTILRAFHKILAWRLRDTLQLSPLQHAFLQRDGCLEA STLLHTILRRVHTDRVPCAMLFLDVAKAFDTVSHMSLFRVAYEAGLPPPLVSYLRHLYKKST VRLAETTKCGRGVRQGDPLSPLLFIMVIDDIIKSSLPDIGFDFDGQRVGSLAYADDLVLFAE RSTRLQEKLQLLSEALQRAGMALNAKKSHGLTVARDGKRKCMALVPTTYECKGETTKPLGTD DSVRYLGLQF 214 (54) R2MasLat 5'UTR TTAAGAAGAGCGTAGTTGCAGGCTTGGGCACCTCCACGTGGTGACCGCTGGATATGGTACTT CGGTACCAGAACTAAGATCCAAGCCACCCCTCTACACGACTTTGCTTTGTAGAGGGTTAGTT ACTGGTTTACGTATTGGTTTTCGTGTTAGTCCAAGTCCCTCTGGAACT 215 (54) R2MasLat 3'UTR TATGTCTTGTTATACCTATGCTTGTATGTTGTTACCTGTCTATTAGCGAGCAATCGCACTTA GAGGGCCTGGCGGGCGGGAAAGGTCTAGTCGGTTGTATTTGCTGTATTAACATGTATACAAT GTATATTGATACCATGCAATGTGATGTATCTTGTGATATCGTATTATGCACTGCTTTACCCT GTAC TGTTTTGCCTTGC TTAAT C TAAAAATAAAGTGTAAAA 216 (55) R2MasLat2 ORF MDPSNTDGNASSVGTQDNNNARSSYLCFCGSKFNSERGLGKHQAHRHPAEVNAKRVAALPTK RLMWTQEDDDALKRHSDRLWQMGMTKSRLYPLLLPFFPERSIEAIKKRLLITNWAPPIITSE LNPHEHPERRTNPERRTNLERLAHPKELTNPDRAAPLTQQPPTSPVAHPPNGLGSGNATSWR GNILASAAVHLKENRMGDEELAQIARDLQTGAISRKQCRSRLNQHAKRWFPHTWKPSATKTV KANRQWSNKAIRRANYAQVQKLYKLRRRDAASTVLSGRWRNAYKGQAPVPPEMEEYWAKVFN TPSAIDNSAPAEPSAVLWSLITPIVPSEVTAALNGMKASAPGLDRLPATELLSWDQPSLAAY YNLLLAAGGPPEHLSCSRWFIPKTEDPKTPGDYRPISIASTILRAFHKILAWRLRDTIQLS PFQHAFLQRDGCLEASTLLHTILRRVHTERVPCAMLFLDVAKAFDTVSHMSLFRVAYEAGLP PPLVSYLRHLYKKSTVRLADTTKCGRGVRQGDPLSPLLFIMVIDDI IKS SLPDIGFDFDGLR VGS LAYADDLVLFAE KS TRLQEKLQLL SE ALERAGMALNAKKS HGITIAKDGKRKCMALVPT TYECKGETIKPLGTDDSVRYLGLQFNWKGRIIPKHTGMLDSLLNELSKAPLKPHQRLKLLSV HLVPRFTHELVLGHAHRNTLKRLDCLTRAAVRRWLRLPTDTPVGYFHAHVLDGGLGLPCFST TIPLLQQKRLEKVASDPATLFQIVQRQASFQTLGRRIDRPCRLGGSAVTTKAEVREGWQIML SNSVDGKELSIPEVDKASHEWLRHPARVFPRLYIRGIQLRGGLLPTKARSARGNNRQVTDRT CRGACCAPETQNHILQVCELTHDARCARHNRVLRHTEKLLRRKGLRTRLEPVIPSGASFIKP DLIVEMTDQLWILDVSIVAGYRLEDTWDIKASKYGRPDRVTDIRRWAAVPDTTPVTQLPWI SNRGLCYRPSGDGLRTLGLSRRDTMDLCLLAILGSLKCFDAYKRGTKDSNI 217 (55) R2MasLat2 RT CSRWFIPKTEDPKTPGDYRPISIASTILRAFHKILAWRLRDTIQLSPFQHAFLQRDGCLEA STLLHTILRRVHTERVPCAMLFLDVAKAFDTVSHMSLFRVAYEAGLPPPLVSYLRHLYKKST VRLADTTKCGRGVRQGDPLSPLLFIMVIDDIIKSSLPDIGFDFDGLRVGSLAYADDLVLFAE KSTRLQEKLQLLSEALERAGMALNAKKSHGITIAKDGKRKCMALVPTTYECKGETIKPLGTD DSVRYLGLQF 218 (55) R2MasLat2 5'UTR TTAAAAAGAGTGTAGTTACAGGCTTGGACACCTCCCAGTGGTGACCGCCGGATATGGTGCTT CGGCACCAGAGCTAAGAGCCAAGCCACCCCTCTACTTGACGATCGCTCTTGCAGAGGGTCTG TTACTGGTCTACTAAATATCAATAGTAATAGTCCTAGTCCCCCCGGAACT 219 (55) R2MasLat2 3'UTR TTATGTCTTGGACTTACGTTTTTGTGTTGTTACCTATCTCCTAGCGGAAATCGCACTTAGAG GGCCTGGCGGGCGGGATGGTCTTGCCGGTTGTATTTGTATTCCATATATGATGCACTGCTTT ACCATGTACCGTTTTGCCTTGCTTTTCTAAAAATAAACAGTCAAC 220 (56) R20xyLep ORF MSAKVSPSPSGPLDSSSIDNDAMNTVAEDRAQHPSFPCFCGLCFTTKQGLGQHQAHRHPAEV NAKRVAALPSKRLAWTLEDDETLRRHADGYWEKGMMKKTLYTLLAPRLPGRSQEAIKKRLQI LKWAPPSEHPERLDNPERETVQRAKGAPPSEHPERPDNPDRGAVHPECNTIPTPTASQPVAN PLTHEPDSTVDAAATWRRALLVAAAGRFRENKMGARELTQAARDLQNGVTSKKQCRARLNQH AEKWFPHKWKPSVARPETANRKWSKKAIRRANYANIQKLYKLRRRDAASTVLSGRWRNAYKG PAPMPAEMEEYWASVFETPSANDDSAPAEPSAVLWSLMDAIVPSEVTAALHGMKTSAPGLDR IPAEELLTWDQPSLAAYYNLLLAAGGPPKHLSCSRWFLPKTDTPSAPGDYRPISIASTILR AFHKIMARRLRDTLQLSPLQHAFLQRDGCLEATTLLHSIFRRIHMDRVPCAMLFLDVAKAFD TVSHKSLFRVAYEAGLPPPLVSYLRHLYSKSSVRLANKDTNCGRGVRQGDPLSPLLFILVID DIIRSSLPEVGFDFNGQRVGYLAYADDLVLLAEKS SRLQEKWLLCGALQKAGMAUSTAKKSH GLTFAKDGKRKCMALLPTPYECKGEPINPLGTGDSVKYLGLQFNWKGRVCPKHTGKLDFALQ ELTKAPLKPHQRLKLLTLHLVPKFTHELVLGFAHRKTIKKLDCLTRAAVRKWLRLPTDTPVS 221 YFHAHVRDGGLGLPCFSTSIPLLQRKRFEKVASNPDTLFQIVQRQDSFRSSGRRVDQPCRLN GAVLTSKTEVREEWKAVLHQSVDGKELSAPEVDKASHEWLRRPDRMFPRLYIRGIQLRGGLL STKARSARGKNRQVTDRTCKGACRAPETLNHILQVCEITHNARCARHNRVLRCLEKELRRAD AQTRMEPVIPSGSTFIKPDLIVEAANQLWVLDVAVVAGYRMEETWTLKTTKYGRPDRVEDIC RWAARPATTQVHHLPWISNRGLFYQPSAEGLKALGLSQRDLMDLCILAITGSLKCYDLYQH GSMTWGCK (56) R20xyLep RT CSRWFLPKTDTPSAPGDYRPISIASTILRAFHKIMARRLRDTLQLSPLQHAFLQRDGCLEA TTLLHSIFRRIHMDRVPCAMLFLDVAKAFDTVSHKSLFRVAYEAGLPPPLVSYLRHLYSKSS VRLANKDTNCGRGVRQGDPLSPLLFILVIDDIIRSSLPEVGFDFNGQRVGYLAYADDLVLLA EKSSRLQEKLDLLCGALQKAGMALNAKKSHGLTFAKDGKRKCMALLPTPYECKGEPINPLGT GDSVKYLGLQF 222 (56) R20xyLep 5'UTR CTTGCCCCACGCCTCCCAGGGTTTGGACGCCTCCACGTGGCGACCGCTGGATAAGGGGTGGT GGTCCCAGACTATCCACACCCGAACCAAGAGCCAAACCACCCTCCTGCGGCCCCTAACACAC C GCAGGAGGAC TGCT GC TGGT CAATAAA 223 (56) R20xyLep 3'UTR GGAGTACTCGGTGACGGCGTAACAGGCTGAAATTGTCTTCTAGCGATGCAAATCGCCTTAGA TAACTTGGTGGGAAGGGGGGCTTTGCGCGCGGAATGTGCTCTGCCATGTACCTGTACCGCCT T GT TAG T C TAAAAATAAATGT TAG 224 (57) R2PanAII ORF MDPSNKDGNASSAGTQDTNTRPSYRCFCGSQFNTQRGLGRHQAHRHPAQVNALRVAALPTKR LAWTQEDDEALKRHSDRLWQSGMTKTKLYPLLIPYFPERSLEAIKKRLLLTHWAPPIETSEQ NPPQEHPERPENPDRPPTIQQPPTSPVAPPQNGPGCGNATSWRGAILASAADRLKETKMGGE ELAQIARDIQTGVISRKQCRARLNQHAKSWFPHKWKPSVTRPAGANRQWSKKAIRRANYAEV QKLYKLRRRDAASTVLSGRWRNAYKGPAPVPPEMEEYWAAVFKTPSAIDDRVPAEPPAVLWS LITPIVPSEVTAALNGMKSSAPGLDRLSATELLSWDQPSLAAYYNLLLAAGGPPKHLSCSRV VFLPKTEDPKTPGDYRPISIASTILRAFHKIMAWRLRDTLQLSPLQHAFLQRDGCLEASTLL HTIFRRIHTDRVPCAMLFLDVAKAFDTVSHMSLFRVAYEAGLPPPLVSYLRHLYKKSTVRLA ETTKCGRGVRQGDPLSPLLFIMVIDDIIKSSLPDIGFDFDGQRVGSLAYADDLVLFAERSTR LQEKLDLLSEALQRAGMALNAKKSHGITIARDGKRKCMALVPTPYECKGDAIQPLGTDDSVR YLGLQFNWKGRIIPKHTGMLDSLLNELSKAPLKPHQRLKLLSVHLVPKFTHELVLGHAHRNT LKRLDCLTRAAVRHWLRLPTDTPVGYFHAHVLDGGLGLPCFSTTIPLLQQKRLEKVASNPAT LFQIVQRQTSFQSLESRVDRPCRLGGTWTTKAEVREGWQIMLSNSVDGSELNISEVDKASH EWLRHPARVYPRLYIRGIQLRGGLLPTKARSARGNNRQVTDRTCRGACCAPETQNHILQVCE LTHDARCARHNRVLRCLDKLLRRKGLRTRLEPVIPSGASFIKPDLIVEVMNQLWILDVSIVA GYRVEETWVIKTTKYGRPDRVADIRRWAAVPATTPWQHPWISNRGLCYRPSGDGLRALGL SHRDTMDLCLLAIMGSLKCYDLYQRGTKDWNV 225 (57) R2PanAII RT CSRWFLPKTEDPKTPGDYRPISIASTILRAFHKIMAWRLRDTLQLSPLQHAFLQRDGCLEA STLLHTIFRRIHTDRVPCAMLFLDVAKAFDTVSHMSLFRVAYEAGLPPPLVSYLRHLYKKST VRLAETTKCGRGVRQGDPLSPLLFIMVIDDIIKSSLPDIGFDFDGQRVGSLAYADDLVLFAE RSTRLQEKLDLLSEALQRAGMALNAKKSHGITIARDGKRKCMALVPTPYECKGDAIQPLGTD DSVRYLGLQF 226 (57) R2PanAII 5'UTR TTAAGAAGAGCGTAGTTGCAGGCTTGGGCACCTCCTCGTGGTGACCGCTGGATATAGTACTT CATGTACTAGAACTAAGATCCAAGCCACCCCTCTACACGACTTTGCTTTAGTAGAGGGTTAG TTACTGGTTTACTTATTTATATATCGTACCAGTCCAAGTCCCCCTGGAACT 227 (57) R2PanAII 3'UTR TAT GT C T T GT AAT GC T TAT GC T T GT AT GT T GT TAG C T GT C TAT T AGC GAGC AAT C GC AC TT G GAGGGCCTGGCGGGCGGGAAAGGTCTAGTCGGTTGTATTTGCTATATAAACTTGTATACCAT GTATATTGATACCATGCATATGTGATGTATCTTGTTGTATCGTATTATGCACTGCTTTTCCA TGTACTGTCTTGCCTTGCTTAAACCAAAAATAAACTGTATCC 228 (58) R2PanGut ORF MDPSNKDGNASSAGTQDTNTRPSYRCFCGSQFNTQRGLGRHQAHRHPAQVNALRVAALPTKR LMWTQEDDEALKRHSDRLWQSGMTKTKLYPLLIPYFPERSLEAIKKRLLLTHWVPPIETSEQ NPPQEHPERPENPDRPPTIQQPPTSPVAPPQNGPGCGNATSWRGAILASAADRLKETKMGGE ELAQIARDIQTGVISRKQCRARLNQHAKSWFPHKWKPSVTRPAGANRQWSKKAIRRANYAEV QKLYKLRRRDAASTVLSGRWRNAYKGPAPVPPEMEEYWAAVFKTPSAIDDRVPAEPPAVLWS LITPIVPSEVTAALNGMKSSAPGLDRLSATELLSWDQPSLAAYYNLLLAAGGPPKHLSCSRV VFLPKTEDPKTPGDYRPIS IASTILRAFHKIMAWRLRDTLQLSPLQHAFLQRDGC LEAS TLL HTIFRRIHTDRVPCAMLFLDVAKAFDTVSHMSLFRVAYEAGLPPPLVSYLRHLYKKSTVRLA ETTKCGRGVRQGDPLSPLLFIMVIDDI IKSSLPDIGFDFDGQRVGSLAYADDLVLFAERSTR LQEKLDLLSEALQRAGMALNAKKSHGITIARDGKRKCMALVPTPYECKGDAIQPLGTDDSVR YLGLQFNWKGRIIPKHTGMLDSLLNELSKAPLKPHQRLKLLSVHLVPKFTHELVLGHAHRNT LKRLDCLTRAAVRHWLRLPTDTPVGYFHAHVLDGGLGLPCFSTTIPLLQQKRLEKVASNPAT LFQIVQRQTSFQTLESRMDRPCRLGGTWTTKAEVREGWQIMLSNSVDGSELNISEVDKASH EWLRHPARVYPRLYIRGIQLRGGLLPTKARSARGNNRQVTDRTCRGACCAPETQNHILQVCE LTHDARCARHNRVLRCLDKLLRRKGLRTRLEPVIPSGASFIKPDLIVEVMNQLWILDVSIVA GYRVEETWDIKTAKYGRPDRVADIRRWAAVPATTPWQHPWISNRGLCYRPSGDGLRALGL SHRDTMDLCLLAIMGSLKCYDLYQRGTKDWNV 229 (58) R2PanGut RT CSRWFLPKTEDPKTPGDYRPISIASTILRAFHKIMAWRLRDTLQLSPLQHAFLQRDGCLEA STLLHTIFRRIHTDRVPCAMLFLDVAKAFDTVSHMSLFRVAYEAGLPPPLVSYLRHLYKKST VRLAETTKCGRGVRQGDPLSPLLFIMVIDDIIKSSLPDIGFDFDGQRVGSLAYADDLVLFAE RSTRLQEKLDLLSEALQRAGMALNAKKSHGITIARDGKRKCMALVPTPYECKGDAIQPLGTD DSVRYLGLQF 230 (58) R2PanGut 5'UTR GAAGAGCGTAGTTGCAGGCTTGGGCACCTCCTCGTGGTGACCGCTGGATATAGTACTTCATG TACTAGAACTAAGATCCAAGCCACCCCTCTACACGACTTTGCTTTAGTAGAGGGTTAGTTAC TGGTTTACTTATTTATATATCGTACCAGTCCAAGTCCCCCTGGAACT 231 (58) R2PanGut 3'UTR TAT GT C T T GT AAT GC T TAT GC T T GT AT GC T GT TAG C T GT C TAT T AGC GAGC AAT C GC AC TT G GAGGGCCTGGCGGGCGGGAAAGGTCTAGTCGGTTGTATTTGCTATATAAACTTGTATACCAT GTATATTGATATCATGCATATGTGATGTATCCTGTTGTATCGTATTATGCACTGCTTTTCCA TGTACTGTCTTGCCTTGCTTAAACCAAAAATAAACTGTATCC 232 (59) R2VipUrs ORF MIPCIDDPRPPGPPDRSSPGRRSRVACRESDAKDPGHVCPCGSEFQSKQGLAMHRYHRHMAE ENAKRLASLPSKKLAWSQEEDRALLRLATAQWKGGMAKVTLYGLLQPQFPGRSVEAIKKRLQ GLKWTAPADTPEREPLPMPPRAAQGDVEPATSPAPTADPTVFNQNTDDPTVSWRRALLTAVE GKLSEPKMGADTLRRIASQLKSGEINGEACRALMNEHAREWFPHMWKPSLVKDQTDTRCWSK RAVRRANYAKVQRLYKLQRRDAANTVLSGRWRNAYRGQAPLPKGMDQYWSKVFEAGSAKDEK AQVVPDKTLWETLAAVTPSEVTSALKGMKASAPGLDRISAEDLLAWNQPSLAAYFNLMLAAG GPPEQLACSRVTFIPKVDEPKTPGDYRPISIASVILRAFHKILAWRLRDTVQLSPFQHGFLQ RDGCLEASALLHTILRKSHRDRKPCAMLFLDVAKAFDTVSHQTLFRVATAMGLPPPLVDYLK HLYGRSTVQIAGQNTKCGRGVRQGDPLSPLLFIMVMEDIVRDSLPEVGFDLDGQRVDSLAYA DDLVLLAEKPSRLQEKLTLLTAALQNAGMELNARKSHGLTIEKASKRKCMVLSDTKYQCKGE GIQPMGTDDSVRYLGLHF1WKGRLVPKHTGKLDSLLKELSAAPLKPFQRLQLLKLHVVPKFV HELVLGHAHRNTLQKLDCLTRAAVRQWLRLPTDTPLGYLHANIKDGGLGIPCFSTSIPLLQQ KRFEKIAQNPATIFQIIQRQDSFRTLGRRLDRPCRLQGAVLTSKAEAREEWGNVLSNSVDGR ELRYPDVDKASHEWLLRPSRVFPRLHMRGIQLRGGLLPTKARSARGNNRQVKDKTCRGACHQ PETLNHILQVCEVTHDGRCARHNRVLHRLAQLLRKKGVRTTLEPVIPSGSSFIKPDLIIETD TQTYVLDVSWAGGRMKTSWDIKDEKYGRPDRVNDIRKWGAIPEASRVCQLPVIISNRGLCY QATGEGLRALGLTTREISDLCLLAISGSLKCFDLYMRGTRGVRRAPEHR 233 (59) R2VipUrs RT CSRVTFIPKVDEPKTPGDYRPISIASVILRAFHKILAWRLRDTVQLSPFQHGFLQRDGCLEA SALLHTILRKSHRDRKPCAMLFLDVAKAFDTVSHQTLFRVATAMGLPPPLVDYLKHLYGRST VQIAGQNTKCGRGVRQGDPLSPLLFIMVMEDIVRDSLPEVGFDLDGQRVDSLAYADDLVLLA EKPSRLQEKLTLLTAALQNAGMELNARKSHGLTIEKASKRKCMVLSDTKYQCKGEGIQPMGT DDSVRYLGLHF 234 (59) R2VipUrs 5'UTR TCTCCCGTCGCTTGACATTGGCGTTTTTTCGCAGTGCGTTTATCAATTGCGAGAGCTAGTCT TTGTCCTTGACGTGAGTTGATTGCATAGTTGCACGGGTTAGACACCTCCTTGTGGTGACCGC TGGATAAGGCCCCGGGCCTGAACCAAGATCTAACCCACCCTCCGTTGCAGAAACAGCGGAGG CTAAACTGCTGCTA 235 (59) R2VipUrs 3'UTR GGAGCACCCTTAGGACTGCACTAGGCGGTGACCCCTCTGGTCGACACCTGGGCTAGCGACCA AGTCGCCTTAGAAGACCTGATGGGGGGGGTCTCCGTACCCTTTCTCGTCTTGTCTCTCTAAT AAT ACAT GT GAAAT 236 (60) R2FasGigl ORF LLSGGGSNRSPAAPRGVGPGRSSGANIGSNANGFLCDCGRSFGSRIGLGQHRRHAHSTQVNE ERTASVISRTRRGTWSTPDDESLVRLADTTFQPGMLRKDLCATLTSYFDGRSAESTKKRLQF LHWSPPTSVHLVEASEAPPTMDSQHLPEMVDQSAIDWTQRLVSDITSGLASGPGGVGPWAGL LGIITDWRDGVLDLQSARSALETLLAATFPHTWQSTPARTVRCVPTTKRGIRRLQYAHVQKL YATRRKDCAQTVLSGDWKEAHLRRSAPPSDLMAYWKGIFSQPSHPDPRPVQRPSATQWSVLD PILASEVSEALRLMGHTAPGLDRLTVRDLLQMDQNCIAQLLNALLVLRTPTHHLSMARVTLV PKCSNPTGPGDYRPIAVTSVMLRLLHKILARRWRSQLALSPWQMAFLQRDGCSEASTVLHTI LRSVHQDCTPLASIFVDVSKAFDLVSHETIIRAATMFGLPTPMVDYLRSLYTGSMVRLGDES IACSRGVRQGDPLSPLLFIAVMEEVLSNSAPTLGVSIGGTPVDHLAYADDLVLFADNADRLR ERLVALSTALASAGMSINGDKSVGLTIRKDGKNKRLILWPTAYEVNGVRVQPIGVDQQIKYL GLHFTWKGRIQPRSTAKLESMLVNITKAPLKPHQRLDILARFALPKLYHELVLGMAHRRTIK SMDVMVRARVRAWLRLPKDTVLGFFYAKRASGGLGLPNLSTTVPMAQRTRLERLARSSLAPA RMATSASPFHQLVRQANIPIRVAASVITSKADAISAWSADLLNSNDGRGLRNFPMDRASLLW LGTGDSVPPRLFLRATWLRGGLLSTKVRRARGYWSTEDLKCRGSCGTAESADHILQCCAAT HQVRCERHNKVVRWLASSLLKRGLRVMVEPIIPLVRSFCKPDLIVCCNDLVYVLDVCWSGQ SAESAWRTKVDKYSATPVEESIKRTLGLPTARLKHCPVLISNRGLLFKRSGSGLRRLGLRPF VLARACQLVVEGSLKTYDVYMKGL 237 (60) R2FasGigl RT MARVTLVPKCSNPTGPGDYRPIAVTSVMLRLLHKILARRWRSQLALSPWQMAFLQRDGCSEA STVLHTILRSVHQDCTPLASIFVDVSKAFDLVSHETIIRAATMFGLPTPMVDYLRSLYTGSM VRLGDESIACSRGVRQGDPLSPLLFIAVMEEVLSNSAPTLGVSIGGTPVDHLAYADDLVLFA DNADRLRERLVALSTALASAGMSINGDKSVGLTIRKDGKNKRLILWPTAYEVNGVRVQPIGV DQQIKYLGLHF 238 (60) R2FasGigl 5'UTR GGGTCATAGTTGCAGACCAGACCACCTCCTCGTGGTCCCGCTGGATAGGTCTTGTCTCGGCT TCGGCTGGGGCTTGGCTGAACCAAGTGTCTGGTCACCCCCCGTGTGGGCCAATCACCCACTC GGGGGTTTTGGGCTCGATTACAGAAACAAATACAAATACACAATCTCTCGACTCC 239 (60) R2FasGigl 3'UTR TGAGAATGGCCTGACTCGCCAGGTGAACATGGACCGGCTCCACCTATGACGTTCTGTGCCTA AACCTGCCAGGAGGTACAGAGCCGATGCAGAGGAGACGTTGGACGCGTATATATCAATCTCC AATCAGATGATGCGTGCTCTCCCATGAAAGACTTGCTTGCTCCCCCCTATCTTTCTTCACTG aattgttttctgaccccgtattgctgtattttctgattggacaataaatggtatca 240 (61) R2FasGig2 ORF LLSGGGSNRCPPAPREVGPCRSSGANIGSNENGFQCDCGRSFGSRIGLGQHRRHAHPTQVNE ERIASVISRTRRGTWSTADDESLVRLANTTFQPGMFRKDLCATLTSSFDGRSAESIKKRLQF LHWSPPASINLVEASEASPSSPPSADTQHLPEMVDESANEWTQRLVADITSGLANGPVGAGP WADLLGIITNWRDRVFDLQSARSALETLLAATFPHTWQSTPARMVRCVPTSKRGIRRLQYAH VQKLYATRRKDCAQTVLSGDWKEAHLRRSAPPTDLLAYWKGIFSQPSHPDPRPVQRPSVAQW SVLDPILASEVSEALRLMGTTAPGLDRLTVRDLMQMDQNYLAQLLNALLVLRTPTQHLSMAR VTLVPKCSKPTGPGDYRPIAVTSIVLRLLHKILARRWRNQLALSPWQMAFLQRDGCSEASTV LHTILRSVHQDCTPLASIFVDISKAFDLVSHDTIIRAASMFGLPAPMVDYLRSLYSGSMVRL GDESIACSRGVRQGDPLSPLLFIAVMEEVLSNSAPALGVSIGGASVDHLAYADDLVLFADNA DRLRERLAALSTSLAAAGMCINGAKSVGLTIRKDGKNKRLILWPTTYEVNGVRVQPVGVDQQ IKYLGLHFTWKGRIQPRSTAKLESMLVNITKAPLKPHQRLDILARFALPKLYHELVLGMAHR RTLKSMDVMVRARVRAWLRLPKDTVLGFFYAKRASGGLGLPNLSTTVPIAQRTRLERLARSS LAPARMATSASPFHQLVRQANIPIRVGASVITSKDDAVSAWSADLFNSNDGRGLRNFPMDRA SLLWLGAGDSVPPRLFLRATWLRGGLLSTKVRRARGYWSAEDLKCRGRCGAVESADHILQC CAATHQVRCERHNKVVRWLASSFLKRGLRVLVEPIIPLVPSFCKPDLIVCCDDLAYVLDVCV VSGQSAESAWRTKVEKYSTTPVEESIKRTLGLPTVRLKHCPVIISNRGFLFKRSGSGLRRLG LRPFVLARACQLVVEGSLKTYDVYMKGL 241 (61) R2FasGig2 RT MARVTLVPKCSKPTGPGDYRPIAVTSIVLRLLHKILARRWRNQLALSPWQMAFLQRDGCSEA STVLHTILRSVHQDCTPLASIFVDISKAFDLVSHDTIIRAASMFGLPAPMVDYLRSLYSGSM VRLGDESIACSRGVRQGDPLSPLLFIAVMEEVLSNSAPALGVSIGGASVDHLAYADDLVLFA DNADRLRERLAALSTSLAAAGMCINGAKSVGLTIRKDGKNKRLILWPTTYEVNGVRVQPVGV DQQIKYLGLHF 242 (61) R2FasGig2 5'UTR GGGTCATGGTTGCAGACCAGACCACCTCCTCGTGGTCCCGCTGGATAAGCCTTGTCTCGGCT TCGGCTGGGGCTTGGCCGAACCAAGTGTCTGGTCACCCCTCGTGTGGGCCAATCACCCACTC GGGGGTTTTGGGCACGATTACTGAAACTCATACAAATACACAATCTCTCGACTCC 243 (61) R2FasGig2 3'UTR T AAGAAAGGC C T GAC T C AC C AGAT GAAC AT GGAC C AAC T T C AC C TAT GAC GTT C T GT GC C AA ?\ACCTGCCAGGAGGTACAGAGCCGATGCAGAGGAGACGTTGGACGCGTATAT7\AC7\ATCTCC AATCAGACGTTGTGTGCTCTACCATGA?\AGACTTGCTTGCTCCCCCCATCTTTCTCTCTTGA ATTGTTTTCTGCCCCCATATTGCTGT7\AATTCTGATTGGAC7^ATAAATGGTATCA 244 (62) R2FasGig3 ORF LESPDSSRIDANRRLADSEEHGMNTCKCRWCSGSFRTRRGLTQHMRHAHPNELNAARLGSLR PKRKRWSKEEDTRLYELVDYRLGYTSIAALCREIADHFPGRSVEAIEARVAGLRRPGGNWGG MMERDQDNIVTLQVDEEDEHAETKRWEAKVLEAISETANGAEPERVGVLQWLARRFCDGRIS REAAAGELEAIVASWFPHTLKPRPRSEPPNAGQLSKKRVRRLQYAVLQRMYRKRRKDAVDMV LTGDWRSSHMPKRRTVPGLTAYWKEVFEVESAVDNRPTPRPASSLWAVIDPIQEGEVRKAIR EIGKSSPGLDGLTAADVGKLDNRLVLALLNVLLLLRSPPEALTKARITLIPKVVNPEKPAEY RPIAIASVITRILHKVLASRWSRSHSFADLQVAFQKRDGCCEASEILQAVLRRVHEKTKGLA AAFVDISKAFDTVATSTIIRNAVAQGLPPPLVEYIRHMYDTSAVLIEQETVRPGRGVRQGDP LSPLLFLSVMDEMLKSSLPGVGFDQGGRLVDALAYADDLVLFAEDESRLRDKLEALNSALQA AGMSLNASKSCTLTIVPDGKRKTWLAPTQYSVGGTRLRTMNVEDRVKYLGLEFNWKGKVRV RHTGILERYLIEVTRAPLKPYQRLTVLKQHLVPKLLHQLVLGAAHRNTLASMDRMIRQFVRG WLRLPADVPVAYLYTKIPDGGLGLPSLATLVPLAQRKRTEKVASSSAATAVLFKDTPCFKQF VARANMGIRIGGEAVCSKAEASQAWSEQLWKSHDGKALRGESVDPVSHDWVRDPTRLPGKVF LRGIKLRGGLLPTRTRASRGGRTPAHGVMCKGGCGHPESIDHILQSCQLTHNVRCERHNRVL RKINKVLNRKCEKVWLEPIVPCENS FRKPDLWRERGWYVVDVCVTTSARMEETRRLKVQK YGTESVTGAVRDLAGWESARWQAPVVITNRGLLSKESGSSLRNLGFTRSELSDLAMTVIL GSLKGYDLYMRGTRRY 245 (62) R2FasGig3 RT KARITLIPKWNPEKPAEYRPIAIASVITRILHKVLASRWSRSHSFADLQVAFQKRDGCCEA SEILQAVLRRVHEKTKGLAAAFVDISKAFDTVATSTIIRNAVAQGLPPPLVEYIRHMYDTSA VLIEQETVRPGRGVRQGDPLSPLLFLSVMDEMLKSSLPGVGFDQGGRLVDALAYADDLVLFA EDESRLRDKLEALNSALQAAGMSLNASKSCTLTIVPDGKRKTVVLAPTQYSVGGTRLRTMNV EDRVKYLGLEF 246 (62) R2FasGig3 5'UTR CTGGGTCGGGCTAATTACCCCTCCTTGGTTCATGTCGCCTATCAATTCCGTTAAACAATAAA AGAATATTTTTATCTCAAAAC 247 (62) R2FasGig3 3'UTR TGAGAGATCTGGGGCGGAACGTCACGTGGGTCTGTGAAGTTTGCTGTACCATGGCTGGTACC AGCCTCTGTTGAAAGAGTGCGCTGTTGGGGACAGCGGCGCACTTTCTGCTTCACGCTGGCAA 248 CCGCATGAGTCCACCTATGGATCGGCCCACGTGTACTAACTTAAAGCGCGTCACACGAAAAT GCTCACTACGGGTTGAAGTCTCTTGCTCTGTAACTGTGCGAAACCGTCGGTAAGCAGCTTTG CTGCCTCCAGATGACGCGTAGAGTGTACCCACTGGAAAGTATCGCGAGTGCTTGCCGGATAG ATGTAGACCGGCTGGAATGATGTTTATTGAAGCCTAATGTCATCTGGAAAACTTCCCGTAGA C (63) R2FasGig4 ORF MSTHNANGAASATPMASSSQPMEYICEICGKSCRSKAGLTLHKKVHPPPTHPPLPPTPPTPK AFQCVLCSDSFHTKMGLTQHKRHRHLQEYNGDKRQQIVTSARSRRWTTSEEAALIALANDLA ATHSEKQELCAALSTQFPNRSAESIKKRLQHLDWQYPDDVLPDSTSSDDDTNTSNLSSDSIS MLQPLPNSPTDSEPVAPQPTTSLCATSTALLEAACSLLRSTPHDVFGSRELLSIVEAGLTHS MDATALRCRLEAHAEANIPNLWNPSRPRSSRLPTRPLSRRPRKPPRPKILARRAQYAHLQCL FAQRKKDAAREVLSGRWRSAHENDSSWSPDFTRFWSEKLSLPPLNDPRPHRQLSHPPSLILH PITIPELQDALRDMRGSAPGIDRVTPETLLRSPLSVFTAYINILLALAHVPRRLNTARITFV PKSDNPTSPSDYRPISVSPVLLRSLHKVLQRRWTSLFPVDGLQFAFLKRDGAFEATALLHTL LRYAHTSFHSLAFASLDLSKAFDSISHDSILRSAATFGAPPILLDYVRSSYATASCVLPDGS TITPRRGVRQGDPLSPLLFIMAIDEILSLSHPQTSFLTPSGPVDAIAYADDLILFADSADGL QKKLSDCSVACGMSGLVFNTQKSFSASIITSPKQKISALDETTLFVNGHPIRTLSTSDTFSY LGTSFTYRGKAGVDYSNTLRIMLQDVISAPLRPFQRLYILRSHLISRLHHTLCLGVIHKKTL KRLDLQVRHCTRKFLRLPKDTPTAYFHARCSDGGLGIPELSSQIPLIRRKRLERLLSSTAPL LRWAGTCPAASSSQAISHVPIAVQGAYIQSKEQAADAWKNSLYGTLDGKHISCQQFAAPSDL WITSPTRMFPRDFIHNIKLRCHLLSTKTRRCRGLRSADDILCRGGCGQPESLSHILQSCSIT HDSRCRRHDDVVNLLLKRLMRMGATCYNEPRIPLETTFCKPDVTVVKGNTAFVCDTAVCDPS LIQQTLTNKVAKYSTPVVNTAIQSFLSASGHATPNIVHKPIVITYNGFVHRSSASTLRQFHL SPLDILDLVSTTMRGSTKTYLRYMRGPN 249 (63) R2FasGig4 RT IDRVTPETLLRSPLSVFTAYINILLALAHVPRRLNTARITFVPKSDNPTSPSDYRPISVSPV LLRSLHKVLQRRWTSLFPVDGLQFAFLKRDGAFEATALLHTLLRYAHTSFHSLAFASLDLSK AFDSISHDSILRSAATFGAPPILLDYVRSSYATASCVLPDGSTITPRRGVRQGDPLSPLLFI MAIDEILSLSHPQTSFLTPSGPVDAIAYADDLILFADSADGLQKKLSDCSVACGMSGLVFNT QKSFSASIITSPKQKISALDETTLFVNGHPIRTLSTSDTFSYLGTSF 250 (63) R2FasGig4 5'UTR TTCCTTTCACTGCTAATTTTCGTGAAATTCCGTCTATATGAGTCACTCACTATGATGTCGCT CGCTACCTCTGGATTTGTTTTTTTTTTGTTTTTGTTTTGTTTGTTTTGTTGCTGTTTGTTTC TTTGCTCTTTTTAACTCACACACACATGTGCTGGTCCTCGCACCTATCACACACACACTACC CTATGCCAGTTACCCGCCAGTCTAAGGAATATAGACGCCGGCCGTAACTTGAACACCCTGTG ATTACCCCATATGCTTCGGGTTGGTCTTCGTGAAGAAGCCGAAGCTAGGGTCTGCTTCCAAA GCTGCCCTACACACCTGTGTTGGTGCCGTCCGTGATACTCACGTCCGCCACCTTTTTTTCTT TCGCTGGCC 251 (63) R2FasGig4 3'UTR TGACACGACATCCCAACCCATCTCAACACCTCAATGTTCACACACTTGCACTTTTCCACCGA CTCGCACAACCATTCCGCGAGCGCACATATATATTCCGATTCGGTGACAAAATTACTGTACT GTGTACAGCGCTTGTCAAACGCAATGTCAAAACCGCTTTATTTGACCTATGTTTGACAAAAA TATATGTTTC 252 (64) R2FasHep ORF LVFVKKPKLGSASKAALHTCVGAVRDTHVRHLFSLAMSTHNANGAASATPMASSSQPMEYIC EICGKSCRSKAGLTLHKKVHPPPTHPPLPPTPPTPKAFQCVLCSDSFHTKMGLTQHKRHRHL QEYNGDKRQQIVTSARSRRWTTSEEAALIALANDLSATHSEKQELCAALSTQFPNRSAESIK KRLQHLDWQYPDDVLPDSTSSDDDTNTSNLSSDSISMLQPLPNSPTDSEPVAHQPTASLSAT STALLEAACSLLRSTPHDVFGSSELLSIVEAGLTHSMDAAALRCRLEAHAAANIPNLWNPSR PRSSRLPTRPPSRHPRKPPRPKVLARRAQYAHLQCLFAQRKKDAAREVLSGRWRSAHANDSS WSPDFTRFWSEKLSLPPLNDPRPHRQLSHPPSLILHPITIPELQDALRDMRGSAPGIDRVTP ETLLRSPLSVFTAYINILLALAHVPRRLNTARITFVPKSDNPTSPSDYRPISVSPVLLRSLH KVLQRRWTSLFPVDGLQFAFLKRDGAFEATALLHTLLRYAHTSFHSLAFASLDLSKAFDSIS HDSILRSAATFGAPPILLDYVRSSYATASCVLPDGSVITPRRGVRQGDPLSPLLFIMAIDEI LSLSHPQTSFLTPSGPVDAIAYADDLILFADSADGLQKKLSDCFVACGMSGLMFNTQKSFSA SIITSPKQKISALDNTTLFVNGHPIRTLSTSDTFSYLGTSFTYRGKAGVDYSNTLRTMLQDV ISAPLRPFQRLYILRSHLISRLHHTLCLGVIHKKTLKRLDLQVRLCTRKFLRLPKDTPTAYF HARCSDGGLG1PHLSSQIPL1RRKRLERLLSSTAPLLRWAGTCPAASSSQAISHAPITVQGA YIQSKEQAADAWKNSLYGTLDGKHISCQQFAAPSDLWITSPTRMFPRDFIHNVKLRCHLLST KTRRSRGLRSADDILCRGGCGQPESLSHILQSCSITHDSRCRRHDDVVNLLLKRLMRMGATC YNEPRIPLETTFCKPDVIVVKGNTAFVCDIAVCDPSLIQQTLTNKVAKYSTPVVNTAIQSFL SASGHATPNIVHRPIVITYNGFVHRSSASTLRQFHLSPLDVLDLVSTTMRGSTKTYLRYMRG PN 253 (64) R2FasHep RT IDRVTPETLLRSPLSVFTAYINILLALAHVPRRLNTARITFVPKSDNPTSPSDYRPISVSPV LLRSLHKVLQRRWTSLFPVDGLQFAFLKRDGAFEATALLHTLLRYAHTSFHSLAFASLDLSK AFDSISHDSILRSAATFGAPPILLDYVRSSYATASCVLPDGSVITPRRGVRQGDPLSPLLFI MAIDEILSLSHPQTSFLTPSGPVDAIAYADDLILFADSADGLQKKLSDCFVACGMSGLMFNT QKSFSASIITSPKQKISALDNTTLFVNGHPIRTLSTSDTFSYLGTSF 254 (64) R2FasHep 5'UTR TTATTAAAATATCTTCGCCTCGAACGTTTACTGTGCGCTTAGCCTCATTTTGAGACTATTTG TGCAGTTTTCCATACTGTATTTCATTCCGTCGACCCTCTCATCCCACGGCCGAACCTCAACG AGGCTGCACAGGCCATTCTTCAGTACTTTCACCACTTTTTCTCCAAATTGTCCACTCTTGTG CCTCCGACTGGTCACTTTCAGTTTCTTTATCACTAATTCCGCCTAGAAACGGTCTTTTTGAC ATAACTTATATATATAAGTTTTGTGCAATTTCCATTTTTGTCCCTTTTTTCACCCTTGACGA GGGCACATCACGCCACTGCTCCTCCTTGCTAAACGCGGGAGTATTATTAAAATATCTTCGCC TCGAACGTTTACTGTGCGCTTAGCCTCATCTTGAGACTATTTGTGTAGTTTTCTATCGGATA CTGCATACAGGCATTTCCTTTCACTGCTAATTTTCGTGAAATTCCGTCTATATGAGTCACTC ACTATGATGTCGCTCGCTACCTCTGGATTTGTTTTTTTTTTTGTTTGTTTGTTTTGTTGCTG TTTGTTTCTTTGCTCTTTTTAACTCACACACACATGTGCTGGTCCTCGCACCTATCACACAC ACACAACCCTGTGCCAGTTACTCGCCAGTCTAAGGAATATAGACGCCGGCCGTAACTTGAAC ACCCTGTGATTACCCCATATGCTTCGGG 255 (64) R2FasHep 3'UTR TAACACGACATCCCAACTAATCCCAACACTTCCAAGTCCACACATTTGCACTTTTCCATTGA CTCGCACAACCATTCCGCGAGCGCACAAATATATTCCGTTTTGGTGACAAAATTACTGTACT GTGTACAGCGCTTGTCAAACGCTATGTCAAAACCGCTTTATTTGATTATGTTTGACAAAAAT ATATGTTA 256 (65) R20piVivl ORF MGWHANDGNAVCNICGLSFRTVRGLGQHKRHRHPIELNDERTKLLPRRKGEWSEYESMKLAR LADEMASSFQTKAELYAALAAKFAGRSAEAIKKRLIKIGWSGITKYKTETGPKRGPESLPKI TEGGIDGLSDDDSDCTDWRNALLVCIADGIRQAEKHPDARALGDIAEGMLSGEMSVDQARMR LASWDRMFPEVWTPHRGAMRRHVPKTKKAQRRATFARLQSLFKRKRKEAAKCVLDGQWQEL WKCDETKPEGTVDYWKGVLGAEAHLDARPVPTAVQKWSILSPITSAEVTGALKESVGSSPGM DKKDARELLTWNPIILAQLLNLFLVTELPPRTLSRARISLIPKTVSPASPGDYRPIAISSVV LRLLHKLLFRRWRKVVKLESIQFAFQERDGCLEASSLLNAILHSVHDTVRPIAAAFLDISKA FDRVSHDTILRAAQAHGAPMPLVRYLRRLYSDGWNLNGEDIKSKRGVRQGDPLSPLLFVMV MEEWKQCCPEFGYNLEGTRIGALAYADDLVLLAPSRFELEEKLNGLTSALAAAGMELNSAK SAVMIVEKSGKHKTLAIVPGSLQVGSEAIKCLGPTDAVKYLGLRFNWKGRLRTKAGTLFQEM LSNISRAPLKPYQKFEMLKEFATPRLQYELVLGSAHRNTLKALDVAARHAVRAWLRLPKDTP LGFFYAKVKDGGLGLTSFATTIPLLQRKKLQRIASSPDPWRGLLKAKNVLSEQKLAYIPVR AKDTLVSSADEVSQAWRVDLKSSMDGRELVTDSVDRASFDWLANPRTVLPRLFIRGVQLRAG VLGCKARNARGRSVASGDLLCRGRCGVAETLSHILQRCQVTHDARCARHNRLVHNLAGRLSR RGYEVMTEPIIPVGRTFCKPDLVVRHEEHAYVLDVTVTRGQRLAESWNLKTTKYGLKEVETY IRSNLFGRTLGDVRHLPWFTDRGLLCERSGKGLRSLGLTTKELSVLCLLAVRGSLACYDVY MRGT 257 (65) R20piVivl RT RARISLIPKTVSPASPGDYRPIAISSVVLRLLHKLLFRRWRKVVKLESIQFAFQERDGCLEA SSLLNAILHSVHDTVRPIAAAFLDISKAFDRVSHDTILRAAQAHGAPMPLVRYLRRLYSDGV VNLNGEDIKSKRGVRQGDPLSPLLFVMVMEEWKQCCPEFGYNLEGTRIGALAYADDLVLLA PSRFELEEKLNGLTSALAAAGMELNSAKSAVMIVEKSGKHKTLAIVPGSLQVGSEAIKCLGP TDAVKYLGLRF 258 (65) R20piVivl 5'UTR GGGAGCCATGGTTGCATGGTCTGTTTACCTCCTCGTGGTTCCCGCCGGGGTCAGAAGGGTGA GCCCTGAAAAGCGGTGATCCCTTCTCAGCCAAATTTCAGACCACCCGTCAGGGGCCGACCAC CCCTGTCGGGGTTATCCACTTGGTTACGCTACCTTCAATCGATGAAAAATCCTCCGGTACAT CAACGAGTGCCGGTTACCAAGTGGAGGATCTTCACAGCCGGACTGATCCACCGGTGAGGTTA GAG 259 (65) R20piVivl 3'UTR TAACCGGTCCTGAAAGACCCCTGTCTGGTCGGTGGATGAACGCTGCGCGTGCGCTCCCTTCT TCTCTCTATCCTCATGCAGGAGATCTTTCCGACCTATGACGGTGGACCGCGGAAACCGAAAG GACGCGATTCCCTGATGGCTGGT^AGACCCTCTGCGCT^AGCCTGTTGGCCATGGATCT^ATGTC AATTTVAAGACATTGATTCAAAATATGTTGTTATC 260 (66) R20piViv2 ORF MKSFDPFSAKLQTTRQGPTTLVGFFHLVTKPPKSGKSSGTSTSTGTQVEDLHSRTDPPVSVE NRVHVEVGNWCDICGLSYRTARGLGQHKRHRHPIELNDERLRLLPRRKGEWSDFESEKLVQ LADEMASTIPKKSELYAALAAKFAGRSAEAIKKRLIKMQWSGITKYKNGAERRPNPLPKTPE CERTTDDEEVTDGRLAENSDCANWRNSMLVCIADGARQAGQQPEARALGEIAERMLSGKLNV VQARERLTSWERMFPEVWTPHKGAMRKAIPKSKKAQRRVTYARLQSLYKRKRKEAAKCVLN GQWKELWKCVEAKPKGTMEYWKGVLGAEAHLDARPVPTTVQEWSILSPITSAEVTGALKESV GSSPGMDKKDARELLTWNPSVLAQLLNLFLVTELPPKTLSRARISLIPKTVSPMSPGDYRPI AISSVVLRLLHKLLFRRWRRVVKLENIQFAFQERDGCLEASSLLNAILHSVHDTVRPIAAAF LDISKAFDRVSQDTILRVAQAHGAPMPLVRYLRCLYSDGWNLNGEDVKSKRGVRQGDPLSP LLFMMVMDEVVKQCRPELGYNLGSARVGALAYADDLVLLAPSRSELEEKLKGLAPALAAAGM DLNGAKSAAMIVEKSGKHKTLAIVPGSLQVGSAEIECLGPTDTVKYLGLRFNWKGRVRTNAG NIFQEMLSNISRAPLKPYQKLEILKEFATPRLQYELVLGSAHRNTLKALDVAARHAVRAWLR LPKDTPLGFFYAKVKEGGLGLTSFATTIPLLQRKKFQRIASSPDPWRGLLKAKNWTEQRL AYIPVRAKETLVSSADEASQAWRADLKSSVDGRELATDSVDCASFDWLANPGTVLPRLFIRG IQLRAGVLGSKVRNARGRSVASDELLCRGRCGVAETLSHILQRCQVTHDARCARHNRLVQNL AGRLSRRGYQVMTEPIIPVGRTFCKPDLVIRHEENAYVLDVTVARGQRLAESWALKTAKYGL 261 KEVETYIQSNLFGRPLGDVRHLPWFTDRGLLCKRSGRGLRSLGLTTKELSVLCLLAIRGSL TCYDVYMRGT (66) R20piViv2 RT RARISLTPKTVSPMSPGDYRPIAISSVVLRLLHKLLFRRWRRVVKLENTQFAFQERDGCLEA SSLLNAILHSVHDTVRPIAAAFLDISKAFDRVSQDTILRVAQAHGAPMPLVRYLRCLYSDGV VNLNGEDVKSKRGVRQGDPLSPLLFMMVMDEWKQCRPELGYNLGSARVGALAYADDLVLLA PSRSELEEKLKGLAPALAAAGMDLNGAKSAAMIVEKSGKHKTLAIVPGSLQVGSAEIECLGP TDTVKYLGLRF 262 (66) R20piViv2 5'UTR CCGGGAGCCATGGTTGCATGGTCTGTTTACCTCCTCGTGGTTCCCGCCGGGGTCAGAAGGGT GAGCC 263 (66) R20piViv2 3'UTR TAACCGGTCCTGTAGGACACCTCTAGGGTCCTTATCTGTTTTTCAGATCCTGCCGGTTGGTT GATATTTTATCGTTTTTGACGAACGGATACTGCGTGTGCTCTCCCTTTTTTCTCTATCCTCA CGCAGGAGATCTTTCCGACCAATGACGGTGGACCGCGGAAACCGGATGGACGCGATTCCCTG ATGGCTGGGAAGAACCTCTGTGCAAGCCTAATGGCTCTGAATCGATGTCAACGACGCCTGAC CTTAGTATGGATCTTTCAAGCTGGAACTATTATTCAACCCGAATGCTTACTTTGAATGTGGC TTGACCGGTCGATTTTGCGACCATGTGAATGACTGAAACAAGTGGAGCCTCCTTTCTTTCCC GAATGCTTCTTGGCGTACTGAATGCTGGACGTGCTAAGAACGAGCCTGCTGGAGGCTTTCGT GCGACAGGAGGAACGACAGACTGTGTTTCCATGGGAGGTCTGAGATATGGCCCTGTTGCGGC GGAGCTGGAGTGCTCAACACGGGGAAGGGCTGCACAGGCGGATTCCTATCCGCCACGACGGC CTAAGGGGGTCCAGAAAATAGGGACCTACCTCCAGGTGTGATTAGACGCCTGGAAAAACTTT C C C AAAAAGGGGAGAC CAATTCCGATGGTGTTACACTGTC GAAGC C C GT GAGC AC GC AAAT T CCATGCCTGCTAATCCATGGGTCCAGACACTTGGACCAACCTTGGTTCACGGGAAGTCGGGA GAACTGTCCATGGACTGCCGAAGGCGTTTTATGAACGAATGGAACTTCAAACTCCCCACATA TACGCACGTCCCCCCCCCTCTTTAATAAAGAGTTGACGCTTGTAAAAGACATTGATTCAAAA TATATTGTTATC 264 (67) R20piViv3 ORF MVMKPISDITPGTTTSAGHQVEDLHSRTDPPVSTELGLHDSNRGVRRWCDLCGLSYKSARG LGQHKRHRHPIALNEERLKLLPRRRGEWSEFESAKLVQLADELASSIPKKAELYAALAAKFA GRSAEAVKKRLIKMQWYGISKYRAKAEQRPELLPKTPGCESTTDDEGVADGRFVENVDYVNW RRSMLECIADGVRQAKKQPDAQALSDIAKGMLSGKLDVDQARIHLTSWDQMFPTVWAPHRG VRRKGIPKSNKAQRKVTYARLQSLYKRKKKEAAKCVLDGQWKELWKCVEAKPEGMMDYWKGV LGAEAHLDARPAPTTAQEWSILSPITSAEVTGALRESVGSSPGMDKKDARELLTWNPSVLAQ LLNLCLVTELPPKTLSRARISLTPKTVSPASPGDYRPIAISSVVLRLLHKLLFRRWRKVVKL EGIQFAFQERDGCLEASSLLNAILHSVHETVRPIAVAFLDISKAFDRVSHDTILRVAQAHGA PMPLVHYLRRLYSDGIVNLNGEDIRSKRGVRQGDPLSPLLFMMVMEEWKQCRPELGYDLEG TRVGALAYADDLVLLAPSRLELEEKLDRLASALTAAGMELNGAKSAVMIVERSGKHKTLAIV PGSLQVGSEWKCLGPTDTVKYLGLRFNWKGRLKTNIGRVFQDMLVNISKAPLKPHQRLEVL KEFATSRLQYELVLGSAHRNTLKALDVAARHAVRAWLRLPKDTPLGFFYAKVKDGGLGLTSF ATAIPLLQRKKFQRLASSPDLWRGLLKAKNVLSEQRLAYVPVRVKETLVSSADEVSQAWRG VLKSSVDGRELVTESVDHASFAWLRNPETVLPRLFIRGIQLRAGVLGSKVRNARGRSGASDD LLCRGRCGMAETLGHILQRCQITHDARCARHNRLVHNLAGRLSRRGYEVMTEPIIPVGGTFC KPDLVVRHGEQAYVIDVTVARGQRLAESWSLKTEKYGLREVETFIRSNLFGRPLGDVKHLPV VFTDRGLLSERSGKGLRSLGLSTKELSILCLLVVRGSLACYDVYMRGT 265 (67) R20piViv3 RT RARISLIPKTVSPASPGDYRPIAISSVVLRLLHKLLFRRWRKVVKLEGIQFAFQERDGCLEA SSLLNAILHSVHETVRPIAVAFLDISKAFDRVSHDTILRVAQAHGAPMPLVHYLRRLYSDGI VNLNGEDIRSKRGVRQGDPLSPLLFMMVMEEWKQCRPELGYDLEGTRVGALAYADDLVLLA PSRLELEEKLDRLASALTAAGMELNGAKSAVMIVERSGKHKTLAIVPGSLQVGSEWKCLGP TDTVKYLGLRF 266 (67) R20piViv3 5'UTR CCGGGGGGCATGGTTACATGGTCTGAATACCTCCTCGTGGTTCCCGCCGGGGTCAGAAGGGT GAGCCCTGAAAAGCGTTGATCCCTTCTCAGCTAAACTTCAGACCACCCGTCAGGGGCCGACC ACCCTTGTCGGGATTTCCAC 267 (67) R20piViv3 3'UTR TGATCGGACCTATAAGACCCTTTAGGTTATTTTCTTGAGTGTTATTTGGTTGTTTATGTTGG TTTTATTGGTAGACAGATACTGCGCGTGGTCTCTCTTCTCTGTGCTCATGCAGGTGATCGCT CCGACCTATGACGGTGGGCCGCGGAAACCGAATGGACGTGGTTCCCTGATGGCTGGAAGAAC CTCTATGCAAGCCGTACGGCCCTGGACCAATGTCAACGATGCTGGCTCTTTGTCTGGATCTT ATATGACGGATTTCCTACTTGACCTGGATGCTTTCCACCTTTTGGCTGTTCTTGCGATCCGA AGGCTGGACGTGCAAAGGACGAGTTCGCCGGAGGCGCTCGTGTGACAGGGGGAACGACGGAC TGTGTTTCCTCGGGAGGTCTGAGGTATGGCCCTGATAATGCGGAGCTGGAGTGCTTAACACG GGAAAAGGCTGCATAGGCGGATTCCTATCTGCCACGATGGCCAAGGGGGGTCCCCAAATAAG GACCTACCTTCAGGTGTGATTAGACACCTGACCAAATTTCCCTGAAAAGGGGATAATTCCGA CGGTGTCTACTGTCGAAGCCCGTAAGCACGCGAATTCCATGCCTGCTGTTAGACGGGTTCAG ACCCTTGGACCAACCTTGGTTCACGGGAAGTTGGGAGAACTGTCCACGGACTGCCGAAGGCC TTGGAGAACGGACGGAACTCTGCTATATTCCAATACACACGCACGTCCCCCCCCTCTTTATT AAGAGT T GAAGAT T GT ACT GAC AT T GAT C C AAAAT AAAT T GT T AAC 268 (68) R2CalDaul ORF LGSTAPWGVFSLVTDTYNKSPLGSSLPGHHQSDLGPAAPVEWSFECSQPLKRASSSSPELL RPVGKRARTTGNSEGTTSGHVVERRMVQSTIGWGERVNANGGVKRVRRPEPETQGASAGEVS NSQWDDNTEGLELIMVEMVEKVEKVRPSCLKKVVAGPSNRRVRFEGVRSVDLDETPEERRAR GATLRPGSKKVLEHGEGGEPVDPSQYQQASGGEVRAFPCQFCALS FTTKAGLGQHMRQRHPL ELNAERLRLISKRPQWNDADDAMLIDKANSLYKSFDTKLAMCKFLKQVFKGRSVEAIKLRLK TLKWSKPTRAIVGGESVPSQSQPSIPSSTSLESGLTVTKSDERANWFVEFAKSLATRMGLAL ERCRDDEVDRLQGRALLDIAEKIRDGQNSLNTARKRISEHAARCFPHTRQPTDERKYGRSSV PSSNRKLKRANYAAIQALYAKSKKDAAEVVLSGKWPVAYKGRQKPPPGHLRYWNKLFSQEGV TDSRPWERSNTSWALVDPITVNELNTALKGLGLASAAGLDRLTVGQVRSMNRNLLVEYLNL LLLTEAAPSQLSKARVTLVPKPGEGGEPVDPSGYRPIAVTSVLLRVLHKILAQRWTKSLLLT SFQVGFLPRDGCLEANLLLQTALRLSHERKIPLAAAFIDVSKAFDTVSHDSLLRAAQSFGAP PPLLNYLRALYTRSEVTVDGRRSVKCQRGVRQGDPLSPLLFIMVMEEVMEQSLPSLGVKLPN FNAHAVAYADDLVVFSSNGDCLLERLNHLEAALARSGMSLNTKKSRTLVIAACGKSKVTALL PTEFRVKDGQLRPIGVNDKVRYLGLEFTWKGQEKVKHTTKLEGFLQNLTKAPLKPAQRMELL RDFAIPSLLYELVLGDAHLNTLKKLDRMVRSKIRTWLRMPKDVPTAFIHANVWDGGLNVERL SVTVPLMRRKRLEKVLTRDTNVTTVVRTCSAFQNKLRQAARPVKVNGEVVMNRREYQGATKQ ALLSTLDGKELGMPDVDPESFRWQDPSNIFPRLYIRGLQLRAGVLATKVRRGRGMRSGNRP TIAAREFLCRGGCGYPESLVHILQKCQVTHEARCARHNRWRFLSAKFKRAGYEVLVEPIIP VTGSFRKPDLVVKLGNKAYVIDVSWSGHSFDPSWGIKVRHYNTYDVHAGLYALFGNEIVLK HVP FL IS YRGLVCKRS TAPWRMNVLTGRDIRDL S LLAVRGS LKAYDVYMRGT 269 (68) R2CalDaul RT KARVTLVPKPGEGGEPVDPSGYRPIAVTSVLLRVLHKILAQRWTKSLLLTSFQVGFLPRDGC LEANLLLQTALRLSHERKIPLAAAFIDVSKAFDTVSHDSLLRAAQSFGAPPPLLNYLRALYT RSEVTVDGRRSVKCQRGVRQGDPLSPLLFIMVMEEVMEQSLPSLGVKLPNFNAHAVAYADDL VVFSSNGDCLLERLNHLEAALARSGMSLNTKKSRTLVIAACGKSKVTALLPTEFRVKDGQLR PIGVNDKVRYLGLEF 270 (68) R2CalDaul 5'UTR TGTCTGGCTATTCTAGGATGGCCAGAGGAGCTTTCGGGTTCCAGCCTTATGTGGGCCTTTCG GGGCTCTGCTTAGTGCTCTACACGCACCATGTGGCGTGCTTTGCAGACTCATAGTTACGGAA ATACCAGGGCCCCCTATTGGCCCCGCCGGGTCAGCTGTCTCTTCCTTCGGGTAAATGACAGT GAGCTAACGCTGGTACGGTTTCCATCTTCGGATGCGCGGTTCAGTCCCGTGTTGAAAAGCTA AATACTGAACTGGGGGAGCCTGCCATCACATCCCTCGTAAGCTGGATTGGTATCCGCGTTGC CCGATTTCGGTCGGGGATCCAGCGCCCTCTGGCAACGGAGGGTAATCGGCATACCAGGCGTG GGAGTAGGCATGTCCCGTATATATATGGGCCTGCTTGCTGAGGATTCCTAACCTGCCCTAGC TTCTGCTTGGGTGGGGACCGAGTCCTGAGGTTGGCTACGTTGGGAGGGTTCGCTCCTTCCCC CCGTCCATGAGCCCTGATGGGATTTCCCAAAAGGGTGAGGCCGACCGACCGATTCGTCGGTC TATCTGTCACAGAGGGCGCCTAGTTCGGGTGAGCTCTAGGGGTGACAGGGGGCCCCGGTGGG GCTCAATTGCTTCTCGCAAAACCTCTTTCCCACTGTTCTTTGTTTCTGCTTTCTCTTACATG ATCTTGCTCCGGGTCTCGTACTTGATCGGGCTAGTCGGTGCTGGCCTTAAAACGGTGGCAAA CTCCCTCCC 271 (68) R2CalDaul 3'UTR TAGGACGTCTGGAGGAACGCGAGGACTGGTACGAAACGAGGATTGACAGTGTTGGACGTTGG CACGACCCAAAGGACCAATCGAGACCGCGGGATGACCTGGGCTGCCTGAAAGCCCATCAGGG AAGGGTAGTCTGCGATGACGAGTCAATGGAACTTGATCGCTCTAACACCCATGTCGGGGTGC CCACTCAGTGTCGAATTGTACGGGATGAATTGGTGCTAACAATTTGAAGACGGAATTTCATT GGACGTGCATACAATGATTGATTTTATGAACTGACAGTTTGACTTCTTATGAAAGAACATTA TGTGCCTCTGCTACTCTGTTACTTTCACAAAATTTTTCTTATCCTTGTATTTATTTTATGAA C T C C GC C C GT AC GAT AC GT AC T GAAAAT AAAC GAT AAAGG 272 (69) R2CalDau2 ORF MHSDPLSSPSGSPDAKRPRVEGPEVWEEGFDIEAIERALEGTVSTPQGVSEVGELAVVQLPG ESPQVERTVETGSCNLNAGDGAVEGQPQAVSLSNCTICHAVFHTARGVAQHMRFKHPEMHTH PKAITTVRGQQSSGGETCPCTHCNAVFITARGLGQHMRQRHPFELNEARRKLSVNRRFWTPQ DDAALLEHANKQCRNFATRMALCKCLCQLFTGRTREAIDLRLKTLRWSKPICPVGRDCHVIP QAESQSTMAGEMVREEAYDQWFSESAS GLVERLSRAAKGDDAKVDQTQGHTLLDTAEKLKAG TTSIKGARKRMQQHATLCFPHKRRPTKVMEPSQTKAQVSKRKQRRANYAAIQALYAMSQKDA AETVLSGGWKDAYKGRARVPREHFDFWAKLFEGKAVADQRPVSQKVETNWDLIRPITSEEVS QALRELRNTATGLDRVSVSEVNSINRGMLVEYLNLLLLTEAAPGQLSKARVTLVPKTAEALE PGDYRPIAVTSILLRALHKILARRWSNVLKLDSLQVGFQPRDGCMEANLVLQTALRLSHEKT TPLAAAFVDVAKAFDTVSHETIIRAAISYGAPSPLVNYLRALYSRSEVTLDGKRTIVCNRGV RQGDPLSPLLFIMVMEEVLELALPRARFQVCDFSAHALAYADDLVVFANNADRLREKLVALE QALSLAGMAVNAGKSHTLTIDCNTKLKQCTLLPTSYTIHGEALRPLGVNDRVKYLGLWFTWK SRERVKHTGKLEDLLQNISRAPLKPQQRVCMLRDYALPRLQYELILGDAHSNTLKRMDLMVR RNVKAWLRFPRDTPSPLFYVGIGHGGLGIPQLSAMIPLQRRERLQKVLARDTAINVMIRPLG AFKAKLKVANRNVMVEKQAVTSKSEYHRAMETCLFGKVDCRELGVPDVDPDSFRWIRDPRGV FPRLYIRGLQLRAGVLGTKVRRARQKGIRSLARTMQYDTTIRCRGGCGQPESIGHILQNCSV THEARCARHNRIVHSVAKRLRQSKYQVTVEPIIPVTGSFRKPDIVAVKDGIAHVIDIAVVTG IGFEYPWRLKVEKYS TLEVHAGIKS LFGSNVQILHS PLLVTNRGLIYRRSAAMLRSMGLSGR 273 DIGDICLLAIRGSLKEYDVYMKGT (69) R2CalDau2 RT RVTLVPKTAEALEPGDYRPIAVTSILLRALHKILARRWSNVLKLDSLQVGFQPRDGCMEML VLQTALRLSHEKTTPLAAAFVDVAKAFDTVSHETTIRAATSYGAPSPLVNYLRALYSRSEVT LDGKRTIVCNRGVRQGDPLSPLLFIMVMEEVLELALPRARFQVCDFSAHALAYADDLWFAN NADRLREKLVALEQALSLAGMAVNAGKSHTLTIDCNTKLKQCTLLPTSYTIHGEALRPLGVN DRVKYLGLWF 274 (69) R2CalDau2 5'UTR TACCTGGCCACCTTTGGGTGGTCAGAGGGGCCTTCGGGTTCCAGCCTTATGTGGACCTTTCG GGGTCCTGCCAGATTCCGTTTGCACTTACACTGCACTCGAGCTGGTAGACTTATAGTTACAG AAATACCAGGGCCTGCTATCGGCCTAGTTGGGTAAGCCACCTTCTTTTATGAGAGATTGGTG GTGAGCTAACACTGGTACGGGTTGCTTCCTTCGGGTGGCTGGTTCAATCCCGTGTTGAAAAA CTAAATTTGAACCGGGAGGGTCACCATGCCCTCTCTGAGTCGATCTTGGTGCGTGCGTTGCC CGACTGCTGTCGGGGGATCGGCGCCTGTCCTCTGGATGGGTAATCAGCCCACTTGCACGGGG GTGAGCATTTCCTGGTAGGTCTGCTCACTGTGGGACTCAGACCTTGCGCACCTTGGTGTGTG AGGTTTGGGTTCCACTGGTCGGCTACGCAGCGGAGGCCTTGGCTTCTGATCGTCCGTGGGCC TGATCTTGTGAACATTTTCAGGTGAGGCCGACTGGCAGACGCCCAAAAAGTCTGTCTCACTG CTACTGGAGACTCCTAGGAGGTGTAAGCATAGGAGTGGCAGCACTGCCCTCGGGTAGTTATA GTCTCCAAAATGCGGTCGGATGGCCACTCTTCGGTGGGGCCAGGCGCGCACCAGGTCTCGTA CCCCGGCCGGGGCTGGGTAACCAGCCCAAATTGGTGGCGTGCTAGGGCATATGGGTCAACAC CCCGTAGGCCTGAAATAGTTGAATCGTGCCAGTCTCTCAAATTAAAATACAGTTCCCTGCTA AGGCACGGGAACAGCACGTAAATGGGCTGTGCAGGAAGCCGCCCGTGGTAGTTGTGAGCTCT GGT GC C AAT C T C C AGGGAGAC AC AGGA 275 (69) R2CalDau2 3'UTR TGATGGAACAAACGCGCAACCGGGCCATTGGGGCTATTCTGGACTCTTAGACGACCGGCAGA TACCGGCGGGACAATTGGCATCGTGCAGGTCCGACCATGGGATTCGTACCACCTCCAACTAT ACACACCGATGAATGGGTTATGCTGAAAGCTCATCCAGAGAAGGTATAGCGCTGATTCAGGT GACCTGCATGGCCCATAGCGCTTCGGCGCCCCTCACTGCTGGCTTGGACAGCCTGACTGGTT CGTACGCATGAAGGATCTATCTGGACTGGAACATCACAACGATTGCATTTAGACACTAAGTC AC GGAAC GC C T C TAT C T CAT GGT CATT C T GC GC GT AT AAAAAT T C AAAC AAGAC AAAAAAC C CAACCAGCTGGATTCCTTACATATTCAAAGACCAACCTTGGAGGTCGCGCGCCCGAGCGGAT GGTTCATGTCTAAGGAACGGCACGCAATTACTTGATAACAAACACTTTGTGCGGAATGACTG TACCAACTCGTTATCTTGCATTTTCCTCTTATTTTATTATATTTTATAAGTAACACTTGCTG TCATAAGCCGCTTTGAAAATATATGTTACA 276 (70) R2SchJap ORF MSAMLNTTTECHPVSTGVNADPSFSYSSTCLCCFSSFASNSLLLDHATASHSANIVCPPSES GSFQLVCMLCSSHYLSSRGFTQHLRHVHPDAYNSLKCLRLNASPLTHRSWSSEEDVCLLSRA DELSASCRLKVDLYNRLHTVFPSRSPEAIKKRLRFLSSSSESSSSAPSPSDISSAASSVSSL PVDLDAPTRSLIPTRRPARSHSSSILSFFTRTPRDVSSSASPVVLHSSPSTTIVINNASVRL HLDSPVSSHALESSCMSSLATNPLHIIDNQHLAASPPLSGVHCPSVPSSAPAAAHVDQSFDN PALGSTPVDSCPPVTSLTLLPAQLSDVAVNLMTSCPELIKPASPSPPLMDDNLLQLILPSDS SNMSPHTVPPPDVWAPMCTDSTRELISAALRLITQNSPLMHAPTLREFLQAALVNMPDMIE IQLFLNSHAELQFPTKWRPSKPRLPPTYRANTSRKHLRRLQYGHIQTLYNRCRRDAANTVLD GRWRSPHTSSPFSIPEFETFWKTIFTTPSTPDNRPWPVLPMCPALLDPITPDEITWALKDM RNSAPGVDRLSAQHFLNFDVPSLAGYLNMVLAFKFLPTNLSISRVTFIPKGASPQQPNDFRP ISIAPVITRCLHKILAKRWMPLFPSSKLQFAFLQRDGCFEAINLLHSLLRHAHERHSGCSIA LLDISRAFDSVSHHSILRAAHRFGAPDGLCQYLQRVYNGASSLFNTVDCAPSRGVKQGDPLS PLLFTMSLDEALESIETDSPVTVDGLPISYTAYADDLVTLAPNADLLQKKLDKLASLLQRSG LIINTSKSMSIDLIAGGHSKLTALKPTVFKIDGNQLQRLNVSDHFDFLGISFDYKGRSKMDH VETLSAYLLNLTQAPLKPQQRISILRENLEPRLLYPLTIGVVHKCTLRQMDRLIRSSVRKWL RLPSDTPTSFFHSSISTGGLGIPHLSSIIPLHRRKRAAKLLLSPCPIIRWVSQSPSFSNFLR ICNLPINVHRDLIHSFDEARCSWSKQLHSTCDGRGLSMSSRNTVSHLWLRYPEHIFPRLYIN AIKLRGGLLSTKVRRSRGRQENADLLCRGRCGHHESIQHILQHCSLTHDIRCRRHNDICRLV ASRLRRNNIRFFQEPCIPTPDSFCKPDFTITRDSTAYVLDVSVCDDANVHLSRQLKTNKYGC STVVSSIYNFLNATGLRISSVRQTPLIITYRGLIDPLSTTSLRRLSFSSRDISDLCVASIQG SMRIYNTYMRGTSPQDP Til (70) R2SchJap RT ISRVTFIPKGASPQQPNDFRPISIAPVITRCLHKILAKRWMPLFPSSKLQFAFLQRDGCFEA INLLHSLLRHAHERHSGCS IALLDISRAFDSVSHHSILRAAHRFGAPDGLCQYLQRVYNGAS SLFNTVDCAPSRGVKQGDPLSPLLFIMSLDEALESIETDSPVIVDGLPISYIAYADDLVILA PNADLLQKKLDKLASLLQRSGLIINTSKSMSIDLIAGGHSKLTALKPTVFKIDGNQLQRLNV SDHFDFLGISF nz (70) R2SchJap 5'UTR C GAAT T T T GC T GC GT GAGAGC T T AGAAAT AT T T T C T T C GC T AT AC T T C AGT TT T T CAAAGC G GAGATAGCCAAATTATCGATTACTTCACTACGTGGGACGTGCACTATCTCTGGATATCATTT ACTTTGCTTTCCACACACATTTAGCTGTTTCGTCATCATGACCACCAACTCGACATTCGTCG CTTCTATATTCAGCATCTTTCGGGTTCTGAATCACCCTGCAGTTTTGTCTGTTCGTTATTCA CTATTCTGTGAAGTCATGGTGAGGGCCTTTTCTGGTCTGTGACGCGGGCAACTTAACCTGTT GCTCGTCCTCATCTGCACGACTGATCCTATGTGATCTACTCCTGC 279 (70) R2SchJap 3'UTR TGATTCGAGCATTCCATATATATTATATTACATTATGCGTCGCAGGCTCATACTGCATCTGC TCTATCAAGCACCTATTGAATTTATATGACAGACAATATTTCTCTTATGTGTTATTTGAAAT TTGTTAACTTTAAAATTATTTGCATTTCAAATAATCTTTCTCTAAACACAATTAACATTGCA AAC AC C C AT T T GGGAT T GT AT AT GC TAT T GAT GT T TAAAAATAAATAT GT T AC 280 (71) R2SchSol ORF LQTCAGSPGVSDPEVHSNDPGPSAVGERPVSTGLFASRLPPCPGCDRILRSAAGLKLHVRSA HPELLSQINQSDVTRSAAILRTTNVSDWQCQYCVRQFQTARGCSMHTKSAHSDEYHRSRVP LASGRRVWTPQEDNLLCSRAAALLVDGLLSLRELARKLQGAFPGRSAEAIYKRLSKLEKDEL LSRNLVTVIPTPVVGSPPNSASNPPTNQPEEEESTPDYRSQLLRTAATQLEASPCQALVTEE IVSIAIDLLMGEIGIADAQQKMEAHAKKVFPHRWRPGVNRRPKMERPCTRRQLRKAQYAEVQ ARLAKRPKLAAQFVLSGDWRSASSEEPPRPAGTLDYWKAISETPSGKDQRPVPSVVKHWSLI DPILSTDVTRELRRMRGSAAGVDGLNVSEVSTWPPAAIAGYLNVILAVGQLPGQHCVSRTTL IPKVPIPQTPSQYRPISVSNVLPRLLNRVLALRWSRCCPSARFQFGFQERDGTAEATGLLHG MLRYAVTAPKSVAVAVLDVSKAFDSVNHETILRAATSGGAPAPLLSFLESTYSRQKTCISDT AVKCLRGVRQGDPLSPLLFSLALSEALTHSNRQLGMDIANTTVDSIAYADDLVLFAETPFRL QERLNGLVTGLSKAGMVLNPAKCLSFYTQALGKAKSSCLSPCSVCIGGEPLRVLGPTDAFTY LGVPFTYRGKQPIRHRPLLYKMLTEISQAPLKPPQRITLLKRHCVPKIMHDLVLGSVYRQTL KRLDIQIRQAVRAWLRLPTDTPTSFFYASLRDGGIGLPCLLTSVPLMKRKRLDAQLSSTEEA VRVAS APPEAL TALQQASRPVLIHQAVINSKEDAKKMWREQLYRSVDGRPLAHIGTSASVHH WLSSPDRLFPWLYLRGIQLRAGVLSTKARRSRRKRLSDVLCHGRCGQIETLPHILQCCQVTK EARIWRHNS IMKSITAKMRRGKADVLLEPHVPEGS S YCKPDWVCMKGS IQVMDVAVAGEMN MDRVYTGKVNRYCTEEVANNLRAIFRKPSDYPVLHKPVIFSSRGGLLRKSELNLKSVGLTDF DVS DLCVLAIRGS LKAYDVYTRGSNDRRGRQAPAVRS NRML 281 (71) R2Sch$ol RT QYRPISVSNVLPRLLNRVLALRWSRCCPSARFQFGFQERDGTAEATGLLHGMLRYAVTAPKS VAVAVLDVSKAFDSVNHETILRAATSGGAPAPLLSFLESTYSRQKTCISDTAVKCLRGVRQG DPLSPLLFSLALSEALTHSNRQLGMDIANTTVDSIAYADDLVLFAETPFRLQERLNGLVTGL SKAGMVLNPAKCLSFYIQALGKAKSSCLSPCSVCIGGEPLRVLGPTDAFTYLGVPF 282 (71) R2SchSol 5'UTR ACTGACGAATTCTCTTGTGTGCTCTTCTGTGAAAAATGTGTTCGCCAATGTTCTGCTGCCCA CCTGCGCTCTGGGTGCTCCGGGGTCGTCGCCGGTCCGTCTTCGGGCCGTTCTACGCCTTCCT CGGTGAGTCATAGTGATGGCACGTTACCTCCGCGTGGTACTCCTGGGGAGGCGGATGGACCC TCTCATACTGATGTGGACTCCGTCTTC 283 (71) R2SchSol 3'UTR TAACTCTGACGTGAAATGTATGATATCTGTACTGACATTATGGAACATACCCCTTTGTCTTG TACTCTTGCACATTATGCATAACATTGATGAGTTCTGCCCAACTGTCTTGACAGTGGGTATA ATAAATACTTCC 284 (72) R2SpiEri ORF MMSSNEVSPPASAGVSATSGLICVHCGRAYRSAAGLKCHLRRCQPESVLSPSVSVPAEPSPR NFVCDHCGRGFSSQRGRSLHVKSAHPAAYFAERSRLAPSRTTWTTQEDALFRRCASAVLQAS GPLALRALAREVGIQFPTRSVEAVFKRLSKLDKDEPLFTPPVSLSAVGPSSSSPSPAPPAVC EPDQVEFYRTSLLHSAVKLLTDSPCQALASGDLLSVASDLLMGEAQLSDSAARLDAHAAWF PRRWRPGVNRRPTWARPTASHKLRRAQYAEVQARLAKNAKAGAQFILSGNWRNAPCPEAPL PPGTLEFWRELTERPSEPDQRPIQPPTAVAWEILEPITATDVTGNLRLMQGSAAGIDGLSAK DLLKWSPSAIAGYLNIILAIGHLPAQHCTCRTTLVPKVSTPTLPSEYRPIAVSNIIPRLLTR ILAHRWSRLCPTARFQFGFQERDGTAEATSLLHGMLRYAVSAPRSIAVAVLDVAKAFDSVNH GTLLRAAEANGAPPLLTTLLASTYSRATTYILDAEVRCQRGVRQGDPLSPLLFNCALSEALS YSDRQLGFDLAGVTVDSIAYADDLVLFAESPHRLQQRLDGLANGLSLAGMVLNSAKCLSFYV QALGKEKSACLCPCDVSIGGSVLRSLGPTDTFKYLGVPFSYRGKVTVGHRSALSGMLEELTR APLKPQQRITLLKRHCVPKLLHKLVLGAVHRNTLKRLDVQVRQSVRRWLKLPADTPTSFLHA PIVDGGLGIPCLSVLVPFAKRRRLDSVLSSAEPWRAAATMPSAISGLRLAAQPVRMGHTVL ASKDDARNYWRNELYNSADGRPLAQFAKSACASHWLSSPARVFPWLYLRGIQLRAGVLSTKS RRSRGAGITDVLCRGQCGQRETLFHILQCCQVTHRARVWRHNLAMKLLASKLIARGHEVLVE PHIPEGQTFKKPDIVVCADDRLTWDVAVADEDLMDTVYAGKTRHYSTVEVEGNLRRILGKP ADFPVSHAPAIFSSRGALSPRSEASLKLLGLSKFDLSDLCLAVIRGSLKAYDVYVRGAGNGE NQ 285 (72) R2SpiEri RT TCRTTLVPKVSTPTLPSEYRPIAVSNIIPRLLTRILAHRWSRLCPTARFQFGFQERDGTAEA TSLLHGMLRYAVSAPRSIAVAVLDVAKAFDSVNHGTLLRAAEANGAPPLLTTLLASTYSRAT TYILDAEVRCQRGVRQGDPLS PLLFNCALSEALS YSDRQLGFDLAGVTVDS IAYADDLVLFA ESPHRLQQRLDGLANGLSLAGMVLNSAKCLSFYVQALGKEKSACLCPCDVSIGGSVLRSLGP TDTFKYLGVPF 286 (72) R2SpiEri 5'UTR CTGGGGCCTTGCACCGTCTTGGTCCCGAAGGGTTAGAGTCTTGGCCCCACTTATTGGGTCAG GGGTGCTGCCCTGGAGCATAGTTGGTACGCCTTGCCTTGTCGTGGCACTCCCCTTGACGGGT AGGGTCCACTCGTGGGCCCGATGGCTCAGCCGTACCCGGACTAATTGGCGGCCCCACTGGTC TTGCCGGTGGTTAAACTAGCAATTCCTACCA 287 (72) R2SpiEri 3'UTR TGAGGTTGCAGTGTGGACCCCCGGTCGTTGTATGACGCAGGGTTACTAAACCGACTAGCAGC ACCCCAGTTTAGCTGGCCCTGAGTGGTTCAGCGGCTGAGGACCGTTTGTCTGAGGAGGTACC TTGCTGATGTGCACCGGTGGAGATTGCTGGATGTTGCCCTTCTCCTTCCCCCTGGGATTACG 288 GACTGTTGTTCTGTATCAGCCCCCATGACTGCAAACTGGAATGTGTCCTTACTGTTGTTGCA AATGCTTGCTTACCCTGGGGCATGCTCTGCCCAAATTGTACTTTCAGTTCGGGTATAATAAA TATTATC (73) R2DipCan ORF MVTITDTNDTTEASASANIPGPTGAWLLCPVCSRPYKSRSGLSNHLRSHATVGEGHACQIC AASFRSASGLTQHMRHRHPTVANQVKLERLAAKRTYWRKTDTELLEHLLQRLPCELSPETIV ENIRESFPGKTTRQLTIRVRNLLTHSQPRPVERSGATPSPPCLSAEPPWREALLQATTSLLS ERADDFPGAPELLVTLDRLLSSDADGAREALEIHANTYFGRKWQPTERRSIPVGGFTSRHAL RRAQYAHMQRLYHLRRRDAAETILSGAWETAHVSGQGIPPNSENHWSDVLSLPAVSDTRPIQ KLQPTDWSLLRPIQPQEVKAALTQMKGSAAGPDRISVESVLSWHEGYFTGYLNLLLASSYLP RVLRSSRVTLVPKTPHRPSSPTDLRPISVSSWTRCLHKILAARWSDSITLPALQFAFQKCD GTFEATNLLDGLLRERASHNRDLALASVDVSRAFDSVARDTIFRAASSFGAPAPLLEFIKCG YSEAQAFLGPRCLTPQRGVRQGDPLSPLLFIMAVDEAVRAASPELGASLNGATVDAIAYADD LILLAPTPEQLSHKLTQLRSALRAGGMTVNERKSFILTIRGDTKSKQSAWPFPSVLAHGEP FRSLGPEDSFEYLGVNFSWRGRAPTNHLERLSVWLEHLTRAPLKPQQRVSLLRTSLIPRLHH SLVLGVAHRMTLKAMDRQVRQALRSWLRLPKDTATAFFHADVKDGGLGTPSLSSTIPIHKRK RLDRLLGSANPILQQLARSPVMARAIGQHSHPGLAMGRVVDSLQSSREAWRDLLWETKDGSY LSGIQSSRESSRWLDHPEKTFPRVYIRGVQLRANTLGTKVRSSRGRPIPAELLKCRGQCGAH ESLNHIVQGCAVTHEARCKRHNRVAGLLQTRLERPGRWLGEPRVPLVHSFCKPDLVVLEND TAIVMDVAITSEQRMATAWREKEEKYGEESVARSILQHVRAMGYEASRIEQAPMIISMRGYW YRHSSDKARRLGITKLTRSDLSLLALTGTLRCYDVYMRGTGRARGSRME 289 (73) R2DipCan RT SSRVTLVPKTPHRPSSPTDLRPISVSSWTRCLHKILAARWSDSITLPALQFAFQKCDGTFE ATNLLDGLLRERASHNRDLALASVDVSRAFDSVARDTIFRAASSFGAPAPLLEFIKCGYSEA QAFLGPRCLTPQRGVRQGDPLSPLLFIMAVDEAVRAASPELGASLNGATVDAIAYADDLILL APTPEQLSHKLTQLRSALRAGGMTVNERKSFILTIRGDTKSKQSAWPFPSVLAHGEPFRSL GPEDSFEYLGVNF 290 (73) R2DipCan 5'UTR GGGGTCATGGTTACAGACCTGGGCTCCTCCTCGTGGTTCCCGCCGGGGTCGGACGGCTGGGT CTTGGGATCGGGAGTGGGATCTCCTGGTCCTGGTCCTGGTCCCCTGGCCTGGTCCTCCCAGC TAATGCCCGGGTCACCCCTCTGGAGAATACGGGCTAACCACCCACTCCAGAGGTATCA 291 (73) R2DipCan 3'UTR TAGGTCCCGAATGACGGAGCTTTTTCCCGATAACCAAACCCGTAGTCGACGCACCCCCTCTT GGACTGGTATCTCCATTGCAGTGTACATCCCTTGTTTTCCGCGTGCTTATATGTGTAACTAT GACCCCCCCCTTGCTGTACACAAATGCTGTCCAAAAATAAATGTGTC 292 (74) R2MicRuf ORF LLVPIKKYRDKPGPSGTQADSRDSKVEGAVAGPSGKDSDQVEFRCVCGRVFPSKRSLAMHRH HRHPQELNDERLATLPTKRLVWSKEDDNALIRYANNLWTPGLLKKDLCSKLVEHFPGRSVES VKKRLQLLKWAPPPNSPPTSQDSGLSLSPSGLSPVSVDLTSSWRDSILEAVISNLQEPKLGA EDLVKIANDLRSGMISPTQCAQLLDDHAKRYFPHLWKPTKRKPQRHHGLLSNKKIRRANYAA IQRLYKIQKKDAAKCVLSGQWRKAYLGRANLIEGLDDYWSKIFETASAPDSRDFGPPAEPKW SIIAAITADEVTTALRDMGKSATGLDRISATELLWHQPSLAAYFNLLLVAELAPPHLSKSR VVYIPKTNDPVSPSDFRPISIASVILRAFHKVIAHRITNQLDFSPLQHAFLQRDGCLEASSL LQAVLRKVHDDWPASMLFLDVSKAFDSISHYTLLTVIEASGLPPPLTKYLRHLYDHAFVQL ESRSVKCGQGVRQGDPLSPLLFILALEALLKDSIPEVGFDLDGPTIGYLAYADDLVLLAEKP NRLQEKLDGLVSSLAAAGLSLNAKKSIGLSIAKDGKKKNLVLLPKTYRSGDDIIKPMNINDS VRYLGLDFWKGKITPKHTTKLQKMLEEVSMAPLKPYQRLELLKTFLVPKFTHELVLGSAHR NTLKKLDVLVRDHVRRWLRLPKDTPLGYLHANIKDGGIGIPCFSSSIPILQKDRFTKLMNNQ GPVLDAIKQQKTFSKMMKRINLPCRVNGTAVTSKVQVREAWAAALKDSIDGKELMVPDVDPA SHKWLKTPENIFPRLHLRGIQLRGGLLPTKARNGRGLNRTDINRICNGACNKPETLNHILQI CEITHDARCARHNRIVQKLEQFIRKRNMRTWIEPIIPTSNTFMKPDLLVETNNKLMVMDVSV VAGYRMTETWDLKKQKYGSPTNMDALQSWSESQTSIEQLPIVLSSRGLLFGPSGRGLRSIGL SERDLMDLCLLAVAGSLKCYDLYTRGTKSSQRSMSRKPVTSSL 293 (74) R2MicRuf RT KSRWYIPKTNDPVSPSDFRPISIASVILRAFHKVLAHRITNQLDFSPLQHAFLQRDGCLEA SSLLQAVLRKVHDDVVPASMLFLDVSKAFDSISHYTLLTVIEASGLPPPLTKYLRHLYDHAF VQLESRSVKCGQGVRQGDPLSPLLFILALEALLKDSIPEVGFDLDGPTIGYLAYADDLVLLA EKPNRLQEKLDGLVSSLAAAGLSLNAKKSIGLSIAKDGKKKNLVLLPKTYRSGDDIIKPMNI NDSVRYLGLDF 294 (74) R2MicRuf 5'UTR AGGGCATAGTTGCACGGCCTGGGCGCCTCCTCGTGGCGACCGCTGGATAGGACATGGCTTCA TGCCATGTCTGAACTAAGATCCAGGCCAACCTCTGACTGGGCTAACCACCCGGTCGGAGGCT TACT 295 (74) R2MicRuf 3'UTR TGACCTGCCTTCCCGGTGGCGATGCCTGAGACCTAGCTGTCACTAGCGGTTACGCCTCAAGG ACTCCTGATTGTCTTTCTTCCCCCATCTATCCTTTTATAACTATTGTTTTCTTCTCCCTATG GGCCTGCGTTGGCCACTCTGTAATCGGGATGTTCTTGATAATAAATGATACC 296 (75) R2Chabot ORF MASGGANEFRCDCGTLWPSARSLAMHNFHRHTEKVMAERREKQPAKRLRWSAEEEAALHRQA DRLWSEGMLSKDLCLLLTDFFPGRSAEAIKKRLQSTRWIPPGQRPPVSPEGNEESSLAEQFD FAMWSKDLLEEAVGNLQEPRMGAELLSRIARGLLTGEFSKEEGVKRLEDHACQWFPYRWKSS VPRKSGNPQMHSNKKIRRMNYAAIQRMYHRRLKDAATCVLSGQWRTAYQPRPEVEGLNEYWT 297 KIFETRSVEDTGCLRTPTRTLYSLIGRIIPSEVTAALKTMRSSAPGLDRITASELLAWHQPS IASYYNLLLVLEVCPRYLSCSRVAFLPKVPVPSAPDDLRPISITSVLLRAFHKILARRLNDE LHLTSLQFAFLQRDGCLDATTLLHSILRNIHHTRSPGAMLFLDISKAFDTVSHSTIARIITS AGFPIPLIHYICNLYSNSTVQLGEKMIKCGRGVRQGDPLSPLLFILVIEEILLASLPDVGYN FGGQRLGAIAYADDLVLLAEHPQRLQEKFKIFSEALHTTGMVLNPKKSIGLTISRDGKRKAI VWQPHCYNYLGTPIRPLKIDESVKYLGLQFNWKGRINPRHVGKLDEMLGEISAAPLKPYQRI RILTSFLIPKLTHSLVLGLAYRKTLKRADRLVYAAVRSWLRLPKDTALGYFHASVADGGLGI PCLSTTIPLLQRDQFAKLISQTDPLSVIIREQEAFKVVGNIINRPCRINSRWTSKEEARAE WKTSLSQSVDGSELTIPDVDLASHGWLKYPVRVFPRLFLRGIQLRGGVLPTKARSARGNNRV VVDRSCKGLCGTSETLNHVLQSCEITHNARCSRHNKIVQQLEYLLNKIGIKIWVEPIIPSGS SFIKPDLWMKDNQLWVLDVSIVSGMRLRESWNIKIVKYGSTERVNDIVCWFGSPIAVKQLP IIISNRGLCSTFSGSGLRALGLSRRDITDLCLLTVKGSLMCYDLYNRSTRSSGR (75) R2Chabot RT LSCSRVAFLPKVPVPSAPDDLRPISITSVLLRAFHKILARRLNDELHLTSLQFAFLQRDGCL DATTLLHSILRNIHHTRSPGAMLFLDISKAFDTVSHSTIARIITSAGFPIPLIHYICNLYSN STVQLGEKMTKCGRGVRQGDPLSPLLFTLVIEEILLASLPDVGYNFGGQRLGAIAYADDLVL LAEHPQRLQEKFKIFSEALHTTGMVLNPKKSIGLTISRDGKRKAIVWQPHCYNYLGTPIRPL KIDESVKYLGLQF 298 (75) R2Chabot 5'UTR GTTAGGGTTAGGGTTAGGGTTAGGGTTAGGGTTAGGGTTAGGGTTAGGGTTAGGGTTAGGGT TAGGGTTAGGGTTAGGGTTAGGGTTAGGGTTAGGGTTAGGGTTAGGGTTAGGGTTAGGGTTA GGGTTAGGGTTAGGGTTAGGGTTAGGGTTAGGGTTAGGGTTAGGGTTAGGGTTAGGGTTAGG GTTAGGGTTAGGGTTAGGGTTAGGGTTAGGGCGGGAGTAACTATGACTCTCTTAACTTTCTT GTCATAGTTACAGGCCTGGACACCTCCGCGTGGTGCCCGCTGGATAGGGTATGGGATCTTAT ATCCCATGCCTGAACTAAGTTCCAGGCCACCCTCCTCTCGGGAAGACTTAATTACCCGTTAG GAGGTTGCTGCTGTTTTTTTGTTAAATTGATTAATTTATGTCCGGAGCCCTCTGGTTGACCG GTGATACAGCAGGTAAGTGAGGTAAGACAGTTGTCAAGAATCCACA 299 (75) R2Chabot 3'UTR TGATTTTCGATCTGGATTCGATGAACGACGATTGTCTCCTGTTATGATTTGAATTATTTTCT T GGAGAT GT T GT AT T T ATAAAT T T GCT AAAT T AT AAT T GT AT C T T T T T GAACAT AC T C C AAT AATAAATGTAAA 300 (76) R2LiaOli ORF MEAAEFRCACGRVWPSARSLAMHNHHRHPEVVNEARLQARPVSRLHWTGEEEEALRRLADRT WTAGMLKGELCSKLADSFPGRSAEAIKKRLQHIKWAPLSSGAISSEASTPRAALICDGFDSV EWRKKLLGDIVKNLNEPRMGSDTLVAISQRLRTGELSLVAAVECLEDHAKQWFPHKWRPSIP RSQKPTQPHSRKAIRRATYAAVQRLYYRRQKDAASAVLSGQWRDIYRQRKEWGLNRHWAKV FEIPSVADTEPPIMPSNLLCSLLDRIHPSEVTAALGDMTASAPGLDRLTAGELLKWHQPSLS AYFNLLLAVEAPPRHLACSRTAFIPKVADPTSPEEFRPISIASVLLRAFHKILARRLRDHLD LSSLQFAFLLRDGCLEATTLLRSVLRRIHHERTSCAMLFLDISKAFDTVSHGTLSRVMRSAG FPPPLVSYIQHLYECSTVQLGDTMVSCNRGVRQGDPLSPLLFILVIDDILRKSLPEVGYNFG GLRLGAMAYADDIVLLADHPQRLQEKLDVFSQALHAAGMALNAKKSVGLTVVRDGKRKVVAL DPTCYNYRDGPIRSVGLRESVRYLGLQFDWKGQVRFKHTRKIDSMLEETTRAPLKPHQRLRT LSAFLIPKFTHELVLGAAHRKTLLQLDRQVRVAVRSWLHLPKDTPLGFFHASVRDGGIGIPS FSTTIPILQKNRFEKLASQTSQWSVWRDQAAFRVLSNIVNRPCKLNNMAVTTKKESRVEWQ RALSQSVDGNEVAIPGVDPVSHRWLRDPSRVFPRLFLRGIQLRGGVLPTRARSARGINREVT DKRCRGPCQASETINHILQACEITHDARCARHNRVLQRLDQCIRKGGAETWVEPIICSGSSF IKPDLIVSKLDHLWILDVSWAAPRLPVTWDLKVAKYGSAVCARDISTWHASSVPLKHLPVV FSNRGLCYEPSGKGLRALGLSHRDIMDLCLLTIQGSLKCYDLYTRGTRSGFGGTV 301 (76) R2LiaOli RT CSRTAFIPKVADPTSPEEFRPISIASVLLRAFHKILARRLRDHLDLSSLQFAFLLRDGCLEA TTLLRSVLRRIHHERTSCAMLFLDISKAFDTVSHGTLSRVMRSAGFPPPLVSYIQHLYECST VQLGDTMVSCNRGVRQGDPLSPLLFILVIDDILRKSLPEVGYNFGGLRLGAMAYADDIVLLA DHPQRLQEKLDVFSQALHAAGMALNAKKSVGLTWRDGKRKWALDPTCYNYRDGPIRSVGL RESVRYLGLQF 302 (76) R2LiaOIi 5'UTR AGGGCATAGTTGCACGGCCTGGGCGCCTCCACGTGGCGACCGCTGGATAGGGTGCATTTTTA CACCTGAACTAAGATCCAGGCCACCCTCCTTTTGGGCTTGATTTCCCAATAGGAGGTTCTCT GCTGGTTTCCGAACCAATTTGTAATTGTTGTCCTGTGCTCTCTGGTGGCAGGACTTCCAGCA GACATAGTGCCAGTAACTTCCTTGGCCAATTAGCAGTCCACC 303 (76) R2LiaOli 3'UTR TAZ^AGTTTAGTGGGGTGGGTGTGAGATCTGGGTCT^AGGT^ATGTTCCTTTAGT^ACGGCGCTAG T T AAT T AGC GAGT T T T C GC C T T GGAGGAT GAT TAT GC T T GGT T AAC GT C C C CC AAGAT ATT G GTGGGTTCGGAACCTGTTTGATTATCTGTACCAATAATAATAAATGATAAAA 304 (77) R2BotJar ORF MLTRTDDPRPPGHPDPSCPGSCSRDCRESVAESPRHACPCGCEFPTKRGLAMHRFHRHMAEV NAERLATLPTKKLAWTQEEEAGLLRHASQAWKEGMTKTQIFAAVLPHFPGRSMEAIKKRLQS LKWVPPQNTPERNLQPLHATSGNVAPAALPSPDSSVKVDGQGQNTEDPAASWRRALLAAAVD HLEEPKLGAETLRQITQDLENGKISSKKCRVLMNEHAKHWFPHTWKPSSARPEPKARQWSNR EIRRGNYGATQKLYKLRKRDAAQTVLSGRWRTAYRGRAPMPAKMEEYWSEVFQAPSATDAIP PGSPSDTLWSVMGKITSSEVTAALKGMRNSAPGLDRITAEELLTWHQPSLASYYNLMLVAGG PPKHLACSRVTFIQKVELPQTPGDYRPISIASTILRALHKILAWRLRDTLRLSPFQHGFLQR 305 DGCLEATALLHAILRKVHNSRKPCAMLFLDVAKAFDTVSHQTLFRVASEMGLPPPLVNYLKY LYSRSTIKLADKVIKCGRGVRQGDPLSPLLFIMVMEVIVREALPEVGFNLDGQRVDSLAYAD DLVLLAEKSTRLQEKLERLSEALRKAGMALNARKSHGLTVTKASKRKQMVLTPTTYECEGDT IRPMGTDDSVRYLGLHFNWKGRIVPKHTGKLDTLLKELTRAPLKPYQRLELLRFHTVPKLTH ELVLGHAHRNTLKKLDCLTRAAVRQWLRLPQDTPLGYLHAHVKDGGLGIPCFSTSIPLLQQR RFEKIATNPATIFQVLQRQDSFRTQWRRLDKPCRLNSTVVTSKVEVRKEWENMLSNSVDGRE LRYPEVDKASHEWLLRPSRVFPRLHMRGIQLRGGLLPTKARSGRGKNRQVTSKTCRGACQTV ETLNHILQVCEVTHDARCARHNRVLHHLEKLLRKKGIRTTLEPVIPAGSSFIKPDLIIETDT KLFVLDVSVVAGYRMAESWSIKVEKYGRPDRVEAIRRWAAIPEEIRVEHLPVIVSNRGLCYR PSGDGLRALGLTSRDISDLCLLAINGSLRCYDLYMRGTRATRETERHLP (77) R2BotJar RT CSRVTFIQKVELPQTPGDYRPISIASTILRALHKILAWRLRDTLRLSPFQHGFLQRDGCLEA T ALLHAI LRKVHNSRKPCAMLFLDVAKAFDTVSHQTLFRVASEMGLPPPLVNYLKYLYS RS T IKLADKVIKCGRGVRQGDPLSPLLFIMVMEVIVREALPEVGFNLDGQRVDSLAYADDLVLLA EKSTRLQEKLERLSEALRKAGMALNARKSHGLTVTKASKRKQMVLTPTTYECEGDTIRPMGT DDSVRYLGLHF 306 (77) R2BotJar 5'UTR C TAC GGGC C T T AAC TAAGAT C C AAC CC AC C C C T C C GT T AC T GAC AGAC C AC AGT AAC T GAGA TTAAACAGCTGGC 307 (77) R2BotJar 3'UTR TGACAAAGAGGACCCCTCTCTGATTAGGCGGTGACCACCCTGGCCTCTACCGAAA 308 (78) R2BoaFull ORF MDRNTNVKGPHASSPSNAFTCSCGRQFSTKRGLGMHRRHCQPVEVNIERMAVLPTKRLIWSL EEDEALRRCADHQWKTGMLKKDLYTLLLPHFPGRSQEAIKKRLQTIKWVPPTDPALVSHPPP GVDTGSASDRGRDSSAASDSDPDPAATWVSSLLTATTSNLQEAKMGAEELYVIARDLAMGVI SQTQSRALLQDHAQKWFPHLWKPSKPRPLSRTHQWSKRTVRRANYAVIQRLYKLRRRDAAST IFSGQWKNAYRGSPPLPPDMESYWSSVFQTPSAIDDRVPATPSEVYWTLLCAMTPSEVTAAL KSMASSAPGLDRITAATLLTWHQPS IAAYFNLLLAAGGPPEHLACSRWFLPKTEAPSTPGE FRPISIASTILRAFHKILSWRLRDTLQLSPFQHGFLQQDGCLEATTLLHTILRRVHLKCEPC AMLFLDIAKAFDTVSHHTLFRVATAAGLPPPLVCYLRHLYERSTIQLAGTTTVCGRGVRQGD PLSPLLFILVIEDIVTSSLPSIGYDLDGHRIHSIAYADDLVLFAEKSPRLQEKLHLLSEALS KAGMTLNAKKSIGLTIAKDGKRKRTALLPTTYRCGIGNINPLGPGETLRYLGIQFNWKGRVT PKHTGKLETLLQELTQAPLKPQQRLLLLKFFLVPKFTHELVLGHAHRNTLRKMDWLTRAAVR RWLRLPKDTPVGYLHAHIKDGGLGVPCLSTTIPLLQASRLEKIAAHPTTLFQQIQRQDALGP LRRRMNQPCRINTTTVTTKAEAREEWKSTLVASFDGRELGVPKVDPVSHDWLLRPSRVFPRL FLRGIQLRGGVLPTKSRSARGANRKWDKICRGACRATETINHTLQVCEVTHDARCARHNRI VRRLDQLLRRQGIQPSVEPIIPSGTSFIKPDLIAEINNRLWVMDVSWAGHRMQETWKIKVD KYGKPEQVASILRWAAVDSSVPVHHLPIVITNRGLIFEPSAAGLRTLGLSRRDLVDLCLLTI MGS LKCYDVYMRGTF 309 (78) R2BoaFull RT CSRWFLPKTEAPSTPGEFRPISIASTILRAFHKILSWRLRDTLQLSPFQHGFLQQDGCLEA TTLLHTILRRVHLKCEPCAMLFLDIAKAFDTVSHHTLFRVATAAGLPPPLVCYLRHLYERST IQLAGTTTVCGRGVRQGDPLSPLLFILVIEDIVTSSLPSIGYDLDGHRIHSIAYADDLVLFA EKSPRLQEKLHLLSEALSKAGMTLNAKKSIGLTIAKDGKRKRTALLPTTYRCGIGNINPLGP GETLRYLGIQF 310 (78) R2BoaFull 5'UTR TGGTTACGCGGCCTGGACGCCTCCTAGTGGCGACCGCTGGATAAGGGGTAGATAGTTTAACT TCTGCTCCCGAGCTAAGAGCCAGGCCACCCCTCGGCGAGGTTAGTACCTTGTTGAGGTTTCA CTGCTGGTTTTCTAATTGAAAGGAATTGTCCCGGTCCCCCTGGACTTAAGGACTCCAGCAGC 311 (78) R2BoaFull 3'UTR TAAGGTTGAACTGGCTTCTATTGGTCCCCCCCCCAACACATTAGTGTACTACTCAATTAGCG ACTTGTCGCTCTCAGGGAGGCTCTCCTCCCTGATAATATATGTCACG 312 (79) R2BoaFul2 ORF MSSDPPGSMDSSRTEFCTAPKGLESCAGINAYECVCGRRFPTKRGLGMHRRHCQPVEVNQER VAALPTKRQVWSKEEDDALRRHANCQWKKGMLKETLYTSLLPHFPGRSQEALKKRLQSIKWV PTADPKLPSCAPLEVDCSTASGQGREPPATAGVDPSDLWLTCLLEKALSDLREVKMGADELR LIAQNLLKGTVDQLRSRDLLQTHAQKWFPHLWKPSKPHPPPKNNSWSKRSIRRANYAIIQKL YKLRRKDAASTVLSGRWRSAYQGTPPLPSNMEDYWSSIFETPSEIDNKAPAAPLTTHWSLLC PMAPSEVTAALKSMQSSAPGLDRITAQTLLTWHQPSLAAYFNLLLAAGGPPEHLTCSRAVFI PKVDNPSAPGDYRPISIASTILRAFHKIMAWRLRDTLTLSPFQHGFLQQDGCLEATTLLHTI FRRVHLNCNPCAMLFLDIAKAFDTVSHHTLFRVATSAGLPPPLVCYLRQLYDRSTVHLAGKP ITCGRGVRQGDPMSPLLFILVIEDIITHSLPEIGYNIDGQRVHSIAYADDLVLFAEKPPRLQ DKLSLLSEALKNAGMSLNAKKSVAITIAKDGKRKCMALLPTVYRCDTGSINTLGPGDTIRYL GIHFWKGRVTPKHTGKLDPFLQELTQAPLKPHQRLQLLKFFLVPKFTHELVLGHAHRNTLR KMDFLVRAATRRWLRLPKDTPIGYFHARIKDGGLGVPCFSTSIPLLQAARMEKIASHPTTLF QLIQRQDALGPLRRRMSRPCKINSVTVTTKAEVRDEWKHLLVTSNDGKELGIPKTDPSSHDW LLRPSRVFPRLFLRAIQLRGGVLPTKSRSARGNNRQVNDTICRGACKARETLNHTLQVCEKT HDARCARHNRVMRRLDQLLRRQNIHPTVEPIIPSGSSFIKPDLVLDTKDKIWIMDVSIVSGY RTQETWNLKTNKYGLPDRVASILQWMTTKPVPVCHLPIIITNRGLMYEPSATGLRTLGLSR 313 RDIVDLCLLTIVGSLKCYDTYMRGTA (79) R2BoaFul2 RT CSRAVFIPKVDNPSAPGDYRPISIASTILRAFHKIMAWRLRDTLTLSPFQHGFLQQDGCLEA TTLLHTTFRRVHLNCNPCAMLFLDIAKAFDTVSHHTLFRVATSAGLPPPLVCYLRQLYDRST VHLAGKPITCGRGVRQGDPMSPLLFILVIEDIITHSLPEIGYNIDGQRVHSIAYADDLVLFA EKPPRLQDKLSLLSEALKNAGMSLNAKKSVAITIAKDGKRKCMALLPTVYRCDTGSINTLGP GDTIRYLGIHF 314 (79) R2BoaFul2 5'UTR TTGTGACGTGTAGTTACATGGTCTGGGCGCCTCCGAGTGGCGACCGCTGGATAAGGTGTGTG GATTTAATTCCCACACTGAACTAAGATCCAGACCCCCCCCCTACTTGGCCGACCACCTCGTA GCGGGTTTTCTCTGCTGGTTAATTCTGATATATTATA 315 (79) R2BoaFul2 3'UTR TAAGCCGGTACGATTCTAAGACCGAATCCGCCCTAAGCGGTGACAGTTCAGTGCAAACTCTA ATAGCGATTCGTCGCCCTCGGAGGTGTTCTACCTCCGATAATTCATGTTACAA 316 (80) R2TriAlbl ORF MLTLHMDPRPPGSPDPSWPGSCPREVCQESAAEPPKHSCPCGSEFRTKRGLAMHRSHRHQAE VNAERLASLPTRKLVWTQEEEAGLLRHATQAWKKGMAKTQTFASLLPHFPGRSVEATKKRLQ SLKWVPPRDTPERNSQPLNATSGNVAPATLPAPDSSVTIDDQGRVEDPAASWRRALLTAAAV RLSEPKLGAETLRQITQDLQDGKISSKKCRVLMNEHAQHWFPHKWKPTSVRPEPKTRQWSTR EIRRANYASVQKLYKLRKRDAAQTVFSGRWRNAYRGQAPLPAEMDEYWAKIFETPSAIDSVT PEVPSKVLWSVMGKIVPSEVTDALKGMRNSAPGLDRISAEELLTWHQPSLAAYYNLMLAAGG PPEHLACSRVTFIPKLENPQAPGDYRPISIASTILRALHKILAWRLRDTLQLSPFQHGFLQR DGCLEASALLHAILRKVHNSRKSCAMLFLDVAKAFDTVSHQTLFRVASAMGLPPPLVHYLKH LYSRSTVRLANKVTTCGRGVRQGDPLSPLLFIMVMEDIVREALPEVGFNLDGQRVDSLAYAD DLVLLAEKSPRLQEKLHRLAEALRKAGMSLNARKSHGLTVTKVSKRKQMVLSPTSYECEGET IKPMGTDDSVRYLGLHFNWKGRIVPKHTGLWDSLLKELKKAPLKPYQRLQLLRFHAVPKFTH QLVLGHAHRNTLKKLDCLTRAAVRQWLRLPPDTPLGYLHANVKDGGLGIPCFSTSIPLLQQK RFEKIATNPATIFQVIERQDSFRTQRRRLDRPCRLNKTVVTSKAEVREGWGNMLSNSVDGKE LRYPEVDKASHEWLLRPSRVFPRLHLRGTQLRGGLLPTKARSGRGKNRQVTNKTCRGACQNV ETLNHILQVCEVTHDARCARHNRVLHLLEKLIRKKGARATLEPVIPAGSSFIKPDLIIETDT QMFVLDVSVVAGYRMAESWDIKVEKYGRPDRVEAIRRWAAIPEKIRVEQLPVIVSNRGLCYR PSGVGLRALGLTSRDISDLCLLAISGSLRCYDLYMRGTRASKEN 317 (80) R2TriAlbl RT CSRVTFIPKLENPQAPGDYRPISIASTILRALHKILAWRLRDTLQLSPFQHGFLQRDGCLEA SALLHAILRKVHNSRKSCAMLFLDVAKAFDTVSHQTLFRVASAMGLPPPLVHYLKHLYSRST VRLANKVTTCGRGVRQGDPLSPLLFIMVMEDIVREALPEVGFNLDGQRVDSLAYADDLVLLA EKSPRLQEKLHRLAEALRKAGMSLNARKSHGLTVTKVSKRKQMVLSPTSYECEGETIKPMGT DDSVRYLGLHF 318 (80) R2TriAlbl 5'UTR TTACCCATTGGTCTTGATTTTGATACTGGTGTTTTGCGAATTGGTGTTGATTGCAAAGTGTT GTTGCGGTGAATTGACGATTGGTTGCTAGGGTTGGGCACCTCCAAGTGGTACCCGCTGGATA GGGCCTTCGTGCCTGAACTAAGCCCCAACCCACCTCTCCGTTGCTGGCAGACCACAGTAACT GAGAT TAAACAGC T GGT 319 (80) R2TriAlbl 3'UTR TGAGCAGTGCCGAACGGGACCCAGAGGACCGCCTCGCCGATCAGGCGTGGGCGGTGACCACC CTGGCCTCTACCTGAAATAGCGATCTAATCGCCTTAGAAGGCTTGATGCTGGAGGGTCGAGC AGACACCAAGTGTCACGAATGCTCCTTACCCTACCTCTTCTTGCTTCTCTAATAATCAATGT TAACA 320 (81) R2TriAlb2 ORF MVTLHMDPRPPGSPDPSWPGSCPREAFRESAAKLPKHVCPCGSDFKTKRGLAMHRFHRHPAE VNAERLASLPIKKLVWTQEEEGGLLRHANQAWKKGMAKTQIFAAILPHFPGRSVEAIKKRLQ SLKWVPPRDSPEGNSQPLYASSGNIAPTTLPAPDSSVPIDNQGTEADPAASWRKALLTASAG HLSEPKLGAETLRNICQELQDGKISSKKCRVLMNKHARHWFPHTWKPTSARPEPKTRQWSTR EIRRANYAAVQKLFKLRKRDAAQTVFSGSWKNAYRGHAPLPTNMEEYWTEVFGSPSAIDAAT PEVPSKVLWSVMGRIVPSEVTAALKGMRNSAPGLDRISAEELLTWNQPSLAAYYNLMLAAGG PPEHLACSRVTFIPKTDNPQTPGDYRPISIASTILRALHKILAWRLRDTLQLSPFQHGFLQR DGCLEASALLHAILRKVHNNRKSCAMLFLDVAKAFDTVSHETLFRVASGMGLPPPLVHYLKH LYSRSTVRIADKATKCGRGVRQGDPLSPLLFIMVMEDIVREALPEVGFNLDGQRVDSLAYAD DLVLLAEKSPRLQEKLQRLTEALQKAGMSLNARKSHGLTLTKVSKRKQMVITPTAYECDGET IKPMGTDDSVRYLGLHFWKGRIVPKHTGTWDNLLKELKKAPLKPYQRLQLLRFHAVPKFTH HLVLGHAHLNTLKKLDCLTRAAVRQWLRLPPDTPLGYLHANVKDGGLGIPCFSASIPLLQQK RFEKIATNPATIFQILQRQDSFRTQRRRLDKPCRLNTRVVTSKAEVREEWGNMLSNSVDGKE LRCPEIDKASHEWLLRPSRVFPRLHLRGIQLRGGLLPTKARSGRGNNRQVTIKTCRGACQNI ETLNHILQVCEVTHDARCARHNRVLHRLDKLIRKKGARATLEPIIPAGSSFIKPDLIIETDT HLFILDVSVVTGYRMAESWDIKVEKYGRPDRVEAIRRWATIPEKIRVEQLPVIVSNRGLCYR QSGAGLRALGLTSRDISDLCLLAISGSLKCYDLYMRGTRATREN 321 (81) R2TriAlb2 RT CSRVTFIPKTDNPQTPGDYRPISIASTILRALHKILAWRLRDTLQLSPFQHGFLQRDGCLEA SALLHAILRKVHNNRKSCAMLFLDVAKAFDTVSHETLFRVASGMGLPPPLVHYLKHLYSRST VRIADKATKCGRGVRQGDPLSPLLFIMVMEDIVREALPEVGFNLDGQRVDSLAYADDLVLLA EKSPRLQEKLQRLTEALQKAGMSLNARKSHGLTLTKVSKRKQMVITPTAYECDGETIKPMGT 322 DDSVRYLGLHF (81) R2TriAlb2 5'UTR GAATTGTTGATTTTGATACTAGTGGCTTGAGAATTGGTATTGATTGAATAGGTTCATAGATG ATCTGTTGCTAGGGTTGGACACCTCCCCGTGGTACCCGCTGGATAGGGCATTCGTGCCTGAA CCAAGCTCCAACCCACCCCTCTGTTGCTGACAGACCACAGCAACTGAGGTTAAACAGCTGGT 323 (81) R2TriAlb2 3'UTR TGAGCCGTGCCGAACGGAACCCAGAGGACCGTCTCTTGATTAGGCGGTGTCCACCCTGGCTT CTACCTGAATTAGCGAATTTTTATTCGCCTTAGATGGCCTGATATAGGAGGGCTGAGTAGAC ACCGCGTGTCACGAATGCTCTTTACCCTACCTCTTCTCGCCTCTAATAATCAATGTCAACA 324 (82) R2CroTig ORF MLTDTWLRPPGLPDPSCPGSCPRVASPKSDAECPKHSCPCGSEFRTKRGLAMHRFHCHPAE VNAERLTTLPTKKLVWTQEEMDGLLRHANGAWKEGMLKTQIFTSLMPHFPGRSAEAIKKRLQ S L KWV PARD NP E RNS Q P LHAT S GNVAP AT L P T P D P S RVD D Q GAN IE D PAAS WRRAL L T AAAD HFKEPKLGAGTLKQITQDLLNGKISSRECRVLMGEHAQHWFPHTWKPSSARPEPKARQWKAR EIRRANYAAVQKLYKLRRRDAAQAVFSGSWRNAYRGRAPQPDKMDQYWAEVFETASATDVTP PGSPSEIYWSVVSKITPSEVADALKGMRNSAPGLDRITAEELLTWDHPSLAAYYNLMLAAGG PPEHLACSRVTFIPKVENPQTPGDYRPISVASTVLRAFHKILAWRLRDNLQLSPFQHGFLQR DGCLEATALLHTILRKVHNSRKSCAMLFLDVAKAFDTVSHQTLFRVAVELGLPPPLVNYLKC LYSRSTVRLADKATKCGRGVRQGDPLSPLLFIMVMDDIVRKTLPEVGFDLDGQRVDSLAYAD DLVLLAEKSPRLQDKLHLLSEALRKAGMSLNARKSRGLTITKVSKRKQMVITPTTYECEGEP IKPMGTDDSVRYLGLHFNWKGRIVPKHTGKLDSLLKELTKAPLKPYQRLQLLKFHAVPKFTH ELVLGHAHRNTVKKLDCLTRAAVRKWLRLPQDTPLGYLHANVKDGGLGIPCFSTSIPLLQKK RFEKIATNPATIFQIMQRQDSFRTQGRRLDKPCRLNSTWTSKTEVREEWGNMLSNSVDGRE LRHPEVDKASHEWLLRPDRVFPRLHMRGIQLRGGLLPTKARSGRGNNRQVTSKTCRGACQNV ETLNHILQVCDVTHDARCARHNRVLHRLERLLHKKGLRTTLEPVIPAGSSFIKPDLIIETDT QTYVLDVSVVAGYRMTESWDIKVEKYGRPDRVEAIRKWAAIPATKRVEHLPVIVSNRGLCYQ PSGDGLRALGLTSRDISDLCLLAISGSLRCYDLYMRGTRAV 325 (82) R2CroTig RT CSRVTFIPKVENPQTPGDYRPISVASTVLRAFHKILAWRLRDNLQLSPFQHGFLQRDGCLEA TALLHTILRKVHNSRKSCAMLFLDVAKAFDTVSHQTLFRVAVELGLPPPLVNYLKCLYSRST VRLADKATKCGRGVRQGDPLSPLLFIMVMDDIVRKTLPEVGFDLDGQRVDSLAYADDLVLLA EKSPRLQDKLHLLSEALRKAGMSLNARKSRGLTITKVSKRKQMVITPTTYECEGEPIKPMGT DDSVRYLGLHF 326 (82) R2CroTig 5'UTR CGACCATTTGGTGTTGATATTGATACTGGCGACTGGCTAGTTGGTGTTGGTTGAAAGTGCTG GCGAGGTTGAGCTGATAATTGGTTGCACGGGTTGGGCACCTCCTAGTGGTGACCGCTGGATA GGGCTTCGGCCTGAGCCAAGATCCAACCCACCCTCCGTTGCTGGCAGACCCCAGTAACTGAG ATTAAACAGCTGGT 327 (82) R2CroTig 3'UTR TAGGACTACCGAGCGCCACCGGAGGGGACCCAGAGGACCGTCTCGGTGATTAGGCGGTGACC GCCCTGGCCTCTACCTGAAATAGCGATCAAATCGCCTTAGAGGGCCTGATTTGGGGGGTTGG GCAGACACTCTGTGTCATTACTGCCCTTTACCTTTCCACTTCTTGCCTGTCTAATAATAAAT GTTAACA 328 (83) R2CroHel ORF MLTDTWLRPPGLPDPSCPGSCPRVASPKSDAECPKHSCPCGSEFGTKRGLAMHRFHCHPAE VNAERLTTLPTKKLVWTQEEMDGLLRHANGAWKEGMLKTQIFTSLMPHFPGRSAEAIKKRLQ S L KWV PARD NP E RNS Q P LHAT S GNVAPAT L P T P D P S RVD D Q GANIED PAASWRRALLAAAAD HFKEPKLGAGTLKQITQDLLNGKISSGECRVLMGEHAQHWFPHTWKPSSARPEPKARQWKAR EIRRANYAAVQKLYKLRRRDAAQAVFSGSWRNAYRGRAPQPDKMDQYWAEVFETASATDVTP PGSPSETYWSVVSKTTPSEVADALKGMRNSAPGLDRITAEELLTWDHPSLAAYYNLMLAAGG PPEHLACSRVTFIPKVENPQTPGDYRPISVASTVLRAFHKILAWRLRDNLQLSPFQHGFLQR DGCLEATALLHTILRKVHNSRKSCAMLFLDVAKAFDTVSHQTLFRVAVELGLPPPLVNYLKC LYSRSTVRLADKATKCGRGVRQGDPLSPLLFIMVMDDIVRKTLPEVGFDLDGQRVDSLAYAD DLVLLAEKSPRLQDKLHLLSEALRKAGMSLNARKSRGLTITKVSKRKQMVITPTTYECEGEP IKPMGTDDSVRYLGLHFNWKGRIVPKHTGKLDSLLKELTKAPLKPYQRLQLLKFHAVPKFTH ELVLGHAHRNTVKKLDCLTRAAVRKWLRLPQDTPLGYLHANVKDGGLGIPCFSTSIPLLQKK RFEKIATNPATIFQIMQRQDSFRTQGRRLDKPCRLNSTVVTSKTEVREEWGNMLSNSVDGRE LRHPEVDKASHEWLLRPDRVFPRLHMRGIQLRGGLLPTKARSGRGNNRQVTSKTCRGACQNV ETLNHILQVCDVTHDARCARHNRVLHRLERLLHKKGLRTTLEPVIPAGSSFIKPDLIIETDT QTYVLDVSVVAGYRMTESWDIKVEKYGRPDRVEAIRKWAAIPATKRVEHLPVIVSNRGLCYQ PSGDGLRALGLTSRDISDLCLLAISGSLRCYDLYMRGTRAV 329 (83) R2CroHel RT CSRVTFIPKVENPQTPGDYRPISVASTVLRAFHKILAWRLRDNLQLSPFQHGFLQRDGCLEA TALLHTILRKVHNSRKSCAMLFLDVAKAFDTVSHQTLFRVAVELGLPPPLVNYLKCLYSRST VRLADKATKCGRGVRQGDPLSPLLFIMVMDDIVRKTLPEVGFDLDGQRVDSLAYADDLVLLA EKSPRLQDKLHLLSEALRKAGMSLNARKSRGLTITKVSKRKQMVITPTTYECEGEPIKPMGT DDSVRYLGLHF 330 (83) R2CroHel 5'UTR CGACCATTTGGTGTTGATATTGATACTGGCGACTGGCTAGTTGGTGTTGGTTGAAAGCGCTG GCGAGGTTGAGCTGATAATTGGTTGCACGGGTTGGGCACCTCCTAGTGGTGACCGCTGGATA GGGCTTCGGCCTGAGCC7^AGATCCAACCCACCCTCCGTTGCTGGCAGACCCCAGT7\ACTGAG ATTAAACAGCTGGT 331 (83) R2CroHel 3'UTR GACTACCGAGCGCCACCGGAGGGGACCCAGAGGACCGTCTCGGTGATTAGGCGGTGACCGCC CTGGCCTCTACCTGAAATAGCGATCAAATCGCCTTAGAGGGCCTGATTTGGGGGGTTGGGCA GACACTCTGTGTCATTACTGCCCTTTACCTTTCCACTTCTTGCCTGTCTAATAATAAATG 332 (84) R20xyLepl ORF LLTEGRGIVTGLNMHIFFSPGPPGLSDSSDRDGNANSTGTQSEANNPSFPCFCGAQFKTKRG LGKHQSYRHPAQVNAERVKALPTKRLTWSHEDDEALRRLANNIWKDGMMKKVLITNLTPYFP GRSHEAIKKRLQVITWSPERAEHPTVRETPDTNPVERDTPGTTDPVTHGPDPSASWRDALLR AAAEHLTESNMGAEELTQIARDLQNGVSRKRIRTRLNQHAEKYFPHKWKPSVIRPKKTIASS KKAIRRANYATVQKLYKLRQRDAASTVLSGRWRSAYKGPAPIPQGMEEYWRSVFETPSAADN SVPWPSTVLWSLMEPIAPSEVTAALHGMKASAPGLDRISAEELLTWDQPSLAAYYNVLLAV GGPPKHISCSRWFLPKTEDPSAPGDYRPISIASTILRAMHKILAWRLRDTLQLSPLQHAFL QRDGCLEASTLLHTIFRGVHTDRVPCAMLFLDVAKAFDTVSHMSLFRVAREAGLPRPMVSYL RHLYQESTIQLAEATTQCGRGVRQGDPLSPLLFIMVMDDIIKSSLPDIGFDLNGQKIGSLAY ADDLVLLAGNPSRLQEKLNLLSEGLQRAGMALNAKKSHGITIARDGKRKCMALVPEAYKCKG DNIQPLGTDDSVKYLGLQFNWKGRITPKHTGKLATMLNELTKAPLKPHQRLKLLKIHLVPKL THELVLGHAHRNTLKKLDCLTRAAVRRWLRLPPDTPVGYFHANVKDGGLGMPCFSTSIPLLQ QKRLEKIALSPASLFQEVQRQDSFRTLGRRIERPCRLNGLEVATKAEVREGWRIALSSSVDG RELSIPKVDKASHEWLRNPARVFPRLYIRGIQLRCGLLPTKARSARGNNRQVTDRTCRGACR APETLNHVLQVCEVTHDARCARHNRVLRSLEKLLSRAGIQTRVEPIIPSGASFIKPDLIAEM ENQLWVLDVSVVAGYRLEESWEIKSAKYGRPDRVADIRRWAAVPDTTPVFQLPVIISNRGLF YEPSGKKLRALGLSCRDIMDLCVLAIGGSLKCYDWYTRGTKDWKC 333 (84) R20xyLepl RT CSRWFLPKTEDPSAPGDYRPISIASTILRAMHKILAWRLRDTLQLSPLQHAFLQRDGCLEA STLLHTIFRGVHTDRVPCAMLFLDVAKAFDTVSHMSLFRVAREAGLPRPMVSYLRHLYQEST IQLAEATTQCGRGVRQGDPLSPLLFIMVMDDIIKSSLPDIGFDLNGQKIGSLAYADDLVLLA GNPSRLQEKLNLLSEGLQRAGMALNAKKSHGITIARDGKRKCMALVPEAYKCKGDNIQPLGT DDSVKYLGLQF 334 (84) R20xyLepl 5'UTR GAAGATCATAGTTGCATGACTTGGACGCCTCCGCGTGGCGACCGCTGGATATGATACTACGG TAT C AGAAC T AAGAT C C AAGT C AC CCCTCTGCC 335 (84) R20xyLepl 3'UTR TGATTTGCTTTGCTTTGTATTGTCTGTATGACGTTGACGTTGTTGTCTAATAGCGGGCGACC GCCTTGAAAGGGGAGGCGGGCGGGGAAGGTACAAATATATGTATATATGTGTAAGTTTTGAC ATCCCTATACATTGCTGTAACCTGTAACTGTCTTGTTTTGCCTTTTCAAAAATAAAATGTAA C 336 (85) R20xyLep2 ORF LLTEGRGIVTGLNMHIFFSPGPPGLSDSSDRDGNANSTGTQSEANNPSFPCFCGAQFKTKRG LGKHQSYRHPAQVNAERVKALPTKRLTWSHEDDEALRRLANNIWKDGMMKKVLITNLTPYFP GRSHEAIKKRLQVITWSPERAEHPTVRETPDTNPVERDTPGTTDPVTHGPDPSASWRDALLR AAAEHLTESNMGAEELTQIARDLQNGVSRKRIRTRLNQHAEKYFPHKWKPSVIRPKKTIASS KKAIRRANYATVQKLYKLRQRDAASTVLSGRWRSAYKGPAPIPQGMEEYWRSVFETPSAADN SVPWPSTVLWSLMEPIAPSEVTAALHGMKASAPGLDRISAEELLTWDQPSLAAYYNVLLAV GGPPKHISCSRWFLPKTEDPSAPGDYRPISIASTILRAMHKILAWRLRDTLQLSPLQHAFL QRDGCLEASTLLHTIFRGVHTDRVPCAMLFLDVAKAFDTVSHMSLFRVAREAGLPRPMVSYL RHLYQESTIQLAEATTQCGRGVRQGDPLSPLLFIMVMDDIIKSSLPDIGFDLNGQKIGSLAY ADDLVLLAGNPSRLQEKLNLLSEGLQRAGMALNAKKSHGITIARDGKRKCMALVPEAYKCKG DNIQPLGTDDSVKYLGLQFNWKGRITPKHTGKLATMLNELTKAPLKPHQRLKLLKIHLVPKL THELVLGHAHRNTLKKLDCLTRAAVRRWLRLPPDTPVGYFHANVKDGGLGMPCFSTSIPLLQ QKRLEKIALSPASLFQEVQRQDSFRTLGRRIERPCRLNGLEVATKAEVREGWRIALSSSVDG RELSIPKVDKASHEWLRNPARVFPRLYIRGIQLRCGLLPTKARSARGNNRQVTDRTCRGACR APETLNHVLQVCEVTHDARCARHNRVLRSLEKLLSRAGIQTRVEPIIPSGASFIKPDLIAEM ENQLWVLDVSVVAGYRLEESWEIKSAKYGRPDRVADIRRWAAVPDTTPVFQLPVIISNRGLF YEPSGKKLRALGLSCRDIMDLCVLAIGGSLKCYDWYTRGTKDWKC 337 (85) R20xyLep2 RT CSRWFLPKTEDPSAPGDYRPISIASTILRAMHKILAWRLRDTLQLSPLQHAFLQRDGCLEA STLLHTIFRGVHTDRVPCAMLFLDVAKAFDTVSHMSLFRVAREAGLPRPMVSYLRHLYQEST IQLAEATTQCGRGVRQGDPLSPLLFIMVMDDIIKSSLPDIGFDLNGQKIGSLAYADDLVLLA GNPSRLQEKLNLLSEGLQRAGMALNAKKSHGITIARDGKRKCMALVPEAYKCKGDNIQPLGT DDSVKYLGLQF 338 (85) R20xyLep2 5'UTR GAAGATCATAGTTGCATGACTTGGACGCCTCCGCGTGGCGACCGCTGGATATGATACTACGG TAT C AGAAC T AAGAT C C AAGT C AC CCCTCTGCC 339 (85) R20xyLep2 3'UTR TGATTTGCTTTGCTTTGTATTGTCTGTATGACGTTGACGTTGTTGTCTAATAGCGGGCGACC GCCTTGAAAGGGGAGGCGGGCGGGGAAGGTACAAATATATGTATATATGTGTAAGTTTTGAC ATCCCTATACATTGCTGTAACCTGTAACTGTCTTGTTTTGCCTTTTCAAAAATAAAATGTAA C 340 (86) R2AzeFeal ORF LLRTSTVGKLLNMLTRSKDPRPPGSPDLSSTGSCDGVASLESSPEFSRHPCPCGSEFRTKQG LAMHRYHRHPAEVNAERLVSLPTKKLVWTQEEEAALLRHASQAWKKGMMKVELFTCLLPHFQ GRSEEAIKKRLNRLQWVPPVDNPERDVPERNSLPLPIPAVSGHVAPATHPLPEAKMVEDQGR 341 NTGSVESWRRDLLATVADHLSETKLGIEALSQILGGLKSGQISTDKCRALMNDHARQQFPHT WKPSSARPGAEARKWSQREMRRANYATVQKLYKLRRRDAAHTVLSGRWRTAYRGHAPLPSNM EEYWSAIFETPSETDAAIPEVPTEIFWSVMGRIAPSEVTSALKGMRNSAPGLDRISAEELLT WHQPSLAAYYNLMLAAGGPPEHLACSRVAFIPKNDNPQTPGDYRPISIASTILRALHKILAW RLRDTLQLSPFQHGFLQRDGCLEATALLHTILRKVHHNRKPCAMLFLDVAKAFDTVSHQTLF RVAAAMGLPPPLVDYLKNLYSRSTVRIADKATRCGRGVRQGDPLSPLLFIMVMEDIVRRVLP EVGFNLDGQRVDSLAYADDLVLLAEKSSRLQEKLHLLTEALQKAGMALNASKSHGLTLDKVS KRKQMVLTPTTYECKGGTIKPMGTDDSVRYLGLHFNWKGKIVPKHTGKLDSLLKELTKAPLK PHQRLQLLKGHLVPKFIHELVLGHAHRNTLKKLDCLTRAAVRHWLRLPQDTPIGYLHAHVKD GGLGIPCFSTSIPLLQQKRFEKIATNPATIFQIIQRQDSFRTQGRRLDRPCRLNGAVMTSKA EVREEWGNVLSNSVDGKELRCSEVDKASHGWLQHPGRVFPRLHMRGIQLRGGLLSTKARSAR GKDRQVTDKTCRGSCHCPETLNHILQVCEITHDARCARHNRVLHRLEQMLRKKGLRTTLEPV IPSGSSYIKPDLIIETGTRRYWDVSVVAGYRMKESWDIKVEKYGRPDRVNNIRKWAAIPEQ DLVIQLPVIVSNRGLCYRPSGEGLRALGLTCRDISDLCLMSINGSLRCYDLYMRGTRSDKVR GRPRNTEGG (86) R2AzeFeal RT CSRVAFIPKNDNPQTPGDYRPISIASTILRALHKILAWRLRDTLQLSPFQHGFLQRDGCLEA TALLHTILRKVHHNRKPCAMLFLDVAKAFDTVSHQTLFRVAAAMGLPPPLVDYLKNLYSRST VRIADKATRCGRGVRQGDPLSPLLFIMVMEDIVRRVLPEVGFNLDGQRVDSLAYADDLVLLA EKSSRLQEKLHLLTEALQKAGMALNASKSHGLTLDKVSKRKQMVLTPTTYECKGGTIKPMGT DDSVRYLGLHF 342 (86) R2AzeFeal 5'UTR TCGCCCCACAACTTGACCTTGGTTTTGATGTTGAATGTGAATTGTTGCAAAGCGAATTGTTG TGGACGCGAGATTGACGAACAGTTGCACGGGTTGGACACCTCCCAGTGGTGAACGCCGGATA GGGCCTTGTGCCTGAGCTAAGAGCCAACCCAAACCC 343 (86) R2AzeFeal 3'UTR TAGGGGACTCCCACAGGACTGCATAGGCAGTGTCCCCTCCACGCACTATCCTGAAGTAGCGA TGAGTATCGCCTTAGAAGGCCTGATGGGGGAGGCTGAGTGGACACAATGTGTCACAAACGCT CTTTACCTCTCCTCGTCTTGCCTGTCTAATAATATATGTTAACA 344 (87) R2AzeFea2 ORF LLRTSTVGKLLNMLTRSKDPRPPGSPDLSSTGSCDGVASLESSPEFSRHPCPCGSEFRTKQG LAMHRYHRHPAEVNAERLVSLPTKKLVWTQEEEAALLRHASQAWKKGMMKVELFTCLLPHFQ GRSEEAIKKRLNRLQWVPPVDNPERDVPERNSLPLPIPAVSGHVAPATHPLPEAKMVEDQGR NTGSVESWRRDLLATVADHLSETKLGIEALSQILGGLKSGQISTDKCRALMNDHARQQFPHT WKPSSARPGAEARKWSQREMRRANYATVQKLYKLRRRDAAHTVLSGRWRTAYRGHAPLPSNM EEYWSAIFETPSETDAAIPEVPTEIFWSVMGRIAPSEVTSALKGMRNSAPGLDRISAEELLT WHQPSLAAYYNLMLAAGGPPEHLACSRVAFIPKNDNPQTPGDYRPISIASTILRALHKILAW RLRDTLQLSPFQHGFLQRDGCLEATALLHTILRKVHHNRKPCAMLFLDVAKAFDTVSHQTLF RVAAAMGLPPPLVDYLKNLYSRSTVRIADKATRCGRGVRQGDPLSPLLFIMVMEDIVRRVLP EVGFNLDGQRVDSLAYADDLVLLAEKSSRLQEKLHLLTEALQKAGMALNASKSHGLTLDKVS KRKQMVLTPTTYECKGGTIKPMGTDDSVRYLGLHFNWKGKIVPKHTGKLDSLLKELTKAPLK PHQRLQLLKGHLVPKFIHELVLGHAHRNTLKKLDCLTRAAVRHWLRLPQDTPIGYLHAHVKD GGLGIPCFSTSIPLLQQKRFEKIATNPATIFQIIQRQDSFRTQGRRLDRPCRLNGAVMTSKA EVREEWGNVLSNSVDGKELRCSEVDKASHGWLQHPGRVFPRLHMRGIQLRGGLLSTKARSAR GKDRQVTDKTCRGSCHCPETLNHILQVCEITHDARCARHNRVLHRLEQMLRKKGLRTTLEPV IPSGSSYIKPDLIIETGTRRYWDVSVVAGYRMKESWDIKVEKYGRPDRVNNIRKWAAIPEQ DLVIQLPVIVSNRGLCYRPSGEGLRALGLTCRDISDLCLMSINGSLRCYDLYMRGTRSDKVR GRPRNTEGG 345 (87) R2AzeFea2 RT CSRVAFIPKNDNPQTPGDYRPISIASTILRALHKILAWRLRDTLQLSPFQHGFLQRDGCLEA TALLHTILRKVHHNRKPCAMLFLDVAKAFDTVSHQTLFRVAAAMGLPPPLVDYLKNLYSRST VRIADKATRCGRGVRQGDPLSPLLFIMVMEDIVRRVLPEVGFNLDGQRVDSLAYADDLVLLA EKSSRLQEKLHLLTEALQKAGMALNASKSHGLTLDKVSKRKQMVLTPTTYECKGGTIKPMGT DDSVRYLGLHF 346 (87) R2AzeFea2 5'UTR TCGCCCCACAACTTGACCTTGGTTTTGATGTTGAATGTGAATTGTTGCAAAGCGAATTGTTG TGGACGCGAGATTGACGAACAGTTGCACGGGTTGGACACCTCCCAGTGGTGAACGCCGGATA GGGCCTTGTGCCTGAGCTAAGAGCCAACCCAAACCC 347 (87)R2AzeFea2 3'UTR TAGGGGACTCCCACAGGACTGCATAGGCAGTGTCCCCTCCACGCACTATCCTGAAGTAGCGA TGAGTATCGCCTTAGAAGGCCTGATGGGGGAGGCTGAGTGGACACAATGTGTCACAAACGCT CTTTACCTCTCCTCGTCTTGCCTGTCTAATAATATATGTTAACA 348 (88) R2SisCat ORF MLTGTWLRPPGLPDPSCPGSCPRVASPKSDAECPKHSCPCGSEYGTKRGLAMHRFHCHPAE VNAERLATLPTKKLVWTQEEMDGLLRHANGAWKEGMSKTQIFTSLMPHFPGRSAEAIKKRLQ S L KWVAP RANP E RNS Q P LH AT S GNVAP AAL P T P D P S RVD D Q GANME D PAAS WRRAL L AAAAD HLKEPKLGAGTLKQITQDLLNGKISSEECRVLMCEHAQHWFPHTWKPSSARPEPKTRQWKAR EIRRANYAAVQKMYKLRRRDAAQAVFSGRWRNAYRGRAPQPDKMDEYWAEVFETASATDVTP PGSPSDIYWSVVSKITPSEVADALKGMRNSAPGLDRITAEELLTWDHPSLAAYYNLMMAAGG PPEHLACSRVTFIPKVENPQTPGDYRPISVASTVLRAFHKILAWRLRDTLQLSPFQHGFLQR DGCLEATALLHTILRKVHNSRKPCAMLFLDVAKAFDTVSHQTLFRVAVEMGLPPPLVNYLKH 349 LYSQSTVRLADQATKCGRGVRQGDPLSPLLFIMVMDDIVRKTLPEVGFDLDGQRVDSLAYAD DLVLLAEKSPRLQDKLHLLSEALRKAGMSLNARKSRGLTITKVSKRKQMVLTPTTYECEGET IKPMETDDSVRYLGLHFNWKGRIVPKHTGKLDSLLKELTKAPLKPYQRLQLLKFHAVPKYIH ELVLGHAHRNTLKKLDCLTRAAVRQWLRLPKDTPLGYLHANVKDGGLGIPCFSTSIPLLQTK RFEKIATNPATIFQIMQRQDSFRTQGRRLDKPCRLNSTVVTSKTEVREEWGNMLSNSIDGRE LRHPEVDKASHEWLLRPDRVFPRLHMRGIQLRGGVLPTKARSGRGNNRQVTSKTCRGACQNV ETLNHILQVCEVTHDARCARHNRVLHRLERLLHKKGLRTTLEPVIPAGSSFIKPDLIIETDT HTYVLDVSVVAGYRMTESWDIKVEKYGRPDRVEAICKWAAIPATKRVEQLPVIVSNRGLCYQ PSGDGLRALGLTSRDISDLCLLTINGSLRCYDLYMRGTRAV (88) R2SisCat RT CSRVTFIPKVENPQTPGDYRPISVASTVLRAFHKILAWRLRDTLQLSPFQHGFLQRDGCLEA TALLHTILRKVHNSRKPCAMLFLDVAKAFDTVSHQTLFRVAVEMGLPPPLVNYLKHLYSQST VRLADQATKCGRGVRQGDPLSPLLFIMVMDDIVRKTLPEVGFDLDGQRVDSLAYADDLVLLA EKSPRLQDKLHLLSEALRKAGMSLNARKSRGLTITKVSKRKQMVLTPTTYECEGETIKPMET DDSVRYLGLHF 350 (88) R2SisCat 5'UTR CGACCATTTGGTGTTGATTTTGATACTGGCGACTGGCTAGTTGGTATTGGTTGAAAGCGCTG GCGAGGTTGAGCTGATAATTGGTTGCACGGGTTGGGCACCTCCTTGTGGTGACCGCTGGATA GGGCTTCGGCCTGAACCAAGATCCAACCCACCCTCCGTTGCTGGCAGACCCCAGTAACTGAG AT TAAACAGC TGGC 351 (88) R2SisCat 3'UTR TAGGACTACCGAGCGCCACCGGAGGGGACCCAGAGGACCGTCTCGGTGATTAGGCGGTGACC ACCTGGGCTCTACCTGAAATAGCGATCAAATCGCCTTAGAGGGCCTGATTTGGGGGGTTGGG C AGAC AC T C AGT GT C AT AAC T GC C C TT T AC C T T T C C AC T T C T T GC C T GT C T AAT AAT AAAT G TTAACA 352 (89) R2VipLat ORF LDKASGPEPRSNPPSVAETAEAKLLLMFPCIDDPRPPGPPDRSSPGRRSRVACRESDAKDPG HVCPCGSEFQSKQGLAMHRYHRHMAEENAKRLASLPSKRLAWSQEEDRALLRLATAQWTGGM AKVTLFGLLQPQFPGRSVEAIKKRLQGLKWTAPADNPERDPLPVPPSTAQGDVEPATSPAPT ADPRVFDQNTDDPTVSWRRALLTAVEGKLSEPKMGADTLCRTASQLKNGEINGEACRALMNE HAREWFPHTWKPSSVKDQTDTRRWSKRAIRRANYATVQRLFKLRRRDAAHTVLSGRWRNAYR GQAPLPKGMDQYWSKVFEAGSAKDEKAQVVPDKTLWETLAAVTPSEVTSALKGMKASAPGLD RISAEDLLAWNQPSLAAYFNLMLAAGGPPEQLACSRVTFIPKVDEPKTPGDYRPISIASVIL RAFHKILAWRLRDTVQLSPFQHGFLQRDGCLEASALLHTILRKSHRDRKPCALLFLDVAKAF DTVSHQTLFRVATAMGLPPPLVDYLKHLYGRSTVQIAGQNTKCGRGVRQGDPLSPLLFIMVM EDIVRDALPEVGFDLDGQRVDSLAYADDLVLLAEKSSRLQEKLTLLTAALQNAGMELNARKS HGLTIEKASKRKCMVLRDTKYQCKGEGIQPMGTDDSVRYLGLHFNWKGRLVPKHTGKLDSLL KELSAAPLKPFQRLQLLKLHVVPKFVHELVLGHAHRNTLQKLDCLIRAAVRQWLRLPTDTPL GYLHANIKDGGLGIPCFSTSIPLLQQKRFEKIAQNPATIFQIIQRQDSFRTLGRRLDRPCRL QGAVLTSKAEAREEWGNVLSNSVDGRELRYPDVDKASHEWLLRPSRVFPRLHMRGIQLRGGL LPTKARSARGNNRQVQDKTCRGACRQPETLNHILQVCEVTHDGRCARHNRVLHRLAQLLRKK GVRTTLEPVTPSGSSFIKPDLTAETDKQTYVLDVSWAGGRMKTSWDIKDEKYGRPDRVNDT RKWGAIPEASRVCQLPIIISNRGLCYQATGEGLRALGLTTREISDLCLLAISGSLKCYDLYM RGTRGVRGAPEHRYGAPKGPH 353 (89) R2VipLat RT CSRVTFIPKVDEPKTPGDYRPISIASVILRAFHKILAWRLRDTVQLSPFQHGFLQRDGCLEA SALLHTILRKSHRDRKPCALLFLDVAKAFDTVSHQTLFRVATAMGLPPPLVDYLKHLYGRST VQIAGQNTKCGRGVRQGDPLSPLLFIMVMEDIVRDALPEV...
Claims
1. A method for inserting an exogenous sequence to a genomic DNA of a cell, comprising introducing to the cell(a) a polypeptide or a first polynucleotide encoding the polypeptide, wherein the polypeptide comprises(i) a DNA binding domain or a CRISPR Cas protein,(ii) a reverse-transcriptase comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 6, 2, 10, 14, 18, 22, 26, 30, 34, 38, 42, 46, 50, 54, 58, 62, 66, 70, 74, 78, 82, 86, 90, 94, 98, 102, 106, 110, 114, 118, 122, 126, 130, 134, 138, 142, 146, 150, 154, 158, 162, 166, 170, 174,178, 182, 186, 190, 194, 198, 202, 206, 210, 214, 218, 222, 226, 230, 234,238, 242, 246, 250, 254, 258, 262, 266, 270, 274, 278, 282, 286, 290, 294,298, 302, 306, 310, 314, 318, 322, 326, 330, 334, 338, 342, 346, 350, 354,358, 362, 366, 370, 374, 378, 382, 386, 390, 394, 398, 402, 406, 410, 414,418 and 422, or an amino acid sequence having at least 85% sequence identity to any of the amino acid selected from the group, and(iii) an endonuclease or a nickase, and(b) an RNA comprising (i) a template for the exogenous sequence and (ii) a 3’ UTR, or a second polynucleotide encoding the RNA.
2. The method of claim 1, which comprises introducing the first polynucleotide and the second polynucleotide to the cell.
3. The method of claim 2, wherein the first polynucleotide and the second polynucleotide are on a same vector or on separate vectors.
4. The method of any preceding claim, wherein the 3’UTR is an R2 retrotransposon 3’ UTR.
5. The method of claim 4, wherein the 3’UTR comprise a sequence selected from the group consisting of SEQ ID NO: 8, 4, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76,80, 84, 88, 92, 96, 100, 104, 108, 112, 116, 120, 124, 128, 132, 136, 140, 144, 148, 152, 156, 160, 164, 168, 172, 176, 180, 184, 188, 192, 196, 200, 204, 208, 212, 216, 220, 224, 228, 232,236, 240, 244, 248, 252, 256, 260, 264, 268, 272, 276, 280, 284, 288, 292, 296, 300, 304, 308,312, 316, 320, 324, 328, 332, 336, 340, 344, 348, 352, 356, 360, 364, 368, 372, 376, 380, 384,388, 392, 396, 400, 404, 408, 412, 416, 420 and 424.
6. The method of any preceding claim, wherein the reverse-transcriptase comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 6, 2, 10, 14, 18, 22, 26, 30, 34, 38, 42, 46, 50, 54, 58, 62, 66, 70, 74, 78, 82, 86, 90, 94, 98, 102, 106, 110, 114, 118, 122, 126, 130, 134, 138, 142, 146, 150, 154, 158, 162, 166, 170, 174, 178, 182, 186, 190, 194, 198,202, 206, 210, 214, 218, 222, 226, 230, 234, 238, 242, 246, 250, 254, 258, 262, 266, 270, 274,278, 282, 286, 290, 294, 298, 302, 306, 310, 314, 318, 322, 326, 330, 334, 338, 342, 346, 350,354, 358, 362, 366, 370, 374, 378, 382, 386, 390, 394, 398, 402, 406, 410, 414, 418 and 422.
7. The method of any preceding claim, wherein the polypeptide comprises the endonuclease.
8. The method of any one of claims 1-7, wherein the polypeptide comprises the nickase, which optionally is Cas nickase.
9. The method of any preceding claim, wherein the CRISPR Cas protein is selected from the group consisting of Cas9, Cas 12 and Cas 13.
10. The method of any one of claims 1-8, wherein the DNA binding domain is selected from the group consisting of a transcription activator-like effector (TALE) DNA binding domain, a homeodomain protein, a zinc finger, a helix-tum-helix, a leucine zipper, and a DNA-binding domain of a homing endonuclease, a transposon or retro-transposon.
11. The method protein of claim 10, wherein the DNA binding domain is a TALE.
12. The method of claim 10, wherein the homing endonuclease is selected from the group consisting of I-Scel, I-Crel and I-Dmol.
13. The method of claim 10, wherein the retro-transposon is a long interspersed nuclear element (LINE), optionally selected from the group consisting of RI, R2, R4, R5, R6, R7, R8, and R9.
14. The method of any one of claims 1-5, wherein the polypeptide comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 5, 1, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, 53, 57, 61, 65, 69, 73, 77, 81, 85, 89, 93, 97, 101, 105, 109, 113, 117, 121, 125, 129, 133, 137, 141, 145, 149, 153, 157, 161, 165, 169, 173, 177, 181, 185, 189, 193, 197, 201, 205,209, 213, 217, 221, 225, 229, 233, 237, 241, 245, 249, 253, 257, 261, 265, 269, 273, 277, 281,285, 289, 293, 297, 301, 305, 309, 313, 317, 321, 325, 329, 333, 337, 341, 345, 349, 353, 357,361, 365, 369, 373, 377, 381, 385, 389, 393, 397, 401, 405, 409, 413, 417 and 421, or an aminoacid sequence having at least 85% sequence identity to any amino acid sequence selected from the group.
15. The method of claim 14, wherein the polypeptide comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 5, 1, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, 53, 57, 61, 65, 69, 73, 77, 81, 85, 89, 93, 97, 101, 105, 109, 113, 117, 121, 125, 129, 133, 137,141, 145, 149, 153, 157, 161, 165, 169, 173, 177, 181, 185, 189, 193, 197, 201, 205, 209, 213,217, 221, 225, 229, 233, 237, 241, 245, 249, 253, 257, 261, 265, 269, 273, 277, 281, 285, 289,293, 297, 301, 305, 309, 313, 317, 321, 325, 329, 333, 337, 341, 345, 349, 353, 357, 361, 365,369, 373, 377, 381, 385, 389, 393, 397, 401, 405, 409, 413, 417 and 421.
16. The method of any preceding claim, wherein the RNA further comprises a 5’UTR.
17. The method of claim 16, wherein the 5’UTR comprises a sequence selected from the group consisting of SEQ ID NO: 7, 3, 11, 15, 19, 23, 27, 31, 35, 39, 43, 47, 51, 55, 59, 63, 67, 71, 75, 79, 83, 87, 91, 95, 99, 103, 107, 111, 115, 119, 123, 127, 131, 135, 139, 143, 147, 151, 155, 159, 163, 167, 171, 175, 179, 183, 187, 191, 195, 199, 203, 207, 211, 215, 219, 223, 227,231, 235, 239, 243, 247, 251, 255, 259, 263, 267, 271, 275, 279, 283, 287, 291, 295, 299, 303,307, 311, 315, 319, 323, 327, 331, 335, 339, 343, 347, 351, 355, 359, 363, 367, 371, 375, 379,383, 387, 391, 395, 399, 403, 407, 411, 415, 419 and 423.
18. The method of any preceding claim, wherein the cell is a mammalian cell, preferably a human cell.
19. The method of any preceding claim, wherein the exogenous sequence encodes a protein, preferably a therapeutic protein.
20. The method of any preceding claim, wherein the RNA comprises pseudouridine-modified nucleotides.
