Prime editing methods and compositions for the treatment of retinitis pigmentosa

Abstract

The present disclosure provides methods of editing RHO using a prime editor (e.g., for correcting a P23H mutation in a RHO protein) and a pegRNA. Such methods may be useful for treating or preventing retinitis pigmentosa. The present disclosure also provides pegRNAs, ngRNAs, complexes, systems, and compositions for editing RHO and treating or preventing retinitis pigmentosa. Polynucleotides, vectors, cells, and kits for editing RHO and treating or preventing retinitis pigmentosa are also provided herein.

Description

PRIME EDITING METHODS AND COMPOSITIONS FOR THE TREATMENT OF RETINITIS PIGMENTOSARELATED APPLICATIONS

[0001] This application claims priority under 35 U. S. C. § 119(e) to U. S. Provisional Application, U. S. S. N. 63 / 719,236, filed November 12, 2024, which is incorporated herein by reference.REFERENCE TO AN ELECTRONIC SEQUENCE LISTING

[0002] The contents of the electronic sequence listing (B119570202WO00-SEQ-TNG.xml; Size: 1,525,224 bytes; and Date of Creation: October 7, 2025) is incorporated herein by reference.GOVERNMENT SUPPORT

[0003] This invention was made with government support under Grant Nos. HG009490, GM118062, NS132304, and EB031172 awarded by the National Institutes of Health. The government has certain rights in the invention.BACKGROUND OF THE INVENTION

[0004] Prime editing (PE) enables the replacement of targeted DNA nucleotides with any specified replacement of up to hundreds of nucleotides, thereby enabling a wide variety of substitutions, insertions, and deletions in the genomes of living systems. The mechanism of prime editing is inherently resistant both to bystander editing (unwanted editing outcomes at the target site) and to off-target editing. In contrast with nuclease-mediated gene editing, prime editors do not require the creation of double-stranded DNA breaks (DSBs), minimizing undesirable outcomes, such as uncontrolled insertions and deletions (indels), large deletions, p53 activation, retrotransposon insertion, and chromosomal defects. PE does not require codelivery of donor DNA template, is active in mitotic and non-mitotic cells, and has been successfully performed in vivo in mice and in non-human primates.

[0005] Prime editors combine a programmable nickase, such as Streptococcus pyogenes Cas9 (SpCas9) H840A nickase, with a reverse transcriptase (RT), such as an engineered Moloney murine leukemia virus RT. A PE guide RNA (pegRNA) guides the prime editor protein to its spacer- specified genomic target and also contains a 3' extension with a primer binding site (PBS) complementary to the nicked target DNA and an RT template (RTT) encoding the 1 / 235B1195.70202WO00#14468377 v2desired edited sequence (see, e.g., International Patent Application Publication No. WO 2020 / 191239, which is incorporated herein by reference). When bound to its programmed target sequence, the prime editor*pegRNA complex nicks the target site to create an accessible 3' end of ssDNA. This target DNA 3' end hybridizes to the pegRNA’s 3' primer binding site (PBS), creating a primer* tern plate complex that initiates reverse transcription using the RTT to create a 3' DNA flap containing the edited DNA sequence. The 3' flap of edited DNA can displace the original sequence and be ligated into the genome, creating a DNA heteroduplex of edited and unedited DNA strands. This editing intermediate is then resolved into a permanent edit on both strands by DNA repair or replication. A nickase, reverse transcriptase, and pegRNA constitute a “PE2” editing system. A “PE3” system adds an additional nicking guide RNA (ngRNA) that nicks the unedited strand of the DNA heteroduplex intermediate to enhance editing efficiency by directing mismatch repair to remake the unedited strand using the edited strand as a template.SUMMARY OF THE INVENTION

[0006] Prime editing strategies can be developed to correct pathogenic mutations, such as the A: T base pair at nucleotide position 68 in the RHO gene that results in the introduction of a P23H mutation in the RHO protein. This mutation is the most common of many mutations that cause retinitis pigmentosa, a genetic disorder of the eyes that results in loss of vision. Retinitis pigmentosa is the most common inherited retinal dystrophy and a major cause of inherited blindness. It is characterized by the progressive loss of photoreceptors and affects approximately 1 in 4000 people globally. While several treatments for retinitis pigmentosa are available, there is currently no cure. It is uncertain whether gene augmentation (e.g., delivery of RHO transgene that is overexpressed in target photoreceptor cells) is beneficial, and overexpression of dosage-sensitive retina proteins, such as RHO, can cause structural and electrophysiological retinal damage. Nuclease-based strategies utilizing Cas9, Casl3, and other genome editing proteins, as well as epigenetic approaches, have also had limited therapeutic benefit. Moreover, these approaches knock out or knock down RHO, which leads to functional and structural insufficiencies in the retina. The development of a prime editing strategy to precisely correct the RHO gene could therefore offer a much-needed path to a durable, one-time treatment for the common retinitis pigmentosa-causing mutation. The use of a prime editing strategy (rather than another gene editing strategy, such as a base editing2 / 235B1195.70202WO00#14468377 v2strategy) also allows for additional silent mutations to be introduced as described herein, which can help to increase editing efficiency.

[0007] The present disclosure describes the development of a prime editing (PE) approach to correct the RHO mutation that causes the pathogenic P23H mutation in the RHO protein (e.g., in retinal pigment epithelium (RPE) cells). By systematically optimizing prime editing guide RNAs (pegRNAs) and applying several recent advances in PE technology, correction efficiencies of up to 64.4% in RPE cells were achieved.

[0008] Thus, the present disclosure provides pegRNAs for correcting mutations a RHO gene comprising an edit template, a spacer sequence, and / or a primer binding site as disclosed herein. In one aspect, the present disclosure provides pegRNAs for correcting a mutation in a RHO gene comprising an edit template comprising a sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to, or comprising one, two, three, four, or five mutations relative to, the sequence of any one of SEQ ID NOs: 12-184, or the sequence CAGTCCTTT, CTCTCCTTT, or GCAGTCCGT.

[0009] In another aspect, the present disclosure provides pegRNAs for correcting a mutation in a RHO gene comprising a spacer sequence comprising a sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to, or comprising one, two, three, four, or five mutations relative to, the sequence of any one of SEQ ID NOs: 185-284.

[0010] In another aspect, the present disclosure provides pegRNAs for correcting a mutation in a RHO gene comprising a primer binding site (PBS) comprising a sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to, or comprising one, two, three, four, or five mutations relative to, the sequence of any one of SEQ ID NOs: 288-297, or the sequence CGAGTACCC or CGAGTACC.

[0011] In another aspect, the present disclosure provides nicking guide RNAs (ngRNAs) for correcting a mutation in a RHO gene comprising a spacer comprising a sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to, or comprising one, two, three, four, or five mutations relative to, the sequence of any one of SEQ ID NOs: 1257-1275.3 / 235B1195.70202WO00#14468377 v2

[0012] In another aspect, the present disclosure provides methods of prime editing a RHO gene comprising contacting a nucleic acid sequence encoding the RHO gene with a prime editor and any of the pegRNAs disclosed herein.

[0013] In another aspect, the present disclosure provides methods of treating or preventing retinitis pigmentosa in a subject comprising administering to the subject a prime editor and any of the pegRNAs disclosed herein.

[0014] In another aspect, the present disclosure provides systems comprising any of the pegRNAs and / or ngRNAs disclosed herein. In some embodiments, the system comprises a prime editor as disclosed herein.

[0015] In another aspect, the present disclosure provides complexes comprising a prime editor and any of the pegRNAs and / or ngRNAs disclosed herein.

[0016] In another aspect, the present disclosure provides compositions (e.g., pharmaceutical compositions) comprising any of the pegRNAs and / or ngRNAs disclosed herein.

[0017] In another aspect, the present disclosure provides polynucleotides encoding any of the pegRNAs, ngRNAs, systems, and / or compositions disclosed herein.

[0018] In another aspect, the present disclosure provides vectors comprising any of the polynucleotides disclosed herein.

[0019] In another aspect, the present disclosure provides AAVs encoding any of the pegRNAs, prime editors, and optionally ngRNAs disclosed herein.

[0020] In another aspect, the present disclosure provides pharmaceutical compositions comprising any of the pegRNAs, ngRNAs, systems, complexes, compositions, polynucleotides, vectors, and / or AAVs. disclosed herein.

[0021] In another aspect, the present disclosure provides cells comprising any of the pegRNAs, ngRNAs, systems, complexes, compositions, polynucleotides, vectors, and / or AAVs disclosed herein.

[0022] In another aspect, the present disclosure provides kits comprising any of the pegRNAs, ngRNAs, systems, complexes, compositions, polynucleotides, vectors, and / or AAVs disclosed herein.

[0023] In another aspect, the present disclosure provides for the use of any of the pegRNAs, ngRNAs, systems, complexes, compositions, polynucleotides, vectors, AAVs, and pharmaceutical compositions disclosed herein in the manufacture of a medicament for the treatment of retinitis pigmentosa.4 / 235B1195.70202WO00#14468377 v2

[0024] In another aspect, the present disclosure provides for the use of any of the pegRNAs, ngRNAs, systems, complexes, compositions, polynucleotides, vectors, AAVs, and pharmaceutical compositions disclosed herein in medicine.

[0025] In another aspect, the present disclosure provides pegRNAs for introducing a mutation into a RHO gene. In some embodiments, the pegRNA comprises an edit template comprising a sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to, or comprising one, two, three, four, or five mutations relative to, the sequence of SEQ ID NO: 184.

[0026] In another aspect, the present disclosure provides ngRNAs for introducing a mutation into a RHO gene. In some embodiments, the ngRNA comprises a spacer comprising a sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to, or comprising one, two, three, four, or five mutations relative to, the sequence of SEQ ID NO: 1257.

[0027] In another aspect, the present disclosure provides methods of introducing a mutation into a RHO gene in a cell comprising contacting a cell with a prime editor and a pegRNA disclosed herein. In some embodiments, the method further comprises contacting the cell with an ngRNA disclosed herein.

[0028] In another aspect, the present disclosure provides cells produced by a method disclosed herein (e.g., cells to test a method of editing a RHO gene). In some embodiments, the genome of the cell comprises a mutated A: T base pair at nucleotide position 68 in the RHO gene relative to a wild type RHO gene.

[0029] In another aspect, the present disclosure provides methods comprising contacting a cell produced by a method disclosed herein with a prime editor and a pegRNA to correct a mutated A: T base pair at nucleotide position 68 in the RHO gene. In some embodiments, the method further comprises contacting the cell with a ngRNA.

[0030] In another aspect, the present disclosure provides lipid nanoparticles (LNPs) comprising any of the pegRNAs, ngRNAs, systems, complexes, polynucleotides, vectors, and / or compositions disclosed herein.

[0031] The foregoing concepts, and additional concepts discussed below, may be arranged in any suitable combination, as the present disclosure is not limited in this respect. Further, other advantages and novel features of the present disclosure will become apparent from the following detailed description of various non-limiting embodiments when considered in conjunction with the accompanying figures.5 / 235B1195.70202WO00#14468377 v2BRIEF DESCRIPTION OF THE DRAWINGS

[0032] The following drawings form part of the present specification and are included to further demonstrate certain aspects of the present disclosure, which can be better understood by reference to one or more of these drawings in combination with the detailed description of specific embodiments presented herein.

[0033] FIGs. 1A-1C provide background on retinitis pigmentosa (RP).

[0034] FIG. 2 shows the creation of eye-relevant, MMR-proficient retinal pigment epithelium (RPE)- 1 cell lines via PE3max, including the R / / OP23Hcell lines.

[0035] FIG. 3 shows a summary of development of a prime editing (PE) strategy to correct R / / OP23H. Bottom-strand (z.e., non-coding strand) PE approach is shown here. The edit is a +4 T to G (the top, coding strand has the complementary A to C conversion). To increase editing efficiency, PAM- (+6 G> A) and seed-ablating (+2 G> C) MMR-evading silent edits are also included. As shown in the rightmost bar in the graph, the optimized strategy results in 64.4% corrective editing and 8.6% indels in homozygous R / / OP23HRPE-1 cell lines.

[0036] FIGs. 4A-4B show that corrective edits are high fidelity (FIG. 4A), and that indels are deletions (FIG. 4B) for PE6g, pegl538 (20-nt spacer, +1 mismatch G, F+E scaffold [flip: A]) in RtOP23HhTERT-RPEls.

[0037] FIG. 5 shows results of a transgenic R / / OP23Hpig experiment. Three v3em split- AAV strategies were used: PE6e, pegl538, nsg30 (injected); PE6c, pegl538, nsg30; and PE6e, pegl541, nsg30. AAV5 was produced under cGMP standards. Subretinal injections (300 pl, lei 1 vg, contralateral controls).

[0038] FIGs. 6A-6B show PKC alpha stains on bipolar cells in the inner nuclear layer.R / / OP23Hpigs injected at 7 weeks of age (N = 6); contralateral injections: untreated (vehicle control) and treated (PE-AAV) per pair of eyes; sacrificed at 9 weeks of age (N = 3); sacrificed at 11 weeks of age (N = 3).

[0039] FIGs. 7A-7C show results of screening round 1 (PEmax+epegRNAs) using canonical NGG PE2max epegRNA designs to correct R / / OP23H.

[0040] FIGs. 8A-8C show results of screening round 1 (PEmax+epegRNAs) with NRCH PE2max epegRNA designs to correct R / / OP23H.

[0041] FIGs. 9A-9C show results of screening round 2 (PEmax + epegRNAs + nsgRNAs) testing of 19 different nsgRNAs targeting RHO.6 / 235B1195.70202WO00#14468377 v2

[0042] FIG. 10 shows a lack of correlation between PE2 and PE3 editing efficiency in screening round 2 (PEmax + epegRNAs + nsgRNAs). PE3 data shown is for nsg30. Psiope = 0.1530.

[0043] FIGs. 11A-11E depict results of screening round 3 (PE6 prime editors + epegRNAs) showing comparative performance between PEmax and PE6 variants (PE6b (FIG. 11A), PE6c (FIG. 11B), PE6e (FIG. 11C), PE6f (FIG. 11D), and PE6g (FIG. HE) with various epegRNAs.

[0044] FIGs. 12A-12E depict results of screening round 4 (PE6 prime editors + epegRNAs + nsgRNAs) showing comparative performance between PEmax and PE6 variants (PE6b (FIG.12B), PE6e (FIG. 12B), PE6f (FIG. 12C), and PE6g (FIG. 12D)) in combination with epegRNAs on various nsgRNAs.

[0045] FIG. 13 shows the predicted RTT structure for the RHO epegRNAs.

[0046] FIG. 14 shows granular designs for epegRNA screening in screening round 5 (PE6 prime editors + epegRNAs + nsgRNAs).

[0047] FIGs. 15A-15F show results of screening round 5 (PE6 prime editors + epegRNAs + nsgRNAs) for different epegRNA designs.

[0048] FIG. 16 shows results of screening round 6 (all PE6 prime editors + epegRNAs + nsgRNAs) identifying PE6e and PE6g as the best PE6 variant to correct the RHO C.68OA mutation among 15 tested variants.

[0049] FIG. 17 shows 96 possible combinations of edit-proximal silent edits.

[0050] FIG. 18 shows the design strategy for screening mismatch repair (MMR)-evading silent edits.

[0051] FIG. 19 shows that for the +4 T> G correction, +3 G> C and +6 G> A are the best silent edits.

[0052] FIG. 20 shows the optimization of the nucleofection of the prime editing system.

[0053] FIG. 21 shows the optimization of the nucleofection process for RPE-1 cells. +5 edit (+61 nick), BEST1 (c.900G> C); Cells: le5 cells / well, P13, -70-90% confluent (depending on replicate); Plasmids: PEmax (500 ng), epegRNA (165 ng), nsgRNA (55 ng); Recovery: 5-10 min, 37 °C; Centrifugation: 90 ref, 10 min; 16-well strip (4D X Unit).

[0054] FIG. 22 shows the optimization of lipid transfection for RPE-1 cells seeded at 2e3 cells per well.

[0055] FIG. 23 shows the optimization of lipid transfection for RPE-1 cells seeded at 5e3 cells per well.7 / 235B1195.70202WO00#14468377 v2

[0056] FIGs. 24A-24C show the optimization of lipid transfection for RPE- 1 cells seeded at 6e3 cells per well.

[0057] FIG. 25 provides a summary of the lipid transfection optimizations conducted for RPE-1 cells.

[0058] FIGs. 26A-26B show results of screening round 8 (OptiPrime epegRNAs). Results illustrate that the optimized set of MMR-evading silent edits is indeed optimal (+3 G> C, +6 G> A) and the optimized epegRNA designs (PBS, RTT, addition of pegLIT linker) outperform epegRNA designs generated by OptiPrime.

[0059] FIGs. 27A-27G show results of screening round 9 (PBS, RTT, 3' motifs, microhomology of pegLIT linker). FIG. 27B shows that pegLIT linkers have microhomology. FIG. 27C shows the alteration of microhomology in pegLIT linkers. FIG.27D shows comparison of secondary structures of epegRNA 3 ' extensions. FIGs. 27E-27G show (i) that epegRNA design of pegl538, which was used in the pig study and already showed a promising treatment effect in pigs, can be further optimized; (ii) that the new 3 ' motifs improve, in some cases significantly, corrective editing efficiency without significantly increasing indels; and (iii) that slightly increasing microhomology in the pegLIT linker to the pre-PBS DNA sequence can improve, sometimes significantly, corrective editing efficiency without significantly increasing indels.

[0060] FIGs. 28A-28D show results of screening round 10 (3' motifs, pegLIT linker microhomology). FIG. 28A shows epegRNAs tested with six 3' motifs and different pegLIT linkers (with and without additional microhomology). FIG. 28B shows the alteration of microhomology in pegLIT linkers. FIG. 28C shows screening results. FIG. 28D shows the data shown in FIG. 28C with pegRNA numbering.

[0061] FIGs. 29A-29G show a summary of the best epegRNAs for cloning into v3em split-AAV transfer plasmids with nsg30, PE6g. FIG.29A provides schematics of the epegRNAs.FIG. 29B shows that peg2035 leads to high-fidelity edits. FIGs. 29C-29D show additional biological replicates for peg2035. FIG. 29E shows that peg2154 also leads to high-fidelity edits. FIGs. 29F-29G show additional biological replicates for peg2154.

[0062] FIG. 30 shows testing of the optimized PE strategy for correcting R / / OP23Hin vivo in pigs.

[0063] FIG. 31 shows details for biological replicate 1 of the data summarized in FIG. 30. R / / OP23Hcorrection in pigs was performed with high fidelity.8 / 235B1195.70202WO00#14468377 v2

[0064] FIG. 32 shows details for biological replicate 2 of the data summarized in FIG. 30. R / / OP23Hcorrection in pigs was performed with high fidelity.

[0065] FIG. 33 shows details for biological replicate 3 of the data summarized in FIG. 30. R / / OP23Hcorrection in pigs was performed with high fidelity.

[0066] FIG. 34 provides a summary of PE strategies for correcting R / / OP23Husing the three best pegRNAs.

[0067] FIG. 35 shows the genotype distribution for plasmid- treated RPE1 cell lines.Homozygous: n = 495 clones, 79.1% “bulk” corrected alleles. Heterozygous: n = 377 clones, 85.7% “bulk” corrected alleles.

[0068] FIGs. 36A-36C show the assessment of additional pegRNA 3' motifs. RHOP23H / P23HRPE1 cell lines co-transfected with PE6g and nsg30 (+60 nick). All new (e)pegRNAs (pegRNAs, and epegRNAs, which are pegRNAs comprising an additional 3' motif as described further herein) have PBS = 9 nt, RTT = 21 nt, and the same silent edits.

[0069] FIG. 37 shows the comparison of various 3 ' motifs, control motifs, and combinations of motifs. Controls: dead tevopreql, scrambled tevopreql, and no motif had lower editing than new 3 ' motifs.

[0070] FIG. 38 shows the choice of PE system for a pig study. Peg2344 was cloned into AAV transfer plasmid (still with nsg30, PE6g from a previous pig study) with 3 ' motifs (pegLIT linker), peg2154: SBRMVl_UPD_PKb_DOUBLEMUT_hp9A21T_ to_9C21G (‘more microhomology’ pegLIT), peg2306: HAV_PK1, ‘predicted’ pegLIT, peg2344:Hs_SRP, ‘more microhomology’ pegLIT. Edit-to-indel ratios peg2154: 12.0, peg2306: 11.5, peg2344: 16.0.

[0071] FIGs. 39A-39B show the iterative testing of 1051 (e)pegRNAs, 19 nsgRNAs, and 16 PEs.

[0072] FIG. 40 shows macromolecule delivery to the retina by subretinal injection.

[0073] FIG. 41 shows the complexation of RNA with cationic liposomes, as well as the structure of DOTMA, used for lipofection.

[0074] FIG. 42 shows that the retina provides a unique physiological context for delivery. Isolation from significant complex fluids (e.g., blood, serum) results in minimal complex protein adsorption and coagulation. Immune privileged means minimal immune clearance. No direct lymphatics means maximal bioavailability. Accessed via direct injection (300-400 pl) means no limitation via administration dose. Rod and RPE cells adsorb positively charged NPs similarly, implying that RPE1 cells are a good in vitro model for photoreceptor + RPE9 / 235B1195.70202WO00#14468377 v2transfection in vivo. In summary, positively charged NPs retained positive surface charge, have extraordinary bioavailability, and are predominantly limited by cytotoxicity upon subretinal injection and have correlated transfection between RPE-1 cells in vitro and rod, cone, and RPE in vivo. Target cells for treatment of inherited retinal diseases (IRDs):Retinitis pigmentosa: Rods. Cone-rod dystrophy: Cones + rods. Macular dystrophy: RPE (or cones + RPE). Stargardt disease: Cones + rods + RPE. Usher’s syndrome: Cones + rods.

[0075] FIG. 43 shows that fragments of fixed retinal tissues from neonatal and adult rats were incubated with cationic ferritin (CF, black dots, -10-15 nm) and imaged. Normal, adult rat, pH 7.2. CF binding pattern on surface of discarded outer segment packet is similar to that seen on adjacent RPE. Mag. 68,500X.

[0076] FIG. 44 shows the design of LNPs.

[0077] FIG. 45 shows chemical structures of ionizable lipids.

[0078] FIG. 46 shows chemical structures of cationic lipids.

[0079] FIG. 47 shows that addition of naked RNA (no lipids) yields no editing. -15,000 RPE-1 cells / well upon transfection.

[0080] FIGs. 48A-48D show the results of editing and cytotoxicity of PE- LNPs for RHO correction.

[0081] FIGs. 49A-49B show the results of titration of cationic lipid for improved PE-LNPs.FIG. 49B shows the results of using 100 ng of PE-LNPs. PE system includes: PE6g (GenScript), peg2154 (Pixel), nsg30 (Agilent). LNP formulation includes: Ionizable: x%, Cationic: (60 -x)%, DOPE: 10%, Cholesterol: 38.5%, C14-PEG: 1.5%.

[0082] FIG. 50 shows the results of microfluidic-formulated PE-LNPs for R / / O-P23H correction.DEFINITIONS

[0083] Unless defined otherwise, all technical and scientific terms used herein have the meaning commonly understood by a person skilled in the art to which this invention belongs. The following references provide one of skill with a general definition of many of the terms used in this invention: Singleton et al., Dictionary of Microbiology and Molecular Biology (2nd ed. 1994); The Cambridge Dictionary of Science and Technology (Walker ed., 1988); The Glossary of Genetics, 5th Ed., R. Rieger et al. (eds.), Springer Verlag (1991); and Hale & Marham, The Harper Collins Dictionary of Biology (1991). As used herein, the following terms have the meanings ascribed to them unless specified otherwise.10 / 235B1195.70202WO00#14468377 v2AAV

[0084] An “adeno-associated virus” or “AAV” is a virus which infects humans and some other primate species. The wild-type AAV genome is a single- stranded deoxyribonucleic acid (ssDNA), either positive- or negative- sensed. The genome comprises two inverted terminal repeats (ITRs), one at each end of the DNA strand, and two open reading frames (ORFs): rep and cap between the ITRs. The rep ORF comprises four overlapping genes encoding Rep proteins required for the AAV life cycle. The cap ORF comprises overlapping genes encoding capsid proteins: VP1, VP2, and VP3, which interact together to form the viral capsid. VP1, VP2, and VP3 are translated from one mRNA transcript, which can be spliced in two different manners: either a longer or shorter intron can be excised resulting in the formation of two isoforms of mRNAs: a ~2.3 kb- and a ~2.6 kb-long mRNA isoform. The capsid forms a supramolecular assembly of approximately 60 individual capsid protein subunits into a non-enveloped, T-l icosahedral lattice capable of protecting the AAV genome. The mature capsid is composed of VP1, VP2, and VP3 (molecular masses of approximately 87, 73, and 62 kDa, respectively) in a ratio of about 1:1:10.

[0085] AAV particles may comprise a nucleic acid vector (e.g., a recombinant genome), which may comprise at a minimum: (a) one or more heterologous nucleic acid regions comprising a sequence encoding a protein or polypeptide of interest (e.g., a split prime editor) or an RNA of interest (e.g., a pegRNA), or one or more nucleic acid regions comprising a sequence encoding a Rep protein; and (b) one or more regions comprising inverted terminal repeat (ITR) sequences (e.g., wild-type ITR sequences or engineered ITR sequences) flanking the one or more nucleic acid regions (e.g., heterologous nucleic acid regions). In some embodiments, the nucleic acid vector is between 4 kb and 5 kb in size (e.g., 4.2 to 4.7 kb in size). In some embodiments, the nucleic acid vector further comprises a region encoding a Rep protein. In some embodiments, the nucleic acid vector is circular. In some embodiments, the nucleic acid vector is single- stranded. In some embodiments, the nucleic acid vector is double- stranded. In some embodiments, a double- stranded nucleic acid vector may be, for example, a self-complementary vector that contains a region of the nucleic acid vector that is complementary to another region of the nucleic acid vector, initiating the formation of the double-strandedness of the nucleic acid vector.Cas9

[0086] The term “Cas9” or “Cas9 nuclease” refers to an RNA-guided nuclease comprising a Cas9 domain, or a fragment thereof (e.g., a protein comprising an active or inactive DNA11 / 235B1195.70202WO00#14468377 v2cleavage domain of Cas9, and / or the gRNA binding domain of Cas9). A “Cas9 domain,” as used herein, is a protein fragment comprising an active or fully or partly inactive cleavage domain of Cas9 and / or the gRNA binding domain of Cas9. A “Cas9 protein” is a full length Cas9 protein. A Cas9 nuclease is also referred to sometimes as a casnl nuclease or a CRISPR (Clustered Regularly Interspaced Short Palindromic Repeat)-associated nuclease. CRISPR is an adaptive immune system that provides protection against mobile genetic elements (viruses, transposable elements, and conjugative plasmids). CRISPR clusters contain spacers, sequences complementary to antecedent mobile elements, and target invading nucleic acids. CRISPR clusters are transcribed and processed into CRISPR RNA (crRNA). In type II CRISPR systems, correct processing of pre-crRNA requires a trans-encoded small RNA (tracrRNA), endogenous ribonuclease 3 (me), and a Cas9 domain. The tracrRNA serves as a guide for ribonuclease 3-aided processing of pre-crRNA. Subsequently, Cas9 / crRNA / tracrRNA endonucleolytically cleaves a linear or circular dsDNA target complementary to the spacer. The strand in the target DNA not complementary to crRNA is first cut endonucleolytically, then trimmed 3 '-5' exonucleolytically. In nature, DNA-binding and cleavage typically requires protein and both RNAs. However, single guide RNAs (“sgRNA”, or simply “gRNA”) can be engineered so as to incorporate aspects of both the crRNA and tracrRNA into a single RNA species. See, e.g., Jinek M., Chylinski K., Fonfara I., Hauer M., Doudna J. A., Charpentier E., Science 337:816-821(2012), the contents of which are incorporated herein by reference. Cas9 recognizes a short motif in the CRISPR repeat sequences (the PAM or protospacer adjacent motif) to help distinguish self versus non-self. Cas9 nuclease sequences and structures are well known to those of skill in the art (see, e.g., “Complete genome sequence of an Ml strain of Streptococcus pyogenes.” Ferretti et al., J. J., McShan W. M., Ajdic D. J., Savic D. J., Savic G., Lyon K., Primeaux C., Sezate S., Suvorov A. N., Kenton S., Lai H. S., Lin S. P., Qian Y., Jia H. G., Najar F. Z., Ren Q., Zhu H., Song L., White J., Yuan X., Clifton S. W., Roe B. A., McLaughlin R. E., Proc. Natl. Acad. Sci. U. S. A.98:4658-4663(2001); “CRISPR RNA maturation by trans-encoded small RNA and host factor RNase III.” Deltcheva E., Chylinski K., Sharma C. M., Gonzales K., Chao Y., Pirzada Z. A., Eckert M. R., Vogel J., Charpentier E., Nature 471:602-607(2011); and “A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity.” Jinek M., Chylinski K., Fonfara I., Hauer M., Doudna J. A., Charpentier E. Science 337:816-821(2012), the entire contents of each of which are incorporated herein by reference). Cas9 orthologs have been described in various species, including, but not limited to, S. pyogenes12 / 235B1195.70202WO00#14468377 v2and S. thermophilus. Additional suitable Cas9 nucleases and sequences will be apparent to those of skill in the art based on this disclosure, and such Cas9 nucleases and sequences include Cas9 sequences from the organisms and loci disclosed in Chylinski, Rhun, and Charpentier, “The tracrRNA and Cas9 families of type II CRISPR-Cas immunity systems” (2013) RNA Biology 10:5, 726-737; the entire contents of which are incorporated herein by reference. In some embodiments, a Cas9 nuclease comprises one or more mutations that partially impair or inactivate the DNA cleavage domain.

[0087] A nuclease-inactivated Cas9 domain may interchangeably be referred to as a “dCas9” protein (for nuclease-“dead” Cas9). Methods for generating a Cas9 domain (or a fragment thereof) having an inactive DNA cleavage domain are known (see, e.g., Jinek et al., Science.337:816-821(2012); Qi et al., “Repurposing CRISPR as an RNA-Guided Platform for Sequence-Specific Control of Gene Expression” (2013) Cell. 28;152(5): 1173-83, the entire contents of each of which are incorporated herein by reference). For example, the DNA cleavage domain of Cas9 is known to include two subdomains, the HNH nuclease subdomain and the RuvCl subdomain. The HNH subdomain cleaves the strand complementary to the gRNA, whereas the RuvC 1 subdomain cleaves the non-complementary strand. Mutations within these subdomains can silence the nuclease activity of Cas9. For example, the mutations D10A and H840A completely inactivate the nuclease activity of S. pyogenes Cas9 (Jinek et al., Science. 337:816-821(2012); Qi etal., Cell. 28;152(5): 1173-83 (2013)). In some embodiments, a Cas9 protein comprises one or more mutations to inactivate the nuclease activity of only one of the HNH subdomain or the RuvC 1 subdomain.

[0088] In some embodiments, proteins comprising fragments of a Cas9 protein are provided. For example, in some embodiments, a protein comprises one of two Cas9 domains: (1) the gRNA binding domain of Cas9; or (2) the DNA cleavage domain of Cas9. In some embodiments, proteins comprising Cas9, or fragments thereof, are referred to as “Cas9 variants.” A Cas9 variant shares homology to Cas9, or a fragment thereof. For example, a Cas9 variant is at least about 70% identical, at least about 80% identical, at least about 90% identical, at least about 95% identical, at least about 96% identical, at least about 97% identical, at least about 98% identical, at least about 99% identical, at least about 99.5% identical, at least about 99.8% identical, or at least about 99.9% identical to wild type Cas9 (e.g., SpCas9). In some embodiments, the Cas9 variant may have 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 21, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, or more amino acid changes13 / 235B1195.70202WO00#14468377 v2compared to wild type Cas9 (e.g., SpCas9). In some embodiments, the Cas9 variant comprises a fragment of Cas9 e.g., a gRNA binding domain or a DNA-cleavage domain), such that the fragment is at least about 70% identical, at least about 80% identical, at least about 90% identical, at least about 95% identical, at least about 96% identical, at least about 97% identical, at least about 98% identical, at least about 99% identical, at least about 99.5% identical, or at least about 99.9% identical to the corresponding fragment of wild type Cas9 (e.g., SpCas9). In some embodiments, the fragment is at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95% identical, at least 96%, at least 97%, at least 98%, at least 99%, or at least 99.5% of the amino acid length of a corresponding wild type Cas9 (e.g., SpCas9).Fusion protein

[0089] The term “fusion protein” as used herein refers to a hybrid polypeptide that comprises protein domains from at least two different proteins. One protein may be located at the amino-terminal (N-terminal) portion of the fusion protein or at the carboxy-terminal (C-terminal) protein, thus forming an “amino-terminal fusion protein” or a “carboxy-terminal fusion protein,” respectively. A protein may comprise different domains, for example, a Cas9 protein fused to a polymerase such as a reverse transcriptase (i.e., a prime editor). Any of the proteins provided herein may be produced by any method known in the art. For example, the proteins provided herein may be produced via recombinant protein expression and purification, which is especially suited for fusion proteins comprising a peptide linker.Methods for recombinant protein expression and purification are well known, and include those described by Green and Sambrook, Molecular Cloning: A Laboratory Manual (4thed., Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N. Y. (2012)), the entire contents of which is incorporated herein by reference.Guide RNA (“gRNA”)

[0090] As used herein, the term “guide RNA” is a particular type of guide nucleic acid which is commonly associated with a Cas protein (e.g., a Cas9 protein), directing the Cas protein to a specific sequence in a DNA molecule that includes complementarity to the protospacer sequence of the guide RNA. For example, a gRNA may direct a Cas protein (e.g., as part of a prime editor) to a target site in the RHO gene. However, this term also embraces the equivalent guide nucleic acid molecules that associate with Cas protein equivalents, homologs, orthologs, or paralogs, whether naturally occurring or non-naturally occurring14 / 235B1195.70202WO00#14468377 v2(e.g., engineered or recombinant), and which otherwise program the Cas protein equivalent to localize to a specific target nucleotide sequence. The Cas protein equivalents may include other napDNAbps from any type of CRISPR system e.g., type II, V, VI), including Cpfl (a type-V CRISPR-Cas system), C2cl (a type V CRISPR-Cas system), C2c2 (a type VI CRISPR-Cas system), and C2c3 (a type V CRISPR-Cas system). Further Cas-equivalents are described in Makarova et al., “C2c2 is a single-component programmable RNA-guided RNA-targeting CRISPR effector,” Science 2016; 353(6299), which is incorporated herein by reference. Exemplary sequences and structures of guide RNAs are provided herein.

[0091] Functionally, guide RNAs associate with a Cas protein, directing (or programming) the Cas protein to a specific sequence in a DNA molecule that includes a sequence complementary to the protospacer sequence for the guide RNA. A gRNA is a component of the CRISPR / Cas system. The sequence specificity of a Cas DNA-binding protein is determined by gRNAs, which have nucleotide base-pairing complementarity to target DNA sequences. The native gRNA comprises a 20 nucleotide (nt) spacer, which specifies the DNA sequence to be targeted, and is immediately followed by an 80 nt scaffold sequence, which associates the gRNA with the Cas protein. In some embodiments, a spacer of the present disclosure has a length of 15 to 100 nucleotides, or more. For example, a spacer may have a length of 15 to 90, 15 to 85, 15 to 80, 15 to 75, 15 to 70, 15 to 65, 15 to 60, 15 to 55, 15 to 50, 15 to 45, 15 to 40, 15 to 35, 15 to 30, or 15 to 20 nucleotides. In some embodiments, the spacer is 20 nucleotides long. For example, the spacer may be 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, or 25 nucleotides long. At least a portion of the target DNA sequence is complementary to the spacer of the gRNA. For a Cas protein to successfully bind to the DNA target sequence, a region of the target sequence is complementary to the spacer of the gRNA sequence and is immediately followed by the correct protospacer adjacent motif (PAM) sequence. In some embodiments, an spacer is 100% complementary to its target sequence. In some embodiments, the spacer sequence is less than 100% complementary to its target sequence and is, thus, considered to be partially complementary to its target sequence. For example, a targeting sequence may be 99%, 98%, 97%, 96%, 95%, 94%, 93%, 92%, 91%, or 90% complementary to its target sequence. In some embodiments, the spacer of template DNA or target DNA may differ from a complementary region of a gRNA by 1, 2, 3, 4, or 5 nucleotides.

[0092] In some embodiments, the guide RNA is about 15-120 nucleotides long and comprises a sequence of at least 10 contiguous nucleotides that is complementary to a target15 / 235B1195.70202WO00#14468377 v2sequence (e.g., a target sequence in RHO). In some embodiments, the guide RNA is 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, or 120 nucleotides long. In some embodiments, the guide RNA comprises a sequence of 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, or more contiguous nucleotides that is complementary to a target sequence. Sequence complementarity refers to distinct interactions between adenine and thymine (DNA) or uracil (RNA), and between guanine and cytosine.Linker

[0093] The term “linker,” as used herein, refers to a molecule linking two other molecules or moieties. The linker can be an amino acid sequence in the case of a linker joining two components of a fusion protein. For example, a napDNAbp e.g., a Cas9 protein) can be fused to a polymerase (e.g., a reverse transcriptase) by an amino acid linker sequence. The linker can also be a nucleotide sequence in the case of joining two nucleotide sequences together (e.g., in a gRNA). In other embodiments, the linker is a non-peptidic linker. In some embodiments, the linker is an organic molecule, group, polymer, or chemical moiety. In some embodiments, the linker is 5-200 amino acids in length, for example, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 30-35, 35-40, 40-45, 45-50, 50-60, 60-70, 70-80, 80-90, 90-100, 100-150, or 150-200 amino acids in length. Longer or shorter linkers are also contemplated.napDNAbp

[0094] As used herein, the term “nucleic acid programmable DNA binding protein” or “napDNAbp,” of which Cas proteins such as Cas9 and variants thereof are examples, refers to a protein that uses RNA: DNA hybridization to target and bind to specific sequences in a DNA molecule. Each napDNAbp is associated with at least one guide nucleic acid (e.g., guide RNA), which localizes the napDNAbp to a DNA sequence that comprises a DNA strand (i.e., a target strand) that is complementary to the guide nucleic acid, or a portion thereof (e.g., the protospacer of a guide RNA). In other words, the guide nucleic-acid “programs” the napDNAbp (e.g., Cas9, or a variant thereof) to localize and bind to a complementary sequence.16 / 235B1195.70202WO00#14468377 v2

[0095] Without being bound by theory, the binding mechanism of a napDNAbp-guide RNA complex, in general, includes the step of forming an R-loop whereby the napDNAbp induces the unwinding of a double- strand DNA target, thereby separating the strands in the region bound by the napDNAbp. The guide RNA protospacer then hybridizes to the “target strand.” This displaces a “non-target strand” that is complementary to the target strand, which forms the single strand region of the R-loop. In some embodiments, the napDNAbp includes one or more nuclease activities, which then cut the DNA, leaving various types of lesions. For example, the napDNAbp may comprise a nuclease activity that cuts the non-target strand at a first location, and / or cuts the target strand at a second location. Depending on the nuclease activity, the target DNA can be cut to form a “double- stranded break” whereby both strands are cut. In other embodiments, the target DNA can be cut at only a single site, i.e., the DNA is “nicked” on one strand.Nickase

[0096] As used herein, a “nickase” refers to a napDNAbp (e.g., a Cas9 protein) that is capable of cleaving only one of the two complementary strands of a double- stranded target DNA sequence, thereby generating a nick in that strand. In some embodiments, the nickase cleaves a non-target strand of a double stranded target DNA sequence. In some embodiments, the nickase comprises an amino acid sequence with one or more mutations in a catalytic domain of a canonical napDNAbp (e.g., a Cas9 protein), wherein the one or more mutations reduces or abolishes nuclease activity of the catalytic domain. In some embodiments, the nickase is a Cas9 that comprises one or more mutations in a RuvC-like domain relative to a wild type Cas9 sequence or to an equivalent amino acid position in other Cas9 variants or Cas9 equivalents. In some embodiments, the nickase is a Cas9 that comprises one or more mutations in an HNH-like domain relative to a wild type Cas9 sequence or to an equivalent amino acid position in other Cas9 variants or Cas9 equivalents. In some embodiments, the nickase is a Cas9 that comprises an aspartate-to-alanine substitution (D10A) in the RuvCl catalytic domain of Cas9 relative to a canonical SpCas9 sequence or to an equivalent amino acid position in other Cas9 variants or Cas9 equivalents. In some embodiments, the nickase is a Cas9 that comprises an H840A, N854A, and / or N863A mutation relative to a canonical SpCas9 sequence, or to an equivalent amino acid position in other Cas9 variants or Cas9 equivalents. In some embodiments, the term “Cas9 nickase” refers to a Cas9 with one of the two nuclease domains inactivated. This enzyme is capable of cleaving only one strand of a target DNA. In some embodiments, the nickase is a Cas protein that is not a Cas9 nickase.17 / 235B1195.70202WO00#14468377 v2

[0097] In some embodiments, the napDNAbp of a prime editor is a Cas9 nickase (nCas9) that nicks only a single strand. In other embodiments, the napDNAbp can be selected from the group consisting of: Cas9, Casl2e, Casl2d, Casl2a, Casl2bl, Casl2b2, Casl3a, Casl2c, Casl2d, Casl2e, Casl2h, Casl2i, Casl2g, Casl2f (Casl4), Casl2fl, Casl2j (Cas ), and Argonaute and optionally has a nickase activity such that only one strand is cut. In some embodiments, the napDNAbp is selected from Cas9, Casl2e, Casl2d, Casl2a, Casl2bl, Casl2b2, Casl3a, Casl2c, Casl2d, Casl2e, Casl2h, Casl2i, Casl2g, Casl2f (Casl4), Casl2fl, Casl2j (Cas ), and Argonaute and optionally has a nickase activity such that one DNA strand is cut preferentially with respect to the other DNA strand.Nicking Guide RNA (ngRNA)

[0098] In some embodiments, a guide RNA is a “nicking guide RNA.” Nicking guide RNAs may be used to nick the non-edited strand of a target nucleic acid molecule, which may facilitate incorporation of the edit by cellular DNA repair mechanisms.Nuclear localization sequence (NLS)

[0099] The term “nuclear localization sequence” or “NLS” refers to an amino acid sequence that promotes import of a protein into the cell nucleus, for example, by nuclear transport. Nuclear localization sequences are known in the art and would be apparent to the skilled artisan. For example, NLS sequences are described in Plank et al., international PCT application, PCT / EP2000 / 011690, filed November 23, 2000, published as WO / 2001 / 038547 on May 31, 2001, the contents of which are incorporated herein by reference for its disclosure of exemplary nuclear localization sequences. In some embodiments, a prime editor comprises one or more NLS as described herein. In some embodiments, a prime editor comprises one or more NLS of the sequence KRTADGSEFESPKKKRKV (SEQ ID NO: 1422).Nucleic acid molecule

[0100] The term “nucleic acid,” as used herein, (also referred to as a “polynucleotide”) refers to a polymer of nucleotides. The polymer may include natural nucleosides (z.e., adenosine, thymidine, guanosine, cytidine, uridine, deoxyadenosine, deoxythymidine, deoxyguanosine, and deoxycytidine), nucleoside analogs (e.g., 2-aminoadenosine, 2-thiothymidine, inosine, pyrrolo-pyrimidine, 3-methyl adenosine, 5-methylcytidine, C5 bromouridine, C5 fluorouridine, C5 iodouridine, C5 propynyl uridine, C5 propynyl cytidine, C5 methylcytidine, 7 deazaadenosine, 7 deazaguanosine, 8 oxoadenosine, 8 oxoguanosine, 0(6) methylguanine, 4-acetylcytidine, 5-(carboxyhydroxymethyl)uridine, dihydrouridine, methylpseudouridine, 1-methyl adenosine, 1-methyl guanosine, N6-methyl adenosine, and 2-thiocytidine), chemically18 / 235B1195.70202WO00#14468377 v2modified bases, biologically modified bases (e.g., methylated bases), intercalated bases, modified sugars e.g., 2'-fluororibose, ribose, 2'-deoxyribose, 2'-O-methylcytidine, arabinose, and hexose), or modified phosphate groups (e.g., phosphorothioates and 5' N phosphoramidite linkages).pegRNA

[0101] As used herein, the terms “prime editing guide RNA,” “PEgRNA,” “pegRNA,” or “extended guide RNA” refer to a specialized form of a guide RNA that has been modified to include one or more additional sequences for implementing the prime editing as described herein. As described herein, the prime editing guide RNAs comprise one or more “extended regions,” also referred to herein as “extension arms,” of nucleic acid sequence. The extended regions may comprise, but are not limited to, single- stranded RNA or DNA. Further, the extended regions may occur at the 3' end of a traditional guide RNA. In other arrangements, the extended regions may occur at the 5' end of a traditional guide RNA. In still other arrangements, the extended region may occur at an intramolecular region of the traditional guide RNA, for example, in the gRNA core region which associates and / or binds to the napDNAbp. The extended region comprises a “DNA synthesis template” or “reverse transcriptase template” that encodes (by the polymerase / reverse transcriptase of the prime editor) a single- stranded DNA which, in turn, has been designed to be (a) homologous with the endogenous target DNA to be edited, and (b) which comprises at least one desired nucleotide change (e.g., a transition, a transversion, a deletion, or an insertion) to be introduced or integrated into the endogenous target DNA. The extended region may also comprise other functional sequence elements, such as, but not limited to, a “primer binding site” and a “linker” sequence, or other structural elements, such as, but not limited to, aptamers, stem loops, hairpins, toe-loops (e.g., a 3' toeloop), or an RNA-protein recruitment domain (e.g., MS2 hairpin). As used herein, the “primer binding site” comprises a sequence that hybridizes to a single- strand DNA sequence having a 3' end generated from the nicked DNA of the R-loop.

[0102] In certain embodiments, the pegRNAs have a 3' extension arm, a spacer, and a gRNA core. The 3' extension arm further comprises in the 5' to 3' direction a DNA synthesis template, a primer binding site, and a linker. The DNA synthesis template may also be referred to more broadly as the “DNA synthesis template” where the polymerase of a prime editor described herein is not an RT, but another type of polymerase.19 / 235B1195.70202WO00#14468377 v2

[0103] In certain other embodiments, the pegRNAs have a 5' extension arm, a spacer, and a gRNA core. The 5' extension arm further comprises in the 5' to 3' direction a DNA synthesis template, a primer binding site, and a linker. The DNA synthesis template may also be referred to more broadly as the “DNA synthesis template” where the polymerase of a prime editor described herein is not an RT, but another type of polymerase.

[0104] In still other embodiments, the pegRNAs have in the 5' to 3' direction a spacer, a gRNA core, and an extension arm. The extension arm is at the 3' end of the pegRNA. The extension arm further comprises in the 5' to 3' direction a homology arm, an edit template, and a primer binding site. The extension arm may also comprise an optional modifier region at the 3' and 5' ends, which may be the same sequences or different sequences. In addition, the 3' end of the pegRNA may comprise a transcriptional terminator sequence. These sequence elements of the pegRNAs are further described and defined herein.

[0105] In still other embodiments, the pegRNAs have, in the 5' to 3' direction, an extension arm, a spacer, and a gRNA core. The extension arm is at the 5' end of the pegRNA. The extension arm further comprises in the 3' to 5' direction a primer binding site, an edit template, and a homology arm. The extension arm may also comprise an optional modifier region at the 3' and 5' ends, which may be the same sequences or different sequences. The pegRNAs may also comprise a transcriptional terminator sequence at the 3' end. These sequence elements of the pegRNAs are further described and defined herein.

[0106] In some embodiments, the spacer sequence of the pegRNA is about 10, about 11, about 12, about 13, about 14, about 15, about 16, about 17, about 18, about 19, about 20, about 21, about 22, about 23, about 24, or about 25 nucleotides in length. In certain embodiments, the spacer sequence of the pegRNA is about 20 nucleotides in length. In some embodiments, the primer binding site is about 4, about 5, about 6, about 7, about 8, about 9, about 10, about 11, about 12, about 13, about 14, about 15, about 16, or about 17 nucleotides in length. In certain embodiments, the primer binding site is about 9, about 10, about 11, about 12, about 13, about 14, or about 15 nucleotides in length. In some embodiments, the homology arm of the pegRNA is about 5, about 6, about 7, about 8, about 9, about 10, about 11, about 12, about 13, about 14, about 15, about 16, about 17, about 18, about 19, or about 20 nucleotides in length. In some embodiments, the DNA synthesis template is from about 14 to about 21 nucleotides in length.

[0107] In some embodiments, a pegRNA is an “engineered pegRNA” (“epegRNA”).Relative to a pegRNA, an epegRNA comprises an additional structured motif, for example,20 / 235B1195.70202WO00#14468377 v2attached to its 3' end. Such additional structured motifs may stabilize the pegRNA or otherwise prevent it from being degraded. Suitable structured motifs include, but are not limited to, toe-loops, hairpins, stem-loops, pseudoknots, aptamers, G-quadruplexes, tRNAs, riboswitches, and ribozymes. The terms pegRNA and epegRNA may be used interchangeably herein.

[0108] pegRNAs are further described, e.g., in International Patent Application No.PCT / US2020 / 023721, filed March 19, 2020, which published as WO 2020 / 191239;International Patent Application No. PCT / US2021 / 031439, filed May 7, 2021, which published as WO 2021 / 226558; International Patent Application No. PCT / 2021 / 052097, filed September 24, 2021, which published as WO 2022 / 067130; International Patent Application No. PCT / US2022 / 012054, filed January 11, 2022, which published as WO 2022 / 150790; International Patent Application No. PCT / US2022 / 078655, filed October 25, 2022, which published as WO 2023 / 076898; and International Patent Application No.PCT / US2022 / 074628, filed August 5, 2022, which published as WO 2023 / 015309; the contents of each of which is incorporated by reference herein.

[0109] In the pegRNAs described herein, and any other RNA sequences provided herein, T’ s and U’s may be used interchangeably in the sequences. A person of ordinary skill in the art will understand that T’s in any provided pegRNA or other RNA sequence should be construed as U’s.PE2

[0110] As used herein, “PE2” refers to a PE complex comprising a fusion protein comprising Cas9(H840A) and a variant MMLV RT having the following structure: [NLS]-[Cas9(H840A)]-[linker]-[MMLV_RT(D200N)(T330P)(L603W)(T306K)(W313F)] + a desired pegRNA, wherein the PE fusion has the amino acid sequence of:MKRTADGSEFESPKKKRKVDKKYSIGLDIGTNSVGWAVITDEYKVPSKKFKVLGN TDRHSIKKNLIGALLFDSGETAEATRLKRTARRRYTRRKNRICYLQEIFSNEMAK VDDSFFHRLEESFLVEEDKKHERHPIFGNIVDEVAYHEKYPTIYHLRKKLVDSTD KADLRLIYLALAHMIKFRGHFLIEGDLNPDNSDVDKLFIQLVQTYNQLFEENPIN ASGVDAKAILSARLSKSRRLENLIAQLPGEKKNGLFGNLIALSLGLTPNFKSNFD LAEDAKLQLSKDTYDDDLDNLLAQIGDQYADLFLAAKNLSDAILLSDILRVNTEI TKAPLSASMIKRYDEHHQDLTLLKALVRQQLPEKYKEIFFDQSKNGYAGYIDGG ASQEEFYKFIKPILEKMDGTEELLVKLNREDLLRKQRTFDNGSIPHQIHLGELHA ILRRQEDFYPFLKDNREKIEKILTFRIPYYVGPLARGNSRFAWMTRKSEETITPW NFEEVVDKGASAQSFIERMTNFDKNLPNEKVLPKHSLLYEYFTVYNELTKVKYV TEGMRKPAFLSGEQKKAIVDLLFKTNRKVTVKQLKEDYFKKIECFDSVEISGVE DRFNASLGTYHDLLKIIKDKDFLDNEENEDILEDIVLTLTLFEDREMIEERLKTYA HLFDDKVMKQLKRRRYTGWGRLSRKLINGIRDKQSGKTILDFLKSDGFANRNF MQLIHDDSLTFKEDIQKAQVSGQGDSLHEHIANLAGSPAIKKGILQTVKVVDELV21 / 235B1195.70202WO00#14468377 v2KVMGRHKPENIVIEMARENQTTQKGQKNSRERMKRIEEGIKELGSQILKEHPV ENTQLQNEKLYLYYLQNGRDMYVDQELDINRLSDYDVDAIVPQSFLKDDSIDNK VLTRSDKNRGKSDNVPSEEVVKKMKNYWRQLLNAKLITQRKFDNLTKAERGGL SELDKAGFIKRQLVETRQITKHVAQILDSRMNTKYDENDKLIREVKVITLKSKLV SDFRKDFQFYKVREINNYHHAHDAYLNAVVGTALIKKYPKLESEFVYGDYKVYD VRKMIAKSEQEIGKATAKYFFYSNIMNFFKTEITLANGEIRKRPLIETNGETGEIV WDKGRDFATVRKVLSMPQVNIVKKTEVQTGGFSKESILPKRNSDKLIARKKDW DPKKYGGFDSPTVAYSVLVVAKVEKGKSKKLKSVKELLGITIMERSSFEKNPIDF LEAKGYKEVKKDLIIKLPKYSLFELENGRKRMLASAGELQKGNELALPSKYVNF LYLASHYEKLKGSPEDNEQKQLFVEQHKHYLDEIIEQISEFSKRVILADANLDKV LSAYNKHRDKPIREQAENIIHLFTLTNLGAPAAFKYFDTTIDRKRYTSTKEVLDAT LIHQSITGLYETRIDLSQLGGDSGGSSGGSSGSETPGTSESATPESSGGSSGGSS L NIEDEYRLHETSKEPDVSLGSTWLSDFPQAWAETGGMGLAVRQAPLIIPLKATSTPVSIKQY PMSQEARLG1KPH1QRLLDQG1LVPCQSPWNTPLLPVKKPGTNDYRPVQDLREVNKRVED IHPTVPNPYNLLSGLPPSHQWYTVLDLKDAFFCLRLHPTSQPLFAFEWRDPEMGISGQLT WTRLPQGFKNSPTLFNEALHRDLADFR1QHPDL1LLQYVDDLLLAATSELDCQQGTRALL QTLGNLGYRASAKKAQICQKQVKYLGYLLKEGQRWLTEARKETVMGQPTPKTPRQLREF LGKAGFCRLF1PGFAEMAAPLYPLTKPGTLFNWGPDQQKAYQE1KQALLTAPALGLPDLTK PFELFVDEKQGYAKGVLTQKLGPWRRPVAYLSKKLDPVAAGWPPCLRMVAAIAVLTKDAG KLTMGQPLV1LAPHAVEALVKQPPDRWLSNARMTHYQALLLDTDRVQFGPWALNPATLL PLPEEGLQHNCLDILAEAHGTRPDLTDQPLPDADHTWYTDGSSLLQEGQRKAGAAVTTET EV1WAKALPAGTSAQRAEL1ALTQALKMAEGKKLNVYTDSRYAFATAH1HGE1YRRRGWLTS EGKE1KNKDE1LALLKALFLPKRLS11HCPGHQKGHSAEARGNRMADQAARKAA1TETPDT TLLZE PSGGSKRTADGSEFEPKKKRKV (SEQ ID NO: 1)KEY:NUCLEAR LOCALIZATION SEQUENCE (NLS)CAS9(H840A)33-AMINO ACID LINKERM-MLV reverse transcriptasePE3

[0111] As used herein, “PE3” refers to a prime editing composition comprising a PE2 prime editor and further comprising a second-strand nicking guide RNA that complexes with PE2 and introduces a nick in the non-edit DNA strand in order to induce preferential replacement of the edit strand.PE3b

[0112] As used herein, “PE3b” refers to a prime editing composition comprising PE2 and further comprising a second- strand nicking guide RNA that complexes with PE2 and introduces a nick in the non-edit DNA strand, wherein the second-strand nicking guide RNA is designed for temporal control such that the second strand nick is not introduced until after the installation of the desired edit. This is achieved by designing the second strand nicking guide RNA with a spacer sequence that comprises complementarity to, and only hybridizes with, the edited strand after installation of the desired nucleotide edit(s), but not the endogenous target DNA sequence. Using this strategy, mismatches between the nicking 22 / 235B1195.70202WO00#14468377 v2guide RNA spacer and the unedited target DNA should disfavor nicking by the sgRNA until after the editing event on the PAM strand takes place.PE4

[0113] As used herein, “PE4” refers to a prime editing composition comprising a PE2 and further comprising an MLH1 dominant negative protein variant (z.e., wild- type MLH1 with amino acids 754-756 truncated, which may be referred to herein as “MLH1 A754-756” or “MLHldn”). The MLH1 dominant negative protein variant may be expressed in trans in some embodiments. In some embodiments, a PE4 system comprises a fusion protein comprising a PE2 protein and an MLH1 dominant negative protein joined via an optional linker.PE5 and PE5b

[0114] As used herein, “PE5” refers to a prime editing composition comprising a PE3 prime editor and further comprising an MLH1 dominant negative protein variant (z.e., wild- type MLH1 with amino acids 754-756 truncated, which may be referred to as “MLH1 A754-756” or “MLHldn”). The MLH1 dominant negative variant may be expressed in trans in some embodiments. In some embodiments, a PE5 system comprises a fusion protein comprising a PE2 protein and an MLH1 dominant negative protein joined via an optional linker. “PE5b” refers to a prime editing composition comprising a PE3 and an MLH1 dominant negative protein, wherein the second- strand nicking guide RNA is designed for temporal control such that the second strand nick is not introduced until after the installation of the desired edit. This is achieved by designing the second strand nicking guide RNA with a spacer sequence that comprise complementarity to, and hybridize with, only the edited strand after installation of the desired nucleotide edit(s), but not the endogenous target DNA sequence.PE6

[0115] The term “PE6” refers to a suite of prime editors (PE6a, PE6b, PE6c, PE6d, PE6e, PE6f, and PE6g) comprising improved reverse transcriptase and / or Cas9 variants. The improved reverse transcriptase and Cas9 domains of the PE6 variants can also be combined with each other to offer cumulative benefits. For example, a PE6 prime editor comprising an improved reverse transcriptase variant of PE6a and an improved Cas9 variant of PE6e is referred to herein as the prime editor “PE6a-e” (or “PE6e-a”). Any possible combination of PE6 prime editors is contemplated by the present disclosure including, for example, PE6a-e, PE6a-f, PE6a-g, PE6b-e, PE6b-f, PE6b-g, PE6c-e, PE6c-f, PE6c-g, PE6d-e, PE6d-f, and PE6d-g.23 / 235B1195.70202WO00#14468377 v2

[0116] Any of the PE6 prime editors may also comprise the architecture of the PEmax protein as provided herein. In some embodiments, any of the PE6 prime editors provided herein may further comprise additional amino acid mutations, e.g., any of those included in PEmax as provided herein.

[0117] In some embodiments, a PE6 protein comprises a reverse transcriptase of the following amino acid sequence (the RT domain of “PE6a”), or an amino acid sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the following amino acid sequence:GRPYVTLNLNGMFMDKFKPYSKSNAPITTLEKLSKALSISVEELKAIAELSLDEKYTL KKIPKIDGSKRIVYSLHPKMRLLQSRINERIFKELVVFPSFLFGSVPSKNDVLNSNVKR DYVSCAKAHCGAKTVLKVDISNFFDNIHRDLVRSVFEEILHIKDEALDYLVDICTKDD FVVQGALTSSYIATLCLFAVEGDVVRRAQRKGLVYTRLVDDITVSSKISNYDFSQMQ SHIERMLSEHNLPINKHKTKIFHCSSEPIKVHGLIVDYDSPRLPSDKVKRIRASIHNLKL LAAKNNTKTSVAYRKEFNRCMGRVNELGRVGHEKYESFKKQLQAIKPMPSNRDVA VIDAAIKSLELSYSKGNQNKHWYKRKYDLTRYKMIILTRSESFKEKLECFKSRLASLK PL (SEQ ID NO: 2)

[0118] In some embodiments, a PE6 protein comprises a reverse transcriptase of the following amino acid sequence (the RT domain of “PE6b”), or an amino acid sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the following amino acid sequence:ISSSKHTLSQMNKVSNIVKEPELPDIYKEFKDITADTNTEKLPKPIKGLEFEVELTQEN YRLPIRNYPLTPVKMQAMNDEINQGLKGGIIRESKAINACPVIFVPRKEGTLRMVVDY RPLNKYVKPNVYPLPLIEQLLAKIQGSTIFTKLDLKSAYHQIRVRKGDEHKLAFRCPR GVFEYLVMPYGISTAPAHFQYFINTILGEAKESHVVCYMDDILIHSKSESEHVKHVKD VLQKLKNANLIINQAKCEFHQSQVKFIGYHISEKGLTPCQENIDKVLQWKQPKNRKE LRQFLGSVNYLRKFIPKTSQLTHPLNKLLKKDVRWKWTPTQTQAIENIKQCLVSPPVL RHFDFSKKILLETDVSDVAVGAVLSQKHDDDKYYPVGYYSAKMSKAQLNYSVSDK EMLAIIKSLEHWRHYLESTIEPFKILTDHRNLIGRITNESEPENKRLARWQLFLQDFNF EINYRPGSANHIADALSRIVDETEPIPKDNEDNSINFVNQISI (SEQ ID NO: 3)

[0119] In some embodiments, a PE6 protein comprises a reverse transcriptase of the following amino acid sequence (the RT domain of “PE6c”), or an amino acid sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the following amino acid sequence:24 / 235B1195.70202WO00#14468377 v2ISSSKHTLSQMNKVSNIVKEPELPDIYKEFKDITADTNTEKLPKPIKGLEFEVELTQEN YRLPIRNYPLTPVKMQAMNDEINQGLKGGIIRESKAINACPVIFVPRKEGTLRMVVDY RPLNKYVKPNVYPLPLIEQLLAKIQGSTIFTKLDLKSAYHQIRVRKGDEHKLAFRCPR GVFEYLVMPYGIKTAPAHFQYFINTILGEAKESHVVCYMDDILIHSKSESEHVKHVKD VLQKLKNANLIINQAKCEFHQSQVKFLGYHISEKGLTPCQENIDKVLQWKQPKNQKE LRQFLGQVNYLRKFIPKTSQLTHPLNKLLKKDVRWKWTPTQTQAIENIKQCLVSPPV LRHFDFSKKILLETDVSDVAVGAVLSQKHDDDKYYPVGYYSAKMSKAQLNYSVSD KEMLAIIKSLEHWRHYLESTIEPFKILTDHRNLIGRITNESEPENKRLARWQLFLQDFN FEINYRPGSANHIADALSRIVDETEPIPKDNEDNSINFVNQISI (SEQ ID NO: 4)

[0120] In some embodiments, a PE6 protein comprises a reverse transcriptase comprising the following amino acid sequence (the RT domain of “PE6d”), or an amino acid sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the following amino acid sequence:TLNIEDEYRLHETSKEPDVSLGSTWLSDFPQAWAETGGMGLAVRQAPLIIPLKATSTP VSIKQYPMSQEARLGIKPHIQRLLDQGILVPCQSPWNTPLLPVKKPGTNDYRPVQDLR EVNKRVEDIHPNVPNPYNLLSGLPPSHQWYTVLDLKDAFFCLRLHPTSQPLFAFEWR DPEMGISGQLTWTRLPQGFKNSPTLFCEALHRDLADFRIQHPDLILLQYYDDLLLAAT SELDCQQGTRALLQTLGNLGYRASAKKAQICQKQVKYLGYLLKEGQRWLTEARKE TVMGQPTPKTPRQLREFLGKAGFCRLFIPGFAEMAAPLYPLTKPGTLFNWGPDQQKA YQEIKQALLTAPALGLPDLTKPFELFVDEKQGYAKGVLTQKLGPWRRPVAYLSKKL DPVAAGWPPCLRMVAAIAVLTKDAGKLTMGQPLVILAPHAVEALVKQPPDRWLSN ARMTHYQALLLDTDRVQFGPVVALNPATLLPLPEEGLQHNCLD (SEQ ID NO: 5)

[0121] In some embodiments, a PE6 protein comprises a Cas9 protein of the following amino acid sequence (the Cas9 domain of “PE6e”), or an amino acid sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the following amino acid sequence:MDKKYSIGLDIGTNSVGWAVITDEYKVPSKKFKVLGNTDRHSIKKNLIGALLFDSGE TAEATRLKRTARRRYTRRKNRICYLQEIFSNEMAKVDDSFFHRLEESFLVEEDKKHE RHPIFGNIVDEVAYHEKYPTIYHLRKKLVDSTDKADLRLIYLALAHMIKFRGHFLIEG DLNPDNSDVDKLFIQLVQTYNQLFEENPINASGVDAKAILSARLSKSRRLENLIAQLP GEKKNGLFGNLIALSLGLTPNFKSNFDLAEDAKLQLSKDTYDDDLDNLLAQIGDQYA DLFLAAKNLSDAILLSDILRVNTEITKAPLSASMIKRYDEHHQDLTLLKALVRQQLPE KYKEIFFDQSKNGYAGYIDGGASQEEFYKFIKPILEKMDGTEELLVKLNREDLLRKQR25 / 235B1195.70202WO00#14468377 v2TFDNGSIPHQIHLGELHAILRRQEDFYPFLKDNREKIEKILTFRIPYYVGPLARGNSRFA WMTRKSEETITPWNFEEVVDKGASAQSFIERMTNFDKNLPNEKVLPKHSLLYEYFTV YNELTKVKYVTEGMRKPAFLSGEQKKAIVDLLFKTNRKVTVKQLKEDYFKKIECFD SVEISGVEDRFNASLGTYHDLLKIIKDKDFLDNEENEDILEDIVLTLTLFEDREMIEERL KTYAHLFDDKVMKQLKRRRYTGWGRLSRKLINGIRDKQSGKTILDFLKSDGFANRN FMQLIHDDSLTFKEDIQKAQVSGQGDSLHEHIANLAGSPAIKKGILQTVKVVDELVK VMGRHKPENIVIEMARENQTTQKGQRNSRERMKRIEEGIKELGSQILKEHPVENTQL QNEKLYLYYLQNGRDMYVDQELDINRLSDYDVDAIVPQSFLKDDSIDNKVLTRSDK NRGKSDNVPSEEVVKKMKNYWRQLLNAKLITQRKFDNLTKAERGGLSELDKAGFIA RQLVETRQITKHVAQILDSRMNTKYDENDKLIREVKVITLKSKLVSDFRKDFQFYKV REINNYHHAHDAYLNAVVGTALIKKYPKLESEFVYGDYKVYDVRKMIAKSEQEIGK ATAKYFFYSNIMNFFKTEITLANGEIRKRPLIETNGETGEIVWDKGRDFATVRKVLSM PQVNIVKKTEVQTGGFSKESILPKRNSDKLIARKKDWDPKKYGGFDSPTVAYSVLVV AKVEKGKSKKLKSVKELLGITIMERSSFEKNPIDFLEAKGYKEVKKDLIIKLPKYSLFE LENGRKRMLASAGELQKGNELALPSKYVNFLYLASHYEKLKGSPEDNEQKQLFVEQ HKHYLDEIIEQISEFSKRVILADANLDKVLSAYNKHRDKPIREQAENIIHLFTLTNLGA PAAFKYFDTTIDRKRYTSTKEVLDATLIHQSITGLYETRIDLSQLGGD (SEQ ID NO: 6)

[0122] In some embodiments, a PE6 protein comprises a Cas9 protein of the following amino acid sequence (the Cas9 domain of “PE6f”), or an amino acid sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the following amino acid sequence:MDKKYSIGLDIGTNSVGWAVITDEYKVPSKKFKVLGNTDRHSIKKNLIGALLFDSGE TAEATRLKRTARRRYTRRKNRICYLQEIFSNEMAKVDDSFFRRLEESFLVEEDKKHE RHPIFGNIVDEVAYHEKYPTIYHLRKKLVDSTDKADLRLIYLALAHMIKFRGHFLIEG DLNPDNSDVDKLFIQLVQTYNQLFEENPINASGVDAKAILSARLSKSRRLENLIAQLP GEKKNGLFGNLIALSLGLTPNFKSNFDLAEDAKLQLSKDTYDDDLDNLLAQIGDQYA DLFLAAKNLSDAILLSDILRVNTEITKAPLSASMIKRYDEHHQDLTLLKALVRQQLPE KYKEIFFDQSKNGYAGYIDGGASQEEFYKFIKPILEKMDGTEELLVKLNREDLLRKQR TFDNGSIPHQIHLGELHAILRRQEDFYPFLKDNREKIEKILTFRIPYYVGPLARGNSRFA WMTRKSEKTITPWNFEEVVDKGASAQSFIERMTNFDKNLPNEKVLPKHSLLYEYFTV YNELTKVKYVTEGMRKPAFLSGEQKKAIVDLLFKTNRKVTVKQLKEDYFKKIECFD SVEISGVEDRFNASLGTYHDLLKIIKDKDFLDNEENEDILEDIVLTLTLFEDREMVEER LKTYAHLFDNKVMKQLKRRRYTGWGRLSRKLINGIRDKQSGKTILDFLKSDGFANR26 / 235B1195.70202WO00#14468377 v2NFMQLIHDDSLTFKEDIQKAQVSGQGDSLYEHIANLAGSPAIKKGILQTVKVVDELV KVMGRHKPENIVIEMARENQTTQKGQKNSRERMKRIEEGIKELGSQILKEHPVENTQ LQNEKLYLYYLQNGRDMYVDQELDINRLSDYDVDAIVPQSFLKDDSIDNKVLTRSD KNRGKSDNVPSEEVVKKMKNYWRQLLNAKLITQRKFDNLTKAERGGLSELDKAGFI ARQLVETRQITKHVAQILDSRMNTKYDENDKLIREVKVITLKSKLVSDFRKDFQFYK VREINNYHHAHDAYLNAVVGTALIKKYPKLESEFVYGDYKVYDVRKMIAKSEQEIG KATAKYFFYSNIMNFFKTEITLANGEIRKRPLIETNGETGEIVWDKGRDFATVRKVLS MPQVNIVKKTEVQTGGFSKESILPKRNSDKLIARKKDWDPKKYGGFDSPTVAYSVLV VAKVEKGKSKKLKSVKELLGITIMERSSFEKNPIDFLEAKGYKEVKKDLIIKLPKYSLF ELENGRKRMLASAGELQKGNELALPSKYVNFLYLASHYEKLKGSPEDNEQKQLFVE QHKHYLDEIIEQISEFSKRVILADANLDKVLSAYNKHRDKPIREQAENIIHLFTLTNLG APAAFKYFDTTIDRKRYTSTKEVLDATLIHQSITGLYETRIDLSQLGGD (SEQ ID NO: 7)

[0123] In some embodiments, a PE6 protein comprises a Cas9 protein of the following amino acid sequence (the Cas9 domain of “PE6g”), or an amino acid sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the following amino acid sequence:MDKKYSIGLDIGTNSVGWAVITDEYKVPSKKFKVLGNTDRHSIKKNLIGALLFDSGE TAEATRLKRTARRRYTRRKNRICYLQEIFSNEMAKVDDSFFRRLEESFLVEEDKKHE RHPIFGNIVDEVAYHEKYPTIYHLRKKLVDSTDKADLRLIYLALAHMIKFRGHFLIEG DLNPDNSDVDKLFIQLVQTYNQLFEENPINASGVDAKAILSARLSKSRRLENLIAQLP GEKKNGLFGNLIALSLGLTPNFKSNFDLAEDAKLQLSKDTYDDDLDNLLAQIGDQYA DLFLAAKNLSDAILLSDILRVNTEITKAPLSASMIKRYDEHHQDLTLLKALVRQQLPE KYKEIFFDQSKNGYAGYIDGGASQEEFYKFIKPILEKMDGTEELLVKLNREDLLRKQR TFDNGSIPHQIHLGELHAILRRQEDFYPFLKDNREKIEKILTFRIPYYVGPLARGNSRFA WMTRKSEKTITPWNFEEVVDKGASAQSFIERMTNFDKNLPNEKVLPKHSLLYEYFTV YNELTKVKYVTEGMRKPAFLSGEQKKAIVDLLFKTNRKVTVKQLKEDYFKKIECFD SVEISGVEDRFNASLGTYHDLLKIIKDKDFLDNEENEDILEDIVLTLTLFEDREMVEER LKTYAHLFDNKVMKQLKRCRYTGWGRLSRKLINGIRDKQSGKTILDFLKSDGFANR NFMQLIHDDSLTFKEDIQKAQVSGQGDSLYEHIANLAGSPAIKKGILQTVKVVDELV KVMGRHKPENIVIEMARENQTTQKGQKNSRERMKRIEEGIKELGSQILKEHPVENTQ LQNEKLYLYYLQNGRDMYVDQELDINRLSDYDVDAIVPQSFLKDDSIDNKVLTRSD KNRGKSDNVPSEEVVKKMKNYWRQLLNAKLITQRKFDNLTKAERGGLSELDKAGFI27 / 235B1195.70202WO00#14468377 v2KRQLVETRQITKHVAQILDSRMNTKYDENDKLIREVKVITLKSKLVSDFRKDFQFYK VREINNYHHAHDAYLNAVVGTALIKKYPKLESEFVYGDYKVYDVRKMIAKSEQEIG KATAKYFFYSNIMNFFKTEITLANGEIRKRPLIETNGETGEIVWDKGRDFATVRKVLS MPQVNIVKKTEVQTGGFSKESILPKRNSDKLIARKKDWDPKKYGGFDSPTVAYSVLV VAKVEKGKSKKLKSVKELLGITIMERSSFEKNPIDFLEAKGYKEVKKDLIIKLPKYSLF ELENGRKRMLASAGELQKGNELALPSKYVNFLYLASHYEKLKGSPEDNEQKQLFVE QHKHYLDEIIEQISEFSKRVILADANLDKVLSAYNKHRDKPIREQAENIIHLFTLTNLG APAAFKYFDTTIDRKRYTSTKEVLDATLIHQSITGLYETRIDLSQLGGD (SEQ ID NO: 8)PE7

[0124] The term “PE7” refers to the PE6 prime editors plus a second strand nicking guide RNA. For example, “PE7a” refers to the PE6a prime editor as provided herein, plus a second strand nicking guide RNA.PEmax

[0125] As used herein, “PEmax” refers to a prime editing composition comprising 1) a fusion protein comprising a Cas9 protein variant Cas9(R221K N39K H840A) and a variant MMLV RT having the following structure: [bipartite NLS]-[Cas9(R221K)(N394K)(H840A)]-[linker]-[MMLV_RT(D200N)(T330P)(L603W)]-[bipartite NLS]-[NLS] and 2) a desired PEgRNA, wherein the fusion protein (referred to as the PEmax protein) has the following amino acid sequence:MKRTADGSEFESPKKKRKVDKKYSIGLDIGTNSVGWAVITDEYKVPSKKFKVLG NTDRHSIKKNLIGALLFDSGETAEATRLKRTARRRYTRRKNRICYLQEIFSNEMA KVDDSFFHRLEESFLVEEDKKHERHPIFGNIVDEVAYHEKYPTIYHLRKKLVDST DKADLRLIYLALAHMIKFRGHFLIEGDLNPDNSDVDKLFIQLVQTYNQLFEENPI NASGVDAKAILSARLSKSRKLENLIAQLPGEKKNGLFGNLIALSLGLTPNFKSNF DLAEDAKLQLSKDTYDDDLDNLLAQIGDQYADLFLAAKNLSDAILLSDILRVNT EITKAPLSASMIKRYDEHHQDLTLLKALVRQQLPEKYKEIFFDQSKNGYAGYID GGASQEEFYKFIKPILEKMDGTEELLVKLKREDLLRKQRTFDNGSIPHQIHLGE LHAILRRQEDFYPFLKDNREKIEKILTFRIPYYVGPLARGNSRFAWMTRKSEETI TPWNFEEVVDKGASAQSFIERMTNFDKNLPNEKVLPKHSLLYEYFTVYNELTKV KYVTEGMRKPAFLSGEQKKAIVDLLFKTNRKVTVKQLKEDYFKKIECFDSVEIS GVEDRFNASLGTYHDLLKIIKDKDFLDNEENEDILEDIVLTLTLFEDREMIEERL KTYAHLFDDKVMKQLKRRRYTGWGRLSRKLINGIRDKQSGKTILDFLKSDGFA NRNFMQLIHDDSLTFKEDIQKAQVSGQGDSLHEHIANLAGSPAIKKGILQTVKV VDELVKVMGRHKPENIVIEMARENQTTQKGQKNSRERMKRIEEGIKELGSQIL KEHPVENTQLQNEKLYLYYLQNGRDMYVDQELDINRLSDYDVDAIVPQSFLKD DSIDNKVLTRSDKNRGKSDNVPSEEVVKKMKNYWRQLLNAKLITQRKFDNLTK AERGGLSELDKAGFIKRQLVETRQITKHVAQILDSRMNTKYDENDKLIREVKVI TLKSKLVSDFRKDFQFYKVREINNYHHAHDAYLNAVVGTALIKKYPKLESEFVY GDYKVYDVRKMIAKSEQEIGKATAKYFFYSNIMNFFKTEITLANGEIRKRPLIET28 / 235B1195.70202WO00#14468377 v2NGETGEIVWDKGRDFATVRKVLSMPQVNIVKKTEVQTGGFSKESILPKRNSDKL IARKKDWDPKKYGGFDSPTVAYSVLVVAKVEKGKSKKLKSVKELLGITIMERSS FEKNPIDFLEAKGYKEVKKDLIIKLPKYSLFELENGRKRMLASAGELQKGNELA LPSKYVNFLYLASHYEKLKGSPEDNEQKQLFVEQHKHYLDEIIEQISEFSKRVIL ADANLDKVLSAYNKHRDKPIREQAENIIHLFTLTNLGAPAAFKYFDTTIDRKRYT STKEVLDATLIHQSITGLYETRIDLSOLGGDSGGSSGGSKRTADGSEFESPKKKR KVSGGSSGGSTLNIEDEYRLHETSKEPDVSLGSTWLSDFPOAWAETGGMGLAVRQA PLIIPLKATSTPVSIKQYPMSQEARLGIKPHIQRLLDQGILVPCQSPWNTPLLPVKKPGT NDYRPVQDLREVNKRVEDIHPTVPNPYNLLSGLPPSHQWYTVLDLKDAFFCLRLHPT SQPLFAFEWRDPEMGISGQLTWTRLPQGFKNSPTLFNEALHRDLADFRIQHPDLILLQ YVDDLLLAATSELDCQQGTRALLQTLGNLGYRASAKKAQICQKQVKYLGYLLKEG QRWLTEARKETVMGQPTPKTPRQLREFLGKAGFCRLFIPGFAEMAAPLYPLTKPGTL FNWGPDQQKAYQEIKQALLTAPALGLPDLTKPFELFVDEKQGYAKGVLTQKLGPWR RPVAYLSKKLDPVAAGWPPCLRMVAAIAVLTKDAGKLTMGQPLVILAPHAVEALV KQPPDRWLSNARMTHYQALLLDTDRVQFGPVVALNPATLLPLPEEGLQHNCLDILA EAHGTRPDLTDQPLPDADHTWYTDGSSLLQEGQRKAGAAVTTETEVIWAKALPAGT SAQRAELIALTQALKMAEGKKLNVYTDSRYAFATAHIHGEIYRRRGWLTSEGKEIKN KDEILALLKALFLPKRLSIIHCPGHQKGHSAEARGNRMADQAARKAAITETPDTSTLLlENSSP. S'GG. S'KRTADGSEFESPKKKRKVG. S'GP / M W / . D (SEQ ID NO: 9)KEY:BIPARTITE SV40 NUCLEAR LOCALIZATION SEQUENCE (NLS).CAS9(R221K N39K H840A)SGGSx2-BIPARTITE SV40NLS-SGGSx2 LINKERM-MLV reverse transcriptase(D200N T306K W313F T330P L603W)Other linker sequenceBIPARTITE SV40NLSOther linker sequencec-Myc NLSPrime editing

[0126] As used herein, the term “prime editing” refers to an approach for gene editing using napDNAbps, a polymerase (e.g., a reverse transcriptase), and specialized guide RNAs that include a primer binding site and a DNA synthesis template for encoding desired new genetic information (or deleting genetic information) that is then incorporated into a target DNA sequence. Prime editing is described in Anzalone, A. V. et al., Search-and-replace genome editing without double-strand breaks or donor DNA. Nature 576, 149-157 (2019), which is incorporated herein by reference. See also International PCT Application, PCT / US2020 / 023721, filed March 19, 2020, and published as WO 2020 / 191239, which is incorporated herein by reference.29 / 235B1195.70202WO00#14468377 v2

[0127] Prime editing represents a platform for genome editing that is a versatile and precise method to directly write new genetic information into a specified DNA site using a nucleic acid programmable DNA binding protein (“napDNAbp”) working in association with a polymerase (z.e., in the form of a fusion protein or otherwise provided in trans with the napDNAbp), wherein the prime editing system is programmed with a prime editing (PE) guide RNA (“pegRNA”) that both specifies the target site and templates the synthesis of the desired edit in the form of a replacement DNA strand by way of an extension (either DNA or RNA) engineered onto a guide RNA (e.g., at the 5' or 3' end, or at an internal portion of a guide RNA). The replacement strand containing the desired edit (e.g., a single nucleobase substitution) shares the same sequence as the endogenous strand (or is homologous to it) immediately downstream of the nick site of the target site to be edited (with the exception that it includes the desired edit). Through DNA repair and / or replication machinery, the endogenous strand downstream of the nick site is replaced by the newly synthesized replacement strand containing the desired edit. In some cases, prime editing may be thought of as a “search-and-replace” genome editing technology since the prime editors, as described herein, not only search and locate the desired target site to be edited, but at the same time, encode a replacement strand containing a desired edit that is installed in place of the corresponding target site endogenous DNA strand. The prime editors of the present disclosure relate, in part, to the discovery that the mechanism of target-primed reverse transcription (TPRT) or “prime editing” can be leveraged or adapted for conducting precision CRISPR / Cas-based genome editing with high efficiency and genetic flexibility. TPRT is naturally used by mobile DNA elements, such as mammalian non-LTR retrotransposons and bacterial Group II introns. Cas protein-reverse transcriptase fusions or related systems are used to target a specific DNA sequence with a guide RNA, generate a single strand nick at the target site, and use the nicked DNA as a primer for reverse transcription of an engineered DNA synthesis template that is integrated with the guide RNA. However, while the concept begins with prime editors that use reverse transcriptase as the DNA polymerase component, the prime editors described herein are not limited to reverse transcriptases but may include the use of virtually any DNA polymerase. Indeed, while the application throughout may refer to prime editors with “reverse transcriptases,” it is set forth here that reverse transcriptases are only one type of DNA polymerase that may work with prime editing. Thus, wherever the specification mentions a “reverse transcriptase,” the person having ordinary skill in the art should appreciate that any suitable DNA polymerase may be used in place of the reverse30 / 235B1195.70202WO00#14468377 v2transcriptase. Thus, in one aspect, the prime editors may comprise Cas9 (or an equivalent napDNAbp), which is programmed to target a DNA sequence by associating it with a specialized guide RNA (z.e., pegRNA) containing a spacer sequence that anneals to a complementary sequence (the complementary sequence to an endogenous protospacer sequence) in the target DNA. The pegRNA also contains new genetic information in the form of an extension that encodes a replacement strand of DNA containing a desired nucleotide change which is used to replace a corresponding endogenous DNA strand at the target site. To transfer information from the pegRNA to the target DNA, the mechanism of prime editing involves nicking the target site in one strand of the DNA to expose a 3 '-hydroxyl group. The exposed 3 '-hydroxyl group can then be used to prime the DNA polymerization of the editencoding extension on pegRNA directly into the target site. In various embodiments, the extension — which provides the template for polymerization of the replacement strand containing the edit — can be formed from RNA or DNA. In the case of an RNA extension, the polymerase of the prime editor can be an RNA-dependent DNA polymerase (such as a reverse transcriptase). In the case of a DNA extension, the polymerase of the prime editor may be a DNA-dependent DNA polymerase. The newly synthesized strand (z.e., the replacement DNA strand containing the desired nucleotide edit) that is formed by the prime editor would be homologous to the genomic target sequence (z.e., have the same sequence as), except for the inclusion of one or more desired nucleotide changes (e.g., a single nucleotide substitution, a deletion, or an insertion, or a combination thereof). The newly synthesized (or replacement) strand of DNA may also be referred to as a single strand DNA flap, which would compete for hybridization with the complementary homologous endogenous DNA strand, thereby displacing the corresponding endogenous strand.Resolution of the hybridized intermediate (also referred to as a heteroduplex, comprising the single strand DNA flap synthesized by the reverse transcriptase hybridized to the endogenous DNA strand with the exception of mismatches at positions where desired nucleotide edits are installed in the edit strand) can include removal of the resulting displaced flap of endogenous DNA (e.g., with a 5' end DNA flap endonuclease, FEN1), ligation of the synthesized single strand DNA flap to the target DNA, and assimilation of the desired nucleotide changes as a result of cellular DNA repair and / or replication processes.

[0128] In various embodiments, prime editing operates by contacting a target DNA molecule (for which a change in the nucleotide sequence is desired to be introduced) with a nucleic acid programmable DNA binding protein (napDNAbp) complexed with a prime editing guide31 / 235B1195.70202WO00#14468377 v2RNA (pegRNA). In various embodiments, the prime editing guide RNA (pegRNA) comprises an extension at the 3' or 5' end of the guide RNA, or at an intramolecular location in the guide RNA, and encodes the desired nucleotide change (e.g., single nucleotide substitution, insertion, or deletion). First, the napDNAbp / extended gRNA complex contacts the DNA molecule, and the extended gRNA guides the napDNAbp to bind to a target locus. Next, a nick in one of the strands of DNA of the target locus is introduced (e.g., by a nuclease or chemical agent), thereby creating an available 3' end in one of the strands of the target locus. In certain embodiments, the nick is created in the strand of DNA that corresponds to the R-loop strand, i.e., the strand that is not hybridized to the guide RNA sequence, i.e., the “non-target strand.” The nick, however, could be introduced in either of the strands. That is, the nick could be introduced into the R-loop “target strand” (i.e., the strand hybridized to the protospacer of the extended gRNA) or the “non-target strand” (i.e., the strand forming the single- stranded portion of the R-loop and which is complementary to the target strand). In the next step, the 3' end of the DNA strand (formed by the nick) interacts with the extended portion of the guide RNA in order to prime reverse transcription (i.e., “target- primed RT”). In certain embodiments, the 3' end DNA strand hybridizes to a specific RT priming sequence on the extended portion of the guide RNA, i.e., the “reverse transcriptase priming sequence” or “primer binding site” on the pegRNA. In the next step, a reverse transcriptase (or other suitable DNA polymerase) is introduced that synthesizes a single strand of DNA from the 3' end of the primed site towards the 5' end of the prime editing guide RNA. The DNA polymerase (e.g., reverse transcriptase) can be fused to the napDNAbp or alternatively can be provided in trans to the napDNAbp. This forms a single-strand DNA flap comprising the desired nucleotide change (e.g., the single base change, insertion, or deletion, or a combination thereof) and that is otherwise homologous to the endogenous DNA at or adjacent to the nick site. In the next step, the napDNAbp and guide RNA are released. The final two steps relate to the resolution of the single strand DNA flap such that the desired nucleotide change becomes incorporated into the target locus. This process can be driven towards the desired product formation by removing the corresponding 5' endogenous DNA flap that forms once the 3' single strand DNA flap invades and hybridizes to the endogenous DNA sequence. Without being bound by theory, the cell’s endogenous DNA repair and replication processes resolve the mismatched DNA to incorporate the nucleotide change(s) to form the desired altered product. The process can also be driven towards product formation32 / 235B1195.70202WO00#14468377 v2with “second strand nicking.” This process may introduce at least one or more of the following genetic changes: transversions, transitions, deletions, and insertions.Prime editor

[0129] The term “prime editor” refers to the polypeptide or polypeptide components involved in prime editing as described herein. In some embodiments, a prime editor comprises a fusion construct comprising a napDNAbp (e.g., Cas9 nickase, and / or any of the Cas9 variants provided herein) and a reverse transcriptase (e.g., any of the reverse transcriptase variants provided herein). In some embodiments, a prime editor is capable of carrying out prime editing on a target nucleotide sequence in the presence of a pegRNA (or “extended guide RNA”). In some embodiments, a prime editor comprises a napDNAbp (e.g., Cas9 nickase) and a reverse transcriptase provided in trans, i.e., the napDNAbp and the reverse transcriptase are not fused. The in trans napDNAbp and the reverse transcriptase may be tethered via a non-peptide linkage, e.g., an MS2 RNA-protein binding RNA sequence and a MS2 coat protein fused to either the napDNAbp or the reverse transcriptase, or may be unlinked to each other and simply recruited by the pegRNA. In some embodiments, a prime editor composition, system, or complex provided herein comprises a fusion protein or a fusion protein complexed with a pegRNA, and / or further complexed with a second-strand nicking sgRNA. In some embodiments, the prime editor system may also refer to the complex comprising a fusion protein (reverse transcriptase fused to a napDNAbp), a pegRNA, and a regular guide RNA capable of directing the second-site nicking step of the non-edited strand as described herein.Primer binding site (PBS)

[0130] The term “primer binding site” or “the PBS” refers to the nucleotide sequence located on a pegRNA as component of the extension arm (typically at the 3' end of the extension arm) and serves to bind to the primer sequence that is formed after Cas9 nicking of the target sequence by the prime editor. As detailed elsewhere, when the Cas9 nickase component of a prime editor nicks one strand of the target DNA sequence, a 3 '-ended ssDNA flap is formed, which serves a primer sequence that anneals to the primer binding site on the pegRNA to prime reverse transcription.Protein, peptide, and polypeptide

[0131] The terms “protein,” “peptide,” and “polypeptide” are used interchangeably herein and refer to a polymer of amino acid residues linked together by peptide (amide) bonds. The terms refer to a protein, peptide, or polypeptide of any size, structure, or function. Typically,33 / 235B1195.70202WO00#14468377 v2a protein, peptide, or polypeptide will be at least three amino acids long. A protein, peptide, or polypeptide may refer to an individual protein, or a collection of proteins. One or more of the amino acids in a protein, peptide, or polypeptide may be modified, for example, by the addition of a chemical entity such as a carbohydrate group, a hydroxyl group, a phosphate group, a famesyl group, an isofamesyl group, a fatty acid group, a linker for conjugation, functionalization, or other modification, etc. A protein, peptide, or polypeptide may also be a single molecule or may be a multi-molecular complex. A protein, peptide, or polypeptide may be just a fragment of a naturally occurring protein or peptide. A protein, peptide, or polypeptide may be naturally occurring, recombinant, or synthetic, or any combination thereof. Any of the proteins provided herein may be produced by any method known in the art. For example, the proteins provided herein may be produced via recombinant protein expression and purification, which is especially suited for fusion proteins comprising a peptide linker. Methods for recombinant protein expression and purification are well known, and include those described by Green and Sambrook, Molecular Cloning: A Laboratory Manual (4th ed., Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N. Y. (2012)), the contents of which are incorporated herein by reference.Protospacer

[0132] As used herein, the term “protospacer” refers to the sequence (often, but not always, of ~20 bp) in DNA adjacent to the PAM (protospacer adjacent motif) sequence. The protospacer shares the same sequence as the spacer sequence of the guide RNA. The guide RNA anneals to the complement of the protospacer sequence on the target DNA (specifically, one strand thereof, i.e., the “target strand” versus the “non-target strand” of the target DNA sequence). The skilled person will appreciate that the literature in the state of the art sometimes refers to the “protospacer” as the ~20-nt target- specific guide sequence on the guide RNA itself, rather than referring to it as a “spacer.” Thus, in some cases, the term “protospacer” as used herein may be used interchangeably with the term “spacer.” The context of the description surrounding the appearance of either “protospacer” or “spacer” will help inform the reader as to whether the term is in reference to the gRNA or the DNA target.Protospacer adjacent motif (PAM)

[0133] As used herein, the term “protospacer adjacent motif’ or “PAM” refers to a DNA sequence (e.g., an approximately 2-6 nucleotide sequence) that is an important targeting component of a Cas nuclease, e.g., a Cas9. For example, in some embodiments for a Cas9 nuclease, the PAM sequence is on either strand and is downstream in the 5' to 3' direction of34 / 235B1195.70202WO00#14468377 v2the Cas9 cut site. The canonical PAM sequence (z.e., the PAM sequence that is associated with the Cas9 nuclease of Streptococcus pyogenes or SpCas9) is 5'-NGG-3', wherein “N” is any nucleobase followed by two guanine (“G”) nucleobases. In some embodiments, SpCas9 can also recognize additional non-canonical PAMs (e.g., NAG and NGA).

[0134] Different PAM sequences can be associated with different Cas9 nucleases or equivalent proteins from different organisms. In addition, any given Cas9 nuclease, e.g., SpCas9, may be modified to alter the PAM specificity of the nuclease such that the nuclease recognizes an alternative PAM sequence.Reverse transcriptase

[0135] The term “reverse transcriptase” describes a class of polymerases characterized as RNA-dependent DNA polymerases. All known reverse transcriptases require a primer to synthesize a DNA transcript from an RNA template. Historically, reverse transcriptase has been used primarily to transcribe mRNA into cDNA, which can then be cloned into a vector for further manipulation. Avian myoblastosis virus (AMV) reverse transcriptase was the first widely used RNA-dependent DNA polymerase (Verma, Biochim. Biophys. Acta 473:1 (1977)). The enzyme has 5'-3' RNA-directed DNA polymerase activity, 5'-3' DNA-directed DNA polymerase activity, and RNase H activity. RNase H is a processive 5' and 3' ribonuclease specific for the RNA strand for RNA-DNA hybrids (Perbal, A Practical Guide to Molecular Cloning, New York: Wiley & Sons (1984)). Errors in transcription cannot be corrected by reverse transcriptase because known viral reverse transcriptases lack the 3 '-5' exonuclease activity necessary for proofreading (Saunders and Saunders, Microbial Genetics Applied to Biotechnology, London: Croom Helm (1987)). A detailed study of the activity of AMV reverse transcriptase and its associated RNaseH activity has been presented by Berger et al., Biochemistry 22:2365-2372 (1983). Another reverse transcriptase that is used extensively in molecular biology is reverse transcriptase originating from Moloney murine leukemia virus (M-MLV or “MMLV”). See, e.g., Gerard, G. R., DNA 5:271-279 (1986) and Kotewicz, M. L., et al., Gene 35:249-258 (1985). M-MLV reverse transcriptase substantially lacking in RNase H activity has also been described. See, e.g., U. S. Pat. No. 5,244,797. The invention contemplates the use of any such reverse transcriptases, or variants or mutants thereof.Retinitis pigmentosa

[0136] “Retinitis pigmentosa” is a genetic disorder of the eyes that causes progressive loss of vision. It is estimated to affect approximately 1 in 4000 people. Symptoms of retinitis35 / 235B1195.70202WO00#14468377 v2pigmentosa include difficulty seeing at night, decreasing peripheral vision, and tunnel vision. In severe cases, retinitis pigmentosa can lead to complete blindness, although this is not common. Mutations in nearly 100 different genes have been found to cause retinitis pigmentosa. In some instances, a mutation in the RHO gene encoding rhodopsin causes retinitis pigmentosa. For example, a mutation in the RHO gene that results in a P23H mutation in the RHO protein has been found to cause retinitis pigmentosa. Retinitis pigmentosa is further described, for example, in Kamde et al., Retinitis Pigmentosa:Pathogenesis, Diagnostic Findings, and Treatment. Cureus 2003, 15(10): e48006., which is incorporated herein by reference.Rhodopsin (RHO)

[0137] Rhodopsin (RHO) is a protein encoded by the RHO gene. It is a light-sensitive G-protein-coupled receptor found in the rod cells in the retina. Mutations in the RHO protein, including the mutation P23H, have been found to cause retinitis pigmentosa. In some embodiments, the RHO gene and / or RHO protein referenced herein are the human gene and / or protein.

[0138] The sequence of the RHO gene that encodes rhodopsin is as follows (GenBank Accession No. 009115):ATGAATGGCACAGAAGGCCCTAACTTCTACGTGCCCTTCTCCAATGCGACGGGTG TGGTACGCAGCCCCTTCGAGTACCCACAGTACTACCTGGCTGAGCCATGGCAGTT CTCCATGCTGGCCGCCTACATGTTTCTGCTGATCGTGCTGGGCTTCCCCATCAACT TCCTCACGCTCTACGTCACCGTCCAGCACAAGAAGCTGCGCACGCCTCTCAACTA CATCCTGCTCAACCTAGCCGTGGCTGACCTCTTCATGGTCCTAGGTGGCTTCACC AGCACCCTCTACACCTCTCTGCATGGATACTTCGTCTTCGGGCCCACAGGATGCA ATTTGGAGGGCTTCTTTGCCACCCTGGGCGGTGAAATTGCCCTGTGGTCCTTGGT GGTCCTGGCCATCGAGCGGTACGTGGTGGTGTGTAAGCCCATGAGCAACTTCCGC TTCGGGGAGAACCATGCCATCATGGGCGTTGCCTTCACCTGGGTCATGGCGCTGG CCTGCGCCGCACCCCCACTCGCCGGCTGGTCCAGGTACATCCCCGAGGGCCTGCA GTGCTCGTGTGGAATCGACTACTACACGCTCAAGCCGGAGGTCAACAACGAGTC TTTTGTCATCTACATGTTCGTGGTCCACTTCACCATCCCCATGATTATCATCTTTTT CTGCTATGGGCAGCTCGTCTTCACCGTCAAGGAGGCCGCTGCCCAGCAGCAGGA GTCAGCCACCACACAGAAGGCAGAGAAGGAGGTCACCCGCATGGTCATCATCAT GGTCATCGCTTTCCTGATCTGCTGGGTGCCCTACGCCAGCGTGGCATTCTACATCT TCACCCACCAGGGCTCCAACTTCGGTCCCATCTTCATGACCATCCCAGCGTTCTTT36 / 235B1195.70202WO00#14468377 v2GCCAAGAGCGCCGCCATCTACAACCCTGTCATCTATATCATGATGAACAAGCAGT TCCGGAACTGCATGCTCACCACCATCTGCTGCGGCAAGAACCCACTGGGTGACG ATGAGGCCTCTGCTACCGTGTCCAAGACGGAGACGAGCCAGGTGGCCCCGGCCT AA (SEQ ID NO: 10)

[0139] The sequence of the RHO protein is as follows:MNGTEGPNFYVPFSNATGVVRSPFEYPQYYLAEPWQFSMLAAYMFLLIVLGFPINFL TEYVTVQHKKERTPENYIEENEAVADEFMVEGGFTSTEYTSEHGYFVFGPTGCNEEG FFATEGGEIAEWSEVVEAIERYVVVCKPMSNFRFGENHAIMGVAFTWVMAEACAAP PEAGWSRYIPEGEQCSCGIDYYTEKPEVNNESFVIYMFVVHFTIPMIIIFFCYGQEVFT VKEAAAQQQESATTQKAEKEVTRMVIIMVIAFEICWVPYASVAFYIFTHQGSNFGPIF MTIPAFFAKSAAIYNPVIYIMMNKQFRNCMETTICCGKNPEGDDEASATVSKTETSQ VAPA (SEQ ID NO: 11)Silent mutation

[0140] As used herein, the term “silent mutation” refers to a mutation in a nucleic acid molecule that does not have an effect on the phenotype of the nucleic acid molecule, or the protein it produces if it encodes a protein. Silent mutations can be introduced into coding regions of a nucleic acid (z.e., segments of a gene that encode for a protein), or they can be introduced in non-coding regions of a nucleic acid. A silent mutation in a nucleic acid sequence, e.g., in a target DNA sequence or in a DNA synthesis template sequence to be installed in the target sequence, may be a nucleotide alteration that does not result in expression or function of the amino acid sequence encoded by the nucleic acid sequence, or other functional features of the target nucleic acid sequence. When silent mutations are present in a coding region, they may be synonymous mutations. Synonymous mutations refer to substitutions of one base for another in a gene such that the corresponding amino acid residue of the protein produced by the gene is not modified. This is due to the redundancy of the genetic code, allowing for multiple different codons to encode for the same amino acid in a particular organism. When a silent mutation is in a noncoding region or a junction of a coding region and a non-coding region e.g., an intron / exon junction), it may be in a region that does not impact any biological properties of the nucleic acid molecule (e.g., splicing, gene regulation, RNA lifetime, etc.). In particular embodiments, a silent mutation may also be a “benign” mutation, for example, where a nucleotide substitution results in one or more alterations in the amino acid sequence encoded, but does not result in detrimental impact on the expression or function of the polypeptide. Silent mutations may be useful, for example,37 / 235B1195.70202WO00#14468377 v2for increasing the length of contiguous changes in a desired nucleotide edit or the number of nucleotide edits made to a target nucleotide sequence using prime editing to evade correction of the edit by the MMR pathway as described herein. In certain embodiments, the number of silent mutations installed may be one, or two, or three, or four, or five, or six, or seven, or eight, or nine, or ten, or more. In certain other embodiments involving at least two silent mutations, the silent mutations may be installed within one, or two, or three, or four, or five, or six, or seven, or eight, or nine, or ten, or 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21,22, 23, 24, or 25 nucleotides from the intended edit site.Spacer sequence

[0141] As used herein, the term “spacer sequence” in connection with a guide RNA refers to the portion of the guide RNA that is often, but not always, about 20 nucleotides in length, which contains a nucleotide sequence that shares the same sequence as the protospacer sequence in the target DNA sequence. The spacer sequence anneals to the complement of the protospacer sequence to form a ssRNA / ssDNA hybrid structure at the target site and a corresponding R loop ssDNA structure of the endogenous DNA strand.Subject

[0142] The term “subject,” as used herein, refers to an individual organism, for example, an individual mammal. In some embodiments, the subject is a human. In some embodiments, the subject is a non-human mammal. In some embodiments, the subject is a non-human primate. In some embodiments, the subject is a rodent. In some embodiments, the subject is a sheep, a goat, a cattle, a cat, or a dog. In some embodiments, the subject is a vertebrate, an amphibian, a reptile, a fish, an insect, a fly, or a nematode. In some embodiments, the subject is a research animal. In some embodiments, the subject is genetically engineered, e.g., a genetically engineered non-human subject. The subject may be of either sex, and at any stage of development.Target site

[0143] The term “target site” refers to a sequence within a nucleic acid molecule that is modified e.g., edited) by a prime editor as described herein. The target site further refers to the sequence within a nucleic acid molecule (e.g., a nucleic acid molecule comprising RHO) to which a complex of, for example, a prime editor and a pegRNA binds.Treatment

[0144] The terms “treatment,” “treat,” and “treating,” refer to a clinical intervention aimed to reverse, alleviate, delay the onset of, or inhibit the progress of a disease or disorder (e.g.,38 / 235B1195.70202WO00#14468377 v2retinitis pigmentosa), or one or more symptoms thereof, as described herein. As used herein, the terms “treatment,” “treat,” and “treating” refer to a clinical intervention aimed to reverse, alleviate, delay the onset of, or inhibit the progress of a disease or disorder (e.g., retinitis pigmentosa), or one or more symptoms thereof, as described herein. In some embodiments, treatment may be administered after one or more symptoms have developed and / or after a disease has been diagnosed. In other embodiments, treatment may be administered in the absence of symptoms, e.g., to prevent or delay onset of a symptom or inhibit onset or progression of a disease e.g., retinitis pigmentosa). For example, treatment may be administered to a susceptible individual prior to the onset of symptoms (e.g., in light of a history of symptoms and / or in light of genetic or other susceptibility factors). Treatment may also be continued after symptoms have resolved, for example, to prevent or delay their recurrence.Variant

[0145] As used herein, the term “variant” should be taken to mean the exhibition of qualities that have a pattern that deviates from what occurs in nature, e.g., a variant Cas9 is a Cas9 comprising one or more changes in amino acid residues (i.e., “substitutions”) as compared to a wild type Cas9 amino acid sequence. The term “variant” encompasses homologous proteins having at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity with a reference sequence and having the same or substantially the same functional activity or activities as the reference sequence. The term also encompasses mutants, truncations, or domains of a reference sequence that display the same or substantially the same functional activity or activities as the reference sequence. Vector

[0146] The term “vector,” as used herein, refers to a nucleic acid that can be modified to encode a gene of interest and that is able to enter a host cell, mutate, and replicate within the host cell, and then transfer a replicated form of the vector into another host cell. Exemplary suitable vectors include viral vectors, such as retroviral vectors or bacteriophages and filamentous phage, and conjugative plasmids. Additional suitable vectors will be apparent to those of skill in the art based on the instant disclosure.DETAILED DESCRIPTION OF CERTAIN EMBODIMENTS

[0147] The present disclosure describes the use of prime editors and pegRNAs for editing the RHO gene to correct a P23H mutation in the RHO protein and treat retinitis pigmentosa.39 / 235B1195.70202WO00#14468377 v2Methods of editing RHO (e.g., human RHO) using a prime editor and a pegRNA are provided herein. Such methods may be useful for treating or preventing retinitis pigmentosa. The present disclosure also provides pegRNAs, ngRNAs, systems, complexes, and compositions for editing RHO and treating or preventing retinitis pigmentosa. Polynucleotides, vectors, AAVs, cells, and kits for editing RHO and treating or preventing retinitis pigmentosa are also provided herein.Prime Editing Guide RNAs (pegRNAs)

[0148] The present disclosure provides prime editing guide RNAs (pegRNAs) and nicking guide RNAs (ngRNAs) for prime editing a RHO gene (e.g., a human RHO gene). The pegRNAs and ngRNAs provided herein may be useful for treating or preventing retinitis pigmentosa.

[0149] In some embodiments, the provided pegRNAs target a prime editor to a site in the human RHO gene. In some embodiments, the pegRNAs target a prime editor to a site in the human RHO gene such that the prime editor corrects an A: T base pair to a C: G base pair at nucleotide position 68 in the RHO gene. In some embodiments, the pegRNAs target a prime editor to a site in the human RHO gene such that the prime editor corrects a P23H mutation in a rhodopsin protein encoded by the RHO gene.

[0150] In one aspect, the present disclosure provides pegRNAs comprising an edit template for editing a RHO gene. The edit template installs one or more nucleotide changes into the RHO gene, including correcting an A: T base pair to a C: G base pair at nucleotide position 68 in the RHO gene. In some embodiments, the edit template results in the installation of one or more silent edits in the RHO gene. In certain embodiments, the one or more silent edits comprise one or more PAM-disrupting edits. In certain embodiments, the one or more silent edits comprise one or more MMR pathway-inhibiting edits. In certain embodiments, the one or more silent edits include changing a C: G base pair to a T: A base pair at nucleotide position 66 in the RHO gene. In certain embodiments, the one or more silent edits include changing a C: G base pair to a G: C base pair at nucleotide position 69 in the RHO gene. In some embodiments, the pegRNA comprises an edit template of 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, or 25 nucleotides in length. In some embodiments, the pegRNA comprises an edit template comprising a sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identical to, or 100% identical to, or comprising one, two, three, four, or five mutations relative to, the40 / 235B1195.70202WO00#14468377 v2sequence CAGTCCTTT, CGCAGTCCTTT (SEQ ID NO: 12), TACGCAGTCCTTT (SEQ ID NO: 13), GGTACGCAGTCCTTT (SEQ ID NO: 14), GTGGTACGCAGTCCTTT (SEQ ID NO: 15), GTGTGGTACGCAGTCCTTT (SEQ ID NO: 16), CTCTCCTTT, CGCTCTCCTTT (SEQ ID NO: 17), TACGCGCTCTCCTTT (SEQ ID NO: 18), GGTACGCTCTCCTTT (SEQ ID NO: 19), GTGGTACGCTCTCCTTT (SEQ ID NO: 20), GTGTGGTACGCTCTCCTTT (SEQ ID NO: 21), GCAGTCCGT, CGCAGTCCGT (SEQ ID NO: 22), CGCTCTCCGT (SEQ ID NO: 23), ACGCAGTCCGT (SEQ ID NO: 24), ACGCTCTCCGT (SEQ ID NO: 25), TACGCAGTCCGT (SEQ ID NO: 26), TACGCTCTCCGT (SEQ ID NO: 27), GTACGCAGTCCGT (SEQ ID NO: 28), GTACGCTCTCCGT (SEQ ID NO: 29), GGTACGCAGTCCGT (SEQ ID NO: 30), GGTACGCTCTCCGT (SEQ ID NO: 31), GTGGTACGCAGTCCGT (SEQ ID NO: 32), GTGGTACGCTCTCCGT (SEQ ID NO: 33), GTGTGGTACGCAGTCCGT (SEQ ID NO: 34), GTGTGGTACGCTCTCCGT (SEQ ID NO: 35), TGTGGTACGCAGTCCTTT (SEQ ID NO: 36), GGTGTGGTACGCAGTCCTTT (SEQ ID NO: 37), GGGTGTGGTACGCAGTCCTTT (SEQ ID NO: 38), CGGGTGTGGTACGCAGTCCTTT (SEQ ID NO: 39), ACGGGTGTGGTACGCAGTCCTTT (SEQ ID NO: 40), GGTGTGGTACGCAGCCCCTT (SEQ ID NO: 41), GGTGTGGTACGCAGTCCCTT (SEQ ID NO: 42), GGTGTGGTACGCTCTCCCTT (SEQ ID NO: 43), GGTGTGGTACGCTCCCCCTT (SEQ ID NO: 44), GGTGTGGTACGCTCACCCTT (SEQ ID NO: 45), GGTGTGGTACGCTCGCCCTT (SEQ ID NO: 46), GGTGTGGTACGGAGCCCCTT (SEQ ID NO: 47), GGTGTGGTACGGAGTCCCTT (SEQ ID NO: 48), GGTGTGGTACGGTCTCCCTT (SEQ ID NO: 49), GGTGTGGTACGGTCCCCCTT (SEQ ID NO: 50), GGTGTGGTACGGTCACCCTT (SEQ ID NO: 51), GGTGTGGTACGGTCGCCCTT (SEQ ID NO: 52), GGTGTGGTACGCAGCCCGTT (SEQ ID NO: 53), GGTGTGGTACGCAGTCCGTT (SEQ ID NO: 54), GGTGTGGTACGCTCTCCGTT (SEQ ID NO: 55), GGTGTGGTACGCTCCCCGTT (SEQ ID NO: 56), GGTGTGGTACGCTCACCGTT (SEQ ID NO: 57), GGTGTGGTACGCTCGCCGTT (SEQ ID NO: 58), GGTGTGGTACGGAGCCCGTT (SEQ ID NO: 59), GGTGTGGTACGGAGTCCGTT (SEQ ID NO: 60), GGTGTGGTACGGTCTCCGTT (SEQ ID NO: 61), GGTGTGGTACGGTCCCCGTT (SEQ ID NO: 62), GGTGTGGTACGGTCACCGTT (SEQ ID NO: 63), GGTGTGGTACGGTCGCCGTT (SEQ ID NO: 64), GGTGTGGTACGCAGCCCATT (SEQ ID NO: 65), GGTGTGGTACGCAGTCCATT (SEQ41 / 235B1195.70202WO00#14468377 v2ID NO: 66), GGTGTGGTACGCTCTCCATT (SEQ ID NO: 67), GGTGTGGTACGCTCCCCATT (SEQ ID NO: 68), GGTGTGGTACGCTCACCATT (SEQ ID NO: 69), GGTGTGGTACGCTCGCCATT (SEQ ID NO: 70), GGTGTGGTACGGAGCCCATT (SEQ ID NO: 71), GGTGTGGTACGGAGTCCATT (SEQ ID NO: 72), GGTGTGGTACGGTCTCCATT (SEQ ID NO: 73), GGTGTGGTACGGTCCCCATT (SEQ ID NO: 74), GGTGTGGTACGGTCACCATT (SEQ ID NO: 75), GGTGTGGTACGGTCGCCATT (SEQ ID NO: 76), GGTGTGGTACGCAGCCCTTT (SEQ ID NO: 77), GGTGTGGTACGCTCTCCTTT (SEQ ID NO: 78), GGTGTGGTACGCTCCCCTTT (SEQ ID NO: 79), GGTGTGGTACGCTCACCTTT (SEQ ID NO: 80), GGTGTGGTACGCTCGCCTTT (SEQ ID NO: 81), GGTGTGGTACGGAGCCCTTT (SEQ ID NO: 82), GGTGTGGTACGGAGTCCTTT (SEQ ID NO: 83), GGTGTGGTACGGTCTCCTTT (SEQ ID NO: 84), GGTGTGGTACGGTCCCCTTT (SEQ ID NO: 85), GGTGTGGTACGGTCACCTTT (SEQ ID NO: 86), GGTGTGGTACGGTCGCCTTT (SEQ ID NO: 87), CGGGTGTGGTACGCAGCCCCTT (SEQ ID NO: 88), CGGGTGTGGTACGCAGTCCCTT (SEQ ID NO: 89), CGGGTGTGGTACGCTCTCCCTT (SEQ ID NO: 90), CGGGTGTGGTACGCTCCCCCTT (SEQ ID NO: 91), CGGGTGTGGTACGCTCACCCTT (SEQ ID NO: 92), CGGGTGTGGTACGCTCGCCCTT (SEQ ID NO: 93), CGGGTGTGGTACGGAGCCCCTT (SEQ ID NO: 94), CGGGTGTGGTACGGAGTCCCTT (SEQ ID NO: 95), CGGGTGTGGTACGGTCTCCCTT (SEQ ID NO: 96), CGGGTGTGGTACGGTCCCCCTT (SEQ ID NO: 97), CGGGTGTGGTACGGTCACCCTT (SEQ ID NO: 98), CGGGTGTGGTACGGTCGCCCTT (SEQ ID NO: 99), CGGGTGTGGTACGCAGCCCGTT (SEQ ID NO: 100), CGGGTGTGGTACGCAGTCCGTT (SEQ ID NO: 101), CGGGTGTGGTACGCTCTCCGTT (SEQ ID NO: 102), CGGGTGTGGTACGCTCCCCGTT (SEQ ID NO: 103), CGGGTGTGGTACGCTCACCGTT (SEQ ID NO: 104), CGGGTGTGGTACGCTCGCCGTT (SEQ ID NO: 105), CGGGTGTGGTACGGAGCCCGTT (SEQ ID NO: 106), CGGGTGTGGTACGGAGTCCGTT (SEQ ID NO: 107), CGGGTGTGGTACGGTCTCCGTT (SEQ ID NO: 108), CGGGTGTGGTACGGTCCCCGTT (SEQ ID NO: 109), CGGGTGTGGTACGGTCACCGTT (SEQ ID NO: 110),42 / 235B1195.70202WO00#14468377 v2CGGGTGTGGTACGGTCGCCGTT (SEQ ID NO: 111), CGGGTGTGGTACGCAGCCCATT (SEQ ID NO: 112), CGGGTGTGGTACGCAGTCCATT (SEQ ID NO: 113), CGGGTGTGGTACGCTCTCCATT (SEQ ID NO: 114), CGGGTGTGGTACGCTCCCCATT (SEQ ID NO: 115), CGGGTGTGGTACGCTCACCATT (SEQ ID NO: 116), CGGGTGTGGTACGCTCGCCATT (SEQ ID NO: 117), CGGGTGTGGTACGGAGCCCATT (SEQ ID NO: 118), CGGGTGTGGTACGGAGTCCATT (SEQ ID NO: 119), CGGGTGTGGTACGGTCTCCATT (SEQ ID NO: 120), CGGGTGTGGTACGGTCCCCATT (SEQ ID NO: 121), CGGGTGTGGTACGGTCACCATT (SEQ ID NO: 122), CGGGTGTGGTACGGTCGCCATT (SEQ ID NO: 123), CGGGTGTGGTACGCAGCCCTTT (SEQ ID NO: 124), CGGGTGTGGTACGCTCTCCTTT (SEQ ID NO: 125), CGGGTGTGGTACGCTCCCCTTT (SEQ ID NO: 126), CGGGTGTGGTACGCTCACCTTT (SEQ ID NO: 127), CGGGTGTGGTACGCTCGCCTTT (SEQ ID NO: 128), CGGGTGTGGTACGGAGCCCTTT (SEQ ID NO: 129), CGGGTGTGGTACGGAGTCCTTT (SEQ ID NO: 130), CGGGTGTGGTACGGTCTCCTTT (SEQ ID NO: 131), CGGGTGTGGTACGGTCCCCTTT (SEQ ID NO: 132), CGGGTGTGGTACGGTCACCTTT (SEQ ID NO: 133), CGGGTGTGGTACGGTCGCCTTT (SEQ ID NO: 134), GGGTGTGGTACGCAGCCCCTT (SEQ ID NO: 135), GGGTGTGGTACGCAGTCCCTT (SEQ ID NO: 136), GGGTGTGGTACGCTCTCCCTT (SEQ ID NO: 137), GGGTGTGGTACGCTCCCCCTT (SEQ ID NO: 138), GGGTGTGGTACGCTCACCCTT (SEQ ID NO: 139), GGGTGTGGTACGCTCGCCCTT (SEQ ID NO: 140), GGGTGTGGTACGGAGCCCCTT (SEQ ID NO: 141), GGGTGTGGTACGGAGTCCCTT (SEQ ID NO: 142), GGGTGTGGTACGGTCTCCCTT (SEQ ID NO: 143), GGGTGTGGTACGGTCCCCCTT (SEQ ID NO: 144), GGGTGTGGTACGGTCACCCTT (SEQ ID NO: 145), GGGTGTGGTACGGTCGCCCTT (SEQ ID NO: 146), GGGTGTGGTACGCAGCCCGTT (SEQ ID NO: 147), GGGTGTGGTACGCAGTCCGTT (SEQ ID NO: 148),43 / 235B1195.70202WO00#14468377 v2GGGTGTGGTACGCTCTCCGTT (SEQ ID NO: 149), GGGTGTGGTACGCTCCCCGTT (SEQ ID NO: 150), GGGTGTGGTACGCTCACCGTT (SEQ ID NO: 151), GGGTGTGGTACGCTCGCCGTT (SEQ ID NO: 152), GGGTGTGGTACGGAGCCCGTT (SEQ ID NO: 153), GGGTGTGGTACGGAGTCCGTT (SEQ ID NO: 154), GGGTGTGGTACGGTCTCCGTT (SEQ ID NO: 155), GGGTGTGGTACGGTCCCCGTT (SEQ ID NO: 156), GGGTGTGGTACGGTCACCGTT (SEQ ID NO: 157), GGGTGTGGTACGGTCGCCGTT (SEQ ID NO: 158), GGGTGTGGTACGCAGCCCATT (SEQ ID NO: 159), GGGTGTGGTACGCAGTCCATT (SEQ ID NO: 160), GGGTGTGGTACGCTCTCCATT (SEQ ID NO: 161), GGGTGTGGTACGCTCCCCATT (SEQ ID NO: 162), GGGTGTGGTACGCTCACCATT (SEQ ID NO: 163), GGGTGTGGTACGCTCGCCATT (SEQ ID NO: 164), GGGTGTGGTACGGAGCCCATT (SEQ ID NO: 165), GGGTGTGGTACGGAGTCCATT (SEQ ID NO: 166), GGGTGTGGTACGGTCTCCATT (SEQ ID NO: 167), GGGTGTGGTACGGTCCCCATT (SEQ ID NO: 168), GGGTGTGGTACGGTCACCATT (SEQ ID NO: 169), GGGTGTGGTACGGTCGCCATT (SEQ ID NO: 170), GGGTGTGGTACGCAGCCCTTT (SEQ ID NO: 171), GGGTGTGGTACGCTCTCCTTT (SEQ ID NO: 172), GGGTGTGGTACGCTCCCCTTT (SEQ ID NO: 173), GGGTGTGGTACGCTCACCTTT (SEQ ID NO: 174), GGGTGTGGTACGCTCGCCTTT (SEQ ID NO: 175), GGGTGTGGTACGGAGCCCTTT (SEQ ID NO: 176), GGGTGTGGTACGGAGTCCTTT (SEQ ID NO: 177), GGGTGTGGTACGGTCTCCTTT (SEQ ID NO: 178), GGGTGTGGTACGGTCCCCTTT (SEQ ID NO: 179), GGGTGTGGTACGGTCACCTTT (SEQ ID NO: 180), GGGTGTGGTACGGTCGCCTTT (SEQ ID NO: 181), ACGGGTGTGGTACGCAGTCCGTT (SEQ ID NO: 182), or GACGGGTGTGGTACGCAGTCCGTT (SEQ ID NO: 183). In certain embodiments, the pegRNA comprises an edit template comprising a sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to, or comprising one, two, three, four, or five mutations relative to, the sequence GGGTGTGGTACGGAGTCCGTT (SEQ ID NO: 148).

[0151] The pegRNAs of the present disclosure also comprise a spacer sequence to target a prime editor to a particular protospacer sequence in the RHO gene, e.g., a protospacer sequence that comprises nucleotide position 68 in the human RHO gene. In some embodiments, the pegRNA comprises a spacer sequence 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48,44 / 235B1195.70202WO00#14468377 v249, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, or 150 nucleotides in length. In some embodiments, the pegRNA comprises a spacer comprising a sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to, or comprising one, two, three, four, or five mutations relative to, the sequence:GTAGTACTGTGGGTACTCGA (SEQ ID NO: 185), GTACTGTGGGTACTCGAAG (SEQ ID NO: 186), AGTACTGTGGGTACTCGAAG (SEQ ID NO: 187), GTACTGTGGGTACTCGAAGT (SEQ ID NO: 188), GGTACTGTGGGTACTCGAAG (SEQ ID NO: 189), GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT ACGCAGTCCATTCGAGTACCCACAGT (SEQ ID NO: 190), GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT ACGCAGTCCATTCGAGTACCCACAG (SEQ ID NO: 191), GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGG TGTGGTACGGTCGCCATTCGAGTACCCACAGT (SEQ ID NO: 192), GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGG TGTGGTACGGTCGCCATTCGAGTACCCACAG (SEQ ID NO: 193), GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGG TGTGGTACGGTCGCCATTCGAGTACCCACA (SEQ ID NO: 194), GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGG TGTGGTACGTTCGCCATTCGAGTACCCACAGT (SEQ ID NO: 195), GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGAC45 / 235B1195.70202WO00#14468377 v2GGGTGTGGTACGTTCGCCATTCGAGTACCCACAGT (SEQ ID NO: 196), GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGG TGTGGTACGTTCGCCATTCGAGTACCCACAG (SEQ ID NO: 197), GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGG TGTGGTACGGTCTCCATTCGAGTACCCACAGT (SEQ ID NO: 198), GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGG TGTGGTACGGTCTCCATTCGAGTACCCACAG (SEQ ID NO: 199), GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT ACGCAGTCCCTTCGAGTACCCACAGT (SEQ ID NO: 200), GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGG TGTGGTACGGTCTCCATTCGAGTACCCACA (SEQ ID NO: 201), GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT ACGCAGTCCCTTCGAGTACCCACAG (SEQ ID NO: 202), GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT ACGCAGTCCCTTCGAGTACCCACA (SEQ ID NO: 203), GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGAC GGGTGTGGTACGTTCTCCATTCGAGTACCCACAGT (SEQ ID NO: 204), GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGAC GGGTGTGGTACGTTCTCCATTCGAGTACCCACAG (SEQ ID NO: 205), GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGAC GGGTGTGGTACGTTCTCCATTCGAGTACCCACA (SEQ ID NO: 206), GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGG46 / 235B1195.70202WO00#14468377 v2TGTGGTACGTTCGCCTTTCGAGTACCCACAGT (SEQ ID NO: 207), GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT ACGCAGTCCGTTCGAGTACCCACAGT (SEQ ID NO: 208), GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGG TGTGGTACGTTCGCCTTTCGAGTACCCACAG (SEQ ID NO: 209), GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT ACGCAGTCCGTTCGAGTACCCACAG (SEQ ID NO: 210), GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGG TGTGGTACGTTCGCCTTTCGAGTACCCACA (SEQ ID NO: 211), GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT ACGCAGTCCGTTCGAGTACCCACA (SEQ ID NO: 212), GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGG TGTGGTACGATCGCCATTCGAGTACCCACAGT (SEQ ID NO: 213), GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGG TGTGGTACGCTCGCCTTTCGAGTACCCACAGT (SEQ ID NO: 214), GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGG TGTGGTACGATCGCCTTTCGAGTACCCACAGT (SEQ ID NO: 215), GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGCG ACGGGTGTGGTACGCTCGCCGTTCGAGTACCCACAGT (SEQ ID NO: 216), GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGAC GGGTGTGGTACGATCTCCATTCGAGTACCCACAGT (SEQ ID NO: 217), GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGG47 / 235B1195.70202WO00#14468377 v2TGTGGTACGGTCGCCTTTCGAGTACCCACAGT (SEQ ID NO: 218), GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGCG ACGGGTGTGGTACGGTCGCCGTTCGAGTACCCACAGT (SEQ ID NO: 219), GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGAC GGGTGTGGTACGTTCGCCGTTCGAGTACCCACAGT (SEQ ID NO: 220), GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGAC GGGTGTGGTACGATCGCCGTTCGAGTACCCACAGT (SEQ ID NO: 221), GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGG TGTGGTACGGTCACCATTCGAGTACCCACAGT (SEQ ID NO: 222), GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT ACGCAGTCCTTTCGAGTACCCACAGT (SEQ ID NO: 223), GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGG TGTGGTACGTTCACCATTCGAGTACCCACAGT (SEQ ID NO: 224), GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCAAT GCGACGGGTGTGGTGCGATCGCCATTCGAGTACCCACAGT (SEQ ID NO: 225), GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGG TGTGGTACGGTCACCCTTCGAGTACCCACAGT (SEQ ID NO: 226), GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGG TGTGGTACGATCACCATTCGAGTACCCACAGT (SEQ ID NO: 227), GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGG TGTGGTACGCTCTCCATTCGAGTACCCACAGT (SEQ ID NO: 228), GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT48 / 235B1195.70202WO00#14468377 v2GTGGTACGCTCACCATTCGAGTACCCACAGT (SEQ ID NO: 229), GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCAAT GCGACGGGTGTGGTACGATCACCCTTCGAGTACCCACAGT (SEQ ID NO: 230), GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCAAT GCGACGGGTGTGGTGCGCTCGCCGTTCGAGTACCCACAGT (SEQ ID NO: 231), GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCAAT GCGACGGGTGTGGTGCGCTCGCCATTCGAGTACCCACAGT (SEQ ID NO: 232), GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT GTGGTACGCTCGCCATTCGAGTACCCACAGT (SEQ ID NO: 233), GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCAAT GCGACGGGTGTGGTGCGCTCGCCCTTCGAGTACCCACAGT (SEQ ID NO: 234), GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCAAT GCGACGGGTGTGGTGCGTTCGCCATTCGAGTACCCACAGT (SEQ ID NO: 235), GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGG TGTGGTACGCTCACCCTTCGAGTACCCACAGT (SEQ ID NO: 236), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG TACGCAGTCCATTCGAGTACCCACAGT (SEQ ID NO: 237), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG TACGCAGTCCATTCGAGTACCCACAG (SEQ ID NO: 238), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG TACGCAGTCCATTCGAGTACCCACA (SEQ ID NO: 239), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG49 / 235B1195.70202WO00#14468377 v2GTGTGGTACGGTCGCCATTCGAGTACCCACAGT (SEQ ID NO: 240), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGGTCGCCATTCGAGTACCCACAG (SEQ ID NO: 241), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGGTCGCCATTCGAGTACCCACA (SEQ ID NO: 242), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGTTCGCCATTCGAGTACCCACAGT (SEQ ID NO: 243), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGA CGGGTGTGGTACGTTCGCCATTCGAGTACCCACAGT (SEQ ID NO: 244), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGTTCGCCATTCGAGTACCCACAG (SEQ ID NO: 245), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGGTCTCCATTCGAGTACCCACAGT (SEQ ID NO: 246), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGGTCTCCATTCGAGTACCCACAG (SEQ ID NO: 247), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG TACGCAGTCCCTTCGAGTACCCACAGT (SEQ ID NO: 248), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGGTCTCCATTCGAGTACCCACA (SEQ ID NO: 249), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG TACGCAGTCCCTTCGAGTACCCACAG (SEQ ID NO: 250), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG50 / 235B1195.70202WO00#14468377 v2TACGCAGTCCCTTCGAGTACCCACA (SEQ ID NO: 251), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGA CGGGTGTGGTACGTTCTCCATTCGAGTACCCACAGT (SEQ ID NO: 252), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGA CGGGTGTGGTACGTTCTCCATTCGAGTACCCACAG (SEQ ID NO: 253), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGA CGGGTGTGGTACGTTCTCCATTCGAGTACCCACA (SEQ ID NO: 254), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGTTCGCCTTTCGAGTACCCACAGT (SEQ ID NO: 255), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG TACGCAGTCCGTTCGAGTACCCACAGT (SEQ ID NO: 256), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGTTCGCCTTTCGAGTACCCACAG (SEQ ID NO: 257), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG TACGCAGTCCGTTCGAGTACCCACAG (SEQ ID NO: 258), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGTTCGCCTTTCGAGTACCCACA (SEQ ID NO: 259), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG TACGCAGTCCCTTCGAGTACCCACA (SEQ ID NO: 260), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGATCGCCATTCGAGTACCCACAGT (SEQ ID NO: 261), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG51 / 235B1195.70202WO00#14468377 v2GTGTGGTACGCTCGCCTTTCGAGTACCCACAGT (SEQ ID NO: 262), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGATCGCCTTTCGAGTACCCACAGT (SEQ ID NO: 263), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGC GACGGGTGTGGTACGCTCGCCGTTCGAGTACCCACAGT (SEQ ID NO: 264), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGA CGGGTGTGGTACGATCTCCATTCGAGTACCCACAGT (SEQ ID NO: 265), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGGTCGCCTTTCGAGTACCCACAGT (SEQ ID NO: 266), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGC GACGGGTGTGGTACGGTCGCCGTTCGAGTACCCACAGT (SEQ ID NO: 267), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGA CGGGTGTGGTACGTTCGCCGTTCGAGTACCCACAGT (SEQ ID NO: 268), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGA CGGGTGTGGTACGATCGCCGTTCGAGTACCCACAGT (SEQ ID NO: 269), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGGTCACCATTCGAGTACCCACAGT (SEQ ID NO: 270), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG TACGCAGTCCTTTCGAGTACCCACAGT (SEQ ID NO: 271), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGTTCACCATTCGAGTACCCACAGT (SEQ ID NO: 272), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCAA52 / 235B1195.70202WO00#14468377 v2TGCGACGGGTGTGGTGCGATCGCCATTCGAGTACCCACAGT (SEQ ID NO: 273), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGGTCACCCTTCGAGTACCCACAGT (SEQ ID NO: 274), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGATCACCATTCGAGTACCCACAGT (SEQ ID NO: 275), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGCTCTCCATTCGAGTACCCACAGT (SEQ ID NO: 276), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG TGTGGTACGCTCACCATTCGAGTACCCACAGT (SEQ ID NO: 277), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCAA TGCGACGGGTGTGGTACGATCACCCTTCGAGTACCCACAGT (SEQ ID NO: 278), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCAA TGCGACGGGTGTGGTGCGCTCGCCGTTCGAGTACCCACAGT (SEQ ID NO: 279), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCAA TGCGACGGGTGTGGTGCGCTCGCCATTCGAGTACCCACAGT (SEQ ID NO: 280), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG TGTGGTACGCTCGCCATTCGAGTACCCACAGT (SEQ ID NO: 281), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCAA TGCGACGGGTGTGGTGCGCTCGCCCTTCGAGTACCCACAGT (SEQ ID NO: 282), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCAA TGCGACGGGTGTGGTGCGTTCGCCATTCGAGTACCCACAGT (SEQ ID NO: 283), or GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG53 / 235B1195.70202WO00#14468377 v2GTGTGGTACGCTCACCCTTCGAGTACCCACAGT. (SEQ ID NO: 284). In certain embodiments, the pegRNA comprises a spacer comprising a sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to, or comprising one, two, three, four, or five mutations relative to, the sequence: GGTACTGTGGGTACTCGAAG (SEQ ID NO: 189).

[0152] The pegRNAs provided herein also comprise a backbone scaffold sequence that facilitates binding of the pegRNA to a napDNAbp, for example, a Cas9 protein (e.g., a Cas9 protein as part of a prime editor). In some embodiments, the provided pegRNAs comprise a backbone scaffold sequence for binding to SpCas9. In some embodiments, the pegRNA comprises a backbone scaffold comprising a sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to, or comprising one, two, three, four, or five mutations relative to, the sequence:GTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTTTAAATAAGGCTAGTCCGTTA TCAACTTGAAAAAGTGGCACCGAGTCGGTGC (SEQ ID NO: 285), GTTTGAGAGCTATGCTGGAAACAGCATAGCAAGTTCAAATAAGGCTAGTCCGTT ATCAACTTGAAAAAGTGGCACCGAGTCGGTGC (SEQ ID NO: 286), or GTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTTGAAATAAGGCTAGTCCGTT ATCAACTTGAAAAAGTGGCACCGAGTCGGTGC (SEQ ID NO: 287). In certain embodiments, the pegRNA comprises a backbone scaffold comprising a sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to, or comprising one, two, three, four, or five mutations relative to, the sequence:GTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTTTAAATAAGGCTAGTCCGTTA TCAACTTGAAAAAGTGGCACCGAGTCGGTGC (SEQ ID NO: 285).

[0153] The pegRNAs provided herein also comprise a primer binding site (PBS). In some embodiments, the PBS is about 5, about 6, about 7, about 8, about 9, about 10, about 11, about 12, about 13, about 14, or about 15 nucleotides in length. In some embodiments, the pegRNA comprises a PBS comprising a sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to, or comprising one, two, three, four, or five mutations relative to, the sequence:AGTACCCACAGT (SEQ ID NO: 288), CGAGTACCC, CGAGTACCCAC (SEQ ID NO: 289), CGAGTACCCACAG (SEQ ID NO: 290), CGAGTACCCACAGTA (SEQ ID NO: 291), TCGAGTACC, TCGAGTACCC (SEQ ID NO: 292), TCGAGTACCCA (SEQ ID NO:54 / 235B1195.70202WO00#14468377 v2293), TCGAGTACCCAC (SEQ ID NO: 294), TCGAGTACCCACA (SEQ ID NO: 295), TCGAGTACCCACAG (SEQ ID NO: 296), CGAGTACC, or CGAGTACCCA (SEQ ID NO: 297). In certain embodiments, the pegRNA comprises a PBS comprising a sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to, or comprising one, two, three, four, or five mutations relative to, the sequence CGAGTACC. In certain embodiments, the pegRNA comprises a PBS comprising a sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to, or comprising one, two, three, four, or five mutations relative to, the sequence: CGAGTACCC.

[0154] In some embodiments, the pegRNAs provided herein further comprise a structured motif at the 3 ' end. In some embodiments, the structured motif is a toe-loop, a hairpin, a stem-loop, a pseudoknot, an aptamer, a G-quadraplex, a tRNA, a riboswitch, or a ribozyme. In certain embodiments, the structured motif is an RNA pseudoknot motif. In some embodiments, the structured motif comprises a sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to, or comprising one, two, three, four, or five mutations relative to, the sequence:CGCGGTTCTATCTAGTTACGCGTTAAACCAACTAGAA (SEQ ID NO: 298), CCGCCATGTCCCTGGCGTTAAAGGGAA (SEQ ID NO: 299), CGCGGTTCGATCTAGTTACGCGTTAAACCAACTAGAA (SEQ ID NO: 300), ACGTCGTGCCGTACGGTAAACGGCACA (SEQ ID NO: 301), CGAGGGTGCGGTTGGCCTCGTAAAAAGCCGCA (SEQ ID NO: 302), AGTCCATGGTGAGGGGACTTGATACCTCACCG (SEQ ID NO: 303), CGTCGGTTCTACCTAGTTACGACGTTAAACCAACTAGGA (SEQ ID NO: 1295), AGGCCATGGTGAGGGGCCTGATACCTCACCG (SEQ ID NO: 1296), CCGCCTTGTCCCGGGCGTTAAAGGGAA (SEQ ID NO: 1297), CCCAGACCTTGAGGGTGGTCTGGTCAATAAAAACCCTCC (SEQ ID NO: 1298), CCTTCGCGTCGGAAGTAAAACGACC (SEQ ID NO: 1299), ACGGTCGTGCAGTCATCGGTAAGACTGCACA (SEQ ID NO: 1300), AAGTCCATGGTGAGGGGACTTGATACCTCACCG (SEQ ID NO: 1301), CCCAGCCTTGGGGTGGCTGGTCAATAAAAACCCCC (SEQ ID NO: 1302), CCTTCGCTCGGAAGTAAAACGAC (SEQ ID NO: 1303), ACGTCGTGCAGTACGGTAAACTGCACA (SEQ ID NO: 1304), CCGCCTGTCCCGGCGTTAAAGGGAA (SEQ ID NO: 1305),55 / 235B1195.70202WO00#14468377 v2CGAGGGGCGGTTGGCCTCGTAAAAAGCCGC (SEQID NO: 1306), GCCGGGCGCGGTGGCGCGTGCCTGTAGTCCCAGCTACTCGGGAGGCT (SEQ ID NO: 1307), CCCGCCCCCCGTCGGTTAACGGGA (SEQ ID NO: 1308), ACGCGGGTGCTGCGATAGTGCCA (SEQ ID NO: 1309), CGTGGTTCCATCTAGTTACACGTTAAACCAACTAGAA (SEQ ID NO: 1310), AACGTCCATGGTGAGGGGACGTTGATACCTCACCG (SEQID NO: 1311), ACGTCGTCCAGTACGGTAAACTGGACA (SEQ ID NO: 1312), ACGTCGTGCACGTACGGTAAACGTGCACA (SEQ ID NO: 1313), CGTCGGTTCTACCTAGTTACGACGTTAAACCAACTAGGAAAAAAAGTCCATGGTG AGGGGACTTGATACCTCACCG (SEQ ID NO: 1314), AAGTCCATGGTGAGGGGACTTGATACCTCACCGAAAACGTCGGTTCTACCTAGTT ACGACGTTAAACCAACTAGGA (SEQ ID NO: 1315), CCGCCATGTCCCTGGCGTTAAAGGGAAAAAAACGGTCGTGCAGTCATCGGTAAG ACTGCACA (SEQ ID NO: 1316), ACGGTCGTGCAGTCATCGGTAAGACTGCACAAAAACCGCCATGTCCCTGGCGTTA AAGGGAA (SEQ ID NO: 1317), AGCGGTTCTATCTACTTACGCGTTAAACCAACTAGAA (SEQ ID NO: 1318), or TTTGCGTCCAAGTCAGAGTCAACCTATAACCTTAAGA (SEQ ID NO: 1319). In certain embodiments, the structured motif comprises a sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to, or comprising one, two, three, four, or five mutations relative to, the sequence CGCGGTTCTATCTAGTTACGCGTTAAACCAACTAGAA (SEQ ID NO: 298). In certain embodiments, the structured motif comprises a sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to, or comprising one, two, three, four, or five mutations relative to, the sequence:CGAGGGTGCGGTTGGCCTCGTAAAAAGCCGCA (SEQ ID NO: 302). In certain embodiments, the structured motif comprises a sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to, or comprising one, two, three, four, or five mutations relative to, the sequence ACGTCGTGCCGTACGGTAAACGGCACA (SEQ ID NO: 301). In certain embodiments, the structured motif comprises a sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to, or comprising one, two, three, four, or five mutations relative to, the sequence56 / 235B1195.70202WO00#14468377 v2AAGTCCATGGTGAGGGGACTTGATACCTCACCG (SEQ ID NO: 1301). In certain embodiments, the structured motif comprises a sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to, or comprising one, two, three, four, or five mutations relative to, the sequence GCCGGGCGCGGTGGCGCGTGCCTGTAGTCCCAGCTACTCGGGAGGCT (SEQ ID NO: 1307).

[0155] In some embodiments, the pegRNAs provided herein further comprise an optional linker joining the structured motif to the 3' end of the pegRNA. In some embodiments, the linker is a nucleic acid linker. In some embodiments, the linker is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 nucleotides in length. In certain embodiments, the linker is 8 nucleotides in length. In some embodiments, the linker comprises a sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to, or comprising one, two, three, four, or five mutations relative to, the sequence: TGAAAGTC, AAATTAAC, TGCCCAAC, TGCCATCC, TGATCCCT, TTCTCTCA, TGATCCAA, TAACCAAT, TGATCCAC, TATTTAAA, TTTCCTCA, TTCCTCTA, TTCTCCTC, AAAGGATA, CAATTAAT, CATTAAGC, TCCCTTCC, TCCTGAAT, TCCTTAAT, CCAATATC, CTTCCTCT, CCAATTCC, TCCCTTCT, TCAAATCT, TCCTAAAT, AAAGATAA, AAAGAATG, AAAGAATA, CTTCCCAT, CCTGTTCA, GAGAATAG, GAGAACCT, CCTCCATT, CAGAGAAT, CCTCCGAA, CCTAAAGG, CTTAGTAA, AATATAAC, AATAAGTC, ATATAAAC, ATCATAAT, GAAAGAAG, ATCAGATA, ATAATAAT, GATTAATA, GATCCATA, ATTCCGAC, GAGAAGAA, GGATAATC, AATTAATA, TAATAATG, TAATAAAC, TTTCCGAC, TTCTCCAC, TGAATCCA, TAATAATA, TTCCATCA, TGATCATA, TTCCTCCT, TGATCCAT, TTCTCCGA, AAAGGATT, CAATAATA, CACCTATC, CCTTTCGA, CCTTTAAC, TCCAAGAG, CAATCAAC, TAATAGAA, CCAATCCA, TTCCAAAT, TCCAATCC, TTCAAATT, CAAGGAGA, AAGAGAAA, AAAGATTT, CGAGAAAT, CCGTCCGA, CGAAGAAG, GAGGACCA, AAGAAATA, AGAAGATC, AAGAAGAA, CCGGAGAC, CCGTTCAT, AATAATTT, AGATAAAT, AAGATCCA, AGAAGAAT, AGAAGAAG, AGGAATGA, AATAAATT, AGATCCCT, AATTCAAT, AATATTTC, AGAAGTAT, GGGCTACC, TAATAATT, GGATTAAA, CACTGTAG, ACCATTAG, CCATTTAG, GTTAACCA, TTCTAAAC, ATTTCCAT, CCTTAAAG, CCCAAGAT, GAGTTCAA, GTGTCCCA, TGATAAAC, ATAATTTA, CCTGTCTA, AGATCCTT, TAATCCCT, AATAATCC, CTTCCTTA, AATTAATG, CCTTCAAA, AAATAAAG, TGTTCAAC,57 / 235B1195.70202WO00#14468377 v2AATAAAGA, CGCCTAAT, AACTGTTA, CCATCCAC, ATCCATTT, CCAAATTT, ATTTAATC, CCTTCCAC, GGATATCC, TGTCCAAG, GCGCCCTC, CACCTGTA, ACCATTAA, CCATATCT, AATCTAAT, TAAATCTG, AACCTTCT, CCTTTAAT, ATTAATTC, CCAAATCG, ATTTCCTA, TAATCCTT, AATCAATC, CTTCCCGC, CCCTTTCT, CCTTCTAA, GTCTATCC, TGATAAAG, AATGAATA, CTTTAAAG, CCCTTAGC, CCAAGAAT, AAATTTCA, TGAATCCT, AATCCTAT, CCATTCCT, CCTTAATC, AATCTCTT, TGATCCTC, ATTAAATA, TTCAATTC, ATTAAGAA, CCTAGAAA, AAATCCTA, TTCCTAAA, ATCTCTCT, TTCCTTAA, ATTTCCGC, GTTTAAAC, AATTTAAC, TCATTTCA, CAAATTAG, GAATTTAA, GTTAAATC, TTCCTAAC, ATCCTTAA, TCCCTGAG, AATAGAGG, CCTGATAT, GTTAAACC, TTCCCTTC, AATCTTCG, TCCCTGAT, ATTTCCCT, CCTTAGAC, GTTAACCG, GTCTCCTC, GTCTCCCT, AAATTAAT, TTCTAATC, TTTCCTAA, TGATTCAA, TGAATTCC, TTCCCATA, ATCCAAAT, AATGAAGT, ATTCCGAA, AATTTAAG, CTCCCGAC, TTCAATGA, TCATGAAT, TAATAAAT, AATTAATT, GTCTAAAC, AATCTAAA, AAATTGAT, AGAAATGT, GTCTGAAA, TTTCATAA, TGAATAAA, TGATAATA, TGTTAAAC, TTCTCAAA, TTCTAATA, ATAAAGAG, AACTTAAA, AATTGATA, ATTAAAGT, AACGAAAT, ATTAATAA, TTCAATAT, TCATAGAG, CTTTAAAC, TCTTTAAA, TAAAGAAT, TCTTAAAT, GTCTTCCA, AAATCTTC, GTTAAATA, GTCTTAAC, GTTCTAAA, AATCTTAA, AAATCCTG, AATCCCTT, AGACCCGT, AGAAATTT, AGAAATTG, TCCTCTTA, TTTAATAA, TAAATTTA, TTCTTCAC, AATTTAAT, TGAAATTA, TAAATTGA, TAAATTAA, TTAAATGA, TGAAATAA, TAATTGAA, TGAATAAC, TTCTGAAC, TGAATGAA, TGAAATGA, TTCTTCAA, AATTAAAT, TCCTCTTC, TCCTAATA, TAAATGAG, TGAATTAA, TTCCATTA, TCCTCATT, TATTAAAT, TAATTAAG, TTAATGAA, TGATGAAC, TATTTAAC, TATTCAAT, TTCGAAAC, TAAATAAA, TAATGAAA, TTTCTAAA, TTGATAAC, TTCTTAAC, TCCTCAAA, AATAAATG, TCCTTCAC, TCCTGAAC, TGATTAAC, TTCTAAAG, AGAAATAA, AAATGAAT, ATCCTGAC, ATTCTAAA, GTCTAAAT, AAATTCTC, AAATTTAT, ATTAAATT, ATTCCTTA, AAATCTTG, AATCTTCA, AATTTAAA, GTCTAATA, GTGAAATA, GTTGAAAC, ATTTAATA, AGAAATTC, AATCTCTC, GTAAATTA, AAATGAAA, AATTTCTC, AATTAAAG, AAATTAAA, ATTTAAAG, AAATTTAA, AAATCTTA, AGAAATTA, AATCTAAG, AAATTCTA, ATTCTAAG, AAATTCGT, ATCCTTTA, ATTAATTA, AATCTGAT, AAATCTCA, ATTAATGA, ATTTAAAT, ATCTAATG, ATTCTTAA, AAATCTTT,58 / 235B1195.70202WO00#14468377 v2GTAAATGA, AAATTCGA, AAATTAAG, AGATGAAA, GTTAATAA, AGAAATGA, GTGATAAA, AATTAATC, GTTCTAAC, AAATTCTG, AAATTGAA, AAATCTAA, AATTCTTA, GTTAAACA, TTTATAAC, AACGAATA, ATAAAGAA, AATAATGA, ATTTAAGC, AATAAGAA, AATTAAAC, AGATTTAA, ATCTTCGA, TCCTTAAA, TGATAAGC, TAAATTAT, TAAATTAG, AATAAGAG, AATAAATA, AATAATTC, AATATGAG, ATTAATAT, AATTCGTC, ACACCCGT, AATCTTTA, AATGAAAT, GATTAAGA, AAATAATG, TAAATGAA, TAAATGAC, GAAATTTA, GAAATTTC, ATTAAATG, ATTAATAC, GAAATAAT, AACGATGA, ATAAATAA, AGATCTTG, AGTTTAAC, AAAACTTG, AAAAGAAA, AACACTTG, AACAGAAA, AACATAAC, TCATGAAA, TCATTCAA, TCTATAAC, GCTTAAGA, ACATAATG, TCAATGAA, ATGAAATG, ATGAATAC, AAGATAAC, GAGATAAT, AAGGATGA, ATGAATAA, TAAGGAAA, TGAGTCAA, TTTGTAAC, GATGAAGA, TAAGTGAA, ATTTAATG, ATTTATAC, GAATTAAT, AACTATGA, ATATATAA, TTATGAAA, TAATTAAA, TTAATAAC, TGATTAAA, TAAATAAG, TGAATAGA, TTACTAAA, TTATTAAA, TAGTGAAA, TTTAGAAC, TGGTTCAA, TAGATGAG, TGGAATGA, TTTCGAAA, or TTGTGAAA. In certain embodiments, the linker comprises a sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to, or comprising one, two, three, four, or five mutations relative to, the sequence AAATCTTG. In certain embodiments, the linker comprises a sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to, or comprising one, two, three, four, or five mutations relative to, the sequence TAATGAAA. In certain embodiments, the linker comprises a sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to, or comprising one, two, three, four, or five mutations relative to, the sequence TCTATAAC. In certain embodiments, the linker comprises a sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to, or comprising one, two, three, four, or five mutations relative to, the sequence TGAAATGA. In certain embodiments, the linker comprises a sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to, or comprising one, two, three, four, or five mutations relative to, the sequence TTACTAAA.

[0156] In some embodiments, the pegRNA comprises the structure 5 '-[spacer] -[backbone scaffold] -[edit template] -[primer binding site] -[linker] -[structured motif] -3'.59 / 235B1195.70202WO00#14468377 v2

[0157] In some embodiments, the pegRNA comprises a sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to, or comprising one, two, three, four, or five mutations relative to, the sequence:GTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTTT AAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCAGT CCTTTCGAGTACCCAAATTAACCGCGGTTCTATCTAGTTACGCGTTAAACCAACT AGAA (SEQ ID NO: 304), GTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTTT AAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCGCA GTCCTTTCGAGTACCCTGCCCAACCGCGGTTCTATCTAGTTACGCGTTAAACCAA CTAGAA (SEQ ID NO: 305), GTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTTT AAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTACG CAGTCCTTTCGAGTACCCTGCCATCCCGCGGTTCTATCTAGTTACGCGTTAAACCA ACTAGAA (SEQ ID NO: 306), GTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTTT AAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGTA CGCAGTCCTTTCGAGTACCCTGATCCCTCGCGGTTCTATCTAGTTACGCGTTAAAC CAACTAGAA (SEQ ID NO: 307), GTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTTT AAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGTGG TACGCAGTCCTTTCGAGTACCCTTCTCTCACGCGGTTCTATCTAGTTACGCGTTAA ACCAACTAGAA (SEQ ID NO: 308), GTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTTT AAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGTGT GGTACGCAGTCCTTTCGAGTACCCTGATCCAACGCGGTTCTATCTAGTTACGCGT TAAACCAACTAGAA (SEQ ID NO: 309), GTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTTT AAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCTCTC CTTTCGAGTACCCTAACCAATCGCGGTTCTATCTAGTTACGCGTTAAACCAACTA GAA (SEQ ID NO: 310), GTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTTT AAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCGCT60 / 235B1195.70202WO00#14468377 v2CTCCTTTCGAGTACCCTGATCCACCGCGGTTCTATCTAGTTACGCGTTAAACCAAC TAGAA (SEQ ID NO: 311), GTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTTT AAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTACG CGCTCTCCTTTCGAGTACCCTATTTAAACGCGGTTCTATCTAGTTACGCGTTAAAC CAACTAGAA (SEQ ID NO: 312), GTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTTT AAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGTA CGCTCTCCTTTCGAGTACCCTTTCCTCACGCGGTTCTATCTAGTTACGCGTTAAAC CAACTAGAA (SEQ ID NO: 313), GTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTTT AAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGTGG TACGCTCTCCTTTCGAGTACCCTTCCTCTACGCGGTTCTATCTAGTTACGCGTTAA ACCAACTAGAA (SEQ ID NO: 314), GTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTTT AAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGTGT GGTACGCTCTCCTTTCGAGTACCCTTCTCCTCCGCGGTTCTATCTAGTTACGCGTT AAACCAACTAGAA (SEQ ID NO: 315), GTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTTT AAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCAGT CCTTTCGAGTACCCACAAAGGATACGCGGTTCTATCTAGTTACGCGTTAAACCAA CTAGAA (SEQ ID NO: 316), GTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTTT AAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCGCA GTCCTTTCGAGTACCCACCAATTAATCGCGGTTCTATCTAGTTACGCGTTAAACC AACTAGAA (SEQ ID NO: 317), GTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTTT AAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTACG CAGTCCTTTCGAGTACCCACCATTAAGCCGCGGTTCTATCTAGTTACGCGTTAAA CCAACTAGAA (SEQ ID NO: 318), GTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTTT AAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGTA CGCAGTCCTTTCGAGTACCCACTCCCTTCCCGCGGTTCTATCTAGTTACGCGTTAA61 / 235B1195.70202WO00#14468377 v2ACCAACTAGAA (SEQ ID NO: 319), GTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTTT AAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGTGG TACGCAGTCCTTTCGAGTACCCACTCCTGAATCGCGGTTCTATCTAGTTACGCGTT AAACCAACTAGAA (SEQ ID NO: 320), GTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTTT AAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGTGT GGTACGCAGTCCTTTCGAGTACCCACTCCTTAATCGCGGTTCTATCTAGTTACGCG TTAAACCAACTAGAA (SEQ ID NO: 321), GTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTTT AAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCTCTC CTTTCGAGTACCCACCCAATATCCGCGGTTCTATCTAGTTACGCGTTAAACCAAC TAGAA (SEQ ID NO: 322), GTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTTT AAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCGCT CTCCTTTCGAGTACCCACCTTCCTCTCGCGGTTCTATCTAGTTACGCGTTAAACCA ACTAGAA (SEQ ID NO: 323), GTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTTT AAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTACG CGCTCTCCTTTCGAGTACCCACCCAATTCCCGCGGTTCTATCTAGTTACGCGTTAA ACCAACTAGAA (SEQ ID NO: 324), GTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTTT AAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGTA CGCTCTCCTTTCGAGTACCCACTCCCTTCTCGCGGTTCTATCTAGTTACGCGTTAA ACCAACTAGAA (SEQ ID NO: 325), GTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTTT AAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGTGG TACGCTCTCCTTTCGAGTACCCACTCAAATCTCGCGGTTCTATCTAGTTACGCGTT AAACCAACTAGAA (SEQ ID NO: 326), GTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTTT AAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGTGT GGTACGCTCTCCTTTCGAGTACCCACTCCTAAATCGCGGTTCTATCTAGTTACGCG TTAAACCAACTAGAA (SEQ ID NO: 327),62 / 235B1195.70202WO00#14468377 v2GTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTTT AAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCAGT CCTTTCGAGTACCCACAGAAAGATAACGCGGTTCTATCTAGTTACGCGTTAAACC AACTAGAA (SEQ ID NO: 328), GTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTTT AAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCGCA GTCCTTTCGAGTACCCACAGAAAGAATGCGCGGTTCTATCTAGTTACGCGTTAAA CCAACTAGAA (SEQ ID NO: 329), GTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTTT AAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTACG CAGTCCTTTCGAGTACCCACAGAAAGAATACGCGGTTCTATCTAGTTACGCGTTA AACCAACTAGAA (SEQ ID NO: 330), GTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTTT AAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGTA CGCAGTCCTTTCGAGTACCCACAGCTTCCCATCGCGGTTCTATCTAGTTACGCGTT AAACCAACTAGAA (SEQ ID NO: 331), GTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTTT AAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGTGG TACGCAGTCCTTTCGAGTACCCACAGCCTGTTCACGCGGTTCTATCTAGTTACGC GTTAAACCAACTAGAA (SEQ ID NO: 332), GTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTTT AAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGTGT GGTACGCAGTCCTTTCGAGTACCCACAGGAGAATAGCGCGGTTCTATCTAGTTAC GCGTTAAACCAACTAGAA (SEQ ID NO: 333), GTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTTT AAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCTCTC CTTTCGAGTACCCACAGGAGAACCTCGCGGTTCTATCTAGTTACGCGTTAAACCA ACTAGAA (SEQ ID NO: 334), GTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTTT AAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCGCT CTCCTTTCGAGTACCCACAGCCTCCATTCGCGGTTCTATCTAGTTACGCGTTAAAC CAACTAGAA (SEQ ID NO: 335), GTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTTT63 / 235B1195.70202WO00#14468377 v2AAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTACG CGCTCTCCTTTCGAGTACCCACAGCAGAGAATCGCGGTTCTATCTAGTTACGCGT TAAACCAACTAGAA (SEQ ID NO: 336), GTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTTT AAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGTA CGCTCTCCTTTCGAGTACCCACAGCCTCCGAACGCGGTTCTATCTAGTTACGCGTT AAACCAACTAGAA (SEQ ID NO: 337), GTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTTT AAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGTGG TACGCTCTCCTTTCGAGTACCCACAGCCTAAAGGCGCGGTTCTATCTAGTTACGC GTTAAACCAACTAGAA (SEQ ID NO: 338), GTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTTT AAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGTGT GGTACGCTCTCCTTTCGAGTACCCACAGCTTAGTAACGCGGTTCTATCTAGTTAC GCGTTAAACCAACTAGAA (SEQ ID NO: 339), GTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTTT AAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCAGT CCTTTCGAGTACCCACAGTAAATATAACCGCGGTTCTATCTAGTTACGCGTTAAA CCAACTAGAA (SEQ ID NO: 340), GTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTTT AAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCGCA GTCCTTTCGAGTACCCACAGTAAATAAGTCCGCGGTTCTATCTAGTTACGCGTTA AACCAACTAGAA (SEQ ID NO: 341), GTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTTT AAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTACG CAGTCCTTTCGAGTACCCACAGTAATATAAACCGCGGTTCTATCTAGTTACGCGT TAAACCAACTAGAA (SEQ ID NO: 342), GTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTTT AAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGTA CGCAGTCCTTTCGAGTACCCACAGTAATCATAATCGCGGTTCTATCTAGTTACGC GTTAAACCAACTAGAA (SEQ ID NO: 343), GTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTTT AAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGTGG64 / 235B1195.70202WO00#14468377 v2TACGCAGTCCTTTCGAGTACCCACAGTAGAAAGAAGCGCGGTTCTATCTAGTTAC GCGTTAAACCAACTAGAA (SEQ ID NO: 344), GTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTTT AAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGTGT GGTACGCAGTCCTTTCGAGTACCCACAGTAATCAGATACGCGGTTCTATCTAGTT ACGCGTTAAACCAACTAGAA (SEQ ID NO: 345), GTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTTT AAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCTCTC CTTTCGAGTACCCACAGTAATAATAATCGCGGTTCTATCTAGTTACGCGTTAAAC CAACTAGAA (SEQ ID NO: 346), GTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTTT AAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCGCT CTCCTTTCGAGTACCCACAGTAGATTAATACGCGGTTCTATCTAGTTACGCGTTA AACCAACTAGAA (SEQ ID NO: 347), GTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTTT AAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTACG CGCTCTCCTTTCGAGTACCCACAGTAGATCCATACGCGGTTCTATCTAGTTACGC GTTAAACCAACTAGAA (SEQ ID NO: 348), GTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTTT AAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGTA CGCTCTCCTTTCGAGTACCCACAGTAATTCCGACCGCGGTTCTATCTAGTTACGCG TTAAACCAACTAGAA (SEQ ID NO: 349), GTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTTT AAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGTGG TACGCTCTCCTTTCGAGTACCCACAGTAGAGAAGAACGCGGTTCTATCTAGTTAC GCGTTAAACCAACTAGAA (SEQ ID NO: 350), GTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTTT AAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGTGT GGTACGCTCTCCTTTCGAGTACCCACAGTAGGATAATCCGCGGTTCTATCTAGTT ACGCGTTAAACCAACTAGAA (SEQ ID NO: 351), AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCA GTCCTTTCGAGTACCCAATTAATACGCGGTTCTATCTAGTTACGCGTTAAACCAA65 / 235B1195.70202WO00#14468377 v2CTAGAA (SEQ ID NO: 352), AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCGC AGTCCTTTCGAGTACCCTAATAATGCGCGGTTCTATCTAGTTACGCGTTAAACCA ACTAGAA (SEQ ID NO: 353), AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTAC GCAGTCCTTTCGAGTACCCTAATAAACCGCGGTTCTATCTAGTTACGCGTTAAAC CAACTAGAA (SEQ ID NO: 354), AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT ACGCAGTCCTTTCGAGTACCCTTTCCGACCGCGGTTCTATCTAGTTACGCGTTAAA CCAACTAGAA (SEQ ID NO: 355), AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGTG GTACGCAGTCCTTTCGAGTACCCTTCTCCACCGCGGTTCTATCTAGTTACGCGTTA AACCAACTAGAA (SEQ ID NO: 356), AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGTG TGGTACGCAGTCCTTTCGAGTACCCTGAATCCACGCGGTTCTATCTAGTTACGCG TTAAACCAACTAGAA (SEQ ID NO: 357), AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCTC TCCTTTCGAGTACCCTAATAATACGCGGTTCTATCTAGTTACGCGTTAAACCAACT AGAA (SEQ ID NO: 358), AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCGC TCTCCTTTCGAGTACCCTTCCATCACGCGGTTCTATCTAGTTACGCGTTAAACCAA CTAGAA (SEQ ID NO: 359), AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTAC GCGCTCTCCTTTCGAGTACCCTGATCATACGCGGTTCTATCTAGTTACGCGTTAAA CCAACTAGAA (SEQ ID NO: 360),66 / 235B1195.70202WO00#14468377 v2AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT ACGCTCTCCTTTCGAGTACCCTTCCTCCTCGCGGTTCTATCTAGTTACGCGTTAAA CCAACTAGAA (SEQ ID NO: 361), AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGTG GTACGCTCTCCTTTCGAGTACCCTGATCCATCGCGGTTCTATCTAGTTACGCGTTA AACCAACTAGAA (SEQ ID NO: 362), AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGTG TGGTACGCTCTCCTTTCGAGTACCCTTCTCCGACGCGGTTCTATCTAGTTACGCGT TAAACCAACTAGAA (SEQ ID NO: 363), AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCA GTCCTTTCGAGTACCCACAAAGGATTCGCGGTTCTATCTAGTTACGCGTTAAACC AACTAGAA (SEQ ID NO: 364), AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCGC AGTCCTTTCGAGTACCCACCAATAATACGCGGTTCTATCTAGTTACGCGTTAAAC CAACTAGAA (SEQ ID NO: 365), AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTAC GCAGTCCTTTCGAGTACCCACCACCTATCCGCGGTTCTATCTAGTTACGCGTTAA ACCAACTAGAA (SEQ ID NO: 366), AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT ACGCAGTCCTTTCGAGTACCCACCCTTTCGACGCGGTTCTATCTAGTTACGCGTTA AACCAACTAGAA (SEQ ID NO: 367), AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGTG GTACGCAGTCCTTTCGAGTACCCACCCTTTAACCGCGGTTCTATCTAGTTACGCGT TAAACCAACTAGAA (SEQ ID NO: 368), AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT67 / 235B1195.70202WO00#14468377 v2TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGTG TGGTACGCAGTCCTTTCGAGTACCCACTCCAAGAGCGCGGTTCTATCTAGTTACG CGTTAAACCAACTAGAA (SEQ ID NO: 369), AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCTC TCCTTTCGAGTACCCACCAATCAACCGCGGTTCTATCTAGTTACGCGTTAAACCA ACTAGAA (SEQ ID NO: 370), AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCGC TCTCCTTTCGAGTACCCACTAATAGAACGCGGTTCTATCTAGTTACGCGTTAAAC CAACTAGAA (SEQ ID NO: 371), AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTAC GCGCTCTCCTTTCGAGTACCCACCCAATCCACGCGGTTCTATCTAGTTACGCGTTA AACCAACTAGAA (SEQ ID NO: 372), AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT ACGCTCTCCTTTCGAGTACCCACTTCCAAATCGCGGTTCTATCTAGTTACGCGTTA AACCAACTAGAA (SEQ ID NO: 373), AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGTG GTACGCTCTCCTTTCGAGTACCCACTCCAATCCCGCGGTTCTATCTAGTTACGCGT TAAACCAACTAGAA (SEQ ID NO: 374), AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGTG TGGTACGCTCTCCTTTCGAGTACCCACTTCAAATTCGCGGTTCTATCTAGTTACGC GTTAAACCAACTAGAA (SEQ ID NO: 375), AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCA GTCCTTTCGAGTACCCACAGCAAGGAGACGCGGTTCTATCTAGTTACGCGTTAAA CCAACTAGAA (SEQ ID NO: 376), AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCGC68 / 235B1195.70202WO00#14468377 v2AGTCCTTTCGAGTACCCACAGAAGAGAAACGCGGTTCTATCTAGTTACGCGTTAA ACCAACTAGAA (SEQ ID NO: 377), AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTAC GCAGTCCTTTCGAGTACCCACAGAAAGATTTCGCGGTTCTATCTAGTTACGCGTT AAACCAACTAGAA (SEQ ID NO: 378), AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT ACGCAGTCCTTTCGAGTACCCACAGCGAGAAATCGCGGTTCTATCTAGTTACGCG TTAAACCAACTAGAA (SEQ ID NO: 379), AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGTG GTACGCAGTCCTTTCGAGTACCCACAGCCGTCCGACGCGGTTCTATCTAGTTACG CGTTAAACCAACTAGAA (SEQ ID NO: 380), AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGTG TGGTACGCAGTCCTTTCGAGTACCCACAGCGAAGAAGCGCGGTTCTATCTAGTTA CGCGTTAAACCAACTAGAA (SEQ ID NO: 381), AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCTC TCCTTTCGAGTACCCACAGGAGGACCACGCGGTTCTATCTAGTTACGCGTTAAAC CAACTAGAA (SEQ ID NO: 382), AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCGC TCTCCTTTCGAGTACCCACAGAAGAAATACGCGGTTCTATCTAGTTACGCGTTAA ACCAACTAGAA (SEQ ID NO: 383), AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTAC GCGCTCTCCTTTCGAGTACCCACAGAGAAGATCCGCGGTTCTATCTAGTTACGCG TTAAACCAACTAGAA (SEQ ID NO: 384), AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT ACGCTCTCCTTTCGAGTACCCACAGAAGAAGAACGCGGTTCTATCTAGTTACGCG69 / 235B1195.70202WO00#14468377 v2TTAAACCAACTAGAA (SEQ ID NO: 385), AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGTG GTACGCTCTCCTTTCGAGTACCCACAGCCGGAGACCGCGGTTCTATCTAGTTACG CGTTAAACCAACTAGAA (SEQ ID NO: 386), AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGTG TGGTACGCTCTCCTTTCGAGTACCCACAGCCGTTCATCGCGGTTCTATCTAGTTAC GCGTTAAACCAACTAGAA (SEQ ID NO: 387), AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCA GTCCTTTCGAGTACCCACAGTAAATAATTTCGCGGTTCTATCTAGTTACGCGTTAA ACCAACTAGAA (SEQ ID NO: 388), AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCGC AGTCCTTTCGAGTACCCACAGTAAGATAAATCGCGGTTCTATCTAGTTACGCGTT AAACCAACTAGAA (SEQ ID NO: 389), AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTAC GCAGTCCTTTCGAGTACCCACAGTAAAGATCCACGCGGTTCTATCTAGTTACGCG TTAAACCAACTAGAA (SEQ ID NO: 390), AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT ACGCAGTCCTTTCGAGTACCCACAGTAAGAAGAATCGCGGTTCTATCTAGTTACG CGTTAAACCAACTAGAA (SEQ ID NO: 391), AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGTG GTACGCAGTCCTTTCGAGTACCCACAGTAAGAAGAAGCGCGGTTCTATCTAGTTA CGCGTTAAACCAACTAGAA (SEQ ID NO: 392), AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGTG TGGTACGCAGTCCTTTCGAGTACCCACAGTAAGGAATGACGCGGTTCTATCTAGT TACGCGTTAAACCAACTAGAA (SEQ ID NO: 393),70 / 235B1195.70202WO00#14468377 v2AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCTC TCCTTTCGAGTACCCACAGTAAATAAATTCGCGGTTCTATCTAGTTACGCGTTAA ACCAACTAGAA (SEQ ID NO: 394), AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCGC TCTCCTTTCGAGTACCCACAGTAAGATCCCTCGCGGTTCTATCTAGTTACGCGTTA AACCAACTAGAA (SEQ ID NO: 395), AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTAC GCGCTCTCCTTTCGAGTACCCACAGTAAATTCAATCGCGGTTCTATCTAGTTACGC GTTAAACCAACTAGAA (SEQ ID NO: 396), AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT ACGCTCTCCTTTCGAGTACCCACAGTAAATATTTCCGCGGTTCTATCTAGTTACGC GTTAAACCAACTAGAA (SEQ ID NO: 397), AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGTG GTACGCTCTCCTTTCGAGTACCCACAGTAAGAAGTATCGCGGTTCTATCTAGTTA CGCGTTAAACCAACTAGAA (SEQ ID NO: 398), AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGTG TGGTACGCTCTCCTTTCGAGTACCCACAGTAGGATAATCCGCGGTTCTATCTAGTT ACGCGTTAAACCAACTAGAA (SEQ ID NO: 399), GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGCA GTCCGTTCGAGTACCGGGCTACCCGCGGTTCTATCTAGTTACGCGTTAAACCAAC TAGAA (SEQ ID NO: 400), GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGCA GTCCGTTCGAGTACCCTAATAATTCGCGGTTCTATCTAGTTACGCGTTAAACCAA CTAGAA (SEQ ID NO: 401), GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT71 / 235B1195.70202WO00#14468377 v2TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGCA GTCCGTTCGAGTACCCAGGATTAAACGCGGTTCTATCTAGTTACGCGTTAAACCA ACTAGAA (SEQ ID NO: 402), GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGCA GTCCGTTCGAGTACCCACCACTGTAGCGCGGTTCTATCTAGTTACGCGTTAAACC AACTAGAA (SEQ ID NO: 403), GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGCA GTCCGTTCGAGTACCCACAACCATTAGCGCGGTTCTATCTAGTTACGCGTTAAAC CAACTAGAA (SEQ ID NO: 404), GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGCA GTCCGTTCGAGTACCCACAGCCATTTAGCGCGGTTCTATCTAGTTACGCGTTAAA CCAACTAGAA (SEQ ID NO: 405), GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGCTC TCCGTTCGAGTACCGTTAACCACGCGGTTCTATCTAGTTACGCGTTAAACCAACT AGAA (SEQ ID NO: 406), GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGCTC TCCGTTCGAGTACCCTTCTAAACCGCGGTTCTATCTAGTTACGCGTTAAACCAACT AGAA (SEQ ID NO: 407), GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGCTC TCCGTTCGAGTACCCAATTTCCATCGCGGTTCTATCTAGTTACGCGTTAAACCAAC TAGAA (SEQ ID NO: 408), GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGCTC TCCGTTCGAGTACCCACCCTTAAAGCGCGGTTCTATCTAGTTACGCGTTAAACCA ACTAGAA (SEQ ID NO: 409), GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGCTC72 / 235B1195.70202WO00#14468377 v2TCCGTTCGAGTACCCACACCCAAGATCGCGGTTCTATCTAGTTACGCGTTAAACC AACTAGAA (SEQ ID NO: 410), GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGCTC TCCGTTCGAGTACCCACAGGAGTTCAACGCGGTTCTATCTAGTTACGCGTTAAAC CAACTAGAA (SEQ ID NO: 411), GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCGC AGTCCGTTCGAGTACCGTGTCCCACGCGGTTCTATCTAGTTACGCGTTAAACCAA CTAGAA (SEQ ID NO: 412), GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCGC AGTCCGTTCGAGTACCCTAATAATTCGCGGTTCTATCTAGTTACGCGTTAAACCA ACTAGAA (SEQ ID NO: 413), GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCGC AGTCCGTTCGAGTACCCAAATAATTTCGCGGTTCTATCTAGTTACGCGTTAAACC AACTAGAA (SEQ ID NO: 414), GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCGC AGTCCGTTCGAGTACCCACTGATAAACCGCGGTTCTATCTAGTTACGCGTTAAAC CAACTAGAA (SEQ ID NO: 415), GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCGC AGTCCGTTCGAGTACCCACAATAATTTACGCGGTTCTATCTAGTTACGCGTTAAA CCAACTAGAA (SEQ ID NO: 416), GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCGC AGTCCGTTCGAGTACCCACAGCCTGTCTACGCGGTTCTATCTAGTTACGCGTTAA ACCAACTAGAA (SEQ ID NO: 417), GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCGCT CTCCGTTCGAGTACCAGATCCTTCGCGGTTCTATCTAGTTACGCGTTAAACCAACT73 / 235B1195.70202WO00#14468377 v2AGAA (SEQ ID NO: 418), GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCGCT CTCCGTTCGAGTACCCTAATCCCTCGCGGTTCTATCTAGTTACGCGTTAAACCAAC TAGAA (SEQ ID NO: 419), GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCGCT CTCCGTTCGAGTACCCAAATAATCCCGCGGTTCTATCTAGTTACGCGTTAAACCA ACTAGAA (SEQ ID NO: 420), GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCGCT CTCCGTTCGAGTACCCACCTTCCTTACGCGGTTCTATCTAGTTACGCGTTAAACCA ACTAGAA (SEQ ID NO: 421), GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCGCT CTCCGTTCGAGTACCCACAAATTAATGCGCGGTTCTATCTAGTTACGCGTTAAAC CAACTAGAA (SEQ ID NO: 422), GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCGCT CTCCGTTCGAGTACCCACAGCCTTCAAACGCGGTTCTATCTAGTTACGCGTTAAA CCAACTAGAA (SEQ ID NO: 423), GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCACG CAGTCCGTTCGAGTACCAAATAAAGCGCGGTTCTATCTAGTTACGCGTTAAACCA ACTAGAA (SEQ ID NO: 424), GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCACG CAGTCCGTTCGAGTACCCTGTTCAACCGCGGTTCTATCTAGTTACGCGTTAAACC AACTAGAA (SEQ ID NO: 425), GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCACG CAGTCCGTTCGAGTACCCAAATAAAGACGCGGTTCTATCTAGTTACGCGTTAAAC CAACTAGAA (SEQ ID NO: 426),74 / 235B1195.70202WO00#14468377 v2GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCACG CAGTCCGTTCGAGTACCCACCGCCTAATCGCGGTTCTATCTAGTTACGCGTTAAA CCAACTAGAA (SEQ ID NO: 427), GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCACG CAGTCCGTTCGAGTACCCACAAACTGTTACGCGGTTCTATCTAGTTACGCGTTAA ACCAACTAGAA (SEQ ID NO: 428), GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCACG CAGTCCGTTCGAGTACCCACAGCCATCCACCGCGGTTCTATCTAGTTACGCGTTA AACCAACTAGAA (SEQ ID NO: 429), GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCACG CTCTCCGTTCGAGTACCAGATCCCTCGCGGTTCTATCTAGTTACGCGTTAAACCA ACTAGAA (SEQ ID NO: 430), GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCACG CTCTCCGTTCGAGTACCCTGATCATACGCGGTTCTATCTAGTTACGCGTTAAACCA ACTAGAA (SEQ ID NO: 431), GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCACG CTCTCCGTTCGAGTACCCAATCCATTTCGCGGTTCTATCTAGTTACGCGTTAAACC AACTAGAA (SEQ ID NO: 432), GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCACG CTCTCCGTTCGAGTACCCACCCAAATTTCGCGGTTCTATCTAGTTACGCGTTAAAC CAACTAGAA (SEQ ID NO: 433), GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCACG CTCTCCGTTCGAGTACCCACAATTTAATCCGCGGTTCTATCTAGTTACGCGTTAAA CCAACTAGAA (SEQ ID NO: 434), GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT75 / 235B1195.70202WO00#14468377 v2TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCACG CTCTCCGTTCGAGTACCCACAGCCTTCCACCGCGGTTCTATCTAGTTACGCGTTAA ACCAACTAGAA (SEQ ID NO: 435), GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTAC GCAGTCCGTTCGAGTACCGGATATCCCGCGGTTCTATCTAGTTACGCGTTAAACC AACTAGAA (SEQ ID NO: 436), GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTAC GCAGTCCGTTCGAGTACCCTGTCCAAGCGCGGTTCTATCTAGTTACGCGTTAAAC CAACTAGAA (SEQ ID NO: 437), GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTAC GCAGTCCGTTCGAGTACCCAGCGCCCTCCGCGGTTCTATCTAGTTACGCGTTAAA CCAACTAGAA (SEQ ID NO: 438), GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTAC GCAGTCCGTTCGAGTACCCACCACCTGTACGCGGTTCTATCTAGTTACGCGTTAA ACCAACTAGAA (SEQ ID NO: 439), GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTAC GCAGTCCGTTCGAGTACCCACAACCATTAACGCGGTTCTATCTAGTTACGCGTTA AACCAACTAGAA (SEQ ID NO: 440), GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTAC GCAGTCCGTTCGAGTACCCACAGCCATATCTCGCGGTTCTATCTAGTTACGCGTT AAACCAACTAGAA (SEQ ID NO: 441), GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTAC GCTCTCCGTTCGAGTACCAATCTAATCGCGGTTCTATCTAGTTACGCGTTAAACC AACTAGAA (SEQ ID NO: 442), GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTAC76 / 235B1195.70202WO00#14468377 v2GCTCTCCGTTCGAGTACCCTAAATCTGCGCGGTTCTATCTAGTTACGCGTTAAACC AACTAGAA (SEQ ID NO: 443), GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTAC GCTCTCCGTTCGAGTACCCAAACCTTCTCGCGGTTCTATCTAGTTACGCGTTAAAC CAACTAGAA (SEQ ID NO: 444), GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTAC GCTCTCCGTTCGAGTACCCACCCTTTAATCGCGGTTCTATCTAGTTACGCGTTAAA CCAACTAGAA (SEQ ID NO: 445), GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTAC GCTCTCCGTTCGAGTACCCACAATTAATTCCGCGGTTCTATCTAGTTACGCGTTAA ACCAACTAGAA (SEQ ID NO: 446), GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTAC GCTCTCCGTTCGAGTACCCACAGCCAAATCGCGCGGTTCTATCTAGTTACGCGTT AAACCAACTAGAA (SEQ ID NO: 447), GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGTA CGCAGTCCGTTCGAGTACCATTTCCTACGCGGTTCTATCTAGTTACGCGTTAAACC AACTAGAA (SEQ ID NO: 448), GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGTA CGCAGTCCGTTCGAGTACCCTAATCCTTCGCGGTTCTATCTAGTTACGCGTTAAAC CAACTAGAA (SEQ ID NO: 449), GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGTA CGCAGTCCGTTCGAGTACCCAAATCAATCCGCGGTTCTATCTAGTTACGCGTTAA ACCAACTAGAA (SEQ ID NO: 450), GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGTA CGCAGTCCGTTCGAGTACCCACCTTCCCGCCGCGGTTCTATCTAGTTACGCGTTA77 / 235B1195.70202WO00#14468377 v2AACCAACTAGAA (SEQ ID NO: 451), GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGTA CGCAGTCCGTTCGAGTACCCACACCCTTTCTCGCGGTTCTATCTAGTTACGCGTTA AACCAACTAGAA (SEQ ID NO: 452), GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGTA CGCAGTCCGTTCGAGTACCCACAGCCTTCTAACGCGGTTCTATCTAGTTACGCGT TAAACCAACTAGAA (SEQ ID NO: 453), GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGTA CGCTCTCCGTTCGAGTACCGTCTATCCCGCGGTTCTATCTAGTTACGCGTTAAACC AACTAGAA (SEQ ID NO: 454), GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGTA CGCTCTCCGTTCGAGTACCCTGATAAAGCGCGGTTCTATCTAGTTACGCGTTAAA CCAACTAGAA (SEQ ID NO: 455), GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGTA CGCTCTCCGTTCGAGTACCCAAATGAATACGCGGTTCTATCTAGTTACGCGTTAA ACCAACTAGAA (SEQ ID NO: 456), GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGTA CGCTCTCCGTTCGAGTACCCACCTTTAAAGCGCGGTTCTATCTAGTTACGCGTTAA ACCAACTAGAA (SEQ ID NO: 457), GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGTA CGCTCTCCGTTCGAGTACCCACACCCTTAGCCGCGGTTCTATCTAGTTACGCGTTA AACCAACTAGAA (SEQ ID NO: 458), GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGTA CGCTCTCCGTTCGAGTACCCACAGCCAAGAATCGCGGTTCTATCTAGTTACGCGT TAAACCAACTAGAA (SEQ ID NO: 459),78 / 235B1195.70202WO00#14468377 v2GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT ACGCAGTCCGTTCGAGTACCAAATTTCACGCGGTTCTATCTAGTTACGCGTTAAA CCAACTAGAA (SEQ ID NO: 460), GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT ACGCAGTCCGTTCGAGTACCCTGAATCCTCGCGGTTCTATCTAGTTACGCGTTAA ACCAACTAGAA (SEQ ID NO: 461), GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT ACGCAGTCCGTTCGAGTACCCAAATCCTATCGCGGTTCTATCTAGTTACGCGTTA AACCAACTAGAA (SEQ ID NO: 462), GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT ACGCAGTCCGTTCGAGTACCCACCCATTCCTCGCGGTTCTATCTAGTTACGCGTTA AACCAACTAGAA (SEQ ID NO: 463), GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT ACGCAGTCCGTTCGAGTACCCACATCCTTAATCGCGGTTCTATCTAGTTACGCGTT AAACCAACTAGAA (SEQ ID NO: 464), GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT ACGCAGTCCGTTCGAGTACCCACAGCCTTAATCCGCGGTTCTATCTAGTTACGCG TTAAACCAACTAGAA (SEQ ID NO: 465), GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT ACGCTCTCCGTTCGAGTACCAATCTCTTCGCGGTTCTATCTAGTTACGCGTTAAAC CAACTAGAA (SEQ ID NO: 466), GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT ACGCTCTCCGTTCGAGTACCCTGATCCTCCGCGGTTCTATCTAGTTACGCGTTAAA CCAACTAGAA (SEQ ID NO: 467), GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT79 / 235B1195.70202WO00#14468377 v2TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT ACGCTCTCCGTTCGAGTACCCAATTAAATACGCGGTTCTATCTAGTTACGCGTTA AACCAACTAGAA (SEQ ID NO: 468), GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT ACGCTCTCCGTTCGAGTACCCACTTCAATTCCGCGGTTCTATCTAGTTACGCGTTA AACCAACTAGAA (SEQ ID NO: 469), GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT ACGCTCTCCGTTCGAGTACCCACAATTAAGAACGCGGTTCTATCTAGTTACGCGT TAAACCAACTAGAA (SEQ ID NO: 470), GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT ACGCTCTCCGTTCGAGTACCCACAGCCTAGAAACGCGGTTCTATCTAGTTACGCG TTAAACCAACTAGAA (SEQ ID NO: 471), GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGTG GTACGCAGTCCGTTCGAGTACCAAATCCTACGCGGTTCTATCTAGTTACGCGTTA AACCAACTAGAA (SEQ ID NO: 472), GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGTG GTACGCAGTCCGTTCGAGTACCCTTCCTAAACGCGGTTCTATCTAGTTACGCGTT AAACCAACTAGAA (SEQ ID NO: 473), GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGTG GTACGCAGTCCGTTCGAGTACCCAATCTCTCTCGCGGTTCTATCTAGTTACGCGTT AAACCAACTAGAA (SEQ ID NO: 474), GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGTG GTACGCAGTCCGTTCGAGTACCCACTTCCTTAACGCGGTTCTATCTAGTTACGCGT TAAACCAACTAGAA (SEQ ID NO: 475), GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGTG80 / 235B1195.70202WO00#14468377 v2GTACGCAGTCCGTTCGAGTACCCACAATTTCCGCCGCGGTTCTATCTAGTTACGC GTTAAACCAACTAGAA (SEQ ID NO: 476), GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGTG GTACGCAGTCCGTTCGAGTACCCACAGGAGAATAGCGCGGTTCTATCTAGTTACG CGTTAAACCAACTAGAA (SEQ ID NO: 477), GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGTG GTACGCTCTCCGTTCGAGTACCGTTTAAACCGCGGTTCTATCTAGTTACGCGTTAA ACCAACTAGAA (SEQ ID NO: 478), GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGTG GTACGCTCTCCGTTCGAGTACCCTTCCTAAACGCGGTTCTATCTAGTTACGCGTTA AACCAACTAGAA (SEQ ID NO: 479), GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGTG GTACGCTCTCCGTTCGAGTACCCAAATTTAACCGCGGTTCTATCTAGTTACGCGTT AAACCAACTAGAA (SEQ ID NO: 480), GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGTG GTACGCTCTCCGTTCGAGTACCCACTCATTTCACGCGGTTCTATCTAGTTACGCGT TAAACCAACTAGAA (SEQ ID NO: 481), GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGTG GTACGCTCTCCGTTCGAGTACCCACACAAATTAGCGCGGTTCTATCTAGTTACGC GTTAAACCAACTAGAA (SEQ ID NO: 482), GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGTG GTACGCTCTCCGTTCGAGTACCCACAGGAATTTAACGCGGTTCTATCTAGTTACG CGTTAAACCAACTAGAA (SEQ ID NO: 483), GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGTGT GGTACGCAGTCCGTTCGAGTACCGTTAAATCCGCGGTTCTATCTAGTTACGCGTT81 / 235B1195.70202WO00#14468377 v2AAACCAACTAGAA (SEQ ID NO: 484), GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGTGT GGTACGCAGTCCGTTCGAGTACCCTTCCTAACCGCGGTTCTATCTAGTTACGCGTT AAACCAACTAGAA (SEQ ID NO: 485), GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGTGT GGTACGCAGTCCGTTCGAGTACCCAATCCTTAACGCGGTTCTATCTAGTTACGCG TTAAACCAACTAGAA (SEQ ID NO: 486), GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGTGT GGTACGCAGTCCGTTCGAGTACCCACTCCCTGAGCGCGGTTCTATCTAGTTACGC GTTAAACCAACTAGAA (SEQ ID NO: 487), GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGTGT GGTACGCAGTCCGTTCGAGTACCCACAAATAGAGGCGCGGTTCTATCTAGTTACG CGTTAAACCAACTAGAA (SEQ ID NO: 488), GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGTGT GGTACGCAGTCCGTTCGAGTACCCACAGCCTGATATCGCGGTTCTATCTAGTTAC GCGTTAAACCAACTAGAA (SEQ ID NO: 489), GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGTGT GGTACGCTCTCCGTTCGAGTACCGTTAAACCCGCGGTTCTATCTAGTTACGCGTT AAACCAACTAGAA (SEQ ID NO: 490), GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGTGT GGTACGCTCTCCGTTCGAGTACCCTTCCCTTCCGCGGTTCTATCTAGTTACGCGTT AAACCAACTAGAA (SEQ ID NO: 491), GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGTGT GGTACGCTCTCCGTTCGAGTACCCAAATCTTCGCGCGGTTCTATCTAGTTACGCGT TAAACCAACTAGAA (SEQ ID NO: 492),82 / 235B1195.70202WO00#14468377 v2GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGTGT GGTACGCTCTCCGTTCGAGTACCCACTCCCTGATCGCGGTTCTATCTAGTTACGCG TTAAACCAACTAGAA (SEQ ID NO: 493), GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGTGT GGTACGCTCTCCGTTCGAGTACCCACAATTTCCCTCGCGGTTCTATCTAGTTACGC GTTAAACCAACTAGAA (SEQ ID NO: 494), GTACTGTGGGTACTCGAAGTGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGTT TAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGTGT GGTACGCTCTCCGTTCGAGTACCCACAGCCTTAGACCGCGGTTCTATCTAGTTAC GCGTTAAACCAACTAGAA (SEQ ID NO: 495), AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTGT GGTACGCAGTCCTTTCGAGTACCGTTAAATCCGCGGTTCTATCTAGTTACGCGTT AAACCAACTAGAA (SEQ ID NO: 496), AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGTG TGGTACGCAGTCCTTTCGAGTACCAAATCCTACGCGGTTCTATCTAGTTACGCGTT AAACCAACTAGAA (SEQ ID NO: 497), AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT GTGGTACGCAGTCCTTTCGAGTACCGTTAACCGCGCGGTTCTATCTAGTTACGCG TTAAACCAACTAGAA (SEQ ID NO: 498), AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGCAGTCCTTTCGAGTACCGTCTCCTCCGCGGTTCTATCTAGTTACGC GTTAAACCAACTAGAA (SEQ ID NO: 499), AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGCAGTCCTTTCGAGTACCGTCTCCCTCGCGGTTCTATCTAGTTACG CGTTAAACCAACTAGAA (SEQ ID NO: 500), AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT83 / 235B1195.70202WO00#14468377 v2TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCAC GGGTGTGGTACGCAGTCCTTTCGAGTACCAAATTAATCGCGGTTCTATCTAGTTA CGCGTTAAACCAACTAGAA (SEQ ID NO: 501), AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTGT GGTACGCAGTCCTTTCGAGTACCCGCGGTTCTATCTAGTTACGCGTTAAACCAAC TAGAA (SEQ ID NO: 502), AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGTG TGGTACGCAGTCCTTTCGAGTACCCGCGGTTCTATCTAGTTACGCGTTAAACCAA CTAGAA (SEQ ID NO: 503), AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT GTGGTACGCAGTCCTTTCGAGTACCCGCGGTTCTATCTAGTTACGCGTTAAACCA ACTAGAA (SEQ ID NO: 504), AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGCAGTCCTTTCGAGTACCCGCGGTTCTATCTAGTTACGCGTTAAAC CAACTAGAA (SEQ ID NO: 505), AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGCAGTCCTTTCGAGTACCCGCGGTTCTATCTAGTTACGCGTTAAA CCAACTAGAA (SEQ ID NO: 506), AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCAC GGGTGTGGTACGCAGTCCTTTCGAGTACCCGCGGTTCTATCTAGTTACGCGTTAA ACCAACTAGAA (SEQ ID NO: 507), AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTGT GGTACGCAGTCCTTTCGAGTACCCTTCTAATCCGCGGTTCTATCTAGTTACGCGTT AAACCAACTAGAA (SEQ ID NO: 508), AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT84 / 235B1195.70202WO00#14468377 v2GTGGTACGCAGTCCTTTCGAGTACCCTTTCCTAACGCGGTTCTATCTAGTTACGCG TTAAACCAACTAGAA (SEQ ID NO: 509), AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGCAGTCCTTTCGAGTACCCTGATTCAACGCGGTTCTATCTAGTTAC GCGTTAAACCAACTAGAA (SEQ ID NO: 510), AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGCAGTCCTTTCGAGTACCCTGAATTCCCGCGGTTCTATCTAGTTAC GCGTTAAACCAACTAGAA (SEQ ID NO: 511), AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCAC GGGTGTGGTACGCAGTCCTTTCGAGTACCCTTCCCATACGCGGTTCTATCTAGTTA CGCGTTAAACCAACTAGAA (SEQ ID NO: 512), AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTGT GGTACGCAGTCCTTTCGAGTACCCCGCGGTTCTATCTAGTTACGCGTTAAACCAA CTAGAA (SEQ ID NO: 513), AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGTG TGGTACGCAGTCCTTTCGAGTACCCCGCGGTTCTATCTAGTTACGCGTTAAACCA ACTAGAA (SEQ ID NO: 514), AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT GTGGTACGCAGTCCTTTCGAGTACCCCGCGGTTCTATCTAGTTACGCGTTAAACC AACTAGAA (SEQ ID NO: 515), AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGCAGTCCTTTCGAGTACCCCGCGGTTCTATCTAGTTACGCGTTAAA CCAACTAGAA (SEQ ID NO: 516), AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGCAGTCCTTTCGAGTACCCCGCGGTTCTATCTAGTTACGCGTTAA85 / 235B1195.70202WO00#14468377 v2ACCAACTAGAA (SEQ ID NO: 517), AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCAC GGGTGTGGTACGCAGTCCTTTCGAGTACCCCGCGGTTCTATCTAGTTACGCGTTA AACCAACTAGAA (SEQ ID NO: 518), AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTGT GGTACGCAGTCCTTTCGAGTACCCAATCCAAATCGCGGTTCTATCTAGTTACGCG TTAAACCAACTAGAA (SEQ ID NO: 519), AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGTG TGGTACGCAGTCCTTTCGAGTACCCAAATGAAGTCGCGGTTCTATCTAGTTACGC GTTAAACCAACTAGAA (SEQ ID NO: 520), AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT GTGGTACGCAGTCCTTTCGAGTACCCAATTCCGAACGCGGTTCTATCTAGTTACG CGTTAAACCAACTAGAA (SEQ ID NO: 521), AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGCAGTCCTTTCGAGTACCCAAATGAATACGCGGTTCTATCTAGTTA CGCGTTAAACCAACTAGAA (SEQ ID NO: 522), AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGCAGTCCTTTCGAGTACCCAAATTTAAGCGCGGTTCTATCTAGTT ACGCGTTAAACCAACTAGAA (SEQ ID NO: 523), AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCAC GGGTGTGGTACGCAGTCCTTTCGAGTACCCAAATAAAGACGCGGTTCTATCTAGT TACGCGTTAAACCAACTAGAA (SEQ ID NO: 524), AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTGT GGTACGCAGTCCTTTCGAGTACCCACGCGGTTCTATCTAGTTACGCGTTAAACCA ACTAGAA (SEQ ID NO: 525),86 / 235B1195.70202WO00#14468377 v2AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGTG TGGTACGCAGTCCTTTCGAGTACCCACGCGGTTCTATCTAGTTACGCGTTAAACC AACTAGAA (SEQ ID NO: 526), AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT GTGGTACGCAGTCCTTTCGAGTACCCACGCGGTTCTATCTAGTTACGCGTTAAAC CAACTAGAA (SEQ ID NO: 527), AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGCAGTCCTTTCGAGTACCCACGCGGTTCTATCTAGTTACGCGTTAA ACCAACTAGAA (SEQ ID NO: 528), AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGCAGTCCTTTCGAGTACCCACGCGGTTCTATCTAGTTACGCGTTA AACCAACTAGAA (SEQ ID NO: 529), AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCAC GGGTGTGGTACGCAGTCCTTTCGAGTACCCACGCGGTTCTATCTAGTTACGCGTT AAACCAACTAGAA (SEQ ID NO: 530), AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTGT GGTACGCAGTCCTTTCGAGTACCCACCTCCCGACCGCGGTTCTATCTAGTTACGC GTTAAACCAACTAGAA (SEQ ID NO: 531), AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT GTGGTACGCAGTCCTTTCGAGTACCCACTTCAATGACGCGGTTCTATCTAGTTAC GCGTTAAACCAACTAGAA (SEQ ID NO: 532), AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGCAGTCCTTTCGAGTACCCACTCATGAATCGCGGTTCTATCTAGTT ACGCGTTAAACCAACTAGAA (SEQ ID NO: 533), AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT87 / 235B1195.70202WO00#14468377 v2TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGCAGTCCTTTCGAGTACCCACTTCAATGACGCGGTTCTATCTAGT TACGCGTTAAACCAACTAGAA (SEQ ID NO: 534), AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCAC GGGTGTGGTACGCAGTCCTTTCGAGTACCCACTAATAAATCGCGGTTCTATCTAG TTACGCGTTAAACCAACTAGAA (SEQ ID NO: 535), AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTGT GGTACGCAGTCCTTTCGAGTACCCACCGCGGTTCTATCTAGTTACGCGTTAAACC AACTAGAA (SEQ ID NO: 536), AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGTG TGGTACGCAGTCCTTTCGAGTACCCACCGCGGTTCTATCTAGTTACGCGTTAAAC CAACTAGAA (SEQ ID NO: 537), AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT GTGGTACGCAGTCCTTTCGAGTACCCACCGCGGTTCTATCTAGTTACGCGTTAAA CCAACTAGAA (SEQ ID NO: 538), AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGCAGTCCTTTCGAGTACCCACCGCGGTTCTATCTAGTTACGCGTTA AACCAACTAGAA (SEQ ID NO: 539), AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGCAGTCCTTTCGAGTACCCACCGCGGTTCTATCTAGTTACGCGTT AAACCAACTAGAA (SEQ ID NO: 540), AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCAC GGGTGTGGTACGCAGTCCTTTCGAGTACCCACCGCGGTTCTATCTAGTTACGCGT TAAACCAACTAGAA (SEQ ID NO: 541), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTGT88 / 235B1195.70202WO00#14468377 v2GGTACGCAGTCCTTTCGAGTACCAATTAATTCGCGGTTCTATCTAGTTACGCGTTA AACCAACTAGAA (SEQ ID NO: 542), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGTG TGGTACGCAGTCCTTTCGAGTACCGTCTAAACCGCGGTTCTATCTAGTTACGCGTT AAACCAACTAGAA (SEQ ID NO: 543), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT GTGGTACGCAGTCCTTTCGAGTACCAATCTAAACGCGGTTCTATCTAGTTACGCG TTAAACCAACTAGAA (SEQ ID NO: 544), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGCAGTCCTTTCGAGTACCAAATTGATCGCGGTTCTATCTAGTTACG CGTTAAACCAACTAGAA (SEQ ID NO: 545), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGCAGTCCTTTCGAGTACCAGAAATGTCGCGGTTCTATCTAGTTAC GCGTTAAACCAACTAGAA (SEQ ID NO: 546), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCAC GGGTGTGGTACGCAGTCCTTTCGAGTACCGTCTGAAACGCGGTTCTATCTAGTTA CGCGTTAAACCAACTAGAA (SEQ ID NO: 547), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTGT GGTACGCAGTCCTTTCGAGTACCCGCGGTTCTATCTAGTTACGCGTTAAACCAAC TAGAA (SEQ ID NO: 548), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGTG TGGTACGCAGTCCTTTCGAGTACCCGCGGTTCTATCTAGTTACGCGTTAAACCAA CTAGAA (SEQ ID NO: 549), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT GTGGTACGCAGTCCTTTCGAGTACCCGCGGTTCTATCTAGTTACGCGTTAAACCA89 / 235B1195.70202WO00#14468377 v2ACTAGAA (SEQ ID NO: 550), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGCAGTCCTTTCGAGTACCCGCGGTTCTATCTAGTTACGCGTTAAAC CAACTAGAA (SEQ ID NO: 551), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGCAGTCCTTTCGAGTACCCGCGGTTCTATCTAGTTACGCGTTAAA CCAACTAGAA (SEQ ID NO: 552), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCAC GGGTGTGGTACGCAGTCCTTTCGAGTACCCGCGGTTCTATCTAGTTACGCGTTAA ACCAACTAGAA (SEQ ID NO: 553), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTGT GGTACGCAGTCCTTTCGAGTACCCTTTCATAACGCGGTTCTATCTAGTTACGCGTT AAACCAACTAGAA (SEQ ID NO: 554), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGTG TGGTACGCAGTCCTTTCGAGTACCCTGAATAAACGCGGTTCTATCTAGTTACGCG TTAAACCAACTAGAA (SEQ ID NO: 555), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT GTGGTACGCAGTCCTTTCGAGTACCCTGATAATACGCGGTTCTATCTAGTTACGC GTTAAACCAACTAGAA (SEQ ID NO: 556), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGCAGTCCTTTCGAGTACCCTGTTAAACCGCGGTTCTATCTAGTTAC GCGTTAAACCAACTAGAA (SEQ ID NO: 557), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGCAGTCCTTTCGAGTACCCTTCTCAAACGCGGTTCTATCTAGTTAC GCGTTAAACCAACTAGAA (SEQ ID NO: 558),90 / 235B1195.70202WO00#14468377 v2GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCAC GGGTGTGGTACGCAGTCCTTTCGAGTACCCTTCTAATACGCGGTTCTATCTAGTTA CGCGTTAAACCAACTAGAA (SEQ ID NO: 559), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTGT GGTACGCAGTCCTTTCGAGTACCCCGCGGTTCTATCTAGTTACGCGTTAAACCAA CTAGAA (SEQ ID NO: 560), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGTG TGGTACGCAGTCCTTTCGAGTACCCCGCGGTTCTATCTAGTTACGCGTTAAACCA ACTAGAA (SEQ ID NO: 561), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT GTGGTACGCAGTCCTTTCGAGTACCCCGCGGTTCTATCTAGTTACGCGTTAAACC AACTAGAA (SEQ ID NO: 562), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGCAGTCCTTTCGAGTACCCCGCGGTTCTATCTAGTTACGCGTTAAA CCAACTAGAA (SEQ ID NO: 563), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGCAGTCCTTTCGAGTACCCCGCGGTTCTATCTAGTTACGCGTTAA ACCAACTAGAA (SEQ ID NO: 564), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCAC GGGTGTGGTACGCAGTCCTTTCGAGTACCCCGCGGTTCTATCTAGTTACGCGTTA AACCAACTAGAA (SEQ ID NO: 565), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTGT GGTACGCAGTCCTTTCGAGTACCCAATAAAGAGCGCGGTTCTATCTAGTTACGCG TTAAACCAACTAGAA (SEQ ID NO: 566), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT91 / 235B1195.70202WO00#14468377 v2TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGTG TGGTACGCAGTCCTTTCGAGTACCCAAACTTAAACGCGGTTCTATCTAGTTACGC GTTAAACCAACTAGAA (SEQ ID NO: 567), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT GTGGTACGCAGTCCTTTCGAGTACCCAAATTGATACGCGGTTCTATCTAGTTACG CGTTAAACCAACTAGAA (SEQ ID NO: 568), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGCAGTCCTTTCGAGTACCCAATTAAAGTCGCGGTTCTATCTAGTTA CGCGTTAAACCAACTAGAA (SEQ ID NO: 569), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGCAGTCCTTTCGAGTACCCAAACGAAATCGCGGTTCTATCTAGTT ACGCGTTAAACCAACTAGAA (SEQ ID NO: 570), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCAC GGGTGTGGTACGCAGTCCTTTCGAGTACCCAATTAATAACGCGGTTCTATCTAGT TACGCGTTAAACCAACTAGAA (SEQ ID NO: 571), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTGT GGTACGCAGTCCTTTCGAGTACCCACGCGGTTCTATCTAGTTACGCGTTAAACCA ACTAGAA (SEQ ID NO: 572), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGTG TGGTACGCAGTCCTTTCGAGTACCCACGCGGTTCTATCTAGTTACGCGTTAAACC AACTAGAA (SEQ ID NO: 573), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT GTGGTACGCAGTCCTTTCGAGTACCCACGCGGTTCTATCTAGTTACGCGTTAAAC CAACTAGAA (SEQ ID NO: 574), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG92 / 235B1195.70202WO00#14468377 v2GTGTGGTACGCAGTCCTTTCGAGTACCCACGCGGTTCTATCTAGTTACGCGTTAA ACCAACTAGAA (SEQ ID NO: 575), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGCAGTCCTTTCGAGTACCCACGCGGTTCTATCTAGTTACGCGTTA AACCAACTAGAA (SEQ ID NO: 576), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCAC GGGTGTGGTACGCAGTCCTTTCGAGTACCCACGCGGTTCTATCTAGTTACGCGTT AAACCAACTAGAA (SEQ ID NO: 577), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTGT GGTACGCAGTCCTTTCGAGTACCCACTTCAATATCGCGGTTCTATCTAGTTACGC GTTAAACCAACTAGAA (SEQ ID NO: 578), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGTG TGGTACGCAGTCCTTTCGAGTACCCACTCATAGAGCGCGGTTCTATCTAGTTACG CGTTAAACCAACTAGAA (SEQ ID NO: 579), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT GTGGTACGCAGTCCTTTCGAGTACCCACCTTTAAACCGCGGTTCTATCTAGTTAC GCGTTAAACCAACTAGAA (SEQ ID NO: 580), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGCAGTCCTTTCGAGTACCCACTCTTTAAACGCGGTTCTATCTAGTTA CGCGTTAAACCAACTAGAA (SEQ ID NO: 581), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGCAGTCCTTTCGAGTACCCACTAAAGAATCGCGGTTCTATCTAGT TACGCGTTAAACCAACTAGAA (SEQ ID NO: 582), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCAC GGGTGTGGTACGCAGTCCTTTCGAGTACCCACTCTTAAATCGCGGTTCTATCTAG93 / 235B1195.70202WO00#14468377 v2TTACGCGTTAAACCAACTAGAA (SEQ ID NO: 583), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTGT GGTACGCAGTCCTTTCGAGTACCCACCGCGGTTCTATCTAGTTACGCGTTAAACC AACTAGAA (SEQ ID NO: 584), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGTG TGGTACGCAGTCCTTTCGAGTACCCACCGCGGTTCTATCTAGTTACGCGTTAAAC CAACTAGAA (SEQ ID NO: 585), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT GTGGTACGCAGTCCTTTCGAGTACCCACCGCGGTTCTATCTAGTTACGCGTTAAA CCAACTAGAA (SEQ ID NO: 586), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGCAGTCCTTTCGAGTACCCACCGCGGTTCTATCTAGTTACGCGTTA AACCAACTAGAA (SEQ ID NO: 587), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGCAGTCCTTTCGAGTACCCACCGCGGTTCTATCTAGTTACGCGTT AAACCAACTAGAA (SEQ ID NO: 588), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCAC GGGTGTGGTACGCAGTCCTTTCGAGTACCCACCGCGGTTCTATCTAGTTACGCGT TAAACCAACTAGAA (SEQ ID NO: 589), AGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTGT GGTACGCAGTCCTTTCGAGTACCGTCTTCCACGCGGTTCTATCTAGTTACGCGTTA AACCAACTAGAA (SEQ ID NO: 590), AGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGT GTGGTACGCAGTCCTTTCGAGTACCAAATCCTACGCGGTTCTATCTAGTTACGCG TTAAACCAACTAGAA (SEQ ID NO: 591),94 / 235B1195.70202WO00#14468377 v2AGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG TGTGGTACGCAGTCCTTTCGAGTACCGTTAACCGCGCGGTTCTATCTAGTTACGC GTTAAACCAACTAGAA (SEQ ID NO: 592), AGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGCAGTCCTTTCGAGTACCGTCTCCTCCGCGGTTCTATCTAGTTACGC GTTAAACCAACTAGAA (SEQ ID NO: 593), AGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGCAGTCCTTTCGAGTACCAAATCTTCCGCGGTTCTATCTAGTTAC GCGTTAAACCAACTAGAA (SEQ ID NO: 594), AGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCAC GGGTGTGGTACGCAGTCCTTTCGAGTACCGTTAAATACGCGGTTCTATCTAGTTA CGCGTTAAACCAACTAGAA (SEQ ID NO: 595), AGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTGT GGTACGCAGTCCTTTCGAGTACCCGCGGTTCTATCTAGTTACGCGTTAAACCAAC TAGAA (SEQ ID NO: 596), AGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGT GTGGTACGCAGTCCTTTCGAGTACCCGCGGTTCTATCTAGTTACGCGTTAAACCA ACTAGAA (SEQ ID NO: 597), AGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG TGTGGTACGCAGTCCTTTCGAGTACCCGCGGTTCTATCTAGTTACGCGTTAAACC AACTAGAA (SEQ ID NO: 598), AGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGCAGTCCTTTCGAGTACCCGCGGTTCTATCTAGTTACGCGTTAAAC CAACTAGAA (SEQ ID NO: 599), AGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT95 / 235B1195.70202WO00#14468377 v2TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGCAGTCCTTTCGAGTACCCGCGGTTCTATCTAGTTACGCGTTAAA CCAACTAGAA (SEQ ID NO: 600), AGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCAC GGGTGTGGTACGCAGTCCTTTCGAGTACCCGCGGTTCTATCTAGTTACGCGTTAA ACCAACTAGAA (SEQ ID NO: 601), AGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTGT GGTACGCAGTCCTTTCGAGTACCCTTCTAATCCGCGGTTCTATCTAGTTACGCGTT AAACCAACTAGAA (SEQ ID NO: 602), AGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGT GTGGTACGCAGTCCTTTCGAGTACCCTGAATCCACGCGGTTCTATCTAGTTACGC GTTAAACCAACTAGAA (SEQ ID NO: 603), AGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG TGTGGTACGCAGTCCTTTCGAGTACCCTTTCCTAACGCGGTTCTATCTAGTTACGC GTTAAACCAACTAGAA (SEQ ID NO: 604), AGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGCAGTCCTTTCGAGTACCCTGATTCAACGCGGTTCTATCTAGTTAC GCGTTAAACCAACTAGAA (SEQ ID NO: 605), AGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGCAGTCCTTTCGAGTACCCTGAATTCCCGCGGTTCTATCTAGTTAC GCGTTAAACCAACTAGAA (SEQ ID NO: 606), AGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCAC GGGTGTGGTACGCAGTCCTTTCGAGTACCCTTCCCATACGCGGTTCTATCTAGTTA CGCGTTAAACCAACTAGAA (SEQ ID NO: 607), AGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTGT96 / 235B1195.70202WO00#14468377 v2GGTACGCAGTCCTTTCGAGTACCCCGCGGTTCTATCTAGTTACGCGTTAAACCAA CTAGAA (SEQ ID NO: 608), AGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGT GTGGTACGCAGTCCTTTCGAGTACCCCGCGGTTCTATCTAGTTACGCGTTAAACC AACTAGAA (SEQ ID NO: 609), AGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG TGTGGTACGCAGTCCTTTCGAGTACCCCGCGGTTCTATCTAGTTACGCGTTAAACCAACTAGAA (SEQ ID NO: 610), AGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGCAGTCCTTTCGAGTACCCCGCGGTTCTATCTAGTTACGCGTTAAA CCAACTAGAA (SEQ ID NO: 611), AGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGCAGTCCTTTCGAGTACCCCGCGGTTCTATCTAGTTACGCGTTAA ACCAACTAGAA (SEQ ID NO: 612), AGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCAC GGGTGTGGTACGCAGTCCTTTCGAGTACCCCGCGGTTCTATCTAGTTACGCGTTA AACCAACTAGAA (SEQ ID NO: 613), AGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTGT GGTACGCAGTCCTTTCGAGTACCCAATCCAAATCGCGGTTCTATCTAGTTACGCG TTAAACCAACTAGAA (SEQ ID NO: 614), AGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGT GTGGTACGCAGTCCTTTCGAGTACCCAAATGAAGTCGCGGTTCTATCTAGTTACG CGTTAAACCAACTAGAA (SEQ ID NO: 615), AGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG TGTGGTACGCAGTCCTTTCGAGTACCCAATTCCGAACGCGGTTCTATCTAGTTAC97 / 235B1195.70202WO00#14468377 v2GCGTTAAACCAACTAGAA (SEQ ID NO: 616), AGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGCAGTCCTTTCGAGTACCCAAATGAATACGCGGTTCTATCTAGTTA CGCGTTAAACCAACTAGAA (SEQ ID NO: 617), AGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGCAGTCCTTTCGAGTACCCAAATTTAAGCGCGGTTCTATCTAGTT ACGCGTTAAACCAACTAGAA (SEQ ID NO: 618), AGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCAC GGGTGTGGTACGCAGTCCTTTCGAGTACCCAAATAAAGACGCGGTTCTATCTAGT TACGCGTTAAACCAACTAGAA (SEQ ID NO: 619), AGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTGT GGTACGCAGTCCTTTCGAGTACCCACGCGGTTCTATCTAGTTACGCGTTAAACCA ACTAGAA (SEQ ID NO: 620), AGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGT GTGGTACGCAGTCCTTTCGAGTACCCACGCGGTTCTATCTAGTTACGCGTTAAAC CAACTAGAA (SEQ ID NO: 621), AGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG TGTGGTACGCAGTCCTTTCGAGTACCCACGCGGTTCTATCTAGTTACGCGTTAAA CCAACTAGAA (SEQ ID NO: 622), AGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGCAGTCCTTTCGAGTACCCACGCGGTTCTATCTAGTTACGCGTTAA ACCAACTAGAA (SEQ ID NO: 623), AGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGCAGTCCTTTCGAGTACCCACGCGGTTCTATCTAGTTACGCGTTA AACCAACTAGAA (SEQ ID NO: 624),98 / 235B1195.70202WO00#14468377 v2AGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCAC GGGTGTGGTACGCAGTCCTTTCGAGTACCCACGCGGTTCTATCTAGTTACGCGTT AAACCAACTAGAA (SEQ ID NO: 625), AGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTGT GGTACGCAGTCCTTTCGAGTACCCACCTCCCGACCGCGGTTCTATCTAGTTACGC GTTAAACCAACTAGAA (SEQ ID NO: 626), AGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGT GTGGTACGCAGTCCTTTCGAGTACCCACTCCAAGAGCGCGGTTCTATCTAGTTAC GCGTTAAACCAACTAGAA (SEQ ID NO: 627), AGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG TGTGGTACGCAGTCCTTTCGAGTACCCACTTCAATGACGCGGTTCTATCTAGTTAC GCGTTAAACCAACTAGAA (SEQ ID NO: 628), AGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGCAGTCCTTTCGAGTACCCACTCATGAATCGCGGTTCTATCTAGTT ACGCGTTAAACCAACTAGAA (SEQ ID NO: 629), AGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGCAGTCCTTTCGAGTACCCACTTCAATGACGCGGTTCTATCTAGT TACGCGTTAAACCAACTAGAA (SEQ ID NO: 630), AGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCAC GGGTGTGGTACGCAGTCCTTTCGAGTACCCACTAATAAATCGCGGTTCTATCTAG TTACGCGTTAAACCAACTAGAA (SEQ ID NO: 631), AGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTGT GGTACGCAGTCCTTTCGAGTACCCACCGCGGTTCTATCTAGTTACGCGTTAAACC AACTAGAA (SEQ ID NO: 632), AGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT99 / 235B1195.70202WO00#14468377 v2TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGT GTGGTACGCAGTCCTTTCGAGTACCCACCGCGGTTCTATCTAGTTACGCGTTAAA CCAACTAGAA (SEQ ID NO: 633), AGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG TGTGGTACGCAGTCCTTTCGAGTACCCACCGCGGTTCTATCTAGTTACGCGTTAA ACCAACTAGAA (SEQ ID NO: 634), AGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGCAGTCCTTTCGAGTACCCACCGCGGTTCTATCTAGTTACGCGTTA AACCAACTAGAA (SEQ ID NO: 635), AGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGCAGTCCTTTCGAGTACCCACCGCGGTTCTATCTAGTTACGCGTT AAACCAACTAGAA (SEQ ID NO: 636), AGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCAC GGGTGTGGTACGCAGTCCTTTCGAGTACCCACCGCGGTTCTATCTAGTTACGCGT TAAACCAACTAGAA (SEQ ID NO: 637), GGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTGT GGTACGCAGTCCTTTCGAGTACCAATTAATTCGCGGTTCTATCTAGTTACGCGTTA AACCAACTAGAA (SEQ ID NO: 638), GGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGT GTGGTACGCAGTCCTTTCGAGTACCGTCTAAACCGCGGTTCTATCTAGTTACGCG TTAAACCAACTAGAA (SEQ ID NO: 639), GGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG TGTGGTACGCAGTCCTTTCGAGTACCGTCTTAACCGCGGTTCTATCTAGTTACGCG TTAAACCAACTAGAA (SEQ ID NO: 640), GGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG100 / 235B1195.70202WO00#14468377 v2GTGTGGTACGCAGTCCTTTCGAGTACCGTTCTAAACGCGGTTCTATCTAGTTACG CGTTAAACCAACTAGAA (SEQ ID NO: 641), GGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGCAGTCCTTTCGAGTACCAGAAATGTCGCGGTTCTATCTAGTTAC GCGTTAAACCAACTAGAA (SEQ ID NO: 642), GGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCAC GGGTGTGGTACGCAGTCCTTTCGAGTACCAATCTTAACGCGGTTCTATCTAGTTA CGCGTTAAACCAACTAGAA (SEQ ID NO: 643), GGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTGT GGTACGCAGTCCTTTCGAGTACCCGCGGTTCTATCTAGTTACGCGTTAAACCAAC TAGAA (SEQ ID NO: 644), GGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGT GTGGTACGCAGTCCTTTCGAGTACCCGCGGTTCTATCTAGTTACGCGTTAAACCA ACTAGAA (SEQ ID NO: 645), GGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG TGTGGTACGCAGTCCTTTCGAGTACCCGCGGTTCTATCTAGTTACGCGTTAAACC AACTAGAA (SEQ ID NO: 646), GGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGCAGTCCTTTCGAGTACCCGCGGTTCTATCTAGTTACGCGTTAAAC CAACTAGAA (SEQ ID NO: 647), GGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGCAGTCCTTTCGAGTACCCGCGGTTCTATCTAGTTACGCGTTAAA CCAACTAGAA (SEQ ID NO: 648), GGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCAC GGGTGTGGTACGCAGTCCTTTCGAGTACCCGCGGTTCTATCTAGTTACGCGTTAA101 / 235B1195.70202WO00#14468377 v2ACCAACTAGAA (SEQ ID NO: 649), GGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTGT GGTACGCAGTCCTTTCGAGTACCCTTTCATAACGCGGTTCTATCTAGTTACGCGTT AAACCAACTAGAA (SEQ ID NO: 650), GGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGT GTGGTACGCAGTCCTTTCGAGTACCCTGAATAAACGCGGTTCTATCTAGTTACGC GTTAAACCAACTAGAA (SEQ ID NO: 651), GGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG TGTGGTACGCAGTCCTTTCGAGTACCCTGATAATACGCGGTTCTATCTAGTTACG CGTTAAACCAACTAGAA (SEQ ID NO: 652), GGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGCAGTCCTTTCGAGTACCCTGTTAAACCGCGGTTCTATCTAGTTAC GCGTTAAACCAACTAGAA (SEQ ID NO: 653), GGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGCAGTCCTTTCGAGTACCCTTCTCAAACGCGGTTCTATCTAGTTAC GCGTTAAACCAACTAGAA (SEQ ID NO: 654), GGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCAC GGGTGTGGTACGCAGTCCTTTCGAGTACCCTTCTAATACGCGGTTCTATCTAGTTA CGCGTTAAACCAACTAGAA (SEQ ID NO: 655), GGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTGT GGTACGCAGTCCTTTCGAGTACCCCGCGGTTCTATCTAGTTACGCGTTAAACCAA CTAGAA (SEQ ID NO: 656), GGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGT GTGGTACGCAGTCCTTTCGAGTACCCCGCGGTTCTATCTAGTTACGCGTTAAACC AACTAGAA (SEQ ID NO: 657),102 / 235B1195.70202WO00#14468377 v2GGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG TGTGGTACGCAGTCCTTTCGAGTACCCCGCGGTTCTATCTAGTTACGCGTTAAAC CAACTAGAA (SEQ ID NO: 658), GGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGCAGTCCTTTCGAGTACCCCGCGGTTCTATCTAGTTACGCGTTAAA CCAACTAGAA (SEQ ID NO: 659), GGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGCAGTCCTTTCGAGTACCCCGCGGTTCTATCTAGTTACGCGTTAA ACCAACTAGAA (SEQ ID NO: 660), GGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCAC GGGTGTGGTACGCAGTCCTTTCGAGTACCCCGCGGTTCTATCTAGTTACGCGTTA AACCAACTAGAA (SEQ ID NO: 661), GGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTGT GGTACGCAGTCCTTTCGAGTACCCAATAAAGAGCGCGGTTCTATCTAGTTACGCG TTAAACCAACTAGAA (SEQ ID NO: 662), GGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGT GTGGTACGCAGTCCTTTCGAGTACCCAAACTTAAACGCGGTTCTATCTAGTTACG CGTTAAACCAACTAGAA (SEQ ID NO: 663), GGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG TGTGGTACGCAGTCCTTTCGAGTACCCAAATTGATACGCGGTTCTATCTAGTTAC GCGTTAAACCAACTAGAA (SEQ ID NO: 664), GGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGCAGTCCTTTCGAGTACCCAATTAAAGTCGCGGTTCTATCTAGTTA CGCGTTAAACCAACTAGAA (SEQ ID NO: 665), GGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT103 / 235B1195.70202WO00#14468377 v2TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGCAGTCCTTTCGAGTACCCAAACGAAATCGCGGTTCTATCTAGTT ACGCGTTAAACCAACTAGAA (SEQ ID NO: 666), GGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCAC GGGTGTGGTACGCAGTCCTTTCGAGTACCCAATTAATAACGCGGTTCTATCTAGT TACGCGTTAAACCAACTAGAA (SEQ ID NO: 667), GGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTGT GGTACGCAGTCCTTTCGAGTACCCACGCGGTTCTATCTAGTTACGCGTTAAACCA ACTAGAA (SEQ ID NO: 668), GGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGT GTGGTACGCAGTCCTTTCGAGTACCCACGCGGTTCTATCTAGTTACGCGTTAAAC CAACTAGAA (SEQ ID NO: 669), GGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG TGTGGTACGCAGTCCTTTCGAGTACCCACGCGGTTCTATCTAGTTACGCGTTAAA CCAACTAGAA (SEQ ID NO: 670), GGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGCAGTCCTTTCGAGTACCCACGCGGTTCTATCTAGTTACGCGTTAA ACCAACTAGAA (SEQ ID NO: 671), GGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGCAGTCCTTTCGAGTACCCACGCGGTTCTATCTAGTTACGCGTTA AACCAACTAGAA (SEQ ID NO: 672), GGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCAC GGGTGTGGTACGCAGTCCTTTCGAGTACCCACGCGGTTCTATCTAGTTACGCGTT AAACCAACTAGAA (SEQ ID NO: 673), GGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTGT104 / 235B1195.70202WO00#14468377 v2GGTACGCAGTCCTTTCGAGTACCCACTTCAATATCGCGGTTCTATCTAGTTACGC GTTAAACCAACTAGAA (SEQ ID NO: 674), GGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGT GTGGTACGCAGTCCTTTCGAGTACCCACTCATAGAGCGCGGTTCTATCTAGTTAC GCGTTAAACCAACTAGAA (SEQ ID NO: 675), GGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG TGTGGTACGCAGTCCTTTCGAGTACCCACCTTTAAACCGCGGTTCTATCTAGTTAC GCGTTAAACCAACTAGAA (SEQ ID NO: 676), GGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGCAGTCCTTTCGAGTACCCACTCTTTAAACGCGGTTCTATCTAGTTA CGCGTTAAACCAACTAGAA (SEQ ID NO: 677), GGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGCAGTCCTTTCGAGTACCCACTAAAGAATCGCGGTTCTATCTAGT TACGCGTTAAACCAACTAGAA (SEQ ID NO: 678), GGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCAC GGGTGTGGTACGCAGTCCTTTCGAGTACCCACTCTTAAATCGCGGTTCTATCTAG TTACGCGTTAAACCAACTAGAA (SEQ ID NO: 679), GGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTGT GGTACGCAGTCCTTTCGAGTACCCACCGCGGTTCTATCTAGTTACGCGTTAAACC AACTAGAA (SEQ ID NO: 680), GGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGT GTGGTACGCAGTCCTTTCGAGTACCCACCGCGGTTCTATCTAGTTACGCGTTAAA CCAACTAGAA (SEQ ID NO: 681), GGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG TGTGGTACGCAGTCCTTTCGAGTACCCACCGCGGTTCTATCTAGTTACGCGTTAA105 / 235B1195.70202WO00#14468377 v2ACCAACTAGAA (SEQ ID NO: 682), GGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGCAGTCCTTTCGAGTACCCACCGCGGTTCTATCTAGTTACGCGTTA AACCAACTAGAA (SEQ ID NO: 683), GGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGCAGTCCTTTCGAGTACCCACCGCGGTTCTATCTAGTTACGCGTT AAACCAACTAGAA (SEQ ID NO: 684), GGTACTGTGGGTACTCGAAGGTTTGAGAGCTATGCTGGAAACAGCATAGCAAGT TCAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCAC GGGTGTGGTACGCAGTCCTTTCGAGTACCCACCGCGGTTCTATCTAGTTACGCGT TAAACCAACTAGAA (SEQ ID NO: 685), AGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTGT GGTACGCAGTCCTTTCGAGTACCAAATCCTGCGCGGTTCTATCTAGTTACGCGTT AAACCAACTAGAA (SEQ ID NO: 686), AGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGT GTGGTACGCAGTCCTTTCGAGTACCAAATCCTACGCGGTTCTATCTAGTTACGCG TTAAACCAACTAGAA (SEQ ID NO: 687), AGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG TGTGGTACGCAGTCCTTTCGAGTACCGTTAACCGCGCGGTTCTATCTAGTTACGC GTTAAACCAACTAGAA (SEQ ID NO: 688), AGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGCAGTCCTTTCGAGTACCGTCTCCTCCGCGGTTCTATCTAGTTACGC GTTAAACCAACTAGAA (SEQ ID NO: 689), AGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGCAGTCCTTTCGAGTACCAATCCCTTCGCGGTTCTATCTAGTTACG CGTTAAACCAACTAGAA (SEQ ID NO: 690),106 / 235B1195.70202WO00#14468377 v2AGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCAC GGGTGTGGTACGCAGTCCTTTCGAGTACCAGACCCGTCGCGGTTCTATCTAGTTA CGCGTTAAACCAACTAGAA (SEQ ID NO: 691), AGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTGT GGTACGCAGTCCTTTCGAGTACCCGCGGTTCTATCTAGTTACGCGTTAAACCAAC TAGAA (SEQ ID NO: 692), AGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGT GTGGTACGCAGTCCTTTCGAGTACCCGCGGTTCTATCTAGTTACGCGTTAAACCA ACTAGAA (SEQ ID NO: 693), AGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG TGTGGTACGCAGTCCTTTCGAGTACCCGCGGTTCTATCTAGTTACGCGTTAAACC AACTAGAA (SEQ ID NO: 694), AGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGCAGTCCTTTCGAGTACCCGCGGTTCTATCTAGTTACGCGTTAAAC CAACTAGAA (SEQ ID NO: 695), AGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGCAGTCCTTTCGAGTACCCGCGGTTCTATCTAGTTACGCGTTAAA CCAACTAGAA (SEQ ID NO: 696), AGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCAC GGGTGTGGTACGCAGTCCTTTCGAGTACCCGCGGTTCTATCTAGTTACGCGTTAA ACCAACTAGAA (SEQ ID NO: 697), AGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTGT GGTACGCAGTCCTTTCGAGTACCCTTCTAATCCGCGGTTCTATCTAGTTACGCGTT AAACCAACTAGAA (SEQ ID NO: 698), AGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT107 / 235B1195.70202WO00#14468377 v2TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGT GTGGTACGCAGTCCTTTCGAGTACCCTGAATCCACGCGGTTCTATCTAGTTACGC GTTAAACCAACTAGAA (SEQ ID NO: 699), AGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG TGTGGTACGCAGTCCTTTCGAGTACCCTTTCCTAACGCGGTTCTATCTAGTTACGC GTTAAACCAACTAGAA (SEQ ID NO: 700), AGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGCAGTCCTTTCGAGTACCCTGATTCAACGCGGTTCTATCTAGTTAC GCGTTAAACCAACTAGAA (SEQ ID NO: 701), AGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGCAGTCCTTTCGAGTACCCTGAATTCCCGCGGTTCTATCTAGTTAC GCGTTAAACCAACTAGAA (SEQ ID NO: 702), AGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCAC GGGTGTGGTACGCAGTCCTTTCGAGTACCCTTCCCATACGCGGTTCTATCTAGTTA CGCGTTAAACCAACTAGAA (SEQ ID NO: 703), AGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTGT GGTACGCAGTCCTTTCGAGTACCCCGCGGTTCTATCTAGTTACGCGTTAAACCAA CTAGAA (SEQ ID NO: 704), AGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGT GTGGTACGCAGTCCTTTCGAGTACCCCGCGGTTCTATCTAGTTACGCGTTAAACC AACTAGAA (SEQ ID NO: 705), AGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG TGTGGTACGCAGTCCTTTCGAGTACCCCGCGGTTCTATCTAGTTACGCGTTAAAC CAACTAGAA (SEQ ID NO: 706), AGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG108 / 235B1195.70202WO00#14468377 v2GTGTGGTACGCAGTCCTTTCGAGTACCCCGCGGTTCTATCTAGTTACGCGTTAAA CCAACTAGAA (SEQ ID NO: 707), AGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGCAGTCCTTTCGAGTACCCCGCGGTTCTATCTAGTTACGCGTTAA ACCAACTAGAA (SEQ ID NO: 708), AGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCAC GGGTGTGGTACGCAGTCCTTTCGAGTACCCCGCGGTTCTATCTAGTTACGCGTTA AACCAACTAGAA (SEQ ID NO: 709), AGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTGT GGTACGCAGTCCTTTCGAGTACCCAATCCAAATCGCGGTTCTATCTAGTTACGCG TTAAACCAACTAGAA (SEQ ID NO: 710), AGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGT GTGGTACGCAGTCCTTTCGAGTACCCAAATGAAGTCGCGGTTCTATCTAGTTACG CGTTAAACCAACTAGAA (SEQ ID NO: 711), AGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG TGTGGTACGCAGTCCTTTCGAGTACCCAATTCCGAACGCGGTTCTATCTAGTTAC GCGTTAAACCAACTAGAA (SEQ ID NO: 712), AGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGCAGTCCTTTCGAGTACCCAAATGAATACGCGGTTCTATCTAGTTA CGCGTTAAACCAACTAGAA (SEQ ID NO: 713), AGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGCAGTCCTTTCGAGTACCCAAATTTAAGCGCGGTTCTATCTAGTT ACGCGTTAAACCAACTAGAA (SEQ ID NO: 714), AGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCAC GGGTGTGGTACGCAGTCCTTTCGAGTACCCAAATAAAGACGCGGTTCTATCTAGT109 / 235B1195.70202WO00#14468377 v2TACGCGTTAAACCAACTAGAA (SEQ ID NO: 715), AGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTGT GGTACGCAGTCCTTTCGAGTACCCACGCGGTTCTATCTAGTTACGCGTTAAACCA ACTAGAA (SEQ ID NO: 716), AGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGT GTGGTACGCAGTCCTTTCGAGTACCCACGCGGTTCTATCTAGTTACGCGTTAAAC CAACTAGAA (SEQ ID NO: 717), AGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG TGTGGTACGCAGTCCTTTCGAGTACCCACGCGGTTCTATCTAGTTACGCGTTAAA CCAACTAGAA (SEQ ID NO: 718), AGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGCAGTCCTTTCGAGTACCCACGCGGTTCTATCTAGTTACGCGTTAA ACCAACTAGAA (SEQ ID NO: 719), AGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGCAGTCCTTTCGAGTACCCACGCGGTTCTATCTAGTTACGCGTTA AACCAACTAGAA (SEQ ID NO: 720), AGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCAC GGGTGTGGTACGCAGTCCTTTCGAGTACCCACGCGGTTCTATCTAGTTACGCGTT AAACCAACTAGAA (SEQ ID NO: 721), AGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTGT GGTACGCAGTCCTTTCGAGTACCCACCTCCCGACCGCGGTTCTATCTAGTTACGC GTTAAACCAACTAGAA (SEQ ID NO: 722), AGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGT GTGGTACGCAGTCCTTTCGAGTACCCACTCCAAGAGCGCGGTTCTATCTAGTTAC GCGTTAAACCAACTAGAA (SEQ ID NO: 723),110 / 235B1195.70202WO00#14468377 v2AGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG TGTGGTACGCAGTCCTTTCGAGTACCCACTTCAATGACGCGGTTCTATCTAGTTAC GCGTTAAACCAACTAGAA (SEQ ID NO: 724), AGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGCAGTCCTTTCGAGTACCCACTCATGAATCGCGGTTCTATCTAGTT ACGCGTTAAACCAACTAGAA (SEQ ID NO: 725), AGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGCAGTCCTTTCGAGTACCCACTTCAATGACGCGGTTCTATCTAGT TACGCGTTAAACCAACTAGAA (SEQ ID NO: 726), AGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCAC GGGTGTGGTACGCAGTCCTTTCGAGTACCCACTAATAAATCGCGGTTCTATCTAG TTACGCGTTAAACCAACTAGAA (SEQ ID NO: 727), AGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTGT GGTACGCAGTCCTTTCGAGTACCCACCGCGGTTCTATCTAGTTACGCGTTAAACC AACTAGAA (SEQ ID NO: 728), AGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGT GTGGTACGCAGTCCTTTCGAGTACCCACCGCGGTTCTATCTAGTTACGCGTTAAA CCAACTAGAA (SEQ ID NO: 729), AGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG TGTGGTACGCAGTCCTTTCGAGTACCCACCGCGGTTCTATCTAGTTACGCGTTAA ACCAACTAGAA (SEQ ID NO: 730), AGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGCAGTCCTTTCGAGTACCCACCGCGGTTCTATCTAGTTACGCGTTA AACCAACTAGAA (SEQ ID NO: 731), AGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT111 / 235B1195.70202WO00#14468377 v2TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGCAGTCCTTTCGAGTACCCACCGCGGTTCTATCTAGTTACGCGTT AAACCAACTAGAA (SEQ ID NO: 732), AGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCAC GGGTGTGGTACGCAGTCCTTTCGAGTACCCACCGCGGTTCTATCTAGTTACGCGT TAAACCAACTAGAA (SEQ ID NO: 733), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTGT GGTACGCAGTCCTTTCGAGTACCAGAAATTTCGCGGTTCTATCTAGTTACGCGTT AAACCAACTAGAA (SEQ ID NO: 734), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGT GTGGTACGCAGTCCTTTCGAGTACCAGAAATTGCGCGGTTCTATCTAGTTACGCG TTAAACCAACTAGAA (SEQ ID NO: 735), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG TGTGGTACGCAGTCCTTTCGAGTACCAATCTAAACGCGGTTCTATCTAGTTACGC GTTAAACCAACTAGAA (SEQ ID NO: 736), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGCAGTCCTTTCGAGTACCAAATTGATCGCGGTTCTATCTAGTTACG CGTTAAACCAACTAGAA (SEQ ID NO: 737), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGCAGTCCTTTCGAGTACCAGAAATGTCGCGGTTCTATCTAGTTAC GCGTTAAACCAACTAGAA (SEQ ID NO: 738), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCAC GGGTGTGGTACGCAGTCCTTTCGAGTACCAATTAATGCGCGGTTCTATCTAGTTA CGCGTTAAACCAACTAGAA (SEQ ID NO: 739), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTGT112 / 235B1195.70202WO00#14468377 v2GGTACGCAGTCCTTTCGAGTACCCGCGGTTCTATCTAGTTACGCGTTAAACCAAC TAGAA (SEQ ID NO: 740), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGT GTGGTACGCAGTCCTTTCGAGTACCCGCGGTTCTATCTAGTTACGCGTTAAACCA ACTAGAA (SEQ ID NO: 741), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG TGTGGTACGCAGTCCTTTCGAGTACCCGCGGTTCTATCTAGTTACGCGTTAAACC AACTAGAA (SEQ ID NO: 742), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGCAGTCCTTTCGAGTACCCGCGGTTCTATCTAGTTACGCGTTAAAC CAACTAGAA (SEQ ID NO: 743), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGCAGTCCTTTCGAGTACCCGCGGTTCTATCTAGTTACGCGTTAAA CCAACTAGAA (SEQ ID NO: 744), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCAC GGGTGTGGTACGCAGTCCTTTCGAGTACCCGCGGTTCTATCTAGTTACGCGTTAA ACCAACTAGAA (SEQ ID NO: 745), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTGT GGTACGCAGTCCTTTCGAGTACCCTTTCATAACGCGGTTCTATCTAGTTACGCGTT AAACCAACTAGAA (SEQ ID NO: 746), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGT GTGGTACGCAGTCCTTTCGAGTACCCTGAATAAACGCGGTTCTATCTAGTTACGC GTTAAACCAACTAGAA (SEQ ID NO: 747), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG TGTGGTACGCAGTCCTTTCGAGTACCCTGATAATACGCGGTTCTATCTAGTTACG113 / 235B1195.70202WO00#14468377 v2CGTTAAACCAACTAGAA (SEQ ID NO: 748), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGCAGTCCTTTCGAGTACCCTGTTAAACCGCGGTTCTATCTAGTTAC GCGTTAAACCAACTAGAA (SEQ ID NO: 749), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGCAGTCCTTTCGAGTACCCTTCTCAAACGCGGTTCTATCTAGTTAC GCGTTAAACCAACTAGAA (SEQ ID NO: 750), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCAC GGGTGTGGTACGCAGTCCTTTCGAGTACCCTTCTAATACGCGGTTCTATCTAGTTA CGCGTTAAACCAACTAGAA (SEQ ID NO: 751), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTGT GGTACGCAGTCCTTTCGAGTACCCCGCGGTTCTATCTAGTTACGCGTTAAACCAA CTAGAA (SEQ ID NO: 752), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGT GTGGTACGCAGTCCTTTCGAGTACCCCGCGGTTCTATCTAGTTACGCGTTAAACC AACTAGAA (SEQ ID NO: 753), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG TGTGGTACGCAGTCCTTTCGAGTACCCCGCGGTTCTATCTAGTTACGCGTTAAAC CAACTAGAA (SEQ ID NO: 754), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGCAGTCCTTTCGAGTACCCCGCGGTTCTATCTAGTTACGCGTTAAA CCAACTAGAA (SEQ ID NO: 755), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGCAGTCCTTTCGAGTACCCCGCGGTTCTATCTAGTTACGCGTTAA ACCAACTAGAA (SEQ ID NO: 756),114 / 235B1195.70202WO00#14468377 v2GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCAC GGGTGTGGTACGCAGTCCTTTCGAGTACCCCGCGGTTCTATCTAGTTACGCGTTA AACCAACTAGAA (SEQ ID NO: 757), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTGT GGTACGCAGTCCTTTCGAGTACCCAATAAAGAGCGCGGTTCTATCTAGTTACGCG TTAAACCAACTAGAA (SEQ ID NO: 758), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGT GTGGTACGCAGTCCTTTCGAGTACCCAAACTTAAACGCGGTTCTATCTAGTTACG CGTTAAACCAACTAGAA (SEQ ID NO: 759), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG TGTGGTACGCAGTCCTTTCGAGTACCCAAATTGATACGCGGTTCTATCTAGTTAC GCGTTAAACCAACTAGAA (SEQ ID NO: 760), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGCAGTCCTTTCGAGTACCCAATTAAAGTCGCGGTTCTATCTAGTTA CGCGTTAAACCAACTAGAA (SEQ ID NO: 761), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGCAGTCCTTTCGAGTACCCAAACGAAATCGCGGTTCTATCTAGTT ACGCGTTAAACCAACTAGAA (SEQ ID NO: 762), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCAC GGGTGTGGTACGCAGTCCTTTCGAGTACCCAATTAATAACGCGGTTCTATCTAGT TACGCGTTAAACCAACTAGAA (SEQ ID NO: 763), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTGT GGTACGCAGTCCTTTCGAGTACCCACGCGGTTCTATCTAGTTACGCGTTAAACCA ACTAGAA (SEQ ID NO: 764), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT115 / 235B1195.70202WO00#14468377 v2TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGT GTGGTACGCAGTCCTTTCGAGTACCCACGCGGTTCTATCTAGTTACGCGTTAAAC CAACTAGAA (SEQ ID NO: 765), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG TGTGGTACGCAGTCCTTTCGAGTACCCACGCGGTTCTATCTAGTTACGCGTTAAA CCAACTAGAA (SEQ ID NO: 766), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGCAGTCCTTTCGAGTACCCACGCGGTTCTATCTAGTTACGCGTTAA ACCAACTAGAA (SEQ ID NO: 767), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGCAGTCCTTTCGAGTACCCACGCGGTTCTATCTAGTTACGCGTTA AACCAACTAGAA (SEQ ID NO: 768), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCAC GGGTGTGGTACGCAGTCCTTTCGAGTACCCACGCGGTTCTATCTAGTTACGCGTT AAACCAACTAGAA (SEQ ID NO: 769), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTGT GGTACGCAGTCCTTTCGAGTACCCACTTCAATATCGCGGTTCTATCTAGTTACGC GTTAAACCAACTAGAA (SEQ ID NO: 770), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGT GTGGTACGCAGTCCTTTCGAGTACCCACTCATAGAGCGCGGTTCTATCTAGTTAC GCGTTAAACCAACTAGAA (SEQ ID NO: 771), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG TGTGGTACGCAGTCCTTTCGAGTACCCACCTTTAAACCGCGGTTCTATCTAGTTAC GCGTTAAACCAACTAGAA (SEQ ID NO: 772), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG116 / 235B1195.70202WO00#14468377 v2GTGTGGTACGCAGTCCTTTCGAGTACCCACTCTTTAAACGCGGTTCTATCTAGTTA CGCGTTAAACCAACTAGAA (SEQ ID NO: 773), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGCAGTCCTTTCGAGTACCCACTAAAGAATCGCGGTTCTATCTAGT TACGCGTTAAACCAACTAGAA (SEQ ID NO: 774), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCAC GGGTGTGGTACGCAGTCCTTTCGAGTACCCACTCTTAAATCGCGGTTCTATCTAG TTACGCGTTAAACCAACTAGAA (SEQ ID NO: 775), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTGT GGTACGCAGTCCTTTCGAGTACCCACCGCGGTTCTATCTAGTTACGCGTTAAACC AACTAGAA (SEQ ID NO: 776), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGT GTGGTACGCAGTCCTTTCGAGTACCCACCGCGGTTCTATCTAGTTACGCGTTAAA CCAACTAGAA (SEQ ID NO: 777), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG TGTGGTACGCAGTCCTTTCGAGTACCCACCGCGGTTCTATCTAGTTACGCGTTAA ACCAACTAGAA (SEQ ID NO: 778), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGCAGTCCTTTCGAGTACCCACCGCGGTTCTATCTAGTTACGCGTTA AACCAACTAGAA (SEQ ID NO: 779), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGCAGTCCTTTCGAGTACCCACCGCGGTTCTATCTAGTTACGCGTT AAACCAACTAGAA (SEQ ID NO: 780), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCAC GGGTGTGGTACGCAGTCCTTTCGAGTACCCACCGCGGTTCTATCTAGTTACGCGT117 / 235B1195.70202WO00#14468377 v2TAAACCAACTAGAA (SEQ ID NO: 781), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT GTGGTACGCAGCCCCTTCGAGTACCCTGATAATACGCGGTTCTATCTAGTTACGC GTTAAACCAACTAGAA (SEQ ID NO: 782), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT GTGGTACGCAGTCCCTTCGAGTACCCTGATAATACGCGGTTCTATCTAGTTACGC GTTAAACCAACTAGAA (SEQ ID NO: 783), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT GTGGTACGCTCTCCCTTCGAGTACCCTGATAATACGCGGTTCTATCTAGTTACGC GTTAAACCAACTAGAA (SEQ ID NO: 784), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT GTGGTACGCTCCCCCTTCGAGTACCCTGATAATACGCGGTTCTATCTAGTTACGC GTTAAACCAACTAGAA (SEQ ID NO: 785), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT GTGGTACGCTCACCCTTCGAGTACCCTCCTCTTACGCGGTTCTATCTAGTTACGCG TTAAACCAACTAGAA (SEQ ID NO: 786), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT GTGGTACGCTCGCCCTTCGAGTACCCTGATAATACGCGGTTCTATCTAGTTACGC GTTAAACCAACTAGAA (SEQ ID NO: 787), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT GTGGTACGGAGCCCCTTCGAGTACCCTTTAATAACGCGGTTCTATCTAGTTACGC GTTAAACCAACTAGAA (SEQ ID NO: 788), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT GTGGTACGGAGTCCCTTCGAGTACCCTTCTCAAACGCGGTTCTATCTAGTTACGC GTTAAACCAACTAGAA (SEQ ID NO: 789),118 / 235B1195.70202WO00#14468377 v2GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT GTGGTACGGTCTCCCTTCGAGTACCCTAAATTTACGCGGTTCTATCTAGTTACGCG TTAAACCAACTAGAA (SEQ ID NO: 790), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT GTGGTACGGTCCCCCTTCGAGTACCCTGATAATACGCGGTTCTATCTAGTTACGC GTTAAACCAACTAGAA (SEQ ID NO: 791), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT GTGGTACGGTCACCCTTCGAGTACCCTGATAATACGCGGTTCTATCTAGTTACGC GTTAAACCAACTAGAA (SEQ ID NO: 792), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT GTGGTACGGTCGCCCTTCGAGTACCCTGATAATACGCGGTTCTATCTAGTTACGC GTTAAACCAACTAGAA (SEQ ID NO: 793), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT GTGGTACGCAGCCCGTTCGAGTACCCTGATAATACGCGGTTCTATCTAGTTACGC GTTAAACCAACTAGAA (SEQ ID NO: 794), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT GTGGTACGCAGTCCGTTCGAGTACCCTTCTTCACCGCGGTTCTATCTAGTTACGCG TTAAACCAACTAGAA (SEQ ID NO: 795), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT GTGGTACGCTCTCCGTTCGAGTACCCTGATAATACGCGGTTCTATCTAGTTACGC GTTAAACCAACTAGAA (SEQ ID NO: 796), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT GTGGTACGCTCCCCGTTCGAGTACCCTGATAATACGCGGTTCTATCTAGTTACGC GTTAAACCAACTAGAA (SEQ ID NO: 797), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT119 / 235B1195.70202WO00#14468377 v2TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT GTGGTACGCTCACCGTTCGAGTACCCAATTTAATCGCGGTTCTATCTAGTTACGC GTTAAACCAACTAGAA (SEQ ID NO: 798), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT GTGGTACGCTCGCCGTTCGAGTACCCTGATAATACGCGGTTCTATCTAGTTACGC GTTAAACCAACTAGAA (SEQ ID NO: 799), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT GTGGTACGGAGCCCGTTCGAGTACCCTGAAATTACGCGGTTCTATCTAGTTACGC GTTAAACCAACTAGAA (SEQ ID NO: 800), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT GTGGTACGGAGTCCGTTCGAGTACCCTAAATTGACGCGGTTCTATCTAGTTACGC GTTAAACCAACTAGAA (SEQ ID NO: 801), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT GTGGTACGGTCTCCGTTCGAGTACCCTAAATTAACGCGGTTCTATCTAGTTACGC GTTAAACCAACTAGAA (SEQ ID NO: 802), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT GTGGTACGGTCCCCGTTCGAGTACCCTTAAATGACGCGGTTCTATCTAGTTACGC GTTAAACCAACTAGAA (SEQ ID NO: 803), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT GTGGTACGGTCACCGTTCGAGTACCCTGAAATAACGCGGTTCTATCTAGTTACGC GTTAAACCAACTAGAA (SEQ ID NO: 804), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT GTGGTACGGTCGCCGTTCGAGTACCCTAATTGAACGCGGTTCTATCTAGTTACGC GTTAAACCAACTAGAA (SEQ ID NO: 805), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT120 / 235B1195.70202WO00#14468377 v2GTGGTACGCAGCCCATTCGAGTACCCTGATAATACGCGGTTCTATCTAGTTACGC GTTAAACCAACTAGAA (SEQ ID NO: 806), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT GTGGTACGCAGTCCATTCGAGTACCCTGAATAACCGCGGTTCTATCTAGTTACGC GTTAAACCAACTAGAA (SEQ ID NO: 807), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT GTGGTACGCTCTCCATTCGAGTACCCTGATAAACCGCGGTTCTATCTAGTTACGC GTTAAACCAACTAGAA (SEQ ID NO: 808), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT GTGGTACGCTCCCCATTCGAGTACCCTGATAATACGCGGTTCTATCTAGTTACGC GTTAAACCAACTAGAA (SEQ ID NO: 809), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT GTGGTACGCTCACCATTCGAGTACCCTTCCTAACCGCGGTTCTATCTAGTTACGC GTTAAACCAACTAGAA (SEQ ID NO: 810), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT GTGGTACGCTCGCCATTCGAGTACCCTGATAATACGCGGTTCTATCTAGTTACGC GTTAAACCAACTAGAA (SEQ ID NO: 811), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT GTGGTACGGAGCCCATTCGAGTACCCTTCTGAACCGCGGTTCTATCTAGTTACGC GTTAAACCAACTAGAA (SEQ ID NO: 812), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT GTGGTACGGAGTCCATTCGAGTACCCTGAATGAACGCGGTTCTATCTAGTTACGC GTTAAACCAACTAGAA (SEQ ID NO: 813), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT GTGGTACGGTCTCCATTCGAGTACCCTGATAATACGCGGTTCTATCTAGTTACGC121 / 235B1195.70202WO00#14468377 v2GTTAAACCAACTAGAA (SEQ ID NO: 814), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT GTGGTACGGTCCCCATTCGAGTACCCTGAAATGACGCGGTTCTATCTAGTTACGC GTTAAACCAACTAGAA (SEQ ID NO: 815), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT GTGGTACGGTCACCATTCGAGTACCCTGATAATACGCGGTTCTATCTAGTTACGC GTTAAACCAACTAGAA (SEQ ID NO: 816), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT GTGGTACGGTCGCCATTCGAGTACCCTGATAATACGCGGTTCTATCTAGTTACGC GTTAAACCAACTAGAA (SEQ ID NO: 817), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT GTGGTACGCAGCCCTTTCGAGTACCCTGATAATACGCGGTTCTATCTAGTTACGC GTTAAACCAACTAGAA (SEQ ID NO: 818), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT GTGGTACGCTCTCCTTTCGAGTACCCTGATAATACGCGGTTCTATCTAGTTACGCG TTAAACCAACTAGAA (SEQ ID NO: 819), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT GTGGTACGCTCCCCTTTCGAGTACCCTGATAATACGCGGTTCTATCTAGTTACGC GTTAAACCAACTAGAA (SEQ ID NO: 820), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT GTGGTACGCTCACCTTTCGAGTACCCTAATAATTCGCGGTTCTATCTAGTTACGCG TTAAACCAACTAGAA (SEQ ID NO: 821), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT GTGGTACGCTCGCCTTTCGAGTACCCTGATAATACGCGGTTCTATCTAGTTACGC GTTAAACCAACTAGAA (SEQ ID NO: 822),122 / 235B1195.70202WO00#14468377 v2GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT GTGGTACGGAGCCCTTTCGAGTACCCTTCTTCAACGCGGTTCTATCTAGTTACGC GTTAAACCAACTAGAA (SEQ ID NO: 823), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT GTGGTACGGAGTCCTTTCGAGTACCCTGATAATACGCGGTTCTATCTAGTTACGC GTTAAACCAACTAGAA (SEQ ID NO: 824), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT GTGGTACGGTCTCCTTTCGAGTACCCTGTTAAACCGCGGTTCTATCTAGTTACGCG TTAAACCAACTAGAA (SEQ ID NO: 825), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT GTGGTACGGTCCCCTTTCGAGTACCCTGATAATACGCGGTTCTATCTAGTTACGC GTTAAACCAACTAGAA (SEQ ID NO: 826), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT GTGGTACGGTCACCTTTCGAGTACCCTGATAATACGCGGTTCTATCTAGTTACGC GTTAAACCAACTAGAA (SEQ ID NO: 827), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT GTGGTACGGTCGCCTTTCGAGTACCCTGATAATACGCGGTTCTATCTAGTTACGC GTTAAACCAACTAGAA (SEQ ID NO: 828), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGCAGCCCCTTCGAGTACCCAATTAAATCGCGGTTCTATCTAGTTA CGCGTTAAACCAACTAGAA (SEQ ID NO: 829), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGCAGTCCCTTCGAGTACCCTCCTCTTCCGCGGTTCTATCTAGTTAC GCGTTAAACCAACTAGAA (SEQ ID NO: 830), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT123 / 235B1195.70202WO00#14468377 v2TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGCTCTCCCTTCGAGTACCCTTTAATAACGCGGTTCTATCTAGTTAC GCGTTAAACCAACTAGAA (SEQ ID NO: 831), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGCTCCCCCTTCGAGTACCCTAATAATGCGCGGTTCTATCTAGTTA CGCGTTAAACCAACTAGAA (SEQ ID NO: 832), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGCTCACCCTTCGAGTACCCTAATAAACCGCGGTTCTATCTAGTTA CGCGTTAAACCAACTAGAA (SEQ ID NO: 833), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGCTCGCCCTTCGAGTACCCTCCTAATACGCGGTTCTATCTAGTTAC GCGTTAAACCAACTAGAA (SEQ ID NO: 834), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGGAGCCCCTTCGAGTACCCTGATAATACGCGGTTCTATCTAGTTA CGCGTTAAACCAACTAGAA (SEQ ID NO: 835), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGGAGTCCCTTCGAGTACCCTAAATGAGCGCGGTTCTATCTAGTTA CGCGTTAAACCAACTAGAA (SEQ ID NO: 836), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGGTCTCCCTTCGAGTACCCTGATAATACGCGGTTCTATCTAGTTA CGCGTTAAACCAACTAGAA (SEQ ID NO: 837), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGGTCCCCCTTCGAGTACCCTGAATTAACGCGGTTCTATCTAGTTA CGCGTTAAACCAACTAGAA (SEQ ID NO: 838), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG124 / 235B1195.70202WO00#14468377 v2GGTGTGGTACGGTCACCCTTCGAGTACCCTTCCATTACGCGGTTCTATCTAGTTAC GCGTTAAACCAACTAGAA (SEQ ID NO: 839), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGGTCGCCCTTCGAGTACCCTCCTCATTCGCGGTTCTATCTAGTTAC GCGTTAAACCAACTAGAA (SEQ ID NO: 840), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGCAGCCCGTTCGAGTACCCTAATAAATCGCGGTTCTATCTAGTTA CGCGTTAAACCAACTAGAA (SEQ ID NO: 841), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGCAGTCCGTTCGAGTACCCTATTTAAACGCGGTTCTATCTAGTTA CGCGTTAAACCAACTAGAA (SEQ ID NO: 842), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGCTCTCCGTTCGAGTACCCTAAATTTACGCGGTTCTATCTAGTTAC GCGTTAAACCAACTAGAA (SEQ ID NO: 843), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGCTCCCCGTTCGAGTACCCTAATAATGCGCGGTTCTATCTAGTTA CGCGTTAAACCAACTAGAA (SEQ ID NO: 844), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGCTCACCGTTCGAGTACCCTATTAAATCGCGGTTCTATCTAGTTA CGCGTTAAACCAACTAGAA (SEQ ID NO: 845), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGCTCGCCGTTCGAGTACCCTAATTAAGCGCGGTTCTATCTAGTTA CGCGTTAAACCAACTAGAA (SEQ ID NO: 846), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGGAGCCCGTTCGAGTACCCTTAATGAACGCGGTTCTATCTAGTTA125 / 235B1195.70202WO00#14468377 v2CGCGTTAAACCAACTAGAA (SEQ ID NO: 847), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGGAGTCCGTTCGAGTACCCTTAATGAACGCGGTTCTATCTAGTTA CGCGTTAAACCAACTAGAA (SEQ ID NO: 848), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGGTCTCCGTTCGAGTACCCTGATGAACCGCGGTTCTATCTAGTTA CGCGTTAAACCAACTAGAA (SEQ ID NO: 849), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGGTCCCCGTTCGAGTACCCTATTTAACCGCGGTTCTATCTAGTTAC GCGTTAAACCAACTAGAA (SEQ ID NO: 850), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGGTCACCGTTCGAGTACCCTATTCAATCGCGGTTCTATCTAGTTA CGCGTTAAACCAACTAGAA (SEQ ID NO: 851), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGGTCGCCGTTCGAGTACCCTTCGAAACCGCGGTTCTATCTAGTTA CGCGTTAAACCAACTAGAA (SEQ ID NO: 852), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGCAGCCCATTCGAGTACCCTTCCTAAACGCGGTTCTATCTAGTTA CGCGTTAAACCAACTAGAA (SEQ ID NO: 853), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGCAGTCCATTCGAGTACCCTAAATAAACGCGGTTCTATCTAGTTA CGCGTTAAACCAACTAGAA (SEQ ID NO: 854), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGCTCTCCATTCGAGTACCCTAATGAAACGCGGTTCTATCTAGTTA CGCGTTAAACCAACTAGAA (SEQ ID NO: 855),126 / 235B1195.70202WO00#14468377 v2GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGCTCCCCATTCGAGTACCCTAATAAACCGCGGTTCTATCTAGTTA CGCGTTAAACCAACTAGAA (SEQ ID NO: 856), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGCTCACCATTCGAGTACCCTATTAAATCGCGGTTCTATCTAGTTA CGCGTTAAACCAACTAGAA (SEQ ID NO: 857), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGCTCGCCATTCGAGTACCCTTTCTAAACGCGGTTCTATCTAGTTAC GCGTTAAACCAACTAGAA (SEQ ID NO: 858), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGGAGCCCATTCGAGTACCCTGATAATACGCGGTTCTATCTAGTTA CGCGTTAAACCAACTAGAA (SEQ ID NO: 859), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGGAGTCCATTCGAGTACCCTTGATAACCGCGGTTCTATCTAGTTA CGCGTTAAACCAACTAGAA (SEQ ID NO: 860), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGGTCTCCATTCGAGTACCCTTCTTAACCGCGGTTCTATCTAGTTAC GCGTTAAACCAACTAGAA (SEQ ID NO: 861), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGGTCCCCATTCGAGTACCCTCCTTAATCGCGGTTCTATCTAGTTAC GCGTTAAACCAACTAGAA (SEQ ID NO: 862), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGGTCACCATTCGAGTACCCTCCTCAAACGCGGTTCTATCTAGTTA CGCGTTAAACCAACTAGAA (SEQ ID NO: 863), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT127 / 235B1195.70202WO00#14468377 v2TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGGTCGCCATTCGAGTACCCTCTTAAATCGCGGTTCTATCTAGTTA CGCGTTAAACCAACTAGAA (SEQ ID NO: 864), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGCAGCCCTTTCGAGTACCCAATAAATGCGCGGTTCTATCTAGTTA CGCGTTAAACCAACTAGAA (SEQ ID NO: 865), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGCTCTCCTTTCGAGTACCCGTTTAAACCGCGGTTCTATCTAGTTAC GCGTTAAACCAACTAGAA (SEQ ID NO: 866), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGCTCCCCTTTCGAGTACCCTCCTTCACCGCGGTTCTATCTAGTTAC GCGTTAAACCAACTAGAA (SEQ ID NO: 867), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGCTCACCTTTCGAGTACCCTCCTGAACCGCGGTTCTATCTAGTTAC GCGTTAAACCAACTAGAA (SEQ ID NO: 868), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGCTCGCCTTTCGAGTACCCTAAATAAACGCGGTTCTATCTAGTTA CGCGTTAAACCAACTAGAA (SEQ ID NO: 869), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGGAGCCCTTTCGAGTACCCTGATAATACGCGGTTCTATCTAGTTA CGCGTTAAACCAACTAGAA (SEQ ID NO: 870), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGGAGTCCTTTCGAGTACCCTGATTAACCGCGGTTCTATCTAGTTA CGCGTTAAACCAACTAGAA (SEQ ID NO: 871), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT128 / 235B1195.70202WO00#14468377 v2TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGGTCTCCTTTCGAGTACCCTTCTAAAGCGCGGTTCTATCTAGTTAC GCGTTAAACCAACTAGAA (SEQ ID NO: 872), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGGTCCCCTTTCGAGTACCCTGATAATACGCGGTTCTATCTAGTTA CGCGTTAAACCAACTAGAA (SEQ ID NO: 873), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGGTCACCTTTCGAGTACCCTGATAATACGCGGTTCTATCTAGTTA CGCGTTAAACCAACTAGAA (SEQ ID NO: 874), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGGTCGCCTTTCGAGTACCCTGATAATACGCGGTTCTATCTAGTTA CGCGTTAAACCAACTAGAA (SEQ ID NO: 875), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGCAGCCCCTTCGAGTACCAATCTCTTCGCGGTTCTATCTAGTTACGC GTTAAACCAACTAGAA (SEQ ID NO: 876), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGCAGTCCCTTCGAGTACCAATTTAAGCGCGGTTCTATCTAGTTACG CGTTAAACCAACTAGAA (SEQ ID NO: 877), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGCTCTCCCTTCGAGTACCAGAAATAACGCGGTTCTATCTAGTTACG CGTTAAACCAACTAGAA (SEQ ID NO: 878), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGCTCCCCCTTCGAGTACCAAATGAATCGCGGTTCTATCTAGTTACG CGTTAAACCAACTAGAA (SEQ ID NO: 879), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG129 / 235B1195.70202WO00#14468377 v2GTGTGGTACGCTCACCCTTCGAGTACCATCCTGACCGCGGTTCTATCTAGTTACG CGTTAAACCAACTAGAA (SEQ ID NO: 880), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGCTCGCCCTTCGAGTACCATTCTAAACGCGGTTCTATCTAGTTACG CGTTAAACCAACTAGAA (SEQ ID NO: 881), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGGAGCCCCTTCGAGTACCAAATTAACCGCGGTTCTATCTAGTTACG CGTTAAACCAACTAGAA (SEQ ID NO: 882), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGGAGTCCCTTCGAGTACCGTCTAAATCGCGGTTCTATCTAGTTACG CGTTAAACCAACTAGAA (SEQ ID NO: 883), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGGTCTCCCTTCGAGTACCAAATTCTCCGCGGTTCTATCTAGTTACGC GTTAAACCAACTAGAA (SEQ ID NO: 884), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGGTCCCCCTTCGAGTACCAATTAATTCGCGGTTCTATCTAGTTACGC GTTAAACCAACTAGAA (SEQ ID NO: 885), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGGTCACCCTTCGAGTACCAAATTTATCGCGGTTCTATCTAGTTACG CGTTAAACCAACTAGAA (SEQ ID NO: 886), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGGTCGCCCTTCGAGTACCATTAAATTCGCGGTTCTATCTAGTTACG CGTTAAACCAACTAGAA (SEQ ID NO: 887), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGCAGCCCGTTCGAGTACCATTCCTTACGCGGTTCTATCTAGTTACG130 / 235B1195.70202WO00#14468377 v2CGTTAAACCAACTAGAA (SEQ ID NO: 888), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGCAGTCCGTTCGAGTACCAAATCTTGCGCGGTTCTATCTAGTTACG CGTTAAACCAACTAGAA (SEQ ID NO: 889), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGCTCTCCGTTCGAGTACCAATCTTCACGCGGTTCTATCTAGTTACGC GTTAAACCAACTAGAA (SEQ ID NO: 890), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGCTCCCCGTTCGAGTACCAATTTAAACGCGGTTCTATCTAGTTACG CGTTAAACCAACTAGAA (SEQ ID NO: 891), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGCTCACCGTTCGAGTACCAATCTAAACGCGGTTCTATCTAGTTACG CGTTAAACCAACTAGAA (SEQ ID NO: 892), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGCTCGCCGTTCGAGTACCGTCTAATACGCGGTTCTATCTAGTTACG CGTTAAACCAACTAGAA (SEQ ID NO: 893), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGGAGCCCGTTCGAGTACCGTGAAATACGCGGTTCTATCTAGTTACG CGTTAAACCAACTAGAA (SEQ ID NO: 894), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGGAGTCCGTTCGAGTACCGTTGAAACCGCGGTTCTATCTAGTTACG CGTTAAACCAACTAGAA (SEQ ID NO: 895), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGGTCTCCGTTCGAGTACCATTTAATACGCGGTTCTATCTAGTTACGC GTTAAACCAACTAGAA (SEQ ID NO: 896),131 / 235B1195.70202WO00#14468377 v2GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGGTCCCCGTTCGAGTACCAGAAATTCCGCGGTTCTATCTAGTTACG CGTTAAACCAACTAGAA (SEQ ID NO: 897), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGGTCACCGTTCGAGTACCAATCTCTCCGCGGTTCTATCTAGTTACG CGTTAAACCAACTAGAA (SEQ ID NO: 898), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGGTCGCCGTTCGAGTACCGTAAATTACGCGGTTCTATCTAGTTACG CGTTAAACCAACTAGAA (SEQ ID NO: 899), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGCAGCCCATTCGAGTACCATCCTTAACGCGGTTCTATCTAGTTACG CGTTAAACCAACTAGAA (SEQ ID NO: 900), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGCAGTCCATTCGAGTACCAAATGAAACGCGGTTCTATCTAGTTACG CGTTAAACCAACTAGAA (SEQ ID NO: 901), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGCTCTCCATTCGAGTACCAATTTCTCCGCGGTTCTATCTAGTTACGC GTTAAACCAACTAGAA (SEQ ID NO: 902), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGCTCCCCATTCGAGTACCAATTAAATCGCGGTTCTATCTAGTTACG CGTTAAACCAACTAGAA (SEQ ID NO: 903), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGCTCACCATTCGAGTACCAATTAAAGCGCGGTTCTATCTAGTTACG CGTTAAACCAACTAGAA (SEQ ID NO: 904), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT132 / 235B1195.70202WO00#14468377 v2TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGCTCGCCATTCGAGTACCAAATTAAACGCGGTTCTATCTAGTTACG CGTTAAACCAACTAGAA (SEQ ID NO: 905), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGGAGCCCATTCGAGTACCATTTAAAGCGCGGTTCTATCTAGTTACG CGTTAAACCAACTAGAA (SEQ ID NO: 906), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGGAGTCCATTCGAGTACCAAATTTAACGCGGTTCTATCTAGTTACG CGTTAAACCAACTAGAA (SEQ ID NO: 907), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGGTCTCCATTCGAGTACCAAATCTTACGCGGTTCTATCTAGTTACG CGTTAAACCAACTAGAA (SEQ ID NO: 908), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGGTCCCCATTCGAGTACCAATTAATGCGCGGTTCTATCTAGTTACG CGTTAAACCAACTAGAA (SEQ ID NO: 909), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGGTCACCATTCGAGTACCAGAAATTACGCGGTTCTATCTAGTTACG CGTTAAACCAACTAGAA (SEQ ID NO: 910), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGGTCGCCATTCGAGTACCAATCTAAGCGCGGTTCTATCTAGTTACG CGTTAAACCAACTAGAA (SEQ ID NO: 911), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGCAGCCCTTTCGAGTACCAATCTAAGCGCGGTTCTATCTAGTTACG CGTTAAACCAACTAGAA (SEQ ID NO: 912), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG133 / 235B1195.70202WO00#14468377 v2GTGTGGTACGCTCTCCTTTCGAGTACCAAATTCTACGCGGTTCTATCTAGTTACGC GTTAAACCAACTAGAA (SEQ ID NO: 913), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGCTCCCCTTTCGAGTACCATTTAAAGCGCGGTTCTATCTAGTTACGC GTTAAACCAACTAGAA (SEQ ID NO: 914), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGCTCACCTTTCGAGTACCATTCTAAGCGCGGTTCTATCTAGTTACGC GTTAAACCAACTAGAA (SEQ ID NO: 915), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGCTCGCCTTTCGAGTACCAATCTTCACGCGGTTCTATCTAGTTACGC GTTAAACCAACTAGAA (SEQ ID NO: 916), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGGAGCCCTTTCGAGTACCAAATTAACCGCGGTTCTATCTAGTTACG CGTTAAACCAACTAGAA (SEQ ID NO: 917), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGGAGTCCTTTCGAGTACCAATCTCTTCGCGGTTCTATCTAGTTACGC GTTAAACCAACTAGAA (SEQ ID NO: 918), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGGTCTCCTTTCGAGTACCAATTAAATCGCGGTTCTATCTAGTTACGC GTTAAACCAACTAGAA (SEQ ID NO: 919), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGGTCCCCTTTCGAGTACCATTAAATACGCGGTTCTATCTAGTTACG CGTTAAACCAACTAGAA (SEQ ID NO: 920), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGGTCACCTTTCGAGTACCAAATCTTCCGCGGTTCTATCTAGTTACGC134 / 235B1195.70202WO00#14468377 v2GTTAAACCAACTAGAA (SEQ ID NO: 921), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGGTCGCCTTTCGAGTACCAATTAATACGCGGTTCTATCTAGTTACG CGTTAAACCAACTAGAA (SEQ ID NO: 922), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGCAGCCCCTTCGAGTACCAATTAAATCGCGGTTCTATCTAGTTAC GCGTTAAACCAACTAGAA (SEQ ID NO: 923), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGCAGTCCCTTCGAGTACCAATCTTAACGCGGTTCTATCTAGTTAC GCGTTAAACCAACTAGAA (SEQ ID NO: 924), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGCTCTCCCTTCGAGTACCAAATTCGTCGCGGTTCTATCTAGTTACG CGTTAAACCAACTAGAA (SEQ ID NO: 925), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGCTCCCCCTTCGAGTACCAATCTAAGCGCGGTTCTATCTAGTTAC GCGTTAAACCAACTAGAA (SEQ ID NO: 926), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGCTCACCCTTCGAGTACCATCCTTTACGCGGTTCTATCTAGTTACG CGTTAAACCAACTAGAA (SEQ ID NO: 927), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGCTCGCCCTTCGAGTACCATTAATTACGCGGTTCTATCTAGTTAC GCGTTAAACCAACTAGAA (SEQ ID NO: 928), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGGAGCCCCTTCGAGTACCGTCTAAACCGCGGTTCTATCTAGTTAC GCGTTAAACCAACTAGAA (SEQ ID NO: 929),135 / 235B1195.70202WO00#14468377 v2GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGGAGTCCCTTCGAGTACCAGAAATTACGCGGTTCTATCTAGTTAC GCGTTAAACCAACTAGAA (SEQ ID NO: 930), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGGTCTCCCTTCGAGTACCAAATCTTCCGCGGTTCTATCTAGTTACG CGTTAAACCAACTAGAA (SEQ ID NO: 931), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGGTCCCCCTTCGAGTACCAATTAATACGCGGTTCTATCTAGTTAC GCGTTAAACCAACTAGAA (SEQ ID NO: 932), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGGTCACCCTTCGAGTACCAATCTGATCGCGGTTCTATCTAGTTAC GCGTTAAACCAACTAGAA (SEQ ID NO: 933), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGGTCGCCCTTCGAGTACCAAATTCTACGCGGTTCTATCTAGTTAC GCGTTAAACCAACTAGAA (SEQ ID NO: 934), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGCAGCCCGTTCGAGTACCATCCTGACCGCGGTTCTATCTAGTTAC GCGTTAAACCAACTAGAA (SEQ ID NO: 935), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGCAGTCCGTTCGAGTACCAAATCTCACGCGGTTCTATCTAGTTAC GCGTTAAACCAACTAGAA (SEQ ID NO: 936), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGCTCTCCGTTCGAGTACCATTCTAAACGCGGTTCTATCTAGTTAC GCGTTAAACCAACTAGAA (SEQ ID NO: 937), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT136 / 235B1195.70202WO00#14468377 v2TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGCTCCCCGTTCGAGTACCAATTAAATCGCGGTTCTATCTAGTTAC GCGTTAAACCAACTAGAA (SEQ ID NO: 938), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGCTCACCGTTCGAGTACCATTAATGACGCGGTTCTATCTAGTTAC GCGTTAAACCAACTAGAA (SEQ ID NO: 939), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGCTCGCCGTTCGAGTACCATTTAAATCGCGGTTCTATCTAGTTAC GCGTTAAACCAACTAGAA (SEQ ID NO: 940), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGGAGCCCGTTCGAGTACCATCTAATGCGCGGTTCTATCTAGTTAC GCGTTAAACCAACTAGAA (SEQ ID NO: 941), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGGAGTCCGTTCGAGTACCATTCTTAACGCGGTTCTATCTAGTTAC GCGTTAAACCAACTAGAA (SEQ ID NO: 942), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGGTCTCCGTTCGAGTACCAAATCTTTCGCGGTTCTATCTAGTTACG CGTTAAACCAACTAGAA (SEQ ID NO: 943), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGGTCCCCGTTCGAGTACCAATTAATTCGCGGTTCTATCTAGTTAC GCGTTAAACCAACTAGAA (SEQ ID NO: 944), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGGTCACCGTTCGAGTACCGTAAATGACGCGGTTCTATCTAGTTAC GCGTTAAACCAACTAGAA (SEQ ID NO: 945), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG137 / 235B1195.70202WO00#14468377 v2GGTGTGGTACGGTCGCCGTTCGAGTACCAAATTCGACGCGGTTCTATCTAGTTAC GCGTTAAACCAACTAGAAGGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCT GGAAACAGCATAGCAAGTTTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGT GGCACCGAGTCGGTGCCGGGTGTGGTACGCAGCCCATTCGAGTACCATTAAATA CGCGGTTCTATCTAGTTACGCGTTAAACCAACTAGAA (SEQ ID NO: 946), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGCAGTCCATTCGAGTACCAAATTAAGCGCGGTTCTATCTAGTTAC GCGTTAAACCAACTAGAA (SEQ ID NO: 947), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGCTCTCCATTCGAGTACCGTTAAATACGCGGTTCTATCTAGTTAC GCGTTAAACCAACTAGAA (SEQ ID NO: 948), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGCTCCCCATTCGAGTACCAGATGAAACGCGGTTCTATCTAGTTAC GCGTTAAACCAACTAGAA (SEQ ID NO: 949), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGCTCACCATTCGAGTACCGTTAATAACGCGGTTCTATCTAGTTAC GCGTTAAACCAACTAGAA (SEQ ID NO: 950), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGCTCGCCATTCGAGTACCAGAAATTTCGCGGTTCTATCTAGTTAC GCGTTAAACCAACTAGAA (SEQ ID NO: 951), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGGAGCCCATTCGAGTACCAGAAATGACGCGGTTCTATCTAGTTAC GCGTTAAACCAACTAGAA (SEQ ID NO: 952), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGGAGTCCATTCGAGTACCAATTTAAACGCGGTTCTATCTAGTTAC GCGTTAAACCAACTAGAA (SEQ ID NO: 953),138 / 235B1195.70202WO00#14468377 v2GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGGTCTCCATTCGAGTACCAATTTAAACGCGGTTCTATCTAGTTAC GCGTTAAACCAACTAGAA (SEQ ID NO: 954), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGGTCCCCATTCGAGTACCGTGATAAACGCGGTTCTATCTAGTTAC GCGTTAAACCAACTAGAA (SEQ ID NO: 955), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGGTCACCATTCGAGTACCAAATTAATCGCGGTTCTATCTAGTTAC GCGTTAAACCAACTAGAA (SEQ ID NO: 956), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGGTCGCCATTCGAGTACCGTCTTAACCGCGGTTCTATCTAGTTAC GCGTTAAACCAACTAGAA (SEQ ID NO: 957), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGCAGCCCTTTCGAGTACCAATTAATCCGCGGTTCTATCTAGTTAC GCGTTAAACCAACTAGAA (SEQ ID NO: 958), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGCTCTCCTTTCGAGTACCAATTAATTCGCGGTTCTATCTAGTTACG CGTTAAACCAACTAGAA (SEQ ID NO: 959), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGCTCCCCTTTCGAGTACCGTTCTAACCGCGGTTCTATCTAGTTACG CGTTAAACCAACTAGAA (SEQ ID NO: 960), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGCTCACCTTTCGAGTACCAAATTCTGCGCGGTTCTATCTAGTTAC GCGTTAAACCAACTAGAA (SEQ ID NO: 961), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT139 / 235B1195.70202WO00#14468377 v2TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGCTCGCCTTTCGAGTACCAATTAATTCGCGGTTCTATCTAGTTACG CGTTAAACCAACTAGAA (SEQ ID NO: 962), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGGAGCCCTTTCGAGTACCAATTTAAGCGCGGTTCTATCTAGTTAC GCGTTAAACCAACTAGAA (SEQ ID NO: 963), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGGAGTCCTTTCGAGTACCAAATTGAACGCGGTTCTATCTAGTTAC GCGTTAAACCAACTAGAA (SEQ ID NO: 964), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGGTCTCCTTTCGAGTACCAGAAATAACGCGGTTCTATCTAGTTAC GCGTTAAACCAACTAGAA (SEQ ID NO: 965), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGGTCCCCTTTCGAGTACCAAATCTAACGCGGTTCTATCTAGTTAC GCGTTAAACCAACTAGAA (SEQ ID NO: 966), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGGTCACCTTTCGAGTACCAATTCTTACGCGGTTCTATCTAGTTACG CGTTAAACCAACTAGAA (SEQ ID NO: 967), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCCG GGTGTGGTACGGTCGCCTTTCGAGTACCGTTAAACACGCGGTTCTATCTAGTTAC GCGTTAAACCAACTAGAA (SEQ ID NO: 968), AGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGCAGCCCCTTCGAGTACCCGCGGTTCTATCTAGTTACGCGTTAAAC CAACTAGAA (SEQ ID NO: 969), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG140 / 235B1195.70202WO00#14468377 v2GTGTGGTACGCAGCCCCTTCGAGTACCCGCGGTTCTATCTAGTTACGCGTTAAAC CAACTAGAA (SEQ ID NO: 970), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGCAGCCCGTTCGAGTACCCGCGGTTCTATCTAGTTACGCGTTAAAC CAACTAGAA (SEQ ID NO: 971), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGCAGTCCGTTCGAGTACCCGCGGTTCTATCTAGTTACGCGTTAAAC CAACTAGAA (SEQ ID NO: 972), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGCTCTCCGTTCGAGTACCCGCGGTTCTATCTAGTTACGCGTTAAAC CAACTAGAA (SEQ ID NO: 973), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGCTCCCCGTTCGAGTACCCGCGGTTCTATCTAGTTACGCGTTAAAC CAACTAGAA (SEQ ID NO: 974), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGCTCACCGTTCGAGTACCCGCGGTTCTATCTAGTTACGCGTTAAAC CAACTAGAA (SEQ ID NO: 975), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGCTCGCCGTTCGAGTACCCGCGGTTCTATCTAGTTACGCGTTAAAC CAACTAGAA (SEQ ID NO: 976), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGGAGCCCGTTCGAGTACCCGCGGTTCTATCTAGTTACGCGTTAAAC CAACTAGAA (SEQ ID NO: 977), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGGAGTCCGTTCGAGTACCCGCGGTTCTATCTAGTTACGCGTTAAAC141 / 235B1195.70202WO00#14468377 v2CAACTAGAA (SEQ ID NO: 978), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGGTCTCCGTTCGAGTACCCGCGGTTCTATCTAGTTACGCGTTAAAC CAACTAGAA (SEQ ID NO: 979), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGGTCCCCGTTCGAGTACCCGCGGTTCTATCTAGTTACGCGTTAAAC CAACTAGAA (SEQ ID NO: 980), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGGTCACCGTTCGAGTACCCGCGGTTCTATCTAGTTACGCGTTAAAC CAACTAGAA (SEQ ID NO: 981), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGGTCGCCGTTCGAGTACCCGCGGTTCTATCTAGTTACGCGTTAAAC CAACTAGAA (SEQ ID NO: 982), GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT ACGCAGTCCATTCGAGTACCCACAGTCGCGGTTCTATCTAGTTACGCGTTAAACC AACTAGAA (SEQ ID NO: 983), GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT ACGCAGTCCATTCGAGTACCCACAGCGCGGTTCTATCTAGTTACGCGTTAAACCA ACTAGAA (SEQ ID NO: 984), GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT ACGCAGTCCATTCGAGTACCCACACGCGGTTCTATCTAGTTACGCGTTAAACCAA CTAGAA (SEQ ID NO: 985), GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGG TGTGGTACGGTCGCCATTCGAGTACCCACAGTCGCGGTTCTATCTAGTTACGCGT TAAACCAACTAGAA (SEQ ID NO: 986),142 / 235B1195.70202WO00#14468377 v2GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGG TGTGGTACGGTCGCCATTCGAGTACCCACAGCGCGGTTCTATCTAGTTACGCGTT AAACCAACTAGAA (SEQ ID NO: 987), GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGG TGTGGTACGGTCGCCATTCGAGTACCCACACGCGGTTCTATCTAGTTACGCGTTA AACCAACTAGAA (SEQ ID NO: 988), GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGG TGTGGTACGTTCGCCATTCGAGTACCCACAGTCGCGGTTCTATCTAGTTACGCGTT AAACCAACTAGAA (SEQ ID NO: 989), GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGAC GGGTGTGGTACGTTCGCCATTCGAGTACCCACAGTCGCGGTTCTATCTAGTTACG CGTTAAACCAACTAGAA (SEQ ID NO: 990), GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGG TGTGGTACGTTCGCCATTCGAGTACCCACAGCGCGGTTCTATCTAGTTACGCGTT AAACCAACTAGAA (SEQ ID NO: 991), GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGG TGTGGTACGGTCTCCATTCGAGTACCCACAGTCGCGGTTCTATCTAGTTACGCGTT AAACCAACTAGAA (SEQ ID NO: 992), GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGG TGTGGTACGGTCTCCATTCGAGTACCCACAGCGCGGTTCTATCTAGTTACGCGTT AAACCAACTAGAA (SEQ ID NO: 993), GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT ACGCAGTCCCTTCGAGTACCCACAGTCGCGGTTCTATCTAGTTACGCGTTAAACC AACTAGAA (SEQ ID NO: 994), GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT143 / 235B1195.70202WO00#14468377 v2GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGG TGTGGTACGGTCTCCATTCGAGTACCCACACGCGGTTCTATCTAGTTACGCGTTA AACCAACTAGAA (SEQ ID NO: 995), GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT ACGCAGTCCCTTCGAGTACCCACAGCGCGGTTCTATCTAGTTACGCGTTAAACCA ACTAGAA (SEQ ID NO: 996), GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT ACGCAGTCCCTTCGAGTACCCACACGCGGTTCTATCTAGTTACGCGTTAAACCAA CTAGAA (SEQ ID NO: 997), GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGAC GGGTGTGGTACGTTCTCCATTCGAGTACCCACAGTCGCGGTTCTATCTAGTTACG CGTTAAACCAACTAGAA (SEQ ID NO: 998), GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGAC GGGTGTGGTACGTTCTCCATTCGAGTACCCACAGCGCGGTTCTATCTAGTTACGC GTTAAACCAACTAGAA (SEQ ID NO: 999), GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGAC GGGTGTGGTACGTTCTCCATTCGAGTACCCACACGCGGTTCTATCTAGTTACGCG TTAAACCAACTAGAA (SEQ ID NO: 1000), GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGG TGTGGTACGTTCGCCTTTCGAGTACCCACAGTCGCGGTTCTATCTAGTTACGCGTT AAACCAACTAGAA (SEQ ID NO: 1001), GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT ACGCAGTCCGTTCGAGTACCCACAGTCGCGGTTCTATCTAGTTACGCGTTAAACC AACTAGAA (SEQ ID NO: 1002), GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGG144 / 235B1195.70202WO00#14468377 v2TGTGGTACGTTCGCCTTTCGAGTACCCACAGCGCGGTTCTATCTAGTTACGCGTTA AACCAACTAGAA (SEQ ID NO: 1003), GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT ACGCAGTCCGTTCGAGTACCCACAGCGCGGTTCTATCTAGTTACGCGTTAAACCA ACTAGAA (SEQ ID NO: 1004), GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGG TGTGGTACGTTCGCCTTTCGAGTACCCACACGCGGTTCTATCTAGTTACGCGTTAA ACCAACTAGAA (SEQ ID NO: 1005), GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT ACGCAGTCCGTTCGAGTACCCACACGCGGTTCTATCTAGTTACGCGTTAAACCAA CTAGAA (SEQ ID NO: 1006), GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGG TGTGGTACGATCGCCATTCGAGTACCCACAGTCGCGGTTCTATCTAGTTACGCGT TAAACCAACTAGAA (SEQ ID NO: 1007), GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGG TGTGGTACGCTCGCCTTTCGAGTACCCACAGTCGCGGTTCTATCTAGTTACGCGTT AAACCAACTAGAA (SEQ ID NO: 1008), GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGG TGTGGTACGATCGCCTTTCGAGTACCCACAGTCGCGGTTCTATCTAGTTACGCGTT AAACCAACTAGAA (SEQ ID NO: 1009), GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGCG ACGGGTGTGGTACGCTCGCCGTTCGAGTACCCACAGTCGCGGTTCTATCTAGTTA CGCGTTAAACCAACTAGAA (SEQ ID NO: 1010), GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGAC GGGTGTGGTACGATCTCCATTCGAGTACCCACAGTCGCGGTTCTATCTAGTTACG145 / 235B1195.70202WO00#14468377 v2CGTTAAACCAACTAGAA (SEQ ID NO: 1011), GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGG TGTGGTACGGTCGCCTTTCGAGTACCCACAGTCGCGGTTCTATCTAGTTACGCGTT AAACCAACTAGAA (SEQ ID NO: 1012), GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGCG ACGGGTGTGGTACGGTCGCCGTTCGAGTACCCACAGTCGCGGTTCTATCTAGTTA CGCGTTAAACCAACTAGAA (SEQ ID NO: 1013), GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGAC GGGTGTGGTACGTTCGCCGTTCGAGTACCCACAGTCGCGGTTCTATCTAGTTACG CGTTAAACCAACTAGAA (SEQ ID NO: 1014), GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGAC GGGTGTGGTACGATCGCCGTTCGAGTACCCACAGTCGCGGTTCTATCTAGTTACG CGTTAAACCAACTAGAA (SEQ ID NO: 1015), GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGG TGTGGTACGGTCACCATTCGAGTACCCACAGTCGCGGTTCTATCTAGTTACGCGT TAAACCAACTAGAA (SEQ ID NO: 1016), GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT ACGCAGTCCTTTCGAGTACCCACAGTCGCGGTTCTATCTAGTTACGCGTTAAACC AACTAGAA (SEQ ID NO: 1017), GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGG TGTGGTACGTTCACCATTCGAGTACCCACAGTCGCGGTTCTATCTAGTTACGCGTT AAACCAACTAGAA (SEQ ID NO: 1018), GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCAAT GCGACGGGTGTGGTGCGATCGCCATTCGAGTACCCACAGTCGCGGTTCTATCTAG TTACGCGTTAAACCAACTAGAA (SEQ ID NO: 1019),146 / 235B1195.70202WO00#14468377 v2GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGG TGTGGTACGGTCACCCTTCGAGTACCCACAGTCGCGGTTCTATCTAGTTACGCGT TAAACCAACTAGAA (SEQ ID NO: 1020), GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGG TGTGGTACGATCACCATTCGAGTACCCACAGTCGCGGTTCTATCTAGTTACGCGT TAAACCAACTAGAA (SEQ ID NO: 1021), GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGG TGTGGTACGCTCTCCATTCGAGTACCCACAGTCGCGGTTCTATCTAGTTACGCGTT AAACCAACTAGAA (SEQ ID NO: 1022), GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT GTGGTACGCTCACCATTCGAGTACCCACAGTCGCGGTTCTATCTAGTTACGCGTT AAACCAACTAGAA (SEQ ID NO: 1023), GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCAAT GCGACGGGTGTGGTACGATCACCCTTCGAGTACCCACAGTCGCGGTTCTATCTAG TTACGCGTTAAACCAACTAGAA (SEQ ID NO: 1024), GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCAAT GCGACGGGTGTGGTGCGCTCGCCGTTCGAGTACCCACAGTCGCGGTTCTATCTAG TTACGCGTTAAACCAACTAGAA (SEQ ID NO: 1025), GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCAAT GCGACGGGTGTGGTGCGCTCGCCATTCGAGTACCCACAGTCGCGGTTCTATCTAG TTACGCGTTAAACCAACTAGAA (SEQ ID NO: 1026), GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGT GTGGTACGCTCGCCATTCGAGTACCCACAGTCGCGGTTCTATCTAGTTACGCGTT AAACCAACTAGAA (SEQ ID NO: 1027), GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT147 / 235B1195.70202WO00#14468377 v2GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCAAT GCGACGGGTGTGGTGCGCTCGCCCTTCGAGTACCCACAGTCGCGGTTCTATCTAG TTACGCGTTAAACCAACTAGAA (SEQ ID NO: 1028), GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCAAT GCGACGGGTGTGGTGCGTTCGCCATTCGAGTACCCACAGTCGCGGTTCTATCTAG TTACGCGTTAAACCAACTAGAA (SEQ ID NO: 1029), GTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGTT GAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGGG TGTGGTACGCTCACCCTTCGAGTACCCACAGTCGCGGTTCTATCTAGTTACGCGTT AAACCAACTAGAA (SEQ ID NO: 1030), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG TACGCAGTCCATTCGAGTACCCACAGTCGCGGTTCTATCTAGTTACGCGTTAAAC CAACTAGAA (SEQ ID NO: 1031), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG TACGCAGTCCATTCGAGTACCCACAGCGCGGTTCTATCTAGTTACGCGTTAAACC AACTAGAA (SEQ ID NO: 1032), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG TACGCAGTCCATTCGAGTACCCACACGCGGTTCTATCTAGTTACGCGTTAAACCA ACTAGAA (SEQ ID NO: 1033), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGGTCGCCATTCGAGTACCCACAGTCGCGGTTCTATCTAGTTACGCG TTAAACCAACTAGAA (SEQ ID NO: 1034), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGGTCGCCATTCGAGTACCCACAGCGCGGTTCTATCTAGTTACGCGT TAAACCAACTAGAA (SEQ ID NO: 1035), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG148 / 235B1195.70202WO00#14468377 v2GTGTGGTACGGTCGCCATTCGAGTACCCACACGCGGTTCTATCTAGTTACGCGTT AAACCAACTAGAA (SEQ ID NO: 1036), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGTTCGCCATTCGAGTACCCACAGTCGCGGTTCTATCTAGTTACGCG TTAAACCAACTAGAA (SEQ ID NO: 1037), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGA CGGGTGTGGTACGTTCGCCATTCGAGTACCCACAGTCGCGGTTCTATCTAGTTAC GCGTTAAACCAACTAGAA (SEQ ID NO: 1038), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGTTCGCCATTCGAGTACCCACAGCGCGGTTCTATCTAGTTACGCGT TAAACCAACTAGAA (SEQ ID NO: 1039), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGGTCTCCATTCGAGTACCCACAGTCGCGGTTCTATCTAGTTACGCG TTAAACCAACTAGAA (SEQ ID NO: 1040), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGGTCTCCATTCGAGTACCCACAGCGCGGTTCTATCTAGTTACGCGT TAAACCAACTAGAA (SEQ ID NO: 1041), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG TACGCAGTCCCTTCGAGTACCCACAGTCGCGGTTCTATCTAGTTACGCGTTAAAC CAACTAGAA (SEQ ID NO: 1042), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGGTCTCCATTCGAGTACCCACACGCGGTTCTATCTAGTTACGCGTT AAACCAACTAGAA (SEQ ID NO: 1043), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG TACGCAGTCCCTTCGAGTACCCACAGCGCGGTTCTATCTAGTTACGCGTTAAACC149 / 235B1195.70202WO00#14468377 v2AACTAGAA (SEQ ID NO: 1044), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG TACGCAGTCCCTTCGAGTACCCACACGCGGTTCTATCTAGTTACGCGTTAAACCA ACTAGAA (SEQ ID NO: 1045), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGA CGGGTGTGGTACGTTCTCCATTCGAGTACCCACAGTCGCGGTTCTATCTAGTTAC GCGTTAAACCAACTAGAA (SEQ ID NO: 1046), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGA CGGGTGTGGTACGTTCTCCATTCGAGTACCCACAGCGCGGTTCTATCTAGTTACG CGTTAAACCAACTAGAA (SEQ ID NO: 1047), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGA CGGGTGTGGTACGTTCTCCATTCGAGTACCCACACGCGGTTCTATCTAGTTACGC GTTAAACCAACTAGAA (SEQ ID NO: 1048), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGTTCGCCTTTCGAGTACCCACAGTCGCGGTTCTATCTAGTTACGCGT TAAACCAACTAGAA (SEQ ID NO: 1049), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG TACGCAGTCCGTTCGAGTACCCACAGTCGCGGTTCTATCTAGTTACGCGTTAAACCAACTAGAA (SEQ ID NO: 1050), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGTTCGCCTTTCGAGTACCCACAGCGCGGTTCTATCTAGTTACGCGTT AAACCAACTAGAA (SEQ ID NO: 1051), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG TACGCAGTCCGTTCGAGTACCCACAGCGCGGTTCTATCTAGTTACGCGTTAAACC AACTAGAA (SEQ ID NO: 1052),150 / 235B1195.70202WO00#14468377 v2GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGTTCGCCTTTCGAGTACCCACACGCGGTTCTATCTAGTTACGCGTTA AACCAACTAGAA (SEQ ID NO: 1053), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG TACGCAGTCCGTTCGAGTACCCACACGCGGTTCTATCTAGTTACGCGTTAAACCA ACTAGAA (SEQ ID NO: 1054), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGATCGCCATTCGAGTACCCACAGTCGCGGTTCTATCTAGTTACGCG TTAAACCAACTAGAA (SEQ ID NO: 1055), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGCTCGCCTTTCGAGTACCCACAGTCGCGGTTCTATCTAGTTACGCG TTAAACCAACTAGAA (SEQ ID NO: 1056), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGATCGCCTTTCGAGTACCCACAGTCGCGGTTCTATCTAGTTACGCG TTAAACCAACTAGAA (SEQ ID NO: 1057), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGC GACGGGTGTGGTACGCTCGCCGTTCGAGTACCCACAGTCGCGGTTCTATCTAGTT ACGCGTTAAACCAACTAGAA (SEQ ID NO: 1058), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGA CGGGTGTGGTACGATCTCCATTCGAGTACCCACAGTCGCGGTTCTATCTAGTTAC GCGTTAAACCAACTAGAA (SEQ ID NO: 1059), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGGTCGCCTTTCGAGTACCCACAGTCGCGGTTCTATCTAGTTACGCG TTAAACCAACTAGAA (SEQ ID NO: 1060), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT151 / 235B1195.70202WO00#14468377 v2TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGC GACGGGTGTGGTACGGTCGCCGTTCGAGTACCCACAGTCGCGGTTCTATCTAGTT ACGCGTTAAACCAACTAGAA (SEQ ID NO: 1061), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGA CGGGTGTGGTACGTTCGCCGTTCGAGTACCCACAGTCGCGGTTCTATCTAGTTAC GCGTTAAACCAACTAGAA (SEQ ID NO: 1062), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGA CGGGTGTGGTACGATCGCCGTTCGAGTACCCACAGTCGCGGTTCTATCTAGTTAC GCGTTAAACCAACTAGAA (SEQ ID NO: 1063), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGGTCACCATTCGAGTACCCACAGTCGCGGTTCTATCTAGTTACGCG TTAAACCAACTAGAA (SEQ ID NO: 1064), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG TACGCAGTCCTTTCGAGTACCCACAGTCGCGGTTCTATCTAGTTACGCGTTAAAC CAACTAGAA (SEQ ID NO: 1065), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGTTCACCATTCGAGTACCCACAGTCGCGGTTCTATCTAGTTACGCG TTAAACCAACTAGAA (SEQ ID NO: 1066), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCAA TGCGACGGGTGTGGTGCGATCGCCATTCGAGTACCCACAGTCGCGGTTCTATCTA GTTACGCGTTAAACCAACTAGAA (SEQ ID NO: 1067), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGGTCACCCTTCGAGTACCCACAGTCGCGGTTCTATCTAGTTACGCG TTAAACCAACTAGAA (SEQ ID NO: 1068), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG152 / 235B1195.70202WO00#14468377 v2GTGTGGTACGATCACCATTCGAGTACCCACAGTCGCGGTTCTATCTAGTTACGCG TTAAACCAACTAGAA (SEQ ID NO: 1069), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGCTCTCCATTCGAGTACCCACAGTCGCGGTTCTATCTAGTTACGCG TTAAACCAACTAGAA (SEQ ID NO: 1070), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG TGTGGTACGCTCACCATTCGAGTACCCACAGTCGCGGTTCTATCTAGTTACGCGT TAAACCAACTAGAA (SEQ ID NO: 1071), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCAA TGCGACGGGTGTGGTACGATCACCCTTCGAGTACCCACAGTCGCGGTTCTATCTA GTTACGCGTTAAACCAACTAGAA (SEQ ID NO: 1072), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCAA TGCGACGGGTGTGGTGCGCTCGCCGTTCGAGTACCCACAGTCGCGGTTCTATCTA GTTACGCGTTAAACCAACTAGAA (SEQ ID NO: 1073), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCAA TGCGACGGGTGTGGTGCGCTCGCCATTCGAGTACCCACAGTCGCGGTTCTATCTA GTTACGCGTTAAACCAACTAGAA (SEQ ID NO: 1074), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG TGTGGTACGCTCGCCATTCGAGTACCCACAGTCGCGGTTCTATCTAGTTACGCGT TAAACCAACTAGAA (SEQ ID NO: 1075), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCAA TGCGACGGGTGTGGTGCGCTCGCCCTTCGAGTACCCACAGTCGCGGTTCTATCTA GTTACGCGTTAAACCAACTAGAA (SEQ ID NO: 1076), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCAA TGCGACGGGTGTGGTGCGTTCGCCATTCGAGTACCCACAGTCGCGGTTCTATCTA153 / 235B1195.70202WO00#14468377 v2GTTACGCGTTAAACCAACTAGAA (SEQ ID NO: 1077), GGTACTGTGGGTACTCGAAGGTTTCAGAGCTATGCTGGAAACAGCATAGCAAGT TGAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGCTCACCCTTCGAGTACCCACAGTCGCGGTTCTATCTAGTTACGCG TTAAACCAACTAGAA (SEQ ID NO: 1078), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGCAGTCCGTTCGAGTACCAAATGAAACCGCCATGTCCCTGGCGTTA AAGGGAA (SEQ ID NO: 1079), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGCAGTCCGTTCGAGTACCAAATCTTGCGCGGTTCGATCTAGTTACG CGTTAAACCAACTAGAA (SEQ ID NO: 1080), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGCAGTCCGTTCGAGTACCAATTTAACACGTCGTGCCGTACGGTAAA CGGCACA (SEQ ID NO: 1081), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGCAGTCCGTTCGAGTACCAAATCTTGCGAGGGTGCGGTTGGCCTCG TAAAAAGCCGCA (SEQ ID NO: 1082), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGCAGTCCGTTCGAGTACCAATTTAACAGTCCATGGTGAGGGGACTT GATACCTCACCG (SEQ ID NO: 1083), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGCTCACCGTTCGAGTACCAATTTAAACCGCCATGTCCCTGGCGTTA AAGGGAA (SEQ ID NO: 1084), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGCTCACCGTTCGAGTACCAATCTAAACGCGGTTCGATCTAGTTACG CGTTAAACCAACTAGAA (SEQ ID NO: 1085),154 / 235B1195.70202WO00#14468377 v2GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGCTCACCGTTCGAGTACCAAATCTAAACGTCGTGCCGTACGGTAAA CGGCACA (SEQ ID NO: 1086), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGCTCACCGTTCGAGTACCAATCTAAACGAGGGTGCGGTTGGCCTCG TAAAAAGCCGCA (SEQ ID NO: 1087), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAGCATAGCAAGT TTAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCGG GTGTGGTACGCTCACCGTTCGAGTACCAAATCTAAAGTCCATGGTGAGGGGACTT GATACCTCACCG (SEQ ID NO: 1088), GGTACTGTGGGTACTCGAAGGTTTAAGAGCTATGCTGGAAACAG...

Claims

CLAIMSWhat is claimed is:

1. A prime editing guide RNA (pegRNA) comprising an edit template comprising a sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to, or comprising one, two, three, four, or five mutations relative to, the sequence of any one of SEQ ID NOs: 12-184, or the sequence CAGTCCTTT, CTCTCCTTT, or GCAGTCCGT.

2. The pegRNA of claim 1, wherein the pegRNA comprises an edit template comprising the sequence of any one of SEQ ID NOs: 12-184, or the sequence CAGTCCTTT, CTCTCCTTT, or GCAGTCCGT.

3. The pegRNA of claim 1 or 2, wherein the pegRNA comprises an edit template comprising a sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to, or comprising one, two, three, four, or five mutations relative to, the sequence of SEQ ID NO: 148.

4. The pegRNA of any one of claims 1-3, wherein the pegRNA comprises an edit template comprising the sequence of SEQ ID NO: 148.

5. The pegRNA of any one of claims 1-4, wherein the pegRNA comprises a spacer sequence comprising a sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to, or comprising one, two, three, four, or five mutations relative to, the sequence of any one of SEQ ID NOs: 185-284.

6. The pegRNA of any one of claims 1-5, wherein the pegRNA comprises a spacer sequence comprising the sequence of any one of SEQ ID NOs: 185-284.

7. The pegRNA of any one of claims 1-6, wherein the pegRNA comprises a spacer sequence comprising a sequence at least 80%, at least 85%, at least 90%, at least 95%, at212 / 235B1195.70202WO00#14468377 v2least 96%, at least 97%, at least 98%, or at least 99% identical to, or comprising one, two, three, four, or five mutations relative to, the sequence of SEQ ID NO: 189.

8. The pegRNA of any one of claims 1-7, wherein the pegRNA comprises a spacer sequence comprising the sequence of SEQ ID NO: 189.

9. The pegRNA of any one of claims 1-8, wherein the pegRNA comprises a backbone scaffold comprising a sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to, or comprising one, two, three, four, or five mutations relative to, the sequence of any one of SEQ ID NOs: 285-287.

10. The pegRNA of any one of claims 1-9, wherein the pegRNA comprises a backbone scaffold comprising the sequence of any one of SEQ ID NOs: 285-287.

11. The pegRNA of any one of claims 1-10, wherein the pegRNA comprises a backbone scaffold comprising a sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to, or comprising one, two, three, four, or five mutations relative to, the sequence of SEQ ID NO: 285.

12. The pegRNA of any one of claims 1-11, wherein the pegRNA comprises a backbone scaffold comprising the sequence of SEQ ID NO: 285.

13. The pegRNA of any one of claims 1-12, wherein the pegRNA comprises a primer binding site (PBS) comprising a sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to, or comprising one, two, three, four, or five mutations relative to, the sequence of any one of SEQ ID NOs: 288-297, or the sequence CGAGTACCC or CGAGTACC.

14. The pegRNA of any one of claims 1-13, wherein the pegRNA comprises a PBS comprising the sequence of any one of SEQ ID NOs: 288-297, or the sequence CGAGTACCC or CGAGTACC.213 / 235B1195.70202WO00#14468377 v215. The pegRNA of any one of claims 1-14, wherein the pegRNA comprises a PBS comprising a sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to, or comprising one, two, three, four, or five mutations relative to, the sequence of CGAGTACC or CGAGTACCC.

16. The pegRNA of any one of claims 1-15, wherein the pegRNA comprises a PBS comprising the sequence of CGAGTACC or CGAGTACCC.

17. The pegRNA of any one of claims 1-16, wherein the pegRNA further comprises a structured motif at the 3 ' end.

18. The pegRNA of claim 17, wherein the structured motif is an RNA pseudoknot motif.

19. The pegRNA of claim 17 or 18, wherein the structured motif comprises a sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to, or comprising one, two, three, four, or five mutations relative to, the sequence of SEQ ID NO: 298, 301, 302, or 1295-1319.

20. The pegRNA of any one of claims 17-19, wherein the structured motif comprises the sequence of SEQ ID NO: 298, 301, 302, or 1295-1319.

21. The pegRNA of any one of claims 17-20, wherein the structured motif comprises a sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to, or comprising one, two, three, four, or five mutations relative to, the sequence of SEQ ID NO: 1301 or 1307.

22. The pegRNA of any one of claims 17-21, wherein the structured motif comprises the sequence of SEQ ID NO: 1301 or 1307.

23. The pegRNA of any one of claims 17-22, wherein the pegRNA comprises a linker connecting the structured motif to the 3 ' end.214 / 235B1195.70202WO00#14468377 v224. The pegRNA of claim 23, wherein the linker comprises a sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to, or comprising one, two, three, four, or five mutations relative to, the sequence of any one of TGAAAGTC, AAATTAAC, TGCCCAAC, TGCCATCC, TGATCCCT, TTCTCTCA, TGATCCAA, TAACCAAT, TGATCCAC, TATTTAAA, TTTCCTCA, TTCCTCTA, TTCTCCTC, AAAGGATA, CAATTAAT, CATTAAGC, TCCCTTCC, TCCTGAAT, TCCTTAAT, CCAATATC, CTTCCTCT, CCAATTCC, TCCCTTCT, TCAAATCT, TCCTAAAT, AAAGATAA, AAAGAATG, AAAGAATA, CTTCCCAT, CCTGTTCA, GAGAATAG, GAGAACCT, CCTCCATT, CAGAGAAT, CCTCCGAA, CCTAAAGG, CTTAGTAA, AATATAAC, AATAAGTC, ATATAAAC, ATCATAAT, GAAAGAAG, ATCAGATA, ATAATAAT, GATTAATA, GATCCATA, ATTCCGAC, GAGAAGAA, GGATAATC, AATTAATA, TAATAATG, TAATAAAC, TTTCCGAC, TTCTCCAC, TGAATCCA, TAATAATA, TTCCATCA, TGATCATA, TTCCTCCT, TGATCCAT, TTCTCCGA, AAAGGATT, CAATAATA, CACCTATC, CCTTTCGA, CCTTTAAC, TCCAAGAG, CAATCAAC, TAATAGAA, CCAATCCA, TTCCAAAT, TCCAATCC, TTCAAATT, CAAGGAGA, AAGAGAAA, AAAGATTT, CGAGAAAT, CCGTCCGA, CGAAGAAG, GAGGACCA, AAGAAATA, AGAAGATC, AAGAAGAA, CCGGAGAC, CCGTTCAT, AATAATTT, AGATAAAT, AAGATCCA, AGAAGAAT, AGAAGAAG, AGGAATGA, AATAAATT, AGATCCCT, AATTCAAT, AATATTTC, AGAAGTAT, GGGCTACC, TAATAATT, GGATTAAA, CACTGTAG, ACCATTAG, CCATTTAG, GTTAACCA, TTCTAAAC, ATTTCCAT, CCTTAAAG, CCCAAGAT, GAGTTCAA, GTGTCCCA, TGATAAAC, ATAATTTA, CCTGTCTA, AGATCCTT, TAATCCCT, AATAATCC, CTTCCTTA, AATTAATG, CCTTCAAA, AAATAAAG, TGTTCAAC, AATAAAGA, CGCCTAAT, AACTGTTA, CCATCCAC, ATCCATTT, CCAAATTT, ATTTAATC, CCTTCCAC, GGATATCC, TGTCCAAG, GCGCCCTC, CACCTGTA, ACCATTAA, CCATATCT, AATCTAAT, TAAATCTG, AACCTTCT, CCTTTAAT, ATTAATTC, CCAAATCG, ATTTCCTA, TAATCCTT, AATCAATC, CTTCCCGC, CCCTTTCT, CCTTCTAA, GTCTATCC, TGATAAAG, AATGAATA, CTTTAAAG, CCCTTAGC, CCAAGAAT, AAATTTCA, TGAATCCT, AATCCTAT, CCATTCCT, CCTTAATC, AATCTCTT, TGATCCTC, ATTAAATA, TTCAATTC, ATTAAGAA, CCTAGAAA, AAATCCTA, TTCCTAAA, ATCTCTCT, TTCCTTAA, ATTTCCGC, GTTTAAAC, AATTTAAC, TCATTTCA, CAAATTAG, GAATTTAA, GTTAAATC, TTCCTAAC, ATCCTTAA, TCCCTGAG, AATAGAGG, CCTGATAT,215 / 235B1195.70202WO00#14468377 v2GTTAAACC, TTCCCTTC, AATCTTCG, TCCCTGAT, ATTTCCCT, CCTTAGAC, GTTAACCG, GTCTCCTC, GTCTCCCT, AAATTAAT, TTCTAATC, TTTCCTAA, TGATTCAA, TGAATTCC, TTCCCATA, ATCCAAAT, AATGAAGT, ATTCCGAA, AATTTAAG, CTCCCGAC, TTCAATGA, TCATGAAT, TAATAAAT, AATTAATT, GTCTAAAC, AATCTAAA, AAATTGAT, AGAAATGT, GTCTGAAA, TTTCATAA, TGAATAAA, TGATAATA, TGTTAAAC, TTCTCAAA, TTCTAATA, ATAAAGAG, AACTTAAA, AATTGATA, ATTAAAGT, AACGAAAT, ATTAATAA, TTCAATAT, TCATAGAG, CTTTAAAC, TCTTTAAA, TAAAGAAT, TCTTAAAT, GTCTTCCA, AAATCTTC, GTTAAATA, GTCTTAAC, GTTCTAAA, AATCTTAA, AAATCCTG, AATCCCTT, AGACCCGT, AGAAATTT, AGAAATTG, TCCTCTTA, TTTAATAA, TAAATTTA, TTCTTCAC, AATTTAAT, TGAAATTA, TAAATTGA, TAAATTAA, TTAAATGA, TGAAATAA, TAATTGAA, TGAATAAC, TTCTGAAC, TGAATGAA, TGAAATGA, TTCTTCAA, AATTAAAT, TCCTCTTC, TCCTAATA, TAAATGAG, TGAATTAA, TTCCATTA, TCCTCATT, TATTAAAT, TAATTAAG, TTAATGAA, TGATGAAC, TATTTAAC, TATTCAAT, TTCGAAAC, TAAATAAA, TAATGAAA, TTTCTAAA, TTGATAAC, TTCTTAAC, TCCTCAAA, AATAAATG, TCCTTCAC, TCCTGAAC, TGATTAAC, TTCTAAAG, AGAAATAA, AAATGAAT, ATCCTGAC, ATTCTAAA, GTCTAAAT, AAATTCTC, AAATTTAT, ATTAAATT, ATTCCTTA, AAATCTTG, AATCTTCA, AATTTAAA, GTCTAATA, GTGAAATA, GTTGAAAC, ATTTAATA, AGAAATTC, AATCTCTC, GTAAATTA, AAATGAAA, AATTTCTC, AATTAAAG, AAATTAAA, ATTTAAAG, AAATTTAA, AAATCTTA, AGAAATTA, AATCTAAG, AAATTCTA, ATTCTAAG, AAATTCGT, ATCCTTTA, ATTAATTA, AATCTGAT, AAATCTCA, ATTAATGA, ATTTAAAT, ATCTAATG, ATTCTTAA, AAATCTTT, GTAAATGA, AAATTCGA, AAATTAAG, AGATGAAA, GTTAATAA, AGAAATGA, GTGATAAA, AATTAATC, GTTCTAAC, AAATTCTG, AAATTGAA, AAATCTAA, AATTCTTA, GTTAAACA, TTTATAAC, AACGAATA, ATAAAGAA, AATAATGA, ATTTAAGC, AATAAGAA, AATTAAAC, AGATTTAA, ATCTTCGA, TCCTTAAA, TGATAAGC, TAAATTAT, TAAATTAG, AATAAGAG, AATAAATA, AATAATTC, AATATGAG, ATTAATAT, AATTCGTC, ACACCCGT, AATCTTTA, AATGAAAT, GATTAAGA, AAATAATG, TAAATGAA, TAAATGAC, GAAATTTA, GAAATTTC, ATTAAATG, ATTAATAC, GAAATAAT, AACGATGA, ATAAATAA, AGATCTTG, AGTTTAAC, AAAACTTG, AAAAGAAA, AACACTTG, AACAGAAA, AACATAAC, TCATGAAA, TCATTCAA, TCTATAAC, GCTTAAGA, ACATAATG,216 / 235B1195.70202WO00#14468377 v2TCAATGAA, ATGAAATG, ATGAATAC, AAGATAAC, GAGATAAT, AAGGATGA, ATGAATAA, TAAGGAAA, TGAGTCAA, TTTGTAAC, GATGAAGA, TAAGTGAA, ATTTAATG, ATTTATAC, GAATTAAT, AACTATGA, ATATATAA, TTATGAAA, TAATTAAA, TTAATAAC, TGATTAAA, TAAATAAG, TGAATAGA, TTACTAAA, TTATTAAA, TAGTGAAA, TTTAGAAC, TGGTTCAA, TAGATGAG, TGGAATGA, TTTCGAAA, or TTGTGAAA.

25. The pegRNA of claim 23 or 24, wherein the linker comprises the sequence of any one of SEQ ID NOs: TGAAAGTC, AAATTAAC, TGCCCAAC, TGCCATCC, TGATCCCT, TTCTCTCA, TGATCCAA, TAACCAAT, TGATCCAC, TATTTAAA, TTTCCTCA, TTCCTCTA, TTCTCCTC, AAAGGATA, CAATTAAT, CATTAAGC, TCCCTTCC, TCCTGAAT, TCCTTAAT, CCAATATC, CTTCCTCT, CCAATTCC, TCCCTTCT, TCAAATCT, TCCTAAAT, AAAGATAA, AAAGAATG, AAAGAATA, CTTCCCAT, CCTGTTCA, GAGAATAG, GAGAACCT, CCTCCATT, CAGAGAAT, CCTCCGAA, CCTAAAGG, CTTAGTAA, AATATAAC, AATAAGTC, ATATAAAC, ATCATAAT, GAAAGAAG, ATCAGATA, ATAATAAT, GATTAATA, GATCCATA, ATTCCGAC, GAGAAGAA, GGATAATC, AATTAATA, TAATAATG, TAATAAAC, TTTCCGAC, TTCTCCAC, TGAATCCA, TAATAATA, TTCCATCA, TGATCATA, TTCCTCCT, TGATCCAT, TTCTCCGA, AAAGGATT, CAATAATA, CACCTATC, CCTTTCGA, CCTTTAAC, TCCAAGAG, CAATCAAC, TAATAGAA, CCAATCCA, TTCCAAAT, TCCAATCC, TTCAAATT, CAAGGAGA, AAGAGAAA, AAAGATTT, CGAGAAAT, CCGTCCGA, CGAAGAAG, GAGGACCA, AAGAAATA, AGAAGATC, AAGAAGAA, CCGGAGAC, CCGTTCAT, AATAATTT, AGATAAAT, AAGATCCA, AGAAGAAT, AGAAGAAG, AGGAATGA, AATAAATT, AGATCCCT, AATTCAAT, AATATTTC, AGAAGTAT, GGGCTACC, TAATAATT, GGATTAAA, CACTGTAG, ACCATTAG, CCATTTAG, GTTAACCA, TTCTAAAC, ATTTCCAT, CCTTAAAG, CCCAAGAT, GAGTTCAA, GTGTCCCA, TGATAAAC, ATAATTTA, CCTGTCTA, AGATCCTT, TAATCCCT, AATAATCC, CTTCCTTA, AATTAATG, CCTTCAAA, AAATAAAG, TGTTCAAC, AATAAAGA, CGCCTAAT, AACTGTTA, CCATCCAC, ATCCATTT, CCAAATTT, ATTTAATC, CCTTCCAC, GGATATCC, TGTCCAAG, GCGCCCTC, CACCTGTA, ACCATTAA, CCATATCT, AATCTAAT, TAAATCTG, AACCTTCT, CCTTTAAT, ATTAATTC, CCAAATCG, ATTTCCTA, TAATCCTT, AATCAATC, CTTCCCGC, CCCTTTCT, CCTTCTAA, GTCTATCC, TGATAAAG, AATGAATA,217 / 235B1195.70202WO00#14468377 v2CTTTAAAG, CCCTTAGC, CCAAGAAT, AAATTTCA, TGAATCCT, AATCCTAT, CCATTCCT, CCTTAATC, AATCTCTT, TGATCCTC, ATTAAATA, TTCAATTC, ATTAAGAA, CCTAGAAA, AAATCCTA, TTCCTAAA, ATCTCTCT, TTCCTTAA, ATTTCCGC, GTTTAAAC, AATTTAAC, TCATTTCA, CAAATTAG, GAATTTAA, GTTAAATC, TTCCTAAC, ATCCTTAA, TCCCTGAG, AATAGAGG, CCTGATAT, GTTAAACC, TTCCCTTC, AATCTTCG, TCCCTGAT, ATTTCCCT, CCTTAGAC, GTTAACCG, GTCTCCTC, GTCTCCCT, AAATTAAT, TTCTAATC, TTTCCTAA, TGATTCAA, TGAATTCC, TTCCCATA, ATCCAAAT, AATGAAGT, ATTCCGAA, AATTTAAG, CTCCCGAC, TTCAATGA, TCATGAAT, TAATAAAT, AATTAATT, GTCTAAAC, AATCTAAA, AAATTGAT, AGAAATGT, GTCTGAAA, TTTCATAA, TGAATAAA, TGATAATA, TGTTAAAC, TTCTCAAA, TTCTAATA, ATAAAGAG, AACTTAAA, AATTGATA, ATTAAAGT, AACGAAAT, ATTAATAA, TTCAATAT, TCATAGAG, CTTTAAAC, TCTTTAAA, TAAAGAAT, TCTTAAAT, GTCTTCCA, AAATCTTC, GTTAAATA, GTCTTAAC, GTTCTAAA, AATCTTAA, AAATCCTG, AATCCCTT, AGACCCGT, AGAAATTT, AGAAATTG, TCCTCTTA, TTTAATAA, TAAATTTA, TTCTTCAC, AATTTAAT, TGAAATTA, TAAATTGA, TAAATTAA, TTAAATGA, TGAAATAA, TAATTGAA, TGAATAAC, TTCTGAAC, TGAATGAA, TGAAATGA, TTCTTCAA, AATTAAAT, TCCTCTTC, TCCTAATA, TAAATGAG, TGAATTAA, TTCCATTA, TCCTCATT, TATTAAAT, TAATTAAG, TTAATGAA, TGATGAAC, TATTTAAC, TATTCAAT, TTCGAAAC, TAAATAAA, TAATGAAA, TTTCTAAA, TTGATAAC, TTCTTAAC, TCCTCAAA, AATAAATG, TCCTTCAC, TCCTGAAC, TGATTAAC, TTCTAAAG, AGAAATAA, AAATGAAT, ATCCTGAC, ATTCTAAA, GTCTAAAT, AAATTCTC, AAATTTAT, ATTAAATT, ATTCCTTA, AAATCTTG, AATCTTCA, AATTTAAA, GTCTAATA, GTGAAATA, GTTGAAAC, ATTTAATA, AGAAATTC, AATCTCTC, GTAAATTA, AAATGAAA, AATTTCTC, AATTAAAG, AAATTAAA, ATTTAAAG, AAATTTAA, AAATCTTA, AGAAATTA, AATCTAAG, AAATTCTA, ATTCTAAG, AAATTCGT, ATCCTTTA, ATTAATTA, AATCTGAT, AAATCTCA, ATTAATGA, ATTTAAAT, ATCTAATG, ATTCTTAA, AAATCTTT, GTAAATGA, AAATTCGA, AAATTAAG, AGATGAAA, GTTAATAA, AGAAATGA, GTGATAAA, AATTAATC, GTTCTAAC, AAATTCTG, AAATTGAA, AAATCTAA, AATTCTTA, GTTAAACA, TTTATAAC, AACGAATA, ATAAAGAA, AATAATGA, ATTTAAGC, AATAAGAA, AATTAAAC, AGATTTAA, ATCTTCGA, TCCTTAAA, TGATAAGC, TAAATTAT, TAAATTAG, AATAAGAG, AATAAATA,218 / 235B1195.70202WO00#14468377 v2AATAATTC, AATATGAG, ATTAATAT, AATTCGTC, ACACCCGT, AATCTTTA, AATGAAAT, GATTAAGA, AAATAATG, TAAATGAA, TAAATGAC, GAAATTTA, GAAATTTC, ATTAAATG, ATTAATAC, GAAATAAT, AACGATGA, ATAAATAA, AGATCTTG, AGTTTAAC, AAAACTTG, AAAAGAAA, AACACTTG, AACAGAAA, AACATAAC, TCATGAAA, TCATTCAA, TCTATAAC, GCTTAAGA, ACATAATG, TCAATGAA, ATGAAATG, ATGAATAC, AAGATAAC, GAGATAAT, AAGGATGA, ATGAATAA, TAAGGAAA, TGAGTCAA, TTTGTAAC, GATGAAGA, TAAGTGAA, ATTTAATG, ATTTATAC, GAATTAAT, AACTATGA, ATATATAA, TTATGAAA, TAATTAAA, TTAATAAC, TGATTAAA, TAAATAAG, TGAATAGA, TTACTAAA, TTATTAAA, TAGTGAAA, TTTAGAAC, TGGTTCAA, TAGATGAG, TGGAATGA, TTTCGAAA, or TTGTGAAA.

26. The pegRNA of any one of claims 23-25, wherein the linker comprises a sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to, or comprising one, two, three, four, or five mutations relative to, the sequence TGAAATGA, TTACTAAA, AAATCTTG, TAATGAAA, or TCTATAAC.

27. The pegRNA of any one of claims 23-26, wherein the linker comprises the sequence TGAAATGA, TTACTAAA, AAATCTTG, TAATGAAA, or TCTATAAC.

28. The pegRNA of any one of claims 1-27, wherein the pegRNA comprises the structure: 5 '-[spacer] -[backbone scaffold] -[edit template] -[primer binding site] -[linker] -[structured motif] -3'.

29. The pegRNA of any one of claims 1-28, wherein the pegRNA comprises a sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to, or comprising one, two, three, four, or five mutations relative to, the sequence of any one of SEQ ID NOs: 304-1256, 1320, and 1423-1510.

30. The pegRNA of any one of claims 1-29, wherein the pegRNA comprises the sequence of any one of SEQ ID NOs: 304-1256, 1320, and 1423-1510.219 / 235B1195.70202WO00#14468377 v231. The pegRNA of any one of claims 1-30, wherein the pegRNA comprises a sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to, or comprising one, two, three, four, or five mutations relative to, the sequence of SEQ ID NO: 889, 1093, 1211, 1432, or 1465.

32. The pegRNA of any one of claims 1-31, wherein the pegRNA comprises the sequence of SEQ ID NO: 889, 1093, 1211, 1432, or 1465.

33. A prime editing guide RNA (pegRNA) comprising a spacer sequence comprising a sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to, or comprising one, two, three, four, or five mutations relative to, the sequence of any one of SEQ ID NOs: 185-284.

34. A prime editing guide RNA (pegRNA) comprising a primer binding site (PBS) comprising a sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to, or comprising one, two, three, four, or five mutations relative to, the sequence of any one of SEQ ID NOs: 288-297, or the sequence CGAGTACCC or CGAGTACC.

35. A nicking guide RNA (ngRNA) comprising a spacer comprising a sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to, or comprising one, two, three, four, or five mutations relative to, the sequence of any one of SEQ ID NOs: 1257-1275.

36. The ngRNA of claim 35, wherein the ngRNA comprises a spacer comprising the sequence of any one of SEQ ID NOs: 1257-1275.

37. The ngRNA of claim 35 or 36, wherein the ngRNA comprises a spacer comprising a sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to, or comprising one, two, three, four, or five mutations relative to, the sequence of SEQ ID NO: 1275.220 / 235B1195.70202WO00#14468377 v238. The ngRNA of any one of claims 35-37, wherein the ngRNA comprises a spacer comprising the sequence of SEQ ID NO: 1275.

39. The ngRNA of any one of claims 35-38, wherein the ngRNA comprises a backbone scaffold comprising a sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to, or comprising one, two, three, four, or five mutations relative to, the sequence of SEQ ID NO: 285.

40. The ngRNA of any one of claims 35-39, wherein the ngRNA comprises a backbone scaffold comprising the sequence of SEQ ID NO: 285.

41. The ngRNA of any one of claims 35-40, wherein the ngRNA comprises a sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to, or comprising one, two, three, four, or five mutations relative to, the sequence of any one of SEQ ID NOs: 1276-1294.

42. The ngRNA of any one of claims 35-41, wherein the pegRNA comprises the sequence of any one of SEQ ID NOs: 1276-1294.

43. The ngRNA of any one of claims 35-42, wherein the pegRNA comprises a sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to, or comprising one, two, three, four, or five mutations relative to, the sequence of SEQ ID NO: 1279.

44. The ngRNA of any one of claims 35-43, wherein the pegRNA comprises the sequence of SEQ ID NO: 1279.

45. A method of prime editing a RHO gene comprising contacting a nucleic acid sequence encoding the RHO gene with a prime editor and a pegRNA of any one of claims 1-34.

46. The method of claim 45 further comprising providing a nicking guide RNA (ngRNA).221 / 235B1195.70202WO00#14468377 v247. The method of claim 46, wherein the ngRNA is an ngRNA of any one of claims 35-44.

48. The method of any one of claims 45-47, wherein the prime editor comprises a nucleic acid-programmable DNA-binding protein (napDNAbp) and a polymerase.

49. The method of claim 48, wherein the napDNAbp comprises a Cas9 protein.

50. The method of claim 48 or 49, wherein the napDNAbp comprises a Cas9 nickase (nCas9).

51. The method of claim 49 or 50, wherein the Cas9 protein is a Streptococcus pyogenes Cas9 protein, or a variant thereof.

52. The method of any one of claims 45-51, wherein the polymerase is a reverse transcriptase.

53. The method of claim 52, wherein the reverse transcriptase comprises an MMLV reverse transcriptase, a Tfl reverse transcriptase, or a variant thereof.

54. The method of any one of claims 45-53, wherein the prime editor comprises PEmax architecture.

55. The method of any one of claims 45-54, wherein the prime editor is a PE6 prime editor.

56. The method of any one of claims 45-55, wherein the prime editor is PE6b, PE6e, or PE6g.

57. The method of any one of claims 45-56, wherein the prime editor is PE6g.

58. The method of any one of claims 45-57, wherein the prime editor is expressed from a polynucleotide.222 / 235B1195.70202WO00#14468377 v259. The method of any one of claims 45-58, wherein the step of contacting corrects a P23H mutation in a rhodopsin protein encoded by the RHO gene.

60. The method of any one of claims 45-59, wherein the step of contacting results in the correction of an A: T base pair to a C: G base pair at nucleotide position 68 in the RHO gene.

61. The method of any one of claims 45-60, wherein the step of contacting results in the correction of the RHO gene to a wild-type sequence.

62. The method of any one of claims 45-61, wherein the step of contacting results in at least 40%, at least 45%, at least 50%, at least 55%, or at least 60% correction of the RHO gene to a wild-type sequence within a cell or a population of cells.

63. The method of any one of claims 45-62, wherein the step of contacting results in less than 15%, less than 14%, less than 13%, less than 12%, less than 11%, or less than 10% introduction of indels into the genome of a cell or a population of cells.

64. The method of any one of claims 45-63, wherein the step of contacting results in the installation of one or more silent edits into the RHO gene.

65. The method of claim 64, wherein the one or more silent edits include changing a C: G base pair to a T: A base pair at nucleotide position 66 in the RHO gene.

66. The method of claim 64 or 65, wherein the one or more silent edits include changing a C: G base pair to a G: C base pair at nucleotide position 69 in the RHO gene.

67. The method of any one of claims 45-66, wherein the contacting is performed in a cell.

68. The method of claim 67, wherein the cell is a retinal pigment epithelium (RPE) cell.

69. The method of any one of claims 45-68, wherein the contacting is performed in vivo.223 / 235B1195.70202WO00#14468377 v270. The method of any one of claims 45-68, wherein the contacting is performed in vitro.

71. The method of any one of claims 45-69, wherein the contacting is performed in a subject.

72. The method of claim 71, wherein the subject is a human.

73. The method of any one of claims 45-72, wherein the RHO gene is a human RHO gene.

74. The method of any one of claims 45-73, wherein the method is a method of treating or preventing retinitis pigmentosa in a subject.

75. The method of any one of claims 71-74, wherein the prime editor and / or the pegRNA are administered to the subject via subretinal injection.

76. The method of any one of claims 45-75, wherein the prime editor and the pegRNA are delivered to the cell via AAV.

77. The method of claim 76, wherein the AAV is AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, or AAV9.

78. The method of claim 76 or 77, wherein the AAV is AAV5.

79. The method of any one of claims 76-78, wherein the AAV is encoded by the v3em vector.

80. A method of treating or preventing retinitis pigmentosa in a subject, the method comprising administering to the subject a prime editor and a pegRNA of any one of claims 1-34, and optionally a ngRNA of any one of claims 35-44.224 / 235B1195.70202WO00#14468377 v281. A system comprising the pegRNA of any one of claims 1-34 and / or the ngRNA of any one of claims 35-44.

82. The system of claim 81 further comprising a prime editor.

83. The system of claim 81 further comprising a polynucleotide encoding a prime editor.

84. The system of claim 82 or 83, wherein the prime editor comprises a nucleic acid-programmable DNA-binding protein (napDNAbp) and a polymerase.

85. The system of claim 84, wherein the napDNAbp comprises a Cas9 protein.

86. The system of claim 84 or 85, wherein the napDNAbp comprises a Cas9 nickase (nCas9).

87. The system of claim 85 or 86, wherein the Cas9 protein is a Streptococcus pyogenes Cas9 protein, or a variant thereof.

88. The system of any one of claims 84-87, wherein the polymerase is a reverse transcriptase.

89. The system of claim 88, wherein the reverse transcriptase is an MMLV reverse transcriptase, a Tf 1 reverse transcriptase, or a variant thereof.

90. The system of any one of claims 82-89, wherein the prime editor comprises PEmax architecture.

91. The system of any one of claims 82-90, wherein the prime editor is a PE6 prime editor.

92. The system of any one of claims 82-91, wherein the prime editor is PE6b, PE6e, or PE6g.225 / 235B1195.70202WO00#14468377 v293. The system of any one of claims 82-92, wherein the prime editor is PE6g.

94. A complex comprising a prime editor and the pegRNA of any one of claims 1-34 or the ngRNA of any one of claims 35-44.

95. A composition comprising the pegRNA of any one of claims 1-34 and / or the ngRNA of any one of claims 35-44, and an excipient.

96. A polynucleotide encoding the pegRNA of any one of claims 1-34 and / or the ngRNA of any one of claims 35-44.

97. One or more polynucleotides encoding the system of any one of claims 81-93, the complex of claim 94, or the composition of claim 95.

98. A vector comprising a polynucleotide of claim 96.

99. One or more vectors comprising the one or more polynucleotides of claim 97.

100. An AAV comprising a polynucleotide encoding the pegRNA of any one of claims 1-34, the ngRNA of any one of claims 35-44, the system of any one of claims 81-93, the complex of claim 94, and / or the composition of claim 95, or comprising the one or more polynucleotides of claim 96 or 97.

101. The AAV of claim 100, wherein the AAV is AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, or AAV9.

102. The AAV of claim 100 or 101, wherein the AAV is AAV5.

103. The AAV of any one of claims 100-102, wherein the AAV is encoded by the v3em vector.

104. A pharmaceutical composition comprising the pegRNA of any one of claims 1-34, the ngRNA of any one of claims 35-44, the system of any one of claims 81-93, the complex of 226 / 235B1195.70202WO00#14468377 v2claim 94, the composition of claim 95, the one or more polynucleotides of claim 96 or 97, and / or the one or more vectors of claim 98 or 99.

105. A cell comprising the pegRNA of any one of claims 1-34, the ngRNA of any one of claims 35-44, the system of any one of claims 81-93, the complex of claim 94, the composition of claim 95, the one or more polynucleotides of claim 96 or 97, the one or more vectors of claim 98 or 99, and / or the AAV of any one of claims 100-103.

106. A kit comprising the pegRNA of any one of claims 1-34, the ngRNA of any one of claims 35-44, the system of any one of claims 81-93, the complex of claim 94, the composition of claim 95, the one or more polynucleotides of claim 96 or 97, the one or more vectors of claim 98 or 99, and / or the AAV of any one of claims 100-103.

107. Use of the pegRNA of any one of claims 1-34, the ngRNA of any one of claims 35-44, the system of any one of claims 81-93, the complex of claim 94, the composition of claim 95, the one or more polynucleotides of claim 96 or 97, the one or more vectors of claim 98 or 99, and / or the AAV of any one of claims 100-103 in the manufacture of a medicament for the treatment of retinitis pigmentosa.

108. The pegRNA of any one of claims 1-34, the ngRNA of any one of claims 35-44, the system of any one of claims 81-93, the complex of claim 94, the composition of claim 95, the one or more polynucleotides of claim 96 or 97, the one or more vectors of claim 98 or 99, and / or the AAV of any one of claims 100-103 for use in medicine.

109. A prime editing guide RNA (pegRNA) comprising an edit template comprising a sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to, or comprising one, two, three, four, or five mutations relative to, the sequence of SEQ ID NO: 184.

110. The pegRNA of claim 109, wherein the pegRNA comprises an edit template comprising the sequence of SEQ ID NO: 184.227 / 235B1195.70202WO00#14468377 v2111. The pegRNA of claim 109 or 110, wherein the pegRNA comprises a spacer sequence comprising a sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to, or comprising one, two, three, four, or five mutations relative to, the sequence of SEQ ID NO: 185.

112. The pegRNA of any one of claims 109-111, wherein the pegRNA comprises a spacer sequence comprising the sequence of SEQ ID NO: 185.

113. The pegRNA of any one of claims 109-112, wherein the pegRNA comprises a backbone scaffold comprising a sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to, or comprising one, two, three, four, or five mutations relative to, the sequence of SEQ ID NO: 285.

114. The pegRNA of any one of claims 109-113, wherein the pegRNA comprises a backbone scaffold comprising the sequence of SEQ ID NO: 285.

115. The pegRNA of any one of claims 109-114, wherein the pegRNA comprises a PBS comprising a sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to, or comprising one, two, three, four, or five mutations relative to, the sequence of SEQ ID NO: 288.

116. The pegRNA of any one of claims 109-115, wherein the pegRNA comprises a PBS comprising the sequence of SEQ ID NO: 288.

117. The pegRNA of any one of claims 109-116, wherein the pegRNA further comprises a structured motif at the 3 ' end.

118. The pegRNA of claim 117, wherein the structured motif is an RNA pseudoknot motif.

119. The pegRNA of claim 117 or 118, wherein the structured motif comprises a sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to, or comprising one, two, three, four, or five mutations relative to,228 / 235B1195.70202WO00#14468377 v2the sequence CGCGGTTCTATCTAGTTACGCGTTAAACCAACTAGAA (SEQ ID NO: 298).

120. The pegRNA of any one of claims 117-119, wherein the structured motif comprises the sequence CGCGGTTCTATCTAGTTACGCGTTAAACCAACTAGAA (SEQ ID NO: 298).

121. The pegRNA of claim 117 or 118, wherein the structured motif comprises a sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to, or comprising one, two, three, four, or five mutations relative to, the sequence AAGTCCATGGTGAGGGGACTTGATACCTCACCG (SEQ ID NO: 1301).

122. The pegRNA of claim 117, 118, or 121, wherein the structured motif comprises the sequence AAGTCCATGGTGAGGGGACTTGATACCTCACCG (SEQ ID NO: 1301).

123. The pegRNA of claim 117 or 118, wherein the structured motif comprises a sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to, or comprising one, two, three, four, or five mutations relative to, the sequence GCCGGGCGCGGTGGCGCGTGCCTGTAGTCCCAGCTACTCGGGAGGCT (SEQ ID NO: 1307).

124. The pegRNA of any one of claims 117, 118, or 123, wherein the structured motif comprises the sequence GCCGGGCGCGGTGGCGCGTGCCTGTAGTCCCAGCTACTCGGGAGGCT (SEQ ID NO: 1307).

125. The pegRNA of any one of claims 117-124, wherein the pegRNA comprises a linker connecting the structured motif to the 3 ' end.

126. The pegRNA of claim 125, wherein the linker comprises a sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to, or comprising one, two, three, four, or five mutations relative to, the sequence TGAAAGTC.229 / 235B1195.70202WO00#14468377 v2127. The pegRNA of claim 125 or 126, wherein the linker comprises the sequence TGAAAGTC.

128. The pegRNA of claim 125, wherein the linker comprises a sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to, or comprising one, two, three, four, or five mutations relative to, the sequence TGAAATGA.

129. The pegRNA of claim 125 or 128, wherein the linker comprises the sequence TGAAATGA.

130. The pegRNA of claim 125, wherein the linker comprises a sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to, or comprising one, two, three, four, or five mutations relative to, the sequence TTACTAAA.

131. The pegRNA of claim 125 or 130, wherein the linker comprises the sequence TTACTAAA.

132. The pegRNA of any one of claims 109-131, wherein the pegRNA comprises the structure:5 '-[spacer] -[backbone scaffold] -[edit template] -[primer binding site] -[linker] -[structured motif] -3'.

133. The pegRNA of any one of claims 109-132, wherein the pegRNA comprises a sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to, or comprising one, two, three, four, or five mutations relative to, the sequence of SEQ ID NO: 1256.

134. The pegRNA of any one of claims 109-132, wherein the pegRNA comprises the sequence of SEQ ID NO: 1256.230 / 235B1195.70202WO00#14468377 v2135. The pegRNA of any one of claims 109-132, wherein the pegRNA comprises a sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to, or comprising one, two, three, four, or five mutations relative to, the sequence of SEQ ID NO: 1432.

136. The pegRNA of any one of claims 109-132, wherein the pegRNA comprises the sequence of SEQ ID NO: 1432.

137. The pegRNA of any one of claims 109-132, wherein the pegRNA comprises a sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to, or comprising one, two, three, four, or five mutations relative to, the sequence of SEQ ID NO: 1465.

138. The pegRNA of any one of claims 109-132, wherein the pegRNA comprises the sequence of SEQ ID NO: 1465.

139. A nicking guide RNA (ngRNA) comprising a spacer comprising a sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to, or comprising one, two, three, four, or five mutations relative to, the sequence of SEQ ID NO: 1257.

140. The ngRNA of claim 139, wherein the ngRNA comprises a spacer comprising the sequence of SEQ ID NO: 1257.

141. The ngRNA of claim 139 or 140, wherein the ngRNA comprises a backbone scaffold comprising a sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to, or comprising one, two, three, four, or five mutations relative to, the sequence of SEQ ID NO: 285.

142. The ngRNA of any one of claims 139-141, wherein the ngRNA comprises a backbone scaffold comprising the sequence of SEQ ID NO: 285.231 / 235B1195.70202WO00#14468377 v2143. The ngRNA of any one of claims 139-142, wherein the ngRNA comprises a sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to, or comprising one, two, three, four, or five mutations relative to, the sequence of SEQ ID NO: 1276.

144. The ngRNA of any one of claims 139-143, wherein the ngRNA comprises the sequence of SEQ ID NO: 1276.

145. A method comprising contacting a cell with a prime editor and the pegRNA of any one of claims 109-138.

146. The method of claim 145 further comprising providing a nicking guide RNA (ngRNA) of any one of claims 139-144.

147. The method of claim 145 or 146, wherein the cell is a retinal pigment epithelium (RPE) cell.

148. A cell produced by the method of any one of claims 145-146.

149. The cell of claims 148, wherein the cell is a human cell.

150. The cell of claim 148 or 149, wherein the cell is a retinal pigment epithelium (RPE) cell.

151. The cell of any one of claims 148-150, wherein the genome of the cell comprises a mutated A: T base pair at nucleotide position 68 in the RHO gene relative to a wild type RHO gene.

152. A method comprising contacting the cell of any one of claims 148-151 with a prime editor and the pegRNA of any one of claims 1-34.

153. A system comprising a pegRNA of SEQ ID NO: 1093, an ngRNA of SEQ ID NO: 1279, and a PE6g prime editor.232 / 235B1195.70202WO00#14468377 v2154. A system comprising a pegRNA pegRNA of SEQ ID NO: 889, an ngRNA of SEQ ID NO: 1279, and a PE6g prime editor.

155. A system comprising a pegRNA of SEQ ID NO: 1211, an ngRNA of SEQ ID NO: 1279, and a PE6g prime editor.

156. A system comprising a pegRNA of SEQ ID NO: 1432, an ngRNA of SEQ ID NO: 1279, and a PE6g prime editor.

157. A system comprising a pegRNA of SEQ ID NO: 1465, an ngRNA of SEQ ID NO: 1279, and a PE6g prime editor.

158. A method of prime editing a RHO gene comprising contacting a nucleic acid sequence encoding the RHO gene with a PE6g prime editor, a pegRNA of SEQ ID NO: 1093, and an ngRNA of SEQ ID NO: 1279.

159. A method of prime editing a RHO gene comprising contacting a nucleic acid sequence encoding the RHO gene with a PE6g prime editor, a pegRNA of SEQ ID NO: 889, and an ngRNA of SEQ ID NO: 1279.

160. A method of prime editing a RHO gene comprising contacting a nucleic acid sequence encoding the RHO gene with a PE6g prime editor, a pegRNA of SEQ ID NO: 1211, and an ngRNA of SEQ ID NO: 1279.

161. A method of prime editing a RHO gene comprising contacting a nucleic acid sequence encoding the RHO gene with a PE6g prime editor, a pegRNA of SEQ ID NO: 1432, and an ngRNA of SEQ ID NO: 1279.

162. A method of prime editing a RHO gene comprising contacting a nucleic acid sequence encoding the RHO gene with a PE6g prime editor, a pegRNA of SEQ ID NO: 1465, and an ngRNA of SEQ ID NO: 1279.233 / 235B1195.70202WO00#14468377 v2163. A lipid nanoparticle (LNP) comprising any of the pegRNAs, ngRNAs, systems, complexes, polynucleotides, vectors, or compositions of any of the preceding claims.

164. The LNP of claim 163, wherein the LNP comprises an ionizable lipid.

165. The LNP of claim 164, wherein the ionizable lipid is OF-02, lipid 5, lipid A9, or 306-O12B.

166. The LNP of any one of claims 163-165, wherein the LNP comprises a cationic lipid.

167. The LNP of claim 166, wherein the cationic lipid is Ql-SM-102, Qi-ALC-0315, DOTAP, DORI, or EPC.

168. The LNP of any one of claims 163-167, wherein the LNP comprises DOPE, cholesterol, and / or PEG.

169. The LNP of claim 168, wherein the LNP comprises C14-PEG.

170. The LNP of any one of claims 163-169, wherein the LNP comprises X% of an ionizable lipid, (60-X)% of a cationic lipid, approximately 10% DOPE, approximately 38.5% cholesterol, and approximately 1.5% C14-PEG, wherein X is any number between 0 and 60.234 / 235B1195.70202WO00#14468377 v2

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