Enzymes with ruvc domains

Description

ENZYMES WITH RUVC DOMAINS CROSS-REFERENCE

[0001] This application claims the benefit and priority of U.S. Provisional Patent Application No. 63 / 487,847, filed on March 1, 2023, which is incorporated herein by reference in its entirety for all purposes. SUMMARY

[0002] Modified nuclease systems comprising, in certain embodiments, are described in this document: a) a modified endonuclease comprising a sequence with at least 80% sequence identity with any of the following SEQ ID NOs: 1-5, 139-146, 303, 304, 6, 7-11, 12-14, 105-109, 110-116, and 117-138; and b) a modified guide polynucleotide configured to form a complex with the endonuclease and hybridize with a target nucleic acid sequence. In some embodiments, the endonuclease comprises a sequence with at least 90% sequence identity to any of the following SEQ ID NOs: 1-5, 139-146, 303, 304, 6, 7-11, 12-14, 105-109, 110-116, and 117-138. In some embodiments, the endonuclease comprises a sequence with 100% sequence identity to any of the following SEQ ID NOs: 1-5, 139-146, 303, 304, 6, 7-11, 12-14, 105-109, 110-116, and 117-138. In some embodiments, the modified guide polynucleotide comprises a crRNA and a tracrRNA.In some embodiments, the tracrRNA comprises a sequence with at least approximately 90% sequence identity with any of the following SEQ ID NOs: 215-222, 52, 147-151, 157-163, and 171-192. In some embodiments, the tracrRNA comprises a sequence with 100% sequence identity with any of the following SEQ ID NOs: 215-222, 52, 147-151, 157-163, and 171-192. Petition 870250090553, dated 03 / 10 / 2025, p. 5 / 262 2 / 251 one of the SEQ ID Nos: 215-222, 52, 147-151, 157-163, and 171192. In some embodiments, the modified guide polynucleotide is a single guide nucleic acid. In some embodiments, the modified guide polynucleotide is a double guide nucleic acid. In some embodiments, the modified guide polynucleotide is RNA. In some embodiments, the endonuclease is not a Cas9 endonuclease, a endonuclease Cas14, an endonuclease Cas12a, an endonuclease Cas12b, an endonuclease Cas12c, an endonuclease Cas12d, an endonuclease Cas12e, an endonuclease Cas13a, an endonuclease Cas13b, an endonuclease Cas13c, or an endonuclease Cas13d. In some In some embodiments, the endonuclease has less than 80% identity with a Cas9 endonuclease. In some embodiments, the endonuclease binds non-covalently to the modified guide polynucleotide. In some embodiments, the endonuclease is covalently bound to the modified guide polynucleotide.

[0003] Described in this document, in certain embodiments, the modified nuclease systems comprise: a) an endonuclease comprising a sequence with at least about 80% sequence identity with any of the SEQ ID NOs: 139-146 and 303; and b) a modified guide polynucleotide configured to form a complex with the endonuclease and hybridize with a target nucleic acid sequence, the manipulated guide polynucleotide comprising a sequence with at least 80% sequence identity with any of the SEQ ID NOs: 215-222.

[0004] Described in this document, in certain embodiments, modified nuclease systems comprise: Petition 870250090553, dated 03 / 10 / 2025, page 6 / 262 3 / 251 a) an endonuclease comprising a sequence with at least about 80% sequence identity with any of the SEQ ID NOs: 7-11; and b) a modified guide polynucleotide configured to form a complex with the endonuclease and hybridize with a target nucleic acid sequence, the manipulated guide polynucleotide comprising a sequence with at least 80% sequence identity with SEQ ID NO: 52.

[0005] Described in this document, in certain embodiments, the modified nuclease systems comprise: a) an endonuclease comprising a sequence with at least about 80% sequence identity with any of the SEQ ID NOs: 105-109; and b) a modified guide polynucleotide configured to form a complex with the endonuclease and hybridize with a target nucleic acid sequence, the manipulated guide polynucleotide comprising a sequence with at least 80% sequence identity with any of the SEQ ID NOs: 147-151.

[0006] Described in this document, in certain embodiments, the modified nuclease systems comprise: a) an endonuclease comprising a sequence with at least about 80% sequence identity with any of the SEQ ID NOs: 110-116; and b) a modified guide polynucleotide configured to form a complex with the endonuclease and hybridize with a target nucleic acid sequence, the manipulated guide polynucleotide comprising a sequence with at least 80% sequence identity with any of the SEQ ID NOs: 157-163.

[0007] Described in this document, in certain embodiments, modified nuclease systems comprise: Petition 870250090553, dated 03 / 10 / 2025, page 7 / 262 4 / 251 a) an endonuclease comprising a sequence with at least about 80% sequence identity with any of the SEQ ID NOs: 117-138; and b) a modified guide polynucleotide configured to form a complex with the endonuclease and hybridize with a target nucleic acid sequence, the manipulated guide polynucleotide comprising a sequence with at least 80% sequence identity with any of the SEQ ID NOs: 171-192.

[0008] In some embodiments, the modified guide polynucleotide is a single guide nucleic acid.

[0009] In some embodiments, the modified guide polynucleotide is a double guide nucleic acid.

[0010] In some embodiments, the modified guide polynucleotide is RNA.

[0011] In some embodiments, the endonuclease is not a Cas9 endonuclease, a Cas14 endonuclease, a endonuclease Cas12a, an endonuclease Cas12b, an endonuclease Cas12c, an endonuclease Cas12d, an endonuclease Cas12e, an endonuclease Cas13a, an endonuclease Cas13b, an endonuclease Cas13c or a Cas13d endonuclease.

[0012] In some embodiments, the endonuclease has less than 80% identity with a Cas9 endonuclease.

[0013] In some embodiments, the endonuclease binds non-covalently to the modified guide polynucleotide.

[0014] In some embodiments, the endonuclease is covalently linked to the modified guide polynucleotide.

[0015] In some embodiments, the endonuclease is fused to the modified guide polynucleotide. Petition 870250090553, dated 03 / 10 / 2025, page 8 / 262 5 / 251

[0016] In certain embodiments, methods for modifying a target nucleic acid sequence are described in this document, comprising contacting the target nucleic acid sequence using the modified nuclease system described in this document. In some embodiments, modifying the target nucleic acid sequence comprises ligating, cutting, or cleaving the target nucleic acid sequence. In some embodiments, the target nucleic acid sequence comprises genomic DNA, viral DNA, viral RNA, or bacterial DNA. In some embodiments, the modification is in vitro. In some embodiments, the modification is in vivo. In some embodiments, the modification is ex vivo. In some embodiments, the gRNA comprises a sequence with any of the SEQ ID NOs: 251-260, 271-274, and 279-290. In some embodiments, the target nucleic acid sequence comprises a sequence with any of the SEQ ID NOs: 261-270, 275-278, and 291-302.

[0017] In this document, methods for modifying a target nucleic acid sequence in a mammalian cell are described in certain embodiments, comprising contacting the mammalian cell using the modified nuclease system described in this document. In some embodiments, the methods further comprise selecting cells that comprise the modification.

[0018] Methods for modifying HAO1 are described in certain embodiments in this document, comprising bringing HAO1 into contact using a modified nuclease system comprising: a) an endonuclease comprising a sequence with at least about 80% sequence identity with any of the SEQ ID NOs: 139-146 and 303; and b) a modified guide polynucleotide configured for Petition 870250090553, dated 03 / 10 / 2025, page 9 / 262 6 / 251 form a complex with the endonuclease and hybridize with a target nucleic acid sequence, the manipulated guide polynucleotide comprising a sequence with at least 80% sequence identity with any of the SEQ ID NOs: 215-222. In some embodiments, the modified guide polynucleotide comprises a sequence from any of the SEQ ID NOs: 251-260. In some embodiments, the target nucleic acid sequence comprises a sequence from any of the SEQ ID NOs: 261-270.

[0019] In certain embodiments, methods for modifying HAO1 are described in this document, comprising bringing HAO1 into contact using a modified nuclease system comprising: a) an endonuclease comprising a sequence with at least about 80% sequence identity with SEQ ID NO: 304; and b) a modified guide polynucleotide configured to form a complex with the endonuclease and hybridize with a target nucleic acid sequence. In some embodiments, the modified guide polynucleotide comprises a sequence from any of the SEQ ID NOs: 271-274. In some embodiments, the target nucleic acid sequence comprises a sequence from any of the SEQ ID NOs: 275-278.

[0020] Methods for modifying TTR are described in certain embodiments in this document, comprising bringing the TTR into contact using a modified nuclease system comprising: a) an endonuclease comprising a sequence with at least about 80% sequence identity with any of the SEQ ID NOs: 139-146 and 303; and b) a modified guide polynucleotide configured to form a complex with the endonuclease and hybridize with a Petition 870250090553, dated 03 / 10 / 2025, p. 10 / 262 7 / 251 target nucleic acid sequence, the manipulated guide polynucleotide comprising a sequence with at least 80% sequence identity with any of the SEQ ID NOs: 215-222. In some embodiments, the modified guide polynucleotide comprises a sequence from any of the SEQ ID NOs: 279-290. In some embodiments, the target nucleic acid sequence comprises a sequence from any of the SEQ ID NOs: 291-302.

[0021] In certain embodiments, cells comprising the modified nuclease system described in this document are described herein. In some embodiments, the cell is a eukaryotic cell. In some embodiments, the cell is a mammalian cell. In some embodiments, the cell is an immortalized cell. In some embodiments, the cell is an insect cell. In some embodiments, the cell is a yeast cell. In some embodiments, the cell is a plant cell. In some embodiments, the cell is a fungal cell. In some embodiments, the cell is a prokaryotic cell. In some embodiments, the cell is A549, HEK-293, HEK-293T, BHK, CHO, HeLa, MRC5, Sf9, Cos-1, Cos-7, Vero, BSC 1, BSC 40, BMT 10, WI38, HeLa, Saos, C2C12, L cell, HT1080, HepG2, Huh7, K562, a primary cell or a derivative thereof. In some embodiments, the cell is a modified cell. In some embodiments, the cell is a stable cell.

[0022] Additional aspects and advantages of the present disclosure will become readily apparent to those skilled in the art from the detailed description that follows, in which only illustrative embodiments of the present disclosure are shown and described. As will be perceived, Petition 870250090553, dated 03 / 10 / 2025, p. 11 / 262 8 / 251 The present disclosure is subject to other different forms, and its various details are subject to modifications in several obvious aspects, all without departing from the disclosure. Consequently, the figures and description should be considered illustrative in nature and not restrictive. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] The new disclosure features are set out in particular in the appended claims. A better understanding of the features and advantages of this disclosure will be obtained by reference to the following detailed description which sets out illustrative embodiments in which the disclosure principles are used, and the appended figures (also Figure and FIG. in this document), of which:

[0024] FIG. 1A represents a SeqLogo of the protospacer adjacent motif (PAM) recognized by MG171-1. FIG. 1B represents the 5 nt cleavage position of the PAM obtained from the in vitro cleavage assay and NGS sequencing.

[0025] FIG. 2 represents the analysis of the results of gene editing at the DNA level for editing human HAO1 by MG21-1 in Hep3B cells.

[0026] FIG. 3 represents the analysis of the results of gene editing at the DNA level for editing human TTR by MG21-1 in Hep3B cells.

[0027] FIG. 4 represents the analysis of the results of gene editing at the DNA level for editing human HAO1 by MG23-1 in Hep3B cells. BRIEF DESCRIPTION OF THE SEQUENCE LISTING

[0028] The Sequence Listing archived here Petition 870250090553, dated 03 / 10 / 2025, page 12 / 262 9 / 251 provides examples of polynucleotide and polypeptide sequences for use in methods, compositions, and systems as disclosed. Below are illustrative descriptions of sequences therein. MG2

[0029] The SEQ ID Nos: 15-16 show the peptide sequences of PAM interaction domains of MG2 nucleases.

[0030] The SEQ ID Nos: 53-66 show the nucleotide sequences of MG2 nuclease target sites. MG4

[0031] The SEQ ID Nos: 17-22 show the peptide sequences of PAM interaction domains of MG4 nucleases.

[0032] SEQ IDs 67-76 show the nucleotide sequences of MG4 nuclease target sites. MG5

[0033] The SEQ ID NOs: 1-5 show the complete peptide sequences of the MG5 nucleases.

[0034] SEQ IDs 23-27 show the peptide sequences of PAM interaction domains of MG5 nucleases. MG6

[0035] SEQ IDs 28-36 show the peptide sequences of PAM interaction domains of MG6 nucleases.

[0036] The SEQ ID Nos: 77-86 show the nucleotide sequences of MG6 nuclease target sites. MG7

[0037] SEQ ID NO: 51 shows the sequence Petition 870250090553, dated 03 / 10 / 2025, page 13 / 262 10 / 251 nucleotide of a tracrRNA MG7 derived from the same loci as an MG7 nuclease.

[0038] SEQ ID NO: 37 shows the peptide sequence of the PAM interaction domain of nuclease MG7.

[0039] The SEQ ID Nos: 87-95 show the nucleotide sequences of MG7 nuclease target sites. MG16

[0040] SEQ ID NO: 38 shows the peptide sequence of the PAM interaction domain of nuclease MG16.

[0041] The SEQ ID Nos: 96-104 show the nucleotide sequences of MG16 nuclease target sites. MG21

[0042] SEQ IDs 139-146 and 303 show the complete peptide sequences of MG21 nucleases.

[0043] SEQ IDs 215-222 show the nucleotide sequences of MG21 tracrRNAs derived from the same loci as MG21 nucleases.

[0044] The SEQ ID Nos: 223-230 show the nucleotide sequences of CRISPR MG21 repeats. MG23

[0045] SEQ ID NO: 304 shows the complete peptide sequence of an MG23 nuclease. MG4 9

[0046] SEQ ID NO: 39 shows the peptide sequence of PAM interaction domains of an MG49 nuclease. MG86

[0047] SEQ ID NO: 6 shows the complete peptide sequence of an MG86 nuclease.

[0048] SEQ ID NO: 40 shows the peptide sequence of PAM interaction domains of an MG86 nuclease. Petition 870250090553, dated 03 / 10 / 2025, page 14 / 262 11 / 251 MG112

[0049] SEQ IDs 7-11 show the complete peptide sequences of the MG112 nucleases.

[0050] SEQ IDs 41-45 show the peptide sequences of PAM interaction domains of MG112 nucleases.

[0051] nnRTCY is the nucleotide sequence of a PAM of an MG112 nuclease.

[0052] SEQ ID NO: 50 shows the nucleotide sequence of an sgRNA modified to function with an MG112 nuclease.

[0053] SEQ ID NO: 52 shows the nucleotide sequence of an MG7 tracrRNA derived from the same loci as the MG112 nucleases above. MG116

[0054] The SEQ ID Nos: 12-14 show the complete peptide sequences of the MG116 nucleases.

[0055] The SEQ ID Nos: 46-48 show the peptide sequences of PAM interaction domains of MG116 nucleases. MG171

[0056] The SEQ ID Nos: 105-109 show the complete peptide sequences of the MG171 nucleases.

[0057] The SEQ ID Nos: 147-151 show the nucleotide sequences of MG171 tracrRNAs derived from the same loci as the MG171 nucleases.

[0058] The SEQ ID Nos: 152-156 show the nucleotide sequences of CRISPR MG171 repeats.

[0059] SEQ IDs 231-240 show the nucleotide sequences of sgRNAs modified to function with a Petition 870250090553, dated 03 / 10 / 2025, page 15 / 262 12 / 251 nuclease MG171. MG177

[0060] The SEQ ID Nos: 110-116 show the complete peptide sequences of the MG177 nucleases.

[0061] The SEQ ID Nos: 157-163 show the nucleotide sequences of MG177 tracrRNAs derived from the same loci as the MG177 nucleases.

[0062] The SEQ ID Nos: 164-170 show the nucleotide sequences of CRISPR repeats MG177.

[0063] The SEQ ID Nos: 241-250 show the nucleotide sequences of sgRNAs modified to function with an MG171 nuclease. MG183

[0064] SEQ IDs 117-138 show the complete peptide sequences of the MG183 nucleases.

[0065] SEQ IDs 171-192 show the nucleotide sequences of MG183 tracrRNAs derived from the same loci as MG183 nucleases.

[0066] The SEQ ID Nos: 193-214 show the nucleotide sequences of CRISPR MG183 repeats. HAO1 targeting with MG21-1

[0067] SEQ IDs 251-260 show the nucleotide sequences of sgRNAs modified to function with an MG21-1 nuclease to target human HAO1.

[0068] SEQ IDs 261-270 show the DNA sequences of human HAO1 target sites. HAO1 targeting with MG23-1

[0069] SEQ IDs 271-274 show the nucleotide sequences of sgRNAs modified to function with an MG31-1 nuclease to target human HAO1. Petition 870250090553, dated 03 / 10 / 2025, page 16 / 262 13 / 251

[0070] SEQ IDs 275-278 show the DNA sequences of human HAO1 target sites. TTR steering with MG21-1

[0071] SEQ IDs 279-290 show the nucleotide sequences of sgRNAs modified to function with an MG21-1 nuclease to target human TTR.

[0072] SEQ IDs 291-302 show the DNA sequences of human TTR target sites. DETAILED DESCRIPTION

[0073] Although various embodiments of disclosure have been shown and described in this document, it will be obvious to those skilled in the art that such embodiments are provided only as examples. Numerous variations, alterations, and substitutions may occur to those skilled in the art without departing from the disclosure. It should be understood that various alternatives to the embodiments of disclosure described in this document may be employed.

[0074] Whenever the term at least, greater than, or greater than or equal to precedes the first numerical value in a series of two or more numerical values, the term at least, greater than, or greater than or equal to applies to each of the numerical values ​​in that series of numerical values. For example, greater than or equal to 1, 2, or 3 is equivalent to greater than or equal to 1, greater than or equal to 2, or greater than or equal to 3.

[0075] Whenever the term not more than, less than, or less than or equal to precedes the first numerical value in a series of two or more numerical values, the term not more than, less than, or less than or equal to applies to each of the values. Petition 870250090553, dated 03 / 10 / 2025, p. 17 / 262 14 / 251 numerical values ​​in this series of numerical values. For example, less than or equal to 3, 2, or 1 is equivalent to less than or equal to 3, less than or equal to 2, or less than or equal to 1.

[0076] The practice of some methods disclosed in this document employs, unless otherwise indicated, techniques from immunology, biochemistry, chemistry, molecular biology, microbiology, cell biology, genomics, and recombinant DNA.

[0077] As used in this document, the singular forms a, an, some, and any should also include the plural forms, unless the context clearly indicates otherwise. Furthermore, to the extent that the terms including, includes, having, has, with, or variants thereof are used in the detailed description and / or claims, such terms are intended to be inclusive in a manner similar to the term comprising.

[0078] The term about or approximately means within an acceptable error range for the specific value, as determined by one skilled in the art, which will depend in part on how the value is measured or determined, i.e., the limitations of the measurement system. For example, about may mean within one or more standard deviations, according to practice in the art. Alternatively, about may mean a range of up to 20%, up to 15%, up to 10%, up to 5%, or up to 1% of a given value.

[0079] The term nucleotide, as used in this document, refers to a base-sugar-phosphate combination. The nucleotides considered include naturally occurring nucleotides and synthetic nucleotides. The Petition 870250090553, dated 03 / 10 / 2025, page 18 / 262 15 / 251 Nucleotides can be monomeric units of a nucleic acid sequence (e.g., deoxyribonucleic acid (DNA) and ribonucleic acid (RNA)). The term nucleotide includes ribonucleoside triphosphates adenosine triphosphate (ATP), uridine triphosphate (UTP), cytosine triphosphate (CTP), guanosine triphosphate (GTP), and deoxyribonucleoside triphosphates such as dATP, dCTP, dITP, dUTP, dGTP, dTTP, or derivatives thereof. Such derivatives include, for example, [aS]dATP, 7-deaza-dGTP, and 7-deaza-dATP, and nucleotide derivatives that confer nuclease resistance in the nucleic acid molecule that contains them. The term nucleotide, as used in this document, encompasses dideoxyribonucleoside triphosphates (ddNTPs) and derivatives thereof. Illustrative examples of ddNTPs include, but are not limited to, ddATP, ddCTP, ddGTP, ddITP, and ddTTP.A nucleotide can be detectably labeled or unlabeled, such as by using fractions comprising optically detectable fractions (e.g., fluorophores) or quantum dots. Detectable markers include, for example, radioactive isotopes, fluorescent markers, chemiluminescent markers, bioluminescent markers, and enzymatic markers. Fluorescent nucleotide markers include, but are not limited to, fluorescein, 5-carboxyfluorescein (FAM), 2',7'-dimethoxy-4',5-dichloro-6-carboxyfluorescein (JOE), rhodamine, 6-carboxyroidamine (R6G), N,N,N',N'-tetramethyl-6-carboxyrodamine (TAMRA), 6-carboxy-X-rhodamine (ROX), 4-(4'-dimethylaminophenylazo)benzoic acid (DABCYL), cascade blue, Oregon green, Texas red, cyanine, and 5-(2'-aminoethyl)aminonaphthalene-1-sulfonic acid (EDANS). Specific examples of nucleotides. Petition 870250090553, dated 03 / 10 / 2025, page 19 / 262 16 / 251 fluorescently labeled compounds include [R6G]dUTP, [TAMRA]dUTP, [R110]dCTP, [R6G]dCTP, [TAMRA]dCTP, [JOE]ddATP, [R6G]ddATP, [FAM]ddCTP, [R110]ddCTP, [TAMRA]ddGTP, [ROX]ddTTP, [dR6G]ddATP, [dR110]ddCTP, [dTAMRA]ddGTP and [dROX]ddTTP, available from Perkin Elmer, Foster City, Calif; FluoroLink Deoxynucleotides, FluoroLink Cy3-dCTP, FluoroLink Cy5-dCTP, FluoroLink Fluor X-dCTP, FluoroLink Cy3-dUTP, and FluoroLink Cy5-dUTP, available from Amersham, Arlington Heights, IL.; Fluorescein-15-dATP, Fluorescein12-dUTP, Tetramethylrhodamine-6-dUTP, IR770-9-dATP, Fluorescein-12-ddUTP, Fluorescein-12-UTP and Fluorescein-15-2'-dATP, available from Boehringer Mannheim, Indianapolis, Ind.; and chromosome-labeled nucleotides, BODIPY-FL-14-UTP, BODIPY-FL-4-UTP, BODIPY-TMR-14-UTP, BODIPY-TMR-14-dUTP, BODIPY-TR-14-UTP, BODIPY-TR-14-dUTP, Cascade Blue-7-UTP, Cascade Blue-7-dUTP, fluorescein-12UTP, fluorescein-12-dUTP, Oregon Green 488-5-dUTP, Rhodamine Green-5-UTP, Rhodamine Green-5-dUTP, tetramethylrhodamine-6-UTP, tetramethylrhodamine-6-dUTP, Texas Red-5-UTP, Texas Red-5-dUTP, and Texas Red-12-dUTP, available from Molecular Probes, Eugene, Oregon. The term nucleotide encompasses chemically modified nucleotides. An example of a chemically modified nucleotide is biotin-dNTP. Non-limiting examples of biotinylated dNTPs include biotin-dATP (e.g., bio-N6-ddATP, biotin-14dATP), biotin-dCTP (e.g., biotin-11-dCTP, biotin-14-dCTP), and biotin-dUTP (e.g., biotin-11-dUTP, biotin-16-dUTP, biotin-20-dUTP).

[0080] The terms polynucleotide, oligonucleotide and nucleic acid are used Petition 870250090553, dated 03 / 10 / 2025, page 20 / 262 17 / 251 indistinctly to refer to a polymeric form of nucleotides of any length, whether deoxyribonucleotides or ribonucleotides, or their analogues, whether in single, double or multiple stranded form. The polynucleotides contemplated include a gene or fragment thereof. Exemplary polynucleotides include, but are not limited to, DNA, RNA, coding or non-coding regions of a gene or gene fragment, loci defined from linkage analysis, exons, introns, messenger RNA (mRNA), transfer RNA (tRNA), ribosomal RNA (rRNA), short interfering RNA (siRNA), Short hairpin RNA (shRNA), microRNA (miRNA), ribozymes, cDNA, recombinant polynucleotides, branched polynucleotides, plasmids, vectors, cell-free polynucleotides, including cell-free DNA (cfDNA) and cell-free RNA (cfRNA), nucleic acid probes, and primers. In a polynucleotide, when referring to a T, a T means U (Uracil) in RNA and T (Thymine) in DNA. A polynucleotide can be exogenous or endogenous to a cell and / or exist in a cell-free environment. The term polynucleotide encompasses modified polynucleotides (e.g., altered backbone, sugar, or nucleobase). If present, modifications to the nucleotide structure are conferred before or after polymer assembly. Non-limiting examples of modifications include: 5-bromouracil, peptide nucleic acid, xene nucleic acid, morpholinos, blocked nucleic acids, glycol nucleic acids, threose nucleic acids, dideoxynucleotides, cordycepin, 7-deaza-GTP, fluorophores (e.g., rhodamine or fluorescein linked to sugar), thiol-containing nucleotides, linked nucleotides Petition 870250090553, dated 03 / 10 / 2025, page 21 / 262 18 / 251 to biotin, fluorescent base analogs, CpG islands, methyl-7-guanosine, methylated nucleotides, inosine, thiouridine, pseudouridine, dihydrouridine, keuosine, and wyosine. The nucleotide sequence may be interrupted by non-nucleotide components.

[0081] The terms peptide, polypeptide, and protein are used interchangeably in this document to refer to a polymer of at least two amino acid residues linked by peptide bonds. This term does not represent a specific polymer length, nor is it intended to imply or distinguish whether the peptide is produced using recombinant techniques, chemical or enzymatic synthesis, or is occurring naturally. The terms apply to naturally occurring amino acid polymers as well as to amino acid polymers comprising at least one modified amino acid. In some embodiments, the polymer is interrupted by non-amino acids. The terms include amino acid chains of any length, including complete proteins and proteins with or without secondary or tertiary structure (e.g., domains).The terms also encompass an amino acid polymer that has been modified, for example, by disulfide bond formation, glycosylation, lipidation, acetylation, phosphorylation, oxidation, and any other manipulation, such as conjugation with a labeling component. The terms amino acid and amino acids, as used in this document, refer to natural and non-natural amino acids, including, but not limited to, modified amino acids. Modified amino acids include amino acids that have been chemically modified to include a chemical group or fraction. Petition 870250090553, dated 03 / 10 / 2025, p. 22 / 262 19 / 251 which is not naturally present in the amino acid. The term amino acid includes both D-amino acids and L-amino acids.

[0082] As used in this document, operationally linked, operable linkage, operatively linked, or grammatical equivalents thereof refer to an arrangement of genetic elements, for example, a promoter, an enhancer, a polyadenylation sequence, etc., in which an operation (e.g., movement or activation) of a first genetic element has some effect on the second genetic element. The effect on the second genetic element may be, but not necessarily, of the same type as the operation on the first genetic element. For example, two genetic elements are operationally linked if the movement of the first element causes an activation of the second element. For example, a regulatory element, which may comprise promoter and / or enhancer sequences, is operationally linked to a coding region if the regulatory element helps to initiate transcription of the coding sequence.There may be intervening residues between the regulatory element and the encoding region, as long as this functional relationship is maintained.

[0083] A “functional fragment” of a DNA or protein sequence refers to a fragment that retains a biological activity (functional or structural) that is substantially similar to a biological activity of the complete DNA or protein sequence. A biological activity of a DNA sequence includes its ability to influence expression in a manner attributed to the full-length sequence. Petition 870250090553, dated 03 / 10 / 2025, p. 23 / 262 20 / 251

[0084] The terms modified, synthetic, and artificial are used interchangeably in this document to refer to an object that has been modified by human intervention. For example, the terms may refer to a polynucleotide or polypeptide that does not occur naturally. A modified peptide has, but does not require, low sequence identity (e.g., less than 50% sequence identity, less than 25% sequence identity, less than 10% sequence identity, less than 5% sequence identity, less than 1% sequence identity) to a naturally occurring human protein. For example, the VPR and VP64 domains are synthetic transactivation domains.Non-limiting examples include the following: a nucleic acid may be modified by altering its sequence to a sequence that does not occur in nature; a nucleic acid modified by its binding to a nucleic acid with which it does not associate in nature, so that the bound product possesses a function not present in the original nucleic acid; a modified nucleic acid synthesized in vitro with a sequence that does not exist in nature; a protein modified by altering its amino acid sequence to a sequence that does not exist in nature; a modified protein that acquires a new function or property. A modified system comprises at least one modified component.

[0085] The term “tracrRNA” or “tracr sequence” means transactivating CRISPR RNA. tracrRNA interacts with CRISPR RNA (cr) to form a guide nucleic acid (e.g., guide RNA or gRNA) that can hybridize with a target nucleic acid and thereby direct a nuclease associated with the target nucleic acid. Petition 870250090553, dated 03 / 10 / 2025, p. 24 / 262 21 / 251

[0086] As used in this document, a guide nucleic acid or “guide polynucleotide” refers to a nucleic acid that can hybridize with a target nucleic acid and thereby directs an associated nuclease to the target nucleic acid. A guide nucleic acid is, but is not limited to, RNA (guide RNA or gRNA), DNA, or a mixture of RNA and DNA. A guide nucleic acid may include a crRNA or a tracrRNA or a combination of both. The term guide nucleic acid encompasses both a modified guide nucleic acid and a guide nucleic acid programmable to bind specifically to the target nucleic acid. A portion of the target nucleic acid may be complementary to a portion of the guide nucleic acid. The strand of a double-stranded target polynucleotide that is complementary to and hybridizes with the guide nucleic acid is the complementary strand. The strand of the double-stranded target polynucleotide that is complementary to the complementary strand and therefore not complementary to the guide nucleic acid is called the non-complementary strand.A guide nucleic acid with one polynucleotide chain is a “single guide nucleic acid.” A guide nucleic acid with two polynucleotide chains is a “double guide nucleic acid.” Unless otherwise specified, the term guide nucleic acid is inclusive, referring to both single and double guide nucleic acids. A guide nucleic acid may comprise a segment referred to as a “nucleic acid targeting segment” or a “nucleic acid targeting sequence,” or a “spacer.” A nucleic acid targeting segment may include a subsegment referred to as a protein-binding segment or protein-binding sequence. Petition 870250090553, dated 03 / 10 / 2025, p. 25 / 262 22 / 251 Cas protein binding segment.

[0087] As used in this document, the term complex refers to a union of at least two components. The two components may retain the properties / activities they had before the formation of the complex or gain properties as a result of the formation of the complex. The joining includes, but is not limited to, covalent bonding, non-covalent bonding (i.e., hydrogen bonding, ionic interactions, Van der Waals interactions, and hydrophobic bonding), use of a ligand, fusion, or any other suitable method. The components of a contemplated complex include polynucleotides, polypeptides, or combinations thereof. For example, a complex comprises an endonuclease and a guide polynucleotide.

[0088] The term “sequence identity” or “percent identity,” in the context of two or more nucleic acids or polypeptide sequences, refers to two (e.g., in a pairwise alignment) or more (e.g., in a multi-sequence alignment) sequences that are the same or have a specified percentage of amino acid or nucleotide residues that are the same when compared and aligned for maximum match in a local or global comparison window, as measured using a sequence comparison algorithm. Suitable sequence comparison algorithms for polypeptide sequences include, for example, BLASTP using parameters of a word length (W) of 3, an expectation (E) of 10, and the BLOSUM62 scoring matrix establishing gap costs in existence of 11, extent of 1, and using a composition scoring matrix adjustment. Petition 870250090553, dated 03 / 10 / 2025, page 26 / 262 23 / 251 conditional for polypeptide sequences with more than 30 residues; BLASTP using parameters of a word length (W) of 2, an expectation (E) of 1000000 and the PAM30 scoring matrix setting gap costs at 9 to open gaps and 1 to extend gaps to sequences of less than 30 residues (these are the default parameters for BLASTP in the BLAST package, available at https: / / blast.ncbi.nlm.nih.gov); CLUSTALW with parameters of the Smith-Waterman homology search algorithm with parameters of a match of 2, a mismatch of -1 and a gap of -1; MUSCLE with default parameters; MAFFT with retree parameters of 2 and maxiterations of 1000; Novafold with default parameters.

[0089] Included in the present disclosure are variants of any of the enzymes described in this document with one or more conservative amino acid substitutions. Such conservative substitutions can be made in the amino acid sequence of a polypeptide without disrupting the three-dimensional structure or function of the polypeptide. Conservative substitutions can be achieved by replacing amino acids with similar hydrophobicity, polarity, and R-chain length. Additionally or alternatively, when comparing aligned sequences of homologous proteins from different species, conservative substitutions can be identified by locating amino acid residues that have been mutated between species (e.g., non-conserved residues) without altering the basic functions of the encoded proteins. Such conservatively substituted variants may include variants with at least about 20%, at least Petition 870250090553, dated 03 / 10 / 2025, p. 27 / 262 24 / 251 less about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99% identity of any of the endonuclease protein sequences described in this document (e.g., MG2 family endonucleases, MG4, MG5, MG6, MG7, MG16, MG21, MG23, MG49, MG86, MG112, MG116, MG171, MG177, or MG183 described in this document). In some embodiments, such conservatively substituted variants are functional variants.Such functional variants may include sequences with substitutions such that the activity of critical residues in the endonuclease active site is not interrupted. In some embodiments, a functional variant of any of the proteins described in this document lacks substitution of at least one of the residues predicted to be essential. In some embodiments, a functional variant of any of the proteins described in this document lacks substitution of all residues predicted to be essential.

[0090] Conservative substitution tables that provide functionally similar amino acids are available in a variety of references (see, for example, Creighton, Proteins: Structures and Molecular Properties (W.H. Freeman & Co.; 2nd edition (December 1993)). Petition 870250090553, dated 03 / 10 / 2025, p. 28 / 262 25 / 251 The following eight groups each contain amino acids that are conservatively substituted for one another: 1) Alanine (A), Glycine (G); 2) Aspartic acid (D), glutamic acid (E); 3) Asparagine (N), glutamine (Q); 4) Arginine (R), lysine (K); 5) Isoleucine (I), leucine (L), methionine (M), valine (V); 6) Phenylalanine (F), tyrosine (Y), tryptophan (W); 7) Serine (S), threonine (T); and 8) Cysteine ​​(C), methionine (M) Overview

[0091] The discovery of novel Cas enzymes with unique functionality and structure may offer the potential to further disrupt deoxyribonucleic acid (DNA) editing technologies, improving speed, specificity, functionality, and ease of use. Given the predicted prevalence of clustered regularly interspaced short palindromic repeat (CRISPR) systems in microbes and the sheer diversity of microbial species, relatively few functionally characterized CRISPR / Cas enzymes exist in the literature. This is partly because a large number of microbial species may not be easily cultured under laboratory conditions. Metagenomic sequencing of natural environmental niches representing a large number of microbial species may offer the potential to dramatically increase the number of known novel CRISPR / Cas systems and accelerate the discovery of new functionalities. Petition 870250090553, dated 03 / 10 / 2025, page 29 / 262 26 / 251 of oligonucleotide editing. A recent example of the fruitfulness of such an approach is demonstrated by the discovery, in 2016, of the CRISPR CasX / CasY systems from metagenomic analysis of natural microbial communities.

[0092] Cas / CRISPR systems are RNA-targeted nuclease complexes that have been described to function as an adaptive immune system in microbes. In their natural context, CRISPR / Cas systems occur in CRISPR operons or loci (clustered regularly interspaced short palindromic repeats), which generally comprise two parts: (i) an array of short repetitive sequences (30-40 bp) separated by equally short spacer sequences, which encode the RNA-based targeting element; and (ii) ORFs that encode the Cas nuclease polypeptide directed by the RNA-based targeting element along with accessory proteins / enzymes.Efficient targeting of a particular nucleic acid sequence to a nuclease generally requires both (i) complementary hybridization between the first 6-8 nucleic acids of the target (the target seed) and the guide crRNA; and (ii) the presence of a protospacer adjacent motif (PAM) sequence within a defined proximity of the target seed (the PAM usually being a sequence not commonly represented within the host genome). Depending on the exact function and organization of the system, CRISPR-Cas systems are commonly organized into 2 classes, 5 types, and 16 subtypes based on shared functional characteristics and evolutionary similarity.

[0093] Class 1 CRISPR-Cas systems have Petition 870250090553, dated 03 / 10 / 2025, page 30 / 262 27 / 251 large multi-subunit effector complexes and comprise Types I, III and IV.

[0094] Type I CRISPR-Cas systems are considered to be of moderate complexity in terms of components. In Type I CRISPR-Cas systems, the RNA targeting element array is transcribed as a long precursor crRNA (pre-crRNA) that is processed into repeat elements to release short, mature crRNAs that target the nuclease complex to nucleic acid targets when they are followed by a suitable short consensus sequence, called the protospacer adjacent motif (PAM). This processing occurs via an endoribonuclease subunit (Cas6) of a large endonuclease complex called Cascade, which also comprises a protein nuclease component (Cas3) of the crRNA-targeted nuclease complex. Cas 1 nucleases function primarily as DNA nucleases.

[0095] Type III CRISPR systems can be characterized by the presence of a central nuclease, known as Cas10, along with a mysterious repeat-associated protein (RAMP) comprising Csm or Cmr protein subunits. As in type I systems, mature crRNA is processed from a pre-crRNA using a Cas6-like enzyme. Unlike type I and II systems, type III systems appear to target and cleave DNA-RNA duplexes (such as DNA strands being used as templates for an RNA polymerase).

[0096] Type IV CRISPR-Cas systems have an effector complex consisting of a highly reduced large subunit nuclease (csf1), two genes for proteins Petition 870250090553, dated 03 / 10 / 2025, page 31 / 262 28 / 251 RAMP systems for Cas5 (csf3) and Cas7 (csf2) groups, and in some cases, a gene for a predicted small subunit; these systems are commonly found in endogenous plasmids.

[0097] Class II CRISPR-Cas systems generally have single polypeptide multidomain nuclease effectors and comprise Types II, V, and VI.

[0098] Type II CRISPR-Cas systems are considered the simplest in terms of components. In Type II CRISPR-Cas systems, processing the CRISPR array into mature crRNAs does not require the presence of a special endonuclease subunit, but rather a small transcoded crRNA (tracrRNA) with a region complementary to the repeat sequence of the array; the tracrRNA interacts with its corresponding effector nuclease (Cas9) and the repeat sequence to form a precursor dsRNA structure, which is cleaved by endogenous RNase III to generate a mature Cas9 enzyme loaded with tracrRNA and crRNA. Cas II nucleases are known as DNA nucleases. The Cas9 effector has a characteristic structure consisting of a RuvC-like endonuclease domain that adopts the RNase H fold with an unrelated HNH nuclease domain inserted into the folds of the RuvC-like nuclease domain.The RuvC-like domain is responsible for cleaving the target DNA strand (e.g., complementary crRNA), while the HNH domain is responsible for cleaving the displaced DNA strand.

[0099] Type V CRISPR-Cas systems are characterized by a nuclease effector structure (Cas12) similar to that of Type II / Cas9, comprising a RuvC-like domain. Similar to Type II, most (but not all) Type V CRISPR systems use a Petition 870250090553, dated 03 / 10 / 2025, p. 32 / 262 29 / 251 tracrRNA to process pre-crRNAs into mature crRNAs; however, unlike Type II systems that require RNase III to cleave the pre-crRNA into multiple crRNAs, Type V systems are capable of using the effector nuclease itself (Cas12) to cleave pre-crRNAs. Like Type II CRISPR-Cas systems, Type V CRISPR-Cas systems are again known as DNA nucleases. Unlike Type II CRISPR-Cas systems, some Type V enzymes (e.g., Cas12a) appear to have robust single-strand nonspecific deoxyribonuclease activity that is activated by the first crRNA-directed cleavage of a double-stranded target sequence.

[0100] Type VI CRISPR-Cas systems are unique because they appear to be the only class so far known of RNA-guided RNA endonucleases. Instead of RuvC-like domains, the single polypeptide effector of Type VI systems (Cas13) comprises two HEPN ribonuclease domains. Unlike both Type II and V systems, Type VI systems also appear not to require a tracrRNA for processing pre-crRNA into crRNA. Similar to Type V systems, however, some Type VI systems (e.g., C2C2) appear to possess robust single-strand nonspecific nuclease (ribonuclease) activity activated by first-directed crRNA cleavage of a target RNA.

[0101] Due to their simpler architecture, Class 2 CRISPR-Cas have been more widely adopted for engineering and development as designer nuclease / genome editing applications.

[0102] One of the first adaptations of such a system Petition 870250090553, dated 03 / 10 / 2025, p. 33 / 262 30 / 251 for in vitro use involved (i) recombinantly purified full-length Cas9 (e.g., a Class 2, Type II Cas enzyme) isolated from S. pyogenes SF370, (ii) purified mature crRNA of ~42 nt containing a 5' sequence of ~20 nt complementary to the desired target DNA sequence to be cleaved followed by a 3' tracr binding sequence (the entire crRNA being in vitro transcribed from a synthetic DNA template containing a T7 promoter sequence); (iii) purified tracrRNA transcribed in vitro from a synthetic DNA template carrying a T7 promoter sequence, and (iv) Mg2+. A subsequently improved modified system involved crRNA from (ii) linked to the 5' end of (iii) by a linker (e.g., GAAA) to form a single fused synthetic guide RNA (sgRNA) capable of directing Cas9 to a target on its own.

[0103] Such modified systems can be adapted for use in mammalian cells by providing DNA vectors encoding (i) an ORF encoding Cas9 with an optimized codon (e.g., a Class 2, Type II Cas enzyme) under a suitable mammalian promoter with a C-terminal nuclear localization sequence (e.g., SV40 NLS) and a suitable polyadenylation signal (e.g., TK pA signal); and (ii) an ORF encoding an sgRNA (with a 5' sequence starting with G followed by 20 nt of a complementary targeting nucleic acid sequence attached to a 3' tracr binding sequence, a ligand, and the tracrRNA sequence) under a suitable Polymerase III promoter (e.g., the U6 promoter). MG Enzymes

[0104] These are described in this document, in certain Petition 870250090553, dated 03 / 10 / 2025, page 34 / 262 31 / 251 embodiments, the modified nuclease systems comprising an endonuclease and a modified guide polynucleotide. In some embodiments, the endonuclease is a Class 2, Type II endonuclease. In some embodiments, the endonuclease comprises a RuvC_III domain. In some embodiments, the endonuclease comprises an HNH domain. In some embodiments, the endonuclease is a double-stranded nuclease. In some embodiments, the endonuclease is catalytically killed. In some embodiments, the endonuclease is a double-stranded nuclease. In some embodiments, the endonuclease is modified. In some embodiments, the endonuclease is modified resulting in an endonuclease with nickase activity. In some embodiments, the modified endonuclease is a site-directed nickase.

[0105] In some embodiments, the endonuclease is an MG2 endonuclease. In some embodiments, the endonuclease is an MG4 endonuclease. In some embodiments, the endonuclease is an MG5 endonuclease. In some embodiments, the endonuclease is an MG6 endonuclease. In some embodiments, the endonuclease is an MG7 endonuclease. In some embodiments, the endonuclease is an MG16 endonuclease. In some embodiments, the endonuclease is an MG21 endonuclease. In some embodiments, the endonuclease is an MG23 endonuclease. In some embodiments, the endonuclease is an MG49 endonuclease. In some embodiments, the endonuclease is an MG86 endonuclease. In some embodiments, the endonuclease is an MG112 endonuclease. In some embodiments, the endonuclease is an MG116 endonuclease. In some embodiments, the endonuclease is an endonuclease. Petition 870250090553, dated 03 / 10 / 2025, page 35 / 262 32 / 251 MG171. In some embodiments, the endonuclease is an MG177 endonuclease. In some embodiments, the endonuclease is an MG183 endonuclease.

[0106] In some embodiments, the modified nuclease system is discovered through metagenomic sequencing. In some embodiments, metagenomic sequencing is performed on samples collected from various environments. In some embodiments, the environment is a human microbiome, an animal microbiome, a high-temperature environment, a low-temperature environment, or sediment.

[0107] In some embodiments, the endonuclease is an MG5 endonuclease (i.e., SEQ ID NOs: 1-5). In some embodiments, the endonuclease comprises a variant having at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99% identity with any of the SEQ ID NOs: 1-5. In some embodiments, the endonuclease comprises a sequence with at least about 70% identity to any of the SEQ ID NOs: 1-5. In some embodiments, the endonuclease comprises a sequence with at least about 75% identity to any of the SEQ ID NOs: 1-5.In some embodiments, the endonuclease comprises a sequence with at least about 80% identity to any of the SEQ ID NOs: 1-5. Petition 870250090553, dated 03 / 10 / 2025, p. 36 / 262 33 / 251 In some embodiments, the endonuclease comprises a sequence with at least about 85% identity to any of the SEQ ID NOs: 1-5. In some embodiments, the endonuclease comprises a sequence with at least about 90% identity to any of the SEQ ID NOs: 1-5. In some embodiments, the endonuclease comprises a sequence with at least about 95% identity to any of the SEQ ID NOs: 1-5. In some embodiments, the endonuclease comprises a sequence with at least about 96% identity to any of the SEQ ID NOs: 1-5. In some embodiments, the endonuclease comprises a sequence with at least about 97% identity to any of the SEQ ID NOs: 1-5. In some embodiments, the endonuclease comprises a sequence with at least about 98% identity to any of the SEQ ID NOs: 1-5.In some embodiments, the endonuclease comprises a sequence with at least about 99% identity to any of the SEQ ID NOs: 1-5. In some embodiments, the endonuclease comprises a sequence with 100% identity to any of the SEQ ID NOs: 1-5.

[0108] In some embodiments, the endonuclease is an MG21 endonuclease (i.e., SEQ ID NOs: 139-146 and 303). In some embodiments, the endonuclease comprises a variant having at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least Petition 870250090553, dated 03 / 10 / 2025, p. 37 / 262 34 / 251 approximately 98% or at least approximately 99% identity with any of the SEQ ID NOs: 139-146 and 303. In some embodiments, the endonuclease comprises a sequence with at least approximately 70% identity with any of the SEQ ID NOs: 139-146 and 303. In some embodiments, the endonuclease comprises a sequence with at least approximately 75% identity with any of the SEQ ID NOs: 139-146 and 303. In some embodiments, the endonuclease comprises a sequence with at least approximately 80% identity with any of the SEQ ID NOs: 139-146 and 303. In some embodiments, the endonuclease comprises a sequence with at least approximately 85% identity with any of the SEQ ID NOs: 139-146 and 303. In some embodiments, the endonuclease comprises a sequence with at least approximately 90% identity to either of the SEQ IDs 139146 and 303.In some embodiments, the endonuclease comprises a sequence with at least about 95% identity to any of the SEQ ID NOs: 139-146 and 303. In some embodiments, the endonuclease comprises a sequence with at least about 96% identity to any of the SEQ ID NOs: 139-146 and 303. In some embodiments, the endonuclease comprises a sequence with at least about 97% identity to any of the SEQ ID NOs: 139-146 and 303. In some embodiments, the endonuclease comprises a sequence with at least about 98% identity to any of the SEQ ID NOs: 139-146 and 303. In some embodiments, the endonuclease comprises a sequence with at least about 99% identity to any of the SEQ ID NOs: 139-146 and 303. In some embodiments, the The modified endonuclease comprises a sequence with 100% of... Petition 870250090553, dated 03 / 10 / 2025, p. 38 / 262 35 / 251 identity with any of the SEQ ID Nos: 139-146 and 303.

[0109] In some embodiments, the endonuclease is an MG23 endonuclease (i.e., SEQ ID NO: 304). In some embodiments, the endonuclease comprises a variant having at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99% identity with SEQ ID NO: 304. In some embodiments, the endonuclease comprises a sequence with at least about 70% identity with SEQ ID NO: 304. In some embodiments, the endonuclease comprises a sequence with at least about 75% match with SEQ ID NO: 304.In some embodiments, the endonuclease comprises a sequence with at least about 80% identity to SEQ ID NO: 304. In some embodiments, the endonuclease comprises a sequence with at least about 85% identity to SEQ ID NO: 304. In some embodiments, the endonuclease comprises a sequence with at least about 90% identity to SEQ ID NO: 304. In some embodiments, the endonuclease comprises a sequence with at least about 95% identity to SEQ ID NO: 304. In some embodiments, the endonuclease comprises a sequence with at least about 96% identity to SEQ ID NO: 304. In some embodiments, the endonuclease comprises a sequence with at least about 97% identity to SEQ ID NO: 304. Petition 870250090553, dated 03 / 10 / 2025, p. 39 / 262 36 / 251 In some embodiments, the endonuclease comprises a sequence with at least about 98% identity to SEQ ID NO: 304. In some embodiments, the endonuclease comprises a sequence with at least about 99% identity to SEQ ID NO: 304. In some embodiments, the modified endonuclease comprises a sequence with 100% identity to SEQ ID NO: 304.

[0110] In some embodiments, the endonuclease is an MG86 endonuclease (i.e., SEQ ID NO: 6). In some embodiments, the endonuclease comprises a variant having at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98% or at least approximately 99% match with SEQ ID. NO: 6. In some embodiments, the endonuclease comprises a sequence with at least about 70% identity to the SEQ ID NO: 6. In some embodiments, the endonuclease comprises a sequence with at least about 75% identity to SEQ ID NO: 6. In some embodiments, the endonuclease comprises a sequence with at least about 80% identity to SEQ ID NO: 6. In some embodiments, the endonuclease comprises a sequence with at least about 85% identity to SEQ ID NO: 6. In some embodiments, the endonuclease comprises a sequence with at least about 90% identity to SEQ ID NO: 6. In some embodiments, the endonuclease comprises a Petition 870250090553, dated 03 / 10 / 2025, p. 40 / 262 37 / 251 sequence with at least about 95% identity to SEQ ID NO: 6. In some embodiments, the endonuclease comprises a sequence with at least about 96% identity to SEQ ID NO: 6. In some embodiments, the endonuclease comprises a sequence with at least about 97% identity to SEQ ID NO: 6. In some embodiments, the endonuclease comprises a sequence with at least about 98% identity to SEQ ID NO: 6. In some embodiments, the endonuclease comprises a sequence with at least about 99% identity to SEQ ID NO: 6. In some embodiments, the modified endonuclease comprises a sequence with 100% identity to the SEQ. ID NO: 6.

[0111] In some embodiments, the endonuclease is an MG112 endonuclease (i.e., SEQ ID NOs: 7-11). In some embodiments, the endonuclease comprises a variant having at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99% identity with any of the SEQ ID NOs: 7-11. In some embodiments, the endonuclease comprises a sequence with at least about 70% identity to any of the SEQ IDs 7-11. In some embodiments, the endonuclease comprises a sequence with at least approximately 75% identity to any of the SEQ IDs 7-11. In some embodiments, Petition 870250090553, dated 03 / 10 / 2025, p. 41 / 262 38 / 251 The endonuclease comprises a sequence with at least about 80% identity to any of the SEQ ID NOs: 7-11. In some embodiments, the endonuclease comprises a sequence with at least about 85% identity to any of the SEQ ID NOs: 7-11. In some embodiments, the endonuclease comprises a sequence with at least about 90% identity to any of the SEQ ID NOs: 7-11. In some embodiments, the endonuclease comprises a sequence with at least about 95% identity to any of the SEQ ID NOs: 7-11. In some embodiments, the endonuclease comprises a sequence with at least about 96% identity to any of the SEQ ID NOs: 7-11. In some embodiments, the endonuclease comprises a sequence with at least about 97% identity to any of the SEQ ID NOs: 7-11. In some embodiments, the endonuclease comprises a sequence with at least about 98% identity to any of the SEQ IDs 7-11.In some embodiments, the endonuclease comprises a sequence with at least about 99% identity to any of the SEQ IDs NOs: 7-11. In some embodiments, the endonuclease comprises a sequence with 100% identity to any of the SEQ IDs NOs: 7-11.

[0112] In some embodiments, the endonuclease is an MG116 endonuclease (i.e., SEQ ID NOs: 12-14). In some embodiments, the endonuclease comprises a variant having at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, Petition 870250090553, dated 03 / 10 / 2025, p. 42 / 262 39 / 251 at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99% identity with any of the SEQ ID NOs: 12-14. In some embodiments, the endonuclease comprises a sequence with at least about 70% identity with any of the SEQ ID NOs: 12-14. In some embodiments, the endonuclease comprises a sequence with at least about 75% identity with any of the SEQ ID NOs: 12-14. In some embodiments, the endonuclease comprises a sequence with at least about 80% identity with any of the SEQ ID NOs: 12-14. In some embodiments, the endonuclease comprises a sequence with at least about 85% identity with any of the SEQ ID NOs: 12-14. In some embodiments, the endonuclease comprises a sequence with at least about 90% identity to any of the SEQ IDs NOs: 1214.In some embodiments, the endonuclease comprises a sequence with at least about 95% identity to any of the SEQ ID NOs: 12-14. In some embodiments, the endonuclease comprises a sequence with at least about 96% identity to any of the SEQ ID NOs: 12-14. In some embodiments, the endonuclease comprises a sequence with at least about 97% identity to any of the SEQ ID NOs: 12-14. In some embodiments, the endonuclease comprises a sequence with at least about 98% identity to any of the SEQ ID NOs: 12-14. In some embodiments, the endonuclease comprises a sequence with at least about 99% identity to any of the SEQ ID NOs: 12-14. In some embodiments, the endonuclease comprises a sequence with 100% identity to any of the SEQ ID NOs: 12-14. Petition 870250090553, dated 03 / 10 / 2025, p. 43 / 262 40 / 251 matching any of the SEQ ID Nos: 12-14.

[0113] In some embodiments, the endonuclease is an MG171 endonuclease (i.e., SEQ ID NOs: 105-109). In some embodiments, the endonuclease comprises a variant having at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99% identity with any of the SEQ ID NOs: 105-109. In some embodiments, the endonuclease comprises a sequence with at least about 70% identity to any of the SEQ IDs NOs: 105-109. In some embodiments, the endonuclease comprises a sequence with at least about 75% identity to any of the SEQ IDs NOs: 105-109.In some embodiments, the endonuclease comprises a sequence with at least about 80% identity to any of the SEQ ID NOs: 105-109. In some embodiments, the endonuclease comprises a sequence with at least about 85% identity to any of the SEQ ID NOs: 105-109. In some embodiments, the endonuclease comprises a sequence with at least about 90% identity to any of the SEQ ID NOs: 105-109. In some embodiments, the endonuclease comprises a sequence with at least about 95% identity to any of the SEQ ID NOs: 105-109. In some embodiments, the endonuclease comprises a sequence with at least about 96% identity to... Petition 870250090553, dated 03 / 10 / 2025, p. 44 / 262 41 / 251 any of the SEQ ID NOs: 105-109. In some embodiments, the endonuclease comprises a sequence with at least about 97% identity to any of the SEQ ID NOs: 105-109. In some embodiments, the endonuclease comprises a sequence with at least about 98% identity to any of the SEQ ID NOs: 105-109. In some embodiments, the endonuclease comprises a sequence with at least about 99% identity to any of the SEQ ID NOs: 105-109. In some embodiments, the endonuclease comprises a sequence with 100% identity to any of the SEQ ID NOs: 105-109.

[0114] In some embodiments, the endonuclease is an MG177 endonuclease (i.e., SEQ ID NOs: 110-116). In some embodiments, the endonuclease comprises a variant having at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99% identity with any of the SEQ ID NOs: 110-116. In some embodiments, the endonuclease comprises a sequence with at least about 70% identity to any of the SEQ IDs NOs: 110-116. In some embodiments, the endonuclease comprises a sequence with at least about 75% identity to any of the SEQ IDs NOs: 110-116.In some embodiments, the endonuclease comprises a sequence with at least about 80% identity to any of the... Petition 870250090553, dated 03 / 10 / 2025, p. 45 / 262 42 / 251 SEQ ID Nos: 110-116. In some embodiments, the endonuclease comprises a sequence with at least about 85% identity to any of the SEQ ID Nos: 110-116. In some embodiments, the endonuclease comprises a sequence with at least about 90% identity to any of the SEQ ID Nos: 110-116. In some embodiments, the endonuclease comprises a sequence with at least about 95% identity to any of the SEQ ID Nos: 110-116. In some embodiments, the endonuclease comprises a sequence with at least about 96% identity to any of the SEQ ID Nos: 110-116. In some embodiments, the endonuclease comprises a sequence with at least about 97% identity to any of the SEQ ID Nos: 110-116. In some embodiments, the endonuclease comprises a sequence with at least approximately 98% identity to any of the SEQ IDs 110-116.In some embodiments, the endonuclease comprises a sequence with at least about 99% identity to any of the SEQ ID NOs: 110-116. In some embodiments, the endonuclease comprises a sequence with 100% identity to any of the SEQ ID NOs: 110-116.

[0115] In some embodiments, the endonuclease is an MG183 endonuclease (i.e., SEQ ID NOs: 117-138). In some embodiments, the endonuclease comprises a variant having at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least Petition 870250090553, dated 03 / 10 / 2025, p. 46 / 262 43 / 251 approximately 96%, at least approximately 97%, at least approximately 98%, or at least approximately 99% identity with any of the SEQ ID NOs: 117-138. In some embodiments, the endonuclease comprises a sequence with at least approximately 70% identity with any of the SEQ ID NOs: 117-138. In some embodiments, the endonuclease comprises a sequence with at least approximately 75% identity with any of the SEQ ID NOs: 117-138. In some embodiments, the endonuclease comprises a sequence with at least approximately 80% identity with any of the SEQ ID NOs: 117-138. In some embodiments, the endonuclease comprises a sequence with at least approximately 85% identity with any of the SEQ ID NOs: 117-138. In some embodiments, the endonuclease comprises a sequence with at least about 90% identity to any of the SEQ IDs 117-138.In some embodiments, the endonuclease comprises a sequence with at least about 95% identity to any of the SEQ ID NOs: 117-138. In some embodiments, the endonuclease comprises a sequence with at least about 96% identity to any of the SEQ ID NOs: 117-138. In some embodiments, the endonuclease comprises a sequence with at least about 97% identity to any of the SEQ ID NOs: 117-138. In some embodiments, the endonuclease comprises a sequence with at least about 98% identity to any of the SEQ ID NOs: 117-138. In some embodiments, the endonuclease comprises a sequence with at least about 99% identity to any of the SEQ ID NOs: 117-138. In some embodiments, the endonuclease comprises a sequence with 100% identity. Petition 870250090553, dated 03 / 10 / 2025, p. 47 / 262 44 / 251 with any of the SEQ ID Nos: 117-138.

[0116] In some embodiments, the endonuclease comprises a nuclear localization sequence (NLS). In some embodiments, the NLS is at an N-terminus of the endonuclease. In some embodiments, the NLS is at a C-terminus of the endonuclease. In some embodiments, the NLS is at both an N-terminus and a C-terminus of the endonuclease.

[0117] In some embodiments, the NLS comprises a sequence of any of the SEQ ID NOs: 305-350, or a sequence with at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98% or at least approximately 99% identity with any of the SEQ IDs 305-350. In some embodiments, the NLS comprises a sequence with at least approximately 80% identity with SEQ IDs 305-350.In some modalities, the NLS comprises a sequence with at least approximately 85% identity to SEQ IDs 305-350. In some modalities, the NLS comprises a sequence with at least approximately 90% identity to SEQ IDs 305-350. In some modalities, the NLS comprises a sequence with at least approximately 91% identity to SEQ IDs 305-350. In some modalities, the NLS comprises a sequence with hairs. Petition 870250090553, dated 03 / 10 / 2025, p. 48 / 262 45 / 251 less approximately 92% identity with SEQ IDs 305-350. In some embodiments, the NLS comprises a sequence with at least approximately 93% identity with SEQ IDs 305-350. In some embodiments, the NLS comprises a sequence with at least approximately 94% identity with SEQ IDs 305-350. In some embodiments, the NLS comprises a sequence with at least approximately 95% identity with SEQ IDs 305-350. In some embodiments, the NLS comprises a sequence with at least approximately 96% identity with SEQ IDs 305-350. In some embodiments, the NLS comprises a sequence with at least approximately 97% identity with SEQ IDs 305-350. In some embodiments, the NLS comprises a sequence with at least approximately 98% identity to SEQ IDs 305-350. In some embodiments, the NLS comprises a sequence with at least approximately 99% identity to SEQ IDs 305-350.In some modalities, the NLS comprises a sequence with 100% identity with SEQ IDs 305-350. Table 1: Example of NLS sequences that can be used with CAS Effectors according to disclosure. Origin Amino acid sequence NLS SEQ ID NO: SV4 0 PKKKRKV 305 split nucleoplasmin NLS KRPAATKKAGQAKKKK 306 c-myc NLS PAAKRVKLD 307 c-myc NLS RQRRNELKRSP 308 hRNPA1 M9 NLS NQSSNFGPMKGGNFGGRSSGPYGGGGQYFAKPRNQGG Y 309 IBB domain Importin-alpha RMRIZFKNKGKDTAELRRRRVEVSVELRKAKKDEQIL KRRNV 310 Petition 870250090553, dated 03 / 10 / 2025, p. 49 / 262 46 / 251 Origin Amino acid sequence NLS SEQ ID NO: Myoma T protein VSRKRPRP 311 Myoma T protein PPKKARED 312 p53 PQPKKKPL 313 camundongo c-abl IV SALIKKKKKMAP 314 influenza virus NS1 15 DRLQKKR influenza virus 315 316 hepatitis virus delta antigen RKLKKKKKL 317 camundongo Mx1 protein REKKKFLKRR 318 human poly(ADP-ribose) polymerase KRKGDEVDGVDEVAKKSKKKK 319 steroid hormone (human) receptor glycocorticoid RKCLQAGMNLEARKTKK 320 5' SV40 NLS MAPKKKRKVGGGGS 321 3' SV40 1 NLS SGGAPKKKRKV 322 3' SV40 2 NLS SGGAPKKKRKV 323 3' SV40 3 NLS SV40 SGGAPKKKRKVSGGAPKKKRKVSGGAPKKKKV 324 5' Nucleoplasmina NLS MKRPAATKKAGQAKKKGGGGS 325 3' Nucleoplasmina 1 NLS SGGKRPAATKKAGQAKKKKK 326 3' Nucleoplasmina 2 NLSo SGGKRPATKKAGQKKKSGGKRPATKKAGQKKK K 327 3' Nucleoplasmin 3 NLS SGGKRPATKKAGQKKKSGGKRPATKKAGQKKKK KSGGKRPATKKAGQKKKKK 328 5' c-MAKCRPATKKAGQKKKK3 3' c-Myc 1 NLS SGGPAKRVKLD 330 Petition 870250090553, of 03 / 10 / 2025, p. 50 / 262 47 / 251 Origin Amino acid sequence NLS SEQ ID NO: 3' c-Myc 2 NLS SGGPAAKRVKLDSGGPAAKRVKLD 331 3' c-Myc 3 NLS SGGPAAKRVKLDSGGPAAKRVKLDSGGPAAKRVKLD 332 Synthetic NLS 5' Class 2-1 MQAAKRPRTTGGGGS 333 Synthetic NLS 3' Class 2-1 1 SGGQAAKRPRTT 334 Synthetic NLS 3' Class 2-1 2 SGGQAAKRPRTTSGGQAAKRPRTT 335 Synthetic NLS 5' Class 2-2 MRAAKRPRTTGGGGS 336 Synthetic NLS 3' Class 2-2 1 SGGRAAKRPRTT 337 Synthetic NLS 3' Class 2-2 2 SGGRAAKRPRTTSGGRAAKRPRTT 338 NLS Synthetic 5' Class 2-2 MRAAKRPRTTGGGGS 339 NLS Synthetic 3' Class 2-2 1 SGGRAAKRPRTT 340 NLS Synthetic 3' Class 2-2 2 SGGRAAKRPRTTSGGRAAKRPRTT 341 NLS Synthetic 5' Class 3 MAAAKRSWSMAFGGGGS 342 NLS Synthetic 3' Class 3 1 MSGGAAAKRSWSMAF 343 NLS Synthetic 3' Class 3 2 MSGGAAAKRSWSMAFMSGGAAAKRSWSMAF 344 NLS Synthetic 5' Class 4 MRAAKRKYFAVGGGGS 345 NLS Synthetic 3' Class 4 1 MSGGRAAKRKYFAV 346 NLS Synthetic 3' Class 4 2 MSGGRAAKRKYFAVMSGGRAAKRKYFAV 347 5' HCV NLS MPKPQRKTKRGGGGS 348 3' HCV NLS SGGPPRKKRTVV 349 3' hRNP A1 NLSSGGFGNYNNQSSNFGPMKGGNFGGRSSGPY 350 Petition 870250090553, dated 03 / 10 / 2025, p. 51 / 262 48 / 251 Guide polynucleotides

[0118] In some embodiments, the modified nuclease system disclosed in this document comprises a modified guide polynucleotide, for example, a guide ribonucleic acid (gRNA), a single gRNA or a double guide RNA.

[0119] In some embodiments, guide RNAs comprise several structural elements including, but not limited to: a spacer sequence that binds to the protospacer sequence (target sequence), a crRNA, and an optional tracrRNA. In some embodiments, the guide RNA comprises a crRNA comprising a spacer sequence. In some embodiments, the guide RNA comprises a tracrRNA or a modified tracrRNA.

[0120] In some embodiments, tracrRNA comprises a sequence comprising at least about 60–100 consecutive nucleotides with at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least approximately 85%, at least approximately 90%, at least approximately 91%, at least approximately 92%, at least approximately 93%, at least approximately 94%, at least approximately 95%, at least approximately 96%, at least approximately 97%, at least approximately 98%, or at least approximately 99% identity with the SEQ ID NO: 51. In some embodiments, the tracrRNA comprises a sequence comprising at least about 60-100 consecutive nucleotides with at least about 70% identity to SEQ ID NO: 51. In some embodiments, the Petition 870250090553, dated 03 / 10 / 2025, p. 52 / 262 49 / 251 tracrRNA comprises a sequence comprising at least about 60-100 consecutive nucleotides with at least about 75% identity to SEQ ID NO: 51. In some embodiments, tracrRNA comprises a sequence comprising at least about 60-100 consecutive nucleotides with at least about 80% identity to SEQ ID NO: 51. In some embodiments, tracrRNA comprises a sequence comprising at least about 60-100 consecutive nucleotides with at least about 85% identity to SEQ ID NO: 51. In some embodiments, tracrRNA comprises a sequence comprising at least about 60-100 consecutive nucleotides with at least about 90% identity to SEQ ID NO: 51. In some embodiments, tracrRNA comprises a sequence comprising at least about 60-100 consecutive nucleotides with at least less approximately 91% identity with SEQ ID NO: 51.In some embodiments, the tracrRNA comprises a sequence comprising at least about 60-100 consecutive nucleotides with at least about 92% identity to SEQ ID NO: 51. In some embodiments, the tracrRNA comprises a sequence comprising at least about 60-100 consecutive nucleotides with at least about 93% identity to SEQ ID NO: 51. In some embodiments, the tracrRNA comprises a sequence comprising at least about 60-100 consecutive nucleotides with at least about 94% identity to SEQ ID NO: 51. In some embodiments, the tracrRNA comprises a sequence comprising at least about 60-100 consecutive nucleotides with at least about 95% identity to SEQ ID NO: 51. In some embodiments... Petition 870250090553, dated 03 / 10 / 2025, p. 53 / 262 50 / 251 tracrRNA comprises a sequence comprising at least about 60-100 consecutive nucleotides with at least about 96% identity to SEQ ID NO: 51. In some embodiments, tracrRNA comprises a sequence comprising at least about 60-100 consecutive nucleotides with at least about 97% identity to SEQ ID NO: 51. In some embodiments, tracrRNA comprises a sequence comprising at least about 60-100 consecutive nucleotides with at least about 98% identity to SEQ ID NO: 51. In some embodiments, tracrRNA comprises a sequence comprising at least about 60-100 consecutive nucleotides with at least about 99% identity to SEQ ID NO: 51. In some embodiments, tracrRNA comprises a sequence comprising at least about 60-100 consecutive nucleotides. consecutive with 100% identity with SEQ ID NO: 51.

[0121] In some embodiments, the tracrRNA comprises a sequence with at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least approximately 94%, at least approximately 95%, at least approximately 96%, at least approximately 97%, at least approximately 98%, or at least approximately 99% identity with SEQ. ID NO: 51. In some embodiments, the tracrRNA comprises a sequence with at least approximately 70% identity to the Petition 870250090553, dated 03 / 10 / 2025, p. 54 / 262 51 / 251 SEQ ID NO: 51. In some embodiments, the tracrRNA comprises a sequence with at least about 75% identity to SEQ ID NO: 51. In some embodiments, the tracrRNA comprises a sequence with at least about 80% identity to SEQ ID NO: 51. In some embodiments, the tracrRNA comprises a sequence with at least about 85% identity to SEQ ID NO: 51. In some embodiments, the tracrRNA comprises a sequence with at least about 90% identity to SEQ ID NO: 51. In some embodiments, the tracrRNA comprises a sequence with at least about 91% identity to SEQ ID NO: 51. In some embodiments, the tracrRNA comprises a sequence with at least approximately 92% identity to SEQ ID NO: 51. In some embodiments, the tracrRNA comprises a sequence with at least about 93% identity to SEQ ID NO: 51. In some embodiments, the tracrRNA comprises a sequence with at least about 94% identity to SEQ ID NO: 51. In some embodiments, the tracrRNA comprises a sequence with at least about 95% identity to SEQ ID NO: 51. In some embodiments, the tracrRNA comprises a sequence with at least about 96% identity to SEQ ID NO: 51. In some embodiments, the tracrRNA comprises a sequence with at least about 97% identity to SEQ ID NO: 51. In some embodiments, the tracrRNA comprises a sequence with at least about 98% identity to SEQ ID NO: 51. In some embodiments, the tracrRNA comprises a sequence with at least approximately 99% identity to SEQ ID NO: 51. In some embodiments, the tracrRNA comprises a sequence with 100% identity to SEQ ID NO: 51. Petition 870250090553, dated 03 / 10 / 2025, page 55 / 262 52 / 251

[0122] In some embodiments, tracrRNA comprises a sequence comprising at least about 60–100 consecutive nucleotides with at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99% identity with any of the SEQ ID NOs: 215-222. In some embodiments, the tracrRNA comprises a sequence comprising at least about 60-100 consecutive nucleotides with at least about 70% identity with any of the SEQ ID NOs: 215-222. In some embodiments, the tracrRNA comprises a sequence comprising at least about 60-100 consecutive nucleotides with at least about 75% identity to any of the SEQ ID NOs: 215-222. In some embodiments, the tracrRNA comprises a sequence comprising at least about 60-100 consecutive nucleotides with at least about 80% identity to any of the SEQ ID NOs: 215-222.In some embodiments, the tracrRNA comprises a sequence comprising at least about 60-100 consecutive nucleotides with at least about 85% identity to any of the SEQ ID NOS: 215-222. In some embodiments, the tracrRNA comprises a sequence comprising at least about 60-100. Petition 870250090553, dated 03 / 10 / 2025, p. 56 / 262 53 / 251 consecutive nucleotides with at least about 90% identity to any of the SEQ ID NOs: 215-222. In some embodiments, the tracrRNA comprises a sequence comprising at least about 60-100 consecutive nucleotides with at least about 91% identity to any of the SEQ ID NOs: 215-222. In some embodiments, the tracrRNA comprises a sequence comprising at least about 60-100 consecutive nucleotides with at least about 92% identity to any of the SEQ ID NOs: 215-222. In some embodiments, the tracrRNA comprises a sequence comprising at least about 60-100 consecutive nucleotides with at least about 93% identity to any of the SEQ ID NOs: 215-222. In some embodiments, tracrRNA comprises a sequence comprising at least about 60-100 consecutive nucleotides with at least about 94% identity to any of the SEQ IDs 215-222.In some embodiments, the tracrRNA comprises a sequence comprising at least about 60-100 consecutive nucleotides with at least about 95% identity to any of the SEQ ID NOs: 215-222. In some embodiments, the tracrRNA comprises a sequence comprising at least about 60-100 consecutive nucleotides with at least about 96% identity to any of the SEQ ID NOs: 215-222. In some embodiments, the tracrRNA comprises a sequence comprising at least about 60-100 consecutive nucleotides with at least about 97% identity to any of the SEQ ID NOs: 215-222. In some embodiments, the tracrRNA comprises a sequence comprising at least about 60-100 consecutive nucleotides with at least... Petition 870250090553, dated 03 / 10 / 2025, p. 57 / 262 54 / 251 approximately 98% identity with any of the SEQ ID NOs: 215-222. In some embodiments, the tracrRNA comprises a sequence comprising at least about 60-100 consecutive nucleotides with at least about 99% identity with any of the SEQ ID NOs: 215-222. In some embodiments, the tracrRNA comprises a sequence comprising at least about 60-100 consecutive nucleotides with 100% identity with any of the SEQ ID NOs: 215-222.

[0123] In some embodiments, the tracrRNA comprises a sequence with at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99% identity with any of the SEQ IDs 215-222. In some embodiments, the tracrRNA comprises a sequence with at least about 70% identity with any of the SEQ IDs 215-222. In some embodiments, the tracrRNA comprises a sequence with at least approximately 75% identity to any of the SEQ IDs NOS: 215-222. In some embodiments, the tracrRNA comprises a sequence with at least approximately 80% identity to any of the SEQ IDs NOS: 215-222. In some embodiments, the tracrRNA comprises a sequence with Petition 870250090553, dated 03 / 10 / 2025, p. 58 / 262 55 / 251 at least approximately 85% identity with any of the SEQ IDs 215-222. In some embodiments, the tracrRNA comprises a sequence with at least approximately 90% identity with any of the SEQ IDs 215-222. In some embodiments, the tracrRNA comprises a sequence with at least approximately 91% identity with any of the SEQ IDs 215-222. In some embodiments, the tracrRNA comprises a sequence with at least approximately 92% identity with any of the SEQ IDs 215-222. In some embodiments, the tracrRNA comprises a sequence with at least approximately 93% identity with any of the SEQ IDs 215-222. In some embodiments, the tracrRNA comprises a sequence with at least approximately 94% identity with any of the SEQ IDs 215-222. In some embodiments, the tracrRNA comprises a sequence with at least about 95% identity to any of the SEQ IDs 215-222.In some embodiments, the tracrRNA comprises a sequence with at least about 96% identity to any of the SEQ IDs NOs: 215-222. In some embodiments, the tracrRNA comprises a sequence with at least about 97% identity to any of the SEQ IDs NOs: 215-222. In some embodiments, the tracrRNA comprises a sequence with at least about 98% identity to any of the SEQ IDs NOs: 215-222. In some embodiments, the tracrRNA comprises a sequence with at least about 99% identity to any of the SEQ IDs NOs: 215-222. In some embodiments, the tracrRNA comprises a sequence with 100% identity to any of the SEQ IDs NOs: 215-222.

[0124] In some modes, the tracrRNA Petition 870250090553, dated 03 / 10 / 2025, p. 59 / 262 56 / 251 comprises a sequence comprising at least about 60–100 consecutive nucleotides with at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least approximately 85%, at least approximately 90%, at least approximately 91%, at least approximately 92%, at least approximately 93%, at least approximately 94%, at least approximately 95%, at least approximately 96%, at least approximately 97%, at least approximately 98%, or at least approximately 99% identity with the SEQ ID NO: 52. In some embodiments, the tracrRNA comprises a sequence comprising at least about 60-100 consecutive nucleotides with at least about 70% identity to SEQ ID NO: 52. In some embodiments, the tracrRNA comprises a sequence comprising at least about 60-100 consecutive nucleotides with at least about 75% identity to SEQ ID NO: 52. In some embodiments, the tracrRNA comprises a sequence comprising at least about 60-100 consecutive nucleotides with at least about 80% identity to SEQ ID NO: 52. In some embodiments, the tracrRNA comprises a sequence comprising at least about 60-100 consecutive nucleotides with at least about 85% identity to SEQ ID NO: 52. In some embodiments, the tracrRNA comprises a sequence comprising at least about 60-100 Consecutive nucleotides with at least approximately 90% identity to SEQ ID NO: 52.In some forms, the tracrRNA comprises a sequence that... Petition 870250090553, dated 03 / 10 / 2025, p. 60 / 262 57 / 251 comprises at least about 60-100 consecutive nucleotides with at least about 91% identity to SEQ ID NO: 52. In some embodiments, the tracrRNA comprises a sequence comprising at least about 60-100 consecutive nucleotides with at least about 92% identity to SEQ ID NO: 52. In some embodiments, the tracrRNA comprises a sequence comprising at least about 60-100 consecutive nucleotides with at least about 93% identity to SEQ ID NO: 52. In some embodiments, the tracrRNA comprises a sequence comprising at least about 60-100 consecutive nucleotides with at least about 94% identity to SEQ ID NO: 52. In some embodiments, the tracrRNA comprises a sequence comprising at least about 60-100 consecutive nucleotides with at least about 95% match with SEQ ID NO: 52.In some embodiments, the tracrRNA comprises a sequence comprising at least about 60-100 consecutive nucleotides with at least about 96% identity to SEQ ID NO: 52. In some embodiments, the tracrRNA comprises a sequence comprising at least about 60-100 consecutive nucleotides with at least about 97% identity to SEQ ID NO: 52. In some embodiments, the tracrRNA comprises a sequence comprising at least about 60-100 consecutive nucleotides with at least about 98% identity to SEQ ID NO: 52. In some embodiments, the tracrRNA comprises a sequence comprising at least about 60-100 consecutive nucleotides with at least about 99% identity to SEQ ID NO: 52. In some embodiments, the tracrRNA comprises a sequence that... Petition 870250090553, dated 03 / 10 / 2025, p. 61 / 262 58 / 251 comprises at least approximately 60-100 consecutive nucleotides with 100% identity to SEQ ID NO: 52.

[0125] In some embodiments, the tracrRNA comprises a sequence with at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least approximately 94%, at least approximately 95%, at least approximately 96%, at least approximately 97%, at least approximately 98%, or at least approximately 99% identity with SEQ. ID NO: 52. In some embodiments, the tracrRNA comprises a sequence with at least approximately 70% identity to the SEQ ID NO: 52. In some embodiments, the tracrRNA comprises a sequence with at least about 75% identity to SEQ ID NO: 52. In some embodiments, the tracrRNA comprises a sequence with at least about 80% identity to SEQ ID NO: 52. In some embodiments, the tracrRNA comprises a sequence with at least about 85% identity to SEQ ID NO: 52. In some embodiments, the tracrRNA comprises a sequence with at least about 90% identity to SEQ ID NO: 52. In some embodiments, the tracrRNA comprises a sequence with at least about 91% identity to SEQ ID NO: 52. In some embodiments, the tracrRNA comprises a sequence with at least approximately 92% identity to SEQ ID NO: 52. In some embodiments, tracrRNA comprises a Petition 870250090553, dated 03 / 10 / 2025, p. 62 / 262 59 / 251 sequence with at least approximately 93% identity to SEQ ID NO: 52. In some embodiments, the tracrRNA comprises a sequence with at least approximately 94% identity to SEQ ID NO: 52. In some embodiments, the tracrRNA comprises a sequence with at least approximately 95% identity to SEQ ID NO: 52. In some embodiments, the tracrRNA comprises a sequence with at least approximately 96% identity to SEQ ID NO: 52. In some embodiments, the tracrRNA comprises a sequence with at least approximately 97% identity to SEQ ID NO: 52. In some embodiments, the tracrRNA comprises a sequence with at least approximately 98% identity to SEQ ID NO: 52. In some embodiments, the tracrRNA comprises a sequence with at least approximately 99% identity to SEQ ID NO: 52. In some embodiments, the tracrRNA comprises a sequence with 100% identity to SEQ ID NO: 52.

[0126] In some embodiments, tracrRNA comprises a sequence comprising at least about 60–100 consecutive nucleotides with at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least approximately 85%, at least approximately 90%, at least approximately 91%, at least approximately 92%, at least approximately 93%, at least approximately 94%, at least approximately 95%, at least approximately 96%, at least approximately 97%, at least approximately 98%, or at least approximately 99% identity with any of the SEQ ID Nos: 147-151. In some embodiments, Petition 870250090553, dated 03 / 10 / 2025, p. 63 / 262 60 / 251 tracrRNA comprises a sequence comprising at least about 60-100 consecutive nucleotides with at least about 70% identity to any of the SEQ ID NOs: 147-151. In some embodiments, tracrRNA comprises a sequence comprising at least about 60-100 consecutive nucleotides with at least about 75% identity to any of the SEQ ID NOs: 147-151. In some embodiments, tracrRNA comprises a sequence comprising at least about 60-100 consecutive nucleotides with at least about 80% identity to any of the SEQ ID NOs: 147-151. In some embodiments, tracrRNA comprises a sequence comprising at least about 60-100 consecutive nucleotides with at least about 85% identity to any of the SEQ IDs NOS: 147-151.In some embodiments, the tracrRNA comprises a sequence comprising at least about 60-100 consecutive nucleotides with at least about 90% identity to any of the SEQ ID NOs: 147-151. In some embodiments, the tracrRNA comprises a sequence comprising at least about 60-100 consecutive nucleotides with at least about 91% identity to any of the SEQ ID NOs: 147-151. In some embodiments, the tracrRNA comprises a sequence comprising at least about 60-100 consecutive nucleotides with at least about 92% identity to any of the SEQ ID NOs: 147-151. In some embodiments, the tracrRNA comprises a sequence comprising at least about 60-100 consecutive nucleotides with at least about 93% identity to any of the SEQ IDs 147-151. In some embodiments, the tracrRNA comprises a sequence that... Petition 870250090553, dated 03 / 10 / 2025, p. 64 / 262 61 / 251 comprises at least about 60-100 consecutive nucleotides with at least about 94% identity to any of the SEQ ID NOs: 147-151. In some embodiments, the tracrRNA comprises a sequence comprising at least about 60-100 consecutive nucleotides with at least about 95% identity to any of the SEQ ID NOs: 147-151. In some embodiments, the tracrRNA comprises a sequence comprising at least about 60-100 consecutive nucleotides with at least about 96% identity to any of the SEQ ID NOs: 147-151. In some embodiments, the tracrRNA comprises a sequence comprising at least about 60-100 consecutive nucleotides with at least about 97% identity to any of the SEQ ID NOs: 147-151.In some embodiments, the tracrRNA comprises a sequence comprising at least about 60-100 consecutive nucleotides with at least about 98% identity to any of the SEQ ID NOs: 147-151. In some embodiments, the tracrRNA comprises a sequence comprising at least about 60-100 consecutive nucleotides with at least about 99% identity to any of the SEQ ID NOs: 147-151. In some embodiments, the tracrRNA comprises a sequence comprising at least about 60-100 consecutive nucleotides with 100% identity to any of the SEQ ID NOs: 147-151.

[0127] In some embodiments, the tracrRNA comprises a sequence with at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, in at least about 55%, by Petition 870250090553, dated 03 / 10 / 2025, p. 65 / 262 62 / 251 less approximately 60%, at least approximately 65%, at least approximately 70%, at least approximately 75%, at least approximately 80%, at least approximately 85%, at least approximately 90%, at least approximately 91%, at least approximately 92%, at least approximately 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99% identity with any of the SEQ IDs NOs: 147-151. In some embodiments, the tracrRNA comprises a sequence with at least about 70% identity with any of the SEQ IDs NOs: 147-151. In some embodiments, the tracrRNA comprises a sequence with at least about 75% identity with any of the SEQ IDs NOs: 147-151. In some embodiments, the tracrRNA comprises a sequence with at least about 80% identity with any of the SEQ IDs NOs: 147-151. In some embodiments, the tracrRNA comprises a sequence with at least about 85% identity to any of the SEQ IDs NOs: 147-151. In some embodiments, the tracrRNA comprises a sequence with at least about 90% identity to any of the SEQ IDs NOs: 147-151.In some embodiments, the tracrRNA comprises a sequence with at least about 91% identity to any of the SEQ IDs NOS: 147-151. In some embodiments, the tracrRNA comprises a sequence with at least about 92% identity to any of the SEQ IDs NOS: 147-151. In some embodiments, the tracrRNA comprises a sequence with at least about 93% identity to any of the SEQ IDs NOS: 147-151. In some embodiments, the tracrRNA comprises a sequence with at least about 94% identity to any of the SEQ IDs NOS: 147-151. Petition 870250090553, dated 03 / 10 / 2025, p. 66 / 262 63 / 251 In some embodiments, the tracrRNA comprises a sequence with at least about 95% identity to any of the SEQ IDs NOs: 147-151. In some embodiments, the tracrRNA comprises a sequence with at least about 96% identity to any of the SEQ IDs NOs: 147-151. In some embodiments, the tracrRNA comprises a sequence with at least about 97% identity to any of the SEQ IDs NOs: 147-151. In some embodiments, the tracrRNA comprises a sequence with at least about 98% identity to any of the SEQ IDs NOs: 147-151. In some embodiments, the tracrRNA comprises a sequence with at least about 99% identity to any of the SEQ IDs NOs: 147-151. In some embodiments, the tracrRNA comprises a sequence with 100% identity to any of the SEQ IDs NOS: 147-151.

[0128] In some embodiments, tracrRNA comprises a sequence comprising at least about 60–100 consecutive nucleotides with at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99% identity with any of the SEQ ID Nos: 157-163. In some embodiments, the tracrRNA comprises a sequence comprising at least Petition 870250090553, dated 03 / 10 / 2025, p. 67 / 262 64 / 251 approximately 60-100 consecutive nucleotides with at least approximately 70% identity to any of the SEQ ID NOs: 157-163. In some embodiments, the tracrRNA comprises a sequence comprising at least approximately 60-100 consecutive nucleotides with at least approximately 75% identity to any of the SEQ ID NOs: 157-163. In some embodiments, the tracrRNA comprises a sequence comprising at least approximately 60-100 consecutive nucleotides with at least approximately 80% identity to any of the SEQ ID NOs: 157-163. In some embodiments, the tracrRNA comprises a sequence comprising at least approximately 60-100 consecutive nucleotides with at least approximately 85% identity to any of the SEQ ID NOs: 157-163. In some embodiments, tracrRNA comprises a sequence comprising at least about 60-100 consecutive nucleotides with at least about 90% identity to any of the SEQ IDs NOS: 157-163.In some embodiments, the tracrRNA comprises a sequence comprising at least about 60-100 consecutive nucleotides with at least about 91% identity to any of the SEQ ID NOs: 157-163. In some embodiments, the tracrRNA comprises a sequence comprising at least about 60-100 consecutive nucleotides with at least about 92% identity to any of the SEQ ID NOs: 157-163. In some embodiments, the tracrRNA comprises a sequence comprising at least about 60-100 consecutive nucleotides with at least about 93% identity to any of the SEQ ID NOs: 157-163. In some embodiments, the tracrRNA comprises a sequence comprising at least about 60-100 nucleotides. Petition 870250090553, dated 03 / 10 / 2025, p. 68 / 262 65 / 251 consecutive nucleotides with at least approximately 94% identity to any of the SEQ ID NOs: 157-163. In some embodiments, the tracrRNA comprises a sequence comprising at least approximately 60-100 consecutive nucleotides with at least approximately 95% identity to any of the SEQ ID NOs: 157-163. In some embodiments, the tracrRNA comprises a sequence comprising at least approximately 60-100 consecutive nucleotides with at least approximately 96% identity to any of the SEQ ID NOs: 157-163. In some embodiments, the tracrRNA comprises a sequence comprising at least approximately 60-100 consecutive nucleotides with at least approximately 97% identity to any of the SEQ ID NOs: 157-163. In some embodiments, tracrRNA comprises a sequence comprising at least about 60-100 consecutive nucleotides with at least about 98% identity to any of the SEQ IDs NOS: 157-163.In some embodiments, the tracrRNA comprises a sequence comprising at least about 60-100 consecutive nucleotides with at least about 99% identity to any of the SEQ ID NOs: 157-163. In some embodiments, the tracrRNA comprises a sequence comprising at least about 60-100 consecutive nucleotides with 100% identity to any of the SEQ ID NOs: 157-163.

[0129] In some embodiments, the tracrRNA comprises a sequence with at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about Petition 870250090553, dated 03 / 10 / 2025, p. 69 / 262 66 / 251 of 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99% identity with any of the SEQ IDs 157-163. In some embodiments, the tracrRNA comprises a sequence with at least about 70% identity with any of the SEQ IDs 157-163. In some embodiments, the tracrRNA comprises a sequence with at least about 75% identity with any of the SEQ IDs 157-163. In some embodiments, the tracrRNA comprises a sequence with at least about 80% identity with any of the SEQ IDs 157-163. In some embodiments, the tracrRNA comprises a sequence with at least about 85% identity to any of the SEQ IDs NOs: 157-163. In some embodiments, the tracrRNA comprises a sequence with at least about 90% identity to any of the SEQ IDs NOs: 157-163.In some embodiments, the tracrRNA comprises a sequence with at least about 91% identity to any of the SEQ IDs NOs: 157-163. In some embodiments, the tracrRNA comprises a sequence with at least about 92% identity to any of the SEQ IDs NOs: 157-163. In some embodiments, the tracrRNA comprises a sequence with at least about 93% identity to any of the SEQ IDs NOs: 157-163. In some embodiments, the tracrRNA comprises a sequence with at least about 94% identity to any of the SEQ IDs NOs: 157-163. In some embodiments, the tracrRNA comprises a sequence with... Petition 870250090553, dated 03 / 10 / 2025, p. 70 / 262 67 / 251 at least approximately 95% identity with any of the SEQ IDs NOS: 157-163. In some embodiments, the tracrRNA comprises a sequence with at least approximately 96% identity with any of the SEQ IDs NOS: 157-163. In some embodiments, the tracrRNA comprises a sequence with at least approximately 97% identity with any of the SEQ IDs NOS: 157-163. In some embodiments, the tracrRNA comprises a sequence with at least approximately 98% identity with any of the SEQ IDs NOS: 157-163. In some embodiments, the tracrRNA comprises a sequence with at least approximately 99% identity with any of the SEQ IDs NOS: 157-163. In some embodiments, the tracrRNA comprises a sequence with 100% identity with any of the SEQ IDs NOS: 157-163.

[0130] In some embodiments, tracrRNA comprises a sequence comprising at least about 60–100 consecutive nucleotides with at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99% identity with any of the SEQ IDs NOS: 171-192. In some embodiments, the tracrRNA comprises a sequence comprising at least about 60-100 consecutive nucleotides with at least Petition 870250090553, dated 03 / 10 / 2025, p. 71 / 262 68 / 251 approximately 70% identity with any of the SEQ ID NOs: 171-192. In some embodiments, the tracrRNA comprises a sequence comprising at least about 60-100 consecutive nucleotides with at least about 75% identity with any of the SEQ ID NOs: 171-192. In some embodiments, the tracrRNA comprises a sequence comprising at least about 60-100 consecutive nucleotides with at least about 80% identity with any of the SEQ ID NOs: 171-192. In some embodiments, the tracrRNA comprises a sequence comprising at least about 60-100 consecutive nucleotides with at least about 85% identity with any of the SEQ ID NOs: 171-192. In some embodiments, tracrRNA comprises a sequence comprising at least about 60-100 consecutive nucleotides with at least about 90% identity to any of the SEQ IDs 171-192.In some embodiments, the tracrRNA comprises a sequence comprising at least about 60-100 consecutive nucleotides with at least about 91% identity to any of the SEQ ID NOs: 171-192. In some embodiments, the tracrRNA comprises a sequence comprising at least about 60-100 consecutive nucleotides with at least about 92% identity to any of the SEQ ID NOs: 171-192. In some embodiments, the tracrRNA comprises a sequence comprising at least about 60-100 consecutive nucleotides with at least about 93% identity to any of the SEQ ID NOs: 171-192. In some embodiments, the tracrRNA comprises a sequence comprising at least about 60-100 consecutive nucleotides with at least about 94% identity to... Petition 870250090553, dated 03 / 10 / 2025, p. 72 / 262 69 / 251 any of the SEQ ID NOs: 171-192. In some embodiments, the tracrRNA comprises a sequence comprising at least about 60-100 consecutive nucleotides with at least about 95% identity to any of the SEQ ID NOs: 171-192. In some embodiments, the tracrRNA comprises a sequence comprising at least about 60-100 consecutive nucleotides with at least about 96% identity to any of the SEQ ID NOs: 171-192. In some embodiments, the tracrRNA comprises a sequence comprising at least about 60-100 consecutive nucleotides with at least about 97% identity to any of the SEQ ID NOs: 171-192. In some embodiments, tracrRNA comprises a sequence comprising at least about 60-100 consecutive nucleotides with at least about 98% identity to any of the SEQ IDs 171-192.In some embodiments, the tracrRNA comprises a sequence comprising at least about 60-100 consecutive nucleotides with at least about 99% identity to any of the SEQ ID NOs: 171-192. In some embodiments, the tracrRNA comprises a sequence comprising at least about 60-100 consecutive nucleotides with 100% identity to any of the SEQ ID NOs: 171-192.

[0131] In some embodiments, the tracrRNA comprises a sequence with at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, Petition 870250090553, dated 03 / 10 / 2025, p. 73 / 262 70 / 251 at least about 85%, at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99% identity with any of the SEQ IDs NOs: 171-192. In some embodiments, the tracrRNA comprises a sequence with at least about 70% identity with any of the SEQ IDs NOs: 171-192. In some embodiments, the tracrRNA comprises a sequence with at least about 75% identity with any of the SEQ IDs NOs: 171-192. In some embodiments, the tracrRNA comprises a sequence with at least about 80% identity to any of the SEQ IDs NOs: 171-192. In some embodiments, the tracrRNA comprises a sequence with at least about 85% identity to any of the SEQ IDs NOs: 171-192.In some embodiments, the tracrRNA comprises a sequence with at least about 90% identity to any of the SEQ IDs NOs: 171-192. In some embodiments, the tracrRNA comprises a sequence with at least about 91% identity to any of the SEQ IDs NOs: 171-192. In some embodiments, the tracrRNA comprises a sequence with at least about 92% identity to any of the SEQ IDs NOs: 171-192. In some embodiments, the tracrRNA comprises a sequence with at least about 93% identity to any of the SEQ IDs NOs: 171-192. In some embodiments, the tracrRNA comprises a sequence with at least about 94% identity to any of the SEQ IDs NOs: 171-192. In some embodiments, the tracrRNA comprises a sequence with at least about 95% identity to any of the... Petition 870250090553, dated 03 / 10 / 2025, p. 74 / 262 71 / 251 SEQ ID Nos: 171-192. In some embodiments, the tracrRNA comprises a sequence with at least about 96% identity to any of the SEQ ID Nos: 171-192. In some embodiments, the tracrRNA comprises a sequence with at least about 97% identity to any of the SEQ ID Nos: 171-192. In some embodiments, the tracrRNA comprises a sequence with at least about 98% identity to any of the SEQ ID Nos: 171-192. In some embodiments, the tracrRNA comprises a sequence with at least about 99% identity to any of the SEQ ID Nos: 171-192. In some embodiments, the tracrRNA comprises a sequence with 100% identity to any of the SEQ ID Nos: 171-192.

[0132] In some embodiments, the modified nuclease system disclosed in this document comprises a modified guide polynucleotide, for example, a guide ribonucleic acid (gRNA), a single gRNA or a double guide RNA.

[0133] In some embodiments, the modified guide polynucleotide (i.e., SEQ ID NO: 50) functions with an MG112 nuclease. In some embodiments, the modified guide polynucleotide comprises a sequence with at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, Petition 870250090553, dated 03 / 10 / 2025, p. 75 / 262 72 / 251 at least about 98%, or at least about 99% identity with SEQ ID NO: 50. In some embodiments, the modified guide polynucleotide comprises a sequence with at least 70% identity with SEQ ID NO: 50. In some embodiments, the modified guide polynucleotide comprises a sequence with at least 75% identity with SEQ ID NO: 50. In some embodiments, the modified guide polynucleotide comprises a sequence with at least 80% identity with SEQ ID NO: 50. In some embodiments, the modified guide polynucleotide comprises a sequence with at least 85% identity with SEQ ID NO: 50. In some embodiments, the modified guide polynucleotide comprises a sequence with at least 90% identity with SEQ ID NO: 50. In some embodiments, the modified guide polynucleotide comprises a sequence with at least 91% identity with SEQ ID NO: 50.In some embodiments, the modified guide polynucleotide comprises a sequence with at least 92% identity to SEQ ID NO: 50. In some embodiments, the modified guide polynucleotide comprises a sequence with at least 93% identity to SEQ ID NO: 50. In some embodiments, the modified guide polynucleotide comprises a sequence with at least 94% identity to SEQ ID NO: 50. In some embodiments, the modified guide polynucleotide comprises a sequence with at least 95% identity to SEQ ID NO: 50. In some embodiments, the modified guide polynucleotide comprises a sequence with at least 96% identity to SEQ ID NO: 50. In some embodiments, the modified guide polynucleotide comprises a sequence with at least 97% identity to SEQ ID NO: 50. In some embodiments, the... Petition 870250090553, dated 03 / 10 / 2025, p. 76 / 262 73 / 251 The modified guide polynucleotide comprises a sequence with at least 98% identity to SEQ ID NO: 50. In some embodiments, the modified guide polynucleotide comprises a sequence with at least 99% identity to SEQ ID NO: 50. In some embodiments, the modified guide polynucleotide comprises a sequence with 100% identity to SEQ ID NO: 50.

[0134] In some embodiments, the modified guide polynucleotide (i.e., SEQ ID NO: 231-240) functions with an MG171 nuclease. In some embodiments, the modified guide polynucleotide comprises a sequence with at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99% identity with any of the SEQ IDs NOS: 231-240. In some embodiments, the modified guide polynucleotide comprises a sequence with at least 70% identity with any of the SEQ IDs NOS: 231-240. In some embodiments, the modified guide polynucleotide comprises a sequence with at least 75% identity with any of the SEQ IDs NOS: 231-240. In some embodiments, the modified guide polynucleotide comprises a sequence with at least 80% identity with any Petition 870250090553, dated 03 / 10 / 2025, p. 77 / 262 74 / 251 one of the SEQ IDs 231-240. In some embodiments, the modified guide polynucleotide comprises a sequence with at least 85% identity to any of the SEQ IDs 231-240. In some embodiments, the modified guide polynucleotide comprises a sequence with at least 90% identity to any of the SEQ IDs 231-240. In some embodiments, the modified guide polynucleotide comprises a sequence with at least 91% identity to any of the SEQ IDs 231-240. In some embodiments, the modified guide polynucleotide comprises a sequence with at least 92% identity to any of the SEQ IDs 231-240. In some embodiments, the modified guide polynucleotide comprises a sequence with at least 93% identity to any of the SEQ IDs 231-240. In some embodiments, the modified guide polynucleotide comprises a sequence with at least 94% identity to any of the SEQ IDs 231-240.In some embodiments, the modified guide polynucleotide comprises a sequence with at least 95% identity to any of the SEQ IDs NOs: 231-240. In some embodiments, the modified guide polynucleotide comprises a sequence with at least 96% identity to any of the SEQ IDs NOs: 231-240. In some embodiments, the modified guide polynucleotide comprises a sequence with at least 97% identity to any of the SEQ IDs NOs: 231-240. In some embodiments, the modified guide polynucleotide comprises a sequence with at least 98% identity to any of the SEQ IDs NOs: 231-240. In some embodiments, the modified guide polynucleotide comprises a sequence with at least 99% identity. Petition 870250090553, dated 03 / 10 / 2025, p. 78 / 262 75 / 251 with any of the SEQ IDs 231-240. In some embodiments, the modified guide polynucleotide comprises a sequence with 100% identity to any of the SEQ IDs 231-240.

[0135] In some embodiments, the modified guide polynucleotide (i.e., SEQ ID NO: 241-250) functions with an MG177 nuclease. In some embodiments, the modified guide polynucleotide comprises a sequence with at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99% identity with any of the SEQ IDs NOs: 241-250. In some embodiments, the modified guide polynucleotide comprises a sequence with at least 70% identity with any of the SEQ IDs NOs: 241-250. In some embodiments, the modified guide polynucleotide comprises a sequence with at least 75% identity with any of the SEQ IDs NOs: 241-250. In some embodiments, the modified guide polynucleotide comprises a sequence with at least 80% identity to any of the SEQ IDs 241-250. In some embodiments, the modified guide polynucleotide comprises a sequence with at least 85% identity to any of the SEQ IDs Petition 870250090553, dated 03 / 10 / 2025, p. 79 / 262 76 / 251 In some embodiments, the modified guide polynucleotide comprises a sequence with at least 90% identity to any of the SEQ IDs 241-250. In some embodiments, the modified guide polynucleotide comprises a sequence with at least 91% identity to any of the SEQ IDs 241-250. In some embodiments, the modified guide polynucleotide comprises a sequence with at least 92% identity to any of the SEQ IDs 241-250. In some embodiments, the modified guide polynucleotide comprises a sequence with at least 93% identity to any of the SEQ IDs 241-250. In some embodiments, the modified guide polynucleotide comprises a sequence with at least 94% identity to any of the SEQ IDs 241-250. In some embodiments, the modified guide polynucleotide comprises a sequence with at least 95% identity to any of the SEQ IDs 241-250.In some embodiments, the modified guide polynucleotide comprises a sequence with at least 96% identity to any of the SEQ IDs 241-250. In some embodiments, the modified guide polynucleotide comprises a sequence with at least 97% identity to any of the SEQ IDs 241-250. In some embodiments, the modified guide polynucleotide comprises a sequence with at least 98% identity to any of the SEQ IDs 241-250. In some embodiments, the modified guide polynucleotide comprises a sequence with at least 99% identity to any of the SEQ IDs 241-250. In some embodiments, the modified guide polynucleotide comprises a sequence with 100% identity to any of the... Petition 870250090553, dated 03 / 10 / 2025, p. 80 / 262 77 / 251 SEQ ID NOS: 241-250.

[0136] In some embodiments, the modified guide polynucleotide comprises synthetic nucleotides or modified nucleotides. In some embodiments, the modified guide polynucleotide comprises one or more internucleoside linkers modified from the natural phosphodiester. In some embodiments, all internucleoside linkers of the modified guide polynucleotide, or contiguous nucleotide sequence thereof, are modified. For example, in some embodiments, the internucleoside linker comprises Sulfur (S), such as a phosphorothioate internucleoside linker.

[0137] In some embodiments, the modified guide polynucleotide comprises modifications in a ribose sugar or nucleobase. In some embodiments, the modified guide polynucleotide comprises one or more nucleosides comprising a modified sugar moiety, wherein the modified sugar moiety is a modification of the sugar moiety when compared to the ribose sugar moiety found in deoxyribose nucleic acid (DNA) and RNA. In some embodiments, the modification is within the ribose ring structure. Exemplary modifications include, but are not limited to, substitution with a hexose ring (HNA), a bicyclic ring with a biradical bridge between carbons C2 and C4 in the ribose ring (e.g., locked nucleic acids (LNA)), or an unlinked ribose ring that normally lacks a linkage between carbons C2 and C3 (e.g., UNA).In some embodiments, the sugar-modified nucleosides comprise bicyclohexose nucleic acids or tricyclic nucleic acids. In some embodiments, the... Petition 870250090553, dated 03 / 10 / 2025, p. 81 / 262 78 / 251 Modified nucleosides comprise nucleosides in which the sugar moiety is replaced by a non-sugar moiety, for example, peptide nucleic acids (PNA) or morpholino nucleic acids.

[0138] In some embodiments, the modified guide polynucleotide comprises one or more modified sugars. In some embodiments, the sugar modifications comprise modifications made by altering the substituent groups on the ribose ring to groups other than hydrogen, or the 2'-OH group naturally found in DNA and RNA nucleosides. In some embodiments, the substituents are introduced at the 2', 3', 4' or 5' positions. 5', or combinations thereof. In some embodiments, nucleosides with modified sugar moieties comprise 2'-modified nucleosides, for example, 2'-substituted nucleosides. A 2'-sugar-modified nucleoside, in some embodiments, is a nucleoside having a substituent other than -H or -OH at the 2' position (2'-substituted nucleoside) or comprises a 2'-linked biradical and comprises 2'-substituted nucleosides and LNA nucleosides (2'-4' biradical linkage). Examples of modified nucleosides substituted at 2' include, but are not limited to, 2'-O-alkyl-RNA, 2'-O-methyl-RNA, 2'-alkoxy-RNA, 2'-O-methoxyethyl-RNA (MOE), 2'-amino-DNA nucleosides, 2'-fluoro-RNA, and 2'-F-ANA. In some embodiments, the modification at the ribose group comprises a modification at the 2' position of the ribose group. In some embodiments, the modification at the 2' position of the ribose group is selected from the group consisting of 2'-O-methyl, 2'-fluoro, 2'-deoxy, and 2'O-(2-methoxyethyl). Petition 870250090553, dated 03 / 10 / 2025, page 82 / 262 79 / 251

[0139] In some embodiments, the modified guide polynucleotide comprises one or more modified sugars. In some embodiments, the modified guide polynucleotide comprises only modified sugars. In certain embodiments, the modified guide polynucleotide comprises more than about 10%, 25%, 50%, 75%, or 90% of modified sugars. In some embodiments, the modified sugar is a bicyclic sugar. In some embodiments, the modified sugar comprises a 2'-O-methoxyethyl group. In some embodiments, the modified guide polynucleotide comprises internucleoside linker modifications and nucleoside modifications.

[0140] In some embodiments, the modified guide polynucleotide comprises a sequence complementary to a eukaryotic, fungal, plant, mammalian, or human genomic polynucleotide sequence. In some embodiments, the modified guide polynucleotide comprises a sequence complementary to a eukaryotic genomic polynucleotide sequence. In some embodiments, the modified guide polynucleotide comprises a sequence complementary to a fungal genomic polynucleotide sequence. In some embodiments, the modified guide polynucleotide comprises a sequence complementary to a plant genomic polynucleotide sequence. In some embodiments, the modified guide polynucleotide comprises a sequence complementary to a mammalian genomic polynucleotide sequence. In some embodiments, the modified guide polynucleotide comprises a sequence complementary to a human genomic polynucleotide sequence.

[0141] In some forms, the polynucleotide Petition 870250090553, dated 03 / 10 / 2025, page 83 / 262 The modified 80 / 251 guide is 30-250 nucleotides long. In some embodiments, the modified guide polynucleotide is more than 90 nucleotides long. In some embodiments, the modified guide polynucleotide is less than 245 nucleotides long. In some embodiments, the modified guide polynucleotide is 30, 40, 50, 60, 70, 80, 90, 100, 120, 140, 160, 180, 200, 220, 240 or more than 240 nucleotides in length. In some embodiments, the modified guide polynucleotide has approximately 30 to approximately 40, approximately 30 to approximately 50, approximately 30 to approximately 60, approximately 30 to approximately 70, approximately 30 to approximately 80, approximately 30 to approximately 90, approximately 30 to approximately 100, approximately 30 to approximately 120, approximately 30 to approximately 140, approximately 30 to approximately 160, approximately 30 to approximately 180, approximately 30 to approximately 200, approximately 30 to approximately 220, approximately 30 to approximately 240, approximately 50 to approximately 60, approximately 50 to approximately 70, approximately 50 to approximately 80, approximately 50 to approximately 90, approximately 50 to approximately 100, about 50 to about 120, about 50 to about 140, about 50 to about 160, about 50 to about 180, about 50 to about 200, about 50 to about 220, about 50 to about 240, about 100 to about 120, about 100 to about 140, about 100 to about 160, about 100 to about 180,approximately 100 to approximately 200, approximately 100 to approximately 220, approximately 100 to approximately 240, approximately 160 to approximately 180, approximately 160 to approximately 200, approximately 160 to approximately 220, or approximately 160 to approximately 240 nucleotides in length. MG Systems

[0142] Modified nuclease systems are described in certain embodiments in this document. Petition 870250090553, dated 03 / 10 / 2025, p. 84 / 262 81 / 251 comprise an endonuclease comprising a modified guide polynucleotide. In some embodiments, the modified guide polynucleotide comprises a tracrRNA. In some embodiments, the modified guide polynucleotide comprises a single guide nucleic acid (e.g., gRNA). In a polynucleotide, when referring to a T, a T means U (Uracil) in RNA and T (Thymine) in DNA.

[0143] In some embodiments, the modified nuclease system comprises an endonuclease comprising a sequence with at least about 70% identity to any of the SEQ ID NOs: 139-146 and 303 and a modified polynucleotide comprising a sequence with at least about 70% identity to any of the SEQ ID NOs: 215-222. In some embodiments, the modified nuclease system comprises an endonuclease comprising a sequence with at least about 75% identity to any of the SEQ ID NOs: 139-146 and 303 and a modified polynucleotide comprising a sequence with at least about 75% identity to any of the SEQ ID NOs: 215-222.In some embodiments, the modified nuclease system comprises an endonuclease comprising a sequence with at least about 80% identity to any of the SEQ ID NOs: 139-146 and 303 and a modified polynucleotide comprising a sequence with at least about 80% identity to any of the SEQ ID NOs: 215-222. In some embodiments, the modified nuclease system comprises an endonuclease comprising a sequence with at least about 85% identity to any of the SEQ ID NOs: 139-146 and 303 and a modified polynucleotide comprising a sequence. Petition 870250090553, dated 03 / 10 / 2025, page 85 / 262 82 / 251 with at least about 85% identity to any of the SEQ ID NOs: 215-222. In some embodiments, the modified nuclease system comprises an endonuclease comprising a sequence with at least about 90% identity to any of the SEQ ID NOs: 139-146 and 303 and a modified polynucleotide comprising a sequence with at least about 90% identity to any of the SEQ ID NOs: 215-222. In some embodiments, the modified nuclease system comprises an endonuclease comprising a sequence with at least about 95% identity to any of the SEQ ID NOs: 139-146 and 303 and a modified polynucleotide comprising a sequence with at least about 95% identity to any of the SEQ ID NOs: 215-222.In some embodiments, the modified nuclease system comprises an endonuclease comprising a sequence with at least about 96% identity to any of the SEQ ID NOs: 139-146 and 303 and a modified polynucleotide comprising a sequence with at least about 96% identity to any of the SEQ ID NOs: 215-222. In some embodiments, the modified nuclease system comprises an endonuclease comprising a sequence with at least about 97% identity to any of the SEQ ID NOs: 139-146 and 303 and a modified polynucleotide comprising a sequence with at least about 97% identity to any of the SEQ ID NOs: 215-222. In some embodiments, the modified nuclease system comprises an endonuclease comprising a sequence with at least about 98% identity to any of the SEQ ID NOs: 139-146 and 303 and a modified polynucleotide comprising a sequence. Petition 870250090553, dated 03 / 10 / 2025, page 86 / 262 83 / 251 with at least about 98% identity to any of the SEQ ID NOs: 215-222. In some embodiments, the modified nuclease system comprises an endonuclease comprising a sequence with at least about 99% identity to any of the SEQ ID NOs: 139-146 and 303 and a modified polynucleotide comprising a sequence with at least about 99% identity to any of the SEQ ID NOs: 215-222. In some embodiments, the modified nuclease system comprises an endonuclease comprising 100% identity to any of the SEQ ID NOs: 139-146 and 303 and a modified polynucleotide comprising 100% identity to any of the SEQ ID NOs: 215-222.

[0144] In some embodiments, the modified nuclease system comprises an endonuclease comprising a sequence with at least about 70% identity to any of the SEQ ID NOs: 7-11 and a modified polynucleotide comprising a sequence with at least about 70% identity to SEQ ID NO: 52. In some embodiments, the modified nuclease system comprises an endonuclease comprising a sequence with at least about 75% identity to any of the SEQ ID NOs: 7-11 and a modified polynucleotide comprising a sequence with at least about 75% identity to SEQ ID NO: 52. In some embodiments, the modified nuclease system comprises an endonuclease comprising a sequence with at least about 80% identity to any of the SEQ ID NOs: 7-11 and a modified polynucleotide comprising a sequence with at least about 80% identity to SEQ ID NO: 52. Petition 870250090553, dated 03 / 10 / 2025, p. 87 / 262 84 / 251 In some embodiments, the modified nuclease system comprises an endonuclease comprising a sequence with at least about 85% identity to any of the SEQ IDs NOs: 7-11 and a modified polynucleotide comprising a sequence with at least about 85% identity to SEQ ID NO: 52. In some embodiments, the modified nuclease system comprises an endonuclease comprising a sequence with at least about 90% identity to any of the SEQ IDs NOs: 7-11 and a modified polynucleotide comprising a sequence with at least about 90% identity to SEQ ID NO: 52. In some embodiments, the modified nuclease system comprises an endonuclease comprising a sequence with at least about 95% identity to any of the SEQ IDs NOs: 7-11 and a modified polynucleotide comprising a sequence with at least about 95% identity to SEQ ID NO: 52.In some embodiments, the modified nuclease system comprises an endonuclease comprising a sequence with at least about 96% identity to any of the SEQ IDs NOs: 7-11 and a modified polynucleotide comprising a sequence with at least about 96% identity to SEQ ID NO: 52. In some embodiments, the modified nuclease system comprises an endonuclease comprising a sequence with at least about 97% identity to any of the SEQ IDs NOs: 7-11 and a modified polynucleotide comprising a sequence with at least about 97% identity to SEQ ID NO: 52. In some embodiments, the modified nuclease system comprises an endonuclease comprising a sequence with at least about 98% identity to SEQ ID NO: 52. Petition 870250090553, dated 03 / 10 / 2025, page 88 / 262 85 / 251 identity with any of the SEQ IDs NOs: 7-11 and a modified polynucleotide comprising a sequence with at least about 98% identity with SEQ ID NO: 52. In some embodiments, the modified nuclease system comprises an endonuclease comprising a sequence with at least about 99% identity with any of the SEQ IDs NOs: 7-11 and a modified polynucleotide comprising a sequence with at least about 99% identity with SEQ ID NO: 52. In some embodiments, the modified nuclease system comprises an endonuclease comprising 100% identity with any of the SEQ IDs NOs: 7-11 and a modified polynucleotide comprising 100% identity with SEQ ID NO: 52.

[0145] In some embodiments, the modified nuclease system comprises an endonuclease comprising a sequence with at least about 70% identity to any of the SEQ ID NOs: 105-109 and a modified polynucleotide comprising a sequence with at least about 70% identity to any of the SEQ ID NOs: 147-151. In some embodiments, the modified nuclease system comprises an endonuclease comprising a sequence with at least about 75% identity to any of the SEQ ID NOs: 105-109 and a modified polynucleotide comprising a sequence with at least about 75% identity to any of the SEQ ID NOs: 147-151. In some embodiments, the modified nuclease system comprises an endonuclease comprising a sequence with at least about 80% identity to any of the SEQ IDs NOS: 105-109 and a modified polynucleotide comprising a sequence with Petition 870250090553, dated 03 / 10 / 2025, p. 89 / 262 86 / 251 at least about 80% identity with any of the SEQ ID NOs: 147-151. In some embodiments, the modified nuclease system comprises an endonuclease comprising a sequence with at least about 85% identity with any of the SEQ ID NOs: 105-109 and a modified polynucleotide comprising a sequence with at least about 85% identity with any of the SEQ ID NOs: 147-151. In some embodiments, the modified nuclease system comprises an endonuclease comprising a sequence with at least about 90% identity with any of the SEQ ID NOs: 105-109 and a modified polynucleotide comprising a sequence with at least about 90% identity with any of the SEQ ID NOs: 147-151.In some embodiments, the modified nuclease system comprises an endonuclease comprising a sequence with at least about 95% identity to any of the SEQ ID NOs: 105-109 and a modified polynucleotide comprising a sequence with at least about 95% identity to any of the SEQ ID NOs: 147-151. In some embodiments, the modified nuclease system comprises an endonuclease comprising a sequence with at least about 96% identity to any of the SEQ ID NOs: 105-109 and a modified polynucleotide comprising a sequence with at least about 96% identity to any of the SEQ ID NOs: 147-151. In some embodiments, the modified nuclease system comprises an endonuclease comprising a sequence with at least about 97% identity to any of the SEQ IDs 105-109 and a modified polynucleotide comprising a sequence with... Petition 870250090553, dated 03 / 10 / 2025, p. 90 / 262 87 / 251 at least about 97% identity with any of the SEQ ID NOs: 147-151. In some embodiments, the modified nuclease system comprises an endonuclease comprising a sequence with at least about 98% identity with any of the SEQ ID NOs: 105-109 and a modified polynucleotide comprising a sequence with at least about 98% identity with any of the SEQ ID NOs: 147-151. In some embodiments, the modified nuclease system comprises an endonuclease comprising a sequence with at least about 99% identity with any of the SEQ ID NOs: 105-109 and a modified polynucleotide comprising a sequence with at least about 99% identity with any of the SEQ ID NOs: 147-151.In some embodiments, the modified nuclease system comprises an endonuclease comprising 100% identity with any of the SEQ ID NOs: 105-109 and a modified polynucleotide comprising 100% identity with any of the SEQ ID NOs: 147-151.

[0146] In some embodiments, the modified nuclease system comprises an endonuclease comprising a sequence with at least about 70% identity to any of the SEQ ID NOs: 110-116 and a modified polynucleotide comprising a sequence with at least about 70% identity to any of the SEQ ID NOs: 157-163. In some embodiments, the modified nuclease system comprises an endonuclease comprising a sequence with at least about 75% identity to any of the SEQ ID NOs: 110-116 and a modified polynucleotide comprising a sequence with at least about 75% identity to any of the Petition 870250090553, dated 03 / 10 / 2025, p. 91 / 262 88 / 251 SEQ ID Nos: 157-163. In some embodiments, the modified nuclease system comprises an endonuclease comprising a sequence with at least about 80% identity to any of the SEQ ID Nos: 110-116 and a modified polynucleotide comprising a sequence with at least about 80% identity to any of the SEQ ID Nos: 157-163. In some embodiments, the modified nuclease system comprises an endonuclease comprising a sequence with at least about 85% identity to any of the SEQ ID Nos: 110-116 and a modified polynucleotide comprising a sequence with at least about 85% identity to any of the SEQ ID Nos: 157-163.In some embodiments, the modified nuclease system comprises an endonuclease comprising a sequence with at least about 90% identity to any of the SEQ ID NOs: 110-116 and a modified polynucleotide comprising a sequence with at least about 90% identity to any of the SEQ ID NOs: 157-163. In some embodiments, the modified nuclease system comprises an endonuclease comprising a sequence with at least about 95% identity to any of the SEQ ID NOs: 110-116 and a modified polynucleotide comprising a sequence with at least about 95% identity to any of the SEQ ID NOs: 157-163. In some embodiments, the modified nuclease system comprises an endonuclease comprising a sequence with at least about 96% identity to any of the SEQ ID NOs: 110-116 and a modified polynucleotide comprising a sequence with at least about 96% identity to any of the... Petition 870250090553, dated 03 / 10 / 2025, p. 92 / 262 89 / 251 SEQ ID Nos: 157-163. In some embodiments, the modified nuclease system comprises an endonuclease comprising a sequence with at least about 97% identity to any of the SEQ ID Nos: 110-116 and a modified polynucleotide comprising a sequence with at least about 97% identity to any of the SEQ ID Nos: 157-163. In some embodiments, the modified nuclease system comprises an endonuclease comprising a sequence with at least about 98% identity to any of the SEQ ID Nos: 110-116 and a modified polynucleotide comprising a sequence with at least about 98% identity to any of the SEQ ID Nos: 157-163.In some embodiments, the modified nuclease system comprises an endonuclease comprising a sequence with at least about 99% identity to any of the SEQ ID NOs: 110-116 and a modified polynucleotide comprising a sequence with at least about 99% identity to any of the SEQ ID NOs: 157-163. In some embodiments, the modified nuclease system comprises an endonuclease comprising 100% identity to any of the SEQ ID NOs: 110-116 and a modified polynucleotide comprising 100% identity to any of the SEQ ID NOs: 157-163.

[0147] In some embodiments, the modified nuclease system comprises an endonuclease comprising a sequence with at least about 70% identity to any of the SEQ ID NOs: 117-138 and a modified polynucleotide comprising a sequence with at least about 70% identity to any of the SEQ ID NOs: 171-192. In some embodiments, the system of Petition 870250090553, dated 03 / 10 / 2025, p. 93 / 262 The modified nuclease 90 / 251 comprises an endonuclease comprising a sequence with at least about 75% identity to any of the SEQ ID NOs: 117-138 and a modified polynucleotide comprising a sequence with at least about 75% identity to any of the SEQ ID NOs: 171-192. In some embodiments, the modified nuclease system comprises an endonuclease comprising a sequence with at least about 80% identity to any of the SEQ ID NOs: 117-138 and a modified polynucleotide comprising a sequence with at least about 80% identity to any of the SEQ ID NOs: 171-192. In some embodiments, the modified nuclease system comprises an endonuclease comprising a sequence with at least about 85% identity to any of the SEQ ID NOs: 117-138 and a modified polynucleotide comprising a sequence with at least about 85% identity to any of the SEQ ID NOs: 171-192.In some embodiments, the modified nuclease system comprises an endonuclease comprising a sequence with at least about 90% identity to any of the SEQ ID NOs: 117-138 and a modified polynucleotide comprising a sequence with at least about 90% identity to any of the SEQ ID NOs: 171-192. In some embodiments, the modified nuclease system comprises an endonuclease comprising a sequence with at least about 95% identity to any of the SEQ ID NOs: 117-138 and a modified polynucleotide comprising a sequence with at least about 95% identity to any of the SEQ ID NOs: 171-192. In some embodiments, the system of... Petition 870250090553, dated 03 / 10 / 2025, page 94 / 262 The modified nuclease 91 / 251 comprises an endonuclease comprising a sequence with at least about 96% identity to any of the SEQ ID NOs: 117-138 and a modified polynucleotide comprising a sequence with at least about 96% identity to any of the SEQ ID NOs: 171-192. In some embodiments, the modified nuclease system comprises an endonuclease comprising a sequence with at least about 97% identity to any of the SEQ ID NOs: 117-138 and a modified polynucleotide comprising a sequence with at least about 97% identity to any of the SEQ ID NOs: 171-192. In some embodiments, the modified nuclease system comprises an endonuclease comprising a sequence with at least about 98% identity to any of the SEQ ID NOs: 117-138 and a modified polynucleotide comprising a sequence with at least about 98% identity to any of the SEQ ID NOs: 171-192.In some embodiments, the modified nuclease system comprises an endonuclease comprising a sequence with at least about 99% identity to any of the SEQ ID NOs: 117-138 and a modified polynucleotide comprising a sequence with at least about 99% identity to any of the SEQ ID NOs: 171-192. In some embodiments, the modified nuclease system comprises an endonuclease comprising 100% identity to any of the SEQ ID NOs: 117-138 and a modified polynucleotide comprising... 100% match with any of the following SEQ IDs: 171-192. Cells

[0148] It is described in this document, in certain Petition 870250090553, dated 03 / 10 / 2025, page 95 / 262 92 / 251 modalities, a cell comprising the systems described in this document.

[0149] In some embodiments, the cell is a eukaryotic cell (e.g., a plant cell, an animal cell, a protist cell, or a fungal cell), a mammalian cell (a Chinese hamster ovary cell (CHO), baby hamster kidney cell (BHK), human embryonic kidney cell (HEK), mouse myeloma cell (NS0), or human retinal cells), an immortalized cell (e.g., a HeLa cell, a COS cell, a HEK-293T cell, a cell MDCK, a 3T3 cell, a PC12 cell, a Huh7 cell, a HepG2 cell, a K562 cell, an N2a cell, or a cell SY5Y), an insect cell (e.g., a Spodoptera frugiperda cell, a Trichoplusia ni cell, a A Drosophila melanogaster cell, an S2 cell, or a Heliothis virescens cell), a yeast cell (e.g., a Saccharomyces cerevisiae cell, a Cryptococcus cell, or a Candida cell), a plant cell (e.g., a parenchyma cell, a collenchyma cell, or a sclerenchyma cell), a fungal cell (e.g., a Saccharomyces cerevisiae cell, a Cryptococcus cell, or a Candida cell), or a prokaryotic cell (e.g., an E. coli cell, a Streptococcus bacterium cell, a Streptomyces soil bacterium cell, or an Archaea cell). In some embodiments, the cell is a eukaryotic cell. In some embodiments, the cell is a mammalian cell. In some embodiments, the cell is an immortalized cell. In some embodiments, the cell is an insect cell. In some embodiments, the cell is a yeast cell. Petition 870250090553, dated 03 / 10 / 2025, page 96 / 262 93 / 251 In some modalities, the cell is a plant cell. In some modalities, the cell is a fungal cell. In some modalities, the cell is a prokaryotic cell.

[0150] In some embodiments, the cell is A549, HEK-293, HEK-293T, BHK, CHO, HeLa, MRC5, Sf9, Cos-1, Cos-7, Vero, BSC 1, BSC 40, BMT 10, WI38, HeLa, Saos, C2C12, cell L, HT1080, HepG2, Huh7, K562, a primary cell or a derivative thereof. Distribution and Vectors

[0151] Nucleic acid sequences encoding a modified nuclease system disclosed in this document are disclosed in some forms.

[0152] In some embodiments, the nucleic acid encoding the modified nuclease system is DNA, for example, linear DNA, plasmid DNA, or minicircle DNA. In some embodiments, the nucleic acid encoding the modified nuclease system is RNA, for example, mRNA.

[0153] In some embodiments, the nucleic acid encoding the modified nuclease system is delivered by a nucleic acid-based vector. In some embodiments, the nucleic acid-based vector is a plasmid (e.g., circular DNA molecules that can replicate autonomously within a cell), cosmid (e.g., pWE or sCos vectors), artificial chromosome, human artificial chromosome (HAC), yeast artificial chromosome (YAC), bacterial artificial chromosome (BAC), P1-derived artificial chromosome (PAC), phagemid, phage-derived, bacmid, or virus. In some embodiments, the nucleic acid-based vector is selected from the list consisting of: pSF-CMVPetition 870250090553, 03 / 10 / 2025, p. 97 / 262 94 / 251 NEO-NH2-PPT-3XFLAG, pSF-CMV-NEO-COOH-3XFLAG, pSF-CMV-PURONH2-GST-TEV, pSF-OXB20-COOH-TEV-FLAG(R)-6His, pCEP4 pDEST27, pSF-CMV-Ub-KrYFP, pSF-CMV-FMDV-daGFP, pEF1amCherry-N1 vector, pEF1a-tdTomato vector, pSF-CMV-FMDVHygro, pSF-CMV-PGK-Puro, pMCP-tag(m), pSF-CMV-PURO-NH2CMYC, pSF-OXB20-BetaGal, pSF-OXB20-Fluc, pSF-OXB20, pSF-Tac, pRI 101-AN DNA, pCambia2301, pTYB21, pKLAC2, pAc5.1 / V5-His A and pDEST8.

[0154] In some embodiments, the nucleic acid-based vector comprises a promoter. In some embodiments, the promoter is selected from the group consisting of a minipromoter, an inducible promoter, a constitutive promoter, and their derivatives. In some embodiments, the promoter is selected from the group consisting of CMV, CBA, EF1a, CAG, PGK, TRE, U6, UAS, T7, Sp6, lac, araBad, trp, Ptac, p5, p19, p40, Synapsin, CaMKII, GRK1 and their derivatives. In some modes, the promoter is a U6 promoter. In some modes, the promoter is a CAG promoter. In some modes, the promoter is encoded by a sequence of any of the SEQ ID Nos: 190-191, or a sequence having at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99% Petition 870250090553, dated 03 / 10 / 2025, p. 98 / 262 95 / 251 identity of any of the SEQ ID Nos: 190-191.

[0155] In some embodiments, the nucleic acid-based vector is a virus. In some embodiments, the virus is an alphavirus, a parvovirus, an adenovirus, an AAV, a baculovirus, a Dengue virus, a lentivirus, a herpesvirus, a poxvirus, an annelvirus, a bocavirus, a vaccinia virus, or a retrovirus. In some embodiments, the virus is an alphavirus. In some embodiments, the virus is a parvovirus. In some embodiments, the virus is an adenovirus. In some embodiments, the virus is an AAV. In some embodiments, the virus is a baculovirus. In some embodiments, the virus is a Dengue virus. In some embodiments, the virus is a lentivirus. In some embodiments, the virus is a herpesvirus. In some embodiments, the virus is a poxvirus. In some embodiments, the virus is an annelvirus. In some embodiments, the virus is a bocavirus. In some forms, the virus is a vaccinia virus. In some forms, the virus is a retrovirus.

[0156] In some embodiments, the AAV is AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAV10, AAV11, AAV12, AAV13, AAV14, AAV15, AAV16, AAV-rh8, AAV-rh10, AAV-rh12, AAV AAV-rh39, AAV-rh74, AAV-rhM4-1, AAV-hu37, AAV-Anc80, AAV-Anc80L65, AAV-7m8, AAV-PHP-B, AAV-PHP-EB, AAV-2.5, AAV2tYF, AAV-3B, AAV-2.5, AAV2tYF, AAV-3B, AAV-KHS-12, ALAV-HSC, ALAV-HSC AAV-HSC3, AAVHSC4, AAV-HSC5, AAV-HSC6, AAV-HSC7, AAV-HSC8, AAV-HSC9, AAVHSC10, AAV-HSC11, AAV-HSC12, AAV-HSC13, AAV-HSC14, AAVHSC15, AAV-HSC13, AAV-HSC14, AAVHSC15, AAV-TTT / 8, AAV-JJM, AAV-Myo AAV-NP40, AAV-NP59, AAVNP22, AAV-NP66, AAV-HSC16, or a derivative thereof. In some embodiments, the herpesvirus is HSV type 1, HSV-2, VZV, EBV, CMV, HHV-6, HHV-7 or HHV-8. Petition 870250090553, of 03 / 10 / 2025, p. 99 / 262 96 / 251

[0157] In some embodiments, the virus is AAV1 or a derivative thereof. In some embodiments, the virus is AAV2 or a derivative thereof. In some embodiments, the virus is AAV3 or a derivative thereof. In some embodiments, the virus is AAV4 or a derivative thereof. In some embodiments, the virus is AAV5 or a derivative thereof. In some embodiments, the virus is AAV6 or a derivative thereof. In some embodiments, the virus is AAV7 or a derivative thereof. In some embodiments, the virus is AAV8 or a derivative thereof. In some embodiments, the virus is AAV9 or a derivative thereof. In some embodiments, the virus is AAV10 or a derivative thereof. In some embodiments, the virus is AAV11 or a derivative thereof. In some embodiments, the virus is AAV12 or a derivative thereof. In some embodiments, the virus is AAV13 or a derivative thereof. In some embodiments, the virus is AAV14 or a derivative thereof. In some strains, the virus is AAV15 or a derivative thereof. In some strains, the virus is AAV16 or a derivative thereof.In some embodiments, the virus is AAV rh8 or a derivative thereof. In some embodiments, the virus is AAV-rh10 or a derivative thereof. In some embodiments, the virus is AAV-rh20 or a derivative thereof. In some embodiments, the virus is AAV-rh39 or a derivative thereof. In some embodiments, the virus is AAV-rh74 or a derivative thereof. In some embodiments, the virus is AAV-rhM4-1 or a derivative thereof. In some embodiments, the virus is AAV-hu37 or a derivative thereof. In some embodiments, the virus is AAV-Anc80 or a derivative thereof. In some embodiments, the virus is AAVAnc80L65 or a derivative thereof. In some embodiments, the virus is AAV-7m8 or a derivative thereof. In some embodiments, the virus is AAV-PHP-B or a derivative thereof. In some embodiments, the virus is AAV-PHP-EB or a derivative thereof. Petition 870250090553, dated 03 / 10 / 2025, p. 100 / 262 97 / 251 In some embodiments, the virus is AAV-2.5 or a derivative thereof. In some embodiments, the virus is AAV-2tYF or a derivative thereof. In some embodiments, the virus is AAV-3B or a derivative thereof. In some embodiments, the virus is AAV-LK03 or a derivative thereof. In some embodiments, the virus is AAVHSC1 or a derivative thereof. In some embodiments, the virus is AAV-HSC2 or a derivative thereof. In some embodiments, the virus is AAV-HSC3 or a derivative thereof. In some embodiments, the virus is AAV-HSC4 or a derivative thereof. In some embodiments, the virus is AAV-HSC5 or a derivative thereof. In some embodiments, the virus is AAV-HSC6 or a derivative thereof. In some embodiments, the virus is AAV-HSC7 or a derivative thereof. In some embodiments, the virus is AAV-HSC8 or a derivative thereof. In some forms, the virus is AAV-HSC9 or a derivative thereof. In some forms, the virus is AAV-HSC10 or a derivative thereof. In some forms, the virus is AAV-HSC11 or a derivative thereof.In some embodiments, the virus is AAV-HSC12 or a derivative thereof. In some embodiments, the virus is AAV-HSC13 or a derivative thereof. In some embodiments, the virus is AAV-HSC14 or a derivative thereof. In some embodiments, the virus is AAV-HSC15 or a derivative thereof. In some embodiments, the virus is AAVTT or a derivative thereof. In some embodiments, the virus is AAV-DJ / 8 or a derivative thereof. In some embodiments, the virus is AAV-Myo or a derivative thereof. In some embodiments, the virus is AAV-NP40 or a derivative thereof. In some embodiments, the virus is AAV-NP59 or a derivative thereof. In some embodiments, the virus is AAV-NP22 or a derivative thereof. In some embodiments, the virus is AAV-NP66 or a derivative thereof. In some embodiments, the virus is AAV-HSC16 or a derivative thereof. Petition 870250090553, dated 03 / 10 / 2025, p. 101 / 262 98 / 251 derived from this.

[0158] In some embodiments, the virus is HSV-1 or a derivative thereof. In some embodiments, the virus is HSV-2 or a derivative thereof. In some embodiments, the virus is VZV or a derivative thereof. In some embodiments, the virus is EBV or a derivative thereof. In some embodiments, the virus is CMV or a derivative thereof. In some embodiments, the virus is HHV-6 or a derivative thereof. In some embodiments, the virus is HHV-7 or a derivative thereof. In some embodiments, the virus is HHV-8 or a derivative thereof.

[0159] In some embodiments, the nucleic acid encoding the modified nuclease system is distributed by a non-nucleic acid-based delivery system (e.g., a non-viral delivery system). In some embodiments, the non-viral delivery system is a liposome. In some embodiments, the nucleic acid is associated with a lipid. The lipid-associated nucleic acid, in some embodiments, is encapsulated in the aqueous interior of a liposome, intercalated within the lipid bilayer of a liposome, linked to a liposome through a linker molecule that is associated with both the liposome and the nucleic acid, trapped in a liposome, complexed with a liposome, dispersed in a solution containing a lipid, mixed with a lipid, combined with a lipid, contained as a suspension in a lipid, contained or complexed with a micelle, or otherwise associated with a lipid.In some embodiments, the nucleic acid is contained within a lipid nanoparticle (LNP).

[0160] In some embodiments, the fusion protein or genome editing system is introduced into the cell of Petition 870250090553, dated 03 / 10 / 2025, p. 102 / 262 99 / 251 any suitable form, in a stable or transient manner. In some embodiments, a fusion protein or genome editing system is transfected into the cell. In some embodiments, the cell is transduced or transfected with a nucleic acid construct encoding a fusion protein or genome editing system. For example, a cell is transduced (e.g., with a virus encoding a fusion protein or genome editing system) or transfected (e.g., with a plasmid encoding a fusion protein or genome editing system) with a nucleic acid encoding a fusion protein or genome editing system, or the translated fusion protein or genome editing system. In some embodiments, transduction is either stable or transient.In some embodiments, cells expressing a fusion protein or genome editing system, or containing a fusion protein or genome editing system, are transduced or transfected with one or more gRNA molecules, for example, when the fusion protein or genome editing system comprises a CRISPR nuclease. In some embodiments, a plasmid expressing a fusion protein or genome editing system is introduced into cells via electroporation, transient (e.g., lipofection) and stable genome integration (e.g., piggybac), and viral transduction (e.g., lentivirus or AAV), or other methods known to those skilled in the art. In some embodiments, the gene editing system is introduced into the cell as one or more polypeptides. In some embodiments, delivery is achieved through the use of RNP complexes. The methods. Petition 870250090553, dated 03 / 10 / 2025, page 103 / 262 100 / 251 delivery methods for polypeptides and / or RNPs to cells are known in the art, for example, by electroporation or cell compression.

[0161] Exemplary methods of nucleic acid delivery include lipofection, nucleofection, electroporation, stable genome integration (e.g., piggybac), microinjection, biolistics, virosomes, liposomes, immunoliposomes, polycation or lipid nucleic acid conjugates, nude DNA, artificial virions, and DNA uptake by potentiated agents. Lipofection is described, for example, in U.S. Pat. Nos. 5,049,386; 4,946,787; and 4,897,355) and lipofection reagents are commercially available (e.g., Transfectam™, Lipofectin™, and SF Cell Line 4D-Nucleofector X Kit™ (Lonza)). Cationic and neutral lipids that are suitable for efficient lipofection of receptor-recognition polynucleotides include those of WO 91 / 17424 and WO 91 / 16024. In some embodiments, delivery is to target cells (e.g., in vitro or ex vivo administration) or tissues (e.g., in vivo administration).In some embodiments, the nucleic acid is contained within a liposome or nanoparticle that specifically targets a host cell.

[0162] Additional methods for delivering nucleic acids to cells are known to those skilled in the art. See, for example, US 2003 / 0087817. Methods of Use

[0163] Methods for modifying a target nucleic acid comprising providing a modified nuclease system are described in this document in certain embodiments. Petition 870250090553, dated 03 / 10 / 2025, page 104 / 262 101 / 251 disclosed in this document. In some embodiments, the modified nuclease system comprises an endonuclease and a modified guide polynucleotide. In some embodiments, the target nucleic acid is double-stranded. In some embodiments, the target nucleic acid is double-stranded DNA. In some embodiments, the target nucleic acid is single-stranded.

[0164] In some embodiments, the methods are used to introduce a modification into the genome of a cell. In some embodiments, the modification is an insertion, deletion, or mutation. In some embodiments, the methods are used to introduce site-targeted insertions, deletions, and / or mutations in the genome of a cell (e.g., an insertion and a mutation). In some embodiments, the methods are used in combination with a nucleic acid template to facilitate site-targeted insertions in the genome of a cell.

[0165] In some embodiments, the cell is a human cell. In some embodiments, the cell genome or a vector contained within the cell is modified. In some embodiments, the cell genome is modified ex vivo. In some embodiments, the cell genome is modified in vivo.

[0166] In some embodiments, the modified guide polynucleotide targets a gene in a cell. In some embodiments, the modified guide polynucleotide targets a gene in a mammalian cell. In some embodiments, the mammalian cell is a pig, a cow, a goat, a sheep, a rodent, a rat, a mouse, a non-human primate, or a human cell.

[0167] In some modalities, the target gene is HAO1. In some modalities, the gRNA comprises a sequence with Petition 870250090553, dated 03 / 10 / 2025, p. 105 / 262 102 / 251 at least approximately 20%, at least approximately 25%, at least approximately 30%, at least approximately 35%, at least approximately 40%, at least approximately 45%, at least approximately 50%, at least approximately 55%, at least approximately 60%, at least approximately 65%, at least approximately 70%, at least approximately 75%, at least approximately 80%, at least approximately 85%, at least approximately 90%, at least approximately 91%, at least approximately 92%, at least approximately 93%, at least approximately 94%, at least approximately 95%, at least approximately 96%, at least approximately 97%, at least approximately 98%, or at least approximately 99% identity with any of the SEQ ID Nos: 251260 and 271-274. In some embodiments, the gRNA comprises a sequence with at least about 70% identity to either of the SEQ ID NOs: 251-260 and 271-274. In some embodiments, the gRNA comprises a sequence with at least about 75% identity to either of the SEQ ID NOs: 251-260 and 271-274.In some embodiments, the gRNA comprises a sequence with at least approximately 80% identity to either of the SEQ ID NOs: 251-260 and 271-274. In some embodiments, the gRNA comprises a sequence with at least approximately 85% identity to either of the SEQ ID NOs: 251-260 and 271-274. In some embodiments, the gRNA comprises a sequence with at least approximately 90% identity to either of the SEQ ID NOs: 251-260 and 271-274. In some embodiments, the gRNA comprises a sequence with at least approximately 91% identity to either of the SEQ ID NOs: 251-260 and 271-274. In some embodiments, the gRNA comprises a sequence with at least approximately 92% identity to any of the SEQ ID Nos: 251-260 and 271-274. In some embodiments, the gRNA comprises a sequence with at least... Petition 870250090553, dated 03 / 10 / 2025, p. 106 / 262 103 / 251 approximately 93% identity with any of the SEQ ID NOs: 251-260 and 271-274. In some embodiments, the gRNA comprises a sequence with at least approximately 94% identity with any of the SEQ ID NOs: 251-260 and 271-274. In some embodiments, the gRNA comprises a sequence with at least approximately 95% identity with any of the SEQ ID NOs: 251-260 and 271-274. In some embodiments, the gRNA comprises a sequence with at least approximately 96% identity with any of the SEQ ID NOs: 251-260 and 271-274. In some embodiments, the gRNA comprises a sequence with at least approximately 97% identity with any of the SEQ ID NOs: 251-260 and 271-274. In some embodiments, the gRNA comprises a sequence with at least approximately 98% identity to either of the SEQ ID NOs: 251-260 and 271-274. In some embodiments, the gRNA comprises a sequence with at least approximately 99% identity to either of the SEQ ID NOs: 251-260 and 271-274.In some embodiments, the gRNA comprises a sequence with 100% identity to any of the SEQ IDs 251-260 and 271-274.

[0168] In some embodiments, the gRNA hybridizes or targets a sequence complementary to an HAO1 sequence with at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least Petition 870250090553, dated 03 / 10 / 2025, p. 107 / 262 104 / 251 approximately 97%, at least approximately 98%, or at least approximately 99% identity with any of the SEQ ID NOs: 261-270 and 275-278. In some embodiments, the gRNA hybridizes or targets a sequence complementary to an HAO1 sequence with at least approximately 70% identity with any of the SEQ ID NOs: 261-270 and 275-278. In some embodiments, the gRNA hybridizes or targets a sequence complementary to an HAO1 sequence with at least approximately 75% identity to any of the SEQ ID NOs: 261-270 and 275-278. In some embodiments, the gRNA hybridizes or targets a sequence complementary to an HAO1 sequence with at least approximately 80% identity to any of the SEQ ID NOs: 261-270 and 275-278. In some embodiments, the gRNA hybridizes or targets a sequence complementary to an HAO1 sequence with at least approximately 85% identity to any of the SEQ ID NOs: 261-270 and 275-278.In some embodiments, the gRNA hybridizes or targets a sequence complementary to an HAO1 sequence with at least approximately 90% identity to any of the SEQ ID NOs: 261-270 and 275-278. In some embodiments, the gRNA hybridizes or targets a sequence complementary to an HAO1 sequence with at least approximately 91% identity to any of the SEQ ID NOs: 261-270 and 275-278. In some embodiments, the gRNA hybridizes or targets a sequence complementary to an HAO1 sequence with at least approximately 92% identity to any of the SEQ ID NOs: 261-270 and 275-278. In some embodiments, the gRNA hybridizes or targets a sequence complementary to an HAO1 sequence with at least approximately 93% identity to any of the SEQ ID NOs: 261-270 and 275-278. In some embodiments, the gRNA... Petition 870250090553, dated 03 / 10 / 2025, p. 108 / 262 105 / 251 hybridizes or targets a sequence complementary to an HAO1 sequence with at least approximately 94% identity to any of the SEQ ID NOs: 261-270 and 275-278. In some embodiments, the gRNA hybridizes or targets a sequence complementary to an HAO1 sequence with at least approximately 95% identity to any of the SEQ ID NOs: 261-270 and 275-278. In some embodiments, the gRNA hybridizes or targets a sequence complementary to an HAO1 sequence with at least approximately 96% identity to any of the SEQ ID NOs: 261-270 and 275-278. In some embodiments, the gRNA hybridizes or targets a sequence complementary to an HAO1 sequence with at least approximately 97% identity to any of the SEQ ID NOs: 261-270 and 275-278. In some embodiments, the gRNA hybridizes or targets a sequence complementary to an HAO1 sequence with at least approximately 98% identity to any of the SEQ ID NOs: 261-270 and 275-278.In some embodiments, the gRNA hybridizes or targets a sequence complementary to an HAO1 sequence with at least approximately 99% identity to any of the SEQ ID NOs: 261-270 and 275-278. In some embodiments, the gRNA hybridizes or targets a sequence complementary to an HAO1 sequence with 100% identity to any of the SEQ ID NOs: 261-270 and 275-278.

[0169] In some embodiments, the target gene is TTR. In some embodiments, the gRNA comprises a sequence with at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about Petition 870250090553, dated 03 / 10 / 2025, p. 109 / 262 106 / 251 75%, at least about 80%, at least about 85%, at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99% identity with any of the SEQ IDs NOs: 279-290. In some embodiments, the gRNA comprises a sequence with at least about 70% identity with any of the SEQ IDs NOs: 279-290. In some embodiments, the gRNA comprises a sequence with at least about 75% identity with any of the SEQ IDs NOs: 279-290. In some embodiments, the gRNA comprises a sequence with at least about 80% identity to any of the SEQ IDs NOs: 279-290. In some embodiments, the gRNA comprises a sequence with at least about 85% identity to any of the SEQ IDs NOs: 279-290.In some embodiments, the gRNA comprises a sequence with at least approximately 90% identity to any of the SEQ IDs NOs: 279-290. In some embodiments, the gRNA comprises a sequence with at least approximately 91% identity to any of the SEQ IDs NOs: 279-290. In some embodiments, the gRNA comprises a sequence with at least approximately 92% identity to any of the SEQ IDs NOs: 279-290. In some embodiments, the gRNA comprises a sequence with at least approximately 93% identity to any of the SEQ IDs NOs: 279-290. In some embodiments, the gRNA comprises a sequence with at least approximately 94% identity to any of the SEQ IDs NOs: 279-290. In some embodiments, the gRNA comprises a sequence with at least approximately 95% identity to any of the SEQ IDs NOs: 279-290. Petition 870250090553, dated 03 / 10 / 2025, p. 110 / 262 107 / 251 identity with any of the SEQ IDs NOs: 279-290. In some embodiments, the gRNA comprises a sequence with at least approximately 96% identity with any of the SEQ IDs NOs: 279-290. In some embodiments, the gRNA comprises a sequence with at least approximately 97% identity with any of the SEQ IDs NOs: 279-290. In some embodiments, the gRNA comprises a sequence with at least approximately 98% identity with any of the SEQ IDs NOs: 279-290. In some embodiments, the gRNA comprises a sequence with at least approximately 99% identity with any of the SEQ IDs NOs: 279-290. In some embodiments, the gRNA comprises a sequence with 100% identity with any of the SEQ IDs NOs: 279-290.

[0170] In some embodiments, the gRNA hybridizes or targets a sequence complementary to a TTR sequence with at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99% identity with any of the SEQ IDs NOs: 291-302. In some embodiments, the gRNA hybridizes or targets a sequence complementary to a TTR sequence with at least approximately 70% identity with any of the SEQ IDs NOs: 291-302.In some forms, the gRNA hybridizes or... Petition 870250090553, dated 03 / 10 / 2025, p. 111 / 262 108 / 251 targets a sequence complementary to a TTR sequence with at least approximately 75% identity to any of the SEQ ID NOs: 291-302. In some embodiments, the gRNA hybridizes or targets a sequence complementary to a TTR sequence with at least approximately 80% identity to any of the SEQ ID NOs: 291-302. In some embodiments, the gRNA hybridizes or targets a sequence complementary to a TTR sequence with at least approximately 85% identity to any of the SEQ ID NOs: 291-302. In some embodiments, the gRNA hybridizes or targets a sequence complementary to a TTR sequence with at least approximately 90% identity to any of the SEQ ID NOs: 291-302. In some embodiments, the gRNA hybridizes or targets a sequence complementary to a TTR sequence with at least approximately 91% identity to any of the SEQ IDs NOS: 291-302.In some embodiments, the gRNA hybridizes or targets a sequence complementary to a TTR sequence with at least approximately 92% identity to any of the SEQ ID NOs: 291-302. In some embodiments, the gRNA hybridizes or targets a sequence complementary to a TTR sequence with at least approximately 93% identity to any of the SEQ ID NOs: 291-302. In some embodiments, the gRNA hybridizes or targets a sequence complementary to a TTR sequence with at least approximately 94% identity to any of the SEQ ID NOs: 291-302. In some embodiments, the gRNA hybridizes or targets a sequence complementary to a TTR sequence with at least approximately 95% identity to any of the SEQ ID NOs: 291-302. In some embodiments, the gRNA hybridizes or targets a sequence complementary to a TTR sequence with at least... Petition 870250090553, dated 03 / 10 / 2025, p. 112 / 262 109 / 251 approximately 96% identity with any of the SEQ ID NOs: 291-302. In some embodiments, the gRNA hybridizes or targets a sequence complementary to a TTR sequence with at least approximately 97% identity with any of the SEQ ID NOs: 291-302. In some embodiments, the gRNA hybridizes or targets a sequence complementary to a TTR sequence with at least approximately 98% identity with any of the SEQ ID NOs: 291-302. In some embodiments, the gRNA hybridizes or targets a sequence complementary to a TTR sequence with at least approximately 99% identity with any of the SEQ ID NOs: 291-302. In some embodiments, the gRNA hybridizes or targets a sequence complementary to a TTR sequence with 100% identity to any of the SEQ IDs 291-302. EXAMPLES Example 1 - In silico identification of effectors Type II CRISPR

[0171] Putative type II CRISPR effectors were identified. The resulting homologs were filtered to include those with an e value < 1 x 10-5, a length > 500 aa, and associated CRISPR loci predicted using minCED. The effectors were dereplicated to 99% amino acid identity (AAI), globally aligned, and a phylogenetic tree was constructed.

[0172] Type II effectors were identified from families MG171, MG177, MG183 and MG21 (SEQ ID NOs: 105-146). All type II effectors have the catalytic residues necessary for activity and vary in length between 1,064 and 1,154 aa. Example 2 - sgRNA design and in vitro activity Petition 870250090553, dated 03 / 10 / 2025, page 113 / 262 110 / 251 of MG171 and MG177 nucleases sgRNA project

[0173] TracrRNAs were determined. TracrRNAs (SEQ ID NOs: 147-151, 157-163, 171-192, and 215-222) and repeats (SEQ ID NOs: 152-156, 164-170, 193-214, and 223-230) were folded, trimmed, and connected to a GAAA tetraloop sequence, or TTCG if GAAA changed the fold to form sgRNAs. Effectors were screened with eight sgRNA designs (SEQ ID NOs: 231-250) consisting of a short and long scaffold, 40% and 67% GC content spacers, and 20 nt and 24 nt spacers. In vitro activity assay

[0174] CRISPR effector nucleases were expressed in an in vitro expression system using 5 nM of a PCR-generated DNA template. After expression, the nuclease reaction mixtures were diluted 10-fold and subjected to nuclease reactions for 1 hour in a mixture containing 5 nM of protospacer adjacent motif (PAM) library DNA plasmid and 50 nM of sgRNA in 10 mM Tris pH 7.5, 100 mM NaCl, and 10 mM MgCl2. The PAM plasmids digested in the nuclease reactions were cleaned using size-selective purification beads and eluted in TE buffer. The digested PAM plasmids (15 nM) were blunt-ended ligated to double-stranded adapter oligos (150 nM) with T4 ligase in 1X T4 ligase buffer. The bound product was sequenced using 150 bp single-read amplicon sequencing. The resulting reads were filtered for a quality score >20.PAMs were identified by mapping the reads to the key PAM plasmid structures that require a match. Petition 870250090553, dated 03 / 10 / 2025, page 114 / 262 111 / 251 perfect. SeqLogos of the PAMs were generated and PAM sequences were determined by the height of each nucleotide. The cleavage site was identified by calculating the distance between the PAM and the attached adapter.

[0175] The in vitro cleavage assay demonstrated that MG171-1, MG171-2, MG171-3, MG171-4, MG171-5, MG177-2, MG1773, MG177-4, MG177-5, and MG177-6 are active type II CRISPR effector nucleases. An exemplary PAM and the cleavage position relative to the PAM for the effector nuclease MG171-1 are shown in FIG. 1. Example 3 - In the cell editing activity of MG nucleases mRNA synthesis

[0176] Nucleic acids encoding MG21-1 or MG23-1 were cloned into pUC19 plasmids including an RNA-pol T7 promoter, 5' and 3' UTRs, and a 100 nt polyA tail. To linearize the plasmid, 100 μg of plasmid were digested with SapI. The plasmid was purified with phenol / chloroform and precipitated with 70% ethanol. The DNA pellet was resuspended in 20 μL of nuclease-free water. For in vitro transcription reactions, 1 μg of linearized plasmid DNA was added to a 20 μL reaction containing 1X reaction buffer (40 mM Tris-HCl pH 7.5, 16.5 mM MgCl2, 50 mM NaCl, 2.5 mM Epermidine, 1 mM DTT) and 750 units of Hi-T7 RNA polymerase. The reaction was incubated at 50 °C for 1 hour and the resulting transcribed mRNA was purified. Mammalian cellular activity assay

[0177] Hep3B cells were cultured in EMEM + 10% FBS at 37 °C and 5% CO2. The cells were nucleofected with MG21-1 or MG23-1 mRNA along with guide RNAs. Petition 870250090553, dated 03 / 10 / 2025, page 115 / 262 Chemically synthesized 112 / 251 guide RNAs targeting HAO1 or TTR (500 ng mRNA / 150 pmol guide RNA) were injected into Hep3B cells (100,000) using an electroporator. 72 hours after nucleofection, cells were harvested and genomic DNA extracted. PCR primers appropriate for use in NGS-based DNA sequencing were generated, optimized, and used to amplify individual target sequences for each guide RNA using high-fidelity Q5 DNA polymerase. Amplicons were sequenced and analyzed for gene editing.

[0178] Up to 97% indels were observed with MG21-1 for both HAO1 and TTR (FIGs. 2 and 3), while MG231 resulted in up to 63% indels (FIG. 4). These results demonstrate the ability of MG21-1 and MG23-1 to robustly edit genes at therapeutically relevant loci. Table 2: Sequence Listing Cat. SEQ ID NO: Description Type Organism Other Information Sequence Effectors MG5 1 Effector MG5-1 Protein unknown organism not cultured with predicted taxonomy Butyrivibrio sp. CAG:2820 MPVYLGLDIGSNSVGSAW VDTDCKEIHLAASVFPAG VDEQEDKRGAPKNQARRQ TRSQRRTIHRRAARKRTL VRFLMERGLLPRDGGELR MLFDVTPWSLRREALKQP LTPYEFGRIVVHLAQRRG ALGITADPEVAEEGESTE RGDSENKKKRDEDRKVKR GIRRLEALMKERGAETVG QLMADLMDERKRQQDGAS WNDPIRNRQYRMPEDQQL FGGRELVRKEFHRIVEVQ RGFQRSELGGMLTDKLVK DLDDPSQTGTWRHRGLLF GQRRTYWDTGTLGRCVLE PTERCVPIADRQADYFRV VETVNNIRIERRGHELAA Petition 870250090553, dated 03 / 10 / 2025, page 116 / 262 113 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence LTADERKKVIDLLRGPLG ERKHKGKLVPKTTASVTD LKRALEIKPRDKSVRLNI EADEKREINTDWFHREIV HGAFGETRWQETSEEKRE SVNRAILRFDPDQADDAK KLHEGAKRWWGLDDAAAA RLVEAWKVRPKLEKRLHL SRRAILNLLPYMEQFDSA NNRWPTQQEARKAHAKVL QERFENGGDCADQIAARR YATGALGLTAADRRFMRL DKHQITEALPELPPAPTL SNPVVRKAVHEVRRHLLA WLRKSRRKPDRVVIEFAR GVQDTAKRRNEQLAANRA REKDRKLIEENLRAWGIA QSNWDRAVLRVRLSREQG GVCPFSLTGSNANRTITE RMAAEGTDVEVEHIIPQG LTPRTMAYNNLVLCFREA NRGKGMRTPADWLGPEGV KAMLQRLDKAPIKQNHIK WERLQAPTPDEEGFRNSQ LTDTAYAARQVAAYIADA LYDGKGLPERGGQRRIFT TKGEYTSRLRADWGLHES TIDRAHGLEQPPTPDELA TDPHLEQSSRRARKEPKD RSDHRHHAIDALITALLG PELLTVVGRQAREDREYR ERTGYWPRRTAVPHPAPW PTPEAFHDAVVAAFDELV VANRPVKRRLVGAFHEEQ HYGPVFPPLPRHRTEAPD ALFTNRIPIYQSPQKRLT PNHLRVPEGWDELSAKLD DLNVPVHEKRSIRRQLAE MEDPSPGKPGIVRDRALR DCIRKCLHRNGLDPDRFK PADIKKLVAEGKLTMASG IPIKSVVLLRTNTDPVII Petition 870250090553, dated 03 / 10 / 2025, page 117 / 262 114 / 251 Cat. SEQ ID NO: Descrição Tipo Organismo Outras Informações Sequência PRKRWDPGANRMVPDDDP HAVRVYIGGNNHHIAIRE NRKTGRWSGKVVRMFEAA RRVRPAQSPDGSREGPRP AVDRSDHANARFVMSLAE GEMIYARRKDRPEELADY FVVCKIDPSGRIHLAPHW DARKAPPSDKKKRTSEHQ DRWDAVPAHLEDCGPEPG NPPYKVHVGPLGEVHRLD RD* Efet ores MG5 2 Efetor MG5-2 Protein of the ecido organism or no cultivad of com taxonomi a prevista Butyrivi brio sp. CAG:2821 MPITLGLDLGPNSIGWAL VNDEDKRLIDCGVRVFPE GVDKFDTKKEESRNESRR KARAMRRQVRRRAVRRRR LLDALISVGLFPADPVEQ QKLYERDPYELRTRALDQ QLEPHEIGRVLLQINQRR GFKSNKKEEAKAESKAKR KRHDAEKKPSVDTEKKVE DILLEMRDLERAIKDSGA RTLGEYLHLKNQTLDHTN RKDDDHVRGRHTLRNMLM EEFDRIWNNQTELYPNIL SEQLGYGKLGKGKDIQRP LPKYREFLDSNNVVKNPR YGMNDLEAFGLFGLVFFH RTLKPVPREIVGLCELEP GERRCPRADRRAQRFRLL QEVNNLRYIDPDALEERE LDKDQRALLLNHLATREK ASFDDLRKKLGFLESVKF NLERGKRSGIKGMVVDQQ MAKAIGKSWHKLSEDPKT GIVSALIGSVDDDETYEL LTKEFDLNSDQANAALGA DLPDGYLQLSLIAVNKLL PHMERGLVYEHSDPLKSA RAAAGYDDPWSLRRRVFD KLPDPARVSDCPIGDIPN PVVKRTLVELRKVVNAIL REQRRATGDPKWRPDSVH Petition 870250090553, dated 03 / 10 / 2025, p. 118 / 262 115 / 251 Cat. SEQ ID NO: Descrição Tipo Organismo Outras Informações Sequência VEMGRDVKTRPKNKKSPA YWKYVQEEEERAEREGRR NKAKEKLRENNIPYGAGG RNIIKYLLWEEQSRGCIY SGKPISFAQLFTEQVEID HILPRSQSLDDSQMNLVV CFHDENHPTMGKGQRTPR EWLEHANPAKYEAVCQRA KALPYPKYKRFFRKEAKL DEFIARQLNDARYIAKAT AEYLRCLFEHEQNKSGVV LGLKGQLTSTLRRLWGLD TILCELPDSPAWQEQNNL RPGEKNRADHRHHAIDAI VVALTDRSRLKKLAKGFE VMERVDHETGEAEYAIVY AGDDISAPWKGFRVDVVT RINDLKPPCRGVSRRAER KVAGALHDDMPFGPTSES DVYVKRKPIETLSANEVD KIRDGGIKKIVTDALSDA GIEFGRGKKPDAKEMKRV LSDLAMHSGVPIKRVRLL VPSKTVQPIREGTSYQAY VNPMSTHHLALFEWHVNG KRKRGAAFVTMLEAMKRV KKHERIIQRTPPINHQTI PPDATFLFSLSGGEMVLA QVNGQEQLLVYDTAAQTS EQMWFYLHTDARKQADKK RYSYKPNTLRARKVTVDP LGRIRWAND* Efet ores MG5 3 Efetor MG5-3 Proteína desconh ecido organism o não cultivad o com taxonomi a prevista Butyrivi MATVLGLDIGSNSVGSAW IDTDKKVIKLGCSVFPAG VEETDEKRGAPKNQARRS QRQQRRSLERRAKLKRRL RQYLIKKKWMPVEKHELA AWENLNPWLLRKAALERE LTEYEFGRILLHLAQRRG AWWFDEEQKDTEKSKKNK AAETPGTIEYTKRIMGEK GAETFGKLIAMEYEERKT Petition 870250090553, dated 03 / 10 / 2025, page 119 / 262 116 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence brio sp. CAG:2822 KTPNKKLRSDRVRNRANA FGDKESEYVADRHMIIAE FIKIWDEQSKYNGQLAKQ LTENCKKELYNKEKTNTW RCQGVLFSQRKAYWNMGT LGRCDLEPTDMKCPKADM YAQEFLVLTSVNNIRITP PAESVRKLDPQEREKVVN AVRKQKTASESTIRKALG IDKGANNTQYTLNTDGDK FTVNGDWFYSQVVCGVFG EDVWGGFGENKKDSVNSA ILKFDPNDDTDKEKFKVG CKQWWGLDDEQTEKLMAV WEKRPKKDTRVNLSRKAI KNLLPYLRDGWSVTEARD MFAEDGSSGSNDLTRKRY STKEVVVNKRIRHFQKKH PELLPPVSDGISNPVVRK SIHEVRKHLMEYPRRYGK KPDRVVIELAREARQSEK VIARRIQKNKAIDALRKE IIETHELDSPDITSTQRE AAIKRVRLCRQQRYACPY SGLNEEKDKYACAYSGKP ITEAQAVHGEGLEIDHIV PRSKGGSNGMSNLVLCYS TANQGKGKRTPIDWLSKE DFWHLELRFKHLKPQKSK AGGKTGAITKDNVDMTDK AKWENLHRKTPKEGFTEE QLCSAAYAATQTTDWINK VLYGNENKGKRHVFASNG DYTGLLRRDWGLFFDESG ERSEKGRKNRGDHRHHAV DAAVIAMTPQCFSKIKAS FIDYEEQKENKNIEPKWK TIDSPWDGFSEQLAEEYQ QLKISHRPQRRKLVLALH NDSLYGPAYNEDGIRQKS HVVKSITIGGLKPSHLRV PDGWNDLIKDIENADTTT Petition 870250090553, dated 03 / 10 / 2025, pp. 120 / 262 117 / 251 Cat. SEQ ID NO: Descrição Tipo Organismo Outras Informações Sequência EKRKIRRRMLDSPDVKPA TSGVVKDRWLREELRDCL RRNGLNPDKFSKTELKRI IEDGNLTLSSGNPIRKVR ILWSLTTTPPIKRKKYNY YKNQEGYDENRKSLRYYK PDGNHHIEIREDKKGNWK GDPVTLFDAARRVRPPKD TGLASTTAVDRTDNKDGK FIMSLCIGDTVHMAHPLK EGVVDYFVVFKFSGNRIY FTPHYSTGKAQPKDESKR KRSEIYREEIEVPVSKLK KLMVFNNSIPEKVAISPL GDIRVLVKN* Efet ores MG5 4 Efetor MG5-4 Proteína desconh ecido organism o no cultivad o com taxonomi a prevista Butyrivi brio sp. CAG:2823 MGKTVLGLDLGPTSVGGA LVDTEKYRVRCSFVRIFP EGVDRDQQGGEQSKSQAR RISRGQRRQIARRADRKR LVRLALQQMELLPEDPQE LSKILAENPYPLRAKAVH EKVAPFELGRIFFHLAVR RGFLSNRKTDKSREASEM LTEIGELQQRLDERGQTL GECLNEECENHAPEELNR PVRARHTQRSMYESEFDA IWEKQREYYPDLLTTDLK LGQNRGAEYPAEPKPLEE NNAISKQKRWAELARRHL AQFGLHGLIFFQRKMYWP RSVVGQCELTREDDPNKR CKRKRCPKADRAAQVFRI LQEVNNLRVFDDGGFRKL ADEERNTIVNALLSTKQQ TFDALRKKLKFAEHMSFN FERGGRDKLKGHETDSLL SSGKVLGKKWRQLDGEAK DAIVEICIYEEREEVAIK RLKEECGLSLEEAQRASA THLPDGYMHFCREAICRL IPYLERGLLLMANDATDS ALHAAGYLRPDQRVIDQK Petition 870250090553, dated 03 / 10 / 2025, pp. 121 / 262 118 / 251 Cat. SEQ ID NO: Descrição Tipo Organismo Outras Informações Sequência ESLPQSPDLPNPLVRQAL IEVRKAVNAIIRDHGKPD RIHIELAREAKKSFEERR EIRFENTKRQKLREKIGD RLVEEFGIKPTRNNVNRY LLWQEQEGDCLYCGKNIS PTQLFNGDADIDHILPRW RSLDDSLGNKVICHRRCN EEKKDRTPAEWLKESDRP RFDRMIQLARKLDHGKRQ RLEQMDIQLDHFVERQLR DTTYIATCVKEYLECLGV PIICPRGGMTKDLRHWWG MNNILDPEKRGRKNRADH RHHAIDAIVIALTDYARL HALANARGENMPPPWPGF LNDARMSVLSVNVSHRAQ RRISGALHEATFYGPTKK LWRQAAEDSPRPWAKNWI EDESVYVRRKSVDSIENA KHLAKVRDETIREILRQH LQDQGIDPDGKKKYPKDA FKGENLPRMPNKKNPGRP GVPIKKVRMLEESETFRA VSERRDFQRVKPGNNHHV IYWAQGEGEDEKWSADVI TMWDAARRARAGLPSVDT TPPRGKRFVMSLSLGEMF EMVGDDGEIKLCVVRKMD QRSKRVYYKVHTDARETD LVNKDNLYLSPKKMQERS ARKVTVDPLGRIRWAND* Efet ores MG5 5 Efetor MG5-5 Protein of the ecido organism or no cultivad of com taxonomi a prevista Butyrivi MQTLGLDVGSNSVGSAWI DSSTGDVTTGTSIFPAGV DEQDDKRGEPKNAKRRMT RRTRITLARRSQRKRELR ARLVDVGLLPPDEGRFRK LLDETDPWRLRRRGLDEE LTPHEFGRVLLHLAQRRG ALGLKLADPEGSDDTASG EDGEVKAAIGRVRAKMLQ RGARTFGEFISMVRDEGV Petition 870250090553, dated 03 / 10 / 2025, pp. 122 / 262 119 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence brio sp. CAG:2824 TAITTEDRRKRKNGPRIF RDPVRNKAHSYEHCADRD MIRHEFSTLWDKQKQLGG KTAGILTDDHDLRRTLDD DRGDAVWRHKGLLFGQRR QTWDLGTLGRCVLEPTDR CAPHADMYGSRYLVVETI NNLKIIERGKVARPLTSE ERERIRGYLSGPLGEIKS GKRKGEPKTTVSVTDLRN LMGTAKEGWGRASKSSLF RFNIETDEDRTINTDWFS REIIHGAISPGTWDSMSE RLREGINRAILKYDPDHE EDAEKLRAGLLNWGGLDE AQADALVAAWRKRPRPDG KRLNMSRRAVRNILALMD RPEPWPDPSSPKHPRWIT QIEARKLIAEDADFLDVT TGEPLDDHARRRYATGAR GATARDRYYMKKHVLRDR EGRPIRDPDGKPLAEPPP APLISNPVVRKAIHEVRR HLVEHMTTFRCKPDEIYI ELAREARMGKKDSDRVLF RNRLRNRIRRDIIHEFGL EDRTSNQQREAVKRVVLT VQQGGVCPLCGNRTVKTR ITERMAADGEGCEIAHIL PRASGGDNRWSNVVLAHK KCNHDMARRTPRQFWSEG QGFDQGMDWVQGIYGEVN RPKPSEVKNASGNSLWAC WFTKRDDHGKIEQFKKDI SDIQQMTARQEAATKYAA RQIQAYLSDALYDGKGLP ERSTGDDKRRIFTSDGLW TSRFRREWGLFFDPHDWK AHDITEKEQHERREKDRG DHRHHAIDAIVIALCDRS IRMRWEDRERHADHDGIN TADEEQMENYRRNNPLPP Petition 870250090553, dated 03 / 10 / 2025, pp. 123 / 262 120 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence PGPFKSREDFREAVRKAV FGDGEERPICHRPVKRKL IGALHKETQQGPVLDTWV KNGIVHREPVEGRVTVRQ NVLGETQTDYLKPAHLRL PRPETDTEARIKARKARKLRQLQLKLKLKL VKSNAFTRAIVDPPKPEKG GIVRDLRLRRLIRRRLEE WGLDPDNYSKADLKRAID EHGPLTMDSGVPIRRVIL LWSNKEPVPIRRDHYDYA TGKRQKMEDPKSLRLYDS QNNHHVEIREDDTDRWSG EVLTAFEVAQRKLAKLRA FREAGIPKRRALPRALPRALPLRPLPLLDLYDYA VDRRDDDQKGGRFVMSLS EGETLHMKHKQTGEVGYF VVAKLDKPRSIVVVPHWD ARKAGPRKDPDGKVVPDS QRDQFAITPTDLKTLAPP GRDHAVKVLVSPLGVVRE LKGD* Effect ores MG8 6 6 Efetor MG849 Protein organism descon not cultivated or with the predicted taxonomy Butyrivi brio sp. CAG:2825 MKILSLDLGVTSCGYSIL KRIEQNSYSLLDYGVVMR DNPNDGGTQQERREKKSS RDLLNKKKARLKDIKQLF KAFNLSYDKKNYDIWKL RAIDAFERKLENDELFSI FRFMAKHRGYKSLKIEDL IAEEKEKLEKLENDELFSI FRFMAKHRGYKSLKIEDL IAEDEKKLENKLENDELDELKYLL LKCKYKEKTAPQIIWEIE SQKENPTFRNHNNYRYMI RREDIEKEISLIIQQQK FNLFENEKKAKEFADAVE NIIIPQEAVTLNPDNINK CLIYKEEKCAPIFSYSFD IFNLYKLISDLKIDGINA SNEQKEELLTSILEDIKN FKSSKLIDKYKKDFKILGINA Petition 870250090553, on 10 / 03 / 2025, page. 124 / 262 121 / 251 Cat. SEQ ID NO: Descrição Tipo Organismo Outras Informações Sequência DNEYVKINNFQEYKTIKG KKELTSLIKFNFVSSFKK LKPEILNAILNKENFVDI LDELSTQLHLNINPQMLI EEAIKVFQEHSLEFEKEV IQEFILELHKHKSKGTSS LVKLKLWEQQNFRGIYSF YSLKTLKDLVVQMKEGKN GKINRNLTIDEILSDKTE IEHIVPRACGGSNAEYNK AIDLKDENAQKGNKLPLD YLTGEKREIYINFVKELK DAKQINFKKFKNLMAEEL KDAYKEAKDDVSLHATSY MEKLLGEILKRYYPFTDL LKENQRVMSISGRATSYL RRILSIDNKSRDTNFHHA EDAILLGLMSKAYLQSIS TNFEKNYEMTEQNAKENF KKIIPLIEGTSPNHIIAH IRESYEEHIEENPFYKAL NGTLKTPAFWVSKKPIGT KAHNETIQSKNNLSYYVP ITSLLDKVKPNHKMNADD FYKLFNKEIYEKIQVVQD NPKDHTAKIFAQRRDEVV NLLNKSAFVSIKEEKAEL DKELREITNQPFFDVNGN EMRRIKRVGEEASIEVRG GLAYTAPSLVCLRCSFID EKKLKLQRIDIRSYAKNK TTNHNQIDIFNNDLTEIF VEKSKTLESKALGLLKGF TESKGGRANLRHPKYPLL KEKQPSLYQKEFSIGSTC Petition 870250090553, dated 03 / 10 / 2025, pp. 125 / 262 122 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence GIKKYKTDATGKILGFYY LGKVPGNNQELFAKVLSY KAL* Effector MG11 2 7 Effector MG112-1 Protein unknown organism or uncultured organism predicted by Buty sponomiri. CAG:2826 MNNQKVILGLDIGIGSIG WGLVQLTEEKYIDEKADG TVIEKYKICDGKIIDSGV RTFQPPQDRQKKKSLAIQR GSARRSRKTIRRKVRRLK RLIKLTKDFGLITEDFNH DSTLKPKKGDIETRWDIW FIRKEALKFERKHFKHGFFKHTFAKH EMQKEESGSEAGEVKKGL TKIRKKIQEGPWETIGQM FCEEFQQTNKGNNKKRNT ENNYQNSIHRLLKDEIE TIFKRQQELGNPKAKEEL KQSYIDEILMKEEPIDED KLQKMMSRCEFIKGKLCA PKESYAAERFELFELVLDNKLLDNKLLDK QKEKIETLAYQNDKVTFV QIRKKLGLQDDLHIRFNL CSYKEKNPEYTKKLECKV EKGRLQFEEKHKIPIVDI NTGEIKILDKEIKKIFQS KKLWPNSKKIYVYSDMR KQLNLSGDFADLRGYT KSTTELNSEDKYIKKYKFEDKVKVKVKVKVKV RCGDKKWCELAADTNNLD IIAESLVYHKSDETRKEY LRESGIVDNEILDAVLTI NMKQLANFSKEAMQKLLD FMEKGVLFNNAKEKAGFG KIEEKQAILKPYSGFFE NNPVVARVISQTRKLINA IIRKYNGKYPIDQISEQIQEQRIQI NRYRQAKEAATERCREEG LDPEEGQNLLMFRLAEQQ NYFCPYTKTKITLYPTGA Petition 870250090553, dated 03 / 10 / 2025, pp. 126 / 262 123 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence ANEVYIKECEIDHVIPMS RSFNDSLNNKVLCTQKAN QDKKDRIPLEWFEEMYGM NSRQWSDFENNIKKMYAM PYSKRRRNLLRKSWTDEDK EKFLSRNNDTRHIARHYARDSLYALDLYF KDVNRIQVRSGGITSFLR HMWGLNKNRGENDLHHAI DALVVACSTYGHVYLVSN LSRQMERKGKNWYKHFGK DKFKPWEQIKEDIQKAAN DIFVSRMPRHTVTAAAHK ETIISKEITDNKRTIRIR GGYAEMGDIKADVNGVVDVDVDVNDVNYVVNYV PLPEKYVPHDRTLPYEQW PSVFDKDLKFMFSIFKDD LISVNDKMYVSFIEAMT VNLNVENIDGSIFTDKED SKEPYIKKIGYRPRSRRRN KCILKKYSVDLLGKYKEI KQEKRLGNRFECQN* Efet ores MG11 2 8 M 1G112 Pro-conh ecido des organism either uncultured or with the predicted taxonomy Butyrivi brio sp. CAG:2827 MNKEKIILGLDIGVGSIG WGLVKINEEEYPDEKPDG TIDKKYRITGGKIIDTGV RTFQIPQDRQKKSLALQR GTARRSRRTTRRKAQRLK QLVKIAREFNLIDENVDR EGIFKPKKGNKKEKWDIW TIRKEALKLKHLTHIKLKLKYKLKYFKYF EIQEEDKKTATGQENAKV KKGLRRIQKMLKDGGYKT VGQMFWEKFKQTDEKNKR KRNAKDKYENAIHRNLLK EEIEIIFDEQRKLGNSKA AKELKERYIDEILMKEEG IDDEKLQKMMSRCEFVSR ALCAPKESFYFNKFLNKTLNKTLNKTLK LDDEQRSEIEALAYKNKK Petition 870250090553, dated 03 / 10 / 2025, pp. 127 / 262 124 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence VTFAQIRKELGLENDLDK RFNLCSYKEKNPEYNKKL ECKVNNGKLNFEEKHKLQ LVNTINGEITVLDKEIKG IFKKRKETWKNANKLYVY YSDIRKQLNISDDFRFAN LKGYTKSESELASKEEYI KQFEEKDIFVELKGYHKI KKAVENCGEGKWVKLKKE TEKLDIISEALVYHKSDE TRTKYLEDKGIVDEDIIN AILAINMKALANHSKEAL KNLLKYMDSEKHMLFNEA KKECGYGKIYYEKQAILQ PYHGFFENNPAVARVISQ TRKLINALLRKYREQYPI DQIHIEVATELANSKKVK DRISRGQRIYKEAKETAA ARCREKGLDPEEGQNLLM FRLAEEQKYFCPYTNTKI TLCPTGATNEVFIKDCEI DHVIPMSRSFNDSLNNKV LCTQKANQDKRDRIPFEW FEETYGKDSKQWAEFENT VKKMYGVPYGKRRNLIRK SWTEKDKESFLSRNLNDT RYATRHIADYLRKYFDFS KRDDIKDVSRIQLRSGGV TAFLRHIWGLNKNREEND LHHAVDALVVACSTYGHV YLVSNLAKEMERKGKNWY KHFGWVRDKFKPWDNIRD DIQSTVNNIFVSRMPRHT VTTGAHKENPESLIEKRR IKKARKRYPKKKIASQPI KNRVIKFNRGYAEIGDMV RADIFVDEAGKHYVVPIY TTDIFTNKPLPDKYVPHD RNIHYEQWPSIFDNDLQF KFSLFKDDLISINDNRYY VSFFEATTVNVNVKNVDG SIFPGKKNSQDPYTKKIG Petition 870250090553, dated 03 / 10 / 2025, pp. 128 / 262 125 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence YRPKDRTKKCALKKFSVD MLGNYKEVKQEKRLGNRL ENKIKKNI* Effector MG11 2 9 Effector MG112-3 Protein unknown cultured organism or cultured organism predicted to be a predicted species. CAG:2828 MGYNKVVLGLDVGVGSIG WGLVQLDEEKYADEKQDG TVEEKYKITDGKIIAAGV RRFQLPQDRQKKSLALIR GTARRSRRTIKRRARRLK RLIELGKEFNLLGNDFDR DKFLIPKKGDKKEKWDTW RFRALFRAKDEKHYFYFYFYFYFYVLG RLELEKDSKAAKDQGEKG EEKQDNEKKKEREKMKKG LKRIQELLKRSQYKTVGA MFYEMFKNGRKRNAPDKY SNSIRRELLHDEINEIFK AQRALGNEKADPDLEKQY LRAVLMQEKGPDDEKMQK MIGRCEIIKELCSQAGKE CTADCLADCLCRCAPKCK YTAERFVLFNRLNSLKII GGQAIDLAKHRDNIEKLA YTHDKIDFSQIRKELCLT DKPHLRFNLCSYSEKNPE YEKTLKYEVSNGQLQFGP EHRVQMDNFDTGETKVFD KEIRAIFQKRLATTPNYK KINGVRYSDIRKELQKGPKGGFKVKFTYKFTKELCLT AQLESEFFTKPKNKGKNF NGDAAYIKQFEDDAIFVE LKGYHKIRKVLENRDGTW EKLKSDGTRIDTIAALT YCKKDETRTAYLKERGIT DESVIDAALTLNMEKIAT YSKEAMVKLLEHMEKGLL VNDAKARCGYDKFEHKQLAPPYFFENVNPVNPV VIAQTRKVVNAIVRKYGE QYPIDQIHIEVATELANS EKTRKRIKDAQDKNKDEK Petition 870250090553, dated 03 / 10 / 2025, pp. 129 / 262 126 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence SRARSICEEFGINSDEGQ NLTMVRLLDEQGHFCPYT GKAIVLRSTGAANEVHIN DCEIDHIIPMSRSFNDGM NNKILCCAKANQDKRNRI PFEWFEETHGPNSQQWFE FTRRVEKYDVPKYSKMNKN LLRKSWTDEEMKKFMDRN LNDTRYATRIADYLRKY FDFSNRRDDIKDVSRIKL RSGGVTAFLRYLCGLNKN RDENDLHHATDALITACA TDGHVFLVSNLSKQIEEK GKNWYKHFGMEKFKPLRP WETVREDILEATQKIFVS RMAHEVKWTSADHEVK FDEKKRTKKAQKKKSSI PKDTARVMKINNGYAKIG EIVRADVFEDGKHKNYVV PIYAVDIFSSKKPLPDKYL KKNNTPYDEWPSAAADNL TFKFSLFKDDLITINGTP YYVDFVEGTQANIKVRNI NGSKFESTNEKRKELKFYKKVKVKVKMLPDKYL KEEKRLGNEGVKWTKKRP KK* Effector MG11 2 10 Effector MG112-5 Protein unknown organism or uncultured or with predicted taxonomy Butyrivi brio sp. CAG:2829 MPEEEEKELNKNRGKKRD PEAQEKEKVKKGLRKIQK LLKNSEYKTIGAFFYETF RNTRKRNAPDKYEHSIRR ELLREEIIEIFKEQQQFG NTKAKEELKQRYIDDILM KEEGIDEKKLLKMMSTCE FVPGERCAPKKTERQTLQLVTLNGTL NRLSLDKDQRDKIIDLAY KNAKVTFTQIRTELKLDN KLHLAFNLCSYKEKDPEY NKKLVFKVKNGQLQFDIK NRLPTIDIDSGNIKILDE EIKKIFKSKKLRPKAKSI Petition 870250090553, dated 03 / 10 / 2025, pp. 130 / 262 127 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence YVYYSDIRKQLNLSENIR FGYFDKKDDTVKELKGYT KSAAELGSEAKYIKQFED DTFVELKGYHKIKKAIEH KCGNEKWEKLSKDVSKFD AIACKSDEALTYKELTYKTEKFD LQNHNITEKEIIDAVLTI NMKQLATYSKEALNNLLK YMDSKECMLFDDAKCG YGKLQYDKQSILKPYSGF FEKNPVVARVISQTRKVI NAILRKYKDKYTIDQIHI EVATELANSEKRKNEISQ GQRRYKEEKEAARKLEERGREGLEGLEGNIQLEQ QQRQLCPYTGKHITFQPT GASNEVCIRDCEIDHIIP MSRSFNDSLNNKVLCSPE ANQNKRDRIPFEWFEETY GKDTQQWEEFENIVKKMY RMPYPKVKNLLRCSWTEK DKEKFLSRNLNDTRYAAR HIADYLRKYFDFSERGVKVCRVCGVRFGG LRYMWGLNKNREENDLHH SLDALVVACSTDGHVYLV SNLAKEIERKGKNWYKHF DFIRNKFKPWPTVREDIQ TKVNNVFISRMPRHKVTA EAHKETVDSRKGKPSNRR VIKLSSRGKLNKCYAEMGH MVRSDVFIDDKLPKVKVYKVYKVYKVYKHV KNNAPYETWPRVEESNLK FKFSLFKDDLISIDGKMY YVNFVRGTRSKINVRSID NSIKEKELGYKNSELKKY SVDMLGNYKEVKQEKRQG NCSERTA* Effect ores 11 Effector MG112-7 Protein desconh acido cultured organism o MIGGGGILG WGLVKLAEKKYIDKKADG TTERFKIKDGEIIDRGI Petition 870250090553, of 03 / 10 / 2025, p. 131 / 262 128 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence MG11 2 o with predicted taxonomy Butyrivi brio sp. CAG:2830 RAFQVPQDDKGKSLALKR GTARRSRKTTRRKVKRLK ELVRLAGEFKLINDDFDR DAILKPNKGDNESNWDIW TIRKEALERKLTGTELFR ILYHIAKHRGFYFHTKAE FLPEEEEKELNRSEKQKR EESQEKKKKKKKKKKKGKGKGQKRLK EEFKQANENNKRKRNAKD KYEHSIHRDLLRKEIEEI FKEQRIFKNDKADVNLEK RYIDEILMCEEGIDDKRL QNMMSKCEFTGEICAPKE SYTAERFTLFNRLNALKP IDTNIKDKPPPLDKNQKE KIIKLAYKNSKVKFTQD NELHIGLQDLQLKSY KEKDPEFDKKLTCDIKNG RPAFKEKKHKLKTANVETG EVEDISKVEEIFNKRAK TYPKKNLYVYSDIRKQ LNLPSDYRFADLKGYTKS AAELGSESKYIDQFEDKG VFVELNGYHKIRRAIENY CRDGQDEKWDELAKDEKSDALKDVYKHELKHEDKH KEKGITDDDIISSVLTIN LKGLANHSNKALRKLLEH MEMGDLFNEAKKKCGYDK IKYDKQTILQPYSGFFEN NPVVARVFSQTRKLINAI VRKHQNQYPIDQIYIEMA TELASSKRRRAQIARGQE RYKQQAKEAKEALEKSEGVLDFQNDFQL NKCPYTGKTITFYPATAD NEVYIRDCEIDHIIPMSR SFNDSLNNKVLCAPEANQ NKRDRIPFEWFEETYGEA SKEWVEYENRVKKMYSMP YSKKRNLLRKSWTEKDKE Petition 870250090553, dated 03 / 10 / 2025, pp. 132 / 262 129 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence RFLSRNLNDTRYAEREIA NYLRKHFDFSKSRRDDIN PLRRIQIRSGITAFLRH MWGLNKDREENDLHHAVD ALVVACSTYGHVYLVSNL SKEIERKGKNFNWHKHK RDKFKPWNNIRGDIQNAV RNVFVSRMPRHKVTGAAH KETVVSKKTANNKRTIEI NKGYAEMGEMVRADVFTD KAGKNYVVPIYSVDIFSN KPLPNRYVPHDRTLAYKD WPRVKNEKLKFKFSLFKD DLISINSKMYSFFEKNYVPNKVPNKVPNKDVFTD NAQNPYTKKICYRPKIKT RKCVLKKYSVDMLGDYKE ILQEKRLGSRFENGL* Effect ores MG11 6 12 Effector MG11643 Protein unknown organism or uncultured or with predicted taxonomy Butyrivi brio sp. CAG:2831 MGYRLGLDLGTNSIGWAL YDLDAKGRPCAIRKLGSR IFPDGRDPQSGASLAADR RLHRQMRRRRDRYIQRRA RFMNALVRHGLMPEDPAA RKALEGLDPYELRARGLT ERLEPCELGRALFHLNQR RGFMSNRESVDKADDIKKERGELGELGELGEL LGAWLWERHREREGVRAR TTGAGPKSGYVLYVHRDM IADEFDTLWARQRAHHPK LLTEEARVRLRGILLWQR PLKPVRPGRCTLDADDER APWALPVAQRFRVLQELN HLAVQGPGVAARPLTPAE RNRLRDALLGQAKVTFER MRGDLWLDLRQLDLRTAGLLGLL RFGKGWDKLPPEEQAEVV ERLLSHEADEDTLAEWLR KRFGLADANARKVATARL PDGHARFGRKALAKIVPL LDAQVVTLDKVVEAAGYD。 Petition 870250090553, dated 03 / 10 / 2025, pp. 133 / 262 130 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence PHFRPPAEPQPALPYYGI PLAAHVMPADTAGDPVER EHGRIGNPTVHVALNQVR KVVNEIIRRHGNPDQIVV ELARDLKSSREQRREYEQ VNAENRRRNEGYAGRLAD SGLPDNAENRMRMRLWEE LGPDPLDRPCVYTGEQIG FARLFKPEVEIDHVLPFS RTLDDGIGNKTVSLRRAN RDKAQRSPHEAFAHSPAG YDWDAIVARAATLPPNKR WRFAADAMERFEAQEGDL KGFLARHLNDTRYLSRLA KAYLGWVCPPNRVWVTPG RLTEMLRGKWGVNKLLGE GDAKNRNDHRHHSIDAAV VGVTDRSLLMNVAHAAGL AEMRGAGRVLETVPLPWP EFHRDLEAAVGRIVVSHK PDHGLGGQLHEETAYGKV GGPDAKGYLTLQVHKPLS GLGPGNLKDMVDDNLRER LTAATAGLAGPDFKRAVA DLARETGIRRVRVEVTKQ NKAVVPVGSPPYKYYPGG SNYCVEIVEEAKGDKRLW KGQFITTFEARNKAYRAF RQDTARYRTASFLGQPLV MRLIAGDAVALERPEDQG RRTIWRVRKLSQNGQINL DPHREGGDFAKRDKDPDD PFKSWAPRINTLRELKAR RVFVDILGRVKDPGWGDA RTDRGDRPGGVSPARGAR VPGGAGGP* Effectors MG11 6 13 Effector MG11644 Unknown protein uncultured organism with taxonomies MGYRLGLDLGTNSIGWCL LDLNDKGQPEATLGGGAR IFSDGRHPKDGTSLAAKR RHARQMRRRRDRYVARRE RFIEALVRHRLMPPDQQA RKALEQLDPYSLRARGLK Petition 870250090553, dated 03 / 10 / 2025, pp. 134 / 262 131 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Predicted Sequence Butyrivi brio sp. CAG:2832 GRLEPCELGRALFHLNQR RGFKSNRIADEADEKERG RIRSAIEDTRARLAAAGF ETVGAYLADRNRRREGTR ARLTGTGRKDPYALYVHR DMIAHEFDTLWERQRRHN PEVLTDAARDELRDILLY QRDLLPVDPGPCTLDPRE RRAPVALPGSQRRRILEE LNHLRVIDADHRSRPLTL DERNTLAQLLRTREKLTF AGMRKELRLPREVAFQAG TERRDFFKGDETAARLRK EDRFGEAWDRLSLDEQTE VVEKLLSEVDEGAVEAWL RERWGLPAGRSAAVARMR LPQGYGRFGRTATAKVVA ALEANVIPASEAVERAGY DAHIRSNGTAEELPYYGE VLTRYVAPAPRAKNAAER EHGRIANPTVHIALNQLR KVVNAVMARYGRPDEIVV ELARELKQSQRQKDEYEK RRKENEARNERHNRLLIE HHQEANGENRLRLRLWEE LNADDPMDRRCVYTGKQI NIATLFSGTVEVDHLLPF SLSLDDGIGNKVLCLRQA NRDKGRQTPYQAFGHSPG EYEWGDISARAEALPENK RWRFAPDAMEQFEARANF LERHLNDTRYLSKVARAY LSVVCPPERVWVTPGRLT QMLRGKWGLNKILGKEEA KNRNDHRHHLIDAAVVGV TDHWLLNRMARAASQAED RGAGRVLEHLPAPWPNFK DDLEILAGRCMVSHKPDH GAEGALHNDTAYGMVSGP DHRGAYTVRHRVMLSSLK GPKDLDKVAPPRLRAQIK DALSGYNETDFRRTIARF Petition 870250090553, dated 03 / 10 / 2025, pp. 135 / 262 132 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence SEETGIRRRVRVEEVLSVF PVRNKEGYSYKWLKGDSN YCAEIVRESNGAWKIELI PTFRANQPDFQEFLRDRA HCFQRSFSGKPLIMRLCK DDTLAIGTEQSRRILLVT ELNEKRLVLIRPNEGGNL KMRHADTDDPFRKEFMGP STLKKLKARRVFVDILGR VKDPGWGDARTDRGDRPG GVPPARGARVPGGARGG* Effector MG11 6 14 Effector MG11645 Protein unknown organism not cultured with predicted taxonomy Butyrivibrio sp.CAG:2833 MQIPYRLGLDIGTNSIGW SVLPLDGDGRLERLGDII ALGARVFPDGRDPASGTS LAVERRDPRQHRRRRDRY LRRRRRFMAALIQHGLMP DSEPERCTLESLDPYELR GRGVVAPLSLHELGRALF HLNQRRGFKSRDKKDKDRKDRQREQREGREQRGRE MDAVGAETYGAYLSRRRA QCKPVRVRLAGVGKGERY DFYPDRELAEQEFDALWA FQQPHHPEHLTEAARATL RDILLYQRPLKPVKPGRC AFEPEDERAPMALPSAQR FRLLEELNHLRVALPGTS ARPLTLEERNRLLAALQR KKTMSFADKARGADELGELGELLL AALSKPALFGAAWHALD LQRQDEVVEKLLIENDES VLVAYLRDAAGLSIQQAE AVSDLELPDGYLRLGRTV LGKLVPALEAAVVTYADA VKQAGYHHSQLLTGELRD ELPYYGELLERHVGFATG DPNHIPEVRYGRIANPTV HIGLQNQLVKLVLKLGLGRTV GRPAQIVVELARDLKQSK KEKERLERLQATHQAQNE QHRARLQELGLPVNGENL. Petition 870250090553, of 03 / 10 / 2025, p. 136 / 262 133 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence KRLRLWEELNPANDLDRH CVFTGQQISISMLFSDAV ETEHLLPRSRTLDDSFAN KTLCLRRANRAKASQTPY EAFSHSPPGYDWDAILER SAGLPANKRWRFAPDAMQ QFAEDGDFLARHLNETLH LSRAAKEYLSAICPPNQV YVTPGRLTALLRREWGFA KSRDDHRHHALDAAIVAC TDRATLQAASRAAARCEE QGLNRFIDSLDPPIEHFR EKLLTKLERTVVSHKPDH GTEGALMNGTAYGFVSDP GGTGPATVVHRMKVADLK DEKGIAKIRDACIREALL RHVQEHPGTWKEKLNNYS EKTSIRRVRVVERYTVIP IRAEAHGEPYKAYRGDGN YCYEIVRNAGGGWSGEVI STFLANSASYRDFRRDLK RFRSFAFSGDSLVMRLCK NDFVAIEPDDGRRRIMLV VGVSEGNITLGEHFEAGD LRSRHKEAGDAFRYIFKA PSKLPVLRARRVFVDFLG RVKDPGFHP* PI Domain of MG2 Effectors 15 PI Domain of MG2-4 Protein unknown uncultivated organism with predicted taxonomies Butyrivi brio sp.CAG:2834 ALITKDGSPRLDVIPYIN VHQWLEVLALENGGGSPV VLRKGHLVGFDAEKCPEE YCGAWMLLGVKDGRSGTT LELIRPWMVAPRKGGTKE SSAKQAIKPASGYSEKEG KASGVFLQRSADVFLKLG LRPLDHDLTGIAAF Domain PI of 16 Domain PI of MG2-90 Protein derived from the organism or not cultivated with AILCDEKLPPEERLVIIP HAKVWHRLQDLKQLNGGK LPSIWRNGQIIELTKGKR AGRWRIFSIKNNTSGMAL. Petition 870250090553, 03 / 10 / 2025, pág. 137 / 262 134 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence Effectors MG2 predicted taxonomy Butyrivibrio sp. CAG:2835 DLGSVEAVKATWINCLLK SLLRDGAQRLSTTLIGAR QLSA MG4 Effector PI Domain 17 MG4-1 PI Domain Protein unknown organism not cultured with predicted taxonomy Butyrivibrio sp. CAG:2836 EIVESTDPENEKINWEGL VVSLFEAYQRKKNGTPIV RREFGVNKKFLFSLANGD IIELDNAEGTARGLFIVR TVRKSKQIKFVPINDARA YKQDMWGGLTAKPDSLRR RRCRKLTVTPLGDVRTAN D PI Domain of MG4 Effectors 18 PI Domain of MG4-2 Protein unknown organism o not cultivated with predicted taxonomi Butyrivi brio sp. CAG:2837 EIIEVRDAKGGKKWTGRL VHRLEAKRRALGRETIVD RAVQAGRQFQFSLSPGDM IELTGEDGERKLHVVRSI SEGRIEYVDARDARKKAD IRASGDWRKPAVGSLLRL HCRKVVVTPFGEIRYAND PI domain of MG4 Effectors 19 PI domain of MG4-3 Unknown protein uncultured organism o with predicted taxonomi Butyrivi brio sp.CAG:2838 VIVAELADKTDPNTGERL EDRWVDKVVSRLGAYRRL AACKRAGRPDQVVRRDWG GKRRFKFSLTGGEFVEME DDGGERCLYRVYTISKGD MWFRLHSDARLKKDITAA GDHVRCSGEKLRRRKARK VRVTHLGDIVPAHD. Petition 870250090553, dated 03 / 10 / 2025, pp. 138 / 262 135 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence Effector PI Domain MG4 20 Effector PI Domain MG4-4 Protein unknown organism not cultivated with predicted taxonomy Butyrivibrio sp. CAG:2839 EVYAVLDENGVEKEWRSK VVSTFDAYERKRRKKPVV QRDFGPDARFLFSLALNE IVALQDGELLVVSGISQG VELECKRINDARSATRRK AEKTRVRFTSATGNFMPV GFRKMRIDVLGNVFPANE Effector PI Domain MG4 21 Effector PI Domain MG4-220 Protein unknown organism not cultivated with predicted taxonomy Butyrivibrio sp. CAG:2840 AIVASLDERGNEVRWEGH VVSLLEATQRYSRGEPVV QRDWGVNRYFKFSLTAGE FLSQEHEGKEQLVRVVSV SENDIESVLHTDARPITE RKKIKGARIRGGPDKLRQ RQACKVSITPLGDVVPAN D Effector PI Domain MG4 22 PI Domain MG4225, MG4227, MG4230, MG4233, MG4236, MG4-221 Protein unknown uncultivated organism with predicted taxonomies Butyrivi brio sp.CAG:2841 EIVESTDPENEKINWEGL VVSLFEAYQRKKNGTPIV RREFGVNKKFLFSLANGD IIELDNAEGTARGLFIVR TVPKSKQIKFVPINDARA YKQDMWGGLTAKPDSLRR RRCRKLTVTPLGDVRTAN D Domí nio PI de Efet ores MPI 125 MGnio de Mi-5-5 Protein unknown organism or uncultured or com taxonomy predicted AIRENRKTGRWSGKVVRM FEAARRVRPAQSPDGSRE GPRPAVDRSDHANARFVM SLAEGEMIYARRKDRPEE LADYFVVCKIDPSGRIHL APHWDARKAPPSDKKKRT SEHQDRWDAVPAHLEDCGG. Petition 870250090553, of 03 / 10 / 2025, p. 139 / 262 136 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence Butyrivi brio sp. CAG:2842 PEPGNPPYKVHVGPLGEV HRLDRD Effector PI Domain MG5 24 Effector PI Domain MG5-2 Protein unknown organism not cultivated with predicted taxonomy Butyrivi brio sp. CAG:2843 ALFEWHVNGKRKRGAAFV TMLEAMKRVKKHERIIQR TPPINHQTIPPDATFLFS LSGGEMVLAQVNGQEQLL VYDTAAQTSEQMWFYLHT DARKQADKKRYSYKPNTL RARKVTVDPLGRIRWAND Effector PI Domain MG5 25 Effector PI Domain MG5-3 Protein unknown organism not cultivated with predicted taxonomy Butyrivi brio sp. CAG:2844 EIREDKKGNWKGDPVTLF DAARRVRPPKDTGLASTT AVDRTDNKDGKFIMSLCI GDTVHMAHPLKEGVVDYF VVFKFSGNRIYFTPHYST GKAQPKDESKRKRSEIYR EEIEVPVSKLKKLMVFNN SIPEKVAISPLGDIRVLV KN MG5 Effector PI Domain 26 PI domain of MG5-4 Protein unknown uncultivated organism with predicted taxonomies Butyrivi brio sp.CAG:2845 IYWAQGEGEDEKWSADVI TMWDAARRARAGLPSVDT TPPRGKRFVMSLSLGEMF EMVGDDGEIKLCVVRKMD QRSKRVYYKVHTDARETD LVNKDNLYLSPKKMQERS ARKVTVDPLGRIRWAND PI Domain of Effect 27 PI Domain of MG5-5 Protein unknown organism not cultivated with taxonomi EIREDDTDRWSGEVLTAF EVAQRKLAKLRAFREAGI PKPDAFRALPRAERRKLR PILRDIELGHPLVDRRDD DQKGGRFVMSLSEGETLH. Petition 870250090553, dated 03 / 10 / 2025, pp. 140 / 262 137 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence MG5 predicted Butyrivi brio sp. CAG:2846 MKHKQTGEVGYFVVAKLD KPRSIVVVPHWDARKAGP RKDPDGKVVPDSQRDQFA ITPTDLKTLAPPGRDHAV KVLVSPLGVVRELKGD MG6 Effector PI Domain 28 MG6-1 PI Domain Protein unknown organism not cultured with predicted taxonomy Butyrivi brio sp. CAG:2847 EIFEYTDKKGKVKRGGNV VTMFEAIHRSQRGESVIQ RDHGQDKKFICSLAQNEM FMLKIDNDEEVLHRIQKI DQNKRIILRPHTYGGKLS DLDKPPLIQRKSANTIEG YKVTVDPLGRIWPAND MG6 Effector PI Domain 29 MG6-2 PI Domain Unknown protein not cultivated organism with predicted taxonomy Butyrivibrio sp. CAG:2848 EIFEYTDKNGKTKRGSKV VTMFEAVQRSQRGEPVVQ REHGQCRKFICSLAQNEM FMLESEKGLTDLYRIQKI NQNGQVFLRPHTYSGDLT KQKAVSKLPNKLKGHKVT VDMLGRVHMAND PI domain of MG6 Effectors 30 PI domain of MG6-3 Unknown protein organism not cultivated with predicted taxonomi Butyrivi brio sp.CAG:2849 AIYETSDKNGVKKQIGIV IPMMEAARRVKDGDPIVM KDYRPDHTFLYSLAKNDM IFNHEDEQIYRVQKINSD GTIMFRQNNVAMKGQSDP GVYFKSGSRLGASKIKIS PIGEIFPAND. Petition 870250090553, dated 03 / 10 / 2025, pp. 141 / 262 138 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence Effector PI Domain MG6 31 Effector PI Domain MG6-4 Protein unknown organism not cultivated with predicted taxonomy Butyrivibrio sp. CAG:2850 EVITNDDGQYDGRVVSMM ESSRRARAGESMRRRGSK GMSSIVQRDHGDGRFVMS LHKNDTVLMDTPEGKDQL FRVQKFGITSGSPDIVFC HYSASRPKSPSKLKPWEK FKGTRAWSKFTKFNVRKV AVDVLGDISFPGD Effector PI Domain MG6 32 Effector PI Domain MG6-5 Protein unknown organism not cultivated with predicted taxonomy Butyrivibrio sp. CAG:2851 EIFEYKDKKGGKKRDGRV ITMFDAVQRSQKRESVVK RDYGDGKEFVCSLATNEM FIMDNVDGNTELYRIQKI TQSGNNKTIILRPHTYAG KLSDSDKPPLIQRKSPNT LKGHKVTVDMLGRFHMAN D PI Domain of MG6 Effectors 33 PI Domain of MG6-6 Unknown Protein Organism o not cultivated with predicted taxonomi Butyrivi brio sp.CAG:2852 EIFEYTDKKGKMMRGGEI VTMFEAVKRKREDQPVIK RECGADKKFICSLAMNEM FMLDTNNEEKELHRVQKI TQSGNSISIILRPHSYAG KVSDYDKPPIIQRRSPNT LKGHKVTVDMLGRVHLAN D Domí nio ores EPINIO 34 Domínio de Minio de Minio MG6-14 Protein desconh acid organism o not cultured o com taxonomy a predicted Functions EIFEYEDKKGQTKRDGRV VTLYEAVRRSRKGEAVIC RDYGDGKRFICSLSQNEL FMLKIGEDDELILHRIQK LSSNSQIYFRRHTFAGDLQENLLPKKGKVKHGVKVKV. Petition 870250090553, of 03 / 10 / 2025, p. 142 / 262 139 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence brio sp. CAG:2853 MG6 Effect PI Domain 35 MG6-16 PI Domain Protein unknown organism or uncultivated organism with predicted taxonomy Butyrivi brio sp. CAG:2854 EIFEYTDQKGKKKRVGRV ITMFEAVQRRLNEEPIIQ KDYEDDKKFICSLAQNEM FMLEIEDGEQKLYRVQKI TQSGNNITIVLRPHTYSG KVSDYDKPPIIQRRSPNT LKGHKVTVDMLGRVLLAN D Domí niores EPIores Domíno 36 MPIORES of MG6-19 Protein unknown organism or uncultivated or with predicted taxonomy Butyrivi brio sp. CAG:2855 EIFENIDRKGKKRRTGRV ITMFESVQRSQRGESVVC RDYNDGKKFVCSLTQNEL FMLELDDNRTILHRIQKI TQSGTNISIILRPHTYAG RVSDSDKQPIIQRKSPNT LKGQKVTVDMLGRIHLAN D Domí niores EPINIO DEMINIO DEMINIO 37 M MG7-1 Protein unknown organism or uncultured or with predicted taxonomy Butyrivi brio sp.CAG:2856 TVYQKEDGKYDKVTSFW EAFELKKAKMPIYKENDD AAKAVLHLKINDMVLVDL NPEDLDQNDPEFFNTLSE HLYRVQKLASGDVTFRHH LETELSNKNTEVRVTNAE SLYNRVVMYPLDVLGLPK Domain Domain EPI38 MG16-1 Protein desconh acid organism o not cultivated o com taxonomy a AIYKDQSGQYQEMVVSFW DAVERKLYGVPTVITNPK TVWDELLEKELPQDFLEK LPKDNWQYVLSSMQENEMF VLGMEEDEFNDAIDTQDY NTLNKHLKHLKHAVQDY. Petition 870250090553, of 03 / 10 / 2025, p. 143 / 262 140 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Predicted MG16 sequence Butyrivi brio sp. CAG:2857 TFRFHTETKVDDKYDGVE NGRNTSMSLKALVRIRSF NGLFTQFPHKVKIDIMGR ITKA MG49-39 Effector PI Domain MG49-20 PI Domain Protein unknown organism not cultured with predicted taxonomy Butyrivi brio sp. CAG:2858 DLYKVENDGYYFVPVYVS DLVKDKLPNKASVASKPY EDWKEMKEEDFLFSVYPN DLLLIEHKKDMKFGCTFK DSKLPKEYLSKKEFVYYK KAGISTASITVITHDNSY EIPSVGIKTLANIEKYHV DVLGNKYKAPKEVRK PI domains of MG8 effectors 6 40 PI domain of MG86-49 Protein unknown uncultivated organism with predicted taxonomies Butyrivi brio sp. CAG:2859 RCSFIDEKKLKLQRIDIR SYAKNKTTNHNQIDIFNN DLTEIFVEKSKTLESKAL GLLKGFTESKGGRANLRH PKYPLLKEKQPSLYQKEF SIGSTCGIKKYKTDATGK ILGFYYLGKVPGNNQELF AKVLSYKAL PI Domain of MG11 Effectors MG112-1 Unknown protein uncultivated organism with predicted taxonomies Butyrivi brio sp.CAG:2860 DVFVDKNGGNYVVPIYSV DIFSNKPLPEKYVPHDRT LPYEQWPSVFDKDLKFMF SIFKDDLISVNDKMYYVS FIEAMTVNLNVENIDGSI FTDKEDSKEPYIKKIGYR PRSRRNKCILKKYSVDLL GKYKEIKQEKRLGNRFEC QN PI Domain 42 PI Domain MG112-2 Unknown protein uncultured organism DIFVDEAGKHYVVPIYTT DIFTNKPLPDKYVPHDRN IHYEQWPSIFDNDLQFKF. Petition 870250090553, dated 03 / 10 / 2025, pp. 144 / 262 141 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence of Effects MG11 2 o with predicted taxonomy Butyrivi brio sp. CAG:2861 SLFKDDLISINDNRYYVS FFEATTVNVNVKNVDGSI FPGKKNSQDPYTKKIGYR PKDRTKKCALKKFSVDML GNYKEVKQEKRLGNRLEN KIKKNI Domi nio PI de Efet ores MG11 2 43 PI-13 M Domínio de Proteína 23 unknown organism or uncultivated or with predicted taxonomy Butyrivi brio sp. CAG:2862 DVFEDGKHKNYVVPIYAV DIFSKKPLPDKYLKKNNT PYDEWPSAAADNLTFKFS LFKDDLITINGTPYYVDF VEGTQANIKVRNINGSKF ESTNEKTRKFGYRNIELK KFSVDMLGNYKEVKEEKR LGNEGRPVK omit DofetK EWTPIK MG11 2 44 PI domain of MG112-5 Protein unknown organism or uncultured or with predicted taxonomy Butyrivi brio sp. CAG:2863 DVFIDDKGKNYVVPIYTV DIFSKNPLPNKYLHKNNA PYETWPRVEESNLKFKFS LFKDDLISIDGKMYVNF VRGTRSKINVRSIDNSIK EKELGYKNSELKKYSVDM LGNYKEVKQEKRQGNCSE RTA MEDICAL DOCUMENTS E12 ofet 45 PI domain of MG112-7 Unknown protein uncultured organism with predicted taxonomy Butyrivi brio sp.CAG:2864 DVFTDKAGKNYVVPIYSV DIFSNKPLPNRYVPHDRT LAYKDWPRVKNEKLKFKF SLFKDDLISINSKMYVS FFEATTVNVNVKNIDGSI FPNKKNAQNPYTKKKICYR PKIKTRKCVLKKYSVDMLKFILKGLKF. Petition 870250090553, of 03 / 10 / 2025, p. 145 / 262 142 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence Effector PI Domain MG11 6 46 Effector PI Domain MG11643 Protein unknown organism not cultivated with predicted taxonomy Butyrivibrio sp. CAG:2865 EIVEEAKGDKRLWKGQFI TTFEANRKAYRAFRQDTA RYRTASFLGQPLVMRLIA GDAVALERPEDQGRRTIW RVRKLSQNGQINLDPHRE GGDFAKRDKDPDDPFKSW APRINTLRELKARRVFVD ILGRVKDPGWGDARTDRG DRPGGVSPARGARVPGGA GGP Effector PI Domain MG11 6 47 Effector PI Domain MG11644 Protein unknown organism not cultivated with predicted taxonomy Butyrivibrio sp. CAG:2866 EIVRESNGAWKIELIPTF RANQPDFQEFLRDRAHCF QRSFSGKPLIMRLCKDDT LAIGTEQSRRILLVTELN EKRLVLIRPNEGGNLKMR HADTDDPFRKEFMGPSTL KKLKARRVFVDILGRVKD PGWGDARTDRGDRPGGVP PARGARVPGGARGG MG11 Effector PI Domain 6 48 PI domain of MG11645 Unknown protein uncultivated organism with predicted taxonomies Butyrivi brio sp.CAG:2867 EIVRNAGGGWSGEVISTF LANSASYRDFRRDLKRFR SFAFSGDSLVMRLCKNDF ​​VAIEPDDGRRRIMLVVGV SEGNITLGEHFEAGDLRS RHKEAGDAFRYIFKAPSK LPVLRARRVFVDFLGRVK DPGFHP PAM guide ures o de guide o 349 active PAM o unique MG112-3 nucleotide ideo artificial sequence nnRTCY. Petition 870250090553, of 03 / 10 / 2025, p. 146 / 262 143 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence MG11 2 sgRN Sequence Active effectors MG11 2 50 MG112-3 sgRNA nucleotide artificial sequence N(24)GUUAUAACUUCGG UUAUAAUAAAUCUUCGAA AGAAGAUGCGGAGUCUGC CAUUUUCGGUAUCUCCUC AAUAUUAUAACUAUUCAG GGGCGAGAUCACUUCUCG CCCCUUCCUUUU Trac rRNA sequence active effectors MG7 51 tracrRN A MG7-1 nucleotide artificial sequence ACGAUUUGAAGUUAUUCA CAAUAAGGAUUAUUCCGU UGUGAAAACAUUUAAAGC GGCCCUCGGGUCGCUUUU U Trac rRNA sequence effect MG112-3 nucleotide artificial sequence UUGAGAGCAAGUUAUAAU AAAUCUUCGAAAGAAGAU GCGGAGUCUGCCAUUUUC GGUAUCUCCUCAAUAUUA UAACUAUUCAGGGGCGAG AUCACUUCUCGCCCCUUC CUUUU Target sites MG2 VEGF A_T2 2 53 Site 1 MG2-4 VEGFA_T 22 nucleotide artificial sequence CAAACTCCCCCCACCCCC TTTC Petition 870250090553, dated 03 / 10 / 2025, pp. 147 / 262 144 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence Target Sites MG2 VEGF A_T2 2 54 Site 2 MG2-4 VEGFA_T 22 nucleotide artificial sequence GCCAGAGCCGGGGTGTGC AGAC Target Sites MG2 VEGF A T2 55 Site 3 MG2-4 VEGFA_T 2 nucleotide artificial sequence GGACGCGGCGGCGAGCCG CGGG Target Sites MG2 VEGF A T2 56 Site 4 MG2-4 VEGFA_T 2 nucleotide artificial sequence GCCCGCGCCCGGAGGCGG GGTG Target Sites MG2 VEGF A T2 57 Site 5 MG2-4 VEGFA_T 2 nucleotide artificial sequence Target sites CAGGGGCCGGAGCCCGCG CCCG Target sites MG2 VEGF A T2 58 Site 6 MG2-4 VEGFA_T 2 nucleotide artificial sequence CTTCTGGGCTGTTCTCGC TTCG Target sites MG2 HBBR01 59 Site 9 MG2-4 HBB-R01 nucleotide artificial sequence TGCCGTTACTGCCCTGTG GGGC Target sites MG2 60 Site 10 MG24 HBBR01 nucleotide artificial sequence GAGGCCCTGGGCAGGTTG GTATC Petition 870250090553, dated 03 / 10 / 2025, pp. 148 / 262 145 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence HBBR01 Target Sites MG2 HBBR01 61 Site 11 MG24 HBBR01 nucleotide artificial sequence AGATGCACCATGGTGTCT GTTT Target Sites MG2 HBBR01 62 Site 12 MG24 HBBR01 nucleotide artificial sequence GCAGTAACGGCAGACTTC TCCT Target Sites MG2 HBBR01 63 Site 13 MG24 HBBR01 nucleotide artificial sequence CATCCACGTTCACCTTGC CCCA Target Sites MG2 HBBR01 64 Site 14 MG2-4 HBBR01 nucleotide artificial sequence GTAACCTTGATACCAACC TGCC Target sites MG2 HBBR01 65 Site 15 MG2-4 HBBR01 nucleotide artificial sequence GAAGTTGGTGGTGAGGCC CTGGG Target sites MG2 HBBR01 66 Site 16 MG2-4 HBBR01 nucleotide artificial sequence GGTTGGTATCAAGGTTAC AAGA Target sites 67 Site 1 MG4-2 HBB-R01 nucleotide sequence CCAACTTCATCCACGTTC ACCT Petition 870250090553, dated 03 / 10 / 2025, pp. 149 / 262 146 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence MG4 HBBR01 artificial Target sites MG4 HBBR01 68 Site 2 MG4-2 HBB-R01 nucleotide artificial sequence AACGTGGATGAAGTTGGT GGTG Target sites MG4 FANC F 69 Site 3 MG4-2 FANCF nucleotide artificial sequence GCACTACCTACGTCAGCA CCTG Target sites MG4 FANC F 70 Site 4 MG4-2 FANCF nucleotide artificial sequence AAGGCCCGGCGCACGGTG GCGG Target sites MG4 FANC F 71 Site 5 MG4-2 FANCF nucleotide artificial sequence AGGGATTCCATGAGGTGC GCGA Target sites MG4 VEGF A_T2 72 Site 6 MG4-2 VEGFA_T 2, Site 2 MG16-1 VEGFA_T 2 nucleotide artificial sequence CCCCGCCTCCGGGCGCGG GCTC Target sites MG4 VEGF A T2 73 Site 7 MG4-2 VEGFA_T 2 nucleotide artificial sequence AAAGTTTCAGTGCGACGC CGCG Petition 870250090553, dated 03 / 10 / 2025, pp. 150 / 262 147 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence Target Sites MG4 VEGF A_T2 2 74 Site 8 MG4-2 VEGFA_T 22 nucleotide artificial sequence GGGGTGGGGGGAGTTTGC TCCT Target Sites MG4 VEGF A_T2 2 75 Site 9 MG4-2 VEGFA_T 22 nucleotide artificial sequence CAGCTTCCCTGTGGTGGC CGAG Target Sites MG4 EMX1 76 Site 10 MG4-2 EMX1 nucleotide artificial sequence CCTTCTTCTTCTGCTCGG ACTC Target Sites MG6 Albumin_T10 1 77 Site 1 MG6-3 Albumin_T101 nucleotide sequence Artificial sequence TTTGCGCACTAAGGAAAG TGCA Target sites MG6 HBBR01 78 Site 2 MG6-3 HBB-R01 nucleotide artificial sequence ACGTTCACCTTGCCCCAC AGGG Target sites MG6 Apolipoprotein 79 Site 3 MG6-3 Apolipoprotein_T524 nucleotide artificial sequence TATTTGAGCAAGGCAAAC ATCC Petition 870250090553, dated 03 / 10 / 2025, pp. 151 / 262 148 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence T524 Target sites MG6 Apolipoprotein T4 80 Site 4 MG6-3 Apolipoprotein T4 nucleotide artificial sequence TACAGTAAGCAAAACAAG GTCC Target sites MG6 Fibrinogen T16 81 Site 5 MG6-3 Fibrinogen T16 nucleotide artificial sequence AGTAAGGCAATACGCTTT TCCG Target sites MG6 Fibrinogen T16 82 Site 6 MG6-3 Fibrinogen T16 nucleotide artificial sequence TGCAGTATCAGAAGAGAT TAGT Target sites MG6 HEKs site 2 83 Site 7 MG6-3 HEKsíti o2 nucleotide sequência artificial ial CTGAGCTAACTGTGACAG CATG Target sites MG6 sgRNA A2 84 Site 8 MG6-3 sgRNA2 nucleotide sequência artificial ial TTATTATTATTACATGTC TGAG Petition 870250090553, dated 03 / 10 / 2025, pp. 152 / 262 149 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence Target Sites MG6 sgRNA A2 85 Site 9 MG6-3 sgRNA2 nucleotide artificial sequence TAATAATAATAAATAACA CATC Target Sites MG6 GUCY 2D 86 Site 10 MG63 GUCY2D nucleotide artificial sequence TTCGGATGCTGGAGCAGT ACTC Target Sites MG7 Albumin_T10 1 87 Site 1 MG7-1 Albumin_T101, Site 1 MG15-1 Albumin T101 nucleotide artificial sequence TGCAAAGTAACTTAGAGT GACT Target Sites MG7 Albumin_T10 1 88 Site 2 MG7-1 Albumin a_T101, Site 5 MG7-1 Albumin a_T101, Site 2 MG15-1 Albumin a_T101, Site 5 MG15-1 Albumin a T101 nucleotide artificial sequence CGCAAAAGAAAATTACAG TCAC Target sites MG7 Albumin 89 Site 3 MG7-1 Albumin a_T101, Site 3 nucleotide artificial sequence AATTACAGTCACTAAACA ATTC Petition 870250090553, dated 03 / 10 / 2025, pp. 153 / 262 150 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence _T10 1 MG15-1 Albumin T101 Target sites MG7 Albumin _T10 1 90 Site 4 MG7-1 Albumin_T101, Site 4 MG15-1 Albumin T101 nucleotide artificial sequence TTTATTAATAAGATAACC TTGT Target sites MG7 VEGF A_T2 2 91 Site 6 MG7-1 VEGFA_T 22, Site 6 MG15-1 VEGFA_T 22 nucleotide artificial sequence TCAGAAATAGGGGGTCCA GGAG Target sites MG7 VEGF A_T2 2 92 Site 7 MG7-1 VEGFA_T 22, Site 7 MG15-1 VEGFA_T 22 nucleotide artificial sequence CTTTAGCCAGAGCCGGGG TGTG Target sites MG7 VEGF A_T2 2 93 Site 8 MG7-1 VEGFA_T 22, Site 8 MG15-1 VEGFA_T 22, Site 3 MG21-1 VEGFA_T 22 nucleotide artificial sequence ACGGCAGTCACTAGGGGG CGCT Sites 94 Site 9 MG7-1 nucleotide sequence AAACTCCCCCCACCCCCT TTCC Petition 870250090553, dated 03 / 10 / 2025, pp. 154 / 262 151 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Target sequence MG7 VEGF A_T2 2 VEGFA_T 22, Site 9 MG15-1 VEGFA_T 22 artificial Target sites MG7 VEGF A_T2 2 95 Site 10 MG71 VEGFA_T 22, Site 10 MG15-1 VEGFA_T 22 nucleotide artificial sequence TTTCCAAAGCCCATTCCC TCTT Target sites MG16 VEGF A T2 96 Site 1 MG16-1 VEGFA_T 2 nucleotide artificial sequence ACGCGGCGGCGAGCCGCG GGCA Target sites MG16 VEGF A T2 97 Site 3 MG16-1 VEGFA_T 2 nucleotide artificial sequence TGTTCTCGCTTCGGAGGA GCCG Target sites MG16 EMX1 98 Site 5 MG16-1 EMX1 nucleotide artificial sequence AACGGCAGAAGCTGGAGG AGGA Target sites MG16 Transferrin 99 Site 6 MG16-1 Transferrin_T 100 “ nucleotide artificial sequence TACTGAGGCTTATGTTCC ATGG Petition 870250090553, dated 03 / 10 / 2025, pp. 155 / 262 152 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence _T10 0 Target sites MG16 Transferrin _T10 0 100 Site 7 MG16-1 Transferrin_T 100 “ nucleotide artificial sequence TTGTCTCCTCCCATCACT GTCC Target sites MG16 Apolipoprotein_T4 101 Site 8 MG16-1 Apolipoprotein_T4 nucleotide artificial sequence CTTTTCTAAGACAAATTT TACT Target sites MG16 Apolipoprotein_T4 102 Site 9 MG16-1 Apolipoprotein_T4 nucleotide artificial sequence TACGCATTTGGGTAGTTT TCTG Target sites MG16 Apolipoprotein_T4 “ 103 Site 10 MG16-1 Apolipoprotein_T4 nucleotide artificial sequence GTCATAGATGACCAAGCT TGGC Target sites 104 Site 4 MG16-1 nucleotide sequence AAAGCCCATTCCCTCTTT AGCC Petition 870250090553, dated 03 / 10 / 2025, pp. 156 / 262 153 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence MG16 VEGF A_T2 2 VEGFA_T 22 artific ial Effectors MG17 1 105 Effector MG171-1 unknown protein Uncultured organism MERPSVYGGIGWGW AVVALNENAEPYGLIRCG SRIFDAAEQPNTGESLAA PRREARSTRRRLRRRSLR KADLYELMAQNGLPGRAK IEEAVQAGHLPDIYALRV QALDGPVTAMDFARILLH LMQRRGFRSNRKADDAQK DGKLLQAIDANTRRMEEN HYRTVGEMMRDSERNKHVLQLQL EEAVQLFAAQRQYGAAWA SPEMEAEYLTILTRQRSF AEGPGGDSPYRGMQKVGP CALEGKSERRAPKATFAF EYFTLLQKINHIRIAENG VNRILTAEERQELLSACY RTDKLDFARIRKLLALPG EARFNMVRYRENQTAELPCHKKKVYKVYKV LNTLRKDHIRSISREQLD AAATALTNPENEEKLRAA LEEAQFEPLEVDALMTLP SFSGFGHISVKACRKLIP YLEQGLNYNDACKEAGYD FQGNYRGEKSQFLPASTE EMEDITSPVVRRAVAQTI KVVNAIIREQGESPVNIH LELAREMSKLAMQLAMQLEMKHEN DLFRGRTITGQTLVKYRL WKEQKEVCAYSLQMMKLD SVITDSSYAEVDHIVPYS RSFDDRRTNKVLVLTSEN RKKGDRLPLEYLQGKRRE DFIVYTKANVKNYRKRQN LLKEGLSKEESREFIQRN LQDTQYSASFMLNYIRH Petition 870250090553, of 03 / 10 / 2025, p. 157 / 262 154 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence LAFADCSAAGKQRVVAVN GAVTAFLRKRWGLSKVRA DGDLHHAVDATVIACTTP SMVKRVTEFCKQEETNHV RNEYFPEPWPRFRDELMQ RLSACPQENLMQINLMQINVASPVYVSPVYVSPVYVSPV HKATGKVHEDTIRSYVSK GITAVRTSITDLKLDEKG EIEGYFNKESDLLLYNAL KRRLEEFGGNAKKAFAEP FYKPRADGTPGAQVRKVK IVDKTSNVICVRDGGGVS KSNNMVRIDVYVPGEGY YWVPIYVADTVKSTNKLNKLNKLRKDDWDKDWKDK FQFSLYNNDLVFIERDSP INFSLTNEKSTLPSKFST ERTFVYYQKGNIANAAIK VKTPDGAYVFNSLTLNTV RKIEKYQVDVLGNYTLVK KEKRQNFPAQRR Efet ores MG17 1 106 Efector MG171-2 protein descondo organism culture MNTAYGIGLDIGIASVGW AVVALNEDAEPYGLIRCG SRVFDKAEQPKTGDSLAA SRREARSTRRRLRRRSLR KADLYALMEXSGLPGRAA VEEAVLAGHLPDIYALRA QALDGPVTAMDFARILLH LMQRRGFRSNRKADDAQK DGKLLQAIDKDNQDNQRMTYFARTHVERTHV CRNKTENYLSTVRRDQIA SEAAQLFAAQRQYGAAWA SPETEAEYLTILTRQRSF DEGPGGNSPIGGNMIEKM VGTCTLEGTAEPRAAKAT WSFEYFTLLQKLNHIRIE EGGNSHPLTHAQRQELLT LCYQTDKLDFARIRKVLDMFPQDQDVRY DACECKKITALPCYHKM Petition 870250090553, dated 03 / 10 / 2025, pp. 158 / 262 155 / 251 Cat. SEQ ID NO: Descrição Tipo Organismo Outras Informações Sequência RKALNTLRKDYILTVGHD RLDAAATALTLYKSEDLL REKLQQADFEPLEINALL TLPSFSKFGHISVKACRK LIPYLEQGENYNDACRDA GYDFQGSGHGEKSILLPA EAEEFSDITSPVVRRAVA QTIKVVNAIIREQGESPV SIHLELAREMSKSFQERA DLENAMKENNADNERLMR DLHELFPGRNISGQDLVK YRLWKEQDGRCAYSLQPL ELQSVITVSGYAEVDHIV PYSISFDDRRTNKVLVLA SENRQKGNRLPLQYLQGT RRDNFIVYTKNNVKNYRK RQNLLKENLSAEDSSGFM QRNLQDTQYIASFMLNYI RGHLAFAAHPMAGKKRVV AVNGAVTSFLRKRWGIAK VRADGDLHHAVDAAVIAC TTDGMIQRVSRFYQRTEL SHARGERFPEPWPRFRDE LMQRLSSCPQENLLTINP VYYTTADIAGIKPVFVSR MPRHKATGPAHKETIKGR LDDTYVTQRRSITDLKLN KDGEIDGYFNPSSDTLLY NALKERLIAFGGNGKKAF AEPFFKPRADGTPGAQVR KVKLYSKATSTVPVHGGN GVADNDTMVRVDVYYIPG DGYYWVPIYVADTVKPIL PNRAVVAYKSCSEWKEMP EENFLFSLCKNDLVCIES KRPIKLKVANEDSTLEKE LTVQRVLAYFEGGNISTG AVSVTTHDNAYIAGSLSF KTLQKVEKYQVDVLGNYT RVKKEKRQLFPAQRR Efet ores 107 Efetor MG171-3 protein a deconh ecido Organismo no MKHPYGIGLDIGIASVGW AVVALNENAEPYGLVRCG Petition 870250090553, on 10 / 03 / 2025, page. 159 / 262 156 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence MG17 1 cultivated SRIFDKAEQPKTGDSLAA PRREARSARRRLRRRSLR KADLYELMEKNGLPGKAE IEQAVQAGHLPDVYALRV QALDGPVTALDFARILLH LMQADRRDAGFRSQNRQKK DGKLLQAIDANTRRMEAN RYRTVGEMMYRDPVFAEH KRNKAENYLSTVKRDQII DEARLVFAAQRQYGATWA SPEMEAEYLCILTRQRSF AEGPGKGSPYSGSNRVGT CTLEGKSEQRAAKAAFSF EYFTLLQKINHIRIAENG QLTZLQLAQLAQLDVKLDFLKLDFLL EARFNMVRYRGEQTAEAC EKKEKITALPCYHKMRKA LNTLRKDHIRNISREQLD AAGAALTNPENEDKLREA LKQAEFEPLEIEALLTLP SFAGYGHISVKACRKLIP YLEQGMNYNDACQAAGYD FQGRQNGEKAQPASTE EMEDIQVRA KVVVEQVESVIQVS LELAREMNKNFQQRSELD KAMRDNSAENERLMKELN ELFPGRTVTGQDLVKYRL WKEQDGRCAYSIQPLELD KVITVSGYAEVDHIVPYS ISFDDRRTNKVLVLASEN RQKGNRLPLQYLQGKRRD DFIVYTKANVKNFRQRQRQRQRQLLKYRKYRG LQDTQYIAAFMLNYIRNH LAFADCSGAGKRRVVAVN GAVTAFLRKRWGLSKVRA DGDLHHAVDAAVIACTTQ GMIKRVSDFCKRAETTAV RNEHFPEPWPHFRDELTQ RLSACPQENLMQINPVYY Petition 870250090553, of 03 / 10 / 2025, p. 160 / 262 157 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence ATVDISSIQPVFVSRMPR HKVTGAAHKETIKSRLDD AHTVQRRSITDLKLDKEG EIAGYFNPSSDTLLYNAL KEQLTAFGGDGKKAFAEP FFKPRADGTPGAQQVKVKVKVAGVKVAGVKVAEP DND™VRIDVYFVPGDGY YWVPIYVADTVKLKLPNK AVVQGKSYAEWKEMDEEN FLFSLCQNDLIRIESKRT MKFKVQNSDSTLEKEAQM NCRLTYFEGGNISTGAIT VTTHDNAYIVGSLGFKTL QKIQKYQVDVKKKRRQRQTLQTLQ17TEFET 1 108 Effector MG171-4 protein a desconh acid Organismo não cultivado MKHPYGIGLDIGIASVGW AVVALNENAEPYGLIRCG SRIFDKAEQPQKGDSLAA PRREARSARRRLRRRSLR KADLYELMEKNGLPGKAE IEQAVQAG VHLPDVALDRIVALDHALL LMQRRDFRSNRKADDAQK DGKLLQAIDANTRRMEAN RYRTVGEMMYRDPVFAEH KRNKAENYLSTVKRDQII DEARLVFAAQRQYGATWA SPEMEAEYLCILTRQRSF AEGPGKGSPYSGSNRVGT CTLEGKSEQRAAKAAFSF EYFTHIFTQENQERGVRTACLL QTDKLDFARVRKALPE EARFNMVRYRGEQTAEAC EKKEKITALPCYHKMRKA LNTLRKDHIRNISREQLD AAGAALTNPENEDKLREA LKQAEFEPLEIEALLTLP SFAGYGHISVKACRKLIP YLEQGMNYNDACQAAGYD FQGRQQQFLQAST Petition 870250090553, dated 03 / 10 / 2025, pp. 161 / 262 158 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence EMEDITSPVVRRAVAQTI KVVNAIIREQGESPVSIH LELAREMNKNFQQRSELD KAMRDNSAENERLMKELN ELFPGRTVTGQDLVKYRL WKEQDGRCAYSIQPLELD KVITVDVSGYVSGYS ISFDDRRTNKVLVLASEN RQKGNRLPLQYLQGKRRD DFIVYTKANVKNFRKRQN LLKERLSEEDGKGYIQRN LQDTQYIAAFMLNYIRNH LAFADCSGAGKRRVVAVN GAVTAFLRKRWGLGKVRA DGDLACHAVDAQVSTKRAIKVKRAIKVFKRAIKV RNEHFPEPWPRFRDELRQ RLSACPQEDLMKINPVYY ATVDISSIQPVFVSRMPR HKVTGAAHEDTIRSQVNE KYTAVRKSITELSLDKDG KIKDYFKPSSDTLLYEAL KKRLTEFGGNAKKAFAEP FYKPRADGTPGAQVRKVKVKVKPVKGMMNNGVAEP KGGDMIRIDVYVPGDGY YWVPIYVADTVKETLPNK AVVRDKTMEEWKEMKEDD FLFSLYSNDLILVERDKP ICFSLMHEDSTLPKKYET KKELVYKGGDISNGGIR IETHEGAYFLKSLTFGIV QKVQKYQVDVDVKRRKGRPQQRTPVQRES MG17 1 109 Effector MG171-5 protein a desconh acid Organismo não cultivado MKHPYGIGLDIGIASVGW AVVALNENAEPYGLIRCG SRIFDKAEQPKTGDSLAA PRREARSARRRLRRRSLR KADLYELMEKNGLPGKAE IEQAVQHLAVQHLDAVQHLDVALDGALDHALL LMQRRGFLSNRKADDAQK Petition 870250090553, of 03 / 10 / 2025, p. 162 / 262 159 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence DGKLLQAIDANTRRMEAN RYRTVGEMMYRDPVFAEH KRNKAENYLSTVKRDQII DEARLVFAAQRQYGATWA SPEMEAEYLCILTRQRSF AEGPGKGSPYSGGGGTKTFQTQATFQA EYFTLLQKINHIRIAENG TSRTLTPAERQVLLSVCS QTDKLDFARIRKALPE EARFNMVRYRGEQTAEAC EKKEKITALPCYHKMRKA LNTLRKDHIRNISREQLD AAGAALTNPENEDKLRKA LEQAEFEPLEIEALLTLP SFAGYGHLIGHKVACQLEIQQLEQAGM FQGKQNGEKAQFLPASTE EMEDITSPVVRRAVAQTI KVVNAIIREQGESPVSIH LELAREMNKNFQQRSELD KAMRDNSAENERLMKELN ELFPGRTVTGQDLVKYRL WKEQDGRCAYSIQPLELD QVITVSGYAEVDHIVPYS ISFDDLARTVLVLDRSEN RQKGNRLPLQYLQGKRRD DFIVYTKANVKNFRKRQN LLKERLSEEDSKGYIQRN LQDTQYIAAFMLNYIRNH LAFADCSGAGKRRVVAVN GAVTAFLRKRWGLSKVRA DGDLHHAVDAAVIACTTQ GMIKRVSDFCKFRETTAVPHRAVHFPDELTQ RLSACPQEDLMQINPVYY ATVDISSIQPVFVSRMPR HKVTGAAHKETIKSRLDD THVVQRRNITEKLDKDG EIAGYFNRSSDTLLYNAL KARLLAFGGDGKKAFAEP LYKPRADGTPGARVQKVK Petition 870250090553, dated 03 / 10 / 2025, pp. 163 / 262 160 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence ICDKVTSTVPVHGGKGVA DND™VRIDVYVPGDGY YWIPVYVADTVKPELPSK AVVAYKSSAEWKEMKDED FLFSLCQHDLVRIESKRL MKFKVQEMHREKHREKVGTEGVTLGATE LTTHDDAYIATGLGFKTL QKVQKYQVDVLGNYTPVK KEKRQTFPAQRR Effect ores MG17 7 110 Effector MG177-1 protein a desconh acid Organismo não cultivado MQYRLGIDLGTNSIGWSA VLLDEEGKACGLLDMENGSPLGGSQSPLG LAVNRRIPRGQRRRRDRY LRRRSELLDTLTACGLMP PDAESRAQVAALDPYPLR CLALEQQLSPYDLGRALF HLNQRRGFKSNRKARPKD DEKESRENLTNLRIALRE NDMQLGEYLAELHAQGKP VRARPGLDLYPDRAMYEA EFDAIRKEQEQPQPQLQLDHLRQLDHLRQLQLRIALRE DPGWCLLEEGERRAPRAL HSAQEFRILQELNNLRTR VGIEPERPLNDAERSRML QRLREGKEVDLQKPPKGL RLDGSLNLSRGGRKKKLQG DQTTVRLTKPDLFGERWL SLTPEERDAIVERLLDTE DPEAVRQTAVSEWDLSEA QAQKEVHLDVHLVHLKLVKHLDGLV EAVVKAGYPHHSDFRNAE AHDRLPYYGIVLQRDVVG ADPNAPEADEAKRFGRFP NPTVHVGLNQLRRVVNRL IDAYGKPADIVVELARDL KSSKEQREEYVRRQRSNE HENDRRRKELQECGIEPN GYVMEKLRPWEEQGPVQA RLSFTPPISDGGYVGR Petition 870250090553, dated 03 / 10 / 2025, pp. 164 / 262 161 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence ATEIDHVLPRRTLDDSLA NKVLCLREVNRFKSNRSP HEAFHDSPFGYDYDYDSILA RAEQLPDNKKWRFLPDAM DRFADESGFLERQLNETR YLSRTARSYLAHDLEFARGVIRGGMTVIRG RGWGLEGMLRESGGGKQR DDHRHHAIDAFVAANTTQ GLVQRFQQQAAGSVEPEAR LAKLLGREELKPWPGFDC SEVKPLIDRMTVSHKPDH GALGGGKTTGQLHKATA YGLLEEPGNGPSRVVIRM NLAAVVKRADLAAVRDPG LPEWPEGELLW LDRAEEELARREDRRPQK QPVGAIFAERAGDEEVGV SVNGHIQRVRRVRIVEEQ SVVPIRDSTRKAYKGYVR GSNAFADVWRTPDGSWKT VVVPTFEFNQQDFTIENF RPASKDGRPDPTAKRLMR LHIDDMGAFGEGADRRIV RVRKISSAT GALDVANQVAN ENKYSAKQLREQGFRRVG VDEIGRVLDPGPRTG Efet ores MG17 7 111 Effector MG177-2 protein a desconh acid Organismo não cultivado MKVINRSKYRLGLDLGTN SIGWAAVTLDDQGRPCGV LDMGVRIYPDGRNPTDKRRVRRQRRQRRGRR YLARRGELMQALMEFGLM PPDAEAREELQRLDPYSL RARALAEPLHPFELGRAL FHLNQRRGFRSNRKSDGE GEEDRKKLGTAIEGLRLR IQESGARTLGEFLARRHA QKETIRAREELGLYPERT MYEEEFDAIRQEQGEHHN LSSEQWDMLRNIIFQRPHQRFEQRFEQRFE Petition 870250090553, of 03 / 10 / 2025, p. 165 / 262 162 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence RAARALPIFQEFRILQEV NNLRVQVGSEQGRPLEKE EREGALKRLRSGKDIDFR KPTRDLRLPSDVSFNLAR GGRQKIKGDEVTGRLSKK DLFGSLWRGLSKLEKDLTEVLLKLDVLLK EEWALTASQAKAVAAVFL PTGYGDLSEKAIRKILPH LEKGSLYSDAVREAGYSH HSDFRSDAALDCLPYYGE ILQRDAIGADPTKDPVKD GEVARYGRFPNPTVHISL NQLRRVVNRLIEVYGKPG EIAVELARDLKSNHEQRL TYQRRQREQERQERQERQERQERQERQEMLARKLREML LWGEQGDPQARVCPYTGR NLSFVMVVSSQTEVDHIL PFSKTLDDSMANKVICVA AANRDKGDRAPYEAFGHS PPGYDYQKLLDATAKFPP NKRWRFREDAMERFADEA IFLDRQLNETRYLSRTAR AYLAHLYDEKGEGRRCVL ATPGHLTAWRTAQTGLTGLEGLAVRGLRGE HRHHAIDAFVVANTTERL LQRFARATASSSHHTAAEK LGSLVPDPWEGFHHEQLR PILDRLAVSYKPDHGTRG VQGKTTGQLHNDTAYGLV ELSEDGPSRVVRRKKLSA LKRRSELEAVRDPDMRKA LMELWEQVDSEIQAEGK ATPAEGVGK LGGRRQIVRRVRVLEKET VMPIRDRSGRPYKGYKRG GNEFADVWRMRDGSWKMV IVPRFEANQPGFDLESFR PTDKSGRKDPTAKRLMRL QINDMGAIGEGEERRIVR Petition 870250090553, dated 03 / 10 / 2025, pp. 166 / 262 163 / 251 Cat. SEQ ID NO: Descrição Tipo Organismo Outras Informações Sequência VRKMTATKTRNLVFLDEH NEADVPSRIARKELKEHK YSARQLQRSGFRKVGVDE IGRVLDSVPLRS Efet ores MG17 7 112 Efetor MG177-3 protein a desconh ecido Organismo não cultivado MKTTRDKRYRLGLDLGTN SIGWAAVNLDDQGQPCGV LDMGVRIFFDGRNATADK TSNAVARRTARGLRRRRD RYLMRRDELMQTLIEYRL MPPDPETRKELQRLDPYS LRARSLDQPLSPFELGRA LFHLNQRRGFKSNRKSGG EEEDERKKIGPAIEGLRR SIDESGARSLGEFLARRH AQRETVRAREEVGLYPDR AMYQEEFDTIRQKQEEHH KLSPEQWDRLHDIIFYQR ELQPVKPGWCQFEFTSEE RRAPKALPIFQEFRIFTE VNNLKVQIASEPERPLDP QEREGVLKRLRSGLDISF KNPTAGLKVPSLSSGVSF NLARGGREKIQGDVVTKL LKKKELFGSRWLSLSLKK RNEIVKTLLLVEEPETIQ LKAIREWGLTESQAKAVA NVSLPTGYGDLSEKAIRK ILPHLEKGRLYSDAVKDA GYSHHSDFRSSSALDRLP YYGEVLRRDAVGADPTKD PQKDGEEARYGRFPNPTV HIGLNQLRRVVNCLIEVY GKPEEIAVELARDLKSNL EQRLRDQRQQREGRERNQ RYAETLEAKGLESTPDLR RKLRLWEEQKQGAVCVCP YTGRTLSFAMVVDSQTEV DHILPFSQTLDDSMANKV VCIAAANRAKGDRSPYEA FGKEILDRTTNFPPNKRW RFGPDAMERFEQEDRFLD RQLNETRYLSRTARAYLA Petition 870250090553, dated 03 / 10 / 2025, pp. 167 / 262 164 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence HLYDEKGEGNQRVWATPG RLTYLLRRAWGLERILRA DTDTGKIVRKQRDDHRHH AIDAFVVANTTQGLFQRF SRTAASGHHTAVERLAAL VPDPWEGYQREQRLVLDVKLKVLRGVWGLRGVWATPG TTGQLHNETAYGLLEPSE DGPSRVVRRKKLSAFKKK SELDDVRDPDMRKALIDL WDQTAAVIQAEGGKVSET PMRFAERAANEGVLVGGR RQTVRRVRVCEQETVILI RDQAGEPYKGYKRDGNEF ADVWRMRDGSWKMFEKFREKQPREKVDFPNDFPK AGRKDPTAKRLMRLFKND MGAIGEGEERCIVHVRHM GTKTDRGPYVVLDDHEEA NVDRRRRRGEIKEISYGA RKLQRSSFRKVGVDEIGR VLDPGPPRL Effect ores MG17 7 113 Effector MG177-4 protein a desconh acido Organismo não culdo MKYRLGLDVGTNSIGWWC VGLDADGAPAASIGGGAR VFSDGRNPKDGESLAIQR RTPRAMRRRRDRYLARRS DLMDALIATGLMPADEAE RQALVRLDPYELRAKAVN GAAKPHELGRALFHLNQR RGFKSNRKTDEPDDKSKI QPRIIELKKRQRRQRQLGLGGLGVR PEAGFYTDRSLYEHEFDK IREVQAPHQTLRPEQWDE LRKIIFFQRNLRPVDPGW CLLEKGERRAHRALPCAQ EFRMVQETNNLRILAPGE PAKPLTREQRDRVLKELR TRKKLELDTLLKLLKLPS GARINLLDENRKALKGDE TAARMREKLDQTLEQEMPEQEMPGLIPG Petition 870250090553, dated 03 / 10 / 2025, pp. 168 / 262 165 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence IERVAQDEWGLDETAAKK LSHTGLPDGYARLSEKAI NKLLPVMEEQGLVYADAV AEIPEYGSHSDFRSSRAL DRLPYYGAVLERQCVGGD PTKPKEDEVAHYGRLANP TVHIGLGQLRRLVNRLIE TYGKPEEIVIELARELKM NKEEKDKERQKNLKNKEA NERREKDIRAAGGAPTPH LLRKLRLWEEQKYGAENV CPFTGSPISFSMAINEST EIEHILPFSKTLDDSMAN KVLCLREANRAKKDRSPY DAFHANPTIGGRTYNYEE IKMRADALPPNKRWRFYP DAMEKFADEAKFLDRQLN ETKYLSRIARFYLSHLYN EKDEQRLRVRAIPGRLTA MLRGKWGLNALLSDHNRL GGDGDGDDRPRKNRDDHR HHAIDAFVIAMTDQRLLQ RISAMNSDADRKRLIDQM PPPWEGFTPDILRPQLER LIVSHKPDHGTFPWMAKT KSAKGKSQTSGSLHNDTA YGLIAPGKNGSGNVVWRK SLASLLTPKDMDAWLPRV RDHALREALIAEWKTFKN AKPSATEKPLEESNRKKK NAAGLFAEHAARVGVQLN GRKVKVRRVRVTDDVGVV PIKERKTGKPYKAYRPDG NAFADIYQLPDGSWKTVI IRRFDANQPHYNPATERP HPAAKKLFRIQIDDLCAI YQNEERRIVRVCKLSTES GKEHVYLIDHNESNVDAR VRDKELKYFKESASSLKK KGFRKVGVDEIGRVTDPG PRTGKTG Petition 870250090553, dated 03 / 10 / 2025, pp. 169 / 262 166 / 251 Cat. SEQ ID NO: Descrição Tipo Organismo Outras Informações Sequência Efet ores MG17 7 114 Efetor MG177-5 protein is found in the Organismo no cultivado MNDQQTAPYRLGLDLGTN SIGWAAIRLDANNDPCGI LDMGVRVFPDGRDAKSKE SNAVTRRVARGARRRRDR YQKRRADLLRRLTEYGLM PADNGERKALAARHDPYE LRARALDDPLSPHELGRT LFHLNQRRGFKSNRKADQ DSGESGVIREASEALEAQ MAESDARTLGEFLDHQRR AGQPTRFRNLSSGATAKY EFYPTRQMLLDEFDQIRT AQETHQTLCPEQWDVLRD QIIFFQRPLKPVDPGWCQ FEEGEQRAARALPVAQEF RLLQEVNNLRIRVGIEPE RQLNTEERARALERLRSG KDINLAKPTRDLKLPSQT AFNLSRGGRSIVKRDETT DRLISKKERGKPRQDIFG DRWRNLSLDQRNQIVRFM LDTDDPAGVQRKALTDWG LNETQAKVISDLGLPDGY SNLSEKAIRKLLPHLESG LFFSDAVQAAGYKHHSDF RSAEAHASLPYYGQVLQR DAIGADPTKDPAIHGEPA RYGRFHNPTVHIGLNQLR RVVNRLIEVYGKPEEIVV ELARDLKSNHEQKRRYQQ QQKEGEERNQRFDEMLQS AEQESNPLIRRKLRLWEE QGPAQARVCPYSGRVLSF EMVVSSQTEIDHILPFSQ TLNDSMANKVVCTAQANR DKGDRSPYEAFGYNPTGY NYDDIQARAAALPDNKRW RFDPDAMQEFQENRDFLD RQLNETSYLARTACLYLA HLYNEKTEGRRLVRAIPG HMTYVLRRGWGLEGMLLRV TPAGEIVRKQRDDHRHHA Petition 870250090553, dated 03 / 10 / 2025, pp. 170 / 262 167 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence IDAFVVASTTQGLLQRFA HASRSRRQEAAERLAAIA GDVRPWDGFSREELQPFL DGLVISYKPDHGNRGQSG HTTGQLHNETAYGLVGLS ESGPSEVVEKTALKPLKDLVKDLVKDLVPTVR ALRVALLKLWDEVRGKTT EFAERAATEGVRRINGRIQ RVRRVRLLDQQRVIPIRD VTDKPYKGYLPGGNEFAD VWRLRDGSWRTVAVPTFD ANQPEFDIELFRPSDKIT GRPDPAAKRLMRLHIDDL GALGEEQSRRIVRKIT NAKAGVNEDHFLDHVLDLGVNRVDRVDRVDRVDRYD QRFGFRKVGVDEIGRVLD PGPSNR Efet ores MG17 7 115 Effector MG177-6 acid desconh protein Non-cultured organism MRYRLGLDLGTNSIGWWM VELDKDGIPCGSLGGGSR IFSDGRNPKDQSSLAVER RVPRGMRRRLRMDRELGDRALDRALDRALGDR RKALEGLDPYALRAAALD RGLRPHELGRALFHLNQR RGFKSNRCTDSSEDDKES GIVKERIGELHRLMEKAN ARTLGEFLHKRHLKGRMV RARPEAGFYPDRKMYEDE FDAIHTTQGSHQTLRPEQ WEALRDIIFYQRPLRPVD PGWCLEGLEGRALQLQLQLQLQLV PGEPARRL™TERNKVLE HLRTKKELKLEGMLKLLK LPSGSTVNLFDDHRSLLK GEETAARLTHKDIFGKAW FDLSMERRTEIVRKLLDI EKPEEIERIAQAEWGLDE AAAKKLAGKALPDGYARL SEKAIARLLPIMETQGLN Petition 870250090553, of 03 / 10 / 2025, p. 171 / 262 168 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence YAEAVAEVPEYGHHSDFR PDEARDFLPYYAEVLSRH CVGADPSKPKEDETAHFG RLANPTVHIGLNQIRRVV NRLIKVHGKPEEIVVELA RDLKMNKEQKDEARRRREAKNREAKSIRAGV APSPHLLRKLRLWEEQKV GTAHLCPFTGDAISFEMA IGAATEIEHILPFSRTLD DSMANKLCLREANRAKR DRAPHEAFQNNPTIGGRK YVYDDILFRADKLDGNKR WRFHADAMERFESEERDF LDRQLNETKYLSRIARSY LSHLYNEKAEGLRGLRGLGLRGLR PGHNRAPAPDAPPRKNRD DHRHHALDAFVIAMTDQR LLQLISQLNADADRKRLI DAIPEPWEEFDREVLREQ LARLTVAHKADHGTPGKM GKTTGALHNDTAYGIVGP GKKGNTQVVYRVPLARFA TPDALDKSLPSIRDVALR HSLIAAWEAFKLAPDKNPDFPKNPDFPKNPDFDREVLREQ TEMVASDGIEIGGRITKV RRIRICDELGVIPIKNKK TGEPYKAYKPDGNEFAEV WALPDGSWRTVIVRRFDA NQPGFDTTNLRHHDDPDQ RLHPAARKLMRLHNGDMG AIGEGAERRIVRVCKMST ENGKEYIYLADHNEGNVD ARKELKVRKLQLQLQLDKVKGVKGVKVK PGPRASSGPQAA Effect ores MG17 7 116 Effector MG177-7 protein a desconh acid Organismo não cultivado MSSSVVNYRLGLDMGTNS IGWAAIKLDEQGKPCGIL DLGVRIFPDGRSNPKDST SASNAVQRRLARGGRRVR Petition 870250090553, dated 03 / 10 / 2025, pages 172 / 262 169 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence DRYLMRRSKLLNALVQYG LMPSDPEGRKRITADEKL DPYELRARALDRPLNPFE LGRAIFHLNQRRGFKSNR NASGDNDNEAKQTRDAIS ELHRRIEESRSRTLGEYL HRRRKKRKPVRARPDLGL YPDRALYEQEFDAIRAVQ QLHHAMNDVQWENLRETI FCQRPLKPVKPGWCTFEE GEHRAARALPLFQEFRML QELANLTLHVGAESERRL SDKQRACTLERLQAGDDL NLDADKHKRIKNTLGFPS DTNFNLVAGIRTILKGDE TTAKLRKPEMFDRKWLVL SLEERNDIVKFLIKTDDP EVVREKAVVEWGLTEEQA VAVSNVSLTSGYGNLSEK AIRKILPHLEIGKGYSEA VQAAGYDHHSDFRSEEAH DNLPYYGEILPRAVVGAN PDKDPKSDGEAAHYGRIA NPTVHIGLNQLRRVVNAL IKTYGKPEDIVVELARDL KTNREQKRRDDQRRREGV DRNERLTEMLKSAEQSVS GEILRKLRLWDEQKKGSL HICPYTGRNISFEMAVSA QTEIDHILPFSRTLDDSM ANKVVCIAAANRAKGNRT PYRAFGDNPPGYDYERIK ENVANFPHNKRWRFQPDA MNRFEGENDFLGRQLSET RYLSRTARTYVAYLYDQR GEGKQRVRVIPGHMTALL RRGWGLEGMLSDNPDGEP VRKQRDDHRHHAIDAFVV ANTTQGLFQEFSRAAGSS YQNAEERLASLIPPPWNG FDINELKQLLDNIVVSYR PDHGTRGAEARGATTGQL Petition 870250090553, dated 03 / 10 / 2025, pp. 173 / 262 170 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence HNDTAYGIVELVEDGQSA IVVRKPLSSISRKALNDV RDTHLRAALINLWDEVGG NKARFAERAWSEGVEVNG RRQKVRSVRVKGNLRIIP IRDRVGNAYKNEGYLPQVGVGVGVGVTLRIIP TFDANQPDFDIEKFRPTT SRGQYKGKPDPAAKRLMR LQIDDMGALGEGTERRIV RVRKITNNARQGGLVVLD DHNEANVPERVTRDARIR KDSGIDIGMKEEVYPASK LRRFGFRKIHVDEIGRVR DPGPKSS Efet ores MG18 3 1 Efetor 183 MG18 ecido protein descondo Uncultured Organism MAYRLALDLGTSSIGLVA VRLDGNVQPTEIIYHACR IFAEPLDPSKKGGVGEPK KARRRKARLARKLIDRRS RRLKRIAALAELIGLNPA TVDADDGQSLHRLRAEAA TRAILLPDLLRVLLRMAK RRGYSGGFKTKREGGISKKEMKAKKL DFLGQYLYHRFQNGQTLK LKEAGLYADRAMVEAEFD RIWDIQSQHHAVLNGSHN GEPLHKIFREAIFYQRPL KSVAGMVGNCALEPSLPR APMCQPAMQAFRIEKQLS DLRWGTGRRAELTLAQRD VIRGLLGEKKEVPFSAIG KALQQNFSAIGKDDQALKNF DRTSRPALRGNGTAAAFD KLGLLNAWRTLPVGVQVS TLNFLADLGSPQEVDRSD WHKKYARKDGNPREFKPE MVAFINKLVDSGKFDRLS KMGFDGGRAAYSIKALNK LTEWLRAPWWPEDWKGDK TVSEDNAIRACYPDGMRKSTQLKVSLGVSLKV Petition 870250090553, dated 03 / 10 / 2025, pp. 174 / 262 171 / 251 Cat. SEQ ID NO: Descrição Tipo Organismo Outras Informações Sequência VDVALRQLWHQINVCIEK LGEPPAEVIVELTRDMGL GVKRRNEIEDRINKNRRS RQDAADKLSAHGESATDR NIFRYLLWQQQETSCPYC ETKIGLHEAVSGGATNIE HIVPRSLTRVGRQRDHLV LAHRQCNDEKGDRTPWQA WGGDADRWAQIEAHAKVL EKKLFTKARLLTIKDYE GEVLDDSAIEGFSERQFH ETSWIAKLAAQWLRAVCQ NVAVSRGELTAFLRRIWR LDTVIPEVRFEENLPVLD TDKNPVTHDEFDRFRRCW EGHDRDPAAEQTDRKIDK RIDHRHHVIDALVIAMTT RGLYQKMARHWKAEREAG RKPSLSIPPLMRNLREQA LELVRNCNLTHKTDHYPA GKFFKEHAYRRVLMDNDK KRLVVRAVLASLVDNKTS LDKARKAISDIVSDEVRN IVSDEFDRRTARGMSPQE ALSSPIAYPRYRDRKNGR EVIIKKVRLYQRMGRGYA DGEDAVPIIHTQRQGKEL LKHYLSDGYAYVSLKFDN GRLVSAESVPLYVAPRRS ARPEPGETRYYTNDTFQD TSTNRRYVVRQIRANAAL ALTLVSEAREVRDLDADA GLMVVSGNGLLRLAPA Efet ores MG18 3 118 Efetor MG183-2 protects the device from the organization and cultivado MKYRLGLDVGTASVGLVA LELDGDDRPVKPVWHSVR IFDEPLLQAKRGGVGEPK KAARRLARQQRRGYERRS RRMKRIAHLARLMGLDPE TIESDKGQRIHELRDSAV TSEISLPDLLRVFLVMGK RRGYAGGFKAKKGKDNGQ VETGIGNLKTAMREHGCE Petition 870250090553, dated 03 / 10 / 2025, pp. 175 / 262 172 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence TLGQYLWSRIQHGQHLRL KDDGLFADRQMVEDEFNR IWKTQEKYHQILKKHYNG KPLQNFFYKTIVEQRPLK SPAAMVGNCSLEPMLPRA PMAQPVMQAFRIEKQIAD LRWGTTRRAQQLFPEQRE VIREQLQDKKEAKFTSLY KELKKAGCPPGPEERELNL AHGDREALTGDRTAAAMK SLNLLEKWRELTEGHQLS VINLLADMGSPEAFDAPD WDKKLKGSNGVERKIKPE VKHFIDEMLETGKFDRLA KMGFDGGRAGYSIKALRK LVATMRERGVDEHGAIAL AYPEAHKSNPELLGKDMQ RSEALSAHRETGSTVVDV ALGQVRQEVNAAIARLGT PPSEIIIELSRDMKTGLK ARDESIKRMRANEKRRRE AACEIEKLTTRSATQSQI RRYLLWKEQGEKYCPYCT DPINLSDVINGNETEYEH ILPQSLTRIGKKRDFLVL AHKACNQAKKDKTPWQAW GQDEERWRIIEHRAEQFK HKGKARQLLIRDFESEAL DDDVINDFTDRQFQETAW IAKECGKWLRSICSNVFV SRGLLTAHLRRTWGLDTV IPEVRYEEDMPVFDDDYQ PNKKESDQTACKVSKEDF DRYRSHWEGHPVSKDNRI HRRLNKRIDHRHHLIDAL VIALTSRSLYQRMAADYK KVSDSGPKTLRLYAAPEL KDIRRRALELVRTCLPSH RPDRWLAGNMFKENPSAI REENGKRFYAQRKMLKGL SEKDIENIVPQSLRDVIR TTFEQRIRAGKTPEQAWK Petition 870250090553, dated 03 / 10 / 2025, pp. 176 / 262 173 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence DILHPQYKTPIRRVLIRK NAAQDAVRVEHGNRKTDL YKYLEPEGYVCLEFDSED ADAEPRLIRLHEAMKPER QRRSSLNVVRFYKNDTLY DARDEKHYVIKQIQLDKVIGKVIGKVIGK SSPRQKKVSGKQIKKLKL VKDGRQSNFAG Effect ores MG18 3 119 Effector MG183-3 protein a desconh acid Uncultured organism VKYRLGLDVGTASLGLVA YKLDAQGRPVSIPYHSVR IFDEPLLPPGQGAGGARGQLQQLQHRRQQQRQ ARRLRKLAHLAHLLGIDP EAVARRRKPHILEVRARA ATEKVDLEDLLRIFLHLS KRRGYAGIFRAGKGGDMG QVQTGIGDIRKKMDEAGC ETLGEYLWHRQGQDLR LKGHGLYADREMIFNEFD RIWARQEREHKQLCGEHK GLPFEKFELFERFILESPRISPRISP LVQPAYQEFRIEKQIADL RWACKGRRHPKPLEEPAK QVIRKLLSENERVKFEEI YKALEKTGIPPAPDEYLN LSEGGREDLHGNVTNACM KKLGLESEWQSLTDGHQI AALNLLANTGSPDIFYAR NWHENIPKGKKRADGGTKVKVKVKVKVKFEEI YKALEKTGIPPAPDEYLN EKLDWLSKMGFQAGRSPY SIKALRRLTAAMREQNLD EADAKALLYPRAAKAVSR GEMQGELPPHQHTRNVVV DVSLRQVRREVNAAIRKL GGPPDSVIIELSRDMPLG VKRRGEIVDGINKNQRAR QKAAREIEKETGKAASNV AIMNYLLWREQDEQDEQDQALDQDKDQDKDKDKDCLPD Petition 870250090553, dated 03 / 10 / 2025, pp. 177 / 262 174 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence HIIPRSITRIGKSRNYLV LVCHSCNDEKGARTPREK WGDDPERWKVIEKQAKRL GKKKLLGKMRQILSRESG ESLLDDEAIGDFSARQLQ ETSWIAKSCAQWMGMICS NVAVSRGILTESLRRKWG LDTVIPEVRLEKKLPVFD REKQLITPEDFERHRAYW EERGEEGDSGKTHRRIDK RIDHRHHLIDALVIGLTS RGLYQKMAQAYKREAERT ASPADRRSIPLRAKTPIA DIRNLALDLVRNCNLTHK RDRWPAGPFFDLNPVSIY EGQFSQRWELTKLAKKLS DKVSDNPEKRAKDLAAGL KQINKIANPSTREIVRRA YEERISTGKSPKQALSMP ILDMRFNKRFGTQIRRVL VRYDEKAKGQITVKHGRN GELKKYLKTEGYAWLEWD AQKGEARLVTLYEAMKSG RSEAPKGVRFFKGDTVLN ASDEKRYVVRHIKAEKGG CLVLILHTETREVKHMDS DSGKKWVSGKNLSKLSLI SDDWPPHSSE Efet ores MG18 3 120 Efetor MG183-4 protein is found in the Organism no culture VKYRLGLDIGTASVGLLA LELDNKDRPVRPVYHSVR IFSEPLLPPKSGGVGETK RSARRAARQQRKGHMRRA RLLERIAKLASSMDVDSA NIPPDKGQRIHKLRAKAA TSEICLEDLLLVFLNIAK RRGYYGGFKIKKDKEAGQ VESGINNLRETMRNHGCS TLGEYLWHRIQHGEHLRL KEVGLFADREMIENEFNR IWNTQEKHHPVLKEEYNE KPLREHFYKAIVMQRPLK SPAVMVGNCSLEPMLPRA Petition 870250090553, dated 03 / 10 / 2025, pp. 178 / 262 175 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence PMAQPLMQIFRIEKQIAD LRWGTTRRAEPLSLQQRK VIRKQLHAKKEVKFSALY RELEKNGCPGPEGRELNL TFGDRQSLTGNRTVAAMK SLNLLTQWNALAEEHQIN VISLLAEMGSPEVFDMPE WDKNLKGAKKVQRRNIKP EVKGFIDEMMSTGKFDRL SKMGFDSGRASYSLKALK RLVSIMQKDNADEYTAID QAYPHTQETTQGELEKDL PPHQSTGNVVIDVALGQV RREINAAIAKLGGPPHQI IVELSRDMRMGLMQREKS IKRMRANEKRRKEAALEI EKHLPFKTATESRIRRYL LWEEQGKKYCPYCERHIN FSDALNGNETNYEHILPE ALTRIGKKRDFLVLAHNG CNQQKKKKTPWQAWGHNE ERWNIIKDRAEQFEKGFG TKNFRHKGKARQLLIKDY ENEALNDEIIGDFVERQF QETAWIAKACGKWLRSIC ADVSFSRGILTAHLRRIW KLETVIPEIRYKEDMPVF DEDYQSNKLESKQTECEI TEEDFDKYRPYWEGHRNK NTLRTHRRLNKRIDHRHH LVDALVIALTTRSLYQKM ALHYKQVTESGEKKLRLY AEPEMKDLRKTALGLIHD CQPSHRPDRWLGGNMFKD KSSVVIEENGERIYAQHK NLADLALGNTGNVVSVDT VRNRIEKIMCDKTRGEVS KEFESRLKEGCDFRLALE KIYHPHWNTPIRRVLIRG NKAVDPKPIKHGNRAMNL QKYLEPTGYAYLEFTRGN SNSRPRLIRLHDAINREA Petition 870250090553, dated 03 / 10 / 2025, pp. 179 / 262 176 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence PSPGTVRLYKQDTVLDSK DQQRYVIQKFIADGPSLF LSPVTEAIADVGKVRGKR QRKVSGKKIIERLTLIED ERA Efet ores MG18 3 121 Effector MG1835 is the Organismic protein uncultured MDANTAIWGCQVKYRLGL DIGTASVGLVALELDGG RPVKPVHHSVRIFDEPLL PPKSGGVGKTKKSGRRVH RQQRKLHMRRARRLQRIA QLAPLMGLDPKTIPADKG QRVHKLRAQAATVEIPLE DLKVRRGFLYGLLYGLL FKVKKSGDTGMVEIGIGK LKAEMKKAGCGTLGEYLL HRIQNGQHLRLKEEGLFA HRDMVEEEFNRIWDVQEG RHEKLRDEDLRKDFHKVI VLQRPLKSPAHMVGNCSL EPMLPRAPMAQPIMQAFR IEKQLADLRWGASSRAEPRAEPREQLTAQL VELPALYKVLEKSGCPGP QGRELNYERGDRQVMTGD RTAAAMKWLGLLQDWNAL DAGHQISVINLLADMGSP DAFDNPQWAENLVGAKVG ANKTQRNIKPEVKHFIDQ MVTTGKFGRLSEMKFDGG RASYSIKALSKLGLDEPHREPDHE GTKLEKEKELPPHPSTGN TVIDVALGQVRREVNAAI KKLGTPPSQIIVELSRDM KVGLTKRGKINDKMRANE KRRREAAGTIEEHTRKAA TESQIRRYLLWQEQGEKY CPYCERHINKLSDALNGN ETEYEHILPSLTRIGKKKH RSCVEKKKH FLQN TPRQAWGHDEERWNIIER RAEQFEKGRKITIAGKER Petition 870250090553, of 03 / 10 / 2025, p. 180 / 262 177 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence TLFKRPGKARQLLMQDFE NEALSDKIIDNFTDRQFQ ETAWIAKACGKWLRSVCA DVSFSRGLLTAHLRRNWK LDTVIPEVRFEEDLPVFD EDYRSNTKESSQQKWEKWEGKHKHKHDGGHD IPRTHRRLNKRVDHRHHL VDALVIALTTRRMYQRMA KHYKQVTDSGKNSLRLYA EPGIKGICALLDMVREC QPSHRPDRWPGGGFFKDN PGAIVEENGERFYARRKK LTDLGKTDMDKILPESVR EIVGNAYKSRIQKGADHE SALKEPIRHPHPHPWTPH VLVRRNKAEDDVLIEHGD SQRIQGKAADSKSSSLHKY LEPDGYAYLEYIPGDLTT EPRLVRLHEAKSTSSQTV RLYKKDTVRDSQDERRYV IHQIMAEGPALFLSPVTE SIADIKVRGNRKRKIFG KQIAKRLTLVKDE ERPGDE ofet128 Efetor 128 3 MG183-6 protein a desconh acid Uncultured organism MAYRLGLDVGTASCGLIA WTLDEQGQPSELAYHSLD IWSEPLLPAKSSGVGEPR NAARRAARMLRRGIYRRA RRLRRIAHLASLLGLDRC AVPPDSGQDIHRLRALAA EQRVELADLLRIFLRMAKVNRGPELSGGGG KGKRGKKNPSETALADEA VATLVEADKKAAEEKKGI VGGVRELEKLMREAAQAL GKTELTLGQYLHYRRERG ESVILGKPDAKPCPLYPS RRMVENEFNRIWDTQAQF HPVMRDRTVRNQFFGAIF AQRPLKSPAPMVGRAPPRQLEQMAQTLA EKQIADLRWGMGKRAQPL Petition 870250090553, of 03 / 10 / 2025, p. 181 / 262 178 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence SPEQKAIVRELLNSQGEV AFSTIREALDKAGHPGPP GCGLNMERSSRESLKGNT TLAVFRKLGLDAEWNALD EKTQVQVINFLADLGSPD ALDSDDWHLNFETVQKRDPASTVATKFKFKFKV NHLRQRPKFGRLSSMGFD GGRMAYSIKALKKLTELM QEQGLDERAAAERAYADH FKAKPLSCELPLPPETGN TVVDVALRQVYRAVDRAM KALDGPPSQVIVELSRDM ALGIKKRSEIETKINVNN KARREAAQAIAEHGEQVT DKQMKIDRHYLLYCP YCDRRIELGEALGSETER EHILPRALTRVGGKRSQL VLAHRTCNQQKGNRTPWQ AFGNDEALWRIIETRAEQ LREKQFGKARLLLLKDW EEEVLDDKAIQDFTDRQF HEGSWIAKLTAQWLRTVC ADVAVSRGELTAHLRKRFRIWLPVLPVLPVLQLPWQ DREGKPISEEEFRHHKLW WEGHGKEAGGIETERKPN KRIDHRHHLVDALVISLT DRKLFQKMAENYKQEREK ERRGERAKLSLYEAPPIP SLRELAVEIVTNAKIRHK PDRYPDGPLFEQSAYGLN RKPNAEGKQQLAISKPLAKKKKALKKKALKKENK IESEVTRSTVLKAFDSRI AAGTSIKQVFDEAILHPQ FGTPIRRVRLLGDSEDTA TRVVHTNRHGTQLEKRYP HAGNAYLEIRVEGNKLVG APRLVKPLEAMREKGLRP PTGVRRFWKKDTISYNGA RYIIIGKIISKNGGTLCLV Petition 870250090553, dated 03 / 10 / 2025, pp. 182 / 262 179 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence PVTETCTHDELPHELKKS VSGKSLASVTIIDV Effector ores MG18 3 123 Effector MG183-7 protein uncultured Organism MAYRIGIDLGTASIGLQLVQSYDVVC IFQEPVEPAVAGGVGATK ASTRGSARRTRRLIDRRS RRLKNLAEICRLLDIEPK DISPDNGRSLHEARSKAV TEPIALTDLARIIFRISK RRGYSGGFKVKKEGDKGQ VQSGISHLKELMAKANCQ WLGQYLLHRFNKGETLKL KEAGLEYVREQDREQDWALQDREQD IPLKELFHKTLFYQRPLK SVTAMVGNCSLEPNLPRA PMCQ PAAQAFRIEKQIAD LRWGMGRRSQPLTTEQKS VIRNLLRSKDKATFLQIY TALEKADCPKPEHRALNF DRPSRPELIGNKTLKAMD KLGLADDWQQLDEGTQLNFLADMQILSPDRPNLPRA WHLQYKGKSGKQRKFPKP MVEFIKLMVDSEKFDRLS KLGFDGGRSAYSIKALKA LTGEMQNGLDEYEAIDKM YPANDEQPDLQTYLDLHK PSGNIVVDLALRQLRYAV NNAIDAMGCTPPAEIIVE LSRDMGLGLKKKKKKKKKKKKYE GHAATSTNIFRWRLWQEQ DTNCPYCERKMGLADAVN GNITNLEHVIPRSLTRVG RQQDHIMLAHRKCNDEKG DRTPWQAWGQDENKWKII TEHAKTLEKKRFTKAHL LTLQDWKHEIIDADIIKD FTNRQYHQTSWIAKLATQWSRRMICTASV HLRRIWGLNTVIPEIRYE Petition 870250090553, dated 03 / 10 / 2025, pp. 183 / 262 180 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence SGLPVFDTDKNIITKAF DQFKPYWEGHNNNHSGVQ RTDQIIEKRIDHRHHAVD ALIIALTTRSLYQKMALN YKKLAEKASSGKKVRLTL SVSPPLKNQHRISKHRISKHRDKHSLKHSL GTAYGATWVEDENHPNAD PRHLLTLRVKLTDLADKK SKPDTIRKKLIDIASPQT RKLVLDAFDAGIGAGKQP VEALASIQNPQYRTPIKK VKMLRGSVDTANKIVFES RNNSEENSLYKYLQNDGY AYLEVDKSGEKKTRPVT REQUIREMENTS FKGDTVEDTKDNQKFVIR QIKAQSDGLLMLVPITEA REVRDLSSSQGLRTVSGA SIARLKLVTNA Effect ores MG18 3 124 Effector MG183-8 protein a desconh ecido Uncultured organism MSYRLGIDLGTASVGLSC INILAYTCAHPT IFPEPVEPATAGGIGSTK ASGRGMARRTRRLIDRRV SRLRNIASVCELLAINPQ NIPADNGQSLHEARSQAT TQPISLEDLARIFFRMAK RRGYAGGFQVKKEGDEGQ VEGGISQLKQLMKEAKCD WLGQYLLHRFNNGKTLKL KEAKPNGLEMKVSAQLEQLEQLEQ HNDRPLKEIFHNAIFYQR PLKSVAAMVGQCPLEPNL PRAPMSQPAAQAFRIEKQ IADLRWGMGRRAQKLSSE QQSVIRELLATKDKATFL QIYKALEKAGHPKPEHRG LNFDRPSRPELKGNSTLK AMDKLGLAEQWQALDEGT QISVQINSPLEPNL RDDWPTRFRGKNGTPRKF Petition 870250090553, dated 03 / 10 / 2025, pp. 184 / 262 181 / 251 Cat. SEQ ID NO: Descrição Tipo Organismo Outras Information Sequência KPKVIDFINAMVASGKFE RLSKMGFDGGRSAYSIKA LKRLTEKMREGMDEYEAT AALYPPPVKQAERLTHLS PHKPTGNIVVDVALRQMR FAVYNAIDAMGGEPPKEV VIELSRDMGLGLKRRGEI EKGMDRNQRERKKAKEDL EKNGHSAISTNIFRWRLW QEQDTNCPYCERKISLGA AVDGHETNLEHIIPRTLT RVGRQQDHIMLSHRSCND EKGNRTPYQAWGHDANKW KIIEERAKALEKKRRFAK ARFLTLQDWKPEIINSDI IDDFTNRQYHETSWISKL AAQWMRTVCSDVAVSRGA MTAHLRRIWGLNTVIPEI RFEDGLPVFDTEKNLIDK TTFEQYKPYWEGHNNNHS GVQRTDQMIEKRIDHRHH VIDALVIALTSRSLYQKM AKNYKTLSERAQIDKHVK LKLSVNPPIKNVRAQALE MVRNYHIVHKPDRHVGGS LFKGTAYGVTWVENDKDP NADPKQQLTLRQNLVTLA DDKSKPDAVRKKLEKIAS LDTRRIVLNAFDKHIAAG KTAKEALNNIQHPQYRTV IRQVKMLRDSASTAWKIE FNSRHSTPDKPHYKYLQY DGYAYLELTETPGEKPEP RLVTQPEALQKKGQPIPP NNRRFFKGDTVEDTKDGK IFIVKSFREQGLQIFLIP ITEAREIADMDATKRLHK LSQKEQGRRVVGGASIAR LRILS Efet ores 125 Efetor MG183-9 protein is found in the Organism no MKYRLGLDVGTASVGLVA YELDGRGQPVDVLYHSVR IFKQAARREHRQQMRQHQ Petition 870250090553, on 10 / 03 / 2025, page. 185 / 262 182 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence MG18 3 cultivated RSARRLRKLAHLAPSLLG VAPEAVARRRKPHILEVR ARAATEKVALEDLLRIFL HLSKRRGYAGTFCVKKSG DTGKVQKGIGELQKDMNE AGCETLGEYLWRRHQQGQ PVRLKAYGLYAGREMIRS EFGQIWATQEKEHEQLGG AHEGRPLREIFEGAIFHQ RPIRIPRAGNCSLETSLP RSPQVQPAFQEFRIEKQI ADLRWAKKGRRHPKPLEE PAKQVIRKLLSEREKVKF EQIYEALEKQGIPVASGE YLNLSSGDREDLRGNGTN ACMKRLGLEQEWQNLSDR HRITALNLLADEGSPDIF DKKKNWHETIARGKQRAD RTPEYRCIPREVVKFVNS MIDTGEFDWISKMGFDSG RSAYSIKALRRLTAVMRE KNLDEADAKNLLYPQTAK TAKRGGLLRELPPHKHTG NVVVDVSLRQVRREVNAA IRKLGGPPDSMVIELFRD MPAGAKRREEIAERNKKN QKAKKRAAREIKEKTGNA ASEKAIARHLLWTEQDRK WCPYCTKEDISIFDALDG SKTELDHIFPKSITRIGK RRNYLVLAHRSCNQEKGA QTPREKWGDNPERWKVIQ ERAKQYGKKRRLGKKRQL LSKESGDALLDSKEIGDF SDRQFHDSSWISEICARW MKVICSYVEVSRGILTAS LRRKWGLDTVIPEVRLEE ELPILDRDDQLITREEFE RHRAFWEERGEEGDSSKT SRKIEKRIDHRHHLVDAM VLGLTSRSLYQKMARAYK REAEKAGASVNKRKIPLR Petition 870250090553, dated 03 / 10 / 2025, pp. 186 / 262 183 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence AEPPIRHIRELALDLVRN CNLTHRRDHWPGGPFFKE QPLAVVKIDKQDWFAQRK TLSEIAKKPQGANLESWI QTVRGRIGRIEPLSTRET VEKAFGERIEAGMNPNEA LAENFREGNEA RVRIRAREKADEAILVEH HGKFQNRPFEKYMKTDGY ICLELDMQQGGARLVTLH EAMKSGRLEAPKGVRFFK GDTVLNTSDKKRYVVRQI KAAKGGSLVLIRHTETRE AKHMDSASGKKSVSGKAL LELTLIPDVWPPHSSE EfetG 183 Efetor MG18310 protein a desconh ecido Organismo não cultivado MGYRLGIDLGTASVGLVC IKLDANKKPAGIAYHCAR IFQEPVESATGGGVGNTK ASARGTARRTRRLIDRRV NRLQDLAAICKLLNIDPQ TITPDDGRRLHEARSQAV TKPIALEAKDLGFRMKGVGKVGGQDEQGGKVGNTK VEGGINQLEQLMQAANCD WLGQYFLHRFNNGETLKL KEAKPIGLYVSRDMVEAE FEQIWKIQSAAHPLLNGQ HDGKPLKDVFHNVIFYQR PLKSVAAMVGQCPLEPGL PRAPMSQPAAQSFRIEKQ IADLRWGMPEQRAQQAQAQMLQACLKEFLKE QIYKALEKAGCPKPEHRG LNFDRPSRPELKGNSTFK TMDKLGLAEQWQALADGT QVSIINLLADLGSPQEVD REDWFTRFRGKNDTQRQF KPEVVNFINAMVASGKFD RLSKMGFDGGRSAYSIKA LKKLVGKMREGLDEALDEQLAQPYPLQH SHKPTGNIVVDIALRQMR Petition 870250090553, dated 03 / 10 / 2025, pp. 187 / 262 184 / 251 Cat. SEQ ID NO: Descrição Tipo Organismo Outras Informações Sequência YAINQAIDAMGGEPPTEV VIELSRDMGLGLKRRGEI EKSMDKNQREREKAKKDL EENGHPATSTNIFRWRLW QEQNTNCPYCERKIGLGA AVDGNETNLEHIIPRTLT RVGRQQDHIMLAHRACND EKGNKTPWQAWGDNADKW KIITERAKALEKKRRFAK ARFLTLQDWKAEIINSDI IDDFTNRQYHETSWISKL AAQWMRTVCPDVAVSRGA MTAHLRRIWGLNTVIPEI RIESGLPIFDTEKKVISK ADFEKYKPYWEGHNNNHS GMQRTDQIIEKRIDHRHH VIDALVIALTSRGLYQKM ARNYKVLSERAQAGERVK LTLSINPPLKNIRAQVLD MIRKHHIVHKPDRHVGGS LFKGTAYGVTWVENDKDP NTDPKQQLTLRENLDKLA DDKSKPDTVRKKLLKIVS PDTRRLVVDTFDKRIAAG KTVKEALSNIQHPQYRNV IRQVKMLRDSAGTAWKIE FSSRHSNPDKLHYKYLQY AGYAYLELTETPGEKPEP RLVTQPEALQKKGQPVPP NTRRFFKGDTVEDTKDGK RFIIKSFRDQGLQIFLMP ITEAREIADMDSTMKRHK LSQKQQGRRAGGGGSIAR LKLVN Efet ores MG18 3 127 Efetor MG18311 protein a desconh ecido Organismo não cultivado MSYRMGIDLGTASVGLVC VGLDTNSRPTNITFHCVR IFQEPVIPATGGGIGSTK ASTRGAARRTRRLIDRRI GRLQNLAQIFELLGIEPK SIPPDNGLLLHEARSQST SKPIKLEHLAKVFFRMAK RRGYAGGFQVKKAGDEGQ Petition 870250090553, on 10 / 03 / 2025, page. 188 / 262 185 / 251 Cat. SEQ ID NO: Descrição Tipo Organismo Outras Informações Sequência VEGGIYQLNQLMKGAKCE WLGQYLLHRFKNGETLKL KKAKPVGLYVSREMVEAE FEQIWKIQSAVHPVLNEQ RNGKTLKSIFHNVIFYQR PLKCVASMVGQCPLEPNQ PRSPMSQPAAQAFRIEKQ IADLRWGMGCRSQPLSRE QKTVIRKLLHTKDKATFL QIYKALEKAGCPKPEHRG LNFDRPSRPELKGNATLK AMGKIGLADQWQTLGNGA QISIINLLADLGSPQELD RGDWPSRFRGKNGTPRKF KHDVVEFINTMVASGKFD RLSKMGFDGGRSAYSIKA LNMLVERMREGMDEYGAI NFLYPQPDTKQDLLTHLS PHKPTGNIVVDVALRQMR HAVNQAVDAMGGDPPSEV IIELSRDMGLGLKRRGEI EKGINKNQRERNKAKEDL EKNGHPATSTNIFRWRLW QEQDTNCPYCEHKIGLGA AVSGNETNLEHILPRTLT RVGRQQDHIMLAHRHCND EKGNRTPWQAWGQDKDKW KIITERARALEKKRRFTK ARFLTLQDWNPEIINSDI IDNFTQRQYHETSWISKL AALWMRSISPDVAVSRGA MTAHLRRIWGLNTVIPEA RFESELPVFDTEKNLISE ETFERYKPYWEGHNNNHS GVQRTDQIIEKRIDHRHH VIDALVISLTSRSLYQKM ATNYKALSERSQTGERVK LKLSVSPPLKNIRTYALD MVRNYNITHRPDRYVGGS LFKDTAYGVTWVENDKDP NADPKRQLTLRMNLETFS NDKSKPDAVRKQLKKIVS Petition 870250090553, on 10 / 03 / 2025, page. 189 / 262 186 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence PDTRRRLIIDTFDQRIAAG KTAKEALMNIQHPQYRNI IQQVKMLRGSASTAWEIE FNSRNSTSEKPHYKFLQY DGYAYLELREVHRKKPEP HLVTQPEALKQQSQQPQQPQYRNI NTRRLFKGDTVEDTKDGK YFVVKSFREQGLLIFLIP VTEAREIADMDATMKRCK LSQKSQGRRTVSGPGIAR LKLVD Effect ores MG18 3 128 Effector MG18312 protein a desconh acid Uncultured organism MAYRLGIDLASVC LQLDGKNQPESLPYHCAH IFQEPVEPAKGGGVGATK ASTRGSARRTRRLVDRRA RRLRDLAEIFRLLQVEPE TISPDNGIKLHDARSQAA TEPIELPDLARIFFRMSK RRGYSGGFQVKKEGEEGQ VQGGINHLKELMTEAKCE WLGQFYLLGELLKLGTLKL KEAGLYADRGIVESEFDQ IWRTQAKAHNILNKLHNG IPLKQLFHKTLFYQRPLK SVTAMVGNCSLEPNLPRA PLCQPAAQGFRIEKQIAD LRWGMGRRSQPLSLDQRT VIRELLNQKDKATFLQIY TALDKAGYPKYPKPHRPSLDRPVRPNKTLKAMNG KLGLSEDWLQCSEGTQIS ILNFLADIGSPQEVDRPN WHLQYKGKNGKQRIFSEK MITFINQMVHSSKFDRLT KMGFDGGRSAYSIKALKA LSKEMREGLDEYDAIEKL YPQSDEKPDLQPHLAIHK PTGNIVVDVALQLARYAPQALIGIEGIGE LSRDMGLGLKRRGEIEKG IDKNRRERKKAKDDLEAN DHTATSTNIFRWRLWQEQ Petition 870250090553, of 03 / 10 / 2025, p. 190 / 262 187 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence DTNCPYCERKMGLGDAAN GNITNLEHIVPKSLTRVG RQQDHIMLAHRKCNDEKG DRTPWQAWGHDRDKWKII TERAKALEKKRRFAKARL LTVQDWKAEVINSDWINSDQIIQAWISKYQHETS WMQTVCADVSVSRGRMTA HLRRIWGLNTVIPEVRFE TGMPVFDNDKQLISKEDF DRYKPYWEGHNNNHSGVQ RTDQMIEKRIDHRHHVID ALVIALTTRSLYQKMALD YKKLAERVRSGENVRMSL AVRPALKNMRQQALEMIR YHRISKHFPLKFPLK DTAYGVTWVEDENDSNAY ARQQLTLRVRLAGLALTK GKLDKPETVRKKLMAIAS PETRKLVLGAFDANISAG KSPDKALADIQHPQYRTP IKKVKLLSYSVDTASRIE FTSRNHSTDNPLYKYLQN SGYSFLELTQPPPSPQPQPQQPQPQPQTKKKKVDANISAG KSPDKALADIQHPQYRTP ICKVKLLSYSVDTASRIE NAIRFFRGDTVEDTKNGQ RFIIKSFREQGLLVFLIP VTEAREIADMDS™KQHK LSQKQQGRRSVSGLGIAR LKLVD Effect ores MG18 3 129 Efetor MG18313 protein a desconh ecido Organismo não cultivado MKISYRDIALDAGLAGLAGLA GELDASGE LYIFSEPLLPPKAGGIGE PKKAARRNARLARVIDR RARRLKRIALLSRLLGID HSNVTPDDGQHIHALRAK AATEPLEIEDLLRVLLKL AKRRGYKGSFKVRKEKDE GVVEPGINQLRQHIADAG CNTLGQYLSKRFDAGDTL KLKEAGLEFYAHRAHRAKHLEHPLEH Petition 870250090553, dated 03 / 10 / 2025, pp. 191 / 262 188 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence PDPLDEHKRLRSIRDQFH GAIFYQRPLKSVAPMVGN CALEPSLPRAPMAQPAMQ AFRIEKQLADLRWGMRRN APGLTAEQKTLIRKLLND PGKLTKEGKLSFKKIYEA LEAEGLRPDYPRSLNMER SSREDLTGNRTLRVFKDI VLLDEWRALDEITQLRVI NFLADLGSPEQVDQLDWH DRYTKTARVKNPKSGKWE EKHVRRDLDHKLVEFINR MVDTKKFDRLNKMGFETG RASYSIRALEKLAAAMRE ENCDEHEAIQHLYPPPEA TGELLPQLLPHPPTGNVV VDVALRQVRRAVNDALTR LGQPPAEIVIELSRDMAL GLKARGDIERKIDKNKRQ RQDAKKALESNEPPIPGT DRNVLRYILWQQQDTHCP YCGERISFGQAVDGNATH FEHILPRSSLTRVGKQRNH LVLAHQSCNNAKGDRTPF EAFGHDGERWKAVEYCAS VLKSNKQFAKARLLALTD YEHEILDDESIADFSERQ FVETSWIGKLTAQWMKEV CTKVSVSRGLLTAHLRRI WKLETVIAEARLNAEPPL PVLDADGNKITLDDFKRF KPFWEGHNGKDHPRTDRK IDKRIDHRHHLIDALVIA QTSRSLYQRMAKHYKELA ERRREGEAVRMTFSVEPP LRDVRSQALVLVREAAIR HKPDQFSSGMFFQKTAYR KAYSDDGDSRLSVRIKLE ELTDNKGSIDKARKGISD IVSSHTRRVVSNEFERRI QAGESVKQALSLAIIDPQ FNTPIKKVAVFQRVGRGF Petition 870250090553, dated 03 / 10 / 2025, pp. 192 / 262 189 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence VDGSSAFPVKNSWYLSDG YAYVSITEEDGRIVAAES VPLISAAAQHASRTAGER RFFRGDTLRDKATGTMYI VHQILANATVRVAPVTES RSWIELGADAGATQFGRA EQFLIGAR 138 ores Effector MG18314 protein a disconh acid Uncultured organism MRYRLALDLGTASVGLVA YELNETNAPLGVAYHVVR VFDEPVLPAKGGSVGEPK KAARRQARQRRQLERRA RRLRGLAQVLGEALGLDL RSVPPDPGQHIHALRSAS NAHVELPGNLLVLLLA KRRGYAGGFRAVADDNDD SQVKAGIDRLRTEMAERG CDTLGDYLSWRAANGQTL KLKTVGLYADRDMVREEF ERIWRIQATHHPRIAAGG EALRKRVAERIFHQRPLR SPAPAVGNCPLEPSLRRA PMAQ PAAQAFRIEKQIAD LRNGRNGRWWTRAQDLQPLQPLQTVRTQTVR RALQKRGCPRPEIGWLNL DRSSREELIGNKTDAAMA RLGLAEDWAGLEAGQRVT VINLLADIGSPETLCIPG WHEQLVTGGKQRRKRVLP AAVVAFIDKLAAQPAFGR LGAMGLDGGRSAYCVKTL CRLADAMGEKGIDEHEAVEAVQAQYEAQ GRPRPTGNTVVDVALRQV RYTVNAAIRHLGTPPTQI IVELSRDMALGINRRREI EYRINKNQRARRQAAEAI AAHDGRVTHSAIRRYLLW REQDEQWCPYCERPINLS DALDGNATHYEHIYPKSL TRIGKQRDFLVLAHRDCN DFKGGNRDDARTPDRTP Petition 870250090553, dated 03 / 10 / 2025, pp. 193 / 262 190 / 251 Cat. SEQ ID NO: Descrição Tipo Organismo Outras Informações Sequência WQIIKQRAARFREKRLNG KAKQLLAQEPVDRALNDK VINDFSARQFHESSWIAK QAARWLREVCGDVAVSRG MLTAHLRRSWALETVIPE ARLAEGLRLRRDDGKLVS AAEFQRYRRYWNGDRSGE ATERELDKRIDHRHHLID ALVIGLCDRSLYQRMARD YKQAQERGETRLTLRVKP PLPNLRAVAVELVRHCNL SRKADRYVSGRLFQDTAY GCTPDGQHLTKRKAVAEL GGGAKATLSKVRKDIDKI VHESTRDLVRQAFERRVA AGRSPEAISEPIQHPAY GTVIKRVLLLDEKTEGTK AVDHYARGDHLFKHLKPF DNAYLELVAGSGSKFEKR LIRRYEAKNHTMPVGVVG FAKGDTVRHPDNGLHYVV GQIKTERGGVLLLARLVE TDPVDKVKGSPGFAYMSS GPALAKLEIVPDVIAPDS SD Efet ores MG18 3 131 Efetor MG18315 protects a device from the organization and does not cultivate VAYRLALDVGTASLGLVA LTLNDQQEPVDVAHSAVH IFSEPLLPAKSGGVGEPK KAARRLARQRRRLTERRA RRLRRIAHLSPLIGLQAS QVEPDDGQHIHALRAKAI NQRIELPELLNVLLKLAK RRGYAGGFKVKKDGEDAG QVQSGIENLKTRLSDNSC STLGELLHKRFGDTEHAG RGPRESLKLKTLGLYAHR EMLEDEFERIWSEQARHH PILKTEAAAYSVRGVAEK LPIKQHFKEAIFYQRPLK SVAGMVGQCVLEPTLPRA PAAQPAAQAFRIEKQLAD LRWGMGRAQRALSKEQRD Petition 870250090553, on 10 / 03 / 2025, page. 194 / 262 191 / 251 Cat. SEQ ID NO: Descrição Tipo Organismo Outras Informações Sequência HIRAMLLDPEQLNRDGAL TFGKIYKSLEKAGLRQDF PTQFNTDRFSRETLLGDR TTKAMSEAKMLGRWMALD TITQLRVINFLANLGSPE SVDSPNWQERMEPAPKPE VVAFVNQWVDSGTFDRLG KMGFDTGRAAYSIKALKQ LAGKMQKGEGCDEHAARD ILYKPSAPTGELLMHLSQ PAPAGNVVVDVALRVVRH AVNQCLQAMGQPPAQVIV ELSRDMALGLKARGEKEK GIDKQRRARLYAKSQIEG SQPGRTATNNDIFRYLLA QEQDFHCPYCTRRLLELGE ALDGNATNADHILPRSLT RVKRERSHLVIAHRACNA AKGDSVPLEAFKGDADRI SAIENCANILKRKRSFRK ASYLLSESYDAEKLDDKS LEDFTARQFAETSWIAKL VAQWMTDVCQDVSVSRGE LTAQLRRAWKLDTVIPQV RLETKVDPTSDHPDNHLP LLDDNKPAKPVSREDFDR FRACWENHHSPEVERTDR RIDKRIDHRHHLIDALVI GLTDRRLYMNMARGYKER MEQRAAGVRGIKPWQTPE PPLRNIREIALRLVREVN VKHKAHRYPAGAFFQQMA YAKTYTDDGKSRIALSID LIALTDSNHSLDKARKGI SDIVSPGTKEIVSNEFER RISAGQSVKTALSTPIAD PRYGTLICQVRVYQRLGR GYASGEDAIKVDLVGRPY RASTPAEKHYLSDGYAFI ALIANEADLVIDAVSVRS ADAPNFDLSRVARRIFRS DTLVDESGNRHLVHQILA Petition 870250090553, on 10 / 03 / 2025, page. 195 / 262 192 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence DGVIRTAPLTESRSWIQL GAEAGAKQFGKAAVMQLK IER Effect hours MG18 3 132 Effector MG18316 protein uncultured Organism não cultured MAYGLINKGLIQDLINK LIGHTS LIGHT IFQEPVEPAVAGGVGATK ASTRGSARRTRRLIDRRS RRLKILAEICRLLDIEPE DIPPDNGRSLHEARSKSV TEPVDLADLARIFFRMSK RRGYSGGFKVKKEEDEGQ VEGGINHLKKLMAEANCQ WLGQYLLHRFNKGETLKL KEAGLYADRQ IVLDQEQLDWHLDWHDPHEARSKSV IPLKQLFYNTLFYQRPLK SVTAMVGNCSLEPNLPRA PMCQPAAQAFRVEKQIAD LRWGMGRRSQPLSAEQKS VIRDMLSSKDKATFLQIY KALDKAGCPKPEHRALNF DRPSRPELAGNKTLKAMD KLGLADEWRQLDEKTQILNFLAGQILQDSNG WHLQYKGKSGKQRKFSER MVEFINRMVDSGKFDRLS KLGFDSGRSAYSIKALKA LNKEMHSGLDEYEAIDKL YPVNDEKPDVQAYLELHK PTGNLVVDVALRQLRYAV NNAIDAMGCIPPSEIIVE LSRDMGLGLKRRGEKKKKKKKKKKKKKKKL HHAATSTNIFRWRLWQEQ DTNCPYCERKMGLGDAVN GNITNLEHIIPRSLTRVG RQQDHIMLAHRKCNDEKG DRTPWQAWGHDADKWKII TERAKSLEKKRFTKARL LTLQDWKAEVINNDIIDD FTNRQYHQTSWIAKLATQWSRMRICV GRRMTASVG Petition 870250090553, of 03 / 10 / 2025, p. 196 / 262 193 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence HLRRIWGLNTVIPEIRYD SGLPVFDTEKKIIPEEEF VRFKPYWEGHNNNHSGVQ RTDQIIEKRIDHRHHAVD ALVIAMTTRSLYQKMALN YKQLAEQVSNGLQTLKPLQQQQNVVRDMVRSV HHRITHKPDRYISGSLFK GTAYGATWVEDENNPNAD PRHLLTLRVKLTDLADKK SKPDTVRKKLMDIASPDT RKLVLDAYDAGISAGKQP SETLANIQHPQYRTPMKK VKMLRDSVDTAEKVEFNS RNNSAENPLYKYLQNDGYGASVIELKSLIT MQEGQRSKHAHKSSKTIR FYKNDTVIDTEDNKIYIV KQIKAQSGGSLFMVPVTE AHEISQMENISKDSGIPP KQQGRHIVSGPKIARLKL SP Efet ores MG18 3 133 Efetor MG18317 protein a desconh ecido Organismo cultiva nãoGTDIALCGLYLYL VNLDTDKQPTSIAFHSLH IFPEPLLPAQSGGIGEPK KAARRKARMARRIIDRRS RRLKRIAMLASLINLDHR NIPADDGQHIHSLRADAA TKRIDLDNLIRIFLRLAK RRGYAGGFKKKEGEEGQ VQTGINALESKMREVDCK TLGQYLYHRFKAGLIKEFLIGELDMHR IWDTQSTYHSILNEIRPD PLIANHPARAIRDQFFDA IFHQRPLKSVA™VGNCS LEPSLPRAPRAQPAAQRH RIEKQLADLRWGTGRKAE SLTIEQKSAIRELLLDPN KLTKEGKLSFEKIYKELD SKNLRPVSINKLNMERSS REELTGDLGDMDLGDM Petition 870250090553, on 10 / 03 / 2025, page. 197 / 262 194 / 251 Cat. SEQ ID NO: Descrição Tipo Organismo Outras Informações Sequência LEIWQTLDDLTQLRIINF LADLGSPEQVDQPNWHTR FTKTKHVKNEATGRWESK TEFRAIDPQVVSFINKLV ESGQFNRLGNMGFEFGRT SYSIRALEKLALVMKETG CDEHTAMQKLYPKEAPTG ELLTQLPPHKPTGNVVVD VALRIVRRAVNEALQKLG EPPDQVVIELSRDMALGV TARSKIENQISKNQSYKK RIAKALSENDPPIQATEI RTLRYMLWDQQNQRNCPY CSRPINMYQALDGGETNF EHILPRSITQVGKQRNHL VLAHRSCNDEKGDRTPYE AFHHDIERWKAVEECAAI FHKKKLFAKERLLLLPDY EHETLDDTTLADFSDRQF IETSWIGKLAAQWLRLTC SDVSVSRGILTAHLRRIW KLETVIPQARFDAGLPVL DQDGEEITINDFSHFKAY WEGHNGKEHQRTDRKIDK RIDHRHHLIDALTIAMTS RSLYMRMANHYKELAERR AHGEAVRMKLFVEPPMPA IREKATEIVTTPNIQHKP DRLGGGAFFQEFAYGTVQ VEDKDELQLCRRKQLSTL IKPNDKPDKARKILGDIV SQEVRKLIMDAFEARIQS GMTPFQALQDPIDYPAYK TKLKRANFLYGSAESTST IHHPHKKPKYIKRLIDNG WACLQVNSTGKEVETKLI SPRMFAKVGADGADGITT YFKGDTVLNSKTQKIYVI KQILAQSGGLLVLMPVVD ARKVEGMTASEGLKKISG GGLRNLIRL Petition 870250090553, on 10 / 03 / 2025, page. 198 / 262 195 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence Effect hours MG18 3 134 Effector MG18318 uncultured protein Uncultured organism MAYRLALDLGTSSIGLVA IRLDGDRQPAEIIHHACR IFAEPLDPSKKARGRRKARGRRKRLKDRKDRKDRG RRLRRIAALAELIGLAPS TVEADEGQSLHQLRSEAV TRAIPLPDLLRVLLRMAK RRGYSGGFKTKREDQEEG KVEGGISRLKEEMAKAKC DYLGQYLYHRFQNGETLK LKEAGLYADREMVEAEFD HIWAIQSQHHAALNDNHN GETIFKLQLQLQLQLQLRMAK KSVAGMVGNCALEPSLPR APMSQSAAQAFRIEKQLS DLRWGGGRRAELTAAQRD VIRGLLGEKKEVSFTAVY KALEKAGCSDDRGRTLNF DRTSRPALRGDSTFATFD KLGFLDAWLALPAGVQVS TLNFLADLGSPQEVDRPD WQNQYRRKEFLDGARPAGCVDRVDRWGTF KMGFDGGRAAYSIKALNK LTEWLRAPWWPGDWKGDK TVSEDNAIRICYPDSARR NKSSQRKLEPHAPTGNIV VDVALRQLWYQANACIEK LGEPPTEVIVELTRDMGL GVKRRNEIEDRINKNRRD RQHAADELSRHGELVTDR NIFRQLEQLEQLEYCPYCPYC ETRIGLHEAVNGGETNVE HIVPRSLTRVGRQRDHLV LAHRRCNDEKGDRTPWQA WGKDPDRWVQIEAHAKAL EKKKLFTKARLLTIKDYE SEVMDDAAIEGFSERQFH ESSWIAKLAAQWLCAVCP SVAVSRGELTAFLRRTWR LDPTVIPEFRENVLDRFREQLDWRCWLPWRCW Petition 870250090553, dated 03 / 10 / 2025, pp. 199 / 262 196 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence EGHDHDPGAEQTDRKINK RIDHRHHVIDALVIAMTS RGLYQKMARHWKAERDAG RKPNLSVSPPMRNLREQA LELIRKCNLTHKPDHYPA GKFFQETAYRRVGMDVNKVRTNGTLVRTSLV LDKARKAIGDIVSEEVRE IIVEEFEKRVARGMSPQE ALASPIPYPRYQNRKSSH NVTIKKVRVYQRMGRGYA DGEGVVPIIHVQRDGMEL HKYYLSDGYAYVSLKFDN GKIVSAESVPLHIAPRRS VLPVHSETRYTNDTFLDVARVARGYRSQIRSQIRS ALSLASEAREVRDMDADG GLMLVSGNGLLRLAPV Efect ores MG18 3 135 Effector MG18319 protein a desconh acid Uncultured organism MAYRLGLDLGTSSIGLVA VRLDEGRLPTEIIYHTCR IFAEPLDPSKGGVGEPK KARRKARLARGRLPARLKRLKRL IVDADDGQLLHRLRSEAV TRAIPLPDLLRVLLRMAK RRGYSGGFKTKRENQEEG QVEGGISKLKEEMAKVNC QYLGQYLYHRFQNGQTLK LKEAKPVKLYADRQMVET EFDRIWDVQSQAHAVLNG SHDGESLRKIFREAIFHQQSQAGMKVNCLEG LPRAPMAQPAAQQFRIEK QISDLRWGSGRRAQILTI EQRNVIRDLLNESKVSF VAIKKALDKAGCNDPQGR SLNTDRFSRPELRGDSTH AAFNDLGLLAEWQAPPPG IQVSIINFLADLGSPQEV DRPDWHKQYRRKDGVANPRE FKPEMVDFKFKFKFK DRLSKMGFDGGRAAYSVK Petition 870250090553, dated 03 / 10 / 2025, pp. 200 / 262 197 / 251 Cat. SEQ ID NO: Descrição Tipo Organismo Outras Informações Sequência ALNKLTDWLRNPWWPEGW KGDMSMSEDNAVRVCYPK AEHRECGLRKTLVPHPST GNVVVDVALRQLWYQVNT CIERLGEPPAEVIVELTR DMGLGIKRRNEIEDRINK NRRGRQHAADELAKHGEL VTDRNIFRYLLWQQQETA CPYCETRIGLHEAVSGGA TNIEHIVPRSLTRVGRQR DHLILAHRACNDEKGDRT PWQAWGSNTERWAIIEAH AKSLEKKKFYAKARLLTM KDYEGEVLDDAAIEGFSE RQFHETSWIAKLAAQWLR TVCPNIAVSRGELTAFLR RIWRLDTVIPEVRYEVSL PVLDTDKQPVTREEFNRF RRCWEGHDRDPGAEQTDR KIDKRIDHRHHVIDALVI AMTSRGLYQKMARHWKAE REAGRKPNLSVPPLMRDM REQALELVRNCNLTHKID HYPAGKFFQETAYRRVLM DDDKKRLVIRTTLASLAD NKTPLDKVRKAIGDIVSD EVRSIVSDEFEKRIARGM GPQEALSSPIAYPRYRNR KNGREVMINKVRLYQRMG RGYADGEDAVPIIHIQRQ GKELLKHYLSDGYAYVSL KFDNGKLISAESVPLHVA PRRSVRPEPGETRYYTND TFQDTSTKRRYVVRQIRA NAALALTLVSEAREVREL DANAGLMLVSGNSLLRLA PV Efet ores MG18 3 136 Efetor MG18320 protein a desconh ecido Organismo não cultivado MKYRLALDIGTASCGLVG VKLDENYEPTEIVHHSLH IFSEPVLPHAVGETGEPK KASRRKARLARRNIDRRA RRLRRVAMLASLLDLDHK Petition 870250090553, on 10 / 03 / 2025, page. 201 / 262 198 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence TIPADKGQRIHEIRAQAP QKQIELDDLVRVFLKLAK RRGYAGGFRTKTDKQKDE DSGIVQPGIEKLQIVMKA VDCKTVGQYLQHRFRNGE TLKLKEVGLYTHRDSLVH EFDCIWNEQAKHHPILNE TKPDPVHGGERAIRQQFF DAIFYQRPLKSVAPMVGN CALEKNLPRAPMAQPAMQ AFRIEKQLADLRWGMGRS AQTLTSEQKSLIRNLLND PDQITKEGKLTFKKVYAA LEKKGLMPTTRRSLNMER SSREELYGNRTLRAMRDL DAIEQWLTFDPVTQIRII NFLADLGSPEQVDLPDWH DRFTKRKRAKNPKTGRWE EKQEKRDLDTNLVSFVNK LVENGKFGRLGDMGFESG RASYSIRALEKLTRKMHE TNCDEHTAIQSCYPPPPP TGELLMHLPLHPPTGNVV VDVALGAVRRAVNNALTK LGEPPTEVIIELSRDMAL GLKARGEIEKKIDKNRKL RENAKKALEANDPPILGT DNNVLRYILWQQQDNHCP YCSDRISLGEAVSGNATN FEHILPRSSLTRVGKQRNH LVLAHRRCNDAKGDRTPY EAFSHDEERWNAIKYCAD VLEKKKQFQKSKLLILNE YERETLDDAAIEEFSERQ LHETSWIGKLAALWLQKI CPTPVAPSRGTLTAHLRR IWKLETVIAQARIEAGLP VLDQDGEKISPEEFERFR PYWEGHSGKGIERTDRKI DKRIDHRHHLIDALVIAQ TSRSLYQRMAKNYKALAE RQQAGETVRLLRLFVEPPI Petition 870250090553, dated 03 / 10 / 2025, pages 202 / 262 199 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence KNVREQALALMQSADIRH KPDRQISGNFFQQTSYRK TYTEDGKSRAVIRVPLTQ LTDTKGSLEKAKKGISDI VSDRTRKIVSGAFEQRIS SGKSVKEALAEPIKFRIQQQYFQRIGRIGR DGSSTFPIEHGRGFIKHY ISDGYAFVSIIENDGRIE SADSVPVFRAHRVNAAPK DGERRFFRGDTLLAPTNG KKYVIHQLLANATVRAAE VTESRSWIALGAESGATQ FGATALIKMTRL Efet ores MG18 3 137 Efetor MG18321 Organic ecosystems MNYRLALDIGTASCGLIA LKLDENREPVEVIHHELH IFSEPVLPHAAGETGEPK KASRRKARLARRNIDRRA RRLRRIAMLAGLLDHK KISADNGQRIHEIRANAS KKRIELDDLLLRVFLKLAK RRGYAGGFRTKADKQKDD DSGIVQPGIEKLQELCQELCKTVGFSYF TLKLKEAGLYTHRDMLVG EFEAIWAEQEKYHPILRA SRLDPVAKFADGKKNRP LREQFREAIFYQRPLCSV APMVGNCALEKSLPRAPM AQPAMQDFRIEKQLADLR WGMGRSALPLTSEQKSAI REMLNDPDQVTKEGKLTK KVKKYMPRATE SLNMERSSREELYGNRTL RTMRDLDAIGQWLTFDAT TQIRIINFLADLGSPEQV DLPDWQDRFTKRKRVKNP RTGHWEEKHEKRDLDKNL INFVNKLVENGKFGRLGD MGFESGRASYSIRALEKL TNKMRDANCDEHAIQPPHPPTMHPPLLLL Petition 870250090553, dated 03 / 10 / 2025, pp. 203 / 262 200 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence PTGNVVVDVALGVVRRAV NNALAKLGEPPAEIIIEL SRDMALGLKARGEIEKRI DKNRKLRENAKKILAEND PPITGTDTKIRRYILWQE QDTHCPYCSD DNFLTTRISLGSLGETRVH GKQRNHLVLAHRRCNDAK GDRTPYEAFGHEEERWNA VKYCADVLEKKQFSSKSK LLILNEYDRETLDDAAID EFSDRQLHETSWIGKLTA SWLQKICPAPVAPSRGML TARLRRIWKLETVIAQAR LEAGLPVLDQDGKKITPE EFDQFRPWEGGGKGIKGI RTDRKIDKRIDHRHHLID ALVIAQTSRSLYQRMARN YKSLAERQKAGEVVRLL FVEPPLKNVREQAFALVQ SVEIRHKPDRQISGNFFQ QTAYKKILTEDGKSRAVI RIPLLQLTDAKGSLEKAR KGISDIVSDHTRKVSSDAKSSKSVKSVKSVKSVQ IYDPQFKTLIKRVAVYQR IGRGFLDGSNTFPIEHGQ GFLKHYVSDGYAFISIIV RDGRIESADSVPVFRAHR TNGALKHGERRFFRGDTL LAFSNGKKYVIHQLLANA TVRVAEVTESRSWIALGS ESGAAQFGATALIKMKHL Efet ores M138 33 Efetor MG18322 protein a desconh ecido Organismo não cultivado MGYRLGIDLGTASVGLVC VTLTAEKQPASIAYHCAH IFQEPVEPATGGGVGSTK ASTRGNARRTRRLIDRRV GRLQDLAAICKLLGINPQ TITPDDGRCLHEARSQAV TKPIALADLARVFFKGRFKGQGQGQGQGGGGVGSTK ASTRGNARRTRRLIDRRV GRLQDLAAICKLLGINPQ VEGGINQLKQLMEAANCD Petition 870250090553, of 03 / 10 / 2025, p. 204 / 262 201 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence WLGQYLLHRFNNGETLKL KEAKPDGLYASREMVEAE FEQIWKIQSAAHSILNEQ HNGKPLKDIFHNVIFYQR PLKSVAAMVGHCPLEPNL PRAPMSQPVAQLRQRAQLRQLRQLRAGGR QKTVIREMLCMKEKASFL QIYKALEKADCPKPEHRG LNVDRPSRPELKGNSTLK AIDKMGLAEQWHMLDAGT QVSIINLLADLGSPQEVD RDDWPDRFRGKNGTPRTF KPEVVDFINAMVASGRFD RLSKMGFDGGRSAYSVKA LKKLDEXLAQMKPEQPEKGPEQPEHRG IHKPTGNIVVDVALRQMR YAVNNAIDAMGGEPPSEV VIELSRDMGLGLKRRGDI EKGMDKNRRERKKAKEDL EKNGHSATSTNIFRWRLW QEQDTNCPYCERKISLGA AVDGNETNLEHIIPRTLT RVGRQQDHIMLSHRSCND RTPWQWNPDWKW KIITERAXLEKRRFAK ARFLTLQDWKAEIINSDI IEDFTNRQYHETSWISKL AAQWMRTVCPDVAVSRGA MTAHLRRIWGLNTVIPEI RFESGLPVFDTEEKKNLI TKEQFEKYKPYWEGHNNN HSGVQRTDQTIEKRIDHR HHVIDALVIALTSKERQMYQMY VKLKLSINPPLKNIRIQA LDMIREHHIVHKPDRHVG GSLFKGTAYGVTWVENDK DPNADPKQQLTLRTNLEA LADEKSKPDAVRKKLEKI ASPDTRRLVLDTFDKRIA Petition 870250090553, dated 03 / 10 / 2025, pp. 205 / 262 202 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence AGKTAKEALSNIQHPQYR NVIRRVKILRDSAGTAWK IEFNSRHSSPDKPHYKYL QYDGYAYLELTETPGEKP EPCLVMQPEALKQKGQPV PPNTRRFFKGDTFEDTFKFKFQLIVKFQLIVK IPITEAREIADMDATMRQ HKLSQKQQGRRAVGGASI ARLKLVN Efet ores MG21 139 Efetor MG21163 protein a desconh ecido Organismo não cultivado MCLHPRYVLALDIGITSI GYAILLNDASGNPIRIIK LGVRIFDAAELPQRRGARSARRGARSARRQ HRKERIRLLIERSNLMPI ADMERLFSQGFERSVYE LRIDALDRLLSKEEAVRL LIHFSQKRGYKSNSKSEE SKDGSDSGKVLNAIAENK QLCAAKGYRTVGEMLLKD EKFMRINADGSVHTVHN EPDAYKVTFFARQMILDEI SSSQSQSQSQESFRSW FEKEYIEIWGSQRNFDEG PGGDSPYGGNQIEDKIGF CAFEAEEKRAVKASYTAE YFRALQTVNHLKLVDQNF KSAPLTEDQRKVVLDAIL KQSSLDYQAIRKKLKLPD STTFNMLTYGKKSQADVE KKKKLKHLLKLKLK KTDKNAVDRLSPDLRDRI AEIITLYSSDEKRREYLL AAGVPDEYLNPILTLSAK GTVHLSLKAMKKLIPHLE RGLIYSDACKEVYGEQTE QSSTQRSNRLSVTMDEI RNPVVLRAVSQATKVINA VVRTYGAPEVIRIELARE MGHTKDERNQDQDQI ATQNERIRDEIRRVKHDE PTGLDIVCYCLEQNGV Petition 870250090553, of 03 / 10 / 2025, p. 206 / 262 203 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence CLYSGKSIAYERLFENGY VEVDHIIPYSISFDDSYN NKTLVMTAENRQKGNRTP LEYMKGDPAKEDRFRTLV QTQVRSYKKRRNLLTESA ALHEDEKFKTRNQLVIQLVISLDLQL SSYRRRVQPVNGAITAYV RGRLGLQKIRGNGDLHHA LDAAVIGCISPGMVQKIT EYSKHQEMARRPGGYLDY ETGELLTKEEYDARFASG FPEPWPMFRKELEARLSE NPRKEIDLIGIPSYDSDE EIPPVFVSRMPKHKATGQ AHEATSKTISKTV KFLKELKLNGEGEIEGYY RPNDDLLLYRALVQRLQA FGGNAKEAFAEPFYKPKKH DGTQGPLVKKVKVYETAS LTVPINHGVAANGDMVRV DLYYVPGEGYYGVPIYVA DMVKSELPRRAVVAYKPY DEWKPMQPSNFLIIFLIFYNRYDSLYD GTGEKQIMRKEGLFYFKG LNISVGSIIIETHDRSYE KQGLGIKTLPLIEKYEVD VLGNYHKITQKGKQEEVR Efet ores MG21 140 Efetor MG21164 protein a desconh ecido Organismo não cultivado MEYTLGLDVIGLDVIGDLDAGQDLGGVRYGVR IFEAAEQPKTGASLAAPR REARSARRRLRRRRHRKE RIRALLVQEGLISQDCLD TLFVNSGFAKDVYTLRAE GLDRLLDEEEWVRVLLHL TQRRGYHSNSTAQAKSDK ETGVLKKALGKNIELMAK KGYRTVGEMPATDKFRV VGQDRNNKTRNKTRGVANFQVERFAQVNEW AQRSFGNPHAVEALEGRY Petition 870250090553, dated 03 / 10 / 2025, pages 207 / 262 204 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence AEILFAQRHFDQGPGGDS PHRKGDMRGMCTFEPEER RAFKACYTFEYFKLLQDL NHIRLISAKGDSLPLSKE QRQTLIALCHKSPDLKYT RLRTALNLPESVTFNRIR YQQQQGESIQEMEERLEK KEKFTQLQSYHEIRKALN HADKALLPALLQEPDHTT LDEMATILSLYKEDEARR SRLEALGLSQPVIDALLP LSFSKAGNLSLTAMRKLI PQLEKGVTYDKACSAVYG DHRAHSGAQRYHTLTLNQ TLRDSGALDNLTNPVVFR AISQTTKVLNAIIRKYGS PQTIAIELAREMRNNFQQ RKKIQNSYEAHQKVNEKA MKQVAELKGSRPTGQDLV KYKLYEEQQGFCLYSGTQ LEANRLFEPGYVDVDHII PYSICFDDSYNNKVLVLT SENRQKGNHLPMEYLASD AKKRERFIAWAKCCIRNH RKLQRLLKETLTEEDCRG FKERNLKDTQYITTAVYN LLNDYLEFSPNAPKQPVR AVNGSITAHVRRRLGLEK HRENGDLHHAMDAAVVAV TTPGMIQRISNYAKRREM GRKVKGKYVDLDTGELMT QEAFDAKYAPHFPAPWPH FQQELLARLSPDPDTEIR ALNFPHYDPQEVIAPVFV SQMPRRKATGPAHEDTIR SGKAPGYTISKTPLNELK LEEKTGEIENYYNPGDDR LLYEALKERLRQFGGIGK NAFEAPFHKPRKDGTPGP VVRSVKTIKKSNIGVSVN GGIAGNGSMVRIDVYRVP NDGYYYIPVYITDTVRGV Petition 870250090553, dated 03 / 10 / 2025, pp. 208 / 262 205 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence LPQKACVPDKPPEQWKVM DDSHFLFSLYPGDLIRVE RRTPIKLKPPKKAAEKSG ISRNECLVYFVSADISTA SICITTHDRKYIQKGLGV KRLSALEKYLPKHVQVQVQVKGLGV KRLSALEKYLPKHVGVQVGVRes MG21 141 Effector MG21165 protein a desconh acid Uncultivated organism MKDIFYTLGLDIGIASVG WAVLENDRSGDPKKIIAL GSHIFDKAEHPKDGSSLA APRREARGARRVTRRRRH RKERIKKLITDSGLMSLE DMQKLLTISS REVEVRYEVCLNEVCL IHFAQRRGYKSNSKAEEA KDAKESGAVKTAISANRR RMQENGYRTVGEMYLRDE QFRRVEPDGSIVMTVHND PDQYRVTVERSMLMDELA LIFAQQREQGNKWASEDF EEKYTEIWASQRSFDEGP GGDSPYGGNQIERMLGYAPKAYCAYTFEVSATFE FRLLQWVNSYCLVKVGEV SEPLTKEQREAVISLAFK SSGMTYTMIRKKLELAED VYFNMLSYGNKSVEEVEK TKPGHMQFWHKLRTTLKL TAPGTELSVEQLDDIAYI LCTCKSDDNRIRGLSEKG IPEEYVPQILELSAAKK PHLSILEGLEGL TYDKACEQVYGRLDGKPS GTERVSKLNIKMAGELNN PVVTRAVSRSIKVINAIV REYGSPETVRVELARELG KDFTSRARIKKRQDENAR ENEKAKEQIREYKKGDTV TGQDIIKFRLFEEQQGIC LYSGASLDASRLFEAGYV DVDVDSSIPYTYTYS KVLVLASENRQKRNCTPY Petition 870250090553, dated 03 / 10 / 2025, pp. 209 / 262 206 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence EYFGADEVRWERFVTLVN TKIRNQRKRQNLLSKAVS DESRKELRNLNDTQYL SRLVYNLINDNLLFSDRG NYKKKTQTVNGTVTAYFR KRLGLEKIRANGVIDVKVGVGVGVSP HSQRMERYRNGDAYIDYE MGEIISREDFDLRYAPKF PEPWPRFRDELEARLSAD PAKEIDIRKLHMYEGEEL PKPVFVSRMPNHKVTGAA HQETIRAAAKDGTVSKVN LSVLELDTDGEIKGYRP QDDMLLYNALKERLKAFG GFRKGADAGAGFPPKHFPKH NGELGPVVKKVKKYDVST LNVRTDRGVASNGKMIRV DVFKVEGDGYYFVPIYVA DTVKDKLPSRAVVAHMPY EKWKEMNEDDFVFSIYAG DLLHIRNNKKEIELELVDG AVGECIHKGKDLFLYYNS FGIASGKSIKKVLQLQDKVLQDKV VLGNVRIITAPEKRMGFK Efet ores MG21 142 Efector MG21166 protein a desconh acid Organismo não cultivado MKYTLGLDIGIGSIGWAV LQNGADGTPVKITDLGVR VFPKAEDSDTGASLALPR RNARSSRRRIRRHRKE RIKYLILIDEQHLADQMLQLDQMLQML GLDRCLVPSEWVRVLIHL AQRRGYRSNSTAEAAKDQ ETGAVKQALSANEALMKE KNYRTVGEMFCKDEKFTL TMPDGRTIRKTRNSPNSY RFTVTRDMVEAEAKLLFE KQRLFGNEYASAAFEEAY LAILLGQRNFDEGPGGNS PYRNLDER GACFELRYFYKFYKTFYLL Petition 870250090553, on 10 / 03 / 2025, page. 210 / 262 207 / 251 Cat. SEQ ID NO: Descrição Tipo Organismo Outras Informações Sequência NHIRLVSNETHPTGLNQQ QREQIIALAMKTANLNYK KIRNELQIPDGLRFNMVR YETEKPAEEYEKKMKFSE MQSYHKIKKVLGSSFRSL SAEQLDEIGEILSLYKSD KRRRENLEQLGLTAELIE PLLSLSFSKAGNLSLTAM RKLIPYLEQGVNYSDACT NVYGDHRAHIGAQKTKLL SYNRLREDGALEAITNPV VLRAVSQTIKVINAIVRK YGSPQFVNIELAREMSRN KAQRDKIADQNEKNREQN NNALKQIGEVKGARATGL NIIKYRLFCDQNEVCMYS GTKLDINRLFEPGYVDID HIIPYSCSFDDSYTNKVL VLSSENRQKGNRLPLAYM AGDAAKAAQFRIRVETTI RDYRKRQKLLKECISEEE EKRFRERNLSDTQYITRA VYNILNDYLECEPSKSKR PVRAVNGVITDYIRKRLG LKKVREDGDLHHAMDAAV IAITTEAMIQRISNYSKR REWNKKRTSDYVDPETGE LLTREAYDSKYAPDFPEP WLMFRKELEARLSEHPYD EIMRLRLPMYDAEEEIKP VFVSHMPKRKVTGPAHKD TIRSAKMPGNAVTRTALT KLKLKDGEITGYYNPDSD LLLYEALKKRLEEYKGNA EKAFAEPFHKPKRDGTPG PIVHTVKTYEKTSLHVHT NGGIAGNGTMIRIDVYYV PDDGYYFVPIYIADTVKE HLPNRAAVAHKEYEQWKP MQEDHFQFSLYPGDLVLV KGKKAIKLSLTNKDKEST AQPTVSRNEWLLYYKGAK Petition 870250090553, dated 03 / 10 / 2025, pp. 211 / 262 208 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence ISDATLEMTTHDRKYKID SMGIKRLCLMEKYAVDVL GEYHKVHLPEIRTTFR Effect ores MG21 143 Effector MG21167 unknown protein Non-cultured organism MRSIGWAGVTL LENMPDGEPFKIGDLGVR IFEKAEQPKTGASLALPR REARSARRRIRRRRHRKE RIKNLLQESGCIRREELE ALLAASGFAKDVYTLRLLE GLDRRLERDEWARVLLHL AQRRGYRSNSTAEAARDQ ETGVLKTALSANQTLMAE KHYRTVGRDFQQMFCQTGGTGGGNTG SFTVTREMVESEAHALFE AQRQHGNPFASEELEGRY CEILLSQRNFDAGPGGDS PFRQGDRRGFCTFEREEP RAFKACYTFEYFKLLQDL NHIRILSPGRNSRVLTAD ERERLTTLSMKSANLNYG QLRKELALDEMERFNTVR YHTDTVEQEQQQKKKKKKLQIQLQIQL TTLSFDRLDEIGTILGLY KSDDDRRREQLAKLEDA EIQALLPLSFSKAGNLSL TAMKKLIPHLERGVNYDE AARAVYGDHRGRTGAVRT KTLSYGALREEGALDEIT NPVVLRAVSQTCKVNAV VRRYGSPQAVHIELAREM SRNFQQMDQQQDQQDQDQDK AANDRAMEQIEEIKGARA TGQDLVKWKLFREQNEVC LYSGVKLDSARLFEPGYV DVDHIVPYSLCFDDGYRN KALVLASENRQKGNRLPL EYMAGDLEKKERFITLVE TTVRDYRKRQRLLKKELT EEDLEGFKERNLSDTQYIND TRAVYLKYLLKYLLT Petition 870250090553, dated 03 / 10 / 2025, pp. 212 / 262 209 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence PFGKKPVRAVNGAVTDYM RKRLGLRKNRADGDLHHA MDAAVVAIATDRMIQRIS NYAKRREWGQKVWGNYVD PETGELLTQAAFDEKYAP SFPPPWPQFRQELDPELDPHIRDPHLDPHLDPH EVVRPVFVSRMPNRKASG AAHKETIRSGRLPGYSIV KTALTDLKLDKNGEIKDY YDPSSDRLLYEALREQLK QFGGDGKKAFDEPFHKPK RDGTPGPVVNKVKTCGKS SLNVAACGGIADNGGMVR IDVFHVEDDGYYFVPYTQPQQLPQVPQVVKVKVKKS SLNVAACGGIADNGGMVR AENWKEMRDEDFLFSLYA GDLIHIVRKKPIVLKATN KDSTGEPELLRTEWMLYY NGADIATASIIASTHDRK YTGRGIGLKTLQTIEKYE VDPLGEYHKVHIPEKRQT FR Efet ores MG21 144 Efetor MG21168 proteíndo organic descondo não culdo MNYTLGLDIGIASIGWAV LKNNEQGLPCKIEDLGVR IFEAAEHPKTGASLALPR RQARGTRRCIRRRQHRKE RIKNLIEAVGLMKKEDMS VLFENSGFAKDVYDLRSE ALDRALTADEWVRVLIHL SQRRGYRSNSKAEEAKDA ENGVLKAEMQEQTAGKFKFKGT IGADGKLWRTTRNSSGDY KFTVTRQMVSDEVTHLFD SQRCMGNPFAGEEFEQKY SEILFSQRNFDEGPGGES PYRQMDLRGYCRFEKEER RAFKACYTFEHFKLLQDL NHIRIRSKDDERELLPEE RERIIALAMKSENLNFLR FLRNVLKLENT Petition 870250090553, of 03 / 10 / 2025, p. 213 / 262 210 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence NKETAELSEKNTKFTQMQ SYHKIRKALDRISKGYID TLSRGVLDDIGTILSLYK ADSKRISALRAIGLDEPV ITQLLPLSFSKAGNLSLT AMQKLIPELKKGNTYDKA CTNVYGEFQGHTVGVRRK TISLNPEFLAESGLNDKI TNPVVLRAISQTCKVVNA IVRKYGSPQMIRLELARE MSKNHDERIKAEKSMEEN RKKNENAMEHIREIKRDY ATGLDLVKWKLYQEQDGI CLYSGTHLDASRLFEDGY VDIDHIIPYSISFDDSYR NKVLVRSSENRQKGNRLP LQYMENDPQKAAAFETLV ETRIRDYRKRQNLLKKNL TDEDKSGFRRRNLNDTQY ITRTVYNLFRDYLEFAPS IYHGKEQIMAVNGAVTDY MRKRFGLHKNRADGDKHH AMDAAVIAVTTDAMIQRI SNYAKRREWGQKVQGQYV DPENGELLSQADFDEKYA PTFPEPWPQYRRELEARM GDTPMEDLERLHLPTYDP DEEVRPIFVSQMPRRKVT GAAHLETIWSKKEEGSLI KKVPLTALKLGSDGEIKN YYRPGDDPRLYDALQARL RECNGDAAKAFSEPFHKP KKDGTPGPVVNKVKIQEK TTKNVEVNGGIAGNGSMV RVDVFHVENDGYYFVPIY TADTVKMELPIKACVAGK NVDNWKVMRDEDFIFSLY AGDLIHIESTGTLKLKKT HKDADGELELVRQDAYLY YGGADISTVSWSATTHDR KYSCRGIGIKRLKCIEKY Petition 870250090553, dated 03 / 10 / 2025, pp. 214 / 262 211 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence EVDVLGGYHKVAYPEKRQ TFR Effector MG21 145 Effector MG21169 uncultured protein Uncultured organism MHYTLGLDIGISSIGWAV LQNDLGSFGEMFGVRQ IFEKAEQPKTGASLALPR REARSARRRLRRRRHRKE RIKELLQQAGCIDHGALD ALLTASGFEKDVYTLRAE GLDRQLTREEWARVLLHL AQRRGYRSNSTVEAAKDQ KTGVLKTALSANQNLMEA KGYRTAGEMFCLDEKFQM IGPDGQNTREVTLVDLVDVDLVDVDLV SQRRHGSSYASENRY CEILLSQRDFDAGPGGNS PFQRGGPRGNCTFERTEP RAFKACYTFEYFKLLQDM NHIRIQSAGHPSRGLTAD ERERLTTLAMKSANLHYG QLRKELALSKEERFNTVR YQSDDAETAEKKTKFQEM QSKHKVYGGVYKVYG ATLSHDQLDKIAEVLSLY KSDKRRKEQLSGLELEDS VIEALLPLSFSKVGSLSL DAMKKMIPYLEKGVNYDE AASAVYGDHRGHFEKTRT ATLSYGELQRQGALDSIT NPVVLRAISQTCKVNAV VRRYGPPQAVHIELAREM SRNQRQRQIDQRQID AANERLIKQVEEIKGSRA TGQDLVKFKLFRDQNEVC LYSGTKLRAERLFEPGYV DVDHIVPYSICFDDGYRN KALVLASENRQKGNRLPL EYMAGDAEKTARFMTLVE CSVRDYRQRLLKQKLT DEDLEGFKERNLSSDTQYDHFYDPHELL PFAKPVRAVNGAVTDYM Petition 870250090553, of 03 / 10 / 2025, p. 215 / 262 212 / 251 Cat. SEQ ID NO: Descrição Tipo Organismo Outras Informações Sequência RKRLGLHKNRADGDLHHA MDAAVVAITTDRMIQRIS NYAKRREWGKKVWGNYVD PETGELLSQEAFDEKYAP FFPPPWPQFRQELEARLA PDPDAEIRLLHLPHYDPE QVVQPVFVSRMPNRKVSG AAHKETIRSGKMLGYSIV KTALTDLKLDKNEEIKDY YDPSSDRLLYEALREQLK LFGGDGKKAFAQEFHKPK KDGTPGPVVNKVKTYGKS SLNVAACGGIADNGGMVR IDVFHVEDDGYYFVPIYT ADTVKDILPQRAVVAHKP KEEWKEMQDENFLFSLYS GDLVFVSSKRFITMNLNK DLKKQGATGEPVLQRKEW MAYYVGADISSGSISIEV HDRKYNQQSLGFKTLLSI EKYEVDPLGKYHRVHTPE KRQTFH Efet ores MG21 146 Efetor MG21170 protein a desconh ecido organism o não cultivad o MFCFLTKRYINDIIININ VCEKGGKMNYRIGLDIGI TSVGWAVIEDDLDGNPIR IVDLGSRIFDAAEVPKTG APLAEARRNARGARRRNR RKVHRIKRTKELLLKSSI ISKEELEKIYTNIKYNIY ELRVAGLDRKLREDELAR VLLNLVKKRGYKSNSKSA EEKDIKENAKALKAISDN RNLMKEKGYRSVAEMYLK DKKFKLTLQDGSVVCDGN GIPVIKIRNSVDDYKTTV ERSLLLDEISKILTVQKS FNPKITDEFIQEYINIFS SQRNYDEGPAFPSKYGGN LIENMLGNCTFERNEKRA PKSTYSFEMFKLLQDLNS IRIQKVNLLKSNKGNVYH KSEQSRNLNDDEKSIILE Petition 870250090553, dated 03 / 10 / 2025, pages 216 / 262 213 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence ALKLTSELSYARIRKLIN LPYDSIFNIIDYDFRNTD LTIEEIINKTEKETKNKL VEFQSFHKIRKALDNYEK NYISSLDWDTLDKIAIIL TLYKSDEKRIDKLSQMGL PSKVIDKLLPLSFSKVGH LSIVALKKLIPYLKEGVT YDKAASMVYGDFRGKINT EKKLKLSLRDIEEITNPV VRRGVSQAIKVLNAITLK YGKPDLVNIELARELSKN FADRKRQEKEMVSNMEAN QKIINEIKGNLLKENITG IDIVKYKLWTEQDGRSPY SGEVIPLELLFTKDVDID HIIPYSKCFNDGYNNKVL VKSSENRMKTNRTPLEYL TDTNQDTQMYISRVMAMY AGNRKKRDNLLKEHFTEE DEQKFKERNLKDTEYISR VVLNLISKQLDFKPNSNI AENKRAMAVKGGITDQIR KRLNIVKVRDNDIHHAID ATIVAITTESMIQKITRF FKNKENRDNDNNISKEQY YETFPQPYKNFELELKAR LLGNEEDIKTQLEKLDIL EYKLHGYPKPIFVSRMPK RKVRGSAHMETIRGIGKN GMLITKTNLSDLKLNKEN EIEGYYNKQDDRLLYEAL RSRLIEYNNDAKEAFKEP FFKPKSDGTKGPIVKKVK IESPSSKNVYLSKMHGAA GNGDTVRIDVFFVEGEGY YFIPIYVADTIKQELPNK APVAHKNYEEWKEMDEKD FIFSLYPGDLVYVKSKGN INLVPMAKDSKRKNICVN EMLGYYIKCNISSANISI STHDRMYWQDSLGVKRLL Petition 870250090553, dated 03 / 10 / 2025, pp. 217 / 262 214 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence ELKKYQVDVLGNYSEVKL PEKRMKFNLKKVKGEKIS YS trac rRNA MG17 1 147 tracrRN A MG171-1 nucleot idea AAGGTCATAGGACCGTAA AGCTCTGACGCCCTGTCT TATGACAGGGCGTCATCT TTT trac rRNA MG17 1 148 tracrRN A MG171-2 nucleot ídeo artific ial TTATACCATACCAAGAAC TATTATGGTTACTATGAT AAGGATCATAGGACCAGCTGACCGCCCG TTTGGCAGGGCGTCATCT TTT trac rRNA MG17 1 149 tracrRN A MG171-3 nucleot ídeo artific ial TTATACCATACCAAGAAC TATTATGGTTGCTATGAT AAGGTCATAGGACCGTAA AGCTCTGACGCCCTGCTA TTTGGCAGGCT TGGTCTT107 rRNA107 tracrRN A MG171-4 nucleot ideo artific ial TTATACCATACCAAGAAC TATTATGGTTGCTATGAT AAGGTCATAGGACCGTAA AGCTCTGACGCCCTGCTG TTTGGCAGGGCGTCATCT TTT trac rRNA MG17 1 1 151 tracrRN A MG117 nucleotide TTATACCATACCAAGAAC TATTATGGTTGCTATGAT AAGGTCATAGGACCGTAA AGCTCTGACGCCCTGCTA TTTGGCAGGGCGTCATCT TTT CRIS PR repeat MG17 1 152 CRISPR repeat MG171-1 nucleotide ideaartificial CATAGTTCCCTAATAGCT CTTGGTATGGTATAAT Petition 870250090553, dated 03 / 10 / 2025, pp. 218 / 262 215 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence Repeat 153 Artificial nucleotide repeat GTCATAGTTCCCTAATAG CRISPR MG17 1 CRISPR MG171-2 ion CTCTTGGTATGGTATAAT Repeat 154 Artificial nucleotide repeat GTCATAGTTCCCTAATAG CRISPR MG17 1 CRISPR MG171-3 ion CTCTTGGTATGGTATAAT Repeat 155 Artificial nucleotide repeat GTCATAGTTCCCTAATAG CRISPR MG17 1 CRISPR MG171-4 ion CTCTTGGTATGGTATAAT Repeat 156 Artificial nucleotide repeat GTCATAGTTCCCTAATAG CRISPR MG17 1 CRISPR MG171-5 ial ide CTCTTGGTATGGTATAAT trac 157 tracrRN artificial nucleot TGGGAGATCGGGGCACGC rRNA MG17 7 A MG177-1 ial ide GGTTTAGCTGCGTGAGGA ACCGTTAACAAGCCTTCA GGGCACCAAATCGGGGAG CAGGCTACGGCCTGCTT trac 158 tracrRN artificial nucleot ATTGTAGTCGATGGGAGA rRNA MG17 7 A MG177-2 ial ide TCGAGAAGCTTCCGTTAA CAAGCTTTAGCAAAAGAT Petition 870250090553, dated 03 / 10 / 2025, pp. 219 / 262 216 / 251 Cat. SEQ ID NO: Organism Type Description Other Information Sequence GAGGAGGCGAGCTACGGC TCGTCTCTTTCCTTTT trac rRNA MG17 7 159 tracrRN A MG177-3 nucleotide TGAGGAGGCGAGCTACGG CTCGTCTCTTTCTTTT trac rRNA MG17 7 160 tracrRN A MG177-4 nucleot ídeo artific ial ATTTAGCCGATAGGAGAT CGCGCGCCGTTCCCAAGG CCTCCGGGCCGAGGAACC GTTAACAAGGATAAAATTTGCCGACCGACCGAGCCGAGCCGATT TGCTTT trac rRNA MG17 7 161 tracrRN A MG177-5 nucleot ideo artific ial AGCCGATGGGAGATCGGG GGCCAGCCGTTAACAAGC TGAGGGGCAGTGCCTCGC GCAATGCCCCAAGATGCA CAAAATGCAAGGGCGGCC TACTGCCGGC 127 tracGRNA tracrRN A MG177-6 nucleot ideo artific ial CCGACAGGAAATCGCGGA CCAGCCGCAACCACGTAC TCTTCTTAAAAGGGTTCG TTGCATTAGAACCGATTC TGTGGCGGAATGTCAAAG AACCAGTATTTT trac rRNA MG17 7 7 163 tracrRN MG177 TGTAACCGAATGGAGAAC GGGGAACTTTGGGGAGTC CGCTTTTGTGGATGAACC AACCGTTAACAAGTGCAA GAAGCTTGTGCAACAAAT TAGGGGGCTTGCTACGGC TTGCCCCTTTT Repetition isCRISPR MG17 7 164 CRISPR MG177-1 repeat artificial nucleotide GTTGCGTTCCTCCCCGA TCTCCCATCG Petition 870250090553, dated 03 / 10 / 2025, pp. 220 / 262 217 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence CRISPR Repeats MG17 7 165 CRISPR Repeat MG177-2 artificial nucleotide GTTGCGGTTGCTCCTCGA TCTCCCATCGGCTACAAT CRISPR Repeats MG17 7 166 CRISPR Repeat MG177-3 artificial nucleotide GTTGCGGTTGCTCCCCGA TCTCCATCGGCTATAAT CRISPR Repeats MG17 7 167 CRISPR Repeat MG177-4 artificial nucleotide GGCGCGCGATTTCCTATC GGCTAAATT CRISPR Repeats MG17 7 168 CRISPR Repeat MG177-5 artificial nucleotide GTTGGCGGCTGGCCCCCGA TCTCCCATTAGCTAAACT CRISPR MG17 7-6 Repeats CRISPR MG177-6 artificial nucleotide GTTGCGGCTGGTCCGCGA TTTCCTATCGGCTAAACT Petition 870250090553, dated 03 / 10 / 2025, pp. 221 / 262 218 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence CRISPR Repeats MG17 7 170 CRISPR Repeat MG177-7 artificial nucleotide GTTCCCCGTTCTCCATTC GGCTACACT trac rRNA MG18 3 171 tracrRNA MG183-1 artificial nucleotide TATCAGGCGTTCCGATGG TGGGGACTATCGGCAACA AGTCGTCCCGGGCAACTG GGCGACACCGATACAAAA CGGCTGCTTCGGCAGCCG TTTT trac rRNA MG18 3 172 tracrRNA MG183-2 artificial nucleotide TTGTATCACATGTTCCGA TGGTGGGGACTATCGGCA ACAAGGCATTAAATGCCG ACAAAGTCGCCTGAAGCA AGCTTCGGCTTGCAAGGC GCAACTCCTTGAATAGAC GCCCAGTTTCGGCTGGGC GTTTT trac rRNA MG18 3 173 tracrRN A MG183-3 artificial nucleotide TATCAGGCATTCCGATAG GTGGGGACTTATCGGCAA CTAGGCCTTACCGAAAGG GAAGGCCGCCCGATACGG GGCACCAGGTCTCGGCCT GGTGCCCCAAGTCTTTT trac rRNA MG18 3 174 tracrRN A MG183-4 artificial nucleotide ATGGTATCAGACGTTCCG CTGGTGAGGAACTCTATC GGCAACAAGGCATTTGAA TGCCGAAAAACAGCGCCC GGTCTTGGCCGGGCGTTT T trac rRNA MG18 3 175 tracrRN A MG183-5 artificial nucleotide ATTCTATCAGATGTTCCA CTGGTGAGGAACTCTATCGGCAACAAGGTATTTTAT GCCGACAAGATAGAGCAT ACCAGTTTCGGCTGGAAT GTTCGCCTTAAACGCCCG GTTTCGGCCGGGCGTTTT Petition 870250090553, dated 03 / 10 / 2025, pages 222 / 262 219 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence trac rRNA MG18 3 176 tracrRN A MG183-6 artificial nucleotide CGTATCAGGTTTTCCGAT GGTGGGGACTATCGGCAA CAAAGCATTTCTAATGCT ACCGATACAAACGGCCTC TTCGGAGGCCGTTTT trac rRNA MG18 3 177 tracrRN A MG183-7 artificial nucleotide TATCAAGCATTCCGATGG TGGGGACTATCGGTAACA AGCATTTTTGCACCGATA CAAAACGGTCGCTTCGGC GGCCGTTTT trac rRNA MG18 3 178 tracrRN A MG183-8 artificial nucleotide TATCAAGCATTCCGATGG TGGGGACTATCGGTAACA AGTGTTTATCACACCGAT ACAGAACGGTCGCCTCGG CGGCCGTTTT trac rRNA MG18 3 179 tracrRN A MG183-9 artificial nucleotide TGTATCAGGTGTTCCGAT GGTGGGGACTATCGGCAA CAAGGCCTTAAAAGGCCG CCCGATACGGGCGTCAGG TTTCGGCCTGGCGCCCTA CTTTT trac rRNA MG18 3 180 tracrRN A MG18310 artificial nucleotide TATCAAGCATTCCGATGG TGGGGACTATCGGTAACA AGTGTTTATCACACCGAT ACAAAACGGCTGCTTCGG CGGCCGTTTT trac rRNA MG18 3 181 tracrRN A MG18311 artificial nucleotide TGTATCAAGCATTCCGAT GGTGGGGACTATCGGTAA CAAGTGTTTATCACACCG ATATAGAACGGTCGCTTC GGGGCCGTTTT tracerRNA MG18 3 182 tracrRN A MG18312 artificial nucleotide GTGTATCAAGCATTCCGA TGGTGGGGACTATCGGTA ACAAGCATTATTGCACCG ATACAAAACGGTCGCTTC GGCGACCGTTTT trac rRNA MG18 3 183 tracrRN A MG18313 artificial nucleotide GTATTAGGCGTTCCGATG GTGGGGACTGTCGGCAAC AAGTCGATAGGGTTTCGG CCCTTACGACACCGATAC Petition 870250090553, dated 03 / 10 / 2025, pp. 223 / 262 220 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence AAAAGGGCTCCTTCGGA GCCCTTTT trac rRNA MG18 3 184 tracrRN A MG18314 artificial nucleotide GTATTAGGGTGTTCCGATG GTGGGGACTATCGGCAAC AAGGGCGGATGCGCTCCCT CGGGGGCGCGGACGCCGT CGATACCGAAAGGCTGCT TCGGCAGCCTTTCGCTTT T trac rRNA MG18 3 185 tracrRN A MG18315 artificial nucleotide CTATCGAGCGTTGCGGTG GTGGGGACTGTCGGCAAC AAGTCTAGGGAGCTTGCT CCTGAAGACACACAAATAAG AAACGGGCACTTCGGTGC CCGTTT trac rRNA MG18 3 186 tracrRN A MG18316 artificial nucleotide TATCAAGCATTCCGATGG TGGGGACTATCGGTAACA AGCAGTATTGCATCGATA CAAAACGGTCGCTTCGGC GACCGTTTT trac rRNA MG18 3 187 tracrRN A MG18317 artificial nucleotide GTATCAAGCATTCCGATG GTGAGGACTGTCGGCAAC AAGTCGATGAGACCTCGG TCTCTACGACACCGATAC AAAGGGTTCCTTCGGGAA CCCTTTT trac rRNA MG18 3 188 tracrRN A MG18318 artificial nucleotide TATCAGGCGTTCCGATGG TGGGGACTATCGGCAACA AGCCCTCAGGGGCACCGA TACAAACGGCCTCCTTCG GGAGGCCGTTTT trac rRNA MG18 3 189 tracrRN A MG18319 artificial nucleotide TATCAGGCGTTCCGATGGTGGGGACTATCGGCAACA AGCCCTTCGGGGCACCGA TACAAACGGCTTCCTTCG GGAGGCCGTTTT trac rRNA MG18 3 190 tracrRN A MG18320 artificial nucleotide GTGTCAAGTGTTCCGATG GTGGGGACTGTCGGCAAC AAGTCGTGGGCTTCGGCC CTACGACACCGATACAAA Petition 870250090553, dated 03 / 10 / 2025, pp. 224 / 262 221 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence AGGGCTTCTTCGGAAGCC CTTTT trac rRNA MG18 3 191 tracrRN A MG18321 artificial nucleotide GTATCAAGCGTTCCGATG GTGGGGACTGTCGGCAAC AAGTCGTGGGCTTCGGCC CTGCGACACCGATACAAA AGGGCTTCTTCGGAGGCC CTTTT trac rRNA MG18 3 192 tracrRN A MG18322 artificial nucleotide TATCAAGCATTCCGATGG TGGGGACTATCGGTAACA AGTGTTTATCACACCGAT ACAGAACGGCTGCTTCGG CGGCCGTTTT CRISPR Repeats MG18 3 193 CRISPR Repeat MG183-1 artificial nucleotide GTTCCGATACCCCACCAT CGGAACGCCTGATAAACT CRISPR MG18 3-2 Repeats 194 CRISPR MG183-2 Repeat artificial nucleotide GTTCCGATACCCCACCCT CGGAACATGTGATACAAT CRISPR MG18 3-1 Repeats 195 CRISPR MG183-3 Repeat artificial nucleotide GTTCCGATACCCCACCAT CGGAATGCCTGATATACT 196 CRISPR MG183-4 Repeat artificial nucleotide GTTCCGATACCTCACCAG CGGAACGCCTGATACAAT Petition 870250090553, dated 03 / 10 / 2025, pp. 225 / 262 222 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence CRISPR MG18 3 Repeats of CRISPR MG18 3 197 CRISPR MG183-5 repeat artificial nucleotide GTTCCGATACCTCACCAG CGGAACATCTGATACAAT Repeats of CRISPR MG18 3 198 CRISPR MG183-6 repeat artificial nucleotide GTTCCGATACCCCACCAT CGGAAAGCCTGATACGCT C Repeats of CRISPR MG18 3 199 CRISPR MG183-7 repeat artificial nucleotide GTTCCGATACCCCACCAT CGGAATGCTTGATAAACT Repeats of CRISPR MG18 3 200 CRISPR MG183-8 repeat Artificial nucleotide GTTCCGATACCCCACCAT CGGAATGCTTGGTAAACT CRIS Repeats 201 CRISPR Repeat MG183-9 artificial nucleotide GTTCCGATACCCCACCAT CGGAATACCTGCTACACT Petition 870250090553, dated 03 / 10 / 2025, pp. 226 / 262 223 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence PR MG18 3 CRISPR Repeats PR MG18 3 202 CRISPR Repeat MG18310 artificial nucleotide GTTCCGATACCCCACCAT CGGAATGCTTGGTAAACT CRISPR Repeats PR MG18 3 203 CRISPR Repeat MG18311 artificial nucleotide GTTCCGATACCCCACCAT CGGAATGCTTGCTACACT CRISPR Repeats PR MG18 3 204 CRISPR Repeat MG18312 artificial nucleotide GTTCCGATACCCCACCAT CGGAATGTTTGATAGACT CRISPR Repeats PR MG18 3 205 CRISPR Repeat MG18313 nucleotide Artificial GTTCCGATACCCCACCAT CGGAACGCCTGATACACT C CRISPR Repeats 206 CRISPR Repeat MG18314 artificial nucleotide GTTCCGATACCCCACCAT CGGAACACCTGTTACTCT C Petition 870250090553, dated 03 / 10 / 2025, pp. 227 / 262 224 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence MG18 3 CRISPR Repeats MG18 3 207 CRISPR Repeat MG18315 artificial nucleotide GTTCCGATACCCCACCAC CGGAACGCTTGATAGACT C CRISPR Repeats MG18 3 208 CRISPR Repeat MG18316 artificial nucleotide GTTCCGATACCCCACCAT CGGAATGCTTGATAAACT CRISPR Repeats MG18 3 209 CRISPR Repeat MG18317 artificial nucleotide GTTCCGTCACCTCACCAT CGGAACGTTTGATACACT C CRISPR Repeats MG18 3 210 CRISPR Repeat MG18318 nucleotide Artificial nucleotide GTTCCGATACCCCACCAT CGGAACGCCTGATAAACT CRISPR 211 repeats CRISPR MG18319 repeat artificial nucleotide GTTCCGATACCCCACCAT CGGAACGCCTGATAAACT Petition 870250090553, dated 03 / 10 / 2025, pp. 228 / 262 225 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence MG18 3 CRISPR Repeats MG18 3 212 CRISPR Repeat MG18320 artificial nucleotide GTTCCGATACCCCACCAT CGGAACACTTGATACACT C CRISPR Repeats MG18 3 213 CRISPR Repeat MG18321 artificial nucleotide GTTCCGATACCCCACCAT CGGAACACTTGATACACT C CRISPR Repeats MG18 3 214 CRISPR Repeat MG18322 artificial nucleotide GTTCCGATACCCCACCAT CGGAATACTTGGTAAACT tracrRNAs MG21 215 tracrRNA MG21163 artificial nucleotide TTATACCACTACGAGAGA CCATTGTGTTACTGCAAT AAAGTAGAACACTGTGAA GCTCTGCCCCAGCCTTCG GTTGGGGCATCTTT trac rRNA s MG21 216 tracrRN A MG21164 artificial nucleotide TACCACAACAAGAGACAT CAGGTTACTGCAATCAGG CAGTATGCCTCGAAGCTC CGCCCCGACCACAGCTTT GTGGTCGGGGCGTCTTCG TTGTATGGAAACTGTTG trac rRNA s MG21 217 tracrRN A MG21165 artificial nucleotide ATACCACTACGAGAGAGA AAATGTGTTATCACAATA AGGTTGTAACACCGCAAA GCTCTGCCCCGATCATGA Petition 870250090553, dated 03 / 10 / 2025, pp. 229 / 262 226 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence TCAGGTCGGGGCATCTTT GTTTT trac rRNA s MG21 218 tracrRN A MG21166 artificial nucleotide TTGTACCACAGCAAGAAA CATTTGGTTACTGCAATA AAAAGGCAGTATGCCGCA GAGCTCCGCCCCAGCCAC TTTTGTGGTTGGGGCGTC TCTGATTTT trac rRNA s MG21 219 tracrRN A MG21167 artificial nucleotide TTGTACCACAACAAGAGA TTTTAGGTTACTGCGATC AGGCAGTATGCCTCAAAG CTCCACCCCAACCACGTT TTGTGGTTGGGGTGTCTT TGTTTT trac rRNA s MG21 220 tracrRN A MG21168 artificial nucleotide TTGTACCACAACAAGAGA CTTTAGGTTACTGCAATC AGGCAGTATGCCTCAGAG CTCCGCCCCGACCACTTG ATTGTGGTTGGGGCGTCT TT trac rRNA s MG21 221 tracrRN A MG21169 artificial nucleotide CTTATACCACAACAAGAG ATTTTAGGTTACTGCGAT CAGGCAGTATGCCTCGAA GCTCCACCCCAACCACAT TTGTGGTTGGGGTGT trac rRNA s MG21 222 tracrRN A MG21170 artificial nucleotide ATTATATCATAAAATAGA GCACTAGGTTAGTATAAT AAGGCCTTGTGCCGTAGA GTAACAAACCACTACTTT TTAGTAGTGGTTTT CRIS PR repeats MG21 223 CRISPR repeat MG21163 artificial nucleotide ialGTTGTAGTTCCCTTTGGT CTCTCGTAGTGGTATAAT 224-repeat CRISPR repeat artificial nucleotide GTTGTAGTTCCCTGATGT CTCTTGTTGTGGTATAAT Petition 870250090553, dated 03 / 10 / 2025, pages 230 / 262 227 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence CRISPR MG21 MG21164 CRISPR Repeats MG21 225 CRISPR Repeat MG21165 artificial nucleotide GTTGTGGGTTCCCTTTTCT CTCTCGTAGTGGTATAAT CRISPR Repeats MG21 226 CRISPR Repeat MG21166 artificial nucleotide GTTGTAGTTCCCAGATGT TTCTTGCTGTGGTATAAT CRISPR Repeats MG21 227 CRISPR Repeat MG21167 artificial nucleotide GTTGTAGTTCCCTGAAGT CTCTTGTTGTGGTATAAT CRISPR Repeats MG21 228 CRISPR Repeat MG21168 nucleotide Artificial nucleotide GTTGTAGTTCCCTATTGT TTCTTGTTGTGGTATAAT CRISPR repeats MG21 229 CRISPR repeat MG21169 artificial nucleotide GTTGTAGTTCCCTGAAGT CTCTTGTTGTGGTATAAT Repeats 230 CRISPR repeat artificial nucleotide GTTATACTTCCCTATTGT TTTATTTTATGATATAAT Petition 870250090553, dated 03 / 10 / 2025, pages 231 / 262 228 / 251 Cat. SEQ ID NO: Description Type Organism Other Information CRIS Sequence PR MG21 MG21170 MG17 1 scaf fold s de sgRN A 231 MG171-1 scaffold d de sgRNA longo nucleot ídeo artific ial CAUAGUUCCCUAAUAGGA AACUAUUAUGGUUGCUAU GAUAAGGUCAUAGGACCG UAAAGCUCUGACGCCCUG UCUUAUGACAGGGCGUCA UCUUUU MG17 1 scaf fold s de sgRN A 232 MG171-1 scaffold d de sgRNA curto nucleot ídeo artific ial CAUAGUUCCCUAAUGAAA AUUAUGGUUGCUAUGAUA AGGUCAUAGGACCGUAAA GCUCUGACGCCCUGUCUU AUGACAGGGCGUCAUCUU UU MG17 1 scaf fold s de sgRN A 233 MG171-2 scaffold d de sgRNA longo nucleot ídeo artific ial GUCAUAGUUCCCUAAUGA AAAUUAUGGUUACUAUGA UAAGGUCAUAGGACCGUA AAGCUCUGACGCCCUGCC GUUUGGCAGGGCGUCAUC UUUU MG17 1 scaf fold s de sgRN A 234 MG171-2 scaffold d de sgRNA scuto nucleot ídeo artific ial GUCAUAGUGAAAACUAUG AUAAGGUCAUAGGACCGU AAAGCUCUGACGCCCUGC CGUUUGGCAGGGCGUCAU CUUUU MG17 1 scaf fold s de sgRN A 235 MG171-3 scaffold d de sgRNA long nucleot ídeo artific ial GUCAUAGUUCCCUAAUGA AAAUUAUGGUUGCUAUGA UAAGGUCAUAGGACCGUAAAGCUCUGACGCCCUGCU AUUUGGCAGGGCGUCAUC UUUU MG17 1 236 MG171-3 scaffold artificial nucleotide GUCAUAGUGAAAGCUAUG AUAAGGUCAUAGGACCGU Petition 870250090553, dated 03 / 10 / 2025, pp. 232 / 262 229 / 251 Cat. SEQ ID NO: Description Type Organism Outras Information Sequence sgRNA fold sgRN short sgRNA fold AAAGCUCUGACGCCCUGC UAUUUGGCAGGGCGUCAU CUUUU MG17 1 sgRN fold s A 237 MG171-4 sgRNA long nucleot Artific ial GUCAUAGUUCCCUAAUGA AAAUUAUGGUUGCUAUGA UAAGGUCAUAGGACCGUA AAGCUCUGACGCCCUGCU GUUUGGCAGGGCGUCAUC UUUU MG17 1 foldable shelf sgRN A 238 MG171-4 sgRNA shelf curto nucleot Artific ial idea GUCAUAGUGAAAGCUAUG AUAAGGUCAUAGGACCGU AAAGCUCUGACGCCCUGC UGUUUGGCAGGGCGUCAU CUUUU MG17 1 fold sgRNA shelf A 239 MG171-5 sgRNA long nucleot shelf Artific ial GUCAUAGUUCCCUAAUGA AAAUUAUGGUUGCUAUGA UAAGGUCAUAGGACCGUA AAGCUCUGACGCCCUGCU AUUUGGCAGGGCGUCAUC UUUU MG17 1 scaffold fold sgRN A 240 MG171-5 scaffold d de sgRNA curto nucleot ídeo artific ial GUCAUAGUGAAAGCUAUG AUAAGGUCAUAGGACCGU AAAGCUCUGACGCCCUGC UAUUUGGCAGGGCGUCAU CUUUU MG17 7 scaf fold s de sgRN A 241 MG177-2 scaffol d de sgRNA longo nucleot ídeo artific ial GUUGCGGUUGCUCCUCGAGAAAUCGAGAAGCUUCCG UUAACAAGCUUUAGCAAA AGAUGAGGAGGCGAGCUA CGGCUCGUCUCUUUCCUU UU Petition 870250090553, dated 03 / 10 / 2025, pages 233 / 262 230 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence MG17 7 scaffold s of sgRN A 242 MG177-2 scaffold d of short sgRNA artificial nucleotide GUUGCGGUUGCUCCUGAA AAGAAGCUUCCGUUAACA AGCUUUAGCAAAAGAUGA GGAGGCGAGCUACGGCUC GUCUCUUUCCUUUU MG17 7 scaffold s of sgRN A 243 MG177-3 scaffold d of long sgRNA artificial nucleotide GUUGCGGUUGCUCCCCGA UGAAAAUCGAGGAGCUUC CGUUAACAAGCUUUCGGC ACAAAAUGAGGAGGCGAG CUACGGCUCGUCUCUUUC UUUU MG17 7 scaffold s of sgRN A 244 MG177-3 short sgRNA artificial nucleotide scaffold d GUUGCGGUUGCUCCGAAA GGAGCUUCCGUUAACAAG CUUUCGGCACAAAAUGAG GAGGCGAGCUACGGCUCG UCUCUUUCUUUU MG17 7 sgRN fold fold s of sgRN A 245 MG177-4 long sgRNA artificial nucleotide scaffold ial GGCGCGCGAUUUCCGAAA GGAGAUCGCGCGCCGUUC CCAAGGCCUCCGGGCCGA GGAACCGUUAACAAGGAU AAAUGUCCACAAAAUCGG AAGGCGGGCUACGGCCCG CCUUCCUGCUUU MG17 7 scaf fold s of sgRN A 246 MG177-4 scaffold of sgRNA short artificial nucleotide GGCGCGCGAUGAAAAUCG CGCGCCGUUCCCAAGGCC UCCGGGCCGAGGAACCGUUAACAAGGAUAAAUGUCC ACAAAAUCGGAAGGCGGG CUACGGCCCGCCUUCCUG CUUU MG17 7 scaf folds of 247 MG177-5 scaffold of sgRNA long artificial nucleotide GUUGCGGCUGGCCCGAAA GGGCCAGCCGUUAACAAG CUGAGGGGCAGUGCCUCG CGCAAUGCCCCAAGAUGC ACAAAAUGCAAGGGCGGG CUACGGCCCGCCCUUU Petition 870250090553, dated 03 / 10 / 2025, pages 234 / 262 231 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence sgRN A MG17 7 scaffold s of sgRN A 248 MG177-5 scaffold d of short sgRNA artificial nucleotide GUUGCGGCUGGAAACAGC CGUUAACAAGCUGAGGGG CAGUGCCUCGCGCAAUGC CCCAAGAUGCACAAAAUG CAAGGGCGGGCUACGGCC CGCCCUUU MG17 7 scaffold s of sgRN A 249 MG177-6 scaffold d of long sgRNA artificial nucleotide GUUGCGGCUGGUCCGAAA GGACCAGCCGCAACCACG UACUCUUCUUAAAAGGGU UCGUUGCAUUAGAACCGA UUCUGUGGCGGAAUGUCA AAGAACCAGUAUUUU MG17 7 scaffold s of sgRN A 250 MG177-6 short sgRNA scaffold artificial nucleotide GUUGCGGCGAAAGCCGCA ACCACGUACUCUUCUUAA AAGGGUUCGUUGCAUUAG AACCGAUUCUGUGGCGGA AUGUCAAAGAACCAGUAU UUU sgRN A MG21 -1 directed to HAO1 human no 251 MG21-1 hHAO1sgRNAE4 artificial nucleotide mC*mC*mC*rGrUrUrCr CrCrArGrGrGrArCrUr GrArCrArGrGrGrUrUr GrUrArGrUrUrCrCrCr CrUrUrUrUrGrArArAr ArArArArGrUrGrUrGr UrUrArCrUrGrCrArAr UrArArGrGrUrArArAr ArCrArCrCrArCrGrAr ArGrCrUrCrUrGrCrCr CrUrArArCrUrGrCrCr UrUrArGrCrArGrUrUrArGrGrGrCrArUrC*mU *mU*mU sgRN A MG21 -1 252 MG21-1 hHAO1sgRNAF1 artificial nucleotide mC*mU*mA*rUrArUrAr UrGrArCrUrArUrUrAr CrArGrGrUrCrGrUrUr GrUrArGrUrUrCrCrCr Petition 870250090553, dated 03 / 10 / 2025, pages 235 / 262 232 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence directed to human HAO1 CrUrUrUrUrGrArArArArArArArGrUrGrUrGr UrUrArCrUrGrCrArAr UrArArGrGrUrArArArArCrArCrCrArCrGrAr ArGrCrUrCrUrGrCrCr CrUrArArCrUrGrCrCr UrUrArGrCrArGrUrUr ArGrGrGrCrArUrC*mU *mU*mU sgRNA A MG21-1 directed to human HAO1 253 MG21-1 hHAO1sgRNAF9 artificial nucleotide mC*mC*mA*rGrArArAr UrUrGrUrGrGrArGrGr CrUrGrUrGrGrGrUrUr GrUrArGrUrUrCrCrCr CrUrUrUrUrGrArArAr ArArArArGrUrGrUrGr UrUrArCrUrGrCrArAr UrArArGrGrUrArArAr ArCrArCrCrArCrGrAr ArGrCrUrCrUrGrCrCr CrUrArArCrUrGrCrCr UrUrArGrCrArGrUrUr ArGrGrGrCrArUrC*mU *mU*mU sgRN A MG21 -1 directed to HAO1 human no 254 MG21-1 hHAO1sgRNAC6 nucleotide artificial mU*mG*mU*rGrArCrAr GrUrGrGrArCrArCrAr CrCrUrUrArCrGrUrUr GrUrArGrUrUrCrCrCr CrUrUrUrUrGrArArAr ArArArArGrUrGrUrGr UrUrArCrUrGrCrArAr UrArArGrGrUrArArAr ArCrArCrCrArCrGrAr ArGrCrUrCrUrGrCrCr CrUrArArCrUrGrCrCr UrUrArGrCrArGrUrUr ArGrGrGrCrArUrC*mU *mU*mU sgRN A MG21 -1 255 MG21-1hHAO1sgRNAB9 artificial nucleotide mA*mA*mU*rUrUrCrUr GrGrCrArGrArArCrAr UrCrArArUrCrGrUrUr GrUrArGrUrUrCrCrCr Petition 870250090553, dated 03 / 10 / 2025, pp. 236 / 262 233 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence directed to human HAO1 CrUrUrUrUrGrArArArArArArArArGrUrGrUrGr UrUrArCrUrGrCrArAr UrArArGrGrUrArArArArCrArCrCrArCrGrAr ArGrCrUrCrUrGrCrCr CrUrArArCrUrGrCrCr UrUrArGrCrArGrUrUr ArGrGrGrCrArUrC*mU *mU*mU sgRNA A MG21-1 directed to human HAO1 256 MG21-1 hHAO1sgRNAF3 artificial nucleotide mG*mA*mG*rCrUrUrGr CrCrArCrUrGrUrGrAr GrArGrGrUrArGrUrUr GrUrArGrUrUrCrCrCr CrUrUrUrUrGrArArAr ArArArArGrUrGrUrGr UrUrArCrUrGrCrArAr UrArArGrGrUrArArAr ArCrArCrCrArCrGrAr ArGrCrUrCrUrGrCrCr CrUrArArCrUrGrCrCr UrUrArGrCrArGrUrUr ArGrGrGrCrArUrC*mU *mU*mU sgRN A MG21 -1 directed at human HAO1 in 257 MG21-1 hHAO1sgRNAA2 artificial nucleotide mA*mU*mU*rArCrArGr GrUrCrUrGrGrGrGrCr ArArArUrGrArGrUrUr GrUrArGrUrUrCrCrCr CrUrUrUrUrGrArArAr ArArArArGrUrGrUrGr UrUrArCrUrGrCrArAr UrArArGrGrUrArArAr ArCrArCrCrArCrGrAr ArGrCrUrCrUrGrCrCr CrUrArArCrUrGrCrCr UrUrArGrCrArGrUrUr ArGrGrGrCrArUrC*mU *mU*mU sgRN A MG21 -1 258 MG21-1hHAO1sgRNAF4 artificial nucleotide mC*mC*mG*rUrUrCrCr CrArGrGrGrArCrUrGr ArCrArGrGrCrGrUrUr GrUrArGrUrUrCrCrCr Petition 870250090553, dated 03 / 10 / 2025, pages 237 / 262 234 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence directed to human HAO1 CrUrUrUrUrGrArArArArArArArArGrUrGrUrGr UrUrArCrUrGrCrArAr UrArArGrGrUrArArArArCrArCrCrArCrGrAr ArGrCrUrCrUrGrCrCr CrUrArArCrUrGrCrCr UrUrArGrCrArGrUrUr ArGrGrGrCrArUrC*mU *mU*mU sgRNA A MG21-1 directed to human HAO1 259 MG21-1 hHAO1sgRNAG9 artificial nucleotide mA*mA*mG*rUrCrUrUr CrCrUrGrGrArCrGrGr GrGrGrUrGrUrGrUrUr GrUrArGrUrUrCrCrCr CrUrUrUrUrGrArArAr ArArArArGrUrGrUrGr UrUrArCrUrGrCrArAr UrArArGrGrUrArArAr ArCrArCrCrArCrGrAr ArGrCrUrCrUrGrCrCr CrUrArArCrUrGrCrCr UrUrArGrCrArGrUrUr ArGrGrGrCrArUrC*mU *mU*mU sgRN A MG21 -1 directed at human HAO1 in 260 MG21-1 hHAO1sgRNAH8 artificial nucleotide mG*mU*mG*rCrCrUrUr UrCrCrGrCrArCrArCr CrCrCrCrGrUrGrUrUr GrUrArGrUrUrCrCrCr CrUrUrUrUrGrArArAr ArArArArGrUrGrUrGr UrUrArCrUrGrCrArAr UrArArGrGrUrArArAr ArCrArCrCrArCrGrAr ArGrCrUrCrUrGrCrCr CrUrArArCrUrGrCrCr UrUrArGrCrArGrUrUr ArGrGrGrCrArUrC*mU *mU*mU DNA Sequence 261 MG21-1hHAO1Target Site-E4 artificial nucleotide CCCGTTCCCAGGGACTGA CAGG Petition 870250090553, dated 03 / 10 / 2025, pp. 238 / 262 235 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Human HAO1 Target Site Sequence Human HAO1 Target Site DNA Sequence 262 MG21-1 hHAO1Target Site-F1 artificial nucleotide CTATATATGACTATTACA GGTC Human HAO1 Target Site DNA Sequence 263 MG21-1 hHAO1Target Site-F9 artificial nucleotide CCAGAAATTGTGGAGGCT GTGG HAO1 Target Site DNA Sequence 264 MG21-1 hHAO1Target Site-C6 artificial nucleotide TGTGACAGTGGACACACC TTAC Petition 870250090553, dated 03 / 10 / 2025, pp. 239 / 262 236 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Human Sequence DNA sequence of the HAO1 target site Human 265 MG21-1 hHAO1Target Site-B9 artificial nucleotide AATTTCTGGCAGAACATC AATC DNA sequence of the HAO1 target site Human 266 MG21-1 hHAO1Target Site-F3 artificial nucleotide GAGCTTGCCACTGTGAGA GGTA DNA sequence of the HAO1 target site Human 267 MG21-1 hHAO1Target Site-A2 artificial nucleotide ATTACAGGTCTGGGGCAA ATGA 268 MG21-1 hHAO1- artificial nucleotide sequence CCGTTCCCAGGGACTGAC AGGC Petition 870250090553, dated 03 / 10 / 2025, pp. 240 / 262 237 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Human HAO1 Target Site DNA Sequence Target Site-F4 Human HAO1 Target Site DNA Sequence 269 MG21-1 hHAO1Target Site-G9 artificial nucleotide AAGTCTTCCTGGACGGGG GTGT Human HAO1 Target Site DNA Sequence 270 MG21-1 hHAO1Target Site-H8 artificial nucleotide GTGCCTTTCCGCACACCC CCGT sgRNA A MG2 3-1 directed to HAO1 271 MG23-1 hHAO1sgRNAA4 artificial nucleotide mA*mG*mU*rUrArCrCr UrGrGrArArArGrCrUr ArArGrCrCrCrCrGrUrUr UrGrArGrArArCrCrUr GrArArArGrGrUrGr ArGrUrGrCrArArArUr ArArGrGrUrUrUrArAr CrCrGrArArArUrUrGr UrUrUrArCrCrUrGrCr Petition 870250090553, dated 03 / 10 / 2025, pp. 241 / 262 238 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Human sequence ArUrUrGrUrGrCrArGr UrArUrArArGrArArArAr GrArCrCrGrCrGrArGr GrUrCrU*mU*mU*mU sgRNA A MG2 3-1 directed to HAO1 human 272 MG23-1 hHAO1sgRNAH8 artificial nucleotide mU*mC*mU*rUrUrUrCr ArCrUrUrGrGrUrUrAr GrGrGrGrGrArGrUrUr UrGrArGrArArArCrCrUr GrArArArArArGrGrUrGr ArGrUrGrCrArArArArUr ArArGrGrUrUrUrArAr CrCrGrArArArUrUrGr UrUrUrArCrCrUrGrCr ArUrUrGrUrGrCrArGr UrArUrArArGrArArAr GrArCrCrGrCrGrArGr GrUrCrU*mU*mU*mU sgRN A MG2 3 -1 directed at HAO1 human in 273 MG23-1 hHAO1sgRNAC2 artificial nucleotide mC*mA*mA*rCrArUrGr CrUrArArArUrCrArGr UrArCrUrUrCrGrUrUr UrGrArGrArArCrCrUr GrArArArGrGrUrGr ArGrUrGrCrArArArUr ArArGrGrUrUrUrArAr CrCrGrArArArUrUrGr UrUrUrArCrCrUrGrCr ArUrUrGrUrGrCrArGr UrArUrArArGrArArAr GrArCrCrGrCrGrArGr GrUrCrU*mU*mU*mU sgRN A MG2 3 -1 directed at HAO1 human in 274 MG23-1 hHAO1sgRNAD2 artificial nucleotide mU*mA*mU*rGrArCrUr ArUrUrArCrArGrGrUr CrUrGrGrGrGrGrUrUr UrGrArGrArArCrCrUrGrArArArArArGrGrUrGr ArGrUrGrCrArArArUr ArArGrGrUrUrUrArAr CrCrGrArArArUrUrGr UrUrUrArCrCrUrGrCr ArUrUrGrUrGrCrArGr UrArUrArArGrArArAr Petition 870250090553, dated 03 / 10 / 2025, pp. 242 / 262 239 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence GrArCrCrGrCrGrArGr GrUrCrU*mU*mU*mU DNA sequence of the target site of HAO1 Human 275 MG23-1 hHAO1Target Site-A4 artificial nucleotide AGTTACCTGGAAAGCTAA GCCC DNA sequence of the target site of HAO1 Human 276 MG23-1 hHAO1Target Site-H8 artificial nucleotide TCTTTTCACTTGGTTAGG GGGA DNA sequence of the target site of HAO1 Human 277 MG23-1 hHAO1Target Site-C2 artificial nucleotide CAACATGCTAAATCAGTA CTTC Sequence of 278 MG23-1 hHAO1- artificial nucleotide TATGACTATTACAGGTCT GGGG Petition 870250090553, dated 03 / 10 / 2025, pp. 243 / 262 240 / 251 Cat. SEQ ID NO: Description Type Organism Other Information DNA sequence of the target site of HAO1 Human Target Site-D2 sgRNA A MG21-1 directed to human TTR 279 MG23-1 hTTRsgRNAF1 artificial nucleotide mC*mA*mG*rCrCrUrAr GrCrUrCrArGrGrArGr ArArGrUrGrArGrUrUr GrUrArGrUrUrCrCrCr CrUrUrUrUrGrArArArArArArArGrUrGrUrGrUrGr UrUrArCrUrGrCrArArAr UrArArGrGrUrArArArArCrCrArCrGrAr ArGrCrUrCrUrGrCrCr CrUrArArCrUrGrCrCr UrUrArGrCrArGrUrUr ArGrGrGrCrArUrC*mU *mU*mU sgRN A MG21 -1 targeting human TTR in 280 MG23-1 hTTRsgRNAA4 artificial nucleotide mU*mA*mC*rCrArGrUr CrCrArGrCrArArGrGr CrArGrArGrGrGrUrUr GrUrArGrUrUrCrCrCr CrUrUrUrUrGrArArAr ArArArArGrUrGrUrGr UrUrArCrUrGrCrArAr UrArArGrGrUrArArAr ArCrArCrCrArCrGrAr ArGrCrUrCrUrGrCrCr CrUrArArCrUrGrCrCr UrUrArGrCrArGrUrUr ArGrGrGrCrArUrC*mU *mU*mU sgRN A MG21 -1 dire 281 MG23-1 hTTRsgRNAB4 artificial nucleotide mC*mA*mA*rGrGrCrAr GrArGrGrArGrGrArGr CrArGrArCrGrGrUrUr GrUrArGrUrUrCrCrCr CrUrUrUrUrGrArArAr Petition 870250090553, dated 03 / 10 / 2025, pp. 244 / 262 241 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence directed to human TTR ArArArArGrUrGrUrGr UrUrArCrUrGrCrArAr UrArArGrGrUrArArArArCrArCrCrGrAr ArGrCrUrCrUrGrCrCr CrUrArArCrUrGrCrCr UrUrArGrCrArGrUrUr ArGrGrGrCrArUrC*mU *mU*mU sgRNA A MG21-1 directed to human TTR 282 MG23-1 hTTRsgRNAG1 artificial nucleotide mG*mU*mG*rArGrUrAr UrArArArArGrCrCrCr CrArGrGrCrUrGrUrUr GrUrArGrUrUrCrCrCr CrUrUrUrUrGrArArAr ArArArArGrUrGrUrGr UrUrArCrUrGrCrArAr UrArArGrGrUrArArAr ArCrArCrCrArCrGrAr ArGrCrUrCrUrGrCrCr CrUrArArCrUrGrCrCr UrUrArGrCrArGrUrUr ArGrGrGrCrArUrC*mU *mU*mU sgRN A MG21 -1 targeting human TTR in 283 MG23-1 hTTRsgRNAF3 artificial nucleotide mC*mA*mC*rUrCrArCr CrGrUrArGrGrGrCrCr ArGrCrCrUrCrGrUrUr GrUrArGrUrUrCrCrCr CrUrUrUrUrGrArArAr ArArArArGrUrGrUrGr UrUrArCrUrGrCrArAr UrArArGrGrUrArArAr ArCrArCrCrArCrGrAr ArGrCrUrCrUrGrCrCr CrUrArArCrUrGrCrCr UrUrArGrCrArGrUrUr ArGrGrGrCrArUrC*mU *mU*mU sgRN A MG21 -1 dire 284 MG23-1 hTTRsgRNAH1 nucleotideartificial mC*mA*mG*rArCrGrAr UrGrArGrArArGrCrCr ArUrCrCrUrGrGrUrUr GrUrArGrUrUrCrCrCr CrUrUrUrUrGrArArAr Petition 870250090553, dated 03 / 10 / 2025, pages 245 / 262 242 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence directed to human TTR ArArArArGrUrGrUrGr UrUrArCrUrGrCrArAr UrArArGrGrUrArArArArCrArCrGrAr ArGrCrUrCrUrGrCrCr CrUrArArCrUrGrCrCr UrUrArGrCrArGrUrUr ArGrGrGrCrArUrC*mU *mU*mU sgRNA A MG21-1 directed to human TTR 285 MG23-1 hTTRsgRNAC4 artificial nucleotide mC*mA*mG*rArCrGrAr UrGrArGrArArGrCrCr ArUrCrCrUrGrGrUrUr GrUrArGrUrUrCrCrCr CrUrUrUrUrGrArArAr ArArArArGrUrGrUrGr UrUrArCrUrGrCrArAr UrArArGrGrUrArArAr ArCrArCrCrArCrGrAr ArGrCrUrCrUrGrCrCr CrUrArArCrUrGrCrCr UrUrArGrCrArGrUrUr ArGrGrGrCrArUrC*mU *mU*mU sgRN A MG21 -1 targeting human TTR in 286 MG23-1 hTTRsgRNAF5 artificial nucleotide mA*mG*mC*rUrGrCrAr UrGrGrGrCrUrCrArCr ArArCrUrGrArGrUrUr GrUrArGrUrUrCrCrCr CrUrUrUrUrGrArArAr ArArArArGrUrGrUrGr UrUrArCrUrGrCrArAr UrArArGrGrUrArArAr ArCrArCrCrArCrGrAr ArGrCrUrCrUrGrCrCr CrUrArArCrUrGrCrCr UrUrArGrCrArGrUrUr ArGrGrGrCrArUrC*mU *mU*mU sgRN A MG21 -1 dire 287 MG23-1 hTTRsgRNAD4 nucleotideartificial mG*mU*mC*rUrUrCrUr CrUrArCrArCrCrCrAr GrGrGrCrArCrGrUrUr GrUrArGrUrUrCrCrCr CrUrUrUrUrGrArArAr Petition 870250090553, dated 03 / 10 / 2025, pages 246 / 262 243 / 251 Cat. SEQ ID NO: Description Type Organism Other Information Sequence directed to human TTR ArArArArGrUrGrUrGr UrUrArCrUrGrCrArAr UrArArGrGrUrArArArArCrArCrGrAr ArGrCrUrCrUrGrCrCr CrUrArArCrUrGrCrCr UrUrArGrCrArGrUrUr ArGrGrGrCrArUrC*mU *mU*mU sgRNA A MG21-1 directed to human TTR 288 MG23-1 hTTRsgRNAA3 artificial nucleotide mU*mU*mA*rGrArGrCr ArUrCrGrGrArArCrAr UrUrCrGrUrUrGrUrUr GrUrArGrUrUrCrCrCr CrUrUrUrUrGrArArAr ArArArArGrUrGrUrGr UrUrArCrUrGrCrArAr UrArArGrGrUrArArAr ArCrArCrCrArCrGrAr ArGrCrUrCrUrGrCrCr CrUrArArCrUrGrCrCr UrUrArGrCrArGrUrUr ArGrGrGrCrArUrC*mU *mU*mU sgRN A MG21 -1 targeting human TTR in 289 MG23-1 hTTRsgRNAE1 artificial nucleotide mG*mC*mA*rGrGrGrAr UrArArGrCrArGrCrCr UrArGrCrUrCrGrUrUr GrUrArGrUrUrCrCrCr CrUrUrUrUrGrArArAr ArArArArGrUrGrUrGr UrUrArCrUrGrCrArAr UrArArGrGrUrArArAr ArCrArCrCrArCrGrAr ArGrCrUrCrUrGrCrCr CrUrArArCrUrGrCrCr UrUrArGrCrArGrUrUr ArGrGrGrCrArUrC*mU *mU*mU sgRN A MG21 -1 dire 290 MG23-1 hTTRsgRNAD1 nucleotideartifi...

Claims

1. Modified nuclease system, characterized in that it comprises: a) an endonuclease comprising a sequence having at least 80% sequence identity with respect to any of the following SEQ ID NOs: 303, 304, 139 to 146, 1 to 5, 6, 7 to 11, 12 to 14, 105 to 109, 110 to 116 and 117 to 138; and b) a modified guide polynucleotide configured to form a complex with the endonuclease and hybridize with a target nucleic acid sequence.

2. Modified nuclease system according to claim 1, characterized in that the endonuclease comprises a sequence having at least 90% or 100% sequence identity with respect to any of the following SEQ ID NOs: 303, 304, 139 to 146, 1 to 5, 6, 7 to 11, 12 to 14, 105 to 109, 110 to 116 and 117 to 138.

3. Modified nuclease system, according to claim 1 or 2, characterized in that the modified guide polynucleotide comprises a crRNA and a tracrRNA; wherein the tracrRNA comprises a sequence having at least 90% or 100% sequence identity with respect to any of the SEQ ID NOs: 215 to 222, 52, 147 to 151, 157 to 163 and 171 to 192.

4. Modified nuclease system, characterized in that it comprises: a) an endonuclease comprising a sequence having at least 80% sequence identity with respect to any of the SEQ ID NOs: 303 and 139 to 146; and b) a modified guide polynucleotide configured to form a complex with the endonuclease and hybridize with a target nucleic acid sequence, the modified guide polynucleotide comprising a sequence having at least 80% sequence identity with respect to any of the SEQ ID NOs: 215 to 222.

5. Modified nuclease system, characterized in that it comprises: (i) a) an endonuclease comprising a sequence having at least 80% sequence identity with respect to any of the SEQ ID NOs: 7 to 11; and b) a modified guide polynucleotide configured to form a complex with the endonuclease and hybridize with a target nucleic acid sequence, the modified guide polynucleotide comprising a sequence having at least 80% sequence identity with respect to SEQ ID NO: 52; (ii) a) an endonuclease comprising a sequence having at least 80% sequence identity with respect to any of the SEQ ID NOs: 105 to 109; (b) a modified guide polynucleotide configured to form a complex with the endonuclease and hybridize with a target nucleic acid sequence, the modified guide polynucleotide comprising a sequence having at least 80% sequence identity with respect to any of the SEQ ID Nos: 147 to 151;(iii) a) an endonuclease comprising a sequence having at least 80% sequence identity with respect to any of the SEQ ID NOs: 110 to 116; and b) a modified guide polynucleotide configured to form a complex with the endonuclease and hybridize with a target nucleic acid sequence, the modified guide polynucleotide comprising a sequence having at least 80% sequence identity with respect to any of the SEQ ID NOs: 157 to 163; or (iv) a) an endonuclease comprising a sequence having at least 80% sequence identity with respect to any of the SEQ ID NOs: 117 to 138; (b) a modified guide polynucleotide configured to form a complex with the endonuclease and hybridize with a target nucleic acid sequence, the modified guide polynucleotide comprising a sequence having at least 80% sequence identity with respect to any of the SEQ ID Nos: 171 to 192; 6. Modified nuclease system, according to any one of claims 1 to 5, characterized in that: a) the modified guide polynucleotide is a single guide nucleic acid or a double guide nucleic acid; b) the modified guide polynucleotide is an RNA endonuclease; c) the non-guide endonuclease is a Cas9 endonuclease, a Cas14 endonuclease, a Cas12a endonuclease, a Cas12b endonuclease, a Cas12c endonuclease, a Cas12d endonuclease, a Cas12e endonuclease, a Cas13a endonuclease, a Cas13b endonuclease, a Cas13c endonuclease or a Cas13d endonuclease; d) the endonuclease has less than 80% identity with respect to a Cas9 endonuclease; and / or e) the endonuclease binds non-covalently to the modified guide polynucleotide or the endonuclease is covalently bound to the modified guide polynucleotide.

7. Modified nuclease system, according to claim 4 or 5, characterized in that the endonuclease fuses to the modified guide polynucleotide.

8. A method for modifying a target nucleic acid sequence, characterized in that it comprises bringing the target nucleic acid sequence into contact with the modified nuclease system, as defined in any one of claims 1 to 7.

9. A method according to claim 8, characterized in that the modification of the target nucleic acid sequence comprises ligating, cutting, or cleaving the target nucleic acid sequence.

10. Method according to claim 8 or 9, characterized in that the target nucleic acid sequence comprises genomic DNA, viral DNA, viral RNA or bacterial DNA.

11. Method according to claim 8 or 10, characterized in that the modification is in vitro, in vivo or ex vivo.

12. Method, according to any one of claims 8 to 11, characterized in that: a) the modified guide polynucleotide is encoded by a sequence having any one of the SEQ ID NOs: 251 to 260, 271 to 274 and 279 to 290; and / or b) the target nucleic acid sequence comprises a sequence having any one of the SEQ ID NOs: 261 to 270, 275 to 278 and 291 to 302.

13. Use of the modified nuclease system, as defined in any one of claims 1 to 7, characterized in that it is for modifying a target nucleic acid sequence in a mammalian cell, the use comprising placing the mammalian cell in contact with the aforementioned system.

14. Use according to claim 13, characterized in that it further comprises selecting cells comprising modification.

15. HAO1 modification method, characterized in that it comprises bringing HAO1 into contact with a modified nuclease system comprising: a) an endonuclease comprising a sequence having at least 80% sequence identity with respect to any of the SEQ ID NOs: 303 and 139 to 146; and b) a modified guide polynucleotide configured to form a complex with the endonuclease and hybridize with a target nucleic acid sequence, the modified guide polynucleotide comprising a sequence having at least 80% sequence identity with any of the SEQ ID NOs: 215 to 222.

16. Method according to claim 15, characterized in that: a) the modified guide polynucleotide is encoded by a sequence having any of the SEQ ID NOs: 251 to 260; and / or b) the target nucleic acid sequence comprises a sequence having any of the SEQ ID NOs: 261 to 270.

17. HAO1 modification method, characterized in that it comprises bringing HAO1 into contact with a modified nuclease system comprising: a) an endonuclease comprising a sequence having at least 80% sequence identity with respect to SEQ ID NO: 304; and b) a modified guide polynucleotide configured to form a complex with the endonuclease and hybridize with a target nucleic acid sequence.

18. Method according to claim 17, characterized in that: a) the modified guide polynucleotide is encoded by a sequence having any of the SEQ ID NOs: 271-274; and / or b) the target nucleic acid sequence comprises a sequence having any of the SEQ ID NOs: 275-278.

19. TTR modification method characterized in that it comprises bringing TTR into contact with a modified nuclease system comprising: a) an endonuclease comprising a sequence having at least 80% sequence identity with respect to any of the SEQ ID NOs: 303 and 139 to 146; and b) a modified guide polynucleotide configured to form a complex with the endonuclease and hybridize with a target nucleic acid sequence, the modified guide polynucleotide comprising a sequence having at least 80% sequence identity with respect to any of the SEQ ID NOs: 215 to 222.

20. Method according to claim 19, characterized in that: a) the modified guide polynucleotide is encoded by a sequence having any of the SEQ ID NOs: 279 to 290; and / or b) the target nucleic acid sequence comprises a sequence having any of the SEQ ID NOs: 291 to 302.

21. Cell, characterized in that it comprises the modified nuclease system, as defined in any one of claims 1 to 7, as per Petition 870250090557, dated 10 / 03 / 2025, pp. 23 / 27 7 / 7; optionally wherein the cell is: a) a eukaryotic cell; b) a mammalian cell, optionally wherein the mammalian cell is an A549, a HEK-293, a HEK-293T, a BHK, a CHO, a HeLa, an MRC5, a Cos-1, a Cos-7, a Vero, a BSC 1, a BSC 40, a BMT 10, a WI38, a Saos, a C2C12, an aHT1080, a HepG2, a Huh7, a K562, an L cell, a primary cell or a derivative thereof; c) an immortalized cell; d) an insect cell, optionally where the insect cell is an sf9 or a derivative thereof; e) a yeast cell; f) a plant cell; g) a fungal cell; h) a prokaryotic cell; i) a modified cell; j) a stable cell.

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