Modified t cell receptors for the prevention and treatment of viral infections and cancer

Abstract

Abstract Modified T cell receptors, cells comprising the modified T cell receptors, nucleic acids encoding the modified T cell receptors, and methods for using the modified T cell receptors are contemplated. Modified T cell receptor comprising two peptide chains are disclosed herein. The two peptide chains may be the same or different, and each peptide chain comprises an extracellular domain comprising a variable region, a constant region, and a connecting peptide, a transmembrane domain, and an intracellular domain comprising a CD28 region and a CD3 ζ ITAM region. Nucleic acids encoding the modified T cell receptors, and vectors comprising the nucleic acids are also disclosed. Additionally, a method for treating cancer and / or a viral infection is disclosed comprising administering a cell comprising the modified T cell receptor. Abstract

Description

CROSS-REFERENCE TO RELATED APPLICATIONS 5

[0001] This application claims the benefit of U.S. Provisional Application No. 63 / 227,195 filed July 29, 2021. The entire disclosure of the above application is incorporated herein by reference. REFERENCE TO A SEQUENCE LISTING

[0002] The present disclosure contains references to amino acid sequences and nucleic acid 10 sequences which have been submitted concurrently herewith as the sequence listing xml file entitled “17768IB-01-WO-POA_seq_listing.xml,” file size 107 KiloBytes (KB), created on July 25, 2022. The aforementioned sequence listing is hereby incorporated by reference in its entirety pursuant to 37 C.F.R. § 1.52(e)(5). FIELD OF THE INVENTION 15

[0003] The present disclosure relates to modified T cell receptors (TCRs) that can be administered to subjects for the prevention and / or treatment of viral infections and / or cancer. BACKGROUND

[0004] The background description includes information that may be useful in understanding the compositions and methods described herein. It is not an admission that any of the information 20 provided herein is prior art or relevant to the compositions and methods, or that any publication specifically or implicitly referenced is prior art.

[0005] TCRs are transmembrane proteins located on the surface of T cells which recognize antigens presented by major histocompatibility complex (MHC) I or II molecules from antigen presenting cells (APCs). Signaling through the T cell receptor with proper co-stimulation initiates 25 a signaling pathway that activates the T cell to respond to an antigen (e.g. through the release of pro-inflammatory cytokines by helper CD4+ T cells or initiation of cell lysis by cytotoxic CD8+ T cells).

[0006] Cancers and viruses can escape T cell-mediated immune responses by mitigating TCR signaling, thereby downregulating the T cell response. Modifying a TCR to promote a T cell 30 response can improve the host’s immune response to a cancer or a viral infection. This data, for application number 2022317127, is current as of 2025-04-28 21:51 AEST 2025202995   29 Apr 2025

[0007] T-Cell Receptor (TCR) molecules function in cellular contexts as dimers. Transgenically modifying T cell TCRs requires adding genes for each monomeric unit in the dimer. Because, however, T cells already contain natural TCRs, it is possible for the transgenic TCR monomers to heterodimerize with the natural TCRs. These hybrid TCRs can give rise to off-target effects in the 5 transgenic T cells, wherein the effects of transgenic and / or endogenous TCR are reduced or eliminated by cross-binding of their respective peptide chains (Govers & al. (2010) Trends Mol. Med. 16(2):77-87). Thus, there remains a need to provide modified T cell receptors to enhance an immune response against specific antigens (e.g., antigens from cancer cells or viruses) for the treatment of cancer and / or viral infections. 10 SUMMARY

[0008] Disclosed herein are modified TCRs that can be used to treat and / or prevent viral infections and / or cancer. The modified TCRs are heterodimers comprising two different peptide chains. The individual peptide chains of the modified TCRs each comprise an extracellular domain, a transmembrane domain, and an intracellular domain. The extracellular domain comprises a 15 variable region, a constant region, and a connecting peptide, wherein the variable region and the constant region are attached via a linker. The connecting peptide is located between the constant region and the transmembrane domain. In some embodiments, the intracellular domain comprises a CD28 region and a CD3(^ IT AM region.

[0009] Also disclosed are methods for expressing a functional modified TCR into a T cell, 20 wherein the peptide fragments of the modified TCR self-assemble on the cell surface with each other and not with endogenous TCR peptides also expressed on the T cell surface. The modified TCR can be genetically engineered to express a variable region comprising a and P chains with specificity for an HLA presented peptide. The modified TCR can be genetically engineered to express a variable region comprising an Ig variable domain with specificity for a tumor specific 25 antigen.

[0010] Also disclosed herein are cells comprising the modified TCR.

[0011] Also disclosed herein are nucleic acids encoding the modified TCR and vectors comprising the nucleic acid encoding the modified TCR

[0012] Also disclosed herein are methods for the prevention and / or treatment of cancer or a viral 30 infection in a patient in need thereof, the method comprising administering a therapeutically effective amount a pharmaceutical composition comprising a the modified TCR, a nucleic acid encoding the modified TCR, or a cell comprising the modified TCR to the patient. 2025202995   29 Apr 2025

[0013] Various objects, features, aspects, and advantages will become more apparent from the following detailed description of preferred embodiments, along with the accompanying drawings. BRIEF DESCRIPTION OF THE DRAWINGS

[0014] FIG. 1 depicts an embodiment of a modified TCR of the present disclosure comprising a 5 heterodimer of peptide chains P-NR-025 and P-NR-026.

[0015] FIG. 2 depicts another embodiment of a modified TCR of the present disclosure comprising a heterodimer of peptide chains P-NR-027 and P-NR-028.

[0016] FIGs. 3A-3D depict plasmid constructs encoding particular peptide chains of the modified TCRs of the present disclosure. FIG. 3A depicts a plasmid encoding the peptide chain p-NR-025. 10 FIG. 3B depicts a plasmid encoding the peptide chain p-NR-026. FIG. 3C depicts a plasmid encoding the peptide chain p-NR-027. FIG. 3D depicts a plasmid encoding the peptide chain p-NR-028.

[0017] FIGs. 4A-4E show the results of a killing assay of activated natural killer (aNK) cells transfected with plasmid constructs encoding peptide chains of the modified TCRs of the present 15 disclosure. FIGs. 4A and 4B show the target cell lysis by aNK cells transfected with the modified TCR P-NR-025 + P-NR-026 and P-NR-027 + P-NR-028, respectively. FIGs. 4C-4E show the target cell lysis of positive and negative control aNK cells.

[0018] FIG. 5 depicts the chimeric TCR expression in aNK (NK92) cells transfected with plasmid constructs encoding peptide chains of chimeric TCR P-NR-025 + P-NR-026, P-NR-025 + 20  PWH295, PWH305 + PWH 308, and PWH3O3 + PWH3O8.

[0019] FIG. 6 shows the results of a killing assay in aNKs expressing wild type and chimeric TCRs shown in FIG. 5.

[0020] FIG. 7 depicts chimeric TCR expression in aNKs transfected with plasmid constructs encoding peptide chains of chimeric TCR PWH305 + PWH308 and PWH3O3 + PWH3O8. 25

[0021] FIG. 8 shows the results of a killing assay in aNKs expressing wild type and chimeric TCRs shown in FIG. 7. DETAILED DESCRIPTION I. Definitions

[0022] The following definitions refer to the various terms used above and throughout the 30 disclosure. 2025202995   29 Apr 2025

[0023] “T cell receptor” or “TCR” refers to a dimeric polypeptide that is typically found on the surface of T cells. Each peptide chain of a TCR generally comprises an extracellular domain comprising a variable region and a constant region, a transmembrane domain, and an intracellular domain. The variable region is the portion of the TCR that interacts with the antigen presented by 5 the MHC. The constant region is the area in each of the two peptides wherein the two peptide chains are covalently linked by a disulfide bond. The intracellular domain generally comprises a CD3^, which comprises one or more immunoreceptor tyrosine-based activation motifs (ITAMs). The ITAM mediates the binding of the variable region to the appropriate intracellular signaling pathways. 10

[0024] “Encoding”—when used in reference to a nucleic acid—conveys that when transcription is initiated from the nucleic acid in a cell, the transcript produced would be translated into a given protein. That is to say, a nucleic acid “encodes” a peptide when the codon triplets of tRNA would produce the polypeptide from the nucleic acid according to the ordinary workings of transcription and translation in the cell. 15

[0025] “Effective amount” or “therapeutically effective amount” refers to the amount and / or dosage, and / or dosage regime of one or more agent(s) necessary to bring about the desired result e.g., an amount sufficient to prevent a viral infection in a subject, an amount sufficient to reduce the occurrence of a viral infection in a subject, and / or an amount sufficient to treat a viral infection in a subject. Alternatively, the effective amount or therapeutically effective amount refers to the 20 amount and / or dosage and / or dosage regime sufficient to reduce the occurrence of a cancer in a subject, and / or an amount sufficient to treat a cancer in a subject.

[0026] “Cancer” refers to one or more conditions comprising the development of tumors, neoplasms, or otherwise unwanted, abnormal, and / or uncontrolled cellular growth in a patient’s body, tissue, or organ. In certain embodiments, the cancer is selected from the group consisting of 25 bladder cancer, bone cancer, brain cancer (including medulloblastoma, meningioma, neuroblastoma), breast cancer, cancer of the central nervous system, cervical cancer, colon cancer, colorectal cancer, esophageal cancer, eye cancer, gall bladder cancer, head and neck cancer, gastric cancer, HIV / AIDS related cancer, kidney cancer, leukemia, (including acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), B cell leukemia (BCL), chronic lymphocytic 30 cancer (CLL), chronic myeloid leukemia (CML), and chronic T cell lymphocytic leukemia (CTLL)), liver cancer, lung cancer (including non-small cell and small cell), lymphoma (including non-Hodgkin lymphoma and Hodgkin lymphoma), melanoma, multiple myeloma, nasopharyngeal cancer, oral cancer (including cancer of the mouth, tongue, salivary glands, or 2025202995   29 Apr 2025 gums), neuroendocrine cancer, ovarian cancer, pancreatic cancer, prostate cancer, retinoblastoma, sarcoma, skin cancer, stomach cancer, testicular cancer, thyroid cancer, uterine cancer, and vaginal cancer. In a particular embodiment, the cancer is bladder cancer, breast cancer, colon cancer, or pancreatic cancer. 5

[0027] “Identical” or percent “identity,” in the context of two or more nucleic acids or polypeptide sequences, refer to two or more sequences or subsequences that are the same or have a specified percentage of amino acid residues or nucleotides that are the same, when compared and aligned for maximum correspondence over a comparison window. The degree of amino acid or nucleic acid sequence identity for purposes of the present disclosure is determined using the BLAST 10 algorithm, described in Altschul et al. (199) J. Mol. Biol. 215:403-10, which is publicly available through software provided by the National Center for Biotechnology Information (at the web address www.ncbi.nlm.nih.gov). This algorithm identifies high scoring sequence pairs (HSPS) by identifying short words of length W in the query sequence, which either match or satisfy some positive-valued threshold score T when aligned with a word of the same length in a database 15 sequence. T is referred to as the neighborhood word score threshold (Altschul etal., supra.). Initial neighborhood word hits act as seeds for initiating searches to find longer HSPs containing them. The word hits are then extended in both directions along each sequence for as far as the cumulative alignment score can be increased. Cumulative scores are calculated for nucleotides sequences using the parameters M (reward score for a pair of matching residues; always >0) and N (penalty 20 score for mismatching residues; always <0). For amino acid sequences, a scoring matrix is used to calculate the cumulative score. Extension of the word hits in each direction are halted when: the cumulative alignment score falls off by the quantity X from its maximum achieved value; the cumulative score goes to zero or below due to the accumulation of one or more negative-scoring residue alignments; or the end of either sequence is reached. For determining the percent identity 25 of an amino acid sequence or nucleic acid sequence, the default parameters of the BLAST programs can be used. For analysis of amino acid sequences, the BLASTP defaults are: word length (W), 3; expectation (E), 10; and the BLOSUM62 scoring matrix. For analysis of nucleic acid sequences, the BLASTN program defaults are word length (W), 11; expectation (E), 10; M=5; N=-4; and a comparison of both strands. The TBLASTN program (using a protein sequence 30 to query nucleotide sequence databases) uses as defaults a word length (W) of 3, an expectation (E) of 10, and a BLOSUM 62 scoring matrix, (see Henikoff & Henikoff (1989) Proc. Natl. Acad. Sci. USA 89:10915).

[0028] In addition to calculating percent sequence identity, the BLAST algorithm also performs a statistical analysis of the similarity between two sequences (see, e.g., Karlin & Altschul (1993) 2025202995   29 Apr 2025 Proc. Nat'l. Acad. Sci. USA 90:5873-87). The smallest sum probability (P(N)), provides an indication of the probability by which a match between two nucleotide or amino acid sequences would occur by chance. For example, a nucleic acid is considered similar to a reference sequence if the smallest sum probability in a comparison of the test nucleic acid to the reference nucleic 5 acid is less than about 0.01.

[0029] “Viral infection” refers to a condition in which a virus has entered a host, such as a patient, and replicates. A viral infection does not require that the host presents symptoms of the viral infection. The term “virus” is not particularly limited and refers to both DNA and RNA viruses. The DNA virus may be a single- or double-stranded virus and may belong to any family of DNA 10 viruses, including, but not limited to, herpesviridae, adenoviridae, polyomavididae, and poxviridae. Particular embodiments of DNA viruses include the human herpesvirus and varicella zoster virus. The RNA virus may also be single- or double-stranded and may belong to any family of RNA viruses, including, but not limited to, reoviridae, coronaviridae, picornaviridae, flaviviridae, hepeviridae, togaviridae, filoviridae, paramyxoviridae, pneumoviridae, 15 rhabdoviridae, hantaviridae, and orthomyxoviridae. Particular embodiments of RNA viruses include rotavirus, coronavirus, SARS virus, poliovirus, rhinovirus, hepatitis A virus, yellow fever virus, west nile virus, hepatitis C virus, dengue fever virus, zika virus, rubella virus, sindbis virus, Chikungunya virus, Ebola virus, Marburg virus, measles virus, mumps virus, respiratory syncytial virus, rabies virus, influenza virus A, influenza virus B, influenza virus C, and influenza virus D. 20 In some embodiments, the virus is human immunodeficiency virus.

[0030] “Subject,” “individual,” and “patient” interchangeably refer to a mammal, preferably a human or a non-human primate, but also domesticated mammals (e.g., canine or feline), laboratory mammals (e.g., mouse, rat, rabbit, hamster, guinea pig), and agricultural mammals (e.g., equine, bovine, porcine, ovine). In certain embodiments, the subject can be human (e.g., adult male, adult 25 female, adolescent male, adolescent female, male child, female child) under the care of a physician or other health worker. In certain embodiments the subject may not be under the care of a physician or other health worker.

[0031] “Treat” and “treatment” each refer to a method for reducing, inhibiting, or otherwise ameliorating an infection by administering a therapeutic to a subject in need of treatment. In some 30 embodiments, the subject in need of treatment may include a subject having, diagnosed as having, or suspected to have an infection, such as a viral infection. In a particular embodiment, treat or treatment includes administering a therapeutic agent to a subject having, diagnosed as having, or suspected of having a disease, disorder, or condition (e.g., cancer or a viral infection). In some 2025202995   29 Apr 2025 embodiments, the subject may be asymptomatic. Treatment includes administration of a modified TCR, a cell comprising the modified TCR, a nucleic acid encoding the modified TCR, and / or a vector comprising the nucleic acid encoding the modified TCR.

[0032] ‘‘Concomitant” or “concomitantly” includes administering an agent (e.g., a modified TCR, 5 a cell comprising the modified TCR, and / or nucleic acid encoding the modified TCR) in the presence of an additional agent. Concomitant administration in a therapeutic treatment method includes methods in which a first, second, third, or additional agents are co-administered. Concomitant administration also includes methods in which the first or additional agents are administered in the presence of a second or additional agents, wherein the second or additional 10 agents, for example, may have been previously administered. A concomitant therapeutic treatment method may be executed step-wise by different actors. For example, one actor may administer to a subject a first agent and a second actor may administer to the subject a second agent, and the administering steps may be executed at the same time, or nearly the same time. The actor and the subject may be the same entity (e.g., human). Thus, the term embraces both simultaneous 15 administration and substantially simultaneous administration, i.e., at about the same time. II. Modified T cell Receptor

[0033] The modified TCR of the present invention relates to a dimeric polypeptide based on a TCR structure. In particular, the modified TCR comprises two peptide chains, each of which comprise an extracellular domain (comprising a variable region, a constant region, and a 20 connecting peptide), a transmembrane domain, and an intracellular domain. In a specific embodiment, the variable region and constant region are attached via a linker. In another specific embodiment, the connecting peptide is located between the constant region and the transmembrane domain. In a further specific embodiment, the two peptide chains are connected to each other by a disulfide bond between the connecting peptides of each peptide chain. 25

[0034] The extracellular domain comprises a variable region, a constant region, and a connecting peptide. The exact sequence of the variable region is not particularly limited except that it is capable of recognizing an antigen presented on an MHC molecule. By convention the variable region on one of the modified TCR peptide chains may be called “Va” and the variable region on the other peptide chain may be termed “Vp.” In some embodiments, the variable regions of both 30 peptide chains are the same. In alternative embodiments, the variable regions on each of the peptide chains are different. In a particular embodiment, the Va comprises the sequence of SEQ ID NO: 15 (Va-1) or SEQ ID NO: 30 (Va-2). In another embodiment, the VP comprises the sequence of SEQ ID NO: 16 (VP-1) or SEQ ID NO: 31 (VP-2). Alternatively, the variable region 2025202995   29 Apr 2025 comprises a sequence having at least 70% sequence identity (i.e., at least 75% sequence identity, at least 80% sequence identity, at least 85% sequence identity, at least 90% sequence identity, at least 95% sequence identity, at least 96% sequence identity, at least 97% sequence identity, at least 98% sequence identity, or at least 99% sequence identity) to SEQ ID NO: 15, SEQ ID NO: 5   16, SEQ ID NO: 30, or SEQ ID NO: 31. In certain embodiments, the variable region comprises a sequence having at least 70% sequence identity (i.e., at least 75% sequence identity, at least 80% sequence identity, at least 85% sequence identity, at least 90% sequence identity, at least 95% sequence identity, at least 96% sequence identity, at least 97% sequence identity, at least 98% sequence identity, or at least 99% sequence identity) to SEQ ID NO: 15 or SEQ ID NO: 30, but 10   100% identity to any or all of three complementarity determining regions (CDRs) of SEQ ID NO: 15 or SEQ ID NO: 30. In certain embodiments, the variable region comprises a sequence having at least 70% sequence identity (i.e., at least 75% sequence identity, at least 80% sequence identity, at least 85% sequence identity, at least 90% sequence identity, at least 95% sequence identity, at least 96% sequence identity, at least 97% sequence identity, at least 98% sequence identity, or at 15 least 99% sequence identity) to SEQ ID NO: 16 or SEQ ID NO: 31, but 100% identity to any or all of three complementarity determining regions (CDRs) of SEQ ID NO: 16 or SEQ ID NO: 31.

[0035] The constant region represents a peptide sequence between the variable region and the connecting peptide. In a specific embodiment, the constant region comprises an immunoglobulin (Ig) domain or a coiled-coil domain. In some embodiments, the constant regions of both peptide 20 chains are the same. In alternative embodiments, the constant regions of each of the peptide chains is different.

[0036] In a particular embodiment the constant region is an Ig domain. The Ig domain is not particularly limited and may include IgA, IgD, IgE, IgG, and IgM. The constant region may comprise Ig-CK, IgG-CH-1, or IgM-CH-1. In a specific embodiment the Ig-CK comprises the 25 sequence of SEQ ID NO: 17. In another embodiment, the IgG-CH-1 comprises the sequence of SEQ ID NO: 18 (IgG-CH-la) or SEQ ID NO: 32 (IgG-CH-lb). In yet another embodiment, the IgM-CH-1 comprises the sequence of SEQ ID NO: 33. In a particular embodiment, the constant region of one peptide chain of the modified TCR comprises the sequence of Ig-CK and the constant region of the other peptide chain of the modified TCR comprises the sequence of Ig-CH-1, such 30 as IgG-CH-la, IgG-CH-lb, and IgM-CH-1. Alternatively, the constant region comprises a sequence having at least 70% sequence identity (i.e., at least 75% sequence identity, at least 80% sequence identity, at least 85% sequence identity, at least 90% sequence identity, at least 95% sequence identity, at least 96% sequence identity, at least 97% sequence identity, at least 98% sequence identity, or at least 99% sequence identity) to SEQ ID NO: 17, SEQ ID NO: 18, SEQ 2025202995   29 Apr 2025 ID NO: 32, or SEQ ID NO: 33.

[0037] In an alternative particular embodiment, the constant region is a coiled-coil domain such as a WinZip domain. WinZip domains have been described. See, for example, US 6,897,017, the which is incorporated by reference herein in its entirety. In a specific embodiment, the WinZip 5 domain is selected from the group consisting of WinZip-A2 (corresponding to SEQ ID NO: 20) and WinZip-Bl (corresponding to SEQ ID NO: 19). In a particular embodiment, the constant region of one peptide of the modified TCR comprises WiriZip-A2 and the constant region of the other peptide of the modified TCR comprises WinZip-Bl.

[0038] The linker that links the variable region and the constant region may be a flexible linker. 10 In a particular embodiment, the linker comprises the amino acid sequence of GGSGG (SEQ ID NO: 2).

[0039] The connecting peptide conjoins the constant region to the transmembrane domain. In some embodiments, the connecting peptide comprises an amino acid sequence selected from the group consisting of GSG or GGCGG (SEQ ID NO: 1). 15

[0040] The extracellular region (comprising a variable region, a constant region, and a connecting peptide) of each peptide chain are covalently attached to a transmembrane domain. In some embodiments, the sequence of a transmembrane domain is selected from a human leukocyte antigen (HLA). In some embodiments, the transmembrane domains for both peptide chains are the same. In other embodiments, the transmembrane domains for both peptide chains are different. 20 In a particular embodiment, the transmembrane domain comprises HLA-DRA, HLA-DRB1, or HLA-DRB2. In a specific embodiment, the transmembrane domain comprises the amino acid sequence of SEQ ID NO: 21 (HLA-DRA), SEQ ID NO: 22 (HLA-DRB1), or SEQ ID NO: 34 (HLA-DRB2). Alternatively, the transmembrane domain comprises a sequence having at least 70% sequence identity (i.e., at least 75% sequence identity, at least 80% sequence identity, at least 25   85% sequence identity, at least 90% sequence identity, at least 95% sequence identity, at least 96% sequence identity, at least 97% sequence identity, at least 98% sequence identity, or at least 99% sequence identity) to SEQ ID NO: 21, SEQ ID NO: 22, or SEQ ID NO: 34. In an embodiment, the transmembrane domain for one peptide chain comprises HLA-DRA and the transmembrane domain for the other peptide chain of the modified TCR comprises HLA-DRB, 30 such as HLA-DRB 1 or HLA-DRB2. In another particular embodiment, the transmembrane domain for one peptide chain of the modified TCR comprises the amino acid sequence of SEQ ID NO: 21 and the transmembrane domain for the other peptide chain of the modified TCR comprises the amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 34. 2025202995   29 Apr 2025

[0041] The peptide chains of the modified TCRs further comprise intracellular domains, each comprising a CD28 region and a CD3(^ IT AM region. In a particular embodiment, the CD28 region comprises the amino acid sequence of SEQ ID NO:23. In another embodiment, the CD3(^ IT AM region comprises the amino acid sequence of SEQ ID NO: 24. Alternatively, the constant region 5 comprises a sequence having at least 70% sequence identity (i.e., at least 75% sequence identity, at least 80% sequence identity, at least 85% sequence identity, at least 90% sequence identity, at least 95% sequence identity, at least 96% sequence identity, at least 97% sequence identity, at least 98% sequence identity, or at least 99% sequence identity) to SEQ ID NO: 23 or SEQ ID NO: 24. In a still further embodiment, the intracellular domain of each peptide chain of the modified 10 TCR comprises the amino acid sequence of SEQ ID NO: 23 and the amino sequence of SEQ ID NO: 24.

[0042] In an embodiment, each of the peptide chains of the modified TCR are the same as each other. In another embodiment, each of the two peptide chains in the modified TCR are different from each other. 15

[0043] Table 1 describes specific combinations of the peptide chains that dimerize to form a modified TCR. Table 1 Extracellular Domain Transmembrane Domain Intracellular Domain Name Variable Region Constant Region Connecting Peptide Peptide 1 Va-1 linker-WinZip-Bl GGCGG (SEQ ID NO: 1) HLA-DRA CD28-CD3^ ITAM Peptide 2 vp-i linker-WinZip-A2 GGCGG (SEQ ID NO: 1) HLA-DRB1 CD28-CD3(; ITAM Peptide 3 Va-1 GGSGG (SEQ ID NO:2)-Ig-CK GSG HLA-DRA CD28-CD3^ ITAM Peptide 4 vp-i GGSGG (SEQ ID NO:2)-Ig-CH-la GSG HLA-DRB1 CD28-CD3i; ITAM Peptide 5 Va-2 Ig-CK GSG HLA-DRA CD28-CD3£ ITAM Peptide 6 Vp-2 GGSGG (SEQ ID NO: 2)-IgG-CH-la GSG HLA-DRB2 CD28-CD3i; ITAM 2025202995   29 Apr 2025 Peptide 7 Vp-2 IgG-CH-lb GSG HLA-DRB2 CD28-CD3£ IT AM Peptide 8 Vp-2 IgM-CH-1 GSG HLA-DRB2 CD28-CD3£ IT AM

[0044] Table 2 describes particular peptide chains that may homodimerize or heterodimerize with each other or other peptide chains comprising an extracellular domain (comprising a variable region, a constant region, and a connecting peptide), a transmembrane domain, and an intracellular 5 domain. Table 2 Peptide Name Amino Acid Sequence Nucleic Acid Sequence P-NR-027 SEQ ID NO: 3 SEQ ID NO: 12 P-NR-028 SEQ ID NO: 4 SEQ ID NO: 14 P-NR-025 SEQ ID NO: 5 SEQ ID NO: 8 P-NR-026 SEQ ID NO: 6 SEQ ID NO: 10 PWH3O8 SEQ ID NO: 26 SEQ ID NO: 35 PWH295 SEQ ID NO: 27 SEQ ID NO: 36 PWH3O3 SEQ ID NO: 28 SEQ ID NO: 37 PWH305 SEQ ID NO: 29 SEQ ID NO: 38

[0045] The peptide chains of Table 1 or Table 2 may form homodimers or heterodimers to generate the modified TCR. For example, P-NR-025 (SEQ ID NO: 5) and P-NR-026 (SEQ ID NO: 6) may dimerize to form a modified TCR (FIG. 1). Alternatively, P-NR-027 (SEQ ID NO: 10   3) and P-NR-028 (SEQ ID NO: 4) may dimerize to form another modified TCR (FIG. 2). Additional peptide chain combinations to form chimeric TCRs are shown in Table 3 below. Table 3 Ig-CK Ig-CH-1 P-NR-025 (SEQ ID NO: 5) P-NR-026 (SEQ ID NO: 6) PWH3O8 (SEQ ID NO: 26) PWH295 (SEQ ID NO: 27) PWH3O8 (SEQ ID NO: 26) PWH3O3 (SEQ ID NO: 28) PWH3O8 (SEQ ID NO: 26) PWH305 (SEQ ID NO: 29) 2025202995   29 Apr 2025

[0046] SEQ ID NOs: 15-24, 31-34, and 39-46 are offered only as examples of suitable portions of the peptide chain comprising the modified TCRs (z. e., specific variable region, constant region, connecting peptide, transmembrane domain, CD28 region, and CD3£ ITAM region sequences) 5 but many variations on these sequences are also useful for anti-viral or anti-cancer therapeutic purposes. For example, polypeptides having at least 70% sequence identity (i.e., at least 75% sequence identity, at least 80% sequence identity, at least 85% sequence identity, at least 90% sequence identity, at least 95% sequence identity, at least 96% sequence identity, at least 97% sequence identity, at least 98% sequence identity, or at least 99% sequence identity) to any one of 10 SEQ ID NOs: 15-24, 31-34, and 39-46 are also useful for therapeutic purposes, provided that the molecule retains—broadly—the overall binding site, structure, and / or orientation of the individual SEQ ID NOs: 15-24, 31-34, and 39-46 molecules. III. Polynucleotides and vectors

[0047] Contemporary molecular biologists know how to make nucleic acids that express the 15 peptide chains described herein, and how to express such nucleic acids in cells to obtain the relevant proteins. Further embodiments provided herein include nucleic acids or polynucleotides that encode a peptide chain which comprise the modified TCR. For example, nucleic acids encoding the modified TCRs described herein are presented herein as SEQ ID NOs: 7-14 and 3538. The ordinary molecular biologist knows how to alter the nucleotide sequence of SEQ ID NO: 20   8, 10, 12, 14, and 35-38 to encode peptide chains of SEQ ID NOs: 5, 6, 3, 4, and 26-29, respectively, and appropriate variants thereof (e.g., variants having at least 70% identity (e.g., at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% to any one of SEQ ID NOs:5, 6, 3, and 4). Non-limiting examples of nucleic acids encoding the peptide chains of SEQ ID NOs: 5, 6, 3, 4, and 26-29 are provided 25 herein as SEQ ID NOs: 8, 10, 12, 14, and 35-38 respectively.

[0048] In certain embodiments, the nucleic acids described above can be expressed in a supporter cell line. Mammalian cell lines such as Chinese hamster ovary (CHO) cells or 293T cells are particularly suitable for these purposes. The proteins described herein are generally soluble, and will therefore be excreted from a producing cell unless they are modified for intracellular 30 retention. Proteins produced in this manner can be purified from the culture medium. Where desired, the proteins may be tagged with (e.g.) a poly-histidine tag or other such commercially common tags to facilitate purification. Proteins produced and purified in this manner can then be administered to a subject in need thereof as described below. 2025202995   29 Apr 2025

[0049] Alternatively, the nucleic acids described above can be expressed in primary T cells, such as T cells obtained from peripheral blood, tumors, and / or lymph nodes. The primary T cells may be harvested and manipulated as is conventional in the art. The primary T cells may be from a subject having a condition treatable with the modified TCR described herein. Alternatively, the 5 primary T cells may be from another subject having primary T cells which are immunocompatible with the subject to be treated.

[0050] Additionally or alternatively, the nucleic acids described herein can be incorporated into a vector (e.g., a transfection vector or a viral transduction vector). Such vectors can then be transfected or transduced into the subject’s own cells. In this way, the subject’s own cells will 10 produce the modified TCR. Non-limiting examples of vectors comprising the nucleic acids described above are provided herein as SEQ ID NOs: 7-14. The correlation of the vector with the peptide chain of the modified TCR is shown in Table 2, above. Figs. 3A-3D show embodiments of SEQ ID NOs: 8, 10, 12, and 14, respectively.

[0051] In some embodiments, the nucleic acid encoding the modified TCR are incorporated into 15 a cell. Such cells may translate the nucleic acid to encoding the modified TCR to express the TCR. The cells may be the subject’s own cells (e.g., autologous cells) or cells from an appropriate donor (e.g., heterologous cells). IV. Methods of prevention or treatment

[0052] The proteins, peptides, cells, nucleic acids, and vectors described above can be used to 20 treat and / or prevent and / or reduce the occurrence of viral infection and / or cancer. To treat and / or prevent a viral infection and / or cancer, the modified TCR, cells comprising the modified TCR, nucleic acids encoding the modified TCR, and vectors comprising the nucleic acids encoding the modified TCRs described herein can be administered to a subject in need thereof in a therapeutically effective amount. The subject may be symptomatic or asymptomatic. 25 Therapeutically effective amounts of these modified TCRs include but are not limited to 1 pg of the modified TCR per kg of subject body weight, 5 pg / kg, 10 pg / kg, 50 pg / kg, 100 pg / kg, 500 pg / kg, 1 mg / kg, 5 mg / kg, 10 mg / kg, 50 mg / kg, 100 mg / kg, 500 mg / kg, and 1 mg / kg or more.

[0053] Where the modified TCR, cells comprising the modified TCR, nucleic acids encoding the modified TCR, and vectors comprising nucleic acids encoding the modified TCRs are 30 administered, any suitable route of administration may be used, including but not limited to oral administration, intravenous injection, intramuscular injection, subcutaneous injection, and inhalation (e.g. aerosol inhalation). In a particular embodiment, the TCR is administered by 2025202995   29 Apr 2025 modifying T cells or NK cells to express the TCR, and then by infusing the modified immune cells into the patient.

[0054] In a preferred embodiment, the modified TCR is transfected into autologous T cells derived from a patient with cancer of infectious disease. T cells may be derived from whole blood, 5 a tumor, or a draining lymph node. In an embodiment, donor T cells may be used. The modified TCR described herein may be transfected into primary T cells as a nucleic acid, wherein the nucleic acid may be DNA or RNA in any suitable vector. The DNA vector may be an adenovirus. The nucleic acid may be RNA. The RNA may be in nanoparticle format such as is described in US 11,141,377, which is incorporated herein by reference. Transfection may be performed by 10 standard techniques, such as electroporation (for example as described in US 11,377,652 and US 2022 / 0025402, both of which are incorporated herein by reference) or by using the MaxCyte™ system (Rockville, USA). Autologous T cells thus transfected may be ex vivo enriched and expanded. For example, CD3 enriched T cells may be expanded in Immunocult™ (StemCell Technologies, Cambridge, USA) and IL-2. T cells may be administered to the patient in 15 therapeutically effective amounts. In some embodiments, the composition comprising the T cells manufactured by the methods described herein may be administered at a dosage of 102 to 1012 cells / kg body weight, 102 to 1010 cells / kg body weight, 105 to 109 cells / kg body weight, 105 to 108 cells / kg body weight, 105 to 107 cells / kg body weight, 107 to 109 cells / kg body weight, or 107 to 108 cells / kg body weight, including all integer values within those ranges. The number of T cells 20 will depend on the therapeutic use for which the composition is intended.

[0055] Where a nucleic acid encoding the modified TCR is to be transfected into a cell, such as a T cell, any suitable amount can be transfected into a cell, including (but not limited to) 10 ng, 50 ng, 100 ng, 500 ng, 1 pg, 5 pg, 10 pg, 50 pg, 100 pg, 500 pg, 1 mg, 5 mg, 10 mg, 50 mg, 100 mg, and 500 mg or more. To transfect subject cells with polynucleotides as described herein, it will be 25 useful to extract cells from the subject, transfect them according to known techniques, and then transfuse the transfected cells back into the subject. Electroporation is a particularly suitable transfection method {see, e.g., WO 20 / 14264 & WO 21 / 07315, each of which are herein incorporated by reference in their entireties). Particularly suitable cells include cells circulating throughout the body, such as circulating lymphocytes {e.g., T cells, NK cells). 30

[0056] Where a nucleic acid is to be transduced, a viral vector can be administered directly to the subject, or cells can be extracted for transduction and re-transfusion. The viral vector can be administered to the subject by any suitable route of administration, including but not limited to 2025202995   29 Apr 2025 intravenous injection, intramuscular injection, subcutaneous injection, and inhalation (e.g. aerosol inhalation).

[0057] Therapeutically effective virus amounts include but are not limited to lx 107 viral particles (VPs), 5xl07 VPs, IxlO8 VPs, 5xl08 VPs, IxlO9 VPs, 5xl09 VPs, IxlO10 VPs, or more than 5 IxlO10 VPs. Adenoviral vectors are particularly suitable for this purpose because of the large cargo capacity of the adenovirus. Suitable adenoviral vectors include those disclosed in WO 98 / 17783, WO 02 / 27007, WO 09 / 6479, & WO 14 / 31178, each of which is incorporated herein by reference in its entirety. Suitable methods for administering these adenoviral vectors are disclosed in WO 16 / 112188, which is herein incorporated by reference in its entirety. 10

[0058] The proteins, peptides, cells, nucleic acids, and vectors described above can be used to treat and / or prevent and / or reduce the occurrence of cancer in a patient. The cancer may be bladder cancer, bone cancer, brain cancer (including medulloblastoma, meningioma, neuroblastoma), breast cancer, cancer of the central nervous system, cervical cancer, colon cancer, colorectal cancer, esophageal cancer, eye cancer, gall bladder cancer, head and neck cancer, gastric cancer, 15 HIV / AIDS related cancer, kidney cancer, leukemia, (including acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), B cell leukemia (BCL), chronic lymphocytic cancer (CLL), chronic myeloid leukemia (CML), and chronic T cell lymphocytic leukemia (CTLL)), liver cancer, lung cancer (including non-small cell and small cell), lymphoma (including nonHodgkin lymphoma and Hodgkin lymphoma), melanoma, multiple myeloma, nasopharyngeal 20 cancer, oral cancer (including cancer of the mouth, tongue, salivary glands, or gums), neuroendocrine cancer, ovarian cancer, pancreatic cancer, prostate cancer, retinoblastoma, sarcoma, skin cancer, stomach cancer, testicular cancer, thyroid cancer, uterine cancer, and vaginal cancer. In a particular embodiment, the the patient may have bladder cancer, breast cancer, colon cancer, or pancreatic cancer. 25

[0059] The proteins, peptides, cells, nucleic acids, and vectors described above can be used to treat and / or prevent and / or reduce the occurrence of a viral infection in a patient. The virus may be either a DNA or an RNA virus. The patient may be suffering an infection from a DNA virus such as a single- or double-stranded virus. The DNA virus may belong to any family of DNA viruses, including, but not limited to, herpesviridae, adenoviridae, polyomavididae, and 30 poxviridae. Alternatively, the patient may be suffering an infection from an RNA virus, such as a single- or double-stranded virus. The RNA virus may belong to any family of RNA viruses, including, but not limited to, reoviridae, coronaviridae, picornaviridae, flaviviridae, hepeviridae, togaviridae, filoviridae, paramyxoviridae, pneumoviridae, rhabdoviridae, hantaviridae, and 2025202995   29 Apr 2025 orthomyxoviridae. In particular, the patient may be infected with rotavirus, coronavirus, SARS virus, poliovirus, rhinovirus, hepatitis A virus, yellow fever virus, west nile virus, hepatitis C virus, dengue fever virus, zika virus, rubella virus, sindbis virus, Chikungunya virus, Ebola virus, Marburg virus, measles virus, mumps virus, respiratory syncytial virus, rabies virus, influenza 5 virus A, influenza virus B, influenza virus C, influenza virus D, and human immunodeficiency virus. EMBODIMENTS

[0060] Embodiment 1: A modified T cell receptor (TCR) comprising a first peptide chain and a second peptide chain, wherein each peptide chain comprises: an extracellular domain; a 10 transmembrane domain; and an intracellular domain, wherein the extracellular domain comprises a variable region, a constant region, and a connecting peptide, wherein the variable region and the constant region are attached via a linker, wherein the constant region of the first peptide chain comprises an Ig-CK domain and the constant region of the second peptide chain comprises an Ig-CH-1 domain, and wherein either 1) the transmembrane domain of the first peptide chain 15 comprises an HLA-DRA domain and the transmembrane domain of the second peptide chain comprises an HLA-DRB domain, or 2) the transmembrane domain of the first peptide chain comprises an HLA-DRB domain and the transmembrane domain of the second peptide chain comprises an HLA-DRA domain.

[0061] Embodiment 2: The TCR of embodiment 1, wherein the linker is a flexible linker. 20

[0062] Embodiment 3: The TCR of embodiment 1 or 2, wherein the Ig-CH-1 domain is IgG-CH- la, IgG-CH-lb, or IgM-CH-1.

[0063] Embodiment 4: The TCR of any one of embodiments 1-3, wherein the HLA-DRB domain is HLA-DRB 1 or HLA-DRB2.

[0064] Embodiment 5: The TCR of any one of embodiments 1-4, wherein the variable regions on 25 each of the peptide chains are the same variable region.

[0065] Embodiment 6: The TCR of any one of embodiments 1-5, wherein the variable regions on each peptide chain are different from each other.

[0066] Embodiment 7: The TCR of any one of embodiments 1-6, wherein the intracellular domain comprises a CD28 region and a CD3(^ IT AM region. 30

[0067] Embodiment 8: The TCR of any one of embodiments 1-7, wherein the first peptide chain comprises: Ig-CK as the constant region, HLA-DRA as the transmembrane domain; and CD28 and CD3£ as the intracellular domain. 2025202995   29 Apr 2025

[0068] Embodiment 9: The TCR of embodiment 8, wherein the first peptide chain comprises SEQ ID NO: 39.

[0069] Embodiment 10: The TCR of embodiment 9, wherein the first peptide chain comprises SEQ ID NO: 5. 5

[0070] Embodiment 11: The TCR of embodiment 8, wherein the first peptide chain comprises SEQ ID NO: 43.

[0071] Embodiment 12: The TCR of embodiment 11, wherein the first peptide chain comprises SEQ ID NO: 26.

[0072] Embodiment 13: The TCR of any one of embodiments 1-7, wherein the second peptide 10 chain comprises: Ig-CH-1 as the constant region, HLA-DRB as the transmembrane domain, and CD28 and CD3£ as the intracellular domain.

[0073] Embodiment 14: The TCR of embodiment 13, wherein the second peptide chain comprises SEQ ID NO: 40.

[0074] Embodiment 15: The TCR of embodiment 14, wherein the second peptide chain comprises 15 SEQ ID NO: 6.

[0075] Embodiment 16: The TCR of embodiment 13, wherein the second peptide chain comprises SEQ ID NO: 44.

[0076] Embodiment 17: The TCR of embodiment 16, wherein the second peptide chain comprises SEQ ID NO: 27. 20

[0077] Embodiment 18: The TCR of embodiment 13, wherein the second peptide chain comprises SEQ ID NO: 45.

[0078] Embodiment 19: The TCR of embodiment 18, wherein the second peptide chain comprises SEQ ID NO: 28.

[0079] Embodiment 20: The TCR of embodiment 13, wherein the second peptide chain comprises 25 SEQ ID NO: 46.

[0080] Embodiment 21: The TCR of embodiment 20, wherein the second peptide chain comprises SEQ ID NO: 29.

[0081] Embodiment 22: The TCR of any one of embodiments 1-21, wherein the first peptide chain comprises Ig-CK as the constant region, HLA-DRA as the transmembrane domain; and 30 CD28 and CD3(^ as the intracellular domain; and the second peptide chain comprises Ig-CH-1 as 2025202995   29 Apr 2025 the constant region, HLA-DRB as the transmembrane domain, and CD28 and CD3(^ as the intracellular domain.

[0082] Embodiment 23: The TCR of embodiment 22, wherein the first peptide chain comprises SEQ ID NO: 39 and the second peptide chain comprises SEQ ID NO: 40. 5

[0083] Embodiment 24: The TCR of embodiment 23, wherein the first peptide chain further comprises SEQ ID NO: 15 and the second peptide chain further comprises SEQ ID NO: 16.

[0084] Embodiment 25: The TCR of embodiment 24, wherein the first peptide comprises SEQ ID NO: 5 and the second peptide chain comprises SEQ ID NO: 6.

[0085] Embodiment 26: The TCR of embodiment 22, wherein the first peptide chain comprises 10 SEQ ID NO: 43 and the second peptide chain comprises SEQ ID NO: 44.

[0086] Embodiment 27: The TCR of embodiment 26, wherein the first peptide chain further comprises SEQ ID NO: 30 and the second peptide chain further comprises SEQ ID NO: 31.

[0087] Embodiment 28: The TCR of embodiment 27, wherein the first peptide comprises SEQ ID NO: 26 and the second peptide chain comprises SEQ ID NO: 27. 15

[0088] Embodiment 29: The TCR of embodiment 22, wherein the first peptide chain comprises SEQ ID NO: 43 and the second peptide chain comprises SEQ ID NO: 44.

[0089] Embodiment 30: The TCR of embodiment 29, wherein the first peptide chain further comprises SEQ ID NO: 30 and the second peptide chain further comprises SEQ ID NO: 31.

[0090] Embodiment 31: The TCR of embodiment 30, wherein the first peptide comprises SEQ 20 ID NO: 26 and the second peptide chain comprises SEQ ID NO: 28.

[0091] Embodiment 32: The TCR of embodiment 22, wherein the first peptide chain comprises SEQ ID NO: 43 and the second peptide chain comprises SEQ ID NO: 44.

[0092] Embodiment 33: The TCR of embodiment 32, wherein the first peptide chain further comprises SEQ ID NO: 30 and the second peptide chain further comprises SEQ ID NO: 31. 25

[0093] Embodiment 34: The TCR of embodiment 33, wherein the first peptide comprises SEQ ID NO: 26 and the second peptide chain comprises SEQ ID NO: 29.

[0094] Embodiment 35: A cell comprising the TCR of any one of embodiments 1-34.

[0095] Embodiment 36: A nucleic acid encoding the TCR of any one of embodiments 1-34.

[0096] Embodiment 37: A vector comprising the nucleic acid of embodiment 36 2025202995   29 Apr 2025

[0097] Embodiment 38: A method for reducing the occurrence of or treating cancer or a viral infection in a patient in need thereof, the method comprising administering a pharmaceutical composition to the patient, wherein the pharmaceutical composition comprises a therapeutically effective amount of the modified TCR of any one of claims 1-34 or a nucleic acid encoding the 5 modified TCR of any one of embodiments 1-34.

[0098] Embodiment 39: The method of embodiment 38 wherein the pharmaceutical comprises a vector that comprises the nucleic acid.

[0099] Embodiment 40: The method of embodiments 38 or 39, wherein the pharmaceutical composition comprises a cell comprising the modified TCR or a nucleic acid encoding the 10 modified TCR.

[00100] Embodiment 41: The method of any one of claims 38-40, wherein the cancer is selected from the group consisting of bladder cancer, bone cancer, brain cancer, breast cancer, cancer of the central nervous system, cervical cancer, colon cancer, colorectal cancer, esophageal cancer, eye cancer, gall bladder cancer, head and neck cancer, gastric cancer, HIV / AIDS related 15 cancer, kidney cancer, leukemia, liver cancer, lung cancer, lymphoma, melanoma, multiple myeloma, nasopharyngeal cancer, oral cancer, neuroendocrine cancer, ovarian cancer, pancreatic cancer, prostate cancer, retinoblastoma, sarcoma, skin cancer, stomach cancer, testicular cancer, thyroid cancer, uterine cancer, and vaginal cancer.

[00101] Embodiment 42: The method of any one of claims 38-40, wherein the viral 20 infection is caused by a virus from a viral family selected from the group consisting of herpesviridae,   adenoviridae,   polyomavididae, poxviridae, reoviridae, coronaviridae, picomaviridae,   flaviviridae,   hepeviridae, togaviridae, filoviridae, paramyxoviridae, pneumoviridae, rhabdoviridae, hantaviridae, and orthomyxoviridae.

[00102] Embodiment 43: Use of the TCR of claim 1, the cell of claim 35, the nucleic acid 25 of claim 36 or the vector of claim 37 for preventing or treating a cancer or a viral infection in a patient in need thereof. EXAMPLES

[00103] The following example is provided to further illustrate the invention disclosed 30 herein but should not be construed as in any way limiting its scope.

[00104] Example 1: Cloning of TCR constructs 2025202995   29 Apr 2025

[00105] The HLA-DRA or HLA-DRB1 connecting peptide plus transmembrane (CP-TM) region DNA template was built by annealing long partially overlapping oligonucleotides (IDT). Each of these CP-TM sequences was fused by overlap extension PCR (OE-PCR) to a CD28 intracellular (IC) plus CD3^ (IC) sequence obtained from a previously cloned template. DNA 5 templates encoding extracellular constant domains from Ig-CK or Ig-CH-1 were obtained by PCR from a previously cloned pAO156 template. The extracellular constant domains composed of Linker-WinZip-B 1 or Linker-WinZip-A2 coiled-coil domain were obtained as gBlock DNA fragments (IDT) encoding either Linker-WinZip-B 1 or Linker-WinZip-A2. Each of these extracellular constant domains was fused by OE-PCR to either the HLA-DRA or HLA-DRB 1 CP-10 TM plus CD28- CD3(^ intracellular sequences. These invariable-CP-TM-IC sequences were cloned into a multi-purpose expression vector (pRNi). Invariable-CP-TM-IC inserts were cloned by a blunt ligation at the 5’ end so as to regenerate an EcoRV site, and a PacI overlap at the 3’ end. The resulting invariable-CP-TM-IC constructs in pRNi have an Ncol restriction site directly upstream of the coding sequence. As such, any TCR Va or VP sequence can be designed or 15 amplified with a Bsal or Esp3I restriction site at the 5’ end and a blunt, phosphorylated 3’ end and cloned into one of the invariable-CP-TM-IC vectors digested with Ncol and EcoRV. FIGs. 3A-3D illustrate particular embodiments of the cloned modified TCR constructs.

[00106] Example 2: mRNA synthesis and effector cell electroporation

[00107] The modified TCR constructs of Example 1 were inserted into an expression 20 vector. The constructs were flanked upstream by a T7 promoter and a 5’ UTR and downstream by a 3’ UTR adopted from mouse hemoglobin alpha, and a short poly (A) followed by an Aarl linearization site. This allows for T7-based in vitro transcription of the modified TCR after linearization of the final vectors P-NR-025, P-NR-026, P-NR-027, and P-NR-028 with Aarl. Activated natural killer (aNK) cells were electroporated with in vitro transcribed and 25 polyadenylated mRNA (NEB Cat Nos. E2040S and M0276S) at 3 pg mRNA per 3xl06 cells in 50 pL using the BIO-RAD Gene Pulser II with 2 mm-gap cuvettes. Electroporated aNKs were incubated overnight at lx 106 cells per mL in full RPMI media (Coming RPMI 1640 with L-Glu, supplemented with 10% FBS and IxPSA) in wells of a 6-well TC-treated plate at 37°C and 5% CO2. 30

[00108] Example 3: Killing assay

[00109] Target D3C6 cells (i.e., KG-1 cells in which all MHC-I alleles have been knocked out) stably expressing HLA-A2 were pulsed at 6.4xl05 cells / mL in 4.4 mL each with either 4 2025202995   29 Apr 2025 pg / mL of hCMV pp65 NLV peptide - HLA-A*0201-restricted (NLVPMVATV (SEQ ID NO:25), in DMSO) or an equivalent volume of DMSO. The pulsed target cells were incubated overnight in full IMDM media (ATCC Iscove’s IMDM supplemented with 10% FBS and lx PSA) at 37°C and 5% CO2 in T-25 flasks. After 20-24 hr from the electroporation, the aNK effector cells of 5 Example 2 were washed in PBS (without calcium or magnesium) and resuspended in full RPMI 1640 media. The effector aNK were then counted and serially diluted to from IxlO5 to 6.25xl04 live effector cells per well and deposited into round-bottom 96-well plates. Unbound peptide or DMSO was removed from pulsed target cells by washing once with full RPMI media and twice with PBS. Washed target cells were resuspended in 2 mL PBS with 20 pL of Calcein-AM (Fisher 10 Scientific Cat No. C3099) each and incubated at 37°C and 5% CO2 for 20 minutes with gentle shaking. Calcein-loaded target cells were washed with PBS and then with full RPMI before resuspending in 10 mL full RPMI and counted. Target cells were loaded to wells of the 96-well round bottom plate at 5xl03 live target cells per well together with their effector cells. Killing assay plates were centrifuged at 400xg for 5 min and incubated for 4 hours at 37°C and 5% CO2. 15 After incubation, 22 pL of 9% (v / v) Triton X-100 (Sigma Aldrich) was added to maximum lysis control wells and plates incubated at room temperature for 5 minutes. Killing plates were centrifuged again and 100 pL supernatant transferred to 96-well Immuno assay plates for excitation at 485 ± 20nm and emission read at 528 ± 20nm wavelength. Each sample was plated in triplicate. 20

[00110] Figs. 4A-4E demonstrate the % specific target cell lysis of HLA-A2 positive target cells pulsed with pp65-NLV or DMSO (control) and exposed to either TCRaP-ITAM fusion-electroporated aNK cells or control aNK cells. “P-NR-025 + P-NR-026 aNK” of FIG. 4A denotes the TCRaP-ITAM fusions shown in Fig. 1. “P-NR-027 + P-NR-028 aNK” of FIG. 4B denotes the TCRaP-ITAM fusions shown in Fig. 2. “P-NR-002 + P-NR-016 + CD3y5 aNK” of FIG. 4C 25 denotes wild-type TCRaP containing the same anti-pp65-NLV-HLA-A2 variable domains as the other constructs, and co-electroporated with CD3y8 to serve as a positive killing control. “P-WT-173” of FIG. 4D is also a positive killing control, but stably expressing the same wild-type anti-pp65-NLV-HLA-A2 TCRaP and CD3y8. A negative control is depicted by aNK electroporated with GFP alone (FIG. 4E). P-NR-025 + P-NR-026, P-NR-027 + P-NR-028, P-NR-002 + P-NR- 30   016, and P-WT-173 all contained the same variable TCRaP sequence pairs previously determined to bind to NLV peptide on HLA-A*02. Error bars only depict ± standard deviation of technical replicates. 2025202995   29 Apr 2025

[00111] Example 4: Chimeric TCR expression and cytotoxicity of P-NR-025 + P-NR-026, P-NR-025 + PWH295, PWH308 + PWH305, or PWH308 + PWH305 in activated NK cells

[00112] aNK (NK92) cells were washed with RPMI buffer and resuspended in RPMI at a 5 concentration of 107 cells / 50 pL. 5 pg of mRNA encoding a first and second peptide chain were combined with 107 aNK cells in 50 pL RPMI to a 2 mm cuvette. The cuvettes were subjected to three 20 ms pulses of 200 V with a BioRad GenePulser II. Electroporated cells were transferred to culture media (Coming RPMI 1640 with L-Glu, supplemented with 10% FBS and IxPSA) containing IL-2 and incubated overnight. 10

[00113] Following overnight incubation, 2xl05 cells from each sample were obtained and washed with a PBS / BSA / EDTA buffer. The cells were resuspended in 100 pL of the wash buffer. 5 pL of PE-HLA-A*0201, NLVPMVATV-PE, or HLA-A2 dextramer negative control were added to each sample. The samples were incubated at 4°C for 20 minutes, washed with PBS / BSA / EDTA and resuspended in 200 pL. The cells were analyzed via flow cytometry. Fig. 5 15 depicts the expression of various chimeric TCRs in the electroporated aNKs.

[00114] Following overnight incubation after electroporation, the aNKs were washed three times and incubated at a 10:1 (effector:target) ratio with HLA-A2 stable KG-1 cells stained with calcein AM. After a 4-hour incubation, the supernatant was obtained and analyzed for the fluorescence of calcein AM. Fig. 6 shows the % specific killing of the target cells by aNK cells 20 expressing modified TCRs described herein.

[00115] Example 5: Chimeric TCR expression and cytotoxicity of PWH308 + PWH305 and PWH308 + PWH305 in primary T cells

[00116] Human primary T cells were obtained from donor derived leukopacks (Charles River, Wilmington, USA). The peripheral blood mononuclear cells (PBMCs) were separated via 25 ficoll gradient and washed with KI00 buffer and resuspended in KI00 at a concentration of 107 cells / 100 pL. CD3-enriched T cells were then expanded in ImmunoCult™ (StemCell Technologies, Cambridge, USA) and IL-2. 10 pg of mRNA encoding a first and second peptide chain were combined with 107 T cells in 100 pL KI00 buffer to a 2 mm cuvette. The cells were electroporated according to the electroporation protocol described in US 11,377,652 and US 30   20220025402, both of which are incorporated herein by reference. Electroporated cells were transferred to culture media and incubated overnight. 2025202995   29 Apr 2025

[00117] Following overnight incubation, 2xl05 cells from each sample were obtained and washed with a PBS / BSA / EDTA buffer. The cells were resuspended in 100 pL of the wash buffer. 5 pL of PE-HLA-A*0201, NLVPMVATV-PE, or HLA-A2 dextramer negative control were added to each sample. The samples were incubated at 4°C for 20 minutes, washed twice with 5 PBS / BSA / EDTA and resuspended in 200 pL. The cells were analyzed via flow cytometry. Fig. 7 depicts the expression of various chimeric TCRs in the electroporated primary T cells.

[00118] Following overnight incubation after electroporation, the primary T cells were washed three times and incubated at a 10:1 (effector:target) ratio with HLA-A2 stable KG-1 cells stained with calcein AM. After a 4 hour incubation, the supernatant was obtained and analyzed 10 for the fluorescence of calcein AM. Fig. 8 shows the % specific killing of the target cells by primary T cells expressing modified TCRs described herein.

[00119] Example 6: Transfection of Patient-derived T cells with modified TCR

[00120] Patient T cells are derived from whole peripheral blood or isolated from a tumor or draining lymph nodes. The T cells are electroporated with a modified TCR as described herein. 15 The electroporated T cells are grown ex vivo to a clinically efficacious number of cells and a therapeutically relevant number of cells are administered to the patient.

[00121] All references, including publications, patent applications, and patents, cited herein are hereby incorporated by reference to the same extent as if each reference were individually and specifically indicated to be incorporated by reference and were set forth in its entirety herein. 20

[00122] The use of the terms “a” and “an” and “the” and “at least one” and similar referents in the context of describing the invention (especially in the context of the following claims) are to be construed to cover both the singular and the plural, unless otherwise indicated herein or clearly contradicted by context. The use of the term “at least one” followed by a list of one or more items (for example, “at least one of A and B”) is to be construed to mean one item selected from the 25 listed items (A or B) or any combination of two or more of the listed items (A and B), unless otherwise indicated herein or clearly contradicted by context. The terms “comprising,” “having,” “including,” and “containing” are to be construed as open-ended terms (i.e., meaning “including, but not limited to,”) unless otherwise noted. Recitation of ranges of values herein are merely intended to serve as a shorthand method of referring individually to each separate value falling 30 within the range, unless otherwise indicated herein, and each separate value is incorporated into the specification as if it were individually recited herein. All methods described herein can be performed in any suitable order unless otherwise indicated herein or otherwise clearly contradicted by context. The use of any and all examples, or exemplary language (e.g., “such as”) provided 2025202995   29 Apr 2025 herein, is intended merely to better illuminate the invention and does not pose a limitation on the scope of the invention unless otherwise claimed. No language in the specification should be construed as indicating any non-claimed element as essential to the practice of the invention.

[00123] Particular embodiments of this invention are described herein, including the best 5 mode known to the inventors for carrying out the invention. Variations of those particular embodiments may become apparent to those of ordinary skill in the art upon reading the foregoing description. The inventors expect skilled artisans to employ such variations as appropriate, and the inventors intend for the invention to be practiced otherwise than as specifically described herein. Accordingly, this invention includes all modifications and equivalents of the subject matter 10 recited in the claims appended hereto as permitted by applicable law. Moreover, any combination of the above-described elements in all possible variations thereof is encompassed by the invention unless otherwise indicated herein or otherwise clearly contradicted by context. 2025202995   29 Apr 2025 Sequence listing SEQ ID NO: Description Sequence 1 Linker GGCGG 2 Linker GGSGG 3 P-NR-027 MKSLRVLLVILWLQLSWVWSQQKEVEQNSGPLSVPEGAIASLNCT YSDRGSQSFFWYRQYSGKSPELIMSIYSNGDKEDGRFTAQLNKASQ YVSLLIRDSQPSDSATYLCAVNVPLSYQLTFGKGTKLSVIPNAGSST GSSTGPGSTSVDELQAEVDQLQDENYALKTKVAQLRKKVEKLASG GCGGEFDAPSPLPETTENVVCALGLTVGLVGIIIGTIFIIRSKRSRLLH SDYMNMTPRRPGPTRKHYQPYAPPRDFAAYRSRVKFSRSADAPAY QQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPQRRKNPQE GLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDT YDALHMQALPPR 4 P-NR-028 MLSLLLLLLGLGSVFSAVISQKPSRDICQRGTSLTIQCQVDSQVTMM FWYRQQPGQSLTLIATANQGSEATYESGFVIDKFPISRPNLTFSTLTV SNMSPEDSSIYLCSVAGTIDEQYFGPGTRLTVTESGGTSGSTSGTGST TVAQLRERVKTLRAQNYELESEVQRLREQVAQLASGGCGGRARSE SAQSKMLSGVGGFVLGLLFLGAGLFIRSKRSRLLHSDYMNMTPRRP GPTRKHYQPYAPPRDFAAYRSRVKFSRSADAPAYQQGQNQLYNEL NLGRREEYDVLDKRRGRDPEMGGKPQRRKNPQEGLYNELQKDKM AEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPP R 5 P-NR-025 MKSLRVLLVILWLQLSWVWSQQKEVEQNSGPLSVPEGAIASLNCT YSDRGSQSFFWYRQYSGKSPELIMSIYSNGDKEDGRFTAQLNKASQ YVSLLIRDSQPSDSATYLCAVNVPLSYQLTFGKGTKLSVIPNGGSGG RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNA LQS GNS QES VTEQDSKDSTYSLS STLTLS KADYEKHKV YACE VTHQ GLSSPVTKSFNRGECGSGEFDAPSPLPETTENVVCALGLTVGLVGIII GTIFIIRSKRSRLLHSDYMNMTPRRPGPTRKHYQPYAPPRDFAAYRS RVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPE MGGKPQRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHD GLYQGLSTATKDTYDALHMQALPPR 6 P-NR-026 MLSLLLLLLGLGSVFSAVISQKPSRDICQRGTSLTIQCQVDSQVTMM FWYRQQPGQSLTLIATANQGSEATYESGFVIDKFPISRPNLTFSTLTV SNMSPEDSSIYLCSVAGTIDEQYFGPGTRLTVTEGGSGGASTKGPSV FPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFP AVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEP KSCGSGRARSESAQSKMLSGVGGFVLGLLFLGAGLFIRSKRSRLLH SDYMNMTPRRPGPTRKHYQPYAPPRDFAAYRSRVKFSRSADAPAY QQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPQRRKNPQE GLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDT YDALHMQALPPR 7 P-NR-021 plasmid AGCTAGCTTTAATACGACTCACTATAAGGAAATAAGAGAGAAA AGAAGAGTAAGAAGAAATATAAGAGCCACCATGGGCTAGTACA GATATCTGGTGGAAGAACTGTTGCGGCGCCATCAGTGTTCATCT TTCCCCCTAGCGACGAGCAGCTGAAGAGTGGCACAGCTTCCGTG GTCTGCCTGCTGAACAATTTCTACCCCCGGGAAGCCAAGGTGCA 2025202995   29 Apr 2025 GTGGAAAGTCGATAACGCTCTGCAGTCTGGAAATAGTCAGGAGT CAGTGACTGAACAGGACAGCAAGGATTCCACCTATTCTCTGAGC TCCACCCTGACACTGTCTAAAGCAGACTACGAGAAGCACAAAGT CTATGCCTGTGAAGTCACTCACCAGGGTCTGTCTTCACCAGTCAC CAAATCCTTCAATAGGGGGGAATGCGGCAGTGGTGAGTTTGATG CTCCAAGCCCTCTCCCAGAGACTACAGAGAACGTGGTGTGTGCC CTGGGCCTGACTGTGGGTCTGGTGGGCATCATTATTGGGACCAT CTTCATCATCAGGAGTAAGAGGAGCAGGCTCCTGCACAGTGACT ACATGAACATGACTCCCCGCCGCCCCGGGCCCACCCGCAAGCAT TACCAGCCCTATGCCCCACCACGCGACTTCGCAGCCTATCGCTC CAGAGTGAAGTTCAGCAGGAGCGCAGACGCCCCCGCGTACCAG CAGGGCCAGAACCAGCTCTATAACGAGCTCAATCTAGGACGAA GAGAGGAGTACGATGTTTTGGACAAGAGACGTGGCCGGGACCC TGAGATGGGGGGAAAGCCGCAGAGAAGGAAGAACCCTCAGGAA GGCCTGTACAATGAACTGCAGAAAGATAAGATGGCGGAGGCCT ACAGTGAGATTGGGATGAAAGGCGAGCGCCGGAGGGGCAAGGG GCACGATGGCCTTTACCAGGGTCTCAGTACAGCCACCAAGGACA CCTACGACGCCCTTCACATGCAGGCCCTGCCCCCTCGCTGATTA ATTAAGCTGCCTTCTGCGGGGCTTGCCTTCTGGCCATGCCCTTCT TCTCTCCCTTGCACCTGTACCTCTTGGTCTTTGAATAAAGCCTGA GTAGGAAGAAAAAAAAAAAAAAAAAAAAAAAGCAGGTGGCGG CCGCAGGTAAGCCAGCCCAGGCCTCGCCCTCCAGCTCAAGGCGG GACAGGTGCCCTAGAGTAGCCTGCATCCAGGGACAGGCCCCAG CCGGGTGCTGACACGTCCACCTCCATCTCTTCCTCAGGTCTGCCC GGGTGGCATCCCTGTGACCCCTCCCCAGTGCCTCTCCTGGTCGTG GAAGGTGCTACTCCAGTGCCCACCAGCCTTGTCCTAATAAAATT AAGTTGCATCATTTTGTTTGACTAGGTGTCCTTGTATAATATTAT GGGGTGGAGGCGGGTGGTATGGAGCAAGGGGCCCAAGTTAACT TGTTTATTGCAGCTTATAATGGTTACAAATAAAGCAATAGCATC ACAAATTTCACAAATAAAGCATTTTTTTCACTGCATTCTAGTTGT GGTTTGTCCAAACTCATCAATGTATCTTATCATGTCTGGATCCGC TTCAGGCACCGGGCTTGCGGGTCATGCACCAGGTGCGCGGTCCT TCGGGCACCTCGACGTCGGCGGTGACGGTGAAGCCGAGCCGCTC GTAGAAGGGGAGGTTGCGGGGCGCGGAGGTCTCCAGGAAGGCG GGCACCCCGGCGCGCTCGGCCGCCTCCACTCCGGGGAGCACGAC GGCGCTGCCCAGACCCTTGCCCTGGTGGTCGGGCGAGACGCCGA CGGTGGCCAGGAACCACGCGGGCTCCTTGGGCCGGTGCGGCGCC AGGAGGCCTTCCATCTGTTGCTGCGCGGCCAGCCTGGAACCGCT CAACTCGGCCATGCGCGGGCCGATCTCGGCGAACACCGCCCCCG CTTCGACGCTCTCCGGCGTGGTCCAGACCGCCACCGCGGCGCCG TCGTCCGCGACCCACACCTTGCCGATGTCGAGCCCGACGCGCGT GAGGAAGAGTTCTTGCAGCTCGGTGACCCGCTCGATGTGGCGGT CCGGGTCGACGGTGTGGCGCGTGGCGGGGTAGTCGGCGAACGC GGCGGCGAGGGTGCGTACGGCCCGGGGGACGTCGTCGCGGGTG GCGAGGCGCACCGTGGGCTTGTACTCGGTCATGGTGGCCTGCAG AGTCGCTCTGTGTTCGAGGCCACACGCGTCACCTTAATATGCGA AGTGGACCTGGGACCGCGCCGCCCCGACTGCATCTGCGTGTTTT CGCCAATGACAAGACGCTGGGCGGGGTTTGTGTCATCATAGAAC TAAAGACATGCAAATATATTTCTTCCGGGGACACCGCCAGCAAA CGCGAGCAACGGGCCACGGGGATGAAGCAGCTGCGCCACTCCC TGAAGATCCATCGTCTCCTAACAAGTTACATCACTCCTGCCCTTC 2025202995   29 Apr 2025 CTCACCCTCATCTCCATCACCTCCTTCATCTCCGTCATCTCCGTC ATCACCCTCCGCGGCAGCCCCTTCCACCATAGGTGGAAACCAGG GAGGCAAATCTACTCCATCGTCAAAGCTGCACACAGTCACCCTG ATATTGCAGGTAGGAGCGGGCTTTGTCATAACAAGGTCCTTAAT CGCATCCTTCAAAACCTCAGCAAATATATGAGTTTGTAAAAAGA CCATGAAATAACAGACAATGGACTCCCTTAGCGGGCCAGGTTGT GGGCCGGGTCCAGGGGCCATTCCAAAGGGGAGACGACTCAATG GTGTAAGACGACATTGTGGAATAGCAAGGGCAGTTCCTCGCCTT AGGTTGTAAAGGGAGGTCTTACTACCTCCATATACGAACACACC GGCGACCCAAGTTCCTTCGTCGGTAGTCCTTTCTACGTGACTCCT AGCCAGGAGAGCTCTTAAACCTTCTGCAATGTTCTCAAATTTCG GGTTGGAACCTCCTTGACCACGATGCTTTCCAAACCACCCTCCTT TTTTGCGCCTGCCTCCATCACCCTGACCCCCGCTGCGCGGGGGC ACGTCAGGCTCACCATCTGGGCCGCCTTCTTGGTGGTATTCAAA ATAATCGGCTTCCCCTACAGGGTGGAAAAATGGCCTTCTACCTG GAGGGGGCCTGCGCGGTGGAGACCCGGATGATGATGACTGACT ACTGGGACTCCTGGGCCTCTTTTCTCCACGTCCACGACCTCTCCC CCTGGCTCTTTCACGACTTCCCCCCCTGGCTCTTTCACGTCCTCT ACCCCGGCGGCCTCCACTACCTCCTCGACCCCGGCCTCCACTAC CTCCTCGACCCCGGCCTCCACTGCCTCCTCGACCCCGGCCTCCAC CTCCTGCTCCTGCCCCTCCCGCTCCTGCTCCTGCTCCTGTTCCACC GTGGGTCCCTTTGCAGCCAATGCAACTTGGACGTTTTTGGGGTCT CCGGACACCATCTCTATGTCTTGGCCCTGATCCTGAGCCGCCCG GGGCTCCTGGTCTTCCGCCTCCTCGTCCTCGTCCTCTTCCCCGTC CTCGTCCATGTGCCATGATGGCGGCCTGCAGCTGTGTTCGAGGC CGCGCGTGTCACCTTAATATGCGAAGTGGACCTGGGACCGCGCC GCCCCGACTGCATCTGCGTGTTCGAGTTCGCCAATGACAAGACG CTGGGCGGGGAGATCCCCCTTATTAACCCTAAACGGGTAGCATA TGCTTCCCGGGTAGTAGTATATACTATCCAGACTAACCCTAATTC AATAGCATATGTTACCCAACGGGAAGCATATGCTATCGAATTAG GGTTAGTAAAAGGGTCCTAAGGAACAGCGATCTGGATAGCATAT GCTATCCTAATCTATATCTGGGTAGCATATGCTATCCTAATCTAT ATCTGGGTAGCATAGGCTATCCTAATCTATATCTGGGTAGCATAT GCTATCCTAATCTATATCTGGGTAGTATATGCTATCCTAATTTAT ATCTGGGTAGCATAGGCTATCCTAATCTATATCTGGGTAGCATAT GCTATCCTAATCTATATCTGGGTAGTATATGCTATCCTAATCTGT ATCCGGGTAGCATATGCTATCCTCATGCATATACAGTCAGCATA TGATACCCAGTAGTAGAGTGGGAGTGCTATCCTTTGCATATGCC GCCACCTCCCAAGGAGATCTGTCGACATCGATGGGCGCGGGTGT ACACTCCGCCCATCCCGCCCCTAACTCCGCCCAGTTCCGCCCATT CTCCGCCTCATGGCTGACTAATTTTTTTTATTTATGCAGAGGCCG AGGCCGCCTCGGCCTCTGAGCTATTCCAGAAGTAGTGAGGAGGC TTTTTTGGAGGCCTAGGCTTTTGCAAAAAGCTAATTCGGCGTAAT CTGCTGCTTGCAAACAAAAAAACCACCGCTACCAGCGGTGGTTT GTTTGCCGGATCAAGAGCTACCAACTCTTTTTCCGAAGGTAACT GGCTTCAGCAGAGCGCAGATACCAAATACTGTCCTTCTAGTGTA GCCGTAGTTAGGCCACCACTTCAAGAACTCTGTAGCACCGCCTA CATACCTCGCTCTGCTGAAGCCAGTTACCAGTGGCTGCTGCCAG TGGCGATAAGTCGTGTCTTACCGGGTTGGACTCAAGAGATAGTT ACCGGATAAGGCGCAGCGGTCGGGCTGAACGGGGGGTTCGTGC ACACAGCCCAGCTTGGAGCGAACGACCTACACCGAACTGAGAT 2025202995   29 Apr 2025 ACCTACAGCGTGAGCTATGAGAAAGCGCCACGCTTCCCGAAGG GAGAAAGGCGGACAGGTATCCGGTAAGCGGCAGGGTCGGAACA GGAGAGCGCACGAGGGAGCTTCCAGGGGGAAACGCCTGGTATC TTTATAGTCCTGTCGGGTTTCGCCACCTCTGACTTGAGCGTCGAT TTTTGTGATGCTCGTCAGGGGGGCGGAGCCTATGGAAAAACGCC AGCAACGCAAGCTAGAGTTTAAACTTGACAGATGAGACAATAA CCCTGATAAATGCTTCAATAATATTGAAAAAGGAAAAGTATGAG TATTCAACATTTCCGTGTCGCCCTTATTCCCTTTTTTGCGGCATTT TGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTAAA AGATGCAGAAGATCACTTGGGTGCGCGAGTGGGTTACATCGAAC TGGATCTCAACAGCGGTAAGATCCTTGAGAGTTTTCGCCCCGAA GAACGTTTCCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGC GCGGTATTATCCCGTATTGATGCCGGGCAAGAGCAACTCGGTCG CCGCATACACTATTCTCAGAATGACTTGGTTGAATACTCACCAG TCACAGAAAAGCATCTTACGGATGGCATGACAGTAAGAGAATTA TGCAGTGCTGCCATAACCATGAGTGATAACACTGCGGCCAACTT ACTTCTGACAACTATCGGAGGACCGAAGGAGCTAACCGCTTTTT TGCACAACATGGGGGATCATGTAACTCGCCTTGATCGTTGGGAA CCGGAGCTGAATGAAGCCATACCAAACGACGAGCGTGACACCA CGATGCCTGTAGCAATGGCAACAACGTTGCGAAAACTATTAACT GGCGAACTACTTACTCTAGCTTCCCGGCAACAACTAATAGACTG GATGGAGGCGGATAAAGTTGCAGGACCACTTCTGCGCTCGGCAC TTCCGGCTGGCTGGTTTATTGCTGATAAATCAGGAGCCGGTGAG CGTGGGTCACGCGGTATCATTGCAGCACTGGGGCCGGATGGTAA GCCCTCCCGTATCGTAGTTATCTACACTACGGGGAGTCAGGCAA CTATGGATGAACGAAATAGACAGATCGCTGAGATAGGTGCCTCA CTGATTAAGCATTGGTAAGGATAAATTTCTGGTAAGGAGGACAC GTATGGAAGTGGGCAAGTTGGGGAAGCCGTATCCGTTGCTGAAT CTGGCATATGTGGGAGTATAAGACGCGCAGCGTCGCATCAGGCA TTTTTTTCTGCGCCAATGCAAAAAGGCCATCCGTCAGGATGGCC TTTCGGCATAACTAGTGAGGCTCCGGTGCCCGTCAGTGGGCAGA GCGCACATCGCCCACAGTCCCCGAGAAGTTGGGGGGAGGGGTC GGCAATTGAACCGGTGCCTAGAGAAGGTGGCGCGGGGTAAACT GGGAAAGTGATGTCGTGTACTGGCTCCGCCTTTTTCCCGAGGGT GGGGGAGAACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTCT TTTTCGCAACGGGTTTGCCGCCAGAACACAGGTAAGTGCCGTGT GTGGTTCCCGCGGGCCTGGCCTCTTTACGGGTTATGGCCCTTGCG TGCCTTGAATTACTTCCACCTGGCTGCAGTACGTGATTCTTGATC CCGAGCTTCGGGTTGGAAGTGGGTGGGAGAGTTCGAGGCCTTGC GCTTAAGGAGCCCCTTCGCCTCGTGCTTGAGTTGAGGCCTGGCC TGGGCGCTGGGGCCGCCGCGTGCGAATCTGGTGGCACCTTCGCG CCTGTCTCGCTGCTTTCGATAAGTCTCTAGCCATTTAAAATTTTT GATGACCTGCTGCGACGCTTTTTTTCTGGCAAGATAGTCTTGTAA ATGCGGGCCAAGACGATCTGCACACTGGTATTTCGGTTTTTGGG GCCGCGGGCGGCGACGGGGCCCGTGCGTCCCAGCGCACATGTTC GGCGAGGCGGGGCCTGCGAGCGCGGCCACCGAGAATCGGACGG GGGTAGTCTCAAGCTGGCCGGCCTGCTCTGGTGCCTGGCCTCGC GCCGCCGTGTATCGCCCCGCCCTGGGCGGCAAGGCTGGCCCGGT CGGCACCAGTTGCGTGAGCGGAAAGATGGCCGCTTCCCGGCCCT GCTGCAGGGAGCTCAAAATGGAGGACGCGGCGCTCGGGAGAGC GGGCGGGTGAGTCACCCACACAAAGGAAAAGGGCCTTTCCGTC 2025202995   29 Apr 2025 CTCAGCCGTCGCTTCATGTGACTCCACGGAGTACCGGGCGCCGT CCAGGCACCTCGATTAGTTCTCGAGCTTTTGGAGTACGTCGTCTT TAGGTTGGGGGGAGGGGTTTTATGCGATGGAGTTTCCCCACACT GAGTGGGTGGAGACTGAAGTTAGGCCAGCTTGGCACTTGATGTA ATTCTCCTTGGAATTTGCCCTTTTTGAGTTTGGATCTTGGTTCATT CTCAAGCCTCAGACAGTGGTTCAAAGTTTTTTTCTTCCATTTCAG GTGTCGTGAAA 8 P-NR-025 plasmid AGCTAGCTTTAATACGACTCACTATAAGGAAATAAGAGAGAAA AGAAGAGTAAGAAGAAATATAAGAGCCACCATGAAATCCTTGA GAGTTTTACTAGTGATCCTGTGGCTTCAGTTGAGCTGGGTTTGGA GCCAACAGAAGGAGGTGGAGCAGAATTCTGGACCCCTCAGTGTT CCAGAGGGAGCCATTGCCTCTCTCAACTGCACTTACAGTGACCG AGGTTCCCAGTCCTTCTTCTGGTACAGACAATATTCTGGGAAAA GCCCTGAGTTGATAATGTCCATATACTCCAATGGTGACAAAGAA GATGGAAGGTTTACAGCACAGCTCAATAAAGCCAGCCAGTATGT TTCTCTGCTCATCAGAGACTCCCAGCCCAGTGATTCAGCCACCTA CCTCTGTGCCGTGAACGTCCCCTTGAGTTACCAACTCACTTTCGG GAAGGGGACCAAACTCTCGGTCATACCAAATGGAGGATCTGGT GGAAGAACTGTTGCGGCGCCATCAGTGTTCATCTTTCCCCCTAG CGACGAGCAGCTGAAGAGTGGCACAGCTTCCGTGGTCTGCCTGC TGAACAATTTCTACCCCCGGGAAGCCAAGGTGCAGTGGAAAGTC GATAACGCTCTGCAGTCTGGAAATAGTCAGGAGTCAGTGACTGA ACAGGACAGCAAGGATTCCACCTATTCTCTGAGCTCCACCCTGA CACTGTCTAAAGCAGACTACGAGAAGCACAAAGTCTATGCCTGT GAAGTCACTCACCAGGGTCTGTCTTCACCAGTCACCAAATCCTT CAATAGGGGGGAATGCGGCAGTGGTGAGTTTGATGCTCCAAGCC CTCTCCCAGAGACTACAGAGAACGTGGTGTGTGCCCTGGGCCTG ACTGTGGGTCTGGTGGGCATCATTATTGGGACCATCTTCATCATC AGGAGTAAGAGGAGCAGGCTCCTGCACAGTGACTACATGAACA TGACTCCCCGCCGCCCCGGGCCCACCCGCAAGCATTACCAGCCC TATGCCCCACCACGCGACTTCGCAGCCTATCGCTCCAGAGTGAA GTTCAGCAGGAGCGCAGACGCCCCCGCGTACCAGCAGGGCCAG AACCAGCTCTATAACGAGCTCAATCTAGGACGAAGAGAGGAGT ACGATGTTTTGGACAAGAGACGTGGCCGGGACCCTGAGATGGG GGGAAAGCCGCAGAGAAGGAAGAACCCTCAGGAAGGCCTGTAC AATGAACTGCAGAAAGATAAGATGGCGGAGGCCTACAGTGAGA TTGGGATGAAAGGCGAGCGCCGGAGGGGCAAGGGGCACGATGG CCTTTACCAGGGTCTCAGTACAGCCACCAAGGACACCTACGACG CCCTTCACATGCAGGCCCTGCCCCCTCGCTGATTAATTAAGCTGC CTTCTGCGGGGCTTGCCTTCTGGCCATGCCCTTCTTCTCTCCCTTG CACCTGTACCTCTTGGTCTTTGAATAAAGCCTGAGTAGGAAGAA AAAAAAAAAAAAAAAAAAAAAGCAGGTGGCGGCCGCAGGTAA GCCAGCCCAGGCCTCGCCCTCCAGCTCAAGGCGGGACAGGTGCC CTAGAGTAGCCTGCATCCAGGGACAGGCCCCAGCCGGGTGCTGA CACGTCCACCTCCATCTCTTCCTCAGGTCTGCCCGGGTGGCATCC CTGTGACCCCTCCCCAGTGCCTCTCCTGGTCGTGGAAGGTGCTAC TCCAGTGCCCACCAGCCTTGTCCTAATAAAATTAAGTTGCATCAT TTTGTTTGACTAGGTGTCCTTGTATAATATTATGGGGTGGAGGCG GGTGGTATGGAGCAAGGGGCCCAAGTTAACTTGTTTATTGCAGC TTATAATGGTTACAAATAAAGCAATAGCATCACAAATTTCACAA ATAAAGCATTTTTTTCACTGCATTCTAGTTGTGGTTTGTCCAAAC 2025202995   29 Apr 2025 TCATCAATGTATCTTATCATGTCTGGATCCGCTTCAGGCACCGGG CTTGCGGGTCATGCACCAGGTGCGCGGTCCTTCGGGCACCTCGA CGTCGGCGGTGACGGTGAAGCCGAGCCGCTCGTAGAAGGGGAG GTTGCGGGGCGCGGAGGTCTCCAGGAAGGCGGGCACCCCGGCG CGCTCGGCCGCCTCCACTCCGGGGAGCACGACGGCGCTGCCCAG ACCCTTGCCCTGGTGGTCGGGCGAGACGCCGACGGTGGCCAGGA ACCACGCGGGCTCCTTGGGCCGGTGCGGCGCCAGGAGGCCTTCC ATCTGTTGCTGCGCGGCCAGCCTGGAACCGCTCAACTCGGCCAT GCGCGGGCCGATCTCGGCGAACACCGCCCCCGCTTCGACGCTCT CCGGCGTGGTCCAGACCGCCACCGCGGCGCCGTCGTCCGCGACC CACACCTTGCCGATGTCGAGCCCGACGCGCGTGAGGAAGAGTTC TTGCAGCTCGGTGACCCGCTCGATGTGGCGGTCCGGGTCGACGG TGTGGCGCGTGGCGGGGTAGTCGGCGAACGCGGCGGCGAGGGT GCGTACGGCCCGGGGGACGTCGTCGCGGGTGGCGAGGCGCACC GTGGGCTTGTACTCGGTCATGGTGGCCTGCAGAGTCGCTCTGTGT TCGAGGCCACACGCGTCACCTTAATATGCGAAGTGGACCTGGGA CCGCGCCGCCCCGACTGCATCTGCGTGTTTTCGCCAATGACAAG ACGCTGGGCGGGGTTTGTGTCATCATAGAACTAAAGACATGCAA ATATATTTCTTCCGGGGACACCGCCAGCAAACGCGAGCAACGGG CCACGGGGATGAAGCAGCTGCGCCACTCCCTGAAGATCCATCGT CTCCTAACAAGTTACATCACTCCTGCCCTTCCTCACCCTCATCTC CATCACCTCCTTCATCTCCGTCATCTCCGTCATCACCCTCCGCGG CAGCCCCTTCCACCATAGGTGGAAACCAGGGAGGCAAATCTACT CCATCGTCAAAGCTGCACACAGTCACCCTGATATTGCAGGTAGG AGCGGGCTTTGTCATAACAAGGTCCTTAATCGCATCCTTCAAAA CCTCAGCAAATATATGAGTTTGTAAAAAGACCATGAAATAACAG ACAATGGACTCCCTTAGCGGGCCAGGTTGTGGGCCGGGTCCAGG GGCCATTCCAAAGGGGAGACGACTCAATGGTGTAAGACGACAT TGTGGAATAGCAAGGGCAGTTCCTCGCCTTAGGTTGTAAAGGGA GGTCTTACTACCTCCATATACGAACACACCGGCGACCCAAGTTC CTTCGTCGGTAGTCCTTTCTACGTGACTCCTAGCCAGGAGAGCTC TTAAACCTTCTGCAATGTTCTCAAATTTCGGGTTGGAACCTCCTT GACCACGATGCTTTCCAAACCACCCTCCTTTTTTGCGCCTGCCTC CATCACCCTGACCCCCGCTGCGCGGGGGCACGTCAGGCTCACCA TCTGGGCCGCCTTCTTGGTGGTATTCAAAATAATCGGCTTCCCCT ACAGGGTGGAAAAATGGCCTTCTACCTGGAGGGGGCCTGCGCG GTGGAGACCCGGATGATGATGACTGACTACTGGGACTCCTGGGC CTCTTTTCTCCACGTCCACGACCTCTCCCCCTGGCTCTTTCACGA CTTCCCCCCCTGGCTCTTTCACGTCCTCTACCCCGGCGGCCTCCA CTACCTCCTCGACCCCGGCCTCCACTACCTCCTCGACCCCGGCCT CCACTGCCTCCTCGACCCCGGCCTCCACCTCCTGCTCCTGCCCCT CCCGCTCCTGCTCCTGCTCCTGTTCCACCGTGGGTCCCTTTGCAG CCAATGCAACTTGGACGTTTTTGGGGTCTCCGGACACCATCTCTA TGTCTTGGCCCTGATCCTGAGCCGCCCGGGGCTCCTGGTCTTCCG CCTCCTCGTCCTCGTCCTCTTCCCCGTCCTCGTCCATGTGCCATG ATGGCGGCCTGCAGCTGTGTTCGAGGCCGCGCGTGTCACCTTAA TATGCGAAGTGGACCTGGGACCGCGCCGCCCCGACTGCATCTGC GTGTTCGAGTTCGCCAATGACAAGACGCTGGGCGGGGAGATCCC CCTTATTAACCCTAAACGGGTAGCATATGCTTCCCGGGTAGTAG TATATACTATCCAGACTAACCCTAATTCAATAGCATATGTTACCC AACGGGAAGCATATGCTATCGAATTAGGGTTAGTAAAAGGGTCC 2025202995   29 Apr 2025 TAAGGAACAGCGATCTGGATAGCATATGCTATCCTAATCTATAT CTGGGTAGCATATGCTATCCTAATCTATATCTGGGTAGCATAGG CTATCCTAATCTATATCTGGGTAGCATATGCTATCCTAATCTATA TCTGGGTAGTATATGCTATCCTAATTTATATCTGGGTAGCATAGG CTATCCTAATCTATATCTGGGTAGCATATGCTATCCTAATCTATA TCTGGGTAGTATATGCTATCCTAATCTGTATCCGGGTAGCATATG CTATCCTCATGCATATACAGTCAGCATATGATACCCAGTAGTAG AGTGGGAGTGCTATCCTTTGCATATGCCGCCACCTCCCAAGGAG ATCTGTCGACATCGATGGGCGCGGGTGTACACTCCGCCCATCCC GCCCCTAACTCCGCCCAGTTCCGCCCATTCTCCGCCTCATGGCTG ACTAATTTTTTTTATTTATGCAGAGGCCGAGGCCGCCTCGGCCTC TGAGCTATTCCAGAAGTAGTGAGGAGGCTTTTTTGGAGGCCTAG GCTTTTGCAAAAAGCTAATTCGGCGTAATCTGCTGCTTGCAAAC AAAAAAACCACCGCTACCAGCGGTGGTTTGTTTGCCGGATCAAG AGCTACCAACTCTTTTTCCGAAGGTAACTGGCTTCAGCAGAGCG CAGATACCAAATACTGTCCTTCTAGTGTAGCCGTAGTTAGGCCA CCACTTCAAGAACTCTGTAGCACCGCCTACATACCTCGCTCTGCT GAAGCCAGTTACCAGTGGCTGCTGCCAGTGGCGATAAGTCGTGT CTTACCGGGTTGGACTCAAGAGATAGTTACCGGATAAGGCGCAG CGGTCGGGCTGAACGGGGGGTTCGTGCACACAGCCCAGCTTGGA GCGAACGACCTACACCGAACTGAGATACCTACAGCGTGAGCTAT GAGAAAGCGCCACGCTTCCCGAAGGGAGAAAGGCGGACAGGTA TCCGGTAAGCGGCAGGGTCGGAACAGGAGAGCGCACGAGGGAG CTTCCAGGGGGAAACGCCTGGTATCTTTATAGTCCTGTCGGGTTT CGCCACCTCTGACTTGAGCGTCGATTTTTGTGATGCTCGTCAGGG GGGCGGAGCCTATGGAAAAACGCCAGCAACGCAAGCTAGAGTT TAAACTTGACAGATGAGACAATAACCCTGATAAATGCTTCAATA ATATTGAAAAAGGAAAAGTATGAGTATTCAACATTTCCGTGTCG CCCTTATTCCCTTTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCA CCCAGAAACGCTGGTGAAAGTAAAAGATGCAGAAGATCACTTG GGTGCGCGAGTGGGTTACATCGAACTGGATCTCAACAGCGGTAA GATCCTTGAGAGTTTTCGCCCCGAAGAACGTTTCCCAATGATGA GCACTTTTAAAGTTCTGCTATGTGGCGCGGTATTATCCCGTATTG ATGCCGGGCAAGAGCAACTCGGTCGCCGCATACACTATTCTCAG AATGACTTGGTTGAATACTCACCAGTCACAGAAAAGCATCTTAC GGATGGCATGACAGTAAGAGAATTATGCAGTGCTGCCATAACCA TGAGTGATAACACTGCGGCCAACTTACTTCTGACAACTATCGGA GGACCGAAGGAGCTAACCGCTTTTTTGCACAACATGGGGGATCA TGTAACTCGCCTTGATCGTTGGGAACCGGAGCTGAATGAAGCCA TACCAAACGACGAGCGTGACACCACGATGCCTGTAGCAATGGC AACAACGTTGCGAAAACTATTAACTGGCGAACTACTTACTCTAG CTTCCCGGCAACAACTAATAGACTGGATGGAGGCGGATAAAGTT GCAGGACCACTTCTGCGCTCGGCACTTCCGGCTGGCTGGTTTATT GCTGATAAATCAGGAGCCGGTGAGCGTGGGTCACGCGGTATCAT TGCAGCACTGGGGCCGGATGGTAAGCCCTCCCGTATCGTAGTTA TCTACACTACGGGGAGTCAGGCAACTATGGATGAACGAAATAG ACAGATCGCTGAGATAGGTGCCTCACTGATTAAGCATTGGTAAG GATAAATTTCTGGTAAGGAGGACACGTATGGAAGTGGGCAAGTT GGGGAAGCCGTATCCGTTGCTGAATCTGGCATATGTGGGAGTAT AAGACGCGCAGCGTCGCATCAGGCATTTTTTTCTGCGCCAATGC AAAAAGGCCATCCGTCAGGATGGCCTTTCGGCATAACTAGTGAG 2025202995   29 Apr 2025 GCTCCGGTGCCCGTCAGTGGGCAGAGCGCACATCGCCCACAGTC CCCGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACCGGTGCCT AGAGAAGGTGGCGCGGGGTAAACTGGGAAAGTGATGTCGTGTA CTGGCTCCGCCTTTTTCCCGAGGGTGGGGGAGAACCGTATATAA GTGCAGTAGTCGCCGTGAACGTTCTTTTTCGCAACGGGTTTGCCG CCAGAACACAGGTAAGTGCCGTGTGTGGTTCCCGCGGGCCTGGC CTCTTTACGGGTTATGGCCCTTGCGTGCCTTGAATTACTTCCACC TGGCTGCAGTACGTGATTCTTGATCCCGAGCTTCGGGTTGGAAG TGGGTGGGAGAGTTCGAGGCCTTGCGCTTAAGGAGCCCCTTCGC CTCGTGCTTGAGTTGAGGCCTGGCCTGGGCGCTGGGGCCGCCGC GTGCGAATCTGGTGGCACCTTCGCGCCTGTCTCGCTGCTTTCGAT AAGTCTCTAGCCATTTAAAATTTTTGATGACCTGCTGCGACGCTT TTTTTCTGGCAAGATAGTCTTGTAAATGCGGGCCAAGACGATCT GCACACTGGTATTTCGGTTTTTGGGGCCGCGGGCGGCGACGGGG CCCGTGCGTCCCAGCGCACATGTTCGGCGAGGCGGGGCCTGCGA GCGCGGCCACCGAGAATCGGACGGGGGTAGTCTCAAGCTGGCC GGCCTGCTCTGGTGCCTGGCCTCGCGCCGCCGTGTATCGCCCCG CCCTGGGCGGCAAGGCTGGCCCGGTCGGCACCAGTTGCGTGAGC GGAAAGATGGCCGCTTCCCGGCCCTGCTGCAGGGAGCTCAAAAT GGAGGACGCGGCGCTCGGGAGAGCGGGCGGGTGAGTCACCCAC ACAAAGGAAAAGGGCCTTTCCGTCCTCAGCCGTCGCTTCATGTG ACTCCACGGAGTACCGGGCGCCGTCCAGGCACCTCGATTAGTTC TCGAGCTTTTGGAGTACGTCGTCTTTAGGTTGGGGGGAGGGGTT TTATGCGATGGAGTTTCCCCACACTGAGTGGGTGGAGACTGAAG TTAGGCCAGCTTGGCACTTGATGTAATTCTCCTTGGAATTTGCCC TTTTTGAGTTTGGATCTTGGTTCATTCTCAAGCCTCAGACAGTGG TTCAAAGTTTTTTTCTTCCATTTCAGGTGTCGTGAAA 9 P-NR-022 plasmid AGCTAGCTTTAATACGACTCACTATAAGGAAATAAGAGAGAAA AGAAGAGTAAGAAGAAATATAAGAGCCACCATGGGCTAGTACA GATATCTGGTGGAGCTTCTACAAAAGGGCCAAGCGTGTTCCCAC TGGCACCCAGCTCCAAGTCAACCAGCGGAGGAACAGCCGCTCTG GGATGCCTGGTGAAAGACTACTTCCCAGAGCCCGTGACCGTCTC CTGGAACTCTGGGGCCCTGACAAGCGGTGTGCACACTTTTCCTG CTGTCCTGCAGTCTAGTGGGCTGTACTCCCTGTCAAGCGTGGTCA CTGTGCCATCCTCTAGTCTGGGTACTCAGACCTATATCTGCAACG TGAATCACAAGCCTAGCAATACCAAAGTGGACAAGAAAGTCGA ACCAAAGTCCTGTGGCAGTGGTAGAGCACGGTCTGAATCTGCAC AGAGCAAGATGCTGAGTGGAGTCGGGGGCTTTGTGCTGGGCCTG CTCTTCCTTGGGGCCGGGCTGTTCATCAGGAGTAAGAGGAGCAG GCTCCTGCACAGTGACTACATGAACATGACTCCCCGCCGCCCCG GGCCCACCCGCAAGCATTACCAGCCCTATGCCCCACCACGCGAC TTCGCAGCCTATCGCTCCAGAGTGAAGTTCAGCAGGAGCGCAGA CGCCCCCGCGTACCAGCAGGGCCAGAACCAGCTCTATAACGAGC TCAATCTAGGACGAAGAGAGGAGTACGATGTTTTGGACAAGAG ACGTGGCCGGGACCCTGAGATGGGGGGAAAGCCGCAGAGAAGG AAGAACCCTCAGGAAGGCCTGTACAATGAACTGCAGAAAGATA AGATGGCGGAGGCCTACAGTGAGATTGGGATGAAAGGCGAGCG CCGGAGGGGCAAGGGGCACGATGGCCTTTACCAGGGTCTCAGT ACAGCCACCAAGGACACCTACGACGCCCTTCACATGCAGGCCCT GCCCCCTCGCTGATTAATTAAGCTGCCTTCTGCGGGGCTTGCCTT CTGGCCATGCCCTTCTTCTCTCCCTTGCACCTGTACCTCTTGGTCT 2025202995   29 Apr 2025 TTGAATAAAGCCTGAGTAGGAAGAAAAAAAAAAAAAAAAAAAA AAAGCAGGTGGCGGCCGCAGGTAAGCCAGCCCAGGCCTCGCCC TCCAGCTCAAGGCGGGACAGGTGCCCTAGAGTAGCCTGCATCCA GGGACAGGCCCCAGCCGGGTGCTGACACGTCCACCTCCATCTCT TCCTCAGGTCTGCCCGGGTGGCATCCCTGTGACCCCTCCCCAGTG CCTCTCCTGGTCGTGGAAGGTGCTACTCCAGTGCCCACCAGCCTT GTCCTAATAAAATTAAGTTGCATCATTTTGTTTGACTAGGTGTCC TTGTATAATATTATGGGGTGGAGGCGGGTGGTATGGAGCAAGGG GCCCAAGTTAACTTGTTTATTGCAGCTTATAATGGTTACAAATAA AGCAATAGCATCACAAATTTCACAAATAAAGCATTTTTTTCACT GCATTCTAGTTGTGGTTTGTCCAAACTCATCAATGTATCTTATCA TGTCTGGATCCGCTTCAGGCACCGGGCTTGCGGGTCATGCACCA GGTGCGCGGTCCTTCGGGCACCTCGACGTCGGCGGTGACGGTGA AGCCGAGCCGCTCGTAGAAGGGGAGGTTGCGGGGCGCGGAGGT CTCCAGGAAGGCGGGCACCCCGGCGCGCTCGGCCGCCTCCACTC CGGGGAGCACGACGGCGCTGCCCAGACCCTTGCCCTGGTGGTCG GGCGAGACGCCGACGGTGGCCAGGAACCACGCGGGCTCCTTGG GCCGGTGCGGCGCCAGGAGGCCTTCCATCTGTTGCTGCGCGGCC AGCCTGGAACCGCTCAACTCGGCCATGCGCGGGCCGATCTCGGC GAACACCGCCCCCGCTTCGACGCTCTCCGGCGTGGTCCAGACCG CCACCGCGGCGCCGTCGTCCGCGACCCACACCTTGCCGATGTCG AGCCCGACGCGCGTGAGGAAGAGTTCTTGCAGCTCGGTGACCCG CTCGATGTGGCGGTCCGGGTCGACGGTGTGGCGCGTGGCGGGGT AGTCGGCGAACGCGGCGGCGAGGGTGCGTACGGCCCGGGGGAC GTCGTCGCGGGTGGCGAGGCGCACCGTGGGCTTGTACTCGGTCA TGGTGGCCTGCAGAGTCGCTCTGTGTTCGAGGCCACACGCGTCA CCTTAATATGCGAAGTGGACCTGGGACCGCGCCGCCCCGACTGC ATCTGCGTGTTTTCGCCAATGACAAGACGCTGGGCGGGGTTTGT GTCATCATAGAACTAAAGACATGCAAATATATTTCTTCCGGGGA CACCGCCAGCAAACGCGAGCAACGGGCCACGGGGATGAAGCAG CTGCGCCACTCCCTGAAGATCCATCGTCTCCTAACAAGTTACATC ACTCCTGCCCTTCCTCACCCTCATCTCCATCACCTCCTTCATCTCC GTCATCTCCGTCATCACCCTCCGCGGCAGCCCCTTCCACCATAGG TGGAAACCAGGGAGGCAAATCTACTCCATCGTCAAAGCTGCACA CAGTCACCCTGATATTGCAGGTAGGAGCGGGCTTTGTCATAACA AGGTCCTTAATCGCATCCTTCAAAACCTCAGCAAATATATGAGT TTGTAAAAAGACCATGAAATAACAGACAATGGACTCCCTTAGCG GGCCAGGTTGTGGGCCGGGTCCAGGGGCCATTCCAAAGGGGAG ACGACTCAATGGTGTAAGACGACATTGTGGAATAGCAAGGGCA GTTCCTCGCCTTAGGTTGTAAAGGGAGGTCTTACTACCTCCATAT ACGAACACACCGGCGACCCAAGTTCCTTCGTCGGTAGTCCTTTC TACGTGACTCCTAGCCAGGAGAGCTCTTAAACCTTCTGCAATGT TCTCAAATTTCGGGTTGGAACCTCCTTGACCACGATGCTTTCCAA ACCACCCTCCTTTTTTGCGCCTGCCTCCATCACCCTGACCCCCGC TGCGCGGGGGCACGTCAGGCTCACCATCTGGGCCGCCTTCTTGG TGGTATTCAAAATAATCGGCTTCCCCTACAGGGTGGAAAAATGG CCTTCTACCTGGAGGGGGCCTGCGCGGTGGAGACCCGGATGATG ATGACTGACTACTGGGACTCCTGGGCCTCTTTTCTCCACGTCCAC GACCTCTCCCCCTGGCTCTTTCACGACTTCCCCCCCTGGCTCTTT CACGTCCTCTACCCCGGCGGCCTCCACTACCTCCTCGACCCCGGC CTCCACTACCTCCTCGACCCCGGCCTCCACTGCCTCCTCGACCCC 2025202995   29 Apr 2025 GGCCTCCACCTCCTGCTCCTGCCCCTCCCGCTCCTGCTCCTGCTC CTGTTCCACCGTGGGTCCCTTTGCAGCCAATGCAACTTGGACGTT TTTGGGGTCTCCGGACACCATCTCTATGTCTTGGCCCTGATCCTG AGCCGCCCGGGGCTCCTGGTCTTCCGCCTCCTCGTCCTCGTCCTC TTCCCCGTCCTCGTCCATGTGCCATGATGGCGGCCTGCAGCTGTG TTCGAGGCCGCGCGTGTCACCTTAATATGCGAAGTGGACCTGGG ACCGCGCCGCCCCGACTGCATCTGCGTGTTCGAGTTCGCCAATG ACAAGACGCTGGGCGGGGAGATCCCCCTTATTAACCCTAAACGG GTAGCATATGCTTCCCGGGTAGTAGTATATACTATCCAGACTAA CCCTAATTCAATAGCATATGTTACCCAACGGGAAGCATATGCTA TCGAATTAGGGTTAGTAAAAGGGTCCTAAGGAACAGCGATCTGG ATAGCATATGCTATCCTAATCTATATCTGGGTAGCATATGCTATC CTAATCTATATCTGGGTAGCATAGGCTATCCTAATCTATATCTGG GTAGCATATGCTATCCTAATCTATATCTGGGTAGTATATGCTATC CTAATTTATATCTGGGTAGCATAGGCTATCCTAATCTATATCTGG GTAGCATATGCTATCCTAATCTATATCTGGGTAGTATATGCTATC CTAATCTGTATCCGGGTAGCATATGCTATCCTCATGCATATACAG TCAGCATATGATACCCAGTAGTAGAGTGGGAGTGCTATCCTTTG CATATGCCGCCACCTCCCAAGGAGATCTGTCGACATCGATGGGC GCGGGTGTACACTCCGCCCATCCCGCCCCTAACTCCGCCCAGTT CCGCCCATTCTCCGCCTCATGGCTGACTAATTTTTTTTATTTATGC AGAGGCCGAGGCCGCCTCGGCCTCTGAGCTATTCCAGAAGTAGT GAGGAGGCTTTTTTGGAGGCCTAGGCTTTTGCAAAAAGCTAATT CGGCGTAATCTGCTGCTTGCAAACAAAAAAACCACCGCTACCAG CGGTGGTTTGTTTGCCGGATCAAGAGCTACCAACTCTTTTTCCGA AGGTAACTGGCTTCAGCAGAGCGCAGATACCAAATACTGTCCTT CTAGTGTAGCCGTAGTTAGGCCACCACTTCAAGAACTCTGTAGC ACCGCCTACATACCTCGCTCTGCTGAAGCCAGTTACCAGTGGCT GCTGCCAGTGGCGATAAGTCGTGTCTTACCGGGTTGGACTCAAG AGATAGTTACCGGATAAGGCGCAGCGGTCGGGCTGAACGGGGG GTTCGTGCACACAGCCCAGCTTGGAGCGAACGACCTACACCGAA CTGAGATACCTACAGCGTGAGCTATGAGAAAGCGCCACGCTTCC CGAAGGGAGAAAGGCGGACAGGTATCCGGTAAGCGGCAGGGTC GGAACAGGAGAGCGCACGAGGGAGCTTCCAGGGGGAAACGCCT GGTATCTTTATAGTCCTGTCGGGTTTCGCCACCTCTGACTTGAGC GTCGATTTTTGTGATGCTCGTCAGGGGGGCGGAGCCTATGGAAA AACGCCAGCAACGCAAGCTAGAGTTTAAACTTGACAGATGAGA CAATAACCCTGATAAATGCTTCAATAATATTGAAAAAGGAAAAG TATGAGTATTCAACATTTCCGTGTCGCCCTTATTCCCTTTTTTGCG GCATTTTGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGTGAAA GTAAAAGATGCAGAAGATCACTTGGGTGCGCGAGTGGGTTACAT CGAACTGGATCTCAACAGCGGTAAGATCCTTGAGAGTTTTCGCC CCGAAGAACGTTTCCCAATGATGAGCACTTTTAAAGTTCTGCTAT GTGGCGCGGTATTATCCCGTATTGATGCCGGGCAAGAGCAACTC GGTCGCCGCATACACTATTCTCAGAATGACTTGGTTGAATACTC ACCAGTCACAGAAAAGCATCTTACGGATGGCATGACAGTAAGA GAATTATGCAGTGCTGCCATAACCATGAGTGATAACACTGCGGC CAACTTACTTCTGACAACTATCGGAGGACCGAAGGAGCTAACCG CTTTTTTGCACAACATGGGGGATCATGTAACTCGCCTTGATCGTT GGGAACCGGAGCTGAATGAAGCCATACCAAACGACGAGCGTGA CACCACGATGCCTGTAGCAATGGCAACAACGTTGCGAAAACTAT 2025202995   29 Apr 2025 TAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAACTAATA GACTGGATGGAGGCGGATAAAGTTGCAGGACCACTTCTGCGCTC GGCACTTCCGGCTGGCTGGTTTATTGCTGATAAATCAGGAGCCG GTGAGCGTGGGTCACGCGGTATCATTGCAGCACTGGGGCCGGAT GGTAAGCCCTCCCGTATCGTAGTTATCTACACTACGGGGAGTCA GGCAACTATGGATGAACGAAATAGACAGATCGCTGAGATAGGT GCCTCACTGATTAAGCATTGGTAAGGATAAATTTCTGGTAAGGA GGACACGTATGGAAGTGGGCAAGTTGGGGAAGCCGTATCCGTTG CTGAATCTGGCATATGTGGGAGTATAAGACGCGCAGCGTCGCAT CAGGCATTTTTTTCTGCGCCAATGCAAAAAGGCCATCCGTCAGG ATGGCCTTTCGGCATAACTAGTGAGGCTCCGGTGCCCGTCAGTG GGCAGAGCGCACATCGCCCACAGTCCCCGAGAAGTTGGGGGGA GGGGTCGGCAATTGAACCGGTGCCTAGAGAAGGTGGCGCGGGG TAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCTTTTTCCCG AGGGTGGGGGAGAACCGTATATAAGTGCAGTAGTCGCCGTGAA CGTTCTTTTTCGCAACGGGTTTGCCGCCAGAACACAGGTAAGTG CCGTGTGTGGTTCCCGCGGGCCTGGCCTCTTTACGGGTTATGGCC CTTGCGTGCCTTGAATTACTTCCACCTGGCTGCAGTACGTGATTC TTGATCCCGAGCTTCGGGTTGGAAGTGGGTGGGAGAGTTCGAGG CCTTGCGCTTAAGGAGCCCCTTCGCCTCGTGCTTGAGTTGAGGCC TGGCCTGGGCGCTGGGGCCGCCGCGTGCGAATCTGGTGGCACCT TCGCGCCTGTCTCGCTGCTTTCGATAAGTCTCTAGCCATTTAAAA TTTTTGATGACCTGCTGCGACGCTTTTTTTCTGGCAAGATAGTCT TGTAAATGCGGGCCAAGACGATCTGCACACTGGTATTTCGGTTT TTGGGGCCGCGGGCGGCGACGGGGCCCGTGCGTCCCAGCGCAC ATGTTCGGCGAGGCGGGGCCTGCGAGCGCGGCCACCGAGAATC GGACGGGGGTAGTCTCAAGCTGGCCGGCCTGCTCTGGTGCCTGG CCTCGCGCCGCCGTGTATCGCCCCGCCCTGGGCGGCAAGGCTGG CCCGGTCGGCACCAGTTGCGTGAGCGGAAAGATGGCCGCTTCCC GGCCCTGCTGCAGGGAGCTCAAAATGGAGGACGCGGCGCTCGG GAGAGCGGGCGGGTGAGTCACCCACACAAAGGAAAAGGGCCTT TCCGTCCTCAGCCGTCGCTTCATGTGACTCCACGGAGTACCGGG CGCCGTCCAGGCACCTCGATTAGTTCTCGAGCTTTTGGAGTACGT CGTCTTTAGGTTGGGGGGAGGGGTTTTATGCGATGGAGTTTCCC CACACTGAGTGGGTGGAGACTGAAGTTAGGCCAGCTTGGCACTT GATGTAATTCTCCTTGGAATTTGCCCTTTTTGAGTTTGGATCTTG GTTCATTCTCAAGCCTCAGACAGTGGTTCAAAGTTTTTTTCTTCC ATTTCAGGTGTCGTGAAA 10 P-NR-026 plasmid AGCTAGCTTTAATACGACTCACTATAAGGAAATAAGAGAGAAA AGAAGAGTAAGAAGAAATATAAGAGCCACCATGCTGAGTCTTCT GCTCCTTCTCCTGGGACTAGGCTCTGTGTTCAGTGCTGTCATCTC TCAAAAGCCAAGCAGGGATATCTGTCAACGTGGAACCTCCCTGA CGATCCAGTGTCAAGTCGATAGCCAAGTCACCATGATGTTCTGG TACCGTCAGCAACCTGGACAGAGCCTGACACTGATCGCAACTGC AAATCAGGGCTCTGAGGCCACATATGAGAGTGGATTTGTCATTG ACAAGTTTCCCATCAGCCGCCCAAACCTAACATTCTCAACTCTG ACTGTGAGCAACATGAGCCCTGAAGACAGCAGCATATATCTCTG CAGCGTTGCCGGGACTATCGACGAGCAGTACTTCGGGCCGGGCA CCAGGCTCACGGTCACAGAGGGAGGATCTGGTGGAGCTTCTACA AAAGGGCCAAGCGTGTTCCCACTGGCACCCAGCTCCAAGTCAAC CAGCGGAGGAACAGCCGCTCTGGGATGCCTGGTGAAAGACTAC 2025202995   29 Apr 2025 TTCCCAGAGCCCGTGACCGTCTCCTGGAACTCTGGGGCCCTGAC AAGCGGTGTGCACACTTTTCCTGCTGTCCTGCAGTCTAGTGGGCT GTACTCCCTGTCAAGCGTGGTCACTGTGCCATCCTCTAGTCTGGG TACTCAGACCTATATCTGCAACGTGAATCACAAGCCTAGCAATA CCAAAGTGGACAAGAAAGTCGAACCAAAGTCCTGTGGCAGTGG TAGAGCACGGTCTGAATCTGCACAGAGCAAGATGCTGAGTGGA GTCGGGGGCTTTGTGCTGGGCCTGCTCTTCCTTGGGGCCGGGCT GTTCATCAGGAGTAAGAGGAGCAGGCTCCTGCACAGTGACTACA TGAACATGACTCCCCGCCGCCCCGGGCCCACCCGCAAGCATTAC CAGCCCTATGCCCCACCACGCGACTTCGCAGCCTATCGCTCCAG AGTGAAGTTCAGCAGGAGCGCAGACGCCCCCGCGTACCAGCAG GGCCAGAACCAGCTCTATAACGAGCTCAATCTAGGACGAAGAG AGGAGTACGATGTTTTGGACAAGAGACGTGGCCGGGACCCTGA GATGGGGGGAAAGCCGCAGAGAAGGAAGAACCCTCAGGAAGG CCTGTACAATGAACTGCAGAAAGATAAGATGGCGGAGGCCTAC AGTGAGATTGGGATGAAAGGCGAGCGCCGGAGGGGCAAGGGGC ACGATGGCCTTTACCAGGGTCTCAGTACAGCCACCAAGGACACC TACGACGCCCTTCACATGCAGGCCCTGCCCCCTCGCTGATTAATT AAGCTGCCTTCTGCGGGGCTTGCCTTCTGGCCATGCCCTTCTTCT CTCCCTTGCACCTGTACCTCTTGGTCTTTGAATAAAGCCTGAGTA GGAAGAAAAAAAAAAAAAAAAAAAAAAAGCAGGTGGCGGCCG CAGGTAAGCCAGCCCAGGCCTCGCCCTCCAGCTCAAGGCGGGAC AGGTGCCCTAGAGTAGCCTGCATCCAGGGACAGGCCCCAGCCG GGTGCTGACACGTCCACCTCCATCTCTTCCTCAGGTCTGCCCGGG TGGCATCCCTGTGACCCCTCCCCAGTGCCTCTCCTGGTCGTGGAA GGTGCTACTCCAGTGCCCACCAGCCTTGTCCTAATAAAATTAAG TTGCATCATTTTGTTTGACTAGGTGTCCTTGTATAATATTATGGG GTGGAGGCGGGTGGTATGGAGCAAGGGGCCCAAGTTAACTTGTT TATTGCAGCTTATAATGGTTACAAATAAAGCAATAGCATCACAA ATTTCACAAATAAAGCATTTTTTTCACTGCATTCTAGTTGTGGTT TGTCCAAACTCATCAATGTATCTTATCATGTCTGGATCCGCTTCA GGCACCGGGCTTGCGGGTCATGCACCAGGTGCGCGGTCCTTCGG GCACCTCGACGTCGGCGGTGACGGTGAAGCCGAGCCGCTCGTAG AAGGGGAGGTTGCGGGGCGCGGAGGTCTCCAGGAAGGCGGGCA CCCCGGCGCGCTCGGCCGCCTCCACTCCGGGGAGCACGACGGCG CTGCCCAGACCCTTGCCCTGGTGGTCGGGCGAGACGCCGACGGT GGCCAGGAACCACGCGGGCTCCTTGGGCCGGTGCGGCGCCAGG AGGCCTTCCATCTGTTGCTGCGCGGCCAGCCTGGAACCGCTCAA CTCGGCCATGCGCGGGCCGATCTCGGCGAACACCGCCCCCGCTT CGACGCTCTCCGGCGTGGTCCAGACCGCCACCGCGGCGCCGTCG TCCGCGACCCACACCTTGCCGATGTCGAGCCCGACGCGCGTGAG GAAGAGTTCTTGCAGCTCGGTGACCCGCTCGATGTGGCGGTCCG GGTCGACGGTGTGGCGCGTGGCGGGGTAGTCGGCGAACGCGGC GGCGAGGGTGCGTACGGCCCGGGGGACGTCGTCGCGGGTGGCG AGGCGCACCGTGGGCTTGTACTCGGTCATGGTGGCCTGCAGAGT CGCTCTGTGTTCGAGGCCACACGCGTCACCTTAATATGCGAAGT GGACCTGGGACCGCGCCGCCCCGACTGCATCTGCGTGTTTTCGC CAATGACAAGACGCTGGGCGGGGTTTGTGTCATCATAGAACTAA AGACATGCAAATATATTTCTTCCGGGGACACCGCCAGCAAACGC GAGCAACGGGCCACGGGGATGAAGCAGCTGCGCCACTCCCTGA AGATCCATCGTCTCCTAACAAGTTACATCACTCCTGCCCTTCCTC 2025202995   29 Apr 2025 ACCCTCATCTCCATCACCTCCTTCATCTCCGTCATCTCCGTCATC ACCCTCCGCGGCAGCCCCTTCCACCATAGGTGGAAACCAGGGAG GCAAATCTACTCCATCGTCAAAGCTGCACACAGTCACCCTGATA TTGCAGGTAGGAGCGGGCTTTGTCATAACAAGGTCCTTAATCGC ATCCTTCAAAACCTCAGCAAATATATGAGTTTGTAAAAAGACCA TGAAATAACAGACAATGGACTCCCTTAGCGGGCCAGGTTGTGGG CCGGGTCCAGGGGCCATTCCAAAGGGGAGACGACTCAATGGTG TAAGACGACATTGTGGAATAGCAAGGGCAGTTCCTCGCCTTAGG TTGTAAAGGGAGGTCTTACTACCTCCATATACGAACACACCGGC GACCCAAGTTCCTTCGTCGGTAGTCCTTTCTACGTGACTCCTAGC CAGGAGAGCTCTTAAACCTTCTGCAATGTTCTCAAATTTCGGGTT GGAACCTCCTTGACCACGATGCTTTCCAAACCACCCTCCTTTTTT GCGCCTGCCTCCATCACCCTGACCCCCGCTGCGCGGGGGCACGT CAGGCTCACCATCTGGGCCGCCTTCTTGGTGGTATTCAAAATAA TCGGCTTCCCCTACAGGGTGGAAAAATGGCCTTCTACCTGGAGG GGGCCTGCGCGGTGGAGACCCGGATGATGATGACTGACTACTGG GACTCCTGGGCCTCTTTTCTCCACGTCCACGACCTCTCCCCCTGG CTCTTTCACGACTTCCCCCCCTGGCTCTTTCACGTCCTCTACCCC GGCGGCCTCCACTACCTCCTCGACCCCGGCCTCCACTACCTCCTC GACCCCGGCCTCCACTGCCTCCTCGACCCCGGCCTCCACCTCCTG CTCCTGCCCCTCCCGCTCCTGCTCCTGCTCCTGTTCCACCGTGGG TCCCTTTGCAGCCAATGCAACTTGGACGTTTTTGGGGTCTCCGGA CACCATCTCTATGTCTTGGCCCTGATCCTGAGCCGCCCGGGGCTC CTGGTCTTCCGCCTCCTCGTCCTCGTCCTCTTCCCCGTCCTCGTCC ATGTGCCATGATGGCGGCCTGCAGCTGTGTTCGAGGCCGCGCGT GTCACCTTAATATGCGAAGTGGACCTGGGACCGCGCCGCCCCGA CTGCATCTGCGTGTTCGAGTTCGCCAATGACAAGACGCTGGGCG GGGAGATCCCCCTTATTAACCCTAAACGGGTAGCATATGCTTCC CGGGTAGTAGTATATACTATCCAGACTAACCCTAATTCAATAGC ATATGTTACCCAACGGGAAGCATATGCTATCGAATTAGGGTTAG TAAAAGGGTCCTAAGGAACAGCGATCTGGATAGCATATGCTATC CTAATCTATATCTGGGTAGCATATGCTATCCTAATCTATATCTGG GTAGCATAGGCTATCCTAATCTATATCTGGGTAGCATATGCTATC CTAATCTATATCTGGGTAGTATATGCTATCCTAATTTATATCTGG GTAGCATAGGCTATCCTAATCTATATCTGGGTAGCATATGCTATC CTAATCTATATCTGGGTAGTATATGCTATCCTAATCTGTATCCGG GTAGCATATGCTATCCTCATGCATATACAGTCAGCATATGATAC CCAGTAGTAGAGTGGGAGTGCTATCCTTTGCATATGCCGCCACC TCCCAAGGAGATCTGTCGACATCGATGGGCGCGGGTGTACACTC CGCCCATCCCGCCCCTAACTCCGCCCAGTTCCGCCCATTCTCCGC CTCATGGCTGACTAATTTTTTTTATTTATGCAGAGGCCGAGGCCG CCTCGGCCTCTGAGCTATTCCAGAAGTAGTGAGGAGGCTTTTTTG GAGGCCTAGGCTTTTGCAAAAAGCTAATTCGGCGTAATCTGCTG CTTGCAAACAAAAAAACCACCGCTACCAGCGGTGGTTTGTTTGC CGGATCAAGAGCTACCAACTCTTTTTCCGAAGGTAACTGGCTTC AGCAGAGCGCAGATACCAAATACTGTCCTTCTAGTGTAGCCGTA GTTAGGCCACCACTTCAAGAACTCTGTAGCACCGCCTACATACC TCGCTCTGCTGAAGCCAGTTACCAGTGGCTGCTGCCAGTGGCGA TAAGTCGTGTCTTACCGGGTTGGACTCAAGAGATAGTTACCGGA TAAGGCGCAGCGGTCGGGCTGAACGGGGGGTTCGTGCACACAG CCCAGCTTGGAGCGAACGACCTACACCGAACTGAGATACCTACA 2025202995   29 Apr 2025 GCGTGAGCTATGAGAAAGCGCCACGCTTCCCGAAGGGAGAAAG GCGGACAGGTATCCGGTAAGCGGCAGGGTCGGAACAGGAGAGC GCACGAGGGAGCTTCCAGGGGGAAACGCCTGGTATCTTTATAGT CCTGTCGGGTTTCGCCACCTCTGACTTGAGCGTCGATTTTTGTGA TGCTCGTCAGGGGGGCGGAGCCTATGGAAAAACGCCAGCAACG CAAGCTAGAGTTTAAACTTGACAGATGAGACAATAACCCTGATA AATGCTTCAATAATATTGAAAAAGGAAAAGTATGAGTATTCAAC ATTTCCGTGTCGCCCTTATTCCCTTTTTTGCGGCATTTTGCCTTCC TGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTAAAAGATGCAG AAGATCACTTGGGTGCGCGAGTGGGTTACATCGAACTGGATCTC AACAGCGGTAAGATCCTTGAGAGTTTTCGCCCCGAAGAACGTTT CCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTATT ATCCCGTATTGATGCCGGGCAAGAGCAACTCGGTCGCCGCATAC ACTATTCTCAGAATGACTTGGTTGAATACTCACCAGTCACAGAA AAGCATCTTACGGATGGCATGACAGTAAGAGAATTATGCAGTGC TGCCATAACCATGAGTGATAACACTGCGGCCAACTTACTTCTGA CAACTATCGGAGGACCGAAGGAGCTAACCGCTTTTTTGCACAAC ATGGGGGATCATGTAACTCGCCTTGATCGTTGGGAACCGGAGCT GAATGAAGCCATACCAAACGACGAGCGTGACACCACGATGCCT GTAGCAATGGCAACAACGTTGCGAAAACTATTAACTGGCGAACT ACTTACTCTAGCTTCCCGGCAACAACTAATAGACTGGATGGAGG CGGATAAAGTTGCAGGACCACTTCTGCGCTCGGCACTTCCGGCT GGCTGGTTTATTGCTGATAAATCAGGAGCCGGTGAGCGTGGGTC ACGCGGTATCATTGCAGCACTGGGGCCGGATGGTAAGCCCTCCC GTATCGTAGTTATCTACACTACGGGGAGTCAGGCAACTATGGAT GAACGAAATAGACAGATCGCTGAGATAGGTGCCTCACTGATTAA GCATTGGTAAGGATAAATTTCTGGTAAGGAGGACACGTATGGAA GTGGGCAAGTTGGGGAAGCCGTATCCGTTGCTGAATCTGGCATA TGTGGGAGTATAAGACGCGCAGCGTCGCATCAGGCATTTTTTTC TGCGCCAATGCAAAAAGGCCATCCGTCAGGATGGCCTTTCGGCA TAACTAGTGAGGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACAT CGCCCACAGTCCCCGAGAAGTTGGGGGGAGGGGTCGGCAATTG AACCGGTGCCTAGAGAAGGTGGCGCGGGGTAAACTGGGAAAGT GATGTCGTGTACTGGCTCCGCCTTTTTCCCGAGGGTGGGGGAGA ACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTCTTTTTCGCAA CGGGTTTGCCGCCAGAACACAGGTAAGTGCCGTGTGTGGTTCCC GCGGGCCTGGCCTCTTTACGGGTTATGGCCCTTGCGTGCCTTGAA TTACTTCCACCTGGCTGCAGTACGTGATTCTTGATCCCGAGCTTC GGGTTGGAAGTGGGTGGGAGAGTTCGAGGCCTTGCGCTTAAGGA GCCCCTTCGCCTCGTGCTTGAGTTGAGGCCTGGCCTGGGCGCTG GGGCCGCCGCGTGCGAATCTGGTGGCACCTTCGCGCCTGTCTCG CTGCTTTCGATAAGTCTCTAGCCATTTAAAATTTTTGATGACCTG CTGCGACGCTTTTTTTCTGGCAAGATAGTCTTGTAAATGCGGGCC AAGACGATCTGCACACTGGTATTTCGGTTTTTGGGGCCGCGGGC GGCGACGGGGCCCGTGCGTCCCAGCGCACATGTTCGGCGAGGC GGGGCCTGCGAGCGCGGCCACCGAGAATCGGACGGGGGTAGTC TCAAGCTGGCCGGCCTGCTCTGGTGCCTGGCCTCGCGCCGCCGT GTATCGCCCCGCCCTGGGCGGCAAGGCTGGCCCGGTCGGCACCA GTTGCGTGAGCGGAAAGATGGCCGCTTCCCGGCCCTGCTGCAGG GAGCTCAAAATGGAGGACGCGGCGCTCGGGAGAGCGGGCGGGT GAGTCACCCACACAAAGGAAAAGGGCCTTTCCGTCCTCAGCCGT 2025202995   29 Apr 2025 CGCTTCATGTGACTCCACGGAGTACCGGGCGCCGTCCAGGCACC TCGATTAGTTCTCGAGCTTTTGGAGTACGTCGTCTTTAGGTTGGG GGGAGGGGTTTTATGCGATGGAGTTTCCCCACACTGAGTGGGTG GAGACTGAAGTTAGGCCAGCTTGGCACTTGATGTAATTCTCCTT GGAATTTGCCCTTTTTGAGTTTGGATCTTGGTTCATTCTCAAGCC TCAGACAGTGGTTCAAAGTTTTTTTCTTCCATTTCAGGTGTCGTG AAA 11 P-NR-023 plasmid AGCTAGCTTTAATACGACTCACTATAAGGAAATAAGAGAGAAA AGAAGAGTAAGAAGAAATATAAGAGCCACCATGGGCTAGTACA GATATCTAGTACAGGTAGCTCCACTGGGCCGGGTAGCACATCAG TTGATGAGTTGCAGGCCGAGGTGGACCAGCTTCAAGATGAGAAC TACGCTCTGAAAACGAAAGTAGCACAGTTGCGAAAAAAGGTAG AGAAGCTCGCGTCTGGTGGATGTGGTGGAGAGTTTGATGCTCCA AGCCCTCTCCCAGAGACTACAGAGAACGTGGTGTGTGCCCTGGG CCTGACTGTGGGTCTGGTGGGCATCATTATTGGGACCATCTTCAT CATCAGGAGTAAGAGGAGCAGGCTCCTGCACAGTGACTACATG AACATGACTCCCCGCCGCCCCGGGCCCACCCGCAAGCATTACCA GCCCTATGCCCCACCACGCGACTTCGCAGCCTATCGCTCCAGAG TGAAGTTCAGCAGGAGCGCAGACGCCCCCGCGTACCAGCAGGG CCAGAACCAGCTCTATAACGAGCTCAATCTAGGACGAAGAGAG GAGTACGATGTTTTGGACAAGAGACGTGGCCGGGACCCTGAGAT GGGGGGAAAGCCGCAGAGAAGGAAGAACCCTCAGGAAGGCCTG TACAATGAACTGCAGAAAGATAAGATGGCGGAGGCCTACAGTG AGATTGGGATGAAAGGCGAGCGCCGGAGGGGCAAGGGGCACGA TGGCCTTTACCAGGGTCTCAGTACAGCCACCAAGGACACCTACG ACGCCCTTCACATGCAGGCCCTGCCCCCTCGCTGATTAATTAAG CTGCCTTCTGCGGGGCTTGCCTTCTGGCCATGCCCTTCTTCTCTC CCTTGCACCTGTACCTCTTGGTCTTTGAATAAAGCCTGAGTAGGA AGAAAAAAAAAAAAAAAAAAAAAAAGCAGGTGGCGGCCGCAG GTAAGCCAGCCCAGGCCTCGCCCTCCAGCTCAAGGCGGGACAG GTGCCCTAGAGTAGCCTGCATCCAGGGACAGGCCCCAGCCGGGT GCTGACACGTCCACCTCCATCTCTTCCTCAGGTCTGCCCGGGTGG CATCCCTGTGACCCCTCCCCAGTGCCTCTCCTGGTCGTGGAAGGT GCTACTCCAGTGCCCACCAGCCTTGTCCTAATAAAATTAAGTTG CATCATTTTGTTTGACTAGGTGTCCTTGTATAATATTATGGGGTG GAGGCGGGTGGTATGGAGCAAGGGGCCCAAGTTAACTTGTTTAT TGCAGCTTATAATGGTTACAAATAAAGCAATAGCATCACAAATT TCACAAATAAAGCATTTTTTTCACTGCATTCTAGTTGTGGTTTGT CCAAACTCATCAATGTATCTTATCATGTCTGGATCCGCTTCAGGC ACCGGGCTTGCGGGTCATGCACCAGGTGCGCGGTCCTTCGGGCA CCTCGACGTCGGCGGTGACGGTGAAGCCGAGCCGCTCGTAGAA GGGGAGGTTGCGGGGCGCGGAGGTCTCCAGGAAGGCGGGCACC CCGGCGCGCTCGGCCGCCTCCACTCCGGGGAGCACGACGGCGCT GCCCAGACCCTTGCCCTGGTGGTCGGGCGAGACGCCGACGGTGG CCAGGAACCACGCGGGCTCCTTGGGCCGGTGCGGCGCCAGGAG GCCTTCCATCTGTTGCTGCGCGGCCAGCCTGGAACCGCTCAACT CGGCCATGCGCGGGCCGATCTCGGCGAACACCGCCCCCGCTTCG ACGCTCTCCGGCGTGGTCCAGACCGCCACCGCGGCGCCGTCGTC CGCGACCCACACCTTGCCGATGTCGAGCCCGACGCGCGTGAGGA AGAGTTCTTGCAGCTCGGTGACCCGCTCGATGTGGCGGTCCGGG TCGACGGTGTGGCGCGTGGCGGGGTAGTCGGCGAACGCGGCGG 2025202995   29 Apr 2025 CGAGGGTGCGTACGGCCCGGGGGACGTCGTCGCGGGTGGCGAG GCGCACCGTGGGCTTGTACTCGGTCATGGTGGCCTGCAGAGTCG CTCTGTGTTCGAGGCCACACGCGTCACCTTAATATGCGAAGTGG ACCTGGGACCGCGCCGCCCCGACTGCATCTGCGTGTTTTCGCCA ATGACAAGACGCTGGGCGGGGTTTGTGTCATCATAGAACTAAAG ACATGCAAATATATTTCTTCCGGGGACACCGCCAGCAAACGCGA GCAACGGGCCACGGGGATGAAGCAGCTGCGCCACTCCCTGAAG ATCCATCGTCTCCTAACAAGTTACATCACTCCTGCCCTTCCTCAC CCTCATCTCCATCACCTCCTTCATCTCCGTCATCTCCGTCATCAC CCTCCGCGGCAGCCCCTTCCACCATAGGTGGAAACCAGGGAGGC AAATCTACTCCATCGTCAAAGCTGCACACAGTCACCCTGATATT GCAGGTAGGAGCGGGCTTTGTCATAACAAGGTCCTTAATCGCAT CCTTCAAAACCTCAGCAAATATATGAGTTTGTAAAAAGACCATG AAATAACAGACAATGGACTCCCTTAGCGGGCCAGGTTGTGGGCC GGGTCCAGGGGCCATTCCAAAGGGGAGACGACTCAATGGTGTA AGACGACATTGTGGAATAGCAAGGGCAGTTCCTCGCCTTAGGTT GTAAAGGGAGGTCTTACTACCTCCATATACGAACACACCGGCGA CCCAAGTTCCTTCGTCGGTAGTCCTTTCTACGTGACTCCTAGCCA GGAGAGCTCTTAAACCTTCTGCAATGTTCTCAAATTTCGGGTTGG AACCTCCTTGACCACGATGCTTTCCAAACCACCCTCCTTTTTTGC GCCTGCCTCCATCACCCTGACCCCCGCTGCGCGGGGGCACGTCA GGCTCACCATCTGGGCCGCCTTCTTGGTGGTATTCAAAATAATC GGCTTCCCCTACAGGGTGGAAAAATGGCCTTCTACCTGGAGGGG GCCTGCGCGGTGGAGACCCGGATGATGATGACTGACTACTGGGA CTCCTGGGCCTCTTTTCTCCACGTCCACGACCTCTCCCCCTGGCT CTTTCACGACTTCCCCCCCTGGCTCTTTCACGTCCTCTACCCCGG CGGCCTCCACTACCTCCTCGACCCCGGCCTCCACTACCTCCTCGA CCCCGGCCTCCACTGCCTCCTCGACCCCGGCCTCCACCTCCTGCT CCTGCCCCTCCCGCTCCTGCTCCTGCTCCTGTTCCACCGTGGGTC CCTTTGCAGCCAATGCAACTTGGACGTTTTTGGGGTCTCCGGAC ACCATCTCTATGTCTTGGCCCTGATCCTGAGCCGCCCGGGGCTCC TGGTCTTCCGCCTCCTCGTCCTCGTCCTCTTCCCCGTCCTCGTCCA TGTGCCATGATGGCGGCCTGCAGCTGTGTTCGAGGCCGCGCGTG TCACCTTAATATGCGAAGTGGACCTGGGACCGCGCCGCCCCGAC TGCATCTGCGTGTTCGAGTTCGCCAATGACAAGACGCTGGGCGG GGAGATCCCCCTTATTAACCCTAAACGGGTAGCATATGCTTCCC GGGTAGTAGTATATACTATCCAGACTAACCCTAATTCAATAGCA TATGTTACCCAACGGGAAGCATATGCTATCGAATTAGGGTTAGT AAAAGGGTCCTAAGGAACAGCGATCTGGATAGCATATGCTATCC TAATCTATATCTGGGTAGCATATGCTATCCTAATCTATATCTGGG TAGCATAGGCTATCCTAATCTATATCTGGGTAGCATATGCTATCC TAATCTATATCTGGGTAGTATATGCTATCCTAATTTATATCTGGG TAGCATAGGCTATCCTAATCTATATCTGGGTAGCATATGCTATCC TAATCTATATCTGGGTAGTATATGCTATCCTAATCTGTATCCGGG TAGCATATGCTATCCTCATGCATATACAGTCAGCATATGATACC CAGTAGTAGAGTGGGAGTGCTATCCTTTGCATATGCCGCCACCT CCCAAGGAGATCTGTCGACATCGATGGGCGCGGGTGTACACTCC GCCCATCCCGCCCCTAACTCCGCCCAGTTCCGCCCATTCTCCGCC TCATGGCTGACTAATTTTTTTTATTTATGCAGAGGCCGAGGCCGC CTCGGCCTCTGAGCTATTCCAGAAGTAGTGAGGAGGCTTTTTTG GAGGCCTAGGCTTTTGCAAAAAGCTAATTCGGCGTAATCTGCTG 2025202995   29 Apr 2025 CTTGCAAACAAAAAAACCACCGCTACCAGCGGTGGTTTGTTTGC CGGATCAAGAGCTACCAACTCTTTTTCCGAAGGTAACTGGCTTC AGCAGAGCGCAGATACCAAATACTGTCCTTCTAGTGTAGCCGTA GTTAGGCCACCACTTCAAGAACTCTGTAGCACCGCCTACATACC TCGCTCTGCTGAAGCCAGTTACCAGTGGCTGCTGCCAGTGGCGA TAAGTCGTGTCTTACCGGGTTGGACTCAAGAGATAGTTACCGGA TAAGGCGCAGCGGTCGGGCTGAACGGGGGGTTCGTGCACACAG CCCAGCTTGGAGCGAACGACCTACACCGAACTGAGATACCTACA GCGTGAGCTATGAGAAAGCGCCACGCTTCCCGAAGGGAGAAAG GCGGACAGGTATCCGGTAAGCGGCAGGGTCGGAACAGGAGAGC GCACGAGGGAGCTTCCAGGGGGAAACGCCTGGTATCTTTATAGT CCTGTCGGGTTTCGCCACCTCTGACTTGAGCGTCGATTTTTGTGA TGCTCGTCAGGGGGGCGGAGCCTATGGAAAAACGCCAGCAACG CAAGCTAGAGTTTAAACTTGACAGATGAGACAATAACCCTGATA AATGCTTCAATAATATTGAAAAAGGAAAAGTATGAGTATTCAAC ATTTCCGTGTCGCCCTTATTCCCTTTTTTGCGGCATTTTGCCTTCC TGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTAAAAGATGCAG AAGATCACTTGGGTGCGCGAGTGGGTTACATCGAACTGGATCTC AACAGCGGTAAGATCCTTGAGAGTTTTCGCCCCGAAGAACGTTT CCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTATT ATCCCGTATTGATGCCGGGCAAGAGCAACTCGGTCGCCGCATAC ACTATTCTCAGAATGACTTGGTTGAATACTCACCAGTCACAGAA AAGCATCTTACGGATGGCATGACAGTAAGAGAATTATGCAGTGC TGCCATAACCATGAGTGATAACACTGCGGCCAACTTACTTCTGA CAACTATCGGAGGACCGAAGGAGCTAACCGCTTTTTTGCACAAC ATGGGGGATCATGTAACTCGCCTTGATCGTTGGGAACCGGAGCT GAATGAAGCCATACCAAACGACGAGCGTGACACCACGATGCCT GTAGCAATGGCAACAACGTTGCGAAAACTATTAACTGGCGAACT ACTTACTCTAGCTTCCCGGCAACAACTAATAGACTGGATGGAGG CGGATAAAGTTGCAGGACCACTTCTGCGCTCGGCACTTCCGGCT GGCTGGTTTATTGCTGATAAATCAGGAGCCGGTGAGCGTGGGTC ACGCGGTATCATTGCAGCACTGGGGCCGGATGGTAAGCCCTCCC GTATCGTAGTTATCTACACTACGGGGAGTCAGGCAACTATGGAT GAACGAAATAGACAGATCGCTGAGATAGGTGCCTCACTGATTAA GCATTGGTAAGGATAAATTTCTGGTAAGGAGGACACGTATGGAA GTGGGCAAGTTGGGGAAGCCGTATCCGTTGCTGAATCTGGCATA TGTGGGAGTATAAGACGCGCAGCGTCGCATCAGGCATTTTTTTC TGCGCCAATGCAAAAAGGCCATCCGTCAGGATGGCCTTTCGGCA TAACTAGTGAGGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACAT CGCCCACAGTCCCCGAGAAGTTGGGGGGAGGGGTCGGCAATTG AACCGGTGCCTAGAGAAGGTGGCGCGGGGTAAACTGGGAAAGT GATGTCGTGTACTGGCTCCGCCTTTTTCCCGAGGGTGGGGGAGA ACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTCTTTTTCGCAA CGGGTTTGCCGCCAGAACACAGGTAAGTGCCGTGTGTGGTTCCC GCGGGCCTGGCCTCTTTACGGGTTATGGCCCTTGCGTGCCTTGAA TTACTTCCACCTGGCTGCAGTACGTGATTCTTGATCCCGAGCTTC GGGTTGGAAGTGGGTGGGAGAGTTCGAGGCCTTGCGCTTAAGGA GCCCCTTCGCCTCGTGCTTGAGTTGAGGCCTGGCCTGGGCGCTG GGGCCGCCGCGTGCGAATCTGGTGGCACCTTCGCGCCTGTCTCG CTGCTTTCGATAAGTCTCTAGCCATTTAAAATTTTTGATGACCTG CTGCGACGCTTTTTTTCTGGCAAGATAGTCTTGTAAATGCGGGCC 2025202995   29 Apr 2025 AAGACGATCTGCACACTGGTATTTCGGTTTTTGGGGCCGCGGGC GGCGACGGGGCCCGTGCGTCCCAGCGCACATGTTCGGCGAGGC GGGGCCTGCGAGCGCGGCCACCGAGAATCGGACGGGGGTAGTC TCAAGCTGGCCGGCCTGCTCTGGTGCCTGGCCTCGCGCCGCCGT GTATCGCCCCGCCCTGGGCGGCAAGGCTGGCCCGGTCGGCACCA GTTGCGTGAGCGGAAAGATGGCCGCTTCCCGGCCCTGCTGCAGG GAGCTCAAAATGGAGGACGCGGCGCTCGGGAGAGCGGGCGGGT GAGTCACCCACACAAAGGAAAAGGGCCTTTCCGTCCTCAGCCGT CGCTTCATGTGACTCCACGGAGTACCGGGCGCCGTCCAGGCACC TCGATTAGTTCTCGAGCTTTTGGAGTACGTCGTCTTTAGGTTGGG GGGAGGGGTTTTATGCGATGGAGTTTCCCCACACTGAGTGGGTG GAGACTGAAGTTAGGCCAGCTTGGCACTTGATGTAATTCTCCTT GGAATTTGCCCTTTTTGAGTTTGGATCTTGGTTCATTCTCAAGCC TCAGACAGTGGTTCAAAGTTTTTTTCTTCCATTTCAGGTGTCGTG AAA 12 P-NR-027 plasmid AGCTAGCTTTAATACGACTCACTATAAGGAAATAAGAGAGAAA AGAAGAGTAAGAAGAAATATAAGAGCCACCATGAAATCCTTGA GAGTTTTACTAGTGATCCTGTGGCTTCAGTTGAGCTGGGTTTGGA GCCAACAGAAGGAGGTGGAGCAGAATTCTGGACCCCTCAGTGTT CCAGAGGGAGCCATTGCCTCTCTCAACTGCACTTACAGTGACCG AGGTTCCCAGTCCTTCTTCTGGTACAGACAATATTCTGGGAAAA GCCCTGAGTTGATAATGTCCATATACTCCAATGGTGACAAAGAA GATGGAAGGTTTACAGCACAGCTCAATAAAGCCAGCCAGTATGT TTCTCTGCTCATCAGAGACTCCCAGCCCAGTGATTCAGCCACCTA CCTCTGTGCCGTGAACGTCCCCTTGAGTTACCAACTCACTTTCGG GAAGGGGACCAAACTCTCGGTCATACCAAATGCCGGATCTAGTA CAGGTAGCTCCACTGGGCCGGGTAGCACATCAGTTGATGAGTTG CAGGCCGAGGTGGACCAGCTTCAAGATGAGAACTACGCTCTGA AAACGAAAGTAGCACAGTTGCGAAAAAAGGTAGAGAAGCTCGC GTCTGGTGGATGTGGTGGAGAGTTTGATGCTCCAAGCCCTCTCC CAGAGACTACAGAGAACGTGGTGTGTGCCCTGGGCCTGACTGTG GGTCTGGTGGGCATCATTATTGGGACCATCTTCATCATCAGGAG TAAGAGGAGCAGGCTCCTGCACAGTGACTACATGAACATGACTC CCCGCCGCCCCGGGCCCACCCGCAAGCATTACCAGCCCTATGCC CCACCACGCGACTTCGCAGCCTATCGCTCCAGAGTGAAGTTCAG CAGGAGCGCAGACGCCCCCGCGTACCAGCAGGGCCAGAACCAG CTCTATAACGAGCTCAATCTAGGACGAAGAGAGGAGTACGATGT TTTGGACAAGAGACGTGGCCGGGACCCTGAGATGGGGGGAAAG CCGCAGAGAAGGAAGAACCCTCAGGAAGGCCTGTACAATGAAC TGCAGAAAGATAAGATGGCGGAGGCCTACAGTGAGATTGGGAT GAAAGGCGAGCGCCGGAGGGGCAAGGGGCACGATGGCCTTTAC CAGGGTCTCAGTACAGCCACCAAGGACACCTACGACGCCCTTCA CATGCAGGCCCTGCCCCCTCGCTGATTAATTAAGCTGCCTTCTGC GGGGCTTGCCTTCTGGCCATGCCCTTCTTCTCTCCCTTGCACCTG TACCTCTTGGTCTTTGAATAAAGCCTGAGTAGGAAGAAAAAAAA AAAAAAAAAAAAAAAGCAGGTGGCGGCCGCAGGTAAGCCAGCC CAGGCCTCGCCCTCCAGCTCAAGGCGGGACAGGTGCCCTAGAGT AGCCTGCATCCAGGGACAGGCCCCAGCCGGGTGCTGACACGTCC ACCTCCATCTCTTCCTCAGGTCTGCCCGGGTGGCATCCCTGTGAC CCCTCCCCAGTGCCTCTCCTGGTCGTGGAAGGTGCTACTCCAGTG CCCACCAGCCTTGTCCTAATAAAATTAAGTTGCATCATTTTGTTT 2025202995   29 Apr 2025 GACTAGGTGTCCTTGTATAATATTATGGGGTGGAGGCGGGTGGT ATGGAGCAAGGGGCCCAAGTTAACTTGTTTATTGCAGCTTATAA TGGTTACAAATAAAGCAATAGCATCACAAATTTCACAAATAAAG CATTTTTTTCACTGCATTCTAGTTGTGGTTTGTCCAAACTCATCA ATGTATCTTATCATGTCTGGATCCGCTTCAGGCACCGGGCTTGCG GGTCATGCACCAGGTGCGCGGTCCTTCGGGCACCTCGACGTCGG CGGTGACGGTGAAGCCGAGCCGCTCGTAGAAGGGGAGGTTGCG GGGCGCGGAGGTCTCCAGGAAGGCGGGCACCCCGGCGCGCTCG GCCGCCTCCACTCCGGGGAGCACGACGGCGCTGCCCAGACCCTT GCCCTGGTGGTCGGGCGAGACGCCGACGGTGGCCAGGAACCAC GCGGGCTCCTTGGGCCGGTGCGGCGCCAGGAGGCCTTCCATCTG TTGCTGCGCGGCCAGCCTGGAACCGCTCAACTCGGCCATGCGCG GGCCGATCTCGGCGAACACCGCCCCCGCTTCGACGCTCTCCGGC GTGGTCCAGACCGCCACCGCGGCGCCGTCGTCCGCGACCCACAC CTTGCCGATGTCGAGCCCGACGCGCGTGAGGAAGAGTTCTTGCA GCTCGGTGACCCGCTCGATGTGGCGGTCCGGGTCGACGGTGTGG CGCGTGGCGGGGTAGTCGGCGAACGCGGCGGCGAGGGTGCGTA CGGCCCGGGGGACGTCGTCGCGGGTGGCGAGGCGCACCGTGGG CTTGTACTCGGTCATGGTGGCCTGCAGAGTCGCTCTGTGTTCGAG GCCACACGCGTCACCTTAATATGCGAAGTGGACCTGGGACCGCG CCGCCCCGACTGCATCTGCGTGTTTTCGCCAATGACAAGACGCT GGGCGGGGTTTGTGTCATCATAGAACTAAAGACATGCAAATATA TTTCTTCCGGGGACACCGCCAGCAAACGCGAGCAACGGGCCACG GGGATGAAGCAGCTGCGCCACTCCCTGAAGATCCATCGTCTCCT AACAAGTTACATCACTCCTGCCCTTCCTCACCCTCATCTCCATCA CCTCCTTCATCTCCGTCATCTCCGTCATCACCCTCCGCGGCAGCC CCTTCCACCATAGGTGGAAACCAGGGAGGCAAATCTACTCCATC GTCAAAGCTGCACACAGTCACCCTGATATTGCAGGTAGGAGCGG GCTTTGTCATAACAAGGTCCTTAATCGCATCCTTCAAAACCTCAG CAAATATATGAGTTTGTAAAAAGACCATGAAATAACAGACAATG GACTCCCTTAGCGGGCCAGGTTGTGGGCCGGGTCCAGGGGCCAT TCCAAAGGGGAGACGACTCAATGGTGTAAGACGACATTGTGGA ATAGCAAGGGCAGTTCCTCGCCTTAGGTTGTAAAGGGAGGTCTT ACTACCTCCATATACGAACACACCGGCGACCCAAGTTCCTTCGT CGGTAGTCCTTTCTACGTGACTCCTAGCCAGGAGAGCTCTTAAA CCTTCTGCAATGTTCTCAAATTTCGGGTTGGAACCTCCTTGACCA CGATGCTTTCCAAACCACCCTCCTTTTTTGCGCCTGCCTCCATCA CCCTGACCCCCGCTGCGCGGGGGCACGTCAGGCTCACCATCTGG GCCGCCTTCTTGGTGGTATTCAAAATAATCGGCTTCCCCTACAGG GTGGAAAAATGGCCTTCTACCTGGAGGGGGCCTGCGCGGTGGA GACCCGGATGATGATGACTGACTACTGGGACTCCTGGGCCTCTT TTCTCCACGTCCACGACCTCTCCCCCTGGCTCTTTCACGACTTCC CCCCCTGGCTCTTTCACGTCCTCTACCCCGGCGGCCTCCACTACC TCCTCGACCCCGGCCTCCACTACCTCCTCGACCCCGGCCTCCACT GCCTCCTCGACCCCGGCCTCCACCTCCTGCTCCTGCCCCTCCCGC TCCTGCTCCTGCTCCTGTTCCACCGTGGGTCCCTTTGCAGCCAAT GCAACTTGGACGTTTTTGGGGTCTCCGGACACCATCTCTATGTCT TGGCCCTGATCCTGAGCCGCCCGGGGCTCCTGGTCTTCCGCCTCC TCGTCCTCGTCCTCTTCCCCGTCCTCGTCCATGTGCCATGATGGC GGCCTGCAGCTGTGTTCGAGGCCGCGCGTGTCACCTTAATATGC GAAGTGGACCTGGGACCGCGCCGCCCCGACTGCATCTGCGTGTT 2025202995   29 Apr 2025 CGAGTTCGCCAATGACAAGACGCTGGGCGGGGAGATCCCCCTTA TTAACCCTAAACGGGTAGCATATGCTTCCCGGGTAGTAGTATAT ACTATCCAGACTAACCCTAATTCAATAGCATATGTTACCCAACG GGAAGCATATGCTATCGAATTAGGGTTAGTAAAAGGGTCCTAAG GAACAGCGATCTGGATAGCATATGCTATCCTAATCTATATCTGG GTAGCATATGCTATCCTAATCTATATCTGGGTAGCATAGGCTATC CTAATCTATATCTGGGTAGCATATGCTATCCTAATCTATATCTGG GTAGTATATGCTATCCTAATTTATATCTGGGTAGCATAGGCTATC CTAATCTATATCTGGGTAGCATATGCTATCCTAATCTATATCTGG GTAGTATATGCTATCCTAATCTGTATCCGGGTAGCATATGCTATC CTCATGCATATACAGTCAGCATATGATACCCAGTAGTAGAGTGG GAGTGCTATCCTTTGCATATGCCGCCACCTCCCAAGGAGATCTG TCGACATCGATGGGCGCGGGTGTACACTCCGCCCATCCCGCCCC TAACTCCGCCCAGTTCCGCCCATTCTCCGCCTCATGGCTGACTAA TTTTTTTTATTTATGCAGAGGCCGAGGCCGCCTCGGCCTCTGAGC TATTCCAGAAGTAGTGAGGAGGCTTTTTTGGAGGCCTAGGCTTTT GCAAAAAGCTAATTCGGCGTAATCTGCTGCTTGCAAACAAAAAA ACCACCGCTACCAGCGGTGGTTTGTTTGCCGGATCAAGAGCTAC CAACTCTTTTTCCGAAGGTAACTGGCTTCAGCAGAGCGCAGATA CCAAATACTGTCCTTCTAGTGTAGCCGTAGTTAGGCCACCACTTC AAGAACTCTGTAGCACCGCCTACATACCTCGCTCTGCTGAAGCC AGTTACCAGTGGCTGCTGCCAGTGGCGATAAGTCGTGTCTTACC GGGTTGGACTCAAGAGATAGTTACCGGATAAGGCGCAGCGGTC GGGCTGAACGGGGGGTTCGTGCACACAGCCCAGCTTGGAGCGA ACGACCTACACCGAACTGAGATACCTACAGCGTGAGCTATGAGA AAGCGCCACGCTTCCCGAAGGGAGAAAGGCGGACAGGTATCCG GTAAGCGGCAGGGTCGGAACAGGAGAGCGCACGAGGGAGCTTC CAGGGGGAAACGCCTGGTATCTTTATAGTCCTGTCGGGTTTCGC CACCTCTGACTTGAGCGTCGATTTTTGTGATGCTCGTCAGGGGGG CGGAGCCTATGGAAAAACGCCAGCAACGCAAGCTAGAGTTTAA ACTTGACAGATGAGACAATAACCCTGATAAATGCTTCAATAATA TTGAAAAAGGAAAAGTATGAGTATTCAACATTTCCGTGTCGCCC TTATTCCCTTTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCACCC AGAAACGCTGGTGAAAGTAAAAGATGCAGAAGATCACTTGGGT GCGCGAGTGGGTTACATCGAACTGGATCTCAACAGCGGTAAGAT CCTTGAGAGTTTTCGCCCCGAAGAACGTTTCCCAATGATGAGCA CTTTTAAAGTTCTGCTATGTGGCGCGGTATTATCCCGTATTGATG CCGGGCAAGAGCAACTCGGTCGCCGCATACACTATTCTCAGAAT GACTTGGTTGAATACTCACCAGTCACAGAAAAGCATCTTACGGA TGGCATGACAGTAAGAGAATTATGCAGTGCTGCCATAACCATGA GTGATAACACTGCGGCCAACTTACTTCTGACAACTATCGGAGGA CCGAAGGAGCTAACCGCTTTTTTGCACAACATGGGGGATCATGT AACTCGCCTTGATCGTTGGGAACCGGAGCTGAATGAAGCCATAC CAAACGACGAGCGTGACACCACGATGCCTGTAGCAATGGCAAC AACGTTGCGAAAACTATTAACTGGCGAACTACTTACTCTAGCTT CCCGGCAACAACTAATAGACTGGATGGAGGCGGATAAAGTTGC AGGACCACTTCTGCGCTCGGCACTTCCGGCTGGCTGGTTTATTGC TGATAAATCAGGAGCCGGTGAGCGTGGGTCACGCGGTATCATTG CAGCACTGGGGCCGGATGGTAAGCCCTCCCGTATCGTAGTTATC TACACTACGGGGAGTCAGGCAACTATGGATGAACGAAATAGAC AGATCGCTGAGATAGGTGCCTCACTGATTAAGCATTGGTAAGGA 2025202995   29 Apr 2025 TAAATTTCTGGTAAGGAGGACACGTATGGAAGTGGGCAAGTTGG GGAAGCCGTATCCGTTGCTGAATCTGGCATATGTGGGAGTATAA GACGCGCAGCGTCGCATCAGGCATTTTTTTCTGCGCCAATGCAA AAAGGCCATCCGTCAGGATGGCCTTTCGGCATAACTAGTGAGGC TCCGGTGCCCGTCAGTGGGCAGAGCGCACATCGCCCACAGTCCC CGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACCGGTGCCTAG AGAAGGTGGCGCGGGGTAAACTGGGAAAGTGATGTCGTGTACT GGCTCCGCCTTTTTCCCGAGGGTGGGGGAGAACCGTATATAAGT GCAGTAGTCGCCGTGAACGTTCTTTTTCGCAACGGGTTTGCCGCC AGAACACAGGTAAGTGCCGTGTGTGGTTCCCGCGGGCCTGGCCT CTTTACGGGTTATGGCCCTTGCGTGCCTTGAATTACTTCCACCTG GCTGCAGTACGTGATTCTTGATCCCGAGCTTCGGGTTGGAAGTG GGTGGGAGAGTTCGAGGCCTTGCGCTTAAGGAGCCCCTTCGCCT CGTGCTTGAGTTGAGGCCTGGCCTGGGCGCTGGGGCCGCCGCGT GCGAATCTGGTGGCACCTTCGCGCCTGTCTCGCTGCTTTCGATAA GTCTCTAGCCATTTAAAATTTTTGATGACCTGCTGCGACGCTTTT TTTCTGGCAAGATAGTCTTGTAAATGCGGGCCAAGACGATCTGC ACACTGGTATTTCGGTTTTTGGGGCCGCGGGCGGCGACGGGGCC CGTGCGTCCCAGCGCACATGTTCGGCGAGGCGGGGCCTGCGAGC GCGGCCACCGAGAATCGGACGGGGGTAGTCTCAAGCTGGCCGG CCTGCTCTGGTGCCTGGCCTCGCGCCGCCGTGTATCGCCCCGCCC TGGGCGGCAAGGCTGGCCCGGTCGGCACCAGTTGCGTGAGCGG AAAGATGGCCGCTTCCCGGCCCTGCTGCAGGGAGCTCAAAATGG AGGACGCGGCGCTCGGGAGAGCGGGCGGGTGAGTCACCCACAC AAAGGAAAAGGGCCTTTCCGTCCTCAGCCGTCGCTTCATGTGAC TCCACGGAGTACCGGGCGCCGTCCAGGCACCTCGATTAGTTCTC GAGCTTTTGGAGTACGTCGTCTTTAGGTTGGGGGGAGGGGTTTT ATGCGATGGAGTTTCCCCACACTGAGTGGGTGGAGACTGAAGTT AGGCCAGCTTGGCACTTGATGTAATTCTCCTTGGAATTTGCCCTT TTTGAGTTTGGATCTTGGTTCATTCTCAAGCCTCAGACAGTGGTT CAAAGTTTTTTTCTTCCATTTCAGGTGTCGTGAAA 13 P-NR-024 plasmid AGCTAGCTTTAATACGACTCACTATAAGGAAATAAGAGAGAAA AGAAGAGTAAGAAGAAATATAAGAGCCACCATGGGCTAGTACA GATATCAGGATCTACCAGCGGCACGGGCTCTACTACGGTGGCCC AACTCAGGGAACGGGTCAAGACACTGAGAGCCCAAAATTACGA ATTGGAGTCTGAGGTTCAACGCCTTCGAGAGCAAGTTGCGCAGC TTGCAAGTGGTGGATGTGGTGGAAGAGCACGGTCTGAATCTGCA CAGAGCAAGATGCTGAGTGGAGTCGGGGGCTTTGTGCTGGGCCT GCTCTTCCTTGGGGCCGGGCTGTTCATCAGGAGTAAGAGGAGCA GGCTCCTGCACAGTGACTACATGAACATGACTCCCCGCCGCCCC GGGCCCACCCGCAAGCATTACCAGCCCTATGCCCCACCACGCGA CTTCGCAGCCTATCGCTCCAGAGTGAAGTTCAGCAGGAGCGCAG ACGCCCCCGCGTACCAGCAGGGCCAGAACCAGCTCTATAACGA GCTCAATCTAGGACGAAGAGAGGAGTACGATGTTTTGGACAAG AGACGTGGCCGGGACCCTGAGATGGGGGGAAAGCCGCAGAGAA GGAAGAACCCTCAGGAAGGCCTGTACAATGAACTGCAGAAAGA TAAGATGGCGGAGGCCTACAGTGAGATTGGGATGAAAGGCGAG CGCCGGAGGGGCAAGGGGCACGATGGCCTTTACCAGGGTCTCA GTACAGCCACCAAGGACACCTACGACGCCCTTCACATGCAGGCC CTGCCCCCTCGCTGATTAATTAAGCTGCCTTCTGCGGGGCTTGCC TTCTGGCCATGCCCTTCTTCTCTCCCTTGCACCTGTACCTCTTGGT 2025202995   29 Apr 2025 CTTTGAATAAAGCCTGAGTAGGAAGAAAAAAAAAAAAAAAAAA AAAAAGCAGGTGGCGGCCGCAGGTAAGCCAGCCCAGGCCTCGC CCTCCAGCTCAAGGCGGGACAGGTGCCCTAGAGTAGCCTGCATC CAGGGACAGGCCCCAGCCGGGTGCTGACACGTCCACCTCCATCT CTTCCTCAGGTCTGCCCGGGTGGCATCCCTGTGACCCCTCCCCAG TGCCTCTCCTGGTCGTGGAAGGTGCTACTCCAGTGCCCACCAGC CTTGTCCTAATAAAATTAAGTTGCATCATTTTGTTTGACTAGGTG TCCTTGTATAATATTATGGGGTGGAGGCGGGTGGTATGGAGCAA GGGGCCCAAGTTAACTTGTTTATTGCAGCTTATAATGGTTACAA ATAAAGCAATAGCATCACAAATTTCACAAATAAAGCATTTTTTT CACTGCATTCTAGTTGTGGTTTGTCCAAACTCATCAATGTATCTT ATCATGTCTGGATCCGCTTCAGGCACCGGGCTTGCGGGTCATGC ACCAGGTGCGCGGTCCTTCGGGCACCTCGACGTCGGCGGTGACG GTGAAGCCGAGCCGCTCGTAGAAGGGGAGGTTGCGGGGCGCGG AGGTCTCCAGGAAGGCGGGCACCCCGGCGCGCTCGGCCGCCTCC ACTCCGGGGAGCACGACGGCGCTGCCCAGACCCTTGCCCTGGTG GTCGGGCGAGACGCCGACGGTGGCCAGGAACCACGCGGGCTCC TTGGGCCGGTGCGGCGCCAGGAGGCCTTCCATCTGTTGCTGCGC GGCCAGCCTGGAACCGCTCAACTCGGCCATGCGCGGGCCGATCT CGGCGAACACCGCCCCCGCTTCGACGCTCTCCGGCGTGGTCCAG ACCGCCACCGCGGCGCCGTCGTCCGCGACCCACACCTTGCCGAT GTCGAGCCCGACGCGCGTGAGGAAGAGTTCTTGCAGCTCGGTGA CCCGCTCGATGTGGCGGTCCGGGTCGACGGTGTGGCGCGTGGCG GGGTAGTCGGCGAACGCGGCGGCGAGGGTGCGTACGGCCCGGG GGACGTCGTCGCGGGTGGCGAGGCGCACCGTGGGCTTGTACTCG GTCATGGTGGCCTGCAGAGTCGCTCTGTGTTCGAGGCCACACGC GTCACCTTAATATGCGAAGTGGACCTGGGACCGCGCCGCCCCGA CTGCATCTGCGTGTTTTCGCCAATGACAAGACGCTGGGCGGGGT TTGTGTCATCATAGAACTAAAGACATGCAAATATATTTCTTCCGG GGACACCGCCAGCAAACGCGAGCAACGGGCCACGGGGATGAAG CAGCTGCGCCACTCCCTGAAGATCCATCGTCTCCTAACAAGTTA CATCACTCCTGCCCTTCCTCACCCTCATCTCCATCACCTCCTTCAT CTCCGTCATCTCCGTCATCACCCTCCGCGGCAGCCCCTTCCACCA TAGGTGGAAACCAGGGAGGCAAATCTACTCCATCGTCAAAGCTG CACACAGTCACCCTGATATTGCAGGTAGGAGCGGGCTTTGTCAT AACAAGGTCCTTAATCGCATCCTTCAAAACCTCAGCAAATATAT GAGTTTGTAAAAAGACCATGAAATAACAGACAATGGACTCCCTT AGCGGGCCAGGTTGTGGGCCGGGTCCAGGGGCCATTCCAAAGG GGAGACGACTCAATGGTGTAAGACGACATTGTGGAATAGCAAG GGCAGTTCCTCGCCTTAGGTTGTAAAGGGAGGTCTTACTACCTC CATATACGAACACACCGGCGACCCAAGTTCCTTCGTCGGTAGTC CTTTCTACGTGACTCCTAGCCAGGAGAGCTCTTAAACCTTCTGCA ATGTTCTCAAATTTCGGGTTGGAACCTCCTTGACCACGATGCTTT CCAAACCACCCTCCTTTTTTGCGCCTGCCTCCATCACCCTGACCC CCGCTGCGCGGGGGCACGTCAGGCTCACCATCTGGGCCGCCTTC TTGGTGGTATTCAAAATAATCGGCTTCCCCTACAGGGTGGAAAA ATGGCCTTCTACCTGGAGGGGGCCTGCGCGGTGGAGACCCGGAT GATGATGACTGACTACTGGGACTCCTGGGCCTCTTTTCTCCACGT CCACGACCTCTCCCCCTGGCTCTTTCACGACTTCCCCCCCTGGCT CTTTCACGTCCTCTACCCCGGCGGCCTCCACTACCTCCTCGACCC CGGCCTCCACTACCTCCTCGACCCCGGCCTCCACTGCCTCCTCGA 2025202995   29 Apr 2025 CCCCGGCCTCCACCTCCTGCTCCTGCCCCTCCCGCTCCTGCTCCT GCTCCTGTTCCACCGTGGGTCCCTTTGCAGCCAATGCAACTTGGA CGTTTTTGGGGTCTCCGGACACCATCTCTATGTCTTGGCCCTGAT CCTGAGCCGCCCGGGGCTCCTGGTCTTCCGCCTCCTCGTCCTCGT CCTCTTCCCCGTCCTCGTCCATGTGCCATGATGGCGGCCTGCAGC TGTGTTCGAGGCCGCGCGTGTCACCTTAATATGCGAAGTGGACC TGGGACCGCGCCGCCCCGACTGCATCTGCGTGTTCGAGTTCGCC AATGACAAGACGCTGGGCGGGGAGATCCCCCTTATTAACCCTAA ACGGGTAGCATATGCTTCCCGGGTAGTAGTATATACTATCCAGA CTAACCCTAATTCAATAGCATATGTTACCCAACGGGAAGCATAT GCTATCGAATTAGGGTTAGTAAAAGGGTCCTAAGGAACAGCGAT CTGGATAGCATATGCTATCCTAATCTATATCTGGGTAGCATATGC TATCCTAATCTATATCTGGGTAGCATAGGCTATCCTAATCTATAT CTGGGTAGCATATGCTATCCTAATCTATATCTGGGTAGTATATGC TATCCTAATTTATATCTGGGTAGCATAGGCTATCCTAATCTATAT CTGGGTAGCATATGCTATCCTAATCTATATCTGGGTAGTATATGC TATCCTAATCTGTATCCGGGTAGCATATGCTATCCTCATGCATAT ACAGTCAGCATATGATACCCAGTAGTAGAGTGGGAGTGCTATCC TTTGCATATGCCGCCACCTCCCAAGGAGATCTGTCGACATCGAT GGGCGCGGGTGTACACTCCGCCCATCCCGCCCCTAACTCCGCCC AGTTCCGCCCATTCTCCGCCTCATGGCTGACTAATTTTTTTTATTT ATGCAGAGGCCGAGGCCGCCTCGGCCTCTGAGCTATTCCAGAAG TAGTGAGGAGGCTTTTTTGGAGGCCTAGGCTTTTGCAAAAAGCT AATTCGGCGTAATCTGCTGCTTGCAAACAAAAAAACCACCGCTA CCAGCGGTGGTTTGTTTGCCGGATCAAGAGCTACCAACTCTTTTT CCGAAGGTAACTGGCTTCAGCAGAGCGCAGATACCAAATACTGT CCTTCTAGTGTAGCCGTAGTTAGGCCACCACTTCAAGAACTCTGT AGCACCGCCTACATACCTCGCTCTGCTGAAGCCAGTTACCAGTG GCTGCTGCCAGTGGCGATAAGTCGTGTCTTACCGGGTTGGACTC AAGAGATAGTTACCGGATAAGGCGCAGCGGTCGGGCTGAACGG GGGGTTCGTGCACACAGCCCAGCTTGGAGCGAACGACCTACACC GAACTGAGATACCTACAGCGTGAGCTATGAGAAAGCGCCACGC TTCCCGAAGGGAGAAAGGCGGACAGGTATCCGGTAAGCGGCAG GGTCGGAACAGGAGAGCGCACGAGGGAGCTTCCAGGGGGAAAC GCCTGGTATCTTTATAGTCCTGTCGGGTTTCGCCACCTCTGACTT GAGCGTCGATTTTTGTGATGCTCGTCAGGGGGGCGGAGCCTATG GAAAAACGCCAGCAACGCAAGCTAGAGTTTAAACTTGACAGAT GAGACAATAACCCTGATAAATGCTTCAATAATATTGAAAAAGGA AAAGTATGAGTATTCAACATTTCCGTGTCGCCCTTATTCCCTTTT TTGCGGCATTTTGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGG TGAAAGTAAAAGATGCAGAAGATCACTTGGGTGCGCGAGTGGG TTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTGAGAGTT TTCGCCCCGAAGAACGTTTCCCAATGATGAGCACTTTTAAAGTT CTGCTATGTGGCGCGGTATTATCCCGTATTGATGCCGGGCAAGA GCAACTCGGTCGCCGCATACACTATTCTCAGAATGACTTGGTTG AATACTCACCAGTCACAGAAAAGCATCTTACGGATGGCATGACA GTAAGAGAATTATGCAGTGCTGCCATAACCATGAGTGATAACAC TGCGGCCAACTTACTTCTGACAACTATCGGAGGACCGAAGGAGC TAACCGCTTTTTTGCACAACATGGGGGATCATGTAACTCGCCTTG ATCGTTGGGAACCGGAGCTGAATGAAGCCATACCAAACGACGA GCGTGACACCACGATGCCTGTAGCAATGGCAACAACGTTGCGAA 2025202995   29 Apr 2025 AACTATTAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAA CTAATAGACTGGATGGAGGCGGATAAAGTTGCAGGACCACTTCT GCGCTCGGCACTTCCGGCTGGCTGGTTTATTGCTGATAAATCAG GAGCCGGTGAGCGTGGGTCACGCGGTATCATTGCAGCACTGGGG CCGGATGGTAAGCCCTCCCGTATCGTAGTTATCTACACTACGGG GAGTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGAG ATAGGTGCCTCACTGATTAAGCATTGGTAAGGATAAATTTCTGG TAAGGAGGACACGTATGGAAGTGGGCAAGTTGGGGAAGCCGTA TCCGTTGCTGAATCTGGCATATGTGGGAGTATAAGACGCGCAGC GTCGCATCAGGCATTTTTTTCTGCGCCAATGCAAAAAGGCCATC CGTCAGGATGGCCTTTCGGCATAACTAGTGAGGCTCCGGTGCCC GTCAGTGGGCAGAGCGCACATCGCCCACAGTCCCCGAGAAGTTG GGGGGAGGGGTCGGCAATTGAACCGGTGCCTAGAGAAGGTGGC GCGGGGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCTT TTTCCCGAGGGTGGGGGAGAACCGTATATAAGTGCAGTAGTCGC CGTGAACGTTCTTTTTCGCAACGGGTTTGCCGCCAGAACACAGG TAAGTGCCGTGTGTGGTTCCCGCGGGCCTGGCCTCTTTACGGGTT ATGGCCCTTGCGTGCCTTGAATTACTTCCACCTGGCTGCAGTACG TGATTCTTGATCCCGAGCTTCGGGTTGGAAGTGGGTGGGAGAGT TCGAGGCCTTGCGCTTAAGGAGCCCCTTCGCCTCGTGCTTGAGTT GAGGCCTGGCCTGGGCGCTGGGGCCGCCGCGTGCGAATCTGGTG GCACCTTCGCGCCTGTCTCGCTGCTTTCGATAAGTCTCTAGCCAT TTAAAATTTTTGATGACCTGCTGCGACGCTTTTTTTCTGGCAAGA TAGTCTTGTAAATGCGGGCCAAGACGATCTGCACACTGGTATTT CGGTTTTTGGGGCCGCGGGCGGCGACGGGGCCCGTGCGTCCCAG CGCACATGTTCGGCGAGGCGGGGCCTGCGAGCGCGGCCACCGA GAATCGGACGGGGGTAGTCTCAAGCTGGCCGGCCTGCTCTGGTG CCTGGCCTCGCGCCGCCGTGTATCGCCCCGCCCTGGGCGGCAAG GCTGGCCCGGTCGGCACCAGTTGCGTGAGCGGAAAGATGGCCG CTTCCCGGCCCTGCTGCAGGGAGCTCAAAATGGAGGACGCGGCG CTCGGGAGAGCGGGCGGGTGAGTCACCCACACAAAGGAAAAGG GCCTTTCCGTCCTCAGCCGTCGCTTCATGTGACTCCACGGAGTAC CGGGCGCCGTCCAGGCACCTCGATTAGTTCTCGAGCTTTTGGAG TACGTCGTCTTTAGGTTGGGGGGAGGGGTTTTATGCGATGGAGT TTCCCCACACTGAGTGGGTGGAGACTGAAGTTAGGCCAGCTTGG CACTTGATGTAATTCTCCTTGGAATTTGCCCTTTTTGAGTTTGGA TCTTGGTTCATTCTCAAGCCTCAGACAGTGGTTCAAAGTTTTTTT CTTCCATTTCAGGTGTCGTGAAA 14 P-NR-028 plasmid AGCTAGCTTTAATACGACTCACTATAAGGAAATAAGAGAGAAA AGAAGAGTAAGAAGAAATATAAGAGCCACCATGCTGAGTCTTCT GCTCCTTCTCCTGGGACTAGGCTCTGTGTTCAGTGCTGTCATCTC TCAAAAGCCAAGCAGGGATATCTGTCAACGTGGAACCTCCCTGA CGATCCAGTGTCAAGTCGATAGCCAAGTCACCATGATGTTCTGG TACCGTCAGCAACCTGGACAGAGCCTGACACTGATCGCAACTGC AAATCAGGGCTCTGAGGCCACATATGAGAGTGGATTTGTCATTG ACAAGTTTCCCATCAGCCGCCCAAACCTAACATTCTCAACTCTG ACTGTGAGCAACATGAGCCCTGAAGACAGCAGCATATATCTCTG CAGCGTTGCCGGGACTATCGACGAGCAGTACTTCGGGCCGGGCA CCAGGCTCACGGTCACAGAGAGTGGGGGCACATCAGGATCTAC CAGCGGCACGGGCTCTACTACGGTGGCCCAACTCAGGGAACGG GTCAAGACACTGAGAGCCCAAAATTACGAATTGGAGTCTGAGGT 2025202995   29 Apr 2025 TCAACGCCTTCGAGAGCAAGTTGCGCAGCTTGCAAGTGGTGGAT GTGGTGGAAGAGCACGGTCTGAATCTGCACAGAGCAAGATGCT GAGTGGAGTCGGGGGCTTTGTGCTGGGCCTGCTCTTCCTTGGGG CCGGGCTGTTCATCAGGAGTAAGAGGAGCAGGCTCCTGCACAGT GACTACATGAACATGACTCCCCGCCGCCCCGGGCCCACCCGCAA GCATTACCAGCCCTATGCCCCACCACGCGACTTCGCAGCCTATC GCTCCAGAGTGAAGTTCAGCAGGAGCGCAGACGCCCCCGCGTA CCAGCAGGGCCAGAACCAGCTCTATAACGAGCTCAATCTAGGAC GAAGAGAGGAGTACGATGTTTTGGACAAGAGACGTGGCCGGGA CCCTGAGATGGGGGGAAAGCCGCAGAGAAGGAAGAACCCTCAG GAAGGCCTGTACAATGAACTGCAGAAAGATAAGATGGCGGAGG CCTACAGTGAGATTGGGATGAAAGGCGAGCGCCGGAGGGGCAA GGGGCACGATGGCCTTTACCAGGGTCTCAGTACAGCCACCAAGG ACACCTACGACGCCCTTCACATGCAGGCCCTGCCCCCTCGCTGA TTAATTAAGCTGCCTTCTGCGGGGCTTGCCTTCTGGCCATGCCCT TCTTCTCTCCCTTGCACCTGTACCTCTTGGTCTTTGAATAAAGCC TGAGTAGGAAGAAAAAAAAAAAAAAAAAAAAAAAGCAGGTGG CGGCCGCAGGTAAGCCAGCCCAGGCCTCGCCCTCCAGCTCAAGG CGGGACAGGTGCCCTAGAGTAGCCTGCATCCAGGGACAGGCCC CAGCCGGGTGCTGACACGTCCACCTCCATCTCTTCCTCAGGTCTG CCCGGGTGGCATCCCTGTGACCCCTCCCCAGTGCCTCTCCTGGTC GTGGAAGGTGCTACTCCAGTGCCCACCAGCCTTGTCCTAATAAA ATTAAGTTGCATCATTTTGTTTGACTAGGTGTCCTTGTATAATAT TATGGGGTGGAGGCGGGTGGTATGGAGCAAGGGGCCCAAGTTA ACTTGTTTATTGCAGCTTATAATGGTTACAAATAAAGCAATAGC ATCACAAATTTCACAAATAAAGCATTTTTTTCACTGCATTCTAGT TGTGGTTTGTCCAAACTCATCAATGTATCTTATCATGTCTGGATC CGCTTCAGGCACCGGGCTTGCGGGTCATGCACCAGGTGCGCGGT CCTTCGGGCACCTCGACGTCGGCGGTGACGGTGAAGCCGAGCCG CTCGTAGAAGGGGAGGTTGCGGGGCGCGGAGGTCTCCAGGAAG GCGGGCACCCCGGCGCGCTCGGCCGCCTCCACTCCGGGGAGCAC GACGGCGCTGCCCAGACCCTTGCCCTGGTGGTCGGGCGAGACGC CGACGGTGGCCAGGAACCACGCGGGCTCCTTGGGCCGGTGCGG CGCCAGGAGGCCTTCCATCTGTTGCTGCGCGGCCAGCCTGGAAC CGCTCAACTCGGCCATGCGCGGGCCGATCTCGGCGAACACCGCC CCCGCTTCGACGCTCTCCGGCGTGGTCCAGACCGCCACCGCGGC GCCGTCGTCCGCGACCCACACCTTGCCGATGTCGAGCCCGACGC GCGTGAGGAAGAGTTCTTGCAGCTCGGTGACCCGCTCGATGTGG CGGTCCGGGTCGACGGTGTGGCGCGTGGCGGGGTAGTCGGCGA ACGCGGCGGCGAGGGTGCGTACGGCCCGGGGGACGTCGTCGCG GGTGGCGAGGCGCACCGTGGGCTTGTACTCGGTCATGGTGGCCT GCAGAGTCGCTCTGTGTTCGAGGCCACACGCGTCACCTTAATAT GCGAAGTGGACCTGGGACCGCGCCGCCCCGACTGCATCTGCGTG TTTTCGCCAATGACAAGACGCTGGGCGGGGTTTGTGTCATCATA GAACTAAAGACATGCAAATATATTTCTTCCGGGGACACCGCCAG CAAACGCGAGCAACGGGCCACGGGGATGAAGCAGCTGCGCCAC TCCCTGAAGATCCATCGTCTCCTAACAAGTTACATCACTCCTGCC CTTCCTCACCCTCATCTCCATCACCTCCTTCATCTCCGTCATCTCC GTCATCACCCTCCGCGGCAGCCCCTTCCACCATAGGTGGAAACC AGGGAGGCAAATCTACTCCATCGTCAAAGCTGCACACAGTCACC CTGATATTGCAGGTAGGAGCGGGCTTTGTCATAACAAGGTCCTT 2025202995   29 Apr 2025 AATCGCATCCTTCAAAACCTCAGCAAATATATGAGTTTGTAAAA AGACCATGAAATAACAGACAATGGACTCCCTTAGCGGGCCAGG TTGTGGGCCGGGTCCAGGGGCCATTCCAAAGGGGAGACGACTC AATGGTGTAAGACGACATTGTGGAATAGCAAGGGCAGTTCCTCG CCTTAGGTTGTAAAGGGAGGTCTTACTACCTCCATATACGAACA CACCGGCGACCCAAGTTCCTTCGTCGGTAGTCCTTTCTACGTGAC TCCTAGCCAGGAGAGCTCTTAAACCTTCTGCAATGTTCTCAAATT TCGGGTTGGAACCTCCTTGACCACGATGCTTTCCAAACCACCCTC CTTTTTTGCGCCTGCCTCCATCACCCTGACCCCCGCTGCGCGGGG GCACGTCAGGCTCACCATCTGGGCCGCCTTCTTGGTGGTATTCA AAATAATCGGCTTCCCCTACAGGGTGGAAAAATGGCCTTCTACC TGGAGGGGGCCTGCGCGGTGGAGACCCGGATGATGATGACTGA CTACTGGGACTCCTGGGCCTCTTTTCTCCACGTCCACGACCTCTC CCCCTGGCTCTTTCACGACTTCCCCCCCTGGCTCTTTCACGTCCT CTACCCCGGCGGCCTCCACTACCTCCTCGACCCCGGCCTCCACTA CCTCCTCGACCCCGGCCTCCACTGCCTCCTCGACCCCGGCCTCCA CCTCCTGCTCCTGCCCCTCCCGCTCCTGCTCCTGCTCCTGTTCCAC CGTGGGTCCCTTTGCAGCCAATGCAACTTGGACGTTTTTGGGGTC TCCGGACACCATCTCTATGTCTTGGCCCTGATCCTGAGCCGCCCG GGGCTCCTGGTCTTCCGCCTCCTCGTCCTCGTCCTCTTCCCCGTC CTCGTCCATGTGCCATGATGGCGGCCTGCAGCTGTGTTCGAGGC CGCGCGTGTCACCTTAATATGCGAAGTGGACCTGGGACCGCGCC GCCCCGACTGCATCTGCGTGTTCGAGTTCGCCAATGACAAGACG CTGGGCGGGGAGATCCCCCTTATTAACCCTAAACGGGTAGCATA TGCTTCCCGGGTAGTAGTATATACTATCCAGACTAACCCTAATTC AATAGCATATGTTACCCAACGGGAAGCATATGCTATCGAATTAG GGTTAGTAAAAGGGTCCTAAGGAACAGCGATCTGGATAGCATAT GCTATCCTAATCTATATCTGGGTAGCATATGCTATCCTAATCTAT ATCTGGGTAGCATAGGCTATCCTAATCTATATCTGGGTAGCATAT GCTATCCTAATCTATATCTGGGTAGTATATGCTATCCTAATTTAT ATCTGGGTAGCATAGGCTATCCTAATCTATATCTGGGTAGCATAT GCTATCCTAATCTATATCTGGGTAGTATATGCTATCCTAATCTGT ATCCGGGTAGCATATGCTATCCTCATGCATATACAGTCAGCATA TGATACCCAGTAGTAGAGTGGGAGTGCTATCCTTTGCATATGCC GCCACCTCCCAAGGAGATCTGTCGACATCGATGGGCGCGGGTGT ACACTCCGCCCATCCCGCCCCTAACTCCGCCCAGTTCCGCCCATT CTCCGCCTCATGGCTGACTAATTTTTTTTATTTATGCAGAGGCCG AGGCCGCCTCGGCCTCTGAGCTATTCCAGAAGTAGTGAGGAGGC TTTTTTGGAGGCCTAGGCTTTTGCAAAAAGCTAATTCGGCGTAAT CTGCTGCTTGCAAACAAAAAAACCACCGCTACCAGCGGTGGTTT GTTTGCCGGATCAAGAGCTACCAACTCTTTTTCCGAAGGTAACT GGCTTCAGCAGAGCGCAGATACCAAATACTGTCCTTCTAGTGTA GCCGTAGTTAGGCCACCACTTCAAGAACTCTGTAGCACCGCCTA CATACCTCGCTCTGCTGAAGCCAGTTACCAGTGGCTGCTGCCAG TGGCGATAAGTCGTGTCTTACCGGGTTGGACTCAAGAGATAGTT ACCGGATAAGGCGCAGCGGTCGGGCTGAACGGGGGGTTCGTGC ACACAGCCCAGCTTGGAGCGAACGACCTACACCGAACTGAGAT ACCTACAGCGTGAGCTATGAGAAAGCGCCACGCTTCCCGAAGG GAGAAAGGCGGACAGGTATCCGGTAAGCGGCAGGGTCGGAACA GGAGAGCGCACGAGGGAGCTTCCAGGGGGAAACGCCTGGTATC TTTATAGTCCTGTCGGGTTTCGCCACCTCTGACTTGAGCGTCGAT 2025202995   29 Apr 2025 TTTTGTGATGCTCGTCAGGGGGGCGGAGCCTATGGAAAAACGCC AGCAACGCAAGCTAGAGTTTAAACTTGACAGATGAGACAATAA CCCTGATAAATGCTTCAATAATATTGAAAAAGGAAAAGTATGAG TATTCAACATTTCCGTGTCGCCCTTATTCCCTTTTTTGCGGCATTT TGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTAAA AGATGCAGAAGATCACTTGGGTGCGCGAGTGGGTTACATCGAAC TGGATCTCAACAGCGGTAAGATCCTTGAGAGTTTTCGCCCCGAA GAACGTTTCCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGC GCGGTATTATCCCGTATTGATGCCGGGCAAGAGCAACTCGGTCG CCGCATACACTATTCTCAGAATGACTTGGTTGAATACTCACCAG TCACAGAAAAGCATCTTACGGATGGCATGACAGTAAGAGAATTA TGCAGTGCTGCCATAACCATGAGTGATAACACTGCGGCCAACTT ACTTCTGACAACTATCGGAGGACCGAAGGAGCTAACCGCTTTTT TGCACAACATGGGGGATCATGTAACTCGCCTTGATCGTTGGGAA CCGGAGCTGAATGAAGCCATACCAAACGACGAGCGTGACACCA CGATGCCTGTAGCAATGGCAACAACGTTGCGAAAACTATTAACT GGCGAACTACTTACTCTAGCTTCCCGGCAACAACTAATAGACTG GATGGAGGCGGATAAAGTTGCAGGACCACTTCTGCGCTCGGCAC TTCCGGCTGGCTGGTTTATTGCTGATAAATCAGGAGCCGGTGAG CGTGGGTCACGCGGTATCATTGCAGCACTGGGGCCGGATGGTAA GCCCTCCCGTATCGTAGTTATCTACACTACGGGGAGTCAGGCAA CTATGGATGAACGAAATAGACAGATCGCTGAGATAGGTGCCTCA CTGATTAAGCATTGGTAAGGATAAATTTCTGGTAAGGAGGACAC GTATGGAAGTGGGCAAGTTGGGGAAGCCGTATCCGTTGCTGAAT CTGGCATATGTGGGAGTATAAGACGCGCAGCGTCGCATCAGGCA tttttttctgcgccAAtgcAAAAAggccAtccgtcAggAtggcc TTTCGGCATAACTAGTGAGGCTCCGGTGCCCGTCAGTGGGCAGA GCGCACATCGCCCACAGTCCCCGAGAAGTTGGGGGGAGGGGTC GGCAATTGAACCGGTGCCTAGAGAAGGTGGCGCGGGGTAAACT GGGAAAGTGATGTCGTGTACTGGCTCCGCCTTTTTCCCGAGGGT GGGGGAGAACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTCT TTTTCGCAACGGGTTTGCCGCCAGAACACAGGTAAGTGCCGTGT GTGGTTCCCGCGGGCCTGGCCTCTTTACGGGTTATGGCCCTTGCG TGCCTTGAATTACTTCCACCTGGCTGCAGTACGTGATTCTTGATC CCGAGCTTCGGGTTGGAAGTGGGTGGGAGA.GTTCGAGGCCTTGC GCTTAAGGAGCCCCTTCGCCTCGTGCTTGAGTTGAGGCCTGGCC TGGGCGCTGGGGCCGCCGCGTGCGAATCTGGTGGCACCTTCGCG CCTGTCTCGCTGCTTTCGA.TAAGTCTCTAGCCATTTAAAATTTTT GATGA.CCTGCTGCGA.CGCTTTTTTTCTGGCAAGATAGTCTTGTAA ATGCGGGCCAAGACGATCTGCACACTGGTATTTCGGTTTTTGGG GCCGCGGGCGGCGACGGGGCCCGTGCGTCCCAGCGCACATGTTC GGCGAGGCGGGGCCTGCGAGCGCGGCCACCGAGAATCGGACGG GGGTAGTCTCAAGCTGGCCGGCCTGCTCTGGTGCCTGGCCTCGC GCCGCCGTGTATCGCCCCGCCCTGGGCGGCAAGGCTGGCCCGGT CGGCACCAGTTGCGTGAGCGGAAAGATGGCCGCTTCCCGGCCCT GCTGCAGGGAGCTCAAAATGGAGGA.CGCGGCGCTCGGGAGAGC GGGCGGGTGAGTCACCCACACAAAGGAAAAGGGCCTTTCCGTC CTCAGCCGTCGCTTCATGTGACTCCACGGA.GTACCGGGCGCCGT CCAGGCACCTCGATTAGTTCTCGAGCTTTTGGAGTACGTCGTCTT TAGGTTGGGGGGAGGGGTTTTATGCGATGGAGTTTCCCCACACT GAGTGGGTGGAGACTGAAGTTAGGCCAGCTTGGCACTTGATGTA 2025202995   29 Apr 2025 ATTCTCCTTGGAATTTGCCCTTTTTGAGTTTGGATCTTGGTTCATT CTCAAGCCTCAGACAGTGGTTCAAAGTTTTTTTCTTCCATTTCAG GTGTCGTGAAA 15 Va-1 MKSLRVLLVILWLQLSWVWSQQKEVEQNSGPLSVPEGAIASLNCT YSDRGSQSFFWYRQYSGKSPELIMSIYSNGDKEDGRFTAQLNKASQ YVSLLIRDSQPSDSATYLCAVNVPLSYQLTFGKGTKLSVIP 16 vp-i MLSLLLLLLGLGSVFSAVISQKPSRDICQRGTSLTIQCQVDSQVTMM FWYRQQPGQSLTLIATANQGSEATYESGFVIDKFPISRPNLTFSTLTV SNMSPEDSSIYLCSVAGTIDEQYFGPGTRLTVTE 17 Ig Ck RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNA LQS GNS QES VTEQDSKDSTYSLS STLTLS KADYEKHKV YACE VTHQ GLSSPVTKSFNRGEC 18 IgG-CH-la ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGAL TSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTK VDKKVEPKSC 19 WinZip-Bl SVDELQAEVDQLQDENYALKTKVAQLRKKVEKLAS 20 WinZip-A2 TVAQLRERVKTLRAQNYELESEVQRLREQVAQLAS 21 HLA-DRA EFDAPSPLPETTENVVCALGLTVGLVGIIIGTIFII 22 HLA-DRB1 RARSESAQSKMLSGVGGFVLGLLFLGAGLFI 23 CD-28 RSKRSRLLHSDYMNMTPRRPGPTRKHYQPYAPPRDFAAYRS 24 CD3^ RVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPE MGGKPQRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHD GLYQGLSTATKDTYDALHMQALPPR 25 NLV peptide NLVPMVATV 26 PWH3O8 QKEVEQNSGPLSVPEGAIASLNCTYSDRGSQSFFWYRQYSGKSPELI MSIYSNGDKEDGRFTAQLNKASQYVSLLIRDSQPSDSATYLCAVNV PLSYQLTFGKGTKLSVIPNRTVAAPSVFIFPPSDEQLKSGTASVVCLL NNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLS KADYEKHKVYACEVTHQGLSSPVTKSFNRGECGSGEFDAPSPLPET TENVVCALGLTVGLVGIIIGTIFIIRSKRSRLLHSDYMNMTPRRPGPT RKHYQPYAPPRDFAAYRSRVKFSRSADAPAYQQGQNQLYNELNLG RREEYDVLDKRRGRDPEMGGKPQRRKNPQEGLYNELQKDKMAEA YSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR 27 PWH295 SAVISQKPSRDICQRGTSLTIQCQVDSQVTMMFWYRQQPGQSLTLI ATANQGSEATYESGFVIDKFPISRPNLTFSTLTVSNMSPEDSSIYLCS VAGTIDEQYFGPGTRLTVTEGGSGGASTKGPSVFPLAPSSKSTSGGT AALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSV VTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCGSGRARSESAQ SKMLSGVGGFVLGLLFLGAGLFIYFRSKRSRLLHSDYMNMTPRRPG PTRKHYQPYAPPRDFAAYRSRVKFSRSADAPAYQQGQNQLYNELN LGRREEYDVLDKRRGRDPEMGGKPQRRKNPQEGLYNELQKDKMA EAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR 28 PWH3O3 SAVISQKPSRDICQRGTSLTIQCQVDSQVTMMFWYRQQPGQSLTLI ATANQGSEATYESGFVIDKFPISRPNLTFSTLTVSNMSPEDSSIYLCS VAGTIDEQYFGPGTRLTVTESSASTKGPSVFPLAPSSKSTSGGTAAL GCLVKD YFPEPVTVS WNS GALTS GVHTFPAVLQS S GLYSLS S VVT V PSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCGSGRARSESAQSKM LSGVGGFVLGLLFLGAGLFIYFRSKRSRLLHSDYMNMTPRRPGPTR KHYQPYAPPRDFAAYRSRVKFSRSADAPAYQQGQNQLYNELNLGR 2025202995   29 Apr 2025 REEYDVLDKRRGRDPEMGGKPQRRKNPQEGLYNELQKDKMAEAY SEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR 29 PWH305 SAVISQKPSRDICQRGTSLTIQCQVDSQVTMMFWYRQQPGQSLTLI ATANQGSEATYESGFVIDKFPISRPNLTFSTLTVSNMSPEDSSIYLCS VAGTIDEQYFGPGTRLTVTESSGASAPTLFPLVSCENSPSDTSSVAV GCLAQDFLPDSITFSWKYKNNSDISSTRGFPSVLRGGKYAATSQVLL PS KD VMQGTDEHVVCKVQHPNGNKEKNVPLPVGS GRARSES AQS KMLSGVGGFVLGLLFLGAGLFIYFRSKRSRLLHSDYMNMTPRRPGP TRKHYQPYAPPRDFAAYRSRVKFSRSADAPAYQQGQNQLYNELNL GRREEYDVLDKRRGRDPEMGGKPQRRKNPQEGLYNELQKDKMAE AYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR 30 Va-2 QKEVEQNSGPLSVPEGAIASLNCTYSDRGSQSFFWYRQYSGKSPELI MSIYSNGDKEDGRFTAQLNKASQYVSLLIRDSQPSDSATYLCAVNV PLSYQLTFGKGTKLSVIPN 31 V0-2 SAVISQKPSRDICQRGTSLTIQCQVDSQVTMMFWYRQQPGQSLTLI ATANQGSEATYESGFVIDKFPISRPNLTFSTLTVSNMSPEDSSIYLCS VAGTIDEQYFGPGTRLTVTE 32 IgG-CH-lb SSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSG ALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSN TKVDKKVEPKSC 33 IgM CH-1 SSGASAPTLFPLVSCENSPSDTSSVAVGCLAQDFLPDSITFSWKYKN NSDISSTRGFPSVLRGGKYAATSQVLLPSKDVMQGTDEHVVCKVQ HPNGNKEKNVPLPV 34 HLA-DRB2 RARSESAQSKMLSGVGGFVLGLLFLGAGLFIYF 35 PWH3O8 nucleic acid sequence CAGAAGGAGGTGGAGCAGAATTCTGGACCCCTCAGTGTTCCAGA GGGAGCCATTGCCTCTCTCAACTGCACTTACAGTGACCGAGGTT CCCAGTCCTTCTTCTGGTACAGACAATATTCTGGGAAAAGCCCT GAGTTGATAATGTCCATATACTCCAATGGTGACAAAGAAGATGG AAGGTTTACAGCACAGCTCAATAAAGCCAGCCAGTATGTTTCTC TGCTCATCAGAGACTCCCAGCCCAGTGATTCAGCCACCTACCTC TGTGCCGTGAACGTCCCCTTGAGTTACCAACTCACTTTCGGGAA GGGGACCAAACTCTCGGTCATACCAAATAGAACTGTTGCGGCGC CATCAGTGTTCATCTTTCCCCCTAGCGACGAGCAGCTGAAGAGT GGCACAGCTTCCGTGGTCTGCCTGCTGAACAATTTCTACCCCCG GGAAGCCAAGGTGCAGTGGAAAGTCGATAACGCTCTGCAGTCT GGAAATAGTCAGGAGTCAGTGACTGAACAGGACAGCAAGGATT CCACCTATTCTCTGAGCTCCACCCTGACACTGTCTAAAGCAGACT ACGAGAAGCACAAAGTCTATGCCTGTGAAGTCACTCACCAGGGT CTGTCTTCACCAGTCACCAAATCCTTCAATAGGGGGGAATGCGG CAGTGGTGAGTTTGATGCTCCAAGCCCTCTCCCAGAGACTACAG AGAACGTGGTGTGTGCCCTGGGCCTGACTGTGGGTCTGGTGGGC ATCATTATTGGGACCATCTTCATCATCAGGAGTAAGAGGAGCAG GCTCCTGCACAGTGACTACATGAACATGACTCCCCGCCGCCCCG GGCCCACCCGCAAGCATTACCAGCCCTATGCCCCACCACGCGAC TTCGCAGCCTATCGCTCCAGAGTGAAGTTCAGCAGGAGCGCAGA CGCCCCCGCGTACCAGCAGGGCCAGAACCAGCTCTATAACGAGC TCAATCTAGGACGAAGAGAGGAGTACGATGTTTTGGACAAGAG ACGTGGCCGGGACCCTGAGATGGGGGGAAAGCCGCAGAGAAGG AAGAACCCTCAGGAAGGCCTGTACAATGAACTGCAGAAAGATA AGATGGCGGAGGCCTACAGTGAGATTGGGATGAAAGGCGAGCG CCGGAGGGGCAAGGGGCACGATGGCCTTTACCAGGGTCTCAGT 2025202995   29 Apr 2025 ACAGCCACCAAGGACACCTACGACGCCCTTCACATGCAGGCCCT GCCCCCTCGC 36 PWH295 nucleic acid sequence AGTGCTGTCATCTCTCAAAAGCCAAGCAGGGATATCTGTCAACG TGGAACCTCCCTGACGATCCAGTGTCAAGTCGATAGCCAAGTCA CCATGATGTTCTGGTACCGTCAGCAACCTGGACAGAGCCTGACA CTGATCGCAACTGCAAATCAGGGCTCTGAGGCCACATATGAGAG TGGATTTGTCATTGACAAGTTTCCCATCAGCCGCCCAAACCTAA CATTCTCAACTCTGACTGTGAGCAACATGAGCCCTGAAGACAGC AGCATATATCTCTGCAGCGTTGCCGGGACTATCGACGAGCAGTA CTTCGGGCCGGGCACCAGGCTCACGGTCACAGAGGGAGGATCT GGTGGAGCTTCTACAAAAGGGCCAAGCGTGTTCCCACTGGCACC CAGCTCCAAGTCAACCAGCGGAGGAACAGCCGCTCTGGGATGC CTGGTGAAAGACTACTTCCCAGAGCCCGTGACCGTCTCCTGGAA CTCTGGGGCCCTGACAAGCGGTGTGCACACTTTTCCTGCTGTCCT GCAGTCTAGTGGGCTGTACTCCCTGTCAAGCGTGGTCACTGTGC CATCCTCTAGTCTGGGTACTCAGACCTATATCTGCAACGTGAATC ACAAGCCTAGCAATACCAAAGTGGACAAGAAAGTCGAACCAAA GTCCTGTGGCAGTGGTAGAGCACGGTCTGAATCTGCACAGAGCA AGATGCTGAGTGGAGTCGGGGGCTTTGTGCTGGGCCTGCTCTTC CTTGGGGCCGGGCTGTTCATCTACTTCAGGAGTAAGAGGAGCAG GCTCCTGCACAGTGACTACATGAACATGACTCCCCGCCGCCCCG GGCCCACCCGCAAGCATTACCAGCCCTATGCCCCACCACGCGAC TTCGCAGCCTATCGCTCCAGAGTGAAGTTCAGCAGGAGCGCAGA CGCCCCCGCGTACCAGCAGGGCCAGAACCAGCTCTATAACGAGC TCAATCTAGGACGAAGAGAGGAGTACGATGTTTTGGACAAGAG ACGTGGCCGGGACCCTGAGATGGGGGGAAAGCCGCAGAGAAGG AAGAACCCTCAGGAAGGCCTGTACAATGAACTGCAGAAAGATA AGATGGCGGAGGCCTACAGTGAGATTGGGATGAAAGGCGAGCG CCGGAGGGGCAAGGGGCACGATGGCCTTTACCAGGGTCTCAGT ACAGCCACCAAGGACACCTACGACGCCCTTCACATGCAGGCCCT GCCCCCTCGC 37 PWH3O3 nucleic acid sequence AGTGCTGTCATCTCTCAAAAGCCAAGCAGGGATATCTGTCAACG TGGAACCTCCCTGACGATCCAGTGTCAAGTCGATAGCCAAGTCA CCATGATGTTCTGGTACCGTCAGCAACCTGGACAGAGCCTGACA CTGATCGCAACTGCAAATCAGGGCTCTGAGGCCACATATGAGAG TGGATTTGTCATTGACAAGTTTCCCATCAGCCGCCCAAACCTAA CATTCTCAACTCTGACTGTGAGCAACATGAGCCCTGAAGACAGC AGCATATATCTCTGCAGCGTTGCCGGGACTATCGACGAGCAGTA CTTCGGGCCGGGCACCAGGCTCACGGTCACAGAGTCTAGCGCTT CTACAAAAGGGCCAAGCGTGTTCCCACTGGCACCCAGCTCCAAG TCAACCAGCGGAGGAACAGCCGCTCTGGGATGCCTGGTGAAAG ACTACTTCCCAGAGCCCGTGACCGTCTCCTGGAACTCTGGGGCC CTGACAAGCGGTGTGCACACTTTTCCTGCTGTCCTGCAGTCTAGT GGGCTGTACTCCCTGTCAAGCGTGGTCACTGTGCCATCCTCTAGT CTGGGTACTCAGACCTATATCTGCAACGTGAATCACAAGCCTAG CAATACCAAAGTGGACAAGAAAGTCGAACCAAAGTCCTGTGGC AGTGGTAGAGCACGGTCTGAATCTGCACAGAGCAAGATGCTGA GTGGAGTCGGGGGCTTTGTGCTGGGCCTGCTCTTCCTTGGGGCC GGGCTGTTCATCTACTTCAGGAGTAAGAGGAGCAGGCTCCTGCA CAGTGACTACATGAACATGACTCCCCGCCGCCCCGGGCCCACCC GCAAGCATTACCAGCCCTATGCCCCACCACGCGACTTCGCAGCC 2025202995   29 Apr 2025 TATCGCTCCAGAGTGAAGTTCAGCAGGAGCGCAGACGCCCCCGC GTACCAGCAGGGCCAGAACCAGCTCTATAACGAGCTCAATCTAG GACGAAGAGAGGAGTACGATGTTTTGGACAAGAGACGTGGCCG GGACCCTGAGATGGGGGGAAAGCCGCAGAGAAGGAAGAACCCT CAGGAAGGCCTGTACAATGAACTGCAGAAAGATAAGATGGCGG AGGCCTACAGTGAGATTGGGATGAAAGGCGAGCGCCGGAGGGG CAAGGGGCACGATGGCCTTTACCAGGGTCTCAGTACAGCCACCA AGGACACCTACGACGCCCTTCACATGCAGGCCCTGCCCCCTCGC 38 PWH305 nucleic acid sequence AGTGCTGTCATCTCTCAAAAGCCAAGCAGGGATATCTGTCAACG TGGAACCTCCCTGACGATCCAGTGTCAAGTCGATAGCCAAGTCA CCATGATGTTCTGGTACCGTCAGCAACCTGGACAGAGCCTGACA CTGATCGCAACTGCAAATCAGGGCTCTGAGGCCACATATGAGAG TGGATTTGTCATTGACAAGTTTCCCATCAGCCGCCCAAACCTAA CATTCTCAACTCTGACTGTGAGCAACATGAGCCCTGAAGACAGC AGCATATATCTCTGCAGCGTTGCCGGGACTATCGACGAGCAGTA CTTCGGGCCGGGCACCAGGCTCACGGTCACAGAGtctagcggaAGTG CTAGCGCCCCAACCCTTTTCCCCCTCGTCTCCTGTGAGAATTCCC CGTCGGATACGAGCAGCGTGGCCGTTGGCTGCCTCGCACAGGAC TTCCTTCCCGACTCCATCACTTTCTCCTGGAAATACAAGAACAAC TCTGACATCAGCAGCACCCGGGGCTTCCCATCAGTCCTGAGAGG GGGCAAGTACGCAGCCACCTCACAGGTGCTGCTGCCTTCCAAGG ACGTCATGCAGGGCACAGACGAACACGTGGTGTGCAAAGTCCA GCACCCCAACGGCAACAAAGAAAAGAACGTGCCTCTTCCAGGC AGTGGTAGAGCACGGTCTGAATCTGCACAGAGCAAGATGCTGA GTGGAGTCGGGGGCTTTGTGCTGGGCCTGCTCTTCCTTGGGGCC GGGCTGTTCATCTACTTCAGGAGTAAGAGGAGCAGGCTCCTGCA CAGTGACTACATGAACATGACTCCCCGCCGCCCCGGGCCCACCC GCAAGCATTACCAGCCCTATGCCCCACCACGCGACTTCGCAGCC TATCGCTCCAGAGTGAAGTTCAGCAGGAGCGCAGACGCCCCCGC GTACCAGCAGGGCCAGAACCAGCTCTATAACGAGCTCAATCTAG GACGAAGAGAGGAGTACGATGTTTTGGACAAGAGACGTGGCCG GGACCCTGAGATGGGGGGAAAGCCGCAGAGAAGGAAGAACCCT CAGGAAGGCCTGTACAATGAACTGCAGAAAGATAAGATGGCGG AGGCCTACAGTGAGATTGGGATGAAAGGCGAGCGCCGGAGGGG CAAGGGGCACGATGGCCTTTACCAGGGTCTCAGTACAGCCACCA AGGACACCTACGACGCCCTTCACATGCAGGCCCTGCCCCCTCGC 39 P-NR-025 constantconnecting peptide-transmembr ane domains RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNA LQS GNS QES VTEQDSKDSTYSLS STLTLS KADYEKHKV YACE VTHQ GLSSPVTKSFNRGECGSGEFDAPSPLPETTENVVCALGLTVGLVGIII GTIFII 40 P-NR-026 constantconnecting peptide-transmembr ane domains ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGAL TSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTK VDKKVEPKSCGSGRARSESAQSKMLSGVGGFVLGLLFLGAGLFI 41 P-NR-027 constantconnecting SVDELQAEVDQLQDENYALKTKVAQLRKKVEKLASGGCGGEFDA PSPLPETTENVVCALGLTVGLVGIIIGTIFII 2025202995   29 Apr 2025 peptide-transmembr ane domains 42 P-NR-028 constantconnecting peptide-transmembr ane domains TVAQLRERVKTLRAQNYELESEVQRLREQVAQLASGGCGGRARSE SAQSKMLSGVGGFVLGLLFLGAGLFI 43 PWH3O8 constantconnecting peptide-transmembr ane domains RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNA LQS GNS QES VTEQDSKDSTYSLS STLTLS KADYEKHKV YACE VTHQ GLSSPVTKSFNRGECGSGEFDAPSPLPETTENVVCALGLTVGLVGIII GTIFII 44 PWH295 constantconnecting peptide-transmembr ane domains ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGAL TSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTK VDKKVEPKSCGSGRARSESAQSKMLSGVGGFVLGLLFLGAGLFIYF 45 PWH3O3 constantconnecting peptide-transmembr ane domains SSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSG ALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSN TKVDKKVEPKSCGSGRARSESAQSKMLSGVGGFVLGLLFLGAGLFI YF 46 PWH305 constantconnecting peptide-transmembr ane domains SSGASAPTLFPLVSCENSPSDTSSVAVGCLAQDFLPDSITFSWKYKN NSDISSTRGFPSVLRGGKYAATSQVLLPSKDVMQGTDEHVVCKVQ HPNGNKEKNVPLPVGSGRARSESAQSKMLSGVGGFVLGLLFLGAG LFIYF

Claims

1. A method for expressing a functional modified T cell receptor (TCR) in a T cell, the method comprising transfecting at least one nucleic acid encoding a first and a second TCR peptide chain, wherein the first and second peptide chains of the modified TCR self-assemble on the cell surface with each other and not with endogenous TCR peptides also expressed on the T cell surface, wherein the first peptide chain and the second peptide chain each comprises: an extracellular domain, a transmembrane domain, and an intracellular domain, wherein the extracellular domain comprises a variable region, a constant region, and a connecting peptide; wherein the variable region and the constant region are attached via a linker,wherein either a) the constant region of the first peptide chain comprises an Ig-CK domain and the constant region of the second peptide chain comprises an Ig-CH-1 domain, or b) the constant region of the first peptide chain comprises a WinZip-B1 domain and the constant region of the second peptide chain comprises a WinZip-A2 domain; and wherein either 1) the transmembrane domain of the first peptide chain comprises an HLA-DRA domain and the transmembrane domain of the second peptide chain comprises an HLA-DRB domain, or 2) the transmembrane domain of the first peptide chain comprises an HLA-DRB domain and the transmembrane domain of the second peptide chain comprises an HLA-DRA domain.

2. The method of claim 1, wherein the HLA-DRB domain is HLA-DRB1 or HLA-DRB2.

3. The method of claim 1, wherein the variable region of the extracellular domain of the first peptide chain comprises a TCR a chain, and the variable region of the extracellular domain of the second peptide chain comprises a TCR P chain, wherein the a chain and P chain have specificity for an HLA presented peptide.

4. The method of claim 1, wherein the variable region of the extracellular domain of the first peptide chain comprises a TCR P chain, and the variable region of the extracellular domain of the second peptide chain comprises a TCR a chain, wherein the a chain and P chain have specificity for an HLA presented peptide.

5. The method of claim 1, wherein the variable region of the extracellular domain of at least one of the first and second peptide chains comprises an Ig variable domain, wherein the Ig variable domain has specificity for a tumor antigen.2025202995   03 Jun 20266. The method of claim 1, wherein the first peptide chain comprises SEQ ID NO: 17 and SEQ ID NO: 21, and the second peptide chain comprises SEQ ID NO: 18 and SEQ ID NO: 22.

7. The method of claim 1, wherein the first peptide chain comprises SEQ ID NO: 17 and SEQ ID NO: 21, and the second peptide chain comprises SEQ ID NO: 18 and SEQ ID NO: 34.

8. The method of claim 1, wherein the first peptide chain comprises SEQ ID NO: 39.

9. The method of claim 8, wherein the second peptide chain comprises SEQ ID NO: 40.

10. The method of claim 8, wherein the second peptide chain comprises SEQ ID NO: 44.

11. The method of claim 8, wherein the second peptide chain comprises SEQ ID NO: 45.

12. The method of claim 8, wherein the second peptide chain comprises SEQ ID NO: 46.

13. The method of any one of claims 1-12, wherein the first peptide chain comprises:Ig-CK as the constant region;HLA-DRA as the transmembrane domain;and CD28 and CD3Z as the intracellular domain; and wherein the second peptide chain comprises:Ig-CH-1 or Ig-CH-1b as the constant region;HLA-DRB1 or HLA-DRB2 as the transmembrane domain; andCD28 and CD3Z as the intracellular domain.

14. The method of claim 13, wherein the first peptide chain further comprises a TCR variable a domain and the second peptide chain further comprises a TCR variable 0 domain.

15. The method of claim 14, wherein the first peptide chain further comprises SEQ ID NO:30 and the second peptide chain further comprises SEQ ID NO: 31.

16. The method of claim 15, wherein the first peptide chain further comprises a TCR variable 0 domain and the second peptide chain further comprises a TCR variable a domain.2025202995   03 Jun 202617. The method of claim 16, wherein the first peptide chain further comprises SEQ ID NO: 31 and the second peptide chain further comprises SEQ ID NO: 30.

18. A T cell generated by the method of any one of claims 1-17.

19. A method for reducing the occurrence of or treating cancer or a viral infection in a patient in need thereof, the method comprising administering a pharmaceutical composition to the patient, wherein the pharmaceutical composition comprises a therapeutically effective amount of the T cell of claim 18.

20. The method of claim 19, wherein the cancer is selected from the group consisting of bladder cancer, bone cancer, brain cancer, breast cancer, cancer of the central nervous system, cervical cancer, colon cancer, colorectal cancer, esophageal cancer, eye cancer, gall bladder cancer, head and neck cancer, gastric cancer, HIV / AIDS related cancer, kidney cancer, leukemia, liver cancer, lung cancer, lymphoma, melanoma, multiple myeloma, nasopharyngeal cancer, oral cancer, neuroendocrine cancer, ovarian cancer, pancreatic cancer, prostate cancer, retinoblastoma, sarcoma, skin cancer, stomach cancer, testicular cancer, thyroid cancer, uterine cancer, and vaginal cancer.

21. The method of claim 19, wherein the viral infection is caused by a virus from a viral family selected from the group consisting of herpesviridae, adenoviridae, polyomavididae, poxviridae, reoviridae, coronaviridae, picornaviridae, flaviviridae, hepeviridae, togaviridae, filoviridae, paramyxoviridae, pneumoviridae, rhabdoviridae, hantaviridae, and Orthomyxoviridae.

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