Nucleic acid regulatory elements for constitutive gene expression and methods of use

Abstract

This application relates to nucleic acid regulatory elements that can constitutively enhance the expression of genes in various tissues, or tissues in particular including the liver, muscle, and CNS. This application also relates to methods that utilize these regulatory elements and uses of these elements. Expression cassettes and vectors containing these nucleic acid regulatory elements are also disclosed. These nucleic acid regulatory elements are particularly useful for applications using gene therapy.

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit under 35 U.S.C. §119(e) of the earlier filing dates of U.S. Provisional Patent Application No. 63 / 379,138, filed October 11, 2022, and U.S. Provisional Patent Application No. 63 / 496,554, filed April 17, 2023, which are hereby incorporated by reference in their entireties.

[0002] Electronic Sequence Listing Reference The contents of the electronic sequence listing (SeqList-162027-52976.xml; size: 795,449 bytes; and creation date: October 10, 2023) are incorporated herein by reference in their entirety.

[0003] This application relates to nucleic acid regulatory elements that can enhance expression of genes in various tissues, or tissues including the liver, muscle, and CNS in particular. This application also relates to methods that utilize these regulatory elements and uses of these elements. Expression cassettes and vectors containing these nucleic acid regulatory elements are also disclosed. These are particularly useful for applications using gene therapy. [Background technology]

[0004] A promoter is a DNA region at which transcription of a gene is initiated. Because the promoter region controls when and where a gene of interest is expressed within an organism, promoters are important elements for regulating the level and specificity of transgene expression, especially in the context of gene therapy.

[0005] The use of engineered nucleic acid regulatory elements (NAREs) (which may contain various components, including promoters, enhancers, etc.) specifically tailored to a given gene therapy offers various advantages. To begin with, optimized NAREs enable the desired gene expression levels for a particular therapeutic gene. Second, engineered NAREs with increased potency allow for the administration of smaller amounts of gene therapy vectors, thus reducing immune responses and associated safety risks. Third, for some gene therapies, it is desirable for gene expression to be restricted to specific tissue(s). Therefore, the use of nucleic acid regulatory elements with tissue-specific expression can not only limit undesired transgene expression but also promote sustained transgene expression in the tissue(s) or tissue of interest. Such tissue-specific NAREs can be used to eliminate the need for tissue-specific viral capsids used for gene delivery (or can be used in combination with tissue-specific viral capsids). Fourth, selecting an appropriate NARE also allows for control of the kinetics of gene expression, which in turn affects the durability of the gene therapy. Finally, it may be desirable to engineer NAREs of reduced size (without sacrificing strength or specificity) to allow efficient packaging of larger transgene cargoes into viral vectors.

[0006] While efforts have been made to characterize and optimize NARE sequences through traditional low-throughput analysis (rational design) or newer high-throughput methodologies (e.g., MPRA), these approaches still require expensive and time-consuming in vitro optimization. Therefore, more efficient methods for engineering NAREs, as well as nucleic acid regulatory elements with enhanced potency, reduced size, and / or tissue specificity, are needed. Summary of the Invention

[0007] Provided herein are nucleic acid regulatory elements (NAREs) that contain NAREs that are particularly suitable for expression of operably linked sequences (e.g., protein or RNA coding sequences) in specific tissues, including liver, muscle, and the central nervous system. Also provided herein are methods for expressing a transgene operably linked to one or more of the nucleic acid regulatory elements disclosed herein.

[0008] In embodiments, there is provided a polynucleotide sequence comprising a sequence that is at least 80% identical to a NARE sequence provided in any one of Tables 7 to 9. In embodiments, there is provided a polynucleotide sequence comprising a sequence that is at least 90% identical to a NARE sequence provided in any one of Tables 7 to 9. In embodiments, there is provided a polynucleotide comprising a NARE sequence provided in any one of Tables 7 to 9.

[0009] In embodiments, a polynucleotide sequence is provided that comprises a sequence at least 80% identical to a NARE selected from the group consisting of C6, C7, C7b, C9 to C12, C14, C14_L21, C16 to C18, C21 to C32, C34, C37 to C91, C99 to C102, C104 to C108, C110 to C127, C138 to C194, and C202 to C291 (NAREs are listed in Table 9). In embodiments, a polynucleotide sequence is provided that comprises a sequence that is at least 90% identical to a NARE selected from the group consisting of C6, C7, C7b, C9 to C12, C14, C14_L21, C16 to C18, C21 to C32, C34, C37 to C91, C99 to C102, C104 to C108, C110 to C127, C138 to C194, and C202 to C291. In embodiments, polynucleotide sequences are provided that comprise a NARE selected from the group consisting of C6, C7, C7b, C9 to C12, C14, C14_L21, C16 to C18, C21 to C32, C34, C37 to C91, C99 to C102, C104 to C108, C110 to C127, C138 to C194, and C202 to C291.

[0010] In embodiments, a polynucleotide sequence is provided that comprises a sequence that is at least 80% identical to a NARE selected from the group consisting of C21 to C30 (NAREs are listed in Table 9). In embodiments, a polynucleotide sequence is provided that comprises a sequence that is at least 90% identical to a NARE selected from the group consisting of C21 to C30. In embodiments, a polynucleotide sequence is provided that comprises a NARE selected from the group consisting of C21 to C30.

[0011] In embodiments, a polynucleotide sequence is provided that comprises a sequence that is at least 80% identical to a NARE selected from the group consisting of C118 to C127 (NAREs are listed in Table 9). In embodiments, a polynucleotide sequence is provided that comprises a sequence that is at least 90% identical to a NARE selected from the group consisting of C118 to C127. In embodiments, a polynucleotide sequence is provided that comprises a NARE selected from the group consisting of C118 to C127.

[0012] In embodiments, a polynucleotide sequence is provided that comprises a sequence that is at least 80% identical to a NARE selected from the group consisting of C139 to C158 (NAREs are listed in Table 9). In embodiments, a polynucleotide sequence is provided that comprises a sequence that is at least 90% identical to a NARE selected from the group consisting of C139 to C158. In embodiments, a polynucleotide sequence is provided that comprises a NARE selected from the group consisting of C139 to C158.

[0013] In embodiments, a polynucleotide sequence is provided that comprises a sequence that is at least 80% identical to a NARE selected from the group consisting of C183 to C192 (NAREs are listed in Table 9). In embodiments, a polynucleotide sequence is provided that comprises a sequence that is at least 90% identical to a NARE selected from the group consisting of C183 to C192. In embodiments, a polynucleotide sequence is provided that comprises a NARE selected from the group consisting of C183 to C192.

[0014] In embodiments, polynucleotide sequences are provided that comprise a sequence at least 80% identical to a NARE selected from the group consisting of C53 to C58, C63 to C70, C83 to C91, and C99 to C102 (NAREs are listed in Table 9). In embodiments, polynucleotide sequences are provided that comprise a sequence at least 90% identical to a NARE selected from the group consisting of C53 to C58, C63 to C70, C83 to C91, and C99 to C102. In embodiments, polynucleotide sequences are provided that comprise a NARE selected from the group consisting of C53 to C58, C63 to C70, C83 to C91, and C99 to C102.

[0015] In embodiments, polynucleotide sequences are provided that comprise a sequence at least 80% identical to a NARE selected from the group consisting of C53 to C58, C63 to C70, C83 to C91, C99 to 102, and C108 (NAREs are listed in Table 9). In embodiments, polynucleotide sequences are provided that comprise a sequence at least 90% identical to a NARE selected from the group consisting of C53 to C58, C63 to C70, C83 to C91, C99 to 102, and C108. In embodiments, polynucleotide sequences are provided that comprise a NARE selected from the group consisting of C53 to C58, C63 to C70, C83 to C91, C99 to 102, and C108.

[0016] In embodiments, polynucleotide sequences are provided that comprise a sequence at least 80% identical to a NARE selected from the group consisting of C85, C88, C90, C100-102, C108, C200, and C201 (NAREs are listed in Table 9). In embodiments, polynucleotide sequences are provided that comprise a sequence at least 90% identical to a NARE selected from the group consisting of C85, C88, C90, C100-102, C108, C200, and C201. In embodiments, polynucleotide sequences are provided that comprise a NARE selected from the group consisting of C85, C88, C90, C100-102, C108, C200, and C201.

[0017] In embodiments, polynucleotide sequences are provided that comprise a sequence that is at least 80% identical to a NARE selected from the group consisting of C173 to C178, C187, C200, C210, and C218 (NAREs are listed in Table 9). In embodiments, polynucleotide sequences are provided that comprise a sequence that is at least 90% identical to a NARE selected from the group consisting of C173 to C178, C187, C200, C210, and C218. In embodiments, polynucleotide sequences are provided that comprise a NARE selected from the group consisting of C173 to C177, C187, and C218.

[0018] Methods are provided for the constitutive expression of a transgene operably linked to a constitutive NARE disclosed herein.

[0019] In embodiments, polynucleotide sequences are provided that comprise a sequence at least 80% identical to a nucleic acid regulatory element selected from the group consisting of C9 to C11, C21 to C30, C53 to C58, C63 to C70, C83 to C91, C99 to C102, and C108 (NAREs are listed in Table 9). In embodiments, polynucleotide sequences are provided that comprise a sequence at least 90% identical to a nucleic acid regulatory element selected from the group consisting of C9 to C11, C21 to C30, C53 to C58, C63 to C70, C83 to C91, C99 to C102, and C108. In embodiments, polynucleotide sequences are provided that comprise a nucleic acid regulatory element selected from the group consisting of C9 to C11, C21 to C30, C53 to C58, C63 to C70, C83 to C91, C99 to C102, and C108.

[0020] Provided herein are methods for expressing a transgene in a muscle cell, wherein the transgene is operably linked to a NARE disclosed herein, which is particularly suitable for driving expression in muscle.

[0021] In embodiments, polynucleotide sequences are provided that comprise a sequence at least 80% identical to a nucleic acid regulatory element selected from the group consisting of C14, C16, C21, C23, C26, C36), C42, C46, ​​and C47 (NAREs are listed in Table 9). In embodiments, polynucleotide sequences are provided that comprise a sequence at least 90% identical to a nucleic acid regulatory element selected from the group consisting of C14, C16, C21, C23, C26, C36), C42, C46, ​​and C47. In embodiments, polynucleotide sequences are provided that comprise a nucleic acid regulatory element selected from the group consisting of C14, C16, C21, C23, C26, C36, C42, C46, ​​and C47.

[0022] In embodiments, a polynucleotide sequence is provided that comprises a sequence at least 80% identical to a nucleic acid regulatory element selected from the group consisting of C14, C36, C42, C249-C254, C259, and C260 (NAREs are listed in Table 9). In embodiments, a polynucleotide sequence is provided that comprises a sequence at least 90% identical to a nucleic acid regulatory element selected from the group consisting of C14, C36, C42, C249-C254, C259, and C260. In embodiments, a polynucleotide sequence is provided that comprises a nucleic acid regulatory element selected from the group consisting of C14, C36, C42, C249-C254, C259, and C260.

[0023] Provided herein are methods for expressing a transgene in the CNS, wherein the transgene is operably linked to a NARE disclosed herein and is particularly suitable for driving expression in the CNS. Provided herein are methods for expressing a transgene in a neuronal cell, wherein the transgene is operably linked to a NARE disclosed herein and is particularly suitable for driving expression in a neuronal cell.

[0024] Provided herein are polynucleotides comprising a sequence at least 80% identical to a nucleic acid regulatory element selected from the group consisting of C9-C12, C31-C32, C35-C36, C39-C42, C49-C51, and C57-C58 (NAREs are listed in Table 9). Provided herein are polynucleotides comprising a sequence at least 90% identical to a nucleic acid regulatory element selected from the group consisting of C9-C12, C31-C32, C35-C36, C39-C42, C49-C51, and C57-C58. Provided herein are polynucleotides comprising a nucleic acid regulatory element selected from the group consisting of C9-C12, C31-C32, C35-C36, C39-C42, C49-C51, and C57-C58.

[0025] Provided herein are methods for expressing a transgene in hepatocytes (e.g., in the liver), wherein the transgene is operably linked to a NARE disclosed herein and is particularly suitable for driving expression in hepatocytes (e.g., in the liver).

[0026] In embodiments, one or more nucleic acid regulatory elements disclosed herein are operably linked to a transgene.

[0027] In one aspect, a nucleic acid regulatory element (NARE) is provided that comprises: (i) a sequence that is at least 90% identical to any one of SEQ ID NOs: 344-349, 498, (ii) a sequence that is at least 90% identical to any one of SEQ ID NOs: 337, 338, 355, 357, 358, 359, 407, 411, 429-431, 434, 501, 503, or 504, (iii) optionally, a sequence that is at least 90% identical to any one of SEQ ID NOs: 323, 420, or 488, and (iv) optionally, a sequence that is at least 90% identical to SEQ ID NO: 402 or 444. In some embodiments, the NARE comprises (i) a sequence that is at least 95% identical to any one of SEQ ID NOs: 344-349, or 498; (ii) a sequence that is at least 95% identical to any one of SEQ ID NOs: 337, 338, 355, 357, 358, 359, 407, 411, 429-431, 434, 501, 503, or 504; (iii) optionally, a sequence that is at least 95% identical to any one of SEQ ID NOs: 323, 420, 488; and (iv) optionally, a sequence that is at least 95% identical to SEQ ID NO: 402 or 444. In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, or 498; (ii) any one of SEQ ID NOs: 337, 338, 355, 357, 358, 359, 407, 411, 429-431, 434, 501, 503, or 504; (iii) optionally, any one of SEQ ID NOs: 323, 420, 488; and (iv) optionally, SEQ ID NO: 402 or 444.

[0028] In one aspect, a NARE is provided that comprises (i) a sequence that is at least 90% identical to any one of SEQ ID NOs: 381, 384, 392, 393, 394, 395, 396, 397, 400, or 401, (ii) a sequence that is at least 90% identical to SEQ ID NO: 334 or SEQ ID NO: 342, and (iii) a sequence that is at least 90% identical to SEQ ID NO: 426. In some embodiments, the NARE comprises (i) a sequence that is at least 95% identical to any one of SEQ ID NOs: 381, 384, 392, 393, 394, 395, 396, 397, 400, or 401, (ii) a sequence that is at least 95% identical to SEQ ID NO: 334 or SEQ ID NO: 342, and (iii) a sequence that is at least 95% identical to SEQ ID NO: 426. In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 381, 384, 392, 393, 394, 395, 396, 397, 400, or 401, and (ii) SEQ ID NO: 334 or SEQ ID NO: 342, and (iii) SEQ ID NO: 426.

[0029] In one aspect, a NARE is provided that comprises: (i) a sequence that is at least 90% identical to any one of SEQ ID NOs: 344-349, or 498; (ii) a sequence that is at least 90% identical to SEQ ID NO: 334 or SEQ ID NO: 342; (iii) a sequence that is at least 90% identical to any one of SEQ ID NOs: 302-318, 320-322, 324-327, 331, 332, or 487; (iv) optionally, SEQ ID NO: 333; and (v) optionally, a sequence that is at least 90% identical to SEQ ID NO: 319. In some embodiments, the NARE comprises (i) a sequence at least 95% identical to any one of SEQ ID NOs: 344-349, or 498, (ii) a sequence at least 95% identical to SEQ ID NO: 334 or SEQ ID NO: 342, (iii) a sequence at least 95% identical to any one of SEQ ID NOs: 302-318, 320-322, 324-327, 331, 332, or 487, (iv) optionally, SEQ ID NO: 333, and (v) optionally, a sequence at least 95% identical to SEQ ID NO: 319. In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, or 498; (ii) SEQ ID NO: 334 or SEQ ID NO: 342; (iii) any one of SEQ ID NOs: 302-318, 320-322, 324-327, 331, 332, or 487; (iv) optionally, SEQ ID NO: 333; and (v) optionally, SEQ ID NO: 319.

[0030] In some embodiments, the NARE comprises (i) a sequence that is at least 90% identical to any one of SEQ ID NOs: 344-349, or 498, (ii) a sequence that is at least 90% identical to SEQ ID NO: 334 or SEQ ID NO: 342, and (iii) a sequence that is at least 90% identical to any one of SEQ ID NOs: 302-317, 320-322, 324-327, 331, 332, or 487. In some embodiments, the NARE comprises (i) a sequence that is at least 95% identical to any one of SEQ ID NOs: 344-349, or 498, (ii) a sequence that is at least 95% identical to SEQ ID NO: 334 or SEQ ID NO: 342, and (iii) a sequence that is at least 95% identical to any one of SEQ ID NOs: 302-317, 320-322, 324-327, 331, 332, or 487. In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, or 498, (ii) SEQ ID NO: 334 or SEQ ID NO: 342, and (iii) any one of SEQ ID NOs: 302-317, 320-322, 324-327, 331, 332, or 487.

[0031] In some embodiments, the NARE comprises (i) a sequence that is at least 90% identical to SEQ ID NO: 344-349, 498, (ii) a sequence that is at least 90% identical to SEQ ID NO: 334 or 342, and (iii) a sequence that is at least 90% identical to any one of SEQ ID NO: 302-317, 320-322, 324-327, 331, or 332. In some embodiments, the NARE comprises (i) a sequence that is at least 95% identical to SEQ ID NO: 344-349, 498, (ii) a sequence that is at least 95% identical to SEQ ID NO: 334 or 342, and (iii) a sequence that is at least 95% identical to any one of SEQ ID NO: 302-317, 320-322, 324-327, 331, or 332. In some embodiments, the NARE comprises any one of (i) SEQ ID NOs: 344-349, 498, (ii) SEQ ID NO: 334 or 342, and (iii) SEQ ID NOs: 302-317, 320-322, 324-327, 331, or 332.

[0032] In one aspect, a NARE is provided comprising: (i) a sequence that is at least 90% identical to any one of SEQ ID NOs: 344-349, or 498; (ii) a sequence that is at least 90% identical to any one of SEQ ID NOs: 351-356, 499, or 500; (iii) a sequence that is at least 90% identical to any one of SEQ ID NOs: 200, 370, 417-420, 502, 441, 482-485, 489, or 491-496; and (iv) optionally, a sequence that is at least 90% identical to any one of SEQ ID NOs: 444, 452, or 488; (v) optionally, a sequence that is at least 90% identical to SEQ ID NO: 402; and (vi) optionally, SEQ ID NO: 433. In some embodiments, the NARE comprises (i) a sequence at least 95% identical to any one of SEQ ID NOs: 344-349, or 498; (ii) a sequence at least 95% identical to any one of SEQ ID NOs: 351-356, 499, or 500; (iii) a sequence at least 95% identical to any one of SEQ ID NOs: 200, 370, 417-420, 502, 441, 482-485, 489, or 491-496; and (iv) optionally, a sequence at least 95% identical to any one of SEQ ID NOs: 444, 452, or 488; (v) optionally, a sequence at least 95% identical to SEQ ID NO: 402; and (vi) optionally, SEQ ID NO: 433. In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, or 498; (ii) any one of SEQ ID NOs: 351-356, 499, or 500; (iii) any one of SEQ ID NOs: 200, 370, 417-420, 502, 441, 482-485, 489, or 491-496; and (iv) optionally, any one of SEQ ID NOs: 444, 452, or 488; (v) optionally, SEQ ID NO: 402; and (vi) optionally, SEQ ID NO: 433.

[0033] In some embodiments, the NARE comprises (i) a sequence that is at least 90% identical to any one of SEQ ID NOs: 344-349, or 498; (ii) a sequence that is at least 90% identical to any one of SEQ ID NOs: 351-356, 499, or 500; (iii) a sequence that is at least 90% identical to any one of SEQ ID NOs: 200, 370, 417-420, 502, 482-485, 489, or 491-496; and (iv) optionally, a sequence that is at least 90% identical to SEQ ID NO: 444 or 452. In some embodiments, the NARE comprises (i) a sequence that is at least 95% identical to any one of SEQ ID NOs: 344-349, or 498; (ii) a sequence that is at least 95% identical to any one of SEQ ID NOs: 351-356, 499, or 500; (iii) a sequence that is at least 95% identical to any one of SEQ ID NOs: 200, 370, 417-420, 502, 482-485, 489, or 491-496; and (iv) optionally, a sequence that is at least 95% identical to SEQ ID NO: 444 or 452. In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, 498; (ii) any one of SEQ ID NOs: 351-356, 499, or 500; (iii) any one of SEQ ID NOs: 200, 370, 417-420, 502, 482-485, 489, or 491-496; and (iv) optionally, SEQ ID NO: 444 or 452.

[0034] In some embodiments, the NARE comprises (i) a sequence that is at least 90% identical to any one of SEQ ID NOs: 344-349, or 498, (ii) a sequence that is at least 90% identical to any one of SEQ ID NOs: 351-356, 499, or 500, (iii) a sequence that is at least 90% identical to any one of SEQ ID NOs: 200, 417-420, 502, or 485, and (iv) optionally, a sequence that is at least 90% identical to SEQ ID NO: 444 or 452. In some embodiments, the NARE comprises (i) a sequence that is at least 95% identical to any one of SEQ ID NOs: 344-349, or 498, (ii) a sequence that is at least 95% identical to any one of SEQ ID NOs: 351-356, 499, or 500, (iii) a sequence that is at least 95% identical to any one of SEQ ID NOs: 200, 417-420, 502, or 485, and (iv) optionally, a sequence that is at least 95% identical to SEQ ID NO: 444 or 452. In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, 498, (ii) any one of SEQ ID NOs: 351-356, 499, or 500, (iii) any one of SEQ ID NOs: 200, 417-420, 502, or 485, and (iv) optionally, SEQ ID NO: 444 or 452.

[0035] In some embodiments, the NARE comprises (i) a sequence that is at least 90% identical to any one of SEQ ID NOs: 344-349, or 498, (ii) a sequence that is at least 90% identical to any one of SEQ ID NOs: 351-356, 499, or 500, and (iii) a sequence that is at least 90% identical to any one of SEQ ID NOs: 370, 482-484, 489, or 491-496. In some embodiments, the NARE comprises (i) a sequence that is at least 95% identical to any one of SEQ ID NOs: 344-349, or 498, (ii) a sequence that is at least 95% identical to any one of SEQ ID NOs: 351-356, 499, or 500, and (iii) a sequence that is at least 95% identical to any one of SEQ ID NOs: 370, 482-484, 489, or 491-496. In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, 498, (ii) any one of SEQ ID NOs: 351-356, 499, or 500, and (iii) any one of SEQ ID NOs: 370, 482-484, 489, or 491-496.

[0036] In one aspect, a NARE is provided that comprises: (i) a sequence that is at least 90% identical to any one of SEQ ID NOs: 344-349, or 498; (ii) a sequence that is at least 90% identical to SEQ ID NO: 335; and (iii) a sequence that is at least 90% identical to any one of SEQ ID NOs: 294, 295, 296, 299, 323, 328, 329, 330, 407, 501, 430, 431, 503, 434, or 504; and (iv) optionally, a sequence that is at least 90% identical to SEQ ID NO: 444. In some embodiments, the NARE comprises (i) a sequence that is at least 95% identical to any one of SEQ ID NOs: 344-349, or 498, (ii) a sequence that is at least 95% identical to SEQ ID NO: 335, and (iii) a sequence that is at least 95% identical to any one of SEQ ID NOs: 294, 295, 296, 299, 323, 328, 329, 330, 407, 501, 430, 431, 503, 434, or 504, and (iv) optionally, a sequence that is at least 95% identical to SEQ ID NO: 444. In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, or 498, (ii) SEQ ID NO: 335, and (iii) any one of SEQ ID NOs: 294, 295, 296, 299, 323, 328, 329, 330, 407, 501, 430, 431, 503, 434, or 504, and (iv) optionally, SEQ ID NO: 444.

[0037] In some embodiments, the NARE comprises (i) a sequence that is at least 90% identical to any one of SEQ ID NOs: 344-349, or 498, (ii) a sequence that is at least 90% identical to SEQ ID NO: 335, and (iii) a sequence that is at least 90% identical to any one of SEQ ID NOs: 294, 295, 296, 407, 501, 430, 431, 503, 434, or 504, and (iv) a sequence that is at least 90% identical to SEQ ID NO: 444. In some embodiments, the NARE comprises (i) a sequence at least 95% identical to any one of SEQ ID NOs: 344-349, or 498, (ii) a sequence at least 95% identical to SEQ ID NO: 335, and (iii) a sequence at least 95% identical to any one of SEQ ID NOs: 294, 295, 296, 407, 501, 430, 431, 503, 434, or 504, and (iv) a sequence at least 95% identical to SEQ ID NO: 444. In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, or 498, (ii) SEQ ID NO: 335, and (iii) any one of SEQ ID NOs: 294, 295, 296, 407, 501, 430, 431, 503, 434, or 504, and (iv) SEQ ID NO: 444.

[0038] In one aspect, a NARE is provided that comprises (i) a sequence that is at least 90% identical to any one of SEQ ID NOs: 339, 363-369, 378, 379, 382, ​​385, 387-389, 391, 398, or 399, and (ii) a sequence that is at least 90% identical to any one of SEQ ID NOs: 430, 431, or 503. In some embodiments, the NARE comprises (i) a sequence that is at least 95% identical to any one of SEQ ID NOs: 339, 363-369, 378, 379, 382, ​​385, 387-389, 391, 398, or 399, and (ii) a sequence that is at least 95% identical to any one of SEQ ID NOs: 430, 431, or 503. In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 339, 363-369, 378, 379, 382, ​​385, 387-389, 391, 398, or 399, and (ii) any one of SEQ ID NOs: 430, 431, or 503.

[0039] In one aspect, a NARE is provided that comprises a sequence that is at least 90% identical to any one of SEQ ID NOs: 138-161. In some embodiments, the NARE comprises a sequence that is at least 95% identical to any one of SEQ ID NOs: 138-161. In some embodiments, the NARE comprises any one of SEQ ID NOs: 138-161.

[0040] In one aspect, a NARE is provided that comprises (i) a sequence that is at least 90% identical to SEQ ID NO: 298, (ii) a sequence that is at least 90% identical to SEQ ID NO: 444, and (iii) optionally, a sequence that is at least 90% identical to SEQ ID NO: 475. In some embodiments, the NARE comprises (i) a sequence that is at least 95% identical to SEQ ID NO: 298, (ii) a sequence that is at least 95% identical to SEQ ID NO: 444, and (iii) optionally, a sequence that is at least 95% identical to SEQ ID NO: 475. In some embodiments, the NARE comprises (i) SEQ ID NO: 298, (ii) SEQ ID NO: 444, and (iii) optionally, SEQ ID NO: 475.

[0041] In one aspect, a NARE is provided that comprises (i) a sequence that is at least 90% identical to any one of SEQ ID NOs: 339, 380, 383, 386, or 390, (ii) a sequence that is at least 90% identical to SEQ ID NO: 439 or 497, and (iii) optionally, a sequence that is at least 90% identical to SEQ ID NO: 444. In some embodiments, the NARE comprises (i) a sequence that is at least 95% identical to any one of SEQ ID NOs: 339, 380, 383, 386, or 390, (ii) a sequence that is at least 95% identical to SEQ ID NO: 439 or 497, and (iii) optionally, a sequence that is at least 95% identical to SEQ ID NO: 444. In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 339, 380, 383, 386, or 390, (ii) SEQ ID NO: 439 or 497, and (iii) optionally, SEQ ID NO: 444.

[0042] In some embodiments, the NARE comprises (i) a sequence that is at least 90% identical to any one of SEQ ID NOs: 339, 380, 383, 386, or 390, and (ii) a sequence that is at least 90% identical to SEQ ID NO: 439 or 497. In some embodiments, the NARE comprises (i) a sequence that is at least 95% identical to any one of SEQ ID NOs: 339, 380, 383, 386, or 390, and (ii) a sequence that is at least 95% identical to SEQ ID NO: 439 or 497. In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 339, 380, 383, 386, or 390, and (ii) SEQ ID NO: 439 or 497.

[0043] In one aspect, a NARE is provided, comprising: (i) a sequence that is at least 90% identical to any one of SEQ ID NOs: 344-349, or 498; (ii) a sequence that is at least 90% identical to SEQ ID NO: 336; and (iii) a sequence that is at least 90% identical to any one of SEQ ID NOs: 201, 284, 285, 301, 362, 372, 373, 403-406, 408-410, 412, 427, 444, 453-456, 486, or 490. In some embodiments, the NARE comprises (i) a sequence that is at least 95% identical to any one of SEQ ID NOs: 344-349, or 498, (ii) a sequence that is at least 95% identical to SEQ ID NO: 336, and (iii) a sequence that is at least 95% identical to any one of SEQ ID NOs: 201, 284, 285, 301, 362, 372, 373, 403-406, 408-410, 412, 427, 444, 453-456, 486, or 490. In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, or 498, (ii) SEQ ID NO: 336, and (iii) any one of SEQ ID NOs: 201, 284, 285, 301, 362, 372, 373, 403-406, 408-410, 412, 427, 444, 453-456, 486, or 490.

[0044] In one aspect, a NARE is provided that comprises: (i) a sequence that is at least 90% identical to any one of SEQ ID NOs: 374-376; (ii) optionally, a sequence that is at least 90% identical to any one of SEQ ID NOs: 344-349, 498, or 393; (iii) a sequence that is at least 90% identical to any one of SEQ ID NOs: 93-98, 103, 109, 128-136, 195-198, 201, 284, 285, 301, 362, 371, 373, 403-406, 408-410, 412, 417-420, 502, 427, 453-456, 460-474, 486, or 490; and (iv) optionally, a sequence that is at least 90% identical to SEQ ID NO: 443 or 448. In some embodiments, the NARE comprises (i) a sequence at least 95% identical to any one of SEQ ID NOs: 374-376, (ii) optionally, a sequence at least 95% identical to any one of SEQ ID NOs: 344-349, 498, or 393, (iii) a sequence at least 95% identical to any one of SEQ ID NOs: 93-98, 103, 109, 128-136, 195-198, 201, 284, 285, 301, 362, 371, 373, 403-406, 408-410, 412, 417-420, 502, 427, 453-456, 460-474, 486, or 490, and (iv) optionally, a sequence at least 95% identical to SEQ ID NO: 443 or 448. In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 374-376, (ii) optionally any one of SEQ ID NOs: 344-349, 498, or 393, (iii) any one of SEQ ID NOs: 93-98, 103, 109, 128-136, 195-198, 201, 284, 285, 301, 362, 371, 373, 403-406, 408-410, 412, 417-420, 502, 427, 453-456, 460-474, 486, or 490, and (iv) optionally, SEQ ID NO: 443 or 448.

[0045] In some embodiments, the NARE comprises (i) a sequence that is at least 90% identical to any one of SEQ ID NOs: 374-376, and (ii) a sequence that is at least 90% identical to any one of SEQ ID NOs: 93-98, 103, 109, 128-136, 195-198, 201, 284, 285, 301, 362, 371, 373, 403-406, 408-410, 412, 427, 453-456, 460-474, 486, or 490. In some embodiments, the NARE comprises (i) a sequence that is at least 95% identical to any one of SEQ ID NOs: 374-376, and (ii) a sequence that is at least 95% identical to any one of SEQ ID NOs: 93-98, 103, 109, 128-136, 195-198, 201, 284, 285, 301, 362, 371, 373, 403-406, 408-410, 412, 427, 453-456, 460-474, 486, or 490. In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 374-376, and (ii) any one of SEQ ID NOs: 93-98, 103, 109, 128-136, 195-198, 201, 284, 285, 301, 362, 371, 373, 403-406, 408-410, 412, 427, 453-456, 460-474, 486, or 490.

[0046] In some embodiments, the NARE comprises (i) a sequence that is at least 90% identical to any one of SEQ ID NOs: 374-376, and (ii) a sequence that is at least 90% identical to any one of SEQ ID NOs: 201, 284, 285, 301, 362, 371, 373, 403-406, 408-410, 412, 427, 453-456, 486, or 490. In some embodiments, the NARE comprises (i) a sequence that is at least 95% identical to any one of SEQ ID NOs: 374-376, and (ii) a sequence that is at least 95% identical to any one of SEQ ID NOs: 201, 284, 285, 301, 362, 371, 373, 403-406, 408-410, 412, 427, 453-456, 486, or 490. In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 374-376, and (ii) any one of SEQ ID NOs: 201, 284, 285, 301, 362, 371, 373, 403-406, 408-410, 412, 427, 453-456, 486, or 490.

[0047] In some embodiments, the NARE comprises (i) a sequence that is at least 90% identical to any one of SEQ ID NOs: 374-376, and (ii) a sequence that is at least 90% identical to any one of SEQ ID NOs: 93-98, 103, 109, 128-136, 195-198, or 460-474. In some embodiments, the NARE comprises (i) a sequence that is at least 95% identical to any one of SEQ ID NOs: 374-376, and (ii) a sequence that is at least 95% identical to any one of SEQ ID NOs: 93-98, 103, 109, 128-136, 195-198, or 460-474. In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 374-376, and (ii) any one of SEQ ID NOs: 93-98, 103, 109, 128-136, 195-198, or 460-474.

[0048] In some embodiments, the NARE comprises (i) a sequence that is at least 90% identical to any one of SEQ ID NOs: 344-349, 498, or 393, (ii) a sequence that is at least 90% identical to any one of SEQ ID NOs: 374-376, (iii) a sequence that is at least 90% identical to any one of SEQ ID NOs: 417-420, or 502, and (iv) optionally, a sequence that is at least 90% identical to SEQ ID NO: 443 or 448. In some embodiments, the NARE comprises (i) a sequence that is at least 95% identical to any one of SEQ ID NOs: 344-349, 498, or 393, (ii) a sequence that is at least 95% identical to any one of SEQ ID NOs: 374-376, (iii) a sequence that is at least 95% identical to any one of SEQ ID NOs: 417-420, or 502, and (iv) optionally, a sequence that is at least 95% identical to SEQ ID NO: 443 or 448. In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, 498, or 393; (ii) any one of SEQ ID NOs: 374-376; (iii) any one of SEQ ID NOs: 417-420, or 502; and (iv) optionally, SEQ ID NO: 443 or 448.

[0049] In one aspect, a NARE is provided that comprises: (i) a sequence that is at least 90% identical to SEQ ID NO: 478 or 479; (ii) a sequence that is at least 90% identical to SEQ ID NO: 350; (iii) a sequence that is at least 90% identical to any one of SEQ ID NOs: 351-356, 499, or 500; and (iv) a sequence that is at least 90% identical to any one of SEQ ID NOs: 361, 421, 422, 423, 428, 444, or 480. In some embodiments, the NARE comprises (i) a sequence that is at least 95% identical to SEQ ID NO: 478 or 479, (ii) a sequence that is at least 95% identical to SEQ ID NO: 350, (iii) a sequence that is at least 95% identical to any one of SEQ ID NOs: 351-356, 499, or 500, and (iv) a sequence that is at least 95% identical to any one of SEQ ID NOs: 361, 421, 422, 423, 428, 444, or 480. In some embodiments, the NARE comprises (i) SEQ ID NO: 478 or 479, (ii) SEQ ID NO: 350, (iii) any one of SEQ ID NOs: 351-356, 499, or 500, and (iv) any one of SEQ ID NOs: 361, 421, 422, 423, 428, 444, or 480.

[0050] In one aspect, a NARE is provided that comprises (i) a sequence that is at least 90% identical to SEQ ID NO: 377, and (ii) a sequence that is at least 90% identical to any one of SEQ ID NOs: 444, 457, 458, 469, or 470. In some embodiments, the NARE comprises (i) a sequence that is at least 95% identical to SEQ ID NO: 377, and (ii) a sequence that is at least 95% identical to any one of SEQ ID NOs: 444, 457, 458, 469, or 470. In some embodiments, the NARE comprises (i) SEQ ID NO: 377, and (ii) any one of SEQ ID NOs: 444, 457, 458, 469, or 470.

[0051] In one aspect, a NARE is provided that comprises (i) a sequence that is at least 90% identical to any one of SEQ ID NOs: 199, 476, or 477, and (ii) a sequence that is at least 90% identical to SEQ ID NO: 300. In some embodiments, the NARE comprises (i) a sequence that is at least 95% identical to any one of SEQ ID NOs: 199, 476, or 477, and (ii) a sequence that is at least 95% identical to SEQ ID NO: 300. In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 199, 476, or 477, and (ii) SEQ ID NO: 300.

[0052] In one aspect, a NARE is provided that comprises (i) a sequence that is at least 90% identical to SEQ ID NO: 474, (ii) a sequence that is at least 90% identical to SEQ ID NO: 340 or 341, and (iii) optionally, a sequence that is at least 90% identical to SEQ ID NO: 393. In some embodiments, the NARE comprises (i) a sequence that is at least 95% identical to SEQ ID NO: 474, (ii) a sequence that is at least 95% identical to SEQ ID NO: 340 or 341, and (iii) optionally, a sequence that is at least 95% identical to SEQ ID NO: 393. In some embodiments, the NARE comprises (i) SEQ ID NO: 474, (ii) SEQ ID NO: 340 or 341, and (iii) optionally, SEQ ID NO: 393.

[0053] In one aspect, a NARE is provided that comprises a sequence that is at least 90% identical to any one of SEQ ID NOs: 6, 7, 9-12, 14, 16-18, 21-32, 34, 37-91, 99-102, 104-108, 110-127, 138-194, 202-283, or 286-293. In some embodiments, the NARE comprises a sequence that is at least 95% identical to any one of SEQ ID NOs: 6, 7, 9-12, 14, 16-18, 21-32, 34, 37-91, 99-102, 104-108, 110-127, 138-194, 202-283, or 286-293. In some embodiments, the NARE comprises any one of SEQ ID NOs: 6, 7, 9-12, 14, 16-18, 21-32, 34, 37-91, 99-102, 104-108, 110-127, 138-194, 202-283, or 286-293. In some embodiments, the NARE comprises a sequence that is at least 90% identical to any one of SEQ ID NOs: 6, 14, 16, 18, 34, 48, 104-107, 162-172, 179, 180, 183, 184, or 293. In some embodiments, the NARE comprises a sequence that is at least 95% identical to any one of SEQ ID NOs: 6, 14, 16, 18, 34, 48, 104-107, 162-172, 179, 180, 183, 184, or 293. In some embodiments, the NARE comprises any one of SEQ ID NOs: 6, 14, 16, 18, 34, 48, 104-107, 162-172, 179, 180, 183, 184, or 293.

[0054] In one aspect, an expression construct is provided comprising a NARE disclosed herein and an operably linked transgene. In one embodiment, the expression construct further comprises a polyadenylation sequence.

[0055] In one aspect, a vector is provided comprising an expression construct disclosed herein. In one embodiment, the vector is a non-viral vector. In one embodiment, the vector is a viral vector. In one embodiment, the vector is an adeno-associated virus (AAV) vector. In one embodiment, the vector comprises a nucleic acid sequence comprising (i) an expression construct disclosed herein and (ii) one or more inverted terminal repeats (ITRs). In one embodiment, the vector comprises a 5'ITR and a 3'ITR. In one embodiment, the 5'ITR and the 3'ITR are derived from AAV serotype AAV2.

[0056] In one aspect, a cell is provided comprising an expression construct or vector disclosed herein. In some embodiments, the cell is a neuronal cell, a muscle cell, or a liver cell.

[0057] In one aspect, a pharmaceutical composition is provided that includes (i) an expression construct disclosed herein or a vector disclosed herein, and (ii) a pharmaceutically acceptable excipient.

[0058] In one aspect, a method is provided for expressing a transgene in a cell comprising an expression construct disclosed herein or a vector disclosed herein. In one aspect, a method is provided for regulating transgene expression in a cell comprising an expression construct disclosed herein or a vector disclosed herein. In some embodiments, the cell is a neuronal cell, a muscle cell, or a liver cell. In one aspect, a method is provided for treating a disease comprising administering to a subject in need thereof an expression construct disclosed herein, a vector disclosed herein, or a pharmaceutical composition disclosed herein, wherein the expression construct, vector, or pharmaceutical composition comprises a transgene useful for treating the disease. [Brief explanation of the drawings]

[0059] [Figure 1]This diagram shows a bioinformatics pipeline for the design and optimization of a given promoter sequence using AI. The pipeline is divided into two parallel approaches: (i) promoter enhancement, in which all known / annotated enhancer fragments were collected from the ENCODE database and inserted upstream of the promoter sequence; and (ii) saturation mutagenesis, in which all possible point mutations (no indels) were generated in silico for each base pair of the original input promoter sequence. The best candidates from both approaches were then tested in vitro in the desired cell line and their activity recorded by fluorescence. The best in vitro performers from both strategies were then combined by rational design in a final in vitro screen. [Figure 2] Dual reporter design and measurements. A shows the design of the dual reporter constructs. Candidate nucleic acid regulatory elements were cloned upstream (5') of the mClover3 coding sequence. Each construct contains a constant region containing the tdTomato transgene, used as a normalization control. B provides example flow cytometry data obtained with the dual reporter system, in which mClover3 expression in tdTomato+ cells reflects the level of NARE activity. [Figure 3A] Generation of nucleic acid regulatory elements obtained by modification of the CMV enhancer region of the CAG promoter. Figure 3A: Schematic representation of the CAG enhancer modifications performed. [Figure 3B] Generation of nucleic acid regulatory elements obtained by modification of the CMV enhancer region of the CAG promoter. Figure 3B: Comparison of selected CAG-derived nucleic acid regulatory elements. Expression data were obtained by flow cytometry using the dual reporter system shown in Figure 2B. Expression is provided for expression driven by the CAG (C19) promoter in various transfected cell lines. The CAG-derived nucleic acid regulatory elements shown provided up to a four-fold improvement in efficacy in muscle and neuronal cell lines compared to the CAG promoter, while reducing the size of the nucleic acid regulatory element by up to approximately 900 bp. [Figure 3C]Generation of nucleic acid regulatory elements obtained by modification of the CMV enhancer region of the CAG promoter. Figure 3C: Tissue / cell-selective expression of the indicated nucleic acid regulatory elements in various cell lines. Cell line types are indicated as (H) for human or (M) for mouse. [Figure 4A] Generation of nucleic acid regulatory elements obtained by modification of the β-actin promoter region and / or introns of the CAG promoter. Figure 4A: Expression of the indicated nucleic acid regulatory elements in HEK293T cells relative to the CAG promoter in a dual reporter system. [Figure 4B] Figure 4B: Efficacy of the indicated nucleic acid regulatory elements on the CAG promoter in a dual reporter system. The indicated nucleic acid regulatory elements show sequential modifications (from left to right) that improve expression of the reporter transgene. [Figure 5A] In vitro validation of nucleic acid regulatory elements designed using the methods described herein. Figure 5A: Results from the first-generation nucleic acid regulatory elements showed that most enhancer + NARE constructs performed similarly to or better than the parent JeTmd (C6) promoter. In particular, nucleic acid regulatory elements C101 and C124 showed improved efficacy of approximately 30% and 40%, respectively, compared to C6. Similarly, point mutations resulted in performance improvements of between approximately 10% and 30%. Hypermutation of nucleic acid regulatory elements (using either an iterative or greedy approach) disrupted NARE activity in HEK293T cells. Based on the results from the first-generation constructs, a new set of nucleic acid regulatory elements was designed that combined those elements that resulted in the highest in vitro expression (marked with an asterisk). The second generation was tested in HEK293T cells. All nucleic acid regulatory elements showed higher expression compared to the parent C6. In particular, nucleic acid regulatory element C187 resulted in approximately two-fold higher expression compared to the parent C6. Expression levels were examined using a dual reporter system using flow cytometry. [Figure 5B] In vitro validation of nucleic acid regulatory elements designed according to the methods described herein. Figure 5B: Efficacy of third-generation nucleic acid regulatory elements compared to the CMV promoter (C1) and the CAG promoter (C19) as determined in HEK293T cells using a dual reporter system. [Figure 5C] In vitro validation of nucleic acid regulatory elements designed according to the methods described herein. Figure 5C: Potency of selected nucleic acid regulatory elements compared to the CMV promoter (C1) and the CAG promoter (C19) as determined in HEK293T cells using a dual reporter system. [Figure 5D] In vitro validation of nucleic acid regulatory elements designed using the methods described herein. Figure 5D: Potency of selected nucleic acid regulatory elements compared to the CMV promoter (C1), CAG promoter (C19), and JeTmd (C6) promoter as determined in HEK293T cells using a dual reporter system. [Figure 6] In vivo expression of NAREs in muscle. Gastrocnemius muscles of C57BL / 6 mice were transduced with AAV8-eGFP constructs driven by either the reference promoter CAG or the NARE C85 via IM injection at a dose of 5x10 GC / muscle. Gastrocnemius muscles were sectioned 5 weeks after injection, and six consecutive slices were imaged for eGFP fluorescence / expression. [Figure 7A] Efficacy of selected NAREs in muscle cells. Figure 7A: Efficacy of selected synthetic CAG-based dual NAREs compared to the CMV promoter (C1) and the CAG promoter (C19) in C2C12 cells. [Figure 7B] Efficacy of selected NAREs in muscle cells. Figure 7B: Primary human myotubes were transduced with AAV8-miRFP713-WPRE-SV40 polyA containing the indicated NAREs. [Figure 7C]Efficacy of selected NAREs in muscle cells. Figure 7C: Efficacy of the indicated NAREs compared to the CAG promoter using AAV8-eGFP-WPRE3-bGH polyA(C19) in C2C12 myoblasts. [Figure 7D] Efficacy of selected NAREs in muscle cells. Figure 7D: Efficacy of the indicated nucleic acid regulatory elements in C2C12 cells relative to CAG using a dual reporter system in primary human myotubes. C8, C9, C10, and C11 provide an example of a series of sequential modifications that result in a small, ubiquitous NARE, C11, with 5-fold higher activity than CAG in vitro. C8 is the parent ubiquitous promoter (AdML), nucleic acid regulatory element C9 adds an enhancer, nucleic acid regulatory element C10 adds a start site modification to C9, and nucleic acid regulatory element C11 adds an intron to C10. [Figure 8A] Potency of selected NAREs in neuronal cells. Figure 8A: Potency of selected NAREs measured using a dual reporter assay in transfected N2a cells, a mouse neuroblastoma cell line. [Figure 8B] Efficacy of selected NAREs in neuronal cells. Figure 8B: Efficacy of selected hSyn1-derived NAREs in transfected N2a cells compared to the CMV promoter (C1), CAG promoter (C19), and hSyn1_v2 (B5) promoter. [Figure 8C] Potency of selected NAREs in neuronal cells. Figure 8C: Tissue specificity for selected NAREs (relative expression in N2a cells vs. HEK293T cells). [Figure 8D] Efficacy of selected NAREs in neuronal cells. Figure 8D: Efficacy of NSEmin (B2)-derived NAREs compared to the CMV promoter (C1), CAG promoter (C19), and NSEmin promoter (B2) in transfected N2a cells. [Figure 8E]Efficacy of selected NAREs in neuronal cells. Figure 8E: Tissue specificity for selected NAREs (relative expression in N2a cells vs. relative expression in HEK293T cells). [Figure 8F] Efficacy of selected NAREs in neuronal cells. Figure 8F: Relative expression of the NARE-derived mIRFP713 normalized to the synapsin promoter in transduced primary mouse cortical neurons. [Figure 8G] Efficacy of selected NAREs in neuronal cells. Figure 8G: Efficacy of selected NAREs in transfected BE2M17 cells. [Figure 8H] Efficacy of selected NAREs in neuronal cells. Figure 8H: Efficacy of selected NAREs in transfected N2a cells. [Figure 8I] Efficacy of selected NAREs in neuronal cells. Figure 8I: Efficacy of selected NAREs in transfected N2a cells. [Figure 8J] Potency of selected NAREs in neuronal cells. Figure 8J: Relative expression of NAREs in mouse N2A (left bar), human HEK293T (middle bar), and human HuH7 (right bar) cells using a dual reporter assay. [Figure 9A] Expression and specificity of selected NAREs in primary neuronal cultures. Figure 9A: Primary mouse cortical neurons were transduced with AAV9-miRFP713 driven by candidate NAREs at a multiplicity of infection (MOI) of 50,000 on day 4 in vitro. Seven days later, neurons were imaged to assess miRFP713 expression. [Figure 9B] Expression and specificity of selected NAREs in primary neuronal cultures. (Figure 9B) Transduction efficiency was consistent across constructs. At 7 days post infection (DPI), all NAREs resulted in higher miRFP713 expression than synapsin (hSyn) and showed fewer miRFP713-positive astrocytes than CAG. [Figure 9C]Expression and specificity of selected NAREs in primary neuronal cultures. (Figure 9C) Representative images of neuronal specificity by immunocytochemistry (showing miRFP713, NeuN, and GFAP). Arrows indicate miRFP713-negative astrocytes. Scale bar: 50 μm. [Figure 10A] The selected NAREs are highly specific for neurons in vivo. Male C57Bl / 6J mice were intravenously injected with 5e12GC / kg of AAV9-miRFP713 driven by the candidate NAREs. Four weeks later, fluorescence was measured in each organ ex vivo, and collected genomes were measured for qPCR to quantify transduction. Figure 10A shows a representative image of whole brain ex vivo fluorescence, showing higher expression driven by the selected NAREs compared to CAG. [Figure 10B] The selected NARE is highly specific for neurons in vivo. Male C57Bl / 6J mice were intravenously injected with 5e12 GC / kg of AAV9-miRFP713 driven by the candidate NARE. Four weeks later, transduction was quantified by measuring fluorescence in each organ ex vivo and measuring collected genomes for qPCR. (Figure 10B) Peripheral tissue expression normalized to viral genomes shows low off-target expression in the NARE-driven mouse liver and heart. [Figure 10C] The selected NARE is highly specific for neurons in vivo. Male C57Bl / 6J mice were intravenously injected with 5e12 GC / kg of AAV9-miRFP713 driven by the candidate NARE. Four weeks later, transduction was quantified by measuring fluorescence in each organ ex vivo and measuring collected genomes for qPCR. (Figure 10C) Peripheral tissue expression normalized to viral genomes shows low off-target expression in the NARE-driven mouse liver and heart. [Figure 11A]Efficacy of selected nucleic acid regulatory elements in liver cells in vitro. Figure 11A: Many of the nucleic acid regulatory elements shown were more than two-fold more potent than CAG in liver hepatocytes. Many of the nucleic acid regulatory elements shown were more than 30% more potent than CAG in liver hepatocytes, with C31 being 9-fold more potent than CAG. Expression levels were tested using a dual reporter system using flow cytometry and displayed relative to CAG. [Figure 11B] Efficacy of selected nucleic acid regulatory elements in liver cells in vitro. Figure 11B: Primary mouse hepatocytes were transduced with AAV8-miRFP713-WPRE-SV40 polyA containing the indicated nucleic acid regulatory elements. [Figure 12] The nucleic acid regulatory elements C174 and C177 drive sustained gene expression in the liver in vivo. Expression was analyzed 85 days after iv virus injection. DETAILED DESCRIPTION OF THE INVENTION

[0060] Nucleic acid regulatory elements (NAREs), including promoters, are essential components of gene therapy that control the expression level and durability of therapeutic genes. NAREs can, for example, drive cell-specific expression of transgenes independently of capsid selection. Incorporation of stronger NAREs can increase potency and efficacy at lower viral vector doses, thereby potentially reducing safety risks, immune responses, and the cost of vector production. Furthermore, reducing NARE size while maintaining strength and specificity allows for the efficient packaging of larger transgenes or expression cassettes into AAVs. This application provides a library of nucleic acid regulatory elements for improving the safety, efficacy, and durability of therapeutic transgene expression.

[0061] Many NAREs, particularly promoter sequences, have been characterized and optimized through traditional low-throughput analysis (rational design) or newer high-throughput methodologies (e.g., MPRA). However, these approaches still require expensive and time-consuming in vitro optimization. Here, we used an advanced artificial intelligence model to repurpose convolutional neural networks (CNNs) and optimize them to predict NARE potency. A library of nucleic acid regulatory elements was computationally constructed by cloning all known enhancer elements reported in the ENCODE database upstream of strong, small, constitutive promoters. The precise spacing between enhancer elements and promoter sequences that performed particularly well was then optimized. In parallel, in silico saturation mutagenesis was performed, whereby all possible point mutations within the NARE sequence were introduced and those with the best effect on NARE potency were selected. The best performers were then produced and tested in vitro. While most nucleic acid regulatory elements performed better or equivalently to the original promoter, the best enhancer elements and point mutations were selected and combined in a second optimization round. After synthesis and testing of this new set in vitro, enhanced nucleic acid regulatory elements were obtained that exhibited increased potency.

[0062] NARE Provided herein are NAREs that may contain promoters and / or enhancers as part of their sequences. Conventionally, a promoter is defined as a DNA region where transcription is initiated. A promoter contains specific DNA motifs that can be accessed by transcription factors (TFs) and their complexes. On the other hand, an enhancer is defined as a DNA region that amplifies transcription initiation by directly interacting with a target promoter. Similarly, enhancer sequences distal to a target promoter contain DNA motifs that act as binding sites for TFs and cofactors. The term promoter can sometimes be used as a shortened form to refer to a nucleic acid sequence containing multiple regulatory elements. For example, CAG, which contains a CMV enhancer, a β-actin promoter region, and an intron, can be referred to as a promoter. Specifically, the CAG promoter consists of (1) a cytomegalovirus (CMV) early enhancer element, (2) the promoter, the first exon and first intron of the chicken β-actin gene, and (3) the splice acceptor of the rabbit β-globin gene. As used herein, the term "nucleic acid regulatory element" (NARE) can refer to a promoter, defined in the conventional sense, as well as a combination of elements comprising a promoter and / or other nucleic acid regulatory elements that regulate expression of an RNA- or protein-coding sequence operably linked to the element(s). A nucleic acid regulatory element can be, or can include, for example, a promoter, an enhancer, a translation initiation signal, an intron, and / or a splicing enhancer.

[0063] As used herein, the term "NARE" can refer to a promoter, as defined in the conventional sense, as well as a combination of nucleic acid regulatory elements, including promoters and / or other nucleic acid regulatory elements, that regulate expression of a gene operably linked to the element(s). A nucleic acid regulatory element can be, or can include, for example, a promoter, an enhancer, a translation initiation signal, an intron, and / or a splicing enhancer.

[0064] As used herein, "transgene" refers to a gene (particularly the coding sequence of a gene) that is transferred into one or more cells of an organism, for example, using a vector described herein. A transgene can encode a protein or RNA that is normally expressed in the cells of the target organism, or it can encode a protein or RNA from a different organism. A transgene can be integrated into the genome of the target cell or can be present as part of an extrachromosomal expression construct.

[0065] As used herein, "operably linked" refers to a first molecule linked to a second molecule, the molecules being positioned so that the first molecule affects the function of the second molecule. The two molecules may or may not be part of a single, continuous molecule, and may or may not be adjacent. For example, if a NARE regulates the transcription of a transcribable polynucleotide molecule of interest in a cell, the NARE is operably linked to the transcribable polynucleotide molecule. In addition, two portions of a transcriptional regulatory element are operably linked to each other if they are linked such that the transcriptional activation function of one portion is not adversely affected by the presence of the other portion. Two transcriptional regulatory elements may be operably linked to each other via a linker nucleic acid (e.g., an intervening non-coding nucleic acid) or may be operably linked to each other without any intervening nucleotides.

[0066] Provided herein are engineered regulatory elements that can drive transgene expression in a variety of different tissues, including muscle, the central nervous system, and the liver. For example, we have developed a CAG-derived nucleic acid regulatory element that is stronger, smaller, and more potent than the original CAG sequence. The NARE engineering platform described herein has resulted in a large number of nucleic acid regulatory elements that can be used to drive the expression of multiple therapeutic transgenes. This platform, as disclosed herein, has also been applied to different tissues and cell types of interest, including muscle, the central nervous system, and the liver.

[0067] Constructive NARE The present disclosure provides nucleic acid regulatory elements for constitutive expression of an operably linked transgene, i.e., maintaining expression of the transgene at a constant level. Constitutive NAREs can drive expression of an operably linked transgene in various cell types and tissues. As used herein, NAREs beginning with "C" are constitutive NAREs. The constitutive NAREs disclosed herein can be useful, for example, for expressing genes in the liver, muscle, and / or central nervous system.

[0068] Examples of constitutive nucleic acid regulatory elements and their components are shown in Tables 7-9.

[0069] In embodiments, polynucleotide sequences are provided that comprise a sequence at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to a nucleic acid regulatory element provided in Table 7 or 9. In embodiments, polynucleotides are provided that comprise one or more nucleic acid regulatory elements provided in Table 7 or 9. As used herein, the term "identity" refers to the sequence identity between two nucleic acid molecules or polypeptides. Identity can be determined by comparing positions in each sequence that can be aligned for comparison purposes. For example, if a position in a compared nucleotide sequence is occupied by the same base, the molecules are identical at that position. The degree of identity between nucleic acid or amino acid sequences is a function of the number of identical or matching nucleotides or amino acids at shared positions. Methods and computer programs for determining both sequence identity and similarity are publicly available, including, but not limited to, the GCG program package (Devereux et al., Nucleic Acids Research 12:387, 1984), BLASTP, BLASTN, FASTA (Altschul et al., J. Mol. Biol. 215:403 (1990), and the ALIGN program (version 2.0). The well-known Smith-Waterman algorithm may also be used to determine similarity. BLAST programs are publicly available from NCBI and other sources (BLAST Manual, Altschul, et al., NCBI NLM NIH, Bethesda, Md. 20894, BLAST 2.0 at http: / / www.ncbi.nlm.nih.gov / blast / ). These methods take into account various substitutions, deletions, and other modifications when comparing sequences.

[0070] In embodiments, a polynucleotide sequence is provided that comprises a sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to a nucleic acid regulatory element selected from the group consisting of C6, C7, C7b, C9 through C12, C14, C14_L21, C16 through C18, C21 through C32, C34, C37 through C91, C99 through C102, C104 through C108, C110 through C127, C138 through C194, and C202 through C291. In embodiments, polynucleotide sequences are provided that include a nucleic acid regulatory element selected from the group consisting of C6, C7, C7b, C9 through C12, C14, C14_L21, C16 through C18, C21 through C32, C34, C37 through C91, C99 through C102, C104 through C108, C110 through C127, C138 through C194, and C202 through C291.

[0071] In embodiments, there is provided a polynucleotide sequence comprising a sequence at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to a nucleic acid regulatory element selected from the group consisting of C21 to C30. In embodiments, there is provided a polynucleotide sequence comprising a nucleic acid regulatory element selected from the group consisting of C21 to C30.

[0072] In embodiments, there is provided a polynucleotide sequence comprising a sequence at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to a nucleic acid regulatory element selected from the group consisting of C118 to C127. In embodiments, there is provided a polynucleotide sequence comprising a nucleic acid regulatory element selected from the group consisting of C118 to C127.

[0073] In embodiments, there is provided a polynucleotide sequence comprising a sequence at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to a nucleic acid regulatory element selected from the group consisting of C139 to C158. In embodiments, there is provided a polynucleotide sequence comprising a nucleic acid regulatory element selected from the group consisting of C139 to C158.

[0074] In embodiments, there is provided a polynucleotide sequence comprising a sequence at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to a nucleic acid regulatory element selected from the group consisting of C183 to C192. In embodiments, there is provided a polynucleotide sequence comprising a nucleic acid regulatory element selected from the group consisting of C183 to C192.

[0075] In embodiments, there is provided a polynucleotide sequence comprising a sequence at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to a nucleic acid regulatory element selected from the group consisting of C53 to C58, C63 to C70, C83 to C91, and C99 to C102. In embodiments, there is provided a polynucleotide sequence comprising a nucleic acid regulatory element selected from the group consisting of C53 to C58, C63 to C70, C83 to C91, and C99 to C102.

[0076] In embodiments, provided are polynucleotide sequences comprising a sequence at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to a nucleic acid regulatory element selected from the group consisting of C53 to C58, C63 to C70, C83 to C91, C99 to 102, and C108. In embodiments, provided are polynucleotide sequences comprising a nucleic acid regulatory element selected from the group consisting of C53 to C58, C63 to C70, C83 to C91, C99 to 102, and C108.

[0077] In embodiments, provided are polynucleotide sequences comprising a sequence at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to a nucleic acid regulatory element selected from the group consisting of C85, C88, C90, C100-102, and C108. In embodiments, provided are polynucleotide sequences comprising a nucleic acid regulatory element selected from the group consisting of C85, C88, C90, C100-102, and C108.

[0078] In embodiments, there is provided a polynucleotide sequence comprising a sequence at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to a nucleic acid regulatory element selected from the group consisting of C173 to C178, C187, C200, C210, and C218. In embodiments, there is provided a polynucleotide sequence comprising a nucleic acid regulatory element selected from the group consisting of C173 to C177, C187, and C218.

[0079] Provided herein are methods for the constitutive expression of a transgene operably linked to a constitutive nucleic acid regulatory element disclosed herein.

[0080] Provided herein are methods for the constitutive expression of a transgene operably linked to a sequence comprising a sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to a nucleic acid regulatory element provided herein. Provided herein are methods for the constitutive expression of a transgene operably linked to one or more nucleic acid regulatory elements provided herein.

[0081] Provided herein are methods for the constitutive expression of a transgene operably linked to a sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to a nucleic acid regulatory element selected from the group consisting of C6, C7, C7b, C9-C12, C14, C14_L21, C16-C18, C21-C32, C34, C37-C91, C99-C102, C104-C108, C110-C127, C138-C194, and C202-C291. Provided herein are methods for the constitutive expression of a transgene operably linked to a sequence selected from the group consisting of C6, C7, C7b, C9-C12, C14, C14_L21, C16-C18, C21-C32, C34, C37-C91, C99-C102, C104-C108, C110-C127, C138-C194, and C202-C291.

[0082] Nucleic acid regulatory elements for driving gene expression in muscle Nucleic acid regulatory elements particularly suitable for driving expression in muscle are provided herein. Muscle NAREs can be muscle-specific, meaning that they exhibit significantly increased or preferential expression of an operably linked transgene in muscle compared to other tissues.

[0083] Tables 7 or 9 also provide nucleic acid regulatory elements suitable for driving expression in various tissues, including muscle.

[0084] In embodiments, polynucleotide sequences are provided that comprise a sequence at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to a nucleic acid regulatory element selected from the group consisting of C9 to C11, C21 to C30, C53 to C58, C63 to C70, C83 to C91, C99 to C102, and C108. In embodiments, polynucleotide sequences are provided that comprise a nucleic acid regulatory element selected from the group consisting of C9 to C11, C21 to C30, C53 to C58, C63 to C70, C83 to C91, C99 to C102, and C108.

[0085] Provided herein are methods for expressing a transgene in a muscle cell, wherein the transgene is operably linked to a nucleic acid regulatory element disclosed herein, which is particularly suitable for driving expression in muscle.

[0086] Provided herein are methods for expressing a transgene in a muscle cell, wherein the transgene is operably linked to a sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to a nucleic acid regulatory element provided herein. Provided herein are methods for expressing a transgene in a muscle cell, wherein the transgene is operably linked to a nucleic acid regulatory element provided herein.

[0087] NARE for driving gene expression in the central nervous system (CNS) Provided herein are NAREs that are particularly suitable for driving expression in the CNS. CNS NAREs can be CNS-specific, meaning that they exhibit significantly increased or preferential expression of an operably linked transgene in the CNS compared to other tissues. Tables 7 and 9 also provide nucleic acid regulatory elements suitable for driving expression in various tissues, including the CNS. In embodiments, polynucleotide sequences are provided that include a sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to a NARE selected from the group consisting of C14, C16, C21, C23, C26, C36), C42, C46, ​​and C47. In embodiments, a polynucleotide sequence is provided that comprises a NARE selected from the group consisting of C14, C16, C21, C23, C26, C36, C42, C46, ​​and C47.

[0088] In embodiments, provided are polynucleotide sequences comprising a sequence at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to a NARE selected from the group consisting of C14, C36, C42, C249-C254, C259, and C260. In embodiments, provided are polynucleotide sequences comprising a NARE selected from the group consisting of C14, C36, C42, C249-C254, C259, and C260. Provided herein are methods for expressing a transgene in the CNS, wherein the transgene is operably linked to a NARE disclosed herein and is particularly suitable for driving expression in the CNS.

[0089] Provided herein is a method for expressing a transgene in a neuronal cell, wherein the transgene is operably linked to a NARE disclosed herein and is particularly suitable for driving expression in a neuronal cell. Provided herein is a method for expressing a transgene in the CNS, wherein the transgene is operably linked to a sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the nucleic acid regulatory element provided herein. Provided herein is a method for expressing a transgene in the CNS, wherein the transgene is operably linked to the nucleic acid regulatory element provided herein. Provided herein are methods for expressing a transgene in a neural cell, wherein the transgene is operably linked to a sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to a nucleic acid regulatory element provided herein. Provided herein are methods for expressing a transgene in a neural cell, wherein the transgene is operably linked to a nucleic acid regulatory element provided herein.

[0090] In embodiments, the transgene is UPF1 or BDNF.

[0091] to drive gene expression in the liver Provided herein is the NARE that is particularly suitable for driving expression in liver.Liver NARE can be liver-specific, which means that they show significantly increased or preferential expression of operably linked transgene in liver compared with other tissues.Table 7 or 9 also provides the nucleic acid regulatory element that is suitable for driving expression in various tissues, including liver.

[0092] In embodiments, provided are polynucleotide sequences comprising a sequence at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to a nucleic acid regulatory element selected from the group consisting of C9-C12, C31-C32, C35-C36, C39-C42, C49-C51, and C57-C58. Provided herein are polynucleotides comprising a nucleic acid regulatory element selected from the group consisting of C9-C12, C31-C32, C35-C36, C39-C42, C49-C51, and C57-C58.

[0093] Provided herein are methods for expressing a transgene in hepatocytes (e.g., in the liver), wherein the transgene is operably linked to a nucleic acid regulatory element disclosed herein and is particularly suitable for driving expression in hepatocytes (e.g., in the liver).

[0094] Provided herein is a method for expressing a transgene in the liver, wherein the transgene is operably linked to a sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to a nucleic acid regulatory element provided herein. Provided herein is a method for expressing a transgene in the liver, wherein the transgene is operably linked to a nucleic acid regulatory element provided herein.

[0095] In embodiments, the transgene is an ATP7B or ATB7B minigene.

[0096] NARE Qualification Those skilled in the art will understand that certain modifications can be made to the nucleic acid regulatory elements disclosed herein without eliminating the ability of the nucleic acid regulatory element to drive gene expression in the desired tissue / cell type. Various in vitro and in vivo methods for confirming that a modified NARE is still capable of driving gene expression are known in the art, including, but not limited to, the methods used herein. For example, the strength of a NARE can be assessed by operably linking the NARE to a transgene encoding a protein and measuring transgene expression, e.g., by detecting mRNA encoding the protein, or by measuring the presence or activity of the protein, e.g., by ELISA, Western blot, fluorescence, enzymatic activity of the protein, etc.

[0097] Provided herein are NAREs comprising one or more components. Provided herein are NAREs comprising one or more sequence components (or sequence variants thereof) listed in any one of Tables 7-9. Provided herein are NAREs comprising one or more sequence components (or sequence variants thereof) listed in Tables 8 and 9. Provided herein are NAREs comprising one or more components (or sequence variants thereof) of a full-length NARE provided in Table 9. Simply by way of illustration and non-limiting example, provided are NAREs comprising one or more of the components (or sequence variants thereof) of NARE C22 (EH38E2531636-actb-CBh): (1) EH38E2531636, (2) CBA promoter variant 2, and (3) a hybrid intron. In embodiments, provided are NAREs comprising one or more components (or sequence variants thereof) of a full-length NARE provided in Table 9, whereby the components (or sequence variants thereof) are arranged 5' to 3' as shown in Table 9. In embodiments, NAREs are provided that comprise one or more components of a full-length NARE provided in Table 9 (or sequence variants thereof), whereby the components (or sequence variants thereof) are not arranged 5' to 3' as shown in Table 9, but are arranged in a different order.

[0098] In embodiments, in a NARE of Table 7 or 9, one or more of the components are replaced with a different sequence, comprising components (or sequence variants thereof) from different NAREs of Table 7 or 9. Additionally, NAREs comprising components (or sequence variants thereof) from two or more NAREs disclosed in Table 7 or 9 are also contemplated.

[0099] Furthermore, NARE variants are contemplated that contain sequences in addition to the elements of the NAREs disclosed herein (e.g., added to either end of the NARE sequence or inserted within the NARE sequence). Similarly, NARE variants are provided in which specific sequences have been removed from the NAREs disclosed herein (e.g., as terminal or internal deletions). In embodiments, NAREs comprising one or more components are provided without any additional nucleic acid sequence(s) linking the components of the NARE. In embodiments, NAREs comprising one or more components are provided, whereby individual components are connected by additional nucleic acid sequences. These additional nucleic acid sequences may or may not be related to the expression of an operably linked transgene. In embodiments, some of the components are directly linked, while other components are linked to other components via intervening sequences. Thus, variants of the NAREs disclosed in Tables 7 or 9 are contemplated, in which additional sequences have been added between different components. Variants of the NAREs disclosed in Tables 7 or 9 are further contemplated, which disclose the same components of a given NARE in Tables 7 or 9, but differ in the sequence(s) connecting the individual components.

[0100] In some embodiments, the NARE comprises a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to a sequence selected from the group consisting of SEQ ID NOs: 6, 7, 9-12, 14, 16-18, 21-32, 34, 37-91, 99-102, 104-108, 110-127, 138-194, 202-283, 286-293.

[0101] In some embodiments, the NARE comprises a sequence selected from the group consisting of SEQ ID NOs: 6, 7, 9-12, 14, 16-18, 21-32, 34, 37-91, 99-102, 104-108, 110-127, 138-194, 202-283, 286-293.

[0102] In some embodiments, the NARE is (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 344-349, 498; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 337, 338, 355, 357, 358, 359, 407, 501, 411, 429, 430, 431, 503, 434, 504; (iii) optionally, a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 323, 420, 488; and (iv) optionally, a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NOs: 402 or 444.

[0103] In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, 498; (ii) any one of SEQ ID NOs: 337, 338, 355, 357, 358, 359, 407, 501, 411, 429, 430, 431, 503, 434, 504; (iii) optionally, any one of SEQ ID NOs: 323, 420, 488; and (iv) optionally, SEQ ID NO: 402 or 444.

[0104] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 344-349, 498; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 429; and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 444.

[0105] In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, 498, (ii) SEQ ID NO: 429, and (iii) SEQ ID NO: 444.

[0106] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 349, (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NO: 429, and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 444.

[0107] In some embodiments, the NARE comprises (i) SEQ ID NO: 349, (ii) SEQ ID NO: 429, and (iii) SEQ ID NO: 444.

[0108] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 344-349, 498; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 430, 431, 503; and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 444.

[0109] In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, 498, (ii) any one of SEQ ID NOs: 430, 431, 503, and (iii) SEQ ID NO: 444.

[0110] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 349, (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 431, and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 444.

[0111] In some embodiments, the NARE comprises (i) any one of SEQ ID NO: 349, (ii) SEQ ID NO: 431, and (iii) SEQ ID NO: 444.

[0112] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 344-349, 498; or (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 357.

[0113] In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, 498, and (ii) SEQ ID NO: 357.

[0114] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 349, and (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 357.

[0115] In some embodiments, the NARE comprises (i) SEQ ID NO: 349, and (ii) SEQ ID NO: 357.

[0116] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 344-349, 498; or (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 358.

[0117] In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, 498, and (ii) SEQ ID NO: 358.

[0118] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 349, and (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 358.

[0119] In some embodiments, the NARE comprises (i) SEQ ID NO: 349, and (ii) SEQ ID NO: 358.

[0120] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 344-349, 498; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 359.

[0121] In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, 498, and (ii) SEQ ID NO: 359.

[0122] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 349, and (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 359.

[0123] In some embodiments, the NARE comprises (i) SEQ ID NO: 349, and (ii) SEQ ID NO: 359.

[0124] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 344-349, 498; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 411; and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 420.

[0125] In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, 498, (ii) SEQ ID NO: 411, and (iii) SEQ ID NO: 420.

[0126] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 498, (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 411, and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 420.

[0127] In some embodiments, the NARE comprises (i) SEQ ID NO:498, (ii) SEQ ID NO:411, and (iii) SEQ ID NO:420.

[0128] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 344-349, 498; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 407, 434, 501, 504; and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 323.

[0129] In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, 498, (ii) SEQ ID NOs: 407, 434, 501, 504, and (iii) SEQ ID NO: 323.

[0130] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 348; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 407, 434, 501, 504; and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 323.

[0131] In some embodiments, the NARE comprises (i) SEQ ID NO: 348, (ii) any one of SEQ ID NOs: 407, 434, 501, 504, and (iii) SEQ ID NO: 323.

[0132] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 344-349, 498; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 407 or 501; and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 323.

[0133] In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, 498, (ii) SEQ ID NO: 407 or 501, and (iii) SEQ ID NO: 323.

[0134] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 348, (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 407, and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 323.

[0135] In some embodiments, the NARE comprises (i) SEQ ID NO: 348, (ii) SEQ ID NO: 407, and (iii) SEQ ID NO: 323.

[0136] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 344-349, 498; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 434 or 504; and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 323.

[0137] In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, 498, (ii) SEQ ID NO: 434 or 504, and (iii) SEQ ID NO: 323.

[0138] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 348, (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 434, and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 323.

[0139] In some embodiments, the NARE comprises (i) SEQ ID NO: 348, (ii) SEQ ID NO: 434, and (iii) SEQ ID NO: 323.

[0140] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 344-349, 498; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 337; and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 444.

[0141] In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, 498, (ii) SEQ ID NO: 337, and (iii) SEQ ID NO: 444.

[0142] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 344; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 337; and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 444.

[0143] In some embodiments, the NARE comprises (i) SEQ ID NO: 344, (ii) SEQ ID NO: 337, and (iii) SEQ ID NO: 444.

[0144] In some embodiments, the NARE is (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 344-349, 498; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 338; (iii) sequences that are at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 488; and (iv) sequences that are at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 402.

[0145] In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, 498, (ii) SEQ ID NO: 338, (iii) SEQ ID NO: 488, and (iv) SEQ ID NO: 402.

[0146] In some embodiments, the NARE comprises: (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 348; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 338; (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 488; and (iv) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 402.

[0147] In some embodiments, the NARE comprises (i) SEQ ID NO: 348, (ii) SEQ ID NO: 338, (iii) SEQ ID NO: 488, and (iv) SEQ ID NO: 402.

[0148] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 344-349, 498; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 338; and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 444.

[0149] In some embodiments, the NARE comprises (i) SEQ ID NOs: 344-349, 498, (ii) SEQ ID NO: 338, and (iii) SEQ ID NO: 444.

[0150] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 348, (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 338, and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 444.

[0151] In some embodiments, the NARE comprises (i) SEQ ID NO: 348, (ii) SEQ ID NO: 338, and (iii) SEQ ID NO: 444.

[0152] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 381, 384, 392, 393, 394, 395, 396, 397, 400, 401; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 334 or 342; and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 426.

[0153] In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 381, 384, 392, 393, 394, 395, 396, 397, 400, 401, (ii) SEQ ID NO: 334 or 342, and (iii) SEQ ID NO: 426.

[0154] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 381, 384, 392, 393, 394, 395, 396, 397, 400, 401; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 342; and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 426.

[0155] In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 381, 384, 392, 393, 394, 395, 396, 397, 400, 401, (ii) SEQ ID NO: 342, and (iii) SEQ ID NO: 426.

[0156] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 396, (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 334 or 342, and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 426.

[0157] In some embodiments, the NARE comprises (i) SEQ ID NO: 396, and (ii) SEQ ID NO: 334 or 342, and (iii) SEQ ID NO: 426.

[0158] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 396, and (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 342, and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 426.

[0159] In some embodiments, the NARE comprises (i) SEQ ID NO: 396, and (ii) SEQ ID NO: 342, and (iii) SEQ ID NO: 426.

[0160] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 397; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 334 or 342; and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 426.

[0161] In some embodiments, the NARE comprises (i) SEQ ID NO: 397, and (ii) SEQ ID NO: 334 or 342, and (iii) SEQ ID NO: 426.

[0162] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 397, and (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 342, and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 426.

[0163] In some embodiments, the NARE comprises (i) SEQ ID NO: 397, and (ii) SEQ ID NO: 342, and (iii) SEQ ID NO: 426.

[0164] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 393, (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 334 or 342, and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 426.

[0165] In some embodiments, the NARE comprises (i) SEQ ID NO: 393, and (ii) SEQ ID NO: 334 or 342, and (iii) SEQ ID NO: 426.

[0166] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 393, and (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 342, and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 426.

[0167] In some embodiments, the NARE comprises (i) SEQ ID NO: 393, and (ii) SEQ ID NO: 342, and (iii) SEQ ID NO: 426.

[0168] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 394, (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 334 or 342, and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 426.

[0169] In some embodiments, the NARE comprises (i) SEQ ID NO: 394, and (ii) SEQ ID NO: 334 or 342, and (iii) SEQ ID NO: 426.

[0170] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 394, and (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 342, and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 426.

[0171] In some embodiments, the NARE comprises (i) SEQ ID NO: 394, and (ii) SEQ ID NO: 342, and (iii) SEQ ID NO: 426.

[0172] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 395; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 334 or 342; and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 426.

[0173] In some embodiments, the NARE comprises (i) SEQ ID NO: 395, and (ii) SEQ ID NO: 334 or 342, and (iii) SEQ ID NO: 426.

[0174] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 395, and (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 342, and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 426.

[0175] In some embodiments, the NARE comprises (i) SEQ ID NO: 395, and (ii) SEQ ID NO: 342, and (iii) SEQ ID NO: 426.

[0176] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 384, (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 334 or 342, and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 426.

[0177] In some embodiments, the NARE comprises (i) SEQ ID NO: 384, and (ii) SEQ ID NO: 334 or 342, and (iii) SEQ ID NO: 426.

[0178] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 384, and (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 342, and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 426.

[0179] In some embodiments, the NARE comprises (i) SEQ ID NO: 384, and (ii) SEQ ID NO: 342, and (iii) SEQ ID NO: 426.

[0180] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 401; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 334 or 342; and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 426.

[0181] In some embodiments, the NARE comprises (i) SEQ ID NO: 401, and (ii) SEQ ID NO: 334 or 342, and (iii) SEQ ID NO: 426.

[0182] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 401, and (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 342, and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 426.

[0183] In some embodiments, the NARE comprises (i) SEQ ID NO: 401, and (ii) SEQ ID NO: 342, and (iii) SEQ ID NO: 426.

[0184] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 400, (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 334 or 342, and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 426.

[0185] In some embodiments, the NARE comprises (i) SEQ ID NO: 400, and (ii) SEQ ID NO: 334 or 342, and (iii) SEQ ID NO: 426.

[0186] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 400, and (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 342, and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 426.

[0187] In some embodiments, the NARE comprises (i) SEQ ID NO: 400, and (ii) SEQ ID NO: 342, and (iii) SEQ ID NO: 426.

[0188] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 381; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 334 or 342; and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 426.

[0189] In some embodiments, the NARE comprises (i) SEQ ID NO: 381, and (ii) SEQ ID NO: 334 or 342, and (iii) SEQ ID NO: 426.

[0190] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 381, and (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 342, and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 426.

[0191] In some embodiments, the NARE comprises (i) SEQ ID NO: 381, and (ii) SEQ ID NO: 342, and (iii) SEQ ID NO: 426.

[0192] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 392, (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 334 or 342, and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 426.

[0193] In some embodiments, the NARE comprises (i) SEQ ID NO: 392, and (ii) SEQ ID NO: 334 or 342, and (iii) SEQ ID NO: 426.

[0194] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 392, and (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 342, and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 426.

[0195] In some embodiments, the NARE comprises (i) SEQ ID NO: 392, and (ii) SEQ ID NO: 342, and (iii) SEQ ID NO: 426.

[0196] In some embodiments, the NARE is (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 344-349, 498; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 334 or 342; (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 302-318, 320-322, 324-327, 331, 332, or 487; % identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 333; (iv) optionally, a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 333; and (v) optionally, a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 319.

[0197] In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, 498; (ii) SEQ ID NO: 334 or 342; (iii) any one of SEQ ID NOs: 302-318, 320-322, 324-327, 331, 332, or 487; (iv) optionally, SEQ ID NO: 333; and (v) optionally, SEQ ID NO: 319.

[0198] In some embodiments, the NARE is (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 345 or 348; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 302-318, 320-322, 324-327, 331, 332, or 487; (iv) optionally, a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 333; and (v) optionally, a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 319.

[0199] In some embodiments, the NARE comprises (i) any one of SEQ ID NO: 345 or 348, (ii) SEQ ID NO: 334 or 342, (iii) any one of SEQ ID NOs: 302-318, 320-322, 324-327, 331, 332, or 487, (iv) optionally, SEQ ID NO: 333, and (v) SEQ ID NO: 319.

[0200] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 344-349, 498; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 334 or 342; and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 302-317, 320-322, 324-327, 331, 332, or 487.

[0201] In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, 498, (ii) SEQ ID NO: 334 or 342, and (iii) any one of SEQ ID NOs: 302-317, 320-322, 324-327, 331, 332, or 487.

[0202] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 345 or 348; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 334 or 442; and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 302-317, 320-322, 324-327, 331, 332, or 487.

[0203] In some embodiments, the NARE comprises (i) SEQ ID NO: 345 or 348, (ii) SEQ ID NO: 334 or 442, and (iii) any one of SEQ ID NOs: 302-317, 320-322, 324-327, 331, 332, or 487.

[0204] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 344-349, 498; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 334 or 342; and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 302-317, 320-322, 324-327, 331, 332.

[0205] In some embodiments, the NARE comprises any one of (i) SEQ ID NOs: 344-349, 498, (ii) SEQ ID NO: 334 or 342, and (iii) SEQ ID NOs: 302-317, 320-322, 324-327, 331, 332.

[0206] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 348, (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 334, and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 302-317, 320-322, 324-327, 331, and 332.

[0207] In some embodiments, the NARE comprises any one of (i) SEQ ID NO: 348, (ii) SEQ ID NO: 334, and (iii) SEQ ID NOs: 302-317, 320-322, 324-327, 331, and 332.

[0208] In some embodiments, the NARE is (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 344-349, 498; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 334 or 342; (iii) a sequence that is at least 80% identical, at least 85% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 318; (iv) sequences that are at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 333; and (v) sequences that are at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 319.

[0209] In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, 498, (ii) SEQ ID NO: 334 or 342, (iii) SEQ ID NO: 318, (iv) SEQ ID NO: 333, and (v) SEQ ID NO: 319.

[0210] In some embodiments, the NARE is (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 348; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 334; (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least (iv) sequences that are at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 333; and (v) sequences that are at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 319.

[0211] In some embodiments, the NARE comprises (i) SEQ ID NO: 348, (ii) SEQ ID NO: 334, (iii) SEQ ID NO: 318, (iv) SEQ ID NO: 333, and (v) SEQ ID NO: 319.

[0212] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 344-349, 498; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 334 or 342; and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 304.

[0213] In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, 498, (ii) SEQ ID NO: 334 or 342, and (iii) SEQ ID NO: 304.

[0214] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 348, (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 334, and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 304.

[0215] In some embodiments, the NARE comprises (i) SEQ ID NO: 348, (ii) SEQ ID NO: 334, and (iii) SEQ ID NO: 304.

[0216] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 344-349, 498; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 334 or 342; and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 305.

[0217] In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, 498, (ii) SEQ ID NO: 334 or 342, and (iii) SEQ ID NO: 305.

[0218] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 348, (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 334, and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 305.

[0219] In some embodiments, the NARE comprises (i) SEQ ID NO: 348, (ii) SEQ ID NO: 334, and (iii) SEQ ID NO: 305.

[0220] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 344-349, 498; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 334 or 342; and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 332.

[0221] In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, 498, (ii) SEQ ID NO: 334 or 342, and (iii) SEQ ID NO: 332.

[0222] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 348, (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 334, and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 332.

[0223] In some embodiments, the NARE comprises (i) SEQ ID NO: 348, (ii) SEQ ID NO: 334, and (iii) SEQ ID NO: 332.

[0224] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 344-349, 498; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 334 or 342; and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 303.

[0225] In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, 498, (ii) SEQ ID NO: 334 or 342, and (iii) SEQ ID NO: 303.

[0226] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 348, (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 334, and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 303.

[0227] In some embodiments, the NARE comprises (i) SEQ ID NO: 348, (ii) SEQ ID NO: 334, and (iii) SEQ ID NO: 303.

[0228] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 344-349, 498; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 334 or 342; and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 302.

[0229] In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, 498, (ii) SEQ ID NO: 334 or 342, and (iii) SEQ ID NO: 302.

[0230] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 348, (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 334, and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 302.

[0231] In some embodiments, the NARE comprises (i) SEQ ID NO: 348, (ii) SEQ ID NO: 334, and (iii) SEQ ID NO: 302.

[0232] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 344-349, 498; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 334 or 342; and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 306.

[0233] In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, 498, (ii) SEQ ID NO: 334 or 342, and (iii) SEQ ID NO: 306.

[0234] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 348, (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 334, and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 306.

[0235] In some embodiments, the NARE comprises (i) SEQ ID NO: 348, (ii) SEQ ID NO: 334, and (iii) SEQ ID NO: 306.

[0236] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 344-349, 498; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 334 or 342; and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 307.

[0237] In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, 498, (ii) SEQ ID NO: 334 or 342, and (iii) SEQ ID NO: 307.

[0238] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 348, (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 334, and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 307.

[0239] In some embodiments, the NARE comprises (i) SEQ ID NO: 348, (ii) SEQ ID NO: 334, and (iii) SEQ ID NO: 307.

[0240] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 344-349, 498; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 334 or 342; and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 309.

[0241] In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, 498, (ii) SEQ ID NO: 334 or 342, and (iii) SEQ ID NO: 309.

[0242] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 348, (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 334, and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 309.

[0243] In some embodiments, the NARE comprises (i) SEQ ID NO: 348, (ii) SEQ ID NO: 334, and (iii) SEQ ID NO: 309.

[0244] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 344-349, 498; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 334 or 342; and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 308.

[0245] In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, 498, (ii) SEQ ID NO: 334 or 342, and (iii) SEQ ID NO: 308.

[0246] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 348, (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 334, and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 308.

[0247] In some embodiments, the NARE comprises (i) SEQ ID NO: 348, (ii) SEQ ID NO: 334, and (iii) SEQ ID NO: 308.

[0248] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 344-349, 498; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 334 or 342; and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 310.

[0249] In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, 498, (ii) SEQ ID NO: 334 or 342, and (iii) SEQ ID NO: 310.

[0250] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 348, (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 334, and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 310.

[0251] In some embodiments, the NARE comprises (i) SEQ ID NO: 348, (ii) SEQ ID NO: 334, and (iii) SEQ ID NO: 310.

[0252] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 344-349, 498; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 334 or 342; and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 317.

[0253] In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, 498, (ii) SEQ ID NO: 334 or 342, and (iii) SEQ ID NO: 317.

[0254] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 348, (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 334, and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 317.

[0255] In some embodiments, the NARE comprises (i) SEQ ID NO: 348, (ii) SEQ ID NO: 334, and (iii) SEQ ID NO: 317.

[0256] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 344-349, 498; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 334 or 342; and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 315.

[0257] In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, 498, (ii) SEQ ID NO: 334 or 342, and (iii) SEQ ID NO: 315.

[0258] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 348, (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 334, and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 315.

[0259] In some embodiments, the NARE comprises (i) SEQ ID NO: 348, (ii) SEQ ID NO: 334, and (iii) SEQ ID NO: 315.

[0260] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 344-349, 498; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 334 or 342; and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 312.

[0261] In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, 498, (ii) SEQ ID NO: 334 or 342, and (iii) SEQ ID NO: 312.

[0262] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 348, (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 334, and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 312.

[0263] In some embodiments, the NARE comprises (i) SEQ ID NO: 348, (ii) SEQ ID NO: 334, and (iii) SEQ ID NO: 312.

[0264] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 344-349, 498; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 334 or 342; and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 316.

[0265] In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, 498, (ii) SEQ ID NO: 334 or 342, and (iii) SEQ ID NO: 316.

[0266] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 348, (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 334, and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 316.

[0267] In some embodiments, the NARE comprises (i) SEQ ID NO: 348, (ii) SEQ ID NO: 334, and (iii) SEQ ID NO: 316.

[0268] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 344-349, 498; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 334 or 342; and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 314.

[0269] In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, 498, (ii) SEQ ID NO: 334 or 342, and (iii) SEQ ID NO: 314.

[0270] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 348, (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 334, and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 314.

[0271] In some embodiments, the NARE comprises (i) SEQ ID NO: 348, (ii) SEQ ID NO: 334, and (iii) SEQ ID NO: 314.

[0272] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 344-349, 498; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 334 or 342; and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 313.

[0273] In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, 498, (ii) SEQ ID NO: 334 or 342, and (iii) SEQ ID NO: 313.

[0274] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 348, (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 334, and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 313.

[0275] In some embodiments, the NARE comprises (i) SEQ ID NO: 348, (ii) SEQ ID NO: 334, and (iii) SEQ ID NO: 313.

[0276] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 344-349, 498; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 334 or 342; and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 311.

[0277] In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, 498, (ii) SEQ ID NO: 334 or 342, and (iii) SEQ ID NO: 311.

[0278] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 348, (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 334, and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 311.

[0279] In some embodiments, the NARE comprises (i) SEQ ID NO: 348, (ii) SEQ ID NO: 334, and (iii) SEQ ID NO: 311.

[0280] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 344-349, 498; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 334 or 342; and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 321.

[0281] In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, 498, (ii) SEQ ID NO: 334 or 342, and (iii) SEQ ID NO: 321.

[0282] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 348, (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 334, and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 321.

[0283] In some embodiments, the NARE comprises (i) SEQ ID NO: 348, (ii) SEQ ID NO: 334, and (iii) SEQ ID NO: 321.

[0284] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 344-349, 498; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 334 or 342; and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 322.

[0285] In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, 498, (ii) SEQ ID NO: 334 or 342, and (iii) SEQ ID NO: 322.

[0286] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 348, (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 334, and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 322.

[0287] In some embodiments, the NARE comprises (i) SEQ ID NO: 348, (ii) SEQ ID NO: 334, and (iii) SEQ ID NO: 322.

[0288] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 344-349, 498; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 334 or 342; and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 320.

[0289] In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, 498, (ii) SEQ ID NO: 334 or 342, and (iii) SEQ ID NO: 320.

[0290] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 348, (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 334, and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 320.

[0291] In some embodiments, the NARE comprises (i) SEQ ID NO: 348, (ii) SEQ ID NO: 334, and (iii) SEQ ID NO: 320.

[0292] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 344-349, 498; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 334 or 342; and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 324.

[0293] In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, 498, (ii) SEQ ID NO: 334 or 342, and (iii) SEQ ID NO: 324.

[0294] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 348, (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 334, and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 324.

[0295] In some embodiments, the NARE comprises (i) SEQ ID NO: 348, (ii) SEQ ID NO: 334, and (iii) SEQ ID NO: 324.

[0296] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 344-349, 498; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 334 or 342; and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 331.

[0297] In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, 498, (ii) SEQ ID NO: 334 or 342, and (iii) SEQ ID NO: 331.

[0298] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 348, (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 334, and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 331.

[0299] In some embodiments, the NARE comprises (i) SEQ ID NO: 348, (ii) SEQ ID NO: 334, and (iii) SEQ ID NO: 331.

[0300] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 344-349, 498; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 334 or 342; and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 327.

[0301] In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, 498, (ii) SEQ ID NO: 334 or 342, and (iii) SEQ ID NO: 327.

[0302] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 348, (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 334, and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 327.

[0303] In some embodiments, the NARE comprises (i) SEQ ID NO: 348, (ii) SEQ ID NO: 334, and (iii) SEQ ID NO: 327.

[0304] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 344-349, 498; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 334 or 342; and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 325.

[0305] In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, 498, (ii) SEQ ID NO: 334 or 342, and (iii) SEQ ID NO: 325.

[0306] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 348, (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 334, and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 325.

[0307] In some embodiments, the NARE comprises (i) SEQ ID NO: 348, (ii) SEQ ID NO: 334, and (iii) SEQ ID NO: 325.

[0308] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 344-349, 498; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 334 or 342; and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 326.

[0309] In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, 498, (ii) SEQ ID NO: 334 or 342, and (iii) SEQ ID NO: 326.

[0310] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 348, (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 334, and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 326.

[0311] In some embodiments, the NARE comprises (i) SEQ ID NO: 348, (ii) SEQ ID NO: 334, and (iii) SEQ ID NO: 326.

[0312] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 344-349, 498; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 334 or 342; and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 487.

[0313] In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, 498, (ii) SEQ ID NO: 334 or 342, and (iii) SEQ ID NO: 487.

[0314] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 345, (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 342, and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 487.

[0315] In some embodiments, the NARE comprises (i) SEQ ID NO: 345, (ii) SEQ ID NO: 342, and (iii) SEQ ID NO: 487.

[0316] In some embodiments, the NARE is (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 344-349, 498; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 351-356, 499, 500; or (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, or at least 97% identical to any one of SEQ ID NOs: 200, 370, 417-420, 502, 441, 482-485, 489, 491-496. and (iv) optionally, a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 444, 452, 488; (v) optionally, a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 402; and (vi) optionally, a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 433.

[0317] In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, 498, (ii) any one of SEQ ID NOs: 351-356, 499, 500, (iii) any one of SEQ ID NOs: 200, 370, 417-420, 502, 441, 482-485, 489, 491-496, and (iv) optionally, any one of SEQ ID NOs: 444, 452, or 488, (v) optionally, SEQ ID NO: 402, and (vi) optionally, SEQ ID NO: 433.

[0318] In some embodiments, the NARE is (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 344-349, 498; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 351-356, 499, 500; (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 351-356, 499, 500; ) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 200, 370, 417-420, 502, 482-485, 489, 491-496, and (iv) optionally, a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 444 or 452.

[0319] In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, 498; (ii) any one of SEQ ID NOs: 351-356, 499, 500; (iii) any one of SEQ ID NOs: 200, 370, 417-420, 502, 482-485, 489, 491-496; and (iv) optionally, SEQ ID NO: 444 or 452.

[0320] In some embodiments, the NARE is (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 344-349, 498; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 351-356, 499, 500; (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 200, 370, 417, 482-485, 489, 491-496, and (iv) optionally, a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 444 or 452.

[0321] In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, 498; (ii) any one of SEQ ID NOs: 351-356, 499, 500; (iii) any one of SEQ ID NOs: 200, 370, 417, 482-485, 489, 491-496; and (iv) optionally, SEQ ID NO: 444 or 452.

[0322] In some embodiments, the NARE is (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 344-349, 498; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 351-356, 499, 500. (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 200, 417-420, 502, 485; and (iv) optionally, a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 444 or 452.

[0323] In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, 498; (ii) any one of SEQ ID NOs: 351-356, 499, 500; (iii) any one of SEQ ID NOs: 200, 417-420, 502, 485; and (iv) optionally, SEQ ID NO: 444 or 452.

[0324] In some embodiments, the NARE is (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 344-349, 498; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 351-356, 499, 500; % identical to any one of SEQ ID NOs: 200, 417, or 485; (iii) sequences that are at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 200, 417, or 485; and (iv) optionally, sequences that are at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 444 or 452.

[0325] In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, 498, (ii) any one of SEQ ID NOs: 351-356, 499, 500, (iii) any one of SEQ ID NOs: 200, 417, or 485, and (iv) optionally, SEQ ID NO: 444 or 452.

[0326] In some embodiments, the NARE comprises: (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 344-349, 498; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 351-356, 499, 500; and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 370, 482-484, 489, 491-496.

[0327] In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, 498, (ii) any one of SEQ ID NOs: 351-356, 499, 500, and (iii) any one of SEQ ID NOs: 370, 482-484, 489, 491-496.

[0328] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 349, (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 353, and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 370, 482-484, 489, 491-496.

[0329] In some embodiments, the NARE comprises any one of (i) SEQ ID NO: 349, (ii) SEQ ID NO: 353, and (iii) SEQ ID NOs: 370, 482-484, 489, 491-496.

[0330] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 344-349, 498; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 355; and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 200.

[0331] In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, 498, (ii) SEQ ID NO: 355, and (iii) SEQ ID NO: 200.

[0332] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 349, (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 355, and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 200.

[0333] In some embodiments, the NARE comprises (i) SEQ ID NO: 349, (ii) SEQ ID NO: 355, and (iii) SEQ ID NO: 200.

[0334] In some embodiments, the NARE is (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 344-349, 498; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical to any one of SEQ ID NOs: 351-356, 499, 500; (iii) sequences that are at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 417-420, 502; and (iv) sequences that are at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 452.

[0335] In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, 498, (ii) any one of SEQ ID NOs: 351-356, 499, 500, (iii) any one of SEQ ID NOs: 417-420, 502, and (iv) SEQ ID NO: 452.

[0336] In some embodiments, the NARE comprises: (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 346; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 500; (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 417; and (iv) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 452.

[0337] In some embodiments, the NARE comprises (i) SEQ ID NO: 346, (ii) SEQ ID NO: 500, (iii) SEQ ID NO: 417, and (iv) SEQ ID NO: 452.

[0338] In some embodiments, the NARE is (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 344-349, 498; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical to any one of SEQ ID NOs: 351-356, 499, 500; (iii) sequences that are at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 417-420, 502; and (iv) sequences that are at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 444.

[0339] In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, 498, (ii) any one of SEQ ID NOs: 351-356, 499, 500, (iii) any one of SEQ ID NOs: 417-420, 502, and (iv) SEQ ID NO: 452.

[0340] In some embodiments, the NARE comprises: (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 349; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 354; (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 502; and (iv) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 444.

[0341] In some embodiments, the NARE comprises (i) SEQ ID NO: 349, (ii) SEQ ID NO: 354, (iii) SEQ ID NO: 502, and (iv) SEQ ID NO: 444.

[0342] In some embodiments, the NARE is (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 344-349, 498; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 351-356, 499, 500; (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 99% identical to SEQ ID NO: 441. (iv) sequences that are at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 488; (v) sequences that are at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 402; and (vi) sequences that are at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 433.

[0343] In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, 498, (ii) any one of SEQ ID NOs: 351-356, 499, 500, (iii) SEQ ID NO: 441, (iv) SEQ ID NO: 488, (v) SEQ ID NO: 402, and (vi) SEQ ID NO: 433.

[0344] In some embodiments, the NARE is (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 347; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 351; (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 441. (iv) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 488; (v) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 402; and (vi) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 433.

[0345] In some embodiments, the NARE comprises (i) SEQ ID NO: 347, (ii) SEQ ID NO: 351, (iii) SEQ ID NO: 441, (iv) SEQ ID NO: 488, (v) SEQ ID NO: 402, and (vi) SEQ ID NO: 433.

[0346] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 344-349, 498; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 351-356, 499, 500; and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 489.

[0347] In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, 498, (ii) any one of SEQ ID NOs: 351-356, 499, 500, and (iii) SEQ ID NO: 489.

[0348] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 349, (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 353, and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 489.

[0349] In some embodiments, the NARE comprises (i) SEQ ID NO: 349, (ii) SEQ ID NO: 353, and (iii) SEQ ID NO: 489.

[0350] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 344-349, 498; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 351-356, 499, 500; and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 370.

[0351] In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, 498, (ii) any one of SEQ ID NOs: 351-356, 499, 500, and (iii) SEQ ID NO: 370.

[0352] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 349, (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 353, and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 370.

[0353] In some embodiments, the NARE comprises (i) SEQ ID NO: 349, (ii) SEQ ID NO: 353, and (iii) SEQ ID NO: 370.

[0354] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 344-349, 498; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 351-356, 499, 500; and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 483.

[0355] In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, 498, (ii) any one of SEQ ID NOs: 351-356, 499, 500, and (iii) SEQ ID NO: 483.

[0356] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 349, (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 353, and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 483.

[0357] In some embodiments, the NARE comprises (i) SEQ ID NO: 349, (ii) SEQ ID NO: 353, and (iii) SEQ ID NO: 483.

[0358] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 344-349, 498; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 351-356, 499, 500; and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 484.

[0359] In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, 498, (ii) any one of SEQ ID NOs: 351-356, 499, 500, and (iii) SEQ ID NO: 484.

[0360] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 349, (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 353, and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 484.

[0361] In some embodiments, the NARE comprises (i) SEQ ID NO: 349, (ii) SEQ ID NO: 353, and (iii) SEQ ID NO: 484.

[0362] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 344-349, 498; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 351-356, 499, 500; and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 482.

[0363] In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, 498, (ii) any one of SEQ ID NOs: 351-356, 499, 500, and (iii) SEQ ID NO: 482.

[0364] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 349, (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 353, and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 482.

[0365] In some embodiments, the NARE comprises (i) SEQ ID NO: 349, (ii) SEQ ID NO: 353, and (iii) SEQ ID NO: 482.

[0366] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 344-349, 498; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 351-356, 499, 500; and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 491.

[0367] In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, 498, (ii) any one of SEQ ID NOs: 351-356, 499, 500, and (iii) SEQ ID NO: 491.

[0368] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 349, (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 353, and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 491.

[0369] In some embodiments, the NARE comprises (i) SEQ ID NO: 349, (ii) SEQ ID NO: 353, and (iii) SEQ ID NO: 491.

[0370] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 344-349, 498; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 351-356, 499, 500; and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 492.

[0371] In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, 498, (ii) any one of SEQ ID NOs: 351-356, 499, 500, and (iii) SEQ ID NO: 492.

[0372] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 349, (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 353, and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 492.

[0373] In some embodiments, the NARE comprises (i) SEQ ID NO: 349, (ii) SEQ ID NO: 353, and (iii) SEQ ID NO: 492.

[0374] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 344-349, 498; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 351-356, 499, 500; and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 495.

[0375] In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, 498, (ii) any one of SEQ ID NOs: 351-356, 499, 500, and (iii) SEQ ID NO: 495.

[0376] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 349, (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 353, and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 495.

[0377] In some embodiments, the NARE comprises (i) SEQ ID NO: 349, (ii) SEQ ID NO: 353, and (iii) SEQ ID NO: 495.

[0378] In some embodiments, the NARE comprises: (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 344-349, 498; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 351-356, 499, 500; and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 493.

[0379] In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, 498, (ii) any one of SEQ ID NOs: 351-356, 499, 500, and (iii) SEQ ID NO: 493.

[0380] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 349, (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 499, and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 493.

[0381] In some embodiments, the NARE comprises (i) SEQ ID NO: 349, (ii) SEQ ID NO: 499, and (iii) SEQ ID NO: 493.

[0382] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 344-349, 498; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 351-356, 499, 500; and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 494.

[0383] In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, 498, (ii) any one of SEQ ID NOs: 351-356, 499, 500, and (iii) SEQ ID NO: 494.

[0384] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 349, (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 353, and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 494.

[0385] In some embodiments, the NARE comprises (i) SEQ ID NO: 349, (ii) SEQ ID NO: 353, and (iii) SEQ ID NO: 494.

[0386] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 344-349, 498; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 351-356, 499, 500; and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 496.

[0387] In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, 498, (ii) any one of SEQ ID NOs: 351-356, 499, 500, and (iii) SEQ ID NO: 496.

[0388] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 349, (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 353, and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 496.

[0389] In some embodiments, the NARE comprises (i) SEQ ID NO: 349, (ii) SEQ ID NO: 353, and (iii) SEQ ID NO: 496.

[0390] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 344-349, 498; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 351-356, 499, 500; and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 485.

[0391] In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, 498, (ii) any one of SEQ ID NOs: 351-356, 499, 500, and (iii) SEQ ID NO: 485.

[0392] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 349, (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 352, and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 485.

[0393] In some embodiments, the NARE comprises (i) SEQ ID NO: 349, (ii) SEQ ID NO: 352, and (iii) SEQ ID NO: 485.

[0394] In some embodiments, the NARE is (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 344-349, 498; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 335; (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 294, 295, 296, 297, 298, 300, 301, 302, 303, 304, 305, 306, 307, 308, 309, 310, 311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322, 323, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335, 336, 337, 338, 339, 340, 341, 342, 343, 344 99, 323, 328, 329, 330, 407, 501, 430, 431, 503, 434, 504, and (iv) optionally, a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NO: 444.

[0395] In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, 498, (ii) SEQ ID NO: 335, and (iii) any one of SEQ ID NOs: 294, 295, 296, 299, 323, 328, 329, 330, 407, 501, 430, 431, 503, 434, 504, and (iv) optionally SEQ ID NO: 444.

[0396] In some embodiments, the NARE is selected from the group consisting of: (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 348; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 335; and (iii) a sequence selected from the group consisting of SEQ ID NOs: 294, 296, 299. , 323, 328, 329, 330, 407, 430, 434, and (iv) optionally, a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NO: 444.

[0397] In some embodiments, the NARE comprises (i) SEQ ID NO: 348, (ii) SEQ ID NO: 335, and (iii) any one of SEQ ID NOs: 294, 296, 299, 323, 328, 329, 330, 407, 430, 434, and (iv) optionally, SEQ ID NO: 444.

[0398] In some embodiments, the NARE is (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 344-349, 498; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 335; (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 335; Nos. 294, 295, 296, 407, 501, 430, 431, 503, 434, 504, and (iv) sequences that are at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 444.

[0399] In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, 498, (ii) SEQ ID NO: 335, and (iii) any one of SEQ ID NOs: 294, 295, 296, 407, 501, 430, 431, 503, 434, 504, and (iv) SEQ ID NO: 444.

[0400] In some embodiments, the NARE is (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 348; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 335; and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 335. (iv) sequences that are at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of sequence numbers 294, 296, 407, 430, 434, and (iv) sequences that are at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 444.

[0401] In some embodiments, the NARE comprises (i) SEQ ID NO: 348, (ii) SEQ ID NO: 335, and (iii) any one of SEQ ID NOs: 294, 296, 407, 430, 434, and (iv) SEQ ID NO: 444.

[0402] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 344-349, 498; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 335; and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 323.

[0403] In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, 498, (ii) SEQ ID NO: 335, and (iii) SEQ ID NO: 323.

[0404] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 348, (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 335, and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 323.

[0405] In some embodiments, the NARE comprises (i) SEQ ID NO: 348, (ii) SEQ ID NO: 335, and (iii) SEQ ID NO: 323.

[0406] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 344-349, 498; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 335; and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 328.

[0407] In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, 498, (ii) SEQ ID NO: 335, and (iii) SEQ ID NO: 328.

[0408] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 348, (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 335, and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 328.

[0409] In some embodiments, the NARE comprises (i) SEQ ID NO: 348, (ii) SEQ ID NO: 335, and (iii) SEQ ID NO: 328.

[0410] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 344-349, 498; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 335; and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 330.

[0411] In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, 498, (ii) SEQ ID NO: 335, and (iii) SEQ ID NO: 330.

[0412] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 348, (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 335, and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 330.

[0413] In some embodiments, the NARE comprises (i) SEQ ID NO: 348, (ii) SEQ ID NO: 335, and (iii) SEQ ID NO: 330.

[0414] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 344-349, 498; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 335; and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 329.

[0415] In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, 498, (ii) SEQ ID NO: 335, and (iii) SEQ ID NO: 329.

[0416] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 348, (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 335, and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 329.

[0417] In some embodiments, the NARE comprises (i) SEQ ID NO: 348, (ii) SEQ ID NO: 335, and (iii) SEQ ID NO: 329.

[0418] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 344-349, 498; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 335; and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 299.

[0419] In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, 498, (ii) SEQ ID NO: 335, and (iii) SEQ ID NO: 299.

[0420] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 348, (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 335, and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 299.

[0421] In some embodiments, the NARE comprises (i) SEQ ID NO: 348, (ii) SEQ ID NO: 335, and (iii) SEQ ID NO: 299.

[0422] In some embodiments, the NARE is (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 344-349, 498; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 335. (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 430, 431, 503; and (vi) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 444.

[0423] In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, 498, (ii) SEQ ID NO: 335, (iii) any one of SEQ ID NOs: 430, 431, 503, and (vi) SEQ ID NO: 444.

[0424] In some embodiments, the NARE comprises: (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 348; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 335; (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 503; and (vi) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 444.

[0425] In some embodiments, the NARE comprises (i) SEQ ID NO: 348, (ii) SEQ ID NO: 335, (iii) SEQ ID NO: 503, and (vi) SEQ ID NO: 444.

[0426] In some embodiments, the NARE is (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 344-349, 498; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 335. (iii) sequences that are at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 294 or 295; and (vi) sequences that are at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 444.

[0427] In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, 498, (ii) SEQ ID NO: 335, (iii) SEQ ID NO: 294 or 295, and (vi) SEQ ID NO: 444.

[0428] In some embodiments, the NARE comprises: (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 348; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 335; (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 294; and (vi) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 444.

[0429] In some embodiments, the NARE comprises (i) SEQ ID NO: 348, (ii) SEQ ID NO: 335, (iii) SEQ ID NO: 294, and (vi) SEQ ID NO: 444.

[0430] In some embodiments, the NARE is (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 344-349, 498; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 335. (iii) sequences that are at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 407 or 501; and (vi) sequences that are at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 444.

[0431] In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, 498, (ii) SEQ ID NO: 335, (iii) SEQ ID NO: 407 or 501, and (vi) SEQ ID NO: 444.

[0432] In some embodiments, the NARE comprises: (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 348; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 335; (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 501; and (vi) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 444.

[0433] In some embodiments, the NARE comprises (i) SEQ ID NO: 348, (ii) SEQ ID NO: 335, (iii) SEQ ID NO: 501, and (vi) SEQ ID NO: 444.

[0434] In some embodiments, the NARE is (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 344-349, 498; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 335. (iii) sequences that are at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 434 or 504; and (vi) sequences that are at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 444.

[0435] In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, 498, (ii) SEQ ID NO: 335, (iii) SEQ ID NO: 434 or 504, and (vi) SEQ ID NO: 444.

[0436] In some embodiments, the NARE comprises: (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 348; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 335; (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 504; and (vi) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 444.

[0437] In some embodiments, the NARE comprises (i) SEQ ID NO: 348, (ii) SEQ ID NO: 335, (iii) SEQ ID NO: 504, and (vi) SEQ ID NO: 444.

[0438] In some embodiments, the NARE is (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 344-349, 498; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 335; (iii) sequences that are at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 296; and (vi) sequences that are at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 444.

[0439] In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, 498, (ii) SEQ ID NO: 335, (iii) SEQ ID NO: 296, and (vi) SEQ ID NO: 444.

[0440] In some embodiments, the NARE comprises: (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 348; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 335; (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 296; and (vi) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 444.

[0441] In some embodiments, the NARE comprises (i) SEQ ID NO: 348, (ii) SEQ ID NO: 335, (iii) SEQ ID NO: 296, and (vi) SEQ ID NO: 444.

[0442] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 339, 363-369, 378, 379, 382, ​​385, 387-389, 391, 398, 399, and (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 430, 431, 503.

[0443] In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 339, 363-369, 378, 379, 382, ​​385, 387-389, 391, 398, 399, and (ii) any one of SEQ ID NOs: 430, 431, 503.

[0444] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 339, 363-369, 378, 379, 382, ​​385, 387-389, 391, 398, 399, and (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 430.

[0445] In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 339, 363-369, 378, 379, 382, ​​385, 387-389, 391, 398, 399, and (ii) SEQ ID NO: 430.

[0446] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 369, and (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 430, 431, 503.

[0447] In some embodiments, the NARE comprises (i) SEQ ID NO: 369, and (ii) any one of SEQ ID NOs: 430, 431, 503.

[0448] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 369, and (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 430.

[0449] In some embodiments, the NARE comprises (i) SEQ ID NO: 369, and (ii) SEQ ID NO: 430.

[0450] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 364, and (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 430, 431, 503.

[0451] In some embodiments, the NARE comprises (i) SEQ ID NO: 364, and (ii) any one of SEQ ID NOs: 430, 431, 503.

[0452] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 364, and (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 430.

[0453] In some embodiments, the NARE comprises (i) SEQ ID NO: 364, and (ii) SEQ ID NO: 430.

[0454] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 365, and (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 430, 431, 503.

[0455] In some embodiments, the NARE comprises (i) SEQ ID NO: 365, and (ii) any one of SEQ ID NOs: 430, 431, 503.

[0456] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 365, and (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 430.

[0457] In some embodiments, the NARE comprises (i) SEQ ID NO: 365, and (ii) SEQ ID NO: 430.

[0458] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 366, and (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 430, 431, 503.

[0459] In some embodiments, the NARE comprises (i) SEQ ID NO: 366, and (ii) any one of SEQ ID NOs: 430, 431, 503.

[0460] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 366, and (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 430.

[0461] In some embodiments, the NARE comprises (i) SEQ ID NO: 366, and (ii) SEQ ID NO: 430.

[0462] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 367, and (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 430, 431, 503.

[0463] In some embodiments, the NARE comprises (i) SEQ ID NO: 367, and (ii) any one of SEQ ID NOs: 430, 431, 503.

[0464] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 367, and (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 430.

[0465] In some embodiments, the NARE comprises (i) SEQ ID NO: 367, and (ii) SEQ ID NO: 430.

[0466] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 368, and (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 430, 431, 503.

[0467] In some embodiments, the NARE comprises (i) SEQ ID NO: 368, and (ii) any one of SEQ ID NOs: 430, 431, 503.

[0468] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 368, and (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 430.

[0469] In some embodiments, the NARE comprises (i) SEQ ID NO: 368, and (ii) SEQ ID NO: 430.

[0470] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 363, and (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 430, 431, 503.

[0471] In some embodiments, the NARE comprises (i) SEQ ID NO: 363, and (ii) any one of SEQ ID NOs: 430, 431, 503.

[0472] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 363, and (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 430.

[0473] In some embodiments, the NARE comprises (i) SEQ ID NO: 363, and (ii) SEQ ID NO: 430.

[0474] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 378, and (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 430, 431, 503.

[0475] In some embodiments, the NARE comprises (i) SEQ ID NO: 378, and (ii) any one of SEQ ID NOs: 430, 431, 503.

[0476] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 378, and (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 430.

[0477] In some embodiments, the NARE comprises (i) SEQ ID NO: 378, and (ii) SEQ ID NO: 430.

[0478] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 379, and (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 430, 431, 503.

[0479] In some embodiments, the NARE comprises (i) SEQ ID NO: 379, and (ii) any one of SEQ ID NOs: 430, 431, 503.

[0480] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 379, and (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 430.

[0481] In some embodiments, the NARE comprises (i) SEQ ID NO: 379, and (ii) SEQ ID NO: 430.

[0482] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 382, ​​and (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 430, 431, 503.

[0483] In some embodiments, the NARE comprises (i) SEQ ID NO: 382, ​​and (ii) any one of SEQ ID NOs: 430, 431, 503.

[0484] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 382, ​​and (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 430.

[0485] In some embodiments, the NARE comprises (i) SEQ ID NO: 382, ​​and (ii) SEQ ID NO: 430.

[0486] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 385, and (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 430, 431, 503.

[0487] In some embodiments, the NARE comprises (i) SEQ ID NO: 385, and (ii) any one of SEQ ID NOs: 430, 431, 503.

[0488] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 385, and (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 430.

[0489] In some embodiments, the NARE comprises (i) SEQ ID NO: 385, and (ii) SEQ ID NO: 430.

[0490] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 387, and (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 430, 431, 503.

[0491] In some embodiments, the NARE comprises (i) SEQ ID NO: 387, and (ii) any one of SEQ ID NOs: 430, 431, 503.

[0492] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 387, and (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 430.

[0493] In some embodiments, the NARE comprises (i) SEQ ID NO: 387, and (ii) SEQ ID NO: 430.

[0494] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 388, and (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 430, 431, 503.

[0495] In some embodiments, the NARE comprises (i) SEQ ID NO: 388, and (ii) any one of SEQ ID NOs: 430, 431, 503.

[0496] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 388, and (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 430.

[0497] In some embodiments, the NARE comprises (i) SEQ ID NO: 388, and (ii) SEQ ID NO: 430.

[0498] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 389, and (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 430, 431, 503.

[0499] In some embodiments, the NARE comprises (i) SEQ ID NO: 389, and (ii) any one of SEQ ID NOs: 430, 431, 503.

[0500] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 389, and (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 430.

[0501] In some embodiments, the NARE comprises (i) SEQ ID NO: 389, and (ii) SEQ ID NO: 430.

[0502] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 391, and (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 430, 431, 503.

[0503] In some embodiments, the NARE comprises (i) SEQ ID NO: 391, and (ii) any one of SEQ ID NOs: 430, 431, 503.

[0504] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 391, and (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 430.

[0505] In some embodiments, the NARE comprises (i) SEQ ID NO: 391, and (ii) SEQ ID NO: 430.

[0506] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 398, and (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 430, 431, 503.

[0507] In some embodiments, the NARE comprises (i) SEQ ID NO: 398, and (ii) any one of SEQ ID NOs: 430, 431, 503.

[0508] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 398, and (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 430.

[0509] In some embodiments, the NARE comprises (i) SEQ ID NO: 398, and (ii) SEQ ID NO: 430.

[0510] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 399, and (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 430, 431, 503.

[0511] In some embodiments, the NARE comprises (i) SEQ ID NO: 399, and (ii) any one of SEQ ID NOs: 430, 431, 503.

[0512] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 399, and (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 430.

[0513] In some embodiments, the NARE comprises (i) SEQ ID NO: 399, and (ii) SEQ ID NO: 430.

[0514] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 339, and (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 430, 431, 503.

[0515] In some embodiments, the NARE comprises (i) SEQ ID NO: 339, and (ii) any one of SEQ ID NOs: 430, 431, 503.

[0516] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 339, and (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 430.

[0517] In some embodiments, the NARE comprises (i) SEQ ID NO: 339, and (ii) SEQ ID NO: 430.

[0518] In some embodiments, the NARE comprises a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 138-161.

[0519] In some embodiments, the NARE comprises any one of SEQ ID NOs: 138-161.

[0520] In some embodiments, the NARE comprises (i) a sequence that is optionally at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 475; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 298; and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 444.

[0521] In some embodiments, the NARE comprises (i) optionally SEQ ID NO: 475, (ii) SEQ ID NO: 298, and (iii) SEQ ID NO: 444.

[0522] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 298, and (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 444.

[0523] In some embodiments, the NARE comprises (i) SEQ ID NO: 298, and (ii) SEQ ID NO: 444.

[0524] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 475, (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 298, and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 444.

[0525] In some embodiments, the NARE comprises (i) SEQ ID NO: 475, (ii) SEQ ID NO: 298, and (iii) SEQ ID NO: 444.

[0526] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 339, 380, 383, 386, 390; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 439 or 497; and (iii) optionally, a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 444.

[0527] In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 339, 380, 383, 386, 390; (ii) SEQ ID NO: 439 or 497; and (iii) optionally, SEQ ID NO: 444.

[0528] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 339, 380, 383, 386, 390, and (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 439 or 497.

[0529] In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 339, 380, 383, 386, 390, and (ii) SEQ ID NO: 439 or 497.

[0530] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 339, and (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 439 or 497.

[0531] In some embodiments, the NARE comprises (i) SEQ ID NO: 339, and (ii) SEQ ID NO: 439 or 497.

[0532] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 339, and (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 439.

[0533] In some embodiments, the NARE comprises (i) SEQ ID NO: 339, and (ii) SEQ ID NO: 439.

[0534] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 380, and (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to c.

[0535] In some embodiments, the NARE comprises (i) SEQ ID NO: 380, and (ii) SEQ ID NO: 439 or 497.

[0536] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 380, and (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 439.

[0537] In some embodiments, the NARE comprises (i) SEQ ID NO: 380, and (ii) SEQ ID NO: 439.

[0538] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 383, and (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 439 or 497.

[0539] In some embodiments, the NARE comprises (i) SEQ ID NO: 383, and (ii) SEQ ID NO: 439 or 497.

[0540] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 383, and (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 439.

[0541] In some embodiments, the NARE comprises (i) SEQ ID NO: 383, and (ii) SEQ ID NO: 439.

[0542] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 386, and (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 439 or 497.

[0543] In some embodiments, the NARE comprises (i) SEQ ID NO: 386, and (ii) SEQ ID NO: 439 or 497.

[0544] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 386, and (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 439.

[0545] In some embodiments, the NARE comprises (i) SEQ ID NO: 386, and (ii) SEQ ID NO: 439.

[0546] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 390, and (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 439 or 497.

[0547] In some embodiments, the NARE comprises (i) SEQ ID NO: 390, and (ii) SEQ ID NO: 439 or 497.

[0548] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 390, and (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 497.

[0549] In some embodiments, the NARE comprises (i) SEQ ID NO: 390, and (ii) SEQ ID NO: 497.

[0550] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 390, and (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 439.

[0551] In some embodiments, the NARE comprises (i) SEQ ID NO: 390, and (ii) SEQ ID NO: 439.

[0552] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 390, (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 439 or 497, and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 444.

[0553] In some embodiments, the NARE comprises (i) SEQ ID NO: 390, (ii) SEQ ID NO: 439 or 497, and (iii) SEQ ID NO: 444.

[0554] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 390, (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 439, and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 444.

[0555] In some embodiments, the NARE comprises (i) SEQ ID NO: 390, (ii) SEQ ID NO: 439, and (iii) SEQ ID NO: 444.

[0556] In some embodiments, the NARE is (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 344-349, 498; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical to SEQ ID NO: 336; and (iii) sequences that are at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 201, 284, 285, 301, 362, 372, 373, 403-406, 408-410, 412, 427, 444, 453-456, 486, and 490.

[0557] In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, 498, (ii) SEQ ID NO: 336, and (iii) any one of SEQ ID NOs: 201, 284, 285, 301, 362, 372, 373, 403-406, 408-410, 412, 427, 444, 453-456, 486, 490.

[0558] In some embodiments, the NARE is (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 348; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, or at least 98% identical to SEQ ID NO: 336; and (iii) sequences that are at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 201, 284, 285, 301, 362, 372, 373, 403-406, 408-410, 412, 427, 444, 453-456, 486, and 490.

[0559] In some embodiments, the NARE comprises any one of (i) SEQ ID NO: 348, (ii) SEQ ID NO: 336, and (iii) SEQ ID NOs: 201, 284, 285, 301, 362, 372, 373, 403-406, 408-410, 412, 427, 444, 453-456, 486, and 490.

[0560] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 344-349, 498; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 336; and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 444.

[0561] In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, 498, (ii) SEQ ID NO: 336, and (iii) SEQ ID NO: 444.

[0562] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 348, (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 336, and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 444.

[0563] In some embodiments, the NARE comprises (i) SEQ ID NO: 348, (ii) SEQ ID NO: 336, and (iii) SEQ ID NO: 444.

[0564] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 344-349, 498; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 336; and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 372.

[0565] In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, 498, (ii) SEQ ID NO: 336, and (iii) SEQ ID NO: 372.

[0566] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 348, (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 336, and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 372.

[0567] In some embodiments, the NARE comprises (i) SEQ ID NO: 348, (ii) SEQ ID NO: 336, and (iii) SEQ ID NO: 372.

[0568] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 344-349, 498; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 336; and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 373.

[0569] In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, 498, (ii) SEQ ID NO: 336, and (iii) SEQ ID NO: 373.

[0570] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 348, (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 336, and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 373.

[0571] In some embodiments, the NARE comprises (i) SEQ ID NO: 348, (ii) SEQ ID NO: 336, and (iii) SEQ ID NO: 373.

[0572] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 344-349, 498; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 336; and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 486.

[0573] In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, 498, (ii) SEQ ID NO: 336, and (iii) SEQ ID NO: 486.

[0574] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 348, (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 336, and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 486.

[0575] In some embodiments, the NARE comprises (i) SEQ ID NO: 348, (ii) SEQ ID NO: 336, and (iii) SEQ ID NO: 486.

[0576] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 344-349, 498; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 336; and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 456.

[0577] In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, 498, (ii) SEQ ID NO: 336, and (iii) SEQ ID NO: 456.

[0578] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 348, (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 336, and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 456.

[0579] In some embodiments, the NARE comprises (i) SEQ ID NO: 348, (ii) SEQ ID NO: 336, and (iii) SEQ ID NO: 456.

[0580] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 344-349, 498; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 336; and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 455.

[0581] In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, 498, (ii) SEQ ID NO: 336, and (iii) SEQ ID NO: 455.

[0582] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 348, (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 336, and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 455.

[0583] In some embodiments, the NARE comprises (i) SEQ ID NO: 348, (ii) SEQ ID NO: 336, and (iii) SEQ ID NO: 455.

[0584] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 344-349, 498; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 336; and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 406.

[0585] In some embodiments, the NARE comprises (i) any one of SEQ ID NOs: 344-349, 498, (ii) SEQ ID NO: 336, and (iii) SEQ ID NO: 406.

[0586] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 348, (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 336, and (iii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO: 406.

[0587] In some embodiments, the NARE comprises (i) SEQ ID NO: 348, (ii) SEQ ID NO: 336, and (iii) SEQ ID NO: 406.

[0588] In some embodiments, the NARE comprises (i) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to any one of SEQ ID NOs: 344-349, 498; (ii) a sequence that is at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, or at least 99% identical to SEQ ID NO...

Claims

1. (i) a sequence that is at least 90% identical to any one of SEQ ID NOs: 344-349, 498; (ii) a sequence that is at least 90% identical to any one of SEQ ID NOs: 337, 338, 355, 357, 358, 359, 407, 411, 429-431, 434, 501, 503, or 504; (iii) optionally, a sequence that is at least 90% identical to any one of SEQ ID NOs: 323, 420, or 488; and (iv) optionally, a sequence that is at least 90% identical to SEQ ID NO: 402 or 444.

2. 2. The NARE of claim 1, comprising: (i) a sequence that is at least 95% identical to any one of SEQ ID NOs: 344-349, or 498; (ii) a sequence that is at least 95% identical to any one of SEQ ID NOs: 337, 338, 355, 357, 358, 359, 407, 411, 429-431, 434, 501, 503, or 504; (iii) optionally, a sequence that is at least 95% identical to any one of SEQ ID NOs: 323, 420, 488; and (iv) optionally, a sequence that is at least 95% identical to SEQ ID NO: 402 or 444.

3. 2. The NARE of claim 1, comprising: (i) any one of SEQ ID NOs: 344-349, or 498; (ii) any one of SEQ ID NOs: 337, 338, 355, 357, 358, 359, 407, 411, 429-431, 434, 501, 503, or 504; (iii) optionally, any one of SEQ ID NOs: 323, 420, 488; and (iv) optionally, SEQ ID NO: 402 or 444.

4. A NARE comprising: (i) a sequence that is at least 90% identical to any one of SEQ ID NOs: 381, 384, 392, 393, 394, 395, 396, 397, 400, or 401; (ii) a sequence that is at least 90% identical to SEQ ID NO: 334 or SEQ ID NO: 342; and (iii) a sequence that is at least 90% identical to SEQ ID NO:

426.

5. 5. The NARE of claim 4, comprising: (i) a sequence that is at least 95% identical to any one of SEQ ID NOs: 381, 384, 392, 393, 394, 395, 396, 397, 400, or 401; (ii) a sequence that is at least 95% identical to SEQ ID NO: 334 or SEQ ID NO: 342; and (iii) a sequence that is at least 95% identical to SEQ ID NO:

426.

6. (i) any one of SEQ ID NOs: 381, 384, 392, 393, 394, 395, 396, 397, 400, or 401, and (ii) SEQ ID NO: 334 or SEQ ID NO: 342, and (iii) SEQ ID NO:

426.

7. (i) a sequence that is at least 90% identical to any one of SEQ ID NOs: 344-349, or 498; (ii) a sequence that is at least 90% identical to SEQ ID NO: 334 or SEQ ID NO: 342; (iii) a sequence that is at least 90% identical to any one of SEQ ID NOs: 302-318, 320-322, 324-327, 331, 332, or 487; (iv) optionally, SEQ ID NO: 333; and (v) optionally, a sequence that is at least 90% identical to SEQ ID NO:

319.

8. 8. The NARE of claim 7, comprising: (i) a sequence that is at least 95% identical to any one of SEQ ID NOs: 344-349, or 498; (ii) a sequence that is at least 95% identical to SEQ ID NO: 334 or SEQ ID NO: 342; (iii) a sequence that is at least 95% identical to any one of SEQ ID NOs: 302-318, 320-322, 324-327, 331, 332, or 487; (iv) optionally, SEQ ID NO: 333; and (v) optionally, a sequence that is at least 95% identical to SEQ ID NO:

319.

9. 8. The NARE of claim 7, comprising: (i) any one of SEQ ID NOs: 344-349, or 498; (ii) SEQ ID NO: 334 or SEQ ID NO: 342; (iii) any one of SEQ ID NOs: 302-318, 320-322, 324-327, 331, 332, or 487; (iv) optionally, SEQ ID NO: 333; and (v) optionally, SEQ ID NO:

319.

10. 8. The NARE of claim 7, comprising: (i) a sequence that is at least 90% identical to any one of SEQ ID NOs: 344-349, or 498; (ii) a sequence that is at least 90% identical to SEQ ID NO: 334 or SEQ ID NO: 342; and (iii) a sequence that is at least 90% identical to any one of SEQ ID NOs: 302-317, 320-322, 324-327, 331, 332, or 487.

11. 8. The NARE of claim 7, comprising: (i) a sequence that is at least 95% identical to any one of SEQ ID NOs: 344-349, or 498; (ii) a sequence that is at least 95% identical to SEQ ID NO: 334 or SEQ ID NO: 342; and (iii) a sequence that is at least 95% identical to any one of SEQ ID NOs: 302-317, 320-322, 324-327, 331, 332, or 487.

12. 8. The NARE of claim 7, comprising: (i) any one of SEQ ID NOs: 344-349, or 498; (ii) SEQ ID NO: 334 or SEQ ID NO: 342; and (iii) any one of SEQ ID NOs: 302-317, 320-322, 324-327, 331, 332, or 487.

13. 8. The NARE of claim 7, comprising: (i) a sequence that is at least 90% identical to SEQ ID NOs: 344-349, 498; (ii) a sequence that is at least 90% identical to SEQ ID NO: 334 or 342; and (iii) a sequence that is at least 90% identical to any one of SEQ ID NOs: 302-317, 320-322, 324-327, 331, or 332.

14. 8. The NARE of claim 7, comprising: (i) a sequence that is at least 95% identical to SEQ ID NOs: 344-349, 498; (ii) a sequence that is at least 95% identical to SEQ ID NO: 334 or 342; and (iii) a sequence that is at least 95% identical to any one of SEQ ID NOs: 302-317, 320-322, 324-327, 331, or 332.

15. 8. The NARE of claim 7, comprising any one of: (i) SEQ ID NOs: 344-349, 498; (ii) SEQ ID NO: 334 or 342; and (iii) SEQ ID NOs: 302-317, 320-322, 324-327, 331, or 332.

16. (i) a sequence that is at least 90% identical to any one of SEQ ID NOs: 344-349, or 498; (ii) a sequence that is at least 90% identical to any one of SEQ ID NOs: 351-356, 499, or 500; (iii) a sequence that is at least 90% identical to any one of SEQ ID NOs: 200, 370, 417-420, 502, 441, 482-485, 489, or 491-496; and (iv) optionally, a sequence that is at least 90% identical to any one of SEQ ID NOs: 444, 452, or 488; (v) optionally, a sequence that is at least 90% identical to SEQ ID NO: 402; and (vi) optionally, SEQ ID NO:

433.

17. 17. The NARE of claim 16, comprising: (i) a sequence that is at least 95% identical to any one of SEQ ID NOs: 344-349, or 498; (ii) a sequence that is at least 95% identical to any one of SEQ ID NOs: 351-356, 499, or 500; (iii) a sequence that is at least 95% identical to any one of SEQ ID NOs: 200, 370, 417-420, 502, 441, 482-485, 489, or 491-496; and (iv) optionally, a sequence that is at least 95% identical to any one of SEQ ID NOs: 444, 452, or 488; (v) optionally, a sequence that is at least 95% identical to SEQ ID NO: 402; and (vi) optionally, SEQ ID NO:

433.

18. 17. The NARE of claim 16, comprising: (i) any one of SEQ ID NOs: 344-349, or 498; (ii) any one of SEQ ID NOs: 351-356, 499, or 500; (iii) any one of SEQ ID NOs: 200, 370, 417-420, 502, 441, 482-485, 489, or 491-496; and (iv) optionally, any one of SEQ ID NOs: 444, 452, or 488; (v) optionally, SEQ ID NO: 402; and (vi) optionally, SEQ ID NO:

433.

19. 17. The NARE of claim 16, comprising: (i) a sequence that is at least 90% identical to any one of SEQ ID NOs: 344-349, or 498; (ii) a sequence that is at least 90% identical to any one of SEQ ID NOs: 351-356, 499, or 500; (iii) a sequence that is at least 90% identical to any one of SEQ ID NOs: 200, 370, 417-420, 502, 482-485, 489, or 491-496; and (iv) optionally, a sequence that is at least 90% identical to SEQ ID NO: 444 or 452.

20. 17. The NARE of claim 16, comprising: (i) a sequence that is at least 95% identical to any one of SEQ ID NOs: 344-349, or 498; (ii) a sequence that is at least 95% identical to any one of SEQ ID NOs: 351-356, 499, or 500; (iii) a sequence that is at least 95% identical to any one of SEQ ID NOs: 200, 370, 417-420, 502, 482-485, 489, or 491-496; and (iv) optionally, a sequence that is at least 95% identical to SEQ ID NO: 444 or 452.

21. 17. The NARE of claim 16, comprising: (i) any one of SEQ ID NOs: 344-349, 498; (ii) any one of SEQ ID NOs: 351-356, 499, or 500; (iii) any one of SEQ ID NOs: 200, 370, 417-420, 502, 482-485, 489, or 491-496; and (iv) optionally, SEQ ID NO: 444 or 452.

22. 17. The NARE of claim 16, comprising: (i) a sequence that is at least 90% identical to any one of SEQ ID NOs: 344-349, or 498; (ii) a sequence that is at least 90% identical to any one of SEQ ID NOs: 351-356, 499, or 500; (iii) a sequence that is at least 90% identical to any one of SEQ ID NOs: 200, 417-420, 502, or 485; and (iv) optionally, a sequence that is at least 90% identical to SEQ ID NO: 444 or 452.

23. 17. The NARE of claim 16, comprising: (i) a sequence that is at least 95% identical to any one of SEQ ID NOs: 344-349, or 498; (ii) a sequence that is at least 95% identical to any one of SEQ ID NOs: 351-356, 499, or 500; (iii) a sequence that is at least 95% identical to any one of SEQ ID NOs: 200, 417-420, 502, or 485; and (iv) optionally, a sequence that is at least 95% identical to SEQ ID NO: 444 or 452.

24. 17. The NARE of claim 16, comprising: (i) any one of SEQ ID NOs: 344-349, 498; (ii) any one of SEQ ID NOs: 351-356, 499, or 500; (iii) any one of SEQ ID NOs: 200, 417-420, 502, or 485; and (iv) optionally, SEQ ID NO: 444 or 452.

25. 17. The NARE of claim 16, comprising: (i) a sequence that is at least 90% identical to any one of SEQ ID NOs: 344-349, or 498; (ii) a sequence that is at least 90% identical to any one of SEQ ID NOs: 351-356, 499, or 500; and (iii) a sequence that is at least 90% identical to any one of SEQ ID NOs: 370, 482-484, 489, or 491-496.

26. 17. The NARE of claim 16, comprising: (i) a sequence that is at least 95% identical to any one of SEQ ID NOs: 344-349, or 498; (ii) a sequence that is at least 95% identical to any one of SEQ ID NOs: 351-356, 499, or 500; and (iii) a sequence that is at least 95% identical to any one of SEQ ID NOs: 370, 482-484, 489, or 491-496.

27. 17. The NARE of claim 16, comprising: (i) any one of SEQ ID NOs: 344-349, 498; (ii) any one of SEQ ID NOs: 351-356, 499, or 500; and (iii) any one of SEQ ID NOs: 370, 482-484, 489, or 491-496.

28. (i) a sequence that is at least 90% identical to any one of SEQ ID NOs: 344-349, or 498; (ii) a sequence that is at least 90% identical to SEQ ID NO: 335; and (iii) a sequence that is at least 90% identical to any one of SEQ ID NOs: 294, 295, 296, 299, 323, 328, 329, 330, 407, 501, 430, 431, 503, 434, or 504; and (iv) optionally, a sequence that is at least 90% identical to SEQ ID NO:

444.

29. 29. The NARE of claim 28, comprising: (i) a sequence that is at least 95% identical to any one of SEQ ID NOs: 344-349, or 498; (ii) a sequence that is at least 95% identical to SEQ ID NO: 335; and (iii) a sequence that is at least 95% identical to any one of SEQ ID NOs: 294, 295, 296, 299, 323, 328, 329, 330, 407, 501, 430, 431, 503, 434, or 504; and (iv) optionally, a sequence that is at least 95% identical to SEQ ID NO:

444.

30. 29. The NARE of claim 28, comprising: (i) any one of SEQ ID NOs: 344-349, or 498; (ii) SEQ ID NO: 335; and (iii) any one of SEQ ID NOs: 294, 295, 296, 299, 323, 328, 329, 330, 407, 501, 430, 431, 503, 434, or 504; and (iv) optionally, SEQ ID NO:

444.

31. 29. The NARE of claim 28, comprising: (i) a sequence that is at least 90% identical to any one of SEQ ID NOs: 344-349, or 498; (ii) a sequence that is at least 90% identical to SEQ ID NO: 335; and (iii) a sequence that is at least 90% identical to any one of SEQ ID NOs: 294, 295, 296, 407, 501, 430, 431, 503, 434, or 504; and (iv) a sequence that is at least 90% identical to SEQ ID NO:

444.

32. 29. The NARE of claim 28, comprising: (i) a sequence that is at least 95% identical to any one of SEQ ID NOs: 344-349, or 498; (ii) a sequence that is at least 95% identical to SEQ ID NO: 335; and (iii) a sequence that is at least 95% identical to any one of SEQ ID NOs: 294, 295, 296, 407, 501, 430, 431, 503, 434, or 504; and (iv) a sequence that is at least 95% identical to SEQ ID NO:

444.

33. 29. The NARE of claim 28, comprising: (i) any one of SEQ ID NOs: 344-349, or 498; (ii) SEQ ID NO: 335; and (iii) any one of SEQ ID NOs: 294, 295, 296, 407, 501, 430, 431, 503, 434, or 504; and (iv) SEQ ID NO:

444.

34. A NARE comprising (i) a sequence that is at least 90% identical to any one of SEQ ID NOs: 339, 363-369, 378, 379, 382, ​​385, 387-389, 391, 398, or 399, and (ii) a sequence that is at least 90% identical to any one of SEQ ID NOs: 430, 431, or 503.

35. 35. The NARE of claim 34, comprising (i) a sequence that is at least 95% identical to any one of SEQ ID NOs: 339, 363-369, 378, 379, 382, ​​385, 387-389, 391, 398, or 399, and (ii) a sequence that is at least 95% identical to any one of SEQ ID NOs: 430, 431, or 503.

36. 35. The NARE of claim 34, comprising: (i) any one of SEQ ID NOs: 339, 363-369, 378, 379, 382, ​​385, 387-389, 391, 398, or 399; and (ii) any one of SEQ ID NOs: 430, 431, or 503.

37. A NARE comprising a sequence that is at least 90% identical to any one of SEQ ID NOs: 138-161.

38. 38. The NARE of claim 37, comprising a sequence that is at least 95% identical to any one of SEQ ID NOs: 138-161.

39. The NARE of claim 37, comprising any one of SEQ ID NOs: 138-161.

40. A NARE comprising: (i) a sequence that is at least 90% identical to SEQ ID NO:298; (ii) a sequence that is at least 90% identical to SEQ ID NO:444; and (iii) optionally, a sequence that is at least 90% identical to SEQ ID NO:

475.

41. 41. The NARE of claim 40, comprising: (i) a sequence that is at least 95% identical to SEQ ID NO: 298; (ii) a sequence that is at least 95% identical to SEQ ID NO: 444; and (iii) optionally, a sequence that is at least 95% identical to SEQ ID NO:

475.

42. 41. The NARE of claim 40, comprising: (i) SEQ ID NO: 298; (ii) SEQ ID NO: 444; and (iii) optionally, SEQ ID NO:

475.

43. A NARE comprising: (i) a sequence that is at least 90% identical to any one of SEQ ID NOs: 339, 380, 383, 386, or 390; (ii) a sequence that is at least 90% identical to SEQ ID NO: 439 or 497; and (iii) optionally, a sequence that is at least 90% identical to SEQ ID NO:

444.

44. 44. The NARE of claim 43, comprising: (i) a sequence that is at least 95% identical to any one of SEQ ID NOs: 339, 380, 383, 386, or 390; (ii) a sequence that is at least 95% identical to SEQ ID NO: 439 or 497; and (iii) optionally, a sequence that is at least 95% identical to SEQ ID NO:

444.

45. 44. The NARE of claim 43, comprising: (i) any one of SEQ ID NOs: 339, 380, 383, 386, or 390; (ii) SEQ ID NO: 439 or 497; and (iii) optionally, SEQ ID NO:

444.

46. 44. The NARE of claim 43, comprising (i) a sequence that is at least 90% identical to any one of SEQ ID NOs: 339, 380, 383, 386, or 390, and (ii) a sequence that is at least 90% identical to SEQ ID NO: 439 or 497.

47. 44. The NARE of claim 43, comprising (i) a sequence that is at least 95% identical to any one of SEQ ID NOs: 339, 380, 383, 386, or 390, and (ii) a sequence that is at least 95% identical to SEQ ID NO: 439 or 497.

48. 44. The NARE of claim 43, comprising: (i) any one of SEQ ID NOs: 339, 380, 383, 386, or 390; and (ii) SEQ ID NO: 439 or 497.

49. A NARE comprising: (i) a sequence that is at least 90% identical to any one of SEQ ID NOs: 344-349, or 498; (ii) a sequence that is at least 90% identical to SEQ ID NO: 336; and (iii) a sequence that is at least 90% identical to any one of SEQ ID NOs: 201, 284, 285, 301, 362, 372, 373, 403-406, 408-410, 412, 427, 444, 453-456, 486, or 490.

50. 50. The NARE of claim 49, comprising: (i) a sequence that is at least 95% identical to any one of SEQ ID NOs: 344-349, or 498; (ii) a sequence that is at least 95% identical to SEQ ID NO: 336; and (iii) a sequence that is at least 95% identical to any one of SEQ ID NOs: 201, 284, 285, 301, 362, 372, 373, 403-406, 408-410, 412, 427, 444, 453-456, 486, or 490.

51. 50. The NARE of claim 49, comprising: (i) any one of SEQ ID NOs: 344-349, or 498; (ii) SEQ ID NO: 336; and (iii) any one of SEQ ID NOs: 201, 284, 285, 301, 362, 372, 373, 403-406, 408-410, 412, 427, 444, 453-456, 486, or 490.

52. (i) a sequence that is at least 90% identical to any one of SEQ ID NOs: 374-376; (ii) optionally, a sequence that is at least 90% identical to any one of SEQ ID NOs: 344-349, 498, or 393; (iii) a sequence that is at least 90% identical to any one of SEQ ID NOs: 93-98, 103, 109, 128-136, 195-198, 201, 284, 285, 301, 362, 371, 373, 403-406, 408-410, 412, 417-420, 502, 427, 453-456, 460-474, 486, or 490; and (iv) optionally, a sequence that is at least 90% identical to SEQ ID NO: 443 or 448.

53. 53. The NARE of claim 52, comprising: (i) a sequence that is at least 95% identical to any one of SEQ ID NOs: 374-376; (ii) optionally, a sequence that is at least 95% identical to any one of SEQ ID NOs: 344-349, 498, or 393; (iii) a sequence that is at least 95% identical to any one of SEQ ID NOs: 93-98, 103, 109, 128-136, 195-198, 201, 284, 285, 301, 362, 371, 373, 403-406, 408-410, 412, 417-420, 502, 427, 453-456, 460-474, 486, or 490; and (iv) optionally, a sequence that is at least 95% identical to SEQ ID NO: 443 or 448.

54. 53. The NARE of claim 52, comprising: (i) any one of SEQ ID NOs: 374-376; (ii) optionally any one of SEQ ID NOs: 344-349, 498, or 393; (iii) any one of SEQ ID NOs: 93-98, 103, 109, 128-136, 195-198, 201, 284, 285, 301, 362, 371, 373, 403-406, 408-410, 412, 417-420, 502, 427, 453-456, 460-474, 486, or 490; and (iv) optionally, SEQ ID NO: 443 or 448.

55. 53. The NARE of claim 52, comprising (i) a sequence that is at least 90% identical to any one of SEQ ID NOs: 374-376, and (ii) a sequence that is at least 90% identical to any one of SEQ ID NOs: 93-98, 103, 109, 128-136, 195-198, 201, 284, 285, 301, 362, 371, 373, 403-406, 408-410, 412, 427, 453-456, 460-474, 486, or 490.

56. 53. The NARE of claim 52, comprising (i) a sequence that is at least 95% identical to any one of SEQ ID NOs: 374-376, and (ii) a sequence that is at least 95% identical to any one of SEQ ID NOs: 93-98, 103, 109, 128-136, 195-198, 201, 284, 285, 301, 362, 371, 373, 403-406, 408-410, 412, 427, 453-456, 460-474, 486, or 490.

57. 53. The NARE of claim 52, comprising: (i) any one of SEQ ID NOs: 374-376; and (ii) any one of SEQ ID NOs: 93-98, 103, 109, 128-136, 195-198, 201, 284, 285, 301, 362, 371, 373, 403-406, 408-410, 412, 427, 453-456, 460-474, 486, or 490.

58. 53. The NARE of claim 52, comprising (i) a sequence that is at least 90% identical to any one of SEQ ID NOs: 374-376, and (ii) a sequence that is at least 90% identical to any one of SEQ ID NOs: 201, 284, 285, 301, 362, 371, 373, 403-406, 408-410, 412, 427, 453-456, 486, or 490.

59. 53. The NARE of claim 52, comprising (i) a sequence that is at least 95% identical to any one of SEQ ID NOs: 374-376, and (ii) a sequence that is at least 95% identical to any one of SEQ ID NOs: 201, 284, 285, 301, 362, 371, 373, 403-406, 408-410, 412, 427, 453-456, 486, or 490.

60. 53. The NARE of claim 52, comprising: (i) any one of SEQ ID NOs: 374-376; and (ii) any one of SEQ ID NOs: 201, 284, 285, 301, 362, 371, 373, 403-406, 408-410, 412, 427, 453-456, 486, or 490.

61. 53. The NARE of claim 52, comprising (i) a sequence that is at least 90% identical to any one of SEQ ID NOs: 374-376, and (ii) a sequence that is at least 90% identical to any one of SEQ ID NOs: 93-98, 103, 109, 128-136, 195-198, or 460-474.

62. 53. The NARE of claim 52, comprising (i) a sequence that is at least 95% identical to any one of SEQ ID NOs: 374-376, and (ii) a sequence that is at least 95% identical to any one of SEQ ID NOs: 93-98, 103, 109, 128-136, 195-198, or 460-474.

63. 53. The NARE of claim 52, comprising: (i) any one of SEQ ID NOs: 374-376; and (ii) any one of SEQ ID NOs: 93-98, 103, 109, 128-136, 195-198, or 460-474.

64. 53. The NARE of claim 52, comprising: (i) a sequence that is at least 90% identical to any one of SEQ ID NOs: 344-349, 498, or 393; (ii) a sequence that is at least 90% identical to any one of SEQ ID NOs: 374-376; (iii) a sequence that is at least 90% identical to any one of SEQ ID NOs: 417-420, or 502; and (iv) optionally, a sequence that is at least 90% identical to SEQ ID NO: 443 or 448.

65. 53. The NARE of claim 52, comprising: (i) a sequence that is at least 95% identical to any one of SEQ ID NOs: 344-349, 498, or 393; (ii) a sequence that is at least 95% identical to any one of SEQ ID NOs: 374-376; (iii) a sequence that is at least 95% identical to any one of SEQ ID NOs: 417-420, or 502; and (iv) optionally, a sequence that is at least 95% identical to SEQ ID NO: 443 or 448.

66. 53. The NARE of claim 52, comprising: (i) any one of SEQ ID NOs: 344-349, 498, or 393; (ii) any one of SEQ ID NOs: 374-376; (iii) any one of SEQ ID NOs: 417-420, or 502; and (iv) optionally, SEQ ID NO: 443 or 448.

67. A NARE comprising: (i) a sequence that is at least 90% identical to SEQ ID NO: 478 or 479; (ii) a sequence that is at least 90% identical to SEQ ID NO: 350; (iii) a sequence that is at least 90% identical to any one of SEQ ID NOs: 351-356, 499, or 500; and (iv) a sequence that is at least 90% identical to any one of SEQ ID NOs: 361, 421, 422, 423, 428, 444, or 480.

68. 68. The NARE of claim 67, comprising: (i) a sequence that is at least 95% identical to SEQ ID NO: 478 or 479; (ii) a sequence that is at least 95% identical to SEQ ID NO: 350; (iii) a sequence that is at least 95% identical to any one of SEQ ID NOs: 351-356, 499, or 500; and (iv) a sequence that is at least 95% identical to any one of SEQ ID NOs: 361, 421, 422, 423, 428, 444, or 480.

69. 68. The NARE of claim 67, comprising: (i) SEQ ID NO: 478 or 479; (ii) SEQ ID NO: 350; (iii) any one of SEQ ID NOs: 351-356, 499, or 500; and (iv) any one of SEQ ID NOs: 361, 421, 422, 423, 428, 444, or 480.

70. A NARE comprising (i) a sequence that is at least 90% identical to SEQ ID NO: 377, and (ii) a sequence that is at least 90% identical to any one of SEQ ID NOs: 444, 457, 458, 469, or 470.

71. 71. The NARE of claim 70, comprising (i) a sequence that is at least 95% identical to SEQ ID NO: 377, and (ii) a sequence that is at least 95% identical to any one of SEQ ID NOs: 444, 457, 458, 469, or 470.

72. 71. The NARE of claim 70, comprising: (i) SEQ ID NO: 377; and (ii) any one of SEQ ID NOs: 444, 457, 458, 469, or 470.

73. A NARE comprising (i) a sequence that is at least 90% identical to any one of SEQ ID NOs: 199, 476, or 477, and (ii) a sequence that is at least 90% identical to SEQ ID NO:

300.

74. 74. The NARE of claim 73, comprising (i) a sequence that is at least 95% identical to any one of SEQ ID NOs: 199, 476, or 477, and (ii) a sequence that is at least 95% identical to SEQ ID NO:

300.

75. 74. The NARE of claim 73, comprising: (i) any one of SEQ ID NOs: 199, 476, or 477; and (ii) SEQ ID NO:

300.

76. A NARE comprising: (i) a sequence that is at least 90% identical to SEQ ID NO:474; (ii) a sequence that is at least 90% identical to SEQ ID NO:340 or 341; and (iii) optionally, a sequence that is at least 90% identical to SEQ ID NO:

393.

77. 77. The NARE of claim 76, comprising: (i) a sequence that is at least 95% identical to SEQ ID NO: 474; (ii) a sequence that is at least 95% identical to SEQ ID NO: 340 or 341; and (iii) optionally, a sequence that is at least 95% identical to SEQ ID NO:

393.

78. 77. The NARE of claim 76, comprising: (i) number 474; (ii) SEQ ID NO: 340 or 341; and (iii) optionally, SEQ ID NO:

393.

79. A NARE comprising a sequence that is at least 90% identical to any one of SEQ ID NOs: 6, 7, 9-12, 14, 16-18, 21-32, 34, 37-91, 99-102, 104-108, 110-127, 138-194, 202-283, or 286-293.

80. 80. The NARE of claim 79, comprising a sequence that is at least 95% identical to any one of SEQ ID NOs: 6, 7, 9-12, 14, 16-18, 21-32, 34, 37-91, 99-102, 104-108, 110-127, 138-194, 202-283, or 286-293.

81. 80. The NARE of claim 79, comprising any one of SEQ ID NOs: 6, 7, 9-12, 14, 16-18, 21-32, 34, 37-91, 99-102, 104-108, 110-127, 138-194, 202-283, or 286-293.

82. 80. The NARE of claim 79, comprising a sequence that is at least 90% identical to any one of SEQ ID NOs: 6, 14, 16, 18, 34, 48, 104-107, 162-172, 179, 180, 183, 184, or 293.

83. 80. The NARE of claim 79, comprising a sequence that is at least 95% identical to any one of SEQ ID NOs: 6, 14, 16, 18, 34, 48, 104-107, 162-172, 179, 180, 183, 184, or 293.

84. 80. The NARE of claim 79, comprising any one of SEQ ID NOs: 6, 14, 16, 18, 34, 48, 104-107, 162-172, 179, 180, 183, 184, or 293.

85. An expression construct comprising a NARE according to any one of claims 1 to 84 and an operably linked transgene.

86. 86. The expression construct of claim 85, further comprising a polyadenylation sequence.

87. 86. A vector comprising the expression construct of claim 85.

88. 88. The vector of claim 87, wherein the vector is a non-viral vector.

89. 88. The vector of claim 87, wherein the vector is a viral vector.

90. 90. The vector of claim 89, wherein the vector is an adeno-associated virus (AAV) vector.

91. 86. A vector comprising a nucleic acid sequence comprising: (i) an expression construct according to 85; and (ii) one or more inverted terminal repeats (ITRs).

92. 92. The vector of claim 91, wherein the nucleic acid sequence comprises a 5' ITR and a 3' ITR.

93. 93. The vector of claim 92, wherein the 5' ITR and the 3' ITR are derived from AAV serotype AAV2.

94. A cell comprising an expression construct according to claim 84 or a vector according to any one of claims 87 to 93.

95. 95. The cell of claim 94, wherein the cell is a nerve cell, a muscle cell, or a liver cell.

96. 94. A pharmaceutical composition comprising: (i) the expression construct of claim 85 or the vector of any one of claims 87 to 93; and (ii) a pharmaceutically acceptable excipient.

97. A method for expressing a transgene in a cell comprising an expression construct according to claim 85 or a vector according to any one of claims 87 to 93.

98. A method for regulating transgene expression in a cell comprising an expression construct according to claim 84 or a vector according to any one of claims 86 to 93.

99. 99. The method of claim 97 or 98, wherein the cell is a nerve cell, a muscle cell, or a liver cell.

Images