Data encodable compositions and methods of use and manufacture

Abstract

Provided herein are compositions and methods related to polymers comprising a plurality of subunits, wherein a first subunit of the comprises more than one convertible residue, a second subunit does not comprise a convertible residue and each subunit comprises at least 30 residues.

Description

DATA ENCODABLE COMPOSITIONS AND METHODS OF USE ANDMANUFACTURECROSS-REFERENCE

[0001] This application claims priority to U.S. Provisional Patent Application No. 63 / 513,801, filed July 14, 2023, which applications are herein incorporated by reference in their entireties for all purposes.BACKGROUND

[0002] Polymers may comprise a variety of components. Polymers may be used for data storage.SUMMARY

[0003] In an aspect, the present disclosure provides a polymer comprising a plurality of subunits, wherein: (a) a first subunit of the plurality of subunits comprises at least 10 convertible residues, wherein the at least 10 convertible residues are in a first state and are configured to transition irreversibly into a second state upon application of a stimulus; (b) a second subunit of the plurality of subunits does not comprise any convertible residues; and (c) each subunit of the plurality of subunits comprises at least 30 residues.

[0004] In some embodiments, the comprises nucleic acid. In some embodiments, the second subunit lacks one of guanine (G), cytosine (C), thymine (T), or adenosine (A). In some embodiments, a convertible residue of the at least 10 convertible residues comprises a photo- modifiable group. In some embodiments, the photo-modifiable group comprises a dye modification. In some embodiments, a convertible residue of the at least 10 convertible residues comprises a T. In some embodiments, the dye modification is connected to the T with a first linker. In some embodiments, the first linker comprises a 1,2, 3, -triazole ring, an ethylene, a methylene, an ether, an amide, a phosphodiester, or a thioether. In some embodiments, the first subunit comprises at least 60 nucleotides. In some embodiments, the first subunit comprises a GC content of 30-70%. In some embodiments, the stimulus comprises light. In some embodiments, the first subunit comprises a cleavable site. In some embodiments, the cleavable site is a restriction site. In some embodiments, the restriction site is cleavable by a golden gate assembly nuclease. In some embodiments, the second nucleic acid comprises at least 60 nucleotides. In some embodiments, the plurality of subunits comprises at least 50 subunits. In some embodiments, the plurality of the subunits comprises at least 50 copies of the first subunit. In some embodiments, the plurality of the subunits comprises at least 50 copies of the secondsubunit. In some embodiments, each copy of the first subunit is separated by at least one copy of the second subunit. In some embodiments, each copy of the second subunit is separated by at least one copy of the first subunit. In some embodiments, the polymer comprises at least 10k residues. In some embodiments, the residues are nucleotides. In some embodiments, each subunit of the plurality of subunits is connected through a linker selected from the group consisting of 1,2, 3, -triazole ring, an ethylene, a methylene, an ether, an amide, a phosphodiester, or a thioether.

[0005] In another aspect, the present disclosure provides a polymer comprising a plurality of subunits, wherein: (a) a first subunit of the plurality of subunits comprises at least 10 convertible residues, wherein the at least 10 convertible residues: (i) are in a first state; (ii) are spaced evenly within the first subunit; and (iii) are configured to transition into a second state upon application of a stimulus; (b) a second subunit of the plurality of subunits does not comprise any convertible residues; and (c) each subunit of the plurality of subunits comprises at least 30 residues.

[0006] In some embodiments, each convertible residue of the at least 10 convertible residues is separated by at least 1 non-convertible residue, wherein the at least 1 non-convertible residue does not change upon application of a stimulus. In some embodiments, the at least 1 nonconvertible residue comprises a nucleotide. In some embodiments, the polymer comprises nucleic acid. In some embodiments, the second subunit lacks one of: guanine (G), cytosine (C), thymine (T), or adenosine (A). In some embodiments, a convertible residue of the at least 10 convertible residues comprises a photo-modifiable group. In some embodiments, the photo- modifiable group, comprises a dye modification. In some embodiments, a convertible residue of the at least 10 convertible residues comprises a T. In some embodiments, the dye modification is connected to the T with a first linker. In some embodiments, the first linker comprises a 1,2,3,- triazole ring, an ethylene, a methylene, an ether, an amide, a phosphodiester, or a thioether. In some embodiments, the first subunit comprises at least 60 nucleotides. In some embodiments, the first subunit comprises a GC content of 30-70%. In some embodiments, the first subunit comprises a cleavable site. In some embodiments, the cleavable site is a restriction site. In some embodiments, the restriction site is cleavable by a golden gate assembly nuclease. In some embodiments, the second nucleic acid comprises at least 60 nucleotides. In some embodiments, the plurality of subunits comprises at least 50 subunits. In some embodiments, the plurality of the subunits comprises at least 50 copies of the first subunit. In some embodiments, the plurality of the subunits comprises at least 50 copies of the second subunit. In some embodiments, each copy of the first subunit is separated by at least one copy of the second subunit. In some embodiments, each copy of the second subunit is separated by at least one copy of the first subunit. In someembodiments, the polymer comprises at least 10k residues. In some embodiments, residues are nucleotides. In some embodiments, each subunit of the plurality of subunits is connected through a linker selected from the group consisting of 1,2, 3, -triazole ring, an ethylene, a methylene, an ether, an amide, a phosphodiester, or a thioether.

[0007] In another aspect, the present disclosure provides a polymer comprising a plurality of subunits, wherein: (a) a first subunit of the plurality of subunits comprises at least 10 convertible residues, wherein each of the at least 10 convertible residues comprise a photo-modifiable group;(b) a second subunit of the plurality of subunits does not comprise any convertible residues; and(c) each subunit of the plurality of subunits comprises at least 30 residues.

[0008] In some embodiments, the photo-modifiable group comprises a dye modification. In some embodiments, the dye modification comprises a Cy3 modification. In some embodiments, the dye modification comprises a Cy5 modification. In some embodiments, the polymer comprises nucleic acid. In some embodiments, the second subunit lacks one of: guanine (G), cytosine (C), thymine (T), or adenosine (A). In some embodiments, a convertible residue of the at least 10 convertible residues comprises a photo-modifiable group. In some embodiments, the photo-modifiable group, comprises a dye modification. In some embodiments, a convertible residue of the at least 10 convertible residues comprises a T. In some embodiments, the dye modification is connected to the T with a first linker. In some embodiments, the first linker comprises a 1,2, 3, -triazole ring, an ethylene, a methylene, an ether, an amide, a phosphodiester, or a thioether. In some embodiments, the first subunit comprises at least 60 nucleotides. In some embodiments, the first subunit comprises a GC content of 30-70%. In some embodiments, the stimulus comprises light. In some embodiments, the first subunit comprises a cleavable site. In some embodiments, the restriction site is cleavable by a golden gate assembly nuclease. In some embodiments, the second subunit comprises at least 60 nucleotides. In some embodiments, the plurality of subunits comprises at least 50 subunits. In some embodiments, the plurality of the subunits comprises at least 50 copies of the first subunit. In some embodiments, the plurality of the subunits comprises at least 50 copies of the second subunit. In some embodiments, each copy of the first subunit is separated by at least one copy of the second subunit. In some embodiments, teach copy of the second subunit is separated by at least one copy of the first subunit. In some embodiments, the polymer comprises at least 10k residues. In some embodiments, the residues are nucleotides. In some embodiments, each subunit of the plurality of subunits is connected through a linker selected from the group consisting of 1,2, 3, -triazole ring, an ethylene, a methylene, an ether, an amide, a phosphodiester, or a thioether.

[0009] In another aspect, the present disclosure provides a method of comprising: (a) providing a polymer comprising a plurality of subunits, wherein (i) a first subunit of the plurality of subunits comprises at least 10 convertible residues, wherein the at least 10 convertible residues are in a first state and transition irreversibly into a second state upon application of a stimulus; (ii) a second subunit of the plurality of subunits comprises non-convertible residues and does not comprise any convertible residues, wherein the non-convertible residues do not change upon application of a stimulus; and (iii) each subunit of the plurality of subunits comprises at least 30 residues; and (b) applying the stimulus to the first subunit of the plurality of subunits, thereby causing at least a portion of the at least 10 convertible residues to irreversibly transition into a second state.

[0010] In some embodiments, the at least 10 convertible residues are spaced evenly within the first subunit. In some embodiments, each of the at least 10 convertible residues comprise a photo-modifiable group. In some embodiments, the photo-modifiable group comprises a dye modification. In some embodiments, (b) comprises applying a light to the first subunit. In some embodiments, the polymer comprises a nucleic acid. In some embodiments, the second subunit lacks one of: guanine (G), cytosine (C), thymine (T), or adenosine (A). In some embodiments, a convertible residue of the at least 10 convertible residues comprises a T. In some embodiments, the first subunit comprises at least 60 nucleotides. In some embodiments, the first subunit comprises a GC content of 30-70%. In some embodiments, the first subunit comprises a cleavable site. In some embodiments, the cleavable site is a restriction site.

[0011] In another aspect, the present disclosure provides a writable polymer comprising a plurality of subunits across the length of the writable polymer, each subunit comprising a first section and a second section 3’ to the first section, wherein the first section is composed of up to three different nucleobases, and the second section comprises at least a fourth nucleobase different from the nucleobases in the first section.

[0012] In some embodiments, the first sections of the plurality of subunits have the same length and / or composition of nucleobases. In some embodiments, the second sections of the plurality of subunits have the same length and / or composition of nucleobases. In some embodiments, the second sections of the plurality of subunits have a different length and / or a different composition of nucleobases. In some embodiments, the second sections of the plurality of subunits comprise a T nucleobase. In some embodiments, the second sections of the plurality of subunits comprise a U nucleobase. In some embodiments, the first sections of the plurality of subunits comprises a GC ratio of about 40%-60%. In some embodiments, the first sections of the plurality of subunits comprises a GC ratio of about 50%. In some embodiments, the first sections of theplurality of subunits does not include a homopolymer longer than a 14-mer. In some embodiments, the first sections of the plurality of subunits do not include a homopolymer longer than a 7-mer. In some embodiments, the first sections of the plurality of subunits comprises up to 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, 50, 60, 70, 80, 90, or 100 nucleobases. In some embodiments, the first section is composed of two different nucleobases. In some embodiments, the polymer subunits comprises a sequence defined by [(Y)n(X)m]p, wherein Y comprises a plurality of nucleobase selected from A / C / G, and X comprises a fourth nucleobase not selected from A / C / G. In some embodiments, n is less than 100, 50, 28, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, or 3. In some embodiments, n is at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 13, 14, 27, 28, 49, 50, 99, or 100. In some embodiments, n is 3-100. In some embodiments, m is less than 3. In some embodiments, m is at least 2. In some embodiments, p is at least 3, 4, 5, 6, 7, 8, 9, 10, 100, 500, 1,000, 5,000, 10,000, 50,000, or 100,000. In some embodiments, n=l, m=l, and p>10, 100, 500, 1000, 5000, 10,000, 50,000, or 100,000. In some embodiments, Y is the first section of polymer subunits, and X is the second section of the polymer subunits. In some embodiments, X is a single fourth nucleobase not selected from A / C / G, m is 1, and p is 1 (e.g., [(A / C / G)nT]). In some embodiments, the second section is repeated at an interval defined by a length of the first section. In some embodiments, the length of each first section is defined by a maximum variation being less than 0.3, the maximum variation being equal to a median absolute deviation of the length of the first sections divided by a median length of the first sections. In some embodiments, the length of each first section is from 4-100 bp. In some embodiments, the length of each first section is up to 100 bp. In some embodiments, the polymer subunits define at least 90%, 95%, 98%, or 99% of the polymer. In some embodiments, the polymer further comprises a sequence specific cleavable site at a 5’ end of a 5’ outermost subunit and / or a 3’ end of a 3’ outermost subunit. In some embodiments, the polymer further comprises a sequence specific cleavable site at each of the 5’ and 3’ ends of each subunit. In some embodiments, the polymer further comprises a second sequence specific cleavable site at the 5’ end of the 5’ outermost subunit. In some embodiments, the sequence specific cleavable site can be cut by an endonuclease that cuts only one of two strands of DNA. In some embodiments, the second sequence specific cleavable site can be cut by an endonuclease that cuts both strands of DNA. In some embodiments, the sequence specific cleavable site can be cut by a golden gate assembly endonuclease. In some embodiments, the second section comprises an irreversibly convertible moiety. In some embodiments, the irreversibly convertible moiety is attached to the fourth nucleobase in the second section. In some embodiments, the irreversibly convertible moiety is attached only to the fourth nucleobase in the second section. In some embodiments, the irreversibly convertiblemoiety is light activated, redox activated or chemically activated. In some embodiments, the irreversibly convertible moiety comprises fluorescein, CF488A, ATTO488, Alexa Fluor 488, Cy3, Alexa Fluor 546, Alexa Fluor 555, ATTO643, ATTO647N, ATTO655, or Cy5. In some embodiments, the irreversibly convertible moiety comprises uber dye. In some embodiments, the irreversibly convertible moiety comprises azido dye conjugated to the DNA with click chemistry. In some embodiments, the first section does not include an irreversibly convertible moiety. In some embodiments, the polymer is at least 10k, 20, 30k, 40k, 50k, 60k, 70k, 80k, 90k, or 100k units in length. In some embodiments, the polymer encodes at least 100, 200, 300, or 350 bits of binary data. In some embodiments, the polymer comprises at least 250 irreversibly convertible moieties.

[0013] In another aspect, the present disclosure provides a plurality of polymers. In some embodiments, the polymers of the plurality of polymers are at least 7 kbp in length and the composition does not comprise greater than 5%, 3%, or 1% of truncated polymers less than 7 kbp in length.

[0014] In another aspect, the present disclosure provides a plurality of polymers. In some embodiments, the polymers of the plurality of polymers are at least 7 kbp in length, wherein a length of the first sections of the polymer subunits is substantially the same in of the polymers.

[0015] In another aspect, the present disclosure provides a plurality of polymers. In some embodiments, the polymers of the plurality of polymers are at least 7 kbp in length, wherein a maximum variation of a length of the plurality of polymers does not exceed 10%, 5%, or 1%.

[0016] In another aspect, the present disclosure provides a plurality of polymers. In some embodiments, the polymers of the plurality of polymers are at least 7 kbp in length, there is at least 95%, 98%, or 99% similarity between the sequence of each of the plurality of polymers.

[0017] In another aspect, the present disclosure provides a method for manufacturing a writable polymer comprising: combining a plurality of the polymers described herein to create an extended polymer.

[0018] In some embodiments, the assembling comprises combining at least 10, 100, 1,000, or 10,000. In some embodiments, the method further comprises providing a destination vector comprising a sequence specific cleavable site that can be cut by an endonuclease that cuts both strands of DNA. In some embodiments, the method further comprises contacting the destination vector and the plurality of the polymers of claims 1-33 with an endonuclease that cuts both strands of DNA and which leaves a nucleotide overhang at the cleavage site, to produce a plurality of linearized fragments. In some embodiments, the method further comprises hybridizing the plurality of linearized fragments at the nucleotide overhangs to produce aplurality of hybridized fragments. In some embodiments, the method further comprises contacting the plurality of hybridized fragments with a ligase and ligating the plurality of hybridized fragments, thereby combining the plurality of the polymers of described herein to create the extended polymer. In some embodiments, the extended polymer is at least 7 kbp in length. The method of claim 49, further comprising combining a second plurality of the polymers of claims 1-33 with the extended polymer to produce a second extended polymer. In some embodiments, the method further comprises contacting the extended polymer and the second plurality of the polymers of the polymers described herein with an endonuclease that cuts both strands of DNA and which leaves a nucleotide overhang at the cleavage site, to produce a plurality of linearized fragments. In some embodiments, the method further comprises hybridizing the plurality of linearized fragments at the nucleotide overhangs to produce a plurality of hybridized fragments. In some embodiments, contacting the plurality of hybridized fragments with a ligase and ligating the plurality of hybridized fragments, thereby combining the second plurality of the polymers of the polymers described herein with the extended polymer to produce the second extended polymer. In some embodiments, the second extended polymer is at least 10 kbp, 20 kbp, 30 kbp, 40 kbp, 50 kbp, 75 kbp, 100 kbp, 150 kbp, or 200 kbp in length. In some embodiments, the method further comprises contacting the first or the second extended polymer with an endonuclease that cuts only one of two strands of DNA to produce a polymer comprising a nick site. In some embodiments, the nick site is 5’ of at least one polymer subunit. In some embodiments, the method further comprises contacting the polymer comprising the nick site with a DNA polymerase and synthesizing a new polymer. In some embodiments, the DNA polymerase incorporates an irreversibly convertible moiety the second section of the new polymer, wherein the new polymer is the polymer of any of the methods described herein.

[0019] Another aspect of the present disclosure provides a non-transitory computer readable medium comprising machine executable code that, upon execution by one or more computer processors, implements any of the methods above or elsewhere herein.

[0020] Another aspect of the present disclosure provides a system comprising one or more computer processors and computer memory coupled thereto. The computer memory comprises machine executable code that, upon execution by the one or more computer processors, implements any of the methods above or elsewhere herein.

[0021] Additional aspects and advantages of the present disclosure will become readily apparent to those skilled in this art from the following detailed description, wherein only illustrative embodiments of the present disclosure are shown and described. As will be realized, the present disclosure is capable of other and different embodiments, and its several details arecapable of modifications in various obvious respects, all without departing from the disclosure. Accordingly, the drawings and description are to be regarded as illustrative in nature, and not as restrictive.INCORPORATION BY REFERENCE

[0022] All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference. To the extent publications and patents or patent applications incorporated by reference contradict the disclosure contained in the specification, the specification is intended to supersede and / or take precedence over any such contradictory material.BRIEF DESCRIPTION OF THE DRAWINGS

[0023] The novel features of the invention are set forth with particularity in the appended claims. A better understanding of the features and advantages of the present invention will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the invention are utilized, and the accompanying drawings (also “Figure” and “FIG.” herein), of which:

[0024] FIG. 1 schematically illustrates subsections or building blocks of a DNA polymer molecule, according to the embodiments of the present disclosure;

[0025] FIG. 2 schematically illustrates Golden Gate assembly of a plurality of DNA subunits and a destination vector, according to the embodiments of the present disclosure;

[0026] FIG. 3 schematically illustrates a second stage Golden Gate assembly of a long DNA polymer molecule using the output polymers from FIG. 2 as input reagents for the second stage, according to the embodiments of the present disclosure ;

[0027] FIG. 4 schematically illustrates an example of dual labeling of a DNA polymer with nick translation incorporating two different chemically modifiable moi eties (e.g., Fluorescein and Cy5 fluorophores) into the DNA polymer along its length, according to the embodiments of the present disclosure;

[0028] FIG. 5 schematically illustrates example of alternative labeling methods to link chemically modifiable moi eties (e.g., dyes) to DNA polymers, according to the embodiments of the present disclosure;

[0029] FIG. 6 shows fluorescent images of stretched and labeled DNA polymers visualized using a fluorescent microscope and a camera, illustrating a 28 kb DNA polymer at panel A, a 36 kb DNA polymer at panel B, and a 40 kb DNA polymer at panel C;

[0030] FIG. 7 illustrates assembly of a DNA polymer according to the embodiments of the present disclosure;

[0031] FIG. 8 illustrates an example of a writable DNA polymer which has been written with data in chemically modifiable moi eties using light (e.g., fluorophores), and a graph measuring the fluorescence about the length of the DNA polymer, according to the embodiments of the present disclosure;

[0032] FIG. 9 schematically illustrates an example of a DNA polymer with the string “NAIO!” stored on the polymer in binary code, according to the embodiments of the present disclosure;

[0033] FIG. 10 shows graphs demonstrating selective local photobleaching of a writable DNA polymer labeled with two different chemically modifiable moi eties (e.g., Fluorescein on the 3’ to 5’ strand, and Cy5 fluorophores on the reverse complement strand).

[0034] FIG. 11 shows a computer system that is programmed or otherwise configured to implement methods provided herein.DETAILED DESCRIPTION

[0035] While various embodiments of the invention have been shown and described herein, it will be obvious to those skilled in the art that such embodiments are provided by way of example only. Numerous variations, changes, and substitutions may occur to those skilled in the art without departing from the invention. It should be understood that various alternatives to the embodiments of the invention described herein may be employed.

[0036] Whenever the term “at least,” “greater than,” or “greater than or equal to” precedes the first numerical value in a series of two or more numerical values, the term “at least,” “greater than” or “greater than or equal to” applies to each of the numerical values in that series of numerical values. For example, greater than or equal to 1, 2, or 3 is equivalent to greater than or equal to 1, greater than or equal to 2, or greater than or equal to 3.

[0037] Whenever the term “no more than,” “less than,” or “less than or equal to” precedes the first numerical value in a series of two or more numerical values, the term “no more than,” “less than,” or “less than or equal to” applies to each of the numerical values in that series of numerical values. For example, less than or equal to 3, 2, or 1 is equivalent to less than or equal to 3, less than or equal to 2, or less than or equal to 1.

[0038] An aspect of the disclosure provides a polymer. The polymer comprises a plurality of subunits, wherein: (a) a first subunit of the plurality of subunits comprises at least 10 convertible residues, wherein the at least 10 convertible residues are in a first state and are configured to transition irreversibly into a second state upon application of a stimulus; (b) a second subunit ofsaid plurality of subunits does not comprise any convertible residues; and (c) each subunit of the plurality of subunits comprises at least 30 residues.

[0039] The stimulus may comprise a variety of formats and may be applied in a variety of ways. In some cases, the stimulus may comprise light exposure, temperature exposure, one or more chemical reactions, or a combination thereof. The light exposure may comprise exposing the polymer to one or more wavelengths of light. The wavelength of light may comprise a wavelength of at least about 200 nanometers (nm), at least about 210 nm, at least about 220 nm, at least about 230 nm, at least about 240 nm, at least about 250 nm, at least about 260 nm, at least about 270 nm, at least about 280 nm, at least about 290 nm, at least about 300 nm, at least about 310 nm, at least about 320 nm, at least about 330 nm, at least about 340 nm, at least about 350 nm, at least about 360 nm, at least about 370 nm, at least about 380 nm, at least about 390 nm, at least about 400 nm, at least about 410 nm, at least about 420 nm, at least about 430 nm, at least about 440 nm, at least about 450 nm, at least about 460 nm, at least about 470 nm, at least about 480 nm, at least about 490 nm, at least about 500 nm, at least about 510 nm, at least about 520 nm, at least about 530 nm, at least about 540 nm, at least about 550 nm, at least about 560 nm, at least about 570 nm, at least about 580 nm, at least about 590 nm, at least about 600 nm, at least about 610 nm, at least about 620 nm, at least about 630 nm, at least about 640 nm, at least about 650 nm, at least about 660 nm, at least about 670 nm, at least about 680 nm, at least about 690 nm, at least about 700 nm, at least about 710 nm, at least about 720 nm, at least about 730 nm, at least about 740 nm, at least about 750 nm, at least about 760 nm, at least about 770 nm, at least about 780 nm, at least about 790 nm, at least about 800 nm, at least about 810 nm, at least about 820 nm, at least about 830 nm, at least about 840 nm, at least about 850 nm, or more. The wavelength of light may comprise a wavelength of at most about 200 nanometers (nm), at most about 210 nm, at most about 220 nm, at most about 230 nm, at most about 240 nm, at most about 250 nm, at most about 260 nm, at most about 270 nm, at most about 280 nm, at most about 290 nm, at most about 300 nm, at most about 310 nm, at most about 320 nm, at most about 330 nm, at most about 340 nm, at most about 350 nm, at most about 360 nm, at most about 370 nm, at most about 380 nm, at most about 390 nm, at most about 400 nm, at most about 410 nm, at most about 420 nm, at most about 430 nm, at most about 440 nm, at most about 450 nm, at most about 460 nm, at most about 470 nm, at most about 480 nm, at most about 490 nm, at most about 500 nm, at most about 510 nm, at most about 520 nm, at most about 530 nm, at most about 540 nm, at most about 550 nm, at most about 560 nm, at most about 570 nm, at most about 580 nm, at most about 590 nm, at most about 600 nm, at most about 610 nm, at most about 620 nm, at most about 630 nm, at most about 640 nm, at most about 650 nm, at most about 660 nm, at most about670 nm, at most about 680 nm, at most about 690 nm, at most about 700 nm, at most about 710 nm, at most about 720 nm, at most about 730 nm, at most about 740 nm, at most about 750 nm, at most about 760 nm, at most about 770 nm, at most about 780 nm, at most about 790 nm, at most about 800 nm, at most about 810 nm, at most about 820 nm, at most about 830 nm, at most about 840 nm, at most about 850 nm, or less. The wavelength of light may comprise a wavelength of about 200-850 nm, about 210-840 nm, about 220-830 nm, about 230-820 nm, about 240-810 nm, about 250-800 nm, about 260-790 nm, about 270-780 nm, about 280-770 nm, about 290-760 nm, about 300-750 nm, about 310-740 nm, about 320-730 nm, about 330-720 nm, about 340-710 nm, about 350-700 nm, about 360-690 nm, about 370-680 nm, about 380-670 nm, about 390-660 nm, about 400-650 nm, about 410-640 nm, about 420-630 nm, about 430-620 nm, about 440-610 nm, about 450-600 nm, about 460-590 nm, about 470-580 nm, about 480-570 nm, about 490-560 nm, about 500-550 nm, about 510-540 nm, or about 520-530 nm.

[0040] The one or more wavelengths of light of the stimulus may be applied for one or more durations of time. The one or more durations of time may comprise at least about 100 nanoseconds, at least about 1 microsecond, at least about 10 microseconds, at least about 100 microseconds, at least about 1 millisecond, at least about 10 milliseconds, at least about 100 milliseconds, at least about 1 second, at least about 10 seconds, at least about 100 seconds, at least about 1000 seconds, or more. The one or more durations of time may comprise at most about 100 nanoseconds, at most about 1 microsecond, at most about 10 microseconds, at most about 100 microseconds, at most about 1 millisecond, at most about 10 milliseconds, at most about 100 milliseconds, at most about 1 second, at most about 10 seconds, at most about 100 seconds, at most about 1000 seconds, or more.

[0041] The first state of one of the convertible residues (e.g. at least 10 convertible residues) may transition irreversibly into a second state. For example, the stimulus, may modify one of the at least 10 convertible residues and generate a chemical change to one of the at least 10 convertible residues such that the one of the at least 10 convertible residues cannot be modified again to return to the first state. The irreversible transition from the first state to the second state may be a permanent transition from the first state to the section state (e.g. the convertible residue cannot return to the first state after having transitioned to the second state). The irreversible transition from the first state of the at least 10 convertible residues into a second state of the at least 10 convertible residues may comprise one or more bond breakages, one or more changes in electronic structure, one or more electron transfer reactions, one or more interactions and / or complexations with other components, or a combination thereof. A non-limiting example of an irreversible transition is the reaction of a reactive oxygen species with one or more convertibleresidues (e.g. at least 10 convertible residues) comprising one or more fluorescent dyes causing a photobleaching reaction to the one or more fluorescent dyes. The photobleaching reaction to the one or more fluorescent dyes may comprise an irreversible transition from a fluorescent state (e.g. a first state) to a non-fluorescent state (e.g. a second state).

[0042] Another aspect of the disclosure provides a polymer. The polymer comprises a plurality of subunits, wherein: (a) a first subunit of the plurality of subunits comprises at least 10 convertible residues, wherein the at least 10 convertible residues: (i) are in a first state; (ii) are spaced evenly within the first subunit; and (iii) are configured to transition into a second state upon application of a stimulus; (b) a second subunit of the plurality of subunits does not comprise any convertible residues; and (c) each subunit of the plurality of subunits comprises at least 30 residues.

[0043] The polymers described herein may comprise one or more non-convertible residues. The one or more non-convertible residues do not change upon application of a specific stimulus. For example, the polymer may be exposed to a stimulus comprising a light, and the chemical structure of the one or more non-convertible residues does not change upon application of the stimulus. Other examples of stimuli that may be exposed to the one or more non-convertible residues include a temperature, a chemical stimulus, or a combination thereof. For clarity, the non-convertible residues are not prevented from being modified by any particular stimulus.

[0044] The one or more non-convertible residues may comprise a variety of types. For example, in some cases, the one or more non-convertible residues may comprise a nucleotide, an amino acid, a non-natural nucleotide, a non-natural amino acid, a linker, or a combination thereof. For example, in some cases, the one or more non-convertible residues may comprise one or more nucleotides. The one or more nucleotides of the one or more non-convertible residues may comprise one or more adenines (A), one or more cytosines (C), one or more guanines (G), one or more thymines (T), one or more uracils (U), or a combination thereof. The non-convertible residue may comprise a non-natural nucleotide, including one or more non-natural nucleotides comprising one or more alternatives to the phosphodiester backbone, and / or one or more substituents that may be placed onto a C-2 position of a nucleotide. For example, alternatives for the phorphodiester backbone may comprise a phosphorothioate backbone, a boranophosphate backbone, a phosphonate backbone, or a combination thereof. Substitients that may be placed on the C-2 position of a nucleotide may comprise fluorine (F), an amine (NH2), an O-methyl, or a combination thereof. Certain alternatives may be used for nucleotides. The one or more nonconvertible residues may comprise one or more formyl glycerol nucleic acids (FNA), one ormore glycol nucleic acids (GNA), one or more locked nucleic acids (LNA), one or more peptide nucleic acids (PNA), one or more xeno nucleic acids (XNA), or a combination thereof.

[0045] The one or more convertible residues of a subunit of the one or more subunits (e.g. the first subunit) of the polymers described herein may be separated by one or more non-convertible residues. In some cases, each of the convertible residues of a subunit of the one or more subunits (e.g. the first subunit) may be separated by the same number of non-convertible residues (e.g. the convertible residues of a subunit (e.g. the first subunit) may be evenly spaced). For example, a subunit may comprise at least 10 convertible residues, and each of the at least 10 convertible residues may be separated by 2 non-convertible residues. In some cases, each of the convertible residues of a subunit (e.g. the first subunit) may be separated by a variable number of nonconvertible residues. For example, a subunit may comprise at least 10 convertible residues, and one convertible residue of the at least 10 convertible residues may be separated by a second convertible residue by 2 non-convertible residues and a third convertible residue of the at least 10 convertible residues may be separated by a fourth convertible residue of the at least 10 convertible residues by 4 non-convertible residues. The convertible residues of a subunit of the one or more subunits (e.g. the first subunit) may be separated by at least 1, at least about 2, at least about 3, at least about 4, at least about 5, at least about 6, at least about 7, at least about 8, at least about 9, at least about 10, at least about 11, at least about 12, at least about 13, at least about 14, at least about 15, at least about 16, at least about 17, at least about 18, at least about 19, at least about 20, at least about 21, at least about 22, at least about 23, at least about 24, at least about 25, at least about 26, at least about 27, at least about 28, at least about 29, at least about 30, at least about 31, at least about 32, at least about 33, at least about 34, at least about 35, at least about 36, at least about 37, at least about 38, at least about 39, at least about 40, at least about 41, at least about 42, at least about 43, at least about 44, at least about 45, at least about 46, at least about 47, at least about 48, at least about 49, at least about 50, at least about 55, at least about 60, at least about 65, at least about 70, at least about 75, at least about 80, at least about 85, at least about 90, at least about 95, at least about 100, or more non-convertible residues. The convertible residues of a subunit (e.g. the first subunit) may be separated by at most 1, at most about 2, at most about 3, at most about 4, at most about 5, at most about 6, at most about 7, at most about 8, at most about 9, at most about 10, at most about 11, at most about 12, at most about 13, at most about 14, at most about 15, at most about 16, at most about 17, at most about 18, at most about 19, at most about 20, at most about 21, at most about 22, at most about 23, at most about 24, at most about 25, at most about 26, at most about 27, at most about 28, at most about 29, at most about 30, at most about 31, at most about 32, at most about 33, at most about 34, at most about35, at most about 36, at most about 37, at most about 38, at most about 39, at most about 40, at most about 41, at most about 42, at most about 43, at most about 44, at most about 45, at most about 46, at most about 47, at most about 48, at most about 49, at most about 50, at most about 55, at most about 60, at most about 65, at most about 70, at most about 75, at most about 80, at most about 85, at most about 90, at most about 95, at most about 100, or less non-convertible residues. The convertible residues of a subunit (e.g. the first subunit) may be separated by 1 to about 100, about 2 to about 95, about 3 to about 90, about 4 to about 85, about 5 to about 80, about 6 to about 75, about 7 to about 70, about 8 to about 65, about 9 to about 60, about 10 to about 55, about 11 to about 50, about 12 to about 49, about 13 to about 48, about 14 to about 47, about 15 to about 46, about 16 to about 45, about 17 to about 44, about 18 to about 43, about 19 to about 42, about 20 to about 41, about 21 to about 40, about 22 to about 39, about 23 to about 38, about 24 to about 37, about 25 to about 36, about 26 to about 35, about 27 to about 34, about 28 to about 33, about 29 to about 32, or about 30 to about 31 non-convertible residues. The convertible residues of a subunit (e.g. the first subunit) may be separated by about 5-20, about 10-100, or about 15-150 non-convertible residues. In some cases, entities other than one or more non-convertible residues may separate the one or more convertible residues of the one or more subunits.

[0046] Another aspect of the disclosure provides a polymer. The polymer comprises a plurality of subunits, wherein: (a) a first subunit of the plurality of subunits comprises at least 10 convertible residues, wherein each of the at least 10 convertible residues comprise a photo- modifiable group; (b) a second subunit of the plurality of subunits does not comprise any convertible residues; and (c) each subunit of the plurality of subunits comprises at least 30 residues.

[0047] In various aspects described herein, the polymer may comprise one or more subunits. The one or more subunits of the polymer (e.g. a plurality of subunits) may be connected by one or more linkers. For example, the one or more subunits may comprise nucleic acids and the one or more linkers may comprise one or more phosphodiester bonds, one or more polyethylene glycol groups, one or more methylene groups, one or more amide groups, one or more amine groups, one or more esters, one or more ethers, or a combination thereof. The one or more subunits may be connected to each other in an end to end fashion. For example, one end of one subunit may be connected to another end of another subunit.

[0048] The polymers described herein may comprise one or more nucleic acids, one or more polypeptides, one or more carbohydrates, one or more polyethylene glycols, one or morehydrocarbons, or a combination thereof. In some cases, the polymers described herein may comprise nucleic acid.

[0049] The one or more subunits of the polymer described herein may comprise one or more residues. The one or more residues of the one or more subunits of the polymer may comprise a variety of components including but not limited to one or more nucleotides, one or more amino acids, one or more non-natural amino acids, one or more non-natural amino acids, or a combination thereof. In some cases, a subunit of the one or more subunits of the polymer may comprise one type of residue (e.g. nucleotides). In some cases, a subunit of the one or more subunits may comprise more than one type of residue (e.g. nucleotides and amino acids). The one or more residues of the one or more subunits of the polymer may comprise one or more linkers connecting the one or more residues. In some cases, the one or more linkers may comprise one or more phosphodiester bonds, one or more polyethylene glycol groups, one or more methylene groups, one or more amide groups, one or more amine groups, one or more esters, one or more ethers, or a combination thereof. In some cases, the one or more residues of the one or more subunits of the polymer may be connected to each other directly without a linker.

[0050] The one or more residues of the one or more subunits of the polymer may comprise one or more nucleotides. The one or more nucleotides may comprise one or more Cs, one or more Ts, one or more Gs, one or more Us, One or more As, or a combination thereof. The one or more nucleotides of the one or more residues may comprise one or more modifications. The one or more modifications of the one or more residues may comprise one or more nucleic acid backbone modifications, one or more sugar modifications, or a combination thereof. The one or more backbone modifications of the one or more residues may comprise one or more phosphorothioates, one or more phosphorodithioates, one or more methylphosphonates, one or more phosphoramidates, one or more 2'-modifications, one or more bridged Rings, or a combination thereof. The one or more sugar modification of the one or more residues may comprise one or more 2’ fluorine modifications, on eor more 2’ O-methyl modifications, one or more locked nucleic acid modifications, one or more 2’ O-methoxy-ethyl modifications, or a combination thereof.

[0051] The one or more residues of the one or more subunits of the polymer may comprise one or more non-natural nucleotides. The one or more non-natural nucleotides of the one or more residues of the one or more subunits may comprise one or more non-natural nucleotides comprising one or more alternatives to the phosphodiester backbone, and / or one or more substituents that may be placed onto a C-2 position of a nucleotide. For example, alternatives forthe phorphodiester backbone may comprise a phosphorothioate backbone, a boranophosphate backbone, a phosphonate backbone, or a combination thereof. Substituents that may be placed on the C-2 position of a nucleotide may comprise fluorine (F), an amine (NH2), an O-methyl, or a combination thereof. Certain alternatives may be used for nucleotides. The one or more nonnatural nucleotides of the one or more residues of the one or more subunits may comprise one or more FNA, GNA, LNA, PNA, XNA, or a combination thereof.

[0052] The one or more residues of the one or more subunits of the polymer may comprise one or more amino acids. The one or more amino acids of the one or more residues of the one or more subunits may comprise one or more alanines, one or more aspartic acids, one or more asparagines, one or more arginines, one or more cytosines, one or more cysteines, one or more glycines, one or more glutamines, one or more histidines, one or more isoleucines, one or more leucines, one or more lysines, one or more methionines, one or more prolines, one or more phenylalanines, one or more serines, one or more tyrosines, one or more threonines, one or more tryptophans, one or more valines, or a combination thereof. The one or more amino acids of the one or more residues of the one or more subunits may comprise one or more non-natural amino acids. The one or more non-natural amino acids of the one or more residues of the one or more subunits may comprise one or more alloisoleucines, one or more allothreonines, one or more homocysteines, one or more homoserines, one or more isoserines, one or more isovalines, one or more methionines, one or more N-ethylalanines, one or more N-ethylglycines, one or more N- ethyl-P-alanines, one or more N-isopropylglycines, one or more N-methylalanines, one or more N-methyl-P-alanines, one or more norleucines, one or more norvalines, one or more N- propylglycines, one or more ornithines, one or more pipecolic acids, one or more sarcosines, one or more threonines, one or more t-leucines, one or more a,P-diaminopropionic acids, one or more a,y-diaminobutyric acids, one or more a-aminoisobutyric acids, one or more a-amino-n -butyric acids, one or more a-amino-n-heptanoic acids, one or more a-hydroxy-y-aminobutyric acids, one or more P-alanines, one or more P-aminoisobutyric acids, one or more P-amino-n-butyric acids, one or more y-aminobutyric acids, one or a combination thereof.

[0053] The polymers described herein may comprise a variety of types of subunits. For example, a subunit of the one or more subunits of the polymer may comprise one or more residues comprising nucleotides and be considered one type and another subunit of the one or more subunits of the polymer may comprise one or more residues comprising amino acids and be considered another type of subunits. In some cases, the type of subunit may refer to the type or residues within it, the combination of residues of a particular residue type (e.g. nucleotides), or a combination thereof. For example, one subunit of the one or more subunits may comprise a firstcombination of nucleotides and another subunit of the one or more subunits may comprise a second combination of nucleotides. The first and second combination of nucleotides may comprise some of the same nucleotides, some of the different nucleotides, or a combination thereof. For example, the first combination of nucleotides may comprise A, T, C, and G, whereas the second combination of nucleotides may comprise A, C, and G. In some cases, the first and / or second combination of nucleotides may comprise one or more non-natural nucleotides, one or more modifications, or a combination thereof. The polymers described herein may comprise at least about 1, at least about 2, at least about 3, at least about 4, at least about 5, at least about 6, at least about 7, at least about 8, at least about 9, at least about 10, at least about 11, at least about 12, at least about 13, at least about 14, at least about 15, at least about 16, at least about 17, at least about 18, at least about 19, at least about 20, at least about 21, at least about 22, at least about 23, at least about 24, at least about 25, at least about 26, at least about 27, at least about 28, at least about 29, at least about 30, at least about 31, at least about 32, at least about 33, at least about 34, at least about 35, at least about 36, at least about 37, at least about 38, at least about 39, at least about 40, at least about 41, at least about 42, at least about 43, at least about 44, at least about 45, at least about 46, at least about 47, at least about 48, at least about 49, at least about 50, at least about 55, at least about 60, at least about 65, at least about 70, at least about 75, at least about 80, at least about 85, at least about 90, at least about 95, at least about 100, at least about 125, at least about 150, at least about 175, at least about 200, at least about 300, at least about 400, at least about 500, or more types of subunits. The polymers described herein may comprise at most about 1, at most about 2, at most about 3, at most about 4, at most about 5, at most about 6, at most about 7, at most about 8, at most about 9, at most about 10, at most about 11, at most about 12, at most about 13, at most about 14, at most about 15, at most about 16, at most about 17, at most about 18, at most about 19, at most about 20, at most about 21, at most about 22, at most about 23, at most about 24, at most about 25, at most about 26, at most about 27, at most about 28, at most about 29, at most about 30, at most about 31, at most about 32, at most about 33, at most about 34, at most about 35, at most about 36, at most about 37, at most about 38, at most about 39, at most about 40, at most about 41, at most about 42, at most about 43, at most about 44, at most about 45, at most about 46, at most about 47, at most about 48, at most about 49, at most about 50, at most about 55, at most about 60, at most about 65, at most about 70, at most about 75, at most about 80, at most about 85, at most about 90, at most about 95, at most about 100, at most about 125, at most about 150, at most about 175, at most about 200, at most about 300, at most about 400, at most about 500, or less types of subunits. The polymers described herein may comprise about 1-500, about 2-400, about 3-300, about 4-200, about 5-175, about 6-150, about 7-125, about 8-100, about 9-95, about 10-90, about 11-85, about 12-80, about 13-75, about 14-70, about 15-65, about 16-60, about 17-55, about 18-50, about 19-49, about 20-48, about 21-47, about 22-46, about 23-45, about 24-44, about 25-43, about 26-42, about 27-41, about 28-40, about 29-39, about 30-38, about 31-37, about 32-36, or about 33-35 types of subunits. In some cases, the polymers described herein may comprise about 2-10, about 5-50, or about 10-100 types of subunits.

[0054] In some cases, the different types of subunits may be present the same number of times within a polymer, different number of times within a polymer or a combination thereof. For example, a polymer may comprise 4 types of subunits and the first type of subunit may be present 10 times, the second type of subunit may be present 10 times, the third type of subunit may be present 50 times and the fourth type of subunit may be present 63 times. The polymers described herein may comprise one or more types of subunits and the one or more types of subunits may be distributed within the polymer in a variety of ways. In some cases, the one or more types of subunits may be distributed in a random order (e.g. the one or more types of subunits may be distributed without a repeating pattern). In some cases, the one or more types of subunits may be distributed in a pattern. For example, in some cases, two types of subunits may be present within a polymer and the first type of subunit may precede and follow each instance of the second type of subunit. In some cases, a polymer may comprise two types of subunits, e.g. a first type and a second type. In some cases, the first type of subunit (e.g. the first subunit) may comprise one or more convertible residues (e.g. at least 10 convertible residues. In some cases, the second type of subunit (e.g. the second subunit) may not comprise any convertible residues. The polymer may comprise multiple copies of the first type of subunit (e.g. the first subunit) and multiple copies of the second type of subunit (e.g. the second subunit). In some cases, one or more copies of the first type of subunit (e.g. the first subunit) may be separated by at least one copy of the second type of subunit (e.g. the second subunit). In some cases, each copy of the first type of subunit (e.g. the first subunit) may be separated by at least one copy of the second type of subunit (e.g. the second subunit). In some cases, one or more copies of the second type of subunit (e.g. the second subunit) may be separated by at least one copy of the first type of subunit (e.g. the first subunit. In some cases, each copy of the second type of subunit (e.g. the second subunit) may be separated by at least one copy of the first type of subunit (e.g. the first subunit).

[0055] The polymer may comprise at least about 1, at least about 2, at least about 3, at least about 4, at least about 5, at least about 6, at least about 7, at least about 8, at least about 9, at least about 10, at least about 15, at least about 20, at least about 25, at least about 30, at least about 35,at least about 40, at least about 45, at least about 50, at least about 55, at least about 60, at least about 65, at least about 70, at least about 75, at least about 80, at least about 85, at least about 90, at least about 95, at least about 100, at least about 110, at least about 120, at least about 130, at least about 140, at least about 150, at least about 160, at least about 170, at least about 180, at least about 190, at least about 200, at least about 210, at least about 220, at least about 230, at least about 240, at least about 250, at least about 260, at least about 270, at least about 280, at least about 290, at least about 300, at least about 350, at least about 400, at least about 450, at least about 500, at least about 550, at least about 600, at least about 650, at least about 700, at least about 750, at least about 800, at least about 850, at least about 900, at least about 950, at least about 1000, at least about 1100, at least about 1200, at least about 1300, at least about 1400, at least about 1500, at least about 1600, at least about 1700, at least about 1800, at least about 1900, at least about 2000, at least about 2500, at least about 3000, at least about 3500, at least about 4000, at least about 4500, at least about 5000, at least about 5500, at least about 6000, at least about 6500, at least about 7000, at least about 7500, at least about 8000, at least about 8500, at least about 9000, at least about 9500, at least about 10000, or more copies of the first type of subunit (e.g. the first subunit). The polymer may comprise at most about 1, at most about 2, at most about 3, at most about 4, at most about 5, at most about 6, at most about 7, at most about 8, at most about 9, at most about 10, at most about 15, at most about 20, at most about 25, at most about 30, at most about 35, at most about 40, at most about 45, at most about 50, at most about 55, at most about 60, at most about 65, at most about 70, at most about 75, at most about 80, at most about 85, at most about 90, at most about 95, at most about 100, at most about 110, at most about 120, at most about 130, at most about 140, at most about 150, at most about 160, at most about 170, at most about 180, at most about 190, at most about 200, at most about 210, at most about 220, at most about 230, at most about 240, at most about 250, at most about 260, at most about 270, at most about 280, at most about 290, at most about 300, at most about 350, at most about 400, at most about 450, at most about 500, at most about 550, at most about 600, at most about 650, at most about 700, at most about 750, at most about 800, at most about 850, at most about 900, at most about 950, at most about 1000, at most about 1100, at most about 1200, at most about 1300, at most about 1400, at most about 1500, at most about 1600, at most about 1700, at most about 1800, at most about 1900, at most about 2000, at most about 2500, at most about 3000, at most about 3500, at most about 4000, at most about 4500, at most about 5000, at most about 5500, at most about 6000, at most about 6500, at most about 7000, at most about 7500, at most about 8000, at most about 8500, at most about 9000, at most about 9500, at most about 10000, or less copies of the first type of subunit (e.g. the first subunit). The polymer maycomprise about 1-10000, about 2-9500, about 3-9000, about 4-8500, about 5-8000, about 6- 7500, about 7-7000, about 8-6500, about 9-6000, about 10-5500, about 15-5000, about 20-4500, about 25-4000, about 30-3500, about 35-3000, about 40-2500, about 45-2000, about 50-1900, about 55-1800, about 60-1700, about 65-1600, about 70-1500, about 75-1400, about 80-1300, about 85-1200, about 90-1100, about 95-1000, about 100-950, about 110-900, about 120-850, about 130-800, about 140-750, about 150-700, about 160-650, about 170-600, about 180-550, about 190-500, about 200-450, about 210-400, about 220-350, about 230-300, about 240-290, about 250-280, or about 260-270 copies of the first type of subunit (e.g. the first subunit). In some cases, the polymer may comprise about 10-50, about 25-100, about 50-250 copies of the first type of subunit (e.g. the first subunit).

[0056] The polymer may comprise at least about 1, at least about 2, at least about 3, at least about 4, at least about 5, at least about 6, at least about 7, at least about 8, at least about 9, at least about 10, at least about 15, at least about 20, at least about 25, at least about 30, at least about 35, at least about 40, at least about 45, at least about 50, at least about 55, at least about 60, at least about 65, at least about 70, at least about 75, at least about 80, at least about 85, at least about 90, at least about 95, at least about 100, at least about 110, at least about 120, at least about 130, at least about 140, at least about 150, at least about 160, at least about 170, at least about 180, at least about 190, at least about 200, at least about 210, at least about 220, at least about 230, at least about 240, at least about 250, at least about 260, at least about 270, at least about 280, at least about 290, at least about 300, at least about 350, at least about 400, at least about 450, at least about 500, at least about 550, at least about 600, at least about 650, at least about 700, at least about 750, at least about 800, at least about 850, at least about 900, at least about 950, at least about 1000, at least about 1100, at least about 1200, at least about 1300, at least about 1400, at least about 1500, at least about 1600, at least about 1700, at least about 1800, at least about 1900, at least about 2000, at least about 2500, at least about 3000, at least about 3500, at least about 4000, at least about 4500, at least about 5000, at least about 5500, at least about 6000, at least about 6500, at least about 7000, at least about 7500, at least about 8000, at least about 8500, at least about 9000, at least about 9500, at least about 10000, or more copies of the second type of subunit (e.g. the second subunit). The polymer may comprise at most about 1, at most about 2, at most about 3, at most about 4, at most about 5, at most about 6, at most about 7, at most about 8, at most about 9, at most about 10, at most about 15, at most about 20, at most about 25, at most about 30, at most about 35, at most about 40, at most about 45, at most about 50, at most about 55, at most about 60, at most about 65, at most about 70, at most about 75, at most about 80, at most about 85, at most about 90, at most about 95, at most about 100, at most about 110, atmost about 120, at most about 130, at most about 140, at most about 150, at most about 160, at most about 170, at most about 180, at most about 190, at most about 200, at most about 210, at most about 220, at most about 230, at most about 240, at most about 250, at most about 260, at most about 270, at most about 280, at most about 290, at most about 300, at most about 350, at most about 400, at most about 450, at most about 500, at most about 550, at most about 600, at most about 650, at most about 700, at most about 750, at most about 800, at most about 850, at most about 900, at most about 950, at most about 1000, at most about 1100, at most about 1200, at most about 1300, at most about 1400, at most about 1500, at most about 1600, at most about 1700, at most about 1800, at most about 1900, at most about 2000, at most about 2500, at most about 3000, at most about 3500, at most about 4000, at most about 4500, at most about 5000, at most about 5500, at most about 6000, at most about 6500, at most about 7000, at most about 7500, at most about 8000, at most about 8500, at most about 9000, at most about 9500, at most about 10000, or less copies of the second type of subunit (e.g. the second subunit). The polymer may comprise about 1-10000, about 2-9500, about 3-9000, about 4-8500, about 5-8000, about 6- 7500, about 7-7000, about 8-6500, about 9-6000, about 10-5500, about 15-5000, about 20-4500, about 25-4000, about 30-3500, about 35-3000, about 40-2500, about 45-2000, about 50-1900, about 55-1800, about 60-1700, about 65-1600, about 70-1500, about 75-1400, about 80-1300, about 85-1200, about 90-1100, about 95-1000, about 100-950, about 110-900, about 120-850, about 130-800, about 140-750, about 150-700, about 160-650, about 170-600, about 180-550, about 190-500, about 200-450, about 210-400, about 220-350, about 230-300, about 240-290, about 250-280, or about 260-270 copies of the second type of subunit (e.g. the second subunit). In some cases, the polymer may comprise about 10-50, about 25-100, about 50-250 copies of the second type of subunit (e.g. the second subunit).

[0057] The polymers described herein may comprise at least about 1, at least about 2, at least about 3, at least about 4, at least about 5, at least about 6, at least about 7, at least about 8, at least about 9, at least about 10, at least about 15, at least about 20, at least about 25, at least about 30, at least about 35, at least about 40, at least about 45, at least about 50, at least about 55, at least about 60, at least about 65, at least about 70, at least about 75, at least about 80, at least about 85, at least about 90, at least about 95, at least about 100, at least about 110, at least about 120, at least about 130, at least about 140, at least about 150, at least about 160, at least about 170, at least about 180, at least about 190, at least about 200, at least about 210, at least about 220, at least about 230, at least about 240, at least about 250, at least about 260, at least about 270, at least about 280, at least about 290, at least about 300, at least about 350, at least about 400, at least about 450, at least about 500, at least about 550, at least about 600, at least about 650, atleast about 700, at least about 750, at least about 800, at least about 850, at least about 900, at least about 950, at least about 1000, at least about 1100, at least about 1200, at least about 1300, at least about 1400, at least about 1500, at least about 1600, at least about 1700, at least about 1800, at least about 1900, at least about 2000, at least about 2500, at least about 3000, at least about 3500, at least about 4000, at least about 4500, at least about 5000, at least about 5500, at least about 6000, at least about 6500, at least about 7000, at least about 7500, at least about 8000, at least about 8500, at least about 9000, at least about 9500, at least about 10000, or more subunits. The polymers described herein may comprise at most about 1, at most about 2, at most about 3, at most about 4, at most about 5, at most about 6, at most about 7, at most about 8, at most about 9, at most about 10, at most about 15, at most about 20, at most about 25, at most about 30, at most about 35, at most about 40, at most about 45, at most about 50, at most about 55, at most about 60, at most about 65, at most about 70, at most about 75, at most about 80, at most about 85, at most about 90, at most about 95, at most about 100, at most about 110, at most about 120, at most about 130, at most about 140, at most about 150, at most about 160, at most about 170, at most about 180, at most about 190, at most about 200, at most about 210, at most about 220, at most about 230, at most about 240, at most about 250, at most about 260, at most about 270, at most about 280, at most about 290, at most about 300, at most about 350, at most about 400, at most about 450, at most about 500, at most about 550, at most about 600, at most about 650, at most about 700, at most about 750, at most about 800, at most about 850, at most about 900, at most about 950, at most about 1000, at most about 1100, at most about 1200, at most about 1300, at most about 1400, at most about 1500, at most about 1600, at most about 1700, at most about 1800, at most about 1900, at most about 2000, at most about 2500, at most about 3000, at most about 3500, at most about 4000, at most about 4500, at most about 5000, at most about 5500, at most about 6000, at most about 6500, at most about 7000, at most about 7500, at most about 8000, at most about 8500, at most about 9000, at most about 9500, at most about 10000, or less subunits. The polymers described herein may comprise about 1-10000, about 2-9500, about 3-9000, about 4-8500, about 5-8000, about 6-7500, about 7-7000, about 8- 6500, about 9-6000, about 10-5500, about 15-5000, about 20-4500, about 25-4000, about 30- 3500, about 35-3000, about 40-2500, about 45-2000, about 50-1900, about 55-1800, about 60-1700, about 65-1600, about 70-1500, about 75-1400, about 80-1300, about 85-1200, about 90-1100, about 95-1000, about 100-950, about 110-900, about 120-850, about 130-800, about 140-750, about 150-700, about 160-650, about 170-600, about 180-550, about 190-500, about 200- 450, about 210-400, about 220-350, about 230-300, about 240-290, about 250-280, or about 260-270 subunits. The polymers described herein may comprise about 10-100, about 50-250, or about 100-1000 subunits.

[0058] The polymers described herein may comprise at least about 100, at least about 200, at least about 300, at least about 400, at least about 500, at least about 600, at least about 700, at least about 800, at least about 900, at least about 1,000, at least about 1,500, at least about 2,000, at least about 2,500, at least about 3,000, at least about 3,500, at least about 4,000, at least about4.500, at least about 5,000, at least about 5,500, at least about 6,000, at least about 6,500, at least about 7,000, at least about 7,500, at least about 8,000, at least about 8,500, at least about 9,000, at least about 9,500, at least about 10,000, at least about 20,000, at least about 30,000, at least about 40,000, at least about 50,000, at least about 60,000, at least about 70,000, at least about 80,000, at least about 90,000, at least about 100,000, at least about 200,000, at least about 300,000, at least about 400,000, at least about 500,000, at least about 600,000, at least about 700,000, at least about 800,000, at least about 900,000, at least about 1,000,000, or more residues. The polymers described herein may comprise at most about 100, at most about 200, at most about 300, at most about 400, at most about 500, at most about 600, at most about 700, at most about 800, at most about 900, at most about 1,000, at most about 1,500, at most about 2,000, at most about 2,500, at most about 3,000, at most about 3,500, at most about 4,000, at most about 4,500, at most about 5,000, at most about 5,500, at most about 6,000, at most about6.500, at most about 7,000, at most about 7,500, at most about 8,000, at most about 8,500, at most about 9,000, at most about 9,500, at most about 10,000, at most about 20,000, at most about 30,000, at most about 40,000, at most about 50,000, at most about 60,000, at most about 70,000, at most about 80,000, at most about 90,000, at most about 100,000, at most about 200,000, at most about 300,000, at most about 400,000, at most about 500,000, at most about 600,000, at most about 700,000, at most about 800,000, at most about 900,000, at most about 1,000,000, or fewer residues. The polymers described herein may comprise about 100-1000000, about 200- 900000, about 300-800000, about 400-700000, about 500-600000, about 600-500000, about 700-400000, about 800-300000, about 900-200000, about 1000-100000, about 1500-90000, about 2000-80000, about 2500-70000, about 3000-60000, about 3500-50000, about 4000-40000, about 4500-30000, about 5000-20000, about 5500-10000, about 6000-9500, about 6500-9000, about 7000-8500, or about 7500-8000 residues. The polymers described herein may comprise about 1,000-10,000, about 5,000-50,000, or a bout 10,000-100,000 residues.

[0059] A subunit of the one or more subunits described herein may comprise at least about 1, at least about 2, at least about 3, at least about 4, at least about 5, at least about 6, at least about 7, at least about 8, at least about 9, at least about 10, at least about 11, at least about 12, at least about13, at least about 14, at least about 15, at least about 16, at least about 17, at least about 18, at least about 19, at least about 20, at least about 21, at least about 22, at least about 23, at least about 24, at least about 25, at least about 26, at least about 27, at least about 28, at least about 29, at least about 30, at least about 31, at least about 32, at least about 33, at least about 34, at least about 35, at least about 36, at least about 37, at least about 38, at least about 39, at least about 40, at least about 41, at least about 42, at least about 43, at least about 44, at least about 45, at least about 46, at least about 47, at least about 48, at least about 49, at least about 50, at least about 55, at least about 60, at least about 65, at least about 70, at least about 75, at least about 80, at least about 85, at least about 90, at least about 95, at least about 100, at least about 125, at least about 150, at least about 175, at least about 200, at least about 300, at least about 400, at least about 500, at least about 600, at least about 700, at least about 800, at least about 900, at least about 1000, or more residues. A subunit of the one or more subunits described herein may comprise at most about 1, at most about 2, at most about 3, at most about 4, at most about 5, at most about 6, at most about 7, at most about 8, at most about 9, at most about 10, at most about 11, at most about 12, at most about 13, at most about 14, at most about 15, at most about 16, at most about 17, at most about 18, at most about 19, at most about 20, at most about 21, at most about 22, at most about 23, at most about 24, at most about 25, at most about 26, at most about 27, at most about 28, at most about 29, at most about 30, at most about 31, at most about 32, at most about 33, at most about 34, at most about 35, at most about 36, at most about 37, at most about 38, at most about 39, at most about 40, at most about 41, at most about 42, at most about 43, at most about 44, at most about 45, at most about 46, at most about 47, at most about 48, at most about 49, at most about 50, at most about 55, at most about 60, at most about 65, at most about 70, at most about 75, at most about 80, at most about 85, at most about 90, at most about 95, at most about 100, at most about 125, at most about 150, at most about 175, at most about 200, at most about 300, at most about 400, at most about 500, at most about 600, at most about 700, at most about 800, at most about 900, at most about 1000, or less residues. A subunit of the one or more subunits described herein may comprise about 1-1000, about 2-900, about 3-800, about 4-700, about 5-600, about 6-500, about 7-400, about 8-300, about 9-200, about 10-175, about 11-150, about 12-125, about 13-100, about 14-95, about 15-90, about 16-85, about 17-80, about 18-75, about 19-70, about 20-65, about 21-60, about 22-55, about 23-50, about 24-49, about 25-48, about 26-47, about 27-46, about 28-45, about 29-44, about 30-43, about 31-42, about 32-41, about 33-40, about 34-39, about 35-38, or about 36-37 residues. A subunit of the one or more subunits may comprise about 10-100, about 100-1,000, or about 500-5,000 residues.

[0060] In some cases, one or more subunit (e.g. the first subunit) may comprise one or more nucleotides. The one or more nucleotides of the one or more subunits (e.g. the first subunit) may comprise at least about 30 nucleotides, at least about 60 nucleotides, at least about 100 nucleotides, at least about 200 nucleotides, at least about 500 nucleotides, at least about 1000 nucleotides, or more. The one or more nucleotides of the one or more subunits (e.g. the first subunit) may comprise at most about 30 nucleotides, at most about 60 nucleotides, at most about 100 nucleotides, at most about 200 nucleotides, at most about 500 nucleotides, at most about 1000 nucleotides, or less.

[0061] In some cases, one or more subunit (e.g. the second subunit) may comprise one or more nucleotides. The one or more nucleotides of the one or more subunits (e.g. the second subunit) may comprise at least about 30 nucleotides, at least about 60 nucleotides, at least about 100 nucleotides, at least about 200 nucleotides, at least about 500 nucleotides, at least about 1000 nucleotides, or more. The one or more nucleotides of the one or more subunits (e.g. the second subunit) may comprise at most about 30 nucleotides, at most about 60 nucleotides, at most about 100 nucleotides, at most about 200 nucleotides, at most about 500 nucleotides, at most about 1000 nucleotides, or less.

[0062] The polymers described herein may comprise one or more subunits (e.g. a first subunit) comprising one or more convertible residues. The one or more convertible residues of the one or more subunits (e.g. a first subunit) may be in a first state. The one or more convertible residues of the one or more subunits may be in a first state and be configured to transition into a second state. The second state of the one or more convertible residues may be transitioned to upon application of a stimulus.

[0063] The one or more convertible residues of the one or more subunits of the polymers described herein may comprise one or more nucleotides, one or more amino acids, one or more linkers, or a combination thereof. The one or more nucleotides of the one or more convertible residues may comprise one or more T, one or more C, one or more G, one or more U, one or more A, or a combination thereof. The one or more convertible residues may comprise a T. The One or more amino acids of the one or more convertible residues may comprise comprise one or more alanines, one or more aspartic acids, one or more asparagines, one or more arginines, one or more cytosines, one or more cysteines, one or more glycines, one or more glutamines, one or more histidines, one or more isoleucines, one or more leucines, one or more lysines, one or more methionines, one or more prolines, one or more phenylalanines, one or more serines, one or more tyrosines, one or more threonines, one or more tryptophans, one or more valines, or a combination thereof. The one or more amino acids of the one or more residues of the one ormore subunits may comprise one or more non-natural amino acids. The one or more non-natural amino acids of the one or more residues of the one or more subunits may comprise one or more alloisoleucines, one or more allothreonines, one or more homocysteines, one or more homoserines, one or more isoserines, one or more isovalines, one or more methionines, one or more N-ethylalanines, one or more N-ethylglycines, one or more N-ethyl-P-alanines, one or more N-isopropylglycines, one or more N-methylalanines, one or more N-methyl-P-alanines, one or more norleucines, one or more norvalines, one or more N-propylglycines, one or more ornithines, one or more pipecolic acids, one or more sarcosines, one or more threonines, one or more t-leucines, one or more a,P-diaminopropionic acids, one or more a,y-diaminobutyric acids, one or more a-aminoisobutyric acids, one or more a-amino-n-butyric acids, one or more a- amino-n-heptanoic acids, one or more a-hydroxy-y-aminobutyric acids, one or more P-alanines, one or more P-aminoisobutyric acids, one or more P-amino-n-butyric acids, one or more y- aminobutyric acids, one or a combination thereof.

[0064] The one or more convertible residues of the one or more subunits may comprise one or more linkers. In some cases, the one or more linkers may comprise one or more phosphodi esters, one or more polyethylene glycols, one or more methylenes, one or more ethylenes, one or more thioethers, one or more amides, one or more amines, one or more esters, one or more ethers, one or more triazole rings (e.g. a 1,2, 3, -triazole ring), one or more azides, one or more alkynes, or a combination thereof. The one or more convertible residues may comprise one or more modifications. The one or more modifications may comprise one or more dye modifications (e.g. one or more photo-modifiable groups). The one or more dye modifications (e.g. one or more photo-modifiable groups) of the one or more convertible residues may comprise indolium based cyanine dyes, benzo-indolium based cyanine dyes, pyridium based cyanine dyes, thiozolium based cyanine dyes, quinolinium based cyanine dyes, imidazolium based cyanine dyes, lanthanide chelates, Europium chelates, Terbium chelates, Alexa Fluor dyes, DyLight dyes, Atto dyes, LightCycler Red dyes, CAL Flour dyes, Oregon Green dyes, WellRED dyes, IRD dyes, and phycobilin dyes, DEG dyes, fluorescein derivatives, rhodamine derivatives, or a combination thereof. The one or more dye modifications (e.g. one or more photo-modifiable groups) of the one or more convertible residues may comprise TEX 615, TYE™ 665, TYE 705, SUN, ATTO™ 425, ATTO™ 488, ATTO™ 532, ATTO™ 550, ATTO™ 565, ATTO™ RholOl , ATTO™ 590, ATTO™ 633, ATTO™ 647, ATTO™ 700, Alexa Fluor® 488 (NHS Ester), Alexa Fluor® 532 (NHS Ester), Alexa Fluor® 546 (NHS Ester), Alexa Fluor® 594 (NHS Ester), Alexa Fluor® 647 (NHS Ester), Alexa Fluor® 660 (NHS Ester), Alexa Fluor® 750 (NHS Ester), IRDye® 700, IRDye® 800, Rhodamine Red™, 5-TAMRA™, Texas Red®-X, Lightcycler® 640 , Dy 750,Cy3, Cy5, Cy7, Cy5.5, AMCA, AMCA-NHS, AMCA-sulfo-NHS, AMCA-HPDP, DCIA, AMCE-hydrazide, BODIPY and derivatives such as BODIPY FL C3-SE, BODIPY 530 / 550 C3, BODIPY 530 / 550 C3-SE, BODIPY 530 / 550 C3 hydrazide, BODIPY 493 / 503 C3 hydrazide, BODIPY FL C3 hydrazide, BODIPY FL IA, BODIPY 530 / 551 IA, Br-BODIPY 493 / 503, Cascade Blue and derivatives, TRITC, TMR, lissamine rhodamine, AlexaFluor Texas Red, rhodamine B, rhodamine 6G, rhodamine 10, TMR-iodoacetamide, lissamine rhodamine B sulfonyl chloride, lissamine rhodamine B sulfonyl hydrazine, Texas Red sulfonyl chloride, Texas Red hydrazide, coumarin and coumarin, Cascade Blue acetyl azide, Cascade Blue cadaverine, Cascade Blue ethylenediamine, Cascade Blue hydrazide, Lucifer Yellow, Lucifer Yellow CH, BCPDA, TBP, TMT, BHHCT, BCOT, Malachite green, stilbene, carboxyfluorescein, tetrachlorofluorescein, hexachlorofluorescein, carboxynapthofluorescein, fluorescein isothiocyanate, NHS-fluorescein, iodoacetamidofluorescein, fluorescein maleimide, SAMSA- fluorescein, fluorescein thiosemicarbazide, phycoerythrin, carbohydrazinomethylthioacetyl- amino fluorescein, rhodamine, JOE, or a combination thereof. In some cases, the one or more convertible residues may comprise a dye modification connected to a nucleotide (e.g. a T) via a linker.

[0065] A subunit of the one or more subunits (e.g. the first subunit) may comprise a variable number of convertible residues. In some cases, each of the subunits of the one or more subunits of a polymer described herein may comprise the same number of convertible residues. For example, each of the subunits within a polymer may comprise 10 convertible residues. In some cases, each of the subunits of the one or more subunits of a polymer described herein may comprise a different number of convertible residues. For example, a polymer may comprise 10 subunits, and each subunit of the 10 subunits comprises a different number of convertible residues. In some cases, a first subset of subunits of the one or more subunits may comprise a first number of convertible residues and a second subset of subunits of the one or more subunits may comprise a second number of convertible residues. The first number of convertible residues of the first subset of subunits may be 10 convertible residues and the second number of convertible residues of the second subset of subunits may be 0 convertible residues. In some cases, the convertible residues of a subunit of the one or more subunits may all be the same. For example, the convertible residues of a subunit of the one or more subunits may all comprise a Cy5 dye modification. In some cases, one or more convertible residues of a subunit of the one or more subunits may be different. For example, a first subset of convertible residues of a subunit of the one or more subunits may comprise a Cy5 dye modification and a second subset ofconvertible residues of the subunit of the one or more subunits may comprise an Lucifer Yellow dye modification.

[0066] A subunit of the one or more subunits (e.g. the first subunit) may comprise at least about 1, at least about 1, at least about 2, at least about 3, at least about 4, at least about 5, at least about 6, at least about 7, at least about 8, at least about 9, at least about 10, at least about 11, at least about 12, at least about 13, at least about 14, at least about 15, at least about 16, at least about 17, at least about 18, at least about 19, at least about 20, at least about 21, at least about 22, at least about 23, at least about 24, at least about 25, at least about 26, at least about 27, at least about 28, at least about 29, at least about 30, at least about 31, at least about 32, at least about 33, at least about 34, at least about 35, at least about 36, at least about 37, at least about 38, at least about 39, at least about 40, at least about 41, at least about 42, at least about 43, at least about 44, at least about 45, at least about 46, at least about 47, at least about 48, at least about 49, at least about 50, at least about 55, at least about 60, at least about 65, at least about 70, at least about 75, at least about 80, at least about 85, at least about 90, at least about 95, at least about 100, at least about 125, at least about 150, at least about 175, at least about 200, at least about 300, at least about 400, at least about 500, at least about 600, at least about 700, at least about 800, at least about 900, at least about 1000, or more convertible residues. A subunit of the one or more subunits (e.g. the first subunit) may comprise at most about 1, at most about 1, at most about 2, at most about 3, at most about 4, at most about 5, at most about 6, at most about 7, at most about 8, at most about 9, at most about 10, at most about 11, at most about 12, at most about 13, at most about 14, at most about 15, at most about 16, at most about 17, at most about 18, at most about 19, at most about 20, at most about 21, at most about 22, at most about 23, at most about 24, at most about 25, at most about 26, at most about 27, at most about 28, at most about 29, at most about 30, at most about 31, at most about 32, at most about 33, at most about 34, at most about 35, at most about 36, at most about 37, at most about 38, at most about 39, at most about 40, at most about 41, at most about 42, at most about 43, at most about 44, at most about 45, at most about 46, at most about 47, at most about 48, at most about 49, at most about 50, at most about 55, at most about 60, at most about 65, at most about 70, at most about 75, at most about 80, at most about 85, at most about 90, at most about 95, at most about 100, at most about 125, at most about 150, at most about 175, at most about 200, at most about 300, at most about 400, at most about 500, at most about 600, at most about 700, at most about 800, at most about 900, at most about 1000, or less convertible residues. A subunit of the one or more subunits (e.g. the first subunit) may comprise about 1-1000, about 2-900, about 3-800, about 4-700, about 5-600, about 6-500, about 7-400, about 8-300, about 9-200, about 10-175, about 11-150, about 12-125, about13-100, about 14-95, about 15-90, about 16-85, about 17-80, about 18-75, about 19-70, about OOS, about 21-60, about 22-55, about 23-50, about 24-49, about 25-48, about 26-47, about 27-46, about 28-45, about 29-44, about 30-43, about 31-42, about 32-41, about 33-40, about 34-39, about 35-38, or about 36-37 convertible residues. A subunit of the one or more subunits may comprise about 5-25, about 10-50, or about 25-100 convertible residues.

[0067] A subunit of the one or more subunits may comprise one or more non-convertible residues. The one or more non-convertible residues of the subunit of the one or more subunits may comprise all of the same type of residues. For example, the one or more non-convertible residues of the one subunit of the one or more subunits may comprise nucleotides. In some cases, a subunit of the one or more subunits may comprise more than one type of non-convertible residue (e.g. a combination of nucleotides and amino acids.) A subunit of the one or more subunits may comprise at least about 1, at least about 2, at least about 3, at least about 4, at least about 5, at least about 6, at least about 7, at least about 8, at least about 9, at least about 10, at least about 20, at least about 30, at least about 40, at least about 50, at least about 60, at least about 70, at least about 80, at least about 90, at least about 100, at least about 110, at least about 120, at least about 130, at least about 140, at least about 150, at least about 160, at least about170, at least about 180, at least about 190, at least about 200, at least about 250, at least about300, at least about 450, at least about 500, at least about 550, at least about 600, at least about650, at least about 700, at least about 750, at least about 800, at least about 850, at least about900, at least about 950, at least about 1000, at least about 2000, at least about 3000, at least about 4000, at least about 5000, at least about 6000, at least about 7000, at least about 8000, at least about 9000, at least about 10000, or more non-convertible residues. A subunit of the one or more subunits may comprise at most about 1, at most about 2, at most about 3, at most about 4, at most about 5, at most about 6, at most about 7, at most about 8, at most about 9, at most about 10, at most about 20, at most about 30, at most about 40, at most about 50, at most about 60, at most about 70, at most about 80, at most about 90, at most about 100, at most about 110, at most about 120, at most about 130, at most about 140, at most about 150, at most about 160, at most about170, at most about 180, at most about 190, at most about 200, at most about 250, at most about300, at most about 450, at most about 500, at most about 550, at most about 600, at most about650, at most about 700, at most about 750, at most about 800, at most about 850, at most about900, at most about 950, at most about 1000, at most about 2000, at most about 3000, at most about 4000, at most about 5000, at most about 6000, at most about 7000, at most about 8000, at most about 9000, at most about 10000, or more non-convertible residues. A subunit of the one or more subunits may comprise about 1-10000, about 2-9000, about 3-8000, about 4-7000, about 5-6000, about 6-5000, about 7-4000, about 8-3000, about 9-2000, about 10-1000, about 20-950, about 30-900, about 40-850, about 50-800, about 60-750, about 70-700, about 80-650, about 90- 600, about 100-550, about 110-500, about 120-450, about 130-300, about 140-250, about 150- 200, about 160-190, or about 170-180 non-convertible residues. A subunit of the one or more subunits may comprise about 50-500, about 100-1,000, or about 500-5,000 non-convertible residues.

[0068] The polymers described herein may comprise a subset of subunits that may comprise one or more convertible residues (e.g. a first subunit) and a second subset of subunits that may not comprise one or more convertible residues (e.g. a second subunit). In some cases, the number of subunits that may comprise one or more convertible residues may be the same as the number of subunits that may not comprise one or more convertible residues within a polymer. In some cases, the number of subunits that may comprise one or more convertible residues may be greater than the number of subunits that may not comprise one or more convertible residues within a polymer. In some cases, the number of subunits that may comprise one or more convertible residues may be less than the number of subunits that may not comprise one or more convertible residues within a polymer. A subunit that may comprise one or more convertible residues may be separated by a subunit that may not comprise one or more convertible residues using a linker. In some cases, a subunit that may comprise one or more convertible residues may be distinguishable from a subunit that may not comprise one or more convertible residues by the presence and / or absence of the one or more convertible residues within the one or more subunits. In some cases, one or more subunits of the polymers described herein may lack a residue. For example, one or more subunits (e.g. the second subunit) may lack one of C, G, T, A, or U. In some cases, one or more subunits (e.g. the second subunit) may lack one or more of C, G, T, A, U, or a combination thereof. The one or more subunits that may lack one or more of C, G, T, A, U, or a combination thereof may also not comprise one or more convertible residues.

[0069] The polymers described herein may comprise a GC content. For example, the polymers described herein may comprise nucleic acid comprising C, G, A, and T, and the percentage of the nucleic acid comprising C and / or G may be the GC content. The GC content may be denoted as a percentage. A subunit of the one or more subunits may comprise a GC content, as described herein. A subunit of the one or more subunits (e.g. the first subunit), may comprise a GC content of at least about 10% GC, at least about 15% GC, at least about 20% GC, at least about 25% GC, at least about 30% GC, at least about 35% GC, at least about 40% GC, at least about 45% GC, at least about 50% GC, at least about 55% GC, at least about 60% GC, at least about 65% GC, at least about 70% GC, at least about 75% GC, at least about 80% GC, at least about 85% GC, atleast about 90% GC or more. A subunit of the one or more subunits (e.g. the first subunit), may comprise a GC content of at most about 10% GC, at most about 15% GC, at most about 20% GC, at most about 25% GC, at most about 30% GC, at most about 35% GC, at most about 40%GC, at most about 45% GC, at most about 50% GC, at most about 55% GC, at most about 60%GC, at most about 65% GC, at most about 70% GC, at most about 75% GC, at most about 80%GC, at most about 85% GC, at most about 90% GC or less. A subunit of the one or more subunits (e.g. the first subunit), may comprise a GC content of about 10-90% GC, about 15-85% GC, about 20-80% GC, about 25-75% GC, about 30-70% GC, about 35-65% GC, about 40-60% GC, or about 45-55% GC. A subunit of the one or more subunits (e.g. the second subunit), may comprise a GC content of at least about 10% GC, at least about 15% GC, at least about 20% GC, at least about 25% GC, at least about 30% GC, at least about 35% GC, at least about 40% GC, at least about 45% GC, at least about 50% GC, at least about 55% GC, at least about 60% GC, at least about 65% GC, at least about 70% GC, at least about 75% GC, at least about 80% GC, at least about 85% GC, at least about 90% GC or more. A subunit of the one or more subunits (e.g. the second subunit), may comprise a GC content of at most about 10% GC, at most about 15% GC, at most about 20% GC, at most about 25% GC, at most about 30% GC, at most about 35%GC, at most about 40% GC, at most about 45% GC, at most about 50% GC, at most about 55%GC, at most about 60% GC, at most about 65% GC, at most about 70% GC, at most about 75%GC, at most about 80% GC, at most about 85% GC, at most about 90% GC or less. A subunit of the one or more subunits (e.g. the second subunit), may comprise a GC content of about 10-90% GC, about 15-85% GC, about 20-80% GC, about 25-75% GC, about 30-70% GC, about 35-65% GC, about 40-60% GC, or about 45-55% GC.

[0070] The polymers described herein may comprise one or more cleavable sites. The one or more cleavable sites may be used for manufacturing and / or assembly of the polymers described herein. The one or more cleavable sites may be distributed within the polymer. For example, one or more cleavable sites may be present one or more ends of the polymer. In some cases, a cleavable site may be present in one or more types of subunits (e.g. the first subunit, and / or the second subunit). A cleavable site of the one or more cleavable sites may be a restriction stie. The one or more restriction sites may be cleavable by an enzyme. The enzyme may be an endonuclease, an exonuclease, or a combination thereof. In some cases the enzyme may comprise Aatll, Acc65I, AccI, Acil, Acll, Acul, Aflll, Agel-HF®, Agel-HF®, AhdI, Alul, AlwNI, Apal, ApaLI, ApeKI, ApoI-HF®, ApoI-HF®, Asci, Asel, Aval, Avail, Avril, BaeGI, Bael, BamHI, BamHI-HF®, BamHI-HF®, BbsI, BbsI-HF®, BbsI-HF®, Bbvl, BciVI, Bell, BclI-HF, BclI-HF, BcoDI, BfuAI, Bgll, Bglll, BlpI, BmgBI, BmtI-HF®, BmtI-HF®, Bpml,BpuEI, BsaAI, BsaHI, BsaI-HF®v2, BsaI-HF®v2, BsaWI, BsaXI, BseRI, Bsgl, BsiEI, BsiWI, BsiWI-HF®, BsiWI-HF®, BslI, BsmAI, BsmBI-v2, BsmI, BsoBI, Bspl286I, BspCNI, BspEI, BspHI, BspQI, BsrBI, BsrDI, BsrGI-HF®, BsrI, BssHII, BstBI, BstEII-HF®, BstEII-HF®, BstNI, BstUI, BstXI, BstYI, BstZ17I-HF®, BstZ17I-HF®, Bsu36I, Btgl, BtsCI, Cac8I, Clal, CspCI, CviQI, Ddel, Dpnl, Dpnl, DpnII, DpnII, Dral, Dralll-HF®, Dralll-HF®, DrdI, Eagl- HF®, Eagl-HF®, Earl, Eco53kl, EcoNI, EcoOl 091, EcoP15I, EcoRI, EcoRI-HF®, EcoRI-HF®, EcoRV, EcoRV-HF®, EcoRV-HF®, Esp3I, Fnu4HI, Fsel, FspI, Haelll, Hhal, Hindi, Hindlll- HF®, Hindlll-HF®, Hinfl, HinPlI, Hpall, Hpall, HphI, Hpyl66II, HpyAV, HpyCH4IV, HpyCH4V, I-Ceul, I-Scel, KpnI-HF®, KpnI-HF®, Mbol, Mfel-HF®, Mfel-HF®, MluCI, Mlul- HF®, Mlyl, Mmel, Mnll, Msel, MslI, MspAlI, MspI, MspI, MspJI, Mwol, Nb.BbvCI, Nb.BsmI, Nb.BsrDI, Nb.BssSI, Nb.BtsI, Neil, Ncol, NcoI-HF®, NcoI-HF®, Ndd, NgoMIV, Nhel-HF®, Nhel-HF®, Nlalll, Notl, Notl-HF®, Notl-HF®, NruI-HF®, Nsil, Nsil-HF®, NspI, Nt.AlwI, Nt.BbvCI, Nt.BsmAI, Nt.BspQI, Nt.BstNBI, Nt.CviPII, Pad, PaeR7I, PflFI, PflMI, PI-PspI, PI- Scel, Pmel, Pmll, PpuMI, PshAI, PstI, Pstl-HF®, Pstl-HF®, PvuI-HF®, PvuI-HF®, PvuII, PvuII-HF®, PvuII-HF®, Rsal, SacI-HF®, SacI-HF®, Sadi, Sall, Sall-HF®, Sall-HF®, SapI, Sbfl-HF®, Sbfl-HF®, Scal-HF®, Scal-HF®, Sfil, Sfol, Smal, Spel-HF®, Spel-HF®, Sphl- HF®, Sphl-HF®, SspI-HF®, SspI-HF®, Stul, StyD4I, Styl-HF®, Styl-HF®, Swal, Taql-v2, Tfil, Tsel, TspMI, TspRI, Tthl 1 II, Xbal, Xhol, Xmal, XmnI, or a combination thereof. The one or more restriction sites of the polymers described herein may be cleavable by a golden gate assembly nuclease.

[0071] Another aspect of the disclosure provides a method for processing a polymer. The method comprises: (a) providing a polymer comprising a plurality of subunits, wherein (i) a first subunit of the plurality of subunits comprises at least 10 convertible residues, wherein the at least 10 convertible residues are in a first state and transition irreversibly into a second state upon application of a stimulus; (ii) a second subunit of said plurality of subunits comprises nonconvertible residues and does not comprise any convertible residues, wherein said nonconvertible residues do not change upon application of a stimulus; and (iii) each subunit of said plurality of subunits comprises at least 30 residues; and (b) applying said stimulus to said first subunit of said plurality of subunits, thereby causing at least a portion of said at least 10 convertible residues to irreversibly transition into a second state.

[0072] Processing the polymers described herein may comprise modifying the polymers to convert one or more convertible residues of the polymers from a first state to a second state. Modifying the polymers to convert one or more convertible residues of the polymers from a first state to a second state may comprise applying a stimulus to the one or more convertible residues.Applying a stimulus to the one or more convertible residues may comprise locally applying a stimulus, globally applying a stimulus, or a combination thereof. For example, an example of locally applying a stimulus may comprise a polymer as described herein that may be subjected to a light at a specific location within the polymer corresponding to one subunit. The convertible residues within the subunit that may be subjected to light may be converted from a first state to a second state as a result of being subjected to the light. An example of globally applying a stimulus, may comprise subjecting the entire polymer to light.

[0073] Mechanisms to modify the polymers to convert one or more convertible residues of the polymers from a first state to a second state may comprise passing the polymer through a polymer writing system. The polymer writing system may comprise one or more fluidic nanochannels (e.g. one or more nanopores), one or more light sources, one or more computer processors, one or more actuators, one or more pumps, one or more membranes, or a combination thereof. The one or more fluidic nanochannels may enable a polymer as described herein to flow through. The one or more pumps and / or actuators may facilitate the polymers as described herein to flow through the nanochannels. The light source may be applied to a polymer as it flows through the nanochannels. The light source may comprise one or more light emitting diodes (LED). The light source may provide illumination at one or more wavelengths, including but not limited to about 375 nm, about 405 nm, about 488 nm, about 530 nm, about 570 nm, about 590 nm, about 635 nm, about 638 nm, about 700 nm or a combination thereof. The one or more computer processors may provide instructions for flowing the polymers through the nanochannels and / or emitting light from the one or more light sources. The polymer modified by the methods as described herein may include one or more of the compositions described herein.

[0074] Methods and systems that can efficiently and securely store data for extended terms (e.g., without the need for repetitive rewriting of data) with minimized susceptibility to cyber-attacks, hacks, data breaches, data losses, and data contamination are highly valuable. Most data is typically stored electronically as binary code, however electronically stored data may be susceptible to the aforementioned vulnerabilities. It has been proposed that DNA could serve as an efficient, secure, and long term means of storing information, however preexisting methods of writing data to DNA fail to provide practically useful speeds and cost, and volumes of data storage. For example, chemical or enzymatic approaches are slow, require assembly of DNA nucleotide by nucleotide, and require knowing the data which is to be “written” to the DNA at the time of DNA synthesis. The chemical or enzymatic approaches for constructing DNA of arbitrary sequence are also limited to short strands, typically 200 nucleotides or less, severely limiting data capacity. Even if it was commercially practicable to encode electronically storedinformation onto DNA (e.g., using nucleotide repetitive sequences), it may not easily be replicated or produced with existing reagents and methods, as recombination and laddering is observed to occur in PCR amplification when perfect repeats are present. There has not yet been disclosed a reliable and effective means of constructing or producing or replicating very long sequences of writable (or data encodable) DNA polymers with high fidelity; similarly, for prior approaches, once data is encoded in a nucleic acid sequence, the data then must be decoded by sequencing, which remains a time and resource intensive process, notwithstanding the development of many next-generation DNA sequencing techniques.

[0075] A DNA backbone with chemically modifiable moieties attached to one or more nucleobases may store data within the DNA in the modifiable moieties as opposed to a nucleotide sequence. The efficiency of writing and reading data stored on DNA can be significantly increased by storing the data in the chemically modifiable moieties attached to one or more nucleobases. Naturally occurring DNA sequences may not be uniformly labeled with a modifiable group with nearly even spacing along their length. An engineered sequence that is nearly repetitive may be required. However, perfectly repetitive DNA may be difficult to construct. For example, existing techniques such as rolling circle amplification produce long repeating single-stranded DNA but may lack the ability to control the length of the final DNA product or readily produce a homogeneous double stranded product. Similarly, recombination and laddering may be observed in PCR amplification, and for bacterial replication of repetitive sequences, polymerases have been observed to skip homopolymer tracks during DNA synthesis, all of which may prevent the replication of a known, iteratively repeated sequence of chemically modifiable moieties attached to a specific nucleotide across a very long DNA polymer with high fidelity, which can be used to store commercially practicable volumes of data on a writable DNA polymer, and permit for such data to be read using non-sequencing based methodology (e.g., purely optical techniques including fluorescent labeling).

[0076] Provided herein are molecule sequences that may be capable of encoding information and data (e.g., along their length), including DNA polymers. Such DNA polymers may comprise a known, iteratively repeated nucleotide / chemically modifiable moiety; may comprise the chemically modifiable moiety(s) in a known, iteratively repeated sequence or spacing by being attached to the known, iteratively repeated nucleotide; and can be replicated and / or attached to one another as to produce very long length DNA polymers comprising the chemically modifiable moieties in the known, iteratively repeated sequence or spacing across an extended DNA polymer (e.g., 7 kbp-200 kbp). Such molecules may comprise one or more subunits (e.g., a plurality of subunits) with certain characteristics, such that identities / properties of the moleculeor the subunits of the molecule correspond to pieces of information encoded by the molecules and subunits thereof.

[0077] The molecules described herein and compositions comprising such molecules can be used to store data efficiently and securely for intended durations of time, in some cases, for the long term, while minimizing various risks to the stored data. This may be accomplished by encoding / writing the data (information to be stored) in or using the molecules described herein, in some cases, a polymer comprising a plurality of monomers each comprising one or more sections, and in some cases, a nucleic acid molecule comprising a plurality of nucleotides or nucleobases. In some examples, encodable / writable molecules may be manufactured, provided, or obtained, prior to encoding / writing data into the molecule. Provided are also compositions comprising such molecules (e.g., writable molecules or encodable molecules), methods of assembling such molecules, compositions comprising such molecules, and methods of use thereof. In some cases, such molecules may comprise polymers. In some cases, such molecules may comprise nucleic acid molecules and / or polynucleotides. In some cases, such molecules are deoxynucleic acid (DNA) molecules. In some cases, the DNA molecules may be double stranded, and in some cases they may be single-stranded.

[0078] In some examples, the molecules, compositions, and methods may be capable of storing large sizes / volumes of data, for example, due to the long length of the writable DNA polymers and large number of modifiable groups which are disclosed and can be manufactured by using the methods and compositions disclosed herein. In some examples, data that can be stored using the molecules and compositions of the present disclosure comprise digital and / or electronic data, or data stored as binary code. In some examples, information may be written / encoded irreversibly onto the DNA polymers, for example, such that data is not lost, damaged, or deleted (unintentionally or maliciously). The molecules may be referred to as writable molecules, encodable molecules, writable DNA polymers, or encodable DNA polymers. In some cases, writable / encodable molecules or DNA polymers are manufactured using the methods provided herein. The writable molecules can then be used for encoding data after the manufacture of the molecules. In some embodiments, data encoding is not performed prior to synthesizing / manufacturing the molecule. In some embodiments, data may be written or encoded after synthesizing / manufacturing the DNA polymer. For example, the data may not be stored or encoded in the initial sequence of the nucleotides of the DNA polymer. The molecule can be manufactured (e.g., generically) without initially being linked to the data that is to be stored or without encoding the data. Instead, the writable molecules and compositions comprising such writable molecules can be provided in form of an article, substance, a solution, a transferrablemass, in some cases, in solid form, in some examples in form of tapes of writable molecules (e.g., writable DNA polymers or “DNA tapes”). The molecules can then be used to encode data (e.g., at any point in time, in some cases, after a period of time after the molecule has been manufactured).

[0079] In some examples, a polymer (writable / encodable molecule) of the present disclosure comprises a plurality of subunits. In some examples, one or more subunits of the plurality of subunits of the molecule are modifiable, such that the modifying the subunits encodes data into the subunit and generates a modified subunit, such that measuring a property of the modified subunit provides access to the piece of data (e.g., reading of the stored data). In some cases, the modified subunit but not the subunit (before modification) encodes the data. In some cases, the unmodified subunit indicates a first data state (e.g., a “0” in binary code) and the modified subunit indicates a second data state (e.g., a “1” in binary code). Such an embodiment of storing data as binary code in modified and unmodified states of the polymer subunits may benefit from the chemically modifiable moieties occurring about the length of the polymer in a known, iteratively repeated interval / sequence (thereby providing a known data resolution defined by a portion length of the polymer (e.g., length of polymer subunits) for writing data. This may facilitate the capability to manufacture, produce, provide, and / or obtain the molecule (writable molecule) even before the availability or generation of the data as a medium for data storage. This can further facilitate the capability to quickly write data by using locally impinged light to modify portions of the polymers submits as to comprise modified and unmodified subunits storing data in binary code, and the capability to quickly read data by measuring a fluorescent state of the subunits along the polymer and identifying the binary code based on the modified and unmodified state (e.g., fluorescent or bleached state) of the subunits.

[0080] Furthermore, in some cases, the generation of the molecule carrying the data (e.g., the modified molecule) may not be performed via chemical synthesis, via chemical ligation, via split-and-pool synthesis, solid phase synthesis, and / or with the aid of an enzyme. The molecules and methods of the present disclosure provide for convenient, fast, and efficient methods of data writing / encoding, storage, and reading / decoding which can be in many cases, less expensive, less labor intensive, and less time-consuming than chemical synthesis, chemical ligation, split- and-pool synthesis, and solid phase nucleic acid molecule synthesis for generating a molecule that encodes data.

[0081] For example, an alternative approach may be to link data to sequences of molecules (e.g., DNA) in a database, such that the sequences of DNA correspond to the information in the database. The DNA molecules can then be synthesized via chemical synthesis, via chemicalligation, via split-and-pool synthesis, and solid phase synthesis, or with the aid of an enzyme to store such data. Sequencing can be performed to provide access to the data as it corresponds to the sequence of the sequenced DNA. Such alternative method may in some cases be labor intensive, slow, and requires chemicals as part of the writing process. Provided herein are methods for generating writable molecules as media for data storage without the use of sequence itself to encode the data, and without the need to assemble the molecule while writing the data. Instead, the writable molecules are manufactured before data encoding. The writable molecules can be transferred, moved, shipped, and handled independently of the data and prior to data encoding. In some examples, application of a stimulus or making a modification to the writable molecule may allow for writing / encoding data into the writable molecule. This can be performed after the writable molecule has been manufactured. This method may be faster, more efficient, and less expensive than encoding data into the molecule by linking the data to the sequence of the original unmodified molecule and synthesizing the data-encoding molecule.

[0082] The molecules (e.g., writable / encodable molecules) of the present disclosure may be further used to make a composition comprising the molecule, such that the composition is configured for data storage. Provided herein are such molecules that are in some cases configured for or capable of data storage or being used as a medium for data storage. Provided are also compositions comprising such molecules, the methods of manufacture of such molecules, methods of making the compositions, and methods of use of the molecules and the compositions, such as for data storage and / or data retrieval.

[0083] In some examples, the stimulus applied to modify the molecule may comprise light exposure, and a modifiable nucleotide or modifiable molecule may comprise a chemically modifiable moiety which is photo-modifiable (configured to be modified upon exposure to a light, such as by transitioning from a fluorescent state to a non- fluorescent state, or vice-versa). In such embodiments, the method of use of the molecule may comprise exposing a monomer / nucleobase of the molecule (or a polymer subunit, or portion thereof) to light (in some cases at a specific wavelength), such that the light modifies the chemically modifiable moiety, thereby generating a modified nucleobase, and such that the modified nucleobase of the molecule contains information or pieces of data that are stored to be read (e.g., at some point in the future, for example, as binary code). In some embodiments, a group or cluster of modifiable moieties may be modified at a time, to encode a “bit” of binary code. The modifiable moieties of the molecule can be placed in designated locations on the molecule such that the modifications facilitated by the application of the stimulus (light exposure) contain / encode the data and the data are accessible upon measuring a property of the modified molecule. In some embodiments, thestimulus is applied with a predetermined pattern corresponding to the data that is to be encoded into the molecule via modification of the molecule’s modifiable / photo-modifiable groups.

[0084] In cases of a chemically modifiable moiety which is photo-modifiable, the presence of the photo-modifiable groups which repeat about the length of a long length writable DNA polymer in a known, iteratively repeated spacing can be beneficial to the writing and reading of data on the DNA polymer. For example, it can be difficult to shine light about a very short length of the DNA polymer (e.g., a single nucleotide 0.33 nm range, which is less than a wavelength of light), such that it may not be possible to use light to write data onto DNA polymers at the single nucleotide resolution. The polymers described herein solve for this challenge by providing a DNA polymer which may comprise the photo-modifiable moieties, in a known, iteratively repeated sequence which repeats about the length of a long length writable DNA polymer; data can be written at a known resolution onto the polymer based upon the known spacing of the chemically modifiable moieties. In some cases, writing data can comprise modifying groups of the chemically modifiable moieties with light, with distance of the polymer (or subunit thereof) modified corresponding to a resolution of light that can be applied to a length of the polymer (e.g., writing with visible light of 200 nm may yield resolution of 200 nm, corresponding to 600 bp). In some cases, the known, iteratively repeated sequence / spacing of the chemically modifiable moieties can permit for binary code to be coded by groups of 20 moieties (e.g., at a 28 bp spacing of the second portion of the polymer subunits), providing a means of reliably writing binary code onto the writable DNA polymer via modified and unmodified states of the chemically modifiable moieties using commercially available light sources (e.g., by writing in clusters of 20 moieties). iteratively repeated sequence / spacing of the chemically modifiable moieties also benefits reading the data as the known, iteratively repeated sequence / spacing of the chemically modifiable moieties permits for a reliable identification of written vs. unwritten state (e.g., modified vs unmodified moieties), which may correspond to 0 or 1 in binary code.

[0085] In some examples, modifiable moieties are attached to the nucleobases of the molecule (e.g., polymer). Modifying the modifiable moieties encodes data into the molecule (e.g., polymer). In some examples, measuring the property of the modified moiety (e.g., nucleobase) comprises measuring a signal indicative of a property of the moiety (e.g., nucleobase), a structure, or a sequence thereof, a modification thereof, and / or a light emitted from the modified moiety under certain conditions. For example, in some cases, the molecule used for data storage is a nucleic acid molecule comprising a plurality of modifiable nucleobases, such that the nucleobases are modifiable, thereby generating a modified nucleobase encoding a piece of data into the molecule. For example, nucleobases along the length of the molecule (nucleic acidmolecule configured for data storage, polymer subunits and sections thereof) may be modified, thereby generating modified nucleobases in the molecule. In some cases, modifying the modifiable groups incorporated in predefined clusters in the molecule that may reduce the cost and allow for clusters of the modifiable nucleobases to store date as a single bit.

[0086] In some examples, measuring the property of the modified moiety (e.g., nucleobase) comprises measuring a signal indicative of a property of the moiety (e.g., nucleobase), a structure, or a sequence thereof, a modification thereof, and / or a light emitted from the modified moiety under certain conditions. In some cases, reading the data stored on the molecule (e.g., polymer), or decoding the encoded molecule (e.g., modified polymer, or subunit / section thereof) may be performed by detecting an optical or spectral signal from the modified molecule. The molecule and the modified molecule may have optical properties such that once measured / detected, they may provide information about the molecule or the modified molecule. In some cases, writing the data to the molecule (e.g., polymer) may be performed by applying an optical or spectral signal (e.g., light source). Once the modification is applied, the optical properties of the molecule change, thereby generating the modified molecule. As such, detecting an optical property of the modified molecule and / or the sections or nucleobases thereof can provide access to the information / data. This may be referred to as data reading or molecule decoding (decoding the encoded molecule). Reading the modified / encoded molecule via an optical signal can be a very efficient and fast method of data retrieval. For example, this method may be significantly faster, less labor intensive, and less expensive than sequencing the molecule. Sequencing may further involve sample preparation which adds to the time and labor of the method. Optical decoding can be done very quickly, and in some cases even, on-the-fly (during a screen or experiment, as soon as the molecule is modified and / or as soon as the encoding is done). However, measuring the identity of the nucleobase in the polymer (and modified portions thereof) can also be performed by sequencing. .

[0087] In some cases, the molecule (e.g., the polymer) comprises a moiety with optical properties. The optical properties of the moiety can be modified to encode data into the molecule. For example, the modifiable moiety comprises or is a tag, a dye (e.g., a tag or dye attached to a nucleobase of the molecule). Modifying the moiety leads to encoding data into the molecule at the modified location / moiety. Detecting / measuring a signal from the tag, dye, or label indicative of an optical property of the modified section, region, or nucleobase of the modified molecule provides access to the information / data encoded into the molecule upon application of the stimulus. This may be referred to as reading / decoding the molecule to retrieve the data. In some cases, the signal is a fluorescent signal. In some cases, the tag, the dye, and / orthe label is a fluorescent tag. The fluorescent signal can be detected using any suitable fluorescence detector. In some examples, modification comprises bleaching a fluorescent dye in the molecule. In some examples, modification comprises activating a fluorescent dye in the molecule.

[0088] In some cases, a system comprising an optical, spectral, or fluorescent detector can be provided or obtained to detect a signal from the modified molecule, such as to read the molecule and provide access to the information and data encoded / written into the molecule using the methods, molecules, compositions, and systems of the present disclosure. The molecules used for data storage comprise certain characteristics, features, properties, and embodiments that make them useful for the aforementioned applications. Such characteristics and properties as well as methods for achieving them are further elaborated on in the following sections of the disclosure.

[0089] In some cases, the molecules comprise polymers, nucleic acid molecules, or polynucleotides. In some cases, such molecules comprise a length that is longer than a certain threshold, such that the length of the molecule may be sufficient to store or contain sufficient or useful amounts, volumes, or sizes of data and information. Therefore, the length of the molecule and a variability among the lengths of a plurality of manufactured molecules may be an important feature and it is elaborated on in further detail herein.

[0090] In some embodiments, the molecules of the present disclosure comprise modifiable groups (e.g., modifiable nucleotides). In some cases, the molecule may comprise one or more modifiable groups along its length, in predefined locations on the molecule. In some examples, the modifiable group may be incorporated in the molecule chemically, such as via a chemical bond, in some cases covalently bound along the length of the molecule. In some examples, the molecule may comprise a DNA construct (e.g., double stranded DNA construct). In some embodiments, the molecule carries an array of modifiable groups (a plurality of modifiable groups) along the length of the molecule with defined intervals between the modifiable groups. The defined intervals may facilitate writing data into the polymer, for example with light, by providing a modifiable group within the illuminated portion of the polymer. The defined intervals may facilitate reading each modifiable group (a group that is configured to be modified or that is modified upon application of a modifying stimulus) separately without interference of the modifiable groups with one another. In some examples, a molecule comprises one or more types of modifications (e.g., different chemical modifications). The molecule can accommodate a range of chemical modifications, in some cases, a wide range of chemical modifications. In some cases, a plurality of different types of modifications can be done on the same molecule.

[0091] In some embodiments, the molecule may have a defined length. The length of the molecule can be any length described anywhere in the present disclosure. In some cases, the length is at least about 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65 kilo base pairs (kbp), or longer. The length of the molecule can be controlled. For example, once a plurality of copies of the same molecule are synthesized and manufactured using the methods of the present disclosure, the sizes of the molecules among a group of synthesized or manufactured molecules are substantially uniform with a low molecule-to-molecule variability in length of the molecules (e.g., in a manufactured batch). In some examples, a coefficient of variability among the molecules is less than about 20%, 18%, 15%, 12%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1% or less.

[0092] In an aspect, provided herein is a polymer molecule. The polymer molecule comprises a plurality of subunits across its length. In some cases, the molecule or the polymer molecule is a nucleic acid molecule and / or a polynucleotide. A subunit of the plurality of subunits of the molecule comprises a first section and a second section. In one embodiment, the second section is 3’ to the first section. The first section is composed of one or more nucleobases. In some examples, the first section is composed of up to three nucleobases. In some examples, the first section is composed of 3 nucleobases, 2 nucleobases, or 1 nucleobase. In some examples, the second section comprises at least 4 nucleobases, at least one of which is different from the nucleobases in the first section.

[0093] In some examples, the nucleobases are natural or naturally occurring nucleobases. In some examples, the nucleobases may be unnatural nucleobases. For example, the nucleobases may be synthetic nucleobases.

[0094] In an aspect, provided herein is a polymer comprising a plurality of subunits across the length of the polymer, each subunit comprising a first section and a second section 3’ to the first section, wherein the first section is composed of up to three different nucleobases, and the second section comprises at least a fourth nucleobase different from the nucleobases in the first section.

[0095] In some examples, the first sections of the plurality of subunits may have the same length and / or composition of nucleobases. In some examples, the second sections of the plurality of subunits may have the same length and / or composition of nucleobases. In some examples, the second sections of the plurality of subunits may have a different length and / or a different composition of nucleobases. In some examples, the second sections of the plurality of subunits comprise a T nucleobase. In some examples, the second sections of the plurality of subunits comprise a U nucleobase.

[0096] In some examples, repeating sequences may be used in the molecule. For example, the molecule may be a polymer comprising a plurality of repeating monomers. In some cases, the molecule may be a polynucleotide with a plurality of repeating sequences therein. In some cases, the molecule may be a DNA with a plurality of repeating sequences therein. The sequences are according to the embodiments described in further detail anywhere herein. In some cases, the plurality of sequences may be repeated. The plurality of sequences may comprise repeating modifiable groups. In some cases, the repeating modifiable groups may have uniform spacing between them. The size of the molecule may be tightly controlled and uniform among a batch of manufactured molecules. The synthesis and manufacture methods provided herein facilitate some or all of these molecule features. The synthesis method is further elaborated on throughout the present disclosure.

[0097] As is referenced above, there are a number of benefits associated with a writable DNA polymer comprising chemically modifiable moieties in a known, iteratively repeated sequence which repeats about the length of a long length writable DNA polymer. For instance, such features can allow for data can be written using light by applying light at a known resolution consistent with the spacing of known, iteratively repeated chemically modifiable moieties, and can be especially useful for storing or reading data as binary code where “0” and “1” bits corresponded to unmodified and modified states. However, the spacing between the modifiable nucleobases / moieties is important in providing for such features, as well as the sequence of the other portions of the DNA polymer are important for allowing for high fidelity replication and assembly of very long length DNA polymers which can store large amounts of data (and which also maintain the iteratively repeated spacing between the modifiable nucleobases / moieties). For instance, it is observed that DNA polymers which comprise long homopolymer tracks are not replicated or amplified with high fidelity, due to the tendency of DNA polymerases to skip homopolymer tracks. In some examples, the first sections of the plurality of subunits may not include a homopolymer longer than a 7-mer. In some examples, the first sections of the plurality of subunits may not include a homopolymer longer than a 6-mer. In some examples, the first sections of the plurality of subunits may not include a homopolymer longer than a 5-mer. In some examples, the first sections and second sections of the plurality of subunits do not include a homopolymer longer than a 14-mer. In some examples, the first sections of the plurality of subunits may not include a homopolymer longer than a 13-mer. In some examples, the first sections of the plurality of subunits may not include a homopolymer longer than a 12-mer. In some examples, the first sections of the plurality of subunits may not include a homopolymer longer than a 11-mer. In some examples, the first sections of the plurality of subunits may notinclude a homopolymer longer than a 10-mer. In some examples, first sections of the plurality of subunits comprise at least one G nucleobase and at least one C nucleobase, wherein a GC ratio among the nucleobases of the first section is about 40%-60%. In some embodiments, the first sections of the plurality of subunits comprises a GC ratio of about 50%. In some examples, the GC ratio is at least about 40%, 45%, 50%, 50%, or 55%. In some examples, the GC ratio is at most about 60%, 55%, 50%, or 45%. In some embodiments, the first sections of the plurality of subunits not comprising a homopolymer track and / or the first sections of the plurality of subunits comprising a GC ratio of about 40%-60% permits for the replication and assembly of very long length DNA polymers which can store large amounts of data as binary code (for instance, due to maintaining the spacing of known, iteratively repeated chemically modifiable moi eties about the length of the extended polymer).

[0098] In some examples, the first sections of the plurality of subunits each comprise up to 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, or less nucleobases.

[0099] In some cases, a molecule may comprise incorporation of modifiable / modified groups with substantially homogenous or uniform spacing along the molecule. In some cases, the molecule may be DNA with incorporation of modifications to its nucleobases with substantially homogeneous or uniform spacing between the modified nucleobases / moieties. In some cases, the modifications may be closely spaced. For example, in some cases, the spacing between the modified moieties / nucleobases / groups is at most about 200, 150, 100, 80, 90, 70, 60, 50, 40, 30, 20, 10, 9, 8, 7, 6, 5 or 4 bp. In some cases, the spacing is from about 4 bp to about 10 bp, from about 4 bp to about 20 bp, from about 4 bp to about 30 bp, from about 4 bp to about 50 bp, or from about 4 bp to about 100 bp.

[0100] In some examples, the first section may be composed of two or more different nucleobases. In some examples, the polymer may comprise a sequence defined by the formula: [(Y)n(X)m]p, wherein Y comprises a plurality of nucleobase selected from A / C / G, and X comprises a fourth nucleobase not selected from A / C / G. In some examples, n is less than 100, 50, 28, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, or 3. In some examples, n is at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 13, 14, 27, 28, 49, 50, 99, or 100. In some examples, n is 4-14. In some examples, m is less than 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, or 3. In some embodiments, m is at least 2, 3, 4, 5, 6, 7, 8, 9, or 10. In some examples, p is at least 3, 4, 5, 6, 7, 8, 9, 10, 100, 500, 1,000, 5,000, 10,000, 50,000, or 100,000. In some examples, n=l, m=l, and p<2, 3, 4, 5, 6, 7, 8, 9, or 10. In some examples, Y is the first section of polymer subunits, and X is the second section of the polymer subunits. In some examples, X is a single fourth nucleobase not selected from A / C / G, m is 1, andp is 1 (e.g., [(A / C / G)nT)). Note that n refers to a total length of the section of (A / C / G) section in base pairs, and not necessarily to a number of repeats of a sequence therein.

[0101] In some examples, the second section may be repeated at an interval defined by a length of the first section. In some examples, the length of each first section may be defined by a maximum variation being less than 0.3, the maximum variation being equal to a median absolute deviation of the length of the first sections divided by a median length of the first sections. In some examples, the length of each first section may be from 4-100 bp. In some examples, the length of each first section may be up to 100 bp.

[0102] In some examples, the polymer subunits define at least about 90%, 95%, 98%, or 99% of the polymer. In some examples, the polymer may further comprise a sequence-specific cleavable site at the 5’ end of the 5’ outermost subunit and / or 3’ end of the 3’ outermost subunit. In some examples, the polymer further comprises a sequence-specific cleavable site at each of the 5’ and 3’ ends of each subunit.

[0103] In some examples, the polymer may further comprise a second sequence-specific cleavable site at the 5’ end of the 5’ outermost subunit. In some examples, the sequence-specific cleavable site can be cut by an endonuclease that cuts only one of two strands of DNA. In some examples, the sequence-specific cleavable site can be cut by an endonuclease that cuts both strands of DNA. In some embodiments, the sequence-specific cleavable site can be cut by a golden gate assembly endonuclease. The presence of the sequence-specific cleavable site that can be cut by an endonuclease that cuts only one of two strands of DNA (e.g., a nickase), can provide for nick translation and incorporation of the chemically modifiable moieties into the long length DNA polymer at the known, iteratively repeated interval about the length of the extended polymer (see FIG. 4). The presence of the sequence-specific cleavable site that can be cut by an endonuclease that cuts both strands of DNA can provide for linearization of plasmid DNA constructs. The presence of the sequence-specific cleavable site can be cut by a golden gate assembly endonuclease can provide for the assembly of a plurality of shorter length DNA polymer fragments into an extended length DNA polymer, which is long enough to store commercially relevant amount of data (as compared to shorter length polymers). In some examples, the polymer is at least 10k, 20, 30k, 40k, 50k, 60k, 70k, 80k, 90k, 100k, or 200 k units in length.

[0104] In some examples, the second section may comprise an irreversibly convertible moiety. In some embodiments, the irreversibly convertible moiety may be attached to the fourth nucleobase in the second section. In some embodiments, the irreversibly convertible moiety may be light activated, redox activated or chemically activated. In some embodiments, theirreversibly convertible moiety comprises fluorescein, CF488A, ATTO488, Alexa Fluor 488, Cy3, Alexa Fluor 546, Alexa Fluor 555, ATTO643, ATTO647N, ATTO655, or Cy5. In some embodiments, the irreversibly convertible moiety comprises an uber dye. In some embodiments, the irreversibly convertible moiety comprises azido dye conjugated to the DNA with click chemistry.

[0105] In some examples, the first section may not include an irreversibly convertible moiety. In some examples, the polymer may be at least 10k, 20, 30k, 40k, 50k, 60k, 70k, 80k, 90k, 100k, or 200 k units in length.

[0106] In some examples, the polymer may encode at least 100, 200, 300, or 350 bits of binary data. In some examples, the polymer comprises at least 250 irreversibly convertible moieties.

[0107] In an aspect, provided herein may be a composition comprising a plurality of polymers. The plurality of polymers may comprise one or more polymers described anywhere in the present disclosure, wherein the polymers of the plurality of polymers are at least 7 kbp in length each, and the composition does not comprise greater than 5%, 3%, or 1% of truncated polymers less than 7 kbp in length.

[0108] In an aspect, provided herein is a composition comprising a plurality of polymers, such that the plurality of the polymers of the compositions may comprise one or more polymers from the polymers described anywhere in the present disclosure, the polymers of the plurality of polymers may be at least 7 kbp in length, and a length of the first section of the subunits is substantially the same among the polymers of the plurality of polymers.

[0109] In an aspect, provided herein is a composition comprising a plurality of the polymers, such that the plurality of polymers comprises one or more polymers from the polymers described anywhere in the present disclosure, the polymers of the plurality of polymers are at least 7 kbp in length, and a variation of a length of the plurality of polymers does not exceed 10%, 5%, or 1%. In some examples, the variation of the length of the plurality of polymers is at most about 10%, 8%, 7%, 6%, 5%, 1% or less. The compositions comprising the plurality of the polymers can be produced by replicating / amplifying and assembling shorter length polymer fragments into extended length polymers. The composition comprising the plurality of the polymers which do not have a variation of a length of the plurality of polymers exceeding 10%, 5%, or 1% can permit for reliable writing of large amounts of data due to the successful construction of a large amount of long length polymers. In some examples, the plurality of the polymers in the composition is at least 10k, 20, 30k, 40k, 50k, 60k, 70k, 80k, 90k, 100k, or 200 k units in length.

[0110] In an aspect, provided herein is a composition comprising a plurality of polymers comprising a polymer described anywhere in the present disclosure, such that the polymers of the plurality of polymers are at least 7 kbp in length, and there is at least 95%, 98%, or 99% similarity between the sequences of the polymers of the plurality of polymers. The compositions comprising the plurality of the polymers can be produced by replicating / amplifying and assembling shorter length polymer fragments into extended length polymers. The composition comprising the plurality of the polymers which have 95%, 98%, or 99% similarity in the composition can permit for reliable writing of large amounts of data due to the successful construction of long length polymers which maintain the spacing between the modifiable nucleobases / moieties that were originally present in the shorter fragments. The comprising the plurality of the polymers which have 95%, 98%, or 99% similarity in the composition may be due to the features of the DNA polymers described herein, for example, the GC content, the lack of homopolymer tracks, and the structure of the subunits (e.g., [(A / C / G)nT)).

[0111] Various approaches can be taken for designing the molecules of the present disclosure. Examples comprise oligonucleotides, short oligonucleotides, rolling circle amplification products, and plasmid DNA. In some examples, synthetics oligonucleotides can be ligated to produce polymers. In some cases, in this approach, it may be difficult to control the length of the molecule resulting in a mixture comprising molecules of varying lengths, and ligation can be blocked by modifications in the DNA. Achieving a homogeneous batch of molecules with substantially uniform lengths may be challenging. In some embodiments, the methods of the present disclosure may solve this challenge and enable generating a batch of molecules with substantially uniform lengths.

[0112] Other example approaches for generating the molecules of the present disclosure include producing plasmid DNA with the aid of one or more bacteria. In some cases, naturally produced DNA plasmids using such technique may not have defined, modifiable positions regularly along their length. Therefore, synthetically producing the molecule (e.g., plasmid DNA) using the methods of the present disclosure may yield better results, at least in terms of uniformity of the lengths of the molecules and uniformity of spacing of modifiable positions. In some embodiments, such manufacturing methods enable incorporation of modifications with substantially homogeneous / uniform spacing along the length of the molecule (e.g., DNA) as well as uniform molecule lengths in the batch. The modifications are in some cases closely spaced, as described elsewhere herein. Incorporating repeating DNA sequences in the molecule is one way to facilitate achieving regular spacing of modifiable groups; however, in some cases, synthesizing, assembling, and replicating repetitive DNA may be challenging using enzymaticand biological methods. For example, replicating polymerases often skip repeating units which may result in failure of such method. Furthermore, recombination can occur with repeating sequences and result in skipped or omitted segments.

[0113] In some cases, a combination synthesis method may be used to generate the molecules of the present disclosure, which may have certain advantages over other methods. For example, in some cases, the manufacture methods in the present disclosure comprise producing a baseline modifiable DNA by or with the aid of bacteria followed by synthetically building / encoding modifications in repetitive or semi-repetitive locations after the baseline modifiable DNA is produced by bacteria. In some cases, the molecule manufacturing methods presented herein may enable the incorporation of more than one type of modification in the same molecule (e.g., DNA)

[0114] Provided herein are methods of manufacturing of the molecules of the present disclosure. In some embodiments, the molecules may be configured to and capable of encoding data. Writable / encodable molecules can be manufactured ahead of data encoding which can provide various advantages elaborated on throughout the present disclosure, including efficient, fast, non-labor-intensive, and inexpensive molecule manufacture methods, easy, fast, efficient, and inexpensive encoding / writing and decoding / reading of data into and from the molecules among other advantages. The molecules have certain features designed to be optimal for the intended application(s). Such features are elaborated on throughout the present disclosure including in the preceding paragraphs, in the figures, and examples. The manufacture methods further provided herein enable achieving such molecule features and characteristics. Generating molecules with uniform length is among the example features of the molecule that can be achieved upon following the methods of manufacture presented herein.

[0115] In an aspect, provided herein is a method for manufacturing a writable polymer comprising combining a plurality of the polymers of the preceding embodiments to create an extended polymer. In some cases, combining comprising combining at least 10, 100, 1,000, or 10,000 polymers.

[0116] In some examples, the method further comprises providing a destination vector comprising a sequence-specific cleavable site that can be cut by an endonuclease that cuts both strands of DNA.

[0117] In some examples, the method further comprises contacting the destination vector and the plurality of the polymers of described in the preceding paragraphs with an endonuclease that cuts both strands of DNA and which leaves a nucleotide overhang at the cleavage site, such as to produce a plurality of linearized fragments.

[0118] In some examples, the method further comprises hybridizing the plurality of linearized fragments to produce a plurality of hybridized fragments. In some examples, the method further comprises contacting the plurality of hybridized fragments with a ligase and ligating the plurality of hybridized fragments, thereby combining the plurality of the polymers to create the extended polymer. In some examples, the extended polymer is at least 7 kbp in length.

[0119] In some examples, the method further comprises combining a second plurality of the polymers (the plurality of the polymers described anywhere herein, such as in the preceding paragraphs) with the extended polymer to produce a second extended polymer. In some examples, the method further comprises contacting the extended polymer and the second plurality of the polymers with an endonuclease that cuts both strands of DNA and which leaves a nucleotide overhang at the cleavage site, to produce a plurality of linearized fragments.

[0120] In some examples, the method further comprises hybridizing the plurality of linearized fragments to produce a plurality of hybridized fragments. In some examples, the method further comprises contacting the plurality of hybridized fragments with a ligase and ligating the plurality of hybridized fragments, thereby combining the second plurality of the polymers of with the extended polymer to produce the second extended polymer. In some examples, the second extended polymer is at least 10 kbp, 20 kbp, 30 kbp, 40 kbp, 50 kbp, 75 kbp, 100 kbp, 150 kbp, or 200 kbp in length.

[0121] In some examples, the method further comprises contacting the first or the second extended polymer with an endonuclease that cuts only one of two strands of DNA to produce a polymer comprising a nick site. In some examples, the nick site is 5’ of at least one polymer subunit.

[0122] In some examples, the method further comprises contacting the polymer comprising the nick site with a DNA polymerase and synthesizing a new polymer. In some examples, the DNA polymerase incorporates an irreversibly convertible moiety the second section of the new polymer, such that the new polymer is a polymer described anywhere in the present disclosure.Computer systems

[0123] The present disclosure provides computer systems that are programmed to implement methods of the disclosure. FIG. 11 shows a computer system 1101 that is programmed or otherwise configured to modify polymers. The computer system 1101 can regulate various aspects of writing system of the present disclosure, such as, for example, the light source intensity and / or wavelength. The computer system 1101 can be an electronic device of a user ora computer system that is remotely located with respect to the electronic device. The electronic device can be a mobile electronic device.

[0124] The computer system 1101 includes a central processing unit (CPU, also “processor” and “computer processor” herein) 1105, which can be a single core or multi core processor, or a plurality of processors for parallel processing. The computer system 1101 also includes memory or memory location 1110 (e.g., random-access memory, read-only memory, flash memory), electronic storage unit 1115 (e.g., hard disk), communication interface 1120 (e.g., network adapter) for communicating with one or more other systems, and peripheral devices 1125, such as cache, other memory, data storage and / or electronic display adapters. The memory 1110, storage unit 1115, interface 1120 and peripheral devices 1125 are in communication with the CPU 1105 through a communication bus (solid lines), such as a motherboard. The storage unit 1115 can be a data storage unit (or data repository) for storing data. The computer system 1101 can be operatively coupled to a computer network (“network”) 1130 with the aid of the communication interface 1120. The network 1130 can be the Internet, an internet and / or extranet, or an intranet and / or extranet that is in communication with the Internet. The network 1130 in some cases is a telecommunication and / or data network. The network 1130 can include one or more computer servers, which can enable distributed computing, such as cloud computing. The network 1130, in some cases with the aid of the computer system 1101, can implement a peer-to-peer network, which may enable devices coupled to the computer system 1101 to behave as a client or a server.

[0125] The CPU 1105 can execute a sequence of machine-readable instructions, which can be embodied in a program or software. The instructions may be stored in a memory location, such as the memory 1110. The instructions can be directed to the CPU 1105, which can subsequently program or otherwise configure the CPU 1105 to implement methods of the present disclosure. Examples of operations performed by the CPU 1105 can include fetch, decode, execute, and writeback.

[0126] The CPU 1105 can be part of a circuit, such as an integrated circuit. One or more other components of the system 1101 can be included in the circuit. In some cases, the circuit is an application specific integrated circuit (ASIC).

[0127] The storage unit 1115 can store files, such as drivers, libraries and saved programs. The storage unit 1115 can store user data, e.g., user preferences and user programs. The computer system 1101 in some cases can include one or more additional data storage units that are external to the computer system 1101, such as located on a remote server that is in communication with the computer system 1101 through an intranet or the Internet.

[0128] The computer system 1101 can communicate with one or more remote computer systems through the network 1130. For instance, the computer system 1101 can communicate with a remote computer system of a user (e.g., to select the writing system settings). Examples of remote computer systems include personal computers (e.g., portable PC), slate or tablet PC’s (e.g., Apple® iPad, Samsung® Galaxy Tab), telephones, Smart phones (e.g., Apple® iPhone, Android-enabled device, Blackberry®), or personal digital assistants. The user can access the computer system 1101 via the network 1130.

[0129] Methods as described herein can be implemented by way of machine (e.g., computer processor) executable code stored on an electronic storage location of the computer system 1101, such as, for example, on the memory 1110 or electronic storage unit 1115. The machine executable or machine readable code can be provided in the form of software. During use, the code can be executed by the processor 1105. In some cases, the code can be retrieved from the storage unit 1115 and stored on the memory 1110 for ready access by the processor 1105. In some situations, the electronic storage unit 1115 can be precluded, and machine-executable instructions are stored on memory 1110.

[0130] The code can be pre-compiled and configured for use with a machine having a processer adapted to execute the code, or can be compiled during runtime. The code can be supplied in a programming language that can be selected to enable the code to execute in a precompiled or as-compiled fashion.

[0131] Aspects of the systems and methods provided herein, such as the computer system 1101, can be embodied in programming. Various aspects of the technology may be thought of as “products” or “articles of manufacture” typically in the form of machine (or processor) executable code and / or associated data that is carried on or embodied in a type of machine readable medium. Machine-executable code can be stored on an electronic storage unit, such as memory (e.g., read-only memory, random-access memory, flash memory) or a hard disk.“Storage” type media can include any or all of the tangible memory of the computers, processors or the like, or associated modules thereof, such as various semiconductor memories, tape drives, disk drives and the like, which may provide non-transitory storage at any time for the software programming. All or portions of the software may at times be communicated through the Internet or various other telecommunication networks. Such communications, for example, may enable loading of the software from one computer or processor into another, for example, from a management server or host computer into the computer platform of an application server. Thus, another type of media that may bear the software elements includes optical, electrical and electromagnetic waves, such as used across physical interfaces between local devices, throughwired and optical landline networks and over various air-links. The physical elements that carry such waves, such as wired or wireless links, optical links or the like, also may be considered as media bearing the software. As used herein, unless restricted to non-transitory, tangible “storage” media, terms such as computer or machine “readable medium” refer to any medium that participates in providing instructions to a processor for execution.

[0132] Hence, a machine readable medium, such as computer-executable code, may take many forms, including but not limited to, a tangible storage medium, a carrier wave medium or physical transmission medium. Non-volatile storage media include, for example, optical or magnetic disks, such as any of the storage devices in any computer(s) or the like, such as may be used to implement the databases, etc. shown in the drawings. Volatile storage media include dynamic memory, such as main memory of such a computer platform. Tangible transmission media include coaxial cables; copper wire and fiber optics, including the wires that comprise a bus within a computer system. Carrier-wave transmission media may take the form of electric or electromagnetic signals, or acoustic or light waves such as those generated during radio frequency (RF) and infrared (IR) data communications. Common forms of computer-readable media therefore include for example: a floppy disk, a flexible disk, hard disk, magnetic tape, any other magnetic medium, a CD-ROM, DVD or DVD-ROM, any other optical medium, punch cards paper tape, any other physical storage medium with patterns of holes, a RAM, a ROM, a PROM and EPROM, a FLASH-EPROM, any other memory chip or cartridge, a carrier wave transporting data or instructions, cables or links transporting such a carrier wave, or any other medium from which a computer may read programming code and / or data. Many of these forms of computer readable media may be involved in carrying one or more sequences of one or more instructions to a processor for execution.

[0133] The computer system 1101 can include or be in communication with an electronic display 1135 that comprises a user interface (UI) 1140 for providing, for example, light source settings of the writing system. Examples of UI’s include, without limitation, a graphical user interface (GUI) and web-based user interface.

[0134] Methods and systems of the present disclosure can be implemented by way of one or more algorithms. An algorithm can be implemented by way of software upon execution by the central processing unit 1105. The algorithm can, for example, control the wavelength and duration of light emission of the light source described herein.

[0135] While preferred embodiments of the present invention have been shown and described herein, it will be obvious to those skilled in the art that such embodiments are provided by way of example only. It is not intended that the invention be limited by the specific examplesprovided within the specification. While the invention has been described with reference to the aforementioned specification, the descriptions and illustrations of the embodiments herein are not meant to be construed in a limiting sense. Numerous variations, changes, and substitutions will now occur to those skilled in the art without departing from the invention. Furthermore, it shall be understood that all aspects of the invention are not limited to the specific depictions, configurations or relative proportions set forth herein which depend upon a variety of conditions and variables. It should be understood that various alternatives to the embodiments of the invention described herein may be employed in practicing the invention. It is therefore contemplated that the invention shall also cover any such alternatives, modifications, variations or equivalents. It is intended that the following claims define the scope of the invention and that methods and structures within the scope of these claims and their equivalents be covered thereby.EXAMPLES

[0136] Provided herein are various examples for molecules of the present disclosure, their subsections and assemblies, labeling and tags, methods of use (method of data encoding / writing and decoding / reading), and methods of manufacture of the molecules. The examples are not meant to be limiting.

[0137] In some examples, a molecule of the present disclosure contains pseudo-repeats of sequences. In some examples, the molecule comprises one or more nicking sites. In some examples, the molecule comprises one or more specific bases downstream of the nicking site for uniform labeling. In some embodiments, the molecule comprises one or more nicking sites or an array of nicking sites. The molecule further comprises modifiable groups. The modifiable groups may be downstream of the nicking sites. In some examples, the molecule comprises a single nicking site.

[0138] Nicking sites that can be labeled can be used to label natural DNA at specific nicking sites, which are encoded by restriction endonuclease recognition sequences. In this method, DNA is treated with “nickase” to create a single strand break that allows DNA polymerase to incorporate modified nucleotides downstream of that location by extending the 3’- end of the nick. Therefore, one way to create a modifiable DNA is potentially to include an array of nicking sites that can be nicked or labeled. However, there are two drawbacks to this method. The first is that nicking sites can’t be placed too close to each other, because the low melting temperature of short single stranded DNAs might cause them to denature from the other strand. Second, a high number of nicking sites would require either a long digestion period or high concentration of nickase. This might risk an incomplete labeling. Generating a molecule with asingle nicking site followed by an array of T nucleotides such as in the example shown in FIG. 1 of the present disclosure may help address these drawbacks and work better.Example 1: DNA polymer configured to encode data

[0139] FIG. 1 shows an example of a molecule of the present disclosure. The molecule shown in FIG. 1 is DNA polymer configured to encode data or information. The molecule comprises a single nicking site followed by a plurality of Ts paced with an equal number of other nucleotides in between. The molecule is a double-stranded DNA plasmid (a circular doublestranded molecule). The molecule comprises a first strand and a second strand. In the figure, sections represented with upside down letters represent entities, subsections, or moieties on the opposite strand (e.g., the second strand). From left to right the sections of the molecule comprise: an origin of replication (P15A origin of replication) on a first strand followed by a Chloram-phenicol resistance gene, a “Nt.BbvCl” nicking site, and a plurality of repeating units with the formula (A / C / G)nT as elaborated on throughout the present disclosure on the same strand, a “Nt.NspQl” nicking site on the opposite / complement strand followed by a restriction digest site (Notl). This can facilitate the linearization of the molecule. As such, the (A / C / G)nT repeating sequence is flanked by two nicking sites that can be cleaved by Nt. BbvCI and Nt.BspQI, respectively. The spacing between T nucleotides can range from 3 to 99 bp. The sequence of the (A / C / G)nT repeats were generated by a customed Python script to ensure GC content remains close to 50%, the absence of homopolymer tracts, and the correct placements of Golden Gate assembly overhangs.

[0140] In some alternative designs, colEl high copy origin of replication was used for cloning. However, it was found that when T nucleotides were spaced longer than 14 bp, it became difficult to find correctly assembled plasmids, with most clones carrying mostly / only truncated plasmids. Moreover, the carrying these plasmids were often smaller than regular colonies. Incorporating a Pl 5 A low copy origin of replication led to fully assembled products and achieving normal colony sizes.

[0141] Spacings of 4, 7, 14, 28, 50, and 100 bp long were tested. Specifically with DNA tape wherein the DNA comprises long spacing, a Pl 5 A low copy origin of replication worked better than other alternatives.

[0142] In the design method illustrated in FIG. 1, the nick site provides the entry point for DNA polymerase that replaces the nucleotides downstream. By using a modified dUTP analog, the newly synthesized strand contains an array of modifiable positions with equal or nearly equal intervals (substantially uniform). To prevent recombination of the plasmid duringreplication in bacteria (which can happen with repetitive sequences), computer programs were to randomize the nucleotides between T nucleotides to limit sequence similarity, maintain GC content, and prevent long homopolymers. Once the fragments (e.g., about 500-600 bp) were synthesized, Golden Gate Assembly method was used to only expose the termini of each fragment to ensure proper assembly. The DNA was then transformed into E. coli strain DH10B, a strain that accommodates long DNA and is poorly recombinogenic, to ascertain the integrity of the DNA plasmid.

[0143] To perform the Golden Gate assembly, a kit sold under trademark NEB® Golden Gate Assembly kit was used following the manufacturer’s protocol. As an example, for a 30 uL reaction, 10 ng of each fragment was mixed with 20 ng of destination vector. It further contained 200 U T4 ligase, 50U BbsI, 1 mM ATP, and lx rCutSmart buffer (all from NEB). The reaction volume was brought up to 30 uL with H2O. The reaction was cycled 30-60 times between 37C for 5 minutes and 16C for 5 minutes. Before transformation, the reaction was heated at 60C for 5 minutes. 2 uL of the reaction was used for transformation using NEB® 10-beta Competent E. coli, following manufacturer's protocol.

[0144] With continued reference to FIG. 1, the modifiable nucleotides in the molecule are T nucleotides. T nucleotides were chosen as modifiable nucleotides for the first strand of the molecule. This allows to use modified dUTP variants including, for example, fluorescent dyes, alkyne groups for click-chemistry, or biotins for protein binding. In some examples, in order to modify the molecule at its modifiable sites (T nucleotide and the corresponding U on the opposite strand), native dU can be exchanged with a fluorescent due by base excision trapping (BETr), providing an example route for DNA modification. This can be performed by applying a stimulus to the modifiable site / nucleotide according to the methods elaborated on anywhere herein.

[0145] The manufactured molecule (engineered DNA tape) was characterized by gel electrophoresis, sequencing, spectroscopy, and microscopy. It was demonstrated that despite the presence of repetitive sequences in the DNA, the DNA molecule was successfully synthesized with up to 40 kb in length that stably transformed and replicated in E. coli. It was further demonstrated that these DNA can be homogenously labeled with fluorescent dyes and stretched under a microscope. Finally, dual fluorescent labeling and photo-modulation was performed and verified by a spectrometer.

[0146] Design of the DNA polymer PCR amplification of highly repetitive sequences was known to cause laddering, due to shortening and expansion of DNA during polymerase chain reaction (PCR), resulting into fragments with variable amounts of repeating units(undesired non-uniformities). For example, it was known that PCR of transcription-activator like effectors (TALEs), which contain multiple -100 nt repeats, often yielded laddered products. Moreover, repetitive DNA sequences are unstable in organisms, often causing increasing or decreasing of the repeating unit. Therefore, in some embodiments, the sequences of the present disclosure were designed such that the interval between T nucleotides were maintained while the nucleotides in between were randomized to prevent generating perfect repeats. In some embodiments, in the methods of the present disclosure, PCR-based assembly methods such as Gibson assembly were avoided to circumvent potential issues with accidental insertion or deletion of repeating units.Example 2: Fabrication of 7.9 kb DNA polymer “tapes”

[0147] To make 7.9 kb plasmids (SEQ 1 to SEQ 4), each plasmid was broken into 10 insert fragments that were synthesized individually. Each fragment included a region of T nucleotides spaced exactly 28 bp apart with A, C, and G filled in between. The region was flanked by a pair of compatible 4-bp overhangs after BbsI cleavage that allowed the fragments to assemble. The first overhang of the first fragment and the second overhang of the last fragment were the same. Each plasmid was made using a different destination vector containing a different pair of 4-bp overhangs such that the resulting plasmids could be further assembled into a longer construct using Bsal. Except for the 4-bp overhangs, all destination vectors shared a Pl 5 A origin of replication and a Chloramphenicol resistant gene for selection (similar to what was shown in FIG. 1). They also carried an RFP between the BbsI sites such that excision of RFP would result in the loss of red color from the bacterial colonies. The method and resulting molecule are shown in FIG. 2. The Golden Gate assembly method was used to construct the four 7.9 kb plasmids with BbsI and T4 DNA ligase (both from New England Biolab (NEB)) according to the standard assembly protocol provided by NEB (60 cycles of 5 min at 37C and 5 min 16C). The reaction mixture was directly transformed into A. coli DH10B afterward. White colonies were picked and their plasmids miniprepped for subsequent analysis. The plasmids were restriction digested with Notl for 15 minutes and run on an agarose gel to determine their linear length. Plasmids with the correct sizes were then sent for whole plasmid sequencing for verification. Upon verification of the actual sequence as compared to the expected sequence, it was verified that the plasmid sequences were substantially identical to designed sequence on the computer.Example 3: construction of a 28 kb DNA polymer “tapes”

[0148] FIG. 3 shows a Second Stage assembly of long DNA polymer. For plasmids longer than 10 kb, a second stage of Golden Gate assembly was utilized. The four plasmids described in Example 1 contained compatible 4-bp overhangs when cut with Bsal. Combinedwith a destination with Kanamycin resistance gene and compatible 4-bp overhangs, a 28 kb plasmid (SEQ 5) was constructed by Golden Gate assembly (FIG. 3) using Bsal and T4 ligase (NEBridge® Golden Gate Assembly Kit) with the same procedure as described in Example 1. The resulting plasmid (SEQ 5) was 28 kb long and contains a unique Notl site for linearization. It also included four Nt.BbvCI sites for initiating nick labeling on one strand and four Nt.BspQI sites for the second strand.Example 4: Nick labeling of DNA polymer “tapes” with modifiable moieties

[0149] FIG. 4 schematically illustrates a method of dual labeling of a DNA tape with fluorescein and Cy5. To label DNA with modifiable nucleotides, fluorescent dyes, for example, a nickase (Nt. BbvCI) was used to cleave one of the DNA strands followed by nick translation with Taq DNA polymerase in the presence of fluorescent dye conjugated dUTP as shown in FIG. 4. To label the second strand DNA, the singly labeled DNA was purified and subjected to the same procedure as described in Example 1 and Example 2, except that the nickase was switched to Nt. BspQI and a fluorescent dye labeled dATP was used. Finally, the nick sites were repaired using a DNA ligase.

[0150] FIG. 5 shows alternative labeling methods to link dyes to DNA. In FIG.5 (Panel A), UBER dyes were conjugated to DNA via base-excision trapping. In FIG.5 (Panel B) Azido dyes were conjugated to DNA via click chemistry. In this example, dye-conjugated dUTP was substituted with native dUTP during the nick translation stage, allowing the DNA to be labeled with dyes via base excision trapping (BETr, FIG. 5). Moreover, alkyne-conjugated dUTP was used in the nick translation stage, allowing downstream labeling with azide-conjugated dyes via click chemistry.

[0151] FIG. 6 shows stretched and labeled DNA visualized under the microscope. In this example, in order to visualize the labeled DNA, DNA was stretched on glass using the FiberComb instrument (Genomic Vision) and observed under a microscope. FIG. 6 (Panel A) shows a linearized 28 kb plasmid with T every 28 bp and labeled with Cy5-dU. FIG. 6 (Panel B) shows a linearized 36 kb plasmid with T every 50 bp and labeled with Cy5-dU. FIG. 6 (Panel C) shows a linearized 40 kb plasmid with T every 4 bp and labeled with alkyne-dU, and reacted with StarRed azide (Abberior) after stretching on glass. The linearized plasmids described herein are embodiments of the data encodable polymers described herein.Example 5: Assembly of -100 kb DNA writable construct

[0152] In this example, the Golden Gate assembly method will be used to build the 100 kb DNA as plasmids. First, four different 28 kb plasmids will be constructed with different pairs of 4-bp overhangs when cut with Bbsl. Then, a destination vector with appropriate 4-bpoverhangs was created with the lowest copy number origin, pSClOl, and an Ampicillin resistant gene. Finally, the four 28 kb plasmids were combined with the destination vector to create a 100 kb DNA plasmid by Golden Gate assembly with BbsI and T4 ligase.Example 6: Assembly and labeling of “striped” calibration DNA

[0153] FIG. 1 shows the assembly of a 28 kb, 200 nm “striped” DNA polymer (e.g., a DNA polymer which comprises the (A / C / G) only sections immediately followed by the [(A / C / G)27T]nrepeats, with the T’s labeled with a chemically modifiable moiety). FIG. 8 shows a striped DNA construct with 200 nanometer (nm) features. To characterize the optical detection system, special DNA tapes were constructed with interleaving regions that include and exclude T nucleotides. This was achieved by assembling 7.9 kb plasmids with alternating -588 bp fragments (equivalent to -200 nm in DNA contour length) with or without T nucleotides. In T- containing fragments, T nucleotides were spaced 28 bp apart. In other fragments, they were made entirely of randomly ordered A, C, and G while maintaining the GC content at about 50% (FIG. 7). Four such plasmids (SEQ 6 to SEQ 9) were constructed as described in Example 1. To assemble the final 28 kb plasmid (SEQ 10), the four plasmids were combined as described in Example 2. When labeled with Cy5-dU as described in Example 3, a “striped” DNA could be observed under the microscope (FIG. 8) in which the T’s are labeled with a chemically modifiable moiety comprising a fluorophore.Example 7: Assembly and labeled of pre-written DNA

[0154] FIG 2. Demonstrates encoding the string “NAIO!” into a DNA tape. In this example, the string “NAIO!” is data or information encoded / written into and stored in the molecule. Only the regions where labeling can occur are shown. The common plasmid parts including the origin of replication and antibiotic resistant genes are omitted from the figure. Prewritten DNA molecules can be assembled to encode optical data, which are useful as calibration and testing tools for reading data from optically encoded DNA. For this reason, a pre-written DNA containing a designed message can be made. For each of the fragments used to create striped DNA tape in Example 5, a version with T nucleotides and a version without T nucleotides were synthesized. Therefore, these fragments can be combined to create tapes with any message in binary form (labeled vs. unlabeled). For example, a message of “NAIO!” can be encoded by ASCII then into binary code and made into a DNA tape with pre-written message (FIG. 9). First, “NAIO!” is encoded into a 40-bit binary string. Second, the binary string is broken down into four 10-bit segments which are built into four 7.9 kb plasmids as described in Example 1. Third, the 4 plasmids are combined into a 28 kb plasmid as described in Example 2,carrying the binary message. For DNA in 100 kb range described in Example 4, the tape is able to encode 120 bits of data with the bit size described here.Example 8: Dual labeled DNA and selective photomodulation of fluorophores

[0155] FIG. 10 shows an example of selective bleaching of a plasmid with T every 4 bp (Panel A) or 7 bp (Panel B) labeled with Fluorescein-dU on one strand and Cy5-dA on the opposing strand. The top figures were measured with the sample bleached with a 470 nm LED and the bottom figures were measured with a 660 nm LED. To demonstrate selective bleaching of a single species of fluorophore on a dual labeled DNA, two 7 kb plasmids with T spaced every 4 or 7 bp were created. The plasmids were dual labeled with Fluorescein-dU on one strand, and Cy5-dA on the second strand such that the two dyes opposed each other on DNA (FIG. 4). The molecules were then bleached using either a 470 nm LED (to bleach Fluorescein) or a 660 nm LED (to bleach Cy5) and measured the remaining fluorescence intensities with a plate reader after each time point. Selectively bleaching with Fluorescein or Cy5 was achieved without affecting the fluorescent intensity of the unbleached dye (Figure 10.). This established the possibility of two-color data writing in a single optically writable DNA tape.

[0156] While preferred embodiments of the present invention have been shown and described herein, it will be obvious to those skilled in the art that such embodiments are provided by way of example only. Numerous variations, changes, and substitutions will now occur to those skilled in the art without departing from the invention. It should be understood that various alternatives to the embodiments of the invention described herein may be employed in practicing the invention. It is intended that the following claims define the scope of the invention and that methods and structures within the scope of these claims and their equivalents be covered thereby.

[0157] DNA Sequences

[0158] SEQ 1ACTGGTCTCCTGCCGGGAGCAGAAAGAACGAAAGAACCTCAGCCAACCGAAACAGGCCGCGAGC CCTGAAAAAGCAGGGCAAAGGAGAGCCCGCTACAACCAAAACGGAAAAAAGAGGCAAGTACCCG AGCAGAGGAGCAAAAACGCAACTAAGGAGGAAGGGACCGAAACAACGAGGTAACGCAAGAAGCA GAAGCGAGGGCACATAAAACCCCACAAGACAAGCCCGGAAAGTACAAAAAGCGAAAAAAAGGAA GCCCAATAAAAGACAACGGGAGACGCAACAAAGATCACAGAGCCAGACAACGAAAAGAAAAATA GCGCCGGAACAAAAAAAGGCGAGAACTGAACCCAAGAACCACAGAAGCACAGGATGAAAACACA GGACCACGGCAACGCAGCTGAAAAAAACAAAAACGCGAGAAAACAATAGAAAACCCAAAACAGA CCCGGGCAGATAGAAAAGAACAACACGAAAAACCCAGCTAGAAACAACAAGGGAGGGCACAAAA AG T AAAAC C C AAGAGAGAAG GAAGAAAAAG T G C AAG C C C C C C GAG C G C C C AC AAAAAAT C AGAA ACAACAAACAGGGCACCAGGAATGAGCAAGCGGAAGAAAAGGACCAAAAATAGACCGGAGAACAACCGGAAACGGCCATAACCGAAACCACGAGGCCAAACAGAAATGAGGCGCACAAAAAAGACGAGGCCACCTGAGCAGAAGCCGCCCCGACGAGAAACATAGGAAGGGCAAGGGACCAGGAGAACAATA AAAGACAGCGGCCGACGAGGCAGGCCTAGGCAGACAACAAAGCGCGCAAACAAATCCAAGGCAC CCCGAACCCGCAGAGGCCTACGAGGGCCAAAACAAAAGCCAAGCGGTGCCAAAAGAGAAACAAC GAAGGGGGGGTCCGCCGAAAGAGAGAACCACCAAAACATAAACAAGAGCGCCAGACCCAGCAAC CATCAGCCACACCGGACAGCAGAAGCAAAATCCACAGAAAAGAGAAACGCAACCAGAATAAAGC AAAACCGCCACACGAAGAGAAGTAACAAAGAACCCCACAACGGGCAGCGGTCGGGAGCGAAGGA GAACACGACGACGGTGCGCACAACAAACAACAAGCACAGCGCTAGGGCCGACCAGGGAGAAGCA AGGAACTAAAAGGCGACCGCCAAAAACCAGAGGATGCCAAAACACCGCAAAGCAGAAAAGGGTA GAAGGCGACAAAAAGCACAAGAAGAGTACGGGAGAGGCCGCGCCAAACAACACCTACAAACCAA GAACGAGCAACAACGAAATGAGGGGCAGCACAAACGCAGGGGGCGCTAGAACAAGAGGACCGGG CCGCAAACACTCCCAGACAAAGAAGGAGCGACGCAGAGTAAAAACGGAACACACACAAGAACAG CCTGAAAGGCAGCGCGAGAAAGCCACACGATAAAAAAGAGGAGAAAGACCAACGAACATAGCAG CGGAAAAGCAGGCCCCGAACCGTAAACCACCGAAGGGAGCAACGAGACAATAGGAACAAAAAAC CAGCAAGCAGGAAATAGCCAAAACCAGCCGAAGCAGGAACAGTCCCAAAACGCACACGAAAGCA CAACGCTGCCACCGGGAACACCACCAGGCCAGGCTAAAGGAAAAGAAACCGAAGGGCGGAAGTG AACAACGGGCACGCCACAAGAAAGACTAACCAAAGACAACAAAGAACGAAGGAATACAAACAAA AGACGAAGGAACGAAAGATACAGGAGGAACAACAAACAGCAAGAAGTAAGAAACCAGAAGGACG GCAGAACCAGTGCGGGCCCACCACCAAACAACAAGGCATACAAAACGGGAACAAGCCACAACCG ACTAGCGGCACAACAGCAAACAGCAAAGGATGGGCAAGGCACAAGCAACAGGCGGAGATAACGA CCACAGAGGCAAGCAGCGACGGTAGGAAGGCACCAACAGCAAGAAGCCCGTGCAACAACGCAAG GGCAAGGCGAAAAATGACCGGGAAGAACCCGCGACACGGGAGTGGAGAACAGACGACCCGCCGC ACAGACTAGAAGAAAAGAGACAGCAGAGACACCCTCACGCAAAGCAAAGACAGGAAACCAAATA GGGCCGAAACAACCCCCGCCACCCGGTAAAAGAAAGAGAGAACAACAAGGAAGATACCACCAAA AAC AAGAAC C AAC C C C AAT AAG AC AG G C AAGAAAAC AGAAAG C GAG TGC GAAAGAC AAC AC GAC AAAGCGGAGATAAACAACGACAAGGCACGAGGAGGAAATAAGGGAGGAACGCGACCGCAACAGA ACTGAGACGAAAGACCAAACCAGAACGCCGTACACCGGGGCAGGACAAGCGAAACAAGTGCAAG ACCGCGAAAACCAGCCCACAACTCGAGAAAGGAAAACCAGGACGAAGGCATAACACCGGAGGCG AAGAGGCAAAACGGTCAAGAAAAACAAAAAGGGAAAGAAGCCTAGCGAAGCAAGGGAAGAAAGC AAAAAGTCCACACACGCGGGGAAAAAGGACCGACTCGAAGGCAACAAGGGAAACGCGAACGATG ACCGAAAAAAGAAACCCGCAGGACAATACGCCAGCCAACCGGAACGGAAGAAACTAACGACAAC GAGAGGACACGAGAACCGTACAGGGCAGGCGCAAACCAAACCGCCATAAGCACCAGACGACGAA GGGGCAAAAGTGCGGAAACGAAACCAAAAGAGGCGAAATACAACCCAAAAACCGACCAACCACA CATCCAAGGAAGGGGGGAAAACGAAACGAGTAAGCAAAAAACCGGCAAGCACGCGGAATGAAAC GAAGAACACAGAAGGCGGCAGCTGACGCCAAAGCGGCAACAAAACAAACATCAACGGCAGGAAC GAGAGGGAGAAACATAACAACCCAAAAAGGAGACGAACAAAATCGCACCCAAACAGCGCCGAGGACAACATGAAAAGGCGAGCAAGCGGCACACGGGATACAAAAGAACCCAAAACGCGCCAAAAATC AAC C AAAGAGAAC GAG GAG G G C G GAG T C C AAAG C C GAG AC GAG AAC GAG GAGAAT AAGAAC AGA CAAAAAGCCACCGAAGCATCAACACAAAGACAGCACAAGGAGGCGGTCACCCGGCGAGAAAACA AAGGGAAAGATACACGCCCAAGGCAGAAAACCAAAAGCTAGCAGCGAAGCACGAAAACAAAACG AATCGCGCCCCAAAGACGAAAGCGAGAGACTAAGAAGAACGGAACAGCAGGAACAACGTAACAA GGAAGAGAAGGACAAACACGACTAACGGAGAAAAAGCAGGACCCAGAGAGTAAACGCCACAAAC ACAGAGGGCGACAGTAACAGCGCAAGACACGCAACAAACGACTGAACAAGCCCGCACCCAAAGG GGACCGTAGAGCAACCGGGCAAGAAGAAACAAAATAACGAAAAAACAAACAAAGCGGAAAAATA GAAAAAAAGCAAAGGGGGAGAAGGCGTGAAACCGAAAGAAGGAAGCACACCGCATAGCACAGGA C AAAG GAG AAAAAAC C AAT G GAG GAGAAAAC G GAAC GAG C AAAGAG TAG AC AAAG C AC AC AC C C CGGGCGGCAGTGAAAGGAACACAAAAAGACCCGACACCTCCACGCGCGGAAAGCCAGACAACCA AATCAGCAAACAACAGCAGGAGAAGGAAAATAGAAAAAGAACCAAGAAAACAAAGCCATCGAAA CGGGAAGCCCAGAAGAACAAACTGAAGAAGAAAAGCAGACACAAAAAAGGTAACAAAAGAAAAG GCCAACAGCAGGAGTCCCAACGACCCAACACCCCCGCGGACATAGCAGCGAAGGCAAGAAAGGG ACAAAATAGGAACGAACGACACACAAGGAGAACGTCAAAAAAGGGCGAGGCAAGAGCAACAATC CAAGGAACCGAGCGGAGAAAACGCAATAGACAAAGCACGAAACACAACAGCAAATCACCCAGAA ACGACCAAAGACAAGGGATGAGGAACACAAAAAAAGCCCCAAAGACTGCGAAAGGACAAGGGGA AGAACCAAAATAAAAGGGCAGAAACGCAAACCACCCCCTCCAAGAGAGGGAACACACACCAGGG AATCCGGGGAAAACGACGAAAACAGACGGCTAACAGGAGAAAAAAAGCGGCAGCAGACTCCCAG ACGAACAAAGACAAGACAAGAATGGAAAGGGAAAAGAAGAAGGAGCGCAATGAACAAGCGAACC AAGAC AGAAAC AAAT AC C C C G G C AAAC AAAAC AGAAC C C AG C T AAGAGAAGAAAGAC AG C AG C G GCCGAGTACAAAGGGGAACAACCAGAACCAACAATGGCCCAAAGCAAGCACCCAGGGACCCCTA AAAGAAACCCCACGACAGGGCAAAAGTAACCAAAGGCAGGACAGGAAACACCCGTAGACGAGAA ACCACAGGGGCAAAAAACTAAGCACAGCACGAACGAAGGAGGAAGGTGAGCCAACCACACGCGA GGGCCGCCCGTCACAACAAGAAAAAAGCAAACCCGGCCTAAACAAAGGAGGAACAACAGGCCAG CCTCAAAGAAACAAGGCCGACGCAAAACGATGAAAGGGCGGCGAGGCAGAGAGAGAAATCAGGA ACGCAGGCAGAGAGCGGGGGGCTAACGGAAAAAAAGCCAAGAACCGAGGCTACAAGGAAACAGC GAAGGAGCGAGCGCTAGACGAAGGAAGCGACAACCGCAACCGTCCCCAGCCAAACGAACACACG GAAAAC T GAC GAAC C GAG C C AC C AC AC C AAC AAG T C G C GAG C C AAAAC AC AAGAAC C AGAAAT A ACCGGAAACACACGACCGGGAAGAAATCAGAAGGAGGGACAAGGAGGACGGAAATACACGCGGG GGGAAAACCACGAGGCGATAACAGACCAAGCACGAACACCAAACCATCCAGAAGCAGAGGAGGC C G GAC G C C C AT AC C G C AAC GAG C C AGAGAAAAGAC C AAT GAGAAC AGAAAAC AAAGAC AC GAAA AGTCGACAGGAAGAAGCGGCAAAACAGACCTCAGAAAAGAGACAAAGCAAACCCCAACTGAGGG GGACGGGGGGAGGCCGGCACAGTAAGAACGCCAGACAAAGAACAAAAAAATCCGACCAACAACA CCCAACAACGGAAATAACGCACAACACCCCAGAAACAGAACATGCCGGCGAGGCCAAAAACACCACGCGATAACCAAACAGGAAAGGAAGAACCAAACTCACACGCCACAGCAAGAGAAAAGGAAATA AAAGCGACGAGCCACGGGCCAGACACTAAGCAACGACAAAAGCAAGCAAGACCGTGAAGGGACA GGAAGGAGAAACACAAGGTAACGCCAAAGAAAGAAAAACGAAAGAGTAAGGAAAGACAGAAAGG ACCCAACAGATACACAGGAAACGGGACCAAAGACAGGGTAAAAAGCAACACGACACAAGACCCA CATGCCCCGGGGCCAAGAGCAAACAGGGAATGCCCGAACAGCCGACCGGAAAAGAACCTGAACA CGCCACGAACACAGGGAGAAGCTCAAAAAACAAGGAGAAGCCAGGAAAGGTGGCGGAAAAACAC AGCGAAACGGCGAATCCACCACAACACCCGCCCAGCGACAAATGGCCGAAAGCGAGACAGAGAC GCGAGATAGGGCCACAACCAAGCGCCAACAGGCATACGAAAGCGCGAAAAAAAGAGCGAAGCTC GAAGAAAAAGCCACAGCAAACGAAGGTGGCAACGAGCCAGCCAACAAACGAAAATGCCAAAAGA CAAACCAACAACAACCGCTCGGCAGCGCAAACAGCCAAAGCAGAGCTGAGCCCGCCGGCGAAAA CACCGGGACCTGAAACGGCAAAACGCGAAAAGAAGGCATCCGAAGCGAAACGAAAAAGGCACCC CGTAGCCGAACACGCGGAAGGACCAGAAGCTAGAAGAGCACGACCCAAAAACACCACATTCGCA AAGAGACCTGCGGCCGCAGGCTAGGTGGAGGCTCAGTGATGATAAGTCTGCGATGGTGGATGCA TGTGTCATGGTCATAGCTGTTTCCTGTGTGAAATTGTTATCCGCTCAGAGGGCACAATCCTATT CCGCGCTATCCGACAATCTCCAAGACATTAGGTGGAGTTCAGTTCGGCGAGCGGAAATGGCTTA CGAACGGGGCGGAGATTTCCTGGAAGATGCCAGGAAGATACTTAACAGGGAAGTGAGAGGGCCG CGGCAAAGCCGTTTTTCCATAGGCTCCGCCCCCCTGACAAGCATCACGAAATCTGACGCTCAAA TCAGTGGTGGCGAAACCCGACAGGACTATAAAGATACCAGGCGTTTCCCCCTGGCGGCTCCCTC GTGCGCTCTCCTGTTCCTGCCTTTCGGTTTACCGGTGTCATTCCGCTGTTATGGCCGCGTTTGT CTCATTCCACGCCTGACACTCAGTTCCGGGTAGGCAGTTCGCTCCAAGCTGGACTGTATGCACG AACCCCCCGTTCAGTCCGACCGCTGCGCCTTATCCGGTAACTATCGTCTTGAGTCCAACCCGGA AAGACATGCAAAAGCACCACTGGCAGCAGCCACTGGTAATTGATTTAGAGGAGTTAGTCTTGAA GTCATGCGCCGGTTAAGGCTAAACTGAAAGGACAAGTTTTGGTGACTGCGCTCCTCCAAGCCAG TTACCTCGGTTCAAAGAGTTGGTAGCTCAGAGAACCTTCGAAAAACCGCCCTGCAAGGCGGTTT TTTCGTTTT C AGAG C AAGAGAT T AC G C G C AGAC C AAAAC GAT C T C AAGAAGAT CATCTTATTAA GTCTGACGCTCTATTCAACAAAGCCGCCGTCCATGGGTAGGGGGCTTCAAATCGTCCCCCCATA CGATATAAGTTGTTACTAGTGCTTGGATTCTCACCAATAAAAAACGCCCGGCGGCAACCGAGCG TTCTGAACAAATCCAGATGGAGTTCTGAGGTCATTACTGGATCTATCAACAGGAGTCCAAGCGA GCTCGATATCAAATTACGCCCCGCCCTGCCACTCATCGCAGTACTGTTGTAATTCATTAAGCATTCTGCCGACATGGAAGCCATCACAAACGGCATGATGAACCTGAATCGCCAGCGGCATCAGCACC TTGTCGCCTTGCGTATAATATTTGCCCATGGTGAAAACGGGGGCGAAGAAGTTGTCCATATTGG CCACGTTTAAATCAAAACTGGTGAAACTCACCCAGGGATTGGCTGAGACGAAAAACATATTCTC AATAAACCCTTTAGGGAAATAGGCCAGGTTTTCACCGTAACACGCCACATCTTGCGAATATATG TGTAGAAACTGCCGGAAATCGTCGTGGTATTCACTCCAGAGCGATGAAAACGTTTCAGTTTGCT CATGGAAAACGGTGTAACAAGGGTGAACACTATCCCATATCACCAGCTCACCGTCTTTCATTGCCATACGAAATTCCGGATGAGCATTCATCAGGCGGGCAAGAATGTGAATAAAGGCCGGATAAAAC TTGTGCTTATTTTTCTTTACGGTCTTTAAAAAGGCCGTAATATCCAGCTGAACGGTCTGGTTAT AGGTACATTGAGCAACTGACTGAAATGCCTCAAAATGTTCTTTACGATGCCATTGGGATATATC AACGGTGGTATATCCAGTGATTTTTTTCTCCATTTTAGCTTCCTTAGCTCCTGAAAATCTCGAT AACTCAAAAAATACGCCCGGTAGTGATCTTATTTCATTATGGTGAAAGTTGGAACCTCTTACGT G C C GAT C AAC G T C T C AT T GAT AC C T GAAAC AAAAC C C AT C G T AC G G C C AAG GAAG T C T C C AAT A ACTGTGATCCACCACAAGCGCCAGGGTTTTCCCAGTCACGACGTTGTAAAACGACGGCCAGTCA TGCATAATCCGCACGCATCTGGAATAAGGAAGTGCCATTCCGCCTGACCT

[0159] SEQ 2ACTGGTCTCAGCAATGCCAAACCACCGGCCAGGAAGAAGCCCTCAGCACAGGCCCAACAAGACA GGCGAATCGAGACGAAGAAGCAACGAACGGGCAATCGAGAGAAACAAAAAGAAAAAAGAACATG AGACGAAGCAACAGGAGCGAAAAAAGTGGCCAAAAGCAAAACCCCAACAAGCAATGAAGGAGAA CGAGAGCAAAAGAAAGACTGGCCGCGGCGACACGAGACGCGACCAGTGCCAGAGAGGGAGCCGA CAAGCGGACGTGCCCAAAAGACACACGCAAGAGAGAAATGGCCGAAAAAAGCAACAGCCAGACC GGTGCAAACCGGCAACGGGCGAAAGGACGATGCACACGGCCGACAGAAAACGGAGGACTACGGC AAGCGAAACACCGAGCAGCGACTCCGAAAACAAAGCGCGCAAGAGAACACTGGACAAAAGACCA GGAAAGCAAAGGAGTACAACAAGGGAGCCAAAAAAAGAAAACTAGGCAAAGGGGCAAGACCCAA ACCAACTGGGCAAAAAAGGGAAAAAGGAAAAGAATACGCGCAACCGGACGGAGCCAGACCCCTA CCGCGGACGCACGGAGGCACAGAACGTGACACAACAAACAAGCACGGCAAAGAGTAAAGGCAAA AAAAGAACGAGACACGGCTGCCGGAGGGGGAGCCACCGCAAAAACCTACAAGCACCAAAACACC GAAAGAGAAATAACCCCGAAACGGGAACAGCAGAGGAATGAGGAGACGGCGGGGAAGAAAAAAC AG T C AAAAAC AAAAGAAC C AC AAAG C C AC G TAG AAAAC GAAAAGAC AC AAAG C AC AG G T GAGAG AAGAACCAGCGCACGAAAGCCCTAGCGAAAAAGAGCAGGGCAGCCGAGCGTAAGCCGGACGGAA AAAAGCACACGAGATCAAAGACAGCCCGAAGCCACCGAAGCATACCAGCGCCAAGCACAAACAA AAGAAGTAAGAAACAAAAAAAGCGAAGAAAAAGATACAAAGGGGAAAGAAACAGAAAAAACATA CAACAAACAACCAGGGCCGCGGCCCATAAAACAGCGCAAACCAAGCAGAAGGGATAGCCGCGAC AGAAACCAAAGAGAACAATAGAAGAAAAACAAACAACAAAGAAAAATACAAACAAAGAGGAAAG C C AAC G C G GAT C C AAAGAAC AAG C C AAAGAC AC GAAGAT C C GAAAAAC C C C C AAC AC AAG GAGA AATAGACAGGCGAAACCACCAACAGCACCATACCGGCCAGAAAACCGAAGGGCAAAGGTCGCGA AAACGAACAAAGGGACAACAGCTAGACGAGCAAAACGGAAACAAAAAACCTAAGCAAACAACCA ACAAGACAGCAAAATAGAAGAAACCGGGCGACAGCGAAGGGATACAAGGACACAGCAGAGACAG GGCAACTCAACGAACGCCGAAAAAGAGGGCAGAATAACGAAGAGAAAGGGGCCGAAAACAACTA AC C AC C GAAC GAAAG C GAC AC C AGAAT AAC C AC GAC AAC AAC AAAGAAAAGAGAT AGAAAG G G G AAGAGAGAAACAAACGGCTCGCAAGGAGGCCGGACGCAGCAGCGGCTAGCAAAGCCAAAGCAAG ACAGCGCAGATGAAGGACAAACAGGGCAAGCAAACAAATAGCAGAAGGAAAAGACAAGCCCAAAAATGACACAGACCGCAACAAGCGACAACAGTACAGCGGACCGAACAAGCGCCAGAACATCGAAC AGAGAGAAGGGCACGAAACAAATACCGAAACCGGAGGGAACAGAGAAGAATAAACAACAGCGCA AAGAAAC GAG GAAC T GAG C C GAGAC AGAGAC GAAG C AAAGAC T C GAGAAC AC AAGAG C C C AAAA GGACCGTGACGAGAGGACAGGAACAAAGCGGGACTCACCAGAGAAGCAAGAGAAAACGAGACTG CAAAAGGGCACGAAGGAACGGACAAGTCAAAGAAACGCAAACAACCCGAAAAAATAGACAAAAC AAACGAAGAAACACAGAATCGACAAGGAGAAAAGCAGCGGAAACAATAAAAGAGACAAGGCAAA CAAGCCGGCATAGAGGGCACCACGAGAGCAACGAGGACTGGCAAAACCGGGCCCAAGAGAAAAA GATACGACAAAGGCAAAGGAAGAAAACCGATGCCAGGAAACGCCCAAACCAGGAGAAGTACCAA GAAG GAAAAAAAC GAG AG C C AAT AAC AGAC AAAC AAC GAGAGAAAAAC G C T AGAAAGAC AC C AG AAAGCGGAGAGCAATGCACAAAGAAAACAAGCACGGAAACACTGGGACAAAAGACCGAAGAAGC AG G GAC T AC C C C AC AAAAC C GAGAAAC G C C AAGAT AAAAC AAG C AC AC GAC C AAC AC C GAC AT C CAAGCAGAAAAAAGCACCGCGCCCGATACAAAAAACGACACGCAAAAAACAGGATAGCACAAGG GGCAGACCACAGGAACCGTGGCGAAGCGGCAGCGAGAAGGCGGCACTAAAAAGCAACAGCAGGA CAAGGACGCATAGAAGCGGAAGCGGAGGAAAGAGAAAGTCGAAGCCCCGGCAACCAACGAGGCA GATACGACAAAGCAAGCCACGAACGAACCGTCCGGACAAGCAGGAAAGCGACGAGCAGTAGGAC GAAAAACGCAAAGCAAAGCGACTCCAAAGCAAGAAAACGAGAACCAGGGCTGAAACCAACAGAG AC AAC AAAC AG C AG T C AC C AGAAC AAGAC AAAC AGAAAC AC C T AGAAAAC C G GAAC C GAG C AC C GAGGACTAAAAGACGAGGGCAGACCAAGAAAACATCGAGAAAACACAAAAAGAAAACGAGCCTG C GAAAC AGAAAC AG C C GAGAAAC GAC T AAAC G GAAC GAC C AG GAC GAAAAG GAG T AAAGAAAAA GAACCACCGGAGAGCAACTACCACAGGAAGAAGGACGAAAGACGGATCACGGAAGGACAGAGGG GAGAACCGGATGGAACAGAGAAAGAAGAGAACAAAAAATAGGCGAAAGGGAGAGCACGAACGAG CATAAGAGAGCGACGCAACGAGCCGACAAATGCGCACGGCGGCGCAAGAAGAAAACGGTGGGAA AACAGAGACAAAAACACAACCCTCGAAAACAGCCCGACACAGCACAAAAGTAAAGGGAAAGCGA GGAAAGGGAACACCTCGAGAAAACGGCGGAAAAGAAAACACCTAAAGACGACAAACAACCACGA AGGAACTAAAGAGGCAAGAGGAACGACCAAAAAGTAAGACAAAAAGGCGGGCAACAAAGGCGTC AACGCAGACACAAAAACAGCGGAGCCTGCAGAGAGGACGGCGAAGAACAAAGACTCCACAAGGG GCCCAGCGAGCACACAAGTCCACGAAAGAAGAAAAAGAGAAAGCCATCACACAACAGGACACGG AAAGAAAACCTAGACCGAGAAACAGCGGAAACAGCAGGTGAACCCAGAGGACACGAGGCAAAGA AGTAACGGGAACGCAACGAAGCAGCACAGCTGAAAGAAAGAAGGAGAAACCAGGGGACTAACGC ACCGCCAGAGCAGAAAGAAGAATGCACGAAAACACAGAACCAACCAGCACTCACCGGGGACCGA AGGACCGAAACGCATACAGAAGGAAAGCAACCAGGCGCGGCATGAACACAAAACGGGACAGCAC AGCGAGTAGGCCGCAAAACCGCAGAGCCCACAGATGGGAAAGCACGAAGCAACAGACCAACATA AAACAGAAAGGCGAAACACAGAAGCATCGAACAGCCACAGCAAACCAAAGGACATGCCCGCAGG GAGCAAGGCCGCGAGGAGTAAAAGAGCAGAAAAACAGGCGAAGGAGTAGGAGCAAACCAGCCAA GAGAAAGGAGTGCAAGGAAAAGAGCAACACAAGAAGAATACCAAAAGCGAACAACAACGACACGAGTGCAGCAAAAGAAGGGCCAAGACACAACTACAAGGACAAGAACAAGAGCGCAAGGGTCAGAA AACCCAACGACAACAGGCGAAGTACAGAACGAAACGACAGCCCACACCAGTCAAGGGAGAACCA ACAACCAGAAAACCTGGCGCAAACCAGCACCGAGAAGAAACATGGACAGAACGACGAGGGGAAA CCAAGCTAAACGACACGCACGGCACGGACGCAAATGGACCAAACAAGAGGACAAAGGCAGGATA ACCGGCAAAACCGAGACGGAAAAAAATGAACGAAACAGGCAAAGGGACGCCGGATGACCCAAAC CACCACAAGAAAACAAAGTCAGAAAACGCGAAAACGGGAAGAACGGTCACAGAAAGGAAAGAAC GCAAAGAAAATGAAACCAACGACACCGAGCGCAGAGCGTAAGCACGAAGGCAACACCAACCCAA C G T AC C AAGAGAAAC C GAAAC G C AC AAAC C T C AG GAAAG C C C C C GAC C AC AGAC G G C C T AAGAG AACAAGAGGCGAAACGAAGAGGTAACAGAAGCAGAACCCCGAACGGAAGCTGGAGAAGAAAAAC AGCAGACAACCGAATGCCAAACAGCAACACGACGACAGGAAATAAAAAGCCACACCCGGGAAAA CAGAACTGGCGAGACAGCACGGCGAAAAGGCCAGTACGAAAAGGACAAGCAAGGAACAAGCGTG GGGAACAGAGCAGAGAAACAAGCGAATGAAACACCACGAACGAAGCGCAAAAAGTAACGGAAGA AAGACAACAGCGAAAGCATAAAAACGGACAAGAGAGAGGCAACAAGTCCAACGGAGAAGAGAAC GCACGAGAAGTGACAAAAGGCAAGCGAAAAAGAAAGGGTGCAGAGACACAAAAGGACACCAGCG AATCACCCAAGGAAAGAGGACGGAACCGGATAGGCGGCCGACAACCAAACAAGAGAAGTGGCAA ACGACAACAAGAAAACGCGAAATGCGGAACCGAAGGGCCCAGGACGAAGGTACAAAAGAAAGAC AACACAACAACAGATCGCAAGGGCAGGCAGGGACGACAGCGCTCGCACCCCCGAGGAGACAAGA CCGACGTGAAAACCACGCCAGGGACACAAGCCCATCACCAACACGCCCAAAAAAGGCCAACCTA CAACCCACCCAAGAAGGCACCAAAAGTGGACGAAGGCAAAAACACACCCCGGAATACAAAGGAC AGCCGAAAGAAGGGGACATGCCAAAACCAAAAGACGGAAAGAAGGGTCGGAAACGCGACAGGCA AAAGAAAGCCTACGGAACCGAAAACAACACGGAGGAAATCGCACAACAAAACAGACGCCACAAG GCTACACGCGGAAGAAAGACCGCGAAAACATGCGAAAACAAAGACCGCACGGAAAAAATCGGAA AGAACGAAAGACAACGCGAAGCTCCAAACGGAAACAAAAGACCAGGGAAATCGAACAAAGAAGG AGACAGGGACACACTAGGAAAAAAGCCAGGAACAAGCCAAAGTCGAAAACAAACACGAACCGCA AAGGGGTGCGGAACAACAAAGACGCCCGCGGAAATAAAGGAACGGCACCAGCACGACACGGATA AAACCACGACAAAAAACAAGCCGAAATGACGCGGAAGGCGCCACAGAAACGCAATGGAGCAACG CAGCAGGCCCCGAAGAAGTCGGCCAGAAACGCGCACCACCGACAAATACGCGAACCAAAGACCA AGAGAAG C AAT C AAAC C AGAG GAAAC C AGAC C AC C AAAT GAAC GAAC AAG C AGAAAGAC AAAC A GCTAAACCACAAGACAGCGCCAGAGCAGAATACCAGAACCCAGCCGGGCCCGAAAAACTCCACA CCAGCCAAACAGCAACGGGCAGTAACGAAAACACCGAAACAACCAAACAATGAAAGAGCAGGAG GGAAACGCGGGAAATAGCAACCCGCCAACGCCGAAAGAAAAGTGCAGGGAAACCCAGGCCCGGG AAGAGGTAAACCAAGAAAAGCCAAAAAGGAACGCTAGAAGAGCGCAGAAGCCAGGGCGACAATT CACTAAGAGACCTGCGGCCGCAGGCTAGGTGGAGGCTCAGTGATGATAAGTCTGCGATGGTGGA TGCATGTGTCATGGTCATAGCTGTTTCCTGTGTGAAATTGTTATCCGCTCAGAGGGCACAATCC TATTCCGCGCTATCCGACAATCTCCAAGACATTAGGTGGAGTTCAGTTCGGCGAGCGGAAATGGCTTACGAACGGGGCGGAGATTTCCTGGAAGATGCCAGGAAGATACTTAACAGGGAAGTGAGAGG GCCGCGGCAAAGCCGTTTTTCCATAGGCTCCGCCCCCCTGACAAGCATCACGAAATCTGACGCT CAAATCAGTGGTGGCGAAACCCGACAGGACTATAAAGATACCAGGCGTTTCCCCCTGGCGGCTC CCTCGTGCGCTCTCCTGTTCCTGCCTTTCGGTTTACCGGTGTCATTCCGCTGTTATGGCCGCGT TTGTCTCATTCCACGCCTGACACTCAGTTCCGGGTAGGCAGTTCGCTCCAAGCTGGACTGTATG CACGAACCCCCCGTTCAGTCCGACCGCTGCGCCTTATCCGGTAACTATCGTCTTGAGTCCAACC CGGAAAGACATGCAAAAGCACCACTGGCAGCAGCCACTGGTAATTGATTTAGAGGAGTTAGTCT TGAAGTCATGCGCCGGTTAAGGCTAAACTGAAAGGACAAGTTTTGGTGACTGCGCTCCTCCAAG CCAGTTACCTCGGTTCAAAGAGTTGGTAGCTCAGAGAACCTTCGAAAAACCGCCCTGCAAGGCGGT T T T T TCGT T T T c AGAGC AAG AGAT T AC G C G C AGAC C AAAAC GAT C T C AAGAAGAT C AT C T T A TTAAGTCTGACGCTCTATTCAACAAAGCCGCCGTCCATGGGTAGGGGGCTTCAAATCGTCCCCC CATACGATATAAGTTGTTACTAGTGCTTGGATTCTCACCAATAAAAAACGCCCGGCGGCAACCG AGCGTTCTGAACAAATCCAGATGGAGTTCTGAGGTCATTACTGGATCTATCAACAGGAGTCCAA GCGAGCTCGATATCAAATTACGCCCCGCCCTGCCACTCATCGCAGTACTGTTGTAATTCATTAA GCATTCTGCCGACATGGAAGCCATCACAAACGGCATGATGAACCTGAATCGCCAGCGGCATCAG CACCTTGTCGCCTTGCGTATAATATTTGCCCATGGTGAAAACGGGGGCGAAGAAGTTGTCCATA TTGGCCACGTTTAAATCAAAACTGGTGAAACTCACCCAGGGATTGGCTGAGACGAAAAACATAT TCTCAATAAACCCTTTAGGGAAATAGGCCAGGTTTTCACCGTAACACGCCACATCTTGCGAATA TATGTGTAGAAACTGCCGGAAATCGTCGTGGTATTCACTCCAGAGCGATGAAAACGTTTCAGTT TGCTCATGGAAAACGGTGTAACAAGGGTGAACACTATCCCATATCACCAGCTCACCGTCTTTCA TTGCCATACGAAATTCCGGATGAGCATTCATCAGGCGGGCAAGAATGTGAATAAAGGCCGGATA AAACTTGTGCTTATTTTTCTTTACGGTCTTTAAAAAGGCCGTAATATCCAGCTGAACGGTCTGG TTATAGGTACATTGAGCAACTGACTGAAATGCCTCAAAATGTTCTTTACGATGCCATTGGGATA TATCAACGGTGGTATATCCAGTGATTTTTTTCTCCATTTTAGCTTCCTTAGCTCCTGAAAATCT CGATAACTCAAAAAATACGCCCGGTAGTGATCTTATTTCATTATGGTGAAAGTTGGAACCTCTT ACGTGCCGATCAACGTCTCATTGATACCTGAAACAAAACCCATCGTACGGCCAAGGAAGTCTCC AATAACTGTGATCCACCACAAGCGCCAGGGTTTTCCCAGTCACGACGTTGTAAAACGACGGCCA GTCATGCATAATCCGCACGCATCTGGAATAAGGAAGTGCCATTCCGCCTGACCT

[0160] SEQ 3ACTGGTCTCAACTATGCCACAAAAGAACCGGAAAACAACGCCTCAGCACACACAACAGGAACAA CGCCAATGAACGAAAGGGAACGAAACAAAGCGGATAAAACAACAAAGGCGCCGAACGAAAACTA AAAAGGACCCAGGCGCGAGCAAGGCGTGGCAAAAGGCGCAAAAACAAAAAAGGGTCGCCCAAAA AAGAACAACAGACGCAAATCCAAGACCACCGAGAGCAGAACGACCGTGGAACGAGAGCCGCAAG CGAGGACCAATAACACAACCCAAGCAACCCAAGCGGCGTAACAGGCGCACAAGAAACACACGAG C AT AAAAAAC GAG C GAAAAG C C AAAC C GAG T AAAC AC AC AAGAAAC AAAAC C AAAAC G T AG C ACCAGAAACCCAGAGGAAACCAGATAAGAAAAAGAGCCAACGCGGAGAAGCGTACCAAACCCAAAG AAGGACCAAAAAAGTAAAAACCACGGCAAACAGCAGGACGACTAGCGCAGGACCCCACAAACCA AAAGAGTAGGGCCCAAAAACGAGGACGCGGCACGTCAAACCAAAAGAACGACAACAAACAAATG GACAGAAAACGAGCGAAGCACGCGGGTAACAACAACCCAAAGAAGCGAAGGAAATACACAACAA ACAACCAACAGAGGACCATAAAAGAGCAAAGAAACGAAGCCGAAAATACGACAAGGGGAAAGAA GCCGAACAGATGAAGGGGAAGCGACCGGGCGACAAACATAAAACAAGACCAAAACCCCAGCGCA GATAGAGCGAGCAAAACAGAACCGAGAACATACACAGAACCAAAAGCGAGAACAGGAGTAAAAG AGAAC AC AGAG C AAC C AAC GAAT AC C AAG GAC AAC GAGAAC AAG GAAAAC T AC C GAC AGAAAC A AGAAACAAACCGCGTGCCACGAGGAGGAAACGAAAAACGGCATACCAACCCCAAGACACAAACG AGGACGTCGGAACCAGGCGCCACCACAAGAAGGCTACACGAGACACACGGGCACGAAGAGGATA CACAAAAAACCAAGAAAAAGAGGCCATGGACCAAAACAAAGAGGCGACACACAATGACCGCCAC ACGCAAACCAAACAACCATCACAAGCGCCGCCAGGGAAGAAACAACTACAACGAAACACACACA GGGAAAGAGATAAAGGACCAAAAGAAAAGCAACAGGAATCAAACACACCGAGCGGAGAAAGGGA AGTGCAACAGACAAGAACCGCCAGGCAACCTGCCGCCGCCAGCCAAGGAAACCAACAATAAACA CAGCAGGACCAAAAGACAGACGTCAAGAGGCCAAAAGCCCAAAAGGGCAATGGACCAAAAAAAC AAAAACCCCAAACGTACAACAACCGGAAAAAGAACAACAACGTGGCACAACACGGGCCGAAAAA CCAAACTGAGGGAGGACACCACGAAACCCAGAAATAAGAAAAAAGCCCGAAACGCAGAAAACTA GCAAGCGCAAAGAAGGAACAAAGAAGTGGACACAAAACAAAGCCCAAAAAACGATCGAAGGCAA CAAAAGAACAAAACCGAATGCAAAAGGCGAAGAAAGCGAAACAGAATGGAAAGCGCAAGAAACC AAGCAAAAAATCAACAGCACCACACAGACGAGACAAAATCCAAACCGGCGACAACGGAGAGCAA CATCGGAGCCAAGAAAGGACAAAACCAGAATGCACAAACCACACAAAGCCAAAAGAGCTGGCGA GCCGAAACAAAAAGCAGCCGGGTGAACCACAAGAGAAGAAAAAAACAAAATAACGCACAACGGA GAC G C C AAAG C AAC T C C GAAC AC AAGAC AAC AAC AGAC C AC C T AAAAAC C G C AGAC AGAGAG C G AACCAGTAGGGAAAGAAAGGGCACCCAACAACAGTGCCGAAAAAAGAAAGGACAGCAACACCTG GGCACCGGAGCAAAAGACGGAGACGATACGAAAACAAAACCCGCCGAGAGGACGTAACACCGAA AGAGAC GAAC AC C G C AAC T C AG C C C C C AC C G C C GAAAGAAAGAG GAT AAC GAAAAC G C GAC C C G CCAAGCCCCGTGGGGGAGAGCGGCCAAACCGGGCACACTACCAAAACGGACAAAAAACAAGAAA CGTAAAAGGGAAAGCCAGCGAGCCCACCAATGACCAAAAAAAGAACAGACAGCACAAATCAACG AGAAACCGCGCCCAAGCCAGAGTGCCAAAGGAAAAACCACGGCCGGCAACTCAAAAGGGCAGCC CACGCAAAAGAAAATGAAGAAAACCCCCCAAAACGGGGACCATGCACGCGAGAAAAAGCCGCAG AACCCATAAAAGAAAGACAAGAAGCAAAAAAGACTACGAGGAAGCCCCGGACAACAAAGGGGTA AAAAGAAGAAGAAGAAAGCCCACGGATAAAGCAAACAAAGGGGCCAAGAACGACTGGAACCGAG AGCGAGGGAAGAAAAAACTGCCACGCGGAGCAGAGGCAGAAACCAATAAAGAAAGGGCCAGAAA AGAAAGAAAGTGAACAGCAAGACAAGCACAGAGCACCATCAGAGACAAAACCACGCAAACAAAA AGTGACACCCACAACACAAGCCCGGAAGCGTAAGAGAAAAGGGAAGCAAACCACACGATAGGACAGAAAGAAACGGAGACACAAACTCAGAACAACGGGAGACGAGCCCGGCAATAGGAGAAGAGGAG GCGGGGGAAAAAAATAGACAAAGGAAGAGGGACGGAGGCAAATCAACCAAGCCCAAACAGAGCC GCAGGATGACAAGGGGCGCGCACCGACGGAGCAATAAAAGAGGACGACAAAAGGAGCAAAGATA CACAGAAAAGCAAGCCAAGAGAAGAATGGACACACCACAACCGCCCGGCAGGAATGAGAAAGAC AAACAACCAAGAAGGGGATAACAGCACGGCGACCCGACCACCCAGCTAAAAGAAAAAACAAGAC CACACACAAGTGACAGAGGAACAAACAACCGGCCCAGCTAGACCCACACCACGAACAGGACACA GGTCGCAAAAAAACCCACAAGAGACAGCAGTGCGAAGCAGCACGCGGGAGGGGCCGCCTAGAAA AGGCAACACAACGGCAACAACGTGGACGAACCACGGACGCCACCGAGCCCTAGACCCAAAAAAG C AAGAC AGAC AC AAT AAAAAAAC C AGAAAAAAGAAG C G C C AAT AC AAAC AC C C AGAGAAAAC AG GAAGCATAGCAAGACCAACACCGGGAAAAAAACATGGAGAAAACAGGCGCAGAGAGGAGAAGTC CAAAACGGAACGGAACCAGCGAGGAATAGGCACAAACGCCCGAAACAAGGACCATCCCAAGACC AAAGAAAGGAGCGCCAAATAAAGAGAGCGCACAAAAACAAGGGAAATACCCAGGCGAAAGGAGC ACACCGCCAATGGCGAACAAAGAAACCAACAAACAGAGTGCACCAGGGGCAGAAAAAAGGGCCA CCTAAAAAGCAGCACAAGACAACGAGCAGCTGACAGAAAAGGCAGGAACGGAAAGGGATCCGGG GGCAACGCAAACAAACGAGCGCTCAGAAAAAAACACCAAGAGAAAGACCCTGAAGCCAAAGAAA AGACAAGAACCCCATCCACGCGCACGGGACGAGCAGCAGGCGTCGAAAAAACGGGGCCAAGGGC AAGCGATGCCGAAAAAGCAACAGAAAGGAGAACATCCAGCAAGCAAGGGCAAGCAGGCGGGATG AC C GAAAAAAG C AGAC AAAGAC AC CAT C AC GAAGAAC GAAAGAAAC GAG C AAAAT AGAGAAC G G CACCAACACGGAACCCCATCCAAAACGGAACCGCACCGGGGCCACGTCCCCCCAACAGCGGCAA AGGAGAAAAATAGACGAGCGCAGCACCGACCAGCCGGATAAGAGAAAGAAAGGCGAACGGGGCC ACTGACGAAAGCGCCGGGCGACAACCACCATACAAACCAGAGAGCAGAAAGAGAAGGATGCGAA CCAGGACAGCGAGCGACAAAAGTCAAGAGACGGCAAAAAAGAACACACAGTAGGACACAAAGAC CGGCCAAACACAAGTAGCGAAAAAGCGAGACAGGGACACCAGTCAGGACCCGGGACAGAGGCAC GCGACGTCGACGAGAGGGCAACGCAGGACAACCCTAACCGACGCGCGAAGCCAAAGACGCCATA GAAGAG C AAAGAAC C C C AC GAAGAAAT C C C GAGAAAAAAC AGAC AGAC GAGAAAT AG C G C AAC A GGGACACACCCAAGGGGATAGGCAGAGGCGGCGGCGAGAAACGCGCTAGCAAAAGAGGCACACA GAAAGAAGAATAAACAACGGGGAAAGCACAAACAGGAATAGAACGAAAACAAAGAAGCAAACAA GATCGCCACCCCACAACAGCGGGCGGAACATAGCAAAGCCAAAGGAAACCCGGCAAGCTACCCA CGACAACAGCACGAGCGAAAGCTACCGCCGAAAGAGAAAGGCAACACAAGTCAAAGAACACGAA CAGACCCAGCAGAATGAACAACAAAGACCGCACAAGCAGCAGTACCGCAAACAAGCCAAACAAG AC AC AAT AGAAAAC AC C AC AAG G C AAGAAAC AAAT AAAAAC AC GAAAG C C AC AC G C AAAAAC TA CAGGGAACCACGCAAACCCAAACGAGTACAGCCAGCAAGCACGCAAGAAAAAGATCAGACAACA ACCAAAACAGAGAAAGGCTAGGGACCAAACAACCACGAGGCAAAACTAGGGCGGAACGGAGAAC GGAGACAAAGTAAGAGGCGGGAGAAAACGCAAAGCAACTACCCCAAGAACACACCAGGGAAACG ACTCGAACGAAACGACGCGAAAGAAAGCAGTGCCCAAACACCCCAGACACGGGGCCCATAAAACCAACGGACACACGAGAGGAGGATCAAAGCAGGAAACCAAGGAGAGGCAACTGAACGAAAGCAAG CAAACAAAAACGCGTACCCGGAAAAGAGAAAGGAACCAACAGTGAAACGAGAAGGGCAGGACCC AACGGATGAACGAACAACGAAAGAACGCAAACCGTAGAGGGCACAGGCGAGAGCCACGAGGATC GACACAAGCAACAAAGCAACACGCACTAGACACGCAGACAAAAGGGACAAAACGTACAACAAAG GAG GAAAAAG C C AAAC C G T AGAC C AGAGAGAAAC C C C AAC C C C GAG T GAG C GAG AC AAAC C AAA GACCCAAAGCTAAGCGGAGCGCAAAGAAACGCGAGACATGACCGAAACAAAAGCAAAAGGACAA AG T AAGAC AAAG C AC AC AAG C AAAC AAAAG T AAC GAAAC C AAGAC AC AAC AC C AC C AAT AG C C A GAGGAGGCCCCGGAAGGCAGACTCCAGCCCAAACGGACCGAACCCCACGATACAAGCGAGACGA CCAAAAGAACCACCTCGAAGCGCCGAAGGAGCACCAAACGGCTAGAGCGACCCCAAACACCAAC AGGAGATCCCGACGAGACACAAAAGAGGGCAAAATAAGGAAGAAGCCCGAACAGGAGGCAGCTA ACGAAGCGCAACCAACGCACAAGAAGTGGGAGAAGCCCCACGCAAAGACAAAGCTGCAGGCAAA GAAAGGCGAAACGCGGACTAGGACCCAAAACAACGAGAGGGAGGAGTAACAGGAAGGGCCACGA ACAAGCGGCCTGAAACGCCCAAAAGCAAACGAAAGCAATCAGGGAACAGAAGAAAAAACGCGGA AATGCCCACAACCACAAACACACGAACCAATCAAGACAAAACGGAGGCAGGAGAAGAATGCACC CGAGGCACAACCCCCACGCCCGTAAAAAACAAGACAGCGAGCAAAAGCACTAGAGAACCAAAAA GACCCCCGAGCACCTGGAGCCAACAAAACAACGAGCACGGCATACGGAAAAACAAAACGGAGAG GGCAAGTAAAGACAAAAGAGCGAGGAGAAAACCATAGAAGAGCCGAAAAGAAACAGCACGCATT CTTACAGAGACCTGCGGCCGCAGGCTAGGTGGAGGCTCAGTGATGATAAGTCTGCGATGGTGGA TGCATGTGTCATGGTCATAGCTGTTTCCTGTGTGAAATTGTTATCCGCTCAGAGGGCACAATCC TATTCCGCGCTATCCGACAATCTCCAAGACATTAGGTGGAGTTCAGTTCGGCGAGCGGAAATGG CTTACGAACGGGGCGGAGATTTCCTGGAAGATGCCAGGAAGATACTTAACAGGGAAGTGAGAGG GCCGCGGCAAAGCCGTTTTTCCATAGGCTCCGCCCCCCTGACAAGCATCACGAAATCTGACGCT CAAATCAGTGGTGGCGAAACCCGACAGGACTATAAAGATACCAGGCGTTTCCCCCTGGCGGCTC CCTCGTGCGCTCTCCTGTTCCTGCCTTTCGGTTTACCGGTGTCATTCCGCTGTTATGGCCGCGT TTGTCTCATTCCACGCCTGACACTCAGTTCCGGGTAGGCAGTTCGCTCCAAGCTGGACTGTATG CACGAACCCCCCGTTCAGTCCGACCGCTGCGCCTTATCCGGTAACTATCGTCTTGAGTCCAACC CGGAAAGACATGCAAAAGCACCACTGGCAGCAGCCACTGGTAATTGATTTAGAGGAGTTAGTCT TGAAGTCATGCGCCGGTTAAGGCTAAACTGAAAGGACAAGTTTTGGTGACTGCGCTCCTCCAAG CCAGTTACCTCGGTTCAAAGAGTTGGTAGCTCAGAGAACCTTCGAAAAACCGCCCTGCAAGGCG CTTTTTTCCTTTTc AGAG C AAG AGAT T AC G C G C AGAC C AAAAC GAT C T C AAGAAGAT C AT C T T A TTAAGTCTGACGCTCTATTCAACAAAGCCGCCGTCCATGGGTAGGGGGCTTCAAATCGTCCCCC CATACGATATAAGTTGTTACTAGTGCTTGGATTCTCACCAATAAAAAACGCCCGGCGGCAACCG AGCGTTCTGAACAAATCCAGATGGAGTTCTGAGGTCATTACTGGATCTATCAACAGGAGTCCAA GCGAGCTCGATATCAAATTACGCCCCGCCCTGCCACTCATCGCAGTACTGTTGTAATTCATTAA GCATTCTGCCGACATGGAAGCCATCACAAACGGCATGATGAACCTGAATCGCCAGCGGCATCAGCACCTTGTCGCCTTGCGTATAATATTTGCCCATGGTGAAAACGGGGGCGAAGAAGTTGTCCATA TTGGCCACGTTTAAATCAAAACTGGTGAAACTCACCCAGGGATTGGCTGAGACGAAAAACATAT TCTCAATAAACCCTTTAGGGAAATAGGCCAGGTTTTCACCGTAACACGCCACATCTTGCGAATA TATGTGTAGAAACTGCCGGAAATCGTCGTGGTATTCACTCCAGAGCGATGAAAACGTTTCAGTT TGCTCATGGAAAACGGTGTAACAAGGGTGAACACTATCCCATATCACCAGCTCACCGTCTTTCA TTGCCATACGAAATTCCGGATGAGCATTCATCAGGCGGGCAAGAATGTGAATAAAGGCCGGATA AAACTTGTGCTTATTTTTCTTTACGGTCTTTAAAAAGGCCGTAATATCCAGCTGAACGGTCTGG TTATAGGTACATTGAGCAACTGACTGAAATGCCTCAAAATGTTCTTTACGATGCCATTGGGATA TATCAACGGTGGTATATCCAGTGATTTTTTTCTCCATTTTAGCTTCCTTAGCTCCTGAAAATCT CGATAACTCAAAAAATACGCCCGGTAGTGATCTTATTTCATTATGGTGAAAGTTGGAACCTCTT ACGTGCCGATCAACGTCTCATTGATACCTGAAACAAAACCCATCGTACGGCCAAGGAAGTCTCC AATAACTGTGATCCACCACAAGCGCCAGGGTTTTCCCAGTCACGACGTTGTAAAACGACGGCCA GTCATGCATAATCCGCACGCATCTGGAATAAGGAAGTGCCATTCCGCCTGACCT

[0161] SEQ 4ACTGGTCTCATTACTGCCACACACGAAACGAAAAAAGCGACCTCAGCCACACCAGGGAACGGGC GAAAGATACCCGACAAAGGCACGAAAGAGACAAATGAGGGGACAGAAAGGCGGCAGCAAGGGTC AAGGGCAACGGGCCAGAAAGCGAAGGTCGCGCGACAAGAAGCGCACGGGAAACGTGCCACCACC AAAGGGAAAAAAGAGCAATAAAGAAACCAAGAGAAGCGGGCGCCAATAGAAAAGCCAAGACGAG ACACGCCAACTACAACGAGAAGAAAACAGGCAGGAAAATCAAGCCACGAGAACGCAGAAAAAAC CATGAGGAAAGGAAAAGAAAAAACGGGGAATAAAAGAACCAGAAAGGAGACACAGGGATCCAAA ACCCGGGAGGACAAGCACCAAATAACACCACCACAAAGGAAACAGAAACATAGCACCCAAAAGA CGCAAGCACAGAAGTAGACAACAAGCCCAAACACCGACCCCATAAACAGGCCAGCCACCACCAA ACAAAATAAGAAGGAAACAAAACAGCAAAGCGCATACGCCACAGACCCAAACGGAGGAAAGATG GAAAC AAAAAC AGAG GAG AG C G GAAAT C AC AAAAC GAG C AGAC C C G G C C GAGAC T C C AAC GAAG CACCGAAACACGAGAACATACAAGAGAGAACAACCGAAGAAAGGGGTAAACGGAGGCAGAGAAA AAGAG C GAAG T AC C C AGAAAC G AAC C AC C GAG C G C C C AT AAG C AAAC AAAC GAC C C AAAC AC C C CATAAAAACAAAGCAAGAAAGGAAGCAAAGTACCAGAACGGCAACGCGAGGCGACAAGTGCACG CGCGAACCAGAACGCCAACCCGTAGAGCGAGGCACGAAGAAGAAGGGGGATCAGAACACGACCA GAGAAGAACAGCAATACAGACCAGCGGGCAAGGACCAAAACGTCGAGAAGGCAGGCGGCCGAAC AGACCCTGCGCAACACCACAACGGCAACGAGAAATCGGGAAAGAAAGAAGAGACGCCGAGACTA ACCGCGAGCAACAGACGAAACAGAGGTAACAAAGGCCCGCGAGGACAAGAAGCCTCGACACGGG ACAAACCAAAGGCCAGAGTCGCCAAAACCCACGACCAGGAAACGACTAAGCCACGACAGGGACA C C AAC AAAGAT C C AAAAAC C GAAAC AAAAC AAG GAG C C T C AC AAAG GAAAAAC AC AAC C GAGAA AATAGAAAGACAACACAAGGGGGGGAGCGATAACGAAACCGCCCCAGGCAACGACCGATGAAAG AAAAACAGCAAAAGCGGAAAAGTGACCGAGGGCCCGAGAACAAGCCCAACTGAACGACCAAAGCAACGAGGAAGGGCCTACACACGAGCCGACGAAACACGCCAACTGAAAACGCAGGAGCGACCACC GAGCAATAACAAACCGAACCAGAGAGGCGGAACATCCAGCAGAAAAGACACGGACACGAAGATC AGCAAAAAAAGGAAGAGGGGAGCGAATCCGACAGGGGACAACAGCCCGGCGCCATAGAAACAGG AAACCGCCAAGAAGCACATAAACCAAGACCCCACACCCCGCAAAGATAGAGCGGGGAAACAGCG AC AAAC AAC AT G G C GAAAAC AAGAAAC AAC GAG AAAAAT AC GAAAC GAAAG GAGAAC AAGAAAA AATGAAGGGAAAAAGGCCAACCCGCGCCAATCCGCCGGAACAGCAGCCAGCACCGAAGTAACAG GAC AC GAGAAC AAAG G C GAAG G T AAAC GAC AAC GAC C AC AC GAGAAAAC AT AAC AGAAAC GAC C CGAACACGAGGAGGTAAAAGAAGAGAGCAAAAAACCAGAGCCTGAGCCACACCACGAGACGGCG GACCGATGGCACGAGAAAAGCAAAACGAAAGCCATAAAACAAAAGAAAACGCCCCAACGGACTA GAGCAGAAAACAGCCAGGCAGAGAACTGGAAGAAAAACACGGAGGAGCCACGCATAACCAAGAG GGCAAAAAACGGCAGAGGTAGAGAGCGGGGACCGGAGAAAAAGAAGTGAGAAAGCAGGGAAAAC CAAACAGAGATAAAAAGGGACCGAAACAACGCGACCAGTAAAAGCAAAAAGAAGAAACAGCGAC AG TAG AC GAC AG GAGAAAAAC AAAAC C GAG T C AGAAAAAAGAGAC AGAGAG C C C GAC C T AAAAC GAACCGAAAAACCCAAGCAGAATAGAGAGCGGAGCCAGCAAAAACAAGAATGACGGCAAGACAA CAGCCACGACAAGCTCCACAACGCCGACACAGCCACAACGCATCGGGAACGACAAGCCAAACAC AAGAACTGGACACGGGACCGACAAGAGAAGAGACTACCGCAAACCCCAACGGCAGCAAGCCGTG CGACCGAAGAGACGCAACACGGGCAGTGCGACGGGGCGGAACAACACGGCAAGATAAACGGGCA CAGACGGAACGAAAACGCTAAACGCCAACACGCAGCCCAAAGGACATCGAGCAGAGAACACAGA AAAAAAGGCATAAAAACGCCACCAACAGCCAGAAGGCCTAGAAAAGCACAGACAGAAGCGGACA GCTAGGAGAACCCAGGCACGAAAACCAGGGTCGAGAGGAAAGGGGGGCGAAGAGAGGGTAAAGG AGAACCAGGACCAACCCAAAAATCCCAGCCGACAACGAGCAACAGAGAGCTACCCGAACGCCGG C AAAC GAC C AAAAG TAG C AAG C AC AC AC AAC AAAAAC AC AGAT C CAAGAAGAAC AAAAC AG C C G GAAGAATCGAAAAAGCCGCCCGCAGCCCACGAGGTACAACACGACAAACCAAGCAAGCGAACTA GACAGGGAACACAAAAACAAAGAGAGTCACCGCGAAAACAACGCAACAAAGGGATGGGACGAAA CCCGGACAGAGACGAGCCTAAAAACAACGGGGGCGAACACGAACAATGCCCCACGAGAACAGCA CACAAGGCAATGCAGGAAGCACAAAAAAGAACCCCCAATACAAAAAACAACAGCAGCGGCGGAC CGTAAAAGAGAACCCGGCAAAAGCGCAGGCTAGCGAAAGAACCCGAACGAGAGGGCAATCGAAC AAGAACCAAAAAGCGACGGGAGTAGCCAAGCAGACGAGAGGAAAAGCAGCTAAGCCACCGAGAA CACGGCACAGGGAGTAAAGAGACAGCCGCCGACCCCAAAACCTGAAGAACAACAAAAGCAGAGA GAAGCGTAGCGCCAAAGGGCCAGCCCGCCAACCCTAGGAAAACCGAAAAAAGGAGAACGCGGTC AAAAC GAAGAGAC AG C C C AC AC AAAG T C AGAG G GAAAAAAC AAC AGAGAAGAGAT AC C AAC G C G ACGAAAAGACGACGGAAGTGACCAGAAGGCAAACAGGCGAGCCGGATAACCCAGCCGACCAAGA CAACAAGCGATGGAAAGCCGCAAGAAGAAAAGACCCACTAAAGAACGAGAACAACGAGAGCAGC CCTCCGCCAACAACACGAGGACACAAAGACTCAAAGCGGGGGCCAAGCAGAAGCACCATGAGACACGAGCAGGAGAAAAGCCAAAATCGAGAGAGGCCACAGGGAAGAAAAGGATAGGGCACACAGAAAGCAAGAACAAAACTGAAGGGACGACAAGGCAGAACCAAACGTACCCAACCGCAGAAAAAAACG CCGCCGTAAGCAGAGAAGGCGCACGACAAAGGCATAACAAGGAACGGCAGAGCCGGACAGAATC GCGACACGGAAACGAGCGCGAAGGGATCAACACGGCGCCAGACAAACGGGAAAGTAACGAAAAG GAAAGAACAGCAACACCATGCCCAAGCCCACGCCCGCGCAGACAAGTCAAAAAGAGAGGAGCAG AGCACCGAAATAAAGGCCACCCCCACCCACAAAGGGCATACAAACCGAACAAACAAAAAGAGGC CATGCGAGAAACAAAACGAGAGAAAGAGAATCAAAGGAACAGAAAGGCCAGCAAAAGATCGGAA ACACCCACAGAGACGCGAAAAATCGCCACAAACCAGGGAAGAAACAGCCGTACCAGACAAAGCA AACACAAAAAACCATGAAACGAAAGGCCAACCCGAAAACACATAAAAAGAGACAGAACGAGGGG GAAGAATGGCCAGCAGGGACGAAAGGAACGAAACTAGAAACGGAGCGACGAGCACACGCCAATA GAAAAGACCAAACCACAAAGCGCCAATAGGCCGGGAACCAAAAAACAAGGGGCATACAACAAGA ACCAGAAGCCAAGACAAATCGGGAACAGAAAAAGCGAGCAAGAAAATCGGAAAGAACCAACCAA CGGAGGGCACTGGCAAACAAACAGAAAAGAAACACCACTCACGAGGCACAACGGCCAACAAAAA CATAAGAAGGAGAACAGAAGCAACCAAAGATGAAGCGCACAACACCGCAGACCGACGATAGACA GAAAGAGCCAAGCCCGAAGGAGTGAAAAAGGACAAAGGCGCGGCGCGGAATAACAAGCCACACC AGGACAGAGCAGAATAGGCGAAGAGAAAACAACAACAGACGATGCACCCAAGACACAAACCCAG AACGACTACGGGGCCACAAAGCAAGCAAAAAGCGTAGCGCGCACCGACAACAGAGCAAGAGATG GGCGACGAGGACAGAAAAGAGAAGCGTGCGACGCCGAAGAAGAGACAGACAAGATAACCCGAAC CAAAAGCCCCAAAAAGCCTCGGGCCGCGAAGGCCGACAACGAGAAGTCAGACCAAGAGGGGACA GAAAGAAAGCTGACCCGGCGAAACCCACGAGAGAACACTACGCAGACAACAGACGAAGGGAGCC AGTAGACGAACAGGGGGCAGGAACAAAAGCTAAACAAGCAGACGCGAAAGACAAGAACTAAAAG GAACCCAGCCGGAAAAGGGAAGTCAAGAAAAAGAAAAACAGAAAAAAGAATGAGCCCAGACAAA GAG C GAG C C G G GAG T AGAAGAAC C AAC GAGAG GAG C AAC AC C T AC AGAAAGAAAC G C AC GAAAC ACGGGCTGCGAAACGGACGACAAACAAAAAAGGATAGACCAGCCCCGCGCAACCAGAGCGGATA CGGCCCAAAAGGAGAAACCGCGAGGGTAAGCAACGAAGCGCACGAGAAGGACACTGAAGCCCCC C C GAAAAC C AAC C AC C AC T GAC C AC GAAAAAAAG C AAAG C C GAC C C T AGAAAAC AAC G C AGAC G ACAGCGGAGATGGGACCACGCCAAGAACACACAGACAATCGAAAAAAACAAGGCAAGAGGAGAA GAT GAC AAAAAC AGAAAAGAG G C AC G C AAC T AAGAAC AGAC AAAAGAAC GAC GAC AAC T GAGAA AACCGCCAGCGAAGGAACAGGCTCCACCCGCACGAGGAAACCAGCGAAAATAGGCGAAACACAA GAGACGACGGAGGATAGAGCCAAGACGCGCGAGAGCAGGAAGTAAACAACAAGCGAAAAAAAGC AAACAATAGGGGCGAAAACGAACAAGAGGGCCAGTGGAGCACCGGAGGAGGACCACAGCAAATG ACGCAGCAAAACACCGAGGCGAAACATACCCCGGAAGAGAAAGCACAACGCGAGTAAAAACCCA ACCACCAACCAGACGAAGTAACAACCCGACACCACAACGAGGAACGTAAAAAAAGCCAGGCGGG GCAGAAAAAATCGACAAAAACAAAAAAACCCCACAAGCTCCCCCGCAAGCAAAAAAGCCACGCG CATAAGAACAAACCCAAACCACACGAGGGGTAAAGAGGAAAAAACAAACCCGAGAACGTACCGC AACAGCCAACACACCCAACGAATAAACGGACCAAAAAGAGGAACACACGATGGGAGGCCAAACAGAACGACAGGCCGATCGCAAGACGAACACGGCAGAAGCCCAATAAGCAGCAAAAAAACAAACGG CCAGAATAAACGAGGGGAACGAGGCAGAGAACCCTAGAAGAGCCAAGAAGCGACAAAACGCATT CCAGAAGAGACCTGCGGCCGCAGGCTAGGTGGAGGCTCAGTGATGATAAGTCTGCGATGGTGGA TGCATGTGTCATGGTCATAGCTGTTTCCTGTGTGAAATTGTTATCCGCTCAGAGGGCACAATCC TATTCCGCGCTATCCGACAATCTCCAAGACATTAGGTGGAGTTCAGTTCGGCGAGCGGAAATGG CTTACGAACGGGGCGGAGATTTCCTGGAAGATGCCAGGAAGATACTTAACAGGGAAGTGAGAGG GCCGCGGCAAAGCCGTTTTTCCATAGGCTCCGCCCCCCTGACAAGCATCACGAAATCTGACGCT CAAATCAGTGGTGGCGAAACCCGACAGGACTATAAAGATACCAGGCGTTTCCCCCTGGCGGCTC CCTCGTGCGCTCTCCTGTTCCTGCCTTTCGGTTTACCGGTGTCATTCCGCTGTTATGGCCGCGT TTGTCTCATTCCACGCCTGACACTCAGTTCCGGGTAGGCAGTTCGCTCCAAGCTGGACTGTATG CACGAACCCCCCGTTCAGTCCGACCGCTGCGCCTTATCCGGTAACTATCGTCTTGAGTCCAACC CGGAAAGACATGCAAAAGCACCACTGGCAGCAGCCACTGGTAATTGATTTAGAGGAGTTAGTCT TGAAGTCATGCGCCGGTTAAGGCTAAACTGAAAGGACAAGTTTTGGTGACTGCGCTCCTCCAAG CCAGTTACCTCGGTTCAAAGAGTTGGTAGCTCAGAGAACCTTCGAAAAACCGCCCTGCAAGGCGGT T T T T TCGT T T T c AGAGC AAG AGAT T AC G C G C AGAC C AAAAC GAT C T C AAGAAGAT C AT C T T A TTAAGTCTGACGCTCTATTCAACAAAGCCGCCGTCCATGGGTAGGGGGCTTCAAATCGTCCCCC CATACGATATAAGTTGTTACTAGTGCTTGGATTCTCACCAATAAAAAACGCCCGGCGGCAACCG AGCGTTCTGAACAAATCCAGATGGAGTTCTGAGGTCATTACTGGATCTATCAACAGGAGTCCAA GCGAGCTCGATATCAAATTACGCCCCGCCCTGCCACTCATCGCAGTACTGTTGTAATTCATTAA GCATTCTGCCGACATGGAAGCCATCACAAACGGCATGATGAACCTGAATCGCCAGCGGCATCAG CACCTTGTCGCCTTGCGTATAATATTTGCCCATGGTGAAAACGGGGGCGAAGAAGTTGTCCATA TTGGCCACGTTTAAATCAAAACTGGTGAAACTCACCCAGGGATTGGCTGAGACGAAAAACATAT TCTCAATAAACCCTTTAGGGAAATAGGCCAGGTTTTCACCGTAACACGCCACATCTTGCGAATA TATGTGTAGAAACTGCCGGAAATCGTCGTGGTATTCACTCCAGAGCGATGAAAACGTTTCAGTT TGCTCATGGAAAACGGTGTAACAAGGGTGAACACTATCCCATATCACCAGCTCACCGTCTTTCA TTGCCATACGAAATTCCGGATGAGCATTCATCAGGCGGGCAAGAATGTGAATAAAGGCCGGATA AAACTTGTGCTTATTTTTCTTTACGGTCTTTAAAAAGGCCGTAATATCCAGCTGAACGGTCTGG TTATAGGTACATTGAGCAACTGACTGAAATGCCTCAAAATGTTCTTTACGATGCCATTGGGATA TATCAACGGTGGTATATCCAGTGATTTTTTTCTCCATTTTAGCTTCCTTAGCTCCTGAAAATCT CGATAACTCAAAAAATACGCCCGGTAGTGATCTTATTTCATTATGGTGAAAGTTGGAACCTCTT ACGTGCCGATCAACGTCTCATTGATACCTGAAACAAAACCCATCGTACGGCCAAGGAAGTCTCC AATAACTGTGATCCACCACAAGCGCCAGGGTTTTCCCAGTCACGACGTTGTAAAACGACGGCCAGTCATGCATAATCCGCACGCATCTGGAATAAGGAAGTGCCATTCCGCCTGACCT

[0162] SEQ 5CAGAGCGGCCGCAGGCTAGGTGGAGGCTCAGTGATGATAAGTCTGCGATGGTGGATGCATGTGT CATGGTCATAGCTGTTTCCTGTGTGAAATTGTTATCCGCTCAGAGGGCACAATCCTATTCCGCG CTATCCGACAATCTCCAAGACATTAGGTGGAGTTCAGTTCGGCGAGCGGAAATGGCTTACGAAC GGGGCGGAGATTTCCTGGAAGATGCCAGGAAGATACTTAACAGGGAAGTGAGAGGGCCGCGGCA AAGCCGTTTTTCCATAGGCTCCGCCCCCCTGACAAGCATCACGAAATCTGACGCTCAAATCAGT GGTGGCGAAACCCGACAGGACTATAAAGATACCAGGCGTTTCCCCCTGGCGGCTCCCTCGTGCG CTCTCCTGTTCCTGCCTTTCGGTTTACCGGTGTCATTCCGCTGTTATGGCCGCGTTTGTCTCAT TCCACGCCTGACACTCAGTTCCGGGTAGGCAGTTCGCTCCAAGCTGGACTGTATGCACGAACCC CCCGTTCAGTCCGACCGCTGCGCCTTATCCGGTAACTATCGTCTTGAGTCCAACCCGGAAAGAC ATGCAAAAGCACCACTGGCAGCAGCCACTGGTAATTGATTTAGAGGAGTTAGTCTTGAAGTCAT GCGCCGGTTAAGGCTAAACTGAAAGGACAAGTTTTGGTGACTGCGCTCCTCCAAGCCAGTTACC TCGGTTCAAAGAGTTGGTAGCTCAGAGAACCTTCGAAAAACCGCCCTGCAAGGCGGTTTTTTCG T T T T C AGAG C AAGAGAT T AC G C G C AGAC C AAAAC GAT C T C AAGAAGAT C AT C T T AT T AAG T C T G ACGCTCTATTCAACAAAGCCGCCGTCCCGTCAAGTCAGCGTAAATGGGTAGGGGGCTTCAAATC GTCCGCTCTGC GAG T G T TAG AAG C AAT T AAG AAAT T C T GAT T AGAAAAAC T C AT C GAG CAT C AA AT GAAAC T G C AAT TTATTCATAT C AG GAT TAT C AAT AC CATATTTTT GAAAAAG CCGTTTCTGT AATGAAGGAGAAAACTCACCGAGGCAGTTCCATAGGATGGCAAGATCCTGGTATCGGTCTGCGA T T C C GAC T C G T C C AAC AT C AAT AC AAC C T AT T AAT T T C C C C T C G T C AAAAAT AAG G T T AT C AAG TGAGAAATCACCATGAGTGACGACTGAATCCGGTGAGAATGGCAAAAGCTTATGCATTTCTTTC CAGACTTGTTCAACAGGCCAGCCATTACGCTCGTCATCAAAATCACTCGCATCAACCAAACCGT TATTCATTCGTGATTGCGCCTGAGCGAGACGAAATACGCGATCGCTGTTAAAAGGACAATTACA AACAGGAATCGAATGCAACCGGCGCAGGAACACTGCCAGCGCATCAACAATATTTTCACCTGAA TCAGGATATTCTTCTAATACCTGGAATGCTGTTTTCCCGGGGATCGCAGTGGTGAGTAACCATG CATCATCAGGAGTACGGATAAAATGCTTGATGGTCGGAAGAGGCATAAATTCCGTCAGCCAGTT T AG T C T GAC CATCTCATCTG T AAC AT C AT T G G C AAC GCTACCTTTGCCATGTTT C AGAAAC AAC TCTGGCGCATCGGGCTTCCCATACAATCGATAGATTGTCGCACCTGATTGCCCGACATTATCGC GAGCCCATTTATACCCATATAAATCAGCATCCATGTTGGAATTTAATCGCGGCCTCGAGCAAGA CGTTTCCCGTTGAATATGGCTCATAACACCCCTTGTATTACTGTTTATGTAAGCAGACAGTTTT ATTGTTCATGATGATATATTTTTATCTTGTG C AAT G T AAC AT C AGAGAT T T T GAGAC AC AAC G T GGCTTTCCCCCGCCGCTCTAGAACTAGTGGATCCAAATAAAACGAAAGGCTCAGTCGAAAGACT GGGCCTTTCGTTTTATCTGTTGTTTGTCGCATTATACGAGACGTCCAGGTTGGGATACCTGAAA CAAAACCCATCGTACGGCCAAGGAAGTCTCCAATAACTGTGATCCACCACAAGCGCCAGGGTTT TCCCAGTCACGACGTTGTAAAACGACGGCCAGTCATGCATAATCCGCACGCATCTGGAATAAGG AAGTGCCATTCCGCCTGACCTTGCCGGGAGCAGAAAGAACGAAAGAACCTCAGCCAACCGAAAC AGGCCGCGAGCCCTGAAAAAGCAGGGCAAAGGAGAGCCCGCTACAACCAAAACGGAAAAAAGAGGCAAGTACCCGAGCAGAGGAGCAAAAACGCAACTAAGGAGGAAGGGACCGAAACAACGAGGTAACGCAAGAAGCAGAAGCGAGGGCACATAAAACCCCACAAGACAAGCCCGGAAAGTACAAAAAGCG AAAAAAAGGAAGCCCAATAAAAGACAACGGGAGACGCAACAAAGATCACAGAGCCAGACAACGA AAAGAAAAATAGCGCCGGAACAAAAAAAGGCGAGAACTGAACCCAAGAACCACAGAAGCACAGG ATGAAAACACAGGACCACGGCAACGCAGCTGAAAAAAACAAAAACGCGAGAAAACAATAGAAAACCCAAAACAGACCCGGGCAGATAGAAAAGAACAACACGAAAAACCCAGCTAGAAACAACAAGGG AGGGCACAAAAAGTAAAACCCAAGAGAGAAGGAAGAAAAAGTGCAAGCCCCCCGACCGCCCACA AAAAATCAGAAACAACAAACAGGGCACCAGGAATGAGCAAGCGGAAGAAAAGGACCAAAAATAG ACCGGAGAACAACCGGAAACGGCCATAACCGAAACCACGAGGCCAAACAGAAATGAGGCGCACAAAAAAGACGAGGCCACCTGAGCAGAAGCCGCCCCGACGAGAAACATAGGAAGGGCAAGGGACCAGGAGAACAATAAAAGACAGCGGCCGACGAGGCAGGCCTAGGCAGACAACAAAGCGCGCAAACAA ATCCAAGGCACCCCGAACCCGCAGAGGCCTACGAGGGCCAAAACAAAAGCCAAGCGGTGCCAAA AGAGAAACAACGAAGGGGGGGTCCGCCGAAAGAGAGAACCACCAAAACATAAACAAGAGCGCCAGACCCAGCAACCATCAGCCACACCGGACAGCAGAAGCAAAATCCACAGAAAAGAGAAACGCAACCAGAATAAAGCAAAACCGCCACACGAAGAGAAGTAACAAAGAACCCCACAACGGGCAGCGGTCGGGAGCGAAGGAGAACACGACGACGGTGCGCACAACAAACAACAAGCACAGCGCTAGGGCCGACCAGGGAGAAGCAAGGAACTAAAAGGCGACCGCCAAAAACCAGAGGATGCCAAAACACCGCAAAGCAGAAAAGGGTAGAAGGCGACAAAAAGCACAAGAAGAGTACGGGAGAGGCCGCGCCAAACAACACCTACAAACCAAGAACGAGCAACAACGAAATGAGGGGCAGCACAAACGCAGGGGGCGCTAGAACA AGAGGACCGGGCCGCAAACACTCCCAGACAAAGAAGGAGCGACGCAGAGTAAAAACGGAACACACACAAGAACAGCCTGAAAGGCAGCGCGAGAAAGCCACACGATAAAAAAGAGGAGAAAGACCAACGAACATAGCAGCGGAAAAGCAGGCCCCGAACCGTAAACCACCGAAGGGAGCAACGAGACAATAGGAACAAAAAACCAGCAAGCAGGAAATAGCCAAAACCAGCCGAAGCAGGAACAGTCCCAAAACGC ACACGAAAGCACAACGCTGCCACCGGGAACACCACCAGGCCAGGCTAAAGGAAAAGAAACCGAA GGGCGGAAGTGAACAACGGGCACGCCACAAGAAAGACTAACCAAAGACAACAAAGAACGAAGGA ATACAAACAAAAGACGAAGGAACGAAAGATACAGGAGGAACAACAAACAGCAAGAAGTAAGAAACCAGAAGGACGGCAGAACCAGTGCGGGCCCACCACCAAACAACAAGGCATACAAAACGGGAACAAGCCACAACCGACTAGCGGCACAACAGCAAACAGCAAAGGATGGGCAAGGCACAAGCAACAGGCGGAGATAACGACCACAGAGGCAAGCAGCGACGGTAGGAAGGCACCAACAGCAAGAAGCCCGTGC AACAACGCAAGGGCAAGGCGAAAAATGACCGGGAAGAACCCGCGACACGGGAGTGGAGAACAGACGACCCGCCGCACAGACTAGAAGAAAAGAGACAGCAGAGACACCCTCACGCAAAGCAAAGACAGGAAACCAAATAGGGCCGAAACAACCCCCGCCACCCGGTAAAAGAAAGAGAGAACAACAAGGAAG AT AC GAG C AAAAAC AAGAAC C AAC C C C AAT AAGAC AG G C AAGAAAAC AGAAAG C GAG TGC GAAA GACAACACGACAAAGCGGAGATAAACAACGACAAGGCACGAGGAGGAAATAAGGGAGGAACGCG ACCGCAACAGAACTGAGACGAAAGACCAAACCAGAACGCCGTACACCGGGGCAGGACAAGCGAAACAAGTGCAAGACCGCGAAAACCAGCCCACAACTCGAGAAAGGAAAACCAGGACGAAGGCATAA CACCGGAGGCGAAGAGGCAAAACGGTCAAGAAAAACAAAAAGGGAAAGAAGCCTAGCGAAGCAA GGGAAGAAAGCAAAAAGTCCACACACGCGGGGAAAAAGGACCGACTCGAAGGCAACAAGGGAAA CGCGAACGATGACCGAAAAAAGAAACCCGCAGGACAATACGCCAGCCAACCGGAACGGAAGAAA CTAACGACAACGAGAGGACACGAGAACCGTACAGGGCAGGCGCAAACCAAACCGCCATAAGCAC CAGACGACGAAGGGGCAAAAGTGCGGAAACGAAACCAAAAGAGGCGAAATACAACCCAAAAACC GACCAACCACACATCCAAGGAAGGGGGGAAAACGAAACGAGTAAGCAAAAAACCGGCAAGCACGCGGAATGAAACGAAGAACACAGAAGGCGGCAGCTGACGCCAAAGCGGCAACAAAACAAACATCA ACGGCAGGAACGAGAGGGAGAAACATAACAACCCAAAAAGGAGACGAACAAAATCGCACCCAAA CAGCGCCGAGGACAACATGAAAAGGCGAGCAAGCGGCACACGGGATACAAAAGAACCCAAAACG CGCCAAAAATCAACCAAAGAGAACGACGACGGCGCAGTCCAAAGCCCACACGACAACCACGAGA ATAAGAACAGACAAAAAGCCACCGAAGCATCAACACAAAGACAGCACAAGGAGGCGGTCACCCG GCGAGAAAACAAAGGGAAAGATACACGCCCAAGGCAGAAAACCAAAAGCTAGCAGCGAAGCACG AAAACAAAACGAATCGCGCCCCAAAGACGAAAGCGAGAGACTAAGAAGAACGGAACAGCAGGAA CAACGTAACAAGGAAGAGAAGGACAAACACGACTAACGGAGAAAAAGCAGGACCCAGAGAGTAAACGCCACAAACACAGAGGGCGACAGTAACAGCGCAAGACACGCAACAAACGACTGAACAAGCCC GCACCCAAAGGGGACCGTAGAGCAACCGGGCAAGAAGAAACAAAATAACGAAAAAACAAACAAA GCGGAAAAATAGAAAAAAAGCAAAGGGGGAGAAGGCGTGAAACCGAAAGAAGGAAGCACACCGC ATAGCACAGGACAAAGGACAAAAAACCAATGGAGGAGAAAACGGAACCACCAAAGAGTACACAA ACCACACACCCCGGGCGGCAGTGAAAGGAACACAAAAAGACCCGACACCTCCACGCGCGGAAAG CCAGACAACCAAATCAGCAAACAACAGCAGGAGAAGGAAAATAGAAAAAGAACCAAGAAAACAA AGCCATCGAAACGGGAAGCCCAGAAGAACAAACTGAAGAAGAAAAGCAGACACAAAAAAGGTAA CAAAAGAAAAGGCCAACAGCAGGAGTCCCAACGACCCAACACCCCCGCGGACATAGCAGCGAAGGCAAGAAAGGGACAAAATAGGAACGAACGACACACAAGGAGAACGTCAAAAAAGGGCGAGGCAA GAGCAACAATCCAAGGAACCGAGCGGAGAAAACGCAATAGACAAAGCACGAAACACAACAGCAA ATCACCCAGAAACGACCAAAGACAAGGGATGAGGAACACAAAAAAAGCCCCAAAGACTGCGAAA GGACAAGGGGAAGAACCAAAATAAAAGGGCAGAAACGCAAACCACCCCCTCCAAGAGAGGGAAC ACACACCAGGGAATCCGGGGAAAACGACGAAAACAGACGGCTAACAGGAGAAAAAAAGCGGCAG CAGACTCCCAGACGAACAAAGACAAGACAAGAATGGAAAGGGAAAAGAAGAAGGAGCGCAATGA AC AAG C GAAC C AAGAC AGAAAC AAAT AC C C C G G C AAAC AAAAC AGAAC C C AG C T AAGAGAAGAAAGACAGCAGCGGCCGAGTACAAAGGGGAACAACCAGAACCAACAATGGCCCAAAGCAAGCACCC AGGGACCCCTAAAAGAAACCCCACGACAGGGCAAAAGTAACCAAAGGCAGGACAGGAAACACCC GTAGACGAGAAACCACAGGGGCAAAAAACTAAGCACAGCACGAACGAAGGAGGAAGGTGAGCCA ACCACACGCGAGGGCCGCCCGTCACAACAAGAAAAAAGCAAACCCGGCCTAAACAAAGGAGGAA CAACAGGCCAGCCTCAAAGAAACAAGGCCGACGCAAAACGATGAAAGGGCGGCGAGGCAGAGAGAGAAATCAGGAACGCAGGCAGAGAGCGGGGGGCTAACGGAAAAAAAGCCAAGAACCGAGGCTAC AAGGAAACAGCGAAGGAGCGAGCGCTAGACGAAGGAAGCGACAACCGCAACCGTCCCCAGCCAA AC GAAC AC AC G GAAAAC T GAC G AAC C GAG C C AC C AC AC C AAC AAG T C G C GAG C C AAAAC AC AAG AACCAGAAATAACCGGAAACACACGACCGGGAAGAAATCAGAAGGAGGGACAAGGAGGACGGAA ATACACGCGGGGGGAAAACCACGAGGCGATAACAGACCAAGCACGAACACCAAACCATCCAGAA GCAGAGGAGGCCGGACGCCCATACCGCAACGAGCCAGAGAAAAGACCAATGAGAACAGAAAACA AAGACACGAAAAGTCGACAGGAAGAAGCGGCAAAACAGACCTCAGAAAAGAGACAAAGCAAACC CCAACTGAGGGGGACGGGGGGAGGCCGGCACAGTAAGAACGCCAGACAAAGAACAAAAAAATCC GACCAACAACACCCAACAACGGAAATAACGCACAACACCCCAGAAACAGAACATGCCGGCGAGG CCAAAAACACCACGCGATAACCAAACAGGAAAGGAAGAACCAAACTCACACGCCACAGCAAGAG AAAAGGAAATAAAAGCGACGAGCCACGGGCCAGACACTAAGCAACGACAAAAGCAAGCAAGACC GTGAAGGGACAGGAAGGAGAAACACAAGGTAACGCCAAAGAAAGAAAAACGAAAGAGTAAGGAA AGACAGAAAGGACCCAACAGATACACAGGAAACGGGACCAAAGACAGGGTAAAAAGCAACACGA CACAAGACCCACATGCCCCGGGGCCAAGAGCAAACAGGGAATGCCCGAACAGCCGACCGGAAAA GAACCTGAACACGCCACGAACACAGGGAGAAGCTCAAAAAACAAGGAGAAGCCAGGAAAGGTGG CGGAAAAACACAGCGAAACGGCGAATCCACCACAACACCCGCCCAGCGACAAATGGCCGAAAGC GAGACAGAGACGCGAGATAGGGCCACAACCAAGCGCCAACAGGCATACGAAAGCGCGAAAAAAA GAGCGAAGCTCGAAGAAAAAGCCACAGCAAACGAAGGTGGCAACGAGCCAGCCAACAAACGAAA ATGCCAAAAGACAAACCAACAACAACCGCTCGGCAGCGCAAACAGCCAAAGCAGAGCTGAGCCC GCCGGCGAAAACACCGGGACCTGAAACGGCAAAACGCGAAAAGAAGGCATCCGAAGCGAAACGA AAAAGGCACCCCGTAGCCGAACACGCGGAAGGACCAGAAGCTAGAAGAGCACGACCCAAAAACA CCACATTCGCAATGCCAAACCACCGGCCAGGAAGAAGCCCTCAGCACAGGCCCAACAAGACAGG C GAAT C GAGAC GAAGAAG C AAC GAAC G G G C AAT C GAGAGAAAC AAAAAGAAAAAAGAAC AT GAG ACGAAGCAACAGGAGCGAAAAAAGTGGCCAAAAGCAAAACCCCAACAAGCAATGAAGGAGAACG AGAGCAAAAGAAAGACTGGCCGCGGCGACACGAGACGCGACCAGTGCCAGAGAGGGAGCCGACA AGCGGACGTGCCCAAAAGACACACGCAAGAGAGAAATGGCCGAAAAAAGCAACAGCCAGACCGG TGCAAACCGGCAACGGGCGAAAGGACGATGCACACGGCCGACAGAAAACGGAGGACTACGGCAA GCGAAACACCGAGCAGCGACTCCGAAAACAAAGCGCGCAAGAGAACACTGGACAAAAGACCAGG AAAGCAAAGGAGTACAACAAGGGAGCCAAAAAAAGAAAACTAGGCAAAGGGGCAAGACCCAAAC CAACTGGGCAAAAAAGGGAAAAAGGAAAAGAATACGCGCAACCGGACGGAGCCAGACCCCTACC GCGGACGCACGGAGGCACAGAACGTGACACAACAAACAAGCACGGCAAAGAGTAAAGGCAAAAA AAGAACGAGACACGGCTGCCGGAGGGGGAGCCACCGCAAAAACCTACAAGCACCAAAACACCGA AAGAGAAATAACCCCGAAACGGGAACAGCAGAGGAATGAGGAGACGGCGGGGAAGAAAAAACAG T C AAAAAC AAAAGAAC C AC AAAG C C AC G TAG AAAAC GAAAAGAC AC AAAG C AC AG G T GAGAGAA GAACCAGCGCACGAAAGCCCTAGCGAAAAAGAGCAGGGCAGCCGAGCGTAAGCCGGACGGAAAAAAGCACACGAGATCAAAGACAGCCCGAAGCCACCGAAGCATACCAGCGCCAAGCACAAACAAAA GAAGTAAGAAACAAAAAAAGCGAAGAAAAAGATACAAAGGGGAAAGAAACAGAAAAAACATACA ACAAACAACCAGGGCCGCGGCCCATAAAACAGCGCAAACCAAGCAGAAGGGATAGCCGCGACAG AAACCAAAGAGAACAATAGAAGAAAAACAAACAACAAAGAAAAATACAAACAAAGAGGAAAGCC AAC G C G GAT C C AAAGAAC AAG C C AAAGAC AC GAAGAT C C GAAAAAC C C C C AAC AC AAG GAGAAA TAGACAGGCGAAACCACCAACAGCACCATACCGGCCAGAAAACCGAAGGGCAAAGGTCGCGAAA ACGAACAAAGGGACAACAGCTAGACGAGCAAAACGGAAACAAAAAACCTAAGCAAACAACCAAC AAGACAGCAAAATAGAAGAAACCGGGCGACAGCGAAGGGATACAAGGACACAGCAGAGACAGGG CAACTCAACGAACGCCGAAAAAGAGGGCAGAATAACGAAGAGAAAGGGGCCGAAAACAACTAAC C AC C GAAC GAAAG C GAC AC C AG AAT AAC C AC GAC AAC AAC AAAGAAAAGAGAT AGAAAG G G GAA GAGAGAAACAAACGGCTCGCAAGGAGGCCGGACGCAGCAGCGGCTAGCAAAGCCAAAGCAAGAC AGCGCAGATGAAGGACAAACAGGGCAAGCAAACAAATAGCAGAAGGAAAAGACAAGCCCAAAAA TGACACAGACCGCAACAAGCGACAACAGTACAGCGGACCGAACAAGCGCCAGAACATCGAACAG AGAGAAGGGCACGAAACAAATACCGAAACCGGAGGGAACAGAGAAGAATAAACAACAGCGCAAA GAAAC GAG GAAC T GAC C C GAGAC AGAGAC GAAG C AAAGAC T C GAGAAC AC AAGAG C C C AAAAG G ACCGTGACGAGAGGACAGGAACAAAGCGGGACTCACCAGAGAAGCAAGAGAAAACGAGACTGCA AAAGGGCACGAAGGAACGGACAAGTCAAAGAAACGCAAACAACCCGAAAAAATAGACAAAACAA ACGAAGAAACACAGAATCGACAAGGAGAAAAGCAGCGGAAACAATAAAAGAGACAAGGCAAACA AGCCGGCATAGAGGGCACCACGAGAGCAACGAGGACTGGCAAAACCGGGCCCAAGAGAAAAAGA TACGACAAAGGCAAAGGAAGAAAACCGATGCCAGGAAACGCCCAAACCAGGAGAAGTACCAACA AG GAAAAAAAC GAC AG C C AAT AAC AGAC AAAC AAC GAGAGAAAAAC G C T AGAAAGAC AC C AGAA AGCGGAGAGCAATGCACAAAGAAAACAAGCACGGAAACACTGGGACAAAAGACCGAAGAAGCAG G GAC T AC C C C AC AAAAC C GAGAAAC G C C AAGAT AAAAC AAG C AC AC GAC C AAC AC C GAC AT C C A AGCAGAAAAAAGCACCGCGCCCGATACAAAAAACGACACGCAAAAAACAGGATAGCACAAGGGG CAGACCACAGGAACCGTGGCGAAGCGGCAGCGAGAAGGCGGCACTAAAAAGCAACAGCAGGACA AGGACGCATAGAAGCGGAAGCGGAGGAAAGAGAAAGTCGAAGCCCCGGCAACCAACGAGGCAGA TACGACAAAGCAAGCCACGAACGAACCGTCCGGACAAGCAGGAAAGCGACGAGCAGTAGGACGA AAAACGCAAAGCAAAGCGACTCCAAAGCAAGAAAACGAGAACCAGGGCTGAAACCAACAGAGAC AAC AAAC AG C AG T C AC C AGAAC AAGAC AAAC AGAAAC AC C T AGAAAAC C G GAAC C GAG C AC C GA GGACTAAAAGACGAGGGCAGACCAAGAAAACATCGAGAAAACACAAAAAGAAAACGAGCCTGCG AAAC AGAAAC AG C C GAGAAAC GAC T AAAC G GAAC GAC C AG GAC GAAAAG GAG T AAAGAAAAAGA ACCACCGGAGAGCAACTACCACAGGAAGAAGGACGAAAGACGGATCACGGAAGGACAGAGGGGA GAACCGGATGGAACAGAGAAAGAAGAGAACAAAAAATAGGCGAAAGGGAGAGCACGAACGAGCA TAAGAGAGCGACGCAACGAGCCGACAAATGCGCACGGCGGCGCAAGAAGAAAACGGTGGGAAAA CAGAGACAAAAACACAACCCTCGAAAACAGCCCGACACAGCACAAAAGTAAAGGGAAAGCGAGG-n-AAAGGGAACACCTCGAGAAAACGGCGGAAAAGAAAACACCTAAAGACGACAAACAACCACGAAG GAACTAAAGAGGCAAGAGGAACGACCAAAAAGTAAGACAAAAAGGCGGGCAACAAAGGCGTCAA CGCAGACACAAAAACAGCGGAGCCTGCAGAGAGGACGGCGAAGAACAAAGACTCCACAAGGGGC CCAGCGAGCACACAAGTCCACGAAAGAAGAAAAAGAGAAAGCCATCACACAACAGGACACGGAA AGAAAACCTAGACCGAGAAACAGCGGAAACAGCAGGTGAACCCAGAGGACACGAGGCAAAGAAG TAACGGGAACGCAACGAAGCAGCACAGCTGAAAGAAAGAAGGAGAAACCAGGGGACTAACGCAC CGCCAGAGCAGAAAGAAGAATGCACGAAAACACAGAACCAACCAGCACTCACCGGGGACCGAAG GACCGAAACGCATACAGAAGGAAAGCAACCAGGCGCGGCATGAACACAAAACGGGACAGCACAG CGAGTAGGCCGCAAAACCGCAGAGCCCACAGATGGGAAAGCACGAAGCAACAGACCAACATAAA ACAGAAAGGCGAAACACAGAAGCATCGAACAGCCACAGCAAACCAAAGGACATGCCCGCAGGGA GCAAGGCCGCGAGGAGTAAAAGAGCAGAAAAACAGGCGAAGGAGTAGGAGCAAACCAGCCAAGA GAAAG GAG T G C AAG GAAAAGAG C AAC AC AAGAAGAAT AC C AAAAG C GAAC AAC AAC GAC AC GAG TGCAGCAAAAGAAGGGCCAAGACACAACTACAAGGACAAGAACAAGAGCGCAAGGGTCAGAAAA CCCAACGACAACAGGCGAAGTACAGAACGAAACGACAGCCCACACCAGTCAAGGGAGAACCAAC AACCAGAAAACCTGGCGCAAACCAGCACCGAGAAGAAACATGGACAGAACGACGAGGGGAAACC AAGCTAAACGACACGCACGGCACGGACGCAAATGGACCAAACAAGAGGACAAAGGCAGGATAAC CGGCAAAACCGAGACGGAAAAAAATGAACGAAACAGGCAAAGGGACGCCGGATGACCCAAACCA CCACAAGAAAACAAAGTCAGAAAACGCGAAAACGGGAAGAACGGTCACAGAAAGGAAAGAACGC AAAGAAAATGAAACCAACGACACCGAGCGCAGAGCGTAAGCACGAAGGCAACACCAACCCAACG TACCAAGAGAAACCGAAACGCACAAACCTCAGGAAAGCCCCCGACCACAGACGGCCTAAGAGAA CAAGAGGCGAAACGAAGAGGTAACAGAAGCAGAACCCCGAACGGAAGCTGGAGAAGAAAAACAG CAGACAACCGAATGCCAAACAGCAACACGACGACAGGAAATAAAAAGCCACACCCGGGAAAACA GAACTGGCGAGACAGCACGGCGAAAAGGCCAGTACGAAAAGGACAAGCAAGGAACAAGCGTGGG GAACAGAGCAGAGAAACAAGCGAATGAAACACCACGAACGAAGCGCAAAAAGTAACGGAAGAAA GACAACAGCGAAAGCATAAAAACGGACAAGAGAGAGGCAACAAGTCCAACGGAGAAGAGAACGC ACGAGAAGTGACAAAAGGCAAGCGAAAAAGAAAGGGTGCAGAGACACAAAAGGACACCAGCGAA TCACCCAAGGAAAGAGGACGGAACCGGATAGGCGGCCGACAACCAAACAAGAGAAGTGGCAAACGACAACAAGAAAACGCGAAATGCGGAACCGAAGGGCCCAGGACGAAGGTACAAAAGAAAGACAA CACAACAACAGATCGCAAGGGCAGGCAGGGACGACAGCGCTCGCACCCCCGAGGAGACAAGACC GACGTGAAAACCACGCCAGGGACACAAGCCCATCACCAACACGCCCAAAAAAGGCCAACCTACA ACCCACCCAAGAAGGCACCAAAAGTGGACGAAGGCAAAAACACACCCCGGAATACAAAGGACAG CCGAAAGAAGGGGACATGCCAAAACCAAAAGACGGAAAGAAGGGTCGGAAACGCGACAGGCAAA AGAAAGCCTACGGAACCGAAAACAACACGGAGGAAATCGCACAACAAAACAGACGCCACAAGGC TACACGCGGAAGAAAGACCGCGAAAACATGCGAAAACAAAGACCGCACGGAAAAAATCGGAAAG AACGAAAGACAACGCGAAGCTCCAAACGGAAACAAAAGACCAGGGAAATCGAACAAAGAAGGAGACAGGGACACACTAGGAAAAAAGCCAGGAACAAGCCAAAGTCGAAAACAAACACGAACCGCAAA GGGGTGCGGAACAACAAAGACGCCCGCGGAAATAAAGGAACGGCACCAGCACGACACGGATAAA ACCACGACAAAAAACAAGCCGAAATGACGCGGAAGGCGCCACAGAAACGCAATGGAGCAACGCA GCAGGCCCCGAAGAAGTCGGCCAGAAACGCGCACCACCGACAAATACGCGAACCAAAGACCAAG AGAAG C AAT C AAAC C AGAG GAAAC C AGAC GAG C AAAT GAAC GAAC AAG C AGAAAGAC AAAC AG C TAAACCACAAGACAGCGCCAGAGCAGAATACCAGAACCCAGCCGGGCCCGAAAAACTCCACACC AGCCAAACAGCAACGGGCAGTAACGAAAACACCGAAACAACCAAACAATGAAAGAGCAGGAGGG AAACGCGGGAAATAGCAACCCGCCAACGCCGAAAGAAAAGTGCAGGGAAACCCAGGCCCGGGAA GAGGTAAACCAAGAAAAGCCAAAAAGGAACGCTAGAAGAGCGCAGAAGCCAGGGCGACAATTCA CTATGCCACAAAAGAACCGGAAAACAACGCCTCAGCACACACAACAGGAACAACGCCAATGAAC GAAAGGGAACGAAACAAAGCGGATAAAACAACAAAGGCGCCGAACGAAAACTAAAAAGGACCCA GGCGCGAGCAAGGCGTGGCAAAAGGCGCAAAAACAAAAAAGGGTCGCCCAAAAAAGAACAACAG ACGCAAATCCAAGACCACCGAGAGCAGAACGACCGTGGAACGAGAGCCGCAAGCGAGGACCAAT AACACAACCCAAGCAACCCAAGCGGCGTAACAGGCGCACAAGAAACACACGAGCATAAAAAACG AC C GAAAAG C GAAAC C C AC T AAAC AC AC AAGAAAC AAAAC C AAAAC G T AG C AC C AGAAAC C C AG AGGAAACCAGATAAGAAAAAGAGCCAACGCGGAGAAGCGTACCAAACCCAAAGAAGGACCAAAA AAGTAAAAACCACGGCAAACAGCAGGACGACTAGCGCAGGACCCCACAAACCAAAAGAGTAGGG CCCAAAAACGAGGACGCGGCACGTCAAACCAAAAGAACGACAACAAACAAATGGACAGAAAACG AGCGAAGCACGCGGGTAACAACAACCCAAAGAAGCGAAGGAAATACACAACAAACAACCAACAG AGGACCATAAAAGAGCAAAGAAACGAAGCCGAAAATACGACAAGGGGAAAGAAGCCGAACAGAT GAAGGGGAAGCGACCGGGCGACAAACATAAAACAAGACCAAAACCCCAGCGCAGATAGAGCGAG C AAAAC AGAAC C GAGAAC AT AC AC AGAAC C AAAAG C GAGAAC AG GAG T AAAAGAGAAC AC AGAG C AAC C AAC GAAT AC C AAG GAC AAC GAGAAC AAG GAAAAC T AC C GAC AGAAAC AAGAAAC AAAC C GCGTGCCACGAGGAGGAAACGAAAAACGGCATACCAACCCCAAGACACAAACGAGGACGTCGGA ACCAGGCGCCACCACAAGAAGGCTACACGAGACACACGGGCACGAAGAGGATACACAAAAAACC AAGAAAAAGAGGCCATGGACCAAAACAAAGAGGCGACACACAATGACCGCCACACGCAAACCAA ACAACCATCACAAGCGCCGCCAGGGAAGAAACAACTACAACGAAACACACACAGGGAAAGAGAT AAAGGACCAAAAGAAAAGCAACAGGAATCAAACACACCGAGCGGAGAAAGGGAAGTGCAACAGA CAAGAACCGCCAGGCAACCTGCCGCCGCCAGCCAAGGAAACCAACAATAAACACAGCAGGACCA AAAGACAGACGTCAAGAGGCCAAAAGCCCAAAAGGGCAATGGACCAAAAAAACAAAAACCCCAA ACGTACAACAACCGGAAAAAGAACAACAACGTGGCACAACACGGGCCGAAAAACCAAACTGAGG GAGGACACCACGAAACCCAGAAATAAGAAAAAAGCCCGAAACGCAGAAAACTAGCAAGCGCAAA GAAGGAACAAAGAAGTGGACACAAAACAAAGCCCAAAAAACGATCGAAGGCAACAAAAGAACAA AACCGAATGCAAAAGGCGAAGAAAGCGAAACAGAATGGAAAGCGCAAGAAACCAAGCAAAAAATCAACAGCACCACACAGACGAGACAAAATCCAAACCGGCGACAACGGAGAGCAACATCGGAGCCAAGAAAGGACAAAACCAGAATGCACAAACCACACAAAGCCAAAAGAGCTGGCGAGCCGAAACAAA AAGCAGCCGGGTGAACCACAAGAGAAGAAAAAAACAAAATAACGCACAACGGAGACGCCAAAGC AAC TGC GAAC AC AAGAC AAC AAC AGAC GAG C T AAAAAC C G C AGAC AGAGAG C GAAC GAG T AG G G AAAGAAAGGGCACCCAACAACAGTGCCGAAAAAAGAAAGGACAGCAACACCTGGGCACCGGAGC AAAAGAC G GAGAC GAT AC GAAAAC AAAAC C C G C C GAGAG GAC G T AAC AC C GAAAGAGAC GAAC A CCGCAACTCAGCCCCCACCGCCGAAAGAAAGAGGATAACGAAAACGCGACCCGCCAAGCCCCGT GGGGGAGAGCGGCCAAACCGGGCACACTACCAAAACGGACAAAAAACAAGAAACGTAAAAGGGA AAGCCAGCGAGCCCACCAATGACCAAAAAAAGAACAGACAGCACAAATCAACGAGAAACCGCGC CCAAGCCAGAGTGCCAAAGGAAAAACCACGGCCGGCAACTCAAAAGGGCAGCCCACGCAAAAGA AAATGAAGAAAACCCCCCAAAACGGGGACCATGCACGCGAGAAAAAGCCGCAGAACCCATAAAA GAAAGACAAGAAGCAAAAAAGACTACGAGGAAGCCCCGGACAACAAAGGGGTAAAAAGAAGAAG AAGAAAGCCCACGGATAAAGCAAACAAAGGGGCCAAGAACGACTGGAACCGAGAGCGAGGGAAG AAAAAACTGCCACGCGGAGCAGAGGCAGAAACCAATAAAGAAAGGGCCAGAAAAGAAAGAAAGT GAAC AG C AAGAC AAG C AC AGAG C AC CAT CAGAGAC AAAAC C AC G C AAAC AAAAAG T GAC AC C C A CAACACAAGCCCGGAAGCGTAAGAGAAAAGGGAAGCAAACCACACGATAGGACAGAAAGAAACG GAGACACAAACTCAGAACAACGGGAGACGAGCCCGGCAATAGGAGAAGAGGAGGCGGGGGAAAA AAATAGACAAAGGAAGAGGGACGGAGGCAAATCAACCAAGCCCAAACAGAGCCGCAGGATGACA AGGGGCGCGCACCGACGGAGCAATAAAAGAGGACGACAAAAGGAGCAAAGATACACAGAAAAGC AAGCCAAGAGAAGAATGGACACACCACAACCGCCCGGCAGGAATGAGAAAGACAAACAACCAAG AAGGGGATAACAGCACGGCGACCCGACCACCCAGCTAAAAGAAAAAACAAGACCACACACAAGT GACAGAGGAACAAACAACCGGCCCAGCTAGACCCACACCACGAACAGGACACAGGTCGCAAAAA AACCCACAAGAGACAGCAGTGCGAAGCAGCACGCGGGAGGGGCCGCCTAGAAAAGGCAACACAA CGGCAACAACGTGGACGAACCACGGACGCCACCGAGCCCTAGACCCAAAAAAGCAAGACAGACA CAATAAAAAAACCAGAAAAAAGAAGCGCCAATACAAACACCCAGAGAAAACAGGAAGCATAGCA AGACCAACACCGGGAAAAAAACATGGAGAAAACAGGCGCAGAGAGGAGAAGTCCAAAACGGAAC GGAACCAGCGAGGAATAGGCACAAACGCCCGAAACAAGGACCATCCCAAGACCAAAGAAAGGAG CGCCAAATAAAGAGAGCGCACAAAAACAAGGGAAATACCCAGGCGAAAGGAGCACACCGCCAAT GGCGAACAAAGAAACCAACAAACAGAGTGCACCAGGGGCAGAAAAAAGGGCCACCTAAAAAGCA GCACAAGACAACGAGCAGCTGACAGAAAAGGCAGGAACGGAAAGGGATCCGGGGGCAACGCAAA C AAAC GAG C G C T C AGAAAAAAAC AC C AAGAGAAAGAC C C T GAAG C C AAAGAAAAGAC AAGAAC C CCATCCACGCGCACGGGACGAGCAGCAGGCGTCGAAAAAACGGGGCCAAGGGCAAGCGATGCCG AAAAAGCAACAGAAAGGAGAACATCCAGCAAGCAAGGGCAAGCAGGCGGGATGACCGAAAAAAG C AGAC AAAGAC AC CAT C AC GAAGAAC GAAAGAAAC GAG C AAAAT AGAGAAC G G C AC C AAC AC G G AACCCCATCCAAAACGGAACCGCACCGGGGCCACGTCCCCCCAACAGCGGCAAAGGAGAAAAATAGACGAGCGCAGCACCGACCAGCCGGATAAGAGAAAGAAAGGCGAACGGGGCCACTGACGAAAGCGCCGGGCGACAACCACCATACAAACCAGAGAGCAGAAAGAGAAGGATGCGAACCAGGACAGCG AGCGACAAAAGTCAAGAGACGGCAAAAAAGAACACACAGTAGGACACAAAGACCGGCCAAACAC AAGTAGCGAAAAAGCGAGACAGGGACACCAGTCAGGACCCGGGACAGAGGCACGCGACGTCGAC GAGAGGGCAACGCAGGACAACCCTAACCGACGCGCGAAGCCAAAGACGCCATAGAAGAGCAAAG AAC C C GAG GAAGAAAT C C C GAG AAAAAAC AGAC AGAC GAGAAAT AG C G C AAC AG G GAG AC AC C C AAGGGGATAGGCAGAGGCGGCGGCGAGAAACGCGCTAGCAAAAGAGGCACACAGAAAGAAGAAT AAACAACGGGGAAAGCACAAACAGGAATAGAACGAAAACAAAGAAGCAAACAAGATCGCCACCC CACAACAGCGGGCGGAACATAGCAAAGCCAAAGGAAACCCGGCAAGCTACCCACGACAACAGCA CGAGCGAAAGCTACCGCCGAAAGAGAAAGGCAACACAAGTCAAAGAACACGAACAGACCCAGCA GAATGAACAACAAAGACCGCACAAGCAGCAGTACCGCAAACAAGCCAAACAAGACACAATAGAA AACACCACAAGGCAAGAAACAAATAAAAACACGAAAGCCACACGCAAAAACTACAGGGAACCAC GCAAACCCAAACGAGTACAGCCAGCAAGCACGCAAGAAAAAGATCAGACAACAACCAAAACAGA GAAAGGCTAGGGACCAAACAACCACGAGGCAAAACTAGGGCGGAACGGAGAACGGAGACAAAGT AAGAGGCGGGAGAAAACGCAAAGCAACTACCCCAAGAACACACCAGGGAAACGACTCGAACGAA ACGACGCGAAAGAAAGCAGTGCCCAAACACCCCAGACACGGGGCCCATAAAACCAACGGACACA CGAGAGGAGGATCAAAGCAGGAAACCAAGGAGAGGCAACTGAACGAAAGCAAGCAAACAAAAAC GCGTACCCGGAAAAGAGAAAGGAACCAACAGTGAAACGAGAAGGGCAGGACCCAACGGATGAAC GAACAACGAAAGAACGCAAACCGTAGAGGGCACAGGCGAGAGCCACGAGGATCGACACAAGCAA CAAAGCAACACGCACTAGACACGCAGACAAAAGGGACAAAACGTACAACAAAGGAGGAAAAAGC C AAAC C G T AGAC C AGAGAGAAAC C C C AAC C C C GAC T C AC C GAC AC AAAC C AAAGAC C C AAAG C T AAGCGGAGCGCAAAGAAACGCGAGACATGACCGAAACAAAAGCAAAAGGACAAAGTAAGACAAA GCACACAAGCAAACAAAAGTAACGAAACCAAGACACAACACCACCAATAGCCAGAGGAGGCCCC GGAAGGCAGACTCCAGCCCAAACGGACCGAACCCCACGATACAAGCGAGACGACCAAAAGAACC ACCTCGAAGCGCCGAAGGAGCACCAAACGGCTAGAGCGACCCCAAACACCAACAGGAGATCCCG ACGAGACACAAAAGAGGGCAAAATAAGGAAGAAGCCCGAACAGGAGGCAGCTAACGAAGCGCAA CCAACGCACAAGAAGTGGGAGAAGCCCCACGCAAAGACAAAGCTGCAGGCAAAGAAAGGCGAAA CGCGGACTAGGACCCAAAACAACGAGAGGGAGGAGTAACAGGAAGGGCCACGAACAAGCGGCCT GAAACGCCCAAAAGCAAACGAAAGCAATCAGGGAACAGAAGAAAAAACGCGGAAATGCCCACAA CCACAAACACACGAACCAATCAAGACAAAACGGAGGCAGGAGAAGAATGCACCCGAGGCACAAC CCCCACGCCCGTAAAAAACAAGACAGCGAGCAAAAGCACTAGAGAACCAAAAAGACCCCCGAGC ACCTGGAGCCAACAAAACAACGAGCACGGCATACGGAAAAACAAAACGGAGAGGGCAAGTAAAG ACAAAAGAGCGAGGAGAAAACCATAGAAGAGCCGAAAAGAAACAGCACGCATTCTTACTGCCAC ACACGAAACGAAAAAAGCGACCTCAGCCACACCAGGGAACGGGCGAAAGATACCCGACAAAGGC ACGAAAGAGACAAATGAGGGGACAGAAAGGCGGCAGCAAGGGTCAAGGGCAACGGGCCAGAAAG CGAAGGTCGCGCGACAAGAAGCGCACGGGAAACGTGCCACCACCAAAGGGAAAAAAGAGCAATAAAGAAACCAAGAGAAGCGGGCGCCAATAGAAAAGCCAAGACGAGACACGCCAACTACAACGAGA AGAAAACAGGCAGGAAAATCAAGCCACGAGAACGCAGAAAAAACCATGAGGAAAGGAAAAGAAA AAACGGGGAATAAAAGAACCAGAAAGGAGACACAGGGATCCAAAACCCGGGAGGACAAGCACCA AAT AAC AC GAG C AC AAAG GAAAC AGAAAC AT AG C AC C C AAAAGAC G C AAG C AC AGAAG T AGAC A ACAAGCCCAAACACCGACCCCATAAACAGGCCAGCCACCACCAAACAAAATAAGAAGGAAACAA AACAGCAAAGCGCATACGCCACAGACCCAAACGGAGGAAAGATGGAAACAAAAACAGAGGACAG C G GAAAT C AC AAAAC C AC C AGAC C C G G C C GAGAC T C C AAC GAAG C AC C GAAAC AC GAGAAC AT A CAAGAGAGAACAACCGAAGAAAGGGGTAAACGGAGGCAGAGAAAAAGAGCCAAGTACCCAGAAA C GAAC C AC C GAG C G C C CAT AAG C AAAC AAAC GAC C C AAAC AC C C CAT AAAAAC AAAG C AAGAAA GGAAGCAAAGTACCAGAACGGCAACGCGAGGCGACAAGTGCACGCGCGAACCAGAACGCCAACC CGTAGAGCGAGGCACGAAGAAGAAGGGGGATCAGAACACGACCAGAGAAGAACAGCAATACAGA CCAGCGGGCAAGGACCAAAACGTCGAGAAGGCAGGCGGCCGAACAGACCCTGCGCAACACCACA ACGGCAACGAGAAATCGGGAAAGAAAGAAGAGACGCCGAGACTAACCGCGAGCAACAGACGAAA CAGAGGTAACAAAGGCCCGCGAGGACAAGAAGCCTCGACACGGGACAAACCAAAGGCCAGAGTC GCCAAAACCCACGACCAGGAAACGACTAAGCCACGACAGGGACACCAACAAAGATCCAAAAACC GAAACAAAACAAGGAGCCTCACAAAGGAAAAACACAACCGAGAAAATAGAAAGACAACACAAGG GGGGGAGCGATAACGAAACCGCCCCAGGCAACGACCGATGAAAGAAAAACAGCAAAAGCGGAAA AGTGACCGAGGGCCCGAGAACAAGCCCAACTGAACGACCAAAGCAACGAGGAAGGGCCTACACA CGAGCCGACGAAACACGCCAACTGAAAACGCAGGAGCGACCACCGAGCAATAACAAACCGAACC AGAGAGGCGGAACATCCAGCAGAAAAGACACGGACACGAAGATCAGCAAAAAAAGGAAGAGGGG AGCGAATCCGACAGGGGACAACAGCCCGGCGCCATAGAAACAGGAAACCGCCAAGAAGCACATA AACCAAGACCCCACACCCCGCAAAGATAGAGCGGGGAAACAGCGACAAACAACATGGCGAAAAC AAGAAACAACGACAAAAATACGAAACGAAAGGAGAACAAGAAAAAATGAAGGGAAAAAGGCCAA CCCGCGCCAATCCGCCGGAACAGCAGCCAGCACCGAAGTAACAGGACACGAGAACAAAGGCGAA G G T AAAC GAC AAC GAC C AC AC GAGAAAAC AT AAC AGAAAC GAC C C GAAC AC GAG GAG G T AAAAG AAGAGAGCAAAAAACCAGAGCCTGAGCCACACCACGAGACGGCGGACCGATGGCACGAGAAAAG CAAAACGAAAGCCATAAAACAAAAGAAAACGCCCCAACGGACTAGAGCAGAAAACAGCCAGGCA GAGAACTGGAAGAAAAACACGGAGGAGCCACGCATAACCAAGAGGGCAAAAAACGGCAGAGGTA GAGAGCGGGGACCGGAGAAAAAGAAGTGAGAAAGCAGGGAAAACCAAACAGAGATAAAAAGGGA C C GAAAC AAC G C GAC C AG T AAAAG C AAAAAGAAGAAAC AG C GAC AG TAG AC GAC AG GAGAAAAA C AAAAC C GAG T C AGAAAAAAGAGAC AGAGAG C C C GAC C T AAAAC GAAC C GAAAAAC C C AAG C AG AATAGAGAGCGGAGCCAGCAAAAACAAGAATGACGGCAAGACAACAGCCACGACAAGCTCCACA ACGCCGACACAGCCACAACGCATCGGGAACGACAAGCCAAACACAAGAACTGGACACGGGACCG ACAAGAGAAGAGACTACCGCAAACCCCAACGGCAGCAAGCCGTGCGACCGAAGAGACGCAACAC GGGCAGTGCGACGGGGCGGAACAACACGGCAAGATAAACGGGCACAGACGGAACGAAAACGCTAAACGCCAACACGCAGCCCAAAGGACATCGAGCAGAGAACACAGAAAAAAAGGCATAAAAACGCC ACCAACAGCCAGAAGGCCTAGAAAAGCACAGACAGAAGCGGACAGCTAGGAGAACCCAGGCACG AAAACCAGGGTCGAGAGGAAAGGGGGGCGAAGAGAGGGTAAAGGAGAACCAGGACCAACCCAAA AATCCCAGCCGACAACGAGCAACAGAGAGCTACCCGAACGCCGGCAAACGACCAAAAGTACCAA GCACACACAACAAAAACACAGATCCAAGAAGAACAAAACAGCCGGAAGAATCGAAAAAGCCGCC CGCAGCCCACGAGGTACAACACGACAAACCAAGCAAGCGAACTAGACAGGGAACACAAAAACAA AGAGAGTCACCGCGAAAACAACGCAACAAAGGGATGGGACGAAACCCGGACAGAGACGAGCCTA AAAACAACGGGGGCGAACACGAACAATGCCCCACGAGAACAGCACACAAGGCAATGCAGGAAGC ACAAAAAAGAACCCCCAATACAAAAAACAACAGCAGCGGCGGACCGTAAAAGAGAACCCGGCAA AAGCGCAGGCTAGCGAAAGAACCCGAACGAGAGGGCAATCGAACAAGAACCAAAAAGCGACGGG AGTAGCCAAGCAGACGAGAGGAAAAGCAGCTAAGCCACCGAGAACACGGCACAGGGAGTAAAGA GACAGCCGCCGACCCCAAAACCTGAAGAACAACAAAAGCAGAGAGAAGCGTAGCGCCAAAGGGC CAGCCCGCCAACCCTAGGAAAACCGAAAAAAGGAGAACGCGGTCAAAACGAAGAGACAGCCCAC AC AAAG T C AGAG G GAAAAAAC AAC AGAGAAGAGAT AC C AAC G C GAC GAAAAGAC GAC G GAAG T G ACCAGAAGGCAAACAGGCGAGCCGGATAACCCAGCCGACCAAGACAACAAGCGATGGAAAGCCG C AAGAAGAAAAGAC C C AC T AAAGAAC GAGAAC AAC GAGAG C AG CCCTCCGC C AAC AAC AC GAG G ACACAAAGACTCAAAGCGGGGGCCAAGCAGAAGCACCATGAGACACGAGCAGGAGAAAAGCCAA AATCGAGAGAGGCCACAGGGAAGAAAAGGATAGGGCACACAGAAAGCAAGAACAAAACTGAAGG GACGACAAGGCAGAACCAAACGTACCCAACCGCAGAAAAAAACGCCGCCGTAAGCAGAGAAGGC GCACGACAAAGGCATAACAAGGAACGGCAGAGCCGGACAGAATCGCGACACGGAAACGAGCGCG AAGGGATCAACACGGCGCCAGACAAACGGGAAAGTAACGAAAAGGAAAGAACAGCAACACCATG CCCAAGCCCACGCCCGCGCAGACAAGTCAAAAAGAGAGGAGCAGAGCACCGAAATAAAGGCCAC CCCCACCCACAAAGGGCATACAAACCGAACAAACAAAAAGAGGCCATGCGAGAAACAAAACGAG AGAAAGAGAATCAAAGGAACAGAAAGGCCAGCAAAAGATCGGAAACACCCACAGAGACGCGAAA AATCGCCACAAACCAGGGAAGAAACAGCCGTACCAGACAAAGCAAACACAAAAAACCATGAAAC GAAAGGCCAACCCGAAAACACATAAAAAGAGACAGAACGAGGGGGAAGAATGGCCAGCAGGGAC GAAAG GAAC GAAAC T AGAAAC G GAG C GAC GAG C AC AC G C C AAT AGAAAAGAC C AAAC C AC AAAG CGCCAATAGGCCGGGAACCAAAAAACAAGGGGCATACAACAAGAACCAGAAGCCAAGACAAATCGGGAACAGAAAAAGCGAGCAAGAAAATCGGAAAGAACCAACCAACGGAGGGCACTGGCAAACAA ACAGAAAAGAAACACCACTCACGAGGCACAACGGCCAACAAAAACATAAGAAGGAGAACAGAAG CAACCAAAGATGAAGCGCACAACACCGCAGACCGACGATAGACAGAAAGAGCCAAGCCCGAAGG AGTGAAAAAGGACAAAGGCGCGGCGCGGAATAACAAGCCACACCAGGACAGAGCAGAATAGGCG AAGAGAAAACAACAACAGACGATGCACCCAAGACACAAACCCAGAACGACTACGGGGCCACAAA GCAAGCAAAAAGCGTAGCGCGCACCGACAACAGAGCAAGAGATGGGCGACGAGGACAGAAAAGA GAAGCGTGCGACGCCGAAGAAGAGACAGACAAGATAACCCGAACCAAAAGCCCCAAAAAGCCTCGGGCCGCGAAGGCCGACAACGAGAAGTCAGACCAAGAGGGGACAGAAAGAAAGCTGACCCGGCG AAACCCACGAGAGAACACTACGCAGACAACAGACGAAGGGAGCCAGTAGACGAACAGGGGGCAG GAACAAAAGCTAAACAAGCAGACGCGAAAGACAAGAACTAAAAGGAACCCAGCCGGAAAAGGGA AG T C AAGAAAAAGAAAAAC AGAAAAAAGAAT GAG C C C AGAC AAAGAC C GAG C C G G GAG T AGAAG AACCAACGAGAGCACCAACACCTACAGAAAGAAACGCACGAAACACGGGCTGCGAAACGGACGA CAAACAAAAAAGGATAGACCAGCCCCGCGCAACCAGAGCGGATACGGCCCAAAAGGAGAAACCG CGAGGGTAAGCAACGAAGCGCACGAGAAGGACACTGAAGCCCCCCCGAAAACCAACCACCACTG ACCACGAAAAAAAGCAAAGCCGACCCTAGAAAACAACGCAGACGACAGCGGAGATGGGACCACG CCAAGAACACACAGACAATCGAAAAAAACAAGGCAAGAGGAGAAGATGACAAAAACAGAAAAGA GGCACGCAACTAAGAACAGACAAAAGAACGACGACAACTGAGAAAACCGCCAGCGAAGGAACAG GCTCCACCCGCACGAGGAAACCAGCGAAAATAGGCGAAACACAAGAGACGACGGAGGATAGAGC CAAGACGCGCGAGAGCAGGAAGTAAACAACAAGCGAAAAAAAGCAAACAATAGGGGCGAAAACG AACAAGAGGGCCAGTGGAGCACCGGAGGAGGACCACAGCAAATGACGCAGCAAAACACCGAGGC GAAAC AT AC C C C G GAAGAGAAAG C AC AAC G C GAG T AAAAAC C C AAC C AC C AAC C AGAC GAAG TA ACAACCCGACACCACAACGAGGAACGTAAAAAAAGCCAGGCGGGGCAGAAAAAATCGACAAAAA CAAAAAAACCCCACAAGCTCCCCCGCAAGCAAAAAAGCCACGCGCATAAGAACAAACCCAAACC ACACGAGGGGTAAAGAGGAAAAAACAAACCCGAGAACGTACCGCAACAGCCAACACACCCAACG AATAAACGGACCAAAAAGAGGAACACACGATGGGAGGCCAAACAGAACGACAGGCCGATCGCAA GACGAACACGGCAGAAGCCCAATAAGCAGCAAAAAAACAAACGGCCAGAATAAACGAGGGGAAC GAG G C AGAGAAC C C T AGAAGAG C C AAGAAG C GAC AAAAC G C AT T C

[0163] SEQ 6ACTGGTCTCCTGCCGGGAGCAGAAAGAACGAAAGAACCTCAGCCAACCGAAACAGGCCGCGAGC CCTGAAAAAGCAGGGCAAAGGAGAGCCCGCTACAACCAAAACGGAAAAAAGAGGCAAGTACCCG AGCAGAGGAGCAAAAACGCAACTAAGGAGGAAGGGACCGAAACAACGAGGTAACGCAAGAAGCA GAAGCGAGGGCACATAAAACCCCACAAGACAAGCCCGGAAAGTACAAAAAGCGAAAAAAAGGAA GCCCAATAAAAGACAACGGGAGACGCAACAAAGATCACAGAGCCAGACAACGAAAAGAAAAATA GCGCCGGAACAAAAAAAGGCGAGAACTGAACCCAAGAACCACAGAAGCACAGGATGAAAACACA GGACCACGGCAACGCAGCTGAAAAAAACAAAAACGCGAGAAAACAATAGAAAACCCAAAACAGA CCCGGGCAGATAGAAAAGAACAACACGAAAAACCCAGCTAGAAACAACAAGGGAGGGCACAAAA AG T AAAAC C C AAGAGAGAAG GAAGAAAAAG T G C AAG C C C C C C GAC C G C C C AC AAAAAAT C AGAA ACAACAAACAGGGCACCAGGAATGAGCAAGCGGAAGAAAAGGACCAAAAATAGAGGGAAGGGAA AGCCCGAAGGCAGGACAAAAGAAAACGACGACCAACCCAACAAAGAAAAGCAAACAAAAGACGC AAAGCGGAAACCACCGACAACCGAACAAGAACAGGCACAGACGAACCGGCGCGCACAGCAAAAA CCAGGACCCGAAAGAACGCCACGGAAACCAGAACCCGAAGGGCGCAGCCGGCCCCAAAAGAGAG CCGAAAGACGAACAAACGAGAAAGGAAACACAAAGGCACCAAAAAAGCACCACCGAAGAAAGCGCAACCGAAGAAAAGACCCCCGCAGACGAAACCGAAGCCGAACAGGGGCAACGGAGGAAAAAGCAAACGACAGGCGCGCACCGACGGGGGCAACAAGCCAGCGCAGCAGCACAAAGAGAGAGAAAAACGGGACGAGACAAGACAGAAAGAGCACACAAAAAAGACAAGCCGCCAAGGGCGCCAAACAAGACAGGAGGGACAACGGACAAAAAACCAAAGGCCAGGGGAGCAAAAGAAAGAGGCAGGCAAGCAAACACGCACCGGCACCAAAAAGGAGCGAAACGCAAAAACGAAGCGAAACGGGCAAGAACAGAGACAATAGAAGGCGACAAAAAGCACAAGAAGAGTACGGGAGAGGCCGCGCCAAACAACACCTACAAACCAAGAACGAGCAACAACGAAATGAGGGGCAGCACAAACGCAGGGGGCGCTAGAACAAGAGGACCGGGCCGCAAACACTCCCAGACAAAGAAGGAGCGACGCAGAGTAAAAACGGAACACACACAAGAACAGCCTGAAAGGCAGCGCGAGAAAGCCACACGATAAAAAAGAGGAGAAAGACCAACGAACATAGCAGCGGAAAAGCAGGCCCCGAACCGTAAACCACCGAAGGGAGCAACGAGACAATAGGAACAAAAAACCAGCAAGCAGGAAATAGCCAAAACCAGCCGAAGCAGGAACAGTCCCAAAACGCACACGAAAGCACAACGCTGCCACCGGGAACACCACCAGGCCAGGCTAAAGGAAAAGAAACCGAAGGGCGGAAGTGAACAACGGGCACGCCACAAGAAAGACTAACCAAAGACAACAAAGAACGAAGGAATACAAACAAAAGACGAAGGAACGAAAGATACAGGAGGAACAACAAACAGCAAGAAGTAAGAAACCAGAAGGACGGCAGAACCAGTGAAGGACCAAAAACAGGGCACAGAAGCGGAAGGAAAAGGCAGCACGCACCAAAACGCAACAACCCAGACGAGAAGGGCCAAGCACAAACGAAACGACCGAAGGCGAGGAAGAAGGGAAACGAGAAAAGAACCAAGGGAAAAAGGAGAAACAGAAGCCGCCAAGCCAGGAGAAAGGGCGGACCACGACCCGGGGAGGAACAGAAGAAAACAAACAAAAAACACGCACGCACCAAGAACACCCAGAGAAAAAGAACAAAGCCACGCGGGAAACCGCAACAGACAAGGACAAACGACCACACAAGGCAGACAGCGACAACCAAAAAGAGAAAGGAAGAAACAAGGAAGCAAAGGGCGGACGAAGAACGCACACGAACAAACCGACAGCACAAAAACCGCGCAGGCGACCGCAACCCGCAAAAGACCGGAGAGACGCACGGCCAGCAGGCAACAGCGGCAGGAGAACAAACAAAACGGACAAAAGGCAGCGCCGGAAAGAAAGGACAAAAAAGCAGACGCCCAAACGCAAAACCAAAGCAAACCACACAAAAAACACGCACGGAAGGGAAAAAGGAACCCAAAAAGAAAACTCGAGAAAGGAAAACCAGGACGAAGGCATAACACCGGAGGCGAAGAGGCAAAACGGTCAAGAAAAACAAAAAGGGAAAGAAGCCTAGCGAAGCAAGGGAAGAAAGCAAAAAGTCCACACACGCGGGGAAAAAGGACCGACTCGAAGGCAACAAGGGAAACGCGAACGATGACCGAAAAAAGAAACCCGCAGGACAATACGCCAGCCAACCGGAACGGAAGAAACTAACGACAACGAGAGGACACGAGAACCGTACAGGGCAGGCGCAAACCAAACCGCCATAAGCACCAGACGACGAAGGGGCAAAAGTGCGGAAACGAAACCAAAAGAGGCGAAATACAACCCAAAAACCGACCAACCACACATCCAAGGAAGGGGGGAAAACGAAACGAGTAAGCAAAAAACCGGCAAGCACGCGGAATGAAACGAAGAACACAGAAGGCGGCAGCTGACGCCAAAGCGGCAACAAAACAAACATCAACGGCAGGAACGAGAGGGAGAAACATAACAACCCAAAAAGGAGACGAACAAAATCGCACCCAAACAGCGCCGAGGACAACATGAAAAGGCGAGCAAGCGGCACACGGGATACGAAGCCGGACCAGAGAAGGCAAGAAGC GAG C AGAAAC AAAAGAAC G C C G AAAC AGAC AAAC AAGAAAC AGAC AAC AAAAAC AC AAG G C GAG GAGAAAAGCGCAAAGAAGCAAAACCGCGCCAGCAAAAAAGCAAGGAACCCCCGGAGGAGGGGCGCACGAGCGAGAACAGCACAGAGGAGCGAGCGAAGAAACCAAGAAAAAGCAGAACAACCAGGACG AAAACAACACGAAACGCAGAGGCAAAAGCCCAAGACGACAGCGAGAGCAGCAGAAGCAGAAAAA GAGGCAAGACCAAACAAAGGGGGGAGAGCCGAGGGGAAGAGAACGAAAGACGCAAGGAAGGAAA GAAAG C C C AAAAC AC AAC AC C G C C AAC G C AC GAC GAAAC C AAAAC AGAC AG GAAAAC GAC G GAA CAGAGCAAGAGCCCCCCGGCGGAGAGAAAACAGAAGAACAAAAGCCAGAGAGCAAAAGAGGAAG AAAGCAACAAGCAAAGGGAACAACACAGAAACGACACGGCAGGAAGAAAAACCAAAAACAGAAA AAAAGGCACAAGGAGGACGGAGAACGACGAAAAGACGCGCAGCGGATACACAAACCACACACCC CGGGCGGCAGTGAAAGGAACACAAAAAGACCCGACACCTCCACGCGCGGAAAGCCAGACAACCA AATCAGCAAACAACAGCAGGAGAAGGAAAATAGAAAAAGAACCAAGAAAACAAAGCCATCGAAA CGGGAAGCCCAGAAGAACAAACTGAAGAAGAAAAGCAGACACAAAAAAGGTAACAAAAGAAAAG GCCAACAGCAGGAGTCCCAACGACCCAACACCCCCGCGGACATAGCAGCGAAGGCAAGAAAGGG ACAAAATAGGAACGAACGACACACAAGGAGAACGTCAAAAAAGGGCGAGGCAAGAGCAACAATC CAAGGAACCGAGCGGAGAAAACGCAATAGACAAAGCACGAAACACAACAGCAAATCACCCAGAA ACGACCAAAGACAAGGGATGAGGAACACAAAAAAAGCCCCAAAGACTGCGAAAGGACAAGGGGA AGAACCAAAATAAAAGGGCAGAAACGCAAACCACCCCCTCCAAGAGAGGGAACACACACCAGGG AATCCGGGGAAAACGACGAAAACAGACGGCTAACAGGAGAAAAAAAGCGGCAGCAGACTCCCCG CGGAAAAAACAGGCGGCCAAACGAGCGCGAGAAAGCAACCGAGCACGACGGCCAAGCAAAGAGC CAAAAAAGCAACCAAAGAAACGAAGGCGGCAAAAAAAGACAAGAACGCAAGGAACAACCAAAAC AAACACCAAAGGCAAGAAAACAAAGAGAGCGAACAGACGGAGACGGACCACCCGACGAAAAGGA AC AAG GAC AC AAAGAG C AG G C AAGAAC AAC AC C AC GAC AGAC GAAAAAAC C C C AC AGAAAAAGA GCGAAAGCAAACCCAAGACACGGGGGAGGACGCCAGAGAAACGGACGGACCGAAAACCAGCGGA CCGCAGACAAGGAAACAGACAGAAAAGACGCGACCAAGACACGAGAGGGGAACAAACACCGACC GAAAACAAGGAAGAGAGCAGACAGAAGGAAAAGGAAAAGGAAACGAGAAAACCCAAACCAACGG GCCGCAACCAAGGGAGCCGGGAACAGGACAACCCAAAGACAGAACACAAGAGCAGACCGAAAAA AGGCAACGAACAAAGGCAAACGAACAACGGGGACGGAAAGCGAAAAAAGCGCCGGCCCAAAAAC C AG C AC T GAC GAAC C GAG C C AC C AC AC C AAC AAG T C G C GAG C C AAAAC AC AAGAAC C AGAAAT A ACCGGAAACACACGACCGGGAAGAAATCAGAAGGAGGGACAAGGAGGACGGAAATACACGCGGG GGGAAAACCACGAGGCGATAACAGACCAAGCACGAACACCAAACCATCCAGAAGCAGAGGAGGC C G GAC G C C C AT AC C G C AAC GAG C C AGAGAAAAGAC C AAT GAGAAC AGAAAAC AAAGAC AC GAAA AGTCGACAGGAAGAAGCGGCAAAACAGACCTCAGAAAAGAGACAAAGCAAACCCCAACTGAGGG GGACGGGGGGAGGCCGGCACAGTAAGAACGCCAGACAAAGAACAAAAAAATCCGACCAACAACA CCCAACAACGGAAATAACGCACAACACCCCAGAAACAGAACATGCCGGCGAGGCCAAAAACACC ACGCGATAACCAAACAGGAAAGGAAGAACCAAACTCACACGCCACAGCAAGAGAAAAGGAAATA AAAGCGACGAGCCACGGGCCAGACACTAAGCAACGACAAAAGCAAGCAAGACCGTGAAGGGACA GGAAGGAGAAACACAAGGTAAAAGACGACGCGAGGAACCACAAAGAGCACAACAAAAGGGCAACAAACAGAGCAAACGCACCCAGAGCGAACCGCACACGGCGAAACGGAACACAACGCCGAGAACAG AAGCGAGCAACACAGAAAACAAACAGCGGAAGGAGCAAACCGCAGAACCCGGGCGACCAAGAAG AGAAAAAGGCGAGCCGAAGAAACAGGAAAGCCGACCAAAGGCGACGAAACAAGAGCCAGAAAGA AACACACAAACAAAACCCACCACAACGGACACAAAACAGGACCAAGGCAGAAACCACAAGGACG CAAGGACGAAACCCCGCAACAAGAGACGCCGGGAGAAAAGAAAGAAAGGAAAAAGAACGACAAA CACCGAGGGGCCAGGAAAAACAAAGACAGAAAACAACGGCCACCCAAAGAACAACACACAGGCG CCGCGAAACACAACAACGACGAAGAAAAGCGAAAAAGCACAGGCAAGCGCAGGAACGCACCCAG ACAACAAAACACCAAACGAGGAAAACAGAGCCACGGACAAGCGAACAAACGCACCAAAAGACAA CGCCCAAGGAAAAAGCACCAGGCGGAAAAATAGAAGAGCCGAAAGGGCGAAACAAGAATTCGCA AAGAGACCTGCGGCCGCAGGCTAGGTGGAGGCTCAGTGATGATAAGTCTGCGATGGTGGATGCA TGTGTCATGGTCATAGCTGTTTCCTGTGTGAAATTGTTATCCGCTCAGAGGGCACAATCCTATT CCGCGCTATCCGACAATCTCCAAGACATTAGGTGGAGTTCAGTTCGGCGAGCGGAAATGGCTTA CGAACGGGGCGGAGATTTCCTGGAAGATGCCAGGAAGATACTTAACAGGGAAGTGAGAGGGCCG CGGCAAAGCCGTTTTTCCATAGGCTCCGCCCCCCTGACAAGCATCACGAAATCTGACGCTCAAA TCAGTGGTGGCGAAACCCGACAGGACTATAAAGATACCAGGCGTTTCCCCCTGGCGGCTCCCTC GTGCGCTCTCCTGTTCCTGCCTTTCGGTTTACCGGTGTCATTCCGCTGTTATGGCCGCGTTTGT CTCATTCCACGCCTGACACTCAGTTCCGGGTAGGCAGTTCGCTCCAAGCTGGACTGTATGCACG AACCCCCCGTTCAGTCCGACCGCTGCGCCTTATCCGGTAACTATCGTCTTGAGTCCAACCCGGA AAGACATGCAAAAGCACCACTGGCAGCAGCCACTGGTAATTGATTTAGAGGAGTTAGTCTTGAA GTCATGCGCCGGTTAAGGCTAAACTGAAAGGACAAGTTTTGGTGACTGCGCTCCTCCAAGCCAG TTACCTCGGTTCAAAGAGTTGGTAGCTCAGAGAACCTTCGAAAAACCGCCCTGCAAGGCGGTTT TTTCGTTTT C AGAG C AAGAGAT T AC G C G C AGAC C AAAAC GAT C T C AAGAAGAT CATCTTATTAA GTCTGACGCTCTATTCAACAAAGCCGCCGTCCATGGGTAGGGGGCTTCAAATCGTCCCCCCATA CGATATAAGTTGTTACTAGTGCTTGGATTCTCACCAATAAAAAACGCCCGGCGGCAACCGAGCG TTCTGAACAAATCCAGATGGAGTTCTGAGGTCATTACTGGATCTATCAACAGGAGTCCAAGCGA GCTCGATATCAAATTACGCCCCGCCCTGCCACTCATCGCAGTACTGTTGTAATTCATTAAGCAT TCTGCCGACATGGAAGCCATCACAAACGGCATGATGAACCTGAATCGCCAGCGGCATCAGCACC TTGTCGCCTTGCGTATAATATTTGCCCATGGTGAAAACGGGGGCGAAGAAGTTGTCCATATTGG CCACGTTTAAATCAAAACTGGTGAAACTCACCCAGGGATTGGCTGAGACGAAAAACATATTCTC AATAAACCCTTTAGGGAAATAGGCCAGGTTTTCACCGTAACACGCCACATCTTGCGAATATATG TGTAGAAACTGCCGGAAATCGTCGTGGTATTCACTCCAGAGCGATGAAAACGTTTCAGTTTGCT CATGGAAAACGGTGTAACAAGGGTGAACACTATCCCATATCACCAGCTCACCGTCTTTCATTGC CATACGAAATTCCGGATGAGCATTCATCAGGCGGGCAAGAATGTGAATAAAGGCCGGATAAAAC TTGTGCTTATTTTTCTTTACGGTCTTTAAAAAGGCCGTAATATCCAGCTGAACGGTCTGGTTAT AGGTACATTGAGCAACTGACTGAAATGCCTCAAAATGTTCTTTACGATGCCATTGGGATATATCAACGGTGGTATATCCAGTGATTTTTTTCTCCATTTTAGCTTCCTTAGCTCCTGAAAATCTCGAT AACTCAAAAAATACGCCCGGTAGTGATCTTATTTCATTATGGTGAAAGTTGGAACCTCTTACGT G C C GAT C AAC G T C T C AT T GAT AC C T GAAAC AAAAC C C AT C G T AC G G C C AAG GAAG T C T C C AAT A ACTGTGATCCACCACAAGCGCCAGGGTTTTCCCAGTCACGACGTTGTAAAACGACGGCCAGTCA TGCATAATCCGCACGCATCTGGAATAAGGAAGTGCCATTCCGCCTGACCT

[0164] SEQ 7ACTGGTCTCAGCAATGCCAAACCACCGGCCAGGAAGAAGCCCTCAGCACAGGCCCAACAAGACA GGCGAATCGAGACGAAGAAGCAACGAACGGGCAATCGAGAGAAACAAAAAGAAAAAAGAACATG AGACGAAGCAACAGGAGCGAAAAAAGTGGCCAAAAGCAAAACCCCAACAAGCAATGAAGGAGAA CGAGAGCAAAAGAAAGACTGGCCGCGGCGACACGAGACGCGACCAGTGCCAGAGAGGGAGCCGA CAAGCGGACGTGCCCAAAAGACACACGCAAGAGAGAAATGGCCGAAAAAAGCAACAGCCAGACC GGTGCAAACCGGCAACGGGCGAAAGGACGATGCACACGGCCGACAGAAAACGGAGGACTACGGC AAGCGAAACACCGAGCAGCGACTCCGAAAACAAAGCGCGCAAGAGAACACTGGACAAAAGACCA GGAAAGCAAAGGAGTACAACAAGGGAGCCAAAAAAAGAAAACTAGGCAAAGGGGCAAGACCCAA ACCAACTGGGCAAAAAAGGGAAAAAGGAAAAGAATACGCGCAACCGGACGGAGCCAGACCCCTA CCGCGGACGCACGGAGGCACAGAACGTGACACAACAAACAAGCACGGCAAAGAGTAAAAGCGAA ACGCGCAAGGGCAACGCAACCGCAAGGGGGAGGCCGGAAAACAGAAGAACACGGGAGCAAAGAG GCCGCAAAACGGCAAGGGGAGGACCGGAGCCGAAAAGCCCGGAACACCCGAAGAAAGCGGACGA C GAAAC GAGAAC C C AAGAAAAAG G C AC GAAC C C C C AAG C GAAAAAC AC G C C AC AAC AAC C AC AG AGACAGACCGCAGACCAACACAACAAAGACAGACGCGAAACCCCGAAGCCGAGAAGAAAAGCGC CACAACAAAGGGAGAAACAAAGGACACGCGAGACAAGCGAACAGAAACGACCCCAACAGCGCGA GAGACAAAAAAGGAACGGGCCAAAACACCCGAAAAGCCCAGAAAACACGGAAGCCGGCACGAGA AAACAGGGGAACCAACCAGAACAACCGAAAAAAGCGGAACAGACAGAGAAACAACAAAGAAAAA AGCAGAGAAAGCAAAGACAGCAACGACCGCGAGACGCAAAAACGAGCCAAGAGGAACCACACGG ACAACGGGCGAAAAAACCACGACACGAGAGAGGACGGAGCGGGAAGCAACGCAAAAAGCAAAGA CATAGACAGGCGAAACCACCAACAGCACCATACCGGCCAGAAAACCGAAGGGCAAAGGTCGCGA AAACGAACAAAGGGACAACAGCTAGACGAGCAAAACGGAAACAAAAAACCTAAGCAAACAACCA ACAAGACAGCAAAATAGAAGAAACCGGGCGACAGCGAAGGGATACAAGGACACAGCAGAGACAG GGCAACTCAACGAACGCCGAAAAAGAGGGCAGAATAACGAAGAGAAAGGGGCCGAAAACAACTA AC C AC C GAAC GAAAG C GAC AC C AGAAT AAC C AC GAC AAC AAC AAAGAAAAGAGAT AGAAAG G G G AAGAGAGAAACAAACGGCTCGCAAGGAGGCCGGACGCAGCAGCGGCTAGCAAAGCCAAAGCAAG ACAGCGCAGATGAAGGACAAACAGGGCAAGCAAACAAATAGCAGAAGGAAAAGACAAGCCCAAA AATGACACAGACCGCAACAAGCGACAACAGTACAGCGGACCGAACAAGCGCCAGAACATCGAAC AGAGAGAAGGGCACGAAACAAATACCGAAACCGGAGGGAACAGAGAAGAATAAACAACAGCGCA AAGAAACGAGGAACTGAAAGGCGGGGGGAAAAAGCGCGCAGGAAAGACGCCCACAAACCAAAGAAACCAGGAAACCGCAAGAGGGGCAAAAGAGCAACGAAAAACAGAAGGACAAGAAGCAAGACAGG ACGACGACCAGACCAGCCAAAAAGAGCAGGAGAAGAGAAGCGGGGGCAAGAAGCAAACCACAGG AGCGCAGGCGCACAAGGCCACCACCCCCCCAGAAACCAAAGACGGCACAAAAAGAAGGGAAAAC CAAACCCAAAACGCAACAAGAGAAGGGGCGACAACGGAGCGAGAAACGAAAGGCCCAGAAAAAA GCCAAAGGCACAAGGAGAAGGCAGAAACCAAAAGAAAACGACAACAGAGGGAGAGGAGAACACA ACGCAAGCAAACCGAGAAAAAACAGACCAACAAACCAAAAAAAGAAAAAGGAACAGGCCAGCCC GAAAAAC AAAAAGAGAAAAGAC C C C GAGAC AAC AAC C AAGAAAC AC G GAGAC AAAAGAC AAAC G GAGGAAAGGAACAGCCGGGAGCAAACAAGAAAAACCACAAGAACAGGCGGACGAAACGGCCAAA AGACGGAAAAGCCAAAAGGAGGGGAGTACAAAAAACGACACGCAAAAAACAGGATAGCACAAGG GGCAGACCACAGGAACCGTGGCGAAGCGGCAGCGAGAAGGCGGCACTAAAAAGCAACAGCAGGA CAAGGACGCATAGAAGCGGAAGCGGAGGAAAGAGAAAGTCGAAGCCCCGGCAACCAACGAGGCA GATACGACAAAGCAAGCCACGAACGAACCGTCCGGACAAGCAGGAAAGCGACGAGCAGTAGGAC GAAAAACGCAAAGCAAAGCGACTCCAAAGCAAGAAAACGAGAACCAGGGCTGAAACCAACAGAG AC AAC AAAC AG C AG T C AC C AGAAC AAGAC AAAC AGAAAC AC C T AGAAAAC C G GAAC C GAG C AC C GAGGACTAAAAGACGAGGGCAGACCAAGAAAACATCGAGAAAACACAAAAAGAAAACGAGCCTG C GAAAC AGAAAC AG C C GAGAAAC GAC T AAAC G GAAC GAC C AG GAC GAAAAG GAG T AAAGAAAAA GAACCACCGGAGAGCAACTACCACAGGAAGAAGGACGAAAGACGGATCACGGAAGGACAGAGGG GAGAAC C G GAT G GAAC AGAGAAAGAAGAGAAC AAAAAAT AGAAAAAC C AAC C AC AC AC AC GAG G AAAAGAGAAAGGGAAAAGGCGAAAGCCCGAAAACGGCAAAGACCCAAGCCGAAAACGAGGAAAC CCAAAAGACGAAACAGGAACCAACCAAGAACAACGGGCAAACAAGAGACGAGAAAAAAGCAAGG AACAAAGAAAACCCACACCAGAAAAAGGCACAACAGAAGCGGGCCCCAGACAAAAACAGGACGA AAAAAAGCAGAAGGACACCGCAAAGCCAGACGAGGAAAGGGAAACCAAAAACGAAAAAAAGGGA GGCAGGACGGGCCGGAAGCAGAAAAGAACAACAAAGAAGGAACAGAGGAGAGCAACCAGAACAA AGGAACGGCGGAGAGGACAGCCCAACCACGACACCAGGCGCACGAACAAGAGCGCCGAAGCACG ACAGGGCACCAGAGGACGAACAGCAGAAGAAAAGACGGGCGAGAGAGCACGCGACAAAAACAGA AGAAAAAAAG C AAAGAC C AAAG AAAC AAAAAAGAAAC G C GAGAAAAAAGAC C AAC C GAG GAG GA CAACAAAGAAGGAGCAGGCAACAGCACAACAGCAAGAAAAGACGACAAACTCACCGGGGACCGA AGGACCGAAACGCATACAGAAGGAAAGCAACCAGGCGCGGCATGAACACAAAACGGGACAGCAC AGCGAGTAGGCCGCAAAACCGCAGAGCCCACAGATGGGAAAGCACGAAGCAACAGACCAACATA AAACAGAAAGGCGAAACACAGAAGCATCGAACAGCCACAGCAAACCAAAGGACATGCCCGCAGG GAGCAAGGCCGCGAGGAGTAAAAGAGCAGAAAAACAGGCGAAGGAGTAGGAGCAAACCAGCCAA GAGAAAGGAGTGCAAGGAAAAGAGCAACACAAGAAGAATACCAAAAGCGAACAACAACGACACGAGTGCAGCAAAAGAAGGGCCAAGACACAACTACAAGGACAAGAACAAGAGCGCAAGGGTCAGAA AACCCAACGACAACAGGCGAAGTACAGAACGAAACGACAGCCCACACCAGTCAAGGGAGAACCA ACAACCAGAAAACCTGGCGCAAACCAGCACCGAGAAGAAACATGGACAGAACGACGAGGGGAAACCAAGCTAAACGACACGCACGGCACGGACGCAAATGGACCAAACAAGAGGACAAAGGCAGGATAACCAAACGACAAGAAGAAGAAACCACCGAGGCCACGCGGACAAGAGAAAGAGCAAAAGAAAGACCACGACGGACGCAAAACAAGACGAGAGCCCCAACAAAACCAGGCACAAACAAAAAGAGCAAGAAAAAGAAAACCCCCGCAGGCAAGAAGAAAAAACAGGAACAGGAACGAGCAGGGCCCGGCCAACGAAGAAACAAACGCGACAACCCAAAGAGAACAAAGCGGCGGAGCCAAAAAACGCCAACACCACGGACAAACCAGGAAAAGCGAAAAAAACAAGCGCGAAAAAGAACAAACACAAAAAAGGAAACCCAGCAACACAAAGAAAACAACGCGAACAAGCCCAAAAGAAACACAAAGAACAGAAAAGCCAGGGAAAACGGACAAAAAGGAACACAACAGGGCAAAAGGACAAGCAACGGACCGGCACGCACCCCAAGAAGCCGGAACACGCAAAGAAGAAGGACCAAAACACCAGAGACAAGAGACGGGCGCAAGAGAGGACAACCAAAGGACCCACAACAAAAAGGCAACAAAACACCAAGAGAAAAAAAGAAAGCCACCAACACCAGCCCCGAGCAAGTGACAAAAGGCAAGCGAAAAAGAAAGGGTGCAGAGACACAAAAGGACACCAGCGAATCACCCAAGGAAAGAGGACGGAACCGGATAGGCGGCCGACAACCAAACAAGAGAAGTGGCAAACGACAACAAGAAAACGCGAAATGCGGAACCGAAGGGCCCAGGACGAAGGTACAAAAGAAAGACAACACAACAACAGATCGCAAGGGCAGGCAGGGACGACAGCGCTCGCACCCCCGAGGAGACAAGACCGACGTGAAAACCACGCCAGGGACACAAGCCCATCACCAACACGCCCAAAAAAGGCCAACCTACAACCCACCCAAGAAGGCACCAAAAGTGGACGAAGGCAAAAACACACCCCGGAATACAAAGGACAGCCGAAAGAAGGGGACATGCCAAAACCAAAAGACGGAAAGAAGGGTCGGAAACGCGACAGGCAAAAGAAAGCCTACGGAACCGAAAACAACACGGAGGAAATCGCACAACAAAACAGACGCCACAAGGCTACACGCGGAAGAAAGACCGCGAAAACATGCGAAAACAAAGACCGCACGGAAAAAATCGGAAAGAACGAAAGACAACGCGAAGCTCCACAGGCACACAGAAAAGCGGACCAGAAAACCCACAACGAAACCAAAGCCAAAAAAGGACCCCCCGGGGGCAACAAGGGGAGAACCACAAGACACACACGCGCAAACCAGCGGCCGGCAGAAGAAAGGGCAGAGACGCGCAGAACAACAAAACCGGCAACAGGCAGACCGAAGAAACGCGCAAACGAACGAACGAAAAAAGAAACAAGACCCGGCAGGGGCACCAGGCAAAGACGCGAAGCGGAAGGCCGCACCGACCCAGGCCCACGCGAAGGCAGGAAGAGAACGAAAGCCGACGCCAAACAAAAACAAAGGCGACAAGAGCGCCACAAGAGAAACGACAAAGACCGGAAGGAGAAGAAGCCGGCCGCGCCCGACCAAAAAACAAACGAAAAAAGAGCGCACAGACGGCACAAAAGCCGGAAACAGCGCGGAACCCAAAACAGAAAAGAAAAAACGCGACAAAAGAAAGACGCACAAAAACGACCCGCAGCAACACGGACCCGAAAAACCAGACGACAAAAGAAAACGAGAAAAAAGGAAGGCGGCCCACCAGAACCCCAGCGGCAAGGCCAAGAAACGCACAGTAGAAGAGCCAAAACGCCAAAAGCCAAATTCACTAAGAGACCTGCGGCCGCAGGCTAGGTGGAGGCTCAGTGATGATAAGTCTGCGATGGTGGATGCATGTGTCATGGTCATAGCTGTTTCCTGTGTGAAATTGTTATCCGCTCAGAGGGCACAATCCTATTCCGCGCTATCCGACAATCTCCAAGACATTAGGTGGAGTTCAGTTCGGCGAGCGGAAATGGCTTACGAACGGGGCGGAGATTTCCTGGAAGATGCCAGGAAGATACTTAACAGGGAAGTGAGAGGGCCGCGGCAAAGCCGTTTTTCCATAGGCTCCGCCCCCCTGACAAGCATCACGAAATCTGACGCTCAAATCAGTGGTGGCGAAACCCGACAGGACTATAAAGATACCAGGCGTTTCCCCCTGGCGGCTCCCTCGTGCGCTCTCCTGTTCCTGCCTTTCGGTTTACCGGTGTCATTCCGCTGTTATGGCCGCGT TTGTCTCATTCCACGCCTGACACTCAGTTCCGGGTAGGCAGTTCGCTCCAAGCTGGACTGTATG CACGAACCCCCCGTTCAGTCCGACCGCTGCGCCTTATCCGGTAACTATCGTCTTGAGTCCAACC CGGAAAGACATGCAAAAGCACCACTGGCAGCAGCCACTGGTAATTGATTTAGAGGAGTTAGTCT TGAAGTCATGCGCCGGTTAAGGCTAAACTGAAAGGACAAGTTTTGGTGACTGCGCTCCTCCAAG CCAGTTACCTCGGTTCAAAGAGTTGGTAGCTCAGAGAACCTTCGAAAAACCGCCCTGCAAGGCGGT T T T T TCGT T T T c AGAGC AAG AGAT T AC G C G C AGAC C AAAAC GAT C T C AAGAAGAT C AT C T T A TTAAGTCTGACGCTCTATTCAACAAAGCCGCCGTCCATGGGTAGGGGGCTTCAAATCGTCCCCC CATACGATATAAGTTGTTACTAGTGCTTGGATTCTCACCAATAAAAAACGCCCGGCGGCAACCG AGCGTTCTGAACAAATCCAGATGGAGTTCTGAGGTCATTACTGGATCTATCAACAGGAGTCCAA GCGAGCTCGATATCAAATTACGCCCCGCCCTGCCACTCATCGCAGTACTGTTGTAATTCATTAA GCATTCTGCCGACATGGAAGCCATCACAAACGGCATGATGAACCTGAATCGCCAGCGGCATCAG CACCTTGTCGCCTTGCGTATAATATTTGCCCATGGTGAAAACGGGGGCGAAGAAGTTGTCCATA TTGGCCACGTTTAAATCAAAACTGGTGAAACTCACCCAGGGATTGGCTGAGACGAAAAACATAT TCTCAATAAACCCTTTAGGGAAATAGGCCAGGTTTTCACCGTAACACGCCACATCTTGCGAATA TATGTGTAGAAACTGCCGGAAATCGTCGTGGTATTCACTCCAGAGCGATGAAAACGTTTCAGTT TGCTCATGGAAAACGGTGTAACAAGGGTGAACACTATCCCATATCACCAGCTCACCGTCTTTCA TTGCCATACGAAATTCCGGATGAGCATTCATCAGGCGGGCAAGAATGTGAATAAAGGCCGGATA AAACTTGTGCTTATTTTTCTTTACGGTCTTTAAAAAGGCCGTAATATCCAGCTGAACGGTCTGG TTATAGGTACATTGAGCAACTGACTGAAATGCCTCAAAATGTTCTTTACGATGCCATTGGGATA TATCAACGGTGGTATATCCAGTGATTTTTTTCTCCATTTTAGCTTCCTTAGCTCCTGAAAATCT CGATAACTCAAAAAATACGCCCGGTAGTGATCTTATTTCATTATGGTGAAAGTTGGAACCTCTT ACGTGCCGATCAACGTCTCATTGATACCTGAAACAAAACCCATCGTACGGCCAAGGAAGTCTCC AATAACTGTGATCCACCACAAGCGCCAGGGTTTTCCCAGTCACGACGTTGTAAAACGACGGCCA GTCATGCATAATCCGCACGCATCTGGAATAAGGAAGTGCCATTCCGCCTGACCT

[0165] SEQ 8ACTGGTCTCAACTATGCCACAAAAGAACCGGAAAACAACGCCTCAGCACACACAACAGGAACAA CGCCAATGAACGAAAGGGAACGAAACAAAGCGGATAAAACAACAAAGGCGCCGAACGAAAACTA AAAAGGACCCAGGCGCGAGCAAGGCGTGGCAAAAGGCGCAAAAACAAAAAAGGGTCGCCCAAAA AAGAACAACAGACGCAAATCCAAGACCACCGAGAGCAGAACGACCGTGGAACGAGAGCCGCAAG CGAGGACCAATAACACAACCCAAGCAACCCAAGCGGCGTAACAGGCGCACAAGAAACACACGAG C AT AAAAAAC GAG C GAAAAG C C AAAC C GAG T AAAC AC AC AAGAAAC AAAAC C AAAAC G T AG C AC CAGAAACCCAGAGGAAACCAGATAAGAAAAAGAGCCAACGCGGAGAAGCGTACCAAACCCAAAG AAGGACCAAAAAAGTAAAAACCACGGCAAACAGCAGGACGACTAGCGCAGGACCCCACAAACCA AAAGAGTAGGGCCCAAAAACGAGGACGCGGCACGTCAAACCAAAAGAACGACAACAAACAAATGGACAGAAAACGAGCGAAGCACGCGGGTAACAACAACCCAAAGAAGCGAAGGAAATACAAAGCAAAGAAGGAAAGAACACAACAGAGACAGCGCAGCACGGAAAAAAGACCAAACCAGACAAGACCCAAACACCACGAAAACACAAAGGAGGCAGGAAGGACAAGACCAAGCCAGGAAAAGGGGGGAAGCCACGGAAGGAAGCCCGAACGGAAGCAAGCGAACGAAAAAAACCAGCAGGGGCAAACGAAAAGGGACGAGCCAGGAAAGGAAACCACGGGAGAACAAAACAAGACACCAGGCAAGGGCAAAAAGAGAAACCAAAACCGCCAACGGAACCGCCCGGACACCACGCAACCAACCGACACGCGAGACGAAGCGGCCGAGCGGCAAAAGCGAGCGAGAAGAGAGGGAAGAACGAAAACAGACGACACGCCGAACAAGGCCCCACGGCGAACAGCCAACGCGAGCAACAAGAGCAAAGAGAGGGGAGGACGAACGAACAAAAGCCAAAAGAAAGAAGGAGGCGCGACAGGGCCAACCGAGCCGGAGACGAGCAGGGAGAGCACGACACAGCCGGACACGAGGCGGGCAAACCAAGAAAAAGAAAAACCAAGAACGAAAAACAACCCCAGAAGGCAAAAGTGCAACAGACAAGAACCGCCAGGCAACCTGCCGCCGCCAGCCAAGGAAACCAACAATAAACACAGCAGGACCAAAAGACAGACGTCAAGAGGCCAAAAGCCCAAAAGGGCAATGGACCAAAAAAACAAAAACCCCAAACGTACAACAACCGGAAAAAGAACAACAACGTGGCACAACACGGGCCGAAAAACCAAACTGAGGGAGGACACCACGAAACCCAGAAATAAGAAAAAAGCCCGAAACGCAGAAAACTAGCAAGCGCAAAGAAGGAACAAAGAAGTGGACACAAAACAAAGCCCAAAAAACGATCGAAGGCAACAAAAGAACAAAACCGAATGCAAAAGGCGAAGAAAGCGAAACAGAATGGAAAGCGCAAGAAACCAAGCAAAAAATCAACAGCACCACACAGACGAGACAAAATCCAAACCGGCGACAACGGAGAGCAACATCGGAGCCAAGAAAGGACAAAACCAGAATGCACAAACCACACAAAGCCAAAAGAGCTGGCGAGCCGAAACAAAAAGCAGCCGGGTGAACCACAAGAGAAGAAAAAAACAAAATAACGCACAACGGAGACGCCAAAGCAACTCCAAAGACAGAAAAAGGCCGGGCAACAAAAAGCAACAAGAAAAAGCAAAGCCAAGGCAGAAGGAAGCACCCAAGCGAGAGGCGAGACGGGAAACAGCACGGCCCCAAACGCAGACAAACCAAAAAGAAGCCAAAACAAAAGAAAGCCAGGAAAGGACACCCACGAAAACCACAGGAACCAAACCCAAAGGAACGGAAACGAGAACACGGAGCGACCAGCAGGCGGGGAAGGCCGAACCCCGGAAGCGCGCAAGAAAACACAACCGCAGAAACAGCAGAAACCGCGACAGCGGAAGCCAGCGCAACCAAGCCAGGGAAAAAGCAAAACAAGGAAAAAAGCCGGCGAAACAAGCGGCAACAACGCGAAAAAGGGGAAGGAGAAGGAGACAAACGAAACAACACAAGACCACGAGAGCCAAGAAAAAAACAACAAGGCGGGGAACGAACCGGGGGGAAGGACAAGAACCAGCCCAACAAACCCACACGCACCCCAGAGAGAAAGCGCACAAGGCAAGACGACACAAACAACCACACAACCAAACGGAACGCACAGCAGAGAAAGGGACAAACAACGGCCGGAGAGAAAGATAAAGCAAACAAAGGGGCCAAGAACGACTGGAACCGAGAGCGAGGGAAGAAAAAACTGCCACGCGGAGCAGAGGCAGAAACCAATAAAGAAAGGGCCAGAAAAGAAAGAAAGTGAACAGCAAGACAAGCACAGAGCACCATCAGAGACAAAACCACGCAAACAAAAAGTGACACCCACAACACAAGCCCGGAAGCGTAAGAGAAAAGGGAAGCAAACCACACGATAGGACAGAAAGAAACGGAGACACAAACTCAGAACAACGGGAGACGAGCCCGGCAATAGGAGAAGAGGAGGCGGGGGAAAAAAATAGACAAAGGAAGAGGGACGGAGGCAAATCAACCAAGCCCAAACAGAGCCGCAGGATGACAAGGGGCGCGCACCGACGGAGCAATAAAAGAGGACGACAAAAGGAGCAAAGATACACAGAAAAGCAAGCCAAGAGAAGAATGGACACACCACAACCGCCCGGCAGGAATGAGAAAGAC AAACAACCAAGAAGGGGATAACAGCACGGCGACCCGACCACCCAGCTAAAAGAAAAAACAAGAC CACACACAAGTGACAGAGGAACAAACAACCGGCCCAGCTAGAGGAGGCGACCAGGAAAAGAACA C AGAAGAAAAAAC C AAC C GAAG C C AAC AAC AC C C AAAAC AG C G GAAC AAAGAAC AAC C AAC G C G GCCGGAACGAACACAAAAAGCGAGCCGAAAACAGACGAAACACGGAACACACGGACACCAACAG CACAGGAAACGCAGCGGGCGCCAAGACAGACGACCACAAACACAAAAGAGCGGCGAAGCCGGAG GAAAAAGGCACACAAACAAGAAGCGAAACGAAGAGACAGAAACAGAGCGGACGGCAGGCAAAAC GGGACGACCACAAAAGAGGGACCGAAGAAAAGCCAAACCACCCAGAACCCAGGCCCAAACACAC GGAACAGGGGAACACCACGCGCCGGAAGCACCAGCAGGCAACAGACAAAAGGCAGCGCAAAGGC AACGAGCACCAACCAGGGCGAGGCCAGAAAAGACGAAACAAGCGAGGCGGCACGCAAACCACGA GGCGCACAGCACAGGAACGAGACAAACCCACAGGCAAAACGCGCGAGGAACAAACAGGAGAACA AACCCCGAGCGGACCAAAAAAACGAGAACCAAAAAGAGGGCGACAACACCTGAAGCCAAAGAAA AGACAAGAACCCCATCCACGCGCACGGGACGAGCAGCAGGCGTCGAAAAAACGGGGCCAAGGGC AAGCGATGCCGAAAAAGCAACAGAAAGGAGAACATCCAGCAAGCAAGGGCAAGCAGGCGGGATG AC C GAAAAAAG C AGAC AAAGAC AC CAT C AC GAAGAAC GAAAGAAAC GAG C AAAAT AGAGAAC G G CACCAACACGGAACCCCATCCAAAACGGAACCGCACCGGGGCCACGTCCCCCCAACAGCGGCAA AGGAGAAAAATAGACGAGCGCAGCACCGACCAGCCGGATAAGAGAAAGAAAGGCGAACGGGGCC ACTGACGAAAGCGCCGGGCGACAACCACCATACAAACCAGAGAGCAGAAAGAGAAGGATGCGAA CCAGGACAGCGAGCGACAAAAGTCAAGAGACGGCAAAAAAGAACACACAGTAGGACACAAAGAC CGGCCAAACACAAGTAGCGAAAAAGCGAGACAGGGACACCAGTCAGGACCCGGGACAGAGGCAC GCGACGTCGACGAGAGGGCAACGCAGGACAACCCTAACCGACGCGCGAAGCCAAAGACGCCATA GGCGAGAAAAACCACAACAGAAGGAAGGAAGCCACACGGCGGGAGGCGGAACCGCAGCGGAGGA AAAGGGCACGAGAGCGCACCGGCACACCACCAGGAGCCCAAAGCCGCGGAACAAGGCAACAAAA GGCAGAGGGCAAAAAAGCCACAAAACAGCCAAAAAACGGCGCAACACGCCGACCAGCACACGAA AAG C AGAGAAG C C C AGAAAAGAGAAAAAAC C GAG C GAAAAAAC AC C AAAC C AAAAC AG C GAAC C AAGCGCCCCAACCGGAACAAAAAGGGCAAAGCGGAGCCGGCAGAACAAAGAAAGCAACAGAAGA ACGAAGAAAGCGCACGGGGAACGGAACGAGGAGCACGAAAAGAAAGAAGAGAAAAGGCGCAAGG GCAGAACAGACGCAAACAGGAAGGGAACCAAGAACCGACAAACGAGAGCCAAGCGGAAGAAAAA ACGCACGACAAAGGAAAAAGACCAGAAAACCCAAACAAGCCGGCCGCCCACACAAACCCAACAG ACACGACAGGAACGGCCAACAAAAGGGAGGAAGGAGCGAGCAAGAAAACAAACCAGCAAAACGA GCACGAAGCGTAAGAGGCGGGAGAAAACGCAAAGCAACTACCCCAAGAACACACCAGGGAAACG ACTCGAACGAAACGACGCGAAAGAAAGCAGTGCCCAAACACCCCAGACACGGGGCCCATAAAAC CAACGGACACACGAGAGGAGGATCAAAGCAGGAAACCAAGGAGAGGCAACTGAACGAAAGCAAG CAAACAAAAACGCGTACCCGGAAAAGAGAAAGGAACCAACAGTGAAACGAGAAGGGCAGGACCC AACGGATGAACGAACAACGAAAGAACGCAAACCGTAGAGGGCACAGGCGAGAGCCACGAGGATCGACACAAGCAACAAAGCAACACGCACTAGACACGCAGACAAAAGGGACAAAACGTACAACAAAG GAG GAAAAAG C C AAAC C G T AGAC C AGAGAGAAAC C C C AAC C C C GAG T GAG C GAG AC AAAC C AAA GACCCAAAGCTAAGCGGAGCGCAAAGAAACGCGAGACATGACCGAAACAAAAGCAAAAGGACAA AG T AAGAC AAAG C AC AC AAG C AAAC AAAAG T AAC GAAAC C AAGAC AC AAC AC C AC C AAT AG C C A GAGGAGGCCCCGGAAGGCAGACTCGCAGGAAAAGAGCGAAAAACAAGGGCACAAAGCCAGAAAC CCACCGGGAAAAGGCCCACCGGAGCGGAACAACCACGCGAGAGAACCAACGAAACCAGACACGC GACAAGAAAACAACCGAACGCCGCAAAAAAAGAGCCGAAAGCAGGCACGAACCCCGCGACACCC AGGAAAAAGCAAGGGCCCGGCAAACAGAGACGAGAAAAACGCCCGAACACGAGCGAGAACGCGG GGACCCACGAAGAAAACAAGAGCACAGAAGGCGACACGGCCAGCAACAGAGCGAACAACGAACC AAAAACCAGACAACGGAAAAGGAAGAAAGCAACAGGAAAAGGAAACAGAGAGGAAGCACAGCGA CACGAACAGAACCGAAAAGGCGACCCAAAACCGAAAAGCAAGAAAACGGGGCAAGGGGAACAAA AAGAACGCCAACCAAGGCAAGCGGGCGACCGCAAAAAAGGGGCCAAACAGCAACCGCGAGACAA CCAAGAAGAGAAAGAGACGGGCGGGAAACCCGCGAAACCGCCACGGCGAAGCGCAAACCAAAGA AGGAGACGACAAGAAGAACCGACAGGGGCGCAAGTAGAAGAGCACCCCAAAGGCGAACCCGATT CTTACAGAGACCTGCGGCCGCAGGCTAGGTGGAGGCTCAGTGATGATAAGTCTGCGATGGTGGA TGCATGTGTCATGGTCATAGCTGTTTCCTGTGTGAAATTGTTATCCGCTCAGAGGGCACAATCC TATTCCGCGCTATCCGACAATCTCCAAGACATTAGGTGGAGTTCAGTTCGGCGAGCGGAAATGG CTTACGAACGGGGCGGAGATTTCCTGGAAGATGCCAGGAAGATACTTAACAGGGAAGTGAGAGG GCCGCGGCAAAGCCGTTTTTCCATAGGCTCCGCCCCCCTGACAAGCATCACGAAATCTGACGCT CAAATCAGTGGTGGCGAAACCCGACAGGACTATAAAGATACCAGGCGTTTCCCCCTGGCGGCTC CCTCGTGCGCTCTCCTGTTCCTGCCTTTCGGTTTACCGGTGTCATTCCGCTGTTATGGCCGCGT TTGTCTCATTCCACGCCTGACACTCAGTTCCGGGTAGGCAGTTCGCTCCAAGCTGGACTGTATG CACGAACCCCCCGTTCAGTCCGACCGCTGCGCCTTATCCGGTAACTATCGTCTTGAGTCCAACC CGGAAAGACATGCAAAAGCACCACTGGCAGCAGCCACTGGTAATTGATTTAGAGGAGTTAGTCT TGAAGTCATGCGCCGGTTAAGGCTAAACTGAAAGGACAAGTTTTGGTGACTGCGCTCCTCCAAG CCAGTTACCTCGGTTCAAAGAGTTGGTAGCTCAGAGAACCTTCGAAAAACCGCCCTGCAAGGCG CTTTTTTCCTTTTc AGAG C AAG AGAT T AC G C G C AGAC C AAAAC GAT C T C AAGAAGAT C AT C T T A TTAAGTCTGACGCTCTATTCAACAAAGCCGCCGTCCATGGGTAGGGGGCTTCAAATCGTCCCCC CATACGATATAAGTTGTTACTAGTGCTTGGATTCTCACCAATAAAAAACGCCCGGCGGCAACCG AGCGTTCTGAACAAATCCAGATGGAGTTCTGAGGTCATTACTGGATCTATCAACAGGAGTCCAA GCGAGCTCGATATCAAATTACGCCCCGCCCTGCCACTCATCGCAGTACTGTTGTAATTCATTAA GCATTCTGCCGACATGGAAGCCATCACAAACGGCATGATGAACCTGAATCGCCAGCGGCATCAG CACCTTGTCGCCTTGCGTATAATATTTGCCCATGGTGAAAACGGGGGCGAAGAAGTTGTCCATA TTGGCCACGTTTAAATCAAAACTGGTGAAACTCACCCAGGGATTGGCTGAGACGAAAAACATAT TCTCAATAAACCCTTTAGGGAAATAGGCCAGGTTTTCACCGTAACACGCCACATCTTGCGAATATATGTGTAGAAACTGCCGGAAATCGTCGTGGTATTCACTCCAGAGCGATGAAAACGTTTCAGTT TGCTCATGGAAAACGGTGTAACAAGGGTGAACACTATCCCATATCACCAGCTCACCGTCTTTCA TTGCCATACGAAATTCCGGATGAGCATTCATCAGGCGGGCAAGAATGTGAATAAAGGCCGGATA AAACTTGTGCTTATTTTTCTTTACGGTCTTTAAAAAGGCCGTAATATCCAGCTGAACGGTCTGG TTATAGGTACATTGAGCAACTGACTGAAATGCCTCAAAATGTTCTTTACGATGCCATTGGGATA TATCAACGGTGGTATATCCAGTGATTTTTTTCTCCATTTTAGCTTCCTTAGCTCCTGAAAATCT CGATAACTCAAAAAATACGCCCGGTAGTGATCTTATTTCATTATGGTGAAAGTTGGAACCTCTT ACGTGCCGATCAACGTCTCATTGATACCTGAAACAAAACCCATCGTACGGCCAAGGAAGTCTCC AATAACTGTGATCCACCACAAGCGCCAGGGTTTTCCCAGTCACGACGTTGTAAAACGACGGCCA GTCATGCATAATCCGCACGCATCTGGAATAAGGAAGTGCCATTCCGCCTGACCT

[0166] SEQ 9ACTGGTCTCATTACTGCCACACACGAAACGAAAAAAGCGACCTCAGCCACACCAGGGAACGGGC GAAAGATACCCGACAAAGGCACGAAAGAGACAAATGAGGGGACAGAAAGGCGGCAGCAAGGGTC AAGGGCAACGGGCCAGAAAGCGAAGGTCGCGCGACAAGAAGCGCACGGGAAACGTGCCACCACC AAAGGGAAAAAAGAGCAATAAAGAAACCAAGAGAAGCGGGCGCCAATAGAAAAGCCAAGACGAG ACACGCCAACTACAACGAGAAGAAAACAGGCAGGAAAATCAAGCCACGAGAACGCAGAAAAAAC CATGAGGAAAGGAAAAGAAAAAACGGGGAATAAAAGAACCAGAAAGGAGACACAGGGATCCAAA ACCCGGGAGGACAAGCACCAAATAACACCACCACAAAGGAAACAGAAACATAGCACCCAAAAGA CGCAAGCACAGAAGTAGACAACAAGCCCAAACACCGACCCCATAAACAGGCCAGCCACCACCAA ACAAAATAAGAAGGAAACAAAACAGCAAAGCGCATACGCCACAGACCCAAACGGAGGAAAGATG GAAAC AAAAAC AGAG GAG AG C G GAAAT C AC AAAAC GAG C AGAC C C G G C C GAGAC T C C AAAGAC A AACAGGAAAAGGGGGAAAGGGAGCGACAAGGACAACGAAAAGAACAGGAAAAGCAAGAAGAAGG AACGGGACAGAAAGAGAAAAGCCCACGAACAACAGACGCGGGAGGAAGCACGAAGGCAGGAACA CCCGCGCCAGGAGAAAAACAAGACCGAAAAAGACCCCACAACAAAAGCGGAAGGAACAGCGCAG CCCGCACGACCAAGGCAAGAACAGCAAAACCGGGGGCACAAAAACACCGACACCCCGACGCAAC AGGAGAGCCAGAACGAAAGAAAAGAAAGGAAACGACGGACCGAAAACCAAGGACAAACAACCGA CCGAGGAAAGCACCCAACAGGAAACACGAGAGAACGGGACGAGCAGAACCGGGCACGCGGCAAGAGAGAAAAAGAAAAAGCGACGCGAAAACCAAAGAGAGACGCCAGCGCAGGCGAGCGAAAAAAAC CGACACGAGAAAAAGAAAAGCAGGCAGCACGCCCGAAAAAGGAAGGGCAGCAGCGAGAGCGACC ACCGCGAAAAAACGCACGAAGAGAGAACGAGAGGCGAACCGCCAAAAAGCGGAAAGGGAACGAA AATAGAAAGACAACACAAGGGGGGGAGCGATAACGAAACCGCCCCAGGCAACGACCGATGAAAG AAAAACAGCAAAAGCGGAAAAGTGACCGAGGGCCCGAGAACAAGCCCAACTGAACGACCAAAGC AACGAGGAAGGGCCTACACACGAGCCGACGAAACACGCCAACTGAAAACGCAGGAGCGACCACC GAGCAATAACAAACCGAACCAGAGAGGCGGAACATCCAGCAGAAAAGACACGGACACGAAGATC AGCAAAAAAAGGAAGAGGGGAGCGAATCCGACAGGGGACAACAGCCCGGCGCCATAGAAACAGGAAACCGCCAAGAAGCACATAAACCAAGACCCCACACCCCGCAAAGATAGAGCGGGGAAACAGCG AC AAAC AAC AT G G C GAAAAC AAGAAAC AAC GAG AAAAAT AC GAAAC GAAAG GAGAAC AAGAAAA AATGAAGGGAAAAAGGCCAACCCGCGCCAATCCGCCGGAACAGCAGCCAGCACCGAAGTAACAG GAC AC GAGAAC AAAG G C GAAG G T AAAC GAC AAC GAC C AC AC GAGAAAAC AT AAC AGAAAC GAC C CGAACACGAGGAGGTAAAGGCACGAAAAAACACAGACAGAAAAAGCCCACAACCGGGACAAACA ACGAGCAGAACACACGAAAAACGAAAAAACGGGCAAAACGAAGCAGGGAACCGCAAAGACACAG GAGAAAAACGACACGAACAGAGCCGAGGGCCGACGCGGGAACAAGAACAACGCACGAAGGGGAC AACCGGACCAGCAAGGAGAGAGCGGCCAACAGACACAAAGACCGAAAGAGGAAGAAACGCACGC AAAGCACGGAACGAGCACCAGCACCAGAAGAACCAGGCAAAAGAAGCAAAACGACGAAAAGCAA AAAGGAACAACGAACAGGAAGAAGGCAAGGCAGGAAAAAAGGAAAGACCAAACAGAACGCACAC CCAGAAAAGAGGGGGAGAACAGCACCCGCAAACAAACAAACAGGGCGAAAGAACAAGCCCAGAA GAGAAAAGAC AAC C AAAGAAGAAAAAGAAAC AAG C C AAAAC C AAAC GAGAAAGAAC GAC AAGAC GGGCAAAAACGCACAAGACGCGGCAAAGGCACGAGGGAAAAAGAGACACAGAAGGAAGCACACC AACCAAGCAGCGCAAGACCACAAAAGTGCGACGGGGCGGAACAACACGGCAAGATAAACGGGCA CAGACGGAACGAAAACGCTAAACGCCAACACGCAGCCCAAAGGACATCGAGCAGAGAACACAGA AAAAAAGGCATAAAAACGCCACCAACAGCCAGAAGGCCTAGAAAAGCACAGACAGAAGCGGACA GCTAGGAGAACCCAGGCACGAAAACCAGGGTCGAGAGGAAAGGGGGGCGAAGAGAGGGTAAAGG AGAACCAGGACCAACCCAAAAATCCCAGCCGACAACGAGCAACAGAGAGCTACCCGAACGCCGG C AAAC GAC C AAAAG TAG C AAG C AC AC AC AAC AAAAAC AC AGAT C CAAGAAGAAC AAAAC AG C C G GAAGAATCGAAAAAGCCGCCCGCAGCCCACGAGGTACAACACGACAAACCAAGCAAGCGAACTA GACAGGGAACACAAAAACAAAGAGAGTCACCGCGAAAACAACGCAACAAAGGGATGGGACGAAA CCCGGACAGAGACGAGCCTAAAAACAACGGGGGCGAACACGAACAATGCCCCACGAGAACAGCA CACAAGGCAATGCAGGAAGCACAAAAAAGAACCCCCAATACACCAAGAGAGACAAAGCGGAGCC ACAGCCGCGGCGAGCCGGCAAAGCACCGACAAAGAACACCAACACCACGAAGAACCAAGGCACA CCAGGAAAACGAGAAAGCACAGCAGGGCGGAACGAACCGAAAGGCAAACGAGGAAACAACAAAG CGGACACGCAAAACCCCAACGCACCCGGAGAACGGAAACAAGCCCCACCAGAAACAAAGCGACA AGAGCCAGGCAAACAAGAAGAAAGAAGAAAAGGAGGGCGCGACAACACCCGGGAAAGAAAAACG GGGCAAAGGGAACAAACAAACAAGCGGGCAGAGCGCGCAACAAACAGAAAGAGGGGCCAAAAAA GCAGCAGAGAACAGGAAAGCGCCCACCCCAGAAAAAACGAAGAAACAAAAACAAAGAGCGCACC ACGAACGGCCCAAAAGAAGAAACGACACCCACGCAAGCCAAAAACCCACCCAGCAGCCGCGGGG AAACGAACAAAACGAGGGGCAACGCACAGGCAACGAAAACCACACCGCACCAGACAAGGAGCGG CAACCCGAGAAGCCACGAGAGAGAAGGGCACAGGAAGGGCAGGGAAACGATAGGGCACACAGAA AGCAAGAACAAAACTGAAGGGACGACAAGGCAGAACCAAACGTACCCAACCGCAGAAAAAAACG CCGCCGTAAGCAGAGAAGGCGCACGACAAAGGCATAACAAGGAACGGCAGAGCCGGACAGAATC GCGACACGGAAACGAGCGCGAAGGGATCAACACGGCGCCAGACAAACGGGAAAGTAACGAAAAGGAAAGAACAGCAACACCATGCCCAAGCCCACGCCCGCGCAGACAAGTCAAAAAGAGAGGAGCAG AGCACCGAAATAAAGGCCACCCCCACCCACAAAGGGCATACAAACCGAACAAACAAAAAGAGGC CATGCGAGAAACAAAACGAGAGAAAGAGAATCAAAGGAACAGAAAGGCCAGCAAAAGATCGGAA ACACCCACAGAGACGCGAAAAATCGCCACAAACCAGGGAAGAAACAGCCGTACCAGACAAAGCA AACACAAAAAACCATGAAACGAAAGGCCAACCCGAAAACACATAAAAAGAGACAGAACGAGGGG GAAGAATGGCCAGCAGGGACGAAAGGAACGAAACTAGAAACGGAGCGACGAGCACACGCCAATA GACCAACCGCACAGCAAGAGCAAAGAAACGAGAGCGCAGGGGGCCGGCCGGCAACCCGACAGCA C C C AAGAGAGAGAAC C AC AGAAGAAAC AAAAC G GAAG C GAG GAG C GAG C GAG AAAGAAAAC AGA GCGGGGCCCACAACGCCAGACCACAGCCAACCGGCAGCAACGGAAGCCACCGGACACGAAGGAC CAAGCAACAAGGAGACAAGCCCAAAACGCAACCAACCGCCGCAAAACAGGAAGGAAAACGGCCC AAAGCAAAAACAAAGAAAAAGACGGAACGAGCGCGCAAAAGCACCACAAGCAGGCCAGACGAAA AACAAAACGGGACAAAGAAAGGCACCAACCGCAGACACCAAGACACACGAAGGCCAAGAAGAAC CGAGCGCACACAACAGGAAAAAACAGGACCGAAAAACCAGAGACGAGCAAAACGGACAGAGAAC AGCGAGCGGGCGGGACAGCGCAGCGAGCCGAGAAGAGACACCCACCAGGAAAAAAGGAAACACA ACCCAGAGAAAAAACAAAAGAGCGAAACCAAGGCAAGAGGCCAACCGGAAAACGGAAGGAAGAA AAAAACGAGCTGACCCGGCGAAACCCACGAGAGAACACTACGCAGACAACAGACGAAGGGAGCC AGTAGACGAACAGGGGGCAGGAACAAAAGCTAAACAAGCAGACGCGAAAGACAAGAACTAAAAG GAACCCAGCCGGAAAAGGGAAGTCAAGAAAAAGAAAAACAGAAAAAAGAATGAGCCCAGACAAA GAG C GAG C C G G GAG T AGAAGAAC C AAC GAGAG GAG C AAC AC C T AC AGAAAGAAAC G C AC GAAAC ACGGGCTGCGAAACGGACGACAAACAAAAAAGGATAGACCAGCCCCGCGCAACCAGAGCGGATA CGGCCCAAAAGGAGAAACCGCGAGGGTAAGCAACGAAGCGCACGAGAAGGACACTGAAGCCCCC C C GAAAAC C AAC C AC C AC T GAC C AC GAAAAAAAG C AAAG C C GAC C C T AGAAAAC AAC G C AGAC G ACAGCGGAGATGGGACCACGCCAAGAACACACAGACAATCGAAAAAAACAAGGCAAGAGGAGAA GAT GAC AAAAAC AGAAAAGAG G C AC G C AAC T AAGAAC AGAC AAAAGAAC GAC GAC AAC T GAGAA AACCGCCAGCGAAGGAACAGGCTCCACCAAGAGAAAACAGAGGGACGAACGGGCAGCGAAACAA GAAGCCGCCGGACAGACACAGACCCCAGAAAAGCGGAAAAGAAGCAAGGGACGAACAACACAGG AACAGAAAAGCAGGCGGGCCCGGACCGACCACCGCCGAAGAAACAACAAAACCAAAAGCGAAAA AACCAAAAACGAAAGACCAAACCAAGAAGGGCCCCAGCCCGAAGGCAGCGCCAACAGGAGCAAA AAACAAAACGCAAAGAAGCCAGCACGCAACAGGGCAAACGCCGAAGCGGCGACGCCGCAAAAAA GACACGCCCGGACGAAGCAACCGCAGAGGGAGAAACCAGAAAAGCAGAAACAAGCACCCCGACG AAAGAGAACGAGCGAGGAAACAGAGCAAGAAGCCGACAAAGCAAAACAGGGCAGAGAAAGCAGG C C GAAC C GAAAAC G GAC C C G GAAAAAAC C AGAC C AGAAAAGAAAAAAAC C AAAAAGAGAAAGAG AGACAAAAAACCGGCGGCACCACCCAGGAACCGAAAACAGGAACAAAAACGAAAGACACACGAA CAGAAACAGACAGCGGGGAAAAAACAAGCGGAAATAGAAGAGCCCAAACCCAGAAGGAAAAATT CCAGAAGAGACCTGCGGCCGCAGGCTAGGTGGAGGCTCAGTGATGATAAGTCTGCGATGGTGGATGCATGTGTCATGGTCATAGCTGTTTCCTGTGTGAAATTGTTATCCGCTCAGAGGGCACAATCC TATTCCGCGCTATCCGACAATCTCCAAGACATTAGGTGGAGTTCAGTTCGGCGAGCGGAAATGG CTTACGAACGGGGCGGAGATTTCCTGGAAGATGCCAGGAAGATACTTAACAGGGAAGTGAGAGG GCCGCGGCAAAGCCGTTTTTCCATAGGCTCCGCCCCCCTGACAAGCATCACGAAATCTGACGCT CAAATCAGTGGTGGCGAAACCCGACAGGACTATAAAGATACCAGGCGTTTCCCCCTGGCGGCTC CCTCGTGCGCTCTCCTGTTCCTGCCTTTCGGTTTACCGGTGTCATTCCGCTGTTATGGCCGCGT TTGTCTCATTCCACGCCTGACACTCAGTTCCGGGTAGGCAGTTCGCTCCAAGCTGGACTGTATG CACGAACCCCCCGTTCAGTCCGACCGCTGCGCCTTATCCGGTAACTATCGTCTTGAGTCCAACC CGGAAAGACATGCAAAAGCACCACTGGCAGCAGCCACTGGTAATTGATTTAGAGGAGTTAGTCT TGAAGTCATGCGCCGGTTAAGGCTAAACTGAAAGGACAAGTTTTGGTGACTGCGCTCCTCCAAG CCAGTTACCTCGGTTCAAAGAGTTGGTAGCTCAGAGAACCTTCGAAAAACCGCCCTGCAAGGCGGT T T T T TCGT T T T c AGAGC AAG AGAT T AC G C G C AGAC C AAAAC GAT C T C AAGAAGAT C AT C T T A TTAAGTCTGACGCTCTATTCAACAAAGCCGCCGTCCATGGGTAGGGGGCTTCAAATCGTCCCCC CATACGATATAAGTTGTTACTAGTGCTTGGATTCTCACCAATAAAAAACGCCCGGCGGCAACCG AGCGTTCTGAACAAATCCAGATGGAGTTCTGAGGTCATTACTGGATCTATCAACAGGAGTCCAA GCGAGCTCGATATCAAATTACGCCCCGCCCTGCCACTCATCGCAGTACTGTTGTAATTCATTAA GCATTCTGCCGACATGGAAGCCATCACAAACGGCATGATGAACCTGAATCGCCAGCGGCATCAG CACCTTGTCGCCTTGCGTATAATATTTGCCCATGGTGAAAACGGGGGCGAAGAAGTTGTCCATA TTGGCCACGTTTAAATCAAAACTGGTGAAACTCACCCAGGGATTGGCTGAGACGAAAAACATAT TCTCAATAAACCCTTTAGGGAAATAGGCCAGGTTTTCACCGTAACACGCCACATCTTGCGAATA TATGTGTAGAAACTGCCGGAAATCGTCGTGGTATTCACTCCAGAGCGATGAAAACGTTTCAGTT TGCTCATGGAAAACGGTGTAACAAGGGTGAACACTATCCCATATCACCAGCTCACCGTCTTTCA TTGCCATACGAAATTCCGGATGAGCATTCATCAGGCGGGCAAGAATGTGAATAAAGGCCGGATA AAACTTGTGCTTATTTTTCTTTACGGTCTTTAAAAAGGCCGTAATATCCAGCTGAACGGTCTGG TTATAGGTACATTGAGCAACTGACTGAAATGCCTCAAAATGTTCTTTACGATGCCATTGGGATA TATCAACGGTGGTATATCCAGTGATTTTTTTCTCCATTTTAGCTTCCTTAGCTCCTGAAAATCT CGATAACTCAAAAAATACGCCCGGTAGTGATCTTATTTCATTATGGTGAAAGTTGGAACCTCTT ACGTGCCGATCAACGTCTCATTGATACCTGAAACAAAACCCATCGTACGGCCAAGGAAGTCTCC AATAACTGTGATCCACCACAAGCGCCAGGGTTTTCCCAGTCACGACGTTGTAAAACGACGGCCA GTCATGCATAATCCGCACGCATCTGGAATAAGGAAGTGCCATTCCGCCTGACCT

[0167] SEQ 10CAGAGCGGCCGCAGGCTAGGTGGAGGCTCAGTGATGATAAGTCTGCGATGGTGGATGCATGTGT CATGGTCATAGCTGTTTCCTGTGTGAAATTGTTATCCGCTCAGAGGGCACAATCCTATTCCGCG CTATCCGACAATCTCCAAGACATTAGGTGGAGTTCAGTTCGGCGAGCGGAAATGGCTTACGAAC GGGGCGGAGATTTCCTGGAAGATGCCAGGAAGATACTTAACAGGGAAGTGAGAGGGCCGCGGCAAAGCCGTTTTTCCATAGGCTCCGCCCCCCTGACAAGCATCACGAAATCTGACGCTCAAATCAGT GGTGGCGAAACCCGACAGGACTATAAAGATACCAGGCGTTTCCCCCTGGCGGCTCCCTCGTGCG CTCTCCTGTTCCTGCCTTTCGGTTTACCGGTGTCATTCCGCTGTTATGGCCGCGTTTGTCTCAT TCCACGCCTGACACTCAGTTCCGGGTAGGCAGTTCGCTCCAAGCTGGACTGTATGCACGAACCC CCCGTTCAGTCCGACCGCTGCGCCTTATCCGGTAACTATCGTCTTGAGTCCAACCCGGAAAGAC ATGCAAAAGCACCACTGGCAGCAGCCACTGGTAATTGATTTAGAGGAGTTAGTCTTGAAGTCAT GCGCCGGTTAAGGCTAAACTGAAAGGACAAGTTTTGGTGACTGCGCTCCTCCAAGCCAGTTACC TCGGTTCAAAGAGTTGGTAGCTCAGAGAACCTTCGAAAAACCGCCCTGCAAGGCGGTTTTTTCG T T T T C AGAG C AAGAGAT T AC G C G C AGAC C AAAAC GAT C T C AAGAAGAT C AT C T T AT T AAG T C T G ACGCTCTATTCAACAAAGCCGCCGTCCCGTCAAGTCAGCGTAAATGGGTAGGGGGCTTCAAATC GTCCGCTCTGC GAG T G T TAG AAG C AAT T AAG AAAT T C T GAT T AGAAAAAC T C AT C GAG CAT C AA AT GAAAC T G C AAT TTATTCATAT C AG GAT TAT C AAT AC CATATTTTT GAAAAAG CCGTTTCTGT AATGAAGGAGAAAACTCACCGAGGCAGTTCCATAGGATGGCAAGATCCTGGTATCGGTCTGCGA T T C C GAC T C G T C C AAC AT C AAT AC AAC C T AT T AAT T T C C C C T C G T C AAAAAT AAG G T T AT C AAG TGAGAAATCACCATGAGTGACGACTGAATCCGGTGAGAATGGCAAAAGCTTATGCATTTCTTTC CAGACTTGTTCAACAGGCCAGCCATTACGCTCGTCATCAAAATCACTCGCATCAACCAAACCGT TATTCATTCGTGATTGCGCCTGAGCGAGACGAAATACGCGATCGCTGTTAAAAGGACAATTACA AACAGGAATCGAATGCAACCGGCGCAGGAACACTGCCAGCGCATCAACAATATTTTCACCTGAA TCAGGATATTCTTCTAATACCTGGAATGCTGTTTTCCCGGGGATCGCAGTGGTGAGTAACCATG CATCATCAGGAGTACGGATAAAATGCTTGATGGTCGGAAGAGGCATAAATTCCGTCAGCCAGTT T AG T C T GAC CATCTCATCTG T AAC AT C AT T G G C AAC GCTACCTTTGCCATGTTT C AGAAAC AAC TCTGGCGCATCGGGCTTCCCATACAATCGATAGATTGTCGCACCTGATTGCCCGACATTATCGC GAGCCCATTTATACCCATATAAATCAGCATCCATGTTGGAATTTAATCGCGGCCTCGAGCAAGA CGTTTCCCGTTGAATATGGCTCATAACACCCCTTGTATTACTGTTTATGTAAGCAGACAGTTTT ATTGTTCATGATGATATATTTTTATCTTGTG C AAT G T AAC AT C AGAGAT T T T GAGAC AC AAC G T GGCTTTCCCCCGCCGCTCTAGAACTAGTGGATCCAAATAAAACGAAAGGCTCAGTCGAAAGACT GGGCCTTTCGTTTTATCTGTTGTTTGTCGCATTATACGAGACGTCCAGGTTGGGATACCTGAAA CAAAACCCATCGTACGGCCAAGGAAGTCTCCAATAACTGTGATCCACCACAAGCGCCAGGGTTT TCCCAGTCACGACGTTGTAAAACGACGGCCAGTCATGCATAATCCGCACGCATCTGGAATAAGG AAGTGCCATTCCGCCTGACCTTGCCGGGAGCAGAAAGAACGAAAGAACCTCAGCCAACCGAAAC AGGCCGCGAGCCCTGAAAAAGCAGGGCAAAGGAGAGCCCGCTACAACCAAAACGGAAAAAAGAG GCAAGTACCCGAGCAGAGGAGCAAAAACGCAACTAAGGAGGAAGGGACCGAAACAACGAGGTAA CGCAAGAAGCAGAAGCGAGGGCACATAAAACCCCACAAGACAAGCCCGGAAAGTACAAAAAGCG AAAAAAAGGAAGCCCAATAAAAGACAACGGGAGACGCAACAAAGATCACAGAGCCAGACAACGA AAAGAAAAATAGCGCCGGAACAAAAAAAGGCGAGAACTGAACCCAAGAACCACAGAAGCACAGGATGAAAACACAGGACCACGGCAACGCAGCTGAAAAAAACAAAAACGCGAGAAAACAATAGAAAACCCAAAACAGACCCGGGCAGATAGAAAAGAACAACACGAAAAACCCAGCTAGAAACAACAAGGGAGGGCACAAAAAGTAAAACCCAAGAGAGAAGGAAGAAAAAGTGCAAGCCCCCCGACCGCCCACAAAAAATCAGAAACAACAAACAGGGCACCAGGAATGAGCAAGCGGAAGAAAAGGACCAAAAATAGAGGGAAGGGAAAGCCCGAAGGCAGGACAAAAGAAAACGACGACCAACCCAACAAAGAAAAGCAAACAAAAGACGCAAAGCGGAAACCACCGACAACCGAACAAGAACAGGCACAGACGAACCGGCGCGCACAGCAAAAACCAGGACCCGAAAGAACGCCACGGAAACCAGAACCCGAAGGGCGCAGCCGGCCCCAAAAGAGAGCCGAAAGACGAACAAACGAGAAAGGAAACACAAAGGCACCAAAAAAGCACCACCGAAGAAAGCGCAACCGAAGAAAAGACCCCCGCAGACGAAACCGAAGCCGAACAGGGGCAACGGAGGAAAAAGCAAACGACAGGCGCGCACCGACGGGGGCAACAAGCCAGCGCAGCAGCACAAAGAGAGAGAAAAACGGGACGAGACAAGACAGAAAGAGCACACAAAAAAGACAAGCCGCCAAGGGCGCCAAACAAGACAGGAGGGACAACGGACAAAAAACCAAAGGCCAGGGGAGCAAAAGAAAGAGGCAGGCAAGCAAACACGCACCGGCACCAAAAAGGAGCGAAACGCAAAAACGAAGCGAAACGGGCAAGAACAGAGACAATAGAAGGCGACAAAAAGCACAAGAAGAGTACGGGAGAGGCCGCGCCAAACAACACCTACAAACCAAGAACGAGCAACAACGAAATGAGGGGCAGCACAAACGCAGGGGGCGCTAGAACAAGAGGACCGGGCCGCAAACACTCCCAGACAAAGAAGGAGCGACGCAGAGTAAAAACGGAACACACACAAGAACAGCCTGAAAGGCAGCGCGAGAAAGCCACACGATAAAAAAGAGGAGAAAGACCAACGAACATAGCAGCGGAAAAGCAGGCCCCGAACCGTAAACCACCGAAGGGAGCAACGAGACAATAGGAACAAAAAACCAGCAAGCAGGAAATAGCCAAAACCAGCCGAAGCAGGAACAGTCCCAAAACGCACACGAAAGCACAACGCTGCCACCGGGAACACCACCAGGCCAGGCTAAAGGAAAAGAAACCGAAGGGCGGAAGTGAACAACGGGCACGCCACAAGAAAGACTAACCAAAGACAACAAAGAACGAAGGAATACAAACAAAAGACGAAGGAACGAAAGATACAGGAGGAACAACAAACAGCAAGAAGTAAGAAACCAGAAGGACGGCAGAACCAGTGAAGGACCAAAAACAGGGCACAGAAGCGGAAGGAAAAGGCAGCACGCACCAAAACGCAACAACCCAGACGAGAAGGGCCAAGCACAAACGAAACGACCGAAGGCGAGGAAGAAGGGAAACGAGAAAAGAACCAAGGGAAAAAGGAGAAACAGAAGCCGCCAAGCCAGGAGAAAGGGCGGACCACGACCCGGGGAGGAACAGAAGAAAACAAACAAAAAACACGCACGCACCAAGAACACCCAGAGAAAAAGAACAAAGCCACGCGGGAAACCGCAACAGACAAGGACAAACGACCACACAAGGCAGACAGCGACAACCAAAAAGAGAAAGGAAGAAACAAGGAAGCAAAGGGCGGACGAAGAACGCACACGAACAAACCGACAGCACAAAAACCGCGCAGGCGACCGCAACCCGCAAAAGACCGGAGAGACGCACGGCCAGCAGGCAACAGCGGCAGGAGAACAAACAAAACGGACAAAAGGCAGCGCCGGAAAGAAAGGACAAAAAAGCAGACGCCCAAACGCAAAACCAAAGCAAACCACACAAAAAACACGCACGGAAGGGAAAAAGGAACCCAAAAAGAAAACTCGAGAAAGGAAAACCAGGACGAAGGCATAACACCGGAGGCGAAGAGGCAAAACGGTCAAGAAAAACAAAAAGGGAAAGAAGCCTAGCGAAGCAAGGGAAGAAAGCAAAAAGTCCACACACGCGGGGAAAAAGGACCGACTCGAAGGCAACAAGGGAAACGCGAACGATGACCGAAAAAAGAAACCCGCAGGACAATACGCCAGCCAACCGGAACGGAAGAAACTAACGACAACGAGAGGACACGAGAACCGTACAGGGCAGGCGCAAACCAAACCGCCATAAGCAC CAGACGACGAAGGGGCAAAAGTGCGGAAACGAAACCAAAAGAGGCGAAATACAACCCAAAAACC GACCAACCACACATCCAAGGAAGGGGGGAAAACGAAACGAGTAAGCAAAAAACCGGCAAGCACG CGGAATGAAACGAAGAACACAGAAGGCGGCAGCTGACGCCAAAGCGGCAACAAAACAAACATCA ACGGCAGGAACGAGAGGGAGAAACATAACAACCCAAAAAGGAGACGAACAAAATCGCACCCAAA CAGCGCCGAGGACAACATGAAAAGGCGAGCAAGCGGCACACGGGATACGAAGCCGGACCAGAGA AG G C AAGAAG C GAG C AGAAAC AAAAGAAC G C C GAAAC AGAC AAAC AAGAAAC AGAC AAC AAAAA CACAAGGCGACGAGAAAAGCGCAAAGAAGCAAAACCGCGCCAGCAAAAAAGCAAGGAACCCCCG GAGGAGGGGCGCACGAGCGAGAACAGCACAGAGGAGCGAGCGAAGAAACCAAGAAAAAGCAGAA CAACCAGGACGAAAACAACACGAAACGCAGAGGCAAAAGCCCAAGACGACAGCGAGAGCAGCAG AAGCAGAAAAAGAGGCAAGACCAAACAAAGGGGGGAGAGCCGAGGGGAAGAGAACGAAAGACGC AAGGAAGGAAAGAAAGCCCAAAACACAACACCGCCAACGCACGACGAAACCAAAACAGACAGGA AAACGACGGAACAGAGCAAGAGCCCCCCGGCGGAGAGAAAACAGAAGAACAAAAGCCAGAGAGC AAAAGAGGAAGAAAGCAACAAGCAAAGGGAACAACACAGAAACGACACGGCAGGAAGAAAAACC AAAAACAGAAAAAAAGGCACAAGGAGGACGGAGAACGACGAAAAGACGCGCAGCGGATACACAA ACCACACACCCCGGGCGGCAGTGAAAGGAACACAAAAAGACCCGACACCTCCACGCGCGGAAAG CCAGACAACCAAATCAGCAAACAACAGCAGGAGAAGGAAAATAGAAAAAGAACCAAGAAAACAA AGCCATCGAAACGGGAAGCCCAGAAGAACAAACTGAAGAAGAAAAGCAGACACAAAAAAGGTAA CAAAAGAAAAGGCCAACAGCAGGAGTCCCAACGACCCAACACCCCCGCGGACATAGCAGCGAAG GCAAGAAAGGGACAAAATAGGAACGAACGACACACAAGGAGAACGTCAAAAAAGGGCGAGGCAA GAGCAACAATCCAAGGAACCGAGCGGAGAAAACGCAATAGACAAAGCACGAAACACAACAGCAA ATCACCCAGAAACGACCAAAGACAAGGGATGAGGAACACAAAAAAAGCCCCAAAGACTGCGAAA GGACAAGGGGAAGAACCAAAATAAAAGGGCAGAAACGCAAACCACCCCCTCCAAGAGAGGGAAC ACACACCAGGGAATCCGGGGAAAACGACGAAAACAGACGGCTAACAGGAGAAAAAAAGCGGCAG CAGACTCCCCGCGGAAAAAACAGGCGGCCAAACGAGCGCGAGAAAGCAACCGAGCACGACGGCC AAGCAAAGAGCCAAAAAAGCAACCAAAGAAACGAAGGCGGCAAAAAAAGACAAGAACGCAAGGA AC AAC C AAAAC AAAC AC C AAAG G C AAGAAAAC AAAGAGAG C GAAC AGAC G GAGAC G GAC C AC C C GACGAAAAGGAACAAGGACACAAAGAGCAGGCAAGAACAACACCACGACAGACGAAAAAACCCC ACAGAAAAAGAGCGAAAGCAAACCCAAGACACGGGGGAGGACGCCAGAGAAACGGACGGACCGA AAACCAGCGGACCGCAGACAAGGAAACAGACAGAAAAGACGCGACCAAGACACGAGAGGGGAAC AAACACCGACCGAAAACAAGGAAGAGAGCAGACAGAAGGAAAAGGAAAAGGAAACGAGAAAACC CAAACCAACGGGCCGCAACCAAGGGAGCCGGGAACAGGACAACCCAAAGACAGAACACAAGAGC AGACCGAAAAAAGGCAACGAACAAAGGCAAACGAACAACGGGGACGGAAAGCGAAAAAAGCGCC GGCCCAAAAACCAGCACTGACGAACCGAGCCACCACACCAACAAGTCGCGAGCCAAAACACAAG AACCAGAAATAACCGGAAACACACGACCGGGAAGAAATCAGAAGGAGGGACAAGGAGGACGGAAATACACGCGGGGGGAAAACCACGAGGCGATAACAGACCAAGCACGAACACCAAACCATCCAGAA GCAGAGGAGGCCGGACGCCCATACCGCAACGAGCCAGAGAAAAGACCAATGAGAACAGAAAACA AAGACACGAAAAGTCGACAGGAAGAAGCGGCAAAACAGACCTCAGAAAAGAGACAAAGCAAACC CCAACTGAGGGGGACGGGGGGAGGCCGGCACAGTAAGAACGCCAGACAAAGAACAAAAAAATCC GACCAACAACACCCAACAACGGAAATAACGCACAACACCCCAGAAACAGAACATGCCGGCGAGG CCAAAAACACCACGCGATAACCAAACAGGAAAGGAAGAACCAAACTCACACGCCACAGCAAGAG AAAAGGAAATAAAAGCGACGAGCCACGGGCCAGACACTAAGCAACGACAAAAGCAAGCAAGACC GTGAAGGGACAGGAAGGAGAAACACAAGGTAAAAGACGACGCGAGGAACCACAAAGAGCACAAC AAAAGGGCAACAAACAGAGCAAACGCACCCAGAGCGAACCGCACACGGCGAAACGGAACACAAC GCCGAGAACAGAAGCGAGCAACACAGAAAACAAACAGCGGAAGGAGCAAACCGCAGAACCCGGG CGACCAAGAAGAGAAAAAGGCGAGCCGAAGAAACAGGAAAGCCGACCAAAGGCGACGAAACAAG AGCCAGAAAGAAACACACAAACAAAACCCACCACAACGGACACAAAACAGGACCAAGGCAGAAA CCACAAGGACGCAAGGACGAAACCCCGCAACAAGAGACGCCGGGAGAAAAGAAAGAAAGGAAAA AGAACGACAAACACCGAGGGGCCAGGAAAAACAAAGACAGAAAACAACGGCCACCCAAAGAACA ACACACAGGCGCCGCGAAACACAACAACGACGAAGAAAAGCGAAAAAGCACAGGCAAGCGCAGG AACGCACCCAGACAACAAAACACCAAACGAGGAAAACAGAGCCACGGACAAGCGAACAAACGCA CCAAAAGACAACGCCCAAGGAAAAAGCACCAGGCGGAAAAATAGAAGAGCCGAAAGGGCGAAAC AAGAATTCGCAATGCCAAACCACCGGCCAGGAAGAAGCCCTCAGCACAGGCCCAACAAGACAGG C GAAT C GAGAC GAAGAAG C AAC GAAC G G G C AAT C GAGAGAAAC AAAAAGAAAAAAGAAC AT GAG ACGAAGCAACAGGAGCGAAAAAAGTGGCCAAAAGCAAAACCCCAACAAGCAATGAAGGAGAACG AGAGCAAAAGAAAGACTGGCCGCGGCGACACGAGACGCGACCAGTGCCAGAGAGGGAGCCGACA AGCGGACGTGCCCAAAAGACACACGCAAGAGAGAAATGGCCGAAAAAAGCAACAGCCAGACCGG TGCAAACCGGCAACGGGCGAAAGGACGATGCACACGGCCGACAGAAAACGGAGGACTACGGCAA GCGAAACACCGAGCAGCGACTCCGAAAACAAAGCGCGCAAGAGAACACTGGACAAAAGACCAGG AAAGCAAAGGAGTACAACAAGGGAGCCAAAAAAAGAAAACTAGGCAAAGGGGCAAGACCCAAAC CAACTGGGCAAAAAAGGGAAAAAGGAAAAGAATACGCGCAACCGGACGGAGCCAGACCCCTACC GCGGACGCACGGAGGCACAGAACGTGACACAACAAACAAGCACGGCAAAGAGTAAAAGCGAAAC GCGCAAGGGCAACGCAACCGCAAGGGGGAGGCCGGAAAACAGAAGAACACGGGAGCAAAGAGGC CGCAAAACGGCAAGGGGAGGACCGGAGCCGAAAAGCCCGGAACACCCGAAGAAAGCGGACGACG AAAC GAGAAC C C AAGAAAAAG G GAG GAAC C C C C AAG C GAAAAAC AC G C C AC AAC AAC C AC AGAG ACAGACCGCAGACCAACACAACAAAGACAGACGCGAAACCCCGAAGCCGAGAAGAAAAGCGCCA CAACAAAGGGAGAAACAAAGGACACGCGAGACAAGCGAACAGAAACGACCCCAACAGCGCGAGA GACAAAAAAGGAACGGGCCAAAACACCCGAAAAGCCCAGAAAACACGGAAGCCGGCACGAGAAA ACAGGGGAACCAACCAGAACAACCGAAAAAAGCGGAACAGACAGAGAAACAACAAAGAAAAAAG CAGAGAAAGCAAAGACAGCAACGACCGCGAGACGCAAAAACGAGCCAAGAGGAACCACACGGACAACGGGCGAAAAAACCACGACACGAGAGAGGACGGAGCGGGAAGCAACGCAAAAAGCAAAGACA TAGACAGGCGAAACCACCAACAGCACCATACCGGCCAGAAAACCGAAGGGCAAAGGTCGCGAAA ACGAACAAAGGGACAACAGCTAGACGAGCAAAACGGAAACAAAAAACCTAAGCAAACAACCAAC AAGACAGCAAAATAGAAGAAACCGGGCGACAGCGAAGGGATACAAGGACACAGCAGAGACAGGG CAACTCAACGAACGCCGAAAAAGAGGGCAGAATAACGAAGAGAAAGGGGCCGAAAACAACTAAC GAG C GAAC GAAAG C GAG AC C AG AAT AAC GAG GAG AAC AAC AAAGAAAAGAGAT AGAAAG G G GAA GAGAGAAACAAACGGCTCGCAAGGAGGCCGGACGCAGCAGCGGCTAGCAAAGCCAAAGCAAGAC AGCGCAGATGAAGGACAAACAGGGCAAGCAAACAAATAGCAGAAGGAAAAGACAAGCCCAAAAA TGACACAGACCGCAACAAGCGACAACAGTACAGCGGACCGAACAAGCGCCAGAACATCGAACAG AGAGAAGGGCACGAAACAAATACCGAAACCGGAGGGAACAGAGAAGAATAAACAACAGCGCAAA GAAACGAGGAACTGAAAGGCGGGGGGAAAAAGCGCGCAGGAAAGACGCCCACAAACCAAAGAAA CCAGGAAACCGCAAGAGGGGCAAAAGAGCAACGAAAAACAGAAGGACAAGAAGCAAGACAGGAC GACGACCAGACCAGCCAAAAAGAGCAGGAGAAGAGAAGCGGGGGCAAGAAGCAAACCACAGGAG CGCAGGCGCACAAGGCCACCACCCCCCCAGAAACCAAAGACGGCACAAAAAGAAGGGAAAACCA AACCCAAAACGCAACAAGAGAAGGGGCGACAACGGAGCGAGAAACGAAAGGCCCAGAAAAAAGC CAAAGGCACAAGGAGAAGGCAGAAACCAAAAGAAAACGACAACAGAGGGAGAGGAGAACACAAC GCAAGCAAACCGAGAAAAAACAGACCAACAAACCAAAAAAAGAAAAAGGAACAGGCCAGCCCGA AAAAC AAAAAGAGAAAAGAC C C C GAGAC AAC AAC C AAGAAAC AC G GAGAC AAAAGAC AAAC G GA GGAAAGGAACAGCCGGGAGCAAACAAGAAAAACCACAAGAACAGGCGGACGAAACGGCCAAAAG ACGGAAAAGCCAAAAGGAGGGGAGTACAAAAAACGACACGCAAAAAACAGGATAGCACAAGGGG CAGACCACAGGAACCGTGGCGAAGCGGCAGCGAGAAGGCGGCACTAAAAAGCAACAGCAGGACA AGGACGCATAGAAGCGGAAGCGGAGGAAAGAGAAAGTCGAAGCCCCGGCAACCAACGAGGCAGA TACGACAAAGCAAGCCACGAACGAACCGTCCGGACAAGCAGGAAAGCGACGAGCAGTAGGACGA AAAACGCAAAGCAAAGCGACTCCAAAGCAAGAAAACGAGAACCAGGGCTGAAACCAACAGAGAC AAC AAAC AG C AG T C AC C AGAAC AAGAC AAAC AGAAAC AC C T AGAAAAC C G GAAC C GAG C AC C GA GGACTAAAAGACGAGGGCAGACCAAGAAAACATCGAGAAAACACAAAAAGAAAACGAGCCTGCG AAAC AGAAAC AG C C GAGAAAC G AC T AAAC G GAAC GAC C AG GAC GAAAAG GAG T AAAGAAAAAGA ACCACCGGAGAGCAACTACCACAGGAAGAAGGACGAAAGACGGATCACGGAAGGACAGAGGGGA GAAC C G GAT G GAAC AGAGAAAG AAGAGAAC AAAAAAT AGAAAAAC C AAC C AC AC AC AC GAG GAA AAGAGAAAGGGAAAAGGCGAAAGCCCGAAAACGGCAAAGACCCAAGCCGAAAACGAGGAAACCC AAAAGACGAAACAGGAACCAACCAAGAACAACGGGCAAACAAGAGACGAGAAAAAAGCAAGGAA CAAAGAAAACCCACACCAGAAAAAGGCACAACAGAAGCGGGCCCCAGACAAAAACAGGACGAAA AAAAGCAGAAGGACACCGCAAAGCCAGACGAGGAAAGGGAAACCAAAAACGAAAAAAAGGGAGG CAGGACGGGCCGGAAGCAGAAAAGAACAACAAAGAAGGAACAGAGGAGAGCAACCAGAACAAAG GAACGGCGGAGAGGACAGCCCAACCACGACACCAGGCGCACGAACAAGAGCGCCGAAGCACGACAGGGCACCAGAGGACGAACAGCAGAAGAAAAGACGGGCGAGAGAGCACGCGACAAAAACAGAAG AAAAAAAG C AAAGAC C AAAGAAAC AAAAAAGAAAC G C GAGAAAAAAGAC C AAC C GAG GAG GAGA ACAAAGAAGGAGCAGGCAACAGCACAACAGCAAGAAAAGACGACAAACTCACCGGGGACCGAAG GACCGAAACGCATACAGAAGGAAAGCAACCAGGCGCGGCATGAACACAAAACGGGACAGCACAG CGAGTAGGCCGCAAAACCGCAGAGCCCACAGATGGGAAAGCACGAAGCAACAGACCAACATAAA ACAGAAAGGCGAAACACAGAAGCATCGAACAGCCACAGCAAACCAAAGGACATGCCCGCAGGGA GCAAGGCCGCGAGGAGTAAAAGAGCAGAAAAACAGGCGAAGGAGTAGGAGCAAACCAGCCAAGA GAAAG GAG T G C AAG GAAAAGAG C AAC AC AAGAAGAAT AC C AAAAG C GAAC AAC AAC GAC AC GAG TGCAGCAAAAGAAGGGCCAAGACACAACTACAAGGACAAGAACAAGAGCGCAAGGGTCAGAAAA CCCAACGACAACAGGCGAAGTACAGAACGAAACGACAGCCCACACCAGTCAAGGGAGAACCAAC AACCAGAAAACCTGGCGCAAACCAGCACCGAGAAGAAACATGGACAGAACGACGAGGGGAAACC AAGCTAAACGACACGCACGGCACGGACGCAAATGGACCAAACAAGAGGACAAAGGCAGGATAAC CAAACGACAAGAAGAAGAAACCACCGAGGCCACGCGGACAAGAGAAAGAGCAAAAGAAAGACCA CGACGGACGCAAAACAAGACGAGAGCCCCAACAAAACCAGGCACAAACAAAAAGAGCAAGAAAA AGAAAACCCCCGCAGGCAAGAAGAAAAAACAGGAACAGGAACGAGCAGGGCCCGGCCAACGAAG AAACAAACGCGACAACCCAAAGAGAACAAAGCGGCGGAGCCAAAAAACGCCAACACCACGGACA AACCAGGAAAAGCGAAAAAAACAAGCGCGAAAAAGAACAAACACAAAAAAGGAAACCCAGCAAC ACAAAGAAAACAACGCGAACAAGCCCAAAAGAAACACAAAGAACAGAAAAGCCAGGGAAAACGG ACAAAAAGGAACACAACAGGGCAAAAGGACAAGCAACGGACCGGCACGCACCCCAAGAAGCCGG AACACGCAAAGAAGAAGGACCAAAACACCAGAGACAAGAGACGGGCGCAAGAGAGGACAACCAA AGGACCCACAACAAAAAGGCAACAAAACACCAAGAGAAAAAAAGAAAGCCACCAACACCAGCCC CGAGCAAGTGACAAAAGGCAAGCGAAAAAGAAAGGGTGCAGAGACACAAAAGGACACCAGCGAA TCACCCAAGGAAAGAGGACGGAACCGGATAGGCGGCCGACAACCAAACAAGAGAAGTGGCAAAC GACAACAAGAAAACGCGAAATGCGGAACCGAAGGGCCCAGGACGAAGGTACAAAAGAAAGACAA CACAACAACAGATCGCAAGGGCAGGCAGGGACGACAGCGCTCGCACCCCCGAGGAGACAAGACC GACGTGAAAACCACGCCAGGGACACAAGCCCATCACCAACACGCCCAAAAAAGGCCAACCTACA ACCCACCCAAGAAGGCACCAAAAGTGGACGAAGGCAAAAACACACCCCGGAATACAAAGGACAG CCGAAAGAAGGGGACATGCCAAAACCAAAAGACGGAAAGAAGGGTCGGAAACGCGACAGGCAAA AGAAAGCCTACGGAACCGAAAACAACACGGAGGAAATCGCACAACAAAACAGACGCCACAAGGC TACACGCGGAAGAAAGACCGCGAAAACATGCGAAAACAAAGACCGCACGGAAAAAATCGGAAAG AACGAAAGACAACGCGAAGCTCCACAGGCACACAGAAAAGCGGACCAGAAAACCCACAACGAAA CCAAAGCCAAAAAAGGACCCCCCGGGGGCAACAAGGGGAGAACCACAAGACACACACGCGCAAA CCAGCGGCCGGCAGAAGAAAGGGCAGAGACGCGCAGAACAACAAAACCGGCAACAGGCAGACCG AAGAAACGCGCAAACGAACGAACGAAAAAAGAAACAAGACCCGGCAGGGGCACCAGGCAAAGAC GCGAAGCGGAAGGCCGCACCGACCCAGGCCCACGCGAAGGCAGGAAGAGAACGAAAGCCGACGCCAAACAAAAACAAAGGCGACAAGAGCGCCACAAGAGAAACGACAAAGACCGGAAGGAGAAGAAG CCGGCCGCGCCCGACCAAAAAACAAACGAAAAAAGAGCGCACAGACGGCACAAAAGCCGGAAAC AGCGCGGAACCCAAAACAGAAAAGAAAAAACGCGACAAAAGAAAGACGCACAAAAACGACCCGC AGCAACACGGACCCGAAAAACCAGACGACAAAAGAAAACGAGAAAAAAGGAAGGCGGCCCACCA GAACCCCAGCGGCAAGGCCAAGAAACGCACAGTAGAAGAGCCAAAACGCCAAAAGCCAAATTCA CTATGCCACAAAAGAACCGGAAAACAACGCCTCAGCACACACAACAGGAACAACGCCAATGAAC GAAAGGGAACGAAACAAAGCGGATAAAACAACAAAGGCGCCGAACGAAAACTAAAAAGGACCCA GGCGCGAGCAAGGCGTGGCAAAAGGCGCAAAAACAAAAAAGGGTCGCCCAAAAAAGAACAACAG ACGCAAATCCAAGACCACCGAGAGCAGAACGACCGTGGAACGAGAGCCGCAAGCGAGGACCAAT AACACAACCCAAGCAACCCAAGCGGCGTAACAGGCGCACAAGAAACACACGAGCATAAAAAACG AC C GAAAAG C C AAAC C GAG T AAAC AC AC AAGAAAC AAAAC C AAAAC G T AG C AC C AGAAAC C C AG AGGAAACCAGATAAGAAAAAGAGCCAACGCGGAGAAGCGTACCAAACCCAAAGAAGGACCAAAA AAGTAAAAACCACGGCAAACAGCAGGACGACTAGCGCAGGACCCCACAAACCAAAAGAGTAGGG CCCAAAAACGAGGACGCGGCACGTCAAACCAAAAGAACGACAACAAACAAATGGACAGAAAACG AGCGAAGCACGCGGGTAACAACAACCCAAAGAAGCGAAGGAAATACAAAGCAAAGAAGGAAAGA AC AC AAC AGAGAC AG C G C AG C AC G GAAAAAAGAC C AAAC C AGAC AAGAC C C AAAC AC C AC GAAA ACACAAAGGAGGCAGGAAGGACAAGACCAAGCCAGGAAAAGGGGGGAAGCCACGGAAGGAAGCC CGAACGGAAGCAAGCGAACGAAAAAAACCAGCAGGGGCAAACGAAAAGGGACGAGCCAGGAAAG GAAACCACGGGAGAACAAAACAAGACACCAGGCAAGGGCAAAAAGAGAAACCAAAACCGCCAAC GGAACCGCCCGGACACCACGCAACCAACCGACACGCGAGACGAAGCGGCCGAGCGGCAAAAGCG AGCGAGAAGAGAGGGAAGAACGAAAACAGACGACACGCCGAACAAGGCCCCACGGCGAACAGCC AACGCGAGCAACAAGAGCAAAGAGAGGGGAGGACGAACGAACAAAAGCCAAAAGAAAGAAGGAG GCGCGACAGGGCCAACCGAGCCGGAGACGAGCAGGGAGAGCACGACACAGCCGGACACGAGGCG GGCAAACCAAGAAAAAGAAAAACCAAGAACGAAAAACAACCCCAGAAGGCAAAAGTGCAACAGA CAAGAACCGCCAGGCAACCTGCCGCCGCCAGCCAAGGAAACCAACAATAAACACAGCAGGACCA AAAGACAGACGTCAAGAGGCCAAAAGCCCAAAAGGGCAATGGACCAAAAAAACAAAAACCCCAA ACGTACAACAACCGGAAAAAGAACAACAACGTGGCACAACACGGGCCGAAAAACCAAACTGAGG GAGGACACCACGAAACCCAGAAATAAGAAAAAAGCCCGAAACGCAGAAAACTAGCAAGCGCAAA GAAGGAACAAAGAAGTGGACACAAAACAAAGCCCAAAAAACGATCGAAGGCAACAAAAGAACAA AACCGAATGCAAAAGGCGAAGAAAGCGAAACAGAATGGAAAGCGCAAGAAACCAAGCAAAAAATCAACAGCACCACACAGACGAGACAAAATCCAAACCGGCGACAACGGAGAGCAACATCGGAGCCA AGAAAGGACAAAACCAGAATGCACAAACCACACAAAGCCAAAAGAGCTGGCGAGCCGAAACAAA AAGCAGCCGGGTGAACCACAAGAGAAGAAAAAAACAAAATAACGCACAACGGAGACGCCAAAGC AACTCCAAAGACAGAAAAAGGCCGGGCAACAAAAAGCAACAAGAAAAAGCAAAGCCAAGGCAGA AGGAAGCACCCAAGCGAGAGGCGAGACGGGAAACAGCACGGCCCCAAACGCAGACAAACCAAAAAGAAGCCAAAACAAAAGAAAGCCAGGAAAGGACACCCACGAAAACCACAGGAACCAAACCCAAA GGAACGGAAACGAGAACACGGAGCGACCAGCAGGCGGGGAAGGCCGAACCCCGGAAGCGCGCAA GAAAACACAACCGCAGAAACAGCAGAAACCGCGACAGCGGAAGCCAGCGCAACCAAGCCAGGGA AAAAGCAAAACAAGGAAAAAAGCCGGCGAAACAAGCGGCAACAACGCGAAAAAGGGGAAGGAGA AGGAGACAAACGAAACAACACAAGACCACGAGAGCCAAGAAAAAAACAACAAGGCGGGGAACGA ACCGGGGGGAAGGACAAGAACCAGCCCAACAAACCCACACGCACCCCAGAGAGAAAGCGCACAA GGCAAGACGACACAAACAACCACACAACCAAACGGAACGCACAGCAGAGAAAGGGACAAACAAC GGCCGGAGAGAAAGATAAAGCAAACAAAGGGGCCAAGAACGACTGGAACCGAGAGCGAGGGAAG AAAAAACTGCCACGCGGAGCAGAGGCAGAAACCAATAAAGAAAGGGCCAGAAAAGAAAGAAAGT GAAC AG C AAGAC AAG C AC AGAG GAG CAT C AGAGAC AAAAC C AC G C AAAC AAAAAG T GAC AC C C A CAACACAAGCCCGGAAGCGTAAGAGAAAAGGGAAGCAAACCACACGATAGGACAGAAAGAAACG GAGACACAAACTCAGAACAACGGGAGACGAGCCCGGCAATAGGAGAAGAGGAGGCGGGGGAAAA AAATAGACAAAGGAAGAGGGACGGAGGCAAATCAACCAAGCCCAAACAGAGCCGCAGGATGACA AGGGGCGCGCACCGACGGAGCAATAAAAGAGGACGACAAAAGGAGCAAAGATACACAGAAAAGC AAGCCAAGAGAAGAATGGACACACCACAACCGCCCGGCAGGAATGAGAAAGACAAACAACCAAG AAGGGGATAACAGCACGGCGACCCGACCACCCAGCTAAAAGAAAAAACAAGACCACACACAAGT GACAGAGGAACAAACAACCGGCCCAGCTAGAGGAGGCGACCAGGAAAAGAACACAGAAGAAAAA ACCAACCGAAGCCAACAACACCCAAAACAGCGGAACAAAGAACAACCAACGCGGCCGGAACGAA CACAAAAAGCGAGCCGAAAACAGACGAAACACGGAACACACGGACACCAACAGCACAGGAAACG CAGCGGGCGCCAAGACAGACGACCACAAACACAAAAGAGCGGCGAAGCCGGAGGAAAAAGGCAC ACAAACAAGAAGCGAAACGAAGAGACAGAAACAGAGCGGACGGCAGGCAAAACGGGACGACCAC AAAAGAGGGACCGAAGAAAAGCCAAACCACCCAGAACCCAGGCCCAAACACACGGAACAGGGGA ACACCACGCGCCGGAAGCACCAGCAGGCAACAGACAAAAGGCAGCGCAAAGGCAACGAGCACCA ACCAGGGCGAGGCCAGAAAAGACGAAACAAGCGAGGCGGCACGCAAACCACGAGGCGCACAGCA CAGGAACGAGACAAACCCACAGGCAAAACGCGCGAGGAACAAACAGGAGAACAAACCCCGAGCG GAC C AAAAAAAC GAGAAC C AAAAAGAG G G C GAC AAC AC C T GAAG C C AAAGAAAAGAC AAGAAC C CCATCCACGCGCACGGGACGAGCAGCAGGCGTCGAAAAAACGGGGCCAAGGGCAAGCGATGCCG AAAAAGCAACAGAAAGGAGAACATCCAGCAAGCAAGGGCAAGCAGGCGGGATGACCGAAAAAAG C AGAC AAAGAC AC CAT C AC GAAGAAC GAAAGAAAC GAG C AAAAT AGAGAAC G G C AC C AAC AC G G AACCCCATCCAAAACGGAACCGCACCGGGGCCACGTCCCCCCAACAGCGGCAAAGGAGAAAAAT AGACGAGCGCAGCACCGACCAGCCGGATAAGAGAAAGAAAGGCGAACGGGGCCACTGACGAAAG CGCCGGGCGACAACCACCATACAAACCAGAGAGCAGAAAGAGAAGGATGCGAACCAGGACAGCG AGCGACAAAAGTCAAGAGACGGCAAAAAAGAACACACAGTAGGACACAAAGACCGGCCAAACAC AAGTAGCGAAAAAGCGAGACAGGGACACCAGTCAGGACCCGGGACAGAGGCACGCGACGTCGAC GAGAGGGCAACGCAGGACAACCCTAACCGACGCGCGAAGCCAAAGACGCCATAGGCGAGAAAAACCACAACAGAAGGAAGGAAGCCACACGGCGGGAGGCGGAACCGCAGCGGAGGAAAAGGGCACGA GAGCGCACCGGCACACCACCAGGAGCCCAAAGCCGCGGAACAAGGCAACAAAAGGCAGAGGGCA AAAAAGCCACAAAACAGCCAAAAAACGGCGCAACACGCCGACCAGCACACGAAAAGCAGAGAAG C C C AGAAAAGAGAAAAAAC C GAG C GAAAAAAC AC C AAAC C AAAAC AG C GAAC C AAG C G C C C C AA CCGGAACAAAAAGGGCAAAGCGGAGCCGGCAGAACAAAGAAAGCAACAGAAGAACGAAGAAAGC GCACGGGGAACGGAACGAGGAGCACGAAAAGAAAGAAGAGAAAAGGCGCAAGGGCAGAACAGAC GCAAACAGGAAGGGAACCAAGAACCGACAAACGAGAGCCAAGCGGAAGAAAAAACGCACGACAA AGGAAAAAGACCAGAAAACCCAAACAAGCCGGCCGCCCACACAAACCCAACAGACACGACAGGA ACGGCCAACAAAAGGGAGGAAGGAGCGAGCAAGAAAACAAACCAGCAAAACGAGCACGAAGCGT AAGAGGCGGGAGAAAACGCAAAGCAACTACCCCAAGAACACACCAGGGAAACGACTCGAACGAA ACGACGCGAAAGAAAGCAGTGCCCAAACACCCCAGACACGGGGCCCATAAAACCAACGGACACA CGAGAGGAGGATCAAAGCAGGAAACCAAGGAGAGGCAACTGAACGAAAGCAAGCAAACAAAAAC GCGTACCCGGAAAAGAGAAAGGAACCAACAGTGAAACGAGAAGGGCAGGACCCAACGGATGAAC GAACAACGAAAGAACGCAAACCGTAGAGGGCACAGGCGAGAGCCACGAGGATCGACACAAGCAA CAAAGCAACACGCACTAGACACGCAGACAAAAGGGACAAAACGTACAACAAAGGAGGAAAAAGC C AAAC C G T AGAC C AGAGAGAAAC C C C AAC C C C GAC T C AC C GAC AC AAAC C AAAGAC C C AAAG C T AAGCGGAGCGCAAAGAAACGCGAGACATGACCGAAACAAAAGCAAAAGGACAAAGTAAGACAAA GCACACAAGCAAACAAAAGTAACGAAACCAAGACACAACACCACCAATAGCCAGAGGAGGCCCC GGAAGGCAGACTCGCAGGAAAAGAGCGAAAAACAAGGGCACAAAGCCAGAAACCCACCGGGAAA AGGCCCACCGGAGCGGAACAACCACGCGAGAGAACCAACGAAACCAGACACGCGACAAGAAAAC AACCGAACGCCGCAAAAAAAGAGCCGAAAGCAGGCACGAACCCCGCGACACCCAGGAAAAAGCA AGGGCCCGGCAAACAGAGACGAGAAAAACGCCCGAACACGAGCGAGAACGCGGGGACCCACGAA GAAAACAAGAGCACAGAAGGCGACACGGCCAGCAACAGAGCGAACAACGAACCAAAAACCAGAC AACGGAAAAGGAAGAAAGCAACAGGAAAAGGAAACAGAGAGGAAGCACAGCGACACGAACAGAA CCGAAAAGGCGACCCAAAACCGAAAAGCAAGAAAACGGGGCAAGGGGAACAAAAAGAACGCCAA CCAAGGCAAGCGGGCGACCGCAAAAAAGGGGCCAAACAGCAACCGCGAGACAACCAAGAAGAGA AAGAGACGGGCGGGAAACCCGCGAAACCGCCACGGCGAAGCGCAAACCAAAGAAGGAGACGACA AGAAGAACCGACAGGGGCGCAAGTAGAAGAGCACCCCAAAGGCGAACCCGATTCTTACTGCCAC ACACGAAACGAAAAAAGCGACCTCAGCCACACCAGGGAACGGGCGAAAGATACCCGACAAAGGC ACGAAAGAGACAAATGAGGGGACAGAAAGGCGGCAGCAAGGGTCAAGGGCAACGGGCCAGAAAG CGAAGGTCGCGCGACAAGAAGCGCACGGGAAACGTGCCACCACCAAAGGGAAAAAAGAGCAATA AAGAAACCAAGAGAAGCGGGCGCCAATAGAAAAGCCAAGACGAGACACGCCAACTACAACGAGA AGAAAACAGGCAGGAAAATCAAGCCACGAGAACGCAGAAAAAACCATGAGGAAAGGAAAAGAAA AAACGGGGAATAAAAGAACCAGAAAGGAGACACAGGGATCCAAAACCCGGGAGGACAAGCACCA AAT AAC AC C AC C AC AAAG GAAAC AGAAAC AT AG C AC C C AAAAGAC G C AAG C AC AGAAG T AGAC AACAAGCCCAAACACCGACCCCATAAACAGGCCAGCCACCACCAAACAAAATAAGAAGGAAACAA AACAGCAAAGCGCATACGCCACAGACCCAAACGGAGGAAAGATGGAAACAAAAACAGAGGACAG CGGAAATCACAAAACCACCAGACCCGGCCGAGACTCCAAAGACAAACAGGAAAAGGGGGAAAGG GAGCGACAAGGACAACGAAAAGAACAGGAAAAGCAAGAAGAAGGAACGGGACAGAAAGAGAAAA GCCCACGAACAACAGACGCGGGAGGAAGCACGAAGGCAGGAACACCCGCGCCAGGAGAAAAACA AGACCGAAAAAGACCCCACAACAAAAGCGGAAGGAACAGCGCAGCCCGCACGACCAAGGCAAGA ACAGCAAAACCGGGGGCACAAAAACACCGACACCCCGACGCAACAGGAGAGCCAGAACGAAAGA AAAGAAAGGAAACGACGGACCGAAAACCAAGGACAAACAACCGACCGAGGAAAGCACCCAACAG GAAACACGAGAGAACGGGACGAGCAGAACCGGGCACGCGGCAAGAGAGAAAAAGAAAAAGCGAC GCGAAAACCAAAGAGAGACGCCAGCGCAGGCGAGCGAAAAAAACCGACACGAGAAAAAGAAAAG CAGGCAGCACGCCCGAAAAAGGAAGGGCAGCAGCGAGAGCGACCACCGCGAAAAAACGCACGAA GAGAGAACGAGAGGCGAACCGCCAAAAAGCGGAAAGGGAACGAAAATAGAAAGACAACACAAGG GGGGGAGCGATAACGAAACCGCCCCAGGCAACGACCGATGAAAGAAAAACAGCAAAAGCGGAAA AGTGACCGAGGGCCCGAGAACAAGCCCAACTGAACGACCAAAGCAACGAGGAAGGGCCTACACA CGAGCCGACGAAACACGCCAACTGAAAACGCAGGAGCGACCACCGAGCAATAACAAACCGAACC AGAGAGGCGGAACATCCAGCAGAAAAGACACGGACACGAAGATCAGCAAAAAAAGGAAGAGGGG AGCGAATCCGACAGGGGACAACAGCCCGGCGCCATAGAAACAGGAAACCGCCAAGAAGCACATA AACCAAGACCCCACACCCCGCAAAGATAGAGCGGGGAAACAGCGACAAACAACATGGCGAAAAC AAGAAACAACGACAAAAATACGAAACGAAAGGAGAACAAGAAAAAATGAAGGGAAAAAGGCCAA CCCGCGCCAATCCGCCGGAACAGCAGCCAGCACCGAAGTAACAGGACACGAGAACAAAGGCGAA G G T AAAC GAG AAC GAG GAG AC G AGAAAAC AT AAC AGAAAC GAG C C GAAC AC GAG GAG G T AAAG G C AC GAAAAAAC AC AGAC AGAAAAAG C C C AC AAC C G G GAC AAAC AAC GAG C AGAAC AC AC GAAAA ACGAAAAAACGGGCAAAACGAAGCAGGGAACCGCAAAGACACAGGAGAAAAACGACACGAACAG AGCCGAGGGCCGACGCGGGAACAAGAACAACGCACGAAGGGGACAACCGGACCAGCAAGGAGAG AGCGGCCAACAGACACAAAGACCGAAAGAGGAAGAAACGCACGCAAAGCACGGAACGAGCACCA GCACCAGAAGAACCAGGCAAAAGAAGCAAAACGACGAAAAGCAAAAAGGAACAACGAACAGGAA GAAGGCAAGGCAGGAAAAAAGGAAAGACCAAACAGAACGCACACCCAGAAAAGAGGGGGAGAAC AGCACCCGCAAACAAACAAACAGGGCGAAAGAACAAGCCCAGAAGAGAAAAGACAACCAAAGAA GAAAAAGAAACAAGCCAAAACCAAACGAGAAAGAACGACAAGACGGGCAAAAACGCACAAGACG CGGCAAAGGCACGAGGGAAAAAGAGACACAGAAGGAAGCACACCAACCAAGCAGCGCAAGACCA CAAAAGTGCGACGGGGCGGAACAACACGGCAAGATAAACGGGCACAGACGGAACGAAAACGCTA AACGCCAACACGCAGCCCAAAGGACATCGAGCAGAGAACACAGAAAAAAAGGCATAAAAACGCC ACCAACAGCCAGAAGGCCTAGAAAAGCACAGACAGAAGCGGACAGCTAGGAGAACCCAGGCACG AAAACCAGGGTCGAGAGGAAAGGGGGGCGAAGAGAGGGTAAAGGAGAACCAGGACCAACCCAAA AATCCCAGCCGACAACGAGCAACAGAGAGCTACCCGAACGCCGGCAAACGACCAAAAGTACCAAGCACACACAACAAAAACACAGATCCAAGAAGAACAAAACAGCCGGAAGAATCGAAAAAGCCGCC CGCAGCCCACGAGGTACAACACGACAAACCAAGCAAGCGAACTAGACAGGGAACACAAAAACAA AGAGAGTCACCGCGAAAACAACGCAACAAAGGGATGGGACGAAACCCGGACAGAGACGAGCCTA AAAACAACGGGGGCGAACACGAACAATGCCCCACGAGAACAGCACACAAGGCAATGCAGGAAGC ACAAAAAAGAACCCCCAATACACCAAGAGAGACAAAGCGGAGCCACAGCCGCGGCGAGCCGGCA AAGCACCGACAAAGAACACCAACACCACGAAGAACCAAGGCACACCAGGAAAACGAGAAAGCACAGCAGGGCGGAACGAACCGAAAGGCAAACGAGGAAACAACAAAGCGGACACGCAAAACCCCAAC GCACCCGGAGAACGGAAACAAGCCCCACCAGAAACAAAGCGACAAGAGCCAGGCAAACAAGAAG AAAGAAGAAAAGGAGGGCGCGACAACACCCGGGAAAGAAAAACGGGGCAAAGGGAACAAACAAA CAAGCGGGCAGAGCGCGCAACAAACAGAAAGAGGGGCCAAAAAAGCAGCAGAGAACAGGAAAGC GCCCACCCCAGAAAAAACGAAGAAACAAAAACAAAGAGCGCACCACGAACGGCCCAAAAGAAGA AACGACACCCACGCAAGCCAAAAACCCACCCAGCAGCCGCGGGGAAACGAACAAAACGAGGGGCAACGCACAGGCAACGAAAACCACACCGCACCAGACAAGGAGCGGCAACCCGAGAAGCCACGAGA GAGAAGGGCACAGGAAGGGCAGGGAAACGATAGGGCACACAGAAAGCAAGAACAAAACTGAAGG GACGACAAGGCAGAACCAAACGTACCCAACCGCAGAAAAAAACGCCGCCGTAAGCAGAGAAGGC GCACGACAAAGGCATAACAAGGAACGGCAGAGCCGGACAGAATCGCGACACGGAAACGAGCGCG AAGGGATCAACACGGCGCCAGACAAACGGGAAAGTAACGAAAAGGAAAGAACAGCAACACCATG CCCAAGCCCACGCCCGCGCAGACAAGTCAAAAAGAGAGGAGCAGAGCACCGAAATAAAGGCCACCCCCACCCACAAAGGGCATACAAACCGAACAAACAAAAAGAGGCCATGCGAGAAACAAAACGAG AGAAAGAGAATCAAAGGAACAGAAAGGCCAGCAAAAGATCGGAAACACCCACAGAGACGCGAAA AATCGCCACAAACCAGGGAAGAAACAGCCGTACCAGACAAAGCAAACACAAAAAACCATGAAAC GAAAGGCCAACCCGAAAACACATAAAAAGAGACAGAACGAGGGGGAAGAATGGCCAGCAGGGAC GAAAGGAACGAAACTAGAAACGGAGCGACGAGCACACGCCAATAGACCAACCGCACAGCAAGAG CAAAGAAACGAGAGCGCAGGGGGCCGGCCGGCAACCCGACAGCACCCAAGAGAGAGAACCACAGAAGAAACAAAACGGAAGCGAGCACCCACCGACAAAGAAAACAGAGCGGGGCCCACAACGCCAGA CCACAGCCAACCGGCAGCAACGGAAGCCACCGGACACGAAGGACCAAGCAACAAGGAGACAAGC CCAAAACGCAACCAACCGCCGCAAAACAGGAAGGAAAACGGCCCAAAGCAAAAACAAAGAAAAA GACGGAACGAGCGCGCAAAAGCACCACAAGCAGGCCAGACGAAAAACAAAACGGGACAAAGAAA GGCACCAACCGCAGACACCAAGACACACGAAGGCCAAGAAGAACCGAGCGCACACAACAGGAAA AAACAGGACCGAAAAACCAGAGACGAGCAAAACGGACAGAGAACAGCGAGCGGGCGGGACAGCG GAG C GAG C C GAGAAGAGAC AC C GAG GAG GAAAAAAG GAAAC AC AAC C C AGAGAAAAAAC AAAAGAGCGAAACCAAGGCAAGAGGCCAACCGGAAAACGGAAGGAAGAAAAAAACGAGCTGACCCGGCG AAACCCACGAGAGAACACTACGCAGACAACAGACGAAGGGAGCCAGTAGACGAACAGGGGGCAG GAACAAAAGCTAAACAAGCAGACGCGAAAGACAAGAACTAAAAGGAACCCAGCCGGAAAAGGGA AG T C AAGAAAAAGAAAAAC AGAAAAAAGAAT GAG C C C AGAC AAAGAC C GAC C C G G C AG T AGAAGAACCAACGAGAGCACCAACACCTACAGAAAGAAACGCACGAAACACGGGCTGCGAAACGGACGA CAAACAAAAAAGGATAGACCAGCCCCGCGCAACCAGAGCGGATACGGCCCAAAAGGAGAAACCG CGAGGGTAAGCAACGAAGCGCACGAGAAGGACACTGAAGCCCCCCCGAAAACCAACCACCACTG ACCACGAAAAAAAGCAAAGCCGACCCTAGAAAACAACGCAGACGACAGCGGAGATGGGACCACG CCAAGAACACACAGACAATCGAAAAAAACAAGGCAAGAGGAGAAGATGACAAAAACAGAAAAGA GGCACGCAACTAAGAACAGACAAAAGAACGACGACAACTGAGAAAACCGCCAGCGAAGGAACAG GCTCCACCAAGAGAAAACAGAGGGACGAACGGGCAGCGAAACAAGAAGCCGCCGGACAGACACA GACCCCAGAAAAGCGGAAAAGAAGCAAGGGACGAACAACACAGGAACAGAAAAGCAGGCGGGCC C G GAG C GAG GAG C G C C GAAGAAAC AAC AAAAC C AAAAG C GAAAAAAC C AAAAAC GAAAGAC C AA ACCAAGAAGGGCCCCAGCCCGAAGGCAGCGCCAACAGGAGCAAAAAACAAAACGCAAAGAAGCC AGCACGCAACAGGGCAAACGCCGAAGCGGCGACGCCGCAAAAAAGACACGCCCGGACGAAGCAA CCGCAGAGGGAGAAACCAGAAAAGCAGAAACAAGCACCCCGACGAAAGAGAACGAGCGAGGAAA CAGAGCAAGAAGCCGACAAAGCAAAACAGGGCAGAGAAAGCAGGCCGAACCGAAAACGGACCCG GAAAAAAC C AGAC C AGAAAAGAAAAAAAC C AAAAAGAGAAAGAGAGAC AAAAAAC C G G C G G GAG CACCCAGGAACCGAAAACAGGAACAAAAACGAAAGACACACGAACAGAAACAGACAGCGGGGAA AAAAC AAG C G GAAAT AGAAGAG C C C AAAC C C AGAAG GAAAAAT T C

Claims

CLAIMSWHAT IS CLAIMED IS:

1. A polymer comprising a plurality of subunits, wherein:(a) a first subunit of the plurality of subunits comprises at least 10 convertible residues, wherein the at least 10 convertible residues are in a first state and are configured to transition irreversibly into a second state upon application of a stimulus;(b) a second subunit of said plurality of subunits does not comprise any convertible residues; and(c) each subunit of the plurality of subunits comprises at least 30 residues.

2. The polymer of claim 1, wherein said polymer comprises nucleic acid.

3. The polymer of claims 1 or 2, where said second subunit lacks one of: guanine (G), cytosine (C), thymine (T), or adenosine (A).

4. The polymer of any one of claims 1-3, wherein a convertible residue of said at least 10 convertible residues comprises a photo-modifiable group.

5. The polymer of claim 4, wherein said photo-modifiable group comprises a dye modification.

6. The polymer of any one of claims 1-5, wherein a convertible residue of said at least 10 convertible residues comprises a T.

7. The polymer of claim 6, wherein said dye modification is connected to said T with a first linker.

8. The polymer of claim 7, wherein said first linker comprises a 1,2, 3, -triazole ring, an ethylene, a methylene, an ether, an amide, a phosphodiester, or a thioether.

9. The polymer of any one of claims 1-8, wherein said first subunit comprises at least 60 nucleotides.

10. The polymer of any one of claims 1-9, wherein said first subunit comprises a GC content of 30-70%.

11. The method of any one of claims 1-10, wherein said stimulus comprises light.

12. The polymer of any one of claims 1-11, wherein said first subunit comprises a cleavable site.

13. The polymer of claim 12, wherein said cleavable site is a restriction site.

14. The polymer of claim 13, wherein said restriction site is cleavable by a golden gate assembly nuclease.

15. The polymer of any one of claims 1-14, wherein said second nucleic acid comprises at least 60 nucleotides.

16. The polymer of any one of claims 1-15, wherein said plurality of subunits comprises at least 50 subunits.

17. The polymer of any one of claims 1-15, wherein said plurality of said subunits comprises at least 50 copies of said first subunit.

18. The polymer of any one of claims 1-15, wherein said plurality of said subunits comprises at least 50 copies of said second subunit.

19. The polymer of any one of claims 1-18, wherein each copy of said first subunit is separated by at least one copy of said second subunit.

20. The polymer of any one of claims 1-18, wherein each copy of said second subunit is separated by at least one copy of said first subunit.

21. The polymer of any one of claims 1-20, wherein said polymer comprises at least 10k residues.

22. The polymer of claim 21, wherein said residues are nucleotides.

23. The polymer of any one of claims 1-22, wherein each subunit of said plurality of subunits is connected through a linker selected from the group consisting of 1,2,3,- triazole ring, an ethylene, a methylene, an ether, an amide, a phosphodiester, or a thioether.

24. A polymer comprising a plurality of subunits, wherein:(a) a first subunit of the plurality of subunits comprises at least 10 convertible residues, wherein the at least 10 convertible residues:(i) are in a first state;(ii) are spaced evenly within the first subunit; and(iii)are configured to transition into a second state upon application of a stimulus;(b) a second subunit of the plurality of subunits does not comprise any convertible residues; and(c) each subunit of the plurality of subunits comprises at least 30 residues.

25. The polymer of claim 24, wherein each convertible residue of said at least 10 convertible residues is separated by at least 1 non-convertible residue, wherein said at least 1 non-convertible residue does not change upon application of a stimulus.

26. The polymer of claim 25, wherein said at least 1 non-convertible residue comprises a nucleotide.

27. The polymer of and one of claims 24-26, wherein said polymer comprises nucleic acid.

28. The polymer of and one of claims 24-27, where said second subunit lacks one of: guanine (G), cytosine (C), thymine (T), or adenosine (A).

29. The polymer of and one of claims 24-28, wherein a convertible residue of said at least 10 convertible residues comprises a photo-modifiable group.

30. The polymer of claim 29, wherein said photo-modifiable group, comprises a dye modification.

31. The polymer of any one of claims 27-30, wherein a convertible residue of said at least 10 convertible residues comprises a T.

32. The polymer of claim 31, wherein said dye modification is connected to said T with a first linker.

33. The polymer of claim 32, wherein said first linker comprises a 1,2, 3, -triazole ring, an ethylene, a methylene, an ether, an amide, a phosphodiester, or a thioether.

34. The polymer of any one of claims 24-33, wherein said first subunit comprises at least 60 nucleotides.

35. The polymer of any one of claims 24-34, wherein said first subunit comprises a GC content of 30-70%.

36. The polymer of any one of claims 24-35, wherein said first subunit comprises a cleavable site.

37. The polymer of claim 36, wherein said cleavable site is a restriction site.

38. The polymer of claim 37, wherein said restriction site is cleavable by a golden gate assembly nuclease.

39. The polymer of any one of claims 24-38, wherein said second nucleic acid comprises at least 60 nucleotides.

40. The polymer of any one of claims 24-39, wherein said plurality of subunits comprises at least 50 subunits.

41. The polymer of any one of claims 24-39, wherein said plurality of said subunits comprises at least 50 copies of said first subunit.

42. The polymer of any one of claims 24-39, wherein said plurality of said subunits comprises at least 50 copies of said second subunit.

43. The polymer of any one of claims 24-42, wherein each copy of said first subunit is separated by at least one copy of said second subunit.

44. The polymer of any one of claims 24-42, wherein each copy of said second subunit is separated by at least one copy of said first subunit.

45. The polymer of any one of claims 24-44, wherein said polymer comprises at least 10k residues.

46. The polymer of claim 45, wherein said residues are nucleotides.

47. The polymer of any one of claims 24-46, wherein each subunit of said plurality of subunits is connected through a linker selected from the group consisting of 1,2,3,- triazole ring, an ethylene, a methylene, an ether, an amide, a phosphodiester, or a thioether.

48. A polymer comprising a plurality of subunits, wherein:(a) a first subunit of the plurality of subunits comprises at least 10 convertible residues, wherein each of the at least 10 convertible residues comprise a photo- modifiable group;(b) a second subunit of the plurality of subunits does not comprise any convertible residues; and(c) each subunit of the plurality of subunits comprises at least 30 residues.

49. The polymer of claim 48, wherein said photo-modifiable group comprises a dye modification.

50. The polymer of claim 49, wherein said dye modification comprises a Cy3 modification.

51. The polymer of claim 49, wherein said dye modification comprises a Cy5 modification.

52. The polymer of any one of claims 48-51, wherein said polymer comprises nucleic acid.

53. The polymer of any one of claims 48-51, where said second subunit lacks one of: guanine (G), cytosine (C), thymine (T), or adenosine (A).

54. The polymer of any one of claims 48-53 wherein a convertible residue of said at least 10 convertible residues comprises a photo-modifiable group.

55. The polymer of claim 54, wherein said photo-modifiable group, comprises a dye modification.

56. The polymer of any one of claims 48-55, wherein a convertible residue of said at least 10 convertible residues comprises a T.

57. The polymer of claim 56, wherein said dye modification is connected to said T with a first linker.

58. The polymer of claim 57, wherein said first linker comprises a 1,2, 3, -triazole ring, an ethylene, a methylene, an ether, an amide, a phosphodiester, or a thioether.

59. The polymer of any one of claims 48-58, wherein said first subunit comprises at least 60 nucleotides.

60. The polymer of any one of claims 48-59, wherein said first subunit comprises a GC content of 30-70%.

61. The polymer of any one of claims 48-60, wherein said stimulus comprises light.

62. The polymer of any one of claims 48-61, wherein said first subunit comprises a cleavable site.

63. The polymer of claim 62, wherein said cleavable site is a restriction site.

64. The polymer of claim 63, wherein said restriction site is cleavable by a golden gate assembly nuclease.

65. The polymer of any one of claims 48-64, wherein said second subunit comprises at least 60 nucleotides.

66. The polymer of any one of claims 48-65, wherein said plurality of subunits comprises at least 50 subunits.

67. The polymer of any one of claims 48-65, wherein said plurality of said subunits comprises at least 50 copies of said first subunit.

68. The polymer of any one of claims 48-65, wherein said plurality of said subunits comprises at least 50 copies of said second subunit.

69. The polymer of any one of claims 48-68, wherein each copy of said first subunit is separated by at least one copy of said second subunit.

70. The polymer of any one of claims 48-68, wherein each copy of said second subunit is separated by at least one copy of said first subunit.

71. The polymer of any one of claims 48-70, wherein said polymer comprises at least 10k residues.

72. The polymer of claim 71, wherein said residues are nucleotides.

73. The polymer of any one of claims 48-72, wherein each subunit of said plurality of subunits is connected through a linker selected from the group consisting of 1,2,3,- triazole ring, an ethylene, a methylene, an ether, an amide, a phosphodiester, or a thioether.

74. A method of processing a polymer, the method comprising:(a) providing a polymer comprising a plurality of subunits, wherein(i) a first subunit of the plurality of subunits comprises at least 10 convertible residues, wherein the at least 10 convertible residues are in a first state and transition irreversibly into a second state upon application of a stimulus;(ii) a second subunit of said plurality of subunits comprises non-convertible residues and does not comprise any convertible residues, wherein said non-convertible residues do not change upon application of a stimulus; and(iii)each subunit of said plurality of subunits comprises at least 30 residues; and(b) applying said stimulus to said first subunit of said plurality of subunits, thereby causing at least a portion of said at least 10 convertible residues to irreversibly transition into a second state.

75. The method of claim 74, wherein said at least 10 convertible residues are spaced evenly within the first subunit.

76. The method of claim 74 or 75, wherein each of said at least 10 convertible residues comprise a photo-modifiable group.

77. The method of claim 76, wherein said photo-modifiable group comprises a dye modification.

78. The method of any one of claims 74-77, wherein (b) comprises applying a light to the first subunit.

79. The method of any one of claims 74-78, wherein said polymer comprises a nucleic acid.

80. The method of any one of claim 74-79, wherein said second subunit lacks one of: guanine (G), cytosine (C), thymine (T), or adenosine (A).

81. The method of any one of claims 74-80, wherein a convertible residue of said at least10 convertible residues comprises a T.

82. The method of any one of claims 74-81, wherein said first subunit comprises at least 60 nucleotides.

83. The method of any one of claims 74-82, wherein said first subunit comprises a GC content of 30-70%.

84. The method of any one of claims 74-83, wherein said first subunit comprises a cleavable site.

85. The method of claim 84, wherein said cleavable site is a restriction site.

Images