Inducible gene expression system

Abstract

The present disclosure relates to the fields of molecular biology and nucleic acid technology. The present disclosure also relates to therapy and prophylaxis of disease.

Description

[0001]P37829 Inducible Gene Expression System This application claims priority from EP23178358.0 filed 9 June 2023, the contents and elements of which are herein incorporated by reference for all purposes. Technical Field The present disclosure relates to the fields of molecular biology and nucleic acid technology. The present disclosure also relates to therapy and prophylaxis of disease. Background Gene therapy as a modality aims at ameliorating disease-related phenotypes by using both viral and non- viral delivery systems. Significant efforts have been focusing on optimizing this therapy to be more efficient, non-immunogenic and less toxic while enabling a long-term expression of the gene of interest. One of the key challenges to achieve this goal is to regulate the expression of the transgene to meet the required level and to be expressed upon demand. For certain targets, where constitutive and unlimited expression leads to adverse events, regulated gene expression is necessary to render gene therapy a viable option as a treatment modality. One example is Rett Syndrome (RTT), an X-linked neurological disorder associated with severe motor abnormalities and reduced lifespan that occurs in 1 in 1,000 females. RTT is characterized by seemingly normal neurological and physical development during early postnatal period followed by a rapid regression with the loss of the purposeful motor skills and the onset of repetitive and autistic behaviors1,2. During the rapid progression stage, the child loses purposeful hand skills and spoken language, experiences motor impairments, and develops breathing abnormalities and may also develop autistic-like features and seizures. At later stages, further motor deterioration begins, typified by severe physical disability, which leads many patients to become dependent on the use of wheelchairs. Current treatment options are limited to symptom control. Mutations in the MECP2 gene on the X chromosome, encoding for methyl- CpG-binding protein 2 account for 95% of RTT cases3. MeCP2 is highly expressed in neurons and functions as a ubiquitous transcriptional regulator by binding to methylated DNA and recruiting protein partners and regulatory complexes to control transcriptional activity. MeCP2 regulates neuronal physiology and maintenance and landmark studies have demonstrated that restoring levels of the MeCP2 protein dramatically reverses symptoms in mice4,5. Given that it is a monogenetic disorder driven by the lack of MeCP2, a protein with multiple functions, gene therapy is one potential avenue to treat RTT. Studies in RTT mice have provided encouraging data showing attenuated neurological dysfunctions as well as extended lifespan by intravenous administration of an Adeno-associated virus serotype 9 (AAV9) expressing the wild-type (WT) MeCP2 gene5-8. Despite the promising potential of gene replacement therapy, high doses of MeCP2 by overexpression systems – which rely on the use of ubiquitous promoters resulting in uncontrolled level of the transgene – can lead to toxicity with phenotypes similar to those observed in duplication syndrome, a condition mainly affecting males, characterized by moderate to severe intellectual impairment, and caused by a duplication of the MeCP2 gene on the X-chromosome9,10. The requirement of keeping MeCP2 expression level within a window for normal function is one of the most challenging aspects that has yet to be solved. One solution P37829 would be to develop controlled transgene expression systems in order to overcome this limitation and make gene therapy a viable treatment option. Inducible gene expression systems allow for reversibility and flexibility and enable the production of therapeutics upon demand, thereby circumventing overdose-associated side effects. Such regulation can be achieved using small molecules, with which transgene expression can be induced (generating ON- switches) or repressed (OFF-switch). Among the existing inducible transcriptional gene regulatory systems, the tetracycline (Tet)-regulable system is the most widely exploited tool and can be used as an ON- or an OFF-switch. Tet-inducible systems, however, are derived from bacteria and require the expression of the regulator protein, e.g. the ON-switch components include the tetracycline-controlled transactivator (tTA), which consists of the bacterial tetR with a C-terminal domain of VP16 (virion protein 16), derived from the herpes simplex virus. The required co-expression of these components further increase the limitations in the size of the transgene for AAV packaging, and can cause both silencing and potential immunogenicity effects when introduced into human tissue, which has hampered further translation into the clinics11,12. Another class of genetic switches originating from bacteria are riboswitches, RNA elements that are able to control gene expression in response to ligand binding, have a small genomic footprint and do not depend on other proteins for activity, which renders these types of regulated gene expression an attractive alternative to protein-based expression control systems13. However, riboswitches suffer from a poor dynamic range as well as high basal activity14. A new class of small molecules that regulate splicing of SMN2 exon 7 was recently identified, via screening using a reporter system based on the SMN2 transcript (described e.g. in WO 2009 / 151546 A2). SMN2 reporter systems have since been proposed to be used as gene expression switches, where expression of a transgene is regulated through small molecule-controlled splicing of the expression cassette (Monteys et al. Nature (2021) 596: 291-295). Known human SMN2 exon 6 to exon 8-derived transgene expression systems are described e.g. in Zhang, et al., Gene Ther. (2001) 8: 1532-1538, WO 2022 / 204471 A1, Monteys et al. Nature (2021) 596: 291-295 and WO 2021 / 163556 A1. However, these known SMN2-based switch systems have very long nucleotide sequences, limiting the size of the transgene that can be employed under the control of the system. That is, the size of an insert comprising the switch and the coding sequence for a therapeutic polypeptide to be delivered as gene therapy would very often be much larger than the packaging limit for vectors routinely employed in the delivery of gene therapies, e.g. adeno-associated viral (AAV) vectors. Summary In a first aspect, the present disclosure provides a polynucleotide comprising in 5’ to 3’ order: (i) a first nucleotide sequence, comprising a nucleotide sequence having at least 80% sequence identity to a nucleotide sequence according to SEQ ID NO:222, wherein the first nucleotide sequence does not comprise SEQ ID NO:2; (ii) a second nucleotide sequence, comprising a nucleotide sequence having at least 80% sequence identity to SEQ ID NO:7 at its 5’ end, and comprising a nucleotide sequence having at least P37829 80% sequence identity to a nucleotide sequence according to SEQ ID NO:378 at its 3’ end, and consisting of fewer than 1044 nucleotides; (iii) a third nucleotide sequence consisting of a nucleotide sequence having at least 80% sequence identity to a nucleotide sequence according to SEQ ID NO:226; (iv) a fourth nucleotide sequence, comprising a nucleotide sequence having at least 80% sequence identity to a nucleotide sequence according to SEQ ID NO:15 at its 5’ end, and comprising a nucleotide sequence having at least 80% sequence identity to SEQ ID NO:16 at its 3’ end; (v) a fifth nucleotide sequence: (a) consisting of the dinucleotide ‘GA’, ‘TG’ or ‘TT’, or (b) comprising a nucleotide sequence having at least 80% sequence identity to a nucleotide sequence according to SEQ ID NO:19, wherein the nucleotide sequence comprises ‘GA’, ‘TG’ or ‘TT’ at the positions corresponding to positions 1 and 2 of SEQ ID NO:19, or (c) encoding a polypeptide of interest, and comprising ‘GA’, ‘TG’ or ‘TT’ at positions 1 and 2; and (vi) where the fifth nucleotide sequence is a nucleotide sequence according to (v)(a) or (v)(b), a sixth nucleotide sequence encoding a polypeptide of interest; wherein the polynucleotide comprises a start codon 5’ to the nucleotide sequence encoding a polypeptide of interest. In a second aspect, the present disclosure provides a polynucleotide comprising in 5’ to 3’ order: (i) a first nucleotide sequence, comprising a nucleotide sequence having at least 80% sequence identity to a nucleotide sequence according to SEQ ID NO:1, wherein the first nucleotide sequence does not comprise SEQ ID NO:2; (ii) a second nucleotide sequence, comprising a nucleotide sequence having at least 80% sequence identity to SEQ ID NO:7 at its 5’ end, and comprising a nucleotide sequence having at least 80% sequence identity to SEQ ID NO:8 at its 3’ end, and consisting of fewer than 1044 nucleotides; (iii) a third nucleotide sequence consisting of a nucleotide sequence having at least 80% sequence identity to a nucleotide sequence according to SEQ ID NO:26, wherein the third nucleotide sequence comprises ‘A’ at the position corresponding to position 2 of SEQ ID NO:12; (iv) a fourth nucleotide sequence, comprising a nucleotide sequence having at least 80% sequence identity to SEQ ID NO:15 at its 5’ end, and comprising a nucleotide sequence having at least 80% sequence identity to SEQ ID NO:16 at its 3’ end; (v) a fifth nucleotide sequence: (a) consisting of the trinucleotide ‘GAG’ or (b) encoding a polypeptide of interest, and comprising ‘GAG’ at positions 1 to 3; and (vi) where the fifth nucleotide sequence is a nucleotide sequence according to (v)(a), a sixth nucleotide sequence encoding a polypeptide of interest; wherein the polynucleotide comprises a start codon 5’ to the nucleotide sequence encoding a polypeptide of interest. In some embodiments in accordance with the various aspects of the present disclosure, when the polynucleotide is a polyribonucleotide, splicing of the polyribonucleotide in the absence of a splicing modifier that promotes SMN2 exon 7 inclusion yields polyribonucleotides substantially lacking the third nucleotide sequence. P37829 In some embodiments, the first nucleotide sequence comprises a nucleotide sequence according to SEQ ID NO:222. In some embodiments, the first nucleotide sequence comprises, or consists of, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:106, SEQ ID NO:219 or SEQ ID NO:220. In some embodiments, the first nucleotide sequence comprises, or consists of, SEQ ID NO:3. In some embodiments, the second nucleotide sequence comprises SEQ ID NO:7 at its 5’ end, and comprises SEQ ID NO:8 or SEQ ID NO:377 at its 3’ end. In some embodiments, the second nucleotide sequence consists of fewer than 500 nucleotides. In some embodiments, the second nucleotide sequence comprises, or consists of, SEQ ID NO:9, SEQ ID NO:10 or SEQ ID NO:228. In some embodiments, the first nucleotide sequence comprises, or consists of, SEQ ID NO:10. In some embodiments, the third nucleotide sequence consists of a nucleotide sequence according to SEQ ID NO:226. In some embodiments, the third nucleotide sequence consists of SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:223 or SEQ ID NO:224. In some embodiments, the third nucleotide sequence consists of a nucleotide sequence according to SEQ ID NO:26. In some embodiments, the third nucleotide sequence consists of SEQ ID NO:13 or SEQ ID NO:27. In some embodiments, the fourth nucleotide sequence comprises SEQ ID NO:15 or SEQ ID NO:379 at its 5’ end, and comprises SEQ ID NO:16 at its 3’ end. In some embodiments, the fourth nucleotide sequence consists of fewer than 500 nucleotides. In some embodiments, the fourth nucleotide sequence comprises, or consists of, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:227 or SEQ ID NO:340. In some embodiments, the fourth nucleotide sequence comprises, or consists of, SEQ ID NO:17. In some embodiments, the fifth nucleotide sequence: (a) consists of the dinucleotide ‘GA’ or ‘TG’, or (b) comprises, or consists of, a nucleotide sequence according to SEQ ID NO:19. In some embodiments, the fifth nucleotide sequence: (a) consists of the dinucleotide ‘GA’ or ‘TG’, or (b) comprises, or consists of, SEQ ID NO:20 or SEQ ID NO:21. In some embodiments, the polynucleotide comprises a nucleotide sequence having at least 80% sequence identity to a nucleotide sequence selected from the group consisting of SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:111, SEQ ID NO:114, SEQ ID NO:116, SEQ ID NO:164 and SEQ ID NO:171. In some embodiments, the polynucleotide comprises at least 80% sequence identity to SEQ ID NO:28 or SEQ ID NO:29. In some embodiments, the polynucleotide further comprises a promoter sequence 5’ to the start codon. In some embodiments, the polynucleotide further comprises a polyadenylation sequence 3’ to the nucleotide sequence encoding a polypeptide of interest. In some embodiments, the polynucleotide comprises an inverted terminal repeat (ITR) sequence at its 5’ end, and an ITR sequence at its 3’ end. P37829 The present disclosure also provides a vector comprising a polynucleotide according to the present disclosure. In some embodiments, the vector is an adeno-associated virus (AAV) vector. The present disclosure also provides a pharmaceutical composition comprising a polynucleotide or vector according to the present disclosure, and a pharmaceutically-acceptable carrier, diluent, excipient or adjuvant. The present disclosure also provides a cell comprising a polynucleotide or vector according to the present disclosure. In some embodiments, the cell further comprises a splicing modifier that promotes SMN2 exon 7 inclusion. In some embodiments, the splicing modifier that promotes SMN2 exon 7 inclusion is risdiplam. The present disclosure also provides a method for modifying a cell to express a polypeptide of interest, comprising: (i) introducing into a cell a polynucleotide or vector according to the present disclosure; and (ii) subsequently contacting the cell with a splicing modifier that promotes SMN2 exon 7 inclusion. In some embodiments, the splicing modifier that promotes SMN2 exon 7 inclusion is risdiplam. The present disclosure also provides a method for expressing a polypeptide of interest in a cell, comprising contacting a cell according to the present disclosure with a splicing modifier that promotes SMN2 exon 7 inclusion. In some embodiments, the splicing modifier that promotes SMN2 exon 7 inclusion is risdiplam. The present disclosure also provides a method for inhibiting expression of a polypeptide of interest in a cell, comprising contacting a cell according to the present disclosure with a splicing modifier that promotes SMN2 exon 7 inclusion. The present disclosure also provides a method for modifying a cell to express a polypeptide of interest, comprising introducing into a cell a polynucleotide or vector according to the present disclosure. The present disclosure also provides a polynucleotide, vector or pharmaceutical composition according to the present disclosure, for use in a method of medical treatment or prophylaxis. The present disclosure also provides a polynucleotide, vector or pharmaceutical composition according to the present disclosure, for use in treating or preventing a disease or condition that would derive therapeutic or prophylactic benefit from an increase in the level of expression of the polypeptide of interest. The present disclosure also provides the use of a polynucleotide, vector or pharmaceutical composition according to the present disclosure, in the manufacture of a medicament for treating or preventing a disease or condition that would derive therapeutic or prophylactic benefit from an increase in the level of expression of the polypeptide of interest. P37829 The present disclosure also provides a method of treating or preventing a disease or condition that would derive therapeutic or prophylactic benefit from an increase in the level of expression of the polypeptide of interest, comprising administering to a subject a polynucleotide, vector or pharmaceutical composition according to the present disclosure. In some embodiments, treating or preventing the disease or condition further comprises administering to the subject a splicing modifier that promotes SMN2 exon 7 inclusion. In some embodiments, the splicing modifier that promotes SMN2 exon 7 inclusion is risdiplam. In some embodiments, the disease or condition is a disease or condition characterised by deficiency of the polypeptide of interest. The present disclosure also provides a kit, comprising: (i) a polynucleotide, vector or pharmaceutical composition according to the present disclosure; and (ii) a splicing modifier that promotes SMN2 exon 7 inclusion. In some embodiments, the splicing modifier that promotes SMN2 exon 7 inclusion is risdiplam. Description The present disclosure relates to inducible transgene expression systems using small molecule splicing modifiers (SMSM), and based on the described mechanism of action of the Survival of Motor Neuron 2 (SMN2) splicing modifier risdiplam (and variants thereof). The SMSM binding sites for SMN2 have previously been described to be two distinct sites within SMN2 exon 7 pre-mRNA: the ESE2 region and the 5’ splice donor site (5’ss) (Figure 2a)15. Interaction of the small molecules with the mRNA-protein complex is thought to be critical for the high selectivity of the compound. This study suggested that both ESE2 and 5’ss regions are required for full activity of the SMSM compounds in a dose-dependent manner15. Structural analysis using a compound from the same chemical class as risdiplam (SMN-C5) has demonstrated that the drug selectively promotes the recognition of the weak 5’ splice site of SMN2 exon 7 by U1 snRNP by stabilizing an unpaired adenine at the exon-intron junction in the RNA helix16. The present disclosure provides novel SMN2 exon 6 to exon 8-derived constructs providing for the SMSM-inducible regulation of transgene expression, which are suitable to be employed for chemically- inducible regulation of the expression of gene therapies. In particular, the present disclosure provides ON-switch constructs: (i) having a size permitting their application for the SMSM-inducible expression of polypeptides to be delivered as gene therapies, (ii) minimising undesirable expression of the polypeptide in the absence of the SMSM, and (iii) which are highly responsive to the SMSM, thus providing for strong induction of expression of the polypeptide in the presence of the SMSM, and (iv) that minimise the number of / completely remove extraneous amino acids P37829 at the N-terminus of the expressed polypeptide. The present disclosure also provides OFF-switch constructs: (i) having a size permitting their application for the SMSM-inducible expression of polypeptides to be delivered as gene therapies, (ii) maximising expression of the polypeptide in the absence of the SMSM, and (iii) which are highly responsive to the SMSM, thus minimising expression of the polypeptide in the presence of the SMSM, and (iv) that minimise the number of / completely remove extraneous amino acids at the N-terminus of the expressed polypeptide. Polynucleotides Aspects and embodiments of the present disclosure relate to polynucleotides. A 'polynucleotide' refers to a polymer chain of a plurality of nucleotide monomers linked by bonds between the monomers, typically phosphodiester bonds (e.g. in the case of polynucleotides formed by naturally-occurring nucleotide monomers). Polynucleotides include oligonucleotides, which generally comprise ≤50 nucleotides. A polynucleotide may be single-stranded, or may be double-stranded (i.e. may comprise a duplex formed by hydrogen-bonding between complementary nucleotides). Polynucleotides according to the present disclosure may comprise or consist of: single-stranded DNA, double-stranded DNA, DNA that is a mixture of single- and double-stranded regions, single-stranded RNA, double- stranded RNA, RNA that is mixture of single- and double-stranded regions, single-stranded molecules comprising DNA and RNA, double-stranded molecules comprising DNA and RNA, and molecules comprising DNA and RNA having a mixture of single- and double-stranded regions. In some embodiments, a polynucleotide comprises or consists of DNA. In some embodiments, a polynucleotide is a polydeoxyribonucleotide. In some embodiments, a polynucleotide comprises or consists of RNA. In some embodiments, a polynucleotide is a polyribonucleotide. In aspects and embodiments wherein the polynucleotide of the present disclosure is defined by reference to a given nucleotide sequence, and wherein the given nucleotide sequence comprises or consists of RNA and / or is a polyribonucleotide, it will be appreciated that instances of ‘T’ for thymidine in such sequences are replaced with ‘U’, for uracil. The present disclosure also contemplates polynucleotides comprising modified nucleotides, e.g. in which the phosphonate and / or ribose and / or base of a deoxyribonucleotide or ribonucleotide is / are chemically modified. Nucleotide modifications contemplated in accordance with the present disclosure include those described in Hu et al., Sig. Transduc. Tar. Ther. (2020) 5(101), which is hereby incorporated by reference in its entirety. Phosphonate modifications may be selected from phosphorothioate (e.g. Rp isomer, Sp isomer), phosphorodithioate, methylphosphonate, methoxypropylphosphonate, 5'-(E)-vinylphosphonate, 5'- methylphosphonate, (S)-5'-C-methyl with phosphate, 5’-phosphorothioate, and peptide nucleic acid modifications. Ribose modifications may be selected from 2'-O-methyl, 2'-O-methoxyethyl, 2’-fluoro, 2’- deoxy-2’-fluoro, 2'-methoxyethyl, 2'-O-alkyl, 2'-O-allyl, 2'-C-allyl, 2'-deoxy, 2'-hydroxyl, 2'-arabino-fluoro, 2’-O-benzyl, 2’-O-methyl-4-pyridine, locked nucleic acid, (S)-cEt-BNA, tricyclo-DNA, PMO, unlocked P37829 nucleic acid, hexitol nucleic acid and glycol nucleic acid modifications. Base modifications may be selected from pseudouridine, 2'-thiouridine, N6'-methyladenosine, 5’-methylcytidine, 5’-fluoro-2’- deoxyuridine, N-ethylpiperidine 7'-EAA triazole-modified adenine, N-ethylpiperidine 6'-triazole-modified adenine, 6'-phenylpyrrolo-cytosine, 2',4'-difluorotoluyl ribonucleoside and 5'-nitroindole modifications. In some embodiments, a modified nucleotide may be selected from 2'-O-methyluridine-3'-phosphate, 2'- O-methyladenosine-3'-phosphate, 2'-O-methylguanosine-3'-phosphate, 2'-O-methylcytidine-3'-phosphate, 2'-O-methyluridine-3'-phosphorothioate, 2'-O-methyladenosine-3'-phosphorothioate, 2'-O- methylguanosine-3'-phosphorothioate, 2'-O-methylcytidine-3'-phosphorothioate, 2'-fluorouridine-3'- phosphate, 2'-fluoroadenosine-3'-phosphate, 2'-fluoroguanosine-3'-phosphate, 2'-fluorocytidine-3'- phosphate, 2'-fluorocytidine-3'-phosphorothioate, 2'-fluoroguanosine-3'-phosphorothioate, 2'- fluoroadenosine-3'-phosphorothioate, and 2'-fluorouridine-3'-phosphorothioate. Nucleotide sequences of the polynucleotides of the present disclosure Polynucleotides of the present disclosure are defined herein by reference to constituent nucleotide sequences. It will be appreciated that the constituent nucleotide sequences of polynucleotides according to the present disclosure are provided as subsequences of the complete sequence of the polynucleotide. In some aspects and embodiments, the constituent nucleotide sequences of polynucleotides according to the present disclosure are provided in a particular order in the sequence of the polynucleotide, e.g. from 5’ to 3’. By way of illustration, the first nucleotide sequence is provided 5’ to (i.e. upstream of) the second nucleotide sequence, in the context of the sequence of the polynucleotide. Similarly, the second nucleotide sequence is 5’ to the third nucleotide sequence, etc. The constituent nucleotide sequences of the polynucleotides of the present disclosure are non- overlapping. In some embodiments, constituent nucleotide sequences of the polynucleotides are provided in tandem in the context of the complete sequence of the polynucleotide. In some embodiments, constituent nucleotide sequences of the polynucleotide are immediately adjacent to one another (i.e. the 3’ nucleotide of a given nucleotide sequence is followed immediately by the 5’ nucleotide of another given nucleotide sequence, in the context of the complete sequence of the polynucleotide). By way of illustration, in the polynucleotide of SEQ ID NO:22, positions 1 to 45 form the first nucleotide sequence, positions 46 to 309 form the second nucleotide sequence, positions 310 to 364 form the third nucleotide sequence, positions 356 to 616 form the fourth nucleotide sequence, and positions 617 and 618 form the fifth nucleotide sequence. First nucleotide sequence The first nucleotide sequence according to the present disclosure comprises, or consists of, a nucleotide sequence which is a variant of human SMN2 exon 6. A ‘variant’ of a given reference nucleotide sequence comprises one or more differences relative to the reference nucleotide sequence. For example, a variant P37829 of a given reference nucleotide sequence may comprise insertion, deletion or substitution of one or more nucleotides relative to the reference nucleotide sequence. Accordingly, in some embodiments, the first nucleotide sequence does not consist of, or does not comprise, SEQ ID NO:2. In some embodiments, the first nucleotide sequence comprises, or consists of, a nucleotide sequence having <100% sequence identity to SEQ ID NO:2. In some embodiments, the first nucleotide sequence comprises, or consists of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to a nucleotide sequence according to SEQ ID NO:1. It will be appreciated that ‘a nucleotide sequence according to SEQ ID NO:1’ refers to a nucleotide sequence conforming to the consensus nucleotide sequence of SEQ ID NO:1. Exemplary sequences conforming to the consensus nucleotide sequence of SEQ ID NO:1 include SEQ ID NOs:3, 4, 5, 6 and 106. In some embodiments, the first nucleotide sequence comprises, or consists of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:3. In some embodiments, the first nucleotide sequence comprises, or consists of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to a nucleotide sequence according to SEQ ID NO:4. In some embodiments, the first nucleotide sequence comprises, or consists of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:5. In some embodiments, the first nucleotide sequence comprises, or consists of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:6. In some embodiments, the first nucleotide sequence comprises, or consists of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to a nucleotide sequence according to SEQ ID NO:221. Exemplary sequences conforming to the consensus nucleotide sequence of SEQ ID NO:1 include SEQ ID NOs:219 and 220. In some embodiments, the first nucleotide sequence comprises, or consists of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to a nucleotide sequence according to SEQ ID NO:222. In some embodiments, the first nucleotide sequence comprises ‘CAG’ at the positions corresponding to positions 109 to 111 of SEQ ID NO:2 (cf. e.g. positions 109 to 111 of SEQ ID NO:6). As explained herein, position(s) of a nucleotide sequence which ‘corresponds to’ specified position(s) of a reference nucleotide sequence can be identified by sequence alignment of the subject sequence to the reference sequence, e.g. using sequence alignment software such as ClustalOmega (Söding, J.2005, P37829 Bioinformatics 21, 951-960). By way of illustration, it will be appreciated that positions 43 to 45 of SEQ ID NO:3 correspond to positions 109 to 111 of SEQ ID NO:2. Similarly, positions 45 to 47 of SEQ ID NO:4 correspond to positions 109 to 111 of SEQ ID NO:2. In some embodiments, the first nucleotide sequence comprises ‘CTG’ at the positions corresponding to positions 109 to 111 of SEQ ID NO:2 (cf. e.g. positions 109 to 111 of SEQ ID NO:5). In some embodiments, the first nucleotide sequence comprises ‘GGC’ at the positions corresponding to positions 64 to 66 of SEQ ID NO:2 (cf. e.g. positions 64 to 66 of SEQ ID NO:5, positions 64 to 66 of SEQ ID NO:6). In some embodiments, the first nucleotide sequence comprises ‘GGC’ at the positions corresponding to positions 82 to 84 of SEQ ID NO:2 (cf. e.g. positions 16 to 18 of SEQ ID NO:3, positions 18 to 20 of SEQ ID NO:4, positions 82 to 84 of SEQ ID NO:5). In some embodiments, the first nucleotide sequence comprises ‘GGC’ at the positions corresponding to positions 64 to 66 of SEQ ID NO:2, and comprises ‘GGC’ at the positions corresponding to positions 82 to 84 of SEQ ID NO:2. In some embodiments, the first nucleotide sequence comprises ‘GTG’ at the positions corresponding to positions 109 to 111 of SEQ ID NO:2. In some embodiments, the first nucleotide sequence comprises ‘TTG’ at the positions corresponding to positions 109 to 111 of SEQ ID NO:2. In some embodiments, the first nucleotide sequence comprises ‘TAG’ at the positions corresponding to positions 109 to 111 of SEQ ID NO:2. In some embodiments, the first nucleotide sequence comprises ‘CAG’ at the positions corresponding to positions 39 to 41 of SEQ ID NO:2. In some embodiments, the first nucleotide sequence comprises ‘GGC’ at the positions corresponding to positions 82 to 84 of SEQ ID NO:2. In some embodiments, the first nucleotide sequence consists of fewer than 111 nucleotides. In some embodiments the first nucleotide sequence consists of <100 nucleotides, e.g. one of <85 nucleotides, <80 nucleotides, <75 nucleotides, <70 nucleotides, <65 nucleotides, <60 nucleotides, <55 nucleotides, <50 nucleotides or ≤45 nucleotides. In some embodiments, the first nucleotide sequence consists of 45 nucleotides. In some embodiments, the first nucleotide sequence consists of 51 nucleotides. In some embodiments, the first nucleotide sequence consists of 81 nucleotides. In some embodiments, the first nucleotide sequence comprises, or consists of: (i) a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to a nucleotide sequence according to SEQ ID NO:1; and (ii) comprises ‘GGC’ at the positions corresponding to positions 82 to 84 of SEQ ID NO:2; and (iii) consists of ≤45 nucleotides. Examples of such first nucleotide sequences include SEQ ID NOs:3, 4 and 106. P37829 In some embodiments, the first nucleotide sequence comprises, or consists of: (i) a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to a nucleotide sequence according to SEQ ID NO:1; and (ii) comprises ‘GGC’ at the positions corresponding to positions 64 to 66 of SEQ ID NO:2; and (iii) comprises ‘GGC’ at the positions corresponding to positions 82 to 84 of SEQ ID NO:2; and (iv) comprises ‘CTG’ at the positions corresponding to positions 109 to 111 of SEQ ID NO:2. An example of such a first nucleotide sequence is SEQ ID NO:5. In some embodiments, the first nucleotide sequence comprises, or consists of: (i) a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to a nucleotide sequence according to SEQ ID NO:1; and (ii) comprises ‘GGC’ at the positions corresponding to positions 64 to 66 of SEQ ID NO:2; and (iii) comprises ‘GGC’ at the positions corresponding to positions 82 to 84 of SEQ ID NO:2; and (iv) comprises ‘CAG’ at the positions corresponding to positions 109 to 111 of SEQ ID NO:2. An example of such a first nucleotide sequence is SEQ ID NO:6. In some embodiments, a polynucleotide according to the present disclosure comprises a nucleotide sequence (e.g. a first nucleotide sequence) comprising, or consisting of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to a nucleotide sequence selected from SEQ ID NOs:3, 5, 6, 219, 220, and 230 to 237. In some embodiments, a polynucleotide according to the present disclosure does not comprise the nucleotide sequence of SEQ ID NO:2. In some embodiments, a polynucleotide according to the present disclosure comprises a nucleotide sequence (e.g. a first nucleotide sequence) comprising, or consisting of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:3. In some embodiments, a polynucleotide according to the present disclosure comprises a nucleotide sequence (e.g. a first nucleotide sequence) comprising, or consisting of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:5. In some embodiments, a polynucleotide according to the present disclosure comprises a nucleotide sequence (e.g. a first nucleotide sequence) comprising, or consisting of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:6. In some embodiments, a polynucleotide according to the present disclosure comprises a nucleotide sequence (e.g. a first nucleotide sequence) comprising, or consisting of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:219. In some embodiments, a polynucleotide according to the present disclosure comprises a nucleotide sequence (e.g. a first nucleotide sequence) comprising, or consisting of, a nucleotide sequence having at least 80% (e.g. one P37829 of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:220. Second nucleotide sequence The second nucleotide sequence according to the present disclosure comprises, or consists of, a nucleotide sequence which is a variant of human SMN2 intron 6. Accordingly, in some embodiments, the second nucleotide sequence does not consist of, or does not comprise, SEQ ID NO:30. In some embodiments, the second nucleotide sequence comprises, or consists of, a nucleotide sequence having <100% sequence identity to SEQ ID NO:30. In some embodiments, the second nucleotide sequence comprises a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:7 at its 5’ end. In some embodiments, the second nucleotide sequence comprises a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to a nucleotide sequence according to SEQ ID NO:378 at its 3’ end. It will be appreciated that ‘a nucleotide sequence according to SEQ ID NO:378’ refers to a nucleotide sequence conforming to the consensus nucleotide sequence of SEQ ID NO:378. Exemplary sequences conforming to the consensus nucleotide sequence of SEQ ID NO:378 include SEQ ID NO:8 and SEQ ID NO:377. In some embodiments, the second nucleotide sequence comprises a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:8 at its 3’ end. In some embodiments, the second nucleotide sequence comprises a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:377 at its 3’ end. In some embodiments, the second nucleotide sequence comprises a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:7 at its 5’ end, and comprises a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:8 at its 3’ end. In some embodiments, the second nucleotide sequence comprises a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:7 at its 5’ end, and comprises a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:377 at its 3’ end. As used herein, the ‘5’ end’ of a given nucleotide sequence refers to the region of the nucleotide sequence formed by nucleotides 5’ to (i.e. upstream of, in the context of the complete sequence of the given nucleotide sequence) the midpoint of the given nucleotide sequence, or a subsequence of this region. P37829 In a nucleotide sequence having an even number of nucleotides, the region 5’ to the ‘midpoint’ includes the nucleotide immediately preceding the midpoint. For example, in a nucleotide sequence consisting of 10 nucleotides, the region 5’ to the midpoint consists of positions 1 to 5. Similarly, in a nucleotide sequence having an even number of nucleotides, the region 3’ to the ‘midpoint’ includes the nucleotide immediately after the midpoint. For example, in a nucleotide sequence consisting of 10 nucleotides, the region 3’ to the midpoint consists of positions 6 to 10. In a nucleotide sequence having an odd number of nucleotides, the region 5’ to the ‘midpoint’ includes the nucleotides 5’ to (i.e. upstream of) the nucleotide provided at the midpoint. For example, in a nucleotide sequence consisting of 9 nucleotides, the region 5’ to the midpoint consists of positions 1 to 4. Similarly, in a nucleotide sequence having an odd number of nucleotides, the region 3’ to the ‘midpoint’ includes the nucleotides 3’ to (i.e. downstream of) the nucleotide provided at the midpoint. For example, in a nucleotide sequence consisting of 9 nucleotides, the region 3’ to the midpoint consists of positions 6 to 9. By way of illustration, in SEQ ID NO:9, which consists of 414 nucleotides, a sequence provided at the 5’ end of SEQ ID NO:9 refers to a nucleotide sequence formed by positions 1 to 207 of SEQ ID NO:9, or a subsequence thereof. Conversely, the ‘3’ end’ of a given nucleotide sequence refers to the region of the nucleotide sequence formed by nucleotides 3’ to (i.e. downstream of, in the context of the complete sequence of the given nucleotide sequence) the midpoint of the given nucleotide sequence, or a subsequence of this region. By way of illustration, in SEQ ID NO:9, a sequence provided at the 3’ end of SEQ ID NO:9 refers to a nucleotide sequence formed by positions 208 to 414 of SEQ ID NO:9, or a subsequence thereof. In some embodiments, a subsequence of a given nucleotide sequence provided at the 5’ end of the given nucleotide sequence includes at least 5%, e.g. one of at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90% or 100% of the region of the nucleotide sequence formed by nucleotides 5’ to (i.e. upstream of, in the context of the complete sequence of the given nucleotide sequence) the midpoint of the given nucleotide sequence. By way of illustration, a sequence provided at the 5’ end of SEQ ID NO:9 may comprise at least 5%, e.g. one of at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90% or 100% of the region formed by positions 1 to 207 of SEQ ID NO:9. In some embodiments, a subsequence of a given nucleotide sequence provided at the 3’ end of the given nucleotide sequence includes at least 5%, e.g. one of at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90% or 100% of the region of the nucleotide sequence formed by nucleotides 3’ to (i.e. downstream of, in the context of the complete sequence of the given nucleotide sequence) the midpoint of the given nucleotide sequence. By way of illustration, a sequence provided at the 3’ end of SEQ ID NO:9 may comprise at least 5%, e.g. one of at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90% or 100% of the region formed by positions 208 to 414 of SEQ ID NO:9. P37829 In some embodiments, a subsequence of a given nucleotide sequence provided at the 5’ end of the given nucleotide sequence includes one or more nucleotides provided within 25 nucleotides, e.g. within one of 20, 15, 10 or 5 nucleotides, of the 5’ nucleotide of the given nucleotide sequence. In some embodiments, a subsequence of a given nucleotide sequence provided at the 5’ end of the given nucleotide sequence includes the 5’ nucleotide of the given nucleotide sequence. By way of illustration, a sequence provided at the 5’ end of SEQ ID NO:9 may comprise one or more nucleotides provided within positions 1 to 25, e.g. within positions 1 to 20, 1 to 15, 1 to 10, or 1 to 5 of SEQ ID NO:9. By way of illustration, a sequence provided at the 5’ end of SEQ ID NO:9 may comprise position 1 of SEQ ID NO:9. In some embodiments, a subsequence of a given nucleotide sequence provided at the 3’ end of the given nucleotide sequence includes one or more nucleotides provided within 25 nucleotides, e.g. within one of 20, 15, 10 or 5 nucleotides, of the 3’ nucleotide of the given nucleotide sequence. In some embodiments, a subsequence of a given nucleotide sequence provided at the 3’ end of the given nucleotide sequence includes the 3’ nucleotide of the given nucleotide sequence. By way of illustration, a sequence provided at the 3’ end of SEQ ID NO:9 may comprise one or more nucleotides provided within positions 389 to 414, e.g. within positions 394 to 414, 399 to 414, 404 to 414, or 409 to 414 of SEQ ID NO:9. By way of illustration, a sequence provided at the 3’ end of SEQ ID NO:9 may comprise position 414 of SEQ ID NO:9. In some embodiments the second nucleotide sequence comprises a nucleotide sequence having at least 80% sequence identity to SEQ ID NO:7 in the region 5’ to its midpoint. In some embodiments, the second nucleotide sequence comprises a nucleotide sequence having at least 80% sequence identity to SEQ ID NO:8 or SEQ ID NO:377 in the region 3’ to its midpoint. In some embodiments, the nucleotide sequence having at least 80% sequence identity to SEQ ID NO:7 accounts for at least 5%, e.g. one of at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90% or 100% of the region 5’ to the midpoint of the second nucleotide sequence. In some embodiments, the nucleotide sequence having at least 80% sequence identity to SEQ ID NO:8 or SEQ ID NO:377 accounts for at least 5%, e.g. one of at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90% or 100% of the region 3’ to the midpoint of the second nucleotide sequence. In some embodiments the nucleotide sequence having at least 80% sequence identity to SEQ ID NO:7 comprises one or more nucleotides provided within 25, e.g. within positions 20, 15, 10, or 5 nucleotides of the 5’ nucleotide of the second nucleotide sequence. In some embodiments the nucleotide sequence having at least 80% sequence identity to SEQ ID NO:7 comprises the 5’ nucleotide of the second nucleotide sequence. In some embodiments the nucleotide sequence having at least 80% sequence identity to SEQ ID NO:8 or SEQ ID NO:377 comprises one or more nucleotides provided within 25, e.g. within positions 20, 15, 10, or 5 nucleotides of the 3’ nucleotide of the second nucleotide sequence. In some embodiments the nucleotide sequence having at least 80% sequence identity to SEQ ID NO:8 or SEQ ID NO:377 comprises the 3’ nucleotide of the second nucleotide sequence. P37829 An exemplary sequence comprising a nucleotide sequence having at least 80% sequence identity to SEQ ID NO:7 at its 5’ end is SEQ ID NO:9. Positions 1 to 102 of SEQ ID NO:9 correspond to positions 1 to 102 of SEQ ID NO:7. An exemplary sequence comprising a nucleotide sequence having at least 80% sequence identity to SEQ ID NO:8 at its 3’ end is SEQ ID NO:9. Positions 253 to 414 of SEQ ID NO:9 correspond to positions 1 to 162 of SEQ ID NO:8. In some embodiments, the second nucleotide sequence comprises, or consists of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to a nucleotide sequence according to SEQ ID NO:229. Exemplary sequences conforming to the consensus nucleotide sequence of SEQ ID NO:229 include SEQ ID NOs:10 and 228. In some embodiments, the second nucleotide sequence comprises, or consists of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:9. In some embodiments, the second nucleotide sequence comprises, or consists of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:10. In some embodiments, the second nucleotide sequence comprises ‘C’ at the position corresponding to position 5766 of SEQ ID NO:30 (cf. e.g. position 411 of SEQ ID NO:9, position 261 of SEQ ID NO:10). In some embodiments, the second nucleotide sequence consists of fewer than 1044 nucleotides, e.g. one of <1000 nucleotides, <900 nucleotides, <800 nucleotides, <750 nucleotides, <700 nucleotides, <650 nucleotides, <600 nucleotides, <550 nucleotides or <500 nucleotides. In some embodiments, the second nucleotide sequence consists of fewer than 500 nucleotides, e.g. one of <450 nucleotides, <400 nucleotides, <350 nucleotides, <300 nucleotides, <250 nucleotides or <200 nucleotides. In some embodiments, the second nucleotide sequence consists of 1044 nucleotides. In some embodiments, the second nucleotide sequence consists of 414 nucleotides. In some embodiments, the second nucleotide sequence consists of 264 nucleotides. In some embodiments, the second nucleotide sequence consists of 189 nucleotides. In some embodiments, the second nucleotide sequence comprises: (i) a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:7 at its 5’ end; and (ii) a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:8 at its 3’ end; and (iii) comprises ‘C’ at the position corresponding to position 5766 of SEQ ID NO:30; and (iv) consists of fewer than 1044 nucleotides. Examples of such second nucleotide sequences include SEQ ID NOs:9 and 10. P37829 In some embodiments, the second nucleotide sequence comprises: (i) a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:7 at its 5’ end; and (ii) a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:8 at its 3’ end; and (iii) comprises ‘C’ at the position corresponding to position 5766 of SEQ ID NO:30; and (iv) consists of fewer than 500 nucleotides. An example of such a second nucleotide sequence is SEQ ID NO:9. In some embodiments, the second nucleotide sequence comprises: (i) a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:7 at its 5’ end; and (ii) a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:8 at its 3’ end; and (iii) comprises ‘C’ at the position corresponding to position 5766 of SEQ ID NO:30; and (iv) consists of fewer than 300 nucleotides. An example of such a second nucleotide sequence is SEQ ID NO:10. In some embodiments, a polynucleotide according to the present disclosure comprises a nucleotide sequence (e.g. a second nucleotide sequence) comprising, or consisting of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to a nucleotide sequence selected from SEQ ID NOs:9, 10, 228, 238 to 255, 375 and 376. In some embodiments, a polynucleotide according to the present disclosure does not comprise the nucleotide sequence of SEQ ID NO:240. In some embodiments, a polynucleotide according to the present disclosure comprises a nucleotide sequence (e.g. a second nucleotide sequence) comprising, or consisting of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to a nucleotide sequence selected from SEQ ID NOs:9, 10, 228, 238, 239, 241 to 255, 375 and 376. In some embodiments, a polynucleotide according to the present disclosure comprises a nucleotide sequence (e.g. a second nucleotide sequence) comprising, or consisting of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:9. In some embodiments, a polynucleotide according to the present disclosure comprises a nucleotide sequence (e.g. a second nucleotide sequence) comprising, or consisting of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:10. In some embodiments, a polynucleotide according to the present disclosure comprises a nucleotide sequence (e.g. a second nucleotide sequence) comprising, or consisting of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:228. P37829 Third nucleotide sequence The third nucleotide sequence according to the present disclosure comprises, or consists of, a nucleotide sequence which is a variant of human SMN2 exon 7. Accordingly, in some embodiments, the third nucleotide sequence does not consist of, or does not comprise, SEQ ID NO:12. In some embodiments, the third nucleotide sequence comprises, or consists of, a nucleotide sequence having <100% sequence identity to SEQ ID NO:12. In some embodiments, the third nucleotide sequence comprises, or consists of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to a nucleotide sequence according to SEQ ID NO:11. It will be appreciated that ‘a nucleotide sequence according to SEQ ID NO:11’ refers to a nucleotide sequence conforming to the consensus nucleotide sequence of SEQ ID NO:11. Exemplary sequences conforming to the consensus nucleotide sequence of SEQ ID NO:11 include SEQ ID NOs:13 and 14. In some embodiments, the third nucleotide sequence comprises, or consists of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to a nucleotide sequence according to SEQ ID NO:26. It will be appreciated that ‘a nucleotide sequence according to SEQ ID NO:26’ refers to a nucleotide sequence conforming to the consensus nucleotide sequence of SEQ ID NO:26. Exemplary sequences conforming to the consensus nucleotide sequence of SEQ ID NO:26 include SEQ ID NOs:13 and 27. In some embodiments, the third nucleotide sequence comprises, or consists of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to a nucleotide sequence according to SEQ ID NO:225. Exemplary sequences conforming to the consensus nucleotide sequence of SEQ ID NO:225 include SEQ ID NOs:223 and 224. In some embodiments, the third nucleotide sequence comprises, or consists of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to a nucleotide sequence according to SEQ ID NO:226. In some embodiments, the third nucleotide sequence comprises, or consists of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:13. In some embodiments, the third nucleotide sequence comprises, or consists of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:14. In some embodiments, the third nucleotide sequence comprises, or consists of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:27. P37829 In some embodiments, the third nucleotide sequence comprises ‘A’ at the position corresponding to position 2 of SEQ ID NO:12 (cf. e.g. position 2 of SEQ ID NOs:11, 13, 14, 26 and 27). In some embodiments, the third nucleotide sequence comprises insertion of ‘GCCACC’ after the position corresponding to position 6 of SEQ ID NO:12 (cf. e.g. positions 7 to 12 of SEQ ID NO:14). In some embodiments, the third nucleotide sequence comprises ‘TG’ at the positions corresponding to positions 8 to 9 of SEQ ID NO:12 (cf. e.g. positions 14 and 15 of SEQ ID NO:14). In some embodiments, the third nucleotide sequence comprises insertion of ‘A’ after the position corresponding to position 48 of SEQ ID NO:12 (cf. e.g. position 49 of SEQ ID NO:13, position 55 of SEQ ID NO:14). In some embodiments, the third nucleotide sequence comprises ‘G’ at the position corresponding to position 24 of SEQ ID NO:12. In some embodiments, the third nucleotide sequence comprises deletion of the nucleotide at the position corresponding to position 20 of SEQ ID NO:12. In some embodiments, the third nucleotide sequence comprises ‘T’ at the position corresponding to position 27 of SEQ ID NO:12. In some embodiments, the third nucleotide sequence comprises ‘T’ at the position corresponding to position 28 of SEQ ID NO:12. In some embodiments, the third nucleotide sequence comprises ‘G’ at the position corresponding to position 21 of SEQ ID NO:12. In some embodiments, the third nucleotide sequence comprises ‘A’ at the position corresponding to position 29 of SEQ ID NO:12. In some embodiments, the third nucleotide sequence comprises ‘T’ at the position corresponding to position 21 of SEQ ID NO:12. In some embodiments, the third nucleotide sequence comprises ‘A’ at the position corresponding to position 31 of SEQ ID NO:12, and comprises ‘A’ at the position corresponding to position 34 of SEQ ID NO:12. In some embodiments, the third nucleotide sequence comprises deletion of the positions corresponding to positions 9 to 20 of SEQ ID NO:12. In some embodiments, the third nucleotide sequence comprises deletion of the positions corresponding to positions 33 to 41 of SEQ ID NO:12. In some embodiments, the third nucleotide sequence comprises ‘CAC’ at the positions corresponding to positions 34 to 36 of SEQ ID NO:12. In some embodiments, the third nucleotide sequence comprises insertion of ‘G’ after the position corresponding to position 39 of SEQ ID NO:12. In some embodiments, the third nucleotide sequence comprises ‘GC’ at the positions corresponding to positions 47 to 48 of SEQ ID NO:12. In some embodiments, the third nucleotide sequence comprises insertion of ‘CACCATG’ after the position corresponding to position 48 of SEQ ID NO:12. In some embodiments, the third nucleotide sequence comprises ‘C’ at the position corresponding to position 48 of SEQ ID NO:12. In some embodiments, the third nucleotide sequence comprises insertion of ‘AA’ after the position corresponding to position 48 of SEQ ID NO:12. In some embodiments, the third nucleotide sequence comprises ‘CAT’ at the positions corresponding to positions 49 to 51 of SEQ ID NO:12. In some embodiments, the third nucleotide sequence comprises ‘GCC’ at the positions corresponding to positions 46 to 48 of SEQ ID NO:12. In some embodiments, the third nucleotide sequence comprises ‘CCA’ at the positions corresponding to positions 49 to 51 of SEQ ID NO:12. In some embodiments, the third nucleotide sequence comprises insertion of ‘T’ after the position corresponding to position 51 of SEQ ID NO:12. In some embodiments, the third nucleotide sequence comprises ‘GC’ at the positions corresponding to positions 39 to 40 of SEQ P37829 ID NO:12. In some embodiments, the third nucleotide sequence comprises insertion of ‘CA’ after the position corresponding to position 40 of SEQ ID NO:12. In some embodiments, the third nucleotide sequence comprises ‘ATG’ at the positions corresponding to positions 43 to 45 of SEQ ID NO:12, and deletion of the position corresponding to position 46 of SEQ ID NO:12. In some embodiments, the third nucleotide sequence comprises insertion of ‘GCCACCATG’ after the position corresponding to position 9 of SEQ ID NO:12. In some embodiments, the third nucleotide sequence comprises insertion of ‘AGCACCATG’ after the position corresponding to position 15 of SEQ ID NO:12. In some embodiments, the third nucleotide sequence comprises ‘G’ at the position corresponding to position 16 of SEQ ID NO:12. In some embodiments, the third nucleotide sequence comprises insertion of ‘CACCATG’ after the position corresponding to position 15 of SEQ ID NO:12. In some embodiments, the third nucleotide sequence comprises insertion of ‘ATG’ after the position corresponding to position 15 of SEQ ID NO:12. In some embodiments, the third nucleotide sequence comprises insertion of ‘ATG’ after the position corresponding to position 21 of SEQ ID NO:12. In some embodiments, the third nucleotide sequence comprises insertion of ‘GG’ after the position corresponding to position 48 of SEQ ID NO:12. In some embodiments, the third nucleotide sequence comprises insertion of ‘AT’ after the position corresponding to position 30 of SEQ ID NO:12. In some embodiments, the third nucleotide sequence comprises ‘G’ at the position corresponding to position 31 of SEQ ID NO:12. In some embodiments, the third nucleotide sequence comprises insertion of ‘G’ after the position corresponding to position 33 of SEQ ID NO:12. In some embodiments, the third nucleotide sequence comprises insertion of ‘A’ after the position corresponding to position 43 of SEQ ID NO:12. In some embodiments, the third nucleotide sequence comprises ‘GG’ at the positions corresponding to positions 45 and 46 of SEQ ID NO:12. In some embodiments, the third nucleotide sequence comprises insertion of ‘AT’ after the position corresponding to position 52 of SEQ ID NO:12. In some embodiments, the third nucleotide sequence comprises deletion of the positions corresponding to positions 49 and 50 of SEQ ID NO:12. In some embodiments, the third nucleotide sequence comprises ‘G’ at the position corresponding to position 51 of SEQ ID NO:12. In some embodiments, the third nucleotide sequence comprises ‘G’ at the position corresponding to position 40 of SEQ ID NO:12. In some embodiments, the third nucleotide sequence comprises ‘A’ at the position corresponding to position 35 of SEQ ID NO:12. In some embodiments, the third nucleotide sequence comprises insertion of ‘A’ after the position corresponding to position 39 of SEQ ID NO:12. In some embodiments, the third nucleotide sequence comprises ‘G’ at the position corresponding to position 41 of SEQ ID NO:12. In some embodiments, the third nucleotide sequence comprises ‘C’ at the position corresponding to position 43 of SEQ ID NO:12. In some embodiments, the third nucleotide sequence comprises insertion of ‘ATG’ after the position corresponding to position 42 of SEQ ID NO:12. In some embodiments, the third nucleotide sequence comprises insertion of ‘TG’ after the position corresponding to position 45 of SEQ ID NO:12. In some embodiments, the third nucleotide sequence comprises insertion of ‘ATGGA’ after the position corresponding to position 44 of SEQ ID NO:12. In some embodiments, the third nucleotide sequence comprises ‘A’ at the position corresponding to position 44 of SEQ ID NO:12. In some embodiments, the third nucleotide sequence comprises ‘G’ at the position corresponding to position 49 of SEQ ID NO:12. In some embodiments, the third nucleotide sequence comprises deletion of the position corresponding to position 50 of SEQ ID NO:12. In some embodiments, the third nucleotide sequence comprises ‘A’ at the position corresponding to position 48 of SEQ ID NO:12. In some embodiments, the third nucleotide sequence comprises ‘G’ at the position corresponding P37829 to position 50 of SEQ ID NO:12. In some embodiments, the third nucleotide sequence comprises ‘G’ at the position corresponding to position 44 of SEQ ID NO:12. In some embodiments, the third nucleotide sequence comprises deletion of the position corresponding to position 49 of SEQ ID NO:12. In some embodiments, the third nucleotide sequence comprises deletion of the positions corresponding to positions 42 to 44 of SEQ ID NO:12. In some embodiments, the third nucleotide sequence comprises insertion of ‘G’ after the position corresponding to position 39 of SEQ ID NO:12. In some embodiments, the third nucleotide sequence comprises deletion of the position corresponding to position 48 of SEQ ID NO:12. In some embodiments, the third nucleotide sequence comprises insertion of ‘GA’ after the position corresponding to position 48 of SEQ ID NO:12. In some embodiments, the third nucleotide sequence comprises, or consists of: (i) a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to a nucleotide sequence according to SEQ ID NO:11; and (ii) comprises ‘A’ at the position corresponding to position 2 of SEQ ID NO:12; and (iii) comprises insertion of ‘A’ after the position corresponding to position 48 of SEQ ID NO:12. An example of such a third nucleotide sequence is SEQ ID NO:13. In some embodiments, the third nucleotide sequence comprises, or consists of: (i) a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to a nucleotide sequence according to SEQ ID NO:11; and (ii) comprises ‘A’ at the position corresponding to position 2 of SEQ ID NO:12; and (iii) comprises insertion of ‘A’ after the position corresponding to position 48 of SEQ ID NO:12; and (iv) comprises insertion of ‘GCCACC’ after the position corresponding to position 6 of SEQ ID NO:12; and (v) comprises ‘TG’ at the positions corresponding to positions 8 and 9 of SEQ ID NO:12. An example of such a third nucleotide sequence is SEQ ID NO:14. In some embodiments, the third nucleotide sequence comprises, or consists of: (i) a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to a nucleotide sequence according to SEQ ID NO:26; and (ii) comprises ‘A’ at the position corresponding to position 2 of SEQ ID NO:12; and (iii) comprises deletion of the position corresponding to position 20 of SEQ ID NO:12; and (iv) comprises insertion of ‘A’ after the position corresponding to position 48 of SEQ ID NO:12. An example of such a third nucleotide sequence is SEQ ID NO:27. In some embodiments, a polynucleotide according to the present disclosure comprises a nucleotide sequence (e.g. a third nucleotide sequence) comprising, or consisting of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to a nucleotide sequence selected from SEQ ID NOs:13, 14, 27, 223, 224 and 256 to 329. In some embodiments, a polynucleotide according to the present disclosure does not comprise the nucleotide sequence of SEQ ID NO:13. In some embodiments, a polynucleotide according to the present P37829 disclosure comprises a nucleotide sequence (e.g. a third nucleotide sequence) comprising, or consisting of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to a nucleotide sequence selected from SEQ ID NOs:14, 27, 223, 224 and 256 to 329. In some embodiments, a polynucleotide according to the present disclosure comprises a nucleotide sequence (e.g. a third nucleotide sequence) comprising, or consisting of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:13. In some embodiments, a polynucleotide according to the present disclosure comprises a nucleotide sequence (e.g. a third nucleotide sequence) comprising, or consisting of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:14. In some embodiments, a polynucleotide according to the present disclosure comprises a nucleotide sequence (e.g. a third nucleotide sequence) comprising, or consisting of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:27. In some embodiments, a polynucleotide according to the present disclosure comprises a nucleotide sequence (e.g. a third nucleotide sequence) comprising, or consisting of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:223. In some embodiments, a polynucleotide according to the present disclosure comprises a nucleotide sequence (e.g. a third nucleotide sequence) comprising, or consisting of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:224. Fourth nucleotide sequence The fourth nucleotide sequence according to the present disclosure comprises, or consists of, a nucleotide sequence which is a variant of human SMN2 intron 7. Accordingly, in some embodiments, the fourth nucleotide sequence does not consist of, or does not comprise, SEQ ID NO:18. In some embodiments, the fourth nucleotide sequence comprises, or consists of, a nucleotide sequence having <100% sequence identity to SEQ ID NO:18. In some embodiments, the fourth nucleotide sequence comprises a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to a nucleotide sequence according to SEQ ID NO:380 at its 5’ end. It will be appreciated that ‘a nucleotide sequence according to SEQ ID NO:380’ refers to a nucleotide sequence conforming to the consensus nucleotide sequence of SEQ ID NO:380. Exemplary sequences conforming to the consensus nucleotide sequence of SEQ ID NO:380 include SEQ ID NO:15 and SEQ ID NO:379. In some embodiments, the fourth nucleotide sequence comprises a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:15 at its 5’ end. In some embodiments, the fourth nucleotide sequence P37829 comprises a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:379 at its 5’ end. In some embodiments, the fourth nucleotide sequence comprises a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:16 at its 3’ end. In some embodiments, the fourth nucleotide sequence comprises a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:15 at its 5’ end, and comprises a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:16 at its 3’ end. In some embodiments, the fourth nucleotide sequence comprises a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:379 at its 5’ end, and comprises a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:16 at its 3’ end. In some embodiments the fourth nucleotide sequence comprises a nucleotide sequence having at least 80% sequence identity to SEQ ID NO:15 or SEQ ID NO:379 in the region 5’ to its midpoint. In some embodiments, the fourth nucleotide sequence comprises a nucleotide sequence having at least 80% sequence identity to SEQ ID NO:16 in the region 3’ to its midpoint. In some embodiments, the nucleotide sequence having at least 80% sequence identity to SEQ ID NO:15 or SEQ ID NO:379 accounts for at least 5%, e.g. one of at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90% or 100% of the region 5’ to the midpoint of the fourth nucleotide sequence. In some embodiments, the nucleotide sequence having at least 80% sequence identity to SEQ ID NO:16 accounts for at least 5%, e.g. one of at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90% or 100% of the region 3’ to the midpoint of the fourth nucleotide sequence. In some embodiments the nucleotide sequence having at least 80% sequence identity to SEQ ID NO:15 or SEQ ID NO:379 comprises one or more nucleotides provided within 25, e.g. within positions 20, 15, 10, or 5 nucleotides of the 5’ nucleotide of the fourth nucleotide sequence. In some embodiments the nucleotide sequence having at least 80% sequence identity to SEQ ID NO:15 or SEQ ID NO:379 comprises the 5’ nucleotide of the fourth nucleotide sequence. In some embodiments the nucleotide sequence having at least 80% sequence identity to SEQ ID NO:16 comprises one or more nucleotides provided within 25, e.g. within positions 20, 15, 10, or 5 nucleotides of the 3’ nucleotide of the fourth nucleotide sequence. In some embodiments the nucleotide sequence having at least 80% sequence identity to SEQ ID NO:16 comprises the 3’ nucleotide of the fourth nucleotide sequence. An exemplary sequence comprising a nucleotide sequence having at least 80% sequence identity to SEQ ID NO:15 at its 5’ end is SEQ ID NO:17. Positions 1 to 102 of SEQ ID NO:17 correspond to positions 1 to 102 of SEQ ID NO:15. P37829 An exemplary sequence comprising a nucleotide sequence having at least 80% sequence identity to SEQ ID NO:16 at its 3’ end is SEQ ID NO:18. Positions 295 to 444 of SEQ ID NO:18 correspond to positions 1 to 150 of SEQ ID NO:16. In some embodiments, the fourth nucleotide sequence comprises, or consists of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:16. In some embodiments, the fourth nucleotide sequence comprises, or consists of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:17. In some embodiments, the fourth nucleotide sequence comprises, or consists of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:18. In some embodiments, the fourth nucleotide sequence consists of fewer than 444 nucleotides, e.g. one of <425 nucleotides, <400 nucleotides, <350 nucleotides, <300 nucleotides, <250 nucleotides or <200 nucleotides. In some embodiments, the fourth nucleotide sequence consists of fewer than 255 nucleotides. In some embodiments, the fourth nucleotide sequence consists of 252 nucleotides. In some embodiments, the fourth nucleotide sequence consists of 177 nucleotides. In some embodiments, the fourth nucleotide sequence consists of greater than 444 nucleotides, e.g. one of >450 nucleotides, >475 nucleotides or >500 nucleotides. In some embodiments, the fourth nucleotide sequence consists of 508 nucleotides. In some embodiments, the fourth nucleotide sequence comprises ‘C’ at the position corresponding to position 441 of SEQ ID NO:18. In some embodiments, the fourth nucleotide sequence comprises ‘T’ at the position corresponding to position 441 of SEQ ID NO:18. In some embodiments, the fourth nucleotide sequence comprises ‘TT’ at the positions corresponding to positions 436 and 437 of SEQ ID NO:18. In some embodiments, the fourth nucleotide sequence comprises ‘TCCTC’ at the positions corresponding to positions 11 to 15 of SEQ ID NO:18. In some embodiments, the fourth nucleotide sequence comprises insertion of ‘TTT’ after the position corresponding to position 10 of SEQ ID NO:18. In some embodiments, the fourth nucleotide sequence comprises insertion of ‘CCC’ after the position corresponding to position 10 of SEQ ID NO:18. In some embodiments, the fourth nucleotide sequence comprises: (i) a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:15 at its 5’ end; and (ii) a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:16 at its 3’ end; and (iii) consists of fewer than 500 nucleotides. Examples of such fourth nucleotide sequences include SEQ ID NOs:17 and 18. In some embodiments, the fourth nucleotide sequence comprises: (i) a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or P37829 100%) sequence identity to SEQ ID NO:15 at its 5’ end; and (ii) a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:16 at its 3’ end; and (iii) consists of fewer than 255 nucleotides. An example of such a fourth nucleotide sequence is SEQ ID NO:17. In some embodiments, a polynucleotide according to the present disclosure comprises a nucleotide sequence (e.g. a fourth nucleotide sequence) comprising, or consisting of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to a nucleotide sequence selected from SEQ ID NOs:18, 227, 330 to 370 and 381. In some embodiments, a polynucleotide according to the present disclosure does not comprise the nucleotide sequence of SEQ ID NO:337. In some embodiments, a polynucleotide according to the present disclosure comprises a nucleotide sequence (e.g. a third nucleotide sequence) comprising, or consisting of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to a nucleotide sequence selected from SEQ ID NOs:18, 227, 330 to 336, 338 to 370 and 381. In some embodiments, a polynucleotide according to the present disclosure comprises a nucleotide sequence (e.g. a fourth nucleotide sequence) comprising, or consisting of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:18. In some embodiments, a polynucleotide according to the present disclosure comprises a nucleotide sequence (e.g. a fourth nucleotide sequence) comprising, or consisting of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:227. Fifth nucleotide sequence The fifth nucleotide sequence according to the present disclosure comprises, or consists of, a nucleotide sequence which is a variant of human SMN2 exon 8. Accordingly, in some embodiments, the fifth nucleotide sequence does not consist of, or does not comprise, SEQ ID NO:32. In some embodiments, the fifth nucleotide sequence comprises, or consists of, a nucleotide sequence having <100% sequence identity to SEQ ID NO:32. In some embodiments, the fifth nucleotide sequence consists of the dinucleotide ‘GA’, ‘TG’ or ‘TT’. In some embodiments, the fifth nucleotide sequence consists of the dinucleotide ‘GA’. In some embodiments, the fifth nucleotide sequence consists of the dinucleotide ‘TG’. In some embodiments, the fifth nucleotide sequence consists of the dinucleotide ‘TT’. In some embodiments, the fifth nucleotide sequence consists of the trinucleotide ‘GAG’. In some embodiments, the fifth nucleotide sequence consists of the nucleotide ‘A’. P37829 In some embodiments, the fifth nucleotide sequence encodes a polypeptide of interest (e.g. as described hereinbelow). In some embodiments, the fifth nucleotide sequence encodes a polypeptide of interest, and comprises ‘GA’, 'TG' or ‘TT’ at positions 1 and 2. In some embodiments, the fifth nucleotide sequence encodes a polypeptide of interest, and comprises ‘GA’ at positions 1 and 2. In some embodiments, the fifth nucleotide sequence encodes a polypeptide of interest, and comprises ‘TG’ at positions 1 and 2. In some embodiments, the fifth nucleotide sequence encodes a polypeptide of interest, and comprises ‘TT’ at positions 1 and 2. In some embodiments, the fifth nucleotide sequence encodes a polypeptide of interest, and comprises ‘GAG’ at positions 1 to 3. In some embodiments, the fifth nucleotide sequence comprises, or consists of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to a nucleotide sequence according to SEQ ID NO:19. It will be appreciated that ‘a nucleotide sequence according to SEQ ID NO:19’ refers to a nucleotide sequence conforming to the consensus nucleotide sequence of SEQ ID NO:19. Exemplary sequences conforming to the consensus nucleotide sequence of SEQ ID NO:19 include SEQ ID NOs:20 and 21. In some embodiments, the fifth nucleotide sequence comprises, or consists of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:20. In some embodiments, the fifth nucleotide sequence comprises, or consists of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:21. In some embodiments, the fifth nucleotide sequence comprises ‘GA’ at the positions corresponding to positions 1 and 2 of SEQ ID NO:32 (cf. e.g. positions 1 and 2 of SEQ ID NO:20). In some embodiments, the fifth nucleotide sequence comprises ‘TG’ at the positions corresponding to positions 1 and 2 of SEQ ID NO:32 (cf. e.g. positions 1 and 2 of SEQ ID NO:21). In some embodiments, the fifth nucleotide sequence comprises fewer than 577 nucleotides. In some embodiments the fifth nucleotide sequence consists of <500 nucleotides, e.g. one of <400 nucleotides, <300 nucleotides, <200 nucleotides, <100 nucleotides or <50 nucleotides. In some embodiments, the fifth nucleotide sequence comprises fewer than 25 nucleotides, e.g. one of <20 nucleotides, <15 nucleotides, <10 nucleotides or <5 nucleotides. In some embodiments, the fifth nucleotide sequence comprises 23 nucleotides. In some embodiments, the fifth nucleotide sequence comprises 2 nucleotides. P37829 In some embodiments, the fifth nucleotide sequence comprises 11 nucleotides. In some embodiments, the fifth nucleotide sequence comprises 8 nucleotides. In some embodiments, the fifth nucleotide sequence comprises 5 nucleotides. In some embodiments, the fifth nucleotide sequence comprises, or consists of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥95% or 100%) sequence identity to positions 1 to 23 of SEQ ID NO:32. In some embodiments, the fifth nucleotide sequence comprises insertion of ‘G’ after the position corresponding to position 2 of SEQ ID NO:32. In some embodiments, the fifth nucleotide sequence comprises, or consists of, a nucleotide sequence having at least 80% (e.g. ≥90% or 100%) sequence identity to positions 1 to 11 of SEQ ID NO:32. In some embodiments, the fifth nucleotide sequence comprises, or consists of, a nucleotide sequence having at least 80% (e.g.100%) sequence identity to positions 1 to 8 of SEQ ID NO:32. In some embodiments, the fifth nucleotide sequence comprises, or consists of, a nucleotide sequence having at least 80% (e.g.100%) sequence identity to positions 1 to 5 of SEQ ID NO:32. In some embodiments, the fifth nucleotide sequence comprises, or consists of, positions 1 and 2 of SEQ ID NO:32. In some embodiments, the fifth nucleotide sequence comprises ‘A’ at the position corresponding to position 1 of SEQ ID NO:32. In some embodiments, the fifth nucleotide sequence comprises insertion of ‘T’ after the position corresponding to position 1 of SEQ ID NO:32. In some embodiments, the fifth nucleotide sequence comprises ‘G’ at the position corresponding to position 3 of SEQ ID NO:32. In some embodiments, the fifth nucleotide sequence comprises, or consists of: (i) a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:19; and (ii) comprises ‘GA’ at the positions corresponding to positions 1 and 2 of SEQ ID NO:32. An example of such a fifth nucleotide sequence is SEQ ID NO:20. In some embodiments, the fifth nucleotide sequence comprises, or consists of: (i) a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:19; and (ii) comprises ‘TG’ at the positions corresponding to positions 1 and 2 of SEQ ID NO:32. An example of such a fifth nucleotide sequence is SEQ ID NO:21. In some embodiments, a polynucleotide according to the present disclosure comprises a nucleotide sequence (e.g. a fifth nucleotide sequence) comprising, or consisting of: the dinucleotide ‘TG’, the dinucleotide ‘GA’, the dinucleotide ‘TT’, the trinucleotide ‘GAG’, the nucleotide ‘A’, or a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to a nucleotide sequence selected from SEQ ID NOs:20, 21 and 371 to 374. P37829 In some embodiments, a polynucleotide according to the present disclosure does not comprise the nucleotide sequence of SEQ ID NO:20. In some embodiments, a polynucleotide according to the present disclosure comprises a nucleotide sequence (e.g. a fifth nucleotide sequence) comprising, or consisting of: the dinucleotide ‘TG’, the dinucleotide ‘GA’, the dinucleotide ‘TT’, the trinucleotide ‘GAG’, the nucleotide ‘A’, or a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to a nucleotide sequence selected from SEQ ID NOs:21 and 371 to 374. In some embodiments, a polynucleotide according to the present disclosure comprises a nucleotide sequence (e.g. a fifth nucleotide sequence) comprising, or consisting of the dinucleotide ‘TG’. In some embodiments, a polynucleotide according to the present disclosure comprises a nucleotide sequence (e.g. a fifth nucleotide sequence) comprising, or consisting of the dinucleotide ‘GA’. In some embodiments, a polynucleotide according to the present disclosure comprises a nucleotide sequence (e.g. a fifth nucleotide sequence) comprising, or consisting of the dinucleotide ‘TT’. In some embodiments, a polynucleotide according to the present disclosure comprises a nucleotide sequence (e.g. a fifth nucleotide sequence) comprising, or consisting of the trinucleotide ‘GAG’. In some embodiments, a polynucleotide according to the present disclosure comprises a nucleotide sequence (e.g. a fifth nucleotide sequence) comprising, or consisting of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:20. In some embodiments, a polynucleotide according to the present disclosure comprises a nucleotide sequence (e.g. a fifth nucleotide sequence) comprising, or consisting of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:21. Nucleotide sequences encoding a polypeptide of interest In some embodiments, the fifth nucleotide sequence according to the present disclosure comprises, or consists of, a nucleotide sequence encoding a polypeptide of interest. Where present, the sixth nucleotide sequence according to the present disclosure comprises, or consists of, a nucleotide sequence encoding a polypeptide of interest. A polypeptide of interest may be any polypeptide. In some embodiments, a polypeptide of interest according to the present disclosure may be an antigen- binding polypeptide, an aptamer, an antigen-binding polypeptide complex, an antibody or an antigen- binding fragment or derivative thereof, an Fc fusion protein, an anticoagulant, a blood factor, a bone morphogenetic protein, a decoy receptor for a ligand, a decoy ligand for a receptor, an enzyme, a growth factor, a hormone, an interferon, an interleukin, a thrombolytic, a transcription factor, an epigenetic modifier, a constituent protein of a site-specific nuclease nucleic acid editing system (e.g. a CRISPR / Cas9 system, a CRISPR / Cpf1 system, a CRISPR / C2c1 system, a CRISPR / C2c2 system, a CRISPR / C2c3 system, a ZFN system or a TALEN system), a constituent protein of a ribonucleoprotein, or a viral protein (e.g. a capsid protein or a viral enzyme). P37829 In some embodiments, a polypeptide of interest according to the present disclosure may be an antigen- binding polypeptide or an antigen-binding polypeptide complex. In some embodiments, a polypeptide of interest may be a chimeric antigen-receptor (CAR). In some embodiments, a polypeptide of interest is a polypeptide suitable for use in therapy or prophylaxis of a disease / condition. In some embodiments, a polypeptide of interest is a detectable polypeptide or a polypeptide having detectable activity. A polypeptide suitable for use in therapy or prophylaxis of a disease / condition may be any polypeptide whose administration is useful for the treatment or prevention of a disease / condition. In some embodiments, a polypeptide suitable for use in therapy or prophylaxis of a disease / condition may be a polypeptide for which deficiency thereof is positively associated with, or implicated in the pathology of, a disease or condition. By way of illustration, in some embodiments, the polypeptide of interest may be MeCP2. Deficiency of MeCP2 is associated with Rett syndrome. In some embodiments, a polypeptide suitable for use in therapy or prophylaxis of a disease / condition may be a polypeptide which inhibits the expression and / or activity of a factor whose expression or activity is positively associated with, or implicated in the pathology of, a disease or condition. A detectable polypeptide may be or comprise a fluorescent polypeptide. Fluorescent polypeptides include green fluorescent protein and variants thereof (e.g. enhanced green fluorescent protein), yellow fluorescent protein (e.g. citrine), red fluorescent protein and variants thereof (e.g. mOrange, mCherry), blue fluorescent protein and variants thereof (e.g. TagBFP), cyan fluorescent protein and variants thereof (e.g. mTurquoise, cerulean), allophycocyanin, phycocyanin, phycoerythrin and phycoerythrocyanin. A detectable polypeptide may be or comprise an epitope tag. Epitope tags include e.g. His, (e.g.6XHis), FLAG, c-Myc, StrepTag, haemagglutinin, E, calmodulin-binding protein (CBP), glutathione-s-transferase (GST), maltose-binding protein (MBP), thioredoxin, S-peptide, T7 peptide, SH2 domain, avidin, streptavidin, and haptens (e.g. biotin, digoxigenin, dinitrophenol). A polypeptide having detectable activity may be or comprise an enzymatic moiety. Enzymatic moieties include e.g. luciferases, glucose oxidases, galactosidases (e.g. beta-galactosidase), glucorinidases, phosphatases (e.g. alkaline phosphatase), peroxidases (e.g. horseradish peroxidase) and cholinesterases. A polypeptide of interest expressed from a polynucleotide of the present disclosure may additionally comprises one or more extraneous amino acids added at the N-terminus of the polypeptide, i.e. immediately upstream of the amino acid sequence of the polypeptide of interest. Such extraneous amino acids may be characterised as forming an N-terminal tag on the polypeptide of interest. It may be desirable to minimise the size of, or completely remove, such extraneous amino acids / N-terminal tags on the polypeptide of interest. In some embodiments, the N-terminal tag consists of fewer than 50 amino acids, e.g. one of ≤40 amino acids, ≤30 amino acids, ≤25 amino acids, ≤20 amino acids, ≤15 amino acids, ≤10 amino acids, ≤9 amino acids, ≤8 amino acids, ≤7 amino acids, ≤6 amino acids, ≤5 amino acids, ≤4 amino acids, ≤3 amino acids, ≤2 amino acids or 1 amino acid. In some embodiments, the polypeptide of interest lacks an N-terminal tag. In some embodiments, the polypeptide of the present disclosure comprises one or more cleavage sites. A cleavage site refers to a sequence of amino acids that acts as a substrate for an enzyme capable of cleaving peptide bonds. Many such cleavage sites are known to, and can be employed by, the person skilled in the art of molecular biology. In some embodiments, the cleavage sequence comprises an autocleavage site. Autocleavage sites include the 2A cleavage sequence from Picornavirus ‘NPGP’, which is cleaved at ’G / P’. Further autocleavage sites are described e.g. in Kim et al., PLoS ONE (2011) 6: e18556 (hereby incorporated by reference in its entirety), and include e.g. T2A, E2A, P2A and F2A cleavage sites. The amino acid sequences of T2A, E2A, P2A and F2A cleavage sites are shown in SEQ ID NOs: 107, 108, 109 and 110, respectively. A cleavage site may be included in a polypeptide according to the present disclosure to provide for removal of extraneous amino acids added at the N-terminus of the polypeptide, i.e. immediately upstream of the amino acid sequence of the polypeptide of interest. That is, a cleavage site may be included for the removal of an N-terminal tag as described hereinabove. Accordingly, in some embodiments, a polypeptide according to the present disclosure comprises a cleavage site adjacent to (i.e. in the amino acid sequence of the polypeptide, e.g. immediately downstream of) extraneous amino acid(s), e.g. extraneous amino acid(s) forming an N-terminal tag. In some embodiments, a cleavage site according to the present disclosure is a 2A cleavage site, e.g. selected from a T2A, E2A, P2A and F2A cleavage site. In some embodiments, the cleavage site is a T2A cleavage site. In some embodiments, a polypeptide according to the present disclosure comprises an amino acid sequence having at least 60%, preferably one of ≥70%, ≥75%, ≥80%, ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100% amino acid sequence identity to SEQ ID NO:107, 108, 109 or 110. In some embodiments, a nucleotide sequence encoding a polypeptide of interest according to the present disclosure comprises, or consists of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:213 or 217. Further nucleotide sequences of the polynucleotide Polynucleotides according to the present disclosure may comprise additional nucleotide sequences and / or sequence features in addition to the first, second, third, fourth, fifth and / or sixth nucleotide sequences as described hereinabove. The polynucleotides of the present disclosure comprise a start codon 5’ to (i.e. upstream of, in the context of the nucleotide sequence of the polynucleotide) the nucleotide sequence encoding a polypeptide of interest. The start codon is preferably the trinucleotide ‘ATG’. In some embodiments, a start codon is provided in the polynucleotide such that following splicing (e.g. where the polynucleotide is a polyribonucleotide, or splicing of a polyribonucleotide transcribed from the polynucleotide where the polynucleotide is a polydeoxyribonucleotide), the start codon is provided in the mature mRNA molecule in such a way as to serve as the initiator codon for translation of the polypeptide of interest (encoded by the fifth or sixth nucleotide sequence). In some embodiments, the splicing referred to in the preceding paragraph is splicing performed in the presence of a splicing modifier (e.g. as described herein). By way of illustration, splicing of the polyribonucleotide having the nucleotide sequence of SEQ ID NO:22 in the presence of RG7800 / RG76196 results in the production of a mature mRNA molecule comprising an initiator codon for translation of a polypeptide of interest. In some embodiments, the splicing referred to in the preceding paragraph is splicing performed in the absence of a splicing modifier (e.g. as described herein). By way of illustration, splicing of the polyribonucleotide having the nucleotide sequence of SEQ ID NO:28 in the absence of a splicing modifier results in the production of a mature mRNA molecule comprising an initiator codon for translation of a polypeptide of interest. In some embodiments, the polynucleotide further comprises a Kozak sequence. In preferred embodiments, the Kozak sequence is provided immediately upstream of the start codon for initiating translation of the polypeptide of interest. In some embodiments, the Kozak sequence consists of a nucleotide sequence conforming to the consensus of SEQ ID NO:33. In some embodiments, the Kozak sequence consists of SEQ ID NO:34. In some embodiments, the polynucleotide comprises a nucleotide sequence consisting of SEQ ID NO:35 5’ to the nucleotide sequence encoding a polypeptide of interest. In some embodiments, SEQ ID NO:35 is provided in the polynucleotide such that following splicing (e.g. where the polynucleotide is a polyribonucleotide, or splicing of a polyribonucleotide transcribed from the polynucleotide where the polynucleotide is a polydeoxyribonucleotide), the start codon of SEQ ID NO:35 is provided in the mature mRNA molecule in such a way as to serve as the initiator codon for translation of the polypeptide of interest (encoded by the fifth or sixth nucleotide sequence). In some embodiments, the splicing referred to in the preceding paragraph is splicing performed in the presence of a splicing modifier (e.g. as described herein). In some embodiments, the splicing referred to in the preceding paragraph is splicing performed in the absence of a splicing modifier (e.g. as described herein). In some embodiments, the polynucleotide further comprises a promoter sequence. The promoter sequence is preferably 5’ to the first nucleotide sequence. In some embodiments, the polynucleotide P37829 further comprises one or more enhancer sequences. The one or more enhancer sequences are preferably 5’ to the first nucleotide sequence. In some embodiments, the polynucleotide further comprises a stop codon. The stop codon is preferably provided immediately 3’ to (i.e. downstream of, in the context of the nucleotide sequence of the polynucleotide) the trinucleotide encoding the terminal amino acid of the polypeptide encoded by the fifth or sixth nucleotide sequence. In some embodiments, the polynucleotide further comprises a polyadenylation signal sequence. In preferred embodiments, the polyadenylation signal sequence is provided 3’ to (i.e. downstream of, in the context of the nucleotide sequence of the polynucleotide) the nucleotide sequence encoding a polypeptide of interest. In some embodiments, the polynucleotide further comprises a terminator sequence. The terminator sequence is preferably 3’ to the nucleotide sequence encoding a polypeptide of interest (and 3’ to the polyadenylation signal sequence, when present). In preferred embodiments, the constituent nucleotide sequences of the polynucleotides (i.e. the first, second, third, fourth, fifth and / or sixth nucleotide sequences as described hereinabove) are provided immediately adjacent to one another. However, in some embodiments, the polynucleotide further comprises one or more linker nucleotide sequences between one or more of the constituent nucleotide sequences of the polynucleotide. Linker nucleotide sequences may comprise, or consist of, 1-10, e.g. one of 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1- 3, or 1-2 nucleotides. Where a polynucleotide according to the present disclosure comprises one more linker nucleotide sequences (i.e. provided between the first, second, third, fourth, fifth and / or sixth nucleotide sequences), the linker sequences are preferably selected such that they do not substantially affect post-transcriptional processing of the polynucleotide when the polynucleotide is a polyribonucleotide. In preferred embodiments, where a polynucleotide according to the present disclosure comprises one more linker sequences, splicing of the polynucleotide when the polynucleotide is a polyribonucleotide is substantially the same as splicing of an equivalent polyribonucleotide lacking the linker nucleotide sequence(s). Similarly, where a polynucleotide according to the present disclosure comprises one more linker nucleotide sequences (i.e. provided between the first, second, third, fourth, fifth and / or sixth nucleotide sequences), the linker sequences are preferably selected such that they do not alter the amino acid sequence of a polypeptide encoded by the polynucleotide. In preferred embodiments, where a polynucleotide according to the present disclosure comprises one more linker sequences, the polynucleotide encodes the same polypeptide as the equivalent polyribonucleotide lacking the linker nucleotide sequence(s). In some embodiments, the polynucleotide further comprises inverted terminal repeat (ITR) sequences. In some embodiments, the polynucleotide comprises an ITR 5’ to the first nucleotide sequence (and 5’ to the P37829 promoter and / or enhancer sequences, when present). In some embodiments, the polynucleotide comprises an ITR 3’ to the nucleotide sequence encoding a polypeptide of interest (and 3’ to the stop codon, polyadenylation signal sequence and / or terminator sequence, when present). In some embodiments, the polynucleotide comprises an ITR sequence at its 5’ end, and an ITR sequences at its 3’ end. In some embodiments, the first nucleotide of the ITR sequence provided at the 5’ end of the polynucleotide is provided within 1 to 25 nucleotides, e.g. within one of 1 to 20, 1 to 15, 1 to 10, or 1 to 5 nucleotides of the first nucleotide of the polynucleotide (i.e. position 1 of the nucleotide sequence of the polynucleotide). In some embodiments, the final nucleotide of the ITR sequence provided at the 3’ end of the polynucleotide is provided within 1 to 25 nucleotides, e.g. within one of 1 to 20, 1 to 15, 1 to 10, or 1 to 5 nucleotides of the final nucleotide of the polynucleotide (i.e. the terminal position of the nucleotide sequence of the polynucleotide). In some embodiments, the polynucleotide of the present disclosure (i.e. comprising the first, second, third, fourth, fifth and / or sixth nucleotide sequences described herein) has a size permitting its delivery as a gene therapy, i.e. in a suitable vector. In some embodiments, the polynucleotide consists of a nucleotide sequence having a size within the packaging limit of a vector for delivering the polynucleotide. In some embodiments, the polynucleotide has a size within the packaging limit of an AAV vector. In some embodiments, the polynucleotide has a size within the packaging limit of an AAV vector of one of the following serotypes: AAV9, AAV9.45, AAV-PHP.B, AAV1, AAV2, AAV2i8, AAV5, AAV6, AAV8, AAV10 or AAVrh74. In some embodiments, the polynucleotide has a size within the packaging limit of an AAV vector of one of the following serotypes: AAV9, AAV9.45, AAV-PHP.B, AAV1, AAV2, AAV2.7m8, AAV2i8, AAV5, AAV6, AAV8, AAV10 or AAVrh74. In some embodiments, the polynucleotide of the present disclosure (i.e. comprising the first, second, third, fourth, fifth and / or sixth nucleotide sequences described herein) consists of fewer than 6,000 nucleotides, e.g. one of ≤5,000, ≤4,750, ≤4,500, ≤4,250, ≤4,000, ≤3,750, ≤3,500, ≤3,250, ≤3,000, ≤2,750, ≤2,500, ≤2,250, ≤2,000, ≤1,750, ≤1,500, ≤1,250 or ≤1,000 nucleotides. In preferred embodiments, the polynucleotide of the present disclosure consists of fewer nucleotides than the number of nucleotides of a known SMN2 exon 6 to exon 8-derived transgene expression system (e.g. an SMN2 exon 6 to exon 8-derived transgene expression system described in Zhang, et al., Gene Ther. (2001) 8: 1532-1538, WO 2022 / 204471 A1, Monteys et al. Nature (2021) 596: 291-295 or WO 2021 / 163556 A1). In some embodiments, the polynucleotide of the present disclosure consists of fewer nucleotides than a polynucleotide comprising: (i) SEQ ID NO:36 and (ii) a nucleotide sequence encoding a polypeptide of interest (i.e. adjacent and 3’ to SEQ ID NO:36, the context of the complete sequence of the polynucleotide). Such polynucleotides are described e.g. in WO 2021 / 163556 A1. P37829 Herein, for conciseness, ‘a polynucleotide comprising: (i) SEQ ID NO:36 and (ii) a nucleotide sequence encoding a polypeptide of interest (i.e. adjacent and 3’ to SEQ ID NO:36, in the context of the complete sequence of the polynucleotide)’ is also referred to herein simply as ‘a SMN2ind minigene polynucleotide’. In some embodiments, the polynucleotide of the present disclosure consists of a number of nucleotides that is less than 1 times, e.g. ≤0.99 times, ≤0.95 times, ≤0.9 times, ≤0.85 times, ≤0.8 times, ≤0.75 times, ≤0.7 times, ≤0.65 times, ≤0.6 times, ≤0.55 times, ≤0.5 times, ≤0.45 times, ≤0.4 times, ≤0.35 times, ≤0.3 times or ≤0.25 times the number of nucleotides of a SMN2ind minigene polynucleotide. In some embodiments, the region of a polynucleotide of the present disclosure formed by the first, second, third, fourth and fifth nucleotide sequences consists of fewer nucleotides than the number of nucleotides in SEQ ID NO:36. In some embodiments, the region of a polynucleotide of the present disclosure formed by the first, second, third, fourth and fifth nucleotide sequences consists of a number of nucleotides that is less than 1 times, e.g. ≤0.99 times, ≤0.95 times, ≤0.9 times, ≤0.85 times, ≤0.8 times, ≤0.75 times, ≤0.7 times, ≤0.65 times, ≤0.6 times, ≤0.55 times, ≤0.5 times, ≤0.45 times, ≤0.4 times, ≤0.35 times, ≤0.3 times or ≤0.25 times the number of nucleotides in SEQ ID NO:36. The polynucleotide of the present disclosure may comprise 5’ cap, 5’ UTR, 3’ UTR and / or PolyA tail nucleotide sequences. In some embodiments, the polynucleotide comprises a 5’ UTR 5’ to (i.e. upstream of, in the context of the nucleotide sequence of the polynucleotide) a start codon. In some embodiments, the polynucleotide comprises a 3’ UTR 3’ to (i.e. downstream of, in the context of the nucleotide sequence of the polynucleotide) a stop codon. In some embodiments, the polynucleotide comprises a 3’ UTR 5’ to a polyadenylation signal sequence. In some embodiments, the polynucleotide comprises a 3’ UTR 3’ to a stop codon and 5’ to a polyadenylation signal sequence. In some embodiments, the polynucleotide of the present disclosure comprises one or more nucleotide sequences encoding a selectable marker, to facilitate identification and / or selection of cells comprising / expressing the polynucleotide. Selectable markers include proteins that confer resistance to antibiotics or other toxins, e.g., blasticidin, ampicillin, neomycin, methotrexate, or tetracycline, and proteins that complement auxotrophic deficiencies. In some embodiments, the polynucleotide of the present disclosure comprises a nucleotide sequence encoding an internal ribosome entry site (IRES). In some embodiments, the polynucleotide comprises a nucleotide sequence permitting two or more polypeptides to be translated separately from a single polyribonucleotide. The polynucleotides of the present disclosure may be provided in purified or isolated form, i.e. from other nucleic acid, or naturally-occurring biological material. P37829 Particular exemplary polynucleotides In some embodiments, a polynucleotide according to the present disclosure comprises: a first nucleotide sequence comprising, or consisting of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to a nucleotide sequence selected from Column A of Table A; a second nucleotide sequence comprising, or consisting of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to a nucleotide sequence selected from Column B of Table A; a third nucleotide sequence comprising, or consisting of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to a nucleotide sequence selected from Column C of Table A; a fourth nucleotide sequence comprising, or consisting of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to a nucleotide sequence selected from Column D of Table A; and a fifth nucleotide sequence comprising, or consisting of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to a nucleotide sequence selected from Column E of Table A. In accordance with the preceding paragraph, in some embodiments the nucleotide sequence selected from Column A of Table A, and the nucleotide sequence selected from Column B of Table A, and the nucleotide sequence selected from Column C of Table A, and the nucleotide sequence selected from Column B of Table A, and the nucleotide sequence selected from Column D of Table A, and the nucleotide sequence selected from Column B of Table A, and the nucleotide sequence selected from Column E of Table A are all selected form the same row of Table A. By way of illustration, in some embodiments the nucleotide sequences selected from Columns A, B, C, D and E of Table A may be selected from row 3 of Table 1, and therefore may be SEQ ID NOs:5, 91418 and 20, respectively. In some embodiments, the polynucleotide comprises: a first nucleotide sequence (i) comprising, or consisting of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to a nucleotide sequence according to SEQ ID NO:1; and comprising ‘GGC’ at the positions corresponding to positions 82 to 84 of SEQ ID NO:2; and (iii) consisting of ≤45 nucleotides; a second nucleotide sequence (i) comprising a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:7 at its 5’ end; and (ii) comprising a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:8 at its 3’ end; and (iii) comprising ‘C’ at the position corresponding to position 5766 of SEQ ID NO:30; and (iv) consisting of fewer than 300 nucleotides; a third nucleotide sequence (i) comprising, or consisting of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) P37829 sequence identity to a nucleotide sequence according to SEQ ID NO:11; and (ii) comprising ‘A’ at the position corresponding to position 2 of SEQ ID NO:12; and (iii) comprising insertion of ‘A’ after the position corresponding to position 48 of SEQ ID NO:12; a fourth nucleotide sequence (i) comprising a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:15 at its 5’ end; and (ii) comprising a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:16 at its 3’ end; and (iii) consisting of fewer than 255 nucleotides; and a fifth nucleotide sequence consisting of the dinucleotide ‘GA’. In some embodiments, the polynucleotide comprises: a first nucleotide sequence comprising, or consisting of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:106; a second nucleotide sequence comprising, or consisting of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:10; a third nucleotide sequence comprising, or consisting of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:13; a fourth nucleotide sequence comprising, or consisting of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:17; and a fifth nucleotide sequence consisting of the dinucleotide ‘GA’. In some embodiments, the polynucleotide comprises a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:22. In some embodiments, the polynucleotide comprises: a first nucleotide sequence comprising, or consisting of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:3; a second nucleotide sequence comprising, or consisting of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:10; a third nucleotide sequence comprising, or consisting of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:13; a fourth nucleotide sequence comprising, or consisting of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:17; and P37829 a fifth nucleotide sequence consisting of the dinucleotide ‘GA’. In some embodiments, the polynucleotide comprises a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:23. In some embodiments, the polynucleotide comprises: a first nucleotide sequence (i) comprising, or consisting of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to a nucleotide sequence according to SEQ ID NO:1; and comprising ‘GGC’ at the positions corresponding to positions 82 to 84 of SEQ ID NO:2; and (iii) comprising ‘CTG’ at the positions corresponding to positions 109 to 111 of SEQ ID NO:2; a second nucleotide sequence (i) comprising a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:7 at its 5’ end; and (ii) comprising a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:8 at its 3’ end; and (iii) comprising ‘C’ at the position corresponding to position 5766 of SEQ ID NO:30; and (iv) consisting of fewer than 500 nucleotides; a third nucleotide sequence (i) comprising, or consisting of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to a nucleotide sequence according to SEQ ID NO:11; and (ii) comprising ‘A’ at the position corresponding to position 2 of SEQ ID NO:12; and (iii) comprising insertion of ‘A’ after the position corresponding to position 48 of SEQ ID NO:12; and (iv) comprising insertion of ‘GCCACC’ after the position corresponding to position 6 of SEQ ID NO:12; and (v) comprising ‘TG’ at the positions corresponding to positions 8 and 9 of SEQ ID NO:12; a fourth nucleotide sequence (i) comprising a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:15 at its 5’ end; and (ii) comprising a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:16 at its 3’ end; and (iii) consisting of fewer than 500 nucleotides; and a fifth nucleotide sequence comprising, or consisting of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:20. In some embodiments, the polynucleotide comprises: a first nucleotide sequence comprising, or consisting of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:5; a second nucleotide sequence comprising, or consisting of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:9; a third nucleotide sequence comprising, or consisting of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:14; a fourth nucleotide sequence comprising, or consisting of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:18; and a fifth nucleotide sequence comprising, or consisting of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:20. In some embodiments, the polynucleotide comprises a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:24. In some embodiments, the polynucleotide comprises: a first nucleotide sequence (i) comprising, or consisting of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to a nucleotide sequence according to SEQ ID NO:1; and comprising ‘GGC’ at the positions corresponding to positions 82 to 84 of SEQ ID NO:2; and (iii) comprising ‘CAG’ at the positions corresponding to positions 109 to 111 of SEQ ID NO:2; a second nucleotide sequence (i) comprising a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:7 at its 5’ end; and (ii) comprising a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:8 at its 3’ end; and (iii) comprising ‘C’ at the position corresponding to position 5766 of SEQ ID NO:30; and (iv) consisting of fewer than 500 nucleotides; a third nucleotide sequence (i) comprising, or consisting of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to a nucleotide sequence according to SEQ ID NO:11; and (ii) comprising ‘A’ at the position corresponding to position 2 of SEQ ID NO:12; and (iii) comprising insertion of ‘A’ after the position corresponding to position 48 of SEQ ID NO:12; a fourth nucleotide sequence (i) comprising a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:15 at its 5’ end; and (ii) comprising a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:16 at its 3’ end; and (iii) consisting of fewer than 500 nucleotides; and a fifth nucleotide sequence comprising, or consisting of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:21. In some embodiments, the polynucleotide comprises: a first nucleotide sequence comprising, or consisting of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:6; a second nucleotide sequence comprising, or consisting of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:9; a third nucleotide sequence comprising, or consisting of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:13; a fourth nucleotide sequence comprising, or consisting of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:18; and a fifth nucleotide sequence comprising, or consisting of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:20. In some embodiments, the polynucleotide comprises a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:25. In some embodiments, the polynucleotide comprises: a first nucleotide sequence (i) comprising, or consisting of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to a nucleotide sequence according to SEQ ID NO:1; and comprising ‘GGC’ at the positions corresponding to positions 82 to 84 of SEQ ID NO:2; and (iii) consisting of ≤45 nucleotides; In some embodiments, the polynucleotide comprises: a second nucleotide sequence (i) comprising a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:7 at its 5’ end; and (ii) comprising a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:8 at its 3’ end; and (iii) comprising ‘C’ at the position corresponding to position 5766 of SEQ ID NO:30; and (iv) consisting of fewer than 300 nucleotides; a third nucleotide sequence (i) comprising, or consisting of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to a nucleotide sequence according to SEQ ID NO:11; and (ii) comprising ‘A’ at the position corresponding to position 2 of SEQ ID NO:12; and (iii) comprising insertion of ‘A’ after the position corresponding to position 48 of SEQ ID NO:12; a fourth nucleotide sequence (i) comprising a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:15 at its 5’ end; and (ii) comprising a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:16 at its 3’ end; and (iii) consisting of fewer than 255 nucleotides; and P37829 a fifth nucleotide sequence consisting of the trinucleotide ‘GAG’. In some embodiments, the polynucleotide comprises: a first nucleotide sequence comprising, or consisting of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:3; a second nucleotide sequence comprising, or consisting of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:10; a third nucleotide sequence comprising, or consisting of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:13; a fourth nucleotide sequence comprising, or consisting of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:17; and a fifth nucleotide sequence consisting of the trinucleotide ‘GAG’. In some embodiments, the polynucleotide comprises a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:28. In some embodiments, the polynucleotide comprises: a first nucleotide sequence (i) comprising, or consisting of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to a nucleotide sequence according to SEQ ID NO:1; and comprising ‘GCC’ at the positions corresponding to positions 82 to 84 of SEQ ID NO:2; and (iii) consisting of ≤45 nucleotides; In some embodiments, the polynucleotide comprises: a second nucleotide sequence (i) comprising a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:7 at its 5’ end; and (ii) comprising a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:8 at its 3’ end; and (iii) comprising ‘C’ at the position corresponding to position 5766 of SEQ ID NO:30; and (iv) consisting of fewer than 300 nucleotides; a third nucleotide sequence (i) comprising, or consisting of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to a nucleotide sequence according to SEQ ID NO:11; and (ii) comprising ‘A’ at the position corresponding to position 2 of SEQ ID NO:12; and (iii) comprising deletion of the position corresponding to position 20 of SEQ ID NO:12; and (iv) comprising insertion of ‘A’ after the position corresponding to position 48 of SEQ ID NO:12; a fourth nucleotide sequence (i) comprising a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:15 at its 5’ end; and (ii) comprising a nucleotide sequence having at least 80% P37829 (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:16 at its 3’ end; and (iii) consisting of fewer than 255 nucleotides; and a fifth nucleotide sequence consisting of the trinucleotide ‘GAG’. In some embodiments, the polynucleotide comprises: a first nucleotide sequence comprising, or consisting of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:3; a second nucleotide sequence comprising, or consisting of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:10; a third nucleotide sequence comprising, or consisting of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:27; a fourth nucleotide sequence comprising, or consisting of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:17; and a fifth nucleotide sequence consisting of the trinucleotide ‘GAG’. In some embodiments, the polynucleotide comprises a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:29. In some embodiments, the polynucleotide does not consist of, or does not comprise, SEQ ID NO:36. In some embodiments, the polynucleotide comprises a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to one of SEQ ID NOs:37 to 105. In some embodiments, the polynucleotide comprises: a first nucleotide sequence (i) comprising, or consisting of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to a nucleotide sequence according to SEQ ID NO:221; and (ii) consisting of ≤45 nucleotides; a second nucleotide sequence (i) comprising a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:7 at its 5’ end; and (ii) comprising a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:8 at its 3’ end; and (iii) comprising ‘C’ at the position corresponding to position 5766 of SEQ ID NO:30; and (iv) consisting of fewer than 300 nucleotides; a third nucleotide sequence (i) comprising, or consisting of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) P37829 sequence identity to a nucleotide sequence according to SEQ ID NO:11; and (ii) comprising ‘A’ at the position corresponding to position 2 of SEQ ID NO:12; and (iii) comprising insertion of ‘A’ after the position corresponding to position 48 of SEQ ID NO:12; a fourth nucleotide sequence (i) comprising a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:15 at its 5’ end; and (ii) comprising a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:16 at its 3’ end; and (iii) consisting of fewer than 255 nucleotides; and a fifth nucleotide sequence consisting of the dinucleotide ‘TG’. In some embodiments, the polynucleotide comprises: a first nucleotide sequence comprising, or consisting of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:219; a second nucleotide sequence comprising, or consisting of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:10; a third nucleotide sequence comprising, or consisting of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:13; a fourth nucleotide sequence comprising, or consisting of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:17; and a fifth nucleotide sequence consisting of the dinucleotide ‘TG’. In some embodiments, the polynucleotide comprises a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:111. In some embodiments, the polynucleotide comprises: a first nucleotide sequence (i) comprising, or consisting of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to a nucleotide sequence according to SEQ ID NO:221; and (ii) consisting of ≤45 nucleotides; a second nucleotide sequence (i) comprising a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:7 at its 5’ end; and (ii) comprising a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:8 at its 3’ end; and (iii) comprising ‘C’ at the position corresponding to position 5766 of SEQ ID NO:30; and (iv) consisting of fewer than 300 nucleotides; P37829 a third nucleotide sequence (i) comprising, or consisting of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to a nucleotide sequence according to SEQ ID NO:225; a fourth nucleotide sequence (i) comprising a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:15 at its 5’ end; and (ii) comprising a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:16 at its 3’ end; and (iii) consisting of fewer than 255 nucleotides; and a fifth nucleotide sequence consisting of the dinucleotide ‘TG’. In some embodiments, the polynucleotide comprises: a first nucleotide sequence comprising, or consisting of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:219; a second nucleotide sequence comprising, or consisting of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:10; a third nucleotide sequence comprising, or consisting of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:223; a fourth nucleotide sequence comprising, or consisting of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:17; and a fifth nucleotide sequence consisting of the dinucleotide ‘TG’. In some embodiments, the polynucleotide comprises a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:116. In some embodiments, the polynucleotide comprises: a first nucleotide sequence (i) comprising, or consisting of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to a nucleotide sequence according to SEQ ID NO:221; and (ii) consisting of ≤45 nucleotides; a second nucleotide sequence (i) comprising a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:7 at its 5’ end; and (ii) comprising a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:8 at its 3’ end; and (iii) comprising ‘C’ at the position corresponding to position 5766 of SEQ ID NO:30; and (iv) consisting of fewer than 300 nucleotides; P37829 a third nucleotide sequence (i) comprising, or consisting of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to a nucleotide sequence according to SEQ ID NO:225; a fourth nucleotide sequence (i) comprising a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:227; and (iii) consisting of fewer than 280 nucleotides; and a fifth nucleotide sequence consisting of the dinucleotide ‘TG’. In some embodiments, the polynucleotide comprises: a first nucleotide sequence comprising, or consisting of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:220; a second nucleotide sequence comprising, or consisting of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:10; a third nucleotide sequence comprising, or consisting of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:224; a fourth nucleotide sequence comprising, or consisting of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:227; and a fifth nucleotide sequence consisting of the dinucleotide ‘TG’. In some embodiments, the polynucleotide comprises a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:164. In some embodiments, the polynucleotide comprises: a first nucleotide sequence (i) comprising, or consisting of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to a nucleotide sequence according to SEQ ID NO:221; and (ii) consisting of ≤45 nucleotides; a second nucleotide sequence (i) comprising, or consisting of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to a nucleotide sequence according to SEQ ID NO:229; a third nucleotide sequence (i) comprising, or consisting of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to a nucleotide sequence according to SEQ ID NO:225; a fourth nucleotide sequence (i) comprising a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:227; and (iii) consisting of fewer than 280 nucleotides; and a fifth nucleotide sequence consisting of the dinucleotide ‘TG’. P37829 In some embodiments, the polynucleotide comprises: a first nucleotide sequence comprising, or consisting of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:220; a second nucleotide sequence comprising, or consisting of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:228; a third nucleotide sequence comprising, or consisting of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:224; a fourth nucleotide sequence comprising, or consisting of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:227; and a fifth nucleotide sequence consisting of the dinucleotide ‘TG’. In some embodiments, the polynucleotide comprises a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:171. In some embodiments, the polynucleotide comprises a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to one of SEQ ID NOs:111 to 200. In some embodiments, the polynucleotide comprises a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to one of SEQ ID NOs:37 to 105, or 111 to 200. Splicing modifiers Aspects and embodiments of the present disclosure pertain to splicing modifiers. Splicing modifiers are molecules that influence splicing of polyribonucleotides. Such molecules are reviewed e.g. in Tang et al., Molecules (2021) 26(8):2263 and Schneider-Poetsch et al., The Journal of Antibiotics (2021) 74:603-616, both of which are hereby incorporated by reference in their entirety. Splicing modifiers generally reduce / prevent association of factors required for normal post-transcriptional processing (e.g. components of the spliceosome) with RNA. Splicing modifiers typically bind to a nucleotide sequence of a polyribonucleotide and either inhibit or promote the association of RNA-binding proteins and / or non-coding RNAs which function as splicing activators or repressors. Through competitive inhibition of the recruitment of splicing activators and splicing repressors to the polyribonucleotide, splicing modifiers can alter the equilibrium of the splicing-regulatory RNA structures, and thus promote an increase or decrease in skipping or inclusion of an exon and / or retention or excision of an intron in the mature RNA molecule produced by splicing. P37829 In some embodiments, a splicing modifier is a small molecule or a splice-switching nucleic acid (e.g. a splice-switching oligonucleotide). A ‘small molecule’ refers to a low molecular weight (<1000 daltons, typically about 300 to about 700 daltons) organic compound. Splice-switching nucleic acids are reviewed e.g. in Haves and Hastings, Nucleic Acids Res. (2016) 44(14): 6549–6563, which is hereby incorporated by reference in its entirety. Splice-switching nucleic acids include e.g. splice-switching oligonucleotides (SSOs). They disrupt the normal splicing of target RNA transcripts by blocking the RNA:RNA base-pairing and / or protein:RNA binding interactions that occur between components of the splicing machinery and pre-mRNA. Splice-switching nucleic acids may be designed to target a specific region of the target transcript, e.g. to promote skipping of exon(s) of interest and / or to promote inclusion of exon(s) of interest and / or to promote retention of introns of interest and / or to promote excision of introns of interest. SSOs often comprise alterations to oligonucleotide sugar-phosphate backbones in order to reduce / prevent RNAseh degradation, such as e.g. phosphorothioate linkages, phosphorodiamidate linkages such as phosphorodiamidate morpholino (PMOs), and may comprise e.g. peptide nucleic acids (PNAs), locked nucleic acids (LNAs), methoxyethyl nucleotide modifications, e.g.2′O-methyl (2′OMe) and 2′-O-methoxyethyl (MOE) ribose modifications and / or 5’-methylcytosine modifications. Small molecule splicing modifiers contemplated in accordance with the present disclosure include RG- 7800 and RG-7916 (also known as risdiplam), and analogs thereof. RG-7800 and RG-7916 bind to the 5’ splice site of intron 7 and exonic splicing enhancer 2 of exon 7 of human SMN2, thereby stabilising the transient double-strand RNA structure formed by the SMN2 pre-mRNA and U1 snRNP complex, and promoting inclusion of exon 7 in the mature RNA molecule obtained following splicing of pre-mRNA transcribed from SMN2. RG-7800 and RG-7916 are useful to restore functional SMN2 protein expression from SMN2 alleles comprising the spinal muscular atrophy (SMA)-associated polymorphism c.840C>T (which potentiates skipping of exon 7). RG-7916 (DrugBank Acc. No. DB15305) is a close structural analog of RG-7800 having improved potency, pharmacokinetics and safety profile than RG-7800, and is approved by the FDA for the treatment of SMA. Further analogs of RG-7800 and RG-7916 having similar splicing modifier activity include SMN-C2, SMN-C3, SMN-C5 and TEC-1. Branaplam (DrugBank Acc. No. DB14918; also known as LMI-070) is another small molecule splicing modifier that promotes inclusion of exon 7 in the mature RNA expressed from SMN2. Like RG-7800 and RG-7916, branaplam binds to the 5’ splice site of intron 7 of human SMN2. PK4C9 (also known as homocarbonyltopsentin) is another small molecule splicing modifier that promotes inclusion of exon 7 in the mature RNA expressed from SMN2. It is thought to bind to the 5’ splice site of exon 7 and TSL2, and improve accessibility of the 5′ splice site via stabilising a triloop structure of TSL2. Small molecule splicing modifiers that promote inclusion of exon 7 in the mature RNA expressed from SMN2 are described e.g. in WO 2015 / 173181 A1 and WO 2009 / 151546 A2, which are hereby P37829 incorporated by reference in their entirety. Further small molecule splicing modifiers that promote inclusion of exon 7 in the mature RNA expressed from SMN2 are described e.g. in WO 2022 / 204471 A1, which is hereby incorporated by reference in its entirety. Nusinersen (DrugBank Acc. No. DB13161) is a splice-switching oligonucleotide that promotes exon 7 retention in mature RNA expressed from human SMN2. Nusinersen is an 18-mer 2’-MOe phosphorothioate antisense oligonucleotide that hybridises to intronic splicing silencer site 1 of intron 7, occupying the site and thereby inhibiting the association of the splicing suppressor ribonucleoproteins hnRNPs A1 / A2, thus promoting inclusion of exon 7 in the mature RNA molecule. The splicing modifier according to the present disclosure preferably promotes inclusion of SMN2 exon 7 in RNA obtained following splicing of pre-mRNA transcribed from human SMN2. Such molecules increase the proportion of RNA molecules comprising SMN2 exon 7 among RNA molecules obtained following splicing of pre-mRNA transcribed from human SMN2 (i.e. relative to the proportion obtained in the absence of the splicing modifier). For conciseness, ‘a splicing modifier that promotes inclusion of SMN2 exon 7 in RNA obtained following splicing of pre-mRNA transcribed from human SMN2’ may be referred to herein simply as ‘a splicing modifier that promotes SMN2 exon 7 inclusion’ In some embodiments, the splicing modifier promotes inclusion of exon 7 in RNA obtained following splicing of pre-mRNA transcribed from an allele of human SMN2 comprising c.840C>T. That is, in some embodiments, the splicing modifier increases the proportion of RNA molecules comprising SMN2 exon 7 among RNA molecules obtained following splicing of pre-mRNA transcribed from an allele of human SMN2 comprising c.840C>T (i.e. relative to the proportion obtained in the absence of the splicing modifier). In some embodiments, the splicing modifier increases the level of human SMN2 protein comprising amino acids encoded by exon 7 of human SMN2 (i.e. relative to the level detected in the absence of the splicing modifier). In some embodiments, the splicing modifier increases the proportion of polypeptides comprising amino acids encoded by exon 7 of human SMN2 among polypeptides expressed from human SMN2 (i.e. relative to the proportion obtained in the absence of the splicing modifier). In some embodiments, the splicing modifier increases the proportion of polypeptides comprising amino acids encoded by exon 7 of human SMN2 among polypeptides expressed from an allele of human SMN2 comprising c.840C>T (i.e. relative to the proportion obtained in the absence of the splicing modifier). In some embodiments, the splicing modifier promotes inclusion of the third nucleotide sequence in the product of splicing of a polynucleotide according to the present disclosure (i.e. where the polynucleotide is a polyribonucleotide). In some embodiments, the splicing modifier increases the proportion of molecules comprising the third nucleotide sequence among molecules obtained following splicing of a polynucleotide according to the present disclosure (i.e. where the polynucleotide is a polyribonucleotide). In some embodiments, the splicing modifier promotes inclusion of the nucleotide sequence consisting of SEQ ID NO:13 in molecules obtained following splicing of a polyribonucleotide consisting of the sequence P37829 of SEQ ID NO:22. In some embodiments, the splicing modifier increases the proportion of molecules comprising the nucleotide sequence consisting of SEQ ID NO:13 among molecules obtained following splicing of a polyribonucleotide consisting of the sequence of SEQ ID NO:22. In some embodiments, the splicing modifier promotes inclusion of the nucleotide sequence consisting of SEQ ID NO:13 in molecules obtained following splicing of a polyribonucleotide consisting of the sequence of SEQ ID NO:23. In some embodiments, the splicing modifier increases the proportion of molecules comprising the nucleotide sequence consisting of SEQ ID NO:13 among molecules obtained following splicing of a polyribonucleotide consisting of the sequence of SEQ ID NO:23. In some embodiments, the splicing modifier promotes inclusion of the nucleotide sequence consisting of SEQ ID NO:14 in molecules obtained following splicing of a polyribonucleotide consisting of the sequence of SEQ ID NO:24. In some embodiments, the splicing modifier increases the proportion of molecules comprising the nucleotide sequence consisting of SEQ ID NO:14 among molecules obtained following splicing of a polyribonucleotide consisting of the sequence of SEQ ID NO:24. In some embodiments, the splicing modifier promotes inclusion of the nucleotide sequence consisting of SEQ ID NO:13 in molecules obtained following splicing of a polyribonucleotide consisting of the sequence of SEQ ID NO:25. In some embodiments, the splicing modifier increases the proportion of molecules comprising the nucleotide sequence consisting of SEQ ID NO:13 among molecules obtained following splicing of a polyribonucleotide consisting of the sequence of SEQ ID NO:25. In some embodiments, the splicing modifier promotes inclusion of the nucleotide sequence consisting of SEQ ID NO:13 in molecules obtained following splicing of a polyribonucleotide consisting of the sequence of SEQ ID NO:28. In some embodiments, the splicing modifier increases the proportion of molecules comprising the nucleotide sequence consisting of SEQ ID NO:13 among molecules obtained following splicing of a polyribonucleotide consisting of the sequence of SEQ ID NO:28. In some embodiments, the splicing modifier promotes inclusion of the nucleotide sequence consisting of SEQ ID NO:27 in molecules obtained following splicing of a polyribonucleotide consisting of the sequence of SEQ ID NO:29. In some embodiments, the splicing modifier increases the proportion of molecules comprising the nucleotide sequence consisting of SEQ ID NO:27 among molecules obtained following splicing of a polyribonucleotide consisting of the sequence of SEQ ID NO:29. Splicing modifiers having such functional properties can be identified by analysis e.g. in suitable in vitro assays. Such assays may comprise culturing cells in vitro in the presence or absence of a candidate splicing modifier, and analysing the RNA and / or protein produced after an appropriate period of time for an effect of the candidate splicing modifier to be observed. By way of illustration, cells can be transfected with a vector comprising DNA having the sequence of SEQ ID NO:22 and cultured in the presence or absence of a candidate splicing modifier for a suitable period of time (e.g.24, 48, 72 hours). RNA can subsequently be isolated from the cells, and analysed (e.g. by qRT-PCR) to determine the P37829 level / proportion of mature RNA molecules comprising the nucleotide sequence consisting of SEQ ID NO:13. In some embodiments, a splicing modifier that promotes SMN2 exon 7 inclusion according to the present disclosure is a compound of formula (I) of WO 2015 / 173181 A1. In some embodiments, a splicing modifier that promotes SMN2 exon 7 inclusion according to the present disclosure is a compound selected from those listed in claim 39 of WO 2015 / 173181 A1. In some embodiments, a splicing modifier that promotes SMN2 exon 7 inclusion according to the present disclosure is a compound selected from those listed in claim 40 of WO 2015 / 173181 A1. In some embodiments, the splicing modifier according to the present disclosure is selected from: RG- 7916, RG-7800, SMN-C2, SMN-C3, SMN-C5, TEC-1, branaplam, PK4C9 and nusinersen. In some embodiments, the splicing modifier is selected from: RG-7916, RG-7800, SMN-C2, SMN-C3, SMN-C5 and TEC-1. In some embodiments, the splicing modifier is selected from RG-7916 and RG-7800. In preferred embodiments, the splicing modifier is risdiplam (RG-7916). Functional properties of the polynucleotides In aspects and embodiments of the present disclosure, the polynucleotides of the present disclosure may be characterised by reference to one or more functional properties. In some embodiments, where the polynucleotide is a polyribonucleotide, splicing of the polyribonucleotide in the absence of a splicing modifier that promotes SMN2 exon 7 inclusion yields polyribonucleotides substantially lacking the third nucleotide sequence. In some embodiments, where the polynucleotide is a polyribonucleotide, splicing of the polyribonucleotide in the presence of a splicing modifier that promotes SMN2 exon 7 inclusion yields polyribonucleotides comprising the third nucleotide sequence. In some embodiments, in the presence of a splicing modifier that promotes SMN2 exon 7 inclusion, inclusion of the third nucleotide sequence is promoted in splicing of the polyribonucleotide, favouring the production of mature RNA molecules encoding the polypeptide of interest, and thus expression of the polypeptide of interest at the protein level. Such polynucleotides may be referred to herein as ‘ON-switch’ polynucleotides. In some embodiments, cells comprising an ON-switch polynucleotide of the present disclosure substantially do not express the polypeptide of interest in the absence of a splicing modifier that promotes SMN2 exon 7 inclusion. In some embodiments, cells comprising the ON-switch polynucleotide express the polypeptide of interest in the presence of a splicing modifier that promotes SMN2 exon 7 inclusion. Exemplary ON-switch polynucleotides according to the present disclosure include polynucleotides comprising SEQ ID NO:22, 23, 24 or 25. Further exemplary ON-switch polynucleotides according to the present disclosure include polynucleotides comprising one of SEQ ID NOs:37 to 105. P37829 Inclusion of the third nucleotide sequence as described herein in the products of splicing of a polyribonucleotide according to the present disclosure can be evaluated using methods that are well known to the person skilled in the art. Such methods include qRT-PCR based methods for the detection and / or quantification of RNA molecules comprising nucleotide sequences of interest. For example, cells may be transduced in vitro with a vector comprising a polynucleotide according to the present disclosure and subsequently cultured in vitro in the presence or absence of a splicing modifier that promotes SMN2 exon 7 inclusion for a period of time appropriate for an effect on splicing of a polyribonucleotide according to the present disclosure to be observed. After such period of time, total RNA may be isolated from the cells, cDNA may be prepared from the total RNA, and the number / proportion of mature RNA molecules comprising the third nucleotide sequence may be evaluated by qPCR using oligonucleotides providing for the specific amplification and / or detection of the products of splicing of the polyribonucleotide (e.g. oligonucleotides hybridising to nucleotide sequences spanning exon:exon boundaries). The qPCR analysis may employ oligonucleotides enabling distinction between RNA molecules comprising the third nucleotide sequence, and RNA molecules lacking the third nucleotide sequence. Such qRT-PCR-based methods for analysing the products of splicing of a polyribonucleotide are described in the experimental examples of the present disclosure. Expression of a polypeptide of interest can be evaluated using any suitable technique for the detection and / or quantification of the relevant polypeptide. Such techniques include e.g. antibody-based methods, (for example flow cytometry, immunocytochemistry, western blot, ELISA), fluorescence microscopy and flow cytometry. In some embodiments, expression of a polypeptide of interest can be evaluated as described in the experimental examples of the present disclosure. In preferred embodiments, expression of a polypeptide of interest may be evaluated by flow cytometry. Herein, within a plurality / population of polyribonucleotides obtained after splicing that ‘substantially lack’ the third nucleotide sequence, the third nucleotide sequence may be present in fewer than 15%, e.g. one of ≤10%, ≤5%, ≤4%, ≤3%, ≤2% or ≤1% of the polyribonucleotides. Conversely, within a plurality / population of polyribonucleotides obtained after splicing that ‘comprise’ the third nucleotide sequence, the third nucleotide sequence may be present in more than 80%, e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100% of the polyribonucleotides. Herein, within a plurality / population of cells that ‘substantially do not express’ a polypeptide of interest, the polypeptide may be expressed by fewer than 15%, e.g. one of ≤10%, ≤5%, ≤4%, ≤3%, ≤2% or ≤1% of the cells. Conversely, within a plurality / population of cells that ‘express’ a polypeptide of interest, the polypeptide may be expressed by more than 80%, e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100% of the cells. In some embodiments, cells that ‘substantially do not express’ a polypeptide of interest may display a level of expression of the polypeptide of interest which is less than 0.2 times, e.g. one of ≤0.1 times, ≤0.09 times, ≤0.08 times, ≤0.07 times, ≤0.06 times, ≤0.05 times, ≤0.04 times, ≤0.03 times, ≤0.02 times, or ≤0.01 times the level of expression by cells that express the polypeptide of interest. In some P37829 embodiments, cells that ‘express’ a polypeptide of interest may display a level of expression of the polypeptide of interest which is greater than 5 times, e.g. one of ≥10 times, ≥20 times, ≥50 times, ≥100 times, ≥1000 times, ≥5000 times or ≥10000 times level of expression by cells that ‘substantially do not express’ the polypeptide of interest. In some embodiments, the level of RNA comprising a nucleotide sequence having at least 80% sequence identity to a nucleotide sequence according to SEQ ID NO:11 in cells comprising a polynucleotide according to the present disclosure following culture in the presence of a splicing modifier that promotes SMN2 exon 7 inclusion is greater than 1 times, e.g. one of ≥2 times, ≥3 times, ≥4 times, ≥5 times, ≥10 times, ≥20 times, ≥50 times, ≥100 times, ≥1000 times, ≥5000 times or ≥10000 times the level in equivalent cells cultured in the absence of the splicing modifier that promotes SMN2 exon 7 inclusion. In some embodiments, the level of RNA comprising a nucleotide sequence having at least 80% sequence identity to a nucleotide sequence according to SEQ ID NO:11 in cells comprising a polynucleotide according to the present disclosure following culture in the absence of a splicing modifier that promotes SMN2 exon 7 inclusion is less than 100 times, e.g. one of ≤50 times, ≤20 times, ≤10 times, ≤5 times, ≤4 times, ≤3 times, ≤2 times or ≤1 times the level of RNA comprising a nucleotide sequence having at least 80% sequence identity to a nucleotide sequence according to SEQ ID NO:11 in equivalent cells not comprising the polynucleotide. In some embodiments, the level of a polypeptide of interest in cells comprising a polynucleotide according to the present disclosure (e.g. an ON-switch polynucleotide) in the presence of a splicing modifier that promotes SMN2 exon 7 inclusion is greater than 1 times, e.g. one of ≥2 times, ≥3 times, ≥4 times, ≥5 times, ≥10 times, ≥20 times, ≥50 times, ≥100 times, ≥1000 times, ≥5000 times or ≥10000 times the level in equivalent cells cultured in the absence of the splicing modifier that promotes SMN2 exon 7 inclusion. In some embodiments, the level of expression of a polypeptide of interest by cells comprising a polynucleotide according to the present disclosure (e.g. an ON-switch polynucleotide) in the absence of a splicing modifier that promotes SMN2 exon 7 inclusion is less than 100 times, e.g. one of ≤50 times, ≤20 times, ≤10 times, ≤5 times, ≤4 times, ≤3 times, ≤2 times or ≤1 times the level of the polypeptide of interest in equivalent cells not comprising the polynucleotide. In some embodiments, the proportion of cells expressing a polypeptide of interest within a population of cells comprising a polynucleotide according to the present disclosure (e.g. an ON-switch polynucleotide) cultured in the presence of a splicing modifier that promotes SMN2 exon 7 inclusion is greater than 1 times, e.g. one of ≥2 times, ≥3 times, ≥4 times, ≥5 times, ≥10 times, ≥20 times, ≥50 times, ≥100 times, ≥1000 times, ≥5000 times or ≥10000 times the proportion of such cells expressing the polypeptide of interest cultured in the absence of the splicing modifier that promotes SMN2 exon 7 inclusion. In some embodiments, the proportion of cells expressing a polypeptide of interest within a population of cells comprising a polynucleotide according to the present disclosure (e.g. an ON-switch polynucleotide) cultured in the absence of a splicing modifier that promotes SMN2 exon 7 inclusion is less than 100 P37829 times, e.g. one of ≤50 times, ≤20 times, ≤10 times, ≤5 times, ≤4 times, ≤3 times, ≤2 times or ≤1 times the proportion of such cells expressing the polypeptide of interest cultured in the presence of the splicing modifier that promotes SMN2 exon 7 inclusion. In some embodiments, in the presence of a splicing modifier that promotes SMN2 exon 7 inclusion, inclusion of the third nucleotide sequence is promoted in splicing of the polyribonucleotide, favouring the production of mature RNA molecules encoding a premature stop codon, and thus preventing expression of the polypeptide of interest at the protein level. Such polynucleotides may be referred to herein as ‘OFF- switch’ polynucleotides. In some embodiments, cells comprising an OFF-switch polynucleotide of the present disclosure express the polypeptide of interest in the absence of a splicing modifier that promotes SMN2 exon 7 inclusion. In some embodiments, cells comprising the OFF-switch polynucleotide do not express the polypeptide of interest in the presence of a splicing modifier that promotes SMN2 exon 7 inclusion. Exemplary OFF-switch polynucleotides according to the present disclosure include polynucleotides comprising SEQ ID NO:28 or 29. In some embodiments, the level of RNA comprising a nucleotide sequence having at least 80% sequence identity to a nucleotide sequence according to SEQ ID NO:26 in cells comprising a polynucleotide according to the present disclosure following culture in the presence of a splicing modifier that promotes SMN2 exon 7 inclusion is greater than 1 times, e.g. one of ≥2 times, ≥3 times, ≥4 times, ≥5 times, ≥10 times, ≥20 times, ≥50 times, ≥100 times, ≥1000 times, ≥5000 times or ≥10000 times the level in equivalent cells cultured in the absence of the splicing modifier that promotes SMN2 exon 7 inclusion. In some embodiments, the level of RNA comprising a nucleotide sequence having at least 80% sequence identity to a nucleotide sequence according to SEQ ID NO:26 in cells comprising a polynucleotide according to the present disclosure following culture in the absence of a splicing modifier that promotes SMN2 exon 7 inclusion is less than 100 times, e.g. one of ≤50 times, ≤20 times, ≤10 times, ≤5 times, ≤4 times, ≤3 times, ≤2 times or ≤1 times the level of the polypeptide of interest in equivalent cells not comprising the polynucleotide. In some embodiments, the level of a polypeptide of interest in cells comprising a polynucleotide according to the present disclosure (e.g. an OFF-switch polynucleotide) in the absence of a splicing modifier that promotes SMN2 exon 7 inclusion is greater than 1 times, e.g. one of ≥2 times, ≥3 times, ≥4 times, ≥5 times, ≥10 times, ≥20 times, ≥50 times, ≥100 times, ≥1000 times, ≥5000 times or ≥10000 times the level in equivalent cells cultured in the presence of the splicing modifier that promotes SMN2 exon 7 inclusion. In some embodiments, the level of expression of a polypeptide of interest by cells comprising a polynucleotide according to the present disclosure (e.g. an OFF-switch polynucleotide) in the presence of a splicing modifier that promotes SMN2 exon 7 inclusion is less than 100 times, e.g. one of ≤50 times, P37829 ≤20 times, ≤10 times, ≤5 times, ≤4 times, ≤3 times, ≤2 times or ≤1 times the level of the polypeptide of interest in equivalent cells not comprising the polynucleotide. In some embodiments, the proportion of cells expressing a polypeptide of interest within a population of cells comprising a polynucleotide according to the present disclosure (e.g. an OFF-switch polynucleotide) cultured in the absence of a splicing modifier that promotes SMN2 exon 7 inclusion is greater than 1 times, e.g. one of ≥2 times, ≥3 times, ≥4 times, ≥5 times, ≥10 times, ≥20 times, ≥50 times, ≥100 times, ≥1000 times, ≥5000 times or ≥10000 times the proportion of such cells expressing the polypeptide of interest cultured in the presence of the splicing modifier that promotes SMN2 exon 7 inclusion. In some embodiments, the proportion of cells expressing a polypeptide of interest within a population of cells comprising a polynucleotide according to the present disclosure (e.g. an OFF-switch polynucleotide) cultured in the presence of a splicing modifier that promotes SMN2 exon 7 inclusion is less than 100 times, e.g. one of ≤50 times, ≤20 times, ≤10 times, ≤5 times, ≤4 times, ≤3 times, ≤2 times or ≤1 times the proportion of such cells expressing the polypeptide of interest cultured in the absence of the splicing modifier that promotes SMN2 exon 7 inclusion. The polynucleotides of the present disclosure possess novel and / or improved properties relative to known transgene expression systems, e.g. known transgene expression systems comprising a SMSM-mediated switch derived from SMN2 exons 6 to 8 (e.g. SMN2 exon 6 to exon 8-derived transgene expression systems described in Zhang, et al., Gene Ther. (2001) 8: 1532-1538, WO 2022 / 204471 A1, Monteys et al. Nature (2021) 596: 291-295 or WO 2021 / 163556 A1). In some embodiments, the polynucleotides of the present disclosure possess novel and / or improved properties relative to a SMN2ind minigene polynucleotide (which is defined hereinabove). In some embodiments, cells comprising a polynucleotide of the present disclosure cultured in the presence of a splicing modifier that promotes SMN2 exon 7 inclusion produce a population of RNA molecules having an increased proportion of RNA molecules comprising a nucleotide sequence having at least 80% sequence identity to a nucleotide sequence according to SEQ ID NO:11 or 26, compared to the population of RNA molecules produced by cells comprising a SMN2ind minigene polynucleotide and cultured under the same conditions. That is, in some embodiments the polynucleotide of the present disclosure is more effective at promoting inclusion of a nucleotide sequence having at least 80% sequence identity to a nucleotide sequence according to SEQ ID NO:11 or 26 in the presence of a splicing modifier that promotes SMN2 exon 7 inclusion, compared to a SMN2ind minigene polynucleotide. That is, the polynucleotides of the present disclosure are more responsive to induction of SMN2 exon 7 variant inclusion in the products of splicing in response to a splicing modifier that promotes SMN2 exon 7 inclusion than SMN2ind minigene polynucleotides. In some embodiments, the proportion of RNA molecules comprising a nucleotide sequence having at least 80% sequence identity to a nucleotide sequence according to SEQ ID NO:11 or 26 among RNA molecules obtained from cells comprising a polynucleotide of the present disclosure cultured in the P37829 presence of a splicing modifier that promotes SMN2 exon 7 inclusion is greater than 1 times, e.g. one of ≥1.01 times, ≥1.02 times, ≥1.03 times, ≥1.04 times, ≥1.05 times, ≥1.1 times, ≥1.2 times, ≥1.3 times, ≥1.4 times, ≥1.5 times, ≥1.6 times, ≥1.7 times, ≥1.8 times, ≥1.9 times, ≥2 times, ≥3 times, ≥4 times, ≥5 times, ≥6 times, ≥7 times, ≥8 times, ≥9 times or ≥10 times the proportion of RNA molecules comprising a nucleotide sequence having at least 80% sequence identity to a nucleotide sequence according to SEQ ID NO:11 or 26 among RNA molecules obtained from cells comprising a SMN2ind minigene polynucleotide and cultured under the same conditions. It will be appreciated that the functional properties described herein are evaluated employing the same experimental conditions for the evaluation of cells comprising the different polynucleotides (i.e. the polynucleotide of the present disclosure, and the SMN2ind minigene polynucleotide). For example, the same cell type, the same splicing modifier that promotes SMN2 exon 7 inclusion, the same concentration of the splicing modifier that promotes SMN2 exon 7 inclusion, etc. are used, the same culture period is provided, and the cells are analysed in order to determine the proportion of RNA molecules comprising the relevant nucleotide sequence and / or the level of the polypeptide of interest in the same way. In some embodiments, cells comprising a polynucleotide of the present disclosure cultured in the absence of a splicing modifier that promotes SMN2 exon 7 inclusion produce a population of RNA molecules having a decreased proportion of RNA molecules comprising a nucleotide sequence having at least 80% sequence identity to a nucleotide sequence according to SEQ ID NO:11 or 26, compared to the population of RNA molecules produced by cells comprising a SMN2ind minigene polynucleotide and cultured under the same conditions. That is, in some embodiments the polynucleotide of the present disclosure is more effective at excluding a nucleotide sequence having at least 80% sequence identity to a nucleotide sequence according to SEQ ID NO:11 or 26 in the absence of a splicing modifier that promotes SMN2 exon 7 inclusion, compared to a SMN2ind minigene polynucleotide. That is, the polynucleotides of the present disclosure are less ‘leaky’ with respect to SMN2 exon 7 variant inclusion in the products of splicing in the absence of a splicing modifier that promotes SMN2 exon 7 inclusion, compared to SMN2ind minigene polynucleotides. Leaky production of mature RNA molecules comprising an SMN2 exon 7 variant (i.e. in the absence of a splicing modifier that promotes SMN2 exon 7 inclusion) may also be referred to herein as ‘background’ production of such RNA molecules. In some embodiments, the proportion of RNA molecules comprising a nucleotide sequence having at least 80% sequence identity to a nucleotide sequence according to SEQ ID NO:11 or 26 among RNA molecules obtained from cells comprising a polynucleotide of the present disclosure cultured in the absence of a splicing modifier that promotes SMN2 exon 7 inclusion is less than 1 times, e.g. ≤0.99 times, ≤0.95 times, ≤0.9 times, ≤0.85 times, ≤0.8 times, ≤0.75 times, ≤0.7 times, ≤0.65 times, ≤0.6 times, ≤0.55 times, ≤0.5 times, ≤0.45 times, ≤0.4 times, ≤0.35 times, ≤0.3 times, ≤0.25 times, ≤0.2 times, ≤0.15 times, ≤0.1 times, ≤0.05 times, or ≤0.01 times the proportion of RNA molecules comprising a nucleotide sequence having at least 80% sequence identity to a nucleotide sequence according to SEQ ID NO:11 or P37829 26 among RNA molecules obtained from cells comprising a SMN2ind minigene polynucleotide and cultured under the same conditions. In some embodiments, cells comprising a polynucleotide of the present disclosure (e.g. an ON-switch polynucleotide) cultured in the presence of a splicing modifier that promotes SMN2 exon 7 inclusion display an increased level of protein expression of the polypeptide of interest, compared to the level of protein expression of the polypeptide of interest by cells comprising a SMN2ind minigene polynucleotide and cultured under the same conditions. That is, in some embodiments the polynucleotide of the present disclosure is more effective at promoting protein expression of the polypeptide of interest in the presence of a splicing modifier that promotes SMN2 exon 7 inclusion, compared to a SMN2ind minigene polynucleotide. That is, the polynucleotides of the present disclosure are more responsive to induction of expression of the polypeptide of interest in the presence of a splicing modifier that promotes SMN2 exon 7 inclusion, compared to SMN2ind minigene polynucleotides. It will be appreciated that for the purposes of such comparison, the different polynucleotides (i.e. the polynucleotide of the present disclosure, and the SMN2ind minigene polynucleotide) preferably encode the same polypeptide of interest. In some embodiments, the level of protein expression of the polypeptide of interest from cells comprising a polynucleotide of the present disclosure (e.g. an ON-switch polynucleotide) cultured in the presence of a splicing modifier that promotes SMN2 exon 7 inclusion is greater than 1 times, e.g. one of ≥1.01 times, ≥1.02 times, ≥1.03 times, ≥1.04 times, ≥1.05 times, ≥1.1 times, ≥1.2 times, ≥1.3 times, ≥1.4 times, ≥1.5 times, ≥1.6 times, ≥1.7 times, ≥1.8 times, ≥1.9 times, ≥2 times, ≥3 times, ≥4 times, ≥5 times, ≥6 times, ≥7 times, ≥8 times, ≥9 times or ≥10 times the level of protein expression of the polypeptide of interest from cells comprising a SMN2ind minigene polynucleotide and cultured under the same conditions. In some embodiments, cells comprising a polynucleotide of the present disclosure (e.g. an ON-switch polynucleotide) cultured in the absence of a splicing modifier that promotes SMN2 exon 7 inclusion display a decreased level of protein expression of the polypeptide of interest, compared to the level of protein expression of the polypeptide of interest by cells comprising a SMN2ind minigene polynucleotide and cultured under the same conditions. That is, in some embodiments the polynucleotide of the present disclosure is more effective at preventing protein expression of the polypeptide of interest in the absence of a splicing modifier that promotes SMN2 exon 7 inclusion, compared to a SMN2ind minigene polynucleotide. That is, the polynucleotides of the present disclosure are less ‘leaky’ with respect to expression of the polypeptide of interest in the absence of a splicing modifier that promotes SMN2 exon 7 inclusion, compared to SMN2ind minigene polynucleotides. Leaky expression of the polypeptide of interest (i.e. in the absence of a splicing modifier that promotes SMN2 exon 7 inclusion) may also be referred to herein as ‘background’ expression of the polypeptide. In some embodiments, the level of protein expression of the polypeptide of interest from cells comprising a polynucleotide of the present disclosure (e.g. an ON-switch polynucleotide) cultured in the absence of a splicing modifier that promotes SMN2 exon 7 inclusion is less than 1 times, e.g. ≤0.99 times, ≤0.95 times, P37829 ≤0.9 times, ≤0.85 times, ≤0.8 times, ≤0.75 times, ≤0.7 times, ≤0.65 times, ≤0.6 times, ≤0.55 times, ≤0.5 times, ≤0.45 times, ≤0.4 times, ≤0.35 times, ≤0.3 times, ≤0.25 times, ≤0.2 times, ≤0.15 times, ≤0.1 times, ≤0.05 times, or ≤0.01 times the level of protein expression of the polypeptide of interest from cells comprising a SMN2ind minigene polynucleotide and cultured under the same conditions. In some embodiments, a polypeptide of interest expressed from a polynucleotide of the present disclosure comprises fewer extraneous additional amino acids (i.e. amino acids additional to the amino acid sequence of the polypeptide of interest) compared to a polypeptide of interest expressed from SMN2ind minigene polynucleotide. In some embodiments, a polypeptide of interest expressed from a polynucleotide of the present disclosure comprises a smaller N-terminal tag (i.e. formed of extraneous, additional amino acids in addition to the amino acid sequence of the polypeptide of interest) than a polypeptide of interest expressed from SMN2ind minigene polynucleotide. That is, in some embodiments, the polynucleotides of the present disclosure provide for the inducible expression of polypeptides of interest comprising fewer extraneous additional amino acids, relative to polypeptides of interest expressed from SMN2ind minigene polynucleotide. Vectors The present disclosure provides vectors comprising the polynucleotides according to the present disclosure. It will be appreciated that a vector is also a polynucleotide, and so in some embodiments a polynucleotide according to the present disclosure may be a vector. A ‘vector’ as used herein refers to a polynucleotide used as a vehicle to transfer exogenous nucleic acid into a cell. The vector may be a vector for expression of the nucleic acid in the cell (i.e. the vector may be an expression vector). Such vectors may include a promoter sequence operably linked to the nucleotide sequence to be expressed. Vectors may also include a termination codon and expression enhancers. Any suitable vectors, promoters, enhancers and termination codons known in the art may be used in a vector according to the present disclosure. The term ‘operably linked’ may include the situation where nucleic acid encoding a polypeptide of interest according to the present disclosure and regulatory nucleic acid sequence(s) (e.g. a promoter and / or enhancers) are covalently linked in such a way as to place the expression of the nucleic acid encoding a polypeptide under the influence or control of the regulatory nucleic acid sequence(s) (thereby forming an expression cassette). Thus, a regulatory sequence is operably linked to the selected nucleic acid sequence if the regulatory sequence is capable of effecting transcription of the nucleic acid sequence. The resulting transcript(s) may then be translated into the desired polypeptide(s). Vectors contemplated in connection with the present disclosure include DNA vectors, RNA vectors, plasmids (e.g. conjugative plasmids (e.g. F plasmids), non-conjugative plasmids, R plasmids, col plasmids, episomes), viral vectors (e.g. retroviral vectors, e.g. gammaretroviral vectors (e.g. murine Leukemia virus (MLV)-derived vectors, e.g. SFG vector), lentiviral vectors, adenovirus vectors, adeno- associated virus vectors, vaccinia virus vectors, baculoviral vectors and herpesvirus vectors), transposon- based vectors, and artificial chromosomes (e.g. yeast artificial chromosomes), e.g. as described in Maus P37829 et al., Annu Rev Immunol (2014) 32:189-225 and Morgan and Boyerinas, Biomedicines (2016) 4:9, which are both hereby incorporated by reference in their entirety. In some embodiments, the vector may be a eukaryotic vector, i.e. a vector comprising the elements necessary for expression of protein from the vector in a eukaryotic cell. In some embodiments, the vector may be a mammalian vector, e.g. comprising a cytomegalovirus (CMV) or SV40 promoter to drive protein expression. In some embodiments, the vector comprises a CMV (e.g. mCMV), SV40, RSV or PGK promoter. In some embodiments, the polynucleotide according to the present disclosure (e.g. the vector according to the present disclosure) comprises a CMV promoter, a CAG promoter, a hEF1a promoter, a hUbiC promoter, an RSV promoter, a TK promoter, a PGK promoter, or a CAG minimal promoter. In some embodiments, the polynucleotide according to the present disclosure (e.g. the vector according to the present disclosure) comprises a promoter having a nucleotide sequence comprising, or consisting of, a nucleotide sequence having at least 80% (e.g. one of ≥85%, ≥90%, ≥91%, ≥92%, ≥93%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99% or 100%) sequence identity to SEQ ID NO:201, 202, 203, 204, 205, 206, 207 or 208. In some embodiments, a vector is selected based on tropism for a cell type / tissue / organ to which it is desired to deliver the polynucleotide according to the present disclosure. In some embodiments, a vector is selected based on tropism for a cell type / tissue / organ in which it is desired to express the polypeptide of interest. For example, it may be desired to deliver the polynucleotide to, and / or express the polypeptide of interest in, a cell type / tissue / organ affected by a disease / condition to be treated / prevented in accordance with the present disclosure (e.g. a cell type / tissue / organ in which the symptoms of the disease / condition manifest). For example, it might be desirable to deliver a polynucleotide of the present disclosure encoding a polypeptide of interest to neuronal cells / tissue, and vectors having a tropism for such cells / tissue may be employed in such instances (i.e. neurotropic vectors). In preferred embodiments, the vector is an adeno-associated virus (AAV) vector. Adeno-associated virus vectors and their use to vector gene therapy is reviewed e.g. in Wang et al., Nat. Rev. Drug Discov. (2019) 18: 358-378 and Li and Samulski, Nat. Rev. Genet. (2020) 12: 255-272, both of which are hereby incorporated by reference in their entirety. In some embodiments, a vector may be an adeno-associated virus vector described in Wang et al., Nat. Rev. Drug Discov. (2019) 18: 358-378. In some embodiments, a vector may be an adeno-associated virus vector described in Li and Samulski, Nat. Rev. Genet. (2020) 12: 255-272. In some embodiments, the vector is a self-complementary adeno-associated virus (scAAV) vector. Self- complementary adeno-associated virus vectors are described e.g. in McCarty, Mol Ther. (2008) 16(10):1648-56, which is hereby incorporated by reference in its entirety. Conventional AAV have a P37829 single-stranded DNA genome, and depend on the DNA replication machinery of a transduced cell to synthesise the complementary strand, delaying transgene expression. By contrast, scAAV contain complementary sequences that spontaneously anneal upon infection, eliminating the requirement for DNA synthesis in the transduced host cell. Compared to classical, single-stranded AAV vectors, scAAV vectors have been shown to provide for accelerated onset of transgene expression, and an increased level of transgene expression. In some embodiments, a vector may be an adeno-associated viral vector of one of the following serotypes: AAV9 (including AAV9 variants AAV-PHP.B and AAV9.45), AAV1, AAV2 (including AAV2 variant AAV2i8), AAV5, AAV6, AAV8, AAV10 or AAVrh74. In some embodiments, a vector may be an adeno-associated viral vector of one of the following serotypes: AAV9 (including AAV9 variants AAV- PHP.B and AAV9.45), AAV1, AAV2 (including AAV2 variants AAV2.7m8 and AAV2i8), AAV5, AAV6, AAV8, AAV10 or AAVrh74. In some embodiments, the vector is an AAV9 vector. In some embodiments a vector comprises modification to increase binding to and / or transduction of a cell-type of interest (i.e. as compared to the level of binding / transduction by the unmodified vector). In some embodiments modification is to a capsid protein. In some embodiments a vector comprises a capsid protein comprising a cell-targeting peptide. In some embodiments the cell-targeting peptide is a cell-targeting peptide described in Büning and Srivastava, Molecular Therapy: Methods & Clinical Development (2019) 12: 248-265, which is hereby incorporated by reference in its entirety, e.g. a cell-targeting peptide shown in Table 1, 2, 3 or 4 thereof. In some embodiments a vector comprises a capsid protein comprising substitution to one or more tyrosine residues, e.g. one or more surface-exposed tyrosine residues. In some embodiments, one or more tyrosine residues of the capsid protein are substituted with phenylalanine. In some embodiments a vector comprises a capsid protein in which one or more tyrosine residues are substituted with another amino acid as described in Iida et al., Biomed Res Int. (2013) 2013: 974819, which is hereby incorporated by reference in its entirety. In some embodiments, a vector may be an adeno-associated virus vector described in Büning and Srivastava, supra. In some embodiments, a vector may be an adeno-associated virus vector described in Iida et al., supra. In some embodiments the vector comprises a control element for inducible expression of the polynucleotide of the disclosure. A sequence for controlling expression of the polynucleotide may provide for expression of the polynucleotide by cells of a particular type or tissue. For example, expression may be under the control of a cell type- or tissue-specific promoter. P37829 Promoters for cell type- or tissue-specific expression of a polynucleotide in accordance with the present disclosure can be selected in accordance with a disease / condition to be treated / prevented. For example, the promoter may drive expression in a cell type / tissue / an organ affected by the disease / condition (e.g. a cell type / tissue / an organ in which the symptoms of the disease / condition manifest). In some embodiments, a promoter may provide for expression of the polynucleotide in neuronal cells / tissue. In some embodiments, a promoter may be a neuron-specific promoter (e.g. a CaMKII, NSE or SynI-miniCMV promoter) In some embodiments, a promoter may provide for expression of the polynucleotide in muscle cells / tissue (e.g. cardiac and / or skeletal muscle cells / tissue). In some embodiments, a promoter may be a cardiac or cardiomyocte-specific promoter (e.g. a cTNT, α-MHC or MLC2v promoter). In some embodiments, a promoter may be a skeletal muscle / striated muscle cell- specific promoter (e.g. a MCK, MHCK7 or desmin promoter). In some embodiments, a promoter may be a vascular endothelial cell-specific promoter (e.g. a Tie2 promoter). In some embodiments, a promoter may be a vascular smooth muscle cell-specific promoter (e.g. a SM22a promoter). In some embodiments, a promoter may be a monocyte / macrophage-specific promoter (e.g. a LysM promoter). A sequence for controlling expression of the polynucleotide may provide for expression of the polynucleotide in response to e.g. a given agent / signal. For example, expression may be under the control of inducible promoter. The agent may provide for inducible expression of the polynucleotide in vivo by administration of the agent to a subject having been administered with a modified cell according to the disclosure, or ex vivo / in vitro by administration of the agent to cells in culture ex vivo or in vitro. In some embodiments a polynucleotide or vector according to the present disclosure may employ a conditional expression system for controlling expression of the polynucleotide by cells comprising the polynucleotide / vector. ‘Conditional expression’ may also be referred to herein as ‘inducible expression’, and refers to expression contingent on certain conditions, e.g. the presence of a particular agent. Conditional expression systems are well known in the art and are reviewed e.g. in Ryding et al. Journal of Endocrinology (2001) 171, 1-14, which is hereby incorporated by reference in its entirety. Cells The present disclosure also provides a cell comprising or expressing a polynucleotide according to the present disclosure. Also provided is a cell comprising or expressing vector according to the present disclosure. A polynucleotide according to the present disclosure (e.g. a polyribonucleotide) may be produced within a cell by transcription from a polynucleotide (e.g. a polydeoxyribonucleotide) encoding the polynucleotide. The cell may be a eukaryotic cell, e.g. a mammalian cell. The mammal may be a primate (rhesus, cynomolgous, non-human primate or human) or a non-human mammal (e.g. rabbit, guinea pig, rat, mouse or other rodent (including any animal in the order Rodentia), cat, dog, pig, sheep, goat, cattle (including cows, e.g. dairy cows, or any animal in the order Bos), horse (including any animal in the order Equidae), donkey, and non-human primate). In preferred embodiments, the cell may be a human cell. P37829 The cell may be an immune cell. The cell may be a cell of hematopoietic origin, e.g. a neutrophil, eosinophil, basophil, dendritic cell, lymphocyte, or monocyte. The lymphocyte may be e.g. a T cell, B cell, NK cell, NKT cell or innate lymphoid cell (ILC), or a precursor thereof. The cell may express e.g. CD3 polypeptides (e.g. CD3γ CD3ε CD3ζ or CD3δ), TCR polypeptides (TCRα or TCRβ), CD27, CD28, CD4 or CD8. In some embodiments, the cell is a T cell. In some embodiments, the T cell is a CD3+ T cell. In some embodiments, the T cell is a CD3+, CD8+ T cell. In some embodiments, the T cell is a cytotoxic T cell (e.g. a cytotoxic T lymphocyte (CTL)). The present disclosure also provides a method for producing a cell comprising or expressing a polynucleotide / vector according to the present disclosure, the method comprising introducing a polynucleotide / vector of the present disclosure into a cell. In some embodiments, introducing a polynucleotide / vector according to the present disclosure into a cell comprises transformation, transfection, electroporation or transduction (e.g. adeno-associated viral transduction). In some embodiments, the polynucleotide / vector is introduced to the cell in vivo, e.g. by administration of a vector according to the present disclosure (e.g. a viral vector, e.g. an adeno-associated viral vector) to a subject. In some embodiments, the polynucleotide / vector is introduced into cells in culture ex vivo or in vitro. Any suitable method may be employed to produce a cell according to the present disclosure. Such methods may comprise nucleic acid transfer for permanent (i.e. stable) or transient expression of the polynucleotide of the present disclosure. In some embodiments, following introduction into a cell, the polynucleotide may be integrated into or form part of the genomic DNA of the cell. In some embodiments, following introduction into a cell, the polynucleotide may be maintained extrachromosomally. Any suitable genetic engineering platform may be used, and include gammaretroviral vectors, lentiviral vectors, adenovirus vectors, DNA transfection, transposon-based gene delivery and RNA transfection, for example as described in Maus et al., Annu Rev Immunol. (2014) 32:189-225, hereby incorporated by reference in its entirety. Methods also include those described e.g. in Wang and Rivière Mol Ther Oncolytics. (2016) 3:16015, which is hereby incorporated by reference in its entirety. Suitable methods for introducing nucleic acid(s) / vector(s) into cells include transduction, transfection and electroporation. In some embodiments, the methods additionally comprise maintaining the cell under conditions suitable for expression of the polynucleotide / vector by the cell. The present disclosure also provides cells obtained or obtainable by the methods according to the present disclosure. Compositions The present disclosure also provides compositions comprising the polynucleotides, vectors and cells described herein. In particular, the present disclosure provides pharmaceutical compositions and medicaments comprising the polynucleotides, vectors and cells of the present disclosure. P37829 Such compositions may comprise the relevant article (i.e. the polynucleotide / vector / cell) in a formulation suitable for clinical use. The present disclosure is concerned in particular with pharmaceutical compositions / medicaments comprising polynucleotides and vectors according to the present disclosure. The compositions of the present disclosure may comprise one or more pharmaceutically-acceptable carriers (e.g. liposomes, micelles, microspheres, nanoparticles), diluents / excipients (e.g. starch, cellulose, a cellulose derivative, a polyol, dextrose, maltodextrin, magnesium stearate), adjuvants, fillers, buffers, preservatives (e.g. vitamin A, vitamin E, vitamin C, retinyl palmitate, selenium, cysteine, methionine, citric acid, sodium citrate, methyl paraben, propyl paraben), anti-oxidants (e.g. vitamin A, vitamin E, vitamin C, retinyl palmitate, selenium), lubricants (e.g. magnesium stearate, talc, silica, stearic acid, vegetable stearin), binders (e.g. sucrose, lactose, starch, cellulose, gelatin, polyethylene glycol (PEG), polyvinylpyrrolidone (PVP), xylitol, sorbitol, mannitol), stabilisers, solubilisers, surfactants (e.g., wetting agents), masking agents or colouring agents (e.g. titanium oxide). The term ‘pharmaceutically-acceptable’ as used herein pertains to compounds, ingredients, materials, compositions, dosage forms, etc., which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of the subject in question (e.g. a human subject) without excessive toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit / risk ratio. Each carrier, diluent, excipient, adjuvant, filler, buffer, preservative, anti-oxidant, lubricant, binder, stabiliser, solubiliser, surfactant, masking agent, colouring agent, flavouring agent or sweetening agent of a composition according to the present disclosure must also be ‘acceptable’ in the sense of being compatible with the other ingredients of the formulation. Suitable carriers, diluents, excipients, adjuvants, fillers, buffers, preservatives, anti-oxidants, lubricants, binders, stabilisers, solubilisers, surfactants, masking agents, colouring agents, flavouring agents or sweetening agents can be found in standard pharmaceutical texts, for example, Remington’s ‘The Science and Practice of Pharmacy’ (Ed.(A)Adejare), 23rd Edition (2020), Academic Press. The pharmaceutical compositions / medicaments according to the present disclosure may be formulated for administration to a subject, e.g. administration via a route of administration as appropriate for the nature of the therapeutic agent and the disease to be treated / prevented. In some embodiments, a pharmaceutical composition / medicament may be formulated for parenteral, systemic, topical, intracavitary, intravascular, intravenous, intra-arterial, intramuscular, intrathecal, intraocular, intraconjunctival, intratumoral, subcutaneous, intradermal,, oral or transdermal administration. In some embodiments, a pharmaceutical composition / medicament may be formulated for administration by injection or infusion, or administration by ingestion. Medicaments and pharmaceutical compositions may be formulated for administration to a blood vessel, or to a tissue / organ of interest (e.g. a tissue / organ affected by a disease / condition, e.g. a tissue / organ in which symptoms of the disease / condition manifest). The pharmaceutical compositions / medicaments may comprise the polynucleotide / vector / cell in a sterile or isotonic medium. The pharmaceutical compositions / medicaments may be provided in fluid, including gel, P37829 form. Fluid formulations may be formulated for administration by injection or infusion (e.g. via cannula) to a blood vessel, or a selected region of the human or animal body. The pharmaceutical compositions / medicaments may be provided in solid form, e.g. in lyophilised form. The present disclosure also provides methods for producing pharmaceutical compositions / medicaments according to the present disclosure. Such methods may comprise mixing a polynucleotide / vector / cell described herein with a pharmaceutically-acceptable carrier, diluent, excipient, adjuvant, filler, buffer, preservative, anti-oxidant, lubricant, binder, stabiliser, solubiliser, surfactant, masking agent, colouring agent, flavouring agent or sweetening agent. Such methods generally include the step of bringing into association the polynucleotide / vector / cell with a carrier which constitutes one or more accessory ingredients. In general, the compositions are prepared by uniformly and intimately bringing into association the active compound with carriers (e.g., liquid carriers, finely divided solid carrier, etc.), and then shaping the product, if necessary. Polynucleotides, vectors, cells and compositions according to the present disclosure may be modified and / or formulated to facilitate delivery to, and / or uptake by, a cell type / tissue / organ of interest (e.g. a cell type / tissue / organ in which symptoms of a disease / condition manifest). Strategies for targeted delivery of polynucleotides are reviewed e.g. in Li et al., Int. J. Mol. Sci. (2015) 16: 19518-19536 and Fu et al., Bioconjug Chem. (2014) 25(9): 1602-1608, which are hereby incorporated by reference in their entirety. In some embodiments, articles of the present disclosure may be encapsulated in a nanoparticle or a liposome. In some embodiments, articles of the present disclosure may be (covalently or non-covalently) associated with a cell-penetrating peptide (e.g. a protein transduction domain, trojan peptide, arginine-rich peptide, vectocell peptide), a cationic polymer, a cationic lipid or a viral carrier. Nanoparticles may be organic, e.g. micelles, liposomes, proteins, solid-lipid particles, solid polymer particles, dendrimers, and polymer therapeutics. Nanoparticles may be inorganic, e.g. such as nanotubes or metal particles, optionally with organic molecules added. In some embodiments, a nanoparticle is a nanoparticle described in Chen et al., Mol Ther Methods Clin Dev. (2016) 3:16023, which is hereby incorporated by reference in its entirety. In some embodiments, a nanoparticle is a PLGA, polypeptide, poly(β-amino ester), DOPE, β-cyclodextrin-containing polycation, linear PEI, PAMAM dendrimer, branched PEI, chitosan or polyphosophoester nanoparticle. In some embodiments, polynucleotides and vectors according to the present disclosure comprise modification to incorporate one or more moieties facilitating delivery to, and / or uptake by, a cell type, organ or tissue of interest (e.g. a cell type / tissue / organ in which symptoms of a disease / condition manifest). In some embodiments, polynucleotides or vectors according to the present disclosure are linked (e.g. chemically conjugated to) one or more moieties facilitating delivery to, and / or uptake by, a cell type, tissue or organ of interest. P37829 Moieties facilitating delivery to, and / or uptake by, cell types, tissues or organs of interest are described e.g. in Benizri et al., Bioconjug Chem. (2019) 30(2): 366–383, which is hereby incorporated by reference in its entirety. Such moieties include e.g. N-acetylgalactosamine (GalNAc), α-tocopherol, cell-penetrating peptides, nucleic acid aptamers, antibodies and antigen-binding fragments / derivatives thereof, cholesterol, squalene, polyethylene glycol (PEG), fatty acids (e.g. palmitic acid) and nucleolipid moieties. Articles of the present disclosure may be formulated in a sustained release delivery system, in order to release the polynucleotide, vector, cell or composition at a predetermined rate. Sustained release delivery systems may maintain a constant drug / therapeutic / prophylactic concentration for a specified period of time. In some embodiments, articles of the present disclosure are formulated in a liposome, gel, implant, device, or drug-polymer conjugate e.g. hydrogel. In some embodiments, a composition according to the present disclosure may further comprise a splicing modifier that promotes SMN2 exon 7 inclusion (e.g. as described herein). Therapeutic / prophylactic applications The polynucleotides, vectors, cells and compositions of the present disclosure find use in therapy and prophylaxis. Accordingly, the present disclosure provides a polynucleotide, vector, cell or composition described herein for use in a method of medical treatment or prophylaxis. Also provided is a polynucleotide, vector, cell or composition described herein for use in a method of treating or preventing a disease / condition described herein. Also provided is the use of a polynucleotide, vector, cell or composition described herein in the manufacture of a medicament for treating or preventing a disease or condition described herein. Also provided is a method of treating or preventing a disease or condition described herein, comprising administering to a subject a therapeutically- or prophylactically- effective amount of a polynucleotide, vector, cell or composition described herein. The intervention described in the preceding paragraph may be effective to reduce the development or progression of a disease / condition, alleviate the symptoms of a disease / condition or reduce the pathology of a disease / condition. The intervention may be effective to prevent progression of the disease / condition, e.g. to prevent worsening of, or to slow the rate of development of, the disease / condition. In some embodiments, the intervention may lead to an improvement in the disease / condition, e.g. a reduction in the symptoms of the disease / condition or reduction in some other correlate of the severity / activity of the disease / condition. In some embodiments, the intervention may prevent progression / development of the disease / condition a later stage (e.g. a chronic stage). It will be appreciated that the polynucleotides, vectors, cells and compositions described herein may be used for the treatment / prevention of any disease / condition that would derive therapeutic or prophylactic benefit from an increase in the level of the polypeptide of interest (i.e. the polypeptide of interest encoded by the polynucleotide). P37829 For example, the disease / condition may be a disease / condition associated with and / or characterised by deficiency / insufficiency of the polypeptide of interest. Deficiency / insufficiency of the polypeptide of interest may be positively associated with the onset, development or progression of the disease / condition, and / or positively associated with the severity of one or more symptoms of the disease / condition. Deficiency / insufficiency of the polypeptide of interest may be a risk factor for the onset, development or progression of the disease / condition. The disease / condition may be characterised by a decreased level of expression or activity of the polypeptide of interest, e.g. as compared to the level of expression / activity in the absence of the disease / condition. In some embodiments, the disease / condition may be characterised by a decrease in the number / proportion / activity of cells expressing the polypeptide of interest, e.g. as compared to the level / number / proportion / activity in the absence of the disease / condition (e.g. in a healthy subject, or in equivalent non-diseased tissue). By way of illustration, in some embodiments, the polypeptide of interest may be MeCP2, and the disease / condition to be treated / prevented in accordance with the present disclosure may be a disease / condition caused by deficiency / insufficiency of MeCP2, e.g. Rett syndrome. By way of further example, in embodiments wherein the polypeptide of interest is a polypeptide capable of inhibiting the expression and / or activity of a target antigen of interest, the disease / condition may be a disease / condition in which the target antigen, or cells comprising / expressing the target antigen are pathologically-implicated, e.g. a disease / condition in which an increased level / activity of the target antigen, or an increase in the number / proportion / activity of cells comprising / expressing the target antigen is positively associated with the onset, development or progression of the disease / condition, and / or severity of one or more symptoms of the disease / condition. In some embodiments, an increased level / activity of the target antigen, or an increase in the number / proportion / activity of cells comprising / expressing the target antigen may be a risk factor for the onset, development or progression of the disease / condition. The disease / condition may be characterised by an increase in the level of expression or activity of the target antigen, e.g. as compared to the level of expression / activity in the absence of the disease / condition. In some embodiments, the disease / condition may be characterised by an increase in the number / proportion / activity of cells expressing the target antigen, e.g. as compared to the level / number / proportion / activity in the absence of the disease / condition (e.g. in a healthy subject, or in equivalent non-diseased tissue). Therapeutic / prophylactic intervention in accordance with the present disclosure may achieve one or more of the following in a subject (compared to an equivalent untreated subject, or subject treated with an appropriate control): a reduction in the level of the target antigen; a reduction in the activity of the target antigen; and / or a reduction in the number / proportion / activity of cells comprising / expressing the target antigen. By way of further example, the disease / condition may be a disease / condition to be treated by nucleic acid editing, and the polypeptide of interest may be a constituent protein of an appropriate site-specific nuclease nucleic acid editing system. The present disclosure provides the articles of the present disclosure for use, uses of articles of the present disclosure, and methods comprising administering polynucleotides, vectors, cells and P37829 compositions according to the present disclosure to a subject (e.g. a subject in need of treatment). In some embodiments, the methods comprise administering to the subject a splicing modifier that promotes SMN2 exon 7 inclusion (e.g. a splicing modifier that promotes SMN2 exon 7 inclusion as described herein). Administration of the articles of the present disclosure is preferably in a ‘therapeutically-effective’ or ‘prophylactically-effective’ amount, this being sufficient to show therapeutic or prophylactic benefit to the subject. The actual amount administered, and rate and time-course of administration, will depend on the nature and severity of the disease / condition and the particular article administered. Prescription of treatment, e.g. decisions on dosage etc., is within the responsibility of general practitioners and other medical doctors, and typically takes account of the disease / disorder to be treated, the condition of the individual subject, the site of delivery, the method of administration and other factors known to practitioners. Examples of the techniques and protocols mentioned above can be found in Remington’s ‘The Science and Practice of Pharmacy’ (ed.(A)Adejare), 23rd Edition (2020), Academic Press. Administration of the articles of the present disclosure may be parenteral, systemic, intravenous, intra- arterial, intramuscular, intracavitary, intrathecal, intraocular, intravitreal, intraconjunctival, subretinal, suprachoroidal, subcutaneous, intradermal, intrathecal, oral, nasal, topical or transdermal. Administration may be by injection or infusion. Administration of the articles of the present disclosure may be intratumoral. In some cases, the articles of the present disclosure may be formulated for targeted delivery to specific cells, a tissue, an organ and / or a tumor. Multiple doses of an article of the present disclosure may be provided. Multiple doses may be separated by a predetermined time interval, which may be selected to be one of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, or 31 days, or 1, 2, 3, 4, 5, or 6 months. In some embodiments, the present disclosure provides the articles of the present disclosure for use, uses of articles of the present disclosure, and methods comprising administering: (i) a polynucleotide, vector, cell or composition according to the present disclosure, and (ii) a splicing modifier that promotes SMN2 exon 7 inclusion, to a subject (e.g. a subject in need of treatment). In embodiments in accordance with aspects of the preceding paragraph, provision of (i) and (ii) may be as a combination therapy. In some embodiments, (i) and (ii) may be provided simultaneously or sequentially. Simultaneous administration refers to administration of the two or more agents (e.g. a polynucleotide, vector, cell or composition according to the present disclosure, and a splicing modifier that promotes SMN2 exon 7 inclusion) together, for example as a pharmaceutical composition containing both agents (i.e. as a combined preparation), or immediately after each other (e.g. within 1, 4, 6, 8 or 12 hours), and optionally via the same route of administration, e.g. to the same artery, vein or other blood vessel. Sequential administration refers to administration of one of the agents followed after a given time interval P37829 by separate administration of another agent. It is not required that the agents are administered by the same route, although this is the case in some embodiments. The time interval may be any time interval. In some embodiments, a splicing modifier that promotes SMN2 exon 7 inclusion is administered to a subject after administration of a polynucleotide, vector, cell or composition according to the present disclosure. In some embodiments, a polynucleotide, vector, cell or composition according to the present disclosure is administered to a subject, and a splicing modifier that promotes SMN2 exon 7 inclusion is administered continuously to the subject thereafter. In some embodiments, the splicing modifier that promotes SMN2 exon 7 inclusion is administered in a quantity, and / or with a periodicity, selected to achieve a desired level of expression of the polypeptide of interest. That is, in some embodiments the quantity of, and / or periodicity with which, a splicing modifier that promotes SMN2 exon 7 inclusion administered to a subject in accordance with the present disclosure is selected to achieve a desired level of expression of the polypeptide of interest. In some embodiments, the quantity of, and / or periodicity with which, a splicing modifier that promotes SMN2 exon 7 inclusion is administered to a subject is adjusted through the course of its administration to change (i.e. decrease or increase) the level of expression of the polypeptide of interest in the subject. In embodiments wherein the polynucleotide of the disclosure is an ON-switch polynucleotide, the quantity and / or periodicity of administration of a splicing modifier that promotes SMN2 exon 7 inclusion may be increased to increase the level of expression of the polypeptide of interest. Conversely, the quantity and / or periodicity of administration of a splicing modifier that promotes SMN2 exon 7 inclusion may be decreased to decrease the level of expression of the polypeptide of interest. In embodiments wherein the polynucleotide of the disclosure is an OFF-switch polynucleotide, the quantity and / or periodicity of administration of a splicing modifier that promotes SMN2 exon 7 inclusion may be decreased to increase the level of expression of the polypeptide of interest. Conversely, the quantity and / or periodicity of administration of a splicing modifier that promotes SMN2 exon 7 inclusion may be increased to decrease the level of expression of the polypeptide of interest. Further methods The present disclosure also provides a method for modifying a cell to comprise or express a polynucleotide according to the present disclosure, comprising introducing into a cell a polynucleotide or vector according to the present disclosure. In some embodiments, introducing a polynucleotide or vector according to the present disclosure into a cell comprises transformation, transfection, electroporation or transduction (e.g. retroviral transduction). Transfection relates to the process of introducing nucleic acid into cells using means other than viral infection and is hence a non-viral method. Transfection may be performed by physical / mechanical methods (including electroporation, sonoporation, magnetofection, gene microinjection and laser irradiation) or chemical methods (liposomal-based or non-liposomal based). Liposomal-based transfection P37829 reagents are chemicals which enable the formation of positively charged lipid aggregates, which can then merge with the phospholipid bilayer of the cell to facilitate the entry of foreign genetic material. Examples of liposomal-based transfection reagents include, but are not limited to Oligofectamine®, Lipofectamine® and DharmaFECT®. Non-liposomal transfection reagents include, but are not limited to, calcium phosphate, nanoparticles, polymers, dendrimers and non-liposomal lipids. One example of a non- liposomal transfection reagent is polyethylenimine (PEI). Electroporation may be performed e.g. as described in Koh et al., Molecular Therapy – Nucleic Acids (2013) 2, e114, which is hereby incorporated by reference in its entirety. Transduction is a process by which nucleic acids may be introduced into a cell by a virus or a viral vector. Accordingly, in some embodiments the polynucleotide is, or is comprised in, a viral vector, or the vector is a viral vector. Transduction of immune cells with viral vectors is described e.g. in Simmons and Alberola- Ila, Methods Mol Biol. (2016) 1323:99-108, which is hereby incorporated by reference in its entirety. Agents may be employed in the methods of the present disclosure to enhance the efficiency of transduction. Hexadimethrine bromide (polybrene) is a cationic polymer which is commonly used to improve transduction, through neutralising charge repulsion between virions and sialic acid residues expressed on the cell surface. Other agents commonly used to enhance transduction include e.g. the poloxamer-based agents such as LentiBOOST (Sirion Biotech), Retronectin (Takara), Vectofusin (Miltenyi Biotech) and also SureENTRY (Qiagen) and ViraDuctin (Cell Biolabs). In some embodiments the methods comprise centrifuging the cells into which it is desired to introduce polynucleotide or vector according to the present disclosure in the presence of cell culture medium comprising viral vector(s) comprising the polynucleotide (referred to in the art as ‘spinfection’). In some embodiments, the methods comprise culturing the cell under conditions suitable for expression of the polynucleotide or vector by the cell. In some embodiments, the methods comprise culturing the cell under conditions suitable for transcription of a polydeoxyribonucleotide. In some embodiments, the methods comprise culturing the cell under conditions suitable for post-transcriptional processing (e.g. splicing) of a polyribonucleotide. In some embodiments, the methods comprise culturing the cell under conditions suitable for translation of a polypeptide from a polyribonucleotide. Methods for culturing (including generating and / or expanding) populations of cells in vitro / ex vivo – including suitable culture conditions (i.e. cell culture media, additives, stimulations, temperature, gaseous atmosphere), cell numbers, culture periods etc. – are well known to the skilled person. Conveniently, cultures of cells according to the present disclosure may be maintained at 37°C in a humidified atmosphere containing 5% CO2. The present disclosure also provides a method for modifying a cell to express a polypeptide of interest, comprising introducing into a cell a polynucleotide or vector according to the present disclosure. Where the polynucleotide is, or wherein the vector comprises / encodes, an OFF-switch, the cell may express the polypeptide of interest following introduction of the polynucleotide / vector into the cell. P37829 Where the polynucleotide is, or wherein the vector comprises / encodes, an ON-switch, the method may further comprise contacting the cell with a splicing modifier that promotes SMN2 exon 7 inclusion as described herein. Thus, in some embodiments, the method comprises (i) introducing into a cell a polynucleotide or vector according to the present disclosure; and (ii) subsequently contacting the cell with a splicing modifier that promotes SMN2 exon 7 inclusion. ‘Contacting’ a cell with a splicing modifier may comprise bringing a cell into contact with a splicing modifier in a cell culture, and may be achieved by applying the splicing modifier to the cells in culture. The present disclosure also provides a method for inhibiting expression of a polypeptide of interest in a cell. The method comprises contacting a cell comprising a polynucleotide or vector according to the present disclosure comprising / encoding an OFF-switch with a splicing modifier that promotes SMN2 exon 7 inclusion as described herein. Any suitable quantity / concentration of a splicing modifier may be employed in the methods of the present disclosure. It will be appreciated that the quantity / concentration of the splicing modifier is preferably selected such as to achieve the desired effect, i.e. increased inclusion of the SMN2 exon 7 variant nucleotide sequence in the products of splicing of the relevant polyribonucleotide. Subjects A subject in accordance with the various aspects of the present disclosure may be any animal or human. Therapeutic and prophylactic applications may be in human or animals (veterinary use). The subject to be administered with an article of the present disclosure (e.g. in accordance with therapeutic or prophylactic intervention) may be a subject in need of such intervention. The subject is preferably mammalian, more preferably human. The subject may be a non-human mammal, but is more preferably human. The subject may be male or female. The subject may be a patient. A subject may have (e.g. may have been diagnosed with) a disease or condition described herein, may be suspected of having such a disease / condition, or may be at risk of developing / contracting such a disease / condition. In embodiments according to the present disclosure, a subject may be selected for treatment according to the methods based on characterisation for one or more markers of such a disease / condition. Kits The present disclosure also provides kits of parts. In some aspects and embodiments, a kit of parts according to the present disclosure comprises (i) a polynucleotide, vector, or a pharmaceutical composition according to the present disclosure, and (ii) a splicing modifier that promotes SMN2 exon 7 inclusion. P37829 Kits of parts according to the present disclosure may comprise a predetermined quantity of articles according to (i) and / or (ii), as described in the preceding paragraph. In some embodiments, articles according to (i) and / or (ii) are provided in containers (e.g. in vials or bottles). The kit may provide articles according to (i) and / or (ii) together with instructions (e.g. a protocol) as to how to employ them in accordance with a therapeutic or prophylactic intervention as described herein. In some embodiments, the kit of parts may comprise a polynucleotide or vector according to the present disclosure, and optionally materials for introducing the polynucleotide / vector into a cell. In some embodiments, the kit of parts may comprise a system for producing a cell according to the present disclosure. In some embodiments, the kit of parts may comprise a (closed) bag cell incubation system in which a polynucleotide or vector can be introduced into a cell. In some embodiments, the kit of parts may comprise materials for formulating a polynucleotide or vector according to the present disclosure to a pharmaceutical composition, e.g. a pharmaceutically-acceptable carrier, diluent, excipient or adjuvant. In some embodiments, the kit of parts further comprises reagents, buffers and / or standards required for execution of a method according to the present disclosure. Kits according to the present disclosure may include instructions for use, e.g. in the form of an instruction booklet or leaflet. The instructions may include a protocol for performing any one or more of the methods described herein. The manufacture of kits of parts according to the present disclosure preferably follows standard procedures which are known to the person skilled in the art. Sequence identity The ‘sequence identity’ between a given nucleotide sequence (e.g. of a polynucleotide) and a reference nucleotide sequence is calculated by determining the percentage of the nucleotides in the given nucleotide sequence that are identical to those of the reference nucleotide sequence, after aligning the sequences and, if necessary, introducing gaps, to achieve the maximum percentage sequence identity between the two sequences. Similarly, ‘sequence identity’ between a given amino acid sequence (e.g. of a polypeptide) and a reference amino acid sequence is calculated by determining the percentage of the amino acids in the given amino acid sequence that are identical to those of the reference amino acid sequence, after aligning the sequences and, if necessary, introducing gaps, to achieve the maximum percentage sequence identity between the two sequences. Pairwise and multiple sequence alignment for the purposes of evaluating sequence identity between two or more nucleotide or amino acid sequences can be achieved in various ways known to a person of skill in the art, for instance, using publicly available computer software such as ClustalOmega (Söding, J. 2005, Bioinformatics 21, 951-960), T-coffee (Notredame et al.2000, J. Mol. Biol. (2000) 302, 205-217), Kalign (Lassmann and Sonnhammer 2005, BMC Bioinformatics, 6(298)) and MAFFT (Katoh and Standley 2013, Molecular Biology and Evolution, 30(4) 772–780) software. When using such software, the default parameters, e.g. for gap penalty and extension penalty, are preferably used. P37829 Sequences SEQ ID DESCRIPTION SEQUENCENO: GCX1-2AATTTCATGGTACGGCAGTGGCTATCATACTGGCTATTATX3-4G 1 SMN2 exon 6 variant consensus 1 wherein X1-2= absent or TT; X3-4= AT, CT or CA 2 SMN2 exon 6 (wildtype) ATAATTCCCCCACCACCTCCCATATGTCCAGATTCTCTTGATGATGCTGATGCTTTGGGA AGTATGTTAATTTCATGGTACATGAGTGGCTATCATACTGGCTATTATATG 45 nucleotide SMN2 exon 6 comprising 3 ATG>GGC at positions GCAATTTCATGGTACGGCAGTGGCTATCATACTGGCTATTATATG 82 to 84 (SMN2 exon 6 variant 1) GCTTAATTTCATGGTACGGCAGTGGCTATCATACTGGCTATTATCX1G 4 SMN2 exon 6 variant consensus 2 wherein X1 = T or A SMN2 exon 6 comprising ATG>GGC at positions 64 to 66, ATG>GGC at 5 positions 82 to 84 and ATAATTCCCCCACCACCTCCCATATGTCCAGATTCTCTTGATGATGCTGATGCTTTGGGA ATG>CTG at positions AGTGGCTTAATTTCATGGTACGGCAGTGGCTATCATACTGGCTATTATCTG 109 to 111 (SMN2 exon 6 variant 2) SMN2 exon 6 comprising ATG>GGC at positions 64 to 66, 6 ATG>GGC at positions ATAATTCCCCCACCACCTCCCATATGTCCAGATTCTCTTGATGATGCTGATGCTTTGGGA 82 to 84 and ATG>CAG AGTGGCTTAATTTCATGGTACGGCAGTGGCTATCATACTGGCTATTATCAG at positions 109 to 111 (SMN2 exon 6 variant 3) 7 Positions 1 to 102 of GTAAGTAATCACTCAGCATCTTTTCCTGACAATTTTTTTGTAGTTATGTGACTTTGTTTTGT SMN2 intron 6 AAATTTATAAAATACTACTTGCTTCTCTCTTTATATTACT 3’ 162 positions of SMN2 intron 6, comprising A>C TTAAAAGACTATCAACTTAATTTCTGATCATATTTTGTTGAATAAAATAAGTAAAATGTCTT 8 4 positions from the 3’ GTGAAACAAAATGCTTTTTAACATCCATATAAAGCTATCTATATATAGCTATCTATATCTAT end (position 5766 of ATAGCTATTTTTTTTAACTTCCTTTATTTTCCTTCCAG intron 6) 414 nucleotide SMN2 GTAAGTAATCACTCAGCATCTTTTCCTGACAATTTTTTTGTAGTTATGTGACTTTGTTTTGT intron 6, comprising A>C AAATTTATAAAATACTACTTGCTTCTCTCTTTATATTACTAAAAAATAAAAATAAAAAAATAC 4 po AACTGTCTGAGGCTTAAATTACTCTTGCATTGTCCCTAAGTATAATTTTAGTTAATTTTAAA 9 sitions from the 3’ end (position 5766 of AAGCTTTCATGCTATCTTAACTGCAGCCTAATAATTGTTTTCTTTGGGATAACTTTTAAAGT intron 6) (intron 6 variant ACATTAAAAGACTATCAACTTAATTTCTGATCATATTTTGTTGAATAAAATAAGTAAAATGT 1) CTTGTGAAACAAAATGCTTTTTAACATCCATATAAAGCTATCTATATATAGCTATCTATATC TATATAGCTATTTTTTTTAACTTCCTTTATTTTCCTTCCAG 264 nucleotide SMN2 intron 6, comprising A>C GTAAGTAATCACTCAGCATCTTTTCCTGACAATTTTTTTGTAGTTATGTGACTTTGTTTTGT 4 position AAATTTATAAAATACTACTTGCTTCTCTCTTTATATTACTTTAAAAGACTATCAACTTAATTT 410 s from the 3’ end (position 5766 of CTGATCATATTTTGTTGAATAAAATAAGTAAAATGTCTTGTGAAACAAAATGCTTTTTAACA intron 6) (intron 6 variant TCCATATAAAGCTATCTATATATAGCTATCTATATCTATATAGCTATTTTTTTTAACTTCCTT 2) TATTTTCCTTCCAG GATTTTX1-6AX7-8CAAAATCAAAAAGAAGGAAGGTGCTCACATTCCTTAAATATAAGGA 11 SMN2 exon 7 variant consensus 1 wherein X1-6= absent or GCCACC; X7-8= GA or TG 12 SMN2 exon 7 (wildtype)GGTTTTAGACAAAATCAAAAAGAAGGAAGGTGCTCACATTCCTTAAATTAAGGASMN2 exon 7 comprising G>A at position 2, and GATTTTAGACAAAATCAAAAAGAAGGAAGGTGCTCACATTCCTTAAATATAAGGA 13 insertion of A after position 48 (exon 7 variant 1) SMN2 exon 7 comprising 14 G>A at position 2, GATTTTGCCACCATGCAAAATCAAAAAGAAGGAAGGTGCTCACATTCCTTAAATATAAGG insertion of GCCACC A P37829 after position 6, GA>TG at positions 8 and 9, and insertion of A after position 48 (exon 7 variant 2) Positions 1 to 102 of GTAAGTCTGCCAGCATTATGAAAGTGAATCTTACTTTTGTAAAACTTTATGGTTTGTGGAA SMN2 intron 7 AACAAATGTTTTTGAACATTTAAAAAGTTCAGATGTTAGAA 3’ 150 positions of SMN2 CTTTTTTTTATTGTGATATGGGATAACCTAGGCATACTGCACTGTACACTCTGACATATGA intron 7 AGTGCTCTAGTCAAGTTTAACTGGTGTCCACAGAGGACATGGTTTAACTGGAATTCGTCA AGCCTCTGGTTCTAATTTCTCATTTGCAG GTAAGTCTGCCAGCATTATGAAAGTGAATCTTACTTTTGTAAAACTTTATGGTTTGTGGAA 252 nucleotide SMN2 AACAAATGTTTTTGAACATTTAAAAAGTTCAGATGTTAGAACTTTTTTTTATTGTGATATGG intron 7 GATAACCTAGGCATACTGCACTGTACACTCTGACATATGAAGTGCTCTAGTCAAGTTTAA CTGGTGTCCACAGAGGACATGGTTTAACTGGAATTCGTCAAGCCTCTGGTTCTAATTTCT CATTTGCAG GTAAGTCTGCCAGCATTATGAAAGTGAATCTTACTTTTGTAAAACTTTATGGTTTGTGGAA AACAAATGTTTTTGAACATTTAAAAAGTTCAGATGTTAGAAAGTTGAAAGGTTAATGTAAA ACAATCAATATTAAAGAATTTTGATGCCAAAACTATTAGATAAAAGGTTAATCTACATCCC 444 nucleotide SMN2 TACTAGAATTCTCATACTTAACTGGTTGGTTGTGTGGAAGAAACATACTTTCACAATAAAG intron 7 (wildtype) AGCTTTAGGATATGATGCCATTTTATATCACTAGTAGGCAGACCAGCAGACTTTTTTTTAT TGTGATATGGGATAACCTAGGCATACTGCACTGTACACTCTGACATATGAAGTGCTCTAG TCAAGTTTAACTGGTGTCCACAGAGGACATGGTTTAACTGGAATTCGTCAAGCCTCTGGT TCTAATTTCTCATTTGCAG X1-2AATGCTGGCATAGAGCAGCAC Positions 1 to 23 of SMN2 exon 8 consensus wherein X1-2= GA or TG; Positions 1 to 23 of SMN2 exon 8 (exon 8 GAAATGCTGGCATAGAGCAGCAC variant 1) Positions 1 to 23 of SMN2 exon 8, comprising GA>TG at TGAATGCTGGCATAGAGCAGCAC positions 1 to 2 (exon 8 variant 2) GCCACCATGGCAATTTCATGGTACGGCAGTGGCTATCATACTGGCTATTATATGGTAAGT AATCACTCAGCATCTTTTCCTGACAATTTTTTTGTAGTTATGTGACTTTGTTTTGTAAATTT ATAAAATACTACTTGCTTCTCTCTTTATATTACTTTAAAAGACTATCAACTTAATTTCTGAT CATATTTTGTTGAATAAAATAAGTAAAATGTCTTGTGAAACAAAATGCTTTTTAACATCCAT ATAAAGCTATCTATATATAGCTATCTATATCTATATAGCTATTTTTTTTAACTTCCTTTATTT pMM112 ON-switch TCCTTCCAGGATTTTAGACAAAATCAAAAAGAAGGAAGGTGCTCACATTCCTTAAATATAA GGAGTAAGTCTGCCAGCATTATGAAAGTGAATCTTACTTTTGTAAAACTTTATGGTTTGTG GAAAACAAATGTTTTTGAACATTTAAAAAGTTCAGATGTTAGAACTTTTTTTTATTGTGATA TGGGATAACCTAGGCATACTGCACTGTACACTCTGACATATGAAGTGCTCTAGTCAAGTT TAACTGGTGTCCACAGAGGACATGGTTTAACTGGAATTCGTCAAGCCTCTGGTTCTAATT TCTCATTTGCAGGA GCAATTTCATGGTACGGCAGTGGCTATCATACTGGCTATTATATGGTAAGTAATCACTCA GCATCTTTTCCTGACAATTTTTTTGTAGTTATGTGACTTTGTTTTGTAAATTTATAAAATAC TACTTGCTTCTCTCTTTATATTACTTTAAAAGACTATCAACTTAATTTCTGATCATATTTTGT TGAATAAAATAAGTAAAATGTCTTGTGAAACAAAATGCTTTTTAACATCCATATAAAGCTAT CTATATATAGCTATCTATATCTATATAGCTATTTTTTTTAACTTCCTTTATTTTCCTTCCAGG pMM130 ON-switch ATTTTAGACAAAATCAAAAAGAAGGAAGGTGCTCACATTCCTTAAATATAAGGAGTAAGT CTGCCAGCATTATGAAAGTGAATCTTACTTTTGTAAAACTTTATGGTTTGTGGAAAACAAA TGTTTTTGAACATTTAAAAAGTTCAGATGTTAGAACTTTTTTTTATTGTGATATGGGATAAC CTAGGCATACTGCACTGTACACTCTGACATATGAAGTGCTCTAGTCAAGTTTAACTGGTG TCCACAGAGGACATGGTTTAACTGGAATTCGTCAAGCCTCTGGTTCTAATTTCTCATTTG CAGGA ATAATTCCCCCACCACCTCCCATATGTCCAGATTCTCTTGATGATGCTGATGCTTTGGGA AGTGGCTTAATTTCATGGTACGGCAGTGGCTATCATACTGGCTATTATCTGGTAAGTAAT CACTCAGCATCTTTTCCTGACAATTTTTTTGTAGTTATGTGACTTTGTTTTGTAAATTTATA AAATACTACTTGCTTCTCTCTTTATATTACTAAAAAATAAAAATAAAAAAATACAACTGTCT GAGGCTTAAATTACTCTTGCATTGTCCCTAAGTATAATTTTAGTTAATTTTAAAAAGCTTTC pMM59 ON-switch ATGCTATCTTAACTGCAGCCTAATAATTGTTTTCTTTGGGATAACTTTTAAAGTACATTAAA AGACTATCAACTTAATTTCTGATCATATTTTGTTGAATAAAATAAGTAAAATGTCTTGTGAA ACAAAATGCTTTTTAACATCCATATAAAGCTATCTATATATAGCTATCTATATCTATATAGC AGGAAGGTGCTCACATTCCTTAAATATAAGGAGTAAGTCTGCCAGCATTATGAAAGTGAA TCTTACTTTTGTAAAACTTTATGGTTTGTGGAAAACAAATGTTTTTGAACATTTAAAAAGTT CAGATGTTAGAAAGTTGAAAGGTTAATGTAAAACAATCAATATTAAAGAATTTTGATGCCA P37829 AAACTATTAGATAAAAGGTTAATCTACATCCCTACTAGAATTCTCATACTTAACTGGTTGG TTGTGTGGAAGAAACATACTTTCACAATAAAGAGCTTTAGGATATGATGCCATTTTATATC ACTAGTAGGCAGACCAGCAGACTTTTTTTTATTGTGATATGGGATAACCTAGGCATACTG CACTGTACACTCTGACATATGAAGTGCTCTAGTCAAGTTTAACTGGTGTCCACAGAGGAC ATGGTTTAACTGGAATTCGTCAAGCCTCTGGTTCTAATTTCTCATTTGCAGGAAATGCTG GCATAGAGCAGCAC ATAATTCCCCCACCACCTCCCATATGTCCAGATTCTCTTGATGATGCTGATGCTTTGGGA AGTGGCTTAATTTCATGGTACGGCAGTGGCTATCATACTGGCTATTATCAGGTAAGTAAT CACTCAGCATCTTTTCCTGACAATTTTTTTGTAGTTATGTGACTTTGTTTTGTAAATTTATA AAATACTACTTGCTTCTCTCTTTATATTACTAAAAAATAAAAATAAAAAAATACAACTGTCT GAGGCTTAAATTACTCTTGCATTGTCCCTAAGTATAATTTTAGTTAATTTTAAAAAGCTTTC ATGCTATCTTAACTGCAGCCTAATAATTGTTTTCTTTGGGATAACTTTTAAAGTACATTAAA AGACTATCAACTTAATTTCTGATCATATTTTGTTGAATAAAATAAGTAAAATGTCTTGTGAA ACAAAATGCTTTTTAACATCCATATAAAGCTATCTATATATAGCTATCTATATCTATATAGC pMM198 ON-switch TATTTTTTTTAACTTCCTTTATTTTCCTTCCAGGATTTTAGACAAAATCAAAAAGAAGGAAG GTGCTCACATTCCTTAAATATAAGGAGTAAGTCTGCCAGCATTATGAAAGTGAATCTTACT TTTGTAAAACTTTATGGTTTGTGGAAAACAAATGTTTTTGAACATTTAAAAAGTTCAGATGT TAGAAAGTTGAAAGGTTAATGTAAAACAATCAATATTAAAGAATTTTGATGCCAAAACTAT TAGATAAAAGGTTAATCTACATCCCTACTAGAATTCTCATACTTAACTGGTTGGTTGTGTG GAAGAAACATACTTTCACAATAAAGAGCTTTAGGATATGATGCCATTTTATATCACTAGTA GGCAGACCAGCAGACTTTTTTTTATTGTGATATGGGATAACCTAGGCATACTGCACTGTA CACTCTGACATATGAAGTGCTCTAGTCAAGTTTAACTGGTGTCCACAGAGGACATGGTTT AACTGGAATTCGTCAAGCCTCTGGTTCTAATTTCTCATTTGCAGTGAATGCTGGCATAGA GCAGCAC GATTTTAGACAAAATCAAAX1AGAAGGAAGGTGCTCACATTCCTTAAATATAAGGA SMN2 exon 7 variant consensus 2 wherein X1 = absent or A SMN2 exon 7 comprising G>A at position 2, comprising deletion of GATTTTAGACAAAATCAAAAGAAGGAAGGTGCTCACATTCCTTAAATATAAGGA position 20, and comprising insertion of A after position 48 (exon 7 variant 3) GCAATTTCATGGTACGGCAGTGGCTATCATACTGGCTATTATATGGTAAGTAATCACTCA GCATCTTTTCCTGACAATTTTTTTGTAGTTATGTGACTTTGTTTTGTAAATTTATAAAATAC TACTTGCTTCTCTCTTTATATTACTTTAAAAGACTATCAACTTAATTTCTGATCATATTTTGT TGAATAAAATAAGTAAAATGTCTTGTGAAACAAAATGCTTTTTAACATCCATATAAAGCTAT CTATATATAGCTATCTATATCTATATAGCTATTTTTTTTAACTTCCTTTATTTTCCTTCCAGG pMM193 OFF-switch ATTTTAGACAAAATCAAAAAGAAGGAAGGTGCTCACATTCCTTAAATATAAGGAGTAAGT CTGCCAGCATTATGAAAGTGAATCTTACTTTTGTAAAACTTTATGGTTTGTGGAAAACAAA TGTTTTTGAACATTTAAAAAGTTCAGATGTTAGAACTTTTTTTTATTGTGATATGGGATAAC CTAGGCATACTGCACTGTACACTCTGACATATGAAGTGCTCTAGTCAAGTTTAACTGGTG TCCACAGAGGACATGGTTTAACTGGAATTCGTCAAGCCTCTGGTTCTAATTTCTCATTTG CAGGAG GCAATTTCATGGTACGGCAGTGGCTATCATACTGGCTATTATATGGTAAGTAATCACTCA GCATCTTTTCCTGACAATTTTTTTGTAGTTATGTGACTTTGTTTTGTAAATTTATAAAATAC TACTTGCTTCTCTCTTTATATTACTTTAAAAGACTATCAACTTAATTTCTGATCATATTTTGT TGAATAAAATAAGTAAAATGTCTTGTGAAACAAAATGCTTTTTAACATCCATATAAAGCTAT CTATATATAGCTATCTATATCTATATAGCTATTTTTTTTAACTTCCTTTATTTTCCTTCCAGG pMM194 OFF-switch ATTTTAGACAAAATCAAAAGAAGGAAGGTGCTCACATTCCTTAAATATAAGGAGTAAGTCT GCCAGCATTATGAAAGTGAATCTTACTTTTGTAAAACTTTATGGTTTGTGGAAAACAAATG TTTTTGAACATTTAAAAAGTTCAGATGTTAGAACTTTTTTTTATTGTGATATGGGATAACCT AGGCATACTGCACTGTACACTCTGACATATGAAGTGCTCTAGTCAAGTTTAACTGGTGTC CACAGAGGACATGGTTTAACTGGAATTCGTCAAGCCTCTGGTTCTAATTTCTCATTTGCA GGAG GTAAGTAATCACTCAGCATCTTTTCCTGACAATTTTTTTGTAGTTATGTGACTTTGTTTTGT AAATTTATAAAATACTACTTGCTTCTCTCTTTATATTACTAAAAAATAAAAATAAAAAAATAC AACTGTCTGAGGCTTAAATTACTCTTGCATTGTCCCTAAGTATAATTTTAGTTAATTTTAAA AAGCTTTCATGCTATTGTTAGATTATTTTGATTATACACTTTTGAATTGAAATTATACTTTTT CTAAATAATGTTTTAATCTCTGATTTGAAATTGATTGTAGGGAATGGAAAAGATGGGATAA SMN2 intron 6 (wildtype) TTTTTCATAAATGAAAAATGAAATTCTTTTTTTTTTTTTTTTTTTTTTGAGACGGAGTCTTGC TCTGTTGCCCAGGCTGGAGTGCAATGGCGTGATCTTGGCTCACAGCAAGCTCTGCCTCC TGGATTCACGCCATTCTCCTGCCTCAGCCTCAGAGGTAGCTGGGACTACAGGTGCCTGC AATTTTTTTAATGCACAAAGATCTGGGGTAATGTGTACCACATTGAACCTTGGGGAGTAT GGCTTCAAACTTGTCACTTTATACGTTAGTCTCCTACGGACATGTTCTATTGTATTTTAGT P37829 CAGAACATTTAAAATTATTTTATTTTATTTTATTTTTTTTTTTTTTTTGAGACGGAGTCTCGC TCTGTCACCCAGGCTGGAGTACAGTGGCGCAGTCTCGGCTCACTGCAAGCTCCGCCTC CCGGGTTCACGCCATTCTCCTGCCTCAGCCTCTCCGAGTAGCTGGGACTACAGGCGCC CGCCACCACGCCCGGCTAATTTTTTTTTATTTTTAGTAGAGACGGGGTTTCACCGTGGTC TCGATCTCCTGACCTCGTGATCCACCCGCCTCGGCCTCCCAAAGTGCTGGGATTACAAG CGTGAGCCACCGCGCCCGGCCTAAAATTATTTTTAAAAGTAAGCTCTTGTGCCCTGCTAA AATTATGATGTGATATTGTAGGCACTTGTATTTTTAGTAAATTAATATAGAAGAAACAACT GACTTAAAGGTGTATGTTTTTAAATGTATCATCTGTGTGTGCCCCCATTAATATTCTTATTT AAAAGTTAAGGCCAGACATGGTGGCTTACAACTGTAATCCCAACAGTTTGTGAGGCCGA GGCAGGCAGATCACTTGAGGTCAGGAGTTTGAGACCAGCCTGGCCAACATGATGAAAC CTTGTCTCTACTAAAAATACCAAAAAAAATTTAGCCAGGCATGGTGGCACATGCCTGTAA TCCGAGCTACTTGGGAGGCTGTGGCAGGAAAATTGCTTTAATCTGGGAGGCAGAGGTTG CAGTGAGTTGAGATTGTGCCACTGCACTCCACCCTTGGTGACAGAGTGAGATTCCATCT CAAAAAAAGAAAAAGGCCTGGCACGGTGGCTCACACCTATAATCCCAGTACTTTGGGAG GTAGAGGCAGGTGGATCACTTGAGGTTAGGAGTTCAGGACCAGCCTGGCCAACATGGT GACTACTCCATTTCTACTAAATACACAAAACTTAGCCCAGTGGCGGGCAGTTGTAATCCC AGCTACTTGAGAGGTTGAGGCAGGAGAATCACTTGAACCTGGGAGGCAGAGGTTGCAG TGAGCCGAGATCACACCGCTGCACTCTAGCCTGGCCAACAGAGTGAGAATTTGCGGAG GGAAAAAAAAGTCACGCTTCAGTTGTTGTAGTATAACCTTGGTATATTGTATGTATCATGA ATTCCTCATTTTAATGACCAAAAAGTAATAAATCAACAGCTTGTAATTTGTTTTGAGATCA GTTATCTGACTGTAACACTGTAGGCTTTTGTGTTTTTTAAATTATGAAATATTTGAAAAAAA TACATAATGTATATATAAAGTATTGGTATAATTTATGTTCTAAATAACTTTCTTGAGAAATA ATTCACATGGTGTGCAGTTTACCTTTGAAAGTATACAAGTTGGCTGGGCACAATGGCTCA CGCCTGTAATCCCAGCACTTTGGGAGGCCAGGGCAGGTGGATCACGAGGTCAGGAGAT CGAGACCATCCTGGCTAACATGGTGAAACCCCGTCTCTACTAAAAGTACAAAAACAAATT AGCCGGGCATGTTGGCGGGCACCTTTTGTCCCAGCTGCTCGGGAGGCTGAGGCAGGA GAGTGGCGTGAACCCAGGAGGTGGAGCTTGCAGTGAGCCGAGATTGTGCCAGTGCACT CCAGCCTGGGCGACAGAGCGAGACTCTGTCTCAAAAAATAAAATAAAAAAGAAAGTATA CAAGTCAGTGGTTTTGGTTTTCAGTTATGCAACCATCACTACAATTTAAGAACATTTTCAT CACCCCAAAAAGAAACCCTGTTACCTTCATTTTCCCCAGCCCTAGGCAGTCAGTACACTT TCTGTCTCTATGAATTTGTCTATTTTAGATATTATATATAAACGGAATTATACGATATGTGG TCTTTTGTGTCTGGCTTCTTTCACTTAGCATGCTATTTTCAAGATTCATCCATGCTGTAGA ATGCACCAGTACTGCATTCCTTCTTATTGCTGAATATTCTGTTGTTTGGTTATATCACATTT TATCCATTCATCAGTTCATGGACATTTAGGTTGTTTTTATTTTTGGGCTATAATGAATAATG TTGCTATGAACATTCGTTTGTGTTCTTTTTGTTTTTTTGGTTTTTTGGGTTTTTTTTGTTTTG TTTTTGTTTTTGAGACAGTCTTGCTCTGTCTCCTAAGCTGGAGTGCAGTGGCATGATCTT GGCTTACTGCAAGCTCTGCCTCCCGGGTTCACACCATTCTCCTGCCTCAGCCCGACAAG TAGCTGGGACTACAGGCGTGTGCCACCATGCACGGCTAATTTTTTGTATTTTTAGTAGAG ATGGGGTTTCACCGTGTTAGCCAGGATGGTCTCGATCTCCTGACCTCGTGATCTGCCTG CCTAGGCCTCCCAAAGTGCTGGGATTACAGGCGTGAGCCACTGCACCTGGCCTTAAGT GTTTTTAATACGTCATTGCCTTAAGCTAACAATTCTTAACCTTTGTTCTACTGAAGCCACG TGGTTGAGATAGGCTCTGAGTCTAGCTTTTAACCTCTATCTTTTTGTCTTAGAAATCTAAG CAGAATGCAAATGACTAAGAATAATGTTGTTGAAATAACATAAAATAGGTTATAACTTTGA TACTCATTAGTAACAAATCTTTCAATACATCTTACGGTCTGTTAGGTGTAGATTAGTAATG AAGTGGGAAGCCACTGCAAGCTAGTATACATGTAGGGAAAGATAGAAAGCATTGAAGCC AGAAGAGAGACAGAGGACATTTGGGCTAGATCTGACAAGAAAAACAAATGTTTTAGTATT AATTTTTGACTTTAAATTTTTTTTTTATTTAGTGAATACTGGTGTTTAATGGTCTCATTTTAA TAAGTATGACACAGGTAGTTTAAGGTCATATATTTTATTTGATGAAAATAAGGTATAGGCC GGGCACGGTGGCTCACACCTGTAATCCCAGCACTTTGGGAGGCCGAGGCAGGCGGATC ACCTGAGGTCGGGAGTTAGAGACTAGCCTCAACATGGAGAAACCCCGTCTCTACTAAAA AAAATACAAAATTAGGCGGGCGTGGTGGTGCATGCCTGTAATCCCAGCTACTCAGGAGG CTGAGGCAGGAGAATTGCTTGAACCTGGGAGGTGGAGGTTGCGGTGAGCCGAGATCAC CTCATTGCACTCCAGCCTGGGCAACAAGAGCAAAACTCCATCTCAAAAAAAAAAAAATAA GGTATAAGCGGGCTCAGGAACATCATTGGACATACTGAAAGAAGAAAAATCAGCTGGGC GCAGTGGCTCACGCCGGTAATCCCAACACTTTGGGAGGCCAAGGCAGGCGAATCACCT GAAGTCGGGAGTTCCAGATCAGCCTGACCAACATGGAGAAACCCTGTCTCTACTAAAAA TACAAAACTAGCCGGGCATGGTGGCGCATGCCTGTAATCCCAGCTACTTGGGAGGCTG AGGCAGGAGAATTGCTTGAACCGAGAAGGCGGAGGTTGCGGTGAGCCAAGATTGCACC ATTGCACTCCAGCCTGGGCAACAAGAGCGAAACTCCGTCTCAAAAAAAAAAGGAAGAAA AATATTTTTTTAAATTAATTAGTTTATTTATTTTTTAAGATGGAGTTTTGCCCTGTCACCCA GGCTGGGGTGCAATGGTGCAATCTCGGCTCACTGCAACCTCCGCCTCCTGGGTTCAAG TGATTCTCCTGCCTCAGCTTCCCGAGTAGCTGTGATTACAGCCATATGCCACCACGCCC AGCCAGTTTTGTGTTTTGTTTTGTTTTTTGTTTTTTTTTTTTGAGAGGGTGTCTTGCTCTGT CCCCCAAGCTGGAGTGCAGCGGCGCGATCTTGGCTCACTGCAAGCTCTGCCTCCCAGG TTCACACCATTCTCTTGCCTCAGCCTCCCGAGTAGCTGGGACTACAGGTGCCCGCCACC ACACCCGGCTAATTTTTTTGTGTTTTTAGTAGAGATGGGGTTTCACTGTGTTAGCCAGGA TGGTCTCGATCTCCTGACCTTTTGATCCACCCGCCTCAGCCTCCCCAAGTGCTGGGATT ATAGGCGTGAGCCACTGTGCCCGGCCTAGTCTTGTATTTTTAGTAGAGTCGGGATTTCT CCATGTTGGTCAGGCTGTTCTCCAAATCCGACCTCAGGTGATCCGCCCGCCTTGGCCTC CAAAAGTGCAAGGCAAGGCATTACAGGCATGAGCCACTGTGACCGGCAATGTTTTTAAA P37829 TTTTTTACATTTAAATTTTATTTTTTAGAGACCAGGTCTCACTCTATTGCTCAGGCTGGAGT GCAAGGGCACATTCACAGCTCACTGCAGCCTTGACCTCCAGGGCTCAAGCAGTCCTCTC ACCTCAGTTTCCCGAGTAGCTGGGACTACAGTGATAATGCCACTGCACCTGGCTAATTTT TATTTTTATTTATTTATTTTTTTTTGAGACAGAGTCTTGCTCTGTCACCCAGGCTGGAGTG CAGTGGTGTAAATCTCAGCTCACTGCAGCCTCCGCCTCCTGGGTTCAAGTGATTCTCCT GCCTCAACCTCCCAAGTAGCTGGGATTAGAGGTCCCCACCACCATGCCTGGCTAATTTT TTGTACTTTCAGTAGAAACGGGGTTTTGCCATGTTGGCCAGGCTGTTCTCGAACTCCTGA GCTCAGGTGATCCAACTGTCTCGGCCTCCCAAAGTGCTGGGATTACAGGCGTGAGCCA CTGTGCCTAGCCTGAGCCACCACGCCGGCCTAATTTTTAAATTTTTTGTAGAGACAGGGT CTCATTATGTTGCCCAGGGTGGTGTCAAGCTCCAGGTCTCAAGTGATCCCCCTACCTCC GCCTCCCAAAGTTGTGGGATTGTAGGCATGAGCCACTGCAAGAAAACCTTAACTGCAGC CTAATAATTGTTTTCTTTGGGATAACTTTTAAAGTACATTAAAAGACTATCAACTTAATTTC TGATCATATTTTGTTGAATAAAATAAGTAAAATGTCTTGTGAAACAAAATGCTTTTTAACAT CCATATAAAGCTATCTATATATAGCTATCTATATCTATATAGCTATTTTTTTTAACTTCCTTT ATTTTCCTTACAG GAAATGCTGGCATAGAGCAGCACTAAATGACACCACTAAAGAAACGATCAGACAGATCT GGAATGTGAAGCGTTATAGAAGATAACTGGCCTCATTTCTTCAAAATATCAAGTGTTGGG AAAGAAAAAAGGAAGTGGAATGGGTAACTCTTCTTGATTAAAAGTTATGTAATAACCAAAT GCAATGTGAAATATTTTACTGGACTCTATTTTGAAAAACCATCTGTAAAAGACTGAGGTG SMN2 exon 8 (wildtype) GGGGTGGGAGGCCAGCACGGTGGTGAGGCAGTTGAGAAAATTTGAATGTGGATTAGAT TTTGAATGATATTGGATAATTATTGGTAATTTTATGAGCTGTGAGAAGGGTGTTGTAGTTT ATAAAAGACTGTCTTAATTTGCATACTTAAGCATTTAGGAATGAAGTGTTAGAGTGTCTTA AAATGTTTCAAATGGTTTAACAAAATGTATGTGAGGCGTATGTGGCAAAATGTTACAGAAT CTAACTGGTGGACATGGCTGTTCATTGTACTGTTTTTTTCTATCTTCTATATGTTTAAAAGT ATATAATAAAAATATTTAATTTTTTTTTAAATTA GCCX1CC Kozak consensus wherein X1= A or G Kozak GCCACC Kozak plus start codon GCCACCATG ATAATTCCCCCACCACCTCCCATATGTCCAGATTCTCTTGATGATGCTGATGCTTTGGGA AGTATGTTAATTTCATGGTACATGAGTGGCTATCATACTGGCTATTATATGGTAAGTAATC ACTCAGCATCTTTTCCTGACAATTTTTTTGTAGTTATGTGACTTTGTTTTGTAAATTTATAA AATACTACTTGCTTCTCTCTTTATATTACTAAAAAATAAAAATAAAAAAATACAACTGTCTG AGGCTTAAATTACTCTTGCATTGTCCCTAAGTATAATTTTAGTTAATTTTAAAAAGCTTTCA TGCTATTGTTAGATTATTTTGATTATACACTTTTGAATTGAAATTATACTTTTTCTAAATAAT GTTTTAATCTCTGATTTGAAATTGATTGTAGGGAATGGAAAAGATGGGATAATTTTTCATA AATGAAAAATGAAATTCTTTTTTTTTTTTTTTTTTTTTTGAGACGGAGTCTTGCTCTGTTGC CCAGGCTGGAGTGCAATGGCGTGATCTTGGCTCACAGCAAGCTCTGCCTCCTGGATTCA CGCCATTCTCCTGCCTCAGCCTCAGAGGTAGCTGGGACTACAGGTGCCTGCCACCACG CCTGGCTAGCTGGGATTAGAGGTCCCCACCACCATGCCTGGCTAATTTTTTGTACTTTCA GTAGAAACGGGGTTTTGCCATGTTGGCCAGGCTGTTCTCGAACTCCTGAGCTCAGGTGA SMN2ind minigene of TCCAACTGTCTCGGCCTCCCAAAGTGCTGGGATTACAGGCGTGAGCCACTGTGCCTAGC WO 2021 / 163556 A1 CTGAGCCACCACGCCGGCCTAATTTTTAAATTTTTTGTAGAGACAGGGTCTCATTATGTT (SEQ ID NO:2 of WO GCCCAGGGTGGTGTCAAGCTCCAGGTCTCAAGTGATCCCCCTACCTCCGCCTCCCAAA 2021 / 163556 A1) GTTGTGGGATTGTAGGCATGAGCCACTGCAAGAAAACCTTAACTGCAGCCTAATAATTGT TTTCTTTGGGATAACTTTTAAAGTACATTAAAAGACTATCAACTTAATTTCTGATCATATTT TGTTGAATAAAATAAGTAAAATGTCTTGTGAAACAAAATGCTTTTTAACATCCATATAAAG CTATCTATATATAGCTATCTATATCTATATAGCTATTTTTTTTAACTTCCTTTATTTTCCTTC CAGGATTTTAGACAAAATCAAAAAGAAGGAAGGTGCTCACATTCCTTAAATATAAGGAGT AAGTCTGCCAGCATTATGAAAGTGAATCTTACTTTTGTAAAACTTTATGGTTTGTGGAAAA CAAATGTTTTTGAACATTTAAAAAGTTCAGATGTTAGAAAGTTGAAAGGTTAATGTAAAAC AATCAATATTAAAGAATTTTGATGCCAAAACTATTAGATAAAAGGTTAATCTACATCCCTA CTAGAATTCTCATACTTAACTGGTTGGTTGTGTGGAAGAAACATACTTTCACAATAAAGAG CTTTAGGATATGATGCCATTTTATATCACTAGTAGGCAGACCAGCAGACTTTTTTTTATTG TGATATGGGATAACCTAGGCATACTGCACTGTACACTCTGACATATGAAGTGCTCTAGTC AAGTTTAACTGGTGTCCACAGAGGACATGGTTTAACTGGATCTGACATATGAAGTGCTCT AGTCAAGTTTAACTGGTGTCCACAGAGGACATGGTTTAACTGGAATTCGTCAAGCCTCTG GTTCTAATTTCTCATTTGCAGGAAATGCTGGCATAGAGCAGCAC ATAATTCCCCCACCACCTCCCATATGTCCAGATTCTCTTGATGATGCTGATGCTTTGGGA AGTATGTTAATTTCATGGTACATGAGTGGCTATCATACTGGCTATTATATGGTAAGTAATC ACTCAGCATCTTTTCCTGACAATTTTTTTGTAGTTATGTGACTTTGTTTTGTAAATTTATAA AATACTACTTGCTTCTCTCTTTATATTACTAAAAAATAAAAATAAAAAAATACAACTGTCTG pLS41 ON-switch AGGCTTAAATTACTCTTGCATTGTCCCTAAGTATAATTTTAGTTAATTTTAAAAAGCTTTCA CAAAATGCTTTTTAACATCCATATAAAGCTATCTATATATAGCTATCTATATCTATATAGCT ATTTTTTTTAACTTCCTTTATTTTCCTTACAGGGTTTTAGACAAAATCAAAAAGAAGGAAGG P37829 TGCTCACATTCCTTAAATATAAGGAGAAATGCTGGCATAGAGCAGCACGTAAGTCTGCCA GCATTATGAAAGTGAATCTTACTTTTGTAAAACTTTATGGTTTGTGGAAAACAAATGTTTTT GAACATTTAAAAAGTTCAGATGTTAGAAAGTTGAAAGGTTAATGTAAAACAATCAATATTA AAGAATTTTGATGCCAAAACTATTAGATAAAAGGTTAATCTACATCCCTACTAGAATTCTC ATACTTAACTGGTTGGTTGTGTGGAAGAAACATACTTTCACAATAAAGAGCTTTAGGATAT GATGCCATTTTATATCACTAGTAGGCAGACCAGCAGACTTTTTTTTATTGTGATATGGGAT AACCTAGGCATACTGCACTGTACACTCTGACATATGAAGTGCTCTAGTCAAGTTTAACTG GTGTCCACAGAGGACATGGTTTAACTGGAATTCGTCAAGCCTCTGGTTCTAATTTCTCAT TTGCAG ATAATTCCCCCACCACCTCCCATATGTCCAGATTCTCTTGATGATGCTGATGCTTTGGGA AGTATGTTAATTTCATGGTACATGAGTGGCTATCATACTGGCTATTATATGGTAAGTAATC ACTCAGCATCTTTTCCTGACAATTTTTTTGTAGTTATGTGACTTTGTTTTGTAAATTTATAA AATACTACTTGCTTCTCTCTTTATATTACTAAAAAATAAAAATAAAAAAATACAACTGTCTG AGGCTTAAATTACTCTTGCATTGTCCCTAAGTATAATTTTAGTTAATTTTAAAAAGCTTTCA TGCTATCTTAACTGCAGCCTAATAATTGTTTTCTTTGGGATAACTTTTAAAGTACATTAAAA GACTATCAACTTAATTTCTGATCATATTTTGTTGAATAAAATAAGTAAAATGTCTTGTGAAA CAAAATGCTTTTTAACATCCATATAAAGCTATCTATATATAGCTATCTATATCTATATAGCT pLS76 ON-switch ATTTTTTTTAACTTCCTTTATTTTCCTTCCAGGATTTTAGACAAAATCAAAAAGAAGGAAGG TGCTCACATTCCTTAAATATAAGGAGTAAGTCTGCCAGCATTATGAAAGTGAATCTTACTT TTGTAAAACTTTATGGTTTGTGGAAAACAAATGTTTTTGAACATTTAAAAAGTTCAGATGTT AGAAAGTTGAAAGGTTAATGTAAAACAATCAATATTAAAGAATTTTGATGCCAAAACTATT AGATAAAAGGTTAATCTACATCCCTACTAGAATTCTCATACTTAACTGGTTGGTTGTGTGG AAGAAACATACTTTCACAATAAAGAGCTTTAGGATATGATGCCATTTTATATCACTAGTAG GCAGACCAGCAGACTTTTTTTTATTGTGATATGGGATAACCTAGGCATACTGCACTGTAC ACTCTGACATATGAAGTGCTCTAGTCAAGTTTAACTGGTGTCCACAGAGGACATGGTTTA ACTGGAATTCGTCAAGCCTCTGGTTCTAATTTCTCATTTGCAGGAAATGCTGGCATAGAG CAGCAC ATAATTCCCCCACCACCTCCCATATGTCCAGATTCTCTTGATGATGCTGATGCTTTGGGA AGTATGTTAATTTCATGGTACATGAGTGGCTATCATACTGGCTATTATATGGTAAGTAATC ACTCAGCATCTTTTCCTGACAATTTTTTTGTAGTTATGTGACTTTGTTTTGTAAATTTATAA AATACTACTTGCTTCTCTCTTTATATTACTTTAAAAGACTATCAACTTAATTTCTGATCATAT TTTGTTGAATAAAATAAGTAAAATGTCTTGTGAAACAAAATGCTTTTTAACATCCATATAAA pLS159 ON-switch GCTATCTATATATAGCTATCTATATCTATATAGCTATTTTTTTTAACTTCCTTTATTTTCCTT CCAGGATTTTAGACAAAATCAAAAAGAAGGAAGGTGCTCACATTCCTTAAATATAAGGAG TAAGTCTGCCAGCATTATGAAAGTGAATCTTACTTTTGTAAAACTTTATGGTTTGTGGAAA ACAAATGTTTTTGAACATTTAAAAAGTTCAGATGTTAGAACTTTTTTTTATTGTGATATGGG ATAACCTAGGCATACTGCACTGTACACTCTGACATATGAAGTGCTCTAGTCAAGTTTAAC TGGTGTCCACAGAGGACATGGTTTAACTGGAATTCGTCAAGCCTCTGGTTCTAATTTCTC ATTTGCAGGAAATGCTGGCATAGAGCAGCAC ATAATTCCCCCACCACCTCCCATATGTCCAGATTCTCTTGATGATGCTGATGCTTTGGGA AGTATGTTAATTTCATGGTACATGAGTGGCTATCATACTGGCTATTATATGGTAAGTAATC ACTCAGCATCTTTTCCTGACAATTTTTTTGTAGTTATGTGACTTTGTTTTGTAAATTTATAA AATACGTAAAATGTCTTGTGAAACAAAATGCTTTTTAACATCCATATAAAGCTATCTATATA pLS160 ON-switch TAGCTATCTATATCTATATAGCTATTTTTTTTAACTTCCTTTATTTTCCTTCCAGGATTTTAG ACAAAATCAAAAAGAAGGAAGGTGCTCACATTCCTTAAATATAAGGAGTAAGTCTGCCAG CATTATGAAAGTGAATCTTACTTTTGTAAAACTTTATGGTTTGTGGAAAACAAATGTTTTTG AACTGACATATGAAGTGCTCTAGTCAAGTTTAACTGGTGTCCACAGAGGACATGGTTTAA CTGGAATTCGTCAAGCCTCTGGTTCTAATTTCTCATTTGCAGGAAATGCTGGCATAGAGC AGCAC GATTCTCTTGATGATGCTGATGCTTTGGGAAGTATGTTAATTTCATGGTACATGAGTGGC TATCATACTGGCTATTATATGGTAAGTAATCACTCAGCATCTTTTCCTGACAATTTTTTTGT AGTTATGTGACTTTGTTTTGTAAATTTATAAAATACTACTTGCTTCTCTCTTTATATTACTAA AAAATAAAAATAAAAAAATACAACTGTCTGAGGCTTAAATTACTCTTGCATTGTCCCTAAG TATAATTTTAGTTAATTTTAAAAAGCTTTCATGCTATCTTAACTGCAGCCTAATAATTGTTT TCTTTGGGATAACTTTTAAAGTACATTAAAAGACTATCAACTTAATTTCTGATCATATTTTG TTGAATAAAATAAGTAAAATGTCTTGTGAAACAAAATGCTTTTTAACATCCATATAAAGCTA TCTATATATAGCTATCTATATCTATATAGCTATTTTTTTTAACTTCCTTTATTTTCCTTCCAG pLS167 ON-switch GATTTTAGACAAAATCAAAAAGAAGGAAGGTGCTCACATTCCTTAAATATAAGGAGTAAG TCTGCCAGCATTATGAAAGTGAATCTTACTTTTGTAAAACTTTATGGTTTGTGGAAAACAA ATGTTTTTGAACATTTAAAAAGTTCAGATGTTAGAAAGTTGAAAGGTTAATGTAAAACAAT CAATATTAAAGAATTTTGATGCCAAAACTATTAGATAAAAGGTTAATCTACATCCCTACTA GAATTCTCATACTTAACTGGTTGGTTGTGTGGAAGAAACATACTTTCACAATAAAGAGCTT TAGGATATGATGCCATTTTATATCACTAGTAGGCAGACCAGCAGACTTTTTTTTATTGTGA TATGGGATAACCTAGGCATACTGCACTGTACACTCTGACATATGAAGTGCTCTAGTCAAG TTTAACTGGTGTCCACAGAGGACATGGTTTAACTGGAATTCGTCAAGCCTCTGGTTCTAA pLS168 ON-switch ACTCAGCATCTTTTCCTGACAATTTTTTTGTAGTTATGTGACTTTGTTTTGTAAATTTATAA AATACTACTTGCTTCTCTCTTTATATTACTAAAAAATAAAAATAAAAAAATACAACTGTCTG AGGCTTAAATTACTCTTGCATTGTCCCTAAGTATAATTTTAGTTAATTTTAAAAAGCTTTCA P37829 TGCTATCTTAACTGCAGCCTAATAATTGTTTTCTTTGGGATAACTTTTAAAGTACATTAAAA GACTATCAACTTAATTTCTGATCATATTTTGTTGAATAAAATAAGTAAAATGTCTTGTGAAA CAAAATGCTTTTTAACATCCATATAAAGCTATCTATATATAGCTATCTATATCTATATAGCT ATTTTTTTTAACTTCCTTTATTTTCCTTCCAGGATTTTAGACAAAATCAAAAAGAAGGAAGG TGCTCACATTCCTTAAATATAAGGAGTAAGTCTGCCAGCATTATGAAAGTGAATCTTACTT TTGTAAAACTTTATGGTTTGTGGAAAACAAATGTTTTTGAACATTTAAAAAGTTCAGATGTT AGAAAGTTGAAAGGTTAATGTAAAACAATCAATATTAAAGAATTTTGATGCCAAAACTATT AGATAAAAGGTTAATCTACATCCCTACTAGAATTCTCATACTTAACTGGTTGGTTGTGTGG AAGAAACATACTTTCACAATAAAGAGCTTTAGGATATGATGCCATTTTATATCACTAGTAG GCAGACCAGCAGACTTTTTTTTATTGTGATATGGGATAACCTAGGCATACTGCACTGTAC ACTCTGACATATGAAGTGCTCTAGTCAAGTTTAACTGGTGTCCACAGAGGACATGGTTTA ACTGGAATTCGTCAAGCCTCTGGTTCTAATTTCTCATTTGCAGGAAATGCTGGCATAGAG CAGCAC GCAATTTCATGGTACGGCAGTGGCTATCATACTGGCTATTATATGGTAAGTAATCACTCA GCATCTTTTCCTGACAATTTTTTTGTAGTTATGTGACTTTGTTTTGTAAATTTATAAAATAC TACTTGCTTCTCTCTTTATATTACTTTAAAAGACTATCAACTTAATTTCTGATCATATTTTGT TGAATAAAATAAGTAAAATGTCTTGTGAAACAAAATGCTTTTTAACATCCATATAAAGCTAT CTATATATAGCTATCTATATCTATATAGCTATTTTTTTTAACTTCCTTTATTTTCCTTCCAGG pLS179 ON-switch ATTTTAGACAAAATCAAAAAGAAGGAAGGTGCTCACATTCCTTAAATATAAGGAGTAAGT CTGCCAGCATTATGAAAGTGAATCTTACTTTTGTAAAACTTTATGGTTTGTGGAAAACAAA TGTTTTTGAACATTTAAAAAGTTCAGATGTTAGAACTTTTTTTTATTGTGATATGGGATAAC CTAGGCATACTGCACTGTACACTCTGACATATGAAGTGCTCTAGTCAAGTTTAACTGGTG TCCACAGAGGACATGGTTTAACTGGAATTCGTCAAGCCTCTGGTTCTAATTTCTCATTTG CAGGAAATGCTGGCATAGAGCAGCAC GCAATTTCATGGTACGGCAGTGGCTATCATACTGGCTATTATATGGTAAGTAATCACTCA GCATCTTTTCCTGACAATTTTTTTGTAGTTATGTGACTTTGTTTTGTAAATTTATAAAATAC TACTTGCTTCTCTCTTTATATTACTTTAAAAGACTATCAACTTAATTTCTGATCATATTTTGT TGAATAAAATAAGTAAAATGTCTTGTGAAACAAAATGCTTTTTAACATCCATATAAAGCTAT CTATATATAGCTATCTATATCTATATAGCTATTTTTTTTAACTTCCTTTATTTTCCTTCCAGG pMM70 ON-switch ATTTTAGACAAAATCAAAAAGAAGGAAGGTGCTCACATTCCTTAAATATAAGGAGTAAGT CTGCCAGCATTATGAAAGTGAATCTTACTTTTGTAAAACTTTATGGTTTGTGGAAAACAAA TGTTTTTGAACATTTAAAAAGTTCAGATGTTAGAACTTTTTTTTATTGTGATATGGGATAAC CTAGGCATACTGCACTGTACACTCTGACATATGAAGTGCTCTAGTCAAGTTTAACTGGTG TCCACAGAGGACATGGTTTAACTGGAATTCGTCAAGCCTCTGGTTCTAATTTCTCATTTG CAGGAAATGCTGGCATAGAG GCAATTTCATGGTACGGCAGTGGCTATCATACTGGCTATTATATGGTAAGTAATCACTCA GCATCTTTTCCTGACAATTTTTTTGTAGTTATGTGACTTTGTTTTGTAAATTTATAAAATAC TACTTGCTTCTCTCTTTATATTACTTTAAAAGACTATCAACTTAATTTCTGATCATATTTTGT TGAATAAAATAAGTAAAATGTCTTGTGAAACAAAATGCTTTTTAACATCCATATAAAGCTAT CTATATATAGCTATCTATATCTATATAGCTATTTTTTTTAACTTCCTTTATTTTCCTTCCAGG pMM71 ON-switch ATTTTAGACAAAATCAAAAAGAAGGAAGGTGCTCACATTCCTTAAATATAAGGAGTAAGT CTGCCAGCATTATGAAAGTGAATCTTACTTTTGTAAAACTTTATGGTTTGTGGAAAACAAA TGTTTTTGAACATTTAAAAAGTTCAGATGTTAGAACTTTTTTTTATTGTGATATGGGATAAC CTAGGCATACTGCACTGTACACTCTGACATATGAAGTGCTCTAGTCAAGTTTAACTGGTG TCCACAGAGGACATGGTTTAACTGGAATTCGTCAAGCCTCTGGTTCTAATTTCTCATTTG CAGGAAATGCTGGC GCAATTTCATGGTACGGCAGTGGCTATCATACTGGCTATTATATGGTAAGTAATCACTCA GCATCTTTTCCTGACAATTTTTTTGTAGTTATGTGACTTTGTTTTGTAAATTTATAAAATAC TACTTGCTTCTCTCTTTATATTACTTTAAAAGACTATCAACTTAATTTCTGATCATATTTTGT TGAATAAAATAAGTAAAATGTCTTGTGAAACAAAATGCTTTTTAACATCCATATAAAGCTAT CTATATATAGCTATCTATATCTATATAGCTATTTTTTTTAACTTCCTTTATTTTCCTTCCAGG pMM72 ON-switch ATTTTAGACAAAATCAAAAAGAAGGAAGGTGCTCACATTCCTTAAATATAAGGAGTAAGT CTGCCAGCATTATGAAAGTGAATCTTACTTTTGTAAAACTTTATGGTTTGTGGAAAACAAA TGTTTTTGAACATTTAAAAAGTTCAGATGTTAGAACTTTTTTTTATTGTGATATGGGATAAC CTAGGCATACTGCACTGTACACTCTGACATATGAAGTGCTCTAGTCAAGTTTAACTGGTG TCCACAGAGGACATGGTTTAACTGGAATTCGTCAAGCCTCTGGTTCTAATTTCTCATTTG CAGGAAATGCT GCAATTTCATGGTACGGCAGTGGCTATCATACTGGCTATTATATGGTAAGTAATCACTCA GCATCTTTTCCTGACAATTTTTTTGTAGTTATGTGACTTTGTTTTGTAAATTTATAAAATAC TACTTGCTTCTCTCTTTATATTACTTTAAAAGACTATCAACTTAATTTCTGATCATATTTTGT TGAATAAAATAAGTAAAATGTCTTGTGAAACAAAATGCTTTTTAACATCCATATAAAGCTAT CTATATATAGCTATCTATATCTATATAGCTATTTTTTTTAACTTCCTTTATTTTCCTTCCAGG pMM73 ON-switch ATTTTAGACAAAATCAAAAAGAAGGAAGGTGCTCACATTCCTTAAATATAAGGAGTAAGT CTGCCAGCATTATGAAAGTGAATCTTACTTTTGTAAAACTTTATGGTTTGTGGAAAACAAA TGTTTTTGAACATTTAAAAAGTTCAGATGTTAGAACTTTTTTTTATTGTGATATGGGATAAC CAGGAAAT pMM143 ON-switch GCAATTTCATGGTACGGCAGTGGCTATCATACTGGCTATTATATGGTAAGTAATCACTCA P37829 GCATCTTTTCCTGACAATTTTTTTGTAGTTATGTGACTTTGTTTTGTAAATTTATAAAATAC TACTTGCTTCTCTCTTTATATTACTTTAAAAGACTATCAACTTAATTTCTGATCATATTTTGT TGAATAAAATAAGTAAAATGTCTTGTGAAACAAAATGCTTTTTAACATCCATATAAAGCTAT CTATATATAGCTATCTATATCTATATAGCTATTTTTTTTAACTTCCTTTATTTTCCTTCCAGG ATTTTAGACAAAATCAAAAAGAAGGAAGGTGCTCACATTCCTTAAATATAAGGAGTAAGT CTGCTCCTCTTATGAAAGTGAATCTTACTTTTGTAAAACTTTATGGTTTGTGGAAAACAAA TGTTTTTGAACATTTAAAAAGTTCAGATGTTAGAACTTTTTTTTATTGTGATATGGGATAAC CTAGGCATACTGCACTGTACACTCTGACATATGAAGTGCTCTAGTCAAGTTTAACTGGTG TCCACAGAGGACATGGTTTAACTGGAATTCGTCAAGCCTCTGGTTCTAATTTCTCATTTG CAGGAAATGCTGGCATAGAGCAGCAC GCAATTTCATGGTACGGCAGTGGCTATCATACTGGCTATTATATGGTAAGTAATCACTCA GCATCTTTTCCTGACAATTTTTTTGTAGTTATGTGACTTTGTTTTGTAAATTTATAAAATAC TACTTGCTTCTCTCTTTATATTACTTTAAAAGACTATCAACTTAATTTCTGATCATATTTTGT TGAATAAAATAAGTAAAATGTCTTGTGAAACAAAATGCTTTTTAACATCCATATAAAGCTAT CTATATATAGCTATCTATATCTATATAGCTATTTTTTTTAACTTCCTTTATTTTCCTTCCAGG pMM144 ON-switch ATTTTAGACAAAATCAAAAAGAAGGAAGGTGCTCACATTCCTTAAATATAAGGAGTAAGT CTGCAAGGCTTATGAAAGTGAATCTTACTTTTGTAAAACTTTATGGTTTGTGGAAAACAAA TGTTTTTGAACATTTAAAAAGTTCAGATGTTAGAACTTTTTTTTATTGTGATATGGGATAAC CTAGGCATACTGCACTGTACACTCTGACATATGAAGTGCTCTAGTCAAGTTTAACTGGTG TCCACAGAGGACATGGTTTAACTGGAATTCGTCAAGCCTCTGGTTCTAATTTCTCATTTG CAGGAAATGCTGGCATAGAGCAGCAC GCAATTTCATGGTACGGCAGTGGCTATCATACTGGCTATTATATGGTAAGTAATCACTCA GCATCTTTTCCTGACAATTTTTTTGTAGTTATGTGACTTTGTTTTGTAAATTTATAAAATAC TACTTGCTTCTCTCTTTATATTACTTTAAAAGACTATCAACTTAATTTCTGATCATATTTTGT TGAATAAAATAAGTAAAATGTCTTGTGAAACAAAATGCTTTTTAACATCCATATAAAGCTAT CTATATATAGCTATCTATATCTATATAGCTATTTTTTTTAACTTCCTTTATTTTCCTTCCAGG pMM145 ON-switch ATTTTAGACAAAATCAAAAAGAAGGAAGGTGCTCACATTCCTTAAATATAAGGAGTAAGT CTGCTAGTCTTATGAAAGTGAATCTTACTTTTGTAAAACTTTATGGTTTGTGGAAAACAAA TGTTTTTGAACATTTAAAAAGTTCAGATGTTAGAACTTTTTTTTATTGTGATATGGGATAAC CTAGGCATACTGCACTGTACACTCTGACATATGAAGTGCTCTAGTCAAGTTTAACTGGTG TCCACAGAGGACATGGTTTAACTGGAATTCGTCAAGCCTCTGGTTCTAATTTCTCATTTG CAGGAAATGCTGGCATAGAGCAGCAC GCAATTTCATGGTACGGCAGTGGCTATCATACTGGCTATTATATGGTAAGTAATCACTCA GCATCTTTTCCTGACAATTTTTTTGTAGTTATGTGACTTTGTTTTGTAAATTTATAAAATAC TACTTGCTTCTCTCTTTATATTACTTTAAAAGACTATCAACTTAATTTCTGATCATATTTTGT TGAATAAAATAAGTAAAATGTCTTGTGAAACAAAATGCTTTTTAACATCCATATAAAGCTAT CTATATATAGCTATCTATATCTATATAGCTATTTTTTTTAACTTCCTTTATTTTCCTTCCAGG pMM146 ON-switch ATTTTAGACAAAATCAAAAAGAAGGAAGGTGCTCACATTCCTTAAATATAAGGAGTAAGT CTGCTTTCAGCATTATGAAAGTGAATCTTACTTTTGTAAAACTTTATGGTTTGTGGAAAAC AAATGTTTTTGAACATTTAAAAAGTTCAGATGTTAGAACTTTTTTTTATTGTGATATGGGAT AACCTAGGCATACTGCACTGTACACTCTGACATATGAAGTGCTCTAGTCAAGTTTAACTG GTGTCCACAGAGGACATGGTTTAACTGGAATTCGTCAAGCCTCTGGTTCTAATTTCTCAT TTGCAGGAAATGCTGGCATAGAGCAGCAC GCAATTTCATGGTACGGCAGTGGCTATCATACTGGCTATTATATGGTAAGTAATCACTCA GCATCTTTTCCTGACAATTTTTTTGTAGTTATGTGACTTTGTTTTGTAAATTTATAAAATAC TACTTGCTTCTCTCTTTATATTACTTTAAAAGACTATCAACTTAATTTCTGATCATATTTTGT TGAATAAAATAAGTAAAATGTCTTGTGAAACAAAATGCTTTTTAACATCCATATAAAGCTAT CTATATATAGCTATCTATATCTATATAGCTATTTTTTTTAACTTCCTTTATTTTCCTTCCAGG pMM147 ON-switch ATTTTAGACAAAATCAAAAAGAAGGAAGGTGCTCACATTCCTTAAATATAAGGAGTAAGT CTGCCCCCAGCATTATGAAAGTGAATCTTACTTTTGTAAAACTTTATGGTTTGTGGAAAAC AAATGTTTTTGAACATTTAAAAAGTTCAGATGTTAGAACTTTTTTTTATTGTGATATGGGAT AACCTAGGCATACTGCACTGTACACTCTGACATATGAAGTGCTCTAGTCAAGTTTAACTG GTGTCCACAGAGGACATGGTTTAACTGGAATTCGTCAAGCCTCTGGTTCTAATTTCTCAT TTGCAGGAAATGCTGGCATAGAGCAGCAC GCAATTTCATGGTACGGCAGTGGCTATCATACTGGCTATTATATGGTAAGTAATCACTCA GCATCTTTTCCTGACAATTTTTTTGTAGTTATGTGACTTTGTTTTGTAAATTTATAAAATAC TACTTGCTTCTCTCTTTATATTACTTTAAAAGACTATCAACTTAATTTCTGATCATATTTTGT TGAATAAAATAAGTAAAATGTCTTGTGAAACAAAATGCTTTTTAACATCCATATAAAGCTAT CTATATATAGCTATCTATATCTATATAGCTATTTTTTTTAACTTCCTTTATTTTCCTTCCAGG pMM136 ON-switch ATTTTAGACAAAATCAAAAAGAAGGTAGGTGCTCACATTCCTTAAATATAAGGAGTAAGTC TGCCAGCATTATGAAAGTGAATCTTACTTTTGTAAAACTTTATGGTTTGTGGAAAACAAAT GTTTTTGAACATTTAAAAAGTTCAGATGTTAGAACTTTTTTTTATTGTGATATGGGATAACC TAGGCATACTGCACTGTACACTCTGACATATGAAGTGCTCTAGTCAAGTTTAACTGGTGT CCACAGAGGACATGGTTTAACTGGAATTCGTCAAGCCTCTGGTTCTAATTTCTCATTTGC AGGAAATGCTGGCATAGAGCAGCAC pMM137 ON-switch TACTTGCTTCTCTCTTTATATTACTTTAAAAGACTATCAACTTAATTTCTGATCATATTTTGT TGAATAAAATAAGTAAAATGTCTTGTGAAACAAAATGCTTTTTAACATCCATATAAAGCTAT P37829 CTATATATAGCTATCTATATCTATATAGCTATTTTTTTTAACTTCCTTTATTTTCCTTCCAGG ATTTTAGACAAAATCAAAAAGAAGGATGGTGCTCACATTCCTTAAATATAAGGAGTAAGTC TGCCAGCATTATGAAAGTGAATCTTACTTTTGTAAAACTTTATGGTTTGTGGAAAACAAAT GTTTTTGAACATTTAAAAAGTTCAGATGTTAGAACTTTTTTTTATTGTGATATGGGATAACC TAGGCATACTGCACTGTACACTCTGACATATGAAGTGCTCTAGTCAAGTTTAACTGGTGT CCACAGAGGACATGGTTTAACTGGAATTCGTCAAGCCTCTGGTTCTAATTTCTCATTTGC AGGAAATGCTGGCATAGAGCAGCAC GCAATTTCATGGTACGGCAGTGGCTATCATACTGGCTATTATATGGTAAGTAATCACTCA GCATCTTTTCCTGACAATTTTTTTGTAGTTATGTGACTTTGTTTTGTAAATTTATAAAATAC TACTTGCTTCTCTCTTTATATTACTTTAAAAGACTATCAACTTAATTTCTGATCATATTTTGT TGAATAAAATAAGTAAAATGTCTTGTGAAACAAAATGCTTTTTAACATCCATATAAAGCTAT CTATATATAGCTATCTATATCTATATAGCTATTTTTTTTAACTTCCTTTATTTTCCTTCCAGG pMM138 ON-switch ATTTTAGACAAAATCAAAAGGAAGGAAGGTGCTCACATTCCTTAAATATAAGGAGTAAGT CTGCCAGCATTATGAAAGTGAATCTTACTTTTGTAAAACTTTATGGTTTGTGGAAAACAAA TGTTTTTGAACATTTAAAAAGTTCAGATGTTAGAACTTTTTTTTATTGTGATATGGGATAAC CTAGGCATACTGCACTGTACACTCTGACATATGAAGTGCTCTAGTCAAGTTTAACTGGTG TCCACAGAGGACATGGTTTAACTGGAATTCGTCAAGCCTCTGGTTCTAATTTCTCATTTG CAGGAAATGCTGGCATAGAGCAGCAC GCAATTTCATGGTACGGCAGTGGCTATCATACTGGCTATTATATGGTAAGTAATCACTCA GCATCTTTTCCTGACAATTTTTTTGTAGTTATGTGACTTTGTTTTGTAAATTTATAAAATAC TACTTGCTTCTCTCTTTATATTACTTTAAAAGACTATCAACTTAATTTCTGATCATATTTTGT TGAATAAAATAAGTAAAATGTCTTGTGAAACAAAATGCTTTTTAACATCCATATAAAGCTAT CTATATATAGCTATCTATATCTATATAGCTATTTTTTTTAACTTCCTTTATTTTCCTTCCAGG pMM139 ON-switch ATTTTAGACAAAATCAAAAAGAAGGAAAGTGCTCACATTCCTTAAATATAAGGAGTAAGTC TGCCAGCATTATGAAAGTGAATCTTACTTTTGTAAAACTTTATGGTTTGTGGAAAACAAAT GTTTTTGAACATTTAAAAAGTTCAGATGTTAGAACTTTTTTTTATTGTGATATGGGATAACC TAGGCATACTGCACTGTACACTCTGACATATGAAGTGCTCTAGTCAAGTTTAACTGGTGT CCACAGAGGACATGGTTTAACTGGAATTCGTCAAGCCTCTGGTTCTAATTTCTCATTTGC AGGAAATGCTGGCATAGAGCAGCAC GCAATTTCATGGTACGGCAGTGGCTATCATACTGGCTATTATATGGTAAGTAATCACTCA GCATCTTTTCCTGACAATTTTTTTGTAGTTATGTGACTTTGTTTTGTAAATTTATAAAATAC TACTTGCTTCTCTCTTTATATTACTTTAAAAGACTATCAACTTAATTTCTGATCATATTTTGT TGAATAAAATAAGTAAAATGTCTTGTGAAACAAAATGCTTTTTAACATCCATATAAAGCTAT CTATATATAGCTATCTATATCTATATAGCTATTTTTTTTAACTTCCTTTATTTTCCTTCCAGG pMM140 ON-switch ATTTTAGACAAAATCAAAATGAAGGAAGGTGCTCACATTCCTTAAATATAAGGAGTAAGTC TGCCAGCATTATGAAAGTGAATCTTACTTTTGTAAAACTTTATGGTTTGTGGAAAACAAAT GTTTTTGAACATTTAAAAAGTTCAGATGTTAGAACTTTTTTTTATTGTGATATGGGATAACC TAGGCATACTGCACTGTACACTCTGACATATGAAGTGCTCTAGTCAAGTTTAACTGGTGT CCACAGAGGACATGGTTTAACTGGAATTCGTCAAGCCTCTGGTTCTAATTTCTCATTTGC AGGAAATGCTGGCATAGAGCAGCAC GCAATTTCATGGTACGGCAGTGGCTATCATACTGGCTATTATATGGTAAGTAATCACTCA GCATCTTTTCCTGACAATTTTTTTGTAGTTATGTGACTTTGTTTTGTAAATTTATAAAATAC TACTTGCTTCTCTCTTTATATTACTTTAAAAGACTATCAACTTAATTTCTGATCATATTTTGT TGAATAAAATAAGTAAAATGTCTTGTGAAACAAAATGCTTTTTAACATCCATATAAAGCTAT CTATATATAGCTATCTATATCTATATAGCTATTTTTTTTAACTTCCTTTATTTTCCTTCCAGG pMM141 ON-switch ATTTTAGACAAAATCAAAAAGAGGGAAGGTGCTCACATTCCTTAAATATAAGGAGTAAGT CTGCCAGCATTATGAAAGTGAATCTTACTTTTGTAAAACTTTATGGTTTGTGGAAAACAAA TGTTTTTGAACATTTAAAAAGTTCAGATGTTAGAACTTTTTTTTATTGTGATATGGGATAAC CTAGGCATACTGCACTGTACACTCTGACATATGAAGTGCTCTAGTCAAGTTTAACTGGTG TCCACAGAGGACATGGTTTAACTGGAATTCGTCAAGCCTCTGGTTCTAATTTCTCATTTG CAGGAAATGCTGGCATAGAGCAGCAC GCAATTTCATGGTACGGCAGTGGCTATCATACTGGCTATTATATGGTAAGTAATCACTCA GCATCTTTTCCTGACAATTTTTTTGTAGTTATGTGACTTTGTTTTGTAAATTTATAAAATAC TACTTGCTTCTCTCTTTATATTACTTTAAAAGACTATCAACTTAATTTCTGATCATATTTTGT TGAATAAAATAAGTAAAATGTCTTGTGAAACAAAATGCTTTTTAACATCCATATAAAGCTAT CTATATATAGCTATCTATATCTATATAGCTATTTTTTTTAACTTCCTTTATTTTCCTTCCAGG pMM142 ON-switch ATTTTAGACAAAATCAAAAAGAAGGAAGGAGCACACATTCCTTAAATATAAGGAGTAAGT CTGCCAGCATTATGAAAGTGAATCTTACTTTTGTAAAACTTTATGGTTTGTGGAAAACAAA TGTTTTTGAACATTTAAAAAGTTCAGATGTTAGAACTTTTTTTTATTGTGATATGGGATAAC CTAGGCATACTGCACTGTACACTCTGACATATGAAGTGCTCTAGTCAAGTTTAACTGGTG TCCACAGAGGACATGGTTTAACTGGAATTCGTCAAGCCTCTGGTTCTAATTTCTCATTTG CAGGAAATGCTGGCATAGAGCAGCAC GCAATTTCATGGTACGGCAGTGGCTATCATACTGGCTATTATATGGTAAGTAATCACTCA GCATCTTTTCCTGACAATTTTTTTGTAGTTATGTGACTTTGTTTTGTAAATTTATAAAATAC TACTTGCTTCTCTCTTTATATTACTTTAAAAGACTATCAACTTAATTTCTGATCATATTTTGT pMM151 ON-switch ATTTTAGAGAAGGAAGGTGCTCACATTCCTTAAATATAAGGAGTAAGTCTGCCAGCATTA TGAAAGTGAATCTTACTTTTGTAAAACTTTATGGTTTGTGGAAAACAAATGTTTTTGAACAT TTAAAAAGTTCAGATGTTAGAACTTTTTTTTATTGTGATATGGGATAACCTAGGCATACTG CACTGTACACTCTGACATATGAAGTGCTCTAGTCAAGTTTAACTGGTGTCCACAGAGGAC ATGGTTTAACTGGAATTCGTCAAGCCTCTGGTTCTAATTTCTCATTTGCAGGAAATGCTG GCATAGAGCAGCAC GCAATTTCATGGTACGGCAGTGGCTATCATACTGGCTATTATATGGTAAGTAATCACTCA GCATCTTTTCCTGACAATTTTTTTGTAGTTATGTGACTTTGTTTTGTAAATTTATAAAATAC TACTTGCTTCTCTCTTTATATTACTTTAAAAGACTATCAACTTAATTTCTGATCATATTTTGT TGAATAAAATAAGTAAAATGTCTTGTGAAACAAAATGCTTTTTAACATCCATATAAAGCTAT CTATATATAGCTATCTATATCTATATAGCTATTTTTTTTAACTTCCTTTATTTTCCTTCCAGG pMM152 ON-switch ATTTTAGAGAAGGAAGGTGCTTAAATATAAGGAGTAAGTCTGCCAGCATTATGAAAGTGA ATCTTACTTTTGTAAAACTTTATGGTTTGTGGAAAACAAATGTTTTTGAACATTTAAAAAGT TCAGATGTTAGAACTTTTTTTTATTGTGATATGGGATAACCTAGGCATACTGCACTGTACA CTCTGACATATGAAGTGCTCTAGTCAAGTTTAACTGGTGTCCACAGAGGACATGGTTTAA CTGGAATTCGTCAAGCCTCTGGTTCTAATTTCTCATTTGCAGGAAATGCTGGCATAGAGC AGCAC ATAATTCCCCCACCACCTCCCATATGTCCAGATTCTCTTGATGATGCTGATGCTTTGGGA AGTGGCTTAATTTCATGGTACGGCAGTGGCTATCATACTGGCTATTATCTGGTAAGTAAT CACTCAGCATCTTTTCCTGACAATTTTTTTGTAGTTATGTGACTTTGTTTTGTAAATTTATA AAATACTACTTGCTTCTCTCTTTATATTACTAAAAAATAAAAATAAAAAAATACAACTGTCT GAGGCTTAAATTACTCTTGCATTGTCCCTAAGTATAATTTTAGTTAATTTTAAAAAGCTTTC ATGCTATCTTAACTGCAGCCTAATAATTGTTTTCTTTGGGATAACTTTTAAAGTACATTAAA AGACTATCAACTTAATTTCTGATCATATTTTGTTGAATAAAATAAGTAAAATGTCTTGTGAA ACAAAATGCTTTTTAACATCCATATAAAGCTATCTATATATAGCTATCTATATCTATATAGC pLS174 ON-switch TATTTTTTTTAACTTCCTTTATTTTCCTTCCAGGATTTTAGACAAAATCAAAAAGAAGGAAG GTGCTCACATTCCTTAAATATAAGGAGTAAGTCTGCCAGCATTATGAAAGTGAATCTTACT TTTGTAAAACTTTATGGTTTGTGGAAAACAAATGTTTTTGAACATTTAAAAAGTTCAGATGT TAGAAAGTTGAAAGGTTAATGTAAAACAATCAATATTAAAGAATTTTGATGCCAAAACTAT TAGATAAAAGGTTAATCTACATCCCTACTAGAATTCTCATACTTAACTGGTTGGTTGTGTG GAAGAAACATACTTTCACAATAAAGAGCTTTAGGATATGATGCCATTTTATATCACTAGTA GGCAGACCAGCAGACTTTTTTTTATTGTGATATGGGATAACCTAGGCATACTGCACTGTA CACTCTGACATATGAAGTGCTCTAGTCAAGTTTAACTGGTGTCCACAGAGGACATGGTTT AACTGGAATTCGTCAAGCCTCTGGTTCTAATTTCTCATTTGCAGGAAATGCTGGCATAGA GCAGCAC ATAATTCCCCCACCACCTCCCATATGTCCAGATTCTCTTGATGATGCTGATGCTTTGGGA AGTGGCTTAATTTCATGGTACGGCAGTGGCTATCATACTGGCTATTATCTGGTAAGTAAT CACTCAGCATCTTTTCCTGACAATTTTTTTGTAGTTATGTGACTTTGTTTTGTAAATTTATA AAATACTACTTGCTTCTCTCTTTATATTACTAAAAAATAAAAATAAAAAAATACAACTGTCT GAGGCTTAAATTACTCTTGCATTGTCCCTAAGTATAATTTTAGTTAATTTTAAAAAGCTTTC ATGCTATCTTAACTGCAGCCTAATAATTGTTTTCTTTGGGATAACTTTTAAAGTACATTAAA AGACTATCAACTTAATTTCTGATCATATTTTGTTGAATAAAATAAGTAAAATGTCTTGTGAA ACAAAATGCTTTTTAACATCCATATAAAGCTATCTATATATAGCTATCTATATCTATATAGC pMM56 ON-switch TATTTTTTTTAACTTCCTTTATTTTCCTTCCAGGATTTTAGACAAAATCAAAAAGAAGGAAG GTGCCACCATGTCCTTAAATATAAGGAGTAAGTCTGCCAGCATTATGAAAGTGAATCTTA CTTTTGTAAAACTTTATGGTTTGTGGAAAACAAATGTTTTTGAACATTTAAAAAGTTCAGAT GTTAGAAAGTTGAAAGGTTAATGTAAAACAATCAATATTAAAGAATTTTGATGCCAAAACT ATTAGATAAAAGGTTAATCTACATCCCTACTAGAATTCTCATACTTAACTGGTTGGTTGTG TGGAAGAAACATACTTTCACAATAAAGAGCTTTAGGATATGATGCCATTTTATATCACTAG TAGGCAGACCAGCAGACTTTTTTTTATTGTGATATGGGATAACCTAGGCATACTGCACTG TACACTCTGACATATGAAGTGCTCTAGTCAAGTTTAACTGGTGTCCACAGAGGACATGGT TTAACTGGAATTCGTCAAGCCTCTGGTTCTAATTTCTCATTTGCAGGAAATGCTGGCATA GAGCAGCAC ATAATTCCCCCACCACCTCCCATATGTCCAGATTCTCTTGATGATGCTGATGCTTTGGGA AGTGGCTTAATTTCATGGTACGGCAGTGGCTATCATACTGGCTATTATCTGGTAAGTAAT CACTCAGCATCTTTTCCTGACAATTTTTTTGTAGTTATGTGACTTTGTTTTGTAAATTTATA AAATACTACTTGCTTCTCTCTTTATATTACTAAAAAATAAAAATAAAAAAATACAACTGTCT GAGGCTTAAATTACTCTTGCATTGTCCCTAAGTATAATTTTAGTTAATTTTAAAAAGCTTTC ATGCTATCTTAACTGCAGCCTAATAATTGTTTTCTTTGGGATAACTTTTAAAGTACATTAAA AGACTATCAACTTAATTTCTGATCATATTTTGTTGAATAAAATAAGTAAAATGTCTTGTGAA ACAAAATGCTTTTTAACATCCATATAAAGCTATCTATATATAGCTATCTATATCTATATAGC pMM60 ON-switch TATTTTTTTTAACTTCCTTTATTTTCCTTCCAGGATTTTAGACAAAATCAAAAAGAAGGAAG GTGCTCACATTCCTTAAGCCACCATGATAAGGAGTAAGTCTGCCAGCATTATGAAAGTGA ATCTTACTTTTGTAAAACTTTATGGTTTGTGGAAAACAAATGTTTTTGAACATTTAAAAAGT TCAGATGTTAGAAAGTTGAAAGGTTAATGTAAAACAATCAATATTAAAGAATTTTGATGCC AAAACTATTAGATAAAAGGTTAATCTACATCCCTACTAGAATTCTCATACTTAACTGGTTG GTTGTGTGGAAGAAACATACTTTCACAATAAAGAGCTTTAGGATATGATGCCATTTTATAT CATGGTTTAACTGGAATTCGTCAAGCCTCTGGTTCTAATTTCTCATTTGCAGGAAATGCT GGCATAGAGCAGCAC pMM61 ON-switch ATAATTCCCCCACCACCTCCCATATGTCCAGATTCTCTTGATGATGCTGATGCTTTGGGA AGTGGCTTAATTTCATGGTACGGCAGTGGCTATCATACTGGCTATTATCTGGTAAGTAAT CACTCAGCATCTTTTCCTGACAATTTTTTTGTAGTTATGTGACTTTGTTTTGTAAATTTATA AAATACTACTTGCTTCTCTCTTTATATTACTAAAAAATAAAAATAAAAAAATACAACTGTCT GAGGCTTAAATTACTCTTGCATTGTCCCTAAGTATAATTTTAGTTAATTTTAAAAAGCTTTC ATGCTATCTTAACTGCAGCCTAATAATTGTTTTCTTTGGGATAACTTTTAAAGTACATTAAA AGACTATCAACTTAATTTCTGATCATATTTTGTTGAATAAAATAAGTAAAATGTCTTGTGAA ACAAAATGCTTTTTAACATCCATATAAAGCTATCTATATATAGCTATCTATATCTATATAGC TATTTTTTTTAACTTCCTTTATTTTCCTTCCAGGATTTTAGACAAAATCAAAAAGAAGGAAG GTGCTCACATTCCTTAAACAACATGGAGTAAGTCTGCCAGCATTATGAAAGTGAATCTTA CTTTTGTAAAACTTTATGGTTTGTGGAAAACAAATGTTTTTGAACATTTAAAAAGTTCAGAT GTTAGAAAGTTGAAAGGTTAATGTAAAACAATCAATATTAAAGAATTTTGATGCCAAAACT ATTAGATAAAAGGTTAATCTACATCCCTACTAGAATTCTCATACTTAACTGGTTGGTTGTG TGGAAGAAACATACTTTCACAATAAAGAGCTTTAGGATATGATGCCATTTTATATCACTAG TAGGCAGACCAGCAGACTTTTTTTTATTGTGATATGGGATAACCTAGGCATACTGCACTG TACACTCTGACATATGAAGTGCTCTAGTCAAGTTTAACTGGTGTCCACAGAGGACATGGT TTAACTGGAATTCGTCAAGCCTCTGGTTCTAATTTCTCATTTGCAGGAAATGCTGGCATA GAGCAGCAC ATAATTCCCCCACCACCTCCCATATGTCCAGATTCTCTTGATGATGCTGATGCTTTGGGA AGTGGCTTAATTTCATGGTACGGCAGTGGCTATCATACTGGCTATTATCTGGTAAGTAAT CACTCAGCATCTTTTCCTGACAATTTTTTTGTAGTTATGTGACTTTGTTTTGTAAATTTATA AAATACTACTTGCTTCTCTCTTTATATTACTAAAAAATAAAAATAAAAAAATACAACTGTCT GAGGCTTAAATTACTCTTGCATTGTCCCTAAGTATAATTTTAGTTAATTTTAAAAAGCTTTC ATGCTATCTTAACTGCAGCCTAATAATTGTTTTCTTTGGGATAACTTTTAAAGTACATTAAA AGACTATCAACTTAATTTCTGATCATATTTTGTTGAATAAAATAAGTAAAATGTCTTGTGAA ACAAAATGCTTTTTAACATCCATATAAAGCTATCTATATATAGCTATCTATATCTATATAGC pMM62 ON-switch TATTTTTTTTAACTTCCTTTATTTTCCTTCCAGGATTTTAGACAAAATCAAAAAGAAGGAAG GTGCTCACATTCCTTAGCCACCATGGAGTAAGTCTGCCAGCATTATGAAAGTGAATCTTA CTTTTGTAAAACTTTATGGTTTGTGGAAAACAAATGTTTTTGAACATTTAAAAAGTTCAGAT GTTAGAAAGTTGAAAGGTTAATGTAAAACAATCAATATTAAAGAATTTTGATGCCAAAACT ATTAGATAAAAGGTTAATCTACATCCCTACTAGAATTCTCATACTTAACTGGTTGGTTGTG TGGAAGAAACATACTTTCACAATAAAGAGCTTTAGGATATGATGCCATTTTATATCACTAG TAGGCAGACCAGCAGACTTTTTTTTATTGTGATATGGGATAACCTAGGCATACTGCACTG TACACTCTGACATATGAAGTGCTCTAGTCAAGTTTAACTGGTGTCCACAGAGGACATGGT TTAACTGGAATTCGTCAAGCCTCTGGTTCTAATTTCTCATTTGCAGGAAATGCTGGCATA GAGCAGCAC ATAATTCCCCCACCACCTCCCATATGTCCAGATTCTCTTGATGATGCTGATGCTTTGGGA AGTGGCTTAATTTCATGGTACGGCAGTGGCTATCATACTGGCTATTATCTGGTAAGTAAT CACTCAGCATCTTTTCCTGACAATTTTTTTGTAGTTATGTGACTTTGTTTTGTAAATTTATA AAATACTACTTGCTTCTCTCTTTATATTACTAAAAAATAAAAATAAAAAAATACAACTGTCT GAGGCTTAAATTACTCTTGCATTGTCCCTAAGTATAATTTTAGTTAATTTTAAAAAGCTTTC ATGCTATCTTAACTGCAGCCTAATAATTGTTTTCTTTGGGATAACTTTTAAAGTACATTAAA AGACTATCAACTTAATTTCTGATCATATTTTGTTGAATAAAATAAGTAAAATGTCTTGTGAA ACAAAATGCTTTTTAACATCCATATAAAGCTATCTATATATAGCTATCTATATCTATATAGC pMM63 ON-switch TATTTTTTTTAACTTCCTTTATTTTCCTTCCAGGATTTTAGACAAAATCAAAAAGAAGGAAG GTGCTCACAGCCACCATGAATATAAGGAGTAAGTCTGCCAGCATTATGAAAGTGAATCTT ACTTTTGTAAAACTTTATGGTTTGTGGAAAACAAATGTTTTTGAACATTTAAAAAGTTCAGA TGTTAGAAAGTTGAAAGGTTAATGTAAAACAATCAATATTAAAGAATTTTGATGCCAAAAC TATTAGATAAAAGGTTAATCTACATCCCTACTAGAATTCTCATACTTAACTGGTTGGTTGT GTGGAAGAAACATACTTTCACAATAAAGAGCTTTAGGATATGATGCCATTTTATATCACTA GTAGGCAGACCAGCAGACTTTTTTTTATTGTGATATGGGATAACCTAGGCATACTGCACT GTACACTCTGACATATGAAGTGCTCTAGTCAAGTTTAACTGGTGTCCACAGAGGACATGG TTTAACTGGAATTCGTCAAGCCTCTGGTTCTAATTTCTCATTTGCAGGAAATGCTGGCATA GAGCAGCAC ATAATTCCCCCACCACCTCCCATATGTCCAGATTCTCTTGATGATGCTGATGCTTTGGGA AGTGGCTTAATTTCATGGTACGGCAGTGGCTATCATACTGGCTATTATATGGTAAGTAAT CACTCAGCATCTTTTCCTGACAATTTTTTTGTAGTTATGTGACTTTGTTTTGTAAATTTATA AAATACTACTTGCTTCTCTCTTTATATTACTAAAAAATAAAAATAAAAAAATACAACTGTCT GAGGCTTAAATTACTCTTGCATTGTCCCTAAGTATAATTTTAGTTAATTTTAAAAAGCTTTC ATGCTATCTTAACTGCAGCCTAATAATTGTTTTCTTTGGGATAACTTTTAAAGTACATTAAA AGACTATCAACTTAATTTCTGATCATATTTTGTTGAATAAAATAAGTAAAATGTCTTGTGAA ACAAAATGCTTTTTAACATCCATATAAAGCTATCTATATATAGCTATCTATATCTATATAGC pLS176 ON-switch TATTTTTTTTAACTTCCTTTATTTTCCTTCCAGGATTTTGCCACCATGCAAAATCAAAAAGA AGGAAGGTGCTCACATTCCTTAAATATAAGGAGTAAGTCTGCCAGCATTATGAAAGTGAA TCTTACTTTTGTAAAACTTTATGGTTTGTGGAAAACAAATGTTTTTGAACATTTAAAAAGTT CAGATGTTAGAAAGTTGAAAGGTTAATGTAAAACAATCAATATTAAAGAATTTTGATGCCA AAACTATTAGATAAAAGGTTAATCTACATCCCTACTAGAATTCTCATACTTAACTGGTTGG TTGTGTGGAAGAAACATACTTTCACAATAAAGAGCTTTAGGATATGATGCCATTTTATATC ACTAGTAGGCAGACCAGCAGACTTTTTTTTATTGTGATATGGGATAACCTAGGCATACTG CACTGTACACTCTGACATATGAAGTGCTCTAGTCAAGTTTAACTGGTGTCCACAGAGGAC ATGGTTTAACTGGAATTCGTCAAGCCTCTGGTTCTAATTTCTCATTTGCAGGAAATGCTG P37829 GCATAGAGCAGCAC ATAATTCCCCCACCACCTCCCATATGTCCAGATTCTCTTGATGATGCTGATGCTTTGGGA AGTGGCTTAATTTCATGGTACGGCAGTGGCTATCATACTGGCTATTATCAGGTAAGTAAT CACTCAGCATCTTTTCCTGACAATTTTTTTGTAGTTATGTGACTTTGTTTTGTAAATTTATA AAATACTACTTGCTTCTCTCTTTATATTACTAAAAAATAAAAATAAAAAAATACAACTGTCT GAGGCTTAAATTACTCTTGCATTGTCCCTAAGTATAATTTTAGTTAATTTTAAAAAGCTTTC ATGCTATCTTAACTGCAGCCTAATAATTGTTTTCTTTGGGATAACTTTTAAAGTACATTAAA AGACTATCAACTTAATTTCTGATCATATTTTGTTGAATAAAATAAGTAAAATGTCTTGTGAA ACAAAATGCTTTTTAACATCCATATAAAGCTATCTATATATAGCTATCTATATCTATATAGC pMM108 ON-switch TATTTTTTTTAACTTCCTTTATTTTCCTTCCAGGATTTTGCCACCATGCAAAATCAAAAAGA AGGAAGGTGCTCACATTCCTTAAATATAAGGAGTAAGTCTGCCAGCATTATGAAAGTGAA TCTTACTTTTGTAAAACTTTATGGTTTGTGGAAAACAAATGTTTTTGAACATTTAAAAAGTT CAGATGTTAGAAAGTTGAAAGGTTAATGTAAAACAATCAATATTAAAGAATTTTGATGCCA AAACTATTAGATAAAAGGTTAATCTACATCCCTACTAGAATTCTCATACTTAACTGGTTGG TTGTGTGGAAGAAACATACTTTCACAATAAAGAGCTTTAGGATATGATGCCATTTTATATC ACTAGTAGGCAGACCAGCAGACTTTTTTTTATTGTGATATGGGATAACCTAGGCATACTG CACTGTACACTCTGACATATGAAGTGCTCTAGTCAAGTTTAACTGGTGTCCACAGAGGAC ATGGTTTAACTGGAATTCGTCAAGCCTCTGGTTCTAATTTCTCATTTGCAGGAAATGCTG GCATAGAGCAGCAC ATAATTCCCCCACCACCTCCCATATGTCCAGATTCTCTTGATGATGCTGATGCTTTGGGA AGTGGCTTAATTTCATGGTACGGCAGTGGCTATCATACTGGCTATTATGTGGTAAGTAAT CACTCAGCATCTTTTCCTGACAATTTTTTTGTAGTTATGTGACTTTGTTTTGTAAATTTATA AAATACTACTTGCTTCTCTCTTTATATTACTAAAAAATAAAAATAAAAAAATACAACTGTCT GAGGCTTAAATTACTCTTGCATTGTCCCTAAGTATAATTTTAGTTAATTTTAAAAAGCTTTC ATGCTATCTTAACTGCAGCCTAATAATTGTTTTCTTTGGGATAACTTTTAAAGTACATTAAA AGACTATCAACTTAATTTCTGATCATATTTTGTTGAATAAAATAAGTAAAATGTCTTGTGAA ACAAAATGCTTTTTAACATCCATATAAAGCTATCTATATATAGCTATCTATATCTATATAGC pMM110 ON-switch TATTTTTTTTAACTTCCTTTATTTTCCTTCCAGGATTTTGCCACCATGCAAAATCAAAAAGA AGGAAGGTGCTCACATTCCTTAAATATAAGGAGTAAGTCTGCCAGCATTATGAAAGTGAA TCTTACTTTTGTAAAACTTTATGGTTTGTGGAAAACAAATGTTTTTGAACATTTAAAAAGTT CAGATGTTAGAAAGTTGAAAGGTTAATGTAAAACAATCAATATTAAAGAATTTTGATGCCA AAACTATTAGATAAAAGGTTAATCTACATCCCTACTAGAATTCTCATACTTAACTGGTTGG TTGTGTGGAAGAAACATACTTTCACAATAAAGAGCTTTAGGATATGATGCCATTTTATATC ACTAGTAGGCAGACCAGCAGACTTTTTTTTATTGTGATATGGGATAACCTAGGCATACTG CACTGTACACTCTGACATATGAAGTGCTCTAGTCAAGTTTAACTGGTGTCCACAGAGGAC ATGGTTTAACTGGAATTCGTCAAGCCTCTGGTTCTAATTTCTCATTTGCAGGAAATGCTG GCATAGAGCAGCAC ATAATTCCCCCACCACCTCCCATATGTCCAGATTCTCTTGATGATGCTGATGCTTTGGGA AGTGGCTTAATTTCATGGTACGGCAGTGGCTATCATACTGGCTATTATTTGGTAAGTAAT CACTCAGCATCTTTTCCTGACAATTTTTTTGTAGTTATGTGACTTTGTTTTGTAAATTTATA AAATACTACTTGCTTCTCTCTTTATATTACTAAAAAATAAAAATAAAAAAATACAACTGTCT GAGGCTTAAATTACTCTTGCATTGTCCCTAAGTATAATTTTAGTTAATTTTAAAAAGCTTTC ATGCTATCTTAACTGCAGCCTAATAATTGTTTTCTTTGGGATAACTTTTAAAGTACATTAAA AGACTATCAACTTAATTTCTGATCATATTTTGTTGAATAAAATAAGTAAAATGTCTTGTGAA ACAAAATGCTTTTTAACATCCATATAAAGCTATCTATATATAGCTATCTATATCTATATAGC pMM111 ON-switch TATTTTTTTTAACTTCCTTTATTTTCCTTCCAGGATTTTGCCACCATGCAAAATCAAAAAGA AGGAAGGTGCTCACATTCCTTAAATATAAGGAGTAAGTCTGCCAGCATTATGAAAGTGAA TCTTACTTTTGTAAAACTTTATGGTTTGTGGAAAACAAATGTTTTTGAACATTTAAAAAGTT CAGATGTTAGAAAGTTGAAAGGTTAATGTAAAACAATCAATATTAAAGAATTTTGATGCCA AAACTATTAGATAAAAGGTTAATCTACATCCCTACTAGAATTCTCATACTTAACTGGTTGG TTGTGTGGAAGAAACATACTTTCACAATAAAGAGCTTTAGGATATGATGCCATTTTATATC ACTAGTAGGCAGACCAGCAGACTTTTTTTTATTGTGATATGGGATAACCTAGGCATACTG CACTGTACACTCTGACATATGAAGTGCTCTAGTCAAGTTTAACTGGTGTCCACAGAGGAC ATGGTTTAACTGGAATTCGTCAAGCCTCTGGTTCTAATTTCTCATTTGCAGGAAATGCTG GCATAGAGCAGCAC ATAATTCCCCCACCACCTCCCATATGTCCAGATTCTCTTGATGATGCTGATGCTTTGGGA AGTGGCTTAATTTCATGGTACGGCAGTGGCTATCATACTGGCTATTATCTGGTAAGTAAT CACTCAGCATCTTTTCCTGACAATTTTTTTGTAGTTATGTGACTTTGTTTTGTAAATTTATA AAATACTACTTGCTTCTCTCTTTATATTACTAAAAAATAAAAATAAAAAAATACAACTGTCT GAGGCTTAAATTACTCTTGCATTGTCCCTAAGTATAATTTTAGTTAATTTTAAAAAGCTTTC ATGCTATCTTAACTGCAGCCTAATAATTGTTTTCTTTGGGATAACTTTTAAAGTACATTAAA AGACTATCAACTTAATTTCTGATCATATTTTGTTGAATAAAATAAGTAAAATGTCTTGTGAA pMM242 ON-switch ACAAAATGCTTTTTAACATCCATATAAAGCTATCTATATATAGCTATCTATATCTATATAGC TATTTTTTTTAACTTCCTTTATTTTCCTTCCAGGATTTTAGAGCCACCATGCAAAATCAAAA AGAAGGAAGGTGCTCACATTCCTTAAATATAAGGAGTAAGTCTGCCAGCATTATGAAAGT CCAAAACTATTAGATAAAAGGTTAATCTACATCCCTACTAGAATTCTCATACTTAACTGGT TGGTTGTGTGGAAGAAACATACTTTCACAATAAAGAGCTTTAGGATATGATGCCATTTTAT ATCACTAGTAGGCAGACCAGCAGACTTTTTTTTATTGTGATATGGGATAACCTAGGCATA P37829 CTGCACTGTACACTCTGACATATGAAGTGCTCTAGTCAAGTTTAACTGGTGTCCACAGAG GACATGGTTTAACTGGAATTCGTCAAGCCTCTGGTTCTAATTTCTCATTTGCAGGAAATG CTGGCATAGAGCAGCAC ATAATTCCCCCACCACCTCCCATATGTCCAGATTCTCTTGATGATGCTGATGCTTTGGGA AGTGGCTTAATTTCATGGTACGGCAGTGGCTATCATACTGGCTATTATCTGGTAAGTAAT CACTCAGCATCTTTTCCTGACAATTTTTTTGTAGTTATGTGACTTTGTTTTGTAAATTTATA AAATACTACTTGCTTCTCTCTTTATATTACTAAAAAATAAAAATAAAAAAATACAACTGTCT GAGGCTTAAATTACTCTTGCATTGTCCCTAAGTATAATTTTAGTTAATTTTAAAAAGCTTTC ATGCTATCTTAACTGCAGCCTAATAATTGTTTTCTTTGGGATAACTTTTAAAGTACATTAAA AGACTATCAACTTAATTTCTGATCATATTTTGTTGAATAAAATAAGTAAAATGTCTTGTGAA ACAAAATGCTTTTTAACATCCATATAAAGCTATCTATATATAGCTATCTATATCTATATAGC pMM243 ON-switch TATTTTTTTTAACTTCCTTTATTTTCCTTCCAGGATTTTAGACAAAATAGCACCATGCAAAA AGAAGGAAGGTGCTCACATTCCTTAAATATAAGGAGTAAGTCTGCCAGCATTATGAAAGT GAATCTTACTTTTGTAAAACTTTATGGTTTGTGGAAAACAAATGTTTTTGAACATTTAAAAA GTTCAGATGTTAGAAAGTTGAAAGGTTAATGTAAAACAATCAATATTAAAGAATTTTGATG CCAAAACTATTAGATAAAAGGTTAATCTACATCCCTACTAGAATTCTCATACTTAACTGGT TGGTTGTGTGGAAGAAACATACTTTCACAATAAAGAGCTTTAGGATATGATGCCATTTTAT ATCACTAGTAGGCAGACCAGCAGACTTTTTTTTATTGTGATATGGGATAACCTAGGCATA CTGCACTGTACACTCTGACATATGAAGTGCTCTAGTCAAGTTTAACTGGTGTCCACAGAG GACATGGTTTAACTGGAATTCGTCAAGCCTCTGGTTCTAATTTCTCATTTGCAGGAAATG CTGGCATAGAGCAGCAC ATAATTCCCCCACCACCTCCCATATGTCCAGATTCTCTTGATGATGCTGATGCTTTGGGA AGTGGCTTAATTTCATGGTACGGCAGTGGCTATCATACTGGCTATTATCTGGTAAGTAAT CACTCAGCATCTTTTCCTGACAATTTTTTTGTAGTTATGTGACTTTGTTTTGTAAATTTATA AAATACTACTTGCTTCTCTCTTTATATTACTAAAAAATAAAAATAAAAAAATACAACTGTCT GAGGCTTAAATTACTCTTGCATTGTCCCTAAGTATAATTTTAGTTAATTTTAAAAAGCTTTC ATGCTATCTTAACTGCAGCCTAATAATTGTTTTCTTTGGGATAACTTTTAAAGTACATTAAA AGACTATCAACTTAATTTCTGATCATATTTTGTTGAATAAAATAAGTAAAATGTCTTGTGAA ACAAAATGCTTTTTAACATCCATATAAAGCTATCTATATATAGCTATCTATATCTATATAGC pMM244 ON-switch TATTTTTTTTAACTTCCTTTATTTTCCTTCCAGGATTTTAGACAAAATAGCACCATGGAAAA AGAAGGAAGGTGCTCACATTCCTTAAATATAAGGAGTAAGTCTGCCAGCATTATGAAAGT GAATCTTACTTTTGTAAAACTTTATGGTTTGTGGAAAACAAATGTTTTTGAACATTTAAAAA GTTCAGATGTTAGAAAGTTGAAAGGTTAATGTAAAACAATCAATATTAAAGAATTTTGATG CCAAAACTATTAGATAAAAGGTTAATCTACATCCCTACTAGAATTCTCATACTTAACTGGT TGGTTGTGTGGAAGAAACATACTTTCACAATAAAGAGCTTTAGGATATGATGCCATTTTAT ATCACTAGTAGGCAGACCAGCAGACTTTTTTTTATTGTGATATGGGATAACCTAGGCATA CTGCACTGTACACTCTGACATATGAAGTGCTCTAGTCAAGTTTAACTGGTGTCCACAGAG GACATGGTTTAACTGGAATTCGTCAAGCCTCTGGTTCTAATTTCTCATTTGCAGGAAATG CTGGCATAGAGCAGCAC ATAATTCCCCCACCACCTCCCATATGTCCAGATTCTCTTGATGATGCTGATGCTTTGGGA AGTGGCTTAATTTCATGGTACGGCAGTGGCTATCATACTGGCTATTATCTGGTAAGTAAT CACTCAGCATCTTTTCCTGACAATTTTTTTGTAGTTATGTGACTTTGTTTTGTAAATTTATA AAATACTACTTGCTTCTCTCTTTATATTACTAAAAAATAAAAATAAAAAAATACAACTGTCT GAGGCTTAAATTACTCTTGCATTGTCCCTAAGTATAATTTTAGTTAATTTTAAAAAGCTTTC ATGCTATCTTAACTGCAGCCTAATAATTGTTTTCTTTGGGATAACTTTTAAAGTACATTAAA AGACTATCAACTTAATTTCTGATCATATTTTGTTGAATAAAATAAGTAAAATGTCTTGTGAA ACAAAATGCTTTTTAACATCCATATAAAGCTATCTATATATAGCTATCTATATCTATATAGC pMM245 ON-switch TATTTTTTTTAACTTCCTTTATTTTCCTTCCAGGATTTTAGACAAAATCACCATGGAAAAAG AAGGAAGGTGCTCACATTCCTTAAATATAAGGAGTAAGTCTGCCAGCATTATGAAAGTGA ATCTTACTTTTGTAAAACTTTATGGTTTGTGGAAAACAAATGTTTTTGAACATTTAAAAAGT TCAGATGTTAGAAAGTTGAAAGGTTAATGTAAAACAATCAATATTAAAGAATTTTGATGCC AAAACTATTAGATAAAAGGTTAATCTACATCCCTACTAGAATTCTCATACTTAACTGGTTG GTTGTGTGGAAGAAACATACTTTCACAATAAAGAGCTTTAGGATATGATGCCATTTTATAT CACTAGTAGGCAGACCAGCAGACTTTTTTTTATTGTGATATGGGATAACCTAGGCATACT GCACTGTACACTCTGACATATGAAGTGCTCTAGTCAAGTTTAACTGGTGTCCACAGAGGA CATGGTTTAACTGGAATTCGTCAAGCCTCTGGTTCTAATTTCTCATTTGCAGGAAATGCT GGCATAGAGCAGCAC ATAATTCCCCCACCACCTCCCATATGTCCAGATTCTCTTGATGATGCTGATGCTTTGGGA AGTGGCTTAATTTCATGGTACGGCAGTGGCTATCATACTGGCTATTATCTGGTAAGTAAT CACTCAGCATCTTTTCCTGACAATTTTTTTGTAGTTATGTGACTTTGTTTTGTAAATTTATA AAATACTACTTGCTTCTCTCTTTATATTACTAAAAAATAAAAATAAAAAAATACAACTGTCT GAGGCTTAAATTACTCTTGCATTGTCCCTAAGTATAATTTTAGTTAATTTTAAAAAGCTTTC ATGCTATCTTAACTGCAGCCTAATAATTGTTTTCTTTGGGATAACTTTTAAAGTACATTAAA pMM246 ON-switch AGACTATCAACTTAATTTCTGATCATATTTTGTTGAATAAAATAAGTAAAATGTCTTGTGAA ACAAAATGCTTTTTAACATCCATATAAAGCTATCTATATATAGCTATCTATATCTATATAGC TACTTTTGTAAAACTTTATGGTTTGTGGAAAACAAATGTTTTTGAACATTTAAAAAGTTCAG ATGTTAGAAAGTTGAAAGGTTAATGTAAAACAATCAATATTAAAGAATTTTGATGCCAAAA CTATTAGATAAAAGGTTAATCTACATCCCTACTAGAATTCTCATACTTAACTGGTTGGTTG TGTGGAAGAAACATACTTTCACAATAAAGAGCTTTAGGATATGATGCCATTTTATATCACT AGTAGGCAGACCAGCAGACTTTTTTTTATTGTGATATGGGATAACCTAGGCATACTGCAC TGTACACTCTGACATATGAAGTGCTCTAGTCAAGTTTAACTGGTGTCCACAGAGGACATG GTTTAACTGGAATTCGTCAAGCCTCTGGTTCTAATTTCTCATTTGCAGGAAATGCTGGCA TAGAGCAGCAC ATAATTCCCCCACCACCTCCCATATGTCCAGATTCTCTTGATGATGCTGATGCTTTGGGA AGTGGCTTAATTTCATGGTACGGCAGTGGCTATCATACTGGCTATTATCTGGTAAGTAAT CACTCAGCATCTTTTCCTGACAATTTTTTTGTAGTTATGTGACTTTGTTTTGTAAATTTATA AAATACTACTTGCTTCTCTCTTTATATTACTAAAAAATAAAAATAAAAAAATACAACTGTCT GAGGCTTAAATTACTCTTGCATTGTCCCTAAGTATAATTTTAGTTAATTTTAAAAAGCTTTC ATGCTATCTTAACTGCAGCCTAATAATTGTTTTCTTTGGGATAACTTTTAAAGTACATTAAA AGACTATCAACTTAATTTCTGATCATATTTTGTTGAATAAAATAAGTAAAATGTCTTGTGAA ACAAAATGCTTTTTAACATCCATATAAAGCTATCTATATATAGCTATCTATATCTATATAGC pMM247 ON-switch TATTTTTTTTAACTTCCTTTATTTTCCTTCCAGGATTTTAGACAAAATCAAAAAATGGAAGG AAGGTGCTCACATTCCTTAAATATAAGGAGTAAGTCTGCCAGCATTATGAAAGTGAATCT TACTTTTGTAAAACTTTATGGTTTGTGGAAAACAAATGTTTTTGAACATTTAAAAAGTTCAG ATGTTAGAAAGTTGAAAGGTTAATGTAAAACAATCAATATTAAAGAATTTTGATGCCAAAA CTATTAGATAAAAGGTTAATCTACATCCCTACTAGAATTCTCATACTTAACTGGTTGGTTG TGTGGAAGAAACATACTTTCACAATAAAGAGCTTTAGGATATGATGCCATTTTATATCACT AGTAGGCAGACCAGCAGACTTTTTTTTATTGTGATATGGGATAACCTAGGCATACTGCAC TGTACACTCTGACATATGAAGTGCTCTAGTCAAGTTTAACTGGTGTCCACAGAGGACATG GTTTAACTGGAATTCGTCAAGCCTCTGGTTCTAATTTCTCATTTGCAGGAAATGCTGGCA TAGAGCAGCAC ATAATTCCCCCACCACCTCCCATATGTCCAGATTCTCTTGATGATGCTGATGCTTTGGGA AGTGGCTTAATTTCATGGTACGGCAGTGGCTATCATACTGGCTATTATCAGGTAAGTAAT CACTCAGCATCTTTTCCTGACAATTTTTTTGTAGTTATGTGACTTTGTTTTGTAAATTTATA AAATACTACTTGCTTCTCTCTTTATATTACTAAAAAATAAAAATAAAAAAATACAACTGTCT GAGGCTTAAATTACTCTTGCATTGTCCCTAAGTATAATTTTAGTTAATTTTAAAAAGCTTTC ATGCTATCTTAACTGCAGCCTAATAATTGTTTTCTTTGGGATAACTTTTAAAGTACATTAAA AGACTATCAACTTAATTTCTGATCATATTTTGTTGAATAAAATAAGTAAAATGTCTTGTGAA ACAAAATGCTTTTTAACATCCATATAAAGCTATCTATATATAGCTATCTATATCTATATAGC pLS175 ON-switch TATTTTTTTTAACTTCCTTTATTTTCCTTCCAGGATTTTAGACAAAATCAAAAAGAAGGAAG GTGCTCACATTCCTTAAATATAAGGAGTAAGTCTGCCAGCATTATGAAAGTGAATCTTACT TTTGTAAAACTTTATGGTTTGTGGAAAACAAATGTTTTTGAACATTTAAAAAGTTCAGATGT TAGAAAGTTGAAAGGTTAATGTAAAACAATCAATATTAAAGAATTTTGATGCCAAAACTAT TAGATAAAAGGTTAATCTACATCCCTACTAGAATTCTCATACTTAACTGGTTGGTTGTGTG GAAGAAACATACTTTCACAATAAAGAGCTTTAGGATATGATGCCATTTTATATCACTAGTA GGCAGACCAGCAGACTTTTTTTTATTGTGATATGGGATAACCTAGGCATACTGCACTGTA CACTCTGACATATGAAGTGCTCTAGTCAAGTTTAACTGGTGTCCACAGAGGACATGGTTT AACTGGAATTCGTCAAGCCTCTGGTTCTAATTTCTCATTTGCAGGAAATGCTGGCATAGA GCAGCAC ATAATTCCCCCACCACCTCCCATATGTCCAGATTCTCTTGATGATGCTGATGCTTTGGGA AGTGGCTTAATTTCATGGTACGGCAGTGGCTATCATACTGGCTATTATCAGGTAAGTAAT CACTCAGCATCTTTTCCTGACAATTTTTTTGTAGTTATGTGACTTTGTTTTGTAAATTTATA AAATACTACTTGCTTCTCTCTTTATATTACTAAAAAATAAAAATAAAAAAATACAACTGTCT GAGGCTTAAATTACTCTTGCATTGTCCCTAAGTATAATTTTAGTTAATTTTAAAAAGCTTTC ATGCTATCTTAACTGCAGCCTAATAATTGTTTTCTTTGGGATAACTTTTAAAGTACATTAAA AGACTATCAACTTAATTTCTGATCATATTTTGTTGAATAAAATAAGTAAAATGTCTTGTGAA ACAAAATGCTTTTTAACATCCATATAAAGCTATCTATATATAGCTATCTATATCTATATAGC pMM123 ON-switch TATTTTTTTTAACTTCCTTTATTTTCCTTCCAGGATTTTAGACAAAATCAAAAAGAAGGAAG GTGCTCACATTCCTTAAATATAATGGAGTAAGTCTGCCAGCATTATGAAAGTGAATCTTAC TTTTGTAAAACTTTATGGTTTGTGGAAAACAAATGTTTTTGAACATTTAAAAAGTTCAGATG TTAGAAAGTTGAAAGGTTAATGTAAAACAATCAATATTAAAGAATTTTGATGCCAAAACTA TTAGATAAAAGGTTAATCTACATCCCTACTAGAATTCTCATACTTAACTGGTTGGTTGTGT GGAAGAAACATACTTTCACAATAAAGAGCTTTAGGATATGATGCCATTTTATATCACTAGT AGGCAGACCAGCAGACTTTTTTTTATTGTGATATGGGATAACCTAGGCATACTGCACTGT ACACTCTGACATATGAAGTGCTCTAGTCAAGTTTAACTGGTGTCCACAGAGGACATGGTT TAACTGGAATTCGTCAAGCCTCTGGTTCTAATTTCTCATTTGCAGGAAATGCTGGCATAG AGCAGCAC ATAATTCCCCCACCACCTCCCATATGTCCAGATTCTCTTGATGATGCTGATGCTTTGGGA AGTGGCTTAATTTCATGGTACGGCAGTGGCTATCATACTGGCTATTATCAGGTAAGTAAT CACTCAGCATCTTTTCCTGACAATTTTTTTGTAGTTATGTGACTTTGTTTTGTAAATTTATA AAATACTACTTGCTTCTCTCTTTATATTACTAAAAAATAAAAATAAAAAAATACAACTGTCT GAGGCTTAAATTACTCTTGCATTGTCCCTAAGTATAATTTTAGTTAATTTTAAAAAGCTTTC pMM124 ON-switch ATGCTATCTTAACTGCAGCCTAATAATTGTTTTCTTTGGGATAACTTTTAAAGTACATTAAA TATTTTTTTTAACTTCCTTTATTTTCCTTCCAGGATTTTAGACAAAATCAAAAAGAAGGAAG GTGCTCACATTCCTTAAATGGTAAGGAGTAAGTCTGCCAGCATTATGAAAGTGAATCTTA CTTTTGTAAAACTTTATGGTTTGTGGAAAACAAATGTTTTTGAACATTTAAAAAGTTCAGAT GTTAGAAAGTTGAAAGGTTAATGTAAAACAATCAATATTAAAGAATTTTGATGCCAAAACT ATTAGATAAAAGGTTAATCTACATCCCTACTAGAATTCTCATACTTAACTGGTTGGTTGTG TGGAAGAAACATACTTTCACAATAAAGAGCTTTAGGATATGATGCCATTTTATATCACTAG TAGGCAGACCAGCAGACTTTTTTTTATTGTGATATGGGATAACCTAGGCATACTGCACTG TACACTCTGACATATGAAGTGCTCTAGTCAAGTTTAACTGGTGTCCACAGAGGACATGGT TTAACTGGAATTCGTCAAGCCTCTGGTTCTAATTTCTCATTTGCAGGAAATGCTGGCATA GAGCAGCAC ATAATTCCCCCACCACCTCCCATATGTCCAGATTCTCTTGATGATGCTGATGCTTTGGGA AGTGGCTTAATTTCATGGTACGGCAGTGGCTATCATACTGGCTATTATCAGGTAAGTAAT CACTCAGCATCTTTTCCTGACAATTTTTTTGTAGTTATGTGACTTTGTTTTGTAAATTTATA AAATACTACTTGCTTCTCTCTTTATATTACTAAAAAATAAAAATAAAAAAATACAACTGTCT GAGGCTTAAATTACTCTTGCATTGTCCCTAAGTATAATTTTAGTTAATTTTAAAAAGCTTTC ATGCTATCTTAACTGCAGCCTAATAATTGTTTTCTTTGGGATAACTTTTAAAGTACATTAAA AGACTATCAACTTAATTTCTGATCATATTTTGTTGAATAAAATAAGTAAAATGTCTTGTGAA ACAAAATGCTTTTTAACATCCATATAAAGCTATCTATATATAGCTATCTATATCTATATAGC pMM125 ON-switch TATTTTTTTTAACTTCCTTTATTTTCCTTCCAGGATTTTAGACAAAATCAAAAAGAAGGAAG GATGGCGTCACATTCCTTAAATATAAGGAGTAAGTCTGCCAGCATTATGAAAGTGAATCT TACTTTTGTAAAACTTTATGGTTTGTGGAAAACAAATGTTTTTGAACATTTAAAAAGTTCAG ATGTTAGAAAGTTGAAAGGTTAATGTAAAACAATCAATATTAAAGAATTTTGATGCCAAAA CTATTAGATAAAAGGTTAATCTACATCCCTACTAGAATTCTCATACTTAACTGGTTGGTTG TGTGGAAGAAACATACTTTCACAATAAAGAGCTTTAGGATATGATGCCATTTTATATCACT AGTAGGCAGACCAGCAGACTTTTTTTTATTGTGATATGGGATAACCTAGGCATACTGCAC TGTACACTCTGACATATGAAGTGCTCTAGTCAAGTTTAACTGGTGTCCACAGAGGACATG GTTTAACTGGAATTCGTCAAGCCTCTGGTTCTAATTTCTCATTTGCAGGAAATGCTGGCA TAGAGCAGCAC ATAATTCCCCCACCACCTCCCATATGTCCAGATTCTCTTGATGATGCTGATGCTTTGGGA AGTGGCTTAATTTCATGGTACGGCAGTGGCTATCATACTGGCTATTATCAGGTAAGTAAT CACTCAGCATCTTTTCCTGACAATTTTTTTGTAGTTATGTGACTTTGTTTTGTAAATTTATA AAATACTACTTGCTTCTCTCTTTATATTACTAAAAAATAAAAATAAAAAAATACAACTGTCT GAGGCTTAAATTACTCTTGCATTGTCCCTAAGTATAATTTTAGTTAATTTTAAAAAGCTTTC ATGCTATCTTAACTGCAGCCTAATAATTGTTTTCTTTGGGATAACTTTTAAAGTACATTAAA AGACTATCAACTTAATTTCTGATCATATTTTGTTGAATAAAATAAGTAAAATGTCTTGTGAA ACAAAATGCTTTTTAACATCCATATAAAGCTATCTATATATAGCTATCTATATCTATATAGC pMM126 ON-switch TATTTTTTTTAACTTCCTTTATTTTCCTTCCAGGATTTTAGACAAAATCAAAAAGAAGGAAG GTGCTCACATGTCCTTAAATATAAGGAGTAAGTCTGCCAGCATTATGAAAGTGAATCTTA CTTTTGTAAAACTTTATGGTTTGTGGAAAACAAATGTTTTTGAACATTTAAAAAGTTCAGAT GTTAGAAAGTTGAAAGGTTAATGTAAAACAATCAATATTAAAGAATTTTGATGCCAAAACT ATTAGATAAAAGGTTAATCTACATCCCTACTAGAATTCTCATACTTAACTGGTTGGTTGTG TGGAAGAAACATACTTTCACAATAAAGAGCTTTAGGATATGATGCCATTTTATATCACTAG TAGGCAGACCAGCAGACTTTTTTTTATTGTGATATGGGATAACCTAGGCATACTGCACTG TACACTCTGACATATGAAGTGCTCTAGTCAAGTTTAACTGGTGTCCACAGAGGACATGGT TTAACTGGAATTCGTCAAGCCTCTGGTTCTAATTTCTCATTTGCAGGAAATGCTGGCATA GAGCAGCAC ATAATTCCCCCACCACCTCCCATATGTCCAGATTCTCTTGATGATGCTGATGCTTTGGGA AGTGGCTTAATTTCATGGTACGGCAGTGGCTATCATACTGGCTATTATCAGGTAAGTAAT CACTCAGCATCTTTTCCTGACAATTTTTTTGTAGTTATGTGACTTTGTTTTGTAAATTTATA AAATACTACTTGCTTCTCTCTTTATATTACTAAAAAATAAAAATAAAAAAATACAACTGTCT GAGGCTTAAATTACTCTTGCATTGTCCCTAAGTATAATTTTAGTTAATTTTAAAAAGCTTTC ATGCTATCTTAACTGCAGCCTAATAATTGTTTTCTTTGGGATAACTTTTAAAGTACATTAAA AGACTATCAACTTAATTTCTGATCATATTTTGTTGAATAAAATAAGTAAAATGTCTTGTGAA ACAAAATGCTTTTTAACATCCATATAAAGCTATCTATATATAGCTATCTATATCTATATAGC pMM127 ON-switch TATTTTTTTTAACTTCCTTTATTTTCCTTCCAGGATTTTAGACAAAATCAAAAAGAAGGAAG GTGCTCACATTCCTATGGATATAAGGAGTAAGTCTGCCAGCATTATGAAAGTGAATCTTA CTTTTGTAAAACTTTATGGTTTGTGGAAAACAAATGTTTTTGAACATTTAAAAAGTTCAGAT GTTAGAAAGTTGAAAGGTTAATGTAAAACAATCAATATTAAAGAATTTTGATGCCAAAACT ATTAGATAAAAGGTTAATCTACATCCCTACTAGAATTCTCATACTTAACTGGTTGGTTGTG TGGAAGAAACATACTTTCACAATAAAGAGCTTTAGGATATGATGCCATTTTATATCACTAG TAGGCAGACCAGCAGACTTTTTTTTATTGTGATATGGGATAACCTAGGCATACTGCACTG TACACTCTGACATATGAAGTGCTCTAGTCAAGTTTAACTGGTGTCCACAGAGGACATGGT TTAACTGGAATTCGTCAAGCCTCTGGTTCTAATTTCTCATTTGCAGGAAATGCTGGCATA GAGCAGCAC ATAATTCCCCCACCACCTCCCATATGTCCAGATTCTCTTGATGATGCTGATGCTTTGGGA AGTGGCTTAATTTCATGGTACGGCAGTGGCTATCATACTGGCTATTATCAGGTAAGTAAT CACTCAGCATCTTTTCCTGACAATTTTTTTGTAGTTATGTGACTTTGTTTTGTAAATTTATA AAATACTACTTGCTTCTCTCTTTATATTACTAAAAAATAAAAATAAAAAAATACAACTGTCT pMM128 ON-switch AGACTATCAACTTAATTTCTGATCATATTTTGTTGAATAAAATAAGTAAAATGTCTTGTGAA ACAAAATGCTTTTTAACATCCATATAAAGCTATCTATATATAGCTATCTATATCTATATAGC TATTTTTTTTAACTTCCTTTATTTTCCTTCCAGGATTTTAGACAAAATCAAAAAGAAGGAAG P37829 GTGCTCACATTCCTTAAATATAAGATGAGTAAGTCTGCCAGCATTATGAAAGTGAATCTTA CTTTTGTAAAACTTTATGGTTTGTGGAAAACAAATGTTTTTGAACATTTAAAAAGTTCAGAT GTTAGAAAGTTGAAAGGTTAATGTAAAACAATCAATATTAAAGAATTTTGATGCCAAAACT ATTAGATAAAAGGTTAATCTACATCCCTACTAGAATTCTCATACTTAACTGGTTGGTTGTG TGGAAGAAACATACTTTCACAATAAAGAGCTTTAGGATATGATGCCATTTTATATCACTAG TAGGCAGACCAGCAGACTTTTTTTTATTGTGATATGGGATAACCTAGGCATACTGCACTG TACACTCTGACATATGAAGTGCTCTAGTCAAGTTTAACTGGTGTCCACAGAGGACATGGT TTAACTGGAATTCGTCAAGCCTCTGGTTCTAATTTCTCATTTGCAGGAAATGCTGGCATA GAGCAGCAC ATAATTCCCCCACCACCTCCCATATGTCCAGATTCTCTTGATGATGCTGATGCTTTGGGA AGTGGCTTAATTTCATGGTACGGCAGTGGCTATCATACTGGCTATTATCAGGTAAGTAAT CACTCAGCATCTTTTCCTGACAATTTTTTTGTAGTTATGTGACTTTGTTTTGTAAATTTATA AAATACTACTTGCTTCTCTCTTTATATTACTAAAAAATAAAAATAAAAAAATACAACTGTCT GAGGCTTAAATTACTCTTGCATTGTCCCTAAGTATAATTTTAGTTAATTTTAAAAAGCTTTC ATGCTATCTTAACTGCAGCCTAATAATTGTTTTCTTTGGGATAACTTTTAAAGTACATTAAA AGACTATCAACTTAATTTCTGATCATATTTTGTTGAATAAAATAAGTAAAATGTCTTGTGAA ACAAAATGCTTTTTAACATCCATATAAAGCTATCTATATATAGCTATCTATATCTATATAGC pMM129 ON-switch TATTTTTTTTAACTTCCTTTATTTTCCTTCCAGGATTTTAGACAAAATCAAAAAGAAGGAAG GTGCTCACATTCCTTAAATGAGGAGTAAGTCTGCCAGCATTATGAAAGTGAATCTTACTT TTGTAAAACTTTATGGTTTGTGGAAAACAAATGTTTTTGAACATTTAAAAAGTTCAGATGTT AGAAAGTTGAAAGGTTAATGTAAAACAATCAATATTAAAGAATTTTGATGCCAAAACTATT AGATAAAAGGTTAATCTACATCCCTACTAGAATTCTCATACTTAACTGGTTGGTTGTGTGG AAGAAACATACTTTCACAATAAAGAGCTTTAGGATATGATGCCATTTTATATCACTAGTAG GCAGACCAGCAGACTTTTTTTTATTGTGATATGGGATAACCTAGGCATACTGCACTGTAC ACTCTGACATATGAAGTGCTCTAGTCAAGTTTAACTGGTGTCCACAGAGGACATGGTTTA ACTGGAATTCGTCAAGCCTCTGGTTCTAATTTCTCATTTGCAGGAAATGCTGGCATAGAG CAGCAC ATAATTCCCCCACCACCTCCCATATGTCCAGATTCTCTTGATGATGCTGATGCTTTGGGA AGTGGCTTAATTTCATGGTACGGCAGTGGCTATCATACTGGCTATTATCAGGTAAGTAAT CACTCAGCATCTTTTCCTGACAATTTTTTTGTAGTTATGTGACTTTGTTTTGTAAATTTATA AAATACTACTTGCTTCTCTCTTTATATTACTAAAAAATAAAAATAAAAAAATACAACTGTCT GAGGCTTAAATTACTCTTGCATTGTCCCTAAGTATAATTTTAGTTAATTTTAAAAAGCTTTC ATGCTATCTTAACTGCAGCCTAATAATTGTTTTCTTTGGGATAACTTTTAAAGTACATTAAA AGACTATCAACTTAATTTCTGATCATATTTTGTTGAATAAAATAAGTAAAATGTCTTGTGAA ACAAAATGCTTTTTAACATCCATATAAAGCTATCTATATATAGCTATCTATATCTATATAGC pMM201 ON-switch TATTTTTTTTAACTTCCTTTATTTTCCTTCCAGGATTTTAGACAAAATCAAAAAGAAGGAAG GTGCTCACATGGCCTTAAATATAAGGAGTAAGTCTGCCAGCATTATGAAAGTGAATCTTA CTTTTGTAAAACTTTATGGTTTGTGGAAAACAAATGTTTTTGAACATTTAAAAAGTTCAGAT GTTAGAAAGTTGAAAGGTTAATGTAAAACAATCAATATTAAAGAATTTTGATGCCAAAACT ATTAGATAAAAGGTTAATCTACATCCCTACTAGAATTCTCATACTTAACTGGTTGGTTGTG TGGAAGAAACATACTTTCACAATAAAGAGCTTTAGGATATGATGCCATTTTATATCACTAG TAGGCAGACCAGCAGACTTTTTTTTATTGTGATATGGGATAACCTAGGCATACTGCACTG TACACTCTGACATATGAAGTGCTCTAGTCAAGTTTAACTGGTGTCCACAGAGGACATGGT TTAACTGGAATTCGTCAAGCCTCTGGTTCTAATTTCTCATTTGCAGGAAATGCTGGCATA GAGCAGCAC ATAATTCCCCCACCACCTCCCATATGTCCAGATTCTCTTGATGATGCTGATGCTTTGGGA AGTGGCTTAATTTCATGGTACGGCAGTGGCTATCATACTGGCTATTATCAGGTAAGTAAT CACTCAGCATCTTTTCCTGACAATTTTTTTGTAGTTATGTGACTTTGTTTTGTAAATTTATA AAATACTACTTGCTTCTCTCTTTATATTACTAAAAAATAAAAATAAAAAAATACAACTGTCT GAGGCTTAAATTACTCTTGCATTGTCCCTAAGTATAATTTTAGTTAATTTTAAAAAGCTTTC ATGCTATCTTAACTGCAGCCTAATAATTGTTTTCTTTGGGATAACTTTTAAAGTACATTAAA AGACTATCAACTTAATTTCTGATCATATTTTGTTGAATAAAATAAGTAAAATGTCTTGTGAA ACAAAATGCTTTTTAACATCCATATAAAGCTATCTATATATAGCTATCTATATCTATATAGC pMM202 ON-switch TATTTTTTTTAACTTCCTTTATTTTCCTTCCAGGATTTTAGACAAAATCAAAAAGAAGGAAG GTGCTAACATGGCCTTAAATATAAGGAGTAAGTCTGCCAGCATTATGAAAGTGAATCTTA CTTTTGTAAAACTTTATGGTTTGTGGAAAACAAATGTTTTTGAACATTTAAAAAGTTCAGAT GTTAGAAAGTTGAAAGGTTAATGTAAAACAATCAATATTAAAGAATTTTGATGCCAAAACT ATTAGATAAAAGGTTAATCTACATCCCTACTAGAATTCTCATACTTAACTGGTTGGTTGTG TGGAAGAAACATACTTTCACAATAAAGAGCTTTAGGATATGATGCCATTTTATATCACTAG TAGGCAGACCAGCAGACTTTTTTTTATTGTGATATGGGATAACCTAGGCATACTGCACTG TACACTCTGACATATGAAGTGCTCTAGTCAAGTTTAACTGGTGTCCACAGAGGACATGGT TTAACTGGAATTCGTCAAGCCTCTGGTTCTAATTTCTCATTTGCAGGAAATGCTGGCATA GAGCAGCAC ATAATTCCCCCACCACCTCCCATATGTCCAGATTCTCTTGATGATGCTGATGCTTTGGGA AGTGGCTTAATTTCATGGTACGGCAGTGGCTATCATACTGGCTATTATCAGGTAAGTAAT pMM203 ON-switch GAGGCTTAAATTACTCTTGCATTGTCCCTAAGTATAATTTTAGTTAATTTTAAAAAGCTTTC ATGCTATCTTAACTGCAGCCTAATAATTGTTTTCTTTGGGATAACTTTTAAAGTACATTAAA AGACTATCAACTTAATTTCTGATCATATTTTGTTGAATAAAATAAGTAAAATGTCTTGTGAA P37829 ACAAAATGCTTTTTAACATCCATATAAAGCTATCTATATATAGCTATCTATATCTATATAGC TATTTTTTTTAACTTCCTTTATTTTCCTTCCAGGATTTTAGACAAAATCAAAAAGAAGGAAG GTGCTCACATATGCCTAAATTAAGGAGTAAGTCTGCCAGCATTATGAAAGTGAATCTTAC TTTTGTAAAACTTTATGGTTTGTGGAAAACAAATGTTTTTGAACATTTAAAAAGTTCAGATG TTAGAAAGTTGAAAGGTTAATGTAAAACAATCAATATTAAAGAATTTTGATGCCAAAACTA TTAGATAAAAGGTTAATCTACATCCCTACTAGAATTCTCATACTTAACTGGTTGGTTGTGT GGAAGAAACATACTTTCACAATAAAGAGCTTTAGGATATGATGCCATTTTATATCACTAGT AGGCAGACCAGCAGACTTTTTTTTATTGTGATATGGGATAACCTAGGCATACTGCACTGT ACACTCTGACATATGAAGTGCTCTAGTCAAGTTTAACTGGTGTCCACAGAGGACATGGTT TAACTGGAATTCGTCAAGCCTCTGGTTCTAATTTCTCATTTGCAGGAAATGCTGGCATAG AGCAGCAC ATAATTCCCCCACCACCTCCCATATGTCCAGATTCTCTTGATGATGCTGATGCTTTGGGA AGTGGCTTAATTTCATGGTACGGCAGTGGCTATCATACTGGCTATTATCAGGTAAGTAAT CACTCAGCATCTTTTCCTGACAATTTTTTTGTAGTTATGTGACTTTGTTTTGTAAATTTATA AAATACTACTTGCTTCTCTCTTTATATTACTAAAAAATAAAAATAAAAAAATACAACTGTCT GAGGCTTAAATTACTCTTGCATTGTCCCTAAGTATAATTTTAGTTAATTTTAAAAAGCTTTC ATGCTATCTTAACTGCAGCCTAATAATTGTTTTCTTTGGGATAACTTTTAAAGTACATTAAA AGACTATCAACTTAATTTCTGATCATATTTTGTTGAATAAAATAAGTAAAATGTCTTGTGAA ACAAAATGCTTTTTAACATCCATATAAAGCTATCTATATATAGCTATCTATATCTATATAGC pMM204 ON-switch TATTTTTTTTAACTTCCTTTATTTTCCTTCCAGGATTTTAGACAAAATCAAAAAGAAGGAAG GTGCTCACATTCCATGTTAAATATAAGGAGTAAGTCTGCCAGCATTATGAAAGTGAATCT TACTTTTGTAAAACTTTATGGTTTGTGGAAAACAAATGTTTTTGAACATTTAAAAAGTTCAG ATGTTAGAAAGTTGAAAGGTTAATGTAAAACAATCAATATTAAAGAATTTTGATGCCAAAA CTATTAGATAAAAGGTTAATCTACATCCCTACTAGAATTCTCATACTTAACTGGTTGGTTG TGTGGAAGAAACATACTTTCACAATAAAGAGCTTTAGGATATGATGCCATTTTATATCACT AGTAGGCAGACCAGCAGACTTTTTTTTATTGTGATATGGGATAACCTAGGCATACTGCAC TGTACACTCTGACATATGAAGTGCTCTAGTCAAGTTTAACTGGTGTCCACAGAGGACATG GTTTAACTGGAATTCGTCAAGCCTCTGGTTCTAATTTCTCATTTGCAGGAAATGCTGGCA TAGAGCAGCAC ATAATTCCCCCACCACCTCCCATATGTCCAGATTCTCTTGATGATGCTGATGCTTTGGGA AGTGGCTTAATTTCATGGTACGGCAGTGGCTATCATACTGGCTATTATCAGGTAAGTAAT CACTCAGCATCTTTTCCTGACAATTTTTTTGTAGTTATGTGACTTTGTTTTGTAAATTTATA AAATACTACTTGCTTCTCTCTTTATATTACTAAAAAATAAAAATAAAAAAATACAACTGTCT GAGGCTTAAATTACTCTTGCATTGTCCCTAAGTATAATTTTAGTTAATTTTAAAAAGCTTTC ATGCTATCTTAACTGCAGCCTAATAATTGTTTTCTTTGGGATAACTTTTAAAGTACATTAAA AGACTATCAACTTAATTTCTGATCATATTTTGTTGAATAAAATAAGTAAAATGTCTTGTGAA ACAAAATGCTTTTTAACATCCATATAAAGCTATCTATATATAGCTATCTATATCTATATAGC pMM205 ON-switch TATTTTTTTTAACTTCCTTTATTTTCCTTCCAGGATTTTAGACAAAATCAAAAAGAAGGAAG GTGCTCACATTCCTTATGAATATAAGGAGTAAGTCTGCCAGCATTATGAAAGTGAATCTT ACTTTTGTAAAACTTTATGGTTTGTGGAAAACAAATGTTTTTGAACATTTAAAAAGTTCAGA TGTTAGAAAGTTGAAAGGTTAATGTAAAACAATCAATATTAAAGAATTTTGATGCCAAAAC TATTAGATAAAAGGTTAATCTACATCCCTACTAGAATTCTCATACTTAACTGGTTGGTTGT GTGGAAGAAACATACTTTCACAATAAAGAGCTTTAGGATATGATGCCATTTTATATCACTA GTAGGCAGACCAGCAGACTTTTTTTTATTGTGATATGGGATAACCTAGGCATACTGCACT GTACACTCTGACATATGAAGTGCTCTAGTCAAGTTTAACTGGTGTCCACAGAGGACATGG TTTAACTGGAATTCGTCAAGCCTCTGGTTCTAATTTCTCATTTGCAGGAAATGCTGGCATA GAGCAGCAC ATAATTCCCCCACCACCTCCCATATGTCCAGATTCTCTTGATGATGCTGATGCTTTGGGA AGTGGCTTAATTTCATGGTACGGCAGTGGCTATCATACTGGCTATTATCAGGTAAGTAAT CACTCAGCATCTTTTCCTGACAATTTTTTTGTAGTTATGTGACTTTGTTTTGTAAATTTATA AAATACTACTTGCTTCTCTCTTTATATTACTAAAAAATAAAAATAAAAAAATACAACTGTCT GAGGCTTAAATTACTCTTGCATTGTCCCTAAGTATAATTTTAGTTAATTTTAAAAAGCTTTC ATGCTATCTTAACTGCAGCCTAATAATTGTTTTCTTTGGGATAACTTTTAAAGTACATTAAA AGACTATCAACTTAATTTCTGATCATATTTTGTTGAATAAAATAAGTAAAATGTCTTGTGAA ACAAAATGCTTTTTAACATCCATATAAAGCTATCTATATATAGCTATCTATATCTATATAGC pMM206 ON-switch TATTTTTTTTAACTTCCTTTATTTTCCTTCCAGGATTTTAGACAAAATCAAAAAGAAGGAAG GTGCTCACATTCCTTATGGAAAATATAAGGAGTAAGTCTGCCAGCATTATGAAAGTGAAT CTTACTTTTGTAAAACTTTATGGTTTGTGGAAAACAAATGTTTTTGAACATTTAAAAAGTTC AGATGTTAGAAAGTTGAAAGGTTAATGTAAAACAATCAATATTAAAGAATTTTGATGCCAA AACTATTAGATAAAAGGTTAATCTACATCCCTACTAGAATTCTCATACTTAACTGGTTGGT TGTGTGGAAGAAACATACTTTCACAATAAAGAGCTTTAGGATATGATGCCATTTTATATCA CTAGTAGGCAGACCAGCAGACTTTTTTTTATTGTGATATGGGATAACCTAGGCATACTGC ACTGTACACTCTGACATATGAAGTGCTCTAGTCAAGTTTAACTGGTGTCCACAGAGGACA TGGTTTAACTGGAATTCGTCAAGCCTCTGGTTCTAATTTCTCATTTGCAGGAAATGCTGG CATAGAGCAGCAC pMM248 ON-switch CACTCAGCATCTTTTCCTGACAATTTTTTTGTAGTTATGTGACTTTGTTTTGTAAATTTATA AAATACTACTTGCTTCTCTCTTTATATTACTAAAAAATAAAAATAAAAAAATACAACTGTCT GAGGCTTAAATTACTCTTGCATTGTCCCTAAGTATAATTTTAGTTAATTTTAAAAAGCTTTC P37829 ATGCTATCTTAACTGCAGCCTAATAATTGTTTTCTTTGGGATAACTTTTAAAGTACATTAAA AGACTATCAACTTAATTTCTGATCATATTTTGTTGAATAAAATAAGTAAAATGTCTTGTGAA ACAAAATGCTTTTTAACATCCATATAAAGCTATCTATATATAGCTATCTATATCTATATAGC TATTTTTTTTAACTTCCTTTATTTTCCTTCCAGGATTTTAGACAAAATCAAAAAGAAGGAAG GTGCTCACATTCCTTAAATTAAGATGAGTAAGTCTGCCAGCATTATGAAAGTGAATCTTAC TTTTGTAAAACTTTATGGTTTGTGGAAAACAAATGTTTTTGAACATTTAAAAAGTTCAGATG TTAGAAAGTTGAAAGGTTAATGTAAAACAATCAATATTAAAGAATTTTGATGCCAAAACTA TTAGATAAAAGGTTAATCTACATCCCTACTAGAATTCTCATACTTAACTGGTTGGTTGTGT GGAAGAAACATACTTTCACAATAAAGAGCTTTAGGATATGATGCCATTTTATATCACTAGT AGGCAGACCAGCAGACTTTTTTTTATTGTGATATGGGATAACCTAGGCATACTGCACTGT ACACTCTGACATATGAAGTGCTCTAGTCAAGTTTAACTGGTGTCCACAGAGGACATGGTT TAACTGGAATTCGTCAAGCCTCTGGTTCTAATTTCTCATTTGCAGGAAATGCTGGCATAG AGCAGCAC ATAATTCCCCCACCACCTCCCATATGTCCAGATTCTCTTGATGATGCTGATGCTTTGGGA AGTGGCTTAATTTCATGGTACGGCAGTGGCTATCATACTGGCTATTATCAGGTAAGTAAT CACTCAGCATCTTTTCCTGACAATTTTTTTGTAGTTATGTGACTTTGTTTTGTAAATTTATA AAATACTACTTGCTTCTCTCTTTATATTACTAAAAAATAAAAATAAAAAAATACAACTGTCT GAGGCTTAAATTACTCTTGCATTGTCCCTAAGTATAATTTTAGTTAATTTTAAAAAGCTTTC ATGCTATCTTAACTGCAGCCTAATAATTGTTTTCTTTGGGATAACTTTTAAAGTACATTAAA AGACTATCAACTTAATTTCTGATCATATTTTGTTGAATAAAATAAGTAAAATGTCTTGTGAA ACAAAATGCTTTTTAACATCCATATAAAGCTATCTATATATAGCTATCTATATCTATATAGC pMM249 ON-switch TATTTTTTTTAACTTCCTTTATTTTCCTTCCAGGATTTTAGACAAAATCAAAAAGAAGGAAG GTGCTCACATTCCTAAAATGAGGAGTAAGTCTGCCAGCATTATGAAAGTGAATCTTACTT TTGTAAAACTTTATGGTTTGTGGAAAACAAATGTTTTTGAACATTTAAAAAGTTCAGATGTT AGAAAGTTGAAAGGTTAATGTAAAACAATCAATATTAAAGAATTTTGATGCCAAAACTATT AGATAAAAGGTTAATCTACATCCCTACTAGAATTCTCATACTTAACTGGTTGGTTGTGTGG AAGAAACATACTTTCACAATAAAGAGCTTTAGGATATGATGCCATTTTATATCACTAGTAG GCAGACCAGCAGACTTTTTTTTATTGTGATATGGGATAACCTAGGCATACTGCACTGTAC ACTCTGACATATGAAGTGCTCTAGTCAAGTTTAACTGGTGTCCACAGAGGACATGGTTTA ACTGGAATTCGTCAAGCCTCTGGTTCTAATTTCTCATTTGCAGGAAATGCTGGCATAGAG CAGCAC ATAATTCCCCCACCACCTCCCATATGTCCAGATTCTCTTGATGATGCTGATGCTTTGGGA AGTGGCTTAATTTCATGGTACGGCAGTGGCTATCATACTGGCTATTATCAGGTAAGTAAT CACTCAGCATCTTTTCCTGACAATTTTTTTGTAGTTATGTGACTTTGTTTTGTAAATTTATA AAATACTACTTGCTTCTCTCTTTATATTACTAAAAAATAAAAATAAAAAAATACAACTGTCT GAGGCTTAAATTACTCTTGCATTGTCCCTAAGTATAATTTTAGTTAATTTTAAAAAGCTTTC ATGCTATCTTAACTGCAGCCTAATAATTGTTTTCTTTGGGATAACTTTTAAAGTACATTAAA AGACTATCAACTTAATTTCTGATCATATTTTGTTGAATAAAATAAGTAAAATGTCTTGTGAA ACAAAATGCTTTTTAACATCCATATAAAGCTATCTATATATAGCTATCTATATCTATATAGC pMM250 ON-switch TATTTTTTTTAACTTCCTTTATTTTCCTTCCAGGATTTTAGACAAAATCAAAAAGAAGGAAG GTGCTCACATTCCTGAAATGAGGAGTAAGTCTGCCAGCATTATGAAAGTGAATCTTACTT TTGTAAAACTTTATGGTTTGTGGAAAACAAATGTTTTTGAACATTTAAAAAGTTCAGATGTT AGAAAGTTGAAAGGTTAATGTAAAACAATCAATATTAAAGAATTTTGATGCCAAAACTATT AGATAAAAGGTTAATCTACATCCCTACTAGAATTCTCATACTTAACTGGTTGGTTGTGTGG AAGAAACATACTTTCACAATAAAGAGCTTTAGGATATGATGCCATTTTATATCACTAGTAG GCAGACCAGCAGACTTTTTTTTATTGTGATATGGGATAACCTAGGCATACTGCACTGTAC ACTCTGACATATGAAGTGCTCTAGTCAAGTTTAACTGGTGTCCACAGAGGACATGGTTTA ACTGGAATTCGTCAAGCCTCTGGTTCTAATTTCTCATTTGCAGGAAATGCTGGCATAGAG CAGCAC ATAATTCCCCCACCACCTCCCATATGTCCAGATTCTCTTGATGATGCTGATGCTTTGGGA AGTGGCTTAATTTCATGGTACGGCAGTGGCTATCATACTGGCTATTATCAGGTAAGTAAT CACTCAGCATCTTTTCCTGACAATTTTTTTGTAGTTATGTGACTTTGTTTTGTAAATTTATA AAATACTACTTGCTTCTCTCTTTATATTACTAAAAAATAAAAATAAAAAAATACAACTGTCT GAGGCTTAAATTACTCTTGCATTGTCCCTAAGTATAATTTTAGTTAATTTTAAAAAGCTTTC ATGCTATCTTAACTGCAGCCTAATAATTGTTTTCTTTGGGATAACTTTTAAAGTACATTAAA AGACTATCAACTTAATTTCTGATCATATTTTGTTGAATAAAATAAGTAAAATGTCTTGTGAA ACAAAATGCTTTTTAACATCCATATAAAGCTATCTATATATAGCTATCTATATCTATATAGC pMM251 ON-switch TATTTTTTTTAACTTCCTTTATTTTCCTTCCAGGATTTTAGACAAAATCAAAAAGAAGGAAG GTGCTCACATTCAAAATGAGGAGTAAGTCTGCCAGCATTATGAAAGTGAATCTTACTTTT GTAAAACTTTATGGTTTGTGGAAAACAAATGTTTTTGAACATTTAAAAAGTTCAGATGTTA GAAAGTTGAAAGGTTAATGTAAAACAATCAATATTAAAGAATTTTGATGCCAAAACTATTA GATAAAAGGTTAATCTACATCCCTACTAGAATTCTCATACTTAACTGGTTGGTTGTGTGGA AGAAACATACTTTCACAATAAAGAGCTTTAGGATATGATGCCATTTTATATCACTAGTAGG CAGACCAGCAGACTTTTTTTTATTGTGATATGGGATAACCTAGGCATACTGCACTGTACA CTCTGACATATGAAGTGCTCTAGTCAAGTTTAACTGGTGTCCACAGAGGACATGGTTTAA AGCAC GCAATTTCATGGTACGGCAGTGGCTATCATACTGGCTATTATCAGGTAAGTAATCACTCA pMM252 ON-switch GCATCTTTTCCTGACAATTTTTTTGTAGTTATGTGACTTTGTTTTGTAAATTTATAAAATAC TACTTGCTTCTCTCTTTATATTACTTTAAAAGACTATCAACTTAATTTCTGATCATATTTTGT P37829 TGAATAAAATAAGTAAAATGTCTTGTGAAACAAAATGCTTTTTAACATCCATATAAAGCTAT CTATATATAGCTATCTATATCTATATAGCTATTTTTTTTAACTTCCTTTATTTTCCTTCCAGG ATTTTAGACAAAATCAAAAAGAAGGAAGGTGCTCACATTCCTTAAATATAAGGAGTAAGT CTGCCAGCATTATGAAAGTGAATCTTACTTTTGTAAAACTTTATGGTTTGTGGAAAACAAA TGTTTTTGAACATTTAAAAAGTTCAGATGTTAGAACTTTTTTTTATTGTGATATGGGATAAC CTAGGCATACTGCACTGTACACTCTGACATATGAAGTGCTCTAGTCAAGTTTAACTGGTG TCCACAGAGGACATGGTTTAACTGGAATTCGTCAAGCCTCTGGTTCTAATTTCTCATTTG CAGGA GCAATTTCATGGTACGGCAGTGGCTATCATACTGGCTATTATCAGGTAAGTAATCACTCA GCATCTTTTCCTGACAATTTTTTTGTAGTTATGTGACTTTGTTTTGTAAATTTATAAAATAC TACTTGCTTCTCTCTTTATATTACTTTAAAAGACTATCAACTTAATTTCTGATCATATTTTGT TGAATAAAATAAGTAAAATGTCTTGTGAAACAAAATGCTTTTTAACATCCATATAAAGCTAT CTATATATAGCTATCTATATCTATATAGCTATTTTTTTTAACTTCCTTTATTTTCCTTCCAGG pMM254 ON-switch ATTTTAGACAAAATCAAAAAGAAGGAAGGTGCTCACATGTCCTTAAATATAAGGAGTAAG TCTGCCAGCATTATGAAAGTGAATCTTACTTTTGTAAAACTTTATGGTTTGTGGAAAACAA ATGTTTTTGAACATTTAAAAAGTTCAGATGTTAGAACTTTTTTTTATTGTGATATGGGATAA CCTAGGCATACTGCACTGTACACTCTGACATATGAAGTGCTCTAGTCAAGTTTAACTGGT GTCCACAGAGGACATGGTTTAACTGGAATTCGTCAAGCCTCTGGTTCTAATTTCTCATTT GCAGGA GCAATTTCATGGTACGGCAGTGGCTATCATACTGGCTATTATCAGGTAAGTAATCACTCA GCATCTTTTCCTGACAATTTTTTTGTAGTTATGTGACTTTGTTTTGTAAATTTATAAAATAC TACTTGCTTCTCTCTTTATATTACTTTAAAAGACTATCAACTTAATTTCTGATCATATTTTGT TGAATAAAATAAGTAAAATGTCTTGTGAAACAAAATGCTTTTTAACATCCATATAAAGCTAT CTATATATAGCTATCTATATCTATATAGCTATTTTTTTTAACTTCCTTTATTTTCCTTCCAGG pMM255 ON-switch ATTTTAGACAAAATCAAAAAGAAGGAAGGTGCTCACATTCCTTAAATATAAGATGAGTAAG TCTGCCAGCATTATGAAAGTGAATCTTACTTTTGTAAAACTTTATGGTTTGTGGAAAACAA ATGTTTTTGAACATTTAAAAAGTTCAGATGTTAGAACTTTTTTTTATTGTGATATGGGATAA CCTAGGCATACTGCACTGTACACTCTGACATATGAAGTGCTCTAGTCAAGTTTAACTGGT GTCCACAGAGGACATGGTTTAACTGGAATTCGTCAAGCCTCTGGTTCTAATTTCTCATTT GCAGGA GCAATTTCATGGTACGGCAGTGGCTATCATACTGGCTATTATCAGGTAAGTAATCACTCA GCATCTTTTCCTGACAATTTTTTTGTAGTTATGTGACTTTGTTTTGTAAATTTATAAAATAC TACTTGCTTCTCTCTTTATATTACTTTAAAAGACTATCAACTTAATTTCTGATCATATTTTGT TGAATAAAATAAGTAAAATGTCTTGTGAAACAAAATGCTTTTTAACATCCATATAAAGCTAT CTATATATAGCTATCTATATCTATATAGCTATTTTTTTTAACTTCCTTTATTTTCCTTCCAGG pMM256 ON-switch ATTTTAGACAAAATCAAAAAGAAGGAAGGTGCTCACATTCCTTAAATGAGGAGTAAGTCT GCCAGCATTATGAAAGTGAATCTTACTTTTGTAAAACTTTATGGTTTGTGGAAAACAAATG TTTTTGAACATTTAAAAAGTTCAGATGTTAGAACTTTTTTTTATTGTGATATGGGATAACCT AGGCATACTGCACTGTACACTCTGACATATGAAGTGCTCTAGTCAAGTTTAACTGGTGTC CACAGAGGACATGGTTTAACTGGAATTCGTCAAGCCTCTGGTTCTAATTTCTCATTTGCA GGA GCAATTTCATGGTACGGCAGTGGCTATCATACTGGCTATTATCAGGTAAGTAATCACTCA GCATCTTTTCCTGACAATTTTTTTGTAGTTATGTGACTTTGTTTTGTAAATTTATAAAATAC TACTTGCTTCTCTCTTTATATTACTTTAAAAGACTATCAACTTAATTTCTGATCATATTTTGT TGAATAAAATAAGTAAAATGTCTTGTGAAACAAAATGCTTTTTAACATCCATATAAAGCTAT CTATATATAGCTATCTATATCTATATAGCTATTTTTTTTAACTTCCTTTATTTTCCTTCCAGG pMM257 ON-switch ATTTTAGACAAAATCAAAAAGAAGGAAGGTGCTCACATTCCTTAAATGATAAGGAGTAAG TCTGCCAGCATTATGAAAGTGAATCTTACTTTTGTAAAACTTTATGGTTTGTGGAAAACAA ATGTTTTTGAACATTTAAAAAGTTCAGATGTTAGAACTTTTTTTTATTGTGATATGGGATAA CCTAGGCATACTGCACTGTACACTCTGACATATGAAGTGCTCTAGTCAAGTTTAACTGGT GTCCACAGAGGACATGGTTTAACTGGAATTCGTCAAGCCTCTGGTTCTAATTTCTCATTT GCAGGA ATAATTCCCCCACCACCTCCCATATGTCCAGATTCTCTTGATGATGCTGATGCTTTGGGA AGTGGCTTAATTTCATGGTACGGCAGTGGCTATCATACTGGCTATTATCAGGTAAGTAAT CACTCAGCATCTTTTCCTGACAATTTTTTTGTAGTTATGTGACTTTGTTTTGTAAATTTATA AAATACTACTTGCTTCTCTCTTTATATTACTAAAAAATAAAAATAAAAAAATACAACTGTCT GAGGCTTAAATTACTCTTGCATTGTCCCTAAGTATAATTTTAGTTAATTTTAAAAAGCTTTC ATGCTATCTTAACTGCAGCCTAATAATTGTTTTCTTTGGGATAACTTTTAAAGTACATTAAA AGACTATCAACTTAATTTCTGATCATATTTTGTTGAATAAAATAAGTAAAATGTCTTGTGAA ACAAAATGCTTTTTAACATCCATATAAAGCTATCTATATATAGCTATCTATATCTATATAGC pMM199 ON-switch TATTTTTTTTAACTTCCTTTATTTTCCTTCCAGGATTTTAGACAAAATCAAAAAGAAGGAAG GTGCTCACATTCCTTAAATATAAGGAGTAAGTCTGCCAGCATTATGAAAGTGAATCTTACT TTTGTAAAACTTTATGGTTTGTGGAAAACAAATGTTTTTGAACATTTAAAAAGTTCAGATGT TAGAAAGTTGAAAGGTTAATGTAAAACAATCAATATTAAAGAATTTTGATGCCAAAACTAT TAGATAAAAGGTTAATCTACATCCCTACTAGAATTCTCATACTTAACTGGTTGGTTGTGTG GAAGAAACATACTTTCACAATAAAGAGCTTTAGGATATGATGCCATTTTATATCACTAGTA GGCAGACCAGCAGACTTTTTTTTATTGTGATATGGGATAACCTAGGCATACTGCACTGTA CACTCTGACATATGAAGTGCTCTAGTCAAGTTTAACTGGTGTCCACAGAGGACATGGTTT AACTGGAATTCGTCAAGCCTCTGGTTCTAATTTCTCATTTCCAGTGAATGCTGGCATAGA GCAGCAC P37829 ATAATTCCCCCACCACCTCCCATATGTCCAGATTCTCTTGATGATGCTGATGCTTTGGGA AGTGGCTTAATTTCATGGTACGGCAGTGGCTATCATACTGGCTATTATCAGGTAAGTAAT CACTCAGCATCTTTTCCTGACAATTTTTTTGTAGTTATGTGACTTTGTTTTGTAAATTTATA AAATACTACTTGCTTCTCTCTTTATATTACTAAAAAATAAAAATAAAAAAATACAACTGTCT GAGGCTTAAATTACTCTTGCATTGTCCCTAAGTATAATTTTAGTTAATTTTAAAAAGCTTTC ATGCTATCTTAACTGCAGCCTAATAATTGTTTTCTTTGGGATAACTTTTAAAGTACATTAAA AGACTATCAACTTAATTTCTGATCATATTTTGTTGAATAAAATAAGTAAAATGTCTTGTGAA ACAAAATGCTTTTTAACATCCATATAAAGCTATCTATATATAGCTATCTATATCTATATAGC pMM200 ON-switch TATTTTTTTTAACTTCCTTTATTTTCCTTCCAGGATTTTAGACAAAATCAAAAAGAAGGAAG GTGCTCACATTCCTTAAATATAAGGAGTAAGTCTGCCAGCATTATGAAAGTGAATCTTACT TTTGTAAAACTTTATGGTTTGTGGAAAACAAATGTTTTTGAACATTTAAAAAGTTCAGATGT TAGAAAGTTGAAAGGTTAATGTAAAACAATCAATATTAAAGAATTTTGATGCCAAAACTAT TAGATAAAAGGTTAATCTACATCCCTACTAGAATTCTCATACTTAACTGGTTGGTTGTGTG GAAGAAACATACTTTCACAATAAAGAGCTTTAGGATATGATGCCATTTTATATCACTAGTA GGCAGACCAGCAGACTTTTTTTTATTGTGATATGGGATAACCTAGGCATACTGCACTGTA CACTCTGACATATGAAGTGCTCTAGTCAAGTTTAACTGGTGTCCACAGAGGACATGGTTT AACTGGAATTCGTCAAGCCTCTGGTTCTAATTTCTTTTTTTCAGTGAATGCTGGCATAGAG CAGCAC ATAATTCCCCCACCACCTCCCATATGTCCAGATTCTCTTGATGATGCTGATGCTTTGGGA AGTGGCTTAATTTCATGGTACGGCAGTGGCTATCATACTGGCTATTATCAGGTAAGTAAT CACTCAGCATCTTTTCCTGACAATTTTTTTGTAGTTATGTGACTTTGTTTTGTAAATTTATA AAATACTACTTGCTTCTCTCTTTATATTACTAAAAAATAAAAATAAAAAAATACAACTGTCT GAGGCTTAAATTACTCTTGCATTGTCCCTAAGTATAATTTTAGTTAATTTTAAAAAGCTTTC ATGCTATCTTAACTGCAGCCTAATAATTGTTTTCTTTGGGATAACTTTTAAAGTACATTAAA AGACTATCAACTTAATTTCTGATCATATTTTGTTGAATAAAATAAGTAAAATGTCTTGTGAA ACAAAATGCTTTTTAACATCCATATAAAGCTATCTATATATAGCTATCTATATCTATATAGC pMM236 ON-switch TATTTTTTTTAACTTCCTTTATTTTCCTTCCAGGATTTTAGACAAAATCAAAAAGAAGGAAG GTGCTCACATTCCTTAAATATAAGGAGTAAGTCTGCCAGCATTATGAAAGTGAATCTTACT TTTGTAAAACTTTATGGTTTGTGGAAAACAAATGTTTTTGAACATTTAAAAAGTTCAGATGT TAGAAAGTTGAAAGGTTAATGTAAAACAATCAATATTAAAGAATTTTGATGCCAAAACTAT TAGATAAAAGGTTAATCTACATCCCTACTAGAATTCTCATACTTAACTGGTTGGTTGTGTG GAAGAAACATACTTTCACAATAAAGAGCTTTAGGATATGATGCCATTTTATATCACTAGTA GGCAGACCAGCAGACTTTTTTTTATTGTGATATGGGATAACCTAGGCATACTGCACTGTA CACTCTGACATATGAAGTGCTCTAGTCAAGTTTAACTGGTGTCCACAGAGGACATGGTTT AACTGGAATTCGTCAAGCCTCTGGTTCTAATTTCTCATTTGCAGATGAATGCTGGCATAG AGCAGCAC ATAATTCCCCCACCACCTCCCATATGTCCAGATTCTCTTGATGATGCTGATGCTTTGGGA AGTGGCTTAATTTCATGGTACGGCAGTGGCTATCATACTGGCTATTATTAGGTAAGTAAT CACTCAGCATCTTTTCCTGACAATTTTTTTGTAGTTATGTGACTTTGTTTTGTAAATTTATA AAATACTACTTGCTTCTCTCTTTATATTACTAAAAAATAAAAATAAAAAAATACAACTGTCT GAGGCTTAAATTACTCTTGCATTGTCCCTAAGTATAATTTTAGTTAATTTTAAAAAGCTTTC ATGCTATCTTAACTGCAGCCTAATAATTGTTTTCTTTGGGATAACTTTTAAAGTACATTAAA AGACTATCAACTTAATTTCTGATCATATTTTGTTGAATAAAATAAGTAAAATGTCTTGTGAA ACAAAATGCTTTTTAACATCCATATAAAGCTATCTATATATAGCTATCTATATCTATATAGC pMM237 ON-switch TATTTTTTTTAACTTCCTTTATTTTCCTTCCAGGATTTTAGACAAAATCAAAAAGAAGGAAG GTGCTCACATTCCTTAAATATAAGGAGTAAGTCTGCCAGCATTATGAAAGTGAATCTTACT TTTGTAAAACTTTATGGTTTGTGGAAAACAAATGTTTTTGAACATTTAAAAAGTTCAGATGT TAGAAAGTTGAAAGGTTAATGTAAAACAATCAATATTAAAGAATTTTGATGCCAAAACTAT TAGATAAAAGGTTAATCTACATCCCTACTAGAATTCTCATACTTAACTGGTTGGTTGTGTG GAAGAAACATACTTTCACAATAAAGAGCTTTAGGATATGATGCCATTTTATATCACTAGTA GGCAGACCAGCAGACTTTTTTTTATTGTGATATGGGATAACCTAGGCATACTGCACTGTA CACTCTGACATATGAAGTGCTCTAGTCAAGTTTAACTGGTGTCCACAGAGGACATGGTTT AACTGGAATTCGTCAAGCCTCTGGTTCTAATTTCTCATTTGCAGATGAATGCTGGCATAG AGCAGCAC ATAATTCCCCCACCACCTCCCATATGTCCAGATTCTCTTGATGATGCTGATGCTTTGGGA AGTGGCTTAATTTCATGGTACGGCAGTGGCTATCATACTGGCTATTATTTGGTAAGTAAT CACTCAGCATCTTTTCCTGACAATTTTTTTGTAGTTATGTGACTTTGTTTTGTAAATTTATA AAATACTACTTGCTTCTCTCTTTATATTACTAAAAAATAAAAATAAAAAAATACAACTGTCT GAGGCTTAAATTACTCTTGCATTGTCCCTAAGTATAATTTTAGTTAATTTTAAAAAGCTTTC ATGCTATCTTAACTGCAGCCTAATAATTGTTTTCTTTGGGATAACTTTTAAAGTACATTAAA AGACTATCAACTTAATTTCTGATCATATTTTGTTGAATAAAATAAGTAAAATGTCTTGTGAA pMM238 ON-switch ACAAAATGCTTTTTAACATCCATATAAAGCTATCTATATATAGCTATCTATATCTATATAGC TATTTTTTTTAACTTCCTTTATTTTCCTTCCAGGATTTTAGACAAAATCAAAAAGAAGGAAG GTGCTCACATTCCTTAAATATAAGGAGTAAGTCTGCCAGCATTATGAAAGTGAATCTTACT TTTGTAAAACTTTATGGTTTGTGGAAAACAAATGTTTTTGAACATTTAAAAAGTTCAGATGT TAGAAAGTTGAAAGGTTAATGTAAAACAATCAATATTAAAGAATTTTGATGCCAAAACTAT TAGATAAAAGGTTAATCTACATCCCTACTAGAATTCTCATACTTAACTGGTTGGTTGTGTG GAAGAAACA...

Claims

P37829 Claims:

1. A polynucleotide comprising in 5’ to 3’ order: (i) a first nucleotide sequence, comprising a nucleotide sequence having at least 80% sequence identity to a nucleotide sequence according to SEQ ID NO:222, wherein the first nucleotide sequence does not comprise SEQ ID NO:2; (ii) a second nucleotide sequence, comprising a nucleotide sequence having at least 80% sequence identity to SEQ ID NO:7 at its 5’ end, and comprising a nucleotide sequence having at least 80% sequence identity to a nucleotide sequence according to SEQ ID NO:378 at its 3’ end, and consisting of fewer than 1044 nucleotides; (iii) a third nucleotide sequence consisting of a nucleotide sequence having at least 80% sequence identity to a nucleotide sequence according to SEQ ID NO:226; (iv) a fourth nucleotide sequence, comprising a nucleotide sequence having at least 80% sequence identity to a nucleotide sequence according to SEQ ID NO:380 at its 5’ end, and comprising a nucleotide sequence having at least 80% sequence identity to SEQ ID NO:16 at its 3’ end; (v) a fifth nucleotide sequence: (a) consisting of the dinucleotide ‘GA’, ‘TG’ or ‘TT’, or (b) comprising a nucleotide sequence having at least 80% sequence identity to a nucleotide sequence according to SEQ ID NO:19, wherein the nucleotide sequence comprises ‘GA’, ‘TG’ or ‘TT’ at the positions corresponding to positions 1 and 2 of SEQ ID NO:19, or (c) encoding a polypeptide of interest, and comprising ‘GA’, ‘TG’ or ‘TT’ at positions 1 and 2; and (vi) where the fifth nucleotide sequence is a nucleotide sequence according to (v)(a) or (v)(b), a sixth nucleotide sequence encoding a polypeptide of interest; wherein the polynucleotide comprises a start codon 5’ to the nucleotide sequence encoding a polypeptide of interest.

2. The polynucleotide according to claim 1, wherein when the polynucleotide is a polyribonucleotide, splicing of the polyribonucleotide in the absence of a splicing modifier that promotes SMN2 exon 7 inclusion yields polyribonucleotides substantially lacking the third nucleotide sequence.

3. The polynucleotide according to claim 1 or claim 2, wherein the first nucleotide sequence comprises a nucleotide sequence according to SEQ ID NO:

222.

4. The polynucleotide according to any one of claims 1 to 3, wherein the first nucleotide sequence comprises, or consists of, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:106, SEQ ID NO:219 or SEQ ID NO:

220.

5. The polynucleotide according to any one of claims 1 to 4, wherein the second nucleotide sequence comprises SEQ ID NO:7 at its 5’ end, and comprises SEQ ID NO:8 or SEQ ID NO:377 at its 3’ end.

6. The polynucleotide according to any one of claims 1 to 5, wherein the second nucleotide sequence consists of fewer than 500 nucleotides.P37829 7. The polynucleotide according to any one of claims 1 to 6, wherein the second nucleotide sequence comprises, or consists of, SEQ ID NO:9, SEQ ID NO:10 or SEQ ID NO:

228.

8. The polynucleotide according to any one of claims 1 to 7, wherein the third nucleotide sequence consists of a nucleotide sequence according to SEQ ID NO:

226.

9. The polynucleotide according to any one of claims 1 to 8, wherein the third nucleotide sequence consists of SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:223 or SEQ ID NO:

224.

10. The polynucleotide according to any one of claims 1 to 9, wherein the fourth nucleotide sequence comprises SEQ ID NO:15 or SEQ ID NO:379 at its 5’ end, and comprises SEQ ID NO:16 at its 3’ end.

11. The polynucleotide according to any one of claims 1 to 10, wherein the fourth nucleotide sequence consists of fewer than 500 nucleotides.

12. The polynucleotide according to any one of claims 1 to 11, wherein the fourth nucleotide sequence comprises, or consists of, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:227 or SEQ ID NO:

340.

13. The polynucleotide according to any one of claims 1 to 12, wherein the fifth nucleotide sequence: (a) consists of the dinucleotide ‘GA’ or ‘TG’, or (b) comprises, or consists of, a nucleotide sequence according to SEQ ID NO:

19.

14. The polynucleotide according to any one of claims 1 to 13, wherein the fifth nucleotide sequence: (a) consists of the dinucleotide ‘GA’ or ‘TG’, or (b) comprises, or consists of, SEQ ID NO:20 or SEQ ID NO:

21.

15. The polynucleotide according to any one of claims 1 to 14, wherein the polynucleotide comprises a nucleotide sequence having at least 80% sequence identity to a nucleotide sequence selected from the group consisting of SEQ ID NO:164, SEQ ID NO:171, SEQ ID NO:116, SEQ ID NO:114, SEQ ID NO:111, SEQ ID NO:25, SEQ ID NO:23, SEQ ID NO:24 and SEQ ID NO:

22.

16. The polynucleotide according to any one of claims 1 to 15, wherein the polynucleotide further comprises a promoter sequence 5’ to the start codon.

17. The polynucleotide according to any one of claims 1 to 16, wherein the polynucleotide further comprises a polyadenylation sequence 3’ to the nucleotide sequence encoding a polypeptide of interest.

18. The polynucleotide according to any one of claims 1 to 17, wherein the polynucleotide comprises an inverted terminal repeat (ITR) sequence at its 5’ end, and an ITR sequence at its 3’ end.

19. A vector comprising a polynucleotide according to any one of claims 1 to 18.P37829 20. The vector according to claim 19, wherein the vector is an adeno-associated virus (AAV) vector.

21. A pharmaceutical composition comprising a polynucleotide according to any one of claims 1 to 18, or a vector according to claim 19 or claim 20, and a pharmaceutically-acceptable carrier, diluent, excipient or adjuvant.

22. A cell comprising a polynucleotide according to any one of claims 1 to 18, or a vector according to claim 19 or claim 20.

23. The cell according to claim 22, wherein the cell further comprises a splicing modifier that promotes SMN2 exon 7 inclusion, optionally wherein the splicing modifier that promotes SMN2 exon 7 inclusion is risdiplam.

24. A method for modifying a cell to express a polypeptide of interest, comprising: (i) introducing into a cell a polynucleotide according to any one of claims 1 to 18, or a vector according to claim 19 or claim 20; and (ii) subsequently contacting the cell with a splicing modifier that promotes SMN2 exon 7 inclusion, optionally wherein the splicing modifier that promotes SMN2 exon 7 inclusion is risdiplam.

25. A method for expressing a polypeptide of interest in a cell, comprising contacting a cell according to claim 22 with a splicing modifier that promotes SMN2 exon 7 inclusion, optionally wherein the splicing modifier that promotes SMN2 exon 7 inclusion is risdiplam.

26. A polynucleotide according to any one of claims 1 to 18, a vector according to claim 19 or claim 20, or a pharmaceutical composition according to claim 21, for use in a method of medical treatment or prophylaxis.

27. A polynucleotide according to any one of claims 1 to 18, a vector according to claim 19 or claim 20, or a pharmaceutical composition according to claim 21, for use in treating or preventing a disease or condition that would derive therapeutic or prophylactic benefit from an increase in the level of expression of the polypeptide of interest.

28. Use of a polynucleotide according to any one of claims 1 to 18, a vector according to claim 19 or claim 20, or a pharmaceutical composition according to claim 21, in the manufacture of a medicament for treating or preventing a disease or condition that would derive therapeutic or prophylactic benefit from an increase in the level of expression of the polypeptide of interest.

29. A method of treating or preventing a disease or condition that would derive therapeutic or prophylactic benefit from an increase in the level of expression of the polypeptide of interest, comprising administering to a subject a polynucleotide according to any one of claims 1 to 18, a vector according to claim 19 or claim 20, or a pharmaceutical composition according to claim 21.P37829 30. The polynucleotide, vector, or pharmaceutical composition for use according to claim 27, the use according to claim 28, or the method according to claim 29, wherein treating or preventing the disease or condition further comprises administering to the subject a splicing modifier that promotes SMN2 exon 7 inclusion, optionally wherein the splicing modifier that promotes SMN2 exon 7 inclusion is risdiplam.

31. The polynucleotide, vector, or pharmaceutical composition for use according to claim 27 or claim 30, the use according to claim 28 or claim 30, or the method according to claim 29 or claim 30, wherein the disease or condition is a disease or condition characterised by deficiency of the polypeptide of interest.

32. A kit, comprising: (i) a polynucleotide according to any one of claims 1 to 18, a vector according to claim 19 or claim 20, or a pharmaceutical composition according to claim 21; and (ii) a splicing modifier that promotes SMN2 exon 7 inclusion, optionally wherein the splicing modifier that promotes SMN2 exon 7 inclusion is risdiplam.

33. A polynucleotide comprising in 5’ to 3’ order: (i) a first nucleotide sequence, comprising a nucleotide sequence having at least 80% sequence identity to a nucleotide sequence according to SEQ ID NO:1, wherein the first nucleotide sequence does not comprise SEQ ID NO:2; (ii) a second nucleotide sequence, comprising a nucleotide sequence having at least 80% sequence identity to SEQ ID NO:7 at its 5’ end, and comprising a nucleotide sequence having at least 80% sequence identity to SEQ ID NO:8 at its 3’ end, and consisting of fewer than 1044 nucleotides; (iii) a third nucleotide sequence consisting of a nucleotide sequence having at least 80% sequence identity to a nucleotide sequence according to SEQ ID NO:26, wherein the third nucleotide sequence comprises ‘A’ at the position corresponding to position 2 of SEQ ID NO:12; (iv) a fourth nucleotide sequence, comprising a nucleotide sequence having at least 80% sequence identity to SEQ ID NO:15 at its 5’ end, and comprising a nucleotide sequence having at least 80% sequence identity to SEQ ID NO:16 at its 3’ end; (v) a fifth nucleotide sequence: (a) consisting of the trinucleotide ‘GAG’ or (b) encoding a polypeptide of interest, and comprising ‘GAG’ at positions 1 to 3; and (vi) where the fifth nucleotide sequence is a nucleotide sequence according to (v)(a), a sixth nucleotide sequence encoding a polypeptide of interest; wherein the polynucleotide comprises a start codon 5’ to the nucleotide sequence encoding a polypeptide of interest.

34. The polynucleotide according to claim 33, wherein when the polynucleotide is a polyribonucleotide, splicing of the polyribonucleotide in the absence of a splicing modifier that promotes SMN2 exon 7 inclusion yields polyribonucleotides substantially lacking the third nucleotide sequence.

35. The polynucleotide according to claim 33 or claim 34, wherein the first nucleotide sequence comprises a nucleotide sequence according to SEQ ID NO:1.P37829 36. The polynucleotide according to any one of claims 33 to 35, wherein the first nucleotide sequence comprises, or consists of, SEQ ID NO:

3.

37. The polynucleotide according to any one of claims 33 to 36, wherein the second nucleotide sequence comprises SEQ ID NO:7 at its 5’ end, and comprises SEQ ID NO:8 at its 3’ end.

38. The polynucleotide according to any one of claims 33 to 37, wherein the second nucleotide sequence consists of fewer than 500 nucleotides.

39. The polynucleotide according to any one of claims 33 to 38, wherein the second nucleotide sequence comprises, or consists of, SEQ ID NO:

10.

40. The polynucleotide according to any one of claims 33 to 39, wherein the third nucleotide sequence consists of a nucleotide sequence according to SEQ ID NO:

26.

41. The polynucleotide according to any one of claims 33 to 40, wherein the third nucleotide sequence consists of SEQ ID NO:13 or SEQ ID NO:

27.

42. The polynucleotide according to any one of claims 33 to 41, wherein the fourth nucleotide sequence comprises SEQ ID NO:15 at its 5’ end, and comprises SEQ ID NO:16 at its 3’ end.

43. The polynucleotide according to any one of claims 33 to 42, wherein the fourth nucleotide sequence consists of fewer than 500 nucleotides.

44. The polynucleotide according to any one of claims 33 to 43, wherein the fourth nucleotide sequence comprises, or consists of, SEQ ID NO:

17.

45. The polynucleotide according to any one of claims 33 to 44, wherein the polynucleotide comprises at least 80% sequence identity to SEQ ID NO:28 or SEQ ID NO:

29.

46. The polynucleotide according to any one of claims 33 to 45, wherein the polynucleotide further comprises a promoter sequence 5’ to the start codon.

47. The polynucleotide according to any one of claims 33 to 46, wherein the polynucleotide further comprises a polyadenylation sequence 3’ to the nucleotide sequence encoding a polypeptide of interest.

48. The polynucleotide according to any one of claims 33 to 47, wherein the polynucleotide comprises an inverted terminal repeat (ITR) sequence at its 5’ end, and an ITR sequence at its 3’ end.

49. A vector comprising a polynucleotide according to any one of claims 33 to 48.

50. The vector according to claim 49, wherein the vector is an adeno-associated virus (AAV) vector.P37829 51. A pharmaceutical composition comprising a polynucleotide according to any one of claims 33 to 48, or a vector according to claim 49 or claim 50, and a pharmaceutically-acceptable carrier, diluent, excipient or adjuvant.

52. A cell comprising a polynucleotide according to any one of claims 33 to 48, or a vector according to claim 49 or claim 50.

53. The cell according to claim 52, wherein the cell further comprises a splicing modifier that promotes SMN2 exon 7 inclusion, optionally wherein the splicing modifier that promotes SMN2 exon 7 inclusion is risdiplam.

54. A method for modifying a cell to express a polypeptide of interest, comprising introducing into a cell a polynucleotide according to any one of claims 33 to 48, or a vector according to claim 49 or claim 50.

55. A method for inhibiting expression of a polypeptide of interest in a cell, comprising contacting a cell according to claim 52 with a splicing modifier that promotes SMN2 exon 7 inclusion, optionally wherein the splicing modifier that promotes SMN2 exon 7 inclusion is risdiplam.

56. A polynucleotide according to any one of claims 33 to 48, a vector according to claim 49 or claim 50, or a pharmaceutical composition according to claim 51, for use in a method of medical treatment or prophylaxis.

57. A polynucleotide according to any one of claims 33 to 48, a vector according to claim 49 or claim 50, or a pharmaceutical composition according to claim 51, for use in treating or preventing a disease or condition that would derive therapeutic or prophylactic benefit from an increase in the level of expression of the polypeptide of interest.

58. Use of a polynucleotide according to any one of claims 33 to 48, a vector according to claim 49 or claim 50, or a pharmaceutical composition according to claim 51, in the manufacture of a medicament for treating or preventing a disease or condition that would derive therapeutic or prophylactic benefit from an increase in the level of expression of the polypeptide of interest.

59. A method of treating or preventing a disease or condition that would derive therapeutic or prophylactic benefit from an increase in the level of expression of the polypeptide of interest, comprising administering to a subject a polynucleotide according to any one of claims 33 to 48, a vector according to claim 49 or claim 50, or a pharmaceutical composition according to claim 51.

60. The polynucleotide, vector, or pharmaceutical composition for use according to claim 57, the use according to claim 58, or the method according to claim 59, wherein the disease or condition is a disease or condition characterised by deficiency of the polypeptide of interest.P37829 61. A kit, comprising: (i) a polynucleotide according to any one of claims 33 to 48, a vector according to claim 49 or claim 50, or a pharmaceutical composition according to claim 51; and (ii) a splicing modifier that promotes SMN2 exon 7 inclusion, optionally wherein the splicing modifier that promotes SMN2 exon 7 inclusion is risdiplam.

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