Polynucleotides, AAV vectors, and pharmaceutical compositions for treating nephrotic syndrome

Abstract

The present invention relates to a polynucleotide comprising: a 5' ITR; a kidney-specific promoter; a regulatory element comprising a spliceosomal intron or a fragment thereof comprising a branch point sequence, a polypyrimidine tract, and a 3' splice acceptor site; a protein-coding sequence encoding podocin; and a 3' ITR.

Description

[0001]POLYNUCLEOTIDES, AAV VECTORS, AND PHARMACEUTICAL COMPOSITIONS FOR TREATING NEPHROTIC SYNDROME FIELD OF THE INVENTION The present invention relates to polynucleotides, AAV vectors, and pharmaceutical compositions for treating nephrotic syndrome. BACKGROUND TO THE INVENTION Nephrotic syndrome is a chronic kidney disease characterized by significant proteinuria, hypoalbuminemia, oedema and hyperlipidemia, and is the most common primary glomerular disease in children, affecting 2 / 100,000 children below the age of 16 in Europe and the USA. Nephrotic syndrome is associated with different ages of onset, from less than 3 months old at diagnosis to early adulthood, and is classified in different patients groups depending on their sensitivity to corticoids: ~80% of children with NS are classified as having steroid-sensitive nephrotic syndrome (SSNS) and can be successfully treated with corticosteroid therapy. A proportion of patients originally classified as SSNS relapse and need further steroid treatment, and a further 10-15% of NS patients do not achieve remission after weeks of therapy with corticosteroids and are classified as having steroid-resistant nephrotic syndrome (SRNS). Up to 50% of these SRNS patients progress to end-stage renal disease within 10 years and commonly face an elevated risk of recurrence after renal transplant. Podocyte dysfunction and resultant disruption of the glomerular filtration barrier is central to the pathogenesis of nephrotic syndrome. The podocyte branches off cellular processes to cover the outside of the glomerular capillary, called foot processes, and their interdigitations with neighbouring foot processes form the glomerular slit membrane, critical for the glomerular filtration barrier efficiency and for the retention of protein in the blood stream. In genetic forms of nephrotic syndrome, mutations in genes coding for key podocyte processes such as the development, migration, basement membrane interaction, or regeneration of the podocyte, lead to the loss of integrity of the glomerular slit membrane and to the nephrotic syndrome phenotype. Approximately 30% of cases of SRNS in children are genetic, where the most common mutations in childhood are in the NPHS2 gene, which encodes podocin, accounting for 10- 30% of sporadic genetic cases. No effective treatment currently exists for patients with nephrotic syndrome caused by mutations in NPHS2. SUMMARY OF THE INVENTION The present invention provides an AAV vector encoding podocin which demonstrates surprisingly high expression levels in podocytes and which is surprisingly able to rescue podocyte loss in a diseased podocyte adhesion assay. In one aspect, the present invention provides a polynucleotide comprising: a 5’ ITR; a kidney- specific promoter; a regulatory element comprising a spliceosomal intron or a fragment thereof comprising a branch point sequence, a polypyrimidine tract, and a 3’ splice acceptor site; a protein-coding sequence encoding podocin; and a 3’ ITR. Any suitable kidney-specific promoter may be used. In some embodiments, the kidney-specific promoter is a NPHS1 promoter. In some embodiments, the kidney-specific promoter comprises or consists of a nucleotide sequence having 80% or more, 85% or more, 90% or more, 91% or more, 92% or more, 93% or more, 94% or more, 95% or more, 96% or more, 97% or more, 98% or more, 99% or more, or 100% sequence identity to SEQ ID NO: 1. In some embodiments, the kidney-specific promoter consists of the nucleotide sequence of SEQ ID NO: 1. Any suitable regulatory element may be used. In some embodiments, the spliceosomal intron is the rabbit beta globin intron I or a variant thereof having at least 80% sequence identity thereto. In some embodiments, the regulatory element does not comprise a 5’ splice donor site. In some embodiments, the regulatory element comprises or consists of a nucleotide sequence having 80% or more, 85% or more, 90% or more, 91% or more, 92% or more, 93% or more, 94% or more, 95% or more, 96% or more, 97% or more, 98% or more, 99% or more, or 100% sequence identity to SEQ ID NO: 7. In some embodiments, the regulatory element consists of the nucleotide sequence of SEQ ID NO: 7. Any suitable podocin-coding sequence may be used. In some embodiments, the protein- coding sequence encodes an amino acid sequence having 80% or more, 85% or more, 90% or more, 91% or more, 92% or more, 93% or more, 94% or more, 95% or more, 96% or more, 97% or more, 98% or more, 99% or more, or 100% sequence identity to SEQ ID NO: 8. In some embodiments, the protein-coding sequence encodes the amino acid sequence of SEQ ID NO: 8. In some embodiments, the protein-coding sequence comprises or consists of a nucleotide sequence having 80% or more, 85% or more, 90% or more, 91% or more, 92% or more, 93% or more, 94% or more, 95% or more, 96% or more, 97% or more, 98% or more, 99% or more, or 100% sequence identity to SEQ ID NO: 9. In some embodiments, the protein- coding sequence consists of the nucleotide sequence of SEQ ID NO: 9. Any suitable ITRs may be used. In some embodiments, the 5’ ITR is an AAV25’ ITR and / or the 3’ ITR is an AAV23’ ITR. In some embodiments, the 5’ ITR is an AAV25’ ITR and the 3’ ITR is an AAV23’ ITR. In some embodiments, the 5’ ITR comprises or consists of a nucleotide sequence having 80% or more, 85% or more, 90% or more, 91% or more, 92% or more, 93% or more, 94% or more, 95% or more, 96% or more, 97% or more, 98% or more, 99% or more, or 100% sequence identity to SEQ ID NO: 52. In some embodiments, the 5’ ITR consists of the nucleotide sequence of SEQ ID NO: 52. In some embodiments, the 3’ ITR comprises or consists of a nucleotide sequence having 80% or more, 85% or more, 90% or more, 91% or more, 92% or more, 93% or more, 94% or more, 95% or more, 96% or more, 97% or more, 98% or more, 99% or more, or 100% sequence identity to SEQ ID NO: 53. In some embodiments, the 3’ ITR consists of the nucleotide sequence of SEQ ID NO: 53. In some embodiments, the polynucleotide further comprises a Woodchuck Hepatitis Virus Post-transcriptional Regulatory Element (WPRE). Any suitable WPRE may be used. In some embodiments, the WPRE comprises or consists of a nucleotide sequence having 80% or more, 85% or more, 90% or more, 91% or more, 92% or more, 93% or more, 94% or more, 95% or more, 96% or more, 97% or more, 98% or more, 99% or more, or 100% sequence identity to SEQ ID NO: 10. In some embodiments, the WPRE consists of the nucleotide sequence of SEQ ID NO: 10. In some embodiments, the polynucleotide further comprises a polyadenylation sequence. Any suitable polyadenylation sequence may be used. In some embodiments, the polyadenylation sequence is a bovine growth hormone (bGH) polyadenylation sequence. In some embodiments, the polyadenylation sequence comprises or consists of a nucleotide sequence having 80% or more, 85% or more, 90% or more, 91% or more, 92% or more, 93% or more, 94% or more, 95% or more, 96% or more, 97% or more, 98% or more, 99% or more, or 100% sequence identity to SEQ ID NO: 11. In some embodiments, the polyadenylation sequence consists of the nucleotide sequence of SEQ ID NO: 11. In some embodiments, the polynucleotide comprises from 5’ to 3’: a 5’ ITR; a kidney-specific promoter; a regulatory element comprising a spliceosomal intron or a fragment thereof comprising a branch point sequence, a polypyrimidine tract, and a 3’ splice acceptor site; a protein-coding sequence encoding podocin; optionally, a WPRE; optionally, a polyadenylation sequence; and a 3’ ITR. In some embodiments, the polynucleotide comprises: a 5’ ITR; a kidney-specific promoter consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 1; a regulatory element consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 7; a podocin coding sequence consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 9; optionally a Woodchuck Hepatitis Virus Post-transcriptional Regulatory Element (WPRE) consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 10; optionally a polyadenylation sequence consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 11; and a 3’ ITR. In some embodiments, the polynucleotide comprises: a 5’ ITR; a kidney-specific promoter consisting of a nucleotide sequence having at least 85% sequence identity to SEQ ID NO: 1; a regulatory element consisting of a nucleotide sequence having at least 85% sequence identity to SEQ ID NO: 7; a podocin coding sequence consisting of a nucleotide sequence having at least 85% sequence identity to SEQ ID NO: 9; optionally a Woodchuck Hepatitis Virus Post-transcriptional Regulatory Element (WPRE) consisting of a nucleotide sequence having at least 85% sequence identity to SEQ ID NO: 10; optionally a polyadenylation sequence consisting of a nucleotide sequence having at least 85% sequence identity to SEQ ID NO: 11; and a 3’ ITR. In some embodiments, the polynucleotide comprises: a 5’ ITR; a kidney-specific promoter consisting of a nucleotide sequence having at least 90% sequence identity to SEQ ID NO: 1; a regulatory element consisting of a nucleotide sequence having at least 90% sequence identity to SEQ ID NO: 7; a podocin coding sequence consisting of a nucleotide sequence having at least 90% sequence identity to SEQ ID NO: 9; optionally a Woodchuck Hepatitis Virus Post-transcriptional Regulatory Element (WPRE) consisting of a nucleotide sequence having at least 90% sequence identity to SEQ ID NO: 10; optionally a polyadenylation sequence consisting of a nucleotide sequence having at least 90% sequence identity to SEQ ID NO: 11; and a 3’ ITR. In some embodiments, the polynucleotide comprises: a 5’ ITR; a kidney-specific promoter consisting of a nucleotide sequence having at least 91% sequence identity to SEQ ID NO: 1; a regulatory element consisting of a nucleotide sequence having at least 91% sequence identity to SEQ ID NO: 7; a podocin coding sequence consisting of a nucleotide sequence having at least 91% sequence identity to SEQ ID NO: 9; optionally a Woodchuck Hepatitis Virus Post-transcriptional Regulatory Element (WPRE) consisting of a nucleotide sequence having at least 91% sequence identity to SEQ ID NO: 10; optionally a polyadenylation sequence consisting of a nucleotide sequence having at least 91% sequence identity to SEQ ID NO: 11; and a 3’ ITR. In some embodiments, the polynucleotide comprises: a 5’ ITR; a kidney-specific promoter consisting of a nucleotide sequence having at least 92% sequence identity to SEQ ID NO: 1; a regulatory element consisting of a nucleotide sequence having at least 92% sequence identity to SEQ ID NO: 7; a podocin coding sequence consisting of a nucleotide sequence having at least 92% sequence identity to SEQ ID NO: 9; optionally a Woodchuck Hepatitis Virus Post-transcriptional Regulatory Element (WPRE) consisting of a nucleotide sequence having at least 92% sequence identity to SEQ ID NO: 10; optionally a polyadenylation sequence consisting of a nucleotide sequence having at least 92% sequence identity to SEQ ID NO: 11; and a 3’ ITR. In some embodiments, the polynucleotide comprises: a 5’ ITR; a kidney-specific promoter consisting of a nucleotide sequence having at least 93% sequence identity to SEQ ID NO: 1; a regulatory element consisting of a nucleotide sequence having at least 93% sequence identity to SEQ ID NO: 7; a podocin coding sequence consisting of a nucleotide sequence having at least 93% sequence identity to SEQ ID NO: 9; optionally a Woodchuck Hepatitis Virus Post-transcriptional Regulatory Element (WPRE) consisting of a nucleotide sequence having at least 93% sequence identity to SEQ ID NO: 10; optionally a polyadenylation sequence consisting of a nucleotide sequence having at least 93% sequence identity to SEQ ID NO: 11; and a 3’ ITR. In some embodiments, the polynucleotide comprises: a 5’ ITR; a kidney-specific promoter consisting of a nucleotide sequence having at least 94% sequence identity to SEQ ID NO: 1; a regulatory element consisting of a nucleotide sequence having at least 94% sequence identity to SEQ ID NO: 7; a podocin coding sequence consisting of a nucleotide sequence having at least 94% sequence identity to SEQ ID NO: 9; optionally a Woodchuck Hepatitis Virus Post-transcriptional Regulatory Element (WPRE) consisting of a nucleotide sequence having at least 94% sequence identity to SEQ ID NO: 10; optionally a polyadenylation sequence consisting of a nucleotide sequence having at least 94% sequence identity to SEQ ID NO: 11; and a 3’ ITR. In some embodiments, the polynucleotide comprises: a 5’ ITR; a kidney-specific promoter consisting of a nucleotide sequence having at least 95% sequence identity to SEQ ID NO: 1; a regulatory element consisting of a nucleotide sequence having at least 95% sequence identity to SEQ ID NO: 7; a podocin coding sequence consisting of a nucleotide sequence having at least 95% sequence identity to SEQ ID NO: 9; optionally a Woodchuck Hepatitis Virus Post-transcriptional Regulatory Element (WPRE) consisting of a nucleotide sequence having at least 95% sequence identity to SEQ ID NO: 10; optionally a polyadenylation sequence consisting of a nucleotide sequence having at least 95% sequence identity to SEQ ID NO: 11; and a 3’ ITR. In some embodiments, the polynucleotide comprises: a 5’ ITR; a kidney-specific promoter consisting of a nucleotide sequence having at least 96% sequence identity to SEQ ID NO: 1; a regulatory element consisting of a nucleotide sequence having at least 96% sequence identity to SEQ ID NO: 7; a podocin coding sequence consisting of a nucleotide sequence having at least 96% sequence identity to SEQ ID NO: 9; optionally a Woodchuck Hepatitis Virus Post-transcriptional Regulatory Element (WPRE) consisting of a nucleotide sequence having at least 96% sequence identity to SEQ ID NO: 10; optionally a polyadenylation sequence consisting of a nucleotide sequence having at least 96% sequence identity to SEQ ID NO: 11; and a 3’ ITR. In some embodiments, the polynucleotide comprises: a 5’ ITR; a kidney-specific promoter consisting of a nucleotide sequence having at least 97% sequence identity to SEQ ID NO: 1; a regulatory element consisting of a nucleotide sequence having at least 97% sequence identity to SEQ ID NO: 7; a podocin coding sequence consisting of a nucleotide sequence having at least 97% sequence identity to SEQ ID NO: 9; optionally a Woodchuck Hepatitis Virus Post-transcriptional Regulatory Element (WPRE) consisting of a nucleotide sequence having at least 97% sequence identity to SEQ ID NO: 10; optionally a polyadenylation sequence consisting of a nucleotide sequence having at least 97% sequence identity to SEQ ID NO: 11; and a 3’ ITR. In some embodiments, the polynucleotide comprises: a 5’ ITR; a kidney-specific promoter consisting of a nucleotide sequence having at least 98% sequence identity to SEQ ID NO: 1; a regulatory element consisting of a nucleotide sequence having at least 98% sequence identity to SEQ ID NO: 7; a podocin coding sequence consisting of a nucleotide sequence having at least 98% sequence identity to SEQ ID NO: 9; optionally a Woodchuck Hepatitis Virus Post-transcriptional Regulatory Element (WPRE) consisting of a nucleotide sequence having at least 98% sequence identity to SEQ ID NO: 10; optionally a polyadenylation sequence consisting of a nucleotide sequence having at least 98% sequence identity to SEQ ID NO: 11; and a 3’ ITR. In some embodiments, the polynucleotide comprises: a 5’ ITR; a kidney-specific promoter consisting of a nucleotide sequence having at least 99% sequence identity to SEQ ID NO: 1; a regulatory element consisting of a nucleotide sequence having at least 99% sequence identity to SEQ ID NO: 7; a podocin coding sequence consisting of a nucleotide sequence having at least 99% sequence identity to SEQ ID NO: 9; optionally a Woodchuck Hepatitis Virus Post-transcriptional Regulatory Element (WPRE) consisting of a nucleotide sequence having at least 99% sequence identity to SEQ ID NO: 10; optionally a polyadenylation sequence consisting of a nucleotide sequence having at least 99% sequence identity to SEQ ID NO: 11; and a 3’ ITR. In some embodiments, the polynucleotide comprises: a 5’ ITR; a kidney-specific promoter consisting of a nucleotide sequence having 100% sequence identity to SEQ ID NO: 1; a regulatory element consisting of a nucleotide sequence having 100% sequence identity to SEQ ID NO: 7; a podocin coding sequence consisting of a nucleotide sequence having 100% sequence identity to SEQ ID NO: 9; optionally a Woodchuck Hepatitis Virus Post- transcriptional Regulatory Element (WPRE) consisting of a nucleotide sequence having 100% sequence identity to SEQ ID NO: 10; optionally a polyadenylation sequence consisting of a nucleotide sequence having 100% sequence identity to SEQ ID NO: 11; and a 3’ ITR. In some embodiments, the polynucleotide comprises: a 5’ ITR; a kidney-specific promoter consisting of the nucleotide sequence of SEQ ID NO: 1; a regulatory element consisting of the nucleotide sequence having of SEQ ID NO: 7; a podocin coding sequence consisting of the nucleotide sequence of SEQ ID NO: 9; optionally a Woodchuck Hepatitis Virus Post- transcriptional Regulatory Element (WPRE) consisting of the nucleotide sequence of SEQ ID NO: 10; optionally a polyadenylation sequence consisting of the nucleotide sequence of SEQ ID NO: 11; and a 3’ ITR. In another aspect, the present invention provides a polynucleotide comprising a nucleotide sequence having at least 70% sequence identity to SEQ ID NO: 34. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 80% identical to SEQ ID NO: 34. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 85% identical to SEQ ID NO: 34. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 90% identical to SEQ ID NO: 34. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 95% identical to SEQ ID NO: 34. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 98% identical to SEQ ID NO: 34. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 99% identical to SEQ ID NO: 34. In some embodiments, the polynucleotide comprises the nucleotide sequence SEQ ID NO: 34. In another aspect, the present invention provides a polynucleotide comprising or consisting of a nucleotide sequence having at least 70% sequence identity to SEQ ID NO: 54. In some embodiments, the polynucleotide comprises or consists of a nucleotide sequence which is at least 80% identical to SEQ ID NO: 54. In some embodiments, the polynucleotide comprises or consists of a nucleotide sequence which is at least 85% identical to SEQ ID NO: 54. In some embodiments, the polynucleotide comprises or consists of a nucleotide sequence which is at least 90% identical to SEQ ID NO: 54. In some embodiments, the polynucleotide comprises or consists of a nucleotide sequence which is at least 95% identical to SEQ ID NO: 54. In some embodiments, the polynucleotide comprises or consists of a nucleotide sequence which is at least 98% identical to SEQ ID NO: 54. In some embodiments, the polynucleotide comprises or consists of a nucleotide sequence which is at least 99% identical to SEQ ID NO: 54. In some embodiments, the polynucleotide comprises or consists of the nucleotide sequence SEQ ID NO: 54. In another aspect, the present invention provides an AAV vector comprising the polynucleotide of the present invention. In another aspect, the present invention provides an AAV vector particle comprising the polynucleotide of the present invention. The AAV vector particle may be encapsidated by any suitable capsid proteins. In some embodiments, the AAV vector particle is encapsidated by LK03, AAV3B, AAV9, ShH10, AAV- DJ, AAV2, AAV6.2, or AAV5 capsid proteins. In some embodiments, the AAV vector particle is encapsidated by LK03 capsid proteins. In some embodiments, the AAV vector particle is encapsidated by capsid proteins having 95% or more, 96% or more, 97% or more, 98% or more, 99% or more, or 100% sequence identity to SEQ ID NO: 36. In some embodiments, the AAV vector particle is encapsidated by capsid proteins consisting of the amino acid sequence of SEQ ID NO: 36. In another aspect, the present invention provides a pharmaceutical composition comprising the polynucleotide of the present invention, the AAV vector of the present invention, or the AAV vector particle of the present invention, and a pharmaceutically acceptable carrier, diluent and / or excipient. In another aspect, the present invention provides a polynucleotide of the present invention, an AAV vector of the present invention, an AAV vector particle of the present invention, or a pharmaceutical composition of the present invention, for use as a medicament. In another aspect, the present invention provides use of a polynucleotide of the present invention, an AAV vector of the present invention, an AAV vector particle of the present invention, or a pharmaceutical composition of the present invention, for the manufacture of a medicament. In another aspect, the present invention provides a polynucleotide of the present invention, an AAV vector of the present invention, an AAV vector particle of the present invention, or a pharmaceutical composition of the present invention, for use in treating nephrotic syndrome. In another aspect, the present invention provides use of a polynucleotide of the present invention, an AAV vector of the present invention, an AAV vector particle of the present invention, or a pharmaceutical composition of the present invention, for the manufacture of a medicament for treating nephrotic syndrome. In another aspect, the present invention provides a method of treating nephrotic syndrome, the method comprising administering a polynucleotide of the present invention, an AAV vector of the present invention, an AAV vector particle of the present invention, or a pharmaceutical composition of the present invention, to a subject in need thereof. The nephrotic syndrome may be steroid-resistant nephrotic syndrome (SRNS). The nephrotic syndrome may be genetic steroid-resistant nephrotic syndrome (SRNS). The nephrotic syndrome may be caused by one or more mutations in NPHS2, or in the promoter or regulatory regions upstream of NPHS2. The AAV vector, AAV vector particle, or pharmaceutical composition may be administered by any suitable route and in any suitable dosage. Suitably, the AAV vector, AAV vector particle, or pharmaceutical composition is administered by renal artery injection, by intraparenchymal injection, by transparenchymal injection, by renal vein injection, by ureteral injection, or by subcapsular injection. In some embodiments, the AAV vector, AAV vector particle, or pharmaceutical composition is administered by renal artery injection. Suitably, the AAV vector, AAV vector particle, or pharmaceutical composition is administered in a dose of from about 1x106vg / kg to about 1x1014vg / kg. In another aspect, the present invention provides a vector comprising the polynucleotide of the present invention. Suitably, the vector is a plasmid. In another aspect, the present invention provides a kit for production of AAV vector particles comprising, a vector of the present invention, and one or more helper plasmids encoding AAV replication and capsid proteins. In another aspect, the present invention provides an isolated cell comprising the polynucleotide of the present invention, the AAV vector of the present invention, the AAV vector particle of the present invention, or the vector of the present invention. Suitably, the cell is a packaging cell. DESCRIPTION OF DRAWINGS Figure 1 – Expression of luciferase in HEK 293T cells in the presence or absence of RBG intron I (A) Schematic of constructs tested. (B) Luciferase expression in HEK 293T cells by luciferase assay two days post-transfection. Figure 2 – Expression of podocin in podocytes and rescue of detachment in diseased podocytes in the presence or absence of RBG intron I (A) Schematic of AAV genomes tested. (B-E) Podocin expression quantification by ELISA after 10 days of differentiation and transduction in: (B) healthy podocytes at a multiplicity of infection of 1e5 vg / cell; (C) R138Q patient podocytes at a multiplicity of infection of 1e5 vg / cell; (D) R138Q patient podocytes at a multiplicity of infection of 5e4 vg / cell; and (E) R138Q patient podocytes at a multiplicity of infection of 1e4 vg / cell. (F-H) Rescue of detachment in diseased podocytes transduced with AAV at a multiplicity of infection of: (F) 1e5 vg / cell, (G) 5e4 vg / cell, or (H) 1e4 vg / cell. Figure 3 – Expression of podocin in podocytes and rescue of detachment in diseased podocytes using a CMV promoter (A) Podocin expression quantification by ELISA in healthy podocytes. (B) Podocin expression quantification by ELISA in R138Q patient podocytes. (C) Rescue of detachment in diseased podocytes transduced with AAV. (D) Schematic of AAV genome: CMV-podocin. Figure 4 – Expression reporter transgenes in HEK AD293 cells in the presence or absence of RBG intron I HEK AD293 cells were transfected with 2 µg of DNA plasmid and cultured in serum-free medium for 72h for supernatant collection. Samples were analysed by immunoblot, by incubating the membranes with anti-HA primary antibody (Cell Signalling) and anti-rabbit IgG HRP secondary antibody (Sigma). (A) Immunoblots showing supernatant from non-treated cells (NT) and from cells transfected with plasmid containing RBG-reporter1 vs reporter1 (n=2 independent biological replicates). (B) Immunoblots showing supernatant from non-treated cells (NT) and from cells transfected with plasmid containing RBG-reporter2 vs reporter2 (n=2 independent biological replicates). (C) Immunoblots showing supernatant from non-treated cells (NT) and from cells transfected with plasmid containing RBG-reporter3 vs reporter2 (n=2 independent biological replicates). Ladder = Molecular weight markers; NT = non-transfected cells; RBG.reporter1 = cells transfected with NPHS1(265)-RBG-reporter1 plasmid; reporter1 = cells transfected with NPHS1(265)-reporter1 plasmid; RBG.reporter2 = cells transfected with NPHS1(265)-RBG-reporter2 plasmid; reporter2 = cells transfected with NPHS1(265)- reporter2 plasmid; RBG.reporter3 = cells transfected with NPHS1(265)-RBG-reporter3 plasmid; reporter3 = cells transfected with NPHS1(265)-reporter3 plasmid. Figure 5 – Expression of reporter transgenes in human podocytes in the presence or absence of RBG intron I Human podocytes were transduced with LK03 AAV vectors at MOI 1e5 vg / cell and cultured in serum-free medium for 72h for supernatant collection. Samples were analysed by immunoblot, by incubating the membranes with anti-HA primary antibody (Cell Signalling) and anti-rabbit IgG HRP secondary antibody (Sigma) or by ELISA. (A) Representative immunoblot showing supernatant from non-treated cells (NT) and from podocytes transduced with LK03- NPHS1(265)-RBG-reporter1 vs LK03-NPHS1(265)-reporter1, and LK03-NPHS1(265)-RBG- reporter2 vs LK03-NPHS1(265)-reporter2 (n=2 independent biological replicates). (B) Reporter transgene protein quantified by ELISA in supernatant from non-treated cells (NT) and from podocytes transduced with LK03-NPHS1(265)-RBG-reporter1 vs LK03- NPHS1(265)-reporter1 (n=2 independent biological replicates). Ladder = Molecular weight markers; NT = non-transduced cells; RGB.reporter1 = cells transduced with LK03- NPHS1(265)-RGB-reporter1 AAV vector; reporter1 = cells transduced with LK03- NPHS1(265)-reporter1 AAV vector; RGB.reporter3 = cells transduced with LK03- NPHS1(265)-RGB-reporter3 AAV vector; reporter3 = cells transduced with LK03- NPHS1(265)-reporter3 AAV vector. Figure 6 – Expression of reporter transgene in wild-type mice in the presence or absence of RBG intron I The kidneys were collected 2 weeks upon intravenous injection of mice with AAV9- NPHS1(265)-reporter3 or AAV9-NPHS1(265)-RBG-reporter3 vectors at 1.5e12 vg / mouse and the level of gene expression determined by (A) RNA RT-qPCR or (B) DNA qPCR. For both the analyses, a probe targeting WPRE was used to measure AAV genomic DNA or RNA in tissue lysates. Data are represented as copies per µg of genomic RNA or DNA. Each dot represents a mouse and is the result of the mean of 2 technical replicates. Data are shown as mean ± standard deviation (SD). (C) Graph representing the reporter transgene protein quantification by ELISA in kidney at 2, 5 and 9 weeks upon delivery of AAV vectors into the tail vein of wild-type mice (1.5e12 vg / mouse). The graph shows the mean of duplicates run in the ELISA, and each dot represents a mouse. The results were interpolated using sigmoidal, 4PL analysis. Data are represented as ng of protein per µg of total protein and shown as mean ± SEM. DETAILED DESCRIPTION Various preferred features and embodiments of the present invention will now be described by way of non-limiting examples. This disclosure is not limited by the exemplary methods and materials disclosed herein, and any methods and materials similar or equivalent to those described herein can be used in the practice or testing of embodiments of this disclosure. The skilled person will understand that they can combine all features of the invention disclosed herein without departing from the scope of the invention as disclosed. It must be noted that as used herein and in the appended claims, the singular forms "a", "an", and "the" include plural referents unless the context clearly dictates otherwise. The terms "comprising", "comprises" and "comprised of" as used herein are synonymous with "including", "includes", "containing", or "contains", and are inclusive or open-ended and do not exclude additional, non-recited members, elements or steps. The terms "comprising", "comprises" and "comprised of" also include the term "consisting of". Numeric ranges are inclusive of the numbers defining the range. As used herein the term “about” means approximately, in the region of, roughly, or around. When the term “about” is used in conjunction with a numerical value or range, it modifies that value or range by extending the boundaries above and below the numerical value(s) set forth. In general, the terms “about” and “approximately” may be used herein to modify a numerical value(s) above and below the stated value(s) by 10%. Unless otherwise indicated, any nucleic acid sequences are written left to right in 5' to 3' orientation; amino acid sequences are written left to right in amino to carboxy orientation, respectively. The publications discussed herein are provided solely for their disclosure prior to the filing date of the present application. Nothing herein is to be construed as an admission that such publications constitute prior art to the claims appended hereto. All publications mentioned in the specification are herein incorporated by reference. Polynucleotides In one aspect, the present invention provides a polynucleotide comprising: a 5’ ITR; a kidney- specific promoter; a regulatory element comprising a spliceosomal intron or a fragment thereof comprising a branch point sequence, a polypyrimidine tract, and a 3’ splice acceptor site; a protein-coding sequence encoding podocin; and a 3’ ITR. In some embodiments, the polynucleotide comprises from 5’ to 3’: a 5’ ITR; a kidney-specific promoter; a regulatory element comprising a spliceosomal intron or a fragment thereof comprising a branch point sequence, a polypyrimidine tract, and a 3’ splice acceptor site; a protein-coding sequence encoding podocin; and a 3’ ITR. The polynucleotide of the invention may be an isolated polynucleotide. The polynucleotide of the invention may comprise or consist of DNA and / or RNA (e.g. wherein “T” is replaced by “U” as appropriate). Preferably, the polynucleotide of the invention consists of DNA. Suitably, the polynucleotide of the invention may be limited to a size suitable to be inserted into an adeno-associated viral (AAV) vector. Suitably, the polynucleotide of the invention may be 5.0 kb or less, 4.9 kb or less, 4.8 kb or less, 4.7 kb or less in total length. In some embodiments, the polynucleotide of the invention is 4.7 kb or less in total length. Suitably, the polynucleotide of the invention may be 4.0 kb or more, 4.1 kb or more, 4.2 kb or more, 4.3 kb or more, 4.4 kb or more, 4.5 kb or more, or 4.6 kb or more in total length. In some embodiments, the polynucleotide of the invention is from 4.0 kb to 4.7 kb, from 4.1 kb to 4.7 kb, from 4.2 kb to 4.7 kb, from 4.3 kb to 4.7 kb, from 4.4 kb to 4.7 kb, from 4.5 kb to 4.7 kb, or from 4.6 kb to 4.7 kb in total length. Promoters The polynucleotide of the present invention further comprises a kidney-specific promoter. The kidney-specific promoter may be operably linked to the protein-coding sequence. A “promoter” is a region of DNA that leads to initiation of transcription of a gene. Promoters are located near the transcription start sites of genes, upstream on the DNA (towards the 5' region of the sense strand). As used herein, a “tissue-specific promoter” is a promoter which preferentially facilitates expression of a protein-coding sequence in a specific type of cells or tissue. Suitably, a tissue- specific promoter may facilitate higher expression of a protein-coding sequence in one cell- type as compared to other cell-types. For example, a tissue-specific promoter may be a promoter which facilitates expression of a protein-coding sequence at least 10% higher, at least 20% higher, at least 30% higher, at least 40% higher, at least 50% higher, at least 100% higher, at least 200% higher, at least 300% higher, at least 400% higher, at least 500% higher, or at least 1000% higher in one cell-type as compared to expression in other cell-types. Suitable tissue-specific promoters will be known to the skilled person. Any suitable kidney-specific promoter may be used, the selection of which may be readily made by the skilled person. Suitably, the kidney-specific promoter may be or may be derived from a promoter associated with a gene with selective expression in human kidneys. Genes selectively expressed in the kidney will be known to those of skill in the art and selective gene expression in podocytes can be readily determined by methods know to those of skill in the art, for instance with microarrays. For example, genes selectively expressed in podocytes include NPHS1, NPHS2, WT1, FOXC2, ABCA9, ACPP, ACTN4, ADM, ANGPTL2, ANXA1, ASB15, ATP8B1, B3GALT2, BB014433, BMP7, C1QTNF1, CAR13, CD2AP, CD55, CD59A, CD59B, CDC14A, CDH3, CDKN1B, CDKN1C, CEP85L, CLIC3, CLIC5, COL4A1, COL4A2, COL4A3, COL4A4, COL4A5, COLEC12, CRIM1, CST12, DEGS1, DOCK4, DOCK5, EGF, ENPEP, EPHX1, FAM81A, FAT1, FGFBP1, FOXD1, FRYL, GABRB1, GALC, GM10554, H2-D1, H2-Q7, H2BC4, H3C15, HS3ST3A1, HTRA1, IFNGR1, IL18, ILDR2, ITGB5, ITGB8, KIRREL, LAMA1, LAMA5, LAMB1, LAMB2, LMX1B, MAFB, MAGI2, MELA, MERTK, MGAT4A, MYO1D, MYO1E, MYOM2, MYZAP, NEBL, NES, NOD1, NPR3, NR2F2, NUPR1, OPTN, P3H2, PAK1, PARD3B, PDPN, PLAT, PLCE1, PLSCR2, PODXL, PROS1, PTPRO, RAB3B, RDH1, RDH9, SDC4, SEMA3E, SERPINB6B, SH3BGRL2, SLC41A2, SLCO2A1, ST3GAL6, SYNPO, TDRD5, THSD7A, TIMP3, TJP1, TLR7, TM4SF1, TMEM108, TMEM54, TMTC1, TOP1MT, TRAV10, TRAV10N, TRAV5-4, TSHB, UACA, UBA1Y, UPRT, VEGFA, VTCN1, ZBTB20, and 5730407I07RIK. Methods to identify the promoter regions associated with genes will be well known to those of skill in the art. The promoter is usually located just proximal to or overlapping the transcription initiation site and contains several sequence motifs with which transcription factors (TFs) interact in a sequence-specific manner. In some embodiments, the kidney-specific promoter is a glomerular-specific promoter. In preferred embodiments, the kidney-specific promoter is a podocyte-specific promoter. Suitably, the kidney-specific promoter is selected from a NPHS1 promoter, a NPHS2 promoter, a WT1 promoter, a FOXC2 promoter, a ABCA9 promoter, a ACPP promoter, a ACTN4 promoter, a ADM promoter, a ANGPTL2 promoter, a ANXA1 promoter, a ASB15 promoter, a ATP8B1 promoter, a B3GALT2 promoter, a BB014433 promoter, a BMP7 promoter, a C1QTNF1 promoter, a CAR13 promoter, a CD2AP promoter, a CD55 promoter, a CD59A promoter, a CD59B promoter, a CDC14A promoter, a CDH3 promoter, a CDKN1B promoter, a CDKN1C promoter, a CEP85L promoter, a CLIC3 promoter, a CLIC5 promoter, a COL4A1 promoter, a COL4A2 promoter, a COL4A3 promoter, a COL4A4 promoter, a COL4A5 promoter, a COLEC12 promoter, a CRIM1 promoter, a CST12 promoter, a DEGS1 promoter, a DOCK4 promoter, a DOCK5 promoter, a EGF promoter, a ENPEP promoter, a EPHX1 promoter, a FAM81A promoter, a FAT1 promoter, a FGFBP1 promoter, a FOXD1 promoter, a FRYL promoter, a GABRB1 promoter, a GALC promoter, a GM10554 promoter, a H2-D1 promoter, a H2-Q7 promoter, a H2BC4 promoter, a H3C15 promoter, a HS3ST3A1 promoter, a HTRA1 promoter, a IFNGR1 promoter, a IL18 promoter, a ILDR2 promoter, a ITGB5 promoter, a ITGB8 promoter, a KIRREL promoter, a LAMA1 promoter, a LAMA5 promoter, a LAMB1 promoter, a LAMB2 promoter, a LMX1B promoter, a MAFB promoter, a MAGI2 promoter, a MELA promoter, a MERTK promoter, a MGAT4A promoter, a MYO1D promoter, a MYO1E promoter, a MYOM2 promoter, a MYZAP promoter, a NEBL promoter, a NES promoter, a NOD1 promoter, a NPR3 promoter, a NR2F2 promoter, a NUPR1 promoter, a OPTN promoter, a P3H2 promoter, a PAK1 promoter, a PARD3B promoter, a PDPN promoter, a PLAT promoter, a PLCE1 promoter, a PLSCR2 promoter, a PODXL promoter, a PROS1 promoter, a PTPRO promoter, a RAB3B promoter, a RDH1 promoter, a RDH9 promoter, a SDC4 promoter, a SEMA3E promoter, a SERPINB6B promoter, a SH3BGRL2 promoter, a SLC41A2 promoter, a SLCO2A1 promoter, a ST3GAL6 promoter, a SYNPO promoter, a TDRD5 promoter, a THSD7A promoter, a TIMP3 promoter, a TJP1 promoter, a TLR7 promoter, a TM4SF1 promoter, a TMEM108 promoter, a TMEM54 promoter, a TMTC1 promoter, a TOP1MT promoter, a TRAV10 promoter, a TRAV10N promoter, a TRAV5-4 promoter, a TSHB promoter, a UACA promoter, a UBA1Y promoter, a UPRT promoter, a VEGFA promoter, a VTCN1 promoter, a ZBTB20 promoter, and a 5730407I07RIK promoter, or a variant thereof. Suitably, the kidney-specific promoter is selected from a NPHS1 promoter, a NPHS2 promoter, a WT1 promoter, a FOXC2 promoter, a ACTN4 promoter, a BMP7 promoter, a CD2AP promoter, a CDH3 promoter, a CDKN1B promoter, a CDKN1C promoter, a COL4A1 promoter, a COL4A2 promoter, a COL4A3 promoter, a COL4A4 promoter, a COL4A5 promoter, a CRIM1 promoter, a FAT1 promoter, a FOXD1 promoter, a KIRREL promoter, a LAMA1 promoter, a LAMA5 promoter, a LAMB1 promoter, a LAMB2 promoter, a LMX1B promoter, a MAFB promoter, a NES promoter, a NR2F2 promoter, a PODXL promoter, a PTPRO promoter, a SYNPO promoter, a TJP1 promoter, and a VEGFA promoter, or a variant thereof. Suitably, the kidney-specific promoter is a NPHS1 promoter, a NPHS2 promoter, a WT1 promoter, or a FOXC2 promoter, or a variant thereof. Suitably, the kidney-specific promoter is a NPHS1 or a NPHS2 promoter, or a variant thereof. In preferred embodiments, the kidney-specific promoter is a NPHS1 promoter, or a variant thereof. In other preferred embodiments, the kidney-specific promoter is a NPHS1 promoter. Preferably, the promoter is a human promoter, e.g. a human NPHS1 promoter. The kidney-specific promoter may be a minimal kidney-specific promoter. As used, herein, a “minimal kidney-specific promoter” means the minimal sequence that can act as a kidney- specific promoter. In some embodiments, the kidney-specific promoter is a minimal glomerular-specific promoter. In some embodiments, the kidney-specific promoter is a minimal podocyte-specific promoter. Suitably, the kidney-specific promoter is a minimal NPHS1 or a minimal NPHS2 promoter, or a variant thereof. NPHS1 promoter In some embodiments, the kidney-specific promoter is a NPHS1 promoter, or a variant thereof. In some embodiments, the kidney-specific promoter is a NPHS1 promoter. The NPHS1 gene encodes nephrin, which is selectively expressed in podocytes. A human NPHS1 promoter has been described in Moeller et al.2002 J Am Soc Nephrol, 13(6):1561–7 and Wong MA et al. 2000 Am J Physiol Renal Physiol, 279(6):F1027-32. This NPHS1 promoter is a 1.2kb fragment and appears to be podocyte-specific. The 1.2kb promoter region lacks a TATA box, but has recognition motifs for other transcription factors e.g. PAX-2 binding element, E-box and GATA consensus sequences. In some embodiments, the NPHS1 promoter comprises or consists of the nucleotide sequence shown as SEQ ID NO: 1, or a variant which is at least 70% identical to SEQ ID NO: 1. Suitably, the variant may be at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 1. In some embodiments, the NPHS1 promoter comprises or consists of the nucleotide sequence shown as SEQ ID NO: 1. In some embodiments, the NPHS1 promoter consists of the nucleotide sequence shown as SEQ ID NO: 1, or a variant which is at least 70% identical to SEQ ID NO: 1. Suitably, the variant may be at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 1. In preferred embodiments, the NPHS1 promoter consists of the nucleotide sequence shown as SEQ ID NO: 1. cacctgaggtcaggagttcgagaccagcgtggccaacatgatgaaaccccgtctctagtaaa aatacaaaaattagccaggcatggtgctatatacctgtagcaccagctacttgggagacaga ggtgggagaattacttgaacctgggaggttcaagccatgggaggtggaagttgcagtgagcc gagatgccactgcactccagcctgagcaacagagcaagactatctcaagaaaagaaagaaag aaagaaagagacttgccaaggtcatgtatcagggcaaggaagagctgggggcccagctggct gctcccctgctgagctgggagaccaccttgatctgacttctcccatcttcccagcctaagcc aggccctggggtcacggaggctggggaggcaccgaggaacgcgcctggcatgtgctgacagg ggattttatgctccagctgggccagctgggaggagcctgctgggcagaggccagagctgggg gctctggaaggtacctgggggaggttgcactgtgagaatgagctcaagctgggtcagagagc agggctgactctgccagtgcctgcatcagcctcatcgctctcctaggctcctggcctgctgg actctgggctgcaggtccttcttgaaaggctgtgagtagtgagacaaggagcaggagtgagg ggtggcaggagagaagatagagattgagagagagagagagagagagacagagagagaggaag agacagagacaaaaggagagagaacggcttagacaaggagagaaagatggaaagataaagag actgggcgcagtggctcacgcctgtaatcccaacacttggggaggccaaggtgggaggatgg cttgaaggaaagagtctgagatcaacctggccaacatagtgagaccccgtctctaaaaaaaa aagaaaaaaaaaagaaaaaagaaaaaaaagtttttttaaagagacagagaaagagactcaga gattgagactgagagcaagacagagagagatactcacagggaagaggggaagaggaaaacga gaaagggaggagagtaacggaaagagataaaaaagaaaagcaggtggcagagacacacagag agggacccagagaaagccagacagacgcaggtggctggcagcgggcgctgtgggggtcacag tagggggacctgtg Example NPHS1 promoter (SEQ ID NO: 1) Regulatory elements The polynucleotide of the present invention further comprises a regulatory element comprising a spliceosomal intron or a fragment thereof comprising a branch point sequence, a polypyrimidine tract, and a 3’ splice acceptor site. The regulatory element may be operably linked to the protein-coding sequence. A “regulatory element” may refer to any sequence which increases expression of a protein- coding sequence, e.g. which acts to increase expression of a transcript or to enhance mRNA stability. Suitably, the regulatory element may act post-transcriptionally (i.e. is a post- transcriptional regulatory element). Suitably, the regulatory element may enhance mRNA stability. The regulatory element may, in particular, be capable of increasing expression of a protein- coding sequence downstream thereof. The regulatory element may be a 5’UTR regulatory element. A “5’UTR regulatory element” may refer to a sequence which increases expression of a protein-coding sequence downstream thereof. Suitably, the regulatory element is operable in mammalian cells, e.g. human cells. The regulatory element may be capable of increasing expression of a protein-coding sequence in mammalian cells, e.g. human cells. The regulatory element may be a mammalian regulatory element. The regulatory element may be operable in kidney cells. The regulatory element may be capable of increasing expression of a protein-coding sequence in the kidney. Examples of kidney cells include, but are not limited, to glomerular cells. The regulatory element may be operable in glomerular cells. The regulatory element may be capable of increasing expression of a protein-coding sequence in the glomerulus. The regulatory element may be operable in a podocyte cell. The regulatory element may be capable of increasing expression of a protein- coding sequence in podocytes. Expression of a protein-coding sequence may be measured by any suitable method known in the art. For example by measuring the expression of a reporter transgene, e.g. Luciferase, placed downstream of the regulatory element, wherein expression of the reporter transgene correlates with the ability of the regulatory element to increase expression of a protein-coding sequence. Expression of the reporter transgene, e.g. Luciferase may be determined by any suitable method. Suitable cell lines will be well known to those of skill in the art. For example, a suitable podocyte cell line is CIHP-1 and methods to generate immortalized podocytes will be well known to those of skill in the art (see e.g. Ni, L., et al., 2012. Nephrology, 17(6), pp.525- 531). Spliceosomal introns A “spliceosomal intron” may refer to a non-coding sequence excised from pre-mRNAs by the spliceosome during mRNA splicing. Spliceosomal introns have been found in most eukaryotic genes and their lengths vary between species, from just tens of bases in some protists to hundreds of kilobases in some mammals (see e.g. Roy, S. W. and Gilbert, W., 2006. Nature Reviews Genetics, 7(3), pp.211-221). The spliceosomal intron may be a naturally-occurring spliceosomal intron, a chimeric spliceosomal intron (e.g. with elements derived from two or more naturally-occurring spliceosomal introns), or a variant spliceosomal intron. Examples of suitable naturally-occurring spliceosomal introns include the rabbit beta globin intron I, the rabbit beta globin intron II, the minute virus of mice (MVM) intron, and the F.IX truncated intron 1. Examples of suitable chimeric spliceosomal introns include β-globin SD / immunoglobin heavy chain SA, Adenovirus SD / immunoglobulin SA, SV40 late SD / SA (19S / 16S), and Hybrid adenovirus SD / IgG SA (see e.g. Powell, S.K., et al., 2015. Discovery medicine, 19(102), pp.49-57). Examples of suitable variant spliceosomal introns are described below. A spliceosomal intron typically contains the following conserved elements from 5’ to 3’: a 5’ splice donor site, also known as a 5’ splice site; a branch point sequence, comprising the branch point; a polypyrimidine tract; and a 3’ splice acceptor site, also known as a 3’ splice site (see e.g. Padgett, R.A., et al., 1986. Annual review of biochemistry, 55(1), pp.1119-1150). In human spliceosomal introns, the human branch point consensus sequence is yUnAy, where the branch point ‘A’ is underlined. Branch points are typically located 21–34 nucleotides upstream of the 3′ end of an intron. A polypyrimidine stretch typically spans 4–24 nucleotides downstream of the branch point (see e.g. Gao, K., et al., 2008. Nucleic acids research, 36(7), pp.2257-2267). The spliceosomal intron may comprise each of the 5’ splice donor site, the branch point sequence, the polypyrimidine tract, and the 3’ splice acceptor site in consensus positions. Suitably, the 5’ splice donor site is from about 10 bp to about 1000 bp upstream of the branch point or from about 50 bp to about 100 bp upstream of the branch point. Suitably, the polypyrimidine tract is from about 4 bp to about 24 bp downstream of the branch point. Suitably, the 3’ splice point is from about 21 bp to about 34 bp downstream of the branch point. The spliceosomal intron may comprise a consensus 5’ splice donor site, a consensus branch point sequence, a consensus polypyrimidine tract, and / or a consensus 3’ splice acceptor site. In some embodiments, the spliceosomal intron comprises at least a consensus branch point sequence and a consensus 3’ splice acceptor site. Suitably, a consensus 5’ splice donor site comprises or consists of the nucleotide sequence GTRAGT. Suitably, a consensus branch point sequence comprises or consists of the nucleotide sequence YTNAY. In some embodiments, the branch point sequence comprises or consists of the nucleotide sequence TGCTGAC. Suitably, a consensus polypyrimidine tract comprises or consists of (Y)n2, where n2 is from about 10 to about 20. Suitably, a consensus 3’ splice acceptor site comprises or consists of the nucleotide sequence YAGG. Suitably, the spliceosomal intron has a length of about 1000 bp or less, about 900 bp or less, about 800 bp or less, about 700 bp or less, about 600 bp or less, about 500 bp or less, about 400 bp or less, about 300 bp or less, about 200 bp or less, about 150 bp or less, about 140 bp or less, or about 130 bp or less. Suitably, the spliceosomal intron has a length of about 40 bp or more, about 50 bp or more, about 60 bp or more, about 70 bp or more, about 80 bp or more, about 90 bp or more, about 100 bp or more, about 100 bp or more, about 105 bp or more, about 110 bp or more, about 115 bp or more, or about 120 bp or more. Suitably, the spliceosomal intron has a length of from about 100 bp to about 1000 bp, from about 100 bp to about 900 bp, from about 100 bp to about 800 bp, from about 100 bp to about 700 bp, from about 100 bp to about 600 bp, from about 100 bp to about 500 bp, from about 100 bp to about 400 bp, from about 100 bp to about 300 bp, from about 100 bp to about 200 bp, or from about 100 bp to about 150 bp. Suitably, the spliceosomal intron may comprise or consist of the nucleotide sequence GTRAGT(N)xYTNAY(N)n1(Y)n2(N)n3YAGG, wherein x is from about 10 to about 1000 (e.g. from about 10 to about 100), n1 is from about 2 to about 22, n2 is from about 10 to about 20, and n1 + n2 + n3 is from about 15 to about 40, or a nucleotide sequence having five or fewer, four or fewer, three or fewer, two or fewer, or one nucleotide substitution. Variant spliceosomal introns A variant spliceosomal intron may be derived from any naturally-occurring or chimeric spliceosomal intron, referred to herein as the “wild-type spliceosomal intron”. Suitably, a variant spliceosomal intron may have 70% or more, 75% or more, 80% or more, 81% or more, 82% or more, 83% or more, 84% or more, 85% or more, 86% or more, 87% or more, 88% or more, 89% or more, 90% or more, 91% or more, 92% or more, 93% or more, 94% or more, 95% or more, 96% or more, 97% or more, 98% or more, 99% or more, or 100% sequence identity to a wild-type spliceosomal intron. A variant spliceosomal intron may be obtained by substituting, inserting, and / or deleting 20 or fewer, 15 or fewer, 10 or fewer, 9 or fewer, 8 or fewer, 7 or fewer, 6 or fewer, 5 or fewer, 4 or fewer, 3 or fewer, 2 or fewer, or 1 nucleotide(s) into the wild-type spliceosomal intron. A variant spliceosomal intron may be obtained by substituting 10 or fewer, 9 or fewer, 8 or fewer, 7 or fewer, 6 or fewer, 5 or fewer, 4 or fewer, 3 or fewer, 2 or fewer, or 1 nucleotide(s) of the wild- type spliceosomal intron. A variant spliceosomal intron may be obtained by inserting 20 or fewer, 15 or fewer, 10 or fewer, 9 or fewer, 8 or fewer, 7 or fewer, 6 or fewer, 5 or fewer, 4 or fewer, 3 or fewer, 2 or fewer, or 1 nucleotide(s) into the wild-type spliceosomal intron. A variant spliceosomal intron may be obtained by deleting 20 or fewer, 15 or fewer, 10 or fewer, 9 or fewer, 8 or fewer, 7 or fewer, 6 or fewer, 5 or fewer, 4 or fewer, 3 or fewer, 2 or fewer, or 1 nucleotide(s) from the wild-type spliceosomal intron. In some embodiments, a variant spliceosomal intron has 5 or fewer, 4 or fewer, 3 or fewer, 2 or fewer, or 1 nucleotide substitution(s) compared to a wild-type spliceosomal intron. Suitably, a variant spliceosomal intron retains or improves the wild-type spliceosomal introns ability to increase expression of a protein-coding sequence. Expression of a protein-coding sequence may be measured by any suitable method known in the art. For example, by measuring the expression of a reporter transgene, e.g. Luciferase, placed downstream of the spliceosomal intron, wherein expression of the reporter transgene correlates with the ability of the spliceosomal intron to increase expression of a protein-coding sequence. Suitably, the variant spliceosomal intron increases expression of a protein-coding sequence to at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or at least 100% of the level of the wild- type spliceosomal intron. Suitably, a wild-type spliceosomal intron may be modified to increase (or decrease) the consensus, to insert further nucleotide sequences, and / or to delete nucleotide sequences which are not required for the spliceosomal intron to increase expression of a protein-coding sequence. In some embodiments, the wild-type spliceosomal intron is modified to increase the consensus. Suitably, a variant spliceosomal intron may be obtained by modifying the wild-type spliceosomal intron to increase the consensus. Suitably, the 5’ splice donor site may be altered to consist of the consensus sequence GTRAGT; the branch point sequence may be altered to consist of the consensus sequence YTNAY; the polypyrimidine tract may be altered to consist of (Y)n2, where n2 is from about 10 to about 20; and / or the 3’ splice acceptor site may be altered to consist of YAGG. In some embodiments, the branch point sequence is altered to consist of the nucleotide sequence TGCTGAC. In some embodiments, the polypyrimidine tract is altered to consist of the nucleotide sequence (Y)n2, where n2 is from about 10 to about 20. Alternatively (or additionally), a variant spliceosomal intron may be obtained by modifying the wild-type spliceosomal intron to decrease the consensus, e.g. by making five or fewer, four or fewer, three or fewer, two or fewer, or one or fewer nucleotide substitution. In particular, the 5’ splice donor site and / or polypyrimidine tract may each be modified by making one or more nucleotide substitution. Such a modification may be made without affecting the ability of the spliceosomal intron to increase expression of a protein-coding sequence. Suitably, a variant spliceosomal intron may be obtained by modifying the wild-type spliceosomal intron to insert and / or delete nucleotide sequences such that the polypyrimidine tract and / or the 3’ splice acceptor site are in consensus positions. Suitably, one or more nucleotides sequences are inserted and / or deleted such that the polypyrimidine tract is about 4 to about 24 bp downstream of the branch point. Suitably, one or more nucleotides sequences are inserted and / or deleted such that the 3’ splice point is from about 21 to about 34 bp downstream of the branch point. Suitably, a variant spliceosomal intron may be obtained by modifying the wild-type spliceosomal intron to insert nucleotide sequences. For example, one or more nucleotide sequences (e.g. one or more restriction site) may be introduced upstream of the branch point sequence without affecting the ability of the spliceosomal intron to increase expression of a protein-coding sequence. Suitably, the insertion is about 100 bp or less, about 50 bp or less, about 45 bp or less, about 40 bp or less, about 40 bp or less, about 35 bp or less, about 30 bp or less, about 25 bp or less, about 20 bp or less, about 15 bp or less, about 10 bp or less, or about 5 bp or less in length. In some embodiments, the insertion is about 12 bp in length. Suitably, a variant spliceosomal intron may be obtained by modifying the wild-type spliceosomal intron to delete nucleotide sequences upstream of the branch point sequence. Sequences downstream of the 5’ splice donor site and upstream of the branch point sequence may be deleted without affecting the ability of the spliceosomal intron to increase expression of a protein-coding sequence. Moreover, the present inventors have surprisingly found that deletion of the 5’ splice donor site may not affect the ability of a spliceosomal intron to increase expression of a protein-coding sequence. In some embodiments, the 5’ splice donor site is deleted. Suitably, the deletion is about 80 bp or less, about 75 bp or less, about 70 bp or less, about 65 bp or less, about 60 bp or less, about 55 bp or less, about 50 bp or less, about 45 bp or less, about 40 bp or less, about 40 bp or less, about 35 bp or less, about 30 bp or less, or about 25 bp or less in length. In some embodiments, the deletion is about 22 bp in length and includes the 5’ splice donor site. Suitably, a variant spliceosomal intron may have a length of about 1000 bp or less, about 900 bp or less, about 800 bp or less, about 700 bp or less, about 600 bp or less, about 500 bp or less, about 400 bp or less, about 300 bp or less, about 200 bp or less, about 150 bp or less, about 140 bp or less, or about 130 bp or less. Suitably, a variant spliceosomal intron may have a length of about 40 bp or more, about 50 bp or more, about 60 bp or more, about 70 bp or more, about 80 bp or more, about 90 bp or more, about 100 bp or more, about 100 bp or more, about 105 bp or more, about 110 bp or more, about 115 bp or more, or about 120 bp or more. Suitably, a variant spliceosomal intron may have a length of from about 100 bp to about 1000 bp, from about 100 bp to about 900 bp, from about 100 bp to about 800 bp, from about 100 bp to about 700 bp, from about 100 bp to about 600 bp, from about 100 bp to about 500 bp, from about 100 bp to about 400 bp, from about 100 bp to about 300 bp, from about 100 bp to about 200 bp, or from about 100 bp to about 150 bp. Suitably, a variant spliceosomal intron may comprise or consist of the nucleotide sequence (N)xYTNAY(N)n1(Y)n2(N)n3YAGG, wherein x is from about 10 to about 1000 (e.g. from about 10 to about 100), n1 is from about 2 to about 22, n2 is from about 10 to about 20, and n1 + n2 + n3 is from about 15 to about 40, or a nucleotide sequence having five or fewer, four or fewer, three or fewer, two or fewer, or one nucleotide substitution. Rabbit beta globin introns The spliceosomal intron may be a rabbit beta globin intron or a variant thereof. The rabbit beta globin (RBG) gene may have GenBank accession number V00882. The RBG intron I may comprise or consist of the nucleotide sequence of SEQ ID NO: 2. The RBG intron II may comprise or consist of the nucleotide sequence of SEQ ID NO: 3. gttggtatcctttttacagcacaacttaatgagacagatagaaactggtcttgtagaaacag agtagtcgcctgcttttctgccaggtgctgacttctctcccctgggctgttttcattttctc agg Rabbit beta globin intron I (SEQ ID NO: 2) gtgagtttggggacccttgattgttctttctttttcgctattgtaaaattcatgttatatgg agggggcaaagttttcagggtgttgtttagaatgggaagatgtcccttgtatcaccatggac cctcatgataattttgtttctttcactttctactctgttgacaaccattgtctcctcttatt ttcttttcattttctgtaactttttcgttaaactttagcttgcatttgtaacgaatttttaa attcacttttgtttatttgtcagattgtaagtactttctctaatcacttttttttcaaggca atcagggtatattatattgtacttcagcacagttttagagaacaattgttataattaaatga taaggtagaatatttctgcatataaattctggctggcgtggaaatattcttattggtagaaa caactacatcctggtcatcatcctgcctttctctttatggttacaatgatatacactgtttg agatgaggataaaatactctgagtccaaaccgggcccctctgctaaccatgttcatgccttc ttctttttcctacagc Rabbit beta globin intron II (SEQ ID NO: 3) In some embodiments, the spliceosomal intron is a rabbit beta globin intron or a variant thereof having 70% or more, 75% or more, 80% or more, 81% or more, 82% or more, 83% or more, 84% or more, 85% or more, 86% or more, 87% or more, 88% or more, 89% or more, 90% or more, 91% or more, 92% or more, 93% or more, 94% or more, 95% or more, 96% or more, 97% or more, 98% or more, 99% or more, or 100% sequence identity thereto. In some embodiments, the spliceosomal intron is the rabbit beta globin intron I or a variant thereof having 70% or more, 75% or more, 80% or more, 81% or more, 82% or more, 83% or more, 84% or more, 85% or more, 86% or more, 87% or more, 88% or more, 89% or more, 90% or more, 91% or more, 92% or more, 93% or more, 94% or more, 95% or more, 96% or more, 97% or more, 98% or more, 99% or more, or 100% sequence identity thereto. In some embodiments, the spliceosomal intron is the rabbit beta globin intron I or a variant thereof having 80% or more, 81% or more, 82% or more, 83% or more, 84% or more, 85% or more, 86% or more, or 87% or more sequence identity thereto. In some embodiments, the variant has 87% or less sequence identity thereto. An example RBG intron I variant is provided below in SEQ ID NO: 4. Compared to the RBG intron I, the polypyrimidine tract sequence has been altered by substituting the native G and A residues in this region with T to increase the polypyrimidine tract consensus. gttggtatcctttttacagcacaacttaatgagacagatagaaactggtcttgtagaaacag agtagtcgcctgcttttctgccaggtgctgacttctctcccctgggcttttttctttttctc agg Example RBG intron I variant (SEQ ID NO: 4) In some embodiments, the spliceosomal intron does not comprise a HTLV-IR 5′ splice donor site. In some embodiments, the spliceosomal intron does not comprise the nucleotide sequence GTAAGT upstream of the branch point sequence. In some embodiments, the spliceosomal intron does not comprise a HTLV-IR 5′ intronic splice donor region. In some embodiments, the spliceosomal intron does not comprise a nucleotide sequence having 70% or more, 75% or more, 80% or more, 81% or more, 82% or more, 83% or more, 84% or more, 85% or more, 86% or more, 87% or more, 88% or more, 89% or more, 90% or more, 91% or more, 92% or more, 93% or more, 94% or more, 95% or more, 96% or more, 97% or more, 98% or more, 99% or more, or 100% sequence identity to SEQ ID NO: 5. In some embodiments, the spliceosomal intron does not comprise the nucleotide sequence of SEQ ID NO: 5. gtaagtttaaagctcaggtcgagaccgggcctttgtccggcgctcccttggagcctacctag actcagccggctctccacgctttgcctgaccctgcttgctcaactct HTLV-IR 5′ intronic splice donor region (SEQ ID NO: 5) Spliceosomal intron fragments The regulatory element may be a fragment of any naturally-occurring, chimeric, or variant spliceosomal intron, comprising or consisting of the following conserved elements from 5’ to 3’: a branch point sequence; a polypyrimidine tract; and a 3’ splice acceptor site. In preferred embodiments, the regulatory element does not comprise a 5’ splice donor site. In some embodiments, the regulatory element does not comprise the nucleotide sequence GTRAGT upstream of the branch point sequence. In some embodiments, the regulatory element does not comprise the nucleotide sequence GTTGGT upstream of the branch point sequence. In some embodiments, the regulatory element does not comprise a HTLV-IR 5′ splice donor site. In some embodiments, the regulatory element does not comprise the nucleotide sequence GTAAGT upstream of the branch point sequence. The regulatory element may comprise each of the branch point sequence, the polypyrimidine tract, and the 3’ splice acceptor site in consensus positions. Suitably, the polypyrimidine tract is from about 4 to about 24 bp downstream of the branch point. Suitably, the 3’ splice point is from about 21 to about 34 bp downstream of the branch point. The regulatory element may comprise a consensus branch point sequence, a consensus polypyrimidine tract, and / or a consensus 3’ splice acceptor site. In some embodiments, the regulatory element comprises at least a consensus branch point sequence and a consensus 3’ splice acceptor site. In some embodiments, the regulatory element comprises a consensus branch point sequence, a consensus polypyrimidine tract, and a consensus 3’ splice acceptor site. Suitably, the regulatory element has a length of about 150 bp or less, about 145 bp or less, about 140 bp or less, about 135 bp or less, about 130 bp or less, about 125 bp or less, or about 120 bp or less. Suitably, the regulatory element has a length of about 25 bp or more, about 30 bp or more, about 35 bp or more, about 40 bp or more, about 45 bp or more, about 50 bp or more, about 55 bp or more, about 60 bp or more, about 65 bp or more, about 70 bp or more, about 75 bp or more, about 80 bp or more, about 85 bp or more, about 90 bp or more, about 95 bp or more, about 100 bp or more, about 105 bp or more, about 110 bp or more, or about 115 bp or more. Suitably, the regulatory element has a length of from about 100 bp to about 135 bp, from about 105 bp to about 130 bp, from about 110 bp to about 125 bp, or from about 115 bp to about 120 bp. In some embodiments, the regulatory element has a length of about 117 bp. In some embodiments, the regulatory element has a length of 117 bp. Suitably, the regulatory element may comprise or consist of the nucleotide sequence (N)xYTNAY(N)n1(Y)n2(N)n3YAGG, wherein x is from about 10 to about 1000 (e.g. from about 10 to about 100), n1 is from about 2 to about 22, n2 is from about 10 to about 20, and n1 + n2 + n3 is from about 15 to about 40, or a nucleotide sequence having five or fewer, four or fewer, three or fewer, two or fewer, or one nucleotide substitution. Suitably, the regulatory element may comprise or consist of the nucleotide sequence (N)xYTNAY(N)n1(Y)n2(N)n3YAGG, wherein x is from about 10 to about 1000 (e.g. from about 10 to about 100), n1 is from about 2 to about 22, n2 is from about 10 to about 20, and n1 + n2 + n3 is from about 15 to about 40. Suitably, the regulatory element may comprise or consist of the nucleotide sequence YTNAY(N)n1(Y)n2(N)n3YAGG, wherein n1 is from about 2 to about 22, n2 is from about 10 to about 20, and n1 + n2 + n3 is from about 15 to about 40, or a nucleotide sequence having five or fewer, four or fewer, three or fewer, two or fewer, or one nucleotide substitution. Suitably, the regulatory element may comprise or consist of the nucleotide sequence YTNAY(N)n1(Y)n2(N)n3YAGG, wherein n1 is from about 2 to about 22, n2 is from about 10 to about 20, and n1 + n2 + n3 is from about 15 to about 40. Spliceosomal intron fragment variants The regulatory element may be derived from any naturally-occurring, chimeric, or variant spliceosomal intron. Suitably, a regulatory element may have 70% or more, 75% or more, 80% or more, 81% or more, 82% or more, 83% or more, 84% or more, 85% or more, 86% or more, 87% or more, 88% or more, 89% or more, 90% or more, 91% or more, 92% or more, 93% or more, 94% or more, 95% or more, 96% or more, 97% or more, 98% or more, 99% or more, or 100% sequence identity to a naturally-occurring, chimeric, or variant spliceosomal intron. A regulatory element may be obtained from a naturally-occurring, chimeric, or variant spliceosomal intron by substituting, inserting, and / or deleting 20 or fewer, 15 or fewer, 10 or fewer, 9 or fewer, 8 or fewer, 7 or fewer, 6 or fewer, 5 or fewer, 4 or fewer, 3 or fewer, 2 or fewer, or 1 nucleotide(s). A regulatory element may be obtained from a naturally-occurring, chimeric, or variant spliceosomal intron by substituting 10 or fewer, 9 or fewer, 8 or fewer, 7 or fewer, 6 or fewer, 5 or fewer, 4 or fewer, 3 or fewer, 2 or fewer, or 1 nucleotide(s). A regulatory element may be obtained from a naturally-occurring, chimeric, or variant spliceosomal intron by inserting 20 or fewer, 15 or fewer, 10 or fewer, 9 or fewer, 8 or fewer, 7 or fewer, 6 or fewer, 5 or fewer, 4 or fewer, 3 or fewer, 2 or fewer, or 1 nucleotide(s). A regulatory element may be obtained from a naturally-occurring, chimeric, or variant spliceosomal intron by deleting 20 or fewer, 15 or fewer, 10 or fewer, 9 or fewer, 8 or fewer, 7 or fewer, 6 or fewer, 5 or fewer, 4 or fewer, 3 or fewer, 2 or fewer, or 1 nucleotide(s). A regulatory element may be derived from a naturally-occurring, chimeric, or variant spliceosomal intron whilst retaining its ability to increase expression of a protein-coding sequence. Expression of a protein-coding sequence may be measured by any suitable method known in the art. For example by measuring the expression of a reporter transgene, e.g. Luciferase, placed downstream of the regulatory element, wherein expression of the reporter transgene correlates with the ability of the regulatory element to increase expression of a protein-coding sequence. Suitably, the regulatory element increases expression of a protein- coding sequence to at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or at least 100% of the level of the naturally-occurring, chimeric, or variant spliceosomal intron. Suitably, the naturally-occurring, chimeric, or variant spliceosomal intron may be modified to increase (or decrease) the consensus, to insert further nucleotide sequences, and / or to delete nucleotide sequences which are not required for the regulatory element to increase expression of a protein-coding sequence. Suitably, a regulatory element may be derived from a naturally-occurring, chimeric, or variant spliceosomal intron by modifying the sequence to increase the consensus. Suitably, the branch point sequence may be altered to consist of the consensus sequence YTNAY, the polypyrimidine tract may be altered to consist of (Y)n2, where n2 is from about 10 to about 20, and / or the 3’ splice acceptor site may be altered to consist of YAGG. In some embodiments, the branch point sequence is altered to consist of the nucleotide sequence TGCTGAC. In some embodiments, the polypyrimidine tract is altered to consist of the nucleotide sequence (Y)n2, where n2 is from about 10 to about 20. Alternatively (or additionally), a regulatory element may be derived from a naturally-occurring, chimeric, or variant spliceosomal intron by modifying the sequence to decrease the consensus, e.g. by making five or fewer, four or fewer, three or fewer, two or fewer, or one or fewer nucleotide substitution. In particular, the polypyrimidine tract may each be modified by making one or more nucleotide substitution. Such a modification may be made without affecting the ability of the regulatory element to increase expression of a protein-coding sequence. Suitably, a regulatory element may be derived from a naturally-occurring, chimeric, or variant spliceosomal intron by modifying the sequence to insert and / or delete nucleotide sequences such that the polypyrimidine tract and / or the 3’ splice acceptor site are in consensus positions. Suitably, one or more nucleotides sequences are inserted and / or deleted such that the polypyrimidine tract is about 4 to about 24 bp downstream of the branch point. Suitably, one or more nucleotides sequences are inserted and / or deleted such that the 3’ splice point is from about 21 to about 34 bp downstream of the branch point. Suitably, a regulatory element may be derived from a naturally-occurring, chimeric, or variant spliceosomal intron by modifying the sequence to insert nucleotide sequences. For example, one or more nucleotide sequences (e.g. one or more restriction site) may be introduced upstream of the branch point sequence without affecting the ability of the regulatory element to increase expression of a protein-coding sequence. Suitably, the insertion is about 100 bp or less, about 50 bp or less, about 45 bp or less, about 40 bp or less, about 40 bp or less, about 35 bp or less, about 30 bp or less, about 25 bp or less, about 20 bp or less, about 15 bp or less, about 10 bp or less, or about 5 bp or less in length. In some embodiments, the insertion is about 12 bp in length. Suitably, a regulatory element may be derived a naturally-occurring, chimeric, or variant spliceosomal intron by modifying the sequence to delete nucleotide sequences upstream of the branch point sequence. Sequences upstream of the branch point sequence may be deleted without affecting the ability of the regulatory element to increase expression of a protein-coding sequence. Suitably, the deletion is about 80 bp or less, about 75 bp or less, about 70 bp or less, about 65 bp or less, about 60 bp or less, about 55 bp or less, about 50 bp or less, about 45 bp or less, about 40 bp or less, about 40 bp or less, about 35 bp or less, about 30 bp or less, or about 25 bp or less in length. In some embodiments, the deletion is about 22 bp in length and includes the 5’ splice donor site. Example regulatory elements In some embodiments, the regulatory element is derived from a RBG intron or a variant thereof. In some embodiments, the regulatory element is derived from the RBG intron I. An example regulatory element derived from the RBG intron I is provided below in SEQ ID NO: 6. Compared to the RBG intron I, the polypyrimidine tract sequence has been altered by substituting the native G and A residues in this region with T to increase the polypyrimidine tract consensus; and 22 nucleotides at the 5’ end have been deleted, including the 5’ splice donor site. aacttaatgagacagatagaaactggtcttgtagaaacagagtagtcgcctgcttttctgcc aggtgctgacttctctcccctgggcttttttctttttctcagg Example regulatory element (SEQ ID NO: 6) In some embodiments, the regulatory element comprises or consists of a nucleotide sequence having 70% or more, 75% or more, 80% or more, 81% or more, 82% or more, 83% or more, 84% or more, 85% or more, 86% or more, 87% or more, 88% or more, 89% or more, 90% or more, 91% or more, 92% or more, 93% or more, 94% or more, 95% or more, 96% or more, 97% or more, 98% or more, 99% or more, or 100% sequence identity to SEQ ID NO: 6. In some embodiments, the regulatory element comprises or consists of a nucleotide sequence having 90% or more sequence identity to SEQ ID NO: 6. In some embodiments, the regulatory element comprises or consists of a nucleotide sequence having 95% or more sequence identity to SEQ ID NO: 6. In some embodiments, the regulatory element comprises or consists of a nucleotide sequence having 96% or more sequence identity to SEQ ID NO: 6. In some embodiments, the regulatory element comprises or consists of a nucleotide sequence having 97% or more sequence identity to SEQ ID NO: 6. In some embodiments, the regulatory element comprises or consists of a nucleotide sequence having 98% or more sequence identity to SEQ ID NO: 6. In some embodiments, the regulatory element comprises or consists of a nucleotide sequence having 99% or more sequence identity to SEQ ID NO: 6. In some embodiments, the regulatory element comprises or consists of the nucleotide sequence SEQ ID NO: 6, or a variant thereof having 5 or fewer, 4 or fewer, 3 or fewer, 2 or fewer, or 1 nucleotide substitution(s), deletion(s), and / or insertion(s). In some embodiments, the regulatory element comprises or consists of the nucleotide sequence SEQ ID NO: 6, or a variant thereof having 5 or fewer, 4 or fewer, 3 or fewer, 2 or fewer, or 1 nucleotide substitution(s). In some embodiments, the regulatory element comprises or consists of the nucleotide sequence SEQ ID NO: 6. Another example regulatory element derived from the RBG intron I is provided below in SEQ ID NO: 7. Compared to SEQ ID NO: 6, 12 nucleotides have been inserted at the 5’ end (including a restriction site but not including a 5’ splice donor site). agttctctcgttaacttaatgagacagatagaaactggtcttgtagaaacagagtagtcgcc tgcttttctgccaggtgctgacttctctcccctgggcttttttctttttctcagg Example regulatory element (SEQ ID NO: 7) In some embodiments, the regulatory element comprises or consists of a nucleotide sequence having 70% or more, 75% or more, 80% or more, 81% or more, 82% or more, 83% or more, 84% or more, 85% or more, 86% or more, 87% or more, 88% or more, 89% or more, 90% or more, 91% or more, 92% or more, 93% or more, 94% or more, 95% or more, 96% or more, 97% or more, 98% or more, 99% or more, or 100% sequence identity to SEQ ID NO: 7. In some embodiments, the regulatory element comprises or consists of a nucleotide sequence having 90% or more sequence identity to SEQ ID NO: 7. In some embodiments, the regulatory element comprises or consists of a nucleotide sequence having 95% or more sequence identity to SEQ ID NO: 7. In some embodiments, the regulatory element comprises or consists of a nucleotide sequence having 96% or more sequence identity to SEQ ID NO: 7. In some embodiments, the regulatory element comprises or consists of a nucleotide sequence having 97% or more sequence identity to SEQ ID NO: 7. In some embodiments, the regulatory element comprises or consists of a nucleotide sequence having 98% or more sequence identity to SEQ ID NO: 7. In some embodiments, the regulatory element comprises or consists of a nucleotide sequence having 99% or more sequence identity to SEQ ID NO: 7. In some embodiments, the regulatory element comprises or consists of the nucleotide sequence SEQ ID NO: 7, or a variant thereof having 5 or fewer, 4 or fewer, 3 or fewer, 2 or fewer, or 1 nucleotide substitution(s), deletion(s), and / or insertion(s). In some embodiments, the regulatory element comprises or consists of the nucleotide sequence SEQ ID NO: 7, or a variant thereof having 5 or fewer, 4 or fewer, 3 or fewer, 2 or fewer, or 1 nucleotide substitution(s). In some embodiments, the regulatory element comprises or consists of the nucleotide sequence SEQ ID NO: 7. In some embodiments, the regulatory element consists of the nucleotide sequence SEQ ID NO: 7, or a variant thereof having 5 or fewer, 4 or fewer, 3 or fewer, 2 or fewer, or 1 nucleotide substitution(s), deletion(s), and / or insertion(s). In some embodiments, the regulatory element consists of the nucleotide sequence SEQ ID NO: 7, or a variant thereof having 5 or fewer, 4 or fewer, 3 or fewer, 2 or fewer, or 1 nucleotide substitution(s). In some embodiments, the regulatory element consists of the nucleotide sequence SEQ ID NO: 7. In some embodiments, the regulatory element does not comprise a HTLV-IR 5′ intronic splice donor region. In some embodiments, the regulatory element does not comprise a nucleotide sequence having 70% or more, 75% or more, 80% or more, 81% or more, 82% or more, 83% or more, 84% or more, 85% or more, 86% or more, 87% or more, 88% or more, 89% or more, 90% or more, 91% or more, 92% or more, 93% or more, 94% or more, 95% or more, 96% or more, 97% or more, 98% or more, 99% or more, or 100% sequence identity to SEQ ID NO: 5. In some embodiments, the regulatory element does not comprise the nucleotide sequence of SEQ ID NO: 5. Example NPHS1 promoter-regulatory element In some embodiments, the polynucleotide comprises a NPHS1 promoter comprising or consisting of a nucleotide sequence having 70% or more, 75% or more, 80% or more, 85% or more, 90% or more, 91% or more, 92% or more, 93% or more, 94% or more, 95% or more, 96% or more, 97% or more, 98% or more, 99% or more, or 100% sequence identity to SEQ ID NO: 1 and a regulatory element comprising or consisting of a nucleotide sequence having 70% or more, 75% or more, 80% or more, 85% or more, 90% or more, 91% or more, 92% or more, 93% or more, 94% or more, 95% or more, 96% or more, 97% or more, 98% or more, 99% or more, or 100% sequence identity to SEQ ID NO: 7. In some embodiments, the polynucleotide comprises a NPHS1 promoter comprising or consisting of a nucleotide sequence having 70% or more sequence identity to SEQ ID NO: 1 and a regulatory element comprising or consisting of a nucleotide sequence having 70% or more sequence identity to SEQ ID NO: 7. In some embodiments, the polynucleotide comprises a NPHS1 promoter comprising or consisting of a nucleotide sequence having 75% or more sequence identity to SEQ ID NO: 1 and a regulatory element comprising or consisting of a nucleotide sequence having 75% or more sequence identity to SEQ ID NO: 7. In some embodiments, the polynucleotide comprises a NPHS1 promoter comprising or consisting of a nucleotide sequence having 80% or more sequence identity to SEQ ID NO: 1 and a regulatory element comprising or consisting of a nucleotide sequence having 80% or more sequence identity to SEQ ID NO: 7. In some embodiments, the polynucleotide comprises a NPHS1 promoter comprising or consisting of a nucleotide sequence having 85% or more sequence identity to SEQ ID NO: 1 and a regulatory element comprising or consisting of a nucleotide sequence having 85% or more sequence identity to SEQ ID NO: 7. In some embodiments, the polynucleotide comprises a NPHS1 promoter comprising or consisting of a nucleotide sequence having 90% or more sequence identity to SEQ ID NO: 1 and a regulatory element comprising or consisting of a nucleotide sequence having 90% or more sequence identity to SEQ ID NO: 7. In some embodiments, the polynucleotide comprises a NPHS1 promoter comprising or consisting of a nucleotide sequence having 95% or more sequence identity to SEQ ID NO: 1 and a regulatory element comprising or consisting of a nucleotide sequence having 95% or more sequence identity to SEQ ID NO: 7. In some embodiments, the polynucleotide comprises a NPHS1 promoter comprising or consisting of a nucleotide sequence having 96% or more sequence identity to SEQ ID NO: 1 and a regulatory element comprising or consisting of a nucleotide sequence having 96% or more sequence identity to SEQ ID NO: 7. In some embodiments, the polynucleotide comprises a NPHS1 promoter comprising or consisting of a nucleotide sequence having 97% or more sequence identity to SEQ ID NO: 1 and a regulatory element comprising or consisting of a nucleotide sequence having 97% or more sequence identity to SEQ ID NO: 7. In some embodiments, the polynucleotide comprises a NPHS1 promoter comprising or consisting of a nucleotide sequence having 98% or more sequence identity to SEQ ID NO: 1 and a regulatory element comprising or consisting of a nucleotide sequence having 98% or more sequence identity to SEQ ID NO: 7. In some embodiments, the polynucleotide comprises a NPHS1 promoter comprising or consisting of a nucleotide sequence having 99% or more sequence identity to SEQ ID NO: 1 and a regulatory element comprising or consisting of a nucleotide sequence having 99% or more sequence identity to SEQ ID NO: 7. In some embodiments, the polynucleotide comprises a NPHS1 promoter comprising or consisting of the nucleotide sequence of SEQ ID NO: 1 and a regulatory element comprising or consisting of the nucleotide sequence of SEQ ID NO: 7. In some embodiments, the polynucleotide comprises a NPHS1 promoter consisting of the nucleotide sequence of SEQ ID NO: 1 and a regulatory element consisting of the nucleotide sequence of SEQ ID NO: 7. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 70% identical to SEQ ID NO: 51. Suitably, the polynucleotide comprises a nucleotide sequence which is at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 51. In some embodiments, the polynucleotide comprises the nucleotide sequence SEQ ID NO: 51. cacctgaggtcaggagttcgagaccagcgtggccaacatgatgaaaccccgtctctagtaaa aatacaaaaattagccaggcatggtgctatatacctgtagcaccagctacttgggagacaga ggtgggagaattacttgaacctgggaggttcaagccatgggaggtggaagttgcagtgagcc gagatgccactgcactccagcctgagcaacagagcaagactatctcaagaaaagaaagaaag aaagaaagagacttgccaaggtcatgtatcagggcaaggaagagctgggggcccagctggct gctcccctgctgagctgggagaccaccttgatctgacttctcccatcttcccagcctaagcc aggccctggggtcacggaggctggggaggcaccgaggaacgcgcctggcatgtgctgacagg ggattttatgctccagctgggccagctgggaggagcctgctgggcagaggccagagctgggg gctctggaaggtacctgggggaggttgcactgtgagaatgagctcaagctgggtcagagagc agggctgactctgccagtgcctgcatcagcctcatcgctctcctaggctcctggcctgctgg actctgggctgcaggtccttcttgaaaggctgtgagtagtgagacaaggagcaggagtgagg ggtggcaggagagaagatagagattgagagagagagagagagagagacagagagagaggaag agacagagacaaaaggagagagaacggcttagacaaggagagaaagatggaaagataaagag actgggcgcagtggctcacgcctgtaatcccaacacttggggaggccaaggtgggaggatgg cttgaaggaaagagtctgagatcaacctggccaacatagtgagaccccgtctctaaaaaaaa aagaaaaaaaaaagaaaaaagaaaaaaaagtttttttaaagagacagagaaagagactcaga gattgagactgagagcaagacagagagagatactcacagggaagaggggaagaggaaaacga gaaagggaggagagtaacggaaagagataaaaaagaaaagcaggtggcagagacacacagag agggacccagagaaagccagacagacgcaggtggctggcagcgggcgctgtgggggtcacag tagggggacctgtg(n)agttctctcgttaacttaatgagacagatagaaactggtcttgta gaaacagagtagtcgcctgcttttctgccaggtgctgacttctctcccctgggcttttttct ttttctcagg wherein x is from 0 to 100 Example NPHS1 promoter-regulatory element (SEQ ID NO: 51) In some embodiments, x is from 1 to 100, from 2 to 100, from 3 to 100, from 4 to 100, from 5 to 100, from 6 to 100, from 7 to 100, from 8 to 100, from 9 to 100, or from 10 to 100. In some embodiments, x is from 1 to 50, from 2 to 50, from 3 to 50, from 4 to 50, from 5 to 50, from 6 to 50, from 7 to 50, from 8 to 50, from 9 to 50, or from 10 to 50. In some embodiments, (n)xis selected from any of SEQ ID NOs: 12-33. In some embodiments, (n)xis selected from any of SEQ ID NOs: 22-33. In some embodiments, (n)xis selected from any of SEQ ID NOs: 27-31. Protein-coding sequences The polynucleotide of the present invention comprises a protein-coding sequence encoding podocin. Podocin polypeptides Podocin is a 42kDa hairpin like membrane-associated podocyte-specific protein that is a key component of the protein complex at the slit diaphragm; the cell-cell junction between adjacent podocyte foot processes. It localises to lipid rafts and interacts with other important slit diaphragm proteins like nephrin, CD2AP and TRPC6. It is essential in the maintenance of the slit diaphragm, and consequently the integrity of the glomerular filtration barrier. Podocin is encoded by the NPHS2 gene. The NPHS2 gene is conserved in humans, chimpanzees, Rhesus monkeys, dogs, cows, mice, and rats. In preferred embodiments, the podocin is a human podocin. A human podocin may consist of a polypeptide sequence of UniProtKB accession Q9NP85. A mouse podocin may consist of a polypeptide sequence of UniProtKB accession Q91X05, which has 86.0% sequence identity to Q9NP85. A rat podocin may consist of a polypeptide sequence of UniProtKB accession Q8K4G9, which has 85.1% sequence identity to Q9NP85. In some embodiments, the podocin comprises or consists of an amino acid sequence which is at least 70% identical to SEQ ID NO: 8. Suitably, the podocin comprises or consists of an amino acid sequence which is at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 8. In some embodiments, the podocin comprises or consists of the amino acid sequence of SEQ ID NO: 8. In some embodiments, the podocin consists of an amino acid sequence which is at least 70% identical to SEQ ID NO: 8. Suitably, the podocin consists of an amino acid sequence which is at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 8. In some embodiments, the podocin consists of the amino acid sequence of SEQ ID NO: 8. MERRARSSSRESRGRGGRTPHKENKRAKAERSGGGRGRQEAGPEPSGSGRAGTPGEPRAPAA TVVDVDEVRGSGEEGTEVVALLESERPEEGTKSSGLGACEWLLVLISLLFIIMTFPFSIWFC VKVVQEYERVIIFRLGHLLPGRAKGPGLFFFLPCLDTYHKVDLRLQTLEIPFHEIVTKDMFI MEIDAICYYRMENASLLLSSLAHVSKAVQFLVQTTMKRLLAHRSLTEILLERKSIAQDAKVA LDSVTCIWGIKVERIEIKDVRLPAGLQHSLAVEAEAQRQAKVRMIAAEAEKAASESLRMAAE ILSGTPAAVQLRYLHTLQSLSTEKPSTVVLPLPFDLLNCLSSPSNRTQGSLPFPSPSKPVEP LNPKKKDSPML Example human podocin amino acid sequence (SEQ ID NO: 8) In preferred embodiments, the protein-coding sequence encodes a full-length wild-type podocin. In more preferred embodiments, the protein-coding sequence encodes a full-length wild-type human podocin. Although it is preferred that the protein-coding sequence encodes a full-length wild-type podocin, the protein-coding sequence may alternatively encode a fragment and / or variant of podocin that retains podocin activity and / or function. For example, a fragment and / or variant of podocin that regulates glomerular permeability. Suitably, a fragment and / or variant of podocin may have the same or similar activity and / or function to podocin, e.g. may have at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or at least 100% of the activity and / or function of podocin. A person skilled in the art would be able to generate fragments and / or variants of podocin using conservative substitutions, based on the known structural and functional features of podocin (see e.g. Tabassum, A., et al., 2014. Interdisciplinary Sciences: Computational Life Sciences, 6(1), pp.32-39), and / or based on known variants (see e.g. NCBI Gene ID: 7827 and NCBI HomoloGene: 22826). Suitably, a fragment and / or variant of podocin comprises a transmembrane domain, with two cytoplasmic domains at the N- and C-terminus. Podocin polynucleotides For a protein-coding polynucleotide, it will be understood by a skilled person that numerous different polynucleotides can encode the same polypeptide as a result of the degeneracy of the genetic code. In addition, it is to be understood that skilled persons may, using routine techniques, make nucleotide substitutions that do not affect the polypeptide sequence encoded by the polynucleotides of the invention to reflect the codon usage of any particular host organism in which the polypeptides of the invention are to be expressed. The protein-coding sequence may be codon-optimised. Different cells differ in their usage of particular codons. This codon bias corresponds to a bias in the relative abundance of particular tRNAs in the cell type. By altering the codons in the sequence so that they are tailored to match with the relative abundance of corresponding tRNAs, it is possible to increase expression. By the same token, it is possible to decrease expression by deliberately choosing codons for which the corresponding tRNAs are known to be rare in the particular cell type. Thus, an additional degree of translational control is available. Codon usage tables are known in the art for mammalian cells (e.g. humans), as well as for a variety of other organisms. The protein-coding sequences disclosed herein may comprise or lack stop codons at their 3’ end. The present disclosure encompasses the SEQ ID NOs disclosed herein with the stop codons present or absent. In some embodiments, the protein-coding sequence encoding podocin comprises or consists of a nucleotide sequence which is at least 70% identical to SEQ ID NO: 9. Suitably, the protein- coding sequence encoding podocin comprises or consists of a nucleotide sequence which is at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 9. In some embodiments, the protein-coding sequence encoding podocin comprises or consists of the nucleotide sequence of SEQ ID NO: 9. In some embodiments, the protein-coding sequence encoding podocin consists of a nucleotide sequence which is at least 70% identical to SEQ ID NO: 9. Suitably, the protein- coding sequence encoding podocin consists of a nucleotide sequence which is at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 9. In preferred embodiments, the protein-coding sequence encoding podocin consists of the nucleotide sequence of SEQ ID NO: 9. atggagaggagggcgcggagctcctccagggagtcccgcgggcgaggcggcaggactccgca caaggagaacaagagggcaaaggccgagaggagcggcgggggccgcgggcgccaggaggctg ggcccgagccgtcgggctccggacgggcggggaccccgggggagccccgagcgcccgccgcc acggtggtggacgtggatgaggtccgaggctccggcgaggagggcaccgaggtggtggcgct gttggagagcgagcggcccgaggaaggtaccaaatcctccggcttaggggcctgtgagtggc ttcttgtcctcatttccctgctcttcatcatcatgaccttccctttttccatctggttctgc gtaaaggttgtacaagagtatgaaagagtaattatattccgactgggacatctgcttcctgg aagagccaaaggccctggtcttttcttttttttgccctgcctggatacctaccacaaggttg accttcgtctccaaactctggagataccttttcatgagatcgtgaccaaagacatgtttata atggagatagatgccatttgctactaccgaatggaaaatgcctctcttctcctaagcagtct tgctcatgtatctaaagctgtgcaattccttgtgcaaaccactatgaagcgtctcctagcac atcgatccctcactgaaattcttctagagaggaagagcatcgcccaagatgcaaaggttgcc ttggattcagtgacctgtatttggggaatcaaagtggagagaatagaaattaaagatgtgag gttgccagctgggcttcagcactcactggctgtggaggctgaagcgcaaagacaagccaaag tgcggatgattgctgcagaagcggaaaaggctgcttctgagtccctgaggatggcagctgag attctgtcaggcacccctgctgctgttcagcttcgatacctccacacccttcagtctctgtc cacagagaagccttccactgtggttttacctttgccatttgacctactgaattgcctgtctt ctcccagcaacagaactcagggaagcctccccttcccaagtccttccaaacctgttgagcca ctaaatcctaaaaagaaagactctcccatgtta Example podocin nucleotide sequence (SEQ ID NO: 9) Woodchuck Hepatitis Virus Post-transcriptional Regulatory Element (WPRE) In some embodiments, the polynucleotide of the present invention further comprises a Woodchuck Hepatitis Virus Post-transcriptional Regulatory Element (WPRE). Suitably, the WPRE may be operably linked to the protein-coding sequence. In some embodiments, the polynucleotide comprises from 5’ to 3’: a 5’ ITR; a kidney-specific promoter; a regulatory element comprising a spliceosomal intron or a fragment thereof comprising a branch point sequence, a polypyrimidine tract, and a 3’ splice acceptor site; a protein-coding sequence encoding podocin; a WPRE; and a 3’ ITR. The WPRE sequence may have mutations within the X-antigen promoter and / or the initiation codon of the X-antigen. This may prevent the production of a functional X-antigen. Suitably, the WPRE may comprise or consist of the nucleotide sequence shown as SEQ ID NO: 10, or a variant which is at least 70% identical to SEQ ID NO: 10. Suitably, the variant may be at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 96%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 10. In preferred embodiments, the WPRE consists of the nucleotide sequence shown as SEQ ID NO: 10. aatcaacctctggattacaaaatttgtgaaagattgactggtattcttaactatgttgctcc ttttacgctatgtggatacgctgctttaatgcctttgtatcatgctattgcttcccgtatgg ctttcattttctcctccttgtataaatcctggttgctgtctctttatgaggagttgtggccc gttgtcaggcaacgtggcgtggtgtgcactgtgtttgctgacgcaacccccactggttgggg cattgccaccacctgtcagctcctttccgggactttcgctttccccctccctattgccacgg cggaactcatcgccgcctgccttgcccgctgctggacaggggctcggctgttgggcactgac aattccgtggtgttgtcggggaaatcatcgtcctttccttggctgctcgcctgtgttgccac ctggattctgcgcgggacgtccttctgctacgtcccttcggccctcaatccagcggaccttc cttcccgcggcctgctgccggctctgcggcctcttccgcgtcttcgccttcgccctcagacg agtcggatctccctttgggccgcctccccgc Example WPRE (SEQ ID NO: 10) Polyadenylation sequence In some embodiments, the polynucleotide of the present invention further comprises a polyadenylation sequence. Suitably, the polyadenylation sequence may be operably linked to the protein-coding sequence. In some embodiments, the polynucleotide comprises from 5’ to 3’: a 5’ ITR; a kidney-specific promoter; a regulatory element comprising a spliceosomal intron or a fragment thereof comprising a branch point sequence, a polypyrimidine tract, and a 3’ splice acceptor site; a protein-coding sequence encoding podocin; a polyadenylation sequence; and a 3’ ITR. In some embodiments, the polynucleotide comprises from 5’ to 3’: a 5’ ITR; a kidney-specific promoter; a regulatory element comprising a spliceosomal intron or a fragment thereof comprising a branch point sequence, a polypyrimidine tract, and a 3’ splice acceptor site; a protein-coding sequence encoding podocin; a WPRE; a polyadenylation sequence; and a 3’ ITR. Suitable polyadenylation sequences include the early SV40 polyadenylation sequence (SV40pA), a bovine growth hormone polyadenylation sequence (bGH), or a soluble neuropilin- 1 polyadenylation sequence. Preferably, the polyadenylation sequence is a bGH polyadenylation sequence. Suitably, the polyadenylation sequence may comprise or consist of the nucleotide sequence shown as SEQ ID NO: 11, or a variant which is at least 70% identical to SEQ ID NO: 11. Suitably, the variant may be at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 96%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 11. In preferred embodiments, the polyadenylation sequence consists of the nucleotide sequence shown as SEQ ID NO: 11. ctgtgccttctagttgccagccatctgttgtttgcccctcccccgtgccttccttgaccctg gaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgag taggtgtcattctattctggggggtggggtggggcaggacagcaagggggaggattgggaag acaatagcaggcatgctggggatgcggtgggctctatgg Example bGH poly(A) sequence (SEQ ID NO: 11) Kozak sequences In some embodiments, the polynucleotide of the present invention further comprises a Kozak sequence. Suitably, the Kozak sequence may be operably linked to the protein-coding sequence. A Kozak sequence may be inserted around the start codon of the protein-coding sequence to improve the initiation of translation. In some embodiments, the polynucleotide comprises from 5’ to 3’: a 5’ ITR; a kidney-specific promoter; a regulatory element comprising a spliceosomal intron or a fragment thereof comprising a branch point sequence, a polypyrimidine tract, and a 3’ splice acceptor site; a Kozak sequence; a protein-coding sequence encoding podocin; optionally, a WPRE; optionally, a polyadenylation sequence; and a 3’ ITR. Suitable Kozak sequences will be well known to those of skill in the art (see e.g. Kozak, M., 2002. Gene, 299(1-2), pp.1-34). A consensus Kozak sequence in vertebrates may have the sequence of SEQ ID NO: 48 or SEQ ID NO: 49. Suitably, the Kozak sequence may comprise or consist of the nucleotide sequence of SEQ ID NO: 48 or 49, or variants thereof which have five or fewer deletions, substitutions or insertions. Suitably, the variants may have four or fewer, three or fewer, two or fewer, or one deletion(s), substitution(s) or insertion(s). Suitably, the variants may have three or fewer, two or fewer, or one deletion(s) and / or three or fewer, two or fewer, or one substitution(s). Suitably, the variants may have three or fewer, two or fewer, or one deletion(s) and / or three or fewer, two or fewer, or one substitution(s). Suitably, the variants may have one deletion and / or one substitution. Suitably, the variants may have one deletion and one substitution. gccrccatgg Example consensus Kozak sequence 1 (SEQ ID NO: 48) gccgccrccatgg Example consensus Kozak sequence 2 (SEQ ID NO: 49) Suitably, the Kozak sequence may comprise or consist of the nucleotide sequence shown as SEQ ID NO: 50, or a variant which is at least 60% identical to SEQ ID NO: 50. Suitably, the variant may be at least 70%, at least 80%, or at least 90% identical to SEQ ID NO: 50. In some embodiments, the Kozak sequence comprises or consists of the nucleotide sequence shown as SEQ ID NO: 50. In some embodiments, the Kozak sequence consists of the nucleotide sequence shown as SEQ ID NO: 50. gccaccatgg Example Kozak sequence (SEQ ID NO: 50) Inverted terminal repeats (ITRs) The polynucleotide further comprises a 5’ ITR and a 3’ ITR. The ITR sequences may be from any naturally derived serotype, isolate or clade of AAV or a variant thereof. The polynucleotide may comprise at least one, such as two, AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAV10, or AAV11 ITRs, or variants thereof. In some embodiments, the polynucleotide comprises a 5’ AAV2 ITR and / or a 3’ AAV2 ITR. In some embodiments, the polynucleotide comprises a 5’ AAV2 ITR and a 3’ AAV2 ITR. ITR sequences for use in the invention may be derived from the following accession numbers for AAV whole genome sequences: Adeno-associated virus 1 NC_002077; Adeno-associated virus 2 NC_001401; Adeno-associated virus 3 NC_001729; Adeno-associated virus 4 NC_001829; Adeno-associated virus 5 NC_006152; Adeno-associated virus 6 AF028704; Adeno-associated virus 7 NC_006260; and Adeno-associated virus 8 NC_006261. Other suitable ITRs are described in Wilmott, P., et al., 2019. Human gene therapy methods, 30(6), pp.206-213. One or more of the ITRs may be derived from AAV genomes having different serotypes, or may be a chimeric or mutant ITR. A preferred mutant ITR is one having a deletion of a trs (terminal resolution site). This deletion allows for continued replication of the genome to generate a single-stranded genome which contains both coding and complementary sequences, i.e. a self-complementary AAV genome. This allows for bypass of DNA replication in the target cell, and so enables accelerated transgene expression. In some embodiments, the polynucleotide of the invention comprises a 5’ ITR comprising or consisting of a nucleotide sequence which is at least 70% identical to SEQ ID NO: 52. Suitably, the 5’ ITR comprises or consists of a nucleotide sequence which is at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identical to SEQ ID NO: 52. In some embodiments, the 5’ ITR comprises or consists of the nucleotide sequence of SEQ ID NO: 52. cctgcaggcagctgcgcgctcgctcgctcactgaggccgcccgggcaaagcccgggcgtcgg gcgacctttggtcgcccggcctcagtgagcgagcgagcgcgcagagagggagtggccaactc catcactaggggttcct Example 5’ ITR (SEQ ID NO: 52) In some embodiments, the polynucleotide of the invention comprises a 3’ ITR comprising or consisting of a nucleotide sequence which is at least 70% identical to SEQ ID NO: 53. Suitably, the 3’ ITR comprises or consists of a nucleotide sequence which is at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identical to SEQ ID NO: 53. In some embodiments, the 3’ ITR comprises or consists of the nucleotide sequence of SEQ ID NO: 53. aggaacccctagtgatggagttggccactccctctctgcgcgctcgctcgctcactgaggcc gggcgaccaaaggtcgcccgacgcccgggctttgcccgggcggcctcagtgagcgagcgagc gcgcagctgcctgcagg Example 3’ ITR (SEQ ID NO: 53) In some embodiments, the polynucleotide of the invention comprises a 5’ ITR comprising or consisting of a nucleotide sequence which is at least 70% identical to SEQ ID NO: 52 and a 3’ ITR comprising or consisting of a nucleotide sequence which is at least 70% identical to SEQ ID NO: 53. In some embodiments, the polynucleotide of the invention comprises a 5’ ITR comprising or consisting of the nucleotide sequence of SEQ ID NO: 52 and a 3’ ITR comprising or consisting of the nucleotide sequence of SEQ ID NO: 53. Example polynucleotides In some embodiments, the polynucleotide comprises: a 5’ ITR; a kidney-specific promoter consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 1; a regulatory element consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 7; a podocin coding sequence consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 9; optionally, a Woodchuck Hepatitis Virus Post-transcriptional Regulatory Element (WPRE) consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 10; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 11; and a 3’ ITR. In some embodiments, the polynucleotide comprises: a 5’ ITR; a kidney-specific promoter consisting of a nucleotide sequence having at least 85% sequence identity to SEQ ID NO: 1; a regulatory element consisting of a nucleotide sequence having at least 85% sequence identity to SEQ ID NO: 7; a podocin coding sequence consisting of a nucleotide sequence having at least 85% sequence identity to SEQ ID NO: 9; optionally, a Woodchuck Hepatitis Virus Post-transcriptional Regulatory Element (WPRE) consisting of a nucleotide sequence having at least 85% sequence identity to SEQ ID NO: 10; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 85% sequence identity to SEQ ID NO: 11; and a 3’ ITR. In some embodiments, the polynucleotide comprises: a 5’ ITR; a kidney-specific promoter consisting of a nucleotide sequence having at least 90% sequence identity to SEQ ID NO: 1; a regulatory element consisting of a nucleotide sequence having at least 90% sequence identity to SEQ ID NO: 7; a podocin coding sequence consisting of a nucleotide sequence having at least 90% sequence identity to SEQ ID NO: 9; optionally, a Woodchuck Hepatitis Virus Post-transcriptional Regulatory Element (WPRE) consisting of a nucleotide sequence having at least 90% sequence identity to SEQ ID NO: 10; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 90% sequence identity to SEQ ID NO: 11; and a 3’ ITR. In some embodiments, the polynucleotide comprises: a 5’ ITR; a kidney-specific promoter consisting of a nucleotide sequence having at least 95% sequence identity to SEQ ID NO: 1; a regulatory element consisting of a nucleotide sequence having at least 95% sequence identity to SEQ ID NO: 7; a podocin coding sequence consisting of a nucleotide sequence having at least 95% sequence identity to SEQ ID NO: 9; optionally, a Woodchuck Hepatitis Virus Post-transcriptional Regulatory Element (WPRE) consisting of a nucleotide sequence having at least 95% sequence identity to SEQ ID NO: 10; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 95% sequence identity to SEQ ID NO: 11; and a 3’ ITR. In some embodiments, the polynucleotide comprises: a 5’ ITR; a kidney-specific promoter consisting of a nucleotide sequence having at least 96% sequence identity to SEQ ID NO: 1; a regulatory element consisting of a nucleotide sequence having at least 96% sequence identity to SEQ ID NO: 7; a podocin coding sequence consisting of a nucleotide sequence having at least 96% sequence identity to SEQ ID NO: 9; optionally, a Woodchuck Hepatitis Virus Post-transcriptional Regulatory Element (WPRE) consisting of a nucleotide sequence having at least 96% sequence identity to SEQ ID NO: 10; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 96% sequence identity to SEQ ID NO: 11; and a 3’ ITR. In some embodiments, the polynucleotide comprises: a 5’ ITR; a kidney-specific promoter consisting of a nucleotide sequence having at least 97% sequence identity to SEQ ID NO: 1; a regulatory element consisting of a nucleotide sequence having at least 97% sequence identity to SEQ ID NO: 7; a podocin coding sequence consisting of a nucleotide sequence having at least 97% sequence identity to SEQ ID NO: 9; optionally, a Woodchuck Hepatitis Virus Post-transcriptional Regulatory Element (WPRE) consisting of a nucleotide sequence having at least 97% sequence identity to SEQ ID NO: 10; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 97% sequence identity to SEQ ID NO: 11; and a 3’ ITR. In some embodiments, the polynucleotide comprises: a 5’ ITR; a kidney-specific promoter consisting of a nucleotide sequence having at least 98% sequence identity to SEQ ID NO: 1; a regulatory element consisting of a nucleotide sequence having at least 98% sequence identity to SEQ ID NO: 7; a podocin coding sequence consisting of a nucleotide sequence having at least 98% sequence identity to SEQ ID NO: 9; optionally, a Woodchuck Hepatitis Virus Post-transcriptional Regulatory Element (WPRE) consisting of a nucleotide sequence having at least 98% sequence identity to SEQ ID NO: 10; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 98% sequence identity to SEQ ID NO: 11; and a 3’ ITR. In some embodiments, the polynucleotide comprises: a 5’ ITR; a kidney-specific promoter consisting of a nucleotide sequence having at least 99% sequence identity to SEQ ID NO: 1; a regulatory element consisting of a nucleotide sequence having at least 99% sequence identity to SEQ ID NO: 7; a podocin coding sequence consisting of a nucleotide sequence having at least 99% sequence identity to SEQ ID NO: 9; optionally, a Woodchuck Hepatitis Virus Post-transcriptional Regulatory Element (WPRE) consisting of a nucleotide sequence having at least 99% sequence identity to SEQ ID NO: 10; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 99% sequence identity to SEQ ID NO: 11; and a 3’ ITR. In some embodiments, the polynucleotide comprises: a 5’ ITR; a kidney-specific promoter consisting of a nucleotide sequence having 100% sequence identity to SEQ ID NO: 1; a regulatory element consisting of a nucleotide sequence having 100% sequence identity to SEQ ID NO: 7; a podocin coding sequence consisting of a nucleotide sequence having 100% sequence identity to SEQ ID NO: 9; optionally, a Woodchuck Hepatitis Virus Post- transcriptional Regulatory Element (WPRE) consisting of a nucleotide sequence having 100% sequence identity to SEQ ID NO: 10; optionally, a polyadenylation sequence consisting of a nucleotide sequence having 100% sequence identity to SEQ ID NO: 11; and a 3’ ITR. In some embodiments, the polynucleotide comprises: a 5’ ITR; a kidney-specific promoter consisting of the nucleotide sequence of SEQ ID NO: 1; a regulatory element consisting of the nucleotide sequence of SEQ ID NO: 7; a podocin coding sequence consisting of the nucleotide sequence of SEQ ID NO: 9; optionally, a Woodchuck Hepatitis Virus Post-transcriptional Regulatory Element (WPRE) consisting of the nucleotide sequence of SEQ ID NO: 10; optionally, a polyadenylation sequence consisting of the nucleotide sequence of SEQ ID NO: 11; and a 3’ ITR. In some embodiments, the polynucleotide comprises from 5’ to 3’: a 5’ ITR; a kidney-specific promoter consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 1; a regulatory element consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 7; a podocin coding sequence consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 9; optionally, a Woodchuck Hepatitis Virus Post-transcriptional Regulatory Element (WPRE) consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 10; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 11; and a 3’ ITR. In some embodiments, the polynucleotide comprises from 5’ to 3’: a 5’ ITR; a kidney-specific promoter consisting of a nucleotide sequence having at least 85% sequence identity to SEQ ID NO: 1; a regulatory element consisting of a nucleotide sequence having at least 85% sequence identity to SEQ ID NO: 7; a podocin coding sequence consisting of a nucleotide sequence having at least 85% sequence identity to SEQ ID NO: 9; optionally, a Woodchuck Hepatitis Virus Post-transcriptional Regulatory Element (WPRE) consisting of a nucleotide sequence having at least 85% sequence identity to SEQ ID NO: 10; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 85% sequence identity to SEQ ID NO: 11; and a 3’ ITR. In some embodiments, the polynucleotide comprises from 5’ to 3’: a 5’ ITR; a kidney-specific promoter consisting of a nucleotide sequence having at least 90% sequence identity to SEQ ID NO: 1; a regulatory element consisting of a nucleotide sequence having at least 90% sequence identity to SEQ ID NO: 7; a podocin coding sequence consisting of a nucleotide sequence having at least 90% sequence identity to SEQ ID NO: 9; optionally, a Woodchuck Hepatitis Virus Post-transcriptional Regulatory Element (WPRE) consisting of a nucleotide sequence having at least 90% sequence identity to SEQ ID NO: 10; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 90% sequence identity to SEQ ID NO: 11; and a 3’ ITR. In some embodiments, the polynucleotide comprises from 5’ to 3’: a 5’ ITR; a kidney-specific promoter consisting of a nucleotide sequence having at least 95% sequence identity to SEQ ID NO: 1; a regulatory element consisting of a nucleotide sequence having at least 95% sequence identity to SEQ ID NO: 7; a podocin coding sequence consisting of a nucleotide sequence having at least 95% sequence identity to SEQ ID NO: 9; optionally, a Woodchuck Hepatitis Virus Post-transcriptional Regulatory Element (WPRE) consisting of a nucleotide sequence having at least 95% sequence identity to SEQ ID NO: 10; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 95% sequence identity to SEQ ID NO: 11; and a 3’ ITR. In some embodiments, the polynucleotide comprises from 5’ to 3’: a 5’ ITR; a kidney-specific promoter consisting of a nucleotide sequence having at least 96% sequence identity to SEQ ID NO: 1; a regulatory element consisting of a nucleotide sequence having at least 96% sequence identity to SEQ ID NO: 7; a podocin coding sequence consisting of a nucleotide sequence having at least 96% sequence identity to SEQ ID NO: 9; optionally, a Woodchuck Hepatitis Virus Post-transcriptional Regulatory Element (WPRE) consisting of a nucleotide sequence having at least 96% sequence identity to SEQ ID NO: 10; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 96% sequence identity to SEQ ID NO: 11; and a 3’ ITR. In some embodiments, the polynucleotide comprises from 5’ to 3’: a 5’ ITR; a kidney-specific promoter consisting of a nucleotide sequence having at least 97% sequence identity to SEQ ID NO: 1; a regulatory element consisting of a nucleotide sequence having at least 97% sequence identity to SEQ ID NO: 7; a podocin coding sequence consisting of a nucleotide sequence having at least 97% sequence identity to SEQ ID NO: 9; optionally, a Woodchuck Hepatitis Virus Post-transcriptional Regulatory Element (WPRE) consisting of a nucleotide sequence having at least 97% sequence identity to SEQ ID NO: 10; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 97% sequence identity to SEQ ID NO: 11; and a 3’ ITR. In some embodiments, the polynucleotide comprises from 5’ to 3’: a 5’ ITR; a kidney-specific promoter consisting of a nucleotide sequence having at least 98% sequence identity to SEQ ID NO: 1; a regulatory element consisting of a nucleotide sequence having at least 98% sequence identity to SEQ ID NO: 7; a podocin coding sequence consisting of a nucleotide sequence having at least 98% sequence identity to SEQ ID NO: 9; optionally, a Woodchuck Hepatitis Virus Post-transcriptional Regulatory Element (WPRE) consisting of a nucleotide sequence having at least 98% sequence identity to SEQ ID NO: 10; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 98% sequence identity to SEQ ID NO: 11; and a 3’ ITR. In some embodiments, the polynucleotide comprises from 5’ to 3’: a 5’ ITR; a kidney-specific promoter consisting of a nucleotide sequence having at least 99% sequence identity to SEQ ID NO: 1; a regulatory element consisting of a nucleotide sequence having at least 99% sequence identity to SEQ ID NO: 7; a podocin coding sequence consisting of a nucleotide sequence having at least 99% sequence identity to SEQ ID NO: 9; optionally, a Woodchuck Hepatitis Virus Post-transcriptional Regulatory Element (WPRE) consisting of a nucleotide sequence having at least 99% sequence identity to SEQ ID NO: 10; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 99% sequence identity to SEQ ID NO: 11; and a 3’ ITR. In some embodiments, the polynucleotide comprises from 5’ to 3’: a 5’ ITR; a kidney-specific promoter consisting of a nucleotide sequence having 100% sequence identity to SEQ ID NO: 1; a regulatory element consisting of a nucleotide sequence having 100% sequence identity to SEQ ID NO: 7; a podocin coding sequence consisting of a nucleotide sequence having 100% sequence identity to SEQ ID NO: 9; optionally, a Woodchuck Hepatitis Virus Post- transcriptional Regulatory Element (WPRE) consisting of a nucleotide sequence having 100% sequence identity to SEQ ID NO: 10; optionally, a polyadenylation sequence consisting of a nucleotide sequence having 100% sequence identity to SEQ ID NO: 11; and a 3’ ITR. In some embodiments, the polynucleotide comprises from 5’ to 3’: a 5’ ITR; a kidney-specific promoter consisting of the nucleotide sequence of SEQ ID NO: 1; a regulatory element consisting of the nucleotide sequence of SEQ ID NO: 7; a podocin coding sequence consisting of the nucleotide sequence of SEQ ID NO: 9; optionally, a Woodchuck Hepatitis Virus Post- transcriptional Regulatory Element (WPRE) consisting of the nucleotide sequence of SEQ ID NO: 10; optionally, a polyadenylation sequence consisting of the nucleotide sequence of SEQ ID NO: 11; and a 3’ ITR. In preferred embodiments, the polynucleotide does not comprise any further regulatory elements or protein-coding sequences. Spacer sequences The polynucleotide may comprise one or more spacer sequences. The polynucleotide elements may be operably linked by one or more spacer sequences. As used herein, the term “operably linked” may mean that the elements described are in a relationship permitting them to function in their intended manner. As used herein, a “spacer sequence” may refer to any nucleotide sequence which is inserted between two elements, such that the elements are in a relationship permitting them to function in their intended manner. Suitably, spacer sequences may be included to provide a polynucleotide of a desired length. For example, for efficient encapsidation of AAV vectors, spacer sequences may be included if the expression cassette is less than 3.0 kb in length. Suitably, a spacer sequence has no function or activity. The length and sequence of a spacer sequence is not particularly limited. Suitably, a spacer sequence has a length of about 1000 bp or less, about 900 bp or less, about 800 bp or less, about 700 bp or less, about 600 bp or less, about 500 bp or less, about 400 bp or less, about 300 bp or less, about 200 bp or less, about 180 bp or less, about 160 bp or less, about 140 bp or less, about 120 bp or less, or about 100 bp or less. Suitably, a spacer sequence has a length of about 1 bp or more, about 2 bp or more, about 3 bp or more, about 4 bp or more, about 5 bp or more, or about 10 bp or more. Suitably, a spacer sequence has a length of about 1 bp to about 1000 bp, about 1 bp to about 500 bp, about 1 bp to about 200 bp, or about 10 bp to about 100 bp. Suitably, a spacer sequence has an arbitrary sequence that lacks function or activity (e.g. lacks binding sites) (see e.g. Estrada, J., et al., 2016. PloS one, 11(3), p.e0151740). Example spacer sequences based on random shuffled DNA sequences are provided below: Example spacer sequence Length gcaggtcacg (SEQ ID NO: 12)10bptcgaactggacatga (SEQ ID NO: 13)15bptgtcagaaaagcggtcat (SEQ ID NO: 14)18bptggcgtatatgccggcaaca (SEQ ID NO: 15)20bpccggatcggtaagagaaagctcatt (SEQ ID NO: 16)25bpacatacggtaccgggtcgaatggaatgcct (SEQ ID NO: 17)30bpgcttgtagatggccaattgagctcccaggcatgacttaat (SEQ ID NO: 18)40bpcataccccgtcttctggccaagtggcaagtctatgagcggtgtatgaacaaatcggtc 60bp at (SEQ ID NO: 19) gaactgaccgaattaccagccctctagaaaaccaagtagcaaagccaggtttcgccca 80bp tggctcatcgtcagctgaccgg (SEQ ID NO: 20) aaagacaaggagggggtgatgtcggcaggttaccacaccggcggaacatgatatttag 100bp aatgtacgccgcggttatccccccgttttaacctaacttcgt (SEQ ID NO: 21) Other example spacer sequences are provided below: Example spacer sequence Length cccggattattcataccgtcccaccatcgggcgcggatcccggtccgaagcgcgcggaa ttctgcagtcgacggtaccgcgggcccgggatccaccggtcgccacc (SEQ ID NO: 22) 106bp ccttaagggaaacctgtcgtgccagctgcattaatgaatcggaccggaattctcaaagg cctacgacgactggatccgccacc (SEQ ID NO: 23)83bpgaattcaaaggcctacgtcgactggatccggtaccgaggagatctgccgccgcgatcgc c (SEQ ID NO: 24)60bpgcttaagcttggtaccgagctcggatccactagtccagtgtggtgggtcgccacc 55bp (SEQ ID NO: 25) cccggattattcataccgtcccaccatcgggcgcggatcccggtccgaagcgcgcggaa ttcccctggg (SEQ ID NO: 26)69bpgaattcccctggg (SEQ ID NO: 27)13bpcttaagccctggg (SEQ ID NO: 28)13bpggccctggggaccggtccacc (SEQ ID NO: 29)21bpggccctggggaccggtcgccacc (SEQ ID NO: 30) 23bp ggccctgggaccggtcgccacc (SEQ ID NO: 31)22bptagacgactagtcatatgcctgcaggcatgcaagcttgatatcaagcttatcgat (SEQ ID NO: 32) 55 bp atccagcacagtggcggccgctcgagtctagagggcccgtttaaacccgctgatcagcc tcga (SEQ ID NO: 33) 63 bp In some embodiments, the polynucleotide comprises from 5’ to 3’: a 5’ ITR; a kidney-specific promoter; a first spacer sequence; a regulatory element comprising a spliceosomal intron or a fragment thereof comprising a branch point sequence, a polypyrimidine tract, and a 3’ splice acceptor site; a second spacer sequence; a protein-coding sequence encoding podocin; and a 3’ ITR. In some embodiments, the polynucleotide comprises from 5’ to 3’: a 5’ ITR; a kidney-specific promoter; a first spacer sequence; a regulatory element comprising a spliceosomal intron or a fragment thereof comprising a branch point sequence, a polypyrimidine tract, and a 3’ splice acceptor site; a second spacer sequence; a protein-coding sequence encoding podocin; a third spacer sequence; a Woodchuck Hepatitis Virus Post-transcriptional Regulatory Element (WPRE); and a 3’ ITR. In some embodiments, the polynucleotide comprises from 5’ to 3’: a 5’ ITR; a kidney-specific promoter; a first spacer sequence; a regulatory element comprising a spliceosomal intron or a fragment thereof comprising a branch point sequence, a polypyrimidine tract, and a 3’ splice acceptor site; a second spacer sequence; a protein-coding sequence encoding podocin; a third spacer sequence; a polyadenylation sequence; and a 3’ ITR. In some embodiments, the polynucleotide comprises from 5’ to 3’: a 5’ ITR; a kidney-specific promoter; a first spacer sequence; a regulatory element comprising a spliceosomal intron or a fragment thereof comprising a branch point sequence, a polypyrimidine tract, and a 3’ splice acceptor site; a second spacer sequence; a protein-coding sequence encoding podocin; a third spacer sequence; a Woodchuck Hepatitis Virus Post-transcriptional Regulatory Element (WPRE); a fourth spacer sequence; a polyadenylation sequence; and a 3’ ITR. In some embodiments, the polynucleotide comprises from 5’ to 3’: a 5’ ITR; a first spacer sequence; a kidney-specific promoter; a second spacer sequence; a regulatory element comprising a spliceosomal intron or a fragment thereof comprising a branch point sequence, a polypyrimidine tract, and a 3’ splice acceptor site; a third spacer sequence; a protein-coding sequence encoding podocin; a fourth spacer sequence; a Woodchuck Hepatitis Virus Post- transcriptional Regulatory Element (WPRE); a fifth spacer sequence; a polyadenylation sequence; a sixth spacer sequence; and a 3’ ITR. Example polynucleotide sequence In preferred embodiments, the polynucleotide does not comprise any further nucleotide sequences, except for spacer sequences. In some embodiments, a polynucleotide of the invention comprises a nucleotide sequence which is at least 70% identical to SEQ ID NO: 34. Suitably, the polynucleotide comprises a nucleotide sequence which is at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 34. In some embodiments, the polynucleotide comprises the nucleotide sequence SEQ ID NO: 34. cacctgaggtcaggagttcgagaccagcgtggccaacatgatgaaaccccgtctctagtaaa aatacaaaaattagccaggcatggtgctatatacctgtagcaccagctacttgggagacaga ggtgggagaattacttgaacctgggaggttcaagccatgggaggtggaagttgcagtgagcc gagatgccactgcactccagcctgagcaacagagcaagactatctcaagaaaagaaagaaag aaagaaagagacttgccaaggtcatgtatcagggcaaggaagagctgggggcccagctggct gctcccctgctgagctgggagaccaccttgatctgacttctcccatcttcccagcctaagcc aggccctggggtcacggaggctggggaggcaccgaggaacgcgcctggcatgtgctgacagg ggattttatgctccagctgggccagctgggaggagcctgctgggcagaggccagagctgggg gctctggaaggtacctgggggaggttgcactgtgagaatgagctcaagctgggtcagagagc agggctgactctgccagtgcctgcatcagcctcatcgctctcctaggctcctggcctgctgg actctgggctgcaggtccttcttgaaaggctgtgagtagtgagacaaggagcaggagtgagg ggtggcaggagagaagatagagattgagagagagagagagagagagacagagagagaggaag agacagagacaaaaggagagagaacggcttagacaaggagagaaagatggaaagataaagag actgggcgcagtggctcacgcctgtaatcccaacacttggggaggccaaggtgggaggatgg cttgaaggaaagagtctgagatcaacctggccaacatagtgagaccccgtctctaaaaaaaa aagaaaaaaaaaagaaaaaagaaaaaaaagtttttttaaagagacagagaaagagactcaga gattgagactgagagcaagacagagagagatactcacagggaagaggggaagaggaaaacga gaaagggaggagagtaacggaaagagataaaaaagaaaagcaggtggcagagacacacagag agggacccagagaaagccagacagacgcaggtggctggcagcgggcgctgtgggggtcacag tagggggacctgtg(n) agttctctcgttaacttaatgagacagatagaaactggtcttgt agaaacagagtagtcgcctgcttttctgccaggtgctgacttctctcccctgggcttttttc tttttctcagg(n) atggagaggagggcgcggagctcctccagggagtcccgcgggcgagg cggcaggactccgcacaaggagaacaagagggcaaaggccgagaggagcggcgggggccgcg ggcgccaggaggctgggcccgagccgtcgggctccggacgggcggggaccccgggggagccc cgagcgcccgccgccacggtggtggacgtggatgaggtccgaggctccggcgaggagggcac cgaggtggtggcgctgttggagagcgagcggcccgaggaaggtaccaaatcctccggcttag gggcctgtgagtggcttcttgtcctcatttccctgctcttcatcatcatgaccttccctttt tccatctggttctgcgtaaaggttgtacaagagtatgaaagagtaattatattccgactggg acatctgcttcctggaagagccaaaggccctggtcttttcttttttttgccctgcctggata cctaccacaaggttgaccttcgtctccaaactctggagataccttttcatgagatcgtgacc aaagacatgtttataatggagatagatgccatttgctactaccgaatggaaaatgcctctct tctcctaagcagtcttgctcatgtatctaaagctgtgcaattccttgtgcaaaccactatga agcgtctcctagcacatcgatccctcactgaaattcttctagagaggaagagcatcgcccaa gatgcaaaggttgccttggattcagtgacctgtatttggggaatcaaagtggagagaataga aattaaagatgtgaggttgccagctgggcttcagcactcactggctgtggaggctgaagcgc aaagacaagccaaagtgcggatgattgctgcagaagcggaaaaggctgcttctgagtccctg aggatggcagctgagattctgtcaggcacccctgctgctgttcagcttcgatacctccacac ccttcagtctctgtccacagagaagccttccactgtggttttacctttgccatttgacctac tgaattgcctgtcttctcccagcaacagaactcagggaagcctccccttcccaagtccttcc aaacctgttgagccactaaatcctaaaaagaaagactctcccatgtta(n) aatcaacctc tggattacaaaatttgtgaaagattgactggtattcttaactatgttgctccttttacgcta tgtggatacgctgctttaatgcctttgtatcatgctattgcttcccgtatggctttcatttt ctcctccttgtataaatcctggttgctgtctctttatgaggagttgtggcccgttgtcaggc aacgtggcgtggtgtgcactgtgtttgctgacgcaacccccactggttggggcattgccacc acctgtcagctcctttccgggactttcgctttccccctccctattgccacggcggaactcat cgccgcctgccttgcccgctgctggacaggggctcggctgttgggcactgacaattccgtgg tgttgtcggggaaatcatcgtcctttccttggctgctcgcctgtgttgccacctggattctg cgcgggacgtccttctgctacgtcccttcggccctcaatccagcggaccttccttcccgcgg cctgctgccggctctgcggcctcttccgcgtcttcgccttcgccctcagacgagtcggatct ccctttgggccgcctccccgc(n) ctgtgccttctagttgccagccatctgttgtttgccc ctcccccgtgccttccttgaccctggaaggtgccactcccactgtcctttcctaataaaatg aggaaattgcatcgcattgtctgagtaggtgtcattctattctggggggtggggtggggcag gacagcaagggggaggattgggaagacaatagcaggcatgctggggatgcggtgggctctat gg wherein x1 is from 0 to 100, x2 is from 0 to 100, x3 is from 0 to 100, and x4 is from 0 to 100 Example polynucleotide (SEQ ID NO: 34) In some embodiments, each of x1, x2, x3, and x4 is independently from 1 to 100, from 2 to 100, from 3 to 100, from 4 to 100, from 5 to 100, from 6 to 100, from 7 to 100, from 8 to 100, from 9 to 100, or from 10 to 100. In some embodiments, each of (n)x1, (n)x2, (n)x3, and (n)x4 is independently selected from any of SEQ ID NOs: 12-33. In some embodiments, (n)x1 is selected from any of SEQ ID NOs: 22- 33. In some embodiments, (n)x2 is selected from any of SEQ ID NOs: 22-33. In some embodiments, (n)x3 is selected from any of SEQ ID NOs: 22-33. In some embodiments, (n)x4 is selected from any of SEQ ID NOs: 22-33. In some embodiments, a polynucleotide of the invention comprises or consists of a nucleotide sequence which is at least 70% identical to SEQ ID NO: 54. Suitably, the polynucleotide comprises or consists of a nucleotide sequence which is at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 54. In some embodiments, the polynucleotide comprises or consists of the nucleotide sequence SEQ ID NO: 54. cctgcaggcagctgcgcgctcgctcgctcactgaggccgcccgggcaaagcccgggcgtcgg gcgacctttggtcgcccggcctcagtgagcgagcgagcgcgcagagagggagtggccaactc catcactaggggttcct(n) cacctgaggtcaggagttcgagaccagcgtggccaacatga tgaaaccccgtctctagtaaaaatacaaaaattagccaggcatggtgctatatacctgtagc accagctacttgggagacagaggtgggagaattacttgaacctgggaggttcaagccatggg aggtggaagttgcagtgagccgagatgccactgcactccagcctgagcaacagagcaagact atctcaagaaaagaaagaaagaaagaaagagacttgccaaggtcatgtatcagggcaaggaa gagctgggggcccagctggctgctcccctgctgagctgggagaccaccttgatctgacttct cccatcttcccagcctaagccaggccctggggtcacggaggctggggaggcaccgaggaacg cgcctggcatgtgctgacaggggattttatgctccagctgggccagctgggaggagcctgct gggcagaggccagagctgggggctctggaaggtacctgggggaggttgcactgtgagaatga gctcaagctgggtcagagagcagggctgactctgccagtgcctgcatcagcctcatcgctct cctaggctcctggcctgctggactctgggctgcaggtccttcttgaaaggctgtgagtagtg agacaaggagcaggagtgaggggtggcaggagagaagatagagattgagagagagagagaga gagagacagagagagaggaagagacagagacaaaaggagagagaacggcttagacaaggaga gaaagatggaaagataaagagactgggcgcagtggctcacgcctgtaatcccaacacttggg gaggccaaggtgggaggatggcttgaaggaaagagtctgagatcaacctggccaacatagtg agaccccgtctctaaaaaaaaaagaaaaaaaaaagaaaaaagaaaaaaaagtttttttaaag agacagagaaagagactcagagattgagactgagagcaagacagagagagatactcacaggg aagaggggaagaggaaaacgagaaagggaggagagtaacggaaagagataaaaaagaaaagc aggtggcagagacacacagagagggacccagagaaagccagacagacgcaggtggctggcag cgggcgctgtgggggtcacagtagggggacctgtg(n) agttctctcgttaacttaatgag acagatagaaactggtcttgtagaaacagagtagtcgcctgcttttctgccaggtgctgact tctctcccctgggcttttttctttttctcagg(n) atggagaggagggcgcggagctcctc cagggagtcccgcgggcgaggcggcaggactccgcacaaggagaacaagagggcaaaggccg agaggagcggcgggggccgcgggcgccaggaggctgggcccgagccgtcgggctccggacgg gcggggaccccgggggagccccgagcgcccgccgccacggtggtggacgtggatgaggtccg aggctccggcgaggagggcaccgaggtggtggcgctgttggagagcgagcggcccgaggaag gtaccaaatcctccggcttaggggcctgtgagtggcttcttgtcctcatttccctgctcttc atcatcatgaccttccctttttccatctggttctgcgtaaaggttgtacaagagtatgaaag agtaattatattccgactgggacatctgcttcctggaagagccaaaggccctggtcttttct tttttttgccctgcctggatacctaccacaaggttgaccttcgtctccaaactctggagata ccttttcatgagatcgtgaccaaagacatgtttataatggagatagatgccatttgctacta ccgaatggaaaatgcctctcttctcctaagcagtcttgctcatgtatctaaagctgtgcaat tccttgtgcaaaccactatgaagcgtctcctagcacatcgatccctcactgaaattcttcta gagaggaagagcatcgcccaagatgcaaaggttgccttggattcagtgacctgtatttgggg aatcaaagtggagagaatagaaattaaagatgtgaggttgccagctgggcttcagcactcac tggctgtggaggctgaagcgcaaagacaagccaaagtgcggatgattgctgcagaagcggaa aaggctgcttctgagtccctgaggatggcagctgagattctgtcaggcacccctgctgctgt tcagcttcgatacctccacacccttcagtctctgtccacagagaagccttccactgtggttt tacctttgccatttgacctactgaattgcctgtcttctcccagcaacagaactcagggaagc ctccccttcccaagtccttccaaacctgttgagccactaaatcctaaaaagaaagactctcc catgtta(n) aatcaacctctggattacaaaatttgtgaaagattgactggtattcttaac tatgttgctccttttacgctatgtggatacgctgctttaatgcctttgtatcatgctattgc ttcccgtatggctttcattttctcctccttgtataaatcctggttgctgtctctttatgagg agttgtggcccgttgtcaggcaacgtggcgtggtgtgcactgtgtttgctgacgcaaccccc actggttggggcattgccaccacctgtcagctcctttccgggactttcgctttccccctccc tattgccacggcggaactcatcgccgcctgccttgcccgctgctggacaggggctcggctgt tgggcactgacaattccgtggtgttgtcggggaaatcatcgtcctttccttggctgctcgcc tgtgttgccacctggattctgcgcgggacgtccttctgctacgtcccttcggccctcaatcc agcggaccttccttcccgcggcctgctgccggctctgcggcctcttccgcgtcttcgccttc gccctcagacgagtcggatctccctttgggccgcctccccgc(n) ctgtgccttctagttg ccagccatctgttgtttgcccctcccccgtgccttccttgaccctggaaggtgccactccca ctgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtaggtgtcattctatt ctggggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgc tggggatgcggtgggctctatgg(n) aggaacccctagtgatggagttggccactccctct ctgcgcgctcgctcgctcactgaggccgggcgaccaaaggtcgcccgacgcccgggctttgc ccgggcggcctcagtgagcgagcgagcgcgcagctgcctgcagg wherein x0 is from 0 to 1000, x1 is from 0 to 100, x2 is from 0 to 100, x3 is from 0 to 100, x4 is from 0 to 100, and x5 is from 0 to 1000 Example polynucleotide (SEQ ID NO: 54) In some embodiments, each of x1, x2, x3, and x4 is independently from 1 to 100, from 2 to 100, from 3 to 100, from 4 to 100, from 5 to 100, from 6 to 100, from 7 to 100, from 8 to 100, from 9 to 100, or from 10 to 100. In some embodiments, each of (n)x1, (n)x2, (n)x3, and (n)x4 is independently selected from any of SEQ ID NOs: 12-33. In some embodiments, (n)x1is selected from any of SEQ ID NOs: 22- 33. In some embodiments, (n)x2is selected from any of SEQ ID NOs: 22-33. In some embodiments, (n)x3is selected from any of SEQ ID NOs: 22-33. In some embodiments, (n)x4is selected from any of SEQ ID NOs: 22-33. In some embodiments, each of x0 and x5 is independently from 10 to 1000, from 50 to 1000, or from 100 to 1000. Adeno-associated viral (AAV) vectors The present invention provides a vector comprising the polynucleotide of the present invention. A “vector” is a tool that allows or facilitates the transfer of an entity from one environment to another. The four major types of vectors are plasmids, viral vectors, cosmids, and artificial chromosomes. In particular, the present invention provides an AAV vector comprising the polynucleotide of the present invention. The AAV vector of the present invention may be in the form of an AAV vector particle. Methods of preparing and modifying AAV vectors and AAV vector particles, are well known in the art. Suitable methods are described in Ayuso, E., et al., 2010. Current gene therapy, 10(6), pp.423-43. The AAV vector of the present invention may be capable of transducing kidney cells. In some embodiments, the AAV vector of the present invention is capable of specifically transducing kidney cells. The AAV vector of the present invention is preferably capable of transducing glomerular cells. In some embodiments, the AAV vector of the present invention is capable of specifically transducing glomerular cells. The AAV vector of the present invention is preferably capable of transducing podocytes. In some embodiments, the AAV vector of the present invention is capable of specifically transducing podocytes. AAV genome The AAV vector or AAV vector particle may comprise an AAV genome or a fragment or derivative thereof. An AAV genome is a polynucleotide sequence, which may encode functions needed for production of an AAV particle. These functions include those operating in the replication and packaging cycle of AAV in a host cell, including encapsidation of the AAV genome into an AAV particle. Naturally occurring AAVs are replication-deficient and rely on the provision of helper functions in trans for completion of a replication and packaging cycle. Accordingly, the AAV genome of the AAV vector of the invention is typically replication-deficient. The AAV genome may be in single-stranded form (ssAAV), either positive or negative-sense, or alternatively in double-stranded form (dsAAV). The use of a double-stranded form allows bypass of the DNA replication step in the target cell and so can accelerate transgene expression. The maximum packaging capacity of the single-stranded form is larger than the double-stranded form. Suitably, the AAV genome is in single-stranded form. AAVs occurring in nature may be classified according to various biological systems. The AAV genome may be from any naturally derived serotype, isolate or clade of AAV. AAV may be referred to in terms of their serotype. A serotype corresponds to a variant subspecies of AAV which, owing to its profile of expression of capsid surface antigens, has a distinctive reactivity which can be used to distinguish it from other variant subspecies. Typically, an AAV vector particle having a particular AAV serotype does not efficiently cross- react with neutralising antibodies specific for any other AAV serotype. AAV serotypes include AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAV10 and AAV11, and derivatives thereof. AAV may also be referred to in terms of clades or clones. This refers to the phylogenetic relationship of naturally derived AAVs, and typically to a phylogenetic group of AAVs which can be traced back to a common ancestor, and includes all descendants thereof. Additionally, AAVs may be referred to in terms of a specific isolate, i.e. a genetic isolate of a specific AAV found in nature. The term genetic isolate describes a population of AAVs which has undergone limited genetic mixing with other naturally occurring AAVs, thereby defining a recognisably distinct population at a genetic level. Typically, the AAV genome of a naturally derived serotype, isolate or clade of AAV comprises at least one inverted terminal repeat sequence (ITR). An ITR sequence acts in cis to provide a functional origin of replication and allows for integration and excision of the vector from the genome of a cell. ITRs may be the only sequences required in cis next to the therapeutic gene. The AAV genome may also comprise packaging genes, such as rep and / or cap genes which encode packaging functions for an AAV particle. A promoter may be operably linked to each of the packaging genes. Specific examples of such promoters include the p5, p19 and p40 promoters. For example, the p5 and p19 promoters are generally used to express the rep gene, while the p40 promoter is generally used to express the cap gene. The rep gene encodes one or more of the proteins Rep78, Rep68, Rep52 and Rep40 or variants thereof. The cap gene encodes one or more capsid proteins such as VP1, VP2 and VP3 or variants thereof. These proteins make up the capsid of an AAV particle, which determines the AAV serotype. VP1, VP2, and VP3 may be produced by alternate mRNA splicing (Trempe, J.P. and Carter, B.J., 1988. Journal of virology, 62(9), pp.3356-3363). Thus, VP1, VP2 and VP3 may have identical sequences, but wherein VP2 is truncated at the N-terminus relative to VP1, and VP3 is truncated at the N-terminus relative to VP2. The AAV genome may be the full genome of a naturally occurring AAV. For example, a vector comprising a full AAV genome may be used to prepare an AAV vector or vector particle. Preferably, the AAV genome is derivatised for the purpose of administration to patients. Such derivatisation is standard in the art and the invention encompasses the use of any known derivative of an AAV genome, and derivatives which could be generated by applying techniques known in the art. The AAV genome may be a derivative of any naturally occurring AAV. Suitably, the AAV genome is a derivative of AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAV10, or AAV11. Suitably, the AAV genome is a derivative of AAV2. Derivatives of an AAV genome include any truncated or modified forms of an AAV genome which allow for expression of a transgene from an AAV vector of the invention in vivo. Typically, it is possible to truncate the AAV genome significantly to include minimal viral sequence yet retain the above function. This is preferred for safety reasons to reduce the risk of recombination of the vector with wild-type virus, and also to avoid triggering a cellular immune response by the presence of viral gene proteins in the target cell. Typically, a derivative will include at least one inverted terminal repeat sequence (ITR), preferably more than one ITR, such as two ITRs or more. One or more of the ITRs may be derived from AAV genomes having different serotypes, or may be a chimeric or mutant ITR. A preferred mutant ITR is one having a deletion of a trs (terminal resolution site). This deletion allows for continued replication of the genome to generate a single-stranded genome which contains both coding and complementary sequences, i.e. a self-complementary AAV (scAAV) genome. This allows for bypass of DNA replication in the target cell, and so enables accelerated transgene expression. However, the maximum packaging capacity of a scAAV is reduced. Suitably, the AAV genome is not a scAAV genome. The AAV genome may comprise one or more ITR sequences from any naturally derived serotype, isolate or clade of AAV or a variant thereof. The AAV genome may comprise at least one, such as two, AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAV10, or AAV11 ITRs, or variants thereof. Suitably, the AAV genome may comprise at least one, such as two, AAV2 ITRs. The inclusion of one or more ITRs is preferred to aid concatamer formation of the AAV vector in the nucleus of a host cell, for example following the conversion of single-stranded vector DNA into double-stranded DNA by the action of host cell DNA polymerases. The formation of such episomal concatamers protects the AAV vector during the life of the host cell, thereby allowing for prolonged expression of the transgene in vivo. Suitably, ITR elements will be the only sequences retained from the native AAV genome in the derivative. A derivative will preferably not include the rep and / or cap genes of the native genome and any other sequences of the native genome. This is preferred for the reasons described above, and also to reduce the possibility of integration of the vector into the host cell genome. Additionally, reducing the size of the AAV genome allows for increased flexibility in incorporating other sequence elements (such as regulatory elements) within the vector in addition to the protein-coding sequence. The following portions could therefore be removed in a derivative of the invention: one inverted terminal repeat (ITR) sequence, the replication (rep) and capsid (cap) genes. However, derivatives may additionally include one or more rep and / or cap genes or other viral sequences of an AAV genome. Naturally occurring AAV integrates with a high frequency at a specific site on human chromosome 19, and shows a negligible frequency of random integration, such that retention of an integrative capacity in the AAV vector may be tolerated in a therapeutic setting. The invention additionally encompasses the provision of sequences of an AAV genome in a different order and configuration to that of a native AAV genome. The invention also encompasses the replacement of one or more AAV sequences or genes with sequences from another virus or with chimeric genes composed of sequences from more than one virus. Such chimeric genes may be composed of sequences from two or more related viral proteins of different viral species. AAV serotype and capsid proteins The AAV vector particle may be encapsidated by capsid proteins. The serotype may facilitate the transduction of glomerular cells (e.g. podocytes), for example specific transduction of glomerular cells (e.g. podocytes). The AAV vector particle may be a kidney-specific vector particle. Preferably, the AAV vector particle is a glomerular-specific (e.g. podocyte-specific) vector particle. The AAV vector particle may be encapsidated by a glomerular-specific (e.g. podocyte-specific) capsid. The AAV vector particle may comprise a glomerular-specific (e.g. podocyte-specific) capsid protein. Suitably, the AAV vector particles may be transcapsidated forms wherein an AAV genome or derivative having an ITR of one serotype is packaged in the capsid of a different serotype. The AAV vector particle also includes mosaic forms wherein a mixture of unmodified capsid proteins from two or more different serotypes makes up the viral capsid. The AAV vector particle also includes chemically modified forms bearing ligands adsorbed to the capsid surface. For example, such ligands may include antibodies for targeting a particular cell surface receptor. Where a derivative comprises capsid proteins i.e. VP1, VP2 and / or VP3, the derivative may be a chimeric, shuffled or capsid-modified derivative of one or more naturally occurring AAVs. In particular, the invention encompasses the provision of capsid protein sequences from different serotypes, clades, clones, or isolates of AAV within the same vector (i.e. a pseudotyped vector). The AAV vector may be in the form of a pseudotyped AAV vector particle. Chimeric, shuffled or capsid-modified derivatives will be typically selected to provide one or more desired functionalities for the AAV vector. Thus, these derivatives may display increased efficiency of gene delivery, decreased immunogenicity (humoral or cellular), an altered tropism range and / or improved targeting of podocytes compared to an AAV vector comprising a naturally occurring AAV genome. Increased efficiency of gene delivery may be effected by improved receptor or co-receptor binding at the cell surface, improved internalisation, improved trafficking within the cell and into the nucleus, improved uncoating of the viral particle and improved conversion of a single-stranded genome to double-stranded form. Increased efficiency may also relate to an altered tropism range or targeting of podocytes, such that the vector dose is not diluted by administration to tissues where it is not needed. Chimeric capsid proteins include those generated by recombination between two or more capsid coding sequences of naturally occurring AAV serotypes. This may be performed for example by a marker rescue approach in which non-infectious capsid sequences of one serotype are co-transfected with capsid sequences of a different serotype, and directed selection is used to select for capsid sequences having desired properties. The capsid sequences of the different serotypes can be altered by homologous recombination within the cell to produce novel chimeric capsid proteins. Chimeric capsid proteins also include those generated by engineering of capsid protein sequences to transfer specific capsid protein domains, surface loops or specific amino acid residues between two or more capsid proteins, for example between two or more capsid proteins of different serotypes. Shuffled or chimeric capsid proteins may also be generated by DNA shuffling or by error-prone PCR. Hybrid AAV capsid genes can be created by randomly fragmenting the sequences of related AAV genes e.g. those encoding capsid proteins of multiple different serotypes and then subsequently reassembling the fragments in a self-priming polymerase reaction, which may also cause crossovers in regions of sequence homology. A library of hybrid AAV genes created in this way by shuffling the capsid genes of several serotypes can be screened to identify viral clones having a desired functionality. Similarly, error prone PCR may be used to randomly mutate AAV capsid genes to create a diverse library of variants which may then be selected for a desired property. The sequences of the capsid genes may also be genetically modified to introduce specific deletions, substitutions or insertions with respect to the native wild-type sequence. In particular, capsid genes may be modified by the insertion of a sequence of an unrelated protein or peptide within an open reading frame of a capsid coding sequence, or at the N- and / or C-terminus of a capsid coding sequence. The unrelated protein or peptide may advantageously be one which acts as a ligand for a particular cell type, thereby conferring improved binding to a target cell or improving the specificity of targeting of the vector to a particular cell population. The unrelated protein may also be one which assists purification of the viral particle as part of the production process, i.e. an epitope or affinity tag. The site of insertion will typically be selected so as not to interfere with other functions of the viral particle e.g. internalisation, trafficking of the viral particle. The capsid protein may be an artificial or mutant capsid protein. The term “artificial capsid” as used herein means that the capsid particle comprises an amino acid sequence which does not occur in nature or which comprises an amino acid sequence which has been engineered (e.g. modified) from a naturally occurring capsid amino acid sequence. In other words the artificial capsid protein comprises a mutation or a variation in the amino acid sequence compared to the sequence of the parent capsid from which it is derived where the artificial capsid amino acid sequence and the parent capsid amino acid sequences are aligned. The capsid protein may comprise a mutation or modification relative to the wild type capsid protein which improves the ability to transduce podocytes relative to an unmodified or wild type viral particle. Improved ability to transduce podocytes may be measured for example by measuring the expression of a reporter transgene, e.g. GFP, carried by the AAV vector particle, wherein expression of the transgene in podocytes correlates with the ability of the AAV vector particle to transduce podocytes. The AAV vector particle may be an AAV3B, LK03, AAV9, ShH10, AAV-DJ, AAV2, AAV6.2, AAV5, or AAV8 vector particle. In some embodiments, the AAV vector particle is an AAV3B vector particle or an LK03 vector particle. In one embodiment, the AAV vector particle is an LK03 vector particle. In other embodiments, the AAV vector particle is a ShH10, AAV-DJ, AAV2, AAV6.2, or AAV5 vector particle. The AAV vector particle may comprise an AAV3B, LK03, AAV9, ShH10, AAV-DJ, AAV2, AAV6.2, AAV5, or AAV8 capsid protein. In some embodiments, the AAV vector particle comprises an AAV3B capsid protein or an LK03 capsid protein. In one embodiment, the AAV vector particle comprises an LK03 capsid protein. In other embodiments, the AAV vector particle comprises a ShH10, AAV-DJ, AAV2, AAV6.2, or AAV5 capsid protein. The AAV vector particle may comprise AAV3B, LK03, AAV9, ShH10, AAV-DJ, AAV2, AAV6.2, AAV5, or AAV8 capsid proteins VP1, VP2 and VP3. In some embodiments, the AAV vector particle comprises AAV3B or LK03 capsid proteins VP1, VP2 and VP3. In one embodiment, the AAV vector particle comprises LK03 capsid proteins VP1, VP2 and VP3. In other embodiments, the AAV vector particle comprises ShH10, AAV-DJ, AAV2, AAV6.2, or AAV5 capsid proteins VP1, VP2 and VP3. The AAV vector particle may comprise one or more AAV2 ITR sequences and AAV3B capsid proteins, LK03 capsid proteins, AAV9 capsid proteins, ShH10 capsid proteins, AAV-DJ capsid proteins, AAV2 capsid proteins, AAV6.2 capsid proteins, AAV5 capsid proteins, or AAV8 capsid proteins. In some embodiments, the AAV vector particle comprises one or more AAV2 ITR sequences and AAV3B or LK03 capsid proteins. In other embodiments, the AAV vector particle comprises one or more AAV2 ITR sequences and ShH10, AAV-DJ, AAV2, AAV6.2, or AAV5 capsid proteins. The AAV vector particle may have an AAV2 genome and AAV3B capsid proteins (AAV2 / 3B), an AAV2 genome and LK03 capsid proteins, an AAV2 genome and AAV9 capsid proteins (AAV2 / 9), an AAV2 genome and ShH10 capsid proteins, an AAV2 genome and AAV-DJ capsid proteins, an AAV2 genome and AAV2 capsid proteins, an AAV2 genome and AAV6.2 capsid proteins, an AAV2 genome and AAV5 capsid proteins, or an AAV2 genome and AAV8 capsid proteins (AAV2 / 8). The nomenclature AAVX / Y may denote a pseudotyped AAV, for example where the ITR sequences are from AAVX and flank a cassette harbouring a payload which is encapsidated into serotype AAVY (i.e. with AAVY capsid proteins). AAV3B serotype The AAV vector particle may comprise an AAV3B capsid protein. Suitably, the AAV vector particle may be encapsidated by AAV3B capsid proteins. Two distinct AAV3 isolates (AAV3A and AAV3B) have been cloned. In comparison with vectors based on other AAV serotypes, it is thought that AAV3 vectors inefficiently transduce most cell types. However, AAV3B may efficiently transduce podocytes. AA3B has been described in Rutledge, E.A., et al., 1998. Journal of virology, 72(1), pp.309-319. The AAV vector particle may comprise an AAV3B VP1 capsid protein, an AAV3B VP2 capsid protein, and / or an AAV3B VP3 capsid protein. Suitably, the AAV vector particle may be encapsidated by AAV3B VP1 capsid proteins, AAV3B VP2 capsid proteins, and / or AAV3B VP3 capsid proteins. Suitably, the AAV vector particle may be encapsidated by AAV3B VP1, VP2, and VP3 capsid proteins. Suitably, the AAV3B VP1 capsid protein may comprise or consist of the amino acid sequence shown as SEQ ID NO: 35, or a variant which is at least 90% identical to SEQ ID NO: 35. MAADGYLPDWLEDNLSEGIREWWALKPGVPQPKANQQHQDNRRGLVLPGYKYLGPGNGLDKG EPVNEADAAALEHDKAYDQQLKAGDNPYLKYNHADAEFQERLQEDTSFGGNLGRAVFQAKKR ILEPLGLVEEAAKTAPGKKRPVDQSPQEPDSSSGVGKSGKQPARKRLNFGQTGDSESVPDPQ PLGEPPAAPTSLGSNTMASGGGAPMADNNEGADGVGNSSGNWHCDSQWLGDRVITTSTRTWA LPTYNNHLYKQISSQSGASNDNHYFGYSTPWGYFDFNRFHCHFSPRDWQRLINNNWGFRPKK LSFKLFNIQVKEVTQNDGTTTIANNLTSTVQVFTDSEYQLPYVLGSAHQGCLPPFPADVFMV PQYGYLTLNNGSQAVGRSSFYCLEYFPSQMLRTGNNFQFSYTFEDVPFHSSYAHSQSLDRLM NPLIDQYLYYLNRTQGTTSGTTNQSRLLFSQAGPQSMSLQARNWLPGPCYRQQRLSKTANDN NNSNFPWTAASKYHLNGRDSLVNPGPAMASHKDDEEKFFPMHGNLIFGKEGTTASNAELDNV MITDEEEIRTTNPVATEQYGTVANNLQSSNTAPTTRTVNDQGALPGMVWQDRDVYLQGPIWA KIPHTDGHFHPSPLMGGFGLKHPPPQIMIKNTPVPANPPTTFSPAKFASFITQYSTGQVSVE IEWELQKENSKRWNPEIQYTSNYNKSVNVDFTVDTNGVYSEPRPIGTRYLTRNL Example AAV3B VP1 capsid protein (SEQ ID NO: 35) Suitably, the variant may be at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identical to SEQ ID NO: 35. Suitably, the AAV3B VP2 and VP3 capsid proteins may be N-terminal truncations of SEQ ID NO: 35, or N-terminal truncations of a variant which is at least 90% identical, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identical to SEQ ID NO: 35. LK03 serotype The AAV vector particle may comprise an LK03 capsid protein. Suitably, the AAV vector particle may be encapsidated by LK03 capsid proteins. The AAV-LK03 cap sequence consists of fragments from seven different wild-type serotypes (AAV1, 2, 3B, 4, 6, 8, 9) and is described in Lisowski, L., et al., 2014. Nature, 506(7488), pp.382-386. The present inventors have demonstrated that AAV-LK03 vectors can achieve high transduction in human podocytes in vitro. The AAV vector particle may comprise an LK03 VP1 capsid protein, an LK03 VP2 capsid protein, and / or an LK03 VP3 capsid protein. Suitably, the AAV vector particle may be encapsidated by LK03 VP1 capsid proteins, LK03 VP2 capsid proteins, and / or LK03 VP3 capsid proteins. Suitably, the AAV vector particle may be encapsidated by LK03 VP1, VP2, and VP3 capsid proteins. Suitably, the LK03 VP1 capsid protein may comprise or consist of the amino acid sequence shown as SEQ ID NO: 36, or a variant which is at least 90% identical to SEQ ID NO: 36. MAADGYLPDWLEDNLSEGIREWWALQPGAPKPKANQQHQDNARGLVLPGYKYLGPGNGLDKG EPVNAADAAALEHDKAYDQQLKAGDNPYLKYNHADAEFQERLKEDTSFGGNLGRAVFQAKKR LLEPLGLVEEAAKTAPGKKRPVDQSPQEPDSSSGVGKSGKQPARKRLNFGQTGDSESVPDPQ PLGEPPAAPTSLGSNTMASGGGAPMADNNEGADGVGNSSGNWHCDSQWLGDRVITTSTRTWA LPTYNNHLYKQISSQSGASNDNHYFGYSTPWGYFDFNRFHCHFSPRDWQRLINNNWGFRPKK LSFKLFNIQVKEVTQNDGTTTIANNLTSTVQVFTDSEYQLPYVLGSAHQGCLPPFPADVFMV PQYGYLTLNNGSQAVGRSSFYCLEYFPSQMLRTGNNFQFSYTFEDVPFHSSYAHSQSLDRLM NPLIDQYLYYLNRTQGTTSGTTNQSRLLFSQAGPQSMSLQARNWLPGPCYRQQRLSKTANDN NNSNFPWTAASKYHLNGRDSLVNPGPAMASHKDDEEKFFPMHGNLIFGKEGTTASNAELDNV MITDEEEIRTTNPVATEQYGTVANNLQSSNTAPTTRTVNDQGALPGMVWQDRDVYLQGPIWA KIPHTDGHFHPSPLMGGFGLKHPPPQIMIKNTPVPANPPTTFSPAKFASFITQYSTGQVSVE IEWELQKENSKRWNPEIQYTSNYNKSVNVDFTVDTNGVYSEPRPIGTRYLTRPL Example LK03 VP1 capsid protein (SEQ ID NO: 36) Suitably, the variant may be at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identical to SEQ ID NO: 36. Suitably, the LK03 VP2 and VP3 capsid proteins may be N-terminal truncations of SEQ ID NO: 36, or N-terminal truncations of a variant which is at least 90% identical, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identical to SEQ ID NO: 36. AAV9 serotype The AAV vector particle may comprise an AAV9 capsid protein. Suitably, the AAV vector particle may be encapsidated by AAV9 capsid proteins. The present inventors have demonstrated that AAV9 vectors can achieve high transduction in human podocytes in vivo. The AAV vector particle may comprise an AAV9 VP1 capsid protein, an AAV9 VP2 capsid protein, and / or an AAV9 VP3 capsid protein. Suitably, the AAV vector particle may be encapsidated by AAV9 VP1 capsid proteins, AAV9 VP2 capsid proteins, and / or AAV9 VP3 capsid proteins. Suitably, the AAV vector particle may be encapsidated by AAV9 VP1, VP2, and VP3 capsid proteins. Suitably, the AAV9 VP1 capsid protein may comprise or consist of the amino acid sequence shown as SEQ ID NO: 37, or a variant which is at least 90% identical to SEQ ID NO: 37. MAADGYLPDWLEDNLSEGIREWWALKPGAPQPKANQQHQDNARGLVLPGYKYLGPGNGLDKG EPVNAADAAALEHDKAYDQQLKAGDNPYLKYNHADAEFQERLKEDTSFGGNLGRAVFQAKKR LLEPLGLVEEAAKTAPGKKRPVEQSPQEPDSSAGIGKSGAQPAKKRLNFGQTGDTESVPDPQ PIGEPPAAPSGVGSLTMASGGGAPVADNNEGADGVGSSSGNWHCDSQWLGDRVITTSTRTWA LPTYNNHLYKQISNSTSGGSSNDNAYFGYSTPWGYFDFNRFHCHFSPRDWQRLINNNWGFRP KRLNFKLFNIQVKEVTDNNGVKTIANNLTSTVQVFTDSDYQLPYVLGSAHEGCLPPFPADVF MIPQYGYLTLNDGSQAVGRSSFYCLEYFPSQMLRTGNNFQFSYEFENVPFHSSYAHSQSLDR LMNPLIDQYLYYLSKTINGSGQNQQTLKFSVAGPSNMAVQGRNYIPGPSYRQQRVSTTVTQN NNSEFAWPGASSWALNGRNSLMNPGPAMASHKEGEDRFFPLSGSLIFGKQGTGRDNVDADKV MITNEEEIKTTNPVATESYGQVATNHQSAQAQAQTGWVQNQGILPGMVWQDRDVYLQGPIWA KIPHTDGNFHPSPLMGGFGMKHPPPQILIKNTPVPADPPTAFNKDKLNSFITQYSTGQVSVE IEWELQKENSKRWNPEIQYTSNYYKSNNVEFAVNTEGVYSEPRPIGTRYLTRNL Example AAV9 VP1 capsid protein (SEQ ID NO: 37) Suitably, the variant may be at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identical to SEQ ID NO: 37. Suitably, the AAV9 VP2 and VP3 capsid proteins may be N-terminal truncations of SEQ ID NO: 37, or N-terminal truncations of a variant which is at least 90% identical, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identical to SEQ ID NO: 37. ShH10 serotype The AAV vector particle may comprise a ShH10 capsid protein. Suitably, the AAV vector particle may be encapsidated by ShH10 capsid proteins. The ShH10 variant is derived from AAV6 and has increased specificity and efficiency for Müller cells (see e.g. Klimczak, R.R., et al., 2009. PloS one, 4(10), p.e7467). The AAV vector particle may comprise a ShH10 VP1 capsid protein, a ShH10 VP2 capsid protein, and / or a ShH10 VP3 capsid protein. Suitably, the AAV vector particle may be encapsidated by ShH10 VP1 capsid proteins, ShH10 VP2 capsid proteins, and / or ShH10 VP3 capsid proteins. Suitably, the AAV vector particle may be encapsidated by ShH10 VP1, VP2, and VP3 capsid proteins. Suitably, the ShH10 VP1 capsid protein may comprise or consist of the amino acid sequence shown as SEQ ID NO: 38, or a variant which is at least 90% identical to SEQ ID NO: 38. MAADGYLPDWLEDNEGIREWWDLKPGAPLKSPKANQQKQDDGRGLVLPGYKYLGPFNGLDKG EPVNAADAAALEHDKAYDQQLKAGDNPYLRYNHADAEFQERLQEDTSFGGNLGRAVFQAKKR VLEPFGLVEEGAKTAPGKKRPVEQSPQEPDSSSGIGKTGQQPAKKRLNFGQTGDSESVPDPQ PLGEPPATPAAVGPTTMASGGGAPMADNNEGADGVGNASGNWHCDSTWLGDRVITTSTRTWA LPTYNNHLYKQISSASTGASNDNHYFGYSTPWGYFDFNRFHCHFSPRDWQRLINNNWGFRPK RLNFKLFNVQVKEVTTNDGVTTIANNLTSTVQVFSDSEYQLPYVLGSAHQGCLPPFPADVFM IPQYGYLTLNNGSQAVGRSSFYCLEYFPSQMLRTGNNFTFSYTFEDVPFHSSYAHSQSLDRL MNPLIDQYLYYLNRTQDQSGSAQNKDLLFSRGSPAGMSVQPKNWLPGPCYRQQRVSKTKTDN NNSNFTWTGASKYNLNGRESIINPGTAMASHKDDKNKFFPMSGVMIFGKESAGASNTALDNV MITDEEEIKATNPVATERFGTVAVNLQSSSTDPATGDVHVMGALPGMVWQDRDVYLQGPIWA KIPHTDGHFHPSPLMGGFGLKNPPPQILIKNTPVPANPPAEFSATKFASFITQYSTGQVSVE IEWELQKENSKRWNPEVQYTSNYAKSANVDFTVDNNGLYTEPRPIGTRYLTRPL Example ShH10 VP1 capsid protein (SEQ ID NO: 38) Suitably, the variant may be at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identical to SEQ ID NO: 38. Suitably, the ShH10 VP2 and VP3 capsid proteins may be N-terminal truncations of SEQ ID NO: 38, or N-terminal truncations of a variant which is at least 90% identical, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identical to SEQ ID NO: 38. AAV-DJ serotype The AAV vector particle may comprise an AAV-DJ capsid protein. Suitably, the AAV vector particle may be encapsidated by AAV-DJ capsid proteins. AAV-DJ is a hybrid vector created from DNA shuffling of eight AAV serotypes, which mediates efficient gene expression both in vitro and in vivo (see e.g. Mao, Y., et al., 2016. BMC biotechnology, 16, pp.1-8). The AAV vector particle may comprise an AAV-DJ VP1 capsid protein, an AAV-DJ VP2 capsid protein, and / or an AAV-DJ VP3 capsid protein. Suitably, the AAV vector particle may be encapsidated by AAV-DJ VP1 capsid proteins, AAV-DJ VP2 capsid proteins, and / or AAV-DJ VP3 capsid proteins. Suitably, the AAV vector particle may be encapsidated by AAV-DJ VP1, VP2, and VP3 capsid proteins. Suitably, the AAV-DJ VP1 capsid protein may comprise or consist of the amino acid sequence shown as SEQ ID NO: 39, or a variant which is at least 90% identical to SEQ ID NO: 39. MAADGYLPDWLEDTLSEGIRQWWKLKPGPPPPKPAERHKDDSRGLVLPGYKYLGPFNGLDKG EPVNEADAAALEHDKAYDRQLDSGDNPYLKYNHADAEFQERLKEDTSFGGNLGRAVFQAKKR LLEPLGLVEEAAKTAPGKKRPVEHSPVEPDSSSGTGKAGQQPARKRLNFGQTGDADSVPDPQ PIGEPPAAPSGVGSLTMAAGGGAPMADNNEGADGVGNSSGNWHCDSTWMGDRVITTSTRTWA LPTYNNHLYKQISNSTSGGSSNDNAYFGYSTPWGYFDFNRFHCHFSPRDWQRLINNNWGFRP KRLSFKLFNIQVKEVTQNEGTKTIANNLTSTIQVFTDSEYQLPYVLGSAHQGCLPPFPADVF MIPQYGYLTLNNGSQAVGRSSFYCLEYFPSQMLKTGNNFQFTYTFEDVPFHSSYAHSQSLDR LMNPLIDQYLYYLSRTQTTGGTTNTQTLGFSQGGPNTMANQAKNWLPGPCYRQQRVSKTSAD NNNSEYSWTGATKYHLNGRDSLVNPGPAMASHKDDEEKFFPQSGVLIFGKQGSEKTNVDIEK VMITDEEEIRTTNPVATEQYGSVSTNLQRGNRQAATADVNTQGVLPGMVWQDRDVYLQGPIW AKIPHTDGHFHPSPLMGGFGLKHPPPQILIKNTPVPADPPTTFNQSKLNSFITQYSTGQVSV EIEWELQKENSKRWNPEIQYTSNYYKSTSVDFAVNTEGVYSEPRPIGTRYLTRNL Example AAV-DJ VP1 capsid protein (SEQ ID NO: 39) Suitably, the variant may be at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identical to SEQ ID NO: 39. Suitably, the AAV-DJ VP2 and VP3 capsid proteins may be N-terminal truncations of SEQ ID NO: 39, or N-terminal truncations of a variant which is at least 90% identical, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identical to SEQ ID NO: 39. AAV2 serotype The AAV vector particle may comprise an AAV2 capsid protein. Suitably, the AAV vector particle may be encapsidated by AAV2 capsid proteins. The AAV vector particle may comprise an AAV2 VP1 capsid protein, an AAV2 VP2 capsid protein, and / or an AAV2 VP3 capsid protein. Suitably, the AAV vector particle may be encapsidated by AAV2 VP1 capsid proteins, AAV2 VP2 capsid proteins, and / or AAV2 VP3 capsid proteins. Suitably, the AAV vector particle may be encapsidated by AAV2 VP1, VP2, and VP3 capsid proteins. Suitably, the AAV2 VP1 capsid protein may comprise or consist of the amino acid sequence shown as SEQ ID NO: 40, or a variant which is at least 90% identical to SEQ ID NO: 40. MAADGYLPDWLEDTLSEGIRQWWKLKPGPPPPKPAERHKDDSRGLVLPGYKYLGPFNGLDKG EPVNEADAAALEHDKAYDRQLDSGDNPYLKYNHADAEFQERLKEDTSFGGNLGRAVFQAKKR VLEPLGLVEEPVKTAPGKKRPVEHSPVEPDSSSGTGKAGQQPARKRLNFGQTGDADSVPDPQ PLGQPPAAPSGLGTNTMATGSGAPMADNNEGADGVGNSSGNWHCDSTWMGDRVITTSTRTWA LPTYNNHLYKQISSQSGASNDNHYFGYSTPWGYFDFNRFHCHFSPRDWQRLINNNWGFRPKR LNFKLFNIQVKEVTQNDGTTTIANNLTSTVQVFTDSEYQLPYVLGSAHQGCLPPFPADVFMV PQYGYLTLNNGSQAVGRSSFYCLEYFPSQMLRTGNNFTFSYTFEDVPFHSSYAHSQSLDRLM NPLIDQYLYYLSRTNTPSGTTTQSRLQFSQAGASDIRDQSRNWLPGPCYRQQRVSKTSADNN NSEYSWTGATKYHLNGRDSLVNPGPAMASHKDDEEKFFPQSGVLIFGKQGSEKTNVDIEKVM ITDEEEIRTTNPVATEQYGSVSTNLQRGNRQAATADVNTQGVLPGMVWQDRDVYLQGPIWAK IPHTDGHFHPSPLMGGFGLKHPPPQILIKNTPVPANPSTTFSAAKFASFITQYSTGQVSVEI EWELQKENSKRWNPEIQYTSNYNKSVNRGLTVDTNGVYSEPRPIGTRYLTRNL Example AAV2 VP1 capsid protein (SEQ ID NO: 40) Suitably, the variant may be at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identical to SEQ ID NO: 40. Suitably, the AAV2 VP2 and VP3 capsid proteins may be N-terminal truncations of SEQ ID NO: 40, or N-terminal truncations of a variant which is at least 90% identical, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identical to SEQ ID NO: 40. AAV6.2 serotype The AAV vector particle may comprise an AAV6.2 capsid protein. Suitably, the AAV vector particle may be encapsidated by AAV6.2 capsid proteins. The AAV6.2 vector mutant was created by mutating the phenyalanine (F) residue at position 129 in AAV6 to leucine (L) (see e.g. Limberis, M.P., et al., 2009. Molecular Therapy, 17(2), pp.294-301). The AAV vector particle may comprise an AAV6.2 VP1 capsid protein, an AAV6.2 VP2 capsid protein, and / or an AAV6.2 VP3 capsid protein. Suitably, the AAV vector particle may be encapsidated by AAV6.2 VP1 capsid proteins, AAV6.2 VP2 capsid proteins, and / or AAV6.2 VP3 capsid proteins. Suitably, the AAV vector particle may be encapsidated by AAV6.2 VP1, VP2, and VP3 capsid proteins. Suitably, the AAV6.2 VP1 capsid protein may comprise or consist of the amino acid sequence shown as SEQ ID NO: 41, or a variant which is at least 90% identical to SEQ ID NO: 41. MAADGYLPDWLEDNLSEGIREWWDLKPGAPKPKANQQKQDDGRGLVLPGYKYLGPFNGLDKG EPVNAADAAALEHDKAYDQQLKAGDNPYLRYNHADAEFQERLQEDTSFGGNLGRAVFQAKKR VLEPLGLVEEGAKTAPGKKRPVEQSPQEPDSSSGIGKTGQQPAKKRLNFGQTGDSESVPDPQ PLGEPPATPAAVGPTTMASGGGAPMADNNEGADGVGNASGNWHCDSTWLGDRVITTSTRTWA LPTYNNHLYKQISSASTGASNDNHYFGYSTPWGYFDFNRFHCHFSPRDWQRLINNNWGFRPK RLNFKLFNIQVKEVTTNDGVTTIANNLTSTVQVFSDSEYQLPYVLGSAHQGCLPPFPADVFM IPQYGYLTLNNGSQAVGRSSFYCLEYFPSQMLRTGNNFTFSYTFEDVPFHSSYAHSQSLDRL MNPLIDQYLYYLNRTQNQSGSAQNKDLLFSRGSPAGMSVQPKNWLPGPCYRQQRVSKTKTDN NNSNFTWTGASKYNLNGRESIINPGTAMASHKDDKDKFFPMSGVMIFGKESAGASNTALDNV MITDEEEIKATNPVATERFGTVAVNLQSSSTDPATGDVHVMGALPGMVWQDRDVYLQGPIWA KIPHTDGHFHPSPLMGGFGLKHPPPQILIKNTPVPANPPAEFSATKFASFITQYSTGQVSVE IEWELQKENSKRWNPEVQYTSNYAKSANVDFTVDNNGLYTEPRPIGTRYLTRPL Example AAV6.2 VP1 capsid protein (SEQ ID NO: 41) Suitably, the variant may be at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identical to SEQ ID NO: 41. Suitably, the AAV6.2 VP2 and VP3 capsid proteins may be N-terminal truncations of SEQ ID NO: 41, or N-terminal truncations of a variant which is at least 90% identical, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identical to SEQ ID NO: 41. AAV5 serotype The AAV vector particle may comprise an AAV5 capsid protein. Suitably, the AAV vector particle may be encapsidated by AAV5 capsid proteins. The AAV vector particle may comprise an AAV5 VP1 capsid protein, an AAV5 VP2 capsid protein, and / or an AAV5 VP3 capsid protein. Suitably, the AAV vector particle may be encapsidated by AAV5 VP1 capsid proteins, AAV5 VP2 capsid proteins, and / or AAV5 VP3 capsid proteins. Suitably, the AAV vector particle may be encapsidated by AAV5 VP1, VP2, and VP3 capsid proteins. Suitably, the AAV5 VP1 capsid protein may comprise or consist of the amino acid sequence shown as SEQ ID NO: 42, or a variant which is at least 90% identical to SEQ ID NO: 42. MSFVDHPPDWLEEVGEGLREFLGLEAGPPKPKPNQQHQDQARGLVLPGYNYLGPGNGLDRGE PVNRADEVAREHDISYNEQLEAGDNPYLKYNHADAEFQEKLADDTSFGGNLGKAVFQAKKRV LEPFGLVEEGAKTAPTGKRIDDHFPKRKKARTEEDSKPSTSSDAEAGPSGSQQLQIPAQPAS SLGADTMSAGGGGPLGDNNQGADGVGNASGDWHCDSTWMGDRVVTKSTRTWVLPSYNNHQYR EIKSGSVDGSNANAYFGYSTPWGYFDFNRFHSHWSPRDWQRLINNYWGFRPRSLRVKIFNIQ VKEVTVQDSTTTIANNLTSTVQVFTDDDYQLPYVVGNGTEGCLPAFPPQVFTLPQYGYATLN RDNTENPTERSSFFCLEYFPSKMLRTGNNFEFTYNFEEVPFHSSFAPSQNLFKLANPLVDQY LYRFVSTNNTGGVQFNKNLAGRYANTYKNWFPGPMGRTQGWNLGSGVNRASVSAFATTNRME LEGASYQVPPQPNGMTNNLQGSNTYALENTMIFNSQPANPGTTATYLEGNMLITSESETQPV NRVAYNVGGQMATNNQSSTTAPATGTYNLQEIVPGSVWMERDVYLQGPIWAKIPETGAHFHP SPAMGGFGLKHPPPMMLIKNTPVPGNITSFSDVPVSSFITQYSTGQVTVEMEWELKKENSKR WNPEIQYTNNYNDPQFVDFAPDSTGEYRTTRPIGTRYLTRPL Example AAV5 VP1 capsid protein (SEQ ID NO: 42) Suitably, the variant may be at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identical to SEQ ID NO: 42. Suitably, the AAV5 VP2 and VP3 capsid proteins may be N-terminal truncations of SEQ ID NO: 42, or N-terminal truncations of a variant which is at least 90% identical, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identical to SEQ ID NO: 42. Variants, derivatives, homologues and fragments In addition to the specific proteins and nucleotides mentioned herein, the invention also encompasses variants, derivatives, homologues and fragments thereof. In the context of the invention, a “variant” of any given sequence is a sequence in which the specific sequence of residues (whether amino acid or nucleic acid residues) has been modified in such a manner that the polypeptide or polynucleotide in question retains at least one or all of its endogenous functions. A variant sequence can be obtained by addition, deletion, substitution, modification, replacement and / or variation of at least one residue present in the given sequence. The term “derivative” as used herein in relation to proteins or polypeptides of the invention includes any substitution of, variation of, modification of, replacement of, deletion of and / or addition of one (or more) amino acid residues from or to the sequence, providing that the resultant protein or polypeptide retains at least one or all of its endogenous functions. Typically, amino acid substitutions may be made, for example from 1, 2 or 3, to 10 or 20 substitutions, provided that the modified sequence retains the required activity or ability. Amino acid substitutions may include the use of non-naturally occurring analogues. Polypeptides used in the invention may also have deletions, insertions or substitutions of amino acid residues which produce a silent change and result in a functionally equivalent protein. Deliberate amino acid substitutions may be made on the basis of similarity in polarity, charge, solubility, hydrophobicity, hydrophilicity and / or the amphipathic nature of the residues as long as the endogenous function is retained. For example, negatively charged amino acids include aspartic acid and glutamic acid; positively charged amino acids include lysine and arginine; and amino acids with uncharged polar head groups having similar hydrophilicity values include asparagine, glutamine, serine, threonine and tyrosine. Conservative substitutions may be made, for example according to the table below. Amino acids in the same block in the second column and preferably in the same line in the third column may be substituted for each other: ALIPHATIC Non-polar G A P I L V Polar - uncharged C S T M N Q Polar - charged D E K R H AROMATIC F W Y The effect of additions, deletions, substitutions, modifications, replacements and / or variations may be predicted using any suitable prediction tool e.g. SIFT (Vaser, R., et al., 2016. Nature protocols, 11(1), pp.1-9), PolyPhen-2 (Adzhubei, I., et al., 2013. Current protocols in human genetics, 76(1), pp.7-20), CADD (Rentzsch, P., et al., 2021. Genome medicine, 13(1), pp.1- 12), REVEL (Ioannidis, N.M., et al., 2016. The American Journal of Human Genetics, 99(4), pp.877-885), MetaLR (Dong, C., et al., 2015. Human molecular genetics, 24(8), pp.2125- 2137), and / or MutationAssessor (Reva, B., et al., 2011. Nucleic acids research, 39(17), pp.e118-e118) or based on clinical data e.g. ClinVar (Landrum, M.J., et al., 2016. Nucleic acids research, 44(D1), pp.D862-D868). Suitable additions, deletions, substitutions, modifications, replacements and / or variations may be considered tolerated, benign, and / or likely benign. In the present context, a variant sequence is taken to include an amino acid sequence which may be at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85% or at least 90% identical, suitably at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identical to the subject sequence. Although a variant can also be considered in terms of similarity (i.e. amino acid residues having similar chemical properties / functions), in the context of the present invention it is preferred to express it in terms of sequence identity. In the present context, a variant sequence is taken to include a nucleotide sequence which may be at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85% or at least 90% identical, suitably at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identical to the subject sequence. Although a variant can also be considered in terms of similarity, in the context of the present invention it is preferred to express it in terms of sequence identity. The term “homologue” as used herein means a variant having a certain similarity with the wild type amino acid sequence or the wild type nucleotide sequence, e.g. having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85% or at least 90% similarity, suitably at least 95%, at least 96%, at least 97%, at least 98% or at least 99% similarity to the subject sequence. Suitably, reference to a sequence which has a percent identity to any one of the SEQ ID NOs detailed herein refers to a sequence which has the stated percent identity over the entire length of the SEQ ID NO referred to. Sequence identity comparisons can be conducted by eye, or more usually, with the aid of readily available sequence comparison programs. These commercially available computer programs can calculate percent identity between two or more sequences. Percent identity may be calculated over contiguous sequences, i.e. one sequence is aligned with the other sequence and each amino acid or nucleotide in one sequence is directly compared with the corresponding amino acid or nucleotide in the other sequence, one residue at a time. This is called an “ungapped” alignment. Typically, such ungapped alignments are performed only over a relatively short number of residues. Although this is a very simple and consistent method, it fails to take into consideration that, for example, in an otherwise identical pair of sequences, one insertion or deletion in the amino acid or nucleotide sequence may cause the following residues or codons to be put out of alignment, thus potentially resulting in a large reduction in percent identity when a global alignment is performed. Consequently, most sequence comparison methods are designed to produce optimal alignments that take into consideration possible insertions and deletions without penalising unduly the overall identity score. This is achieved by inserting “gaps” in the sequence alignment to try to maximise local identity. However, these more complex methods assign “gap penalties” to each gap that occurs in the alignment so that, for the same number of identical amino acids or nucleotides, a sequence alignment with as few gaps as possible, reflecting higher relatedness between the two compared sequences, will achieve a higher score than one with many gaps. “Affine gap costs” are typically used that charge a relatively high cost for the existence of a gap and a smaller penalty for each subsequent residue in the gap. This is the most commonly used gap scoring system. High gap penalties will produce optimised alignments with fewer gaps. Most alignment programs allow the gap penalties to be modified. However, it is preferred to use the default values when using such software for sequence comparisons. For example when using the GCG Wisconsin Bestfit package the default gap penalty for amino acid sequences is -12 for a gap and -4 for each extension. Calculation of maximum percent identity therefore firstly requires the production of an optimal alignment, taking into consideration gap penalties. A suitable computer program for carrying out such an alignment is the GCG Wisconsin Bestfit package (see e.g. Devereux, J., et al., 1984. Nucleic acids research, 12(1), pp.387-395). Examples of other software that can perform sequence comparisons include, but are not limited to, the BLAST package (see e.g. Altschul, S.F., et al., 1990. Journal of molecular biology, 215(3), pp.403-410), BLAST 2 (see e.g. Tatusova, T.A. and Madden, T.L., 1999. FEMS microbiology letters, 174(2), pp.247-250), FASTA (see e.g. Pearson, W.R. and Lipman, D.J., 1988. PNAS, 85(8), pp.2444-2448.), EMBOSS Needle (Madeira, F., et al., 2019. Nucleic acids research, 47(W1), pp.W636-W641) and the GENEWORKS suite of comparison tools. For some applications, it is preferred to use EMBOSS Needle. Although the final percent identity can be measured, the alignment process itself is typically not based on an all-or-nothing pair comparison. Instead, a scaled similarity score matrix is generally used that assigns scores to each pairwise comparison based on chemical similarity or evolutionary distance. An example of such a matrix commonly used is the BLOSUM62 matrix. Once the software has produced an optimal alignment, it is possible to calculate percent sequence identity. The software typically does this as part of the sequence comparison and generates a numerical result. The percent sequence identity may be calculated as the number of identical residues as a percentage of the total residues in the SEQ ID NO referred to. The term “fragment” as used herein refers to a variant sequence that is a portion of a full- length polypeptide or polynucleotide. Fragments are typically selected regions of the polypeptide or polynucleotide that is of interest either functionally or, for example, in an assay. Such variants, derivatives, homologues and fragments may be prepared using standard recombinant DNA techniques such as site-directed mutagenesis. Where insertions are to be made, synthetic DNA encoding the insertion together with 5’ and 3’ flanking regions corresponding to the naturally-occurring sequence either side of the insertion site may be made. The flanking regions will contain convenient restriction sites corresponding to sites in the naturally-occurring sequence so that the sequence may be cut with the appropriate enzyme(s) and the synthetic DNA ligated into the cut. The DNA is then expressed in accordance with the invention to make the encoded protein. These methods are only illustrative of the numerous standard techniques known in the art for manipulation of DNA sequences and other known techniques may also be used. Vectors, kits, and systems In one aspect, the present invention provides a vector encoding the AAV genome of the present invention. The vector may be a transfer vector, as described herein. For example, the vector may be a plasmid and / or the AAV genome may be operably linked to a promoter (e.g. a viral promoter, such as a CMV promoter). In one aspect, the present invention provides a kit or system for producing the AAV vector of the present invention. The kit or system may be a virus packaging kit or system or a AAV production kit or system. As used herein, an “AAV packaging kit or system” may comprise one or more components, and optionally instructions, for packaging the AAV vector of the present invention. As used herein, a “AAV production kit or system” may comprise one or more components, and optionally instructions, for producing the AAV vector of the present invention. The kit or system may comprise a transfer vector encoding the AAV genome of the present invention and optionally one or more helper vectors. The kit or system may further comprise host cells (e.g. packaging cells or producer cells) and / or other reagents (e.g. transfection reagent, culture medium, etc.). The kit or system may further comprise any other suitable components, and optionally instructions for packaging and / or producing the AAV vector of the present invention. In some embodiments, the kit is for production of AAV vector particles and comprises a plasmid encoding the AAV genome of the present invention, and one or more helper plasmids encoding AAV replication and capsid proteins. Cells In one aspect, the present invention provides a cell comprising the polynucleotide or vector of the present invention. The cell may be any cell type known in the prior art. The cell may be an isolated cell. The cell may be a human cell, suitably an isolated human cell. Suitably, the cell may be a kidney cell or glomerular cell, for example a podocyte. Suitably, the cell may be an immortalized kidney cell or glomerular cell, for example an immortalized podocyte. Suitable podocyte cell lines will be well known to those of skill in the art, for example CIHP-1. Methods to generate immortalized podocytes will be well known to those of skill in the art. Suitable methods are described in Ni, L., et al., 2012. Nephrology, 17(6), pp.525-531. Suitably, the cell may be a producer cell. The term “producer cell” includes a cell that produces viral particles, after transient transfection, stable transfection or vector transduction of all the elements necessary to produce the viral particles or any cell engineered to stably comprise the elements necessary to produce the viral particles. In some embodiments, the producer cell is an AAV producer cell. Suitable producer cells will be known to those of skill in the art (see e.g. Martin, J., et al.2013. Human gene therapy methods, 24(4), pp.253-269) and may include HEK293, COS-1, COS-7, CV-1, HeLa, CHO, and A549 cell lines. In some embodiments, the producer cell is a HEK293 cell, or a derivative thereof (e.g. a HEK293T cell). Suitably, the cell may be a packaging cell. The term “packaging cell” includes a cell which contains some or all of the elements necessary for packaging a recombinant virus genome. Typically, such packaging cells contain one or more vectors which are capable of expressing viral structural proteins (e.g. AAV rep and cap genes) and / or one or more genes encoding the viral structural proteins have been integrated into the genome of the packaging cell. Cells comprising only some of the elements required for the production of enveloped viral particles are useful as intermediate reagents in the generation of viral particle producer cell lines, through subsequent steps of transient transfection, transduction or stable integration of each additional required element. These intermediate reagents are encompassed by the term “packaging cell”. In some embodiments, the packaging cell is an AAV packaging cell. Suitable packaging cells will be known to those of skill in the art (see e.g. Martin, J., et al.2013. Human gene therapy methods, 24(4), pp.253-269). Pharmaceutical compositions In one aspect, the present invention provides a pharmaceutical composition comprising the polynucleotide, vector, or cell of the present invention. Preferably, the vector is an AAV vector particle. A pharmaceutical composition is a composition that comprises or consists of a therapeutically effective amount of a pharmaceutically active agent i.e. the AAV vector particle. It preferably includes a pharmaceutically acceptable carrier, diluent or excipient (including combinations thereof). By “pharmaceutically acceptable” is included that the formulation is sterile and pyrogen free. The carrier, diluent, and / or excipient must be “acceptable” in the sense of being compatible with the vector and not deleterious to the recipients thereof. Typically, the carriers, diluents, and excipients will be saline or infusion media which will be sterile and pyrogen free; however, other acceptable carriers, diluents, and excipients may be used. Acceptable carriers, diluents, and excipients for therapeutic use are well known in the pharmaceutical art. The choice of pharmaceutical carrier, excipient or diluent can be selected with regard to the intended route of administration and standard pharmaceutical practice. The pharmaceutical compositions may comprise as - or in addition to - the carrier, excipient or diluent any suitable binder(s), lubricant(s), suspending agent(s), coating agent(s) or solubilising agent(s). Examples of pharmaceutically acceptable carriers include, for example, water, salt solutions, alcohol, silicone, waxes, petroleum jelly, vegetable oils, polyethylene glycols, propylene glycol, liposomes, sugars, gelatin, lactose, amylose, magnesium stearate, talc, surfactants, silicic acid, viscous paraffin, perfume oil, fatty acid monoglycerides and diglycerides, petroethral fatty acid esters, hydroxymethyl-cellulose, polyvinylpyrrolidone, and the like. The vector, cell, or pharmaceutical composition according to the present invention may be administered in a manner appropriate for treating and / or preventing the diseases described herein. The quantity and frequency of administration will be determined by such factors as the condition of the subject, and the type and severity of the subject's disease, although appropriate dosages may be determined by clinical trials. The pharmaceutical composition may be formulated accordingly. The vector, cell or pharmaceutical composition according to the present invention may be administered parenterally, for example, intravenously, or by infusion techniques. The polynucleotide, vector, cell or pharmaceutical composition may be administered in the form of a sterile aqueous solution which may contain other substances, for example, enough salts or glucose to make the solution isotonic with blood. The aqueous solution may be suitably buffered (preferably to a pH of from 3 to 9). The pharmaceutical composition may be formulated accordingly. The preparation of suitable parenteral formulations under sterile conditions is readily accomplished by standard pharmaceutical techniques well-known to those skilled in the art. The polynucleotide, vector, cell or pharmaceutical composition according to the present invention may be administered systemically, for example by intravenous injection. The polynucleotide, vector, cell or pharmaceutical composition according to the present invention may be administered locally, for example by targeting administration to the kidney. Suitably, the polynucleotide, vector, cell or pharmaceutical composition may be administered by injection into the renal artery, by intraparenchymal injection, by transparenchymal injection, by renal vein injection, or by ureteral or subcapsular injection. In some embodiments, the polynucleotide, vector, cell or pharmaceutical composition is administered by injection into the renal artery. The pharmaceutical compositions may comprise polynucleotides, vectors or cells of the invention in infusion media, for example sterile isotonic solution. The pharmaceutical composition may be enclosed in ampoules, disposable syringes or multiple dose vials made of glass or plastic. The polynucleotide, vector, cell or pharmaceutical composition may be administered in a single or in multiple doses. Particularly, the polynucleotide, vector, cell or pharmaceutical composition may be administered in a single, one-off dose. The pharmaceutical composition may be formulated accordingly. The polynucleotide, vector, cell or pharmaceutical composition may be administered at varying doses (e.g. measured in vector genomes (vg) per kg). The physician in any event will determine the actual dosage which will be most suitable for any individual subject and it will vary with the age, weight and response of the particular subject. Typically, however, for the AAV vectors of the invention, doses of 1010to 1014vg / kg, or 1011to 1013vg / kg may be administered. The pharmaceutical composition may further comprise one or more other therapeutic agents. The invention further includes the use of kits comprising the polynucleotide, vector, cells and / or pharmaceutical composition of the present invention. Preferably said kits are for use in the methods and used as described herein, e.g., the therapeutic methods as described herein. Preferably, said kits comprise instructions for use of the kit components. Methods for treating and / or preventing disease In one aspect, the present invention provides the polynucleotide, vector, cell or pharmaceutical composition of the invention for use as a medicament. In another aspect, the present invention provides use of the polynucleotide, vector, cell or pharmaceutical composition of the invention in the manufacture of a medicament. In another aspect, the present invention provides a method of administering the polynucleotide, vector, cell or pharmaceutical composition of the invention to a subject in need thereof. Subject The subject may be any suitable subject in need thereof. The subject may be a mammal. In preferred embodiments, the subject is a human. The subject may be an adult, an adolescent, or a child. In some embodiments, the subject is a child. In some embodiments, the subject is aged about 16 years or younger. In some embodiments, the subject is aged about 12 years or younger. In some embodiments, the subject is aged about 6 months or older. In some embodiments, the subject is aged about 1 years or older. The subject may have or may be at risk of nephrotic syndrome. The subject may have one or more mutations in NPHS2, which encodes podocin, or a mutation which disrupts the normal expression of NPHS2, for example in the promoter or regulatory regions upstream of NPHS2. In some embodiments, the subject has one or more mutations in NPHS2 or the NPHS2 promoter. In some embodiments, the subject has one or more mutations in NPHS2. There are over 126 such mutations reported to date, but the most common mutation is R138Q, which causes mislocalisation of podocin to the endoplasmic reticulum. Other relevant mutations are described in e.g. Caridi, G., et al., 2005. Pediatric research, 57(7), pp.54-61; and Weber, S., et al., 2004. Kidney international, 66(2), pp.571-579; and Bouchireb, K., et al., 2014. Human mutation, 35(2), pp.178-186. Examples of known mutations in NPHS2 are provided in the table below: Nucleotide change Amino Acid change c.104_126dupGCCGCGGGCGCCAGGAGGCTGGG p.Pro43Alafs*64 c.1150T>C p.*384Glnext*7 c.156delG p.T53Pfs*46 c.167A>G p.Glu56Gly c.1A>T p.M1? c.259G>T p.Glu87* c.264_265delGC p.Pro89Argfs*13 c.353C>T p.Pro118Leu c.377delA p.Lys126Argfs*9 c.378+1_378+2delinsTG p.(?) c.378+1G>A splice c.378+1GT>TG splice c.378+5G>A splice c.379-1G>C splice c.379-2A>C splice c.385C>T p.Gln129* c.388G>A p.Glu130Lys c.397-398delAG p.Arg133Serfs*33 c.397delA p.Arg133Glufs*2 c.412C>T p.Arg138* c.413G>A p.Arg138Gln c.416T>G p.Leu139Arg c.419delG p.Gly140Aspfs*41 c.42delG p.Arg15Glufs*84 c.451+3A>T splice c.467delT p.Leu156Cysfs*25 c.467dupT p.Leu156Phefs*11 c.479A>G p.Asp160Gly c.486C>A p.Tyr162* c.502C>T p.Arg168Cys c.503G>A p.Arg168His c.506T>C p.Leu169Pro c.538G>A p.Val180Met c.593A>C p.Glu198Ala c.596dupA p.Asn199Lysfs*14 c.59C>T p.Pro20Leu c.643C>T p.Gln215* c.705_713del9 p.L236del c.705_713delTCTAGAGAG p.Leu236_Arg238del c.714G>T p.Arg238Ser c.779T>A p.Val260Glu c.790G>T p.Glu264* c.800A>T p.D267V c.826_833dupCACTCACT p.Ala279Thrfs*17 c.841G>A p.Glu281Lys c.851C>T p.Ala284Val c.855_856delAA p.Arg286Thrfs*17 c.856delA p.Arg286Aspfs*7 c.862G>A p.Ala288Thr c.868G>A p.Val290Met c.871C>T p.Arg291Trp c.877A>T p.Ile293Phe c.883G>A p.Ala295Thr c.890C>T p.Ala297Val c.898G>C p.Ala300Pro c.916A>T p.R306W c.926C>T p.Ala309Val c.928G>A p.Glu310Lys c.934C>G p.Leu312Val c.946C>T p.Pro316Ser c.948delT p.Ala317Leufs*31 c.961delC p.Leu321Phefs*27 c.965G>C p.Arg322Pro c.979C>T p.Leu327Phe c.983A>G p.Gln328Arg c.1032delT p.Phe344Leufs*4 Exon 2 del p.(?) In preferred embodiments, the mutation may be p.Arg138Gln, also known as R138Q. R138Q is the most common podocin mutation in children with SRNS in Caucasian populations. The mutation causes endoplasmic reticulum retention of podocin, which prevents it from reaching the slit diaphragm and interacting with other important slit diaphragm proteins to form a functional filtration barrier. As the NPHS2 mutations are all affecting the same gene any combination of these mutations could be prevented and / or treated by the present invention. In other words, the subject may have a p.Arg138Gln mutation and may also have one or more other mutations (e.g. one or more mutations identified above). Nephrotic syndrome In one aspect, the present invention provides the polynucleotide, vector, cell or pharmaceutical composition of the invention for use in treating and / or preventing nephrotic syndrome. In another aspect, the present invention provides use of the polynucleotide, vector, cell or pharmaceutical composition of the invention in the manufacture of a medicament for treating and / or preventing nephrotic syndrome. In another aspect, the present invention provides a method of treating and / or preventing nephrotic syndrome, the method comprising administering the polynucleotide, vector, cell or pharmaceutical composition of the invention to a subject in need thereof. Nephrotic syndrome may be characterised by proteinuria (>3.5 g per 1.73 m2body surface area per day in adults), hypoalbuminemia, hyperlipidaemia, and edema (see e.g. Orth, S.R. and Ritz, E., 1998. New England Journal of Medicine, 338(17), pp.1202-1211; Hull, R.P. and Goldsmith, D.J., 2008. Bmj, 336(7654), pp.1185-1189; and Eddy, A.A. and Symons, J.M., 2003. The lancet, 362(9384), pp.629-639). Treatment of nephrotic syndrome may result in amelioration of one or more symptom of nephrotic syndrome, such as proteinuria, hypoalbuminemia, hyperlipidaemia, and edema. In some embodiments, the nephrotic syndrome is steroid-resistant nephrotic syndrome (SRNS). In some embodiments, the nephrotic syndrome is steroid-resistant nephrotic syndrome type 2. Steroid-resistant nephrotic syndrome type 2 (OMIM #600995) is an autosomal recessive disorder characterized clinically by childhood onset of proteinuria, hypoalbuminemia, hyperlipidemia, and edema. Kidney biopsies show nonspecific histologic changes such as minimal change, focal segmental glomerulosclerosis (FSGS), and diffuse mesangial proliferation. The disorder is resistant to steroid treatment and progresses to end- stage renal failure in the first or second decades. Steroid-resistant nephrotic syndrome type 2 can be caused by homozygous or compound heterozygous mutation in the gene encoding podocin on chromosome 1q25. In some embodiments, the nephrotic syndrome is genetic nephrotic syndrome. In some embodiments, the nephrotic syndrome is caused by one or more mutations in NPHS2, or in the promoter or regulatory regions upstream of NPHS2. In some embodiments, the nephrotic syndrome is caused by one or more mutations in NPHS2. In some embodiments, the nephrotic syndrome is caused by a p.Arg138Gln mutation. In some embodiments, the nephrotic syndrome is genetic SRNS (also known as familial idiopathic SRNS or hereditary steroid-resistant nephrotic syndrome). In some embodiments, the nephrotic syndrome is SRNS caused by one or more mutations in NPHS2, or in the promoter or regulatory regions upstream of NPHS2. In some embodiments, the nephrotic syndrome is SRNS caused by one or more mutations in NPHS2. In some embodiments, the nephrotic syndrome is SRNS caused by a p.Arg138Gln mutation. In some embodiments, the nephrotic syndrome is congenital nephrotic syndrome. Congenital nephrotic syndrome is characterised by nephrotic-range proteinuria, hypoalbuminaemia and oedema, which manifest in utero or during the first 3 months of life. Children with congenital nephrotic syndrome typically develop end-stage renal disease between ages 2 and 8, although with treatment, some may not have kidney failure until adolescence or early adulthood. In some embodiments, kidney failure in the subject is prevented. AAV vector administration In preferred embodiments, an AAV vector is administered to the subject. In more preferred embodiments, the AAV vector is an AAV vector particle. The AAV vector may be administered in any suitable dosage (e.g. measured in vector genomes (vg) or vg per kg). The dosage may be determined by such factors as the condition of the subject, age of the subject, weight of the subject, and the type and severity of the subject's disease, and appropriate dosages may be determined by a physician. The AAV vector may be formulated accordingly. Suitably, the AAV vector is administered in a dose of about 1x106vg / kg or more, about 1x107vg / kg or more, about 1x108vg / kg or more, about 1x109vg / kg or more, about 1x1010vg / kg or more, about 1x1011vg / kg or more, or about 1x1012vg / kg or more. Suitably, the AAV vector is administered in a dose of about 1x1014vg / kg or less or about 1x1013vg / kg or less. Suitably, the AAV vector is administered in a dose of from about 1x106vg / kg to about 1x1014vg / kg. Suitably, the AAV vector is administered in a dose of from about 1x106vg / kg to about 1x1013vg / kg. In some embodiments, the AAV vector is administered in a dose of from about 1x109vg / kg to about 1x1012vg / kg. Suitably, the AAV vector is administered in a dose of about 1x108vg or more, about 1x109vg or more, about 1x1010vg or more, about 1x1011vg or more, about 1x1012vg or more, about 1x1013vg or more, or about 1x1014vg or more. Suitably, the AAV vector is administered in a dose of about 1x1015vg or less or about 1x1014vg or less. Suitably, the AAV vector is administered in a dose of from about 1x108vg to about 1x1015vg. Suitably, the AAV vector is administered in a dose of from about 1x108vg to about 5x1014vg. In some embodiments, the AAV vector is administered in a dose of from about 1x1011vg to about 1x1014vg. The AAV vector may be administered in the form of an AAV vector formulation. As used herein, an “AAV vector formulation” may refer to a composition that comprises or consists of a therapeutically effective amount of a AAV vector. It preferably includes a pharmaceutically acceptable carrier, diluent or excipient (including combinations thereof). By “pharmaceutically acceptable” is included that the formulation is sterile and pyrogen free. The carrier, diluent, and / or excipient must be “acceptable” in the sense of being compatible with the AAV vector and not deleterious to the recipients thereof. Typically, the carriers, diluents, and excipients will be saline or infusion media which will be sterile and pyrogen free, however, other acceptable carriers, diluents, and excipients may be used. The AAV vector may be administered in the form of a sterile aqueous solution which may contain other substances, for example, enough salts or glucose to make the solution isotonic with blood. The aqueous solution may be suitably buffered (preferably to a pH of from 3 to 9). The preparation of suitable parenteral formulations under sterile conditions is readily accomplished by standard pharmaceutical techniques well-known to those skilled in the art. Suitably, the AAV vector formulation comprises an isotonic buffer (e.g. at about pH 7.4). The AAV vector may be delivered by any suitable route of administration. In some embodiments, the AAV vector is administered by injection into the renal artery, by intraparenchymal injection, by transparenchymal injection, by renal vein injection, or by ureteral or subcapsular injection. In some embodiments, the AAV vector is administered by renal artery injection. The practice of the present invention will employ, unless otherwise indicated, conventional techniques of chemistry, biochemistry, molecular biology, microbiology and immunology, which are within the capabilities of a person of ordinary skill in the art. Such techniques are explained in the literature. See, for example: Skoog, D.A., et al. (2013) Fundamentals of Analytical Chemistry, 9th edition, Cengage learning; Walker J.M. (2009) The Protein Protocols Handbook, 3rd edition, Springer Nature; Green, M.R. and Sambrook, J. (2012) Molecular Cloning: A Laboratory Manual, 4th Edition, Cold Spring Harbor Laboratory Press; Ausubel, F.M., et al. (2003) Current Protocols in Molecular Biology, John Wiley & Sons; Hill, A. J. (2013) DNA Sequencing Protocols, Humana Press; Nielsen, B.S. and Jones, J. (2021) In Situ Hybridization Protocols, Springer US; Herdewijn, P. (2010) Oligonucleotide Synthesis: Methods and Applications, Humana Press; and Luo, Y. (2019) CRISPR Gene Editing: Methods and Protocols, Springer New York. Each of these general texts is herein incorporated by reference. EXAMPLES The invention will now be further described by way of examples, which are meant to serve to assist one of ordinary skill in the art in carrying out the invention and are not intended in any way to limit the scope of the invention. Example 1 – Luciferase expression in HEK 293T cells using various kidney-specific promoters in the presence or absence of rabbit beta globin (RBG) intron I A number of constructs were designed and generated encoding a reporter gene (Luc-GFP) under the control of the following kidney-specific promoters: a full-length NPHS1 promoter (NPHS1(FL)), a minimal NPHS1 promoter (NPHS1(265)), a full-length NPHS2 promoter (NPHS2(FL)), and a minimal NPHS2 promoter (NPHS2(628)). To investigate whether the inclusion of a spliceosomal intron can increase the expression of a reporter gene when coupled with a kidney-specific promoter, a fragment of a rabbit-beta globin intron I variant lacking the 5’ splice donor site (RBG) was inserted between the kidney- specific promoter and the luciferase gene. The constructs tested are shown in Figure 1A and include: ^ NPHS1(FL)-Luc-GFP ^ NPHS1(FL)-RBG-Luc-GFP ^ NPHS1(265)-Luc-GFP ^ NPHS1(265)-RBG-Luc-GFP ^ NPHS2(628)-Luc-GFP ^ NPHS2(628)-RBG-Luc-GFP ^ NPHS2(FL)-Luc-GFP ^ NPHS2(FL)-RBG-Luc-GFP The results of the luciferase assays are shown in Figure 1B. Non-transfected cells demonstrate no luciferase activity, as expected. Cells transfected with kidney-specific promoters, in the absence of RBG, demonstrate luciferase expression, with similar expression levels observed using different promoters. Cells transfected with plasmids incorporating the RBG intron demonstrate increased expression of luciferase, relative to the corresponding plasmids lacking the RBG intron. Thus, inclusion of the RBG intron increases the expression of luciferase in HEK293T cells when coupled with kidney-specific promoters. Materials and methods The following sequences were used in the constructs tested: NPHS(FL) = SEQ ID NO: 1 RBG = SEQ ID NO: 7 NPHS1(265) ggccctggggtcacggaggctggggaggcaccgaggaacgcgcctggcatgtgctgaca ggggattttatgctccaggagcaagacagagagagatactcacagggaagaggggaaga (SEQ ID NO: 43) ggaaaacgagaaagggaggagagtaacggaaagagataaaaaagaaaagcaggtggcag agacacacagagagggacccagagaaagccagacagacgcaggtggctggcagcgggcg ctgtgggggtcacagtagggggacctgtg NPHS2(FL) gccctcctatttagtctctctgccacctacaaattgagaaagtcaaatttagtaagtcc ttatagtttccagctctaaaacaacaggatttgtaacatcatgtagtgccaatcaattc (SEQ ID NO: 44) cagcctttccattaaataatccaaatgaatcagtattcatgcattcacttattcatatg gatataatacttcaaaacactaactgggaataagtgtaatactttagaaagccttgcac tctttcataatctttcaccttggaaacataaaagtaaacagctttaattgatcctccct ttcttctagtaacccagttcccacagatgtcagtttcttaacaaatccaaacaaggagt aaagtattgagagtttcagaatgtgtgcatatcatattttcagcaaagggatgagcaac actttcaattaaaaaggaatctaaaagaaaacagcagcatccttgtaaaagtagatgag gacagccagctggacttagctgctaactcagcactcccttccccaactcctccaccttc cagccatgctgcattgacctttttatcatggaatggtatgcagcttctctgattttgtc attgtcactcataatcccagcagacttgtgttataagcagctgcttatattgctgttat gtatagatatagaaatgtaacttgtcagtggtcaaagaagccaaggaaactgagcaaag gtgactgagaacaagtgctcagcatgggctccaacacccagtagggccttttctcattg atttttctcctacaaggaatttctctcttattgaaagacagtacagtttggggaatatc atttgaccagatatcctgctccattcttggaatgaaaaacaggtgcaattttagtataa gagtctagctagggatgcggatgaaattaatttataacaggaccaggctgaggaaaaac accaataaatgctacaaatagtttgtcactttttctaacagggaaatctctaaaggatg ataaagatgctagctgtgtttaatagcaaatgttaatttgggggaatatgaaataatca tgatatctttctctctttgagccaaacgcagctttggaatttttctcactgtagtgttg taggcagaaactatcaactgaggcaggcccttgcgaggaaatatttatcctccttagcc catgcaatgatcaggtttagacagtaaaaaatctatttaagtgactggattgctcatct tttatttactttactcccagtggcctaacctggaacatatagaagaaagtagtggaatg gtttttccagacgcacttcagttacttcaggtcctcagtgtttaataaggttttgggag agaaaaaaagctattgctgtgtgaattcaataaatatttaaaaaatttaaaaaatcagt gagcattatttctgccatcatgtgatctgaactatctgagtagtatcataaatcttggg tgatgggttaccttgaccaacctccctttcagtaagaaacaaattattaacagaaagtg aaagagaaataaacctattcaatgtttcaagtccctcagaagagggtgaggcagctccc cagttcgttgctagatccagcctggccaatgaaccctgaaaaagcccaactcctgcttt catcatggaagcacgggacaaagtgtctcttcctaaaaacagaagttagaccagacccc ttcctgcctatgattcttcaagaagcattgcatcatcaacatcaggcataagcattaat aaagaccctaaataataacagagacgaaacacatcgcaaagagagttttcttttatccc ctttaaaatgtaaatactcccaggaggaatcagccaacatcattaggggttaatgcata tgtagaataactagggccaggatataaaataagaaatacgtagggaggagagaaaggca tccttgagacgactccaagaaggaaagttggggatgaggcgaaatttctgattttacct taaagtgaccctaattcgatgaccttttgtggtttttttcttttttcttttttacttgg ccctgcccaagcaggacctaaaaacaaacagacaaaaaaggttactaacaactgttcct ctccacgaaaatctgcagtaaaaggtaaaagatgtattcgttttgaagagaaaccagag cttgcgatgagcttctgtatctccgtcagccctctagcatgacattaggaaccctccag gagatgagtcttcacagcccgggttggcacctgcagacacgcacttttcaacgcccgca ccctgcccggggccggctctcccacccaggcctctctctgcttcagcgccgccccggcc gtgggagtcggcgggcgcagtccacagctccaccaagacacagctgtcggggttccggg tgcgccccgcccgcggccccggtgtcccgcccctcgccctcagcccccacccgatggtc tttagggtcccccgggcacgccacgcggacccgcagcgactccacagggactgcgctcc cgtgcccctagcgctcccgcgctgctgctccagccgcccggcagctctgaccatg NPHS2(628) ccaagaaggaaagttggggatgaggcgaaatttctgattttaccttaaagtgaccctaa ttcgatgaccttttgtggtttttttcttttttcttttttacttggccctgcccaagcag (SEQ ID NO: 45) gacctaaaaacaaacagacaaaaaaggttactaacaactgttcctctccacgaaaatct gcagtaaaaggtaaaagatgtattcgttttgaagagaaaccagagcttgcgatgagctt ctgtatctccgtcagccctctagcatgacattaggaaccctccaggagatgagtcttca cagcccgggttggcacctgcagacacgcacttttcaacgcccgcaccctgcccggggcc ggctctcccacccaggcctctctctgcttcagcgccgccccggccgtgggagtcggcgg gcgcagtccacagctccaccaagacacagctgtcggggttccgggtgcgccccgcccgc ggccccggtgtcccgcccctcgccctcagcccccacccgatggtctttagggtcccccg ggcacgccacgcggacccgcagcgactccacagggactgcgctcccgtgcccctagcgc tcccgcgctgctgctccagccgcccggcagctctgacc Luc-GFP atggaagacgccaaaaacataaagaaaggcccggcgccattctatccgctagaggatgg aaccgctggagagcaactgcataaggctatgaagagatacgccctggttcctggaacaa (SEQ ID NO: 46) ttgcttttacagatgcacatatcgaggtgaacatcacgtacgcggaatacttcgaaatg tccgttcggttggcagaagctatgaaacgatatgggctgaatacaaatcacagaatcgt cgtatgcagtgaaaactctcttcaattctttatgccggtgttgggcgcgttatttatcg gagttgcagttgcgcccgcgaacgacatttataatgaacgtgaattgctcaacagtatg aacatttcgcagcctaccgtagtgtttgtttccaaaaaggggttgcaaaaaattttgaa cgtgcaaaaaaaattaccaataatccagaaaattattatcatggattctaaaacggatt accagggatttcagtcgatgtacacgttcgtcacatctcatctacctcccggttttaat gaatacgattttgtaccagagtcctttgatcgtgacaaaacaattgcactgataatgaa ctcctctggatctactgggttacctaagggtgtggcccttccgcatagaactgcctgcg tcagattctcgcatgccagagatcctatttttggcaatcaaatcattccggatactgcg attttaagtgttgttccattccatcacggttttggaatgtttactacactcggatattt gatatgtggatttcgagtcgtcttaatgtatagatttgaagaagagctgtttttacgat cccttcaggattacaaaattcaaagtgcgttgctagtaccaaccctattttcattcttc gccaaaagcactctgattgacaaatacgatttatctaatttacacgaaattgcttctgg gggcgcacctctttcgaaagaagtcggggaagcggttgcaaaacgcttccatcttccag ggatacgacaaggatatgggctcactgagactacatcagctattctgattacacccgag ggggatgataaaccgggcgcggtcggtaaagttgttccattttttgaagcgaaggttgt ggatctggataccgggaaaacgctgggcgttaatcagagaggcgaattatgtgtcagag gacctatgattatgtccggttatgtaaacaatccggaagcgaccaacgccttgattgac aaggatggatggctacattctggagacatagcttactgggacgaagacgaacacttctt catagttgaccgcttgaagtctttaattaaatacaaaggataccaggtggcccccgctg aattggagtcgatattgttacaacaccccaacatcttcgacgcgggcgtggcaggtctt cccgacgatgacgccggtgaacttcccgccgccgttgttgttttggagcacggaaagac gatgacggaaaaagagatcgtggattacgtcgccagtcaagtaacaaccgcgaaaaagt tgcgcggaggagttgtgtttgtggacgaagtaccgaaaggtcttaccggaaaactcgac gcaagaaaaatcagagagatcctcataaaggccaagaagggcggaaagtccaaattggg aagcggagctactaacttcagcctgctgaagcaggctggcgacgtggaggagaaccctg gacctatgatggtgagcaagggcgaggagctgttcaccggggtggtgcccatcctggtc gagctggacggcgacgtaaacggccacaagttcagcgtgtccggcgagggcgagggcga tgccacctacggcaagctgaccctgaagttcatctgcaccaccggcaagctgcccgtgc cctggcccaccctcgtgaccaccctgacctacggcgtgcagtgcttcagccgctacccc gaccacatgaagcagcacgacttcttcaagtccgccatgcccgaaggctacgtccagga gcgcaccatcttcttcaaggacgacggcaactacaagacccgcgccgaggtgaagttcg agggcgacaccctggtgaaccgcatcgagctgaagggcatcgacttcaaggaggacggc aacatcctggggcacaagctggagtacaactacaacagccacaacgtctatatcatggc cgacaagcagaagaacggcatcaaggtgaacttcaagatccgccacaacatcgaggacg gcagcgtgcagctcgccgaccactaccagcagaacacccccatcggcgacggccccgtg ctgctgcccgacaaccactacctgagcacccagtccgccctgagcaaagaccccaacga gaagcgcgatcacatggtcctgctggagttcgtgaccgccgccgggatcactctcggca tggacgagctgtacaag Day 1 - HEK293T cells were seeded at a density of 1e6 cells per well of a 6-well plate in a total volume of 2mls. Cells were cultured in DMEM supplemented with 10% FBS. Day 2 - Cells were transfected with plasmid DNA. For this, 2ug DNA was added to a final volume of 300ul DMEM. Separately, 6ul PEI was added to 294ul DMEM.300ul of PEI / DMEM mix was added to the 2ug DNA in DMEM and mixed by pipetting. This was incubated for 15 minutes at room temperature.300ul was then added to a well of the 6-well plate seeded 24 hours prior. Day 3 – Media from transfected cells was replaced with fresh media. Day 4 – Luciferase assay was performed 48 hours following transfection. Briefly, cells were washed once with PBS, followed by adding 1ml of trypsin, and removing the trypsin after covering the cells. Cells were incubated at 37 degrees for 5 minutes. Cells were then resuspended in 1ml of DMEM supplemented with 10% FBS to neutralise the trypsin.100ul of this suspension was added to a V-bottom 96-well plate (FACS plate) and centrifuged at 1000g for 2 minutes. Supernatant was discarded. Cells were re-suspended in 200ul of PBS and centrifuged again to wash the cells. Cells were then lysed and analysed using the Pierce™ Firefly Luciferase Glow Assay Kit (Cat no.16176) as per manufacturer’s instructions. Example 2 – Podocin expression in podocytes and rescue of detachment in diseased podocytes using a nephrin promoter in the presence or absence of rabbit beta globin (RBG) intron I A number of AAV genomes were designed and generated encoding either a reporter gene (GFP) or podocin under the control of a full-length human NPHS1 promoter (hNPHS1(FL)). To investigate whether the inclusion of a spliceosomal intron can increase the expression of the podocin gene when coupled with a kidney-specific promoter, a fragment of a rabbit-beta globin intron I variant lacking the 5’ splice donor site (RBG) was inserted between the kidney- specific promoter and the podocin gene. The AAV genomes tested are shown in Figure 2A and include: ^ GFP: hNPHS1(FL)-GFP ^ C1: hNPHS1(FL)-podocin-F1 Ori ^ #5: hNPHS1(FL)-podocin ^ #10: hNPHS1(FL)-RBG-podocin Cells were transduced with AAV particles, encapsidating the AAV genomes (see Figures 2B- 2E). Figure 2B shows the expression of podocin in healthy podocytes transduced at 1e5 vg / cell. Figure 2C shows the expression of podocin in R138Q patient podocytes transduced at 1e5 vg / cell. Figure 2D shows the expression of podocin in patient podocytes transduced at 5e4 vg / cell. Figure 2E shows the expression of podocin in patient podocytes transduced at 1e4 vg / cell. This data demonstrates the expression of podocin upon transduction of human podocytes with AAV particles encapsidating a podocin gene driven by the full length nephrin promoter in the presence or absence of RBG intron I. In the presence of RBG intron I, expression is increased by approximately 4-5 fold in both healthy and R138Q patient podocytes. The increased podocin expression observed in the presence of RBG intron I may be due to increased mRNA stability. At a multiplicity of infection of 1e5 vg / cell, podocyte loss (caused by detachment of the podocytes from the plate) is observed in cells from a patient with a R138Q podocin mutation in either non-transduced cells (NT) or cells transduced with GFP (GFP). Rescue of podocyte loss is observed when cells are transduced with an AAV genome comprising the RBG intron (#10) (see Figure 2F). #10 rescues podocyte detachment at a lower multiplicity of infection than #5 (which lacks the RBG intron) and is 4-fold more effective than #5 at 5e4 vg / cell (see Figures 2G and 2H). Thus, inclusion of the RBG intron increases the expression of podocin in podocytes when coupled with a kidney-specific promoter and improves the rescue of podocyte loss in a podocyte detachment assay. Materials and methods The following sequences were used in the constructs tested: hNPHS1(FL) = SEQ ID NO: 1 RBG = SEQ ID NO: 7 Podocin = SEQ ID NO: 9 GFP atggtgagcaagggcgaggagctgttcaccggggtggtgcccatcctggtcgagctgga cggcgacgtaaacggccacaagttcagcgtgtccggcgagggcgagggcgatgccacct (SEQ ID NO: 47) acggcaagctgaccctgaagttcatctgcaccaccggcaagctgcccgtgccctggccc accctcgtgaccaccctgacctacggcgtgcagtgcttcagccgctaccccgaccacat gaagcagcacgacttcttcaagtccgccatgcccgaaggctacgtccaggagcgcacca tcttcttcaaggacgacggcaactacaagacccgcgccgaggtgaagttcgagggcgac accctggtgaaccgcatcgagctgaagggcatcgacttcaaggaggacggcaacatcct ggggcacaagctggagtacaactacaacagccacaacgtctatatcatggccgacaagc agaagaacggcatcaaggtgaacttcaagatccgccacaacatcgaggacggcagcgtg cagctcgccgaccactaccagcagaacacccccatcggcgacggccccgtgctgctgcc cgacaaccactacctgagcacccagtccgccctgagcaaagaccccaacgagaagcgcg atcacatggtcctgctggagttcgtgaccgccgccgggatcactctcggcatggacgag ctgtacaagtaa AAV Production: 70-80% confluent Lenti-X 293T Human Embryonic Kidney cells grown in DMEM supplemented with 10% FBS were triple transfected with pHelper, pAAV Rep-Cap (LK03) and one of the three ITR-expression plasmids containing the Full Length (FL) Nephrin promoter, with or without RBG intron driving Podocin expression. Transfection was carried out on a 150mm culture dish in the presence of polyethylenimine (PEI). Media was changed to DMEM with FBS the following day after transfection. On Day 4 post-transfection, media and cells were collected and processed separately. PEG was added to filtered supernatants to precipitate viral particles which were subsequently centrifuged at 1500g for 20 minutes. Cell pellets were resuspended in TD buffer and frozen at -80 degrees, followed by thawing at 37 degrees and vortexed. Freeze-thaw cycles were repeated 5 times. Pellets from the PEG treated supernatant were then added to the lysed cells and Benzonase and Sodium deoxycholate was further added and incubated at 37 degrees for 30 minutes. Samples were then centrifuged, and the supernatant filtered and subsequently purified via iodixanol gradient ultracentrifugation. AAV QC: AAV samples were titred via qPCR to determine the number of viral genomes per ml of viral supernatant. SDS-PAGE analysis was performed on samples to determine purity. Alkaline gel electrophoresis was used to demonstrate incorporation of full transgene cassettes into the viral particles. AAV Transduction: Immortalised Human Podocyte cells were seeded into wells of a 6-well plate at a density of 9e4 cells / well and allowed to adhere overnight at 33°C. The following day cells were transduced at multiplicity of infection (MOI) of 1e5 viral genome per cell in 1ml of complete media (RPMI supplemented with 10% FBS and 1% Insulin-Transferrin-Selenium (ITS)). 4 hours later each well was topped up with 1ml of complete media and cells were thermoswitched to 37°C to initiate differentiation. Media was changed every 2-3 days. Gene Expression analysis: After 10 days cells were harvested by scraping and pelleted. Cell pellet were then lysed using 1x Cell Extraction buffer provided with Podocin ELISA kit (Abcam, cat: Ab245708). Total protein quantification was assessed using Pierce BCA kit (Thermo Scientific, cat: 23227).0.25ug and 1.25ug of Total protein (of constructs with RBG and without RBG respectively) was used to quantify Podocin level using Podocin ELISA kit. Podocin expression was then calculated in picogram per ug of total protein. Rescue of detachment assay: Conditionally immortalised podocyte cells are seeded into t25 tissue culture plates at a density of 7.8e5 cells / plate in 2ml of RPMI-1640 media (Sigma R8758). Cells are cultured at 33 degrees for 4 hours to allow time to sufficiently attach to plates. Cells are then transduced at chosen multiplicity of infection (MOI) in 2ml of RPMI-1640 media. Cells are transferred back to incubator for a further 4 hours, before medium is topped up to 4ml and cells are transferred to 37-degree incubator to begin differentiation. Media on cells is changed 3 times weekly. On day 7 of differentiation imaging is performed by taking (per flask) 10 bright-field images at 10x magnification (from random areas spanning the entire plate) (using Leica DMIL LED Fluo microscope). The same process is repeated on day 10 of differentiation. ImageJ is used to quantify the percentage of empty space between cells in each image, which is averaged from 10 images for each plate at each timepoint. The percentage change in cell coverage between day 7 and day 10 gives rise to the “Percentage Loss” metric presented in figures. Example 3 – Expression of podocin in podocytes and rescue of detachment in diseased podocytes using a CMV promoter Example 2 was repeated with an AAV genome encoding podocin under the control of a CMV promoter (see Figure 3D), to investigate whether very high expression levels can affect rescue of detachment in diseased podocytes. Healthy podocytes and R138Q patient podocytes were transduced with AAV encapsidating GFP under the control of a full-length human NPHS1 promoter (GFP), podocin under the control of a full-length human NPHS1 promoter (C1), or podocin under the control of a CMV promoter (CMV-podocin). A higher level of podocin expression was observed with transduction of CMV-podocin in comparison to transduction with C1 in healthy podocytes (see Figure 3A). However, in diseased podocytes, a higher level of podocin expression was observed with transduction of C1 in comparison to transduction with CMV-podocin (see Figure 3B). This may be explained by a higher number of podocytes becoming detached due to cellular stress in response to high levels of podocin expression driven by the CMV promoter, therefore fewer cells are available for the podocin expression assay. Expression of podocin under the CMV promoter in R138Q podocytes does not lead to rescue of podocyte loss (see Figure 3C). The rescue of detachment assay appears to demonstrate that CMV-driven podocin expression in R138Q mutant podocytes induces podocyte loss in the assay and podocyte detachment is not rescued by very high expression of podocin. Thus, inclusion of an intron may be advantageous over replacing the kidney-specific promoter with a stronger promoter, (e.g. a CMV promoter). For example, in contrast to the CMV promoter, inclusion of the RBG intron provides the correct level of podocin expression in podocytes and improves the rescue of podocyte loss in a podocyte detachment assay. Example 4 – Transfection of HEK cells to measure gene expression in the presence or absence of the RBG intron I regulatory element HEK cells were transfected with the following constructs, to determine the increase in expression due to the RBG intron I regulatory element: ^ NPHS1(265)-RBG-reporter1 vs NPHS1(265)-reporter1 ^ NPHS1(265)-RBG-reporter2 vs NPHS1(265)-reporter2 ^ NPHS1(265)-RBG-reporter3 vs NPHS1(265)-reporter3 Western blot results are shown in Figure 4. Band intensity indicates that the addition of a RBG intron I regulatory element to a kidney specific promoter improved expression of all three reporter transgenes relative to just the kidney-specific promoter alone following transfection in HEK cells. Materials and methods The following sequences were used in the constructs tested: NPHS1(265) = SEQ ID NO: 43 RBG = SEQ ID NO: 7 Reporter1, reporter2 and reporter3 = codon-optimised reporter transgenes Day 1: HEK AD293 cells were seeded at a density of 2e5 cells per well in a 6-well plate in 2mL DMEM media supplemented with 10% FBS. Day 2: Cells were transfected with plasmid DNA. For this, DNA was added to a final volume of 175 µL plain DMEM. Separately, 4 µL PEI was added to 171 µL plain DMEM. 175 µL PEI / DMEM mix was added to the DNA mix and incubated at room temperature for 15 minutes. After this time, 300 µL of this mix, containing 2 µg DNA is added dropwise to a well of the 6-well plate seeded the day before. Day 3: Media from transfected cells is removed and cells are gently washed with 1x PBS. Then 1.2 mL serum-free DMEM is added. Day 6: Media was removed and transferred to 1.5 mL Protein LoBind tubes (#Eppendorf), then centrifuged at 13,000 rpm for 10 minutes at 4°C. The clarified supernatant was then aliquotted and stored at –80°C. Cell supernatants were prepared for SDS-PAGE in a total volume of 20 µL with 4x Laemmli Buffer and 1M DTT. Protein denaturation was then conducted by boiling the samples for 5 minutes at 95°C. Each sample (15 µL / well) was loaded into 4-15% MiniProtean TGX pre-cast polyacrylamide gels and run in 1x Tris / Glycine SDS buffer at 130V for 40 minutes. Pageruler Plus Prestained Protein Ladder (8 µL) was loaded in parallel for reference. After briefly rinsing with water, the gels were then transferred to the nitrocellulose membrane of iBlot 2 regular transfer stacks (Invitrogen). Dry transfer was conducted with the iBlot Gel Transfer Device (Invitrogen) using P0 program for 7 minutes. Then, the membranes were removed, rinsed in diH2O, and incubated in blocking buffer (5% milk in TBS-T) for 2 hours at room temperature. The membranes were then incubated overnight at 4°C with blocking buffer containing an anti-HA antibody (#C29F4, Cell Signalling) at 1:1000 dilution. The following day, the membranes were washed in TBS-T 3 times for 10 minutes at room temperature, before incubating with an anti-rabbit HRP antibody (#AP307P, Sigma-Aldrich) diluted 1:20,000 for 1 hour at room temperature. After 3 additional washes in TBS-T, the membranes were developed for 5 minutes in SuperSignal West Atto ECL reagent before imaging on chemiluminescent settings at the Amersham ImageQuant 800. Example 5 – AAV transduction of human podocytes to measure gene expression in the presence or absence of the RBG intron I element Human podocytes were transduced with the following LK03 AAV vectors, to determine the increase in expression due to the RBG intron I regulatory element: ^ LK03-NPHS1(265)-RBG-reporter1 vs LK03-NPHS1(265)-reporter1 ^ LK03-NPHS1(265)-RBG-reporter3 vs LK03-NPHS1(265)-reporter3 Western blot results and protein quantification are shown in Figure 5. Band intensity and protein levels indicate that the addition of a RBG intron I regulatory element to a kidney- specific promoter improved expression of both reporter transgenes relative to just the kidney specific-promoter alone following transduction of human podocytes with LK03 AAV vectors. Materials and methods The following sequences were used in the constructs tested: LK03 VP1 = SEQ ID NO: 36 NPHS1(265) = SEQ ID NO: 43 RBG = SEQ ID NO: 7 Reporter1 and reporter3 = codon-optimised reporter transgenes LK03 AAV vectors containing the relevant transgenes were produced by suspension cell vector production and purified by ultracentrifugation. Titres were measured by qPCR using primers targeting the WPRE sequence. Day 1: Human Podocytes were seeded into a 12-well plate at a density of 3.5e4 cells per well in 1mL complete medium, containing RPMI-1640 medium supplemented with 10% FBS. Cells were then cultured at 33°C. Day 2: Transduction mixes were prepared in sterile 1.5 mL Protein LoBind tubes (#Eppendorf) in a total volume of 550 µL complete medium. Culture medium was removed from the cells and 500 µL of each transduction mix is added to each well (MOI of 1e5 vg / cell). Cells were then incubated at 33°C for 4 hours. After this, the culture medium was topped up to 1 mL per well with complete medium and the cells were placed at 37°C to differentiate into mature podocytes. Day 3: The culture medium was removed, and the cells were gently washed 3 times with 1x PBS. Then 600 µL serum-free RPMI-1640 was added to each well and cells placed back at 37°C. Day 6: The cell supernatant was collected, centrifuged in 1.5mL Protein LoBind tubes (#Eppendorf) at 13,000 rpm for 10 minutes at 4°C and stored in aliquots at –80°C. Western blotting was performed as described for Example 4. An ELISA kit was used to quantify the levels of protein in the cell supernatant. Example 6 – In vivo study to measure gene expression in the presence or absence of the RBG intron I regulatory element Mice were intravenously injected with AAV9-NPHS1(265)-reporter3 or AAV9-NPHS1(265)- RBG-reporter3, to determine the increase in expression due to the RBG intron I regulatory element. The gene expression was determined by RT-qPCR and amount of vector genomes by qPCR (see Figure 6). Figure 6A shows a significant increase in gene expression induced by the treatment of wild-type mice with an AAV vector containing the RBG intron I regulatory element (NPHS1(265).RBG.reporter3), compared to a vector without this regulatory element (NPHS1(265).reporter3), in presence of similar amount of vector genomes (see Figure 6B). Figure 6C confirms higher expression levels in the kidney in the presence of the RBG intron I regulatory element. The RBG intron I regulatory element drives increased gene and protein expression in the kidney of mice intravenously injected with AAV9 vectors. Materials and methods The following sequences were used in the constructs tested: AAV9 VP1 = SEQ ID NO: 37 NPHS1(265) = SEQ ID NO: 43 RBG = SEQ ID NO: 7 Reporter3 = codon-optimised reporter transgene Mouse study Adult wild-type 129 / sv female mice received intravenous injection in the tail vein of 1.5e12 vg AAV9-265-reporter3 or AAV9-265-RBG-reporter3 and were culled at 2, 5 or 9 weeks post- dosing (n=4 per group per timepoint). The health and welfare of the mice was monitored and recorded using a welfare scoring sheet; this was performed on Day 0, 20 minutes following the procedure, on Day 1, and then weekly until the end of the study. Any animal exhibiting mild adverse effects was closely monitored by increasing the number of clinical checks; any animal exhibiting moderate clinical signs was culled. DNA, RNA and protein were isolated from tissues to assess vector biodistribution, gene and protein expression. qPCR and RT-qPCR All-Prep DNA / RNA Mini kit (Qiagen) was used to extract genomic DNA (gDNA) and RNA samples from 2 separate kidney tissue pieces per mouse (each around 25 mg in weight), which were then combined into a single sample after the elution steps. A qPCR infectivity assay targeting the WPRE sequence of the vector and using Taqman Universal Master Mix (Applied Biosystems), was performed on the gDNA samples to detect viral DNA in the tissues. Samples were run at 50 ng and 100 ng to assess linearity. A standard curve was generated by using a gene block serial dilution containing the target WPRE sequence and by plotting its log(concentration) on X axis and the relative cycle threshold (Ct) mean in Y axis; range covered: 5 x 107 to 5 copies. Quantification of absolute copies per well was determined by interpolating the samples’ average Ct values. Results were displayed as copies per µg of gDNA. 2.5 µg of RNA for each sample was retrotranscribed to cDNA by using the SuperScript™ IV VILO™ kit (Invitrogen). In parallel, no-RT controls were generated for each sample and run on the RT-qPCR assay along with the RT samples. A RT-qPCR assay, targeting the WPRE sequence and using Taqman Universal Master Mix (Applied Biosystems), was performed on the cDNA. Samples were run at 2 different dilutions (1:20 and 1:40, as final dilutions) to check linearity. A standard curve was generated by using a gene block’s serial dilution containing the target WPRE sequence and by plotting its log(concentration) on the X axis and the relative Ct mean on the Y axis; range covered: 5 x 107 to 5 copies. Quantification of absolute copies per well was determined by interpolating the samples’ average Ct values. Results were displayed as RNA copies per µg of RNA. Protein extraction and ELISA Tissue protein lysates were prepared in T-PER tissue protein extraction reagent (Life technologies, #78510) supplemented by protease inhibitor cocktail (Sigma P8340, 1:100). One 7 mm stainless steel bead (Qiagen, #69990) was added to each tube for tissue homogenization. Samples were then spun at maximum speed for 10 minutes. The supernatant was transferred to a new Protein LoBind tubes (Eppendorf), and stored at -80°C until the protein quantification was performed by Bicinchoninic acid (BCA) assay following the manufacturer’s instructions. An ELISA was developed in-house to detect protein in mouse kidney tissue lysates. A Nunc Maxisorp clear bottom 96-well plate (ThermoFisher) was coated with polyclonal antiserum overnight in 1x coating buffer (BUT030B Biorad) at 4°C. On day 2, 1L wash buffer (1x PBS, 0.05% Tween) and 50 mL assay buffer (1x PBS-T, 1% BSA) were prepared. Standards (Comptech purified FH in assay buffer), blank (assay buffer) and samples were prepared at RT by diluting in assay buffer. Standards were prepared by a serial dilution of 1:2 from 50 to 0.78 ng / mL. Matrix recovery and spike-in analyses were performed to determine the final dilution of 1:10 as the optimal sample working dilution. All standards and samples were run in duplicates. The coated plate was washed 3 times with 300 µL wash buffer, tapped dry and blocked with 200 µL assay buffer per well, sealed and incubated for 1 hour at RT. The assay buffer was then discarded from the plate, tapped dry and 50 µL standard samples were loaded per well. The plate was sealed and incubated for 1 hour at RT. The plate was then washed 3 times with 300 µL wash buffer, tapped dry and incubated with 50 µL of primary antibody (1µg / mL; OX23 Biorad) per well, at RT for 1 hour. Primary antibody was biotinylated in-house using EZ LinkTM Sulfo-NHS-LC-Biotin, No-WeighTM Format Biotinylation kit and ZebaTM Spin Desalting Columns, 7kDa MWCO (ThermoFisher). The plate was washed 3 times with 300 µL wash buffer, tapped dry on absorbent paper, and incubated for 1 hour at RT with 1:1000 Extravidin HRP antibody. The plate was washed 3 times with 300 µL wash buffer, dried, and incubated in 50 µL TMB solution for 30 minutes at RT, protected from light.50 µL Stop solution (0.5M Sulphuric acid) was added and gently tapped to mix. The plate reader was used immediately to measure at 450 nm absorbance. Graphpad software was used to perform analysis, using 4PL curve for standard curve interpolation. Results were displayed as concentrations normalized to their BCA values and subtracted from the average non-treated lysate for background subtraction.

Claims

CLAIMS 1. A polynucleotide comprising: a 5’ ITR; a kidney-specific promoter; a regulatory element comprising a spliceosomal intron or a fragment thereof comprising a branch point sequence, a polypyrimidine tract, and a 3’ splice acceptor site; a protein-coding sequence encoding podocin; and a 3’ ITR.

2. The polynucleotide according to claim 1, wherein the kidney-specific promoter is a NPHS1 promoter.

3. The polynucleotide according to claim 1 or 2, wherein the kidney-specific promoter comprises or consists of a nucleotide sequence having 80% or more, 85% or more, 90% or more, 91% or more, 92% or more, 93% or more, 94% or more, 95% or more, 96% or more, 97% or more, 98% or more, 99% or more, or 100% sequence identity to SEQ ID NO:

1.

4. The polynucleotide according to any preceding claim, wherein the kidney-specific promoter consists of the nucleotide sequence of SEQ ID NO:

1.

5. The polynucleotide according to any preceding claim, wherein the spliceosomal intron is the rabbit beta globin intron I or a variant thereof having at least 80% sequence identity thereto.

6. The polynucleotide according to any preceding claim, wherein the regulatory element does not comprise a 5’ splice donor site.

7. The polynucleotide according to any preceding claim, wherein the regulatory element comprises or consists of a nucleotide sequence having 80% or more, 85% or more, 90% or more, 91% or more, 92% or more, 93% or more, 94% or more, 95% or more, 96% or more, 97% or more, 98% or more, 99% or more, or 100% sequence identity to SEQ ID NO:

7.

8. The polynucleotide according to any preceding claim, wherein the regulatory element consists of the nucleotide sequence of SEQ ID NO:

7.

9. The polynucleotide according to any preceding claim, wherein the protein-coding sequence encodes an amino acid sequence having 80% or more, 85% or more, 90% or more, 91% or more, 92% or more, 93% or more, 94% or more, 95% or more, 96% or more, 97% or more, 98% or more, 99% or more, or 100% sequence identity to SEQ ID NO:

8.

10. The polynucleotide according to any preceding claim, wherein the protein-coding sequence encodes the amino acid sequence of SEQ ID NO: 8.

11. The polynucleotide according to any preceding claim, wherein the protein-coding sequence comprises or consists of a nucleotide sequence having 80% or more, 85% or more, 90% or more, 91% or more, 92% or more, 93% or more, 94% or more, 95% or more, 96% or more, 97% or more, 98% or more, 99% or more, or 100% sequence identity to SEQ ID NO:

9.

12. The polynucleotide according to any preceding claim, wherein the protein-coding sequence consists of the nucleotide sequence of SEQ ID NO:

9.

13. The polynucleotide according to any preceding claim, wherein the 5’ ITR is an AAV25’ ITR and / or the 3’ ITR is an AAV23’ ITR.

14. The polynucleotide according to any preceding claim, wherein the 5’ ITR comprises or consists of a nucleotide sequence having 80% or more, 85% or more, 90% or more, 91% or more, 92% or more, 93% or more, 94% or more, 95% or more, 96% or more, 97% or more, 98% or more, 99% or more, or 100% sequence identity to SEQ ID NO: 52, preferably wherein the 5’ ITR consists of the nucleotide sequence of SEQ ID NO:

52.

15. The polynucleotide according to any preceding claim, wherein the 3’ ITR comprises or consists of a nucleotide sequence having 80% or more, 85% or more, 90% or more, 91% or more, 92% or more, 93% or more, 94% or more, 95% or more, 96% or more, 97% or more, 98% or more, 99% or more, or 100% sequence identity to SEQ ID NO: 53, preferably wherein the 3’ ITR consists of the nucleotide sequence of SEQ ID NO:

53.

16. The polynucleotide according to any preceding claim, wherein the polynucleotide further comprises a WPRE.

17. The polynucleotide according to claim 16, wherein the WPRE comprises or consists of a nucleotide sequence having 80% or more, 85% or more, 90% or more, 91% or more, 92% or more, 93% or more, 94% or more, 95% or more, 96% or more, 97% or more, 98% or more, 99% or more, or 100% sequence identity to SEQ ID NO: 10, preferably wherein the WPRE consists of the nucleotide sequence of SEQ ID NO:

10.

18. The polynucleotide according to any preceding claim, wherein the polynucleotide further comprises a polyadenylation sequence.

19. The polynucleotide according to claim 18, wherein the polyadenylation sequence is a bovine growth hormone (bGH) polyadenylation sequence.

20. The polynucleotide according to claim 18 or 19, wherein the polyadenylation sequence comprises or consists of a nucleotide sequence having 80% or more, 85% or more, 90% ormore, 91% or more, 92% or more, 93% or more, 94% or more, 95% or more, 96% or more, 97% or more, 98% or more, 99% or more, or 100% sequence identity to SEQ ID NO: 11, preferably wherein the polyadenylation sequence consists of the nucleotide sequence of SEQ ID NO:

11.

21. The polynucleotide according to any preceding claim, wherein the polynucleotide comprises from 5’ to 3’: a 5’ ITR; a kidney-specific promoter; a regulatory element comprising a spliceosomal intron or a fragment thereof comprising a branch point sequence, a polypyrimidine tract, and a 3’ splice acceptor site; a protein-coding sequence encoding podocin; optionally, a WPRE; optionally, a polyadenylation sequence; and a 3’ ITR.

22. The polynucleotide according to any preceding claim, wherein the polynucleotide comprises: a 5’ ITR; a kidney-specific promoter consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 1; a regulatory element consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 7; a podocin coding sequence consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 9; optionally, a Woodchuck Hepatitis Virus Post-transcriptional Regulatory Element (WPRE) consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 10; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 11; and a 3’ ITR.

23. The polynucleotide according to any preceding claim, wherein the polynucleotide comprises: a 5’ ITR; a kidney-specific promoter consisting of a nucleotide sequence having at least 85% sequence identity to SEQ ID NO: 1; a regulatory element consisting of a nucleotide sequence having at least 85% sequence identity to SEQ ID NO: 7; a podocin coding sequence consisting of a nucleotide sequence having at least 85% sequence identity to SEQ ID NO: 9; optionally, a Woodchuck Hepatitis Virus Post-transcriptional Regulatory Element (WPRE) consisting of a nucleotide sequence having at least 85% sequence identity to SEQ ID NO: 10; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 85% sequence identity to SEQ ID NO: 11; and a 3’ ITR.

24. The polynucleotide according to any preceding claim, wherein the polynucleotide comprises: a 5’ ITR; a kidney-specific promoter consisting of a nucleotide sequence having at least 90% sequence identity to SEQ ID NO: 1; a regulatory element consisting of a nucleotide sequence having at least 90% sequence identity to SEQ ID NO: 7; a podocin coding sequence consisting of a nucleotide sequence having at least 90% sequence identity to SEQ ID NO: 9; optionally, a Woodchuck Hepatitis Virus Post-transcriptional Regulatory Element (WPRE) consisting of a nucleotide sequence having at least 90% sequence identity to SEQ ID NO: 10;optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 90% sequence identity to SEQ ID NO: 11; and a 3’ ITR.

25. The polynucleotide according to any preceding claim, wherein the polynucleotide comprises: a 5’ ITR; a kidney-specific promoter consisting of a nucleotide sequence having at least 95% sequence identity to SEQ ID NO: 1; a regulatory element consisting of a nucleotide sequence having at least 95% sequence identity to SEQ ID NO: 7; a podocin coding sequence consisting of a nucleotide sequence having at least 95% sequence identity to SEQ ID NO: 9; optionally, a Woodchuck Hepatitis Virus Post-transcriptional Regulatory Element (WPRE) consisting of a nucleotide sequence having at least 95% sequence identity to SEQ ID NO: 10; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 95% sequence identity to SEQ ID NO: 11; and a 3’ ITR.

26. The polynucleotide according to any preceding claim, wherein the polynucleotide comprises: a 5’ ITR; a kidney-specific promoter consisting of a nucleotide sequence having at least 99% sequence identity to SEQ ID NO: 1; a regulatory element consisting of a nucleotide sequence having at least 99% sequence identity to SEQ ID NO: 7; a podocin coding sequence consisting of a nucleotide sequence having at least 99% sequence identity to SEQ ID NO: 9; optionally, a Woodchuck Hepatitis Virus Post-transcriptional Regulatory Element (WPRE) consisting of a nucleotide sequence having at least 99% sequence identity to SEQ ID NO: 10; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 99% sequence identity to SEQ ID NO: 11; and a 3’ ITR.

27. The polynucleotide according to any preceding claim, wherein the polynucleotide comprises: a 5’ ITR; a kidney-specific promoter consisting of the nucleotide sequence of SEQ ID NO: 1; a regulatory element consisting of the nucleotide sequence having of SEQ ID NO: 7; a podocin coding sequence consisting of the nucleotide sequence of SEQ ID NO: 9; optionally, a Woodchuck Hepatitis Virus Post-transcriptional Regulatory Element (WPRE) consisting of the nucleotide sequence of SEQ ID NO: 10; optionally, a polyadenylation sequence consisting of the nucleotide sequence of SEQ ID NO: 11; and a 3’ ITR.

28. The polynucleotide according to any preceding claim, wherein the polynucleotide comprises a nucleotide sequence having at least 90% sequence identity to SEQ ID NO: 34 or 54.

29. The polynucleotide according to any preceding claim, wherein the polynucleotide comprises a nucleotide sequence having at least 95% sequence identity to SEQ ID NO: 34 or 54.

30. The polynucleotide according to any preceding claim, wherein the polynucleotide comprises a nucleotide sequence having at least 99% sequence identity to SEQ ID NO: 34 or 54.

31. The polynucleotide according to any preceding claim, wherein the polynucleotide comprises the nucleotide sequence of SEQ ID NO: 34 or 54.

32. An AAV vector comprising the polynucleotide according to any of claims 1 to 31.

33. An AAV vector particle comprising the polynucleotide according to any of claims 1 to 31.

34. The AAV vector particle according to claim 33, wherein the AAV vector particle is encapsidated by LK03, AAV3B, AAV9, ShH10, AAV-DJ, AAV2, AAV6.2, or AAV5 capsid proteins.

35. The AAV vector particle according to claim 33 or 34, wherein the AAV vector particle is encapsidated by LK03 capsid proteins.

36. The AAV vector particle according to any of claims 33 to 35, wherein the AAV vector particle is encapsidated by capsid proteins having 95% or more, 96% or more, 97% or more, 98% or more, 99% or more, or 100% sequence identity to SEQ ID NO:

36.

37. The AAV vector particle according to any of claims 33 to 36, wherein the AAV vector particle is encapsidated by capsid proteins consisting of the amino acid sequence of SEQ ID NO:

36.

38. A pharmaceutical composition comprising the polynucleotide according to any of claims 1 to 31, the AAV vector according to claim 32, or the AAV vector particle according to any of claims 33 to 37, and a pharmaceutically acceptable carrier, diluent and / or excipient.

39. A polynucleotide according to any of claims 1 to 31, an AAV vector according to claim 32, an AAV vector particle according to any of claims 33 to 37, or a pharmaceutical composition according to claim 38, for use as a medicament.

40. Use of a polynucleotide according to any of claims 1 to 31, an AAV vector according to claim 32, an AAV vector particle according to any of claims 33 to 37, or a pharmaceutical composition according to claim 38, for the manufacture of a medicament.

41. A polynucleotide according to any of claims 1 to 31, an AAV vector according to claim 32, an AAV vector particle according to any of claims 33 to 37, or a pharmaceutical composition according to claim 38, for use in treating nephrotic syndrome.

42. The polynucleotide, AAV vector, AAV vector particle, or pharmaceutical composition for use according to claim 41, wherein the nephrotic syndrome is steroid-resistant nephrotic syndrome (SRNS).

43. The polynucleotide, AAV vector, AAV vector particle, or pharmaceutical composition for use according to claim 41 or 42, wherein the nephrotic syndrome is genetic steroid-resistant nephrotic syndrome (SRNS).

44. The polynucleotide, AAV vector, AAV vector particle, or pharmaceutical composition for use according to any of claims 41 to 43, wherein the nephrotic syndrome is caused by one or more mutations in NPHS2, or in the promoter or regulatory regions upstream of NPHS2.

45. The polynucleotide, AAV vector, AAV vector particle, or pharmaceutical composition for use according to any of claims 41 to 44, wherein the AAV vector, AAV vector particle, or pharmaceutical composition is administered by renal artery injection, by intraparenchymal injection, by transparenchymal injection, by renal vein injection, by ureteral injection, or by subcapsular injection.

46. Use of a polynucleotide according to any of claims 1 to 31, an AAV vector according to claim 32, an AAV vector particle according to any of claims 33 to 37, or a pharmaceutical composition according to claim 38, for the manufacture of a medicament for treating nephrotic syndrome.

47. The use according to claim 46, wherein the nephrotic syndrome is steroid-resistant nephrotic syndrome (SRNS).

48. The use according to claim 46 or 47, wherein the nephrotic syndrome is genetic steroid- resistant nephrotic syndrome (SRNS).

49. The use according to any of claims 46 to 48, wherein the nephrotic syndrome is caused by one or more mutations in NPHS2, or in the promoter or regulatory regions upstream of NPHS2.

50. The use according to any of claims 46 to 49, wherein the AAV vector, AAV vector particle, or pharmaceutical composition is administered by renal artery injection, by intraparenchymal injection, by transparenchymal injection, by renal vein injection, by ureteral injection, or by subcapsular injection.

51. A method of treating nephrotic syndrome, the method comprising administering a polynucleotide according to any of claims 1 to 31, an AAV vector according to claim 32, anAAV vector particle according to any of claims 33 to 37, or a pharmaceutical composition according to claim 38, to a subject in need thereof.

52. The method according to claim 51, wherein the nephrotic syndrome is steroid-resistant nephrotic syndrome (SRNS).

53. The method according to claim 51 or 52, wherein the nephrotic syndrome is genetic steroid-resistant nephrotic syndrome (SRNS).

54. The method according to any of claims 51 to 53, wherein the nephrotic syndrome is caused by one or more mutations in NPHS2, or in the promoter or regulatory regions upstream of NPHS2.

55. The method according to any of claims 51 to 54, wherein the AAV vector, AAV vector particle, or pharmaceutical composition is administered by renal artery injection, by intraparenchymal injection, by transparenchymal injection, by renal vein injection, by ureteral injection, or by subcapsular injection.

56. A vector comprising the polynucleotide according to any of claims 1 to 31.

57. The vector according to claim 56, wherein the vector is a plasmid.

58. A kit for production of AAV vector particles comprising a vector according to claim 56 or 57, and one or more helper plasmids encoding AAV replication and capsid proteins.

59. An isolated cell comprising the polynucleotide according to any of claims 1 to 31, the AAV vector according to claim 32, the AAV vector particle according to any of claims 33 to 37, or the vector according to claim 56 or 57.

60. The cell according to claim 59, wherein the cell is a packaging cell.

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