Polynucleotides, AAV vectors, and pharmaceutical compositions for treating complement-mediated kidney diseases

Abstract

The present invention relates to a polynucleotide comprising: a 5' ITR; a kidney-specific promoter; a regulatory element, wherein the regulatory element comprises a super core promoter, or 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 CFI, CFH, or FHL-1; and a 3' ITR.

Description

[0001]POLYNUCLEOTIDES, AAV VECTORS, AND PHARMACEUTICAL COMPOSITIONS FOR TREATING COMPLEMENT-MEDIATED KIDNEY DISEASES FIELD OF THE INVENTION The present invention relates to polynucleotides, AAV vectors, and pharmaceutical compositions for treating complement-mediated kidney diseases. BACKGROUND TO THE INVENTION The kidney is particularly susceptible to damage by chronic, uncontrolled, and excessive activation of the complement cascade. The reasons for this susceptibility are incompletely understood but may be related to the presence of the fenestrae continuously exposing the acellular subendothelial tissues to complement activators, a lower baseline expression of complement regulators, and / or differences in the composition of the glycocalyx. C3G is a rare, complement-mediated kidney disease and includes two overlapping pathologies, dense deposit disease (DDD) and C3 glomerulonephritis. C3G at presentation is clinically indistinguishable from other glomerulonephritides, presenting with non-visible haematuria, proteinuria, hypertension, nephrotic syndrome and renal impairment. Diagnosis is therefore histopathological on renal biopsy, with sole or dominant C3 deposition in the glomeruli. Median age of onset is 23 years, 50% of patients develop end-stage kidney disease by 10 years after diagnosis, and risk of recurrence in a renal transplant is high (see Willows, J., et al., 2020. Clinical Medicine, 20(2), p.156). Dysregulation of complement has also been implicated in IgA Nephropathy (IgAN). IgAN is the most common primary glomerulonephritis in the world. A diagnosis of IgAN is associated with an average reduction in life expectancy of 6–10 years and approximately 40% of IgAN patients older than 30 years age at diagnosis develop end stage renal disease (ESRD) over 20 years. However, development of complement inhibiting drugs is challenging due to the high concentration of complement proteins in the circulation and uncertainty whether abnormal complement in a disease-state is a response to or driver of pathology. Moreover, a major potential side effect of systemic complement inhibiting drugs is infection with encapsulated organisms, and a 1,000-fold increase in life-threatening meningococcal infections has been observed (see Willows, J., et al., 2020. Clinical Medicine, 20(2), p.156) Thus, there is a demand for new therapeutics for treating complement-mediated kidney disorders. SUMMARY OF THE INVENTION The present invention provides an AAV vector encoding a complement inhibitor which demonstrates surprisingly high expression levels in podocytes. Expression of a complement inhibitor in podocytes can prevent and / or treat podocyte-driven complement-mediated disease by down-regulating the complement cascade. In one aspect, the present invention provides a polynucleotide comprising: a 5’ ITR; a kidney- specific promoter; a regulatory element, wherein the regulatory element comprises a super core promoter, or 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 a complement inhibitor; and a 3’ ITR. Any suitable kidney-specific promoter may be used. In some embodiments, the kidney-specific promoter is a podocyte-specific promoter. In some embodiments, the kidney-specific promoter is a NPHS1 promoter. In some embodiments, the kidney-specific promoter is a minimal 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: 2. In some embodiments, the kidney- specific promoter consists of the nucleotide sequence of SEQ ID NO: 2. In some embodiments, the regulatory element comprises or consists of a super core promoter. Any suitable super core promoter may be used. In some embodiments, the super core promoter is the super core promoter 1. 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: 5. In some embodiments, the regulatory element consists of the nucleotide sequence of SEQ ID NO: 5. In some embodiments, the regulatory element comprises or consists of a spliceosomal intron or a fragment thereof comprising a branch point sequence, a polypyrimidine tract, and a 3’ splice acceptor site. Any suitable spliceosomal intron 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: 15. In some embodiments, the regulatory element consists of the nucleotide sequence of SEQ ID NO: 15. Any suitable protein-coding sequence encoding a complement inhibitor may be used. In some embodiments, the protein coding sequence encodes CFI, CFH and / or FHL-1. In some embodiments, the protein coding sequence encodes CFI, CFH, FHL-1, or CFI and FHL-1. In some embodiments, the protein coding sequence encodes CFI. 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: 31. In some embodiments, the protein coding sequence encodes the amino acid sequence of SEQ ID NO: 31. 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: 33. In some embodiments, the protein coding sequence comprises or consists of the nucleotide sequence of SEQ ID NO: 33. 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: 34. In some embodiments, the protein coding sequence comprises or consists of the nucleotide sequence of SEQ ID NO: 34. 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: 35. In some embodiments, the protein coding sequence comprises or consists of the nucleotide sequence of SEQ ID NO: 35. In some embodiments, the protein coding sequence encodes CFH. 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: 36. In some embodiments, the protein coding sequence encodes the amino acid sequence of SEQ ID NO: 36. 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: 37. In some embodiments, the protein coding sequence comprises or consists of the nucleotide sequence of SEQ ID NO: 37. In some embodiments, the protein coding sequence encodes FHL-1. 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: 38. In some embodiments, the protein coding sequence encodes the amino acid sequence of SEQ ID NO: 38. 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: 39. In some embodiments, the protein coding sequence comprises or consists of the nucleotide sequence of SEQ ID NO: 39. In some embodiments, the protein coding sequence encodes CFI and FHL-1. In some embodiments, the nucleotide sequences encoding CFI and FHL-1 are linked by a nucleotide sequence encoding a 2A self-cleaving peptide. In some embodiments, the 2A self-cleaving peptide consists of the amino acid sequence of SEQ ID NO: 44. In some embodiments, the nucleotide encoding a 2A self-cleaving peptide 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: 45. In some embodiments, the nucleotide encoding a 2A self-cleaving peptide consists of the nucleotide sequence of SEQ ID NO: 45. 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: 47. 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: 49. 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: 82. In some embodiments, the 5’ ITR consists of the nucleotide sequence of SEQ ID NO: 82. 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: 83. In some embodiments, the 3’ ITR consists of the nucleotide sequence of SEQ ID NO: 83. 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: 50. In some embodiments, the WPRE consists of the nucleotide sequence of SEQ ID NO: 50. 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: 51. In some embodiments, the polyadenylation sequence consists of the nucleotide sequence of SEQ ID NO: 51. In some embodiments, the polynucleotide comprises from 5’ to 3’: a 5’ ITR; a kidney-specific promoter; a regulatory element, wherein the regulatory element comprises a super core promoter, or 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 a complement inhibitor; optionally, a WPRE; optionally, a polyadenylation sequence; and a 3’ ITR. In another aspect, the present invention provides a polynucleotide comprising: a 5’ ITR; a kidney-specific promoter; a super core promoter; a protein coding sequence encoding CFI; optionally, a Woodchuck Hepatitis Virus Post-transcriptional Regulatory Element (WPRE); optionally, a polyadenylation sequence; and a 3’ ITR. In another aspect, the present invention provides a polynucleotide comprising: a 5’ ITR; a kidney-specific promoter consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 2; a super core promoter consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 5; a CFI coding sequence consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 33; 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: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 51; 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: 52. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 80% identical to SEQ ID NO: 52. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 85% identical to SEQ ID NO: 52. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 90% identical to SEQ ID NO: 52. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 95% identical to SEQ ID NO: 52. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 98% identical to SEQ ID NO: 52. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 99% identical to SEQ ID NO: 52. In some embodiments, the polynucleotide comprises the nucleotide sequence SEQ ID NO: 52. In another aspect, the present invention provides a polynucleotide comprising: a 5’ ITR; a kidney-specific promoter consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 2; a super core promoter consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 5; a CFI coding sequence consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 34; 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: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 51; 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: 53. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 80% identical to SEQ ID NO: 53. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 85% identical to SEQ ID NO: 53. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 90% identical to SEQ ID NO: 53. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 95% identical to SEQ ID NO: 53. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 98% identical to SEQ ID NO: 53. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 99% identical to SEQ ID NO: 53. In some embodiments, the polynucleotide comprises the nucleotide sequence SEQ ID NO: 53. In another aspect, the present invention provides a polynucleotide comprising: a 5’ ITR; a kidney-specific promoter consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 2; a super core promoter consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 5; a CFI coding sequence consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 35; 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: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 51; 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: 54. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 80% identical to SEQ ID NO: 54. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 85% identical to SEQ ID NO: 54. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 90% identical to SEQ ID NO: 54. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 95% identical to SEQ ID NO: 54. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 98% identical to SEQ ID NO: 54. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 99% identical to SEQ ID NO: 54. In some embodiments, the polynucleotide comprises the nucleotide sequence SEQ ID NO: 54. In another aspect, the present invention provides a polynucleotide comprising: a 5’ ITR; a kidney-specific promoter; a super core promoter; a protein coding sequence encoding CFH; optionally, a Woodchuck Hepatitis Virus Post-transcriptional Regulatory Element (WPRE); optionally, a polyadenylation sequence; and a 3’ ITR. In another aspect, the present invention provides a polynucleotide comprising: a 5’ ITR; a kidney-specific promoter consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 2; a super core promoter consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 5; a CFH coding sequence consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 37; 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: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 51; 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: 55. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 80% identical to SEQ ID NO: 55. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 85% identical to SEQ ID NO: 55. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 90% identical to SEQ ID NO: 55. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 95% identical to SEQ ID NO: 55. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 98% identical to SEQ ID NO: 55. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 99% identical to SEQ ID NO: 55. In some embodiments, the polynucleotide comprises the nucleotide sequence SEQ ID NO: 55. In another aspect, the present invention provides a polynucleotide comprising: a 5’ ITR; a kidney-specific promoter; a super core promoter; a protein coding sequence encoding FHL-1; optionally, a Woodchuck Hepatitis Virus Post-transcriptional Regulatory Element (WPRE); optionally, a polyadenylation sequence; and a 3’ ITR. In another aspect, the present invention provides a polynucleotide comprising: a 5’ ITR; a kidney-specific promoter consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 2; a super core promoter consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 5; a FHL-1 coding sequence consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 39; 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: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 51; 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: 56. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 80% identical to SEQ ID NO: 56. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 85% identical to SEQ ID NO: 56. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 90% identical to SEQ ID NO: 56. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 95% identical to SEQ ID NO: 56. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 98% identical to SEQ ID NO: 56. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 99% identical to SEQ ID NO: 56. In some embodiments, the polynucleotide comprises the nucleotide sequence SEQ ID NO: 56. In another aspect, the present invention provides a polynucleotide comprising: a 5’ ITR; a kidney-specific promoter; a super core promoter; a protein coding sequence encoding CFI and FHL-1; optionally, a Woodchuck Hepatitis Virus Post-transcriptional Regulatory Element (WPRE); optionally, a polyadenylation sequence; and a 3’ ITR. In some embodiments, the protein coding sequence encodes from 5’ to 3’: CFI; a 2A self- cleaving peptide; and FHL-1. In another aspect, the present invention provides a polynucleotide comprising: a 5’ ITR; a kidney-specific promoter consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 2; a super core promoter consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 5; a protein coding sequence consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 47; 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: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 51; 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: 57. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 80% identical to SEQ ID NO: 57. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 85% identical to SEQ ID NO: 57. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 90% identical to SEQ ID NO: 57. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 95% identical to SEQ ID NO: 57. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 98% identical to SEQ ID NO: 57. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 99% identical to SEQ ID NO: 57. In some embodiments, the polynucleotide comprises the nucleotide sequence SEQ ID NO: 57. In some embodiments, the protein coding sequence encodes from 5’ to 3’: FHL-1; a 2A self- cleaving peptide; and CFI. In another aspect, the present invention provides a polynucleotide comprising: a 5’ ITR; a kidney-specific promoter consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 2; a super core promoter consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 5; a protein coding sequence consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 49; 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: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 51; 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: 58. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 80% identical to SEQ ID NO: 58. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 85% identical to SEQ ID NO: 58. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 90% identical to SEQ ID NO: 58. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 95% identical to SEQ ID NO: 58. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 98% identical to SEQ ID NO: 58. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 99% identical to SEQ ID NO: 58. In some embodiments, the polynucleotide comprises the nucleotide sequence SEQ ID NO: 58. In another 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 CFI; optionally, a Woodchuck Hepatitis Virus Post- transcriptional Regulatory Element (WPRE); optionally, a polyadenylation sequence; and a 3’ ITR. In another aspect, the present invention provides a polynucleotide comprising: a 5’ ITR; a kidney-specific promoter consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 2; a regulatory element consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 15; a CFI coding sequence consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 33; 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: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 51; 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: 59. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 80% identical to SEQ ID NO: 59. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 85% identical to SEQ ID NO: 59. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 90% identical to SEQ ID NO: 59. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 95% identical to SEQ ID NO: 59. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 98% identical to SEQ ID NO: 59. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 99% identical to SEQ ID NO: 59. In some embodiments, the polynucleotide comprises the nucleotide sequence SEQ ID NO: 59. 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: 84. In some embodiments, the polynucleotide comprises or consists of a nucleotide sequence which is at least 80% identical to SEQ ID NO: 84. In some embodiments, the polynucleotide comprises or consists of a nucleotide sequence which is at least 85% identical to SEQ ID NO: 84. In some embodiments, the polynucleotide comprises or consists of a nucleotide sequence which is at least 90% identical to SEQ ID NO: 84. In some embodiments, the polynucleotide comprises or consists of a nucleotide sequence which is at least 95% identical to SEQ ID NO: 84. In some embodiments, the polynucleotide comprises or consists of a nucleotide sequence which is at least 98% identical to SEQ ID NO: 84. In some embodiments, the polynucleotide comprises or consists of a nucleotide sequence which is at least 99% identical to SEQ ID NO: 84. In some embodiments, the polynucleotide comprises or consists of the nucleotide sequence SEQ ID NO: 84. In another aspect, the present invention provides a polynucleotide comprising: a 5’ ITR; a kidney-specific promoter consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 2; a regulatory element consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 15; a CFI coding sequence consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 34; 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: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 51; 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: 60. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 80% identical to SEQ ID NO: 60. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 85% identical to SEQ ID NO: 60. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 90% identical to SEQ ID NO: 60. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 95% identical to SEQ ID NO: 60. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 98% identical to SEQ ID NO: 60. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 99% identical to SEQ ID NO: 60. In some embodiments, the polynucleotide comprises the nucleotide sequence SEQ ID NO: 60. In another aspect, the present invention provides a polynucleotide comprising: a 5’ ITR; a kidney-specific promoter consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 2; a regulatory element consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 15; a CFI coding sequence consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 35; 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: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 51; 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: 61. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 80% identical to SEQ ID NO: 61. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 85% identical to SEQ ID NO: 61. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 90% identical to SEQ ID NO: 61. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 95% identical to SEQ ID NO: 61. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 98% identical to SEQ ID NO: 61. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 99% identical to SEQ ID NO: 61. In some embodiments, the polynucleotide comprises the nucleotide sequence SEQ ID NO: 61. In another 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 CFH; optionally, a Woodchuck Hepatitis Virus Post- transcriptional Regulatory Element (WPRE); optionally, a polyadenylation sequence; and a 3’ ITR. In another aspect, the present invention provides a polynucleotide comprising: a 5’ ITR; a kidney-specific promoter consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 2; a regulatory element consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 15; a CFH coding sequence consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 37; 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: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 51; 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: 62. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 80% identical to SEQ ID NO: 62. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 85% identical to SEQ ID NO: 62. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 90% identical to SEQ ID NO: 62. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 95% identical to SEQ ID NO: 62. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 98% identical to SEQ ID NO: 62. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 99% identical to SEQ ID NO: 62. In some embodiments, the polynucleotide comprises the nucleotide sequence SEQ ID NO: 62. In another 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 FHL-1; optionally, a Woodchuck Hepatitis Virus Post-transcriptional Regulatory Element (WPRE); optionally, a polyadenylation sequence; and a 3’ ITR. In another aspect, the present invention provides a polynucleotide comprising: a 5’ ITR; a kidney-specific promoter consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 2; a regulatory element consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 15; a FHL-1 coding sequence consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 39; 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: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 51; 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: 63. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 80% identical to SEQ ID NO: 63. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 85% identical to SEQ ID NO: 63. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 90% identical to SEQ ID NO: 63. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 95% identical to SEQ ID NO: 63. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 98% identical to SEQ ID NO: 63. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 99% identical to SEQ ID NO: 63. In some embodiments, the polynucleotide comprises the nucleotide sequence SEQ ID NO: 63. In another 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 CFI and FHL-1; optionally, a Woodchuck Hepatitis Virus Post-transcriptional Regulatory Element (WPRE); optionally, a polyadenylation sequence; and a 3’ ITR. In some embodiments, the protein coding sequence encodes from 5’ to 3’: CFI; a 2A self- cleaving peptide; and FHL-1. In another aspect, the present invention provides a polynucleotide comprising: a 5’ ITR; a kidney-specific promoter consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 2; a regulatory element consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 15; a protein coding sequence consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 47; 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: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 51; 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: 64. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 80% identical to SEQ ID NO: 64. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 85% identical to SEQ ID NO: 64. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 90% identical to SEQ ID NO: 64. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 95% identical to SEQ ID NO: 64. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 98% identical to SEQ ID NO: 64. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 99% identical to SEQ ID NO: 64. In some embodiments, the polynucleotide comprises the nucleotide sequence SEQ ID NO: 64. In some embodiments, the protein coding sequence encodes from 5’ to 3’: FHL-1; a 2A self- cleaving peptide; and CFI. In another aspect, the present invention provides a polynucleotide comprising: a 5’ ITR; a kidney-specific promoter consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 2; a regulatory element consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 15; a protein coding sequence consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 49; 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: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 51; 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: 65. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 80% identical to SEQ ID NO: 65. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 85% identical to SEQ ID NO: 65. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 90% identical to SEQ ID NO: 65. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 95% identical to SEQ ID NO: 65. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 98% identical to SEQ ID NO: 65. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 99% identical to SEQ ID NO: 65. In some embodiments, the polynucleotide comprises the nucleotide sequence SEQ ID NO: 65. In another aspect, the present invention provides a polynucleotide comprising a codon- optimised protein-coding sequence encoding CFI, wherein the protein-coding sequence comprises or consists of a nucleotide sequence having at least 70% sequence identity to SEQ ID NO: 33. In some embodiments, the protein-coding sequence 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: 33. In some embodiments, the protein-coding sequence comprises or consists of the nucleotide sequence of SEQ ID NO: 33. In another aspect, the present invention provides a polynucleotide comprising a codon- optimised protein-coding sequence encoding CFH, wherein the protein-coding sequence comprises or consists of a nucleotide sequence having at least 70% sequence identity to SEQ ID NO: 37. In some embodiments, the protein-coding sequence 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: 37. In some embodiments, the protein-coding sequence comprises or consists of the nucleotide sequence of SEQ ID NO: 37. In another aspect, the present invention provides a polynucleotide comprising a codon- optimised protein-coding sequence encoding FHL-1, wherein the protein-coding sequence comprises or consists of a nucleotide sequence having at least 70% sequence identity to SEQ ID NO: 39. In some embodiments, the protein-coding sequence 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: 39. In some embodiments, the protein-coding sequence comprises or consists of the nucleotide sequence of SEQ ID NO: 39. In another aspect, the present invention provides an AAV vector comprising a polynucleotide of the present invention. In another aspect, the present invention provides an AAV vector particle comprising a 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: 67. In some embodiments, the AAV vector particle is encapsidated by capsid proteins consisting of the amino acid sequence of SEQ ID NO: 67. 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 or preventing a complement-mediated kidney disease. 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 or preventing a complement-mediated kidney disease. In another aspect, the present invention provides a method of treating or preventing a complement-mediated kidney disease, 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. In some embodiments, the complement-mediated kidney disease is IgA nephropathy, membranous nephropathy, or C3 glomerulopathy. In some embodiments, the complement- mediated kidney disease is IgA nephropathy. 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. In some embodiments, 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. In some embodiments, the cell is a packaging cell. DESCRIPTION OF DRAWINGS Figure 1 – Expression of luciferase in HEK 293T cells in the presence or absence of super core promoter 1 (SCP1) (A) Schematic of constructs tested. (B) Luciferase expression in HEK 293T cells by luciferase assay. Figure 2 – 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. Figure 3 – Expression of CFI, FHL1, CFH in HEK AD293 cells in the presence or absence of super core promoter 1 (SCP1) 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). Ladder = Molecular weight markers; NT = non-transfected cells; SCP1.CFI = cells transfected with NPHS1(265)-SCP1-coCFI plasmid; CFI = cells transfected with NPHS1(265)-coCFI plasmid; SCP1.FHL1 = cells transfected with NPHS1(265)-SCP1-coFHL1 plasmid; FHL = cells transfected with NPHS1(265)-coFHL plasmid; SCP1.CFH = cells transfected with NPHS1(265)-SCP1-coCFH plasmid; CFH = cells transfected with NPHS1(265)-coCFH plasmid. Figure 4 – Expression of CFI and FHL1 in human podocytes in the presence or absence of super core promoter 1 (SCP1) Human podocytes were transduced with LK03 AAV vectors at MOI 1e5vg / 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)-SCP1-coFHL1 vs LK03-NPHS1(265)-coFHL1 (n=2 independent biological replicates). (B) Representative immunoblot showing supernatant from non-treated cells (NT) and from podocytes transduced with LK03-NPHS1(265)-SCP1-coCFI vs LK03-NPHS1(265)- coCFI (n=2 independent biological replicates). (C) CFI protein quantified by ELISA in supernatant from non-treated cells (NT) and from podocytes transduced with LK03- NPHS1(265)-SCP1-coCFI vs LK03-NPHS1(265)-coCFI (n=2 independent biological replicates). Ladder = Molecular weight markers; NT = non-transduced cells; SCP1.FHL1 = cells transduced with LK03-NPHS1(265)-SCP1-coFHL1 AAV vector; FHL1 = cells transduced with LK03-NPHS1(265)-coFHL1 AAV vector; SCP1.CFI = cells transduced with LK03- NPHS1(265)-SCP1-coCFI AAV vector; CFI = cells transduced with LK03-NPHS1(265)-coCFI AAV vector. Figure 5 – Expression of CFI, FHL1, CFH 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-CFI vs CFI (n=2 independent biological replicates). (B) Immunoblots showing supernatant from non-treated cells (NT) and from cells transfected with plasmid containing RBG-FHL1 vs FHL1 (n=2 independent biological replicates). (C) Immunoblots showing supernatant from non-treated cells (NT) and from cells transfected with plasmid containing RBG-CFH vs CFH (n=2 independent biological replicates). Ladder = Molecular weight markers; NT = non-transfected cells; RBG.CFI = cells transfected with NPHS1(265)-RBG-coCFI plasmid; CFI = cells transfected with NPHS1(265)-coCFI plasmid; RBG.FHL1 = cells transfected with NPHS1(265)-RBG-coFHL1 plasmid; FHL = cells transfected with NPHS1(265)-coFHL1 plasmid; RBG.CFH = cells transfected with NPHS1(265)-RBG-coCFH plasmid; CFH = cells transfected with NPHS1(265)-coCFH plasmid. Figure 6 – Expression of CFI and FHL1 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-coCFI vs LK03-NPHS1(265)-coCFI, and LK03-NPHS1(265)-RBG-coFHL1 vs LK03-NPHS1(265)-coFHL1 (n=2 independent biological replicates). (B) CFI protein quantified by ELISA in supernatant from non-treated cells (NT) and from podocytes transduced with LK03-NPHS1(265)-RBG-coCFI vs LK03-NPHS1(265)-coCFI (n=2 independent biological replicates). Ladder = Molecular weight markers; NT = non-transduced cells; RGB.CFI = cells transduced with LK03-NPHS1(265)-RGB-coCFI AAV vector; CFI = cells transduced with LK03-NPHS1(265)-coCFI AAV vector; RGB.FHL1 = cells transduced with LK03-NPHS1(265)-RGB-coFHL1 AAV vector; FHL1 = cells transduced with LK03- NPHS1(265)-coFHL1 AAV vector. Figure 7 – Expression of FHL1 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)-coFHL1 or AAV9-NPHS1(265)-RBG-coFHL1 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 FHL1 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 FHL1 protein per µg of total protein and shown as mean ± SEM. Figure 8 – Expression of CFI, FHL1, CFH in HEK AD293 cells 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) or by ELISA. (A) Immunoblots showing supernatant from non-treated cells (NT) and from cells transfected with plasmids containing a codon optimised or wild-type CFI sequence (coCFI and wtCFI, respectively). (B) Immunoblots showing supernatant from non-treated cells (NT) and from cells transfected with plasmids containing a codon optimised or wild-type FHL1 sequence (coFHL1 and wtFHL1, respectively). (C) Immunoblots showing supernatant from non-treated cells (NT) and from cells transfected with plasmids containing a codon optimised or wild-type CFH sequence (coCFH and wtCFH, respectively). (D) CFI protein quantified by ELISA in supernatant from non-treated cells (NT) and from cells transfected with plasmids containing the SCP1 enhancer and a codon optimised or wild-type CFI sequence (SCP1-coFI and SCP1-wtFI, respectively). Data are from n=2 independent biological replicates. (E) CFI protein quantified by ELISA in supernatant from non-treated cells (NT) and from cells transfected with plasmids containing the RBG enhancer and a codon optimised or wild-type CFI sequence (RBG-coFI and RBG-wtFI, respectively). Data are from n=2 independent biological replicates. 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, wherein the regulatory element comprises a super core promoter, and / or 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 a complement inhibitor; and a 3’ ITR. In some embodiments, the polynucleotide comprises from 5’ to 3’: a 5’ ITR; a kidney-specific promoter; a regulatory element, wherein the regulatory element comprises a super core promoter, and / or 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 a complement inhibitor; 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. Kidney-specific promoters The polynucleotide of the present invention comprises a kidney-specific promoter. The kidney- specific promoter may be operably linked to the protein-coding sequence. A “promoter” may refer to 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). A promoter typically comprises a “core” and a “proximal” region. The “core promoter region” may comprise a transcription start site, a RNA polymerase binding sites and a general transcription factor binding site. The “proximal promoter region” may comprise primary regulatory elements and specific transcription factor binding sites which are required, for example, to facilitate effective and controllable transcription. 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 kidney-specific 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. NPHS1 promoter 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. Suitably, the NPHS1 promoter may comprise or consist 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 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identical to 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) The NPHS1 promoter may be a minimal NPHS1 promoter. Suitably, the NPHS1 promoter has a length of about 1.1 kb or less, about 1.0 kb or less, about 0.9 kb or less, about 0.8 kb or less, about 0.7 kb or less, about 0.6 kb or less, about 0.5 kb or less, about 0.4 kb or less, or about 0.3 kb or less. Suitably, the NPHS1 promoter has a length of about 265 bp or more. In some embodiments, the NPHS1 promoter has a length of about 265-1100 bp, 265-1000 bp, 265- 900 bp, 265-800 bp, 265-700 bp, 265-600 bp, 265-500 bp, 265-400 bp, or 265-300 bp. In some embodiments, the kidney-specific promoter comprises or consists of the nucleotide sequence shown as SEQ ID NO: 2, or a variant which is at least 70% identical to SEQ ID NO: 2. 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: 2. In some embodiments, the kidney-specific promoter comprises or consists of the nucleotide sequence shown as SEQ ID NO: 2. In some embodiments, the kidney-specific promoter consists of the nucleotide sequence shown as SEQ ID NO: 2, or a variant which is at least 70% identical to SEQ ID NO: 2. 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: 2. In preferred embodiments, the kidney-specific promoter consists of the nucleotide sequence shown as SEQ ID NO: 2. ggccctggggtcacggaggctggggaggcaccgaggaacgcgcctggcatgtgctgacaggg gattttatgctccaggagcaagacagagagagatactcacagggaagaggggaagaggaaaa cgagaaagggaggagagtaacggaaagagataaaaaagaaaagcaggtggcagagacacaca gagagggacccagagaaagccagacagacgcaggtggctggcagcgggcgctgtgggggtca cagtagggggacctgtg Example minimal NPHS1 promoter (SEQ ID NO: 2) The kidney-specific promoter may comprise or consist of a variant of SEQ ID NO: 2 shown as SEQ ID NO: 3 or SEQ ID NO: 4. ggccctggggtcacggaggctggggaggcaccgaggaacgcgcctggcatgtgctgacaggg aattttatgctccaggagcaagacagagagagacactcacagggaagaggggaagaggaaaa cgagaaagggaggagagtaacggaaagagataaaaaagaaaagcaggtggcagagacacaga gagagggacccagagaaagccagacagacgcaggtggctggcagcgggcgctgtgggggtca cagtagggggacctgtc Example minimal NPHS1 promoter variant (SEQ ID NO: 3) ggccctggggtcacggaggctggggaggcaccgaggaacgcgcctggcatgtgctgacaggg gattttatgctccaggagcaagacagagagagatactcacagggaagaggggaagaggaaaa cgagaaagggaggagagtaacggaaagagataaaaaagaaaagcaggtggcagagacacaga gagagggacccagagaaagccagacagacgcaggtggctggcagcgggcgctgtgggggtca cagtagggggacctgtc Example minimal NPHS1 promoter variant (SEQ ID NO: 4) In some embodiments, the kidney-specific promoter may comprise or consist of the nucleotide sequence shown as SEQ ID NO: 3 or 4, or a variant which is at least 70% identical to SEQ ID NO: 3 or 4. Suitably, the variant may be 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% or at least 99% identical to SEQ ID NO: 3 or 4. Regulatory elements The polynucleotide of the present invention furthers comprises a regulatory element comprising (a) a super core promoter; and / or (b) 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). Super core promoters In some embodiments, the regulatory element comprises or consists of a super core promoter. The “core promoter” is typically 80 nucleotides long, encompassing from -40 to +40 relative to the transcription start site and consists of several functional sub-regions, termed core elements or motifs. A “super core promoter” may refer to a synthetic core promoter which contains a combination of core promoter elements that drive high levels of transcription. For example, a super core promoter may contain a TATA box, an initiator motif (Inr), a motif ten element (MTE) and a downstream promoter element (DPE). Example super core promoters have been described in Juven-Gershon, T., et al., 2006. Nature methods, 3(11), pp.917-922 and Even, D.Y., et al., 2016. PloS one, 11(2), p.e0148918. Suitably, the super core promoter is selected from super core promoter 1 (SCP1), super core promoter 2 (SCP2), or super core promoter 3 (SCP3). In some embodiments, the super core promoter is SCP1. The super core promoter may comprise from 5’ to 3’: a TATA box, an initiator motif (Inr), a motif ten element (MTE), and a downstream promoter element (DPE). The super core promoter may comprise one or more further core promoter elements, such as transcription binding sites (e.g. TFIIB recognition element). The core promoter elements may be in suitable relative positions to drive high levels of transcription. Suitably: (i) the TATA box is located from about -31 to about -26 relative to the super core promoter +1 transcription start site; (ii) the Inr is located from about -2 to about +4 relative to the super core promoter +1 transcription start site; (iii) the MTE is located from about +18 to about +27 relative to the super core promoter +1 transcription start site; and / or (iv) the DPE is located from about +28 to about +33 relative to the super core promoter +1 transcription start site. As a point of reference, the A in the Inr consensus is commonly designated as the +1 position in the promoter, whether or not the predominant site of initiation is at this nucleotide (see e.g. Kadonaga, J.T., 2012. Wiley Interdisciplinary Reviews: Developmental Biology, 1(1), pp.40-51). The core promoter elements may be operably linked. For example, the core promoter elements may be linked by linker sequences which permit the described components to function in their intended manner. Any suitable linker sequences can be used, for example linker sequences derived from core promoters (e.g. from the AdML core promoter, from the Drosophila G core promoter, or from the CMV IE1 core promoter). TATA box The TATA box is an A / T-rich sequence that is located approximately 26 to 31 nt upstream of the +1 transcription start site. In metazoans, the TATA box consensus is TATAWAAR, with the 5′ T generally being located at −30 or −31 relative to the +1 transcription start site. The TATA box is a recognition site for the binding of the TATA box-binding protein (TBP) subunit of TFIID. The TATA box may be derived from any suitable source. For example, the TATA box may be a CMV TATA box (e.g. a TATA box from the CMV IE1 core promoter). The TATA box may comprise or consist of the nucleotide sequence TATAWAAR. In some embodiments, the TATA box comprises or consists of the nucleotide sequence: TATAAAAA, TATAAAAG, TATATAAA, or TATATAAG. In some embodiments, the TATA box comprises or consists of the nucleotide sequence TATATAAG. Initiator (Inr) The Initiator (Inr) encompasses the +1 transcription start site and may be the most commonly occurring core promoter element. Although many factors have been found to interact with Inr sequences, it appears that basal transcription involves the binding of TFIID to the Inr. Based on functional studies that measure TFIID binding or transcriptional activity, the consensus sequences for the Inr are TCAKTY (A designated as +1) in Drosophila and YYANWYY (A+1) in humans. The Inr may be derived from any suitable source. For example, the Inr may be a CMV Inr (e.g. a TATA box from the CMV IE1 core promoter) or a composite Inr (e.g. based on sequences from AdML and Drosophila melanogaster G retrotransposon core promoter). The Inr may comprise or consist of the nucleotide sequence TCAKTY or YYANWYY. In some embodiments, the Inr comprises or consists of the nucleotide sequence TCAKTY. In some embodiments, the Inr comprises or consists of the nucleotide sequence TCAGTT, TCAGTC, TCATTT, or TCATTC. In some embodiments, the Inr comprises or consists of the nucleotide sequence TCAGTC. Motif ten element (MTE) and downstream promoter element (DPE) Both the MTE and DPE motifs are located downstream of the Inr and serve as recognition sites for the TAF6 and TAF9 subunits of TFIID. The MTE and DPE function in a cooperative manner with the Inr. The MTE may be derived from any suitable source. For example, the MTE may be a Tollo MTE (e.g. from the D. melanogaster Tollo core promoter). The MTE may comprise of consist of the nucleotide sequence CSARCSSAAC. In some embodiments, the MTE comprises of consists of the nucleotide sequence CGAACGGAAC, CGAACGCAAC, CGAACCGAAC, CGAGCGGAAC, CCAACGGAAC, CGAACCCAAC, CGAGCGCAAC, CCAACGCAAC, CGAGCCGAAC, CCAACCGAAC, CCAGCGGAAC, CGAGCCCAAC, CCAACCCAAC, CCAGCGCAAC, CCAGCCGAAC, or CCAGCCCAAC. In some embodiments, the MTE comprises or consists of the nucleotide sequence CGAGCCGAGC. The DPE may be derived from any suitable source. For example, the DPE may be a Drosophila G DPE (e.g. from the Drosophila G core promoter), a CALM2 DPE (e.g. from the human Calm2 core promoter), a IRF1 DPE (e.g. from the human IRF1 core promoter) or a TAF7 DPE (e.g. from the human TAF7 core promoter). Suitably, the DPE is a Drosophila G DPE or a CALM2 DPE. The DPE may comprise or consist of the nucleotide sequence RGWYVT. In some embodiments, the DPE comprises of consists of the nucleotide sequence AGACGT, AGACAT, AGATGT, AGTCGT, GGACGT, AGATAT, AGTCAT, GGACAT, AGTTGT, GGATGT, GGTCGT, AGTTAT, GGATAT, GGTCAT, GGTTGT, GGTTAT, AGACCT, AGATCT, AGTCCT, GGACCT, AGTTCT, GGATCT, GGTCCT, or GGTTCT. In some embodiments, the DPE comprises or consists of the nucleotide sequence AGACGT. SCP1 SCP1 may comprise from 5’ to 3’: a CMV TATA box, a composite Inr based on sequences from AdML and Drosophila melanogaster G retrotransposon core promoter, a Tollo MTE, and a Drosophila G DPE. Example SCP1 are provided in SEQ ID NOs: 5 to 7. In some embodiments, the SCP1 comprises or consists of a nucleotide sequence which is at least 70% identical to one or more of SEQ ID NOs: 5 to 7. Suitably, the SCP1 comprises or consists of 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%, or at least 99% identical to one or more of SEQ ID NOs: 5 to 7. In some embodiments, the SCP1 comprises or consists of the nucleotide sequence of one of SEQ ID NOs: 5 to 7. In some embodiments, the super core promoter comprises or consists of a nucleotide sequence which is at least 70% identical to SEQ ID NO: 5. Suitably, the super core promoter comprises or consists of 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%, or at least 99% identical to SEQ ID NO: 5. In some embodiments, the super core promoter comprises or consists of the nucleotide sequence SEQ ID NO: 5. gtacttatataagggggtgggggcgcgttcgtcctcagtcgcgatcgaacactcgagccgagcagacgt gcctacggaccg Example SCP1 (SEQ ID NO: 5) In some embodiments, the super core promoter comprises or consists of a nucleotide sequence which is at least 70% identical to SEQ ID NO: 6. Suitably, the super core promoter comprises or consists of 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%, or at least 99% identical to SEQ ID NO: 6. In some embodiments, the super core promoter comprises or consists of the nucleotide sequence SEQ ID NO: 6. gtacttatataagggggtgggggcgcgttcgtcttcagttttttttcaacactcgagccgagcagacgt gcctacggaccg Example SCP1 variant 1 (SEQ ID NO: 6) In some embodiments, the super core promoter comprises or consists of a nucleotide sequence which is at least 70% identical to SEQ ID NO: 7. Suitably, the super core promoter comprises or consists of 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%, or at least 99% identical to SEQ ID NO: 7. In some embodiments, the super core promoter comprises or consists of the nucleotide sequence SEQ ID NO: 7. gtacttatataagggggtgggggcgcgttcgtcttcagtttcgtttcaacactcgagccgagcagacgt gcctacggaccg Example SCP1 variant 2 (SEQ ID NO: 7) SCP2 SCP2 may comprise from 5’ to 3’: a CMV TATA box, a CMV Inr, a Tollo MTE, and a CALM2 DPE. In some embodiments, the super core promoter comprises or consists of a nucleotide sequence which is at least 70% identical to SEQ ID NO: 8. Suitably, the super core promoter comprises or consists of 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%, or at least 99% identical to SEQ ID NO: 8. In some embodiments, the super core promoter comprises or consists of the nucleotide sequence SEQ ID NO: 8. aggtctatataagcagagctcgtttagtgaaccgtcagatcgcctggagacgtcgagccgagtggttgt gcctccatagaa Example SCP2 (SEQ ID NO: 8) SCP3 SCP3 may be a variant of SCP2 which has one or more point mutations (e.g. four point mutations) which enhance its ability to drive high levels of transcription. For example: (i) the A in position +3 may be changed to T (as the T matches the Drosophila Inr consensus and is common in many DPE- and MTE- containing promoters); (ii) the T in position +4 may be changed to C (as it matches the Inr of both the human DPE-containing Calm2 promoter and the SCP1); (iii) G in position +16 may be changed to C (based on single nucleotide analysis of the Tollo MTE); and (iv) T in position +31 may be changed to C (as many DPE- driven genes and several MTE-driven genes contain C in this position). In some embodiments, the super core promoter comprises or consists of a nucleotide sequence which is at least 70% identical to SEQ ID NO: 9. Suitably, the super core promoter comprises or consists of 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%, or at least 99% identical to SEQ ID NO: 9. In some embodiments, the super core promoter comprises or consists of the nucleotide sequence SEQ ID NO: 9. aggtctatataagcagagctcgtttagtgaaccgtcagtccgcctggagacctcgagccgagtggtcgt gcctccatagaa Example SCP3 (SEQ ID NO: 9) Spliceosomal introns In some embodiments, the regulatory element comprises or consists of a spliceosomal intron or a fragment thereof comprising a branch point sequence, a polypyrimidine tract, and a 3’ splice acceptor site. 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: 10. The RBG intron II may comprise or consist of the nucleotide sequence of SEQ ID NO: 11. gttggtatcctttttacagcacaacttaatgagacagatagaaactggtcttgtagaaacag agtagtcgcctgcttttctgccaggtgctgacttctctcccctgggctgttttcattttctc agg Rabbit beta globin intron I (SEQ ID NO: 10) gtgagtttggggacccttgattgttctttctttttcgctattgtaaaattcatgttatatgg agggggcaaagttttcagggtgttgtttagaatgggaagatgtcccttgtatcaccatggac cctcatgataattttgtttctttcactttctactctgttgacaaccattgtctcctcttatt ttcttttcattttctgtaactttttcgttaaactttagcttgcatttgtaacgaatttttaa attcacttttgtttatttgtcagattgtaagtactttctctaatcacttttttttcaaggca atcagggtatattatattgtacttcagcacagttttagagaacaattgttataattaaatga taaggtagaatatttctgcatataaattctggctggcgtggaaatattcttattggtagaaa caactacatcctggtcatcatcctgcctttctctttatggttacaatgatatacactgtttg agatgaggataaaatactctgagtccaaaccgggcccctctgctaaccatgttcatgccttc ttctttttcctacagc Rabbit beta globin intron II (SEQ ID NO: 11) 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: 12. 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: 12) 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: 13. In some embodiments, the spliceosomal intron does not comprise the nucleotide sequence of SEQ ID NO: 13. gtaagtttaaagctcaggtcgagaccgggcctttgtccggcgctcccttggagcctacctag actcagccggctctccacgctttgcctgaccctgcttgctcaactct HTLV-IR 5′ intronic splice donor region (SEQ ID NO: 13) 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: 14. 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: 14) 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: 14. In some embodiments, the regulatory element comprises or consists of a nucleotide sequence having 90% or more sequence identity to SEQ ID NO: 14. In some embodiments, the regulatory element comprises or consists of a nucleotide sequence having 95% or more sequence identity to SEQ ID NO: 14. In some embodiments, the regulatory element comprises or consists of a nucleotide sequence having 96% or more sequence identity to SEQ ID NO: 14. In some embodiments, the regulatory element comprises or consists of a nucleotide sequence having 97% or more sequence identity to SEQ ID NO: 14. In some embodiments, the regulatory element comprises or consists of a nucleotide sequence having 98% or more sequence identity to SEQ ID NO: 14. In some embodiments, the regulatory element comprises or consists of a nucleotide sequence having 99% or more sequence identity to SEQ ID NO: 14. In some embodiments, the regulatory element comprises or consists of the nucleotide sequence SEQ ID NO: 14, 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: 14, 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: 14. Another example regulatory element derived from the RBG intron I is provided below in SEQ ID NO: 15. Compared to SEQ ID NO: 15, 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: 15) 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: 15. In some embodiments, the regulatory element comprises or consists of a nucleotide sequence having 90% or more sequence identity to SEQ ID NO: 15. In some embodiments, the regulatory element comprises or consists of a nucleotide sequence having 95% or more sequence identity to SEQ ID NO: 15. In some embodiments, the regulatory element comprises or consists of a nucleotide sequence having 96% or more sequence identity to SEQ ID NO: 15. In some embodiments, the regulatory element comprises or consists of a nucleotide sequence having 97% or more sequence identity to SEQ ID NO: 15. In some embodiments, the regulatory element comprises or consists of a nucleotide sequence having 98% or more sequence identity to SEQ ID NO: 15. In some embodiments, the regulatory element comprises or consists of a nucleotide sequence having 99% or more sequence identity to SEQ ID NO: 15. In some embodiments, the regulatory element comprises or consists of the nucleotide sequence SEQ ID NO: 15, 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: 15, 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: 15. In some embodiments, the regulatory element consists of the nucleotide sequence SEQ ID NO: 15, 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: 15, 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: 15. 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: 13. In some embodiments, the regulatory element does not comprise the nucleotide sequence of SEQ ID NO: 13. Hybrid promoters In some embodiments, the polynucleotide of the present invention comprises a hybrid promoter comprising a kidney-specific promoter and a regulatory element. As used herein, a “hybrid promoter” or “composite promoter” may refer to a synthetic promoter comprising a combination of elements derived from different promoters. For example, a hybrid promoter may comprise a proximal promoter region derived from one pre-existing promoter and a core promoter from another pre-existing promoter to achieve the desired expression levels. A muscle hybrid promoter is described in Piekarowicz, K., et al. (2019). Methods & clinical development, 15, 157–169. Suitably, the kidney-specific promoter may comprise or consist of a proximal promoter region and the super core promoter may comprise or consist of a core promoter region. The hybrid promoter may be a tissue-specific promoter. The hybrid promoter may be a kidney- specific promoter. In some embodiments, the hybrid promoter is a glomerular-specific promoter. In preferred embodiments, the hybrid promoter is a podocyte-specific promoter. The hybrid promoter may be a strong promoter. As used herein, a “strong promoter” may refer to a promoter which facilitates high expression of a protein-coding sequence. Genes regulated by strong promoters yield more mRNA and therefore more product protein than genes regulated by weak promoters. The intrinsic strength of a promoter may be associated with the core promoter sequences. Higher expression may be measured for example by measuring the expression of a protein-coding sequence, e.g. GFP, operably linked to the promoter, wherein expression of the protein-coding sequence correlates with the ability of the promoter to facilitate expression of a gene. The hybrid promoter may be a strong kidney-specific promoter. In some embodiments, the hybrid promoter is a strong glomerular-specific promoter. In preferred embodiments, the hybrid promoter is a strong podocyte-specific promoter. Example hybrid promoter comprising a super core promoter In some embodiments, the polynucleotide of the present invention comprises a hybrid promoter comprising a kidney-specific promoter and a super core promoter. In one aspect, the present invention provides a polynucleotide comprising: a 5’ ITR; a hybrid promoter comprising a kidney-specific promoter and a super core promoter; a protein coding sequence encoding a complement inhibitor; optionally, a Woodchuck Hepatitis Virus Post- transcriptional Regulatory Element (WPRE); optionally, a polyadenylation sequence; and a 3’ ITR. In some embodiments, the polynucleotide comprises from 5’ to 3’: a 5’ ITR; a hybrid promoter comprising a kidney-specific promoter and a super core promoter; a protein coding sequence encoding a complement inhibitor; optionally, a Woodchuck Hepatitis Virus Post-transcriptional Regulatory Element (WPRE); optionally, a polyadenylation sequence; and a 3’ ITR. The kidney-specific promoter may be any described herein in the section entitled “Kidney- specific promoters”. The super core promoter may be any described herein in the section entitled “Super core promoters”. The kidney-specific promoter may be upstream or downstream of the super core promoter. In some embodiments, the kidney-specific promoter is upstream of the super core promoter. The kidney-specific promoter and the super core promoter may be operably linked. The kidney-specific promoter and the super core promoter may be located such that the promoter of the present invention facilitates high tissue-specific (e.g. kidney- or podocyte-specific) expression of a protein-coding sequence. The hybrid promoter may comprise or consist of from 5’ to 3’: a kidney-specific promoter, optionally a linker sequence, and a super core promoter; or a super core promoter, optionally a linker sequence, and a kidney-specific promoter. In some embodiments, the hybrid promoter comprises or consists of from 5’ to 3’: a kidney-specific promoter, optionally a linker sequence, and a super core promoter. As used herein, a “linker sequence” may refer to any sequence which permits the described components to function in their intended manner. Suitably, the optional linker sequence linking the kidney-specific promoter and the super core promoter does not have a negative effect on the promoter function. Suitably, a linker 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). The linker sequence may comprise, for example, at least 1 bp (e.g.1, 2, 3, 4, 5, 6, 7, 8, 9, 10), at least 2 bp, at least 3 bp, at least 4 bp, at least 5 bp, at least 6 bp, at least 7 bp, at least 8 bp, at least 9 bp, or at least 10 bp. The linker sequence may comprise, for example, about 500 bp or fewer, about 400 bp or fewer, about 300 bp or fewer, about 200 bp or fewer, about 150 bp or fewer, about 100 bp or fewer, about 90 bp or fewer, about 80 bp or fewer, about 70 bp or fewer, about 60 bp or fewer, or about 50 bp or fewer. Suitably, a linker sequence has a length of about 1 bp to about 200 bp, about 1 bp to about 100 bp, about 1 bp to about 90 bp, about 1 bp to about 80 bp, about 1 bp to about 70 bp, about 1 bp to about 60 bp, or about 1 bp to about 50 bp. Suitably, a linker sequence has a length of about 10 bp to about 200 bp, about 10 bp to about 100 bp, about 10 bp to about 90 bp, about 10 bp to about 80 bp, about 10 bp to about 70 bp, about 10 bp to about 60 bp, or about 10 bp to about 50 bp. Example linker sequences based on random shuffled DNA sequences are provided below: Example linker sequence Length gcaggtcacg (SEQ ID NO: 16)10bptcgaactggacatga (SEQ ID NO: 17)15bptgtcagaaaagcggtcat (SEQ ID NO: 18)18bptggcgtatatgccggcaaca (SEQ ID NO: 19)20bpccggatcggtaagagaaagctcatt (SEQ ID NO: 20)25bpacatacggtaccgggtcgaatggaatgcct (SEQ ID NO: 21)30bpgcttgtagatggccaattgagctcccaggcatgacttaat (SEQ ID NO: 22)40bpcataccccgtcttctggccaagtggcaagtctatgagcggtgtatgaacaaatcggtc 60bp at (SEQ ID NO: 23) gaactgaccgaattaccagccctctagaaaaccaagtagcaaagccaggtttcgccca 80bp tggctcatcgtcagctgaccgg (SEQ ID NO: 24) aaagacaaggagggggtgatgtcggcaggttaccacaccggcggaacatgatatttag 100bp aatgtacgccgcggttatccccccgttttaacctaacttcgt (SEQ ID NO: 25) Other example linker sequences are provided below: Example linker sequence Length gaattcccctggg (SEQ ID NO: 26)13bpcttaaggctggcggttataagtgactaactcccgtcagaacccctggg (SEQ ID NO: 27)48bpcccggattattcataccgtcccaccatcgggcgcggatcccggtccgaagcgcgcgga attcccctggg (SEQ ID NO: 28) 69bp In some embodiments, the hybrid promoter comprises or consists of from 5’ to 3’: a kidney- specific promoter, a linker sequence, and a super core promoter. In some embodiments, the kidney-specific promoter and the super core promoter are directly linked (i.e. no linker sequence is present). The hybrid promoter may further comprise any other suitable elements, such as additional transcription factor binding regions and / or one or more further linker sequences. Example minimal NPHS1-SCP1 hybrid promoter In some embodiments, the hybrid promoter comprises a minimal NPHS1 promoter and SCP1. In some embodiments, the hybrid promoter comprises or consists of from 5’ to 3’: a minimal NPHS1 promoter, optionally a linker sequence, and SCP1. In some embodiments, the hybrid promoter comprises or consists of a minimal 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: 2 and a super core 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: 5. In some embodiments, the hybrid promoter comprises or consists of a minimal NPHS1 promoter comprising or consisting of a nucleotide sequence having 70% or more sequence identity to SEQ ID NO: 2 and a super core promoter comprising or consisting of a nucleotide sequence having 70% or more sequence identity to SEQ ID NO: 5. In some embodiments, the hybrid promoter comprises or consists of a minimal NPHS1 promoter comprising or consisting of a nucleotide sequence having 75% or more sequence identity to SEQ ID NO: 2 and a super core promoter comprising or consisting of a nucleotide sequence having 75% or more sequence identity to SEQ ID NO: 5. In some embodiments, the hybrid promoter comprises or consists of a minimal NPHS1 promoter comprising or consisting of a nucleotide sequence having 80% or more sequence identity to SEQ ID NO: 2 and a super core promoter comprising or consisting of a nucleotide sequence having 80% or more sequence identity to SEQ ID NO: 5. In some embodiments, the hybrid promoter comprises or consists of a minimal NPHS1 promoter comprising or consisting of a nucleotide sequence having 85% or more sequence identity to SEQ ID NO: 2 and a super core promoter comprising or consisting of a nucleotide sequence having 85% or more sequence identity to SEQ ID NO: 5. In some embodiments, the hybrid promoter comprises or consists of a minimal NPHS1 promoter comprising or consisting of a nucleotide sequence having 90% or more sequence identity to SEQ ID NO: 2 and a super core promoter comprising or consisting of a nucleotide sequence having 90% or more sequence identity to SEQ ID NO: 5. In some embodiments, the hybrid promoter comprises or consists of a minimal NPHS1 promoter comprising or consisting of a nucleotide sequence having 95% or more sequence identity to SEQ ID NO: 2 and a super core promoter comprising or consisting of a nucleotide sequence having 95% or more sequence identity to SEQ ID NO: 5. In some embodiments, the hybrid promoter comprises or consists of a minimal NPHS1 promoter comprising or consisting of a nucleotide sequence having 96% or more sequence identity to SEQ ID NO: 2 and a super core promoter comprising or consisting of a nucleotide sequence having 96% or more sequence identity to SEQ ID NO: 5. In some embodiments, the hybrid promoter comprises or consists of a minimal NPHS1 promoter comprising or consisting of a nucleotide sequence having 97% or more sequence identity to SEQ ID NO: 2 and a super core promoter comprising or consisting of a nucleotide sequence having 97% or more sequence identity to SEQ ID NO: 5. In some embodiments, the hybrid promoter comprises or consists of a minimal NPHS1 promoter comprising or consisting of a nucleotide sequence having 98% or more sequence identity to SEQ ID NO: 2 and a super core promoter comprising or consisting of a nucleotide sequence having 98% or more sequence identity to SEQ ID NO: 5. In some embodiments, the hybrid promoter comprises or consists of a minimal NPHS1 promoter comprising or consisting of a nucleotide sequence having 99% or more sequence identity to SEQ ID NO: 2 and a super core promoter comprising or consisting of a nucleotide sequence having 99% or more sequence identity to SEQ ID NO: 5. In some embodiments, the hybrid promoter comprises or consists of a minimal NPHS1 promoter comprising or consisting of the nucleotide sequence of SEQ ID NO: 2 and a super core promoter comprising or consisting of the nucleotide sequence of SEQ ID NO: 5. In some embodiments, the hybrid promoter comprises or consists of a minimal NPHS1 promoter consisting of the nucleotide sequence of SEQ ID NO: 2 and a super core promoter consisting of the nucleotide sequence of SEQ ID NO: 5. In some embodiments, the hybrid promoter comprises or consists of a nucleotide sequence which is at least 70% identical to SEQ ID NO: 29. Suitably, the hybrid promoter 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: 29. In some embodiments, the hybrid promoter comprises or consists of the nucleotide sequence SEQ ID NO: 29. ggccctggggtcacggaggctggggaggcaccgaggaacgcgcctggcatgtgctgacaggggatttta tgctccaggagcaagacagagagagatactcacagggaagaggggaagaggaaaacgagaaagggagga gagtaacggaaagagataaaaaagaaaagcaggtggcagagacacacagagagggacccagagaaagcc agacagacgcaggtggctggcagcgggcgctgtgggggtcacagtagggggacctgtg(n)gtactta tataagggggtgggggcgcgttcgtcctcagtcgcgatcgaacactcgagccgagcagacgtgcctacg gaccg wherein x is from 0 to 100 Example minimal NPHS1-SCP1 hybrid promoter (SEQ ID NO: 29) 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: 16-28. Example hybrid promoters comprising a spliceosomal intron or a fragment thereof In some embodiments, the polynucleotide of the present invention comprises a hybrid promoter comprising a kidney-specific promoter and a spliceosomal intron or a fragment thereof comprising a branch point sequence, a polypyrimidine tract, and a 3’ splice acceptor site. In one aspect, the present invention provides a polynucleotide comprising: a 5’ ITR; a hybrid promoter comprising a kidney-specific promoter and 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 a complement inhibitor; optionally, a Woodchuck Hepatitis Virus Post-transcriptional Regulatory Element (WPRE); optionally, a polyadenylation sequence; and a 3’ ITR. In some embodiments, the polynucleotide comprises from 5’ to 3’: a 5’ ITR; a hybrid promoter comprising a kidney-specific promoter and 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 a complement inhibitor; optionally, a Woodchuck Hepatitis Virus Post-transcriptional Regulatory Element (WPRE); optionally, a polyadenylation sequence; and a 3’ ITR. The kidney-specific promoter may be any described herein in the section entitled “Kidney- specific promoters”. The spliceosomal intron or fragment thereof may be any described herein in the section entitled “Spliceosomal introns”. The kidney-specific promoter may be upstream or downstream of the spliceosomal intron or fragment thereof. In some embodiments, the kidney-specific promoter is upstream of the spliceosomal intron or fragment thereof. The kidney-specific promoter and the spliceosomal intron or fragment thereof may be operably linked. The kidney-specific promoter and the spliceosomal intron or fragment thereof may be located such that the promoter of the present invention facilitates high tissue-specific (e.g. kidney- or podocyte-specific) expression of a protein-coding sequence. The hybrid promoter may comprise or consist of from 5’ to 3’: a kidney-specific promoter, optionally a linker sequence, and a spliceosomal intron or fragment thereof; or a spliceosomal intron or fragment thereof, optionally a linker sequence, and a kidney-specific promoter. In some embodiments, the hybrid promoter comprises or consists of from 5’ to 3’: a kidney- specific promoter, optionally a linker sequence, and a spliceosomal intron or fragment thereof. In some embodiments, the hybrid promoter comprises or consists of from 5’ to 3’: a kidney- specific promoter, a linker sequence, and a spliceosomal intron or fragment thereof. Suitable linker sequences are described above. In some embodiments, the kidney-specific promoter and the spliceosomal intron or fragment thereof are directly linked (i.e. no linker sequence is present). The hybrid promoter may further comprise any other suitable elements, such as additional transcription factor binding regions and / or one or more further linker sequences. Example minimal NPHS1-regulatory element hybrid promoter In some embodiments, the hybrid promoter comprises a minimal NPHS1 promoter and a spliceosomal intron or a fragment thereof comprising a branch point sequence, a polypyrimidine tract, and a 3’ splice acceptor site. In some embodiments, the hybrid promoter comprises or consists of from 5’ to 3’: a minimal NPHS1 promoter, optionally a linker sequence, and a spliceosomal intron or a fragment thereof comprising a branch point sequence, a polypyrimidine tract, and a 3’ splice acceptor site. In some embodiments, the hybrid promoter comprises or consists of a minimal 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: 2 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: 15. In some embodiments, the hybrid promoter comprises or consists of a minimal NPHS1 promoter comprising or consisting of a nucleotide sequence having 70% or more sequence identity to SEQ ID NO: 2 and a regulatory element comprising or consisting of a nucleotide sequence having 70% or more sequence identity to SEQ ID NO: 15. In some embodiments, the hybrid promoter comprises or consists of a minimal NPHS1 promoter comprising or consisting of a nucleotide sequence having 75% or more sequence identity to SEQ ID NO: 2 and a regulatory element comprising or consisting of a nucleotide sequence having 75% or more sequence identity to SEQ ID NO: 15. In some embodiments, the hybrid promoter comprises or consists of a minimal NPHS1 promoter comprising or consisting of a nucleotide sequence having 80% or more sequence identity to SEQ ID NO: 2 and a regulatory element comprising or consisting of a nucleotide sequence having 80% or more sequence identity to SEQ ID NO: 15. In some embodiments, the hybrid promoter comprises or consists of a minimal NPHS1 promoter comprising or consisting of a nucleotide sequence having 85% or more sequence identity to SEQ ID NO: 2 and a regulatory element comprising or consisting of a nucleotide sequence having 85% or more sequence identity to SEQ ID NO: 15. In some embodiments, the hybrid promoter comprises or consists of a minimal NPHS1 promoter comprising or consisting of a nucleotide sequence having 90% or more sequence identity to SEQ ID NO: 2 and a regulatory element comprising or consisting of a nucleotide sequence having 90% or more sequence identity to SEQ ID NO: 15. In some embodiments, the hybrid promoter comprises or consists of a minimal NPHS1 promoter comprising or consisting of a nucleotide sequence having 95% or more sequence identity to SEQ ID NO: 2 and a regulatory element comprising or consisting of a nucleotide sequence having 95% or more sequence identity to SEQ ID NO: 15. In some embodiments, the hybrid promoter comprises or consists of a minimal NPHS1 promoter comprising or consisting of a nucleotide sequence having 96% or more sequence identity to SEQ ID NO: 2 and a regulatory element comprising or consisting of a nucleotide sequence having 96% or more sequence identity to SEQ ID NO: 15. In some embodiments, the hybrid promoter comprises or consists of a minimal NPHS1 promoter comprising or consisting of a nucleotide sequence having 97% or more sequence identity to SEQ ID NO: 2 and a regulatory element comprising or consisting of a nucleotide sequence having 97% or more sequence identity to SEQ ID NO: 15. In some embodiments, the hybrid promoter comprises or consists of a minimal NPHS1 promoter comprising or consisting of a nucleotide sequence having 98% or more sequence identity to SEQ ID NO: 2 and a regulatory element comprising or consisting of a nucleotide sequence having 98% or more sequence identity to SEQ ID NO: 15. In some embodiments, the hybrid promoter comprises or consists of a minimal NPHS1 promoter comprising or consisting of a nucleotide sequence having 99% or more sequence identity to SEQ ID NO: 2 and a regulatory element comprising or consisting of a nucleotide sequence having 99% or more sequence identity to SEQ ID NO: 15. In some embodiments, the hybrid promoter comprises or consists of a minimal NPHS1 promoter comprising or consisting of the nucleotide sequence of SEQ ID NO: 2 and a regulatory element comprising or consisting of the nucleotide sequence of SEQ ID NO: 15. In some embodiments, the hybrid promoter comprises or consists of a minimal NPHS1 promoter consisting of the nucleotide sequence of SEQ ID NO: 2 and a regulatory element consisting of the nucleotide sequence of SEQ ID NO: 15. In some embodiments, the hybrid promoter comprises or consists of a nucleotide sequence which is at least 70% identical to SEQ ID NO: 30. Suitably, the hybrid promoter comprises or consists of 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: 30. In some embodiments, the hybrid promoter comprises or consists of the nucleotide sequence SEQ ID NO: 30. ggccctggggtcacggaggctggggaggcaccgaggaacgcgcctggcatgtgctgacaggg gattttatgctccaggagcaagacagagagagatactcacagggaagaggggaagaggaaaa cgagaaagggaggagagtaacggaaagagataaaaaagaaaagcaggtggcagagacacaca gagagggacccagagaaagccagacagacgcaggtggctggcagcgggcgctgtgggggtca cagtagggggacctgtg(n)agttctctcgttaacttaatgagacagatagaaactggtctt gtagaaacagagtagtcgcctgcttttctgccaggtgctgacttctctcccctgggcttttt tctttttctcagg wherein x is from 0 to 100 Example minimal NPHS1 promoter-regulatory element (SEQ ID NO: 30) 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)x is selected from any of SEQ ID NOs: 16-28. Protein-coding sequences The polynucleotide of the present invention comprises a protein-coding sequence encoding one or more inhibitor of the complement system. As used herein, an “inhibitor of the complement system” or “complement inhibitor” is a protein which prevents activation of the complement system. Complement is tightly controlled by these inhibitors, which naturally protect self-cells and tissues from unwanted complement activation. Complement inhibitors can regulate complement activation in different stages of the classical, lectin, and alternative pathways. Suitably, the complement inhibitor is a naturally- occurring complement inhibitor, or a fragment and / or variant thereof. Preferably, the inhibitor of the complement system is an inhibitor of the complement system in humans. Complement inhibitors are grouped into two categories: soluble inhibitors and membrane- bound inhibitors. Preferably, the inhibitor of the complement system is a soluble complement inhibitor. Soluble complement inhibitors include C1 inhibitor (C1INH), complement factor I (CFI), complement factor H (CFH), complement factor H-like protein 1 (FHL-1), C4 binding protein (C4BP), clusterin and vitronectin. Membrane-bound regulators include CD46, CD55, CD59, CD35 and CUB and Sushi multiple domain 1 (CSMD1). The inhibitor of the complement system may be selected from: CFI, CFH, FHL-1, C1INH, C4BP, CD46, CD55, CD59, CD35, vitronectin, clusterin, and CSMD1. Preferably, the inhibitor of the complement system is selected from: CFI, CFH, and FHL-1. 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. CFI In some embodiments, the protein-coding sequence encodes CFI. Complement factor I (CFI) is a trypsin-like serine protease that inhibits the complement system by cleaving three peptide bonds in the alpha-chain of C3b and two bonds in the alpha-chain of C4b thereby inactivating these proteins. CFI is a glycoprotein heterodimer consisting of a disulfide linked heavy chain and light chain. The heavy chain has four domains: an FI membrane attack complex (FIMAC) domain, CD5 domain, and low density lipoprotein receptor 1 and 2 (LDLr1 and LDLr2) domains. The heavy chain plays an inhibitory role in maintaining the enzyme inactive until it meets the complex formed by the substrate (either C3b or C4b) and a cofactor protein (Factor H, C4b-binding protein, complement receptor 1, and membrane cofactor protein). Upon binding of the enzyme to the substrate:cofactor complex, the heavy:light chain interface is disrupted, and the enzyme activated by allostery. The light chain contains only the serine protease domain. This domain contains the catalytic triad His-362, Asp-411, and Ser-507, which is responsible for specific cleavage of C3b and C4b. CFI is encoded by the CFI gene. The CFI gene is conserved in humans, chimpanzees, dogs, cows, mice, and rats. In preferred embodiments, the CFI is a human CFI. A human CFI may consist of a polypeptide sequence of UniProtKB accession P05156. In some embodiments, the CFI comprises or consists of an amino acid sequence which is at least 70% identical to SEQ ID NO: 31. Suitably, the CFI 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: 31. In some embodiments, the CFI comprises or consists of the amino acid sequence of SEQ ID NO: 31. In some embodiments, the CFI consists of an amino acid sequence which is at least 70% identical to SEQ ID NO: 31. Suitably, the CFI 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: 31. In some embodiments, the CFI consists of the amino acid sequence of SEQ ID NO: 31. MKLLHVFLLFLCFHLRFCKVTYTSQEDLVEKKCLAKKYTHLSCDKVFCQPWQRCIEGTCVCK LPYQCPKNGTAVCATNRRSFPTYCQQKSLECLHPGTKFLNNGTCTAEGKFSVSLKHGNTDSE GIVEVKLVDQDKTMFICKSSWSMREANVACLDLGFQQGADTQRRFKLSDLSINSTECLHVHC RGLETSLAECTFTKRRTMGYQDFADVVCYTQKADSPMDDFFQCVNGKYISQMKACDGINDCG DQSDELCCKACQGKGFHCKSGVCIPSQYQCNGEVDCITGEDEVGCAGFASVTQEETEILTAD MDAERRRIKSLLPKLSCGVKNRMHIRRKRIVGGKRAQLGDLPWQVAIKDASGITCGGIYIGG CWILTAAHCLRASKTHRYQIWTTVVDWIHPDLKRIVIEYVDRIIFHENYNAGTYQNDIALIE MKKDGNKKDCELPRSIPACVPWSPYLFQPNDTCIVSGWGREKDNERVFSLQWGEVKLISNCS KFYGNRFYEKEMECAGTYDGSIDACKGDSGGPLVCMDANNVTYVWGVVSWGENCGKPEFPGV YTKVANYFDWISYHVGRPFISQYNV Example CFI amino acid sequence (SEQ ID NO: 31) In preferred embodiments, the protein-coding sequence encodes a full-length wild-type CFI. In more preferred embodiments, the protein-coding sequence encodes a full-length wild-type human CFI. Although it is preferred that the protein-coding sequence encodes a full-length wild-type CFI, the protein-coding sequence may alternatively encode a fragment and / or variant of CFI that retains CFI activity. For example, a fragment and / or variant of CFI that is capable of cleaving C3b into iC3b and / or capable of cleaving iC3b into C3d,g. The fragment and / or variant of CFI may retain at least 50%, 60%, 70%, 80%, 90%, 95% or 100% of the C3b-inactivating and iC3b-degradation activity of native CFI. The C3b-inactivating and iC3b-degradation activity of the fragment and / or variant of CFI and native CFI, may be determined using any suitable method known to those of skill in the art. For example, using a proteolytic assay. In some embodiments, the CFI comprises or consists of an amino acid sequence which is at least 70% identical to SEQ ID NO: 32. Suitably, the CFI 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: 32. In some embodiments, the CFI comprises or consists of the amino acid sequence of SEQ ID NO: 32. In some embodiments, the CFI consists of an amino acid sequence which is at least 70% identical to SEQ ID NO: 32. Suitably, the CFI 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: 32. In some embodiments, the CFI consists of the amino acid sequence of SEQ ID NO: 32. MKLLHVFLLFLCFHLRFCKVTYTSQEDLVEKKCLAKKYTHLSCDKVFCQPWQLCIEGTCVCK LPYQCPKNGTAVCATNRRSFPTYCQQKSLECLHPGTKFLNNGTCTAEGKFSVSLKHGNTDSE GIVEVKLVDQDKTMFICKSSWSMREANVACLDLGFQQGADTQRRFKLSDLSINSTECLHVHC RGLETSLAECTFTKRRTMGYQDFADVVCYTQKADSPMDDFFQCVNGKYISQMKACDGINDCG DQSDELCCKACQGKGFHCKSGVCIPSQYQCNGEVDCITGEDEVGCAGFASVTQEETEILTAD MDAERRRIKSLLPKLSCGVKNRMHIRRKRIVGGKRAQLGDLPWQVAIKDASGITCGGIYIGG CWILTAAHCLYASKTHRYQIWTTVVDWIHPDLKRIVIEYVDRIIFHENYNAGTYQNDIALIE MKKDGNKKDCELPRSIPACVPWSPYLFQPNDTCIVSGWGREKDNERVFSLQWGEVKLISNCS KFYGNRFYEKEMECAGTYDGSIDACKGDSGGPLVCMDANNVTYVWGVVSWGENCGKPEFPGV YTKVANYFDWISYHVGRPFISQYNV Example CFI amino acid sequence (mutant) (SEQ ID NO: 32) A person skilled in the art would be able to generate fragments and / or variants of CFI using conservative substitutions, based on the known structural and functional features of CFI (see e.g. Roversi, P., et al., 2011. PNAS, 108(31), pp.12839-12844), and / or based on known variants (see e.g. NCBI Gene ID: 3426 and NCBI HomoloGene: 171). Suitably, a fragment and / or variant of CFI comprises a heavy chain comprising an FI membrane attack complex (FIMAC) domain, a CD5 domain, and low density lipoprotein receptor 1 and 2 (LDLr1 and LDLr2) domains; and a light chain comprising a serine protease domain. Example nucleotide sequences encoding CFI are provided by SEQ ID NOs: 33 to 35. In some embodiments, the protein-coding sequence comprises or consists of a nucleotide sequence which is at least 70% identical to SEQ ID NO: 33. Suitably, the protein-coding sequence 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: 33. In some embodiments, the protein-coding sequence comprises or consists of the nucleotide sequence of SEQ ID NO: 33. In some embodiments, the protein-coding sequence consists of a nucleotide sequence which is at least 70% identical to SEQ ID NO: 33. Suitably, the protein-coding sequence 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: 33. In preferred embodiments, the protein-coding sequence consists of the nucleotide sequence of SEQ ID NO: 33. atgaagctgctgcatgtgttcctgttgttcctgtgttttcacctgagattttgtaaggtgac ttataccagccaggaagacctggtagagaagaagtgcctggccaagaagtatactcacctgt cttgcgataaggtgttctgccagccttggcagcggtgcatcgagggcacctgtgtgtgcaag ctgccctatcagtgtcccaagaatgggaccgccgtgtgtgccaccaacagaaggagcttccc cacctattgccagcagaagagcctggagtgtctgcaccccggcaccaagttcctgaataatg gcacatgtaccgccgagggcaagttctcagtctccctgaagcatggcaacactgacagtgag ggcatcgtggaggtgaaactggtggaccaggacaagacaatgttcatctgtaagtcatcttg gtctatgcgggaggccaacgtggcctgcctggatctgggcttccagcagggggccgataccc agaggcgattcaagctgagcgatctgtctataaacagcaccgagtgcctgcacgtgcactgc aggggcctggaaacctctctggccgaatgcaccttcaccaagagacggactatgggctacca ggattttgccgatgtggtgtgctatacccagaaagccgactcccccatggacgacttcttcc aatgtgtcaatggaaagtacatcagtcagatgaaggcatgtgacggcattaacgattgtggc gatcagagcgatgagctgtgctgtaaggcctgccagggaaagggcttccactgcaaatccgg cgtgtgcatccctagccagtaccagtgtaatggcgaggtggactgtatcacaggagaggacg aagtgggatgcgctggattcgctagtgtgacccaggaggagaccgagatcctgaccgccgac atggatgccgagaggagacgtatcaagtccctgctgcctaagctgtcttgtggagtgaagaa taggatgcacatcagacgcaagagaatcgtcggcggcaagcgcgcccagctgggcgatctgc cctggcaagtggccattaaggacgcctccggcatcacatgtggaggaatatacataggcggg tgctggatcctgaccgccgcccactgcctgcgggcctctaaaactcataggtaccagatctg gacaaccgtggtggattggatccatcctgatctgaagagaatcgtgatcgagtacgtcgata ggattatctttcacgagaactataatgccgggacctaccagaatgacatcgctctcattgag atgaagaaggatggcaacaagaaggactgcgagctgcccaggagcattcccgcttgcgtgcc atggtccccatacctgttccagccaaacgacacctgcatcgtgagcggctggggcagagaaa aggacaacgagagagtgttctccctgcagtggggcgaagtgaagctgatttccaactgcagt aagttctacggcaaccgcttctatgagaaggagatggagtgtgccggcacatacgacggcag catcgacgcctgcaagggcgacagcggcggccccctggtgtgcatggacgccaacaacgtga cctatgtgtggggggtggtgtcctggggcgagaactgtggaaagccagagttccctggagtg tataccaaggtggccaactacttcgattggatcagctaccacgtcggcaggcccttcatcag ccagtacaacgtttaa Example CFI polynucleotide (codon-optimised) (SEQ ID NO: 33) In some embodiments, the protein-coding sequence comprises or consists of a nucleotide sequence which is at least 70% identical to SEQ ID NO: 34. Suitably, the protein-coding sequence 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: 34. In some embodiments, the protein-coding sequence comprises or consists of the nucleotide sequence of SEQ ID NO: 34. In some embodiments, the protein-coding sequence consists of a nucleotide sequence which is at least 70% identical to SEQ ID NO: 34. Suitably, the protein-coding sequence 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: 34. In preferred embodiments, the protein-coding sequence consists of the nucleotide sequence of SEQ ID NO: 34. atgaagcttcttcatgttttcctgttatttctgtgcttccacttaaggttttgcaaggtcac ttatacatctcaagaggatctggtggagaaaaagtgcttagcaaaaaaatatactcacctct cctgcgataaagtcttctgccagccatggcagagatgcattgagggcacctgtgtttgtaaa ctaccgtatcagtgcccaaagaatggcactgcagtgtgtgcaactaacaggagaagcttccc aacatactgtcaacaaaagagtttggaatgtcttcatccagggacaaagtttttaaataacg gaacatgcacagccgaaggaaagtttagtgtttccttgaagcatggaaatacagattcagag ggaatagttgaagtaaaacttgtggaccaagataagacaatgttcatatgcaaaagcagctg gagcatgagggaagccaacgtggcctgccttgaccttgggtttcaacaaggtgctgatactc aaagaaggtttaagttgtctgatctctctataaattccactgaatgtctacatgtgcattgc cgaggattagagaccagtttggctgaatgtacttttactaagagaagaactatgggttacca ggatttcgctgatgtggtttgttatacacagaaagcagattctccaatggatgacttctttc agtgtgtgaatgggaaatacatttctcagatgaaagcctgtgatggtatcaatgattgtgga gaccaaagtgatgaactgtgttgtaaagcatgccaaggcaaaggcttccattgcaaatcggg tgtttgcattccaagccagtatcaatgcaatggtgaggtggactgcattacaggggaagatg aagttggctgtgcaggctttgcatctgtgactcaagaagaaacagaaattttgactgctgac atggatgcagaaagaagacggataaaatcattattacctaaactatcttgtggagttaaaaa cagaatgcacattcgaaggaaacgaattgtgggaggaaagcgagcacaactgggagacctcc catggcaggtggcaattaaggatgccagtggaatcacctgtgggggaatttatattggtggc tgttggattctgactgctgcacattgtctcagagccagtaaaactcatcgttaccaaatatg gacaacagtagtagactggatacaccccgaccttaaacgtatagtaattgaatacgtggata gaattattttccatgaaaactacaatgcaggcacttaccaaaatgacatcgctttgattgaa atgaaaaaagacggaaacaaaaaagattgtgagctgcctcgttccatccctgcctgtgtccc ctggtctccttacctattccaacctaatgatacatgcatcgtttctggctggggacgagaaa aagataacgaaagagtcttttcacttcagtggggtgaagttaaactaataagcaactgctct aagttttacggaaatcgtttctatgaaaaagaaatggaatgtgcaggtacatatgatggttc catcgatgcctgtaaaggggactctggaggccccttagtctgtatggatgccaacaatgtga cttatgtctggggtgttgtgagttggggggaaaactgtggaaaaccagagttcccaggtgtt tacaccaaagtggccaattattttgactggattagctaccatgtaggaaggccttttatttc tcagtacaatgtataa Example CFI nucleotide sequence (wild-type) (SEQ ID NO: 34) In some embodiments, the protein-coding sequence comprises or consists of a nucleotide sequence which is at least 70% identical to SEQ ID NO: 35. Suitably, the protein-coding sequence 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: 35. In some embodiments, the protein-coding sequence comprises or consists of the nucleotide sequence of SEQ ID NO: 35. In some embodiments, the protein-coding sequence consists of a nucleotide sequence which is at least 70% identical to SEQ ID NO: 35. Suitably, the protein-coding sequence 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: 35. In preferred embodiments, the protein-coding sequence consists of the nucleotide sequence of SEQ ID NO: 35. atgaagctgctgcatgtgttcctgctgttcctgtgcttccacctgagattctgcaaggtgac ctacaccagccaggaggacctggtggagaagaagtgcctggccaagaagtacacccacctga gctgtgacaaggtgttctgccagccctggcagctgtgcattgagggcacctgtgtgtgcaag ctgccctaccagtgccccaagaatggcacagctgtgtgtgccaccaacagaaggagcttccc cacctactgccagcagaagagcctggagtgcctgcaccctggcaccaagttcctgaacaatg gcacctgcacagctgagggcaagttcagtgtgagcctgaagcatggcaacacagacagtgag ggcattgtggaggtgaagctggtggaccaggacaagaccatgttcatctgcaagagcagttg gagcatgagagaggccaatgtggcctgcctggacctgggcttccagcaaggagctgacaccc agagaaggttcaagctgagtgacctgagcatcaacagcacagagtgcctgcatgtgcactgc agaggcctggagaccagcctggctgagtgcaccttcaccaagagaaggaccatgggctacca ggactttgctgatgtggtttgctacacccagaaggctgacagccccatggatgacttcttcc agtgtgtgaatggcaagtacatcagccagatgaaggcctgtgatggcatcaatgactgtgga gaccagagtgatgagctgtgctgcaaggcctgccagggcaagggcttccactgcaagagtgg agtgtgcatccccagccagtaccagtgcaatggagaggtggactgcatcacaggagaggatg aggtgggctgtgctggctttgccagtgtgacccaggaggagacagagatcctgacagctgac atggatgctgagagaaggagaatcaagagcctgctgcccaagctgagctgtggagtgaagaa cagaatgcacatcagaaggaagagaattgtgggaggcaagagagcccagctgggagacctgc cctggcaggtggccatcaaggatgccagtggcatcacctgtggaggaatctacattggaggc tgctggattctgacagctgcccactgcctgtatgccagcaagacccacagataccagatctg gaccacagtggttgactggattcaccctgacctgaagagaattgtgattgagtatgtggaca gaatcattttccatgagaactacaatgctggcacctaccagaatgacattgccctgattgag atgaagaaggatggcaacaagaaagactgtgagctgcccagaagcatccctgcctgtgtgcc ctggagcccctacctgttccagcccaatgacacctgtattgtcagtggatggggcagagaga aggacaatgagagagtgttcagcctgcagtggggagaggtgaagctgatcagcaactgcagc aagttctatggcaacagattctatgagaaggagatggagtgtgctggcacctatgatggcag cattgatgcctgcaagggagacagtggaggccccctggtgtgcatggatgccaacaatgtga cctatgtgtggggagtggttagctggggagagaactgtggcaagcctgagttccctggagtg tacaccaaggtggccaactactttgactggatcagctaccatgtgggcagacccttcatcag ccagtacaatgtgtaa Example CFI nucleotide sequence (mutant) (SEQ ID NO: 35) CFH In some embodiments, the protein-coding sequence encodes CFH. Complement factor H (CFH) regulates complement activation on self cells and surfaces. CFH competes for binding of complement factor B (CFB) to C3b, acts as a cofactor for CFI- catalysed proteolytic cleavage of C3b, and accelerates the irreversible dissociation of C3bBb and C3b2Bb into their separate components. Thus, CFH not only inhibits formation of the convertases but it also shortens the lifespan of any convertase complex that forms. CFH is a large (155 kDa) soluble glycoprotein. CFH is composed from a total of 20 domains, each containing approximately 60 amino acid residues and termed complement control protein modules (CCPs) or short consensus repeats that are joined by short linkers consisting of 3–8 residues. The CCP modules are numbered from 1–20 (from the N-terminus of the protein): CCPs 1–4 and CCPs 19–20 engage with C3b while CCPs 7 and CCPs 19–20 bind to GAGs and sialic acid. CFH is encoded by the CFH gene. The CFH gene is conserved in humans, chimpanzees, Rhesus monkeys, dogs, cows, and rats. In preferred embodiments, the CFH is a human CFH. A human CFH may consist of a polypeptide sequence of UniProtKB accession P08603. In some embodiments, the CFH comprises or consists of an amino acid sequence which is at least 70% identical to SEQ ID NO: 36. Suitably, the CFH 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: 36. In some embodiments, the CFH comprises or consists of the amino acid sequence of SEQ ID NO: 36. In some embodiments, the CFH consists of an amino acid sequence which is at least 70% identical to SEQ ID NO: 36. Suitably, the CFH 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: 36. In some embodiments, the CFH consists of the amino acid sequence of SEQ ID NO: 36. MRLLAKIICLMLWAICVAEDCNELPPRRNTEILTGSWSDQTYPEGTQAIYKCRPGYRSLGNV IMVCRKGEWVALNPLRKCQKRPCGHPGDTPFGTFTLTGGNVFEYGVKAVYTCNEGYQLLGEI NYRECDTDGWTNDIPICEVVKCLPVTAPENGKIVSSAMEPDREYHFGQAVRFVCNSGYKIEG DEEMHCSDDGFWSKEKPKCVEISCKSPDVINGSPISQKIIYKENERFQYKCNMGYEYSERGD AVCTESGWRPLPSCEEKSCDNPYIPNGDYSPLRIKHRTGDEITYQCRNGFYPATRGNTAKCT STGWIPAPRCTLKPCDYPDIKHGGLYHENMRRPYFPVAVGKYYSYYCDEHFETPSGSYWDHI HCTQDGWSPAVPCLRKCYFPYLENGYNQNYGRKFVQGKSIDVACHPGYALPKAQTTVTCMEN GWSPTPRCIRVKTCSKSSIDIENGFISESQYTYALKEKAKYQCKLGYVTADGETSGSITCGK DGWSAQPTCIKSCDIPVFMNARTKNDFTWFKLNDTLDYECHDGYESNTGSTTGSIVCGYNGW SDLPICYERECELPKIDVHLVPDRKKDQYKVGEVLKFSCKPGFTIVGPNSVQCYHFGLSPDL PICKEQVQSCGPPPELLNGNVKEKTKEEYGHSEVVEYYCNPRFLMKGPNKIQCVDGEWTTLP VCIVEESTCGDIPELEHGWAQLSSPPYYYGDSVEFNCSESFTMIGHRSITCIHGVWTQLPQC VAIDKLKKCKSSNLIILEEHLKNKKEFDHNSNIRYRCRGKEGWIHTVCINGRWDPEVNCSMA QIQLCPPPPQIPNSHNMTTTLNYRDGEKVSVLCQENYLIQEGEEITCKDGRWQSIPLCVEKI PCSQPPQIEHGTINSSRSSQESYAHGTKLSYTCEGGFRISEENETTCYMGKWSSPPQCEGLP CKSPPEISHGVVAHMSDSYQYGEEVTYKCFEGFGIDGPAIAKCLGEKWSHPPSCIKTDCLSL PSFENAIPMGEKKDVYKAGEQVTYTCATYYKMDGASNVTCINSRWTGRPTCRDTSCVNPPTV QNAYIVSRQMSKYPSGERVRYQCRSPYEMFGDEEVMCLNGNWTEPPQCKDSTGKCGPPPPID NGDITSFPLSVYAPASSVEYQCQNLYQLEGNKRITCRNGQWSEPPKCLHPCVISREIMENYN IALRWTAKQKLYSRTGESVEFVCKRGYRLSSRSHTLRTTCWDGKLEYPTCAKR Example CFH amino acid sequence (SEQ ID NO: 36) In preferred embodiments, the protein-coding sequence encodes a full-length wild-type CFH. In more preferred embodiments, the protein-coding sequence encodes a full-length wild-type human CFH. Although it is preferred that the protein-coding sequence encodes a full-length wild-type CFH, the protein-coding sequence may alternatively encode a fragment and / or variant of CFH that retains CFH activity. For example, a fragment and / or variant of CFH that is capable of binding C3b and / or C3d; and / or acting as a cofactor for the CFI-catalysed proteolytic cleavage of C3b; and / or increasing the irreversible dissociation of C3bBb and C3b2Bb into their separate components. The fragment and / or variant of CFH may retain at least 50%, 60%, 70%, 80%, 90%, 95% or 100% of the activity of native CFH. The activity of the fragment and / or variant of CFH and native CFH may be determined using any suitable method known to those of skill in the art. A person skilled in the art would be able to generate fragments and / or variants of CFH using conservative substitutions, based on the known structural and functional features of CFH (see e.g. Zipfel, P.F., et al., 2002. Biochemical Society Transactions, 30(6), pp.971-978), and / or based on known variants (see e.g. NCBI Gene ID: 3075 and NCBI HomoloGene: 20086). Suitably, a fragment and / or variant of CFH comprises CCPs 1–4, 7 and CCPs 19–20. Example nucleotide sequences encoding CFH are provided by SEQ ID NOs: 37 and 80. In some embodiments, the protein-coding sequence comprises or consists of a nucleotide sequence which is at least 70% identical to SEQ ID NO: 37. Suitably, the protein-coding sequence 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: 37. In some embodiments, the protein-coding sequence comprises or consists of the nucleotide sequence of SEQ ID NO: 37. In some embodiments, the protein-coding sequence consists of a nucleotide sequence which is at least 70% identical to SEQ ID NO: 37. Suitably, the protein-coding sequence 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: 37. In preferred embodiments, the protein-coding sequence consists of the nucleotide sequence of SEQ ID NO: 37. atgaggctgctggcaaagattatctgtctcatgctgtgggctatttgcgtggccgaggactg caacgagctgcctccaaggagaaataccgagatcctgaccggaagctggagcgaccagacct accccgagggcacccaggccatctataagtgccggcccggctacaggtccctggggaacgtg atcatggtgtgccggaagggagagtgggtggccctgaaccctctgagaaaatgccagaagag gccctgcggccaccccggagatactccctttgggaccttcacactgaccggcggcaacgtct tcgagtacggcgtgaaagccgtgtatacttgcaatgaaggctatcagctgctgggagaaatt aactacagggagtgcgacaccgatggctggaccaatgacattcccatctgcgaagtggtgaa gtgcctgcctgtgaccgctcccgaaaacggcaaaattgtgtccagcgccatggagcccgacc gggagtatcacttcggacaggccgtgaggttcgtgtgcaattccggatataagatcgagggg gacgaagagatgcactgctccgacgatggcttctggtccaaggagaagcccaagtgtgtgga gatcagctgtaagagcccagacgtgatcaacggctcccctatctcacagaagattatctata aagagaatgaacgctttcagtacaagtgtaacatgggctatgagtattccgagaggggcgat gccgtgtgtaccgagagcggatggaggcccctgccttcctgcgaggagaagtcatgtgacaa tccttacatccctaacggcgattactctcccctgcgcatcaagcacagaactggggatgaga ttacctatcagtgccggaatggcttctaccctgccacaagaggcaacactgcaaagtgtaca tctacaggctggatccccgcccccagatgcaccctgaagccctgcgactatcccgacatcaa acacggaggattgtaccacgagaacatgcgtcggccttatttccccgtggccgtgggaaagt actactcctactattgcgacgagcactttgagactcctagcggaagctattgggatcatatc cactgcacccaggacggatggtctccagccgtgccttgtctgagaaagtgctactttccata cctcgagaatggctacaatcagaatcatggcagaaagttcgtgcagggaaagagcattgacg ttgcctgccaccctggctacgccctgcctaaggcccagaccacagtgacctgtatggagaat ggctggagccccaccccaaggtgcatcagagtcaagacatgctctaagtcctccatcgacat cgagaacgggtttatctctgaatcccagtatacatatgccctcaaggaaaaagccaagtatc agtgcaagctcggctacgtgaccgctgacggcgaaacaagcggcagtatcacatgtggcaag gatggctggtcagcccagcctacctgtatcaagagctgcgacatcccagtgtttatgaacgc caggaccaaaaacgacttcacatggttcaaactgaacgacacactggactacgagtgtcacg acggctatgagtctaacaccggctccactacaggaagcatcgtgtgtggttataacggatgg tccgatctgcccatctgctatgagagagagtgcgagctgcccaagatcgatgtccacctagt gccagacagaaagaaggatcagtacaaggtcggcgaggtgctgaagttcagttgtaaacccg gcttcactattgtggggcccaactccgtgcaatgctatcactttggcctgagccctgacctg cccatctgtaaggagcaggtgcagagctgcggccctccccccgagctgctgaatgggaatgt gaaggagaagaccaaggaggaatacggccactccgaggtggtggagtattactgcaaccctc gctttctcatgaaaggccccaacaagatccagtgcgtcgatggcgagtggaccaccctgccc gtgtgtattgtcgaggagagtacctgcggcgatatccctgaactggagcacgggtgggccca gctgtcctcccccccatactactacggggactccgtggagttcaactgcagcgagtccttca ccatgattggacatcggagtatcacctgtatccacggcgtatggactcagctgccacagtgc gtggccatcgataagctgaagaaatgtaagagcagtaacctgattatcctcgaagaacacct gaagaacaagaaggaatttgatcataacagcaatatcaggtacagatgcaggggaaaggagg gatggattcacacagtgtgcatcaatggccgctgggaccctgaggtcaattgcagcatggcc cagatccagctgtgtcctccaccaccccagatccccaatagccataacatgaccacaaccct gaattacagagatggcgaaaaggtgagcgtgctgtgccaggagaactacctgatccaggagg gcgaggaaataacctgtaaggacggacggtggcagagcatccccctgtgcgtggagaagatt ccctgctcacagcccccacagatcgagcacggaacaatcaatagctccaggagcagccagga gtcttatgcccacggcaccaagctgagctacacctgcgaggggggcttccggatcagcgagg aaaacgaaacaacatgctacatgggcaaatggagcagtcctcctcagtgtgagggcctgcca tgtaaaagcccacctgagatcagtcacggcgtggtcgctcacatgagcgactcctaccagta tggcgaggaggtgacatataagtgcttcgagggctttggcatcgacggccccgctattgcca agtgcctgggagagaaatggtcacacccaccttcttgcatcaagacagactgcctgagcctc ccctctttcgagaatgcaatccccatgggcgaaaaaaaggatgtgtacaaggccggcgagca ggtgacctatacctgcgccacctactacaaaatggacggtgcctccaatgtgacctgtatca attccaggtggactggcagaccaacctgccgggacactagctgcgtgaatccccccactgtg cagaatgcctatatcgtgagcagacagatgagcaagtacccatctggtgagcgggtgaggta ccagtgccggtccccatatgagatgtttggggacgaggaggtgatgtgtcttaacggaaact ggactgaacctccccagtgtaaggacagtaccggcaagtgtgggccaccccctcccatcgac aacggcgatattacatcctttccactgtcagtgtacgcccccgccagctccgtggagtacca gtgtcagaatctgtaccagctggagggcaacaagaggatcacctgtagaaacggccagtgga gcgagccaccaaagtgcctgcatccctgtgtgatcagcagggagatcatggagaattacaac atcgcactgcggtggaccgccaagcagaaactgtactcccgcacaggggagtccgtggagtt tgtctgtaaacggggctacagactgagttccagaagccacaccctgagaaccacctgttggg atgggaagctggaatatcccacctgtgcaaagagatga Example CFH nucleotide sequence (codon-optimised) (SEQ ID NO: 37) In some embodiments, the protein-coding sequence comprises or consists of a nucleotide sequence which is at least 70% identical to SEQ ID NO: 80 Suitably, the protein-coding sequence 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: 80. In some embodiments, the protein-coding sequence comprises or consists of the nucleotide sequence of SEQ ID NO: 80. In some embodiments, the protein-coding sequence consists of a nucleotide sequence which is at least 70% identical to SEQ ID NO: 80. Suitably, the protein-coding sequence 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: 80. In some embodiments, the protein-coding sequence consists of the nucleotide sequence of SEQ ID NO: 80. atgagacttctagcaaagattatttgccttatgttatgggctatttgtgtagcagaagattg caatgaacttcctccaagaagaaatacagaaattctgacaggttcctggtctgaccaaacat atccagaaggcacccaggctatctataaatgccgccctggatatagatctcttggaaatgta ataatggtatgcaggaagggagaatgggttgctcttaatccattaaggaaatgtcagaaaag gccctgtggacatcctggagatactccttttggtacttttacccttacaggaggaaatgtgt ttgaatatggtgtaaaagctgtgtatacatgtaatgaggggtatcaattgctaggtgagatt aattaccgtgaatgtgacacagatggatggaccaatgatattcctatatgtgaagttgtgaa gtgtttaccagtgacagcaccagagaatggaaaaattgtcagtagtgcaatggaaccagatc gggaataccattttggacaagcagtacggtttgtatgtaactcaggctacaagattgaagga gatgaagaaatgcattgttcagacgatggtttttggagtaaagagaaaccaaagtgtgtgga aatttcatgcaaatccccagatgttataaatggatctcctatatctcagaagattatttata aggagaatgaacgatttcaatataaatgtaacatgggttatgaatacagtgaaagaggagat gctgtatgcactgaatctggatggcgtccgttgccttcatgtgaagaaaaatcatgtgataa tccttatattccaaatggtgactactcacctttaaggattaaacacagaactggagatgaaa tcacgtaccagtgtagaaatggtttttatcctgcaacccggggaaatacagcaaaatgcaca agtactggctggatacctgctccgagatgtaccttgaaaccttgtgattatccagacattaa acatggaggtctatatcatgagaatatgcgtagaccatactttccagtagctgtaggaaaat attactcctattactgtgatgaacattttgagactccgtcaggaagttactgggatcacatt cattgcacacaagatggatggtcgccagcagtaccatgcctcagaaaatgttattttcctta tttggaaaatggatataatcaaaatcatggaagaaagtttgtacagggtaaatctatagacg ttgcctgccatcctggctacgctcttccaaaagcgcagaccacagttacatgtatggagaat ggctggtctcctactcccagatgcatccgtgtcaaaacatgttccaaatcaagtatagatat tgagaatgggtttatttctgaatctcagtatacatatgccttaaaagaaaaagcgaaatatc aatgcaaactaggatatgtaacagcagatggtgaaacatcaggatcaattacatgtgggaaa gatggatggtcagctcaacccacgtgcattaaatcttgtgatatcccagtatttatgaatgc cagaactaaaaatgacttcacatggtttaagctgaatgacacattggactatgaatgccatg atggttatgaaagcaatactggaagcaccactggttccatagtgtgtggttacaatggttgg tctgatttacccatatgttatgaaagagaatgcgaacttcctaaaatagatgtacacttagt tcctgatcgcaagaaagaccagtataaagttggagaggtgttgaaattctcctgcaaaccag gatttacaatagttggacctaattccgttcagtgctaccactttggattgtctcctgacctc ccaatatgtaaagagcaagtacaatcatgtggtccacctcctgaactcctcaatgggaatgt taaggaaaaaacgaaagaagaatatggacacagtgaagtggtggaatattattgcaatccta gatttctaatgaagggacctaataaaattcaatgtgttgatggagagtggacaactttacca gtgtgtattgtggaggagagtacctgtggagatatacctgaacttgaacatggctgggccca gctttcttcccctccttattactatggagattcagtggaattcaattgctcagaatcattta caatgattggacacagatcaattacgtgtattcatggagtatggacccaacttccccagtgt gtggcaatagataaacttaagaagtgcaaatcatcaaatttaattatacttgaggaacattt aaaaaacaagaaggaattcgatcataattctaacataaggtacagatgtagaggaaaagaag gatggatacacacagtctgcataaatggaagatgggatccagaagtgaactgctcaatggca caaatacaattatgcccacctccacctcagattcccaattctcacaatatgacaaccacact gaattatcgggatggagaaaaagtatctgttctttgccaagaaaattatctaattcaggaag gagaagaaattacatgcaaagatggaagatggcagtcaataccactctgtgttgaaaaaatt ccatgttcacaaccacctcagatagaacacggaaccattaattcatccaggtcttcacaaga aagttatgcacatgggactaaattgagttatacttgtgagggtggtttcaggatatctgaag aaaatgaaacaacatgctacatgggaaaatggagttctccacctcagtgtgaaggccttcct tgtaaatctccacctgagatttctcatggtgttgtagctcacatgtcagacagttatcagta tggagaagaagttacgtacaaatgttttgaaggttttggaattgatgggcctgcaattgcaa aatgcttaggagaaaaatggtctcaccctccatcatgcataaaaacagattgtctcagttta cctagctttgaaaatgccatacccatgggagagaagaaggatgtgtataaggcgggtgagca agtgacttacacttgtgcaacatattacaaaatggatggagccagtaatgtaacatgcatta atagcagatggacaggaaggccaacatgcagagacacctcctgtgtgaatccgcccacagta caaaatgcttatatagtgtcgagacagatgagtaaatatccatctggtgagagagtacgtta tcaatgtaggagcccttatgaaatgtttggggatgaagaagtgatgtgtttaaatggaaact ggacggaaccacctcaatgcaaagattctacaggaaaatgtgggccccctccacctattgac aatggggacattacttcattcccgttgtcagtatatgctccagcttcatcagttgagtacca atgccagaacttgtatcaacttgagggtaacaagcgaataacatgtagaaatggacaatggt cagaaccaccaaaatgcttacatccgtgtgtaatatcccgagaaattatggaaaattataac atagcattaaggtggacagccaaacagaagctttattcgagaacaggtgaatcagttgaatt tgtgtgtaaacggggatatcgtctttcatcacgttctcacacattgcgaacaacatgttggg atgggaaactggagtatccaacttgtgcaaaaagatag Example CFH nucleotide sequence (wild-type) (SEQ ID NO: 80) FHL-1 In some embodiments, the protein-coding sequence encodes FHL-1. (FHL-1) is a CFH gene splice variant, which is almost identical to the N-terminal 7 domains of CFH (CCPs 1-7). In some embodiments, the FHL-1 comprises or consists of an amino acid sequence which is at least 70% identical to SEQ ID NO: 38. Suitably, the FHL-1 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: 38. In some embodiments, the FHL-1 comprises or consists of the amino acid sequence of SEQ ID NO: 38. In some embodiments, the FHL-1 consists of an amino acid sequence which is at least 70% identical to SEQ ID NO: 38. Suitably, the FHL-1 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: 38. In some embodiments, the FHL-1 consists of the amino acid sequence of SEQ ID NO: 38. MRLLAKIICLMLWAICVAEDCNELPPRRNTEILTGSWSDQTYPEGTQAIYKCRPGYRSLGNV IMVCRKGEWVALNPLRKCQKRPCGHPGDTPFGTFTLTGGNVFEYGVKAVYTCNEGYQLLGEI NYRECDTDGWTNDIPICEVVKCLPVTAPENGKIVSSAMEPDREYHFGQAVRFVCNSGYKIEG DEEMHCSDDGFWSKEKPKCVEISCKSPDVINGSPISQKIIYKENERFQYKCNMGYEYSERGD AVCTESGWRPLPSCEEKSCDNPYIPNGDYSPLRIKHRTGDEITYQCRNGFYPATRGNTAKCT STGWIPAPRCTLKPCDYPDIKHGGLYHENMRRPYFPVAVGKYYSYYCDEHFETPSGSYWDHI HCTQDGWSPAVPCLRKCYFPYLENGYNQNHGRKFVQGKSIDVACHPGYALPKAQTTVTCMEN GWSPTPRCIRVSFTL Example FHL1 polypeptide (SEQ ID NO: 38) In preferred embodiments, the protein-coding sequence encodes a full-length wild-type FHL- 1. In more preferred embodiments, the protein-coding sequence encodes a full-length wild- type human FHL-1. Although it is preferred that the protein-coding sequence encodes a full-length wild-type FHL- 1, the protein-coding sequence may alternatively encode a fragment and / or variant of FHL-1 that retains FHL-1 activity. For example, a fragment and / or variant of FHL-1 that is capable of binding C3b and / or C3d. The fragment and / or variant of FHL-1 may retain at least 50%, 60%, 70%, 80%, 90%, 95% or 100% of the activity of native FHL-1. The activity of the fragment and / or variant of FHL-1 and native FHL-1 may be determined using any suitable method known to those of skill in the art. A person skilled in the art would be able to generate fragments and / or variants of FHL-1 using conservative substitutions, based on the known structural and functional features of FHL-1 (see e.g. Zipfel, P.F., et al., 2002. Biochemical Society Transactions, 30(6), pp.971-978), and / or based on known variants of CFH (see e.g. NCBI Gene ID: 3075 and NCBI HomoloGene: 20086). Suitably, a fragment and / or variant of FHL-1 comprises CCPs 1-7. Example nucleotide sequences encoding FHL-1 are provided by SEQ ID NOs: 39 and 81. In some embodiments, the protein-coding sequence comprises or consists of a nucleotide sequence which is at least 70% identical to SEQ ID NO: 39. Suitably, the protein-coding sequence 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: 39. In some embodiments, the protein-coding sequence comprises or consists of the nucleotide sequence of SEQ ID NO: 39. In some embodiments, the protein-coding sequence consists of a nucleotide sequence which is at least 70% identical to SEQ ID NO: 39. Suitably, the protein-coding sequence 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: 39. In preferred embodiments, the protein-coding sequence consists of the nucleotide sequence of SEQ ID NO: 39. atgcggctgctggccaaaatcatctgtctgatgctgtgggccatctgtgtggccgaggattg caacgagctgccccctagacgcaatacagagatcctgacaggcagctggtccgaccagacat accctgagggaacccaggccatctacaagtgcagaccaggatatcggtccctgggaaatgtg ataatggtgtgtagaaagggagagtgggtggctctgaaccctctgaggaaatgccagaagcg cccatgcggccaccccggcgatacccccttcggcaccttcacactgaccggcggcaatgtgt ttgagtatggcgtgaaggccgtgtacacctgcaacgagggctaccagctgctgggtgagatt aactaccgcgagtgtgataccgacggctggaccaacgacatccccatctgtgaagtggtgaa gtgtctgcccgtgaccgcaccagagaatggcaaaatcgtgagttctgccatggagcctgata gggagtaccactttggccaggccgtgcgctttgtgtgtaattctggctacaagatcgagggc gacgaggagatgcattgctctgacgatggcttctggtcaaaggaaaagcccaaatgcgtgga gattagctgtaagtccccagacgtcatcaacggctcccctatctctcagaagatcatttaca aggagaatgaacggtttcagtataaatgcaacatgggctacgagtactccgagcggggcgat gccgtgtgtaccgagtcagggtggcgaccactccctagttgtgaagagaagagctgcgacaa tccctacatccccaacggcgactactctccactgaggatcaagcacaggacaggcgacgaga tcacctaccagtgccgcaacgggttttaccctgccacaaggggcaatactgccaagtgcacc agcacagggtggattcctgccccccggtgtacactgaagccatgcgattacccagatatcaa acatgggggcctgtaccatgagaatatgaggcggccatactttcccgtggccgtgggcaagt actactcctactattgcgacgagcactttgagacaccctccggctcctactgggaccatatc cactgtacccaggatggctggtcccctgccgtgccatgtctgagaaaatgctacttccccta tctggagaacgggtacaaccagaaccacgggaggaagttcgttcaggggaagtccattgacg tggcctgccatcccggctacgccctgcccaaggcccagactactgtgacctgcatggagaat ggttggagccccaccccccggtgtatccgggtgagctttacccgttga Example FHL-1 nucleotide sequence (codon-optimised) (SEQ ID NO: 39) In some embodiments, the protein-coding sequence comprises or consists of a nucleotide sequence which is at least 70% identical to SEQ ID NO: 81. Suitably, the protein-coding sequence 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: 81. In some embodiments, the protein-coding sequence comprises or consists of the nucleotide sequence of SEQ ID NO: 81. In some embodiments, the protein-coding sequence consists of a nucleotide sequence which is at least 70% identical to SEQ ID NO: 81. Suitably, the protein-coding sequence 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: 81. In some embodiments, the protein-coding sequence consists of the nucleotide sequence of SEQ ID NO: 81. atgagacttctagcaaagattatttgccttatgttatgggctatttgtgtagcagaagattg caatgaacttcctccaagaagaaatacagaaattctgacaggttcctggtctgaccaaacat atccagaaggcacccaggctatctataaatgccgccctggatatagatctcttggaaatgta ataatggtatgcaggaagggagaatgggttgctcttaatccattaaggaaatgtcagaaaag gccctgtggacatcctggagatactccttttggtacttttacccttacaggaggaaatgtgt ttgaatatggtgtaaaagctgtgtatacatgtaatgaggggtatcaattgctaggtgagatt aattaccgtgaatgtgacacagatggatggaccaatgatattcctatatgtgaagttgtgaa gtgtttaccagtgacagcaccagagaatggaaaaattgtcagtagtgcaatggaaccagatc gggaataccattttggacaagcagtacggtttgtatgtaactcaggctacaagattgaagga gatgaagaaatgcattgttcagacgatggtttttggagtaaagagaaaccaaagtgtgtgga aatttcatgcaaatccccagatgttataaatggatctcctatatctcagaagattatttata aggagaatgaacgatttcaatataaatgtaacatgggttatgaatacagtgaaagaggagat gctgtatgcactgaatctggatggcgtccgttgccttcatgtgaagaaaaatcatgtgataa tccttatattccaaatggtgactactcacctttaaggattaaacacagaactggagatgaaa tcacgtaccagtgtagaaatggtttttatcctgcaacccggggaaatacagcaaaatgcaca agtactggctggatacctgctccgagatgtaccttgaaaccttgtgattatccagacattaa acatggaggtctatatcatgagaatatgcgtagaccatactttccagtagctgtaggaaaat attactcctattactgtgatgaacattttgagactccgtcaggaagttactgggatcacatt cattgcacacaagatggatggtcgccagcagtaccatgcctcagaaaatgttattttcctta tttggaaaatggatataatcaaaatcatggaagaaagtttgtacagggtaaatctatagacg ttgcctgccatcctggctacgctcttccaaaagcgcagaccacagttacatgtatggagaat ggctggtctcctactcccagatgcatccgtgtcagctttaccctctga Example FHL-1 nucleotide sequence (wild-type) (SEQ ID NO: 81) Bicistronic complement inhibitor coding sequences In some embodiments, the one or more protein-coding sequence encodes CFI and FHL-1. The protein-coding sequence may encode two or more inhibitors of the complement system. Suitably, a first protein-coding sequence encoding a complement inhibitor is linked to a second protein-coding sequence encoding another complement inhibitor by a nucleotide sequence encoding a 2A self-cleaving peptide or an IRES element. These elements allow for the efficient translation of multiple genes from a single transcript (see e.g. Liu, Z., et al., 2017. Scientific reports, 7(1), p.2193; and Renaud-Gabardos, E., et al., 2015. World journal of experimental medicine, 5(1), pp.11-20). In some embodiments, the protein-coding sequence encodes CFI and FHL-1, linked by a nucleotide sequence encoding a 2A self-cleaving peptide. 2A self-cleaving peptides are a class of 18–22 aa-long peptides, which can induce ribosomal skipping during translation of a protein in a cell. Suitable 2A self-cleaving peptides include T2A, P2A, E2A and F2A, or variants thereof. In some embodiments, a 2A self-cleaving peptide has at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% identity to any of SEQ ID NOs: 40-43. In some embodiments, a 2A self-cleaving peptide comprises or consists of the amino acid sequence any of SEQ ID NOs: 40-43. ATNFSLLKQAGDVEENPGP Example P2A peptide sequence (SEQ ID NO: 40) EGRGSLLTCGDVEENPGP Example T2A peptide sequence (SEQ ID NO: 41) QCTNYALLKLAGDVESNPGP Example E2A peptide sequence (SEQ ID NO: 42) VKQTLNFDLLKLAGDVESNPGP Example F2A peptide sequence (SEQ ID NO: 43) In some embodiments, the 2A self-cleaving peptide is a P2A self-cleaving peptide. A P2A self- cleaving peptide may have at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% identity to SEQ ID NO: 44. In some embodiments, a P2A self- cleaving peptide comprises or consists of the amino acid sequence of SEQ ID NO: 44. GSGATNFSLLKQAGDVEENPGP Example P2A self-cleaving peptide (SEQ ID NO: 44) In some embodiments, the nucleotide encoding a 2A self-cleaving peptide comprises or consists of a nucleotide sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identity, or 100% identity to SEQ ID NO: 45. In some embodiments, the nucleotide encoding a 2A self- cleaving peptide comprises or consists of the nucleotide sequence of SEQ ID NO: 45. ggaagcggagctactaacttcagcctgctgaagcaggctggcgacgtggaggagaaccctgg acct Example P2A self-cleaving peptide nucleotide (SEQ ID NO: 45) In some embodiments, the protein-coding sequence encodes from 5’ to 3’: CFI; a 2A self- cleaving peptide; and FHL-1. In some embodiments, the protein-coding sequence encodes an amino acid sequence comprising or consisting of an amino acid sequence which is at least 70% identical to SEQ ID NO: 46. In some embodiments, the protein-coding sequence encodes an amino acid sequence comprising or consisting of an amino acid 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: 46. In some embodiments, the protein-coding sequence encodes an amino acid sequence comprising or consisting of the amino acid sequence of SEQ ID NO: 46. MKLLHVFLLFLCFHLRFCKVTYTSQEDLVEKKCLAKKYTHLSCDKVFCQPWQRCIEGTCVCK LPYQCPKNGTAVCATNRRSFPTYCQQKSLECLHPGTKFLNNGTCTAEGKFSVSLKHGNTDSE GIVEVKLVDQDKTMFICKSSWSMREANVACLDLGFQQGADTQRRFKLSDLSINSTECLHVHC RGLETSLAECTFTKRRTMGYQDFADVVCYTQKADSPMDDFFQCVNGKYISQMKACDGINDCG DQSDELCCKACQGKGFHCKSGVCIPSQYQCNGEVDCITGEDEVGCAGFASVTQEETEILTAD MDAERRRIKSLLPKLSCGVKNRMHIRRKRIVGGKRAQLGDLPWQVAIKDASGITCGGIYIGG CWILTAAHCLRASKTHRYQIWTTVVDWIHPDLKRIVIEYVDRIIFHENYNAGTYQNDIALIE MKKDGNKKDCELPRSIPACVPWSPYLFQPNDTCIVSGWGREKDNERVFSLQWGEVKLISNCS KFYGNRFYEKEMECAGTYDGSIDACKGDSGGPLVCMDANNVTYVWGVVSWGENCGKPEFPGV YTKVANYFDWISYHVGRPFISQYNVDYKDDDDKGSGATNFSLLKQAGDVEENPGPMRLLAKI ICLMLWAICVAEDCNELPPRRNTEILTGSWSDQTYPEGTQAIYKCRPGYRSLGNVIMVCRKG EWVALNPLRKCQKRPCGHPGDTPFGTFTLTGGNVFEYGVKAVYTCNEGYQLLGEINYRECDT DGWTNDIPICEVVKCLPVTAPENGKIVSSAMEPDREYHFGQAVRFVCNSGYKIEGDEEMHCS DDGFWSKEKPKCVEISCKSPDVINGSPISQKIIYKENERFQYKCNMGYEYSERGDAVCTESG WRPLPSCEEKSCDNPYIPNGDYSPLRIKHRTGDEITYQCRNGFYPATRGNTAKCTSTGWIPA PRCTLKPCDYPDIKHGGLYHENMRRPYFPVAVGKYYSYYCDEHFETPSGSYWDHIHCTQDGW SPAVPCLRKCYFPYLENGYNQNHGRKFVQGKSIDVACHPGYALPKAQTTVTCMENGWSPTPR CIRVSFTLYPYDVPDYA Example CFI-P2A-FHL1 amino acid sequence (SEQ ID NO: 46) In some embodiments, the protein-coding sequence comprises or consists of a nucleotide sequence which is at least 70% identical to SEQ ID NO: 47. Suitably, the protein-coding sequence 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: 47. In some embodiments, the protein-coding sequence comprises or consists of the nucleotide sequence of SEQ ID NO: 47. atgaagctgctgcatgtgttcctgttgttcctgtgttttcacctgagattttgtaaggtgac ttataccagccaggaagacctggtagagaagaagtgcctggccaagaagtatactcacctgt cttgcgataaggtgttctgccagccttggcagcggtgcatcgagggcacctgtgtgtgcaag ctgccctatcagtgtcccaagaatgggaccgccgtgtgtgccaccaacagaaggagcttccc cacctattgccagcagaagagcctggagtgtctgcaccccggcaccaagttcctgaataatg gcacatgtaccgccgagggcaagttctcagtctccctgaagcatggcaacactgacagtgag ggcatcgtggaggtgaaactggtggaccaggacaagacaatgttcatctgtaagtcatcttg gtctatgcgggaggccaacgtggcctgcctggatctgggcttccagcagggggccgataccc agaggcgattcaagctgagcgatctgtctataaacagcaccgagtgcctgcacgtgcactgc aggggcctggaaacctctctggccgaatgcaccttcaccaagagacggactatgggctacca ggattttgccgatgtggtgtgctatacccagaaagccgactcccccatggacgacttcttcc aatgtgtcaatggaaagtacatcagtcagatgaaggcatgtgacggcattaacgattgtggc gatcagagcgatgagctgtgctgtaaggcctgccagggaaagggcttccactgcaaatccgg cgtgtgcatccctagccagtaccagtgtaatggcgaggtggactgtatcacaggagaggacg aagtgggatgcgctggattcgctagtgtgacccaggaggagaccgagatcctgaccgccgac atggatgccgagaggagacgtatcaagtccctgctgcctaagctgtcttgtggagtgaagaa taggatgcacatcagacgcaagagaatcgtcggcggcaagcgcgcccagctgggcgatctgc cctggcaagtggccattaaggacgcctccggcatcacatgtggaggaatatacataggcggg tgctggatcctgaccgccgcccactgcctgcgggcctctaaaactcataggtaccagatctg gacaaccgtggtggattggatccatcctgatctgaagagaatcgtgatcgagtacgtcgata ggattatctttcacgagaactataatgccgggacctaccagaatgacatcgctctcattgag atgaagaaggatggcaacaagaaggactgcgagctgcccaggagcattcccgcttgcgtgcc atggtccccatacctgttccagccaaacgacacctgcatcgtgagcggctggggcagagaaa aggacaacgagagagtgttctccctgcagtggggcgaagtgaagctgatttccaactgcagt aagttctacggcaaccgcttctatgagaaggagatggagtgtgccggcacatacgacggcag catcgacgcctgcaagggcgacagcggcggccccctggtgtgcatggacgccaacaacgtga cctatgtgtggggggtggtgtcctggggcgagaactgtggaaagccagagttccctggagtg tataccaaggtggccaactacttcgattggatcagctaccacgtcggcaggcccttcatcag ccagtacaacgttggaagcggagctactaacttcagcctgctgaagcaggctggcgacgtgg aggagaaccctggacctatgcggctgctggccaaaatcatctgtctgatgctgtgggccatc tgtgtggccgaggattgcaacgagctgccccctagacgcaatacagagatcctgacaggcag ctggtccgaccagacataccctgagggaacccaggccatctacaagtgcagaccaggatatc ggtccctgggaaatgtgataatggtgtgtagaaagggagagtgggtggctctgaaccctctg aggaaatgccagaagcgcccatgcggccaccccggcgatacccccttcggcaccttcacact gaccggcggcaatgtgtttgagtatggcgtgaaggccgtgtacacctgcaacgagggctacc agctgctgggtgagattaactaccgcgagtgtgataccgacggctggaccaacgacatcccc atctgtgaagtggtgaagtgtctgcccgtgaccgcaccagagaatggcaaaatcgtgagttc tgccatggagcctgatagggagtaccactttggccaggccgtgcgctttgtgtgtaattctg gctacaagatcgagggcgacgaggagatgcattgctctgacgatggcttctggtcaaaggaa aagcccaaatgcgtggagattagctgtaagtccccagacgtcatcaacggctcccctatctc tcagaagatcatttacaaggagaatgaacggtttcagtataaatgcaacatgggctacgagt actccgagcggggcgatgccgtgtgtaccgagtcagggtggcgaccactccctagttgtgaa gagaagagctgcgacaatccctacatccccaacggcgactactctccactgaggatcaagca caggacaggcgacgagatcacctaccagtgccgcaacgggttttaccctgccacaaggggca atactgccaagtgcaccagcacagggtggattcctgccccccggtgtacactgaagccatgc gattacccagatatcaaacatgggggcctgtaccatgagaatatgaggcggccatactttcc cgtggccgtgggcaagtactactcctactattgcgacgagcactttgagacaccctccggct cctactgggaccatatccactgtacccaggatggctggtcccctgccgtgccatgtctgaga aaatgctacttcccctatctggagaacgggtacaaccagaaccacgggaggaagttcgttca ggggaagtccattgacgtggcctgccatcccggctacgccctgcccaaggcccagactactg tgacctgcatggagaatggttggagccccaccccccggtgtatccgggtgagctttaccctg Example CFI-P2A-FHL1 nucleotide sequence (SEQ ID NO: 47) In some embodiments, the protein-coding sequence encodes from 5’ to 3’: FHL-1; a 2A self- cleaving peptide; and CFI. In some embodiments, the protein-coding sequence encodes an amino acid sequence comprising or consisting of an amino acid sequence which is at least 70% identical to SEQ ID NO: 48. In some embodiments, the protein-coding sequence encodes an amino acid sequence comprising or consisting of an amino acid 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: 48. In some embodiments, the protein-coding sequence encodes an amino acid sequence comprising or consisting of the amino acid sequence of SEQ ID NO: 48. MRLLAKIICLMLWAICVAEDCNELPPRRNTEILTGSWSDQTYPEGTQAIYKCRPGYRSLGNV IMVCRKGEWVALNPLRKCQKRPCGHPGDTPFGTFTLTGGNVFEYGVKAVYTCNEGYQLLGEI NYRECDTDGWTNDIPICEVVKCLPVTAPENGKIVSSAMEPDREYHFGQAVRFVCNSGYKIEG DEEMHCSDDGFWSKEKPKCVEISCKSPDVINGSPISQKIIYKENERFQYKCNMGYEYSERGD AVCTESGWRPLPSCEEKSCDNPYIPNGDYSPLRIKHRTGDEITYQCRNGFYPATRGNTAKCT STGWIPAPRCTLKPCDYPDIKHGGLYHENMRRPYFPVAVGKYYSYYCDEHFETPSGSYWDHI HCTQDGWSPAVPCLRKCYFPYLENGYNQNHGRKFVQGKSIDVACHPGYALPKAQTTVTCMEN GWSPTPRCIRVSFTLYPYDVPDYAGSGATNFSLLKQAGDVEENPGPMKLLHVFLLFLCFHLR FCKVTYTSQEDLVEKKCLAKKYTHLSCDKVFCQPWQRCIEGTCVCKLPYQCPKNGTAVCATN RRSFPTYCQQKSLECLHPGTKFLNNGTCTAEGKFSVSLKHGNTDSEGIVEVKLVDQDKTMFI CKSSWSMREANVACLDLGFQQGADTQRRFKLSDLSINSTECLHVHCRGLETSLAECTFTKRR TMGYQDFADVVCYTQKADSPMDDFFQCVNGKYISQMKACDGINDCGDQSDELCCKACQGKGF HCKSGVCIPSQYQCNGEVDCITGEDEVGCAGFASVTQEETEILTADMDAERRRIKSLLPKLS CGVKNRMHIRRKRIVGGKRAQLGDLPWQVAIKDASGITCGGIYIGGCWILTAAHCLRASKTH RYQIWTTVVDWIHPDLKRIVIEYVDRIIFHENYNAGTYQNDIALIEMKKDGNKKDCELPRSI PACVPWSPYLFQPNDTCIVSGWGREKDNERVFSLQWGEVKLISNCSKFYGNRFYEKEMECAG TYDGSIDACKGDSGGPLVCMDANNVTYVWGVVSWGENCGKPEFPGVYTKVANYFDWISYHVG RPFISQYNVDYKDDDDK Example FHL1-P2A-CFI amino acid sequence (SEQ ID NO: 48) In some embodiments, the protein-coding sequence comprises or consists of a nucleotide sequence which is at least 70% identical to SEQ ID NO: 49. Suitably, the protein-coding sequence 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: 49. In some embodiments, the protein-coding sequence comprises or consists of the nucleotide sequence of SEQ ID NO: 49. atgcggctgctggccaaaatcatctgtctgatgctgtgggccatctgtgtggccgaggattg caacgagctgccccctagacgcaatacagagatcctgacaggcagctggtccgaccagacat accctgagggaacccaggccatctacaagtgcagaccaggatatcggtccctgggaaatgtg ataatggtgtgtagaaagggagagtgggtggctctgaaccctctgaggaaatgccagaagcg cccatgcggccaccccggcgatacccccttcggcaccttcacactgaccggcggcaatgtgt ttgagtatggcgtgaaggccgtgtacacctgcaacgagggctaccagctgctgggtgagatt aactaccgcgagtgtgataccgacggctggaccaacgacatccccatctgtgaagtggtgaa gtgtctgcccgtgaccgcaccagagaatggcaaaatcgtgagttctgccatggagcctgata gggagtaccactttggccaggccgtgcgctttgtgtgtaattctggctacaagatcgagggc gacgaggagatgcattgctctgacgatggcttctggtcaaaggaaaagcccaaatgcgtgga gattagctgtaagtccccagacgtcatcaacggctcccctatctctcagaagatcatttaca aggagaatgaacggtttcagtataaatgcaacatgggctacgagtactccgagcggggcgat gccgtgtgtaccgagtcagggtggcgaccactccctagttgtgaagagaagagctgcgacaa tccctacatccccaacggcgactactctccactgaggatcaagcacaggacaggcgacgaga tcacctaccagtgccgcaacgggttttaccctgccacaaggggcaatactgccaagtgcacc agcacagggtggattcctgccccccggtgtacactgaagccatgcgattacccagatatcaa acatgggggcctgtaccatgagaatatgaggcggccatactttcccgtggccgtgggcaagt actactcctactattgcgacgagcactttgagacaccctccggctcctactgggaccatatc cactgtacccaggatggctggtcccctgccgtgccatgtctgagaaaatgctacttccccta tctggagaacgggtacaaccagaaccacgggaggaagttcgttcaggggaagtccattgacg tggcctgccatcccggctacgccctgcccaaggcccagactactgtgacctgcatggagaat ggttggagccccaccccccggtgtatccgggtgagctttaccctgggaagcggagctactaa cttcagcctgctgaagcaggctggcgacgtggaggagaaccctggacctatgaagctgctgc atgtgttcctgttgttcctgtgttttcacctgagattttgtaaggtgacttataccagccag gaagacctggtagagaagaagtgcctggccaagaagtatactcacctgtcttgcgataaggt gttctgccagccttggcagcggtgcatcgagggcacctgtgtgtgcaagctgccctatcagt gtcccaagaatgggaccgccgtgtgtgccaccaacagaaggagcttccccacctattgccag cagaagagcctggagtgtctgcaccccggcaccaagttcctgaataatggcacatgtaccgc cgagggcaagttctcagtctccctgaagcatggcaacactgacagtgagggcatcgtggagg tgaaactggtggaccaggacaagacaatgttcatctgtaagtcatcttggtctatgcgggag gccaacgtggcctgcctggatctgggcttccagcagggggccgatacccagaggcgattcaa gctgagcgatctgtctataaacagcaccgagtgcctgcacgtgcactgcaggggcctggaaa cctctctggccgaatgcaccttcaccaagagacggactatgggctaccaggattttgccgat gtggtgtgctatacccagaaagccgactcccccatggacgacttcttccaatgtgtcaatgg aaagtacatcagtcagatgaaggcatgtgacggcattaacgattgtggcgatcagagcgatg agctgtgctgtaaggcctgccagggaaagggcttccactgcaaatccggcgtgtgcatccct agccagtaccagtgtaatggcgaggtggactgtatcacaggagaggacgaagtgggatgcgc tggattcgctagtgtgacccaggaggagaccgagatcctgaccgccgacatggatgccgaga ggagacgtatcaagtccctgctgcctaagctgtcttgtggagtgaagaataggatgcacatc agacgcaagagaatcgtcggcggcaagcgcgcccagctgggcgatctgccctggcaagtggc cattaaggacgcctccggcatcacatgtggaggaatatacataggcgggtgctggatcctga ccgccgcccactgcctgcgggcctctaaaactcataggtaccagatctggacaaccgtggtg gattggatccatcctgatctgaagagaatcgtgatcgagtacgtcgataggattatctttca cgagaactataatgccgggacctaccagaatgacatcgctctcattgagatgaagaaggatg gcaacaagaaggactgcgagctgcccaggagcattcccgcttgcgtgccatggtccccatac ctgttccagccaaacgacacctgcatcgtgagcggctggggcagagaaaaggacaacgagag agtgttctccctgcagtggggcgaagtgaagctgatttccaactgcagtaagttctacggca accgcttctatgagaaggagatggagtgtgccggcacatacgacggcagcatcgacgcctgc aagggcgacagcggcggccccctggtgtgcatggacgccaacaacgtgacctatgtgtgggg ggtggtgtcctggggcgagaactgtggaaagccagagttccctggagtgtataccaaggtgg ccaactacttcgattggatcagctaccacgtcggcaggcccttcatcagccagtacaacgtt Example FHL1-P2A-CFI nucleotide sequence (SEQ ID NO: 49) 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, wherein the regulatory element comprises a super core promoter, and / or 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 a complement inhibitor; 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: 50, or a variant which is at least 70% identical to SEQ ID NO: 50. 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: 50. In preferred embodiments, the WPRE consists of the nucleotide sequence shown as SEQ ID NO: 50. aatcaacctctggattacaaaatttgtgaaagattgactggtattcttaactatgttgctcc ttttacgctatgtggatacgctgctttaatgcctttgtatcatgctattgcttcccgtatgg ctttcattttctcctccttgtataaatcctggttgctgtctctttatgaggagttgtggccc gttgtcaggcaacgtggcgtggtgtgcactgtgtttgctgacgcaacccccactggttgggg cattgccaccacctgtcagctcctttccgggactttcgctttccccctccctattgccacgg cggaactcatcgccgcctgccttgcccgctgctggacaggggctcggctgttgggcactgac aattccgtggtgttgtcggggaaatcatcgtcctttccttggctgctcgcctgtgttgccac ctggattctgcgcgggacgtccttctgctacgtcccttcggccctcaatccagcggaccttc cttcccgcggcctgctgccggctctgcggcctcttccgcgtcttcgccttcgccctcagacg agtcggatctccctttgggccgcctccccgc Example WPRE (SEQ ID NO: 50) 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, wherein the regulatory element comprises a super core promoter, and / or 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 a complement inhibitor; 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, wherein the regulatory element comprises a super core promoter, and / or 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 a complement inhibitor; a WPRE; a polyadenylation sequence; and a 3’ ITR. Suitable polyadenylation sequence 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: 51, or a variant which is at least 70% identical to SEQ ID NO: 51. 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: 51. In preferred embodiments, the polyadenylation sequence consists of the nucleotide sequence shown as SEQ ID NO: 51. ctgtgccttctagttgccagccatctgttgtttgcccctcccccgtgccttccttgaccctg gaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgag taggtgtcattctattctggggggtggggtggggcaggacagcaagggggaggattgggaag acaatagcaggcatgctggggatgcggtgggctctatgg Example bGH poly(A) sequence (SEQ ID NO: 51) 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, wherein the regulatory element comprises a super core promoter, and / or 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 a complement inhibitor; 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: 77 or SEQ ID NO: 78. Suitably, the Kozak sequence may comprise or consist of the nucleotide sequence of SEQ ID NO: 77 or 78, 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: 77) gccgccrccatgg Example consensus Kozak sequence 2 (SEQ ID NO: 78) Suitably, the Kozak sequence may comprise or consist of the nucleotide sequence shown as SEQ ID NO: 79, or a variant which is at least 65% identical to SEQ ID NO: 79. Suitably, the variant may be at least 75%, or at least 85% identical to SEQ ID NO: 79. In some embodiments, the Kozak sequence comprises or consists of the nucleotide sequence shown as SEQ ID NO: 79. In some embodiments, the Kozak sequence consists of the nucleotide sequence shown as SEQ ID NO: 79. tccaccatg Example Kozak sequence (SEQ ID NO: 79) 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: 82. 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: 82. In some embodiments, the 5’ ITR comprises or consists of the nucleotide sequence of SEQ ID NO: 82. cctgcaggcagctgcgcgctcgctcgctcactgaggccgcccgggcaaagcccgggcgtcgg gcgacctttggtcgcccggcctcagtgagcgagcgagcgcgcagagagggagtggccaactc catcactaggggttcct Example 5’ ITR (SEQ ID NO: 82) 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: 83. 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: 83. In some embodiments, the 3’ ITR comprises or consists of the nucleotide sequence of SEQ ID NO: 83. aggaacccctagtgatggagttggccactccctctctgcgcgctcgctcgctcactgaggcc gggcgaccaaaggtcgcccgacgcccgggctttgcccgggcggcctcagtgagcgagcgagc gcgcagctgcctgcagg Example 3’ ITR (SEQ ID NO: 83) 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: 82 and a 3’ ITR comprising or consisting of a nucleotide sequence which is at least 70% identical to SEQ ID NO: 83. In some embodiments, the polynucleotide of the invention comprises a 5’ ITR comprising or consisting of the nucleotide sequence of SEQ ID NO: 82 and a 3’ ITR comprising or consisting of the nucleotide sequence of SEQ ID NO: 83. 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: 16)10bptcgaactggacatga (SEQ ID NO: 17)15bptgtcagaaaagcggtcat (SEQ ID NO: 18)18bptggcgtatatgccggcaaca (SEQ ID NO: 19)20bpccggatcggtaagagaaagctcatt (SEQ ID NO: 20)25bpacatacggtaccgggtcgaatggaatgcct (SEQ ID NO: 21)30bpgcttgtagatggccaattgagctcccaggcatgacttaat (SEQ ID NO: 22)40bpcataccccgtcttctggccaagtggcaagtctatgagcggtgtatgaacaaatcggtc 60bp at (SEQ ID NO: 23) gaactgaccgaattaccagccctctagaaaaccaagtagcaaagccaggtttcgccca 80bp tggctcatcgtcagctgaccgg (SEQ ID NO: 24) aaagacaaggagggggtgatgtcggcaggttaccacaccggcggaacatgatatttag 100bp aatgtacgccgcggttatccccccgttttaacctaacttcgt (SEQ ID NO: 25) In some embodiments, the polynucleotide comprises from 5’ to 3’: a 5’ ITR; a kidney-specific promoter; a first spacer sequence; a regulatory element, wherein the regulatory element comprises a super core promoter, or 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 a complement inhibitor; 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, wherein the regulatory element comprises a super core promoter, or 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 a complement inhibitor; 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, wherein the regulatory element comprises a super core promoter, or 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 a complement inhibitor; 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, wherein the regulatory element comprises a super core promoter, or 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 a complement inhibitor; 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, wherein the regulatory element comprises a super core promoter, or 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 a complement inhibitor; 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 polynucleotides In preferred embodiments, the polynucleotide does not comprise any further nucleotide sequences, except for spacer sequences. Suitably, the example polynucleotides described below may comprise the recited elements from 5’ to 3’. SCP1-CFI polynucleotide In some embodiments, the polynucleotide comprises: a 5’ ITR; a kidney-specific promoter; a super core promoter; a protein coding sequence encoding CFI; 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: 2; a super core promoter consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 5; a CFI coding sequence consisting of a nucleotide sequence having at least 80% sequence identity to any of SEQ ID NOs: 33 to 35; optionally, a WPRE consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 51; 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: 2; a super core promoter consisting of a nucleotide sequence having at least 85% sequence identity to SEQ ID NO: 5; a CFI coding sequence consisting of a nucleotide sequence having at least 85% sequence identity to any of SEQ ID NOs: 33 to 35; optionally, a WPRE consisting of a nucleotide sequence having at least 85% sequence identity to SEQ ID NO: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 85% sequence identity to SEQ ID NO: 51; 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: 2; a super core promoter consisting of a nucleotide sequence having at least 90% sequence identity to SEQ ID NO: 5; a CFI coding sequence consisting of a nucleotide sequence having at least 90% sequence identity to any of SEQ ID NOs: 33 to 35; optionally, a WPRE consisting of a nucleotide sequence having at least 90% sequence identity to SEQ ID NO: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 90% sequence identity to SEQ ID NO: 51; 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: 2; a super core promoter consisting of a nucleotide sequence having at least 95% sequence identity to SEQ ID NO: 5; a CFI coding sequence consisting of a nucleotide sequence having at least 95% sequence identity to any of SEQ ID NOs: 33 to 35; optionally, a WPRE consisting of a nucleotide sequence having at least 95% sequence identity to SEQ ID NO: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 95% sequence identity to SEQ ID NO: 51; 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: 2; a super core promoter consisting of a nucleotide sequence having at least 96% sequence identity to SEQ ID NO: 5; a CFI coding sequence consisting of a nucleotide sequence having at least 96% sequence identity to any of SEQ ID NOs: 33 to 35; optionally, a WPRE consisting of a nucleotide sequence having at least 96% sequence identity to SEQ ID NO: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 96% sequence identity to SEQ ID NO: 51; 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: 2; a super core promoter consisting of a nucleotide sequence having at least 97% sequence identity to SEQ ID NO: 5; a CFI coding sequence consisting of a nucleotide sequence having at least 97% sequence identity to any of SEQ ID NOs: 33 to 35; optionally, a WPRE consisting of a nucleotide sequence having at least 97% sequence identity to SEQ ID NO: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 97% sequence identity to SEQ ID NO: 51; 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: 2; a super core promoter consisting of a nucleotide sequence having at least 98% sequence identity to SEQ ID NO: 5; a CFI coding sequence consisting of a nucleotide sequence having at least 98% sequence identity to any of SEQ ID NOs: 33 to 35; optionally, a WPRE consisting of a nucleotide sequence having at least 98% sequence identity to SEQ ID NO: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 98% sequence identity to SEQ ID NO: 51; 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: 2; a super core promoter consisting of a nucleotide sequence having at least 99% sequence identity to SEQ ID NO: 5; a CFI coding sequence consisting of a nucleotide sequence having at least 99% sequence identity to any of SEQ ID NOs: 33 to 35; optionally, a WPRE consisting of a nucleotide sequence having at least 99% sequence identity to SEQ ID NO: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 99% sequence identity to SEQ ID NO: 51; 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: 2; a super core promoter consisting of the nucleotide sequence of SEQ ID NO: 5; a CFI coding sequence consisting of the nucleotide sequence of any of SEQ ID NOs: 33 to 35; optionally, a WPRE consisting of the nucleotide sequence of SEQ ID NO: 50; optionally, a polyadenylation sequence consisting of the nucleotide sequence of SEQ ID NO: 51; and a 3’ ITR. SCP1-CFI (codon-optimised) polynucleotide In some embodiments, the polynucleotide comprises: a 5’ ITR; a kidney-specific promoter; a super core promoter; a codon-optimised protein coding sequence encoding CFI; 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: 2; a super core promoter consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 5; a CFI coding sequence consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 33; optionally, a WPRE consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 51; 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: 2; a super core promoter consisting of a nucleotide sequence having at least 85% sequence identity to SEQ ID NO: 5; a CFI coding sequence consisting of a nucleotide sequence having at least 85% sequence identity to SEQ ID NO: 33; optionally, a WPRE consisting of a nucleotide sequence having at least 85% sequence identity to SEQ ID NO: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 85% sequence identity to SEQ ID NO: 51; 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: 2; a super core promoter consisting of a nucleotide sequence having at least 90% sequence identity to SEQ ID NO: 5; a CFI coding sequence consisting of a nucleotide sequence having at least 90% sequence identity to SEQ ID NO: 33; optionally, a WPRE consisting of a nucleotide sequence having at least 90% sequence identity to SEQ ID NO: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 90% sequence identity to SEQ ID NO: 51; 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: 2; a super core promoter consisting of a nucleotide sequence having at least 95% sequence identity to SEQ ID NO: 5; a CFI coding sequence consisting of a nucleotide sequence having at least 95% sequence identity to SEQ ID NO: 33; optionally, a WPRE consisting of a nucleotide sequence having at least 95% sequence identity to SEQ ID NO: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 95% sequence identity to SEQ ID NO: 51; 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: 2; a super core promoter consisting of a nucleotide sequence having at least 96% sequence identity to SEQ ID NO: 5; a CFI coding sequence consisting of a nucleotide sequence having at least 96% sequence identity to SEQ ID NO: 33; optionally, a WPRE consisting of a nucleotide sequence having at least 96% sequence identity to SEQ ID NO: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 96% sequence identity to SEQ ID NO: 51; 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: 2; a super core promoter consisting of a nucleotide sequence having at least 97% sequence identity to SEQ ID NO: 5; a CFI coding sequence consisting of a nucleotide sequence having at least 97% sequence identity to SEQ ID NO: 33; optionally, a WPRE consisting of a nucleotide sequence having at least 97% sequence identity to SEQ ID NO: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 97% sequence identity to SEQ ID NO: 51; 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: 2; a super core promoter consisting of a nucleotide sequence having at least 98% sequence identity to SEQ ID NO: 5; a CFI coding sequence consisting of a nucleotide sequence having at least 98% sequence identity to SEQ ID NO: 33; optionally, a WPRE consisting of a nucleotide sequence having at least 98% sequence identity to SEQ ID NO: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 98% sequence identity to SEQ ID NO: 51; 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: 2; a super core promoter consisting of a nucleotide sequence having at least 99% sequence identity to SEQ ID NO: 5; a CFI coding sequence consisting of a nucleotide sequence having at least 99% sequence identity to SEQ ID NO: 33; optionally, a WPRE consisting of a nucleotide sequence having at least 99% sequence identity to SEQ ID NO: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 99% sequence identity to SEQ ID NO: 51; 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: 2; a super core promoter consisting of the nucleotide sequence of SEQ ID NO: 5; a CFI coding sequence consisting of the nucleotide sequence of SEQ ID NO: 33; optionally, a WPRE consisting of the nucleotide sequence of SEQ ID NO: 50; optionally, a polyadenylation sequence consisting of the nucleotide sequence of SEQ ID NO: 51; and a 3’ ITR. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 70% identical to SEQ ID NO: 52. 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: 52. In some embodiments, the polynucleotide comprises the nucleotide sequence SEQ ID NO: 52. ggccctggggtcacggaggctggggaggcaccgaggaacgcgcctggcatgtgctgacaggg gattttatgctccaggagcaagacagagagagatactcacagggaagaggggaagaggaaaa cgagaaagggaggagagtaacggaaagagataaaaaagaaaagcaggtggcagagacacaca gagagggacccagagaaagccagacagacgcaggtggctggcagcgggcgctgtgggggtca cagtagggggacctgtg(n) gtacttatataagggggtgggggcgcgttcgtcctcagtcg cgatcgaacactcgagccgagcagacgtgcctacggaccg(n) atgaagctgctgcatgtg ttcctgttgttcctgtgttttcacctgagattttgtaaggtgacttataccagccaggaaga cctggtagagaagaagtgcctggccaagaagtatactcacctgtcttgcgataaggtgttct gccagccttggcagcggtgcatcgagggcacctgtgtgtgcaagctgccctatcagtgtccc aagaatgggaccgccgtgtgtgccaccaacagaaggagcttccccacctattgccagcagaa gagcctggagtgtctgcaccccggcaccaagttcctgaataatggcacatgtaccgccgagg gcaagttctcagtctccctgaagcatggcaacactgacagtgagggcatcgtggaggtgaaa ctggtggaccaggacaagacaatgttcatctgtaagtcatcttggtctatgcgggaggccaa cgtggcctgcctggatctgggcttccagcagggggccgatacccagaggcgattcaagctga gcgatctgtctataaacagcaccgagtgcctgcacgtgcactgcaggggcctggaaacctct ctggccgaatgcaccttcaccaagagacggactatgggctaccaggattttgccgatgtggt gtgctatacccagaaagccgactcccccatggacgacttcttccaatgtgtcaatggaaagt acatcagtcagatgaaggcatgtgacggcattaacgattgtggcgatcagagcgatgagctg tgctgtaaggcctgccagggaaagggcttccactgcaaatccggcgtgtgcatccctagcca gtaccagtgtaatggcgaggtggactgtatcacaggagaggacgaagtgggatgcgctggat tcgctagtgtgacccaggaggagaccgagatcctgaccgccgacatggatgccgagaggaga cgtatcaagtccctgctgcctaagctgtcttgtggagtgaagaataggatgcacatcagacg caagagaatcgtcggcggcaagcgcgcccagctgggcgatctgccctggcaagtggccatta aggacgcctccggcatcacatgtggaggaatatacataggcgggtgctggatcctgaccgcc gcccactgcctgcgggcctctaaaactcataggtaccagatctggacaaccgtggtggattg gatccatcctgatctgaagagaatcgtgatcgagtacgtcgataggattatctttcacgaga actataatgccgggacctaccagaatgacatcgctctcattgagatgaagaaggatggcaac aagaaggactgcgagctgcccaggagcattcccgcttgcgtgccatggtccccatacctgtt ccagccaaacgacacctgcatcgtgagcggctggggcagagaaaaggacaacgagagagtgt tctccctgcagtggggcgaagtgaagctgatttccaactgcagtaagttctacggcaaccgc ttctatgagaaggagatggagtgtgccggcacatacgacggcagcatcgacgcctgcaaggg cgacagcggcggccccctggtgtgcatggacgccaacaacgtgacctatgtgtggggggtgg tgtcctggggcgagaactgtggaaagccagagttccctggagtgtataccaaggtggccaac tacttcgattggatcagctaccacgtcggcaggcccttcatcagccagtacaacgtttaa(n ) aatcaacctctggattacaaaatttgtgaaagattgactggtattcttaactatgttgct ccttttacgctatgtggatacgctgctttaatgcctttgtatcatgctattgcttcccgtat ggctttcattttctcctccttgtataaatcctggttgctgtctctttatgaggagttgtggc ccgttgtcaggcaacgtggcgtggtgtgcactgtgtttgctgacgcaacccccactggttgg ggcattgccaccacctgtcagctcctttccgggactttcgctttccccctccctattgccac ggcggaactcatcgccgcctgccttgcccgctgctggacaggggctcggctgttgggcactg acaattccgtggtgttgtcggggaaatcatcgtcctttccttggctgctcgcctgtgttgcc acctggattctgcgcgggacgtccttctgctacgtcccttcggccctcaatccagcggacct tccttcccgcggcctgctgccggctctgcggcctcttccgcgtcttcgccttcgccctcaga cgagtcggatctccctttgggccgcctccccgc(n) ctgtgccttctagttgccagccatc tgttgtttgcccctcccccgtgccttccttgaccctggaaggtgccactcccactgtccttt cctaataaaatgaggaaattgcatcgcattgtctgagtaggtgtcattctattctggggggt ggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctggggatgc ggtgggctctatgg 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 SCP1-CFI (codon-optimised) polynucleotide (SEQ ID NO: 52) 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)x4is independently selected from any of SEQ ID NOs: 16-28. In some embodiments, (n)x1is selected from any of SEQ ID NOs: 16- 28. In some embodiments, (n)x2 is selected from any of SEQ ID NOs: 16-28. In some embodiments, (n)x3 is selected from any of SEQ ID NOs: 16-28. In some embodiments, (n)x4 is selected from any of SEQ ID NOs: 16-28. SCP1-CFI (wild-type) polynucleotide In some embodiments, the polynucleotide comprises: a 5’ ITR; a kidney-specific promoter; a super core promoter; a wild-type protein coding sequence encoding CFI; 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: 2; a super core promoter consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 5; a CFI coding sequence consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 34; optionally, a WPRE consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 51; 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: 2; a super core promoter consisting of a nucleotide sequence having at least 85% sequence identity to SEQ ID NO: 5; a CFI coding sequence consisting of a nucleotide sequence having at least 85% sequence identity to SEQ ID NO: 34; optionally, a WPRE consisting of a nucleotide sequence having at least 85% sequence identity to SEQ ID NO: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 85% sequence identity to SEQ ID NO: 51; 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: 2; a super core promoter consisting of a nucleotide sequence having at least 90% sequence identity to SEQ ID NO: 5; a CFI coding sequence consisting of a nucleotide sequence having at least 90% sequence identity to SEQ ID NO: 34; optionally, a WPRE consisting of a nucleotide sequence having at least 90% sequence identity to SEQ ID NO: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 90% sequence identity to SEQ ID NO: 51; 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: 2; a super core promoter consisting of a nucleotide sequence having at least 95% sequence identity to SEQ ID NO: 5; a CFI coding sequence consisting of a nucleotide sequence having at least 95% sequence identity to SEQ ID NO: 34; optionally, a WPRE consisting of a nucleotide sequence having at least 95% sequence identity to SEQ ID NO: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 95% sequence identity to SEQ ID NO: 51; 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: 2; a super core promoter consisting of a nucleotide sequence having at least 96% sequence identity to SEQ ID NO: 5; a CFI coding sequence consisting of a nucleotide sequence having at least 96% sequence identity to SEQ ID NO: 34; optionally, a WPRE consisting of a nucleotide sequence having at least 96% sequence identity to SEQ ID NO: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 96% sequence identity to SEQ ID NO: 51; 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: 2; a super core promoter consisting of a nucleotide sequence having at least 97% sequence identity to SEQ ID NO: 5; a CFI coding sequence consisting of a nucleotide sequence having at least 97% sequence identity to SEQ ID NO: 34; optionally, a WPRE consisting of a nucleotide sequence having at least 97% sequence identity to SEQ ID NO: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 97% sequence identity to SEQ ID NO: 51; 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: 2; a super core promoter consisting of a nucleotide sequence having at least 98% sequence identity to SEQ ID NO: 5; a CFI coding sequence consisting of a nucleotide sequence having at least 98% sequence identity to SEQ ID NO: 34; optionally, a WPRE consisting of a nucleotide sequence having at least 98% sequence identity to SEQ ID NO: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 98% sequence identity to SEQ ID NO: 51; 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: 2; a super core promoter consisting of a nucleotide sequence having at least 99% sequence identity to SEQ ID NO: 5; a CFI coding sequence consisting of a nucleotide sequence having at least 99% sequence identity to SEQ ID NO: 34; optionally, a WPRE consisting of a nucleotide sequence having at least 99% sequence identity to SEQ ID NO: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 99% sequence identity to SEQ ID NO: 51; 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: 2; a super core promoter consisting of the nucleotide sequence of SEQ ID NO: 5; a CFI coding sequence consisting of the nucleotide sequence of SEQ ID NO: 34; optionally, a WPRE consisting of the nucleotide sequence of SEQ ID NO: 50; optionally, a polyadenylation sequence consisting of the nucleotide sequence of SEQ ID NO: 51; and a 3’ ITR. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 70% identical to SEQ ID NO: 53. 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: 53. In some embodiments, the polynucleotide comprises the nucleotide sequence SEQ ID NO: 53. ggccctggggtcacggaggctggggaggcaccgaggaacgcgcctggcatgtgctgacaggg gattttatgctccaggagcaagacagagagagatactcacagggaagaggggaagaggaaaa cgagaaagggaggagagtaacggaaagagataaaaaagaaaagcaggtggcagagacacaca gagagggacccagagaaagccagacagacgcaggtggctggcagcgggcgctgtgggggtca cagtagggggacctgtg(n) gtacttatataagggggtgggggcgcgttcgtcctcagtcg cgatcgaacactcgagccgagcagacgtgcctacggaccg(n) atgaagcttcttcatgtt ttcctgttatttctgtgcttccacttaaggttttgcaaggtcacttatacatctcaagagga tctggtggagaaaaagtgcttagcaaaaaaatatactcacctctcctgcgataaagtcttct gccagccatggcagagatgcattgagggcacctgtgtttgtaaactaccgtatcagtgccca aagaatggcactgcagtgtgtgcaactaacaggagaagcttcccaacatactgtcaacaaaa gagtttggaatgtcttcatccagggacaaagtttttaaataacggaacatgcacagccgaag gaaagtttagtgtttccttgaagcatggaaatacagattcagagggaatagttgaagtaaaa cttgtggaccaagataagacaatgttcatatgcaaaagcagctggagcatgagggaagccaa cgtggcctgccttgaccttgggtttcaacaaggtgctgatactcaaagaaggtttaagttgt ctgatctctctataaattccactgaatgtctacatgtgcattgccgaggattagagaccagt ttggctgaatgtacttttactaagagaagaactatgggttaccaggatttcgctgatgtggt ttgttatacacagaaagcagattctccaatggatgacttctttcagtgtgtgaatgggaaat acatttctcagatgaaagcctgtgatggtatcaatgattgtggagaccaaagtgatgaactg tgttgtaaagcatgccaaggcaaaggcttccattgcaaatcgggtgtttgcattccaagcca gtatcaatgcaatggtgaggtggactgcattacaggggaagatgaagttggctgtgcaggct ttgcatctgtgactcaagaagaaacagaaattttgactgctgacatggatgcagaaagaaga cggataaaatcattattacctaaactatcttgtggagttaaaaacagaatgcacattcgaag gaaacgaattgtgggaggaaagcgagcacaactgggagacctcccatggcaggtggcaatta aggatgccagtggaatcacctgtgggggaatttatattggtggctgttggattctgactgct gcacattgtctcagagccagtaaaactcatcgttaccaaatatggacaacagtagtagactg gatacaccccgaccttaaacgtatagtaattgaatacgtggatagaattattttccatgaaa actacaatgcaggcacttaccaaaatgacatcgctttgattgaaatgaaaaaagacggaaac aaaaaagattgtgagctgcctcgttccatccctgcctgtgtcccctggtctccttacctatt ccaacctaatgatacatgcatcgtttctggctggggacgagaaaaagataacgaaagagtct tttcacttcagtggggtgaagttaaactaataagcaactgctctaagttttacggaaatcgt ttctatgaaaaagaaatggaatgtgcaggtacatatgatggttccatcgatgcctgtaaagg ggactctggaggccccttagtctgtatggatgccaacaatgtgacttatgtctggggtgttg tgagttggggggaaaactgtggaaaaccagagttcccaggtgtttacaccaaagtggccaat tattttgactggattagctaccatgtaggaaggccttttatttctcagtacaatgtataa(n ) aatcaacctctggattacaaaatttgtgaaagattgactggtattcttaactatgttgct ccttttacgctatgtggatacgctgctttaatgcctttgtatcatgctattgcttcccgtat ggctttcattttctcctccttgtataaatcctggttgctgtctctttatgaggagttgtggc ccgttgtcaggcaacgtggcgtggtgtgcactgtgtttgctgacgcaacccccactggttgg ggcattgccaccacctgtcagctcctttccgggactttcgctttccccctccctattgccac ggcggaactcatcgccgcctgccttgcccgctgctggacaggggctcggctgttgggcactg acaattccgtggtgttgtcggggaaatcatcgtcctttccttggctgctcgcctgtgttgcc acctggattctgcgcgggacgtccttctgctacgtcccttcggccctcaatccagcggacct tccttcccgcggcctgctgccggctctgcggcctcttccgcgtcttcgccttcgccctcaga cgagtcggatctccctttgggccgcctccccgc(n) ctgtgccttctagttgccagccatc tgttgtttgcccctcccccgtgccttccttgaccctggaaggtgccactcccactgtccttt cctaataaaatgaggaaattgcatcgcattgtctgagtaggtgtcattctattctggggggt ggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctggggatgc ggtgggctctatgg 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 SCP1-CFI (wild-type) polynucleotide (SEQ ID NO: 53) 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)x4is independently selected from any of SEQ ID NOs: 16-28. In some embodiments, (n)x1is selected from any of SEQ ID NOs: 16- 28. In some embodiments, (n)x2is selected from any of SEQ ID NOs: 16-28. In some embodiments, (n)x3is selected from any of SEQ ID NOs: 16-28. In some embodiments, (n)x4is selected from any of SEQ ID NOs: 16-28. SCP1-CFI (mutant) polynucleotide In some embodiments, the polynucleotide comprises: a 5’ ITR; a kidney-specific promoter; a super core promoter; a mutant protein coding sequence encoding CFI; 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: 2; a super core promoter consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 5; a CFI coding sequence consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 35; optionally, a WPRE consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 51; 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: 2; a super core promoter consisting of a nucleotide sequence having at least 85% sequence identity to SEQ ID NO: 5; a CFI coding sequence consisting of a nucleotide sequence having at least 85% sequence identity to SEQ ID NO: 35; optionally, a WPRE consisting of a nucleotide sequence having at least 85% sequence identity to SEQ ID NO: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 85% sequence identity to SEQ ID NO: 51; 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: 2; a super core promoter consisting of a nucleotide sequence having at least 90% sequence identity to SEQ ID NO: 5; a CFI coding sequence consisting of a nucleotide sequence having at least 90% sequence identity to SEQ ID NO: 35; optionally, a WPRE consisting of a nucleotide sequence having at least 90% sequence identity to SEQ ID NO: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 90% sequence identity to SEQ ID NO: 51; 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: 2; a super core promoter consisting of a nucleotide sequence having at least 95% sequence identity to SEQ ID NO: 5; a CFI coding sequence consisting of a nucleotide sequence having at least 95% sequence identity to SEQ ID NO: 35; optionally, a WPRE consisting of a nucleotide sequence having at least 95% sequence identity to SEQ ID NO: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 95% sequence identity to SEQ ID NO: 51; 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: 2; a super core promoter consisting of a nucleotide sequence having at least 96% sequence identity to SEQ ID NO: 5; a CFI coding sequence consisting of a nucleotide sequence having at least 96% sequence identity to SEQ ID NO: 35; optionally, a WPRE consisting of a nucleotide sequence having at least 96% sequence identity to SEQ ID NO: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 96% sequence identity to SEQ ID NO: 51; 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: 2; a super core promoter consisting of a nucleotide sequence having at least 97% sequence identity to SEQ ID NO: 5; a CFI coding sequence consisting of a nucleotide sequence having at least 97% sequence identity to SEQ ID NO: 35; optionally, a WPRE consisting of a nucleotide sequence having at least 97% sequence identity to SEQ ID NO: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 97% sequence identity to SEQ ID NO: 51; 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: 2; a super core promoter consisting of a nucleotide sequence having at least 98% sequence identity to SEQ ID NO: 5; a CFI coding sequence consisting of a nucleotide sequence having at least 98% sequence identity to SEQ ID NO: 35; optionally, a WPRE consisting of a nucleotide sequence having at least 98% sequence identity to SEQ ID NO: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 98% sequence identity to SEQ ID NO: 51; 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: 2; a super core promoter consisting of a nucleotide sequence having at least 99% sequence identity to SEQ ID NO: 5; a CFI coding sequence consisting of a nucleotide sequence having at least 99% sequence identity to SEQ ID NO: 35; optionally, a WPRE consisting of a nucleotide sequence having at least 99% sequence identity to SEQ ID NO: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 99% sequence identity to SEQ ID NO: 51; 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: 2; a super core promoter consisting of the nucleotide sequence of SEQ ID NO: 5; a CFI coding sequence consisting of the nucleotide sequence of SEQ ID NO: 35; optionally, a WPRE consisting of the nucleotide sequence of SEQ ID NO: 50; optionally, a polyadenylation sequence consisting of the nucleotide sequence of SEQ ID NO: 51; and a 3’ ITR. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 70% identical to SEQ ID NO: 54. 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: 54. In some embodiments, the polynucleotide comprises the nucleotide sequence SEQ ID NO: 54. ggccctggggtcacggaggctggggaggcaccgaggaacgcgcctggcatgtgctgacaggg gattttatgctccaggagcaagacagagagagatactcacagggaagaggggaagaggaaaa cgagaaagggaggagagtaacggaaagagataaaaaagaaaagcaggtggcagagacacaca gagagggacccagagaaagccagacagacgcaggtggctggcagcgggcgctgtgggggtca cagtagggggacctgtg(n) gtacttatataagggggtgggggcgcgttcgtcctcagtcg cgatcgaacactcgagccgagcagacgtgcctacggaccg(n) atgaagctgctgcatgtg ttcctgctgttcctgtgcttccacctgagattctgcaaggtgacctacaccagccaggagga cctggtggagaagaagtgcctggccaagaagtacacccacctgagctgtgacaaggtgttct gccagccctggcagctgtgcattgagggcacctgtgtgtgcaagctgccctaccagtgcccc aagaatggcacagctgtgtgtgccaccaacagaaggagcttccccacctactgccagcagaa gagcctggagtgcctgcaccctggcaccaagttcctgaacaatggcacctgcacagctgagg gcaagttcagtgtgagcctgaagcatggcaacacagacagtgagggcattgtggaggtgaag ctggtggaccaggacaagaccatgttcatctgcaagagcagttggagcatgagagaggccaa tgtggcctgcctggacctgggcttccagcaaggagctgacacccagagaaggttcaagctga gtgacctgagcatcaacagcacagagtgcctgcatgtgcactgcagaggcctggagaccagc ctggctgagtgcaccttcaccaagagaaggaccatgggctaccaggactttgctgatgtggt ttgctacacccagaaggctgacagccccatggatgacttcttccagtgtgtgaatggcaagt acatcagccagatgaaggcctgtgatggcatcaatgactgtggagaccagagtgatgagctg tgctgcaaggcctgccagggcaagggcttccactgcaagagtggagtgtgcatccccagcca gtaccagtgcaatggagaggtggactgcatcacaggagaggatgaggtgggctgtgctggct ttgccagtgtgacccaggaggagacagagatcctgacagctgacatggatgctgagagaagg agaatcaagagcctgctgcccaagctgagctgtggagtgaagaacagaatgcacatcagaag gaagagaattgtgggaggcaagagagcccagctgggagacctgccctggcaggtggccatca aggatgccagtggcatcacctgtggaggaatctacattggaggctgctggattctgacagct gcccactgcctgtatgccagcaagacccacagataccagatctggaccacagtggttgactg gattcaccctgacctgaagagaattgtgattgagtatgtggacagaatcattttccatgaga actacaatgctggcacctaccagaatgacattgccctgattgagatgaagaaggatggcaac aagaaagactgtgagctgcccagaagcatccctgcctgtgtgccctggagcccctacctgtt ccagcccaatgacacctgtattgtcagtggatggggcagagagaaggacaatgagagagtgt tcagcctgcagtggggagaggtgaagctgatcagcaactgcagcaagttctatggcaacaga ttctatgagaaggagatggagtgtgctggcacctatgatggcagcattgatgcctgcaaggg agacagtggaggccccctggtgtgcatggatgccaacaatgtgacctatgtgtggggagtgg ttagctggggagagaactgtggcaagcctgagttccctggagtgtacaccaaggtggccaac tactttgactggatcagctaccatgtgggcagacccttcatcagccagtacaatgtgtaa(n ) aatcaacctctggattacaaaatttgtgaaagattgactggtattcttaactatgttgct ccttttacgctatgtggatacgctgctttaatgcctttgtatcatgctattgcttcccgtat ggctttcattttctcctccttgtataaatcctggttgctgtctctttatgaggagttgtggc ccgttgtcaggcaacgtggcgtggtgtgcactgtgtttgctgacgcaacccccactggttgg ggcattgccaccacctgtcagctcctttccgggactttcgctttccccctccctattgccac ggcggaactcatcgccgcctgccttgcccgctgctggacaggggctcggctgttgggcactg acaattccgtggtgttgtcggggaaatcatcgtcctttccttggctgctcgcctgtgttgcc acctggattctgcgcgggacgtccttctgctacgtcccttcggccctcaatccagcggacct tccttcccgcggcctgctgccggctctgcggcctcttccgcgtcttcgccttcgccctcaga cgagtcggatctccctttgggccgcctccccgc(n) ctgtgccttctagttgccagccatc tgttgtttgcccctcccccgtgccttccttgaccctggaaggtgccactcccactgtccttt cctaataaaatgaggaaattgcatcgcattgtctgagtaggtgtcattctattctggggggt ggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctggggatgc ggtgggctctatgg 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 SCP1-CFI (mutant) 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)x4is independently selected from any of SEQ ID NOs: 16-28. In some embodiments, (n)x1is selected from any of SEQ ID NOs: 16- 28. In some embodiments, (n)x2is selected from any of SEQ ID NOs: 16-28. In some embodiments, (n)x3is selected from any of SEQ ID NOs: 16-28. In some embodiments, (n)x4is selected from any of SEQ ID NOs: 16-28. SCP1-CFH polynucleotide In some embodiments, the polynucleotide comprises: a 5’ ITR; a kidney-specific promoter; a super core promoter; a protein coding sequence encoding CFH; 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: 2; a super core promoter consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 5; a CFH coding sequence consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 37; optionally, a WPRE consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 51; 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: 2; a super core promoter consisting of a nucleotide sequence having at least 85% sequence identity to SEQ ID NO: 5; a CFH coding sequence consisting of a nucleotide sequence having at least 85% sequence identity to SEQ ID NO: 37; optionally, a WPRE consisting of a nucleotide sequence having at least 85% sequence identity to SEQ ID NO: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 85% sequence identity to SEQ ID NO: 51; 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: 2; a super core promoter consisting of a nucleotide sequence having at least 90% sequence identity to SEQ ID NO: 5; a CFH coding sequence consisting of a nucleotide sequence having at least 90% sequence identity to SEQ ID NO: 37; optionally, a WPRE consisting of a nucleotide sequence having at least 90% sequence identity to SEQ ID NO: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 90% sequence identity to SEQ ID NO: 51; 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: 2; a super core promoter consisting of a nucleotide sequence having at least 95% sequence identity to SEQ ID NO: 5; a CFH coding sequence consisting of a nucleotide sequence having at least 95% sequence identity to SEQ ID NO: 37; optionally, a WPRE consisting of a nucleotide sequence having at least 95% sequence identity to SEQ ID NO: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 95% sequence identity to SEQ ID NO: 51; 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: 2; a super core promoter consisting of a nucleotide sequence having at least 96% sequence identity to SEQ ID NO: 5; a CFH coding sequence consisting of a nucleotide sequence having at least 96% sequence identity to SEQ ID NO: 37; optionally, a WPRE consisting of a nucleotide sequence having at least 96% sequence identity to SEQ ID NO: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 96% sequence identity to SEQ ID NO: 51; 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: 2; a super core promoter consisting of a nucleotide sequence having at least 97% sequence identity to SEQ ID NO: 5; a CFH coding sequence consisting of a nucleotide sequence having at least 97% sequence identity to SEQ ID NO: 37; optionally, a WPRE consisting of a nucleotide sequence having at least 97% sequence identity to SEQ ID NO: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 97% sequence identity to SEQ ID NO: 51; 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: 2; a super core promoter consisting of a nucleotide sequence having at least 98% sequence identity to SEQ ID NO: 5; a CFH coding sequence consisting of a nucleotide sequence having at least 98% sequence identity to SEQ ID NO: 37; optionally, a WPRE consisting of a nucleotide sequence having at least 98% sequence identity to SEQ ID NO: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 98% sequence identity to SEQ ID NO: 51; 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: 2; a super core promoter consisting of a nucleotide sequence having at least 99% sequence identity to SEQ ID NO: 5; a CFH coding sequence consisting of a nucleotide sequence having at least 99% sequence identity to SEQ ID NO: 37; optionally, a WPRE consisting of a nucleotide sequence having at least 99% sequence identity to SEQ ID NO: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 99% sequence identity to SEQ ID NO: 51; 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: 2; a super core promoter consisting of the nucleotide sequence of SEQ ID NO: 5; a CFH coding sequence consisting of the nucleotide sequence of SEQ ID NO: 37; optionally, a WPRE consisting of the nucleotide sequence of SEQ ID NO: 50; optionally, a polyadenylation sequence consisting of the nucleotide sequence of SEQ ID NO: 51; and a 3’ ITR. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 70% identical to SEQ ID NO: 55. 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: 55. In some embodiments, the polynucleotide comprises the nucleotide sequence SEQ ID NO: 55. ggccctggggtcacggaggctggggaggcaccgaggaacgcgcctggcatgtgctgacaggg gattttatgctccaggagcaagacagagagagatactcacagggaagaggggaagaggaaaa cgagaaagggaggagagtaacggaaagagataaaaaagaaaagcaggtggcagagacacaca gagagggacccagagaaagccagacagacgcaggtggctggcagcgggcgctgtgggggtca cagtagggggacctgtg(n) gtacttatataagggggtgggggcgcgttcgtcctcagtcg cgatcgaacactcgagccgagcagacgtgcctacggaccg(n) atgaggctgctggcaaag attatctgtctcatgctgtgggctatttgcgtggccgaggactgcaacgagctgcctccaag gagaaataccgagatcctgaccggaagctggagcgaccagacctaccccgagggcacccagg ccatctataagtgccggcccggctacaggtccctggggaacgtgatcatggtgtgccggaag ggagagtgggtggccctgaaccctctgagaaaatgccagaagaggccctgcggccaccccgg agatactccctttgggaccttcacactgaccggcggcaacgtcttcgagtacggcgtgaaag ccgtgtatacttgcaatgaaggctatcagctgctgggagaaattaactacagggagtgcgac accgatggctggaccaatgacattcccatctgcgaagtggtgaagtgcctgcctgtgaccgc tcccgaaaacggcaaaattgtgtccagcgccatggagcccgaccgggagtatcacttcggac aggccgtgaggttcgtgtgcaattccggatataagatcgagggggacgaagagatgcactgc tccgacgatggcttctggtccaaggagaagcccaagtgtgtggagatcagctgtaagagccc agacgtgatcaacggctcccctatctcacagaagattatctataaagagaatgaacgctttc agtacaagtgtaacatgggctatgagtattccgagaggggcgatgccgtgtgtaccgagagc ggatggaggcccctgccttcctgcgaggagaagtcatgtgacaatccttacatccctaacgg cgattactctcccctgcgcatcaagcacagaactggggatgagattacctatcagtgccgga atggcttctaccctgccacaagaggcaacactgcaaagtgtacatctacaggctggatcccc gcccccagatgcaccctgaagccctgcgactatcccgacatcaaacacggaggattgtacca cgagaacatgcgtcggccttatttccccgtggccgtgggaaagtactactcctactattgcg acgagcactttgagactcctagcggaagctattgggatcatatccactgcacccaggacgga tggtctccagccgtgccttgtctgagaaagtgctactttccatacctcgagaatggctacaa tcagaatcatggcagaaagttcgtgcagggaaagagcattgacgttgcctgccaccctggct acgccctgcctaaggcccagaccacagtgacctgtatggagaatggctggagccccacccca aggtgcatcagagtcaagacatgctctaagtcctccatcgacatcgagaacgggtttatctc tgaatcccagtatacatatgccctcaaggaaaaagccaagtatcagtgcaagctcggctacg tgaccgctgacggcgaaacaagcggcagtatcacatgtggcaaggatggctggtcagcccag cctacctgtatcaagagctgcgacatcccagtgtttatgaacgccaggaccaaaaacgactt cacatggttcaaactgaacgacacactggactacgagtgtcacgacggctatgagtctaaca ccggctccactacaggaagcatcgtgtgtggttataacggatggtccgatctgcccatctgc tatgagagagagtgcgagctgcccaagatcgatgtccacctagtgccagacagaaagaagga tcagtacaaggtcggcgaggtgctgaagttcagttgtaaacccggcttcactattgtggggc ccaactccgtgcaatgctatcactttggcctgagccctgacctgcccatctgtaaggagcag gtgcagagctgcggccctccccccgagctgctgaatgggaatgtgaaggagaagaccaagga ggaatacggccactccgaggtggtggagtattactgcaaccctcgctttctcatgaaaggcc ccaacaagatccagtgcgtcgatggcgagtggaccaccctgcccgtgtgtattgtcgaggag agtacctgcggcgatatccctgaactggagcacgggtgggcccagctgtcctcccccccata ctactacggggactccgtggagttcaactgcagcgagtccttcaccatgattggacatcgga gtatcacctgtatccacggcgtatggactcagctgccacagtgcgtggccatcgataagctg aagaaatgtaagagcagtaacctgattatcctcgaagaacacctgaagaacaagaaggaatt tgatcataacagcaatatcaggtacagatgcaggggaaaggagggatggattcacacagtgt gcatcaatggccgctgggaccctgaggtcaattgcagcatggcccagatccagctgtgtcct ccaccaccccagatccccaatagccataacatgaccacaaccctgaattacagagatggcga aaaggtgagcgtgctgtgccaggagaactacctgatccaggagggcgaggaaataacctgta aggacggacggtggcagagcatccccctgtgcgtggagaagattccctgctcacagccccca cagatcgagcacggaacaatcaatagctccaggagcagccaggagtcttatgcccacggcac caagctgagctacacctgcgaggggggcttccggatcagcgaggaaaacgaaacaacatgct acatgggcaaatggagcagtcctcctcagtgtgagggcctgccatgtaaaagcccacctgag atcagtcacggcgtggtcgctcacatgagcgactcctaccagtatggcgaggaggtgacata taagtgcttcgagggctttggcatcgacggccccgctattgccaagtgcctgggagagaaat ggtcacacccaccttcttgcatcaagacagactgcctgagcctcccctctttcgagaatgca atccccatgggcgaaaaaaaggatgtgtacaaggccggcgagcaggtgacctatacctgcgc cacctactacaaaatggacggtgcctccaatgtgacctgtatcaattccaggtggactggca gaccaacctgccgggacactagctgcgtgaatccccccactgtgcagaatgcctatatcgtg agcagacagatgagcaagtacccatctggtgagcgggtgaggtaccagtgccggtccccata tgagatgtttggggacgaggaggtgatgtgtcttaacggaaactggactgaacctccccagt gtaaggacagtaccggcaagtgtgggccaccccctcccatcgacaacggcgatattacatcc tttccactgtcagtgtacgcccccgccagctccgtggagtaccagtgtcagaatctgtacca gctggagggcaacaagaggatcacctgtagaaacggccagtggagcgagccaccaaagtgcc tgcatccctgtgtgatcagcagggagatcatggagaattacaacatcgcactgcggtggacc gccaagcagaaactgtactcccgcacaggggagtccgtggagtttgtctgtaaacggggcta cagactgagttccagaagccacaccctgagaaccacctgttgggatgggaagctggaatatc ccacctgtgcaaagaga(n) aatcaacctctggattacaaaatttgtgaaagattgactgg tattcttaactatgttgctccttttacgctatgtggatacgctgctttaatgcctttgtatc atgctattgcttcccgtatggctttcattttctcctccttgtataaatcctggttgctgtct ctttatgaggagttgtggcccgttgtcaggcaacgtggcgtggtgtgcactgtgtttgctga cgcaacccccactggttggggcattgccaccacctgtcagctcctttccgggactttcgctt tccccctccctattgccacggcggaactcatcgccgcctgccttgcccgctgctggacaggg gctcggctgttgggcactgacaattccgtggtgttgtcggggaaatcatcgtcctttccttg gctgctcgcctgtgttgccacctggattctgcgcgggacgtccttctgctacgtcccttcgg ccctcaatccagcggaccttccttcccgcggcctgctgccggctctgcggcctcttccgcgt cttcgccttcgccctcagacgagtcggatctccctttgggccgcctccccgc(n) ctgtgc cttctagttgccagccatctgttgtttgcccctcccccgtgccttccttgaccctggaaggt gccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtaggtg tcattctattctggggggtggggtggggcaggacagcaagggggaggattgggaagacaata gcaggcatgctggggatgcggtgggctctatgg 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 SCP1-CFH polynucleotide (SEQ ID NO: 55) 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: 16-28. In some embodiments, (n)x1 is selected from any of SEQ ID NOs: 16- 28. In some embodiments, (n)x2 is selected from any of SEQ ID NOs: 16-28. In some embodiments, (n)x3 is selected from any of SEQ ID NOs: 16-28. In some embodiments, (n)x4 is selected from any of SEQ ID NOs: 16-28. SCP1-FHL1 polynucleotide In some embodiments, the polynucleotide comprises: a 5’ ITR; a kidney-specific promoter; a super core promoter; a protein coding sequence encoding FHL-1; 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: 2; a super core promoter consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 5; a FHL-1 coding sequence consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 39; optionally, a WPRE consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 51; 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: 2; a super core promoter consisting of a nucleotide sequence having at least 85% sequence identity to SEQ ID NO: 5; a FHL-1 coding sequence consisting of a nucleotide sequence having at least 85% sequence identity to SEQ ID NO: 39; optionally, a WPRE consisting of a nucleotide sequence having at least 85% sequence identity to SEQ ID NO: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 85% sequence identity to SEQ ID NO: 51; 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: 2; a super core promoter consisting of a nucleotide sequence having at least 90% sequence identity to SEQ ID NO: 5; a FHL-1 coding sequence consisting of a nucleotide sequence having at least 90% sequence identity to SEQ ID NO: 39; optionally, a WPRE consisting of a nucleotide sequence having at least 90% sequence identity to SEQ ID NO: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 90% sequence identity to SEQ ID NO: 51; 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: 2; a super core promoter consisting of a nucleotide sequence having at least 95% sequence identity to SEQ ID NO: 5; a FHL-1 coding sequence consisting of a nucleotide sequence having at least 95% sequence identity to SEQ ID NO: 39; optionally, a WPRE consisting of a nucleotide sequence having at least 95% sequence identity to SEQ ID NO: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 95% sequence identity to SEQ ID NO: 51; 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: 2; a super core promoter consisting of a nucleotide sequence having at least 96% sequence identity to SEQ ID NO: 5; a FHL-1 coding sequence consisting of a nucleotide sequence having at least 96% sequence identity to SEQ ID NO: 39; optionally, a WPRE consisting of a nucleotide sequence having at least 96% sequence identity to SEQ ID NO: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 96% sequence identity to SEQ ID NO: 51; 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: 2; a super core promoter consisting of a nucleotide sequence having at least 97% sequence identity to SEQ ID NO: 5; a FHL-1 coding sequence consisting of a nucleotide sequence having at least 97% sequence identity to SEQ ID NO: 39; optionally, a WPRE consisting of a nucleotide sequence having at least 97% sequence identity to SEQ ID NO: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 97% sequence identity to SEQ ID NO: 51; 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: 2; a super core promoter consisting of a nucleotide sequence having at least 98% sequence identity to SEQ ID NO: 5; a FHL-1 coding sequence consisting of a nucleotide sequence having at least 98% sequence identity to SEQ ID NO: 39; optionally, a WPRE consisting of a nucleotide sequence having at least 98% sequence identity to SEQ ID NO: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 98% sequence identity to SEQ ID NO: 51; 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: 2; a super core promoter consisting of a nucleotide sequence having at least 99% sequence identity to SEQ ID NO: 5; a FHL-1 coding sequence consisting of a nucleotide sequence having at least 99% sequence identity to SEQ ID NO: 39; optionally, a WPRE consisting of a nucleotide sequence having at least 99% sequence identity to SEQ ID NO: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 99% sequence identity to SEQ ID NO: 51; 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: 2; a super core promoter consisting of the nucleotide sequence of SEQ ID NO: 5; a FHL-1 coding sequence consisting of the nucleotide sequence of SEQ ID NO: 39; optionally, a WPRE consisting of the nucleotide sequence of SEQ ID NO: 50; optionally, a polyadenylation sequence consisting of the nucleotide sequence of SEQ ID NO: 51; and a 3’ ITR. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 70% identical to SEQ ID NO: 56. 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: 56. In some embodiments, the polynucleotide comprises the nucleotide sequence SEQ ID NO: 56. ggccctggggtcacggaggctggggaggcaccgaggaacgcgcctggcatgtgctgacaggg gattttatgctccaggagcaagacagagagagatactcacagggaagaggggaagaggaaaa cgagaaagggaggagagtaacggaaagagataaaaaagaaaagcaggtggcagagacacaca gagagggacccagagaaagccagacagacgcaggtggctggcagcgggcgctgtgggggtca cagtagggggacctgtg(n) gtacttatataagggggtgggggcgcgttcgtcctcagtcg cgatcgaacactcgagccgagcagacgtgcctacggaccg(n) atgcggctgctggccaaa atcatctgtctgatgctgtgggccatctgtgtggccgaggattgcaacgagctgccccctag acgcaatacagagatcctgacaggcagctggtccgaccagacataccctgagggaacccagg ccatctacaagtgcagaccaggatatcggtccctgggaaatgtgataatggtgtgtagaaag ggagagtgggtggctctgaaccctctgaggaaatgccagaagcgcccatgcggccaccccgg cgatacccccttcggcaccttcacactgaccggcggcaatgtgtttgagtatggcgtgaagg ccgtgtacacctgcaacgagggctaccagctgctgggtgagattaactaccgcgagtgtgat accgacggctggaccaacgacatccccatctgtgaagtggtgaagtgtctgcccgtgaccgc accagagaatggcaaaatcgtgagttctgccatggagcctgatagggagtaccactttggcc aggccgtgcgctttgtgtgtaattctggctacaagatcgagggcgacgaggagatgcattgc tctgacgatggcttctggtcaaaggaaaagcccaaatgcgtggagattagctgtaagtcccc agacgtcatcaacggctcccctatctctcagaagatcatttacaaggagaatgaacggtttc agtataaatgcaacatgggctacgagtactccgagcggggcgatgccgtgtgtaccgagtca gggtggcgaccactccctagttgtgaagagaagagctgcgacaatccctacatccccaacgg cgactactctccactgaggatcaagcacaggacaggcgacgagatcacctaccagtgccgca acgggttttaccctgccacaaggggcaatactgccaagtgcaccagcacagggtggattcct gccccccggtgtacactgaagccatgcgattacccagatatcaaacatgggggcctgtacca tgagaatatgaggcggccatactttcccgtggccgtgggcaagtactactcctactattgcg acgagcactttgagacaccctccggctcctactgggaccatatccactgtacccaggatggc tggtcccctgccgtgccatgtctgagaaaatgctacttcccctatctggagaacgggtacaa ccagaaccacgggaggaagttcgttcaggggaagtccattgacgtggcctgccatcccggct acgccctgcccaaggcccagactactgtgacctgcatggagaatggttggagccccaccccc cggtgtatccgggtgagctttaccctg(n) aatcaacctctggattacaaaatttgtgaaa gattgactggtattcttaactatgttgctccttttacgctatgtggatacgctgctttaatg cctttgtatcatgctattgcttcccgtatggctttcattttctcctccttgtataaatcctg gttgctgtctctttatgaggagttgtggcccgttgtcaggcaacgtggcgtggtgtgcactg tgtttgctgacgcaacccccactggttggggcattgccaccacctgtcagctcctttccggg actttcgctttccccctccctattgccacggcggaactcatcgccgcctgccttgcccgctg ctggacaggggctcggctgttgggcactgacaattccgtggtgttgtcggggaaatcatcgt cctttccttggctgctcgcctgtgttgccacctggattctgcgcgggacgtccttctgctac gtcccttcggccctcaatccagcggaccttccttcccgcggcctgctgccggctctgcggcc tcttccgcgtcttcgccttcgccctcagacgagtcggatctccctttgggccgcctccccgc (n) ctgtgccttctagttgccagccatctgttgtttgcccctcccccgtgccttccttgac cctggaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtc tgagtaggtgtcattctattctggggggtggggtggggcaggacagcaagggggaggattgg gaagacaatagcaggcatgctggggatgcggtgggctctatgg 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 SCP1-FHL1 polynucleotide (SEQ ID NO: 56) 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)x4is independently selected from any of SEQ ID NOs: 16-28. In some embodiments, (n)x1is selected from any of SEQ ID NOs: 16- 28. In some embodiments, (n)x2is selected from any of SEQ ID NOs: 16-28. In some embodiments, (n)x3is selected from any of SEQ ID NOs: 16-28. In some embodiments, (n)x4is selected from any of SEQ ID NOs: 16-28. SCP1-bicistronic polynucleotide In some embodiments, the polynucleotide comprises: a 5’ ITR; a kidney-specific promoter; a super core promoter; a protein coding sequence encoding CFI and FHL-1; 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: 2; a super core promoter consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 5; a protein coding sequence encoding CFI and FHL-1 and consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 47 or 49; optionally, a WPRE consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 51; 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: 2; a super core promoter consisting of a nucleotide sequence having at least 85% sequence identity to SEQ ID NO: 5; a protein coding sequence encoding CFI and FHL-1 and consisting of a nucleotide sequence having at least 85% sequence identity to SEQ ID NO: 47 or 49; optionally, a WPRE consisting of a nucleotide sequence having at least 85% sequence identity to SEQ ID NO: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 85% sequence identity to SEQ ID NO: 51; 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: 2; a super core promoter consisting of a nucleotide sequence having at least 90% sequence identity to SEQ ID NO: 5; a protein coding sequence encoding CFI and FHL-1 and consisting of a nucleotide sequence having at least 90% sequence identity to SEQ ID NO: 47 or 49; optionally, a WPRE consisting of a nucleotide sequence having at least 90% sequence identity to SEQ ID NO: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 90% sequence identity to SEQ ID NO: 51; 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: 2; a super core promoter consisting of a nucleotide sequence having at least 95% sequence identity to SEQ ID NO: 5; a protein coding sequence encoding CFI and FHL-1 and consisting of a nucleotide sequence having at least 95% sequence identity to SEQ ID NO: 47 or 49; optionally, a WPRE consisting of a nucleotide sequence having at least 95% sequence identity to SEQ ID NO: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 95% sequence identity to SEQ ID NO: 51; 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: 2; a super core promoter consisting of a nucleotide sequence having at least 96% sequence identity to SEQ ID NO: 5; a protein coding sequence encoding CFI and FHL-1 and consisting of a nucleotide sequence having at least 96% sequence identity to SEQ ID NO: 47 or 49; optionally, a WPRE consisting of a nucleotide sequence having at least 96% sequence identity to SEQ ID NO: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 96% sequence identity to SEQ ID NO: 51; 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: 2; a super core promoter consisting of a nucleotide sequence having at least 97% sequence identity to SEQ ID NO: 5; a protein coding sequence encoding CFI and FHL-1 and consisting of a nucleotide sequence having at least 97% sequence identity to SEQ ID NO: 47 or 49; optionally, a WPRE consisting of a nucleotide sequence having at least 97% sequence identity to SEQ ID NO: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 97% sequence identity to SEQ ID NO: 51; 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: 2; a super core promoter consisting of a nucleotide sequence having at least 98% sequence identity to SEQ ID NO: 5; a protein coding sequence encoding CFI and FHL-1 and consisting of a nucleotide sequence having at least 98% sequence identity to SEQ ID NO: 47 or 49; optionally, a WPRE consisting of a nucleotide sequence having at least 98% sequence identity to SEQ ID NO: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 98% sequence identity to SEQ ID NO: 51; 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: 2; a super core promoter consisting of a nucleotide sequence having at least 99% sequence identity to SEQ ID NO: 5; a protein coding sequence encoding CFI and FHL-1 and consisting of a nucleotide sequence having at least 99% sequence identity to SEQ ID NO: 47 or 49; optionally, a WPRE consisting of a nucleotide sequence having at least 99% sequence identity to SEQ ID NO: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 99% sequence identity to SEQ ID NO: 51; 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: 2; a super core promoter consisting of the nucleotide sequence of SEQ ID NO: 5; a protein coding sequence encoding CFI and FHL- 1 and consisting of the nucleotide sequence of SEQ ID NO: 47 or 49; optionally, a WPRE consisting of the nucleotide sequence of SEQ ID NO: 50; optionally, a polyadenylation sequence consisting of the nucleotide sequence of SEQ ID NO: 51; and a 3’ ITR. SCP1-CFI-FHL1 In some embodiments, the polynucleotide comprises: a 5’ ITR; a kidney-specific promoter; a super core promoter; a protein coding sequence encoding from 5’ to 3’: CFI, a 2A self-cleaving peptide, and FHL-1; 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: 2; a super core promoter consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 5; a protein coding sequence encoding from 5’ to 3’: CFI, a 2A self- cleaving peptide, and FHL-1 and consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 47; optionally, a WPRE consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 51; 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: 2; a super core promoter consisting of a nucleotide sequence having at least 85% sequence identity to SEQ ID NO: 5; a protein coding sequence encoding from 5’ to 3’: CFI, a 2A self- cleaving peptide, and FHL-1 and consisting of a nucleotide sequence having at least 85% sequence identity to SEQ ID NO: 47; optionally, a WPRE consisting of a nucleotide sequence having at least 85% sequence identity to SEQ ID NO: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 85% sequence identity to SEQ ID NO: 51; 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: 2; a super core promoter consisting of a nucleotide sequence having at least 90% sequence identity to SEQ ID NO: 5; a protein coding sequence encoding from 5’ to 3’: CFI, a 2A self- cleaving peptide, and FHL-1 and consisting of a nucleotide sequence having at least 90% sequence identity to SEQ ID NO: 47; optionally, a WPRE consisting of a nucleotide sequence having at least 90% sequence identity to SEQ ID NO: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 90% sequence identity to SEQ ID NO: 51; 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: 2; a super core promoter consisting of a nucleotide sequence having at least 95% sequence identity to SEQ ID NO: 5; a protein coding sequence encoding from 5’ to 3’: CFI, a 2A self- cleaving peptide, and FHL-1 and consisting of a nucleotide sequence having at least 95% sequence identity to SEQ ID NO: 47; optionally, a WPRE consisting of a nucleotide sequence having at least 95% sequence identity to SEQ ID NO: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 95% sequence identity to SEQ ID NO: 51; 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: 2; a super core promoter consisting of a nucleotide sequence having at least 96% sequence identity to SEQ ID NO: 5; a protein coding sequence encoding from 5’ to 3’: CFI, a 2A self- cleaving peptide, and FHL-1 and consisting of a nucleotide sequence having at least 96% sequence identity to SEQ ID NO: 47; optionally, a WPRE consisting of a nucleotide sequence having at least 96% sequence identity to SEQ ID NO: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 96% sequence identity to SEQ ID NO: 51; 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: 2; a super core promoter consisting of a nucleotide sequence having at least 97% sequence identity to SEQ ID NO: 5; a protein coding sequence encoding from 5’ to 3’: CFI, a 2A self- cleaving peptide, and FHL-1 and consisting of a nucleotide sequence having at least 97% sequence identity to SEQ ID NO: 47; optionally, a WPRE consisting of a nucleotide sequence having at least 97% sequence identity to SEQ ID NO: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 97% sequence identity to SEQ ID NO: 51; 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: 2; a super core promoter consisting of a nucleotide sequence having at least 98% sequence identity to SEQ ID NO: 5; a protein coding sequence encoding from 5’ to 3’: CFI, a 2A self- cleaving peptide, and FHL-1 and consisting of a nucleotide sequence having at least 98% sequence identity to SEQ ID NO: 47; optionally, a WPRE consisting of a nucleotide sequence having at least 98% sequence identity to SEQ ID NO: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 98% sequence identity to SEQ ID NO: 51; 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: 2; a super core promoter consisting of a nucleotide sequence having at least 99% sequence identity to SEQ ID NO: 5; a protein coding sequence encoding from 5’ to 3’: CFI, a 2A self- cleaving peptide, and FHL-1 and consisting of a nucleotide sequence having at least 99% sequence identity to SEQ ID NO: 47; optionally, a WPRE consisting of a nucleotide sequence having at least 99% sequence identity to SEQ ID NO: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 99% sequence identity to SEQ ID NO: 51; 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: 2; a super core promoter consisting of the nucleotide sequence of SEQ ID NO: 5; a protein coding sequence encoding from 5’ to 3’: CFI, a 2A self-cleaving peptide, and FHL-1 and consisting of the nucleotide sequence of SEQ ID NO: 47; optionally, a WPRE consisting of the nucleotide sequence of SEQ ID NO: 50; optionally, a polyadenylation sequence consisting of the nucleotide sequence of SEQ ID NO: 51; and a 3’ ITR. In some embodiments, the polynucleotide comprises a nucleotide sequence which is at least 70% identical to SEQ ID NO: 57. 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: 57. In some embodiments, the polynucleotide comprises the nucleotide sequence SEQ ID NO: 57. ggccctggggtcacggaggctggggaggcaccgaggaacgcgcctggcatgtgctgacaggg gattttatgctccaggagcaagacagagagagatactcacagggaagaggggaagaggaaaa cgagaaagggaggagagtaacggaaagagataaaaaagaaaagcaggtggcagagacacaca gagagggacccagagaaagccagacagacgcaggtggctggcagcgggcgctgtgggggtca cagtagggggacctgtg(n) gtacttatataagggggtgggggcgcgttcgtcctcagtcg cgatcgaacactcgagccgagcagacgtgcctacggaccg(n) atgaagctgctgcatgtg ttcctgttgttcctgtgttttcacctgagattttgtaaggtgacttataccagccaggaaga cctggtagagaagaagtgcctggccaagaagtatactcacctgtcttgcgataaggtgttct gccagccttggcagcggtgcatcgagggcacctgtgtgtgcaagctgccctatcagtgtccc aagaatgggaccgccgtgtgtgccaccaacagaaggagcttccccacctattgccagcagaa gagcctggagtgtctgcaccccggcaccaagttcctgaataatggcacatgtaccgccgagg gcaagttctcagtctccctgaagcatggcaacactgacagtgagggcatcgtggaggtgaaa ctggtggaccaggacaagacaatgttcatctgtaagtcatcttggtctatgcgggaggccaa cgtggcctgcctggatctgggcttccagcagggggccgatacccagaggcgattcaagctga gcgatctgtctataaacagcaccgagtgcctgcacgtgcactgcaggggcctggaaacctct ctggccgaatgcaccttcaccaagagacggactatgggctaccaggattttgccgatgtggt gtgctatacccagaaagccgactcccccatggacgacttcttccaatgtgtcaatggaaagt acatcagtcagatgaaggcatgtgacggcattaacgattgtggcgatcagagcgatgagctg tgctgtaaggcctgccagggaaagggcttccactgcaaatccggcgtgtgcatccctagcca gtaccagtgtaatggcgaggtggactgtatcacaggagaggacgaagtgggatgcgctggat tcgctagtgtgacccaggaggagaccgagatcctgaccgccgacatggatgccgagaggaga cgtatcaagtccctgctgcctaagctgtcttgtggagtgaagaataggatgcacatcagacg caagagaatcgtcggcggcaagcgcgcccagctgggcgatctgccctggcaagtggccatta aggacgcctccggcatcacatgtggaggaatatacataggcgggtgctggatcctgaccgcc gcccactgcctgcgggcctctaaaactcataggtaccagatctggacaaccgtggtggattg gatccatcctgatctgaagagaatcgtgatcgagtacgtcgataggattatctttcacgaga actataatgccgggacctaccagaatgacatcgctctcattgagatgaagaaggatggcaac aagaaggactgcgagctgcccaggagcattcccgcttgcgtgccatggtccccatacctgtt ccagccaaacgacacctgcatcgtgagcggctggggcagagaaaaggacaacgagagagtgt tctccctgcagtggggcgaagtgaagctgatttccaactgcagtaagttctacggcaaccgc ttctatgagaaggagatggagtgtgccggcacatacgacggcagcatcgacgcctgcaaggg cgacagcggcggccccctggtgtgcatggacgccaacaacgtgacctatgtgtggggggtgg tgtcctggggcgagaactgtggaaagccagagttccctggagtgtataccaaggtggccaac tacttcgattggatcagctaccacgtcggcaggcccttcatcagccagtacaacgttggaag cggagctactaacttcagcctgctgaagcaggctggcgacgtggaggagaaccctggaccta tgcggctgctggccaaaatcatctgtctgatgctgtgggccatctgtgtggccgaggattgc aacgagctgccccctagacgcaatacagagatcctgacaggcagctggtccgaccagacata ccctgagggaacccaggccatctacaagtgcagaccaggatatcggtccctgggaaatgtga taatggtgtgtagaaagggagagtgggtggctctgaaccctctgaggaaatgccagaagcgc ccatgcggccaccccggcgatacccccttcggcaccttcacactgaccggcggcaatgtgtt tgagtatggcgtgaaggccgtgtacacctgcaacgagggctaccagctgctgggtgagatta actaccgcgagtgtgataccgacggctggaccaacgacatccccatctgtgaagtggtgaag tgtctgcccgtgaccgcaccagagaatggcaaaatcgtgagttctgccatggagcctgatag ggagtaccactttggccaggccgtgcgctttgtgtgtaattctggctacaagatcgagggcg acgaggagatgcattgctctgacgatggcttctggtcaaaggaaaagcccaaatgcgtggag attagctgtaagtccccagacgtcatcaacggctcccctatctctcagaagatcatttacaa ggagaatgaacggtttcagtataaatgcaacatgggctacgagtactccgagcggggcgatg ccgtgtgtaccgagtcagggtggcgaccactccctagttgtgaagagaagagctgcgacaat ccctacatccccaacggcgactactctccactgaggatcaagcacaggacaggcgacgagat cacctaccagtgccgcaacgggttttaccctgccacaaggggcaatactgccaagtgcacca gcacagggtggattcctgccccccggtgtacactgaagccatgcgattacccagatatcaaa catgggggcctgtaccatgagaatatgaggcggccatactttcccgtggccgtgggcaagta ctactcctactattgcgacgagcactttgagacaccctccggctcctactgggaccatatcc actgtacccaggatggctggtcccctgccgtgccatgtctgagaaaatgctacttcccctat ctggagaacgggtacaaccagaaccacgggaggaagttcgttcaggggaagtccattgacgt ggcctgccatcccggctacgccctgcccaaggcccagactactgtgacctgcatggagaatg gttggagccccaccccccggtgtatccgggtgagctttaccctg(n) aatcaacctctgga ttacaaaatttgtgaaagattgactggtattcttaactatgttgctccttttacgctatgtg gatacgctgctttaatgcctttgtatcatgctattgcttcccgtatggctttcattttctcc tccttgtataaatcctggttgctgtctctttatgaggagttgtggcccgttgtcaggcaacg tggcgtggtgtgcactgtgtttgctgacgcaacccccactggttggggcattgccaccacct gtcagctcctttccgggactttcgctttccccctccctattgccacggcggaactcatcgcc gcctgccttgcccgctgctggacaggggctcggctgttgggcactgacaattccgtggtgtt gtcggggaaatcatcgtcctttccttggctgctcgcctgtgttgccacctggattctgcgcg ggacgtccttctgctacgtcccttcggccctcaatccagcggaccttccttcccgcggcctg ctgccggctctgcggcctcttccgcgtcttcgccttcgccctcagacgagtcggatctccct ttgggccgcctccccgc(n) ctgtgccttctagttgccagccatctgttgtttgcccctcc cccgtgccttccttgaccctggaaggtgccactcccactgtcctttcctaataaaatgagga aattgcatcgcattgtctgagtaggtgtcattctattctggggggtggggtggggcaggaca gcaagggggaggattgggaagacaatagcaggcatgctggggatgcggtgggctctatgg 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 SCP1-CFI-FHL1 polynucleotide (SEQ ID NO: 57) 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)x4is independently selected from any of SEQ ID NOs: 16-28. In some embodiments, (n)x1is selected from any of SEQ ID NOs: 16- 28. In some embodiments, (n)x2is selected from any of SEQ ID NOs: 16-28. In some embodiments, (n)x3is selected from any of SEQ ID NOs: 16-28. In some embodiments, (n)x4is selected from any of SEQ ID NOs: 16-28. SCP1-FHL1-CFI In some embodiments, the polynucleotide comprises: a 5’ ITR; a kidney-specific promoter; a super core promoter; a protein coding sequence encoding from 5’ to 3’: FHL-1, a 2A self- cleaving peptide, and CFI; 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: 2; a super core promoter consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 5; a protein coding sequence encoding from 5’ to 3’: FHL-1, a 2A self- cleaving peptide, and CFI and consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 49; optionally, a WPRE consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 51; 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: 2; a super core promoter consisting of a nucleotide sequence having at least 85% sequence identity to SEQ ID NO: 5; a protein coding sequence encoding from 5’ to 3’: FHL-1, a 2A self- cleaving peptide, and CFI and consisting of a nucleotide sequence having at least 85% sequence identity to SEQ ID NO: 49; optionally, a WPRE consisting of a nucleotide sequence having at least 85% sequence identity to SEQ ID NO: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 85% sequence identity to SEQ ID NO: 51; 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: 2; a super core promoter consisting of a nucleotide sequence having at least 90% sequence identity to SEQ ID NO: 5; a protein coding sequence encoding from 5’ to 3’: FHL-1, a 2A self- cleaving peptide, and CFI and consisting of a nucleotide sequence having at least 90% sequence identity to SEQ ID NO: 49; optionally, a WPRE consisting of a nucleotide sequence having at least 90% sequence identity to SEQ ID NO: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 90% sequence identity to SEQ ID NO: 51; 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: 2; a super core promoter consisting of a nucleotide sequence having at least 95% sequence identity to SEQ ID NO: 5; a protein coding sequence encoding from 5’ to 3’: FHL-1, a 2A self- cleaving peptide, and CFI and consisting of a nucleotide sequence having at least 95% sequence identity to SEQ ID NO: 49; optionally, a WPRE consisting of a nucleotide sequence having at least 95% sequence identity to SEQ ID NO: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 95% sequence identity to SEQ ID NO: 51; 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: 2; a super core promoter consisting of a nucleotide sequence having at least 96% sequence identity to SEQ ID NO: 5; a protein coding sequence encoding from 5’ to 3’: FHL-1, a 2A self- cleaving peptide, and CFI and consisting of a nucleotide sequence having at least 96% sequence identity to SEQ ID NO: 49; optionally, a WPRE consisting of a nucleotide sequence having at least 96% sequence identity to SEQ ID NO: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 96% sequence identity to SEQ ID NO: 51; 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: 2; a super core promoter consisting of a nucleotide sequence having at least 97% sequence identity to SEQ ID NO: 5; a protein coding sequence encoding from 5’ to 3’: FHL-1, a 2A self- cleaving peptide, and CFI and consisting of a nucleotide sequence having at least 97% sequence identity to SEQ ID NO: 49; optionally, a WPRE consisting of a nucleotide sequence having at least 97% sequence identity to SEQ ID NO: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 97% sequence identity to SEQ ID NO: 51; 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: 2; a super core promoter consisting of a nucleotide sequence having at least 98% sequence identity to SEQ ID NO: 5; a protein coding sequence encoding from 5’ to 3’: FHL-1, a 2A self- cleaving peptide, and CFI and consisting of a nucleotide sequence having at least 98% sequence identity to SEQ ID NO: 49; optionally, a WPRE consisting of a nucleotide sequence having at least 98% sequence identity to SEQ ID NO: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence...

Claims

CLAIMS 1. A polynucleotide comprising: a 5’ ITR; a kidney-specific promoter; a regulatory element, wherein the regulatory element comprises a super core promoter, or 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 CFI, CFH, or FHL-1; and a 3’ ITR.

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

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

4. The polynucleotide according to any preceding claim, 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:

2.

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

2.

6. The polynucleotide according to any preceding claim, wherein the super core promoter is the super core promoter 1.

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:

5.

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

5.

9. 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.

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

11. The polynucleotide according to any of claims 1 to 6, wherein the regulatory element 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:

15.

12. The polynucleotide according to any of claims 1 to 6, wherein the regulatory element consists of the nucleotide sequence of SEQ ID NO:

15.

13. The polynucleotide according to any preceding claim, wherein the protein coding sequence encodes CFI.

14. 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:

31.

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

31.

16. 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:

33.

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

33.

18. The polynucleotide according to any of claims 1 to 15, 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:

34.

19. The polynucleotide according to any of claims 1 to 15, wherein the protein coding sequence comprises or consists of the nucleotide sequence of SEQ ID NO:

34.

20. The polynucleotide according to any of claims 1 to 15, 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: 35.

21. The polynucleotide according to any of claims 1 to 15, wherein the protein coding sequence comprises or consists of the nucleotide sequence of SEQ ID NO:

35.

22. The polynucleotide according to any preceding claim, wherein the protein coding sequence encodes CFH.

23. 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:

36.

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

36.

25. 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:

37.

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

37.

27. The polynucleotide according to any preceding claim, wherein the protein coding sequence encodes FHL-1.

28. 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:

38.

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

38.

30. 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:

39.

31. The polynucleotide according to any preceding claim, wherein the protein coding sequence comprises or consists of the nucleotide sequence of SEQ ID NO: 39.

32. The polynucleotide according to any preceding claim, wherein the protein coding sequence encodes CFI and FHL-1.

33. The polynucleotide according to claim 32, wherein the nucleotide sequences encoding CFI and FHL-1 are linked by a nucleotide sequence encoding a 2A self-cleaving peptide.

34. The polynucleotide according to claim 33, wherein the 2A self-cleaving peptide consists of the amino acid sequence of SEQ ID NO:

44.

35. The polynucleotide according to claim 33 or 34, wherein the nucleotide encoding a 2A self- cleaving peptide 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:

45.

36. The polynucleotide according to any of claims 33 to 35, wherein the nucleotide encoding a 2A self-cleaving peptide consists of the nucleotide sequence of SEQ ID NO:

45.

37. 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:

47.

38. 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:

49.

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

40. The polynucleotide according to claim 39, 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: 50, preferably wherein the WPRE consists of the nucleotide sequence of SEQ ID NO:

50.

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

42. The polynucleotide according to claim 41, wherein the polyadenylation sequence is a bovine growth hormone (bGH) polyadenylation sequence.

43. The polynucleotide according to claim 41 or 42, wherein 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: 51, preferably wherein the polyadenylation sequence consists of the nucleotide sequence of SEQ ID NO:

51.

44. The polynucleotide according to any preceding claim, wherein the 5’ ITR is an AAV25’ ITR.

45. 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: 82, preferably wherein the 5’ ITR consists of the nucleotide sequence of SEQ ID NO:

82.

46. The polynucleotide according to any preceding claim, wherein the 3’ ITR is an AAV23’ ITR.

47. 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: 83, preferably wherein the 3’ ITR consists of the nucleotide sequence of SEQ ID NO:

83.

48. 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, wherein the regulatory element comprises a super core promoter, or 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 a complement inhibitor; optionally, a WPRE; optionally, a polyadenylation sequence; and a 3’ ITR.

49. A polynucleotide comprising: a 5’ ITR; a kidney-specific promoter; a super core promoter; a protein coding sequence encoding CFI; optionally, a Woodchuck Hepatitis Virus Post- transcriptional Regulatory Element (WPRE); optionally, a polyadenylation sequence; and a 3’ ITR.

50. The polynucleotide according to claim 49, 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: 2; a super core promoter consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 5; a CFI coding sequence consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 33; 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: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 51; and a 3’ ITR.

51. The polynucleotide according to claim 49 or 50, comprising: a 5’ ITR; a kidney-specific promoter consisting of the nucleotide sequence of SEQ ID NO: 2; a super core promoter consisting of the nucleotide sequence of SEQ ID NO: 5; a CFI coding sequence consisting of the nucleotide sequence of SEQ ID NO: 33; optionally, a Woodchuck Hepatitis Virus Post- transcriptional Regulatory Element (WPRE) consisting of the nucleotide sequence of SEQ ID NO: 50; optionally, a polyadenylation sequence consisting of the nucleotide sequence of SEQ ID NO: 51; and a 3’ ITR.

52. The polynucleotide according to any of claims 49 to 51, wherein the polynucleotide comprises a nucleotide sequence which is at least 90% identical to SEQ ID NO:

52.

53. The polynucleotide according to claim 49, 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: 2; a super core promoter consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 5; a CFI coding sequence consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 34; 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: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 51; and a 3’ ITR.

54. The polynucleotide according to claim 49 or 53, comprising: a 5’ ITR; a kidney-specific promoter consisting of the nucleotide sequence of SEQ ID NO: 2; a super core promoter consisting of the nucleotide sequence of SEQ ID NO: 5; a CFI coding sequence consisting of the nucleotide sequence of SEQ ID NO: 34; optionally, a Woodchuck Hepatitis Virus Post- transcriptional Regulatory Element (WPRE) consisting of the nucleotide sequence of SEQ ID NO: 50; optionally, a polyadenylation sequence consisting of the nucleotide sequence of SEQ ID NO: 51; and a 3’ ITR.

55. The polynucleotide according to any of claims 49, 53 or 54, wherein the polynucleotide comprises a nucleotide sequence which is at least 90% identical to SEQ ID NO:

53.

56. The polynucleotide according to claim 49, 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: 2; a super core promoter consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 5; a CFI coding sequence consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 35; 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: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 51; and a 3’ ITR.

57. The polynucleotide according to claim 49 or 56, comprising: a 5’ ITR; a kidney-specific promoter consisting of the nucleotide sequence of SEQ ID NO: 2; a super core promoter consisting of the nucleotide sequence of SEQ ID NO: 5; a CFI coding sequence consisting of the nucleotide sequence of SEQ ID NO: 35; optionally, a Woodchuck Hepatitis Virus Post- transcriptional Regulatory Element (WPRE) consisting of the nucleotide sequence of SEQ ID NO: 50; optionally, a polyadenylation sequence consisting of the nucleotide sequence of SEQ ID NO: 51; and a 3’ ITR.

58. The polynucleotide according to any of claims 49, 56 or 57, wherein the polynucleotide comprises a nucleotide sequence which is at least 90% identical to SEQ ID NO:

54.

59. A polynucleotide comprising: a 5’ ITR; a kidney-specific promoter; a super core promoter; a protein coding sequence encoding CFH; optionally, a Woodchuck Hepatitis Virus Post- transcriptional Regulatory Element (WPRE); optionally, a polyadenylation sequence; and a 3’ ITR.

60. The polynucleotide according to claim 59, 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: 2; a super core promoter consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 5; a CFH coding sequence consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 37; 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: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 51; and a 3’ ITR.

61. The polynucleotide according to claim 59 or 60, comprising: a 5’ ITR; a kidney-specific promoter consisting of the nucleotide sequence of SEQ ID NO: 2; a super core promoter consisting of the nucleotide sequence of SEQ ID NO: 5; a CFH coding sequence consisting of the nucleotide sequence of SEQ ID NO: 37; optionally, a Woodchuck Hepatitis Virus Post- transcriptional Regulatory Element (WPRE) consisting of the nucleotide sequence of SEQ ID NO: 50; optionally, a polyadenylation sequence consisting of the nucleotide sequence of SEQ ID NO: 51; and a 3’ ITR.

62. The polynucleotide according to any of claims 59 to 61, wherein the polynucleotide comprises a nucleotide sequence which is at least 90% identical to SEQ ID NO:

55.

63. A polynucleotide comprising: a 5’ ITR; a kidney-specific promoter; a super core promoter; a protein coding sequence encoding FHL-1; optionally, a Woodchuck Hepatitis Virus Post- transcriptional Regulatory Element (WPRE); optionally, a polyadenylation sequence; and a 3’ ITR.

64. The polynucleotide according to claim 63, 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: 2; a super core promoter consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 5; a FHL-1 coding sequence consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 39; 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: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 51; and a 3’ ITR.

65. The polynucleotide according to claim 63 or 64, comprising: a 5’ ITR; a kidney-specific promoter consisting of the nucleotide sequence of SEQ ID NO: 2; a super core promoter consisting of the nucleotide sequence of SEQ ID NO: 5; a FHL-1 coding sequence consisting of the nucleotide sequence of SEQ ID NO: 39; optionally, a Woodchuck Hepatitis Virus Post- transcriptional Regulatory Element (WPRE) consisting of the nucleotide sequence of SEQ ID NO: 50; optionally, a polyadenylation sequence consisting of the nucleotide sequence of SEQ ID NO: 51; and a 3’ ITR.

66. The polynucleotide according to any of claims 63 to 65, wherein the polynucleotide comprises a nucleotide sequence which is at least 90% identical to SEQ ID NO:

56.

67. A polynucleotide comprising: a 5’ ITR; a kidney-specific promoter; a super core promoter; a protein coding sequence encoding CFI and FHL-1; optionally, a Woodchuck Hepatitis VirusPost-transcriptional Regulatory Element (WPRE); optionally, a polyadenylation sequence; and a 3’ ITR.

68. The polynucleotide according to claim 67, wherein the protein coding sequence encodes from 5’ to 3’: CFI; a 2A self-cleaving peptide; and FHL-1.

69. The polynucleotide according to claim 68, 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: 2; a super core promoter consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 5; a protein coding sequence consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 47; 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: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 51; and a 3’ ITR.

70. The polynucleotide according to claim 68 or 69, comprising: a 5’ ITR; a kidney-specific promoter consisting of the nucleotide sequence of SEQ ID NO: 2; a super core promoter consisting of the nucleotide sequence of SEQ ID NO: 5; a protein coding sequence consisting of the nucleotide sequence of SEQ ID NO: 47; optionally, a Woodchuck Hepatitis Virus Post- transcriptional Regulatory Element (WPRE) consisting of the nucleotide sequence of SEQ ID NO: 50; optionally, a polyadenylation sequence consisting of the nucleotide sequence of SEQ ID NO: 51; and a 3’ ITR.

71. The polynucleotide according to any of claims 68 to 70, wherein the polynucleotide comprises a nucleotide sequence which is at least 90% identical to SEQ ID NO:

57.

72. The polynucleotide according to claim 67, wherein the protein coding sequence encodes from 5’ to 3’: FHL-1; a 2A self-cleaving peptide; and CFI.

73. The polynucleotide according to claim 72, 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: 2; a super core promoter consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 5; a protein coding sequence consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 49; 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: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 51; and a 3’ ITR.

74. The polynucleotide according to claim 72 or 73, comprising: a 5’ ITR; a kidney-specific promoter consisting of the nucleotide sequence of SEQ ID NO: 2; a super core promoter consisting of the nucleotide sequence of SEQ ID NO: 5; a protein coding sequence consisting of the nucleotide sequence of SEQ ID NO: 49; optionally, a Woodchuck Hepatitis Virus Post- transcriptional Regulatory Element (WPRE) consisting of the nucleotide sequence of SEQ ID NO: 50; optionally, a polyadenylation sequence consisting of the nucleotide sequence of SEQ ID NO: 51; and a 3’ ITR.

75. The polynucleotide according to any of claims 72 to 74, wherein the polynucleotide comprises a nucleotide sequence which is at least 90% identical to SEQ ID NO:

58.

76. 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 CFI; optionally, a Woodchuck Hepatitis Virus Post-transcriptional Regulatory Element (WPRE); optionally, a polyadenylation sequence; and a 3’ ITR.

77. The polynucleotide according to claim 76, 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: 2; a regulatory element consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 15; a CFI coding sequence consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 33; 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: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 51; and a 3’ ITR.

78. The polynucleotide according to claim 76 or 77, comprising: a 5’ ITR; a kidney-specific promoter consisting of the nucleotide sequence of SEQ ID NO: 2; a regulatory element consisting of the nucleotide sequence of SEQ ID NO: 15; a protein coding sequence consisting of the nucleotide sequence of SEQ ID NO: 33; optionally, a Woodchuck Hepatitis Virus Post- transcriptional Regulatory Element (WPRE) consisting of the nucleotide sequence of SEQ ID NO: 50; optionally, a polyadenylation sequence consisting of the nucleotide sequence of SEQ ID NO: 51; and a 3’ ITR.

79. The polynucleotide according to any of claims 76 to 78, wherein the polynucleotide comprises a nucleotide sequence which is at least 90% identical to SEQ ID NO: 59 or 84.

80. The polynucleotide according to claim 76, 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: 2; a regulatory element consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 15; a CFI coding sequence consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 34; 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: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 51; and a 3’ ITR.

81. The polynucleotide according to claim 76 or 80, comprising: a 5’ ITR; a kidney-specific promoter consisting of the nucleotide sequence of SEQ ID NO: 2; a regulatory element consisting of the nucleotide sequence of SEQ ID NO: 15; a protein coding sequence consisting of the nucleotide sequence of SEQ ID NO: 34; optionally, a Woodchuck Hepatitis Virus Post- transcriptional Regulatory Element (WPRE) consisting of the nucleotide sequence of SEQ ID NO: 50; optionally, a polyadenylation sequence consisting of the nucleotide sequence of SEQ ID NO: 51; and a 3’ ITR.

82. The polynucleotide according to any of claims 76, 80 or 81, wherein the polynucleotide comprises a nucleotide sequence which is at least 90% identical to SEQ ID NO:

60.

83. The polynucleotide according to claim 76, 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: 2; a regulatory element consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 15; a CFI coding sequence consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 35; 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: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 51; and a 3’ ITR.

84. The polynucleotide according to claim 76 or 83, comprising: a 5’ ITR; a kidney-specific promoter consisting of the nucleotide sequence of SEQ ID NO: 2; a regulatory element consisting of the nucleotide sequence of SEQ ID NO: 15; a protein coding sequence consisting of the nucleotide sequence of SEQ ID NO: 35; optionally, a Woodchuck Hepatitis Virus Post- transcriptional Regulatory Element (WPRE) consisting of the nucleotide sequence of SEQ ID NO: 50; optionally, a polyadenylation sequence consisting of the nucleotide sequence of SEQ ID NO: 51; and a 3’ ITR.

85. The polynucleotide according to any of claims 76, 83 or 84, wherein the polynucleotide comprises a nucleotide sequence which is at least 90% identical to SEQ ID NO:

61.

86. 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 CFH; optionally, a Woodchuck Hepatitis Virus Post-transcriptional Regulatory Element (WPRE); optionally, a polyadenylation sequence; and a 3’ ITR.

87. The polynucleotide according to claim 86, 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: 2; a regulatory element consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 15; a CFH coding sequence consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 37; 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: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 51; and a 3’ ITR.

88. The polynucleotide according to claim 86 or 87, comprising: a 5’ ITR; a kidney-specific promoter consisting of the nucleotide sequence of SEQ ID NO: 2; a regulatory element consisting of the nucleotide sequence of SEQ ID NO: 15; a CFH coding sequence consisting of the nucleotide sequence of SEQ ID NO: 37; optionally, a Woodchuck Hepatitis Virus Post- transcriptional Regulatory Element (WPRE) consisting of the nucleotide sequence of SEQ ID NO: 50; optionally, a polyadenylation sequence consisting of the nucleotide sequence of SEQ ID NO: 51; and a 3’ ITR.

89. The polynucleotide according to any of claims 86 to 88, wherein the polynucleotide comprises a nucleotide sequence which is at least 90% identical to SEQ ID NO:

62.

90. 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 FHL- 1; optionally, a Woodchuck Hepatitis Virus Post-transcriptional Regulatory Element (WPRE); optionally, a polyadenylation sequence; and a 3’ ITR.

91. The polynucleotide according to claim 90, 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: 2; a regulatory element consisting of a nucleotide sequence having atleast 80% sequence identity to SEQ ID NO: 15; a FHL-1 coding sequence consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 39; 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: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 51; and a 3’ ITR.

92. The polynucleotide according to claim 90 or 91, comprising: a 5’ ITR; a kidney-specific promoter consisting of the nucleotide sequence of SEQ ID NO: 2; a regulatory element consisting of the nucleotide sequence of SEQ ID NO: 15; a FHL-1 coding sequence consisting of the nucleotide sequence of SEQ ID NO: 39; optionally, a Woodchuck Hepatitis Virus Post- transcriptional Regulatory Element (WPRE) consisting of the nucleotide sequence of SEQ ID NO: 50; optionally, a polyadenylation sequence consisting of the nucleotide sequence of SEQ ID NO: 51; and a 3’ ITR.

93. The polynucleotide according to any of claims 90 to 92, wherein the polynucleotide comprises a nucleotide sequence which is at least 90% identical to SEQ ID NO:

63.

94. 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 CFI and FHL-1; optionally, a Woodchuck Hepatitis Virus Post-transcriptional Regulatory Element (WPRE); optionally, a polyadenylation sequence; and a 3’ ITR.

95. The polynucleotide according to claim 94, wherein the protein coding sequence encodes from 5’ to 3’: CFI; a 2A self-cleaving peptide; and FHL-1.

96. The polynucleotide according to claim 95, 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: 2; a regulatory element consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 15; a protein coding sequence consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 47; 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: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 51; and a 3’ ITR.

97. The polynucleotide according to claim 95 or 96, comprising: a 5’ ITR; a kidney-specific promoter consisting of the nucleotide sequence of SEQ ID NO: 2; a regulatory elementconsisting of the nucleotide sequence of SEQ ID NO: 15; a protein coding sequence consisting of the nucleotide sequence of SEQ ID NO: 47; optionally, a Woodchuck Hepatitis Virus Post- transcriptional Regulatory Element (WPRE) consisting of the nucleotide sequence of SEQ ID NO: 50; optionally, a polyadenylation sequence consisting of the nucleotide sequence of SEQ ID NO: 51; and a 3’ ITR.

98. The polynucleotide according to any of claims 95 to 97, wherein the polynucleotide comprises a nucleotide sequence which is at least 90% identical to SEQ ID NO:

64.

99. The polynucleotide according to claim 94, wherein the protein coding sequence encodes from 5’ to 3’: FHL-1; a 2A self-cleaving peptide; and CFI.

100. The polynucleotide according to claim 99, 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: 2; a regulatory element consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 15; a protein coding sequence consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 49; 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: 50; optionally, a polyadenylation sequence consisting of a nucleotide sequence having at least 80% sequence identity to SEQ ID NO: 51; and a 3’ ITR.

101. The polynucleotide according to claim 99 or 100, comprising: a 5’ ITR; a kidney-specific promoter consisting of the nucleotide sequence of SEQ ID NO: 2; a regulatory element consisting of the nucleotide sequence of SEQ ID NO: 15; a protein coding sequence consisting of the nucleotide sequence of SEQ ID NO: 49; optionally, a Woodchuck Hepatitis Virus Post- transcriptional Regulatory Element (WPRE) consisting of the nucleotide sequence of SEQ ID NO: 50; optionally, a polyadenylation sequence consisting of the nucleotide sequence of SEQ ID NO: 51; and a 3’ ITR.

102. The polynucleotide according to any of claims 99 to 101, wherein the polynucleotide comprises a nucleotide sequence which is at least 90% identical to SEQ ID NO:

65.

103. An AAV vector comprising the polynucleotide according to any of claims 1 to 102.

104. An AAV vector particle comprising the polynucleotide according to any of claims 1 to 102.

105. The AAV vector particle according to claim 104, wherein the AAV vector particle is encapsidated by LK03, AAV3B, AAV9, ShH10, AAV-DJ, AAV2, AAV6.2, or AAV5 capsid proteins.

106. The AAV vector particle according to claim 104 or 105, wherein the AAV vector particle is encapsidated by LK03 capsid proteins.

107. The AAV vector particle according to any of claims 104 to 106, 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:

67.

108. The AAV vector particle according to any of claims 104 to 107, wherein the AAV vector particle is encapsidated by capsid proteins consisting of the amino acid sequence of SEQ ID NO:

67.

109. A pharmaceutical composition comprising the polynucleotide according to any of claims 1 to 102, the AAV vector according to claim 103, or the AAV vector particle according to any of claims 104 to 108, and a pharmaceutically acceptable carrier, diluent and / or excipient.

110. A polynucleotide according to any of claims 1 to 102, an AAV vector according to claim 103, an AAV vector particle according to any of claims 104 to 108, or a pharmaceutical composition according to claim 109, for use as a medicament.

111. Use of a polynucleotide according to any of claims 1 to 102, an AAV vector according to claim 103, an AAV vector particle according to any of claims 104 to 108, or a pharmaceutical composition according to claim 109, for the manufacture of a medicament.

112. A polynucleotide according to any of claims 1 to 102, an AAV vector according to claim 103, an AAV vector particle according to any of claims 104 to 108, or a pharmaceutical composition according to claim 109, for use in treating or preventing a complement-mediated kidney disease.

113. Use of a polynucleotide according to any of claims 1 to 102, an AAV vector according to claim 103, an AAV vector particle according to any of claims 104 to 108, or a pharmaceutical composition according to claim 109, for the manufacture of a medicament for treating or preventing a complement-mediated kidney disease.

114. A method of treating or preventing a complement-mediated kidney disease, the method comprising administering a polynucleotide according to any of claims 1 to 102, an AAV vector according to claim 103, an AAV vector particle according to any of claims 104 to 108, or a pharmaceutical composition according to claim 109, to a subject in need thereof.

115. The polynucleotide, AAV vector, AAV vector particle, or pharmaceutical composition for use according to claim 112, the use according to claim 113, or the method according to claim114, wherein the complement-mediated kidney disease is IgA nephropathy, membranous nephropathy, or C3 glomerulopathy.

116. The polynucleotide, AAV vector, AAV vector particle, or pharmaceutical composition for use according to claim 112, the use according to claim 113, or the method according to claim 114, wherein the complement-mediated kidney disease is IgA nephropathy.

117. The polynucleotide, AAV vector, AAV vector particle, or pharmaceutical composition for use according to any of claims 112 or 115-116, the use according to any of claims claim 113 or 115-116, or the method according to any of claims 114-116, wherein the polynucleotide, 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, preferably wherein the polynucleotide, AAV vector, AAV vector particle, or pharmaceutical composition is administered by renal artery injection.

118. The polynucleotide, AAV vector, AAV vector particle, or pharmaceutical composition for use according to any of claims 112 or 115-117, the use according to any of claims claim 113 or 115-117, or the method according to any of claims 114-117, wherein the AAV vector, AAV vector particle, or pharmaceutical composition is administered in a dose of from about 1x106vg / kg to about 1x1014vg / kg.

119. A vector comprising the polynucleotide according to any of claims 1 to 102.

120. The vector according to claim 119, wherein the vector is a plasmid.

121. A kit for production of AAV vector particles comprising, a vector according to claim 119 or 120, and one or more helper plasmids encoding AAV replication and capsid proteins 122. An isolated cell comprising the polynucleotide according to any of claims 1 to 102, the AAV vector according to claim 103, the AAV vector particle according to any of claims 104 to 108, or the vector according to claim 119 or 120.

123. The cell according to claim 122, wherein the cell is a packaging cell.

Images