THERAPY

Abstract

The application provides gene therapies for treating monogenic forms of nephrotic syndrome.

Claims

1. An adeno-associated virus (AAV) vector comprising: a nephrotic syndrome-associated transgene; and minimal nephrin promoter NPHS1 or podocin promoter NPHS2, wherein the nephrotic syndrome-associated transgene is selected from one or more of NPHS1, TRPC6, NUP107, NUP133, NUP160, ACTN4, INF2, ANKFY1, ANLN, CRB2, ITGA3, KANK1, KANK4, MAGI2, MYO1E, OCRL, PTPRO, SMARCAL1, SYNPO, TBC1D8B, XPO5, TNS2 or NLRP3.

2. The AAV vector according to claim 1, wherein the AAV vector is AAV serotype 9, LK03 or 3B.

3. The AAV vector according to claim 1, wherein the AAV vector additionally comprises a Woodchuck hepatitis post-transcriptional regulatory element (WPRE).

4. The AAV vector according to claim 1, wherein the NS-associated transgene is human and/or comprises a hemagglutinin (HA) tag.

5. The AAV vector according to claim 1, wherein the AAV vector additionally comprises a Kozak sequence between the promoter and the NS-associated transgene.

6. The AAV vector according to claim 1, wherein the AAV vector additionally comprises a polyadenylation signal such as bovine growth hormone (bGH) polyadenylation signal.

7-13. (canceled)

14. A method of treating a monogenic form of nephrotic syndrome comprising administering an AAV vector according to claim 1 to a patient with the monogenic form of nephrotic syndrome.

15. The method according to claim 14, wherein the monogenic form of nephrotic syndrome is a monogenic form of steroid-resistant nephrotic syndrome.

16. The method according to claim 14, wherein the patient is human.

17. The method according to claim 16, wherein the patient is a paediatric patient.

18. The method according to claim 14, wherein the AAV vector is administered systemically.

19. The method according to claim 14, wherein the AAV vector is administered by intravenous injection.

20. The method according to claim 14, wherein the AAV vector is administered by injection into the renal artery.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0033] The invention will now be described in detail, by way of example only, with reference to the figures.

[0034] FIG. 1 shows an example DNA sequence for the minimal human nephrin promoter (NPHS1).

[0035] FIG. 2 shows an example DNA sequence for a WPRE sequence.

[0036] FIG. 3 shows an example DNA sequence for a bGH poly(A) signal sequence.

[0037] FIGS. 4A and B show example cDNA sequences for human NPHS1 transgenes.

EXAMPLES

[0038] A suitable AAV serotype will be used to transfect mouse and human podocytes in vitro, and mouse NS knockout models in vivo. The AAV plasmid will have a NPHS1 minimal promoter cassette, WPRE and bGH cassettes, and an SRNS cDNA sequence (i.e., a NS-associated transgene) cloned in.

REFERENCES

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