Plasmid vectors and nanoparticles for treating ocular disorders

2:

• The plasmid vector of claim 1, wherein the GRK1 promoter is upstream of the heterologous gene and the S/MAR enhancer is downstream of the heterologous gene.

3:

• The plasmid vector of claim 1, further including a human beta-globin polyadenosine (polyA) signal sequence.

4:

• The plasmid vector of claim 1, wherein the beta-globin polyA signal sequence is downstream of the heterologous gene and upstream of the S/MAR enhancer.

5:

• The plasmid vector of claim 1, wherein the retinal disorder is an inheritable retinal disorder caused by a mutation of a gene encoding an ocular protein.

6:

• The plasmid vector of claim 1, wherein the inheritable retinal disorder is selected from Stargardt Disease, Leber's congenital amaurosis (LCA), pseudoxanthoma elasticum, rod cone dystrophy, exudative vitreoretinopathy, Joubert Syndrome, CSNB-1 C, retinitis pigmentosa, stickler syndrome, microcephaly, choriorretinopathy, CSNB 2, Usher syndrome, Wagner syndrome, or age-related macular degeneration.

7:

• The plasmid vector of claim 1, wherein the heterologous gene is selected from Retinal pigment epithelium-specific 65 kDa protein (RPE 65), vascular endothelial growth factor (VEGF) inhibitor or soluble VEGF receptor 1 (sFif1), (Rab escort protein-1) REP1, L-opsin, rhodopsin (Rho), phosphodiesterase 6(3 (PDE613), ATP-binding cassette, sub-family A, member 4 (ABCA4), lecithin retinol acyltransferase (LRAT), Retinal degeneration, slow/Peripherin (RDS/Peripherin), Tyrosine-protein kinase Mer (MERTK), Inosine-5 prime-monophosphate dehydrogenase, type I (IMPDHI), guanylate cyclase 2D (GUCY2D), aryl-hydrocarbon interacting protein-like 1 (AIPL 1), retinitis pigmentosa GTPase regulator interacting protein 1 (RPGRIPI), Inosine-5-prime-monophosphate dehydrogenase, type I (IMPDH1 guanine nucleotide binding protein, alpha transducing activity polypeptide 2 (GNAT2), cyclic nucleotide gated channel beta 3 (CNGB3), retinoschisin 1 (Rs1), ocular albinism type 1 (OA1), oculocutaneous albinism type 1 (OCA1) tyrosinase, P21 WAF-1/Cip1, platelet-derived growth factor (PDGF), Endostatin Angiostatin, arylsulfatase B, 13-glucuronidase, usherin 2A (USH2A), CEP290, ABCC, RIMS1, LRP5, CC2D2A, TRPM1, IFT-172, COL11A1, TUBGCP6, KIAA1549, CACNA1F, MYO7A, VCAN, or HMCN1.

8:

• The plasmid vector of claim 1, wherein the retinal disorder is Stargardt Disease.

9:

• The plasmid vector of claim 8, wherein the heterologous gene is ABCA4.

10:

• The plasmid vector of claim 1, having the nucleic acid sequence of SEQ ID NO:
• 1.

11:

• A self-assembled nanoparticle comprising a plurality of pH sensitive multifunctional cationic lipids complexed with one or more plasmid vector(s) of claim 1.

12:

• The self-assembled nanoparticle of claim 11, wherein the pH sensitive multifunctional cationic lipids comprise pH sensitive multifunctional amino lipids.

13:

• The self-assembled nanoparticle of claim 12, having an amine to phosphate (N/P) ratio of about 4 to about 12.

14:

• The self-assembled nanoparticle of claim 11, wherein the pH sensitive multifunctional cationic lipids further include at least one targeting group that targets and/or binds to a retinal or visual protein.

15:

• The self-assembled nanoparticles of claim 14, wherein the at least one targeting group includes a retinoid or retinoid derivative that targets and/or binds to an interphotoreceptor retinoid binding protein.

16:

• The self-assembled nanoparticles of claim 14, wherein the at least one targeting group includes all-trans-retinylamine or (1R)-3-amino-1-[3-(cyclohexylmethoxy)phenyl]propan-1-ol.

17:

• The self-assembled nanoparticles of claim 14, wherein the pH sensitive multifunctional cationic lipids include a cysteine residue and the at least one targeting group is covalently attached to a thiol group of the cysteine residue by a linker.

18:

• The self-assembled nanoparticles of claim 17, wherein the linker comprises a polyamino acid group, a polyalkylene group, or a polyethylene glycol group.

19:

• The self-assembled nanoparticles of claim 18, wherein the linker comprises an acid labile bond.

20:

• The self-assembled nanoparticles of claim 14, further being PEGylated.

21:

• The self-assembled nanoparticles of claim 14, wherein the pH sensitive multifunctional cationic lipids comprise (1-aminoethyl)iminobis[N-(oleoylcysteinyl-1-amino-ethyl)propionamide) (ECO) or an analogue or derivative thereof.

22-35. (canceled)

36:

• A pharmaceutical composition comprising an aqueous solution of the self-assembled nanoparticles of claim 11.

37-59. (canceled)