Gene therapy vectors for adrenoleukodystrophy and adrenomyeloneuropathy

摘要

The present invention provides compositions comprising retroviral vectors, transduced cells, and methods of using the same for gene therapy. In particular, the present invention relates to lentiviral vectors and cells transduced with those vectors to provide gene therapy to subjects having an adrenoleukodystrophy and/or adrenomyeloneuropathy.

主权项

1. A composition comprising one or more cells that comprise a vector selected from the group consisting of:
a) a vector comprising from 5′ to 3′:
(i) a left (5′) retroviral LTR;(ii) a central polypurine tract/DNA flap (cPPT/FLAP);(iii) a retroviral export element;(iv) a promoter active in a microglial cell, operably linked to a polynucleotide encoding an ATP-binding cassette, sub-family D, member 1 (ABCD1) polypeptide; and(v) a right (3′) retroviral LTR;wherein the vector does not comprise a post-transcriptional regulatory element; b) a lentiviral vector comprising from 5′ to 3′:
(i) a left (5′) LTR;(ii) a cPPT/FLAP;(iii) an RRE;(iv) a MND promoter operably linked to a polynucleotide encoding a human ABCD1 poly peptide;(v) a right (3′) LTR; and(vi) a polyadenylation sequence;wherein the sector does not comprise a post-transcriptional regulatory element; c) a lentiviral vector comprising from 5′ to 3′:
(i) a left (5′) HIV-1 LTR;(ii) a Psi (Ψ) packaging signal;(iii) a cPPT/FLAP;(iv) an RRE;(v) a MND promoter, operably linked to a cDNA encoding a human ABCD1 polypeptide;(vi) a right (3′) self-inactivating (SIN) HIV-1 LTR; and(vii) a rabbit β-globin polyadenylation sequence;wherein the vector does not comprise a post-transcriptional regulatory element; d) a vector comprising from 5′ to 3′:
(i) a left (5′) retroviral LTR;(ii) a central polypurine tract/DNA flap (cPPT/FLAP);(iii) a retroviral export element;(iv) a promoter active in a microglial cell, operably linked to a polynucleotide encoding an ATP-binding cassette, sub-family D, member 1 (ABCD1) polypeptide;(v) a right (3′) retroviral LTR;(vi) a polyadenylation (polyA) sequence; andwherein the vector does not comprise a post-transcriptional regulatory element; and e) a lentiviral vector comprising from 5′ to 3′:
(i) a left (5′) HIV-1 LTR;(ii) a Psi (Ψ) packaging signal;(iii) a cPPT/FLAP;(iv) an RRE;(v) a MND promoter, operably linked to a cDNA encoding a human ABCD1 polypeptide;(vi) a right (3′) self-inactivating (SIN) HIV-1 LTR; and(vii) a polyadenylation (polyA) sequence;wherein the vector does not comprise a post-transcriptional regulatory element.