Gene therapy
AssigneesFondazione Telethon Ets (50%), Ospedale San Raffaele S.R.L. (50%)
InventorsAlessandro Aiuti, Maria Ester Bernardo, Bernhard Gentner, Stefania Crippa, Serena Scala, Pamela Quaranta
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Abstract
The invention relates to means and methods for gene therapy of lysosomal storage disorders (LSDs), preferably a LSD with skeletal involvement, based on an ex vivo gene therapy approach comprising transduction of autologous hematopoietic stem and progenitor cells (HSPCs) with viral vectors for expressing enzymes that are deficient in the disorders. The final formulation is a suspension of transduced cells in culture medium for the administration to patients affected by the LSDs, preferably preceded by a conditioning regimen.
Claims25
A viral vector comprising an expression cassette for expressing, in a cell, an enzyme that is deficient in a lysosomal storage disorder, preferably in a lysosomal storage disorder with skeletal involvement, said expression cassette comprising:
- a) a promoter and
- b) at least one polynucleotide, operably linked to said promoter, encoding an enzyme that is deficient in a lysosomal storage disorder, wherein said enzyme is selected from the group consisting of:
- alpha-D-mannosidase enzyme, beta-galactosidase enzyme, and N-acetylgalactosamine-6-sulfatase enzyme,
- said viral vector being a lentiviral vector.
The viral vector of claim 13, further comprising one or more of:
- c) a 5′ long terminal repeat (5′ LTR);
- d) an encapsidation signal (Ψ), preferably including the 5′ portion of the gag gene (GA);
- e) a Rev-response element (RRE);
- f) a central polypurine tract (cPPT), g) a central termination sequence (CTS), h) a post-transcriptional regulatory element of woodchuck hepatitis virus (Wpre);
- i) a 3′ long terminal repeat region (3′LTR), preferably self-inactivating (SIN) 3′LTR;
- j) a polyadenylation signal;
- k) an SV40 origin of replication;
- and 1) a bacterial high copy origin of replication (f1 ori).
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Dependencies are inferred from the claim text.