Genetically modified somatic cells for sustained secretion of lysosomal proenzymes deficient in lysosomal storage disorders
OwnerMani Ramaswamiinventor
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Abstract
The invention relates to various methods of treating lysosomal storage disorders using somatic cells and methods of delivering therapeutic enzymes. More particularly, gain-of-function or loss-of-function mutations in components of the intracellular Golgi to lysosome sorting pathway are used to enhance secretion of one or more lysosomal enzymes in somatic cells, thereby providing treatment for lysosomal storage disorders, particularly in neuronal cells. In addition, homologous recombination may be used to engineer therapeutically useful cells, for example, somatic cells, such as, glial progenitor cells, mesenchymal stem cells and astrocyte precursor cells, to enhance secretion of one or more lysosomal enzymes.
Claims23
A cell secreting lysosomal proteins, said cell comprising a somatic cell having increased secretion of at least one lysosomal enzyme or proenzyme.
A method of treating the central nervous system in a subject, comprising:
- producing a cell, said cell comprising a glial progenitor cell or an astrocyte precursor cell, having an increased secretion of at least one lysosomal enzyme or proenzyme;
- and
- introducing said cell into the spinal chord or central nervous system of a subject.
A method of treating a mammalian subject thought to be suffering from a lysosomal storage disease, the method comprising:
- culturing one or more cells, wherein the cell is selected from the group consisting of at least one glial progenitor cell, mesenchymal stem cell, and astrocyte precursor cell;
- introducing a nucleic acid sequence of interest into the one or more cells;
- recombining by homologous recombination the nucleic acid sequence of interest and a genomic sequence in the one or more cells, wherein at least a part of the nucleic acid sequence of interest produces an increase in secretion of at least one lysosomal enzyme or proenzyme;
- and
- administering the one or more cells to a mammalian subject.
Dependencies are inferred from the claim text.