In Vivo Enrichment of Gene-Modified Cells

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Expression of the inserted therapeutic gene may vanish over time in vivo. Creative Cell's proprietary mutant ABCG2 (mutABCG2) system allows in vivo enrichment of transgenic cells.

Background Information:

• Proprietary ABCG2 selection system >>>

Stem cell-based gene therapy is hindered by the relatively low number and poor survival of ex vivo gene-modified stem cells after their insertion into patients. Even in the case of a reasonable therapeutic effect at the beginning of therapy, often gene silencing occurs, resulting in reduction of transgene positive cells within a few months.

Both the paucity of modified cells and silencing of the transgene can be overcome by the in vivo selection of gene treated cells. The therapeutic transgene is inserted into retrieved stem cells in combination with mutABCG2. Upon re-transplantation into the patient, cells actively expressing both the therapeutic gene and mutABCG2 will enjoy selective survival advantage over unmodified stem cells and modified ones that suppressed transgene expression. Importantly, overexpression of mutABCG2 does not affect haematopoietic cell maturation or induce any immunological reactions in humans.

mutABCG2-mediated enrichment of transgene-carrying hematopoietic stem cells (HSCs) in an animal study. Mice were transplanted with gene-modified HSCs and treated with doxorubicin, a mutABCG2-substrate cytotoxic drug. Unlike GFP-expressing cells, mutABCG2-positive HSCs accumulated in the bone marrow.