CD133-targeted gene transfer into long-term repopulating hematopoietic stem cells.
Christian Brendel1, Benjamin Goebel2, Abriss Daniela3
11] Institute for Tumor Biology and Experimental Therapy, Georg-Speyer-Haus, Frankfurt, Germany [2] Current address: Division of Pediatric Hematology/Oncology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Molecular Therapy : the Journal of the American Society of Gene Therapy
|September 6, 2014
Summary
Gene therapy targeting CD133(+) cells with CD133-LV lentiviral vectors enhances gene marking and long-term engraftment of hematopoietic stem cells (HSCs). This method improves gene transfer efficiency for treating blood disorders.
Area of Science:
- Hematology
- Gene Therapy
- Stem Cell Biology
Background:
- Gene therapy for hematological disorders requires efficient genetic modification of hematopoietic stem cells (HSCs).
- CD34(+) cells, a target population, contain a very small fraction of long-term repopulating cells.
- Current lentiviral vectors may not optimally target primitive HSCs for sustained gene therapy.
Purpose of the Study:
- To investigate the efficacy of a novel lentiviral vector (CD133-LV) for gene transfer into primitive human hematopoietic stem cells (HSCs).
- To evaluate the engraftment capability and long-term gene marking of CD133-LV transduced cells compared to a standard vector (VSV-LV).
- To assess the potential of CD133-LV for therapeutic gene delivery in patients with X-linked chronic granulomatous disease.
Main Methods:
- Transduction of unstimulated CD34(+) cells using CD133-LV and VSV-LV.
- In vitro and in vivo (immunodeficient mice) assessment of cell proliferation and engraftment.
- In vivo barcode library transfer to track long-term repopulating capacity and secondary recipient repopulation.
- Application of CD133-LV for therapeutic gene transfer in patient-derived CD34(+) cells.
Main Results:
- CD133-LV preferentially transduced cells with high engraftment potential, showing competitive proliferative advantage.
- CD133-LV-transduced cells exhibited superior repopulating capacity compared to VSV-LV transduced cells.
- Sustained in vivo gene marking was observed with CD133-LV, evidenced by higher barcode recovery and secondary recipient repopulation.
- Successful therapeutic gene transfer into CD34(+) cells from X-linked chronic granulomatous disease patients was demonstrated.
Conclusions:
- Direct gene transfer into CD133(+) cells using CD133-LV facilitates sustained long-term engraftment of gene-corrected cells.
- This targeting strategy offers a promising approach for improving the efficiency of gene therapy for hematological disorders.
- CD133-LV represents a potentially valuable tool for enhancing gene therapy outcomes in stem cell applications.
