Abstract
Mammalian artificial chromosomes (MACs) are non-integrating, autonomously replicating natural chromosome-based vectors that may carry a vast amount of genetic material, which in turn enable potentially prolonged, safe, and regulated therapeutic transgene expression and render MACs as attractive genetic vectors for “gene replacement” or for controlling differentiation pathways in target cells. Satellite-DNA-based artificial chromosomes (SATACs) can be made by induced de novo chromosome formation in cells of different mammalian and plant species. These artificially generated accessory chromosomes are composed of predictable DNA sequences, and they contain defined genetic information. SATACs have already passed a number of obstacles crucial to their further development as gene therapy vectors, including large-scale purification, transfer of purified artificial chromosomes into different cells and embryos, generation of transgenic animals and germline transmission with purified SATACs, and the tissue-specific expression of a therapeutic gene from an artificial chromosome in the milk of transgenic animals. SATACs could be used in cell therapy protocols. For these methods, the most versatile target cell would be one that was pluripotent and self-renewing to address multiple disease target cell types, thus making multilineage stem cells, such as adult derived early progenitor cells and embryonic stem cells, as attractive universal host cells.
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Abbreviations
- ACEs:
-
Artificial chromosome expression system
- CHO:
-
Chinese hamster ovary
- EB:
-
Embryoid body
- EGFP:
-
Enhanced green fluorescent protein
- ESC:
-
Embryonic stem cell
- EPO:
-
Erythropoietin
- FACS:
-
Fluorescence-activated cell sorting
- HAC:
-
Human artificial chromosome
- hESC:
-
Human embryonic stem cell
- HGH:
-
Human growth hormone
- HPRT:
-
Hypoxanthine guanine phosphoribosyl transferase
- HSC:
-
Hematopoietic Stem Cell
- iPS:
-
Induced pluripotent stem
- MAbs:
-
Monoclonal antibodies
- MACs:
-
Mammalian artificial chromosomes
- MMCT:
-
Microcell-mediated chromosome transfer
- MRI:
-
Magnetic resonance imaging
- MSC:
-
Mesenchymal stem cell
- PET:
-
Positron emission tomography
- SATAC:
-
Satellite-DNA-based artificial chromosome
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Acknowledgments
I am greatly indebted to the late Gyula Hadlaczky for the discovery and development of SATACs, and also for facilitating me to work, learn, and progress scientifically under his kind supervision. Our work was supported by a Hungarian National Technology Program Grant: TECH_09_A1-DKMACTER (http://www.nih.gov.hu/english)
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Katona, R.L. De novo formed satellite DNA-based mammalian artificial chromosomes and their possible applications. Chromosome Res 23, 143–157 (2015). https://doi.org/10.1007/s10577-014-9458-0
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DOI: https://doi.org/10.1007/s10577-014-9458-0