Abstract
At the gene therapy session of the ICCXV Chromosome Conference (2004), recent advances in the construction of engineered chromosomes and de novo human artificial chromosomes were presented. The long-term aims of these studies are to develop vectors as tools for studying genome and chromosome function and for delivering genes into cells for therapeutic applications. There are two primary advantages of chromosome-based vector systems over most conventional vectors for gene delivery. First, the transferred DNA can be stably maintained without the risks associated with insertion, and second, large DNA segments encompassing genes and their regulatory elements can be introduced, leading to more reliable transgene expression. There is clearly a need for safe and effective gene transfer vectors to correct genetic defects. Among the topics discussed at the gene therapy session and the main focus of this review are requirements for de novo human artificial chromosome formation, assembly of chromatin on de novo human artificial chromosomes, advances in vector construction, and chromosome transfer to cells and animals.
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Acknowledgements
We thank Christine Farr for providing the image of the human X minichromosome, Mitsuo Oshimura and Motonobu Katoh for providing the image of the human 21 minichromosome and for sharing unpublished data, Daniela Moralli for assistance in preparation of the figures and comments on the manuscript, Roger Slee for helpful suggestions and the participants of the ICCXV International Chromosome Conference for stimulating discussions. We apologize for being unable to cite all relevant primary papers due to space limitations. Research in the lab of BRG is funded by INGEN, Indiana University School of Medicine (IUSM) Cytogenetics Division, and an IUSM Pilot Funding Grant. The Indiana Genomics Initiative (INGEN) of Indiana University is supported in part by Lilly Endowment, Inc. Research in Z.L.M.'s group was supported in part by the Wellcome Trust and the Dystrophic Epidermolysis Bullosa Research Association, UK.
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Grimes, B.R., Monaco, Z.L. Artificial and engineered chromosomes: developments and prospects for gene therapy. Chromosoma 114, 230–241 (2005). https://doi.org/10.1007/s00412-005-0017-5
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DOI: https://doi.org/10.1007/s00412-005-0017-5