Genomic disorders resulting from large rearrangements of the genome remain an important unsolved issue in gene therapy. Chromosome transplantation, defined as the perfect replacement of an endogenous chromosome with a homologous one, has the potential of curing this kind of disorders. Here we report the first successful case of chromosome transplantation by replacement of an endogenous X chromosome carrying a mutation in the Hprt gene with a normal one in mouse embryonic stem cells (ESCs), correcting the genetic defect. The defect was also corrected by replacing the Y chromosome with an X chromosome. Chromosome transplanted clones maintained in vitro and in vivo features of stemness and contributed to chimera formation. Genome integrity was confirmed by cytogenetic and molecular genome analysis. The approach here proposed, with some modifications, might be used to cure various disorders due to other X chromosome aberrations in induced pluripotent stem (iPS) cells derived from affected patients.

Chromosome transplantation as a novel approach for correcting complex genomic disorders / M. Paulis, A. Castelli, L. Susani, M. Lizier, I. Lagutina, M.L. Focarelli, C. Recordati, P. Uva, F. Faggioli, T. Neri, E. Scanziani, C. Galli, F. Lucchini, A. Villa, P. Vezzoni. - In: ONCOTARGET. - ISSN 1949-2553. - 6:34(2015), pp. 35218-35230. [10.18632/oncotarget.6143]

Chromosome transplantation as a novel approach for correcting complex genomic disorders

M.L. Focarelli;C. Recordati;F. Faggioli;E. Scanziani;
2015

Abstract

Genomic disorders resulting from large rearrangements of the genome remain an important unsolved issue in gene therapy. Chromosome transplantation, defined as the perfect replacement of an endogenous chromosome with a homologous one, has the potential of curing this kind of disorders. Here we report the first successful case of chromosome transplantation by replacement of an endogenous X chromosome carrying a mutation in the Hprt gene with a normal one in mouse embryonic stem cells (ESCs), correcting the genetic defect. The defect was also corrected by replacing the Y chromosome with an X chromosome. Chromosome transplanted clones maintained in vitro and in vivo features of stemness and contributed to chimera formation. Genome integrity was confirmed by cytogenetic and molecular genome analysis. The approach here proposed, with some modifications, might be used to cure various disorders due to other X chromosome aberrations in induced pluripotent stem (iPS) cells derived from affected patients.
Cell therapy; Chromosome transplantation; Embryonic stem cells; Genomic disorders; Microcell fusion; Animals; Embryonic Stem Cells; Genetic Diseases, Inborn; Genetic Therapy; Hypoxanthine Phosphoribosyltransferase; Male; Mice; Mice, Knockout; Mice, Nude; Mutation; X Chromosome; Oncology
Settore VET/03 - Patologia Generale e Anatomia Patologica Veterinaria
2015
http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=download&path%5B%5D=6143&path%5B%5D=15301
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/503516
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