TY - JOUR
T1 - Chromosome transplantation as a novel approach for correcting complex genomic disorders
AU - Paulis, Marianna
AU - Castelli, Alessandra
AU - Susani, Lucia
AU - Lizier, Michela
AU - Lagutina, Irina
AU - Focarelli, Maria Luisa
AU - Recordati, Camilla
AU - Uva, Paolo
AU - Faggioli, Francesca
AU - Neri, Tui
AU - Scanziani, Eugenio
AU - Galli, Cesare
AU - Lucchini, Franco
AU - Villa, Anna
AU - Vezzoni, Paolo
PY - 2015
Y1 - 2015
N2 - 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 genewith 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.
AB - 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 genewith 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.
KW - cell therapy
KW - chromosome transplantation
KW - embryonic stem cells
KW - genomic disorders
KW - microcell fusion
KW - cell therapy
KW - chromosome transplantation
KW - embryonic stem cells
KW - genomic disorders
KW - microcell fusion
UR - http://hdl.handle.net/10807/69791
UR - http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=download&path%5b%5d=6143&path%5b%5d=15301
U2 - 10.18632/oncotarget.6143
DO - 10.18632/oncotarget.6143
M3 - Article
SN - 1949-2553
VL - 6
SP - 35218
EP - 35230
JO - Oncotarget
JF - Oncotarget
ER -