Chromosome transplantation as a novel approach for correcting complex genomic disorders

Marianna Paulis, Alessandra Castelli, Lucia Susani, Michela Lizier, Irina Lagutina, Maria Luisa Focarelli, Camilla Recordati, Paolo Uva, Francesca Faggioli, Tui Neri, Eugenio Scanziani, Cesare Galli, Franco Lucchini, Anna Villa, Paolo Vezzoni

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)35218-35230
Number of pages13
JournalOncotarget
Volume6
Issue number34
DOIs
Publication statusPublished - 2015

Keywords

  • Cell therapy
  • Chromosome transplantation
  • Embryonic stem cells
  • Genomic disorders
  • Microcell fusion

ASJC Scopus subject areas

  • Oncology

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