Gene targeting in stem cells from individuals with osteogenesis imperfecta

Science. 2004 Feb 20;303(5661):1198-201. doi: 10.1126/science.1088757.


Adult stem cells offer the potential to treat many diseases through a combination of ex vivo genetic manipulation and autologous transplantation. Mesenchymal stem cells (MSCs, also referred to as marrow stromal cells) are adult stem cells that can be isolated as proliferating, adherent cells from bones. MSCs can differentiate into multiple cell types present in several tissues, including bone, fat, cartilage, and muscle, making them ideal candidates for a variety of cell-based therapies. Here, we have used adeno-associated virus vectors to disrupt dominant-negative mutant COL1A1 collagen genes in MSCs from individuals with the brittle bone disorder osteogenesis imperfecta, demonstrating successful gene targeting in adult human stem cells.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alleles
  • Animals
  • Bone Marrow Cells / physiology
  • Cell Differentiation
  • Cells, Cultured
  • Collagen Type I / chemistry
  • Collagen Type I / genetics*
  • Collagen Type I / metabolism
  • Dependovirus / genetics
  • Gene Targeting*
  • Genetic Therapy
  • Genetic Vectors
  • Humans
  • Kanamycin Kinase / genetics
  • Male
  • Mesenchymal Stem Cells / physiology*
  • Mice
  • Osteogenesis
  • Osteogenesis Imperfecta / genetics*
  • Osteogenesis Imperfecta / therapy*
  • Point Mutation
  • Recombination, Genetic
  • Stem Cell Transplantation


  • Collagen Type I
  • Kanamycin Kinase