Fetal gene therapy of α-thalassemia in a mouse model Academic Article uri icon

Overview

MeSH Major

  • Fetal Therapies
  • Genetic Therapy
  • alpha-Thalassemia

abstract

  • Fetuses with homozygous alpha-thalassemia usually die at the third trimester of pregnancy or soon after birth. Hence, the disease could potentially be a target for fetal gene therapy. We have previously established a mouse model of alpha-thalassemia. These mice mimic the human alpha-thalassemic conditions and can be used as preclinical models for fetal gene therapy. We tested a lentiviral vector containing the HS 2, 3, and 4 of the beta-LCR, a central polypurine tract element, and the beta-globin gene promoter directing either the EGFP or the human alpha-globin gene. We showed that the GFP expression was erythroid-specific and detected in BFU-E colonies and the erythroid progenies of CFU-GEMM. For in utero gene delivery, we did yolk sac vessel injection at midgestation of mouse embryos. The recipient mice were analyzed after birth for human alpha-globin gene expression. In the newborn, human alpha-globin gene expression was detected in the liver, spleen, and peripheral blood. The human alpha-globin gene expression was at the peak at 3-4 months, when it reached 20% in some recipients. However, the expression declined at 7 months. Colony-forming assays in these mice showed low abundance of the transduced human alpha-globin gene in their BFU-E and CFU-GEMM and the lack of its transcript. Thus, lentiviral vectors can be an effective vehicle for delivering the human alpha-globin gene into erythroid cells in utero, but, in the mouse model, delivery at late midgestation could not transduce hematopoietic stem cells adequately to sustain gene expression.

publication date

  • May 22, 2007

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC1885618

Digital Object Identifier (DOI)

  • 10.1073/pnas.0702457104

PubMed ID

  • 17496141

Additional Document Info

start page

  • 9007

end page

  • 11

volume

  • 104

number

  • 21