Long-term vector integration site analysis following retroviral mediated gene transfer to hematopoietic stem cells for the treatment of HIV infection

PLoS One. 2009;4(1):e4211. doi: 10.1371/journal.pone.0004211. Epub 2009 Jan 16.

Abstract

We previously reported the efficacy of nonmyeloablative allogeneic transplantation in 2 HIV positive recipients, one of whom received retrovirus transduced hematopoietic stem cells to confer resistance to HIV. Here we report an assessment of retroviral integration sites (RISs) recovered out to 3 years post-transplantation. We identified 213 unique RISs from the patient's peripheral blood samples by linear amplification-mediated PCR (LAM-PCR). While vector integration patterns were similar to that previously reported, only 3.76% of RISs were common among early (up to 3 months) and late samples (beyond 1 year). Additionally, common integration sites were enriched among late samples (14.9% vs. 36.8%, respectively). Three RISs were found near or within known oncogenes, but 2 were limited to early timepoints. Interestingly, an integration site near the MDS1 gene was detected in long-term follow-up samples; however, the overall contribution of MDS1 integrated clone remained stably low during follow-up.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • DNA-Binding Proteins
  • Gene Targeting*
  • Genetic Therapy / methods*
  • Genetic Vectors
  • HIV Infections / therapy*
  • Hematopoietic Stem Cell Transplantation
  • Hematopoietic Stem Cells
  • Humans
  • MDS1 and EVI1 Complex Locus Protein
  • Neoplasm Proteins / genetics
  • Proto-Oncogenes
  • Retroviridae / genetics
  • Transcription Factors
  • Transduction, Genetic
  • Virus Integration*

Substances

  • DNA-Binding Proteins
  • MDS1 and EVI1 Complex Locus Protein
  • MECOM protein, human
  • Neoplasm Proteins
  • Transcription Factors