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

PloS One
Jun HayakawaJohn F Tisdale

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.

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Citations

Dec 20, 2013·Viruses·Michael S Bennett, Ramesh Akkina
Aug 27, 2010·Human Gene Therapy·Ken OhmineDavid W Russell
Aug 9, 2012·Molecular Therapy : the Journal of the American Society of Gene Therapy·Naoya UchidaJohn F Tisdale
Jun 7, 2012·Nature Methods·Leonid V BystrykhGerald de Haan
Sep 28, 2010·Advanced Drug Delivery Reviews·Christopher B DoeringH Trent Spencer
Jan 1, 2014·Molecular Therapy. Methods & Clinical Development·Hans-Peter KiemPunam Malik
Dec 28, 2017·Viruses·Robert J Scarborough, Anne Gatignol
Dec 23, 2020·Human Gene Therapy·Tatjana I CornuToni Cathomen
Apr 4, 2021·Life Sciences·Mohsen SheykhhasanMassoud Saidijam

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Methods Mentioned

BETA
PCR
xenograft

Clinical Trials Mentioned

NCT00005785

Software Mentioned

Real Time Design

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