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Polyclonal long-term MFGS-gp91phox marking in rhesus macaques after nonmyeloablative transplantation with transduced autologous peripheral blood progenitor cells.

Publication ,  Journal Article
Brenner, S; Ryser, MF; Choi, U; Whiting-Theobald, N; Kuhlisch, E; Linton, G; Kang, E; Lehmann, R; Rosen-Wolff, A; Rudikoff, AG; Farese, AM ...
Published in: Mol Ther
August 2006

We have recently reported that the RD114-pseudotyped MFGS-gp91phox vector achieves unprecedented levels of correction of the NADPH-oxidase gp91phox (approved gene symbol CYBB) defect in CD34(+) cells from patients with X-linked chronic granulomatous disease in the NOD/SCID mouse model. Considering clinical use of this vector, we transplanted autologous mobilized peripheral blood CD34(+) progenitor cells, transduced with the RD114-MFGS-gp91phox vector, into two healthy rhesus macaques following nonmyeloablative conditioning. The moderately high levels of in vivo marking seen in the first months following transduction decreased and stabilized at about 8 months posttransplant. Marking for both healthy animals after 15 months was 0.3 to 1.3 vector copies per 100 cells in lymphocytes, neutrophils, and monocytes. Vector insertion analyses performed by linear amplification-mediated PCR and sequencing identified 32 and 45 separate insertion sites in the animals. Identical insertion sites were found in myeloid cells and lymphocytes, demonstrating the successful transduction of lymphomyeloid progenitors. Some inserts landed in the vicinity of genes controlling cell cycle and proliferation. Statistical analyses of insertion sites 1 year posttransplant suggest a high diversity of insertion sites despite low marking.

Duke Scholars

Published In

Mol Ther

DOI

ISSN

1525-0016

Publication Date

August 2006

Volume

14

Issue

2

Start / End Page

202 / 211

Location

United States

Related Subject Headings

  • Whole-Body Irradiation
  • Virus Integration
  • Transplantation, Autologous
  • Transplantation Conditioning
  • Transgenes
  • Transduction, Genetic
  • NADPH Oxidases
  • NADPH Oxidase 2
  • Membrane Glycoproteins
  • Male
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Brenner, S., Ryser, M. F., Choi, U., Whiting-Theobald, N., Kuhlisch, E., Linton, G., … Malech, H. L. (2006). Polyclonal long-term MFGS-gp91phox marking in rhesus macaques after nonmyeloablative transplantation with transduced autologous peripheral blood progenitor cells. Mol Ther, 14(2), 202–211. https://doi.org/10.1016/j.ymthe.2006.01.015
Brenner, Sebastian, Martin F. Ryser, Uimook Choi, Narda Whiting-Theobald, Eberhard Kuhlisch, Gilda Linton, Elizabeth Kang, et al. “Polyclonal long-term MFGS-gp91phox marking in rhesus macaques after nonmyeloablative transplantation with transduced autologous peripheral blood progenitor cells.Mol Ther 14, no. 2 (August 2006): 202–11. https://doi.org/10.1016/j.ymthe.2006.01.015.
Brenner S, Ryser MF, Choi U, Whiting-Theobald N, Kuhlisch E, Linton G, et al. Polyclonal long-term MFGS-gp91phox marking in rhesus macaques after nonmyeloablative transplantation with transduced autologous peripheral blood progenitor cells. Mol Ther. 2006 Aug;14(2):202–11.
Brenner, Sebastian, et al. “Polyclonal long-term MFGS-gp91phox marking in rhesus macaques after nonmyeloablative transplantation with transduced autologous peripheral blood progenitor cells.Mol Ther, vol. 14, no. 2, Aug. 2006, pp. 202–11. Pubmed, doi:10.1016/j.ymthe.2006.01.015.
Brenner S, Ryser MF, Choi U, Whiting-Theobald N, Kuhlisch E, Linton G, Kang E, Lehmann R, Rosen-Wolff A, Rudikoff AG, Farese AM, Macvittie TJ, Roesler J, Horwitz ME, Malech HL. Polyclonal long-term MFGS-gp91phox marking in rhesus macaques after nonmyeloablative transplantation with transduced autologous peripheral blood progenitor cells. Mol Ther. 2006 Aug;14(2):202–211.
Journal cover image

Published In

Mol Ther

DOI

ISSN

1525-0016

Publication Date

August 2006

Volume

14

Issue

2

Start / End Page

202 / 211

Location

United States

Related Subject Headings

  • Whole-Body Irradiation
  • Virus Integration
  • Transplantation, Autologous
  • Transplantation Conditioning
  • Transgenes
  • Transduction, Genetic
  • NADPH Oxidases
  • NADPH Oxidase 2
  • Membrane Glycoproteins
  • Male