Scaffold attachment region-containing retrovirus vectors improve long-term proviral expression after transplantation of GFP-modified CD34+ baboon repopulating cells

Peter Kurre, Julia Morris, Bobbie Thomasson, Donald B. Kohn, Hans Peter Kiem

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Sustained high-level proviral expression is important for clinical applications of gene therapy. Genetic elements including the β-interferon scaffold attachment region (SAR) have been shown to improve transgene expression in hematopoietic cells. We hypothesized that SAR elements might improve expression and allow the preselection of successfully transduced cells. Thus, we transplanted green fluorescent protein (GFP)-selected cells, half of which had been transduced with either SAR or non-SAR-containing retrovirus vectors, into 3 animals. All animals showed delayed engraftment compared with historic controls (28 vs 15.5 days). GFP marking was seen at levels up to 8% but declined over the first 6 weeks. Importantly, fluorescence intensity was 2- to 9-fold increased in progeny of SAR versus non-SAR vector-modified cells in all hematopoietic lineages for the duration of follow-up (6-12 months). In conclusion, the use of SAR-containing vectors improved transgene expression in hematopoietic repopulating cells, which may obviate the need for multicopy integration to achieve high-level expression and reduce the risk for insertional mutagenesis.

Original languageEnglish (US)
Pages (from-to)3117-3119
Number of pages3
JournalBlood
Volume102
Issue number9
DOIs
StatePublished - Nov 1 2003
Externally publishedYes

Fingerprint

Matrix Attachment Regions
Papio
Retroviridae
Green Fluorescent Proteins
Transplantation
Transgenes
Animals
Gene therapy
Mutagenesis
Insertional Mutagenesis
Genetic Therapy
Interferons
Fluorescence

ASJC Scopus subject areas

  • Hematology

Cite this

Scaffold attachment region-containing retrovirus vectors improve long-term proviral expression after transplantation of GFP-modified CD34+ baboon repopulating cells. / Kurre, Peter; Morris, Julia; Thomasson, Bobbie; Kohn, Donald B.; Kiem, Hans Peter.

In: Blood, Vol. 102, No. 9, 01.11.2003, p. 3117-3119.

Research output: Contribution to journalArticle

Kurre, Peter ; Morris, Julia ; Thomasson, Bobbie ; Kohn, Donald B. ; Kiem, Hans Peter. / Scaffold attachment region-containing retrovirus vectors improve long-term proviral expression after transplantation of GFP-modified CD34+ baboon repopulating cells. In: Blood. 2003 ; Vol. 102, No. 9. pp. 3117-3119.
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abstract = "Sustained high-level proviral expression is important for clinical applications of gene therapy. Genetic elements including the β-interferon scaffold attachment region (SAR) have been shown to improve transgene expression in hematopoietic cells. We hypothesized that SAR elements might improve expression and allow the preselection of successfully transduced cells. Thus, we transplanted green fluorescent protein (GFP)-selected cells, half of which had been transduced with either SAR or non-SAR-containing retrovirus vectors, into 3 animals. All animals showed delayed engraftment compared with historic controls (28 vs 15.5 days). GFP marking was seen at levels up to 8{\%} but declined over the first 6 weeks. Importantly, fluorescence intensity was 2- to 9-fold increased in progeny of SAR versus non-SAR vector-modified cells in all hematopoietic lineages for the duration of follow-up (6-12 months). In conclusion, the use of SAR-containing vectors improved transgene expression in hematopoietic repopulating cells, which may obviate the need for multicopy integration to achieve high-level expression and reduce the risk for insertional mutagenesis.",
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AU - Kohn, Donald B.

AU - Kiem, Hans Peter

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