Pseudotyped recombinant adeno-associated viral vectors mediate efficient gene transfer into primary human CD34+ peripheral blood progenitor cells

Abstract Background and aims Because of their pluripotency, human CD34+ peripheral blood progenitor cells (PBPC) are targets of interest for the treatment of many acquired and inherited disorders using gene therapeutic approaches. Unfortunately, most current vector systems lack either sufficient tra...

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Bibliographic Details
Published in:Cytotherapy (Oxford, England) England), 2010-01, Vol.12 (1), p.107-112
Main Authors: Veldwijk, Marlon R, Sellner, Leopold, Stiefelhagen, Marius, Kleinschmidt, Jürgen A, Laufs, Stephanie, Topaly, Julian, Fruehauf, Stefan, Zeller, W. Jens, Wenz, Frederik
Format: Article
Language:English
Subjects:
adeno-associated virus
Adult
Advanced Basic Science
Antigens, CD34 - analysis
Dependovirus - genetics
Female
gene transfer
Gene Transfer Techniques
Genetic Vectors
Granulocyte-Macrophage Colony-Stimulating Factor - pharmacology
Humans
Male
Middle Aged
Other
peripheral blood progenitor cells
pseudotyped virus
Stem Cells - immunology
Stem Cells - metabolism
Transduction, Genetic - methods
Transgenes
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Summary:Abstract Background and aims Because of their pluripotency, human CD34+ peripheral blood progenitor cells (PBPC) are targets of interest for the treatment of many acquired and inherited disorders using gene therapeutic approaches. Unfortunately, most current vector systems lack either sufficient transduction efficiency or an appropriate safety profile. Standard single-stranded recombinant adeno-associated virus 2 (AAV2)-based vectors offer an advantageous safety profile, yet lack the required efficiency in human PBPC. Methods A panel of pseudotyped AAV vectors (designated AAV2/x, containing the vector genome of serotype 2 and capsid of serotype x, AAV2/1–AAV2/6) was screened on primary human granulocyte–colony-stimulating factor (G-CSF)-mobilized CD34+ PBPC to determine their gene transfer efficacy. Additionally, double-stranded self-complementary AAV (dsAAV) were used to determine possible second-strand synthesis limitations. Results AAV2/6 vectors proved to be the most efficient [12.8% (1.8–25.4%) transgene-expressing PBPC after a single transduction], being significantly more efficient (all P < 0.005) than the other vectors [AAV2/2, 2.0% (0.2–7.3%); AAV2/1, 1.3% (0.1–2.9%); others,
ISSN:1465-3249
1477-2566
DOI:10.3109/14653240903348293