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High-level transgene expression in human hematopoietic progenitors and differentiated blood lineages after transduction with improved lentiviral vectors.
Blood. 2000 Nov 15; 96(10):3392-8.Blood

Abstract

Recent experiments point to the great value of lentiviral vectors for the transduction of human hematopoietic stem cells (hHSCs). Vectors used so far, however, have been poorly satisfying in terms of either biosafety or efficiency of transgene expression. Herein is described the results obtained with human immunodeficiency virus-based vectors optimized in both of these aspects. It is thus shown that vectors containing the EF1alpha and, to a lesser extent, the phosphoglycerate kinase (PGK) promoter, govern high-level gene expression in human hematopoietic progenitors as well as derived hematopoietic lineages of therapeutic relevance, such as erythrocytes, granulocytes, monocytes, dendritic cells, and megakaryocytes. EF1alpha promoter-containing lentiviral vectors can also induce strong transgene expression in primary T lymphocytes isolated from peripheral blood. A self-inactivating design did not affect the performance of EF1alpha promoter-based vectors but significantly reduced expression from the PGK promoter. This negative effect could nevertheless be largely rescued by inserting the post-transcriptional regulatory element of woodchuck hepatitis virus upstream of the vector 3' long terminal repeat. These results have important practical implications for the genetic treatment of lymphohematologic disorders as well as for the study of hematopoiesis via the lentivector-mediated modification of hHSCs.

Authors+Show Affiliations

Department of Genetics and Microbiology and Division of Hematology, Faculty of Medicine, Geneva, Switzerland.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

11071633

Citation

Salmon, P, et al. "High-level Transgene Expression in Human Hematopoietic Progenitors and Differentiated Blood Lineages After Transduction With Improved Lentiviral Vectors." Blood, vol. 96, no. 10, 2000, pp. 3392-8.
Salmon P, Kindler V, Ducrey O, et al. High-level transgene expression in human hematopoietic progenitors and differentiated blood lineages after transduction with improved lentiviral vectors. Blood. 2000;96(10):3392-8.
Salmon, P., Kindler, V., Ducrey, O., Chapuis, B., Zubler, R. H., & Trono, D. (2000). High-level transgene expression in human hematopoietic progenitors and differentiated blood lineages after transduction with improved lentiviral vectors. Blood, 96(10), 3392-8.
Salmon P, et al. High-level Transgene Expression in Human Hematopoietic Progenitors and Differentiated Blood Lineages After Transduction With Improved Lentiviral Vectors. Blood. 2000 Nov 15;96(10):3392-8. PubMed PMID: 11071633.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - High-level transgene expression in human hematopoietic progenitors and differentiated blood lineages after transduction with improved lentiviral vectors. AU - Salmon,P, AU - Kindler,V, AU - Ducrey,O, AU - Chapuis,B, AU - Zubler,R H, AU - Trono,D, PY - 2000/11/9/pubmed PY - 2001/2/28/medline PY - 2000/11/9/entrez SP - 3392 EP - 8 JF - Blood JO - Blood VL - 96 IS - 10 N2 - Recent experiments point to the great value of lentiviral vectors for the transduction of human hematopoietic stem cells (hHSCs). Vectors used so far, however, have been poorly satisfying in terms of either biosafety or efficiency of transgene expression. Herein is described the results obtained with human immunodeficiency virus-based vectors optimized in both of these aspects. It is thus shown that vectors containing the EF1alpha and, to a lesser extent, the phosphoglycerate kinase (PGK) promoter, govern high-level gene expression in human hematopoietic progenitors as well as derived hematopoietic lineages of therapeutic relevance, such as erythrocytes, granulocytes, monocytes, dendritic cells, and megakaryocytes. EF1alpha promoter-containing lentiviral vectors can also induce strong transgene expression in primary T lymphocytes isolated from peripheral blood. A self-inactivating design did not affect the performance of EF1alpha promoter-based vectors but significantly reduced expression from the PGK promoter. This negative effect could nevertheless be largely rescued by inserting the post-transcriptional regulatory element of woodchuck hepatitis virus upstream of the vector 3' long terminal repeat. These results have important practical implications for the genetic treatment of lymphohematologic disorders as well as for the study of hematopoiesis via the lentivector-mediated modification of hHSCs. SN - 0006-4971 UR - https://www.unboundmedicine.com/medline/citation/11071633/High_level_transgene_expression_in_human_hematopoietic_progenitors_and_differentiated_blood_lineages_after_transduction_with_improved_lentiviral_vectors_ L2 - https://ashpublications.org/blood/article-lookup/doi/&lo.doi; DB - PRIME DP - Unbound Medicine ER -