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Comparison of HIV- and EIAV-based vectors on their efficiency in transducing murine and human hematopoietic repopulating cells.
Mol Ther. 2005 Sep; 12(3):537-46.MT

Abstract

The use of lentiviral vectors for gene transfer into hematopoietic stem cells has raised considerable interest as these vectors can permanently integrate their genome into quiescent cells. Vectors based on alternative lentiviruses would theoretically be safer than HIV-1-based vectors and could also be used in HIV-positive patients, minimizing the risk of generating replication-competent virus. Here we report the use of third-generation equine infectious anemia virus (EIAV)- and HIV-1-based vectors with minimal viral sequences and absence of accessory proteins. We have compared their efficiency in transducing mouse and human hematopoietic stem cells both in vitro and in vivo to that of a previously documented second-generation HIV-1 vector. The third-generation EIAV- and HIV-based vectors gave comparable levels of transduction and transgene expression in both mouse and human NOD/SCID repopulating cells but were less efficient than the second-generation HIV-1 vector in human HSCs. For the EIAV vector this is possibly a reflection of the lower protein expression levels achieved in human cells, as vector copy number analysis revealed that this vector exhibited a trend to integrate equally efficiently compared to the third-generation HIV-1 vector in both mouse and human HSCs. Interestingly, the presence or absence of Tat in viral preparations did not influence the transduction efficiency of HIV-1 vectors in human HSCs.

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Authors+Show Affiliations

Siapati EK
Hematopoietic Stem Cell Laboratory, Cancer Research UK, 44 Lincoln's Inn Fields, London WC2A 3PX, UK.
Bigger BW
No affiliation info available
Miskin J
No affiliation info available
Chipchase D
No affiliation info available
Parsley KL
No affiliation info available
Mitrophanous K
No affiliation info available
Themis M
No affiliation info available
Thrasher AJ
No affiliation info available
Bonnet D
No affiliation info available

MeSH

AnimalsAntigens, CD34Cell LineFlow CytometryGene Transfer TechniquesGenetic TherapyGenetic VectorsGreen Fluorescent ProteinsHIVHematopoietic Stem CellsHumansIn Vitro TechniquesInfectious Anemia Virus, EquineLentivirusLeukocyte Common AntigensMiceMice, Inbred C57BLMice, Inbred NODMice, SCIDRNAReverse Transcriptase Polymerase Chain ReactionSpecies SpecificityStem Cells

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

16099415

Citation

Siapati, Elena K., et al. "Comparison of HIV- and EIAV-based Vectors On Their Efficiency in Transducing Murine and Human Hematopoietic Repopulating Cells." Molecular Therapy : the Journal of the American Society of Gene Therapy, vol. 12, no. 3, 2005, pp. 537-46.
Siapati EK, Bigger BW, Miskin J, et al. Comparison of HIV- and EIAV-based vectors on their efficiency in transducing murine and human hematopoietic repopulating cells. Mol Ther. 2005;12(3):537-46.
Siapati, E. K., Bigger, B. W., Miskin, J., Chipchase, D., Parsley, K. L., Mitrophanous, K., Themis, M., Thrasher, A. J., & Bonnet, D. (2005). Comparison of HIV- and EIAV-based vectors on their efficiency in transducing murine and human hematopoietic repopulating cells. Molecular Therapy : the Journal of the American Society of Gene Therapy, 12(3), 537-46.
Siapati EK, et al. Comparison of HIV- and EIAV-based Vectors On Their Efficiency in Transducing Murine and Human Hematopoietic Repopulating Cells. Mol Ther. 2005;12(3):537-46. PubMed PMID: 16099415.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Comparison of HIV- and EIAV-based vectors on their efficiency in transducing murine and human hematopoietic repopulating cells. AU - Siapati,Elena K, AU - Bigger,Brian W, AU - Miskin,James, AU - Chipchase,Daniel, AU - Parsley,Kathryn L, AU - Mitrophanous,Kyriacos, AU - Themis,Mike, AU - Thrasher,Adrian J, AU - Bonnet,Dominique, PY - 2004/08/26/received PY - 2005/01/28/revised PY - 2005/01/28/accepted PY - 2005/8/16/pubmed PY - 2005/12/13/medline PY - 2005/8/16/entrez SP - 537 EP - 46 JF - Molecular therapy : the journal of the American Society of Gene Therapy JO - Mol Ther VL - 12 IS - 3 N2 - The use of lentiviral vectors for gene transfer into hematopoietic stem cells has raised considerable interest as these vectors can permanently integrate their genome into quiescent cells. Vectors based on alternative lentiviruses would theoretically be safer than HIV-1-based vectors and could also be used in HIV-positive patients, minimizing the risk of generating replication-competent virus. Here we report the use of third-generation equine infectious anemia virus (EIAV)- and HIV-1-based vectors with minimal viral sequences and absence of accessory proteins. We have compared their efficiency in transducing mouse and human hematopoietic stem cells both in vitro and in vivo to that of a previously documented second-generation HIV-1 vector. The third-generation EIAV- and HIV-based vectors gave comparable levels of transduction and transgene expression in both mouse and human NOD/SCID repopulating cells but were less efficient than the second-generation HIV-1 vector in human HSCs. For the EIAV vector this is possibly a reflection of the lower protein expression levels achieved in human cells, as vector copy number analysis revealed that this vector exhibited a trend to integrate equally efficiently compared to the third-generation HIV-1 vector in both mouse and human HSCs. Interestingly, the presence or absence of Tat in viral preparations did not influence the transduction efficiency of HIV-1 vectors in human HSCs. SN - 1525-0016 UR - https://www.unboundmedicine.com/medline/citation/16099415/Comparison_of_HIV__and_EIAV_based_vectors_on_their_efficiency_in_transducing_murine_and_human_hematopoietic_repopulating_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1525-0016(05)00108-5 DB - PRIME DP - Unbound Medicine ER -