Gene therapy targeting cord blood-derived CD34+ cells from HIV-exposed infants: preclinical studies
Hematopoietic CD34+ cells from placental and umbilical cord blood (PUCB) can be valuable vehicles for gene therapy of immunodeficiencies and genetic disorders. We have conducted preclinical studies towards the treatment of HIV-1-infected infants with genetically ‘immunized’ CD34+ cells derived from...
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| Hauptverfasser: | , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
07 April 1998
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| In: |
Gene therapy
Year: 1998, Jahrgang: 5, Heft: 2, Pages: 233-239 |
| ISSN: | 1476-5462 |
| DOI: | 10.1038/sj.gt.3300582 |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1038/sj.gt.3300582 Verlag, lizenzpflichtig, Volltext: https://www.nature.com/articles/3300582 
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| Verfasserangaben: | X. Li, A. Gervaix, D. Kang, P. Law, S.A. Spector, A.D. Ho, F. Wong-Staal |
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| 520 | |a Hematopoietic CD34+ cells from placental and umbilical cord blood (PUCB) can be valuable vehicles for gene therapy of immunodeficiencies and genetic disorders. We have conducted preclinical studies towards the treatment of HIV-1-infected infants with genetically ‘immunized’ CD34+ cells derived from PUCB using anti-HIV-1 hairpin ribozyme genes. PUCB was collected from 10 newborns of HIV-1-positive mothers. CD34+ cells were enriched with a modified procedure using Dynal immunomagnetic beads and chymopapain, stimulated with stem cell factor (SCF), IL-3 and IL-6, and transduced using cell-free recombinant retroviral vector (MJT) expressing a ribozyme against the U5 region of HIV-1. No significant differences were observed in the growth pattern of CD34+ cells from normal infants, HIV-1 exposed infants or infants confirmed to be infected by HIV-1. The transduction efficiency of the CD34+ cells from all the infants was also comparable. MJT-transduced CD34+ cells from an HIV-1-infected infant were maintained in a liquid culture system for 4 weeks, and the progeny macrophage cells were challenged with the monocyte-tropic laboratory strain, HIV-Bal, or the HIV-1 isolate from the infant’s mother. Significant inhibition of virus replication was observed in ribozyme-transduced cells. Thus, we have demonstrated efficient and stable gene transfer into progenitor cells from the cord blood of HIV-1-exposed or -infected infants and shown that protection from HIV-1 infection was conferred to the progeny cells produced by CD34+ cells transduced with the anti-HIV ribozyme gene construct. | ||
| 650 | 4 | |a Biomedicine | |
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| 700 | 1 | |a Kang, D. |e VerfasserIn |4 aut | |
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| 700 | 1 | |a Wong-Staal, F. |e VerfasserIn |4 aut | |
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