Download Marrow Protection: Transduction of Hematopoietic Cells with by Joseph R. Bertino PDF

By Joseph R. Bertino

Profitable move of drug resistance genes into hematopoietic stem cells offers promise as a way of shielding sufferers from the myelotoxicity of anti-cancer medicines and will allow dose intensification and higher results. using peripheral blood mobilized progenitor cells has greater the entry to this telephone inhabitants and ex vivo gene move ways. move of drug resistance genes into peripheral blood mobilized progenitor cells including nonselectable genes, additionally deals the opportunity of expression of proteins produced through those genes and correction of genetic deficiencies or expression of different fascinating proteins resembling antibodies. The reports released during this booklet overview the development during this box, emphasizing the paintings performed with retroviral vectors and numerous genes which may be used to confer particular kinds of drug resistance to recipients.

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Read Online or Download Marrow Protection: Transduction of Hematopoietic Cells with Drug Resistance Genes (Progress in Experimental Tumor Research, Vol. 36) PDF

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Extra resources for Marrow Protection: Transduction of Hematopoietic Cells with Drug Resistance Genes (Progress in Experimental Tumor Research, Vol. 36)

Example text

An additional advantage of CD34+ cells from fetal and neonatal sources is that gene expression appears to be more stable in progeny of stem cells from FL and CB than in cells derived from adult tissues. We, and others, have observed silencing of transgenes driven by the Moloney murine leukemia virus (MoMLV) long terminal repeat (LTR) in adult mPB stem cells [32, 33]. In our own investigations, CD34+ cells from FL, CB and mPB, were transduced with a MoMLV-based retroviral vector carrying a mutated nerve growth factor receptor (NGFR).

Regulatory issues would also arise if coculture were used for clinical gene therapy. A conventional supernatant infection protocol was successfully used to transfect long-term repopulating cells in one pediatric clinical trial [34], but not in an adult study [74]. In the pediatric trial, fresh or frozen, thawed virus was added to BM cells for 6 h. i. ranging from 1 to 10 following variable durations of cytokine priming. A single addition of virus, or two additions over 48 h, led to 16–25% CFC transduction [28, 51].

These observations lead to the proposal that fibronectin facilitates retroviral infection of CD34+ cells by co-localizing viral particles with the progenitor cells [135, 136]. Initial studies also suggested that the use of fibronectin in gene transfer protocols overrides the necessity for polycations such as polybrene and protamine. However, a recent report clearly indicates that the inclusion of polycations in addition to fibronectin fragments provides a further increment in transduction of primitive hematopoietic cells [44].

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