2005
DOI: 10.1038/sj.gt.3302544
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Silencing p21Waf1/Cip1/Sdi1 expression increases gene transduction efficiency in primitive human hematopoietic cells

Abstract: Adult hematopoietic and other tissue stem cells have highly constrained cell cycling that limits their susceptibility to standard gene therapy vectors, which depend upon chromosomal integration. Using cytokine cocktails to increase transduction efficiency often compromises subsequent stem cell function in vivo. We previously showed that p21Waf1/Cip1/Sdi1 (p21) mediates stem cell quiescence in vivo and decreasing its expression ex vivo leads to an expansion of stem cell pool in vivo. Here, we report that applic… Show more

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Cited by 32 publications
(44 citation statements)
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“…For example, although expression of APOBEC3G in neurons contributes to the restriction of HIV-1, it is present in many cells types and as such, its' expression alone does not explain the high degree of resistance observed in neurons (10,12). The discovery of restriction factors such as TRIMs and APOBECs, whose sole function to date appears to be to inhibit virus replication (28), along with antiviral factors, whose presence or absence within the host cell alters virus replication (14,(32)(33)(34)(35)(36)(37) have highlighted the complexity of mechanisms that govern cellular susceptibility to retroviral infection. Many of these factors are expressed in a wide range of tissues and their expression is increased in response to IFN, suggesting that they function as part of the hosts' antiviral response mechanism (28,29).…”
Section: Resultsmentioning
confidence: 99%
“…For example, although expression of APOBEC3G in neurons contributes to the restriction of HIV-1, it is present in many cells types and as such, its' expression alone does not explain the high degree of resistance observed in neurons (10,12). The discovery of restriction factors such as TRIMs and APOBECs, whose sole function to date appears to be to inhibit virus replication (28), along with antiviral factors, whose presence or absence within the host cell alters virus replication (14,(32)(33)(34)(35)(36)(37) have highlighted the complexity of mechanisms that govern cellular susceptibility to retroviral infection. Many of these factors are expressed in a wide range of tissues and their expression is increased in response to IFN, suggesting that they function as part of the hosts' antiviral response mechanism (28,29).…”
Section: Resultsmentioning
confidence: 99%
“…14 Recently, p21 WAF1/Cip1 gene expression has been reported to affect significantly the expression of transduced genes. 31 Thus, HDAC inhibitors may selectively induce the expression of endogenous genes within certain cell types that regulate the expression of transfected genes. 11 The ability of i.v.…”
Section: Discussionmentioning
confidence: 99%
“…The pseudo-viruses have no difficulty in entering HPCs following the spin infection and they accomplish this more easily than a routine infection with the HIV-1 virus [1][2][3][4][5][6][7]. The HIV-1 Gag in the pseudo-viruses can be easily detected with flow cytometry without a further expression of gag gene from the pseudo-viruses in the cell.…”
Section: Hiv Actively Infects Hpcsmentioning
confidence: 99%
“…As HSCs represent only 0.5-3% of mononuclear cells in human bone marrow, researchers have used CD34 + primary bone marrow cells without a further selection of the CD38 marker nor test of cell function with long-term culture-initiating cell assay (LTC-IC) [1][2][3][4][10][11][12][13]. These CD34 + primary hematopoietic stem and progenitor cells are dubbed HSPC [1][2][3][4][10][11][12][13]. The multipotent progenitor cells, however, are named MPPs, and these cells possess multipotentiality but have a function for limited self-renewal ( Figure 1).…”
Section: Are Hpcs Susceptible To Hiv Infection?mentioning
confidence: 99%
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