Efficient gene transfer into human CD34+ cells by an adenovirus type 35 vector

Sakurai, Fuminori; Mizuguchi, Hiroyuki; Hayakawa, Tetsuo

doi:10.1038/sj.gt.3301959

Cited by 83 publications

(65 citation statements)

References 42 publications

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“…21,50 Ad35 vectors possess several advantages, including low seroprevalence in adults and the capacity to evade immunity for Ad5, although AdF35 vectors are inactivated by anti-Ad5-neutralizing antibodies. [51][52][53] This study indicates that fiber-mutant Ad35 vectors displaying foreign peptides in the fiber knob could be constructed.…”

Section: -F L a G ( H I ) -L 2 A D F 3 -F L A G ( I J ) -L 2 A D F 3 mentioning

confidence: 99%

Development of fiber-substituted adenovirus vectors containing foreign peptides in the adenovirus serotype 35 fiber knob

et al. 2009

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Fiber-substituted adenovirus (Ad) vectors containing fibers of Ad serotype 35 (AdF35) efficiently transduce a variety of human cells because their receptor, human CD46, is ubiquitously expressed on almost all nucleated cells. However, the ubiquitous expression of CD46 might lead to unexpected transduction in untargeted organs. In this study, we developed fiber-modified AdF35 vectors with an integrinbinding Arg-Gly-Asn (RGD) peptide incorporated into the FG, HI or IJ loop, which have been identified as important regions for binding to CD46. Incorporation of foreign peptides into these loops does not inhibit trimerization of the fibers. In CD46-negative cells, fiber-mutant AdF35 vectors containing an RGD peptide in the FG or HI loop showed 6-to 30-fold higher transduction efficiencies in an RGD-peptide-dependent manner than the unmodified AdF35 vectors. In contrast, in CD46-positive cells, insertion of foreign peptides markedly reduced the transduction efficiencies of the AdF35 vectors, indicating that insertion of foreign peptides significantly inhibits binding to CD46. In particular, CD46-mediated transduction was completely diminished by insertion of foreign peptides into the HI loop. Our findings indicate that HI loop is the most suitable domain to mediate a foreign peptide-dependent and CD46-independent transduction by incorporation of foreign peptides into the Ad35 fiber knob.

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Section: -F L a G ( H I ) -L 2 A D F 3 -F L A G ( I J ) -L 2 A D F 3 mentioning

confidence: 99%

Development of fiber-substituted adenovirus vectors containing foreign peptides in the adenovirus serotype 35 fiber knob

et al. 2009

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“…VK10-9 cells can support the replication of Ad35 vectors; however, Ad35 vectors can not grow on 293 cells, as described previously. 10 The final yields of the Ad35 vectors were equivalent to those described previously. 10,23 Relationship between CD46 expression and transduction efficiency in human bone marrow CD34 + cells Recently, the complement regulatory protein CD46 has been identified as a cellular receptor for Ad subgroup B.…”

Section: Construction Of E1/e3-deleted Ad35 Vectors By the Improved Imentioning

confidence: 99%

“…5,9 We have therefore developed a novel Ad vector, Ad35 vector, which is composed of whole Ad35, and have demonstrated that Ad35 vectors achieve higher levels of transduction efficiency without significant toxicity in human bone marrow CD34 + cells than both conventional Ad5 vectors and chimeric Ad5F35 vectors, which are fiber-substituted Ad5 vectors containing Ad35 fiber proteins. 10 Ad35 recognizes CD46 (membrane cofactor protein) as a cellular receptor, 11,12 and CD46 is ubiquitously expressed in almost all human cells except for erythrocytes, 13,14 including human cord blood CD34 + cells. 15 Therefore, human CD34 + cells would be considered to be a suitable target for Ad35 vectors.…”

Section: Introductionmentioning

confidence: 99%

Optimization of adenovirus serotype 35 vectors for efficient transduction in human hematopoietic progenitors: comparison of promoter activities

et al. 2005

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Adenoviral gene transfer to hematopoietic stem cells (HSCs)/ progenitors would provide a new approach to the treatment of hematopoietic diseases and study of the hematopoietic system. We have previously reported that an adenovirus (Ad) vector composed of whole Ad serotype 35 (Ad35), which belongs to subgroup B, shows efficient gene transfer into human bone marrow CD34 + cells. However, Ad35 vector-mediated transduction into human HSCs/progenitors has not yet been fully optimized. In the present study, we have systematically examined promoter activity in the context of Ad35 vectors in human bone marrow CD34 + cells and primitive CD34 + subsets to optimize the transduction efficiency in human hematopoietic stem/progenitor cells. In the first of the transduction experiments, the improved in vitro ligation method was applied to Ad35 vector construction to allow for simple and efficient production of an E1/E3-deleted Ad35 vector. Using this method, we constructed a series of Ad35 vectors encoding the enhanced green fluorescence protein (GFP) under the control of a variety of strong viral and cellular promoters. Of the six types of promoters tested, significantly higher transduction efficiencies were achieved with the human elongation factor 1a promoter (EF1a promoter), the human cytomegalovirus (CMV) immediateearly 1 gene enhancer/b-actin promoter with b-actin intron (CA promoter), and the CMV promoter/enhancer with the largest intron of CMV (intron A) (CMVi promoter) in the human CD34 + cells and the immature subsets (CD34 + CD38 low/À and CD34 + AC133 + subsets). In particular, the CA promoter was found to allow for the highest transduction efficiencies in both the whole human CD34 + cells and the immature hematopoietic subsets. Furthermore, the CA promoter-mediated GFP-expressing cells differentiated into progenitor cells of all lineages. These results indicate the construction of an optimized Ad35 vector backbone for efficient transduction into HSCs/progenitors.

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“…When Ad vectors carry a transgene that exerts cytotoxic effects on transduced cells, Ad vector-mediated hepatic transduction leads to severe hepatotoxicity. [5][6][7] In contrast, human species B Ad serotype 35 (Ad35) vectors, which our group and several others have developed, [8][9][10][11] possess attractive properties that can overcome the drawbacks of conventional Ad5 vectors. First, Ad35 vector-mediated transduction is not hampered by anti-Ad5 antibodies, because Ad35 belongs to a different species (species B) than Ad5 (species C).…”

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confidence: 99%

“…8,12 However, intravenous administration of Ad35 vectors resulted in inefficient transduction in the organs of human CD46-transgenic (CD46TG) mice and cynomolgus monkeys, which express CD46 in a pattern similar to that of humans. [13][14][15] These results indicate that CD46 does not successfully serve as a receptor for intravascularly injected Ad35 vectors and that Ad35 vectors are unsuitable for intravascular transduction.…”

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Adenovirus serotype 35 vector-mediated transduction following direct administration into organs of nonhuman primates

Sakurai

Akitomo

et al. 2008

Gene Ther

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Adenovirus (Ad) serotype 35 (Ad35) vectors have attracted remarkable attention as alternatives to conventional Ad serotype 5 (Ad5) vectors. In a previous study, we showed that intravenously administered Ad35 vectors exhibited a safer profile than Ad5 vectors in cynomolgus monkeys, which ubiquitously express CD46, an Ad35 receptor, in a pattern similar to that in humans. However, the Ad35 vectors poorly transduced the organs. In this study, we examined the transduction properties of Ad35 vectors after local administration into organs of cynomolgus monkeys. The vectors transduced different types of cells depending on the organ. Hepatocytes and microglia were mainly transduced after the vectors were injected into the liver and cerebrum, respectively. Injection of the vectors into the femoral muscle resulted in the transduction of cells that appeared to be fibroblasts and/or macrophages. Conjunctival epithelial cells showed transgene expression following infusion into the vitreous body of the eyeball. Transgene expression was limited to areas around the injection points in most of the organs. In contrast, Ad35 vector-mediated transgene expression was not detected in any of the organs not injected with Ad35 vectors. These results suggest that Ad35 vectors are suitable for gene delivery by direct administration to organs.

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Efficient gene transfer into human CD34+ cells by an adenovirus type 35 vector

Cited by 83 publications

References 42 publications

Development of fiber-substituted adenovirus vectors containing foreign peptides in the adenovirus serotype 35 fiber knob

Development of fiber-substituted adenovirus vectors containing foreign peptides in the adenovirus serotype 35 fiber knob

Optimization of adenovirus serotype 35 vectors for efficient transduction in human hematopoietic progenitors: comparison of promoter activities

Adenovirus serotype 35 vector-mediated transduction following direct administration into organs of nonhuman primates

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