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

Sakurai, F; Mizuguchi, H; Hayakawa, T

doi:10.1038/sj.gt.3301959

Cited by 88Virus-based gene therapy researchRNA Interference and Gene DeliveryHematopoietic Stem Cell Transplantation

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

Sakurai, F, Mizuguchi, H, Hayakawa, T·2003·Gene Therapy

DOI 10.1038/sj.gt.3301959

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Abstract

Efficient gene transfer into human hematopoietic stem cells (HSCs) is the most important requirement for gene therapy of hematopoietic disorders and for study of the hematopoietic system. An adenovirus (Ad) vector based on the Ad serotype 5 (Ad5) is known to transduce HSCs, including CD34(+) cells, with very low efficiency because of low-level expression of its primary receptor, coxsackievirus and adenovirus receptor (CAR). In the present study, we developed a recombinant Ad vector composed of the whole Ad serotype 35 (Ad35), which recognizes an unidentified receptor different from CAR for its infection. A transduction study showed that the Ad35-based vectors exhibit a higher transduction efficiency in human CD34(+) cells than the conventional Ad5 vectors and the Ad5F35 vectors, which are fiber-substituted Ad5 vectors containing Ad35 fiber proteins. The mean of fluorescence intensity in the CD34(+) cells transduced with the Ad35 vectors was 12-76 and 1.4-3 times higher than that in the cells transduced with the Ad5 and Ad5F35 vectors, respectively. The percentages of green fluorescent protein (GFP)-positive CD34(+) cells by transduction with Ad35, Ad5, and Ad5F35 vectors expressing GFP at 300 PFU/cell were 53%, 5%, and 52%, respectively, suggesting that Ad35 vectors mediate a more efficient gene transfer into human CD34(+) cells than Ad5 and Ad5F35 vectors, although the percentage of transduced cells was similar between Ad35 and Ad5F35 vectors. The Ad vector based on Ad35 could be very useful in gene therapy for blood disorders and gene transfer experiments using HSCs.

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Authors: Sakurai, F., Mizuguchi, H., & Hayakawa, T.
Affiliations: National Institute of Health Sciences (JP)
ORCID: Sakurai, F
Mizuguchi, H
Venue: Gene Therapy
Publisher: Springer Science and Business Media LLC
Published: 2003-05-30
Volume: 10
Issue: 12
Pages: 1041-1048
ISSN: 0969-7128 (ISSN-L)
1476-5462
DOI: 10.1038/sj.gt.3301959
OpenAlex: W1994007686
Cited by: 88
References: 44
Citations by year: 2026: 1 · 2025: 1 · 2024: 1 · 2023: 2 · 2021: 2 · 2020: 1 · 2017: 2 · 2016: 3 · 2015: 1 · 2014: 2 · 2013: 2 · 2012: 3
FWCI: 5.87
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Gene Therapy (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
Keywords: hematopoietic stem cells, CD34+ cells, gene transfer efficiency, adenoviral vector, coxsackievirus and adenovirus receptor, transduction
MeSH terms: Adenoviridae, Genetic Vectors, Hematopoietic Stem Cells, Humans, Luciferases, Luminescent Proteins, Transduction, Genetic, Gene Transfer Techniques, Antigens, CD34, Green Fluorescent Proteins

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

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