Construction and replication of an adeno-associated virus expression vector that contains human β-globin cDNA

Ohi, Seigo; Dixit, Mallika; Tillery, M.Kelly; Plonk, Steven G.

doi:10.1016/0378-1119(90)90018-m

Cited by 14 publications

(6 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A wide range of genes have been expressed from AAV vectors including neo, cat, and lacZ marker genes TRATSCHIN et al 1984b;LEBKOWSKI et al 1988;MURO-CACHO et al 1992;KApPLITI et al 1994;FLOTIE et al 1992;ZHOU et al 1993ZHOU et al , 1994GOODMAN et al 1994;LAFACE et al 1988;PODSAKOFF et al 1994;RUSSEL et al 1994), human tyrosine hydroxylase II cDNA (KAPLITI et al 1994), neuropeptide Y (Wu et al 1994), human glucocerebrosidase and arylsulfatase A (WEI et al 1994), CFTR (FLOTIE et al 1993 a,b;FLOTIE 1993), }' globin (WALSH et al 1992(WALSH et al , 1993MILLER et al 1993aMILLER et al ,b, 1994 f3 globin cDNA (DIXIT et al 1991;OHI et al 1989), antisense H IV-L TR neo (CHATIERJEE et al 1992) antisense IX-globin neo (PONNAZHAGAN et al 1994).…”

Section: Adeno-associated Virus Vectors For Gene Therapymentioning

confidence: 97%

Biology of Adeno-associated Virus

Berns

Giraud

1996

Current Topics in Microbiology and Immunology

199

173

View full text Add to dashboard Cite

Section: Adeno-associated Virus Vectors For Gene Therapymentioning

confidence: 97%

Biology of Adeno-associated Virus

Berns

Giraud

1996

Current Topics in Microbiology and Immunology

199

173

View full text Add to dashboard Cite

“…As our expertise lies on adeno-associated virus (AAV)-mediated gene therapy (Ohi, 1990;Dixit, 1991;Ohi, 1996), the vector containing IGF-1 could be constructed and used for muscle and bone gene therapy in space. The adeno-associated virus, serotype 2 (AAV2), is a human parvovirus, which contains a linear single-stranded DNA of 4,675 nucleotides (nt), having broad host-range and tissue-specificity (Rose, 1974;Berns, 1984).…”

Section: Discussionmentioning

confidence: 99%

“…This non-pathogenicity of AAV2, compared with other vectors, is particularly important for the space program, because of the enclosed environment in spaceships. Exploiting these advantages of AAV2, starting in 1985, we constructed recombinant AAVs (rAAVs) that harbor human globin genes as well as an anti-HIV-1 gag ribozyme (anti-gag Rz) for eventual use in gene therapies of the hemoglobinopathies, β-thalassemia and sickle cell disease, and AIDS, respectively (Ohi, 1990;Dixit, 1991;Ohi, 1996;Ohi, 1999). Many laboratories worldwide are now using the raav system for various gene therapy projects with promising results (Flannery, 1997;Kay, 2000;Wang, 2000).…”

Section: Discussionmentioning

confidence: 99%

The Hematopoietic Stem Cell Therapy for Exploration of Deep Space

Ohi¹,

Roach²,

Ramsahai³

et al. 2004

AIP Conference Proceedings

Self Cite

View full text Add to dashboard Cite

Astronauts experience severe/invasive disorders caused by space environments. These include hematological and cardiac abnormalities, bone and muscle losses, immunodeficiency, neurological disorders and cancer. Exploiting the extraordinary plasticity of hematopoietic stem cells (HSCs), which differentiate not only to all types of blood cells, but also to various tissues, including muscle, bone, skin, liver, and neuronal cells, we advanced a hypothesis that some of the space-caused disorders might be amenable to hematopoietic stem cell therapy (HSCT) so as to maintain astronauts' homeostasis. If this were achievable, the HSCT could promote human exploration of deep space. Using mouse models of human anemia (β-thalassemia) and spaceflight (hindlimb suspension unloading system), we have obtained feasibility results of HSCT for space anemia, muscle loss, and immunodeficiency. For example, the β-thalassemic mice were successfully transplanted with isologous HSCs, resulting in chimerism of hemoglobin species and alleviation of the hemoglobinopathy. In the case of HSCT for muscle loss, β-galactosidase-marked HSCs, which were prepared from βgalactosidase-transgenic mice, were detected by the X-gal wholemount staining procedure in the hindlimbs of unloaded mice following transplantation. Histochemical and physical analyses indicated structural contribution of HSCs to the muscle. To investigate HSCT for immunodeficiency, β-galactosidase-transformed Escherichia coli was used as the reporter bacteria, and infected to control and the hindlimb suspended mice. Results of the X-gal stained tissues indicated that the HSCT could help eliminate the E. coli infection. In an effort to facilitate the HSCT in space, growth of HSCs has been optimized in the NASA Rotating Wall Vessel (RWV) culture systems, including Hydrodynamic Focusing Bioreactor (HFB).

show abstract

“…[1][2][3] These diseases may be amenable to corrective gene therapy with normal globin genes. 9,10 The AAV serotype 2 (AAV2) is a human parvovirus which contains a linear single-stranded DNA of 4675 nucleotides (nt) having broad host-range and tissue specificity. While the recombinant retroviral system is most advanced in this endeavor, achieving expression of the HBB in bone marrow transplanted animals, 4,5,7 the mutagenic/carcinogenic nature of retroviruses per se might pose a potential hazard in clinical settings.…”

Section: Introductionmentioning

confidence: 99%

“…9,10 The construct efficiently expressed human -globin-encoding mRNAs in 293, KB (human oral epidermoid carcinoma cell line), and K562 (human erythroleukemia cell line) cells following infection. 9,10 The construct efficiently expressed human -globin-encoding mRNAs in 293, KB (human oral epidermoid carcinoma cell line), and K562 (human erythroleukemia cell line) cells following infection.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Human Globin Polypeptides Mediated by Recombinant Adeno-Associated Virus Vectors††Abstract published in the 36th Annual Meeting of the American Society of Hematology, December 2, 1994; Blood1994, 84, 263a. X Abstract published in Advance ACS Abstracts, January 1, 1996

Ohi

Kim

1996

Journal of Pharmaceutical Sciences

Self Cite

View full text Add to dashboard Cite

Adeno-associated virus, serotype 2 (AAV2)-based chimeric plasmids that harbored a near-full-length human alpha- or beta-globin cDNA were constructed. The cDNAs were spliced into an AAV plasmid, pAAV delta K, downstream from the viral P40 promoter, substituting the capsid gene region. The correctness of the insertion with regard to the transcription polarity was ascertained by both restriction enzyme analysis and DNA sequencing. One of the constructs, pAAVcHBBLCR, contained the erythroid-specific enhancer elements, the locus control region, HS1 and HS2, to ensure an efficient and tissue-specific gene expression. Use of a defective complementing helper, pAVXB (Dixit, M.; et al. Gene 1991, 104, 253-257.) and adenovirus 2 made it possible to prepare recombinant AAVs (rAAVs). Infection of human 293 cells (embryonal kidney cell line) with the resultant rAAV (AAVcHBB) and cotransfection of mouse erythroleukemia (MEL) cells with the beta-globin construct (pAAVcHBBLCR) and an alpha-globin construct (pAAVcHAB) triggered efficient synthesis of human globin polypeptides in the cells, as analyzed by biochemical and immunohistochemical means. The LCR made the construct respond to an inducer, N,N-hexamethylenebisacetamide, the amount of expressed human beta-globin reaching a similar level as the endogenous mouse beta-globin in MEL cells. Electrotransfection of mouse bone marrow hematopoietic stem/progenitor cells with the constructs dramatically increased the number of benzidine-positive cells in liquid suspension culture, indicating expression and synthesis of a human hemoglobin in these cells. Thus, the rAAV constructs may be useful for gene therapy of hemoglobinopathies.

show abstract

Construction and replication of an adeno-associated virus expression vector that contains human β-globin cDNA

Cited by 14 publications

References 11 publications

Biology of Adeno-associated Virus

Biology of Adeno-associated Virus

The Hematopoietic Stem Cell Therapy for Exploration of Deep Space

Synthesis of Human Globin Polypeptides Mediated by Recombinant Adeno-Associated Virus Vectors††Abstract published in the 36th Annual Meeting of the American Society of Hematology, December 2, 1994; Blood1994, 84, 263a. X Abstract published in Advance ACS Abstracts, January 1, 1996

Contact Info

Product

Resources

About