Development and analysis of retroviral vectors expressing human factor VIII as a potential gene therapy for hemophilia A.


:To develop a potential gene therapy strategy for the treatment of hemophilia A, we constructed several retroviral vectors expressing a B-domain-deleted factor VIII (FVIII) cDNA. We confirmed previous reports that when the FVIII cDNA is inserted into a retroviral vector, the vector mRNA is decreased resulting in significantly (100- to 1,000-fold) lower vector titers. In an attempt to overcome this inhibition we pursued two independent strategies. First, site-directed mutagenesis was employed to change the structure of a putative 1.2-kb FVIII RNA inhibitory sequence (INS). Second, the FVIII gene was transcribed from a retroviral vector containing a 5' intron. Results demonstrated that the intron increased FVIII expression up to 20-fold and viral titer up to 40-fold but conservative mutagenesis of the putative FVIII INS region failed to yield a significant increase in FVIII expression or titer. Using the improved FVIII splicing vector, we transduced a variety of cell types and were able to demonstrate relatively high FVIII expression (10-60 ng of FVIII/10(6) cells/24 hr). These results underscore the usefulness of these transduced cell types for potential in vivo delivery of FVIII.


Hum Gene Ther


Human gene therapy


Chuah MK,VandenDriessche T,Morgan RA




Has Abstract


1995-11-01 00:00:00












  • Factors associated with induced chronic inflammation in mdx skeletal muscle cause posttranslational stabilization and augmentation of extrasynaptic sarcolemmal utrophin.

    abstract::Chronic inflammation in tibialis anterior muscles of mdx mice was produced by a single injection of a recombinant adenovirus vector (AV) expressing an immunogenic beta-galactosidase (beta-gal). In regions of intense beta-gal staining, mononuclear infiltrates abounded, and muscle fibers showed strong extrasynaptic utro...

    journal_title:Human gene therapy

    pub_type: 杂志文章


    authors: Waheed I,Gilbert R,Nalbantoglu J,Guibinga GH,Petrof BJ,Karpati G

    更新日期:2005-04-01 00:00:00

  • Liver bypass significantly increases the transduction efficiency of recombinant adenoviral vectors in the lung, intestine, and kidney.

    abstract::Recombinant adenoviruses have great potential as gene delivery systems because of their ability to infect a wide range of target cells. However, systemic delivery of viral vectors to tissues other than liver and spleen has been inefficient because of the rapid clearance of the circulating virus by the liver. In the pr...

    journal_title:Human gene therapy

    pub_type: 杂志文章


    authors: Ye X,Jerebtsova M,Ray PE

    更新日期:2000-03-01 00:00:00

  • Bone Marrow Mesenchymal Stem Cells-Derived Exosomal MicroRNA-150-3p Promotes Osteoblast Proliferation and Differentiation in Osteoporosis.

    abstract::At present, much more studies have focused on the role of microRNAs in osteoporosis, but the more specific role of microRNA-150-3p (miR-150-3p) in osteoporosis still needs full exploration. We aim at investigating the role of miR-150-3p in osteoporosis and at exploring the related mechanisms. Bone marrow mesenchymal s...

    journal_title:Human gene therapy

    pub_type: 杂志文章


    authors: Qiu M,Zhai S,Fu Q,Liu D

    更新日期:2021-01-22 00:00:00

  • Bone-marrow-derived mesenchymal stem cells promote proliferation and neuronal differentiation of Niemann-Pick type C mouse neural stem cells by upregulation and secretion of CCL2.

    abstract::Niemann-Pick type C (NP-C) disease is a neurodegenerative disorder characterized neuropathologically by ballooned neurons distended with lipid storage and widespread neuronal loss. Neural stem cells (NSC) derived from NP-C disease models have decreased ability for self-renewal and neuronal differentiation. Investigati...

    journal_title:Human gene therapy

    pub_type: 杂志文章


    authors: Lee H,Kang JE,Lee JK,Bae JS,Jin HK

    更新日期:2013-07-01 00:00:00

  • Adipose tissue as a novel target for in vivo gene transfer by adeno-associated viral vectors.

    abstract::Traditionally, skeletal muscle and liver are the preferred target organs for gene transfer to supply a transgene product into the systemic circulation. In this respect, adipose tissue presents a number of attractive features. However, adipose tissue transduction in vivo has not been feasible by conventional methods. T...

    journal_title:Human gene therapy

    pub_type: 杂志文章


    authors: Mizukami H,Mimuro J,Ogura T,Okada T,Urabe M,Kume A,Sakata Y,Ozawa K

    更新日期:2006-09-01 00:00:00

  • Adenoviral gene transfer of sphingosine kinase 1 protects heart against ischemia/reperfusion-induced injury and attenuates its postischemic failure.

    abstract::Sphingosine kinase 1 (SPK1) has been identified as a central mediator of ischemia preconditioning and plays a protective role in ischemia/reperfusion (I/R)-induced cardiomyocyte death. In the present study, we investigated the protective effect of adenovirus-mediated SPK1 gene (Ad-SPK1) transfer on I/R-induced cardiac...

    journal_title:Human gene therapy

    pub_type: 杂志文章


    authors: Duan HF,Wang H,Yi J,Liu HJ,Zhang QW,Li LB,Zhang T,Lu Y,Wu CT,Wang LS

    更新日期:2007-11-01 00:00:00

  • Randomized Clinical Trials of Gene Transfer for Heart Failure with Reduced Ejection Fraction.

    abstract::Despite improvements in drug and device therapy for heart failure, hospitalization rates and mortality have changed little in the past decade. Randomized clinical trials using gene transfer to improve function of the failing heart are the focus of this review. Four randomized clinical trials of gene transfer in heart ...

    journal_title:Human gene therapy

    pub_type: 杂志文章,评审


    authors: Penny WF,Hammond HK

    更新日期:2017-05-01 00:00:00

  • Antigen-specific tolerance of human alpha1-antitrypsin induced by helper-dependent adenovirus.

    abstract::As efficient and less toxic virus-derived gene therapy vectors are developed, a pressing problem is to avoid immune response to the therapeutic gene product. Secreted therapeutic proteins potentially represent a special problem, as they are readily available to professional antigen-presenting cells throughout the body...

    journal_title:Human gene therapy

    pub_type: 杂志文章


    authors: Cerullo V,McCormack W,Seiler M,Mane V,Cela R,Clarke C,Rodgers JR,Lee B

    更新日期:2007-12-01 00:00:00

  • IL-6 production by retrovirus packaging cells and cultured bone marrow cells.

    abstract::Retrovirus integration into the host cell genome occurs most efficiently in replicating cells. In agreement with this notion, it was observed that the efficiency with which hemopoietic stem cells (HSC) can be transduced is greatly enhanced when the hemopoietic growth factor (HGF) interleukin 3 (IL-3) is added to co-cu...

    journal_title:Human gene therapy

    pub_type: 杂志文章


    authors: Einerhand MP,Bakx TA,Valerio D

    更新日期:1991-01-01 00:00:00

  • Hearing on the possible uses and misuses of genetic information.

    abstract::In summary, I will reiterate the five points I would like to leave with you today: First, the biological revolution has extraordinary power to do good. As long as the use of our new genetic knowledge is guided by the traditional ideals of the healing professions--to help improve the human condition without doing harm-...

    journal_title:Human gene therapy

    pub_type: 杂志文章


    authors: Healy B

    更新日期:1992-02-01 00:00:00

  • Fibroblast growth factor 2-retargeted adenoviral vectors exhibit a modified biolocalization pattern and display reduced toxicity relative to native adenoviral vectors.

    abstract::Targeted vectors provide a number of advantages for systemic and local gene delivery strategies. Several groups have investigated the utility of using various ligands to alter the tropism of adenovirus (Ad) vectors. We have previously demonstrated that fibroblast growth factor (FGF) ligands can specifically target DNA...

    journal_title:Human gene therapy

    pub_type: 杂志文章


    authors: Printz MA,Gonzalez AM,Cunningham M,Gu DL,Ong M,Pierce GF,Aukerman SL

    更新日期:2000-01-01 00:00:00

  • Simplified retroviral vector gcsap with murine stem cell virus long terminal repeat allows high and continued expression of enhanced green fluorescent protein by human hematopoietic progenitors engrafted in nonobese diabetic/severe combined immunodeficien

    abstract::Despite efforts toward improvements in retrovirus-mediated gene transfer, stable high-level expression of a therapeutic gene in human hematopoietic stem cells remains a great challenge. We have evaluated the efficiency of different viral long terminal repeats (LTRs) in long-term expression of a transgene in vivo, usin...

    journal_title:Human gene therapy

    pub_type: 杂志文章


    authors: Kaneko S,Onodera M,Fujiki Y,Nagasawa T,Nakauchi H

    更新日期:2001-01-01 00:00:00

  • A genetically engineered spleen necrosis virus-derived retroviral vector that displays the HIV type 1 glycoprotein 120 envelope peptide.

    abstract::We reported that SNV-derived retroviral vectors, which display single-chain antibodies on the viral surface, enable cell type-specific gene delivery into various human cells. In particular, the SNV cell type-specific gene delivery vector system appears to be well suited to transduce genes into cells of the human hemat...

    journal_title:Human gene therapy

    pub_type: 杂志文章


    authors: Jiang A,Fisher H,Pomerantz RJ,Dornburg R

    更新日期:1999-11-01 00:00:00

  • Enhanced gene expression conferred by stepwise modification of a nonprimate lentiviral vector.

    abstract::The practical application of gene transfer as a treatment for genetic diseases such as cystic fibrosis or hemophilia has been hindered, in part, by low efficiencies of vector delivery and transgene expression. We demonstrated that a feline immunodeficiency virus (FIV)-based lentiviral vector pseudotyped with the envel...

    journal_title:Human gene therapy

    pub_type: 杂志文章


    authors: Sinn PL,Goreham-Voss JD,Arias AC,Hickey MA,Maury W,Chikkanna-Gowda CP,McCray PB Jr

    更新日期:2007-12-01 00:00:00

  • Cellular Therapies for Muscular Dystrophies: Frustrations and Clinical Successes.

    abstract::Cell-based therapy for muscular dystrophies was initiated in humans after promising results obtained in murine models. Early trials failed to show substantial clinical benefit, sending researchers back to the bench, which led to the discovery of many hurdles as well as many new venues to optimize this therapeutic stra...

    journal_title:Human gene therapy

    pub_type: 杂志文章,评审


    authors: Negroni E,Bigot A,Butler-Browne GS,Trollet C,Mouly V

    更新日期:2016-02-01 00:00:00

  • Gene silencing of NALP3 protects against liver ischemia-reperfusion injury in mice.

    abstract::Liver ischemia-reperfusion (I/R) injury is a multifactorial process that affects graft function after liver transplantation. Inflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β, and IL-18, have been shown to play key roles in the pathophysiology of liver I/R injury. Studies have in...

    journal_title:Human gene therapy

    pub_type: 杂志文章


    authors: Zhu P,Duan L,Chen J,Xiong A,Xu Q,Zhang H,Zheng F,Tan Z,Gong F,Fang M

    更新日期:2011-07-01 00:00:00

  • Improved titers of retroviral vectors from the human FLYRD18 packaging cell line in serum- and protein-free medium.

    abstract::The influence of serum on the production of retroviral vectors by the HT1080 human fibrosarcoma-derived packaging cell line FLYRD18 was investigated. A fourfold increase in virus titer was observed under serum-free conditions, as compared with medium supplemented with 10% fetal calf serum. A similar improvement was al...

    journal_title:Human gene therapy

    pub_type: 杂志文章


    authors: Gerin PA,Gilligan MG,Searle PF,Al-Rubeai M

    更新日期:1999-08-10 00:00:00

  • Efficient serum-free retroviral gene transfer into primitive human hematopoietic progenitor cells by a defined, high-titer, nonconcentrated vector-containing medium.

    abstract::Defined serum-free conditions have great conceptual advantages for the biological safety and standardization of clinical gene transfer into hematopoietic stem cells. In the only study reported to date, Sekhar et al. achieved low serum conditions by a complex concentration procedure of a retroviral supernatant initiall...

    journal_title:Human gene therapy

    pub_type: 杂志文章


    authors: Glimm H,Flügge K,Möbest D,Hofmann VM,Postmus J,Henschler R,Lange W,Finke J,Kiem HP,Schulz G,Rosenthal F,Mertelsmann R,von Kalle C

    更新日期:1998-04-10 00:00:00

  • Corrective transduction of human epidermal stem cells in laminin-5-dependent junctional epidermolysis bullosa.

    abstract::Laminin-5 is composed of three distinct polypeptides, alpha3, beta3, and gamma2, which are encoded by three different genes, LAMA3, LAMB3, and LAMC2, respectively. We have isolated epidermal keratinocytes from a patient presenting with a lethal form of junctional epidermolysis bullosa characterized by a homozygous mut...

    journal_title:Human gene therapy

    pub_type: 杂志文章


    authors: Dellambra E,Vailly J,Pellegrini G,Bondanza S,Golisano O,Macchia C,Zambruno G,Meneguzzi G,De Luca M

    更新日期:1998-06-10 00:00:00

  • Stem-Cell Therapy Advances in China.

    abstract::Stem-cell therapy is a promising method for treating patients with a wide range of diseases and injuries. Increasing government funding of scientific research has promoted rapid developments in stem-cell research in China, as evidenced by the substantial increase in the number and quality of publications in the past 5...

    journal_title:Human gene therapy

    pub_type: 杂志文章,评审


    authors: Hu L,Zhao B,Wang S

    更新日期:2018-02-01 00:00:00

  • Intravenous RMP-7 increases delivery of ganciclovir into rat brain tumors and enhances the effects of herpes simplex virus thymidine kinase gene therapy.

    abstract::Herpes simplex virus thymidine kinase (HSV-tk) gene therapy for brain tumors depends on ganciclovir (GCV) and its transport across the blood-brain tumor barrier (BBTB). We examined whether RMP-7, the bradykinin analog and potent BBTB permeabilizer, could enhance the efficacy of GCV treatment of brain tumors by increas...

    journal_title:Human gene therapy

    pub_type: 杂志文章


    authors: LeMay DR,Kittaka M,Gordon EM,Gray B,Stins MF,McComb JG,Jovanovic S,Tabrizi P,Weiss MH,Bartus R,Anderson WF,Zlokovic BV

    更新日期:1998-05-01 00:00:00

  • Direct comparison of steady-state marrow, primed marrow, and mobilized peripheral blood for transduction of hematopoietic stem cells in dogs.

    abstract::The optimal stem cell source for stem cell gene therapy has not been defined. Most gene transfer studies have used peripheral blood or marrow repopulating cells collected after administration of granulocyte colony-stimulating factor and stem cell factor (G-CSF/SCF). For clinical applications, however, growth factor ad...

    journal_title:Human gene therapy

    pub_type: 杂志文章


    authors: Thomasson B,Peterson L,Thompson J,Goerner M,Kiem HP

    更新日期:2003-11-20 00:00:00

  • A mutant Tat protein provides strong protection from HIV-1 infection in human CD4+ T cells.

    abstract::Here we show potent inhibition of HIV-1 replication in a human T cell line and primary human CD4(+) cells by expressing a single antiviral protein. Nullbasic is a mutant form of the HIV-1 Tat protein that was previously shown to strongly inhibit HIV-1 replication in nonhematopoietic cell lines by targeting three steps...

    journal_title:Human gene therapy

    pub_type: 杂志文章


    authors: Apolloni A,Lin MH,Sivakumaran H,Li D,Kershaw MH,Harrich D

    更新日期:2013-03-01 00:00:00

  • Retrovirus-mediated gene transfer of ornithine-delta-aminotransferase into keratinocytes from gyrate atrophy patients.

    abstract::Gyrate atrophy is a progressive blindness associated with deficiency of ornithine aminotransferase (OAT). The strategy of using an autologous keratinocyte graft, modified to express high levels of OAT as an ornithine-catabolizing skin-based enzyme sink, is investigated. Two OAT-containing retroviral vectors were const...

    journal_title:Human gene therapy

    pub_type: 杂志文章


    authors: Jensen TG,Sullivan DM,Morgan RA,Taichman LB,Nussenblatt RB,Blaese RM,Csaky KG

    更新日期:1997-11-20 00:00:00

  • Exploring the Potential Feasibility of Intra-Articular Adeno-Associated Virus-Mediated Gene Therapy for Hemophilia Arthropathy.

    abstract::Hemophilia arthropathy (HA) represents the majority of morbidity in severe hemophilia patients, especially in resource-limited countries. Adeno-associated virus (AAV)-mediated gene therapy is showing promise for managing hemophilia. However, patients with neutralizing antibodies (NAbs) against AAV, and inhibitors to c...

    journal_title:Human gene therapy

    pub_type: 杂志文章


    authors: Zhang F,Yan X,Li M,Hua B,Xiao X,Monahan PE,Sun J

    更新日期:2020-04-01 00:00:00

  • Immune responses against replication-deficient adenovirus inhibit ovalbumin-specific allergic reactions in mice.

    abstract::Replication-deficient adenovirus vector (Ad) is one of the most efficient gene transfer vehicles for human gene therapy. However, Ad is antigenic, known to evoke prominent inflammatory responses in vivo, and there are concerns that using Ad in patients with immune-mediated disorders (allergy and autoimmune diseases) m...

    journal_title:Human gene therapy

    pub_type: 杂志文章


    authors: Suzuki M,Suzuki S,Yamamoto N,Komatsu S,Inoue S,Hashiba T,Nishikawa M,Ishigatsubo Y

    更新日期:2000-04-10 00:00:00

  • Addition of a single E2 binding site to the human papillomavirus (HPV) type 16 long control region enhances killing of HPV positive cells via HPV E2 protein-regulated herpes simplex virus type 1 thymidine kinase-mediated suicide gene therapy.

    abstract::Human papillomavirus type 16 (HPV16) is associated with the development of anogenital cancers and their precursor lesions, intraepithelial neoplasia. Treatment strategies against HPV-induced intraepithelial neoplasia are not HPV specific and mostly consist of physical removal or ablation of lesions. We had previously ...

    journal_title:Human gene therapy

    pub_type: 杂志文章


    authors: Sharma R,Palefsky JM

    更新日期:2010-07-01 00:00:00

  • Helper-dependent adenoviral vectors containing modified fiber for improved transduction of developing and mature muscle cells.

    abstract::Adenoviruses (Ads) have shown great utility as vectors for the delivery of genes to mammalian cells, partly because of their ability to infect a wide range of different cell types independent of the replicative state of the cell. However, Ads do not transduce mature muscle efficiently because of low levels of the natu...

    journal_title:Human gene therapy

    pub_type: 杂志文章


    authors: Bramson JL,Grinshtein N,Meulenbroek RA,Lunde J,Kottachchi D,Lorimer IA,Jasmin BJ,Parks RJ

    更新日期:2004-02-01 00:00:00

  • The effects of human serum and cerebrospinal fluid on retroviral vectors and packaging cell lines.

    abstract::Human serum is known to inactivate many retroviruses, including murine leukemia viruses (MLV). Exposure of vectors based on MLV to human serum components would presumably decrease the efficiency of gene transfer in vivo. Human serum also lyses xenogeneic cells, which would affect the survival of retroviral vector pack...

    journal_title:Human gene therapy

    pub_type: 杂志文章


    authors: Russell DW,Berger MS,Miller AD

    更新日期:1995-05-01 00:00:00

  • Ultrasound enhances gene delivery of human factor IX plasmid.

    abstract::Delivery of plasmid DNA can be enhanced by treatment with ultrasound (US); acoustic cavitation appears to play an important role in the process. Ultrasound contrast agents (UCAs; stabilized microbubbles) nucleate acoustic cavitation, and lower the acoustic pressure threshold for inertial cavitation occurrence. Fifty m...

    journal_title:Human gene therapy

    pub_type: 杂志文章


    authors: Miao CH,Brayman AA,Loeb KR,Ye P,Zhou L,Mourad P,Crum LA

    更新日期:2005-07-01 00:00:00