Transient expression of genes transferred in vivo into heart using first-generation adenoviral vectors: role of the immune response.


:Gene therapy for heart diseases requires availability of an efficient vector for gene transfer into myocardium. Recombinant adenovirus expressing the Escherichia coli beta-galactosidase (beta-Gal) gene was shown to infect rat cardiocytes efficiently in vivo. However, a time course of gene expression showed that transgene expression was maximal during the first week following injection, then declined and disappeared by day 21. An immunosuppressive treatment prolonged beta-Gal expression for at least 21 days. On the contrary, a preimmunization of the animals by two intraperitoneal injections of the vector led to a decreased transgene expression 48 hr after intramyocardial injection and to a barely detectable expression at the sixth day. Appearance of adenovirus neutralizing antibodies in preimmunized animals could have contributed to such a refractoriness to further adenoviral infection. Finally, a neonatal intrathymic injection of the vector was able to induce long-term LacZ expression for more than 2 months after heart injection, although neutralizing as well as anti-beta-Gal antibodies were detected in sera of the animals. These results indicate that an immune response against first-generation replication-defective adenoviral vectors is a major cause of transient transgene expression, a cellular response being most probably responsible for ablation of transgene expression in immunocompetent animals.


Hum Gene Ther


Human gene therapy


Gilgenkrantz H,Duboc D,Juillard V,Couton D,Pavirani A,Guillet JG,Briand P,Kahn A




Has Abstract


1995-10-01 00:00:00












  • Thymidine kinase gene modified bone marrow mesenchymal stem cells as vehicles for antitumor therapy.

    abstract::Bone marrow mesenchymal stem cells (BMSCs) represent an important source of cells for tissue repair. The tropism of these cells to the sites of injury and tumors has been well established. Their tumor-homing properties make BMSCs good candidates as antitumor agent delivery vehicles. In this study, we showed that BMSCs...

    journal_title:Human gene therapy

    pub_type: 杂志文章


    authors: Song C,Xiang J,Tang J,Hirst DG,Zhou J,Chan KM,Li G

    更新日期:2011-04-01 00:00:00

  • Coexpression of cytidine deaminase and mutant dihydrofolate reductase by a bicistronic retroviral vector confers resistance to cytosine arabinoside and methotrexate.

    abstract::The transfer of a drug resistance gene into hematopoietic cells is an approach being investigated to overcome the problem of myelosuppression produced by anticancer drugs. Chemotherapeutic agents are often given in combination in order to increase their effectiveness. Consequently, there is an advantage in designing v...

    journal_title:Human gene therapy

    pub_type: 杂志文章


    authors: Beauséjour CM,Le NL,Létourneau S,Cournoyer D,Momparler RL

    更新日期:1998-11-20 00:00:00

  • Safety, tolerability, and lack of antibody responses after administration of a PfCSP DNA malaria vaccine via needle or needle-free jet injection, and comparison of intramuscular and combination intramuscular/intradermal routes.

    abstract::Introduction of a new vaccine requires choosing a delivery system that provides safe administration and the desired level of immunogenicity. The safety, tolerability, and immunogenicity of three monthly 2.5-mg doses of a PfCSP DNA vaccine were evaluated in healthy volunteers as administered intramuscularly (IM) by nee...

    journal_title:Human gene therapy

    pub_type: 杂志文章


    authors: Epstein JE,Gorak EJ,Charoenvit Y,Wang R,Freydberg N,Osinowo O,Richie TL,Stoltz EL,Trespalacios F,Nerges J,Ng J,Fallarme-Majam V,Abot E,Goh L,Parker S,Kumar S,Hedstrom RC,Norman J,Stout R,Hoffman SL

    更新日期:2002-09-01 00:00:00

  • Maternal Therapy with Ad.VEGF-A165 Increases Fetal Weight at Term in a Guinea-Pig Model of Fetal Growth Restriction.

    abstract::In a model of growth-restricted sheep pregnancy, it was previously demonstrated that transient uterine artery VEGF overexpression can improve fetal growth. This approach was tested in guinea-pig pregnancies, where placental physiology is more similar to humans. Fetal growth restriction (FGR) was attained through peri-...

    journal_title:Human gene therapy

    pub_type: 杂志文章


    authors: Swanson AM,Rossi CA,Ofir K,Mehta V,Boyd M,Barker H,Ledwozyw A,Vaughan O,Martin J,Zachary I,Sebire N,Peebles DM,David AL

    更新日期:2016-12-01 00:00:00

  • The development and testing of retroviral vectors expressing trans-dominant mutants of HIV-1 proteins to confer anti-HIV-1 resistance.

    abstract::Trans-dominant mutants of human immunodeficiency virus type 1 (HIV-1) Tat and Rev are attractive candidates for use in gene therapy in the treatment of HIV-1 infections because both are essential for viral replication. Retroviral vectors were constructed to allow either Tat-inducible or Tat- and Rev-inducible expressi...

    journal_title:Human gene therapy

    pub_type: 杂志文章


    authors: Liem SE,Ramezani A,Li X,Joshi S

    更新日期:1993-10-01 00:00:00

  • Poor expression of MDR1 transgene in HeLa cells by bicistronic Moloney murine leukemia virus-based vector.

    abstract::Cotransfer of a therapeutic gene together with the human MDR1 gene provides an opportunity to increase the number of transduced marrow cells, expressing the therapeutic gene, by in vivo selection for MDR1. We have used an Lg-MDR1-IRES-neo (LgMIN) retroviral vector, containing MDR1 and neo genes, separated by the EMCV ...

    journal_title:Human gene therapy

    pub_type: 杂志文章


    authors: Zaboikin MM,Schuening FG

    更新日期:1998-10-10 00:00:00

  • Adenovirus-mediated transfer of an Na+/K+-ATPase beta1 subunit gene improves alveolar fluid clearance and survival in hyperoxic rats.

    abstract::Pulmonary edema is cleared via active Na(+) transport by alveolar epithelial Na(+)/K(+)-ATPases and Na(+) channels. Rats exposed to acute hyperoxia have a high mortality rate, decreased Na(+)/K(+)-ATPase function, and decreased alveolar fluid clearance (AFC). We hypothesized that Na(+)/K(+)-ATPase subunit gene overexp...

    journal_title:Human gene therapy

    pub_type: 杂志文章


    authors: Factor P,Dumasius V,Saldias F,Brown LA,Sznajder JI

    更新日期:2000-11-01 00:00:00

  • Endothelial Progenitor Cells as Shuttle of Anticancer Agents.

    abstract::Cell therapies are treatments in which stem or progenitor cells are stimulated to differentiate into specialized cells able to home to and repair damaged tissues. After their discovery, endothelial progenitor cells (EPCs) stimulated worldwide interest as possible vehicles to perform autologous cell therapy of tumors. ...

    journal_title:Human gene therapy

    pub_type: 杂志文章,评审


    authors: Laurenzana A,Margheri F,Chillà A,Biagioni A,Margheri G,Calorini L,Fibbi G,Del Rosso M

    更新日期:2016-10-01 00:00:00

  • Adenoviral gene therapy leads to rapid induction of multiple chemokines and acute neutrophil-dependent hepatic injury in vivo.

    abstract::Replication-deficient adenoviruses are known to induce acute injury and inflammation of infected tissues, thus limiting their use for human gene therapy. However, molecular mechanisms triggering this response have not been fully defined. To characterize this response, chemokine expression was evaluated in DBA/2 mice f...

    journal_title:Human gene therapy

    pub_type: 杂志文章


    authors: Muruve DA,Barnes MJ,Stillman IE,Libermann TA

    更新日期:1999-04-10 00:00:00

  • Use of Epstein-Barr virus nuclear antigen-1 in targeted therapy of EBV-associated neoplasia.

    abstract::To target expression of toxic genes to Epstein-Barr virus (EBV)-associated tumor cells, we have developed an EBV-driven enzyme prodrug system (EDEPS) that takes advantage of the trans-activating properties of EBNA1, a latent protein expressed in all EBV-containing cells, to direct expression of cytosine deaminase (CD)...

    journal_title:Human gene therapy

    pub_type: 杂志文章


    authors: Judde JG,Spangler G,Magrath I,Bhatia K

    更新日期:1996-03-20 00:00:00

  • Fas-Fas ligand interactions play a major role in effector functions of cytotoxic T lymphocytes after adenovirus vector-mediated gene transfer.

    abstract::Adenovirus vectors transduce liver hepatocytes with extreme efficiency; however, transgene expression is eliminated within 2 weeks. Extinction of transgene expression has been attributed to infiltrating cytotoxic T lymphocytes (CTLs) in the liver in a process that resembles a number of human diseases, including viral ...

    journal_title:Human gene therapy

    pub_type: 杂志文章


    authors: Chirmule N,Moscioni AD,Qian Y,Qian R,Chen Y,Wilson JM

    更新日期:1999-01-20 00:00:00

  • Mutated Ras-transfected, EBV-transformed lymphoblastoid cell lines as a model tumor vaccine for boosting T-cell responses against pancreatic cancer: a pilot trial.

    abstract::Genetically modified lymphoblastoid cell lines (LCL) have been shown to be an attractive alternative source of antigen-presenting cells for cancer vaccination in vitro. We tested their application in patients with pancreatic cancer in a phase I clinical trial. As a model tumor antigen, we selected the point-mutated (c...

    journal_title:Human gene therapy

    pub_type: 临床试验,杂志文章


    authors: Kubuschok B,Pfreundschuh M,Breit R,Hartmann F,Sester M,Gärtner B,König J,Murawski N,Held G,Zwick C,Neumann F

    更新日期:2012-12-01 00:00:00

  • Nuclease-deficient CRISPR-based approaches for in vitro and in vivo gene activation.

    abstract::CRISPR-based technology has been adapted to achieve a wide range of genome modifications including transcription regulation. The focus of this review is on the application of CRISPR-based platforms such as nuclease-deficient Cas9 and Cas12a, to achieve targeted gene activation. We review studies to date that have empl...

    journal_title:Human gene therapy

    pub_type: 杂志文章


    authors: Lek A,Ma K,Woodman K,Lek M

    更新日期:2021-01-15 00:00:00

  • Complete regression of large solid tumors using engineered drug-resistant hematopoietic cells and anti-CD137 immunotherapy.

    abstract::Combining chemotherapy and immunotherapy is problematic because chemotherapy can ablate the immune responses initiated by modulators of the immune system. We hypothesized that protection of immunocompetent cells from the toxic effects of chemotherapy, using drug resistance gene therapy strategies, would allow the comb...

    journal_title:Human gene therapy

    pub_type: 杂志文章


    authors: McMillin DW,Hewes B,Gangadharan B,Archer DR,Mittler RS,Spencer HT

    更新日期:2006-08-01 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

  • Inhibition of human immunodeficiency virus type 1 replication by nuclear chimeric anti-HIV ribozymes in a human T lymphoblastoid cell line.

    abstract::Human immunodeficiency virus (HIV) infection represents one of the most challenging systems for gene therapy. Thanks to the extended knowledge of the molecular biology of the HIV life cycle, many different strategies have been developed including transdominant modifications of HIV proteins, RNA decoys, antisense RNA, ...

    journal_title:Human gene therapy

    pub_type: 杂志文章


    authors: Michienzi A,Conti L,Varano B,Prislei S,Gessani S,Bozzoni I

    更新日期:1998-03-20 00:00:00

  • Stable transduction with lentiviral vectors and amplification of immature hematopoietic progenitors from cord blood of preterm human fetuses.

    abstract::Umbilical cord blood (CB) from the early gestational human fetus is recognized as a rich source of hematopoietic stem cells. To examine the value of fetal CB for gene therapy of inborn immunohematopoietic disorders, we tested the feasibility of genetic modification of CD34(+) cells from CB at weeks 24 to 34 of pregnan...

    journal_title:Human gene therapy

    pub_type: 杂志文章


    authors: Luther-Wyrsch A,Costello E,Thali M,Buetti E,Nissen C,Surbek D,Holzgreve W,Gratwohl A,Tichelli A,Wodnar-Filipowicz A

    更新日期:2001-03-01 00:00:00

  • Antitumor therapy based on cellular competition.

    abstract::A major obstacle for the efficacy of cancer gene therapy is the need to transduce a high proportion of tumor cells with genes that directly or indirectly cause their death. During the formation of certain organs, cells compete among themselves to colonize the whole tissue. We reasoned that cell competition could be us...

    journal_title:Human gene therapy

    pub_type: 杂志文章


    authors: Martinez-Quintanilla J,Cascallo M,Fillat C,Alemany R

    更新日期:2009-07-01 00:00:00

  • Assessment of AAV Vector Tropisms for Mouse and Human Pluripotent Stem Cell-Derived RPE and Photoreceptor Cells.

    abstract::Adeno-associated viral vectors are showing great promise as gene therapy vectors for a wide range of retinal disorders. To date, evaluation of therapeutic approaches has depended almost exclusively on the use of animal models. With recent advances in human stem cell technology, stem cell-derived retina now offers the ...

    journal_title:Human gene therapy

    pub_type: 杂志文章


    authors: Gonzalez-Cordero A,Goh D,Kruczek K,Naeem A,Fernando M,Kleine Holthaus SM,Takaaki M,Blackford SJI,Kloc M,Agundez L,Sampson RD,Borooah S,Ovando-Roche P,Mehat MS,West EL,Smith AJ,Pearson RA,Ali RR

    更新日期:2018-10-01 00:00:00

  • Retargeting adenovirus serotype 48 fiber knob domain by peptide incorporation.

    abstract::Adenovirus type 5 (Ad5) is a commonly used vector for gene therapy, but its efficacy is limited by high seroprevalence and off-target hepatic and splenic sequestration. In order to circumvent these limitations, the use of vectors derived from rare species adenoviruses is appealing. The opportunity to retarget rare spe...

    journal_title:Human gene therapy

    pub_type: 杂志文章


    authors: Coughlan L,Uusi-Kerttula H,Ma J,Degg BP,Parker AL,Baker AH

    更新日期:2014-04-01 00:00:00

  • Arterial gene transfer using pure DNA applied directly to a hydrogel-coated angioplasty balloon.

    abstract::Direct arterial gene transfer has been previously achieved using double-balloon catheters and perforated balloons, in most cases facilitated by the use of cationic liposomes or viral vectors. These gene delivery systems, however, have been compromised by issues relating to efficacy and/or safety, and furthermore requi...

    journal_title:Human gene therapy

    pub_type: 杂志文章


    authors: Riessen R,Rahimizadeh H,Blessing E,Takeshita S,Barry JJ,Isner JM

    更新日期:1993-12-01 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

  • FUT-175, a synthetic inhibitor of the complement pathway, protects against the inactivation of infectious retroviruses by human serum.

    abstract::Serum-induced inactivation of retroviruses is the most critical limitation for in vivo gene transfer therapy. To solve this problem, we searched for reagents that protect retroviruses from inactivation. The effects of the protease inhibitors FOY-007 and FOY-305 and of an inhibitor of the complement pathway FUT-175, al...

    journal_title:Human gene therapy

    pub_type: 杂志文章


    authors: Miyao Y,Ikenaka K,Kishima H,Tamura M,Nakamura K,Kurumi M,Hayakawa T,Shimizu K

    更新日期:1997-09-01 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

  • Aerosol delivery of a beta-galactosidase adenoviral vector to the lungs of rodents.

    abstract::Aerosol delivery of adenoviral vectors is of particular interest in regard to gene therapy for cystic fibrosis (CF), with potential advantages of more uniform respiratory delivery, a less invasive approach, and ease of repetition. The AdHCMVsp1LacZ (AdLacZ) adenoviral vector was used to evaluate the feasibility of aer...

    journal_title:Human gene therapy

    pub_type: 杂志文章


    authors: Katkin JP,Gilbert BE,Langston C,French K,Beaudet AL

    更新日期:1995-08-01 00:00:00

  • In vivo marking of spontaneous or vaccine-induced fibrosarcomas in the domestic house cat, using an adenoviral vector containing a bifunctional fusion protein, GAL-TEK.

    abstract::We evaluated the ability of a replication-deficient, recombinant adenoviral vector to transfer the bifunctional gene GAL-TEK, which expresses a marking/therapeutic gene product, to naturally occurring cat fibrosarcomas in situ. GAL-TEK contains an in-frame fusion of the bacterial LacZ gene for histochemical marking of...

    journal_title:Human gene therapy

    pub_type: 杂志文章


    authors: Marini FC 3rd,Cannon JP,Belmont JW,Shillitoe EJ,Lapeyre JN

    更新日期:1995-09-01 00:00:00

  • Augmentation of antitumor activity of a recombinant adeno-associated virus carcinoembryonic antigen vaccine with plasmid adjuvant.

    abstract::Recombinant adeno-associated virus 2 (rAAV) vectors have been successfully used for sustained expression of therapeutic genes. The potential of using rAAV as a cancer vaccine vector and the impact of a bacterial plasmid adjuvant on this activity were investigated. C57BL/6 mice received a single intramuscular injection...

    journal_title:Human gene therapy

    pub_type: 杂志文章


    authors: Ponnazhagan S,Mahendra G,Lima J,Aldrich WA,Jenkins CB,Ren C,Kumar S,Kallman L,Strong TV,Shaw DR,Triozzi PL

    更新日期:2004-09-01 00:00:00

  • Dystrophin gene repair in mdx muscle precursor cells in vitro and in vivo mediated by RNA-DNA chimeric oligonucleotides.

    abstract::Point mutations in the dystrophin gene cause dystrophin deficiency and muscular dystrophy in the mdx mouse and a subset of patients with Duchenne muscular dystrophy. As an approach to gene therapy for muscular dystrophies due to point mutations, we have studied the ability of RNA-DNA chimeric oligonucleotides (chimera...

    journal_title:Human gene therapy

    pub_type: 杂志文章


    authors: Bertoni C,Rando TA

    更新日期:2002-04-10 00:00:00

  • Soluble bone marrow stroma factors improve the efficiency of retroviral transfer of the human multidrug resistance 1 gene to human mobilized peripheral blood progenitor cells.

    abstract::Hematopoietic stem cells (HSCs) are a potential target for the retrovirus-mediated transfer of chemotherapeutic drug resistance genes. For integration of the proviral DNA in the HSC genome cell division is required. In the bone marrow (BM) hematopoiesis occurs in the vicinity of stroma cells. Soluble stroma components...

    journal_title:Human gene therapy

    pub_type: 杂志文章


    authors: Schiedlmeier B,Buss EC,Veldwijk MR,Zeller WJ,Fruehauf S

    更新日期:1999-06-10 00:00:00

  • Preclinical Evaluation of Chimeric Antigen Receptor-Modified T Cells Specific to Epithelial Cell Adhesion Molecule for Treating Colorectal Cancer.

    abstract::This is an erratum of the published paper "Preclinical Evaluation of Chimeric Antigen Receptor-Modified T Cells Specific to Epithelial Cell Adhesion Molecule for Treating Colorectal Cancer". There are some errors in figure 6C and 7C in the article due to authors' mistakes when preparing the figures. Specifically, repr...

    journal_title:Human gene therapy

    pub_type: 杂志文章


    authors: Wang W

    更新日期:2019-08-01 00:00:00