Cell entry targeting restricts biodistribution of replication-competent retroviruses to tumour tissue.

Abstract:

:Virotherapy is currently being developed for many different types of viruses including replication-competent murine leukaemia virus (MLV) as a novel tool in cancer therapy. However, there is the risk of insertional mutagenesis associated with this virus, making careful preclinical studies necessary before its first application in man. We have previously generated conditionally replication-competent MLV variants that require activation by tumour-associated proteases to become infectious. Here we analysed in a comparative study the spreading of non-targeted and of such tumour-targeted MLV variants to tumour and extratumoural organs in immunodeficient mice. Both virus types were able to efficiently infect tumour cells after systemic administration. The non-targeted virus, however, also infected extratumoural organs like bone marrow, spleen and liver efficiently. In contrast, the targeted viruses revealed in a quantitative analysis of virus spreading an up to 500-fold more selective infection of tumour tissue than the non-targeted virus. The data raise serious doubts about a safe clinical use of non-targeted MLV. Engineering the virus to become activatable by tumour-associated proteases can significantly improve the safety of MLV.

journal_name

Gene Ther

journal_title

Gene therapy

authors

Duerner LJ,Schwantes A,Schneider IC,Cichutek K,Buchholz CJ

doi

10.1038/gt.2008.92

subject

Has Abstract

pub_date

2008-11-01 00:00:00

pages

1500-10

issue

22

eissn

0969-7128

issn

1476-5462

pii

gt200892

journal_volume

15

pub_type

杂志文章
  • Injection of IL-12 gene-transduced dendritic cells into mouse liver tumor lesions activates both innate and acquired immunity.

    abstract::Dendritic cell (DC)-based vaccines have been applied clinically in the setting of advanced-stage cancer. To date, the clinical efficacy of these vaccines has been limited, possibly owing to the impairment of transferred DC function in cancer-bearing patients. In this study, we examined the therapeutic efficacy of inte...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3302941

    authors: Tatsumi T,Takehara T,Yamaguchi S,Sasakawa A,Miyagi T,Jinushi M,Sakamori R,Kohga K,Uemura A,Ohkawa K,Storkus WJ,Hayashi N

    更新日期:2007-06-01 00:00:00

  • Generation of human TRIM5alpha mutants with high HIV-1 restriction activity.

    abstract::Rhesus macaque tripartite motif (TRIM)5alpha potently inhibits early stages of human immunodeficiency virus (HIV)-1 replication, while the human orthologue has little effect on this virus. We used PCR-based random mutagenesis to construct a large library of human TRIM5alpha variants containing mutations in the PRYSPRY...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/gt.2010.40

    authors: Pham QT,Bouchard A,Grütter MG,Berthoux L

    更新日期:2010-07-01 00:00:00

  • Characterization of plasmid DNA transfer into mouse skeletal muscle: evaluation of uptake mechanism, expression and secretion of gene products into blood.

    abstract::The expression of naked plasmid DNA coding for firefly luciferase (pRSVluc) or a secreted protein, human-alpha-1-antitrypsin (pRcCMVhAAT) in mouse skeletal muscle was characterized following administration by an improved intramuscular injection technique. Injection guided by intense illumination along the longitudinal...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:

    authors: Levy MY,Barron LG,Meyer KB,Szoka FC Jr

    更新日期:1996-03-01 00:00:00

  • Co-injection of adenovirus expressing CTLA4-Ig prolongs adenovirally mediated lacZ reporter gene expression in the mouse retina.

    abstract::There is growing interest in gene delivery to the eye in order to develop gene therapy for the many ocular disorders which may be amenable to this approach. To date, recombinant adenoviruses (AV) have been the main vector used for gene delivery to anterior and posterior segments in animal models. As with delivery to o...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3300761

    authors: Ali RR,Reichel MB,Byrnes AP,Stephens CJ,Thrasher AJ,Baker D,Hunt DM,Bhattacharya SS

    更新日期:1998-11-01 00:00:00

  • Utility of Epstein-Barr virus-encoded small RNA promoters for driving the expression of fusion transcripts harboring short hairpin RNAs.

    abstract::To induce RNA interference (RNAi), either small interfering RNAs (siRNAs) are directly introduced into the cell or short hairpin RNAs (shRNAs) are expressed from a DNA vector. At present, shRNAs are commonly synthesized by RNA polymerase III (Pol III) promoters of the H1 and U6 RNAs. In this study, we designed and cha...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3303055

    authors: Choy EY,Kok KH,Tsao SW,Jin DY

    更新日期:2008-02-01 00:00:00

  • Fractionated radiation therapy in combination with adenoviral delivery of the cytosine deaminase gene and 5-fluorocytosine enhances cytotoxic and antitumor effects in human colorectal and cholangiocarcinoma models.

    abstract::Radiosensitization of human gastrointestinal tumors by 5-fluorouracil (5-FU) has been studied in vitro and clinically in human cancer therapy trials. The bacterial enzyme cytosine deaminase (CD) converts the nontoxic prodrug 5-fluorocytosine (5-FC) into 5-FU. Human colon cancer cells stably expressing CD have been sho...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3301196

    authors: Stackhouse MA,Pederson LC,Grizzle WE,Curiel DT,Gebert J,Haack K,Vickers SM,Mayo MS,Buchsbaum DJ

    更新日期:2000-06-01 00:00:00

  • Herpes simplex virus 1 recombinant virions exhibiting the amino terminal fragment of urokinase-type plasminogen activator can enter cells via the cognate receptor.

    abstract::Earlier this laboratory constructed a herpes simplex virus 1 recombinant (R5111) that carries a IL13 ligand inserted into glycoprotein D and can enter cells via the IL13Ralpha2 receptor commonly expressed on the surface of malignant glioma cells. In this report, we describe the properties of two recombinant viruses ca...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3302685

    authors: Kamiyama H,Zhou G,Roizman B

    更新日期:2006-04-01 00:00:00

  • Multiple systemic expression of human interferon-beta in mice can be achieved upon repeated administration of optimized pcTG90-lipoplex.

    abstract::The possibility of achieving multiple systemic expression of human interferon-beta in mice upon repeated intravenous administration of cationic liposome-DNA complex (lipoplex) was investigated. Lipoplexes containing the pentammonio lipid pcTG90 were first optimized by selecting the most efficient ratio of pcTG90 to ph...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3301289

    authors: Meyer O,Schughart K,Pavirani A,Kolbe HV

    更新日期:2000-09-01 00:00:00

  • Effective treatment of vascular endothelial growth factor refractory hindlimb ischemia by a mutant endothelial nitric oxide synthase gene.

    abstract::Gene delivery of angiogenic growth factors is a promising approach for the treatment of ischemic cardiovascular diseases. However, success of this new therapeutic principle is hindered by the lack of critical understanding as to how disease pathology affects the efficiency of gene delivery and/or the downstream signal...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3302781

    authors: Qian HS,Liu P,Huw LY,Orme A,Halks-Miller M,Hill SM,Jin F,Kretschmer P,Blasko E,Cashion L,Szymanski P,Vergona R,Harkins R,Yu J,Sessa WC,Dole WP,Rubanyi GM,Kauser K

    更新日期:2006-09-01 00:00:00

  • Improved titers of HIV-based lentiviral vectors using the SRV-1 constitutive transport element.

    abstract::The development of lentiviral vectors that use Rev-independent mechanisms of nuclear export for their genomic RNA could facilitate the construction of novel anti-HIV vectors. We have improved the titers of Rev-independent lentiviral vectors having the SRV-1 CTE by mutating the major splice donor and acceptor sites pre...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3301262

    authors: Mautino MR,Keiser N,Morgan RA

    更新日期:2000-08-01 00:00:00

  • Efficient tuberculosis treatment in mice using chemotherapy and immunotherapy with the combined DNA vaccine encoding Ag85B, MPT-64 and MPT-83.

    abstract::Although most cases of tuberculosis (TB) can be cured with antibiotics, relapse is common if patients do not continue chemotherapy for at least 6 months. Thus, improved therapeutic strategies are urgently needed. We previously found that the combined DNA vaccine encoding the Mycobacterium tuberculosis proteins Ag85B, ...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/gt.2008.13

    authors: Yu DH,Hu XD,Cai H

    更新日期:2008-05-01 00:00:00

  • Lentivirus-mediated Bcl-2 expression in betaTC-tet cells improves resistance to hypoxia and cytokine-induced apoptosis while preserving in vitro and in vivo control of insulin secretion.

    abstract::betaTC-tet cells are conditionally immortalized pancreatic beta cells which can confer long-term correction of hyperglycemia when transplanted in syngeneic streptozocin diabetic mice. The use of these cells for control of type I diabetes in humans will require their encapsulation and transplantation in non-native site...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3300922

    authors: Dupraz P,Rinsch C,Pralong WF,Rolland E,Zufferey R,Trono D,Thorens B

    更新日期:1999-06-01 00:00:00

  • Gene delivery to rat and human Schwann cells and nerve segments: a comparison of AAV 1-9 and lentiviral vectors.

    abstract::Schwann cells (SCs) in an injured peripheral nerve form pathways for regenerating axons. Although these cells initially support regeneration, SCs lose their pro-regenerative properties following a prolonged period of denervation. Gene transfer to SC can enhance their therapeutic potential. In this article, we compared...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/gt.2015.47

    authors: Hoyng SA,De Winter F,Gnavi S,van Egmond L,Attwell CL,Tannemaat MR,Verhaagen J,Malessy MJ

    更新日期:2015-10-01 00:00:00

  • Retrovirus-mediated gene transfer in lungs of living fetal sheep.

    abstract::In utero somatic gene transfer may be a useful therapeutic strategy for a variety of inherited disorders. In the present study, we demonstrate transgene expression in the airways of fetal lamb lungs, 2-3 weeks after injection of Moloney murine leukemia retrovirus based vectors containing cDNA for beta-galactosidase (l...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:

    authors: Pitt BR,Schwarz MA,Pilewski JM,Nakayama D,Mueller GM,Robbins PD,Watkins SA,Albertine KH,Bland RD

    更新日期:1995-07-01 00:00:00

  • Correction/mutation of acid alpha-D-glucosidase gene by modified single-stranded oligonucleotides: in vitro and in vivo studies.

    abstract::Deficiency in acid alpha-D-glucosidase results in Pompe's disease. Modified single-stranded oligonucleotide (ODN) was designed to correct the acid alpha-D-glucosidase gene with a C1935 --> A (Asp --> Glu) point mutation which causes a complete loss of enzymatic activity for glycogen digestion in the lysosome. The ODN ...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3302096

    authors: Lu IL,Lin CY,Lin SB,Chen ST,Yeh LY,Yang FY,Au LC

    更新日期:2003-10-01 00:00:00

  • Redirecting adenovirus to pulmonary endothelium by cationic liposomes.

    abstract::Somatic gene transfer to the pulmonary endothelium may be a useful strategy for modifying the phenotype of endothelium and/or vascular smooth muscle in disorders such as primary pulmonary hypertension, ARDS or pulmonary metastatic disease. Adenoviral (Ad) vectors, although highly efficient in liver gene transfer, have...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3301636

    authors: Ma Z,Mi Z,Wilson A,Alber S,Robbins PD,Watkins S,Pitt B,Li S

    更新日期:2002-02-01 00:00:00

  • Multi-subtype gp160 DNA immunization induces broadly neutralizing anti-HIV antibodies.

    abstract::A highly desirable feature for an human immunodeficiency virus type 1 (HIV-1) vaccine is the ability to induce broadly reactive anti-envelope antibodies that can neutralize primary HIV-1 isolates. Two immunizations with an HIV-1 envelope-encoding plasmid together with recombinant granulocyte-macrophage colony-stimulat...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3302275

    authors: Rollman E,Hinkula J,Arteaga J,Zuber B,Kjerrström A,Liu M,Wahren B,Ljungberg K

    更新日期:2004-07-01 00:00:00

  • Adeno-associated virus vector enables safe and efficient Cas9 activation in neonatal and adult Cas9 knockin murine cochleae.

    abstract::Adeno-associated virus (AAV)-mediated gene delivery systems have been shown to be effective tools for gene manipulation in the inner ear. For example, hair cells (HCs) and multiple other cell types can be transduced by the local injection of AAVs into the inner ear. However, application of the AAV-mediated CRISPR/Cas9...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/s41434-020-0124-1

    authors: Kang W,Zhao X,Sun Z,Dong T,Jin C,Tong L,Zhu W,Tao Y,Wu H

    更新日期:2020-08-01 00:00:00

  • Human mesenchymal stem cells: from basic biology to clinical applications.

    abstract::Mesenchymal stem cells (MSC) are a group of clonogenic cells present among the bone marrow stroma and capable of multilineage differentiation into mesoderm-type cells such as osteoblasts, adipocytes and chondrocytes. Due to their ease of isolation and their differentiation potential, MSC are being introduced into clin...

    journal_title:Gene therapy

    pub_type: 杂志文章,评审

    doi:10.1038/sj.gt.3303067

    authors: Abdallah BM,Kassem M

    更新日期:2008-01-01 00:00:00

  • Electropermeabilization of skeletal muscle enhances gene transfer in vivo.

    abstract::This work demonstrates that electrical muscle stimulation markedly increases the transfection efficiency of an intramuscular injection of plasmid DNA. In soleus or extensor digitorum longus muscles of adult rats the percentage of transfected fibers increased from about 1 to more than 10. The number of transfected fibe...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3300847

    authors: Mathiesen I

    更新日期:1999-04-01 00:00:00

  • Cell-based osteoprotegerin therapy for debris-induced aseptic prosthetic loosening on a murine model.

    abstract::Exogenous osteoprotegerin (OPG) gene modification appears a therapeutic strategy for osteolytic aseptic loosening. The feasibility and efficacy of a cell-based OPG gene delivery approach were investigated using a murine model of knee prosthesis failure. A titanium pin was implanted into mouse proximal tibia to mimic a...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/gt.2010.64

    authors: Zhang L,Jia TH,Chong AC,Bai L,Yu H,Gong W,Wooley PH,Yang SY

    更新日期:2010-10-01 00:00:00

  • The relevance of coagulation factor X protection of adenoviruses in human sera.

    abstract::Intravenous delivery of adenoviruses is the optimal route for many gene therapy applications. Once in the blood, coagulation factor X (FX) binds to the adenovirus capsid and protects the virion from natural antibody and classical complement-mediated neutralisation in mice. However, to date, no studies have examined th...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/gt.2016.32

    authors: Duffy MR,Doszpoly A,Turner G,Nicklin SA,Baker AH

    更新日期:2016-07-01 00:00:00

  • Targeted gene transfer to corneal endothelium in vivo by electric pulse.

    abstract::A novel method of in vivo targeted gene transfer to intentionally selected areas of the corneal endothelium was developed. Plasmid DNA with the lacZ gene coding for beta-galactosidase was injected into the anterior chamber of adult Wistar rats, and eight pulses of electricity at intensities ranging from 5 to 40 V/cm w...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3300725

    authors: Oshima Y,Sakamoto T,Yamanaka I,Nishi T,Ishibashi T,Inomata H

    更新日期:1998-10-01 00:00:00

  • Tumor-associated antigen/IL-21-transduced dendritic cell vaccines enhance immunity and inhibit immunosuppressive cells in metastatic melanoma.

    abstract::Dendritic cell (DC)-based vaccine approaches are being actively evaluated for developing immunotherapeutic agents against cancers. In this study, we investigated the use of engineered DCs expressing transgenic tumor-associated antigen hgp100 and the regulatory cytokine interleukin-21, namely DC-hgp100/mIL-21, as a the...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/gt.2014.12

    authors: Aravindaram K,Wang PH,Yin SY,Yang NS

    更新日期:2014-05-01 00:00:00

  • Enhanced immune costimulatory activity of primary acute myeloid leukaemia blasts after retrovirus-mediated gene transfer of B7.1.

    abstract::Gene modification of malignant cells to express immune stimulators (cytokines and immune costimulators) has provided the basis for a novel form of immunotherapy. Using a MPSV-based retroviral vector with hygromycin resistance gene as a selectable marker, we have studied retrovirus-mediated gene transfer of an immune c...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3300437

    authors: Hirst WJ,Buggins A,Darling D,Gäken J,Farzaneh F,Mufti GJ

    更新日期:1997-07-01 00:00:00

  • Evidence for localization of biologically active recombinant retroviral vector to lymph nodes in mice injected intramuscularly.

    abstract::We have developed a novel gene transfer drug, HIV-IT(V), for the treatment of HIV infection in humans. HIV-IT(V) is a retroviral vector encoding the HIV-1 IIIB env and rev genes and a neomycin resistance marker gene (neor). We have recently reported that HIV-IT(V) administered intramuscularly to male mice localizes pr...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:

    authors: Kamantigue E,Edwards W 3rd,Chada S,Brumm D,Austin M,Irwin M,Mento S,Kowal K,Sajjadi N

    更新日期:1996-02-01 00:00:00

  • Gene therapy for cystic fibrosis in humans by liposome-mediated DNA transfer: the production of resources and the regulatory process.

    abstract::The number of clinical trials using gene transfer technology, either active or under discussion, is increasing rapidly. However, little information is available describing the regulatory procedures or safety specifications that must be considered before initiation of such trials in Europe. We describe the procedure us...

    journal_title:Gene therapy

    pub_type: 杂志文章,评审

    doi:

    authors: Caplen NJ,Gao X,Hayes P,Elaswarapu R,Fisher G,Kinrade E,Chakera A,Schorr J,Hughes B,Dorin JR

    更新日期:1994-03-01 00:00:00

  • IL-12 plasmid-enhanced DNA vaccination against carcinoembryonic antigen (CEA) studied in immune-gene knockout mice.

    abstract::Intramuscular (i.m.) injection of a plasmid encoding human carcinoembryonic antigen (CEA) elicited immunity against transplanted syngeneic (C57BL/6) CEA-positive Lewis lung carcinoma (CEA/LLC) cells, but tumors still appeared in all mice. In wild-type mice, coinjection of an IL-12 plasmid markedly enhanced anti-CEA hu...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3301274

    authors: Song K,Chang Y,Prud'homme GJ

    更新日期:2000-09-01 00:00:00

  • Discordant effects of a soluble VEGF receptor on wound healing and angiogenesis.

    abstract::Soluble receptors to vascular endothelial growth factor (VEGF) can inhibit its angiogenic effect. Since angiogenesis is involved in wound repair, we hypothesized that adenovirus-mediated gene transfer of a soluble form of VEGF receptor 2 (Flk-1) would attenuate wound healing in mice. C57Bl/6J and genetically diabetic ...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3302162

    authors: Jacobi J,Tam BY,Sundram U,von Degenfeld G,Blau HM,Kuo CJ,Cooke JP

    更新日期:2004-02-01 00:00:00

  • Corticospinal tract transduction: a comparison of seven adeno-associated viral vector serotypes and a non-integrating lentiviral vector.

    abstract::The corticospinal tract (CST) is extensively used as a model system for assessing potential therapies to enhance neuronal regeneration and functional recovery following spinal cord injury (SCI). However, efficient transduction of the CST is challenging and remains to be optimised. Recombinant adeno-associated viral (A...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/gt.2011.71

    authors: Hutson TH,Verhaagen J,Yáñez-Muñoz RJ,Moon LD

    更新日期:2012-01-01 00:00:00