Localized adenovirus gene delivery using antiviral IgG complexation.

Abstract:

:Gene therapy with viral vectors has progressed to clinical trials. However, the localization of viral vector delivery to diseased target sites remains a challenge. We tested the hypothesis that an adenoviral vector could be successfully delivered by complexation with a specific antibody that is bound to a biodegradable matrix designed for achieving localized gene transduction. We report the first successful delivery system based upon antibody immobilization of virions in a type I collagen-avidin gel using a polyclonal biotinylated IgG specific for the adenovirus hexon. In vitro stability studies demonstrated retention of viral vector activity with antibody-complexed adenovirus collagen gel preparations, in comparison to loss of vector activity from collagen gels prepared with nonspecific biotinylated IgG. Cell culture investigations using this antibody-controlled release system for adenoviral vector transduction of rat aortic smooth muscle cells (A10) demonstrated a significantly more localized reporter expression (beta-galactosidase) compared with non-antibody-complexed controls. Herpes simplex thymidine kinase (HSVtk) adenoviral vectors were immobilized on avidin-collagen gels via this antibody-complexation approach, and ganciclovir was added to rat smooth muscle cells (A10) in culture with the gels. With complexed HSVtk adenovirus, only cells either in contact with the virus-containing gel or within 50 microm were killed. By comparison, at the same adenovirus and ganciclovir dose, non-antibody-complexed HSVtk adenoviral delivery with ganciclovir resulted in the death of virtually all cells. Myocardial gene transfer studies in pigs demonstrated significantly more efficient right ventricular adenoviral GFP expression with anti-hexon antibody-complexed matrix injections, compared with direct vector injections. Thus, our results show that matrix formulations based on antibody-complexation delivery of adenovirus resulted in site-specific localization of transgene expression that enhances the efficiency of therapeutic vector strategies and provides a potent means for localization, to avoid distal side-effects. This approach has therapeutic potential as an implantable preparation that through the means of antibody-complexation, can localize and optimize viral vector gene therapy.

journal_name

Gene Ther

journal_title

Gene therapy

authors

Levy RJ,Song C,Tallapragada S,DeFelice S,Hinson JT,Vyavahare N,Connolly J,Ryan K,Li Q

doi

10.1038/sj.gt.3301452

keywords:

subject

Has Abstract

pub_date

2001-05-01 00:00:00

pages

659-67

issue

9

eissn

0969-7128

issn

1476-5462

journal_volume

8

pub_type

杂志文章
  • Adenoviral vectors for in vivo gene delivery to oligodendrocytes: transgene expression and cytopathic consequences.

    abstract::Replication defective viral vectors provide a potentially useful means of gene transfer to oligodendrocytes and thus for studying the pathogenesis of white matter disease. In this study we have examined the expression pattern of E1/E3 deleted adenoviral vectors expressing the reporter gene LacZ (AdlacZ) as a means of ...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3300971

    authors: Franklin Rm,Quick Mm,Haase G

    更新日期:1999-08-01 00:00:00

  • Successful target cell transduction of capsid-engineered rAAV vectors requires clathrin-dependent endocytosis.

    abstract::Cell surface targeting of recombinant adeno-associated virus (rAAV) vectors is an attractive strategy to modify AAV's natural tropism. As modification of the capsid surface is likely to affect the mechanism of vector internalization and consequently the vector's intracellular fate, we investigated early steps in cell ...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/gt.2011.78

    authors: Uhrig S,Coutelle O,Wiehe T,Perabo L,Hallek M,Büning H

    更新日期:2012-02-01 00:00:00

  • Human urinary bladder carcinomas express adenovirus attachment and internalization receptors.

    abstract::The use of adenoviral vectors as potent gene delivery systems requires expression of the Coxsackievirus/adenovirus receptor (CVADR) on the target cell surface. This receptor is important for virus attachment to the cell surface. For effective internalization of the vector into the target cell the integrins alpha(v)bet...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3301689

    authors: Loskog A,Hedlund T,Wester K,de la Torre M,Philipson L,Malmström PU,Tötterman TH

    更新日期:2002-05-01 00:00:00

  • Expression and activity of human Na+/I- symporter in human glioma cells by adenovirus-mediated gene delivery.

    abstract::Radioiodide concentrating activity in the thyroid, mediated by human Na+/I- symporter (hNIS), provides a mechanism for effective radioiodide treatment for patients who have invasive, recurrent, and metastatic thyroid cancers after total thyroidectomy. In an attempt to develop hNIS gene transfer for radioiodide therapy...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3301170

    authors: Cho JY,Xing S,Liu X,Buckwalter TL,Hwa L,Sferra TJ,Chiu IM,Jhiang SM

    更新日期:2000-05-01 00:00:00

  • Progress and prospects: gene therapy for mitochondrial DNA disease.

    abstract::Defects of the mitochondrial genome cause a wide variety of clinical disorders. Except for rare cases where surgery or transplant is indicated, there is no effective treatment for patients. Genetic-based therapies are consequently being considered. On account of the difficulties associated with mitochondrial (mt) tran...

    journal_title:Gene therapy

    pub_type: 杂志文章,评审

    doi:10.1038/gt.2008.91

    authors: Kyriakouli DS,Boesch P,Taylor RW,Lightowlers RN

    更新日期:2008-07-01 00:00:00

  • Functional correction of T cells derived from patients with the Wiskott-Aldrich syndrome (WAS) by transduction with an oncoretroviral vector encoding the WAS protein.

    abstract::T-cell dysfunction is thought to be central to the immunodeficiency state seen in patients with the Wiskott-Aldrich syndrome (WAS). Aspects of the WAS phenotype have been corrected in other cell types on introduction of the normal WAS protein (WASP), but the potential for correction of the T-cell defects has not been ...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3301950

    authors: Strom TS,Gabbard W,Kelly PF,Cunningham JM,Nienhuis AW

    更新日期:2003-05-01 00:00:00

  • Enhanced in vivo adenovirus-mediated gene transfer to rat hepatocarcinomas by selective administration into the hepatic artery.

    abstract::Adenovirus-mediated gene therapy of experimental hepatocarcinoma is hindered by low transduction efficacy in vivo. We evaluated the extent of gene expression following various routes of administration of recombinant adenovirus AdCMVlacZ in diethylnitrosamine-induced rat hepatocarcinoma. We first characterized the vasc...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3300664

    authors: Gérolami R,Cardoso J,Bralet MP,Cuenod CA,Clément O,Tran PL,Bréchot C

    更新日期:1998-07-01 00:00:00

  • Therapeutic effect of prenatal alkalization and PTC124 in Na(+)/HCO3(-) cotransporter 1 p.W516* knock-in mice.

    abstract::We created Na(+)/HCO3(-) cotransporter 1 (NBCe1) p.W516* knock-in mice as a model of isolated proximal renal tubular acidosis showing early lethality associated with severe metabolic acidosis to investigate the therapeutic effects of prenatal alkalization or posttranscriptional control 124 (PTC124). NBCe1(W516*/W516*)...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/gt.2015.7

    authors: Fang YW,Yang SS,Chau T,Nakamura M,Yamazaki O,Seki G,Yamada H,Hsu HM,Cheng CJ,Lin SH

    更新日期:2015-05-01 00:00:00

  • T cell activation with systemic agonistic antibody versus local 4-1BB ligand gene delivery combined with interleukin-12 eradicate liver metastases of breast cancer.

    abstract::We have shown that interleukin-12 (IL-12) generated a strong, albeit transient, anti-tumor response, mostly mediated by natural killer (NK) cell. T cell participation, in addition to NK cells, was essential for persistence of the anti-tumor response. Ligation of 4-1BB, a co-stimulatory receptor expressed on activated ...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3301687

    authors: Martinet O,Divino CM,Zang Y,Gan Y,Mandeli J,Thung S,Pan PY,Chen SH

    更新日期:2002-06-01 00:00:00

  • Gene transfer into human hematopoietic progenitor cells with an episomal vector carrying an S/MAR element.

    abstract::Episomally maintained self-replicating systems present attractive alternative vehicles for gene therapy applications. Recent insights into the ability of chromosomal scaffold/matrix attachment regions (S/MARs) to mediate episomal maintenance of genetic elements allowed the development of a small circular episomal vect...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3302593

    authors: Papapetrou EP,Ziros PG,Micheva ID,Zoumbos NC,Athanassiadou A

    更新日期:2006-01-01 00:00:00

  • 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

  • Oxytocin neurones in the supraoptic nucleus (SON) are inhibited by endogenous opioids in late pregnant rats.

    abstract::Late pregnant rats exhibit endogenous opioid restraint of oxytocin cells since i.v. naloxone (NLX opioid antagonist) increases oxytocin (OXT) secretion but OXT nerve terminals become desensitised to opioids. We have studied central opioid inhibition of OXT neurones in late pregnancy by measuring SON OXT neurones firin...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:

    authors: Douglas AJ,Johnstone LE,Neumann I,Leng G,Russell JA

    更新日期:1994-01-01 00:00:00

  • Enhanced transduction of mouse salivary glands with AAV5-based vectors.

    abstract::We previously demonstrated that recombinant adeno-associated virus vectors based on serotype 2 (rAAV2) can direct transgene expression in salivary gland cells in vitro and in vivo. However, it is not known how other rAAV serotypes perform when infused into salivary glands. The capsids of serotypes 4 and 5 are distinct...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3302691

    authors: Katano H,Kok MR,Cotrim AP,Yamano S,Schmidt M,Afione S,Baum BJ,Chiorini JA

    更新日期:2006-04-01 00:00:00

  • Technical requirements for effective regional hydrodynamic gene delivery to the left lateral lobe of the rat liver.

    abstract::Hydrodynamic gene delivery to the liver is an attractive approach for clinical liver gene therapy, but critical aspects of technique remain uncertain. There has not been to date any report of high levels of hydrodynamic gene delivery to the liver, except in rodents. Regional hydrodynamic delivery to individual lobes/s...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/gt.2009.167

    authors: Sawyer GJ,Zhang X,Fabre JW

    更新日期:2010-04-01 00:00:00

  • A dual chain chimeric antigen receptor (CAR) in the native antibody format for targeting immune cells towards cancer cells without the need of an scFv.

    abstract::Adoptive cell therapy with chimeric antigen receptor (CAR)-modified T cells showed remarkable therapeutic efficacy in the treatment of leukaemia/lymphoma. However, the application to a variety of cancer entities is often constricted by the non-availability of a single chain antibody (scFv), which is usually the target...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/gt.2016.48

    authors: Faitschuk E,Nagy V,Hombach AA,Abken H

    更新日期:2016-10-01 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

  • Tetracycline-inducible transgene expression mediated by a single AAV vector.

    abstract::Regulated gene delivery systems are usually made of two elements: an inducible promoter and a transactivator. In order to optimize gene delivery and regulation, a single viral vector ensuring adequate stoichiometry of the two elements is required. However, efficient regulation is hampered by interferences between the ...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3301838

    authors: Chtarto A,Bender HU,Hanemann CO,Kemp T,Lehtonen E,Levivier M,Brotchi J,Velu T,Tenenbaum L

    更新日期:2003-01-01 00:00:00

  • HSV vector-mediated transduction and GDNF secretion from adipose cells.

    abstract::The accessibility of adipose tissue and its ability to secrete various bioactive molecules suggest that adipose cells may be attractive targets for gene therapy applications. Here, we report the use of highly defective herpes simplex virus (HSV) vectors as suitable gene transfer agents for adipose cells in culture and...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3302359

    authors: Fradette J,Wolfe D,Goins WF,Huang S,Flanigan RM,Glorioso JC

    更新日期:2005-01-01 00:00:00

  • Folate receptor mediated DNA delivery into tumor cells: potosomal disruption results in enhanced gene expression.

    abstract::We have used a particular folate receptor, which is overexpressed in tumor cells, for targeted DNA delivery into these cell types. This folate receptor internalizes folate through caveolae by a process named potocytosis, which is distinct from endocytosis, through clathrin-coated pits. When folate conjugated to poly-L...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:

    authors: Gottschalk S,Cristiano RJ,Smith LC,Woo SL

    更新日期:1994-05-01 00:00:00

  • Bicistronic transfer of CDKN2A and p53 culminates in collaborative killing of human lung cancer cells in vitro and in vivo.

    abstract::Cancer therapies that target a single protein or pathway may be limited by their specificity, thus missing key players that control cellular proliferation and contributing to the failure of the treatment. We propose that approaches to cancer therapy that hit multiple targets would limit the chances of escape. To this ...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/s41434-019-0096-1

    authors: Xande JG,Dias AP,Tamura RE,Cruz MC,Brito B,Ferreira RA,Strauss BE,Costanzi-Strauss E

    更新日期:2020-02-01 00:00:00

  • Robust cardiomyocyte-specific gene expression following systemic injection of AAV: in vivo gene delivery follows a Poisson distribution.

    abstract::Newly isolated serotypes of AAV readily cross the endothelial barrier to provide efficient transgene delivery throughout the body. However, tissue-specific expression is preferred in most experimental studies and gene therapy protocols. Previous efforts to restrict gene expression to the myocardium often relied on dir...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/gt.2010.105

    authors: Prasad KM,Xu Y,Yang Z,Acton ST,French BA

    更新日期:2011-01-01 00:00:00

  • scAAV-mediated gene transfer of interleukin-1-receptor antagonist to synovium and articular cartilage in large mammalian joints.

    abstract::With the long-term goal of developing a gene-based treatment for osteoarthritis (OA), we performed studies to evaluate the equine joint as a model for adeno-associated virus (AAV)-mediated gene transfer to large, weight-bearing human joints. A self-complementary AAV2 vector containing the coding regions for human inte...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/gt.2012.81

    authors: Watson RS,Broome TA,Levings PP,Rice BL,Kay JD,Smith AD,Gouze E,Gouze JN,Dacanay EA,Hauswirth WW,Nickerson DM,Dark MJ,Colahan PT,Ghivizzani SC

    更新日期:2013-06-01 00:00:00

  • Cultured human myoblasts and myotubes show markedly different transducibility by replication-defective adenovirus recombinants.

    abstract::Human adenovirus (AV) is a favored vector for delivery of therapeutic genes into certain target cells, such as skeletal muscle cells for gene therapy. Here we show that replication-defective (E1 + E3 deleted) human type 5 adenovirus (AV) recombinants containing a reporter gene insert (RSV-luciferase or RSV-Lux) can ve...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:

    authors: Acsadi G,Jani A,Huard J,Blaschuk K,Massie B,Holland P,Lochmüller H,Karpati G

    更新日期:1994-09-01 00:00:00

  • Osteogenic potential of five different recombinant human bone morphogenetic protein adenoviral vectors in the rat.

    abstract::Bone morphogenetic protein (BMP) adenoviral vectors for the induction of osteogenesis are being developed for the treatment of bone pathology. However, it is still unknown which BMP adenoviral vector has the highest potential to stimulate bone formation in vivo. In this study, the osteogenic activities of recombinant ...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3302075

    authors: Li JZ,Li H,Sasaki T,Holman D,Beres B,Dumont RJ,Pittman DD,Hankins GR,Helm GA

    更新日期:2003-09-01 00:00:00

  • A strict-late viral promoter is a strong tumor-specific promoter in the context of an oncolytic herpes simplex virus.

    abstract::Confinement of transgene expression to target cells is highly desirable in gene therapy. Current strategies of transcriptional targeting to tumors usually rely on tissue-specific promoters to control gene expression. However, such promoters generally have much lower activity than the constitutive viral promoters. We h...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3302029

    authors: Fu X,Meng F,Tao L,Jin A,Zhang X

    更新日期:2003-08-01 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

  • Clinical retroviral vector production: step filtration using clinically approved filters improves titers.

    abstract::Production of retroviral vectors for clinical use requires removal of cells and cellular debris. We combined a series of filters of decreasing pore size using commercially available blood banking filters approved for clinical use. The collection bag and filters can be connected to create a sterile, closed system using...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3301328

    authors: Reeves L,Cornetta K

    更新日期:2000-12-01 00:00:00

  • Incorporation of beta-globin untranslated regions into a Sindbis virus vector for augmentation of heterologous mRNA expression.

    abstract::Polynucleotide immunization has been employed as a means of inducing immune responses through the introduction of antigen-encoding DNA. While immunization against specific tumor antigens may be achieved through this strategy, various candidate tumor antigens may not be approached via DNA-based vaccines as they represe...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3300423

    authors: Strong TV,Hampton TA,Louro I,Bilbao G,Conry RM,Curiel DT

    更新日期:1997-06-01 00:00:00

  • RNA knockdown as a potential therapeutic strategy in Parkinson's disease.

    abstract::Parkinson's disease is a prevalent progressive degenerative disorder of the elderly. There is a current need for novel therapeutic strategies because the standard levodopa pharmacotherapy is only temporarily efficacious. Recently, there have been some high-profile successful preclinical results obtained in animal mode...

    journal_title:Gene therapy

    pub_type: 杂志文章,评审

    doi:10.1038/sj.gt.3302669

    authors: Manfredsson FP,Lewin AS,Mandel RJ

    更新日期:2006-03-01 00:00:00

  • Genetic co-inactivation of macrophage- and T-tropic HIV-1 chemokine coreceptors CCR-5 and CXCR-4 by intrakines.

    abstract::CC-chemokine receptor (CCR)-5 is the principal coreceptor for the entry of macrophage (M)-tropic HIV-1 viruses into a cell, while CXC-chemokine receptor (CXCR)-4 is the principal coreceptor for T cell line (T)-tropic HIV-1. In this study, we utilized a novel intracellular chemokine (intrakine) strategy to co-inactivat...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3300667

    authors: Bai X,Chen JD,Yang AG,Torti F,Chen SY

    更新日期:1998-07-01 00:00:00