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At least 847 records · Page 47Linked to original sources
PubMed1999

Hepatoma-specific antitumor activity of an albumin enhancer/promoter regulated herpes simplex virus in vivo.

Targeting viral vectors to appropriate cell types so that normal cells are not adversely affected is an important goal for gene therapy. Previously, we described a novel approach to viral gene therapy using a conditional, replication-competent herpes simplex virus (HSV), where replication and associated cytotoxicity are limited to a specific cell-type by the regulated expression of an essential immediate-early viral gene product. In this report we analyze the hepatoma-specific replication, cytotoxicity and anti-tumor effect of recombinant HSV G92A, regulated by the albumin enhancer/promoter. G92A efficiently replicated in vitro in two human hepatoma cell lines expressing albumin, but not in four human non-hepatoma, albumin-non-expressing tumor cell lines, while all cell lines were equally susceptible to a tissue nonspecific HSV recombinant, hrR3. In vivo, G92A replicated well in subcutaneous xenografts of human hepatoma cells (Hep3B) in athymic mice, but not in non-hepatoma subcutaneous tumors (PC3 and HeLa), whereas, hrR3 replicated well in both tumor types. Intratumoral inoculation of G92A inhibited the growth of established subcutaneous hepatoma tumors in nude mice, but not prostate tumors. Replication-competent viral vectors controlled by cell-specific transcriptional regulatory sequences provide a new therapeutic strategy for tumor therapy.

Albumins↗
PubMed2001

Gene therapy for hypertension: sense and antisense strategies.

Gene therapy for hypertension is needed for the next generation of antihypertensive drugs. Current drugs, although effective, have poor compliance, are expensive and short-lasting (hours or one day). Gene therapy offers a way to produce long-lasting antihypertensive effects (weeks, months or years). We are currently using two strategies: antisense oligodeoxynucleotides (AS-ODN), an dantisense DNA delivered in viral vectors, to inhibit genes associated with vasoconstrictive properties. It is not necessary to know all the genes involved in hypertension, since many years of experience with drugs show which genes need to be controlled. AS-ODNs are short, single-stranded DNA that can be injected in naked form or in liposomes. AS-ODNs, targeted to AT1 receptors (AT1R), angiotensinogen (AGT), angiotensin converting enzyme (ACE) and beta 1-adrenergic receptors effectively reduce hypertension in rat models (SHR, 2K-1C and cold-induced) hypertension. The effects can last up to one month when delivered with liposomes. No side effects or toxic effects have been detected and repeated injections can be given. For the vector, adeno-associated virus (AAV) is used with a construct to include a CMV promoter, antisense DNA to AGT or AT1R and a reporter gene. Results in SHR demonstrate reduction and slowing of hypertension development with a single dose administration. Left ventricular hypertrophy is also reduced by AAV-AS-AGT treatment. Double transgenic mice (human renin plus human AGT) with high angiotensin II (Ang II) causing high blood pressure, treated with AAV-AT1R-AS, show a normalisation of blood pressure for over 6 months with a single injection of vector. We conclude that ODNs will probably be developed first because they can be treated like drugs for the treatment of hypertension with long-term effects. Viral vector delivery needs more engineering to be certain of its safety but one day may be used for a very prolonged control of blood pressure.

Angiotensinogen↗
PubMed2000

Somatic gene therapy for hypertension.

Gene therapy for hypertension is needed for the next generation of antihypertensive drugs. Current drugs, although effective, have poor compliance, are expensive and short-lasting (hours or one day). Gene therapy offers a way to produce long-lasting antihypertensive effects (weeks, months or years). We are currently using two strategies: a) antisense oligodeoxynucleotides (AS-ODN) and b) antisense DNA delivered in viral vectors to inhibit genes associated with vasoconstrictive properties. It is not necessary to know all the genes involved in hypertension, since many years of experience with drugs show which genes need to be controlled. AS-ODN are short, single-stranded DNA that can be injected in naked form or in liposomes. AS-ODN, targeted to angiotensin type 1 receptors (AT1-R), angiotensinogen (AGT), angiotensin converting enzyme, and ss1-adrenergic receptors effectively reduce hypertension in rat models (SHR, 2K-1C) and cold-induced hypertension. A single dose is effective up to one month when delivered with liposomes. No side effects or toxic effects have been detected, and repeated injections can be given. For the vector, adeno-associated virus (AAV) is used with a construct to include a CMV promoter, antisense DNA to AGT or AT1-R and a reporter gene. Results in SHR demonstrate reduction and slowing of development of hypertension, with a single dose administration. Left ventricular hypertrophy is also reduced by AAV-AGT-AS treatment. Double transgenic mice (human renin plus human AGT) with high angiotensin II causing high blood pressure, treated with AAV-AT1-R-AS, show a normalization of blood pressure for over six months with a single injection of vector. We conclude that ODNs will probably be developed first because they can be treated like drugs for the treatment of hypertension with long-term effects. Viral vector delivery needs more engineering to be certain of its safety, but one day may be used for a very prolonged control of blood pressure.

Animals↗
PubMed2004

A new gene delivery system based on controlled release technology.

The recent rapid development of molecular biology together with the steady progress of genome projects has given us some essential and revolutionary informations of gene to elucidate all the biological phenomena at the molecular level. Under these circumstances, gene transfection has become a fundamental technology indispensable to the basic research of medicine and biology. On the other hand, the technology of gene transfection is also important for gene therapy of several diseases. Some human gene therapies have been performed with a plasmid DNA alone or virus vectors but are clinically limited by the poor gene expression of plasmid DNA and the adverse effects of virus itself, such as immunogenicity and toxicity or the possible mutagenesis of cells transfected. Therefore, several non-viral vectors of synthetic materials have been explored to enhance the transfection efficiency of gene into mammalian cells both in vitro and in vivo. In this paper, the researches about non-viral vectors and recent research trials about the controlled release of plasmid DNA are briefly reviewed to emphasize the significance of gene delivery technology in basic biology and medicine as well as clinical medicine. A new system of gene release based on biodegradable hydrogel is introduced.

Animals↗
PubMedDate not supplied

In vivo transfection and/or cross-priming of dendritic cells following DNA and adenoviral immunizations for immunotherapy of cancer--changes in peripheral mononuclear subsets and intracellular IL-4 and IFN-gamma lymphokine profile.

In order to provoke an immune response, a tumor vaccine should not only maximize antigen-specific signals, but should also provide the necessary "co-stimulatory" environment. One approach is to genetically manipulate tumor cells to either secrete lymphokines (GM-CSF, IL-12, IL-15) or express membrane bound molecules (CD80, CD86). Furthermore, patient dendritic cells can be loaded with tumor-associated antigens or peptides derived from them and used for immunotherapy. Genetic modification of dendritic cells can also lead to presentation of tumor-associated antigens. Transfection of dendritic cells with DNA encoding for such antigens can be done in vitro, but transfection efficiency has been uniformly low. Alternatively, dendritic cells can also be modulated directly in vivo either by "naked" DNA immunization or by injecting replication-deficient viral vectors that carry the tumor specific DNA. Naked DNA immunization offers several potential advantages over viral mediated transduction. Among these are the inexpensive production and the inherent safety of plasmid vectors, as well as the lack of immune responses against the carrier. The use of viral vectors enhances the immunogenicity of the vaccine due to the adjuvant properties of some of the viral products. Recent studies have suggested that the best strategy for achieving an intense immune response may be priming with naked DNA followed by boosting with a viral vector. We have successfully completed a phase I and phase II clinical trials on immunotherapy of prostate cancer using naked DNA and adenoviral immunizations against the prostate-specific membrane antigen (PSMA) and phase I clinical trial on colorectal cancer using naked DNA immunization against the carcinoembryonic antigen (CEA). The vaccination was tolerated well and no side effects have been observed so far. The therapy has proven to be effective in a number of patients treated solely by immunizations. The success of the treatment clearly depends on the stage of the disease proving to be most efficient in patients with minimal disease or no metastases. A panel of changes in the phenotype of peripheral blood lymphocytes and the expression of intra-T-cell lymphokines seems to correlate with clinical improvement.

Adenoviridae↗
PubMed2003

Novel cGMP liposomal vectors mediate efficient gene transfer.

Viral vector systems are the most commonly used gene transfer tools for clinical gene therapy. However, lipofection systems are potential alternatives because of lower immunogenicity and easier cGMP production, but in vivo stability and transduction efficacy need to be improved. Therefore, we investigated gene transduction efficiency of our novel cGMP cationic lipids, CCQ22 and CCQ32, by FACS analysis. Toxicity analysis was performed to determine the cytotoxic side effects of the novel lipids. To evaluate the stability of the compounds in the context of local delivery to patients with intraperitoneally metastatic ovarian cancer, gene transfer was also tested in the presence of malignant ascites. Our novel cGMP standard lipids mediated gene transfer rates of more than 50%. However, for most cell lines cytotoxic side effects were similar to our reference lipofection system. In general, ascites had no major influence on gene transduction rates with the novel lipids. Our results suggest that CCQs may compare favorably with commercially available lipofection systems. These promising results facilitate further analysis of the compounds.

Ascites↗
PubMed2002

Prolonged maturation and enhanced transduction of dendritic cells migrated from human skin explants after in situ delivery of CD40-targeted adenoviral vectors.

Therapeutic tumor vaccination with viral vectors or naked DNA, carrying the genetic code for tumor-associated Ags, critically depends on the in vivo transduction of dendritic cells (DC). Transfection of predominantly nonprofessional APC and only small numbers of DC may hamper proper T cell activation. Aim of this study was, therefore, the targeted, selective, and enhanced in situ transduction of DC. A human skin explant model was used to explore targeted transduction of cutaneous DC after intradermal injection of a bispecific Ab conjugate to link adenoviral (Ad) vectors directly to CD40 on the DC surface. A significantly enhanced transduction efficiency and selectivity, and an increased activation state of migrating DC were thus achieved. Moreover, DC transduced by CD40-targeted Ad maintained their Ag-specific CTL-stimulatory ability for up to 1 wk after the start of migration, in contrast to DC transduced by untargeted Ad, which had lost this capacity by that time. Because DC targeting in vivo might obviate the need for the in vitro culture of autologous DC for adoptive transfer, CD40-targeted Ad vectors constitute a promising new vaccine modality for tumor immunotherapy.

Adenoviruses, Human↗
PubMed2004

Gene therapy clinical trials worldwide 1989-2004-an overview.

In 1989, Rosenberg et al. performed the first human gene therapy trial when they used a retrovirus to introduce the gene coding for resistance to neomycin into human tumor-infiltrating lymphocytes before infusing them into five patients with advanced melanoma. This study demonstrated the feasibility of using retroviral gene transduction in humans and set the stage for further studies. Since then, over 900 clinical trials have been completed, are ongoing or have been approved worldwide. These trials have been designed to establish feasibility and safety, to demonstrate the reality of expression of therapeutic protein(s) in vivo by the genes transferred and, in some cases, to show therapeutic benefit. There is no single source of information that presents an overview of all the clinical trials undertaken worldwide. In 1997 we set up a database to bring all the information on clinical trials together as comprehensively and as globally as possible. The data were compiled and are regularly updated from official agency sources, the published literature, presentations at conferences and from information kindly provided by investigators or trial sponsors themselves. As of January 31, 2004, we have identified 918 trials in 24 countries. The USA accounts for two-thirds of these trials. Cancer is by far the most common disease indication, followed by inherited monogenic diseases, and cardiovascular diseases. Viral vectors have been the most frequently used vehicles for transferring genes into human cells, with retroviruses and adenoviruses representing the vast majority. Plasmid (naked) DNA and other non-viral vectors have been used in one-quarter of the trials. Over 100 distinct genes have been transferred. This article aims to provide a descriptive overview of the clinical trials that, to the best of our knowledge, have been or are being performed worldwide. Details of the data presented, including an interactive, searchable database that currently holds information on 918 trials, can be found on The Journal of Gene Medicine clinical trials website 1.

Cardiovascular Diseases↗
PubMed2003

Glutathione peroxidase overexpression inhibits cytochrome C release and proapoptotic mediators to protect neurons from experimental stroke.

BACKGROUND AND PURPOSE: Ischemic injury and reperfusion increases superoxide (O2-) production and reduces the ability of neurons to scavenge free radicals, leading to the release of cytochrome c and apoptosis. Here we test whether overexpression with the use of gene therapy of the antioxidant glutathione peroxidase (Gpx), delivered before or after experimental stroke, is protective against ischemic injury. METHODS: Sixty-two rats underwent middle cerebral artery occlusion for 1 hour. Defective herpes simplex viral vectors expressing Gpx/lacZ or lacZ alone (control) were delivered into each striatum 12 hours before or 2 or 5 hours after ischemia onset. RESULTS: Striatal neuron survival at 2 days was improved by 36% when Gpx was delivered 12 hours before ischemia onset, 26% with a 2-hour delay, and 25% when delayed 5 hours. After ischemia, Gpx overexpression significantly reduced cytosolic translocation of cytochrome c and increased the proportion of Bcl-2-positive cells compared with cells transfected with control vector. Bax and activated caspase-3, while present in control-transfected neurons after ischemia, were rarely noted in Gpx-transfected cells. CONCLUSIONS: Expression from these herpes simplex viral vectors begins 4 to 6 hours after injection, which suggests a 9- to 11-hour temporal therapeutic window for Gpx. This is the first study to show that overexpression of Gpx with the use of gene therapy protects against experimental stroke, even with postischemic transfection, and the neuroprotective mechanism involves attenuation of apoptosis-related events.

Animals↗
PubMed2003

The interaction of immunodeficiency viruses with dendritic cells.

Dendritic cells (DCs) can influence HIV-1 and SIV pathogenesis and protective mechanisms at several levels. First, HIV-1 productively infects select populations of DCs in culture, particularly immature DCs derived from blood monocytes and skin (Langerhans cells). However, there exist only a few instances in which HIV-1- or SIV-infected DCs have been identified in vivo in tissue sections. Second, different types of DCs reliably sequester and transmit infectious HIV-1 and SIV in culture, setting up a productive infection in T cells interacting with the DCs. This stimulation of infection in T cells may explain the observation that CD4+ T lymphocytes are the principal cell type observed to be infected with HIV-1 in lymphoid tissues in vivo. DCs express a C-type lectin, DC-SIGN/CD209, that functions to bind HIV-1 (and other infectious agents) and transmit virus to T cells. When transfected into the THP-1 cell line, the cytosolic domain of DC-SIGN is needed for HIV-1 sequestration and transmission. However, DCs lacking DC-SIGN (Langerhans cells) or expressing very low levels of DC-SIGN (rhesus macaque monocyte-derived DCs) may use additional molecules to bind and transmit immunodeficiency viruses to T cells. Third, DCs are efficient antigen-presenting cells for HIV-1 and SIV antigens. Infection with several recombinant viral vectors as well as attenuated virus is followed by antigen presentation to CD4+ and CD8+ T cells. An intriguing pathway that is well developed in DCs is the exogenous pathway for nonreplicating viral antigens to be presented on class I MHC products. This should allow DCs to stimulate CD8+ T cells after uptake of antibody-coated HIV-1 and dying infected T cells. It has been proposed that DCs, in addition to expanding effector helper and killer T cells, induce tolerance through T cell deletion and suppressor T cell formation, but this must be evaluated directly. Fourth, DCs are likely to be valuable in improving vaccine design. Increasing DC uptake of a vaccine, as well as increasing their numbers and maturation, should enhance efficacy. However, DCs can also capture antigens from other cells that are initially transduced with a DNA vaccine or a recombinant viral vector. The interaction of HIV-1 and SIV with DCs is therefore intricate but pertinent to understanding how these viruses disrupt immune function and elicit immune responses.

Animals↗
PubMed2002

Adenoviral-mediated, high-level, cell-specific transgene expression: a SYN1-WPRE cassette mediates increased transgene expression with no loss of neuron specificity.

Viral vectors are excellent tools for studying gene function in the brain, although a limitation has been the ability to effectively target transgene expression to specific neuronal populations. This generally cannot be overcome by the use of neuron-specific promoters, as most are too large to be used with current viral vectors and expression from these promoters is often relatively weak. We therefore developed a composite expression cassette, comprising 495 bp of the weak human SYN1 (synapsin-1) promoter and 800 bp of the woodchuck hepatitis virus posttranscriptional regulatory element (WPRE). Studies in hippocampal cultures, organotypic cultures, and in vivo showed that the 3' addition of the WPRE to the SYN1 element greatly increased enhanced green fluorescent protein expression levels with no loss of neuronal specificity. In vivo studies also showed that transgene expression was enhanced with no loss of neuronal specificity in dentate-gyrus neurons for at least 6 weeks following transfection. Therefore, unlike most powerful promoter systems, which mediate expression in neurons and glia, this SYN1-WPRE cassette can target powerful long-term transgene expression to central nervous system neurons when delivered at relatively low titers of adenovirus. Its use should therefore facilitate both gene therapy studies and investigations of neuronal gene function.

Adenoviridae↗
PubMed1999

Towards molecular farming in the future: transient protein expression in plants.

Molecular farming in plants can be achieved by stable or transient expression of a recombinant protein. Transient expression of recombinant proteins in plants can rapidly provide large amounts of the proteins for detailed characterization. It is fast, flexible and can be carried out at field scale using viral vectors, but it lacks the increases in production volume that can be achieved easily with stable transgenic crops. This review article focuses on discussing the applications of transient expression using viral vectors, biolistic methods or agroinfiltration.

Antibodies↗
PubMed2003

[Gene transfer systems and gene therapy].

One of the most important developments in medicine is gene therapy. But before it can be accepted to be used widely, certain technical problems should be overcome, especially the methods of gene delivery. In order to modify a specific cell type or tissue, the therapeutic gene must be efficiently delivered to the cell, in such a way that the gene can be expressed at the appropriate level and for a sufficient duration. There are currently availible two gene delivery vehicles. The first consists of viral vectors, which take advantage of a variety of naturally occurring viruses to shuttle the foreign cargo to be integrated permanently into the host's chromosome. The second is non-viral vectors, which rely on direct delivery of either naked DNA or mixture of genes with cationic lipids (liposome). There have been over 600 clinical trials of gene therapy protocols. The majority of clinical trials of gene therapy have been involved in the treatment of cancer and most of them have been at phase I clinical trials. Phase II stage of gene therapy had started of the end of 1996.

Clinical Trials as Topic↗
PubMed1998

Expression of adeno-associated virus integrated transgene within the mammalian vestibular organs.

HYPOTHESIS: Adeno-associated virus (AAV) is a suitable viral vector for transgene expression within the mammalian vestibular organs. BACKGROUND: In vivo introduction and expression of a foreign gene within the cochlear tissues have been established using a variety of viral vectors and guinea pig as the animal model. However, the vestibular neuroepithelia of the mammalian inner ear as a potential target for transgene expression remain to be investigated. METHODS: Transgene expression was assessed within the vestibular neuroepithelia of guinea pigs after intracochlear infusion of the recombinant AAV vector with the aid of an osmotic minipump. Evaluation of the transgene within the vestibular apparatus focused on its duration of expression from 2-24 weeks after intracochlear AAV infusion using immunohistochemistry. RESULTS: In the AAV-beta-galactosidase (beta-gal)-infused animals, the sensory hair cells as well as the supporting epithelial cells of cristae and maculae were positive for the transgene expression. The relative level of beta-gal expression was noted to decrease progressively over time. Transduction of the vestibular neuroepithelia also was observed in the contralateral ear, a finding that has been documented previously in AAV-integrated transgene expression in the cochlea. CONCLUSION: This study reports the first demonstration of introduction and long-term transgene expression within the vestibular neuroepithelia. The ability to express a foreign gene with the vestibular system allows the possibility of experimental and therapeutic application of gene therapy technology to address vestibular function and dysfunction.

Animals↗
PubMed2004

A recombinant adenoviral vector encoding functional vasoactive intestinal peptide.

Vasoactive intestinal peptide (VIP) is a small neuropeptide, which exerts pleiotropic functions. Based on its immunomodulatory, secretory, and possibly trophic effects, VIP is a valuable candidate molecule for the management of autoimmune disease. The purpose of this study was to develop a recombinant viral vector capable of directing the expression of functional VIP. The vector rAd5CMVhVIP was constructed and used to infect 293 cells. VIP expression was measured by an ELISA and function was evaluated by measurement of intracellular cAMP formation. rAd5CMVhVIP directed VIP expression and the transgenic VIP elicited a dose-dependent increase of intracellular cAMP, mediated through the VIP receptor VPAC(1). This is the first report showing the construction of a recombinant viral vector encoding biologically active VIP.

Adenoviridae↗
PubMed2006

Delivery of large genomic DNA inserts >100 kb using HSV-1 amplicons.

The principal aim of gene therapy for recessive genetic diseases is to supplement the loss of function of an endogenous gene. For the treatment of many diseases regulation of transgene expression at physiological levels, expression of multiple splice variants, and correct tissue specificity are of utmost importance for effective therapy. We therefore believe the use of a complete genomic locus, in which the native promoter and regulatory regions drive and control expression, is an elegant and effective alternative to traditional complementary DNA (cDNA) vectors utilising heterologous promoters. Viral vectors have proved, over the years, to be an effective means of gene delivery in vitro and in vivo, but the size of complete genomic loci precludes their use in most viral systems. One notable exception comprises the amplicon-type vectors based on human herpesviruses, such as the herpes simplex virus type I (HSV-1) amplicon vector. The large genome of HSV-1 (152 kb) confers upon HSV-1 amplicons a very large transgene capacity sufficient to accommodate approximately 95% of human genomic loci. The combination of the large transgene capacity, a broad range of cell tropism, and the ability to infect dividing and non-dividing cells makes HSV-1 amplicons an excellent vector system to develop for the delivery of large genomic loci. Here we review recent work which has shown that HSV-1 amplicons can be used for the delivery and expression of large genomic inserts >100 kb to cells in culture to rescue phenotypes in cellular models of genetic disease. We then discuss applications for high capacity HSV-1 amplicons in vivo and their potential to facilitate the use of large genomic inserts in gene therapy treatment regimes.

DNA↗
PubMed2004

Neuronal expression and regulation of CGRP promoter activity following viral gene transfer into cultured trigeminal ganglia neurons.

We have examined the regulation of calcitonin gene-related peptide (CGRP) promoter activity in primary cultures of rat trigeminal ganglia neurons. A viral vector was used to circumvent the potential complication of examining only a small subpopulation of cells in the heterogeneous cultures. Infection with high titers of recombinant adenovirus containing 1.25 kb of the rat CGRP promoter linked to the beta-galactosidase reporter gene (AdCGRP-lacZ) yielded expression in about 50% of the CGRP-expressing neurons. The CGRP-lacZ reporter gene was preferentially expressed in neurons, with 91% co-expression with endogenous CGRP. In contrast, an adenoviral vector containing a CMV-lacZ reporter was predominantly expressed in non-neuronal cells, with only 29% co-expression with CGRP. We then asked whether the CGRP promoter in the viral vector could be regulated by serotonin receptor type 1 (5-HT(1)) agonists. Promoter activity was decreased two- to threefold by treatment with five 5-HT(1B/D) agonists, including the triptan drugs sumatriptan, eletriptan, and rizatriptan that are used for migraine treatment. As controls, CMV promoter activity was not affected, and 5-HT(1B/D) receptor antagonists blocked the repression caused by sumatriptan and eletriptan. Thus, adenoviral gene transfer can be used in trigeminal ganglia neurons for studying the mechanisms of triptan drug action on CGRP synthesis.

Adenoviridae↗
PubMed2000

Adenovirus-mediated gene therapy to liver grafts: successful gene transfer by donor pretreatment.

BACKGROUND: We have previously shown excellent adenoviral (Ad) gene transfection to transplanted liver grafts with the clamp technique (CT) where viral vector was delivered ex vivo and trapped in cold preserved liver grafts. In this study, we adopted a new gene therapy approach to achieve early transgene expression by donor pretreatment with viral vector and compared the efficacy of these two methods by using Ad vector encoding enhanced green fluorescent protein (AdEGFP) marker gene. METHODS: AdEGFP (1 x 10(9)plaque forming units) was delivered to the liver grafts by: (1) single intravenous injection to donor Lewis rats 48 hours before harvesting, (2) ex vivo cold infusion into the harvested liver with CT, or (3) a combination of both methods. Liver grafts were stored in University of Wisconsin solution at 4 degrees C for 18 hours and then orthotopically transplanted into syngeneic recipients, and the expression of EGFP was studied. RESULTS: With intravenous pretreatment of donor liver grafts, EGFP-expressing cells were detected as early as 3 hours after transplant, and moderate expression was seen by 12 hours. In contrast, EGFP was not detected until 12 to 24 hours after transplant with CT. High levels of EGFP-producing cells were seen with each technique at 7 days ( approximately 30% transfection efficiency). A combination of both methods did not enhance infectivity. Liver preservation injury was comparable between groups. CONCLUSIONS: Gene transfer by donor pretreatment with AdEGFP induces early and efficient gene transduction to liver grafts compared with back-table delivery with CT. This method is simple and provides early transgene expression in liver grafts that potentially could be used to deliver genes to decrease preservation injury or rejection.

Adenosine↗