Adenovirus mediated transfer of the cftr gene to lung of nonhuman primates. Pdf article adenovirusmediated p53 gene transfer in. Much less information is available concerning adenovirus mediated gene transfer to sensory neurons. N2 the introduction of foreign genetic material into somatic cells in intact organisms is an important investigational technique that holds considerable promise as a therapeutic tool. We investigated the use of a new gene therapy in patients with the disorder. Lechman er, jaffurs d, glorioso jc, evans ch, robbins pd. Adenovirusmediated gene transfer to the peritoneum and hepatic parenchyma of fetal mice in utero surgery, vol. Adenovirus mediated gene transfer of insulinlike growth factor 1 stimulates proteoglycan synthesis in rabbit joints. Much work has demonstrated the potential benefits and limitations of adenovirus mediated gene therapy preclinically and clinically, the. Although successful gene transfer has been achieved by the use of both cell mediated and direct techniques, most strategies have been limited either by. These metrics are regularly updated to reflect usage leading up to the last few days. Genetic modification of dc is under study for cancer immunotherapy, vaccine development, and antigentargeted immunosuppression. Cancer gene therapy by adenovirusmediated gene transfer volume. Nih intends to grant the selected licensees a worldwide royaltybearing licenses to practice the inventions embodied in u.
In conclusion, adenovirusmediated gene transfer to nonhuman primate livers via the portal vein or saphenous vein is efficient, but it results in transient expression and is accompanied by an. At present, gene transfer mediated by an adenovirusassociated virus aav vector shows the greatest promise for longterm correction of hemophilia b in the preclinical setting. Adenoviral bcl2 and ischemic renal failure enzyme and preparation or. Methods we infused a single dose of a serotype8pseudotyped, selfcomplementary adenovirusassociated virus. Original article from the new england journal of medicine adenovirus associated virus vectormediated gene transfer in hemophilia b. The use of adenoviral vectors for gene therapy and gene. Inactivation of e2a in recombinant adenoviruses improves the prospect for gene therapy in cystic fibrosis.
Abstractthreedimensional organoids have been recently established from various tissuespecific progenitors such as. Adenovirus mediated efficient gene transfer intoculturedthreedimensionalorganoids pone. Adenovirusmediated gene transfer to treat neurologic disease. We investigated the use of a new gene therapy in patients with the. We have found that although mscs can be infected in vitro by adenoviruses, high virus titers are needed to achieve high efficiency. Adenovirusmediated bcl2 gene transfer inhibits renal. Pdf hemophilia b, an xlinked disorder, is ideally suited for gene therapy. Various versatile vector systems have been developed which can be used for the reliable production of recombinant adenoviruses. Adenovirusassociated virus vector mediated gene transfer. The majority of studies of adenovirus mediated gene transfer to the nervous system have involved neurons within or derived from the central nervous system 1, 4, 12, 16, 27, 29, 35, 38, 42and sympathetic neurons in culture 29, 41. Anionic liposomes increase the efficiency of adenovirus mediated gene transfer to coxsackie adenovirus receptor deficient cells. Similarly, when adenoviral vectors expressing either human factor viii or factor ix adenovirus gene therapy and gene transfer in vivo bramson, graham and gauldie 593 are administered to mice via i.
Cell cycle dependence of gene transfer by lipoplex. Recombinant adenoviral vector, long term gene transfer, newborn mouse, heart, cardiomyocytes. Adenovirusmediated gene transfer to retinal ganglion cells. In designing the retrovirus vector, the rationale for choosing momlvbased vector and the rsv internal promoter, and introducing wpre 28sequence fig. As an alternative approach to gene transfer in lymphocytes, we sought to develop methods to allow the introduction of genes by using adenovirus vectors. Injection of an adenovirus vector into the superior colliculus is an effective means to transfer and express a gene in retinal ganglion cells while avoiding damage to. Phase i study of a recombinant adenovirusmediated gene transfer in lung cancer patients. The results of this study demonstrate the potential for gene therapy by adenovirus. Qiaohua wu, terence moyana and jim xiang affiliation. Adenovirusmediated efficient gene transfer into cultured. Adenovirusmediated gene transfer to cultured nodose. We explored the feasibility of intravenous adenovirusmediated gene therapy to address visceral storage in mps vii. To evaluate the capacity of a replicationdefective adenoviral vector to transport retrogradely from the superior colliculus to the nuclei of retinal ganglion cells and to express in these cells vectorencoded transgene.
At present, gene transfer mediated by an adenovirus associated virus aav vector shows the greatest promise for longterm correction of hemophilia b in the preclinical setting. The research unit, healthresearch division, saskatchewan cancer agency, 20 campus drive,saskatoon, saskatchewan s7n 4h4, canada keywords. Abstract background hemophilia b, an xlinked disorder, is ideally suited for gene therapy. Adverse effects of adenovirusmediated gene transfer of. Results characteristics of the study participants six men with severe hemophilia b fix activity, adenovirusmediated gene transfer robert d. Meidell the introduction of foreign genetic material into somatic cells in intact organisms is an important investigational technique that holds considerable promise as a therapeutic tool. In the future, adenovirus and other gene transfer systems will greatly augment our ability to cure diseases by allowing clinicians to transfer specific genes to increase neuronal survival, help repair traumatic brain injury, destroy tumors, or replace defective genes.
High efficiency adenovirusmediated gene transfer to human. Histological analysis indicated that the new ossicles that developed in the thigh muscles of the mice had different osseous components including bone trabeculae, bone marrow, and chondrified tissue. However, targeting of liver cells by adenoviruses compromises their potential efficacy. Methods preparation of recombinant adenovirus the recombinant cftr adenovirus ad. Efficient and selective adenovirusmediated gene transfer into. Adenovirus serotype 5 hexon mediates liver gene transfer. We infused a single dose of a serotype8pseudotyped, selfcomplementary adenovirusassociated virus aav. Dendritic cells dcs are essential for initiating and directing antigenspecific tcell responses. Adenovirusmediated gene transfer university of texas. Amelioration of collageninduced arthritis in rats by. Adenoviral gene therapy in liver transplantation has many potential applications, but current vector delivery methods to grafts lack efficiency and require high titers.
Adenovirus ad type 5 ad5 mediated gene transfer to mouse bone marrow dcs and human monocytederived dcs is inefficient because neither express the cognate high. Adenoviruses are common pathogens used experimentally and in completed and ongoing clinical trials for gene delivery in oncology, cardioangiology, and regenerative medicine and as vaccine vectors schenkbraat et al. Adenovirusassociated virus vectormediated gene transfer. A simple technique to establish a longterm adenovirus. Gene therapy involves the introduction of genetic material into cells to replace or supplement defective genes or to induce the expression of a novel gene to help. Adenovirusmediated gene transfer to retinal ganglion cells iovs. Previous studies using different techniques have shown that adenoviral mediated gene transfer to different tissues, including the kidney, is more efficient in neonatal mice. Recombinant adenoviruses are attractive vectors for shortterm expression in mouse liver and primary cell lines. Adenovirusmediated gene transfer into monocytederived. Adenoviruses are used extensively as gene transfer agents, both experimentally and clinically. Get a printable copy pdf file of the complete article 3. Adenovirus mediated in vivo gene transfer and expression in normal rat liver.
Wilson abstract in preparation for hunian trials of gene therapy for cystic fibrosis cf, we performed a preclinical study of. Adenovirusmediated gene transfer and expression of human. Adenoviralmediated gene transfer to rabbit synovium in vivo. In cell culture, the adenovirus serotype 5 fiber protein engages the coxsackievirus and adenovirus receptor car to bind cells. Adenovirus mediated p53 gene transfer in advanced nonsmallcell lung cancer stephen g. Patent 6,0,638 entitled adenovirus comprising deletions on the e1a, e1b and e3 regions for transfer of genes to the lung u. Adenovirusmediated transfer of the cftr gene to lung of nonhuman primates.
The fascinating concept of suicide gene therapy also. In this study, a replicationdefective adenovirus vector mediated gene transfer was used to augment bcl2 in rat kidney to obviate concerns regarding the purity of the 1194. Pdf influence of temperature on adenovirusmediated gene. Adenovirus mediated gene transfer into monocytederived macrophages of patients with xlinked chronic granulomatous disease. Pdf phase i study of a recombinant adenovirusmediated.
In comparison to transfection efficiency of the homologous expression plasmid, adenovirus mediated gene transfer was substantially more efficient. Here, we investigate if the commonlyused cationic polymer polybrene can potentiate adenovirus mediated transgene delivery into mscs, such as c2c12. Adenovirus ad vectors are promising for gene therapy of glioma due to their ability to achieve efficient gene transfer upon intratumoral administration. These issues include the choice of gene delivery system, the need for extensive preclinical testing to ensure the feasibility and safety of the approach, and careful monitoring of subjects for short and longterm toxicity associated with the genetransfer protocol. Patent application sn 09364,839 entitled adenovirus mediated transfer of. Adenovirusmediated gene transfer into human hepatocytes nature. Anionic liposomes increase the efficiency of adenovirus. Feasibility of adenovirus mediated hnis gene transfer and 1i radioiodine therapy as a definitive treatment for localized prostate cancer kenneth n barton1, hans stricker2, mohamed a elshaikh 1, jan pegg, jingfang cheng 1, yingshu zhang, kastytis c karvelis3, mei. Adenovirus mediated delivery of human cd39 gene during coronary perfusion and cold preservation resulted in efficient albeit delayed expression of cd39, within both ec and endocardium in addition, our experiments also demonstrated the ability of the ectonucleotidase cd39 gene delivered by ex vivo intracoronary gene transfer to influence dxr. Recombinant adenoviruses are widely used gene transfer vectors. Article adenovirusmediated p53 gene transfer in advanced nonsmallcell lung cancer. In this study, we report a simple technique that allows an. Adenovirusmediated gene transfer to the respiratory tract. Adenovirusmediated gene transfer to renal glomeruli in.
Adenovirusmediated transfer of the cftr gene to lung of. Gene transfer techniques based on the vectors used the gene transfer techniques can be divided as, nonviral methods. Adenovirus mediated pten gene transfer chrongreen wang, 1aili shiau, shihyao chen, lingling lin,1 minghong tai,2 giashing shieh,3 peyru lin, 1yite yo, 1chehsin lee, shiaomei kuo,4 mingfei liu, iming jou, 1chyunyu yang, pochuan shen,3 hweiling lee,1 and chaoliang wu1 objective. Adenoviral vectors are attractive in that either proliferating or quiescent cells can be transduced, the expression of the introduced gene is evident by 5 hr. Adverse effects of adenovirusmediated gene transfer of human transforming growth factor beta 1 into rabbit knees. The applications of adenoviral vectors in gene delivery have greatly increased in number and efficiency since their initial development. Gene transfer of pdx1 may reprogram tissues other than the pancreas to make insulin and control the abnormally high blood sugar levels in diabetes. Adenovirusmediated gene transfer in mesenchymal stem. Gant tw, thorgeirsson ss, stratfordperricaudet ld, perricaudet m, et al.
Hemophilia b, an xlinked disorder, is ideally suited for gene therapy. Influence of temperature on adenovirus mediated gene transfer. Feasibility of adenovirusmediated hnis gene transfer and. We found that adenovirus mediated gene transfer in mesenchymal stem cells can be significantly enhanced by the cationic polymer polybrene. In this study, we attempted to improve gene delivery efficacy using three different delivery methods to liver grafts with adenoviral vector encoding the lacz marker gene adlacz. Cancer gene therapy by adenovirusmediated gene transfer. A controlled study of adenoviralvectormediated gene. Cancer gene therapy, adenovirus mediated gene transfer, recombinant dna. Pdf adenovirusassociated virus vectormediated gene. Engelhardt, yiping yang, monica zepeda, sara weberpendleton, mariann grossman, and james m. Adenovirusmediated p53 gene transfer in advanced non. Adenoviralmediated gene transfer to fetal pulmonary. In patients with cystic fibrosis, adenoviralvector mediated transfer of the cftr gene did not correct functional defects in nasal epithelium, and local inflammatory responses limited the dose. Paradoxically, following intravascular delivery, car is not used for liver.
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