Publications
| Title | Abstract | Year Filter | PMID(sorted ascending) Filter |
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| in utero aav-mediated gene transfer to rabbit pulmonary epithelium. | in utero intra-amniotic administration of adeno-associated virus (aav) for treatment of cystic fibrosis (cf) has the potential to be an efficient way to target the rapidly dividing undifferentiated cells of the fetal pulmonary epithelium, while simultaneously treating other tissues involved in cf (such as the intestines), but has never before been studied. intra-amniotic administration of 1x10(12) particles of aav-luciferase vector to 110 fetal rabbits at 24-25 days gestation resulted in transge ... | 2001 | 11482982 |
| dose-dependent effects of central leptin gene therapy on genes that regulate body weight and appetite in the hypothalamus. | we have examined the dose-dependent effects and central action of intraventricular administration of a recombinant adeno-associated virus encoding rat leptin (raav-leptin) in suppressing body weight (bw) gain in adult female rats. a low dose of raav-leptin (5x10(10) particles) suppressed weight gain (15%) without changing daily food intake (fi), but a twofold higher dose decreased bw by 30% along with a reduction in daily fi. reduced bw was due to a loss in body adiposity because serum leptin wa ... | 2001 | 11482985 |
| a hypoxia-regulated adeno-associated virus vector for cancer-specific gene therapy. | the presence of hypoxic cells in human brain tumors is an important factor leading to resistance to radiation therapy. however, this physiological difference between normal tissues and tumors also provides the potential for designing cancer-specific gene therapy. we compared the increase of gene expression under anoxia (<0.01% oxygen) produced by 3, 6, and 9 copies of hypoxia-responsive elements (hre) from the erythropoietin gene (epo), which are activated through the transcriptional complex hyp ... | 2001 | 11494119 |
| protamine sulfate enhances the transduction efficiency of recombinant adeno-associated virus-mediated gene delivery. | the purpose of this study was to evaluate glucose responsiveness in hepg2 human hepatoma cells transduced by a recombinant adeno-associated virus (raav) vector containing the insulin gene promoter. and to investigate the effect of protamine sulfate on raav-mediated gene delivery. | 2001 | 11496950 |
| targeted integration of foreign dna into a defined locus on chromosome 19 in k562 cells using aav-derived components. | targeted integration of foreign dna is ideal for gene therapy, particularly when target cells such as hematopoietic cells actively divide and proliferate. adeno-associated virus (aav) has been shown to integrate its genome into a defined locus, aavs1 (19q13.3-qter). the inverted terminal repeat (itr) and rep proteins are responsible for this site-specific integration, and a system has been developed that delivers a gene preferentially into aavs1 by using these components of aav. we examined whet ... | 2001 | 11503961 |
| adeno-associated virus-mediated transfer of endothelial nitric oxide synthase gene inhibits protein synthesis of rat ventricular cardiomyocytes. | we investigated whether nitric oxide (no) synthase gene transfer could attenuate growth of cultured cardiac myocytes. first, we investigated the effects of exogenous no and cgmp analog on protein synthesis of cultured neonatal rat cardiac myocytes. the no donor 3-morpholino-sydnonimine-hydrochloride (sin-1) and 8-bromo-cgmp caused concentration-dependent decreases in phenylephrine-stimulated incorporation of 3h-leucine into cardiac myocytes. we then transferred endothelial constitutive no syntha ... | 2001 | 11504159 |
| altered biology of adeno-associated virus type 2 and human papillomavirus during dual infection of natural host tissue. | adeno-associated virus (aav), a common genital virus, may have a "protective" role against human papillomavirus (hpv)-associated cervical cancer. epidemiological studies indicate a negative correlation between aav infection and the incidence of cervical cancer. in contrast, hpv is positively associated with cervical cancer. to investigate interactions between these two viruses we used the organotypic "raft" culture system. the raft culture system is capable of supporting the complete hpv life cy ... | 2001 | 11504539 |
| reduced prevalence of serum antibodies against adeno-associated virus type 2 in patients with adult t-cell leukaemia lymphoma. | seroepidemiological studies have shown previously that cancer patients are less likely to have antibodies against the tumour suppressive adeno-associated virus (aav) than control groups. to examine the influence of aav infection on the development of adult t-cell leukaemia lymphoma (atll), an endemic disease in southern japan that is caused by infection with the human t-cell leukaemia virus type 1 (htlv-i), the prevalence of serum antibodies to aav type 2 (aav-2) was tested in healthy htlv-i car ... | 2001 | 11505462 |
| gene therapy approach in renal disease in the 21st century. | theoretically, gene therapy has distinct potential to treat renal disease at the most fundamental level. however, the ability to pursue gene therapy has been limited by the availability of an adequate system for gene delivery to the kidney. the present viral vector systems seem to have limitations for clinical use because of uncertainty regarding their toxicity and immunogenicity; however, adenovirus-mediated gene transfer succeeded in gene expression in the kidney. adeno-associated virus has a ... | 2001 | 11509681 |
| characterization of permanent cell lines that contain the aav2 rep-cap genes on an epstein-barr-virus-based episomal plasmid. | recombinant adeno-associated virus (raav) has emerged as a promising gene therapy vector. its development, however, has been hampered by the lack of a readily available efficient production method. we investigated the possibility of establishing permanent cell lines for the production of raav with a new epstein-barr-virus (ebv)-based episomal aav rep-cap plasmid (pcep-rep/cap). hela and 293 cells were stably transfected with plasmids that carry the aav2 rep/cap genes under transcriptional contro ... | 2001 | 11509889 |
| self-complementary recombinant adeno-associated virus (scaav) vectors promote efficient transduction independently of dna synthesis. | adeno-associated virus (aav) vectors package single-stranded genomes and require host-cell synthesis of the complementary strand for transduction. however, when the genome is half wild-type size, aav can package either two copies, or dimeric inverted repeat dna molecules. dimeric, or self-complementary molecules (scaav) should spontaneously reanneal, alleviating the requirement for host-cell dna synthesis. we generated and characterized scaav vectors in order to bypass the rate-limiting step of ... | 2001 | 11509958 |
| variables pertinent to the efficiency of adeno-associated virus (aav) vectors mediated gene transfer to human vascular endothelial cells. | factors influencing adeno-associated virus (aav) - mediated gene transfer to endothelial cells are not fully determined. we tested the variables pertinent to the efficiency of aav-mediated gene transfer to human vascular endothelial cells (huvec) including: (i) kinetics of transduction efficiency of lacz gene to huvec, (ii) the concentration and volume of vector-containing medium, (iii) the period of incubation time of aav vectors with huvec, (iv) the target cell density/proliferation, (v) the d ... | 2001 | 11510757 |
| a novel method using baculovirus-mediated gene transfer for production of recombinant adeno-associated virus vectors. | the baculovirus autographa californica multiple nucleopolyhedrosis virus causes non-productive infection in mammalian cells. recombinant baculovirus therefore has the capability to transfer and express heterologous genes in these cells if a mammalian promoter governs the gene of interest. we have investigated the possibility of using baculovirus as a tool to produce recombinant adeno-associated virus (raav). aav has become increasingly popular as a vector for gene therapy and functional genomics ... | 2001 | 11514714 |
| adeno-associated virus for cancer gene therapy. | 2001 | 11522617 | |
| suppression of choroidal neovascularization by adeno-associated virus vector expressing angiostatin. | to test the efficacy of a recombinant adeno-associated virus (raav) vector that expresses mouse angiostatin in suppressing experimental choroidal neovascularization (cnv) in a rat model. | 2001 | 11527956 |
| virus-mediated killing of cells that lack p53 activity. | a major goal of molecular oncology is to identify means to kill cells lacking p53 function. most current cancer therapy is based on damaging cellular dna by irradiation or chemicals. recent reports support the notion that, in the event of dna damage, the p53 tumour-suppressor protein is able to prevent cell death by sustaining an arrest of the cell cycle at the g2 phase. we report here that adeno-associated virus (aav) selectively induces apoptosis in cells that lack active p53. cells with intac ... | 2001 | 11528480 |
| adeno-associated virus type 2-mediated gene transfer: role of cellular fkbp52 protein in transgene expression. | although adeno-associated virus type 2 (aav) has gained attention as a potentially useful vector for human gene therapy, the transduction efficiencies of aav vectors vary greatly in different cells and tissues in vitro and in vivo. we have documented that a cellular tyrosine phosphoprotein, designated the single-stranded d-sequence-binding protein (ssd-bp), plays a crucial role in aav-mediated transgene expression (k. y. qing, x.-s. wang, d. m. kube, s. ponnazhagan, a. bajpai, and a. srivastava, ... | 2001 | 11533160 |
| adeno-associated virus type 2-mediated transduction of human monocyte-derived dendritic cells: implications for ex vivo immunotherapy. | dendritic cells (dcs) are pivotal antigen-presenting cells for regulating immune responses. a major focus of contemporary vaccine research is the genetic modification of dcs to express antigens or immunomodulatory molecules, utilizing a variety of viral and nonviral vectors, to induce antigen-specific immune responses that ameliorate disease states as diverse as malignancy, infection, autoimmunity, and allergy. the present study has evaluated adeno-associated virus (aav) type 2 as a vector for e ... | 2001 | 11533211 |
| an aav-derived apaf-1 dominant negative inhibitor prevents mptp toxicity as antiapoptotic gene therapy for parkinson's disease. | adeno-associated virus (aav) vector delivery of an apaf-1-dominant negative inhibitor was tested for its antiapoptotic effect on degenerating nigrostriatal neurons in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (mptp) model of parkinson's disease. the wild-type caspase recruitment domain of apaf-1 was used as a dominant negative inhibitor of apaf-1 (raav-apaf-1-dn-egfp). an aav virus vector was used to deliver it into the striatum of c57 black mice, and the animals were treated with mptp. the ... | 2001 | 11535810 |
| molecular pathophysiology and targeted therapeutics for muscular dystrophy. | experimental therapeutics of the muscular dystrophies has made impressive advances on several fronts. adeno-associated virus has emerged as the clear 'vector of choice' for muscle gene delivery, with successful functional rescue of dystrophic muscle in rodent models. correction of the dystrophin gene mutation in a dog model has been reported, and several reports of progress on myogenic stem cell characterization are resurrecting cell transplantation as a possible therapeutic approach. the downst ... | 2001 | 11543874 |
| efficient and selective aav2-mediated gene transfer directed to human vascular endothelial cells. | gene therapy vectors based on adeno-associated virus-2 (aav2) offer considerable promise for human gene therapy. applications for aav vectors are limited to tissues efficiently transduced by the vector due to its natural tropism, which is predominantly skeletal muscle, neurons, and hepatocytes. tropism modification to elevate efficiency and/or selectivity to individual cell types would enhance the scope of aav for disease therapies. the vascular endothelium is implicitly important in cardiovascu ... | 2001 | 11545607 |
| gene therapy for prostate cancer: current status and future prospects. | locally advanced, relapsed and metastatic prostate cancer has a dismal prognosis with conventional therapies offering no more than palliation. in recent years advances achieved in understanding the molecular biology of cancer have afforded clinicians and scientists the opportunity to develop a range of novel genetic therapies for this disease. | 2001 | 11547047 |
| gene therapy of hemophilia. | hemophilia a and b are x-linked bleeding disorders caused by mutations within the factor viii and factor ix genes, respectively. although both disorders can be easily treated by substitution with concentrates of functional factor viii and factor ix, considerable effort has been undertaken to develop a gene therapy for hemophilia in order to improve patients' life quality and reduce high costs of therapy. the principle of gene therapy is the introduction of an intact copy of the factor viii/facto ... | 2001 | 11547364 |
| in vivo hepatic gene therapy. | gene therapy is intended to treat diseases at the gene level by replacing a missense gene with a normal gene or repairing a mutated gene and letting right gene function normally. hepatic gene therapy applies this idea to the areas of inherited and metabolic liver disease, liver cancer, viral hepatitis, or even the systemic diseases, like hemophilia a and b. the strategies of hepatic gene therapy can be divided into two categories: ex vivo and in vivo. the ex vivo method has to harvest the hepato ... | 2001 | 11550406 |
| gene therapy for haemophilia: the end of a 'royal pathology' in the third millennium? | haemophilia is an ideal condition for gene therapy because of its monogenetic character and the fact that it requires only a small amount of the expressed protein to achieve palliation. to date, research in the field of gene therapy for haemophilia has largely relied on retroviruses, adenoviruses and adeno-associated viruses as transfer vectors and the major aims will be to achieve stable longlasting in vivo expression of factors viii or ix (fviii or fix) at therapeutic levels. two clinical tria ... | 2001 | 11554929 |
| long-term expression of a transferred gene in epstein-barr virus transformed human b cells. | delivering a gene into the epstein-barr virus (ebv)-transformed b cells is useful in studying effects of the gene on b-cell functions. however, although people have been able to efficiently transfer genes into and get them expressed in b-lympho blastoid cells for a time probably long enough to kill the cells using vectors harbouring orip, the expression time of the delivered gene is not long enough in order to study the gene function in b cells. to solve this problem, we constructed an adeno-ass ... | 2001 | 11555389 |
| gene therapy in cystic fibrosis. | theoretically, cystic fibrosis transmembrane conductance regulator (cftr) gene replacement during the neonatal period can decrease morbidity and mortality from cystic fibrosis (cf). in vivo gene transfers have been accomplished in cf patients. choice of vector, mode of delivery to airways, translocation of genetic information, and sufficient expression level of the normalized cftr gene are issues that currently are being addressed in the field. the advantages and limitations of viral vectors are ... | 2001 | 11555567 |
| novel cis-acting replication element in the adeno-associated virus type 2 genome is involved in amplification of integrated rep-cap sequences. | this study identifies a region of the adeno-associated virus type 2 (aav-2) rep gene (nucleotides 190 to 540 of wild-type aav-2) as a cis-acting rep-dependent element able to promote the replication of transiently transfected plasmids. this viral element is also shown to be involved in the amplification of integrated sequences in the presence of adenovirus and rep proteins. | 2001 | 11559833 |
| insertional mutagenesis of the adeno-associated virus type 2 (aav2) capsid gene and generation of aav2 vectors targeted to alternative cell-surface receptors. | recombinant adeno-associated virus (aav) vectors are of interest in the context of gene therapy because of their ability to mediate efficient transfer and stable expression of therapeutic genes in a wide variety of tissues. however, aav-mediated gene delivery to specific cell populations is often precluded by the widespread distribution of heparan sulfate proteoglycan (hspg), the primary cellular receptor for the virus. conversely, an increasing number of cell types are being identified that do ... | 2001 | 11560765 |
| gene therapy for hypertension: the preclinical data. | despite several drugs for the treatment of hypertension, there are many patients with poorly controlled high blood pressure. this is partly because all of the available drugs are short-lasting (</=24 hours), have side effects, and are not highly specific. gene therapy offers a possibility of producing longer-lasting effects with precise specificity based on the genetic design. preclinical studies on gene therapy for hypertension have taken 2 approaches. chao et al have performed extensive studie ... | 2001 | 11566928 |
| development of formulations that enhance physical stability of viral vectors for gene therapy. | this study summarizes our initial efforts to address an issue that is critical to the success of any multicenter gene therapy clinical trial - maintenance of vector viability during shipping and storage at remote test sites. we have identified formulation and processing factors that influence stability of viral preparations such as selection of appropriate buffer systems, cryoprotectants, and storage conditions. adenovirus and adeno-associated virus expressing e. coli beta-galactosidase (lacz) w ... | 2001 | 11571564 |
| prevention of systemic clinical disease in mps vii mice following aav-mediated neonatal gene transfer. | for many inborn errors of metabolism, early treatment is critical to prevent long-term developmental sequelae. we have previously shown that systemic treatment of neonatal mucopolysaccharidosis type vii (mps vii) mice with recombinant adeno-associated virus (aav) vectors results in relatively long-term expression of beta-glucuronidase (gusb) in multiple tissues, and a reduction in lysosomal storage. here, we demonstrate that therapeutic levels of enzyme persist for at least 1 year following a si ... | 2001 | 11571565 |
| stable therapeutic serum levels of human alpha-1 antitrypsin (aat) after portal vein injection of recombinant adeno-associated virus (raav) vectors. | previous work from our group showed that recombinant adeno-associated virus (raav) vectors mediated long-term secretion of therapeutic serum levels of human alpha-1 antitrypsin (haat) after a single injection in murine muscle. we hypothesized that hepatocyte transduction could be even more efficient, since these cells represent the natural site of aat production and secretion. to test this hypothesis, raav vectors containing the haat cdna driven by either the human elongation factor 1 alpha prom ... | 2001 | 11571566 |
| quantitative comparison of expression with adeno-associated virus (aav-2) brain-specific gene cassettes. | this study compared a range of mammalian cns expression cassettes in recombinant adeno-associated virus (aav-2) vectors using strong endogenous promoter sequences, with or without a strong post-regulatory element and polyadenylation signal. changes in these elements led to transgene expression varying by over three orders of magnitude. in experiments conducted in primary cell culture and in >100 stereotactically injected rats, we observed highly efficient and stable (>15 months) gene expression ... | 2001 | 11571569 |
| observed incidence of tumorigenesis in long-term rodent studies of raav vectors. | gene therapy using recombinant adeno-associated virus vectors (raav) is generally considered safe. during the course of a study designed to determine the long-term efficacy of raav-mediated gene therapy initiated in newborn mice with the lysosomal storage disease, mucopolysaccharidosis type vii (mpsvii), a significant incidence of hepatocellular carcinomas and angiosarcomas was discovered. a hepatocellular carcinoma was first detected in a 35-week-old mouse and by 72 weeks of age, three out of f ... | 2001 | 11571571 |
| rep-dependent initiation of adeno-associated virus type 2 dna replication by a herpes simplex virus type 1 replication complex in a reconstituted system. | productive infection by adeno-associated virus type 2 (aav) requires coinfection with a helper virus, e.g., adenovirus or herpesviruses. in the case of adenovirus coinfection, the replication machinery of the host cell performs aav dna replication. in contrast, it has been proposed that the herpesvirus replication machinery might replicate aav dna. to investigate this question, we have attempted to reconstitute aav dna replication in vitro using purified herpes simplex virus type 1 (hsv-1) repli ... | 2001 | 11581393 |
| adeno-associated virus-mediated delivery of glial cell line-derived neurotrophic factor protects motor neuron-like cells from apoptosis. | motor neuron disorders including amyotrophic lateral sclerosis may benefit from the induction of neurotrophic factors such as glial cell line-derived neurotrophic factor (gdnf) that are known to be trophic and protective for motor neurons. however, the application of such factors is limited by an inability to successfully target their expression in the nervous system. in this study we investigate the potential of using adeno-associated virus (aav) as a vector for gene delivery into motor neuron- ... | 2001 | 11582516 |
| a phase i study of aerosolized administration of tgaavcf to cystic fibrosis subjects with mild lung disease. | cystic fibrosis (cf) is one of the most common autosomal recessive disorders in north america, leading to significant morbidity and early mortality. the defect in the cystic fibrosis transmembrane conductance regulator protein (cftr) function can be corrected in vitro by gene replacement with a wild-type gene. a phase i, single administration, dose escalation trial was designed and executed to assess safety and delivery of tgaavcf, an adeno-associated virus (aav) vector encoding the human cftr c ... | 2001 | 11589832 |
| uniform gfp-expression in transgenic medaka (oryzias latipes) at the f0 generation. | a green fluorescent protein (gfp) cdna flanked by inverted terminal repeats (itr) of adeno-associated virus was constructed. the construct sharply improved the efficiency and specificity of the transient expression of genes driven by two general promoters (cytomegalovirus and medaka beta-actin) and one muscle-specific promoter (zebrafish alpha-actin) in transgenic medaka. in addition, treatment with itr sequence-containing constructs resulted in a dramatic increase in the number of embryos showi ... | 2001 | 11592710 |
| infection of purified nuclei by adeno-associated virus 2. | adeno-associated virus 2 (aav), a nonpathogenic human parvovirus, requires co-infection with a helper virus for its optimal replication. although aav possesses a broad host range, certain cell types lack the machinery necessary for efficient entry into the cell and intracellular trafficking of aav into the nucleus, where the viral second-strand dna synthesis must occur before gene expression. we have demonstrated that in less-permissive mouse fibroblasts, the virus fails to transport to the nucl ... | 2001 | 11592830 |
| functional effect of adeno-associated virus mediated gene transfer of aromatic l-amino acid decarboxylase into the striatum of 6-ohda-lesioned rats. | in animal models of parkinson's disease, gene transfer of aromatic l-amino acid decarboxylase (aadc) leads to an increase in the capacity of the striatum to decarboxylate exogenous l-dopa. however, the functional effects of enhanced l-dopa to dopamine conversion have not been explored. here, we show that following adeno-associated virus (aav)-aadc transduction, the transgenic aadc is able to decarboxylate exogenous l-dopa more efficiently so that a dose of l-dopa ineffective before gene transfer ... | 2001 | 11592835 |
| a single-step affinity column for purification of serotype-5 based adeno-associated viral vectors. | here we describe a single-step affinity column for purification of vectors based on adeno-associated virus type 5 (aav5). a sialic-acid-rich protein called mucin was covalently attached to sepharose and was found to bind aav5 vectors. elution with high salt efficiently recovered highly active vectors of greater purity than what is achieved with cscl(2) sedimentation. | 2001 | 11592841 |
| development and characterization of an antisense-mediated prepackaging cell line for adeno-associated virus vector production. | one of the limitations of recombinant adeno-associated virus (raav) vector systems for gene therapy applications has been the difficulty in producing the vector in sufficient quantity for adequate evaluation. since the aav rep proteins are cytotoxic, it is not easy to establish stable cell lines that express them constitutively. we describe a novel 293-derived prepackaging cell line which constitutively expresses the antisense rep/cap driven by a loxp-flanked cmv promoter. this cell line was con ... | 2001 | 11594752 |
| protection from experimental endotoxemia by a recombinant adeno-associated virus encoding interleukin 10. | interleukin 10 (il-10) is a homodimeric cytokine that shows considerable clinical promise. adeno-associated virus (aav) vectors appear increasingly useful for in vivo gene-transfer applications. | 2001 | 11601758 |
| gene therapy for muscular dystrophies: current status and future prospects. | since the identification in 1987 of the gene for duchenne muscular dystrophy (dmd), research on the molecular pathogenesis of muscular dystrophy has progressed extensively. in particular, discovery of the dmd gene product, dystrophin, led to the identification of dystrophin-associated proteins and, subsequently, the recognition of other types of muscular dystrophy caused by the defects in each of the sarcoglycan genes. on the other hand, effective therapy for dmd has not yet been established. so ... | 2001 | 11604045 |
| size does matter: overcoming the adeno-associated virus packaging limit. | recombinant adeno-associated virus (raav) vectors mediate long-term gene transfer without any known toxicity. the primary limitation of raav has been the small size of the virion (20 nm), which only permits the packaging of 4.7 kilobases (kb) of exogenous dna, including the promoter, the polyadenylation signal and any other enhancer elements that might be desired. two recent reports (d duan et al: nat med 2000, 6:595-598; z yan et al: proc natl acad sci usa 2000, 97:6716-6721) have exploited a u ... | 2000 | 11667959 |
| dna of adeno-associated virus (aav) in testicular tissue and in abnormal semen samples. | human genital tissues, including spermatozoa, have been found to be frequently infected with the helper-virus dependent parvovirus, adeno-associated virus (aav). | 2001 | 11679515 |
| [possibility and future problems of gene therapy for gastric cancer]. | recently, stage-oriented surgery has been performed for gastric cancer, but a new strategy is necessary for stage iv gastric cancer. the first target of gene therapy for gastric cancer was for stage iv patients with-widespread lymph node metastases and/or peritoneal dissemination. we reported on suicide gene therapy in experimental gastric cancer induced by enng in the dog, and the results showed that in situ gene transfer of a suicide gene (ad. caghsv-tk) followed by prodrug (gcv) treatment may ... | 2001 | 11681005 |
| expression of aav rep proteins in sv40-transformed and untransformed cells: reciprocal interaction with host dna synthesis. | adeno-associated virus (aav) inhibits the induction of host dna synthesis by simian virus 40 (sv40) large-tumour (t) antigen, mediated through aav-encoded 'rep' regulatory proteins. rep proteins are normally synthesized by aav-infected cells only in the presence of adenovirus. however, we observed a low level of rep protein expression in sv40 transformed cells even in the absence of helper virus. in an effort to understand the functional interaction between sv40 t antigen and regulators of aav r ... | 2001 | 11684891 |
| recombinant adeno-associated virus vectors for cystic fibrosis gene therapy. | cystic fibrosis (cf) is an autosomal recessive inherited disorder that affects approximately 30,000 north americans. defects in the cf transmembrane conductance regulator (cftr) gene lead to altered secretions from exocrine glands and the pulmonary airways, to a heightened susceptibility to airway infections with pseudomonas aeruginosa, and to severe airway inflammation. early attempts to develop a genetic therapy for cf have not met with great clinical success, but these efforts have driven the ... | 2001 | 11699895 |
| technology evaluation: anticancer gene therapy, medigene. | medigene is developing recombinant adeno-associated virus (raav) vectors for the potential treatment of cancer, and in particular, melanoma and ovarian cancer [304021]. in june 2001, medigene and its collaborator aventis pharma announced the start of a phase i/ii trial for a vaccine against malignant melanoma [413513]. the therapy works by boosting the patient's immune response. autologous or allogeneic tumor cells are transduced with recombinant adeno-associated virus (raav) vectors, which expr ... | 2001 | 11699897 |
| molecular regulation and biological function of adenovirus early genes: the e4 orfs. | over the past few years there have been a number of interesting advances in our understanding of the functions encoded by the adenovirus early transcription unit 4 (ad e4). a large body of recent data demonstrates that e4 proteins encompass an unexpectedly diverse collection of functions required for efficient viral replication. e4 gene products operate through a complex network of protein interactions with key viral and cellular regulatory components involved in transcription, apoptosis, cell c ... | 2001 | 11707318 |
| adeno-associated virus (aav) site-specific recombination does not require a rep-dependent origin of replication within the aav terminal repeat. | adeno-associated virus (aav) is the only known eukaryotic virus capable of targeted integration in human cells. an aav rep binding element (rbe) and terminal resolution site (trs) identical to the viral terminal repeats required for aav dna replication are located on chromosome (ch) 19. both ch-19 rbe and trs elements have been shown to be essential for viral targeting to this locus. to characterize the role of the aav inverted terminal repeat (itr) cis-acting sequences in targeted integration a ... | 2001 | 11707592 |
| long-term protection of retinal structure but not function using raav.cntf in animal models of retinitis pigmentosa. | the present study aimed to determine whether intravitreal administration of an adeno-associated virus (aav) carrying ciliary neurotrophic factor (cntf) can achieve long-term morphological and physiological rescue of photoreceptors in animal models of retinitis pigmentosa, and whether injection of this virus after degeneration begins is effective in protecting the remaining photoreceptors. we injected raav.cntf.gfp intravitreally in early postnatal prph2(rd2/rd2) (formerly rds/rds) mice and in ad ... | 2001 | 11708883 |
| involvement of cellular double-stranded dna break binding proteins in processing of the recombinant adeno-associated virus genome. | unlike postmitotic tissues in vivo, transduction of cultured cells is poor with recombinant adeno-associated virus (raav). the ability of raav to transduce cells is greatly enhanced by a variety of agents that induce dna damage and is elevated in cells defective in the ataxia telangiectasia gene product (atm), showing increased genomic instability. here we show that dna double-stranded break (dsb) repair pathways are involved in the regulation of raav transduction efficiency. by quantitative chr ... | 2001 | 11711618 |
| widespread gene delivery and structure-specific patterns of expression in the brain after intraventricular injections of neonatal mice with an adeno-associated virus vector. | developing a system for widespread somatic gene transfer in the central nervous system (cns) would be beneficial for understanding the global influence of exogenous genes on animal models. we injected an adeno-associated virus serotype 2 (aav2) vector into the cerebral lateral ventricles at birth and mapped its distribution and transduction pattern from a promoter capable of expression in multiple targets. the injections resulted in structure-specific patterns of expression that were maintained ... | 2001 | 11711628 |
| electron cryo-microscopy and image reconstruction of adeno-associated virus type 2 empty capsids. | adeno-associated virus type 2 empty capsids are composed of three proteins, vp1, vp2 and vp3, which have relative molecular masses of 87, 72 and 62 kda, respectively, and differ in their n-terminal amino acid sequences. they have a likely molar ratio of 1:1:8 and occupy symmetrical equivalent positions in an icosahedrally arranged protein shell. we have investigated empty capsids of adeno-associated virus type 2 by electron cryo-microscopy and icosahedral image reconstruction. the three-dimensio ... | 2001 | 11713191 |
| global cns gene transfer for a childhood neurogenetic enzyme deficiency: canavan disease. | the neurogenetic prototypic disease on which we chose to test our gene therapy strategy is canavan disease (cd). cd is an autosomal recessive leukodystrophy associated with spongiform degeneration of the brain. at present the disease is uniformly fatal in affected probands. cd is characterized by mutations in the aspartoacylase (aspa) gene, resulting in loss of enzyme activity. in this review, recent evidence is summarized on the etiology and possible treatments for cd. in particular, we discuss ... | 1999 | 11713764 |
| gene therapy for hemophilia. | hemophilia is a genetically inherited bleeding disorder caused by a deficiency of the blood clotting factors viii (hemophilia a) or ix (hemophilia b). hemophiliacs suffer prolonged bleeding which can be life threatening and often leads to chronic disabilities. current hemophilia treatment involves infusions of plasma-derived or recombinant clotting factor in response to bleeding crises. prophylactic treatment is not available and current treatments remain problematic. the development of a gene t ... | 1999 | 11713765 |
| technology evaluation: aav-cftr vector, targeted genetics. | targeted genetics is developing a gene therapy product, the aav-cftr vector system, for the treatment of cystic fibrosis (cf). this involves administration of an adeno-associated virus (aav) vector containing cf transmembrane conductance regulator gene (cftr) directly to the lungs of cystic fibrosis patients. the drug has orphan drug status [325713]. medeva acquired the worldwide commercial rights to the therapy in november 1998. medeva expects to file a license application for the therapy, in t ... | 1999 | 11713770 |
| adeno-associated virus vector-mediated il-10 gene delivery prevents type 1 diabetes in nod mice. | the development of spontaneous autoimmune diabetes in nonobese diabetic (nod) mice provides for their use as a model of human type 1 diabetes. to test the feasibility of muscle-directed gene therapy to prevent type 1 diabetes, we developed recombinant adeno-associated virus (raav) vectors containing murine cdnas for immunomodulatory cytokines il-4 or il-10. skeletal muscle transduction of female nod mice with il-10, but not il-4, completely abrogated diabetes. raav-il-10 transduction attenuated ... | 2001 | 11717448 |
| transduction of ovarian cancer cells: a recombinant adeno-associated viral vector compared to an adenoviral vector. | recombinant adeno-associated virus (raav) vectors have emerged as vehicles for gene therapy. in addition, anti-neoplastic properties have been attributed to wild-type aav. to take advantage of both features and to overcome technical problems associated with raav preparation, we developed a production method in which raav particles are amplified in an infectious cycle in the presence of wtaav. this results in a 10(3)-10(4)-fold amplification of raav input particles. raav-gfp particles generated b ... | 2001 | 11720450 |
| hot topics in adeno-associated virus as a gene transfer vector. | adeno-associated virus (aav) is a promising viral vector in treating many kinds of hereditary diseases. the broad host range, low level of immune response, and longevity of gene expression observed with this vector have enabled the initiation of a number of clinical trials using this gene delivery system. another potential benefit of aav vectors is their ability to integrate site-specifically in the presence of rep proteins. however, this virus is not well characterized. to obtain high level, pe ... | 2001 | 11721619 |
| 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 ... | 2001 | 11727501 |
| delivery of novel macromolecular drugs against hiv-1. | the development of new low molecular weight drugs against human immunodeficiency virus type 1 (hiv-1) targets other than reverse transcriptase (rt) and protease, such as the integrase and the envelope glycoprotein, is likely to take many years. macromolecular drugs, including antisense oligonucleotides, ribozymes, rna decoys and transdominant mutant proteins, may be able to interfere with a relatively large number of viral targets, thereby decreasing the likelihood of the emergence of drug-resis ... | 2001 | 11728227 |
| real-time single-molecule imaging of the infection pathway of an adeno-associated virus. | we describe a method, based on single-molecule imaging, that allows the real-time visualization of the infection pathway of single viruses in living cells, each labeled with only one fluorescent dye molecule. the tracking of single viruses removes ensemble averaging. diffusion trajectories with high spatial and time resolution show various modes of motion of adeno-associated viruses (aav) during their infection pathway into living hela cells: (i) consecutive virus touching at the cell surface an ... | 2001 | 11729319 |
| a genetic screen identifies a cellular regulator of adeno-associated virus. | adeno-associated virus type 2 (aav2) is a human parvovirus that has attracted attention as a vector for gene transfer. replication and site-specific integration of the wild-type virus requires binding of the aav2 rep proteins to a cis-regulatory element named the rep recognition sequence (rrs). rrs motifs are found within the cellular aavs1 integration locus, the viral p5 promoter, and the inverted terminal repeats (itrs). here we report the design of a genetic screen based on the yeast one-hybr ... | 2001 | 11734633 |
| immune evasion by muscle-specific gene expression in dystrophic muscle. | muscle tissue from duchenne muscular dystrophy patients and the dmd(mdx/mdx) (hereafter referred to as mdx) mouse is characterized by an abundance of necrotic myofibers and infiltrating macrophages. both features may provide additional stimulus to the immune response directed against novel antigens, such as those delivered by gene therapy vectors. it has previously been shown that the immune evasion achieved by adeno-associated virus in healthy muscle fails in one model of muscular dystrophy. he ... | 2001 | 11735336 |
| immediate and long-term safety of recombinant adeno-associated virus injection into the nonhuman primate muscle. | previous studies on distribution and toxicity of viral vectors administered in monkeys indicated that the nonhuman primate model has a reasonable predictive value for clinical applications. in this study, eight macaques were injected intramuscularly with recombinant adeno-associated virus (raav) at doses similar to those administered to hemophilia b patients, and followed to analyze the dissemination and shedding in biological samples and long-term persistence in distant organs. following raav d ... | 2001 | 11735340 |
| lack of germline transmission of vector sequences following systemic administration of recombinant aav-2 vector in males. | a potential consequence of systemic administration of viral vectors is the inadvertent introduction of foreign dna into recipient germ cells. to evaluate the safety of in vivo recombinant adeno-associated virus (raav) mediated gene transfer approaches for hemophilia b, we explored the risk of germline transmission of vector sequences following intramuscular (im) injection of raav in four species of male animals (mouse, rat, rabbit and dog). in vector biodistribution studies in mice and rats, the ... | 2001 | 11735343 |
| glial cell line derived neurotrophic factor delays photoreceptor degeneration in a transgenic rat model of retinitis pigmentosa. | we designed experiments to evaluate the therapeutic potential of glial cell line derived neurotrophic factor (gdnf) to rescue photoreceptors from genetically determined cell death. gene transfer of the neurotrophic factor to the retina was achieved via a recombinant adeno-associated virus (raav) vector containing the chicken beta-actin promoter/immediate early cytomegalovirus enhancer (cba) driving the human gdnf gene. we delivered aav-cba-gdnf to the retinas of an animal model of retinitis pigm ... | 2001 | 11735347 |
| adeno-associated virus seropositivity and hpv-induced cervical cancer in spain and colombia. | extensive experimental and limited epidemiologic data suggest that adeno-associated viruses (aav) can have antioncogenic activity and may be protective factors for the development of cervical cancer. to examine the association between aav-2 igg antibodies and cervical neoplasia in spain and colombia, we tested for aav-2 antibodies using an elisa assay for 109 women with invasive cervical cancer, 100 population-based controls age-matched to the invasive cases, 77 women with carcinoma in situ (cin ... | 2001 | 11745438 |
| exchange of surface proteins impacts on viral vector cellular specificity and transduction characteristics: the retina as a model. | recombinant vectors based on adeno-associated virus (aav) or human immunodeficiency 1 (lentivirus) are promising tools for long term in vivo gene delivery. their design allows the exchange of capsids or envelopes, respectively, theoretically providing the opportunity to transduce a range of cell types. we constructed aav vectors encoding enhanced green fluorescent protein (egfp) within an aav serotype 2 (aav2) genome contained in an aav2, five or one capsid (called aav2/2, aav2/5 and aav2/1, res ... | 2001 | 11751689 |
| cross-packaging of a single adeno-associated virus (aav) type 2 vector genome into multiple aav serotypes enables transduction with broad specificity. | the serotypes of adeno-associated virus (aav) have the potential to become important resources for clinical gene therapy. in an effort to compare the role of serotype-specific virion shells on vector transduction, we cloned each of the serotype capsid coding domains into a common vector backbone containing aav type 2 replication genes. this strategy allowed the packaging of aav2 inverted terminal repeat vectors into each serotype-specific virions. each of these helper plasmids (pxr1 through pxr5 ... | 2002 | 11752169 |
| efficient generation of cytotoxic t lymphocytes against cervical cancer cells by adeno-associated virus/human papillomavirus type 16 e7 antigen gene transduction into dendritic cells. | adeno-associated virus (aav) is able to efficiently deliver a cytokine gene into dendritic cells (dc). improvements in t cell priming by dc might be effected by the delivery of antigen genes into dc, resulting in continuous protein expression, as most proteins have short half-lives. in this study, a recombinant aav vector containing the human papillomavirus (hpv)-16 e7 gene was used to pulse/infect dc and compared to the pulsing of dc by the lipofection of bacterially produced e7 protein. pulsin ... | 2002 | 11754001 |
| adeno-associated virus type 2 rep78 inhibition of pka and prkx: fine mapping and analysis of mechanism. | hormones and neurotransmitters utilize cyclic amp (camp) as a second messenger in signal transduction pathways to regulate cell growth and division, differentiation, gene expression, and metabolism. adeno-associated virus type 2 (aav-2) nonstructural protein rep78 inhibits members of the camp signal transduction pathway, the protein kinases pka and prkx. we mapped the kinase binding and inhibition domain of rep78 for prkx to amino acids (aa) 526 to 561 and that for pka to aa 526 to 621. these po ... | 2002 | 11773379 |
| a high-capacity, capsid-modified hybrid adenovirus/adeno-associated virus vector for stable transduction of human hematopoietic cells. | to achieve stable gene transfer into human hematopoietic cells, we constructed a new vector, deltaad5/35.aav. this vector has a chimeric capsid containing adenovirus type 35 fibers, which conferred efficient infection of human hematopoietic cells. the deltaad5/35.aav vector genome is deleted for all viral genes, allowing for infection without virus-associated toxicity. to generate high-capacity deltaad5/35.aav vectors, we employed a new technique based on recombination between two first-generati ... | 2002 | 11773389 |
| rapid induction of cytotoxic t-cell response against cervical cancer cells by human papillomavirus type 16 e6 antigen gene delivery into human dendritic cells by an adeno-associated virus vector. | we have shown that the pulsing of dendritic cells (dcs) with human papillomavirus type 16 (hpv-16) antigen proteins by lipofection stimulates class i-restricted cytotoxic t lymphocyte (ctl) response against primary cervical cancer cells. also, we have shown that adeno-associated virus (aav) was able to effectively deliver a cytokine gene into dcs. it has been our hypothesis that the delivery of antigen genes into dcs, resulting in endogenous and continuous antigen protein expression, may result ... | 2001 | 11781657 |
| viral-mediated gene transfer to mouse primary neural progenitor cells. | neural progenitor cells may provide for cell replacement or gene delivery vehicles in neurodegen-erative disease therapies. the expression of therapeutic proteins by neural progenitors would be enhanced by viral-mediated gene transfer, but the effects of several common recombinant viruses on primary progenitor cell populations have not been tested. to address this issue, we cultured cells from embryonic day 16-18 mouse brain in serum-free medium containing epidermal growth factor or basic fibrob ... | 2002 | 11786041 |
| neurological correction of lysosomal storage in a mucopolysaccharidosis iiib mouse model by adeno-associated virus-mediated gene delivery. | mucopolysaccharidosis (mps) iiib is characterized by mild somatic features and severe neurological diseases leading to premature death. no definite treatment is available for mps iiib patients. we constructed two recombinant adeno-associated virus (raav) vectors containing the human alpha-n-acetylglucosaminidase (naglu) cdna driven by either a cmv or a neuron-specific enolase (nse) promoter. in vitro, these raav vectors mediated efficient expression of recombinant naglu in human mps iiib fibrobl ... | 2002 | 11786044 |
| targeted retrograde gene delivery for neuronal protection. | the cellular heterogeneity and complex circuitry of the central nervous system make it difficult to achieve precise delivery of experimental and therapeutic agents. we report here an in vivo retrograde gene delivery strategy to target mature projection neurons using adeno-associated virus, a vector with low toxicity and the capacity for long-term gene expression. viral delivery to axon terminal fields in the hippocampus and striatum resulted in viral internalization, retrograde transport, and tr ... | 2002 | 11786045 |
| adeno-associated virus vector-mediated triple gene transfer of dopamine synthetic enzymes. | to explore triple gene transfer of dopamine synthetic enzymes with separate adeno-associated virus (aav) vectors. | 2001 | 11793852 |
| [construction of a hepatoma-targeting vector of adeno-associated virus containing human alpha-fetoprotein promoter and wild p53 gene in gene therapy of liver cancer]. | to construct plasmids that express target genes in hepatoma cell line using adeno-associated virus (aav) vectors containing human afp promoter. | 2000 | 11798803 |
| feasibility of generating adeno-associated virus packaging cell lines containing inducible adenovirus helper genes. | the adeno-associated virus (aav) vector system is based on nonpathogenic and helper-virus-dependent parvoviruses. the vector system offers safe, efficient, and long-term in vivo gene transfer in numerous tissues. clinical trials using aav vectors have demonstrated vector safety as well as efficiency. the increasing interest in the use of aav for clinical studies demands large quantities of vectors and hence a need for improvement in vector production. the commonly used transient-transfection met ... | 2002 | 11799185 |
| chromosomal effects of adeno-associated virus vector integration. | adeno-associated virus (aav) vectors are currently being used in several clinical gene-therapy trials (see the nih oba human gene transfer clinical trials database); however, little is known about the chromosomal effects of vector integration. here we report that integrated vector proviruses are associated with chromosomal deletions and other rearrangements and are frequently located on chromosome 19 (although not at the wildtype aav integration site). | 2002 | 11799395 |
| [retinal neuronal cell death: molecular mechanism and neuroprotection]. | in retinitis pigmentosa, retinal detachment, age-related macular degeneration, and glaucoma, retinal neuronal cells are damaged by a common mechanism, apoptosis. because apoptosis is an active process that requires de novo expression of a "death message", this process can be controlled by inhibiting the expression of the "death message". we first studied whether a retinal ischemia-reperfusion model can be used as a model for retinal neuronal apoptosis. in the retinal ischemia-reperfusion injurie ... | 2001 | 11802459 |
| rescue of hereditary form of dilated cardiomyopathy by raav-mediated somatic gene therapy: amelioration of morphological findings, sarcolemmal permeability, cardiac performances, and the prognosis of to-2 hamsters. | the hereditary form comprises approximately 1/5 of patients with dilated cardiomyopathy (dcm) and is a major cause of advanced heart failure. medical and socioeconomic settings require novel treatments other than cardiac transplantation. to-2 strain hamsters with congenital dcm show similar clinical and genetic backgrounds to human cases that have defects in the delta-sarcoglycan (delta-sg) gene. to examine the long-term in vivo supplement of normal delta-sg gene driven by cytomegalovirus promot ... | 2002 | 11805334 |
| enhancement of cisplatin-induced apoptosis by infection with adeno-associated virus type 2. | the non-pathogenic human adeno-associated virus, aav, has been shown to sensitize human cancer cells and experimental tumors towards the action of chemotherapeutic agents such as cisplatin. since chemotherapeutic drugs mainly involve the induction of apoptosis, we investigated whether 1 possible mechanism of aav-mediated sensitization of human tumor cells may result from an enhancement of cisplatin-induced apoptosis. in hela and a549 cells, infection with aav type 2 (aav-2) increased cisplatin-i ... | 2002 | 11807802 |
| recombinant adeno-associated virus serotype 2 vectors mediate stable interleukin 10 secretion from salivary glands into the bloodstream. | we have constructed a recombinant adeno-associated virus serotype 2 vector encoding human interleukin 10 (raavhil10). il-10 is a potent antiinflammatory/immune cytokine, which has received growing attention for its therapeutic potential. human il-10 (hil-10) production was virus dose dependent after in vitro infection of hsg cells, a human submandibular gland cell line. the vector-derived hil-10 produced was biologically active, as the medium from raavhil10-infected hsg cells caused a dose-depen ... | 2002 | 11812284 |
| gene therapy strategy for long-term myocardial protection using adeno-associated virus-mediated delivery of heme oxygenase gene. | ischemia and oxidative stress are the leading mechanisms for tissue injury. an ideal strategy for preventive/protective therapy would be to develop an approach that could confer long-term transgene expression and, consequently, tissue protection from repeated ischemia/reperfusion injury with a single administration of a therapeutic gene. in the present study, we used recombinant adeno-associated virus (raav) as a vector for direct delivery of the cytoprotective gene heme oxygenase-1 (ho-1) into ... | 2002 | 11827926 |
| a deviant immune response to viral proteins and transgene product is generated on subretinal administration of adenovirus and adeno-associated virus. | the immune response after ocular exposure to foreign antigens varies substantially from that of a typical systemic response. anterior chamber associated immune deviation (acaid) has been well documented. the immune response of the subretinal space has not been studied in as much detail. here, we characterized the immune response of the subretinal space when it encounters the antigens adv-gfp and aav-gfp (recombinant adenovirus or adeno-associated virus, respectively), each delivering the reporte ... | 2002 | 11829519 |
| ubiquitination of both adeno-associated virus type 2 and 5 capsid proteins affects the transduction efficiency of recombinant vectors. | in the presence of complementing adeno-associated virus type 2 (aav-2) rep proteins, aav-2 genomes can be pseudotyped with the aav-5 capsid to assemble infectious virions. using this pseudotyping strategy, the involvement of the ubiquitin-proteasome system in aav-5 and aav-2 capsid-mediated infections was compared. a recombinant aav-2 (raav-2) proviral luciferase construct was packaged into both aav-2 and aav-5 capsid particles, and transduction efficiencies in a number of cell lines were compar ... | 2002 | 11836382 |
| endocytosis of adeno-associated virus type 5 leads to accumulation of virus particles in the golgi compartment. | among the adeno-associated virus (aav) serotypes which are discussed as vectors for gene therapy aav type 5 (aav5) represents a candidate with unique advantages. to further our knowledge on aav5-specific characteristics, we studied the entry pathway of wild-type virus in hela cells in the absence of helper virus by immunofluorescence and electron microscopy and by western blot analysis. we found virus binding at the apical cell surface, especially at microvilli and, with increasing incubation ti ... | 2002 | 11836412 |
| recent advances in recombinant adeno-associated virus vector production. | adeno-associated virus (aav) is a replication-defective parvovirus that is being developed as a vector for human gene transfer. recombinant aav (raav) vectors are being proposed as a gene transfer vehicle for an array of human diseases. the recent interest in raav has been driven by the unexpected finding that these simple vectors can efficiently transduce a variety of postmitotic cells, resulting in long-lived, robust gene expression. however, a major obstacle to commonplace usage of raav vecto ... | 2002 | 11841606 |
| adeno-associated virus effectively mediates conditional gene modification in the brain. | the cre/loxp system is increasingly showing promise for investigating genes involved in neural function. here, we demonstrate that in vivo modification of genes in the mouse brain can be accomplished in a spatial- and temporal-specific manner by targeted delivery of an adeno-associated virus (aav) encoding a green fluorescent protein/cre recombinase (gfp/cre) fusion protein. by using a reporter mouse, in which cre recombinase activates beta-galactosidase expression, we demonstrate long-term reco ... | 2002 | 11842206 |
| topors, a p53 and topoisomerase i binding protein, interacts with the adeno-associated virus (aav-2) rep78/68 proteins and enhances aav-2 gene expression. | the adeno-associated virus type 2 (aav-2) rep proteins are essential for aav dna replication and regulation of aav gene expression. we have identified a cellular protein interacting with rep78 and rep68 in yeast two-hybrid analysis and in gst pull-down assays. this protein has recently been described as both a p53 (p53bp3) and a topoisomerase i interacting protein (topors). it contains an arginine/serine-rich domain, a ring finger domain and five pest sequences. a minimal sequence sufficient for ... | 2002 | 11842245 |
| inhibition of atherosclerosis in apolipoprotein-e-deficient mice following muscle transduction with adeno-associated virus vectors encoding human apolipoprotein-e. | apolipoprotein e (apoe) is a multifunctional plasma glycoprotein involved in lipoprotein metabolism and a range of cell signalling phenomena. apoe-deficient (apoe(-/-)) mice exhibit severe hypercholesterolaemia and are an excellent model of human atherosclerosis. apoe somatic gene transfer and bone marrow transplantation in apoe(-/-) mice results in reversal of hypercholesterolaemia, inhibition of atherogenesis and regression of atherosclerotic plaque density. replication defective adeno-associa ... | 2002 | 11850719 |
| kinetics of transgene expression in mouse retina following sub-retinal injection of recombinant adeno-associated virus. | using confocal microscopy we have examined in detail the temporal and spatial pattern of green fluorescent protein expression following sub-retinal injection of recombinant adeno-associated virus (raav) in the mouse and have determined the effect of viral titre on the number and type of cells transduced. our results suggest that some transgene expression occurs as early as three days after injection, and that transgene expression occurs beyond the area of retinal detachment. vector titre appears ... | 2002 | 11853771 |
| cftr with a partially deleted r domain corrects the cystic fibrosis chloride transport defect in human airway epithelia in vitro and in mouse nasal mucosa in vivo. | in developing gene therapy for cystic fibrosis (cf) airways disease, a transgene encoding a partially deleted cf transmembrane conductance regulator (cftr) cl- channel could be of value for vectors such as adeno-associated virus that have a limited packaging capacity. earlier studies in heterologous cells indicated that the cftr r (regulatory) domain is predominantly random coil and that parts of the r domain can be deleted without abolishing channel function. therefore, we designed a series of ... | 2002 | 11854474 |
| antitumor effect of an adeno-associated virus vector containing the human interferon-beta gene on experimental intracranial human glioma. | we constructed an adeno-associated virus (aav) vector containing the human interferon-beta (huifn-b ) gene (aav-ifn-beta) and investigated its antitumor effect against human glioma cells (u251-sp) inoculated into the brain of nude mice. prior to this, we examined human glioma cells transduced with aav-ifn-beta using video-enhanced contrast differential interference contrast (vec-dic) microscopy. infection of aav-ifn-beta induced apoptosis and secondary necrosis in human glioma cells. in in vivo ... | 2002 | 11856487 |