This study investigated whether repeated administration of recombinant adeno-associated virus type 5 (rAAV5) to the airways induces inflammatory processes in the lungs of BALB/c-mice, with mechanical and histologic changes. Saline was instilled intratracheally in the control group, and rAAV5-green fluorescence protein (GFP) ...
PubMed
Abstract Intravascular delivery of adeno-associated virus (AAV) vector is commonly used for liver-directed gene therapy. In humans, the high prevalence of neutralizing antibodies to AAV-2 capsid and the wide cross-reactivity with other serotypes hamper vector transduction efficacy. Moreover, the safety of gene-based approaches depends on ...
AbstractRecombinant adeno-associated viral vectors pseudotyped with serotype 5 and 8 capsids (AAV5 and AAV8) have been shown to be efficient gene transfer reagents for the liver. We have produced AAV5 and AAV8 vectors that express mouse short-chain acyl-CoA dehydrogenase ...
PubMed Central
Abstract Recombinant adeno-associated virus 5 (rAAV5) represents a candidate vector with unique advantages for the treatment of hepatic disorders because of its narrow hepatic tropism. Noninvasive in vivo imaging of transgene expression provides an important tool with which to quantify the transduction efficiency, and duration and ...
To clarify whether transduction efficiency and cell type specificity of self-complementary (sc) AAV5 vectors are similar to those of standard, single stranded AAV5 vectors in normal retina, one micro liter of scAAV5-smCBA-GFP vector ...
Lung infections with Pseudomonas aeruginosa and other pathogens in cystic fibrosis (CF) cause progressive airway obstruction and tissue damage, the predominant cause of morbidity and mortality in CF. We investigated whether a recombinant adeno-associated virus type 5 (AAV5) vector expressing murine interleukin (IL)-10 ...
Recombinant adeno-associated virus (AAV) vectors are promising tools for gene therapy. In spinal cord injury where extensive damage occurs, vectors with high diffusion and transduction abilities are required. We compared the diffusion capacity and transduction efficiency of AAV2 and AAV5 vectors using a mouse spinal cord injury model. ...
Untargeted and uncontrolled gene delivery is a major cause of gene therapy failure. This study aimed to define efficient and safe tissue-selective targeted gene therapy approaches for delivering genes into keratocytes of the cornea in vivo using a normal or diseased rabbit model. New Zealand White rabbits, adeno-associated virus serotype 5 (AAV5), and a ...
Since transgenes were first cloned into recombinant adenoviruses almost 30 years ago, a variety of viral vectors have become important tools in genetic research. Viruses adeptly transport genetic material into eukaryotic cells, and replacing all or part of the viral genome with genes of interest or silencing sequences creates a method of gene expression modulation in which the ...
Purpose. We previously showed that subretinal delivery of AAV5 vectors containing murine GC1 cDNA driven by either photoreceptor-specific, (hGRK1) or ubiquitous (smCBA) promoters were capable of restoring cone-mediated function and visual behavior and preserving cone photoreceptors in the guanylatecylase 1 knockout (GC1KO) mouse for three months. Here, we compare therapy ...
Viral vector-mediated gene transfer has emerged as a powerful means to target transgene expression in the central nervous system. Here we characterized the efficacy of serotypes 1 and 5 recombinant adeno-associated virus (rAAV) vectors encoding green fluorescent protein (GFP) after stereotaxic delivery to the neonatal rat and minipig striatum. The ...
BackgroundNeuronal transduction by adeno-associated viral (AAV) vectors has been demonstrated in cortex, brainstem, cerebellum, and sensory ganglia. Intrathecal delivery of AAV serotypes that transduce neurons in dorsal root ganglia (DRG) and spinal cord offers substantial opportunities to 1) further study mechanisms underlying chronic pain, and 2) develop novel gene-based ...
Adeno-associated virus (AAV) provides a promising platform for clinical treatment of neurological disorders owing to its established efficacy and lack of apparent pathogenicity. To use viral vectors in treating neurological disease, however, transduction must occur under neuropathological conditions. Previous studies in rodents have shown that AAV5 more efficiently transduces ...
SummaryTo test whether fast-acting, self complimentary(sc), AAV vector-mediated RPE65 expression prevents cone degeneration and/or restores cone function, two mouse lines were studied: the Rpe65- deficient rd12 mouse and the Rpe65- deficient, rhodpsin null (�i.e. cone function-only�) Rpe65?/?::Rho?/? mouse. ...
Selecting the most efficient recombinant adeno-associated virus (rAAV) serotype for airway gene therapy has been difficult due to cross-specific differences in tropism and immune response between humans and animal models. Chimpanzees�the closest surviving genetic relative of humans�provide a valuable opportunity to select the most effective serotypes for clinical trials in humans. However, ...
To test whether fast-acting, self-complimentary (sc), adeno-associated virus-mediated RPE65 expression prevents cone degeneration and/or restores cone function, we studied two mouse lines: the Rpe65-deficient rd12 mouse and the Rpe65-deficient, rhodopsin null ('that is, cone function-only') Rpe65(-/-)::Rho(-/-) mouse. scAAV5 expressing RPE65 was injected ...
Differences between rodent and human airway cell biology have made it difficult to translate recombinant adeno-associated virus (rAAV)-mediated gene therapies to the lung for cystic fibrosis (CF). As new ferret and pig models for CF become available, knowledge about host cell/vector interactions in these species will become increasingly important for testing potential gene ...
Vectors derived from adeno-associated virus (AAV) are promising candidates for neural cell transduction in vivo because they are nonpathogenic and achieve long-term transduction in the central nervous system. AAV serotype 2 (AAV2) is the most widely used AAV vector in clinical trials based largely on its ability to transduce neural cells in the rodent and ...
From the site: "Vector shoreline data from the National Oceanic and Atmospheric Administration (NOAA) and other federal agencies can be conveniently accessed and ... ...
NBII National Biological Information Infrastructure
The helper-dependent adeno-associated viruses (AAVs) have attracted great interest as vectors for gene therapy. Uptake and intracellular trafficking pathways of AAV are of importance, since they are often rate-limiting steps in infection. Here, we have investigated the entry of AAV type 5 (AAV5) in primary human embryo fibroblasts. At ...
BackgroundThe current method of delivering gene replacement to the posterior segment of the eye involves a three-port pars plana vitrectomy followed by injection of the agent through a 37-gauge cannula, which is potentially wrought with retinal complications. In this paper we investigate the safety and efficacy of delivering adeno-associated viral (AAV) vector to the ...
PurposeWith the increasing number of retinal gene-based therapies and therapeutic constructs, in vitro bioassays characterizing vector transduction efficiency and quality are becoming increasingly important. Currently, in vitro assays quantifying vector transduction efficiency are performed predominantly for non-ocular tissues. A human retinal pigment ...
Globoid cell leukodystrophy (GLD) is a devastating lysosomal storage disease caused by deficiency of the enzyme galactocerebrosidase (GALC). Currently, there is no definite cure for GLD. Several attempts with CNS-directed gene therapy in twitcher mice (a murine model of GLD) demonstrated restricted expression of GALC activity in CNS and failure of therapeutic efficacy in cerebellum and spinal ...
Although recombinant adeno-associated virus (rAAV) has been widely used in lung gene therapy approaches, it remains unclear to what extent commonly used AAV serotypes transduce adult progenitors in the lung. In this study, we evaluated the life span and proliferative capacity of rAAV1-, 2-, and 5-transduced airway cells in mouse lung, using a LacZ-CRE reporter transgenic model and Cre-expressing ...
The development of Alzheimer's disease (AD) is closely connected with cholesterol metabolism. Cholesterol increases the production and deposition of amyloid-? (A?) peptides that result in the formation of amyloid plaques, a hallmark of the pathology. In the brain, cholesterol is synthesized in situ but cannot be degraded nor cross the blood�brain barrier. The major exportable form of brain ...
BackgroundThere is a danger that mass drug administration campaigns may fail to maintain adequate treatment coverage to achieve lymphatic filariasis elimination. Hence, additional measures to suppress transmission might be needed to ensure the success of the Global Program for the Elimination of Lymphatic Filariasis.DiscussionVector control successfully ...
... administration of DCs infected with a rat Her-2-Neu (rH2N) expressing vector (Ad-sig- ... The NT2 rat her-2-neu (rH2N) positive ...
DTIC Science & Technology
Aerosol delivery of nucleic acids to the lungs using viral vectors, polymers, surfactants, or excipients has been described. Compositions for intranasal administration are described that contain nucleic acids without viral or plasmid vectors and with litt...
National Technical Information Service (NTIS)
Glycogen storage disease type II (Pompe disease; MIM 232300) stems from the inherited deficiency of acid-?-glucosidase (GAA; acid maltase; EC 3.2.1.20), which primarily involves cardiac and skeletal muscles. We hypothesized that hydrostatic isolated limb perfusion (ILP) administration of an adeno-associated virus (AAV) vector containing a muscle-specific ...
... of articles on military and naval science, operational warfare ... service publications, Administrative Instructions, Directive-Type Memorandums and ...
... administration of a vector encoding OPG and by genetically-engineering mesenchymal stem cells (MSC) to express OPG for cell based therapy. ...
This is a vector polygon file showing the current land ownership within the administrative boundary of Grant-Kohrs Ranch National Historic Site, Deer ... ...
... vector coverage contains land ownership, administration, and land management class assignments for all of New Mexico relative to NM-GAP procedures. The coverage includes ownership classes for original ... ...
The S/C position vector will be transformed from the M50 system to the geocentric system. ... M50 system to the geocentric system. This is accomplished by ...
NASA Website
that it ia situated AHEdD of the radius-vector relative to comet'6 notion ... The followbg has been marked os the photographs reproduced in the ...
... vector denoting direction of travel of a ... NASA National Aeronautics and Space Administration xxv ... extra-terrestrial sources (for example, the Milky ...
... of Infection The CBER/CDC team demonstrated that a single nasal (mucosal) administration of NP- and M2-expressing rAD vectors (adenovirus genetically modified ...
Center for Biologics Evaluation and Research (CBER)
... vector polygon dataset showing the possible area of construction of visitor and/or administration services at Sand ... ...
This is a vector polygon file showing the current administrative boundary of Grant-Kohrs Ranch National Historic Site, Deer Lodge, Montana....
Adenoviral (Ad) vectors have emerged as a promising gene delivery platform for a variety of therapeutic and vaccine purposes during last two decades. However, the presence of preexisting Ad immunity and the rapid development of Ad vector immunity still pose significant challenges to the clinical use of these vectors. Innate ...
Glycogen storage disease type II (GSD-II; Pompe disease; MIM 232300) stems from the inherited deficiency of acid-?-glucosidase (GAA; acid maltase; EC 3.2.1.20), which primarily involves cardiac and skeletal muscles. We hypothesized that hydrostatic isolated limb perfusion (ILP) administration of an adeno-associated virus (AAV) vector containing a muscle ...
...PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS PATENT TERM RESTORATION Due Diligence Hearing § 124.43 Administrative decision. Within 30 days...
Code of Federal Regulations, 2010
Lentiviral vectors are now in clinical trials for a variety of inherited and acquired disorders. A challenge for moving any viral vector into the clinic is the ability to screen the vector product for the presence of replication-competent virus. Assay development for replication-competent lentivirus (RCL) is particularly challenging ...
Therapy in glycogen storage disease type Ia (GSD Ia), an inherited disorder of carbohydrate metabolism, relies on nutritional support that postpones but fails to prevent long-term complications of GSD Ia. In the canine model for GSD Ia, we evaluated the potential of intravenously delivered adeno-associated virus (AAV) vectors for gene therapy. In three affected canines, liver ...
Immunity to adenoviruses is an important hurdle to be overcome for successful gene therapy. The presence of antibodies to the capsid proteins prevents efficacious adenovirus vector administration in vivo. We tested whether immunity to a particular serotype of adenovirus (Ad5) may be overcome with a vector that encodes the hexon ...
Lentiviral vectors are under intense scrutiny as unique candidate viral vector vaccines against tumor and aggressive pathogens because of their ability to initiate potent and durable specific immune responses. Strategies that alleviate safety concerns will facilitate the clinical developments involving lentiviral vectors. In this ...
We describe the construction of a safe, replication-defective and efficient lentiviral vector suitable for in vivo gene delivery. The reverse transcription of the vector was found to be a rate-limiting step; therefore, promoting the reaction inside the vector particles before delivery significantly enhanced the efficiency of gene ...
In this study, we explored immune responses after intramuscular co-administration of the HIV-1 gp160 Env gene-expressing adenovirus (Ad) vector and modified vaccinia virus Ankara (MVA) vector in a mouse model. Surprisingly, the simultaneous vaccination of the two vaccines, either as a mixture or separately, suppressed responses, when ...
The direct intraparenchymal administration of oncolytic viral vectors by convection-enhanced delivery (CED) represents a promising new treatment strategy for malignant gliomas. However, there is no evidence to suggest that oncolytic viruses as large as herpes simplex virus-1 (HSV-1) can be administered by CED, as this has not been systematically examined ...
Adenoviral vector-mediated gene delivery has been vastly investigated for cystic fibrosis (CF) gene therapy; however, one of its drawbacks is the low efficiency of gene transfer, which is due to basolateral colocalization of viral receptors, immune responses to viral vectors and the presence of a thick mucus layer in the airways of CF patients. Therefore, ...
AbstractRecombinant adeno-associated virus (AAV)-based vectors expressing therapeutic gene products have shown great potential for human gene therapy. One major challenge for translation of promising research to clinical development is the manufacture of sufficient quantities of AAV vectors that meet stringent standards for purity, potency, and safety ...
Muscle represents an attractive target tissue for adeno-associated virus (AAV) vector�mediated gene transfer for hemophilia B (HB). Experience with direct intramuscular (i.m.) administration of AAV vectors in humans showed that the approach is safe but fails to achieve therapeutic efficacy. Here, we present a careful evaluation of ...
We have previously demonstrated that hybrid adeno-associated viral (AAV) vectors bearing nonhomologous inverted terminal repeats (ITRs) enhance directional intermolecular recombination and the efficiency of dual-AAV vector trans-splicing in cultured cells. Using hybrid-ITR vectors carrying two exons of a lacZ minigene, we demonstrate ...
Vectors of trypanosomiasis � tsetse (Glossinidae) in Africa, kissing-bugs (Triatominae) in Latin America � are very different insects but share demographic characteristics that render them highly vulnerable to available control methods. For both, the main operational problems relate to re-invasion of treated areas, and the solution seems to be in very large-scale ...
and were stained with ethidium bromide. Received 22 December 2004; accepted 22 February 2005; doi:10 stained for vector-encoded heat-stable AP as described24 . Safety precautions Vector production, vector administration to mice and harvesting of mouse tissues were performed in laminar-flow biological safety ...
E-print Network
Adeno-associated virus serotype 5 (AAV5) is under development for gene-therapy applications for the treatment of cystic fibrosis. To elucidate the structural features of AAV5 that control its enhanced transduction of the apical surface of airway epithelia compared with other AAV serotypes, X-ray crystallographic studies of the viral capsid have been ...
Energy Citations Database
Items 7 - 12 ... 75 unknown coordinates of fracking stations,. 6 x 121 = 726 unknown elements of orbital state vectors,. 7 x 6 x 121 = 5082 unknown error ...
Measurement geometry requirements involve the use of adequate reference. A single observable .... The prescribed series of measurements will ...... aPn" e, i = 1,2,3 a xi a xi where the vector partial derivatives (a G /ax. ...
The present invention provides a method for inducing an immune response to an adenovirus in a subject which has been pre-exposed to an adenovirus or adenoviral vector. The invention further provides a method for inducing a mucosal immune response to an an...
This data set represents a mosaic of 3 7.5' USGS 1:24K Digital Line Graphs covering the area around Pipestone The files were all scanned and vectorized ... ...
To improve the efficacy of intravenous administration of herpes vectors for metastatic prostate cancer we conducted experiments in the Tramp model system using clinically applicable agents that have been previously shown to transiently inactivate compleme...
This guidance document updates and replaces the 1991 PTC with new information intended to provide manufacturers with current information regarding regulatory concerns for production, quality control testing, and administration of recombinant vectors for g...
...121.20 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION...AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS POSSESSION...TRANSFER OF SELECT AGENTS AND TOXINS § 121.20...
Code of Federal Regulations, 2011
...ORGANISMS AND VECTORS ANIMALS AT LICENSED ESTABLISHMENTS...Applicability. (a) All animals used in licensed...the preparation or testing of biological...the Administrator, animals used in the preparation or testing of biological...
...2011-01-01 false Reprocessing of biological products. 114.18 Section 114...VECTORS PRODUCTION REQUIREMENTS FOR BIOLOGICAL PRODUCTS § 114.18 Reprocessing of biological products. The Administrator...
...2009-01-01 false Reprocessing of biological products. 114.18 Section 114...VECTORS PRODUCTION REQUIREMENTS FOR BIOLOGICAL PRODUCTS § 114.18 Reprocessing of biological products. The Administrator...
... 2011-01-01 false Rebottling of biological products. 114.17 Section 114.17...AND VECTORS PRODUCTION REQUIREMENTS FOR BIOLOGICAL PRODUCTS § 114.17 Rebottling of biological products. The Administrator may...
...2009-01-01 false Rebottling of biological products. 114.17 Section 114...VECTORS PRODUCTION REQUIREMENTS FOR BIOLOGICAL PRODUCTS § 114.17 Rebottling of biological products. The Administrator...
...PRODUCTS; ORGANISMS AND VECTORS PRODUCTION REQUIREMENTS FOR BIOLOGICAL PRODUCTS § 114.1 Applicability. Unless exempted by regulation or otherwise authorized by the Administrator, all biological products prepared, sold, bartered or...
...ORGANISMS AND VECTORS PERMITS FOR BIOLOGICAL PRODUCTS § 104.1 Permit required...Administrator, each permit to import a biological product into the United States shall...regulations in this part. (a) No biological product shall be brought into...
...PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS...establishment qualified to prepare biological products under the Virus-Serum-Toxin Act shall hold an unexpired and...
...INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS LICENSES...qualified to prepare biological products under the Virus-Serum-Toxin Act shall hold an unexpired and unrevoked U.S....
Global climate patterns, such as the El Niño/Southern Oscillation (ENSO, have been shown to have an impact on vector-borne infectious disease outbreaks. In October 2006 the Climate Prediction Center of the National Oceanic and Atmospheric Administration (NOAA/CPC) issued an unscheduled El Niño advis...
Technology Transfer Automated Retrieval System (TEKTRAN)
The ability of transient immunosuppression with a combination of a non-depleting anti-CD4 (NDCD4) antibody and cyclosporine (CyA) to abrogate immune reactivity to both adeno-associated viral vector (AAV) and its transgene product was evaluated. This combination of immunosuppressants resulted in a 20-fold reduction in the resulting anti-AAV8 antibody titres, to levels in ...
Global climate patterns, such as the El Niño/Southern Oscillation (ENSO), have been shown to have an impact on vector-borne infectious disease outbreaks. In October 2006 the Climate Prediction Center of the National Oceanic and Atmospheric Administration (NOAA/CPC) issued an unscheduled El Niño advi...
Repeated administration of morphine increases expression of GluR1 (an AMPA glutamate receptor subunit of morphine. Microinjections of a herpes simplex virus (HSV) vector that causes local overex- pression of GluR1 (HSV-GluR1) into the VTA can enhance the ability of morphine to establish conditioned place
We previously used directed evolution in human airway epithelia to create adeno-associated virus 2.5T (AAV2.5T), a highly infectious chimera of AAV2 and AAV5 with one point mutation (A581T). We hypothesized that the mechanism for its increased infection may be a higher binding affinity to the surface of airway epithelia than its parent AAV5. Here, we show ...
Av[�Aw+�Ar� Am��Ai�eAg 1Ag �Ag...... AG AI@ �AJ� AK�'ALzxAM@OAM AM�hAMx�AK��AIS�AF��AD�hA?�;A=�xA@ >AC|eAG AF��AI -AO ...
Oncolytic (replicating) adenovirus (Ad) vectors are emerging as a promising form of a cancer therapy agent. There has been a need for an appropriate animal model to study oncolytic Ad since human Ad -replication is usually species specific. We have shown that Syrian (golden) hamsters are an appropriate animal model to study human Ad5-based vectors. Syrian ...
We showed previously that a single intranasal vaccination of mice with a recombinant vesicular stomatitis virus (VSV) expressing an influenza virus hemagglutinin (HA) protein provided complete protection from lethal challenge with influenza virus (A. Roberts, E. Kretzschmar, A. S. Perkins, J. Forman, R. Price, L. Buonocore, Y. Kawaoka, and J. K. Rose, J. Virol. 72:4704-4711, 1998). Because some ...
We have recently shown that co-administration of conventional single-stranded adeno-associated virus 2 (ssAAV2) vectors with self-complementary (sc) AAV2-protein phosphatase 5 (PP5) vectors leads to a significant increase in the transduction efficiency of ssAAV2 vectors in human cells in vitro as well as in murine ...
The primary receptor, the coxsackievirus and adenovirus receptor (CAR), and the secondary receptor, ?v integrins, are the tropism determinants of adenovirus (Ad) type 5. Inhibition of the interaction of both the fiber with CAR and the penton base with the ?v integrin appears to be crucial to the development of targeted Ad vectors, which specifically transduce a given cell ...
Glycogen storage disease type II (GSD-II; Pompe disease) causes death in infancy from cardiorespiratory failure. The underlying deficiency of acid alpha-glucosidase (GAA; acid maltase) can be corrected by liver-targeted gene therapy in GSD-II, if secretion of GAA is accompanied by receptor-mediated uptake in cardiac and skeletal muscle. An adeno-associated virus (AAV) vector ...
Protective immunity against avian influenza virus was elicited in chickens by single-dose in ovo vaccination with a non-replicating human adenovirus vector encoding an H5N9 avian influenza virus hemagglutinin. Vaccinated chickens were protected against both H5N1 (89% hemagglutinin homology; 68% protection) and H5N2 (94% hemagglutinin homology; 100% protection) highly ...
Alzheimer's disease is characterized by progressive loss of cognitive function due to amyloid-l (Al) deposits in the central nervous system. Based on the amyloid cascade theory, many reports indicated that immunotherapy is effective for the treatment of Alzheimer's disease. We developed a mucosal immunotherapy for Alzheimer's disease via oral vaccine with recombinant adeno-associated virus (AAV) ...
In order to define the scope of vector control as a component of malaria control in the WHO African Region, examples of recent experiences with different vector control methods in this region are reviewed. Residual house spraying applied alone or in combination with mass drug administration has failed to interrupt malaria transmission ...
Viral vectors are considered as one of the major means for the induction of strong immune responses against recombinant antigens by genetic immunization. Among these, lentiviral vectors are particularly attractive vehicles, as they can infect a wide variety of cells and can transduce replicating as well as non-replicating cells. We have engineered VRX1023, ...
